PMID- 1343470
TI  - Laparoscopic surgery with carbon dioxide insufflation causes respiratory
      acidosis.
AB  - This study analyzes the changes in cardiopulmonary parameters of patients
      undergoing laparoscopic cholecystectomy. Six healthy females with normal
      preoperative cardiopulmonary status were selected for laparoscopic surgery using
      the same criteria as for traditional cholecystectomy. Respiratory and
      cardiovascular parameters were collected and compared prior to peritoneal
      insufflation and just before desufflation. Patients experienced significant
      elevations of arterial and end-tidal CO2, accompanied by decreased pH.
      Bicarbonate concentration, blood pressure and pulse rate remained constant. Based
      on these results, and on our laboratory investigations, we have introduced helium
      as an alternate agent for insufflation, and present the data from the first two
      patients so managed. No change was observed in EtCO2, PaCO2 or pH in either of
      these two patients during the course of surgery. We conclude that hypercarbia
      occurs in those undergoing laparoscopic cholecystectomy with CO2 insufflation.
      This acidosis requires compensation by increased minute ventilation to prevent
      decline in pH. In our initial experience, helium did not produce these changes,
      and therefore merits further investigation as an alternate agent for abdominal
      insufflation.

PMID- 1343471
TI  - Comparison between transabdominal and transvaginal ultrasound in the evaluation
      of a multiple follicular growth.
AB  - The aim of this work is to compare transabdominal and transvaginal ultrasound
      measurement of ovarian size and follicular number and diameter during cycles of
      ovulation induction for assisted reproduction technologies. We included in our
      study fourty patients undergoing a controlled ovarian stimulation: the ultrasound
      monitoring of multiple follicular growth was performed by the same operator, with
      both transabdominal and transvaginal route, during the follicular phase of the
      cycle, until the day of human chorionic gonadotrophin (hCG) administration; in
      ten women was compared transabdominal and transvaginal evaluation of total number
      of recruited follicles > 5 mm in size on day -4, on day -2 and on the hCG
      administration day (day 0); moreover in all the patients transabdominal and
      transvaginal measurement of the mean follicular diameter of leading follicle and
      the mean ovarian diameters on hCG injection day was compared.

PMID- 1343472
TI  - CA-125 monitored therapy with GnRH analogue of pelvic endometriosis.
AB  - Thirteen patients affected by endometriosis have been treated with GnRH analogue
      Buserelin. CA-125 serum levels have been monitored before, during and after
      treatment. Analysis of data suggests the hypothesis of an individualized follow
      up by means of repeated assays of CA-125 and their reference to pre and post
      treatment graphs.

PMID- 1343473
TI  - Operative laparoscopy for ovarian pathology.
AB  - In the last few years, the improvements of the operative laparoscopy have led to
      the use of these techniques as an alternative to traditional surgical approaches.
      Ovarian pathology has been more and more treated by a laparoscopic approach. In
      this paper, the risks and complications of the operative laparoscopy in the
      different forms of ovarian pathology.

PMID- 1343474
TI  - Asymptomatic torsion of the pregnant uterus.
AB  - This case report describes a woman who was admitted to the hospital one week
      before term to an elective cesarean section because of two previously cesarean
      sections. Her present pregnancy was uneventful, the CTG on admission was normal.
      During the operation preformed in epidural anesthesia the uterus was found to
      have rotated 180 degrees to the right. It was easily rotated back to its normal
      position before a transversal incision was made in the lower uterine segment. A
      healthy female infant was delivered. Further the authors describes the role of
      ultrasound in making the diagnosis. The list various symptoms and etiologies. The
      authors emphasize the importance of reconstructing the normal anatomy making the
      uterine incision in order not to damage the uterine vessels.

PMID- 1343475
TI  - Operative laparoscopy in assisted reproduction.
AB  - After the introduction of transvaginal ultrasound guided recovery of oocyte, the
      use of laparoscopy in Assisted Reproductive Technology is limited to GIFT and
      ZIFT or TET method and to the selection of patients. In this paper the Authors
      discuss about these methods, the advantages of tubal gametes or embryos transfer
      versus uterine transfer.

PMID- 1343476
TI  - Is it possible to use the hypoosmotic swelling test as criteria for
      "freezeability" of human semen in an AID program?
AB  - The aim of this study was to determine the possibility of the introduction of
      another parameter--the hypoosmotic swelling test--in the evaluation of the
      freezing potentially of anonymous donor's semen sample to be utilized in an AID
      program. 154 donor semen samples were frozen using classic seminal parameters:
      HOS tests were performed but not utilized as criteria for freezeability. All
      specimens were thawed and another HOS test was performed. All specimens were
      divided into two groups on the basis of the pre freezing HOS test value--HOS
      tests positive (> or = 55%) and HOS test negative (< 55%)--to verify if it's
      possible to correlate this value to the recovery of a good motility after
      thawing. A further division was performed: HOS tests highly positive (> or =
      70%), HOS positive (60-55%) and HOS tests negative (< 55%) but the authors did
      not find any statistical difference. As concerns the clinical evaluation, were
      considered the last 15 pregnancies achieved with 11 samples out of 22 utilized.
      There was not any statistical difference. The data could seem to confirm the
      hypothesis that it is not possible to utilize the HOS test as a predictive value
      of "freezeability" of human semen sample.

PMID- 1343478
TI  - [Therapeutic role of an eating disorders unit of the Psychiatric and Neurologic
      Clinic].

PMID- 1343477
TI  - Document of the SIFES (Italy Society for the study of Fertility and Sterility)
      Ethical Commission.

PMID- 1343479
TI  - [Psychology and sexology in the general hospital].

PMID- 1343480
TI  - [Rhythm of time and care. Current aspects of the social center and therapeutic
      groups in the hospital].

PMID- 1343481
TI  - [Psychodrama, 4 years experience in a day care unit with limited stay].

PMID- 1343482
TI  - [Therapeutic clay group and a patient: transformation of an anorexia nervosa
      patient].

PMID- 1343483
TI  - [Therapeutic work: evaluation of possibilities for social reintegration].

PMID- 1343484
TI  - [Home visit in the child-adolescent psychiatric sector: modalities and valid
      conditions].

PMID- 1343485
TI  - [Treatment center staff and the children referred by DDASS for specialized foster
      home care].
AB  - Many children placed in foster families chosen by the local administrative
      authorities need an intensive and complex treatment, which would well justify
      their case being handled by the Specialized Psychiatric Unit responsible for a
      number of selected foster families. The foster family, which is often chosen
      hurriedly, is generally unprepared to deal with the child's psychological
      problems. Moreover, the child's links with his own family have not always been
      maintained. Soon social workers and the foster mother will be expecting the local
      Child Psychiatry Outpatient Unit to provide them with massive aid, which this
      unit is not properly equipped to give. It happens frequently that members of this
      team will have to face particular counter-transfer difficulties. However certain
      aspects of this medical structure are helpful for the treatment of these
      children: the Child Psychiatry Unit offer specific facilities, like therapeutic
      groups, and as the members of its team have no part in the factual decisions
      concerning the fate of the child, they feel more neutral and can be considered so
      by the different actors involved, including the child him- or herself. We discuss
      two clinical cases, and then touch upon the fundamental issue involved, that of
      the organizing power of psychiatry in a given environment.

PMID- 1343486
TI  - [Paramedical personnel in psychiatry: specifics of training in a military
      teaching hospital].

PMID- 1343487
TI  - [Primary importance of warm and comforting staff for the very elderly placed in
      psychiatric care].

PMID- 1343488
TI  - [Am I the brother of my guardian?].

PMID- 1343489
TI  - [Paramedical personnel and transitional phenomena in institutional treatment].

PMID- 1343490
TI  - [Presentation of a crisis unit for adolescents and different domains for
      implementing the nursing role].

PMID- 1343491
TI  - [Nursing and paramedical personnel: cooperation or competition with the
      psychiatrist].

PMID- 1343492
TI  - [The nursing team in a closed psychiatric unit].

PMID- 1343493
TI  - [Development of an exercise in community health work by a treatment center team].

PMID- 1343494
TI  - [Activities and therapeutic roles of paramedical personnel. Treatment experience
      of the Psychiatric Service at the Laverne Military Training Hospital].

PMID- 1343495
TI  - [The work of collecting materials of artistic expression from various media].
AB  - Work of collection of productions made in workshops of expression constitute a
      specific need for evaluation in art-therapy. The Mediatised Observation is
      completed by special validated (K-test) and built instruments of description for
      productions from each mediation (paintings, writings, music...) and for observed
      behaviours in situ during therapeutic work of creation. The two benefits are for
      nurses education, and for elaboration of a clinic of aesthetic.

PMID- 1343496
TI  - [Nursing problems in intensive care for psychiatric patients].
AB  - Two cases illustrate psychotherapeutic aspects of surgical intensive cares for
      psychiatric patients. Comparison with their style of expression in art-therapy
      allows a better understanding in their relations with the technical and non human
      environment.

PMID- 1343497
TI  - [Home visits by psychiatric nurses: evaluation of the process, the clientele and
      the results].

PMID- 1343498
TI  - [Hippocratic concept of hysteria].
AB  - The Greek physicians of the fourth century B.C. painstakingly described a number
      of symptoms that they thought were caused by migrations of a restless uterus,
      said "wandering womb". According to this concept, we can use the term "hysteria",
      despite the fact that the noun itself never appears in any of the Hippocratic
      texts. We can determine its origin as being in ancient Egypt from the medical
      writings of the Egyptian papyri. In the same way, the therapy is mainly of
      Egyptian origin, using a combination of recipes to make the moving womb return to
      its proper place in the body cavity. However, we can also identify the
      rationality of the Greeks, in particular as regards mechanical physiopathology.
      Hippocratic authors are closely connected with presocratical physics, and
      manifest a distinct break with magic and religion. Furthermore, they claim that
      hysteria may result from prolonged sexual continence, an opinion which was to
      influence medical history for over two thousand years.

PMID- 1343499
TI  - [Improving one's "look". Images and caricatures of psychiatry].

PMID- 1343500
TI  - [Rape under hypnosis. A healer sentenced].

PMID- 1343501
TI  - [Retrospective study of 935 sessions of electroconvulsive therapy (1989-91)].

PMID- 1343502
TI  - [Kleptomania and pyromania. Apropos of a case].

PMID- 1343503
TI  - [Indications for psychiatric hospitalization in senile dementia].

PMID- 1343504
TI  - [The reliability of expert assessment: comparative study of hospitalized or
      imprisoned patients following criminal behavior].

PMID- 1343505
TI  - [Induction by neuroleptics of certain genes in the central nervous system].
AB  - Prolonged administration of neuroleptic drugs increases the density of dopamine
      D2 receptors in several brain regions. We have recently shown that such treatment
      also raises dopamine D2 receptor mRNA levels in the striatum. To elucidate some
      of the initial events which lead to this upregulation, we studied the acute
      effects of dopamine D2 agonists and antagonists on the expression of c-jun and c
      fos. A single injection I.P. of haloperidol (2 mg/kg) produced a rapid and
      transient increase in c-jun and c-fos mRNA in the rat striatum. This induction
      was specifically blocked by a D2 agonist (1 mg/kg quinelorane). In contrast, by
      itself quinelorane was without effect. These results show that dopamine D2
      receptors inhibit the expression of a set of immediate early genes in the
      striatum, and these may be involved in the up-regulation of D2 mRNA upon
      prolonged neuroleptic treatment.

PMID- 1343506
TI  - [Central dopaminergic receptors and negative symptoms in schizophrenia].

PMID- 1343507
TI  - [Physiopathology of dementia of the Alzheimer type: role of the amyloid beta
      protein].
AB  - Biological research on Alzheimer's disease is expanding quickly, and the
      mechanisms of the disease are better understood today. Progress has been
      specially impressive in the knowledge of the brain lesions (senile plaques,
      neurofibrillary degeneration). It is likely that the beta-amyloid protein, which
      accumulates in the senile plaques plays a major role in the development of the
      brain lesions and, subsequently of the clinical symptoms. The metabolism of the
      precursor of this protein might be abnormal, leading to the beta-amyloid protein
      deposits. Some discrete genetic abnormalities (such as punctate mutations on the
      beta amyloid precursor gene) have been described recently in familial cases of
      the disease. It seems unlikely that such punctate mutations would be responsible
      for the majority of the cases. Therefore it is possible that Alzheimer's disease
      has multiple causes, the genetic factors being only one of them.

PMID- 1343508
TI  - [Alcohol and the serotonin system].
AB  - There is considerable evidence from animal and human studies that serotonin plays
      a role in the modulation of alcohol intake and/or alcohol dependence.
      Biochemical, behavioral and pharmacological studies both in animal and man had
      verified this hypothesis. Central and peripheral levels of serotonin and of its
      metabolite 5-hydroxyindoleacetic acid (5-HIAA) are modified by alcoholisation.
      Moreover, the use of pharmacological drugs modifying specifically serotonin
      transmission decreases ethanol intake. Our own studies suggest that a
      dysfunctioning of serotonin uptake system could be implicated in the individual
      risk of alcohol dependence. Even if other systems, e.g. amino acids, are involved
      in the regulation of alcohol behavior, all data are in favor of a modulation of
      alcohol intake by serotonin transmission.

PMID- 1343509
TI  - [Importance of neurobiologic studies in Alzheimer's disease. The role of growth
      factors].

PMID- 1343510
TI  - [Neuroendocrine disturbances observed in obsessive compulsive disorders].

PMID- 1343511
TI  - [What is biological psychiatry?].

PMID- 1343512
TI  - [Cognitive ergonomics: use in man-machine systems].

PMID- 1343513
TI  - [Psychiatric disorders and diaschisis. Conclusions drawn from brain imaging].

PMID- 1343514
TI  - [Evolution, capabilities and limits of psychopharmacology].
AB  - Evolution of psychopharmacology is discussed from the viewpoint of the growth of
      the number of psychotropic drugs, their use and the rate of scientific reports
      related to them. Power is discussed from the standpoint of economic perspectives,
      although it is not the only aim. On the other hand, the influence of the
      psychopharmacological "boom" on the development of the specialty is analyzed. The
      limits of psychopharmacology achieve their maximum extent when they are combined
      with the study of psychological, social and cultural factors and determinants
      and, hence, to other therapeutic methods.

PMID- 1343515
TI  - [Nonspecific factors and variations in biological parameters studied in
      biological psychiatry].
AB  - Some studies found no connection at all between biological parameters and mental
      illness. There are many reasons for the discrepancies: populations and parameters
      investigated as well as the method used, widely differed. The discrepancies
      observed, could also be partly due to several non-specific factors such as age,
      sex, hormonal status, circadian or circannual variations, and washout period. The
      authors report here some data gathered in the course of a psychobiological
      research program on healthy volunteers. Their results indicate that human
      plateler MAO activity shows an apparent menstrual cycle related variation [3H]
      IMI binding in human platelets shows circadian variations in summer and some
      antidepressant drugs have a residual effect on serotoninergic parameters during
      one month. These studies oblige investigators to be cautious when interpreting
      biological data in psychiatry. Ideally longitudinal studies should be implemented
      at the various stages of mental illness.

PMID- 1343516
TI  - [Importance and limits of statistical methods in psychiatry].
AB  - Clinical reasoning and statistical treatment of psychiatric data interact to
      reduce the risk of random diagnosis and prognostic probabilities. Errors of
      statistical procedures are found in an important amount of papers in the most
      reliable psychiatric journals. Guide-lines for reporting statistics are given
      advising the authors about mistaking statistic application. Unfortunately, on a
      more elementary level, representation of data are often criticizable for they are
      incomplete, or make difficulties of decoding. Harmonization of data
      representation is then desirable. Some remarks are expressed about paucity of
      negative studies in literature.

PMID- 1343517
TI  - [Scientific methodology and psychopharmacology].

PMID- 1343518
TI  - [Strategy of the pharmaceutical industry in the evaluation of a research program
      and plan of development].

PMID- 1343519
TI  - [Animal models in psychiatry].

PMID- 1343520
TI  - [Significance of studies of motor activity in depression].
AB  - Actometry is a technique that enables continuous monitoring of spontaneous motor
      activity. This technique can be applied to the study of depression either by
      studying qualitative motor activity patterns or by measuring quantitative motor
      parameters. We present here the results of a quantitative actometric analysis. 13
      depressive in-patients were evaluated both clinically by depression scales and by
      actometry before and after trimipramine treatment. Correlation analysis was made
      between actometric and clinical rating scores at different moments of the
      treatment. Some actometric parameters appear to be specific indices of depression
      and psychomotor retardation. Future prospects for the use of actometric
      techniques in depression are discussed.

PMID- 1343521
TI  - [The lithium test, test of endogenous criteria].
AB  - The lithium-test (Li-T) requests hospitalisation of the patient, administration
      of Li to obtain a plasma/level of at the lust 0, 8 mEq/l, since the third to the
      eight day. It improve depressions, acute delusions, pseudo-dementias: the field
      of the lithiodependent endogenic diseases as to be enlarged. The Li-T may
      distinguish between this lithiodependence of the other, non-lithiodependent, in
      dysthymic psychotic disorders.

PMID- 1343522
TI  - [Correlations between delayed auditory evoked potentials and clinical evaluation
      of schizophrenic symptoms].
AB  - Late auditory evoked potentials (AEPs) were recorded by the "odd-ball" method in
      20 schizophrenic patients according to DSM III R diagnosis criteria compared with
      30 control subjects matched for sex and age. Patients were on antipsychotic
      medications; mean duration of illness was 3, 55 years. We have also proceeded to
      a clinical quantitative assessment of negative and positive symptoms of
      schizophrenia with Andreasen's rating scales. In the group of patients, we have
      observed a significant lengthening of the latency of N 1, N 2, P 3, N 3 and a
      decreased amplitude of N 1 and P 3. These results are in favour of an impairment
      of cerebral information processing probably localized in the subcortical level.
      Statistically significant correlations have been noticed between the anomalies of
      the last stages of information processing (P 3, N 3) and negative symptoms, more
      particularly affective flattening and attentional impairment. The disturbances of
      the first stages of information processing (P 2) and of automatic information
      processing (N 2) were related to positive symptoms, hallucinations and delusions
      especially. The anomalies of N 2 were also related to the sum of the global
      scores: an attentional impairment could be a main factor in the determinism of
      schizophrenia.

PMID- 1343523
TI  - [Study of 100 patients treated with iproniazid or "the myth of MAO inhibitors"].

PMID- 1343524
TI  - [A case of delusional melancholia: "a variant of loss of psychological self
      activation"?].
AB  - A 62 year-old man presented with melancholia with delusions, possibly resulting
      from lenticular lesion in the left and frontal damages in the right. Atypical
      signs of our observation led us to consider our patient not as suffering of
      affective disorder. We suggest that melancholia could be a consequence of a
      certain type of stereotyped mental activity, and we would compare this
      stereotyped mental activity to mental compulsive activity described in "loss of
      psychic self activation" of D. Laplane. In this perspective our observation would
      be a variant of "Loss of psychic self-activation". Heuristic value of this
      concept is discussed.

PMID- 1343525
TI  - [Depression and functional EEG asymmetry].
AB  - A new quantified EEG index (Alpha Burst Occurrence Variability Index: alpha BVI)
      has been devised in order to characterize sequential variations of alpha bursts
      in EEG. This index makes it possible to quantify slope variations of a cumulative
      graph (periodogram) where the rank of alpha bursts is traced as a function of
      their instant of arrival. Such quantitative analysis was applied to spontaneous
      EEG segments which were recorded in the parieto-occipital regions (P3-Fz and P4
      Fz) during a rest period, in three groups of depressed patients, one being
      characterized by psychomotor retardation (PRM group), another one by an emotional
      blunting (EB group) and a group of impulsive depressed patients (I group). The
      patients were compared to a group of healthy control subjects. In the three
      patient groups, before treatment, it was observed that the right and left alpha
      BVI were significantly lower than those of the control subjects. The right
      hemisphere was involved in all cases, but the left hemisphere was involved only
      in severe cases. In the EB and I groups, two strong "electro-clinical"
      correlations were observed, each one being specific for each hemisphere, one
      relating the reduction of the right alpha BVI to the depressive mood, the other
      relating the reduction of the left alpha BVI to the degree of speech
      ("ideoverbal") retardation. These results emphasize the role of the right
      hemisphere in the probable pathogenesis of depression.

PMID- 1343526
TI  - [Panic attacks and 24-hour ambulatory EEG monitoring].
AB  - A 24 hour ambulatory EEG study performed in a population of 300 non epileptic
      outpatients with an anxious and depressive pathology revealed a high prevalence
      of abnormalities in subjects referred with panic disorder. Two groups of 150
      medication-free patients each have been selected on the base of DSM-III-R = one
      with panic attacks (PA), the other with depressive patients without paroxystic
      anxiety (DS). The results showed respectively = in the PA group 63.2% abnormal,
      19.7% normal and 17.1% dubious records. In the DS group = 74.5% normal, 18.3%
      abnormal and 7.2% dubious records. Epileptiform abnormalities were 4 times more
      frequent in the PA group (80%) than in the DS group (20%). Two nycthemeral peaks
      were found (5-8 pm and 3 hours after awakening). MRI has permitted the discovery
      of abnormal cerebral images in 3 patients of the PA group (cyst of the insula,
      temporal and parietal cryptic angiomas, sequelae of a parietal vasculo-cerebral
      stroke) frequency appearing to be clearly superior to the one resulting from
      recent epidemiologic data. The subclinical character of 2/3 of these
      abnormalities refers beyond epilepsy to their signification in the field of
      emotive and intellectual disturbances. The paradoxal efficiency of tricyclic
      drugs in panic disorder, sets the problem of their eventual antiepileptic action
      at low doses. If recent data on standard EEG in panic disorder is available, we
      did not find any similar study to ours in order to confront our results.

PMID- 1343527
TI  - [Perspectives of interdisciplinary research in psychiatry].

PMID- 1343528
TI  - [Convergence between systemic clinical aspects and current concepts of systems].

PMID- 1343529
TI  - [Comprehensive epistemology aspects of human personality, as a new paradigm in
      psychopathology research].
AB  - To apprehend the integrality of the psycho-pathological problems of the human
      being, the use of a paradigm is necessary. The epistemological paradigm, based on
      the study of the principles which govern any dynamic system, seems very useful.
      Applied to the human being, it raises questions of energy, semantics,
      organization of functions, environments, and it can lead to a better
      comprehension of the psychism. In psycho-pathology, this paradigm puts in
      evidence the innumerable interrelations which intervene at all the levels to
      create disturbances in the functions, inducing troubles of communications with
      the consciousness resulting in diminution or non-function of the latter, type
      psychosis, or in its activation, type neurosis.

PMID- 1343530
TI  - [Anthropology and psychiatry: methodologic problems].

PMID- 1343531
TI  - [Non-verbal clinical psychiatric aspects].
AB  - Mimic, involuntary movements, agitation or immobility, are parts of description,
      comprehension and evaluation of any human behaviour, normal or not: they were
      included in the classic european psychiatries. They almost disappear from the
      actual scales of evaluation, or from the training through scales. It seems
      possible to complete such scales, exclusively verbal, by scales of behaviours
      suicidal attempt being a good instance of such behaviours.

PMID- 1343532
TI  - [Interruption and misunderstanding. Examples of the construction of discourse in
      clinical interviews].
AB  - How do subjects construct shared meaning during an actual exchange? This question
      is treated through the study of dialogical behaviours of three psychiatric
      patients during a clinical interview (Two psychotics and one psychopathic). The
      analysis of their different ways of linking utterances shows difficulties that
      concern the construction of a common discursive ground. These difficulties, that
      can be considered either from a deficitary point of view or from a creative one,
      appear on the repetition of unexpected changes, of communication blocking or of
      inadequate indication of the way utterances mean.

PMID- 1343534
TI  - [A base for building the status of clinical research in psychiatry].

PMID- 1343533
TI  - [Research in psychiatry, conflict between the tragic issue and knowledge modes].

PMID- 1343535
TI  - [The first name of the vicarious child].

PMID- 1343536
TI  - [Narcolepsy and the psychiatric tableau. A specific form of narcolepsy?].
AB  - Narcolepsy is a well-known hypersomnia. Nevertheless narcolepsy in which the
      hallucinatory component is unusually prominent may lead to a false diagnosis of
      schizophrenia syndrome. This aspect is illustrated by the case of Miss B. who
      appears like a psychotic patient without dissociation syndrome and with a
      hysterical personality. Are the narcoleptics with psychiatric disorders a
      peculiar sub-type of narcolepsy? Fourty-five percent of our eleven narcoleptics
      patients have an associated psychiatric disorder. Most of them are depressive.
      Surprisingly fourty percent of our patients are non-DR2 at the Human Leucocyte
      Antigen typing. Furthermore seventy five percent of them have an associated
      psychiatric disorder. This would mean a peculiar sub-type of narcolepsy.

PMID- 1343537
TI  - [Anthropology and delusional disorders: Antilles and Cameroon discourse].
AB  - We are sometimes compare, in our practice, with treatment of patients coming from
      beyond the seas (like Guadeloup, West Indies). The psychologic characters are
      extremely confusing because the symptoms are polymorphs in the same patient, some
      character of hysteric, delirious and depressive registers, and also there is a
      cultural color changing the deep signification of symptoms presented to the
      doctor. The diagnostic research are not unusual face our proper culture and with
      inadequation of the classic diagnostical characters. The treatment's antilly
      patients mind the attirance for the exotic and the unknown phobies captivate and
      question our proper subjectivity.

PMID- 1343538
TI  - [A new approach to psychosis. Is psychosis a disorder of mental reality?].
AB  - World's knowledge is but imperfectly intelligible to thinking beings by binding
      Possible with Reality of the experience meaning what resists them (matter or
      form) as sensible organ, while time perception remains out of feeling. Although
      the Reason seeks coherence in its seizing of the World, only consisting in
      experiences, yet the various experiences are not ordered a-priori towards
      coherence as an aim. The Reason ascribes the experiences to be pre-classified
      according to three modes: Continuity-Successiveness-Reversibility, connecting a
      physical fact (temporarily) to a thought fact (classifying). This motion towards
      a coherent understanding of the World proceeds by leaps over representations in
      three ways: 1-induction without requirement nor warranties. 2-analogical
      interpretation in which the middle term offers a slight validity. 3-demonstration
      where experiences get authentified but needs term successiveness undoubtedly
      marked in time. In case of a time mark deficiency, the demonstrative way gets out
      of warranty. The subject loses his free choice between Possible and Reality,
      causing psychosis. Yet the thought, getting improper to appreciate and correct
      the less gap between itself and experiences becomes else: thence, filtered by
      matter, it responds to chemotherapeutic strategies. The various symptoms in
      Psychosis can be brought to a selective deficit of the experience's pre
      classifying such as: -lack of "reversibility" troubling the course of thoughts,
      causing hermetism etc... -lack of "continuity" making easier experience
      materiality causing hallucinations. -defect of "successiveness" supporting the
      Possible for loss of the Reality causing delusion conviction.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1343539
TI  - [Experience of solitude in borderline personality psychopathology].

PMID- 1343540
TI  - [Are co-therapies indicated in schizophrenia?].
AB  - The "cotherapies" which are often indicated for neurotic patients, see to be more
      difficult to be used for psychotic patients. What are the advantages of such
      treatments for schizophrenic patients? Using case stories we are going to try to
      know the good prognosis factors for the success of these cotherapeutical
      treatment. Our situation is particular: one of us is a full-time, the other is
      psychoanalyst and a consultant-psychiatrist in the same hospital.

PMID- 1343541
TI  - [Apropos of psychiatric classification: different requirements for clinical
      practice and research].

PMID- 1343542
TI  - [The British and French systems of classification and psychiatric disorders].
AB  - We compare the french diagnostic system with that used in Great-Britain. The
      criteria are very similar except in the case of the non-affective functional
      psychoses. The French divide these into acute and chronic. Bouffee delirante, the
      prototype of the acute functional psychoses, is not diagnosed in Great-Britain.
      The British divide these psychoses into schizophrenic and non-schizophrenic
      disorders, particularly using Schneiderian criteria for the diagnosis of
      schizophrenia. Curiously, it is precisely these criteria, referred to as
      "automatisme mental" (Clerambault) which are used in France in order to diagnose
      the "chronic hallucinatory psychoses". This is a diagnosis which is unknown in
      Great-Britain, and which is in France classed firmly among the non-schizophrenic
      psychoses, truly a paradoxical situation.

PMID- 1343543
TI  - [Classification systems and diagnostic coherence in clinical psychopharmacology].

PMID- 1343544
TI  - [Clinical research on violence].
AB  - Violence and agitation are two different behaviors however not always
      differentiated. There are not only physical violence but also moral violence such
      as erotomania eventually more dangerous. There is no clear definition of
      violence. Research should be improved. Today there is an increase of different
      types of violence, such as self-inflicted violence as in suicidal behavior,
      rather frequently associated with alcoholism. Clinical experience is given from
      l'Infirmerie Psychiatrique, a forensic psychiatric emergency department.

PMID- 1343545
TI  - [Research in schizophrenia: necessity to include patients of multiple diagnostic
      systems].
AB  - The discrepancies of studies on symptomatology and treatment of schizophrenia
      could be related to the selection of different patients diagnosed by one
      diagnostic system, different from a study to another. Therefore, we tested
      whether 14 diagnostic systems could include 51 patients differently as regard to
      the intensity of positive, negative or depressive symptomatology and to the phase
      of illness. The distribution of the patients in different sets of diagnosis has
      been carried out by a computer program and the symptomatology has been evaluated
      with PANSS and MADRS. Some diagnostic criteria like DSMIII-R, Langfeldt, Taylor,
      ICD 9 include negative and depressive patients preferentially. Others systems
      like Berner, Catego, ICD 9, New-Haven, Schneider, include more patients with
      acute than residual symptoms. These results show the importance of the choice of
      one or more diagnostic criteria depending on the aim of the study.

PMID- 1343546
TI  - [Stress and depression].
AB  - Can modern life foster more depression life? Neuroendocrine, epidemiological and
      even immunological approaches allow us to suppose a passage between stress and
      depression, far beyond the archetype of exhaustion depression (break down
      syndrome).

PMID- 1343547
TI  - [Reflections apropos of standardized interviews].

PMID- 1343548
TI  - [Foundations and methods for future chronopsychiatry].

PMID- 1343549
TI  - [Alterations of arousal in some psychopathologic states].
AB  - An electro-behaviour dissociation was described, at first by animals next about
      the man, in experiment testing and in the drug addictions. This non concordance
      appear as lesser if it is be considered not only the sleeping waves but also all
      the electrical signs of the vigil state: non-existent, fluctuating, limited in
      topography, behind the stimulation, incomplete or emphasized. In this view we
      study some pathological states: narcotic and alcoholic addictions, confusion and
      pre-senile illness. Sometimes it is the abnormal sleep (coma or amazement) which
      alter the vigil state: absent, decreased, etc. Sometimes the vigilance is
      "numbed", the behaviour and the recording are those of lethargy. Sometimes also,
      the drowsiness has insomnia characteristics, associating a deep sleep loss, a
      reactivity to stimulations at once emphasized and undiscriminated, and
      "strangeness" insurmontable for the consciousness (perplexity, delusions,
      nightmare and level anomalies).

PMID- 1343550
TI  - [Language of the clinic].
AB  - In this report, the authors examine the problems of specific languages in
      medical, psychiatric and psychologic practice. They emphasize a specific
      epistemological view to be able to capture the distinction between clinical
      tongue, common parlance and specific languages.

PMID- 1343551
TI  - [Proposition of a new concept: "sequence of communication"].
AB  - What we suggest as a concept is "The sequence of communication" which is
      accessible to experimenting excluding the concept of "black box". The sequence of
      communication point out the print of sensations their coding, and a scheme of
      action as well. This concept enables us to treat information in its unicity
      taking into account its reception, its analysis and its emission all together.
      It's a way to avoid the differentiation, or even the clash between "what is
      felt", "what is said" and "what is acted". From the semiological point of view
      this approach allows us to stress an analogy between symptoms, which until now
      have been listed in different pathologies. From the methodological point of view,
      some hypothesis of work concerning anguish are drawn. On the therapeutic point of
      view, taking into account the "affects" in a logical context, enables the patient
      to master his own behaviour.

PMID- 1343552
TI  - [Elaboration, perlaboration, in the course of antidepressant chemotherapy].
AB  - From the results of an 8 years naturalistic and pragmatical study in a Care Unit
      for Patients with Dysthymic Disorders at Hotel-Dieu-Pont-L'Abbe (France), the
      author points out that there is during long term antidepressive therapies a
      facilitating action in the psychoaffective elaboration and maturation. The author
      stresses the importance of agonistic molecules in the serotonin which seem to
      favour a psychological "working-through" probably because of the lifting of
      compulsive-obsessive mechanisms present in chronic an residual depressions. The
      authors underlines the importance of naturalistic and pragmatical studies as an
      alternative or as a complement to protocolar and controlled studies which are
      often biased. These biases are increased because of complicated psychometrics and
      by recent legal measures which tend to lessen the clinical credibility of these
      "controlled" studies.

PMID- 1343553
TI  - [The ego and dysphonias].
AB  - Every psycho-affective disorder may be a factor of language constitution and
      communication disorders. The study of it, particularly in psychosis is a major
      sign for diagnosis. Linguistic troubles are correlate with mind perturbations and
      the psychotic language is symptomatic. The most suggestive example is
      schizophrenia. Rythm and sound stay, yet semantics and syntactics expressions are
      down.

PMID- 1343554
TI  - [What is meant by clinical research in psychiatry?].
AB  - The untiring questioning on the part of the two sources, somatic and
      psychological, in illness make a pair with contradistinction between "clinical"
      research and "scientific" research. However, they are good theoretic and
      pragmatic arguments in favour of their complementarity and full respective
      lawfullness. In this purpose, one had to scrutinize the explicit and implicit
      definitions, too often adulterated by presuppositions and exclusive preferences.

PMID- 1343555
TI  - [Automatic actions with amnesia induced by taking hypnotic drugs. Association
      with personal and familial history of somnambulism and epilepsy].
AB  - A family which combined sleep-walking drug-induced sleep-walking and epilepsy is
      reported. This co-morbidity suggest various mechanisms which could explain drug
      induced sleep-walking. We stated the hypothesis that these behaviors were
      epileptic states due to a mini-withdrawal syndrome. This mini-withdrawal
      including of course a rebound of anxiety and insomnia during the day, but also a
      pro-convulsivant effect.

PMID- 1343556
TI  - [Burn-out syndrome: reality of mode of expression?].

PMID- 1343557
TI  - The biology of cyclic nucleotide phosphodiesterases.

PMID- 1343558
TI  - Conversion of human low density lipoprotein into a very low density lipoprotein
      like particle in vitro.
AB  - The lipid substrate specificity of Manduca sexta lipid transfer particle (LTP)
      was examined in in vitro lipid transfer assays employing high density lipophorin
      and human low density lipoprotein (LDL) as donor/acceptor substrates.
      Unesterified cholesterol was found to exchange spontaneously between these
      substrate lipoproteins, and the extent of transfer/exchange was not affected by
      LTP. By contrast, transfer of labeled phosphatidylcholine and cholesteryl ester
      was dependent on LTP in a concentration-dependent manner. Facilitated
      phosphatidylcholine transfer occurred at a faster rate than facilitated
      cholesteryl ester transfer; this observation suggests that either LTP may have an
      inherent preference for polar lipids or the accessibility of specific lipids in
      the donor substrate particle influences their rate of transfer. The capacity of
      LDL to accept exogenous lipid from lipophorin was investigated by increasing the
      high density lipophorin:LDL ratio in transfer assays. At a 3:1 (protein) ratio in
      the presence of LTP, LDL became turbid (and aggregated LDL were observed by
      electron microscopy) indicating LDL has a finite capacity to accept exogenous
      lipid while maintaining an overall stable structure. When either isolated human
      non B very low density lipoprotein (VLDL) apoproteins or insect apolipophorin III
      (apoLp-III) were included in transfer experiments, the sample did not become
      turbid although lipid transfer proceeded to the same extent as in the absence of
      added apolipoprotein. The reduction in sample turbidity caused by exogenous
      apolipoprotein occurred in a concentration-dependent manner, suggesting that
      these proteins associate with the surface of LDL and stabilize the increment of
      lipid/water interface created by LTP-mediated net lipid transfer. The association
      of apolipoprotein with the surface of modified LDL was confirmed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis analysis, and scanning
      densitometry revealed that apoLp-III bound to the surface of LDL in a 1:14
      apoB:apoLp-III molar ratio. Electron microscopy showed that apoLp-III-stabilized
      modified LDL particles have a larger diameter (29.2 +/- 2.6 nm) than that of
      control LDL (22.7 +/- 1.9 nm), consistent with the observed changes in particle
      density, lipid, and apolipoprotein content. Thus LTP-catalyzed vectorial lipid
      transfer can be used to introduce significant modifications into isolated LDL
      particles and provides a novel mechanism whereby VLDL-LDL interrelationships can
      be studied.

PMID- 1343559
TI  - Isozymes of cyclic-3',5'-nucleotide phosphodiesterases in renal epithelial LLC
      PK1 cells.
AB  - Metabolism of cAMP and cGMP by the major types (families) of cyclic-3',5'
      nucleotide phosphodiesterases (PDE) was studied in confluent renal epithelial LLC
      PK1 cells grown in vitro. LLC-PK1 cells mainly contain the cAMP-specific rolipram
      sensitive PDE type-IV (PDE-IV), the Ca(2+)-calmodulin dependent PDE type-I and
      cGMP-specific PDE type-V; all these PDEs are mainly localized in cytosol.
      Analysis of PDE activities in soluble extract of LLC-PK1 cell homogenate by FPLC
      ionex chromatography on Mono-Q column also disclosed the presence of low
      activities of cGMP-stimulated PDE-II and PDE-III. Moreover, activity of PDE-IV
      was resolved into four distinct chromatographic peaks. The increase of cAMP level
      in response to incubation of intact LLC-PK1 cells with vasopressin (AVP) was
      markedly enhanced in the presence of rolipram, but not in the presence of other
      PDE isozyme-specific inhibitors. Incubation with AVP and atriopeptin (ANP)
      together resulted in increase in cGMP and a small decrease of cAMP accumulation
      in LLC-PK1 cells. Results of these studies first show that the LLC-PK1 cells
      contain all five major types of PDE isozymes where PDE-IV, PDE-I and PDE-V are
      quantitatively predominant. The rolipram-sensitive PDE-IV, present in several
      chromatographically distinct forms, appears to be the key PDE isozyme involved in
      control of cAMP generated in response to stimulation by AVP in LLC-PK1 cells.

PMID- 1343560
TI  - Congenital rubella syndrome among the Amish--Pennsylvania, 1991-1992.
AB  - From February through May 1991, an outbreak of rubella occurred among the Amish
      in Pennsylvania that was part of a widespread rubella outbreak reported among the
      Amish in at least six states during 1991 (1). The Pennsylvania Department of
      Health (PDH), in cooperation with CDC, conducted an investigation to document
      cases of rubella among pregnant Amish women in Lancaster County and a cohort
      study to estimate the risk for congenital rubella syndrome (CRS) among infants
      born to Amish mothers from November 1, 1991, through January 31, 1992. This
      report summarizes investigation and study findings.

PMID- 1343561
TI  - Anaphylactic reaction during immunotherapy related to alcohol consumption.
AB  - A case of anaphylaxis related to alcohol consumption during immunotherapy is
      reported. We advise to consider whether there has been noticeable alcohol
      consumption prior to each injection.

PMID- 1343562
TI  - 99mTechnetium-dimercaptosuccinic acid scan in the diagnosis of acute
      pyelonephritis in children: relation to clinical and radiological findings.
AB  - Seventy-two children, 59 girls and 13 boys, 0.1-15.9 (median 1.1) years of age,
      with acute pyelonephritis (APN) were investigated with the aid of a
      dimercaptosuccinic acid (DMSA) scan, renal ultrasonography (US) and a
      desmopressin test within 5 days of admission. Sixty-two children were
      reinvestigated approximately 2 months later when intravenous urography (IVU) and
      micturition cysto-urethrography were also performed. During infection, 92% of the
      children showed changes in the DMSA scan with 69% by US, and the two
      investigations agreed in 58% of the kidneys. At follow-up, 68% showed changes in
      the DMSA scan, 47% by US and 48% by IVU. The DMSA scan and IVU agreed in 60% of
      the kidneys. Twenty-nine percent of the children had vesico-ureteric reflux
      (VUR). The presence of grade greater than or equal to 3 VUR was associated with
      greater defects on the DMSA scan during infection, and at follow-up with a higher
      frequency of persistent changes compared with no VUR (P less than 0.02 and 0.01,
      respectively). During infection the size of the defect on the DMSA scan
      correlated with renal volume and C-reactive protein and inversely with the
      glomerular filtration rate, and at follow-up it correlated inversely with the
      renal concentration capacity. The DMSA scan is a sensitive method for diagnosing
      and localizing APN in children, and findings on DMSA scan show a weak but
      significant correlation with routine clinical and radiological parameters. It is
      suggested that persistent renal damage after APN in children without VUR may be
      more common than previously assumed.

PMID- 1343563
TI  - Plasma ionized calcium and blood lactate concentrations are inversely associated
      in human lactic acidosis.
AB  - Plasma ionized calcium [Ca++] concentrations are decreased in patients having
      lactic acidosis. To further investigate this observation, we prospectively
      studied nine critically ill patients who had lactic acidosis and measured
      arterial pH, PCO2, [Ca++], lactate, and albumin concentrations. We found a strong
      association between decreased [Ca++] and increased plasma lactate concentrations
      (r2 = 0.78, p less than or equal to 0.001). This unexpected association--[Ca++]
      usually increases with increasing acidosis--might be clinically important and the
      mechanism deserves further investigation.

PMID- 1343564
TI  - [Pathogenesis of peptic ulcer: role of Helicobacter pylori gastritis and its
      course during antibiotic and/or antisecretory treatment].
AB  - A systematic investigation of the histologic pattern of antral and corpus
      gastritis has been carried out in 1177 patients with various clinical conditions.
      An increased rate and severity of antral mucosa gastritis activity as well as
      surface epithelium cytotoxic lesions and Helicobacter pylori colonization,
      coupled with low rates and severity of the same parameters in corpus mucosa
      gastritis (usually of superficial nature so as to spare the integrity of
      acidopeptic glands) were the main features associated with active gastroduodenal
      peptic ulcer or antroduodenal mucosal erosions. Simultaneous antisecretory
      (omeprazole) and antibiotic treatment of duodenal ulcer patients led to the
      eradication of Helicobacter in 54 to 82% of patients when amoxycillin alone was
      used as antibiotic, and up to 94% of patients, when metronidazole was added to
      amoxycillin, as against none of patients treated with omeprazole alone, despite
      effective healing of their ulcer lesion. Very low (usually less than 5% per year)
      recurrency rates are reported in the literature for patients undergoing bacterial
      eradication, as against 50 to 80% in non-eradicated patients whose ulcer was
      healed by short term antisecretory drug treatment.

PMID- 1343565
TI  - Suprapubic catheterisation and bowel injury.

PMID- 1343566
TI  - Anemia in the adolescent athlete.
AB  - Anemia is a common disorder among adolescents regardless of level of physical
      activity. The major cause of anemia in adolescents is nutritional iron
      deficiency. Iron metabolism may be altered in some athletes training and
      competing in endurance sports. The dilutional "sports anemia" that can occur in
      the more elite adolescent athlete may be an adaptation to aerobic conditioning.
      Screening for anemia in adolescent athletes is warranted because anemia may
      contribute to morbidity and diminished exercise performance. Current concepts and
      controversies regarding anemia in adolescent athletes are addressed, and
      application of this information to preparticipation physical examinations is
      examined.

PMID- 1343567
TI  - Should we try to supplement the growth retarded fetus? A cautionary tale.

PMID- 1343568
TI  - The effects of calcium site occupancy and reagent length on reactivity of
      calmodulin lysyl residues with heterobifunctional aryl azides. Mapping
      interaction domains with specific calmodulin photoprobe derivatives.
AB  - The relationship of structural and functional moieties on calmodulin is important
      in all venues of cell activity. In this study, we investigate the effect of
      lysine modification on calmodulin function. Azidosalicylate reagents containing
      different "linker arm" lengths, between the photoactive terminus and an amine
      reactive N-hydroxysuccinimidyl ester moiety were used to modify calmodulin
      lysines at three different positions in a calcium-dependent manner. The short
      cross-linker, (ASNE-2 (where ASNE represents azidosalicylate N
      hydroxysuccinimidyl ester), modifies Lys-75, whereas the longer reagent, ASNE-6,
      modifies lysines 21, 75, and 94. The modification of these different lysines is
      shown to be calcium-dependent. At 1-100 microM levels of calcium, only Lys-94 is
      modified, suggesting that modification of this residue is directed by both the
      binding of calcium to calcium-binding loops III and IV and the hydrophobic pocket
      exposed between these two loops as a result of calcium binding. At higher calcium
      concentrations (> 200 microM), where sites I and II become filled, modification
      of Lys-21 or Lys-75 also was observed. All the modified calmodulins were able to
      stimulate 3',5'-cyclic-nucleotide phosphodiesterase fully although the Kact for
      the Lys-75 and Lys-21 derivatives increased 10- and 50-fold, respectively. None
      of the modifications affected the activation of erythrocyte plasma membrane
      Ca(2+)-ATPase. Only the ASNE-6 Lys-75 derivative showed efficient (40%)
      photocross-linking to the Ca(2+)-ATPase. The ASNE-2 Lys-75 derivative as well as
      the ASNE-6 Lys-21 and Lys-94 derivatives did not show efficient calcium-dependent
      photocross-linking to this enzyme.

PMID- 1343569
TI  - Malignant seeding of the needle track during stereotaxic core needle breast
      biopsy.
AB  - Early reports demonstrated the diagnostic advantage of large-core (14-gauge)
      biopsy over fine-needle aspiration biopsy of nonpalpable lesions of the breast
      without apparent significant increase in morbidity. A case of malignant seeding
      of the needle track after a large-core biopsy of a mucinous carcinoma of the
      breast is documented. The potential for increased risk of tract seeding of
      malignancy must be considered.

PMID- 1343570
TI  - Outcome of carotid artery resection for neoplastic disease: a meta-analysis.
AB  - PURPOSE: To determine the neurologic morbidity and oncologic effectiveness of
      carotid resection in patients with advanced squamous cell carcinoma of the head
      and neck. METHODS: A retrospective review of all published cases of squamous cell
      carcinoma of the head and neck treated by carotid resection was performed.
      RESULTS: A major neurologic complication occurred in 17% of patients. Neurologic
      morbidity was not associated with the method of carotid artery reconstruction.
      Two-year disease-free survival was 22%. The majority of recurrences were local or
      regional. Comparison of survival of this group to a similarly staged control
      group demonstrated no significant difference in survival. CONCLUSION: This review
      of the literature suggests that elective carotid resection achieves significant
      local/regional control of disease and that carotid artery involvement is not a
      poor prognostic factor in patients with advanced head and neck cancer.

PMID- 1343571
TI  - An appraisal of temperature assessment by infrared emission detection tympanic
      thermometry.

PMID- 1343572
TI  - Mohs micrographic surgery and the practitioner.

PMID- 1343573
TI  - Imaging of the knee.
AB  - Acute and chronic knee dysfunction is a common clinical problem faced by
      physicians treating patients with musculoskeletal disorders. While standard
      roentgenograms provide most of the information needed to assess these disorders,
      the role of magnetic resonance imaging (MRI) is rapidly increasing in the
      diagnostic evaluation of soft-tissue, ligament, tendon, and osseous
      abnormalities. This article focuses on the role of MRI in the evaluation of
      disorders of the knee.

PMID- 1343574
TI  - Views on AuD.

PMID- 1343575
TI  - Clinical quiz. The nephrotic syndrome was secondary to renal amyloidosis.

PMID- 1343576
TI  - AIDS/HIV prevention--the American experience.

PMID- 1343577
TI  - Accessory nipples: any relationship to urinary tract malformation?
AB  - One hundred two infants and children age 3 days to 16.5 years, found to have
      accessory nipples (AN), were enrolled in this study. They were categorized by
      ethnic origin, sex, positive family history of AN, and number, site, and shape of
      AN, to determine factors for increased risk of anomalies of the urinary tract.
      Physical and ultrasound examinations of the abdomen did not reveal evidence of
      urinary tract malformation in any of the children. The results of this survey
      support the contentions that AN are not associated with urinary tract
      malformations, and that no further investigation is required in children with
      solitary AN.

PMID- 1343578
TI  - [National study of lipids in coronary patients].
AB  - Although coronary atherosclerosis is considered to have several etiologic factors
      there is little doubt that elevated plasmatic cholesterol level is the main one.
      The present study was carried out because of the lack of information concerning
      cholesterol, lipoproteins and triglycerides levels in the coronary population in
      Argentina. Patients were selected on the basis of a demonstrated coronary
      atherosclerosis, detected either by an abnormal coronary arteriogram or a
      documented myocardial infarction. Total seric cholesterol (TC), low density
      lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and
      triglycerides (TG) were determined in a core laboratory. Blood samples were
      obtained after a 12 hour fasting period. LDL-C was also calculated by the
      Friedewald formula. Patients were stratified according to sex, age, having or not
      myocardial infarction, type (Q or non Q wave) and localization of myocardial
      infarction. A total of 653 patients were included. The mean values obtained were:
      TC 227 +/- 1.8 mg/dL; LDL-C 153 +/- 1.8 mg/dL; HDL-C 48 +/- 0.4 mg/dL and TG 180
      +/- 3.6 mg/dL (expressed as mean +/- SE). Mean values in the male and female
      subsets are given in Table 1. In women, TC, LDL-C and HDL-C are significantly
      higher than in men. Cholesterol values according to age are displayed in Table 3.
      Young people have higher TC and LDL-C mean values than older ones. Different
      cholesterol levels were not observed when the coronary population in our study
      was stratified according to the presence or not of previous myocardial infarction
      (Table 4).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343579
TI  - Development of a teaching model for coronal access to the canine dentition.
AB  - A dolichocephalic canine skull was utilized to develop a teaching and study model
      for coronal access cavity preparation of the dentition. The teeth from the right
      side of the skull were extracted. Each tooth was radiographed in two planes to
      localize the "ideal" endodontic access point. Barium markers were placed over
      these points and each tooth was radiographed again to confirm the appropriate
      location of the marker. Access was created by drilling through the barium marker.
      Then, K-files were inserted through the access preparation into the root canal
      system. The teeth were radiographed with the K-files in place to verify straight
      pathways to the apices. Straight line access to the apex was obtained in all
      teeth. Creation of this model provides an opportunity for the veterinary dental
      student to develop and refine skills used in performing endodontic therapy. The
      model can be utilized by the veterinary dental practitioner in clinical practice.

PMID- 1343580
TI  - Veterinary dental demonstration models.
AB  - This article is about dental models and their construction. It is meant to be
      informative, entertaining and, hopefully, a little lighthearted. The use of
      dental models in the veterinary practice has become commonplace. The models are
      useful for demonstrating to clients and colleagues various dental pathologies and
      procedures.

PMID- 1343581
TI  - Intracanal calcium hydroxide therapy--the Webber technique.
AB  - Calcium hydroxide powder has been used as a treatment medication for different
      pathologies of the teeth. This article describes the physiological effects and
      general principles involved in using calcium hydroxide. The indications for its
      use and the contraindications are described. Filling and refilling the root canal
      with calcium hydroxide using the Webber technique induces a calcified tissue
      barrier and stimulates osteogenic healing. A case report using the Webber
      technique is included.

PMID- 1343582
TI  - Replantation of a maxillary canine tooth after traumatic avulsion in a dog.
AB  - An infrequent traumatic injury in dogs is avulsion of a tooth from its alveolus.
      The management of the avulsed tooth is complex. This report describes the
      treatment of a traumatically avulsed maxillary canine tooth in a dog.
      Replantation and splinting of the tooth was performed. Despite a protracted
      extraoral time, follow up clinical and radiographic assessment of the tooth
      indicated successful replantation.

PMID- 1343583
TI  - The role of taurine and its derivatives on cellular hypoxia: a physiological
      view.
AB  - Taurine (2-aminoethanosulfonic acid) appears to have an important role in cell
      protection against hypoxia. The mechanistic basis by which this amino acid and
      its derivatives are involved on these events, in brain or in other tissues, are
      discussed considering the antioxidant role of hypotaurine and some of its
      derivatives.

PMID- 1343584
TI  - The inhibitory action of chlorogenic acid on the intestinal iron absorption in
      rats.
AB  - The polyphenols are part of the composition of many foods, it is known the
      inhibitory effect of tea and coffee through the tannins on iron intestinal
      absorption; the "yerba mate" (Ilex Paraguarensis) is a beverage widely used in
      South America, that has a high content of a polyphenol named chlorogenic acid.
      The present work shows the effect of this substance in nonhem iron absorption. An
      intestinal loop, was made in rats, to form a closed cavity in a small section of
      intestine tieing it from the pilorous to a distance of six cm. In this closed
      cavity a solution of 59Fe was injected with different doses of chlorogenic acid;
      it was living 20, 40 and 120 minutes into the loop, and after this different
      times, the blood, spleen, liver, femur and intestine were removed to measure the
      59Fe uptake to be compared with the control group. The results gave an intense
      inhibitory effect on the intestinal iron absorption with doses of 0.58 and 1.7 mM
      per rat of chlorogenic acid at the different times studied.

PMID- 1343585
TI  - Caffeine effects on heart muscle energetics: species differences.
AB  - The effects of caffeine (1mM) on energy expenditure and mechanical parameters in
      rat and toad perfused heart ventricles were examined at various stimulation
      frequencies. While in rat muscles caffeine significantly depressed developed
      tension and maximal rates of contraction and relaxation at all frequencies
      tested, in toad ventricle a slight positive inotropic effect was observed. Even
      though caffeine did not alter total contraction time in both preparations, in the
      rat ventricle the last part of relaxation was prolonged. In rat ventricle in the
      presence of caffeine, the ratios between active heat production per beat and
      either developed tension or tension time integral increased at all frequencies
      tested (+303 +/- 47 microJ.mN-1 x g-1 and +1.21 +/- 0.13 mJ.mN-1 x s-1 x g-1
      respectively) indicating a decrease in contractile economy. In toad ventricle no
      changes on these ratios were observed. The fact that only in rat ventricle
      caffeine decreased muscle economy suggests that caffeine affects a system that is
      active in rat ventricle but it is not operative in toad ventricle. This gives
      support to the hypothesis that if in rat ventricle SR-Ca pump (1 ATP hydrolyzed/2
      Ca transported) is inhibited by caffeine cytosolic Ca would have to be removed by
      alternative mechanisms such as Na-Ca exchanger or sarcolemmal Ca pump both with a
      higher rate of ATP hydrolysis (1 ATP hydrolyzed/Ca transported) with the
      consequent decrease in muscle economy. Resting heat production was increased by
      caffeine in both preparations and the magnitude of the increment (+3.0 +/- 0.6
      mW.g-1 and +0.75 +/- 0.21 mW.g-1 for rat and toad ventricle respectively) also
      correlates with the different degree of SR activity in both species.

PMID- 1343586
TI  - Norepinephrine--stimulated activity of hypothalamic adenylate cyclase varies
      throughout the estrous cycle of the female rat.
AB  - The activity of hypothalamic adenylate cyclase was studied throughout the estrous
      cycle of the female rat. The activity of the enzyme was determined in particulate
      fractions obtained from hypothalami of rats killed at 10.00 h and 16.00 h of the
      4-day estrous cycle. The activity was assayed in the presence of norepinephrine
      (10(-8) to 10(-3) M) by the capacity to produce adenosine 3',5' cyclic
      monophosphate. The basal activity of adenylate cyclase was higher in the morning
      of estrus than at any other time during the cycle. Norepinephrine-stimulated
      adenylate cyclase activity, as assessed by the apparent affinity (Kd) and
      apparent maximum effect, varied during the cycle, showing highest affinity,
      lowest Kd, in the afternoon of proestrus. The highest level of apparent maximum
      effect was also found in the afternoon of proestrus declining on diestrous day 2,
      diestrous day 1 and estrus. The norepinephrine stimulated activity was
      significantly inhibited by phenoxybenzamine, an alpha-blocker, in the morning of
      diestrus day 1, whereas on the day of diestrus day 2 and proestrus it was
      inhibited by the beta-adrenoblocker, propranolol. A similar degree of inhibition
      by alpha- and beta-blockers was observed in the morning of estrus. These results
      indicate that the hypothalamic adenylate cyclase coupled to adrenergic receptors
      shows dynamic changes throughout the estrous cycle.

PMID- 1343587
TI  - Fluoride and phosphatidylserine induced inhibition of cytosolic insulin-degrading
      activity.
AB  - Cytosol (C) (100,000 x g/60 min, supernatant) from liver, brain and testis
      (Wistar male rats) are shown to contain insulin degrading activity (C-IDA). The
      regulation of C-IDA in these fractions by ligands that activate G protein and PKC
      were examined C-IDA from liver, brain and testis was inhibited 76%; 64% and 50%
      by 50 mM F- respectively. Chromatography of C fraction from liver on Sephadex G
      50 in presence of 1 M (NH4)2SO4 and 20% (v/v) glycerol (experimental condition to
      remove guanine nucleotides from G proteins) decreased in about 3-fold aluminum
      fluoride effect on C-IDA. Mg++ (from 5mM to 10 mM) enhanced fluoride effects by
      inhibiting fully C-IDA. Phosphatidylserine in presence of ATP completely
      inhibited C-IDA; this inhibition was 31.3% mediated by a phosphorylation
      reaction. It is concluded that cytosol from different tissues contain proteins
      capable to associate ligands as aluminum fluoride and PS to regulate C-IDA. It is
      proposed a mechanism of protein-protein interaction to modulate C-IDA.

PMID- 1343588
TI  - Regulation of potassium conductance in the cellular membrane at early
      embryogenesis.
AB  - At the early stages of development of the fresh water fish loach (Misgurnus
      fossilis) the resting membrane potential (Er) of cleaving cells oscillates
      periodically with an amplitude of 8-12 mV. Er oscillation correlates with the
      cell cycle and is accompanied by changes of K+ conductivity. Two types of K(+)
      selective ionic channels with conductance of approximately 70 and 25 pS in
      symmetrical (150 mM KCl) solution were observed in the membrane of cleaving loach
      embryos. 'High' conductance and 'low' conductance channels were recorded in
      approximately 90% and 10% of patches investigated (n = 275), respectively? The
      activity of 'high' conductance channels was regulated by the application of
      pressure to the membrane, ie these channels were stretch-activated (SA). The
      activity of SA channels changes dramatically during the cell-cleavage cycle. At
      the beginning of interphase the probability of SA channels being in the open
      state (P0) was minimal, while at prometaphase the probability was increased 10
      100-fold. Application of ATP to the cytoplasmic inside-out patches induced a
      reversible elevation of stretch sensitivity of the SA channels in 50% of the
      patches, while the non-hydrolyzable analogue of ATP was not effective. Combined
      application of ATP, cAMP and cAMP-dependent protein kinase (PK) induced a
      reversible elevation in the SA channel activity while inhibitors of PK prevented
      its activating effects. Phosphatase inhibitors prolonged the activating effect of
      PK on SA channels. We propose that oscillations of the resting potential during
      the cell-cleavage cycle arise due to modulation of SA channel sensitivity to
      stretch through cAMP-dependent phosphorylation.

PMID- 1343589
TI  - Charge movement and Ca2+ release in normal and dysgenic foetal myotubes.
AB  - Intramembrane charge movement and Ca2+ release from sarcoplasmic reticulum was
      studied in foetal skeletal muscle cells from normal and mutant mice with
      'muscular dysgenesis' (mdg/mdg). It was shown that: 1) unlike normal myotubes, in
      dysgenic myotubes membrane depolarization did not evoke calcium release from the
      sarcoplasmic reticulum; 2) when all ionic currents are pharmacologically
      suppressed, membrane depolarization produced an asymmetric intramembrane charge
      movement in both normal and dysgenic myotubes. The relationship between the
      membrane potential and the amount of charge movement in these muscles could be
      expressed by a two-state Boltzmann equation; 3) the maximum amount of charge
      movement associated with depolarization (Qon max) in normal and in dysgenic
      myotubes was 6.3 +/- 1.4 nC/microF (n = 6) and 1.7 +/- 0.3 nC/microF (n = 6)
      respectively; 4) nifedipine (1-20 microM) applied to the bath reduced Qon max by
      about 40% in normal muscle cells. In contrast, the drug had no significant effect
      on the charge movement of dysgenic myotubes; and 5) the amount of nifedipine
      resistant charge movement in normal and in dysgenic myotubes was 3.5 nC/microF (n
      = 3) and 1.7 nC/microF 1 maximum (n = 3), respectively.

PMID- 1343590
TI  - Spiral waves and intracellular calcium signalling.
AB  - Confocal imaging of intracellular Ca2+ brings a new level of resolution to the
      study of hormonal control of intracellular Ca2+ release. This approach has
      demonstrated the existence of pulsatile circular and spiral waves of Ca+ release
      induced by receptor activation. The data obtained by confocal imaging support a
      new framework for understanding intracellular Ca2+ signalling. The goal of this
      chapter is to review our data on the complexity of intracellular Ca2+ release in
      Xenopus oocytes, introduce the concept of Ca2+ excitability as a model for Ca2+
      release and discuss the implications for encoding intracellular signal
      information.

PMID- 1343591
TI  - The role of calcium in prolonged modification of a GABAergic synapse.
AB  - Caudal hair cell impulses cause postsynaptic inhibition of ipsilateral type B
      photoreceptors in the snail Hermissenda. This inhibition is shown to be GABAergic
      according to a number of criteria. HPLC, mass spectrophotometric, and
      immunocytochemical techniques demonstrated the presence of GABA in the hair cells
      and their axons. GABA agonists and antagonists mimic and block the synaptic
      effect in a manner consistent with endogenous GABAergic transmission. Other
      properties, including I-V relations, conductance changes and reversal potentials,
      are comparable for exogenous GABA responses and endogenous effects of the hair
      cell impulses. This inhibitory synapse has been found to undergo a long-lasting
      transformation into an excitatory synapse if GABA release is paired with post
      synaptic depolarization. GABA, via GABAA and GABAB receptors in the B cell,
      causes the opening of calcium sensitive chloride and potassium channels that
      leads to the post-synaptic hyperpolarization. GABA also induces a long-lasting
      intracellular calcium elevation at the terminal branches of the B cell that
      greatly outlasts the voltage responses. Synaptic transformation induced by
      pairings is caused by a decrease in both GABA induced chloride and potassium
      conductances in the post-synaptic B cell, as well as a significant prolongation
      of the intracellular calcium accumulation in the B cell's terminal axonal
      branches.

PMID- 1343592
TI  - The role of cytoplasmic calcium in photoreceptor light adaptation.
AB  - The process of light adaptation in vertebrate rod and cone photoreceptors is
      believed to involve a diffusible cytoplasmic messenger. Two lines of evidence
      indicate that photoreceptor light adaptation is mediated by a light-induced fall
      in cytoplasmic calcium concentration (Ca2+i). First, if changes in calcium
      concentration are slowed by the incorporation of calcium chelators into the
      photoreceptor cytoplasm then light adaptation is slowed also. Second, if the
      normal control of Ca2+i is prevented by simultaneously minimising calcium influx
      and efflux across the outer segment membrane by means of external solution
      changes, then all of the manifestations of light adaptation are abolished.
      Furthermore, recent results show that changes in Ca2+i imposed in the absence of
      light are sufficient to cause at least some of the manifestations of light
      adaptation. Together these results indicate that calcium acts as the messenger of
      light adaptation in the photoreceptors of both lower and higher vertebrates.

PMID- 1343593
TI  - Intracellular Ca2+ stores in neurons. Identification and functional aspects.
AB  - Various aspects of the rapidly exchanging intracellular Ca2+ stores of neurons
      and nerve cells are reviewed: their multiplicity, with separate sensitivity to
      either the second messenger, inositol 1,4,5-trisphosphate, or ryanodine-caffeine
      (the latter stores are probably activated via Ca(2+)-induced Ca2+ release); their
      control of the plasma membrane Ca2+ permeability, via the activation of a
      peculiar type of cation channels; their ability to sustain localized
      heterogeneities of the [Ca2+]i that could be of physiological key-importance.
      Finally, the molecular composition of these stores is discussed. They are shown
      (by high resolution immunocytochemistry and subcellular fractionation) to
      express: i) a Ca2+ ATPase responsible for the accumulation of the cation; ii)
      Ca2+ binding protein(s) of low affinity and high capacity to keep Ca2+ stored;
      and iii) a Ca2+ channel, activated by either one of the mechanisms mentioned
      above, to release Ca2+ to the cytosol. Results obtained in Purkinje neurons
      document the heterogeneity of the stores and the strategical distribution of the
      corresponding organelles (calciosomes; specialized portions of the ER) within the
      cell body, dendrites and dendritic spines.

PMID- 1343594
TI  - Presynaptic receptors for FMRFamide, histamine and buccalin regulate
      acetylcholine release at a neuro-neuronal synapse of Aplysia by modulating N-type
      Ca2+ channels.
AB  - At an identified neuro-neuronal synapse of the buccal ganglion of Aplysia,
      quantal release of acetylcholine (ACh) is increased by FMRFamide and decreased by
      histamine or buccalin. Activation of presynaptic receptors for these
      neuromodulators modifies a presynaptic Ca2+ current which is nifedipine-resistant
      and omega-conotoxin-sensitive. The voltage-sensitivity of these N-type Ca2+
      channels is increased by FMRFamide and decreased by histamine through the
      intermediate of G proteins. Buccalin does not implicate G proteins and reduces
      the Ca2+ current without affecting the voltage-sensitivity of N-type Ca2+
      channels. The possibility of relating the shifts in voltage-dependence of the
      Ca2+ current induced by FMRFamide and histamine to the phosphorylation state of
      the N-type Ca2+ channels is discussed. A scheme for the complex regulation of ACh
      release by presynaptic auto- and heteroreceptors is proposed.

PMID- 1343595
TI  - Divalent cation changes in cerebellar Purkinje cells after climbing fiber
      deafferentation.
AB  - A secondary ion mass spectrometry (SIMS) microscope was used to detect
      intracellular stores of calcium, magnesium, sodium and potassium. Measurements
      were made in semithin sections of fixed tissues of normal and climbing fiber
      deafferented cerebellar cortex. Quantitative data were collected from 150 microns
      diameter image fields in the molecular and granule layers. The results indicate
      smaller quantities of both calcium and magnesium in the deafferented cerebellar
      cortex compared to the normals, the molecular as well as the granule layer being
      affected. The results are discussed in terms of the usefulness and limitations of
      the SIMS microscope for histological preparations.

PMID- 1343596
TI  - The metabotropic glutamate receptor (MGR): pharmacology and subcellular location.
AB  - A pharmacological characterization of the metabotropic glutamate receptor (MGR)
      was performed in striatal neurons. Among the excitatory amino acid receptor
      antagonists tested, only D, L-2-amino-3-phosphonopropionate (D, L-AP3) inhibited
      QA-induced inositol phosphate (InsP) formation in a competitive manner (mean pKi
      = 4.45 +/- 0.43, n = 4). However, this drug was a partial agonist of MGR since it
      stimulated the inositol-phosphate formation. We found that D, L-AP3 also
      inhibited NMDA-induced calcium increase, in a competitive manner (mean pIC50 =
      4.34 +/- 0.22, n = 8, and mean pKi = 3.7 +/- 0.11 n = 5). 1 mM of the ionotropic
      agonists alpha-amino-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate
      (KA) or domoate (DO) (100 microM or higher) induced a significant InsP formation
      in striatal neurons. The InsP responses induced by all these agonists were
      totally blocked by the phorbol ester phorbol-12,13-dibutyrate (PdBu), but not by
      atropine or prazosin. Agonist-induced increases of intracellular calcium
      concentrations ([Ca2+]i) were insensitive to PdBu, suggesting that all these
      substances were able to stimulate the MGR in striatal neurons. Trans-1-amino
      cyclopentyl-1,3-dicarboxylate (trans-ACPD) evoked dose-dependent inositol
      phosphate formations with an EC50 of 29 microM but had no significant effect on
      NMDA or AMPA receptors, as measured by the patch clamp technique. In the presence
      of 30 microM of AMPA, trans-ACPD induced a significant release of arachidonic
      acid (AA) in striatal neurons. No important AA release was observed by any of
      these agonists alone. 56 mM K+ did not mimic AMPA in this associative
      ionotropic/metabotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343597
TI  - Ca2+ signalling in postsynaptic dendrites and spines of mammalian neurons in
      brain slice.
AB  - Postsynaptic Ca2+ changes are involved in control of cellular excitability and
      induction of synaptic long-term changes. We monitored Ca2+ changes in dendrites
      and spines during synaptic and direct stimulation using high resolution
      microfluorometry of fura-2 injected into CA3 pyramidal neurons in guinea pig
      hippocampal slice. When driven by current injection from an intracellular
      electrode or with synaptic stimulation, postsynaptic Ca2+ accumulations were
      highest in the proximal dendrites with a pronounced fall-off towards the soma and
      some fall-off towards more distal dendrites. Muscarinic activation by low
      concentrations of carbachol strongly increased intradendritic Ca2+ accumulation
      during directly-evoked repetitive firing. This enhancement occurred in large part
      because muscarinic activation suppressed the normal Ca(2+)-dependent activation
      of K-channels that mediates adaptation of firing. Repetitive firing of
      cholinergic fibers in the slice reproduced the effects of carbachol. Inhibition
      of acetylcholine-esterase activity by eserine enhanced the effects of repetitive
      stimulation of chlolinergic fibers. All effects were reversible and were blocked
      by the muscarinic antagonist atropine. Ca2+ accumulations in postsynaptic spines
      might be the basis of specificity of synaptic plasticity. With selective
      stimulation of few associative/comissural fibers, Ca2+ accumulated in single
      postsynaptic spines but not in the parent dendrite. With strong stimulation,
      dendrite levels also increased but spine levels were considerably higher. The
      NMDA-receptor antagonist AP-5 blocked Ca(2+)-peaks in spines, but left Ca2+
      changes in dendrite shafts largely unaffected. Sustained steep Ca2+ gradients
      between single spines and the parent dendrite, often lasting several minutes,
      developed with repeated stimulation. Our results demonstrate a spine entity that
      can act independent from the dendrite with respect to Ca(2+)-dependent processes.
      Muscarinic augmentation of dendritic Ca2+ levels might reduce diffusional loss of
      Ca2+ from hot spines into the parent dendrite, thus supporting cooperativity and
      associativity of synaptic plasticity.

PMID- 1343598
TI  - Carbachol-stimulated calcium entry in SH-SY5Y human neuroblastoma cells: which
      route?
AB  - M3 muscarinic receptors expressed on SH-SY5Y human neuroblastoma cells are linked
      to phosphoinositide turnover and rises in [Ca2+]i. The rise in [Ca2+]i is
      biphasic with the peak phase being due to release from an intracellular
      Ins(1,4,5)P3-sensitive site and the plateau phase being due to Ca2+ entry across
      the plasma membrane. Ca2+ entry does not appear to involve voltage sensitive Ca2+
      channels, a pertussis toxin sensitive G-protein-operated Ca2+ channel or
      Ins(1,4,5)P3/Ins(1,3,4,5)P4-operated Ca2+ channel. We suggest that carbachol
      stimulated Ca2+ entry in SH-SY5Y human neuroblastoma cells occurs via receptor
      operated Ca2+ channels and through capacitive refilling.

PMID- 1343599
TI  - Calmodulin and cell cycle control.
AB  - Previous studies have indicated a role for the calcium receptor calmodulin in the
      control of eukaryotic cell proliferation. Using a molecular genetic approach in
      the filamentous fungus Aspergillus nidulans we have shown that CaM is required
      for cell cycle progression at multiple points in the cell cycle. Construction of
      an A nidulans strain conditional for calmodulin expression reveals that this
      protein is required during G1/S and for the initiation of mitosis. A lack of
      calmodulin results in cell cycle arrest, and a failure in polar growth that
      accompanies germination of A nidulans spores. In addition, increased expression
      of calmodulin in this organism permits growth at suboptimal calcium
      concentrations, indicating that cell growth is coordinately regulated by calcium
      and calmodulin. Together these results indicate that calmodulin-dependent
      processes may be conserved between A nidulans and vertebrate cells, and suggest
      that this approach may allow us to elucidate the molecular mechanism underlying
      calmodulin-regulated control of cell proliferation.

PMID- 1343600
TI  - Calcium regulation of immediate early gene transcription.
AB  - Cellular immediate early genes (IEGs) are a class of genes whose transcription is
      transiently activated within minutes of exposure of cells to a wide range of
      extracellular stimuli. In mature neurons IEG expression can be triggered by a
      variety of neutrotransmitters and neurotrophic factors. The IEGs, many of which
      encode transcription factors, are believed to control the physiological response
      of the cells to the initial stimulation event by activating secondary programs of
      gene expression. The mechanism by which membrane depolarization/Ca2+ influx
      trigger the activation of one IEG, c-fos, has been characterized in PC12 cells.
      In these cells, the cAMP response element-binding protein (CREB) functions as a
      Ca2+ regulated transcription factor. In addition, CREB is an in vitro substrate
      for several Ca2+ calmodulin-dependent protein kinases (CaM kinases). These
      results suggest a model whereby activation of voltage sensitive Ca2+ channels
      stimulates CaM kinase activation leading to CREB phosphorylation and c-fos
      transcriptional activation.

PMID- 1343601
TI  - Altered mechanical responses of malignant hyperthermic skeletal muscle during
      repetitive stimulation.
AB  - This investigation examined the mechanical responses of malignant hyperthermic
      (MH) and normal porcine skeletal muscle to repetitive stimulation. Twitch and
      maximal tetanic tensions were not significantly different between muscle types.
      Tensions produced during stimulation at 20-80 Hz were significantly less in MH
      muscle than in normal muscle. In addition, MH muscle showed significantly greater
      force decline (tetanic fade) at the end of contractions evoked by 20-80 Hz
      stimulation. When stimulated to fatigue, both normal and MH muscle exhibited
      similar rates of tension decline during the initial minutes. Further stimulation
      caused additional decline in normal muscle, but a tension plateau in MH muscle.
      In all cases, normal muscle had greater magnitudes of fatigue than did MH muscle.
      Results show that there are marked differences between MH and normal muscle in
      the mechanical responses to repetitive stimulation. Due to its inability to
      properly regulate intracellular Ca2+ exchange, it is possible that MH muscle
      might be a useful tool for identifying the mechanisms of muscle fatigue in normal
      muscle.

PMID- 1343603
TI  - Characterization of cultured rat aortic endothelial cells.
AB  - We describe a new method to obtain rat aortic endothelial cells without
      contamination by vascular smooth muscle cells. The endothelial cells were
      characterized up to the 20th passage by low density lipoprotein incorporation,
      the absence of alpha-smooth muscle actin, the production of endothelium derived
      relaxing factor, and an elevation in intracellular free calcium concentration in
      response to bradykinin and ATP but not to AMP and angiotensin II.

PMID- 1343602
TI  - Atrial natriuretic peptide during water deprivation or hemorrhage in rats.
      Relationship with arginine vasopressin and osmolarity.
AB  - The concentrations of atrial natriuretic peptide (ANP) in atria, hypothalami and
      plasma were investigated in relation to the variations of the plasma endogenous
      immunoreactive arginine vasopressin (Ir-AVP) during water deprivation or
      hemorrhage in normal conscious Wistar rats. Furthermore, the in vitro and in vivo
      effect of extracellular hyperosmolarity on ANP release from right atrium and
      hypothalamus was examined. Water deprivation elevated circulating immunoreactive
      ANP (Ir-ANP: pg/ml) to 153 +/- 7 (24 h); 174 +/- 1 (48 h) from the control level
      (109.6 +/- 7.8). This increase in Ir-ANP concentration which correlated with
      atrial (r = -0.93) or hypothalamic (r = -0.87) Ir-ANP content decrease, was
      associated with significantly enhanced levels of plasma Ir-AVP, plasma sodium,
      osmolarity and hematocrit. An acute volume depletion by hemorrhage significantly
      reduced plasma Ir-ANP (67 +/- 8.4 pg/ml) from the sham operated level (140 +/- 18
      pg/ml). Plasma Ir-AVP was elevated dramatically (207.4 +/- 53.4 pg/ml) compared
      with the sham operated level (8.8 +/- 2.6 pg/ml). These results, indicating the
      lack of correlation between plasma Ir-ANP and Ir-AVP in vivo, suggest that the
      ANP secretion, which is regulated mainly by plasma volume, may be modulated by a
      change in plasma osmolarity. Extracellular hyperosmolarity stimulated the ANP
      release from superfused sliced normal rat atria and hypothalami.

PMID- 1343604
TI  - Agonist-induced production of inositol phosphates in human airway smooth muscle
      cells in culture.
AB  - Smooth muscle cells (SMC) from human bronchi were isolated by elastase treatment,
      subcultured, and characterized by their positive reaction with a monoclonal
      antibody against alpha-smooth muscle actin (alpha SMA). In each cell line tested,
      at least 95% of the cells were positively stained. The functional properties of
      these cells were examined by measuring the metabolism of inositol phosphates
      (IPs). For that purpose, cells were incubated for 3 days before reaching
      confluency in the presence of myo-[3H]inositol in order to label the
      phosphoinositide pool, and the various [3H]IPs were separated by HPLC on a SAX
      column with a phosphate gradient. IP1 isomers were separated in three peaks; IP2,
      IP3, IP4, IP5 and IP6 (phytic acid) were each eluted as single peaks. The
      identity of the [3H]peaks was verified with corresponding [3H]IP standards. The
      accumulation of [3H]IPs was measured by incubating cells up to 30 min in the
      presence of 10 mM LiCl, with or without a bronchoconstrictor agent (carbachol,
      histamine, PGF2 alpha). Histamine, 10(-4) M, elicited a four times larger IP
      accumulation than carbachol, 10(-4) M, and than PGF2 alpha, 5 10(-5) M. Dose
      response curves were established for histamine and carbachol in the range 10(-7)
      10(-4) M. At 10(-7) M, carbachol was more effective than histamine in stimulating
      the IP metabolism. Atropine blocked the response to carbachol, and
      diphenhydramine inhibited the effect of histamine, indicating the specificity of
      the response to the agonists. These results indicate that cultured human
      bronchial SMC are a suitable preparation for studying physiological aspects of
      membrane transduction in the airways.

PMID- 1343605
TI  - Rat liver response elicited by long-term cold exposure.
AB  - We measured mitochondrial protein mass as well as State 4 and 3 respiratory rates
      using different substrates in isolated liver mitochondria from 30-day cold
      exposed rats. In addition, we measured the respiration under different conditions
      of stimulation in isolated hepatocytes from long-term cold-exposed rats. The
      results show that long-term cold exposure elicits a significant increase in
      hepatic mass and mitochondrial protein mass. No variation was found in oxygen
      consumption of isolated mitochondria and hepatocytes. On the whole, the results
      indicate that long-term exposure elicits an increase in hepatic mitochondrial
      protein mass but not in hepatic oxygen consumption.

PMID- 1343606
TI  - Does episiotomy prevent perineal trauma and pelvic floor relaxation?
AB  - OBJECTIVE: To compare the outcomes of the current practice of liberally or
      routinely employing episiotomy to prevent perineal tears and pelvic floor
      relaxation (control group) to a policy of restricting episiotomy use to specific
      fetal and maternal indications (experimental group). DESIGN: A randomized
      controlled trial (RCT). SETTING: Three university hospitals in Montreal.
      SUBJECTS: Seven hundred three low-risk women enrolled at 30 to 34 weeks of
      gestation were randomized late in labor to the designated trial arm, by parity,
      and followed up to 3 months postpartum. MAIN OUTCOME MEASURES: Antepartum and
      postpartum information on perineal trauma and pain, pelvic floor symptoms
      (urinary incontinence), and sexual activity was collected through the use of
      standard questionnaires; pelvic floor function was measured by electromyographic
      (EMG) perineometry. RESULTS: Restricting episiotomy use in primiparous women was
      associated with similar sutured perineal trauma to the liberal or routine
      approach. Multiparous women in the restricted episiotomy group more often gave
      birth with an intact perineum (31% compared with 19%, odds ratio (OR) = 1.85, 95%
      confidence interval (CI) = 1.09 to 3.16). All but one 3rd/4th-degree perineal
      tear was associated with median episiotomy (46 of 47 in primiparous women and 6
      of 6 among multiparous women). No difference between trial groups was found in
      postpartum perineal pain, antepartum and 3-month postpartum EMG perineometry, and
      urinary and pelvic floor symptoms. CONCLUSIONS: We found no evidence that liberal
      or routine use of episiotomy prevents perineal trauma or pelvic floor relaxation.
      Virtually all severe perineal trauma was associated with median episiotomy.
      Restriction of episiotomy use among multiparous women resulted in significantly
      more intact perineums and less perineal suturing.

PMID- 1343607
TI  - Will publication bias vanish in the age of online journals?
AB  - A major advantage of online journals, in contrast to printed journals, is that
      lack of space is not an obstacle. One obvious benefit of this is the ability to
      include material that might help clarify or emphasize important points, but that
      might not be considered essential in the context of the limited space available
      in a printed journal. A more important benefit of removing space constraints is
      the potential to eliminate publication bias. This bias occurs when a study is not
      published because it fails to find any statistically significant differences or
      associations. While authors play a major role in generating this bias, their
      belief that publication depends on statistical significance has some foundation
      in the existing printed literature. Nevertheless, realizing the potential to
      eliminate publication bias depends largely on the willingness of authors to
      submit their work. The Online Journal of Current Clinical Trials will judge
      papers on the quality of the work and the importance of the findings, not on the
      level of statistical significance achieved in any comparisons made. Valuable
      papers need no longer be turned away simply because of lack of space.

PMID- 1343608
TI  - A clinical trials database as a research tool in health care.
AB  - OBJECTIVE: The rapid, efficient, and accurate communication of clinical research
      findings to both clinicians and researchers is essential to the process of
      improving medical care. This information should be conveyed in a form that
      facilitates the interpretation of the complete body of research on a specific
      condition. Unfortunately, the prevailing system for dissemination of clinical
      research fails to meet these criteria. This paper proposes a system for
      cataloging clinical trials and communicating their results in a comprehensive and
      comprehensible format. METHOD: The system involves the use of a hierarchical
      matrix structure that allows for the selection and evaluation of related groups
      of clinical trials. The format of the data is tailored to the requirements of
      metaanalysis. RESULTS: An example is presented using the treatment of acute
      Crohn's disease and including a sample metaanalysis of immunosuppressive therapy
      for this condition. CONCLUSIONS: The hierarchical matrix structure in conjunction
      with a comprehensive database of clinical trials holds the potential to
      facilitate access to and interpretation of clinical research.

PMID- 1343609
TI  - Trimethoprim-sulfamethoxazole compared with ciprofloxacin for the prevention of
      urinary tract infection in renal transplant recipients. A double-blind,
      randomized controlled trial.
AB  - BACKGROUND: Prophylaxis with low-dose trimethoprim-sulfamethoxazole has been
      shown to be cost-effective in the prevention of urinary tract infections,
      pyelonephritis, urosepsis, and pneumocystis pneumonia in renal transplant
      recipients. Ciprofloxacin, effective against almost all urinary tract pathogens
      in this patient population, represents a promising alternative prophylactic agent
      for patients unable to tolerate trimethoprim-sulfamethoxazole due to toxicity.
      METHODS: We conducted a randomized, double-blind trial to compare low-dose
      trimethoprim-sulfamethoxazole with ciprofloxacin for the prevention of urinary
      tract infections in renal transplant recipients. Patients received either
      ciprofloxacin (250 mg) or trimethoprim-sulfamethoxazole (80 mg trimethoprim, 400
      mg sulfamethoxazole) daily for 6 months following transplantation. Treatment was
      considered successful if patients completed the 6-month course and 3-month follow
      up period without evidence of urinary tract infection or drug-related toxicities.
      RESULTS: Of 103 eligible patients, 51 received ciprofloxacin and 52 received
      trimethoprim-sulfamethoxazole. At 6 months, treatment was successful in 75% (38
      of 51) receiving ciprofloxacin and 71% (37 of 52) treated with trimethoprim
      sulfamethoxazole (P = 0.87, relative risk 1.04, 95% confidence limits 0.83 to
      1.33). Thirteen patients (25%) receiving trimethoprim-sulfamethoxazole withdrew
      from the study-4 for resistant urinary tract infection and 9 for drug-related
      toxicity, while 3 (6%) of the patients receiving ciprofloxacin withdrew because
      of drug-related toxicity (P = 0.016, relative risk of urinary tract infection or
      adverse event 0.24, 95% confidence limits 0.07 to 0.78). At 9 months, all 38
      patients who completed the 6-month course of ciprofloxacin remained free of
      urinary tract infection, while an additional 4 patients who had received
      trimethoprim-sulfamethoxazole prophylaxis (total of 8 patients over the 9 months)
      developed urinary tract infections (P = 0.006, Fisher's exact test for urinary
      tract infection alone). Pneumocystis pneumonia occurred in a total of 7 (14%)
      patients who were randomized to ciprofloxacin, but 2 of the 7 had withdrawn from
      the study at least 2 weeks prior to the diagnosis of pneumocystis pneumonia.
      There were no cases of pneumocystis pneumonia in patients receiving trimethoprim
      sulfamethoxazole (P = 0.006). Following completion of the study, monthly
      aerosolized pentamidine administered in conjunction with ciprofloxacin has
      provided complete protection against urinary tract infection and pneumocystis
      pneumonia in 30 transplant recipients unable to tolerate trimethoprim
      sulfamethoxazole therapy. CONCLUSIONS: Ciprofloxacin is at least as effective as
      trimethoprim-sulfamethoxazole in the prevention of urinary tract infection in
      renal transplant recipients, and is better tolerated. Ciprofloxacin prophylaxis
      is associated with a higher incidence of pneumocystis pneumonia than is
      trimethoprim-sulfamethoxazole therapy. An uncontrolled follow-up study suggests
      that ciprofloxacin prophylaxis combined with monthly aerosolized pentamidine may
      be efficacious in preventing both urinary tract infection and pneumocystis
      pneumonia in renal transplant recipients.

PMID- 1343610
TI  - Episiotomy. To cut or not to cut?
AB  - Episiotomy is performed in over half of the hospital-based deliveries in the US,
      despite the dearth of scientific data demonstrating its usefulness in
      uncomplicated cases. After roughly 70 years of widespread use in the US, the
      first randomized clinical trial of episiotomy conducted in North America (and the
      first worldwide involving median episiotomy) found no evidence for better
      outcomes in deliveries assigned to "liberal" than those assigned to "restricted"
      use of episiotomy. These results lend support to the many health professionals
      and lay persons calling for further reduction in the use of this procedure.

PMID- 1343611
TI  - Low-dose (7.5 mg) oral methotrexate for chronic progressive multiple sclerosis.
      Design of a randomized, placebo-controlled trial with sample size benefits from a
      composite outcome variable including preliminary data on toxicity.
AB  - OBJECTIVE: To present a detailed description of (1) the study design of this
      ongoing trial, (2) advantages of using a composite outcome variable instead of
      multiple individual outcome measures, (3) treatment group characteristics at
      baseline, and (4) observed short-term methotrexate (MTX) toxicity. DESIGN:
      Randomized, double-masked, placebo-controlled intervention study. SETTING:
      Referral-based outpatient multidisciplinary multiple sclerosis (MS) clinic.
      PATIENTS: Participation offered to all clinically definite chronic progressive
      multiple sclerosis (CPMS) patients attending clinic ages 21 to 60, disease
      duration > 1 year, Expanded Disability Status Scale (EDSS) score 3.0 to 6.5
      (ambulatory with moderate disability). Patients first stratified by EDSS 3.0 to
      5.5 and 6.0 to 6.5, then randomized to MTX or placebo treatment. INTERVENTION:
      Weekly oral low-dose (7.5 mg) MTX or identical-appearing placebo for 2 years
      followed by a 1-year observation period. MAIN OUTCOME MEASURES: Sample size
      calculations undertaken prior to enrolling patients based upon a composite
      outcome variable consisting of designated change in any of the following
      functional measures: (1) EDSS, (2) Ambulation Index (AI), (3) Box and Block Test
      (BBT), and (4) 9-Hole Peg Test (9HPT). RESULTS: (1) Treatment group
      characteristics were comparable at baseline, (2) no patient has been withdrawn
      for adverse effects or lost to follow-up, (3) no significant short-term MTX
      toxicity has been observed. CONCLUSIONS: (1) The use of a composite outcome
      measure in the design of MS clinical trials is a promising alternative to
      multiple individual outcome measures that are relatively insensitive to detecting
      clinical change, (2) low-dose oral weekly MTX does not appear to be associated
      with significant short-term toxicity in CPMS. Conclusions regarding therapeutic
      efficacy of MTX in MS must await completion of this clinical trial.

PMID- 1343612
TI  - Analgesia for the reduction of Colles fracture. A comparison of hematoma block
      and intravenous sedation.
AB  - OBJECTIVE: An alternative to general anesthesia was tested against conventional
      sedation by a double-blind, randomized clinical trial in reduction of Colles
      fracture. SETTINGS: A large teaching hospital where cases of Colles fracture are
      not different from those seen in district hospitals. PATIENTS: Sixty-six out of
      80 consecutive cases with this fracture were selected from March to August 1990
      on the basis of: 1) informed consent; 2) no contraindication to any method of
      analgesia; 3) no analgesic during the past 8 hours; 4) injury duration less than
      96 hours; 5) no mental, auditory, or visual impairment; and 6) no associated
      injury. INTERVENTIONS: Patients were randomized into 2 equal groups. After tests
      for Xylocaine (Astra brand of lidocaine hydrochloride) sensitivity in both
      groups, the A group received 30 mg of pentazocine with 5 mg of diazepam
      intravenously on the dorsum of the affected wrist (sedation group), whereas the B
      group received 20 cc of 1.5% Xylocaine into the fracture hematoma. Five minutes
      later the fracture was reduced and immobilized by Lakhtakia or A. Singh. MAIN
      OUTCOME MEASURES: Thirteen to 15 hours later Manglik, blinded to the analgesia
      status of the patient, recorded pain before, during, and after reduction using
      Visual Analogue Scale (VAS). MAIN RESULTS: Statistically, randomization and
      blinding were found to be effective. The pain scores during reduction in the
      local anesthetic group (median = 1.8) were significantly less than those in the
      sedation group (median = 8.7), P < 0.001 using the Wilcoxon rank sum test. The
      difference persisted in regression analysis. The 2 methods proved comparable in
      safety and other measures of effectiveness. CONCLUSIONS: Hematoma block by local
      anesthetic is a safe and effective alternative to sedation in reduction of Colles
      fracture.

PMID- 1343613
TI  - The Monitored Atherosclerosis Regression Study (MARS). Design, methods and
      baseline results.
AB  - OBJECTIVE: The Monitored Atherosclerosis Regression Study (MARS) was designed to
      evaluate the effect of cholesterol lowering by monotherapy with an HMG-CoA
      reductase inhibitor on progression/regression of atherosclerosis in subjects with
      angiographically documented coronary artery disease. The purpose of this paper is
      to present the design, methods, and baseline results of MARS. DESIGN: MARS is a
      prospective, randomized, double-blind, placebo-controlled trial with baseline, 2
      year, and 4-year coronary angiography as well as carotid, brachial, and popliteal
      ultrasonography. SETTING: Outpatient clinics at the University of Southern
      California School of Medicine and the University of Wisconsin School of Medicine.
      SUBJECTS: Two hundred seventy participants of both sexes were recruited directly
      from the cardiac catheterization laboratory or by chart review of patients having
      undergone cardiac catheterization in the past. Subjects were considered eligible
      if they had angiographically demonstrable atherosclerosis in 2 or more coronary
      artery segments, unaltered by angioplasty, with at least 1 lesion > or = 50% but
      < 100% diameter stenosis (%S). The inclusion range for total cholesterol (TC) was
      between 190 and 295 mg/dL. Exclusion factors were: triglycerides > or = 500
      mg/dL; premenopausal females; uncontrolled hypertension; diabetes mellitus;
      untreated thyroid disease; liver dysfunction; renal insufficiency; congestive
      heart failure; major arrhythmia; left ventricular conduction defects; or any life
      threatening disease. INTERVENTION: Subjects were placed on a low-fat, low
      cholesterol diet and either 40 mg b.i.d. lovastatin (Mevacor) or placebo.
      Randomization was stratified by sex, smoking status, and TC. MAIN OUTCOME
      MEASURES: Per-subject average change in %S as determined by quantitative coronary
      angiography (QCA) is the primary angiographic endpoint. Secondary endpoints are:
      categorical analyses of the proportion of subjects with progression; human panel
      reading of coronary angiograms; and change in minimum lumen diameter (MLD) in mm
      by QCA. Carotid, brachial, and popliteal ultrasonography is also being performed.
      RESULTS: The subjects randomized into MARS are 91.5% male with an age range of 37
      to 67 years (mean age 57.9 years). For the cohort, baseline lipids are (mean +/-
      SD): TC, 231 +/- 24 mg/dL; low-density lipoprotein cholesterol (LDL-C) by
      ultracentrifugation, 153 +/- 24 mg/dL; LDL-C, by calculation, 157 +/- 23 mg/dL;
      high-density lipoprotein cholesterol (HDL-C), 43 +/- 10 mg/dL; and triglycerides,
      160 +/- 73 mg/dL. There were no significant differences between treatment groups
      in baseline lipid levels or baseline angiographic characteristics. CONCLUSIONS:
      MARS baseline data show adequacy of randomization with comparability of
      lovastatin and placebo groups in demographic, lipid, and angiographic
      characteristics.

PMID- 1343615
TI  - Is the medical world ready for electronic journals?
AB  - New technologies offer new ways to deliver scholarly information, perhaps
      advantageously compared with paper journals, which have been an accustomed mode
      of scholarly communication for 300 years. Paper journals offer conveniences in
      handling and reading, and the economic constraints on their length tend to ensure
      that this constraint is important. Electronic journals are not yet as easy to
      use. But paper journals are economically cost effective and these space
      constraints prevent their publishing information not important to most readers
      but important to some. Electronic journals offer new advantages for readers,
      including the capacity to carry more and longer papers, linkages between related
      documents, and hypertext functions. The editors of The Online Journal of Current
      Clinical Trials welcome comments on its features and content; these should be
      sent to Dr. Maria L. Lebron, Managing Editor, CCT, AAAS, 1333 H Street, NW,
      Washington, DC 20005 USA, FAX 202-842-2868.

PMID- 1343614
TI  - Early or selective surfactant (colfosceril palmitate, Exosurf) for intubated
      babies at 26 to 29 weeks gestation. A European double-blind trial with sequential
      analysis. European Exosurf Study Group.
AB  - OBJECTIVE: To compare a policy of giving surfactant to all intubated babies of
      gestational age 26 to 29 weeks with a policy of treating only those babies
      developing respiratory distress syndrome (RDS). DESIGN: Randomized, double-blind,
      placebo-controlled. SETTING: Twenty-two neonatal intensive care units in 5
      countries. INTERVENTIONS: Blinded administration of either surfactant
      (colfosceril palmitate, Exosurf) or air placebo, within 2 hours of birth. Babies
      in either group developing RDS during the following 18 hours received 2 unblinded
      doses of surfactant 12 hours apart. Babies without RDS received a 2nd dose of
      surfactant or air as originally randomized 18 hours after the 1st dose. OUTCOME
      MEASURES: Primary: survival to 28 days without brain damage (cysts or
      hydrocephalus-blinded ultrasound assessment with central review). Secondary:
      incidence of RDS; durations of intubation, intensive care, and oxygen therapy.
      SAFETY: incidences of pneumothorax, pulmonary interstitial emphysema, persistent
      ductus arteriosus, infection, and necrotizing enterocolitis. RESULTS: Two hundred
      twelve babies randomized to early and 208 to selective surfactant. One hundred
      five early babies and 142 selective babies developed RDS requiring unblinded
      surfactant (50% versus 68%; 95% CI of difference, 9% to 27%). At age 28 days, 175
      early and 163 selective babies survived (83% versus 78%, 95% CI, -3% to 12%), 140
      early and 131 selective without brain damage (66% versus 63%, 95% CI, -6% to 12%,
      P = 0.41). Significant reductions were seen in the incidence of pneumothorax (18%
      early versus 26% selective) and pulmonary interstitial emphysema (14% versus 22%)
      (95% CI for both, 1% to 16%). CONCLUSIONS: Early surfactant reduces short-term
      morbidity, but any difference in outcome at 28 days is likely to be small.

PMID- 1343616
TI  - The publisher's perspective.
AB  - The Online Journal of Current Clinical Trials (CCT) represents a publishing
      milestone in the history of the American Association for the Advancement of
      Science. The historical background and institutional considerations leading to
      the establishment of CCT are discussed in this editorial.

PMID- 1343617
TI  - Intensive therapy with cisplatin, interleukin-2 and interferon-alpha-2a in
      patients with metastatic melanoma. A phase II Study.
AB  - OBJECTIVE: Based upon their individual clinical activity and combined effects in
      animal models or in vitro, we wished to evaluate a regimen of cisplatin,
      interferon-alpha, and IL-2 in patients with metastatic melanoma. DESIGN: Phase II
      pilot study. SETTING: Referral-based US Government clinical research unit.
      PATIENTS: Nine patients with metastatic malignant melanoma. INTERVENTION:
      Cisplatin 75-100 mg/m2 was administered intravenously over 30 minutes on days 1
      and 8. Interferon-alpha 2a 5 Mu/m2 body surface area (BSA) was given
      subcutaneously for 4 days beginning 1 day before each dose of cisplatin.
      Beginning on day 15 and day 22, IL-2 was administered by intravenous continuous
      infusion at 3 Mu/m2 BSA/d for 96 hours and by daily intravenous bolus concurrent
      with daily subcutaneous doses of interferon-alpha 2a. MAIN OUTCOME MEASURES:
      Antitumor response and toxicities. RESULTS: The study was stopped due to renal
      and hematopoietic toxicity and severe, delayed nausea and vomiting associated
      with the cisplatin-interferon treatment. Three of 9 patients achieved a partial
      response (duration 2.5, 4, 14+ months), and an additional patient had a 50%
      reduction in measurable tumor volume before undergoing resection of residual
      disease. Overall response rate was 45%. CONCLUSION: This regimen was associated
      with excessive toxicity, and the lack of complete responses in a patient cohort
      with favorable characteristics for response (good performance status,
      predominance of skin and lymph node metastatic sites) suggests that it had no
      advantage over less toxic treatment regimens. REGISTRATION: National Cancer
      Institute/Cancer Therapy Evaluation Program T89-0137.

PMID- 1343618
TI  - Developmental theories for the 1990s: development and individual differences.
AB  - Understanding both typical human development and indivdual differences within the
      same theoretical framework has been difficult because the 2 orientations arise
      from different philosophical traditions. It is argued that an evolutionary
      perspective can unite the study of both species-typical development and
      individual variation. Research on determininants of development from many
      perspectives can be understood within an evolutionary framework in which organism
      and environment combine to produce development. Species-normal genes and
      environments and indidividual variations in genes and environments both affect
      personality, social, and intellectual development. These domains are used as
      examples to integrate theories of normal development and individual differences.
      Within the usual samples of European, North American, and developed Asian
      countries, the results of family and twin studies show that environments within
      the normal species range are crucial to normal development. Given a wide range of
      environmental opportunities and emotional supports, however, most children in
      these societies grow up to be individually different based on their individual
      genotypes. Understanding the ways in which genes and environments work together
      helps developmentalists to identify children in need of intervention and to
      tailor interventions to their particular needs.

PMID- 1343619
TI  - Salivary excretion of drugs in children: theoretical and practical issues in
      therapeutic drug monitoring.
AB  - Studies suggest that saliva could be used instead of blood in the therapeutic
      monitoring of many drugs. This has distinct advantages in pediatrics and
      neonatology as saliva sampling is painless and spares blood. Stimulation of
      saliva secretion with a chemical stimulus (i.e. citric acid applied over the
      tongue) facilitates the study of younger patients. Secretory and reabsorptive
      processes which take place in the ductal system of the salivary glands, and the
      rate of flow of the secretion play major roles in the determination of the
      concentration of solutes in saliva. Drug passage into saliva follows the general
      principles of movement of drugs across biologic membranes. Only the unbound
      fraction of the drug in plasma is available for diffusion into saliva and a
      relationship exists between saliva pH and the saliva/plasma concentration ratio
      of many polar drugs (tolbutamide, propranolol, procainamide, etc.). However,
      deviations from the pH theory exist and the inter -and intra-individual
      variations in saliva/plasma concentration ratios of salicylate and procainamide
      cannot be explained solely on the basis of fluctuations of salivary pH; on the
      other hand, a useful relationship exists between plasma and saliva phenobarbital
      concentrations with no need to correct for saliva pH. The use of stimulated
      saliva has several advantages over resting saliva: a larger volume of the sample
      is obtained, the pH gradient between plasma and saliva is smaller, the
      variability in saliva/plasma concentration ratios of some drugs is narrowed, and
      less specimens are too viscous or discolored to allow drug analysis. Thorough
      rinsing of the mouth is required prior to saliva sampling as remnants of orally
      administered medicines may contaminate saliva specimens and give spuriously high
      values. Deviation from a simple but strict methodology accounts for some of the
      discrepancies found in the literature. Studies in children uniformly recommend
      saliva for therapeutic monitoring of phenytoin, carbamazepine and phenobarbital.
      Saliva sampling for therapeutic monitoring of ethosuximide, primidone and digoxin
      in infants and children, and of theophylline and caffeine in the neonate is
      promising, but little pediatric experience is available as yet. The value of
      saliva in therapeutic monitoring of theophylline in children is still
      controversial. Little of highly polar compounds such as aminoglycosides, and of
      polar highly protein bound drugs such as valproic acid is present in saliva. More
      data are still needed on the excretion of drugs in saliva in infants and in
      acutely ill children, and few data exist in the premature and full-term neonate.

PMID- 1343620
TI  - Prophylactic low-dose vancomycin treatment in very-low-birth-weight infants.
AB  - For the prophylaxis of septicemia with coagulase-negative staphylococci in a high
      risk very-low-birth-weight population, we administered 5 mg/kg of vancomycin
      every 12 h. Distribution volume and half-life of vancomycin were determined.
      Serum peak and trough levels were obtained on day 3 of treatment. With this low
      dose regimen, serum concentrations in the therapeutic range were achieved in 35
      of the 45 patients. Distribution volume and half-life were 0.692 liters/kg and
      7.4 h, respectively. The distribution volume was not related to the gestational
      age; the half-life in the group of patients with a gestational age < 30 weeks was
      considerably higher. The 10 small-for-gestational-age children had a
      significantly smaller distribution volume. The vancomycin trough levels
      correlated with the serum creatinine concentrations and, therefore, with the
      gestational age. Our study indicates that this low vancomycin dose is sufficient
      in very-low-birth-weight infants to achieve therapeutic serum levels, being
      suitable for both prophylaxis and sepsis therapy.

PMID- 1343621
TI  - Methamphetamine detection from meconium and amniotic fluid in guinea pigs depends
      on gestational age and metabolism.
AB  - Significant adverse perinatal effects of maternal methamphetamine use have been
      reported, but little is known about factors influencing methamphetamine screening
      test results during the perinatal period. We tested the hypothesis that
      gestational age would affect quantitative recovery of methamphetamine in meconium
      and amniotic fluid. Time-bred guinea pigs received an intraperitoneal (i.p.)
      injection of 1 mg/kg methamphetamine at either 44 days (0.65 of term, n = 5), 50
      days (0.74, n = 8), 56 days (0.82, n = 9) or 63 days (0.93, n = 4) gestation. At
      1 or 7 days after i.p. methamphetamine, meconium and amniotic fluid were
      collected for quantitative methamphetamine assay by gas chromatography-mass
      spectrometry. Recovery from amniotic fluid and meconium 1 day after injection was
      influenced by gestational age. Greater values in amniotic fluid and meconium and
      a higher percentage of positive samples were seen in older fetuses. Collectively
      at all gestational ages, combined testing of amniotic fluid and meconium yielded
      detectable methamphetamine or its metabolites in 87% of guinea pigs 1 day after
      injection. However, methamphetamine was not detectable 1 week after injection in
      any sample (n = 63) at either 0.74 or 0.82 of term except for one positive
      amniotic fluid sample. Finally, demethylation of methamphetamine to amphetamine
      was higher in older fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343622
TI  - The valproic acid metabolite E-2-n-propyl-2-pentenoic acid does not induce spina
      bifida in the mouse.
AB  - The antiepileptic drug valproic acid (VPA) has been implicated as a human
      teratogen causing spina bifida aperta. Recently we developed a mouse model
      inducing spina bifida aperta and occulta with VPA. In a search for novel
      antiepileptic agents the VPA metabolite E-2-n-propyl-2-pentenoic acid (2-en-VPA)
      had been developed. In the mouse, 2-en-VPA exhibits anticonvulsive potency
      similar to VPA but very low teratogenic potency (induction of exencephaly). We
      have now compared VPA and its metabolite 2-en-VPA in regard to induction of spina
      bifida in our mouse model. 2-en-VPA was administered 3 times during the period of
      gestation most sensitive for the induction of spina bifida aperta with VPA: on
      day 9 of gestation at 0, 6 and 12 h. The following doses were injected (in mmol 2
      en-VPA-Na/kg): (a) 3 x 2.1, (b) 3 x 2.7 (the equimolar dose of VPA is the
      threshold dose for induction of spina bifida aperta) and (c) 3 x 3.0 (the
      equimolar VPA dose produced spina bifida aperta). 2-en-VPA did not induce spina
      bifida aperta in the mouse in any of these groups. We then investigated the
      induction of spina bifida occulta in the three dose groups. Spina bifida occulta
      is a less serious form of spina bifida and may provide a sensitive method to
      estimate the potency of a compound to induce more severe forms of spina bifida.
      This malformation was demonstrated in alcian-blue- and alizarin-red-stained fetal
      skeletons by measurements of the distance between the cartilaginous ends of each
      vertebral arch.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343623
TI  - [The functional significance of coronary collateral circulation during sudden
      coronary occlusion].
AB  - The functional significance of the coronary collateral circulation remains
      controversial. It has been suggested that collateral circulation possibly helps
      prevent myocardial ischemia. Seventeen target lesions in 15 patients were studied
      to determine the relationship between the extent of the coronary collateral
      circulation and the degree of ventricular dysfunction during percutaneous
      transluminal coronary angioplasty (PTCA). During the first balloon inflation,
      diastolic indices such as left ventricular end-diastolic pressure, max negative
      dP/dt and the time constant of early relaxation were measured immediately before
      and at 60 sec following balloon inflation. During the second inflation, the
      contralateral and ipsilateral collateral circulations were evaluated. The latter
      was graded as follows: 0 = none; I = filling of side branches only; II = partial
      filling of the epicardial segment; and III = complete filling of the epicardial
      segment. Following balloon inflation, a significant increase was noted in the
      time constant of early relaxation in patients with grade 0 collateral circulation
      (40 +/- 7 to 47 +/- 7 msec: p < 0.01) and grade II collateral circulation (52 +/-
      12 to 56 +/- 13 msec: p < 0.05). The percent increase in the time constant of
      early relaxation of patients with grade 0 and I collateral circulations exceeded
      that of patients with grade II (p < 0.05) or grade III collateral circulation (p
      < 0.05). Left ventricular end-diastolic pressure was elevated in all groups
      during PTCA. There was no significant difference in the percent increase of left
      ventricular end-diastolic pressure (LVEDP) between the 4 groups. However, LVEDP
      before PTCA was higher in patients with grade III collateral circulation than in
      patients in the other groups. Max negative dP/dt did not change significantly in
      any group. In conclusion, collateral circulation helps prevent myocardial
      ischemia during acute coronary occlusion, which is most precisely shown by the
      time constant of early relaxation. The degree of this protective function of
      collateral circulation seems to vary.

PMID- 1343624
TI  - [Clinical characteristics of pulmonary edema in patients with unstable angina].
AB  - To elucidate the clinical characteristics of pulmonary edema in unstable angina,
      120 patients with unstable angina who admitted to the hospital within 6 hours
      after the onset of chest pain were studied. The criteria for the diagnosis of
      pulmonary edema included interstitial pulmonary edema and diffuse alveolar edema.
      Pulmonary edema was present in 24 patients. In these patients, the duration of
      chest pain was relatively longer, and the incidences of diabetes mellitus,
      emergency coronary revascularization and multiple-vessel coronary artery disease
      were higher than in those without pulmonary edema. In addition, in-hospital
      mortality rate in patients with pulmonary edema was higher than in those without
      it (21 vs 1%, p < 0.001), which is probably due to a large area of myocardial
      ischemia. For these patients, therefore, early diagnosis and appropriate therapy
      to save viable segments of the myocardium are mandatory.

PMID- 1343625
TI  - Left atrial function in ischemic heart disease assessed by intravenous digital
      subtraction angiography.
AB  - To investigate changes in left atrial morphology and dimensions during the
      cardiac cycle, the atrium was visualized by intravenous digital subtraction
      angiography (DSA). The study subjects consisted of 22 male patients whose average
      age was 54.5 +/- 8.6 years. They had ischemic heart disease without mitral valve
      disease and were in sinus rhythm. They were 11 patients with old myocardial
      infarction (OMI group) and 11 who had chest pain without evidence of infarction
      (AP group). DSA was performed in the continuous mode. Contrast material (35 ml)
      was injected at a rate of 18 ml/sec via a catheter in the superior vena cava and
      subtraction images were obtained at a speed of 30 frames/sec in the right
      anterior oblique projection. The left atrial and left ventricular margins were
      traced manually, their areas were calculated, and fractional changes in area were
      analyzed. The left ventricular ejection fraction (LVEF) was calculated by
      densitometry. Cardiac catheterization was performed in 16 patients and the left
      ventricular end-diastolic pressure (LVEDP) and mean pulmonary arterial wedge
      pressure (PAWP) were measured. The entire left atrium was clearly imaged using
      DSA. Phase analysis of the time-area curves in the right anterior oblique
      projection revealed that the left atrial area was maximal during left ventricular
      end-systole (%LA1 = 100%), it decreased during early left ventricular diastole
      (%LA2), and then increased slightly again during mid-diastole (%LA3). After left
      atrial contraction, the minimum area was obtained (%LA4). The left atrium showed
      a two-stage decrease in the area due to passive emptying and active contraction
      during left ventricular diastole. Passive emptying (%LA1-%LA2) was significantly
      less in the OMI group than in the AP group (6.3 +/- 3.6 vs 13.3 +/- 4.8%, p <
      0.01, respectively). In all 22 subjects, passive emptying correlated with LVEF (r
      = 0.70, p < 0.001) and LVEDP (r = -0.58, p < 0.05). There was no difference in
      active contraction (%LA3-%LA4) between the 2 groups (26.0 +/- 5.7% in the OMI
      group, 28.2 +/- 8.4% in the AP group), and it did not correlate with LVEF or
      LVEDP. The ratio of passive emptying to active contraction [(%LA1-%LA2)/(%LA3
      %LA4)] correlated with LVEF (r = 0.63, p < 0.01). These findings suggested that
      impaired left ventricular diastolic function and a relative increase in atrial
      contraction were present in patients with a lower LVEF. The %LA4 correlated with
      LVEDP and PAWP (r = 0.65, r = 0.63, p < 0.01, respectively). In conclusion, DSA
      proved to be a useful method for investigating left atrial morphology and
      function.

PMID- 1343626
TI  - [Efficacy of intracoronary thrombolysis versus percutaneous transluminal coronary
      angioplasty for treating acute myocardial infarction].
AB  - The usefulness of percutaneous transluminal coronary angioplasty (PTCA) in
      patients with evolving myocardial infarction remains controversial. We
      retrospectively assessed the efficacy of PTCA on myocardial salvage in acute
      myocardial infarction in comparison with the efficacy of intracoronary
      thrombolysis (ICT). Sixty-two patients with initial anteroseptal myocardial
      infarction who had been treated within 6 hrs after the onset of chest pain were
      categorized into 4 groups: 1) spontaneous recanalization: n = 14, 2) successful
      PTCA: n = 25 (this group was further subdivided into 2 groups: direct PTCA group,
      primary PTCA without prior ICT: n = 19; and rescue PTCA group, PTCA after
      unsuccessful ICT: n = 6), 3) successful ICT group (n = 12), and 4) unsuccessful
      recanalization group (n = 11). Left ventricular function in the chronic phase was
      assessed by contrast ventriculography using the global ejection fraction (EF) and
      regional wall motion (RWM) was assessed by the centerline method. Patients with
      recanalization had a significantly higher EF than did those without (62 +/- 12 vs
      50 +/- 13%, p < 0.01). The mean EFs for groups with successful reperfusion were
      as follows: 65 +/- 8% for the spontaneous recanalization group, 61 +/- 14% for
      PTCA group (64 +/- 13% for direct PTCA group, 51 +/- 13% for rescue PTCA group)
      and 60 +/- 12% for the ICT group. The EFs for the spontaneous recanalization
      group and the direct PTCA group were significantly greater than that for the
      rescue PTCA group. The time to reperfusion and the thrombolysis in myocardial
      infarction (TIMI) flow grade before reperfusion did not affect the preservation
      of global left ventricular function. RWM of the infarcted area in patients with
      recanalization were less hypokinetic than that in patients without (p < 0.01).
      The mean RWM (SD/chord) in the successfully reperfused groups were -2.3 +/- 1.2
      for the spontaneous recanalization group, -2.6 +/- 1.2 for the PTCA group (-2.3
      +/- 1.1 for the direct PTCA group, -3.3 +/- 1.0 for rescue PTCA group) and -3.0
      +/- 0.5 for the ICT group. Hypokinesis of the infarcted area was more severe in
      the rescue PTCA group than in the spontaneous recanalization group and the direct
      PTCA group (multiple comparison test p < 0.01, respectively), and hypokinesis was
      more severe in the ICT group than in the direct PTCA group (Student's t-test, p <
      0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1343627
TI  - The effect of percutaneous transluminal coronary angioplasty on anaerobic
      threshold in patients with angina pectoris.
AB  - The anaerobic threshold (AT) is regarded an objective parameter for evaluating
      exercise tolerance, but its relationship to the improvement of myocardial
      ischemia remains uncertain. To investigate this relationship, submaximal
      treadmill exercise tests were performed for 15 consecutive patients with angina
      pectoris who had undergone successful percutaneous transluminal coronary
      angioplasty (PTCA). Before and after PTCA, the AT was determined using
      cardiorespiratory monitoring, while the patients were receiving their usual
      vasodilator medications. 1) Before PTCA, the minute oxygen uptake (VO2) at the AT
      correlated well with the peak VO2 (r = 0.92, p < 0.002). The VO2 at the AT,
      however, showed less correlation (r = 0.71, p < 0.002) with the VO2 at ST segment
      depression, while the latter parameter correlated closely with the peak VO2 (r =
      0.91, p < 0.002). 2) After PTCA, exercise time, peak VO2, and the double product
      at peak exercise increased significantly (from 640.1 +/- 212.2 to 772.9 +/- 230.0
      sec, p < 0.001, from 19.1 +/- 5.2 to 22.4 +/- 4.9 ml/min/kg, p < 0.05, and from
      19.7 +/- 5.0 x 10(3) to 23.7 +/- 4.5 x 10(3), p < 0.001, respectively). However,
      the VO2 at the AT did not increase significantly (from 15.8 +/- 4.1 to 16.6 +/-
      3.5 ml/min/kg, p = NS). The heart rate, systolic blood pressure, and double
      product at the AT did not change significantly. In conclusion, in patients with
      angina pectoris, the AT is apparently related to the onset of myocardial
      ischemia. However, the AT does not necessarily reflect acute improvement of
      myocardial ischemia immediately after PTCA.

PMID- 1343628
TI  - [Assessment of coronary artery bypass grafts by X-ray computed tomography with
      and without contrast enhancement].
AB  - To assess the patency of coronary artery bypass grafts, we tested the capability
      of X-ray computed tomography (CT) with and without contrast enhancement. This
      procedure was used on 63 grafts (30 in the LAD; 20 in the LCX; 13 in the RCA) in
      32 patients with a mean age of 56 +/- 8 years, all of whom were referred to our
      department for postoperative management or evaluation. The CT scanner used was
      Toshiba TCT-60A with a scan time of 3 sec, 5 mm thick slices, and 512 x 512
      pixels. CT scans without contrast enhancement were obtained from the level of the
      aortic arch to the left ventricle. Eight sec after 30 ml of contrast media was
      injected at a rate of 3 ml/sec into an antecubital vein, 5 scans were made at the
      same level of the pulmonary artery truncus. After positioning the regions of
      interests on the ascending aorta and grafts, we obtained time-density curves
      (TDCs) and compared the data with those recorded from an intraoperative
      electromagnetic flow meter (EMF). Fifty grafts were angiographically patent. The
      appearance time, build-up time, peak time, disappearance time and peak densities
      obtained from TDCs of grafts did not correlate with the flow volumes measured by
      EMF. Patent grafts were easily identified visually, without contrast enhancement
      (sensitivity; 88%, specificity; 100%, accuracy; 91%). Occluded grafts were not
      imaged on CT, either with or without contrast enhancement. We concluded that the
      TDCs of grafts obtained by CT are of no value for predicting the graft flow, and
      that plain CT without contrast enhancement is sufficiently useful for assessing
      the patency of such grafts.

PMID- 1343629
TI  - [Distribution of myocardial damage in patients with hypertrophic cardiomyopathy:
      evaluation by exercise thallium-201 scintigraphy].
AB  - The characteristic of myocardial damage in hypertrophic cardiomyopathy (HCM) was
      evaluated as to whether the damage is limited to the hypertrophied wall or
      extends throughout the entire wall. The myocardial damage was detected by
      exercise thallium-201 (Tl-201) scintigraphy and was evaluated using
      circumferential profile analysis, calculation of initial uptake and washout rate.
      Eleven patients with asymmetrical hypertrophy (ASH), whose septal and posterior
      wall thickness ratio exceeded 1.3 on left ventriculography and
      biventriculography, and 13 age-matched control subjects without heart disease
      were studied. The mean values of initial uptake in both groups did not differ
      significantly, but the washout rate for the entire heart was significantly
      decreased only in the HCM group (p < 0.05). All of the regional washout rates
      (antero-septal, apical and postero-lateral) were significantly decreased in the
      HCM group (p < 0.05), without any difference between the hypertrophied wall and
      the non-thickened free wall being noted. These results demonstrated that the
      analysis of myocardial damage by exercise Tl-201 scintigraphy using calculation
      of the washout rate is a very sensitive means of detecting myocardial damage in
      HCM, and that such myocardial damage is not restricted to the hypertrophied wall,
      but rather extends to the entire wall, including the free wall which is not
      thickened.

PMID- 1343630
TI  - [Left ventricular blood filling in patients with severe mitral stenosis:
      comparisons before and soon after percutaneous transluminal mitral
      commissurotomy].
AB  - To clarify the effects of mitral obstruction on left ventricular (LV) diastolic
      blood filling, 15 patients with tight mitral stenosis (each mitral valve area was
      less than 1.5 cm2) were studied. Each selected patient underwent successful
      percutaneous transluminal mitral commissurotomy (PTMC), which resulted in a 1.5
      fold increase in each mitral valve area. LV pressure, left atrial (LA) pressure
      and cardiac output were measured before and immediately after PTMC. Left
      ventriculography was performed before and immediately after PTMC. The
      ventriculogram was traced frame by frame for one cardiac cycle. The LV volume
      curve was obtained from the traced image using a computer. The LV end-diastolic
      and end-systolic volumes (EDVI, ESVI), and ejection fraction in the subsequent
      cardiac cycle were calculated. The diastolic filling period was divided into 3
      equal parts: namely, early, mid-, and late diastole. The blood volume entering
      the LV during early, mid-, and late diastole, which indicated the filling
      properties of each part, were calculated. After successful PTMC, both the mitral
      valve area (1.1 +/- 0.3 cm2 to 1.9 +/- 0.6 cm2, p < 0.01) and the cardiac index
      (3.2 +/- 0.8 l/min/m2 to 3.6 +/- 1.1 l/min/m2, p < 0.05) increased with the
      decreases in the mean diastolic pressure gradients between the LA and LV (13.4 +/
      4.5 mmHg to 5.9 +/- 2.6 mmHg, p < 0.01). The blood volume entering the LV during
      early diastole increased significantly without significant change in the blood
      volume entering the LV during mid- and late diastole.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1343631
TI  - [Clinical and hemodynamic sequelae of mitral prostheses evaluated by Doppler
      echocardiography].
AB  - To determine the relative superiority of a prosthesis in the mitral position, in
      vivo hemodynamics were examined by Doppler echocardiography, and the results were
      compared with other types of mechanical mitral valves including 63 Bjork-Shiley
      convexo-concave (BS) values, 30 Duromedics (DM) valves, and 58 Medtronic Hall
      (MH) valves. For this comparison, the following indices were evaluated: peak
      velocity of mitral flow (PV), mitral valve orifice area (MVA), mitral valvular
      regurgitation, New York Heart Association (NYHA) classification, pulmonary
      capillary wedge pressure (PC), cardiac index (CI) and valve-related
      complications. On Doppler echocardiograms, PV ranged from 1.2 to 2.0 m/sec with a
      mean of 1.6 m/sec. There was no evident relationship between the PV and the valve
      size in each type of prosthesis, and no significant difference in the PVs among
      the valves. The mean MVA was 2.6 cm2 (25 mm DM, 25 mm MH), which was regarded
      satisfactory from a clinical standpoint. MVA increased with the increase in the
      valve size in all types of valves, and of all sizes, MVA was larger in the DM and
      MH groups than in the BS group. Similarly, the incidence of valvular
      regurgitation was relatively low in all groups, and the degree of regurgitation
      proved to be grade II or less in all cases. As for the clinical results, clinical
      symptoms (NYHA) and hemodynamic states (PC, CI) improved postoperatively, with
      the differences among the types of prosthetic valves being insignificant. The
      incidences of thromboembolism, valvular thrombosis, valve failure and prosthetic
      endocarditis were relatively low in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343632
TI  - [Surgical decisions for active infective endocarditis in patients with acute
      neurological complications].
AB  - The surgical management of 7 patients with active infective endocarditis and
      recent (within 16 days) neurological injury was presented. All patients had
      preoperative computed tomographic scans which revealed no evidence of
      intracranial hemorrhage and underwent successful corrective cardiac surgery. In
      the early postoperative period, 4 patients died of cerebral hemorrhage,
      subarachnoid hemorrhage, or progression of cerebral edema. Two of the 3 surviving
      patients showed no aggravation of cerebral infarcts postoperatively. In the
      remaining surviving patient, intracerebral mycotic aneurysms were resolved
      spontaneously after postoperative antibiotic therapy, although new cerebral
      hemorrhage, a complication of emboli, occurred after open heart surgery. The
      results of this study indicated that 1) cerebrovascular complications were the
      causes of the 4 deaths in this series, and 2) although heparinization during open
      heart surgery may result in intracerebral hemorrhage from mycotic aneurysm or
      infarction, early surgical intervention after recent cardiogenic embolic strokes
      may save patients with minor cerebral infarcts.

PMID- 1343633
TI  - [Magnetic resonance imaging: evaluation of the Blalock-Taussig shunts and anatomy
      of the pulmonary artery].
AB  - The morphology and circulation of the pulmonary arteries and shunt vessels were
      evaluated by magnetic resonance imaging (MRI) in 8 patients with cyanotic heart
      disease after a Blalock-Taussig shunt operation. Their ages ranged from one month
      to 17 years. MRI permitted assessment of the size and patency of the Blalock
      Taussig shunts, as well as the size and morphology of the pulmonary arteries in
      all patients. Measurements of the vessel diameters on MRI correlated well with
      the angiographic measurements (main pulmonary artery, r = 0.98; right pulmonary
      artery, r = 0.98; left pulmonary artery, r = 0.98; and Blalock-Taussig shunt, r =
      0.97). MRI successfully imaged 3 of 4 shunt obstructions and 3 of 4 pulmonary
      stenoses with high resolution. In assessing peripheral pulmonary stenosis or
      obstruction, MRI was superior to echocardiography, the latter being unable to
      image peripheral pulmonary arteries satisfactorily. We concluded that MRI is an
      excellent noninvasive method for serially evaluating the anatomy and function of
      Blalock-Taussig shunts and pulmonary arteries, which is particularly useful for
      children with cyanotic congenital heart disease.

PMID- 1343634
TI  - [Left ventricular systolic time intervals during paroxysmal supraventricular
      tachycardia: the difference between A-V nodal re-entry and A-V re-entry].
AB  - In this study, the differences in hemodynamic changes during paroxysmal
      supraventricular tachycardia (PSVT) between A-V nodal re-entry and A-V re-entry
      were evaluated. In 8 patients with A-V nodal re-entrant tachycardia and 10 with A
      V re-entrant tachycardia, electrophysiological studies were performed to measure
      systolic time intervals (pre-ejection period: PEP, ejection time: ET, PEP/ET
      ratio: PEP/ET). These measurements were obtained in the control state (atrial
      pacing at 90/min) and during PSVT with simultaneous recordings of
      electrocardiogram and femoral arterial pulse tracing. During PSVT, there was no
      difference in the heart rate between the 2 groups, but ventriculo-atrial
      conduction time was shorter in A-V nodal re-entry than in A-V re-entry. There was
      a marked fall in the ET and an increase in PEP/ET in all the patients when PSVT
      was induced. PEP increased significantly in A-V nodal re-entry, but did not
      change in A-V re-entry. This resulted in a greater increase in the PEP/ET
      suggesting a greater deterioration of the hemodynamic consequences in A-V nodal
      re-entry than in A-V re-ent y. Thus, the hemodynamic changes of PSVT differ
      between these 2 types of re-entrant circuits, which are mainly influenced by the
      ventriculo-atrial conduction time.

PMID- 1343635
TI  - [Development of computer software in ramp slope controller for treadmill
      ergometer].
AB  - We developed computer software to produce a treadmill ramp protocol through which
      oxygen uptake (VO2) is increased in a linear fashion, thus enabling subjects to
      walk until the end of exercise. The developed software simulates the increases in
      speed and grade of the treadmill displayed on a personal computer screen, and
      produces the ramp protocol by arbitrarily determining the variables of the
      following formula: 1) Increments of VO2 = a1t+a2 (ml/min/kg) [t = exercise time
      (min)] 2) Predicted VO2 by speed (S) and grade (G) = a3S2 + a4G2 + a5SG + a6S +
      a7G + a8 (ml/min/kg) [S = speed (km/hr); G = grade (%)] 3) Speed suitable for
      desired exercise time (S or S2) = a9t2 + a10t + a11 (km/hr) 4) Grade suitable for
      desired exercise time (G or G2) = a12t2 + a13t + a14 (%) In this study, the
      increment of VO2 was determined by considering the subject's exercise capacity
      (VO2 = 4t + 7 ml/min/kg), using the Ito's formula (VO2 = 0.067S2 + 0.289SG + 7.73
      ml/min/kg). The formula of grade was determined following the formula arbitrarily
      (G2 = 25t + 5%). The formula of speed for exercise time was calculated
      automatically. The new ramp protocol, which was applied to 10 healthy subjects
      (mean age: 24.8 +/- 4.8 years old), disclosed a similar linear relationship
      between the predicted VO2 and the measured VO2.

PMID- 1343636
TI  - [Mechanisms of vasovagal syncope elucidated by upright-tilt with isoproterenol
      infusion].
AB  - To elucidate the role of increased basal vagal activity in vasovagal syncope, we
      compared patients with bradyarrhythmia due to increased vagal tone and patients
      with vasovagal syncope using an upright-tilt (60 degrees) positioning test with
      isoproterenol infusion. Eight patients with unexplained recurrent syncope after
      clinical and electrophysiological investigations and 5 patients without syncope
      who had bradyarrhythmias due to increased vagal tone were studied. All 8 patients
      with recurrent syncope had some prodrome suggestive of vasovagal syncope. The
      upright-tilting test was considered positive if syncope developed in association
      with hypotension or bradycardia, or both. If 10 min of control tilting was
      negative, the patient was lowered to the supine position. Upright-tilting was
      then repeated during continuous intravenous isoproterenol infusion at successive
      incremental doses of 0.01 to 0.03 microgram/kg/min. During the control upright
      tilting test, none of the patients had positive responses. During the upright
      tilting with isoproterenol infusions, all patients with vasovagal syncope had
      positive responses; whereas, all patients with bradyarrhythmia due to increased
      vagal tone had negative responses. In patients with vasovagal syncope, the heart
      rate (HR) and the mean blood pressure (mBP) were higher at the time of supine
      positioning than at the time of syncope (HR: 109 +/- 16-->88 +/- 16 bpm, p <
      0.05) (mBP: 86 +/- 5-->53 +/- 6 mmHg, p < 0.01). However, in patients with
      bradyarrhythmia there was no significant change in HR and mBP between the supine
      and 10 min of the upright-tilting with isoproterenol infusion.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1343637
TI  - [Hemodynamic effects of alcohol ingestion on anaerobic threshold].
AB  - Hemodynamic influence of alcohol ingestion was evaluated using expiratory gas
      analysis in 10 healthy men whose mean age was 26.1 +/- 2.2 years. Protocol of the
      control study (C) was as follows: Oxygen uptake (VO2) at rest and during warm-up,
      anaerobic threshold (AT) and peak VO2 were measured with ramp protocol using a
      bicycle ergometer. AT was determined by the V-slope method. Protocol of the
      alcohol study (A) was as follows: On a different day, the same parameters as C
      were measured after the ingestion of 0.7 g ethanol per kg body weight. The
      following results were obtained: 1) The serum ethanol concentration was 79.1 +/-
      13.5 mg/dl. 2) VO2 in the resting state was higher in A than in C (4.51 +/- 0.74
      vs 3.61 +/- 0.62 ml/min/kg), (p < 0.05). 3) AT and peak VO2 in C and A were 17.15
      +/- 2.76, 32.09 +/- 6.77 ml/min/kg and 15.43 +/- 2.86, 29.60 +/- 5.35 ml/min/kg,
      respectively. 4) Exercise time to the AT in C and A was 222.90 +/- 37.32 and
      172.0 +/- 33.1 sec, respectively. 5) The heart rate was higher in A than in C. It
      was concluded that peak VO2 and AT decreased by alcohol ingestion.

PMID- 1343638
TI  - [High incidence of left ventricular thrombosis and systemic embolism in patients
      with left ventricular assist system].
AB  - The purpose of this study was to determine the incidence of left ventricular (LV)
      thrombosis and systemic embolism in 14 patients with LV assist systems.
      Echocardiography was used to detect LV wall motion abnormalities, intracavitary
      smoke-like echoes and thrombosis, and the effect of anticoagulant therapy was
      serially examined. During full assist of the circulation, the aortic valve did
      not open in any patient. Smoke-like echoes were observed in 9 patients (64%) and
      thrombi in 8 (57%). The thrombus developed within the first 3 assist days.
      Systemic anticoagulant therapy decreased the thrombus size in only 3 patients,
      but there was a possibility of intracranial or mediastinal bleeding in other 3
      patients. Systemic embolism was noted in 7 of 11 autopsy patients (64%). The
      characteristic finding was that there were multiple embolized organs, such as the
      brain, kidneys, spleen and liver, in all patients. Development of a thrombus is a
      serious complication in all patients with LV assist systems. However, the problem
      does not lie in the assist system but in the left ventricle of the patient's own
      heart. It is also noteworthy that systemic anticoagulation is not effective for
      an LV thrombus. A new method of assisting the failing heart, or a new
      anticoagulant delivery technique for the LV cavity to prevent LV thrombus
      development is needed.

PMID- 1343640
TI  - [Cardiac sarcoidosis with multinucleated giant cells detected in endomyocardial
      biopsy specimens: report of 3 cases].
AB  - This is a report of 3 cases of cardiac sarcoidosis. None of the 3 patients had
      other overt systemic involvement. Multinucleated giant cells and non-caseating
      epithelial cell granulomas with small lymphocytic infiltrations were detected in
      the endomyocardial biopsy specimen. Some focal left ventricular wall motion
      abnormalities were detected by echocardiography and angiography in all 3
      patients. Paroxysmal ventricular tachycardia and multifocal ventricular premature
      complexes were observed by Holter 24-hour electrocardiography in all 3 patients.
      Two of the 3 patients did not receive corticosteroids, but remaining patient is
      on a regimen of corticosteroid.

PMID- 1343639
TI  - [Acute hemodynamic effects of pimobendan and captopril: a comparative study in
      the same patients with chronic heart failure].
AB  - In this study, the acute hemodynamic effects of pimobendan (2.5 mg), a new drug,
      was compared with that of captopril (12.5 mg) in the same 8 patients with chronic
      heart failure (NYHA class II-III); 3 with dilated cardiomyopathy and 5 with
      regurgitant valvular heart disease. The hemodynamics were serially assessed
      before and after drug administration for at most 6 hours. Pimobendan reduced mean
      blood pressure, mean pulmonary artery pressure, pulmonary capillary wedge
      pressure, right atrial pressure, total systemic vascular resistance, and total
      pulmonary vascular resistance but it increased heart rate. By contrast, captopril
      reduced mean blood pressure and double product. No significant changes were noted
      in the cardiac index, stroke volume index, AV-O2 difference or the arterial
      oxygen pressure between the 2 drugs. In conclusion, pimobendan seems to function
      as a strong arterio-veno-dilator rather than as an inotropic agent in patients
      with chronic heart failure.

PMID- 1343641
TI  - The physiological control of respiration.

PMID- 1343643
TI  - Evaluation of some organic compounds on bloodstream forms of Trypanosoma cruzi.
AB  - Accidental transmission of Chagas' disease to man by blood transfusion is a
      serious problem in Latin-America. This paper describes the testing of several
      synthetic, semi-synthetic, and natural compounds for their activity against blood
      trypomastigotes in vitro at 4 degrees C. The compounds embody several types of
      chemical structures: benzoquinone, naphthoquinone, anthracenequinone,
      phenanthrenequinone, imidazole, piperazine, quinoline, xanthene, and simple
      benzenic and naphthalenic derivatives. Some of them are for the first time tested
      against Trypanosoma cruzi. The toxic effect of these compounds on this parasite
      was done by two quite distinct sets of experiments. In one set, the compounds
      were added to infected blood as ethanolic solution. In this situation the most
      active one was a furan-1,2-naphthoquinone, in the same range as gentian violet, a
      new fact to be considered in the assessment of structure-activity relationships
      in this class of compounds. In other set, we tentatively evaluated the biological
      activity of water insoluble compounds by adding them in a pure form without
      solvent into infected blood. In this way some appear to be very active and it was
      postulated that the effectiveness of such compounds must result from interactions
      between them and specific blood components.

PMID- 1343642
TI  - Risk factors for Trypanosoma cruzi infection among blood donors in central
      Brazil.
AB  - Characteristics and possible risk factors associated with Trypanosoma cruzi
      infection among blood donors were assessed within a routine screening programme
      in blood banks in an endemic area of Chagas disease. 6,172 voluntary blood donors
      were interviewed and tested for anti-T. cruzi antibodies by Haemagglutination and
      Complement Fixation tests in six blood banks in Goiania-Central Brazil from
      October 1988 to April 1989. An overall prevalence of 2.3% for T. cruzi infection
      was obtained, being 3.3% for first-time blood donors and 1.9% for regular ones (p
      < 0.01). Considering this seropositivity among regular blood donors, selection of
      candidates relying only on the history of previous donation was found to be
      inadequate. The risk of infection increased inversely with the degrees of
      education and monthly income. There was a 9.2 risk of infection (95% CI 3.8-22.6)
      for those who had lived more than 21 years in an endemic area compared to
      subjects who had never lived in rural settings, after multivariate analysis.
      These informations may help to review the criteria of selection of donors in
      order to improve quality of blood products in endemic areas.

PMID- 1343644
TI  - Cytogenetics as a tool for triatomine species distinction (Hemiptera-Reduviidae).
AB  - Several cytogenetic traits were tested as species diagnostic characters on five
      triatomine species: Rhodnius pictipes, R. nasutus, R. robustus, Triatoma
      matogrossensis and T. pseudomaculata. Four of them are described for the first
      time. The detailed analysis of the meiotic process and the application of C
      banding allowed us to identify seven cytogenetic characters which result useful
      to characterize and differentiate triatomine species.

PMID- 1343645
TI  - Relative susceptibility of different stages of Rhodnius prolixus to the
      entomopathogenic hyphomycete Beauveria bassiana.
AB  - Laboratory bioassays were conducted to determine the relative susceptibility of
      eggs, 1st-, 3rd-, 5th-instar nymphs and adults of Rhodnius prolixus to one
      isolate of the entomopathogenic hyphomycete, Beauveria bassiana. Treatments
      consisted of directly spraying on insects of increasing doses of inoculum (3 x
      10(2) to 3 x 10(5) conidia per cm2). Mortality due to all doses of conidia was
      very high in the five tested stages of the target insect. Experiments on eggs
      demonstrated that the fungal isolate was able to kill eggs before they hatched.
      Both time-mortality and dose-mortality responses showed that the susceptibility
      of R. prolixus varied according to its stage of development and increased with
      age. As a matter of fact, at the dose of 3 x 10(3) conidia per cm2, LD 50 varied
      between 11.2 days in 1st-instar nymphs and 6.4 days in both 5th-instar nymphs and
      adults. Comparison of LD50 permitted to estimate that 1st-instar nymphs were
      about 700-fold less susceptible than the two oldest stages.

PMID- 1343646
TI  - Influence of mating on ovarian follicle development in Triatoma infestans (Klug,
      1834).
AB  - This work examines the influence of mating on ovarian follicle development in
      Triatoma infestans. The observations were carried out on both virgin and mated
      females, which were killed at various times after their emergence. There was no
      difference in the ovarian development of both experimental groups during the
      first gonadotrophic cycle. By the 7th day mated females as well as virgin females
      showed vitellogenic oocytes. The coriogenesis and ovulation process began on the
      13th day after imaginal moulting. However we could observe that egg-laying was
      dependent on mating. Mated females laid eggs whereas virgin females did not lay
      eggs. However ovarian production was significantly greater in the mated females.
      It is suggested that in T. infestans mating stimulates egg-laying but it does no
      influence the oogenesis and ovulation process.

PMID- 1343647
TI  - Ultrastructure of the ovary of Dermatobia hominis (Diptera: Cuterebridae). III.
      Gonial cell degeneration.
AB  - We studied the ultrastructural aspects of pre-pupae and pupae ovaries of
      Dermatobia hominis. Physiological degeneration of gonial cells was observed: (a)
      after the ovarioles differentiation, in the oogonia residing in the apical region
      of the ovary; (b) at the beginning of vitellogenesis, in the cystoblasts close to
      the terminal filament. The significance of gonial cell degeneration was
      correlated with the physiological changes which occur in the ovary during
      development.

PMID- 1343648
TI  - Ecology of phlebotomine sand flies (Diptera: Psychodidae) in a focus of
      Leishmania (Viannia) braziliensis in northeastern Colombia.
AB  - The phlebotomine sand fly fauna of two coffee plantations in a Leishmania-endemic
      area of Norte de Santander, Colombia was studied. Regular insect collections
      using a variety of methods were made for three and a half years. Information was
      obtained on diurnal resting sites, host range and seasonal abundance for 17
      species, of which five (Lutzomyia spinicrassa, Lu. serrana, Lu. shannoni, Lu.
      ovallesi and Lu. gomezi) were far more numerous than the others, anthropophilic
      and present throughout the year. The behaviour of these and the remaining 12
      species is discussed in relation to their potential role in transmission of
      Leishmania (Viannia) braziliensis in the area.

PMID- 1343649
TI  - Dispersal of phlebotomine sand flies (Diptera: Psychodidae) in a Colombian focus
      of Leishmania (Viannia) braziliensis.
AB  - Dispersal of five species of phlebotomine sand flies was studied in a coffee
      plantation near Arboledas, Colombia, by mark-release-recapture studies using
      fluorescent powders. The estimated recapture rate for males of Lutzomyia shannoni
      marked and released during the day was 28.1%, significantly higher than that for
      all other species (p < 0.05). Recapture rate of female Lu. shannoni was 9.5%, and
      no females of the other four species were recovered. This suggests either that
      Lu. shannoni is a more sedentary species than the others, or that the large trees
      on which these insects were captured and recaptured function as foci of lekking
      behaviour in males. The high recapture rates of females of this species may
      indicate that oviposition occurs in close proximity to the bases of these trees.
      Although most marked sand flies were recaptured within 200 m of their release
      point, a single female Lu. gomezi was recovered 960 m away 36 h after release.
      This suggests that the dispersal capacity of Lutzomyia species may be greater
      than has been thought, an important consideration in future control programs
      directed against these insects in Leishmania-endemic areas.

PMID- 1343650
TI  - Onchocerciasis in Ecuador: the situation in 1989.
AB  - Details are given of the prevalence rates of onchocerciasis from the most recent
      surveys (1989) conducted in northern Ecuador. The disease has intensified and
      dispersed considerably due to migration of infected individuals and the presence
      of a highly efficient vector. Comparison of these data with those from two
      previous surveys carried out in 1982/83 and 1986 and correlated with
      entomological findings highlight the danger of the formation of new foci of
      onchocerciasis in areas currently free of the disease. Recommendations are made
      for further entomological studies in areas either recently or likely to be
      affected by the disease where potential vectors are unknown or different to those
      registered in the Santiago focus. Ivermectin treatment with local vector control
      in specific areas is advocated to reduce the disease to a low level of public
      health importance.

PMID- 1343651
TI  - The feasibility of forecasting influenza epidemics in Cuba.
AB  - A large influenza epidemic took place in Havana during the winter of 1988. The
      epidemiologic surveillance unit of the Pedro Kouri Institute of Tropical Medicine
      detected the beginning of the epidemic wave. The Rvachev-Baroyan mathematical
      model of the geographic spread of an epidemic was used to forecast this epidemic
      under routine conditions of the public health system. The expected number of
      individuals who would attend outpatient services, because of influenza-like
      illness, was calculated and communicated to the health authorities within enough
      time to permit the introduction of available control measures. The approximate
      date of the epidemic peak, the daily expected number of individuals attending
      medical services, and the approximate time of the end of the epidemic wave were
      estimated. The prediction error was 12%. The model was sufficiently accurate to
      warrant its use as a practical forecasting tool in the Cuban public health
      system.

PMID- 1343652
TI  - Forecast of acute respiratory infections: expected nonepidemic morbidity in Cuba.
AB  - A forecast of nonepidemic morbidity due to acute respiratory infections were
      carry out by using time series analysis. The data consisted of the weekly reports
      of medical patient consultation from ambulatory facilities from the whole
      country. A version of regression model was fitted to the data. Using this
      approach, we were able to detect the starting data of the epidemic under routine
      surveillance conditions for various age groups. It will be necessary to improve
      the data reporting system in order to introduce these procedures at the local
      health center level, as well as on the provincial level.

PMID- 1343653
TI  - Further observations on Lutzomyia ubiquitalis (Psychodidae: Phlebotominae), the
      sandfly vector of Leishmania (Viannia) lainsoni.

PMID- 1343654
TI  - Utilization of a new culture medium in biochemical tests for the mycobacterial
      classification.

PMID- 1343655
TI  - Detection of toxigenic Vibrio cholerae 01 using polymerase chain reaction.

PMID- 1343656
TI  - Human papillomavirus and anogenital cancers in northern Brazil.

PMID- 1343658
TI  - The possibility of occurrence of Trypanosoma rangeli in the state of Tocantins,
      Brazil.

PMID- 1343657
TI  - A Brazilian hepatitis A virus isolated and adapted in primate and primate cell
      line as a chance for the development of a vaccine.

PMID- 1343659
TI  - Endoparasites of Polygenis tripus (Siphonaptera: Rhopalopsyllidae) of wild
      rodents from Belo Horizonte, Minas Gerais, Brazil.

PMID- 1343660
TI  - Comparison of three catching methods for collecting anopheline mosquitoes.

PMID- 1343661
TI  - Molecular karyotype analysis and mapping of housekeeping genes to chromosomes of
      selected species complexes of Leishmania.
AB  - The molecular karyotypes for 20 reference strains of species complexes of
      Leishmania were determined by contour-clamped homogeneous electric field (CHEF)
      electrophoresis. Determination of number/position of chromosome-sized bands and
      chromosomal DNA locations of housekeeping genes were the two criteria used for
      differentiating and classifying the Leishmania species. We have established two
      gel running conditions for optimal separation of chromosomes, which resolved DNA
      molecules as large as 2,500 kilobase pairs (kb). Chromosomes were polymorphic in
      number (22-30) and size (200-2,500 kb) of bands among members of five complexes
      of Leishmania. Although each stock had a distinct karyotype, in general the
      differences found between strains and/or species within each complex were not
      clear enough for parasite identification. However, each group showed a specific
      number of size-concordant DNA molecules, which allowed distinction among the
      Leishmania complex parasites. Clear differences between the Old and New world
      groups of parasites or among some New World Leishmania species were also apparent
      in relation to the chromosome locations of beta-tubulin genes. Based on these
      results as well as data from other published studies the potential of using DNA
      karyotype for identifying and classifying leishmanial field isolates is
      discussed.

PMID- 1343662
TI  - Disseminated American muco-cutaneous leishmaniasis caused by Leishmania
      braziliensis braziliensis in a patient with AIDS: a case report.
AB  - The authors report a case of culture-proven disseminated American muco-cutaneous
      leishmaniasis caused by Leishmania braziliensis braziliensis in an HIV positive
      patient. Lesions began in the oropharynx and nasal mucosa eventually spreading to
      much of the skin surface. The response to a short course of glucantime therapy
      was good.

PMID- 1343663
TI  - Macrophage activation and histopathological findings in Calomys callosus and
      Swiss mice infected with several strains of Trypanosoma cruzi.
AB  - Peritoneal macrophage activation as measured by H2O2 release and histopathology
      was compared between Swiss mice and Calomys callosus, a wild rodent, reservoir of
      Trypanosoma cruzi, during the course of infection with four strains of this
      parasite. In mice F and Y strain infections result in high parasitemia and
      mortality while with silvatic strains Costalimai and M226 parasitemia is sub
      patent, with very low mortality. H2O2 release peaked at 33.6 and 59 nM/2 x 10(6)
      cells for strains Y and F, respectively, 48 and 50 nM/2 x 10(6) for strains
      Costalimai and M226, at different days after infection. Histopathological
      findings of myositis, myocarditis, necrotizing arteritis and absence of
      macrophage parasitism were found for strains F and Costalimai. Y strain infection
      presented moderate myocarditis and myositis, with parasites multiplying within
      macrophages. In C. callosus all four strains resulted in patent parasitemia which
      was eventually overcome, with scarce mortality. H2O2 release for strains Y and F
      was comparable to that of mice-peaks of 27 and 53 nM/2 x 10(6) cells, with lower
      values for strains Costalimai and M226-16.5 and 4.6 nM/2 x 10(6) cells,
      respectively. Histopathological lesions with Y and F strain injected animals were
      comparable to those of mice at the onset of infections; they subsided completely
      at the later stages with Y strain and partially with F strain infected C.
      callosus. In Costalimai infected C. callosus practically no histopathological
      alterations were observed.

PMID- 1343664
TI  - Quantification of Trypanosoma cruzi in the heart, lymph nodes and liver of
      experimentally infected mice, using limiting dilution analysis.
AB  - Limiting dilution analysis was used to quantify Trypanosoma cruzi in the lymph
      nodes, liver and heart of Swiss and C57Bl/10 mice. The results showed that, in
      Swiss and Bl/10 mice infected with T. cruzi Y strain, the number of parasites/mg
      of tissue increased during the course of the infection in both types of mice,
      although a greater number of parasites were observed in heart tissue from Swiss
      mice than from Bl/10. With regard to liver tissue, it was observed that the
      parasite load in the initial phase of infection was higher than in heart. In
      experiments using T. cruzi Colombian strain, the parasite load in the heart of
      Swiss and Bl/10 mice increased relatively slowly, although high levels of
      parasitization were nonetheless observable by the end of the infection. As for
      the liver and lymph nodes, the concentration of parasites was lower over the
      entire course of infection than in heart. Both strains thus maintained their
      characteristic tissue tropisms. The limiting dilution assay (LDA) proved to be an
      appropriate method for more precise quantification of T. cruzi, comparing
      favorably with other direct microscopic methods that only give approximate
      scores.

PMID- 1343665
TI  - Trypanosoma rangeli (Tejera, 1920): observations upon pleomorphism.
AB  - Meta-trypomastigotes of Trypanosoma rangeli Tejera, 1920, harvested from LIT
      medium, were inoculated i.p. or s.c. into 6, 16, and 26 g NMRI mice, these
      representing increasing degrees of immunological maturity. In all cases, similar
      pleomorphic patterns were observed. Four morphobiometrically differentiable types
      of trypanosome were encountered in an overlapping temporal sequence. These
      observations, taken in comparison with those on pleomorphism in this and other
      species of Trypanosoma by other workers, are consistent with the hypothesis that
      the pleomorphic types represent the natural development of the parasite, rather
      than the result of the immune response of the mammal host. Small, slender
      trypanosomes prevalent at the onset of the parasitemia either reinvade the tissue
      cells for relatively limited subsequent generations of tissue reproduction, or
      else differentiate toward the forms that are only capable of colonizing the
      insect vector.

PMID- 1343666
TI  - Trypanosomatidae codon usage and GC distribution.
AB  - A study of Trypanosomatidae GC distribution and codon usage is presented. The
      codon usage patterns in coincidence with the phylogenetical data are similar in
      Crithidia and Leishmania, whereas they are more divergent in Trypanosoma brucei
      and T. cruzi. The analysis of the GC mutational pressure in these organisms
      reveals that T. brucei, and to a lesser extent T. cruzi, have evolved towards a
      more balanced use of all bases, whereas Leishmania and Crithidia retain features
      of a primeval genetic apparatus. Tables with the approximated GC mutational
      pressure in homologous genes, and codon usage in Trypanosomatidae are presented.

PMID- 1343667
TI  - Experimental heteroxenous cycle of Lagochilascaris minor Leiper, 1909 (Nematoda:
      Ascarididae) in white mice and in cats.
AB  - Reports of natural infections of sylvatic carnivores by adult worms of species
      similar to Lagochilascaris minor in the Neotropical region led to attempts to
      establish experimental cycles in laboratory mice and in cats. Also, larval
      development was seen in the skeletal muscle of an agouti (Dasyprocta leporina)
      infected per os with incubated eggs of the parasite obtained from a human case.
      In cats, adult worms develop and fertile eggs are expelled in the feces; in mice,
      larval stages of the parasite develop, and are encapsulate in the skeletal
      muscle, and in the adipose and subcutaneous connective tissue. From our
      observations, we conclude that the larva infective for the mouse is the early 3rd
      stage, while for the final host the infective form is the later 3rd stage. A
      single moult was seen in the mouse, giving rise to a small population of 4th
      stage larvae, long after the initial infection.

PMID- 1343668
TI  - Pterigodermatites (Paucipectines) spinicaudatis n. sp. (Nematoda: Rictularidae)
      from Dromiciops australis (Marsupialia: Microbiotheriidae) in Bariloche, Rio
      Negro, Argentina. Biogeographical distribution and host-parasite relationships.
AB  - Pterigodermatites (P.) spinicaudatis sp. n. from Dromiciops australis is proposed
      and described. The simple morphology of the ovijector and the presence of a well
      developed spine between the two cuticular projections at the caudal extremity of
      the female distinguish the studied nematode from the remainder species of the
      genus parasitizing South American Edentata, marsupials and cricetid rodents. The
      distribution area of the hosts of the different species of P. (P.) are given. The
      studied genus does not parasitize any Australian marsupials. It was found in the
      endemic South American Microbiotheriidae. This fact suggests from a
      parasitological point of view that D. australis is not related to the Australian
      marsupials but to the South American ones.

PMID- 1343669
TI  - Life history studies of heterophyid trematodes in the Neotropical region:
      Ascocotyle (Leighia) hadra sp. n.
AB  - The life cycle of Ascocotyle (Leighia) hadra n. sp. was experimentally
      reproduced, starting from cercariae from naturally infected Littoridina
      parchappei, collected from Los Ranchos stream, near Mercedes city, Buenos Aires
      Province, Argentina. Metacercariae were found encysted in the liver and mesentery
      of experimentally and naturally infected fishes Cnesterodon decemmaculatus and
      Jenynsia lineata. Adults were obtained experimentally in chicks and mice. The
      natural host is unknown. The new species is compared with Ascocotyle (Leighia)
      mcintoshi Price 1936 as described by Leigh, 1974, differing in behavior and
      morphology of cercarial, metacercarial and adult stages.

PMID- 1343670
TI  - Schistosomiasis mansoni in three localities of western lowland of the state of
      Maranhao before and after mass treatments.
AB  - A cross-sectional study for schistosomiasis was carried out in the localities of
      Alianca, Alegre and Coroata (districts of Cururupu, Sao Bento and Sao Joao
      Batista, respectively) in the lowland of the state of Maranhao, after
      respectively 13, 11 and 4 mass treatments with oxamniquine in the period of ten
      years (1977-1987). The study included clinical and quantitative fecal
      examination, skin test for Schistosoma mansoni infection, evaluation of man-water
      contact of the total population (829 persons) in the three localities and other
      epidemiological investigations such as infection rate and dynamics of the snail
      population. After 13 mass treatments in Alianca, the prevalence of S. mansoni
      infection was reduced from 57.9% to 7.4%. In Coroata with 11 mass treatments the
      prevalence fell from 69.2% to 12.8% and in Alegre, with only 4 mass treatments
      there was practically no reduction in prevalence: 22.9% to 21%. After mass
      treatments the type II hepatointestinal clinical form was 10.8% in Alianca, 17.9%
      in Alegre and 18% in Coroata. The hepatosplenic (type III) form was not seen in
      Alianca and Coroata but unexplanably it was 7.6% in Alegre. There was no
      correlation between the egg load elimination and the clinical forms.

PMID- 1343671
TI  - Dengue 2 virus enhancement in asthmatic and non asthmatic individual.
AB  - During the 1981 dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) Cuban
      epidemic, bronchial asthma (BA) was frequently found as a personal or family
      antecedent in dengue hemorrhagic fever patients. Considering that antibody
      dependent enhancement (ADE) plays an important role in the etiopathogenic
      mechanism of DHF/DSS, we decide to study the Dengue 2 virus (D2V) capability of
      replication in peripheral blood leukocytes (PBL) from asthmatic patients and
      healthy persons. In 90% of asthmatic patients and 53.8% of control group it was
      obtained PBL with a significant D2V enhancing activity (X2 p < 0.01). Power
      enhancement was higher in asthmatic group. This is the first in vitro study
      relating BA and the dengue 2 virus immuno enhancement. The results obtained
      support the role of BA as a risk factor for DHF/DSS as already described on
      epidemiological data.

PMID- 1343673
TI  - Delayed phagocytosis and bacterial killing in Chediak-Higashi syndrome
      neutrophils detected by a fluorochrome assay. Ultrastructural aspects.
AB  - The few studies already published about phagocyte functions in Chediak-Higashi
      syndrome (CHS) has stated that neutrophils present slow rate of bacterial killing
      but normally ingest microorganisms. In the present study, both phagocytosis and
      killing of Staphylococcus aureus were verified to be delayed in neutrophils from
      two patients with CHS when these functions were simultaneously evaluated by a
      fluorochrome phagocytosis assay. Electron microscopic examination showed
      morphologic differences among neutrophils from CHS patients and normal
      neutrophils regarding the cytoplasmic structures and the aspects of the
      phagolysosomes. It was noteworthy the presence of giant phagolysosomes enclosing
      bacteria in active proliferation commonly observed in CHS neutrophils after 45
      min of phagocytosis, which corresponded with the impaired bactericidal activity
      of these leukocytes. The present results suggest that phagocytosis may also be
      defective in CHS, and point out to the sensitivity of the fluorochrome
      phagocytosis assay and its application in clinical laboratories.

PMID- 1343672
TI  - Replication of dengue viruses in mosquito cell cultures--a model from
      ultrastructural observations.
AB  - Mosquito cell cultures infected with human sera from dengue-1 and dengue-2
      outbreaks, started in Rio de Janerio by 1986 and 1990 respectively, were examined
      by electron microscopy at different times post the infection of cell cultures.
      More information was obtained about cell penetration of virus particles in the
      presence or not of antibodies, their pathway inside the cells, replication mode
      and exist. Infectiveness of the virus at those different stages can only be
      attributed to the particles appearing inside the trans-Golgi vesicles; most of
      all newly formed virus particles remain inside the RER-derived cell vesicles or
      inside lysosomes, even during cell lysis. Groups of larger particles, 65-75 nm in
      diameter at dengue-2 infections, persist during cell passage. The large amounts
      of smooth membrane structures, as vesicles or tubules inside the RER, are
      attributed to a cell response to viral infection.

PMID- 1343674
TI  - Use of glass beads and CF 11 cellulose for removal of leukocytes from malaria
      infected human blood in field settings.
AB  - Passage of malaria-infected blood through a two-layered column composed of acid
      washed glass beads and CF 11 cellulose removes white cells from parasitized
      blood. However, because use of glass beads and CF 11 cellulose requires
      filtration of infected blood separately through these two resins and the addition
      of ADP, the procedure is time-consuming and may be inappropriate for use in the
      field, especially when large numbers of blood samples are to be treated. Our
      modification of this process yields parasitized cells free of contaminating
      leukocytes, and because of its operational simplicity, large numbers of blood
      samples can be processed. Our procedure also compares well with those using
      expensive commercial Sepacell resins in its ability to separate leukocytes from
      whole blood. As a test of usefulness in molecular biologic investigations, the
      parasites obtained from the blood of malaria-infected patients using the modified
      procedure yield genomic DNA whose single copy gene, the circumsporozoite gene,
      efficiently amplifies by polymerase chain reaction.

PMID- 1343676
TI  - Simian malaria in Brazil.
AB  - In Brazil simian malaria is widely spread, being frequent in the Amazon region
      (10% of primates infected) and even more in the forested coastal mountains of the
      Southeastern and Southern regions (35% and 18% infected, respectively), but
      absent in the semi-arid Northeast. Only two species of plasmodia have been found:
      the quartan-like Plasmodium brasilianum and the tertian-like P. simium, but the
      possible presence of other species is not excluded. P. brasilianum is found in
      all enzootic foci, but P. simium was detected only on the coast of the
      Southeastern and Southern regions, between paralles 20 degrees S and 30 degrees
      S. Nearly all hosts are monkeys (family Cebidae, 28 species harbouring plasmodia
      out of 46 examined), and very rarely marmosets or tamarins (family
      Callitrichidae, 1 especies out of 16). P. brasilianum was present in all infected
      species, P. simium in only two. The natural vector in the Southeastern and
      Southern regions was found to be Anopheles cruzi, but has not been conclusively
      identified in the Amazon. One natural, accidental human infection due to P.
      simium was observed. There is no evidence of the relation of simian to human
      malaria in the Southeastern and Southern regions, where human malaria was
      eradicated in spite of the high rates of monkeys infected, but in the Amazon
      recent serological studies by other workers, revealing high positivity for P.
      brasilianum/P. malariae antibodies in local indians, would suggest that among
      them malaria might possibly be regarded as a zoonosis.

PMID- 1343675
TI  - Non-phenolic method of DNA purification from bacteria, blood samples and other
      biological sources for restriction enzyme assays and the polymerase chain
      reaction.

PMID- 1343677
TI  - Extrachromosomal nucleic acids in bovine Babesia.
AB  - Two kinds of small extrachromosomal nucleic acid elements were found in the
      bovine babesias, Babesia bovis and B. bigemina. One element with an apparent size
      of 5.5 kilobase pairs (kbp) is a double stranded RNA related to virus like
      particles. Another molecule is a double stranded DNA with a molecular size of
      about 6.2 kbp. Southern blot comparison of restriction DNA fragments of the
      latter molecule, which is present in both B. bovis and B. bigemina is described.

PMID- 1343678
TI  - Epidemiology and control of malaria and other arthropod-borne diseases.
AB  - Malaria and other arthropod born diseases remain a serious public health problem
      affecting the lives and health of certain social groups when the two basic
      strategies to control fail due to: (1) the lack of effective
      chemoprophylaxis/chemotherapy or the rapid development of drug resistance of the
      infectious agents and (2) the ineffectiveness of pesticides or the arthropod
      vectors develop resistance to them. These situations enhances the need for the
      design and implementation of other alternatives for sustainable health
      programmes. The application of the epidemiological methods is essential not only
      for analyzing the relevant data for the understanding of the biological
      characteristics of the infectious agents, their reservoirs and vectors and the
      methods for their control, but also for the assessment of the human behaviour,
      the environmental, social and economic factors involved in disease transmission
      and the capacity of the health systems to implement interventions for both
      changes in human behaviour and environmental management to purpose guaranteed
      prevention and control of malaria and other arthropod born diseases with
      efficiency, efficacy and equity. This paper discuss the evolution of the malaria
      and arthropod diseases programmes in the American Region and the perspectives for
      their integration into health promotion programs and emphasis is made in the need
      to establish solid basis in the decision-making process for the selection of
      intervention strategies to remove the risk factors determining the probability to
      get sick or die from ABDs. The implications of the general planning and the
      polices to be adopted in an area should be analyzed in the light of programme
      feasibility at the local level, in the multisectoral context of specific social
      groups and taking in consideration the principles of stratification and equity.

PMID- 1343679
TI  - Epidemiological risk stratification of malaria in the Americas.
AB  - During the last years, malaria had a significant increase in Latin America,
      emerging again as one critical health problem in the Region of the Americas. More
      than 1.04 million new cases were reported in 1990. This resurgence of malaria
      needed a comprehensive strategy for its prevention and control. National malaria
      control programs recognized the epidemiological stratification of malaria as a
      valuable method to assist them in the recognition of local variations and factors
      that specifically contribute to the level and intensity of transmission in
      critical malarious areas. Also it serves as a useful instrument for the selection
      of needed malaria prevention and control activities. The principal feature of
      this approach is to provide a dynamic and ongoing process for assessing the
      epidemiological importance of different risk factors (socio-economic, ecological,
      organization of health services) in malaria transmission. Health interventions
      are based on this assessment and are aimed directly at the reduction or
      elimination of the identified risk factors operating at the local level.
      Intersectorial co-participation and the integration of malaria programs in local
      health services are also important aspects of this public health approach.

PMID- 1343680
TI  - Household-based malaria control in a highly endemic area of Africa (Tanzania):
      determinants of transmission and disease and indicators for monitoring--Kilombero
      Malaria Project.
AB  - The Kilombero Malaria Project (KMP) attempts to define operationally useful
      indicators of levels of transmission and disease and health system relevant
      monitoring indicators to evaluate the impact of disease control at the community
      or health facility level. The KMP is a longitudinal community based study (N =
      1024) in rural Southern Tanzania, investigating risk factors for malarial
      morbidity and developing household based malaria control strategies. Biweekly
      morbidity and bimonthly serological, parasitological and drug consumption surveys
      are carried out in all study households. Mosquito densities are measured biweekly
      in 50 sentinel houses by timed light traps. Determinants of transmission and
      indicators of exposure were not strongly aggregated within households. Subjective
      morbidity (recalled fever), objective morbidity (elevated body temperature and
      high parasitaemia) and chloroquine consumption were strongly aggregated within a
      few households. Nested analysis of anti-NANP40 antibody suggests that only
      approximately 30% of the titer variance can be explained by household clustering
      and that the largest proportion of antibody titer variability must be explained
      by non-measured behavioral determinants relating to an individual's level of
      exposure within a household. Indicators for evaluation and monitoring and outcome
      measures are described within the context of health service management to
      describe control measure output in terms of community effectiveness.

PMID- 1343681
TI  - Human babesiosis in Europe.
AB  - Human babesiosis in Europe came to medical attention in 1957 and until now 19
      cases have been reported, most of them due to Babesia divergens. The onset of the
      disease is characterized by hemoglobinuria, high fever and renal failure ensue
      rapidly. The patients were generally asplenic and resident in a rural area.
      Intraerythrocytic pleomorphic parasites (1-3 microns) observed in stained thin
      blood smears are essential for Genus diagnosis. Parasitemia varied from 5 to 80%
      of red blood cells. Massive blood exchange transfusion (2-3 blood volumes)
      followed by intravenous clindamycin (3-4 times daily) and oral quinine (600 mg
      base, 3 times daily) were successfully used in the treatment of three recent
      cases. Splenectomised individuals should be aware for prevention.

PMID- 1343682
TI  - The level of infestation with the vector of cattle babesiosis in Argentina.
AB  - Studies were carried out to determine the differential aptitude to sustain the
      only vector of cattle babesiosis in Argentina, the tick Boophilus microplus,
      throughout the infested region of this country. Tick counts on Bos taurus cattle
      were used as the main criterion to classify favourable (F), intermediate (I) and
      unfavourable (U) areas for its development. The geographical limits of each area
      were set up using data of non-parasitic tick stages, temperature, water balance
      and map recognition of flooded and unflooded zones. The F area contained 16.5 x
      10(6) ha with a cattle population of 6 x 10(6); the I and U areas had 25 x 10(6)
      ha with 2.7 x 10(6) cattle and 19 x 10(6) with population of 2.4 x 10(6) cattle,
      respectively. Research on the relationship amongst Babesia-Boophilus-cattle is
      needed in the F area for tick development which coincides with the best region
      for cattle breeding.

PMID- 1343683
TI  - Transmission and diagnosis of equine babesiosis in South Africa.
AB  - The transmission and prevalence of Babesia equi and B. caballi are being studied.
      Rhipicephalus evertsi mimeticus an ixodid tick from Namibia was identified as a
      new vector of B. equi, however, R. turanicus, previously reported to be a vector,
      failed to transmit both B. equi and B. caballi in the laboratory. The accurate
      diagnosis of B. caballi is being investigated because the nature of its low level
      parasitaemia does not allow easy detection in thin blood smears, routinely used
      for diagnosis, by clinicians. Consequently its role as a pathogen remains
      obscure. The importance of identifying infected horses, destined for export to
      Babesia-free countries, is also stressed. Thick and thin blood smears, serology
      (IFAT) and DNA probes are currently employed to study disease prevalence. To date
      293 healthy, adult, thoroughbred horses have been screened by all three methods.
      The percentage positives are as follows: B. equi 4.4%, 70.6%, 13% and B. caballi
      0.7%, 37%, 18.4% respectively. The DNA probes were more sensitive than blood
      smear examination for diagnosing carrier infections but are probably not
      sensitive enough to identify all carrier infections. A poor correlation was found
      between detection of the parasites' DNA and seropositivity. However, polymerase
      chain reaction could be used to amplify parasite DNA in a particular sample and
      this could result in more accurate diagnosis.

PMID- 1343684
TI  - Impact of Babesia bovis and Babesia bigemina on the production of beef cattle in
      Uruguay.
AB  - Uruguay is situated in a marginal area for the development of Boophilus microplus
      (30 degrees 35 degrees South Lat.) with important areas of enzootic instability
      for Babesia bovis and B. bigemina. The livestock products represent 70% of our
      exports, for which reason it is fundamental to evaluate the losses in the
      production that these haemoparasites cause as basic information to take future
      decisions. In the period 1988-1990, several works were carried out by our
      laboratory to know the incidence of babesiosis in the reduction of liveweight
      gains. The results are shown and discussed in the work. Experiment I: the weight
      increase of the control group (x = 0.248 kg/day), was 23% higher than that of the
      infected group with Babesia spp (from Uruguay), but significant statistical
      differences were not found (P < 0.05). These animals were kept in boxes and the
      food was controlled for 76 days. Experiment II: the incidence of Babesia spp
      (same strain) was studied for 140 days on Hereford heifers (n = 14) on natural
      pastures. The control group obtained x = 25.29 kg of liveweight gain and it was
      45% higher than that of the infected group, significant statistical difference
      were found (P < 0.05). Experiments with attenuated strains III: four studies were
      carried out inoculating B. bovis and B. bigemina in bovines about one year old,
      in different growth systems, searching for the limit of application. Significant
      statistical differences between those groups were not found during the experiment
      (about 180 days) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343685
TI  - On the current existence of a coccidial line of development in the malaria
      parasites: a theory.
AB  - Most opinion favors the origin of the malaria parasites from a coccidial
      ancestor. It is assumed that whatever the process through which the coccidia
      differentiated into a Plasmodium this phenomenon very probably occurred millions
      of year ago, and during that differentiation process the original coccidia
      vanished. Therefore it has never been repeated. At the light of some experiments
      the existence, at the present time, of a coccidial cycle of development in the
      malaria parasites, is proposed. The connection routes and mechanisms through
      which the malaria parasite changes to a coccidial life, and the routes in reverse
      are exposed. Transmission of the malaria-coccidial forms is suggested.

PMID- 1343686
TI  - Immunogenicity and antigenicity of the N-term repeat amino acid sequence of the
      Plasmodium falciparum P126 antigen.
AB  - The P126 protein, a parasitophorus vacuole antigen of Plasmodium falciparum has
      been shown to induce protective immunity in Saimiri and Aotus monkeys. In the
      present work we investigated its immunogenicity. Our results suggest that the N
      term of P126 is poorly immunogenic and the antibody response against the P126
      could be under a MHC restricted control in C57BL/6(H-2b) mice, which could be
      problematic in terms of a use of the P126 in a vaccine program. However, we
      observed that a synthetic peptide, copying the 6 octapeptide repeat corresponding
      to the N-term of the P126, induces an antibody response to the native molecule in
      C57BL/6 non-responder mice. Moreover, the vaccine-P126 recombinant induced
      antibodies against the N-term of the molecule in rabbits while the unprocessed
      P126 did not.

PMID- 1343687
TI  - Induction of Plasmodium falciparum transmission-blocking antibodies by
      recombinant Pfs25.

PMID- 1343688
TI  - A recombinant hybrid protein as antigen for an anti-blood stage malaria vaccine:
      a study on the conservation of a protective component.
AB  - Recently we have shown that two hybrid proteins expressed in Escherichia coli
      confer protective immunity to Aotus monkeys against an experimental Plasmodium
      falciparum infection (Knapp et al., 1992). Both hybrid proteins carry a sequence
      containing amino acids 631 to 764 of the serine stretch protein SERP (Knapp et
      al., 1989b). We have studied the diversity of this SERP region in field isolates
      of P. falciparum. Genomic DNA was extracted from the blood of six donors from
      different endemic areas of Brazil and West Africa. The SERP region encoding amino
      acids 630 to 781 was amplified by polymerase chain reaction (PCR) and sequenced.
      Only conserved amino acid substitutions in maximally two positions of the
      analyzed SERP fragment could be detected which supports the suitability of this
      SERP region as a component of an anti-blood stage malaria vaccine.

PMID- 1343689
TI  - Development of an immunoenzymatic assay using a monoclonal antibody against a 50
      kDa catabolite from the P126 Plasmodium falciparum protein to the diagnosis of
      malaria infection.
AB  - The WHO criterion of defering any donation of blood by a confirmed case of
      malaria for three years after cessation of therapy can not be applied in areas
      where malaria is endemic. For this reason we developed an immunoenzymatic assay
      for the detection of plasmodial antigens for blood screening in malarial endemic
      areas. So, we tested sera from 191 individuals. Among patients with active
      disease 100% of the cases of Plasmodium falciparum or mixed infections and 91.7%
      of those with P. vivax were positive for the presence of plasmodial antigens. The
      lower parasitaemia detected was 0.0003% for P. falciparum and 0.001% for P. vivax
      malaria. When the frequency of positive circulating malarial antigens was
      evaluated among asymptomatic and symptomatic individuals with negative TBS,
      positive results were found in respectively 38.7% and 17.7% of the individuals
      studied in the 30 days after confirmed malaria attack. Data provide by these
      assays have shown that ELISA seemed to be more sensitive than parasitological
      examination for malaria diagnosis. This test by virtue of its high sensitivity
      and the facilities in processing a large number of specimens, can prove to be
      useful in endemic areas for the recognition of asymptomatic malaria and screening
      of blood donors.

PMID- 1343690
TI  - Non-immunologic methods of diagnosis of babesiosis.
AB  - The diagnosis of tick-borne diseases such as babesiosis still depends on
      observing the parasite in the infected erythrocyte. Microscopic observation is
      tedious and often problematic in both early and carrier infections. Better
      diagnostic methods are needed to prevent clinical disease, especially when
      susceptible cattle are being moved into disease enzootic areas. This study
      evaluates two techniques for early diagnosis of Babesia bovis infections in
      cattle, DNA probes specific for the organism and fluorescent probes specific for
      nucleic acid. The radioisotopically labeled DNA probes are used in slot blot
      hybridizations with lysed blood samples, not purified DNA. Thusfar, the probe is
      specific for B. bovis and can detect as few as 1000 B. bovis parasites in 10
      microliters of blood. The specificity of the fluorescent probe depends on the
      characteristic morphology of the babesia in whole blood samples, as determined
      microscopically. The fluorescent probe detects as few as 10,000 B. bovis
      parasites in 10 microliters os blood. The application of each method for
      laboratory and field use is discussed.

PMID- 1343691
TI  - New methods for the diagnosis of Babesia bigemina infection.
AB  - Accurate diagnosis of Babesia bigemina infection, an economically important tick
      transmitted protozoan parasite of cattle, is essential in the management of
      disease control and in epidemiological studies. The currently used methods of
      diagnosis are blood smear examination and serological tests which include
      agglutination and immunofluorescence tests. These tests have been used in the
      fild but because they lack sensitivity and specificity, newer and improved
      methods of diagnosis are being developed. The quantitative buffy coat (QBC)
      method, using microhaematocrit tubes and acridine orange staining allows rapid
      and quicker diagnosis of B. bigemina and other blood parasites compared to light
      microscopic examination of stained smears. Parasite specific monoclonal
      antibodies have been used in antigen/antibody capture enzymelinked immunosorbent
      assays with greater sensitivity and specificity than previously described
      serological tests. Similarly, DNA probes, derived from a repetitive sequence of
      the B. bigemina genome, offer a method of detecting very small numbers of
      parasites which are undetectable by conventional microscopy. An extrachromosomal
      DNA element, present in all the tick-borne protozoan parasites so far tested,
      provides an accurate means of differentiating mixed parasite populations in
      infected animals. These improved methods will greatly facilitate epidemiological
      studies.

PMID- 1343692
TI  - Detection of Babesia bigemina infection: use of a DNA probe--a review.
AB  - The development of a repetitive DNA probe for Babesia bigemina was reviewed. The
      original plasmid (p(Bbi)16) contained an insert of B. bigemina DNA of
      approximately 6.3 kb. This probe has been evaluated for specificity and
      analytical sensitivity by dot blot hybridization with isolates from Mexico, the
      Caribbean region and Kenya. A partial restriction map has been constructed and
      insert fragments have been subcloned and utilized as specific DNA probes. A
      comparison of 32P labelled and non-radioactive DNA probes was presented. Non
      radioactive detection systems that have been used include digoxigenin dUTP
      incorporation, and detection by colorimetric substrate methods. Derivatives from
      the original DNA probe have been utilized to detect B. bigemina infection in a)
      experimentally inoculated cattle, b) field exposed cattle, c) infected Boophilus
      microplus ticks, and d) the development of a PCR amplification system.

PMID- 1343693
TI  - Polypeptides reactive with antibodies eluted from the surface of Babesia bovis
      infected erythrocytes.
AB  - A technique was sought that would enable identification of surface-exposed
      parasite antigens on Babesia bovis-infected erythrocytes (BbIE) that are not
      detectable by surface-specific immunoprecipitations. Antibodies which bind to the
      surface of BbIE were recovered from intact cells using a low pH wash procedure.
      The eluted antibodies were then used in conventional immunoprecipitation assays
      to identify parasite-synthesized polypeptides carrying epitopes that are exposed
      on the surface or are cross-reactive with such epitopes. The results of these
      experiments support our previous data, obtained using a surface-specific
      immunoprecipitation technique, in the identification of a repertoire of parasite
      derived antigens on the surface of infected erythrocytes (Allred et al., 1991).
      In addition, two polypeptides of M(r) 68,000 and 185,000 were identified which
      react strongly with the eluted antibodies but which are not detected by surface
      immunoprecipitation. These data illustrate the potential of this approach for
      identification of parasite polypeptides which carry epitopes exposed on, or cross
      reactive with exposed epitopes of the infected erythrocyte surface.

PMID- 1343694
TI  - Evaluation of a colorimetric Babesia bigemina-DNA probe within an epidemiological
      survey.
AB  - An epidemiological survey was conducted in southeast Mexico, in an effort to
      establish the serological reactivity and carrier status to Babesia bigemina of an
      indigenous cattle population. The prevalence was obtained through the Indirect
      Fluorescent Antibody Test (IFAT), using an in vitro culture-derived B. bigemina
      antigen. A specific, digoxigenin-coupled, approximately 6 Kb B. bigemina-DNA
      probe (BBDP), was used to indicate the presence of the parasite. Serum samples
      from 925 animals of all ages, were obtained within the three regions (I, II, III)
      of the state of Yucatan and tested by IFAT. In addition, whole blood samples
      drawn from 136 of the same animals of region II were analyzed using the BBDP.
      Positive IFAT (IFAT+) reactions were observed in 531 sera for a 57% overall
      prevalence. Regional values were: I = 157+ (56%), II = 266+ (68%) and III 108+
      (42%). Only 32 (23%) of the blood samples tested with BBDP showed distinctive
      hybridization signal, in contrast with 100 (73%) IFAT+ animals. The response
      distribution for IFAT vs. BBDP was: +/+ 23, +/- 77, -/+ 9 and -/- 27
      respectively. It was found that the analytical sensitivity of BBDP appears to be
      low for its utilization in widespread epidemiological surveys. It was considered,
      however, that the colorimetric probe might be useful to safely detect
      transmission prone carriers, since it is able to detect parasitemias as low as
      0.001%.

PMID- 1343695
TI  - Antibodies in falciparum malaria: what matters most, quantity or quality?
AB  - In view of the recent demonstration that antibodies that are protective against
      Plasmodium falciparum malaria may act in collaboration with blood monocytes, we
      have investigated the isotype content of sera from individuals with defined
      clinical states of resistance or susceptibility to malaria. Profound differences
      in the distribution of each Ig subclass and particularly in the ratio of
      cytophilic versus noncytophilic antibodies were found. In protected subjects, two
      cytophilic isotypes, IgG1 and IgG3 were found to predominate. In non-protected
      subjects, i.e. children and primary attack adults, three different situations
      were encountered: a) an imbalance in which IgG2, a non-cytophilic class,
      predominated (mostly seen in primary attacks); b) an imbalance in which mostly
      IgM antibodies predominated (a frequent event in children) or c) less frequently,
      an overall low level of antimalarial antibodies. Of 33 non immune subjects
      studied all, except one, had one of the above defects. The function of total Ig
      presenting such an isotype imbalance was studied in vitro in Antibody-Dependent
      Cellular-Inhibition assays. Not only did IgG from protected subjects cooperate
      efficiently with blood monocytes, whilst IgG from non-protected groups did not,
      but moreover the latter inhibit the in vitro effect of the former: in competition
      assays whole IgG from primary attack cases with increased IgG2 content, competed
      with IgG from immune adults, thus suggesting that non-protected subjects had
      antibodies to epitopes critical for protection, but that these antibodies are non
      functional.

PMID- 1343696
TI  - A rapid, reliable method of evaluating growth and viability of intraerythrocytic
      protozoan hemoparasites using fluorescence flow cytometry.
AB  - Fluorescence flow cytometry was employed to assess the potential of a vital dye,
      hydroethidine, for use in the detection and monitoring of the viability of
      hemoparasites in infected erythrocytes, using Babesia bovis as a model parasite.
      The studies demonstrated that hydroethidine is taken up by B. bovis and
      metabolically converted to the DNA binding fluorochrome, ethidium. Following
      uptake of the dye, erythrocytes containing viable parasites were readily
      distinguished and quantitated. Timed studies with the parasiticidal drug,
      Ganaseg, showed that it is possible to use the fluorochrome assay to monitor the
      effects of the drug on the rate of replication and viability of B. bovis in
      culture. The assay provides a rapid method for evaluation of the in vitro effect
      of drugs on hemoparasites and for analysis of the effect of various components of
      the immune response, such as lymphokines, monocyte products, antibodies, and
      effector cells (T, NK, LAK, ADCC) on the growth and viability of
      intraerythrocytic parasites.

PMID- 1343698
TI  - In vitro mutagenesis defines drug targets in aldolase of Plasmodium falciparum.

PMID- 1343697
TI  - Basic biochemical investigations as rationale for the design of original
      antimalarial drugs. An example of phospholipid metabolism.
AB  - The future of antimalarial chemotherapy is particularly alarming in view of the
      spread of parasite cross-resistances to drugs that are not even structurally
      related. Only the availability of new pharmacological models will make it
      possible to select molecules with novel mechanisms of action, thus delaying
      resistance and allowing the development of new chemotherapeutic strategies. We
      reached this objective in mice. Our approach is hunged on fundamental and applied
      research begun in 1980 to investigate the phospholipid (PL) metabolism of
      intraerythrocytic Plasmodium. This metabolism is abundant, specific and
      indispensable for the production of Plasmodium membranes. Any drug able to
      interfere with this Plasmodium membranes. Any drug able to interfere with this
      metabolism blocks parasitic development. The most effective interference yet
      found involves blockage of the choline transporter, which supplies Plasmodium
      with choline for the synthesis of phosphatidylcholine, its major PL, this is a
      limiting step in the pathway. The drug sensitivity threshold is much lower for
      the parasite, which is more dependent on this metabolism than host cells. The
      compounds show in vitro activity against P. falciparum at 1 to 10 nM. They show a
      very low toxicity against a lymphoblastoid cell line, demonstrating a total
      absence of correlation between growth inhibition of parasites and lymphoblastoid
      cells. They show antimalarial activity in vivo, in the P. berghei or P.
      chabaudi/mouse system, at doses 20- to 100-fold lower than their acute toxicity
      limit. The bioavailability of a radiolabeled form of the product seemed to be
      advantageous (slow blood clearance and no significant concentration in tissues).
      Lastly, the compounds are inexpensive to produce. They are stable and water
      soluble.

PMID- 1343699
TI  - The treatment of falciparum malaria in children with halofantrine suspension.
AB  - Malaria treatment of children is particularly difficult because of the absence of
      palatable suspensions for young children. Halofantrine hydrochloride is available
      as a suspension which is both palatable and simple to administer, and has been
      studied in a number of trials in the past 5 years. Children (331) ranging from 4
      months to 17 years of age (mean 4.7 years) were treated with the 5% suspension
      using various dose regimens and 364 children ranging from 4 months to 14 years of
      age (mean 5.7 years) were treated with the 2% suspension 6 hourly for 3 doses.
      Using the 3-dose regimen there were only 2/462 (0.4%) who failed to clear the
      initial parasitaemia. Recrudescence occurred in 28/367 (7.6%) children with
      evaluable follow up data. The mean parasite clearance time in this group was 57.1
      h (n = 417) and the mean fever clearance time was 50.9 h (n = 325). Symptoms
      related to malaria cleared rapidly following treatment generally by 24-48 h post
      treatment. Side effects possibly related to treatment were uncommon but were
      similar to those reported in adults. The frequency of diarrhoea and abdominal
      pain was lower than that seen in adults and was also less frequent following
      multiple doses and the use of the more dilute suspension. Since there was
      evidence that the majority of recrudescences were seen in younger children or
      those living in areas with low or seasonal transmission it is recommended that a
      further course of treatment 7 days later is given to these patients to prevent
      recrudescence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343700
TI  - Prevalence and control of babesiosis in the Americas.
AB  - This review presents up-to-date information on the distribution and control
      measures of babesiosis in Latin America. Bovine babesiosis caused by Babesia
      bovis and B. bigemia will be emphasized. The disease is endemic in most countries
      and poses a serious economic burden on livestock production in the region (U.S.
      $1365 million/year, FAO, 1989). Of the estimated 250 million cattle in Central
      and South America, approximately 175 million (70%) are in tick-infested regions.
      Humid, tropical and subtropical areas favor development of the main vector, the
      one-host tick Boophilus microplus. In many regions bovine babesiosis is
      enzootically stable as a consequence of a balanced host-parasite relationship.
      However, Latin America offers a wide range of epidemiologic conditions that are
      influenced by variations from tropical to cool climates and by susceptible
      purebred cattle that are regularly imported to upgrade local stocks. The control
      measures employed in most countries for babesiosis essentially rely on
      chemotherapy, use of acaricides for B. microplus, and to a lesser degree, on
      immunization methods. In general, these measures are expensive, time consuming,
      and in many cases, provide limited success. Finally, the zoonotic potential of
      babesiosis will be addressed, with special emphasis on the situation in the
      United States. Even though bovine babesiosis has long been eradicated from the
      U.S.A., human babesiosis is endemic in the northeastern region of the country.

PMID- 1343701
TI  - Mefloquine resistant malaria in Cameroon and correlation with resistance to
      quinine.
AB  - Based on the results of in vitro sensitivity of Plasmodium falciparum to
      chloroquine, quinine and mefloquine, and evaluation of drug consumption conducted
      in 1987-1988 in four areas in the north and south-west of Cameroon, two opposite
      situations were encountered in this country. In northern Cameroon where
      mefloquine resistance is prevalent a close correlation was found between the
      responses of P. falciparum to mefloquine and to quinine, but not between
      mefloquine and chloroquine. In the south, where chloroquine resistance is highly
      prevalent, no correlation was found neither between mefloquine and chloroquine
      nor mefloquine and quinine, but the responses to quinine and chloroquine appear
      partly correlated. These results lead to formulate the hypothesis of a "southern"
      type of P. falciparum submitted to a high chloroquine drug pressure inducing a
      secondary cross resistance, whilst a "northern" type submitted to a relatively
      high and abortive quinine drug pressure inducing a primary quinine resistance and
      a secondary cross resistance with mefloquine.

PMID- 1343702
TI  - Rational approach of malaria prophylaxis for travellers.

PMID- 1343703
TI  - Babesia divergens vaccine.
AB  - A vaccine strategy against Babesia divergens bovine babesiosis was successfully
      developed after perfecting of an efficient in vitro culture. Crude supernatants
      and purified fractions were able to induce a vaccine protection in gerbils
      against B. divergens infection. More, supernatants induced an effective vaccine
      protection in cattle. The role of B. divergens exoantigens of 17, 37, 46, 70 and
      90 kDa in the development of the immune response was clearly demonstrated in
      gerbils, cattle, and man.

PMID- 1343704
TI  - Field evaluation of an exoantigen-containing Babesia vaccine in Venezuela.
AB  - Bovine babesiosis is endemic in Venezuela, causing significant losses in highly
      susceptible imported cattle. Current immunoprophylactic methods include the less
      desirable use of live parasites. Inactivated vaccines derived from exoantigen
      containing supernatant fluids of in vitro Babesia bovis and B. bigemina cultures
      have been developed and constitute a major improvement in vaccine safety,
      stability and ease of handling. Vaccination trials conducted under field
      conditions provide the final evaluation of a culture-derived B. bovis-B. bigemina
      vaccine. During a 5-year period, approximately 8,000 cattle were vaccinated and
      16 clinical trials carried out in 7 states of Venezuela. Clinical, serologic and
      parasitologic data were collected monthly from 10% of the animals over a 2-year
      period. Data were also collected from a similar number of nonvaccinated control
      cattle. Analysis of results from these trials demonstrated a reduction in the
      incidence of clinical disease among vaccinated animals and complete protection
      against mortality caused by babesiosis. Vaccine efficacy was measured calculating
      the incidence rates of disease and mortality among vaccinated and nonvaccinated
      cattle. Use of this inactivated vaccine offers the best combination of safety,
      potency and efficacy for the effective immunoprophylactic control of bovine
      babesiosis.

PMID- 1343705
TI  - Successful vaccination against Boophilus microplus and Babesia bovis using
      recombinant antigens.
AB  - Current methods for the control of the cattle tick Boophilus microplus and the
      agent of bovine babesiosis, Babesia bovis are unsatisfactory. Effective
      immunological control of both parasites would have great advantages. However,
      naturally acquired immunity to the tick is generally unable to prevent serious
      production losses. A vaccine against the tick, based on a novel form of
      immunization, is being developed. A protective antigen has been isolated from the
      tick, characterized and produced as an effective, recombinant protein. A vaccine
      incorporating this antigen is currently undergoing field trials. In the
      Australian situation, improved tick control will probably increase endemic
      instability with respect to B. bovis. Fortunately, a trivalent, recombinant B.
      bovis vaccine has also been developed. This too is now undergoing pre
      registration field trials.

PMID- 1343707
TI  - Optimization and inhibition of the adherent ability of Plasmodium falciparum
      infected erythrocytes.
AB  - The vast majority of the 1-2 million malaria associated deaths that occur each
      year are due to anemia and cerebral malaria (the attachment of erythrocytes
      containing mature forms of Plasmodium falciparum to the endothelial cells that
      line the vascular beds of the brain). A "model system" for the study of cerebral
      malaria employs amelanotic melanoma cells as the "target" cells in an in vitro
      cytoadherence assay. Using this model system we determined that the optimum pH
      for adherence is 6.6 to 6.8, that high concentrations of Ca2+ (50mM) result in
      increased levels of binding, and that the type of buffer used influences
      adherence (Bis Tris > MOPS > HEPES > PIPES). We also observed that the ability of
      infected erythrocytes to cytoadhere varied from (erythrocyte) donor to donor. We
      have produced murine monoclonal antibodies against P. falciparum-infected red
      cells which recognize modified forms of human band 3; these inhibit the adherence
      of infected erythrocytes to melanoma cells in a dose-responsive fashion.
      Antimalarials (chloroquine, quinacrine, mefloquine, artemisinin), on the other
      hand, affected adherence in an indirect fashion i.e. since cytoadherence is due,
      in part, to the presence of knobs on the surface of the infected erythrocyte, and
      knob formation is dependent on intracellular parasite growth, when plasmodial
      development is inhibited so is knob production, and consequently adherence is
      ablated.

PMID- 1343706
TI  - A study on the pathogenesis of human cerebral malaria and cerebral babesiosis.
AB  - Cerebral complications are important, but poorly understood pathological features
      of infections caused by some species of Plasmodium and Babesia. Patients dying
      from P. falciparum were classified as cerebral or non-cerebral cases according to
      the cerebral malaria coma scale. Light microscopy revealed that cerebral
      microvessels of cerebral malaria patients were filled with a mixture of
      parasitized and unparasitized erythrocytes, with 94% of the vessels showing
      parasitized red blood cell (PRBC) sequestration. Some degree of PRBC
      sequestration was also found in non-cerebral malaria patients, but the percentage
      of microvessels with sequestered PRBC was only 13%. Electron microscopy
      demonstrated knobs on the membrane of PRBC that formed focal junctions with the
      capillary endothelium. A number of host cell molecules such as CD36,
      thrombospondin (TSP) and intercellular adhesion molecule I (ICAM-1) may function
      as endothelial cell surface receptors for P. falciparum-infected erythrocytes.
      Affinity labeling of CD36 and TSP to the PRBC surface showed these molecules
      specifically bind to the knobs. Babesia bovis infected erythrocytes produce
      projections of the erythrocyte membrane that are similar to knobs. When brain
      tissue from B. bovis-infected cattle was examined, cerebral capillaries were
      packed with PRBC. Infected erythrocytes formed focal attachments with cerebral
      endothelial cells at the site of these knob-like projections. These findings
      indicate that cerebral pathology caused by B. bovis is similar to human cerebral
      malaria. A search for cytoadherence proteins in the endothelial cells of cattle
      may lead to a better understanding of the pathogenesis of cerebral babesiosis.

PMID- 1343708
TI  - Variation in the cytoadherence characteristics of malaria parasites: is this a
      true virulence factor?
AB  - The sequestration of Plasmodium falciparum-infected erythrocytes to the
      endothelial cells of brain capillaries is believed to represent one of the
      determining factors in the pathogenesis of cerebral malaria. In vitro studies of
      cytoadherence provide an experimental approach to understand the mechanism of
      sequestration and the respective roles played by parasite and host components in
      this interaction. This paper critically reviews current studies on cytoadherence,
      with particular emphasis on the nature of the information provided by such
      studies and their limitations. The paper also describes how cytoadherence studies
      using the patient's own monocytes can provide original information on the level
      of receptor up-regulation in the course of malarial infection.

PMID- 1343710
TI  - Reorganization of the Brazilian Amazon region and malaria control.

PMID- 1343709
TI  - Cytokines and dysregulation of the immune response in human malaria.
AB  - The dysregulation of the immune response by malaria parasite has been considered
      as a possible constraint to the effectiveness of malaria vaccination. In spite of
      the important role interleukin-1 (IL-1) plays on the immunoregulation, and its
      ability to mimic various features of clinical malaria, reports on IL-1 in malaria
      are lacking. We found that only 2 out of 35 subjects with acute malaria showed
      increased levels of serum IL-1 alpha by enzyme immunoassay. To assess whether IL
      1 could interfere with T-lymphocyte responses, blood mononuclear cells from
      patients infected with Plasmodium falciparum, P. vivax, or healthy subjects were
      cultured with phytohemagglutinin, and lymphocyte proliferation measured 72 h
      later by 3H-thymidine incorporation. Our data showed that T-lymphocyte responses
      are depressed both in P. falciparum (10,500 +/- 2,900) and P. vivax malaria
      (13,000 +/- 3,300), as compared to that of healthy individuals (27,000 +/-
      3,000). Addition of IL-1 partially reversed depression of malaria lymphocytes,
      but had no effect on normal cells. On the other hand, T-lymphocytes from malaria
      infected-subjects presented a minimal decrease in proliferation, when cultured in
      the presence of exogenous PGE2. These data indicate the occurrence of two defects
      of immunoregulation in malaria: a deficiency of IL-1 production by
      monocytes/macrophages, and an increased resistance of lymphocytes to the
      antiproliferative effect of PGE2.

PMID- 1343711
TI  - Epidemiological distribution of Plasmodium falciparum drug resistance in Brazil
      and its relevance to the treatment and control of malaria.
AB  - With the use of a simple formulary, filled by health agents was established a
      monitoring programme for responses of P. falciparum to the antimalarial drugs.
      This monitoring programme is emphasized for the knowledge of the epidemiology of
      the drug resistance and the control of malaria falciparum in Amazon Basin where
      occurs more than 95% of Brazilian malaria cases every year. It was demonstrated
      that still now 4-aminoquinolines have a great importance for the mortality
      control in areas where just SUCAM (National Health Foundation--Health Ministry)
      agents are present without any medical assistance. The results obtained permitted
      the simplification of malaria treatment in Brazil. Important conclusions were
      established in the field of malaria drug resistance.

PMID- 1343713
TI  - Perspective for the production of antimalarial drugs in Brazil.
AB  - There appears to be no chemical manufacture of antimalarial drugs in Brazil.
      Technology at the laboratory process level has been developed for chloroquine,
      mefloquine, pyrimethamine and cycloguanil, but not perfected nor scaled-up,
      largely for economic reasons and market uncertainty. Development of primaquine
      has been contracted but it will run into the same difficulty. Manufacturing
      capacity for sulfadoxine was registered in the SDI by Roche. A project to produce
      artemisinine and its derivatives is under way at UNICAMP-CPQBA but is hampered by
      low content in the plant. Proguanil could be produced easily, but apparently no
      attempt has been made to do so. Quinine is imported on a large scale mostly for
      soft-drink production. Since malarial treatment falls largely within the
      responsibility of the Government health authorities, manufacture of drugs in
      Brazil will depend on an assured medium-term purchase order made to a potential
      local manufacturer, since competition in the world market is scarcely viable at
      the present moment.

PMID- 1343712
TI  - Malaria control--multisectorial approach.

PMID- 1343714
TI  - Efficacy of insecticide impregnated bed-nets to control malaria in a rural
      forested area in southern Cameroon.
AB  - Due to current spreading of chemoresistant strains of Plasmodium falciparum
      malaria control must incorporate vector control programmes. Due to well known
      constraints house sprayings cannot be performed as before. Personal protection
      can be developed and a large scale use of insecticide treated bed-nets appeared
      to be very useful to reduce man-vector contact in Asia, South America and West
      and East Africa. No trial has been done in forest Central Africa where
      transmission is permanent. We performed such a trial in the southern part of
      Cameroon (using deltamethrin, at 25 mg/m2) and obtained similar data to those
      observed in The Gambia, Burkina Faso and Tanzania with a noteworthy reduction of
      both transmission and high parasitaemia of P. falciparum (respectively 78% and
      75%) meaning a drop of malaria morbidity.

PMID- 1343715
TI  - Various pyrethroids on bednets and curtains.
AB  - Verandah trap huts in a Tanzanian village were used to assess the effectiveness
      of impregnated bednets and curtains in preventing hut entry and feeding by, and
      in killing of, Anopheles gambiae and An. funestus. Permethrin, deltamethrin,
      lambdacyhalothrin and pyrethrum were used for impregnation of damaged or
      undamaged bednets, sisal eaves curtains or bed curtains made of polypropylene
      fibre. The performance of the three synthetic pyrethroids did not differ
      statistically significantly, except that on a damaged net permethrin was better
      at preventing feeding. Sisal eaves curtains deterred mosquitoes from hut entry
      but did not kill those that had entered. In assessing damaged nets and curtains
      it must be recognised that anything less than the best vector control may have no
      appreciable impact on holoendemic malaria.

PMID- 1343716
TI  - A malaria merozoite surface protein (MSP1)-structure, processing and function.
AB  - Merozoite surface protein-1 (MSP-1, also referred to as P195, PMMSA or MSA 1) is
      one of the most studied of all malaria proteins. The protein is found in all
      malaria species investigated and structural studies on the gene indicate that
      parts of the molecule are well-conserved. Studies on Plasmodium falciparum have
      shown that the protein is in a processed form on the merozoite surface, a result
      of proteolytic cleavage of the large precursor molecule. Recent studies have
      identified some of these cleavage sites. During invasion of the new red cell most
      of the MSP1 molecule is shed from the parasite surface except for a small C
      terminal fragment which can be detected in ring stages. Analysis of the structure
      of this fragment suggests that it contains two growth factor-like domains that
      may have a functional role.

PMID- 1343717
TI  - Ecology of malaria vectors in the Americas and future direction.
AB  - The resurgence of malaria in the Americas has renewed interest in Anopheles
      biology. Anopheles darlingi, An. albimanus, An. nuneztovai and An. aquasalis are
      reconfirmed as major malaria vectors and other species are playing important
      roles in regional malaria transmission. Adult biting activity and larval ecology
      are discussed in detail. Seasonal abundance and daily biting activity of
      Anophelines vary considerably among species and geographically for the same
      species. Anopheles albimanus has the least amount of variation in biting activity
      over its range and An. darlingi has the greatest. All species studied are more
      exophilic and exophagic than endophilic and endophagic. Anopheles darlingi is
      more anthropophilic, endophilic and endophagic than other Anophelines. Larval
      studies remain more descriptive than comprehensive. Research on Anophelines is
      becoming more integrated and biologists are using new biochemical techniques and
      ecological principles to answer critical questions. This "pluralization" will
      help us understand species complexes, population dynamics and malaria
      transmission. Integrated control programs will require more regional, in-depth
      ecological studies.

PMID- 1343718
TI  - Transmission factors in malaria epidemiology and control in Africa.
AB  - Genetic and environmental components of factors contributing in malaria
      transmission are reviewed. Particular attention is given to density dependent
      regulation of vector populations in relation to the survival rate of anophelines.
      The expectation of vector control activities are different according to the
      epidemiological characteristics of malaria, mainly its stability. In areas with
      perennial and high transmission (stable malaria) vector control could reduce
      malaria related morbidity and mortality, without any effect on the endemicity.
      However this need further investigations. In areas where the transmission period
      is very short (unstable malaria), vector control will have an important impact on
      the disease and on the endemicity. Control projects using indoor spraying with
      insecticide and impregnated bed nets are discussed.

PMID- 1343719
TI  - Vector incrimination and effects of antimalarial drugs on malaria transmission
      and control in the Amazon basin of Brazil.
AB  - World ecosystems differ significantly and a multidisciplinary malaria control
      approach must be adjusted to meet these requirements. These include a
      comprehensive understanding of the malaria vectors, their behavior, seasonal
      distribution and abundance, susceptibility to insecticides (physiological and
      behavioral), methods to reduce the numbers of human gametocyte carriers through
      effective health care systems and antimalarial drug treatment, urban malaria
      transmission versus rural or forest malaria transmission, and the impact of
      vaccine development. Many malaria vectors are members of species complexes and
      individual relationships to malaria transmission, seasonal distribution, biting
      behavior, etc. is poorly understood. Additionally, malaria patients are not
      examined for circulating gametocytes and both falciparum and vivax malaria
      patients may be highly infective to mosquitoes after treatment with currently
      used antimalarial drugs. Studies on the physiological and behavioral effects of
      DDT and other insecticides are inconclusive and need to be evaluated.

PMID- 1343720
TI  - Mechanisms of protective immunity against asexual blood stages of Plasmodium
      falciparum in the experimental host Saimiri.
AB  - In the Saimiri monkey, an experimental host for human malaria, acquired
      protection against Plasmodium falciparum blood stages depends on the IgG antibody
      populations developed. In vivo protective anti-falciparum activity of IgG
      antibodies is correlated with the in vitro opsonizing activity promoting
      phagocytosis of parasitized red blood cells. In contrast, non protective
      antibodies inhibit this mechanism by competing at the target level. A similar
      phenomenon can be observed in human infection. Anti-cytoadherent and anti-rosette
      antibodies developed by Saimiri and humans prevent the development of
      physiopathological events like cerebral malaria which can also occur in this
      experimental host. Furthermore, transfer to protective human anti-falciparum IgG
      antibodies into infected Saimiri monkeys exerts an anti parasite activity as
      efficient as that observed when it is transferred into acute falciparum malaria
      patients, making the Saimiri an even more attractive host. Studies on the role of
      immunocompetent cells in the protective immune response are still in their
      infancy, however the existence of a restricted polymorphism of MHC II class
      molecules in the Saimiri confers additional theoretical and practical importance
      to this model.

PMID- 1343721
TI  - Protection of Aotus monkeys after immunization with recombinant antigens of
      Plasmodium falciparum.
AB  - The genus Aotus spp. (owl monkey) is one of the WHO recommended experimental
      models for Plasmodium falciparum blood stage infection, especially relevant for
      vaccination studies with asexual blood stage antigens of this parasite. For
      several immunization trials with purified recombinant merozoite/schizont
      antigens, the susceptible Aotus karyotypes II, III, IV and VI were immunized with
      Escherichia coli derived fusion proteins containing partial sequences of the
      proteins MSAI (merozoite surface antigen I), SERP (serine-stretch protein) and
      HRPII (histidine alanine rich protein II) as well as with a group of recombinant
      antigens obtained by an antiserum raised against a protective 41 kD protein band.
      The subcutaneous application (3x) of the antigen preparations was carried out in
      intact animals followed by splenectomy prior to challenge, in order to increase
      the susceptibility of the experimental hosts to the parasite. A partial sequence
      of HRPII, the combination of three different fusion proteins of the 41 kD group
      and a mixture of two sequences of SERP in the presence of a modified Al(OH)3
      adjuvant conferred significant protection against a challenge infection with P.
      falciparum blood stages (2-5 x 10(6)) i. RBC). Monkeys immunized with the MS2
      fusion protein carrying the N-terminal part of the 195 kD precursor of the major
      merozoite surface antigens induced only marginal protection showing some
      correlation between antibody titer and degree of parasitaemia. Based on the
      protective capacity of these recombinant antigens we have expressed two hybrid
      proteins (MS2/SERP/HRPII and SERP/MSAI/HRPII) in E. coli containing selected
      partial sequences of SERP, HRPII and MSAI. Antibodies raised against both hybrid
      proteins in rabbits and Aotus monkeys recognize the corresponding schizont
      polypeptides. In two independent immunization trials using 13 animals (age 7
      months to 3 years) we could show that immunization of Aotus monkeys with either
      of the two hybrid proteins administered in an oil-based well tolerated
      formulation protected the animals from a severe experimental P. falciparum
      (strain Palo Alto) infection.

PMID- 1343722
TI  - Efficiency of human Plasmodium falciparum malaria vaccine candidates in Aotus
      lemurinus monkeys.
AB  - The protective efficacy of several recombinant and a synthetic Plasmodium
      falciparum protein was assessed in Aotus monkeys. The rp41 aldolase, the 190L
      fragment of the MSA-1 protein and fusion 190L-CS. T3 protein containing the CS.T3
      helper "universal" epitope were emulsified in Freund's adjuvants and injected 3
      times in groups of 4-5 monkeys each one. The synthetic polymer Spf (66)30 also
      emulsified in Freund's adjuvants was injected 6 times. Control groups for both
      experiments were immunized with saline solution in the same adjuvant following
      the same schedules. Serology for malaria specific antibodies showed
      seroconversion in monkeys immunized with the recombinant proteins but not in
      those immunized with the polymer nor in the controls. Challenge was performed
      with the 10(5) parasites from the P. falciparum FVO isolate. Neither rp41 nor
      Spf(66)30 induced protection, whereas 190L induced significant delay of
      parasitemia. The fusion of the CS.T3 epitope to 190L significantly increased its
      protective capacity.

PMID- 1343723
TI  - Study of humoral immune response in mammals immunized with Plasmodium falciparum
      antigenic preparations.
AB  - Six Plasmodium falciparum protein fractions, isolated under reducing conditions,
      were used to immunize mice, rabbits and the squirrel monkey Saimiri sciureus.
      Five or seven subcutaneous injections of each antigenic preparation, in
      conjunction with Freund's complete or incomplete adjuvants, were administered.
      This led to the development of specific antibodies detected by IFAT, ELISA or
      immunoblotting which inhibited merozoite reinvasion in in vitro P. falciparum
      cultures. This activity seems to be associated with rhoptry proteins contained in
      fractions Pf F2 and Pf F4.

PMID- 1343724
TI  - Impaired renal function in owl monkeys (Aotus nancymai) infected with Plasmodium
      falciparum.
AB  - Impaired renal function was observed in sixteen Aotus nancymai 25 and 3 months
      following infection with the Uganda Palo Alto strain of Plasmodium falciparum.
      Decrease were noted in the clearance of endogenous creatinine, creatinine
      excretion, and urine volume while increases were observed in serum urea nitrogen,
      urine protein, urine potassium, fractional excretion of phosphorus and potassium,
      and activities of urinary enzymes. The results were suggestive of
      glomerulonephropathy and chronic renal disease.

PMID- 1343726
TI  - The role of cytokines in Plasmodium vivax malaria.
AB  - The cytokine tumor necrosis factor and other as yet unidentified factor(s) which
      together mediate the killing of intraerythrocytic malaria parasites are
      transiently elevated in sera during paroxysms in human Plasmodium vivax
      infections in non-immunes. These factors which included TNF and parasite killing
      factor(s) are associated with the clinical disease in malaria to the extent that
      their transient presence in infection sera coincided with paroxysms, the the most
      pronounced clinical disturbances of P. vivax malaria and secondly because their
      levels were markedly lower in paroxysm sera of semi-immune patients who were
      resident of an endemic area. Further, a close parallel was obtained between serum
      TNF levels and changes in body temperature that occur during a P. vivax paroxysm
      in non-immune patients, suggesting a causative role for TNF in the fever in
      malaria. P. vivax rarely if ever cause complicated clinical syndromes.
      Nevertheless serum TNF levels reached in acutely ill P. vivax patients were as
      high as in patients suffering from cerebral complications of P. falciparum
      malaria as reported in studies from the Gambia. Cytokine profiles and other
      changes accompanying clinical disease in P. vivax and P. falciparum malaria are
      compared in this paper with a view to discussing the potential role of cytokines
      in the causation of disease in malaria.

PMID- 1343725
TI  - Plasmodium coatneyi-infected rhesus monkeys: a primate model for human cerebral
      malaria.
AB  - Although several animal models for human cerebral malaria have been proposed in
      the past, none have shown pathological findings that are similar to those seen in
      humans. In order to develop an animal model for human cerebral malaria, we
      studied the pathology of brains of Plasmodium coatneyi (primate malaria parasite)
      infected rhesus monkeys. Our study demonstrated parasitized erythrocyte (PRBC)
      sequestration and cytoadherence of knobs on PRBC to endothelial cells in cerebral
      microvessels of these monkeys. This is similar to the findings seen in human
      cerebral malaria. Cerebral microvessels with sequestered PRBC were shown by
      immunohistochemistry to possess CD36, TSP and ICAM-1. These proteins were not
      evident in cerebral microvessels of uninfected control monkeys. Our study
      indicates, for the first time, that rhesus monkeys infected with P. coatneyi can
      be used as a primate model to study human cerebral malaria.

PMID- 1343727
TI  - Molecular approaches to malaria and babesiosis diagnosis.
AB  - The development of additional methods for detecting and identifying Babesia and
      Plasmodium infections may be useful in disease monitoring, management and control
      efforts. The preliminary evaluate synthetic peptide-based serodiagnosis, a
      hydrophilic sequence (DDESEFDKEK) was selected from the published BabR gene of B.
      bovis. Immunization of rabbits and cattle with the hemocyanin-conjugated peptide
      elicited antibody responses that specifically detected both P. falciparum and B.
      bovis antigens by immunofluorescence and Western blots. Using a dot-ELISA with
      this peptide, antisera from immunized and naturally-infected cattle, and
      immunized rodents, were specifically detected. Reactivity was weak and correlated
      with peptide immunization or infection. DNA-based detection using repetitive DNA
      was species-specific in dot-blot formats for B. bovis DNA, and in both dot-blot
      and in situ formats for P. falciparum; a streamlined enzyme-linked synthetic DNA
      assay for P. falciparum detected 30 parasites/mm3 from patient blood using either
      colorimetric (2-15 h color development) or chemiluminescent detection (0.5-6-min
      exposures). Serodiagnostic and DNA hybridization methods may be complementary in
      the respective detection of both chronic and acute infections. However, recent
      improvements in the polymerase chain reaction (PCR) make feasible a more
      sensitive and uniform approach to the diagnosis of these and other infectious
      disease complexes, with appropriate primers and processing methods. An analysis
      of ribosomal DNA genes of Plasmodium and Toxoplasma identified Apicomplexa
      conserved sequence regions. Specific and distinctive PCR profiles were obtained
      for primers spanning the internal transcribed spacer locus for each of several
      Plasmodium and Babesia species.

PMID- 1343728
TI  - New approaches in in vitro cultures of Plasmodium falciparum and Babesia
      divergens by using serum-free medium based on human high density lipoproteins.

PMID- 1343729
TI  - Human IgG responses against the N-terminal region of the Merozoite Surface
      Protein 1 of Plasmodium vivax.
AB  - The complete primary structure of the gene encoding the Merozoite Surface Protein
      1 of Plasmodium vivax (PvMSP-1) revealed the existence of interspecies conserved
      regions among the analogous proteins of other Plasmodia species. Here, three DNA
      recombinant clones expressing 50, 200 and 500 amino acids from the N-terminal
      region of the PvMSP-1 protein were used on ELISA and protein immunoblotting
      assays to look at the IgG antibody responses of malaria patients from the
      Brazilian amazon region of Rondonia. The results showed the existence of P. vivax
      and P. falciparum IgG antibodies directed against PvMSP-1 antigenic determinants
      expressed in the clones containing the first 200 and the following 500 amino
      acids of the molecule, but not within the one expressing the most N-terminal 50
      amino acids. Interestingly, there was no correlation between the levels of these
      IgG antibodies and the previous number of malaria infections.

PMID- 1343730
TI  - A chromosome 9 deletion in Plasmodium falciparum results in loss of
      cytoadherence.
AB  - Many lines of Plasmodium falciparum undergo a deletion of the right end of
      chromosome 9 during in vitro culture accompanied by loss of cytoadherence and
      gametocytogenesis. Selection of cytoadherent cells from a mixed population co
      selects for those with an undeleted chromosome 9 and the selected cells produce
      gametocytes. The deletion also results in loss of expression of PfEMP1, the
      putative cytoadherence ligand, suggesting that PfEMP1 or a regulatory gene
      controlling PfEMP1 expression and gametocytogenesis may be encoded in this
      region. We have isolated several markers for the deleted region and are currently
      using a YAC-P. falciparum library to investigate this region of the genome in
      detail.

PMID- 1343731
TI  - Characterization of a Plasmodium falciparium mutant that has deleted the majority
      of the gametocyte-specific Pf11-1 locus.
AB  - We identified a gametocyte-specific protein of Plasmodium falciparum called Pf11
      1 and provide experimental evidence that this molecule is involved in the
      emergence of gametes of the infected erythrocyte (gametogenesis). A mutant
      parasite clone, which has deleted over 90% of the Pf11-1 gene locus, was an
      important control to establish the gametocyte-specific expression of the Pf11-1.
      Molecular analysis of the Pf11-1 deletion indicates that it is presumably due to
      a chromosome breakage with subsequent 'healing' by the addition of telomeric
      heptanucleotides. Moreover, similar DNA rearrangements are observed in most of
      the laboratory isolates during asexual propagation in vitro.

PMID- 1343732
TI  - Deletion, insertion and translocation of DNA sequences contribute to chromosome
      size polymorphism in Plasmodium berghei.
AB  - Extensive chromosome size polymorphism arises in Plasmodium berghei during in
      vivo mitotic multiplication. Size differences between homologous chromosomes
      mainly involve rearrangements in the subtelomeric regions while internal
      chromosomal regions are more conserved. Size differences are almost exclusively
      due to differences in the copy number of a 2.3 kb subtelomeric repeat unit. Not
      only deletion of 2.3 kb repeats occurs, but addition of new copies of this repeat
      sometimes results in the formation of enlarged chromosomes. Even chromosomes
      which originally lack 2.3 kb repeats, can acquire these during mitotic
      multiplication. In one karyotype mutant, 2.3 kb repeats were inserted within one
      of the original telomeres of chromosome 4, creating an internal stretch of
      telomeric repeats. Chromosome translocation can contribute to chromosome size
      polymorphism as well. We found a karyotype mutant in which chromosome 7 with a
      size of about 1.4 Mb is translocated to chromosome 13/14 with a size of about 3
      Mb, resulting in a rearranged chromosome, which was shown to contain a junction
      between internal DNA sequences of chromosome 13/14 and subtelomeric 2.3 kb
      repeats of chromosome 7. In this mutant a new chromosome of 1.4 Mb is present
      which consists of part of chromosome 13/14.

PMID- 1343733
TI  - [The Rio Conference or the environmental samba].

PMID- 1343734
TI  - Effects of thyroidectomy on biochemical and ultrastructural aspects of rat slow
      and fast muscles.
AB  - Thyroidectomy provoked the reduction of the oxygen consumption rate in state 3
      respiration in both Extensor Digitorum Longus (EDL, fast twitch) and Soleus (slow
      twitch) muscles of rat, being the last one the most affected. Morphological
      alterations after 8 weeks of thyroidectomy were found in mitochondria. These
      organelles exhibited cristae swelling and formation of autophagic vacuoles in
      subsarcolemmal and intermyofibrillar spaces. Altered mitochondria were also seen
      in the axon terminal and the postjunctional region of motor end-plate.

PMID- 1343735
TI  - [Bacillary necrosis in larvae of the bivalve Euvola ziczac (Linnaeus, 1758)
      caused by a Pseudomonas sp].
AB  - The incidence of bacteria as etiological agents of diseases in larvae of bivalve
      mollusks, is well documented in the literature. In this study, a series of test
      were performed to identify and estimate pathogenic level of marine bacteria
      isolated during an epizootic in a larval culture system of the tropical scallop
      Euvola ziczac. Such bacteria was identified as Pseudomonas sp. belonging to the
      group alcaligenes. The bacterium produced not only lethal effects on the scallop
      larvae through infection (invasive action), but also a possible pathogenic
      activity through endotoxins associated to bacterial cell-wall. In addition, it is
      possible that the isolated bacteria could act as a pathogen with members of the
      genus Vibrio, which was also present during the epizootic outbreak in the culture
      system. Susceptibility of Pseudomonas sp. to commercial antibiotics was
      remarkable.

PMID- 1343736
TI  - Hydrolytic activity of an onchocercoma.
AB  - The onchocercoma or nodule produced by the nematode Onchocerca volvulus
      (Filarioidea) in the skin of patients suffering from onchocerciasis has not been
      examined by histochemical techniques. In this work we have used histochemical
      techniques to evaluate 5 hydrolytic enzymes, namely phosphatases, esterases and
      beta-glucuronidase. The results show increased enzymatic activity at the sites of
      major metabolic activity and within reactive cells including macrophages (mc) and
      giant cells (gc) of the onchocercoma.

PMID- 1343737
TI  - Ultrastructure of an iguana fast twitch denervated muscle.
AB  - This ultrastructural study was undertaken to investigate the morphological
      changes which occur in the fast twitch gastrocnemius muscle of the reptile Iguana
      iguana after nerve section. It was found that initial degenerative alterations
      appeared in muscle fibers two weeks after denervation and progressed along the
      two months of the investigative period. They consisted of disorganization of
      contractile and sarcotubular elements and the appearance of autophagic vacuoles
      with mitochondrial debris. However, even two months after nerve section some
      myofibrils and mitochondria looked normal. Our results suggest that although the
      general course of denervation atrophy in iguana gastrocnemius is similar to that
      in other twitch muscles of vertebrates, the chronology of the process shows that
      iguana fast twitch skeletal muscles exhibit an intermediary position among the
      vertebrates in relation to their velocity of response to denervation.

PMID- 1343738
TI  - [Production and characterization of monoclonal antibodies directed against the
      hepatitis B surface antigen].
AB  - Hepatitis B virus surface antigen (HBsAg) found in a commercial vaccine was use
      as immunogen and antigen for the production and selection of murine monoclonal
      antibodies against this viral antigen. Antibody relative avidity was determined
      based on their capture capacity. Competition studies, and the differential
      recognition pattern of vaccine preparations showed that high avidity IgG1
      antibodies were directed against two distinct antigenic regions. Among them, 6F4
      was most suitable for the detection of HBsAg in a sandwich ELISA system, using an
      IgM antibody, 5E8, as capture. However, the combined use of 6F4 with another
      which does not recognize the same epitope did not improve the sensitivity of the
      assay. On the other hand, the combination of 6F4 with a lower avidity IgG1
      antibody, 6G10, increased the universe of antigenic diversities recognized by
      this system. An enzyme immunoassay for detection of HBsAg is proposed, using 3
      monoclonal antibodies: one IgM as capture and two IgG1 for detection.

PMID- 1343739
TI  - [Biomolecules suppressing myelopoiesis].
AB  - Hematopoietic stem cells are capable of self-replication and differentiation to
      lineage-committed progenitor cells. The progenitors proliferate and differentiate
      to lineage-specific, morphologically recognizable precursors and, finally, to
      terminal circulating blood cells. These homeostatic mechanisms are regulated by a
      complex set of interacting growth stimulatory and inhibitory factors that are
      produced by, or in collaboration with, the tissue's regulatory microenvironment.
      A number of well-characterized cytokines have been implicated in the negative
      regulation of hematopoiesis: ferritin H-subunit (HF), lactoferrin (Lf),
      prostaglandin E (PGE), tumor necrosis factor (TNF), interferon (IFN),
      transforming growth factor-beta (TGF beta), acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) or
      thymosin-beta 4, pyroGlu-Glu-Asp-Cys-Lys (pEEDCK), macrophage inflammatory
      protein-1 alpha (MIP-1 alpha), inhibin, superoxide dismutase (SOD), glutathione
      (GSH) and others not well-known yet. The role of inhibitors in restraining stem
      cells from entering the cell cycle and protecting them from the toxic side
      effects of chemotherapeutic drugs is opening an alternate strategy for the
      treatment of cancer patients.

PMID- 1343740
TI  - Intramuscular capillary abnormalities in a case of myotonic dystrophy (Steinert's
      disease).
AB  - The structural study of a muscle biopsy from a case of myotonic dystrophy showed
      endothelial cell and pericyte alterations, and infiltration of lymphocytes,
      macrophages and mast cells. The histopathological picture was similar to that
      observed in the muscular compromise of some autoimmune diseases. These findings
      are interesting because although the aetiology of myotonic dystrophy is still
      obscure, it has been suggested that in the origin of this disease could be
      involved either primary muscle fibre damage or that myotonic dystrophy is
      neurogenic, propositions apparently not directly connected with a relation cause
      effect to intramuscular capillary abnormalities.

PMID- 1343741
TI  - Trypanosoma cruzi: infectivity and virulence of trypomastigotes incubated with
      leukocytes and serum from patients with Chagas' disease.
AB  - An important issue for the understanding of the host-parasite relationship in
      Chagas' disease is the extent of the action of the immune system on the parasite.
      To advance our understanding of this aspect, we evaluated the effect of
      leukocytes and/or sera from patients with Chagas' disease on trypomastigotes of
      Trypanosoma cruzi. We incubated, in vitro, leukocytes and sera, from patients
      with Chagas' disease without evidence of heart disease (INF), patients with
      Chagasic cardiopathy (CDM) and healthy controls (VOL), with trypomastigotes at 37
      degrees C for three hours. Mice were inoculated with parasites at the end of the
      incubation. We kept a record of the survival time of each animal and every three
      days we evaluated their Parasitemia. INF (36.4%) and CDM (42.9%) prolonged the
      prepatent period, but not Vol. Only CDM (57.1%) extended the survival time. The
      sera from CDM patients that extended the survival of mice prolonged the prepatent
      period. However serum alone did not extend the survival time, providing evidence
      that leukocytes are required to decrease the virulence of the inoculum. The
      capacity of leukocytes and sera, from CDM, to prolong survival time shows that
      the immune system of patients with Chagasic cardiomyopathy can affect the
      parasite more intensely than IFN. On the other hand, the higher frequency of
      positive xenodiagnosis in CDM (11), suggests that, in vivo, occur a down
      regulation of the immune response.

PMID- 1343743
TI  - Vegetable gums modify lectin hemagglutinability.
AB  - Arabic gum enhances lectin hemagglutinability. The more glycosylated the lectin,
      the greater the stimulatory effect of the gum. Evidence presented suggests that
      the interaction between gum and lectin is of a carbohydrate-carbohydrate nature.

PMID- 1343742
TI  - [In vitro stimulation of Leydig cells with human chorionic gonadotropin in adult
      rats of different ages].
AB  - We studied the functional reserve of Leydig cells in adult rats of different ages
      in vitro. Suspensions of Leydig cells after digestion by collagenase were
      stimulated with Human Chorionic Gonadotropin (hCG) during different times (1, 3
      and 5 hours). We observed that response of Leydig cells, expressed by the
      testosterone concentration in the culture medium, showed a similar pattern in all
      studied group, and the highest response was seen at three hours of incubation. On
      the other hand, the testosterone response to hCG varied with age of animal. Thus,
      it was higher in the group of 14 months old (middle aged) than young animals (5
      month old) and decreased in old animals (21 months old). These results suggest
      that a primary testicular lesion occurs with aging.

PMID- 1343744
TI  - [Scientific publication in the Andean subregion].

PMID- 1343746
TI  - Characterization of polycyclic aromatic hydrocarbons degradative soil
      Pseudomonas.
AB  - Nine Pseudomonas strains, able to degrade polycycle aromatic hydrocarbons (PAHs),
      were isolated from enriched cultures with naphthalene, as carbon source, and soil
      samples from a land farming process applied on oil sludge, as inocula.
      Degradative tests showed that all the strains were capable to catabolize
      naphthalene (Nah) and phenanthrene (Phn). U2 strain transferred the selected
      function (Nah) to P. aeruginosa T1 (Hgr Oct+), however some of the
      transconjugants lost the Oct character, suggesting that it is of plasmidic
      nature. T1 derivatives as well the wild strains U28 and U31 transferred Nah
      function to P. putida AC165. All of the examined transconjugants also catabolized
      phenanthrene, suggesting that Nah and Phn functions in U2, U28, and U31 strains
      are linked and probably encoded by transferable plasmids.

PMID- 1343745
TI  - Molecular mimicry between Trypanosoma cruzi and host nervous tissues.
AB  - Increasing evidence suggests that in Chagas' disease chronic-phase pathology is
      autoimmune in nature. There are at least two nonexclusive explanations for the
      generation of autoimmunity in Chagas disease: a) infection with the parasite
      perturbs immunoregulation, leading to loss of tolerance for self-antigens; b)
      immune recognition of T. cruzi antigens is crossreactive with selected mammalian
      antigens, leading to autoimmunity (molecular mimicry). Through this latter
      mechanism, T. cruzi antigens that share epitopes with mammalian nervous tissue
      may drive autoreactive B- or T-cell clones to expand and cause autoimmune lesions
      in chronic chagasic patients. Several different antigens sharing this
      characteristic have been studied, as for example the 160-kDa flagellum-associated
      surface protein (Fl-160), which has a nervous tissue crossreactive epitope
      composed by twelve amino acids. Additionally, it has been demonstrated that a
      trypomastigote stage-specific 85kDa surface glycoprotein (Gp85) has terminal
      galactosyl(alpha 1-3)galactose terminal residues, which are reactive with chronic
      chagasic sera. Common glycolipid antigens have also been reported, as for example
      galactocerebroside, sulfogalactocerebroside and sulfoglucuronylcerebroside, all
      of them specifically present at high concentrations in mammalian nervous system
      and in T. cruzi trypomastigotes. Chronic chagasic patients produce elevated
      levels of antibodies against these three glycolipid antigens. They also do
      against terminal galactosyl(alpha 1-3)galactose residues present on several acid
      and neutral glycolipids common either to nervous system or parasite. These
      antibodies are powerful lytic for circulating T. cruzi trypomastigotes. Another
      common strongly immunogenic residues are galactosyl(alpha 1-2)galactose,
      galactosyl(alpha 1-6)galactose and galactofuranosyl(beta 1-3)mannose residues
      present on several glycoinositolphospholipids (GIPL), against which chronic
      chagasic patients have elevated levels of specific antibodies. In brief, very
      specific host-parasite relationships existing only in Chagas' disease may explain
      the particular peripheral nervous tissue damage seen in acute or chronic stages
      of this disease. This specificity could depend either on invasion of autonomic
      ganglia by T. cruzi trypomastigotes and modification of nervous cell surface
      structures by some of the several mechanisms of acquired molecular mimicry.

PMID- 1343747
TI  - [Characterization of Paracoccidioides brasiliensis antigens. Serological
      immunodiagnosis using western blotting].
AB  - The electrophoretic characterization on SDS-PAGE gels of Paracoccidioides
      brasiliensis antigens, strains 2511 and 6688; and the additional use of
      immunoblotting has permitted in this study to identify the immunogenic, sensitive
      and specific antigen fractions for the diagnosis of Paracoccidioidomycosis. The
      antigenic preparations showed differences depending on the morphologic form of
      the fungus and the method utilized. The procedure revealed heterogeneity in the
      humoral immune response of the patients studied and permitted us to establish
      indices of activity of Paracoccidioidomycosis by the sequential analysis of sera
      obtained during different stages of the disease. The high sensitivity of this
      method makes it useful as an additional technique for the serologic
      immunodiagnosis of Paracoccidioidomycosis.

PMID- 1343748
TI  - [Value of combined electro- and vectorcardiography in the estimation of left
      ventricular mass in the elderly].
AB  - Electro- and vectorcardiographic methods describe left ventricle increases only
      when it has attained a significantly high magnitude, but even in such
      circumstances the exactitude of such methods is substantially lower than that of
      echocardiogram (ECHO). On the other hand, in comparison to other age groups,
      there have been relatively few reports relating electrocardiogram (ECG),
      vectorcardiogram (VCG) and ECHO with left ventricular mass (LVM) in healthy
      elderly subjects where increases of the left ventricle mass, if present, would be
      small or moderate. In this paper LVM as well as LVM index (iLVM) from a group of
      healthy subjects belonging to a physical training program for elderly, was
      studied by means of ECHO and computerized ECG and VCG. From ECG, voltage indexes
      and other LVM associated parameters were extracted; from VCG, planar maximum
      vectors, areas within VCG loops and maximal spatial magnitude of QRS (SM), were
      measured. Results of LVM (221 +/- 37.9, g) were higher than figures reported for
      others groups. Voltage indexes showed normal values, but QRS duration was
      somewhat prolonged. The best simple linear regression, combining variables from
      VCG and ECG was maximum horizontal vector (Vmax-Hor) vs Sokolow-Lyon index (SOK)
      and combining ECHO with ECG or VCG, LVM vs Area inside horizontal loop (AreaHor).
      A model for estimation of LVM from electrical variables was obtained by multiple
      linear regression; combining five variables from ECG and VCG. The best model
      included Sokolow-Lyon index and variables from horizontal and sagittal planes of
      VCG and spatial magnitude of QRS: LVM = 4.8 SOK-186 VmaxHOR-80 VmaxSAG + 126SM +
      340 AreaH + 175.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343749
TI  - [Molecular epidemiology of human rotavirus in Cumana, Venezuela].
AB  - During the period January to December 1987, rotaviruses were obtained from
      infants hospitalized with acute gastroenteritis in Cumana, Venezuela, and were
      compared by analysis of the migration of their double-stranded ribonucleic acid
      (RNA) genome segments in polyacrylamide gel electrophoresis. Rotavirus RNA was
      detected in 87 (17.03%) of 511 faecal samples, and at least 12 different
      electropherotypes were recognized throughout the period of study. Of the
      rotavirus positive samples, 86 (98.85%) had a "long" electrophoretic pattern
      characteristic of human rotavirus subgroup 2. The incidence of rotavirus
      infection was statistically related with the age, sex, and nutritional status of
      the pediatric patients for epidemiological purposes. This statistical relation
      was very significant with the age and the nutritional status of the patients but
      not with their sex.

PMID- 1343751
TI  - Uterine factors in repeated miscarriage.

PMID- 1343750
TI  - Endocrine aspects of recurrent early fetal wastage. The role of luteal phase
      inadequacy.

PMID- 1343752
TI  - Oocyte quality and assisted conception.

PMID- 1343753
TI  - Treatment strategies for severe ovarian hyperstimulation.

PMID- 1343754
TI  - LHRH analogues and PCO disease: validity of the use of enantone depot in the
      treatment of the disease.
AB  - The Authors have been showed the utility of LHRH analogues in the treatment of
      PCO disease, through hormonal dosages and echographic examination made before,
      during and after the therapy both with Enantone depot, CPA and EE2, and with only
      CPA and EE2 of control cases. The association of analogue to traditional therapy
      has determined a more speedy reduction of haematic levels of LH, T free, DHEA-S,
      than the ones we have found in control case, an evident reduction (50%) of
      pilonidal growth and an important improvement of acne and seborrhea.

PMID- 1343755
TI  - Ultrastructural sperm investigations in normospermic subjects with repeated
      failures of oocyte fertilizations.

PMID- 1343756
TI  - [Effect of aging on schizophrenia].
AB  - The problem of the senescence's influence on schizophrenia and the right to
      detach this variable from those who take care of temporal evolution is
      complicated. From a population of 99 schizophrenic patients (DSM III criteria's)
      having most of 60 year old and most of 20 years schizophrenia's disease
      evolution; we have study the whole or partial imputability to the senescence of
      residential statute's modification; frequency, reason, duration of
      hospitalization's change, psychotic's symptom levelling; and therapeutic's
      instability.

PMID- 1343757
TI  - [Contribution of single photon emission computerized tomography (SPECT-HMPAO) to
      the study of schizophrenia].
AB  - The authors studied a group of thirteen schizophrenic patients with functional
      brain imaging, using single-photon-emission-computed tomography (S.P.E.C.T.). The
      radiotracer was the H.M.P.A.O. labelled with 99 m Technetium. All were being
      given neuroleptic drug. Forty-one lesions demonstrated decreased perfusion. These
      functional abnormalities are mainly located in the left hemisphere and this
      asymmetry is more pronounced in positive-symptom schizophrenics. However, at
      rest, these correlations are limited and finally we demonstrated a wide spectrum
      of metabolic dysfunctions in the same subtype of schizophrenia.

PMID- 1343758
TI  - [Measuring quality of life].
AB  - The four broad domains of quality of life are the physical status and functional
      abilities, the psychological status and well-being, the social interactions and
      the economic status and factors. Health profiles attempt to measure all important
      aspects of Quality of Life (QOL). They offer a number of advantages and they also
      have some limitations. A number of QOL indexes have been recently developed to
      measure emotional and social functions, well-being as well as overall health
      status. Some scales used to evaluate QOL are function-specific as social
      interactions scales or daily living scales; others are disease-specific. For the
      severely mentally ill patients the most comprehensive and psychometrically best
      characterized scales have been recently reviewed. The Lehman's Structured Quality
      of Life interview for example based on comprehensive quality of life models,
      includes both subjective and objective QOL indicators and should be extensively
      used in french clinical studies.

PMID- 1343759
TI  - [Mourning, widowhood and psychopathology].

PMID- 1343761
TI  - [Tolerance, the primary condition in psychotherapy of delusions].

PMID- 1343760
TI  - [Recent studies of the genetics of manic-depressive disorder and schizophrenia].

PMID- 1343762
TI  - [Psychiatric selection of European astronauts: the French experience].
AB  - In order to realize the future Hermes and Columbus space-flights, European Space
      Agency decided to build up a european astronaut corps. Space-flights and training
      constraints require a strict initial selection among candidates. This paper
      describes space-flights psychological constraints, the aims of a psychiatric exam
      and its position in astronaut selection procedures as a whole. This paper also
      describes means and results of that selection among the candidates seen in Paris
      (France) in 1991.

PMID- 1343763
TI  - [Athymormia, arithmomania or stercoral compulsion in multiple infarcts of the
      corpus striatum].

PMID- 1343764
TI  - Autoimmune vasculitis in MRL/Mp-lpr/lpr mice: orthochromatic basophils
      participate in the development of delayed-type hypersensitivity angiitis.
AB  - The pathogenesis of autoimmune vasculitis is poorly understood. Understanding the
      immunologic mechanisms governing this disease requires precise identification of
      the cells which comprise the lesion. In this report, we have evaluated tissue
      sections from MRL/lpr mice from 16 to 45 weeks of age, representing all stages of
      clinical vasculitis. We demonstrate that basophil myelocytes participate in the
      evolution of the delayed-type hypersensitivity (DTH) response which initiates and
      perpetuates autoimmune vasculitis in these mice. These findings raise questions
      regarding the immunologic mechanisms by which basophils develop in this lesion
      and the interaction of basophils. VSMCs and lymphocytes in vasculitic
      angiodestruction.

PMID- 1343765
TI  - Inhibition of experimental autoimmune uveoretinitis by oral administration of S
      antigen and synthetic peptides.
AB  - S-Antigen, a photoreceptor cell protein, is highly efficient in inducing
      experimental autoimmune uveoretinitis (EAU), a severe inflammation of the uveal
      tract and retina of the eye. S-Antigen and six synthetic peptides, all of which
      correspond to known T-cell or B-cell recognition sites, were tested for their
      ability to induce oral tolerance to EAU in LEW rats. Feeding three 1-mg doses of
      native S-Antigen or three doses of one synthetic peptide, designated BSA(343-362)
      (200 micrograms per dose), reduced the incidence and severity of EAU induced by
      immunization with 50 micrograms of S-Antigen. Another peptide, BSA(270-289), was
      able to inhibit EAU only when a low dose (10 micrograms) of the uveitogenic S
      Antigen was used to induce EAU. Animals which received 200 micrograms doses of
      four other immunologically active peptides, BSA(31-51), BSA(143-162), BSA(303
      327) and BSA(333-352), were not significantly protected. Furthermore, animals fed
      BSA(343-362) were significantly less susceptible to EAU induced by adoptive
      transfer (tEAU) of the uveitogenic R9 T-cell lines. Con A-activated lymphocytes
      purified from spleens of rats fed peptide BSA(343-362) transferred partial
      resistance to tEAU induced by adoptive transfer of R9 line cells. The resistance
      of orally tolerized rats to induction of EAU by adoptive transfer of an
      activated, pathogenic T-cell line, and the ability of lymphocytes from orally
      tolerized animals to transfer resistance to tEAU shows that effector mechanisms
      can be inhibited by oral feeding as well as the afferent mechanisms reported here
      and elsewhere. Circulating levels of IgG specific for S-Antigen were not affected
      by feeding any of the peptides.

PMID- 1343766
TI  - Cytokine expression in labial salivary glands from patients with primary
      Sjogren's syndrome.
AB  - The presence and distribution of 7 cytokines was examined immunohistologically in
      labial salivary gland (LSG) specimens from patients with primary Sjogren's
      syndrome (SS) and control subjects. The cytokines interleukin (IL)-1 beta IL-6,
      tumor necrosis factor (TNF) alpha and interferon (IFN) gamma were identified in
      defined parts of LSG from patients but not in the corresponding parts of control
      glands: (a) LSG acinar epithelium expressed IL-1 beta, (b) blood vessels located
      in both normal LSG stroma and within lymphocytic infiltrates expressed IL-1 beta,
      IL-6 and IFN gamma, and (c) lymphocytic infiltrates expressed IL-1 beta, IL-6 and
      TNF alpha. All four cytokines were expressed by salivary ducts within both
      patient and control specimens, but with generally greater intensity in patients.
      IL-1 alpha, IL-4 and TNF beta (lymphotoxin) could not be detected in any of the
      specimens from patients or controls. The locations of cytokines in LSG suggests
      possible mechanisms of immunologically mediated parenchymal damage in primary SS.

PMID- 1343767
TI  - Mechanisms of complete Freund's adjuvant protection against diabetes in BB rats:
      induction of non-specific suppressor cells.
AB  - We have previously reported that a single injection of complete Freund's adjuvant
      (CFA) can prevent diabetes appearance in diabetes-prone (DP) BB rats. In this
      study, we investigated further the mechanism of CFA-induced protection from
      diabetes. We found that adoptive transfer of splenic cells from CFA-treated DP
      rats into young DP rats protected the latter from diabetes development. This
      suggested that CFA-induced protection from diabetes resulted from activation of
      regulatory (suppressor) cells. Cell mixing experiments in vitro indicated that
      CFA activated splenic cells with antigen-nonspecific suppressor activity
      (suppression of lymphoproliferative responses to lipopolysaccharide and to
      allogeneic splenic cells). Fractionation of splenic cells on Percoll revealed
      that the suppressor activity resided in low density cells relatively depleted of
      T-cells, B-cells, macrophages and NK cells. These results suggest that non
      specific (natural) suppressor cells in CFA-treated BB rats may be responsible for
      suppressing autoimmune responses and preventing insulitis and diabetes
      development.

PMID- 1343768
TI  - Thyroid-associated ophthalmopathy.
AB  - Thyroid-associated ophthalmopathy (TAO) is one of the most vexing problems in
      endocrinology but its relationship to thyroid autoimmunity is becoming more clear
      with the realisation that almost all patients with Graves' disease have this
      condition and almost all patients with ophthalmopathy have some form of thyroid
      involvement. This suggests cross reactivity between thyroid and retrobulbar
      antigens, of which one potential candidate has recently been cloned. Together
      with new information on predisposing factors and the important role of the
      retrobulbar fibroblasts, these developments shed new light on the aetiology and
      pathogenesis of this enigmatic disorder.

PMID- 1343769
TI  - The presence of autoantibody to lipocortin-I in autoimmune-prone MRL mice.

PMID- 1343770
TI  - Expression of the 90 kD heat shock protein in Behcet's syndrome.

PMID- 1343771
TI  - A muscle-specific actin gene from the Mediterranean fruit fly, Ceratitis
      capitata.
AB  - A characterization of an actin gene isolated from the genome of the Mediterranean
      fruit fly, Ceratitis capitata, including the complete sequencing of the coding,
      3' and 5' flanking regions of this gene and a partial cDNA was carried out. The
      partial cDNA was derived from the 3' untranslated region of the actin gene
      described here, and has been used to identify this gene uniquely. The DNA
      sequence data presented here, together with the pattern of expression exhibited
      by this gene during development, strongly support the interpretation that this is
      a muscle-specific actin gene. Peaks of expression are seen in tissues and during
      temporal phases of development where muscle differentiation is occurring. The
      derived protein sequence of the Medfly acting gene shows the highest degrees of
      similarity, 98.4 and 96.6% respectively, with the two muscle-specific actin genes
      79B and 88F from D. melanogaster. The Medfly actin gene also has a single
      intervening sequence, and an intron is found at the same position in the 79B and
      88F actin genes. In the coding region at the DNA level, 17.2 and 16.4% nucleotide
      differences, respectively, are observed between the Medfly actin gene and these
      same two D. melanogaster actin genes. The disparity between the amino acid and
      nucleotide comparisons can be explained, in part, by a high level of synonymous
      changes in the DNA sequence. In addition, despite the many similarities, codon
      usage appears to be very different between the actin genes of these species.

PMID- 1343773
TI  - Structure and sequence of the Cu, Zn superoxide dismutase gene of Chymomyza
      amoena: phylogeny of the genus and codon-use evolution.
AB  - We have cloned and sequenced the Cu, Zn superoxide dismutase gene of Chymomyza
      amoena. The coding sequence has the same length as in Drosophila species and in
      Ceratitis capitata. There are two introns, located at the same sites as in
      Ceratitis. The second intron is absent in Drosophila: this places Chymomyza
      outside the Drosophila lineage, contrary to proposals based on anatomical and
      other evidence. The nucleotide or amino acid distances support a phylogeny in
      which Ceratitis first branches off the common stem, then Chymomyza splits before
      the divergence of the two major Drosophila subgenera. The estimated divergence
      times are 58 million for Chymomyza-Drosophila; 48 million years for the
      Drosophila subgenera. During the intervening 10 million years, the Drosophila
      lineage lost the second intron and evolved distinct codon-preferences: the G + C
      use in the third coding positions is increased by 69% in Drosophila relative to
      Chymomyza or Ceratitis.

PMID- 1343772
TI  - Phylogeny of cytoplasmic incompatibility micro-organisms in the parasitoid wasp
      genus Nasonia (Hymenoptera: Pteromalidae) based on 16S ribosomal DNA sequences.
AB  - Cytoplasmic incompatibility results in embryo mortality in diploids, or all male
      offspring in haplodiploids, when individuals carrying different cytoplasmic
      factors are crossed. Cytoplasmic factors have been identified as intracellular
      micro-organisms. Microbe-induced cytoplasmic incompatibility is found in many
      insect taxa and may play a role in reproductive isolation between populations.
      Such micro-organisms cause bidirectional incompatibility between species of the
      parasitoid wasp genus Nasonia. The phylogenetic relationship of cytoplasmic
      incompatibility microorganisms (CIM) of different Nasonia species was analysed
      using their 16S ribosomal DNA (rDNA) sequence. Two 16S rDNA operons were detected
      in the CIM of each Nasonia species. Sequence analysis indicates that the Nasonia
      CIM are closely related and belong to the alpha group of the Proteobacteria.

PMID- 1343774
TI  - A Drosophila metallothionein promoter is inducible in mosquito cells.
AB  - Expression from a Drosophila metallothionein promoter (Mtn) was investigated in
      mosquito cells. Recombinant plasmids carrying a transcription unit comprised of
      the Escherichia coli beta-galactosidase gene (lacZ) fused to the metallothionein
      promoter were stably introduced into Aedes albopictus C6/36 cells. A low copy
      transformant containing approximately 60 copies of plasmid per cell, and a high
      copy transformant (1-2 x 10(4) copies/cell) were characterized. The expression of
      beta-galactosidase from the metallothionein promoter could be induced and
      controlled in this heterologous system, even when the copy number of introduced
      plasmid was several thousand.

PMID- 1343775
TI  - Distribution of split 5.8S ribosomal RNA in Diptera.
AB  - Although the 5.8S ribosomal RNA (rRNA) of most eucaryotes consists of 155-170
      nucleotides, in two dipterous species the 5.8S rRNA consists of two pieces, 123
      and 30 nucleotides in length. The distribution of split 5.8S rRNA was studied in
      other Diptera and the most closely related order Siphonaptera to learn the origin
      of split 5.8S rRNA. Four species of mosquitoes, Culex tritaeniorhynchus, Culex
      pipiens molestus, Aedes albopictus, Anopheles sp. (Culicidae) had a single 5.8S
      rRNA consisting of approximately 154 nucleotides. A flea Ctenocephalides felis
      (Siphonaptera: Pulicidae) also had a single RNA of approximately 158 nucleotides.
      A crane fly (Tipulidae). a midge Orthocladius akamusi (Chironomidae), a robber
      fly (Asilidae), and a house fly Musca domestica (Muscidae), on the other hand,
      had divided 5.8S rRNA as did a fruit fly Drosophila melanogaster (Drosophilidae)
      and a dark-winged fungus gnat Sciara coprophila (Sciaridae). Three hypotheses are
      proposed on the relationship between the evolution of the 5.8S rRNA and the
      phylogeny of Diptera.

PMID- 1343776
TI  - Expression of the chloramphenicol acetyltransferase gene in Aedes albopictus
      (C6/36) cells using a non-infectious Sindbis virus expression vector.
AB  - Genomic RNA was transcribed in vitro from the non-infectious Sindbis (SIN) virus
      expression vector (pTRCAT) and introduced into C6/36 (Aedes albopictus) cells by
      liposome-mediated transfections. The chloramphenicol acetyltransferase (CAT)
      polypeptide expressed within cells was detected by an indirect immunofluorescent
      assay directly into 24-well polystyrene tissue culture plates. Approximately 1 in
      1000 C6/36 cells showed fluorescence when the transfection was optimized. CAT
      enzyme activity was also assayed; in C6/36 cells CAT expression was detected as
      early as 8 h after transfection, peaked at 24 h, and could still be detected at 7
      days. At 24 h posttransfection each transfected C6/36 cell was calculated to
      express 1.3 x 10(7) CAT polypeptides.

PMID- 1343777
TI  - Characterization of a cDNA clone encoding a glycine-rich cuticular protein of
      Tenebrio molitor: developmental expression and effect of a juvenile hormone
      analogue.
AB  - The complete sequence of a cDNA clone, isolated from epidermal mRNA of Tenebrio
      molitor using a monoclonal antibody raised against an adult-specific cuticular
      antigen only present in the hard cuticle, was obtained after primer extension at
      the 5' end. From this cDNA sequence, the deduced protein encompasses 199 amino
      acids (including a signal peptide) with a total molecular weight of 20.7 kDa. The
      protein exhibits a bipartite structure: glycine-rich region located in its NH2
      terminal part and a carboxy-terminal domain sharing homologies with other
      cuticular proteins of Orthoptera, Diptera and Lepidoptera. In-situ hybridization
      analysis shows that the corresponding mRNA is present only in epidermal cells
      secreting the adult fibrous cuticle destined to become heavily sclerotized. In
      supernumerary pupae obtained after the application of the juvenile hormone
      analogue (JHA) to newly ecdysed pupae, the mRNA was undetectable, indicating that
      JHA can prevent the switch to the adult programme. However, in pupal-adult
      intermediates, obtained when JHA is applied later, the mRNA is detected.

PMID- 1343778
TI  - Gene structure of Bombyx mori larval serum protein (BmLSP).
AB  - To understand the molecular mechanisms of the larval-specific transcription of
      Bombyx mori larval serum protein (BmLSP), we isolated a clone of the BmLSP gene
      from a genomic library and sequenced a 3.5-kb fragment. An intron was found in
      the 5' noncoding region of the BmLSP gene. A putative transcription start point
      was determined by primer extension analysis. Genomic Southern hybridization
      showed that there is one copy of the BmLSP gene in a haploid genome. A database
      search revealed that the BmLSP gene has presumptive repetitive sequences found in
      other B. mori genes, the sequence homologous to ecdysone-responsive elements and
      a heptamer sequence found in storage protein genes.

PMID- 1343780
TI  - Transfection of cultured cells of the cotton boll weevil, Anthonomus grandis,
      with a heat-shock-promoter-chloramphenicol-acetyltransferase construct.
AB  - Expression of heat shock proteins (hsp) in the BRL-AG-3C cell line from the
      cotton boll weevil was examined. It was determined that the maximal expression of
      endogenous hsp occurred at 41 degrees C. Various transfection methods were then
      compared using this cell line in conjunction with a transiently expressed
      bacterial gene marker (chloramphenicol acetyltransferase) which was under the
      control of the Drosophila hsp 70 gene promoter. The cationic lipid preparation
      Lipofectin was found to be very efficient at transfecting the boll weevil cells.
      Polylysine and 20-hydroxyecdysone-conjugated polylysine were moderately
      effective, whereas polybrene and electroporation, under the conditions reported
      herein, were ineffective at transfecting this cell line.

PMID- 1343779
TI  - Sequence analysis of a mosquito ribosomal protein rpL8 gene and its upstream
      regulatory region.
AB  - The gene encoding Aedes albopictus ribosomal protein L8 was isolated using a cDNA
      probe. Based on the deduced amino acid sequence, rpL8 has a mass of 28,605 Da, a
      pI of 11.97, and contains 9.6% Arg and 11.9% Lys. The rpL8 gene spans 1229
      nucleotides, and contains three exons measuring 73, 150, and 648 nucleotides. The
      first intron is 293 nucleotides long and interrupts an 85-nucleotide untranslated
      leader sequence. The AUG codon is located 12 nucleotides downstream of the 5'-end
      of the second exon. Separating the second and third exon is a 65-nucleotide
      intron. The major transcription initiation site, identified by primer extension
      and polymerase stop reactions, mapped 378 nucleotides upstream from the AUG start
      codon; minor initiation sites were also detected. The DNA sequence upstream of
      the rpL8 gene was T-rich, but conventional TATA and CAAT boxes were absent. This
      is the first molecular analysis of a mosquito ribosomal protein gene.

PMID- 1343781
TI  - Genetic variability in the social bee Lasioglossum marginatum and a cryptic
      undescribed sibling species, as detected by DNA fingerprinting and allozyme
      electrophoresis.
AB  - DNA fingerprints (DNAfp) were obtained for three widely separated samples of bee
      related to Lasioglossum marginatum using the M13 sequence as a probe. Bee samples
      were obtained from France (three localities separated by at most 20 km), Greece
      and India. All European populations exhibited almost identical profiles with
      similarity indices (S) of over 98% within a French sample, 94% among Greek bees
      and 90% between Greek and French bees. The DNAfp profiles of Indian bees showed
      more polymorphism (intrapopulation S = 77%) and were quite dissimilar to the
      European samples (S = 55% and 56% to French and Greek samples, respectively). The
      similarity between populations separated by over 2000 km is higher than among
      unrelated individuals within a population in two other bee species and the tsetse
      fly. Data from allozyme electrophoresis shows parallel variation to that obtained
      with DNAfp and the genetic differences between Indian and European samples are
      strikingly large (Indian and European populations shared no alleles at 14 out of
      47 loci surveyed) such that no more than one species must be involved.
      Nonetheless, the samples are indistinguishable morphologically. We argue that
      chronically low effective population size in these species results in low levels
      of genetic variability and that this, combined with a genetic bottleneck during
      the speciation event and colonization of Europe, may have resulted in both the
      extremely low levels of DNAfp variation in European bees and the large number of
      fixed allelic differences between European and Indian samples.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1343782
TI  - Modulation of DNA-binding proteins in Locusta migratoria in relation to juvenile
      hormone action.
AB  - Using a gel mobility shift assay, protein factors have been identified that may
      participate in the transcriptional regulation of the juvenile hormone (JH)
      induced vitellogenin A (VgA) gene of the migratory locust. Two DNA-binding
      proteins were found that were modulated in correlation with VgA gene activity
      during normal reproductive cycles and experimental stimulation by an active JH
      analogue (pyriproxyfen). One of these, JH factor (JHF), may be a regulator of VgA
      and perhaps other JH-responsive genes. The second, mobile factor (MF), appears to
      have a more general role in cellular responses to external stimuli such as JH and
      wounding. JHF and MF may represent factors that act together with the JH receptor
      to regulate VgA gene transcription.

PMID- 1343783
TI  - The scientific production and international reputation of Lauro Travassos.

PMID- 1343784
TI  - Description of Trichuris travassosi n. sp. (Nematoda: Trichurinae) from a
      Brazilian rodent, by light and scanning electron microscopy.
AB  - A new species of a trichurid nematode Trichuris travassosi n. sp., recovered from
      a wild rodent in the State of Rio Grande do Sul, Brazil, is described and
      compared to T. myocastoris (Enigk, 1933) and their differentiation was on the
      basis of a detailed morphometrical study. Oryzomys nigripes (Olfers, 1818) is a
      new host record for the genus. The denomination spicular prepuce is proposed to
      designate the structure previously named spicular sheath and, conversely,
      spicular sheath to indicate the cuticle that covers the spicule.

PMID- 1343785
TI  - Experimental paragonimiasias: therapeutical tests with praziquantel--first
      report.

PMID- 1343787
TI  - The colonization of cartilage and ligaments by Trypanosoma cruzi.

PMID- 1343786
TI  - [Determination of thermal requirements of Stomoxys calcitrans (L.) (Diptera,
      Muscidae), under laboratory conditions].
AB  - The biology of immature stages of Stomoxys calcitrans (L.) was studied in the
      laboratory under four constant temperatures. The study was carried out in
      biological incubators at 20, 25, 30 and 35 degrees C; 65 +/- 10% relative
      humidity and 14 hours of photophase. The most favorable temperature for
      developing eggs, larval and pupal was 25 degrees C, while 35 degrees C proved to
      be harmful for a normal developing of S. calcitrans in larval stage. The
      incubation periods for egg were 69.90, 42.58, 26.10, 21.78 hours and 2.91, 1.77,
      1.08, 0.90 days at 20, 25, 30, 35 degrees C, respectively. The larval stage was
      18.40, 11.63, 8.55 days and, the pupal stage, 8.60, 4.54, 3.60 days at 20, 25, 30
      degrees C, respectively.. Threshold temperatures for males were a little higher
      than for females, however, this difference was lesser than 1 decree C. On the
      other hand, the quantity of energy (GD) for developing females was a little
      higher than for males.

PMID- 1343788
TI  - Ultrastructure of the adults of Bunostomium phlebotomum (Nematoda:
      Ancylostomatidae).
AB  - The morphology of the male and female of Bunostomum phlebotomum are described
      based on scanning electron microscope (SEM) observations. The attachment of the
      worms to the small intestinal mucosa and during the copula were observed.
      Structures of the buccal capsule and genital organs were also studied.

PMID- 1343789
TI  - [Comparative study of the male external genitalia of Triatoma neotomae Neiva,
      1911, and Triatoma nitida Usinger, 1939, (Hemiptera: Reduviidae)].

PMID- 1343790
TI  - [Sparganosis in some Brazilian vertebrates. Difficulties in the identification of
      Luheella (Spirometra) species].
AB  - Some species of Amphibia and Reptilia are listed as new hosts of spargana, from
      material deposited in the Helminthological Collection of Oswaldo Cruz Institute.
      It is discussed the difficulties in identifying the larvae (Sparganum) and also
      the identification of adults of Luheella species from South America. The
      histopathology induced by spargana in the liver of a species of Amphibia is
      briefly described.

PMID- 1343791
TI  - Fecundity of Biomphalaria straminea and B. glabrata in the laboratory: a 12-month
      comparative study.

PMID- 1343792
TI  - Superoxide dismutase from Trichuris ovis--inhibition by benzimidazoles and
      pyrimidine derivatives.
AB  - Three superoxide dismutase isoenzymes of different cellular location were
      detected in an homogenate of Trichuris ovis. Each of these molecular forms was
      purified by differential centrifugation and precipitation with ammonium sulphate,
      followed by chromatography on DEAE-cellulose and Sephadex G-75 columns. The
      activity levels of the two molecular forms detected in the mitochondrial (one
      cyanide sensitive Cu-Zn-SOD and the other cyanide insensitive Mn-SOD) were higher
      than that of the superoxide dismutase detected in the cytoplasmic fraction
      (cyanide sensitive Cu-Zn-SOD). All molecular forms present evident differences to
      the SODs contained in the host liver. Molecular mass and some of the physical and
      chemical properties of the enzyme was determined for all three molecular forms.
      An inhibitory effect on the SOD of the parasite an the host was detected with a
      series of compounds, some of which markedly inhibited parasite enzyme but not
      host enzyme.

PMID- 1343793
TI  - [Geopolitical distribution of the occurrence of Fasciola hepatica in Santa
      Catarina State, Brazil].
AB  - During 12 years feces samples from cows, water buffaloes, sheeps and goats were
      examined by sequential tamis filtration to show the occurrence of Fasciola
      hepatica eggs. The material came from 129 municipalities of Santa Catarina State,
      and 5 g of feces per animal were examined. The occurrence of F. hepatica was
      confirmed in 64.82% of the municipalities. Considering the host, F. hepatica was
      confirmed in goats from Florianopolis, Sao Jose, Sao Joao Batista and Guaramirim
      municipalities; in sheep from Brusque, Pomerode, Palhoca and Sao Jose; in water
      buffaloes from 9 and in cows from 86 municipalities. For this study, 13,762 feces
      samples were examined and in 3,814 the presence of eggs of F. hepatica was
      demonstrated. The percentage of occurrence for host species was 27.86 in cows,
      24.72 in water buffaloes, 16.92 in sheep and 15.66 in goats. By the results it
      was demonstrated that Itajai Valley at Southeast Hidrographic Basin, in Santa
      Catarina State is an endemic area of F. hepatica, even though Uruguai
      Hidrographic Basin was not referred as a geographical record for this parasite.

PMID- 1343794
TI  - Natural infection of wild rodents by Schistosoma mansoni. Parasitological
      aspects.
AB  - The evaluation of the role of rodents as natural hosts of Schistosoma mansoni was
      studied at the Pamparrao Valley, Sumidouro, RJ, with monthly captures and
      examination of the animals. Twenty-three Nectomys squamipes and 9 Akodon
      arviculoides with a schistosomal infection rate of 56.5% and 22.2% respectively
      eliminated a great majority of viable eggs. With a strain isolated from one of
      the naturally infected N. squamipes, we infected 75% of simpatric Biomphalaria
      glabrata and in 100% of albino Mus musculus mice. The adult worms, isolated from
      N. squamipes after perfusion were located mainly in the liver (91.5%) and the
      mesenteric veins (8.5%). The male/female proportion was of 2:1. The eggs were
      distributed on small intestine segments (proximal, medial and distal portions)
      and the large intestine without any significant differences in egg concentration
      of these segments. In A. arviculoides, the few eggs eliminated by the stools were
      viable and there was little egg retention on intestinal segments. Considering the
      ease to complete S. mansoni biological cycle in the
      Nectomys/Biomphalaria/Nectomys system under laboratory conditions, probably the
      same is likely to occur in natural conditions. In support to this hypothesis
      there are also the facts that human mansonic schistosomiasis has a very low
      prevalence in Sumidouro and endemicity among the rodents has not changed even
      after repeated treatments of the local patients. Based on our experiments, we
      conclude that N. squamipes has become a natural host of S. mansoni and possibly
      may participate in keeping the cycle of schistosomiasis transmission at Pamparrao
      Valley.

PMID- 1343795
TI  - Nectomys squamipes (Rodentia: Cricetidae) as an experimental model for
      Schistosomiasis mansoni.
AB  - Twenty specimens of Nectomys squamipes born in captivity, were infected with 500
      cercariae by the transcutaneous route. Coprologic examinations were carried out
      from the 5th to 23rd week after infection. On the 7th, 8th, 12th, 16th, and 23rd
      weeks the animals were sacrificed and perfused. The oogram was performed in
      segments of the small intestine (proximal, medial and distal portions) and the
      large intestine. The average pre-patent period was of 42 days. The average number
      of eggs varied from 350 on the 6th week, to 800 on the 13th. From the 14th week
      on, the average number of eggs eliminated was lower than 50 per gram of feces.
      The recovery of worms kept steady on the 7th, 8th and 12th week (16.85%; 15.45%
      and 11.95%), decreasing to 7.70% on the 16th week and 8.45% on the 23rd week. The
      proportion of male/female worms was about the same on the first two weeks, but
      from the 12th week on, the proportion was: 1.4/1 on the 12th week; 2.5/1 on the
      16th week and 1.8/1 on the 23rd week. These observations suggest that N.
      squamipes may be used as an experimental model for schistosomiasis mansoni, to
      which it develops resistance mechanism, useful for immunity studies.

PMID- 1343796
TI  - Vaccination in murine schistosomiasis with adult worm derived antigens--II.
      Protective and immune response in inbred mice.
AB  - Previous work in our laboratory, mainly focused the prospects of achieving
      resistance against Schistosoma mansoni infection with adult worm-derived antigens
      in the form of a soluble extract (SE). This extract obtained by incubation of
      living adult schistosomes in saline, contains a large number of distinct
      molecules and was actually shown to be significantly protective in different
      outbred animals models such as Swiss mice and rabbits. It thus appeared
      worthwhile to investigate the potential protective activity of SE in different
      inbred strains of mice, known to be highly susceptible to the infection. Herein
      we present data showing that DBA/2 mice, once immunized with SE acquire
      significant levels of resistance to a S. mansoni cercarial challenge. In
      addition, preliminary studies on the immune system of immunized animals revealed
      that, injection of SE caused no general imbalance of B or T cell responses.

PMID- 1343797
TI  - Report of Balanorchis anastrophus in Para State with surface topography by
      scanning electron microscopy.
AB  - Balanorchis anastrophus Fischoeder, 1901, from the reticulum of Bos taurus is
      reported for the first time in the State of Para, Brazil. The surface topography
      as revealed by scanning electron microscopy is presented.

PMID- 1343798
TI  - [Natural parasitism of buffaloes in Botucatu, SP, Brazil. III. Dynamics of
      gastrointestinal parasitism in cows and their calves].
AB  - Gastrointestinal parasitism of 24 buffalo cows before parturition, and post
      parturition, their infection and that of their respective calves during the
      following 30 weeks were studied. Willis, Hoffmann and whenever possible, the
      modified Gordon & Whitlock techniques were used for fecal examinations. Toxocara
      vitulorum eggs were the earliest forms encountered in calves feces, as follows:
      during the 1st week after birth, 58.33% of the calves were positive, and in the
      4th week, 100% of these animals were positive. Eggs of Strongyloides sp were in
      the 1st week after birth in two of the calves and in the 5th week, all for them
      were positive. The next parasites to appear were the Coccidia of which oocysts
      were detected in the feces of two calves in the 2nd week after birth, and 58.33%
      of the calves were positive for these in the 3rd week, and in the 6th week, all
      calves shed oocysts in their feces. On the other hand, eggs of Strongyloides were
      the last forms to appear in calves feces. However, despite their sporadic
      appearance in the feces, eggs of these parasites were observed continuously from
      the 11th week onwards, and at this point, the percentage of positive samples
      began to increase to reach its peak. Relatively to adult animals, eggs of T.
      vitulorum were observed in the feces of 11 cows, one or twice at most; eggs of
      Strongyloides sp were seen only once in the feces of four buffalo cows and eggs
      of Strongyloides in 21 out of 24 cows. Oocysts of Coccidia were observed in 16
      cows. Mechanisms of infestation of calves with these parasites are discussed.

PMID- 1343800
TI  - Cotylophoron Travassosi sp. n. (Trematoda--Paramphistomidae) from cattle.
AB  - A new species of the genus Cotylophoron (Trematoda--Paramphistomidae) -
      Cotylophoron travassosi sp. n.--is described. The measurements of the worm and
      its structures are compared with the valid known species.

PMID- 1343799
TI  - Enhancement of Leishmania amazonensis infection in BCG non-responder mice by BCG
      antigen specific vaccine.
AB  - Different patterns of cutaneous leishmaniasis can be induced when a challenge of
      alike dose of Leishmania amazonensis amastigotes in various inbred strains was
      applied. Two strains of mice, the Balb/c and C57BL/10J, showed exceptional
      susceptibility, and 10(6) amastigotes infective dose lead, to ulcerative
      progressive lesions with cutaneous metastasis and loss by necrosis of leg on
      which the footpad primary lesion occurred. Lesions were also progressive but in a
      lower degree when C3H/HeN and C57BL/6 were infected. Lesions progress slowly in
      DBA/2 mice presenting lesions which reach a discreet peak after 12 weeks, do not
      heal but do not ulcerate. DBA/2 mice is, therefore, a good model for
      immunomodulation. In attempt to determine the influence of BCG in vaccination
      schedule using microsomal fraction, DBA/2 became an excellent model, since it is
      also a non-responder to BCG. Vaccination of DBA/2 mice, receiving the same 10(6)
      BCG viable dose and 10 micrograms or 50 micrograms of protein content of
      microsomal fraction, lead to a progressive disease with time course similar to
      those observed in susceptible non-vaccinated C57BL/10J mice after 6 months of
      observation. An enhancement of infection in BCG non-responder mice suggests that
      use of BCG as immunostimulant in humans could be critical for both vaccination
      and immunoprophylactic strategies.

PMID- 1343801
TI  - [Bionomic studies of Dipetalogaster maximus (Uhler, 1894) (Hemiptera, Reduviidae,
      Triatominae). III. Population dynamics].
AB  - A population dynamics study of D. maximus was carried out under laboratory
      conditions (28 degrees C e 65% +/- 5% U.R.), and the methodology was the same
      that has been used for rearing these insects. In order to evaluate the population
      growth rate of this species, during a 24 months period, five colonies started
      with a couple recently emerged were observed. Each couple (a male and a female)
      was maintained in a glass container measuring 20 cm of diameter and 20 cm in
      height with filter paper on the bottom. The insects were monthly feeding with
      normal mice blood, and at this day the number of eggs, nymphal stages and adults
      was registered. All graphical representations of the populations growth showed
      the same shape. It was found that the average of nymphal stage represented 64.3%
      of the hole population whereas the oviposition curve showed to be inverse to this
      one (28.57%) a small percentage of adults was found: males 3.85% and females
      3.12%. In this study observations on the biological cycle, longevity and
      fertility rates were also carried out.

PMID- 1343802
TI  - Schizotrypanids: the occurrence of dermatitis in immunodeficient animals infected
      with Trypanosoma cruzi.
AB  - Congenitally athymic nude Balb/c (nu/nu) and their phenotypically normal adult
      and neonate littermates (nu/+), the C3H/HeN as well, were intraperitoneally
      infected with two strains (Y or CL) or Trypanosoma cruzi. The nude mice and the
      neonates developed a severe parasitaemia, the susceptible C3H/HeN also presented
      high level and adult Balb/c mice presented parasitaemia similar to that observed
      in outbred mice. Erythematous skin lesions were observed initially in infected
      athymic nude and neonates, being characterized by nests of amastigotes in the
      dermis; in C3H/HeN infected mice no nest of parasite was observed but a low-grade
      inflammatory reaction was seen. In adult Balb/c or OF1 outbred mice nest was
      found but discreet inflammatory reaction was observed in severe infections.

PMID- 1343803
TI  - Lamella formation and emigration from the water by a laboratory colony of
      Biomphalaria glabrata (Say) in a flow-through system.
AB  - Lamella formation and emigration from the water were investigated in juvenile
      Biomphalaria glabrata reared at two temperatures in aquaria with a constant water
      flow. Most snails (97.4%) reared at the lower temperature (21 degrees C) formed
      lamella at the shell aperture and emigrated from the water, whereas only 10.1%
      did so at 25 degrees C. Eighty percent of emigrations at 21 degrees C occurred
      within a period of 15 days, 70-85 days after hatching. A comparison of the
      studies done so far indicates that the phenomenon may be affected by the ageing
      of snail colonies kept in the laboratory and their geographic origin, rather than
      the rearing conditions. This hypothesis, however, requires experimental
      confirmation.

PMID- 1343804
TI  - Description of Raillietia flechtmanni sp. n. (Acari: Gamasida).
AB  - Raillietia flechtmanni sp. n. is described from the ear canal of its type host
      the domestic buffalo. The new species parasitizes cattle as well in Brazil.

PMID- 1343805
TI  - Preliminary investigations on transmission and life cycle of the ear mites of the
      genus Raillietia trouessart (Acari: Gamasida) parasites of cattle.
AB  - The life cycle of ear mites of the genus Raillietia Trouessart consists of egg,
      larva, proto- and deutonymph and adult. The proto- and deutonymph are free
      living, non feeding instars. The teneral adult is the transfer stage. The minimum
      period required for completion of the life cycle is approximately eight days.

PMID- 1343806
TI  - Prophylactic fluconazole and Candida krusei infections.

PMID- 1343807
TI  - Antiphospholipid antibodies and fetal loss.

PMID- 1343808
TI  - Gastrointestinal endoscopy.

PMID- 1343809
TI  - The Ingelfinger rule.

PMID- 1343810
TI  - On authorship and acknowledgments.

PMID- 1343811
TI  - Effects of restrictive handgun laws.

PMID- 1343812
TI  - Home monitoring of uterine activity.

PMID- 1343813
TI  - Acyclovir in chickenpox.

PMID- 1343814
TI  - Aspirin for cerebral transient ischemic attacks or minor ischemic strokes.

PMID- 1343815
TI  - A modification of the Cincinnati approach for obtaining adequate lengthening of
      the tendo achillis in the presence of severe equinus deformity.

PMID- 1343816
TI  - [The effect of granulocyte elastase inhibitor (urinastatin) vaginal suppository
      on patients with imminent premature delivery].
AB  - Cervical maturation, dilatation and uterine contraction in imminent premature
      delivery are closely related to chemical mediators from activated granulocytes
      which infiltrate into the cervix. It is known that urinastatin (urinary trypsin
      inhibitor, UTI) inhibits many kinds of chemical mediators from granulocytes and
      macrophages such as granulocyte elastase (elastase) and interleukin 1. We
      examined the effect of a UTI suppository on uterine contraction and the elastase
      level in cervical mucus in cases of imminent premature delivery. We treated 43
      cases of imminent premature delivery with tocolysis index 3 or 4 with 4 kinds of
      therapy: Group A (N = 12): ritodorine drop infusion therapy; Group B (N = 9):
      daily UTI suppository (1,000U) therapy; Group C (N = 14): daily UTI suppository +
      ritodorine drop infusion therapy; Group D: daily UTI suppository + ritodorine
      drop infusion + antibiotics (oral cepharosporine) therapy. The elastase level of
      cervical mucus before treatment was 0.76 +/- 0.40 micrograms/ml in group A, 0.93
      +/- 0.43 micrograms/ml in group B, 0.85 +/- 0.40 micrograms/ml in group C and
      0.90 +/- 0.41 micrograms/ml in group D. There was no significant difference
      between these groups. The elastase level in cervical mucus was 0.75 +/- 0.47
      micrograms/ml in group A, 0.27 +/- 0.35 micrograms/ml in group B, 0.27 +/- 0.33
      micrograms/ml in group C and 0.30 +/- 0.19 micrograms/ml in group D,
      respectively. The elastase level was decreased significantly in groups B, C and
      D. The time taken to depress uterine contraction was 65 +/- 66 min in group A,
      375 +/- 336 min in group B, 70 +/- 64 min in group C and 58 +/- 53 min in group
      D, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343817
TI  - IgG subclass deficiency associated with corticosteroids in obstructive lung
      disease.
AB  - IgG subclass levels were measured in three groups of adult patients with
      obstructive airways disease to discern the relationships among depressed IgG
      subclass levels, chronic corticosteroid use, and recurrent sinopulmonary
      infections. Group 1 consisted of patients with corticosteroid-dependent bronchial
      asthma, group 2 patients had corticosteroid-dependent chronic
      bronchitis/emphysema, and group 3 was comprised of asthma patients not requiring
      oral corticosteroids but associated with recurrent sinopulmonary infections. One
      or more IgG subclass deficiencies were noted in 66.7 percent of group 1, 46.7
      percent of group 2, and 6.7 percent of group 3. Significant differences were
      noted between groups 1 and 3 (p = .0008) and between groups 2 and 3 (p = .018),
      but not between groups 1 and 2 (p = .5). IgG1 deficiency was the most common
      subclass deficiency found; 14 (77.8 percent) of 18 patients with detectable
      subclass deficiency demonstrated IgG1 deficiency. In this study population, IgG
      subclass level deficiencies appeared to be secondary to long-term low-dose
      corticosteroid therapy.

PMID- 1343818
TI  - The allocation of leprosy patients into paucibacillary and multibacillary groups
      for multidrug therapy, taking into account the number of body areas affected by
      skin, or skin and nerve lesions.
AB  - In Nepal, the setting up and maintaining of reliable services for slit-skin
      smears has proven difficult. A clinical classification system for leprosy has
      therefore been developed to assist in the allocation of patients to either
      paucibacillary or multibacillary groups for the purpose of multiple drug therapy
      (MDT), using 9 body areas: head (1), arms (2), legs (2), trunk (4). Patients with
      more than two areas of the body affected are grouped as multibacillary (MB) and
      those with only one or two areas affected are paucibacillary (PB). Using a
      computer simulation model and the data of 53 patients registered at Green
      Pastures Hospital (GPH) in Pokhara and 703 field patients from the Western
      Region, different clinical classification systems were evaluated with regard to
      their sensitivity, specificity, and predictive value for MB or PB classification,
      as compared with the histological classification for the GPH cases and the
      bacteriological classification for the field patients. The sensitivity and
      specificity of the body area system in present use were 93% and 39%,
      respectively. The low specificity is due to MB overclassification. The
      sensitivity of the WHO classification system without skin smear facilities is 73%
      (the difference with the body area system is significant: p < 0.05, McNemar's
      test). Our histology findings confirm previous publications indicating that,
      while some borderline-tuberculoid (BT) patients may outwardly have a 'PB
      appearance' and be skin-smear negative, their nerve biopsy and sometimes skin
      biopsy may show a 'MB' picture. This is the first publication discussing a 'body
      area system' for the purpose described, including diagrams of the areas used. In
      Nepal it has proved easy to use and teach and its use may be justified in other
      control programmes which implement MDT, particularly if slit-skin smear services
      are unreliable or nonexistent.

PMID- 1343819
TI  - General dental practitioners' evaluation of the need for extraction of
      asymptomatic mandibular third molars.
AB  - Thirty general dental practitioners were asked to evaluate the need for
      extraction of asymptomatic mandibular third molars. Thirty-six mandibular third
      molars with equal distribution of angular positions, impaction status, males and
      females and age groups were selected. To estimate the consistency of the
      evaluation, the 36 cases were duplicated so that, in all, 72 teeth were
      evaluated. The number of molars proposed to be extracted by the observers varied
      from 0 to 26. There was no third molar which all observers agreed should be
      extracted. The two molars which most observers, 25 and 23 of altogether 30
      observers, proposed to be extracted were partially covered by soft tissue. The
      decision not to extract two molars was unanimous. Both of these were completely
      covered by bone tissue and positioned vertically. The mean overall intra-observer
      agreement for the therapeutical decision was 92%, with a range of 69-100%. The
      length of professional experience of the observer did not influence the
      evaluation whether or not to extract. We conclude that there is a great variation
      among general dental practitioners regarding their evaluation on the need for
      removal of asymptomatic mandibular third molars.

PMID- 1343820
TI  - Devic's neuromyelitis optica and Schilder's myelinoclastic diffuse sclerosis.
AB  - An adult patient developed both Devic's neuromyelitis optica and Schilder's
      myelinoclastic diffuse sclerosis, suggesting that these entities represent rare
      topographical and aggressive variants within the spectrum of multiple sclerosis.

PMID- 1343821
TI  - Identification, genetic analysis and characterization of a sugar-non-specific
      nuclease from the cyanobacterium Anabaena sp. PCC 7120.
AB  - A nuclease that could be recovered from the supernatant of cultures, as well as
      from cell-free extracts, of the cyanobacterium Anabaena sp. PCC 7120 was
      identified as a 29 kDa polypeptide by its ability to degrade DNA after
      electrophoresis in DNA-containing SDS-polyacrylamide gels. Some clones of a gene
      library of strain PCC 7120 established in Escherichia coli were found to produce
      the 29 kDa nuclease. The nucA gene encoding this nuclease was subcloned and
      sequenced. The deduced polypeptide, NucA, had a molecular weight of 29,650,
      presented a presumptive signal peptide in its N-terminal region and showed
      homology to the products of the nuc gene from Serratia marcescens and the NUC1
      gene from Saccharomyces cerevisiae. The NucA protein from Anabaena itself, or
      from the cloned nucA gene expressed in E. coli, catalysed the degradation of both
      RNA and DNA, had the potential to act as an endonuclease, and functioned best in
      the presence of Mn2+ or Mg2+. An Anabaena nucA insertional mutant was generated
      which failed to produce the 29 kDa nuclease.

PMID- 1343822
TI  - Allograft membranous nephropathy.

PMID- 1343824
TI  - Most diseases result from disturbances in intercellular signalling.

PMID- 1343823
TI  - An ethical approach to screening for human immunodeficiency virus.

PMID- 1343825
TI  - Purification and point-mutation analysis of human interleukin-2 (Ser-125).
AB  - A new type of IL-2(Ser-125) was purified by semi-preparative RP-HPLC, and its
      purity was analyzed with microbore HPLC, IEF, SDS-PAGE and capillary
      electrophoresis (CE). The N-terminal sequencing indicated the microheterogeneity
      of the N-terminus, i.e., N-Met(2/3) and N-Ala(1/3), which was identified with the
      results of CE and IEF. The amino acid sequence of the point mutated peptide
      confirmed the replacement of Cys-125 with Ser.

PMID- 1343826
TI  - Cloning and partial sequencing of the porcine growth hormone (pGH) gene from
      pituitary gland.
AB  - High molecular weight DNA was isolated from porcine pituitary gland, and a
      genomic library was constructed using lambda EMBL3 as cloning vector. Five
      positive clones were identified by in-situ hybridization with the full-length pGH
      cDNA as the probe. Dot-blot hybridization, restriction analysis, and Southern
      hybridization showed that one of the positive clones contained the entire pGH
      gene. A subclone that contained the upstream sequence from the SmaI site of pGH
      gene was identified, and part of it was sequenced. We also compared the sequence
      of our pGH gene with the corresponding sequence of the published pGH gene.

PMID- 1343827
TI  - Cloning, mapping, and sequencing of 3' and its flanking region of bovine alpha-s1
      casein gene.
AB  - A positive clone was isolated from a bovine genomic library in EMBL3 with the
      probe of alpha-s1 casein gene cDNA. The results from both restriction
      endonuclease digestion and Southern hybridization probed with the upstream and
      downstream fragments from the termination codon of bovine alpha-s1 casein gene
      cDNA suggested that the clone contained 3.5 kb downstream and 10.2 kb upstream
      fragments from the termination codon of alpha-s1 casein gene. Some divergences in
      restriction endonucleases sites, a few deletions, and many point mutations were
      found in introns and exons when compared with those which were published.

PMID- 1343828
TI  - Establishment of hybridoma cell line secreting specific monoclonal antibodies
      against turnip mosaic virus and analysis of properties of the McAb.
AB  - Monoclonal antibodies (McAb) of hybridomas derived from the fusing of the mouse
      splenocytes immunized by TuMV with BALB/c mouse myeloma cells (SP2/0-Ag14). Five
      kinds of hybridoma cell line were produced by indirect-ELISA screening and
      cloning three times with limiting dilution. Four kinds of hybridoma produced
      antibodies respectively reactive to TuMV C1, C3, C4 and C5. One kind was reactive
      to all five strains of TuMV. In indirect-ELISA and sandwich-ELISA tests, TuMV
      specific monoclonal antibodies did not react with CaMV, CMV, TMV, PVX, and PVY.
      Antibody titers of ascitic fluids were about 1:256,000 to 2,048,000 in indirect
      ELISA. The biological, physical, and chemical properties of the hybridoma cell
      lines and McAb were identified. The identification of TuMV strains, the
      specificity and stability of McAb, the coat proteins, and the antigenic site of
      TuMV were discussed and analyzed with SDS-PAGE and western-blotting.

PMID- 1343829
TI  - Effects of ammonium and lactate on hybridoma cell growth and metabolism.
AB  - The effects of ammonium and lactate at different concentrations on the growth of
      2F7 hybridoma cells, involving glucose consumption, lactate accumulation and cell
      viability, are investigated. The results suggest that growth inhibition occurs at
      2.5 mM ammonium and 2.5 mg/ml lactate, and that severe inhibition occurs at 5 mM
      ammonium and 5.0 mg/ml lactate.

PMID- 1343830
TI  - Metabolic regulation of pigment formation of Onosma paniculatum cultured cells.
AB  - The pigment yields of Onosma paniculatum callus and suspension cultured cells
      were increased 5.5 and 8.1 fold of that of the control respectively, when 10(-5)
      M of copper ion was added into the medium. The pigments synthesis was also
      stimulated greatly when 10(-5) M of L-phenylalanine was added into the medium and
      the cells were cultured for twenty-one days. The maximum yield of pigments was
      obtained when 10(-6) M of ascorbic acid was added to the medium.

PMID- 1343831
TI  - Partition coefficient of luciferase from photobacteria in PEG/salt two aqueous
      phase system.
AB  - The relationship between the logarithmic partition coefficient (K) of luciferase
      of photobacteria and PEG MW in the PEG/salt two aqueous phase system was shown to
      be a linear function. The hydrophilic PEG of lower MW facilitated the partition
      of luciferase into the top PEG-riching phase and gave a higher K value, while PEG
      of higher MW, its hydrophobic characteristic, made more enzyme partition into the
      bottom salt-riching phase and lower K value was obtained. In the PEG/trivalent
      salt system, such as phosphate and citrate, there was a turning-point on the
      linear relation between the log K and the PEG MW, but which never appeared if a
      divalent salt such as sulfate, succinate or tartrate was used in the system. When
      the system was composed of homogeneous PEG and ammonium sulfate, the K value was
      increased with the increment of the salt concentration, but after the salt
      concentration had reached at certain level, the K value was uninfluenced. When
      two kinds of PEG with different MW were used in this system a minimal K value
      appeared at certain concentration of ammonium sulfate, and the K value was raised
      when the salt concentration was either increased or decreased. Neither the
      proportion of the two kinds of PEG nor their total concentration used in the
      system showed any effect on the above patterns, although the K value may give
      some corresponding changes. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343832
TI  - Construction of hybridomas secreting monoclonal antibody against sweet potato
      feathery mottle virus and use of antibody for detection of SPFMV.
AB  - Two hybridomas stably secreting monoclonal antibodies (McAb) against sweet potato
      feathery mottle virus (SPFMV) were constructed by fusing mouse myeloma (Sp2/0
      Ag14) with mouse splenocytes immunized with SPFMV-LF. The McAb secreted by the
      two hybridomas specifically reacted with both SPFMV-LF (China strain) and SPFMV
      RC (American strain) in dot-blot-ELISA. A large amount of McAb was produced with
      BALB/c mice. The titer of hybridoma cultured supernatant was 1:256, and that of
      the ascitic fluids was 1:1 x 10(4); and the immunoglobulins of McAb were IgG2a
      and IgG3 respectively. The detection of SPFMV-infected sweet potato plants with
      McAb confirmed that the McAb obtained in this test were desirable for large-scale
      routine surveys of SPFMV. This study on construction of hybridomas and detection
      of SPFMV using McAb is the first report in the world.

PMID- 1343833
TI  - Neuropathology of immunosuppression.
AB  - Traditionally, the brain has been considered an "immunologically privileged"
      organ. Under normal conditions, the blood-brain barrier (BBB) is highly effective
      in preventing both cellular and humoral constituents of the blood from entering
      the brain parenchyma. In certain pathological conditions, such as viral
      infections and demyelinating disorders, the BBB may become altered, activated T
      cells and monocytes may gain access to the brain parenchyma, and microglia may
      assume the functions of antigen-presenting cells and macrophages. Naturally
      occurring or clinically-induced immunosuppression may dramatically alter various
      cellular and/or humoral aspects of the immune system. Consequently, the brain may
      become susceptible to disorders that would otherwise be excluded or may develop
      more severe manifestations of diseases, such as certain infections. This review
      considers the neuropathologic aspects of various conditions that may be
      encountered in the setting of both acquired and inherited immunosuppression. The
      major categories include infectious, neoplastic, vascular, and metabolic
      disorders. The review also briefly addresses the neuropathology of complications
      of chemotherapeutic agents, radiotherapy, and organ transplantation inasmuch as
      they often occur in the clinical setting of acquired immunosuppression.

PMID- 1343834
TI  - Dominant and recessive molecular changes in neuroblastomas.
AB  - Of all human tumors, neuroblastomas bear the most prominent genetic changes.
      Amplifications and deletions of chromosomal DNA can be identified by light
      microscopy on chromosomal spreads of neuroblastoma cells with remarkable
      frequency and consistency. Consequently, extensive studies have been undertaken
      to elucidate the molecular basis of these cytogenetic changes. A rich body of
      information has accumulated on the role played by dominant oncogenes and
      recessive tumor suppressor genes in the pathogenesis of this disease. Most
      notably, it was found that amplification of N-myc is responsible for the presence
      of double minutes and homogeneously staining regions in neuroblastoma
      chromosomes. It has also been discovered that N-myc amplification is a prognostic
      sign of malignancy. More recently, recessive genetic alterations in
      neuroblastoma, such as deletion of putative tumor-suppressing genes have received
      increasing attention, and considerable efforts are being made to identify such
      genetic elements. Finally, the susceptibility of neuroblastoma cells to
      differentiating stimuli has made them a popular in vitro system for
      neurobiological and pharmacological research. The need for suitable in vivo
      systems has spurred the development of several animal models employing tumor
      viruses and transgenic technologies.

PMID- 1343835
TI  - Hypoxic-ischemic brain injury of the newborn--statement of the problem and
      overview.

PMID- 1343836
TI  - Anatomical features of the developing brain implicated in pathogenesis of hypoxic
      ischemic injury.
AB  - The developing nervous systems is subject to damage from lack of vital substances
      necessary for normal maturation and function as well as from trauma or a variety
      of toxins and infectious agents. By far, the most important of these is
      inadequate oxygen delivery to the fetus in utero, and/or during the intrapartum
      and/or early neonatal period. Many types of lesions have been described under the
      rubric of hypoxic-ischemic encephalopathy, a major proportion of which are found
      only in the immature nervous system and essentially are never seen later in life.
      Moreover, a large number are primarily hemorrhagic rather than ischemic in
      character. The unique character and distribution of these lesions results from a
      collision of the changing anatomy of the developing nervous system and
      pathophysiological factors afflicting the immature organism. Whereas the majority
      of hypoxic-ischemic lesions in the fetus/neonate fall into this group,
      abnormalities characteristically found in the mature nervous system are also
      seen. Recognition of the anatomic and physiological features peculiar to the
      developing nervous system will assist in diagnosis of hypoxic-ischemic damage
      peculiar to the fetus and neonate.

PMID- 1343837
TI  - Effect of cerebral blood flow and cerebrovascular autoregulation on the
      distribution, type and extent of cerebral injury.
AB  - Global cerebral blood flow (GCBF) is low in the human neonate compared to the
      adult. It is even lower in mechanically ventilated, preterm infants: 10-12 ml/100
      g/minute, a level associated with brain infarction in adults. The reactivity,
      however, of global CBF to changes in cerebral metabolism, PaCO2, and arterial
      blood pressure is normal, except following severe birth asphyxia, or in
      mechanically ventilated preterm infants, who subsequently develop major germinal
      layer hemorrhage. The low level of cerebral blood flow (CBF) matches a low
      cerebral metabolism of glucose and a relatively small number of cortical synapses
      in the perinatal period. It has not been possible to define a threshold for GCBF
      below which electrical dysfunction or brain damage occurs (such as white matter
      and thalamic-basal ganglia necrosis). Three explanations for the lack of clear
      relation between GCBF and electrical brain activity of the preterm infant must be
      examined more closely: 1) low levels of CBF are adequate; 2) GCBF does not
      adequately reflect critically low perfusion of the white matter, and 3) acute
      white matter ischemia does not result in electrical silence. Two clinical
      patterns of brain damage following asphyxia may be explained by changes in the
      blood flow distribution induced by asphyxia: brainstem sparing and parasagittal
      cerebral injury. Hours to days after severe asphyxia, a state of marked global
      hyperperfusion may prevail. It is associated with poor neurological outcome and
      may be an entry point for trials of interventions aiming sat blocking the
      translation of asphyctic injury to cellular death and tissue damage.

PMID- 1343838
TI  - Cerebral carbohydrate and energy metabolism in perinatal hypoxic-ischemic brain
      damage.
AB  - Cerebral hypoxia-ischemia remains a major cause of acute perinatal brain injury.
      Research in experimental animals over the past decade has greatly expanded our
      knowledge of those oxidative events which occur during a hypoxic-ischemic insult
      to the brain, as well as those metabolic alterations which evolve during the
      recovery period following resuscitation. The available evidence suggests that
      hypoxia alone does not lead to brain damage, but rather a combination of hypoxia
      ischemia or isolated cerebral ischemia is a necessary prerequisite for tissue
      injury to occur. Furthermore, hypoxia-ischemia severe enough to produce
      irreversible tissue injury is always associated with major perturbations in the
      energy status of the perinatal brain which persists well into the recovery
      period. The lingering energy depletion sets in motion a cascade of biochemical
      alterations that are initiated during the course of the insult and proceed well
      into the recovery period to culminate in either neuronal necrosis or infarction.
      Unlike the adult, where glucose supplementation prior to or during hypoxia
      ischemia accentuates tissue injury, glucose treatment of perinatal animals
      subjected to a similar insult substantially reduces the extent of tissue injury.
      The mechanism for the age-specific effect of glucose on hypoxic-ischemic brain
      damage is discussed in relation to pathogenetic mechanisms responsible for the
      occurrence of permanent brain damage.

PMID- 1343839
TI  - Excitatory amino acids contribute to the pathogenesis of perinatal hypoxic
      ischemic brain injury.
AB  - A large body of experimental evidence indicates that over-activation of
      excitatory amino acid (EAA) receptors may mediate irreversible neuronal injury in
      a variety of pathologic settings including cerebral ischemia, and that the
      developing brain may be particularly susceptible to the adverse effects of EAA
      receptor overactivation. In this article, we review current information about EAA
      receptor pharmacology and EAA neurotoxicity in the immature brain, and summarize
      recent experimental data indicating that EAA contribute to the pathogenesis of
      perinatal hypoxic-ischemic brain injury.

PMID- 1343840
TI  - Heat shock proteins in hypoxic-ischemic brain injury: a perspective.
AB  - There is much to suggest that the induction of heat shock protein synthesis is an
      important response to injury and stress in the brain. The role of heat shock
      proteins in neurological disease has been approached from two points-of-view.
      First, the induction and synthesis of specific proteins after brain cell injury
      provide a window through which insight on the regulation of gene expression in
      pathological tissue can be obtained. These studies have broad implications for
      understanding pathophysiological mechanisms of disease. Second, putative cell
      protective effects of heat shock proteins in brain tissue provide insight into
      biochemical mechanisms of selective neuronal vulnerability. These studies have
      extremely important clinical implications since cell sensitivity to injury can
      seemingly be modified. The role of heat shock proteins in hypoxic-ischemic brain
      injury is discussed forthwith.

PMID- 1343841
TI  - International Titisee Conference on Neuroimmune Networks: cell-cell communication
      and response to injury and regeneration, Titisee, Germany, March 4-8, 1992.

PMID- 1343842
TI  - Imaging and movement of iron-oxide-bound antibody microparticles in brain and
      cerebrospinal fluid.
AB  - Therapy with monoclonal antibody conjugates has been proposed for patients with
      malignant intracranial tumors and meningeal carcinomatosis. One obstacle to
      successful immunotherapy has been the inability of adequate quantities of
      antibody to reach and bind malignant cells. The use of superparamagnetic antibody
      microparticles offers a potential solution to the problem of inadequate antibody
      delivery. In this report, studies of the imaging characteristics and magnetically
      induced movement of iron oxide-bound antibody (IOAb) microparticles [BioMag] are
      described. 1 mg/ml IOAb was readily visualized using conventional CT scan
      technique, but produced image artifacts on MRI. Rapid movement of IOAb in vitro
      was noted to occur in response to a magnetic field gradient. This property was
      exploited in in vivo studies using laboratory animals. IOAb injected into the
      intrathecal space of sedated rats could be transported through the CSF and
      localized to the medial aspect of one cerebral hemisphere or the other, using an
      external magnet. Construction of specific microparticles may allow for improved
      delivery of therapeutic substances to specific sites within CSF pathways.

PMID- 1343843
TI  - Modulation of protein kinase C activity by palmitoyl esters of maltose.
AB  - Mixtures of maltose palmitates containing predominantly maltose tetrapalmitate
      (designated MTP) possess immune potentiating and antitumor properties. Immune
      potentiation derives from macrophage activation and B lymphocyte mitogenicity and
      antitumor action from anti-angiogenic activity. Their mode of action at the
      cellular level is not known. Since high performance liquid chromatography (HPLC)
      provided purified maltose palmitates, we tested whether they individually and as
      a mixture could modulate activity of protein Kinase C (PKC), an enzyme implicated
      in mitogenic and release reactions. MTP activated crude lymphocyte and purified
      brain PKC in the absence of phosphatidyl serine (PS). It also augmented labeled
      dibutyryl phorbol (PDBu) binding to the brain enzyme in the absence of
      phospholipid. HPLC purified maltose tetrapalmitates (two isomers) were insoluble
      in aqueous solvent, and activated PKC slightly after incorporation into PS
      liposomes. Purified maltose di- and tri-palmitates were inhibitory to the enzyme.
      The activation of PKC was, therefore, due to higher saturated maltose palmitates,
      well dispersed by less substituted maltose palmitates acting as emulsifiers.

PMID- 1343844
TI  - Metabolism of benzo[a]pyrene in human skin xenografts.
AB  - Although a human neonatal foreskin graft to a nude mouse has been shown to be
      morphologically intact for several months after establishment, the feasibility of
      using this system for carcinogenesis studies has not been widely investigated. In
      this study, we have investigated the metabolism of benzo[a]pyrene (BaP) in human
      skin xenografts after the topical application of different concentrations of
      [3H]BaP (0.5 microgram-10.0 micrograms and 20 muCi/graft) for 2 h and 1.0
      micrograms [3H]BaP for various intervals of time up to 4 h. Significant amounts
      of different organic solvent soluble metabolites were observed in all the
      different samples. The increase in the amounts of the organic solvent soluble
      metabolites was linear over the 0.5 microgram to 5.0 micrograms/graft range. When
      1.0 microgram [3H]BaP was applied to each graft, the maximum production of the
      organic solvent soluble metabolites was observed 10 minutes after treatment and
      it then decreased with time. Diols were the major metabolites detected in each of
      the experiments, followed by phenols, and then tetrols. The levels of water
      soluble glucuronide and sulfate conjugates were almost equivalent for each
      treatment over the same range of application of BaP per graft. The combined
      levels of these conjugates and the non-extractable organic soluble metabolites in
      the residue, generally ranged between 7-24% of the total metabolites in the
      various experiments.

PMID- 1343845
TI  - Regulation of M2-type pyruvate kinase from human meningioma by allosteric
      effectors fructose 1,6 diphosphate and L-alanine.
AB  - In the present study the mechanism of action of M2-type pyruvate kinase from
      human meningioma in the simultaneous presence of fructose 1,6 diphosphate and L
      alanine was investigated. Purified pyruvate kinase from human meningioma was
      allosterically inhibited by L-alanine with respect to substrates
      phosphoenolpyruvate and ADP. The inhibitory effects of L-alanine was partially
      removed by fructose 1,6 diphosphate. The purified enzyme was slightly susceptible
      to ATP inhibition.

PMID- 1343846
TI  - Mixed function oxidase demethylase and dealkylase activity in an electromagnetic
      field.
AB  - In contrast to the increase in reaction rate of microsomal NADPH-cytochrome-P450
      reductase activity resulting from low-level microwave perturbation (reported
      earlier) transformations involving the entire MFO-pathway were inhibited by a
      microwave field. Dealkylation of 7-ethoxycoumarin was inhibited 25% and
      demethylation of p-nitroanisole was inhibited 40% when the reaction was carried
      forward in a 9.14 GHz CW field. Microsomal preparations from the liver of mature
      chickens had enzymic characteristics (kinetic constants, inhibitor-response
      spectrum) for these substrates similar to those reported for rodent and human MFO
      complex.

PMID- 1343847
TI  - Sialic acid levels in various types of cancer.
AB  - Serum or plasma total sialic acid (TSA) and lipid bound sialic acid (LSA) are
      useful markers for human cancer. In this study, sialic acid levels have been
      demonstrated in various types of human cancer including brain, thyroid and
      Hodgkin's. TSA was found to be significantly elevated in various human brain
      tumors, especially in the microsomal fraction. Also serum and tissue LSA levels
      indicated significant increases when compared to the normals in various brain and
      thyroid tumors. TSA levels were significantly higher in the plasma and leucocyte
      in patients with Hodgkin's. The results show that sialic acid can be advisable as
      a beneficial marker for detecting malignancies. But it can not be used as a
      criteria for identifying tumor types.

PMID- 1343848
TI  - Spin-trapping of free radicals during phthalocyanine photosensitization of
      lymphoma cells in vitro.
AB  - Spin-trapping and electron spin resonance (ESR) spectroscopy were used to detect
      free radicals generated during light exposure of lymphoma cells sensitized in
      vitro by metallotetrasulfophthalocyanines (Al-PcS4 and Zn-PcS4). 5,5-dimethyl-1
      pyrroline-1-oxide (DMPO) and alpha-phenyl-beta-tert-butylnitrone (PBN) were used
      as spin-trapping agents. Hydroxyl radical spin-adducts were detected under
      conditions of both extracellular and intracellular photosensitization. In
      addition, organic radicals of different origin and/or variable yields were
      trapped, depending on the photosensitization conditions and the spin-trap used.
      For comparison, analogous experiments were carried out with another tumor
      localizing photosensitizer, Photofrin II.

PMID- 1343849
TI  - Stimulation of amino acid efflux from cells by extracellular serine.
AB  - P388 (murine) and CEM (human) leukemia cells were exposed in vitro to a serine
      deprived medium. Cultivation was carried out at 37 degrees C, 5% CO2.
      Proliferation assay was conducted with a RPMI 1640 medium (control) and a serine
      deprived medium for 3 days. The deprivation of serine reduced the proliferation
      of both cells, and the necessity of serine for the cell proliferation was thus
      recognized. The effects of the substance on the level and pattern of
      intracellular amino acids were observed. P388 cells exposed to serine-deprived
      medium for 3 h were then transferred to the control medium. The cellular amino
      acid levels were determined at the time of medium change and 1, 2, 3 h
      thereafter. Serine-deprivation improved intracellular amino acids in comparison
      with those from control, and the medium change to control reduced their levels.
      Therefore, extracellular serine appeared to regulate the efflux of amino acids
      from cells. This suggests that serine-deprivation may be useful for anticancer
      drug retention in the cells.

PMID- 1343850
TI  - Radioprotective properties of ATP and modification of acid phosphatase response
      after a lethal dose of whole body p(66MeV)/Be neutron radiation to BALB/c mice.
AB  - The intraperitoneal administration of exogenous ATP prior to a lethal dose (7 Gy)
      of whole body neutron irradiation increased the radioresistance of BALB/c mice.
      This radiation used the beam from a neutron therapy facility produced by the
      reaction p(66 MeV)/Be. Survival of the mice, determined 7 days post-irradiation
      as the endpoint, was increased from 26% to 86% by the action of the exogenous
      ATP. Furthermore, the response of acid phosphatase activity as an indicator of
      the acute radiation effects showed a marked augmentation in both tissues studied,
      testes and small intestine. The activity of the enzyme after neutron irradiation
      with prior administration of ATP showed smaller increases when compared with the
      increases observed after neutron irradiation alone. This implies that exogenous
      ATP reduces the effect of the lytic enzyme and, hence, damage. Finally, changes
      were observed in the activity of acid phosphatase in the testes and intestine
      with different concentrations of exogenous ATP. In both tissues there was a
      monotonic decrease in the activity of the enzyme with increase of the
      concentration of exogenous ATP administrated before radiation. These results
      reflect the protective ability of exogenous ATP as an adaptive defence mechanism
      to reduce radiation damage in normal tissues after a lethal dose of neutron
      radiation.

PMID- 1343851
TI  - The fluidity of DOPC bilayers and membrane fractions prepared from murine
      plasmacytoma cells is unchanged after incorporation of pristane (2,6,10,14
      tetramethylpentadecane) as assessed by fluorescence polarization analysis.
AB  - The nature of the plasmacytomagenic activity of pristane (2,6,10,14
      tetramethylpentadecane) is poorly defined. However, evidence for tumor promoting
      properties of pristane has recently come forward that includes direct cellular
      effects on B lymphocytes; i.e., the plasmacytoma precursor cell. Bly et al.
      (Cancer Biochem. Biophys. 11, 1990, 145-154) observed changed membrane fluidities
      in lymphocytes after administration of pristane in vivo. We measured steady-state
      fluorescence polarization using DPH (1,6-diphenyl-1,3,5-hexatriene) and APCL (1
      acyl-2-[12-(9-anthryl)-11-trans-dodecenoyl]-sn-glycero-3- phosphocholine) as
      probes in DOPC (L-alpha-dioleoylphosphatidylcholin) model membranes and membrane
      fractions derived from plasmacytoma cells after incorporation of pristane in
      vitro. In a previous investigation, we verified the in vitro uptake of pristane
      into DOPC bilayers under the conditions employed here (Gawrisch and Janz,
      Biochim. Biophys. Acta 1070, 1991, 409-418). However, neither in DOPC bilayers
      nor in plasmacytoma membrane fractions could we detect changes in fluorescence
      polarization after in vitro incorporation of pristane within reasonable error
      limits. Therefore, we suggest that the observed alterations in membrane fluidity
      in lymphocytes from pristane-treated animals are the indirect result of the in
      vivo treatment but not a direct effect of pristane on membrane fluidity.

PMID- 1343853
TI  - The E. Graeme Robertson Lecture. Interesting neurological syndromes.

PMID- 1343852
TI  - Effects of diabetes and insulin on phosphoinositide metabolism in R3230AC mammary
      tumors.
AB  - The effects of diabetes and insulin administration on certain aspects of
      phosphoinositide metabolism in R3230AC mammary tumors were studied in vivo. Three
      weeks after diabetes was induced by streptozotocin, [3H]myoinositol incorporation
      into PI, PIP and PIP2 was increased in R3230AC tumors, whereas the formation of
      [3H]IP, [3H]IP2 and [3H]IP3 was decreased. Administration of protamine zinc
      insulin (3IU, twice daily, for 3 days) to diabetic rats decreased [3H]myoinositol
      incorporation into phosphoinositides and inositol phosphates in these mammary
      tumors. The R3230AC tumor from insulin-treated diabetic hosts had lower levels of
      unmetabolized [3H]-myoinositol compared to tumors from diabetic animals.
      Enzymatically-dissociated tumor cells from insulin-treated animals displayed
      decreased myoinositol transport in vitro. These findings suggest that the insulin
      induced decrease in the turnover of inositol lipids in vivo in R3230AC mammary
      tumors could have resulted from the decreased level of [3H]myoinositol in these
      cells.

PMID- 1343854
TI  - History of neurology in Australia.

PMID- 1343855
TI  - Vigabatrin--plasma enantiomer concentrations and clinical effects.
AB  - Plasma concentrations of the [R]- and [S]- enantiomers of the new anticonvulsant
      vigabatrin were measured by an enantiospecific gas-liquid chromatographic assay
      in a group of therapy-resistant epileptic patients in whom racemic vigabatrin was
      added to their existing antiepileptic drug regimens. The peak plasma
      concentrations of the biologically active [S]-enantiomer of vigabatrin were
      correlated with those of the [R]-enantiomer, with drug dose, seizure frequency
      and change in score on various tests of psychological function administered prior
      to and when the subjects were under steady-state conditions following vigabatrin
      therapy. Plasma [S]-vigabatrin concentrations correlated with drug dose, [R]
      vigabatrin concentration and change in score of certain psychological tests
      reflecting verbal memory, recall and speed of information processing. No definite
      pharmacokinetic interactions were detected, though plasma phenobarbitone
      concentrations tended to fall during vigabatrin administration. There were too
      few data to assess the relation between [S]-vigabatrin concentrations and seizure
      frequency.

PMID- 1343856
TI  - Predicting survival after stroke: experience from the Perth Community Stroke
      Study.
AB  - Survival is the most fundamental measure of the outcome from stroke, the
      magnitude of the burden being strongly reflected in case-fatality and survival
      rates. Although the literature is rich with follow-up studies examining survival
      after stroke, most are based on selected series of patients and factors which
      correlated with time to death have usually been determined in univariate
      analyses. We examined the factors associated with a high risk of death during the
      acute phase of stroke. Analyses were based on data from a population based study
      of acute cerebrovascular disease undertaken in Perth, Western Australia, during
      an 18 month period 1989-1990. Using logistic regression modelling techniques only
      2 factors, severe loss of consciousness, odds ratio 14.7 [95% confidence limits
      (CL), 4.0-53.6], and severe paresis, odds ratio 7.2 [95% CL, 1.6-32.0],
      independently predicted death by 28 days after the onset of stroke. The
      implication is that 2 simple measures, level of consciousness and motor power,
      may help direct management. Furthermore, age is not an independent risk factor
      for death early after stroke. Therefore the elderly should not be denied therapy
      purely on the basis of their age.

PMID- 1343857
TI  - Thrombolytic therapy in vertebrobasilar occlusion.
AB  - Since 1983 at the Alfred Hospital 4 patients with thrombotic or embolic
      vertebrobasilar occlusions have been treated with intra-arterial streptokinase
      (SK) infusions for the effects of persisting brainstem ischaemia despite
      anticoagulation with heparin. In 3 cases there was immediate and dramatic
      neurological improvement, in all cases associated with arteriographically
      demonstrated reperfusion of a blocked vessel. Two of these patients suffered
      further thromboembolic vertebral or basilar artery occlusions (3 days and 2 years
      later) but recovered fully without further thrombolytic therapy. The other
      patient was given intra-arterial SK 12 days after an apparently completed
      brainstem stroke: the therapy failed to cause reperfusion of a vertebral
      occlusion or produce any clinical improvement. Complications from the therapy
      were nausea requiring the termination of the SK infusion in one case, easily
      controlled bleeding from a recent surgical wound, and a clinically insignificant
      haemorrhagic transformation of cerebellar infarction in a third. The benefits of
      thrombolytic therapy in vertebrobasilar ischaemia and the dose of streptokinase
      required are discussed.

PMID- 1343858
TI  - Confounding factors in non-invasive tests of neurovascular function in diabetes
      mellitus.
AB  - Disturbances of neurovascular function in the extremities may occur in patients
      with diabetes mellitus, exposure to toxic substances and chronic exposure to
      vibrating hand tools, as well as in Raynaud's phenomena. In these conditions
      symptoms of paraesthesia, finger numbness and blanching occur, so nerve
      conduction studies, vibration and temperature threshold measurements and
      neurovascular function tests are used for objective assessment of neurological
      dysfunction. The aim of the present study was to examine some factors which may
      confound quantitative neuro-vascular function measurements if used to assess
      neuropathy in diabetics. All subjects were consenting volunteers without exposure
      to known neurotoxic chemicals. The 5 groups were (a) healthy non-diabetic
      subjects not exposed to vibration (n = 10, mean age 52.3 yrs) (b) 2 insulin
      dependent and 8 non-insulin dependent diabetic subjects with a mean of 6 years
      treatment (n = 10, mean age 55.7 yrs) (c) maintenance employees exposed to high
      frequency pneumatic hand tools (n = 10, mean age 52.2 yrs) (d) subjects who were
      not diabetic or exposed to vibrating tools, but were being treated with the ACE
      inhibitor enalapril 20 mg daily for hypertension (n = 5, mean age 54 yrs) (e)
      subjects who had smoked more than 10 cigarettes daily for at least 15 yrs (n =
      10, mean age 51 yrs). Neurovascular tests included axon reflex responses measured
      by laser Doppler velocimeter evoked on the dorsum of the finger by iontophoresis
      of acetylcholine 16 mC in a circumferential chamber: cutaneous microvascular
      dilator responses to endothelial stimulation by iontophoretic application of the
      muscarinic agonist pilocarpine 16 mC and to direct nitrodilator sodium
      nitroprusside 16 mC. The skin temperature of the digits was held between 33
      degrees and 34 degrees C during testing and dilator responses were measured as
      flux change by on-line computer analysis using 'Perisoft'. There was a
      significant reduction (P < 0.05) in the neurovascular responses of both diabetics
      and vibration--exposed subjects to acetylcholine and, in the case of vibration
      exposed subjects, to pilocarpine, but nitroprusside responses were not
      significantly different. Our findings of reductions in neurovascular responses in
      diabetics and in subjects exposed to higher frequency vibration is consistent
      with recent epidemiological findings. Furthermore, subjects treated with an ACE
      inhibitor (enalapril) showed significant reduction in acetylcholine-evoked axon
      reflex responses, while the test group of smokers showed a significant reduction
      in their dilator response to pilocarpine.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1343859
TI  - Frontal signs following subcortical infarction.
AB  - Subcortical cerebral infarction is associated with impaired performance on tests
      of cognitive function which are sensitive to frontal lobe damage. In a cohort of
      82 patients with multiple subcortical cerebral infarcts diagnosed on the basis of
      CT scan appearances, physical signs presumed to be sensitive to frontal lobe
      dysfunction were elicited. Associations between physical findings and CT scan
      changes were determined. The snout reflex was present in 38 patients and
      correlated significantly with the number of lesions, the presence of
      periventricular lucency and the presence of ventricular enlargement, while the
      grasp reflex occurred in 33 and correlated with the number of lesions and the
      presence of ventricular enlargement, and gait impairment in 54 correlated with
      the number of lesions and the presence of ventricular enlargement. It is assumed
      that multiple subcortical infarcts disrupt frontal association pathways,
      resulting in frontal disconnection which produces frontal cognitive dysfunction
      and frontal release signs.

PMID- 1343860
TI  - The molecular genetics of mitochondrial cytopathies: the Melbourne experience.
AB  - Mitochondrial DNA is a unique, maternally inherited molecule encoding several
      subunits of the respiratory enzyme chain. In several mitochondrial cytopathies
      mutations have been described in this genome viz. large-scale heteroplasmic
      deletions in syndromes with progressive external ophthalmoplegia and point
      mutations in MELAS and MERRF encephalomyopathies. We here report Southern blot
      analyses in the cases of CPEO we have seen and describe the search for point
      mutations in MELAS and MERRF. Mitochondrial genetic sequencing in normal and
      disease controls as well as in patients has confirmed the pathogenic nature of a
      tRNA Lys point mutation in MERRF. We propose a novel mitochondrial structural
      gene mutation in a MELAS--like encephalomyopathy: an A-->G substitution at
      position 11084 leading to a Thr to Ala replacement in the ND4 subunit of complex
      I.

PMID- 1343861
TI  - Anti-ganglioside antibodies in peripheral neuropathy.
AB  - There have recently been reports that patients with motor neuropathy with
      multifocal conduction block have high circulating levels of antibodies to the
      ganglioside GM1. Other reports have described the presence of these antibodies in
      patients with inflammatory demyelinating neuropathy and patients with lower motor
      neurone forms of motor neurone disease. We have established an ELISA assay for
      IgG and IgM antibodies to asialo-GM1 (Sigma). We used this assay to measure such
      antibodies in serum from normal subjects and from patients with various
      neurological conditions. In normal subjects, antibodies to asialo-GM1 were
      present only in low levels. An arbitrary scale with an upper limit of normal was
      established. Initial studies have found that abnormally high levels of IgG
      antibodies to asialo-GM1 were present in 4 of 9 patients with inflammatory
      demyelinating neuropathies (Guillain-Barre syndrome or chronic inflammatory
      demyelinating polyradiculoneuropathy). We found one patient with a monoclonal IgM
      circulating paraprotein and a motor neuropathy who had a high titre of antibody
      to asialo-GM1. As yet we have found no patients with motor neurone disease with
      antibodies to asialo-GM1.

PMID- 1343862
TI  - Hereditary sensory radicular neuropathy: defective neurogenic inflammation.
AB  - Hereditary sensory radicular neuropathy exhibits autosomal dominant inheritance
      with complete penetrance in males and incomplete penetrance in females. Newer
      tests of small sensory nerve function were used in screening 8 family members
      aged between 14 and 66 years. All exhibited some frequent features of the
      disorder with an onset in the 2nd or 3rd decade, foot ulceration, foot callus,
      loss of pin prick, thermal and light touch sensation, and some reduction in
      vibration acuity and proprioception in the lower limbs. The hands were involved
      in 3 of 8, muscle involvement was present in 5 of 8, but deafness was not
      detected by audiometry. Nerve conduction velocity, sensory action potentials,
      latency and amplitude, thermal acuity, vibration acuity and axon reflex flares
      were measured in all patients. One sural nerve biopsy confirmed the presence of
      peripheral fibre loss in this predominantly sensory neuropathy. Chemically evoked
      axon reflex tests were used to evaluate the extent of primary sensory nerve fibre
      involvement. All patients were tested using a Moor MBF 3-D dual channel laser
      Doppler velocimeter. Acetylcholine or phenylephrine iontophoretically applied as
      16 mC doses evoked absent or tiny axon reflexes in areas of impaired pin prick
      sensation. By contrast, direct microvascular dilator responses to nitroprusside
      (smooth muscle dependent) and acetylcholine (endothelium-dependent) were present
      but somewhat reduced in areas with defective neurogenic inflammation. These
      results differ significantly from the responses obtained in age-matched healthy
      controls (P < 0.05). Foot pressure analysis was performed for orthoses in 2
      affected members with foot ulceration using the Musgrave Footprint
      system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343863
TI  - Reflex sympathetic dystrophy: altered axon reflex and autonomic responses
      [corrected].

PMID- 1343864
TI  - Enigmatic trigeminal sensory neuropathy diagnosed by facial skin biopsy.
AB  - Facial paraesthesia due to perineural malignant infiltration is a well recognised
      complication of basal and squamous cell carcinomas of the head and neck.
      Perineural involvement was originally attributed to involvement of the perineural
      lymphatics; however subsequent studies have demonstrated conclusively that these
      lymphatics do not exist and that the invasion occurs along the line of least
      resistance. Previous studies on perineural spread of carcinomas of the head and
      neck have emphasised diagnostic biopsy of an involved nerve (e.g. the
      infraorbital, mental or major branches of the trigeminal nerve), or at times
      craniectomy with exploration of the gasserian ganglion. We suggest that in many
      cases the diagnosis can be obtained by biopsy of the anaesthetic skin alone,
      without recourse to more involved biopsy techniques. The following case report
      illustrates this point.

PMID- 1343865
TI  - Late radiation associated neurological injury.
AB  - Late radiation-associated neurological injury is a recognised and often fatal
      complication of therapeutic ionising radiation. This retrospective study outlines
      its highly variable presentation, radiological findings and prognosis over a 6
      year period in a major teaching hospital.

PMID- 1343866
TI  - Postinfectious myelitis, encephalitis and encephalomyelitis.
AB  - Six cases of post-infectious encephalomyelitis are described. A preceding non
      specific viral-like illness occurred 4 to 20 days before the onset of the
      neurological deficits. The clinical syndromes included transverse myelitis, focal
      encephalitis and encephalomyelitis (each in one case) and diffuse encephalitis in
      3. Magnetic resonance imaging appeared to be the investigation of choice. High
      dose corticosteroids were given to 4 patients who recovered partially or fully.
      The patient with focal encephalitis had a spontaneous and complete recovery. The
      remaining patient with diffuse encephalitis died 3 days after the onset; autopsy
      showed prominent lymphocytic perivascular cuffing in the white matter and
      lymphocytic infiltration of the meninges.

PMID- 1343867
TI  - XIXth century pre-Jacksonian concepts of epileptogenesis.
AB  - By the beginning of the XIXth Century the old belief that epilepsy was due to
      demonic possession or to malevolent influences emanating from a variety of
      sources had largely given way to an acceptance that the disorder was a physical
      illness which arose in the brain, though in some not very precisely defined way.
      No even reasonably satisfactory hypotheses about epileptogenesis were available
      till Marshall Hall (1790-1857), from 1836 onwards, popularised the concept of
      reflex action which had earlier been described by Robert Whytt (1714-1776) under
      the name 'sympathy'. Marshall Hall interpreted epilepsy as due to abnormal
      irritability in the afferent limb or central section of what later came to be
      called the reflex arc, loss of consciousness in the seizures being the result of
      secondary cerebral venous congestion. This concept of epileptogenesis was refined
      by Brown-Sequard, who in 1858 ascribed a more important role to overt or occult
      peripheral afferent nerve irritability, considered that the central element of
      the relevant reflex mechanism involved the medulla oblongata, and believed that
      reflex cerebral vasospasm, rather than cerebral venous congestion, caused loss of
      consciousness in the seizures. Almost contemporaneously, Schroeder van der Kolk
      placed considerably greater emphasis on the medullary element in causing the
      increased excitability of the reflex arc that produced epileptic seizures. These
      ideas of exaggerated reflex activity as the mechanism of epilepsy were made
      redundant by the work of Hughlings Jackson (1837-1911), who from 1860 onwards
      demonstrated that epilepsy arose in the cerebrum itself, rather than from altered
      function at lower levels of the nervous system.

PMID- 1343868
TI  - The cervical spine in fatal motor vehicle accidents.
AB  - Of 100 fatal accident cases involving motor vehicles, 60 showed damage to the
      cervical spine, involving bony or disc damage in 31 and focal haemorrhages in
      another 29. In 8 cases, pre-autopsy radiology failed to detect lesions which were
      found by radiology and pathological examination of the post-autopsy specimen.
      Most of the lesions missed were at the C6-7 region. In some cases, the initial
      pathological examination 'missed' laterally placed fractures and small chip
      fractures. Narrow cervical canals in the elderly indicated advanced spondylosis.

PMID- 1343869
TI  - Low osmolar and non-ionic X-ray contrast media and cortical blindness.
AB  - Six cases of contrast neurotoxicity with cerebral visual disturbance following
      angiography are presented. The typical clinical features, putative mechanisms and
      usual outcome of this uncommon but distinctive syndrome are discussed.

PMID- 1343870
TI  - Effect of ritanserin, a highly selective 5-HT2 receptor antagonist, on
      Parkinson's disease.
AB  - There is both experimental and clinical evidence to suggest a role for 5
      hydroxytryptamine (5-HT) in Parkinson's disease. The effect of ritanserin, a
      highly selective 5-HT2 receptor antagonist, on Parkinsonian symptomatology was
      investigated in 10 patients in a single-blind placebo-controlled study. Akinesia
      and gait improved significantly in a dose-dependent manner in 5 and 7 patients
      respectively. However there was no significant improvement in tremor. The effects
      of ritanserin on akinesia and gait are consistent with a role for 5-HT in
      Parkinson's disease.

PMID- 1343871
TI  - Update on surgical treatment of the epilepsies.

PMID- 1343872
TI  - Psychosocial aspects of epilepsy and of epilepsy surgery.

PMID- 1343873
TI  - The influence of other anticonvulsants on the plasma concentration of E-2-en
      valproate.
AB  - E-2-en-valproate is a major metabolite present in the blood of humans treated
      with valproate. In animals it is a potent anticonvulsant. We have measured
      concentrations of valproate and E-2-en-valproate in 102 plasma samples obtained
      from 75 adult patients (20 taking valproate only; 55 taking valproate and other
      anticonvulsants) under steady-state conditions. The two groups' mean ages and
      weights were comparable. The average valproate daily dose was lower (p < 0.002)
      in the monotherapy group (1152 +/- S.D. 661 mg/d) than in the polypharmacy group
      (1902 +/- S.D. 874 mg/d). Despite this, the mean plasma levels of valproate and E
      2-en-valproate were significantly higher (p < 0.05, p < 0.0001, respectively) in
      the monotherapy group (60.0 +/- S.D. 22.6 micrograms/ml; 3.00 +/- S.D. 1.40
      micrograms/ml, respectively) than in the polypharmacy group (49.5 +/- S.D. 24.8
      micrograms/ml; 1.73 +/- S.D. 0.95 microgram/ml). While the mean plasma valproate
      level was 17.5% lower in the polypharmacy group, the mean plasma E-2-en-valproate
      level was 42% lower. The co-administration of other anticonvulsants significantly
      reduced the concentration of valproate and, more so, of E-2-en-valproate in
      plasma.

PMID- 1343874
TI  - Video-audio/EEG monitoring in epilepsy--the Queen Elizabeth Hospital experience.
AB  - Our experience of using video-audio/EEG monitoring in the diagnosis and
      management of epilepsy at The Queen Elizabeth Hospital Comprehensive Epilepsy
      Service from March 1987 to December 1990 is described. We performed 75 long term
      monitoring studies on a total of 66 patients. Following monitoring, a change in
      seizure diagnosis was made in 21 of 66 patients (32%). Pseudoseizures were
      diagnosed in 17 patients. A change in management as a consequence of monitoring
      occurred in 53 of the 66 patients (80%). The referring neurologists considered
      that 56 of the 75 studies (75%) were successful. The investigational technique is
      effective and is particularly useful for the diagnosis of pseudoseizures.

PMID- 1343875
TI  - Salivary concentrations of antiepileptic drugs, oestradiol and progesterone
      throughout pregnancy in epileptic women.
AB  - Epileptic women may experience an increase in seizure frequency during pregnancy.
      To explore the relationship between seizures, simultaneous antiepileptic drug and
      sex hormone concentrations, 8 pregnant epileptic women collected saliva each week
      throughout their pregnancies and for up to 6 weeks after delivery. The ratio of
      the drug dose to the drug's body fluid concentration at steady state (dose:Css),
      as measured by high performance liquid chromatography (HPLC), increased
      throughout pregnancy and fell in the 3rd to 4th week postpartum. There was no
      correlation between the dose:Css ratio and the salivary oestradiol concentration,
      nor between the number of seizures and the antiepileptic drug or sex hormone
      concentrations, and there was only a weak positive correlation between the
      dose:Css ratio and the salivary progesterone concentration. The possible
      interactions between sex hormone concentrations, antiepileptic drug
      concentrations and seizures are complex, and warrant further study in a greater
      number of pregnant subjects.

PMID- 1343876
TI  - Automatisms--the current legal position related to clinical practice and
      medicolegal interpretation.
AB  - The interface between medicine and the law is an area which demands further
      investigation. There can be no criminal capability for an act unless the
      perpetrator had both the will to so act and the capacity to differentiate and
      choose whether or not to conform the particular behaviour to that dictated by the
      law. The capacity for choice must remain the fundamental issue. The range of
      conditions which can raise volition as a defence include: Somnambulism; post
      traumatic syndromes; epilepsy; arteriosclerosis; or acts secondary to cerebral
      neoplasia. There is need to differentiate between reflex actions and automatisms
      and it is imperative that terms such as automatism or automatic behaviour are not
      perverted to allow an excuse for that which is inexcusable. Cases such as that of
      Cogdon, who was acquitted of murdering her daughter; Ramsbottom who was found
      guilty of causing a traffic accident despite having a stroke; Dennison in which a
      driver was found guilty despite epilepsy or Jenkins where the driver was
      initially found innocent of dangerous driving because of the unpredictable nature
      of diabetes are discussed. Special attention will be focused upon the case of
      Sullivan, a landmark in consideration of automatism in epilepsy. The paper
      examines insane verses non-insane automatism and the Australian legal system as
      it affects modern neurological practice. Suggestions are proffered as to how the
      law should be modified to better reflect justice as required within the context
      of modern medical knowledge. 'The social and psychological pressures that shape
      our criminals also shape-those who make and remake the laws which aim to control,
      punish or rehabilitate them, and those who try to change their behaviour.'

PMID- 1343877
TI  - Video EEG analysis of non-ictal events in children.
AB  - Over a 3 year period 186 children aged 3 weeks to 17 years were studied by
      telemetry (prolonged video and EEG monitoring) at the Prince of Wales Children's
      Hospital: 74 had events considered at referral to possibly represent seizures but
      which were shown by clinical analysis and telemetry to be non-ictal. Nine such
      patients were developmentally delayed, one was neurologically impaired and 16
      were both developmentally delayed and neurologically impaired. A specific
      diagnosis of the non-ictal events was reached in 24 subjects-postures of
      spasticity in children with neurological impairment (6), Munchausen-by-proxy (5),
      pseudoseizures (3), breathholding (2), masturbation (2), reflux (2), shudder (1),
      movement disorder (1), motor tic (1) and pertussis (1). Specific descriptive
      patterns were assigned to the remaining 51 events. These included staring (20)
      and jerks (16) or unusual behaviour (15). 49 inter-event EEGs were normal; 7
      displayed abnormal background rhythms and 19 showed epileptiform activity. We
      discourage use of the term 'pseudoseizure' for the majority of the events
      described and prefer that a specific diagnosis be made or a descriptive analysis
      be provided. The events seen illustrate the wide spectrum of childhood behaviour
      and on occasions suggest the need for telemetry to determine their true nature.

PMID- 1343878
TI  - P300 event-related potentials correlated with cerebral blood flow in nondemented
      patients with lacunar infarction.
AB  - We have studied the relationship between the P300 latency and regional cerebral
      blood flow (rCBF) in 25 nondemented patients who had lacunar infarctions in the
      territory of the deep perforating branches of the internal carotid artery system.
      A significant prolongation of the P300 latency with advancing age was observed.
      There was a negative correlation between the P300 latency and the rCBF. These
      results indicate that a combination of P300 latency and rCBF measurements might
      prove more sensitive in detecting mental decline than rCBF studies alone in
      nondemented patients with lacunar infarctions.

PMID- 1343879
TI  - Brazilian contributions to epidemiological aspects of schistosomiasis mansoni.
AB  - A review of epidemiological aspects of endemic areas for schistosomiasis,
      especially in Brazil, will be presented. These studies, performed by several
      authors from different states of the country, have been very useful in indicating
      the relative efficacy of control measures. For example quoting only one aspect,
      specific treatment was demonstrated by Brazilian researchers to be the most
      important individual tool for morbidity control. More recently the study of risk
      factors in endemic areas has been seen to be a very important approach when
      transmission control is the final goal.

PMID- 1343880
TI  - T cell derived cytokines in lung-phase immunity to Schistosoma mansoni.
AB  - In C57Bl/6 strain mice vaccinated with radiation-attenuated cercariae of
      Schistosoma mansoni immune elimination of challenge parasites occurs in the
      lungs. Leucocytes were recovered from the lungs of such mice by bronchoalveolar
      lavage and cultured in vitro with larval antigen; the profile of cytokines
      released was then analyzed. From 14 days after vaccination, BAL cultures
      contained infiltrating lymphocytes which produced abundant quantities of IFN-g
      and IL-3. Challenge of vaccinated mice resulted in a second influx of IFN-g and
      IL-3--producing cells, earlier than after vaccination or in the appropriate
      controls. Ablation studies revealed that CD4+ T cells were the source of IFN-g.
      The timing of cytokine production after vaccination, and challenge was coincident
      with the phases of macrophage activation previously reported. At no time could
      lymphocytes in BAL cultures be stimulated to proliferate with either larval Ag or
      mitogen, in contrast to splenocytes from the same mice. Furthermore, T cell
      growth factor activity was not detected in BAL cultures stimulated with Ag. We
      suggest that the lymphocytes recruited to the lungs are memory/effector cells.
      When Ag released from challenge schistosomula is presented to these cells, they
      respond by secreting cytokines which mediate the formation of cellular aggregates
      around the parasites, blocking their onward migration.

PMID- 1343881
TI  - Molecular and cellular basis of hepatic fibrogenesis in experimental
      schistosomiasis mansoni infection.
AB  - Morbidity in schistosomiasis mansoni occurs primarily as a result of the
      complications of hepatic fibrosis. Yet, the pathogenesis of schistosomal hepatic
      fibrosis is poorly understood. The fact that the hepatic egg granuloma is the
      hallmark of this infection suggests a potential role for granulomatous
      inflammation in hepatic fibrogenesis. Our studies in a murine schistosomiasis
      model indicate that hepatic granuloma cells secrete a variety of fibrogenic
      cytokines that may initiate the scarring process. Among these cytokines, we
      identified a novel protein that we designated fibroblast stimulating factor-1
      (FsF-1). FsF-1 is a lymphokine that can stimulate fibroblast growth and matrix
      synthesis. A notable feature of hepatic fibrosis in this model is that production
      of FsF-1 and other granuloma-derived fibrogenic cytokines is down-regulated in
      chronic infection, an event that may be under immunological control. The
      spontaneous reduction of FsF-1 secretion presumably accounts for reduced scar
      formation late in infection of mice. In the context of relevant clinical studies,
      our findings engender the hypothesis that Symmer's fibrosis may develop in a
      small subpopulation of individuals as a result of immunogenetically-determined
      dysregulation of fibrogenic cytokine production.

PMID- 1343882
TI  - Serum laminin in hepatosplenic human schistosomiasis.
AB  - Serum laminin level was measured in chronic hepatic schistosomiasis. A
      significant increase in the mean serum laminin levels was observed in patients
      with hepatosplenic (HS) schistosomiasis (2.57 +/- 0.83 U/ml), as compared to
      those in patients with the hepatointestinal (HI) form of the disease (1.38 +/-
      0.45-U/ml) and in the control group (1.15 +/- 0.31 U/ml). In the HS patients
      there was a significant direct relation between serum laminin and percutaneous
      splenic pulp pressure (r = 0.68). These findings are compatible with an increased
      production of laminin in hepatosplenic schistosomiasis with may be related to the
      observed enlarged liver and spleen basement membranes in such disease.

PMID- 1343883
TI  - Morphological features of collagen degradation in advanced hepatic
      schistosomiasis of man.
AB  - Optical and electron microscopical evidences of focal matrix degradation were
      frequently seen in liver sections taken from patients with periportal ("pipe
      stem") fibrosis caused by schistosomiasis mansoni. Besides the presence of focal
      areas of rarefaction, fragmentation and dispersion of collagen fibers, the
      enlarged portal spaces also showed hyperplasia of elastic tissue and disarray of
      smooth muscle fibers following the destruction of portal vein branches.
      Ultrastructural changes represented by focal lytic and/or electron dense
      alterations of collagen fibrils were similar to those first seen in experimental
      material and designated as "chronic collagen degradation". Elastin and related
      microfibrils were also affected by focal condensation, fragmentation, distortion
      and dissolution. Schistosome eggs were scanty in the tissue sections examined.
      Matrix degradation represented involuting changes related to the progressive
      diminution of parasite aggression, which occurs spontaneously with age or after
      cure by chemotherapy. Changes of focal matrix degradation now being described
      represent the basic morphological counterpart of periportal fibrosis involution
      documented clinically, especially by ultrasonography, in patients with
      hepatosplenic schistosomiasis submitted to curative chemotherapy.

PMID- 1343884
TI  - Immunological profiles of patients from endemic areas infected with Schistosoma
      mansoni.
AB  - Crude extracts of eggs (SEA) adult worms (SWAP) or cercariae (Cerc) have been
      used to stimulate Peripheral Blood Mononuclear cells (PBMC) and have provided
      rather distinct profiles of responses in different types of patients. In general
      it is clear that patients with early infections respond strongly to SEA while
      response to SWAP are develop more slowly. As infection progresses into the more
      chronic phases, a general pattern is seen which leads to lower anti-SEA
      proliferative responses in the face of higher responses to SWAP and variable anti
      cerc responsiveness. Cured not re-exposed patients express very high levels of
      anti-SEA proliferation. It has recently been seen that those individuals who live
      in endemic areas and have continued water contact, but are repeatedly stool
      negative (who are presumed to have self-cured or be putatively resistant; endemic
      normals) are strongly responsive to antigenic extracts, particularly to SEA.
      Furthermore, our results show that endemic normal individuals have significantly
      higher IFN gamma production upon PBMC stimulation with schistosome antigens than
      infected individuals. With the emergence of more studies it is becoming apparent
      that both the intensity and the prevalence of a given area may influence or shape
      the general responsiveness of the population under study.

PMID- 1343885
TI  - The value of ultrasonography in assessment of portal hypertension in
      hepatosplenic schistosomiasis.
AB  - Ultrasonography can reveal most of the manifestations of portal hypertension
      complicating hepatosplenic schistosomiasis. However, direct demonstration of
      gastroesophageal varices by ultrasonography is still very difficult. An attempt
      was done to correlate sonographic features of portal hypertension with the degree
      of fibrosis to screen patients having varices and predicting their chance of
      bleeding. The results obtained were found to be consistent with the
      esophagogastric endoscopy and with history of hematemesis. Four parameters were
      used, size of spleen, degree of periportal fibrosis, presence of collaterals and
      portal vein diameter. A pilot field survey was also done adopting the same
      principle.

PMID- 1343886
TI  - Duplex hemodynamic evaluation of hepatosplenic mansoni schistosomiasis.
AB  - Conventional ultrasonography highly contributes to a non invasive diagnosis of HS
      schistosomiasis (Cerri et al., 1984). The introduction of Doppler allowed new
      advances in the knowledge of the portal dynamics of this disease (Taylor et al.
      1985; Moriyasu et al., 1986). The aim of this paper was to analyze the
      hemodynamic behavior of the portal vessels, considering caliper, maximum flow
      speed, direction of flow and preferential disposition of the collateral vessels.
      Thirty two patients with schistosomiasis mansoni with confirmed hepatosplenic
      form (HSSM), were analyzed. Fourteen patients with the intestinal form, have been
      analyzed as a control group. The results demonstrated that the maximum speed of
      the portal vein in the two groups has not been significantly different.
      Nevertheless, the diameter of the PV in the hepatosplenic group has been larger.
      The splenic vein presented speed and caliper larger than the superior mesenteric
      vein. The hepatic artery has been detected in only 40% of the cases. The hepatic
      veins presented normal caliper and spectral pattern. The duplex proved to be an
      useful technic complementary and non-invasive, in the study of HSSM.

PMID- 1343887
TI  - Schistosomiasis research funding: the TDR (Special Programme for Research and
      Training in Tropical Diseases) contribution.
AB  - In spite of the recent decline in financial support on the part of some major
      donors, the overall international support for schistosomiasis research in current
      US dollars has been holding steady. However, when adjusted for inflation, a clear
      decline-during the last decade appears and only in a few countries has this
      decline been balanced by increased national or bilateral funding. The prevailing
      level of support for schistosomiasis research is barely sufficient to maintain
      established laboratories and researchers, and highlights the need to attract
      young investigators. The important goal of bringing a new generation of
      scientists into the field of schistosomiasis can only be achieved by a
      considerable long-term increase in funding, both at the national and the
      international levels. A break-through in current research emphasizing improved
      techniques for control is needed to encourage donors and governments to improve
      the situation.

PMID- 1343888
TI  - New approaches to social and economic research on schistosomiasis in TDR (Special
      Programme for Research and Training in Tropical Diseases).
AB  - This paper describes new approaches to social and economic research being
      developed by the Social and Economic Research component of the Special Programme
      for Research and Training in Tropical Diseases of the World Health Organization.
      One of these is a study to assess the possibility of identifying high risk
      communities for urinary schistosomiasis through a "mailed" questionnaire approach
      distributed through an existing administrative system, thereby eliminating the
      need for face-to-face interviews by the research or disease control team. This
      approach, developed by the Swiss Tropical Institute in Ifakara, Tanzania, is
      currently being tested in seven other African countries. The paper also describes
      a change of emphasis of economic research on schistosomiasis, focusing on the
      intra-household effects of the disease on rural households, rather than, as
      previously done, studying the impact of the disease on the productivity of
      individual wage labourers. Other priorities involve the identification of
      epidemiological information needed for improved decision-making regarding
      acceptable treatment strategies in endemic areas with limited financial capacity,
      as well as research on how the adverse effects of economic development projects
      can be alleviated.

PMID- 1343889
TI  - Effector functions of eosinophils in schistosomiasis.
AB  - The dual function of eosinophils is clearly illustrated in schistosomiasis. Well
      equipped in membrane receptors for immunoglobulins and complement, and due to the
      presence of granule basic proteins, eosinophils can become cytotoxic for parasite
      larvae and thus participate to protective immunity. However, mediators can also
      exert their cytolytic effect on normal cells or tissues, inducing therefore
      pathology. through ADCC mechanisms against schistosome larvae in vitro involving
      different antibody isotypes (IgG, IgE and IgA) and also in experiments performed
      in vivo, eosinophils have been clearly involved in protective immunity. Although
      no direct evidence of the protective role of eosinophils were brought in humans,
      the striking association of eosinophil-dependent cytotoxic antibody isotypes with
      resistance to reinfection (for instance IgE and IgA antibodies), whereas in vitro
      blocking antibody isotypes (IgG4, IgM) were detected in susceptible subjects,
      strongly, suggested the participation of eosinophils in antibody-dependent
      protective immune response. However eosinophils could also participate to
      granuloma formation around S. mansoni eggs and consequently to the pathological
      reactions induced by schistosomiasis.

PMID- 1343890
TI  - Experimental murine schistosomiasis mansoni: establishment of the chronic phase
      of the disease.
AB  - After the acute hyperergic phase of schistosomal infection, the chronic phase of
      the disease corresponds to the establishment of a relative equilibrium between
      the host and the parasite. This involves: (1) A shift from the predominance of
      the TH2 response observed in the acute phase, to the predominance of the TH1
      response in the chronic phase of the disease, with modification of lymphokine and
      immunoglobulin secretions patterns. (2) Redistribution of hosts responses to
      parasite, with predominance of systemic controls in the acute phase, and a shift
      towards local tissue responses in the chronic phase. This redistribution relieves
      the hyperergic response involving the whole body of the host, and delimits
      cellular and molecular reactions to parasites to only those tissues that are
      directly involved by the adult parasites and their eggs. Mobilization of
      eosinophil granulocytes in schistosomal periovular granulomas is one of examples
      of this redistribution.

PMID- 1343891
TI  - Cross-sectional and evolutive studies of schistosomiasis mansoni in untreated and
      mass treated endemic areas in the southeast and northeast of Brazil.
AB  - Cross-sectional and evolutive studies on schistosomiasis mansoni were carried out
      before and after mass treatment in the endemic areas of Capitao Andrade and Padre
      Paraiso, state of Minas Gerais, Riachuelo, state of Sergipe, Alhandra, state of
      Paraiba, and Alianca, Alegre and Coroata, lowland of the state of Maranhao,
      Brazil, in the last eighteen years. The studies included clinical and fecal
      examination by the Kato-Katz quantitative technique, skin test for Schistosoma
      mansoni infection, evaluation of man-water contact and other epidemiological
      investigations such as infection rate and dynamic of the snail population.
      Results showed: (1) Higher prevalence of S. mansoni infection, greater egg load
      elimination and higher and earlier morbidity of the chronic forms of the disease
      in the southeast areas of Capitao Andrade and Padre Paraiso; (2) The incidence of
      hepatosplenic form is higher in some family clusters, in whites and mulattos in
      all the endemic areas but develop earlier in the southeast; (3) The prevalence
      and morbidity of schistosomiasis are decreasing both in the mass treated
      northeast and in the untreated southeast areas; (4) The mass treatment reduces
      rapidly the prevalence of the infection and the morbidity of the disease but can
      not control it because of the frequent reinfections due to the intensity of man
      water contact.

PMID- 1343892
TI  - Portal hypertension in schistosomiasis: pathophysiology and treatment.
AB  - In heavily infected young patients, there is a "non-congestive" phase of the
      disease with splenomegaly which can improve after chemotherapy. A strong
      correlation between hepatosplenic form and worm burden in young patients has been
      repeatedly shown. The pattern of vascular intrahepatic lesions, seems to depend
      on two mechanisms: (a) egg embolization, with a partial blocking of the portal
      vasculature; (b) the appearance of small portal collaterals along the
      intrahepatic portal system. The role played by hepatitis B virus (HBV) and C
      virus infections in the pathogenesis of liver lesions is variably considered.
      Selective arteriography shows a reduced diameter of hepatic artery with thin and
      arched branches outlining vascular gaps. A rich arterial network, as described in
      autopsy cases, is usually not seen in vivo, except after splenectomy or shunt
      surgery. An augmented hepatic arterial flow was demonstrated in infected animals.
      These facts suggest that the poor intrahepatic arterial vascularization
      demonstrated by selective arteriography in humans is due to a "functional
      deviation" of arterial blood to the splenic territory. The best results obtained
      in treatment of portal hypertension were: esophagogastric devascularization and
      splenectomy (EGDS), although risk of rebleeding persists; classical (proximal)
      splenorenal shunt (SRS) should be abandoned; distal splenorenal shunt may
      complicate with hepatic encephalopathy, although later and in a lower percentage
      than in SRS. Propranolol is currently under investigation. In our Department,
      schistosomatic patients with esophageal varices bleeding are treated by EGDS and,
      if rebleeding occurs, by sclerosis of the varices.

PMID- 1343893
TI  - Experiences with the control of schistosomiasis mansoni in two foci in central
      Africa.
AB  - Experiences with population-based chemotherapy and other methods for the control
      of schistosomiasis mansoni in two subsaharan foci are described. In the forest
      area of Maniema (Zaire), intense transmission of Schistosoma mansoni, high
      prevalences and intensities of infection, and important morbidity have been
      documented. Taking into account the limited financial means and the poor logistic
      conditions, the control strategy has been based mainly on targeted chemotherapy
      of heavily infected people (> 600 epg). After ten years of intervention,
      prevalences and intensities have hardly been affected, but the initial severe
      hepatosplenic morbidity has almost disappeared. In Burundi, a national research
      and control programme has been initiated in 1982. Prevalences, intensities and
      morbidity were moderate, transmission was focal and erratic in time and space. A
      more structural control strategy was developed, based on screening and selective
      therapy, health education, sanitation and domestic water supply. Prevalences and
      intensities have been considerably reduced, though the results show focal and
      unpredictable variations. Transmission and reinfection were not significantly
      affected by chemotherapy alone, and the eventual outcome of repeated selective
      treatment appears to be limited by the sensitivity of the screening method.
      Intestinal morbidity was strongly reduced by community-based selective treatment,
      but hepatosplenic enlargement was hardly affected; this is possibly due to the
      confounding impact of increasing malaria morbidity. The experiences show the
      importance of local structures and conditions for the development of an adapted
      control strategy. It is further concluded that population-based chemotherapy is a
      highly valid tool for the rapid control of morbidity, but should in most
      operational conditions not be considered as a tool for transmission
      control.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343894
TI  - Vaccine strategies against schistosomiasis.
AB  - In this review the authors analyze the effector and regulatory mechanisms in the
      immune response to schistosomiasis. To study these mechanisms two animal models
      were used, mouse and rat. The mouse totally permissive host like human, show
      prominent-T cell control in the acquisition of resistance. But other mechanisms
      like antibody mediated cytotoxicity (ADCC) involving eosinophils and IgG
      antibodies described in humans, are observed in rats. Also in this animal, it is
      observed specific IgE antibody high production and blood and tissue eosinophilia.
      Using the rat model and schistosomula as target, some ADCC features have emerged:
      the cellular population involved are bone marrow derived inflammatory cell
      (mononuclear phagocytes, eosinophils and platelets), interacting with IgE through
      IgE Fc receptors. Immunization has been attempted using the recombinant protein
      Sm28/GST. Protection has been observed in rodents with significant decrease of
      parasite fecundity and egg viability affecting the number, size and volume of
      liver egg granulomas. The association of praziquantel and immunization with
      Sm28/GST increases the resistance to infection and decreases egg viability. The
      authors suggest the possibility of the establishment of a future vaccine against
      Schistosoma mansoni.

PMID- 1343895
TI  - [Specific treatment as a weapon for controlling schistosomiasis].
AB  - The specific treatment of schistosomiasis has been thought to prevent or revert
      severe forms of the disease, since 1957. Starting in 1977, prospective and
      controlled studies performed in different endemic areas of Brazil were able to
      confirm such facts. The new drugs, of high efficacy and well tolerated-
      Oxamniquine and Praziquantel--can actually prevent and cure the severe forms of
      some patients, contributing to change the morbidity pattern of the disease, thus
      being considered as important weapons in its control. Analysis of the principal
      Brazilian articles on the subject is presented.

PMID- 1343896
TI  - Age-targeted chemotherapy for control of urinary schistosomiasis in endemic
      populations.
AB  - Severity of urinary tract morbidity increases with intensity and duration of
      Schistosoma haematobium infection. We assessed the ability of yearly drug therapy
      to control infection intensity and reduce S. haematobium-associated disease in
      children 5-21 years old in an endemic area of Kenya. In year 1, therapy resulted
      in reduced prevalence (66% to 22%, P < 0.001) and intensity of S. haematobium
      infection (20 to 2 eggs/10 mL urine), with corresponding reductions in the
      prevalence of hematuria (52% to 19%, P < 0.001). There was not, however, a
      significant first-year effect on prevalence of urinary tract abnormalities
      detected by ultrasound. Repeat therapy in years 2 and 3 resulted in significant
      regression of hydronephrosis and bladder abnormalities (41% to 6% prevalence, P <
      0.01), and further reductions in proteinuria. Repeat age-targeted therapy was
      associated with decreased prevalence of infection among young children (< 5 yr)
      entering into the targeted age group. Two years after discontinuation of therapy,
      intensity of S. haematobium infection and ultrasound abnormalities remained
      suppressed, but hematuria prevalence began to increase (to 33% in 1989).
      Reinstitution of annual therapy in 1989 and 1990 reversed this trend. We conclude
      that annual oral therapy provides an effective strategy for control of morbidity
      due to S. haematobium on a population basis, both through regression of disease
      in treated individuals, and prevention of infection in untreated subjects.

PMID- 1343897
TI  - Genetic complementation analysis of two independently isolated hycanthone
      resistant strains of Schistosoma mansoni.
AB  - The objective of this study is to determine whether various hycanthone resistant
      strains of schistosomes which have been independently isolated are all affected
      in the same gene. A strain obtained from a Brazilian patient was compared with a
      strain of Puerto Rican origin selected in the laboratory. If the mutation
      conferring resistance involved two different genes, one would expect that progeny
      of a cross between the two strains would show complementation, i.e. it would be
      sensitive to the drug. We have performed such a cross and obtained F1 hybrid
      worms which were essentially all resistant, thus suggesting that the mutation
      conferring resistance in the two strains involves the same gene.

PMID- 1343898
TI  - Alternative approaches in schistosomiasis control.
AB  - Measures for the control of schistosomiasis were implemented in Egypt beginning
      1922. This shows that developing endemic countries are facing this problem for
      near 70 years. However, results in the control of this infection have not been
      satisfactorily obtained in spite of the technologies and strategies recently
      developed. The idea that social and economic components are relevant in the
      control of schistosomiasis is not new although its extension and profundity have
      not usually been well understood. More recently, most of the workers have
      recognized that the focal distribution of the prevalence rates of schistosomiasis
      should not be neglected in the control of the infection. At present, field work
      projects on the control of schistosomiasis are being developed in rural areas of
      two Brazilian studies (Espirito Santo and Pernambuco). The adopted strategy aims
      to interfere in the complex relationships between man and his bio-social-cultural
      environment, without forgetting that the unequal distribution of the space is a
      consequence of the political and economic organization of the Society.

PMID- 1343899
TI  - Some personal views on the control of schistosomiasis mansoni.
AB  - Our views are based, among other, on a recent study of a district of Uniao dos
      Palmares (Alagoas). Although being a very compact community (32 city blocks
      holding two thousand families), transmission is very uneven, the geometric mean
      egg counts in the various blocks ranging between extremes of 96 and 1920.
      (Results do not correlate with the availability of domestic water supply). We
      thus are led to conclude that: (a) transmission is primarily peridomestic,
      resulting from pollution of open ditches and other collections of water; (b)
      control of transmission can be done on a selective basis, requiring quite modest
      investments. Given the inefficacy of population-based chemotherapy, when used
      alone, the author insists that this alternative cannot any longer be overlooked.
      He also regrets the emphasis placed upon vaccine development; allegations that
      this would, at any rate, prevent severe morbidity can be dismissed, since
      whatever the cause-morbidity due to schistosomiasis has been rapidly declining in
      Northeast Brazil.

PMID- 1343900
TI  - New approaches for the control and eradication of schistosomiasis in Venezuela.
AB  - Schistosomiasis in America with the exception of Brazil, behaves as a chronic
      mild disease with few clinical manifestations due to low parasite burden. These
      features restrict the clinical and parasitological diagnosis. The most commonly
      used stool examination method, Kato-Katz, becomes insensitive when the majority
      of individuals excrete less than 100 eggs/g of feces. In view that antigen
      detecting techniques have not been able to reveal light infections, the antibody
      detecting assays remain as a very valuable diagnostic tool for epidemiological
      surveillance. The Venezuelan Schistosomiasis Research Group (CECOICE) has
      designed a mass chemotherapy strategy based on sero-diagnosis. Since blood
      sampling is one of the important limiting factors for large seroepidemiological
      trials we developed a simple capillary technique that successfully overcame most
      of the limitations of blood drawing. In this sense, ELISA seems to be the most
      adequate test for epidemiological studies. Soluble egg Schistosoma mansoni
      antigen (SEA) has been largely used in Venezuela. The sensitivity of ELISA-SEA in
      our hands is 90%, moreover its specificity reach 92% when populations from non
      endemic areas but heavily infected with other intestinal parasites are analyzed.
      The Schistosomiasis Control Program is currently carrying out the surveillance of
      endemic areas using ELISA-SEA as the first screening method, followed by the
      Circumoval Precipitin test for validation assay. The results with these two
      serological techniques allowed us to defined the criteria of chemotherapy in
      populations of the endemic areas. On the search of better diagnostic technique,
      Alkaline Phosphatase Immunoenzyme Assay (APIA) is being evaluated in field
      surveys.

PMID- 1343901
TI  - [Control of schistosomiasis mansoni in an area of low transmission].
AB  - The schistosomiasis is transmitted by Biomphalaria tenagophila in our study area
      (Pedro de Toledo, Sao Paulo, Brazil). From 1980 to 1990 epidemiological surveys
      in a population of 4,000 inhabitants, has shown that: prevalences by Kato-Katz
      (KKT), immunofluorescence (FT) and intradermal (IDT) techniques were 22.8%, 55.5%
      and 51.8%, respectively; intensity of infection was low, 58.5 eggs per gram of
      faeces (epg); there were no symptomatic cases; prevalences were higher in mates,
      children and rural zone; index of potential contamination was 57.5% in the age
      group 5 to 20 years; 2/3 of patients were autochthonous; cases were no-randomly
      aggregated; transmission was focal and only 0.4% of snails were infected; water
      contacts through recreation showed the most important odds ratio; knowledge,
      attitudes and practices were satisfactory. From the epidemiological findings a
      control programme was carried out: yearly faeces exams, chemotherapy,
      molluscocide, health education and sanitation. Thus, the prevalence decreased
      sharply to 3.3% and intensity of infection to 30.3 epg; the incidence rates
      ranged between 0.4% and 2.5% annually; the sanitation became better and the
      youngsters were the main target in prophylaxis. To improve control,
      immunodiagnosis has to be conducted and the involvement of the population should
      be increase. However, we cannot forget that re-infection, therapeutic failure,
      etc, could play a major role in the maintenance this residual prevalence.

PMID- 1343902
TI  - Epidemiological features and control of schistosomiasis japonica in China.
AB  - Achievements and successes have been obtained in schistosomiasis control in
      China. An epidemic survey was carried out and its results analyzed.

PMID- 1343903
TI  - Identification of schistosome-infected snails by detecting schistosomal antigens
      and DNA sequences.
AB  - Cercarial shedding tests do not provide species identification of the
      schistosomes concerned and cannot detect prepatent schistosomal infections. We
      have demonstrated that both immunodetection by ELISA of schistosomal antigens in
      snail hemolymph, and dot hybridization of snail extracts by a DNA probe
      representing highly repeated sequences, proved suitable for detecting infected
      snails during prepatency as well as patency. A group-specific monoclonal antibody
      was found to be suitable for detecting Schistosoma mansoni infection in
      Biomphalaria sp., but not for positive identification of S. haematobium in
      Bulinus sp. Comparative evaluation of the diagnostic qualities, and technical
      aspects and cost of these tests, point to the superiority of the immunodetection
      approach for large scale detection of snails prepatently infected with S.
      mansoni. This approach is potentially useful for providing extended information
      on schistosome-snail epidemiology that may facilitate rapid evaluation of the
      danger of post-control reinfection, and help make decisions on the time and place
      of supplementary control measures. In this context the potential usefulness of
      the immunodetection or DNA probing approach for facilitating catalytic model
      representation of schistosome-snail epidemiology warrants further evaluation.
      Specific identification of S. haematobium in Bulinus by either of these
      approaches may be possible depending on the development of suitable antibodies or
      DNA probes.

PMID- 1343904
TI  - Ecological studies on the intermediate host snails and the relevance to
      schistosomiasis control.
AB  - A detailed knowledge of distribution patterns of schistosome intermediate hosts
      and their population dynamics and factors affecting these patterns will provide
      useful information about the possibilities and desirability of conducting snail
      control measures in various transmission situations. On the basis of various case
      studies the association between the occurrence of human water contacts and the
      presence of schistosome intermediate hosts or infections in the intermediate
      hosts is illustrated. Other parameters affecting snail distribution patterns and
      density fluctuations are discussed. It is concluded that ecological studies on
      the intermediate hosts are extremely relevant, either to optimally apply existing
      control measures or to develop alternative measures of snail control, such as
      ecological or biological control.

PMID- 1343905
TI  - Holochilus brasiliensis and Nectomys squamipes (Rodentia-Cricetidae) natural
      hosts of Schistosoma mansoni.
AB  - After several Brazilian researchers, the author examines the capacity of two
      species of rodents Cricetidae, Holochilus brasiliensis and Nectomys squamipes, to
      maintain the biological cycle of Schistosoma mansoni in the field and to be
      parasite reservoir: (a) the role they are able to play in human endemy; (b) the
      methods necessary to characterize the population of Schistosoma mansoni related
      either to man, either to rodents, either to both.

PMID- 1343906
TI  - Further development of the baboon as a model for acute schistosomiasis.
AB  - Baboons develop a syndrome, including eosinophilia and transient fever, after
      infection with cercariae of Schistosoma mansoni that is consistent with the human
      syndrome of acute schistosomiasis. Radiotelemetry can be used to follow the
      course of fever in infected baboons. Individual variations in intensity of
      disease were noted in baboons. These symptoms and signs were more closely linked
      to the onset of oviposition by the newly matured worms than they were to the
      presence of migrating schistosomula or maturing worms. The baboon is concluded to
      be a suitable and useful model for human acute schistosomiasis mansoni.

PMID- 1343907
TI  - Pre- and post-treatment immunodiagnostic evaluation in human schistosomiasis
      mansoni.
AB  - Schistosomiasis control seems to be different in countries were low parasitic
      burden and asymptomatic clinical patients are the features of majority of cases.
      Immunological methods must substitute the traditional coprologic techniques used
      for some decades in the Control Program. Circumoval Precipitin Test (COPT),
      intradermal test and ELISA with soluble egg antigen (SEA) are evaluated for using
      as tools for seroepidemiologic studies. COPT and ELISA were performed after
      treatment to known their utility when impact of chemotherapy must be assessed.
      One hundred sixty five persons were followed up 3, 6, 9 and 12 months after
      treatment. The mean sensitivity of COPT studied by age groups was 95.6% which is
      very important considering that 88.4% of the studied population excreted less
      than 100 eggs/gr of feces, while sensitivity of intradermal test was 58.2%.
      Children showed the highest reactivity to COPT. When treatment is effective, COPT
      reactivity progressively diminish until become negative one year later. In the
      non cure group, the COPT reactivity diminished but never below 20%. ELISA-SEA did
      not modify one year after treatment. Effort should be made to isolate fractions
      of eggs of Schistosoma mansoni whose antibodies disappear after treatment.

PMID- 1343908
TI  - Mini-review: the ultrasonographical and serological changes and their improvement
      after praziquantel treatment in Schistosoma japonicum infected patients in Leyte,
      Philippines.
AB  - We have identified the specific ultrasonographical (US) changes in Schistosoma
      japonicum infected patients with the serological changes in general liver
      function markers. The US examination with the following haematological and
      biochemical serum analysis was performed on 102 patients in Schistosomiasis
      Hospital, Leyte, Philippines. The US liver images were classified into 4 patterns
      according to the development of periportal fibrosis and the patterns of echogenic
      bands. Among various haematological and biochemical serum parameters of liver
      damage. The serum levels of total bile acid (TBA) and procollagen-III-peptide (P
      III-P) correlated well with the development of hepatic fibrosis and the portal
      hypertension. These patients were subsequently treated with praziquantel (3 x 20
      mg/kg), and the improvement of the thickening of the portal vein wall and the
      intensity of the echogenic band formation was detected 6 months after treatment.
      The significant US changes could not be detected in the patients with severe
      hepatic fibrosis caused in the long term infection. The results revealed that the
      US examination with the serum TBa level would provider a sensitive tool to
      monitor the severity of the infection and also the improvement occurred shortly
      after praziquantel treatment.

PMID- 1343909
TI  - Efficacy of Niclosamide as a potential topical antipenetrant (TAP) against
      cercariae of Schistosoma mansoni in monkeys.
AB  - A 1% (W/V) formulation of Niclosamide (2', 5-Dichloro-4-nitrosalicylanilide)
      (TAP) was tested on Cebus apella monkeys as a topical prophylactic against
      schistosomiasis mansoni. Two experiments were conducted using the same
      formulation. In the first experiment, the TAP provided complete protection
      against schistosomiasis for 3 days. Of the 4 monkeys treated with TAP 7 days
      before exposure to Schistosoma mansoni cercariae, 2 were completely protected.
      The remaining 2 monkeys of the 7 day treatment group had a 78% or greater
      reduction in adult worm burdens when compared to the placebo treated monkeys. The
      second experiment was designed to determine the time between day 3 and 7 when the
      TAP no longer provided complete protection. However, all of the TAP treated
      monkeys in this experiment were completely protected, even the monkeys treated 7
      days earlier. In both experiments, all monkeys used as infection controls and
      those receiving only the placebo became infected and showed typical experimental
      schistosomiasis. These results demonstrate that the TAP could provide fast
      acting, short-term protection to people who must enter cercariae infested water.

PMID- 1343910
TI  - Present aspects of immunodiagnosis of schistosomiasis.
AB  - Facilitated and improved by advances in molecular biology, techniques for the
      immunodiagnosis of schistosomiasis, including assays based on the detection of
      antigens circulating in the serum and/or excreted in the urine, have now reached
      the stage of multi-centre trials. There is a need to complement parasitological
      techniques as some national programmes are becoming increasingly successful in
      establishing control of the disease and the classical approach frequently fails
      to reveal low-intensity infection. Epidemiological survey teams in some areas
      have tentatively started to use serology and their experience indicates that
      antibody detection suffices in eradicated or controlled areas with low expected
      prevalence but that detection of circulating antigens is needed for assessment of
      the incidence of infection or reinfection in areas recently brought under
      control. Before reagents and procedures can be recommended for routine use of
      national control programmes, the assays must be standardized with sera from
      clinically well-characterized patients in geographically defined regions, hence
      emphasizing the need for a reference serum bank. Implementation of serological
      testing, carried out by national public health laboratories using standardized
      testing systems, would permit valid comparisons between different areas providing
      support for decisions regarding national health policies.

PMID- 1343911
TI  - Interrelationship between schistosomiasis and concomitant diseases.
AB  - The biological literature contains many examples of mutual influences between
      different species of parasites, especially with respect to concomitant helminth
      infections. Several situations are known in which the association of infection by
      Schistosoma mansoni with other pathogens in the same host results in a type of
      disease which differs from the simple summation of the individual effects of each
      infection. The present study concerns concomitant infections involving S. mansoni
      and enterobacteriaceae; S. mansoni and other helminths such as Ascaris
      lumbricoides, Ancylostomids, Toxocara canis and species of the genus Hymenolepis;
      S. mansoni and different protozoa such as Trypanosoma cruzi, T. brucei,
      Toxoplasma gondii and Plasmodium berghei. The interaction between hepatitis B
      virus and S. mansoni, leading to prolonged viremia and worsening of liver damage,
      is also discussed. The paper also treats the simultaneous occurrence of
      schistosomiasis and other aggravating factors such as malnutrition and neoplasias
      which may alter the host's response to the trematode.

PMID- 1343912
TI  - Nutrition and acute schistosomiasis.
AB  - In northeast Brazil, nutritional deficiency diseases and schistosomiasis mansoni
      overlap. An experimental model, which reproduces the marasmatic clinical form of
      protein-energy malnutrition, was developed in this laboratory to study these
      interactions. Albino Swiss mice were fed with a food association ingested usually
      by human populations in northeast Brazil. This diet (Regional Basic Diet - RBD)
      has negative effects on the growth, food intake and protein utilization in
      infected mice (acute phase of murine schistosomiasis). Nitrogen balance studies
      have also shown that infection with Schistosoma mansoni has apparently no effect
      on protein intestinal absorption in well nourished mice. However, the lowest
      absorption ratios have been detected among RBD--fed infected animals, suggesting
      that superimposed schistosome infection aggravated the nutritional status of the
      undernourished host. The serum proteins electrophoretic pattern, as far as
      albumins are concerned, is quite similar for non-infected undernourished and
      infected well-fed animals. So, the significance of albumins as a biochemical
      indicator of the nutritional status of human populations residing in endemic foci
      of Manson's schistosomiasis, is discussable.

PMID- 1343913
TI  - Seroepidemiology of schistosomiasis mansoni.
AB  - In population surveys in which the Schistosoma mansoni intensity of infection is
      low, or in localities where the schistosomiasis control program had success, the
      parasitologic methods lack in sensitivity. Despite of some limitations, the
      immunological methods are useful to provide valuable information in such field
      conditions. Thus, the prevalence of schistosomiasis in untreated population can
      be determined by the detection of IgG or IgM antibodies, as well as the incidence
      by the IgA antibodies, employing mainly immunofluorescence (IF) and
      immunoenzymatic (ELISA), and in some extent hemagglutination (HA) or even skin
      test. The true prevalence and incidence of schistosomiasis can be estimated using
      a probabilistic model equation, since knowing before-hand the sensitivity and
      specificity of employed test. The sensitivity and the specificity of serologic
      test become higher in low aged group, under 14. The geometric mean IF titers also
      gives a positive correlation with the intensity of infection. Presently, there
      are need of serologic tests which are economic and practical in seroepidemiologic
      inquiries, requiring no specialized personnel to collect population blood or
      serum samples, and also easily interpret the test results. The reagents for such
      tests are desired to be stable and reproducible. Moreover, it is expected that
      the tests can distinguish an active infection.

PMID- 1343914
TI  - Intermediate hosts of Schistosoma mansoni in Brazil.
AB  - The Brazilian planorbidical chart is slowly but progressively been increased by
      new data. Distribution of vector species of Schistosoma mansoni, according to
      Paraense, 1986, may be thus resumed: Biomphalaria glabrata--delimited by
      parallels 13 and 21 degrees S and meridians 39 and 45 degrees W, area of greater
      dominance (Southeast Bahia, oriental hal of Minas Gerais and Espirito Santo). It
      is observed along the coast line of the states of Sergipe, Alagoas, Pernambuco,
      Paraiba and Rio Grande do Norte. Starting from there, it is found towards the
      southwest, in the direction to the Sao Francisco River and South-Center of Minas
      Gerais. Isolated population may be observed in other states. Its presence is
      probably, associated to the transmission of schistosomiasis in all areas where it
      occurs. B. tenagophila--extends it self through a wide strip of coast-line from
      the South of Bahia (17 degrees 45'S; 39 degrees 15'W), RS (33 degrees 41'S, 53
      degrees 27'W). In Sao Paulo and Rio Grande do Sul states it is found further
      inland. It is important in schistosomiasis transmission in the Paraiba valley
      (SP). Isolated populations are observed in the Federal District and Minas Gerais
      state. B. straminea--better adapter species to climatic variation, having a more
      dense distribution in the northeast (41 degrees W and 110 degrees S), south of
      Bahia and northeast of Minas Gerais (150 and 180 degrees S, 400 and 440 degrees
      W). It is less susceptible than the B. glabrata, being however, the most
      important responsible for the transmission of S. mansoni in the northeast,
      chiefly in the northeastern dry area, where it is almost the only transmissive
      species.

PMID- 1343915
TI  - [Malacologic diagnostic methods].
AB  - Specific identification of the snail vectors: (a) shell features; (b) animal
      features (genital organs); (c) biochemical techniques (electrophoresis). The
      snail infection rates: (a) exposure to light and cercarial identification; (b)
      snail crushing and identification or the larval forms in the tissues.

PMID- 1343916
TI  - [Measures for control of schistosomiasis adopted by the National Health
      Foundation].
AB  - The control measures used by the Ministerio da Saude/Fundacao Nacional de Saude
      for 1990/1991, started to have a new focus when significant advances were
      evidenced in the two last decades and after internal meetings with participation
      of the scientific community interested in accompanying the actions directed to
      the control of schistosomiasis in our country. Since then, the priority started
      to be the suppressing of the occurrence of advanced clinical forms, having as an
      objective, the detection and treatment of all carrier of Schistosoma mansoni.
      Beyond the control measures, factors that may interfere in the application of
      those measures were also studied, the diverse phases of field operations, the
      work methodology and results obtained in the first semester of 1991.

PMID- 1343917
TI  - [Acute or toxemic form of schistosomiasis mansoni].
AB  - The acute or toxemic form of schistosomiasis mansoni is studied under the
      anatomic and clinical point of view, according to classification made by Neves,
      Raso and Bagliolo in 1975. The first phase is characterised by the following
      facts: cutaneous (immediate and late) manifestations; high fever or in
      progressive elevation; intense diaphoresis abdominal discomfort; intense aqueous
      diarrhea; dehydration; loss of weight, dry cough; painful hepatosplenomegaly;
      discreet lymphadenomegaly, progressive increase of blood leucocytes and
      eosinophiles; radiological pulmonary alterations; absence of alterations in serum
      protein and hepatic functional tests; the hepatic function biopsy shows focus of
      acute hepatitis. The second stage or properly named toxemic period was clinically
      characterized by the neat aggravation of the previously observed phenomena. At
      last, the evolutive course of the disease has implication derived not only the
      worm's presence, but from the intense dissemination of eggs in the tissue. In the
      pre-laying phase one studied the forms of cercarian dermatitis, prodromic and
      inapparent. In the post laying phase, the properly named acute toxemic form, with
      its types: pseudocholeraic, pseudotyphous, pseudodysenteric-bacillary,
      pseudonephritic, pseudoenterovirotic, the reactivated, the ischemic enterocolitis
      and others; whenever possible clinical and anatomic correlation will be made.

PMID- 1343918
TI  - Parasitological diagnosis of schistosomiasis mansoni: fecal examination and
      rectal biopsy.
AB  - Even with all progress in the search of sensitive and specific methods for the
      immunological diagnosis of schistosomiasis, the microscopic detection of eggs of
      the parasite in the stool still remains the most widely used tool for the actual
      diagnosis of active infection. Among the coproscopic methods, Kato's technic
      modified by Katz et al (Kato/Katz) has the advantages of higher sensitivity, the
      possibility of egg quantification, its low operational cost and its feasibility
      in areas with minimal infra-structure. The oogram of the rectal mucosa is
      valuable in initial clinical trials of schistosomicides, when it is needed to
      observe egg morphology in tissue. It could be an alternative method for
      individual diagnosis, being more sensitive than a single stool exam in low
      intensity infection. However, the increased sensitivity of a higher number of
      fecal exams makes that invasive procedure unnecessary. In the assessment of cure
      of schistosomiasis, Kato/Katz method (three fecal samples in one, three and six
      months after treatment) and the rectal biopsy four months after treatment, are
      equally reliable.

PMID- 1343919
TI  - [Immunodiagnosis of schistosomiasis mansoni].
AB  - In the last years, the knowledge about immunodiagnosis in schistosomiasis has
      increased considerably. This was due to a better immunologic understanding of the
      host-parasite interaction and the evolution of the technical procedures by the
      introduction of new concepts and techniques. The search of more sensitive,
      specific, practical and less expensive diagnostic tests has led to the
      development of a great number of immunological tests that could complement the
      limitations of the parasitological diagnosis. The antigens of different life
      cycle stages of Schistosoma mansoni may be used as target for immunodiagnostic
      tests and the anti-schistosome antibodies in the sera of infected patients can be
      detected. The research of circulating schistosome antigens, the production of
      specific antisera and the application of these antibodies in immunodiagnostic
      tests have also been discussed.

PMID- 1343920
TI  - Pathogenesis of Schistosoma mansoni infection.
AB  - In this paper a discussion is made on the pathogenesis of schistosomiasis mansoni
      in mice, presented from the perspectives of "processes", "mediators", "strategies
      for study" and "disease". These concepts overlap considerably. Regarding
      "processes", granulomas, fibrosis and vasculitis are discussed. The role of
      mediators, including cells, antibodies and immune complexes, cytokines and distal
      mediators is commented as related to the pathological processes occurring in
      schistosomiasis. Finally, strategies for study are presented, followed by a
      discussion on the etiopathogenesis of the different clinical stages and
      pathologic manifestations of schistosomiasis mansoni.

PMID- 1343921
TI  - [Schistosomiasis mansoni--drug treatment].
AB  - It is the specific treatment of mansoni schistosomiasis that aims to act directed
      on the parasite, through chemotherapy. Constitutes fundamental indication to the
      treatment of schistosomiasis active forms, that is, these determined by the
      presence of living eggs in the feces or in material from rectal biopsy, since
      eventual contra indications are respected. Two are the medicaments actually used:
      oxamniquine, used in the single dosage of 15 mg/kg, V.O. for adults and 20 mg/kg
      V.O. for children divided in two doses, offers a percentage of 30 to 40% of
      cures, evaluated by quantitative "oogram" and praziquantel, in the single dose of
      60 mg/kg V.O., presents a cure index of 30%, however in sequential doses, of 60
      mg/kg during 3 days or 30 mg/kg, 6 days, cure percentage is elevated to 95%,
      evaluated by oogram. The evaluation of the treatment by quantitative or
      qualitative examination methods does not show the same sensibility. The
      percentage of cure according to feces examination, the quantitative of Kato-Katz
      or the qualitative (sedimentation), showed indexes from 90 to 100%, for either
      one of the drugs, even in single dose, which evidences the difference of
      methodology of therapeutic evaluation. Tolerance to both medicaments is from good
      to regular, with collateral effects in 30 to 40% of the patients.

PMID- 1343922
TI  - [Sclerotherapy of esophageal varices in schistosomiasis patients].
AB  - To assess the therapeutic possibilities of injection sclerosis in schistosomotic
      portal hypertension, a 5-year prospective study was conducted in northeast
      Brazil, where this parasitosis is endemic. Fifty patients undergoing endoscopy
      for upper gastrointestinal hemorrhage from rupture of esophageal varices from
      July through December 1981 were chosen for the study. The 32 consenting patients
      were submitted to injection sclerotherapy paravariceally, using ethanolamine
      oleate; the 18 refusing to participate were assigned to the control group. The
      incidence of rebleeding was 28.1% in the former and 44.5% in the latter, a
      difference which was not statistically significant (Fisher's test, p = 0.375).
      Mortality from rupture of esophageal varices was 3.1% in the sclerotherapy group
      and 27.7% in the control group, a statistically significant difference (Fischer's
      test, p = 0.017). Since sclerotherapy markedly improved the long-term survival
      rate of the patients, this procedure is advocated for the treatment of esophageal
      varices in cases of portal hypertension due to schistosomiasis.

PMID- 1343923
TI  - [Critical evaluation of schistosomiasis portal hypertension surgery].
AB  - There are over 100,000 patients affected by schistosomotic portal hypertension,
      that may suffer rupture of the esophageal varices. Besides the portal
      hypertension, local factors must be emphasized as responsible for the three
      distal centimeters of the esophagus, called "zona vulneravel" (vulnerable zone).
      The better liver functional reserve of these schistosomotic patients as compared
      to the cirrhotic, present two favorable conditions: (1) better possibility of
      conservative treatment during acute hemorrhage; (2) elective surgical treatment
      may be undergo without a mandatory step of large portal decompression. The Author
      only indicate surgical treatment in patients with hemorrhage antecedent and his
      preference consist in splenectomy plus obliterative suture of the varices at the
      "vulnerable zone" and when possible, ligature of left gastric vein also; 358
      patients were undergone surgery with operative mortality 3.07%; 347 were followed
      during 1 to 25 years; late mortality 8.38%; recurrence hemorrhage 11.58%; none
      porto-systemic encephalopathy was observed.

PMID- 1343924
TI  - Influence of the host related factors in the development of the hepatosplenic
      form of schistosomiasis mansoni.
AB  - The frequency of hepatosplenomegaly in endemic areas is not proportional to the
      fecal ova count. This may be explained by epidemiological genetic. The occurrence
      of two or more cases of schistosomal hepatosplenomegaly in nuclear family is much
      higher than expected. The concentration is higher among siblings than it is among
      mothers and children of father and children. It is not significant between father
      and mother. If the mother, instead of the father, has hepatosplenic
      schistosomiasis the relative risk for the child to acquire hepatosplenomegaly is
      at least five times (the maternal affect). The inbreeding is higher in the
      hepatosplenic than in the hepato-intestinal patients. In some areas in Brazil the
      hepatosplenic form of the schistosomiasis mansoni occurs with much higher
      frequency in whites than in blacks. After treatment, reversion of hepatosplenic
      schistosomiasis occurs more frequently in non-whites. It seems that the
      resistance of blacks to the hepatosplenic form of schistosomiasis may be related
      to the glyoxalase system, perhaps associated to another genetic marker. The
      hepatosplenic schistosomiasis is less frequent in longilineal individuals. In
      some areas the hepatosplenic form of schistosomiasis is more frequent in A blood
      group of ABO system. The family heredograms do not suggest a single mendelian
      inheritance, but probably a multifactorial and possibly polygenic one.

PMID- 1343925
TI  - Harmonization of research and control in schistosomiasis.
AB  - I have been employed by several different organizations during over 30 years
      working on schistosomiasis, the majority spent in endemic areas of the Caribbean,
      South America, Africa and the Western Pacific. Much of the work is best
      classified as applied research but sometimes it strayed to the extremes of either
      public health control programmes or pure research. Over this period, there have
      been several significant research developments that have altered our whole
      approach to control. Ideally, research and control should complement each other
      but, in reality, they sometimes have conflicting objectives. Public health
      workers understandably wish to provide immediate, short-term protection to the
      communities in their care, but research workers may, within ethical limits,
      reasonably want to observe untreated communities for extended periods in order to
      understand the underlying processes of transmission, disease pathogenesis and
      immunity to help develop more effective control measures. An example of this
      situation has occurred recently in Senegal where water development projects seem
      to have favoured the introduction and spread of Schistosoma mansoni in the
      Senegal River Basin. I have been asked to be the scientific consultant to the
      newly formed ESPOIR programme, linking European research organizations and the
      Senegal Ministry of Health, to reconcile the conflicting aims of public health
      workers, wishing to use whatever funds can be obtained for an immediate
      chemotherapy to try to eliminate the focus, at present confined to the vicinity
      of a relatively small, commercially run sugar irrigation scheme; and research
      workers who see a rare chance to study the development of immune mechanisms in a
      adults in a community not previously exposed to the infection.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1343926
TI  - Parasite enzymes as a tool to investigate immune responses.
AB  - Previous evidences reported by us and by other authors revealed the presence of
      IgG in sera of Schistosoma mansoni-infected patients to immunodominant antigens
      which are enzymes. Besides their immunological interest as possible inductors of
      protection, several of these enzyme antigens might be also interesting markers of
      infection in antibody-detecting immunocapture assays which use the intrinsic
      catalytic property of these antigens. It was thus thought important to define
      some enzymatic and immunological characteristics of these molecules to better
      exploit their use as antigens. Four different enzymes from adult worms were
      partially characterized in their biochemical properties and susceptibility to
      react with antibodies of infected patients, namely alkaline phosphatase (AKP,
      Mg2+, pH 9.5), type I phosphodiesterase (PDE, pH 9.5), cysteine proteinase (CP,
      dithiothreitol, pH 5.5) and N-acetyl-beta-D-glucosaminidase (NAG, pH 5.5). The
      AKP and PDE are distinct tegumental membrane-bound enzymes whereas CP and NAG are
      soluble acid enzymes. Antibodies in infected human sera differed in their
      capacity to react with and to inhibit these enzyme antigens. Possibly, the
      specificity of the antibodies related to the extent of homology between the
      parasite and the host enzyme might be in part responsible for the above
      differences. The results are also discussed in view of the possible functional
      importance of these enzymes.

PMID- 1343927
TI  - Protein-DNA associations in a gender-specific gene of Schistosoma mansoni:
      characterization by UV cross-linking, DNase I footprinting and band shift assays.
AB  - Protein extracts obtained from male and female schistosomes were incubated with a
      gender-specific gene, F-10, transcribed only in adult females and encoding a
      major egg-shell protein. The protein/DNA interaction was measured using the band
      shift, DNase-I-footprinting and UV cross-linking techniques. The results showed a
      clear band shift when a 302 bp restriction fragment containing the 3' end of the
      gene was incubated with either female or male proteins. This fragment also
      contained a putative steroid hormone regulatory element (HRE). In contrast, only
      the male proteins produced a shift with the 495 bp fragment corresponding to the
      middle region of the gene. DNase I footprinting showed that proteins from males
      and females interacted with the F-10 gene by binding to multiple adjacent sites
      along the DNA, thus generating relatively long protected fragments of
      approximately 100 bp. This result suggested that the adjacent binding of several
      moles of protein occurred at the 5' end of the gene. UV cross-linking between
      schistosome proteins and a 21 bp synthetic oligonucleotide containing the F-10
      HRE, evidenced proteins having MWS of 30, 45 and 65 kDa. These proteins are
      presumably involved in the regulation of transcription of the F-10 gene.

PMID- 1343928
TI  - The p53 gene expression and its developmental regulation in schistosomes.
AB  - We have studied the gene expression, especially of the oncoproteins, and its
      regulation in schistosomes. Schistosomes have a complex life cycle with a defined
      dimorphic lifestyle. The parasite are so far unique in biology in expressing
      oncogene products in their adult stage. In order to characterize the expression
      and developmental regulation, a lambda gt 11 cDNA library and lambda EMBL4
      genomic DNA library of each growth stage of Schistosoma mansoni and S. japonicum
      was constructed, and was screened with various monoclonal antibodies against
      oncogene products. One positive plaque reacted to anti-p53 antibody (Ab-2,
      Oncogene Science, Inc.) was further analyzed. This fusion protein was about 120
      KDa in molecular weights, and expressed as 1.4 Kb RNA in the adult stage. P53
      gene is well-known as the negative regulator of the cell cycle, and the mutations
      in the gene are turning out to be the most common genetic alterations in human
      cancers. The comparison of the gene structure among species and stages were being
      conducted. Chromosome structures, C-band formation, and the results of in situ
      hybridization using the phage probe would be discussed.

PMID- 1343929
TI  - The role of egg antigens, cytokines in granuloma formation in murine
      schistosomiasis mansoni.
AB  - The induction of granuloma formation by soluble egg antigens (SEA) of Schistosoma
      mansoni is accompanied by T cell-mediated lymphokine production that regulates
      the intensity of the response. In the present study we have examined the ability
      of SDS-PAGE fractionated SEA proteins to elicit granulomas and lymphokine
      production in infected and egg-immunized mice. At the acute stage of infection
      SEA fractions (< 21, 25-30, 32-38, 60-66, 70-90, 93-125, and > 200 kD) that
      elicited pulmonary granulomas also elicited IL-2, IL-4 lymphokine production. At
      the chronic stage a diminished number of fractions (60-66, 70-90, 93-125, and >
      200 kD) were able to elicit granulomas with an overall decrease in IL-2, IL-4
      production. Granulomas were elicited by larval-egg crossreactive and egg-specific
      fractions at both the acute and chronic stage of the infection. Examination of
      lymphokine production from egg-immunized mice demonstrated that as early as 4
      days IL-2 was produced by spleen cells stimulated with < 21, 32-38, 40-46, 93
      125, and > 200 kD fractions. By 16 days, IL-2 production was evoked by 8 of 9
      fractions. IL-4 production at 4 days in response to all fractions was minimal
      while at 16 days IL-4 was elicited with the < 21, 25-30, 50-56, 93-125, and > 200
      kD fractions. The present study reveals differences in the range of SEA fractions
      able to elicit granulomas and IL-2, IL-4 production between acute and chronic
      stages of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343930
TI  - The role of cytokines in the pathogenesis of hepatic granulomatous disease in
      Schistosoma mansoni infected mice.
AB  - Cytokines are important in the cell-mediated response to Schistosoma mansoni
      eggs. We have found that Th2 cytokine responses (e.g. IL-4 and IL-5) are
      augmented after egg laying begins while Th1 responses (IL-2 and IFN-gamma) are
      down regulated in S. mansoni infected mice. Treatment of mice with anti-IL-5
      monoclonal antibodies (Mab) suppressed the eosinophil response almost completely
      but did not affect granuloma size and slightly increased hepatic fibrosis. Anti
      IL-4 treatment abolished IgE responses in infected mice and decreased hepatic
      fibrosis slightly. Anti-IFN-gamma treatment had no effect on hepatic pathology.
      Anti-IL-2 treatment decreased granuloma size significantly and decreased hepatic
      fibrosis markedly. Anti-IL-2 treatment dramatically decreased IL-5 secretion by
      splenic cells in vitro and decreased peripheral blood and tissue eosinophilia. In
      contrast IL-4 secretion was unaffected and serum IgE was normal or increased. IL
      2 and IFN-gamma secretion by splenic cells of treated mice were slightly but not
      significantly increased suggesting that anti-IL-2 treatment is affecting Th2
      rather than Th1 responses.

PMID- 1343931
TI  - The susceptibility of adult schistosomes to immune attrition.
AB  - Mouse infection models are described that demonstrate reduction of egg production
      in Schistosoma haematobium infections and both worm loss and reduced fecundity in
      S. bovis infections. Neither phenomenon could be shown in S. mansoni infected
      mice. The immunological basis for these anti-adult responses was inferred by
      comparison with infections in T-cell deprived mice and by serum transfer of the
      ability to reduce a S. bovis worm burden into immunocompromised hosts.
      Vaccination with irradiation attenuated parasites was also shown to have
      consequences for the adults of a challenge infection of S. haematobium and S.
      bovis specifically. Prior vaccination resulted in an abrogation of the anti
      fecundity and adult worm elimination that occurred in non-vaccinated similarly
      infected mice. These models are being used to define the targets and mechanisms
      involved in anti-adult attrition. A serological assay, quantitation of a
      circulating antigen (CAA) has been assessed for its ability to measure worm
      burdens of different species of schistosome in mice. This assay will be used to
      question whether anti-adult immunity contributes to the pattern of infection with
      S. mansoni and S. haematobium in man.

PMID- 1343932
TI  - Recent advances in immunity to human schistosomiasis.
AB  - For many years the epidemiological significance of immunity in human
      schistosomiasis has been the subject of inconclusive debate. Recently, the
      results of studies from Brazil and Kenya, on Schistosoma mansoni and from
      Zimbabwe and The Gambia on S. haematobium have confirmed the importance of
      protective immunity. In communities in endemic areas the development of immunity
      to infection only occurs after many years of exposure. In part this is due to the
      slow development of antibodies which are protective but also to the earlier
      development of antibody isotypes which lack protective capacity and which are
      capable of interfering with the functioning of protective antibodies. Protective
      antibodies appear to be of the IgE class but some IgG subclasses may also be
      important. Initially, blocking antibodies were thought to be predominantly IgM
      and IgG2 but IgG4 also seems to possess blocking activity. The early production
      of blocking antibodies and late production of protective antibodies may be
      indicative of cytokine induced immunoglobulin class switching caused by the
      sequential involvement of different lymphokines.

PMID- 1343934
TI  - The mouse ligated intestinal loop assay for the studies on enteroinvasive
      Escherichia coli.
AB  - Enteroinvasive Escherichia coli exhibited a positive reaction in the mouse
      intestinal loop assay except for noninvasive mutant strains. These mean values of
      fluid weight per gut length of mouse loops inoculated with enteroinvasive E. coli
      were significantly higher than that given by brain heart infusion broth. Oedema
      and swelling in all positive loops, increased bacterial cell numbers within
      intestinal loops were observed.

PMID- 1343933
TI  - Human IgE responses to Schistosoma mansoni and resistance to reinfection.
AB  - Schistosoma mansoni infected Kenyan patients were treated and the intensities of
      their reinfections were followed over the next two years. In addition, their pre-
      and six month post-treatment serum levels of IgG1-4, IgM, and IgE, specific for
      schistosomula, egg and adult worm, were measured in ELISA. No reinfection took
      place before six months post-treatment. Reinfection intensities varied with age;
      the younger children becoming reinfected at significantly higher intensities than
      older individuals. When antibody and reinfection levels were compared, only the
      six month post-treatment IgE response against adult worm correlated negatively
      with intensities of reinfection and, therefore, was predictive of resistance or
      immunity to reinfection. IgE and IgG specific Western Blots were carried out. The
      adult worm antigens recognized by IgE were restricted compared with the IgG
      responses of the same patients, although no individual antigen was uniquely
      recognized by the IgE isotype. A dominant 22 kDa antigen was recognized by most
      but not all high IgE responders. Patients with IgE responses against this antigen
      suffered significantly lower subsequent levels of reinfection, compared with non
      responders. A monospecific rabbit antiserum against the 22 kDa adult worm antigen
      showed that this antigen is specifically located in the tegument of the adult
      worm and of 'lung' and 'liver' stage schistosomula, but is absent from the early
      'skin' schistosomula. It is possible that this antigen is a target for human IgE
      mediated immune effector mechanisms active against the post skin stage
      schistosomula and that this is boosted by the death of adult worms.

PMID- 1343935
TI  - Phospholipid content of untreated and insulin treated cells of Neurospora crassa
      (wall-less strain).
AB  - Phosphatidylcholine (51.2%) and phosphatidyl-ethanolamine (38.3%) are the most
      abundant phospholipids in the wall-less strain of Neurospora crassa. Insulin
      treatment exerted no change on the amount of phosphoinositides, although some
      previous results proved the existence of specific insulin receptors and specific
      effect of insulin on glucose metabolism in these cells. Long (20 h) treatment
      with insulin also failed to cause biologically significant changes.

PMID- 1343937
TI  - Anthraquinone pigments production by brown mutant Trichoderma viride M-108 under
      various nutrition conditions.
AB  - In this work the influence of 12 carbon and 9 nitrogen sources on pigment
      production of brown mutant Trichoderma viride M-108 was tested. There were two
      concentrations of nutrient sources used and the tests were carried out in three
      light regimes. The pigmentation was good only on media containing sodium nitrate,
      sodium nitrite, sucrose, starch and glycerol and there was no pigment production
      on media with adenine, ammonium chloride and ammonium sulphate. In mixtures of
      pigments, individual compounds were determined by using thin-layer chromatography
      and UV spectra of colour fractions.

PMID- 1343936
TI  - The course of LCMV infection in euthymic and athymic mice pretreated with
      immunomodulatory agents.
AB  - Balb/c (euthymic) and nu/nu (athymic) mice were treated intraperitoneally with TP
      4 (a synthetic tetrapeptide, thymopoietin sequence analog) or with Mannozym (1%
      zymosan suspension), and were infected intracerebrally with LCM virus. Both of
      the agents contributed to the development of fatal choriomeningitis, consequently
      stimulated the cellular immune response in euthymic mice, but the athymic mice
      either treated or not, survived the infection, consequently the agents had no
      effect on the course of LCM virus infection. Both agents exerted a thymus
      dependent cellular immune response stimulating effect. That is, an
      immunostimulatory effect can be realized only in the presence of the thymus or
      the T-dependent lymphoid system.

PMID- 1343938
TI  - Reversion of UV light morphological and colour mutants of Trichoderma viride.
AB  - By using UV light 13 years ago from Trichoderma viride 8-7 Pers. ex S. F. Gray 82
      colour and morphological mutants were prepared. The reversion of these mutants
      was high and in 1985 only 26 stable mutants (i.e. 32%) could be used for genetic
      studies. In 1991, from these 26 mutants we had only 6 stable types (i.e. 7.3%
      from the original state). These mutants were permanently transferred on fresh
      CzDA medium every 3-4 months and checked for morphology, growth, conidiation,
      heterokaryons and diploids production. The group of mentioned mutants was
      enlarged with mutants which were after 3-4 transfers on fresh medium, preserved
      dried to the present time. The largest differences were observed in microscopic
      appearance of colonies. Differences between growth rates, intensity of
      conidiation were comparable with those made 13 years ago.

PMID- 1343939
TI  - Ochratoxigenicity of Aspergillus ochraceus group and Penicillium verrucosum var.
      cyclopium strains on various media.
AB  - Production of ochratoxin A (OA) by strains of Aspergillus ochraceus group (A.
      ochraceus--21, A. sclerotiorum--1, A. sulphureus--1) and Penicillium verrucosum
      var. cyclopium strains--11, on various media was investigated. Thirteen percent
      of A. ochraceus strains and 18% of P. verrucosum var. cyclopium formed OA growing
      on sterile crushed wheat for 14 days at 25 to 27 degrees C (preliminary
      experiments). Toxin concentrations were 5.0 to 7.0 micrograms/kg. Five strains OA
      positive on crushed wheat and four OA-negative strains were cultivated on various
      liquid nutritional media (YES, RM, OAT, CG and AFP). All the strains tested,
      including OA-negative ones, produced OA on certain liquid media. Concentrations
      of OA were low again (trace to 16.0 micrograms/l). The largest number of mould
      strains examined produced OA on YES (55.5%) and RM media (44.0%), but the highest
      concentration (16.0 micrograms/l) was formed on YES and CG media.

PMID- 1343940
TI  - Antibodies against invasion plasmid coded antigens of shigellae in human
      colostrum and milk.
AB  - Colostral and milk samples of Swedish, Vietnamese and Costa Rican mothers living
      under various socioeconomic conditions were tested for the presence of shigella
      invasion plasmid coded antigen (Ipa) specific antibodies. IgA antibodies of this
      specificity were found in significantly higher titres in samples of Vietnamese
      (600 +/- 338) than in samples of Swedish or high income Costa Rican mothers (190
      +/- 224 and 290 +/- 241, respectively; p < 0.05). Specific IgA titres in the low
      income group of Costa Rican mothers (470 +/- 338) did not differ significantly
      from the values obtained in Vietnam. While no Ipa specific IgM could be detected
      in any of the samples tested, specific IgG was found in 90% of the Vietnamese
      colostrum. These data indicate that antibodies which could be responsible for the
      dysentery-preventing effect of breast feeding are indeed present in human
      colostrum and milk in areas where shigellosis occurs with relatively high
      incidence.

PMID- 1343942
TI  - Chloroquine inhibits the insulin binding and the imprinting of nuclear envelope
      in Tetrahymena.
AB  - Chloroquine possessing lysosomotrop effects inhibits the development of insulin
      imprinting both on the plasma membrane and the nuclear envelope. Simultaneously
      chloroquine can inhibit the insulin binding in the nucleus itself but not in the
      plasma membrane. There is a dose dependent increase of binding of labelled
      insulin to the nuclear envelope. The control related binding of nuclei pretreated
      with insulin or chloroquine is similar and have a direct ratio, independently of
      the applied concentrations.

PMID- 1343941
TI  - Effect of inhibitors of HeLa cell structures and functions on Escherichia coli
      HB101 (PRI203) entry process.
AB  - We investigated the effect of some eucaryotic cytoplasmic structure and function
      inhibitors on the entry into HeLa cells of the Escherichia coli HB101 K12 strain,
      harbouring the recombinant plasmid pRI203, in which is cloned a 3.2 Kb
      chromosomal fragment of Yersinia pseudotuberculosis. Substances impairing
      microfilament structures and functions (cytochalasin B and trifluoroperazine)
      significantly reduced invasion ability whereas microtubule organization
      inhibitors (colchicine and vinblastine) were ineffective. Data obtained with a
      lipophilic weak base (methylamine), which raises the pH of intracellular
      vesicles, demonstrated that, in entry pathway of E. coli HB101 (pRI203), endosome
      acidification is not required. Host cell energy has been shown to contribute to
      bacterial internalization since the presence of oxidative phosphorylation and
      glycolysis inhibitors (sodium azide, 2-dinitrophenol and 2-deoxy-D-glucose)
      during the invasion process, affected bacterial entry.

PMID- 1343943
TI  - Evaluation of indirect enzyme linked immunosorbent assay for the detection of
      coxsackieviruses in clinical samples and its comparison with dot-immunobinding
      assay.
AB  - Indirect enzyme linked immunosorbent assay (ELISA) was applied for the direct
      detection of coxsackieviruses in clinical samples viz. rectal swabs (RS) and
      throat swabs (TS) collected from patients admitted to various nursing homes and
      local hospitals. Results indicate the presence of different CVA types in 65
      (62.5%) out of 104 RS, and 18 (52.9%) out of 34 TS samples. Dot-immunobinding
      assay was also standardized for the identification of CVA types employing 52 RS
      samples and the results compared with indirect ELISA. Dot-immunobinding detected
      more CVA types in a relatively larger number of specimens than indirect ELISA.

PMID- 1343944
TI  - Latex agglutination and adenoviruses. I. Detection of polyclonal antibodies by
      latex agglutination test.
AB  - A latex agglutination (LA) test was developed for the detection and measurement
      of polyclonal anti-adenovirus antibodies. Latex particles, coated with purified
      hexon, penton or fibre antigens displayed specific agglutination with 21 rabbit
      immune sera directed against the different antigens and the complete virus of 10
      human and 2 animal adenovirus types. The sensitivity of LA was compared to that
      of passive haemagglutination, complement fixation (CF) and immunodiffusion
      reactions. In experiments with immune sera as well as with human serum samples
      the sensitivity of LA test proved to be in the same range as that of CF test.
      Because of its easy and rapid performance (slide agglutination within 4 min) LA
      method may substitute for CF reaction in serological adenovirus diagnosis.

PMID- 1343945
TI  - Diazald, a newly recognized antimicrobial agent and its spectrophotometric
      determination.
AB  - Diazald, a chemical intermediate for the synthesis of biologically active
      compounds, was found to be a potent in vitro antimicrobial agent against yeasts,
      yeast-like and filamentous fungi as well as Gram-positive and Gram-negative
      bacterial strains. Its activity is not inhibited by either para-aminobenzoic acid
      (PABA) or the nitroso group-specific 2-aminothiazole-methoxyimino acetic acid
      (ATMAA). This suggests that the molecule as such is responsible for the
      antimicrobial activity. For its quick measurement a sensitive spectrophotometric
      method has been developed.

PMID- 1343946
TI  - Adherence of ruminal Streptococcus bovis and Lactobacillus strains to primary and
      secondary cultures of rumen epithelium.
AB  - Six strains of rumen Lactobacillus and four Streptococcus bovis strains isolated
      from rumen wall and fluid samples were examined for the adherence to cells of
      primary and secondary cultures of ruminal epithelium (REC) prepared from sheep
      and calf. S. bovis adhered to the keratinized REC. Ruminal lactobacilli did not
      adhere. The presence of rumen lactobacilli in mixture had no influence on the
      adherence of S. bovis strains. No difference was observed in the adherence of
      tested bacteria to epithelial cells of primary or secondary cultures, but
      adhesion was only detected on keratinized cells.

PMID- 1343947
TI  - Blood pressure measurements and intravenous infusions.

PMID- 1343948
TI  - Strategies for implementation and quality assurance for mammographic screening.
AB  - Compliance with screening mammography guidelines is affected by complex factors,
      including cost, accessibility, education, and attitudes of referring physicians.
      High-volume mammography facilities have lower fees and higher quality. Quality
      assurance is the focus of the voluntary American College of Radiology Mammography
      Accreditation Program, and over half of all mammography units are accredited.
      Nonetheless, pressure for mandatory quality standards is increasing. Mobile
      mammography reduces costs and increases access, but it presents challenges in
      financing and quality assurance. These screening issues, especially quality
      assurance, are not taught adequately in radiology residency training programs.
      Yet public awareness of the benefits of early detection has resulted in more
      lawsuits for failure to diagnose and delay in diagnosis. Preventive measures
      reduce medicolegal risks. On a personal level, the psychologic trauma of
      screening mammography is greater than was previously suspected. However,
      associated anxiety and stress do not seem to affect compliance with screening
      guidelines adversely.

PMID- 1343950
TI  - Branemark Cera One single tooth abutment.

PMID- 1343949
TI  - Thoracic intervention.
AB  - The literature of the past year regarding interventional procedures in the thorax
      covers aspects of transthoracic needle biopsy, drainage of pleural fluid
      collections, percutaneous management of lung abscess, and thoracic vascular
      interventions. Topics in transthoracic needle biopsy include a large
      retrospective series on fluoroscopically guided biopsy of thoracic masses;
      several reports reviewing experience with diagnosis of anterior mediastinal
      masses, including four studies describing the use of real-time ultrasound
      guidance for this procedure; the description of a new automated cutting needle
      for consistent tissue sampling; and two studies addressing factors affecting
      pneumothorax and chest tube insertion rates following transthoracic needle
      biopsy. Reports on percutaneous management of pleural fluid collections are
      highlighted by a paper reporting the results of ultrasound-guided drainage and
      sclerosis of malignant pleural effusions. Ultrasound-guided percutaneous
      aspiration of lung abscess for isolation of causative bacteria is the basis of
      two recent papers, and successful CT-guided drainage of lung abscesses is
      described by a group of researchers that has written extensively on a variety of
      the interventional thoracic procedures that are currently performed. Finally, the
      failures and complications associated with bronchial and pulmonary arterial
      embolization procedures have been reviewed.

PMID- 1343951
TI  - Professional negligence.

PMID- 1343952
TI  - The single tooth implant: tissue response, oral hygiene and clinical
      instrumentation.

PMID- 1343953
TI  - An implant restoration as the primary treatment alternative replacing a maxillary
      first bicuspid tooth.

PMID- 1343954
TI  - Electric discharge machining in implant prosthodontics.

PMID- 1343955
TI  - Kilovoltage peak and half value layer relationships of a dental X-ray machine.
AB  - This study compares the recorded kilovoltage peak (kVp) on the control panel
      versus actual kVp measured by the Photon Physics instrument and Non-invasive
      Evaluator of Radiation Output (NERO) System. The study also measures the effects
      of kVp and milliampere (mA) on Half Value Layer (HVL). Kilovoltage peak was
      measured using a photon physics instrument and the NERO system. Half value layer
      was measured using aluminum as the absorber. The kVp and HVL were measured from
      50 to 100 kVp at 5 kVp intervals using both 10 mA and 15 mA. Results show a 2 to
      6 kVp difference between recorded kVp on the control panel of the dental x-ray
      machine and measured kVp using the photon physics instrument. There was 10-15 kVp
      difference between the recorded kVp on the control panel and kVp measured with
      the NERO Quality Assurance System. The measured kVp on photon physics or NERO
      system was always greater than the recorded kVp on the control panel. The HVL
      increased as the kVp increased for both 10 mA and 15 mA settings. However, above
      80 kVp, the HVL increase was not significant.

PMID- 1343956
TI  - Cementum and bone: a histomorphometric study.
AB  - In the present study, a series of cementum and bone specimens were examined both
      qualitatively and quantitatively with a view to establishing histological
      criteria which may help in differentiating cementum from bone. This is for the
      first time that differences in cellularity and width of fibre bundles between the
      lamellar bone and the cementum has been reported.

PMID- 1343957
TI  - Evaluation of decalcified allogenic bone matrix grafts in and around root apices.
      A histological study.
AB  - Decalcified Allogenic Bone grafts were implanted in and around eighteen root
      apices after apicoectomy. The procedure was carried out on eighteen rabbits,
      dividing them into three groups of six rabbits each. The animals were sacrificed
      after 48-72 hours, 8-10 days & 8-10 weeks period of interval. Result of the
      present investigation reveal that DABM grafts stimulate osteogenesis and
      cementogenesis after the initial phase of inflammation. Tissues simulating bone
      and cementum appear at the apical end, speculating that the grafts would
      certainly result in physiological sealing of root apices. The possibility of
      saving the life of non vital teeth with or without wide apical foramen will
      enhance in future.

PMID- 1343959
TI  - Ethics in science: the publication process.

PMID- 1343958
TI  - Osteoradionecrosis of mandible in patients treated with definitive radiotherapy
      for carcinomas of oral cavity and oropharynx. A retrospective study.
AB  - A retrospective analysis of 1140 cases of cancer of oral cavity and oropharynx
      treated with definitive radiotherapy was carried out with regard to the incidence
      and precipitating factors of mandibular osteoradionecrosis. 14 cases developed
      osteoradionecrosis out of which 10 had spontaneous mandibular necrosis and 4 had
      dental extractions in the area where osteoradionecrosis developed. Amongst the 10
      cases of spontaneous osteoradionecrosis, 8 patients received doses of 6500 cGy in
      6 1/2 weeks or 7000 cGy in 7 weeks by megavoltage cobalt 60 teletherapy and the
      remaining two patients received the doses of 6000 cGy in 6 weeks. The aforesaid 4
      patients of osteoradionecrosis in the area of dental extractions had received
      doses of only 6000 cGy in 6 weeks.

PMID- 1343961
TI  - Arterial blood pressure and blood glucose levels in oral lichen planus patients
      in Calcutta (India).
AB  - The Arterial Blood pressure and Blood Glucose levels of 192 patients with Oral
      Lichen Planus was determined. A control sample of 5000 healthy individuals was
      also studied for comparison with the oral Lichen Planus cases. No significant
      difference was found between oral Lichen Planus patients and the general
      population with respect to Blood pressure and Blood Glucose values.

PMID- 1343960
TI  - Caridex: dentin topography and bond strength evaluation.
AB  - CARIDEX, is a new approach to pediatric operative dentistry. An in vitro study
      with the aim of comparing the efficacy of the CRS system against the conventional
      caries removal system was carried out by studying the dentin topography following
      caries removal by the two systems restorative materials--Silver amalgam,
      Composite resin, Glass Ionomer, IRM nad Poly--F to the CARIDEX treated dentin
      using the Housfield Tensometer. The results were evaluated statistically and
      significant results were observed.

PMID- 1343962
TI  - Electrogustometry in oral submucous fibrosis. A study in 50 cases.
AB  - Taste sensation were evaluated in 50 cases of Oral Submucous Fibrosis.
      Ankyloglossia was present in 28% and ulceration of tongue in 6% of cases. None of
      the cases had subjective impairment of taste sensation. Electrogustometry
      revealed impairment of taste in 46% of cases. Ankyloglossia was found to be
      related with the severity of Oral Submucous Fibrosis but impairment of taste was
      not related with the severity of the disease. The possible mechanism of the
      impairment of taste is discussed in brief.

PMID- 1343963
TI  - Influence of opioids on LH secretion in gilts during the estrous cycle.
AB  - The effect of endogenous opioid peptides (EOP) on LH secretion is variable during
      different physiological states. A series of experiments concerning the role of
      EOP on LH secretion in cyclic gilts was performed. They were comprised of (1) an
      administration of an opioid antagonist or agonist in gilts during the estrous
      cycle and in ovariectomized (OVX) gilts in which the LH surge was induced with
      estradiol benzoate (EB) and (2) in vitro studies on GnRH release from the stalk
      median eminence (SME) of cyclic gilts and OVX estrogen and progesterone primed
      gilts in response to naloxone (NAL). Naloxone and met-enkephalin analogue (FK 33
      824) administration as a single independent injections did not affect LH
      secretion during the early (Day 16) or late (Day 19 or 20) follicular phase.
      However, continuous infusion of FK 33-824 for 4 h decreased LH secretion during
      the infusion period on Day 19 of the estrous cycle. Morphine also exerts an
      inhibitory effect on the EB-induced LH surge during the positive feedback phase
      (60-64 h after EB administration) in OVX gilts. On the contrary, NAL infusion in
      OVX gilts during the negative feedback phase (30-34 h after EB administration)
      did not alter LH secretion. A single injection of FK 33-824 in luteal phase gilts
      decreased the number of LH pulses for a 3 h period. This allows to hypothesize
      that EOP participates in the regulation of pulsatile LH secretion in pigs during
      the luteal phase. In vitro studies indicate that influence of EOP on LH secretion
      also takes place at the SME level. GnRH efflux from the SME of gilts during the
      luteal and late follicular phases was augmented in the presence of NAL.
      Unexpectedly, the priming of OVX gilts with estrogens caused the highest increase
      in GnRH release from the SME in vitro in response to NAL. These results confirm
      the variety of functional links between the opioid system and LH secretion in
      gilts during different stages of the estrous cycle.

PMID- 1343964
TI  - Regulation of bovine intra-luteal function by peptide hormones.
AB  - There is increasing evidence for the existence of substances in ovarian tissues
      and fluids which are able to act locally, either alone or by modulating the
      actions of the gonadotropins, thus modifying the functions of ovarian cells.
      There are now clear data for oxytocin (OT), insulin-like growth factor-1 (IGF-1)
      and basic fibroblast growth factor (bFGF) in luteal tissue, with regard to
      specific expression of mRNA, secretion of peptid and receptors. Biological
      effects of these growth factors and others on luteal tissue were determined
      during the estrous cycle using two different in vitro systems; a novel
      microdialysis system (MDS) of intact luteal tissue and culture of luteal cells.
      The concentrations of secreted progesterone and OT were used as parameters. MDS;
      OT was most stimulative during the early luteal phase (days 5-7) and decreased
      continuously from days 8-12 to days 15-18. During early and mid stages bFGF was
      the most potent stimulator and at the late stage IGF-1 and IGF-2 were most
      stimulatory. Transforming growth factor beta (TGF-beta) stimulated the release of
      OT most effective at the early luteal stage. Results from the cell culture system
      (where no cell to cell contact exists) showed a different pattern. IGF-1 and IGF
      2 had a stimulatory effect during long and short term stimulation, bFGF only
      during short term and OT showed no effect. Receptors were found for all peptides
      examined of luteal cells. A model of an intraovarian cascade-like system for the
      amplification of luteal function is presented.

PMID- 1343965
TI  - Role of the noradrenergic system in the secretory function of the corpus luteum.
AB  - The importance of sympathetic innervation changed significantly during sexual
      maturation and in the course of the oestrous cycle in females. Basal secretion of
      progesterone is partly dependent on constant beta-adrenergic stimulation since
      local infusion of propranolol (beta-blocker) into the ovary decreased
      progesterone secretion by 20-30% of pre-treatment value. Noradrenaline given into
      the abdominal aorta in the moderate doses affected very quickly and dramatically
      the secretory function of the corpus luteum during the luteal phase in cattle and
      also in other species. Thus short-lasting mobilization stress protects and even
      supports corpus luteum function. This effect is exerted through the stimulation
      of beta-adrenoceptors which then activates specific intracellular enzymes.
      Additionally noradrenaline acts upon vascular alpha-receptors and increase
      ovarian blood flow allowing utilization of serum-derived lipoprotein as a source
      of cholesterol for steroidogenesis. The highest amount of specific beta-receptors
      in luteal membranes was found in the newly-formed corpus luteum which does appear
      to require noradrenergic support especially at that stage of its development. The
      mechanism of noradrenaline influence upon luteal cells resulting concomitant
      progesterone and ovarian oxytocin secretion is, however, obscure. It is suggested
      that intracellular second messengers (cAMP, Ca2+) involved in noradrenaline
      action can simultaneously affect the secretion of both these hormones and this
      indicates some functional relationship between them. The presented results are
      focused mainly upon cattle due to the importance of this species among other
      domestic animals. Nevertheless for comparison data from other species are also
      quoted.

PMID- 1343966
TI  - Experimental and practical approaches to the establishment and maintenance of
      pregnancy.
AB  - A series of three large field trials was carried out to assess the effect of
      buserelin on fertility in dairy cows. In the first, 10 micrograms buserelin was
      injected on the day of insemination. There were no significant effects on
      fertility parameters compared to untreated controls. In the second trial cows
      were injected on day 12 after insemination. Mean pregnancy rates to first
      insemination were 53.4 and 65.4% for control and treated cows respectively (P <
      0.01). Mean pregnancy rates to repeat inseminations were 52.9 and 59.4% for
      control and treated cows (NS). Mean calving to conception intervals were 91.4 and
      85.3 days (P < 0.01) and the incidence of barren cows was 10.2 and 5.3% (NS).
      Overall the economic benefit of buserelin injection on day 12 was calculated to
      be 27.43 pounds per cow treated excluding the cost of the treatment. In trial 3
      cows were injected with buserelin either on day 8 or 10 after insemination. There
      were no significant effects on fertility parameters compared to untreated control
      cows. In a fourth trial ewes were injected with 4 micrograms buserelin on day 12
      after service. There were indications that both pregnancy rate and lambing
      percentage could be increased by buserelin treatment. Daily blood samples were
      collected from 5 dairy cows during a control cycle and a cycle in which 10
      microgram buserelin was injected on days 11 and 13. Cycle length was unaffected
      by treatment and the concentration and pattern of progesterone secretion did not
      differ between control and treated cycles. Plasma oestradiol concentrations were
      similar in the control and treated cycles before day 11. However from day 12 to
      16, equivalent to the time of maternal recognition of pregnancy, the mean
      concentration of oestradiol was significantly reduced in the treated cycle. As
      oestradiol stimulates both the development of uterine oxytocin receptors and the
      secretion of PGF2 alpha we suggest that any improvement in pregnancy rate after
      buserelin is due to a weakened luteolytic mechanism, resulting from a lower
      plasma oestradiol concentration.

PMID- 1343967
TI  - Regulation of steroidogenesis in the bovine placenta.
AB  - As pregnancy progresses in the cow, the secretory activity of the corpus luteum
      is markedly diminished. This reduced secretion is due to a decline in the number
      of viable luteal cells as well as reduction in the secretory activity and
      responsiveness of the cells to trophic agents. The principal extra-ovarian source
      of progesterone (P4) by mid-gestation therefore appears to be the placenta.
      Uniquely this P4 biosynthesis is cyclic-nucleotide independent, but the Ca+2
      dependent. It therefore appears that the Ca+2 second messenger and protein kinase
      C systems are responsible for regulation of sterol biosynthesis in the cow
      placenta. Dispersed bovine caruncle cells from the first trimester of pregnancy
      in comparison to caruncle cells of older than 90 days of gestation produce little
      P4 and are refractory to agents which enhance placental steroidogenesis. In order
      to explain this refractoriness of the first trimester cells, we determine (1) the
      expression of P450scc and its mRNA and (2) the expression of adrenodoxin. It was
      found that P4 synthesis by bovine maternal caruncle cells was low or undetectable
      in the first trimester but increased more than 10-fold in the second trimester of
      gestation. Addition of 25-OH-cholesterol to second trimester maternal cells
      increased P5 production but no effect was observed in first trimester cells.
      Cytochrome P450scc and its mRNA and adrenodoxin content were determined using
      Western blot or dot-blot techniques. Both proteins and the mRNA were detected in
      maternal tissue of first and second trimesters of gestation. In conclusion low P4
      levels synthesized by first trimester maternal cells are not due to the absence
      of either cytochrome P450scc or adrenodoxin protein or production of P450scc
      mRNA. The data suggest that the refractoriness of the maternal caruncle cells
      during the first trimester is the result of post-translational regulation.

PMID- 1343968
TI  - Maternal behavior and neuroendocrine regulation of suckling-mediated anovulation
      in cows.
AB  - Although it is clear that the initial endocrine deficit contributing to the
      length of the postpartum anovulatory period in suckled cows is of pituitary
      origin, this limitation is only operative for about the first 2 weeks of the
      puerperium. Thereafter, the pattern of LH secretion required for the final stages
      of follicular development and ovulation is blocked or attenuated through a more
      centrally regulated phenomenon. Hence, much of the recently published work in
      this area has focused on regulatory processes within the hypothalamus. This focus
      ignores the critical issue of exteroceptive signalling. Recent observations in
      this laboratory suggest that exteroceptive cues responsible for suckling-mediated
      anovulation are specifically attributable to the dams' own calf, but are not teat
      specific. In fact, suckling does not produce an extended anovulatory state in the
      absence of a maternal-offspring bond. This review provides an historical
      perspective of investigations leading to this conclusion, and proposes a
      conceptual working model that links the special senses, maternal behavior and
      neuroendocrine centers that drive gonadotropin secretion during the puerperium.

PMID- 1343969
TI  - Nutrition-endocrine interrelationships in the lactating and weaned sow.
AB  - Previous studies had identified the effects of nutrient restriction on delayed
      occurrence of estrus when body condition is low at farrowing or levels of intake
      fall below 2.5 kg (8.35 Mcal ME/h/d) during lactation. It appears that the
      failure via the GnRH pulse generator to stimulate sufficient LH pulsatility to
      trigger steroidogenesis may play a major role in the lack of reinitiation of
      cyclicity. Base-line concentrations, because of their variability between
      individual animals, may not be a major factor in predicting the time to return to
      estrus. Prolactin appears to be definitely antigonadotropic during lactation but
      may be involved in folliculogenesis effects during the postweaning period.
      Previous results would indicate that metabolic factors in concert with the major
      reproductive hormones play a key role in reestablishing the cycle postweaning. To
      achieve a greater understanding of the complexities of these two systems-
      nutrition and reproduction-greater emphasis must be placed on more precisely
      regulating the integral factors modulating the return to cyclic behavior.

PMID- 1343970
TI  - Metabolic and reproductive hormones during lactation and the post-weaning period
      in sows.
AB  - There is a great variation in body weight loss during lactation among primiparous
      sows fed a standard diet that is adjusted based on the number of piglets nursed
      and the maintenance requirements. Energy and protein catabolism is more
      pronounced during the first 1 to 3 weeks of lactation and sows with low weight
      loss recover earlier from their negative energy balance during lactation than
      sows with high weight loss. Using continuous blood collection a decrease in
      plasma levels of oxytocin, prolactin, and insulin, and an increase in plasma
      levels and no of LH pulses during lactation were demonstrated. Prolactin levels
      gradually increased in response to each suckling while only 40-50% of recorded
      sucklings induced a significant rise in plasma oxytocin. Following a 24-h fast
      during lactation, levels of prolactin were very low but increased rapidly after
      refeeding. Even plasma levels of insulin and glucose decreased to very low levels
      during fasting, but the release of LH was similar before and after refeeding.
      Weaning resulted in decrease in plasma levels of prolactin and increase in plasma
      levels and no. of LH pulses. Plasma levels of cortisol showed a diurnal pattern
      of change which disappeared on the day of weaning. In response to weaning plasma
      levels of glucagon and gastrin decreased, whereas insulin and somatostatin
      increased. At weaning sows with low weight loss during lactation had higher
      plasma insulin and lower plasma cortisol levels than sows with high weight loss,
      but no differences in levels or no. of LH pulses were observed between the two
      groups of sows.

PMID- 1343971
TI  - Ontogeny of gonadotropin action in the rat ovary.
AB  - Specific binding of radiolabelled FSH and LH to rat ovaries was demonstrated at
      the age of 7 days. However, when the biological response to LH and FSH was
      monitored by cAMP production in vitro, the FSH response appeared earlier than
      that of LH, on days 4 and 7, respectively. Cholera toxin stimulated cAMP
      production even in fetal ovaries, suggesting the presence of functional post
      receptor machinery of cAMP production. Hence, the appearance of the functional
      gonadotropin receptor probably plays a key role in the onset of postnatal ovarian
      steroidogenesis. To test the effect of gonadotropin suppression during postnatal
      ovarian development, a potent GnRH antagonist was administered to neonatal
      animals between days 1-6 or 1-9 of life. The ovarian responsiveness to FSH
      developed even in the absence of normal gonadotropin levels, but that to LH was
      suppressed after the longer antagonist treatment. The temporal relationship
      between the onset of LHR gene expression, i.e. transcription, and translation to
      functional receptor protein was thereafter investigated using the reverse
      transcriptase-polymerase chain reaction (RT-PCR) technique. The measurements
      revealed the existence only of truncated versions of LHR mRNA in the fetal ovary
      from day 17 of gestation up to day 7 of postnatal life. With the onset of the
      receptor function around day 7, also larger mRNA transcripts, corresponding to
      the full-length receptor protein appeared. Our findings suggest that the LHR gene
      may be constitutively expressed in the ovary and a change in the alternative
      splicing pattern may cause the onset of translation of a functional receptor
      protein.

PMID- 1343972
TI  - Advances in reproductive endocrinology of fish.
AB  - In teleosts two gonadotropins (GtHs) are produced: GtH I which stimulates
      steroidogenesis and incorporation of vitellogenin into the oocytes and GtH II,
      which stimulates steroidogenesis in the last stage of maturation and ovulation.
      Synthesis and release of GtHs are under control of gonadotropin releasing
      hormones, growth hormone, gonadotropin releasing inhibitory factor (GRIF)-
      dopamine, neuropeptide Y (NPY) gamma-aminobutyric acid (GABA) and melatonin. It
      was also found that calcium ions play a role of an intracellular mediator in GtH
      release. In ovaries, GtH stimulates production of 17 alpha-hydroxyprogesterone in
      the thecal cells. This steroid is transferred to granulosa cells where it is
      converted to 17 alpha 20 beta dihydroxy-4-pregnen-3-one (17 alpha 20 beta DHP).
      This steroid acts on the oocyte surface causing an appearance cytoplasmatic
      maturation promoting factor (MPF) which initiates the nuclear membrane breakdown
      and a subsequent cell division in both mitosis and meiosis. Teleosts are the only
      animals in which it is possible to change sex and to have population of fish of
      one sex. This possibility is widely applied in fisheries practice.

PMID- 1343973
TI  - Extragonadal gonadotropin receptors, their distribution and function.
AB  - Luteinizing hormone (LH) and a second pituitary gonadotropin, follicle
      stimulating hormone (FSH), together control steroid secretion and gamete
      development in both males and females. LH and its agonist human chorionic
      gonadotropin (hCG), share a common receptor in gonadal cells. There is increasing
      evidence for the existence of extraovarian LH/hCG binding sites in mammalian
      females. High affinity, low capacity LH/hCG receptors have been detected in pigs,
      rabbits and rats. Gonadotropin receptors in the human uterus were also
      demonstrated using immunocytochemical techniques. The presence of LH/hCG
      receptors, both in the endometrium and myometrium, has been so far found in pigs
      and humans. Receptors in the endometrium are present in glandular and luminal
      epithelium and stromal cells. In the myometrium, they are present in circular and
      longitudinal myometrial smooth muscle and vascular smooth muscle. Recently,
      LH/hCG receptor gene expression was confirmed both in the endometrium and
      myometrium of the pig. The amount of receptors is higher in the luteal phase as
      compared to the follicular phase of the estrous cycle indicating possible
      regulation of these receptors by ovarian hormones. Treatment with estradiol
      benzoate increased the number of LH/hCG binding sites compared with
      ovariectomized gilts receiving corn oil. However, administration of progesterone
      caused an elevation of these receptors, when compared with estradiol. Combined
      administration of estradiol and progesterone increased receptor capacity similar
      to progesterone alone. It seems that there are species differences in the uterine
      binding response to estradiol since the positive response to estradiol by uterine
      receptors in the ovariectomized pig is quite different from that observed in
      rabbits and rats. In the endometrium, hCG and/or LH may regulate glandular and
      luminal epithelial cell function via cAMP modulation or by increasing the local
      synthesis of steroid hormones. Stimulation of LH receptors with hCG in estrogen
      primed ovariectomized gilts had a quiescent effect on myometrial contractility in
      vitro. We examined also the effect of hCG on electromyographic activities of the
      uterus in ovariectomized and estrogen treated pigs. The hCG treatment caused a
      significant reduction of total duration of electrical activity and mean burst
      duration. Based on our earlier and recent results we suggest that the role of
      LH/hCG receptors in the myometrium is the regulation of uterine contractility,
      though the second messenger system remains to be elucidated.

PMID- 1343975
TI  - Hormonal regulation of ovarian function in vivo and in vitro.
AB  - In the ovary steroids are produced by the follicles, corpora lutea and
      interstitial cells. In the follicle a substantial steroid production starts after
      the antrum formation and the main steroid produced is estradiol which supports
      folliculogenesis. Its content rises as the follicle grows. In the preovulatory
      period of time estradiol, released in a great amount into the circulation,
      triggers the ovulation inducing discharge of LH from the pituitary gland.
      Afterwards the follicle stops producing estradiol and androgens and starts to
      form progesterone. Such a swish in steroid synthesis is a universal feature for
      many species investigated. The results of experiments suggest that this swish is
      due to the inhibition of androgen production and a subsequent decline of
      aromatase activity. After ovulation progesterone synthesis is continued by corpus
      luteum (CL). The pattern of steroids produced by CL depends upon the stage of
      luteal phase and upon the species investigated. In the pig newly formed CL
      contain little steroids. The highest progesterone and androgen content is
      characteristic for mature and midway CL. In regressing CL progesterone and
      androgen concentrations drop while estradiol reaches its highest level. Steroid
      synthesis is modulated by gonadotropins and steroids.

PMID- 1343974
TI  - New pathways in animal reproductive physiology frontiers and perspectives.
AB  - With the inrush of new data the recent clear division of neural, hormonal and
      immunological regulation has been seriously complicated. Both central and
      peripheral neural tissue produce over 30 neuropeptides, among which are many
      classic peptide hormones. A steroid biosynthetic pathway has been demonstrated in
      oligodendrocytes. However, the distribution and role of peptydoergic neurons
      within the reproductive system are only superficially known among farm animals.
      Neurons have receptors for many hormones and interleukins. Cells of the immune
      system, in addition to secretion of many interleukins and interferons, produce
      neuropeptides locally and they possess specific receptors for them as well. Till
      now, the interaction between the nervous, hormonal and immunological systems has
      not been taken into account while investigating the functions of ovarian
      follicles, the corpus luteum, oviduct and uterus. The penetration of blood and
      lymphatic vessels by hormones, neuropeptides and cytokins has not been taken into
      consideration also. The counter current transfer of many steroid and peptide
      hormones from ovarian venous and lymphatic effluent to arterial blood supplying
      the ovary and through arterial anastomoses of the oviduct and uterus has been
      hithero shown. It has been demonstrated that thanks to this system, arterial
      blood supplying the uterus and oviduct has, in physiological conditions, a much
      higher level of some steroid hormones such as progesterone and androstendione,
      37% and 36% respectively, than in systemic blood. Recently, a powerful exchange
      system for resupplying hormones to the brain which is dependent on the phase of
      the estrous cycle, has been discovered. It has also been demonstrated that
      neuropeptides LH-RH, beta-endorphin and oxytocin as well as the steroid hormone
      progesterone, were counter current transferred from venous to arterial blood at
      the perihypophyseal cavernous sinus and carotid rete in sheep and gilts, but only
      during specific periods of reproductive activity. The mechanism of this process
      is still unknown. The role of peptydoergic neurons and cytokins in vascular
      permeability during hormone counter current transfer in the broad ligament
      vasculature, perihypophyseal cavernous sinus and carotid rete has not been
      investigated. It is suggested that progress in this area may change our point of
      view on many basic regulatory mechanisms involved in animal reproductive
      physiology.

PMID- 1343976
TI  - Biogenic amines and the activity of the hypothalamo-pituitary-ovarian axis in
      ewes.
AB  - An important feature of communication between the central nervous system and the
      pituitary-ovarian axis is the pattern of pulsatile discharge of hypothalamic
      luteinizing hormone releasing hormone (LHRH). The discharge of LHRH is under
      control of noradrenergic, dopaminergic, and serotoninergic systems of the brain.
      These systems intervene between external and internal signals (e.g. photoperiod
      and gonadal steroids) and LHRH output. In the ewe, noradrenaline, dopamine and
      serotonin of the brain are implicated in the control of LHRH output, and hence
      luteinizing hormone (LH) release, during both the anoestrous and breeding
      seasons. These amines are involved in steroid-dependent and steroid-independent
      regulation of LHRH/LH discharge. An interplay of inhibitory versus excitatory
      influences of these amines on LHRH/LH release appears to govern the pattern of
      LHRH/LH output during the annual reproductive cycle and the ovulatory cycle. A
      concise overview of this topic will be provided.

PMID- 1343977
TI  - Control of the LH surge mechanism in the female pig.
AB  - The functionality of the oestrogen-positive feedback mechanism is the basis for
      the preovulatory LH surge and thus for regular cyclic activity in the sow. The LH
      surge mechanism (LH SM) gradually matures as a function of age, immature gilts
      display delayed, low amplitude LH surges in response to oestradiol benzoate (OB).
      The maturation of the LH SM apparently is ovarian oestrogen-dependent. Continuous
      ovarian secretions, probably oestrogens, also appear to be necessary for the
      final peripubertal maturation of the LH SM and to maintain the functionality of
      this mechanism in the sexually mature gilt. Superphysiological levels of
      oestrogens are, however, detrimental to the development of the LH SM. Failure of
      various infusions of the opioid antagonist naloxone during the surge period to
      enhance the magnitude of OB-induced LH surges in immature gilts does not support
      the idea, that central opioidergic systems are of major importance in preventing
      mature LH surge response at this age. However, opioids could be involved in the
      termination of the LH surge. Experiments using the opioid agonist morphine and
      the antagonist naloxone to demonstrate that opioids are involved in the
      generation of the LH surge in the mature gilt have so far provided equivocal
      data. Studies using pulsatile infusions of LHRH or of a potent LHRH-agonist
      during the surge period in OB-treated immature gilts, in which endogenous LHRH
      release was blocked by methallibure, suggest that oestradiol fails to generate
      mature LH surges because the gonadotrophs of the immature gilt are unable to
      respond to enhanced LHRH secretion during the surge period in an adult-like
      manner. During early lactation the LH SM cannot be activated by OB, while during
      late lactation a partial recovery of the LH SM occurs. Minor breed differences
      exist in the functionality of the LH SM during lactation between LW sows and
      highly fertile Chinese Meishan sows, in which lactational anoestrus is not
      obligatory.

PMID- 1343978
TI  - Central nervous system peptide and amino acid modulation of luteinizing hormone
      and prolactin secretion in the pig.
AB  - We recently demonstrated that pulsatile LH secretion is associated with pulsatile
      gonadotropin releasing hormone (GnRH) in the pig. Endogenous opioid peptide (EOP)
      inhibition of pulsatile LH and prolactin (PRL) secretion is dependent on
      reproductive status and development of this EOP system is a brain maturational
      process independent of the ovary. Once sexual maturation has occurred, EOP then
      become part of a progesterone dependent system and EOP inhibit a noradrenergic
      component of this system. During lactation, EOP also inhibit pulsatile LH, but
      stimulate PRL secretion. N-methyl-d,l-aspartate (NMA), an agonist of the
      excitatory amino acids (EAA), aspartate and glutamate, suppressed LH secretion in
      gilts pretreated with progesterone or vehicle. Both the EOP agonist, morphine
      (MOR), and the EOP antagonist, naloxone (NAL), delayed emergence and time to
      maximum serum LH concentration of the estradiol-induced LH surge in prepuberal
      and mature gilts, respectively. Therefore, EOP may normally have both a
      permissive as well as an inhibitory role in the LH surge mechanism. Although a
      norepinephrine synthesis inhibitor failed to alter basal PRL secretion, the PRL
      increase after NAL was suppressed in progesterone-treated ovariectomized (OVX)
      gilts. NAL suppressed the PRL response to NMA in OVX gilts pretreated with oil
      vehicle or progesterone, indicating that NMA stimulation of PRL secretion is
      mediated through the EOP system.

PMID- 1343979
TI  - [The role of the pineal gland in cartesian psychophysiological doctrine].
AB  - In the present paper, we review the cartesian description of the neuromuscular
      reflex and the sensorial perception as well as the hypothetical role of the
      pineal gland on these functions. We analyze the historical bases which support
      the physiological cartesian doctrine and, from the perspective of our present
      knowledge, we evaluate the contributions of Descartes to the scientific progress
      of his time. In the elaborated psychophysiological theory of the french wise, the
      pineal gland plays a pivotal role, raising the theory that the human soul could
      be located within this organ.

PMID- 1343980
TI  - Prenatal nicotine exposure induces cardiac adrenergic subsensitivity in adult
      rats.
AB  - Adult offsprings of Wistar female rats treated during pregnancy (days 1-20) with
      nicotine (1 mg/kg s.c.,b.i.d.), were tested in order to detect possible
      alterations in the reactivity of the cardiovascular system to sympathetic
      agonists. Dose-response curves to the pressor response of noradrenaline (NA) did
      not show any differences between control and experimental animals. However,
      cumulative dose-response curves to the chronotropic effect of NA on isolated
      atria were significantly shifted to the right in nicotine prenatal treated rats
      than in controls. Accordingly, 3H-dihydroalprenolol binding was significantly
      reduced in hearts of experimental animals as compared with controls, without any
      change in affinity. These data demonstrate long lasting deleterious effects
      induced by prenatal nicotine exposure, probably resulting from alterations in the
      sympathetic system during the developing stage.

PMID- 1343981
TI  - High-protein diet: effect on insulin secretion patterns from streptozotocin
      diabetic rats and mice.
AB  - In the present study we have investigated the effect of a high-protein feeding on
      glucose induced-insulin secretion patterns from high dose streptozotocin (SZ)
      injected rats and mice, and from mice given multiple low doses of SZ. For this
      purpose male rats and mice were fed either a high-protein, carbohydrate-free
      diet, or control diets, before and after i.p. injections of SZ, or citrate buffer
      only. Our results show that when SZ was given as a single diabetogenic dose, rats
      and mice kept on the high-protein diet presented lower serum glucose levels,
      normal basal insulin values, and higher first and second phases of stimulated
      insulin release, when compared with diabetic animals on control diets.
      Furthermore, when rats prolonged their high-protein feeding from 4 to 11 days
      after SZ injection, there was an additional increment in insulin secretory
      capacity with a further diminution in serum glucose levels. We also show that
      high-protein feeding in mice given multiple low doses of SZ (a model of
      autoimmune diabetes), produced a diminution in serum glucose values, and an
      improvement in both phases of stimulated insulin release. Thus, in the two models
      of experimental diabetes used here, high-protein feeding exerts beneficial
      effects in beta cell responsiveness to glucose.

PMID- 1343983
TI  - [Coronary surgery and its alternatives. Introductive essay].

PMID- 1343982
TI  - Cyclic AMP infusion and blood sugar, serum insulin and serum nonesterified fatty
      acid responses to glucose in recent experimental hyperthyroid dogs.
AB  - Recent experimental hyperthyroid (REH) dogs exhibit poor "in vivo" insulin
      responses to glucose probably due to a failure somewhere in cAMP-adenylate
      cyclase system. The actions of exogenous cAMP on these responses and on the
      regulation of blood sugar (BS) and serum nonesterified fatty acids (NEFA) during
      glucose infusion tests (GIT) in REH and normal dogs were studied here.
      Hyperthyroidism was induced by 1-thyroxine administration (100 micrograms/kg body
      wt./die, 10 days). GIT consisted of i.v. glucose-priming followed by glucose i.v.
      continuous infusion (60 min). cAMP (0, 33 or 66 mg/kg body wt./min) was infused
      alone (30 min) and then overlapped to gluco-se infusion (60 min). Peripheral
      veins were used for infusions and blood sample withdrawal. BS, serum
      inmunoreactive insulin (IRI) and serum NEFA concentrations, basally and
      throughout the test, were measured. Basally, there was neither action nor
      interaction of hyperthyroidism and exogenous cAMP on these variables. During the
      GIT, the BS levels remained unaffected by hyperthyroidism; cAMP increased them,
      but failed to interact with hyperthyroidism. cAMP noninfused normal dogs
      responded to hyperglycemia with hyperinsulinemia, whereas REH dogs noninfused the
      nucleotide did not. cAMP administration at a high dose promoted their response in
      normal and REH dogs, particularly in the former; in the latter, the response was
      still lower than in cAMP noninfused normal controls. Although recent
      hyperthyroidism increased serum NEFA basal level, it exerted neither action nor
      interaction with the infused cAMP on serum NEFA during GIT. Results are discussed
      on the basis that the abolished insulin secretion "in vivo" characterizing the
      REH dogs, related to beta-adrenergic deficiency, can be for the most part
      restored by exogenous cAMP administration, despite which some glucose and
      triglyceride metabolism impairments are developed.

PMID- 1343984
TI  - [Emergency aorto-coronary bypass after myocardial infarction].
AB  - During a recent three-year period, 37 patients had an emergent aortocoronary
      bypass (ACB) after evolutive acute myocardial infarction. The patients are
      divided up into two groups: group I includes 12 patients who were operated after
      the failure of early thrombolysis; group II includes 25 patients operated after
      the failure of revascularization through percutaneous angioplasty. In group I,
      all patients survived and 9 had no postoperative complications. In group II, the
      outcome was favorable for 16 patients. Long-lasting postoperative inotropic
      support was required for nine patients. Two patients died early. In all patients
      of the study, surgery failed to prevent myocardial necrosis but there was no
      recurrence of angina nor major left ventricular malfunction in the long term.
      This work suggests that early surgery after acute myocardial infarction may be a
      rescue procedure, with low risks and good long-term results.

PMID- 1343985
TI  - [Results of coronary artery bypass in patients with altered left ventricular
      function].

PMID- 1343987
TI  - [Recurrence of cervical lymph node involvement in surgically treated thyroid
      cancer. Uselessness of routine cervical lymph node excision (medullary carcinoma
      excluded)].
AB  - From 1966 throughout September 1990, 753 patients underwent surgery for thyroid
      carcinoma, in the same institution, covering all pathological types. Complete
      follow-up was achieved in 96% of them, being at least 7 years in 50% of cases.
      599 (80%) are currently alive. Neck dissection was not routinely done, except for
      medullary thyroid carcinoma, but rather selectively, if nodes were palpable
      either pre or intraoperatively, and also (since oct. 1983 i.e. the last 400
      cases) if, after routine sampling of mid jugular nodes, frozen sections assessed
      nodal invasion. On the grounds of this policy, 205 patients underwent unilateral
      or bilateral neck dissection; 17% of them died during follow-up whereas 5.9% (12
      cases) exhibited a cervical nodal recurrence, 6 of them occurring less than two
      years post-operatively, including 3 medullary thyroid carcinomas. 548 had no neck
      dissection; 9% died during follow-up whereas 0.9% (5 cases) exhibited a cervical
      nodal recurrence, 3 of them occurring less than two years post-operatively.
      Routine neck dissection seems not to be justified in the surgery of non medullary
      differentiated thyroid carcinoma, in as much as late occurrence of cervical node
      metastases is uncommon and does not obviously impair life-expectancy.

PMID- 1343986
TI  - [Can pheochromocytoma be considered a benign unilateral intra-adrenal sporadic
      hypertensive tumor ? Reflections on a series of 105 surgically treated
      subdiaphragmatic chromaffin tumors].
AB  - In a 20 year period, from 1971 through 1991, 105 chromaffin tumours--excluding
      cervical ones--were operated by the same surgeon: 50 during the first 15 years
      and 55 during the last 5 years. Pheochromocytomas are defined as intra-adrenal
      chromaffin tumours, and paragangliomas--or ectopic pheochromocytomas--as of extra
      adrenal location. Among those tumours, 30 were malignant (i.e. metastatic) and 75
      benign. Among the 30 malignant tumours, 14 were ectopic, 2 occurred in a MEN II A
      setting and were bilateral, 2 were associated with liver adenoma and liver
      hemangioma respectively suggesting Von Hippel-Lindau syndrome, and one case was
      associated with a seemingly sporadic primary hyperparathyroidism. 9 out of those
      30 malignancies were not associated with hypertension. Among 75 benign
      pheochromocytomas or paragangliomas, 10 were ectopic, 7 occurred in a MEN setting
      (6 type II, 1 type I). 3 patients without evidence of MEN or other
      neuroectodermal abnormalities presented bilateral pheochromocytoma, either
      synchronous (2) or metachronous (1). 7 cases occurred in a Von Hippel-Lindau
      syndrome (3 bilateral) and 4 in a neurofibromatosis setting (1 bilateral). 3
      other cases were familial without evidence of MEN (including a case of triple
      tumour: bilateral and ectopic and another ectopic case). 2 other cases were
      associated with seemingly sporadic hyperparathyroidism. As a whole, in 34 of 75
      benign pheochromocytomas or paragangliomas, the tumour was not intra-adrenal,
      unilateral and sporadic. Among those 75 tumours, 22 were not overtly
      hypertensive, including 10 out of the 41 seemingly intra-adrenal, solitary and
      sporadic. The pheochromocytoma, benign, intra-adrenal sporadic, hypertensive
      accounts for no more than 30% of the subphrenic catecholamine-secretin chromaffin
      tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1343988
TI  - [Diagnostic laparoscopy. Its current indications].
AB  - Operative laparoscopy and laparoscopic surgery are quite topical today, but not
      so much diagnostic laparoscopy. In fact, the wide distribution and great accuracy
      of new noninvasive exploratory techniques has revolutionized strategy for the
      diagnosis of abdominal diseases. It has been said that these techniques have now
      superseded laparoscopy, which should be abandoned. The reply should be that,
      indeed, laparoscopy has lost many of its classic indications, but that it still
      retains other important ones. The results obtained with a very close integration
      of laparoscopy and ultrasonography should particularly be emphasized, as they
      provide a decrease in risks and an improvement of diagnoses.

PMID- 1343989
TI  - [What is the role of elective surgery in diverticular sigmoiditis?].
AB  - From 1981 to 1991 inclusive, 188 operations were carried out for diverticular
      sigmoiditis. One hundred and thirty-nine patients were operated in emergency for
      acute complications (123) or fistulae (16), and another 49 had surgery scheduled
      outside acute crisis periods. Mortality and morbidity respectively are 16.5 and
      31% in the first group, against 0 and 12% in the second one. Similarly, the stay
      in hospital varies from 13 days for scheduled surgery to 23 days for emergent
      surgery, the latter also requiring to account for risks and for the duration of a
      second operation that is far from exceptional (40%). Considering the severity of
      some evolutive complications, the authors advocate early radical surgery for
      symptomatic diverticular sigmoiditis, after the second crisis or as soon as the
      first one if it has been severe, and in young subjects and patients at risks.

PMID- 1343990
TI  - [Cervical osteoid osteoma. Report of a case and review of the literature].
AB  - One case of a cervical osteoid osteoma is presented and compared with infrequent
      similar cases from the literature. The authors recall the diagnosis difficulties,
      facing a long standing not explained neck pain due to poor neurological and
      current radiological informations. The interest of the bone scintigraphy, CT scan
      and M.R.I. are emphasized. Like in other cases, the pain disappeared after
      surgical removal of the tumor. The eventually associated scoliosis often rectify
      too.

PMID- 1343991
TI  - [Pancreatic metastasis of naso-sinusal epithelioma. Apropos of a case].
AB  - The authors report a pancreatic metastasis of sinusal squamous cell carcinoma in
      a 69 year-old man, 18 years after the first excision of the primary neoplasm. The
      metastases appearing in a patients having previously presented several tumors,
      was detected by a rising CA 19-9 level and a pancreas head enlargement at the CT.
      The diagnosis was identified at laparotomy by tumor biopsy. The vascular
      involvement of the tumor obliged to perform double bypass. 103 cases of
      pancreatic metastases, published in the literature from 1983 to 1991, are
      reviewed. Generally the pancreatic mass is visualized by CT but the diagnosis is
      only carried out on microscopy. Treatment depends on anatomical and pathological
      characteristics of primary and secondary tumours. Solitary metastasis of renal
      carcinoma origin have the best prognosis after radical surgery. In other cases
      palliative procedures are widely used. First case of pancreatic metastasis
      originated from recurrent sinusal squamous cell carcinoma with poly-tumoral
      clinical presentation.

PMID- 1343992
TI  - [Arteriovenous fistula for chronic hemodialysis. 370 patients].
AB  - In cases of chronic renal failure, the usual technique for vascular approach is
      an arteriovenous fistula (AVF). This is the vascular approach with the longest
      lifetime. Microsurgery has improved the realization technique. This technique was
      used between 1978 and 1987 in 370 adult patients. Distal AVFs are made as a
      priority to preserve the patient's vascular capital. Radial AVF is the basic
      technique. Complications, including thrombosis, aneurysms, stenosis, low flow
      rate, require second surgery that must often be repeated. Arteriovenous bypass
      with a saphenous or cubital venous graft is used in difficult cases. Bovine
      carotid artery grafts are still used as bypass grafts in occasional cases; their
      lifetime is usually short. Catheterization through a jugular (never subclavian)
      site is a temporary alternative.

PMID- 1343993
TI  - [Eventration and inguinal hernia. Myoplasty using the Musculus gracilis].

PMID- 1343994
TI  - Effect of using soft liner on bone density around the abutments supporting
      complete lower overdenture.
AB  - The effect of lower acrylic overdentures lined with soft liner on bone density
      around the abutment was studied on 14 patients divided into two equal groups.
      Group I patients using lower acrylic overdenture lined with soft liner. The
      abutments selected in each patient were two canines and two posterior. Bone
      density was measured from periapical radiographs made at denture insertion and
      after one year of denture use, for each abutments, using an accurate
      densitometer. The results showed decrease in bone density in the crestal alveolar
      bone around the abutments through the one year study period. patient using
      superstructure lined with soft liner showed less bone density than those using
      acrylic overdenture. The results of these study reached the conclusion that the
      resiliency of soft liner reduces the load applied over the overdenture abutments
      and in turn reduces alveolar bone changes.

PMID- 1343996
TI  - Durability of cermet ionomer cement conditioned in different media.
AB  - The glass ionomer cement has exhibited significant adhesion to hard tooth
      structures, and good cariostatic properties. The sintering of the silver alloy
      powder and glass ionomer cement "cermet cement" has provided additional
      improvement in the physical properties of the restorative material. These were
      flexural resistance, wear resistance, increased radio-opacity, hardness and
      porosity. The improvement in the physical properties of the cermet glass cements
      has provided an extension in their clinical use as core build up, lining for
      inlays, amalgam and composite restoratives, fissure filling, restoration of
      primary teeth, class II tunnel preparation, treatment of root caries and repair
      of defective metal margins in crown and inlays.

PMID- 1343995
TI  - Comparative study of ultrastructural changes of the gingival hyperplasia induced
      by cyclosporine and dilantin.

PMID- 1343997
TI  - Vibration pattern of different endosonic instruments.
AB  - The history of using ultrasound in dentistry goes back to 1952. The first report
      on the use of ultrasound as an adjunct to mechanical debridement was given by
      Richman in 1957. It's popularity started with the work of Martin then many
      clinical evaluations were reported mainly discussing the efficiency of
      ultrasonics in root canal preparation.

PMID- 1343998
TI  - Histochemical classification of human minor labial salivary glands according to
      their glycoprotein content.
AB  - There is debate about the nature of the secretory cells in human labial salivary
      glands. Histologically two types of acinar cells were observed. The predominant
      mucous acini, few basophilic serous acinar cells were detected. Histochemical
      differentiation of these cells according to their neutral and acidic
      mucopolysaccharides content using PAS, AB pH 1 and AB pH 2.5 stain revealed the
      presence of three types of acinar cells: 1. Cells rich in both neutral and acidic
      mucopolysaccharides. 2. Cells rich in either neutral or acidic
      mucopolysaccharides. 3. Cells contain neither neutral nor acidic
      mucopolysaccharides. The first type constitute the major component of the gland.

PMID- 1343999
TI  - Trimetaphosphatase activity in rat incisor odontoblasts during early
      dentinogenesis.
AB  - The ultrastructural localization of trimetaphosphatase activity have been
      investigated in early stages of dentinogenesis in the rat incisor. Extracellular
      reactive structures were present in between the odontoblasts during early
      secretion and absent later on. Tubular lysosomes were observed for the first time
      in odontoblasts and seemed to be involved with other elements of the lysosomal
      system in endocytosis of extracellular substances.

PMID- 1344000
TI  - Anti-inflammatory effect of natural steroid sapogenins on oral aphthous ulcers.
AB  - The search in plants for sapogenins has been stimulated by the need for readily
      accessible sources of sapogenins which can be converted in the laboratory to
      animal sterols of therapeutic importance. The present study represents a clinical
      trial for the investigation of the antiinflammatory effect of natural steroidal
      sapogenins on oral aphthous ulcers.

PMID- 1344001
TI  - Occlusal vertical dimension changes in visible light-cured resin.
AB  - On a twenty standard, identical edentulous upper and lower casts, an identical
      upper and lower waxed-up sets of dentures were constructed with same vertical
      dimension of occlusion. These waxed up dentures were divided into two equal
      groups. For group I, the dentures sets were processed in compression molding heat
      cured acrylic resin denture base material. For group II, the denture sets were
      processed in visible light-cured denture base material. After processing the
      vertical dimension of occlusion was measured for every denture set in both
      groups. It was found that there was an increase in the vertical dimension of
      occlusion on group I and a decrease in the vertical dimension of occlusion in
      group II. Regardless of the direction of the changes in the vertical dimension of
      occlusion, it was found that there was a significant difference between the
      dimensional changes in both groups and the dimensional changes in the denture
      bases of group I was more than group II by 54.5%.

PMID- 1344002
TI  - Examination services provided by dental hygienists.
AB  - The information presented in this paper was obtained as part of an ongoing
      longitudinal study of 1982 dental hygiene graduates. This paper presents
      information contracted by the American Dental Hygienists' Association and
      includes information on examination services provided to new and recall, child
      and adult dental hygiene patients by dental hygienists. Mail questionnaires were
      sent to a cohort of 1,008 dental hygienists who graduated in 1982. Data presented
      here were collected in September 1986. Surveys were returned from 766 subjects,
      77% of those with valid addresses. Of the respondents, 455 were working in
      traditional clinical dental hygiene positions and provided information on patient
      examination services. The frequencies reported for the 15 examination services
      investigated by the dental hygienists varied for child and adult patients and for
      new and recall patients. Visual gingival examination was the most frequently
      provided service. In conclusion, dental hygienists need to incorporate additional
      patient examination services into their diagnostic workups to ensure adequate
      patient care and to provide adequate information to evaluate their dental hygiene
      care.

PMID- 1344003
TI  - Monitoring blood pressure; five minutes critical to quality patient care.

PMID- 1344004
TI  - So your patient is taking ... a calcium channel blocker (CCB)!

PMID- 1344005
TI  - Chemical and pharmacological studies on efficacy of Japanese and Chinese herbal
      medicines.

PMID- 1344006
TI  - A new neutralization method for influenza virus in cell culture.
AB  - A novel neutralization method (ELISA-NT) has been developed for simple detection
      of neutralizing antibodies to influenza virus in which type specific soluble (S)
      CF antigen produced by unneutralized virus was measured by anti-S immune (probe)
      serum and enzyme-labelled Clq. Neutralizing antibody activity was determined
      within 48 h and expressed as a new term, NT% of the quantity of neutralized
      virus. A good correlation was found between NT% determined by the ELISA-NT method
      and NT titer by the conventional method in 82 human serum samples (r = 0.941 for
      type A and r = 0.875 for type B of influenza virus, p < 0.01).

PMID- 1344007
TI  - Cytotoxic effects of antitumor agents on mouse tracheal organ cultures at
      ultrastructural level.
AB  - A cytotoxic effect of antitumor agents (mitomycin C;MMC, adriamycin;ADM,
      bleomycin;BLM, 5-fluorouracil;5-FU, and cisplatin;CDDP) on ciliated epithelial
      cells of mouse tracheal organ cultures was studied in transmission electron
      microscopy. Mouse tracheal rings incubated with each agent in a concentration of
      1 microgram/ml or 10 micrograms/ml were observed after 1, 2, and 20 hr of the
      incubation. After 2 hr, the ciliated epithelial with MMC or ADM of 1 microgram/ml
      exhibited appearance of lipid droplets in the nonciliated cells and the swelling
      of mitochondria and epithelial cells. Further incubation of 20 hr with those
      agents resulted in the pronounced degeneration including the ciliary subsidence
      into intracellular spaces, balloon-like ciliary swelling, and cellular
      destruction. Whereas, the ciliated epithelia with 5-Fu, BLM or CDDP did not show
      any notable change within 2 hr. After 20 hr, these exhibited the swelling of
      mitochondria, cilia and epithelial cells. The ciliated epithelia incubated with
      MMC or ADM of a greater concentration of 10 micrograms/ml showed remarkable
      cytotoxic effects after 1 hr of the incubation. The morphological changes in the
      epithelial cells with 1 hr incubation were almost similar to those of 20 hr
      incubation with the 1 microgram/ml. After 20 hr, the cellular degeneration
      proceeded to extremely flattened epithelial cells with disappearance of cilia and
      appearance of numerous vacuoles. Those with 5-FU, BLM or CDDP of 10 micrograms/ml
      exhibited ciliary swelling after 2 hr, but the morphological changes of 5-FU were
      more remarkable than those of BLM or CDDP. After 20 hr, the pronounced
      degeneration was observed, and it was similar to one of MMC or ADM of 2 hr
      incubation.

PMID- 1344008
TI  - Suppression of 125I-uptake in mouse thyroid by seaweed feeding: possible
      preventative effect of dietary seaweed on internal radiation injury of the
      thyroid by radioactive iodine.
AB  - We conducted an animal experiment to determine how dietary seaweeds rich in
      iodine and dietary fibers suppress radioactive iodine uptake by the thyroid,
      using mice and four kinds of experimental diets, three with 1% or 2% powdered
      fronds of the kelp Laminaria religiosa and 2% powdered laver Porphyra yezoensis,
      and one with cellulose. Iodine content of a hot-water extract of the kelp was
      0.530 +/- 0.001%, and its dietary fiber (DF) values were 52.8 +/- 1.2%. Iodine in
      an extract of the laver was 0.008 +/- 0.001%, and its DF values were 41.4% +/-
      0.7%. A statistically significant reduction of 125I uptake by the thyroid, 3
      hours after intragastric administration of the radionuclide at a dosage of 18.5
      kBq or 185 kBq in 0.3 ml aqueous solution per mouse, was observed in mice
      previously fed the experimental diets containing 1% and 2% kelp during periods
      varying from 24 hours to 7 days. The degree of the suppression was observed to
      depend on the amount of iodine in the diet or in the injected sample, no matter
      whether organic or inorganic, judging from the results of an additional
      experiment. Thus, we conclude that previously fed iodine-rich material,
      especially dietary seaweeds rich in iodine and other minerals, vitamins, and beta
      carotene, such as kelps or laver supplemented with inorganic iodine, may be
      effective in prevention of internal radiation injury of the thyroid.

PMID- 1344009
TI  - Oxygen-independent antimicrobial activity against Salmonella enteritidis of
      specially activated macrophage with living vaccine.
AB  - Characteristics of peritoneal macrophages recovered from mice infected with two
      attenuated strains SER and Jena of Salmonella enteritidis were compared. Strong
      resistance against lethal infection with a virulent strain 116-54 of S.
      enteritidis was seen in a group of mice immunized with strain SER, but not in a
      group of mice immunized with strain Jena as well as in a control group.
      Peritoneal macrophages from mice immunized with strain SER showed an enhanced
      Salmonella-killing activity, an increased generation of O2- and an increased
      expression of Ia antigen on 7 to 14 days after infection when compared with those
      from mice immunized with strain Jena and thioglycollate(TG)-elicited macrophages
      as a control. The bacterial number of strain Jena in organs decreased more
      rapidly than that of strain SER after day 4 of infection. These observations
      suggest that the survival of an attenuated Salmonella bacilli at reticulo
      endothelium is essential to increase of their activities of macrophages.
      Macrophages from mice injected with recombinant interferon(IFN)-gamma for 3 days
      induced the activated stage of the same characteristics as noted in activated
      macrophages from mice immunized with strain SER. Effect of oxygen intermediates
      (OI) scavengers such as superoxide dismutase and catalase on Salmonella-killing
      activity of activated macrophages was not seen at all. These results suggest that
      an increased generation of OI may be not primarily responsible for the ability to
      inhibit the intracellular growth of a virulent strain of S. enteritidis in
      macrophages activated by immunization with live, attenuated strains and injection
      with rIFN-gamma.

PMID- 1344010
TI  - Effect of short-term fasting treatment on liver and renal function.
AB  - Five healthy male adults were deprived of food for a short period (40 hr) and
      biochemical studies and urinalyses were done before and after fasting to
      determine the effects on liver and renal functions. Acceleration in lipid
      metabolism was seen with an increase of about 90% in NEFA and about 20% in TG.
      GOT, GPT and LDH showed elevations of about 40 to 100% indicating a slight effect
      of 40 hr fasting on liver functions. BUN, HDL-C and ALP showed increases of about
      30% while, CPK and TC showed decreases of about 20%. In the other parameters
      changes of about 10% were seen. After a fasting with water intake of about 1,000
      ml/day, a body weight loss of 1.2 kg was observed at 40 hr. During the short-term
      fasting (40 hr) as done in our study, changes were seen in glucose and lipid
      metabolism. However, since no abnormalities were seen in general biochemical
      parameters, we consider that a fasting of this duration is valuable for use as
      one of the fastings.

PMID- 1344011
TI  - Role of lipid peroxidation and antioxidants in aging process and thalassemia.
AB  - Oxygen free radicals and other oxygen derived species (Superoxide, O2-;
      Hydroperoxide, HOO; Singlet oxygen, 1O2-; Hydroxyl radical, OH; and Hydrogen
      peroxide, H2O2) including lipid peroxides have been suggested as important
      causative agents of aging and several human diseases, including cancer, multiple
      sclerosis, Parkinson's disease, autoimmune disease, ischemia, anemia, senile
      dementia, asbestosis and in thalassemia. This paper aims to communicate some of
      the theories and rationales in aging process and thalassemia.

PMID- 1344012
TI  - Accidents do not happen--they are caused.

PMID- 1344013
TI  - Comparative study of sevoflurane with other inhalation agents.

PMID- 1344014
TI  - What's new in local anesthesia?

PMID- 1344015
TI  - Techniques for induction of general anesthesia in the pediatric dental patient.

PMID- 1344016
TI  - Contemporary anesthetic techniques for orthognathic surgery.

PMID- 1344017
TI  - Diagnosis and treatment of respiratory problems in sedation and anesthesia for
      dentistry.

PMID- 1344018
TI  - Anesthetic management of the chemically dependent patient.

PMID- 1344019
TI  - Electronic dental anesthesia.

PMID- 1344020
TI  - Contemporary intravenous anesthetic agents and delivery systems: propofol.

PMID- 1344021
TI  - Approach to electrical anesthesia: nine years of experience in
      odontostomatological surgery.

PMID- 1344022
TI  - From the eye of the storm, with the eyes of a physician.

PMID- 1344023
TI  - The impact of the HIV epidemic on tuberculosis control programmes in developing
      countries.

PMID- 1344024
TI  - Physical characteristics of an enclosed afferent reservoir breathing system.
AB  - We have assessed the characteristics of the Ohmeda Enclosed Afferent Reservoir
      Breathing System (EAR) using simulated spontaneous ventilation and controlled
      ventilation. The additional work of breathing through the system was measured and
      shown to be comparable to that of a modified Mapleson D breathing system (Bain)
      for fresh gas flows producing similar end-tidal carbon dioxide concentrations. It
      was shown under conditions of simulated controlled ventilation that end-tidal gas
      concentration was relatively insensitive to variations in inspired to expired
      ratio (I: E), tidal volume (VT) and deadspace (VD). Measurement of the volume of
      carbon dioxide rebreathed using simulated spontaneous ventilation led to the
      prediction that rebreathing of carbon dioxide would begin to occur in the EAR
      when fresh gas flow to total ventilation ratio (VF: VE) was approximately 0.87.
      However, comparison of the results of model lung tests and clinical data suggests
      that great caution should be taken in extrapolating such results into clinical
      advice.

PMID- 1344025
TI  - Noninflammatory focal dermal elastolysis.

PMID- 1344026
TI  - Incommensurate oxygen consumption in response to maximal oxygen availability
      predicts postinjury multiple organ failure.
AB  - Untreated flow-dependent oxygen consumption (VO2) has recently been implicated as
      an unrecognized risk factor for multiple organ failure (MOF). We therefore
      prospectively studied 39 severely injured patients with known risk factors for
      multiple organ failure who were subjected to an established resuscitation
      protocol aimed at maximizing oxygen delivery (DO2 greater than 600 mL/min.m2) to
      attain a VO2 goal of greater than 150 mL/min.m2. Fifteen (38%) of these high risk
      patients did not meet this VO2 goal by 12 hours. These nonresponding patients had
      significantly elevated lactate levels, suggesting defective aerobic metabolism.
      Of note, this blunted VO2 response despite maximal efforts to enhance peripheral
      oxygen availability predicted MOF. These data serve to re-emphasize the
      importance of the initial shock insult in causing or priming the host for the
      development of late MOF.

PMID- 1344027
TI  - Antiglucocorticoid effects of DHEA-S in Alzheimer's disease.

PMID- 1344028
TI  - Empty sella resulting from the spontaneous resolution of a pituitary
      macroadenoma.
AB  - Recent studies suggest that the infarction of a pituitary adenoma may be a
      frequent cause of an empty sella turcica. However, to date, evidence of such
      progression has been largely speculative. We present the case of a patient with a
      pituitary macroadenoma that underwent spontaneous involution resulting in an
      empty sella, as documented by serial magnetic resonance imaging scans. A brief
      review of the proposed causes of primary empty sella, with emphasis on pituitary
      necrosis, is provided.

PMID- 1344029
TI  - Functional restoration. Pitfalls in evaluating efficacy.

PMID- 1344030
TI  - Use of an antibiotic-bonded graft for in situ reconstruction after prosthetic
      graft infections.
AB  - We have developed an infection resistant vascular prosthesis by bonding rifampin
      to Dacron grafts with the use of a collagen matrix release system. The purpose of
      this study was to determine the efficacy of this antibiotic-bonded graft in
      resisting infection after an in situ reconstruction of a previously infected
      prosthetic bypass. Eighty-three adult mongrel dogs underwent implantation of a 3
      cm untreated Dacron graft into the infrarenal aorta. This initial graft was
      deliberately infected, at the time of operation, with 10(2) organisms of
      Staphylococcus aureus by direct inoculation. One week later, the dogs were
      reexplored, the retroperitoneum debrided, and the animals randomized to undergo
      an end-to-end in situ graft replacement with either one of two types of
      prosthetic grafts: group I (collagen, n = 36) received control collagen
      impregnated knitted Dacron grafts; group II (rifampin, n = 47) received
      experimental collagen-rifampin-bonded Dacron grafts. Each group of animals was
      then subdivided to receive one of four treatment protocols: (a) no antibiotic
      therapy, (b) cephalosporin peritoneal irrigation solution (cefazolin 500 mg/1000
      ml) during operation and two doses of cephalosporin (cefazolin, 500 mg
      intramuscularly) postoperatively, (c) treatment as in protocol group b plus 1
      week of cephalosporin (cefazolin, 500 mg intramuscularly, twice daily), and (d)
      treatment as in protocol group b plus 2 weeks of cephalosporin (cefazolin, 500 mg
      intramuscularly, twice daily). All grafts were sterilely removed between 3 and 4
      weeks after implantation. There were no anastomotic disruptions and all grafts
      were patent at the time of removal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1344031
TI  - Coronary-prone behaviour pattern and myocardial infarction.
AB  - Seventy five patients with acute myocardial infarction (MI) and forty matched
      control subjects were assessed for coronary-prone behaviour pattern by a self
      administered scale. Analysis of the results showed a higher incidence (P < 0.001)
      of type A behaviour pattern in acute (MI) patients, as compared to controls.

PMID- 1344032
TI  - A case of human chimerism detected by unbalanced chromosomal translocation.
AB  - Chimerism in humans is usually found only because of discrepancies in unique
      blood group typing or sex chromosome complements. We describe a case found
      because of an inherited chromosomal translocation. A female carrier of the
      balanced reciprocal translocation t(14;20)(q31;q13.3) had a twin pregnancy. After
      birth the B-twin, a girl, was found to have the balanced translocation. The A
      twin, a severely malformed and stillborn boy, had two different karyotypes; a
      normal 46,XY and an unbalanced translocation derivative 46,XY,-14,
      +der(14)t(14;20)(q31;q13.3). He was a dispermic chimera, formed by two fertilized
      oocytes.

PMID- 1344033
TI  - Isoniazid induced peripheral neuropathy.

PMID- 1344034
TI  - Selenium, retinol, retinol-binding protein, and uric acid: from epidemiology to
      clinical prevention trials.

PMID- 1344035
TI  - Artists' offspring.

PMID- 1344036
TI  - Mimics of sarcoidosis. Granulomatous hypogammaglobulinaemia.

PMID- 1344037
TI  - Prognosis of sarcoidosis. An unresolved issue.
AB  - Prognosis of sarcoidosis may be difficult to establish because the disease may
      follow an unpredictable course. It depends mainly on the persistence of activity
      over time and on the type of organ involved and its degree of functional
      impairment. It would be very useful for clinicians to be able to identify at
      diagnosis which factors would predict the final outcome of the disease.
      Multivariate statistical models are proposed in order to study factors
      influencing the persistence of activity as one of the best methods of studying
      the prognosis of sarcoidosis.

PMID- 1344038
TI  - High resolution computed tomography in sarcoidosis and extrinsic allergic
      alveolitis: imaging insights.
AB  - Chest radiography gives a useful but imprecise indication of the extent of
      diffuse lung disease. The limitations in sensitivity and specificity of chest
      radiography in this context are well known and have been reinforced with the
      advent of computed tomography and its application to this difficult diagnostic
      area. High resolution computed tomography shows morphological detail invisible on
      chest radiography and both sensitivity and specificity in diffuse lung disease
      are greatly improved with this technique. Features of sarcoidosis and extrinsic
      allergic alveolitis revealed by high resolution computed tomography are examined
      in this review.

PMID- 1344039
TI  - Tumour necrosis factor production by alveolar macrophages in pulmonary
      sarcoidosis and tuberculosis.
AB  - Tumour Necrosis Factor alpha (TNF/Cachectin) is a cytokine produced mainly by
      macrophages, which has been shown to cause endothelial cell damage, pyrexia and
      weight loss, clinical features of tuberculosis, but not of sarcoidosis which is
      in many other respects a similar disease. 1,25 di-hydroxy Vitamin D and gamma
      interferon, factors which are present in vivo in both tuberculosis and
      sarcoidosis, enhance the ability of macrophages to release TNF in vitro. We have
      studied the ability of pulmonary alveolar macrophages (PAM) harvested by broncho
      alveolar lavage (BAL) to produce TNF in response to stimulation with E. coli
      endotoxin lipopolysaccharide (LPS). 25 patients undergoing bronchoscopy and BAL
      were studied: 9 with sarcoidosis, 7 with tuberculosis (TB) and 9 (non-neoplastic)
      disease controls. TNF was assayed by Enzyme Linked Immunosorbent Assay (ELISA) in
      lavage fluid and cell culture supernatants. No TNF was detected in lavage fluid
      from any of the groups. PAMs from control patients released no detectable TNF
      spontaneously, but released 59 +/- 31 units after LPS stimulation. Cells from
      patients with sarcoidosis and tuberculosis released TNF spontaneously in vitro
      (TB 226 +/- 106 units; Sarcoidosis 293 +/- 176). TNF release by these cells was
      not increased further by addition of an optimal concentration of LPS. Thus, the
      pulmonary macrophages of patients with sarcoidosis and tuberculosis released
      significantly more TNF than those of controls.

PMID- 1344040
TI  - Bronchopulmonary lavage (BAL). A window of the lungs.
AB  - Bronchopulmonary lavage (BAL) has provided a fresh dimension for the
      investigation of pulmonary and multisystem disorders. BAL fluid may be analysed
      for cells and chemical mediators in the diagnosis and also serially for the
      management of several granulomatous disorders including sarcoidosis, extrinsic
      allergic alveolitis, chronic beryllium disease, talc granulomatosis,
      tuberculosis, Langerhans' histiocytosis-x and Crohn's disease. It may also
      provide information in fibrosing alveolitis, collagen vascular disease,
      occupational and drug-induced lung disease, acquired immune deficiency syndrome,
      bronchial asthma, neoplasia, transplantation, pulmonary alveolar proteinosis and
      eosinophilic lung disease. This survey analyses the value of BAL and how it has
      provided a new window for the chest physician.

PMID- 1344041
TI  - Monoclonal antibodies to epithelioid cells in lip biopsy in sarcoidosis.
AB  - The phenotype of infiltrating and residual cells in biopsies of minor salivary
      glands from patients with sarcoidosis and from normal controls, were studied
      using a sensitive two-step indirect immunoperoxidase technique. We found that
      infiltrating lymphocytes were practically absent from salivary gland biopsies in
      the control group, but that in the Sarcoid group the numerous infiltrating
      lymphocytes consisted mainly of T-lymphocytes, mostly T-helper cells (CD4+
      cells). These data correlate positively with other studies on lymphocytic
      infiltration in other organs involved in the immunopathology of sarcoidosis, e.g.
      the lung. In our study the glandular epithelial cells in the salivary gland
      biopsies were HLA-DR positive in the patients with sarcoidosis, especially in
      those specimens from patients with active disease in which 50-80% of the
      epithelial cells expressed an HLA-DR antigen. We observed a positive relationship
      between HLA-DR positive epithelial cells, the expression of interleukin-2
      receptors (IL-2R) and the density of lymphocytic infiltrates. This is in
      accordance with other chronic, lymphocytic infiltratory diseases with HLA-DR
      positive epithelial expression, such as Sjogren's syndrome involving salivary
      glands. This suggests that there might be a common denominator causing disease in
      these cases.

PMID- 1344042
TI  - High frequency of IgM antibodies to coxsackie B virus in sarcoidosis patients and
      patients with asbestos-related lesions.
AB  - By using radioimmunoassay (RIA) for detection of IgM antibodies to Coxsackie B
      viruses (CBV), the occurrence of these antibodies was investigated in patients
      with sarcoidosis and asbestos-related lesions. Sixty-one per cent of the patients
      with sarcoidosis, all patients with benign asbestos pleural effusion, and 67% of
      those with diffuse asbestos-related pleural thickening showed CBV-IgM. Patients
      with healed sarcoidosis or pleural plaques were all negative, and among the
      "healthy" controls seven per cent had CBV-IgM. Thus, there was a high frequency
      of CBV-IgM in patients with sarcoidosis and in those with asbestos-related
      diseases. Since the titres could be the effect of an unspecific polyclonal
      stimulation of the B cells, sera were tested for antibodies to rubella and
      cytomegalovirus, but without any remarkable results.

PMID- 1344043
TI  - Lymphocytic alveolitis and airway responsiveness in recently diagnosed
      sarcoidosis.
AB  - We looked at the relationship between the intensity of the lymphocytic alveolitis
      and airway responsiveness to methacholine, in patients with recently diagnosed
      untreated pulmonary sarcoidosis. We studied 19 subjects, 13 M and 6 F, aged 19-58
      (mean: 36.6) who had a diagnosis of pulmonary sarcoidosis within the last 6
      months (radiologic stages: I, 10 subjects; II, 8; III, 1). One subject had a
      previous history of asthma but was currently asymptomatic. Five were smokers, 5
      ex-smokers and 9 non-smokers. Initial assessment included a flexible bronchoscopy
      with bronchoalveolar lavage (BAL), measurement of expiratory flows, lung volumes,
      CO diffusion and a methacholine inhalation test. Pulmonary function tests were
      repeated six months later, and a second evaluation of airway responsiveness to
      methacholine was obtained in 13 patients. Mean % of lymphocytes, neutrophils and
      macrophages on BAL were respectively: 25.4, 2.3 and 72.4. Mean % of predicted
      values for FVC, FEV1, FEF25-75%, TLC, FRC and DLCO were respectively 91.3, 94.3,
      88.8, 97.6, 102.1 and 91.2. In all subjects FEV1 was > or = 80% and PC20 was in
      the normal range (> 16 mg/ml in all subjects but one who had a PC20 of 12.0).
      There was no correlation between the % of BAL lymphocytes and the initial PC20.
      At 6 months, overall airway responsiveness was unchanged (geometric mean
      initial/6 month PC20 methacholine: 95.9/102.8) whether or not the subjects had a
      high intensity alveolitis (defined as > or = 30% lymphocytes on BAL).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1344044
TI  - B-lymphocyte response in peripheral blood of patients with pulmonary sarcoidosis.
AB  - Sarcoidosis is a granulomatous disorder which can be characterized by various
      immunologic abnormalities including lymphocyte dysfunctions. The purpose of this
      study was to investigate the B-lymphocyte reactivity in the peripheral blood of
      29 various patients with pulmonary sarcoidosis. A significant decrease in the
      production of IgG, IgM and IgA in supernatants of cultivated sarcoidosis B-cells
      both after stimulation with a T-cell dependent polyclonal B-cell activator
      (pokeweed mitogen) and with a T-cell independent polyclonal B-lymphocyte
      activator (Klebsiella pneumoniae) was seen, which suggested a disturbance in the
      B-cell differentiation of sarcoidosis patients. Those patients which were known
      to have a clinically active disease or a high intensity alveolitis in the
      bronchoalveolar lavage fluid showed a greater reduction in the B-cell
      differentiation response. Further evaluation of Ig-G subclasses displayed a
      significant decrease in the secretion of IgG1, IgG3 and IgG4. In contrast to the
      differentiation, the proliferation response of sarcoidotic peripheral blood
      lymphocytes to different mitogens did not differ from healthy controls.

PMID- 1344045
TI  - Angiotensin-converting enzyme in bronchoalveolar lavage fluid in sarcoidosis.
AB  - This is the first Australian study of angiotensin converting enzyme (ACE) in
      bronchoalveolar lavage fluid in 51 patients with sarcoidosis. The aim was: 1) to
      establish the range of lavage ACE in healthy smokers and non-smoking patients
      with sarcoidosis. 2) to evaluate the clinical usefulness of lavage ACE. Seventeen
      control subjects and 51 sarcoid patients all underwent bronchoalveolar lavage,
      the latter also having 67Gallium scan, spirometry and carbon monoxide uptake.
      Eighteen patients had all tests repeated six months later. Lavage ACE was
      significantly higher in sarcoid non-smokers than control non-smokers (p < 0.05).
      In the 51 sarcoid patients, lavage ACE/albumin ratios were 10-fold higher than
      serum ACE/albumin ratios (p < 0.0001). In sarcoid patients with raised
      intrathoracic 67Gallium uptake, lavage ACE was significantly higher than those
      patients with normal uptake (p < 0.05). Expressing lavage ACE as ACE/albumin
      ratios reduced the statistical significance of correlations with other
      parameters, eg, lavage % lymphocytes, and lavage IgG. Lavage ACE levels changed
      concordantly with lung function 67Gallium scan and lavage lymphocytes, albumin
      and IgG. However, the wide distribution of lavage ACE in control and sarcoid
      subjects and the influence of smoking history severely limits its clinical
      application.

PMID- 1344046
TI  - Idiopathic granulomatous bronchitis. An unusual form of known granulomatous lung
      diseases or an unknown disease?
AB  - We describe two patients demonstrating a granulomatous inflammation of bronchial
      mucosa characterized clinically by a persistent dry cough, lack of manifestations
      of bronchial asthma, normal level of serum IgE and serum ACE, inflamed bronchial
      mucosal appearance consisting of edema, erythema, bleeding and narrowing and
      recovering without specific treatment. Histopathological findings of the
      bronchial inflammation of our patients were characterized by noncaseating
      granuloma formation consisting of epithelioid cells and multinucleated giant
      cells with infiltration of lymphocytes, plasma cells and eosinophils. The
      bronchial granulomatous inflammation of our patients was thought to differ from
      that of diseases which have been known, to our knowledge, as diseases
      demonstrating a granulomatous inflammation of bronchial mucosa. Although the
      pathogenesis of the disease could not be clarified by a careful search of special
      staining and culturing for the infective agent, it was most suggestive of non
      specific inflammation with a granulomatous response to some sort of inhaled
      agents.

PMID- 1344047
TI  - Diffuse panbronchiolitis observed in an Italian male.
AB  - We describe a case of a 43 year old man who presented with productive cough,
      dyspnea, severe obstructive ventilatory failure and diffuse micronodular shadows
      on chest roentgenogram. Bronchoalveolar lavage fluid analysis showed an increased
      total cellularity sustained by a huge neutrophilia. Sweat test was negative.
      Transbronchial lung biopsy and autopsy showed unit lesion of diffuse
      panbronchiolitis. This report represents, to the best of our knowledge, the first
      case of diffuse panbronchiolitis observed in Europe.

PMID- 1344048
TI  - Monoclonal gammopathy of undetermined significance in sarcoidosis. Two case
      reports.
AB  - We report the first two cases of monoclonal gammopathy of undetermined
      significance associated with sarcoidosis. Both of our patients had biopsy proven
      sarcoidosis with elevated proteins. Further workup of sarcoidosis patients with
      elevated proteins is recommended to diagnosis monoclonal gammopathy.

PMID- 1344049
TI  - Sarcoidosis and malaria. Possible interactions.

PMID- 1344050
TI  - Is sarcoidosis related to exposure to pets or the housing conditions? A case
      referent study.
AB  - On the assumption that sarcoidosis could be caused by inhalation of antigens
      stemming from pets a case-referent study was set up to examine this idea. Thirty
      nine patients with biopsy-proven sarcoidosis were compared with 106 sex- and age
      matched control persons on the exposure to pets, present and previous, in the
      households. In addition data on basic housing conditions and smoking habits were
      collected. No statistical difference in the absolute frequency of dogs, dogs
      and/or cats or any pet in the two groups was observed counting only pets kept for
      more than 2 years prior to the year of diagnosis. Equally the basic housing
      conditions (size, type of and age of dwelling, family size) were identical. There
      was a tendency of more non-smokers in the sarcoidosis group (46% vs 33%) but the
      difference did not reach statistical significance. However it cannot be excluded
      that inhalable antigens stemming from pets initiate sarcoidosis among susceptible
      individuals.

PMID- 1344051
TI  - Multi-element follow up in biological specimens of hard metal pneumoconiosis.
AB  - The movement of Co and the other components of the hard metal in the body fluids,
      their solubility, their links to the cells and proteins of the body, and their
      clearance are largely unknown. The first aim of this work is to evaluate whether
      Neutron Activation Analysis (NAA), a new analytical technique based on the
      radiochemical separation of samples irradiated in a Nuclear Reactor, may be
      suitable for studying the movement of elements in tissues or body fluids of
      workers over time. We have investigated seven hard metal workers, all employed in
      the grinding process, with NAA studies (single study in two, follow-up in five)
      of 29 elements on lung tissue, BAL fluid, blood, urine, pubic hair, toenails and
      sperm. In three, the diagnosis of hard metal pneumoconiosis was easy; in the
      other four, due to evident bilateral hilar lymphadenopathy, it was difficult to
      distinguish between pneumoconiosis and sarcoidosis stage II, and the final
      diagnosis, after pulmonary biopsy, was hard metal pneumoconiosis in three, and
      sarcoidosis in one. In spite of high potential, NAA gives a number of unexpected
      results, with apparent controversies and no clear relationship in the evolution
      of levels of Co, W and Ta: there is no simple explanation for such apparent
      inconsistencies at present, so that the study of the movement of elements in body
      fluid sometimes appears disappointing with this technique. Other observations
      were noted from the data available: 1) the concentration of elements (Co, Ta, W)
      in lung tissue is far higher than in BAL fluid, but the factor is so variable
      that BAL fluid cannot be taken as representative of the concentration of elements
      in lung tissue. 2) High concentrations in tissues or body fluids are indicative
      for exposure, but not for disease. In the light of available data, there are no
      levels above which development of disease is inevitable. 3) When the problem is
      to distinguish between sarcoidosis and pneumoconiosis in exposed subjects, the
      concentration of elements is of no value, and the pulmonary biopsy is still
      necessary. However a NAA study may be helpful to confirm the presence of the
      offending agent, and to avoid pulmonary biopsy in cases where the occupational
      history is unclear.

PMID- 1344052
TI  - Sarcoidosis in Spain.
AB  - We review the Spanish literature on sarcoidosis, and describe the most important
      epidemiological and clinical findings. Recent epidemiological data show a
      cumulative annual incidence rate of 1.36 per 100,000 inhabitants. The most
      relevant clinical aspects are the high incidence of Lofgren syndrome (48% of the
      cases), and the low percentage of cases diagnosed by routine chest X-ray (9%).
      Findings of intrathoracic and extrathoracic sarcoidosis, biopsy procedures, Kveim
      test, lung function tests, as well as the activity markers are, in general,
      similar to those previously described in the literature. The overall prognosis of
      sarcoidosis in Spain is good.

PMID- 1344053
TI  - Sarcoidosis in Tuscany. A preliminary report.
AB  - A retrospective study was carried out by a computerized questionnaire in a sample
      of 109 sarcoidosis patients (43 men, 66 women) diagnosed between 1977 and 1990 in
      Pisa. 94% of the patients were resident in Tuscany. The onset of disease was
      earlier in the men than in the women; in 73% of the patients the symptoms were
      first noticed between February and July with two incidence peaks; 71% of them had
      never smoked; 10% of patients were symptom-free and the disease was discovered by
      chance; the other patients (90%) underwent chest X-ray because of joint symptoms
      (35%), erythema nodosum (34%), cough (28%), dyspnoea (27%), and fever (24%) which
      was often associated with other symptoms. Symptoms from the respiratory tract was
      present in 66 patients (61%); 58% of patients were resident in rural areas; the
      level of education was limited to primary school in 50% of the patients; as to
      the prevailing working positions, 27% were clerical workers, 24% manual workers,
      and 26% housewives.

PMID- 1344054
TI  - Isolated portal hypertension in sarcoidosis. A report of two Indian patients.
AB  - Two patients with portal hypertension due to sarcoidosis are described. While one
      of them had severe bleeding from varices the other was asymptomatic. Endoscopic
      sclerotherapy obliterated the bleeding varices and is planned for the other
      patient if he bleeds.

PMID- 1344055
TI  - Symptomatic rib lesions as the primary presentation of sarcoidosis. Report of two
      cases and review of literature.
AB  - Skeletal involvement in sarcoidosis is considered a manifestation of chronic
      disease. Rib lesions, while rarely reported, have been usually asymptomatic and
      often associated with vertebral sarcoidosis. Here, we report two patients with
      symptomatic rib lesions in sarcoidosis. Both patients were black males. In both
      cases, chest X-rays lacked characteristics of pulmonary sarcoidosis. A definite
      diagnosis was made on rib biopsies and confirmed by the positive Kveim test. One
      case was particularly interesting in that low back pain preceded the right hilar
      adenopathy for many years. This suggests that sarcoidosis involving the bone may
      occur at early stage of disease, and that low back pain in young male may be the
      first presentation of sarcoidosis. A literature review of osseous involvement in
      sarcoidosis reveals that skeletal lesions in sarcoidosis may preferentially
      manifest in the axial skeleton in some individuals.

PMID- 1344056
TI  - Sarcoidosis in Poland.

PMID- 1344057
TI  - Sarcoidosis in the Nordic countries 1950-1987.

PMID- 1344058
TI  - Aspects on the alveolar accumulation of T cells in sarcoidosis.

PMID- 1344059
TI  - Bronchoalveolar lavage and biochemical markers in serum for monitoring disease
      activity and prognosis of sarcoidosis.

PMID- 1344061
TI  - A call for epidemiological research in sarcoidosis.

PMID- 1344060
TI  - Sarcoid heart disease.

PMID- 1344062
TI  - Epidemiology of sarcoidosis.

PMID- 1344063
TI  - The role of integrins in the immune response.
AB  - The integrin is one of at least three different families of adhesion molecules.
      Integrins are heterodimeric cell surface receptors, important for adhesion,
      migration and cellular interactions of immune cells. There are at least 6
      subgroups of integrins, each defined by a common beta submit (beta 1-beta 6)
      which shares multiple alpha subunits. Among them are the receptors for
      fibronectin, laminin, vitronectin, as well as the very late activation antigens
      (VLA 1-6) and the C11/CD18 complex. The role of these molecules in the immune
      response is discussed with special focus on the beta 2 integrins (CD11/CD8) and
      their ligand ICAM-1 (CD549).

PMID- 1344064
TI  - Effect of cigarette smoking on prevalence of summer-type hypersensitivity
      pneumonitis caused by Trichosporon cutaneum.
AB  - We investigated the effect of cigarette smoking on the prevalence of summer-type
      hypersensitivity pneumonitis (SHP) caused by Trichosporon cutaneum. In the adult
      family members of SHP patients, we found that 27 of 41 (65.9%) nonsmokers were
      SHP patients, compared with 3 of 11 (27.3%) smokers (p less than .05). Also, the
      prevalence of anti-T. cutaneum antibody was significantly lower in the smokers (p
      less than .05). A questionnaire provided to 209 SHP patients revealed that the
      smoking rates of male and female SHP patients were significantly lower (p less
      than .01) than rates in the normal Japanese population. However, no difference
      was found in serum anti-T. cutaneum antibody activities or the bronchoalveolar
      lavage lymphocyte phenotypes for smoking and nonsmoking SHP patients. It was
      concluded that cigarette smoking had a suppressive effect on the outbreak of SHP,
      but smoking caused no further suppression after the disease was established.

PMID- 1344065
TI  - Issues in state newborn screening programs.

PMID- 1344066
TI  - Nonculture tests for genital tract chlamydial infection. What does the package
      insert mean, and will it mean the same thing tomorrow?

PMID- 1344067
TI  - Robin sequence and a deficiency of the left forearm in a girl with a deletion of
      chromosome 4q33-qter.
AB  - We have investigated a patient with the Robin sequence and a unilateral
      deficiency of the left forearm. She was found to have a terminal deletion of the
      long arm of chromosome 4, del(4)(q33). The clinical manifestations of this
      patient differ from those of 7 previously described patients with a deletion of
      the same segment.

PMID- 1344069
TI  - Medicolegal and nursing practice in the private sector.

PMID- 1344068
TI  - Brain-oriented intensive care after resuscitation from cardiac arrest.
AB  - The 'chain-of-survival' concept has gained general acceptance in the care of
      cardiac arrest victims. Most standards and guidelines for cardiopulmonary
      resuscitation, however, focus on the initial links in the chain. We consider
      appropriate in-hospital care for the survivors a logical extension of the chain
      of survival. In recent years extensive research activity has probed the
      pathophysiology and pharmacology of postischemic reperfusion. The present review
      discusses the current understanding of mechanisms for cerebral damage following
      global ischemia. Promising pharmacological principles for protection or
      resuscitation from cerebral ischemia are reviewed. None of them are considered
      ready for clinical application. Clinical guidelines are proposed, based on the
      reviewed data and previously published clinical observations. Cornerstones of the
      proposed brain-oriented intensive care protocol are: (1) hemodynamic monitoring
      and meticulous treatment of circulatory disturbances, (2) controlled ventilation
      providing normoventilation and normoxia to all comatose patients, (3) avoiding
      hyperglycemia and hyperthermia in comatose patients, (4) adequate analgesia and
      sedation, tempered by the understanding that oversedation impedes neurological
      evaluation without promoting recovery. An accurate prognosis can usually be made
      48-72 h after resuscitation. This permits reevaluation and assignment to an
      appropriate level of continued hospital care.

PMID- 1344070
TI  - Neuroanatomy of the ocular motor pathways.
AB  - Oculomotor-related structures in the brain stem extend from the rostral
      mesencephalon to the hypoglossal nucleus in the caudal medulla. This chapter
      reviews their location in man, their connections and some basic features of their
      function; these are summarized in Table 1. In addition to the extraocular motor
      nuclei (the oculomotor, trochlear and abducens nuclei) the brain stem contains
      premotor areas responsible for all five different types of eye movements and for
      gaze-holding. These premotor structures include the riMLF and PPRF for the
      generation of vertical/torsional and horizontal saccades, respectively. The role
      of the vestibular nuclei in the VOR and optokinetic responses is well
      established, and they probably also mediate smooth pursuit eye movements along
      with the dorsolateral pontine nuclei and the floccular region. In contrast, there
      is only scanty evidence for the function of the accessory optic nuclei relaying
      optokinetic information in man. Little is known about the neuroanatomy of the
      premotor areas for convergence. There is accumulating evidence that the INC and
      the vestibular and perihypoglossal nuclei are essential for the maintenance of
      gaze.

PMID- 1344071
TI  - Ocular motor dysfunction in stupor and coma.
AB  - Ocular motor disorders in stupor and coma are important clinical signs which are
      easily accessible with observation and a few bedside manoeuvres. Although the
      manifold signs of ocular motor dysfunction may be confusing to most clinicians,
      many of the signs can be attributed to clear pathophysiological mechanisms. This
      holds for conjugate eye deviations as well as for most spontaneous eye movements
      in coma. Using simple methods to elicit reflex eye movements, in most cases a
      lesion site within or outside the brain stem can be determined. It is stressed
      that an exact description and documentation of the ocular motor deficit is
      necessary. The following key aspects should be included in such a documentation:
      pupil size and reaction, conjugate or disconjugate eye position, spontaneous eye
      movements and VOR elicited either by head rotation or caloric irrigation. The
      latter allows assessment of the ocular motor integrator. The VOR may be intact,
      indicated by full compensatory eye movements, but the gaze-holding mechanism
      (integrator) can be defective, thus permitting the eyes to drift back to the
      primary position.

PMID- 1344072
TI  - Cyclorotation of the eyes and the subjective visual vertical.
AB  - Pathological CR of the eyes and deviations of the SVV are among the most
      sensitive clinical brain stem signs. In acute unilateral brain stem infarctions,
      deviations of the SVV occur in 94% of cases and CR of one or both eyes is found
      in 88%. Deviations of CR and the SVV are typically ipsiversive with
      pontomedullary lesions and contraversive with pontomesencephalic lesions. They
      may involve a complete OTR, the triad of lateral head tilt, skew deviation and
      CR. There is a directional linkage between CR and the SVV (i.e. either right or
      left tilt), but the net tilt angles do not always match quantitatively.
      Pathological CR and deviations of the SVV obviously represent dysfunction of the
      VOR in the roll plane, which is subserved by both otolith and vertical canal
      inputs.

PMID- 1344073
TI  - Disorders of head-eye coordination.
AB  - Head-eye coordination subserves the rapid transference of gaze and between gaze
      shifts stabilizes fixation on stationary or smoothly moving targets. The
      coordination involves various combinations of the components of head movement,
      saccadic eye movements and visual and vestibular slow phase eye movement whose
      fine tuning may be adjusted, to an extent currently debated, by higher order
      mechanisms. Disorders of head-eye coordination may result in loss of acuity when
      slow phases are impaired or difficulty with reorientation if there is difficulty
      with saccades or head movement. Pathophysiology in the brain stem affecting
      individual components of eye movement may often be identified with success,
      particularly for the horizontal system, but the organization of other functions,
      notably pursuit suppression and vertical movements, are little understood.
      Similarly little is known about the disorders of the overall pattern of
      coordination--'gaze types'--including the apraxias, which have been attributed to
      cortical, basal ganglia or even cerebellar dysfunction and are reported in an
      almost bewildering variety of diseases. The development of coordination in
      infancy is a rich field in which there have been few studies with adequate
      observational techniques. The differentiation between congenital disorders whose
      severity may subsequently wax or wane, variants on normal development and
      acquired disorders poses a clinical problem which could largely be resolved with
      adequate recording techniques. For the future there is the tantalizing promise
      that once the principles of coordination are understood, we can move on to the
      more intriguing questions of how a certain 'toss of the head' and 'look in the
      eye' not only transfer gaze but can also be so meaningful.

PMID- 1344074
TI  - Behavioural and neural correlates of vestibular compensation.
AB  - Sudden complete loss of input from one labyrinth results in a massive change in
      behaviour. A vigorous horizontal ocular nystagmus occurs together with postural
      changes. These dramatic changes are short-lived and within about a week they have
      almost disappeared. This very rapid recovery has been the basis for the
      postulation that vestibular compensation is a textbook model for the study of
      neural plasticity in the central nervous system. Whilst the behavioural recovery
      is dramatic, quantitative testing reveals the loss and the permanent asymmetry of
      the system (Table 1). Recordings from single neurones show that many neurones in
      the ipsilesional VN are silenced by the unilateral loss, but as they start to
      fire again, so the spontaneous nystagmus declines. The major question which is
      still unanswered is the cause of the return of the firing of neurones in the
      ipsilesional VN. The answer may be found by studies of the neurochemistry of the
      VN using brain slice preparations. This review shows some of the errors which
      have been made by attempting to infer purely vestibular function from
      measurements of eye movements when other sources of ocular motor control may
      operate.

PMID- 1344075
TI  - Pathophysiology of rapid eye movements in the horizontal, vertical and torsional
      directions.
AB  - Saccades and fast phases of optokinetic or vestibular nystagmus are rapid eye
      movements which are generated in the reticular formation of the brain stem.
      Palsies of rapid eye movement generation therefore always point towards an
      infratentorial lesion. Two cell assemblies are responsible for the generation of
      rapid eye movements: the PPRF, which triggers all rapid eye movements and in this
      sense plays an important coordinating role in addition to generating movements
      with a horizontal movement component, and the riMLF in the mesencephalon for
      movements which have a vertical or torsional direction component. As neurone
      populations are anatomically segregated according to their respective on
      directions, focal lesions lead to the loss of rapid eye movements in particular
      directions (Table 2). Such palsies of rapid eye movement generation which are
      direction specific can be distinguished from dysmetria, which points towards a
      cerebellar lesion, or the difficulty to trigger a saccade to a particular target,
      which can involve cortical systems.

PMID- 1344076
TI  - Clinical features and pathogenesis of acquired forms of nystagmus.
AB  - Nystagmus is a common finding in patients with disease affecting the brain stem
      and cerebellum. Basic research into mechanisms that normally control eye
      movements has led to a better understanding of the pathogenesis of different
      types of acquired nystagmus. Nystagmus is caused by disorders of the mechanisms
      that normally function to hold gaze steady: the vestibular system, the gaze
      holding mechanism, the visual stabilization system and the smooth pursuit system.
      Thus, evaluation of a patient's nystagmus requires a systematic examination of
      each functional class of eye movements. In addition, it is important to determine
      the direction of the nystagmus for different angles of gaze and head positions,
      and the effects of monocular and binocular visual fixation upon the nystagmus.
      Measurement of the nystagmus waveform, using reliable methodology, is often
      helpful in securing a diagnosis. Such measurements help differentiate acquired
      nystagmus from congenital forms of nystagmus and from saccadic disorders that
      lead to instability of gaze.

PMID- 1344077
TI  - Nuclear and infranuclear disorders.
AB  - Lesions of the brain stem can either affect the nuclei or the fascicles of the
      third, fourth or sixth cranial nerves and thus produce ocular motor disorders.
      Lesions of the oculomotor nuclear complex differ from lesions of the third nerve,
      since the motoneurones in the nucleus are specifically grouped. Similarly, a
      lesion of the sixth nerve nucleus results in a conjugate gaze palsy and not in an
      abducens palsy, because of 'interneurones' being intermingled with the abducens
      motoneurons. Isolated lesions of a nerve fascicle, which is the part of the
      cranial nerve running through the brain stem, usually cannot be distinguished
      clinically from lesions of the nerve outside the brain stem unless other brain
      stem signs are present. In the case of an isolated ocular motor nerve palsy,
      modern imaging techniques, particularly magnetic resonance imaging, may help to
      localize the lesion to the brain stem. Most often, however, brain stem lesions
      also involve structures surrounding the ocular motor nuclei or fascicles,
      sometimes leading to characteristic eponymic syndromes. In congenital eye
      movement disorders the pathoanatomical situation is more complex. Since the
      lesion takes place during intrauterine or early postnatal development, corrective
      misdirection of neurones occurs in addition to aplasia or hypoplasia of parts of
      the cranial nerves. Correspondingly, abnormal movements accompanying an attempted
      eye movement can be observed in some characteristic syndromes.

PMID- 1344078
TI  - Smooth pursuit disorders.
AB  - Smooth pursuit is a relatively recent eye movement which has developed in frontal
      eyed species. The smooth pursuit system is involved during foveal smooth pursuit,
      the 'rapid' component of OKN slow phase and VOR suppression. The cortical areas
      controlling smooth pursuit (at the temporo-parieto-occipital junction and in the
      FEF) send ipsilateral projections onto the pontine nuclei, mainly the DLPN,
      passing through the anterior part of the midbrain. A midbrain or DLPN lesion
      results in ipsilateral smooth pursuit impairment (i.e. decreased gain) (Table 1).
      After the pontine nuclei, all smooth pursuit pathways pass through the
      cerebellum. They project onto the flocculus, mainly contralaterally (first
      decussation of the lateral smooth pursuit circuitry), and bilaterally onto the
      posterior vermis. Eye velocity is encoded in the activity of the floccular
      Purkinje cells, whereas target velocity is encoded in that of the vermal Purkinje
      cells. Unilateral floccular lesions and posterior vermal lesions (involving both
      sides of this structure) result in ipsilateral and bilateral smooth pursuit
      impairment, respectively. The flocculus sends an ipsilateral inhibitory
      projection onto the MVN, the y-group nucleus and the SVN, controlling
      contralateral, upward and perhaps downward smooth pursuit, respectively.
      Alternatively, the downward smooth pursuit pathway could pass through the dentate
      nuclei. The MVN sends a contralateral excitatory projection onto the abducens
      nucleus (second decussation of the lateral smooth pursuit circuitry). These
      anatomical and physiological characteristics of lateral smooth pursuit pathways,
      in addition to the results of lesion studies, suggest that, besides the floccular
      inhibitory Purkinje cell, there is another inhibitory neurone in the circuitry
      preceding this cell, perhaps within the flocculus itself. The posterior vermis
      projects onto the fastigial nuclei, which also control smooth pursuit. These
      nuclei could send efferents to those periabducens cells involved in ipsilateral
      smooth pursuit. The final part of the pathways involved in vertical smooth
      pursuit could pass mainly through the BC, originating in the y-group nucleus for
      upward movement and in the SVN or the dentate nuclei for downward movement.
      Alternatively, a ventral tegmental tract could transmit upward smooth pursuit
      signals between the y-group nucleus and the oculomotor nucleus. The MLF also
      belongs to this vestibulo-oculomotor circuitry, but does not appear to be crucial
      for vertical smooth pursuit since this eye movement is only partially impaired
      after MLF lesions. Lastly, parallel to the direct vestibulo-ocular motor nuclei
      pathways, there are other pathways passing through the brain stem integrators,
      converting eye velocity signals to eye position signals during all eye movements,
      including smooth pursuit.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1344079
TI  - Internuclear ophthalmoplegia: pathophysiology and diagnosis.
AB  - The main findings in unilateral INO are paresis of adduction in the eye on the
      side of the lesion (for conjugate but not vergence eye movements) and abduction
      nystagmus in the eye on the side opposite to the lesion. A skew deviation (eye
      usually higher on the side of the lesion) or a dissociated, mixed vertical
      torsional nystagmus, with the eye beating down on the side of the lesion, may
      also occur. The main findings in bilateral INO are paresis of adduction in both
      eyes, bilateral abduction nystagmus and, in the vertical plane, impaired gaze
      holding, vestibular responses and smooth tracking. Abduction nystagmus in INO may
      have a number of causes; probably most common are a gaze-evoked nystagmus
      superimposed on adduction weakness and adaptation to adduction weakness. Most of
      the findings in INO can be explained by interruption of projections from abducens
      internuclear neurones, mediating adduction, and from the vestibular nuclei,
      mediating both canal- and otolith-induced reflexes as well as vertical gaze
      holding and pursuit. Extension of the lesion to structures near but outside the
      MLF, or involvement of cell bodies intermixed with MLF fibres, may also be
      important in the pathogenesis of the abduction nystagmus and the occasional
      slowing of abducting saccades.

PMID- 1344080
TI  - Use of stress electrocardiography in practice.

PMID- 1344081
TI  - Use of antiplatelet medication for prevention of myocardial infarction and
      stroke.
AB  - Patients who suffer a heart attack can reduce the risk of another attack by 20%
      by taking 325 mg aspirin daily or every other day. The risk of stroke can be
      reduced by 50% in patients who experience atrial fibrillation or transient
      ischemic attacks. Although the benefit of aspirin use in women is controversial,
      data that suggest that women benefit as well as men are emerging. Antiplatelet
      drugs should be used only as adjunctive therapy and should not divert one's
      attention from the more important task of reducing major risk factors, such as
      smoking, hypertension.

PMID- 1344082
TI  - Use and toxicity of digitalis.

PMID- 1344083
TI  - Transient ischemic attacks: recognition and management.

PMID- 1344084
TI  - The future of thrombolytic therapy.

PMID- 1344085
TI  - The "chain of survival" concept: how it can save lives.
AB  - The AHA Committee on Emergency Cardiac Care recommends that all communities
      strengthen the four links in the chain of survival: Early Access: Install an
      enhanced 911 emergency dispatch system. Provide certification training to all
      emergency medical dispatchers. Develop community-wide education and publicity
      programs that focus on cardiac emergencies and a proper response by citizens.
      Early CPR: Implement and support community CPR training programs. In these
      programs emphasize early recognition, early telephone contact with the EMS
      system, and early defibrillation. Use training methods that will increase the
      likelihood that citizens will start CPR. Adopt targeted CPR programs. Implement
      programs for dispatcher-assisted CPR. Early Defibrillation: Adopt the principle
      of early defibrillation. Train all emergency personnel who perform basic CPR to
      operate an automated external defibrillator. Implement more widespread use of
      automated external defibrillators by community responders and allied health
      responders. Early Advanced Life Support: Coordinate advanced life support units
      with first-response units that provide early defibrillation. Develop procedures
      that combine rapid defibrillation by first-response units with rapid intubation
      and intravenous medications by the advanced life support units.

PMID- 1344086
TI  - Chest pain: angina pectoris and related states.

PMID- 1344087
TI  - Prevention and treatment of stroke.

PMID- 1344088
TI  - Radiographic diagnosis of heart failure.
AB  - In the initial evaluation of cardiac patients, valuable information can be
      derived from the chest radiograph. In general, acute left-sided heart failure is
      shown by an erate cardiomegaly, cephalization of the pulmonary vascularity, and a
      mixed type of pulmonary edema. Gross alveolar pulmonary edema with a normal or
      minimally enlarged heart. Subacute failure is associated with modcardiomegaly,
      striking cephalization, and interstitial pulmonary edema are hallmarks of chronic
      left-sided heart failure. Right-sided heart failure is shown by enlarged systemic
      veins and right-sided chambers as well as pulmonary oligemia. Pleural effusions
      in heart failure tend to be bilateral or unilateral on the right side.

PMID- 1344089
TI  - Recognition and treatment of infective endocarditis.

PMID- 1344090
TI  - Atrial fibrillation: conventional wisdom reappraised.
AB  - For years the conventional approach to treatment of atrial fibrillation has
      centered around use of digoxin for rate control and type IA agents for conversion
      to normal sinus rhythm and has avoided use of anticoagulation therapy for most
      patients. Current data suggest that new conventions are needed. beta-Blockers or
      calcium channel blockers should be considered equal to, if not better than,
      digoxin for rate control. Type IA agents are still the drugs of choice for
      conversion to and maintenance of normal sinus rhythm, but the newer agents
      propafenone and flecainide, and perhaps even amiodarone, may be more efficacious
      if preliminary data are truly indicative of their effect. The use of
      antiarrhythmic agents requires caution and careful attention to factors that may
      predispose patients to their inherent proarrhythmic effects. Finally,
      anticoagulation therapy is no longer reserved for a few patients but should be
      used in low doses in most patients (when not contraindicated) to lower risk of
      stroke. This new approach must be challenged as well to minimize the morbidity
      and mortality of this common clinical problem.

PMID- 1344091
TI  - Pericardial disease.

PMID- 1344092
TI  - The endothelial cell.
AB  - This article reviewed several important functions of the endothelium as they
      pertain to both normal vascular function and pathology. The endothelium has other
      functions that were not discussed, including regulation of vascular permeability
      and elaboration of several growth-promoting and growth-inhibiting factors. It is
      almost certain that as our knowledge of endothelial cell function increases,
      other roles of this important cell will be discovered. Many scientists are
      investigating how endothelial interaction with the remainder of the vessel and
      blood elements is altered by various vascular diseases. Efforts directed toward
      correcting or modifying endothelial cell function in these diseases will lead to
      new and innovative therapeutic approaches.

PMID- 1344093
TI  - The importance of the initial cardiovascular examination.

PMID- 1344094
TI  - Cardiac auscultation: the first and second heart sounds.

PMID- 1344095
TI  - Use and misuse of digitalis blood levels.

PMID- 1344096
TI  - Syncope: pursuing the common and prognostically important causes.

PMID- 1344097
TI  - Use of angiotensin converting enzyme inhibitors.

PMID- 1344098
TI  - Active viral myocarditis: application of current knowledge to clinical practice.

PMID- 1344099
TI  - Diagnosis and treatment of ventricular tachycardia.

PMID- 1344100
TI  - Obesity: location matters.

PMID- 1344101
TI  - Is angiotensin II a growth factor masquerading as a vasopressor?
AB  - The actions of angiotensin II can be described in terms of the three paradigms
      listed in Table 1. According to the first paradigm (organ physiology),
      angiotensin II is a pressor, while the second (cell biochemistry) views it as an
      extracellular messenger that, by promoting Ca2+ release within cells, causes
      vasoconstriction and a weak positive inotropic response by the heart. However,
      neither of these paradigms fully explains the remarkable ability of angiotensin
      converting enzyme inhibitors to improve the prognosis for patients with heart
      failure. To account for these clinical effects of angiotensin converting enzyme
      inhibitors, we will probably need to invoke the third paradigm (gene expression),
      which views angiotensin II as a growth factor that promotes and modifies protein
      synthesis. Angiotensin II, therefore, should probably not be viewed simply as a
      vasoconstrictor with a side effect to promote hypertrophy, but instead as a
      growth factor that, because it utilizes Ca2+ to mediate its effects on gene
      expression, also increases smooth muscle tone and myocardial contractility. This
      view of angiotensin II as a growth factor helps us to understand the clinical
      benefit of angiotensin converting enzyme inhibitors as arising from inhibition of
      maladaptive changes in the failing heart (gene expression) as well as from the
      reduced afterload (organ physiology) that results from decreased smooth muscle
      tone (cell biochemistry).

PMID- 1344103
TI  - The value of examining the patient in the upright position.

PMID- 1344102
TI  - Cholesterol management strategies for patients with heart disease.

PMID- 1344104
TI  - Cardiovascular benefits of smoking cessation.
AB  - Cigarette smoking causes significant exposure to nicotine, which increases heart
      rate, blood pressure, and thus myocardial oxygen demand, and to carbon monoxide,
      which decreases the oxygen-carrying capacity of the blood because of
      carboxyhemoglobin formation. Cigarette smoking also predisposes the patient to
      coronary vasoconstriction. Smoking cessation results in the early elimination of
      nicotine and carbon monoxide from the system and decreases the risks of ischemia
      based on these mechanisms. Over the long term, smoking cessation results in
      elimination of the increased risk of myocardial infarction in patients without
      previous heart disease as early as 2 years after smoking stops. In addition, for
      patients with known coronary artery disease, smoking cessation results in an
      increase in HDL level, which may result in a retardation of atherogenesis and
      reduced cardiovascular morbidity and mortality. It is important for all
      physicians to reiterate both the short- and long-term risks of cigarette smoking
      as well as the good news-that smoking cessation results in a substantial, if not
      complete, reversal of the risk of myocardial infarction and death, particularly
      for patients with established coronary artery disease. In light of those
      established facts, efforts to develop more effective methods to help patients
      quit smoking must be increased so patients can realize these important health
      benefits.

PMID- 1344105
TI  - Is prevention of all cardiovascular birth defects a feasible goal?

PMID- 1344106
TI  - Prophylactic lidocaine for suspected acute myocardial infarction?

PMID- 1344107
TI  - Auscultatory findings in mitral valve prolapse.

PMID- 1344108
TI  - Electrophysiological studies: who to refer.

PMID- 1344109
TI  - Diagnosis of pulmonary artery hypertension.
AB  - The challenge for the clinician is to detect and diagnose pulmonary artery
      hypertension early, when treatment can be most beneficial. This can be done only
      if the clinician looks for pulmonary hypertension and confirms the diagnosis
      through history taking, physical examination, and electrocardiographic and chest
      roentgenographic evaluation.

PMID- 1344110
TI  - Coarctation of the aorta: difficulties in clinical recognition.
AB  - Coarctation can be recognized by physical examination alone early in a person's
      life, except in instances in which the obstruction is very mild. While some cases
      remain mild for a lifetime, others become progressively worse during adolescence
      or adulthood with typical manifestations of upper-extremity hypertension and
      imperceptible pulses in the lower extremities. It is especially urgent and
      sometimes difficult to recognize coarctation in infants with congestive cardiac
      failure just as it is to identify older children and adolescents with
      asymptomatic but severe systemic hypertension. There may be medical or legal
      implications in failing to do so.

PMID- 1344111
TI  - Neurological and psychosocial disorders in adults with congenital heart disease.

PMID- 1344112
TI  - Hypertension due to renal arterial disease.
AB  - Renal arterial disease occurs in 3-5% of patients with systemic hypertension. It
      is important to determine the type of lesion by arteriography to understand the
      natural history of the specific disease and to choose appropriate therapy. Some
      have questioned why arteriography should be performed if an operation or
      percutaneous transluminal renal angioplasty is not considered. One must keep in
      mind that if the arteriographic characteristics are known, the specific lesion
      and its course may be predicted, resulting in better management of the disease.
      In patients with a unilateral lesion angiotensin converting enzyme inhibitors are
      efficacious, but calcium antagonists may also be used. However, if therapy does
      not provide optimum control of blood pressure or the impairment of renal function
      progresses, then percutaneous transluminal renal angioplasty or surgery should be
      reconsidered.

PMID- 1344113
TI  - Heart disease and mitochondrial DNA mutations.

PMID- 1344114
TI  - What's wrong with Mr. Jones, a 58-year-old man with cerebrovascular disease?

PMID- 1344115
TI  - Alcohol as a risk factor for stroke.

PMID- 1344116
TI  - Cardiac auscultation: the third and fourth heart sounds.

PMID- 1344117
TI  - Treatment of systolic hypertension.

PMID- 1344118
TI  - Prinzmetal's angina (variant angina).

PMID- 1344119
TI  - Stroke associated with thrombolytic therapy for acute myocardial infarction.

PMID- 1344120
TI  - Silent ischemia.

PMID- 1344122
TI  - Abdominal aortic aneurysm: natural history and treatment.

PMID- 1344121
TI  - Syndrome X: understanding and evaluating the patient with chest pain and normal
      coronary arteriograms.

PMID- 1344123
TI  - Long QT syndrome.

PMID- 1344124
TI  - Coronary artery disease in women.

PMID- 1344125
TI  - Angioscopic examination of the coronary arteries: what have we learned?

PMID- 1344126
TI  - On recognizing ventricular tachycardia.

PMID- 1344127
TI  - Etiology: unknown or ignored?
AB  - It is important to determine whether a patient's medical problem is a
      physiological complication that has resulted from a disease process (such as
      heart failure that is a complication of calcific aortic valve stenosis) or a
      structural complication that has resulted from a disease process (such as a
      stroke due to an embolus from a left atrial thrombus caused by atrial
      fibrillation in a patient with mitral stenosis). Whereas treatment is available
      for heart failure and stroke regardless of the cause, the progress of medicine is
      nullified when treatment is not directed at the etiology of heart failure and
      stroke. Finally, and most importantly, the identification and treatment of
      cardiovascular diseases that may cause heart failure and stroke may provide the
      physician with an opportunity to prevent these serious complications. The New
      York Heart Association four-part diagnosis (a complete diagnosis) requires the
      physician to consider all the important aspects of a patient's disease.

PMID- 1344128
TI  - Prevention of hypertension.

PMID- 1344129
TI  - Detection of cardiac chamber enlargement with the chest roentgenogram.

PMID- 1344130
TI  - Indications for thallium scanning.

PMID- 1344131
TI  - Lacunar stroke: diagnosis, evaluation, and management.

PMID- 1344132
TI  - Drug treatment of dyslipidemias: practical guidelines for the primary care
      physician.

PMID- 1344133
TI  - Update on calcium antagonists.

PMID- 1344134
TI  - Treatment of hypertensive emergencies and urgencies.

PMID- 1344135
TI  - Antiphospholipid antibodies and ischemic stroke.
AB  - Antibodies directed against phospholipids are highly associated with episodes of
      venous and arterial thrombosis, which are often recurrent. There seems to be a
      skewed frequency of cerebral thrombosis when the arterial circulation is
      affected. Clinical clues that should lead to evaluation for aPL include stroke in
      a young adult, recurrent thrombosis or miscarriage, and thrombocytopenia.
      Associated laboratory abnormalities include a biologically false-positive test
      for syphilis, abnormal antinuclear antibody titers, and a high erythrocyte
      sedimentation rate. If the activated partial thromboplastin time is prolonged on
      routine screening and does not correct with mixing studies, a lupus anticoagulant
      should be suspected. However, more sensitive and specific tests are usually
      necessary to detect aPL. Many in vitro and more recently in vivo systems strongly
      suggest that aPL may be directly implicated in the pathogenesis of thrombosis.
      Optimal management of patients with aPL-associated thrombosis is unknown. The use
      of aggressive therapeutic management schemes with such agents as warfarin or
      corticosteroids is sometimes required.

PMID- 1344136
TI  - Recognition and management of torsades de pointes.

PMID- 1344137
TI  - The resurgence of rheumatic fever.

PMID- 1344138
TI  - Peripheral arterial occlusive disease and the diabetic: current clinical
      management.

PMID- 1344139
TI  - Calcium channels in the heart: an overview.

PMID- 1344140
TI  - Genetic lipoprotein abnormalities producing high blood cholesterol.

PMID- 1344141
TI  - AHA special report discusses insurability of the adolescent and young adult with
      heart disease.

PMID- 1344142
TI  - Reducing cardiovascular diseases in blacks: evolving concepts.

PMID- 1344143
TI  - [Rectal prolapse and fecal incontinence. A prospective manometric study].
AB  - In the present work we have studied two consecutive series of patients who
      underwent a posterior abdominal rectopexy according to Wells or Ripstein. During
      the year of follow up no recurrences were observed. Functional results, evaluated
      according to a protocol, by history of the patient and manovolumetry, shoved an
      improvement of fecal continence in more than half of the incontinents in both
      series. However, constipation increased after Wells' rectopexy, while no major
      changes were observed after Ripstein's rectopexy. We conclude that the first
      surgical technique may offers worse functional results.

PMID- 1344144
TI  - [Metahemorrhagic adrenal pseudocysts: our experience].
AB  - Hemorrhagic adrenal cysts are a pathologic entity rarely described in literature.
      In this paper we present two cases of hemorrhagic adrenal cyst and we discuss
      about diagnosis and therapy.

PMID- 1344145
TI  - [The long-term complications from ileostomy in patients with Crohn's disease and
      ulcerative colitis].
AB  - In the period between 1959 and 1984 at the Surgery Department of the University
      of Goteborg, ileostomy (after colectomy) was mad in 203 patients affected by
      chronic inflammatory bowel disease. Patients were followed up prospectively to
      evaluate the frequency and severity of the complications. The cumulative rate of
      surgical reoperation was significantly higher in the group of patients with Crohn
      disease in comparison with those affected by ulcerative colitis. After 8 years it
      reached 75% in the first group and only 44% in the second. The most frequent
      indication for surgery reoperation were stenosis and retraction. 83% of the
      operations were only local not requiring laparotomy. No statistically significant
      correlation was found for the reoperation rate, the surgical technique, the
      length of the ileal resection and the post-operative weight gain. Only a
      systematic and accurate follow-up done by the surgeon and the enterostomist can
      detect an optimal functioning of the ileostomy. In case of complications which
      could be surgically corrected an early operation is needed. In most cases this
      can be simply made by local anesthesia.

PMID- 1344146
TI  - [Total thyroidectomy in recurrent goiters (anatomicosurgical observations with
      the operating microscope)].
AB  - The relapses of the multinodular goitre, often linked with an insufficient
      surgical treatment of primitive lesions, make serious problems about the
      operating technique. The current guidance of surgeons is directed towards the
      complete thyroidectomy which profits, during the operating time, by the use of
      microscope to identify and to protect the recurrent nerves. This equipment has to
      be used by those equipped which know how to use it. In our work we report the
      results obtained with this technique and it's underlined how the complete
      thyroidectomy for the benign relapsing goitre could be considered curative
      towards those cases which present hidden microcarcinoma.

PMID- 1344147
TI  - [Sexual dysfunctions after conventional proctocolectomy].
AB  - Seventy-one women who had a proctocolectomy for ulcerative colitis (n = 41) or
      Crohn's disease (n = 30) were interviewed in the follow-up clinic about
      gynaecological problems and fertility. 49% (35/71) of the women had a distressing
      vaginal discharge after proctocolectomy, compared with 9% before surgery. At the
      gynaecological examination 45% (32/71) had a heavy vaginal secretion without any
      signs of an acute vaginal infection. In 68% (30/44) fluid retention in the vagina
      was associated with a caudally firmly fixed and dilated posterior vaginal fornix.
      Twelve per cent (8/66) of the women reported dyspareunia before surgery. After
      surgery, 27% (18/66) complained of this symptom. Fertility was significantly
      reduced after surgery since only 37% (10/27) of the women who attempted to become
      pregnant succeeded within five years follow-up. The corresponding figure before
      surgery was 72% (39/54). Those who conceived went through pregnancy and
      parturition without any incident, 6 of 24 delivered by caesarean section. 57 men
      who had a proctocolectomy for ulcerative colitis (n = 41) or Crohn's disease (n =
      30) were interviewed in the follow-up clinic about the presence of sexual
      disturbances and their incidence was studied, 57% of elderly patients (above 40
      years old) complained a reduced libido and sexual satisfaction. In younger
      patients (below 40 years old) 33% complained an impaired quality of sexual ife
      and 22% complained an impaired sexual satisfaction. However, despite some sexual
      dysfunction, 56% reported improved sexual life and 67% improved sexual
      satisfaction. This may be explained by improved general health and increased
      libido after removal of diseased bowel. The incidence of patients with
      ejaculatory disfunction (retention or retrograde ejaculation) is 9%. The
      increased awareness of uro-genital disfunction and therefore their prevention can
      contribute to the improvement of quality of life and to the rehabilitation of
      patients with benign diseases.

PMID- 1344148
TI  - [Malignant peritoneal mesothelioma: its evolution and outlook].
AB  - Mesotheliomas are mesenchymal neoplasms which originate in the lining membrane of
      various serous cavities: pleural, pericardial and peritoneal. Peritoneal
      mesotheliomas are extremely rare. They are usually seen to middle to old age,
      predominate in men. We report a case and show the most recent concepts about
      histology, pathology, diagnosis and medical-surgical therapy of these diseases.

PMID- 1344149
TI  - [The functional and manometric-volumetric results following abdominal rectopexy
      for total rectal prolapse].
AB  - Functional changes after the posterior abdominal rectopexy for the treatment of
      rectal prolapse are not fully understood. We studied the effects of Wells' or
      Ripstein's rectopexy on functional characteristics as related to anal sphincter
      function, rectal volume and sensory function in 21 patients with complete rectal
      prolapse. We have observed an improvement of continence over 70 per cent in both
      groups. However, an absent or a decreased call to stool, constipation and
      evacuation difficulties are the aftermath of Wells' rectopexy, while these
      complaints appear basically unaffected by Ripstein's technique. Sensory
      thresholds for sense of filling and urge were significantly raised after Wells'
      rectopexy even one year after operation, whereas after Ripstein's operation sense
      of filling was not significantly affected and while sense of urge was increased
      early postoperatively, it was not significantly changed at one year postoperative
      control. In conclusion, when fecal incontinence appears associated to a complete
      rectal prolapse has good chances to improve postoperatively. Preoperative
      evacuation difficulties seems to be unaffected by a posterior abdominal
      rectopexy, Wells or Ripstein, but an extensive dissection of the rectum with the
      division of the lateral stalks, as it is performed in Wells' operation, seems to
      be a procedure that can create a further burden of problems to the patient and it
      seems coupled to a manovolumetric elevation of rectal sensory thresholds.

PMID- 1344151
TI  - [Phlebographic study of venous incontinence in varicose veins].
AB  - Phlebography is a test known for a long time: although by this time it is
      supported and, in a way, substituted by some substantial and not surgical methods
      like the doppler test, doppler echography, plethysmography and the duplex
      scanner. This test makes it possible for us to achieve precise diagnosis rapidly
      and in an unequivocal way, especially in those cases in which the mentioned
      methods don't give final results. Nowadays phlebography has to be optimized and
      adapted to clinical request, in order to provide a through diagnostic result. The
      purpose of this work is to evaluate the effectiveness of this methodology using a
      group of selected patients for the test.

PMID- 1344150
TI  - [The effects of unilateral spermatic cord torsion on fertility. A review of the
      literature and evaluation of the authors' own cases].

PMID- 1344152
TI  - Immune status of children suffering from minimal change nephrotic syndrome.
AB  - Twenty five children suffering from minimal change nephrotic syndrome were
      studied for immunological alterations at different stages of this disease i.e.,
      onset, relapse and remission. Changes were found mainly at onset and during
      relapse in the form of altered helper and suppressor cell ratio, depressed
      delayed cutaneous hypersensitivity reaction, decreased S-IgG bearing lymphocytes
      with low serum IgG concentration, and increased S-IgM bearing lymphocytes with
      high serum IgM concentration. Majority of these parameters returned to normal
      values during remission. Serum IgE was found high at all stages of this. These
      alterations suggest defects in cell mediated immunity resulting in secretion of
      some substance which modifies the glomerular anionic charges.

PMID- 1344153
TI  - Diagnostic parameters of vascular neoplasms by immunohistochemistry.
AB  - Immunohistochemical identification of Factor VIII-related antigen and Ulex
      Europaeus A-I lectin as endothelial markers were studied in a series of 103
      cases, comprising of benign and malignant vascular tumours, and few
      undifferentiated sarcomas. The results are correlated with that of others in this
      area and emphasizes the utility of these markers in surgical pathological
      diagnosis, especially to confirm the difficult diagnosis of angiosarcoma from
      other poorly differentiated sarcomas.

PMID- 1344154
TI  - The basics of blood cell counter.
AB  - The time has come when a traditional hematologist of a developing country needs
      to change his frame of mind from time consuming, error prone, not so precise
      manual methodologies to economical, safe and precise automated procedures. More
      important is his role as a guide and teacher for his juniors who are exposed to
      automated laboratories from the beginning of their residency. At this juncture,
      one needs to be thorough with the principles of instrumentation, different models
      available, their merits and demerits and how and where these fit with the
      requirements of the laboratory. The haematologists also must be aware that
      automation has its own problems, limitations, disadvantages and interfering
      elements. The article discusses the present state of art.

PMID- 1344155
TI  - Viral particles in persistent generalised lymphadenopathy (PGL).

PMID- 1344156
TI  - Fine needle aspiration biopsy--a critical investigation in thyrotoxicosis.
AB  - Four hundred and fifty two patients having clinical features of thyrotoxicosis
      have been studied for their hormonal (T4, T3 and TSH) content, I131 uptake levels
      and FNAB at repeated intervals. Four hundred and twenty seven had presented with
      diffuse enlargement and rest 25 cases with nodular enlargements. Of the primary
      hyperthyroidism cases 342 (82.4%) were of Grave's disease without exophthalmos
      and 73 (17.6%) with exophthalmos. T4, T3 and I131 uptake levels have correlated
      well with the degree of morphological changes as observed on FNAB. Degree of
      nuclear pleomorphism has correlated well with the duration of disease. Critical
      evaluation of morphological changes on FNAB has been done in all cases of primary
      hyperthyroidism being treated with neomercazole and radioactive iodine therapy.
      Treatment with neomercazole had shown, good correlation between time lag and the
      retrogressive changes. This was not so in cases treated with radioactive iodine
      therapy. Various known complications of radioactive treatment e.g. development of
      hypothyroidism, refractory and recurrent hyperthyroidism, exacerbation of the
      disease, radiation thyroiditis, and severe degree of dysplastic changes could be
      demonstrated in some cases on serial aspirations.

PMID- 1344157
TI  - Nucleolar organizer regions in smooth muscle and breast tumours.
AB  - Paraffin sections of formalin fixed tissues, obtained from patients with smooth
      muscle and breast tumours, were studied by the silver staining technique to
      quantitate the Nucleolar Organizer Regions (AgNORs) per nucleus and to assess its
      significance as an independent variable in predicting the behaviour of these
      neoplasms. Five benign and five malignant tumours of smooth muscle along with ten
      benign and ten malignant epithelial tumours of breast were studied. Normal
      myometrium and breast tissue served as controls. Control, benign and malignant
      tumours of smooth muscle showed mean AgNOR scores of 2.68, 3.89 and 12.50 per
      nucleus respectively. Control, benign and malignant tumours of breast showed mean
      AgNOR scores of 1.75, 7.45 and 12.72 per nucleus respectively. These results
      suggest that quantitative analysis of AgNORs per nucleus is capable of
      differentiating benign from malignant lesions of smooth muscle and breast.

PMID- 1344158
TI  - Incidence of mycoses in bronchopulmonary disorders.
AB  - A total of 274 samples were collected--180 sputum samples, 82 bronchial
      secretions and 12 pleural aspirates. Main fungus was Candida albicans from sputum
      (45.5 percent), from bronchial secretions (14.6 percent). Rest were Aspergillus,
      Alternaria and Helminthosporium. All the pleural aspirates were negative for
      fungus.

PMID- 1344159
TI  - Effect of severity of "risk region" on therapeutic intervention of myocardial
      infarction size.
AB  - Isosorbide dinitrate was tried in 27 patients of acute myocardial infarction
      (AMI) with the purpose of reduction of infarction size. Overall average effect
      was not significant. But, it was found that, the small and moderate "predicted
      infarction size" (PIS) group of patients, were benefitted by the drug therapy.
      Effectiveness in the therapeutic intervention on ischaemic injury bore an inverse
      relation with the degree of PIS or the "risk region". Varying "risk region" may
      be an important factor responsible for the apparent discrepancy between results
      of different workers regarding therapeutic intervention of infarction size.

PMID- 1344160
TI  - Photoprotection of ultraviolet light irradiated E. Coli. B/r cells.
AB  - Ultraviolet irradiated E. Coli. B/r cells recover from UV damage when the cells
      are kept in dark due to dark repair mechanism. Photoprotection by illumination of
      the cells in near UV light prior to the exposure to UV light increases the
      capacity of the cells to induce L-arabinose isomerase synthesis in response to
      inducer, L-arabinose. The survival of the cells is dependent on the UV dose. The
      increased synthesis of L-arabinose isomerase after photoprotection is due to the
      amount of cyclic AMP in the cells.

PMID- 1344161
TI  - Interstitial hydatid cyst--a case report.

PMID- 1344162
TI  - Cystic nephroma--an unusual cystic renal lesion.

PMID- 1344163
TI  - Xanthogranulomatous pseudo-tumour of vagina--a case report and review of
      literature.

PMID- 1344164
TI  - Massive xanthogranulomatous pyelonephritis--a pseudomalignant clinical entity--a
      case report.

PMID- 1344165
TI  - Cutaneous phaehyphomycosis caused by Exophiala jeanselmei var lecanii-cornii
      (Benedek and Specht) De Hoog.

PMID- 1344166
TI  - Mycotic keratitis caused by Bipolaris spicifera.

PMID- 1344167
TI  - Ultrastructural features of epithelioid tumors.

PMID- 1344169
TI  - Kala-azar in Ballia district, Uttar Pradesh.
AB  - Door to door search during 1991 in 85 villages in Ballia district of Uttar
      Pradesh revealed 29 sporadic cases of Kala-azar in four villages. Epidemiological
      investigations indicated indigenous transmission in Phulwaria village (PHC:
      Dubhar) with 25 cases while the remaining three villages showed four imported
      cases from the endemic states. No kala-azar cases had been reported in Ballia
      between 1947 and the present investigation. Phlebotomus arqentipes, the known
      vector of kala-azar in India, was encountered in 10 PHCs including the four
      villages having kala-azar cases. Regular vigilance in Ballia and the neighbouring
      districts in Uttar Pradesh bordering Bihar is suggested in view of indigenous
      transmission detected in one village with multiple infection in families. The
      presence of high vector density, ambient environmental factors and absence of
      regular residual insecticidal spray warrant constant surveillance in Kala-Azar
      prone areas in Uttar Pradesh.

PMID- 1344168
TI  - Study on the physico-chemical characteristics of breeding grounds in relation to
      the population density of Anopheles stephensi.
AB  - The present study which was based on the quarterly sampling and estimation of
      various physico-chemical factors throw light on the three significant points with
      regard to the population build up of Anopheles stephensi. Slightly alkaline pH is
      essential for higher population density, lower the salinity, higher the
      population density and higher amount of free ammonia in the water is accounted
      for the higher population density of A. stephensi.

PMID- 1344170
TI  - Importance of mean parasite clearance time and recrudescence time and their role
      in gradation of Plasmodium falciparum resistance.
AB  - The present paper describes the relationship of Mean Parasite Clearance Time
      (MPCT) and Mean Parasite Recrudescence Time (MPRT) in the epidemiology of
      Plasmodium falciparum. The role of MPCT in grading the resistance of an area has
      been discussed. Further, MPRT revealed a positive correlationship with the
      percentage of RI resistant cases, and showed an increase with age. The ratio of
      MPRT/MPCT is an indicator of stability status of the resistance.

PMID- 1344171
TI  - Record of Phlebotomus (Phlebotomus) salehi Mesghali from Barmer, Rajasthan
      (India).

PMID- 1344172
TI  - Malarial placental infection and low birth weight babies.
AB  - Two-hundred fifty-six mothers and their newborns were subjected to clinical and
      haematological tests for the evidence of malaria. Placentae of these were
      examined histopathologically for malarial parasites and malarial pigment. Forty
      six placentae showed scanty malarial pigment ingested by monocytes. These
      appearances were associated with focal syncytial necrosis and proliferation of
      cytotrophoblastic cells. Plasmodium falciparum was found in cord blood of six
      cases. The mean weight of newborns born to mothers having no evidence of malarial
      placental infection was 2.763 kg, while mean weight of newborns belonging to
      infected placentae was 2.143 kg. The difference was highly significant.

PMID- 1344173
TI  - Chromosomal translocations and inherited semisterility in the malaria vector
      Anopheles stephensi Liston.
AB  - Anopheles stephensi males were irradiated with 3500 rads of gamma rays at the
      rate of 140 rads/min to induce chromosomal aberrations. Seven reciprocal
      translocations were isolated, including four sex-linked and three autosomal. The
      presence of translocations were confirmed by cytological analysis.

PMID- 1344174
TI  - Acute respiratory infections in children: a study of knowledge and practices of
      mothers in rural Haryana.
AB  - In the present study, data were collected on knowledge and practices of mothers
      in two villages of Block Beri of district Rohtak for devising a standard
      management plan. In all 304 mothers were interviewed. About 23 per cent mothers
      recognised pneumonia by fast breathing and 11.2 per cent recognised severe
      pneumonia by chest indrawing. Only 1.3 per cent mothers knew infective origin of
      ARI. Although most of them were convinced about continuation of breast feeding,
      70 per cent of them were advising food restriction. Use of herbal tea in ARI was
      widely prevalent and so was the practice of putting warm mustard oil in ear for
      curing ear pain. Primary Health Centre was the most frequented place for
      treatment of ARI and mother-in-law was the most important person in taking
      management decisions for the child.

PMID- 1344175
TI  - Relative performance of Organon kit in comparison to Du Pont for confirmatory
      serological testing of HIV infection by western blot test in sera from blood
      donors.
AB  - A total of 32 specimens with different categories of reactivity by Du Pont
      Western Blot kit comprising of specimens showing full spectrum of HIV-I antigen
      specific bands, 19 specimens showing total absence of bands and four specimens
      showing non-specific bands (without any interpretative importance) were subjected
      to Western Blot testing by Organon test. Of the nine specimens showing full
      spectrum of bands by Du Pont the correlation with Organon kit was 100 per cent
      based on WHO criteria. Four specimens with non-specific indeterminate band
      pattern by Du Pont failed to show any band in Organon kit, indicating that latter
      to be more specific.

PMID- 1344176
TI  - Evaluation of indirect immunofluorescent antibody test for detection of IgM
      specific antibodies in malaria.
AB  - Indirect immunofluorescent antibody test using Plasmodium falciparum antigen from
      in vitro culture was evaluated for detecting IgM antibodies in order to determine
      the feasibility of its application in serodiagnosis of malaria. Test was compared
      with the already adapted IgG-IIF test using the same antigen. It was found that
      none of the healthy controls and slide negative fever cases had malaria IgM
      antibodies whereas 8 per cent of healthy controls and 49.01 per cent of the slide
      negative fever cases had malaria IgG antibodies. The sensitivity of IgM-IIF test
      was 94.68 per cent and that of IgG-IIF test was 96.81 per cent. IgM antibodies
      could be detected very early even on the first day of fever and titre rose
      gradually with increasing number of days of illness before institution of
      treatment. The IgM antibodies, being short lasting are able to reflect recent
      infection. The test although highly sensitive and specific is laborious and
      expensive. Therefore, it may be used as a serodiagnostic test in advanced
      laboratories only for confirmation of selected slide negative cases.

PMID- 1344177
TI  - Efficacy of bi-annual administration of DEC in the control of bancroftian
      filariasis.
AB  - The efficacy of bi-annual administration of DEC at the dose of 6 mg/kg body
      weight was evaluated on the microfilaraemia prevalence, density and vector
      filarial infection rates. Administration of four doses (4 x 6 mg/kg) of DEC
      significantly (P < 0.05) reduced the microfilaria rate of the community from 6.02
      per cent to 2.31 per cent, microfilaria density from 0.66 to 0.17 and infectivity
      rate of the vector population from 0.8 per cent to 0.39 per cent.

PMID- 1344178
TI  - Status of lymphatic filariasis in some select slum clusters of Delhi.
AB  - Filaria surveys conducted in some select slum clusters namely Hari Nagar, Yamuna
      pusht near Vijaya Ghat along the Ring Road and Timarpur in Delhi during 1989,
      1991 and 1992 respectively, covering a population of approximately 5000 slum
      dwellers revealed the presence of bancroftian microfilaria (mf) carriers and
      disease cases. The mf and disease rates (per cent) in these three slum areas were
      in the order of 6.3, 2.2, 3.7 and 1.4, 0.5 and 0.1 respectively. The mf density
      varied from 3.1 to 12.3 per 20 cumm. blood. High ten man hour densities of Culex
      quinquefasciatus (581) in Yamuna pusht followed by (355) in Timarpur were
      recorded during entomological investigations. Hari Nagar accounted for least ten
      man hour density of Cx. quinquefasciatus (160), because collection was made
      during winter months (November-December). The dissection of Cx. quinquefasciatus
      did not reveal any human filarial infection except in Yamuna pusht where out of
      139 only one Cx. quinquefasciatus was found infective.

PMID- 1344179
TI  - Critical appraisal of entomological data of Madhya Pradesh for 1991 and its
      relevance to the National Malaria Eradication Programme.
AB  - Entomological data generated in five entomological zones, of Madhya Pradesh State
      during 1991 including, Bhopal, Bilaspur, Gwalior, Indore and Raipur were
      analyzed. The entomological parameters that were studied included per man hour
      (pmh) density, abdominal physiology and parity status. The inferences were
      related to i) resting behaviour (exophily/endophily) ii) duration of indoor
      resting period of mosquitoes iii) man-vector contact iv) efficacy of residual
      insecticide and v) vulnerability of the area to focal malaria outbreaks. The data
      chiefly pertains to the putative malaria vector Anopheles culicifacies in all the
      five zones under study. The studies have brought out that A. culicifacies,
      traditionally endophilic and endophagic, has demonstrated radical departure in
      its resting and feeding behaviour. In Gwalior zone the species shows high
      preference for exophily. In Bhopal and Indore zones there is differential resting
      behaviour with respect to season. The species shows, for most part of the year
      exophily but is also endophilic during post monsoon period. In Bilaspur zone the
      species shows marked exophily and endophagy. Irrigation practices seem to have
      affected the mosquito population density patterns in these regions as brought out
      in Indore and Bilaspur zone, where high density pattern is observed between
      November and February. These findings have obvious implications in selecting the
      appropriate intervention methods and the period of spray in areas where residual
      spray is the method of choice for interruption of transmission.

PMID- 1344180
TI  - Annual report on findings of infectious agents in Japan 1991.

PMID- 1344181
TI  - [The correlation between the conventional spermogram parameters and the osmotic
      resistance tests in patients from among fertile and infertile couples].
AB  - It is well accepted that routine semen analysis is a useful tool for valuation of
      male potential fertility. In our environment, HOST has been recently applied as
      an additional approach which early detects structural and/or functional
      alterations of the sperm membranes. We investigated the possible relationship
      between some semen parameters and HOST in males from A) fertile couples (23-32
      years old; n = 11) and B) sterile couples (25-35 years old; n = 171. Sperm
      concentration, motility, morphology and HOST (semen incubation in hypoosmotic
      saline solution-sodium citrate and fructose, 150 m0sm/1--, 37 degrees C during 60
      min) were evaluated. In HOST determinations, results higher than 60% of swollen
      cells are considered within the normal range. In our study, sperm from males of B
      group showed a significantly lower percentage of hyperhydrated cells than those
      from A group (55.7 + 2.2% and 70.4 + 2.3% respectively; p < .001). In addition, a
      significant statistical correlation between HOST vs motility or normal morphology
      was found. On the contrary, we detected no correlation between HOST vs sperm
      concentration or volume. We suggest that development and application of HOST as a
      routine, can play an important role in the evaluation and prognosis of an
      infertile couple.

PMID- 1344182
TI  - [Alternatives for closure of the rectal "stump" in Hartmann's operation. A
      comparative experimental study which includes the resorbable mechanical suture
      (polysorb)].
AB  - Five different kinds of sutures which can be used for closure of the rectal stump
      in Hartmann's operation are evaluated in the same animal. They are compared at
      six different phases of the cicatrization process: 7-30-45-60-90 and 150 days. In
      the analysis, the degree of complete cicatrization is considered as well as the
      thickness of the cicatriced tissue, and other factors such as persistence of
      suture material and the result of it. All of the sutures involved accomplished
      the goal of a good joint of the planes of intestinal suture. Although, two of
      them, the metal stapler and Polyglactin (Vicryl) in extramucosal surgery fulfill
      almost in an ideal way the goals concerning security, rare reaction to suture
      material, and consequently less thickness in the cicatriced tissue (2 x 2 and 1 x
      1 mm respectively) as well as complete cicatrization in ninety days. Stapler is
      performed quicker and in a more aseptic way, but the scar resulting from
      Polyglactin is smaller. In separate extramucosal points, silk produces a more
      important tissue reaction with a thicker scar (3 x 3 mm) coming to an end in 150
      days. "Albert Lembert" type suture is really far away from being a good mean
      because it creates an important tissue reaction with a thick scar (3 x 3 mm),
      with late consolidation (150 days) and granulomatous reaction. Resorbable stapler
      -Polisorb--has a considerable volume and it causes an important tissue reaction
      which determines a very thick (4.5 x 4.5 mm) and "unfinished" scar within 150
      days; really far away for practical use.

PMID- 1344183
TI  - [The configuration of a video signal digitalizing system used in astronomy for
      radiological applications].
AB  - A digital system of video signals of astronomical use was developed to be applied
      in the field of radiology. The images were obtained from radiologic films by
      means of a standard video camera. The minimal specifications of the digital
      images for use in radiology are as follows: a) 2.5 lpm spatial resolution, b) a
      digital resolution of 8 bits (256 gray levels). Images (194 by 154 mm in size)
      can be obtained. The software processing was adapted for treatment of the images
      in radiology.

PMID- 1344184
TI  - [The intraepithelial mucous glands in the oral cavity of Myiopsitta monacha (the
      parrot or common parakeet)].

PMID- 1344185
TI  - [Perforated colonic diverticulitis: its diagnosis and treatment. Our experience].
AB  - Six cases of perforated diverticulitis are presented that needed urgency surgery.
      The objective is to consider our guides of diagnosis and treatment towards this
      pathology and to justify Hartmann's operation as the technique of choice for
      these cases of generalised peritonitis.

PMID- 1344186
TI  - [The prevalence of spinal column pathologies. Preventive measures].
AB  - It has been observed that a high percentage of students present problems with the
      spinal column; this is due to the lack of prevention in the activities of daily
      life and in hospitals' practice. Added to this, is the presence of a large
      percentage of alterations of the feet. This coincides with our hypothesis of
      work, and brings us to suggest the correct positions in the principal postures.

PMID- 1344187
TI  - [The Department of Medical Sciences. A synthesis of its beginnings and evolution
      in the Universidad Nacional de Cordoba].

PMID- 1344188
TI  - Structural changes induced by He-Ne laser on the chick embryo ovary.
AB  - The morpho-histochemical alterations that occur in the chicken ovary at 7 days of
      incubation after irradiation with He-Ne laser of a potency of 5 mw and at a
      wavelength of 632.8 nm were studied. The embryos were irradiated for 5 minutes
      through a window opened in the eggshell and aseptically maintained in incubator
      for 24 hours. The gonads were dissected out and processed for the following
      techniques: H/E, PAS, alcian blue, and toluidine blue. CONTROLS: The ovaries were
      formed by a germinative or superficial epithelium, with germ and epithelial
      cells, and by primary sex cords compressed between them, although separated by a
      reduced stroma. The cords contained germ cells The surface coat of the
      germinative epithelium presented a thin layer of PAS positive, alcianophilic at
      pH 25 and orthochromatic material. Basement membranes and intercord extracellular
      substance were also PAS positive. PROBLEMS: Disorganization of the tissue
      structure was well manifest in irradiated gonads, accompanied by negativization
      of the histochemical reactions. A lymphocytic infiltration was also found. No
      structural alterations were observed in germ or epithelial cells. It is concluded
      that laser radiations would act producing decrease of the mucosubstances
      associated to the plasma membrane and basement membrane. They would also provoke
      the appearance of an inflammatory mononuclear infiltration.

PMID- 1344189
TI  - Initiation of dialysis: when?
AB  - Initiation of dialysis depends upon several parameters including medical and non
      medical reasons. Among the medical parameters measured or calculated creatinine
      clearance from plasma creatinine concentration seems to be the most reliable
      factor although clinical parameters such as gastro-intestinal disorders,
      cardiovascular, hematological, neurological manifestations and last but not least
      general status of the patient tend to play a determinant role in the decision of
      initiating dialysis. Dialysis is usually initiated for patients with a normalized
      creatinine clearance of 5 ml/min.1.73 m2 but optional dialysis could be initiated
      from a normalized creatinine clearance of 10 ml/min.1.73 m2, in case the
      capability of the patient and the physician to tolerate the burden of uremic
      syndrome is overcome. Rather than employing dialysis too late, it now seems
      advisable to initiate dialysis earlier in the course of chronic renal failure.
      Actually, retrospective analysis of 167 over 625 cases records from 1981 to 1985
      and of 178 over 700 case records from 1986 to 1990 in the Department of
      Nephrology, Necker Hospital, plasma creatinine concentration at initiation of
      dialysis of the two period was 1044 +/- 17 and 981 +/- 13 mol/L respectively,
      corresponding to a creatinine clearance of 6 and 7 ml/min. It is clear now that
      management of chronic renal failure patients should be considered as a whole and
      initiation of dialysis is the end point of this global strategy. Definitely,
      optimal time for initiating dialysis should take into account various parameters,
      both biological and clinical as well as associated parameters such as age of the
      patient and involved systemic disease.

PMID- 1344190
TI  - Sinus node automaticity during atrial fibrillation in isolated rabbit hearts.
AB  - BACKGROUND: It is still unclear what role the sinus node may play in the genesis
      or perpetuation of atrial fibrillation. Therefore, we studied the electrical
      activity in different regions of the sinus node during atrial fibrillation.
      METHODS AND RESULTS: In Langendorff-perfused rabbit hearts, paroxysms of atrial
      fibrillation were induced by burst pacing. Standard microelectrode techniques
      were used to record transmembrane potentials from different regions of the sinus
      node. We found that during atrial fibrillation, a high degree (5:1) of sinoatrial
      entrance block was present that protected the pacemaker fibers in the center of
      the sinus node against the high rate of fibrillatory impulses. As a result, the
      true pacemaker fibers in the center of the node were activated with only a
      slightly higher average rate than during sinus rhythm. Spontaneous diastolic
      depolarization was still present but was modulated by electrotonic
      depolarizations due to intranodal conduction block of atrial fibrillatory
      impulses. Incidentally, phase 4 depolarization resulted in the generation of
      spontaneous action potentials in the sinus node. However, the high activation
      rate in the sinoatrial border during atrial fibrillation prevented these
      spontaneous impulses to exit from the sinus node. Because of the minimal degree
      of sinus node overdrive suppression (9%) and the presence of concealed
      automaticity during atrial fibrillation, spontaneous termination of atrial
      fibrillation was promptly followed by resumption of normal sinus rhythm.
      CONCLUSIONS: During atrial fibrillation, sinus automaticity still is present in
      the center of the sinus node and hardly overdrive suppressed due to a high degree
      of sinoatrial entrance block.

PMID- 1344191
TI  - [Aldose reductase: physiological role, properties and prospects for regulating
      activity].
AB  - Some properties of aldose reductase isolated from various sources and possible
      ways of regulation of the enzyme catalytic activity are reviewed. Mammalian
      aldose reductases are monomeric enzymes with M(r) of 30-40 kDa and a broad
      substrate specificity towards aldoses. The physiological role of this enzyme
      consists, apparently, in providing an additional pathway for utilization of
      glucose and removing toxic compounds carrying an aldehyde group from the cell.
      Aldose reductase is thought to play a key role in various hyperglycemic states,
      including diabetic cataract. The kinetics of the aldose reductase reaction is
      hyperbolic with NADPH and nonhyperbolic with glucose. The rate of the enzyme
      catalyzed reaction is determined by the effector binding in the active of
      inhibitory center of the enzyme. Incubation with substrates leads to the
      activation of the enzyme which is accompanied by a decrease of the effector
      binding in the enzyme inhibitory center with a sharp decrease in the sensitivity
      of the activated enzyme to NADPH concentration changes in the presence of glucose
      excess. A mechanism underlying the catalytic effect of both native and activated
      forms of the enzyme is proposed.

PMID- 1344192
TI  - [Effect of thyroid hormones and diacylglycerols on sphingomyelin metabolism in
      liver cell nuclei in rats of various ages].
AB  - Sphingomyelin metabolism in liver cell nuclei of rats of various age has been
      studied. It was found that the level of sphingomyelin hydrolysis in cell nuclei
      is the highest in young animals, showing a decrease in 24-month-old animals. The
      age-specific fluctuations in the activity of phospholipase C may be one of
      possible reasons for sphingomyelinase activity changes in liver nuclei during
      ontogenesis. It has been shown that thyroid hormones and diacylglycerols control
      the sphingomyelinase activity in rat liver cells.

PMID- 1344193
TI  - [Regulation of aldose reductase activity. Mechanism of action of an activated
      form of the enzyme].
AB  - Activation of bovine eye lens aldose reductase during its incubation with NADPH
      and glucose was studied. The activated form of the enzyme was isolated, and the
      rate of glucose reduction measured within a broad range of substrate
      concentrations. Spectrophotometric titration and equilibrium gel-filtration were
      used to study the interaction of the enzyme active center with substrates. It was
      found that the reaction kinetics obeys the mechanism of a quasi-equilibrium
      binding of substrates with isomerization of the enzyme complexes with
      nicotinamide dinucleotide phosphates. This activation is accompanied by a
      transition from non-ordered to highly ordered binding of the substrates. The
      effect of ligands in the catalytic and inhibitory centers of the activated enzyme
      on the catalytic reaction was examined. It was found that the activated form of
      aldose reductase is characterized by a lower affinity of the inhibitory center
      for the flavonoid, morin. Morin binding not only inhibits the reaction but also
      prevents the activation of the enzyme.

PMID- 1344194
TI  - [Nonenzymatic reduction of methemoglobin by free radical forms of NADH and
      riboflavin].
AB  - Nonenzymatic reduction of methemoglobin (met-Hb) is effectively catalyzed by NADH
      and riboflavin (RF). At low concentrations of met-Hb the EPR spectra of the
      ternary complex are characterized by an increased, whereas those at high met-Hb
      concentrations--by a decreased intensity of the RF semiquinone signal, which
      suggests that the met Hb reduction by a Leu-form of RF proceeds at a higher rate
      than that by the RF semiquinone radical. Riboflavin also accelerates the met-Hb
      reduction by a NADH-Fe2+ or NADH-Fe(2+)-EDTA mixture. It was found that the rate
      of met-Hb reduction by the organic radical increases in the following order: NAD.
      < RF H. < RF H2.

PMID- 1344195
TI  - [Comparative characteristics of cyclodextrin glycosyltransferases from various
      groups of microorganisms].
AB  - Cyclodextrin glycosyltransferases (CGT-ase, 1.4-alpha-glucanotransferase,
      cyclizing, EC 2.4.1.19) produced by some thermophilic, alkalophilic and
      mesophilic bacterial strains, were isolated and characterized. It was shown that
      thermophilic and mesophilic CGT-ases represent a mixture of alpha-, beta- and
      gamma-cyclodextrins (CD), alpha-cyclodextrin being the predominant component.
      Alkalophilic enzymes produce only beta-CD and are able to produce CD not only
      from starch but also from maltose, melibiose, maltotriose, amylose and
      amylopectin. The optimal conditions for the catalytic activity of the enzymes
      were determined. It was found that calcium, magnesium and zinc ions have a
      beneficial effect on the specific activity of these enzymes. The amino acid
      composition of the enzymes was studied.

PMID- 1344196
TI  - [Kinetics of merthiolate-induced aggregation of human platelets].
AB  - Incubation of human platelets (in the form of platelet rich plasma or washed
      platelet suspension) with sodium merthiolate (ethyl mercuric salicylate
      inhibiting the arachidonic acid incorporation into phospholipids) induces their
      irreversible aggregation, which is accompanied by TxB2 synthesis. The merthiolate
      induced aggregation has a lag-period of 0.5-10 min, whose magnitude is inversely
      correlated with the merthiolate concentration. The concentration dependencies of
      the rate of the merthiolate-induced and arachidonate-induced aggregation are
      threshold ones; the Hill coefficients are more than 30. The merthiolate-induced
      aggregation occurs in two phases: a slow phase which is independent of the
      arachidonic acid cyclooxygenase metabolism and a fast phase which is fully
      blocked by indomethacin. This aggregation is inhibited by PGE1 and ajoene (an
      inhibitor of the fibrinogen interaction with the fibrinogen receptor,
      GPIIb/IIIa). Quantitative and qualitative analyses of the experimental data were
      performed, using a model which took account of: (a) increase in the concentration
      of free endogenous arachidonic acid resulting from the inhibition by merthiolate
      of the arachidonic acid re-incorporation into phospholipids, and (b) existence of
      a threshold intracellular arachidonic acid concentration needed for the
      irreversible aggregation of platelets.

PMID- 1344197
TI  - [Monomerization of the fragment D dimer of stabilized fibrin by a secretion from
      the medicinal leech salivary gland].
AB  - The salivary gland secretion of the medicinal leech catalyzes the conversion into
      monomeric form of the fragment D dimer, the product of limited proteolysis of
      stabilized fibrin. Analysis of N-terminal sequences revealed identical fragments
      for the D-dimer gamma-gamma-chains and the D-monomer gamma-chains formed via this
      reaction and established the presence of only one N-terminal amino acid (Ser).
      These results provide evidence for the preservation of integrity of the
      polypeptide chains during monomerization of the D-dimer.

PMID- 1344198
TI  - [Myc proteins, prothymosin alpha, and cell division].

PMID- 1344199
TI  - Unusual dementias. Introduction.

PMID- 1344200
TI  - Neuropathology of unusual dementias: an overview.

PMID- 1344201
TI  - Familial Alzheimer's disease.

PMID- 1344202
TI  - Pick's disease.

PMID- 1344203
TI  - Frontal lobe degeneration of non-Alzheimer type.
AB  - In a longitudinal prospective study of dementias, several hundred cases have been
      examined from a clinical, brain imaging, neurochemical and neuropathological
      point of view. Frontal lobe degeneration of non-Alzheimer type (FLD) was the
      second most common primary degenerative dementia found in about 10% of the
      material. FLD has a consistent pathology and a characteristic clinical picture,
      which have been described by several independent research groups. The cortical
      degeneration mainly involves frontal or frontotemporal grey matter, without the
      circumscribed or knife-blade atrophy seen in Pick's disease. The degeneration
      involves predominantly frontal areas, including the insula and cingulate gyrus in
      its anterior parts. The striate body is normal or only slightly altered. The
      pathological changes are non-specific, with neuronal loss, slight gliosis and
      spongiosis but none or few senile plaques, tangles, congophilic vessels or Pick
      cells. Pathological changes are in some respects similar to those in amyotrophic
      lateral sclerosis. FLD is a slowly progressive dementia with personality changes,
      lack of insight, disinhibition, stereotypy and later apathy. There is also
      progressive dynamic aphasia which ends in mutism and amimia. Memory, spatial
      ability and receptive language functions are comparatively spared. Psychotic
      symptoms, emotional reactions, hypochondriasis and a Kluver-Bucy-like syndrome
      are sometimes observed. Electroencephalography is normal, at least during the
      early stage, while functional brain imaging such as regional cerebral blood flow
      reflects the frontal pathology. It is possible to achieve early diagnosis and
      differentiation from Alzheimer's disease and cerebrovascular dementia by clinical
      examination with neuropsychological assessment supported by brain imaging, and in
      the future probably various biological markers. The aetiology is unknown but
      there is a positive family history for dementia of similar type in about 50% of
      post-mortem verified cases.

PMID- 1344205
TI  - Dementia with motor neurone disease.

PMID- 1344204
TI  - Spectrum of primary progressive aphasia.

PMID- 1344206
TI  - Human prion diseases.

PMID- 1344207
TI  - Lewy body dementia.
AB  - Lewy body dementia is common. It presents either with cognitive impairment and
      neuropsychiatric disturbance followed by parkinsonism or as dementia complicating
      established Parkinson's disease. It is unusual both in its pathological features
      and in its clinical manifestations. Although both overlap to some extent with
      those of Alzheimer's disease, Lewy body dementia is at least potentially
      recognizable during life. Some of its manifestations can be ameliorated by
      established methods, and it has pathological and neurochemical features which
      offer some hope for the development of useful palliative therapy. Major progress
      towards effective treatment is, however, likely to depend upon an improved
      understanding of the molecular mechanisms underlying its aetiology.

PMID- 1344208
TI  - Corticobasal degeneration.

PMID- 1344209
TI  - Dioxin risk assessment for human health: scientifically defensible or fantasy?

PMID- 1344210
TI  - Nonresponsiveness of the rat liver to alkylating carcinogens given by gavage.
AB  - Carcinogenic alkylating agents administered orally are metabolized in the liver
      and alkylate DNA in liver cells of rats and hamsters. They frequently, but not
      always, induce liver tumors, in addition to tumors of other organs. Directly
      acting alkylating agents, such as alkylnitrosoureas and alkylnitrosocarbamates,
      rarely induce liver tumors, although they alkylate DNA in liver cells. The
      methylating agents nitrosodimethylamine and azoxymethane induce high incidences
      of liver tumors in rats when given in drinking water, but few or no liver tumors
      when given by gavage, although the total dose and the weekly dose were the same
      in either regimen. In contrast, methylnitrosoethylamine and nitrosodiethylamine
      give rise to liver tumors in rats in high incidences whether given by gavage or
      in drinking water. Sharp differences are also observed with other nitrosamines,
      such as those containing a propyl group with an oxygen substituent in the 2
      position. These discrepancies indicate that, in addition to alkylation of DNA,
      pharmacokinetics of dosing and distribution and other reactions of the carcinogen
      are the dominant factors in determining the development of tumors in the liver.

PMID- 1344211
TI  - Caloric restriction and chemical toxicity/carcinogenesis.

PMID- 1344213
TI  - Abstracts of papers presented at the Annual Meeting of the Society of Quality
      Assurance: Visions for the 90s. Kansas City, Missouri, October 15-18, 1991.

PMID- 1344212
TI  - QSARs for monosubstituted phenols and the polar narcosis mechanism of toxicity.
AB  - Eighty 2-, 3-, and 4-position monosubstituted phenols representing various
      substituents were evaluated for relative toxicity, log IGC50(-1), with a short
      term static protocol in the Tetrahymena population growth inhibition bioassay.
      Quantitative structure-activity relationships (QSAR) were examined using the 1
      octanol/water partition coefficient (log K(ow)) and ionization constant (pKa) as
      independent variables. Four derivatives did not elicit the measured response at
      saturation. Five derivatives revealed altered high-performance liquid
      chromatography spectra with time. None of these derivatives were included in QSAR
      development. In addition, the carboxyl and nitroso derivatives were detected as
      statistical outliers. The model log IGC50(-1) = 0.6655 (log K(ow)) - 0.1464 (pKa)
      + 0.2206, n = 67, r2 = 0.909, s = 0.212, was found to be an excellent predictor
      of activity of phenols which elicit their toxic response by the polar narcosis
      mode of action. For the most part the tested derivatives showed little abiotic
      loss over the duration of the bioassay.

PMID- 1344214
TI  - Regulation of existing chemicals under TSCA: information disclosure as the route
      to reducing risk and increasing available data.
AB  - The Toxic Substances Control Act (TSCA) empowers the Environmental Protection
      Agency (EPA) to regulate risk associated with the use of existing chemicals and
      the introduction of new chemicals into commerce. Due to a number of concerns,
      however, the authority to regulate existing chemicals under TSCA has enjoyed
      limited success. A more generic and flexible approach is needed to achieve
      significant risk reduction for existing chemicals. This paper presents a frame
      work for a generic approach to the regulation of existing chemicals. Under this
      framework, EPA would officially recognize that the distribution of chemical
      substances without evaluating and communicating to the user how to avoid
      operationally undesirable exposures represents an unreasonable risk to health or
      the environment. Acting under the authority of TSCA, EPA would then generically
      require suppliers to communicate acceptable exposure levels and information
      regarding safe use. This framework is consistent with the express policy of TSCA,
      which states that development of data with respect to the effects of chemical
      substances and mixtures on health and the environment should be the
      responsibility of manufacturers and processors of chemicals. The approach
      outlined here is consistent with and complements initiatives of the Office of
      Toxic Substances (OTS) and would enable OTS to accomplish some of the fundamental
      goals of TSCA.

PMID- 1344215
TI  - The health effects of dioxin on humans.

PMID- 1344216
TI  - Emergency exposure limits: a guide to quality assurance and safety.
AB  - Emergency exposure limits (EELs) are necessary in disaster prevention,
      preparation, and repression. Occupational EELs are available for many chemicals,
      but are of low toxicological adequacy. An animal experimental EEL of high
      toxicological adequacy available for many irritant chemicals is the concentration
      causing a 50% decrease in respiratory rate (RD50). The most outstanding EELs for
      the general population are the emergency response planning guidelines (ERPGs). A
      theoretical framework for a three-limit system is developed by the European
      Chemical Industry Ecology and Toxicology Center (ECETOC). ECETOC found over one
      order of magnitude variation between assessments of several companies. Nine
      selected EELs were classified in three clusters of increasing degrees of
      seriousness of health effects. There was little consistency within clusters,
      making it impossible to combine EELs. It is recommended to develop a
      toxicologically adequate EEL in an intercontinental context with cooperation of
      industry and (supra)national regulatory bodies. ERPGs can be taken as a start.
      The framework developed by ECETOC can be used to improve the limit setting
      procedure. A 5- to 10-year update should become part of the procedure. Attention
      should be devoted to the use of expert judgment. The minimal uncertainty in EELs
      should be expressed by presenting ranges instead of single values.

PMID- 1344217
TI  - A quality process for chemical product risk assessment.
AB  - One cannot manage a health or environmental risk of unknown dimension. Thus, the
      rational and cost-effective control of any risk lies first in its reasoned
      assessment. The assessment of risk is a scientific endeavor which embodies the
      intellectual use of information to reach a determination or assignment of an
      ascribed level of danger. It is, however, a decision process and approach whose
      details are substantially value laden. As such, it is potentially subject to a
      myriad of subjective interpretations from individuals with special interests and
      perspectives. Given this nature, it is incumbent upon those responsible for risk
      assessment in any organization to formulate a broad-based scientific consensus
      regarding the principals of quality assurance for the risk assessment process in
      their organization. This paper attempts to outline a rational and prudent
      consensus-based system for the quality assurance of risk assessment concerned
      with the danger to human health and the environment posed by the use of chemical
      products. We present it as a model that we hope could be accepted and
      implemented.

PMID- 1344218
TI  - Lectin binding patterns in benign and malignant lesions of the breast.
AB  - The binding patterns of a panel of eight lectins were studied in twenty eight
      breast lesions, consisting of ten cases of fibroadenoma, three cases of
      cystosarcoma phyllodes, five cases of fibrocystic disease and ten cases of
      infiltrating duct carcinoma by light microscopy. The eight lectins viz. PNA, WGA,
      RCA, SBA, UEA I, LTA, LCA and Con A were tested on paraffin sections using the
      Avidin Biotin Peroxidase Complex technique. PNA, RCA and UEA I showed a
      consistent positivity in benign and malignant lesions. The binding was localised
      mainly along the apices of mammary ductal epithelial cells in the benign lesions.
      In contrast, the malignant cells showed a considerable variation in staining
      patterns like diffuse cytoplasmic, membranous, and vacuolar. No definite
      correlation was seen between the intensity of binding and the histological grade
      in infiltrating duct carcinoma except in the case of Con A which was seen to bind
      more intensely to poorly differentiated tumours. The diagnostic significance of
      these patterns have been discussed.

PMID- 1344219
TI  - Clinical utility and monitoring of breast cancer by circulating immune complexes.
AB  - Circulating immune complexes (CIC) were estimated in 22 patients of breast
      carcinoma, 25 healthy control volunteers and 10 follow-up cases after mastectomy
      by polyethylene glycol precipitation (PEG pptn) test and Latex agglutination
      inhibition (LAI) test. CIC levels increased with advancing stage of breast
      carcinoma. Significant increase in CIC levels was observed in stage II (p <
      0.01), followed by highly significant increase in stage III and IV (p < 0.01) as
      compared to the control group. Sharp decrease in CIC levels was observed three
      months after radical surgery in 9 post-operative patients. One patient remained
      seropositive by both tests, followed by a fatal outcome after four months follow
      up. Seropositivity for CIC by PEG pptn test in patients of breast carcinoma was
      72.72 percent as compared to 81.81 percent by LAI test. Combination of both tests
      increased total CIC positivity by 90.9 percent. Clinical utility and prognostic
      significance of CIC in monitoring breast carcinoma patients has been demonstrated
      by our study.

PMID- 1344220
TI  - Myocardial changes in neonates dying of asphyxia neonatorum.
AB  - Ten neonates, asphyxiated at birth, were studied by Apgar score, ECG ischaemic
      score grading (ECGisg), Cardiothoracic (CT) ratio, biochemical parameters like
      CPK, CPK-MB fraction during life; and they were subjected to postmortem study
      with particular attention to the changes in the heart. The study revealed that 7
      out of 10 asphyxiated neonates showed variable evidences of myocardial damage;
      but the extent of damage though well correlated with biochemical parameters, did
      not correspond well with the extent of asphyxia and the survival period. In rest
      3 cases, myocardial damage was not overt though there was evidence of asphyxia
      and evidence of myocardial damage in the form of elevated CPK-MB level. These
      patients probably had died of "Biochemical Lesion" as described by Rudolf Peter.

PMID- 1344221
TI  - Effect of H37Ra on PHA-induced migratory inhibition of leucocytes in patient of
      tuberculosis.
AB  - Eighty nine cases of active pulmonary tuberculosis were classified into four
      stages depending on the clinical extent of disease. Leucocyte migration
      inhibition test (LMIT) was done using mitogen phytohaemagglutinin (PHA) and H37Ra
      specific antigen. Normal PHA responses were observed in all clinical stages while
      specific immune response in relation to inhibition of leucocyte migration
      decreased from stage I to stage IV. Effect of H37Ra on PHA induced release of
      lymphokine was studied by mixing the two and comparing the percentage migratory
      inhibition of the mixture with that of PHA alone. Increased or decreased values
      with mixture compared to those with PHA alone were regarded as enhancement or
      inhibitory effect respectively. Median percentage effect of H37Ra on PHA induced
      migratory inhibition was found to be inhibitory in first three stages and
      controls while enhancement effect was observed in stage IV. A total of 22 cases
      in all stages showed enhancement effect while 48 cases showed inhibitory effect.
      The possible mechanism of enhancement or inhibitory effect are discussed.

PMID- 1344222
TI  - Glomerular alterations in idiopathic haematuria--ultrastructural and morphometric
      analysis.
AB  - Re-evaluation of kidney biopsies has been done along with morphometric analysis
      of glomerular basement membrane thickness (G.B.M.) in 41 cases of idiopathic
      haematuria, in whom the initial routine light, immunofluorescent and electron
      microscopic examination had not shown any significant alterations. Extreme
      attenuation of G.B.M. (mean thickness of 2581 +/- 488 A) had been found in thirty
      one patients in contrast to mean GBM thickness of 4295 +/- 470 A found in control
      group. Absence of any history of familial haematuria in these patients
      distinguished them from hereditary nephropathies and hence categorized under the
      term thin basement membrane nephropathy. Follow up of these patients for upto 8
      years had shown persistence of symptoms without further deterioration of renal
      function as well as morphology.

PMID- 1344223
TI  - Fine needle aspiration cytology (FNAC) in the diagnosis of solid renal masses--a
      study of 92 cases.
AB  - Percutaneous fine needle aspiration cytology (FNAC) was employed as preoperative
      diagnosis in 92 solid renal masses from June, 1984 till December, 1990.
      Ultrasonography guided FNAC was employed in 26 lesions. There were 79 malignant
      tumours, 3 benign tumours, 6 lesions were inflammatory and only necrotic material
      was seen in 4 cases. Correlation with histopathology showed diagnostic accuracy
      of 91.3%. There were two false positive reports. No complication was encountered
      in this study.

PMID- 1344224
TI  - Meningococcal meningitis in Ludhiana.
AB  - A retrospective study was carried out at Dayanand Medical College & Hospital,
      Ludhiana (Punjab) during the period from January 1985 to June 1990 to know the
      incidence of meningococcal meningitis. Meningococcal etiology was established in
      170 (49.41%) cases out of 344 cases of bacterial meningitis. Out of 170 cases of
      meningococcal meningitis, 74 (43.52%) were positive only by smear examination, 90
      (52.94%) were positive both by smear as well as culture and there were six
      (3.52%) cases which were positive only by culture. The organisms were sensitive
      to most of the common antibiotics including penicillin, chloramphenicol,
      ampicillin and sulphadiazine.

PMID- 1344225
TI  - Present phage types and antibiotic susceptibility of salmonellae.
AB  - A total of 168 strains of Salmonella were isolated in the Command Pathology
      Laboratory (WC) Delhi Cantt during the year 1990. Out of this, 143 were
      Salmonella typhi, 17 Salmonella paratyphi A, 7 Salmonella typhimurium and 1
      Salmonella manhattan. The commonest phage type and biotype of Salmonella typhi
      was type E1 and type 1 respectively. The dominant biotype of Salmonella paratyphi
      A was type I. There was a very high degree of multidrug resistance of most of the
      strains. But all the strains were sensitive to ciprofloxacin and norfloxacin.

PMID- 1344226
TI  - Testicular proteins and DNA in experimental fluorosis.
AB  - Experimental fluorosis was induced in young male albino rabbits by exposing them
      to 0, 5, 10, 20 and 50 mg of NaF via subcutaneous injections for a period of 3
      1/2 months. The testicular structural, nuclear and total proteins were
      significantly depleted in all test groups of animals as compared to the control.
      There was a significant (p < 0.001) reduction in the testicular DNA after drug
      administration. The relevance of these results in experimental fluorosis has been
      discussed.

PMID- 1344227
TI  - Bacterial flora of the endometrium in infertile women from Manipal.
AB  - Endometrial curettage specimen culture of 140 infertile women showed 64 (45%)
      organisms. Mycobacterium tuberculosis 8 (5.7%) and Anonymous mycobacteria 14
      (10%) were the commonest organisms isolated. Among the anonymous mycobacteria,
      following species were isolated M. scrofulaceum 10, M. kansasii 2, M. fortuitum
      2. Gram positive and gram negative organisms were isolated from 42 (30%)
      specimens of the endometrium; 76 (54%) of the endometrium specimens were sterile.

PMID- 1344228
TI  - Cervical hibernoma (report of a case of fine needle aspiration cytology) with
      subsequent biopsy.

PMID- 1344229
TI  - Non-infectious granulomatous angiitis of central nervous system--an autopsy
      report.

PMID- 1344230
TI  - Adenocarcinoma of the colon in children and adolescents--report of three cases.

PMID- 1344231
TI  - Intramuscular myxoma--a report of two cases with review of literature.

PMID- 1344232
TI  - Acute renal failure in multiple myeloma--a pathological study.

PMID- 1344233
TI  - Cysts of the spleen--a report of seven cases.

PMID- 1344234
TI  - Nutritional modulation of immunity to infection.
AB  - PEM of varying grades constitutes an important nutritional deficiency disorder of
      young children. Several immune mechanisms are found to be impaired in severely
      malnourished children thus making them victims of the vicious cycle of infection
      and malnutrition. Early impairment of neutrophil function triggers the vicious
      cycle and this emphasizes the need for prevention and early treatment of acute
      infections in children. Often based on the observations made in severely
      malnourished children, doubts have been expressed about the success of
      vaccination programmes in communities where malnutrition is widespread. But the
      humoral and cell mediated immune responses which are essential for adequate
      response to the various vaccines are found to be satisfactory among the
      undernourished children who constitute the major segment of the beneficiaries of
      such programmes in the communities. These observations help in strongly
      recommending the implementation of vaccination programmes in such communities and
      thus prevent severe malnutrition. Severe malnutrition, though often amenable for
      rehabilitation in the hospital, however, leaves certain permanent immunological
      sequelae and thus prevention of severe PEM in young children is important.

PMID- 1344235
TI  - [The safety of geriatric anesthesia].
AB  - Perioperative abnormalities and complications were reviewed in 556 geriatric
      patients retrospectively to assess the safety of geriatric anesthesia.
      Preoperatively, the percentages of cases with cardiovascular and pulmonary
      abnormalities were 49.6% (276 cases) and 21.8% (121 cases) respectively. 77
      percent of out patients (428 cases) were in the ASA class II physical status. The
      most common intraoperative complication was blood pressure instability and the
      incidence was noted to be of 34.8% (130 cases) with general anesthesia and of
      15.8% (26 cases) with regional anesthesia. With general anesthesia, incidence for
      postoperative events such as non-fatal complications (i.e., sore throat and eye
      dryness), cardiovascular abnormalities and pulmonary disorders were found to be
      39.0% (146 cases), 22.2% (83 cases) and 6.2% (23 cases) respectively. With
      regional anesthesia, the most common postoperative event was blood pressure
      instability (incidence: 21.2%, 35 cases). Total mortality rate of the first 15
      postoperative days was 2.0% (11 cases). Mortality rate in elective and emergency
      surgery was 1.1% (5 cases) and 6.8% (6 cases) respectively. Causes of death were
      mainly related to illness deterioration (cancer and infection) or location of
      surgery. Death due to anesthetic mishap was nil in this study. IN CONCLUSION:
      Most geriatric patients had more than one system or one organ dysfunction before
      operation. Cardiovascular instability was the most common intraoperative
      complication. Postoperative mortality correlates closely with the preoperative
      ASA physical status. Mortality rate was significantly higher in emergency cases
      than in elective cases. A thorough pre-operative assessment and proper
      perioperative management are mandatory in geriatric anesthesia.

PMID- 1344236
TI  - [Intramuscular meperidine for the prevention of shivering in spinal anesthesia].
AB  - Intravenous meperidine 25mg has been employed effectively to treat shivering
      following regional anesthesia and general anesthesia. The study was designed to
      evaluate the effectiveness of intramuscular meperidine for the prevention of
      shivering in spinal anesthesia. The series consisted of 60 patients who were
      divided into 2 groups with 30 patients in each, undergoing lower abdominal or
      lower extremity surgery. All patients were given diazepam 0.1mg/kg i.v. for
      anxiolysis when they came to the operating room. In a double blind and randomized
      fashion, patients in the study (meperidine) group received meperidine 25mg IM (=
      0.5ml). In the control group 0.9% N/S 0.5ml IM was given instead. All patients
      received spinal anesthesia 15 minutes later. Measurement of the levels of sensory
      loss to pinprick was made. The ambient temperature and the rectal temperature
      were continuously monitored to evaluate the effect of the change in body
      temperature on shivering during operation. The degree and the occurrence of
      shivering were carefully evaluated and recorded by a blind-trust observer. There
      was no significant difference in maximal analgesic level, ambient temperature and
      change of rectal temperature during operation between the groups. Shivering
      occurred in 17 patients (56.7%) in the saline group with an onset time of 7.9 +/-
      2.5min following spinal anesthesia. In the meperidine group, shivering occurred
      only in 3 patients (10%) with an onset time of 54 +/- 29.5min after spinal
      anesthesia. There was a significantly lower incidence of shivering in the
      meperidine group than in the saline group (p < 0.005).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1344237
TI  - Neonatal status in cesarean section under epidural anesthesia with supplementary
      oxygen.
AB  - Simple O2 mask has been used in patient under regional anesthesia for increasing
      the FiO2, especially in the aged and the pregnant. The relationships between
      maternal FiO2 and umbilical arterial (UA) and venous (UV) PO2, PCO2, pH, and
      neonatal Apgar score were studied in 45 patients receiving Cesarean section under
      epidural anesthesia. 2% xylocaine 18-20 ml with adrenaline 1:200,000 was used to
      attain the sensory level of T-4. Patients were allocated randomly into three
      groups. Group I, acting as a control group, breath only room air during the
      course of anesthesia. Group II was breathing through a simple face mask with an
      oxygen inflow of 6L/min. Group III was breathing oxygen with a flow rate of
      10L/min through a simple face mask. UA and UV blood samples were collected
      separately at the time of delivery for blood gas analysis. The 1-min, and 5-min
      Apgar scores were recorded also. Mean values of the UA blood samples for the 3
      groups (Gp. I, Gp. II and Gp. III respectively) were: PO2--16.50 mmHg, 20.20 mmHg
      and 19.50 mmHg; PCO2--49.20 mmHg, 48.10 mmHg and 50.3 mmHg; pH--7.31, 7.30 and
      7.30. Mean values of the UV blood samples for the 3 groups (Gp. I, Gp. II and Gp.
      III respectively) were: PO2--28.6 mmHg, 36.9 mmHg and 36.5 mmHg; PCO2--38.20
      mmHg, 38.80 mmHg and 40.40 mmHg; pH--7.36, 7.36 and 7.34. There was a significant
      increase in UA and UV PO2 when using a simple O2 mask (p < 0.001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1344238
TI  - Endotracheal lidocaine instillation in pediatric anesthesia.
AB  - The purpose of this study is to evaluate the effectiveness of lidocaine
      administered via the endotracheal tube in suppressing cough reflex during
      anesthetic recovery in children. Fifty ASA class I-II children, aged from 1-5
      years old undergoing elective abdominal or urogenital surgery were randomly
      assigned into two groups. 2% lidocaine 1.5 mg/kg (1ml = 20mg) was administered in
      group B while normal saline (N/S) 0.1 ml/kg was used in group A (control group).
      Either one of the agents was instilled into the endotracheal tube right before
      the end of operation. Airway responses and other associated phenomena were
      recorded during the recovery period. Recovery condition was categorized into a
      two-grade categories, namely "good", and "poor" to denote the quality of
      recovery. Recovery conditions differ significantly between the control group and
      the experimental group. In group A, 3 patients were classified as the "good"
      grade but 22 patients were categorized in the "poor" grade. Group B (lidocaine
      1.5 mg/kg) has a much better recovery condition than the control group, there
      were 19 in the "good" grade and only 6 in the "poor" grade. The experimental
      group treated with 2% lidocaine presented a significantly better recovery than
      the control group. This effective suppression of the cough reflex might be due to
      the local anesthetic effect exerted by lidocaine. For the sake of safety all
      patients were closely followed up at the post anesthesia room until the return of
      consciousness and laryngeal reflexes. In conclusion, we found that 2% lidocaine
      1.5 mg/kg given intratracheally via the endotracheal tube could attenuate cough
      response during recovery in pediatric anesthesia.

PMID- 1344239
TI  - [Emergency translaryngeal ventilation].
AB  - Every anesthesia providers is aware of the serious consequences of anoxia
      subsequent to acute airway obstruction, and is trained to manage such situations
      when they occur. Nonetheless, a patent airway is not always attainable.
      Percutaneous needle laryngostomy with translaryngeal ventilation has been widely
      advocated for emergency ventilation in desperate situations in which other
      efforts, including intubation have failed. A review of literature suggested that
      using a large bore (> 18 Ga) needle/catheter with a jet ventilator, or
      alternatively connecting it to an oxygen source of high pressure (40-50 psi; i.e.
      anesthesia machine, wall outlet etc.) via a low compliance tubing will
      effectively resuscitate an animal or patient. However, this method may expose the
      patients to the risk of barotrauma which has inhibited its widespread adoption.
      In order to assess this risk, we have conducted an in vitro study employing a
      simple lung simulator and an anesthesia machine. Variables of the experiment
      included the make of the anesthesia machine, size of the needle/catheter, degree
      and duration of depression of the flush valve, as well as the size of the pop-off
      valve opening. Based on the data obtained from our study as well as others by an
      extensive literature review, we have proposed some guidelines for this technique
      when a jet ventilator is not available.

PMID- 1344240
TI  - [The efficacy of intravenous fentanyl patient-controlled analgesia for
      postoperative pain relief].
AB  - The safety and efficacy of patient-controlled analgesia used for postoperative
      pain relief were evaluated. Cumulative 24-hour requirements were analyzed for
      possible correlation with patient characteristics. All patients who used a
      patient-controlled analgesia device for postoperative pain relief were reviewed
      from June to October 1991. The device Baxter's basal/bolus infusor with patient
      control module, was used to deliver fentanyl in 379 patients. The fentanyl
      requirement, verbal analog pain score, first passage of flatus, side effects,
      sedative score, and degree of satisfaction were examined. The fentanyl
      requirement during the first 24 hours after operation was analyzed with regard to
      age, body weight, and sex. The daily fentanyl consumption in the first three
      postoperative days was 928 +/- 352 micrograms (n = 338), 553 +/- 259 micrograms
      (n = 220), and 490 +/- 222 micrograms (n = 71), respectively. The requirement for
      fentanyl during the first 24 hours after surgery was significantly higher than
      for the next two days (p-value < 0.001). Fentanyl consumption correlated well
      with body weight, and inversely with age. No difference was found between
      fentanyl consumption and sex (p-value = 0.4687). The mean time to the first
      passage of flatus in patients with abdominal surgery was 54.6 +/- 26.4 hours. The
      incidence of nausea, vomiting, and dizziness was similar, about 20% of patients.
      Itching was noted in 7% of patients. Oversedation (class 4) was found in three
      patients during the first operative day, the sedative score for other patients
      were around class 1-3. No patient exhibited signs of respiratory depression or
      withdrawal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1344241
TI  - Anesthetic management of children with upper respiratory tract infection.

PMID- 1344242
TI  - Successful survival from massive air embolism and circulatory arrest during
      cardio-pulmonary bypass.

PMID- 1344243
TI  - Intrapulmonary misplacement of nasogastric tube during anesthesia.

PMID- 1344244
TI  - Sudden cardiac arrest during left thoracoscopic T2 sympathectomy.

PMID- 1344245
TI  - Computer networking as a tool for public health surveillance: the French
      experiment.

PMID- 1344246
TI  - Disease surveillance in China.
AB  - In the past 10 years in China, because social conditions have been stable and the
      public health infrastructure has been well developed, the disease surveillance
      network has substantially improved. A computerized reporting system for
      notifiable diseases has been established that links China's 30 provinces,
      autonomous regions, and municipalities. Mechanisms for providing timely feedback
      to units that report data and for systematically assessing the quality of those
      data are important attributes of this system. During this period, data from the
      surveillance system have become more representative, and, simultaneously, more
      effective use of data has been promoted. Data collected through the disease
      surveillance network serve as the basis for formulating health policies and
      devising strategies for preventing disease.

PMID- 1344247
TI  - Using surveillance data to set health objectives: experiences from the national
      epidemiology board of Thailand.

PMID- 1344248
TI  - Surveillance data for policy: a national and state approach.

PMID- 1344249
TI  - Communicating information for action.

PMID- 1344250
TI  - Conveying public health surveillance data effectively.

PMID- 1344251
TI  - Surveillance: present and future.

PMID- 1344252
TI  - Communicating with decision makers: experiences from Zimbabwe.

PMID- 1344253
TI  - Epidemiologic surveillance of the tobacco epidemic.

PMID- 1344254
TI  - Surveillance for environmental diseases in Hungary.

PMID- 1344255
TI  - Monitoring trends and determinants in cardiovascular disease in Germany: results
      of the MONICA Project Augsburg, 1985-1990.

PMID- 1344256
TI  - The role of surveillance in reducing morbidity and mortality from injuries.

PMID- 1344257
TI  - Surveillance: the tool and its users.

PMID- 1344258
TI  - Future directions for surveillance.

PMID- 1344259
TI  - Public health surveillance on the world health agenda.

PMID- 1344261
TI  - Local-area monitoring and supervision in Indonesia: tools to improve the coverage
      and quality of vaccination services.

PMID- 1344260
TI  - The role of public health surveillance: information for effective action in
      public health.
AB  - Public health surveillance can provide the quantitative information needed for
      setting priorities and establishing rational health policy. Although there are
      many examples of the effective use of such information, the full potential for
      surveillance has not yet been realized. To a large degree, failure to achieve
      this potential has resulted from limited perspectives regarding the role and
      conduct of surveillance. Both practitioners (those who conduct surveillance) and
      users (those who apply surveillance data in a real-world setting) have fallen
      victim to such myopia. Public health surveillance must be advocated as an
      essential part of the global health agenda if we are to achieve international
      goals for improving health status. As we improve our appreciation of the variety
      of uses for public health surveillance data, we need to understand more fully the
      determinants of the decision-making process. Effective dissemination of
      information and effective communication are as important as data collection and
      analysis. No longer do we have--or should we have--the luxury of collecting
      information for its own sake. The information collected must have a demonstrated
      utility. Developing and training personnel to have expertise in public health
      surveillance will necessarily incur opportunity costs. Bridging gaps in data
      methodology and coverage will force us to weigh alternatives and to compromise.
      We hope that the International Symposium on Public Health Surveillance will
      accomplish several goals. First, we wish to foster international understanding of
      the definition, role, and importance of surveillance in reducing morbidity and
      mortality, in improving quality of life, and in setting effective health
      priorities. Second, we hope that this symposium will serve as a springboard for
      identifying issues and topics that can be addressed in greater depth at future
      international meetings. Finally, we see the symposium as an essential step in
      developing a firm commitment on the part of countries, donor agencies, and
      multilateral organizations to develop the essential capacity for public health
      surveillance throughout the world. Each country should have the capacity to
      measure and monitor changes in health status, risk factors, and health-service
      access and utilization among its people. All countries should have the means to
      detect emerging health problems and implement measures for their control, to
      evaluate the impact of health policies and programs, and to communicate health
      information in a meaningful fashion to policymakers and the public. If we are
      successful in these endeavors, the long-term effects on the public's health will
      be well worth the struggle required to achieve them.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1344262
TI  - Moving public health surveillance onto the health agenda: the perspective of a
      district health officer.

PMID- 1344263
TI  - Perspectives of the legislator: allocating resources.

PMID- 1344264
TI  - The World Bank's health sector priorities review: implications for surveillance
      data.

PMID- 1344265
TI  - Public health surveillance: where are we? Where are we going?

PMID- 1344266
TI  - Using surveillance data for decision making in public health.

PMID- 1344268
TI  - Setting priorities: the Canadian experience in communicable disease surveillance.

PMID- 1344267
TI  - Key issues in public health surveillance for the 1990s.
AB  - In this paper, we have proposed a wider scope for public health surveillance in
      order to incorporate demographic and health-system monitoring, along with
      activities conventionally associated with epidemiologic surveillance. This new
      conception stems, in turn, from a revised definition of public health, which
      describes, not a sector of activity or a type of health service, but a level of
      aggregation based on the population at large. In our review of the ideas that
      lead to the institutionalization of health surveillance, we have stressed the
      broad concepts developed by such pioneers as Graunt and Petty. Their original
      concepts emerged from their active concerns for the public's health at a time
      when no scientific theory of contagion was available, let alone any knowledge
      about how to treat persons for the major diseases. Later on, largely as the
      result of impressive advances in biomedical knowledge, public health surveillance
      tended to specialize and to concentrate predominantly on disease outbreaks and on
      salient adverse health conditions. Health surveillance became closely associated
      with epidemiologic surveillance, which in turn became associated with the ability
      to respond promptly to adverse health outcomes. Recently, we have witnessed a
      gradual broadening of both the concepts and the practice of health surveillance.
      Paradoxically, the new currents tend to recapture some of the spirit and scope of
      the early definitions, prompted perhaps by grave historical parallels--we face
      newly emerging health problems for which we have no clear-cut solutions. If one
      element needs to be stressed to promote the objectives of health surveillance
      today, it is that we need the ability to anticipate health outcomes and not just
      respond to them. This, in turn, requires that we give more weight to the
      surveillance of risk factors and that we increase our understanding of the
      complex causal interrelationships that link exposure to risk factors--including
      behavioral, life-style, and environmental ones--with adverse health conditions
      and disability. Needless to say, the first and foremost aim of health care--and
      modern surveillance is one of the tools needed to achieve this aim--is to promote
      the well-being of individuals while improving their health.

PMID- 1344269
TI  - Priorities for public health surveillance when resources are limited.

PMID- 1344270
TI  - Informatics in public health surveillance: current issues and future
      perspectives.

PMID- 1344272
TI  - The role and responsibilities of oral health personnel in the control and
      prevention of HIV infection/AIDS in Africa.

PMID- 1344271
TI  - AIDS and infection control: experiences, attitudes, knowledge and perception of
      occupational hazards among Nigerian dentists.
AB  - A questionnaire survey of 79 Nigerian dentists aged 21-60 years was carried out
      to evaluate their experiences, attitudes, knowledge, and infection control
      practices in relation to HIV infection. Their perceptions of various occupational
      hazards were also probed. 84.4% of them held the view that HIV-infected/AIDS
      patients should be treated in special treatment clinics. The risk of becoming
      infected was the paramount fear expressed by 88.6% of the dentists. This fear can
      be explained by the inadequate facilities in various dental clinics reported by
      79.7% of them. Despite their lack of clinical experience in the management of
      oral manifestations of AIDS, a large proportion of them were quite knowledgeable.
      However, HIV infection was perceived with the highest degree of concern as the
      greatest occupational hazard by 87.2% of the dentists. Interdisciplinary
      collaboration among health professionals should be intensified to enhance prompt
      referral and comprehensive treatment of AIDS patients.

PMID- 1344273
TI  - Variations in occlusal and space characteristics in a series of 6-18-year olds,
      in Ilala District, Tanzania.
AB  - This study was carried out in Ilala District, Tanzania as part of a major oral
      health survey. The aim of the study was to investigate the variation in different
      occlusal and space characteristics among children and adolescents in different
      age group. A total of 698 children and adolescents aged 6-18 years were examined
      clinically. The subjects were categorized into three age groups, 6-9 years with
      early mixed dentition, 10-14 years with late mixed dentition and 15-18 years with
      permanent dentition. The examiners were calibrated before the survey and the
      agreement was satisfactory. Anteroposterior relationships of the dental arches
      were measured according to Angle's classification. Other occlusal and space
      variables included overjet, overbite, openbite, crossbite, crowding, spacing, and
      separate determination of diastema mediale. Most of the subjects in different age
      groups, 93-96%, had Angle's Class I molar occlusion. Large overjet (> 5 mm)
      occurred in 3-5% of the subjects. Deep bite (> 5 mm) was observed in about 2% of
      the children in all age groups. Anterior open bite was the most prevalent
      occlusal anomaly in all age groups, noted in 9-13% of the subjects. Transversal
      occlusal anomalies were rare. More than 33% of the subjects had spacing while
      less than 10% had crowding of the dentition. These results indicate that using
      the present criteria, most 6- to 18-year olds in Ilala district have optimal
      sagittal occlusion and a lot of spacing. The most common occlusal anomaly was
      anterior openbite.

PMID- 1344274
TI  - A preliminary study of the periodontal status and treatment needs of elderly
      Nigerian subjects.
AB  - One hundred elderly subjects comprising of residents of old peoples homes and
      patients attending routine outpatients clinic at the Lagos University Teaching
      Hospital were examined in Lagos. The mean age of subjects was 68.7 years. Using
      the Community Periodontal Index of Treatment Needs (CPITN) it was found that 23%
      had tooth deposits (plaque/calculusonly) whilst 70% had shallow or deep pockets.
      87% of these elderly subjects were caries-free and none had restored or filled
      teeth. However, more than half of the subjects had an average missing teeth
      number of 8.829% of the subjects needed extraction with an average of 3.3 teeth.
      Among the subjects that needed dental extraction, none had healthy periodontal
      condition whereas, 79% of them were caries free. It is concluded from this study
      that the periodontal status of the subjects was poor and the incidence of caries
      was low. Furthermore, the majority of the missing teeth could have been largely
      due to periodontal disease. Dental health education which is directed towards
      improved oral hygiene procedures is suggested for the elderly dental population.
      It is also suggested that elderly patients be given free or subsidised treatment.
      Furthermore, the National Health Policy should be directed towards domiciliary
      dental treatment for the compromised elderly patients.

PMID- 1344275
TI  - A retrospective study of characteristics of impacted mandibular wisdom teeth in
      110 patients treated in Nairobi, Kenya.
AB  - Analysis of 110 records of patients who presented with impacted mandibular 3rd
      molars was carried out to determine the frequency of occurrence of unilateral and
      bilateral impactions and their characteristics. 68.2% of the patients had
      bilateral impactions. Among the patients with bilateral impactions, 72% had
      mesioangular impaction occurring either bilaterally or in combination with other
      types of impaction. Furthermore, 38.7% mesioangular impactions were observed on
      the right and left sides in the patients with bilateral impactions. Among the
      patients with unilateral impactions 40.2% presented with mesioangular impaction,
      while 25.7% presented with distoangular impactions. While these observations
      support the general consensus regarding aetiology of mandibular 3rd molar
      impactions as being tooth-tissue discrepancy, the possible influence of other
      factors is suggested.

PMID- 1344276
TI  - Case report of dentigerous cyst of lower incisor.
AB  - This paper reviews the pathogenesis, clinical features and the behaviour of
      dentigerous cyst. A case of mandibular dentigerous cyst involving the incisor
      tooth (an unusual site) is presented to illustrate this pattern of behaviour. A
      recurrent pyogenic granuloma in the region of the lower incisors prevented the
      eruption of the lower left incisor with subsequent cystic formation around the
      tooth. The histological and radiological presentation is consistent with that of
      a dentigerous cyst. The significance of the potential of the cyst lining is
      stressed. The cyst was enucleated with the associated tooth as the latter was not
      in a favourable position to erupt. There was no recurrence after one year of
      treatment.

PMID- 1344277
TI  - Oral health promotion and health education programmes for Nigeria--policy
      guidelines.
AB  - Nigeria like other developing countries is presently faced with the arduous
      problem of coping with scarce resources to control existing and increasing oral
      disease levels. The World Health Organization has emphasized the importance of
      oral health promotion for initiating successful, effective, preventive oral
      health programmes. At present however, Nigeria is without formal oral health
      promotion and health education policies or programmes. In the "National Policy
      and Strategy to Achieve Health for All Nigerians" (Federal Ministry of Health
      1986), no specific mention was made of oral health promotion or oral health
      education. The present paper therefore proposes definitive policy guidelines that
      will help in the development of coherent oral health promotion programmes for the
      country. The approach proposed tackles causes common to a number of chronic
      diseases and incorporates oral health into general health strategies.

PMID- 1344278
TI  - Organic tooth wear--overlooked in anatomy texts.

PMID- 1344279
TI  - Clinico-radiological profile and management of ameloblastoma.

PMID- 1344280
TI  - Iso-eugenol and zinc oxide as a liner and a filler in restorative dentistry.

PMID- 1344281
TI  - Evaluation of indigenous casting alloy for fixed restorations in dentistry.

PMID- 1344282
TI  - Magnets in orthodontics.

PMID- 1344283
TI  - Anodontia associated with hypohidrotic ectodermal dysplasia.

PMID- 1344284
TI  - The periotest--a periodontal diagnostic aid.

PMID- 1344285
TI  - Faciomaxillary fractures in Libya--retrospective analysis of 14 years.

PMID- 1344286
TI  - Racial comparison of dento-skeleto-facial patterns of adults from Kerala with
      Caucasians, Chinese, Japanese and Negroes.

PMID- 1344287
TI  - Catecholamine excretion in children waiting for treatment: a simple test for the
      objective evaluation of anxiety.

PMID- 1344288
TI  - Dystrophin cytochemistry in mdx mouse muscles injected with labeled normal
      myoblasts.
AB  - A new technique enables correlation of dystrophin expression with the location of
      donor versus host nuclei in the same sections of mdx mouse muscle injected with
      normal myoblasts. Myoblasts from C57BL/6J mice or from humans were labeled with
      0.01% fluoro-gold (FG) in Dulbecco's Modified Eagles Medium (DMEM) for 16 h at 37
      degrees C before myoblast transfer. About 3 x 10(4) myoblasts were injected into
      the quadriceps muscles of mdx mice immunosuppressed with cyclosporine A (CsA). At
      11, 21, or 25 days after myoblast transfer, injected muscles were dissected out
      and sectioned. These mouse sections were processed for dystrophin and then
      labeled with a fluorescent nucleus counterstain, 5 micrograms% Hoechst 33342 in
      phosphate-buffered saline (PBS), for 10 min at room temperature. Fluoro-gold
      labeling corresponding with Hoechst 33342 staining indicated survival of normal
      nuclei in dystrophic muscle. Dystrophin was found in the sarcolemma of myofibers
      containing FG-labeled nuclei but not of myofibers containing only Hoechst 33342
      labeled nuclei. Control muscle samples showed neither FG labeling nor dystrophin.
      This study demonstrates that the donor human and mouse myoblasts survived and
      developed in host mouse muscles for at least 25 days after myoblast transfer, and
      that the localization of their normal nuclei correlates with dystrophin
      expression in muscle fibers of immunosuppressed mdx host mice.

PMID- 1344289
TI  - Osteogenesis in marrow-derived mesenchymal cell porous ceramic composites
      transplanted subcutaneously: effect of fibronectin and laminin on cell retention
      and rate of osteogenic expression.
AB  - Cultured-expanded rat marrow-derived mesenchymal cells differentiate into
      osteoblasts when combined with a porous calcium phosphate delivery vehicle and
      subsequently implanted in vivo. In this study, the effects of ceramic
      pretreatment with the cell-binding proteins fibronectin and laminin on the
      osteogenic expression of marrow-derived mesenchymal cells were assessed by
      scanning electron microscopy, [3H]-thymidine-labeled cell quantitation, and
      histological evaluation of bone formation. Scanning electron microscopic
      observations showed that marrow-derived mesenchymal cells rapidly spread and
      attach to both fibronectin- or laminin-adsorbed ceramic surfaces but retain a
      rounded morphology on untreated ceramic surfaces. Quantitation of [3H]-thymidine
      labeled cells demonstrated that laminin and fibronectin preadsorbed ceramics
      retain approximately double the number of marrow-derived mesenchymal cells than
      do untreated ceramics harvested 1 wk postimplantation. Histological observations
      indicate that the amount of time required to first detect osteogenesis was
      shortened significantly by pretreatment of the ceramic with either fibronectin or
      laminin. Fibronectin- and laminin-coated ceramic composite samples were observed
      to contain bone within 2 wk postimplantation, while in untreated ceramic the
      earliest observation of bone was at 4 wk postimplantation. A comparison was made
      of the initial cell-loading, in vivo cell retention characteristics, and rate of
      osteogenesis initiation of marrow-derived mesenchymal cells on two types of
      ceramic with different pore structure and chemical composition, with and without
      preadsorption with fibronectin or laminin. "Biphasic" ceramics contain randomly
      distributed pores 200-400 microns in diameter, and "coral-based" ceramics have
      continuous pores of approximately 200 microns in diameter. Laminin or fibronectin
      preadsorption significantly increases the number of cells retained in all ceramic
      test groups by day 7 postimplantation. In addition, by day 7 postimplantation,
      the biphasic ceramics retain a significantly greater number of cells for all test
      groups than do coral-based ceramics. The biphasic ceramics consistently have more
      specimens positive for bone with the identical cell-loading conditions used
      throughout this study. These results indicate that the retention of cells within
      the ceramic is an important factor for optimization of marrow mesenchymal cell
      initiated bone formation. The retention of cells within ceramics is augmented by
      the adsorption of the cell-binding proteins laminin and fibronectin, but this
      effect varies depending on ceramic pore structure and/or chemical composition.

PMID- 1344290
TI  - Human cortical neuronal cell line (HCN-1): further in vitro characterization and
      suitability for brain transplantation.
AB  - The human neuronal cell-1 (HCN-1) line has recently been established. Under
      favorable conditions, these cells differentiate into mature neuronal phenotypes.
      Here we report on further characterization of these cells. Cultured HCN-1 cells
      express fibronectin immunoreactivity and grow well on fibronectin substrate but
      do not respond to human bFGF. In the undifferentiated state, some HCN-1 cells
      show MHC class I antigen expression. After differentiation, HCN-1 cells and their
      processes are MHC class I negative. On the other hand, interferon-gamma
      stimulation enhances MHC class I expression but does not induce MHC class II
      immunoreactivity. Our in vitro data indicate that HCN-1 cells express mixed
      characteristics, including both neuronal and mesenchymal markers, and are
      consistent with the suggestion that the HCN-1 cell line resembles an immature
      neuroepithelial cell precursor with a complex origin. One possible application of
      the use of the HCN-1 cells includes intracerebral transplantation. We also
      examined the survival of dissociated HCN-1 cells implanted into rat brain
      parenchyma. The host animals were not immunosuppressed. Despite expression of MHC
      class I antigens, small clusters of HCN-1 cells survived in the rat brain. These
      xenografts did not induce distinct immunological responses within the host brain
      tissue. Surviving HCN-1 cells demonstrated similar features to those observed in
      culture. Our preliminary results suggest that the HCN-1 cell line would be
      suitable for intracerebral transplantation in primates or humans. However, it may
      be that short-term host immunosuppression or addition of HCN-1 cell
      differentiation factors would be beneficial for enhanced cell survival.

PMID- 1344291
TI  - Entrapment of cultured pancreas islets in three-dimensional collagen matrices.
AB  - In vitro culture of islets of Langerhans decreases their immunogenicity,
      presumably by eliminating passenger leukocytes and other Ia+ presenting cells
      within the islets. Islets cultivated in petri dishes either at 37 degrees C or at
      25 degrees C gradually disintegrate during culture in a time-dependent manner
      which is related to the free-floating condition of the islets. Also, a fraction
      of the islets disperse as single cells and beta-cell aggregates or adhere to the
      bottom of the culture dishes. Thus, the retrieval rate of transplantable islets
      is dampened due to their disintegration and spontaneous dispersion in
      conventional petri dish cultures. Entrapment of freshly harvested islets of
      Langerhans in a three-dimensional collagen matrix was studied as an alternative
      method for islet cultivation. The contraction of collagen fibrils during in vitro
      culture counteracts the dispersion of islets and helps in maintaining their
      integrity while in culture. It was observed that the entrapped islets maintain
      satisfactory morphology, viability, and capability of glucose-dependent insulin
      secretion for over 2 wk. The oxygen consumption rate and glucose metabolism of
      these islets was not deranged when entrapped in collagen. Also, the retrieval of
      islets is easier and more efficient than that observed in conventional culture
      systems. Our results indicate that culture of islets in three-dimensional
      collagen gels can potentially develop into an ideal system applicable to clinical
      transplantation of cultured islets or beta-cell aggregates.

PMID- 1344292
TI  - Influence of different substrates in detoxification activity of adult rat
      hepatocytes in long-term culture: implications for transplantation.
AB  - Substrates used to immobilize hepatocytes for transplantation govern attachment
      and long-term metabolic activity of these cells. The choice of these substrates
      is based on the familiarity with proteinaceous materials that are constituents of
      the extracellular matrix. The use of substrates that recognize carbohydrates on
      the cell surface may provide an alternative method to attach adult mammalian
      hepatocytes. In this study, immobilized lectins on tissue culture plasticware
      were used to support hepatocyte attachment. Long-term cultures with these
      substrates were compared with control cultures seeded on a mixture of collagen
      types I and III (Vitrogen). To evaluate the attachment efficiency and long-term
      maintenance of diazepam metabolic activity of hepatocytes seeded on different
      commercially available plasticware, four different types of polymers (supplied as
      60-mm dishes) were tested. Diazepam, a benzodiazepine metabolized by the P450
      intracytoplasmic pathway, is associated with a synaptic receptor (GABA
      benzodiazepine receptor) which plays an important role in hepatic coma.
      Polymethylpentene, a derivative of polypropylene treated by plasma discharge, was
      the best polymer to maintain P450 phenotypic expression, although other polymers
      provided similar cell attachment efficiencies. The amounts of adsorbed
      concanavalin A, Arachis hypogaea (peanut), Lens culinaris, and Pisum sativum
      agglutinin correlate with the percentage values of hepatocyte attachment. Cell
      attachment to wheat germ agglutinin increased with increased lectin
      concentrations in spite of constant amounts of adsorbed lectin, whereas
      hepatocyte attachment to Bandieraea simplicifolia agglutinin was lower and did
      not change at different lectin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1344293
TI  - Comparison of fetal rabbit brain xenografts to three different strains of athymic
      nude rats: electrophysiological and immunohistochemical studies of intraocular
      grafts.
AB  - Interest in the use of neural tissue transplantation for the study of CNS
      development and maturation and the potential use of this technique for the
      treatment of certain degenerative CNS disorders has led to our use of
      transplantation of neural tissue across species lines. Prior to extensive
      transplantation studies using athymic rats as recipients, we wished to evaluate
      the currently available strains of athymic rat for their suitability as host
      animals for xenografts of neural tissue. Fetal cerebellar and cerebral cortex
      tissue from rabbit brain of gestational age 20-25 days was dissected and
      transplanted to the anterior chamber of the eye of Harlan Wisconsin, Fisher 344
      Jnu, or NCI-Harlan athymic nude rat strains. The brain tissue grafts were allowed
      to mature for 3 mo during which time the size and vascularity of each graft was
      monitored through the cornea of anesthetized hosts. In each group all of the
      transplants survived and grew to varying extents in the anterior chamber of the
      eye. Following the growth study in vivo extracellular recording of single
      neuronal activity was performed. Spontaneous neural activity was found in most
      transplants in all three groups with no difference in the viability or discharge
      rates of neurons between the groups. Illumination of the ipsilateral eye
      increased the firing rate of neurons in all three groups, suggesting excitatory
      cholinergic innervation of the grafted neurons from the host parasympathetic iris
      ground plexus. Antibodies directed against neurofilament protein, glial
      fibrillary acidic protein, synapsin, and tyrosine hydroxylase were used to
      characterize the transplants immunocytochemically and revealed no differences
      between the grafts in the three groups of recipients. All transplants contained
      significant numbers of glial and neuronal elements with the distribution
      resembling that in adult brain tissue. Some of the transplants contained a sparse
      innervation of tyrosine hydroxylase-positive fibers from the sympathetic plexus
      of the host iris. Furthermore, synapsin-immunoreactivity suggested that
      synaptogenesis had taken place within the grafts. Histological examination of the
      grafts revealed that 67% of the grafts had been infiltrated, to varying extents,
      by lymphocytes which led to areas of cell lysis and necrosis. All host animals
      had populations of T-cell receptor positive cells, most of which also expressed
      the T-cell surface antigens CD4 and CD8. However, no transplants were overtly
      rejected over the 15 wk period of study.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1344294
TI  - Reversal of experimental diabetes by injection of syngeneic islets into
      peripheral veins.
AB  - This study was undertaken to evaluate the safety and effectiveness of intravenous
      (i.v.) injection of islets, via a peripheral vein, in the treatment of
      experimental diabetes in highly inbred Lewis rats. Rats were made diabetic by the
      i.v. injection of streptozocin, and donor islets were isolated from neonatal
      rats. Two wk after the induction of diabetes, rats with glucose concentrations >
      19 mM were divided into two groups: one group of six rats was injected with 2000
      neonatal islets into the external jugular vein; the second group of rats, acting
      as control, was injected in the same vein with medium alone. Within 2 wk of the
      islet transplant, 100% (6/6) of the rats were cured of the diabetes. None of the
      control rats experienced any improvement. As expected, pancreatic islets so
      administered embolized to the lungs. Glucose tolerance tests in the rats
      receiving the islet transplant were indistinguishable from normal rats. These
      results could be important to clinical transplantation if the procedure is as
      successful in larger animals using autotransplanted islets or allografts
      protected from immune rejection.

PMID- 1344295
TI  - Feasibility, safety, and efficacy of myoblast transfer therapy on Duchenne
      muscular dystrophy boys.
AB  - Five billion normal myoblasts were injected into each of 21 Duchenne muscular
      dystrophy (DMD) boys aged 6-14 yr to assess the feasibility, safety, and efficacy
      of the Phase II myoblast transfer therapy (MTT). The Phase II study was designed
      to strengthen muscles of both lower limbs. Forty-eight intramuscular injections
      transferred the myoblasts into 22 major muscles at 55.6 x 10(6)/mL in 10 min
      under general anesthesia. Eleven boys had received 8 million myoblasts each 1 yr
      ago in the Phase I MTT. In the Phase II study, eight of them had their myoblasts
      subcultured from reserves frozen 1 yr ago. The donor myoblasts for each of the
      remaining boys were cultured from satellite cells derived from a 1-g muscle
      biopsy of a normal male who might or might not be histocompatible with the
      recipient. The immunosuppressant cyclosporine (Cy) is being administered to
      recipients for 6 mo after MTT to facilitate donor cell survival. There was no
      evidence of an adverse reaction to MTT or Cy as determined by serial laboratory
      evaluations including electrolytes, creatinine, and urea. Early objective
      functional tests using the KinCom Robotic Dynamometer were conducted on 13
      subjects aged 6 to 13 before MTT and at 3 mo after MTT. Of the 69 muscle groups
      (knee extensors, knee flexors, plantar flexors) tested for isometric force
      generation in these subjects, 43% showed mean increase of 41.3% +/- 5.9 SEM, 38%
      showed no change, and 19% showed continuous force reduction of 23.4% +/- 3.1 SEM.
      The remaining subjects await the 3-mo post-MTT evaluation. The results indicate
      that 1) MTT is safe; 2) MTT increases muscle strength in DMD: 81% of the muscles
      tested showed either increase in strength or did not show continuous loss of
      strength; 3) more than 5 billion myoblasts can be cultured from 1 g normal muscle
      biopsy, providing unprecedented numbers of cells for MTT; 4) myoblasts, frozen
      over 1 yr, retain the ability to proliferate from 10 million to 5 billion, and to
      form normal myofibers; 5) injections of 5 billion myoblasts have not provoked any
      immunological rejection symptoms in the Phase II subjects, 11 of whom received 8
      million myoblasts in the Phase I MTT a year ago; 6) it is safe to perform
      multiple injections of myoblasts into lower limb muscles without formation of
      emboli; and 7) donor cell rejection by the recipient can be prevented with Cy
      when properly managed.

PMID- 1344296
TI  - The effect of transplantation site and islet mass on long-term survival and
      metabolic and hormonal function of canine purified islet autografts.
AB  - Determination of the long-term function of islet transplantation in relation to
      the implantation site and the numbers of islets is of scientific interest and,
      with human islet transplant trials in progress, is a pressing clinical question.
      In this study, highly purified canine islets were isolated by collagenase
      digestion and Ficoll purification, and autotransplanted into either the spleen
      (in 10 dogs) or the liver (in 12 dogs). Dogs transplanted with islets into the
      spleen or liver received 264,300 +/- 20,300 (mean +/- SEM) and 158,600 +/- 15,000
      islet equivalents (150-microns-sized islets) respectively. Graft survival at 1 yr
      was 86% in intrasplenic islet autografts (ISTx) and 50% in intraportal islet
      autografts (IPTx). Intravenous glucose tolerance tests and mixed meal-oral
      glucose tests were performed 1-12 mo from islet transplantation. Compared to
      controls, ISTx and IPTx dogs showed a similar decrease of glucose tolerance after
      both intravenous glucose tolerance tests and mixed meal-oral glucose tests. On
      intravenous glucose tolerance tests, plasma insulin levels were lower in ISTx
      than in IPTx dogs and controls. On mixed meal-oral glucose tests, insulin values
      were higher in IPTx dogs than in controls. There was a positive correlation (r =
      .56, p < 0.05) between the number of transplanted islet equivalents and the K
      values. These results demonstrate that, in dogs with islet transplant: 1) long
      term islet survival can be achieved in the spleen better than in the liver; 2)
      islet survival is related to the mass of transplanted islets in the spleen, but
      not in the liver, where other factors probably affect islet survival; 3) the
      ability of metabolizing glucose is reduced after both intrasplenic and
      intraportal islet autografts; 4) both reduced insulin secretion (predominant in
      ISTx dogs on intravenous glucose tolerance testing) and insulin resistance
      (predominant in IPTx dogs on mixed meal-oral glucose tests) are the probable
      causes of the decreased glucose tolerance.

PMID- 1344297
TI  - Polymer-encapsulated PC12 cells: long-term survival and associated reduction in
      lesion-induced rotational behavior.
AB  - Intrastriatal implantation of a dopaminergic cell line surrounded by a permeable,
      thermoplastic membrane was investigated as a method of long-term dopamine (DA)
      delivery within the central nervous system (CNS). An increase in DA release from
      PC12 cell-loaded capsules maintained in vitro was associated with an increase in
      mitotic activity of the encapsulated cell line. A significant reduction in
      apomorphine-induced rotational behavior was observed after PC12 cell-containing
      capsules were implanted into unilaterally 6-hydroxydopamine (6-OHDA) lesioned
      rats, which was sustained for 24 wk. Four wk after implantation, microdialysis
      studies revealed the presence of DA near PC12 cell-containing capsules, which was
      comparable to extracellular striatal levels of unlesioned controls. Extracellular
      striatal DA was undetectable by microdialysis in lesioned animals near empty
      polymer capsules. Histological analysis after 24 wk in vivo demonstrated that
      encapsulated PC12 cells survived, continued to express tyrosine hydroxylase, and
      that encapsulation prevented tumorigenesis. The data suggested that the release
      of a diffusible substance, most likely DA, from an implant is sufficient to exert
      a long-term functional influence upon 6-OHDA unilaterally lesioned rats and that
      capsules containing DA-secreting cells may be an effective method of long-term DA
      delivery in the CNS.

PMID- 1344298
TI  - A critical reappraisal of gastrointestinal complications of allogeneic bone
      marrow transplantation.
AB  - Gastrointestinal toxicity is a common early complication of allogeneic bone
      marrow transplants. Etiologies include mucosal damage from pretransplant
      conditioning, opportunistic infection, and graft-versus-host disease. Because the
      clinical, laboratory, radiographic, and histological findings of acute graft
      versus-host disease are nonspecific, accurate diagnosis is difficult or
      impossible. We review the differential diagnosis of gastrointestinal
      complications of bone marrow transplants and implications for therapy.

PMID- 1344299
TI  - Peer review for fetal tissue transplantation research.

PMID- 1344300
TI  - Repeated transplantation of microencapsulated hepatocytes for sustained
      correction of hyperbilirubinemia in Gunn rats.
AB  - In previous studies we demonstrated that transplantation of microencapsulated
      hepatocytes could correct congenital hyperbilirubinemia in Gunn rats for 4 to 6
      wks. Reduction in hyperbilirubinemia followed a single transplantation of
      isolated encapsulated hepatocytes (IEH). After 4 to 6 wks of transplantation IEH
      gradually lose their functionality. To sustain long-term supplementation of liver
      function we have investigated the efficacy of monthly IEH transplantation for 6
      mo. Hepatocytes, isolated from young Wistar rats, were microencapsulated with a
      collagen matrix within an alginate-poly L-lysine composite membrane. We
      transplanted IEH intraperitoneally into homozygous Gunn rats at monthly (4-wk)
      intervals for 6 mo. Control Gunn rats received intraperitoneal transplantations
      of empty microcapsules. Total serum bilirubin was measured in the IEH
      transplanted and control Gunn rats at weekly intervals for the duration of the 6
      month study. A significant (p < 0.01) and sustained decrease (by nearly 50%) in
      total serum bilirubin levels was observed following monthly IEH transplantations
      in Gunn rats for the duration of the study. No such decrease in total serum
      bilirubin levels was seen in the controls. The Gunn rats exhibited good tolerance
      for the multiple IEH transplantations. Thus, repeated IEH transplantation may be
      one strategy for providing long-term supplementation of liver function in
      congenital metabolic liver disease.

PMID- 1344301
TI  - Long-term functional recovery of hepatocytes after cryopreservation in a three
      dimensional culture configuration.
AB  - Hepatocyte cryopreservation is essential to ensure a ready supply of cells for
      use in transplantation or as part of an extracorporeal liver assist device to
      provide on-demand liver support. To date, most of the work on hepatocyte
      cryopreservation has been performed on isolated hepatocytes, and has generally
      yielded cells which display low viability and greatly reduced short-term
      function. This report presents the development of a freezing procedure for
      hepatocytes cultured in a sandwich configuration. A specially designed freezing
      unit was used to provide controlled temperatures throughout the freeze-thaw
      cycle. Cooling rate, warming rate, and final freezing temperature were evaluated
      as to their effect on hepatocyte function as judged by albumin secretion. Under
      optimized conditions (cooling at 5 degrees C/min and warm at > or = 400 degrees
      C/min), freezing to -40 degrees C resulted in full recovery of albumin secretion
      within 2-3 days post-freezing, whereafter albumin secretion levels remained
      normal for the duration of the experiments (2 wks). Freezing to -80 degrees C
      lead to an approximate 70% recovery of long-term protein secretion when compared
      to control cultures. In addition, the overall hepatocyte morphology as judged by
      light microscopy, closely followed the functional results. The sandwich culture
      configuration, thus, enables hepatocytes to maintain a satisfactory level of long
      term protein secretion after a freeze-thaw cycle under optimized conditions, and
      offers an attractive tool for further studies into the mechanisms of freezing
      injury and subsequent hepatocellular recovery. These results are a promising step
      in the development of satisfactory storage procedures for hepatocytes.

PMID- 1344302
TI  - Factors affecting in vitro growth of harvested enterocytes.
AB  - Selective enterocyte transplantation may be an alternative to whole organ
      transplantation for increasing absorptive capacity. Our aim was to determine the
      effect of initial cell number and viability, proportion of intact crypts, and
      basement membrane components (BMC) on the in vitro growth of rabbit enterocytes.
      Enterocytes were harvested using warm trypsinization from ileal segments in 40
      rabbits. Initial cell viability was 92 +/- 4% (mean +/- SD), cell yield was 7.7
      +/- 3.6 x 10(6) cells/cm, and there were 0.51 +/- 0.33 crypts/100 cells. Initial
      cell viability correlated with cell yield (r = -0.508, p < 0.001) and % crypts (r
      = 0.313, p < 0.05). Cell yield also correlated with % crypts (r = -0.645, p <
      0.001). Enterocytes (5 x 10(6)) were incubated in growth media in plain or BMC
      coated growth culture vessels for 14 days. There was a correlation between both
      number of cells seeded (r = 0.824, p < 0.001) and cell viability (r = -0.696, p <
      0.01) and % growth colonies containing epithelial cells at 14 days. Both total
      growth colonies (r = -0.565, p < 0.05) and colonies with epithelial cells (r = 
      0.589, p < 0.05) had a negative correlation with % crypts. Incubating cells in
      BMC coated vessels (n = 6) resulted in significantly more dispase liberated cells
      after 14 days than in plain vessels (n = 6) (6.6 +/- 1.1 vs. 3.8 +/- 1.0 x 10(6),
      p < 0.05) but viability was similar (97 +/- 2% vs. 96 +/- 2%).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1344303
TI  - A 9L gliosarcoma transplantation model for studying adoptive immunotherapy into
      the brains of conscious rats.
AB  - A rat model for brain tumor immunotherapy is described that closely mimics the
      type of treatment that could be administered to humans. It involves surgical
      implantation of a permanent cannula in the brain, through which tumor cells and
      various effector cells and/or cytokines can be injected. The advantage of this
      system over more conventional animal surgical procedures is that conscious
      animals can be treated multiple times while avoiding morbidity and mortality
      associated with reoperative procedures. Using this system to study adoptive
      immunotherapy for brain tumors, we provide evidence that the 9L gliosarcoma tumor
      from the Fischer rat strain can be reduced or destroyed in situ following
      adoptive immunotherapy with specifically activated cytotoxic T lymphocytes.

PMID- 1344304
TI  - A primate model of Huntington's disease: functional neural transplantation and CT
      guided stereotactic procedures.
AB  - In this article, we show that 1) computed tomographic (CT)-guided stereotactic
      infusion of an excitotoxin into the striatum of a nonhuman primate provides a
      useful neuropathologic and behavioral model for Huntington's disease. 2) High
      resolution positron emission tomography (PET) can be used to image the decreased
      glucose utilization and the preservation of dopaminergic terminals in the
      lesioned striatum by using 2-fluoro-deoxy-D-glucose (2FDG) and N-(C-11)-methyl-2
      beta-carbomethoxy-3-beta-phenyl tropane (CPT) as tracers. 3) Transplantation of
      cross-species striatal fetal tissue into the lesioned caudate-putamen reduces
      many of the abnormal motor movements and behavioral changes seen in the
      Huntington's disease primate model. 4) Graft rejection results in the return of
      the abnormal signs of the pregrafted state. These results indicate that treatment
      of the neuronal deficit in Huntington's disease can involve intervention at the
      local neuronal circuit level. CT-guided stereotactic implantation of cells that
      might protect or replace this defective circuitry may eventually provide an
      effective treatment for Huntington's disease.

PMID- 1344305
TI  - Assessment of artificial liver support technology.
AB  - Despite more than 30 yr of research and development, an artificial liver has
      still not yet become clinical reality. Although previous attempts using a
      multiplicity of techniques including hemodialysis, hemoperfusion, plasma
      exchange, extracorporeal perfusion, and crosshemodialysis have shown minor
      improvement in patients with acute hepatic failure, limited clinical trials have
      failed to demonstrate any survival benefit. Encouraged by the progress on
      techniques that maintain long-term cultures of hepatocytes, more recent efforts
      have been directed at the use of hepatocytes as the basis of liver support. This
      review takes a critical look at past and present concepts in the development of
      artificial liver supports and both qualitatively and quantitatively evaluates the
      advantages and disadvantages of the available methodology.

PMID- 1344306
TI  - Autotransplants in advanced non-Hodgkin lymphoma: are they effective?
AB  - Recent data suggest that intensive therapy followed by a bone marrow
      autotransplant is effective in advanced intermediate and high-grade non-Hodgkin
      lymphoma (predominantly large-cell lymphoma). Twelve studies of autotransplants
      were analyzed to determine outcome. Results compared to data from 29 chemotherapy
      studies. Complete remission was reported in 53% of autotransplant recipients
      versus 17% of persons receiving chemotherapy. Two-year disease-free survival was
      16 and 2%, respectively. It is uncertain whether these differences indicate
      superiority of autotransplants or reflect selection biases. Also unknown is
      whether similar results might not be obtained with similarly intensive treatment
      without an autotransplant.

PMID- 1344308
TI  - Endothelial cell senescence inhibits unidirectional endothelialization in vitro.
AB  - We investigated the effects of cellular senescence on unidirectional
      endothelialization in vitro, simulating the anastomotic endothelialization of
      vascular prosthesis. The experiments were carried out with three different
      cumulative population-doubling levels (CPDLs) of bovine aortic endothelial cells
      (ECs), which have finite life span. Young ECs with 22 CPDL, middle aged with 46,
      and senescent with 70 at the time of inoculation were used. The effect of aging
      on unidirectional endothelialization, as well as cellular morphology and
      proliferative and migratory potentials of isolated cells, were qualitatively and
      quantitatively analyzed. The unidirectional endothelialization rate was
      determined by our newly designed method to prepare the square monolayer sheet
      with linear margins between cell-adhesion and noncell-adhesion regions. The
      results showed that endothelial cell senescence retarded not only proliferation
      and migration but also unidirectional endothelialization. Time-lapsed
      videomicroscopic study of unidirectional endothelialization process revealed that
      ECs at several rows back from the leading edge represented much slower rate of
      migration than did the ECs at the leading edge. These findings suggest that high
      cellular mobility observed for the ECs at the leading edge may result in
      localized excessive cell replication. Thus, atherosclerotic vessels containing
      senescent or injured ECs may have limited capability of anastomotic
      endothelialization.

PMID- 1344307
TI  - Embedded adrenal cells graft reduced local and early nonspecific inflammatory
      phenomena which follow agarose beads implantation.
AB  - Microencapsulation of adrenal cells is proposed for reducing the nonspecific
      inflammatory reaction observed around polymer implants. This hypothesis was
      tested by comparing both host cellular reaction and the surrounding graft cell
      populations which appeared either when agarose embedded cells or when empty
      agarose beads were implanted. Our results showed that the fibrotic material that
      surrounded the implanted empty agarose microbeads was not as severe and important
      when adrenal cells were present. Similarly, T lymphocyte population surrounding
      the graft was considerably reduced together with the percentage of CD4 and CD8
      positive cell subpopulations. The activation macrophage marker IaD disappeared.
      Our results support the hypothesis that embedded adrenal cells may be a suitable
      solution for reducing early inflammatory events due to microcapsules
      implantation.

PMID- 1344309
TI  - Epidermal wound healing: the clinical implications of a simple mathematical
      model.
AB  - The role of biochemical regulation in the healing of epidermal wounds remains the
      subject of much biological debate. We have previously developed a mathematical
      model which focuses on the role of mitogenic autoregulation in
      reepithelialization (23-25). Here, we discuss some predictions of our model and
      their clinical relevance. We investigate both the effects of adding mitotic
      regulators to healing wounds and the dependence of healing time on wound shape.
      The latter study suggests a possible mechanism for the control of changes in
      wound shape during healing. The predictions we make are amenable to experimental
      verification, and suggest new ideas for experimental research.

PMID- 1344310
TI  - Quantitative analysis of unidirectional 2-D tissue formation of endothelial
      cells.
AB  - We developed a reliable and quantitative method for measuring the dynamic process
      of unidirectional two-dimensional (2-D) tissue formation of endothelial cells
      (ECs) in vitro. The culturing of bovine ECs in an assembled culture chamber
      provided a square monolayered cell sheet with a linear margin when disassembled
      at the confluency. The cell sheet maintained in culture showed a unidirectional
      which was determined from the daily observation of tissue, allowed us to
      determine quantitatively the dynamic process of unidirectional endothelialization
      in vitro. The endothelialized distance and the endothelializing zone on a glass
      slide were found to be nearly 500 microns/day and 750 microns in width,
      respectively. Thus, the method developed here provided information of the 2-D
      tissue formation process. This model would be useful as an in vitro model which
      simulates the anastomotic endothelialization of an artificial vascular graft.

PMID- 1344311
TI  - Cell transplantation for myocardial repair: an experimental approach.
AB  - Myocardium lacks the ability to regenerate following injury. This is in contrast
      to skeletal muscle (SKM), in which capacity for tissue repair is attributed to
      the presence of satellite cells. It was hypothesized that SKM satellite cells
      multiplied in vitro could be used to repair injured heart muscle. Fourteen dogs
      underwent explantation of the anterior tibialis muscle. Satellite cells were
      multiplied in vitro and their nuclei were labeled with tritiated thymidine 24 h
      prior to implantation. The same dogs were then subjected successfully to a
      myocardial injury by the application of a cryoprobe. The cells were suspended in
      serum-free growth medium and autotransplanted within the damaged muscle. Medium
      without cells was injected into an adjacent site to serve as a control. Endpoints
      comprised histology using standard stains as well as Masson trichrome (specific
      for connective tissue), and radioautography. In five dogs, satellite cell
      isolation, culture, and implantation were technically satisfactory. In three
      implanted dogs, specimens were taken within 6-8 wk. There were persistence of the
      implantation channels in the experimental sites when compared to the controls.
      Macroscopically, muscle tissue completely surrounded by scar tissue could be
      seen. Masson trichrome staining showed homogeneous scar in the control site, but
      not in the test site where a patch of muscle fibres containing intercalated discs
      (characteristic of myocardial tissue) was observed. In two other dogs, specimens
      were taken at 14 wk postimplantation. Muscle tissue could not be found. These
      preliminary results could be consistent with the hypothesis that SKM satellite
      cells can form neo-myocardium within an appropriate environment. Our specimens
      failed to demonstrate the presence of myocyte nuclei.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1344312
TI  - Hepatocyte immobilization on PHEMA microcarriers and its biologically modified
      forms.
AB  - Polyhydroxyethylmethacrylate (PHEMA) based microcarriers with different bulk
      structures were prepared by a phase inversion polymerization technique. PHEMA
      surfaces were further modified chemically by glow-discharge treatment, and
      biologically by covalent attachment of fibrinogen and collagen. Hepatocytes were
      isolated from young male Wistar rats using an in situ portal vein collagenase
      perfusion technique. Freshly isolated hepatocytes were seeded at 6 x 10(5)
      cells/mL and microcarrier concentration was 10 g/L. Stationary microcarrier
      cultures were carried out in standard (nontissue culture) polystyrene petri
      dishes in a humidified 5% CO2 incubator at 37 +/- 0.5 degrees C. Cell attachment
      was followed by light microscopy by taking samples from the culture medium every
      30 min. Urea and protein syntheses by microcarrier-attached hepatocytes were
      determined by standard techniques. Nonswellable (highly cross-linked) hydrophilic
      PHEMA microcarriers did not support cell attachment and viability. However,
      swellable (low cross-linked) PHEMA microcarriers (pretreated in FBS) allowed high
      attachment and cell spreading. PHEMA microcarriers treated in
      dimethylaminoethylmethacrylate (DMAEMA) glow-discharge plasma also improved the
      cell attachment characteristics of the PHEMA microcarriers. The highest
      attachment efficiencies (immobilization yields) were observed with the
      biologically modified PHEMA microcarriers, especially modified with fibronectin.
      Metabolic activity, as estimated by urea and protein syntheses, was also higher
      in these microcarriers.

PMID- 1344313
TI  - Behavioral effects of neural transplantation.
AB  - Considerable evidence suggests that transplantation of fetal neural tissue
      ameliorates the behavioral deficits observed in a variety of animal models of CNS
      disorders. However, it is also becoming increasingly clear that neural
      transplants do not necessarily produce behavioral recovery, and in some cases
      have either no beneficial effects, magnify existing behavioral abnormalities, or
      even produce a unique constellation of deficits. Regardless, studies
      demonstrating the successful use of neural transplants in reducing or eliminating
      behavioral deficits in these animal models has led directly to their clinical
      application in human neurodegenerative disorders such as Parkinson's disease.
      This review examines the beneficial and deleterious behavioral consequences of
      neural transplants in different animal models of human diseases, and discusses
      the possible mechanisms by which neural transplants might produce behavior
      recovery.

PMID- 1344314
TI  - False diagnosis of epilepsy in children.
AB  - Epilepsy is frequently diagnosed incorrectly through a failure to obtain an
      adequate history and placing inappropriate emphasis on the electroencephalogram
      (EEG). We describe four children with common, nonepileptic events who were
      diagnosed initially as having epilepsy.

PMID- 1344315
TI  - Diagnosis, management and prognosis of a group of 128 patients with non-epileptic
      attack disorder. Part I.
AB  - Three hundred and forty three patients with attack disorder labelled as epilepsy
      were admitted for assessment to a Neuropsychiatry ward in a small English mental
      hospital over a 5 year period. After assessment it was decided that 63% (215) of
      these patients had epilepsy, but in 128 (37%) a diagnosis of non-epileptic
      seizures was made. Just over a third of these patients (46) had an additional
      history of present or past epileptic seizures as well, so that 24% of the total
      population had non-epileptic seizures only. The methods used to make this
      diagnosis are reviewed and an attempt made to classify the non-epileptic attacks
      from which the patients were suffering. A variety of management strategies were
      offered and at discharge from hospital the majority of patients had practically
      lost their non-epileptic seizures. At follow-up 2 years later, seizures had
      returned in most patients. In 8% of the patients it was clear that the diagnosis
      of non-epilepsy had been erroneous. The importance of classifying the kind of non
      epileptic event the patient suffers from and of translating treatment in hospital
      to the community is emphasized.

PMID- 1344316
TI  - Diagnosis, management and prognosis of a group of 128 patients with non-epileptic
      attack disorder. Part II. Previous childhood sexual abuse in the aetiology of
      these disorders.
AB  - In a group of female in-patients clinically diagnosed as having non-epileptic
      attack disorder there was an increased incidence of a proven previous history of
      sexual abuse in childhood, when compared with a group of women with epilepsy and
      a group of women with other psychiatric disorders admitted to the same ward. This
      was particularly true of women with the 'swoon' and 'abreactive' type of non
      epileptic attack disorder (see Part I). The incidence of a history of previous
      abuse was similar to the two control groups for other types of non-epileptic
      attack disorder. The swoon was seen as a cut-off phenomenon: the abreactive
      attack as a kind of acting out the memory of the abuse, part of a post-traumatic
      stress disorder. Both may respond to counselling for the abuse although it is too
      early to be certain, and there is a risk of further episodes of the non-epileptic
      attack disorder during periods of stress. Some patients with epilepsy, however,
      also had a history of previous sexual abuse: in some the stress of the abuse may
      have precipitated the epileptic seizures.

PMID- 1344317
TI  - Clinical use of lamotrigine.

PMID- 1344318
TI  - Seizure behaviour in a patient with post-traumatic stress disorder following
      rape. Notes on the aetiology of 'pseudoseizures'.
AB  - A patient is described who began to have paroxysmal convulsive behaviour,
      followed by a post-ictal aggression, which was initially diagnosed and treated as
      epilepsy. The behaviour began after the patient was raped. She had many of the
      symptoms of post-traumatic stress disorder. It is suggested that the paroxysmal
      behaviour was an 'acting out' of intrusive and vivid memories of the rape, so
      called 'flashbacks'. Because the rape had occurred comparatively recently and the
      events that occurred during the rape were known, it was easy, in this particular
      patient, to understand the relationship between the previous trauma and the
      paroxysmal behaviour. The case throws some light on the relationship between
      similar paroxysmal behaviour in the victims of child sexual abuse and the trauma
      they had suffered and explains why they behave in the way that they do.

PMID- 1344319
TI  - Memory failure in epilepsy: retrospective reports and prospective recordings.
AB  - People with epilepsy frequently complain of memory difficulties and previous
      research provides some support for the existence of memory dysfunction. However,
      our clinical experience is that many who report serious memory difficulties
      perform quite adequately on psychometric tests. One explanation for this
      discrepancy is that these patients are exaggerating the difficulties they
      encounter in their daily lives. This study aimed to examine this hypothesis by
      comparing patients' retrospective reports of memory to prospective recordings of
      everyday memory failures. Results demonstrated that far from over-emphasizing
      their daily problems, people with epilepsy believed fewer memory failures
      occurred when rated retrospectively than was indicated by a prospective recording
      device. While there was good agreement between the methods of assessing memory
      failures for the frequency of their most troublesome difficulties, subjects
      tended to underestimate the incidence of the less pervasive everyday problems.
      The results are interpreted through the theory of memory introspection proposed
      by Herrmann.

PMID- 1344320
TI  - The impact of chronic epilepsy on the family.
AB  - The emotional impact of intractable epilepsy on family members is a neglected
      topic, with the majority of studies confined to childhood epilepsy. Our clinical
      experience suggests that family members, particularly parents, may at times be
      under considerable emotional strain, especially when seizures are frequent and
      accompanied by injury. The purpose of this study was to explore the psychological
      and physical well-being, satisfaction with social circumstances and perceived
      level of support in families with an adult member with intractable epilepsy.
      Forty-four families were administered rating scales of mood and answered
      questions relating to their social situation and physical health. Levels of
      stress and dissatisfaction with their social situation was high, particularly in
      primary carers (the mother in most instances). Respite periods away from their
      caring role were few and the perceived level of support was low. Poor emotional
      adjustment was associated with severity of tonic and atonic seizures and episodes
      of status. Additionally, perceived low levels of support were associated with
      depression.

PMID- 1344321
TI  - Some issues in the assessment of epilepsy occurring in the context of learning
      disability in adults.
AB  - Epilepsy is a common condition in people with learning difficulties. The
      assessment of seizure disorders in this group requires special consideration of
      psychological and social, as well as medical, aspects. We consider an integrated
      approach assessing epilepsy and learning difficulties in parallel. Such
      meticulous assessment can lead to improved quality of life with treatment
      changes, and will avoid unnecessary medical and social costs.

PMID- 1344322
TI  - What to do when the first anticonvulsant does not work.

PMID- 1344323
TI  - Non-epileptic seizures: management and predictive factors of outcome.
AB  - We report a prospective series of 18 patients with a diagnosis of non-epileptic
      seizures (NES, pseudoseizures) identified in one unit. Sixteen patients agreed to
      complete a therapeutic programme. At the end of treatment eight were seizure
      free, three had only occasional NES and five were unchanged. At 1-year follow-up
      the situation remained similar regarding seizures, with responders demonstrating
      an improvement in social functioning and a marked reduction in demands on health
      service resources. Admission variables significantly associated with a poor
      outcome were an IQ of less than 80 and a past history of violent behaviour.

PMID- 1344324
TI  - Epilepsy: patient views on their condition and treatment.
AB  - To determine how patients with epilepsy feel about their condition, their current
      medication and their treatment, a mail survey was conducted among a random
      selection of 800 members of the British Epilepsy Association (BEA). Completed
      questionnaires were received from 437 members (55% response rate). This high
      response rate, achieved over a 4-week period, indicates great concern about their
      condition among the membership sampled. The majority of patients (80%) were
      adults; 20% were 18 years or younger. Some 72% of patients experienced one or
      less seizures per month and 52% were employed. Comments from an open-ended
      question about treatment indicated that respondents would like to see an increase
      in the provision of services and in the information conveyed (a more interactive
      communication between the patient and the physician); both issues should improve
      the emotional support provided by physicians. Positive feelings about medications
      were reported when seizures were controlled, although unhappiness was expressed
      with the length of time and varying doses that had to be taken before a 'correct'
      dosage level was established. Also expressed was a concern about the extent of
      management and of experimentation with medication left to the patient and care
      giver. Opportunities exist for greater communication among physician, patient and
      care-givers to ease the feeling of frustration, discouragement and isolation seen
      with a condition which affects 2 to 3% of individuals during their lifetime.

PMID- 1344325
TI  - Predictive factors for controlling seizures using a behavioural approach.
AB  - A behavioural approach using EEG biofeedback for controlling complex-partial
      seizures has been successful at the Andrews/Reiter Epilepsy Research Program.
      Records for a random sample of 83 patients with uncontrolled seizures, one third
      of those receiving care between 1980 and 1985, document that 69 (83%) achieved
      control by completion of the programme. Additional data about initial age of
      seizure onset, number of years seizures had been uncontrolled and seizure
      frequency when treatment started were collected to determine whether these
      factors predicted seizure control. Only frequency was significantly related to
      whether seizures were controlled when treatment ended. Further study using
      discriminant analysis showed that earlier onset age and higher seizure frequency
      were associated with a significantly greater number of treatment sessions
      required. Thus, these two factors predicted difficulty in controlling seizures,
      as measured by number of sessions, although onset age did not predict whether
      control was eventually achieved. Since even the subgroup achieving the lowest
      rate of control (i.e., patients having daily seizures when treatment started) had
      67% success, these results suggest that a behavioural approach can be useful for
      many people with currently uncontrolled complex-partial seizures regardless of
      their characteristics on factors examined in this study.

PMID- 1344326
TI  - A review of interictal cerebral blood flow in the evaluation of patients for
      epilepsy surgery.
AB  - The literature on cerebral blood flow (CBF) studies in patients with epilepsy is
      critically reviewed. Two methods are specifically addressed, radioactive xenon
      delivered through inhalation or vascularly, and single photon emission computed
      tomography (SPECT) using various tracers. Both regional and global blood flow
      were used in these studies to assess focal and generalized seizures.
      Electroencephalogram (EEG) foci were determined by various techniques, including
      interictal and ictal recordings from scalp or intracranial electrodes. All
      studies reported a positive concordance between EEG foci and CBF. However, there
      was a high incidence of false positive and false negative results. The
      methodology of almost all of the studies was inadequate to assess accurately the
      sensitivity and specificity of CBF to localize the seizure focus. Even when
      conservative estimates were made, the sensitivity and specificity of CBF was too
      low to be used as a diagnostic test for epilepsy, and inadequate to localize the
      EEG focus in the evaluation of patients for epilepsy surgery.

PMID- 1344327
TI  - Employment among young people with epilepsy.
AB  - The study reports the findings of a follow-up review of 38 trainees who had
      completed social skills training programmes run by BRAINWAVE The Irish Epilepsy
      Association and FAS, the state training and employment authority, during the
      period 1986 to 1990. The social skills programmes were aimed at young,
      unqualified school leavers. A total of 101 young people completed the programmes,
      45 of whom had epilepsy. Of those with epilepsy, 38 were interviewed about their
      current employment position. On completion of the programmes 58% had found a job
      or gone on to further training. At the time of interview 39% were in work or
      training. Fifty-eight per cent were still experiencing seizures (a seizure in the
      last 12 months). Fifty per cent of those interviewed felt that they were being
      actively discriminated against because of their epilepsy. Fifty-eight per cent
      had made contact with the National Rehabilitation Board, the state placement
      service for people with a disability, but only 36% of these were in training or
      employment at the time of interview. Sixty-six per cent of those interviewed had
      found the programmes helpful in terms of increasing their self-confidence and
      social skills. The study points to the need for more specialized training and job
      placement programmes for young people with epilepsy.

PMID- 1344328
TI  - Knowledge of epilepsy among relatives of the epilepsy sufferer.
AB  - A 23-item questionnaire was constructed to assess awareness of basic facts about
      epilepsy. Close family members of the epilepsy sufferer achieved significantly
      higher scores on the questionnaire than individuals from families without
      experience of the condition. The questionnaire may be useful in the
      identification of family members of the epilepsy sufferer whose knowledge of the
      condition is low and who may require appropriate counselling.

PMID- 1344329
TI  - Exacerbation of typical absence seizures by progesterone.
AB  - Variation of seizure frequency during the menstrual cycle has been attributed in
      part to an antiepileptic action of progesterone reducing seizure frequency during
      the luteal phase, but studies have not distinguished patients with primary
      generalized, secondary generalized and absence epilepsies. We describe a patient
      whose absence seizure frequency increased when she was administered progesterone.
      This indicates that, in contrast to secondarily generalized seizures,
      progesterone may exacerbate absence seizures.

PMID- 1344330
TI  - Epilepsy, Europe and the patient.

PMID- 1344331
TI  - Sudden death and epilepsy.

PMID- 1344332
TI  - Fatal liver failure following generalized tonic-clonic seizures.
AB  - We present three cases of fatal hepatic necrosis in patients with epilepsy taking
      anticonvulsants, in which the terminal illness presented as an unusually severe
      generalized tonic-clonic seizure with failure to regain consciousness. In two
      cases acute renal failure also occurred. It is not certain to what extent drug
      therapy, physiological and metabolic changes consequent on prolonged seizures,
      hitherto undiscovered infective agents, or a combination of any of these may play
      in such a process. We suggest, however, that the case against the drugs alone has
      yet to be proved.

PMID- 1344333
TI  - Seizure circuit analysis with voltage sensitive dye.
AB  - Voltage sensitive dye was used to produce a map of average membrane polarization
      for the purpose of analysing the circuitry involved in seizures. Dorsal
      hippocampus, ventral hippocampus, entorhinal cortex, substantia nigra and
      occipital cortex were selected to calculate the relative changes in polarization.
      Rats were induced with bicuculline to have convulsive seizures and mild limbic
      seizures with kainic acid. A 20 second sample of these seizures were recorded
      using the voltage sensitive dye. Control animals showed a relatively uniform
      polarization state in the five brain areas. The bicuculline seizure produced
      hyperpolarization in all five areas. The magnitude of the hyperpolarization
      varied among the regions to produce a distinctive pattern. The kainic acid
      seizure produced depolarization in the four limbic areas. The magnitude of the
      depolarization also varied, producing a different pattern compared with
      bicuculline or control. Future applications of this technique in animal models
      could help identify those areas in the brain which regulate seizure propagation,
      and the anatomical loci in which antiepileptic drugs interfere with this
      propagation. Ultimately, human applications would include linking voltage
      sensitive dyes with paramagnetic or positron emitting traces so that epileptic
      processes could be visualized using magnetic resonance imaging or positron
      emission computed tomography.

PMID- 1344334
TI  - The occurrence, management and outcome of antiepileptic drug side effects in 767
      patients.
AB  - This study reports the nature of adverse drug reactions (ADR) occurring in 767
      epilepsy clinic patients (adults and children), the drugs most commonly involved,
      how they were managed and the outcome of such management. One hundred and thirty
      four patients were found to have 155 separate ADRs. The majority appeared to be
      pharmacodynamic in nature, although 21 were clearly pharmacokinetic in origin and
      four due to drug interactions. The antiepileptic drugs (AED) perceived to be
      causative, in order of frequency were phenytoin, sodium valproate, carbamazepine,
      clonazepam, barbiturates, vigabatrin and clobazam. Management most often involved
      withdrawing the offending drug(s), usually replacing them with another AED. Of
      the 155 ADRs, 40.6% resolved totally, 27.7% showed a marked improvement, 16.1%
      improved, 14.8% did not change and one patient deteriorated. This study
      emphasizes the need to be vigilant for ADRs and demonstrates that their
      management is essentially clinical with some 85% of patients experiencing
      benefit.

PMID- 1344335
TI  - Cerebral insult-like partial status epilepticus in the early-onset variant of
      benign childhood epilepsy with occipital paroxysms.
AB  - Nine children with the early-onset variant of benign childhood epilepsy with
      occipital paroxysms had protracted, cerebral insult-like, ictal episodes of
      impairment of consciousness, vomiting, tonic deviation of the eyes and hemi
      convulsions or generalized tonic-clonic seizures. Long term follow-up indicates
      that this is an entirely benign epileptic condition.

PMID- 1344337
TI  - [Japanese clinical statistical data of patients with chorea].

PMID- 1344338
TI  - [Japanese clinical statistical data of patients with parkinson's disease].

PMID- 1344339
TI  - [Japanese clinical statistical data of patients with Shy-Drager syndrome].

PMID- 1344341
TI  - [Japanese clinical statistical data of progressive supranuclear palsy].

PMID- 1344340
TI  - [Japanese clinical statistical data of patients with Spinocerebellar
      degeneration].

PMID- 1344342
TI  - [Japanese clinical statistical data of patients with subacute myelo-optico
      neuropathy].

PMID- 1344343
TI  - [Japanese clinical statistical data of patients with motor neuron disease].

PMID- 1344344
TI  - [Japanese clinical statistical data of patients with polyneuropathy].

PMID- 1344345
TI  - [Japanese clinical statistical data of patients with Guillain-Barre syndrome].

PMID- 1344346
TI  - [Japanese clinical statistical data of patients with Recklinghausen disease].

PMID- 1344347
TI  - [Japanese clinical statistical data of patients with progressive muscular
      dystrophy].

PMID- 1344348
TI  - [Japanese clinical statistical data of patients with myasthenia gravis].

PMID- 1344349
TI  - [Japanese clinical statistical data of patients with Eaton-Lambert myasthenic
      syndrome].

PMID- 1344350
TI  - [Japanese clinical statistical data of patients with periodic paralysis].

PMID- 1344351
TI  - [Japanese clinical statistical data of myotonic syndrome].

PMID- 1344352
TI  - [Japanese clinical statistical data of patients with benign essential
      hypertension].

PMID- 1344353
TI  - [Japanese clinical statistical data of patients with malignant essential
      hypertension].

PMID- 1344354
TI  - [Japanese clinical statistical data of hypertension in young adults].

PMID- 1344355
TI  - [Epidemiological study of cerebral infarction and transient cerebral ischemic
      attack in Japan].

PMID- 1344356
TI  - [Japanese clinical statistical data of patients with primary hypotension].

PMID- 1344357
TI  - [Japanese clinical statistical data of patients with angina pectoris].

PMID- 1344358
TI  - [Japanese clinical statistical data of patients with myocardial infarction].

PMID- 1344360
TI  - [Japanese clinical statistical data of patients with acquired valvular heart
      diseases].

PMID- 1344359
TI  - [Japanese clinical statistical data of patients with congenital heart diseases].

PMID- 1344362
TI  - [Japanese clinical statistical data of patients with cardiomyopathy].

PMID- 1344361
TI  - [Japanese clinical statistical data of patients with arrhythmia].

PMID- 1344363
TI  - [Japanese clinical statistical data of patients with pericarditis].

PMID- 1344364
TI  - [Acute pump failure in myocardial infarction].

PMID- 1344365
TI  - [Japanese clinical statistical data of patients with congestive heart failure].

PMID- 1344366
TI  - [Japanese clinical statistical data of patients with aortitis syndrome].

PMID- 1344367
TI  - [Epidemiological study of subarachnoid hemorrhage in Japan].

PMID- 1344368
TI  - [Japanese clinical statistical data of patients with aortic aneurysm].

PMID- 1344369
TI  - [Japanese clinical statistical study of patients with deep venous thrombosis].

PMID- 1344370
TI  - [Bronchial asthma].

PMID- 1344372
TI  - [Japanese clinical statistical data of patients with chronic obstructive
      pulmonary disease].

PMID- 1344371
TI  - [Japanese clinical statistical data of patients with diffuse panbronchiolitis].

PMID- 1344373
TI  - [Japanese clinical statistical data of patients with pulmonary tuberculosis].

PMID- 1344374
TI  - [Japanese clinical statistical data of patients with atypical mycobacterial
      disease (mycobacteriosis other than tuberculosis)].

PMID- 1344375
TI  - [Epidemiological study of spontaneous occlusion of the circle of willis in
      Japan].

PMID- 1344376
TI  - [Japanese clinical statistical data of patients with bacterial pneumonia].

PMID- 1344377
TI  - [Japanese clinical statistical data of patients with pneumocystis carinii
      pneumonia].

PMID- 1344378
TI  - [Japanese clinical statistical data of patients with viral pneumonia].

PMID- 1344379
TI  - [Japanese clinical statistical infections of patients with fungal infections].

PMID- 1344380
TI  - [Japanese clinical statistical data of patients with idiopathic interstitial
      pneumonia].

PMID- 1344381
TI  - [Pulmonary infiltration of eosinophilia].

PMID- 1344382
TI  - [Primary pulmonary hypertension].

PMID- 1344383
TI  - [Japanese clinical statistical data of patients with peptic ulcer].

PMID- 1344384
TI  - [Japanese clinical statistical data of patients with ulcerative colitis].

PMID- 1344385
TI  - [Epidemiological study of infantile intractable hydrocephalus in Japan].

PMID- 1344386
TI  - [Japanese clinical statistical data of patients with Crohn's disease].

PMID- 1344387
TI  - [Epidemiological study of cerebral bleeding in Japan].

PMID- 1344388
TI  - [Japanese clinical statistical data of patients with gastrointestinal polyp].

PMID- 1344389
TI  - [Epidemiological study of normal pressure hydrocephalus in Japan].

PMID- 1344390
TI  - [Japanese clinical statistical data of patients with malabsorption].

PMID- 1344391
TI  - [Japanese clinical statistical data of patients with protein-losing enteropathy].

PMID- 1344392
TI  - [Japanese clinical statistical data of patients with typhoid fever-paratyphoid
      fever and cholera].

PMID- 1344393
TI  - [Japanese clinical statistical data of patients with dysentery].

PMID- 1344394
TI  - [Japanese clinical statistical data of patients with bacterial food poisoning].

PMID- 1344395
TI  - [Epidemiological study of demyelinating diseases in Japan].

PMID- 1344396
TI  - [Japanese clinical statistical data of patients with Escherichia coli diarrhea].

PMID- 1344397
TI  - [Japanese clinical statistical data of patients with hepatitis type A].

PMID- 1344399
TI  - [Japanese clinical statistical data of patients with hepatitis C].

PMID- 1344398
TI  - [Japanese clinical statistical data of patients with hepatitis B].

PMID- 1344400
TI  - [The incidence of alcoholic liver disease in Japan].

PMID- 1344402
TI  - [Epidemiological study of Alzheimer's disease, Pick's disease and subcortical
      dementia in Japan].

PMID- 1344401
TI  - [Drug-induced hepatic injury--the review of the Japanese articles for the past 80
      years].

PMID- 1344403
TI  - [Japanese clinical statistical data of patients with fulminant hepatitis].

PMID- 1344404
TI  - [Japanese clinical statistical data of patients with Weil's disease].

PMID- 1344405
TI  - [Clinical statistical data of autoimmune hepatitis in Japan].

PMID- 1344406
TI  - [Clinical and statistical features of liver cirrhosis in Japan].

PMID- 1344407
TI  - [Japanese clinical statistical data of patients with constitutional jaundice].

PMID- 1344408
TI  - [Japanese clinical statistical data of patients with portal hypertension].

PMID- 1344409
TI  - [Japanese clinical statistical data of patients with cholelithiasis, biliary
      infection].

PMID- 1344410
TI  - [Japanese clinical statistical data of patients with acute pancreatitis].

PMID- 1344411
TI  - [Epidemiological study of tuberous sclerosis in Japan].

PMID- 1344412
TI  - [Japanese clinical statistical data of patients with chronic pancreatitis].

PMID- 1344413
TI  - [Japanese clinical statistical data of patients with cystic fibrosis].

PMID- 1344414
TI  - [Japanese clinical statistical data of patients with aplastic anemia].

PMID- 1344415
TI  - [Japanese clinical statistical data of patients with congenital hemolytic
      anemia].

PMID- 1344416
TI  - [Japanese clinical statistical data of acquired hemolytic anemia].

PMID- 1344417
TI  - [Japanese clinical statistical data of patients with refractory anemia].

PMID- 1344418
TI  - [Slow virus infection: the Japanese clinical statistical data].

PMID- 1344419
TI  - [Japanese clinical statistical data of patients with pernicious anemia].

PMID- 1344420
TI  - [Japanese clinical statistical data of patients with megaloblastic anemia due to
      folic acid deficiency].

PMID- 1344421
TI  - [Japanese clinical statistical data of patients with pyridoxine deficiency
      anemia].

PMID- 1344422
TI  - [Japanese clinical statistical data of patients with agranulocytosis].

PMID- 1344423
TI  - [Clinical statistical data of patients with abnormal hemoglobin].

PMID- 1344424
TI  - [Japanese clinical statistical data of patients with polycythemia vera].

PMID- 1344425
TI  - [Japanese clinical statistical data of patients with acute leukemias].

PMID- 1344426
TI  - [Japanese clinical statistical data of patients with chronic leukemia].

PMID- 1344427
TI  - [Japanese clinical statistical data of patients with adult T-cell leukemia].

PMID- 1344428
TI  - [Japanese clinical statistical data of patients with plasma cell dyscrasia with
      polyneuropathy and endocrine disorder].

PMID- 1344429
TI  - [Japanese clinical statistical data of patients with idiopathic thrombocytopenic
      purpura].

PMID- 1344430
TI  - [Clinical statistical data of patients with hemophilia and related diseases].

PMID- 1344431
TI  - [Disseminated intravascular coagulation].

PMID- 1344432
TI  - [Hodgkin's disease].

PMID- 1344433
TI  - [Clinical statistical data of patients with non-Hodgkin's lymphoma].

PMID- 1344434
TI  - [Japanese clinical statistical data of meningitis].

PMID- 1344435
TI  - [Treatment of retinal detachment using pneumatic retinopexy].
AB  - A series of 46 eyes with idiopathic rhegmatogenous retinal detachment, treated by
      pneumatic retinopexy has been reviewed. Of 46 eyes 8 were aphakic and 3
      pseudophakic. In 4 eyes proliferative vitreoretinopathy was preoperatively
      present. Anatomic success was achieved in 59% of cases after follow-up of 6-26
      months. With additional operations (conventional and/or vitrectomy) anatomical
      success rate was increased to 98%.

PMID- 1344436
TI  - [10 years' experience with the use of endoscopy in the intraoperative diagnosis
      of extrahepatic biliary tract diseases].
AB  - In the last ten years 375 patients were operated on biliary tract examined with
      intraoperative choledochoscopy. Sensitivity of choledochoscopy in our
      investigation was 72% and negative predictive value was 85% while specificity and
      positive predictive value for flexible choledochoscopy was 100%. There were no
      false positive results. After the instrumental exploration of the common bile
      duct, unsuspected stones were found in 9.19% of patients recorded with
      choledochoscopy and 3.44% of retained stones confirmed by postoperative
      cholangiography. Choledochoscopy was successful in determination of the level of
      obstruction by tumors in all patients (100%), but of limited value in
      determination of tumor extension through the bile duct wall in 66.66% of
      patients. Interventional procedures through the work channel of the instrument
      showed little success. Extraction of impacted stones was recorded in one patient
      (3.70%) while the biopsies were completely unsuccessful. We recommend
      choledochoscopy for each patient with open common bile duct, especially with
      proved multiple common bile duct stones.

PMID- 1344437
TI  - [The role of Epstein-Barr viruses as etiologic agents in the mononucleosis
      syndrome].
AB  - Mononucleosis syndrome represents a number of symptoms with different etiology
      and pathogenicity with similar clinical features. The aim of the study was to
      investigate etiologic structure of mononucleosis syndrome, effects of etiologic
      factors and age on the severity of clinical features, clinical forms of the
      disease, complications and the outcome. The investigation was conducted in 46
      patients treated at the Clinic who had been diagnosed as having mononucleosis
      syndrome. EBV-IM was confirmed in 43%, adenoviral IM in 13%, while in 44% of the
      patients etiology of the disease was not established. In both groups more severe
      forms were present in patients over 16 years of age, but more frequently in EBV
      IM than in other patients with mononucleosis syndrome (40% vs 19.23%).
      Complications in the form of acute hepatitis were found only in patients with EBV
      IM in 20% of the cases, mean age 17 years. We are of the opinion that EBV is a
      significant etiologic agent in mononucleosis syndrome, that the disease is more
      severe in older patients who also develop complications. The outcome for all the
      patients was favorable.

PMID- 1344438
TI  - [Fatty material in the adrenal cortex 2 months after cessation of contamination].
AB  - The presence of lipid substances in the rat adrenal cortex was analysed two
      months after ending a one-month exposure to detergents. An increased quantity of
      neutral lipids was found throughout the adrenal cortex. An augmented triglyceride
      content was manifested to a higher degree in adrenocorticocytes. The largest
      quantity of phospholipids was observed in the adrenal cortex. The changes in the
      quantity and quality of lipid substances were described, which all testified to a
      stimulated activity of adrenal gland.

PMID- 1344439
TI  - [Atypical symptomatic headache in the developmental period--case report].
AB  - The authors report a case of atypical symptomatic headache in developmental age.
      It is a complex headache in which three etiologic factors are permeated and
      superposed. The basic mechanism is connected with the presence of vascular
      congenital malformation (a. trigemini primitiva persistens), second mechanism is
      associated with immunologic events (leucopenia-dyshematopoiesis) in which central
      nervous system is secondarily involved with headaches partly superposed and
      personality features mildly neurotic, which would represent the third etiologic
      factor. Since it is the case of symptomatic headache as a notorius clinical
      entity but with peculiar, puzzling, atypical clinical features and course, the
      authors point to the complexity of this type of headache, diagnostic speculations
      and difficulties encountered in therapeutical approaches.

PMID- 1344440
TI  - [Hypophyseal pseudomacroadenoma in primary hypothyroidism--2 case reports].
AB  - Primary hypothyroidism is often accompanied with hyperprolactinemia and if the
      untreated disease persists longer hypophyseal adenoma consisting of thyreotropic
      cells might develop. On the other hand, although rarely, simultaneous occurrence
      of primary hypothyroidism and hypophyseal prolactin adenoma might be encountered.
      If substitutional therapy, after the establishment of euthyroid status, does not
      eliminate clinical signs of hyperprolactinemia and normalize prolactin levels, a
      decision can be made in favor of hyperprolactinemia within primary
      hypothyroidism. In that case possible tumor changes in the hypophysis will show
      regressive tendency towards final disappearance. However if clinical signs and
      hyperprolactinemia persist after the establishment of euthyroid status,
      especially if accompanied with compressive signs this should be regarded as a
      coincidence of primary hypothyroidism and hypophyseal prolactin tumor. We report
      two female patients with primary hypothyroidism and hypophyseal
      pseudomacroadenoma.

PMID- 1344441
TI  - [Inhibition of initial puerperal and postabortion lactation using oral
      prostaglandin E2 (Dinoprostone)].
AB  - Authors present their experience in oral administration of Prostaglandin E2
      (Dinoproston, Upjohn) during postpartal and postabortal period (a 0.5 mg after
      legal pregnancy interruption) in suppression of lactation. Indications for
      postpartal lactation suppression were such as: stillbirth, postpartal neonatal
      death and maternal negative attitude towards breast feeding. The patients in whom
      the suppression of lactation was applied were of generative age (18-40 years)
      either primiparas or multiparas. All were delivered vaginally with no extra
      intrapartal or postpartal complications being the same in legal pregnancy
      interruptions which were performed by application of intravaginal, intracervical
      and intramuscular Prostaglandin preparations. The patients were administered 1
      tbl od 0.5 mg Dinoproston preparation every 6-7 hours, 48 h after the delivery,
      i.e. 2 tbl in total (after meal). This method of lactation suppression was
      applied in 50 patients during 1990. Satisfactory results were achieved in all
      cases, while negative side effects and complications were not noted. Oral
      administration of PGE2 was found very efficient in postpartal and postabortal
      lactation suppression while compared with previously applied methods such as
      Estrogen-Testosterone preparation, i.e. small doses of Bromergon applied during
      10-14 days. Oral administration of PG2 is more efficient and in a certain way
      more comfortable in relation to the previously applied methods.

PMID- 1344442
TI  - [Dosimetric measurements and early complications in patients with differentiated
      thyroid carcinomas treated with radioactive iodine].
AB  - The aim of the study was to determine the exposure dose rate during the
      application of radioiodine therapy (ablative or tumoral dose) given in order to
      treat the differentiated thyroid carcinoma, during the medical visit and
      examinations of those patients, to establish the safety distance from patients
      both for population and for medical staff and to perceive early complications
      after the therapy. The dosimetric measurements were performed in 10 patients. The
      exposure dose rate during the application of the therapy ranged from 2000 to
      10000 pC/kg.s, during the visit from 528 to 15 pC/kg.s and during the
      examinations of patients from 5500 to 200 pC/kg.s. The average safety distance
      from patients for population was about 8.5 m on the day O (the very day of the
      therapy) and 2.0 m on the day 4, while for the medical staff it amounted to 5.0 m
      on the day 0 and 0.5 m on the day 4. The early complications perceived were as
      follows: radiation thyroiditis in 5/10 patients, stomach problems in 1/10
      patients and transitorial leucopeny, forty days after the therapy, in 2/10
      patients.

PMID- 1344443
TI  - [Multimodal evoked potentials and the blink reflex in patients with primary
      brainstem lesions].
AB  - In 17 patients with primary brainstem injury, out of 60 patients with severe head
      trauma, diagnostic and prognostic values of multimodal evoked potentials and
      blink reflex were evaluated in relation to clinical syndromes of the brainstem,
      the duration of coma and the outcome. Clinical classification of the brainstem
      syndromes according to Gerstenbrand and Rumpl was used for the evaluation of the
      clinical findings, the Innsbruck Coma Scale (ICS) for the evaluation of the coma
      level, and the Glasgow Outcome Scale (GOS) for the outcome. Analyses and
      measurements of the multimodal evoked potentials and blink reflex were used many
      times in the period of assessment (six months after the injury). The analysis of
      our results with multimodal evoked potentials and blink reflex revealed different
      correlation and sensitivity in relation to the clinical syndromes of the
      brainstem, the duration of coma and the outcome of the injury. The blink reflex
      and somatosensory evoked potentials had the best correlation and the greatest
      sensitivity, the auditory evoked potentials had somewhat, while the visual evoked
      potentials had none. Multimodal evoked potentials and blink reflex increase the
      specificity of the diagnosis of brainstem injury compared to clinical observation
      only, and improve prognostic reliability.

PMID- 1344444
TI  - [Abdominal typhus today].
AB  - Abdominal typhus is all the rearer disease among acute infectious diseases in
      Vojvodina. In the last ten years (1981-1990) 16 patients with abdominal typhus
      were treated at the Department of Infectious Diseases in Novi Sad, mostly young
      individuals from 6 to 30 years of age (13 patients). Positive epidemiologic
      features were found in 13 patients. In 80% of the cases the source of infection
      was outside Vojvodina. They usually were admitted at the Department on the first
      and second week of the disease (11 patients), and 3 patients were admitted on the
      third week. None of the patients was suspected of having abdominal typhus at the
      time of admittance. Delayed hospitalization and unrecognized abdominal typhus
      were most likely due to the atypical onset and course of the disease. Atypical
      features in the clinical picture occurred in all the patients with a sudden onset
      of the disease. The abrupt temperature elevation in 50% of the patients was
      followed by shivering, fever and shaking. Hepatosplenomegaly was found in 12
      patients, abdominal meteorism in 10, typical typhus tongue in none. Typhus state
      was not found in any of the patients. Normal leucocyte count was found in 7
      patients, positive Widal's agglutination reaction in 13, coproculture in 8 and
      hemoculture in 15 patients. The atypical clinical picture was the result of early
      administration of broad-spectrum antibiotics before the established etiology of
      the febrile state.

PMID- 1344445
TI  - [Antibody titer levels and the presence of herpes simplex virus antibodies in the
      serum in relation to gender].
AB  - We examined 600 serum samples from female patients for the presence of antibodies
      to herpes simplex virus (RVK). 293 serum samples belonged to males and 291 to
      females, while in 25 carcinoma of female genital organs (cervix, endometrium,
      ovarium) was verified. Antibodies to HSV were found in 117 samples of which 68
      were taken from females, 29 from males. Out of 25 malignant cases 20 were
      positive to HSV antibodies. In the majority of samples only so called "anamnestic
      titre" 1:8 was proven while higher titres were more frequently found in females.
      Titre of 1:16 was detected in 27 females compared with 11 in males. Titre of 1:64
      was detected only in 2 females. Of 25 female serum samples with malignant
      precesses in genital organs 20 were positive, titres being above 1:8 except in 4
      cases.

PMID- 1344446
TI  - [Postspinal headache as an anesthesiology problem].
AB  - Spinal anaesthesia, is nowadays one of the safest anaesthetic techniques with low
      complication rates. Postspinal headache is a complication of spinal anaesthesia.
      This paper presents several factors associated with the development of postspinal
      headache and discusses the reduction, prediction and treatment of postspinal
      headache.

PMID- 1344447
TI  - [Diabetic retinopathy and other complications of diabetes mellitus].
AB  - The paper reviews the results of a ten-year follow up conducted in 140 diabetic
      patients at the Ophthalmology Clinic in Novi Sad. We analysed the number of the
      cases and ratios between diabetic retinopathy and other complications in eyes and
      other organs. Apart from retinopathy among eye diseases the most frequent was
      hypertonic fundus in 20%, cataract in 17% of the eyes and occlusive conditions in
      the retinal blood vessels in 2.6%. In the whole group only 8% of the examined
      eyes had no changes. Complications develop in 70% of diabetics with retinopathy
      and 48% of those without retinopathy. Nephropathy was found in 18% of diabetics
      with retinopathy and 13% of those without it. Macroangiopathy of the brain, heart
      and peripheral blood vessels was found in lower percentage but more frequently in
      diabetics with retinopathy.

PMID- 1344448
TI  - [Smoking--II. Duration of smoking and factors affecting smoking as a social
      phenomenon].
AB  - According to the poll of 5,555 individuals (91% of the expected number) over 40
      years of age, selected from electoral registers in all three districts of the
      community of Mali Idjos in 1987, the average duration of smoking among active
      smokers increases with age, divergently with regard to sex. The age of smokers at
      the time they started smoking increases with age groups, from 22.2 to 33.2 in
      males and from 28.1 to 49 in females. The onset of smoking in the oldest male
      group in this rural area occurred in the first years after the war (first land
      confiscation) while in the group from 70 to 74 years of age it occurred in the
      years of compulsory crop-purchase system. Agglomeration in the onset of smoking
      in two male age groups (60-64, 65-69) occurred at the time of the second land
      confiscation. The onset of smoking among females from all age groups, from 45
      years on occurred in the first decade of the sexual revolution (1961-1971). The
      prevalence of smoking in the studied population was different in previous decades
      as well. It changes according to social factors: from political and economic
      changes among males to the changes in women's social status among females.

PMID- 1344449
TI  - [Prognostic significance of morphologic and morphometric characteristics of
      communicating hydroceles in boys].
AB  - The paper reviews the results of a prospective study on external morphologic
      characteristics of communicating testicular hydrocele in boys, which might help
      the prognosis of future events in the peritoneal testicular covering. We examined
      216 cases of communicating hydrocele and controlled their size and consistency
      every 3 months throughout the period of 15 months. It has been found that bigger
      hydroceles of about 3 x 3 cm which are always followed by the development of
      strained walls, remain in higher percentage unobliterated up to the 15th month of
      life, because of which an indication for surgical treatment is necessary (34.2%).
      More numerous were hydroceles exceeding 3 x 3 cm in children delivered before the
      40th gestational week.

PMID- 1344450
TI  - [Balneotherapy and bathing spas in Vojvodina].

PMID- 1344451
TI  - [Cytometric study of blast cells in acute leukemias and their prognostic value].
AB  - Cytometric assessment of the leukemic blasts was performed in the course of
      diagnosing acute leukemia. The results of the cytometric study were used as
      prognostic parameters. We measured the surface of the nucleus and of the
      cytoplasm, and calculated the nucleus-cytoplasm ratio. The investigation was
      carried out on peripheral blood and bone marrow smears in 50 patients with acute
      leukemia, classified according to the FAB classification. The results showed that
      the mean surface of the nucleus in all groups was significantly bigger in bone
      marrow cells than in the peripheral blood. In non-lymphoblastic leukemia no
      significant differences of the mean leukemic blast nucleus surface were found
      among the subgroups either in the bone marrow or in the peripheral blood.
      Concerning the mean surface of the blast cytoplasm in the peripheral blood it has
      been established that in the subgroup M-2 it is significantly the smallest in
      nonlymphoblastic leukemia subgroups, while in the bone marrow it is significantly
      bigger in M-2 and M-4 subgroups than in the peripheral blood. In lymphoblastic
      leukemia the mean surfaces of the cytoplasm in the peripheral blood were not
      significantly different from those in the bone marrow, while concerning the mean
      surface of the nucleus the difference was registered in favor of the bone marrow.
      The nucleus-cytoplasm ratio was rather high in the blasts of the peripheral blood
      and the bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1344452
TI  - [The effect of clonazepam on experimental epilepsy induced by
      electrostimulation].
AB  - The investigations were aimed at the study of effects of preparations which
      belong to the benzodiazepine group-Clonazepam (CZ), on total bioelectric activity
      (EEG) and epileptic discharge induced by electrostimulation of the hippocampus in
      the experimental animals (awake adult rabbits). Clonazepam was administered both
      intramuscularly (i.m.) and intravenously (i.v.) at a dose of 0.2-2.5 mg/kg of the
      body mass. The obtained results show that the administration of clonazepam
      prolongs the duration and the arrangement of the spindle in the bioelectric
      activity in rabbits and stops epileptic attacks of the grand mal type.

PMID- 1344453
TI  - [Diagnostic significance of preoperative determination of CA-125 serum levels in
      the differentiation of malignant and benign pelvic masses].
AB  - Preoperative estimation of serum C-125 tumour marker was performed in 45 patients
      with adnexal malignancies, 50 patients with benign pelvic masses and in 30
      healthy women who underwent plastic surgery for disturbed statics of genital
      organs. Elevated serum CA-125 values (above 65 U/ml) were observed in 38 (84.5%)
      patients with ovarian malignancies (chi = 355.93, SD +/- 251.86) and in 7 (14%)
      patients with palpable benign pelvic masses (chi = 48.09, SD +/- 77.08).
      Preoperatively evaluated serum CA-125 values were not evident in the control
      group (chi = 7.20, SD +/- 6.98). There were statistically significant differences
      (T = 8.13, p < 0.05) between preoperative mean serum CA-125 values in the
      patients with malignant and benign pelvic masses. Also, there was statistically
      significant difference between the control group, the group with malignancies (T
      = 7.48, p < 0.05) and the group with benign pelvic masses (T = 2.86, p < 0.05).
      Preoperative assessment of the serum CA-125 values proved to be significant but
      not absolutely reliable laboratory-diagnostic parameter in differentiation of
      malignant and benign pelvic masses in the female.

PMID- 1344454
TI  - [Stereologic analysis of the human hypoglossal nucleus during the period ranging
      from the 22nd postovulatory week until birth].
AB  - The hypoglossal nucleus consists of the cells of the fourth stage of maturation
      according to Rakic. However, there are obvious differences and one of them is
      observable in the degree of staining intensivity of their Nissl bodies and
      nuclear inclusions. The stereological analysis revealed a constant decreasing of
      numerical density of the nerve cells nuclei in stages investigated. The decrease
      of the numerical density was highly significant (p < 0.001), probably due to the
      tissue growth and the total increase of nucleus i.e. its neuropi. The shrinkage
      of the tissue must be taken into consideration, too.

PMID- 1344455
TI  - [Rhabdomyosarcomas in otorhinolaryngology].
AB  - The study reports two patients with very rare tumors, rhabdomyosarcomas. The
      first case was a six-year-old girl with tumor in the right nostril and
      epipharynx, the second was a 66-year-old male patient with protuberances in the
      hypopharynx. The diagnosis was based on the PH analysis. One case was treated
      with air therapy, the other was surgically treated. Both died soon after, the
      fact that points to an enormous malignant potential and unfavorable prognosis for
      the diseased.

PMID- 1344456
TI  - [Intraosseous schwannoma].
AB  - Neurogenic tumors, primary bone tumors, are rather exceptional; about 50 cases
      have been reported so far. The study reports a case of intraosseous schwannoma, a
      primary bone tumor, in a 20-year-old male patient, localized in the distal end of
      the right tibia.

PMID- 1344457
TI  - [Psychological characteristics of obese persons with special reference to periods
      of modified fasting].
AB  - It is well known fact that the results of modified fasting can be improved if the
      basic therapeutic method is combined with psychotherapeutic procedures. We have
      analyzed the data taken by a poll from 55 extremely obese women treated by
      modified fasting regimen. The results absolutely justify the above mentioned
      remark that radical reduction cures may cause critical moments most frequently
      recognized in hunger crisis when patients feel a need for conversion with medical
      staff. With no doubt, any help from a qualified person might be perfectly
      beneficial. Besides, obese persons are more inclined to depressive moods which
      may aggravate during these cures. In order to maintain the achieved result for a
      longer period of time if not for good, a continuous team work which include
      psychotherapeutic measures is of special significance. On the highest level it
      would be smart to establish an association of treated obese people, which would
      be a link between a patient and a professional.

PMID- 1344458
TI  - [Treatment of post-traumatic hemarthroses of the knee and ankle in children using
      transcutaneous electric nerve stimulation].
AB  - TENS (transcutaneous electric nerve stimulation) was applied in 36 children with
      knee or ankle hemarthros. Pain was diminished after first or second treatment and
      completely disappeared at the end of the first or second day. Swelling usually
      disappeared in the interval between the third and seventh day. At the end of the
      treatment joint movement was significantly improved. In the control group who
      received only conventional conservative treatment (puncture, immobilization or
      inactivity, drugs) swelling and pain were still present after the seventh day and
      these patients needed additional physiotherapy for next seven days. We consider
      the TENS a method of choice in the treatment of posttraumatic hemarthros
      providing that treatment starts immediately after the injury and that it is
      continually applied during 3-5 days. The patients are advised to use crutches. It
      is a simple, painless method which is not combined with any additional treatment.
      Proteolytic ointments can increase and stimulate the therapeutic effects.

PMID- 1344460
TI  - [Serum ionic calcium in the early neonatal period in premature and small-for
      gestational-age infants].
AB  - We determined the value of serum ionic calcium in premature infants of different
      gestational age and infants small for gestational age, on the first and the 3rd
      day after the birth. The aim of the study was to determine the incidence of
      hypocalcemia and to confirm the hypothesis that the food for newborns should be
      calcium supplemented which would prevent poor postnatal bone mineralization. The
      subjects were divided into two groups: premature infants from 28 to 32 and from
      32 to 36 gestational weeks. The third group consisted of intrauterine retarded
      newborns. The highest ionic calcium level was found in the intrauterine retarded
      newborns (1.30 on the first and 1.025 on the third day). High percentage (30%) of
      hypocalcemia was detected in premature infants from 28 to 32 gestational weeks.
      The high percentage of hypocalcemia in premature infants of smaller gestational
      age points to the need for calcium supplemented food which would prevent poor
      postnatal bone mineralization.

PMID- 1344459
TI  - [Hemorheologic changes in patients with essential hypertension treated with
      prazosin].
AB  - Prazosin which is a selective alfa-1 blocking drug has a very good
      antihypertensive effect. Its hemorheological effects were studied in 20 patients
      with essential hypertension (I and II degree according to WHO classification).
      After 6 weeks of the therapy with prazosin, hematocrit and viscosity of the whole
      blood and plasma were significantly reduced, because of hemodilution, while
      aggregability of erythrocyte and "Tk" values were not significantly reduced.
      Platelet aggregation induced by collagen, ADP and adrenaline, showed a decrease
      after the treatment. Assuming the hemorheological effects not to be crucial in
      choosing an antihypertensive agent, we must not, however, neglect them,
      especially in patients with compromised hemorheological profile, and we should
      take advantage of the positive hemorheological effect of prazosin, particularly
      in a long antihypertensive treatment.

PMID- 1344461
TI  - [Surgical treatment of perforating eye injuries due to intraocular foreign
      bodies].
AB  - Twenty-three consecutive cases of perforating ocular injuries with retained
      intraocular foreign body (IOFB) are examined in this retrospective study. The
      group most affected was that of males with mean age of 32 years, who sustained a
      job injury, presenting with a single corneal laceration. Of the 23 cases with
      injuries 22 (95%) were due to metallic foreign bodies. Of these, 12 (54%)
      involved foreign bodies of ferromagnetic origin. At surgery 14 (61%) of the 23
      IOFB were removed with forceps and 9 (39%) with electromagnet. From these
      patients 87% obtained visual acuity equal or better than that on admission.

PMID- 1344462
TI  - [Clinical manifestations of spinal lesions in dysraphic malformations of the
      caudal neuropore in children].
AB  - Disorders in the development of the spine and the spinal cord in the caudal
      neuroporus region significantly contribute to the morbidity and the lasting
      invalidity of children. Clinical investigations of the malformations manifest
      through different forms of body abnormalities, ranging from asymptomatic forms of
      "spina bifida occultae" to the severe forms of open "meningomyelocele". The
      nature and the level often cannot be detected before the development of the
      structural changes in the course of growth and development of the child, which
      can hardly be treated later. At the Department of Child Surgery in Novi Sad 12
      infants were surgically treated in the last 5 years, while 30 children were
      surgically and conservatively treated after the detection of the clinical and
      subclinical manifestations of dysraphism. The indications for the surgical
      treatment were open meningomyelocele as well as those subclinical forms
      indicating the development of the tethered corn syndrome, hydrocephalus and
      tumefactions in the lumbosacral region. Moreover the study points to the
      significance of certain clinical features and investigations in the diagnosis of
      spinal dysraphism.

PMID- 1344463
TI  - [Breech presentation terminated by cesarean section].
AB  - The prospective study was carried out in 86 mothers and their newborns born in
      breech presentation; 41 were delivered by cesarean section, 45 vaginally. The
      incidence of prepathologic and pathologic CTGs was rather high in both groups
      (34.14% and 24.34%) as well as the presence of meconium in the amniotic fluid
      (34.15% and 22.22%). The infants delivered by cesarean section have significantly
      (p < 0.05) higher pH levels (7.28 +/- 0.068) than those delivered vaginally (7.25
      +/- 0.093). The acidosis incidence (pH +/- 7.20) is significantly (p < 0.01)
      lower in the first (9.76%) than in the second (26.66%) group. In the early
      neonatal period 24.35% of the children in the first group and 35.55% of the
      children in the second group developed a disease (p < 0.05). The difference in
      the morbidity rate can also be found in the fact that in the studied group no
      intracranial hemorrhage was diagnosed while in the control group it was found in
      17.77% of the children. Manifest cerebral disfunction syndrome was detected in
      2.44% of the children delivered by cesarean section and in 8.88% of the children
      delivered vaginally. One child (2.22%) delivered with manual help has died. The
      morbidity of the mothers was significantly (p < 0.05) higher in women who gave
      birth abdominally (17.68%) than in those who gave birth vaginally (8.88%).

PMID- 1344464
TI  - [Patellar height in patients with chondromalacia].
AB  - A radiogrametric assessment of the patellar height performed by three measurement
      methods, in the lateral views of radiograms of 136 patients with chondromalacia
      of the patella was aimed at the establishment of certain parameter values in the
      studied population and the assessment of the influence the altered patellofemoral
      ratio has upon the onset of the disease. The results of the study verified the
      remarkable advantages of the method by Insall and Salvati for the measurement of
      the patellar height and showed a significant involvement of patellofemoral
      incongruity in the development of chondromalacia, since in 15-16% of the cases
      the patella was not properly placed.

PMID- 1344465
TI  - [Prophylaxis and therapy of infections in allogenic bone marrow transplantation
      in patients with hematologic diseases].
AB  - Infection and acute graft versus host disease (GVHD) are the most common
      complications of allogeneic bone marrow transplantation, which compromise this
      therapeutical method for hematologic diseases. Beside the appreciation of
      customary preventive measures and the treatment of infections, it is necessary
      for every bone marrow transplantation center to analyze the development of
      bacterial, fungal and viral infections in the patients and to generate the most
      efficient and most rational program for their prevention and treatment. At the
      Hematology Department in Novi Sad seven allogenic bone marrow transplantations
      were performed in patients with malignant hematologic diseases and severe form of
      aplastic anemia. Prevention of the infection by isolation of the patient in a
      sterile unit, selective decontamination of the digestive tract with sterile food,
      skin and mucus hygiene and prophylactic drug administration proved rather
      beneficial and adequate for patients with the graft accepted, hematopoiesis
      recovered and immunity reconstructed. Risks of infections were increased by
      permanent vein catheter, acute GVHD and rejection of the bone marrow graft.
      Prompt isolation and identification of bacteria and fungi, especially in blood,
      the establishment of a minimal suppressing and bactericide antibiotic
      concentration, along with the assessment of their synergism, as well as early
      diagnosis of cytomegalovirus and administration of specific drugs, can
      significantly contribute to the more successful treatment of infections in
      transplanted patients.

PMID- 1344466
TI  - [Standard histopathologic criteria in intraoperative diagnosis of thyroid gland
      diseases].
AB  - The objective of intraoperative histological diagnostics of thyroid gland
      diseases using the tissue freezing method is planning the appropriate surgical
      scope at the time of operation. This necessitates maximal diagnostic accuracy
      having in mind the fact that freezing changes the tissue structure resulting in
      numerous technical defects in the histological preparation. These defects can be
      eliminated by multiplying histomorphological criteria, accurate explanation of
      their significance and interdependency and by making a conclusion in the form of
      ex tempore diagnosis. We studied 88 cases of ex tempore diagnosed changes in the
      thyroid gland using 15 different morphological criteria. The adjustment of the
      metrics scale to arithmetic progression enabled us to use certain number of
      parametric tests. A universal approach along with non-parametric methods with
      highly significant results made it possible to evaluate histomorphological
      criteria which can be regularly used in intraoperative diagnostics of
      pathological changes in the thyroid gland.

PMID- 1344467
TI  - [The effect of chronic alcohol administration on specific features of the
      adenohypophysis in young animals in relation to the adult adenohypophysis].
AB  - We investigated chronic effects of ethyl alcohol on adenohypophysis in adult
      Wistar rats and adenohypophysis in development including the postnatal period up
      to 30 days. Morphological findings in gonadotropic, prolactin and follicular
      cells were compared. After three months of constant alcohol consumption in the
      form of a 15% liquid solution, vacuolization of gonadotropic cells which acquire
      the shape of a seal ring, as well as nodular hyperplasia of chromophobe cells
      combined with sparse somatotropic cells, occur in the adenohypophysis of adult
      male rats. Electronic microscope revealed a small quantity of prolactin granules
      in light-microscopic chromophobe cells. In young rats exposed to alcohol
      gonadotropic and prolactin cells are unchanged but an accumulation of follicular
      cells within multiple smaller pseudofollicles is present. In the explanation of
      the differences between the findings obtained in adult and young rats with
      reference to LH/FSH and PRL cells, a stress is given to the role of the
      peripheral metabolism of testosterone and of hyperestrogenemia caused by alcohol
      consumption in adult rats lacking in young ones. The increased number of the
      follicular cells in adenohypophyses of young rats is likely to reflect the
      suppressed maturation of hypophyseal secretory cells.

PMID- 1344468
TI  - [Hereditary sensory-motor polyneuropathy. Case report and problems in
      differential diagnosis].
AB  - The study reports a family in which three children were found to have marked
      sensory-motor polyneuropathy. Clinical investigations revealed a recessive
      hereditary form of highly progredient mostly motor polyneuropathy with atrophy
      and weakness of distal muscle groups and electrophysiologic evidence of
      neurogenic lesion-delayed neural conduction. Apart from the peripheral nerves,
      clinical examination and additional investigations showed that the degenerative
      process encompassed central nerve system structures, posterior bundles of the
      spinal cord, spinal cerebral pathways, cerebellum and cerebrum (cerebral sings,
      mental retardation, epilepsy, brain atrophy on CT, increased IGG in the liquor
      are present). Although clinical and electrophysiological analyses suggest type
      III HSMN, muscle and nerve biopsy, as well as additional diagnostic methods
      broaden the differential diagnostic range toward other forms of hereditary
      polyneuropathy, whose differentiation in practice is, in spite of clear
      diagnostic criteria, rather difficult, due to the presence of its transitive
      forms.

PMID- 1344469
TI  - [Favre-Racouchot syndrome: case report].
AB  - The authors present a case of Favre-Racouchot syndrome (elastoidosis nodularis
      cystica et comedonica) in a male mason aged 65, associated with nodular
      ulcerative type of basocellular skin neoplasm and seboroic keratosis of the
      irritative type. A special reference is given to nodular cystic elastoidosis
      (NCE) with concurrent numerous skin changes characteristic for chronic actinic
      skin lesions which were clinically evidenced. An objective examination of the
      patient revealed the presence of multiple follicular comedones, black in colour,
      the size of a pinhead, and of yellowish follicular papulas, 2-5 mm in size, of
      solid consistency, on the top of which is a formation similar to comedone. These
      eflorescences are densely disseminated in periorbital, zygomatic and temporal
      regions of the face, sparsely on the nose, forehead and preauricularly. In other
      regions of the face and neck other manifestations of chronic actinic skin lesions
      with characteristics of "citrine skin", cutis rhomboidalis nuchae and elastoma
      Dubreuilh are present as wall. In the right nasolabial furrow a clearly edged
      tumefaction, 1.2 x 0.8 cm, which belongs to the nodular-ulcerative type of
      basocellular skin neoplasm is seen. Seboroic keratosis of the irritative type was
      observed on the skin in the middle of the upper lip was histologically verified.

PMID- 1344470
TI  - [Pneumococcal meningitis from 1974 to 1984].
AB  - We examined a group of 22 patients presented with the acute infective meningeal
      syndrome. Lumbar punction confirmed diagnosed purulent meningitis-
      meningoencephalitis, and bacteriologic liquor culture identified Streptococcus
      pneumoniae as a cause of the disease. Patients were mostly aged over 30. Clinical
      picture revealed signs of general infection and the meningeal syndrome. The
      severity of the disease was assessed on the basis of apparent signs of general
      infection, state of consciousness and endotoxic shock symptoms. Severe
      consciousness disorders were present in 16 (72.72%) patients. In our patients
      possible pneumococcus infection foci were: sinusitis, otitis media, pneumonia,
      mastoiditis and adnexitis. Lethal outcome occurred in 5 (22.72%) patients. In the
      therapy we used penicillin, chloramphenicol and ampicillin along with
      corticosteroid administration.

PMID- 1344471
TI  - [The significance of radioisotope methods in the diagnosis of liver hemangiomas].
AB  - A growing use of ultrasonography for the examination of abdominal organs has
      resulted in an easier detection of hemangioma-like focal benign changes in the
      liver. Such cases ask for further diagnosis. Apart from other methods, the
      diagnosis of hemangiomas is possible by in vivo technetium-labeled erythrocytes.
      The authors present the erythrocyte labeling technique and the scintigraphic
      method carried out in 44 patients. On the basis of the obtained results they
      conclude that scintigraphy can be successfully used for the diagnosis of
      hemangiomas, especially if the changes seen by ultrasonography are big enough for
      the scintigraphy. If they are below 20 mm only tomography (SPECT) with labeled
      erythrocytes is to be considered.

PMID- 1344472
TI  - [Ultrasonic diagnosis of transitory synovitis of the hip joint in children].
AB  - The most common cause of a limp in childhood is transitory synovitis of the hip.
      At the Paediatric Surgery Clinic in Novi Sad, in the period from 1989 to 1991, 58
      children were treated for hip transitory synovitis and the diagnosis was
      confirmed by ultrasonic finding of the exudate in the joint. The ultrasonic
      investigation of the hips was performed by using Siemens and Kretz scanners
      equipped with 5 MHz linear or sector transducers. The approach to the hip was
      frontal and the lower extremity has been in the neutral position. The distance
      between the femoral neck and the joint capsule was verified according to the
      Adam's morphometric procedure. The measured pathological values were from 7 mm to
      14 mm (normal values are from 2 mm to 4 mm). In the routine transitory synovitis
      diagnosis, real-time arthrosonography of the hip shows high sensitivity, accuracy
      and selective values compared to other diagnostic procedures.

PMID- 1344474
TI  - [The effect of transcutaneous electric nerve stimulation on pain in knee
      arthroses].
AB  - The paper deals with effects of the TENS on disappearance of pain in knee
      arthrosis. Relevant investigation covered 40 patients of both sexes, different
      occupations and various age. The group was homogeneous in respect of subjective
      feeling of pain, length of illness and clinical findings. The results that were
      obtained clearly indicate the possibility of extinguishing the pain completely or
      reducing its intensity by application of the TENS which is to be used in medical
      treatment of knee arthrosis simultaneously with common drugs and physical
      therapies.

PMID- 1344473
TI  - [Modern trends in the treatment of ulcer disease (clinical study of nizatidine
      "Galitidine")].
AB  - By an analysis of nizatidine vs ranitidine activity, the authors show a
      contemporary controlled approach to the treatment of ulcer disease. In a
      prospective, randomized, double-blind, parallel comparative, multicentric study,
      the treatment of duodenal ulcer was carried out in 120 patients with H2-receptor
      blockers, nizatidine and ranitidine. The treatment lasted one or two months with
      endoscopic control of the results. The recovery of the ulcer nische in patients
      who received nizatidine, 150 mg twice daily over a month, was achieved in 89.75%
      of the cases, while in those who at the same time received ranitidine twice daily
      ulcer was suppressed in 84.61% of the patients; in those who received Nizatidine,
      300 mg once daily it was suppressed in 88.24% of the patients. Statistically, x2
      = 2.177 with p > 0.3 which shows that there is no statistically significant
      differences between the groups although the first group shows the best results.
      Adverse effects of the drugs were not observed.

PMID- 1344475
TI  - [Skin and laboratory tests: comparison of the epicutaneous patch test with the
      TTL and LIF tests in the diagnosis of medicamentous allergic contact dermatitis].
AB  - We investigated 158 patients from 15 to 82 years of age with clinically evident
      contact dermatitis, diagnosed at the Department for Allergic Diseases
      Investigations-Clinic for Dermatovenerological Diseases, Medical Faculty in Novi
      Sad, during the period of 1 year. We performed patch-epicutaneous test,
      lymphocyte transformation test (TTL) and leukocyte migration inhibition test
      (LIF). Among the 130 (82.2%) patients suffering from contact dermatitis, with the
      positive patch tests to commercial or standard battery epicutaneous allergens, 26
      (20%) had at least one positive patch test to the medicament. In these cases
      contact allergic medicamentous dermatitis (SAMD) was proved by positive clinical
      and allergic investigations. In only one case, patch test was negative, with
      booth the TTL and LIF test positive. Among the medicaments TTL and LIF tested,
      antibiotics were the most frequent in 9 (34.61%) cases, analgetics were found in
      6 (23.08%). Professional contact allergy to medicaments has been estimated in 5
      patients (19.23%). According to the obtained results and statistic findings,
      relationships between the two variables-TTL and patch test, and LIF and patch
      test, were estimated due to the contact allergy to medicaments. Both of them were
      low and negative without statistic significance. Patch test remains to be the
      irreplaceable test with regard to CAMD.

PMID- 1344476
TI  - [Smoking--I. Smoking habits, number of cigarettes smoked].
AB  - A multiphase, oncologic, population screening was carried out in 5.555 residents
      (91% of the expected number) over 40 years of age, from three districts of the
      community of Mali Idos. The poll showed that 83.1% of males and 21.9% of females
      are familiar with smoking (ex-smokers or active smokers); 45.7% of males and
      11.6% of females are active and 37.4% of males and 10.3% of females are
      exsmokers; 314 residents--11% of males and 1.3% of females smoke more than one
      pack of cigarettes daily; some of them smoke more than 60, 80, even 100
      cigarettes daily. In two age groups (40-44, 45-49) 100% of male respondents is
      familiar with smoking; in the group over 75 years of age this percent is reduced
      to one third (21.8%). We can conclude that the distribution of smoking in this
      population differed in the middle and in the second half of the century.

PMID- 1344477
TI  - [Dry eye as a therapeutic problem].
AB  - Effects of substitution therapy was investigated in 42 patients having the dry
      eye syndrome associated with systemic diseases of connective tissues (systemic
      lupus, Sjogren's syndrome, etc). Artificial tears were applied: Liquifilm sol,
      Hydroxypropyl methylcellulose 0.3% (HPMC) and Ocutal sol. After the one-month
      application of each preparation, mean values of Schirmer's test were
      approximately identical and the differences were not statistically significant
      (4.5 +/- 3.5; 4.95 +/- 4.4; 4.01 +/- 3.6), differing slightly from mean values of
      Schirmer's test prior to the treatment (4.4 +/- 3.4; 3.9 +/- 2.5). The lacrimal
      secretion did not increase after the administration of the above therapy. The
      therapy with artificial tears resulted in the improvement of subjective
      complaints (scratching, dryness and burning sensation) in 65% of cases treated
      with Liquifilm sol, in 69% upon the administration of HMPC 0.3% and in 60% after
      the application of Ocutal sol.

PMID- 1344478
TI  - [Dr. Valdimir Jakovljevic--his contribution to the art of surgery].
AB  - In this article we present biographical data of Dr Vladimir Jakovljevic, a
      surgeon (1893-1960), and his contribution to the technical approach to cephalic
      duodenopancreatectomy: the first pancreatico-jejunostomy, and first reported in
      world's literature triple different anastomosis of the jejunum with part of the
      stomach (after a 2/3 resection of the organ), choledochus and a part of the head
      of the pancreas, done by Vladimir Jakovljevic in 1934, and published in
      "Medicinski pregled" (Medical Review) in 1935. A basic surgical teaching of Dr
      Jakovljevic school of surgery is an aspiration toward the "physiological
      surgery", a technical viability for performing the most difficult operation on
      the biliary tract, a strong surgical imagination and full information about
      contemporary knowledge on surgery.

PMID- 1344479
TI  - "Right on...".

PMID- 1344480
TI  - The effect of impression technique and multiple pours on accuracy of stone
      models.

PMID- 1344482
TI  - The geriatric treatment plan.

PMID- 1344481
TI  - Periodontal consultation service.

PMID- 1344483
TI  - Transitions.

PMID- 1344484
TI  - [The place of history in nursing knowledge].

PMID- 1344485
TI  - [The elderly person and retirement].
AB  - The present aimed at characterizing the retired old population (members of the
      retired people and pensioners Association of Ribeirao Preto, Sao Paulo) who live
      in this town. The study was carried out from 01/01/89 through 31/12/89. This
      population was composed of 38 retired and old age pensioners: 30 (78.9%) males
      and 8 (21.1%) females. It was used the method for data collecting which was the
      questionnaire with close and open questions; the used technique was the recorded
      interview. As in our country the retired benefit is inferior to be work's
      remunerations in the period of activity, the retired person is obliged to look
      for other ways of income to complement that benefit, and the medical assistance,
      where it was not expected by the population.

PMID- 1344486
TI  - [The nurse in mental health outpatient clinics].
AB  - This study emerged from the preoccupation to evaluate the learning needs of
      psychiatric nurses working in an ambulatory of Mental Health. We verified the
      type of education they had, the actions they performed and the difficulties and
      facilities they found in the development of nursing interventions. It was also
      examined whether these actions are in conformity to the ones prerecognized by the
      literature or not. The data analysis showed that the majority of the actions are
      performed by nurses in distinct manners in 6 ambulatories. We perceived, in some
      events, the "function deviation" in nursing activities of nurse and the nursing
      team.

PMID- 1344487
TI  - [The results of self-irrigation in colostomy patients who have undergone a
      process of systematic training].
AB  - The present study comprises the results of the use of self-irrigation by 40
      colostomized patients, trained by us through a process of systematized training.
      The effectiveness of the training process can be checked out considering that the
      most part of the patients have adopted it in its basic features, pointing out a
      few number of technical difficulties. As to the results of self-irrigation, as a
      method for controlling the intestinal habit, we can say that 37.50% of the
      population showed an absence of fecal leakages and 42.50%, sporadic leakages
      between the irrigations; 27.50% and 35.00%, with absence of gases in the
      intervals of time and partial use of the collecting pouch, respectively.

PMID- 1344489
TI  - [Discharge of the surgical patient within the context of the health system].
AB  - Based on the assumption that surgical patients, together with their families,
      take responsibility for their own care after being discharged from the hospital
      and that they are not duly prepared for this task, we undertook the present study
      to investigate the problems of surgical patients related to discharge and to
      determine the type of care offered to these individuals within the context of the
      health system. The study included patients submitted to elective, medium surgery
      at the University Hospital, Faculty of Medicine of Ribeirao Preto, USP, during
      the first semester of 1989. Fifty patients (42 women and 8 men) of the various
      surgical specialties were interviewed during home visits. The instrument for data
      collection consisted of three parts: the first involved social and environmental
      aspects such as housing, job, family and others, the second involved the
      relationship of the individual with the health system, his/her perceptions and
      difficulties, and the third involved the biological aspects related to the
      surgical process. The data were analyzed in a descriptive manner on the basis of
      the theoretical referencial of Lalonde, which sees health as the result of a
      dynamic process of individual integration with the environment.

PMID- 1344488
TI  - [Body temperature: the planning of nursing care in checking the temperature and
      in caring for fever and malignant hyperthermia].

PMID- 1344490
TI  - [Health promotion and disease prevention: an individual responsibility or social
      responsibility].
AB  - This article is about some theoretical assumptions that have guided health
      promotion and disease prevention strategies. Some questions are raised in
      relation to the professional's interventions that consider health promotion as an
      individual responsibility. It is suggested that the focus should be on social
      changes through the professionals' consciousness in social, political, behavioral
      and economic aspects that exert influences over the population's health. These
      ideas ought to be incorporated to the nurse-client interaction.

PMID- 1344491
TI  - [Reflections on qualitative research methods in nursing].
AB  - This essay brings considerations about quantitative and qualitative research
      methods in Nursing. It boards the quantitative and qualitative methods
      specifications, makes the distinction between method and technique, and gives
      emphasis to the episthemological pressuppositions which gives basis to the
      method.

PMID- 1344492
TI  - [The integration of teaching programs in the disciplines of obstetrical nursing
      and the administration of nursing services in maternity].

PMID- 1344493
TI  - [The role of the hospital nurse in teaching patients].
AB  - Patient teaching by hospital nurse has been recognized as a relevant form of a
      patient care throughout the history of nursing. However, there are obstacles to
      carry on this practice. On the basis of the experience reported in the
      literature, the present study analyses factors which hinder the widespread use of
      this practice.

PMID- 1344494
TI  - [The human attitude in a situation facing death].
AB  - The present paper was produced in order to help students, to deal with the death
      situation. It focus on concepts and conflicts related to terminal stage, death
      and post-death period, which demands attitudes of involvement of the professional
      in this situation, and other complementary informations about the whole issue.

PMID- 1344495
TI  - [Psychomotor skills versus intelligence and affectivity].
AB  - It is an study, based on specific Bibliography, which purpose is to divulge up
      dated knowledge capable of establishing the importance of psychomotor skills. The
      article also describes the relation between the action and mental capabilities,
      both in the phylogenesis and ontogenesis level. The notion of relationship
      between all aspects that make up the human being and the environment with which
      man interacts, confirms the new global conceptions of the modern pedagogy.

PMID- 1344496
TI  - [An approach to paternity leave].

PMID- 1344497
TI  - [The patient classification system. I. The allocation of nursing personnel].
AB  - A classification system can be an essential management tool of nursing
      administrative practice. This system should exist to provide nursing with useful
      and meaningful information for decisions about staffing allocations, monitoring
      productivity, and costing of nursing services. The purpose of this study is to
      show the importance of a patient classification system, after a review of current
      literature, in the hope that a research agenda on the topic can be established in
      Brasil.

PMID- 1344498
TI  - [The nurse experiencing the formulation of nursing conduct].

PMID- 1344499
TI  - [Developing a teaching-learning process: teaching prerequisites and methods in
      the discipline of preventive and community nursing in a nursing degree course].
AB  - This paper describes the development of a teaching-learning process (TLP) guided
      by presuppositions such as: historicity, participation and horizon. This process
      has been developed by the Community and Preventive Nursing Discipline of the
      School of Nursing of Sao Paulo University, and its objectives, methods and
      strategies are described here. It is articulated to the Assistance-Teaching
      Integration Project involving the School of Nursing and Sao Paulo Mayorality.
      This process has been a valuable experience for both teachers and students, and
      it has also enabled a real approach with the Health Unit personnel.

PMID- 1344500
TI  - [Nursing diagnoses in teaching and research].

PMID- 1344502
TI  - [Vertigo and diving].
AB  - The appearance of a vertigo during scuba-diving result from different
      pathophysiological mechanism at which oppose specific therapeutic. Whether it's
      during barotrauma or decompression accident, the vestibular reach can cause
      drowning. It is possible to make the difference between barotrauma and
      decompression accident, with the good study of the scuba-diving and the time when
      the vertigo has came. So, the therapeutic will use recompression in a multiplace
      hyperbaric chamber or only hyperbaric oxygen.

PMID- 1344501
TI  - [Labyrinth fistula in chronic otitis with cholesteatoma].
AB  - The authors studied 116 surgically treated patients with labyrinthine fistulae
      due to cholesteatoma. The fistulae were most commonly localized on the lateral
      semicircular canal (75%) and much less frequently involved only the oval window
      area (7%) and the promontory (4%). The multiple fistulae were found in 14%
      patients. The closed technique was used, while the open technique was adopted
      only when the ear was deaf preoperatively, in cases of multiple fistulae and
      associated intracranial complications. The cholesteatoma matrix was not removed
      from the fistula of the oval window area or the promontory or in the cases of
      multiple fistulae and large fistulae of the lateral semicircular canal if the
      cholesteatoma matrix had penetrated into the labyrinth. The fistulae on the
      lateral semicircular canal were covered by a piece of fascia. Postoperatively
      deafness occurred only very exceptionally.

PMID- 1344503
TI  - [Current data on barotraumatic ear disease with isolated vestibular expression
      during apnea diving].
AB  - The authors have taken an interest in isolated vertiginous symptoms observed from
      free diving patients. In order to achieve a current bibliographic synthesis, they
      resume, on basis of 6 cases, the basic principles of the physics theories and the
      etiopathogenic mechanisms. They try so to help in the understanding of the
      vestibular clinical signs observed in this successful sport.

PMID- 1344504
TI  - [Subglosso-epiglottectomy: carcinologic and functional results].
AB  - The authors report on 26 cases of patients treated by subglosso-epiglottectomy
      from 1978 to 1989. Whilst as far as survival and local oncological control are
      concerned the results are encouraging, the functional results are disappointing.

PMID- 1344505
TI  - [Contralateral ear in cholesteatoma].
AB  - The authors examine 224 contralateral files of patients suffering from
      cholesteatoma. They record that the systematic study of the opposite ear can
      prove to be of interest, given the numerous anomalies found. One ear in two has a
      contralateral pathology. In 32% of the cases, there is a retraction pocket, and
      in 14% a cholesteatoma. The mean time for a cholesteatoma to appear from a
      retraction pocket varies by 24 months in 44% of the cases, thus demonstrating the
      necessity of examining the opposite ear, as a dynamic evolution exists. Of these
      pockets, 2% in fact evolved, these statistics, to a true cholesteatoma.

PMID- 1344506
TI  - [Morphofunctional correlations in children with upper maxillary endognathia].
AB  - In this study 23 oral breathing children suffering from maxillary hypoplasia
      (endognathia associated with skeletal class II or III), selected for rapid
      maxillary expansion (RME) have been investigated by active anterior rhinometry.
      None of these patients presented O.R.L. pathologies during clinical examination
      except for some sporadic cases of adenoid hypertrophy (5 cases). Rhinomanometric
      and cephalometric examinations carried out before and after RME treatment showed
      a good correlation between the nasal respiratory function parameters and the
      structural cephalometric elements investigated by means of teleradiography. In
      particular, an important reduction in nasal respiratory resistance in all
      patients with conversion from oral to nasal respiration in the majority of cases
      corresponds, together with cross-bite resolution, to increased transversal
      dimension of the maxilla produced by RME. A clear regression in adenoid
      hypertrophy, where present, is also noted without any type of O.R.L. treatment.
      The improved respiratory situation could therefore produce benefits on the
      trophism of the nasal mucous and the lymphatic rhinopharyngeal tissue. Agreement
      between clinical, radiological and rhinomanometric findings confirm the
      usefulness of this method in diagnosing and following-up patients with this
      problem.

PMID- 1344507
TI  - [Congenital cholesteatoma of the middle ear and mastoid. Apropos of 5 cases].
AB  - Five cases of congenital cholesteatoma of the middle ear and mastoid as defined
      by Derlacki's criteria were encountered over a 14 month period. They make up 5%
      of all cases of cholesteatoma managed over the same period of time. Three were
      young children and all presented with unilateral hearing loss. One had associated
      multiple congenital abnormalities of the external and middle ear. Only in one
      patient was the diagnosis made on initial otoscopic examination and the remainder
      diagnosed on CTscan, myringotomy and tympanotomy. All were operated on; three by
      the intact canal wall technique, one by the canal down technique with mastoid
      cavity obliteration and one by atticotomy with lateral attic wall reconstruction.
      One patient required a second stage operation for excision of an extension of
      disease deep to the superior semicircular canal via the middle cranial fossa
      approach in order to preserve cochlear function. These five cases illustrate the
      diagnostic pitfalls of this condition in which silent danger lurks behind an
      intact tympanic membrane.

PMID- 1344508
TI  - [Arachnoid cysts of the cerebellopontine angle].
AB  - The authors report two cases of arachnoid cysts of the cerebello-pontine angle.
      The otologic symptoms were unsteadiness, hearing fall and tinnitus. In the first
      case, the patient who presented a cerebellar syndrome was operated. Afterwards
      the hearing felt and he developed a transient hydrocephalus. The symptoms
      disappeared in 9 months. In the second cas, the patient was not operated. She was
      treated medically and supervised. Then the symptoms disappeared too. The authors
      review the paraclinic exams especially MR, relevant to the diagnosis and discuss
      the opportunity of a surgical operation.

PMID- 1344509
TI  - [Primary meningioma of the geniculate ganglion: apropos of a case].
AB  - Based on a clinical observation and a literature review, etiologic hypothesis,
      clinical, radiological and therapeutics characteristics of intratympanic
      primitive meningioma are described. Those tumors arise from arachnoid cells, some
      may be carried along the nerve sheath within the Fallopian canal during
      embryology.

PMID- 1344510
TI  - [Ankyloglossum superius: apropos of a case].
AB  - The authors report a rare observation of ankyloglossum superius i.e. the
      attachment of the tip of the tongue to the anterior part of the palate, with an
      ectrodactyl of the fingers and toes. Following a review of the literature, this
      provide an opportunity to recall this pathology, the physiopathogenesis of which
      remains unknown falling within syndromes of malformation affecting both the
      mouth, face and limb, namely orofacio-digital syndromes and syndromes of
      hypogenesis of the mouth, jaw and limbs.

PMID- 1344511
TI  - [Congenital laryngeal atresia: apropos of a case].
AB  - A case of congenital laryngeal atresia in which the laryngeal lumen was
      obstructed by a soft, smooth protrusion is reported. Laryngeal stenosis was
      located at the glottic level and appeared as a protrusion reducing the laryngeal
      lumen to a few millimeters. The stenotic tissue consisted of striated muscle
      fibres cross-linked through their midlines.

PMID- 1344512
TI  - [Spontaneous hematoma of the thyroid gland: apropos of 2 cases].
AB  - Authors report two cases of spontaneous hematoma of the thyroid gland. Emergency
      surgery was performed on note of them. After reminding the role of different
      investigations, they discuss the interest of computed tomography to exclude
      extracranial carotid artery aneurysm. They explain a therapeutic approach
      according to the repercussions of hematoma: a compressive syndrome requires a
      difficult emergency surgery.

PMID- 1344513
TI  - [Multistaged cryopreservation of tympano-ossicular grafts. I. Preservation
      procedures].
AB  - Good conservation of tympano-ossicular grafts is still actual. Theoretical
      principles of cryobiological action and the detailed description of applied
      method are given. Newly developed multistaged cryoprocedure in liquid nitrogen AT
      196 degrees C with 9% DMSO showed well the microscopic appearance of connective
      tissue transplants without alterations of metabolical and mineral content. The
      conservation was mainly successful in peripheral, perivascular and perihaversian
      regions, while central zones gave signs of hypothermic lesion.

PMID- 1344514
TI  - [Congenital cholesteatoma of the middle ear in children].
AB  - In a series of 16 middle ear cholesteatomas of a congenital type are reported in
      children; the youngest (18 months) presented with a bilateral case. Whereas a
      simple tympanoplasty could cure a localized pearl, typically anterosuperior in
      the mesotympanum, the stapes is fast eroded (7 cases) if progression goes on.
      Intact canal wall technique in 2 stages was the typical procedure. Good hearing
      results were generally achieved (except in one case of fixed footplate): 9
      cases/14 with an ABG within 20 dB and an AC level within 30 dB.

PMID- 1344515
TI  - [Multistaged cryopreservation of tympano-ossicular grafts. II. Transplantation
      procedures].
AB  - Tympano-ossicular transplants conserved by multistaged cryopreservation in liquid
      nitrogen on AT -196 degrees C were transplanted ortho and heterotopically in
      rats. This experimental histological investigation showed well the
      biofunctionality and biocompatibility (preservation of osteoneogenetically potent
      cells, signs of reorganization and decreased transplantative reactions on such
      grafts). Thus adequate preservation of tissues by means of this procedure was
      proven.

PMID- 1344516
TI  - [Surgical rehabilitation of deglutition after partial surgery of the pharyngo
      larynx].
AB  - The authors report four cases of severe deglutition disorders after partial
      laryngectomy. Three had collagen injection and one had a plastic reconstruction.
      They propose to use dynamic imagery in order to have a better selection of the
      patients.

PMID- 1344517
TI  - [Tumors of the parotid area. Apropos of 203 surgical explorations].
AB  - The authors present their clinical, radiological and histological conclusions,
      according to a retrospective personal study about 203 chirurgical explorations
      from the parotid gland. The pleomorphic adenoma and the cystadenoma are presented
      more precisely and basically their chirurgical indications; the other
      histological types met are only presented through several tables.

PMID- 1344518
TI  - [Bilateral chylothorax after radical neck dissection. Apropos of a case].
AB  - Bilateral chylothorax following radical neck dissection is an uncommon
      complication of head and neck surgery. Only 9 more cases have been reported in
      the English literature until now. Early recognition is not difficult if it is
      bear in mind when evaluating dyspnoeic patients with bilateral pleural effusions
      after neck dissection. In this paper the authors report their experiences with a
      case and comment on the treatment employed. The authors believe that due to its
      potential severity, it must be considered when ever head and neck surgery is
      performed.

PMID- 1344519
TI  - [Leiomyosarcoma of the larynx: presentation of a case].
AB  - The authors report a new case of laryngeal leiomyosarcoma. The patient was a 43
      year-old-man. The tumor extended to the left vocal cord, the paraglottic space
      and the deep layers of the left false vocal cord. Histologically, the lesion
      showed the typical pattern of a grade-3 leiomyosarcoma. Immunochemical studies
      revealed a strong positive staining with the actin smooth muscle antisera. A
      partial laryngectomy was performed. There was no evidence of recurrent or
      metastatic disease 10 months after surgery.

PMID- 1344520
TI  - [Results of audiometric and vestibular tests in Cogan syndrome: apropos of a
      case].
AB  - The authors report on a case of Cogan's syndrome pointing out that hearing loss
      is due both to cochlear lesions from likely immunitary origin as well as to
      widespread alterations of auditory central nervous structures. This
      interpretation allows to explain the apparent discrepancy of the found clinical
      and instrumental data. From a therapeutic point of view, the authors assert the
      necessity of an early corticosteroid therapy to obtain some appreciable result.
      Anyway, they point out how prognosis for auditory function in Cogan's syndrome is
      often very poor.

PMID- 1344521
TI  - [Our experience with percutaneous endoscopic gastrostomy in pharyngo-laryngeal
      surgery].
AB  - Percutaneous endoscopic gastrostomy (PEG), is an enteral feeding procedure, easy
      to tolerate and simple to perform. PEG appears to be an alternative to surgical
      gastrostomy. Used in ten patients with E.N.T. cancer, we only observe two minor
      complications. Advisable in a first time for the feeding of patients with
      palliative treatment, we propose PEG for patients in position to have a long and
      difficult rehabilitation of swallowing.

PMID- 1344522
TI  - [Deafness, induced by sodium ethacrynate in guinea pigs, alleviated by microwave
      treatment].
AB  - Microwave is used to treat temporal hearing loss caused by intravenous injection
      of the ethacrynic acid in guinea pigs. The recovery of hearing is much faster in
      the treated groups than in the control group. The article proposes possible
      mechanism of the effects against the ethacrynic acid induced deafness and assume
      that the result of this research can provide an experimental basis for treatment
      of some perceptive deafness due to ischemia of stria vascularis of the cochlea.

PMID- 1344523
TI  - [Comparison of 2 materials in the reconstruction of the tympanic membrane. Our
      experience in 300 patients].
AB  - The authors evaluated the results obtained from the tympanic membrane
      reconstruction in 300 patients affected by simple, purulent or cholesteatomatous
      chronic middle ear otitis. In this tympanic membrane reconstruction they used:
      jugular vein strip of a calf and temporal muscle fascia in 150 cases. On
      pathological basis (simple, purulent and cholesteatomatous otitis) they used the
      overlay or the underlay method. In 5 years that follows, the materials (vein and
      fascia), if properly used, would give similar results. For such reasons the
      authors proposed: temporal muscle fascia autotransplantation with underlay method
      in partial myringoplasty; heterotransplantation of modelled jugular vein strip
      with overlay method in subtotal or total myringoplasty.

PMID- 1344524
TI  - [Apropos of the infratemporal pre-auricular approach (its value in the approach
      to the midline skull base].
AB  - The role of the infratemporal pre-auricular pathway to the median base of the
      skull resides in the fact that it enables very wide access to this region while
      sparing the facial and auditory nerves. Among the operations performed on the
      approaches of the base of the skull by their teams, the authors chose a
      particularly typical observation dealing with the indication of this pathway: a
      34-year old male with a giant cholesteatoma of the tip of the petrous bone
      totally surrounding the internal carotid artery along its entire (intrapetrous)
      length, from the cervical region to the cavernous sinus, having invaded the
      clivus and pushed back the brainstem. This lesion is located on the side of the
      only healthy ear. The patient is completely deaf in the ear on the other side.
      The operation enabled its complete exeresis while respecting the facial, auditive
      and vestibular functions.

PMID- 1344525
TI  - [Secondary rhinoplasties: failures at the bone stage].
AB  - Based on a personal experience, the author exposes the problems and describes the
      failures who can occur during and after the "bony stage" of the rhinoplasty. The
      surgical treatment will be exposed. Successively: correction of the dorsum
      (resection of the bony hump) with incorrect nasofrontal angle, residual hump,
      "saddle nose"; lateral osteotomy and bony step; transversal and paramedian
      osteotomy with possibility of "open roof" so as residual deviation.

PMID- 1344526
TI  - [Acute vertigo caused by cerebellar vascular accident].
AB  - At the beginning, small cerebellar strokes may present only with acute onset of
      vertigo, unsteadiness and unidirectional nystagmus, like a vestibular neuritis.
      In some cases, it is associated with tinnitus and hearing disturbance, like an
      endolymphatic hydrops. Other cases may mimic a benign cupulolithiasis, with only
      a paroxysmal positioning vertigo. Attention should be focused on transient
      associated symptoms: headache and blurred vision. One should not wait for
      classical cerebellar clinical signs: they are subtle and they appear late. Within
      a few days, the clinical picture will change: vertigo will disappear, while
      unsteadiness will progress. The electronystagmography confirms the integrity of
      the vestibular peripheric system. The cerebral CT Scan will show the ischaemic
      lesions only several days after the onset of the symptoms. A magnetic resonance
      imaging is far more efficient. Small cerebellar strokes have a good prognosis:
      complete recovery may be hoped with acetylsalicylic acid treatment and
      kinesitherapy.

PMID- 1344527
TI  - [Predictive value of high frequency audiometry in otosclerosis].
AB  - A study was carried out to evaluate the value of high-frequency audiometry in
      stapes surgery in cases of otosclerosis. The hearing function was measured pre-
      and postoperatively by means of conventional and high-frequency audiometry
      (Demlar 20k). The operative findings of the gradation of otosclerosis were
      compared with the pre and postoperative audiometrical measurements. The results
      of this study point out that a clear relation exists between the preoperative
      high tone audiogram and the gradation of otosclerosis. In conclusion, we state
      that high-frequency audiometry can predict the state of stapes fixation in
      otosclerosis and that can be important in stapes surgery.

PMID- 1344528
TI  - [Malignant cervical epithelial adenopathy from unknown primary source. Apropos of
      a series of 54 cases].
AB  - Fifty four patients with cervical lymph node metastasis from an unknown primary
      tumor underwent treatment from 1969 to 1988. Fourty five underwent radical neck
      dissection. 69% had node capsular effraction and 36% perinodal vascular embolism.
      Thirty four patients underwent postoperative radiotherapy including rhinopharynx,
      cervical oesophagus and all the bilateral cervical nodes. The primary tumor
      appeared after treatment in 7 cases. Total survival rate is 36% 5 years after
      treatment. Vascular embolism aggravates the prognosis. Radiosurgical association
      allow effective control of loco-regional cancer but does not improve survival
      rate. Prognosis is aggravated by metastases arising (18%).

PMID- 1344529
TI  - [Repair of the auricular area after petrosectomy].
AB  - The authors report a retrospective series of 12 patients presenting periauricular
      tumors having invaded the external auditory canal and concha: 5 squamous cell
      carcinomas, 3 basal cell carcinomas, 2 Darrier-Ferrand sarcomas, 1 parotidean
      adenocarcinoma, 1 radionecrosis. The operation included an extralabyrinthic
      petrosectomy, an amputation of the pavilion, and a ganglionic evidement following
      a histological analysis. The reconstruction processes used 3 pedicle grafts and 9
      free grafts. The carcinological extension modalities of the cancers invading the
      entire external auditory canal require the sacrifice of the tympanic cavity and
      an external temporalectomy in a single block for carcinological and functional
      reasons. The massive invasion of the concha inevitably leads to the sacrifice of
      the auricular pavilion. The best means of reconstruction is with the free graft
      of the musculus latissimus dorsi. The price to be pay esthetically must be
      reduced by the placement of an epithesis.

PMID- 1344530
TI  - [RNA extraction, in vitro translation and two-dimensional analysis of
      oncoproteins in cancers of the upper respiratory and digestive tracts].
AB  - After a review of the literature concerning oncogenes expression of in head and
      neck carcinomas, the authors studied RAN extraction, in vitro transduction and
      two dimensional analysis of oncoproteins in head and neck carcinomas. The results
      between the tumoral tissue and normal tissue were compared significantly more
      oncoproteins spots were found in the tumoral tissue analysis.

PMID- 1344531
TI  - [Comparative contribution of endoscopy, x-ray computed tomography and MRI in the
      preoperative evaluation of cancers of the endolarynx: apropos of 18 surgically
      treated patients].
AB  - The authors carried out a prospective and comparative study of 18 patients with
      endolaryngeal carcinoma, with preoperative imaging of the extent of the disease
      by computed tomography (CT) and magnetic resonance imaging (MRI). The
      correlations between CT, MRI, endoscopy and postoperative histology are reported.
      It appears to the authors that the contribution of imaging is evident and that at
      present the reliability of CT is comparable to that of MRI, taking account of the
      current technical problems of MRI.

PMID- 1344532
TI  - [Melanoma of the ORL mucosa].
AB  - The study of ENT mucous melanomas (ENT MM) was performed retrospectively, based
      on 20 patients treated in Bordeaux and 156 detailed files taken from the
      international literature. Each paragraph is followed by a review of the general
      literature. The ENT MM, a rare form of melanomas, presents a majority of nasal
      locations. The mean age is 63 years old. The sex ratio trend is towards one. The
      aspecific call signs partially explain the delayed diagnosis. The difficult
      pathological examination is assisted by tumoral markers. Mean survival is two and
      a half years without any clear prognostic factors as for cutaneous melanomas.
      Treatment is essentially surgical, but adjuvant radiotherapy may have a
      significant effect. The other treatments are palliative.

PMID- 1344533
TI  - [Olfactory esthesioneuroma. Apropos of 12 cases].
AB  - The authors report a 12-case series of olfactory esthesioneuromas, in which they
      review the main characteristics of this rare tumor. The olfactory esthesioneuroma
      diagnosis should be evoked for all nasal tumors, especially for tumors
      originating in a high position. This diagnosis is confirmed by the difficult
      pathological examination, which currently benefits widely from immunohistochimy.
      Prognosis is poor and surgery is the main treatment, associated with varying
      degrees of radiotherapy. As far as chemotherapy is concerned, its role must be
      clarified.

PMID- 1344534
TI  - [Indications and results apropos of 290 endonasal ethmoidectomies].
AB  - An intranasal ethmoidectomy prospective study was carried out from 1985 to 1991
      on 152 patients and 290 ethmoidectomies. This surgery is intended for patients
      who have been treated often for nasal polyps, chronic ethmoiditis and recurrent
      sinus barotrauma. A discrepancy was observed between patients satisfaction (82%)
      and clinical symptoms, given that results remain good in 75% of the cases three
      years afterwards but only in 60 cases after five years. There is a recurrence of
      nasal polyps in 36% of the cases.

PMID- 1344535
TI  - [Maxillary Aspergillus sinusitis. Comments apropos of 20 cases].
AB  - About a series of 20 aspergillus maxillary sinusitis, the correlation between
      this pathology and previous dental treatments is emphasized. In some cases such
      as sinusitis can occur without any dental pathology and/or in absence of foreign
      body on the X-rays. C.T. findings are the basis of the diagnosis. Surgical
      treatment, using endonasal micro surgery, has been performed in all cases.

PMID- 1344536
TI  - [AIDS and lymphoma of the ear].
AB  - The authors describe the circumstances for detection of an AIDS lymphomatous
      complication revealed by an otological picture in one patient. The lymphomatous
      pathology not related to HIV is reviewed. The particularity of these lymphomas,
      when they are related to HIV, is their frequent initial extra-ganglionic
      location, their high grade histological type and their poor prognosis. The
      authors emphasize the need to perform a biopsy rapidly when confronted with any
      external otitis resistant to general and local treatments.

PMID- 1344537
TI  - [Cyst of the thyroglossal tract with localization at the base of the tongue].

PMID- 1344538
TI  - [Laryngeal sarcoidosis: apropos of a case].
AB  - The authors report an unusual case of laryngeal sarcoidosis. After having
      explained it, they describe the elements of diagnosis about this rarely isolated
      pathology, its complications and treatment as well.

PMID- 1344539
TI  - [Thyroid teratoma in adults].
AB  - A new case of thyroid teratoma is reported in an adult and the heighten other
      cases of the literature are reviewed. This pathology, rather frequent and always
      benign in infants, is distinguished in adults by a malignant metastatic course
      for 14 cases of 19. The reported case, the second one in a male adult, remains a
      benign one after 14 years.

PMID- 1344540
TI  - [True osteoma of the maxilla. Apropos of 3 cases].
AB  - The authors report 3 cases of authentic maxillary osteoma. Two cases concerns an
      exceptional osteoma with multiple localisation and the third case a giant maxilla
      osteoma. Topographic, diagnostic and therapeutic notions of these tumors are
      related.

PMID- 1344541
TI  - ["Conservative" transmandibular buccopharyngectomy].
AB  - Tumors of the amygdaline region were up until now most often treated by
      transmandibular buccopharyngectomy (TMBP) with a systematic sacrifice of the
      mandibular angle. This exercise justified by wide carcinological imperatives, a
      larger surgical facility and simple immediate postoperative follow-up, in fact
      systematically shows a substantial esthetic and functional prejudice. This
      principle was reinforced by the occurrence of osteitis during the first attempts
      of osseous reconstruction using steel wires opposite the mandibular angle
      (Dargent, Charachon, 1963). In 1989, Gehanno and Beauvillain published a
      mandibular conservation technique by vertical paramedian osteotomy, right in
      front of the mental nerve, shifted from the future field of radiation, with
      osteosynthesis by titanium plates. This technique appeals to us because it is
      easy to use, reliable and carcinologically safe. We have currently adopted it
      with satisfaction for 8 of our patients over an 18-month period, without any case
      of osteitis and with both good esthetic and functional results.

PMID- 1344542
TI  - [Tobacco and cancer of the larynx: a prospective survey of 58 patients].
AB  - A prospective investigation about the influence of the tabagism and its
      characters on the laryngeal cancer has been led in the department of oncology in
      the Hospital Center Ibnou Rochd in Casablanca from December 1990 to June 1991.
      The investigation concerned 58 new patients. We conclude from this investigation
      that the risk of cancer increases with the intensity of the tabagism (the
      precocious age at the beginning, long duration, high number of packets/years;
      black tobacco, deep inhalation of the smoke, absence of weanling). The risk
      increases with the association with an intense alcoholism. We don't find the
      professional exposition. These cancers related to tobacco have epidermoid
      predominance. Finally, the major interest of this study is to convince us about
      the ampleness of this flail and to lead us through an educative action for the
      preventive fight against tobacco because of the risk of laryngeal cancer.

PMID- 1344543
TI  - [Laryngeal and tracheal complications of prolonged intubation].
AB  - Based on a retrospective study of 595 patients having undergone prolonged
      intubation, the authors present the main complications encountered and, in
      particular, the mucous ulceration which appears to be systematic and is itself at
      the origin of secondary stenosizing or granulomatous sequelae. Research is still
      needed concerning the follow-up of the intubated patients in order to limit the
      pressures exerted between the cordal mucosa or the tracheal mucosa in contact
      with the endotracheal tube. A systematic check upon removal of the tube decreases
      the secondary sequelae by starting adapted antacid, anti-inflammatory and
      antibiotic treatments, as well as certain acts of laryngeal microsurgery and, in
      some cases, laryngeal rehabilitation for both the voice and deglutition.

PMID- 1344544
TI  - [Stuttering: what does it tell us (body and speech)? What can be proposed (body
      and psyche)?].
AB  - The language can not be broken away from the oral: the actual psychoanalytic
      conceptions are called again. That allows to approach the stammering in its
      clinical theoretic aspects. One can consider the relation to the mother, the
      accession to the spoken word, the voice's wealth and possibilities, the necessity
      of the listening and of silence, with in all its aspects the emergence of the
      differences in stammerer subject or not. The links with the body and/or with the
      corporeal bring the notions on the psyche or psychic reality and permit to
      understand better the importance of a therapeutic activity (sufficient or with
      other treatments) the relaxation: its effects are multiples and I can give to the
      spoken word more spoken word.

PMID- 1344545
TI  - [Some considerations on stuttering].
AB  - Stuttering implements communication with interference through challenges other
      than sharing information, messages and emotion. This dramatic behaviour implies a
      phobic origin. The therapist must reproduce the symptom in its overall economy.
      Attentive listening, reassurance and non-submission of the esteem to the
      performance of expression should lead to a veritable reassessment of the
      challenges of expression.

PMID- 1344546
TI  - [Parkinson disease and communication].
AB  - Communication abilities imply multifactorial analysis. These disorders in
      Parkinson's disease involve speech, graphism, functional and paraverbal gestures.
      The patient's isolation in a major form of disease is dramatic. Functional study
      requires an analysis of each factor; progress should be realized for an objective
      approach. With a therapeutic objective in view, the most impaired features, and
      the patients real situation and way of life must be evaluated. Some training
      measures are useful especially for social adjustment and motivational
      reinforcement.

PMID- 1344547
TI  - [Vocal dysfunctions: bases for rehabilitation].
AB  - Based on our observations of vocal dysfunction modes, we set up a classification
      of dysfunctions. Most often, we encounter a "prolonged and usual vocal forcing on
      an anatomically normal larynx". This forcing often essentially predominates
      breathing, but it may predominate the larynx, in the posterior glottis or on the
      vibrating area of the vocal cords. We individualized the very specific group of
      dysphonias with limited tone where the forcing in located, especially in the
      resonators. We reviewed the dysphonias with modified larynx, by secondary lesions
      or primitive pathologies. Analysis of the vocal dysfunction mode makes it
      possible to establish a therapeutic programme adapted to each case with a
      functional aim.

PMID- 1344548
TI  - [Phoniatric and orthophonic management of patients during the awakening phase of
      coma].
AB  - The creation of a structure adapted to serious head injuries, in the awakening
      phase of a coma, enables early treatment of these patients upon leaving intensive
      care. Along with a pluridisciplinary team, speech therapists will help establish
      non-verbal communication by setting up a yes-no code and by favouring and
      programming the resumption of deglutition before soliciting verbal communication
      and recuperation of the memory and all the cognitive functions.

PMID- 1344550
TI  - [Phoniatric aspects of reconstructive laryngectomy].
AB  - Reconstructive laryngectomy has been performed at the E.N.T. Clinic in Ferrara
      for some time. After surgery the patients undergo speech therapy and phoniatric
      treatment for a period of time varying from 2 to 6 months. In order to better
      evaluate the vocal quality obtained after such reeducation the vocal emissions of
      25 patients were examined and recorded. The recorded material, made up of
      prolonged vowels and 6 phonetically balanced sentences, was then evaluated by a
      panel of 7 "trained" listeners. The evaluation score-card proposed by Woiers in
      1977 was used in taking the data. This not only provides a scale for evaluating
      the main voice quality features, but also includes a final judgement on
      parameters including intelligibility, acceptability and pleasantness. Statistical
      processing of the data inherent to voice quality indicated a decrease in
      intensity and pitch when compared to normal values. Nonetheless, the listening
      test showed a high degree of intelligibility, acceptability and pleasantness.
      These values confirm the fact that, although the new voice achieved through
      reconstructive laryngectomy surgery is less sonorous, it allows for perfectly
      understandable, socially acceptable speech.

PMID- 1344549
TI  - [How to evaluate velar insufficiency?].
AB  - The evaluation of velar insufficiency is absolutely necessary in order to assess
      the results of surgery of the labial palatal cleft. In addition to the clinical
      examination which remains indispensable, the aerophonometer, applicable to adults
      and children as from the age of 3, enables simultaneous measurement of the flow
      of buccal air, the flow of nasal air, and the buccal phonogram. The comparison of
      the lines, the relation of the nasal air and buccal air flows, upon the emission
      of two standard sentences with and without nasal components, enables an objective
      assessment of velar functioning.

PMID- 1344551
TI  - [Crico-arytenoid articulation and reconstructive laryngectomy].
AB  - The crico-arytenoid articulation is a functional, anatomical entity the
      preservation or damage of which plays an important role in laryngeal
      carcinological surgery. In reconstructive laryngectomies, particular biomechanics
      of the neoglottis were observed at the origin of a specific rehabilitative
      protocol as well as an evolution over time of this crico-arytenoid unit.
      Functional readaptation should simultaneously deal with breathing, swallowing and
      speech. From D1 to D7, breathing work is started. From D6 to D14, swallowing is
      begun by establishing the sphincter. From D3 to D120, phonation work is dealt
      with by establishing a sphincter and the vibrator.

PMID- 1344552
TI  - [Etiology of specific types of dysphasia and dyslexia as well as their natural
      supporting mechanism (theoretical approach and therapeutic response)].
AB  - The respective role of the organic and psychological factors is discussed. The
      importance of the individual's reaction to his own disorder is emphasized. This
      reaction according to the author promotes an evolution from a simple delay to a
      specific deviation. It is this reaction that the program "Natural Accompaniment"
      aims to contain or to defuse in proposing re-educative technics relying upon two
      principles: demands requiring no effort, priority to the words' significance.

PMID- 1344553
TI  - [Vocal audiometry: the "phonatome" recognition test. Principle, technique,
      initial results].
AB  - Whereas tonal audiometry makes it possible to analyze the elementary deficits of
      hearing, vocal audiometry enables an overall synthetic assessment of these
      deficits. The vocal material usually used is composed of lists of sentences,
      words, logatomes or even phonemes. The authors suggest resorting to lists of
      phonetically balanced phonatomes or diphonemes. Among the advantages this
      technique offers, are the rapidity of the test, the excellent representativity of
      the most informative acoustic components of speech and the elimination of the
      extralinguistic factors of speech recognition.

PMID- 1344554
TI  - [Acoustic and mechanical interpretation of the "on-off" effect].
AB  - The on-off effect is a particular form of the stapedial reflex. It is presented
      as a double positive deflection appearing when the stimulus starts and stops.
      This type of reflex is very frequent in beginning otospongiosis. The mixed theory
      assimilates the annual ligament of the stirrup to an elastic pin which obeys the
      physical laws of a spring. Otospongiosis produces a shortened sement and
      thickening of the annular ligament, with an increase in its rigidity, responsible
      for deafness of the low sounds at the beginning of the disease. The acoustic and
      mechanical theory enables a clear explanation of the lines supplied by the
      different types of instruments (220 Hz or 600 Hz). It also specifies the role of
      the annular ligament in various hearing pathologies.

PMID- 1344555
TI  - [Use of standard protocols in the evaluation of voice disorders].
AB  - The purpose of this paper is to present a protocol for the use of standard forms
      in the evaluation of laryngeal structure and function in patients with voice
      disorders. The forms are designed to cover all the essential parameters needed to
      reach an accurate descriptive diagnosis which allows us to have an appropriate
      therapy plan according to the individual's detailed observations. It also gives
      us a consistent standardized evaluation form to measure changes after therapy
      whether behavioral, medical or surgical, and to compare different observations
      across patients. Reporting observations in this consistent manner will make
      characteristic patterns of different vocal behaviors readily obvious to the
      researcher or the clinician and reduce the possibility of missing any important
      details. The protocols are: indirect laryngoscopy, video-stroboscopic-evaluation
      form, functional voice and auditory perceptual voice evaluation.

PMID- 1344556
TI  - The evaluation of the changes of voice registers in trainee singers by using the
      two-channel signal processing method.
AB  - This study was done at the ENT Department of the Ege University Medical Faculty
      on twenty trainee singers. Using the two-channel signal processing method, the
      electroglottographic (EGG) signals and the voice signals were digitized with an
      analog-digital converting card during an ascending and descending glissando
      exercised by the trainee singer. These signals were recorded on the computer's
      hard disk and the obtained data was analysed. It has been determined that the EGG
      signals were more irregular the singing formant of the voice signal was very weak
      or absent and the change of register was more significant in less trained
      singers. This method can be used to evaluate objectively the change of voice
      registers in the training of the singers and be easily performed by adding an
      analog-digital converting card to a PC computer, without the need of expensive
      modern devices.

PMID- 1344557
TI  - [Pharyngeal video-fibroscopy: value in the management of apneic snoring].
AB  - The pharyngeal video fibroscopy (P.V.F.) should complete the classical
      diagnostical management of each snoring associated with obstructive sleep apnea.
      Easily made on a seated awake patient the P.V.F. is the one dynamical pharyngeal
      procedure. It also let see the snoring and reproduce the upper airway
      obstruction. The Muller test seats the level of this obstruction, helps the
      surgeon in the choice of the procedure and should reduce the failure rate.

PMID- 1344558
TI  - [Hearing aids and AIDS: apropos of a case].
AB  - Aids carriers must be fitted with hearing aids early due to their life
      expectancy. Hearing aids of which the electro-acoustic specificities make it
      possible to lessen the successive aggravations must be foreseen.

PMID- 1344559
TI  - [Deviations of the nasal septum and their relation to tubal physiopathology].
AB  - It is frequently shown by the specialist, the relation exists between an
      obstructive septal deviation and the bad function of the Eustachian tube. Nasal
      physiopathology, as regulator of the tubaric function has been established as a
      controversial subject during the past two decades. This research demonstrates the
      relation between the septal deviation and tubaric pathology.

PMID- 1344560
TI  - Transtympanic ventilator tubes in the treatment of seromucous otitis. Indications
      and results.
AB  - 400 patients with bilateral secretory otitis media (SOM) were treated with
      ventilating tubes (VT) in a prospectiv study. The ear drums were normal on both
      sides before VTs treatment thus allowing ear drum changes and complications
      during VT treatment to be recorded. 618 VT were placed in the ear drum after
      suction of the fluid. In 182 patients unilateral myringotomy with suction of
      fluid were done and VT placed in the contralateral ear. Adenoidectomy with
      myringotomy, with an obstructing adenoid, gave 30% better chance. 10 different
      VTs were used. The most frequent pathology found in the ear drum after one period
      of VT treatment was tympanosclerosis. In the ears only treated with myringotomy
      tympanosclerosis occurred in 1%. 3 factors seemed to give more tympanosclerosis:
      metal (stainless steel or titanium), polyethylene and prolonged stay-time in the
      ear drum. Chronic perforations of the ear drum occurred with great variations
      between the different tubes. The Goode modified T-tube caused perforations in
      17%. In the other VTs the perforations occurred in 2.1%. Chronic perforation
      together with tympanosclerosis will happen more often when the VT is made of
      polyethylene compared to silicone or fluoroplastic (p < 05). 90% of the
      perforations were located at the site of the VT. The ideal VT will stay in for 8
      18 months at an average and it can be shown to improve middle ear function better
      than only waiting or myringotomy. Long-term VTs should not be used at the first
      VT procedures.

PMID- 1344561
TI  - Stapedectomy versus stapedotomy: a comparison.
AB  - Two hundred and fifty consecutively operated stapes procedures operated by the
      author for otosclerosis are presented. A fat-wire stapedectomy prostheses
      (Schuknecht) was used in 152 cases and a Fisch teflon-wire piston was used in 98
      ears. Of the 250 procedures 33 patients had bilateral surgery. The operations
      were done in local anaesthesia in most cases and with endomeatal incision. The
      fat-wire prostheses gave in 95% a closure within 10 dB and the rest 5% closed
      within 11-20 dB. The Fisch teflon-wire piston gave a closure within 10 dB in 87%,
      within 11-20 dB in 12% and within 21-30 dB in 1%. The speech reception was better
      after operation in 97% of patients operated with the fat-wire prostheses and in
      99% of patients having the teflon-wire piston. It was a significant difference at
      20 dB level of speech improvement (p < 02) in favour of the teflon-wire piston.
      The surgery for otosclerosis is a special procedure seeking refinements in
      surgical techniques to increase safety and maintain acceptable results. Our
      results show that the small fenestra technique with 4 mm piston will give better
      speech reception and better hearing in the high frequencies. To achieve a high
      standard the operations for otosclerosis should probably be centralised to let
      the surgeon do a minimum of 8 to 10 procedures every year.

PMID- 1344562
TI  - [Somatosensory evoked potentials in peripheral diseases of the facial nerve: a
      new investigation method].
AB  - In 1988, at the Facial Nerve Congress in Rio de Janeiro, results of facial nerve
      somatosensory evoked potentials (SEPs) by electrical stimulation of the Ramsay
      Hunt zone were presented. In the clinical phase of this work, we have tested 8
      normal subjects and 5 patients with unilateral peripheral facial palsy by the SEP
      method. Significant and reproducible responses were obtained in the normal
      nerves; general wave-form and different parameters are described: latency of
      different activities, differences inter and intra-subjects. In one case, we
      performed a brain mapping by stimulation of the Ramsay-Hunt zone to improve the
      localization of the different activities and to differentiate them from a
      possible auditory response to the electrical stimulation. In the pathological
      nerves, we observed significant changes in the morphology of the cortical waves
      with regards to the healthy nerves. Detailed results are presented in two cases
      with a long-term follow-up. We concluded that the electrical stimulation of the
      Ramsay Hunt zone evokes a cortical response like the electrical stimulation of
      other cutaneous zones. This response is significantly altered in peripheral
      facial palsy. Following studies should define the prognostic value of such
      modifications.

PMID- 1344563
TI  - Physiological bases and a technique for testing the full range of vestibular
      function.
AB  - The vestibulo-ocular reflex (VOR) is most active at higher frequencies (> 2 Hz)
      during locomotion, in order to stabilize vision. Use of active head movements,
      monitored by a sensor on a head strap, is a new method of testing the horizontal
      and vertical VORs which utilizes this natural frequency range, and doesn't
      require a rotating chair. Specialized computer processing based on Fourier
      analysis is necessary to analyze head and eye signals, which can be erratic.
      Higher harmonics of these erratic movements are particularly useful for VOR
      testing, in the analogous sense that complex sound processing is necessary for
      speech processing in audition. Use of portable computers with VOR active head
      analysis can be done at the bedside, as a portable vestibular test. Sophisticated
      software can effectively substitute for rotating chair hardware, provided that
      physiological corrections are applied to actively-generated movements at higher
      frequencies. In summary, the resulting test is brief, comfortable to the patient,
      portable, and useful for diagnostic screening over the frequency range that is
      most active during common daily movements.

PMID- 1344564
TI  - Retrolabyrinthine vestibular neurectomy. 10 years' experience.
AB  - The advances in the diagnosis of the vertigo patient and in the transtemporal
      approach to the cerebellopontine angle, have promoted the development of the
      retrolabyrinthine vestibular nerve section, for the surgical treatment of vertigo
      with hearing preservation. In a 10 years period (1982-1992), 45 patients
      underwent a vestibular nerve section through the retrolabyrinthine approach. The
      vertigo was controlled in 95% of the entire series, with 86% of hearing
      preservation, 6% of hearing improvement and 6% of hearing loss.

PMID- 1344565
TI  - Malformations of the inner auditory canal.
AB  - Malformations of the internal auditory meatus (I.A.M.) are often accompanied by
      other radiological abnormalities affecting the entire inner ear. In our series of
      cases we demonstrate solitary deformities of the IAM ranging from the stenosis of
      the canal (4 cases) to extreme narrowing (2 cases) or complete atresia. Another
      anomaly is the presence of a thick bony wall dividing the canal in two separate
      compartments, superior and inferior (3 cases). Most of the cases of solitary
      malformations were unilateral; they can be diagnosed at any age, considering that
      the patient has normal hearing in the opposite ear. When the malformation of the
      IAM occurs, associated with major deformities of the labyrinth (5 cases), we
      found an abnormal communication of CSF to the tympanic cavity, due to a severe
      anomaly of the fundus of the IAM. Meningitis is a frequent complication in
      patients with this abnormality.

PMID- 1344566
TI  - Cerebrospinal fluid fistula: frequency in head injuries.
AB  - The authors present 11,074 patients with head trauma managed in the Xoco and
      Juarez Hospitals from Mexico City, from 1980 through 1990. They report a
      frequency of cerebrospinal fluid fistulas in 1.3% of head trauma: 55% were
      anterior fossa fistulas and 39% middle fossa fistulas. The most common symptoms
      and the treatment are presented.

PMID- 1344567
TI  - [Authors' technique for the reconstruction of mastoidectomy cavities].

PMID- 1344568
TI  - [Bone-anchored epitheses and audioprostheses: 4 years' experience with the
      Branemark system in Germany].
AB  - Osseointegration describes direct contact between titanium and vital bone. The
      Branemark System uses this principle for bone anchorage of hearing aids and
      craniofacial prostheses. The experience made in the ENT Department of the
      University Hospital in Homburg/Germany with this procedure in the last 4 years is
      described. During this period, 40 patients have been operated and 119 titanium
      fixtures have been implanted. 30 patients got bone anchored prostheses (ear, nose
      or orbit) and 25 patients received bone anchored hearing aids. The large group of
      15 patients with congenital ear malformation presented both indications. 100 out
      of 119 implants i.e. 84% caused no major problems. The most frequent
      complications were granulations (10 implants i.e., 8.4%). More severe problems as
      non-integration of three pillars or rejection of one pillar were rare. Our
      experience for 4 years in an important number of patients was very positive in
      the majority of cases and allows us to consider the bone anchorage of hearing
      aids and craniofacial prostheses as a major advance in craniofacial
      rehabilitation and audiology.

PMID- 1344569
TI  - [Osseointegrated implants in facial prosthesis and hearing aids].
AB  - The principles of osseointegration defined by Branemark are reviewed. The authors
      describe the otological applications of titanium implants: bone anchorage hearing
      aids (B.A.H.A.) and ear epitheses. Obtaining good results depends on the
      selection of the patients and the observance of a rigorous technique.

PMID- 1344570
TI  - [Maxillofacial prosthesis, fixation by endo-osseous implants and transcutaneous
      pillars].
AB  - Osseointegrated facial prostheses are an interesting solution in maxillo-facial
      rehabilitation when reconstructive plastic surgery is not envisageable. Authors
      report two cases and give their opinion on the use of this kind of prostheses.

PMID- 1344571
TI  - Laparoscopic cholecystectomy combined with endoscopic sphincterotomy and stone
      extraction or laparoscopic choledochoscopy and electrohydraulic lithotripsy for
      management of cholelithiasis with choledocholithiasis.
AB  - Six hundred twenty-two laparoscopic cholecystectomies were performed at St.
      Vincent Hospital over a 14-month period. We reviewed the records of 366 of these
      patients who were referred to the authors. Thirty-six patients had suspected
      choledocholithiasis. The primary author (M.E.A.) performed 38 endoscopic
      retrograde cholangiopancreatography (ERCPs) on these patients for diagnosis and
      management. Seventeen of the 36 patients had common bile duct stones; 19 patients
      had negative studies. Of the 17 patients with choledocholithiasis, 15 had
      successful cannulation of the common bile duct, and, of these, 10 underwent
      laparoscopic cholecystectomy plus endoscopic sphincterotomy and extraction of the
      common duct stone(s). In one high-risk elderly patient, we extracted the stone
      from the common duct and left the gallbladder in situ. Two patients failed
      endoscopic cannulation and underwent open cholecystectomy with common bile duct
      exploration. Four additional patients, cannulated successfully, had unsuccessful
      endoscopic stone removal because the stones were too large or were impacted. Two
      of these patients underwent open cholecystectomy and common duct exploration. The
      two other patients underwent laparoscopic cholecystectomy and choledochoscopy
      through the cystic duct with the flexible choledochoscope. An electrohydraulic
      lithotripsy probe was then inserted through the choledochoscope to fragment the
      stones, and stone fragments were allowed to pass through the previously created
      sphincterotomy. We believe our data, supported by data in the literature, show
      that these alternative methods for treating choledocholithiasis are safe and
      effective and should be considered primary modalities for treating this condition
      now that laparoscopic cholecystectomy is the treatment of choice for
      cholelithiasis.

PMID- 1344572
TI  - The endoscopic Congo red test during proximal gastric vagotomy: an essential
      procedure.
AB  - A previously described method for evaluating the completeness of proximal gastric
      vagotomy (PGV), the intraoperative endoscopic Congo red test (ECRT), may allow
      for a more complete parietal cell denervation and thus result in a lower long
      term incidence of postvagotomy ulceration. Of 20 patients undergoing PGV, 12
      (60%) required further gastric denervation after intraoperative ECRT of the
      following sites: right gastroepiploic nerve (7), the nerve of Grassi (4), and the
      lesser curvature (3). Confirmation of completeness of PGV by the ECRT was easily
      performed and ensured intraoperative quality control. The routine performance of
      intraoperative ECRT during PGV may ultimately decrease the incidence of
      subsequent recurrent ulceration.

PMID- 1344574
TI  - What should a "surgical endoscopist" do?

PMID- 1344573
TI  - Comparative surgical and colonoscopic appearance of colon anastomoses constructed
      with sutures, staples, and the biofragmentable anastomotic ring.
AB  - The following animal study was undertaken to compare and assess the endoscopic
      gross appearance and histology of colonic anastomoses constructed with sutures,
      staples, and the biofragmentable anastomotic ring (BAR). METHODS: Three
      anastomoses--1 BAR, 1 stapled, and 1 sutured--were placed in each of 48 dogs and
      colonoscopy and anastomotic evaluation were done. RESULTS: No leaks were found by
      air insufflation at surgery. Grossly, the BAR had serosal hematomas in 27/48
      anastomoses vs 7/48 for stapled and 1/48 for sutured (BAR vs stapled P < 0.0005
      and sutured vs stapled P = 0.07). Adhesions were significantly greater for BAR
      (35/36) and sutured (34/36) compared to stapled (26/36) (BAR vs stapled P = 0.01
      and sutured vs. stapled P = 0.04). Colonoscopic exams at days 3, 7, and 28 showed
      no significant difference among groups with respect to bleeding, ulceration,
      necrosis, granulation, or contour. Sutured anastomoses were more stenotic (24/31)
      than stapled (4/31) or BAR (3/31) ones (BAR vs sutured and sutured vs stapled P <
      0.005). At 28 days, 10/10 sutured vs 2/10 stapled vs 3/10 BAR were stenotic (BAR
      vs sutured P = 0.02, sutured vs stapled P = 0.01). Inflammation on histologic
      exam at 28 days was not significantly different: sutured (12/12), stapled
      (12/12), or BAR (9/12). Fibrosis was more prominent in sutured (12/12) than in
      stapled (5/12) or BAR (4/12) anastomoses (BAR vs sutured P = 0.001, sutured vs
      stapled P = 0.004, and BAR vs stapled P = 1.00). All anastomoses healed primarily
      without necrosis or obstruction. CONCLUSIONS: (1) Colonoscopy to evaluate
      anastomoses can be done safely even in the early post-operative period. (2) The
      BAR anastomoses had the most serosal hematomas; BAR and sutured had more
      adhesions than stapled anastomoses; and sutured anastomoses had the most stenosis
      and fibrosis. None of these differences was of clinical significance.

PMID- 1344575
TI  - Pelviscopic uterine surgery.
AB  - About 15-20% of the time uterine surgery via laparotomy is replaced in our
      department by operative pelviscopy. Of these, in reference to myoma surgery,
      about 70% were tackled with operative pelviscopy and a laparotomy was avoided.
      This allows the preservation of the uterus, especially for those women who desire
      to bear children in the future. Organ-preserving, minimally invasive surgery is
      the current accepted operative ideal. Postoperative sequelae like adhesion
      formation, subacute intestinal obstruction, and chronic abdominal pain are thus
      decreased. The importance of correct and safely functioning equipment and
      instruments cannot be overstressed for optimal results. A closed drain, i.e., the
      Robinson drainage system, can be kept in place for at least 12-24 h to check the
      postoperative ooze. In two cases of extensive ooze, repeat pelviscopy was
      performed within 12 h and hemostasis was achieved by the use of endosutures and
      endocoagulation.

PMID- 1344576
TI  - T-tube placement during laparoscopic cholecystectomy.
AB  - The management of common bile duct stones during laparoscopic cholecystectomy can
      pose a challenge to the surgeon as no definitive management plan is universally
      accepted at this time. We present a case where a common bile duct exploration was
      performed through a choledochotomy, describing how the t-tube was placed.

PMID- 1344577
TI  - Bile leak after laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy has now become the preferred surgical approach to
      symptomatic cholelithiasis. With the widespread use of this technique there have
      appeared reports of complications. We report the case of a patient who developed
      a cystic duct stump bile leak after laparoscopic cholecystectomy. Percutaneous
      drainage of the biloma, endoscopic retrograde cholangiopancreatography and
      papillotomy led to resolution of the problem. The literature on cystic duct stump
      leaks after laparoscopic cholecystectomy is reviewed and the various therapeutic
      modalities are outlined.

PMID- 1344578
TI  - Peroral enteroscopic removal of a retained percutaneous transhepatic guidewire
      from the jejunum using a colonoscope.
AB  - Several authors have described the ability to perform small-intestine endoscopy
      with long, flexible fiberscopes. A peroral colonoscope has been used for small
      bowel enteroscopy and biopsy. A pediatric colonoscope for jejunoscopy has been
      described. Herein we report a patient undergoing percutaneous transhepatic
      decompression for the extrahepatic biliary obstruction in whom the guidewire
      broke and was lost in the liver. The proximal end of the wire was within the
      liver, while the distal end exited the ampulla and lay within the upper jejunum.
      Utilizing a peroral approach with the flexible pediatric colonoscope, we
      recovered the guidewire without advancing it further into the jejunum, where it
      may have been lost and have necessitated a celiotomy.

PMID- 1344579
TI  - Peroral tunable-dye laser lithotripsy of intrahepatic stones in oriental
      cholangitis.
AB  - This case report details the use of a pulsed tunable-dye laser lithotripter in
      the endoscopic management of recurrent intrahepatic stones in a patient with
      Oriental cholangitis. A 42-year-old Chinese man had a cholecystectomy and
      choledochoduodenostomy in 1980. Subsequently he had three episodes of recurrent
      cholangitis which responded to medical treatment. The patient presented in April
      1989 with a fourth attack of cholangitis. Endoscopic retrograde
      cholangiopancreatography (ERCP) and ultrasound demonstrated a large mass of
      stones in the right intrahepatic ductal system. A flexible upper gastrointestinal
      endoscope was passed into the right hepatic duct via the choledochoduodenostomy.
      The stones were fragmented with a tunable-dye laser and the residual fragments
      were removed endoscopically.

PMID- 1344581
TI  - Therapeutic laparoscopic suturing techniques.
AB  - With the introduction of the technique of Interventional laparoscopy, a new era
      of minimally invasive general surgery has begun. The well-established principles
      of general surgical technique have not been altered by this new technology. As
      the new laparoscopic technology has become available, intraabdominal laparoscopic
      suturing and ligating techniques have been developed. The authors have attempted
      to elucidate the techniques of endoligation, "Endoloop" application, endosuture
      placement, sling suture placement, and continuous suture placement in
      laparoscopic surgery.

PMID- 1344582
TI  - Capnograph locates gas leaks in laparoscopy.

PMID- 1344580
TI  - Mechanism of thrombosis caused by sclerotherapy of esophageal varices using
      sodium tetradecyl sulphate.
AB  - The mechanism of thrombosis following intravariceal injection of sodium
      tetradecyl sulphate (S.T.D.) was investigated with respect to effects on the
      vascular endothelium, the coagulation cascade, and platelet function. Using an
      umbilical cord model designed to simulate blood flow over the endothelium, it was
      found that S.T.D. is a potent toxin for endothelial cells in that brief exposure
      to even low concentrations of the agent were effective in stripping endothelium
      over a considerable distance, exposing highly thrombogenic endothelium in the
      process. Effects on coagulation and platelet function were found to be dependent
      on concentration. Diluted S.T.D. induced a hypercoagulable state, possibly in
      consequence of a selective inhibition of the physiological anticoagulant, protein
      C, and promoted platelet aggregation. Higher concentrations inactivated the
      coagulation cascade and lysed platelets completely. These results suggest that
      intravariceal infusion of S.T.D. at considerable dilution may be at least as
      effective in inducing thrombosis as standard dosage, and possibly more so.

PMID- 1344583
TI  - Thoracoscopic dissection of the esophagus: an experimental study.
AB  - In order to reduce the respiratory morbidity of thoracotomy in esophageal
      surgery, several methods have been used, such as blunt dissection and endoscopic
      dissection through mediastinoscopy. It seems that the latter reduces drastically
      the morbidity but does not allow full visualization of the esophageal wall, a
      disadvantage in some circumstances. We describe a thoracoscopic dissection of the
      esophagus which gives a large and magnified view of the pleural cavity, of the
      mediastinum, and of the esophagus.

PMID- 1344584
TI  - Endoscopic evaluation of gastric cancer infiltrating the lower esophagus.
AB  - Endoscopic and histopathological findings were compared in 74 patients with
      gastric cancer infiltrating the lower esophagus who had undergone gastrectomy to
      evaluate mode of esophageal infiltration. There were no early cancers. Cancer
      infiltration modes were histopathologically broken down into three types:
      superficial, whole layer, and deep layer. Endoscopic findings were broken down
      into five types for proximal infiltration. Endoscopy used for histological
      evaluation frequently revealed the protruded type to be whole layer and had a
      highly accurate diagnosis rate (94%); it revealed the histology of the other four
      types to be primarily superficial. Extent of cancer invasion was underestimated
      in giant-rugae tumors (40%), as endoscopy could barely detect the small nest of
      esophageal infiltrations. Lugol staining was useful in preventing
      underestimation. For flat cancer, which is poorly demarcated and is often
      accompanied by vascular invasion, preoperative evaluation is very difficult,
      requiring preoperative examination of a frozen section taken from the proximal
      edge of resected specimen.

PMID- 1344585
TI  - Acute acalculous cholecystitis in severely traumatized patients: a prospective
      sonographic study.
AB  - Acute acalculous cholecystitis is a well known complication in severely
      traumatized patients. Existing data originate from retrospective analyses and
      episodic case reports. In a prospective ultrasonographic study 25 polytraumatized
      patients admitted to our intensive care unit between January 1, 1989, and
      December 31, 1989, were examined in daily intervals for this condition. Trauma
      scoring was performed according to the injury severity score (ISS) and polytrauma
      score (PTS). "Stress cholecystitis" was defined as a combination of hydrops of
      the gallbladder, an increased mural thickness (> 3.5 mm), and the demonstration
      of "sludge." We were able to demonstrate this diagnostic triad in four out of 25
      patients (= 16%). As a consequence early elective cholecystectomy was done in one
      patient. The remaining patients were treated conservatively. The incidence of
      stress cholecystitis in severely traumatized patients is probably higher than
      figures so far published suggest. Ultrasonography is a reliable method of early
      detection and follow-up for this complication.

PMID- 1344586
TI  - Hemobilia--successful treatment by angiographic embolization.
AB  - Hemobilia after major liver trauma is a difficult problem to manage. We report a
      case of an 18-year-old male who sustained major liver trauma. Bleeding was
      controlled at laparotomy. Seventeen days after surgery hematemesis and
      intermittent bleeding from the drain occurred. Hepatic artery angiography
      demonstrated a pseudoaneurysm of one of the branches. Gelfoam embolization
      successfully controlled the bleeding. Review of the literature reveals that
      hemobilia has been treated by a conservative means as well as by surgery. Hepatic
      angiography to localize the site of bleeding and then embolization to control the
      hemorrhage now constitute the preferred method of treatment.

PMID- 1344587
TI  - Laser-assisted removal of a foreign body from the colon.
AB  - An 81-year-old woman underwent a colonoscopy because of a sigmoiditis poorly
      responding to conservative therapy. A rod-shaped foreign body found in the sigma
      proved impossible to remove conventionally. Irradiation with a low laser energy
      caused the foreign body to break apart, after which its extraction was
      straightforward. The further clinical course was uncomplicated. In this case a
      partial sigmoidectomy would have been indicated had the laser-supported
      extraction not been successful. The authors suggest that a similar procedure
      could be helpful in the management of foreign bodies in the esophagus.

PMID- 1344588
TI  - New endoscopic surgery instrument: separator combined with sound for lavage and
      aspiration.

PMID- 1344590
TI  - The "shuttle" stone collector--a new device for collecting lost gallstones in
      laparoscopic cholecystectomy.

PMID- 1344589
TI  - Frontiers in general surgery: pioneers, cowboys and desperados.

PMID- 1344591
TI  - Effect of herbicides on human skin. Penetration of herbicides through the
      epidermis "in vitro".
AB  - Penetration of herbicides GRAMOXONE and REGLONE through human epidermis was
      studied "in vitro". A special diffusion equipment was used and the method of
      Calderbank and Yuen was modified for quantitative determination of efficient
      components (paraquat, diquat) of both herbicides. Penetration of the chosen
      herbicides was different and surfactants contained in herbicides were found to
      play a role in penetration into the skin.

PMID- 1344592
TI  - Experimental nonspecific immunostimulation by the Propionibacterium acnes
      vaccine.
AB  - The immunostimulation effect of the selected Propionibacterium acnes strain 16073
      was described. The optimal conditions for the preparation of the P. acnes vaccine
      and the nonspecific immunostimulation effects of the vaccine on various
      experimental infections were evaluated.

PMID- 1344594
TI  - [Magnesium in cardiology].

PMID- 1344593
TI  - Metabolic changes in various types of recurrent urolithiasis.

PMID- 1344596
TI  - Effect of physical load on the platelet function and ultrastructure in patients
      with ischemic heart disease.
AB  - The aggregability of the blood platelets and their ultrastructure were examined
      during the bicycle exercise test in 20 patients with ischemic heart disease and
      stable angina pectoris. In 8 patients with unequivocally positive exercise test a
      significant increment of stimulated aggregation from 58.2 (CV7%) to 71.2 (13.6%)
      resulted in comparison with a group of patients who did not fulfilled criteria of
      exercise testing. In this group the aggregability dropped from 56.0 (5%) to 38.7
      (8.4%) eventually. No changes in a diameter and shape were observed during the
      exercise test was positive the amount of granules decreased. It is considered to
      be an indirect proof of the functional changes in thrombocytes during a certain
      rise in aggregability.

PMID- 1344595
TI  - Immunohistochemical determination of some tumour markers (blood group antigens A,
      B, H, T-antigen, CEA) in colonic and rectal tissue after endoscopic polypectomy.
AB  - The expression of blood group antigens A, B, H, T-antigen and CEA was determined
      in tissue samples of polyps of the rectosigmoideum removed by endoscopic
      polypectomy. On average 39 months later, during colonoscopic examination bioptic
      samples were removed at the site of previous polypectomy and the expression of
      the same tumour markers as previously was determined. In contrast to literary
      data, the cellular expression of blood group antigens was demonstrated only in
      one case out of seven adenomas of the rectosigmoideum. On the other hand,
      cellular expression of blood group antigen B was found in 6 cases at the site of
      previous polypectomy and in 6 cases, this antigen was incompatible.
      Interpretation of these results is difficult at this time.

PMID- 1344597
TI  - Dextrocardia and Marfan's syndrome.
AB  - It is described the occurrence of dextrocardia together with the congenital
      cyanotic heart disease in 20 year old man included in the fruste forme of the
      Marfan's syndrome. The diagnosis was made by the physical examination with the
      evidence of the arachnodactyly by the metacarpal indices and confirmed by autopsy
      with the following results: dextrocardia, large atrial septal defect, common
      ventricle, atresia of the pulmonary artery with the collateral lung perfusion
      from the descending aorta. There were found neither ocular manifestations, nor
      unambiguous manifestations of the aortic lesions. The ultrastructural
      examinations showed only greater accumulation of the PAS positive substances.
      Dextrocardia as the cardiovascular manifestation of the Marfan's syndrome has not
      yet been reported in the available literature.

PMID- 1344598
TI  - Prognostic value of electrocardiographic stress testing compared to thallium
      scintigraphy.
AB  - The highly sensitive and specific thallium scintigraphy is compared to loading
      electrocardiography with regard to the two crucial parameters: loaded angina
      pectoris (AP) and horizontal or descendant depression of ST segment of 1.5 mm and
      deeper (ST). Effectiveness of loading ecg test was determined quantitatively in
      terms of sensitivity, specificity, prognostic value and test accuracy. Those
      criteria of positivity of the loading test showed that sensitivity was higher for
      AP than for ST (73% and 63%, resp.), but specificity was higher for ST (100%)
      than for AP (79%). The result of thallium test was estimated according to AP
      occurrence with 80% probability for positive prognosis and 70% probability for
      negative prognosis; with ST, probability of positive prognosis was 100% and that
      of negative prognosis was 69%. Test accuracy is 75% for AP and 79% for ST. The
      100% probability of positivity of thallium scintigraphy in ST depressions of 1.5
      mm and deeper discredits indication of this method in this cases. In the absence
      of ST depressions, the origin of typical pain during the loading ECG enhances
      probability of positivity of thallium scintigraphy more than twofold (53 vs.
      21%).

PMID- 1344599
TI  - [Histochemical differentiation of the pancreas in the human embryo].

PMID- 1344600
TI  - Can arachnoidal adhesions lead to hypoperfusion of the nervous tissue?
AB  - The author presents the possible mechanism that probably lead to deterioration of
      neurological finding after changes of parenchymatous pressure of neural tissue in
      the course of lumbar puncture, ventriculography or some neurosurgical
      interventions. The possible cause are arachnoidal adhesions impeding free
      circulation of cerebrospinal fluid. "Trapped" cerebrospinal fluid leads to the
      ischemia of the neural tissue because of relative increasing of cerebrospinal
      fluid pressure.

PMID- 1344601
TI  - [Current possibilities in the diagnosis of brain abscesses].

PMID- 1344602
TI  - Radio-chemotherapy in the treatment of advanced cancer.
AB  - Tests in vitro and first clinical studies proved a radiosensitizing effect of
      cisplatin. In our study 40 patients with advanced resistant cancer of head, neck,
      lungs and rectum were treated by conventional radiotherapy and cisplatin. The
      drug was administrated in 10 mg after each irradiation. The tumor dose varied
      between 30-50 Gy in 3-5 weeks, within the total dose cisplatin 150-250 mg. In
      more than 70% of cases remarkable retreat of tumors, in some cases even a
      complete regression, were observed. Adverse reactions and toxicity often
      associated with administration of platin were very mild, so that even patients in
      rather poor physical condition could have been treated. Having performed no
      special hydratation serious nephrotoxicity was never observed. The potentiation
      of radiation by cisplatin can be therefore considered a relatively harmless
      treatment of inoperable advanced cancers useful especially in cases where other
      forms of palliative treatment have been exhausted or not feasible.

PMID- 1344603
TI  - Long-term prognosis of prehepatic portal hypertension.
AB  - The study is a report of the long-term follow-up of 53 patients with prehepatic
      portal hypertension, their life and work conditions. The average time of the
      follow-up was 25 years. It was concluded, that the long-term prognosis is derived
      from the development of the disease, its recognition, the used therapy and from
      the function of the patient's liver. From the battery of therapeutic modalities a
      very good experience has been achieved with the endoscopic treatment of bleeding
      varices. The portosystemic shunt is a pathophysiologically well justified but
      selective procedure, which is indicated in about 20% of bleeding patients. The
      long-term prognosis of the disease was found good in 75% of patients.

PMID- 1344604
TI  - [Early subacute complications from arteriovenous fistulas in extracorporeal
      hemodialysis].

PMID- 1344605
TI  - Cryosurgery in neovascular glaucoma.
AB  - Cryocoagulation was used to treat 21 eyes with neovascular glaucoma. In 6 eyes,
      cyclocryocoagulation was used as an independent method and in 15 eyes
      cyclocryocoagulation and following transscleral panretinal cryocoagulation in one
      session. The author has followed up the postoperative development of the
      intraocular pressure, pain in the eye, rubeosis iridis, and the central visual
      acuity. Markedly better results were achieved by the author by using the combined
      cryosurgical method. The author assumes the cause of the unsatisfactory final
      central visual acuity to be the rather late treatment of the neovascular glaucoma
      most of the patients were operated on 2 to 3 weeks after the acute increase of
      the intraocular pressure. A good final central visual acuity was achieved in
      patients who were operated on immediately after the acute increase of the
      intraocular pressure. After the use of the combined cryosurgical intervention, we
      noted in all the patients: within 3 days normalization of the intraocular
      pressure in all the patients, on the first postoperative day a marked relief from
      pain in all the patients and, also in all the patients, a marked regression of
      rubeosis iridis within 6 weeks after operation.

PMID- 1344606
TI  - Neovascular glaucoma and intraocular pressure: II. Reduction of intraocular
      pressure--our 5-year experience.
AB  - The paper reports the results obtained with reduction of intraocular pressure in
      38 eyes of 38 patients with acute neovascular glaucoma. Cyclocryocoagulation
      alone was made in 12 eyes, 26 eyes were treated by transscleral panretinal
      cryocoagulation combined with cyclocryocoagulation. In eyes treated by
      cyclocryocoagulation alone the intraocular pressure less than 26 mmHg was on 5th
      day after operation in 41.6%, on 10th day in 66.7%. However, this effect was
      transient in one-third of the patients, and no effect was found in one-third of
      eyes. In eyes treated by transscleral panretinal cryocoagulation combined with
      cyclocryocoagulation, the intraocular pressure less than 26 mmHg by 3 days after
      operation was recorded in 50%, by 10 days in 76.9%. Postoperative hypotension
      developed in 27%. It is concluded that intraocular pressure in neovascular
      glaucoma is better managed by transscleral panretinal cryocoagulation with
      concurrent cyclocryocoagulation than by cyclocryocoagulation alone.

PMID- 1344607
TI  - Preliminary experimental experiences with xenotransplantations.
AB  - In our xenotransplantation experiments has been a major aim to induce specific
      tolerance. The results from the meeting of the donor's and the recipient's
      immunocompetent systems already in the period of embryonic development and/or the
      influence of methylprednisolone are described.

PMID- 1344608
TI  - Secondary Hodgkin's disease in polymyositis and type 1 diabetes mellitus after a
      long-term immunosuppressive treatment.
AB  - Immunological disorders can play an important role in the etiopathogenesis of
      malignant lymphogranuloma. The authors demonstrate a patient with autoimmune
      polymorbidity (polymyositis and type 1 diabetes mellitus) which underwent a long
      term immunosuppressive and cytostatic therapy. After 7 years of that treatment,
      Hodgkin's disease of mixed cellularity type developed. The clinical findings of
      the case are described and the clinical particularities along with possible
      mutual links among these diseases are stressed.

PMID- 1344609
TI  - Toxic effect of lead of mice testicles after its administration with drinking
      water.
AB  - The experiments were carried out with male mice of the strain CBA x C57BL/10.
      Lead dinitrate was added to drinking water to obtain the final lead concentration
      of 0.05 g/l. The material was removed on the 1st, 2nd, 3rd, 4th and 5th week.
      Testicles were removed fixed in the mixture of neutral formol and 3% K2Cr2O7.
      Tissue samples were processed by routine procedure and stained with HE and PAS. A
      relative volume proportion of seminiferous tubules and of interstitial tissue of
      the testicles was determined by the method of point counting. The first changes
      in the germinal epithelium of seminiferous tubules were found on the 2nd week
      after the application. Atypical cells varying in size up to large multinuclear
      cells were present. With a prolonged time of exposition they multiplied and
      various dystrophic changes up to disintegration of cells of the germinal
      epithelium occurred. The experimental groups showed (compared to controls) an
      increased volume of interstitial tissue. A prolonged exposition led to a marked
      enlargement of the interstitial tissue.

PMID- 1344610
TI  - [The education of the nutritionist and dietician in Puerto Rico].

PMID- 1344611
TI  - [New pathways for teaching about food and nutrition].

PMID- 1344612
TI  - [The present situation of vitamin A deficiency in Latin America and the
      Caribbean].

PMID- 1344613
TI  - Vitamin A deficiency as a public health problem & assessment methods.

PMID- 1344614
TI  - [Central America and Panama: an experience in the education and training of human
      resources in food and nutrition].

PMID- 1344615
TI  - [Interventions for the prevention and control of vitamin A deficiency in Latin
      America and the Caribbean].

PMID- 1344616
TI  - Etiology of obesity: genetic factors.

PMID- 1344617
TI  - Insulin resistance in obesity.

PMID- 1344618
TI  - The uses of software in nutrition analysis workshop.

PMID- 1344619
TI  - [The development and evaluation of formulas for supervising the professional
      performance of the nutritionist].

PMID- 1344620
TI  - [The problems, focus and strategies in support of the education and training of
      human resources in food and nutrition].

PMID- 1344621
TI  - [Food and nutritional surveillance].

PMID- 1344622
TI  - [The street sales of food and the cholera epidemic in Latin America].

PMID- 1344623
TI  - [The interactive effects of food and diarrheal diseases on growth and
      anthropometric measures].

PMID- 1344624
TI  - The dietary management of acute childhood diarrhea: optimal timing of feeding and
      appropriate use of local mixed diets.

PMID- 1344625
TI  - Use of milk in infants with diarrhea.

PMID- 1344626
TI  - [The effects of diarrhea on trace nutrients].

PMID- 1344627
TI  - [Oral rehydration solutions based on cereals].

PMID- 1344628
TI  - Nutrition and oral health.

PMID- 1344629
TI  - Fluoride in oral health.

PMID- 1344630
TI  - The safety and effectiveness of fluoridation of community drinking water
      supplies.

PMID- 1344631
TI  - [A master's degree in the health sciences with a concentration on nutrition].

PMID- 1344632
TI  - [The water fluoridation situation in Puerto Rico].

PMID- 1344633
TI  - [Nutrition, aging and urbanization: an integral focus in research].

PMID- 1344634
TI  - [The factors potentially conditioning the food habits of older Guatemalans from a
      suburban area].

PMID- 1344635
TI  - [Nutrition and aging: a commentary and conclusions].

PMID- 1344636
TI  - [Body composition and aging: methods and models applied to the study of aging].

PMID- 1344637
TI  - Death scene gas analysis in suspected methane asphyxia.
AB  - Two cases of methane asphyxia occurring in two boys (age 11 and 12 years) who
      were found at the bottom of a 37-ft (11.1-m)-deep sewer shaft are described.
      Attempted resuscitation of the first patient was unsuccessful and achieved only
      temporary stabilization of the second, who died 48 h after his discovery.
      Autopsies revealed relatively minor multifocal traumatic injuries, with evidence
      of hypoxic-ischemic encephalopathy in the patient who survived for 2 days.
      Subsequent analysis of gas in the shaft revealed 21% oxygen at the surface, 14.3%
      at a depth of 5 ft (1.5 m), and only 4.8% at depths of 10 ft (3 m) and below.
      Other gases detected at the lower levels were methane, nitrogen, and carbon
      dioxide (4.3%). These cases demonstrate the value of atmospheric gas analysis in
      cases of possible methane asphyxia in confirming the presence of methane and in
      demonstrating levels of oxygen below that necessary to support life.

PMID- 1344638
TI  - Are there basic emotions?
AB  - Ortony and Turner's (1990) arguments against those who adopt the view that there
      are basic emotions are challenged. The evidence on universals in expression and
      in physiology strongly suggests that there is a biological basis to the emotions
      that have been studied. Ortony and Turner's reviews of this literature are
      faulted, and their alternative theoretical explanations do not fit the evidence.
      The utility of the basic emotions approach is also shown in terms of the research
      it has generated.

PMID- 1344639
TI  - The area between curves (ABC)--measure in nutritional anthropometry.
AB  - This paper considers a statistic--recently suggested by Mora--for the deviation
      of a sample distribution from a reference distribution which typically arises in
      anthropometry when using the nutritional indicators height/age, weight/age or
      weight/height. The statistic measures the area between curves (ABC) and stands
      for the mass of the sample distribution which is not covered by the reference
      distribution. The paper provides a statistical framework for the ABC and includes
      some minor corrections of Mora's original paper. For the normal distribution
      situation with common or different variances, formulae are derived which include
      a partition of ABC into parts corresponding to malnourished and well-nourished
      groups. However, the main result is a non-parametric generalization of the ABC,
      motivated by the fact that the nutritional indicators often have skewed
      distributions with heavier left tails. Non-parametric statistical inference is
      provided by linking the ABC to the Kolmogorov-Smirnov statistic.

PMID- 1344640
TI  - Acquired lacrimal drainage obstruction: an etiologic classification system, case
      reports, and a review of the literature. Part 2.

PMID- 1344642
TI  - Peripartum cerebral venous thrombosis.
AB  - The clinical and computed tomography (CT) features of 25 patients with peripartum
      CVT are described. Majority of the patients presented in postpartum period and
      did not receive proper antenatal care. Headache (92%), altered sensorium (80%,
      seizures (76%), papilloedema (80%) and hemiplegia (52%) were the common modes of
      presentation. CT findings included diffuse brain oedema (52%), haemorrhagic or
      nonhaemorrhagic infarctions on one or both sides of brain (48%), gyral
      enhancement (40%) and tentorial enhancement (16%). While 15 patients made good
      recovery, 3 cases (12%) died during acute stage of illness.

PMID- 1344641
TI  - Capnography and awareness.

PMID- 1344643
TI  - Acute renal failure secondary to myoglobinuria.
AB  - Acute Renal Failure (ARF) secondary to rhabdomyolysis and myoglobinuria was seen
      in four patients. In three, this was secondary to trauma and the fourth patient
      had an inflammatory myositis. All 4 patients had total recovery of renal
      function.

PMID- 1344644
TI  - Lipoproteins: what, when, and how often to measure.

PMID- 1344645
TI  - Aortic dissection.

PMID- 1344646
TI  - The retroviruses: classification and molecular biology.

PMID- 1344647
TI  - Central nervous system opportunistic infections in HIV disease: clinical aspects.
AB  - Nervous system opportunistic infections are seen in about one fifth of AIDS cases
      and account for over 40% of the patients with neurological manifestations.
      Serious infections are seen in severely immunosuppressed patients, usually with
      CD4 counts of 200 ml-1 or less. The commonest is CMV, which can produce acute
      encephalitis, sometimes with focal hemisphere or brain-stem signs, dementia,
      retinitis, optic neuritis and an ascending radiculomyeloencephalitis.
      Cryptococcal meningitis is the most frequent fungal disease; a high degree of
      clinical suspicion is required in patients with fever, malaise, headache or
      seizures. Only CSF cultures are always positive; both serum and CSF cryptococcal
      antigen tests are highly sensitive and specific. Treatment with amphotericin B
      and flucytosine is successful in at least 70% of first episodes but side-effects
      are common. Without maintenance therapy 50% of patients relapse; fluconazole is
      recommended. Cerebral toxoplasmosis can present with focal cerebral or spinal
      cord signs but also as a diffuse encephalopathy; negative T. gondii serology is
      exceptional but positive serum titres are usually unhelpful. Treatment with
      sulfadiazine, pyrimethamine and folinic acid achieves good results in 90% of the
      first episodes, but side-effects are common. Appearances on CT scan or MRI may
      take several weeks to improve. The value of an empirical approach to treatment is
      well-established; an initial cerebral biopsy is difficult to justify. Without
      maintenance therapy a relapse rate of 50% can be expected; therapy with
      sulfadiazine and pyrimethamine may also prevent pneumocystosis. HIV disease
      appears to increase the likelihood of neurosyphilis, and the risk of relapse
      after conventional penicillin doses, in patients with syphilis; at least 3-4
      weeks of appropriate therapy are recommended. A number of other diseases caused
      by viruses, fungi, bacteria and parasites are less common; these include
      progressive multifocal leukoencephalopathy, herpes simplex and zoster infections
      and tuberculosis.

PMID- 1344648
TI  - Cognitive impairment and dementia in HIV-1 infection.

PMID- 1344649
TI  - Other neurological diseases in HIV-1 infection: clinical aspects.
AB  - HIV-1-related neurological diseases, excluding opportunistic infections and HIV
      encephalitis, are considered here. Most occur in severely immunosuppressed
      patients, with CD4 counts of under 200 x 10(6) l-1. Primary brain lymphoma and
      metastases from systemic non-Hodgkin's lymphoma, the second commonest cause of
      cerebral mass lesions in AIDS, are usually aggressive B cell tumours. Their poor
      median survival after treatment, compared with that of lymphomas in non-AIDS
      patients, seems related to systemic complications, particularly opportunistic
      infections. Kaposi's sarcoma produces neurological symptoms exceptionally.
      Cerebral infarction is often unrecognized clinically but large vessel arteritic
      occlusions may occur. Intracranial haemorrhages occur mostly in thrombocytopenic
      patients. Seizures are frequently referred to the neurologist; investigation may
      lead to a diagnosis of AIDS. Nearly 50% of patients with seizures have cerebral
      toxoplasmosis or cryptococcal meningitis; HIV-1 encephalitis is presumed to be
      the cause in 30%. A subacute or chronic vacuolar myelopathy with pyramidal and
      posterior column signs is the commonest form of spinal cord involvement in AIDS;
      its cause remains unknown. Peripheral nerve syndromes occur at all stages of HIV
      1 infection. Distal symmetrical peripheral neuropathies are the most frequent,
      particularly a painful form with axonal atrophy, associated with CMV infection,
      and seen during ARC or AIDS. Mononeuritis multiplex due to vasculitis, CMV, or
      lymphoma and a serious lumbosacral polyradiculopathy due to CMV are infrequent.
      The commonest myopathy is due to zidovudine (AZT); it usually responds to drug
      withdrawal. The nature, prognosis and optimal management of most other myopathies
      is yet to be determined.

PMID- 1344650
TI  - Neuropathology of HIV-1 and HTLV-1 infection.

PMID- 1344651
TI  - The immunology of retrovirus disease.

PMID- 1344652
TI  - Therapeutic aspects of retroviral disease.
AB  - Retroviruses of the nervous system cause HTLV-1-associated myelopathy and HIV
      associated diseases. The treatment of HTLV-1 disease is essentially conservative;
      there is no effective drug treatment and therefore patients should be simply
      supported and reassured. If appropriate, other members of the family should be
      tested for HTLV-1 disease and counselled. The effects of HIV on the nervous
      system are much more complex. Therapy must take account of the diverse
      complications of HIV disease. Patients are probably best managed in specialized
      clinics which can cope with the different manifestations of the disease.
      Zidovudine (AZT) is the only effective anti-HIV drug that is licensed. It is
      indicated in complicated seroconversion disease and for any manifestation of HIV
      progression including AIDS dementia complex. Management of severe neurological
      disease depends critically on the ability to diagnose and treat CNS-specific
      opportunistic infections. Whether zidovudine is indicated for early asymptomatic
      disease when CD4 counts are below 500 microliters-1 is controversial. The main
      problems of zidovudine are reversible anaemia which results in about 30% of
      patients not tolerating long-term use, and the development of drug resistance
      which may be associated with clinical failure of the drug. Other, new and
      experimental drug treatments are discussed but none of them has as yet shown any
      convincing evidence of efficacy. Future improvements in treatment appear to
      depend on the development of effective multiple drug regimens (concurrently or
      sequentially) which will overcome the challenge of drug resistance.

PMID- 1344653
TI  - Neurological aspects of lentiviral infections in animals.

PMID- 1344654
TI  - HTLV-1 and neurological disease.

PMID- 1344655
TI  - HIV-1 and HIV-2: overview of disease spectrum.
AB  - This overview has attempted to cover the more common aspects of the clinical
      presentations of HIV infection and the differential diagnoses. These can only be
      generalizations as presentations differ dramatically from patient to patient. It
      is also important to be aware that in an individual the disease is continually
      evolving and the same complication may produce very different clinical
      manifestations at different times. It is vital to have a high index of suspicion
      of the occurrence of complications and to treat promptly. Delay may not only make
      successful treatment more difficult but it is conceivable that it may exacerbate
      the underlying immunodeficiency and hasten progression of disease.

PMID- 1344656
TI  - Chemotactic cytokines in the epidermis.

PMID- 1344657
TI  - Molecular biology and pathology of type VII collagen.
AB  - Type VII collagen is a genetically distinct member of the collagen family of
      proteins. Type VII collagen has been shown to be the major component of anchoring
      fibrils, attachment complexes which secure the cutaneous basement membrane of the
      skin to the underlying dermis. Understanding of the structure of type VII
      collagen has been advanced by recent cloning of the corresponding gene.
      Chromosomal mapping of the gene to the short arm of chromosome 3 and
      identification of intragenic polymorphic markers have allowed demonstration of
      strong genetic linkage between the type VII collagen locus and the dystrophic
      forms of EB (epidermolysis bullosa). This overview summarizes the progress made
      in the molecular genetics of type VII collagen.

PMID- 1344658
TI  - T-cell receptor gamma delta-positive peripheral T-cell lymphomas presenting in
      the skin: a clinical, histological and immunophenotypic study.
AB  - Examination of biopsy samples from 62 patients with--or with suspected--cutaneous
      T-cell lymphoma (CTCL) revealed 2 cases in which the neoplastic cells were
      positive for the T-cell receptor (TCR) gamma delta complex. One patient had
      mycosis fungoides and 1 patient had a pleomorphic lymphoma of medium and large
      cell type. Both cases showed aggressive courses with dissemination to internal
      organs and short survival times. The phenotypic examination showed that the
      neoplastic cells were positive with TCR delta 1, CD3, CD25, CD29, CD45R0 and
      CD54. No staining was seen with antibodies against framework determinants or
      variable regions on the TCR alpha beta heterodimer. Negative reactions were also
      seen with CD4, CD8, CD5, CD7, CD16, CD30 and CD57. It is concluded that rare CTCL
      express TCR gamma delta chains. These malignancies may originate from the TCR
      gamma delta-positive T cells seen in normal skin, and it is possible that their
      recognition may be important for clinical reasons.

PMID- 1344659
TI  - Heterogeneity of cytokine production by human malignant melanoma cells.
AB  - Recent investigations indicate that malignant melanoma cells can produce distinct
      cytokines. While differences in the production of single cytokines have been
      observed among different melanoma cell lines, the extent of variability in the
      production of single and multiple cytokines between individual melanoma cell
      lines has not been as thoroughly investigated. A heterogeneity in melanoma cell
      cytokine production could have important implications for the biology of this
      aggressive neoplasm since certain cytokines may act as autocrine growth factors
      or be potent modulators of host immune response to the developing tumor. The
      purpose of this study is to assess the cytokine production profile of two widely
      available human melanoma cell lines, A375 and G361. The A375 cell line
      constitutively expressed the mRNA for IL-1 alpha, IL-1 beta and PDGF-A, with
      increased expression of these cytokines after induction with PMA. GM-CSF mRNA was
      expressed by the A375 melanoma line only after induction with PMA. No IL-6 mRNA
      was detected in the A375 melanoma cell line. The cell culture supernatants from
      the A375 cells likewise contained a parallel increase in IL-1 activity as
      determined in the D10 bioassay and secreted GM-CSF and PDGF-AA as measured by
      ELISA. In contrast, the G361 cell line did not express IL-1, GM-CSF or PDGF-A
      mRNA (constitutively or after PMA induction) but expressed only IL-6 mRNA and
      secreted IL-6 activity after PMA induction. These results demonstrate a
      significant heterogeneity in the production of IL-1 alpha, IL-1 beta, IL-6, GM
      CSF, and PDGF in two distinct melanoma cell lines. This study demonstrates that
      individual melanoma cell lines express and secrete multiple cytokines both
      constitutively and after stimulation with PMA. The immunodulating and mitogenic
      properties of these melanoma-derived cytokines may have implications in
      determining the biologic behavior of different malignant melanomas.

PMID- 1344660
TI  - A reappraisal of the use of 5-methoxypsoralen in the therapy of psoriasis.
AB  - 5-methoxypsoralen (5-MOP) is considered an alternative to 8-methoxypsoralen (8
      MOP) for photochemotherapy of psoriasis. We have compared the clinical efficacy
      and tolerability of 5-MOP (1.2 mg/kg)-UVA versus 8-MOP (0.6 mg/kg)-UVA therapy in
      25 patients of skin type III and IV, affected by relapsing plaque-type psoriasis
      of similar body involvement; indeed, the same patients were given 8-MOP during 1
      year and 5-MOP during the subsequent year after relapsing. Both treatments
      cleared psoriatic lesions with a comparable number of exposures, but 5-MOP
      required significantly higher cumulative UVA doses. The difference was due to the
      lower phototoxicity of 5-MOP, as assessed by the determination of the minimal
      phototoxic dose, and to its higher tanning activity, as assessed by the weekly
      grading of pigmentation. Nevertheless, therapy by 5-MOP-UVA seemed particularly
      interesting in that it showed a higher tolerability since only 1 patient
      experienced nausea, whereas during therapy with 8-MOP-UVA nausea and/or vomiting
      occurred in 7 patients, sunburn in 6 and itching in 3. Since we have treated the
      same patients with the two drugs, our results were not influenced by
      interindividual variations of phototoxic responses, tanning ability and
      susceptibility to develop psoralen-induced short-term side-effects. It was
      concluded that, although long-term side-effects of the 5-MOP-UVA treatment have
      still to be determined, such treatment of psoriasis should be reappraised due to
      its higher tolerability in comparison to 8-MOP-UVA treatment.

PMID- 1344661
TI  - The 6/2 (AA3) polyclonal antibody identifying a 37 kD keratinocyte protein reacts
      also with BM-600/nicein, the basement membrane component bound by the monoclonal
      antibody GB3.
AB  - An unexpected finding concerning our previously reported polyclonal antibody
      raised against an extract from human amnion (pAb 6/2, also termed AA3), and which
      recognizes an epidermal keratinocyte protein, is presented in this study. Using
      the immunoblot technique, pAb 6/2 binds to a 37 kD intracellular protein antigen.
      We have subsequently found that, by radioimmunoprecipitation performed after
      metabolic labelling with 35S-methionine of cultured keratinocytes, pAb 6/2
      recognizes the 600 kD epidermal basement membrane component (termed BM
      600/nicein) which was reported to be bound by the monoclonal antibody mAb GB3.
      Specifically, pAb 6/2 reacts with immunoaffinity chromatography-isolated BM
      600/nicein blotted onto nitrocellulose. The data suggest the existence of two
      immunological reactivities borne by pAb 6/2, each of them being directed against,
      respectively, the 37 kD (seen in immunoblots) and the 600 kD protein (seen in
      immunoprecipitations). The data further suggest possible independent expression
      of these two proteins in cell culture. In comparison with the staining pattern of
      normal skin, immunofluorescence was previously noted to be impaired (pAb 6/2) or
      absent (mAb GB3) in lethal junctional epidermolysis bullosa. Thus, we conclude
      that mAb GB3, rather than pAb 6/2, is a more appropriate probe for the
      comprehensive biochemical study of this genodermatosis.

PMID- 1344663
TI  - Studies to define viral cofactors for human immunodeficiency virus.
AB  - Results from molecular biologic, cell biologic and animal experiments show that
      HIV replication can be driven by a variety of other viruses. If such interactions
      took place in vivo, then they could help to explain some of the complex
      pathogenesis of AIDS. The problems incurred in attempting to address this
      question in populations of humans are discussed.

PMID- 1344662
TI  - The role of interleukin-1 in host responses to infectious diseases.
AB  - The polypeptide cytokine interleukin-1 (IL-1) affects nearly every tissue and
      organ system. IL-1 is the prototype of the pro-inflammatory cytokines in that it
      induces the expression of a variety of genes and synthesis of several proteins
      which, in turn, induce acute and chronic inflammatory changes. Most studies on
      the biology of IL-1 have been carried out in animals, but human subjects have
      recently been injected with recombinant IL-1 and the results confirm IL-1 as
      being a mediator of disease as well as host defense. However, overproduction of
      IL-1 leads to debilitation of normal host functions; therefore, reduction of IL-1
      synthesis or blockade of IL-1 activity becomes a target of therapy in many
      diseases. Agents for reducing the synthesis or antagonizing the effects of IL-1
      have been sought, but the naturally occurring IL-1 receptor antagonist (IL-1Ra)
      has opened new experimental and clinical approaches. The ability of IL-1Ra to
      block IL-1 receptors without agonist activities has reduced the severity of
      diseases such as septic shock, lethal sepsis, inflammatory bowel disease,
      experimental arthritis, and the spontaneous proliferation of human leukemic
      cells.

PMID- 1344665
TI  - Risk of hepatitis B and human immunodeficiency virus transmission to a patient
      from an infected surgeon due to percutaneous injury during an invasive procedure:
      estimates based on a model.
AB  - The objective was to estimate the probability of sporadic hepatitis B virus (HBV)
      and human immunodeficiency virus (HIV) transmission to a patient from an infected
      surgeon due to percutaneous injury during an invasive procedure. Risk was
      estimated based on a model involving three probabilities: A, the probability that
      the surgeon will sustain a percutaneous injury during an invasive procedure; B,
      the probability that the sharp object causing the injury and now contaminated
      with the surgeon's blood will contact the patient's wound; and C, the probability
      that infection would be transmitted to the patient after such an exposure. The
      probability of transmission during one procedure is p = A x B x C. The
      probability of transmission to at least one patient during N procedures is 1-(1
      p)N. Values for A, B, and C were estimated from prospective studies. The
      estimated probability of transmission from an infected surgeon to a patient
      during a single procedure is 0.00024-0.0024% for HIV and 0.024-0.24% for HBV if
      the surgeon is positive for hepatitis B e antigen (HBeAg). The estimated
      probability of transmission to at least one patient during 3,500 procedures
      (estimated to be performed during an HIV-infected surgeon's remaining working
      life) is 0.81-8.1% for HIV; 57-100% for HBV if the surgeon is an HBeAg carrier.
      These estimates represent population averages and may not necessarily apply to a
      particular procedure performed by a particular surgeon, for which the risk may be
      considerably lower or higher than the estimated average. This risk assessment,
      which is based on limited data and does not take clusters of transmission into
      account, predicts that the risk of sporadic HBV transmission from infected
      surgeons to patients due to percutaneous injury during an invasive procedure is
      small and that the risk of HIV transmission is less than that for HBV. More data
      are needed to understand both sporadic and epidemic transmission in order to
      further reduce patient risk.

PMID- 1344664
TI  - Lipid transport in Plasmodium.
AB  - During intraerythrocytic development, the human malaria parasite Plasmodium
      falciparum actively internalizes phospholipids from its erythrocyte membrane and
      the extracellular medium. The import of exogenous lipids is not due to
      endocytosis, but to energy-dependent, transbilayer movement of phospholipids
      induced by the parasite in the erythrocyte surface. Novel tubular membranes that
      appear to emerge from the vacuole of the parasite and extend into the erythrocyte
      cytoplasm are labeled by exogenously added fluorescent lipids. These tubules
      interact with the erythrocyte membrane, but definitive evidence for their role in
      catalyzing transbilayer phospholipid movement in the red blood cell bilayer is
      still not available. Both biochemical and microscopic studies indicate that all
      lipid analogs internalized into the intraerythrocytic compartments and/or the
      parasite are not exported back to the host cell surface. Nonexchangeable
      fluorescent lipids are exported from a parasite to its intraerythrocytic tubules,
      but not to an adjacent parasite in a double-infected red blood cell. Thus, while
      the intraerythrocytic membranes engage in prominent tubular development at the
      vacuolar surface and deliver lipids to the parasite they originate from, they
      appear to be incapable of vesicular or tubular membrane export across the
      erythrocyte cytosol. Parasite Golgi activities for the synthesis and accumulation
      of sphingomyelin are detected in the intraerythrocytic tubules, indicating a
      novel export of classic secretory functions to their lumen, which could be
      central to both tubular development and lipid-sorting activities in these
      organelles.

PMID- 1344666
TI  - Prophylaxis and therapy for Pneumocystis pneumonia--where are we?
AB  - The armamentarium of drugs to treat and to prevent Pneumocystis pneumonia has
      expanded substantially over the past decade. In all patient populations
      trimethoprim-sulfamethoxazole is the preferred regimen for both acute treatment
      and prophylaxis. Clindamycin-primaquine and atovaquone are both effective agents
      for acute therapy but there are no data yet suggesting that they are preferable
      to trimethoprim-sulfamethoxazole. Corticosteroid therapy is now standard for
      severe AIDS-associated Pneumocystis pneumonia, and should probably be used in
      other patient populations with severe pneumocystis pneumonia as well.

PMID- 1344667
TI  - Challenge of Chlamydia research.
AB  - Chlamydia is an obligate intracellular bacterial pathogen that severely
      challenges the patience and creativity of all its investigators--even to the
      point that some investigators have forsaken this field for more productive and
      fertile areas of research. The two principal difficulties that touch every aspect
      of chlamydial research are (a) that chlamydiae only grow within eukaryotic host
      cells and (b) there are limited genetic approaches available. Despite these
      technical difficulties, the fundamental underlying problem has been the
      expectation that chlamydiae are similar to other bacteria (or, historically,
      viruses) and amenable to study from this perspective. However, this has often
      turned out not to be the case. Chlamydiae have shown themselves to be unique at
      many levels and thus represent a formidable, yet enticing, research challenge.

PMID- 1344668
TI  - Helicobacter pylori and gastroduodenal disease: pathogenesis and host-parasite
      interaction.
AB  - Helicobacter pylori has been shown to be the cause of chronic active gastritis
      and the evidence that it is involved in the development of peptic ulcer disease
      and gastric cancer is compelling. Narrow host range, tissue specificity, and
      chronic inflammation are hallmarks of infection. The study of virulence
      determinants has just begun but it seems likely that urease, adhesins,
      cytotoxins, and mediators of inflammation will prove to be important.

PMID- 1344669
TI  - Occurrence and mechanisms of glycopeptide resistance in gram-positive cocci.
AB  - Despite belief that the unique mechanism of glycopeptide action would preclude
      the development of resistance in susceptible organisms, clinical isolates of
      enterococci and staphylococci resistant to these compounds have been described.
      Among the enterococci, there are at least three types of resistance. Type A (high
      level) resistance was described in Enterococcus faecium and E. faecalis. It is
      inducible and mediated by elaboration and/or increased activity of at least three
      enzymes: a ligase, a dehydrogenase, and a carboxypeptidase, which orchestrate the
      production of peptidoglycan precursors that do not bind vancomycin. Type B (low
      level) resistance described in E. faecium is also mediated by increased
      carboxypeptidase activity and, possibly, by elaboration of a protein detectable
      after incubation in vancomycin whose function is unknown. Type C resistance is
      associated with production of a ligase constitutively produced, chromosomally
      encoded, and unique to E. gallinarum. Among the staphylococci, coagulase-negative
      clinical isolates were obtained that were resistant to glycopeptides and one
      coagulase-positive isolate was resistant to teicoplanin but the mechanism of
      resistance is unknown. Additionally, coagulase-positive staphylococci resistant
      to glycopeptides have been prepared in the laboratory. They produce an
      approximately 39-kDa cytoplasmic protein, whose function is unknown, and have
      undergone extensive reorganization of their cell surface. The era in which
      universal gram-positive susceptibility to glycopeptides can be presumed is over;
      susceptibility testing must now accompany isolation of an enterococcus or
      staphylococcus of clinical importance.

PMID- 1344670
TI  - Human papillomavirus, human immunodeficiency virus, and cervical cancer: newly
      recognized associations?
AB  - There are now sufficient data to conclude that women infected with human
      immunodeficiency virus (HIV) have an increased risk of human papillomavirus (HPV)
      infection and preinvasive stages of cervical cancer. This association is not
      completely due to immunosuppression. It is likely that HPV pathogenesis is
      altered in HIV-infected women. Preinvasive cervical neoplasia likely occurs more
      frequently in HIV-infected women because of several factors, including
      immunosuppression, viral interactions, and alterations in viral pathogenesis. As
      new treatments prolong the life of HIV-infected individuals, we must continue to
      be aware of and reactive to an increasing number of opportunistic complications
      of HIV infection, such as HPV infection and associated diseases.

PMID- 1344671
TI  - Virus research at the Princeton Rockefeller Institute, 1930-1945: recalling a
      wellspring of discoveries.

PMID- 1344672
TI  - Setting health-based residue limits for contaminants in pharmaceuticals and
      medical devices.
AB  - A procedure for determining health-based residue limits for impurities in drug
      substances and medical devices is described. The procedure is based upon the
      concept of setting residue limits that correspond to the intended usage of the
      drug or device, i.e., short-term use, prolonged use, and/or lifetime use. Data
      pertaining to chemical and physical properties, occurrence and use,
      biodisposition, pharmacology, toxicology, and effects in people are used. After
      evaluation of these data, acceptable daily intake (ADI) values are derived using
      a safety margin approach for short-term and prolonged exposure limits. The safety
      margin approach combines the use of safety factors and professional judgment. ADI
      values for lifetime exposure are calculated using the safety margin approach for
      noncarcinogens and for some carcinogens, and they are calculated using risk
      assessment procedures that provide ADI values corresponding to no more than a 1
      in 10,000 excess lifetime cancer risk based upon maximum likelihood risk levels
      for other carcinogens. A weight-of-evidence test determines the use of each
      approach. Finally, ADI values from relevant routes and endpoints are compared and
      a residue limit or residue limits are estimated. The standard is expressed in
      terms of maximum dose per exposure period and/or dose per day and is applicable
      to medical products intended for short-term use, for prolonged use, and/or for
      lifetime use as a major clinical indications dictate.

PMID- 1344673
TI  - Rational model for comparing vulnerability to environmental health risks at
      different locations.
AB  - Many factors must be considered in correlating the environmental quality of a
      location with the disease pattern. Therefore, an attempt is made to identify the
      rationale needed to correlate human disease patterns with pollutant loads and a
      simple, though arbitrary, and qualitative model for distinguishing areas more
      prone to environmental health risks is suggested.

PMID- 1344674
TI  - A discussion of the U.S. EPA methodology for determining Water Quality Standards
      (WQS).
AB  - Based on material published by the U.S. Environmental Protection Agency (U.S.
      EPA) in the Federal Register for 19 November 1991, many state environmental
      agencies have proposed and/or adopted revisions to their State Water Quality
      Standards (WQS) for organic and inorganic chemicals in fresh and marine waters
      (see, for example, State of Connecticut, Department of Environmental Protection,
      Bureau of Water Management, (1992), memorandum to Interested Parties concerning
      the Water Quality Standards Hearing Report). Generally, many states simply
      republish the U.S. EPA's proposed Water Quality Criteria (WQC) as the State's
      proposed WQS. Many of the state WQS and federal WQC values--especially those for
      organic compounds regulated as human or animal carcinogens--are much more
      stringent than the values now in effect because the U.S. EPA's new methodology
      (i) for estimating exposure point concentrations, exposure doses, carcinogenic
      potency, and incremental lifetime cancer risk and (ii) for setting the target
      acceptable risk combine a series of conservative assumptions into an equally
      conservative set of results. In the Federal Register proposal, the U.S. EPA
      failed to honor its standard risk assessment methodology in that (i) it failed to
      perform a quantitative or even qualitative uncertainty analysis and (ii) it
      failed to analyze the overall degree of conservatism in the results. The U.S. EPA
      suggested that the analysis is suitably conservative for the average exposed
      adult, but it failed to consider various phenomena that make the proposed WQC far
      more conservative than acknowledged or intended. To focus on a central problem of
      manageable size, this article dissects the method by which the U.S. EPA
      calculates proposed WQC for organic chemicals regulated as human or animal
      carcinogens. Because the results for most such chemicals are driven by the
      pathway for the human ingestion of fish which have bioconcentrated the chemicals
      from the water column (as opposed to the pathway for direct ingestion of water by
      humans), this article focuses exclusively on the fish-to-human pathway. These
      considerations form the basis of general quality assurance criteria and
      standards.

PMID- 1344675
TI  - Quality assessment of external data: a further means of reducing animal use for
      toxicity testing--a case study.
AB  - One overlooked area of quality assurance (QA) is the critical, in-depth
      reassessment of toxicity data from secondary compilations. Such retrospective QA
      may play a role in avoiding needless additional or repeated animal testing, as
      this case study shows. Initially, the task was simply to carry out toxicity
      testing of a chemical for LD50 determination for regulatory purposes. The impetus
      for this proposed (re-)testing was the erroneously calculated low LD50 value for
      just one species and one route of administration. Examination of the original
      literature cited as the source of the seemingly anomalous LD50 value revealed
      that a combination of conceptual and transcriptional errors had been made when
      the results were translated from the original German research paper and were put
      into two widely used secondary compilations: RTECS and HSDB. Correcting these
      errors rendered the true value for LD50, which was no longer out of step with
      values for other species, nor was it sufficiently low to cause any concern in the
      work place. The critical reassessment removed the need to use any further animal
      studies to assess the situation. It is concluded that, in some cases,
      "reassessing" existing data can be added to the established list of "refining,
      reducing, and replacing" as a means of decreasing animal use in toxicological
      evaluation.

PMID- 1344676
TI  - Application of ISO 9002 and FDA's good manufacturing practices to general
      chemical manufacturing.
AB  - Two manufacturing standards are discussed and compared, namely, the U.S. Food and
      Drug Administration's Good Manufacturing Practices and the International
      Standards Organization 9000 (ISO 9000) series. Conclusions are drawn relative to
      quality improvement strategies.

PMID- 1344677
TI  - A scientific basis for proposed quality assurance of a new screening method for
      tumor-like growths in the planarian, Dugesia dorotocephala.
AB  - Various abnormal growths appear on planarians, Dugesia dorotocephala, during and
      after exposure to polychlorinated biphenyls (PCBs) 28, 110, and 126; Aroclor
      1254; cadmium sulfate; and L-buthionine-(R,S)-sulfoximine (BSO). Daily
      observations under magnification were used to describe the location, development,
      and morphology of three different types of tumor-like growths ("tumors"). "Post
      head tumors" were found to be highly invasive, progressive, and lethal to the
      animal depending on concentrations and combinations of the compounds used.
      Survivors from post-head tumors exhibited aberrant morphogenesis, but
      developmental abnormalities were eventually shed. Post-head tumors occurred
      within 2 weeks of initial exposure, while "round tail tip tumors" appeared after
      2-3 weeks. The rate of progression and invasiveness was greater for the round
      tail tip tumors. "Pigmented rose thorn tail tumors" occurred in low incidence (4
      20%) and appeared to be harmless and noninvasive, requiring months to develop
      from the first appearance of pigmentation. The aggressive, proliferative, and
      invasive characteristics of post-head and round tail tip tumors are analogous to
      those of malignant tumors, while pigmented rose thorn tumors were benign. High
      dose of cadmium alone were sufficient to initiate the post-head and round tail
      tip tumors. PCBs potentiated the tumorigenicity of low cadmium doses and enhanced
      the very low spontaneous incidence of pigmented rose thorn tumors. PCBs also
      impaired motor activity, causing the graceful gliding locomotion to be replaced
      by a twisting serpentine movement accompanied by muscular dystrophy. In addition,
      high (50 micrograms) doses of PCB 110 depressed activity, while lower (5
      micrograms) doses and 50 micrograms Aroclor 1254 induced restlessness and
      enhanced locomotion. These data provide the basis for quality assurance.

PMID- 1344678
TI  - The inspection of drug metabolism and pharmacokinetic studies.
AB  - Areas in which the regulations apply must be discussed to ensure that an overall
      standard of "good practice" is applied to Absorption Distribution Metabolism
      Excretion (ADME) as an integral part of the safety testing program. There are
      specific problems in adapting the toxicology regulations for drug metabolism and
      pharmacokinetic studies. In reviewing the laboratories and their experimental
      procedures, an attempt to identify, through an auditing approach, how a drug
      metabolism laboratory can comply with regulations is presented. It must be
      regarded as of paramount importance that all work be carried out to the highest
      standards to allow the largest margin of safety. With these experiences, ADME
      Laboratories "new" to Good Laboratory Practice can proceed along the compliance
      pathway with minimum trauma to man, animal, and machine.

PMID- 1344679
TI  - Intellectual property issues in a clinical trial: a corporate perspective.

PMID- 1344680
TI  - [The estimation of the economic damages caused as a consequence of the epidemic
      of hemorrhagic dengue in Cuba in 1981].
AB  - In order to warn the health authorities in our region about the economic damages
      that a hemorrhagic dengue epidemic may cause, it was decided to study and publish
      the estimated cost of the Cuban epidemic in 1981, during which 344,203 diseased
      were reported, 10312 severe cases and 158 deceased. Economic costs include
      hospitalization expenses, assistance in emergency units, social security,
      expenses in out-patient treatment, goods not produced and expenses in the anti
      vector campaign. Probably, this epidemic which could be controlled in about 4
      months, has been the one causing most economic damages to date.

PMID- 1344681
TI  - [Mycobacterium fortuitum: the determination of its susceptibility by the disk
      diffusion technic].
AB  - A study was carried out on 40 Mycobacterium fortuitum strains isolated from 39
      symptomatic respiratory patients and 1 from a chronic skin ulcer, the
      susceptibility of whom to different antimicrobial agents was determined by the
      disk diffusion method. The strain showed sensitivity to aminoglucosides such as
      amikacin, gentamicin and kanamycin, and in all cases resistance to the
      penicillins ans cephalosporins used.

PMID- 1344682
TI  - [A comparison of 3 single-dose plans for mebendazole in the treatment of
      trichuriasis].
AB  - People infected by Trichuris trichiura were selected in a community by the Kato
      Katz technique. The study included a universe of 376 persons, male and female,
      positive and asymptomatic, monoparasitic and multiparasitic. They were divided in
      treatment groups with not less than 50 people. Monoparasitic patients were
      treated with 500, 400 and 300 mg of mebendazole, and multiparasitic patients with
      500 and 400 mg of mebendazole. In all the cases the drug was used in single doses
      and its administration was supervised by the physician. Therapeutical response in
      monoparasitic and multiparasitic patients is shown. It is suggested to use
      mebendazole single doses of 300 mg in monoparasitic and of 400 mg in
      multiparasitic patients with an intensiveness of less than 5,000 h/g, as an
      alternative for treating asymptomatic populations with T. trichiura.

PMID- 1344683
TI  - [The surveillance of nosocomial bacteremia in the Intensive Care Unit of the
      Hospital Pediatrico Docente Centro Habana].
AB  - A prospective study was carried out in order to assess nosocomial bacteremia in
      the Intensive Care Unit of the Centrohabana Teaching Pediatric Hospital, from
      January to May 1988. 66.7% of the bacteremia episodes diagnosed were of a
      nosocomial origin, mostly secondary. Nosocomial bacteremia rate was 15.5 per 100
      admissions, with predominance in the age group under 1 year of age. Risk factors
      for acquiring nosocomial bacteremia were hospital stay longer than 72 hours, age
      under 1 year, tracheal intubation, deep venous catheterization and urinary
      catheterization. The most frequently associated microorganisms were
      Staphylococcus epidermis, Escherichia coli and Pseudomonas aeruginosa.

PMID- 1344684
TI  - [The diagnosis of cryptococcosis. A comparison of 2 latex systems for antigen
      detection].
AB  - A latex reactive was designed for detecting Cryptococcus neoformans antigen. It
      was evaluated by a comparative study with a commercial system (Meridian
      Diagnostic, Inc.). Total coincidence was observed with both latex systems after
      studying 3 sample groups: patients with cryptococcosis diagnosis, blood bank
      donors and patients with clinical signs of the disease. Sensitivity, specificity
      and stability of the latex reactives prepared were assessed. This diagnostic
      technique opens new perspectives for quick diagnosis in Cuba, especially for
      immunosuppressed patients. It will allow for timely treatment and at the same
      time will contribute to saving expenses in imports.

PMID- 1344685
TI  - [The identification of Leptospira strains of different origins].
AB  - Leptospirosis is at present an ever-increasing problem in human and animal
      health. By means of the Korthof medium, 43 Leptospira strains were isolated from
      samples of human blood, water and soil. For their identification the
      microagglutination technique was used. The strains corresponded to the species
      Leptospira biflexa and Leptospira interrogans.

PMID- 1344686
TI  - [The evaluation of the epidemic risk for ARI by using a personal computer].

PMID- 1344687
TI  - [Pediatric AIDS: a report of the first fatal Cuban pediatric case].
AB  - The case of a Cuban child with AIDS acquired by perinatal transmission is
      reported. Thirteen days after birth, the child had chronic diarrhoeas affecting
      its pondostatural development. It was hospitalized many times due to recurrent
      respiratory processes, in one of which Pneumocystis carinii was detected. Oral
      candidiasis, cryptosporidiosis and intestinal amebiasis in faeces were also
      diagnosed. It died with generalized tonic-clonic convulsions and bradypnea. At
      autopsy, the direct death cause was endocranial hypertension due to unspecific
      sub-acute viral meningitis.

PMID- 1344688
TI  - [Infections and other opportunistic processes in a group of Cuban stage-IV HIV
      patients].
AB  - Forty Cuban patients affected by the human immunodeficiency virus (HIV),
      belonging to Group IV, assisted during a year at the Pedro Kouri Tropical
      Medicine Institute, are reported. Pneumocystis carinii, cryptosporidiosis,
      mucocutaneous herpes simplex, oral candidiasis and multidermatoma herpes zoster
      were the most commonly found infections. Other non-opportunistic diseases such as
      dermatitis seborrhoeica and onychomycosis were also present.

PMID- 1344689
TI  - [The study and evaluation of a method for identifying Escherichia coli by using
      fluorescent disks].
AB  - A study was carried out with 101 strains, 79 of Escherichia coli and 22 of other
      genera isolated from clinical samples at several hospitals in Havana form October
      1989 to January 1990. In all the strains, beta-glycuronidase enzyme was detected
      in conditions established by our laboratory and was compared with the results
      reached by the ROCHE enterotube method. Of the 79 Escherichia coli strains, 74
      were positive to the beta-glycuronidase detection test. Sensitivity was 94% and
      specificity, was 100%.

PMID- 1344690
TI  - [A structural protein study of the influenza A (H1N1) virus by polyacrylamide gel
      electrophoresis].
AB  - Influenza is an acute respiratory disease typically appearing as an epidemic.
      Three immunological types of the influenza virus are known: A, B and C.
      Continually, antigen changes occur, especially in type A. Therefore, a
      comparative study was carried out on 4 influenza A(H1N1) virus strains in
      relation to protein structure (surface antigens), by using polyacrylamide gel
      electrophoresis by the modified Laemmli method. The objective was to compare the
      structural proteins of the A/Havana/1292/78 (H1N1) national strain with the
      proteins of 3 international pattern strains. In all the cases, 6 bands were
      detected by densitometry. In the 4 strains studied the most abundant protein was
      M. Great differences between the Cuban strain and the 3 international patterns
      were not seen.

PMID- 1344691
TI  - [Malaria and sickle-cell anemia. A correlation of the clinical and
      epidemiological aspects].
AB  - A study was carried out on susceptibility of sicklemia patients to Plasmodium
      falciparum (PF) malaria in 151 hemoglobin S carriers (homozygous and
      heterozygous), assisted at the Cotonu Hospital, Benin, for 1 year. These diseased
      did not have any serious malaria complications. The results were compared to a
      control group without sickle-cell anemia who had 21.5% of complications due to
      the disease. Prevalence of genetic anomaly was higher than 20% among the general
      population under study.

PMID- 1344692
TI  - [A preliminary study of variation in Tarebia granifera (Lamarck), Rio Hatibonico,
      Camaguey].
AB  - A study was carried out on Tarebia granifera in Camaguey which allowed to gather
      ecological evidence in order to know this freshwater mollusk species likely to
      act as a biological control agent of intermediate hosts for tropical diseases.
      Highest density was observed in November, coinciding with the highest
      temperatures of a running water habitat. Also, there was an influence of density
      variations according to variations of ions NH4+, NO2- and NO3- concentrations in
      the medium. These data are useful to know the right time for extracting Tarebia
      granifera from the habitat and using it as competitor without considerable
      alterations in the population stability.

PMID- 1344693
TI  - [Rotavirus diarrhea in a health center and a hospital of Managua, Nicaragua].
AB  - Diarrhoea has been considered by WHO as a major problem of morbidity and
      mortality in children under 5 years. Rotavirus has been reported as one of the
      main causal agents, although its frequency as causal agent of diarrhoea in
      Nicaragua is not known. A study was carried out on 206 samples from an equal
      number of children under 5 years, who presented at a health center and a
      pediatric hospital in Managua during 9 months in 1987. In order to detect the
      presence of Rotavirus in faeces, the ELISA technique was used. It was proved that
      Rotavirus is not a significant cause of diarrhoea in children under 5 years in
      the places studied.

PMID- 1344694
TI  - Contrast sensitivity in clinical practice.
AB  - We collected and evaluated the results of contrast sensitivity (CS) examination
      by means of Vistech chart with an arranged testing distance 208 and 420 cm
      covering spatial frequences 1.15-27.25 cycles/degree (c/deg). Our test was
      comprised of normal population and patients with chronic renal insufficiency
      including the group of waiting patients, dialysed patients and dialysed patients
      after neuroretinopathy and also patients after kidney transplantation and those
      with Alport's syndrome. We gave our attention to the results of visual acuity
      (VA) and contrast sensitivity (CS) examination in patients after surgery for
      detached retina, aphakic patients and patients with artephakia. We examined and
      evaluated CS in patients with intraocular hypertension. All patients reached the
      VA values 6/9-6/6. 1. The results of examination of 100 healthy persons of
      different age displayed significant differences in age groups covering all
      spatial frequencies between the groups 21-50, 51-60 and 61-80 years whereas in
      sets of higher age we registered differences in the region of medial spatial
      frequencies only. These data served us to create control groups in the individual
      partial groups. 2. Patients with chronic renal insufficiency have CS
      significantly lowered. These examinations suggest that there is a certain
      relation between renal and retinal functions and that the dialysation treatment
      is not able as yet to compensate fully all changes evoked by renal insufficiency.
      A clear tendency to normalize CS after renal transplantation is suggestive of a
      certain reversibility of these changes. This valid for transplant patients with a
      clear lens. If opacity of the posterior cortex of the lens occurs after a long
      time cortisone treatment, a substantial fall in the CS curve is registered in all
      spatial frequencies in spite of the VA being 6/9-6/6. Patients with
      neurotinopathy have CS always significantly disturbed. These changes are
      reversible although this reversibility is not complete. The new way of
      dialysation treatment secures a relatively rapid normalisation of pathological
      changes in the fundus and repair of subjective functions. At the same time we
      came to the conclusion that the prognostic outlooks of these patients have become
      distinctly better as far as their subjective visual functions are concerned. 3.
      Patients after surgery for detached retina displayed in all cases in the operated
      eye highly reduced CS in median and low spatial frequencies simultaneously with a
      statistically significantly lower threshold visual acuity and reduced slope of
      the acuity function in the diseased eye.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1344695
TI  - Our experience with management of epiphyseolysis in children and adolescents.
AB  - A total of 58 children is referred to with fractured growth plates of the distal
      forearm, proximal humerus, radial condyle of humerus, ulnar epicondyle of
      humerus, distal tibia, proximal tibia and the distal femur. The related injuries
      are divided in accord with Salter-Harris classification. The treatment of
      epiphysiolyses is concerned together with summarizing its results and the
      appropriate experience. In addition, the indications for both conservative and
      surgical approaches are delimited in treating these injuries.

PMID- 1344696
TI  - Surgical treatment of vesico-renal reflux in children aged up to 3 years.
AB  - A total of 36 children age-ranged from 2 up to 34 mos (17 boys and 19 girls) with
      previous surgery for the vesico-renal reflux has been evaluated. This disorder
      had most commonly been classified to be of higher degree (IV. and V.--45%) and
      often showed no response on repeated conservative treatment with even stronger
      antibiotics. The boys (27 ureters) and girls (31 ureters) underwent the 32
      antireflux operations after Anderson-Glenn and those 26 after Politano
      Leadbetter, respectively. In 6 ureters, their resection and modelling after
      Hendren was necessary to be done. On post-operative check-out, the 6 post
      antireflux Anderson-Glenn's plastic ureters revealed on miction cystography the
      persistent vesico-renal reflux re-operated subsequently in accord with Politano
      Leadbetter. From them, in 2 ureters the post-operative stricture has occurred in
      the site of ureter-to-bladder healing that was transitorily secured with
      percutaneous nephrostomy.

PMID- 1344697
TI  - Reconstruction of the penis following necrosis from circumcision used high
      frequency cutting current.
AB  - Penis necrosis secondary to circumcision by an electrical scalpel in a 2 years
      and 2 months-old boy occurred. After healing of the electric burn only stumps of
      the erectile bodies and strictured urethral meatus remained. The penis shaft
      reconstruction by corpora mobilisation and by detachment of the crura from the
      pubo-ischial rami was effected. This procedure gained 6 cm of a new length of the
      penis. To prevent readhesions to the puboischial rami the penis was buried in a
      scrotal tunnel. Six months later the denuded shaft was resurfaced with one split
      thickness skin graft and a zigzag seam on the ventral side was made. The patient
      voids with good stream, has spontaneous erections and nocturnal emissions. During
      10-years follow-up after the reconstruction two complications, namely a stricture
      of the urethra and a slight dorsal tethering of the penis caused by a scarred
      pubic skin were treated. The problems of the a reconstruction type and
      resurfacing of the penis in childhood are discussed.

PMID- 1344698
TI  - Advances of the past decade in automated hematology.
AB  - During the decade of the 1980s, a wealth of information accumulated concerning
      automation in hematology. Recent technological advances led the way to the
      development of blood cell analyzers capable of performing a ten-parameter (or
      greater) complete blood count and five-parameter (or greater) differential
      leukocyte count on a small amount of whole blood and in an accurate, efficient,
      and economical way. The authors summarize the available information concerning
      the data generated by these analyzers, the mechanisms involved in the data
      generation, and the clinical applications and usefulness or limitations of the so
      called new complete blood count parameters and of the automated differential as
      it compares with the manual differential.

PMID- 1344699
TI  - Automation in blood banking. Machines for clumping, sticking, and gelling.
AB  - Hospital transfusion services and blood donor centers have continued to rely on
      manual hemagglutination methods for pretransfusion compatibility testing.
      Automation with continuous flow and batch analyzers has been practical only for
      the largest donor centers. During the last 20 years, other methods of
      streamlining compatibility testing have evolved. Two of the most successful
      approaches have used microplates to perform liquid agglutination tests or solid
      phase, red cell adherence tests. More recently, a gel test has been developed. On
      the basis of these technologies, increasing numbers of semiautomated systems for
      compatibility testing have become commercially available. However, these systems
      primarily address the needs of large donor centers. New technologies are needed
      to automate the transfusion services of hospitals and other small laboratories.

PMID- 1344700
TI  - Automation in clinical microbiology.
AB  - Automation was introduced into the clinical microbiology laboratory in the 1960s
      but initially met with limited success. Today, instruments are an integral part
      of many clinical laboratories and are used for microbial detection,
      identification, and susceptibility testing; detection of positive blood cultures;
      screening urine samples for potential pathogens; and assaying levels of
      antimicrobial agents in body fluids. Automation has allowed more rapid diagnosis
      and elimination of the subjective interpretation of many manual tests. In
      addition, in some cases, automated tests are more sensitive and specific than
      manual techniques. However, automated testing often is more expensive than manual
      testing and is associated with the possibility of mechanical failure. Automation
      will continue to be an important part of the clinical microbiology laboratory and
      in the future will include more molecular biology technologies, such as the
      polymerase chain reaction. Perhaps practical applications of flow cytometry will
      be identified.

PMID- 1344701
TI  - Laboratory automation systems. An introduction to concepts and terminology.
AB  - The concept of laboratory automation has existed for years; such automation has
      been used primarily in nonclinical and industrial settings. The next step is to
      implement automation systems in the clinical laboratory. A laboratory automation
      system consists of robots, conveyor systems, machine vision, and computer
      hardware and software. Specimen movement and result reporting are based on the
      identification of specimens using bar coded specimens and bar coded specimen
      carriers. The implementation of a laboratory automation system is dependent on
      the presence of a laboratory information system. An interface between the
      laboratory information system and the laboratory automation system provides the
      information required to move the specimen through the laboratory. The reporting
      of results is dependent on the laboratory information system or manual input,
      depending on the type of work cell in which the results are produced. The
      greatest hurdle to overcome in developing and implementing a laboratory
      automation system is the integration of systems, including commercial laboratory
      instrumentation and user-defined work cells. The barriers to implementation
      primarily are proprietary in nature: instrument software and instrument hardware.
      When the instrument manufacturers realize the necessity for development of
      electronic and physical integration, the proliferation of laboratory automation
      systems will occur. Several opportunities exist for the reduction in laboratory
      expenses and the development of new positions, such as "robotechnologist," a
      staff member who would function in a manner similar to the current laboratory
      information systems manager. This article describes the author's concepts of
      laboratory automation.

PMID- 1344702
TI  - Automation and other recent developments in clinical chemistry.
AB  - The decade 1980 to 1990 was the most progressive period in the short, but
      turbulent, history of clinical chemistry. New techniques and the instrumentation
      needed to perform assays have opened a chemical Pandora's box. Multichannel
      analyzers, the base spectrophotometric key to automated laboratories, have become
      almost perfect. The extended use of the antigen-monoclonal antibody reaction with
      increasing sensitive labels has extended analyte detection routinely into the
      picomole/liter range. Devices that aid the automation of serum processing and
      distribution of specimens are emerging. Laboratory computerization has
      significantly matured, permitting better integration of laboratory instruments,
      improving communication between laboratory personnel and the patient's physician,
      and facilitating the use of expert systems and robotics in the chemistry
      laboratory.

PMID- 1344703
TI  - Automated immunohistochemical analysis.
AB  - As the demand for immunohistochemical tests (IHC) extends beyond artistry to more
      widespread medical diagnostic need, the field requires improvements in quality,
      reproducibility, speed, and standardization. Automated IHC offers the opportunity
      to impart new levels of quality, reproducibility, and standardization while
      reducing labor and reagent costs. In addition, the controlled environment of
      automated IHC may increase the speed and timeliness of results. Described is a
      computerized bar code-driven automatic immunostaining device that automatically
      dispenses reagents, controls washing, mixing, and heating to optimize IHC
      reaction kinetics, allowing assay within 60 minutes. This electronically
      controlled device generates high-quality, reproducible IHC assays in a medically
      timely manner.

PMID- 1344704
TI  - Automation of in situ hybridization.
AB  - The authors used automated DNA hybridization equipment, the Code-On
      (Instrumentation Laboratory, Lexington, MA), for more than 2 years to perform in
      situ hybridization in the clinical and research laboratory. For in situ
      hybridization for viral DNA in fixed, paraffin-embedded tissue, the Code-On
      produces results that are as sensitive as the manual method and with considerably
      greater ease. The procedure must be modified to fit the operating characteristics
      of the Code-On. The authors outline a procedure that emphasizes sensitivity,
      rather than speed. The automated procedure requires close technical attention,
      but the authors propose that it is considerably more efficient than the manual
      method. One technician can produce reliable results on as many as 60 slides a
      day. For in situ hybridization on cytogenetic preparations, the results are
      excellent, but the procedure is contorted and the probe use is increased. For
      these reasons the Code-On is not used for routine interphase cytogenetics. The
      Code-On is in routine use in the authors' pathology laboratory for performing in
      situ hybridization on formalin, B5, and Carnoy's fixed, paraffin-embedded
      specimens.

PMID- 1344705
TI  - Automation in cytopathology.
AB  - Machine-aided screening of cervical Papanicolaou (Pap) smears is being pursued in
      response to a cytotechnologist shortage and a perception that computer-aided
      screening may improve human screening. Several different commercial efforts are
      underway to automate either the processing of cervical specimens or the screening
      of Pap smears and nongynecologic specimens. The technical approaches used by
      these manufacturers are varied and include traditional algorithmic computers,
      expert systems, and neural networks, alone or in combination. Alternatives to
      cell smears on glass slides are also being studied, in which monolayer cell
      preparations facilitate the analysis of the cells. It is not possible to suggest
      what approach to automation in cytology is preferred at this time. Preliminary
      studies of different systems suggest several of them may have sensitivity to
      detect intraepithelial abnormalities in excess of 95%. It is likely that these
      technologies will significantly aid the analysis of cytologic specimens.

PMID- 1344706
TI  - Guidelines for transesophageal echocardiography in children.

PMID- 1344707
TI  - Clinical application of two computerized diabetes management systems: comparison
      with the log-book method.
AB  - In two consecutive studies the clinical application and suitability of two
      computer-assisted data management systems (Camit and Cadmo) were evaluated in a
      prospective manner. In each study nineteen long-standing, stable insulin
      dependent patients were randomly assigned to one of two groups. In study I
      assessment of metabolic control and insulin dose adjustments were based either on
      the Camit S1 data analysis or on the conventional log-book method, whereas in
      study II the Camit S2 and the Cadmo simulation programs were evaluated. HbA1c
      values decreased significantly in both studies (p < 0.05). A clear decline in
      hypoglycemic events as well as a significant reduction of the percentage of
      glucose values below 4.0 mmol/l (p < 0.005) and a marked increase (p < 0.05) in
      the percentage of glucose levels in the target range (4.0-10.0 mmol/l) were
      observed. We found both computerized assessment systems to be reliable and
      suitable for the assessment of blood glucose control and for insulin dose
      finding. The graphical and statistical presentation of the numerous glucose and
      insulin data allowed a better summary of blood glucose control and metabolic
      trends. More time could be spent for problem solving, which proved to be much
      less exhausting with the computer for the attending physician. Further studies
      should address the educational potential of computerized systems for the patient
      as well as for the physician.

PMID- 1344708
TI  - Dual publication of abstracts.

PMID- 1344709
TI  - Viral glycoprotein heterogeneity-enhancement of functional diversity.
AB  - Variations in the amino acid sequence of RNA virus envelope glycoproteins can
      cause changes in their antigenicity and can alter the host-cell tropism of the
      virus and the degree of virulence which it exhibits. Such changes may alter the
      course and outcome of viral diseases, either directly because of changes in the
      biological properties of the glycoproteins or indirectly through effects on
      immune surveillance and vaccine efficacy. The nature and extent of glycosylation
      of the surface glycoproteins of RNA viruses have also been implicated in such
      phenotypic alterations. It follows therefore that the 'plasticity' of the viral
      genome and the host-encoded glycosylation machinery combine to create populations
      of highly diverse viruses. This diversity is considered to be responsible for
      survival of these viruses in a variety of biological niches and for their ability
      to overcome the inhibitory effects of neutralizing antibodies and antiviral
      agents. In this article we discuss the implications of the inter-relationship
      between these two mechanisms for the generation of diversity.

PMID- 1344710
TI  - Preparation of N-acetylneuraminic acid from delipidated egg yolk.
AB  - Egg yolk, a large proportion of the egg, was studied for the preparation of N
      acetylneuraminic acid (Neu5Ac). The delipidated hen egg yolk (DEY; 500 kg
      containing 0.2% w/w, Neu5Ac) was hydrolysed with HCl (pH 1.4) at 80 degrees C and
      neutralized with NaOH (pH 6.0). The mixture was filtered and electrodialysed
      until the conductivity was 240 microS cm-1. The filtrate was applied on a column
      of Dowex HCR-W2 (20-50 mesh), followed by a column of Dowex 1-X8 (200-400 mesh).
      The latter column was washed with water, and then eluted with a linear gradient
      of HCO2H (0-2 M). The eluates containing Neu5Ac were concentrated using a reverse
      osmosis membrane and, finally, rotary evaporated at 40 degrees C. The residue was
      then lyophilized to yield 500 g Neu5Ac. The purity of Neu5Ac was > 98% (TBA
      method). HPLC, NMR spectroscopy and TLC chromatography of the product obtained
      from the DEY showed that Neu5Ac was the sole derivative present in egg yolk. The
      DEY, a byproduct from egg processing plants, was found to be an excellent source
      for the large-scale preparation of Neu5Ac.

PMID- 1344711
TI  - O-glycosidically linked oligosaccharides from peptidorhamnomannans of Sporothrix
      schenckii.
AB  - beta-Elimination of peptidorhamnomannans purified from yeast-like and mycelial
      phases of Sporothrix schenckii released neutral and acidic reduced
      oligosaccharides that were O linked to serine and/or threonine. Man-(alpha 1
      2)Man-ol, Rha(alpha 1-3)Man(alpha 1-2)Man-ol, Rha(alpha 1-4)GlcA(alpha 1
      2)Man(alpha 1-2)Man-ol, and Rha(alpha 1-4)[Rha(alpha 1-2)] GlcA(alpha 1
      2)Man(alpha 1-2)Man-ol were characterized based on methylation analysis, proton
      magnetic resonance and fast atom bombardment mass spectrometry.

PMID- 1344712
TI  - Alpha 1-6(alpha 1-3)-difucosylation of the asparagine-bound N-acetylglucosamine
      in honeybee venom phospholipase A2.
AB  - Chymotryptic glycopeptides were prepared from a honeybee (Apis mellifica) venom
      phospholipase A2 (E.C. 3.1.1.4) fraction, with high affinity towards lentil (Lens
      culinaris) lectin. Treatment of the glycopeptide mixture with peptide-N4-(N
      acetyl-beta-glucosaminyl)asparagine amidase A, followed by HPLC fractionation,
      yielded two oligosaccharides, which were analysed by 500 MHz 1H-NMR spectroscopy
      to give the following structures [formula: see text] This is the first report on
      a naturally occurring glycoprotein N-glycan with two fucose residues linked to
      the asparagine-bound N-acetylglucosamine.

PMID- 1344713
TI  - Separation and analysis of the glycoform populations of ribonuclease B using
      capillary electrophoresis.
AB  - The development of methods to separate, analyse and monitor changes in glycoform
      populations is essential if a more detailed understanding of the structure,
      function and processing of glycoproteins is to emerge. In this study, intact
      ribonuclease B was resolved by borate capillary electrophoresis into five
      populations according to the particular oligomannose structure associated with
      each glycoform. The relative proportions of these populations are correlated with
      the percentages obtained indirectly by analysis of the hydrazine released
      oligosaccharides using Bio-Gel P-4 gel filtration, matrix assisted laser
      desorption mass spectrometry and high performance anion exchange chromatography.
      Alterations in the composition of the glycoform populations during digestion of
      ribonuclease B with A. saitoi alpha(1-2)mannosidase were monitored by capillary
      electrophoresis (CE). Digestion of the free oligosaccharides under the same
      conditions, monitored by anion exchange chromatography, revealed a difference in
      rate, allowing some insight into the role of the protein during oligosaccharide
      processing. In conjunction with other methods, this novel application of CE may
      prove a useful addition to the techniques available for the study of glycoform
      populations.

PMID- 1344714
TI  - Alpha-D-galactosylation of surface fucoglycoconjugate(s) upon
      stimulation/activation of murine peritoneal macrophages.
AB  - Murine resident macrophages express, on their surface, carbohydrate epitopes
      which undergo changes during their stimulation/activation as monitored by binding
      of 125I labelled Evonymus europaea and Griffonia simplicifolia I-B4 lectins.
      Treatment of the stimulated macrophages with coffee bean alpha-galactosidase
      abolished binding of the GS I-B4 isolectin and changed the binding pattern of the
      Evonymus lectin. The affinity (Ka) of Evonymus lectin for alpha-galactosidase
      treated macrophages decreased approximately 23-fold, from 1.25 x 10(8) M-1 to 5.5
      x 10(6) M-1. Subsequent digestion of alpha-galactosidase-treated macrophages with
      alpha-L-fucosidase from Trichomonas foetus, further reduced binding of Evonymus
      lectin. Resident macrophages showed the same pattern of Evonymus lectin binding,
      with the same affinity, as alpha-galactosidase-treated, stimulated macrophages.
      These results, together with a consideration of the carbohydrate binding
      specificity of the Evonymus lectin which, in the absence of alpha-D-galactosyl
      groups, requires alpha-L-fucosyl groups for binding, indicate the presence, on
      resident macrophages, of glycoconjugates with terminal alpha-L-fucosyl residues.
      It is also concluded that during macrophage stimulation/activation alpha-D
      galactosyl residues are added to this glycoconjugate and that they form part of
      the receptor for Evonymus lectin. The same glycoconjugate(s) is/are also
      expressed on the activated macrophage IC-21 cell line which exhibits the same
      characteristics as that of stimulated peritoneal macrophages, i.e., it contains
      alpha-D-galactosyl end groups and is resistant to the action of trypsin. Both
      lectins were also specifically bound to Corynaebacterium parvum activated
      macrophages.

PMID- 1344716
TI  - Developmental screening of Afro-American infants using the Wolanski Gross Motor
      Evaluation.
AB  - The purpose of this study was to assess the appropriateness of using the Wolanski
      Gross Motor Evaluation (WGME) to screen for development delay in Afro-American
      infants of low socioeconomic status. Screening of 122 Afro-American infants at
      the Jefferson County (Alabama, USA) Department of Health well-child clinics was
      performed using the WGME. No differences were noted in the performance scores of
      males and females. The Afro-American infants of low socioeconomic status received
      higher performance scores at each given age than did white, middle-class U.S.
      infants tested in another study. The Afro-American infants also scored higher at
      each given age than the Polish infants on whom the WGME norms were established.
      The WGME does seem to be an appropriate screening tool in terms of practicality
      and the items are appropriate prior to onset of walking for the population
      studied. Normative data on different populations is needed in developing grids
      that can be used appropriately. Further studies are needed to establish
      reliability and validity.

PMID- 1344715
TI  - Monoclonal antibody GOM-2 binds to blood group B-Le(y) active glycolipid antigens
      on human gastric cancer cells, KATO-III.
AB  - The antigen structure of a mouse monoclonal antibody, GOM-2, established by
      immunization with KATO-III human gastric cancer cells, was examined. GOM-2
      reactive glycolipids were prepared from KATO-III cells and treated with
      endoglycoceramidase. Structural studies of ten GOM-2 reactive oligosaccharides by
      a combination of glycosidase digestions, methylation, and affinity chromatography
      on an Ulex europeus agglutinin I (UEA-I) column revealed that nine of them had a
      Y-related B-active difucosylated determinant (B-Le(y)) and one had a B-active
      determinant. Affinity chromatography of the purified and modified
      oligosaccharides on an immobilized GOM-2 column demonstrated that GOM-2 has a
      novel binding specificity: it binds tightly to the biantennary structure carrying
      the B-Le(y) determinant at the termini or the branched structure carrying the B
      Le(y) structure at two nonreducing termini.

PMID- 1344717
TI  - Gross motor skills in Navajo American Indian children one year or under.
AB  - The purpose of this study was to gather information on the appropriateness of
      using the Wolanski Gross Motor Evaluation (WGME) with a Navajo population. Eighty
      normal healthy Navajo children (41 boys, 39 girls) were tested within 7 days of
      4,6,9 and 12 months of age at Well Baby Clinics on the Navajo Indian Reservation.
      Total scores on the WGME were calculated for each age group. The scores of the
      Navajo boys and girls at each age were compared using a one-tailed Wilcoxon Rank
      Sum Test, a = .05, to look for gender-related differences at each age. No
      significant gender-related differences were found. The scores of the Navajo
      infants did not correspond with the existing WGME grids. Navajo infants appeared
      to score substantially higher than the Polish sample at 4 months. At six months
      the mean scores of Navajo infants fell just above the 95th %ile on the existing
      WGME grids but scores below the mean fell within the grids. At 9 and 12 months
      the of Navajo infants fell between the 15th and 65th %iles on the infants grids.
      These results indicate that normative data on the WGME would need to be gathered
      on Navajo infants before the test could be used for screening with that
      population.

PMID- 1344718
TI  - Shaping of functional and morphological asymmetry in five to thirty months old
      children.
AB  - Studies of 175 children in Katowice day nurseries were conducted. Functional
      differentiation of hands was determined by means of tests worked out by Franus,
      Spionek and Szuman. Morphological asymmetry was pronounced as based on the
      greatest value of arm circumference, the width of arm epiphysis, stylion width
      and hand thickness. Somatic indices, as well as asymmetry index according to
      Wolanski were defined on the basis of values achieved. The analysis of data shows
      that the degree of upper limb lateralization increases along with age. Temporary
      decrease of the number of lateralized individuals--and coincident increase of
      bimanual ones--was observed in girls at the age of 21-25 months, as well as in 25
      30 months old boys. Right--handedness is most commonly accompanied--though not on
      statistically significant level--by domination of the following right limb
      traits: the biggest arm circumference, the smallest forearm circumference and
      hand thickness.

PMID- 1344719
TI  - Socio-economic conditions of the family and somatic and physiological properties
      of parents and offspring.
AB  - This paper discusses problems related to the formation of the somatic and
      physiological traits of the human body seen against a social and economic
      background. Source material for the study was collected upon the examination in
      1975-1982 of a group of 1,108 families (altogether 3,830 persons including 1,756
      men) from urban, rural and industrial areas of Poland. Their biological status
      was described by fourteen somatic and nineteen physiological traits. Social
      standing and material well-being were defined by four factors: culture, living
      conditions, genetic factor of mother and the same factor of father. These formed
      the criteria for a division of the families into sixteen types. It was only
      within such sub-groups that biological development of individual family members
      was assessed. In every type of family and in every one of its members we can
      distinguish positively and negatively developed traits. In couples where both
      spouses were tall, the biological development of the majority of traits was
      rather satisfactory. In the cases where husband and wife differed in stature
      (mother taller than father in categories specific for each sex), then blood
      properties of offspring had higher values than in the reverse type of mating.
      Analysis of traits unrelated to body height showed fathers more sensitive to
      family environment factors than mothers, while their offspring showed a much
      weaker sensitivity than either parent.

PMID- 1344720
TI  - Health status of rural schoolchildren from Byelorussian Polesye: twenty-years
      shifts.
AB  - The complex research of children from Byelorussian Polesye has been making by
      author for last 20 years in the three studies: 1966-68, 1976-78, and 1986. The
      third one was carried out after the Chernobyl accident in South Byelorussia
      regions with high level of fall-out contamination. The acceleration of physical
      growth was established to continue for whole this period. The third study showed
      evidence of the impairment of immunological resistance and high predisposition to
      infection and inflammatory disease. It revealed in decrease of leucocytes and
      lymphocytes count and increase of monocytes and stab/band neutrophiles in
      comparison with the previous two studies. These results should be useful for
      monitoring of the population.

PMID- 1344721
TI  - Biological status of Jastarnia, Szczawnica and Kroscienko populations as an
      effect of adaptation to seaside and low mountain conditions.
AB  - The material consists of the families from Kroscienko and Szczawnica examined in
      1983 (309 men and 256 women) and of the families from Jastarnia examined in 1987
      (163 men and 192 women). In addition to 43 biological traits (somatic,
      physiological, and psychomotor), also socio-economic conditions of families were
      analyzed, along with basic demographic data for the study areas. It has been
      found that migrations of people and marital radius were higher in Jastarnia than
      in Pieniny, and at the same time infant mortality was higher in Jastarnia,
      although living conditions were better there (more rooms and more opportunities
      for additional income). Children and youth of both areas were characterized by a
      medium-strong body build. Stature, body weight, and adipose tissue were higher in
      Jastarnia than in Pieniny. Moreover, the inhabitants of Pieniny were europrosopus
      and hyperbrachycephalic, whereas the inhabitants of the seaside areas were
      leptoprosopic and brachycephalic. The vascular-respiratory system of the seaside
      population was characterized by lower mean hemoglobin concentrations and
      hematocrit index as compared with those in the low-mountain population. Most of
      the respiratory traits (VC, Ap, VE, MVV, FEV1), however, were higher in
      Jastarnia, only the frequency of respiration (f) being higher in Pieniny. A
      comparison of psychomotor traits showed no difference in the static strength and
      muscular explosive power between the two populations, but agility traits were
      higher in Jastarnia, whereas the body balance and musculatory endurance were
      better in the Pieniny population.

PMID- 1344722
TI  - Changes in biological status of the Jastarnia population over the last 20-year
      period.
AB  - The objective of this paper is to analyze changes in the biological condition of
      the inhabitants of Jastarnia (Hel Peninsula), who were examined three times
      during 1963-87. A total of 1791 persons of both sexes, aged from 3 to 80 years
      were under study. A total of 20 somatic and physiological traits were considered.
      According to the data of the Central Statistical Office (available from 1976) the
      birth rate in Jastarnia increased in 1987 but mortality increased even at a
      higher rate so that the increase of the population (per 1000 inhabitants) was
      reduced from 6.8 in 1976 to 3.7 in 1987. A factor analysis, used to estimate
      socio-economic conditions of two generations of this town, has shown that the
      apartment size and income of a family (factor 1) explained the highest percentage
      of the variance of the traits considered. Education of parents was on the second
      position (factor 2). The next factor (3) represented biological properties of
      parents measured by their stature. The last one (factor 4) characterized family
      size in the second generation, for the first generation this trait being related
      with factor 2 (culture). A tendency to slim body was observed in children and
      youth. However, the ratio of chest circumference to stature (Marty index) did not
      change, which can be explained in terms of the adaptation to maritime climate.
      The content of adipose tissue increased in children and youth, and also the vital
      capacity of lungs in relation to stature (Ziemssen index) increased in children.
      Blood pressure at rest was reduced in 1987, but systolic blood pressure at work
      was increased. An increase in the minute respiration rate and reduction of chest
      extension in the contemporary youth seem to be rather unfavorable.

PMID- 1344723
TI  - Regression of body build and motor fitness in 7-19-year-old Polish youth on
      energy use and demographic properties of regions.
AB  - A total of 65487 girls and 62002 boys aged from 7 to 19 years were examined in
      towns and villages all over Poland. Coefficients of multiple regression and
      percentage of explained variation in body build and motor fitness (somatic
      fitness traits) of youth were calculated in relation to the variation in economic
      activity (as measured by electric energy use) and in demographic properties of 98
      regions of Poland (urban and rural areas of 49 provinces separately).
      Calculations were made separately for girls 7-8, 9-10, 14-15, and 18-19 years old
      and for boys 7-8, 11-12, 16-17, and 18-19 years old, also for increases between
      these age classes in towns and villages separately. This is an extension of the
      analysis based on the correlation of these traits in 9.5-year-old girls and 11.5
      year-old boys (Wolanski et al. 1990). The regression of somatic-fitness traits on
      some demographic and economic properties of regions (regional factors) is most
      significant for rural boys, a little less significant for rural girls, and it is
      weakest for urban boys. The largest differences in the regression of somatic
      fitness traits on regional factors between age classes were noted for rural
      girls, moderate for urban youth, and the smallest for rural boys. Dependence of
      somatic-fitness traits on regional factors increased with age. It was most
      clearly expressed in urban boys, and least clear in rural girls. But the
      strongest relationships at an age of 18 years occurred only in towns (for both
      sexes), whereas at an age of 9 years for rural girls and at an age of 16 years
      for rural boys. The analyzed traits of body build and physical fitness in youth
      were most strongly related to the percentage of urban population in a region,
      especially for urban and rural boys and rural girls. In urban girls, the most
      important factor was migration rate. Generally, the second most important factor
      influencing somatic-motor traits was electric energy use per 100 km2. The
      strongest effect of regional factors on motor-fitness traits was recorded for
      runs, standing long jump, and sit-ups, whereas running broad jump (normalized on
      stature) and trunk flexibility were least affected. Among body build traits, Kaup
      index and chest circumference were most affected, whereas arm circumference
      (normalized on stature twice stronger), and chest flexibility were least
      influenced. For example, the strongest relationship was noted between Kaup index
      (35.1%) in 9.5-year-old girls and regional infant death rate.

PMID- 1344724
TI  - Respiratory-cardiovascular adaptations in 7-49-year-old inhabitants of selected
      regions of Poland.
AB  - This paper is based on the examination of 2789 individuals of both sexes, aged 7
      8, 10-11, 14-15, and 29-49 years, inhabiting the Suwalki region (S), Lublin Coal
      Basin (LCB), Belchatow Industrial Center (BIC), Dabrowa Basin in Silesia region
      (DB) and the city of Lodz. Some respiratory-cardiovascular system and blood
      traits were analyzed (apnoea, minute lung volume, vital capacity, hemoglobin
      concentration, hematocrit index, systolic blood pressure, and heart rate). It has
      been found that compensation of function within the respiratory and the
      cardiovascular system (an increase in some traits combined with a decrease in
      some others) is a characteristic way of adaptation to an agricultural environment
      with a harsh climate (the Suwalki region). In areas under industrialization (LCB
      and BIC) a functional compensation was observed for all the features under study.
      In DB, phenomenon of compensation was observed in children, and symptoms at the
      border of non-adaptation and overadaptation (most traits had average values,
      whereas respiratory and blood traits tended to be above average) were noted in
      adults. The inhabitants of Lodz were characterized by a high minute volume and
      long apnoea. Children were characterized by a compensation within the respiratory
      and the cardiovascular system, whereas in adults the response ranged from
      compensation within traits of one of the functional systems to the phenomenon at
      the border of non-adaptation and overadaptation.

PMID- 1344725
TI  - Sexual dimorphism in newborns and adults.
AB  - A total of 1034 newborns were used to analyze sexual dimorphism with respect to
      37 somatic traits and ratios between them, describing body shape. Arithmetic
      means and standard deviations were calculated for both sexes. Similarly, sexual
      dimorphism of adults was analyzed. Sexual differences in newborns were
      statistically significant for most measurements but only for some body
      proportions (relative chest size, foot shape, relative lower extremity length,
      and the ratio of head to chest circumference). The highest degree of sexual
      dimorphism in newborns was shown by the index standardized on the mean
      (dsex/mean) of such traits as the thickness of subcutaneous fat tissue on the
      thigh, subscapular fat tissue and fat tissue on the 10th rib, body weight, hand
      breadth, and relative chest size (Marty index). A moderate dimorphism was found
      for the length of upper extremities, forearm with the hand, head with the neck,
      hand and trunk, the size of the nose and foot, the breadth of hips and mandible,
      and the upper-face height. A low dimorphism was found for body length,
      circumference and breadth of head, face diameter, chest circumference, foot
      shape, relative length of lower extremities, and proportion between head and
      chest circumferences. Sexual differences (dsex/mean) for all the somatic traits
      examined in adults were statistically significant. The dimorphism of all the
      traits (except hip breadth) was higher in adults than in newborns. The highest
      increase in sexual dimorphism was noted for chest breadth (ca 55 times), then for
      chest depth (ca 17 times), thickness of subcutaneous fat tissue on arm (ca. 17
      times), and the length of lower extremities (ca 15 times). Sexual differences in
      proportions (shape) of the body were also better pronounced in adults than in
      newborns. Sexual dimorphism standardized for dispersion (dsex/SD) in newborns
      differed from that in adults with respect to the degree of its expression and the
      sequence of the traits showing the highest and the lowest levels of dimorphism.
      This results from intra-group variation of different traits.

PMID- 1344726
TI  - Proportion of some somatic, physiological, and psychomotor traits to extreme
      values of selected morpho-physiological traits in humans.
AB  - The material analyzed in this paper consists of inhabitants of the Suwallki
      region (rural area), Belchatow Industrial Center (under industrial development),
      Dabrowa Gornicza Region (heavy industrial region) and Lodz (textile industry
      city). A total of 1012 individuals of both sexes were examined. They were aged
      from 4.5 to 24.4 years, and characterized by extreme values (small or large) of
      five basic traits (body weight, vital capacity of lungs, heart rate after work,
      hematocrit index, and diastolic blood pressure). Individual morphological,
      physiological, and psychomotor traits were examined in relation to extreme values
      of these five basic traits. It has been found that some traits were compensatory
      with respect to the basic traits, but some others were adapted in different ways.

PMID- 1344727
TI  - The effect of culture and genotype on motor development of parents and their
      children.
AB  - The study is based on the observation of 3995 individuals aged from 3 to over 80
      years from five habitat types of Poland, ranging from agricultural villages to a
      large industrial city. We used a set of motor tests described elsewhere and
      examining the static and explosive muscular strength, agility, coordination and
      persistent fitness. The study objects were the generations of parents and their
      children (because of age-dependent differences, the traits of the latter were
      expressed in T-scores). Factor analysis with rotation Varimax was used to examine
      family traits. Four latent factors characterizing families were identified.
      Factor 1 (F1) was related with culture (consciousness). It explained 26% of the
      variance. F2 described living conditions and explained 22% of the variance. F3
      (maternal-genetic) explained 12% of the variance, and factor 4 (father's genetic
      factor) explained 11% of the variance. These factors have a stronger effect on
      the motor traits of parents than on those of their children. The two generations
      were more similar with respect to such traits as the static strength,
      flexibility, spatial orientation and persistence. They were little similar with
      respect to explosive power and running agility. A moderate similarity occurred
      for throw accuracy and body balance. The most important factor in the parental
      generation is the consciousness (culture level) co-occurring with fitness (only
      for throw accuracy these were living conditions). The most important factors in
      the descendant generation were usually beyond the examined family traits. The
      present results show that in parallel to genetic and maternal factors also
      cultural factors related to traditional customs and social practices determine
      motor traits of children.

PMID- 1344728
TI  - Age-dependent changes of some somatic traits and endurance fitness of men 18-55
      years of age.
AB  - The purpose of the study was to determine the range of involution changes
      concerning some somatic traits and endurance fitness in men 18-55 years of age.
      The material consisted of 155 workers from different plants, all living in towns,
      who were examined twice at a 7-year interval. Six somatic traits were measured
      and analysed: body height, body weight, chest circumference, skin-fat fold
      thickness (scapula, shoulder, hip). Maximal oxygen uptake was measured indirectly
      by recording the pulse rate during submaximal effort. The results were evaluated
      statistically by calculating the mean, the standard deviation and the
      significance of arithmetical mean differences. First step regression equations
      were applied to evaluate involution changes in body height and VO2 max. It was
      found that: Individual changes in body height began approximately in the 39th
      year of age. Decline in body height in men increased with age. At about the 32nd
      year of life the maximal oxygen uptake significantly decreased in the examined
      men but the process does not tend to intensity with age. After 7 years VO2 max
      (1/m9n) index decreased 12% in the 31-40 year-olds and 9% in the 41-55 year-olds.

PMID- 1344729
TI  - Atherosclerosis risk factors in the inhabitants of the nascent Coal Basin of
      Lublin region.
AB  - There were examined 222 men and 253 women over 18 years of age, selected at
      random from among country people living in the area of the nascent Coal Basin of
      Lublin district. There was determined their height and body weight, degree of
      overweight, general fat content in the body, arterial systolic and diastolic
      blood pressure as well as blood serum cholesterol concentration, concentration of
      triglicerides, glucose and uric acid in the blood. It was found out that the
      level of studied vascular atherosclerosis risk factors in the population under
      study was lower than the level found by the Polish Experiment in other
      populations.

PMID- 1344730
TI  - Biological traits of spouses: socio-cultural and economic context in the urban
      and rural environments.
AB  - The study covered 89 typical rural families and 161 typical urban families in a
      few of Polish regions, determining 39 features (morphological, physiological and
      psychomotor, morbidity, level of education, income and living conditions as well
      as fertility) of spouses and family. The families compared thus from the years of
      the best economic conditions (1975-1976) of post-war Poland are different from
      those described today for other periods and populations. Differences in the
      majority of somatic features, which are positive indices of health, are
      insignificant. Some of them, are better developed in urban populations (stronger
      physique, better nutritional status, lower blood pressure, better respiratory
      indices), others--in rural populations (greater muscle strength in women, shorter
      time of reaction). Urban population has been seen to have a higher morbidity than
      the people of rural areas. Differences in such a constant features as the shape
      of head point at the process of directional migration from villages of
      brachycephalic people. This shape of head is probably linked with improper
      nutrition (deficit of mineral components etc.).

PMID- 1344731
TI  - Urbanization and industrialization versus biological status of human populations.
AB  - The paper concerns the biological status of the Polish population. A comparison
      was made for inhabitants of towns, villages, and areas under different levels of
      industrialization and environmental pollution. It has been found that urban
      populations as compared with rural ones were characterized by a smaller number of
      children within a family, higher natural abortion rate, and higher infant
      mortality (estimated during the first 24 hours of life). An analysis of birth
      rate in three groups of birth weight has shown that rural habitats were more
      suitable for prenatal development than urban habitats, as a higher proportion of
      newborns had optimum body weight at birth in villages. It has been observed that
      the biological status of fetus (estimated as the body weight at birth) depended
      on the socio-economic conditions (a relatively high birth rate with optimum body
      weight in the first half of the 1970s, and a low birth rate in the years of the
      social crisis in Poland in 1981-82). Moreover, it has been found that in
      agricultural areas relatively little polluted (the Suwalki region), birth rate
      and total mortality were high, respiratory traits reached highest values, and
      blood pressure was low as compared with values of these traits in other areas of
      Poland. The inhabitants of industrial centers (Puchaczow, Bukowno) were exposed
      to heavier environmental pollution than the rural population, and at Puchaczow
      they were characterized by a short stature and low body weight. The seaside
      region (Jastarnia) was over-crowded and also affected by the pollution of the
      Puck Bay. Both these factors could account for a high mortality and emigration
      rate. Inhabitants of the areas being industrialized (Belchatow) were
      characterized by a low total mortality, below average for infants, poor
      development of the respiratory system, but a high psychomotor fitness. In the
      city of Lodz and in Strzemieszyce, environmental pollution was very high, which
      was combined with a very high total mortality, and in Lodz also with a high
      infant mortality. In Strzemieszyce, the values of some physiological traits such
      as Hb and HR were increased.

PMID- 1344732
TI  - Family and couple properties, and placenta weight in the populations of Bialystok
      and Zambrow, Poland.
AB  - The purpose of this study was an analysis of relationships between the traits of
      families and parents, also recognition of factors determining family properties,
      including factors responsible for placenta weight. Correlation matrix was used to
      find relationships among traits, and factor analysis with rotation of the Varimax
      type was used to identify factors. A total of 795 women were examined, including
      their placenta and family traits, in the regions of Bialystok and Zambrow, in
      1977-1978. A correlation matrix of 23 traits of the family and couple, and the
      weight of placenta during a given pregnancy, was analyzed. A total of 8 factors
      were discerned, explaining 61.3% of the total variation of the traits. Factor 1
      (F1) represented the culture (consciousness) of the family and morbidity of the
      mother (15.2%), F2-parental age at pregnancy of a given mother (10.4%), F3-living
      conditions (8.1%), F4-arterial blood pressure of mother (8.1%), F5-body size of
      the mother (6.5%), F6-traits of the menstrual cycle and morbidity of the mother
      (5.6%), F7-body size of the father (4.7%), and F8-characterized father's
      morbidity (4.4%). A relatively low but statistically significant correlation was
      found between the weight of placenta, on the one hand, and the weight and stature
      of the mother and number of pregnancies, on the other hand. A little higher
      correlation was found between the weight of placenta and the morbidity of the
      mother.

PMID- 1344733
TI  - Studies of Bialystok and Zambrow (Poland) newborns, their families, and duration
      of pregnancies from which they were born.
AB  - The paper presents a preliminary analysis of the properties of the 1034 families
      of newborns examined in 1977-78 in Bialystok and Zambrow. This analysis also
      involves the course of pregnancy and delivery, placenta properties, and some
      traits indicative of the new born status (including diseases, malformations,
      trauma, blood groups, serological conflict, adaptability, mortality). According
      to the results the mean age at mother's maturation was 14.4 years, the most
      frequent season of the menarche was summer (38.2%). The mean age of mothers at
      delivery was 26.3 years, and that of fathers 29.3 years. The mean stature was
      161.4 cm for mothers and 173.6 cm for fathers. The average increase in mother's
      body weight over the 20-week pregnancy period was 6.4 kg. Mean birth weight was
      3.48 kg in boys and 3.36 kg in girls, mean placenta weight was 493.6 g of male,
      and 484.7 g of female fetuses. The majority of newborns was healthy. Only about
      1.3% of the newborns suffered from typical diseases of newborns, 1% had inborn
      malformations, and 1.4% were injured.

PMID- 1344734
TI  - Latent factors in body build of newborns.
AB  - The paper is focused on relationships between traits of newborns and on
      discerning factors characterizing newborns more generally than individual traits.
      For this purpose a factor analysis was made using 35 somatic traits of 1013
      newborns examined in hospitals of Zambrow and Bialystok. Main components were
      found from the correlation matrix, and after the orthogonal rotation of the
      Varimax type, eight independent factors were identified. The body weight was
      highly correlated with circumferences of chest, calf, forearm, head, and arm.
      Body length was correlated with the length of lower extremities, the length of
      upper extremities was correlated with the length of arm and with the breadth and
      depth of chest, circumferences of different body parts were correlated with each
      other, and this was also the case of the thickness of three skin-fat-folds. The
      following factors were found as a result of the factor analysis (in parentheses
      there are traits showing highest correlations with a given factor, thus, most
      suitable for monitoring studies): F1-body weight (thigh circumference), F2-upper
      extremity length, F3-subcutaneous fat tissue (skin-fat-fold thickness on rib 10),
      F4-face length and nose diameters (upper-face height), F5-scapular-arm-hip
      diameters (scapular breadth), F6-trunk length (trunk length), F7-body length
      (length of lower extremities), and F8-head breadth diameters (mandible breadth).

PMID- 1344735
TI  - Secular changes in human fetuses normally aborted in years 1965-1985.
AB  - The authors disposed of numerous cases of fetuses normally aborted during the
      long period of time therefore the studies of time dependent variability of some
      somatotropic features in relation to the degree of development were decided. The
      studies on the fetal material should be always performed with great care as many
      errors could be introduced. Some of them are related to not enough accurate
      determination of the fetal age and the variability of the causes of abortion.
      These would result the inconsistency of stages of fetal development among the
      material used for the study. Therefore the research was performed using only the
      fetuses with accurate estimated calendar age and of similar environmental
      conditions for development. The causes of the abortion were related only to
      external factors but not to the course of pregnancy. For the analysis only the
      fetuses of 5th and 6th month of fetal age were used. All fetuses were aborted in
      the years 1965, 1970, 1975, 1980, 1985. The intersexual differences were also
      taken into consideration and calculated means of the features were related to
      identical points of the fetal age. The variations in the seating body length (v
      tub), the head perimeter, the shoulder width (a-a) and the body weight were
      analysed in such individualised groups.

PMID- 1344736
TI  - Values of somatic traits and of body proportion indices in male and female
      newborns of Lublin.
AB  - Between December 1984 and May 1985, anthropometric measurements were applied to
      455 full-term and healthy newborns (225 boys and 230 girls). The purpose of the
      investigation was to learn about somatic development and body proportions of
      Lublin newborns. It has been found that although the studied somatic traits show
      bigger differences between newborns of the same sex, rather than between newborns
      of the opposite sexes, sexual dimorphism of morphological traits apparently
      starts already at birth. Out of the analysed somatic traits and calculated body
      proportion indices, the following ones have significantly bigger values on boys:
      body mass and length, length of trunk with head and neck, length of trunk alone,
      hip width, shoulder width, width of distal femoral epiphysis, head length, width
      and circumference, and Quetelet index. In girls, in turn, thickness of three skin
      folds and shoulder-hip index are statistically more prominent. Mean values of
      somatic traits and body proportion indices may serve the purposes of regional
      standards for the evaluation of newborns in Lublin itself as well as in other
      towns of similar characteristics.

PMID- 1344737
TI  - Evaluation of acceleration of somatic development of Lublin newborns over the
      period of twenty years.
AB  - The material for the present investigation includes the results of Chrzastek
      Spruch's 1964-65 analysis of acceleration in 290 newborns (150 boys and 140
      girls) as well as the data coming from the measurements applied to 445 newborns
      (225 boys and 230 girls) in 1984-85. The comparison between mean values of
      somatic traits of these two investigations points out to the presence of
      acceleration of physical development of Lublin newborns. The process involves
      increases in body length, lower extremity length, upper extremity length, and hip
      width. The width of distal femoral epiphysis is found diminished, which may
      attest to the process of gracilisation. Sexual dimorphism index turns out to be
      decreased, which is related to the fact that male and female body proportions
      tend to be alike. Moreover, newborns' body structures tend to become slender,
      which is signalled by lengthening of lower extremity and diminishing differences
      between shoulder width and hip width.

PMID- 1344738
TI  - Screening of white middle-class US infants with the Wolanski Gross Motor
      Evaluation.
AB  - The purpose of this study was to evaluate the appropriateness of the Wolanski
      Gross Motor Evaluation (WGME) to screen Triangle Area (North Carolina, US)
      infants for developmental delay. Eighty full-term, white infants were tested once
      each and five infants were followed longitudinally using the WGME. The results of
      the study revealed that the Triangle Area infants scored significantly higher
      than did the Polish infants with whom the study was normed at three and six
      months of age, but not at nine and twelve months of age. At three and twelve
      months scores differed between males and females, with females scoring higher
      than males. No significant differences according to gender occurred at six or
      nine months. Longitudinal subjects did not remain in any single channel of
      development on either the existing WGME grids or on grids fabricated from the
      cross-sectional data from this study. The WGME grids would not be appropriate for
      use with American infants as they now stand. Further research is needed to
      develop appropriate scoring methods, as well as provide validity and reliability
      information.

PMID- 1344739
TI  - Biocompatibility and IOL.
AB  - "Biocompatibility": meaning, investigation and importance for intra-ocular
      lenses. As PMMA isn't as biocompatible as initially thought, one searches for
      other materials on the one hand and tries to modify the surface of the PMMA on
      the other. For the latter only the HSM (heparin surface modifying) technique is
      currently used.

PMID- 1344740
TI  - Stellar corneal rupture and secondary glaucoma after squash trauma in a
      keratotomized eye.
AB  - We report an unusual dramatic case of stellar ocular rupture after squash blunt
      in a recently keratotomized eye through weakened keratotomy scars. The early
      secondary glaucoma, the tension generated by the surgical sutures of the wounds
      and the use of systemic and topical steroids could explain the reopening of two
      incisions initially unperforated and the delayed healing procedure. We also
      stress the benefits of wearing protective eye glasses when playing squash, as
      well as a strict legislation in Belgium in such an eye-threatening sport.

PMID- 1344741
TI  - [Neurosurgical approach to orbital tumors].
AB  - The transcranial approach to the orbital tumors consists of a subfrontal route
      after frontal or frontotemporal craniotomy to allow epidural access to the
      orbital roof. This approach is used for all tumors with intracranial extension as
      well as for tumors located in the apex of the orbit or medial to the optic nerve
      in the posterior part of the orbit.

PMID- 1344742
TI  - Chemical and thermal lesions in the orbital region.
AB  - In severe chemical and thermal burns the surroundings of the globe are frequently
      affected. Longstanding inflammatory reactions and severe scar formation around
      the globe are consequences from such damage. Lids, tarsi, conjunctival and
      subconjunctival tissues down to the fornices and the anterior orbit are
      destroyed. Beside medical therapy various operations are necessary to restore an
      environment for the globe to allow its survival.

PMID- 1344743
TI  - Hyperthyroidism, ophthalmoplegia and unilateral mydriasis.
AB  - Clinical description of a 33 years-old woman, with hyperthyroidism, admitted to
      the emergency unit with external bilateral ophthalmoplegia and left mydriasis,
      unreactive to light. The external ophthalmoplegia is proven to be due to
      myasthenia. The left mydriatic pupil demonstrates features typical for Adie's
      tonic pupil. The association of a tonic pupil with an auto-immune disease is
      infrequent. The axiom that internal ophthalmoplegia in a patient with external
      ophthalmoplegia excludes myasthenia gravis should be reevaluated.

PMID- 1344744
TI  - Dysthyroid orbitopathy: invasive treatment and the value of radiotherapy.
AB  - In this retrospective review of 29 patients with severe dysthyroid orbitopathy,
      the authors compare 3 invasive therapeutic modalities corticosteroids,
      radiotherapy and surgical orbital decompression) with special emphasis on the
      role of radiotherapy.

PMID- 1344745
TI  - Non-invasive diagnosis of the localisation of the fistula in dural carotid shunt:
      a case presentation.
AB  - An illustrative case is reported to demonstrate the possibilities of MR
      angiography in carotid -cavernous fistula (CCF). This new non-invasive technique
      may be useful in the diagnosis and follow-up. If an embolisation is anticipated
      conventional angiography is still necessary because of the higher spatial and
      temporal resolution.

PMID- 1344746
TI  - Experimental approach to surgical treatment of lacrimal insufficiency by
      microvascular submandibular salivary gland autotransplantation.
AB  - When compared to the parotid duct transposition, the microvascular submandibular
      salivary gland autotransplantation presents the advantage of providing a more
      viscous tear substitute, and a basal flow rate unaffected by meals. If future
      attempts to re-innervate the graft are successful, this procedure could be
      promising in restoring an acceptable lacrimal function in severe xerophthalmia.

PMID- 1344748
TI  - Treatment of posterior eye segment complications after perforating trauma.
AB  - 168 perforating trauma cases that underwent vitreoretinal surgery in our hospital
      over a two year period were reviewed. A uniform surgical concept was applied in
      those severely injured eyes. Showing posterior eye segment complications that
      required vitreoretinal surgery and having at least light perception were the only
      two criteria to be eligible for this study. The anatomic and functional results
      in different trauma groups are discussed as well as indications and duration of
      silicone oil tamponade.

PMID- 1344747
TI  - Surgery on the extra-ocular muscles after orbital fracture.
AB  - We analyzed the files of 61 patients presenting with diplopia due to orbital
      fractures. Thirty-four patients needed a primary orbital reconstruction and this
      diminished the complaints of diplopia in most cases. In only 5 cases additional
      ocular surgery on the extra-ocular muscles was indicated. Of the 27 patients who
      did not require orbital surgery, 5 underwent extra-ocular muscle surgery to
      diminish diplopia. We present our guidelines for treatment, based on forced
      duction testing, ocular motility, primary position and field of binocular single
      vision.

PMID- 1344749
TI  - Retinal periphlebitis and retinal pigment epithelium changes associated with
      multiple sclerosis: a report of two cases.
AB  - Two patients with definite MS and no significant visual loss are presented,
      because of the marked bilateral sheathing of retinal veins, and diffuse
      pigmentary changes in the first patient, and the previously unreported paravenous
      pigmentation with bone corpuscular configuration in the second patient. The
      lesions in the second patient are similar to paravenous retinitis pigmentosa. We
      assume that the RPE lesions may be secondary to perivasculitis, which is not
      uncommonly seen in MS patients.

PMID- 1344750
TI  - Short term results with excimer laser-photo-refractive keratectomy.
AB  - The results at three months after photo-refractive keratectomy surgery (PRK) with
      the Meditec Mel 60 laser are discussed. A total of 86 eyes (18 hyperopes and 68
      myopes) were followed. The predictability of +/- 1D in the myopia group of less
      than 6D was 86% and it was 68% in the myopia group of more than 6D. The
      predictability of +/- 2D was 96% in the group below 6D, and in the group of more
      than 6D it was 85%. In hyperopia, the mean refractive change was 2.7D and 44% of
      eyes were between +/- 1D at three months after Excimer laser surgery.

PMID- 1344751
TI  - A long term clinical trial of carteolol in the management of glaucoma. Belgian
      Carteolol Study Participants.
AB  - Carteolol is a nonselective beta-blocker with intrinsic sympathomimetic activity
      (I.S.A.). A multicenter trial was started to check if the theoretical advantages
      of this new drug could also be confirmed in a clinical setting. The intraocular
      pressure (I.O.P.), the visual field and the adverse reactions were evaluated at
      day 8, 60, 360 and 960. The results of this study demonstrate that carteolol
      effectively lowers the I.O.P. with minimal adverse side effects in previously
      treated as well as untreated patients.

PMID- 1344753
TI  - Structural, hemispheric theory of eye, movements and its confirmation by dynamic
      orbital magnetic resonance imaging.
AB  - Two models of eye-movements are in competition with each other: the cardanic
      suspension (Listing law 1845) and the socket-joint (structural-hemispheric theory
      1986). The dynamic orbital MRI demonstrates arguments for the latter which is
      based upon anatomy and physiology.

PMID- 1344752
TI  - Blindness following paranasal sinus surgery: a report of two cases.
AB  - Two cases of blindness following paranasal sinus surgery are presented. The first
      patient, a 38-year old man, developed a delayed massive haemorrhage, after
      bilateral sphenoethmoidectomy. This hemorrhage could be stopped by electric
      cauterisation under endoscopical control. During this reintervention the patient
      developed total blindness of his right eye, and a restriction of the
      inferotemporal left visual field. The second patient, a 10-year old girl,
      developed, after bilateral spheno-ethmoidectomy for isolated sphenoiditis, total
      blindness of the left eye and paralysis of the ipsilateral extraocular muscles.
      According to the literature, blindness secondary to paranasal surgery is mainly
      due to retrobulbar hemorrhage. In the first case blindness was due to a direct
      cauterisation of the optic nerve, after perforation of the lamina papyracea. In
      the second case, blindness was probably due to a hemorrhage in the orbital apex.

PMID- 1344754
TI  - Pathogenesis and treatment of the ophthalmopathy associated with Graves' disease.
AB  - The pathogenesis and etiology of the ophthalmopathy associated with Graves'
      disease still remains to be elucidated. There is, however, general consensus that
      the extraocular muscles are the principal site of the autoimmune response and
      that the main changes are in the interstitium. The primary target seems to be the
      fibroblasts which are stimulated as a result of cytokine release by the activated
      T-cells that accumulate in the muscles. Increased production of
      glycosaminoglycans and collagen by fibroblasts, attracts water to the
      interstitium and produces interstitial oedema. The frequent association of
      Graves' thyroid disease and ophthalmopathy favours the hypothesis of antibodies
      cross-reacting with antigens of orbit and thyroid. Although cross-reactivity is
      very attractive, the nature of the involved antigen remains unknown. Since
      Graves' ophthalmopathy is an autoimmune disorder, many immunomodulatory agents
      have been used in the treatment of this disorder. Anti-inflammatory and
      immunosuppressive treatment modalities will be reviewed.

PMID- 1344755
TI  - Congenital Marfan syndrome with contractures. A clinicopathological report.
AB  - Children with CMC present with blue sclerae, megalocornea, hypoplastic and
      translucent irides, miosis and high myopia. The lenses may be dislocated as in
      familial Marfan syndrome but they are often in place and microspherophakic. The
      clinical history of a boy with CMC is presented. Pathological examination of the
      eyes showed megalophthalmos with thinned sclera, anomalies of the chamber angle
      and iris, ill-developed ciliary body and choroid and a small in situ lens.

PMID- 1344756
TI  - The use of the first locally manufactured epikeratolens for keratoconus in
      Leuven.
AB  - We adapted a lathe to the production of keratolenses. A cornea is mounted on a
      chuck and frozen at minus 40 degrees C. Hereafter we can cut the desired
      posterior radius and diameter. The first plano keratolens produced was used to
      correct keratoconus. The favourable result encouraged us to manufacture
      keratolenses for the correction of refractive errors.

PMID- 1344757
TI  - Epilepsy: 'providers' and 'purchasers' on one site.

PMID- 1344758
TI  - Who needs neurological imaging?

PMID- 1344759
TI  - Memory complaints, memory disorders and focus localization in patients with
      partial epilepsy.
AB  - Our study aimed at analysing effects of epileptic foci on memory function in
      patients with partial epilepsy. Twenty-eight patients with spontaneous memory
      complaints and psychometrically established memory disorders were assessed by 21
      channel electroencephalography recorded both during cognitive testing and during
      99mTc-HMPAO single photon emission computed tomography (SPECT). Computed
      tomography (CT) was performed on the same day. None of the epilepsy-related
      factors (seizure type, seizure frequency, type of epilepsy, age at onset of the
      seizures, type of antiepileptic treatment) could be related directly to severity
      or type of memory impairment (classified into the categories 'global', 'verbal'
      and 'non-verbal'). Remarkably, this study found no significant relationship
      between EEG focus localization and severity of measured memory impairment. Most
      areas with hypoperfusion on the SPECT were found in the group with global
      (severe) amnesia, typically with a right frontal localization. Abnormalities on
      CT were predominantly found in the same group, however, with a right-sided
      parietal localization. An unanticipated finding was that the majority of temporal
      CT and SPECT lesions were found in the group with relatively better memory
      performance.

PMID- 1344760
TI  - Vigabatrin in adults with poorly-controlled epilepsy and learning disabilities.
AB  - Twenty-two adult patients with uncontrolled epilepsy and severe learning
      difficulties were included in an open study of vigabatrin. Patients were all in
      residential care and had experienced at least 12 seizures during the previous 12
      months despite all attempts to optimize antiepileptic drug (AED) treatment.
      Following a 4 month baseline period, vigabatrin 500 mg twice daily was added to
      the current AED treatment and the dose increased according to response, up to a
      maximum of 4 g/day. Ten patients achieved a reduction in seizure frequency of
      more than 50% during this 4 month dose titration phase. Two patients had no
      seizures during the baseline period. For the 30 patients with seizures during the
      baseline period the median improvement in seizure frequency with the addition of
      vigabatrin was 49% (P = 0.014). The response rate was higher for patients with
      partial seizures than for those with generalized seizures. Ten patients continued
      with vigabatrin while the dose of one of their other AEDs was gradually reduced
      and successfully withdrawn in three patients. Adverse events were reported in 20
      patients during the 64 week study period. The most frequently reported events
      were sedation (8 patients), aggression (4 patients), agitation (3 patients) and
      ataxia (3 patients). No patients were withdrawn from the study as a consequence
      of adverse events. Vigabatrin was therefore an effective add-on therapy in 45% of
      these difficult-to-treat patients and allowed reduction of other AED treatment in
      a small number.

PMID- 1344761
TI  - MRI findings in epileptic patients on vigabatrin for more than 5 years.
AB  - Although vigabatrin is a promising new antiepileptic drug, its safety has been
      challenged by the report of dose-dependent central nervous system myelin
      vacuolation in some preclinical animal studies. Since it has been shown that
      vacuolation is associated with specific magnetic resonance imaging (MRI) findings
      in rats and dogs, MRI of the brain was performed in 11 patients with complex
      partial seizures who had been receiving vigabatrin for 64-78 months (mean 74.0 +/
      5.0 sd) as additional treatment for epilepsy, with a cumulative exposure ranging
      4200 to 9360 g. In no case did MRI show white matter changes similar to the
      pathological findings of microvacuolation observed in animals. These results
      would appear to confirm that current doses of vigabatrin do not cause myelin
      vacuolation in humans, even for treatment periods of longer than 5 years.

PMID- 1344762
TI  - Vigabatrin in the treatment of complex partial seizures.
AB  - We report the effect of vigabatrin on seizure frequency in 13 severely drug
      resistant patients with intractable complex partial seizures (CPS) with or
      without secondary generalization. Patients were followed for a 3-month period
      before vigabatrin administration to establish a 'baseline'. Six patients became
      seizure free for 2-3 weeks immediately after starting vigabatrin. In seven
      patients a transient (4-6 weeks) increase in seizures above baseline occurred,
      which was attenuated by vigabatrin dose increments. After 3 months, the mean
      baseline CPS frequency was reduced from 7.75 +/- 1.18 (median 8, range 2.6-16) to
      2.77 +/- 0.7 (median 1, range 0-7). At 6 months a > 50% improvement remained in
      seven patients. After 12 or more months CPS frequency returned to baseline in
      four patients, improved (by 25-62.5%) in four and deteriorated in three. One
      patient who was seizure free lost control at 16 months. Other effects were
      drowsiness (3), weight increase (3), diarrhoea (1), depression (2) and mood
      elevation (2). Four patients discontinued vigabatrin; one because of severe
      depression, three owing to lack of efficacy. Three patients have undergone and
      two are awaiting neurosurgery for their epilepsy. Thus, CPS frequency
      progressively deteriorated toward baseline in all patients, however, secondary
      generalizations were abolished in four and reduced in two.

PMID- 1344763
TI  - University students with epilepsy: a study of social aspects.
AB  - Improved control of epilepsy has permitted an increasing number of young persons
      with epilepsy to attend university. This study was designed to assess the impact
      of epilepsy on their education, employment, family and social life. We studied
      fifteen randomly selected full time university students, aged 20-28 years, who
      had a well documented history of partial or generalized epilepsy. One third still
      had seizures, over 90% were taking antiepileptic medication and all were followed
      by a neurologist. Interviews were conducted according to a standard open-ended
      questionnaire lasting 1.5 hours. After an initial adjustment period, most did not
      feel that epilepsy constituted a handicap to their education. They learned about
      epilepsy, did independent research and one quarter chose careers in the health
      sciences. Most reported occasional negative experiences, but were reluctant to
      interpret this as evidence of discrimination. All felt that they had had equal
      opportunities at school and at work. They were selective about imparting
      knowledge about their seizures to students, staff and employers, but did not hide
      their epilepsy. Subjects had high vocational aspirations and academic motivation
      reflecting good intelligence and previous educational achievements. Their
      positive attitude, enthusiasm and denial of difficulties were striking. This
      reflects improved seizure control as well as family and social support in this
      group of young people.

PMID- 1344764
TI  - Central and peripheral benzodiazepine receptors in rat brain and platelets:
      effects of treatment with diazepam and clobazam.
AB  - Tolerance to the effects of benzodiazepines (BZ) may be mediated by changes in
      benzodiazepine receptors (BZRs). Peripheral BZRs (in brain and platelets) and
      central BZRs (in brain) were measured in rats following intraperitoneal
      administration of diazepam and clobazam each for 4 and 12 days. BZRs were
      measured by binding assays using [3H] PK 11195 (peripheral) and [3H]
      flunitrazepam (central) as radioligands. Diazepam, but not clobazam, increased
      peripheral BZR numbers in platelets (both P < 0.005), but not in brain, after 4
      and 12 days' treatment compared with appropriate controls. Neither drug altered
      central BZR affinities or numbers in rat brain. BZ effects on peripheral BZRs in
      platelets cannot be extrapolated to predict changes in brain receptors, either
      peripheral or central.

PMID- 1344765
TI  - Does chloroquine cause seizures? Presentation of three new cases and a review of
      the literature.
AB  - Three cases are reported of patients developing seizures whilst taking
      chloroquine. Recently, eight such cases have been reported elsewhere. A review of
      all patients described in the literature is given. Possible relationships between
      chloroquine and the occurrence of seizures are discussed and further studies
      recommended. At present we feel there is no need to restrict prescription of
      chloroquine to patients with a history of epilepsy.

PMID- 1344766
TI  - Liver function tests in persons receiving anticonvulsant medications.
AB  - Liver function tests were carried out in 206 adults and children taking
      anticonvulsants to ascertain the prevalence of biochemical abnormalities in
      asymptomatic patients. It was observed that serum gamma-glutamyl transpeptidase
      was elevated in 74.6% of patients, alkaline phosphatase in 29.7% and alanine
      aminotransferase in 25.2% of cases. These figures are similar to those previously
      reported in the literature and probably reflect hepatic enzyme induction by the
      anticonvulsants. It is suggested that there is no value in the routine
      performance of liver function tests in patients with epilepsy. However, such
      patients should be informed of the symptoms of hepatic dysfunction and asked to
      report for liver function tests should they have such symptoms.

PMID- 1344767
TI  - Epilepsy: patient perceptions of their condition.
AB  - The objective of this study was to ascertain the perceptions of people with
      epilepsy about their condition. Nine hundred and eight questionnaires were sent
      to members of epilepsy associations, with a 45% response rate, and 625
      questionnaires were sent to neurologists for their patients to complete, with a
      response rate of 16.5%. The results reinforce and extend previous observations
      that there is an ongoing need for educating health care professionals and persons
      with epilepsy about the condition. Matters pertaining to driving, the
      unpredictability of seizures, lack of employment and cognitive difficulties were
      of major concern to the respondents. The present data also highlighted the vexed
      relationship between stress and seizure control, which needs to be further
      investigated. These data should be of value to doctors and other health care
      professionals in their dealings with people with epilepsy. It should also provide
      epilepsy associations with data upon which they might be able to plan education
      services.

PMID- 1344768
TI  - Epileptic fits or infantile masturbation?
AB  - Two infants, one girl, 5 months old, and one boy, 6 months old, presented with
      rhythmic and sustained motor activities of a stereotyped nature accompanied by
      moaning and grunting, facial flushing and altered awareness. The episodes
      occurred frequently and were initially believed to be epileptic. Normal
      electroencephalograms during the fits, lack of response to antiepileptic
      medication given to one child and careful reviewing of videotape recordings,
      enabled us eventually to diagnose the 'seizure-like' episodes as masturbatory
      activity.

PMID- 1344769
TI  - Hot-water epilepsy in an adult: ictal EEG, MRI and SPECT features.
AB  - Reflex epilepsy constitutes a rare form of epileptic seizures. We observed a 20
      year-old man who presented with seizures induced by immersion in hot water. The
      trigger stimulus was specific. Contrast CT scan and MRI were all normal, not
      revealing any structural lesion. Ictal EEG recorded during a hot bath showed
      focal epileptic discharges in the left temporo-occipital area. Interictal SPECT
      showed a hypometabolism in the same cerebral region. Neuroimaging studies were
      rarely performed in this uncommon type of epilepsy. Nevertheless, in our case the
      result of the SPECT suggests a localized functional disturbance in the emergence
      of the disorder.

PMID- 1344770
TI  - The language of epilepsy.
AB  - The various names of epilepsy in European languages are reviewed. It is shown
      that they reflect the beliefs and misconceptions that were entertained in the
      past about the disease.

PMID- 1344771
TI  - Education in epilepsy consensus meeting. Overview of 10 September EEG round table
      meeting.

PMID- 1344772
TI  - Applications of molecular physics 'biotechnology' to the rational design of an
      improved phenytoin analogue.
AB  - This study exploits molecular physics, in conjunction with a large scale
      computing environment, as a tool for understanding the clinical phenomenology of
      phenytoin (PHT) toxicology at a molecular level and for employing this
      understanding in an attempt to design improved drugs. The application of
      molecular physics techniques, such as quantum mechanics and molecular force field
      calculations, to the process of rational anticonvulsant drug design remains
      virtually unexplored. A 3-step strategy for applying these techniques to the
      design of an improved PHT molecule is presented. Step 1 employs quantitative
      structure-activity relationship calculations on 80 PHT analogues to ascertain the
      portion of the PHT molecule necessary for bioactivity (i.e. the 'bioactive face'
      of PHT); the N3-C4(O)-C5-R fragment of PHT was identified as the bioactive face.
      Step 2 employs molecular modelling studies to determine the portion of the PHT
      molecule necessary for the teratogenic, mutagenic and connective tissue
      toxicities of PHT (i.e. the 'biotoxic face'); the C2(O)-N3 fragment of PHT was
      identified as the biotoxic face. Step 3 experiments design an 'improved' PHT
      analogue, which maintains the bioactive face while eliminating the integrity of
      the biotoxic face; 2-deoxy-5,5-diphenylhydantoin was designed and synthesized as
      the improved PHT analogue. This compound had biological activity equivalent to
      PHT, but was unable to bind to nucleic acids or to chelate metals involved in
      connective tissue metabolism.

PMID- 1344773
TI  - Memory effects following carbamazepine monotherapy in patients with complex
      partial epilepsy.
AB  - To evaluate the memory effects of carbamazepine (CBZ) monotherapy, a relatively
      large computerized neuropsychological test battery, specially developed to assess
      the properties of different memory systems, was administered to a group of
      patients with epilepsy in a pre-test--post-test control group design. Consistent
      with previous findings, the results show that CBZ treatment does not induce any
      general important or consistent negative signs of memory dysfunction. However,
      the epilepsy group as such demonstrates a relative inability to carry out more
      complex working memory tasks and they are also slower in simple long-term memory
      access tasks. Finally, the detailed findings suggest that CBZ plasma
      concentration levels within the therapeutic range are highly and negatively
      associated with short-term recency, which is a novel finding.

PMID- 1344774
TI  - Memory and attention in newly diagnosed epileptic seizure disorder.
AB  - Interictal disturbances of memory and attention were evaluated in 74 adults with
      newly-diagnosed untreated epileptic seizures and no other known brain pathology.
      In approximately 30% of the patients with cryptogenic seizures, the average
      memory and attention scores indicated subtle dysfunction compared with normal
      control group. The patients had difficulties in tasks requiring memory, sustained
      attention and flexible mental processing, whereas they had normal attention span,
      simple speed of tracking and simple psychomotor speed. The memory difficulties
      may be related to attentional dysfunction leading to impaired or slowed initial
      encoding of memory trace, and also to a deficit in storing process and
      hippocampal dysfunction. These findings could have important implications for
      establishing criteria for identifying patients who develop chronic epilepsy and
      who thereby would benefit from early therapeutic intervention.

PMID- 1344775
TI  - Sexual abuse and psychiatric symptoms in an epileptic population.
AB  - One hundred and seven consecutive patients attending the outpatient epilepsy
      clinic at a teaching general hospital were assessed by clinical interview for a
      history of sexual abuse. Questionnaires dealing with overall psychiatric
      symptomatology i.e., (SCL-90), (TSC-40) and depression (ZSRDS) were also used.
      The majority of subjects were single (60%), living at home (76.6%) and had an
      average age of 29 years. The mean duration of epilepsy was 18.8 years and the
      seizures were controlled with medication in 65.2% of patients. Ten (9.3%) of the
      subjects had been sexually abused. This frequency of sexual abuse is lower than
      in the general population and among psychiatric patients. The specific form of
      sexual abuse consisted of sexual intercourse (n = 4), fondling (n = 4) and oral
      sex (n = 2). The sexually abused subjects had significantly higher scores on the
      anxiety subscale of the SCL-90 and depression score on the ZSRDS than non-abused
      subjects.

PMID- 1344776
TI  - Epileptic seizures induced by sexual abuse. Pathogenic and pathoplastic factors.
AB  - Previous sexual abuse is now thought to be a common cause of non-epileptic
      seizures (pseudoseizures). However, since sexual abuse is common, a previous
      history of sexual abuse may also occur in people with actual epilepsy. We present
      six patients in all of whom sexual abuse may, by acting as a stressor in the
      already predisposed, have precipitated epilepsy and in some of whom the abuse may
      have affected the actual experiences of the epilepsy itself: all but one of the
      patients had partial seizures.

PMID- 1344777
TI  - Therapeutic drug monitoring improves seizure control and reduces anticonvulsant
      side-effects in patients with refractory epilepsy.
AB  - The benefit to patients of an on-site antiepileptic drug monitoring service, in
      which physicians' decisions were recorded before and after the concentration
      became available, have been assessed retrospectively. In 109 patients with
      refractory epilepsy monitored on three (n = 61) or four (n = 48) occasions
      between 1986 and 1990, one or more assay result was rated as 'unexpected' by the
      consulting doctor. In 51 of these, revision of the dose was undertaken as a
      consequence (active group). Their clinical outcomes were compared with those of
      the other 54 patients in whom the initial management plan was left unchanged
      (passive group). Median seizure frequency decreased in both groups, but this was
      statistically significant only for the actively treated patients [active group:
      first visit 1 (0 to 26) seizures/month, last visit 0 (0 to 19) seizures/month, P
      < 0.01, 95% CI -2 to -0.5; passive group: first visit 2.5 (0 to 57)
      seizures/month, last visit 1.5 (0 to 44) seizures/month, NS, 95% CI -1 to +10].
      The number of patients reporting one or more episodes of drug-related toxicity
      also favoured the actively managed patients (active group 25%, passive group 56%,
      P < 0.01). Within this selected group of patients, the anticonvulsant
      concentration was a better guide to clinical management than the physician's
      assessment.

PMID- 1344778
TI  - Absence epilepsy: early prognostic signs.
AB  - We have studied 124 children with typical absence epilepsy. The onset of symptoms
      was in 12% under 4 years, in 51% between 4-8 years and in 37% above 8 years. The
      F:M ratio was 2:1 in children under 4 years versus 1:1 above 8 years. Absences
      alone occurred in 82% and absences followed or preceded by generalized tonic
      clonic seizures (GTCS) in 6.5% and 11%, respectively. Simple absences were not
      seen in children under 4 years and were more frequent (14%) in the 4-8 years age
      group. Family history was positive for epilepsy in 20% and febrile convulsion in
      7%. Sixteen percent had a positive past history of febrile convulsions. All
      patients showed bilateral, synchronous spike-wave discharges from 2.5 to 4 c/s.
      Lateralized spikes, spike-slow wave complexes were found in 27%. Photosensitivity
      was present in 18% and was marked in 12%. Monotherapy with sodium valproate or
      ethosuximide (91% SV) was successful in 85% of patients with absences alone and
      68% of the absences with GTCS. Only 2% were not fully controlled either on
      monotherapy or polytherapy. Treatment was withdrawn in 41 patients and 13
      relapsed. We have identified four factors associated with relapses: (a) poor
      initial response to treatment, (b) lateralized focal EEG abnormality and/or
      marked photosensitivity, (c) the evolution to myoclonic epilepsy, and (d) early
      withdrawal of AED (< 3 years).

PMID- 1344779
TI  - Juvenile myoclonic epilepsy of Janz: clinical observations in 60 patients.
AB  - We studied 60 patients with juvenile myoclonic epilepsy (JME). There was a high
      positive family history for epilepsy (33.3%). Age at onset of epilepsy ranged
      from 4 to 18 years with an average of 13.9 years. 88.3% of patients were seizure
      free. The most effective drug was valproate. In eight patients drug withdrawal
      was attempted but all patients relapsed during a follow-up period of 1 year.
      Video-EEG studies were performed in eight newly diagnosed patients; myoclonic
      jerks were recorded in five patients.

PMID- 1344780
TI  - Diagnostic value of electroencephalography in arteriovenous malformations.
AB  - Arteriovenous malformations (AVM) are usually located superficially in the
      subcortical white matter, and seizures are one of the frequently seen presenting
      features of AVM. The diagnosis of AVM is confirmed with various neuroimaging
      techniques. The present study comprised six patients presenting with seizures and
      headaches, referred to the neurodiagnostic unit to rule out/confirm epilepsy. All
      patients showed epileptiform activity on electroencephalography (EEG). Further
      investigations, such as angiography supplemented with computed tomography (CT)
      showed AVM. EEG is usually not considered a valuable diagnostic tool in AVM, but
      our results support the finding that EEG is an extremely reliable investigative
      tool, and should be supplemented with angiography and CT scan for better
      localization of AVM.

PMID- 1344781
TI  - A matter of fried onions.
AB  - In the 1946 film 'A Matter of Life and Death', complex partial seizures were
      portrayed in detail and with surprising accuracy. This study was conducted to
      determine the nature of the medical collaboration in the preparation of the film
      as well as the reasons why the creative team of Michael Powell and Emeric
      Pressburger included these details, but elected to make them invisible to all but
      those with medical educations.

PMID- 1344782
TI  - [Place of microvascularized tissue transplants in emergency treatment of multiple
      trauma of the limbs. Excluding reimplantation].
AB  - When we evoked the indications of microsurgery in Traumatology, at first, we
      think reimplantations performed in emergency and also secondary management of
      soft tissues or complex defects. In fact, we resort to microsurgery in many other
      circumstances. Early microsurgical reconstruction of complex trauma of the
      extremities yield better results than delayed free flaps. In 7 cases, free flaps
      were performed on the lower extremities, in 2 cases on the upper extremities.
      Many advantages are credited with this offensive attitude which requires an
      appropriate organisation of the Departments of Traumatology, the intimate
      collaboration of surgeons called orthopedic or plastic surgeons, improperly
      divided by too administrative compartmentalization of the surgical specialties.

PMID- 1344783
TI  - [Prognosis in surgical treatment of cancer of extra-hepatic biliary ducts].
AB  - This work reports a retrospective multicenter study of the treatment and
      prognosis of 746 patients with gall bladder cancers and 684 patients with
      extrahepatic biliary duct cancers. Gallbladder cancers: Adenocarcinoma was
      encountered in 92.6% of cases, 107 were limited to the gallbladder. Removal was
      possible in 27% of the patients. Overall operative mortality was 21%. Overall
      survival at one year was 14%. The projected five-year survival for cancers
      limited to the gall bladder treated by simple cholecystectomy was 93% for
      noninvasive, "in situ" cancers. The survival was 18% with mucosal involvement,
      and 10% with extension to the gall bladder wall. Extrahepatic biliary duct
      cancers: Adenocarcinoma was encountered in 99.7% of assess; 40 were limited
      exclusively to the biliary ducts. 384 involved the upper 1/3 segment of the
      biliary duct, 86 the middle 1/3, and 121 for the lower 1/3. Cancers involving two
      or more of these segments were encountered in 93 cases. Removal of the cancer
      from these four locations was possible in respectively 30%, 50%, 50% and 7% of
      cases. Overall operative mortality was 27.7% and after removal: 13.5% for the
      upper biliary duct segment, 18.1% for the middle 1/3, and 20% for the lower 1/3.
      The mortality was 25% for cancer that involved two or more of these segments.
      Analysis related to age demonstrated a postoperative mortality of 16% in patients
      less than 70 years of age and 59.1% after 70 years. The five-year survival after
      surgery was projected to be 12% for cancers of the upper 1/3 segment, 15% in
      middle and 30% in the lower 1/3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1344784
TI  - [Desmoid tumors: diagnostic and therapeutic difficulties. Apropos of an unusual
      case].
AB  - This observation has been previously reported as a multifocal and recidivant
      desmoid tumor. The first time, the patient was operated on for a desmoid tumor
      situated on his left thigh. He was reoperated on fourteen years later for a
      recurrent tumor implanted on the same place and a new one on the right arm.
      Recently bilateral pulmonary tumors were discovered. As far as this evolution was
      concerned, its exceptional pattern induced a new analysis of the microscopic data
      and the diagnosis of fibrohistiocytic sarcoma was established. This observation
      suggest to the authors some comments about the difficulty of diagnosis and
      therapy of such soft tissue tumors.

PMID- 1344785
TI  - [Disabling rectocele: rectal plication by perineal approach. Apropos of 20
      cases].
AB  - Rectocele is a frequent rectal static disorder. Its usual clinical manifestation
      is a distressing outlet obstruction. Surgical treatments actually proposed are
      based on a trans-anal approach. Perineal approach has specific interests as shown
      on a consecutive series of 20 patients operated on between January 90 and January
      92. The surgical modalities were, after mobilization of the recto-vaginal wall,
      careful concentric folding of the rectocele followed by suturing the rectal
      fascia and pre-anal levatorplasty without associated colpectomy. Results (mean
      follow-up: 15 months) showed: 1) anatomic correction obtained in 18 cases,
      without local complications, but one dyspareunia, 2) restoration of normal rectal
      evacuation in 16 cases. The 4 functional failures were observed in patients with
      associated anorectal disorders (anismus, colon inertia).

PMID- 1344786
TI  - [Lumbar sympathectomy for arteritis. A reliable and (almost) seventy year-old
      technique].
AB  - The old procedure of lumbar sympathectomy has long been the only chance of
      avoiding amputation for arteritic patients. Its field of application has shifted
      as reconstructive surgery and medical therapy made progress, and it is no longer
      the only solution and has more precise indications. Proper evaluation of its
      chances of success according to the individual situations allows establishing its
      potential and limitations. This simple procedure, entailing no risk for the
      future, deserves remaining among the available means for the treatment of
      arteritis, despite its age.

PMID- 1344787
TI  - [Patelloplasty for extensive lesions of the patellar cartilage].
AB  - We have been able to review 100 cases of patelloplasty for extensive lesion of
      the patellar cartilage with an average follow up of 5 years. The technic for the
      procedure is described. The study of the results (64% of good and very good
      results) allow us the emphasize the criteria for best indications and technic. We
      prefer this technic to patellectomy or femoro-patellar prothesis in the cases of
      symptomatic degenerative arthrites with patellar excentration with special
      mention on the fact that it does not cut bridge to further procedure on the knee.

PMID- 1344788
TI  - [Laparoscopic cholecystectomy. Apropos of 450 cases].
AB  - 450 successive celioscopic cholecystectomies (May, 1990-April, 1992) are reported
      for 312 cases of uncomplicated gallstone (69%) operated electively and 138 cases
      operated in emergency, including 120 cases of acute cholecystitis, 17 cases of
      biliary pancreatitis and 1 case of angiocholitis. Immediate conversion into
      laparotomy was required in 10 cases (2.2%) either for technical reasons (1.1%) or
      because of lithiasis of the common bile duct (1.1%). The stay in hospital lasted
      an average of 2.2% days for elective admission and 3.3 days for emergent
      admission. The average operating time was 65 minutes (75 minutes until May, 1991,
      and 55 minutes between May, 1991 and April, 1992). Preoperative retrograde
      cholangiography was performed in 67 cases and intraoperative cholangiography in
      16 cases. Second surgery was required for suture in one case because of
      cholerrhagia in a secondary duct of the gallbladder bed. This cholerrhagia would
      not have been amenable to simple aspiration. One patient (0.2%) died of
      myocardial infarction at D + 10. Complications include 4 cases of pulmonary
      embolism, 3 cases of cystic biliary fistula without second surgery and 4 cases of
      umbilical hernia. A more peculiar case is that of a patient admitted 5 months
      after surgery for gangrenous acute cholecystitis. This patient was admitted for
      fever and epigrastric pain. He had a very low-flow duodenocutaneous fistula of
      uncertain origin. This patient was not operated again. This may not be a
      complication connected to celioscopic surgery. Celioscopic cholecystectomy is
      superseding conventional cholecystectomy. Surgeons' efforts should strive at
      eliminating operative errors, reducing postoperative morbidity, improving
      techniques and instruments, teaching celioscopic surgery and extending its
      indications to other intraabdominal operations.

PMID- 1344789
TI  - [Right and left laparoscopic colectomy. Apropos of 10 cases].
AB  - Ten successive cases of celioscopic colectomy are reported (5 right and 5 left
      colons). Colectomies were made for diverticular disease in 6 case and for cancer
      in the remaining cases. The patients ages range from 52 to 80 years, with an
      average of 72 years. The average duration of surgery is 92 minutes. The stay in
      hospital lasted from 5 to 7 days with an average of 6 days. All patients resumed
      fluid feeding on the 3rd postoperative day and solid feeding on the 4th to 6th
      day. None of them received analgesics later than 48 hours postoperatively. There
      was no mortality. Only one complication was noted in the form of urinary
      retention. In our opinion, colectomy with celioscopic video surgery currently has
      a definite role to play and, owing to technical and instrumental progress,
      colectomy can be performed without complementary laparotomy, at least for the
      left colon.

PMID- 1344790
TI  - [Cancer of the cardia. Prognostic factors and treatment].
AB  - Pronostic of carcinoma of the esogastric junction is worsened by the potential
      two-way route of spread in case of lymph node metastasis: mediastinum and
      abdomen. During the last 10 years the authors observed 71 cases of adenocarcinoma
      of the gastric cardia, including 7 cases of linitis plastica. Histopathologic and
      clinical follow-up data are presented. The aims of the study were to evaluate
      prognostic factors and to define the best surgical treatment. There were mainly
      elderly patients with a poor physical status. Ten patients did not undergo
      surgery (14%). Among 57 patients undergoing radial resection (80.3%), total
      gastrectomy and upper polar esogastrectomy were performed in respectively 29 and
      28 cases. The carcinomas were truly located to the gastric cardia in only 37
      cases (65%). Operative mortality was 12.3%, not depending of the surgical
      technique. All patients five-year survival rate was 10.2%, improving to 15% in
      case of curative resection. The value of lymph node metastasis (80.7% of the
      patients) as a prognostic factor depended of the proximal or distal localization
      of the nodes. A positive surgical margin (15.7% of the patients) was a poor
      prognostic factor with a 6.9 months mean survival. The authors conclude that an
      aggressive surgical approach is worthwhile, because of the carcinoma invasion
      (nodes, margin), but not always possible (poor physical status).

PMID- 1344791
TI  - [Carpal tunnel syndrome in hemodialysed patients. Analysis of 110 surgically
      treated cases].
AB  - The retrospective study of this homogeneous series of 110 carpal tunnel syndromes
      in 70 patients on hemodialysis shows the usual severity of symptoms (right thenar
      amyotrophy in 56% of cases, advanced nerve lesions in 66%). Synovitis plays a
      major role, as demonstrated by the frequency of clicking fingers (45%), and
      requires synovectomy that allows thoroughly exploring the carpal tunnel and
      removing a highly aggressive element against tendons. In this study, fisculae do
      not seem to have the generally admitted importance, but it requires surgical
      caution. Two thirds of patients were followed up for an average of 3 years. Apart
      from 3 recurrences, the control of pain is good but sensorimotor recovery is long
      and often incomplete, which is in favor of earlier surgery.

PMID- 1344792
TI  - [Surgical repair of primary or recurrent inguinal hernia by prosthesis and
      polypropylene plug].
AB  - This paper reports about experience with the cure of 2,000 primary hernia by the
      insertion of a patch, and of 1,400 recurrent hernias with obturation and a plug.
      All operations were performed under local anesthesia and with short
      hospitalization. There was almost no recurrence (2/2,000) of primary hernias, and
      only 1% for recurred hernias.

PMID- 1344793
TI  - [Experimental heterotopic transplantation of the liver with anastomosis of the
      portal vein to the distal end of the splenic vein].
AB  - A model of heterotopic liver transplantation had been studied. The graft was laid
      under the recipient liver and the portal blood flow was supplied by anastomosis
      with the distal part of the splenic vein. Both liver can then receive portal
      blood through two parallel portal circulation. Liver function of transplant was
      satisfactory at three months after transplantation. Their had been no alteration
      of the recipient liver during the same period.

PMID- 1344794
TI  - [Effect of chronic electric stimulation on colonic motricity. An experimental
      model. Results].
AB  - The study of direct electrical stimulation of the colon in 10 dogs allowed
      establishing a significant decrease in motor activity at the level of the
      stimulated segment, a nonsignificant decrease upstream and a significant increase
      downstream. The mechanism of intestinal response to stimulation remains
      hypothetic: there probably is a local release of neuromediators.

PMID- 1344795
TI  - [Calculation of optimized and individualized hip prosthesis. A study of
      feasibility].
AB  - As logical consequence of a series of basic research studies on human femoral
      bones with unipodal support and under static stress, performed with
      physicomathematic modelling methods (finite-elements method) then confirmed by
      direct visualization of deformations resulting from such stress using holographic
      interferometry, the authors have worked on the definition of an optimized and
      individualized hip prosthesis. Thick CT sections digitized with a table and
      entered into a specially programmed computer allowed three-dimensional modelling
      of the femur as a volume, i.e. with its external contour and its medullary canal,
      and therefore of the implantable space. The prosthesis was then defined taking a
      number of hypotheses into account: necessity to regularize cortical bone spicules
      inside spongious bone, which are so often present opposite the rough line,
      partial machining at the level of the calcar, reduced tail length, presence or
      absence of collar. Thus an optimized and individualized prosthesis was defined. A
      prototype corresponding to a given femoral bone could then have been produced.
      However, the authors found it preferable to use simulation with computer
      synthetic images to check easy insertion and removal.

PMID- 1344796
TI  - [The admission of Dr. Avedis Donabedian as an Honorary Member].

PMID- 1344798
TI  - [Dermatosis cinecienta. A clinico-pathological study of 20 patients (1989-1990)].
AB  - Ashen dermatosis (D.C.), or dyschromic perstans erythema, is a chronic
      dermatosis, which is asymptomatic and practically exclusive in Latin-American
      countries. Its clinical characteristics have been well defined (blue-gray
      patches), as well as its nonspecific histopathologic patterns; its etiology is
      unknown. This paper studies 20 patients suffering from ashen dermatitis. There
      was a majority of female patients, the dermatosis was disseminated, bilateral and
      symmetric. It is different from pigmented lichen although the histopathologic
      patterns is similar.

PMID- 1344797
TI  - [The molecular diagnosis of hereditary diseases. In memoriam Dr. Eduardo Aguirre
      Pequeno].
AB  - Accordingly, we have established in our unit a DNA diagnosis laboratory and have
      started molecular genetics and epidemiological studies of several inherited
      diseases. We have started with cystic fibrosis, muscular dystrophy and hemophilia
      A. We practice the molecular diagnosis with both, Southern transfer and the
      polymerase chain reaction, using either direct (detection of mutations) or
      indirect (restriction fragment length polymorphisms) approaches. With the studies
      we have so far carried out, we have been able to provide genetic counseling and
      gained valuable information on the type and frequency of mutation associated to
      these diseases in our region.

PMID- 1344799
TI  - [Magnetic resonance in the staging of renal-cell cancer. The experience at the
      Hospital Central Militar].

PMID- 1344800
TI  - [Distraction as a stimulus of bone formation].
AB  - In orthopaedics limb length discrepancy and bone lost from infection are more
      frequent and difficult to resolve at the moment G. Ilizarov showed new bone
      formation with slow distraction stimulation in a well vascularization an rigidly
      fixed bone. Good patient selection, surgical technique, complete post-operative
      care and patient collaboration are necessary to get excellent or good results.
      This paper involves 50 patients, 39 with limb lengthening and 11 with infection
      and bone loss. We obtained excellent and good results in 37 cases of lengthening
      and 10 in the second one. At the moment the complications with external fixators
      may be used and we advised their use.

PMID- 1344801
TI  - [The present frontiers of human genetics].

PMID- 1344802
TI  - [The history of the first "voluntary" oral hydration center in Mexico (1959)].
AB  - There are some historic facts about the "First Center for Voluntary Oral
      Rehydration" begun 1959 at Hospital Infantil de Mexico (Children's Hospital) was
      clearly demonstrated useful, 508 infants with diarrhea were treated. 90.94% were
      cured and dehydration corrected. Antibiotics were not much useful. Oral
      rehydration is considered the method of choice to begin treatment of the patient
      with gastroenteritis.

PMID- 1344804
TI  - [Mozart, myths and realities].

PMID- 1344803
TI  - [Mozart's clinical history].

PMID- 1344805
TI  - [The population and the challenges of social development].

PMID- 1344806
TI  - [The physician and the modernization of medicine].

PMID- 1344807
TI  - Proceedings of the XIX annual meeting on Basic Research in Chagas' disease and
      the VIII meeting of the Brazilian Society of Protozoology. Caxambu, November 10
      13, 1993. Abstracts.

PMID- 1344808
TI  - An epidemic of non-Hodgkin's lymphoma: comments on time trends, possible
      etiologies, and the role of pathology.

PMID- 1344809
TI  - Histopathology of community acquired chronic hepatitis C. The Sentinel Counties
      Chronic Non-A, Non-B Hepatitis Study Team.
AB  - As part of a study of community-acquired non-A, non-B hepatitis, liver biopsy
      specimens of 29 anti-HCV positive and four anti-HCV negative patients were
      evaluated in order to characterize the histopathologic changes of chronic
      hepatitis C. Liver biopsies were performed 6 to 46 mo after onset of the disease
      and repeat biopsies were obtained in 10 anti-HCV positive patients. The
      histologic diagnoses were chronic persistent hepatitis (45%), chronic active
      hepatitis (35%), and chronic lobular hepatitis (21%). Irrespective of the tissue
      diagnosis, the majority of the patients showed characteristic histologic
      abnormalities in the liver, particularly damage of the small and medium-sized
      bile ducts (76%), lymphoid aggregates in portal tracts (45%), enlarged
      macrophages (48%), and steatosis (31%). In 59% of the patients, two or more of
      these histologic abnormalities were combined. Similar histologic changes have
      previously been observed in non-A, non-B hepatitis, but only uncommonly in
      hepatitis A or hepatitis B. We conclude that the histopathologic findings in
      chronic hepatitis C are highly characteristic, although not
      pathognomonic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1344810
TI  - Lymphoid interstitial pneumonia not associated with HIV infection: role of
      Epstein-Barr virus.
AB  - The polymerase chain reaction (PCR) method was used to determine the presence of
      Epstein-Barr virus sequences in seven cases of pulmonary lymphoid interstitial
      pneumonia not associated with HIV infection. Evidence of Epstein-Barr virus
      genome was found in three of six cases in which beta-globin gene, used as an
      internal control for the integrity and amplifiability of the tissue DNA, could be
      detected. These results suggest that Epstein-Barr virus infection is not always
      required for the development of lymphoid interstitial pneumonia.

PMID- 1344811
TI  - Ki-1 (CD30) expression in differentiation of lymphomatoid papulosis from
      arthropod bite reactions.
AB  - Lymphomatoid papulosis (LP) is an uncommon cutaneous T-cell lymphoproliferative
      disorder that can mimic arthropod bite reactions clinically and histologically.
      Erythematous, crusted papules and nodules occur mainly on extremities of young
      adults and, when biopsied, display a superficial and deep perivascular infiltrate
      characterized by atypical lymphocytes and scattered eosinophils. Arthropod bite
      reactions may show an identical histologic pattern. It has been suggested that up
      to 10% of patients with LP will eventually develop lymphoma. We examined biopsies
      from 10 cases of LP and six cases of arthropod bite reactions diagnosed by
      clinical history and prolonged follow-up, with BerH2, an antibody directed
      against the Ki-1 antigen (CD30) and found it to be useful in helping distinguish
      between the two entities. All cases of LP examined showed scattered Ki-1-positive
      large, atypical lymphocytes in the dermis. In the arthropod bite reactions, there
      was virtually no staining with BerH2 antibody. This suggests that the abnormal
      activated T-cells, which comprise the cellular infiltrate in LP, are not present
      in arthropod bite reactions.

PMID- 1344812
TI  - "Signet Ring" sinus histiocytosis mimicking metastatic adenocarcinoma: report of
      two cases with immunohistochemical and ultrastructural study.
AB  - The axillary lymph nodes from two patients with invasive breast carcinoma showed
      "signet ring" histiocytosis with sinusoidal distribution of cells having
      prominent cytoplasmic vacuolization which simulated metastatic adenocarcinoma.
      Immunohistochemical studies confirmed the histiocytic nature of the signet ring
      cells and eliminated the possibility of metastatic adenocarcinoma. Electron
      microscopy in one case revealed lipid within the cytoplasmic vacuoles. The
      etiology of this reactive change is unknown; however, a history of previous
      surgery involving the chest wall may be causally related with disruption of
      adipose tissue. Prior to ipsilateral mastectomy both patients had undergone a
      contralateral mastectomy for mammary carcinoma. Signet ring sinus histiocytosis
      is a reactive sinusoidal proliferation that can mimic metastatic carcinoma, but
      close inspection will usually reveal the histiocytic nature of the cells.

PMID- 1344813
TI  - Detection of hepatitis C virus RNA sequences by polymerase chain reaction in
      fixed liver tissue.
AB  - Currently, the most reliable method for the diagnosis of hepatitis C virus (HCV)
      infection is the detection of viral sequences by the reverse transcription double
      polymerase chain reaction (RT/PCR) in serum or liver samples. We demonstrate here
      that noncoding region sequences (NT) of HCV were amplifiable by RT/PCR in
      guanidinium extracts of formalin-fixed (for 6 to 48 h), paraffin-embedded liver
      sections of patients with chronic hepatitis C. In contrast, core and
      nonstructural region sequences of HCV were not detectable in fixed tissues by PCR
      amplification. Boiling of routinely processed tissue sections in water containing
      Chelex-100, a method for extraction of amplifiable hepatitis B virus DNA, was not
      successful. The amount of nucleic acid extracts from fixed liver sections needed
      for amplification of NT region sequences was over 1000 times larger than that of
      extracts from frozen tissue. This method will be useful for diagnostic and
      investigative studies of HCV infection.

PMID- 1344814
TI  - DNA ploidy and karyotype in recurrent and metastatic soft tissue sarcomas.
AB  - To study mechanisms involved in evolution of soft tissue sarcomas, we compared
      DNA ploidy and karyotypes at different stages of their disease in two patients
      with myxoid liposarcomas (MLS), one with a fibrosarcoma (FS), and two with
      rhabdomyosarcomas (RMS). None of the MLS samples revealed clearcut histologic
      changes in later samples as compared to their primaries, and the DNA ploidy in
      all samples was diploid. In one patient karyotypes at four different times during
      the 19 yr of his disease all revealed a t(11;12) (p15;q13), but additional clonal
      chromosomal abnormalities occurred only in later recurrences. In another patient
      the karyotypes obtained in the 26th and 28th yr of his disease were similar and
      included the t(12;16) (q13;p11), characteristic of MLS. A comparison with
      karyotypes of six other MLS patients at different disease stages suggests that
      the presence of a t(12;16) may correlate with less aggressive clinical behavior.
      The histology of the FS remained low-grade and the DNA ploidy diploid. The
      karyotype, however, showed evolution. In both MLS and FS, chromosomal changes
      thus seem to be a more sensitive marker for tumor progression than histologic
      changes or DNA ploidy. In one embryonal RMS, karyotypes obtained 7 and 11 yr
      after the primary diagnosis were different but clearly had a common "progenitor."
      In one alveolar RMS, the primary and the synchronous lung and lymph node
      metastases all revealed a t(2;13). The findings in RMS suggest that
      polyploidization is an early event in tumor evolution, especially in the alveolar
      subtype, which may be followed by additional chromosomal changes. In addition,
      DNA ploidy was measured in eight other RMSs. Among the RMSs the embryonal subtype
      was characterized by DNA aneuploidy, whereas three of the alveolar cases were in
      the tetraploid range and one was peridiploid. In local recurrences and in
      metastases changes in DNA index were observed in half the cases.

PMID- 1344815
TI  - Signet cell melanocytic lesions.
AB  - Malignant melanoma can produce diagnostic problems for the histopathologist
      because of its protean histologic patterns. The recently recognized signet cell
      pattern can be particularly confusing and must be distinguished from
      adenocarcinoma, tumors of vascular endothelium or adipose tissue, lymphoma, and
      epithelioid smooth muscle lesions. We report four new cases of signet cell
      melanoma and illustrate this pattern in primary as well as metastatic sites. In
      addition, we document the signet cell pattern in benign nevi for the first time,
      expanding the concept of this pattern to melanocytic cells in general. The
      differential diagnosis of signet cell melanoma and its mimics is discussed and
      the utility of immunohistochemical stains in this diagnosis is stressed.

PMID- 1344816
TI  - Morphometric quantitation of tumor necrosis in stage 1 non-small cell carcinoma
      of lung: prognostic implications.
AB  - We objectively examined the extent of tumor necrosis by computer-assisted
      morphometry in 28 patients with surgically resected Stage I non-small cell
      carcinoma of lung. Fourteen of the 28 patients were long-term survivors (mean
      survival after diagnosis 94 mo) and 14 were short-term survivors (up to 62 mo
      after diagnosis). The extent of tumor necrosis was determined by means of a
      computer assisted digitizing system. The two sample t test and the two-tailed
      Wilcoxon rank score tests were used for statistical analysis of comparison of the
      extent of tumor necrosis between the two groups of patients. This morphometric
      study showed that the extent of tumor necrosis was significantly associated to
      the probability of long-term survival, with long surviving patients having a
      lesser degree of tumor necrosis (t = 2.75, p < 0.02, 2 sample t test, two-tailed,
      df = 26). These findings reaffirm previous subjective data, derived from
      pathologist assessment of tumor necrosis, and suggest that morphometric
      evaluation of tumor necrosis may play a useful adjunct role in predicting
      prognosis of carcinoma of lung.

PMID- 1344817
TI  - p53 protein expression in transitional mucosa and adenocarcinomas of the
      colorectum.
AB  - Transitional mucosa, the nonneoplastic mucosa adjacent to colorectal
      adenocarcinomas, exhibits some morphologic and histochemical abnormalities. It is
      unclear, however, whether transitional mucosa is a preneoplastic or reactive
      phenomenon. Though normal p53 functions as a tumor suppressor, p53 gene
      alterations have been proposed as a step in malignant transformation, and
      aberrant p53 protein expression has been described in a high percentage of
      colonic adenocarcinomas. Since p53 protein normally has a short half-life,
      immunohistochemical detection of the protein is considered to be evidence of
      abnormal p53 expression. We analyzed p53 protein expression immunohistochemically
      on frozen tissue samples of transitional mucosa, normal mucosa, and tumor from 20
      cases. In all 20 cases the transitional mucosa and normal mucosa failed to
      express p53, while 13 of 20 adenocarcinomas showed positive immunoreactivity
      characterized by intense nuclear staining. There was no correlation between tumor
      stage and p53 expression. The absence of staining for p53 protein in TM does not
      support the theory that transitional mucosa is a preneoplastic phenomenon.

PMID- 1344818
TI  - Patterns of basement membrane laminin distribution in nonneoplastic and
      neoplastic thyroid tissue.
AB  - Laminin, a major basement membrane component, is typically absent or partially
      lost around the epithelial elements of most invasive carcinomas. To evaluate the
      distribution of laminin in both primary and metastatic thyroid tumors, we studied
      14 benign thyroid lesions (eight adenomas, two Graves' disease, two Hashimoto's
      thyroiditis, one adenomatous hyperplasia, one nodular goiter), 20 carcinomas
      (seven papillary, six tall cell variant, four follicular, three Hurthle), and
      eight metastases (five tall cell variant, three follicular) utilizing a
      polyclonal antibody against highly purified, nidogen-free laminin. All benign
      lesions showed positive, linear immunostaining along basement membranes. Partial
      loss or absence of laminin was seen in the solid areas of all types of thyroid
      carcinomas examined; well-differentiated papillary and follicular tumors, as well
      as papillary and follicular areas of more poorly differentiated neoplasms,
      maintained linear laminin immunostaining in the papillary cores beneath the
      epithelial cells and around follicles. A similar correlation between laminin
      deposition and architectural organization was seen in metastatic lesions. Hurthle
      cell carcinomas had a unique fragmented, pericellular immunostaining pattern
      around individual tumor cells, suggesting uncontrolled laminin synthesis. Our
      findings suggest that preservation of laminin production in thyroid tumors
      reflects their degree of differentiation and that absence of laminin correlates
      with lack of structural organization rather than reflecting invasive and
      metastatic potential.

PMID- 1344819
TI  - A fetal testis with intratubular germ cell neoplasia (ITGCN).
AB  - A fetal testis with abnormal germ cells similar to the cells of intratubular germ
      cell neoplasia (ITGCN) or so-called carcinoma in situ is presented. Elective
      abortion was performed in week 18 of the pregnancy of a 26-yr-old woman, because
      of 21 trisomy (Down's syndrome) at amniocentesis. At microscopical examination
      abnormal germ cells were found, similar to those occurring in the adult testis
      and with the same distribution as those described in ITGCN in children with
      dysgenetic gonads and with androgen insensitivity syndrome. PAS positivity and
      placental-like alkaline phosphatase (PLAP) was demonstrated in the abnormal germ
      cells. The finding indicates that the first event of germ cell tumor oncogenesis
      may take place before birth, in utero or even before. The occurrence of ITGCN in
      Down's syndrome has not been reported previously but is likely to occur, as there
      is evidence that these patients have increased risk of developing germ cell
      tumors.

PMID- 1344820
TI  - Characterization of the topography of Epstein-Barr virus infection in human
      immunodeficiency virus-associated lymphoid tissues.
AB  - A highly sensitive in situ hybridization methodology for Epstein-Barr virus (EBV)
      RNA was used to determine the topography of EBV infection in 16 cases of human
      immunodeficiency virus-associated lymphoid tissues. Four lymphomas, 11 persistent
      generalized lymphadenopathy (PGL) lymph nodes, and one lymphoepithelial cyst were
      studied. The pattern of EBV infection was diffuse in all lymphoma cases and
      predominantly interfollicular in PGL nodes. No discernable pattern of infection
      was present in the lymphoepithelial cyst. Germinal center cells were also
      infected in seven of the PGL cases, and this pattern predominated in one case.
      Double labeling immunohistochemistry/in situ hybridization studies on four cases
      of PGL indicated that the EBV infection was primarily involving B-lymphocytes,
      but rare infected T-lymphocytes were also identified. These studies further
      clarify the pattern and cellular site of EBV infection in human immunodeficiency
      virus-related lymphoid disease.

PMID- 1344821
TI  - Recommendations on quality control and quality assurance in surgical pathology
      and autopsy pathology. The Association of Directors of Anatomic and Surgical
      Pathology.

PMID- 1344822
TI  - Enzymatic treatments on paraffin blocks for DNA flow cytometry.
AB  - The Hedley method for DNA ploidy analysis on paraffin-embedded tissue allows
      retrospective studies of large numbers of common and rare tumors for which
      treatment, progression, and outcome are known. However, the technique is
      cumbersome and has many variables, only some of which can be controlled at the
      time of laboratory analysis. We performed DNA ploidy analyses on two blocks from
      two islet cell tumors and on five blocks from two colon carcinomas. Sections of
      50-microns thickness were deparaffinized in xylene, rehydrated in graded alcohols
      and in distilled water, and disaggregated with various enzymatic treatments:
      0.05% pepsin (30 and 90 min), 0.5% pepsin (30 and 90 min), 0.05% protease (60
      min), and 0.1% protease (60 min). The cell suspensions obtained were filtered,
      washed in PBS, and visually evaluated in a hemocytometer. Nuclei were treated
      with RNAse (0.1%) and stained with 50 micrograms/ml propidium iodide. Results
      were evaluated with the following criteria: (a) recovery of DNA aneuploid and/or
      G2M cells (cell-cycle analysis and visual evaluation); (b) coefficient of
      variation of the major peak (DNA diploid or DNA aneuploid depending on the case);
      (c) amount of debris (background events and visual evaluation); (d) mean channel
      for the G0G1 peak; (e) event rate; and (f) G2M/G0G1 ratio. The best results were
      observed with 0.05% protease when there was tissue necrosis and hence cell
      fragility, with 0.1% protease when there was significant tissue fibrosis, and
      with 0.05% pepsin (90 min) when there were intact cellular specimens without
      fibrous entrapment. The original procedure using 0.5% pepsin for 30 min produced
      less cell recovery, and histogram quality similar to or worse than these
      modifications in all cases studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1344823
TI  - Antigen diffusion and uptake: a caveat in immunohistochemical interpretation.
AB  - Thyroglobulin was demonstrated by monoclonal immunohistochemistry in the
      cytoplasm of renal cell carcinoma cells metastatic to the thyroid gland. This was
      attributed to release of thyroglobulin from injured native thyroid with diffusion
      and uptake by tumor cells. Previously reported cases of this process in tumors in
      thyroid, skeletal muscle, and lymphoid tissue are reviewed. Interpretation of the
      significance of demonstrated antigens in tumor cells, especially those that are
      constituents of invaded native tissues and only focally present, should be
      interpreted with caution and in conjunction with other histologic evidence.

PMID- 1344824
TI  - Research by pathologists not funded by external grant agencies: a success story.
AB  - The paradigm of pathology research as an endeavor among grant-funded principal
      investigators resulting in first-author publications is unsupported by
      quantitative examination of author profiles extracted from the scientific
      literature. Publications in six pathology journals (Modern Pathology, American
      Journal of Surgical Pathology, Human Pathology, Acta Cytologica, Archives of
      Pathology and Laboratory Medicine, and American Journal of Clinical Pathology)
      and three general science journals (Science, New England Journal of Medicine, and
      Proceedings of the U.S. National Academy of Sciences) were reviewed. Twenty
      articles per journal from each of three years (1987, 1989, and 1991) were
      examined (a total of 520 articles). Of these, 295 articles were first-authored by
      a member of a department of pathology. Of the 295 articles first-authored by a
      member of a pathology department, 47 (16%) articles listed competitive grant
      support. Of the grant-supported articles, 20 articles listed NIH support, but
      only four had an NIH-supported principle investigator as the first author of the
      article. Unfunded research represented the vast majority (84%) of work produced
      by pathologists. A review of the ISI Citation Index showed that those articles
      written by funded pathologists averaged 8.7 (S.D. 7.8) citations per article,
      compared to 10.4 (S.D. 12.1) citations per article for unfunded pathologists.
      Results suggest that unfunded research accounts for the majority of pathology
      research activity as well as their resulting literature citations.

PMID- 1344825
TI  - Excessive collagen formation in fibrolamellar carcinoma of the liver: a
      morphological and biochemical study.
AB  - We have studied the excessive deposition of extracellular matrix in a patient
      with fibrolamellar carcinoma of the liver. The collagen matrix was predominantly
      composed of collagens I, III, and V. Since specific mRNAs for collagens I and III
      were detected by in situ hybridization, we also provide evidence that the
      fibroblastoid stromal cells were the major source of this collagen. Occasionally,
      also tumor cells could be shown to express collagen III-mRNA. Furthermore, some
      tumor cells showed positive signals for TGF-beta 1, while isolated stromal cells
      expressed interleukin-6. This cytokine expression may probably be related to the
      altered control of collagen gene expression.

PMID- 1344826
TI  - Bilateral massive ovarian leiomyomata in a young woman: a case report with review
      of the literature.
AB  - We report a case of ovarian leiomyomata, bilateral and massive, in a 21-yr-old
      woman. Primary leiomyoma of the ovary is a very rare tumor and is usually small,
      unilateral, and concomitant with uterine leiomyomata. To our knowledge, this is
      the first report in the English literature of bilateral ovarian leiomyomata. We
      document the smooth muscle origin of the tumors with immunohistochemical studies
      that show appropriate staining with antibodies to vimentin, muscle specific
      actin, desmin, smooth muscle actin, and collagen type IV. The available
      literature is reviewed. The characteristics of both typical and atypical ovarian
      leiomyoma and theories of its origin are discussed.

PMID- 1344827
TI  - [Value of early cerebral angiography in cerebral infarctions in young subjects].

PMID- 1344829
TI  - [Dominant polycystic renal disease. Study of 105 cases].
AB  - The study concerns 105 cases of dominant polycystic kidney disease. Affected
      relatives were observed in 65% of patients. The clinical features that leads to
      diagnosis were lumbar pain in 37.5% of cases, renal failure in 24.6% of cases and
      hypertension in 15.1% of cases. Hypertension was observed in 46.7% of cases and
      it seems that its onset is independent of chronic renal failure. Its frequency is
      of 55.1% when only kidneys were affected and of 21.4% when the liver was affected
      too. The progression of chronic renal failure is influenced by hypertension.

PMID- 1344828
TI  - [Contribution of 99mTc MAG3 in hypertension in an elderly subject with renal
      artery thrombosis].
AB  - To ascertain the responsibility of renal artery thrombosis for the genesis of
      arterial hypertension, the methods available are not sufficiently sensitive and
      reproducible, and the residual revascularization maintained by a vicarious
      arterial network is not easy to demonstrate. Renal scintigraphy with technetium
      99m-labelled mercaptoacetyltriglycine (MAG3) was performed in 4 old and severely
      hypertensive male patients with chronic thrombosis of one renal artery. With this
      tracer the thrombotic kidney was detected lately and weakly at the vascular and
      nephrographic stages. When the functions of both kidneys were compared, that of
      the affected kidney was always estimated at less than 5%. At the excretory stage
      a residual activity could be detected in the kidney with renal artery thrombosis.
      Owing to the specific biophysical behaviour of the tracer, MAG3 scintigraphy
      coupled with arteriography and assays of plasma renin activity in the veins
      contribute to the decision concerning nephrectomy.

PMID- 1344830
TI  - [Malignant lymphoma of the testicles].
AB  - Between January 1980 and January 1990, a tumour of the testis in 12 of our
      patients was found to be a non-Hodgkin's malignant lymphoma (NHL). Age varied
      from 16 to 83 years, with 9 of them aged over 50. In 7 cases the pretherapeutic
      evaluation disclosed one or more other visceral sites of the tumour, and in 6
      cases the tumoral diameter reached or exceeded 10 cm. Staging according to the
      Ann Arbor classification was: IE: 3 cases; IIE: 1 case and IV: 8 cases. The
      histological type assessed according to the international classification was:
      lymphoblastic (2 cases), small cell non cleaved of Burkitt's type (1 case),
      immunoblastic (2 cases), large cell diffuse (3 cases), mixed diffuse (3 cases),
      small lymphocyte diffuse (1 case) and unclassifiable (1 case). Seven patients
      underwent orchiectomy which, in 3 of them, was not followed by any other
      treatment. Nine patients were put on polychemotherapy which was intensive in 6
      cases. Median survival was 30 months. Four patients, all treated intensively, are
      now in persistent complete first remission. This study confirms that NHL of the
      testis is rare and its malignancy in almost every case is either high or
      intermediate grade NHL. It occurs predominantly in elderly men. Advance
      prognostic factors are often present at diagnosis. However, the advent of
      intensive polychemotherapy seems to have transformed the course of the disease as
      well as that of other aggressive NHL's in more common sites.

PMID- 1344831
TI  - [Omeprazole and liver functions].
AB  - Omeprazole is the first of a new class of drugs (proton pump blockers) approved
      in the United States and in Europe for its high efficiency as an inhibitor of
      gastric acid secretion. Omeprazole is a drug for short term use in patients with
      acid-peptic disease. A limited prevalence of hepatotoxic effects is reported by
      some authors (transitory rise in serum aminotransferase level) and it may be
      prescribed in patients with chronic liver disease although slower metabolism and
      greater bioavailability are observed. Omeprazole interacts with the cytochrome P
      450 system in the liver: inhibition of several liver mono-oxygenases activities
      (inhibitory effect on diazepam, phenytoin and R-warfarin metabolism with
      prolonged elimination); induction of P-450 (IA1 and IA2) enzymes that may
      potentiate the hepatotoxic effect of phenacetin and acetaminophen or increase the
      tumorigenic effect of chemical carcinogens (polycyclic aromatic hydrocarbons,
      arylamines, aflatoxin). This latter concern is unfounded as based on a false
      extrapolation from the results of in vitro studies to those of in vivo
      situations. However, although omeprazole has proved to be remarkably free of side
      effects, postmarketing surveillance is recommended for potential interaction with
      other drugs that are known to be metabolized by the same liver enzymes.

PMID- 1344832
TI  - [Abdominopelvic actinomycosis in pseudo-tumoral form: diagnosis by
      ultrasonography-guided biopsy].
AB  - The authors report a case of abdominopelvic actinomycosis, a rare bacterial
      infection. This case is exceptional for its clinical tumoral expression with
      fistulization through the skin, and for its rapid diagnosis by ultrasonically
      guided needle biopsy. The clinical, bacteriological, histological and therapeutic
      aspects of actinomycosis are detailed.

PMID- 1344833
TI  - [Right cardiac insufficiency disclosing systemic mastocytosis].
AB  - The authors report the case of a 54-year old woman presenting with right cardiac
      failure in whom the diagnosis of contemporaneous cutaneous-systemic mast cell
      disease was made. The cardiac symptoms regressed concomitantly with the vasomotor
      manifestations of the mast cell disease. Following a review of the principal mast
      cell mediators, the cardiovascular manifestations of the disease are studied and
      pathogenetic hypotheses are being put forward.

PMID- 1344834
TI  - [Jejunal perforation by cholesterol embolus: a case treated surgically].
AB  - A case of ischaemic jejunal perforation which could be attributed to mesenteric
      cholesterol emboli is reported. The jejunal pathology had been preceded by other,
      more classical sites of systemic cholesterol embolization that occurred
      immediately after arterial catheterization in this male patient with aneurysm of
      the abdominal aorta. Emergency segmental resection of the jejunum was performed
      with satisfactory immediate results. Histological examination of the operative
      specimen confirmed that the perforation was caused by cholesterol emboli.
      Cholesterol embolization of the intestine may have various clinical consequences
      which are reviewed by the authors.

PMID- 1344835
TI  - [Acute ischemia of an arm manifesting Buerger's disease. Predisposing role of
      anorexia nervosa].
AB  - Peripheral vasomotor disorders, notably acrocyanosis, are frequent in anorexia
      nervosa, but ischaemic accidents are unknown. We report the case of a 32-year-old
      woman with a 10-year history of anorexia nervosa, who developed acute ischaemia
      in one of her upper limbs. In this particular case several aetiological factors
      may be considered: Buerger's disease, of course, as the patient smoked and had an
      abnormal arteriography, but also hypercholesterolaemia, thrombocytosis and
      disorders of platelet aggregation.

PMID- 1344836
TI  - [Bony involvement of the calcaneum in sarcoidosis. A case report].
AB  - Bone lesions of sarcoidosis occur in 10 to 15% of the cases, most often involving
      the extremities. These frequently corticosteroid-dependent lesions worsen the
      prognosis of the disease. We report a case of sarcoidosis of 14 years duration in
      a 58-year old woman who presented with a bone lesion strictly localized to the
      calcaneum. To our knowledge, such lesion has not previously been reported.

PMID- 1344837
TI  - [Ptosis and asthenia manifesting a mitochondrial myopathy].
AB  - We report a case of mitochondrial myopathy discovered in a 55-year old woman who
      was being investigated for the cause of her asthenia. Physical examination showed
      ptosis of the upper eyelid and proximal muscle deficit. Histological examination
      of a muscle biopsy disclosed rare fibres with mitochondrial aggregates.
      Biochemical exploration of muscle tissue revealed a double enzyme deficit
      involving complexes I and IV of the respiratory chain. Clinical improvement was
      obtained after the patient was put on coenzyme Q10. We conclude that a diagnosis
      of mitochondrial myopathy must be considered in patients, including middle-aged
      adults, presenting with muscular asthenia.

PMID- 1344838
TI  - [Acute interstitial nephritis with uveitis. A case report].
AB  - Dobrin et al described in 1975 the first case report with acute renal failure due
      to tubulo-interstitial nephritis accompanied by uveitis and an inflammatory
      syndrome. The young adults are frequently involved and the complete resolution is
      usually obtained after corticosteroid treatment; this contrasts with the tendency
      towards relapse of the uveitis. The etiology and the pathogenesis of this
      syndrome remain unknown. We report the case of a woman which the renal function
      was incompletely reversible with corticosteroids.

PMID- 1344839
TI  - [Benefits of corticosteroids in the treatment of Horton's disease and rhizomelic
      pseudopolyarthritis: advantages and inconveniences. A meta-analysis].
AB  - Although corticosteroid treatment is clearly beneficial to patients with temporal
      arteritis, its exact risk/benefit ratio in these old and side effects-prone
      patients is unknown. We have thus surveyed that available French and English
      literature, in order to pool the published series and to evaluate the iatrogenic
      potential of corticosteroids in this situation. We selected 11 series, yielding a
      total of 1008 patients. A treatment failure resulted in the death of the patient
      in five cases. Twenty-seven patients became blind, but only 2 under treatment.
      The side-effects involved 29% of the patients and are responsible of 29 deaths
      (2.9%): osteoporosis was the main problem, followed by femoral head necrosis and
      muscle wasting. Gastroduodenal ulcers were uncommon and generally benign; sigmoid
      colon diverticulitis was infrequent but dangerous; some infectious complications
      were noted (herpes zoster, tuberculosis, etc...); high blood pressure and
      diabetes were common problems. Psychiatric side-effects were rare. Thus, the
      unwanted effects of corticosteroids in the treatment of temporal arteritis are
      relatively infrequent and generally not severe, except osteoporosis. They should
      be systematically prevented by appropriate diet and treatments (e.g., calcium,
      potassium, and vitamin D supplements).

PMID- 1344840
TI  - [Respective prevalences and frequencies of Horton's disease and rhizomelic
      pseudopolyarthritis. Epidemiological study in the Loire-Atlantic department using
      a general practice research network (RESOMED 44)].
AB  - Using a research network of general practitioners (Resomed 44) representing the
      20th of all GP's in the Loire Atlantique region and distributed at random
      according to district, age and sex made it possible to evaluate the respective
      prevalences of temporal arteritis (TA) and polymyalgia rheumatica (PMR) in all
      the systemic immune diseases listed. Among these diseases, rheumatoid arthritis
      was the most frequent (35.39%). TA (18.8%) and PMR (18.54%) had about the same
      prevalence. For each of these diseases the year/physician prevalence was
      evaluated at 0.11, which means that the probability for each GP to see 1 TA and 1
      RP at once in 10 years. At the time of the survey, 52.9% of TA patients and 78.8%
      of PMR patients were surviving. GP's alone follow up more TA's and PMR's than the
      other systemic immune diseases.

PMID- 1344841
TI  - [Abdomino-crural contracture manifesting an adrenal gland insufficiency of high
      origin: a new case report].

PMID- 1344842
TI  - [A new case report of J-Baltimore hemoglobinopathy in a diabetic caucasian].

PMID- 1344843
TI  - [Muscular toxicity from clofibrate treatment in hypopituitarism: role of SIADH].

PMID- 1344844
TI  - [Treatment of scapula alata with a new surgical technique].
AB  - By analysing the various surgical procedures used in the management of scapula
      alata, the author describes a personal technique where scapula is fixed to the
      7th rib with the shot palmar tendon. For the stabilisation of the scapula, its
      inferior angle introduced under the great dorsal is sutured with strong catgut,
      the needle entering from under the depth of muscle and emerging on its posterior
      aspect where catgut ends are knotted.

PMID- 1344845
TI  - Management of perineal impalement injuries.
AB  - Between 1975 and 1990, 18 cases of sphincter and pelvic floor injuries, of which
      7 isolated and 11 part of severe polytraumas, were treated. Thirteen cases
      benefited from primary repair. Colostomy was required in 9 cases due to the
      complexity of lesions, in other 5 cases the wounds drainage and colostomy were
      undertaken. Secondary repair was done after 2-6 months. The functional results in
      11 patients indicate a good continence in 6 of 7 cases with primary repair. The
      results of secondary repair are satisfactory.

PMID- 1344846
TI  - [The prosthetic saddle in physiognomic reconstruction of the dental-alveolar
      arches].
AB  - The investigation of 2087 patients with partially extended, subtotal and total
      edentations who presented to the Clinic of Dental Gnathoprosthetics of Iasi made
      possible the assessment of the role and importance of prosthetic saddle in the
      physiognomic restoration in such patients. By applying the modern clinical and
      technical methods of designing and making the gnathoprosthetic apparatus, the
      physiognomy of dento-alveolar arches according to actual exigencies and observing
      the dento-facial harmony can be achieved.

PMID- 1344847
TI  - [Physiognomic reconstruction of the dental arches in emergency treatment].
AB  - The gnathoprosthetic treatment in emergency is now a compulsory step in solving
      the esthetic problems raised by the affections of stomatognathic system (coronary
      lesions, edentation) localised in visible areas of dental arches. Nowadays, the
      state of stress induced by these affections can be relieved by an immediate and
      highly physiognomic treatment, a method at hand being the Scutan mask. Excellent
      technic results can be obtained by using conformators obtained by
      thermoplasticizing and vacuumating, in current use in our clinic.

PMID- 1344848
TI  - [Clinical variability in partial and extensive anodontia].
AB  - In a longitudinal study, 48 patients aged between 4.6 and 30.5 years with various
      degrees of partially extended anodontia were investigated clinically and
      paraclinically for 4 years. The changes in occlusal function in the context of
      clinical variability of partially extended anodontia will also induce, finally, a
      change in the fundamental craniomandibular relation.

PMID- 1344849
TI  - [Therapeutic means and methods in recurrent pleurisy].
AB  - During a 10-year interval (1981-1991), at the IIIrd Medical Clinic of Iasi 960
      cases with pleural effusion, of which 768 (80%) non-recurrent and 192 (20%)
      recurrent, were diagnosed. The etiology in the latter cases was malignant (40%)
      and non-malignant (60%). Proper treatment methods for limiting or suppressing the
      recurrent pleurisies proved to be imperative. Thoracocenteses cause protein and
      electrolyte depletion which aggravate the general state and hasten the
      unfavourable evolution of the etiological affection. This is the reason why
      besides the general etiopathogenic treatment, a local pathogenic treatment
      (cytostatic, anti-inflammatory) and especially pleurodesis are compulsory. The
      intrapleural administration of cortisone is efficient in the case of recurrent
      autoimmune pleural effusions but is worthless in the malignant ones. In the
      latter situation, the intrapleural cytostatic treatment should be first attempted
      and, in case of failure, the development of pleural symphysis by external
      radiotherapy or injecting talc into the pleural space should be made. In the
      terminal stage of cardiac insufficiency or liver cirrhosis with recurrent pleural
      effusion, the pleurosymphysation is not indicated; a sever edematous-ascitic
      attack may occur or become aggravated by the pleural irritative process due to
      this method.

PMID- 1344850
TI  - Etio-pathogenic views on transsexualisms (TS).
AB  - Starting from the analysis of six cases of transsexualism (TS) the authors
      performed complex investigations of all sex levels and identified primary T.S.
      (disturbances of sexual differentiation), secondary TS (sexual perversions,
      sexopathy). This distinction appears to the authors as unavoidable for ethico
      pathological and legal drive in view of the implications of T.S.--implications
      able to be analysed from standpoint.

PMID- 1344851
TI  - Psychopathological relationships in depressive illness.
AB  - The evolution of the clinical concepts regarding depressive syndromes underlines
      the need for correlating the epidemiological, clinical and etiopathogenic data
      for elaborating the classification, quantification and psychopathologic
      assessment systems. The psychological investigation, complementary to clinical
      examination and adapted to patient's subjective condition, requires an
      improvement of its methods in view of bringing more information necessary for
      stating the differential psychodiagnosis and for a proper psychotherapy. The
      analysis of motivations and the psychopathologic relationships in the depressive
      states render evident the factorial complexity and the need of a clinical,
      psychological, genetic, biochemical, experimental and therapeutic approach. Thus,
      a bio-medical and psychotherapeutic approach will improve the clinical research
      and psychopathologic assessment. The psychodiagnosis and psychotherapy, as
      elements of clinical care, make possible the clearing up of the therapeutic
      possibilities in the complex approach of personality, promoting the
      psychoprotective comprehension and the state of mental health.

PMID- 1344852
TI  - [The transient ischemic attack, between diagnosis and treatment].
AB  - The transient ischemic attack (TIA) in cerebral circulation in 161 patients is
      studied. The causes and favouring factors are analysed, arterial hypertension and
      dyslipidemias representing 70% of the factors that might be incriminated in the
      physiopathology of TIAs. The paraclinical and therapeutic results demonstrate
      that in over 30% of the cases the etiology could be explained by "the multiple
      defect theory", the importance of transcranial Doppler in the diagnosis and
      prognosis of TIA, especially in the young patients, being underlined.

PMID- 1344853
TI  - [Experimental data on epithelial factors modulating bronchial reactivity].
AB  - A tracheobronchial smooth muscle reactivity study on isolated guinea pig tracheal
      rings was done. The presence of two different factors active on smooth muscle, an
      inhibiting one, as well as an activating one was identified. Generated on
      different pathways, the epithelial derived relaxing factor is a cyclooxygenase
      dependent prostaglandin, while the activating epithelial factor seems to be a
      thromboxane derivate.

PMID- 1344854
TI  - [Two decades of epidemiologic surveillance of the evolution of viral hepatitis in
      Iasi County (1971-1990)].
AB  - The results of epidemiological observations on the evolution of viral hepatitis
      in the Iasi district in the interval 1971-1990 are presented. A mean morbidity of
      251.2 cases/100,000 inhabitants, this being in most years under the national
      mean, was found. In 75.9% of all cases the infections caused by hepatitis viruses
      affected the age-groups 1-14 years, indicating a high incidence of hepatitis A...
      Hepatitis B had a more increased incidence in the children aged 0-1 year, then it
      decreased but was present in all age groups. Although recorded all year round,
      increases in the incidence of viral hepatitis A were noticed during fall and
      winter seasons, prevailing in the children and teenagers collectivities.

PMID- 1344855
TI  - [Preliminary data on possibilities for the early detection of risk for primary
      liver carcinoma in chronic HBsAg carriers].
AB  - The investigations on the risk of hepatocarcinogenesis in the HBsAg chronic
      carriers have suggested that the early detection of primary liver carcinoma
      requires epidemiological and laboratory follow up of their state of health. The
      preliminary results of the comparative investigations of 103 HBsAg carriers
      detected among blood donors and 93 controls without HBsAg are presented.
      Epidemiological inquiries, clinical examinations and laboratory tests (HBsAg,
      serum alpha-fetoprotein, alkaline phosphatase, gamma-glutamyltranspeptidase,
      glutamic-pyruvic transaminase, proteinogram, siderophilin, immunoglobulins M, A,
      G) were carried out. Elevated levels of alpha-fetoprotein, alkaline phosphatase
      and gamma- glutamyltranspeptidase were recorded in carriers as compared to
      controls (38.8% and 86%, respectively). The elevation of the levels of liver
      damage markers was significantly correlated, in the HBsAg carriers, with the
      carrier state over 3 years and less with the age-group. In the case of two
      carriers with elevated levels of alpha-fetoprotein (> 600-> 1,000 ng/ml)
      ultrasonography confirmed the suspicion of primary liver carcinoma.

PMID- 1344856
TI  - [The etiology of acute viral hepatitis in Mures County].

PMID- 1344857
TI  - [Morbidity from various causes in rural children in the Republic of Moldova].
AB  - Child morbidity in the rural areas of the Republic of Moldavia was evaluated
      based on the data of attendances for medical care and complex medical
      examinations performed in 7,434 children aged between 0 and 14 years from five
      districts of the Republic. The age-group, sex and disease-groups distribution of
      morbidity are presented. These data were compared with the results obtained in
      other areas of the former Soviet Union. Measures for lowering the morbidity in
      the rural children of the Republic of Moldavia are suggested.

PMID- 1344858
TI  - The spread of X-linked shifting gene responsible for G-6-PD deficit in series of
      13,710 subjects from 4 districts of Moldavia.
AB  - Between 1985 and 1989, a sample of 13,710 subjects (5,825 males and 7,885
      females) from the Vrancea, Bacau, Neamt and Suceava districts were examined for
      the presence of this pathological gene, 32 male hemizygotes and 13 female
      heterozygotes and homozygotes being detected. The incidence of G-6-PD deficit in
      the hemizygotes was of 0.55%. The investigations carried out in the shifting gene
      carriers' families revealed the way deficit is transmitted to offsprings.
      Hemizygotes get it from their mother while the female homozygotes either from
      their mother or father. The frequency of G-6-PD deficit of 0.55% in a population
      sample of 13,710 subjects is within the limits established by Marcu and Schneer
      for our country (0.1-1.8%). By comparing the frequency of 0.55% in the Vrancea,
      Bacau, Neamt and Suceava districts which formerly had an increased incidence of
      malaria (Galati - 4.01% and Husi - 5.94%) its low value could be explained by the
      absence of malaria factor.

PMID- 1344859
TI  - [Glutathione and the redox index in different types of cellular oxidative stress.
      I. Acrylonitrile (ACN) poisoning].
AB  - The professional poisoning with acrylonitrile of some subjects induced a
      significant decrease of reduced glutathione (81.30%), redox ratio reduced
      glutathione/oxidized glutathione (90.74%) and "Benzi-redox index" (55.84%) but an
      increase of oxidized glutathione level (112.6%) as compared to normal controls
      (100%). This proves the occurrence, in time, of the cellular oxidative stress
      and/or were obtained.

PMID- 1344861
TI  - [Environmental pollution studies of fluorine coming from industry].
AB  - Fluorine in optimal concentration prevents dental caries, while an excess or
      deficiency in it may lead to pathologic alterations which make fluorine be one of
      the environmental pollutants the concentration of which is limited by health
      standards. This investigation, carried out in the area of an aluminium plant,
      showed the presence in excess of fluorine and fluorine-containing dusts in the
      atmospheric air, determining an increased fluorine content in the ground and
      vegetal cultures of the respective area. Negative effects of these noxae upon
      vegetation and animals were noticed.

PMID- 1344860
TI  - [A population study on the possible involvement of trace minerals in water in
      cardiovascular diseases].
AB  - Starting from the hypothesis of a possible protection exerted by oligominerals in
      cardiovascular diseases, 660 water sources were analysed as to their content in
      mineral matter. It resulted that the population drinks a very hard water with a
      low content in zinc, manganese, copper and chromium oligominerals. By correlating
      these characteristics with the mortality rate by cardiovascular diseases, low in
      the territory under study, it became evident that no association between these
      factors can be made, the relative protection being probably due to other factors.

PMID- 1344862
TI  - [The synthesis of new pyrrolidone derivatives with psychotropic action].
AB  - The synthesis of ten new heterocyclic compounds obtained by the addition of
      pyrrolidone to heterocumulenes and its condensation or of its sodic derivative
      with acid chlorides is presented. The synthetized pyrolidonic derivatives were
      subjected to a preliminary study for determining their possible psychotropic
      action. The pharmacological screening evidenced a significant hypothermisante and
      neurodynamic-nootropic action of some synthetized compounds.

PMID- 1344863
TI  - [Analytical study of theophylline-rutozide (TR-1722)].
AB  - A compound obtained by the semisynthesis of theophylline and rutozid was analysed
      elementary and physicochemically. The performed analyses showed that it was 7
      rutozidil-is-propanolen-theophylline.

PMID- 1344864
TI  - [Antimicrobial activities of organic zinc compounds].
AB  - Taking into account the competitive action of zinc towards other ion essential
      for pathogenic germs metabolism, the complex erythromycin-zinc, zinc salts of
      sulfamethoxydiazine, sulfanilamide, sulfacetimide, sulfathiazole as well as the
      Mannich basis of sulfamethoxydiazine were synthetized. The antimicrobial action
      towards gram-positive, gram-negative pathogens and fungi was tested by the
      classic diffusiometric method. An increased antimicrobial action for the Mannich
      basis of sulfamethoxydiazine and for the zinc salt of sulfamethoxydiazine, alone
      or in association with metronidazole--chemotherapeutic agent used in the
      infections with anaerobic organisms was found. A significant antimicrobial action
      was also found for the complex erythromycin-zinc and zinc salts of sulfacetimide
      and sulfathiazole.

PMID- 1344865
TI  - [Methodology for quality control of an ointment with antivaricose properties].
AB  - A personal formulation of an ointment with antivaricose properties is presented.
      A methodology for the physicochemical and rheologic control, including all
      parameters required by the standards for ointments quality control, was designed.
      The analyses showed that the ointment is stable in time, has a thixotropic
      consistency and behaviour and does not require special preservation conditions.

PMID- 1344867
TI  - On hypotensive action of some imidazoline derivatives of sulphonamidated
      aryloxyalkylcarboxylic acids.
AB  - New imidazolines derived from sulphonamidated aryloxyalkylcarboxylic acids have
      been tested for their antihypertensive action and toxicity. The obtained results
      attest a remarkable biological action, low toxicity and a good absorption in oral
      administration.

PMID- 1344866
TI  - [New derivatives of pyrazolo- and tetrazolobenzoquinolines with antimicrobial
      action].
AB  - The conditions for obtaining and the properties of some new diazabicyclic
      compounds is the new step in our investigation on the benzocynoline derivatives.
      The structure of the new compounds was confirmed by elementary (C, H, N) and
      spectral analyses. The antimicrobial tests evidenced that part of the newly
      synthetized compounds have a good antifungal action.

PMID- 1344868
TI  - [Mitral valve prolapse. I. The nosological picture, anatomical spectrum and
      prevalence].

PMID- 1344869
TI  - [Clinical manifestations of Lyme disease].

PMID- 1344870
TI  - [Deviance as a potential source and action in aggressive behaviors].

PMID- 1344871
TI  - [Oxygen biochemistry. I. Reactive species of reduced oxygen and endogenous
      sources].

PMID- 1344872
TI  - [Hypothalamic and hypophyseal peptides at the placental level].

PMID- 1344873
TI  - [Situational psychiatric understanding of the genetic contribution (II)].

PMID- 1344874
TI  - [Update in vaccinal prevention].

PMID- 1344875
TI  - [Nutrition and cancer].

PMID- 1344876
TI  - [AIDS. Professional risk in dental practice?].

PMID- 1344877
TI  - [Painters, drawers and engravers with medical themes (V)].

PMID- 1344878
TI  - [Theme of the labyrinth in the cult of Asklepios].

PMID- 1344879
TI  - Experience with vaginal reconstruction utilizing the modified Singapore flap.
AB  - Many types of vaginal reconstruction have been described, and we have employed
      several with varying degrees of success. All we have used seem to have drawbacks.
      In April 1989 Wee and Joseph from Singapore described a technique using
      neurovascular pudendal-thigh flaps as islands. Initially we used the procedure as
      described. Later we modified the approach by releasing the labia majora, allowing
      them to retract somewhat anteriorly, and rotating the flap into position. This
      procedure has been used in eight patients, in some instances under the most
      adverse circumstances in patients who have undergone multiple procedures and
      heavy irradiation (including intraoperative radiation) besides experiencing
      postoperative leakage of urine. Though we have had dehiscence and problems with
      infection and drainage in some of our patients, no flap has failed, contour is
      exceptionally good, and potential for function is satisfactory. The procedure
      requires less time and produces better results than any other technique employed
      by us in the more than 30 vaginal reconstructions we have carried out. The
      technique will be illustrated and clinical cases will be presented.

PMID- 1344880
TI  - Luteal phase deficiency: effect of treatment on pregnancy rates.
AB  - Luteal phase deficiency is thought to be a cause of female infertility.
      Nevertheless, little agreement exists concerning either its diagnosis or its
      treatment. To address the latter question, we reviewed the English literature and
      examined the effect of treatment on pregnancy rates. One randomized controlled
      trial found a statistically insignificant benefit of treatment with progesterone
      suppositories or oral dehydroprogesterone versus no treatment (relative risk 1.9;
      95% confidence interval 0.4 to 8.1). Three other comparative studies also showed
      no statistically significant benefit. Case-series reports (before-after studies)
      claiming benefit failed to account for the effect of regression to the mean. The
      benefit of treatment for luteal phase deficiency has not been established.
      Uniform case definitions and randomized controlled trials of adequate power are
      needed to resolve this problem.

PMID- 1344881
TI  - beta-Lactamases and susceptibility to beta-lactam antibiotics in Escherichia
      coli.

PMID- 1344882
TI  - Substrate synergism and the steady-state kinetic reaction mechanism for EPSP
      synthase from Escherichia coli.
AB  - Previous studies of Escherichia coli 5-enolpyruvoylshikimate-3-phosphate synthase
      (EPSPS, EC 2.5.1.19) have suggested that the kinetic reaction mechanism for this
      enzyme in the forward direction is equilibrium ordered with shikimate 3-phosphate
      (S3P) binding first followed by phosphoenolpyruvate (PEP). Recent results from
      this laboratory, however, measuring direct binding of PEP and PEP analogues to
      free EPSPS suggest more random character to the enzyme. Steady-state kinetic and
      spectroscopic studies presented here indicate that E. coli EPSPS does indeed
      follow a random kinetic mechanism. Initial velocity studies with S3P and PEP show
      competitive substrate inhibition by PEP added to a normal intersecting pattern.
      Substrate inhibition is proposed to occur by competitive binding of PEP at the
      S3P site [Ki(PEP) = 6-8 mM]. To test for a productive EPSPS.PEP binary complex,
      the reaction order of EPSPS was evaluated with shikimic acid and PEP as
      substrates. The mechanism for this reaction is equilibrium ordered with PEP
      binding first giving a Kia value for PEP in agreement with the independently
      measured Kd of 0.39 mM (shikimate Km = 25 mM). Results from this study also show
      that the 3-phosphate moiety of S3P offers 8.7 kcal/mol in binding energy versus a
      hydroxyl in this position. Over 60% of this binding energy is expressed in
      binding of substrate to enzyme rather than toward increasing kcat. Glyphosate
      inhibition of shikimate turnover was poor with approximately 8 x 10(4) loss in
      binding capacity compared to the normal reaction, consistent with the
      independently measured Kd of 12 mM for the EPSPS.glyphosate binary complex. The
      EPSPS.glyphosate complex induces shikimate binding, however, by a factor of 7
      greater than EPSPS.PEP. Carboxyallenyl phosphate and (Z)-3-fluoro-PEP were found
      to be strong inhibitors of the enzyme that have surprising affinity for the S3P
      binding domain in addition to the PEP site as measured both kinetically and by
      direct observation with 31P NMR. The collective data indicate that the true
      kinetic mechanism for EPSPS in the forward direction is random with synergistic
      binding occurring between substrates and inhibitors. The synergism explains how
      the mechanism can be random with S3P and PEP, but yet equilibrium ordered with
      PEP binding first for shikimate turnover. Synergism also accounts for how
      glyphosate can be a strong inhibitor of the normal reaction, but poor versus
      shikimate turnover.

PMID- 1344883
TI  - Cloning and sequencing of cDNAs encoding two S proteins of a self-compatible
      cultivar of Petunia hybrida.
AB  - A defective S-allele, S(o), and a functional S-allele, Sx, have previously been
      found to be retained in an F1 hybrid of a self-compatible commercial cultivar of
      Petunia hybrida. Pistil proteins associated with these two alleles have also been
      identified. Their amino-terminal sequences have been found to share a high degree
      of similarity with those of S-proteins characterized from self-incompatible
      solanaceous species. Here we report the isolation and sequencing of cDNAs
      encoding S(o)- and Sx-proteins. Their deduced amino acid sequences contain all
      the consensus primary structural features of S-proteins from self-incompatible
      solanaceous species. Both proteins also have ribonuclease activity. The
      implications of these findings are discussed in relation to the presumed function
      of the S-protein in the self-incompatibility interaction.

PMID- 1344885
TI  - Bean homologs of the mammalian glucose-regulated proteins: induction by
      tunicamycin and interaction with newly synthesized seed storage proteins in the
      endoplasmic reticulum.
AB  - Treatment of developing bean cotyledons with the inhibitor of N-glycosylation
      tunicamycin enhanced the synthesis of at least two polypeptides with molecular
      mass 78 kDa and 97 kDa. Pulse-chase experiments and subcellular fractionation
      indicated that these are endoplasmic reticulum (ER) residents. The 78 kDa protein
      is a major component of the ER protein fraction and, by N-terminal sequencing,
      was identified as a bean homolog of the mammalian 78 kDa glucose-regulated
      protein (GRP78). This is a molecular chaperone that is probably involved in the
      folding and oligomerization of several animal and yeast proteins in the ER. When
      newly synthesized storage glycoproteins phaseolin, phytohemagglutinin or alpha
      amylase inhibitor were immunoprecipitated from an ER preparation of tunicamycin
      treated tissue, the GRP78 homolog was always co-precipitated. Bound GRP78 homolog
      could be released by ATP treatment. These results suggest that, at least when
      glycosylation is inhibited, this protein plays a role in the early stages of the
      synthesis of vacuolar storage proteins.

PMID- 1344884
TI  - 2,3,4,6-Tetra-O-benzyl-beta-D-galactopyranosyl phenyl sulfoxide as a glycosyl
      donor. Synthesis of some oligosaccharides containing an alpha-D-galactopyranosyl
      group.

PMID- 1344886
TI  - The methylation patterns of chromosomal integration regions influence gene
      activity of transferred DNA in Petunia hybrida.
AB  - The regions of integration of a transferred DNA-fragment from three transgenic
      Petunia hybrida plants were analysed for their influence on the expression of the
      foreign DNA. Each of the three transformants, lines 16, 17 and 24, contained a
      fragment of a plasmid on which two genes were located, an npt-II gene which
      renders the plants resistant to kanamycin and the A1 gene from Zea mays, a
      visible marker gene that leads to the production of a brick red anthocyanin
      pigment in the flowers. Inactivation of both genes in line 16 is associated with
      integration into a region of highly repetitive DNA, while the integration sites
      of the other two lines were essentially unique. The integration regions of lines
      17 and 24, both of which show expression of the foreign genes at
      characteristically different intensities, showed a distinct methylation pattern
      that was stably conserved for these regions in both transgenic and wild-type
      plants. The characteristic methylation pattern of the two integration regions was
      also imposed on the border region of the integrated fragments and might thus be
      responsible for the differences in the intensity of gene expression observed
      among the two lines.

PMID- 1344887
TI  - Promoter elements involved in environmental and developmental control of potato
      proteinase inhibitor II expression.
AB  - The proteinase inhibitor II (pin2) gene family exhibits two different modes of
      expression. It is, on the one hand, constitutively expressed in flowers of potato
      and tomato plants. and in potato tubers. On the other hand, its expression is
      induced in the plant foliage by mechanical wounding. To define cis-regulatory
      elements involved in pin2 promoter activity, deletion analysis of a potato pin2
      promoter has been performed in stably and transiently transformed potato and
      tobacco plants. Two different elements, a quantitative enhancer and a regulatory
      element, are required for promoter activity. While functional promoter elements
      required for pin2 activity in tubers and wounded leaves could not be separated,
      its expression in flowers is mediated by different cis-acting sequences.
      Induction of pin2 expression in leaves by treatment with the plant growth
      regulators abscisic acid and jasmonic acid, and the general metabolite sucrose,
      depends on the presence of the regulatory element involved in expression in
      tubers and wounded leaves. Thus, pin2 expression in tubers and wounded leaves
      apparently results from the action of similar hormonal signals on closely linked
      promoter elements, while a different signal pathway leads to its constitutive
      expression in flowers.

PMID- 1344888
TI  - Metabolic regulation of rice alpha-amylase and sucrose synthase genes in planta.
AB  - Isolated rice embryos were used to investigate the regulatory effects of
      endosperm extracts and pure sugars on the expression of alpha-amylase gene RAmy3D
      and a sucrose synthase gene homologous to the maize isozyme Ss2. The high-level
      expression of RAmy3D in the scutella of isolated embryos could be inhibited by a
      variety of sugars as well as endosperm extracts from germinated rice grains.
      Glucose, at a concentration of 250 mM, was most effective in repressing RAmy3D
      mRNA accumulation. Furthermore, this repression was reversible. Interestingly,
      RAmy3D repression was always accompanied by the induction of sucrose synthase
      gene expression. These results support a model in which the expression of alpha
      amylase and sucrose synthase genes in the rice scutellum are counter-regulated by
      the influx of sugars from the endosperm.

PMID- 1344889
TI  - The TACPyAT repeats in the chalcone synthase promoter of Petunia hybrida act as a
      dominant negative cis-acting module in the control of organ-specific expression.
AB  - Analysis of the expression of the GUS reporter gene driven by various regions of
      the Petunia hybrida chalcone synthase (chsA) promoter revealed that the
      developmental and organ-specific expression of the chsA gene is conferred by a
      TATA proximal module located between -67 and -53, previously designated as the
      TACPyAT repeats. Histochemical analysis of GUS reporter gene expression revealed
      that the organ-specific 67 bp promoter fragment directs the same cell-type
      specificity as a 530 bp promoter, whereas additional enhancer sequences are
      present within the more TATA distal region. Moreover, the region between -800 and
      -530 is also involved in extending the cell-type specificity to the trichomes of
      flower organs and of young seedlings. The mechanism by which the TACPyAT repeats
      modulate expression during plant development was studied by analysing the
      expression of the GUS gene driven by chimeric promoters consisting of the CaMV
      35S enhancer (domain B, -750 to -90) fused to various chsA 5' upstream sequences.
      Detailed enzymatic and histochemical analysis revealed that in the presence of
      the TACPyAT module the CaMV 35S region only enhances GUS activity in those organs
      in which the chsA promoter is normally active. Furthermore, this analysis shows
      that enhancement in the presence of the CaMV 35S domain B is accomplished by
      increasing the number of cell types expressing the GUS gene within the organ,
      rather than enhancement of the chsA cell-type-specific expression within these
      organs. Deletion of the TACPyAT sequences in the chimeric promoter construct
      completely restores the well-documented CaMV 35S domain B cell-type specificity,
      showing that the TACPyAT module acts as a dominant negative cis-acting element
      which controls both organ and developmental regulation of the chsA promoter
      activity.

PMID- 1344890
TI  - Potato virus X as a vector for gene expression in plants.
AB  - The suitability of potato virus X (PVX) as a gene vector in plants was tested by
      analysis of two viral constructs. In the first, the GUS gene of Escherichia coli
      was substituted for the viral coat protein gene. In the second, GUS was added
      into the viral genome coupled to a duplicated copy of the viral promoter for the
      coat protein mRNA. The viral construct with the substituted coat protein gene
      accumulated poorly in inoculated protoplasts and failed to spread from the site
      of infection in plants. These results suggest a role for the viral coat protein
      in key stages of the viral infection cycle and show that gene replacement
      constructs are not suitable for the production of PVX-based gene vector. The
      construct with GUS coupled to the duplicated promoter for coat protein mRNA also
      accumulated less well in protoplasts than the unmodified PVX, but did infect
      systemically and directed high level synthesis of GUS in inoculated and
      systemically infected tissue. Although there was some genome instability in the
      PVX construct, much of the viral RNA in the systemically infected tissue had
      retained the foreign gene insertion, especially in infected Nicotiana clevelandii
      plants. These data point to a general utility of PVX as a vector for unregulated
      gene expression in plants.

PMID- 1344891
TI  - Expression of E. coli inorganic pyrophosphatase in transgenic plants alters
      photoassimilate partitioning.
AB  - Transgenic plants were constructed expressing a novel cytosolic inorganic
      pyrophosphatase in order to reduce the cytosolic pyrophosphate content. To this
      end the Escherichia coli gene ppa encoding inorganic pyrophosphatase was cloned
      between the 35S CaMV promoter and the poly(A) site of the octopine synthase gene
      and transferred into tobacco and potato plants by Agrobacterium-mediated gene
      transfer. Regenerated plants were tested for the expression of the ppa gene by
      Northern blots and activity gels. Plants expressing active inorganic
      pyrophosphatase showed a dramatic change in photoassimilate partitioning. In both
      transgenic tobacco and potato plants the ratio between soluble sugars and starch
      was increased by about 3-4-fold in source leaves as compared with the wild-type.
      However, whereas source leaves of transgenic tobacco plants accumulated much
      higher levels of glucose (up to 68-fold), fructose (up to 24-fold), sucrose (up
      to 12-fold) and starch (up to 8-fold) this was not observed in potato plants
      where the change in assimilate partitioning in source leaves was due to an
      increase of about 2-fold in sucrose and a reduction in starch content. Expression
      of the cytosolic inorganic pyrophosphatase in tobacco results in stunted growth
      of vegetatively growing plants due to a reduced internode distance. Upon
      flowering the transgenic plants increase their growth rate, reaching almost the
      same height as control plants at the end of the growth period. Old source leaves
      accumulate up to 100-fold more soluble sugars than control leaves. This increase
      in soluble sugars is accompanied by a reduction in chlorophyll content (up to
      85%). Transgenic potato plants showed a less dramatic change in their growth
      behaviour. Plants were slightly reduced in size, with stems more highly branched.
      Tuber number increased 2-3-fold, but tuber weight was lower resulting in no net
      increase in fresh weight.

PMID- 1344892
TI  - Construction and expression of nonsense suppressor tRNAs which function in plant
      cells.
AB  - An Arabidopsis thaliana L. DNA containing the tRNA(TrpUGG) gene was isolated and
      altered to encode the amber suppressor tRNA(TrpUAG) or the ochre suppressor
      tRNA(TrpUAA). These DNAs were electroporated into carrot protoplasts and tRNA
      expression was demonstrated by the translational suppression of amber and ochre
      nonsense mutations in the chloramphenicol acetyltransferase (CAT) reporter gene.
      DNAs encoding tRNA(TrpUAG) and tRNA(TrpUAA) nonsense suppressor tRNAs caused
      suppression of their cognate nonsense codons in CAT mRNAs, with the tRNA(TrpUAG)
      gene exhibiting the greater suppression under optimal conditions for expression
      of CAT. The development of these translational suppressors which function in
      plant cells facilitates the study of plant tRNA gene expression and will make
      possible the manipulation of plant protein structure and function.

PMID- 1344893
TI  - Molecular comparison of monocot and dicot U1 and U2 snRNAs.
AB  - To elucidate differences between the pre-mRNA splicing components in monocots and
      dicots, we have cloned and characterized several U1 and U2 snRNA sequence
      variants expressed in wheat seedling nuclei. Primer extension sequencing on wheat
      and pea snRNA populations has demonstrated that two 5'-terminal nucleotides found
      in most other U1 snRNAs are missing/modified in many plant U1 snRNAs. Comparison
      of the wheat U1 and U2 snRNA variants with their counterparts expressed in pea
      nuclei has defined regions of structural divergence between monocot and dicot U1
      and U2 snRNAs. The U1 and U2 snRNA sequences involved in RNA:RNA interaction with
      pre-mRNAs are absolutely conserved. Significant differences occur between wheat
      and pea U1 snRNAs in stem I and II structures implicated in the binding of U1
      specific proteins suggesting that the monocot and dicot U1-specific snRNP
      proteins differ in their binding specificities. Stem III structures, which are
      required in mammalian systems for splicing complex formation but not for U1
      specific protein binding, differ more extensively than stems I, II, or IV. In U2
      snRNAs, the sequence differences between these two species are primarily
      localized in stem III and in stem IV which has been implicated in snRNP protein
      binding. These differences suggest that monocot and dicot U1 and U2 snRNPs
      represent distinct entities that may have monocot- and dicot-specific snRNP
      protein variants associated with each snRNA.

PMID- 1344894
TI  - Immunomodulatory effects of fusarochromanones TDP-1 and TDP-2.
AB  - An in vitro peripheral lymphocyte blastogenesis system was used to investigate
      the biological activities of the fungal toxin fusarochromanone (TDP-1) and its
      monoacetyl derivative TDP-2. Briefly, cultures of human or bovine peripheral
      lymphocytes were exposed to TDP-1 or TDP-2 and a mitogen (PHA, Con A or PWM).
      After a standard incubation time, cell proliferation was quantified using the MTT
      bioassay. Human and bovine lymphocyte proliferation was inhibited by high
      concentrations of TDP-1; however, bovine lymphocyte proliferation was
      significantly increased at low concentrations of TDP-1. TDP-2 has similar but
      less pronounced effects on lymphocyte proliferation.

PMID- 1344896
TI  - Nature's pesticides.

PMID- 1344895
TI  - Light and electron microscopic studies of the murine heart after repeated
      administrations of ciguatoxin or ciguatoxin-4c.
AB  - After repeated ip and oral administrations of ciguatoxin (CTX) and ciguatoxin-4c
      (CTX-4c), one of the derivatives of CTX, to male ICR mice at a dose of 0.1
      microgram/kg for 15 days, resulted in marked swelling of cardiac cells and
      endothelial lining cells of blood capillaries in the heart was observed. Single
      doses caused no discernible pathological changes. Damage to the capillaries was
      followed by prominent effusion of serum and erythrocytes into the interstitial
      spaces of the myocardium occurred. Swelling of the endothelial lining cells of
      capillaries caused narrowing of the lumen and accumulation of blood platelets in
      capillaries, which resulted in multiple single cell necroses of cardiac muscle
      cells. Within 1 month after the treatments of these phycotoxins, myocytes and
      capillaries appeared to be normal. Effusion in the interstitial spaces resulted
      in formation of bundles of dense collagen, which persisted for 14 months. Diffuse
      interstitial fibrosis was prominent in septum and ventricles, accompanied by
      bilateral ventricular hypertrophy. A single dose of 0.7 micrograms/kg ip resulted
      in severe acute heart injuries, followed by diffuse myocardial fibrosis.

PMID- 1344897
TI  - Genotoxicity of fungi evaluated by SOS microplate assay.
AB  - By an introduction of sodium dodecylsulfate for cell lysis and immunomicroplate
      for mass assay, the modified SOS microplate assay method was established and
      applied for the evaluation of genotoxicity of mycotoxins and fungal cultures.
      Among 20 mycotoxins, the carcinogenic dihydrobisfuranoids such as aflatoxin B1,
      sterigmatocystin, and versicolorin A were positive in the presence of the
      activation system. While, the carcinogenic anthraquinones and lactones such as
      luteoskyrin, rugulosin, ochratoxin A, patulin, and citrinin were negative. The
      survey on genotoxic fungi revealed that, among 15 fungal isolates Aspergillus
      versicolor, Emericella acristata, and others were positive. Additional survey on
      265 fungal isolates have revealed that various Aspergillus genera such as A.
      flavus, A. parasiticus, A. ustus, A. nidulans, and others were positive for SOS
      induction, along with several isolates of Fusarium moniliforme. The chemical
      analysis revealed that the dihydrobisfuranoids such as aflatoxin B1, and
      sterigmatocystin were the major genotoxic metabolites of several Aspergillus
      species. The SOS microplate assay system is a simple and rapid procedure for the
      mass screening of genotoxic fungi, particularly of the dihydrobisfuranoids
      producing strains.

PMID- 1344898
TI  - Pyrrolizidine alkaloids from Melampyrum pratense.

PMID- 1344899
TI  - Trichothecene synergism, additivity, and antagonism: the significance of the
      maximally quiescent ratio.
AB  - The interactive effect of the combinations of trichothecene mycotoxins often
      found in fungus infected plants, contaminated grain, and other biological systems
      is poorly understood. Growth inhibition of the yeast Kluyveromyces marxianus was
      used to measure the effects of HT-2 toxin, roridin A, and T-2 toxin as individual
      toxins or as binary mixtures. A value, the combination index, was derived which
      indicates the interactive effects of a binary mixture of toxins. The interaction
      is affected by the ratio of the individual toxins, and the percent inhibition of
      yeast growth. Generally the interaction of T-2 toxin and roridin A or T-2 toxin
      and HT-2 toxin changes from antagonistic when they cause a low percent inhibition
      of yeast growth to synergistic when they cause a high percent inhibition of yeast
      growth. Additionally, any two trichothecenes have a unique ratio, which we name
      the maximally quiescent ratio (or MQR), where there is the least change in the
      type and intensity of their interaction. The maximally quiescent ratio in this
      case has helped to define the nature of toxin interactions and could be used to
      provide insights into hormone, immune system, developmental, enzyme, and gene
      regulation, combined drug therapy, and the action of mixtures of natural or
      synthetic toxins, carcinogens, pesticides, and environmental pollutants.

PMID- 1344900
TI  - Bullatencin, 4-deoxyasimicin, and the uvariamicins: additional bioactive
      Annonaceous acetogenins from Annona bullata Rich. (Annonaceae).
AB  - Additional bioactive Annonaceous acetogenins have been isolated from the EtOH
      extract of the bark of Annona bullata Rich. by bioactivity-directed fractionation
      using lethality to brine shrimp. These acetogenins include bullatencin, a new
      single tetrahydrofuran acetogenin having a double bond in the hydrocarbon chain;
      4-deoxyasimicin, a new adjacent bis-tetrahydrofuran acetogenin; and the
      uvariamicins, an isomeric mixture of four single tetrahydrofuran acetogenins
      showed selective cytotoxicities for certain human solid tumor cell lines
      comparable to or better than adriamycin.

PMID- 1344901
TI  - Release of heptapeptide toxin (microcystin) during the decomposition process of
      Microcystis aeruginosa.
AB  - The decomposition process of toxic blue-green alga (cyanobacteria), Microcystis
      aeruginosa, under dark and aerobic condition was investigated in relation to the
      change of the amounts of heptapeptide toxins (microcystins YR and LR) by two
      experiments: one with Microcystis cells and the other with two purified
      microcystins. In the experiment with Microcystis cells, an increase of
      heterotrophic bacteria observed from the beginning of the experiment, was
      followed by decomposition of the algal cells and the subsequent release of
      microcystins into the filtrate fraction. The amounts of the toxins initially
      present in the cells were quantitatively detected in the filtrate fraction on the
      35th day. The decomposition of microcystin YR began on the 42nd day. The
      decomposition rate of the two toxins was different. The decomposition rate of
      purified microcystins YR and LR, compared in distilled water and culture medium,
      respectively, indicated clearly that microcystin YR was more labile to
      decomposition than microcystin LR in the culture medium. At the end of the
      experiment (45th day) microcystin YR decreased to 58.6%, while 86.2% of
      microcystin LR remained.

PMID- 1344902
TI  - The amino acid sequence of toxin IV from the Androctonus australis scorpion:
      differing effects of natural mutations in scorpion alpha-toxins on their
      antigenic and toxic properties.
AB  - The complete amino acid sequence (64 residues) of the AaH IV toxin from the
      scorpion Androctonus australis Hector was determined by automated Edman
      degradation and was compared with the sequences of other Androctonus toxins. AaH
      IV was also tested by radioimmunoassay for binding to antisera raised against
      other toxins of the same species. The results indicated that AaH IV shares some
      of the antigenic properties of AaH I and AaH III toxins, but does not cross-react
      with anti-AaH II antibodies. The structural basis for the observed antigenic
      relationships can be found in the high degree of homology displayed by AaH IV
      with regard to AaH I and III, the changes in amino acid residues equally
      affecting regions included or excluded from the main predicted antigenic sites of
      AaH IV. The lower biological potency of AaH IV is presumably the result of some
      of the sequence differences. In particular, substitution affecting the charge and
      bulkiness of residue 61 could account for the poor receptor binding and
      consequential weak toxic properties of this molecule.

PMID- 1344903
TI  - Aflatoxins isolated by immunoaffinity chromatography from foods consumed in The
      Gambia, West Africa.
AB  - An aflatoxin-specific, monoclonal antibody-based immunoaffinity chromatography
      method has been developed for the rapid isolation of aflatoxins from human foods.
      Aflatoxins were isolated by immunoaffinity chromatography from a variety of
      cooked foods, including maize, rice, millets, groundnut sauces, and leaf sauces,
      collected in The Gambia, West Africa. The aflatoxins were measured by direct
      fluorescence or high-pressure liquid chromatography. The highest levels were
      found for groundnut sauces, mean 162 ppb (range 18 to 943 ppb) for 18 positive
      samples, but aflatoxins were found in other foods; e.g., maize, mean 9.7 ppb
      (range 2 to 35 ppb) for nine positive samples. The food analysis results were
      used with records of the amounts of cooked food to estimate a mean daily intake
      for an individual of the order of 3.5 micrograms of aflatoxins per day. This
      approach for exposure assessment is considered in relation to other biomarkers of
      aflatoxin exposure using biological fluids.

PMID- 1344904
TI  - The hemolytic activity of deoxynivalenol and T-2 toxin.
AB  - The hemolytic effects of deoxynivalenol (DON) and T-2 toxin (T-2) individually on
      rat erythrocytes were studied at different concentrations. Sodium azide was used
      as an enzyme inhibitor to prevent T-2 toxin metabolism. The concentration of T-2
      was controlled by GC-MS and no decrease of the toxin was found during the time of
      the experiment. In spite of the much higher toxicity of T-2 toxin to eucaryotic
      cells, DON and T-2 showed similar lytic activity toward erythrocytes at high and
      low concentrations. Neither of these toxins at a concentration of 130
      micrograms/ml, produced significant hemolysis even after 11 hr incubation. This
      finding suggests that there is a threshold level for both T-2 and DON, below
      which the lytic reaction does not occur. An additional hemolysis test was
      conducted in the presence of mannitol, glutathione, ascorbic acid, alfa
      tocopherol, and histidine. The assay demonstrated that all the compounds
      inhibited to some extent the hemolytic reaction of the toxins. It is suggested
      that DON and T-2 exert their toxicity on procaryotic cells in three different
      ways: by penetrating the phospholipid bilayer and acting at the subcellular
      level, by interacting with the cellular membranes, and by free radical mediated
      phospholipid peroxidation. Most probably, more than one mechanism operates at the
      same time.

PMID- 1344905
TI  - Short term effects of animal venoms on the mitotic index of the duodenal mucosa
      of albino rats.
AB  - Short term administration of the venoms of the snakes Naja haje, Naja
      nigricollis, and Cerastes vipera and of the scorpion Leiurus quinquestriatus on
      the mitotic index of the duodenal mucosal cells of the white rat, Rattus rattus,
      has been studied. All the venoms increased the number of dividing cells of the
      duodenal mucosa significantly. Naja haje crude venom was fractionated into three
      fractions. Fraction I had no effect on the mitotic index whereas fractions II and
      III increased it significantly. Treatment of rats with Naja haje venom fractions
      II and III after blocking the histamine or the serotonin receptors did not affect
      the stimulatory action of the two venom fractions on the mitotic index, which it
      increased significantly. It was suggested that the venoms of Naja haje, Naja
      nigricollis, Cerastes vipera, and Leiurus quinquestriatus and Naja haje venom
      fractions possessed a mitogenic activity. Fraction II of Naja haje venom acted
      through both the muscarinic and adrenergic receptors while fraction III acted on
      the adrenergic ones.

PMID- 1344906
TI  - The beta-type toxin Ts II from the scorpion Tityus serrulatus: amino acid
      sequence determination and assessment of biological and antigenic properties.
AB  - The toxin Ts II from the venom of the Brazilian scorpion Tityus serrulatus was
      purified in two successive chromatographic steps. The amino acid sequence was
      then determined by automated Edman degradation of the reduced and S
      carboxymethylated protein and of proteolytic peptides derived from it. This
      sequence appears to differ from that of previously characterized toxins found in
      this venom. However, it is identical to the recently published sequence of
      protein III-8 from the same venom [Possani et al., J Biol Chem 266:3178-3185,
      1991], except that the C-terminus was found to be amidated. Homologies were found
      between the sequence of Ts II and that of other toxins from Tityus; in
      particular, the amino acid sequence of Ts II displays 72% sequence identity with
      Ts VII (also called Titx gamma). Consistent with this structural similarity, some
      biological properties of Ts II were found to be similar to those of Ts VII: Ts II
      has an intracerebroventricular LD50 of 6 ng, as compared to 0.6 ng for Ts VII; in
      a receptor binding assay Ts II, like Ts VII, was found to behave as a beta-type
      toxin and to inhibit the binding of the reference labelled toxin with a K0.5 of 5
      x 10(-9) M, as compared to 7 x 10(-11) M for Ts VII. Nevertheless, Ts II is
      unable to bind to anti-Ts VII antibodies in radioimmunoassay experiments,
      indicating the non-conservation between the two toxins of at least some
      antigenically important residues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1344907
TI  - The effects of ciguatoxin on the nerves of the teleost fish, Sillago ciliata.
AB  - The absolute refractory period, relative refractory period, and the duration and
      magnitude of the supernormal period were measured after incubation of fish nerves
      with ciguatoxin and other channel modifying compounds, tetrodotoxin, veratridine,
      verapamil, and lignocaine. In vitro electrophysiological studies were carried out
      on the lateral line nerve of the whiting, Sillago ciliata Cuvier.
      Electrophysiological changes in fish nerves after exposure to ciguatoxin (0.3
      MU.ml-1) and veratridine (1 x 10(-5) M) are similar to changes that occur in
      mammalian nerves and include an increase in the absolute refractory period, the
      relative refractory period, and the magnitude and duration of supernormality. The
      effects of ciguatoxin (0.3 MU.ml-1) in fish nerves were antagonised by
      tetrodotoxin (5 x 10(-10) M), verapamil (5 x 10(-7) M), and lignocaine (1 x 10(
      5) g/ml-1). The nerves of Sillago ciliata used in this study responded to
      ciguatoxin and its antagonists in a similar manner to mammalian nerves,
      suggesting that these teleost nerves have no specific electrophysiological
      mechanism to cope with this toxin.

PMID- 1344908
TI  - Novel study on the elicitation of hypersensitive response by polyunsaturated
      fatty acids in potato tuber.
AB  - A GC-MS procedure was carried out for the simultaneous and unequivocal
      quantitation of both potato phytoalexin (rishitin and lubimin) accumulation and
      the rate of disappearance of polyunsaturated fatty acids (PUFA) and some of their
      esters tested as possible elicitors. Potato 5-lipoxygenase and lipolytic acyl
      hydrolase play a key role in hypersensitive response (HR) induction. As expected,
      arachidonic acid, its hydrolysable esters, and eicosapentaenoic acid elicited
      much higher HR than the other PUFA tested, although the latter were equally
      affected by potato 5-lipoxygenase. Hydroxyl radicals appear to be actively
      involved in the browning process. The polyaminoacid poly-L-lysine did not show
      any eliciting activity.

PMID- 1344909
TI  - Risk assessment and natural toxins.

PMID- 1344910
TI  - Poisoning by Coprinus atramentarius.
AB  - The ink cap--Coprinus atramentarius (Bulliard ex Fries) Fries--is responsible for
      poisoning when ingested with alcohol. The investigation of the "Coprinus
      syndrome," although a minor poisoning incident, stimulated numerous research
      programs because the results were expected to yield a novel drug useful during
      the treatment of alcoholism. This work led to the identification of the active
      principle--coprine--and to an explanation of its mode of action; nevertheless,
      detailed toxicology investigations have shown that the mutagenic and gonadotoxic
      properties of this compound made it unsuitable for therapeutic use. Our current
      knowledge of the poisoning, the chemistry of the toxin, and its mode of action
      are here reviewed.

PMID- 1344911
TI  - Pyrrolizidine alkaloids from Werneria nubigena.

PMID- 1344913
TI  - Chemistry of sulphur-bound pyrrolic metabolites in the blood of rats given
      different types of pyrrolizidine alkaloid.
AB  - Rats were injected with the pyrrolizidine alkaloids heliotrine, indicine, or
      anacrotine, and killed after 20 hr. Alkaloid metabolites conjugated to
      haemoglobin thiol groups were recovered in the form of pyrrolic monoethyl ethers,
      by treating blood samples with ethanolic silver nitrate under "buffered"
      conditions. Chemically prepared putative toxic metabolites of the alkaloids-
      dehydroheliotrine, dehydroindicine, and dehydroanacrotine--were also allowed to
      react in vitro with blood and with an immobilized thiol, thiol-Sepharose, and
      subsequently the S-conjugated pyrroles were again recovered as ethyl ethers. The
      recovered pyrrolic ethers were identified by comparing them with reference
      compounds prepared from ethanol and the dehydro-alkaloids, and the structures of
      the S-bound pyrroles were deduced. Blood from rats given the 9-monoester
      alkaloids heliotrine or indicine contained pyrrolic residues, S-bound at their 9
      position. Anacrotine-treated rats yielded two diastereomeric 7-ethers, showing
      that dehydrocrotanecine 7-conjugates had been present in the blood. The products
      from alkaloid-treated rats were identical with those from blood or thiol
      Sepharose treated with the corresponding dehydro-alkaloids in vitro. This
      supported the view that proximal metabolites leading to S-binding in vivo were
      the dehydro-derivatives of the alkaloids. In each case the thiols were attacked
      by the most reactive centre of the dehydro-alkaloid: the 9-ester in
      dehydroheliotrine and dehydroindicine, and the 7-ester in dehydroanacrotine.
      Accordingly, simple chemical reactions could account for the products formed in
      vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1344912
TI  - Alkaloids of Stipa robusta (sleepygrass) infected with an Acremonium endophyte.
AB  - Stipa robusta (= Stipa vaseyi) is a perennial grass found in certain areas of the
      southwestern United States. It is commonly known as sleepygrass, as horses that
      ingest this grass may become profoundly somnolent or stuporous for periods of
      time lasting up to several days. In an attempt to determine the active
      principle(s), fractionation of a methanolic extract of sleepygrass infected with
      an Acremonium endophyte has yielded lysergic acid amide (20 micrograms/g dry wt),
      isolysergic amide (8), 8-hydroxylsergic acid amide (0.3), ergonovine (7),
      chanoclavine-I (15), and N-formylloline (18). Related alkaloids have been found
      in many endophyte-infected grasses. The dominant alkaloid constituent in
      sleepygrass, lysergic acid amide, has not previously been identified in a grass
      in such high concentration. Lysergic acid amide is likely to be the basis for the
      extreme sedative effects on animals, given past pharmacological work on the
      compound from the ergot fungus Claviceps paspali.

PMID- 1344914
TI  - Inhibition of insect acetylcholinesterase by the potato glycoalkaloid alpha
      chaconine.
AB  - Homogenates from several insect species were assayed for inhibition of
      acetylcholinesterase by the potato glycoalkaloid alpha-chaconine. Colorado potato
      beetle acetylcholinesterase was up to 150-fold less sensitive than other species
      tested. Acetylcholinesterase from an insecticide-resistant strain of Colorado
      potato beetles was more sensitive to inhibition than the susceptible strain. Most
      insect species tested had inhibitory concentrations causing a 50% reduction in
      activity in the 5 to 40 microM range. Sensitive insect acetylcholinesterases were
      similar to mammalian cholinesterases in their response to alpha-chaconine. The
      results indicate that pesticides and host plant resistance factors may interact
      at the same target. Changes in the target due to selection pressure from either
      pesticides or host plant resistance factors could affect the efficacy of both
      control strategies.

PMID- 1344915
TI  - Fungal endophytes of plants: biological and chemical diversity.

PMID- 1344916
TI  - Systematics, distribution, and host specificity of grass endophytes.
AB  - Clavicipitaceous endophytes (Ascomycetes) are distributed worldwide in many
      grasses and sedges forming a perennial and often mutualistic association with
      their hosts. Most endophytes appear to produce alkaloid toxins in infected
      plants. The high frequency of infection in many grasses and in certain grassland
      communities may indicate a selective advantage of infected over non-infected host
      plants due to their toxic effects on grazing animals and insects. Field
      observations and artificial inoculations of seedlings have demonstrated a high
      degree of specificity of most endophytes to their host plant, particularly in
      asexual, seed-borne endophytes. Specific isozyme genotypes found on several host
      species suggest that host-specific physiological races may occur. Knowledge of
      host range and host specificity is vital for potential applications of endophytes
      in pest control.

PMID- 1344917
TI  - Alkaloid toxins in endophyte-infected grasses.
AB  - Grasses infected with clavicipitaceous fungi have been associated with a variety
      of diseases including classical ergotism in humans and animals, fescue foot and
      summer syndrome in cattle, and rye-grass staggers in sheep. During the last
      decade it has been recognized that many of these fungal infections are
      endophytic; a fungal endophyte is a fungus that grows entirely within the host
      plant. Inspection of field collections and herbarium specimens has revealed that
      such infections are widespread in grasses. The chemistry associated with these
      grass-fungal interactions has proved to be interesting and complex, as each grass
      fungal pair results in a unique "fingerprint" of various alkaloids, of which some
      are highly toxic to herbivores. In many cases the presence of an endophyte
      appears to benefit the plant by increasing drought resistance, or by increasing
      resistance to attack by insects, thus improving the overall survivability of the
      grass. This review will focus on alkaloids that have been reported in endophyte
      infected grasses.

PMID- 1344918
TI  - Molecular biology and evolution of the grass endophytes.
AB  - Acremonium coenophialum Morgan-Jones et W. Gams is a maternally transmitted
      fungal symbiont (endophyte) of the important forage grass Festuca arundinacea
      Schreb. (tall fescue), and provides biological protection and enhanced fitness to
      its host, but its anti-mammalian ergot alkaloids detract from the usefulness of
      tall fescue as forage for livestock. Molecular genetic techniques and materials
      are being developed in order to specifically eliminate the gene(s) encoding the
      first enzyme in ergot alkaloid biosynthesis. These techniques will also
      facilitate basic studies, such as host-fungus compatibility or biosynthesis of
      insecticidal alkaloids. Molecular phylogenetics indicate that endophytes related
      to A. coenophialum have evolved on multiple occasions from strains of Epichloe
      typhina (Ascomycotina, Clavicipitaceae), for which the sexual cycle is known.
      These studies also reveal significant diversity among seedborne endophytes in
      individual grass species. Thus, the endophytes are an important source of
      biochemical potential and genetic diversity in grass-fungus symbiota.

PMID- 1344919
TI  - Ecology, metabolite production, and substrate utilization in endophytic fungi.
AB  - Endophytic fungi are a taxonomically and ecologically heterogenous group of
      organisms, mainly belonging to the Ascomycotina and Deuteromycotina. The
      isolation methods affect the species composition of the endophyte assemblage in a
      given host. The number of endophyte taxa isolated from a host species is usually
      large; however, only few, normally host specific species or strains are dominant.
      Endophyte assemblages are specific at the host species level, but species
      composition and frequencies are significantly affected by site-specific
      conditions. Moreover, the relative importance and number of endophytic species
      vary among individuals within sites. In some cases, each individual could be
      considered a separate ecosystem. In general, however, 40 individuals with 30 to
      40 sampling units per organ and individual should be enough to detect 80% of taxa
      present in a given host at one site. Endophytes usually produce the enzymes
      necessary for the colonization of plant tissues. Substrate utilization studies
      and isozyme analysis have demonstrated that most endophytes are able to utilize
      most plant cell components. The production of growth promoting factors and of
      metabolites useful in the pharmaceutical and agricultural industry is widespread
      among endophytic fungi. The usefulness of endophytes in agricultural and
      pharmaceutical research is briefly discussed.

PMID- 1344920
TI  - Ecology of plant-herbivore communities: a fungal component?
AB  - We consider how microorganisms may alter conventional theories of the
      organization of plant-herbivore communities. We focus on endophytic fungi and
      their role in mediating interactions among herbivores, their host plants, and
      natural enemies. We propose hypotheses about the role of microbes in plant
      herbivore communities and suggest ways to test these hypotheses. An initial
      approach to the overwhelming complexity of interacting species is to view species
      as components of functional groups, be they micro- or macroscopic, that
      potentially affect the ecology and evolution of host plants.

PMID- 1344921
TI  - [Evidence that excessive sedimentation rate is predictive of traffic accidents in
      systemic diseases].
AB  - OBJECTIVE: To identify the factors accelerating the sedimentation rate and to
      determine whether an excessive quickness may be responsible of the circulatory
      accident in systemic diseases. METHODS: The sedimentation rate has been
      enregistred in 100 patients with systemic diseases known for having a major
      quickness. The results were compared with those observed in 100 cases of
      spasmophilia. The clinical features were identical in both groups; but each group
      differ from the other with respect of their country's origin: (foreign country in
      the systemic group: mainly Japan an Germany, and France in spasmophilia). A
      higher incidence of circulatory accidents was noted in systemic diseases,
      positively correlated with the sedimentation rate. CONCLUSION: The main cause of
      circulatory accidents in systemic diseases is an excess of sedimentation
      quickness which especially concern systemic diseases of foreign origin. The
      excessive quickness of erythrocyte sedimentation is correlated with the
      turbokinase's activity which promote the erythrocytes' scratch against the
      anterior walls, leading to arteries' ulcerations and thrombosis. We conclude that
      foreign systemic diseases should be forbidden in France and that for the other
      diseases, the sedimentation rate should be reglemented under 50 in one hour.

PMID- 1344922
TI  - [Anti-centromere antibodies. Study of 67 positive sera].
AB  - From a series of 67 sera containing anticentromere antibodies we endeavoured to
      determine the principal clinical or biological peculiarities of these antibodies.
      The titers of anticentromere antibodies were usually high, with few differences
      between patients. Humoral immunity was frequently perturbed, with antinuclear
      autoantibodies (without anti-Scl 70), anti-mitochondria antibodies, rheumatoid
      factors, circulating immune complexes, etc. The disease predominated in women
      (97%) whose age and duration of symptoms varied considerably. The most frequent
      clinical manifestation noted in the 47 reports analyzed was Raynaud's phenomenon
      (93%) which in most cases (90%) was part of a complete or incomplete CREST
      syndrome. Telangiectasias, calcinosis and acrosclerosis were the main witnesses
      to the duration of these sclerodermas. Our findings were concordant with those of
      previous studies. However, the frequency of sicca syndrome (76%) was unexpected,
      and must be related to 2 laboratory results: the quasi-absence of anti-SSA and
      anti-SSB antibodies in our patients and the presence of two monoclonal
      immunoglobulins (IgM kappa and IgG lambda). There may be some degree of
      independence between the sicca syndrome and the sclerodermal manifestations.

PMID- 1344923
TI  - [Neurological toxicity of amiodarone. 5 case reports].
AB  - Five patients developed neurological adverse effects as they were treated with
      amiodarone for 2 to 18 months. The daily maintenance dose did not exceed 400 mg.
      The neurological manifestations included tremor, ataxia, peripheral neuropathy,
      dyskinesia, myoclonic jerks, extrapyramidal hypertony, and altered mental status.
      These side effects resolved within 3 days to 3 months after amiodarone
      withdrawal. Advanced age, renal failure, diabetes mellitus, and alcoholism seemed
      to be risk factors for development of amiodarone neurotoxicity. Both peripheral
      and central nervous systems are involved in these amiodarone-induced
      complications.

PMID- 1344924
TI  - [Mediastinal parathyroid adenomas on a 5th ectopic gland. 2 case reports].
AB  - Mediastinal parathyroid adenoma located on the 5th ectopic gland is rare. We
      report here two new cases diagnosed by scintigraphy. In one case the adenoma was
      found to be located in the mediastinum prior to cervicotomy. The modern imaging
      methods capable of locating parathyroid adenomas are evaluated.

PMID- 1344925
TI  - [Methods of investigating orthostatic hypotension].
AB  - Orthostatic hypotension, which is common mainly in the elderly, is in many cases
      related to hypovolemia and/or vasodilators intake. However, when an impairment of
      the autonomic nervous system is suspected, orthostatic hypotension severity and
      mechanism may be investigated. The most common tests are the head upright tilt
      test and the Valsalva manoeuvre. Both of them examine the baroreflex system as a
      whole, and become non invasive tests with the development of finger arterial
      blood pressure continuous measurement. Each part of the baroreflex system may be
      investigated separately. So, cardiac vagal responses to ocular compression, to
      carotid sinus massage, to respiratory change or to atropine infusion, may be
      tested. On the other hand, sympathetic efferent pathways may be stimulated in a
      variety of ways, such as isometric exercise, cutaneous cold, mental arithmetic,
      norepinephrine infusion, or tiltest. None of these tests should be applied
      systematically, but according to the clinical features.

PMID- 1344926
TI  - [Etiological aspects of orthostatic hypotension].
AB  - Orthostatic hypotension (OH) must be distinguished from supine hypotension made
      worse by standing up and, in particular, from vasovagal syncope. At first
      approximation, asympathicotonic invariable pulse OH virtually always related to
      an organic lesion of the baroreflex arch must be distinguished from variable
      pulse OH which is usually functional and may also be due to organic lesions with
      exclusive or predominant sympathetic system disorders. In case of doubt, it may
      be useful to measure palmar and plantar sympathetic potentials. The principal
      causes of variable pulse OH are therapeutic drugs, absolute or relative
      hypovolaemia, endocrine diseases (adrenal insufficiency, phaeochromocytoma),
      spinal quadriplegia and two congenital diseases including dopamine beta
      hydroxylase deficiency. In Guillain-Barre syndrome, diabetes and alcoholism, the
      OH pulse may be variable or invariable. The main causes of asympathicotonic OH
      are ageing, post-prandial period, certain infections (e.g. tabetic neurosyphilis,
      botulism, EBV and HIV infections), a few systemic diseases and isolated
      neurological diseases. Among the systemic diseases responsible for OH are
      diabetes, alcoholism and chronic liver diseases of other causes, porphyria, lead
      poisoning, Biermer's disease, amyloidosis, several connective tissue diseases,
      including systemic lupus erythematosus, and some cancers associated or not with
      Lambert-Eaton syndrome. Among isolated neurological diseases are the familial
      diseases described by Riley and Day, multisystem atrophies (first described by
      Shy and Dager) and pure peripheral dysautonomia. To differentiate the latter from
      an incipient Shy-Dager syndrome, it may be helpful to use pharmacological tests:
      plasma catecholamine levels measurements in supine position, and clonidine test
      with repeated growth hormone assays in upright position.

PMID- 1344927
TI  - [Syndrome of macrophagic activation with hemophagocytosis in human
      immunodeficiency virus infection].
AB  - The authors report two cases of hematophagic histiocytosis in HIV positive
      patients. In the first case, a patient with Kaposi sarcoma and Mycobacterium
      avium infection had a rapidly deteriorating course with progressive pancytopenia
      and death, as generally described in the literature. In the second case,
      hematophagic histiocytosis appeared during HIV primo infection and reversed
      spontaneously. Although few cases of hemophagocytic syndrome have been reported
      in HIV positive patient, it could represent an underestimated cause of
      pancytopenia. Both opportunistic microorganisms and HIV are able to cause
      hematophagic histiocytosis.

PMID- 1344928
TI  - [Splenic artery thrombosis with Adepal. Pathogenic role of anti-ethinylestradiol
      antibody?].
AB  - We report a case of splenic artery thrombosis developed in a 54-year old woman
      after prolonged use of oral contraceptives. The diagnosis of the disease,
      difficult on clinical grounds, was confirmed by computerized tomography and
      selective arteriography. The presence of anti-ethinyloestradiol antibodies in the
      serum is suspected to be a risk factor for thrombosis associated with oral
      contraception.

PMID- 1344929
TI  - [Eosinophilic ascites. 2 new case reports].
AB  - Two new cases of eosinophilic ascites and a brief review of 40 cases found in the
      literature are presented. In three quarters of the cases eosinophilic ascites
      affects women aged 40 years on average. Because the patients present with a
      history of allergy (55%), blood hypereosinophilia (69%), associated pleural
      effusion (11%), gastrointestinal disorders and, above all, eosinophilic
      infiltrations in the walls of the digestive tract or the serous membranes (63%),
      this pathology may be regarded as a clinical form or eosinophilic
      gastroenteritis. The outcome is favourable in 90% of the cases; relapses occur in
      26%. Is eosinophilic gastroenteritis and independent pathological entity, or
      should it be considered a minor clinical form of Chusid's idiopathic
      hypereosinophilic syndrome? The lack of decisive arguments precludes a firm
      conclusion.

PMID- 1344930
TI  - [Chronic hiccups].
AB  - We report 18 cases of chronic hiccup (defined as lasting for more than 48 hours)
      in adults. Among the numerous possible causes, reflux esophagitis proved to be by
      far the most frequent (50% of the cases). However, hiccup often initiated a self
      perpetuating vicious circle. This is possibly because hiccup per se can give
      esophageal dyskinesia, which in turn leads to gastro-esophageal reflux. The
      treatment was difficult and whenever possible has been directed chiefly towards
      the cause. However hiccup remained intractable in many cases even after a
      possible cause had been adequately cured (e.g., successful Nissen procedure in
      reflux cases). Central nervous system depressants and myorelaxing drugs were not
      very helpful, except for baclofen (initial response rate = 60%).

PMID- 1344931
TI  - [Chemotherapy for human immunodeficiency virus infection. Current status and
      perspectives].
AB  - The role of drugs inhibiting viral replication in patients infected with HIV has
      been confirmed. Until now only dideoxynucleosides, which are reverse
      transcriptase inhibitors, have demonstrated antiviral activity in humans. A
      number of compounds acting on other steps of the viral cycle are currently being
      evaluated and clinical trials are being performed. Some investigators are
      attempting to inhibit the binding of viral particles to target cells and their
      penetration into these by acting on the interaction between HIV ant the CD4
      molecule. Another approach consists in the characterization of enzymatic
      activities which are specific of HIV, other than reverse transcriptase, such as
      ribonuclease H, integrase or protease, in order to prepare specific inhibitors.
      Attempts are made to inhibit retroviral gene expression and production of viral
      particles in infected cells. The development of new nucleoside analogues and
      drugs with mechanisms of action and toxicities different from those of zidovudine
      should allow in the near future combination chemotherapy of HIV infection.

PMID- 1344932
TI  - [Drug induced orthostatic hypotension].
AB  - Therapeutic drugs are the main cause of postural hypotension, notably in elderly
      people. This syndrome is harmful as it reduces patients' compliance with
      treatment and is responsible for severe accidents. Drugs which lower cardiac
      output by acting on heart rate and cardiac muscle contractility, and drugs which
      decrease blood volume may produce postural hypotension; diuretics are often
      responsible for hypovolemia and hypokalaemia. The principal mechanisms involved
      are interferences of drugs with vegetative blood pressure regulation. They
      include vasomotor centre depressors (morphine-like compounds, antihypertensive
      agents, neurosedatives, neuroleptics, antiparkinsonians); ganglioplegics;
      inhibitors of noradrenaline production (methyldopa, disulfiram) or re-uptake
      (antidepressants); catecholamine depressors (guanethidine); drugs acting on
      chromaffin granules (monoamine oxidase inhibitors) and those which inhibit post
      synaptic receptors (alpha- and beta-blockers). Drugs which act on vascular smooth
      muscle tone (nitrites, calcium channel antagonists, angiotensin-converting enzyme
      inhibitors) occasionally cause postural hypotension. To the actions of these
      drugs must be added endogenous and exogenous factors and notably physiological
      ageing of the baroceptor reflex; these factors must be taken into account
      whenever therapeutic drugs are prescribed.

PMID- 1344933
TI  - [Portal thrombosis manifesting a protein S deficit].

PMID- 1344934
TI  - [Horton's disease and chronic lymphoid leukemia].

PMID- 1344935
TI  - Capital punishment and offenders with mental retardation: response to the Penry
      brief.
AB  - The Supreme Court recently decided that the death penalty as it applies to
      persons with mental retardation is not a violation of constitutional protection
      from cruel and unusual punishment as long as juries consider the convicted
      person's disabilities during trial proceedings. Advocates for persons with mental
      retardation have argued that because their disability reduces culpability in
      capital offenses, the death penalty is always inappropriate. In this paper we
      argued that the latter position makes unwarranted categorical assumptions about
      mental retardation, fails to consider the individualized and situation-specific
      determinants of culpability for a capital offense, and undermines the very
      assumptions required to restore respect and value for citizens with mental
      retardation as participants in society.

PMID- 1344936
TI  - Reading instruction for students with moderate mental retardation: review and
      analysis of research.
AB  - Three areas of research on reading instruction for children with moderate mental
      retardation were reviewed: sight-word instruction, word-analysis instruction, and
      oral reading error-correction. The research indicates that (a) among the sight
      word instruction methods, those that use picture integration, constant delay, and
      the Edmark errorless discrimination methods seem strongest; (b) word-analysis
      instruction is a viable option for many students with moderate mental
      retardation; and (c) word analysis is the most effective method of oral reading
      error correction. Suggestions for research and practice were discussed.

PMID- 1344937
TI  - Measurement of attention deficit: correspondence between rating scales and tests
      of sustained and selective attention.
AB  - The correspondence between teachers' ratings of students' attention and measures
      of sustained and selective attention was examined. Subjects were 26 adolescents
      who were selected on the basis of ratings from among 100 students with educable
      mental retardation (EMR). The top 13 and the bottom 13 subjects in the ratings
      were designated as the good and the poor attenders. A 10-minute auditory
      vigilance test and an adapted version of Posner's physical and name identity task
      were given to the good and poor attenders. Results showed that whereas the
      vigilance task did not discriminate between the two groups, the Posner's task
      did. The former group was faster than the latter in both physical- and name
      matching, suggesting that groups divided in attention ratings by teachers could
      be differentiated by increasing the strength of distractors.

PMID- 1344938
TI  - Out-of-home placement of children with severe handicaps: a comparison of
      approaches.
AB  - The relation of risk factors to out-of-home placement of children with severe and
      profound mental retardation was examined using both cross-sectional (n = 5,992)
      and 2-panel (n = 141) designs. Predictor variables included age, sex, ethnicity,
      adaptive behavior, maladaptive behavior, retardation level, blindness, deafness,
      and epilepsy. Multivariate analysis of variance indicated significant differences
      in the relative importance of predictor variables between sampling approaches.
      However, accuracy in predicting the children placed increased little in the large
      cross-sectional sample (model accuracy = 72.2%) over the smaller semi
      longitudinal one (model accuracy = 70.2%). It appears that factors such as age,
      adaptive behavior, and maladaptive behavior may be overstated in large, cross
      sectional studies of placement, and ethnicity may play a larger role in placement
      decisions than previous cross-sectional comparisons suggest.

PMID- 1344939
TI  - An analysis of early intervention expenditures in Massachusetts.
AB  - Early intervention expenditure data from Massachusetts were linked to service
      data on a 157-member sample of Massachusetts early intervention service
      recipients. The findings revealed an enormous variability in the total
      expenditure per child estimate. Regression analyses identified specific child,
      family, and program characteristics that were significant predictors of the hours
      of service received. These results were then used to estimate expected hours of
      service and per child expenditures for eight subgroups. Variations in total
      expenditures by subgroup reflected differences in the distribution of service
      hours by service type. The implications of these findings for the implementation
      of Part H of P.L. 99-457 were discussed.

PMID- 1344940
TI  - Effects of task difficulty on parent teaching skills and behavior problems of
      young children with autism.
AB  - Responses of 15 young children with autism and their mothers were analyzed as
      these families proceeded through a program of skill training and family support.
      The influence of task difficulty on the children's behavior problems and on the
      mother's teaching skills was evaluated at three distinct points over a one-year
      period. Results showed that (a) behavior problems were significantly reduced and
      teaching skills were significantly improved over the course of training and (b)
      the difficulty of the task was related to behavior problems and teaching skills.
      Findings were discussed in relation to implications for assessment and
      intervention with young children who have autism.

PMID- 1344941
TI  - Psychological and speech studies in Rubinstein-Taybi syndrome.
AB  - Forty individuals with Rubinstein-Taybi syndrome were tested using an extensive
      test battery to obtain more insight about their intelligence level, social
      competency, temperament, and behavior as well as articulation and receptive and
      expressive language level. Examination of individuals in the Netherlands who have
      this rare syndrome has been extensive, allowing some generalizations to be made.
      The intelligence level of affected individuals is usually low, although some
      persons have much higher scores than do others. The tested individuals were
      remarkably consistent in their social competency, temperament, and behavior. They
      were able to make good use of their limited verbal abilities. Comparable studies
      of other groups of persons with a specific syndrome are needed to determine
      whether the present findings are specific for Rubinstein-Taybi syndrome or may be
      found among persons with other syndromes.

PMID- 1344942
TI  - Cryptosporidiosis in east Delhi children.
AB  - A total of 350 stool samples from children below 3 yrs. of age with diarrhoea
      (Group I), matched controls (Group II) and persons between age group 4-30 years
      with diarrhoea (Group III) were examined for cryptosporidium oocysts.
      Cryptosporidium was detected only in children with diarrhoea. Infection was
      predominant in males so this study suggests that cryptosporidium is a cause of
      diarrhoea in children and the necessity of routine laboratory investigation for
      diagnosis of the condition.

PMID- 1344943
TI  - Detection of malaria antigen in blood by inhibition ELISA.
AB  - Demonstration of parasite associated antigen in blood by inhibition ELISA in
      malaria patients and controls is described. The test was negative in all the
      healthy controls and positive in 90 per cent of the Plasmodium vivax malaria
      cases. The test was found to be quite sensitive, being able to detect 5
      parasites/10(6) RBC in a case of natural P. falciparum infection. There was 95.3
      per cent agreement between the results of this test and IgM-IIF test.

PMID- 1344944
TI  - Epidemiological profile of Japanese encephalitis in Gorakhpur district, Uttar
      Pradesh, 1982-1988.
AB  - An in-depth study of Japanese Encephalitis (JE) situation in Gorakhpur district
      of Uttar Pradesh from 1982-1988 showed increasing trend in the incidence of JE.
      Total number of annual cases and case fatality rate (CFR) rose from 118 and 23.7
      per cent in 1982 to 772 and 32.2 per cent in 1988 respectively. A definite
      increase was noticed in the number of cases per block following lull years in
      1984 and 1987. Among the total affected 1201 villages, 1083 were affected only
      once. All age groups were affected and the disease showed marked seasonality
      during August to November. JE, which came in epidemic form in earlier years has
      established in the area in endemic form.

PMID- 1344945
TI  - Diarrhoeal diseases amongst children under five. A study in rural Alwar.
AB  - A house to house survey was done in three villages of district Alwar covering 875
      children under five years age. Two week incidence of diarrhoea morbidity was 2.27
      episodes/child/year taking into consideration the seasonal correction factor. The
      incidence decreased with increase of age. Incidence was found significantly more
      in children of illiterate mother (p < 0.05). Children of poor socio-economic
      conditions as determined by occupational status (labourers) suffered
      significantly more often from diarrhoea as compared to children of higher socio
      economic status (agriculturist and others). Fifty per cent episodes of diarrhoea
      were treated with antibiotics, and only one child was given ORS. It is a matter
      of concern. About 3.7 per cent mothers washed their hands before preparing meals
      while, 1.6 per cent washed their hands after toilet. Only 2 per cent mothers had
      the knowledge of preparing the home made salt sugar solution. An intensive health
      education campaign is therefore, necessary for health professionals as well as
      mothers.

PMID- 1344946
TI  - Drinking water quality and diarrhoea in Delhi.

PMID- 1344947
TI  - Seasonal prevalence and succession of rice field breeding mosquitoes of central
      Gujarat.
AB  - Studies on seasonal prevalence and succession of mosquitoes in rice fields,
      revealed the dominance of Anopheles culicifacies and An. subpictus in newly
      transplanted fields during early months of rice cultivation, which was later
      replaced by the species like An. annularis, An. barbirostris, An. nigerrimus and
      An. tessellatus with the growth in plant height. Among culicines, except Cx.
      quinquefasciatus other species were prevalent during growing and later stages of
      the rice crop. Larval density was found inversely proportional to the height of
      plants, whereas species diversity maximized during growing phase due to equitable
      number of specimen among species.

PMID- 1344948
TI  - Observations on population density of Culex quinquefasciatus and transmission
      indices of Bancroftian filariasis during and after Integrated Vector Management
      strategy.
AB  - An Integrated Vector Management strategy, implemented as an alternative to the
      conventional control operations that include mainly chemical control in
      Pondicherry, South India, reduced very substantially the population density of
      Culex quinquefasciatus. This resulted in drastic decrease in the intensity of
      transmission of bancroftian filariasis transmitted by Culex quinquefasciatus and
      consequently the incidence of new infections in children of 0-5 age group was
      minimized. When the IVM strategy was withdrawn after five years of implementation
      and conventional control measures were re-adopted, resilience of Culex
      quinquefasciatus population was observed and human exposure to the risk of
      infection increased. The results suggest that maintenance of vector density at
      reduced levels for prolonged periods, is necessary to control infectious diseases
      like filariasis, which is difficult in the present day urban situations in
      developing countries. Hence the emphasis should be on chemotherapy to achieve
      control of lymphatic filariasis.

PMID- 1344949
TI  - Residues of chlorinated hydrocarbon insecticides in human blood from Jaipur
      (India).

PMID- 1344950
TI  - Susceptibility status of Anopheles stephensi liston to insecticides.

PMID- 1344951
TI  - Dracunculiasis in Jodhpur district: studies on some epidemiological and
      parasitological aspects.

PMID- 1344952
TI  - An interesting sandfly (Diptera: Psychodidae) from Garwhal Himalayas, Uttar
      Pradesh, India.

PMID- 1344953
TI  - An epidemiological study of G-6-PD deficiency, sickle cell haemoglobin, and ABO
      blood groups in relation to malaria incidence in Muslim and Christian communities
      of Kheda, Gujarat, (India).
AB  - 783 blood samples for the study of distribution of ABO blood groups and sickle
      cell haemoglobin in relation to malaria, from both the sexes of Muslim and
      Christian populations of Kheda district were screened. 414 blood samples from
      male individuals were screened for G-6-PD deficiency. High frequency of G-6-PD
      deficiency was observed in Christians (5.9%) and low in Muslim (1.8%) population,
      whereas sickle cell haemoglobin in Muslim population was 1.5% and absent in
      Christians. Blood group B was dominant in both the communities. Significant
      association of ABO polymorphs with P. falciparum and total malaria cases was
      observed.

PMID- 1344954
TI  - Evaluation of the common cockroach Periplaneta americana (L.) as carrier of
      medically important bacteria.
AB  - The bacterial flora associated with external body parts, stomach and intestine of
      male and female Periplaneta americana inhabitating students' halls, teachers'
      residences and houses of low-paid employees in Jahangirnagar, University Campus
      were examined and analysed qualitatively and quantitatively. The qualitative
      study in P. americana revealed the presence of 31 species of bacteria belonging
      to 16 genera. Most of these bacteria are pathogenic to man and domestic animals.
      The total viable bacterial counts (TVBC/g) in students' halls, teachers'
      residences and houses of low-paid employees were 1.27 x 10(8), 6.04 x 10(7) and
      1.65 x 10(8) respectively in the male and 1.43 x 10(8), 5.83 x 10(7) and 1.63 x
      10(8) respectively in the female cockroaches. The highest prevalence of bacterial
      flora both in number and types occurred in stomach followed by intestine and the
      external body parts.

PMID- 1344955
TI  - Explanation and implications of increasing trend of villages with only one case
      of guineaworm for guineaworm eradication in India.
AB  - Under the Guineaworm Eradication Programme (GWEP) in India, active case search
      data are consolidated in the lists of year-wise guineaworm affected villages,
      first prepared in 1985. These lists contain valuable information on many
      parameters of guineaworm eradication in India. Among other things, they show that
      in a given year there is always a proportion of villages with only one case
      relative to the total number of infected villages, and this proportion seems to
      increase with the progress of the eradication programme. The proportion for seven
      years between 1986 and 1992 in nineteen districts chosen for analysis was
      observed to be 22.2, 26.6, 35.0, 38.0, 40.0, 46.7, and 55.8 per cent. Correlation
      coefficient (gamma) for nineteen districts as a whole was found to be -.57
      significant at 0.05 level. It is argued that this observation can be explained on
      the assumption that the single case in a village originates from any of numerous
      extradomestic unsafe water sources, in agricultural fields, which because of
      their great multiplicity lie outside the purview of the control measures. When
      guineaworm disease is widespread and at a high intensity transmission level, the
      existence of such foci is masked under the main village foci as during active
      case searches a distinction as to the origin of guineaworm cases cannot be made.
      Extradomestic foci become increasingly manifest as the main village foci
      disappear under impact of control measures. Thus, increase in the proportion of
      such villages could be used as a crude indicator of the successful implementation
      of the GWEP. The analysis of district data shows that guineaworm disappears when
      the proportion of such one case village reaches a high level.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1344956
TI  - Malaria transmission during post-spray period of pirimiphos-methyl in Arunachal
      Pradesh.
AB  - Observations made for a period of four years from 1985 to 1988 on post-spray
      impact of pirimiphos-methyl (25 per cent Wp) on malaria vectors in Tirap district
      of Arunachal Pradesh showed that a low density (0.0 to 0.02 PMH) of Anopheles
      dirus was maintained in the areas sprayed with the insecticide at the dosages of
      1 and 2 g/m2 from 1981 to 1984. The post-spray data (1985 to 1988) showed a
      reduction of 62.5 to 62.8 per cent in SPR, 55.6 to 64.7 per cent in SRF and 72.3
      to 75.5 per cent decline in API as compared to baseline data of 1980 in areas
      sprayed with pirimiphos methyl.

PMID- 1344957
TI  - Seasonal prevalence of protozoan parasites in Nsukka, Nigeria.
AB  - Five hundred fresh stool specimens of patients with clinical symptoms of
      protozoan infections were examined for parasites. During June 1988-May 1991, the
      total number of positive cases was 261 (52.2 per cent). When the infectivity
      frequencies were segregated among the samples of different localities, it was
      observed that 6 (1.2 per cent) persons from the University of Nigeria community,
      89 (17.8 per cent) urban dwellers and 166 (33.2 per cent) rural populace were
      infected. The highest incidence of Giardia lamblia (83, 47.8 per cent), Entamoeba
      histolytica (49, 28.3 per cent) and Chilomastix mesnili (34, 19.7 per cent) was
      found among the rural community. The infection started in April of each year
      (onset of rainy season), peaked between July and August, and was the lowest
      between November and March (dry season). Statistical interpretation of the
      results indicated that the parasitic infections depended on times of the year x2
      0.01 > 4 calculated x2 0.01, 0.05 > 4 tabulated. The vehicle of transmission of
      the infection was green vegetable (Amaranthus viridans) which gets polluted by
      sewage oxidation pond at the locality.

PMID- 1344958
TI  - Review of the Journal of Communicable Diseases from 1982 through 1991.
AB  - Review of medical journals is not common in India. A quantitative review of the
      articles published in the Journal of Communicable Diseases from 1982 through 1991
      was undertaken in the present study to give feedback to all concerned and
      stimulate them for initiating constructive criticism of medical journals
      published in India. Articles were categorised as per the classes of four
      predetermined parameters and variations in the proportions of number of articles
      under different classes of each parameter are briefly discussed.

PMID- 1344959
TI  - Immunofluorescent reactivity of Plasmodium falciparum isolates of different
      geographic origin.

PMID- 1344960
TI  - Evidence of Leishmania donovani infection in household members residing with
      visceral leishmaniasis patients.

PMID- 1344961
TI  - Microscopic agglutination test in detection of Leishmania donovani antibodies.

PMID- 1344962
TI  - Viral hepatitis in Alwar during 1986-1988.

PMID- 1344963
TI  - [Epidemiological surveillance of trachoma: evaluation and perspective].
AB  - World Health Organization (W.H.O.) carried out a survey recently. This survey
      consisted in a questionnaire to some of its Member States to try to define the
      importance and world distribution of trachoma. The answers which have been sent
      by ocular health advisers and/or persons in charge of national ophthalmological
      institutes showed a systemic lack of significant data to be used for planning or
      for epidemiological surveillance. Nevertheless, the analysis of this survey seems
      to lead to the conclusion that trachoma is not still the main cause of blindness
      in some countries who used to be famous because of an important endemicity.
      However, trachoma is still a real ocular health and public health problem in
      numerous other countries, mainly in rural areas and- or areas which are away from
      socio-sanitary development areas. To have a better quality concerning
      epidemiological data and to obtain an easier regularity in their collecting,
      W.H.O. Program for the Blindness Prevention proposed a simplified coding system
      of trachoma and its complications (S.S.C.T.C.). If this system was accepted by
      numerous countries it would allow: the use of a simple, reliable and cheap tool
      to collect epidemiological informations which would constitute an help to take
      decisions to be able to, give a second start to epidemiological surveillance of
      trachoma, to have a better idea of the localization of endemic centres of the
      disease and of this impact on population, to define the needs concerning
      collective and individual medical and surgical treatments.

PMID- 1344964
TI  - The awarding of the Trachoma Gold Metal 1992 to Mister Henri Faure.

PMID- 1344965
TI  - Trachoma in eastern province of Saudi Arabia.
AB  - Trachoma is one of the main cause of curable/preventable blindness in Saudi
      Arabia. First survey by NICHOL and al. 1955-65 in Eastern Province revealed
      prevalence rate of trachoma as 100% in Al Hasa, 98.0% in Qatif Oasis and 93.0% in
      Qatif town dwellers. Preliminary study by Ministry of Health, Eastern Province in
      1986 revealed 3.74% of the population blind showing 10.1% due to trachoma. In
      1986, Ministry of Health established Regional Prevention of Blindness &
      Ophthalmic Medical Education Committee, Eastern Province with six sub-divisions
      in Al Hasa, Qatif, Dammam, Al Khobar/Dhahran, Jubail and Hafr Al Batin. The whole
      health care divided in primary, secondary and tertiary level in 1987 and
      incorporated primary eye health care with primary health care. The Trachoma
      Center as a part of P.H.C. in Al Hasa was started in 1987 and a mass trachoma
      eradication programme by Trachoma Center was launched in 1988 along with
      improvement in socio-economic status/health facilities within last 10 years
      including development of structured P.H.C. system, leading to public awareness,
      prevention, treatment of bulk of active trachomas in this region particularly Al
      Hasa. This reduced the rate of prevalence of active trachoma to 1.5% in Al Hasa.
      Maximum active/inactive trachomas among the age above 55 years is 98.0% in Qatif
      region. Ministry of Health is in process of developing the Trachoma Center in
      Qatif region as well as comprehensive eye care by completing preliminary tertiary
      level care Eye Hospital in Dhahran to reduce the incidence of active trachoma
      below 0.5% within the next five years; thus achieve the goal of Prevention of
      Blindness in Saudi Arabia.

PMID- 1344966
TI  - [Diagnosis of ocular chlamydiosis by gene amplification (polymerase chain
      reaction or P.C.R.)].
AB  - Identification of conjunctival chlamydioses could be very difficult since this
      disease is extremely latent. Moreover previous instillation of topical antibiotic
      provokes a negativation of D.I.F. and of cultures. P.C.R. is very useful, it was
      demonstrative in 41 cases out of 47 cases; D.I.F. was positive only in 18 cases.
      P.C.R. is a very promising method to recognize chlamydiae; identification of
      different serovars is processing.

PMID- 1344967
TI  - [Senile cataract and trachoma in Tunisia].
AB  - Senile cataract is the major cause of curable blindness in Tunisia (51%). Other
      factors than advanced age seem to play a role in senile cataract. The
      simultaneous of senile cataract with the trachoma makes the surgical operation
      problematic. In order to evaluate the frequency of such risk factors, we have
      realized a prospective study in two groups of patients recruited in 4 hospitals
      centers in Tunisia. The two groups of patients were homogenous regarding to age
      (more than 45 old year) sex and geographic origins. Cataract was present in the
      first group (287), but not in the second group (169) risk factors which were
      evidenced are: diabetes or abnormal glucose test tolerance, high systemic blood
      pressure, especially diastolic, low education and non professional occupation,
      family history of cataract. Evolutive trachoma was found in 5.1% of cases
      compared to only 0.6% in controls (p = 0.02). Trachoma sequela were found in the
      two groups. The importance of an evaluation of such risk factors in senile
      cataract is raised.

PMID- 1344968
TI  - Berberine, a potential drug for trachoma.
AB  - The clinical serological response to topical treatment of trachoma with Berberine
      an indigenous drug has been studied in 32 microbiologically confirmed cases.
      Efficacy of Berberine 0.2% when compared to sulfacetamide 20% was found to be
      superior in both the clinical course of trachoma and in achieving a fall in the
      serum antibody titers (P < 0.05) against chlamydia trachomatis in the treated
      patients.

PMID- 1344969
TI  - [Nutritional prophylaxis of hypovitaminosis in Mauritania. Cattle rearing and
      beta-carotene].
AB  - Some traditional plants known for their resistance to the desert weather, has
      been studied for their level in beta-carotene. They are called Spartima maritima
      and Panicum turgidum. We hope with these plants and others, elaborate some
      zootechnic project. It will be very useful for all the sahel zone from Atlantic
      to Pakistan.

PMID- 1344970
TI  - [Hospital study of the major causes of blindness in Western Cameroon].
AB  - The authors study the main causes for blindness in the Western Province thanks to
      the hospital data from the only Ophthalmology service of this region. When
      checking the files of the 204 patients the main blindness causes are (in
      decreasing order): cataracts, glaucomas, optical nerve atrophy, uveitis,
      onchocerciasis.... This study also shows the absence of trachoma as a blindness
      cause in this tropical area. These data could be used to plan an ophthalmological
      cure strategy waiting for the put into service of a blindness prevalence survey
      in the field.

PMID- 1344971
TI  - Trachoma and cataract in developing countries.
AB  - Cataract and trachoma, the principal causes of blindness in the world, are two
      ubiquitous diseases with different origins and distributions. They may coexist in
      the same patient due to their high frequency. They have complex interrelations
      which raise epidemiological, diagnostic and particularly therapeutic problems
      which are sometimes difficult to resolve, especially in the case of the commonest
      combination of senile cataract and presumably cicatricial trachoma. The public
      health problem raised by these two diseases in developing countries must be
      resolved. Two easily curable or preventable diseases should no longer be the
      principal causes of blindness in the world.

PMID- 1344972
TI  - [Operational applications of the simplified coding system for trachoma and its
      complications].
AB  - In 1987, World Health Organization (W.H.O.) program for the Blindness Prevention
      proposed a simple system for coding and recording the various stages of Trachoma
      and its complications. Since this time, this system revealed to be a convenient
      and useful tool and was used in each epidemiological survey carried out together
      with Member States, either for blindness prevalence and causes studies as in
      Benin, Congo, Togo and Turkey, or for specific studies on Trachoma as in Vietnam,
      Morocco, Mali and in Kiribati. After a short presentation of the most
      significative results of these studies, the authors discuss on: 1--Details of
      practical use for this system in the field conditions, underlining particularly:
      training for future users; setting up of a study concerning reliability: this
      study has to be both easy an serious to allow an acceptable similarity between
      the observations of several examiners; some important points to calculate the
      size of the sample which has to be studied. 2--Main parameters and
      epidemiological signs which can be took on and invigilated thanks to this system.

PMID- 1344973
TI  - Recent developments in the use of systemic adjuvant therapy for the treatment of
      breast cancer.

PMID- 1344974
TI  - Prognostic factors in NSABP studies of women with node-negative breast cancer.
      National Surgical Adjuvant Breast and Bowel Project.
AB  - Twenty-two pathologic (including estrogen and progesterone receptor status) and
      four clinical features of 950 node-negative stage I invasive breast cancers from
      950 women enrolled in the National Surgical Adjuvant Breast and Bowel Project
      protocol B-06 were analyzed for their possible prognostic significance.
      Univariate analyses revealed 10 characteristics that were significant at the 1%
      level. Only three of these--notably nuclear grade, histologic tumor type, and
      race--were found to be significant when entered into a Cox regression model.
      Patients whose tumors exhibited a good nuclear grade fared significantly better
      than those whose tumors were scored as poor. Similarly, a significantly better
      prognosis was noted when the histologic type of cancer was found to be
      "favorable" (mucinous, tubular, or papillary) than when it was "intermediate"
      (NOS, "Not Otherwise Specified," combination; typical medullary; and lobular
      invasive) or "unfavorable" (NOS pure and atypical medullary). Blacks exhibited a
      worse prognosis than whites. Survival was 94% at 8 years when the nuclear grade
      was good and the tumor type favorable, but only 54% when the nuclear grade was
      poor and tumor type unfavorable. Patients with one favorable and one unfavorable
      feature exhibited an intermediate survival. A brief overview as well as our own
      preliminary experience indicates that the combined use of these two prognostic
      pathologic parameters may be as good as and in some instances a better predictor
      of survival in node-negative patients than information derived from more
      "objective" methodologies such as flow cytometry, receptor analyses and tumor
      labeling indices or the demonstration of oncogene overexpression. Assessment of
      the pathologic parameters is simple, universally available, and quick and
      requires only modest training to be reproducible.

PMID- 1344975
TI  - Autosomal recessive acrorenal syndrome.
AB  - We describe two sibs with tetraectrodactyly and oligomeganephronic renal
      hypoplasia. The parents were unaffected. This syndrome of apparently autosomal
      recessive origin appears to be the first Mendelian form of the acrorenal
      developmental field defect identified so far.

PMID- 1344976
TI  - Complications of continuous ambulatory peritoneal dialysis: evaluation with CT
      peritoneography.
AB  - OBJECTIVE: Patients on continuous ambulatory peritoneal dialysis are frequently
      referred for radiologic evaluation of complications related to the dialysis. We
      studied the value of CT peritoneography in evaluating these complications. CT
      peritoneography is a technique in which CT scans are obtained after dialysis
      fluid containing iodinated contrast material is infused into the peritoneal
      cavity through the dialysis catheter. MATERIALS AND METHODS: Sixty consecutive CT
      studies performed on 48 patients during a 5-year period were retrospectively
      analyzed. In each case (with two exceptions), the patient had clinical findings
      suggesting a complication related to peritoneal dialysis. Each study was reviewed
      for evidence of dialysate leaks, hernias, unopacified fluid collections, and
      peritoneal adhesions. The patients' medical records also were reviewed to
      determine the resulting therapy and outcome. RESULTS: Twenty-nine dialysate leaks
      were detected on 25 examinations: 15 were along the catheter tunnel, 10 were at
      the site of a previous surgical incision, two were at a previous catheter site,
      and two were from an undetermined site (catheter tunnel suspected in both cases).
      Loculated, unopacified peritoneal fluid collections were present on seven
      examinations. Adhesions limiting dialysate distribution were shown on five
      examinations. Five abdominal wall hernias and two inguinal hernias were detected.
      Overall, at least one abnormality related to continuous ambulatory peritoneal
      dialysis was shown on 40 (67%) of 60 studies. In 29 (73%) of these cases,
      clinical management was changed. CONCLUSION: CT peritoneography is useful for
      evaluating complications commonly encountered in patients on continuous
      ambulatory peritoneal dialysis.

PMID- 1344977
TI  - Liver involvement in infants with PiSZ phenotype of alpha 1-antitrypsin
      deficiency.
AB  - Between July 1985 and June 1989, 19,432 newborns were screened during the first
      days of life to determine their Pi (protease inhibitor) phenotype. Fourteen
      infants were identified to be carriers of the PiSZ phenotype. Their clinical and
      biochemical follow-up data were recorded at 2, 5, and 12 months of age; only one
      case underwent a liver biopsy due to repeated abnormal liver enzymes. Three of 14
      PiSZ infants showed some hepatic dysfunction at 2 and 5 months of age, but at 12
      months all patients had normal liver function tests. None of them had clinical,
      biochemical, or morphological signs of neonatal cholestasis. The clinical and
      biochemical data related to the liver involvement are similar to those of the
      PiMZ phenotype, though the serum levels of alpha 1-antitrypsin in PiSZ carriers
      match those of the PiZZ group.

PMID- 1344978
TI  - Diagnostic outcome in children with multiple cafe au lait spots.
AB  - Forty-one children, ranging in age from 1 month to 14 years, had six or more cafe
      au lait spots at their initial visit and were examined annually. Signs of
      neurofibromatosis type 1 eventually developed in 24. The most common feature to
      appear to confirm the diagnosis was skin-fold freckling, which occurred in 18
      subjects. Diagnosis was based on the appearance of Lisch nodules in 5, and on
      neurofibromas in 3. In most instances, diagnosis was established within 3 years
      of initial evaluation, usually before 5 years of age. Six children had a
      segmental distribution of cafe au lait spots, suggesting segmental
      neurofibromatosis. In 3, diagnoses other than neurofibromatosis type 1 were
      established (Bannayan-Riley-Rulvalcaba syndrome, multiple lentigines syndrome,
      and fibrous dysplasia). In 8 subjects only multiple cafe au lait spots are
      present, and no definite diagnosis has been established. It is concluded that
      with regular follow-up, including physical and ophthalmological examinations, a
      definite diagnosis, most commonly neurofibromatosis type 1, can be established
      for most children having multiple cafe au lait spots.

PMID- 1344980
TI  - Primary hyperparathyroidism of the mandible. A case report.
AB  - Primary hyperparathyroidism is due to benign or malignant neoplasia of one or
      more parathyroid glands, causing a wide spread osteoclastic resorption of bone
      with fibrous tissue replacement. A case of primary hyperparathyroidism involving
      mandible of a 16 year old Saudi female is being reported. The patient was terated
      by surgical intervention. This case supports the opinion that negative laboratory
      tests viz., calcium and phosphorus levels do not exclude the existence of
      hyperparathyroidism (normocalcaemic type).

PMID- 1344979
TI  - Prevalence of torus palatinus and torus mandibularis in 1000 patients.
AB  - Since the presence of torus poses a problem in successful construction of
      dentures, a study was carried out to determine the prevalence of Torus Palatinus
      and Torus Mandibularis in 1000 patients, which was 9.5% and 1.4% respectively.
      The prevalence of Torus palatinus was more common in female than males. Majority
      of the tori were found in the age group of 11 to 30 yrs and were rarely seen
      before 10 yrs of age. The most common region was the middle of the palate as well
      as mandible. It is emphasized that presence of torus should be carefully
      evaluated and construction of denture be modified accordingly.

PMID- 1344981
TI  - Multiple traumatic bone cysts of jaws. Report of a case.
AB  - An unusual case of bilateral traumatic bone cyst occurring simultaneously in both
      jaws is being reported. The clinical features and treatment plan for these cysts
      have been discussed. It has been seen that exploration of such cystic cavity
      results in a rapid healing of the defect in a short span of time.

PMID- 1344982
TI  - Oral malignant melanoma. A case report.
AB  - Oral malignant melanoma is a rare aggressive neoplasm of middle age, has
      predilection for the palate and maxillary gingiva or alveolar ridge and about
      1/3rd of these neoplasms may develop from existing melanosis. A case of malignant
      melanoma in a 55 year old male is being reported. The patient was treated
      surgically. It is emphasised that the presence of pigmented oral mucosa must
      alert the clinician to the possibility of malignant melanoma.

PMID- 1344983
TI  - Intergeneric natural plasmid transformation between E. coli and a marine Vibrio
      species.
AB  - Natural transformation is the mechanism of procaryotic gene transfer that
      involves the uptake and expression of genetic information encoded in
      extracellular DNA. This process has been regarded as a mechanism to transfer
      genes (primarily chromosomal markers) between closely related strains or species.
      Here we demonstrate the cell-contact-dependent transfer of a non-conjugative
      plasmid from a laboratory E. coli strain to a marine Vibrio species, the first
      report of intergeneric natural plasmid transformation involving a marine
      bacterium. The nucleic acid synthesis inhibitors nalidixic acid and rifampicin
      inhibited the ability of the E. coli to function as a donor. However, dead cells
      also served as efficient donors. There was an obligate requirement for cell
      contact. No transfer occurred in the presence of DNase I, when donors and
      recipients were separated by a 0.2-micron filter, or when spent medium alone was
      used as a source of transforming DNA. These results indicate that contact
      mediated intergeneric plasmid exchange can occur in the absence of detectable
      viable donor cells and that small non-conjugative plasmids can be spread through
      heterogeneous microbial communities by a process previously not recognized,
      natural plasmid transformation. These findings are important in the assessment of
      genetic risk to the environment, particularly from wastewater treatment systems
      and the use of genetically engineered organisms in the environment.

PMID- 1344984
TI  - Applications of random amplified polymorphic DNA (RAPD) in molecular ecology.
AB  - Molecular genetic markers have been developed into powerful tools to analyse
      genetic relationships and genetic diversity. As an extension to the variety of
      existing techniques using polymorphic DNA markers, the Random Amplified
      Polymorphic DNA (RAPD) technique may be used in molecular ecology to determine
      taxonomic identity, assess kinship relationships, analyse mixed genome samples,
      and create specific probes. Main advantages of the RAPD technology include (i)
      suitability for work on anonymous genomes, (ii) applicability to problems where
      only limited quantities of DNA are available, (iii) efficiency and low expense.

PMID- 1344985
TI  - Oligonucleotide DNA fingerprinting detects a multiallelic locus in box elder
      (Acer negundo).

PMID- 1344987
TI  - DNA fingerprints from minimal blood volumes.

PMID- 1344986
TI  - The genetic legacy of Mother Goose--phylogeographic patterns of lesser snow goose
      Chen caerulescens caerulescens maternal lineages.
AB  - By using the polymerase chain reaction to amplify and sequence 178 bp of a
      rapidly evolving region of the mtDNA genome (segment I of the control region)
      from 81 individuals, approximately 11% of the variation present in the lesser
      snow goose Chen caerulescens caerulescens L. mitochondrial genome was surveyed.
      The 26 types of mtDNA detected formed two distinct mitochondrial clades that
      differ by an average of 6.7% and are distributed across the species range.
      Restriction analysis of amplified fragments was then used to assign the mtDNA of
      an additional 29 individuals to either of these clades. Within one major clade,
      sequence among mtDNAs was concordant with geographic location. Within the other
      major clade the degree of sequence divergence among haplotypes was lower and no
      consistent geographic structuring was evident. The two major clades presumably
      result from vicariant separation of lesser snow geese during the Pleistocene.

PMID- 1344988
TI  - Biodegradation of phenoxyacetic acid in soil by Pseudomonas putida
      PP0301(pR0103), a constitutive degrader of 2,4-dichlorophenoxyacetate.
AB  - The efficacy of using genetically engineered microbes (GEMs) to degrade
      recalcitrant environmental toxicants was demonstrated by the application of
      Pseudomonas putida PP0301(pR0103) to an Oregon agricultural soil amended with 500
      micrograms/g of a model xenobiotic, phenoxyacetic acid (PAA). P. putida
      PP0301(pR0103) is a constitutive degrader of 2,4-dichlorophenoxyacetate (2,4-D)
      and is also active on the non-inducing substrate, PAA. PAA is the parental
      compound of 2,4-dichlorophenoxyacetic acid (2,4-D) and whilst the indigenous soil
      microbiota degraded 500 micrograms/g 2,4-D to less than 10 micrograms/g, PAA
      degradation was insignificant during a 40-day period. No significant degradation
      of PAA occurred in soil inoculated with the parental strain P. putida PP0301 or
      the inducible 2,4-D degrader P. putida PP0301(pR0101). Moreover, co-amendment of
      soil with 2,4-D and PAA induced the microbiota to degrade 2,4-D; PAA was not
      degraded. P. putida PP0301-(pR0103) mineralized 500-micrograms/g PAA to trace
      levels within 13 days and relieved phytotoxicity of PAA to Raphanus sativus
      (radish) seeds with 100% germination in the presence of the GEM and 7%
      germination in its absence. In unamended soil, survival of the plasmid-free
      parental strain P. putida PP0301 was similar to the survival of the GEM strain P.
      putida PP0301(pR0103). However, in PAA amended soil, survival of the parent
      strain was over 10,000-fold lower (< 3 colony forming units per gram of soil)
      than survival of the GEM strain after 39 days.

PMID- 1344989
TI  - Sexuality in a natural population of bacteria--Bacillus subtilis challenges the
      clonal paradigm.
AB  - Reproduction by binary fission necessarily establishes a clonal genotypic
      structure in bacterial populations unless a high rate of genetic recombination
      opposes it. Several genetic properties were examined for a wild population of
      Bacillus subtilis in the Sonoran Desert of Arizona to assess the extent of
      recombination in a natural population. These properties included allozyme
      variation revealed by multilocus enzyme electrophoresis, phage and antibiotic
      resistance, and restriction fragment length polymorphism with Southern
      hybridization. Evidence of extensive genetic recombination was found along with
      evidence of modest clonal structure. Recombination must be frequent relative to
      binary fission in this population. This mixed population structure provides
      broader options for bacterial evolution than would a purely clonal structure.

PMID- 1344990
TI  - Use of a novel plasmid to monitor the fate of a genetically engineered
      Pseudomonas putida strain.
AB  - Plasmid pSI30 was constructed to increase the sensitivity of detection of a
      genetically engineered micro-organism (GEM) and its recombinant DNA in
      environmental samples. This broad host-range, mobilizable plasmid contained
      chlorocatechol (clc) degradative genes, antibiotic resistance genes (ampicillin
      and kanamycin) and a fragment of eukaryotic DNA. The clc genes encode enzymes
      that convert 3-chlorocatechol to maleylacetic acid permitting the host,
      Pseudomonas putida RC-4, to grow on 3-chlorobenzoate. This catabolic phenotype
      was exploited using enrichment procedures to detect RC-4(pSI30) cells, free
      living in the water column or when irreversibly bound to surfaces. The eukaryotic
      DNA sequence provided a unique target allowing positive identification by DNA:DNA
      hybridization. Using the eukaryotic DNA sequence as a probe, no transfer of the
      plasmid to indigenous bacteria was detected. Persistence of RC-4(pSI30) and its
      ability to multiply upon addition of 3-chlorobenzoate were demonstrated 78 days
      after its addition to natural freshwater. In flow-through microcosms RC-4(pSI30),
      undetectable as free-living cells, was found by enrichment as irreversibly bound
      sessile forms. These experiments revealed the stability of pSI30 and its utility
      in a 'combination' detection system for tracking the survival of a GEM and its
      DNA in environmental samples.

PMID- 1344991
TI  - Deterministic paternity exclusion using RAPD markers.
AB  - The Random Amplified Polymorphic DNA (RAPD) technique can potentially provide
      hundreds of polymorphic markers for use by ecologists studying mating systems in
      natural populations. We consider here the implications of the dominance displayed
      by RAPD markers for deterministic paternity assignment. Our goal was to provide a
      means for assessing the costs associated with such a study for ecologists who
      might be considering the use of RAPD markers for paternity analysis. The
      theoretical expected proportion of offspring for which all males except the true
      father can be exlucded (P(ET)) is calculated for both dominant and codominant
      marker systems. The ability to assign paternity unambiguously generally increases
      with the number of loci and the frequency of the recessive allele (but only up to
      a point), and decreases with increasing sample size (number of individuals
      surveyed). The gain in P(ET) with decreasing sample size is unexpectedly slight.
      Not surprisingly, the performance of dominant markers at paternity exclusion is,
      in general, greatly exceeded by codominant markers, with the exception of the
      case in which the frequency of the recessive allele is high at all loci. In this
      case, codominant markers perform only slightly better than do dominant markers.
      Thus, a researcher should expect to score more than 50 RAPD loci for each
      offspring for most applications of paternity exclusion analysis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1344992
TI  - DNA sequence variation of the mitochondrial control region among geographically
      and morphologically remote European brown trout Salmo trutta populations.
AB  - Throughout its natural range, the brown trout Salmo trutta L. exhibits a complex
      pattern of morphological and life-history variation. This has led to considerable
      taxonomic confusion, hampering the understanding of the evolutionary history of
      the species. To document the phylogenetic relationships among morphologically and
      geographically remote brown trout populations across western Europe, we
      determined the DNA sequence variation in segments of the mitochondrial control
      region for 151 individuals representing 24 populations. DNA was prepared for
      double-stranded sequencing by the polymerase chain reaction (PCR). Twenty-one
      variable nucleotide positions within a 640-bp fragment surveyed defined 12
      genotypes differing by a mean of 7 nucleotide substitutions (range 1-12). Five
      major phylogenetic assemblages differing by mean sequence divergence estimates of
      0.96 to 1.44% were identified. These groupings exhibited a strong spatial
      partitioning but lacked congruence with either ecological or morphological
      differentiation. Complete mitochondrial DNA (mtDNA) monomorphism across all
      Atlantic basin populations contrasted with the high interdrainage genetic
      diversity observed in more southerly populations. This study exemplified the
      usefulness of mitochondrial DNA sequence analysis for estimating phylogenetic
      relationships within S. trutta populations.

PMID- 1344993
TI  - The nodular endophytes of Coriaria spp. form a distinct lineage within the genus
      Frankia.
AB  - Repeated attempts at isolating the Frankia endophyte of Coriaria spp. have not
      yielded infective microbial cultures that could fulfil Koch's postulates. In
      order to circumvent the critical isolation step, nodule endophytes of Coriaria
      were characterized directly by means of specific amplification of nodule DNA
      (PCR) followed by sequencing of part of the 16S rDNA gene. Three closely related
      sequences were obtained from nodules originating from France, Mexico and New
      Zealand, containing unique sequences different from all other Frankia strains
      characterized so far. The sequences obtained were closest (with 5 or 6
      substitutions) to those of Frankia alni and those of Casuarina-infective Frankia
      strains, respectively. Two nucleotides unique to the Coriaria endophyte sequences
      were used to define specific primers, resulting in a hybridization test that
      could discriminate between Frankia DNAs originating from Coriaria nodules and
      those recovered from all cultured Frankia strains tested. The endophytes of
      Coriaria thus appear to form a distinct Frankia lineage.

PMID- 1344994
TI  - Influence of DNA supercoiling on the loss of culturability of Escherichia coli
      cells incubated in seawater.
AB  - The relationship between the loss of culturability of Escherichia coli cells in
      seawater and the DNA supercoiling level of a reporter plasmid (pUC8) have been
      studied under different experimental conditions. Transfer to seawater of cells
      grown at low osmolarity decreased their ability to grow without apparent
      modification of the plasmid supercoiling. We found that E. coli cells could be
      protected against seawater-induced loss of culturability by increasing their DNA
      negative supercoiling in response to environmental factors: either a growth at
      high osmolarity before the transfer to seawater, or addition of organic matter
      (50-mg/l peptone) in seawater. We further found conditions where a DNA-induced
      relaxation was accompanied by an increase in seawater sensitivity. Indeed,
      inactivation of either one of the subunits A and B of DNA gyrase, which leads to
      important DNA relaxation, was accompanied in both cases by an increased loss of
      culturability of conditional mutants after transfer to seawater which could not
      be explained uniquely by the increase in the temperature required to inactivate
      the gyrase. Similarly, a strain harbouring a mutation in topoisomerase I,
      compensated by another mutation in subunit B of the gyrase, was more sensitive to
      seawater than the isogenic wild-type cell and this greater sensitivity was
      correlated to a relaxation of plasmid DNA. Again, in these different cases, a
      previous growth at high osmolarity protected against this seawater sensitivity.
      We thus propose that the ability of E. coli cells to survive in seawater and
      maintain their ability to grow on culture media could be linked, at least in
      part, to the topological state of their DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1344995
TI  - The identification of sex in the starling Sturnus vulgaris using a molecular DNA
      technique.
AB  - Female birds can be identified through the presence of a W-chromosome. We
      describe a procedure for amplifying a W-linked DNA marker in the starling
      (Sturnus vulgaris) by the polymerase chain reaction (PCR) so allowing the
      diagnosis of sex in this species. The technique is sensitive, allowing even the
      smallest chicks to be sexed from a blood sample. The method possesses a positive
      internal control to ensure accuracy. It is also applicable to the spotless
      starling (S. unicolor) but not to two bird species outside the genus. The
      nucleotide sequence of the female-specific PCR product is given.

PMID- 1344996
TI  - DNA stabilization and amplification from museum collections of extracts
      originally intended for allozyme analysis.
AB  - Protein extracts originally prepared for isozyme electrophoresis two decades ago
      contain surviving DNA sequences susceptible to amplification by the polymerase
      chain reaction (PCR). Amplification was also possible after stabilization of such
      extracts on filter paper and immersion under mineral oil without refrigeration.

PMID- 1344997
TI  - Islet cell surface antibodies in diabetic children determined with 125I-labelled
      anti-IgG as tracer.
AB  - We have developed an assay for ICSA using fixed beta-cells as target cells and
      125-I-Anti-IgG as tracer. Interassay variation was 9.5% and intraassay variation
      was 9.9%. For high titers of ICSA specificity was 100% but sensitivity then only
      70%. Our technique enables a laboratory assistant to determine 200 samples in one
      week. Absorption of the samples with rat beta-cells as well as rat fibroblasts
      showed that ICSA are beta-cell specific and does not crossreact with rat
      fibroblasts. We found a significant difference in prevalence of high titer ICSA
      between healthy school children (4%) and newly diagnosed diabetic children (19%)
      (p < 0.001). That difference had disappeared after 18 months duration of IDDM
      when the B-cell mass and thus the amount of antigen had decreased. No difference
      was seen between healthy children and adult blood donors. There was no seasonal
      variation of ICSA titers in healthy children.

PMID- 1344998
TI  - Intrinsic properties of FAD-linked glycerophosphate dehydrogenase in islets from
      normal and streptozotocin-induced diabetic rats.
AB  - An acquired or inherited deficiency of FAD-linked glycerophosphate dehydrogenase
      activity in the pancreatic islet B-cell was recently proposed to represent a far
      from-uncommon contributing factor in the pathogenesis of non-insulin-dependent
      diabetes mellitus. In the present study, it was investigated whether the
      postulated genomic defect coincides with the biosynthesis of an enzymic protein
      with altered catalytic properties and might concern an isoenzyme distinct from
      that found in extrapancreatic tissues. The activity of FAD-linked
      glycerophosphate dehydrogenase, as measured by either a radioisotopic or
      colorimetric procedure, was indeed severely decreased in islets from rats
      injected with streptozotocin. The intrinsic properties of the enzyme were
      preserved, however, as judged from the affinity for L-glycerol-3-phosphate, the
      ratio in reaction velocity using either FAD or iodonitrotetrazolium as electron
      acceptor and the activation of the enzyme by Ca2+. When the same kinetic
      parameters were compared in islet, liver and spleen homogenates from normal rats,
      significant differences were observed, however, between these three tissues,
      suggesting the possible existence of distinct isoenzymes.

PMID- 1344999
TI  - Immunological and beta-cell-specific characteristics of diabetes-prone BB/OK rats
      and their congenic derivatives--a comparative study.
AB  - In a comparative study congenic rat strains bearing either the genetic background
      of diabetic BB/OK rats and the MHC (RTla) of diabetes-resistant LEW.1A rats
      (BB.1A/OK) or vice versa carrying the genetic background of LEW.1A rats in
      combination with the MHC (RTlu) of diabetic BB/OK rats (LEW.1BB/OK) and their
      parental rat strains BB/OK and LEW.1A were checked for insulin secretion of
      pancreatic islets, for the number of splenic and peripheral blood mononuclear
      cells (MNC) as well as for the mitogenic response of splenic MNC. Glucose
      stimulated insulin secretion of isolated islets of Langerhans was not different
      in 50, 70 and 100 day-old congenic rats and the progenitor rat strains excluding
      an impact of the genotype on this beta-cell-specific function. The number of
      splenic and peripheral blood MNC was reduced in BB/OK and BB.1A/OK rats compared
      to LEW.1A and LEW.1BB/OK rats. Splenic MNC from BB/OK and BB.1A/OK rats displayed
      a strongly decreased total [3H]thymidine incorporation under basal conditions as
      well as upon mitogenic stimulation by ConA in comparison with MNC from LEW.1A and
      LEW.1BB/OK rats. Thus, the occurrence of lymphopenia and the impairment of
      mononuclear cell proliferation in BB/OK rats is not related to the RTlu haplotype
      of the MHC but is linked to non-MHC genes as indicated by the phenotypic
      expression of these traits in congenic BB.1A/OK rats.

PMID- 1345000
TI  - Impact of dietary protein and fat source on the development of insulin-dependent
      diabetes in the BB rat.
AB  - Epidemiological studies show a remarkable geographical difference in the
      prevalence of IDDM, suggesting a role for environmental factors such as diet,
      infection, or stress in the etiology of the disease. Dietary modification has
      already been shown to be effective in the prevention of autoimmune diabetes in
      the BB rat and NOD mouse. We studied the effect of protein and fat source in the
      prophylaxis of diabetes in the BB rat. Natural ingredient rat chow was
      consistently associated with a high expression of the disease, whereas a casein
      based, defined diet significantly inhibited the development of diabetes.
      Substitution of casein with raw red lentils resulted in a markedly higher
      incidence. This is the first highly diabetogenic defined diet in the BB rat.
      Neither fish oil nor soy oil enhanced diabetes expression in the BB rat.
      Increased amounts of soy oil also did not influence the disease process. These
      results suggest a central role for dietary protein source in the pathogenesis of
      BB rat diabetes. We speculate that plant proteins containing anti-nutrients such
      as chemicals, lectins, enzyme inhibitors, and nonphysiologic amino acids may
      initiate or hasten the pathogenesis process via beta cell stress or immune
      response activation.

PMID- 1345001
TI  - Aminoguanidine inhibits the modification of proteins by lipid peroxidation
      derived aldehydes: a possible antiatherogenic agent.
AB  - The reaction of protein amino groups with lipid-peroxidation-derived aldehydes
      (LPDA) has been shown to play a key role in various pathological processes.
      Especially important is the reaction of LPDA with apolipoprotein B during
      oxidative modification of low density lipoprotein (LDL), which leads to its
      enhanced uptake by macrophages and, eventually, to atherogenesis. Since
      aminoguanidine, a drug which inhibits the advanced steps of glycation (probably
      by trapping reactive sugar-derived aldehydes), has been proposed as a therapeutic
      agent for the prevention of late diabetic complications, we have tested its
      ability to interfere with the modification of proteins by LPDA. LDL was incubated
      with cupric ions. Aminoguanidine at 5, 10 and 25 mM inhibited both the increase
      in electrophoretic mobility of LDL and the generation of thiobarbituric acid
      reactive substances (TBARS) (P < 0.001). It also inhibited the increase in
      electrophoretic mobility and 260-400 nm absorbance of bovine serum albumin
      incubated with malondialdehyde. These results suggest that aminoguanidine may
      have an antiatherogenic effect.

PMID- 1345002
TI  - Basal intermediary metabolism in impaired glucose tolerance and morbid obesity.
AB  - The effects of impaired glucose tolerance and obesity, in isolation and in
      combination, on basal (postabsorptive) intermediary metabolism were examined in
      four groups of subjects (n = 10 for each) matched for age and gender: Group 1:
      Non-obese healthy controls with normal glucose tolerance (75 g); Group 2: Non
      obese subjects with impaired glucose tolerance; Group 3: Morbidly obese subjects
      with normal glucose tolerance; Group 4: Morbidly obese subjects with impaired
      glucose tolerance. While there was no significant difference in fasting blood
      glucose concentrations between the four groups plasma immuno-reactive insulin
      concentrations were elevated (p < 0.01 or less) in the obese subjects relative to
      the non-obese subjects within each category of glucose tolerance. Basal
      immunoreactive insulin concentrations in non-obese subjects with impaired glucose
      tolerance were also elevated (p < 0.01) relative to the non-obese healthy
      controls. Concentrations of glycerol (p < 0.01), non-esterified fatty acids (p <
      0.01), and total ketone bodies (p < 0.001) were significantly higher in the
      obese/normal glucose tolerance and obese/impaired glucose tolerance groups
      relative to their matched non-obese counterparts. Compared with the subjects with
      normal glucose tolerance, only lactate (p < 0.05) and pyruvate (p < 0.05)
      concentrations were elevated in the non-obese/impaired glucose tolerance and
      obese/impaired glucose tolerance groups, respectively. In conclusion, in addition
      to fasting hyperinsulinaemia the regulation of lipolysis and ketone body
      metabolism is abnormal in the basal state in morbid obesity. By contrast, despite
      normal fasting blood glucose concentrations, impaired glucose tolerance is
      associated with disturbances of other aspects of basal carbohydrate metabolism.

PMID- 1345003
TI  - Monoclonal antibodies raised against semi-purified preparations of human islets
      define subpopulations of pancreatic cells.
AB  - Monoclonal antibodies were produced from fusions between splenocytes from BALB/c
      mice immunised with purified human islets and the mouse myeloma cell line NS
      0/Uncl. Supernatants from uncloned hybrids were screened by immunohistology on
      frozen sections of human pancreas. The range of specificities appeared to reflect
      the relative purity of the human islet preparations used. Eight monoclonal
      antibodies were investigated further, four of these bound to islet cells, two to
      acinar cells, one to ductal cells and one to occasional cells. The antigens
      recognised by these antibodies were characterised by immunohistology using a
      number of different tissues, as well as haemagglutination, immunoblotting and
      radioimmunoassay for insulin. Seven of the eight antibodies studied were IgM. One
      acinar cell antibody (IgG2a) precipitated proteins of 200Kd and 11OKd molecular
      weight. None of the antibodies bound directly to insulin. Seven of the antibodies
      appear to have defined previously unreported epitopes in the pancreas and will
      prove useful in further studies of human pancreatic cells.

PMID- 1345004
TI  - A new animal model of non-insulin-dependent diabetes mellitus induced by the
      NDK25 variant of encephalomyocarditis virus.
AB  - Intraperitoneal inoculation with NDK25, a variant of Encephalomyocarditis (EMC)
      virus which has been newly cloned from the M variant of EMC virus (EMC-M), caused
      DBA/2 mice to develop noninsulin-dependent diabetes mellitus. The NDK25-infected
      mice demonstrated abnormal glucose tolerance from 1 to 3 weeks after inoculation.
      The infection resulted in mild insulitis and the destruction of pancreatic beta
      cells at 1 week after inoculation and led to a significant reduction in the
      insulin content of the pancreas, but there was no ketonuria. The insulin content
      of the pancreas was recovered considerably from 15 +/- 3 at 1 week to 95 +/- 16
      micrograms/g pancreas at 12 weeks, although the latter value was still
      significantly lower than that of the control mice (P < 0.05). Under microscopy,
      mild and partial infiltration of mononuclear cells was observed in about half the
      pancreatic islets only 1 week after inoculation, and then disappeared. Thus, we
      believe we have established a new model of noninsulin-dependent diabetes mellitus
      using the NDK25 variant of EMC virus.

PMID- 1345005
TI  - Plasma alanine and lactate concentrations following glucose ingestion in normal
      and NIDDM subjects.
AB  - Conflicting evidence has been reported on the metabolic fate of glucose following
      oral ingestion. We measured the metabolic pattern of gluconeogenic substrates as
      alanine, predominantly produced by muscle, and lactate after an oral glucose load
      in ten normal subjects and in eighteen non-insulin dependent diabetes mellitus
      (NIDDM) subjects. Neither in normal or NIDDM subjects were significant increases
      in plasma alanine observed, whereas a significant increase in plasma lactate was
      observed at 60, 90 and 120 min after a glucose load. Although a similar behaviour
      in plasma alanine and lactate between normal and NIDDM subjects was found, in
      NIDDM significantly higher levels of plasma alanine and lactate were found at
      each time. From these observations we conclude: 1) when glucose is ingested under
      post-absorptive conditions, since plasma alanine levels do not change
      concurrently with lactate increase, muscle tissue does not play a predominant
      role in glucose disposal 2) after an oral glucose load, the pattern of
      gluconeogenic precursors (alanine and lactate) is similar in normal and NIDDM
      subjects 3) the main cause of fasting and post-prandial hyperglycemia in NIDDM
      subjects may be due to an overproduction of alanine as well as lactate.

PMID- 1345006
TI  - Serum lipoprotein Lp(a) in obesity.
AB  - Lipoprotein(a) [Lp(a)] has been added to the list of independent risk factors for
      cardiovascular disease (CVD), whose incidence is greater in obese subjects. There
      are few data available on the serum Lp(a) concentrations in obese individuals
      with or without insulin dependent diabetes mellitus (NIDDM). We selected 31 obese
      men with normal glucose tolerance (NGT) tests, 15 obese diabetic men, 14 non
      obese diabetic men and 17 healthy men as controls. We measured serum total
      cholesterol, HDL cholesterol, triglycerides, glucose, insulin and Lp(a). The mean
      Lp(a) levels in NGT obese men were 70.00 +/- 13.40 mg/l, which were similar to
      those found in normal controls (75.98 +/- 24.70 mg/l); significantly higher mean
      Lp(a) levels were found in obese diabetic men (168.84 +/- 56.43 mg/l) and in non
      obese diabetic men (240.85 +/- 63.35 mg/l). No significant correlation between
      Lp(a) levels and age, body mass index (BMI), total cholesterol, HDL cholesterol,
      triglycerides, insulin, was found; only a significant positive correlation
      between Lp(a) levels and glucose could be revealed (P < 0.05). Since higher
      levels of Lp(a) were found in NIDDM subjects with or without obesity, we conclude
      that hyperglycemia may influence the levels of serum Lp(a) facilitating its
      glycosylation in the liver with the consequence of a decline in its catabolic
      rate.

PMID- 1345007
TI  - Amelioration of dermal lesions in streptozotocin-induced diabetic rats by
      aminoguanidine.
AB  - As aminoguanidine (AG) is known to prevent non-enzymatic glycosylation in various
      tissues, we have histologically and biochemically evaluated AG effects on the
      skin in control, SZ-diabetic and AG-treated (25 mg/kgbw/day, 10w) diabetic rats.
      HbA1c and plasma glucose levels in diabetic and AG-treated diabetic rats were
      maintained about two times higher than those in control rats during the 10 weeks
      of the experiment. Histological findings revealed that the dermis in diabetic
      rats was thin and edematous, associated with swelling and degeneration of
      collagen fibers. Necrobiotic changes were seen in the lower dermis. These changes
      were greatly improved in AG-treated diabetic rats. Skin glucose contents in
      diabetic and AG-treated diabetic rats were about 10 times higher than those in
      the controls, whereas there was no difference in the sorbitol contents between
      three groups. Dry weight of the skin and collagen content was well correlated (r
      = 0.9044) and collagen represented 78.0 +/- 2.3% of the dry weight. By SDS-PAGE
      analysis of cyanogen bromide digests it was shown that high molecular weight
      peptides were increased in diabetic rats, but were decreased in AG-treated
      diabetic rats. The mean of glycosaminoglycan (GAG) contents of diabetic skin was
      54% of that in the controls (1.58 +/- 0.09 vs. 2.94 +/- 0.39 micrograms/mg dry
      weight, P < 0.0025), which increased significantly in AG-treated diabetic rats
      (1.75 +/- 0.07 microgram/mg dry weight, P < 0.01 vs. diabetic).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1345008
TI  - Detection of antibodies against both isoforms of glutamate decarboxylase in BB/OK
      rats by western blotting and immuno trapping enzyme activity assay.
AB  - The GABA-producing enzyme glutamate decarboxylase (GAD) is a prominent
      autoantigen in insulin-dependent diabetes mellitus (IDDM). Autoantibodies against
      GAD were found with a high prevalence in IDDM patients and in animal models for
      IDDM. The aim of this study was to detect autoantibodies against both isoforms of
      GAD in diabetic and non-diabetic but diabetes-prone BB/OK rats by Western
      blotting and to test their specificity to GAD by an immuno-trapping enzyme
      activity assay. Eighteen diabetic and 18 non-diabetic BB/OK rats (age 121 +/- 20
      days) were investigated. In 10/18 (56%) of the diabetic and 13/18 (72%) of the
      non-diabetic BB/OK rats autoantibodies against at least one GAD-isoform were
      detected by Western blotting. In the immunotrapping enzyme activity assay, the
      mean value of the diabetic (1151 +/- 552 cpm, n = 11) and nondiabetic BB/OK rats
      (1978 +/- 1213 cpm, n = 10) was significantly (p < 0.01) increased compared to
      the LEW. 1A control rats (581 +/- 274 cpm, n = 12). 7/10 (70%) individual sera of
      the non-diabetic and 5/11 (45%) of the diabetic BB/OK rats were positive in this
      test. In conclusion, the prevalence of GAD autoantibodies in BB/OK rat is
      connected with the genetic susceptibility to IDDM but is not a predictor for the
      onset of the disease in BB/OK rats.

PMID- 1345009
TI  - [Determinism and indeterminism in the study of risk factors for disease].
AB  - In epidemiology "risk" is stated as a probability. This statement implies
      adopting a definite position regarding the concept of probability in science:
      whether it has to be intended as a lack of knowledge or a casual component of
      biological phenomena. On this fundamental premise the authors discuss the
      epidemiological implications on the issue of "determinism" of the recent
      developments of chemical, physical and biological sciences, particularly the
      quantum mechanics and the theories of complexity. The authors suggest three major
      interpretations of the relationship between risk factors and disease: strong
      determinism, weak determinism and dualism determinism/indeterminism. For each one
      of these positions they discuss the consistency, affinity and implications on
      epidemiological work.

PMID- 1345010
TI  - [Development of an integrated system of family medicine--pathologic anatomy
      service to start epidemiologic studies on tumors occurring in an area of southern
      Italy. First results].
AB  - In Italy there are eight tumor Population-Based Registries (PBRs) that publish
      incidence data, and only one of them (Ragusa) provides data for Southern Italy.
      Usually, PBRs are based on data collection from Pathologists and medical records.
      Our integrated system differentiates from traditional PBRs because the
      information comes from the General Practitioners (GPs) and is completed with the
      diagnosis provided by the Pathologists (Ps). During two years we have registered
      1,057 new cancers on a middle period population of 212,644. GPs and Ps signed 395
      and 879 incident cases, respectively. GPs alone provided 16.8%, Ps alone 62.6%,
      and either source 20.6% of total cases. After excluding non melanotic skin
      cancers and bladder carcinoma, the GPs-Ps integrated system counted 828 new cases
      in two years. These incidence data are the first in our region (Puglia). The 178
      cases signed by GPs alone should have been lost if the informations of our PBR
      had been based only on local Ps' records. Moreover, 94 of GPs cases (11% of total
      cancers registered) were subjects who moved outside the area for diagnosis and
      treatment. Even if this article evaluates the effect of under-registration
      attributable to Ps or GPs, the cancer incidence data and the active involvement
      of GPs indicate that they could be usefully involved in the registration of
      cancer data.

PMID- 1345011
TI  - [Anti-rubella vaccine coverage in women 11-28 years of age: data on 5 local socio
      health units of Veneto].
AB  - Selective rubella vaccination in the 11 years old girls, has been carried out in
      the Regione Veneto (Venetian Land) since 1974. The rubella immunization rate in
      teh women born between 1962 and 1978, in five sanitary districts, is 68.25%; the
      trend of increasing vaccination is continuing. Important differences in the
      organization of vaccination campaign were found among the five districts.

PMID- 1345012
TI  - [Colorectal adenocarcinoma in patients with familial anamnesis positive for
      malignant neoplasms of the large intestine].
AB  - Familial aggregation of colorectal cancer occurs also among sporadic cases that
      are not part of defined genetic syndromes. First degree relatives of patients
      with "sporadic" colorectal cancer have a 3-4 fold increased risk of the same
      cancer. The aim of the present study is to investigate the relationship between a
      first degree family history of colorectal cancer and pathological and clinical
      features of the tumor (site, Dukes' stage, age at diagnosis, sex and survival of
      patients). 461 patients with colorectal cancer were evaluated (250 males and 211
      females) after obtaining informations about their family history of cancer. 52
      (11.25%) of them reported to have at least one close relative affected by
      intestinal cancer. Sex, age and stage of the disease are the only parameters that
      significantly affect survival. No relationship between family history of
      colorectal cancer and prognostic variables was observed.

PMID- 1345013
TI  - [Analysis of the quality of death certificates for neoplasms in the province of
      Ragusa].
AB  - The reliability of the death certificates issued in Ragusa for 379 of the 909
      cancer patients registered in 1986 by the Ragusa Cancer Registry, who had died
      within 31 october 1988, was investigated. Data were available for 365 cases
      deceased. A consistent proportion (32.8%) of disagreements between diagnosis of
      the Registry and cause of death reported on death certificate was observed,
      concerning errors of the second and third digit of ICD-9 (21.9%) and for lack of
      mention of cancer in the death certificate. The main causes of the loss of
      information were the issuing of the certificate by a M.D. of the permanent
      medical ward and not by the family doctor, and the lack of the document released
      by the hospital upon discharge of the patient, usually containing indication on
      diagnosis and treatment.

PMID- 1345014
TI  - [Mortality and care level of very low birth weight newborn infants. A population
      study].
AB  - A population study on 314 very low birth weight infants (VLBW) was carried out in
      1987 in the Lazio Region of Italy to investigate the relation between the
      availability at birth of neonatal intensive care and infant mortality. Fifty-two
      percent of VLBW infants did not survive the first year of life. The mortality
      Odds Ratios, adjusted for four potential confounding variables, did not show a
      beneficial effect of Maternity units with neonatal intensive care (level 3)
      compared with those with special (level 2) and normal care (level 1). The overall
      high crude mortality rate together with the homogeneity of odds ratios among the
      different levels of care suggest that, when a regionalized perinatal care system
      is missing, as in Lazio region, the availability of neonatal intensive care, per
      se, does not improve the survival on this group of infants.

PMID- 1345015
TI  - [Diffusion of smoking habit in the commune of Florence in 1989].
AB  - The results of a study on smoking habits of Florence inhabitants (14 years of age
      or more) are reported. A random sample of general population of the town (1744
      males and 1977 females) was recruited throughout the registration office and
      interviewed by mail or telephone. General compliance was approximately 85%.
      Thirty-seven percent of males and 25% of females were current cigarette smokers,
      29% of males and 11% of females were ex smokers. Males were heavier smokers both
      as concerns duration of the habit and daily amount of cigarettes. In males born
      after 1930 the smoking prevalence decreased gradually by period of birth, while
      it increased in females born before 1960. As a result the smoking habits of
      younger cohorts were similar in males and in females. In each sex age-adjusted
      smoking prevalence showed important differences by educational groups and in
      respect to national averages.

PMID- 1345016
TI  - [XIII oration. 1711].

PMID- 1345017
TI  - [Health services related migrations and information sources: the experience of
      the tumor registry of Ragusa].

PMID- 1345018
TI  - [What are tumor registries useful for?].

PMID- 1345019
TI  - [Contribution of general medicine physicians to the epidemiology of tumors.
      Italian Association of Epidemiology and referral Group on Tumor Registries of the
      Italian Law for the campaign against tumors].

PMID- 1345020
TI  - Postmarketing surveillance-one of the key issues in drug development.
AB  - The terms "postmarketing surveillance" or "human phase IV studies" are applied to
      all those examinations which are performed with a drug following its
      registration. The principles, methods of these examinations are discussed on the
      basis of international experiences. The authors also give some examples from
      Hungarian practice referring to this subject. They consider postmarketing
      examinations to be as important as the clinical pharmacological examinations
      preceding the introduction of a drug. The usefulness, role of a drug in the
      therapy may be definitely determined on the basis of the results of these
      studies.

PMID- 1345022
TI  - Local antiphlogistic treatment with Apulein cream.
AB  - The effectivity of two topical steroids, Apulein cream and Hydrocortisone
      ointment, was compared in women suffering from vulvitis and other superficial
      inflammations. The basic properties of budesonide and data from references have
      been discussed. In the examined cases Apulein cream proved to be a more effective
      and more rapidly acting antiphlogistic as compared to Hydrocortisone ointment.
      The adjuvant and symptomatic role of corticosteroid therapy and the importance of
      adequate target-specific treatment in cases of infection is emphasized.

PMID- 1345021
TI  - Hormone therapy in breast cancer.
AB  - Means and the currently accepted principles of hormone therapy of breast cancer
      have been summarized on the basis of data from references. Fields of application
      and adverse effects of anti-oestrogens, aromatase inhibitors, gestagens,
      gonadotrophin-releasing, and androgenic hormones have been analysed. Drugs with
      various mechanisms of action and available in Hungary have been discussed.

PMID- 1345023
TI  - Use of Dormicum sleeping pills in everyday practice.
AB  - Dormicum is a rapidly absorbed up-to date hypnotic of 3-4 hours' duration of
      action physiologically influencing the phases of normal sleep. In the course of
      the examination of 26 patients, 21 found the hypnotic action of 7.5-mg or 15-mg
      Dormicum doses to be highly effective. The drug proved to be an effective
      hypnotic also in the group of patients above 60 years of age (14). It is of
      special importance in the everyday practice of a general practitioner that the
      intake of Dormicum in the evening did not influence the physical and mental
      activity of the patients the next day.

PMID- 1345024
TI  - Evaluation of the antiemetic effect of domperidon in patients treated with
      cytostatic drugs.
AB  - Forty patients with various neoplastic syndromes received domperidon as a drug
      reducing nausea and vomiting. The drug prevents in the daily dose of 30 mg
      completely the occurrence of nausea and vomiting in 30% of the patients and in
      58% considerably reduces their intensity. The dose of 60 mg abolishes nausea and
      vomiting in 60% of the patients and alleviates in 35%. The drug had been
      administered through the whole period of chemotherapy without any side effects
      which may be attributed to its antagonist action to dopamine.

PMID- 1345025
TI  - Clinical examination of nitroglycerin spray (EGIS) in angina pectoris patients.
AB  - On the basis of our examinations it may be stated that the new product of EGIS
      Pharmaceuticals Nitromint aerosol seems to be effective and well tolerable in the
      course of clinical examinations. The drug action develops significantly more
      rapidly as compared to Nitromint tablet. Significant difference was not found
      when comparing the duration of action of the two products. The adverse effects
      are the same as the undesired effects of other short-acting nitrate preparations.
      Mostly local unwanted effects were observed. It can be recommended in all forms
      of angina pectoris for controlling pain syndrome and in effort angina for
      prophylactic purposes. In acute left heart failure it may be used in urgent
      cases. Because of its effectiveness and easy applicability the patients prefer
      Nitromint aerosol to Nitromint tablet.

PMID- 1345026
TI  - Clinical observations with Paxirasol aerosol in patients suffering from chronic
      bronchitis accompanying silicosis.
AB  - Paxirasol aerosol applied in daily 3 x 5 puff doses in the treatment of silicosis
      patients is found to be a well tolerated drug form. In the course of the 21-day
      therapy especially coughing and chest pain were moderated, but the product also
      controlled, the catarrhal coat formation on the mucosa. It influenced abundant
      expectoration and dispnoea beneficially. During the therapy the laboratory
      parameters did not change. The objective respiratory parameters improved but the
      change was non-significant. Paxirasol aerosol is found useful in the treatment of
      chronic bronchitis accompanying silicosis. Evaluable side-effects were not
      registered.

PMID- 1345027
TI  - The relation between atypical migraine and multiphasic oral contraceptives.
AB  - Data in references referring to the relation between atypical or menstrual
      migraine and the use of oral contraception have been reviewed. The authors own
      observations are discussed on this subject. Motilium and Voltaren have been
      successfully used for controlling vascular headache developing as a side-effect
      of contraceptive tablets. In case of migraine associated with dysmenorrhoea
      and/or premenstrual tension the management with triphasic hormone proved to be of
      therapeutic value. The authors call attention to the concurrent high incidence of
      these latter symptoms and suggest the further analysis of this problem. They
      collect evidence regarding that in the major part of cases atypical migraine is
      hormone dependent.

PMID- 1345028
TI  - Use of Klion suspension in paediatry and gynaecology.
AB  - Klion suspension was given to 42 girl and woman patients suffering from vaginal
      trichomoniasis. Negativity for Trichomonas was recorded in 73.8% of the cases in
      response to the first 10-day cure, and in 90.5% of the patients following
      repeated cures. The therapy had no notable side-effects. The liquid form of the
      medicine proved to be advantageous especially in the treatment of young girls but
      the possibility to take the drug diluted in soft drinks also facilitated the
      treatment of the partner.

PMID- 1345029
TI  - Leukotriene B4 and peptido-leukotriene levels during radiographic contrast media
      infusion.
AB  - The pathogenic mechanisms of radiographic contrast media (CM) reactions are still
      not well understood. Recently it has been proposed that leukotrienes (LT) may be
      involved in CM reactions. We measured plasma LTB4 and peptido-LT levels in 20
      subjects undergoing urography with 2 low osmolality CM (ioxaglate and iopamidol)
      in order to elucidate if CM infusion determines LT release in plasma. LTB4 and
      peptido-LT did not change significantly during infusion of the 2 CM. Blood
      pressure, heart rate, and the number of circulating granulocytes were not
      affected by CM infusions, further evidence that LT release did not occur. We
      conclude therefore that LT are not released during infusion with the CM studied.

PMID- 1345030
TI  - Fixed dose combination short course chemotherapy in the treatment of pulmonary
      tuberculosis.
AB  - In this study two highly effective chemotherapeutic regimens of 6 and 8 months
      duration were studied and compared with the standard 12 month therapy under full
      supervision at the National TB Centre and St. Peter's TB Hospital in Addis Abeba.
      Patients with direct smear positive pulmonary tuberculosis were admitted to
      hospital during the initial phase of treatment for two months. At two months,
      sputum conversion rates, by direct smear and culture respectively, were 82% and
      80% on Rifater, and 86 or 88% and 86% on the regimens containing separate
      preparations of isoniazid rifampicin and pyrazinamide, compared to 60% and 30% on
      the standard regimen. It was concluded that short course regimens of six or eight
      months with drugs either in combined form or separate preparations are more
      effective than the standard regimen.

PMID- 1345031
TI  - Why are agonadal and post-amenorrhoeic women so fertile after oocyte donation?

PMID- 1345032
TI  - Dual publication of abstracts.

PMID- 1345033
TI  - [Duodeno-biliary reflux during T-tube drainage: a clinical study].
AB  - The relationship between duodeno-biliary reflux and bile bacterial contamination
      was studied in 28 consecutive cases of T-tube drainage after cholecystectomy and
      choledochotomy. Patients were randomly divided into two groups of 14 each. Group
      I treated with positive pressure drainage (PPD), with the pressure in T-tube 0.3
      0.5 kPa higher than that created by sphincter resistance. Group II treated with
      traditional negative pressure drainage (NPD). It was found that the amount of
      duodenal reflux in group II was obviously larger than that in group I. We
      conclude that the traditional T-tube drainage incurs inevitably contamination of
      bacteria to bile by way of duodenal reflux. It is the consequence of bile flow
      dynamic disorder. PPD raises the bypass outflow resistance against the duodenal
      reflux and is thus superior to NPD.

PMID- 1345034
TI  - Effect of acupuncture on gastric acid secretion in healthy male volunteers.
AB  - Six randomized, placebo controlled studies were performed to investigate the
      effect of electroacupuncture on gastric acid output in 38 healthy males.
      Electroacupuncture decreased basal acid output when compared to placebo
      acupuncture [from 3.50 +/- 0.59 mmol/hr to 2.54 +/- 0.56 mmol/hr (P < 0.05)] as
      well as sham feeding-stimulated acid output [from 18.52 +/- 2.25 mmol/hr to 5.38
      +/- 2.11 mmol/hr (P < 0.005)], but had no effect on the pentagastrin stimulated
      acid output. The inhibitory effect of acupuncture on sham feeding-stimulated acid
      output was not affected by local anesthesia of the acupoint, but was prevented by
      a prior intravenous naloxone injection. Acupuncture did not alter plasma gastrin
      levels (20.7 +/- 7.6 micrograms/liter, vs control 21.2 +/- 7.2 micrograms/liter)
      but naloxone increased it (26.1 +/- 14.5 micrograms/liter) (P < 0.05). We
      conclude that the antisecretory effects of electroacupuncture do not result from
      decreased gastrin release or decreased parietal cell sensitivity to gastrin, but
      are mediated through naloxone-sensitive opioid neural pathways and vagal efferent
      pathways.

PMID- 1345035
TI  - Calcium supplementation prevents hypertensive disorders of pregnancy.
AB  - Preeclampsia, a hypertensive disorder of pregnancy, is a major cause of fetal and
      maternal morbidity and mortality. Epidemiologic studies have shown an inverse
      relationship between dietary calcium intake and gestational hypertension. A
      recent large-scale, randomized, double-blind, placebo-controlled clinical trial
      has shown that supplementation of pregnant women with 2 g calcium per day from
      the twentieth week of gestation to term can significantly lower the incidence of
      hypertensive disorders of pregnancy. The beneficial effect of calcium
      supplementation was apparent as early as the twenty-eighth week of gestation. The
      mechanism responsible for the effects of calcium on gestational hypertension is
      unknown.

PMID- 1345037
TI  - Valproic acid-induced placental and teratogenic effects in rats.
AB  - Studies on teratogenicity and pathology of the cenceptus were conducted in
      Sprague-Dawley rats treated with 600, 800, and 1,000 mg/kg valproic acid po on
      day 13 of pregnancy. Each of the three doses was maternotoxic and caused (1)
      resorptions and/or abortions, reduction in the number of live fetuses per litter
      and mean fetal weight, and defects of the tail, rib and phalanx; and (2)
      degenerative changes in the labyrinth (thrombosis, angiectasis in the maternal
      lacunar network, necrosis of cytotrophoblasts and suppressed proliferation of
      fetal capillaries), reduced diameter nearing obliteration of umbilical vessels,
      with or without karyorrhexis of embryonic tissues. The lesions in the placental
      labyrinth were specific but, in the embryonic tissues, they were generalized. It
      was postulated that the vascular lesions in the labyrinth and umbilicus may have
      influenced embryonic development by reducing maternoembryonic gaseous and
      nutritional exchange.

PMID- 1345036
TI  - Segmental absence of small intestinal musculature.
AB  - Three instances of segmental absence of small intestinal musculature are
      described. Based on their clinical and pathological features and on the 12 cases
      previously described in the English literature, these can be classified into two
      groups: primary and secondary. In the primary group, the etiology is unknown, the
      onset of symptoms is acute, and there are no pathologic findings in the remaining
      layers of the small bowel except for superimposed perforation, or
      intussusception. In the secondary group, there is a longer history of intestinal
      symptoms and of multiple surgical procedures. Histologically, there may be
      ischemic necrosis of remaining layers, fibrosis, calcification, chronic
      inflammation, and presence of macrophages. These findings indicate secondary
      destruction of muscle layers due to ischemia and/or infarction, interruption of
      the blood supply, or trauma.

PMID- 1345039
TI  - Precision of biological standardization of allergenic preparations.
AB  - Biological standardization (BS) aims at equilibration of the activity of allergen
      preparations from different types of allergen source materials. The biological
      unit (BU), proposed in the Nordic guidelines for 20 patients, has been found
      reproducible among different countries in Europe, but to be relatively imprecise,
      with a 95% confidence interval of about one power of 10. A more precise estimate
      of the biological activity of allergens or difference in sensitivity between
      populations would be of value. We used Ch, i.e. the concentration of allergen
      eliciting a wheal of the same size as histamine in the individual patient,
      estimated by regression line analysis. The Ch of 36 patients included in a BS
      trial was used. One of the 36 Ch-values was drawn randomly, and then sent back to
      the sample. This procedure was repeated 10, 20, 30, 40 and 60 times to create
      "samples" of different sizes. Ten samples of each size were produced. With 60
      "individuals", the 95% confidence interval of the sample and the confidence
      interval of the medians were reduced to less than a factor of 2, i.e. to 74 to
      128% of the median of the medians.

PMID- 1345038
TI  - Plasma lipid concentrations in hyperlipidemic patients consuming a high-fat diet
      supplemented with pyruvate for 6 wk.
AB  - We evaluated the effects of a three-carbon compound, pyruvate, on plasma lipid
      concentrations in hyperlipidemic patients consuming a high-cholesterol (560-620
      mg), high-fat (45-47% of energy; 18-20% of energy as saturated fatty acid),
      anabolic diet (0.11-0.12 MJ/kg body wt) for 6 wk. Forty subjects consumed the
      diet, randomly supplemented with 36-53 g pyruvate (n = 19) or 21-37 g polyglucose
      (placebo, Polycose, n = 21) as a portion of carbohydrate energy. Plasma
      cholesterol and LDL-cholesterol concentrations were unchanged in the placebo
      group, but decreased by 4% and 5%, respectively, in the pyruvate group (P < 0.05
      vs placebo). Plasma HDL-cholesterol, HDL3-cholesterol, and triglyceride
      concentrations were similar in both groups. Resting heart rate, diastolic blood
      pressure, and rate-pressure product were unchanged after 6 wk of therapy in the
      placebo group, but decreased by 9%, 6%, and 12%, respectively with pyruvate
      supplementation (P < 0.05 vs placebo). We conclude that pyruvate supplementation
      of a high-fat, high-cholesterol, anabolic diet will decrease plasma cholesterol
      and LDL-cholesterol concentrations without affecting the HDL-cholesterol
      concentration.

PMID- 1345040
TI  - Reducing distress associated with pelvic examinations: a replication.
AB  - A previous study of the effect of a new examination gown on patients' experienced
      discomfort during pelvic examination demonstrated that the gown was effective.
      This study replicated the previous study with a younger group of subjects. It was
      hypothesized that the new gown would reduce reported distress. Subjects were 147
      patients at a university student health center. Age ranged from 18 to 31.
      Informed consent was obtained and patients were randomly assigned to either the
      experimental gown or the standard drape condition. Following examination,
      subjects completed questionnaires assessing demographic characteristics, state
      and trait anxiety, desired changes in pelvic examination procedures, and
      reactions to the examination. The attending nurse recorded blood pressure.
      Results supported the hypotheses. Experimental subjects rated the gown as more
      comfortable than control subjects rated the drape. Results indicate that this
      simple stimulus control intervention reduces one source of distress associated
      with pelvic examinations.

PMID- 1345041
TI  - Three-year occlusal wear of posterior composite restorations.
AB  - The specific aims of this study were to: 1) measure the occlusal wear of four
      different dental composite materials placed in the posterior teeth of adults; and
      2) evaluate the effect of the clinical parameters, cavity class and tooth type on
      occlusal wear. Four different visible light-cured composite materials were used
      to make the restorations in this study. The restorations placed for this
      randomized clinical trial were scored through the use of an indirect evaluation
      system (M-L scale). The total sample size per recall ranged from 90 to 142
      restorations from baseline to 36 months. The mean wear at 36 months for
      Heliomolar, J&J Experimental (Adaptic II) and P-30 was 45-54 microns, which is
      rather low compared to the recently reported wear of other composite materials.
      Marathon exhibited significantly greater wear with a mean of 174 microns at 36
      months. The data also showed that cavity class and tooth type had no significant
      effect on the occlusal wear of the restorations made with the three low wear-rate
      materials, while restorations composed of the high wear-rate material exhibited
      more wear in molars than premolars; this effect was again not statistically
      significant. These data support the hypothesis that the overall wear of a
      composite restoration is more dependent on the material's properties than
      clinical parameters such as cavity class and tooth type.

PMID- 1345042
TI  - Recent papers related to oral oncology.

PMID- 1345043
TI  - Muirhead's syndrome--a syndrome of medullipin dependent hypotension.

PMID- 1345044
TI  - An alternate road.

PMID- 1345045
TI  - Nitric oxide (NO) in the cardiovascular system. Some physiological and
      evolutionary aspects.

PMID- 1345046
TI  - Persistent hypotension associated with hypermedullipinemia: a new syndrome.
AB  - A new syndrome is described in a patient with advanced renal insufficiency. This
      consists of severe and persistent hypotension causing weakness but associated
      with a clear mental status. Also present is evidence for decreased vascular
      reactivity. The hypotension was not orthostatic. The hypotension was associated
      with a circulating vasodepressor substance having the characteristics of
      medullipin 1. The medullipin appears to have been derived from the remaining
      right kidney. Hypotension existed despite the presence of major prohypertensive
      mechanisms, including an endstage kidney, hyperreninemia and hyperaldosteronemia.
      It is likely that hypotension due to hypermedullipinemia is an entity occurring
      in the human being.

PMID- 1345047
TI  - Fibrosis of the human heart and systemic organs in adrenal adenoma.
AB  - In experimental animals, chronic mineralocorticoid (MC) excess is associated with
      fibrosis of the myocardium and systemic organs, where both a reactive, i.e.
      interstitial and perivascular, and reparative, i.e. microscopic scarring
      following cardiac myocyte necrosis, fibrosis are found. We sought to determine if
      a similar fibrous tissue response was present in human myocardium and systemic
      organs in association with adrenal adenoma. Postmortem specimens of heart,
      adrenals, pancreas, lungs, kidney and liver were obtained from 5 patients (age 67
      +/- 5 years) with autopsy-proven adrenal adenoma. Documented histologically
      normal tissue from age-matched patients was used for comparison. Tissue sections
      were stained with the collagen specific stain Sirius Red F3BA and analyzed using
      normal and polarized light. Reactive and/or reparative fibrosis was found in the
      heart, pancreas, adrenal glands and lungs, but not in the kidney or liver. These
      observations support a link between chronic MC excess and fibrosis of the heart
      and systemic organs in humans with adrenal adenoma.

PMID- 1345048
TI  - Plasma atrial natriuretic peptide (ANP) concentration in patients with
      pheochromocytoma.
AB  - The interaction between catecholamines (CA) and ANP is not clearly established.
      The effects of excess endogenous CA on ANP secretion can be investigated in
      patients with pheochromocytoma. We studied 27 patients with surgically and
      histologically proven pheochromocytoma (P) aged 19-70 years. In 16 of these
      patients plasma ANP study was repeated after surgical removal of the tumour. The
      control group (C) consisted of 20 healthy volunteers aged 21-48 years. Moreover,
      42 patients with uncomplicated mild to moderate essential hypertension (EH) aged
      18-48 years were also studied. In P higher plasma ANP concentration versus C, EH
      was found (51.9 +/- 8.1; 25.5 +/- 1.5; 19.3 +/- 1.5 fmol/ml, respectively). In 16
      patients with P, increased plasma ANP level (mean 63.3 +/- 12.6 fmol/ml) declined
      after surgical removal of the tumour (mean 22.4 +/- 2.9 fmol/ml). In the P
      patients no relationship was found between plasma ANP and hormonal patterns of
      the tumour or between plasma ANP and plasma catecholamines, whereas significant
      positive correlations between plasma ANP and both systolic and diastolic blood
      pressure and heart rate were demonstrated. These results suggest that excess CA
      produced by the chromaffin tumour induce ANP secretion via stimulation of
      adrenergic receptors. However, influence of the haemodynamic changes evoked by CA
      cannot be excluded. It is suggested that increased secretion of ANP may be of
      some importance in maintaining blood pressure homeostasis in patients with
      pheochromocytoma.

PMID- 1345049
TI  - Effect of ketoprofen on blood pressure, endocrine and renal responses to chronic
      dosing with captopril in patients with essential hypertension.
AB  - The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the blood
      pressure and renal function of essential hypertensive patients depend on the
      specific type of NSAID and antihypertensive drug administered. Twelve patients
      with essential hypertension, aged 35 to 59 years, stabilized (blood pressure less
      than 140/90 mmHg) with captopril, received ketoprofen (100 mg bid for 7 days) or
      matching placebo in a randomized double-blind cross-over fashion. A 3-week wash
      out period was included between treatment periods. Blood pressure on the first
      and last days of the placebo treatment period (137 +/- 7 (SD)/80 +/- 8 and 139 +/
      11/81 +/- 9 mmHg) was similar to respective values during ketoprofen therapy
      (136 +/- 10/79 +/- 7 and 143 +/- 10/81 +/- 9 mmHg). The mean differences in
      systolic and diastolic blood pressures, at the end of the treatment periods,
      between ketoprofen and placebo were 4 (95% confidence intervals -5, +13) and 0 (
      8, +8) mmHg, respectively. Ketoprofen had no effect on 24-h urinary sodium
      excretion (160 +/- 33 and 147 +/- 39 mmol/24 h for ketoprofen and placebo,
      respectively). Ketoprofen was without effect on glomerular filtration rate, renal
      plasma flow and filtration fraction. In conclusion, our data suggest that
      ketoprofen is a safe choice when short-term treatment with a NSAID is indicated
      in an essential hypertensive patient treated with a converting enzyme inhibitor
      such as captopril.

PMID- 1345050
TI  - The stroke preventive effect in elderly hypertensives cannot fully be explained
      by the reduction in office blood pressure--insights from the Swedish Trial in Old
      Patients with Hypertension (STOP-Hypertension).
AB  - OBJECTIVE: To study whether the cardiovascular preventive effect of
      antihypertensive therapy can be explained solely by the reduction in office blood
      pressure, and to what extent the risk of stroke and cardiac events is associated
      with in-study diastolic blood pressure (DBP) and systolic blood pressure (SBP).
      DESIGN: The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension)
      was a prospective, randomized, double-blind, multicentre trial comparing active
      antihypertensive treatment with placebo in patients aged 70-84 years. The study
      group comprised 1,627 elderly patients (mean blood pressure 195/102 mm Hg; mean
      age 75.7, SD 3.7; 63% females). The average follow-up was 25 months (range 6-65
      months). No patient was lost to follow-up. METHOD: We applied a Poisson model
      taking current age, sex, treatment, DBP and SBP into account for all patients in
      the study. The constants of the model were estimated by the maximum likelihood
      method. RESULTS: The risk of stroke was significantly lower (42%, p = 0.0402) for
      a patient on active therapy than for a patient on placebo having the same blood
      pressure level, age, and sex. There was a corresponding, non-significant,
      reduction in cardiac events of 21%. In the whole study group the risk of stroke
      increased by 3% per mmHg (p = 0.0247) with increasing diastolic blood pressure
      for a given systolic pressure. The corresponding value for cardiac events was 2%
      per mmHg (p = 0.0376). CONCLUSION: In STOP-Hypertension we found a substantial
      risk reduction in stroke in actively treated patients, which was not solely
      explained by the blood pressure reduction obtained by treatment with beta
      blockers and a potassium-sparing diuretic combination.

PMID- 1345051
TI  - Influence of early antihypertensive treatment on vascular and cardiac design in
      SHR with and without renal hypertension.
AB  - The present study was designed to explore to what extent pressure reduction by
      antihypertensive therapy and pressure elevation by renal hypertension are able to
      affect structural vascular and cardiac changes in young spontaneously
      hypertensive rats (SHR). Pressure elevation in SHR was induced by means of
      superimposing 2 kidney, 1 clip renal hypertension (2K1C). Pressure reduction was
      achieved by means of the vasoselective calcium antagonist felodipine from 6 to 13
      weeks of age in both clipped and unclipped SHR. Vascular structure of the
      skeletal muscle was assessed hemodynamically by perfusing a hindlimb preparation
      and left ventricular dimensions were calculated from pressure-volume
      relationships of isolated hearts arrested in diastole. Induction of renal
      hypertension in SHR resulted, besides augmentation of arterial pressure in a
      marked concentric left ventricular hypertrophy, i.e. elevations of wall thickness
      to internal radius ratio. Likewise, in renal hypertensive SHR, a structural
      adaptation of the skeletal muscle vascular bed occurred, reflected as elevations
      of minimal vascular resistance and maximal generated perfusion pressure.
      Antihypertensive treatment for 8 weeks with felodipine reduced and also prevented
      mean arterial pressure from increasing further in SHR, and in SHR with
      superimposed renal hypertension by approximately 15% (p < 0.001 for both). In
      renal hypertensive SHR, felodipine partly prevented the development of
      exaggerated structural changes, both in the heart and in the skeletal muscle
      vascular bed, as reflected by reduced wall thickness to internal radius ratio and
      reduced minimal vascular resistance by 22% and maximal pressure response by 10%
      respectively (p < 0.01 for both parameters).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345052
TI  - Radioimmunoassay of endothelin in human plasma.
AB  - A specific and sensitive radioimmunoassay (RIA) for determination of endothelin-1
      (ET-1) in human plasma has been developed. Antibodies were raised in rabbits
      using synthetic ET-1 conjugated to thyroglobulin as immunogen. The antibodies
      obtained were used at a final dilution of 1:300,000 yielding maximum binding of
      61.7 +/- 3.0% (mean +/- 1 SD, n = 20) of 125I-ET-1. The ID50 (inhibitory dose
      50%) was 4.5 +/- 0.6 fmol/100 microliters (mean +/- 1 SD, n = 20). The
      sensitivity of the RIA was 0.33 fmol/100 microliters standard solution. No cross
      reactivity was observed with endothelin-3, big-endothelin-1, atrial natriuretic
      factor, angiotensin I or angiotensin II. The cross-reactivity with endothelin-2
      was 100%. Endothelin was extracted from acidified plasma with Sep-pak C18
      cartridges and recovery of ET-1 added to normal plasma was 70.9 +/- 10.3% (mean
      +/- 1 SD, n = 12). The concentration of ET-1 in plasma from normal subjects was
      1.5 +/- 0.4 pmol/l (mean +/- 1 SD, n = 11) ranging from 1.0 to 2.2 pmol/1.
      Extracts of normal human plasma subjected to high performance liquid
      chromatography on a reverse phase C18 column showed one peak of immunoreactivity
      co-eluting with the standard for ET-1. From these data it is concluded that the
      immunoreactive material measured in normal plasma with the present RIA is
      identical to ET-1.

PMID- 1345054
TI  - The Epilepsy Europe meeting. Glasgow, Scotland, 1-5 September 1992. Abstracts.

PMID- 1345053
TI  - Aortic compliance in hypertension--effects of cilazapril and hydrochlorothiazide
      can be distinguished.

PMID- 1345055
TI  - [Diagnostic strategies in cholestatic jaundice].

PMID- 1345056
TI  - [The significance of lobular inflammation in chronic active hepatitis].
AB  - Authors have performed an anatomo-clinico-biological comparison of two groups of
      hepatitis with lobular inflammation: group I with a simple lobular inflammation,
      called lobular hepatitis, and group II with a lobular inflammation associated
      with portal and periportal hepatitis, called chronic active hepatitis (CHA) with
      lobular hepatitis. Furthermore, a comparative study of these forms with a group
      of CHA without lobular inflammation was performed. Both forms of lobular
      inflammation appeared in young patients, the large majority of whom were infected
      with the hepatitis B virus; in 5 cases of CHA with lobular hepatitis the presence
      of the delta agent in the liver, possibly responsible of the lobular
      inflammation, was detected. The two forms of lobular hepatitis are differentiated
      by: the fivefold increase of ALAT over the normal value, with usually normal
      gamma-globulins and albumin, in the first group; in the lobular hepatitis, HBsAg
      was present in 33% of cases in the first group and in none of the patients of the
      second group, suggesting the integration of HBsAg within the hepatocytic genome;
      the clinical picture was generally asymptomatic in the first group and noisier,
      with hepatomegaly, in the second group; the period elapsed since the acute
      hepatitis was shorter in the first group (4-11 months) in 8 of 15 patients and
      longer in the second group. The clinical course of these forms of hepatitis if
      unforeseeable and the diagnosis is established on the basis of the morphological
      examination.

PMID- 1345057
TI  - [Current problems in the diagnosis of biliary lithiasis].

PMID- 1345058
TI  - [The biochemical profile of the cholestatic syndrome].

PMID- 1345059
TI  - [The etiological diagnosis of the painful foot].

PMID- 1345060
TI  - [Reiter's syndrome (a clinical study)].

PMID- 1345061
TI  - [An association between ankylosing spondylitis and rheumatoid polyarthritis;
      comments on 3 cases].
AB  - The article is an analysis of 3 clinical cases, characterized by the presence of
      the lumbosacral axial involvement, with the radiological evidence of a bilateral
      sacroiliitis and a peripheral polyarthritis displaying a rheumatoid picture, with
      rheumatoid factors in the serum and in 2 of the cases also in the articular
      fluid. These cases belong to the HLA-27 B histocompatibility type, a feature
      which could be, according also to the data of literature, an explanation of the
      association of these two diseases.

PMID- 1345062
TI  - [Lethal midline granuloma in Senegal. (Apropos of 15 cases)].
AB  - African authors, other than senegalese, have not paid enough attention to lethal
      granuloma, a terrible disease. This series is about a series collected between
      1975 and 1990. It is particularly high compared to other series in the world. If
      diagnosis is easy for the clinician, much care must surround the pathological
      answer. Those diagnosis problems and difficulties of treatment (represented by 11
      deaths) are studied.

PMID- 1345063
TI  - [Fungi in the hospital environment and infectious risk].
AB  - Using petridishes at hospital in services with risk patients, we have isolated
      Aspergillus (41.5%), Penicillium (26.4%), Candida (12.2%), Fusarium (7.5%),
      Mucorales (5%), Scopulariopsis (5%), Scytalidium (0.8%), Tricothecium (0.8%),
      Ulocladium (0.8%). Several fungi grew at 37 degrees. These saprophytic fungi
      could give opportunistic mycoses in immunodeficient patients.

PMID- 1345064
TI  - [Non-infectious complications of treatment of hydrocephalus by shunt].
AB  - From january 1975 to december 1988, 234 hydrocephalus cases of newborn and infant
      treated by ventriculo-peritoneal or ventriculo atrial shunt have been studied at
      Dakar CHU (University Teaching Hospital) neuro-surgery clinic. The non infectious
      complications of this type of surgical treatment using inert material, have been
      observed in 52 patients or 22 per cent even though infectious complications can
      be noted in 34 per cent of the cases. Among these non infectious complications
      the extra-cranial mechanical are the most frequent. Fistula or subcutaneous
      collection of CSF (13 cases), cutaneous necrosis (12 cases), shunt material
      disconnection (9 cases), obstruction (8 cases). Chronic subdural hematoma has
      been proved rare and cranio-stenosis secondary to drainage, exceptional. The
      treatment of mechanical complications by simple revision emphasizes the
      maintenance of shunt material in place contrary to the treatment of infectious
      complications that occurs almost always the removal of a material already
      expensive associated with a long standing antibiotic chemotherapy. Successive
      revisions and reinsertion of material can raise technical difficulties which will
      lead to delayed infection. Careful technical procedure of shunting constitutes
      the best mean prevention against these non infectious complications.

PMID- 1345065
TI  - [Aerobic capacity training in heterozygote sickle cell athletes].
AB  - Two sport groups, all training physical educational and sports teachers at the
      H.N.I.P.S.S. of Dakar have been tested by measure of maximum consumption of
      oxygen (VO2max) before and after a three month aerobic training. The first group
      contained 10 abnormal hemoglobin (AS) subjects. The second group 11 normal
      hemoglobin (AA) subjects. The results do not show any difference in the reaction
      of adaptation between the two groups.

PMID- 1345066
TI  - [Antithrombin ii in eclampsia: estimation of predictive value].
AB  - We have observed in our study that antithrombin III activity decreases very
      significatively in eclampsia (p < 0.0001). A level of 90% was defined as a
      threshold. All the rates which are under or equal to 90% have 78.3% as a positive
      predictive value and those over 90% have a 98.7% as a negative predictive value
      for the overcoming of eclampsia. We have concluded that the 90% antithrombin III
      activity represents the alarm level for over coming eclamptic crises. The
      determination of the antithrombin III activity must be systematically done in
      every hypertensive pregnancy with proteinuria.

PMID- 1345068
TI  - [Diagnosis and follow up of the development of a large left intraventricular
      thrombus. Apropos of 1 privileged case].
AB  - The authors report a rare observation of left intraventricular thrombus in a 39
      years old senegalese man with a dilated non-obstructive cardiomyopathy. With the
      echocardiographic follow-up, it was possible to follow the regression of the
      clot. Echocardiographic diagnosis and evolutive problems of such left
      intraventricular thrombus are reviewed.

PMID- 1345067
TI  - [Dispersion of biochemical analysis results in Dakar: preliminary results].
AB  - Now and then, the conflicting character of results of some analyses is
      prejudicial to patients (financial and particullary psychological repercussions),
      to the laboratories (renown) and to the practitioners (difficulties of
      interpreting). After a study of the dispersion of some analyses results, the
      authors propose a creation of an Interlaboratory Quality Control in Clinical
      Biochemistry in Senegal.

PMID- 1345070
TI  - [Rational prescription if protein evaluation in the diagnosis and follow up of
      protein-energy malnutrition].
AB  - In our countries, a good prescription of analysis would help to reduce hospital
      costs without modifying the efficiency of the diagnosis approach. In this work,
      the authors establish a bond between medicos and biologists by a good indication
      of protein check-up in the diagnosis and follow up of protein-energy malnutrition
      (PEM). After a discriminant analysis of all the results of protein check-up, two
      groups of markers are individualized depending on whether the PEM is accompanied
      or not by inflammatory complications. Finally, they recommend a systematic
      prescription of the useful group in case of inflammation associated with PEM,
      because infectious and parasitic diseases are almost constant among our
      malnourished infants.

PMID- 1345069
TI  - [Effect of water fasting on sport performances in the laboratory].
AB  - 15 sport men heart rate and central temperature were measured at rest and at the
      end of a progressive maximal exercise. Maximum consumption of oxygen (VO2 max)
      was estimated after the effort. The experience began in the morning from 9 to 11
      a.m. and the afternoon from 4 to 6 p.m. In the first time subjects had a normal
      alimentation and in the second they observed a rigorous fast. The comparison of
      the results doesn't show difference induced by fast on VO2 max and maximal heart
      rate. However heart rate at rest and capacity of work decrease during fast and
      permit to think that a more intensive and long exercise in more strenuous
      climates than this one should give significative modifications.

PMID- 1345071
TI  - [Preparation and characterization of a monoclonal antibody directed against
      bovine leukocytes].
AB  - A monoclonal antibody (MAb-M25) was obtained by immunizing BALB/C mice with
      tumour cells isoled from a familial thymic lymphosarcoma observed in Friesian
      cattle. The specificity of this MAb was assessed using PBL, lymphoids organs
      (lymph node, spleen, tonsil, Pleyer's patch) and non lymphoid tissues (liver,
      skin) from clinical normal cattle. Immunofluorescence and immunohistochemistry
      methods were used to characterise this monoclonal antibody. It reacted with 27%
      of peripheral blood lymphocytes and a large proportion of mononuclear cell in the
      lymphoid organ, in the thymic cortical, in the dermis and in the liver. It also
      stained lymphocytes of the mantle of follicules and thymocytes of the thymus
      cortex. The tissue distribution of M25 have a similarity with the human CD1c Mab
      and the bovine 20-27 MAb.

PMID- 1345072
TI  - [Scurvy].

PMID- 1345074
TI  - [Sacro-ilial tuberculosis (sacrococcygeal). Apropos of 1 case].
AB  - In a single case review the authors recapitulate the different methods for the
      presentation of sacro-ilial infectious and underscore imagery techniques which
      are of prime importance in diagnostic work. X-rays can only reveal advanced sacro
      ilial bone joint lesions which are under-evaluated. In the absence of HI-Tech
      imagery, surgical biopsy must be widely recommended to identify the germ and
      allow early diagnosis.

PMID- 1345073
TI  - [Christopherson's tumor. Review of the literature apropos of a retroperitoneal
      localization].
AB  - Alveolar soft-part sarcoma is rare, and its retroperitoneal localization in psoas
      major muscle, exceptional. Concerning a case occurred in a young woman, the
      authors focus on the characters of this tumor of unknown histogenesis which
      affects predominantly young adults, mainly females. This disease, which
      symptomatology is poor and which evolution is particularly long for such a
      neoplasm, leads inexorably to death despite surgical treatment that represents to
      date, the unique efficient therapeutic modality.

PMID- 1345075
TI  - [Problems linked to trismus in a dental office].
AB  - The objective of this report was to know the most frequent etiology of trismus we
      meet in our dental office as well as the different treatment set up. The question
      is an observation of 58 cases of trismus that we received in two different dental
      clinics: Odontology and Stomatology Institute and Social Hygen Institute of
      Dakar. The results we got show that trismus is an odontologist's daily problem.
      Although its treatment is relatively easy, it is good to remember that etiologies
      other than dental exist.

PMID- 1345076
TI  - [Anatomic study of the anterior interventricular artery (Ramus interventricularis
      anterior). Apropos of 200 anatomical samples].
AB  - The coronary system has been studied on the basis of 200 hearts taken during
      necropsies and treated by injection of a synthetic resin followed by corrosion.
      Sixty samples were used for the study of the L.A.D. and one hundred and fifty
      were used for studying intercoronary anastomosis on L.A.D. The study highlighted
      the following particularities: the left coronary is the most common origin of
      L.A.D. (90 per cent cases); the L.A.D. irrigates: all the left ventricle ventral
      wall, the right apical part of both ventricles and the upper portion of the
      interventricular septum; out of 92 anastomoses, 49 were located on the L.A.D.
      which could protect against ischemia.

PMID- 1345077
TI  - [Drug prescription in Dakar and outskirts].
AB  - Drugs are very important to human life due to their human mission and to the
      essential role they play in modern society through their real social function.
      When used in certain conditions, drugs are expensive, ineffective and can even
      become dangerous and the source of poisoning with serious consequences. In order
      to minimize risks and accidents, special attention is paid to drugs from their
      conception to their elimination by the body, resulting inter alia in a severe
      control of their prescription. In Dakar, where are can find the greatest number
      of prescribers in Senegal, this control is rarely respected. This situation can
      be fraught with serious consequences for the health of populations.

PMID- 1345079
TI  - [Bacteria associated with diarrheic episodes in young camels in Niger].
AB  - During diarrhoeic episodes of young camels in Niger, bacteria such as Salmonella
      enteritidis, E. Coli, Staphylococcus sp., Clostridium perfringens and other
      bacteria were isolated from stool samples. Bacteria roll in this pathology is
      discussed, and a treatment is proposed, compared with antibiogram results.

PMID- 1345078
TI  - [Biological diagnosis of hepatitis e. Completion of a test for detection of
      infected patients].
AB  - The aim of this study is to set up a biological method for diagnosing hepatitis E
      using an immunoenzymatic technique. This technic attaches specific IgM of a
      monkey experimentally infected with the Hepatitis E virus to a solid phase. These
      antibodies capture the HEV antigen (AgHEV) present in the stools of patients with
      hepatitis E. Antigen was then revealed using purified and labelled IgG from the
      same monkey. Using this method, we were able to: prove the existence of sporadic
      cases of hepatitis E in Dakar, biologically confirm the diagnosis of hepatitis E
      in 53.33% of patients suffering from hepatitis during an epidemic in Constantine
      and in 26.3% of patients in Bangkok who contracted oral-fecal transmitted
      hepatitis. Confirmation by inhibition and control reactions demonstrated the
      specificity of this test and its usefulness as a tool for the biological
      diagnosis of hepatitis E.

PMID- 1345080
TI  - [Hypertrophic pyloric stenosis of the infant. Apropos of 8 cases].
AB  - Eight cases of Infantile Hypertrophic Pyloric Stenosis collected in 10 years
      (1980-1989) in the Pediatric Surgery Unit of the Surgical Clinic of Dakar are
      reported. The rarity of this pathology among Blacks and a male predominance are
      noted. The clinical onset occurred after an average period of 3,25 weeks marked
      by food vomiting. At the start of the surgical management the age of patients was
      6 weeks. X-ray examination following a barium meal showed no passage of contrast
      in 3 cases. However a narrowed and elongated pyloric canal was noted in 5 cases.
      Abdominal sonography was used in 3 cases and showed gastric stasis with a
      hypertrophy of pyloric muscle. A rammstedt pyloromyotomy was performed after a
      period of few hours to 13 days of resuscitation. A duodenal perforation
      complicated the operation twice and was subsequently repaired. In the post
      operative period, two patients died within 2-3 days. One of them had duodenal
      perforation. Six patients made a good recovery.

PMID- 1345081
TI  - [Evaluation of Vibrio cholerae isolation over 10 years in CHU Fann].
AB  - A retrospective study, concerning ten thousand five hundred and sixty five
      (10,565) stool samples examined from 1981 to 1990, was done at the Bacteriology
      Laboratory of Fann University Hospital, Dakar (Senegal). One thousand and six
      hundred and eighty (1680) enteropathogen agents were detected (15.9%), five
      hundred ninety two (592) of which were vibrio cholerae. The quasi totality
      strains of the vibrio cholerae (99.8%) belonged to the Ogawa serotype; they were
      isolated mainly during the hot and raining season. Young male adults were the
      most infected. Most of the strains revealed sensitive to Sulfamids and
      Tetracycline.

PMID- 1345082
TI  - [Mycetoma with neurological manifestations. Inherent therapeutic difficulties in
      these localizations. Apropos of 5 cases].
AB  - The authors report five cases of mycetomas with an original localization, cranio
      encephalic and vertebro medullary. Four times it concerned a dorsal or cervical
      mycetoma with deep enlargement responsible for compression of the spinal cord. In
      the 5th case, scalp infection reached the dura mater. All patients have got
      histopathological diagnosis. Therapeutic difficulties are evocated about these
      singular localizations in a pathology for which greater amputation stands as the
      rule.

PMID- 1345084
TI  - [Bacteriology of shigella isolated in a tropical zone CHU].
AB  - From 1981 to 1991, five hundred eighty one Shigella's strains were isolated in
      the Laboratories of the CHU Fann of Dakar. They represent 24.8 per cent of
      enteropathogen agents and 4.3 per cent of diarrhoeae causative agents. Shigella
      flexneri was predominant (71%), following by Shigella dysenteriae (14.5%),
      Shigella sonnei (11.4%) and Shigella boydii (2.5%). In pediatric hospital 90 per
      cent of strains were isolated between 1 and 5 years age; in adults, the pic was
      found from 20 to 30 years. Five of the 13 tested antibiotics had inhibited 89 to
      96 per cent of strains. The isolation of multiresistant strains will be in
      rapport with the antibiotic resistant plasmide portage.

PMID- 1345083
TI  - [Cylindroma of the epiglottis].
AB  - The observation of an exceptional laryngeal localization of an adenoid cystic
      carcinoma allows authors to review diagnostic, therapeutic and increasing
      problems of this glandular carcinoma. The reported case constitutes a histologic
      surprise. An economical removal has allowed to obtain a long remission without
      recurrence, nor metastasis; this never put back the principle of the broad
      surgery to institute when faced this type of cancer, but just emphasize the
      interest of an early treatment.

PMID- 1345085
TI  - [Ureteral-pelvic junction syndrome in the child. Apropos of 8 cases].
AB  - Eight cases of uretero-pelvic junction syndrom collected in the ten past years
      are reported. They are 4 males and 4 females ranged from 18 months to 15 years
      with a mean age of 4.5 years. This age too late is probably due to the
      misknowlege but also to the lack of information about the pathology. The main
      characteristics of this syndrome are analysed according to the literature. All
      patients except one underwent nephrectomy because the irreverible lesions of the
      kidney. The authors emphasize the importance of early diagnosis done by antenatal
      echography but it can be made with a good clinical examination followed by the
      results of I.V.P. It is necessary for them to make parents, general practitioners
      and paediatricians sensitive to that pathology to avoid such operating act whose
      consequence are very serious where as it is benign.

PMID- 1345087
TI  - [Spinal meningiomas. Apropos of 14 cases].
AB  - Fourteen cases of spinal meningiomas were reviewed. There were 5 males and 9
      females, with an average age of 40 years who underwent surgical treatment at the
      Neurosurgical Division of Dakar University Teaching Hospital. The thoracic spine
      was involved in 10 cases. The location of the tumor in the spinal canal was
      epidural in 6 cases and subdural in 8 cases. 7 patients (50%) had marked
      improvement or stabilization: 4 patients died and in 3 cases, a recurrence was
      noted. The authors emphasize diagnostic difficulties encountered in the epidural
      forms.

PMID- 1345086
TI  - [Surveillance of heavy metal pollution of mangrove oysters in Senegal].
AB  - Joal-Fadiouth, located in department of Mbour (region of Thies), 118 kilometers
      from Dakar, the capital of Senegal, is an area where one can find a large swamp
      with mangroves whose self-propagating roots serve as growth support for young
      oysters. The importance of those oysters, both on the domestic and foreign
      markets and the ever greater threat of pollution of our coasts led us to search
      for and measure out heavy metals. In fact, it is well know that the accumulation
      of those elements in the food chain can be at the origin of severe poisoning. It
      appears, in the light of the results obtained that the level of pollution by
      heavy metals in this part of the senegalese coast has not yet reached alarming
      limits.

PMID- 1345088
TI  - [Male sterility through hormonal insufficiency in Cameroon].
AB  - At the Gyneco-obstetric service of the Yaounde CHU, we have studied 361 cases of
      couple sterility. In 38%, the man was responsible. Among these patients, less
      than 50% had a complete hormonal checkup. The hormonal cause of sterility was
      confirmed in 63 patients by static tests using the radio-immunologic method.
      These hormonal abnormalities were most the result of a primary testicular
      insufficiency (23.8%) and seminifer tube abnormalities (38.5%).

PMID- 1345089
TI  - [Conjugal sterility at Dakar CHU: epidemiological profile and evaluation limits
      apropos of 429 cases].
AB  - The writers draw up the outcome of the medical management of infertiles couples
      at Dakar's teaching hospital over a period of 7 years (1983-1989). Restrictives
      factors (low rate incomes, social and psychological obstacles) make that medical
      management difficult. The responsibilities are shared among the couple with sex
      ratio of 1 man for 3 women. Among the women the etiologies dominated are the
      sterility of the Phaloppe tubes (81%) among men with the oligo and the azoospermy
      (32 and 27%). Sterility within married couples is a problem of public health that
      becomes more acute every day. A better handling of this problem through
      preventive medicine and elementary sanitary training is necessary.

PMID- 1345090
TI  - [Congenital cystic dilatation of the choledochus: apropos of a case diagnosed in
      an adult Senegalese women].
AB  - The authors report a case of congenital cystic dilatation of the choledochus
      diagnosed on a 37 years old senegalese woman. It is an uncommon affection in
      Africa. The clinical presentation with various signs is reviewed. Ultrasound or
      cholangiography confirms the diagnosis. Surgical excision of the cystic
      dilatation is the best treatment because of the high risk of cancerisation.

PMID- 1345091
TI  - [Seroprevalence of anti-Delta antibodies in hospital workers in Dakar].
AB  - 708 hospital workers in CHU of Dakar were tested to HBs antigen: among them 128
      were positive and tested to Delta antibody by ELISA Abbott kit. Seven men and one
      woman were positive; however the positivity to Delta antibody is neither linked
      to sex, nor to age. 87% of the Delta antibody carriers were found among the
      trainees, and 50% of them studied in the Odonto-Stomatology Institute.

PMID- 1345092
TI  - [Central temperature and its circadian rhythm in men acclimated to the
      intertropical zone].
AB  - The central temperature has been measured at rest over 623 black men who are
      between 18 and 78 years old, and perfectly fit to warm weather in the
      intertropical areas. The measures have been taken according to two protocols:
      dealing with the ambiant temperature and the humidity (ambiant temperature
      varying from 20 degrees C to 42 degrees C, the humidity from 70% to 80%). dealing
      with the daily cycle: The central temperature was recorded every 3 hours by 24
      hours at two different periods in the year, on June (the ambiant temperature
      varying from 28 degrees C to 42 degrees C and the humidity from 33 to 42%), and
      on December (the ambiant temperature varying from 21 degrees C to 25 degrees C
      and the humidity from 70 to 90%). On the one hand, the results showed an
      influence of the external temperatures on the circadian curves of the central
      temperature (maximal central temperature taken in the afternoon was 37.2 degrees
      C in winter and 37.6 degrees C in summer). On the other hand, there's a linear
      relation between central temperature and ambiant temperature, at least on certain
      limit and apart from the weather. In spite of two modifications, the
      thermoregulator system of some designed individual remain efficiency but would
      work rather than according to the mechanism of the "following" systems.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1345093
TI  - [Diagnosis of tuberculosis by specific DNA amplification directly in samples].
AB  - The polymerase chain reaction (PCR was used to identify M. tuberculosis in
      specimens from patients with suspected pulmonary tuberculosis. A segment of the
      IS 6110 sequence and of the Cro EL gene were amplified and identified by
      hybridization with specific probes labeled with peroxidase. The results are in
      agreement with those obtained using standard microbiological techniques or
      clinical criteria. The PCR method allowed the detection of M. tuberculosis in 22
      out of 58 samples that were acid fast staining negative. The number of patients
      with at least one positive sample by PCR was much higher in the group with
      suspicion of tuberculosis (14/28) than in the control group (3/23). This
      demonstrates the possibility of using PCR technology in endemic areas for
      tuberculosis.

PMID- 1345094
TI  - [The plague: disease and vaccine?].
AB  - Plague has existed in Madagascar since 1896, with epidemic control achieved by
      GIRARD with an EV vaccine in 1937. Plague persists in Madagascar, however, due to
      the large animal reservoir. With a predilection for nodal tissues, Yersinia
      pestis is a virulent bacteria that is potent inducer of antibody synthesis.
      Immunity mechanisms stimulated by infection were studied: 1. In human by
      immunoenzymatic methods 2. In mice by seroprotection and vaccinating tests.
      Induced immunity for people in endemic and endemic-epidemic areas, is
      significant, affecting approximately 70% of these populations. In non endemic
      areas, immunity is found in only 33% of the population, perhaps this explains the
      persistence of epidemic? In all cases, this immunity is a quick onset (6 days),
      is persistent (> 2 years), and has demonstrable serious recognition of YOP
      (Yersinia Outer Proteins) by Western Blot method. Human antibodies were shown to
      be protective for mice. Animals vaccinated by YOP were protected equally well,
      when compared to animals infected with Yersinia pestis and subsequently treated
      with antibiotics. Finally, YOP aerosols were also shown to induce antibodies. In
      conclusion, plague is a vaccinatable bacterial disease and YOP can be used as an
      animal vaccine to permit plague control in the rat reservoir.

PMID- 1345095
TI  - [Cysticercosis in Madagascar: diagnostic and therapeutic improvement].
AB  - Human cysticercosis is linked to infection by the larval stage of Taenia solium:
      Cysticercus cellulosae and was identified in Madagascar since 1901.
      Neurocysticercosis constitute, when parasite is localized in cerebral vesicles, a
      disease with important neurologic symptoms: epilepsia, spasms... This disease
      would be diagnosed before parasite calcification and this diagnosis permit
      Praziquantel treatment indication, with good results in many cases. We have
      developed cysticercosis diagnosis permitting: stage definition of the disease:
      Elisa and Western Blot tests, therapeutic following by enzyme immunoassay capture
      of serum cysticercosis antigens. We have observed: disease prevalence of 18%
      proving high rate of circulating parasite, in the countries studies,
      significative variation of circulating antigens and/or antibodies, one month
      after one or two Praziquantel treatment, in 82% of 130 patients. This disease
      seems to be important in Madagascar in neurologic syndromes, but the solution of
      this problem would result in prophylactic and concerted actions by public health
      means.

PMID- 1345096
TI  - [Epidemiology and prognosis of cervix cancer. Experience of the University
      Gynecology and Obstetric Clinic Ignace Deen of Conakry in 10 years: 1982-1991].
AB  - The cancer of the cervix is a tumor that can be detected at an early stage.
      Unfortunately, it is still detected lately in our service. Thus, it is the
      underlying cause of death by gynecological affection. After a preliminary work in
      1982 about 35 case histories, the authors undertake a 10 years retrospective
      study where they showed that: the cancer of the cervix is the primary
      gynecological cancer (78.7%), it obtains between 25 and 65 years, the most often
      associated factors are early sex, (28%), poor living conditions (22%),
      cercivitise (17%), metrorrhagias (24%) and leucorrhoea are the most frequent
      signs. buding lesions are the dominant macroscopic form (68%) epidermoid
      carcinoma is the most important histological type, 98.7% cancer cases are
      detected at advanced stages (T3 and T4), the prognosis is dramatic: most patients
      die at home. This is a great public health issue the solution of which implies
      the collective action of decision-markers, health personnel and the communities
      themselves in order to promote early detection.

PMID- 1345097
TI  - Renal transplantation in infants, a therapeutic option?
AB  - Renal transplantation is widely accepted as the treatment of choice for endstage
      renal failure in childhood. Since dialysis is regularly applied to infants with
      renal failure, the question logically arises, can infants also receive renal
      transplants and what are the outcomes? A review of the literature and the
      clinical experience at the University of Minnesota supports the performance of
      renal transplantation in infancy. Present patient and graft survival rates for
      infants are indistinguishable from those of older children. While living adult
      donors are preferred, adult cadaveric kidneys have also been successfully
      transplanted. Following successful transplantation, the infants have generally
      enjoyed "catch-up" growth and accelerated psychomotor development. While there
      may be problems related to fluid and electrolyte balance in these smallest
      patients, the majority of the problems encountered mirror those seen in any child
      undergoing transplantation. Renal transplantation is regularly successful in
      infancy and should be considered an integral component of the therapy for any
      child with chronic renal failure.

PMID- 1345098
TI  - Paediatric aspects of renal transplantation: experience of a single centre.
AB  - From 1970 to 1991 a total of 244 renal transplantations were performed in 203
      children at the Medical School in Hannover. The mean patient age was 10.4 years
      with a range between 11 months and 16.9 years. Fifty-nine children received a
      living donor graft from one parent and 144 received cadaveric grafts. Forty-two
      children were transplanted without prior dialysis treatment. After 20 years the
      overall survival rates were 86% for the patients and 39% for the first grafts.
      Grafts from donors below 5 years of age had a less favourable survival (44% after
      5 years). Pre-emptive transplantation yielded comparable results with the benefit
      of a shorter period of uraemia. Hypertension developed in 80% of transplanted
      patients. Only children with living related donor grafts had significantly less
      hypertensive problems independent of the immunosuppressive regimen. Post
      transplantational growth improved under cyclosporin. Children with nephropathic
      cystinosis also showed catch up growth after transplantation under cyclosporin.
      The long-term outcome and rehabilitation of grown-up recipients were encouraging.

PMID- 1345099
TI  - Update of pediatric liver transplantation.
AB  - Liver transplantation is an effective and widely accepted therapy for children
      with end-stage liver disease. Major indications include primary liver disease,
      resulting in hepatic insufficiency, or severe morbidity secondary to chronic non
      progressive liver disease and metabolic diseases of the liver. Liver replacement
      should not be considered if there is an acceptable alternative therapy. Relative
      contraindications to transplantation include irreversible impairment of other
      organ systems, major systemic infection and diseases expected to recur after
      transplantation. Early referral for pre-transplant evaluation is important to
      confirm the proper diagnosis and determine priority for transplantation, to
      identify potential contraindications, and to assist in supportive care of the
      patient with chronic liver disease. Innovations such as reduced-sized liver
      grafts and most recently, living related liver transplantation have increased the
      donor supply of organs for small infants and significantly reduced pre-transplant
      mortality. In addition, living donor transplantation allows infants to benefit
      from transplantation before developing severe complications of end-stage liver
      disease and reduces the incidence of primary graft non-function and rejection.
      Immunosuppression following transplantation is maintained with
      methylprednisolone, azathioprine and cyclosporine. Acute rejection is treated
      with short bursts of high-dose corticosteroids and when necessary OKT3. With this
      approach, 90% of the episodes of rejection can be successfully controlled.
      Survival after transplantation has steadily improved and survival rates of 70%
      90% are routine. Following transplantation, children experience rapid nutritional
      restoration, increased muscle strength, marked progress in gross motor
      development and improved general health.

PMID- 1345100
TI  - 20-year anniversary of Children's Hospital of the Medical School Hannover and
      paediatric transplantation.

PMID- 1345102
TI  - Pre- and post-transplant assessment of liver function in paediatric liver
      transplantation.
AB  - The pre-operative risk of paediatric liver transplantation candidates (n = 41)
      was assessed in a prospective study by means of clinical symptoms, conventional
      static and liver blood flow dependent dynamic liver function tests. Nine patients
      died during the 365-day waiting period. The data were subjected as covariates to
      a survival analysis in the Cox proportional hazards model. There was a
      significant relationship between the results of mono-ethylglycinexylidide (MEGX)
      formation and ICG test and the 365-day survival rate. In the stepwise analysis,
      none of the remaining parameters improved the predictive ability when added to
      the dynamic liver function test results. The assessment of post-transplantation
      liver function was studied in 27 patients during the first 28 postoperative-day
      period. In addition, liver function was studied in a cross-sectional study 1-7
      years after successful liver transplantation in children with complete or partial
      rehabilitation. In the early postoperative period severe organ damage was
      indicated by both static and dynamic liver function tests. In the later course
      after transplantation no deterioration of liver function measured with MEGX
      formation was to be observed. These findings demonstrate the usefulness of
      dynamic liver function tests in the pre- and post-transplant assessment of liver
      function.

PMID- 1345101
TI  - Orthotopic liver transplantation in liver-based metabolic disorders.
AB  - The efficacy of orthotopic liver transplantation (OLT) in the management of more
      common liver-based metabolic disorders associated with severe liver damage, alpha
      1-antitrypsin deficiency (PIZZ), Wilson disease and tyrosinaemia has been
      demonstrated and indications defined. An early mortality in excess of 15% and
      finite resources limit its use. Phenotypic heterogeneity make the precise
      indication in other disorders less certain. In disorders in which endstage liver
      disease is less frequent such as cystic fibrosis, haemochromatosis and
      galacosaemia it has been a very effective therapy. It has been used with
      encouraging results in disorders in which the liver is structurally normal such
      as Crigler-Najjar type I, primary hyperoxaluria type I and primary
      hypercholesterolaemia. In these it should be performed before there is permanent
      damage to brain, kidneys or heart. OLT in the short term prevents hyperammonaemic
      coma in urea cycle defects and may prevent extrahepatic disease in glycogen
      storage disease type IV. Its limitation in reversing all metabolic effects in
      these and other disorders is discussed. It is ineffective in protoporphyria or
      Niemann Pick disease type II (Sea Blue Histiocyte syndrome) in which the
      transplanted liver acquires the lesions of the initial disorder and extrahepatic
      features progress. Early referral provides optimum circumstances to assess the
      benefits of OLT as compared with those of other forms of management and to
      achieve transplantation at the ideal time. The place of OLT in management will
      require constant review as metabolic disorders are better defined, new forms of
      therapy evolve and as techniques of liver transplantation and modes of
      immunosuppression improve.

PMID- 1345103
TI  - Bone marrow transplants in genetic diseases.
AB  - The first paper [9] advocating the displacement use of bone marrow
      transplantation (DBMT) to treat a variety of genetic metabolic diseases
      (including thalassaemia major) was put before a European Working Party in 1978.
      It evolved from mainly Westminster experience which showed the need [6] for DBMT
      and first successfully used donors other than matched siblings [9]. The
      principles of using DBMT to install a donor marrow as a component factory which
      can last a lifetime are outlined. It is not a panacea, being applicable to only
      about 7% of known inborn errors. Worthwhile correction of some 50 previously
      disabling diseases in over 700 patients has already been achieved worldwide and
      for most of the survivors no further treatment is used after 1 year. Guidelines
      for future extension, including gene transplants, are offered. The superior
      results of elective DBMT (about 95%) should encourage paediatricians to aim for
      earlier diagnoses and evaluations for transplants.

PMID- 1345105
TI  - Heart-lung transplantation for cystic fibrosis.
AB  - Heart-lung transplantation for cystic fibrosis has become an established form of
      treatment over the last few years. This paper considers the assessment and
      preparation of patients, the surgical procedure, immunosuppression, post
      operative care and the results of surgery. The best survival rates to 1 year are
      70%-80% with possibly a less favourable survival for younger patients. Major
      problems include shortage of donor organs, post-operative management of patients
      with multisystem disease and obliterative bronchiolitis. The majority of
      patients, however, do well with a greatly improved quality of life and the medium
      term results are encouraging.

PMID- 1345104
TI  - Chemotherapy versus bone marrow transplantation in childhood acute lymphoblastic
      leukaemia. BFM Study Group.
AB  - Twenty-five years ago over 90% of children with acute lymphoblastic leukaemia
      (ALL) died of this disease. Dramatic improvement has been achieved since then by
      employing risk-adapted, aggressive polychemotherapy protocols. More than 90% of
      children with ALL treated according to, for example BFM-protocols, have nowadays
      cure rates in the range of 70%-80%. However, 10% of patients do not initially
      respond adequately to standard induction chemotherapy. They are characterized by
      distinct chromosomal abnormalities such as translocation (9; 22) or combinations
      of early treatment failure and other risk factors as cytogenetic abnormalities,
      lineage-specific surface markers or tumour load at diagnosis. In this group of
      patients in first complete remission and certainly in the vast majority of
      relapsed patients, allogeneic bone marrow transplantation (BMT) has evolved as an
      alternative approach allowing further intensification of myeloablation and the
      introduction of an additional antileukaemic alloreactivity. Nevertheless, the
      decision for a marrow transplant in children has to be made very carefully
      because of a significant increase in treatment related mortality and BMT-specific
      risks like acute and chronic graft-versus-host disease with a critical iatrogenic
      chronic morbidity. This is even more evident, if mismatched or unrelated
      transplants are being considered. The indications for one or the other treatment
      modality according to the current BFM strategy are discussed.

PMID- 1345107
TI  - Thoracic organ transplantation in the paediatric age group. The Hannover
      experience.
AB  - Growing experience in terms of immunosuppression, recipient and donor selection
      as well as organ preservation has established thoracic organ transplantation as a
      therapeutic option for many children with end-stage cardiopulmonary diseases.
      While dilated cardiomyopathy and isolated myocardial failure represent the main
      indications for cardiac transplantation, replacement of the lungs or heart and
      lungs is necessitated in cystic fibrosis, primary and secondary pulmonary
      hypertension as well as some types of complex congenital heart defects involving
      the pulmonary arteries. We have performed a total of 20 heart, 4 heart-lung, 2
      single lung and 1 double lung transplantation in the paediatric group up to 17
      years of age. While with respect to the limited experience worldwide, early
      mortality after lung and heart-lung transplantation is still high (50%), long
      term results in isolated cardiac transplantation using triple drug
      immunosuppression are excellent (79% survival after 6 years) without major
      impairment of renal function, arterial blood pressure, growth development and
      physical rehabilitation as well as social reintegration. Freedom from graft
      atherosclerosis of the allografted heart is documented over a 5 year follow up,
      while no data are available on the incidence of obliterative bronchiolitis after
      lung transplantation in the paediatric group. Despite only limited evidence of
      long-term dysfunction, diagnosis and prevention of chronic rejection should be
      given utmost attention to allow for a normal life span in this younger age group.

PMID- 1345106
TI  - Heart transplantation in children: mid-term results and quality of life.
AB  - From 1987 to 1991, heart transplantation was undertaken in 49 infants and
      children with either end-stage cardiomyopathies (28 patients) or severe
      congenital heart disease (21 patients including 16 having already been surgically
      but unsuccessfully treated). Their age ranged from 13 days to 15 years (mean =
      4.5 +/- 4.2 years; median = 2.5 years). There were 12 early and 7 late deaths
      (overall mortality = 38%), mainly due to graft dysfunction, acute or chronic
      rejection, and infectious complications, mostly viral. Optimal criteria in
      selecting both donors and recipients are crucial to reduce early mortality and
      should never be transgressed despite the critical shortage of organs. The
      actuarial probability of survival was 64% at 1 year and 57% at 5 years. Our 30
      mid-term survivors (62%) were submitted to a close follow up programme which
      includes endomyocardial biopsies, even in the very young, since non invasive
      criteria failed to mark every rejection episode. Maintenance therapy was always
      steroid-free to start with (cyclosporin+azathioprine) but in almost one half of
      our oldest survivors, it failed to avoid rejection and we had to add low-dose
      oral steroids for at least several months. Epstein-Barr virus related
      lymphoproliferations occurred in four patients, two of whom died and two
      recovered with specific therapy. Renal function was closely monitored: tubular
      and interstitial lesions were found on renal biopsies and were associated with
      moderate functional changes. The quality of life of the children who survived
      heart transplantation was considered as near normal in a little more than one
      half of the cases but many issues (late coronary disease, drug toxicity, long
      term compliance to follow up and therapy) remain significant concerns for the
      future.

PMID- 1345108
TI  - Age and the immune response in pediatric renal transplantation.
AB  - Because renal transplant outcome is poorer in young children when compared with
      older children or adults, it is reasonable to question whether immune reactivity
      relative to renal allograft rejection differs between young children and adults.
      While this hypothesis is far from established, preliminary data suggest that
      young children may represent an immunologically-defined subgroup distinct from
      adults and perhaps at high risk for renal allograft rejection. From a
      histocompatibility standpoint, infants may show some subtle differences in HLA
      typing results when compared with older children or adults. Children may also be
      at higher risk than adults for rejection when the transplant is performed in the
      presence of a historically positive, currently-negative lymphocytotoxicity
      crossmatch. Several non-specific tests of cellular immunity have been used to
      characterize the strong immunologic responder, i.e. the person who has an
      increase tendency to vigorously reject a renal allograft. Children in general and
      young children in particular may fall into this group. Children 5 years old and
      younger have significantly increased numbers of CD2+, CD3+, and CD4+ T
      lymphocytes when compared with older children. Young children also have higher
      than expected functional indices of cellular immune function. Taken together,
      these data suggest that children, and particularly young children, may have a
      heightened immunologic responsiveness, which may in turn represent an increased
      propensity for allograft rejection. Appropriate modification in immunosuppression
      may be indicated to optimize renal transplant outcome.

PMID- 1345110
TI  - Ethical and psychological aspects of living donorship and life with a donated
      organ.
AB  - There is far-reaching consent in the literature that public and consensual
      agreements on the basics of the different aspects of medical ethics are
      inalienable before the instigation of any innovative transplant procedure. In the
      case of a certain method and/or of an individual patient, however, the ultimate
      ethical evaluation can most likely never be entirely complete before this
      application. Ethical evaluation depends on the actual criteria used, the present
      knowledge regarding the risk--benefit--balance as well as on the ethical
      evaluation of the patient's and his family's own feelings and expectations which
      are not entirely conscious. In relation to the so-called "fundamental and
      constant ethical guidelines" and under a psychological perspective potential,
      ethical conflict constellations are presented which have to be dealt with in the
      process of ethical and psychological evaluation before living organ
      transplantation.

PMID- 1345109
TI  - The influence of long-term morbidity on health status and rehabilitation
      following paediatric organ transplantation.
AB  - Driven by the technological and immunological innovations of the past decade,
      paediatric transplantation has evolved quickly to occupy an important clinical
      role in the management of vital organ failure. With this success, the focus of
      clinical attention has moved progressively from an institutional to a more
      comprehensive community perspective, and the long-term success of transplantation
      has assumed greater importance in the evaluation of risk and benefit. Five-year
      patient survival now exceeds 90% after living donor or cadaveric renal
      transplantation, 70% following heart or liver transplantation, and approaches 60%
      at 2 years for the more developmental procedures of heart/lung and lung
      transplantation. Successful transplantation is accompanied by compelling evidence
      of improved quality of life. The earliest and most prominent gain is in physical
      capability, with a progressive re-establishment of social and psychological
      functioning compared to age-appropriate developmental norms. More than 75% of
      long-term recipients are in school or employed with a high rating of life
      satisfaction. Rehabilitation is threatened, however, by the complications of long
      standing organ failure and long-term immunosuppression. These principally
      encompass skeletal and developmental disorders, metabolic abnormalities, cardio
      vascular disease, renal dysfunction, and chronic infection or malignancy arising
      as a result of impaired immune surveillance. Prevention or effective management
      of these debilitating sequelae is a principal goal in the changing paradigm of
      organ transplantation for the current decade.

PMID- 1345111
TI  - Transplantation--a new dimension for paediatrics.
AB  - Amazing advances have been achieved over the last 20 years in transplantation. As
      well as the problems of rejection and its control there are other difficulties
      which have to be confronted. There are shortages of donors, problems of selection
      for treatment and the problems of funding this expensive form of therapy. The
      need to make choices has to be considered and the criteria in determining choice
      have to be determined. Of particular concern in paediatrics are the problems that
      arise in relation to rehabilitation and the need to provide a multi-disciplinary
      approach to care. Finally, we have to remember that our enthusiasm for the
      possibilities of saving life and new treatments must not interfere with the basic
      responsibility to prevent suffering; at times the preservation of life at all
      costs is not justified, but in such circumstances doctors and other health care
      professionals have a responsibility for providing support both to the patient and
      to the family.

PMID- 1345113
TI  - Bactericidal activity of ciprofloxacin upon Escherichia coli and Acinetobacter
      baumanni.
AB  - The mechanisms of bactericidal activity of ciprofloxacin (mechanisms A and B)
      upon cells of a strain of Escherichia coli and one strain of Acinetobacter
      baumannii were investigated under different conditions. The killing of E. coli
      cells by ciprofloxacin was significantly reduced by chloramphenicol, but this
      antibiotic showed almost no activity upon killing of A. baumannii cells by this
      quinolone. Similar results were obtained when rifampicin was added to
      ciprofloxacin. Bactericidal activity of ciprofloxacin upon nondividing cells of
      E. coli was lower and that upon non-dividing cells of A. baumannii was not
      affected when compared with activity of ciprofloxacin upon dividing cells of both
      microorganisms. These results demonstrate that the antibacterial activity of
      ciprofloxacin upon A. baumannii is independent of protein and ARN synthesis, a
      fact which suggests that this quinolone exerts only bactericidal mechanism B upon
      A. baumannii. This finding might explain, at least in part, the lower
      susceptibility of this microorganism to ciprofloxacin.

PMID- 1345114
TI  - Biotyping of Serratia marcescens strains of clinical origin.
AB  - One hundred and ninety five Serratia marcescens strains of clinical origin
      isolated at the Children's Hospital of Mexico (Hospital Infantil de Mexico) in
      1978 and at the National Institute of Pediatrics (Instituto Nacional de
      Pediatria) in Mexico City in 1977 and from 1988 to 1989, were studied and
      compared. All strains were identified using the biotyping system described by
      Grimont and Grimont, without modification. The most numerous biogroup found was
      A5/8, and the frequencies of isolation of each biotype varied depending on the
      institution where it was isolated and the period of study.

PMID- 1345112
TI  - New immunosuppressive drugs: needs in and applications to pediatric
      transplantation.
AB  - The evolution of immunosuppressive therapy toward synergistic drug combinations
      seeks to minimize toxicity while potentiating efficacy. Median effect analysis
      discerns synergistic drug combinations that may be suitable for in vivo
      experiments in animals and for subsequent clinical trials. These studies suggest
      that two drugs rapamycin (RAPA) and brequinar (BQR) display synergistic effects
      in combination with cyclosporine. This combination must be evaluated for relative
      toxicity versus efficacy. Clinical trials to assess the individual toxicities of
      RAPA and BQR are presently underway in order to discern appropriate doses for
      randomized trials of clinical efficacy.

PMID- 1345115
TI  - [Biological features and experimental pathogenicity of Candida strains isolated
      by hemoculture at the Hospital Infantil de Mexico "Federico Gomez"].
AB  - In a period of 15 months (1990-1991) it was carried out 5781 blood cultures in
      which 180 strains of yeast-like were isolated. 116 of these strains were selected
      for biochemical classification, cellular and colonial morphology and experimental
      determination of virulence in mice. Most of the strains were classified as
      Candida albicans (60%) and the others were C. tropicalis (15.5%); C.
      guillermondii (10.3%); T. glabrata (6.8%); Rhodotorula rubra (3.4%); Cryptococcus
      neoformans (2.58%) y C. parapsilosis (0.86%). C. albicans ATCC14053, y C.
      tropicalis ATCC14056 and T. glabrata ATCC15545 were employed as controls. The
      virulence test was performed using mice of 20-30 gr (4-6 weeks age) by
      intravenous injection in caudal vein with 0.5 ml of different suspension from
      10(5) to 10(9) CFU/ml. Observation time was 10 days. Target organ was kidney by
      macro and microscopic observation of micro-abscess death. LD50 was estimated by
      the Reed-muench method. Intraspecific and interspecific differences were
      observed. It is more valid if we take into account that the experiment was done
      in homogenous population of host without risk factor which influences the human
      population in hospitals. Experimental virulence was compared with the evolution
      of diseases in the human host of which the strain was isolated.

PMID- 1345116
TI  - Antibody response to Babesia bigemina infection in calves measured by ELISA and
      immunoblotting techniques.
AB  - To measure the antibody response to Babesia bigemina with an ELISA test, three
      groups of cattle were experimentally infected with two isolates of the parasite.
      It was possible to demonstrate specific antibody binding directed against the
      parasite as early as the 7 days postinfection (PI). The highest level of antibody
      was obtained around day 1 to 23 and remained detectable for 260 days. Challenge
      of the animals 260 days PI with a tick-induced B. bigemina infection depicted
      that homologous strain-challenged calves did not show an increase of IgG antibody
      levels, where as those challenged with the heterologous isolate did. In the
      latter groups the resulting level of antibodies was even higher than after the
      primary infection. The immunoblotting technique showed that the antibody response
      is probably directed against groups of B. bigemina components with a relative
      mobilities of 68-64 kDa, 62-54 kDa and 52-42 kDa, which appear to be major
      components of the protozoa. By observing the cross-reacting antigenicity among
      seven B. bigemina isolates, it was demonstrated that these components are not
      isolate-restricted.

PMID- 1345117
TI  - [In vitro decrease of the cytolytic effect of E. histolytica by inhibition of its
      phosphofructokinase].
AB  - The C14 radioactive label of PPi analogues was incorporated to E. histolytica
      after 24 hours of incubation at 37 degrees C; more than 90% of trophozoites
      remained viable. The PPi dependent phosphofructokinase was isolated in order to
      determine its kinetic parameters. With PPi, the Km was 18.06 +/- 0.91 micromol/mL
      1. Using three different PPi analogues (tetrasodium salts) of (I) 1,1 hydroxy
      methyl diphosphonate; (II) 1,1 hydroxy ethylene diphosphonate; (III) 1,1 hydroxy
      nonano diphosphonate, KiI was 35.19 +/- 1.74; KiII was 42.65 +/- 0.65, and KiIII
      2as 62.81 +/- 0.27 micromol/mL-1. The graphic expression of these results shows
      that the enzyme was competitively inhibited by the three analogues. When
      trophozoites were incubated with each one of the three inhibitors, a correlation
      was observed between the concentration and the cytolytic inhibition with an r =
      0.98. Nevertheless, the slope obtained was different for each one of them. The
      smallest concentration of inhibitor to achieve a 50% lysis inhibition of
      trophozoites was that of inhibitor III. In addition, it was demonstrated that the
      incubation of the trophozoites with this inhibitor increased the time needed to
      destroy CHO cells. We conclude that enzymatic inhibition of the PPi dependent
      phosphofructokinase caused by the PPi analogues was responsible for the
      modification of the lytic capacity of trophozoites, possibly by altering the
      metabolic pathway of carbohydrates.

PMID- 1345118
TI  - [Entomology of onchocercosis in Soconusco, Chiapas. 6. Quantitative studies of
      the transmission of Onchocerca volvulus by 3 species of Simuliidae in a community
      with high endemicity].
AB  - In Guatemala, there is no doubt about the participation of Simulium ochraceum as
      vector of Onchocerciasis. However, in Mexico practically there are not studies
      focussed to determine the role of this species in the transmission. The objective
      of the present investigation was to determine which of the 3 species of Simulium
      founded in the Soconusco region of Chiapas, is the main, and which were secondary
      in the transmission of Onchocerciasis in that area. The locality of Morelos, in
      the Huixtla "municipio" of Chiapas, localized a 1200 meters over the sea level
      (mosl) were selected to carried out the present study. According to own
      parasitological studies, this locality is considered as highly endemic (more than
      66% prevalence). From March 1979 to March, 1981, we performed captures of
      Simulium sp caught on human bait. Quantitative studies and of transmission
      potentials were also performed. The following results were obtained: a) Absolute
      black flies densities (nulliparous and pariparous) and infected black flies (with
      L1 and L2 larvae): S. ochraceum, S. metallicum and S. callidum, in that order was
      the distribution of densities. Infected black flies were obtained in the 3
      species. However, in despite of an irregular distribution in all the year, it was
      possible to identify 2 peaks of maximum infection of S. ochraceum in March, 1979
      and March 1981. b) Monthly bite densities and infective bites.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1345119
TI  - [AIDS and HIV infection among homosexual and bisexual men in Belem, Para, Brazil,
      1988-1990].
AB  - During three years (1988-1990) blood samples from 307 people were taken to test
      antibodies for Human Immunodeficiency Virus type 1 (HIV-1) in homo and bisexual
      males living in Belem, being 149 (48.5%) of the former and 158 (51.5%) of the
      later. All patients requested examinations spontaneously to find out their
      status. The ages of tested people ranged from 16 to 64 years old. Serologic
      diagnosis was made using an enzyme immunoassay (Abbott, Sao Paulo-Brasil) for
      screening and an indirect immunofluorescence test (FIOCRUZ, Rio de Janeiro
      Brasil) for confirmation. If results were conflicting with these tests, western
      blot (Du Pont CO. Wilmington-USA) was performed to obtain a definitive result.
      Sixty-eight (22.1%) of all sera were positive. Although, the positivity in the
      homosexual group (26.2%) was more higher than in the bisexual group (18.3%). The
      positivity rate in both groups was directly proportional with the increase of
      age. Of course, people with less than 20 years old had only 3% of positivity,
      while between 20-29 had 18.1%, 30-39 had 34.5%, 40-49 had 40% and 50-59 had 50%.
      The projected curve of positivity, is progressive, that is to say, the risk of
      homo/bisexual males increases with age and is probably related to increased
      sexual activity. We conclude that more than one quarter of homosexual men are
      infected with HIV-1 in Belem.

PMID- 1345120
TI  - Chemically unrelated mycobacterial peptides as antigens and competitors in
      antigen recognition by human T cells.
AB  - Understanding resistance to mycobacterial infectious diseases requires
      identification of antigens and epitopes (antigenic determinants) that stimulate
      cell-mediated immune responses. In this study, a DR1-restricted T cell epitope
      (residues 1 through 20) of the 19-kD protein of M. tuberculosis was identified.
      Peripheral blood mononuclear cells from two HLA-DR1 patients with tuberculosis
      responded not only to the 19-kD immunoblot fraction of M. tuberculosis but also
      to the peptide 1-20. A M. tuberculosis-reactive T cell clone isolated from one of
      the patient (whose mononuclear cells showed a stronger proliferative response to
      the 19-kD protein) recognized the peptide 1-20, while failed to recognize a
      negative control peptide (residues 65 through 85 of the 65-kD mycobacterial
      protein: peptide 65-85) or a negative control antigen (candida). The antigen
      recognition to peptide 1-20 was shown to be DR1 restricted. This MHC restriction
      was confirmed using a DR1-restricted mycobacterial T cell epitope as competitor.
      These results demonstrated that this mycobacterial competitor significantly
      reduced the antigen recognition of peptide 1-20. The reduction observed was dose
      dependent.

PMID- 1345121
TI  - [Characterization fo mycelial mutants of Mucor rouxii].
AB  - The consequences of two different mutations induced with N-methyl-N
      nitrosoguanidine (Strain G1) and Trifluoperazine resistance (Strain G5) in Mucor
      rouxii, were studied. Mutants were stable and exhibited mycelial morphology in
      aerobiosis. Mutants cells exhibit phenotypic characteristics of slow-growing. The
      mutants G1 and G5 cultures showed 16.8% and 35.3% of reduction of the growth
      relative to parental strain. Morphologically mycelia of mutants cell were
      indistinguishable from wild-type cells, except from reduction in extension and
      branching of hyphal that has the mutant G5. Calcofluor and FITC-Concanavalin A
      were used to study the distribution of new cell-wall polymers i.e. Chitin,
      glucans. The two G1 and G5 strains showed a uniform distribution of fluorescence
      over the cell surface, indicating that active deposition of new-wall material has
      occurred. Cellular proteins of mutants and parental strains were labeled with 14C
      aminoacid mixture. The proteins pattern revealed that the majority of
      polypeptides synthesized by parental strain were also synthesized by mutants. It
      is evident the synthesis preferential of peptides with apparent M(r) > 92K, 60K,
      50K, 43K, 38K and 25K. These results indicated that the primary defect of the
      mutation was not on cellular differentiation. It discuss phenotypic and
      biochemistry characteristics from mutants.

PMID- 1345122
TI  - [In situ studies of myoinositol-1-P synthase in wild and inos- strains of
      Neurospora crassa].
AB  - The biosynthetic pathway for myo-inositol consist of two enzymatic steps: first,
      the cycloaldolization of glucose-6P to L-myo-inositol-IP followed by its
      hydrolysis to form free myo-inositol. The former reaction is catalyzed by myo
      inositol-IP synthase (MIPS) while, a phosphatase is responsible for the
      hydrolysis step. Depending on its degree of purification and storage age, MIPS
      activity us to be, from partial to fully, dependent on added NAD. Therefore, we
      decided to study the kinetic properties of the enzyme within the cell, specially
      its requirements for free NAD. To this purpose, a method was designed for the
      assay of MIPS-activity in situ, using toluene permeabilized mycelia. MIPS
      activity "in situ" was fully displayed in the absence of added NAD; on the
      contrary, the purified enzyme showed only 33% of that activity displayed when NAD
      was included in the assay. Thus, it seems that the native enzyme contains tightly
      bound NAD, instrumental for its activity, and that during purification or
      storage, the coenzyme is progressively lost, rendering the NAD-dependent enzyme,
      as was previously envisage. In addition, the in situ assay method for MIP
      Synthase was applied to several mutants of N. crassa having the inosphenotype.
      Our results showed that only in 3 of 14 cases analyzed the phenotype could be
      clearly associated to the lack of MIP-synthase activity. Indeed most of the
      mutants analyzed showed significant levels (from 5 to 21%) of MIP-synthase, when
      compared to the activity shown by the RL-21 WT strain. Finally, all the mutants
      and WT strains were zymographically analyzed for phosphatase activity and showed
      close to equal strong reaction levels.

PMID- 1345123
TI  - Destructive arthropathy of fingers in primary hypothyroidism without
      chondrocalcinosis. Report of 3 cases.
AB  - Three cases of undiagnosed primary hypothyroidism with high thyroid stimulating
      hormone values presented destructive arthropathy of the proximal interphalangeal
      joints. None had chondrocalcinosis, neuropathy, myopathy or sicca complex. Quick
      improvement followed hormonal therapy, which suggests that hormonal imbalance
      could be responsible for this particular rheumatic condition.

PMID- 1345124
TI  - Prevention of infective endocarditis associated with dental treatment and other
      medical interventions.

PMID- 1345125
TI  - Vibration white finger and Dupuytren's contracture: are they related?
AB  - Between 1988 and 1990, 500 claimants were assessed and considered to have
      vibration white finger (VWF). Of these, 137 were under 45 years of age and none
      had Dupuytren's contracture of the remaining 363, 311 were aged 50-85 years, and
      of these 62 (19.9 per cent) had Dupuytren's contracture. Statistically, this
      prevalence was significantly higher than that in a control group of 150 men of
      similar age distribution (10.7 per cent). As far as can be ascertained, this is
      the first study to indicate that there may be a causal relationship between VWF
      and Dupuytren's contracture, and the possible theoretical reasons for this are
      discussed. It is suggested that further studies are required to confirm or refute
      the findings.

PMID- 1345126
TI  - Surgical management of carcinoid heart disease.

PMID- 1345127
TI  - Reflections on home hemodialysis: the invisible modality.

PMID- 1345128
TI  - Hoarseness after tracheal intubation.

PMID- 1345129
TI  - Using videotape instruction and feedback to improve adolescents' mothering
      behaviors.
AB  - The effects of videotape instruction and feedback (videotherapy) on mothering
      behaviors were evaluated in this longitudinal study. In this study, 31
      adolescents and their healthy infants were randomly assigned to experimental and
      control groups. All subjects were videotaped during structured mother-infant
      teaching episodes in their homes at 1 and 2 months postpartum. Experimental group
      subjects reviewed the videotaped 1-month teaching episode and received feedback
      from a specially trained professional nurse who emphasized positive aspects of
      maternal behavior. Instruction was individualized according to the mother's
      needs. Results of a repeated measures MONOVA revealed significant differences in
      the pattern of change over time between subjects in the experimental and control
      groups on a measure of actual maternal behaviors. Adolescents receiving videotape
      instruction and feedback obtained significantly higher maternal behavior scores
      at 1 and 2 months postpartum.

PMID- 1345130
TI  - When the protest comes home: Ontario doctor latest victim of antiabortion
      picketing tactic.

PMID- 1345131
TI  - Asks for more information on self-mutilative behavior.

PMID- 1345132
TI  - Heparin therapy in Russell's viper bite victims with disseminated intravascular
      coagulation: a controlled trial.
AB  - A controlled clinical trial of low dose heparin was carried out in confirmed
      cases of Russell's viper bite. Twenty patients with systemic envenoming were
      included in the study. They were randomized to receive low dose heparin in an
      initial dose of 50 units/kg body weight intravenously immediately after antivenom
      followed by a continuous infusion of 10 unit 3 kg/hour in isotonic saline for 24
      hours, or antivenom alone. Response to treatment was assessed clinically as well
      as by serial measurements of coagulation factors and biochemical values. No
      significant difference was observed in the outcome among two groups, the recovery
      rate from the clotting defect being similar in both. The mean serum creatinine
      values of the two groups were also not statistically different. The results
      indicated that there is no beneficial effect of adding heparin to the standard
      treatment by antivenom.

PMID- 1345133
TI  - Naltrexone in the treatment of alcohol dependence.
AB  - Seventy male alcohol-dependent patients participated in a 12-week, double-blind,
      placebo-controlled trial of naltrexone hydrochloride (50 mg/d) as an adjunct to
      treatment following alcohol detoxification. Subjects taking naltrexone reported
      significantly less alcohol craving and days in which any alcohol was consumed.
      During the 12-week study, only 23% of the naltrexone-treated subjects met the
      criteria for a relapse, whereas 54.3% of the placebo-treated subjects relapsed.
      The primary effect of naltrexone was seen in patients who drank any alcohol while
      attending outpatient treatment. Nineteen (95%) of the 20 placebo-treated patients
      relapsed after they sampled alcohol, while only eight (50%) of 16 naltrexone
      treated patients exposed to alcohol met relapse criteria. Naltrexone was not
      associated with mood changes or other psychiatric symptoms. Significant side
      effects (nausea) occurred in two naltrexone-treated subjects, and one naltrexone
      treated subject complained of increased pain from arthritis. These results
      suggest that naltrexone may be a safe and effective adjunct to treatment in
      alcohol-dependent subjects, particularly in preventing alcohol relapse.

PMID- 1345134
TI  - Skin collagen changes related to age and hormone replacement therapy.
AB  - A total of 76 nulliparous women who had been hospitalized for minor operations,
      classified according to age group (by decade from 20s to 60s) and 118
      postmenopausal women randomly allocated to one of four groups were studied. In
      all, 312 skin biopsies were taken from the lower abdomen at 0 and 12 months and
      the skin collagen changes noted. Collagen content decreased significantly with
      age beyond the 40s (P < 0.001) and after the menopause (P < 0.01). The decrease
      was preventable by the use of hormone replacement therapy. All the therapeutic
      regimens induced increases in skin collagen content, whereas in the control group
      a significant decrease was observed (P < 0.05).

PMID- 1345135
TI  - Guttate parapsoriasis/digitate dermatosis (small plaque parapsoriasis) is mycosis
      fungoides.
AB  - Authors of most textbooks of dermatology and dermatopathology consider guttate
      parapsoriasis and digitate dermatosis to be variants of small plaque
      parapsoriasis which, they aver, is not related to mycosis fungoides. On the basis
      of a study of clinical and histopathologic findings in guttate parapsoriasis and
      digitate dermatosis, we conclude that those conditions actually represent two of
      the many clinical faces of mycosis fungoides.

PMID- 1345136
TI  - Overdose with sustained-release lithium preparations.
AB  - Two cases of overdose with sustained-release lithium preparations are presented.
      Initial serum lithium levels were in the therapeutic or subtherapeutic range.
      Subsequent levels were in the toxic range. These cases illustrate the potential
      danger of delayed toxicity with ingestion of these agents.

PMID- 1345137
TI  - Preventive care of elderly people.

PMID- 1345138
TI  - Radiographic evidence of disease progression in methotrexate treated and
      nonmethotrexate disease modifying antirheumatic drug treated rheumatoid arthritis
      patients: a meta-analysis.
AB  - Methotrexate (MTX) has proven to be efficacious in the treatment of rheumatoid
      (RA), but it remains to be proven whether it can slow disease progression, as
      determined radiographically, in comparison with other disease modifying
      antirheumatic drugs (DMARD). We performed a meta-analysis of the available data
      to answer this question. A literature search, including abstracts, was conducted
      and inclusion criteria developed (description of patients, accountability of
      patients, inclusion of a control group of patients, specified radiographic
      endpoint, and appropriate reading of the radiographs). Publications were scored
      on a scale of 0 to 5 with a score > or = 3 required for inclusion in the study.
      For abstracts selected, additional data were obtained directly from the
      investigators. Data for 353 MTX treated and 205 non-MTX-DMARD treated patients
      with RA were gathered. Not all publications used the same scoring system, so some
      assumptions were required to analyze the combined data. Only the erosion score
      was included since not all publications included a reading of the joint space.
      All scores were transformed into Sharp scores (Arthritis Rheum 1985;28:1449),
      including the important contributions of 3 Larsen scored publications. Finally a
      monthly rate of disease progression was computed. Several comparisons were made.
      Overall, the rates of disease progression were similar for MTX and non-MTX-DMARD
      treated patients with RA. The non-MTX-DMARD treated patients with RA were
      separated into a group treated with gold salts (oral or parenteral) and a group
      treated with azathioprine with each group compared to the MTX treated patients.
      MTX had slower rates of disease progression than azathioprine, (rates 0.004 vs
      0.012) but not slower rates than gold salts (0.008 vs 0.008). Despite its
      efficacy, the possible role of MTX in slowing disease progression more than other
      DMARD, as determined radiographically, appears to be evident only when compared
      to azathioprine.

PMID- 1345139
TI  - Prophylaxis of infective endocarditis.

PMID- 1345140
TI  - Correlates of the estimated arterial compliance in the population of Tecumseh,
      Michigan.
AB  - An estimate of arterial compliance--the stroke volume/pulse pressure ratio
      (SV/PP)--was studied in 801 participants in the Tecumseh Blood Pressure Study, a
      population-based ongoing cardiovascular, epidemiological investigation. The
      subjects were normal young adults (mean age 30 +/- 5.6 years) and 373 were
      females. Cardiac anatomy and function were studied by echo-Doppler methods, blood
      pressure being measured at the same time by the indirect method. The distribution
      of the SV/PP ratio was skewed toward higher values in larger subjects. After
      statistical adjustments for body surface area, this estimate of arterial
      compliance was found to be higher in females (2.00 +/- 0.62) than in males (1.90
      +/- 0.58) (p < 0.05). When subjects were divided into tertiles, the group with
      the lowest estimated arterial compliance was normotensive but had higher systolic
      pressure, lower diastolic pressure, a similar mean arterial pressure, higher
      heart rate and higher left ventricular wall thickness ratio compared to subjects
      with higher arterial compliance. Indices of systolic ejection decreased and
      diastolic function was altered in the low compliance subjects. In addition, low
      compliance subjects also had higher fasting insulin levels. These findings
      suggest that the low arterial compliance in an otherwise normal population has
      negative cardiovascular correlates. The early association of decreased arterial
      compliance with anatomic, functional and biochemical aberrations suggests that
      estimates of arterial compliance might prove useful for prediction of
      cardiovascular complications.

PMID- 1345141
TI  - Hypertensive retinal vascular changes: relationship to left ventricular
      hypertrophy and arteriolar changes before and after treatment.
AB  - Eye-ground-photos were taken in twenty-eight previously untreated men with mild
      to moderate essential hypertension. The same eye was evaluated before and after
      26 weeks of double-blind treatment with Enalapril or Hydrochlorothiazide. The
      vascular changes were assessed by using a more elaborate and refined grading than
      the Keith-Wagener-Barker scale. All photos were examined by the same observer
      without knowledge of blood pressure, type of treatment or the order in which the
      photos had been taken. There were significant positive correlations between the
      vascular alterations in the retina in the untreated state and left ventricular
      wall thickness (echocardiography), minimal vascular resistance in the calf
      (plethysmography) and blood pressure respectively. Treatment with Enalapril
      decreased the reflection of the retinal arterial wall significantly and reduced
      the narrowing of arteries and arterio-venous crossing phenomena non
      significantly. Hydrochlorothiazide did not affect any of the retinal vascular
      changes. It can be concluded that this relatively simple technique of evaluating
      eye-ground-photos with a new grading scale, when used in non-malignant
      hypertension, gives a useful assessment of the degree of hypertensive target
      organ damage in the retina as well as in other important target organs, i.e. the
      heart and vascular beds. In addition, Enalapril positively affects hypertensive
      retinopathy in contrast to Hydrochlorothiazide, reflecting what happens to
      structural cardiovascular changes in the rest of the body.

PMID- 1345143
TI  - Some reflections on today's hypertension research.

PMID- 1345142
TI  - Contractions to endothelin in normotensive and spontaneously hypertensive rats:
      role of endothelium and prostaglandins.
AB  - Contractions to endothelin-1 in aortas of the spontaneously hypertensive rats
      (SHR) were compared with those of normotensive controls (WKY); rings with and
      without endothelium were studied in organ chambers. Contractions to endothelin
      were smaller in aortas of SHR compared to WKY, whether the endothelium was
      present or not. The presence of a functional endothelium reduced contractions to
      the peptide in both strains. Endothelium-dependent relaxations to acetylcholine
      and endothelium-independent relaxations to nitric oxide were observed in rings
      from both strains during contraction with endothelin. Indomethacin reduced the
      contractions to endothelin in the aorta from SHR with endothelium, but not in
      those without endothelium; it did not significantly affect endothelin-induced
      contractions in rings of WKY with or without endothelium. These experiments
      demonstrate that contractions of the vascular smooth muscle to endothelin are
      reduced in the aorta of the SHR. The basal and stimulated release of endothelium
      derived relaxing factor inhibits contractions to endothelin in the aorta from
      both strains. The inhibitor of cyclooxygenase indomethacin does not prevent the
      response of the vascular smooth muscle to endothelin; however, endothelin may
      stimulate the release of an indomethacin-sensitive endothelium-derived
      contracting factor in the SHR aorta.

PMID- 1345144
TI  - Raised plasma concentrations of endothelin-1 and -3 in marmosets with acute
      aortic stenosis: no relation to the renin-angiotensin system.
AB  - Plasma levels of endothelin (ET), plasma renin activity (PRA) and angiotensin II
      (Ang II) were measured in anaesthetized marmosets exposed to acute aortic
      stenosis proximal to the renal arteries. In vehicle experiments, ET rose from 5
      +/- 2 to 38 +/- 4 pg ml-1, PRA from 5 +/- 2 to 99 +/- 21 ng ml-1 h-1 and Ang II
      from 21 +/- 4 to 213 +/- 76 pg ml-1. Administration of renin inhibitor and
      angiotensin converting enzyme inhibitor reduced PRA and Ang II to control levels,
      while the plasma levels of ET increased further (51 +/- 10 and 71 +/- 16 pg ml-1,
      respectively). During aortic stenosis the two isoforms ET-1 and ET-3 appeared in
      the circulation, while in conscious control animals only ET-1 was found. It is
      concluded that the increased plasma levels of ET in our primate model could not
      be ascribed to the increased circulating levels of PRA and Ang II.

PMID- 1345146
TI  - [Index 1885-1991].

PMID- 1345145
TI  - The interconnection between sympathetics, microcirculation, and insulin
      resistance in hypertension.
AB  - The pathophysiology of the frequent association of insulin resistance and
      hypertension has not been elucidated. The skeletal muscle is the major site of
      insulin resistance; when stimulated with insulin, the hypertensive skeletal
      muscles extract less glucose than the normotensive. We postulate that
      hypertension-related changes in the skeletal muscle microcirculation contribute
      to the impaired glucose uptake in hypertension. Vascular rarefaction in
      hypertension impairs the delivery of insulin and glucose to muscle cells. Insulin
      resistance has been described both in human and experimental hypertension and
      both conditions are associated with vascular rarefaction. Functional studies
      (response to whole body or forearm exercise) and anatomic investigations
      (conjunctival photography, mesenteric and muscle biopsies) show vascular
      rarefaction in human hypertension. In addition, patients with hypertension are
      known to have a larger proportion of insulin resistant, poorly vascularized fast
      twitch muscle fibers. A few interventions can increase or decrease insulin
      resistance and these effects can be explained on hemodynamic grounds. Beta
      adrenergic blocking agents aggravate insulin resistance, and their main
      hemodynamic effect is a decrease of cardiac output. Converting enzyme inhibitors,
      alpha adrenergic blocking agents and possibly calcium antagonists decrease the
      insulin resistance, and their major hemodynamic effect is vasodilation. Physical
      training decreases insulin resistance; a higher capillary density in skeletal
      muscles is the hallmark of physical training. A hypothesis ought to rest on
      sufficient supporting data and its validity ought to lend itself to experimental
      verification. We believe our hypothesis meets both criteria. After outlining the
      supporting evidence we propose a number of tests to prove or disprove the
      hypothesis. In addition to the testable hypothesis we also speculate on the
      possible cause of the frequent association between hypertension and insulin
      resistance. We propose that both insulin resistance and blood pressure elevation
      represent a facet of the "defense reaction" which might have offered an early
      survival advantage and may, over evolutionary times, have fostered natural
      selection of subjects with both conditions.

PMID- 1345147
TI  - Clinical guidelines. Report of a local initiative. Introduction.

PMID- 1345148
TI  - Asthma.
AB  - 1. Asthma is defined as variable wheezy breathlessness. Cough rather than
      wheezing may be a presenting symptom, especially in children. Many asthmatics
      have predominantly nocturnal symptoms. 2. A severe attack is suggested by any of
      the following factors: a respiratory rate of > 25 breaths/minute, a tachycardia
      of > 110 beats/minute, a reduction by more than 40% in the normal peak expiratory
      flow rate (PEFR) or less than 200 l/min if usual PEFR not known), an inspiratory
      fall in arterial blood pressure of 10 mmHg. 3. The initial treatment of an acute
      attack includes nebulized beta 2 agonist bronchodilators. A pressurized aerosol
      given by a Volumatic or Nebuhaler device may also be effective. A short course of
      steroids should be initiated promptly starting with 30-60 mg of oral prednisolone
      as a single dose. Intravenous aminophylline should not be given to patients
      taking oral theophylline or aminophylline. 4. Signs of an imminent threat to life
      include: a silent chest on auscultation, cyanosis, bradycardia, exhaustion,
      confusion, or unconsciousness. 5. Indications for urgent referral to hospital
      include a PEFR < 40% of normal (or less than 200 l/minute for adults) 15-30
      minutes after nebulized salbutamol, any life-threatening features and if any
      other features of a severe attack persist after initial treatment. The threshold
      for admission will also be affected by the social circumstances. 6. The first
      line treatment of chronic asthma is inhaled beta 2 agonists. Correct inhaler
      techniques should be reinforced on several occasions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1345149
TI  - Chronic obstructive airways disease.
AB  - 1. Chronic obstructive airways disease is a term which should be reserved for
      those who have objective evidence of airways obstruction and who do not improve
      significantly with bronchodilators or steroids. All patients should have a trial
      of aggressive treatment with these drugs in case they have chronic asthma. 2. All
      patients should be urged strongly to give up smoking. 3. There is no scientific
      evidence that slow release aminophylline or theophylline are of benefit in these
      patients, and they may be hazardous in those with coronary artery disease. 4.
      Acute infective exacerbations may be due to haemophilus influenzae or
      pneumococcus; patients with fever should be given co-trimoxazole, ampicillin, co
      amoxiclav or erythromycin (co-trimoxazole should generally be avoided in the
      elderly). 5. Domiciliary oxygen therapy, given for at least 12 and preferably 16
      hours a day, will prolong survival in patients with Type II respiratory failure
      ('blue bloaters'). It may help symptoms in Type I respiratory failure ('pink
      puffers'). It should only be prescribed after blood gas measurements and the
      patient must therefore be referred.

PMID- 1345150
TI  - Chronic heart failure.
AB  - 1. The common symptoms and signs of chronic heart failure are dyspnoea, ankle
      swelling, raised jugular venous pressure and basal crepitations. Other conditions
      may be confused with chronic heart failure, including dependent oedema or oedema
      due to renal or hepatic disease. Shortness of breath may be due to respiratory
      disease or severe anaemia. Heart failure secondary to lung disease (cor
      pulmonale) should be distinguished from congestive cardiac failure. Heart failure
      may also present with less common symptoms including: cough, anorexia and weight
      loss, hepatic capsule pain and confusion. 2. Once heart failure is recognized, an
      attempt should be made to determine the underlying cause which may include
      valvular abnormalities, altered cardiac rhythm, specific heart muscle disease,
      coronary artery disease and hypertension. 3. Investigations initiated by the
      general practitioner include ECG, chest x-ray, full blood count (FBC), mean
      corpuscular volume (MCV), gamma transferase (GTT), creatinine and electrolytes,
      thyroxine. 4. If no underlying cause is found then referral should be considered
      in those under 75 and those aged 75 and over who fail to respond to treatment. 5.
      It is important to encourage patients to stop smoking, reduce weight and, where
      appropriate, alcohol consumption. Added salt should be avoided. 6. Digoxin should
      be prescribed to control the ventricular rate in those with atrial fibrillation.
      Renal function and potassium should be checked beforehand and the dose of digoxin
      adjusted to take into account any renal impairment. 7. Bendrofluazide is
      recommended in doses of not more than 10 mg (5 mg in the elderly). Potassium
      supplements may be required for those at high risk from hypokalaemia, including
      patients taking digoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345151
TI  - Hypertension.
AB  - 1. Accurate measurement of blood pressure using a regularly serviced
      sphygmomanometer is essential. 2. Severe hypertension requires early treatment.
      Uncomplicated mild to moderate hypertension requires repeated blood pressure
      measurements up to three or four months before the diagnosis is confirmed. 3.
      Personal and family histories, relevant examination and investigations precede
      treatment. 4. Initial management should aim at reducing weight, improving diet
      and exercise, and stopping cigarette and excess alcohol consumption. 5. Patients
      with other risk factors require drug treatment at an earlier stage and at lower
      blood pressure levels. Essential hypertension is associated with an increased
      prevalence of risk factors which may need attention. 6. Treatment of asymptomatic
      hypertension should be considered in patients up to the age of 80. 7. First-line
      treatment: thiazide diuretics and beta blockers, used in the lowest effective
      doses, are of proven value and acceptability. The former are by far the cheapest
      antihypertensive drugs. 8. Second-line treatment: if thiazides and beta blockers
      are contra-indicated or ineffective, ACE inhibitors, calcium antagonists and
      alpha blockers should be used. With drugs of these classes the absence of adverse
      cardiovascular metabolic effects is a theoretical advantage but of uncertain
      magnitude. 9. Follow-up of patients with borderline levels of raised blood
      pressure as well as for those on treatment is essential.

PMID- 1345152
TI  - Irritable bowel syndrome.
AB  - 1. Irritable bowel syndrome is a functional disorder of the lower intestinal
      tract affecting approximately 10% of the population and causing a wide range of
      symptoms. 2. Most cases of irritable bowel syndrome can be diagnosed in general
      practice on the basis of the presenting history and clinical examination but some
      patients may need to be referred to a gastro-enterologist for further assessment
      including sigmoidoscopy and barium enema. 3. The clinical picture may include
      symptoms of abdominal pain and/or distension and altered bowel habit. Nausea,
      dyspepsia, gynaecological or bladder symptoms are also common. About a third of
      patients may give a family history of recurrent abdominal pain. 4. Clinical signs
      include general anxiety, scars on the abdomen (from previous laparotomies for
      severe abdominal pain), a palpable and tender left colon or generalized abdominal
      tenderness, and loud borborygmi. 5. Absolute indications for a specialist
      assessment are: weight loss rectal bleeding onset of symptoms after the age of 40
      a mass. Even in the absence of any of these findings referral is frequently
      necessary to allay patient anxiety and reinforce the diagnosis. 6. Blood tests
      are usually non-contributory. Stool specimens should be sent if diarrhoea is a
      feature. 7. A full explanation emphasizing the benign and often recurrent nature
      of the condition should be given to help patients understand the nature of their
      symptoms. Only after review of lifestyle and advice about diet have been provided
      should drug therapy be tried.

PMID- 1345153
TI  - Back pain.
AB  - 1. Back pain is very common and can be the result of a wide range of different
      conditions. A detailed history of the complaint often points towards the cause.
      Positional backache suggests a mechanical cause, unremitting pain may indicate
      malignancy or infection especially if accompanied by night sweats, whereas
      morning stiffness is more often the result of inflammation. 2. Examine the
      patient lying and standing as outlined. A general examination should also be
      performed if there is a history of weight loss, night sweats, or if the patient
      looks ill. 3. The vast majority of cases of backache are mechanical in origin.
      Plain x-rays are not normally contributory and should be avoided unless there are
      factors in the history and examination suggestive of infection or malignancy. 4.
      Patients with backache and sphincter disturbance and/or perineal anaesthesia
      require immediate hospital admission. 5. Analgesia and bed rest are the mainstays
      of treatment for acute backache of mechanical origin. Once there has been some
      improvement, physiotherapy can be beneficial. 6. Chronic back pain is present if
      the complaint lasts for more than 8 weeks. Investigations should include full
      blood count, ESR, calcium and alkaline phosphatase. The patient needs to be
      referred to a rheumatologist or orthopaedic surgeon for further assessment and
      possible imaging studies. If no cause other than mechanical dysfunction is found
      the patient should be assessed by a physiotherapist and taught back care.

PMID- 1345154
TI  - Management of heavy drinkers.
AB  - 1. The amount of alcohol consumed per capita in the UK has approximately doubled
      since 1950. 2. One unit of alcohol is equivalent to around 8 g of pure alcohol
      (half a pint of beer, a single bar measure of spirits or glass of wine). 3.
      Consumption of above 21 units a week for men and 14 units a week for women
      carries an increasing risk of alcohol-related damage. Pregnant women are usually
      advised to abstain. 4. Newly registered patients should be asked if they have
      consumed any alcohol in the last three months and if so how much they consume in
      an average week using a quantity frequency scale. 5. In those in whom there is
      concern about their drinking a systematic 7-day history gives the best estimate
      of consumption. 6. Heavy drinking should also be considered in a wide range of
      clinical circumstances, including hypertension, injuries and accidents, marital
      disharmony and child abuse, dyspepsia, hepatic damage, memory impairment and
      dementia. Sudden withdrawal may cause fits which may lead to a mistaken diagnosis
      of epilepsy. 7. Laboratory tests pick up only 30-50% of heavy drinkers but may be
      useful in monitoring progress and in motivating patients to cut down. 8. It is
      important to decide whether a patient is dependent on alcohol as dependent
      drinkers are unlikely to be able to keep their consumption at modest levels. The
      possibility of psychological and social problems due to alcohol should also be
      considered. The use of drugs should be explored in dependent drinkers.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1345155
TI  - Drug misuse.
AB  - 1. Assessment by history and examination should include: a history of all drugs
      taken during each day for the previous 7 days (including alcohol), length of drug
      use and route (including the sharing of needles or syringes), the possibility of
      pregnancy if female, previous psychiatric history and treatment of drug misuse,
      social factors (including employment, family, friends, involvement in
      prostitution, legal problems), medical problems, including evidence of hepatitis,
      injection abscesses and other infections, suicide attempts, and weight loss. 2.
      Notification to the Chief Medical Officer of the Drug Branch of the Home Office
      is a legal obligation. 3. Investigations include: liver function tests (LFTs),
      hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb),
      hepatitis C antibody, full blood count (FBC), and urine for drug screening.
      Consider HIV testing if at risk but it is usually better arranged at a later
      stage. 4. Prescribing may be considered for a variety of drugs but objectives
      will differ according to drug type and individual. 5. In the case of opioid
      users, prescribing may be useful to stabilize their lives and to promote
      attendance for professional help. It may reduce high risk behaviour for
      contracting and spreading HIV. 6. If medication is given to opioid users,
      methadone mixture 1 mg/ml given once a day is the prescription of choice.
      Dispensing should be on a daily basis and the blue prescription form FP10 (MDA)
      allows the chemist to dispense daily for up to 14 days. A maximum ceiling of 100
      mg methadone/day should not be exceeded. The initial dose will depend on the
      amount of opioid consumed in the previous week.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345156
TI  - Common skin conditions.
AB  - Four common conditions: acne, psoriasis, eczema and urticaria are considered.
      Guidance is given on appropriate topical and systematic treatment for the
      different types and degrees of these conditions, with notes on management in
      general and criteria for referral to hospital outpatient departments. Where there
      are different types of the condition, with varying aetiology, for example in
      urticaria and eczema, management of the common types is outlined.

PMID- 1345157
TI  - Red or uncomfortable eye.
AB  - 1. A red, uncomfortable eye may be accompanied by other symptoms such as blurred,
      decreased, or double vision, haloes, photophobia, pain or discharge. 2. A careful
      history and brief systematic examination will sort out most problems. 3. Examine
      eyelids, the conjunctivae and corneas. Checking visual acuity is often important.
      4. The most common underlying causes can usually be managed within general
      practice, though a few patients will require urgent eye assessment, or routine
      referral to ophthalmic outpatients. 5. The following are typical eye problems
      which require urgent referral: History of pain as opposed to discomfort, Trauma
      including foreign bodies, chemicals and suspected penetrating injury, Unexplained
      drop in visual acuity of two lines or more in a painful eye. Specific conditions:
      preseptal cellulitis, herpes simplex ulcer, scleritis, orbital cellulitis, herpes
      zoster, bacterial corneal ulcer, dacryocystitis. 6. The following are typical
      problems which may require routine referral: Persistence of the problem not
      relieved by simple measures, Recurrent disorders of uncertain diagnosis, Eyelid
      swelling such as chalazion, cysts, basal cell carcinoma, Gradual loss of vision,
      for example cataract, macular degeneration.

PMID- 1345158
TI  - Dementia in old age.
AB  - 1. About 10% of patients aged 75 and over are demented to an appreciable degree;
      the proportion may exceed 20% in those over 85. 2. Potentially reversible causes
      include pernicious anaemia, hypothyroidism, frontal meningioma, and normal
      pressure hydrocephalus. In many cases, however, treatment has little effect on
      cognitive function. 3. Around 50% are due to Alzheimer's disease, 20% to multi
      infarct dementia, and a further 15-20% have both conditions. 4. Recognition is
      facilitated by using a standard test of cognitive function (the Abbreviated
      Mental Test Score or the Mini Mental State Examination). 5. Dementia must be
      distinguished from delirium and depression. 6. Investigations by the general
      practitioner include full blood count and TSH. Urine should be tested,
      particularly if there is incontinence. Physical examination should exclude
      intercurrent disease and check for neurological deficits. 7. Sudden onset of
      confusion without obviously remediable cause and the need for respite care are
      indications for referral. Patients may also be referred for initial assessment.
      8. An individually tailored care package should be designed for each patient. It
      should be clear who is taking responsibility for follow-up and monitoring. 9.
      Carers should be supported, encouraged to ventilate their feelings, put in
      contact with appropriate voluntary groups, advised on appropriate allowances, and
      offered respite care when needed.

PMID- 1345159
TI  - Prevention of cardiovascular disease.
AB  - 1. Major risk factors for coronary heart disease (CHD) are smoking, blood
      pressure and blood cholesterol and they interact in a multiplicative fashion.
      Family history of premature coronary heart disease and lack of exercise also
      contribute. Obesity increases risk probably mainly by its effect on blood
      cholesterol and blood pressure. Heavy alcohol consumption is a risk factor for
      stroke. 2. Prevention may be opportunistic or in specially organized clinics, the
      latter being less likely to result in the attendance of high risk individuals. 3.
      Worthwhile reductions in cigarette smoking can be achieved by brief advice and
      follow-up. Literature on smoking and other aspects of prevention is available
      from the district health education department. 4. Risk scores can be used to
      calculate the risk of coronary heart disease. They can help to indicate the
      advisability of measurement of blood cholesterol and to focus limited resources
      on those at highest risk by helping to define a 'special care group'. 5.
      Indications for measuring blood cholesterol are: a family history of premature
      coronary heart disease or hyperlipidaemia, personal history of coronary heart
      disease, clinical evidence of raised lipids (xanthelasma, corneal arcus under 50,
      xanthomas at any age), a high risk of coronary heart disease according to a risk
      score. Many would also include those under treatment for hypertension and
      diabetes. 6. Dietary advice can moderately reduce blood cholesterol. The
      proportion of calories from fat should be reduced from the current average of
      around 40% to a maximum of 33%. Dietary advice should be tailored to the
      patient's current diet. An increase in vegetables and fruit can be generally
      advocated. 7. Regular exercise has a worthwhile role to play in prevention. Rapid
      walking, jogging and swimming may all be suitable, as may be heavy gardening and
      housework. 8. A small proportion of patients may require lipid-lowering drugs.
      These include resins (cholestyramine and colestipol), fibrates (eg bezafibrate
      and gemfibrozil) and more recently HMG CoA inhibitors (eg simvastatin). The HMG
      CoA inhibitors produce large falls in cholesterol and may become first line drugs
      in future. Because of the current controversy about the effect of lipid-lowering
      drugs on total mortality, many believe that they should be reserved for those at
      the highest risk, for example patients with familial hypercholesterolaemia or
      with pre-existing coronary heart disease and a high plasma cholesterol (> 7.8
      mmol/L). 9. The special care group defined by the practice should be offered
      regular follow-up.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1345160
TI  - Diabetes mellitus.
AB  - 1. Diabetes mellitus is diagnosed by finding a random plasma glucose > 11 mmol/L,
      or a fasting plasma glucose > 8 mmol/L. The prevalence in the general population
      is between 1-2% rising to approximately 4-9% in the age group 65+ (Williams,
      1985; Croxson et al., 1991). It is more prevalent in people from the Indian
      subcontinent and in Afro-Caribbeans. 2. Approximately 75% of patients can be
      treated without recourse to insulin. The development of non-fasting ketonuria
      and/or significant weight loss suggests the onset of insulin dependence. These
      patients should be referred for specialist advice rapidly. 3. Chronic,
      uncontrolled hyperglycaemia greatly increases the risk of developing diabetic
      eye, nerve and kidney complications. 4. Treatment and follow-up aim: to abolish
      symptoms, to prevent and/or treat diabetic complications, to promote self-care
      and self-monitoring by patients, to avoid iatrogenic problems from overtreatment,
      to promote optimum nutrition for these patients. 5. Advice and assessment from
      the following specialists need to be built into the treatment plan: dietitian,
      competent fundoscopist (eg optometrist, general practitioner, hospital specialist
      depending upon local circumstances), chiropodist, diabetes education nurse and
      diabetes nurse specialist. 6. All patients need appropriate education about: the
      nature of diabetes mellitus, the importance of good control and the early
      detection of complications, a healthy lifestyle, the consequences of diabetes for
      driving and insurance. 7. All patients with diabetes should be reviewed
      clinically at least once a year. Diet, understanding of diabetes, self
      monitoring, metabolic control and complications should be assessed. More frequent
      clinical review is required in poorly controlled patients, or those with
      significant complications, or intercurrent illness.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1345161
TI  - Cervical cytology.
AB  - 1. Unless there are special clinical indications, regular cervical screening
      should begin at about the age of 20 and finish at 65. 2. Women aged 40 and over
      who have never had a smear should be actively encouraged to have a smear as soon
      as is practicable. 3. An Aylesbury spatula can be used, but the use of a
      cytobrush cuts down the proportion of smears reported as 'no endocervical cells
      seen'. 4. Most family health services authorities (FHSA) provide 3- or 5-yearly
      recall of women with normal smears and many practices have their own recall
      systems. District health authorities provide cytology and colposcopy services.
      The major part of the screening programme is undertaken in general practice. 5.
      The cervical screening policy of one district health authority is outlined. This
      is based upon the Intercollegiate Report issued by the Royal College of
      Obstetricians and Gynaecologists. 6. Different possible smear results are
      described together with appropriate patient management. Because these
      recommendations are likely to change in the light of new studies, general
      practitioners must be alert to the management advice offered by the cytology
      laboratory on abnormal smears. 7. For some women, FHSA recall may be more
      frequent than 3-yearly if instructed by the general practitioner. 8. Follow-up of
      abnormal smear results is the responsibility of the doctor who takes the smear.

PMID- 1345162
TI  - Shake that 'body map'.

PMID- 1345163
TI  - Extending the capabilities of interphase chromatin mapping.

PMID- 1345164
TI  - Large scale cDNA sequencing for analysis of quantitative and qualitative aspects
      of gene expression.
AB  - Large scale sequencing of cDNAs provides a complementary approach to structural
      analysis of the human genome by generating expressed sequence tags (ESTs). We
      have initiated the large-scale sequencing of a 3'-directed cDNA library from the
      human liver cell line HepG2, that is a non-biased representation of the mRNA
      population. 982 random cDNA clones were sequenced yielding more than 270
      kilobases. A significant portion of the identified genes encoded secretable
      proteins and components for protein-synthesis. The abundance of cDNA species
      varied from 2.2% to less than 0.004%. Fifty two percent of the mRNA were abundant
      species consisting of 173 genes and the rest were non-abundant, consisting of
      about 6,600 genes.

PMID- 1345165
TI  - Single pass sequencing and physical and genetic mapping of human brain cDNAs.
AB  - We have performed single pass sequencing of 1,024 human brain cDNAs, over 900 of
      which seem to represent new human genes. Library prescreening with total brain
      cDNA significantly reduced repeated sequencing of highly represented cDNAs. A
      subset of sequenced cDNAs were physically mapped to their chromosomal locations
      using gene-specific STS primers derived from 3' untranslated regions. We have
      also determined that human brain cDNAs represent a rich source of gene-associated
      polymorphic markers. Microsatellite-containing cDNAs can be physically mapped and
      converted to highly informative genetic markers, thus facilitating integration of
      the human physical, expression and genetic maps.

PMID- 1345166
TI  - Human genes containing polymorphic trinucleotide repeats.
AB  - Expansions of trinucleotide repeats within gene transcripts are responsible for
      fragile X syndrome, myotonic dystrophy and spinal and bulbar muscular atrophy. To
      identify other human genes with similar features as candidates for triplet repeat
      expansion mutations, we screened human cDNA libraries with repeat probes and
      searched databases for transcribed genes with repeats. From both strategies, 40
      genes were identified and 14 characterized. Five were found to contain repeats
      which are highly polymorphic including the N-cadherin, BCR, glutathione-S
      transferase and Na+/K+ ATPase (beta-subunit) genes. These data demonstrate the
      occurrence of other human loci which may undergo this novel mechanism of
      mutagenesis giving rise to genetic disease.

PMID- 1345167
TI  - X inactivation in mammalian testis is correlated with inactive X-specific
      transcription.
AB  - X chromosome inactivation occurs twice during the mammalian life cycle. In
      females one of the two X chromosomes of somatic nuclei is inactive, while in
      males the solitary X chromosome is inactivated during germ cell development.
      Despite the different properties of the inactivated chromosomes of females and
      males, the molecular initiation of inactivation may be the same. X inactive
      specific transcripts, XIST, are produced from somatic inactivated X chromosomes.
      We demonstrate here the existence of XIST transcripts in testes of man and mouse.
      Inactivation of X chromosomes in males, as in females, may thus be mediated
      through XIST. Conceivably, the silencing of X-linked genes is the price paid for
      the evolution of successful mechanisms of chromosomal sex determination.

PMID- 1345168
TI  - Expression of the X-inactivation-associated gene XIST during spermatogenesis.
AB  - Mammalian X-chromosome inactivation is thought to be controlled by the X
      inactivation centre (XIC, X-controlling element -Xce-in mice). A human gene, XIST
      and its mouse counterpart, Xist, which map to the XIC/Xce, are expressed
      exclusively from inactive X chromosomes, suggesting their involvement in the
      process of X-inactivation. We now report the presence of Xist/XIST transcripts in
      newborn and adult mouse testes, and in human testicular tissue with normal
      spermatogenesis, but not in the testes of patients who lack germ cells. Our
      results indicate that while the X chromosome in males is active in somatic cells,
      it undergoes inactivation during spermatogenesis.

PMID- 1345169
TI  - Expression of Xist in mouse germ cells correlates with X-chromosome inactivation.
AB  - Mammals compensate for different doses of X-chromosome-linked genes in male (XY)
      and female (XX) somatic cells by terminally inactivating all but one X chromosome
      in each cell. A transiently inactive X chromosome is also found in germ cells,
      specifically in premeiotic oogenic cells and in meiotic and postmeiotic
      spermatogenic cells. Here we show that the Xist gene, which is a expressed
      predominantly from the inactive X-chromosome in female somatic cells, is also
      expressed in germ cells of both sexes, but only at those stages when an inactive
      X chromosome is present. This suggests support for the putative role of Xist as a
      regulator of X-chromosome inactivation and suggest a common mechanism for the
      initiation and/or maintenance of X-chromosome inactivation in all cell types.

PMID- 1345171
TI  - Insulin gene region-encoded susceptibility to type 1 diabetes is not restricted
      to HLA-DR4-positive individuals.
AB  - Type 1 or insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease of
      the insulin-producing pancreatic beta-cells which is determined by both genetic
      and environmental factors. The major histocompatibility complex and the insulin
      gene region (INS) on human chromosomes 6p and 11p, respectively, contain
      susceptibility genes. Using a mostly French data set, evidence for linkage of INS
      to IDDM was recently obtained but only in male meioses (suggesting involvement of
      maternal imprinting) and only in HLA-DR4-positive diabetics. In contrast, we find
      evidence for linkage in both male and female meioses and that the effect of the
      susceptibility gene(s) in the INS region is not dependent on the presence of HLA
      DR4.

PMID- 1345170
TI  - Linkage disequilibrium mapping in isolated founder populations: diastrophic
      dysplasia in Finland.
AB  - Linkage disequilibrium mapping in isolated populations provides a powerful tool
      for fine structure localization of disease genes. Here, Luria and Delbruck's
      classical methods for analysing bacterial cultures are adapted to the study of
      human isolated founder populations in order to estimate (i) the recombination
      fraction between a disease locus and a marker; (ii) the expected degree of
      allelic homogeneity in a population; and (iii) the mutation rate of marker loci.
      Using these methods, we report striking linkage disequilibrium for diastrophic
      dysplasia (DTD) in Finland indicating that the DTD gene should lie within 0.06
      centimorgans (or about 60 kilobases) of the CSF1R gene. Predictions about allelic
      homogeneity in Finland and mutation rates in simple sequence repeats are
      confirmed by independent observations.

PMID- 1345172
TI  - Delineation of a 50 kilobase DNA segment containing the recombination site in a
      sporadic case of Huntington's disease.
AB  - No detectable rearrangements involving chromosome 4p16.3 have been observed in
      patients with Huntington's disease (HD). New mutations for HD could involve
      structural alterations which might aid the localization of the defective gene. We
      have reinvestigated a well documented sporadic case of HD. DNA haplotyping with
      markers between D4S10 and the telomeric locus D4S141 reveals a recombination
      event in one chromosome of the sporadic HD patient. The site of recombination
      maps within a 50 kilobase (kb) region, about 700 kb from the 4p telomere. Based
      on the extremely low HD mutation rate and significantly decreased recombination
      in the distal region of 4p, we hypothesize a direct link between the site of the
      recombination and HD in this patient.

PMID- 1345173
TI  - Cloning of the alpha-adducin gene from the Huntington's disease candidate region
      of chromosome 4 by exon amplification.
AB  - We have applied the technique of exon amplification to the isolation of genes
      from the chromosome 4p16.3 Huntington's disease (HD) candidate region. Exons
      recovered from cosmid Y24 identified cDNA clones corresponding to the alpha
      subunit of adducin, a calmodulin-binding protein that is thought to promote
      assembly of spectrin-actin complexes in the formation of the membrane
      cytoskeleton, alpha-adducin is widely expressed and, at least in brain, is
      encoded by alternatively spliced mRNAs. The alpha-adducin gene maps immediately
      telomeric to D4S95, in a region likely to contain the HD defect, and must be
      scrutinized to establish whether it is the site of the HD mutation.

PMID- 1345174
TI  - A homozygous stop codon in the lysyl hydroxylase gene in two siblings with Ehlers
      Danlos syndrome type VI.
AB  - Ehlers-Danlos syndrome (EDS) is characterized by joint hypermobility, alterations
      in the skin and additional signs of connective tissue involvement. EDS type VI
      was the first connective tissue disorder for which a specific defect in collagen
      metabolism was identified, namely a deficiency of lysyl hydroxylase activity. We
      now report a homozygous single basepair substitution converting the CGA codon
      (Arg319) to a TGA termination codon in two siblings with EDS type VI. The healthy
      parents, who are first cousins, and two of the three healthy siblings of the
      patients are heterozygous. The mutation leads to an almost complete absence of
      lysyl hydroxylase activity in extracts derived from fibroblasts of the patients.

PMID- 1345175
TI  - Genomic structure, evolutionary conservation and aniridia mutations in the human
      PAX6 gene.
AB  - Aniridia is a semidominant disorder in which development of the iris, lens,
      cornea and retina is disturbed. The mouse mutation Small eye (Sey), which has
      been proposed as a model for aniridia, results from defects in Pax-6, a gene
      containing paired-box and homeobox motifs that is specifically expressed in the
      developing eye and brain. To test the role of PAX6 in aniridia, we isolated human
      cDNA clones and determined the intron-exon structure of this gene. PAX6 spans 22
      kilobases and is divided into 14 exons. Analysis of DNA from 10 unrelated
      aniridia patients revealed intragenic mutations in three familial and one
      sporadic case. These findings indicate that the human aniridia and murine Small
      eye phenotypes arise from homologous defects in PAX6.

PMID- 1345176
TI  - Designing microbes for release into the environment.
AB  - After 20 years in which gene technology has become an important part of modern
      biotechnology we have seen very beneficial applications of the new techniques in
      the pharmaceutical industry. We are now entering a second phase involving the
      deliberate release of genetically engineered organisms into the environment. This
      next step causes concern because of a low level of predictability of their
      possible effects. While the risk assessment of microbial release is far from
      easy, the strain designers also face problems concerning optimization of
      performance of the organisms. The two groups of actors in this new development-
      the risk assessors and the strain designers--need the same platform of
      understanding from the field of microbial ecology, and a number of specific areas
      which may now be approached by modern technology deserve particular attention. An
      increased understanding of the activities of microbes in the environment will
      also allow construction of more predictable, and therefore safer, strains.
      Biological containment and molecular microbial ecology are two sides of the same
      coin in the context of release of genetically engineered microorganisms.

PMID- 1345177
TI  - Optical and dynamical investigations of fractal clusters.
AB  - The characterisation of particle shape has been an active research area and
      source of contention for over fifty years. In this paper we have reviewed the
      concept of fractal theory and its application to various aspects of industrial
      processes has been demonstrated. The application to environmental aerosols,
      especially those formed by combustion, has received much attention due to the
      increasing awareness of the global impact of aerosols on climate. Fractal
      analysis is a convenient framework for the description of complex morphologies
      and other dynamical parameters.

PMID- 1345178
TI  - Brain-gut relationships: gastric mucosal defense is also important.
AB  - Growing recognition that there exists a functionally important brain-gut axis has
      prompted several research groups to examine more closely the role of central
      nervous system factors in gastric mucosal injury. Less attention has been
      directed toward brain regulation of defensive factors in the gut. Toward that
      end, we have been characterizing a growing role for dopamine as an important
      mediator of gastric defense. New data suggest that dopamine, and other substances
      including many peptides as well as interleukin, act not only to reduce aggressive
      elements which promote gastric mucosal injury (gastric acid, pepsin, gastrin,
      leukotrienes) but also to augment defensive factors which retard ulcerogenesis
      (mucus, bicarbonate, prostaglandins, free radical scavenging enzymes,
      vasodilators/relaxers). Increasing attention should be directed toward the often
      neglected defensive aspect of gastric mucosal ulcerogenesis and protection.

PMID- 1345179
TI  - Stress ulcer modulation by limbic system structures.
AB  - A number of studies suggest that the telencephalic limbic system modulates stress
      ulcer development. The amygdala is assumed to connect sensory experiences,
      including stressful stimuli, with the emotional reactions and gastrointestinal
      effects normally produce. The hippocampal formation (entorhinal cortex, dentate
      gyrus, hippocampus) is part of a gating system, modulating the organism's coping
      ability. Changes in transmission in this temporal brain region are linked to
      individual differences in stress ulcer severity. Interactions among "classical"
      transmitters and several neuropeptides mediate these differences.

PMID- 1345180
TI  - Individual behavioral characteristics and extent of stress-induced gastric
      ulceration in rats.
AB  - Individual rats differ amongst themselves with respect to both behavior and the
      extent of stress-induced gastric ulceration, even though they have been treated
      identically, are from the same stock, age, etc. The relationship between behavior
      and ulcer susceptibility is of interest in its own right, and is reminiscent of
      the extensive body of literature on personality characteristics and disease risk
      in humans. In the Sprague-Dawley rat, we have found that animals react
      differentially to the introduction of new stimuli in a previously learned Lashley
      maze, and that the increase in latency is negatively related to attack frequency
      in a classic intruder test. Furthermore, we have found a negative correlation
      between attack latency in the intruder test and the amount of gastric ulceration
      induced by restraint-in-water stress. We have further found highly significant
      relationships between the responses of otherwise untreated animals to a simple
      startle test and the extent of gastric ulceration induced by restraint-in water
      stress. We believe that greater notice should be taken of the individual animal's
      behavioral profile for three reasons. First, prior behavioral screening may be a
      useful method for reducing error variance. Second, physiological and
      neuroendocrinological differences between high susceptible and low susceptible
      individuals are of interest in understanding the psychobiology of stress
      ulcerations both in animals and humans. Finally, an understanding of the etiology
      of these individual differences may cast light on links between behavior patterns
      and stress pathology.

PMID- 1345181
TI  - Esophageal mucosal protection--why do we need a special approach?
AB  - The epidemiology and natural history of reflux induced peptic esophageal diseases
      remain incompletely understood. That is why it is easy to explain that the
      traditional therapeutic efforts were mostly restricted to the use of acid
      reducing or neutralizing drogs. The author tries to survey--mainly on theoretical
      bases--a new approach of the maintenance treatment of peptic esophagitis and
      consequential columnar metaplasia. The mechanism of the esophageal antireflux
      barrier is composed by the (a) lower esophageal sphincter tone, (b) upper
      esophageal sphincter tone, (c) esophageal acid clearance and (d) esophageal
      epithelial resistance. The data of a 100-patient-group of gastroesophageal reflux
      disease cases were retrospectively evaluated principally considering the efficacy
      of antisecretory treatment relating to the accompanying diseases, recurrence of
      symptoms and prevention the development of Barrett's columnar lined esophagus and
      Barrett's ulceration. The decrease of exposure by damaging factors is an
      essential criterion of antisecretory therapy, having several disadvantages. Based
      only to logically well established arguments the author believes that
      gastroesophageal reflux disease and consecutive conditions might be an ideal
      model for studying and introducing esophageal cyto (-mucosal, -tissue)
      protection, considering that in the esophagus--in contradiction to the stomach-
      the cell and tissue injury, induced by several pathogenic agents, does not
      develop rapidly, and when the organ damage develops gradually, interventions may
      be possible to protect esophageal cell and the mucosa directly.

PMID- 1345182
TI  - A review of spontaneous ulcer disease in domestic animals: chickens, cattle,
      horses, and swine.
AB  - The human species is perhaps unique for its high incidence of spontaneous,
      chronic ulcer of the glandular mucosa of the stomach and duodenum. Nevertheless,
      spontaneous ulcers, usually of the stomach, commonly occur in many domestic
      animals. Some of these lesions are chronic and they may occur in either the
      glandular or squamous-lined regions of the stomach. As with the human disease(s)
      the pathogenesis in domestic animals is multifactorial, poorly understood, and
      variable between and within species. Some parallelisms exist in aggressive and
      defensive factors, but parasitic factors, via gastrinemia, and a histaminic
      factor via diet may occur in some animal ulcers. Underlying environmental
      stresses, of debated importance with the human disease but of proven importance
      in several rat ulcer models, may play a key role in some spontaneous gastric
      ulcer situations in swine and cattle. This is manifest in crowding and
      transporting situations. Seasonal, age, and weaning factors also alter the
      incidence of ulcer in cattle. Psychologic/environmental stress-related factors,
      as well as drug and physiologic stress factors appear to upset the balance in the
      horse between resistance and aggressive mucosal factors. Dietary factors which
      are highly important in ulcer disease in swine and chickens, have not yet been
      incriminated in spontaneous, equine ulcer disease. More investigation of the
      pathogenesis of domestic animal ulcers will prove useful for both human and
      veterinary medicine in terms of a) elucidating pathogenetic mechanisms for all
      species, b) may provide new animal models for study, and c) may enhance
      prevention of such lesions in domestic animals for economic and humanitarian
      reasons.

PMID- 1345183
TI  - Subcellular localization of prostaglandin E2 receptors in the gastric mucosa.
AB  - Gastric mucosal PG E2 receptors are the common antisecretory working point of all
      prostanoid types and may also be involved in "protective" effects. We
      investigated the subcellular localization of these receptors, as measured by
      displaceable 3H-PG E2 binding, and identified different organelles by monitoring
      the activities of specific marker enzymes. Porcine mucosal homogenates were
      subdivided by differential centrifugation into fractions P1 (1000 x g), P2
      (20,000 x g), P3 (300,000 x g) and the supernatant S1. P3 was further
      fractionated over a series of sucrose step gradients. Mitochondria and lysosomes
      were enriched in P2 (maximum specific activities of cytochrome-c-oxidase of beta
      glucosidase, beta-glucuronidase, beta-galactosidase, respectively). Plasma
      membranes (alkaline phosphatase, gamma-glutamyl-transpeptidase, 5-nucleotidase),
      tubulovesicles (H+/K(+)-ATPase) and rough endoplasmic reticulum (NADPH-cytochrome
      c-reductase) were mainly found in P3, which also contained the majority of 3H-PG
      E2 binding sites. In contrast, prostanoid binding was barely detectable in S1.
      Density fractionation of P3 revealed that 3H-PG E2 binding sites shared a similar
      sedimentation profile with plasma membranes and tubulovesicular markers. No or
      negative correlation was found with lysosomes, rough endoplasmic reticulum and
      mitochondria. We conclude that mucosal PG E2 receptors are predominantly located
      at the cell surface. This supports the view that prostanoids inhibit gastric
      secretion through membrane receptors, but gives no clue for intracellular
      "protective" working points.

PMID- 1345185
TI  - 5-Hydroxytryptamine3-receptor blockade protects against gastric mucosal damage in
      rats.
AB  - Ondansetron, a specific 5-hydroxytryptamine3 (5-HT3)-blocker, injected s.c.
      (0.038, 0.075, 0.15 or 0.3 mg/kg) every 12 h with the fourth dose given 0.5 h
      before restraint at 4 degrees C (stress) or oral administration (p.o.) of 1 ml
      80% ethanol, dose-dependently prevented gastric mucosal damage in female Sprague
      Dawley rats (160-180 g); the animals were killed 2 or 1 h after stress or ethanol
      p.o., respectively. A similar pretreatment regimen with cyproheptadine (0.1, 0.25
      or 0.5 mg/kg) or ketanserin (15, 30, or 75 micrograms/kg), both being 5HT2
      receptor antagonists, also dose-dependently lowered the severity of stress- or
      ethanol-induced mucosal lesions. Only the higher doses of phenobarbitone (25 or
      50 mg/kg given s.c. in a single dose 0.5 h beforehand) inhibited stress-induced
      gastric ulcers; however, even the lowest non-antinuclear dose (12.5 mg/kg),
      effectively produced CNS depression. These preliminary findings suggest that 5HT3
      receptor blockade not only can antagonise stress- or ethanol-evoked gastric
      mucosal damage, but also may act through a peripheral mechanism.

PMID- 1345184
TI  - Adenosine: a novel ulcer modulator in stomachs.
AB  - Adenosine has been demonstrated for its actions on gastric secretion and stress
      induced gastric ulceration in animals. We examined the pharmacological actions of
      adenosine on ethanol-evoked gastric lesions and gastric mucosal blood flow (GMBF)
      in rats, because both of them are closely related. Adenosine pretreatment, in
      dose of 7.5 mg/kg increased GMBF and protected against ethanol-evoked gastric
      lesion formation. However, this antiulcer action was followed by an aggravation
      of gastric lesions and reduction in GMBF. We further investigated whether these
      actions could act through the adenosine A1 or A2 receptors, therefore L
      phenylisopropyladenosine (L-PIA) or N-ethylcarboxamidoadenosine (NECA), the
      adenosine A1 or A2 receptor agonists, respectively, were used. The drugs given in
      doses of 10 or 50 micrograms/kg for L-PIA and 1 or 5 micrograms/kg for NECA, dose
      dependently inhibited GMBF and potentiated ethanol-induced gastric damage. When
      the two drugs were given together to animals, they did not further aggravate the
      severity of ulceration and reduction of GMBF. These findings indicate that the
      antiulcer action of adenosine is not mediated via the adenosine A1 and A2
      receptors but if acts through different adenosine receptor subtypes. It was
      because the lesion worsening effects of adenosine at the second stage of the
      biphasic responses were similar to the actions of L-PIA and NECA, the ulcer
      potentiating effect is probably acting through adenosine A1 and A2 receptors in
      anaesthetised rats.

PMID- 1345186
TI  - Role of mucus in mucosal protection through ethanol and pepsin damage models.
AB  - Gastrointestinal mucus is considered an important part of the mucosal defence
      mechanism against endogenous aggressors such as acid and pepsin. The mucus gel
      layer, adherent to the mucosal surface creates a diffusion barrier to luminal
      pepsin, thus protecting the underlying epithelium from the digestion by pepsin.
      The mucolytic pepsin will, however, digest the mucus at its luminal surface, but
      that lost is normally balanced by secretion of new mucus. This dynamic balance is
      disrupted when the mucus is exposed to excess pepsin, which causes focal
      haemorrhagic damage by progressively hydrolyzing the adherent mucus. The adherent
      mucus gel layer cannot contribute to the protection against exogen damaging
      agents such as ethanol and nonsteroidal anti-inflammatory drugs, as these
      compounds easily penetrate the mucus barrier causing, at high concentration,
      epithelial exfoliation. This study describes the basic properties and
      characteristics of gastric mucus and compares the pepsin-induced damage with the
      ethanol damage model.

PMID- 1345187
TI  - Is acute surgical vagotomy an aggressor to gastric mucosa in pylorus ligated rats
      with and without indomethacin treatment?
AB  - Previously it was proved that intact vagal nerve is basically necessary for the
      development of gastric cytoprotection. The aims of this study were to receive
      further data about the role of vagal nerve in the development of gastric mucosal
      damage. The observations were carried out on Sprague-Dawley rats. Acute bilateral
      surgical vagotomy was done with pylorus ligation and/or indomethacin (IND)
      treatment (20 mg/kg, sc.) at the time of operation. The animals were sacrificed 4
      h after the operation. The number, the severity (semiquantitative method), the
      mean size and summed surface (computer assisted quantitative method) of gastric
      mucosal damage, the H+ output and the mucosal PGE2 level were determined. It has
      been found that 1) the ASV itself (without IND or pylorus ligation) provoked
      gastric mucosal damage, which was more severe than in the pylorus ligated animals
      at 4 h; 2) IND was able to reduce the summed surface of mucosal damage after ASV;
      3) ASV aggravated the gastric mucosal damage in pylorus ligated animals in spite
      of the decreased H+ output; 4) the PGE2 level was lower in vagotomized and
      vagotomized+pylorus ligated animals then in the control group, and the IND did
      not cause further decrease in its level after ASV. It has been concluded that the
      balance between aggressive and defensive factors of gastric mucosa was shifted to
      the aggressive side in surgically vagotomized animals.

PMID- 1345188
TI  - Effect of acute surgical vagotomy on the mucosal content of 6-keto-PGF1 alpha,
      PGE2 and glutathione after intragastric 96% ethanol treatment in rats.
AB  - It has been observed earlier that gastric cytoprotection produced by PGI2, beta
      carotene, small doses of atropine or cimetidine has failed in surgically
      vagotomized rats. This phenomenon may be in connection with endogenous
      prostaglandins (PGs) and glutathione (GSH) level of the gastric mucosa. The aims
      of the study were to evaluate the effect of vagus nerve on the gastric mucosal 6
      keto-PGF1 alpha, PGE2 and glutathione after intragastric 96% ethanol (ETOH)
      treatment. The observations were carried out on CFY rats. The gastric mucosal
      damage was produced by intragastric administration of 1 ml 96% ETOH. Acute
      bilateral surgical vagotomy (ASV) was carried out 30 min prior to ETOH
      application. The animals were sacrificed 1, 5, 15 or 60 min after ETOH
      installation. The number and the severity of gastric mucosal lesions were noted
      and 6-keto-PGF1 alpha, PGE2 an GSH contents of gastric mucosa were measured. It
      has been found that: 1. the number and the severity of gastric mucosal lesions
      were increased after ASV compared to those with intact vagal nerve, 2. 96% ETOH
      treatment increased both the gastric mucosal PGs and GSH levels, 3. 6-keto-PGF1
      alpha peaked at 5 min PGE2 and GSH peaked at 15 min after ETOH treatment, 4. ASV
      decreased the gastric mucosal PGs content and delayed the peaks of PGE2 and GSH.
      It has been concluded that the decreased content of PGs and the delayed GSH
      increase may play a pathological role in the failure of gastric cytoprotection of
      rats after ASV.

PMID- 1345189
TI  - Correlation between the cytoprotective effect of beta-carotene and its gastric
      mucosal level in indomethacin (IND) treated rats with or without acute surgical
      vagotomy.
AB  - As to earlier observations that beta-carotene prevents the development of gastric
      mucosal injury produced by different noxious agent, however, its cytoprotective
      effect can be abolished by acute surgical vagotomy. The aim of this study was to
      evaluate the possible correlation between the gastric mucosal cytoprotective
      effect of beta-carotene and its gastric mucosal level in rats treated with IND.
      The gastric mucosal damage was produced by the administration of IND (20 mg/kg
      s.c.). The instillation of beta-carotene and acute surgical vagotomy (ASV) or
      SHAM operation were carried out 30 min before IND treatment. The rats were
      sacrificed 4 h after IND application, and the number and severity of gastric
      mucosal erosions were noted. The blood rats was collected quantitatively, the
      liver and the gastric mucosa were removed, and the beta-carotene and vitamin A
      level of the gastric mucosa, serum and liver were measured with HPLC. It was
      found that: 1. Beta-carotene induced gastric cytoprotection in SHAM-operated rats
      treated with IND but its effect disappeared after ASV. 2. Although the beta
      carotene level of the gastric mucosa increased its concentration was not elevated
      in the serum of intact and vagotomized animals either. 3. Vitamin A Formation was
      not detected in the liver of animals with or without ASV. It was concluded that
      the lack of intake of beta-carotene into the gastric mucosa can not play
      etiologic role in the failure of gastric cytoprotection of rats with acute
      bilateral surgical vagotomy.

PMID- 1345190
TI  - Acute and chronic surgical vagotomy (SV) and gastric mucosal vascular
      permeability in ethanol treated rats.
AB  - The role of vagus nerve was studied in the development of gastric mucosal damage
      induced by ethanol (ETOH). The investigations were carried out on Sprague-Dawley
      rats. The gastric mucosal damage was produced by i.g. administration of 1 ml 96%
      ETOH. Acute surgical vagotomy (ASV) was carried out 30 min, chronic surgical
      vagotomy (CSV) 14 days before the ETOH application. The animals were sacrificed
      at 0, 1, 5, 15, 60 min after ETOH. Evans blue (EB) (1 mg/100 g) was given i.v. 15
      min before autopsy. The number and severity of lesions the EB accumulation of the
      gastric juice and gastric mucosa were noted. It was found, that: 1. The vascular
      permeability increased after ETOH treatment at an early state (within 1-5 min) in
      association to the macroscopic appearance of erosions. 2. The number and
      extension of lesions, the EB concentrations in gastric juice and gastric mucosa
      were significantly higher both after ASV and CSV. 3. Surgical vagotomy alone did
      not increase the vascular permeability. 4. No significant ulcer formation was
      observed in vagotomized rats without ETOH treatment. It was concluded, that 1.
      Both ASV and CSV enhanced the development of gastric mucosal injury induced by
      ethanol. 2. Neither acute nor chronic surgical vagotomy exerted an effect of the
      development of mucosal injury and vascular permeability without the application
      of the noxious agent. 3. The further increase of enhanced vascular permeability
      by vagotomy probably has an etiologic role in the aggravating effect of ASV and
      CSV on the development of chemical-induced lesions.

PMID- 1345191
TI  - Synthesis and gastroprotective activity of 4H-pyrido[1,2-a]pyrimidin-4-ones.
AB  - The cytoprotective effect of different types of 4h-pyrido[1,2-a]pyrimidin-4-one
      derivatives was investigated. Short synthesis of the investigated compounds was
      depicted. The gastroprotective effect was determined against acidified ethanol
      induced mucosal lesions in rats. The most effective compounds belong to
      unsaturated 4-oxo-4h-pyrido[1,2-a]pyrimidine-3-carboxamide derivatives, and the
      most active one contains a methyl group in position 6 and a cyclopentyl group on
      the nitrogen of the carboxamide group. Further pharmacological, biochemical and
      clinical studies may justify, that the representative of this type of compounds
      may be useful as prophylactic agents against gastric damage caused by non
      steroidal antiinflammatory agents.

PMID- 1345192
TI  - Mechanisms of NSAID-induced ulcerogenesis: structural properties of drugs, focus
      on the microvascular factors, and novel approaches for gastro-intestinal
      protection.
AB  - The multifactorial ulcer-producing actions of non-steroidal anti-inflammatory
      drugs (NSAIDs) are briefly reviewed and the main actions highlighted as the focus
      for potential strategies for reducing the ulcerogenic effects of these drugs.
      While some clinical benefits are evident from long-term clinical studies from
      application of PG analogues (misoprostol) and H+/K(+)-ATP-ase inhibitors
      (omeprazole) these are, ultimately, expensive approaches. Chemical structural
      properties of the NSAIDs underlying differences in their ulcerogenicity are
      analyzed with the objective of establishing the reasons for the low
      ulcerogenicity of some of these drugs (e.g. azapropazone). These studies serve as
      a basis for developing less gastrotoxic drugs in the future. In the studies we
      have undertaken analysis of the benefits of micronutrients and of modulating
      eicosanoid metabolism have been considered. The results of some clinical trials
      with micronutrients have proven encouraging. These and other approaches and
      pitfalls reported give further encouragement to explore the mechanisms of the
      protective effects of these latter agents and serve as a basis for future
      developments.

PMID- 1345193
TI  - The mechanism of cytoprotective effect of CHINOIN-127.
AB  - According earlier, investigations nitrogen bridgehead compounds make a
      representative group of non-prostaglandin type gastroprotective agents. One
      member of this group is CHINOIN-127 (1,6-dimethyl-4-oxo-1, 6, 7, 8, 9, 9a
      hexahydro-4H-pyrido-(1, 2a)-pyrimidine-3-carbox-amide). CHINOIN-127 is a potent
      non-narcotic analgesic and antiinflammatory agent and has a remarkable protective
      effect on indomethacin induced ulcer (ED50 = 25 mg/kg p.o.) and on acidified
      ethanol induced ulcer (ED50 = 26 mg/kg p.o.). In this study we examined the
      mechanism of action of cytoprotective effect of this drug and we made a
      comparison between the cytoprotective effect of 20% ethanol and 25 mg/kg CHINOIN
      127. In the gastric mucosa of control rats we observed a balance between TxA2 and
      PGI2 (PGI2/TxA2 = 3.8) and between the cytoprotective prostaglandins (PGI2 and
      PGE2) and ulcerogen eicosanoids (TxA2 and leukotrienes) (PGI2 + PGE2/TxA2 + LTs =
      3.9). 100% ethanol treatment causes disintegration of this balance, shifting the
      synthesis towards the ulcerogen eicosanoids production. CHINOIN-127 and 20%
      ethanol pretreatment improves the deranged balance between cytoprotective
      prostaglandins and ulcerogen eicosanoids. Our results demonstrate that CHINOIN
      127 and 20% ethanol have a similar mechanism of cytoprotective action on ethanol
      induced ulcer in rats.

PMID- 1345194
TI  - Are all "cytoprotective" drugs gastroprotective?
AB  - The effect of three--structurally different--groups of compounds was compared
      against gastric mucosal damages induced by ethanol or prostaglandin (PG)
      synthesis inhibitors, as well as against carrageenan-induced inflammation. All
      the compounds studied--SH-compounds (cysteamine, 2,3-dimercaptosuccinic acid, D,L
      penicillamine), SH-blocking N-ethylmaleimide (NEM) and morphine-exerted dose
      dependent inhibition on carrageenan edema test and against ethanol-induced
      gastric damage. Mucosal lesions induced by PG synthesis inhibitors (indomethacin
      20 mg/kg, naproxen 75 mg/kg, piroxicam 60 mg/kg) were inhibited by drugs studied
      when the compounds were given before the damaging agents. However, when the drugs
      were injected 1 h after the inhibitors of PG synthesis opposite actions were
      observed; SH-compounds exerted protective, while NEM (2 mg/kg p.o.) and morphine
      (5 mg/kg p.o.) aggravating action. The results suggest that: 1. SH-compounds
      might have therapeutic importance in the treatment of gastric damage induced by
      prostaglandin synthesis inhibitors. 2. Reconsideration of the use of the term
      "cytoprotection" is necessary, since "cytoprotective" agents may aggravate
      mucosal damage in other ulcer model.

PMID- 1345195
TI  - The antineoplastic drugs dose dependently inhibit the healing of subacute gastric
      ulcer produced by punching in rats.
AB  - The aim of present study was to investigate the effects of some antineoplastic
      drugs on the healing process of subacute gastric ulcer, produced by punching, in
      rats. We determined the doses which inhibit the healing rate by 50%. Our results
      confirm the general observation that present applied anticancer drugs cannot
      distinguish between normal and tumor cell proliferation. The ID50 values of
      tested drugs strongly correlate with human doses.

PMID- 1345196
TI  - Selenium in the blood of patients with colorectal cancer and neoplastic polyp.
AB  - Samples of whole blood were obtained from 51 patients with newly diagnosed
      colorectal cancer as well as from 76 patients with neoplastic colorectal polyp,
      and from 30 healthy blood bank donors. Selenium was determined by the
      fluorimetric method. Significantly decreased selenium concentrations of blood
      samples from patients with colorectal cancer and villous adenoma were found.
      There was not any correlation between the blood selenium levels of patients with
      adenomatous polyp and the severity of dysplasia in removed polyps. The lowest
      mean selenium level in patients with villous adenoma indicates that selenium
      deficiency may be an important factor in the development of colorectal cancer
      arising from villous adenomas.

PMID- 1345197
TI  - Measurement of non-steroid antiinflammatory drugs induced gastric microbleeding.
AB  - The damage of the mucous membranes in the gastrointestinal tract caused by non
      steroid antiinflammatory drugs are well known. The gastrointestinal microbleeding
      was measured by the method of Fischer and Hunt before and after the intake of
      indomethacin (4 x 25 mg), naproxen-sodium (4 x 275 mg), diclofenac (3 x 50 mg)
      and azapropazone (2 x 600 mg). In the indomethacin group microbleeding increased
      from 0.91 +/- 0.12 ml/24 h to 7.30 +/- 1.20 ml/h. In the naproxen-sodium group
      from 1.22 +/- 0.16 ml/24 h to 3.56 +/- 0.40 ml/24 h, in the diclofenac group from
      0.86 +/- 0.14 ml/24 h to 3.18 +/- 0.28 ml/24 h, in azapropazone group from 0.92
      +/- 0.18 ml/24 h to 2.50 +/- 0.20 ml/24 h, respectively. All non-steroid
      antiinflammatory drugs increased the gastric microbleeding, however, there were
      considerable differences in the degree of enhancement. This can be explained by
      the different inhibitory activities of the drugs on the cyclooxygenase enzyme
      activity.

PMID- 1345198
TI  - Influence of sex hormones on ethanol-induced gastric haemorrhagic erosions in
      rats.
AB  - The role of sex hormones in the pathogenesis of ethanol-induced gastric erosions
      was investigated following the recent observation that ethanol generates more
      severe gastric damage in male rats. Female and male Wistar rats aged 110 +/- 6
      days were used. Intact female, ovariectomized female, intact male,
      orchidectomized male and cyproterone acetate-pretreated (this compound a
      testosterone antagonist) male rats were investigated. 1 ml of 75% ethanol was
      used to induce gastric lesions. The extent of the erosions was determined
      planimetrically 60 min after ethanol administration. The plasma testosterone and
      17-beta-oestradiol levels were checked by radioimmunoassay (RIA) in
      gonadectomized rats. Ethanol generates more severe lesions in male rats.
      Orchidectomy and cyproterone acetate treatment each reduced the extent of ethanol
      induced gastric erosions in male rats. Ovariectomy had no effect in this model.
      The plasma testosterone and 17-beta-oestradiol levels were significantly reduced
      after gonadectomy. It is concluded that endogenous testosterone plays an
      aggressive role in the pathogenesis of ethanol-induced gastric erosions in rats.

PMID- 1345199
TI  - The effects of local hyperthermia on the morphology of the small bowel.
AB  - Intestinal lesions were produced experimentally by heating the eventrated loop of
      the small intestine of Wistar rats in 44 degrees C 0.9% saline 20 minutes.
      Luminal haemorrhage and elevation of the potassium concentration in the wash-out
      fluid were registered from the fifth minute of the experiment. In the sediment of
      the wash-out fluid erythrocytes, degenerated and necrotic epithelial cell
      clusters were found. Histologically the mildest lesions were subnuclear
      vacuolization of the epithelial cells and stromal oedema of the villi. In the
      medium-degree lesion subepithelial cleft formation, desquamation of the
      epithelial cells and denudation of the villi occurred. The fully developed lesion
      was characterized by the destruction of the villi intestinalis and haemorrhage.
      This lesion produced by local heating differs from the intestinal lesions of the
      rats exposed to high environmental temperature basically in the haemorrhagical
      nature of the former lesion.

PMID- 1345200
TI  - Pathogenesis and management of alcoholic liver injury.
AB  - The present paper is devoted to overview the basic concepts of ethanol-induced
      hepatic injury and therapeutic modalities by which alcoholic liver disease can be
      alleviated. The role of alcohol dehydrogenase of both hepatic and gastric origin
      as well as the importance of the number one metabolite acetaldehyde are
      discussed, furthermore the effects of microsomal ethanol oxidizing system are
      also described. The features of the major clinicopathological consequences of
      alcohol abuse fatty liver, alcoholic hepatitis are briefly outlined, and the
      basic pathogenetic mechanisms that lead to cirrhosis--cell necrosis, regeneration
      and fibroplasia--are shown. The understanding of the pathophysiology of alcohol
      induced liver injury may improve the therapy with drugs and nutritional factors,
      and allow successful prevention through the early recognition of heavy drinkers
      before their social or medical disintegration. In the management of alcoholic
      liver diseases, among the true hepatoprotective agents a naturally occurring
      flavonoid silymarin and an active methyl-donor metabolite S-adenosyl-L-methionine
      seem to be promising. An antifibrotic treatment with colchicine might also be of
      importance. Further prospective, well-designed, controlled clinical trials are
      still warranted to evaluate real efficacy of these drugs. The hepatic
      consequences of alcohol abuse may be treatable, however, prevention would be the
      true resolution of the major global health problem of alcoholism.

PMID- 1345201
TI  - Role of free-radical reactions in liver diseases.
AB  - Role of free-radical reactions is most significant in toxic liver injuries. Two
      traditional groups of liver injuries induced by drugs and chemicals are
      distinguished, 1. direct toxic type and 2. idiosyncratic type. Liver injury of
      direct toxic type is generally developed following toxin exposure, it is dose
      dependent, incubation period is short, and the injury often affects other organs
      (e.g. kidney). Direct toxins frequently cause typical zonal necrosis usually
      without concomitant signs of hypersensitivity. It is typical of idiosyncratic
      reaction that it appears only in a shorter period of exposure, it cannot be
      predicted, it is not dose-dependent, its incubation period varies and sometimes
      (in one-fourth of cases) it is accompanied by extrahepatic symptoms of
      hypersensitivity (fever, leukocytosis, eosinophilia, rashes), its morphologic
      picture shows great variety. A part of direct toxins is toxic itself, in the
      other part the basic compound is not toxic but it changes into toxic metabolites
      in the liver. Liver is well-protected against free-radicals developing in the
      organism: it is one of our best antioxidant supplied organs. It is probably due
      to the one of the important tasks of liver, namely detoxication of drugs,
      chemicals and toxic materials, with subsequent release of free-radicals. It is
      proved by the fact that in normal bile peroxidized lipids produced by free
      radical chain reactions can also be detected. The pathologic free-radical
      reactions and one of their sequelae, peroxidation of lipids (LPO) do not
      necessarily cause cell and tissue damage. Antioxidant protection of cells and
      tissues is able to prevent free-radical injury and it enables, that the already
      developed damages become reversible. According to recent investigations, the
      lipid peroxidation, caused by free-radical reactions, or covalent binding of
      radical products to biomolecules does not lead directly to cellular destruction,
      only via further reactions. Such intermediary steps can be the phospholipase A2
      activation, accumulation of lysophosphatides, poly-ADP-ribose polymerase repair
      enzyme activation, following oxidative damage of DNA, with subsequent NAD and ATP
      depletion. Its significance may be that the irreversible cellular and tissue
      damage can be prevented perhaps not only by administration of antioxidants, but
      also by compounds (e.g. phospholipase A2 inhibitors) affecting the above
      mentioned biochemical mechanisms.

PMID- 1345202
TI  - Cytoprotection in the nineties: experience with ursodeoxycholic acid and
      silymarin in chronic liver disease.
AB  - The authors report their experience in the use of ursodeoxycholic acid and
      silymarin in patients with active cirrhosis of different aetiology. Both drugs
      seemed safe and ameliorated the biochemical indices of cytolysis; however, the
      former did not appear to be effective when hepatic dysfunction was associated to
      hepatitis C infection. The residual functional liver mass, as assessed by
      quantitative liver function tests, was not affected by either cytoprotective
      agent.

PMID- 1345203
TI  - Clinical evidence of hepatoprotection induced by ursodeoxycholic acid.
AB  - Ursodeoxycholic-acid (UDCA) was introduced to the clinical practice as an
      effective agent for the dissolution of gallstones. The efficacy of UDCA was
      proved recently in the treatment of patients with chronic cholestatic liver
      disease. We demonstrate the hepatoprotective effect of UDCA in a patient with
      chronic cholestatic liver disease. A sixty-nine years old male patient was
      admitted to our department with severe jaundice. The laboratory and radiologic
      examinations revealed significant cholestasis without any morphological
      alterations. Among the serological tests the anti-HCV antibody was positive.
      Based on these findings and anamnestic data (no blood transfusion and/or
      operation), sporadic chronic C virus hepatitis was assumed with dominant
      cholestasis. The corticosteroid therapy even in high doses was ineffective, the
      liver function parameters worsened. Later UDCA (Ursofalk, Falk Pharma) was given
      at a dose of 250 mg three times daily. Clinical improvement was seen after the
      first week of UDCA treatment. The patient's complaints relieved parallel with
      decrease of serum bilirubin, gamma-glutamyl transferase and transaminase levels.
      These parameters showed further decrease during the treatment.

PMID- 1345204
TI  - The effect of silibinin (Legalon) on the the free radical scavenger mechanisms of
      human erythrocytes in vitro.
AB  - The effect of Legalon was investigated parallel with that of Adriblastina
      (doxorubicin) and paracetamol on some parameters characterizing the free radical
      scavenger mechanisms of human erythrocytes in vitro and on the time of acid
      hemolysis performed in aggregometer. Observations suggest that Adriblastina
      enhances the lipid peroxidation of the membrane of red blood cells, while
      paracetamol causes significant depletion of intracellular glutathione level, thus
      decreasing the free radical eliminating capacity of the glutathione peroxidase
      system. Legalon on the other hand, is able to increase the activity of both
      superoxide dismutase and glutathione peroxidase, which may explain the protective
      effect of the drug against free radicals and also the stabilizing effect on the
      red blood cell membrane, shown by the increase of the time of full haemolysis.

PMID- 1345205
TI  - Endogenous scavenger levels (vitamin E and A) of patients with chronic alcoholic
      liver disease under different environmental conditions.
AB  - Serum level of endogenous scavengers (E and A vitamin) was studied in groups of
      patients with various chronic alcoholic liver diseases and in a healthy control
      group on polluted and non-polluted areas. Vitamin levels in patients with chronic
      liver disease are diminished in comparison to the healthy in general, but mainly
      in the cirrhotic group. Diminution of vitamin E levels was observed in earlier
      phase of liver disease than that of vitamin A levels. Patients and healthy
      control on polluted area showed more expressed diminution of vitamin levels than
      the same groups on non-polluted area. Free radical parameter (RBC diene conjugate
      content) and characteristic alcoholic parameters (serum GOT, gamma-GT,
      cholesterol level and liver GOT, gamma-GT content in biopsy specimen) were used
      to explain the differences between the same investigated groups on polluted and
      non-polluted areas. As conclusion can be supposed that industrial pollution of
      environment has a worsening effect in diseases with free radical mechanism.

PMID- 1345206
TI  - ATP breakdown and resynthesis in the development of gastrointestinal mucosal
      damage and its prevention in animals and human (an overview of 25 years ulcer
      research studies).
AB  - The changes in membrane-bound ATP systems (breakdown and resynthesis) were
      analyzed in different experimental ulcer models (such as ETOH, HCl, NaOH, 25%
      NaCl-induced, pyloric ligated + epinephrine treated, stress, reserpine treated,
      indomethacin treated rat models) and chronic antral, duodenal and jejunal ulcers
      in patients. The energy system parameters (adenosine triphosphate (ATP),
      adenosine diphosphate (ADP), adenosine monophosphate (AMP), cyclic AMP (cAMP),
      lactate) were measured from different sites of gastrointestinal mucosa, and
      values of ATP/ADP, adenylate pool (ATP + ADP + AMP) and energy charge ((ATP + 0.5
      ADP)/(ATP + ADP + AMP)) were calculated. The biochemical measurements were done
      at different times during the development of gastrointestinal mucosal lesions,
      without and with application of different drugs (PGI2, atropine, cimetidine) and
      bilateral surgical vagotomy. The aims of our present paper were: 1.) To summarize
      the main directions of ATP breakdown during the development of gastrointestinal
      lesions or ulcers in different experimental models and human beings: 2.) To
      summarize the biochemical steps of defense of gastrointestinal mucosa against
      chemicals, drugs or unknown pathogenic factors; 3.) To analyze the importance of
      membrane-bound ATP-dependent energy systems in order to understand the mucosal
      lesions and their prevention; 4.) To evaluate the real values of changes in these
      parameters from the point of view of ulcerogenesis and its prevention; 5.) To
      find some correlation between the energy parameters during mucosal damage and its
      prevention: 6.) To understand better the types of tissue reactions (metabolic)
      due to development of mucosal lesions and prevention.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1345208
TI  - Pancreatic cytoprotection: new approaches.
AB  - A brief report is given on the possible role of oxygen-derived free radicals and
      cholecystokinin in the pathogenesis of experimentally induced acute pancreatitis.
      Furthermore, use of scavengers (superoxide dismutase, catalase), CCK-receptor
      antagonists and somatostatin are discussed in the therapy of acute pancreatitis
      induced in animal models. It is suggested that both the term of direct pancreatic
      cytoprotection of the above-mentioned agents and the validity of the animal
      models used for induction of acute pancreatitis have to be reconsidered.

PMID- 1345207
TI  - Post-cholecystectomy syndrome and magnesium deficit.
AB  - The serum level of magnesium and calcium was systematically measured in patients
      with gallstones before and after cholecystectomy. It was found that 60 percent of
      the operated patients suffered of different digestive syndromes in association
      with magnesium deficiency, while 40 percent of patients had the same complaints
      in association of magnesium and calcium deficiency. When magnesium and/or
      magnesium plus calcium was supplemented these syndromes could be decreased
      significantly. In the latter case, an optimal ratio of magnesium/calcium is
      needed in the supplementary therapy.

PMID- 1345209
TI  - Gastric anti-ulcerogenic drug effect. A possible mechanism of its molecular
      basis.
AB  - During experimental gastric ulceration in rats an elevation in the mucosal
      cAMP/cGMP ratio can be encountered. The cause of this significant elevation is
      mainly (but not entirely) the dramatic fall of the cGMP level. Similar
      observations were obtained with prostacyclin application (100 micrograms/kg,
      p.o.), too. This prostaglandin derivative is well known, among others, because of
      its pronounced anti-ulcerogenic (cytoprotective) effect, too. Other substances of
      different molecular structure and properties may also exert such effect. The
      exact mechanism of action of this above-mentioned cytoprotection is still not
      completely understood. H2-receptor blocker drug cimetidine, given in such small
      dose (5 mg/kg, p.o.) which does not interfere with gastric acid secretion, also
      exerts very significant cytoprotective effect in stress (restraint)- and drug
      (indomethacin)-induced gastric ulcer models. Under cimetidine effect--together
      with a noticeable endogenous prostacyclin mobilization--the gastric mucosal
      cAMP/cGMP ratio was also strongly elevated. We conclude that this elevation in
      the mucosal cAMP/cGMP ratio might be a possible molecular basis of the gastric
      cytoprotective (anti-ulcerogenic) drugs but it needs further investigations
      whether all substances exerting cytoprotective effect, e.g. atropine,
      somatostatin, sulfhydryl drugs, etc., have the same "shifting" property or not?
      Moreover the phenomenon of the so-called "adaptive cytoprotection" can not be
      ruled out completely either, therefore this problem needs attention, too.

PMID- 1345211
TI  - Pathways, mediators and mechanisms of gastroduodenal mucosal injury.
AB  - This review provides evidence that gastroduodenal mucosal injury is a complex
      process because of the heterogeneous structure and multiple functions of the gut.
      The action of exogenous etiologic agents is usually mediated in part, or
      amplified by endogenous mediators which very often exert biphasic, i.e., damaging
      and protective effects. The pathogenetic pathways involve direct/indirect
      chemical injury, vascular damage and its consequences, and acute or chronic
      inflammatory processes following infectious, chemical or ischemic injury. The
      role of oxygen, free radicals, calcium and proteases as well as the components
      and forms of gastroduodenal injury, e.g., reversible and irreversible cell
      injury, tissue necrosis, acute and chronic inflammation are also briefly
      discussed. Only a slight or moderate direct cytoprotection was demonstrated in
      vitro using isolated, mixed rat gastric mucosal cells by the known
      gastroprotective drugs including PG and SH compounds. Thus, the terms of organo
      or gastroprotection are more descriptive then the misleading "gastric
      cytoprotection".

PMID- 1345210
TI  - The significance of the gastroprotective effect of body protection compound
      (BPC): modulation by different procedures.
AB  - To elucidate any mechanism of a body protecting effect the observed events should
      be investigated also by the way of their modulations induced by ablation of
      particular organs. For Body Protection Compound (BPC), a newly partially
      characterized gastric juice peptide, the gastroprotection has largely been
      studied in basal and modified conditions of 48 h-restraint stress. Ablations or
      sham operations have been performed before restraint as follows: 60 min vagotomy,
      24 h ovaria, testes, spleen, 48 h medulla of adrenal glands, 40 days thyroid +
      parathyroid glands. BPC (10 micrograms/kg) or saline (5 ml/kg) have been
      regularly applied (after surgery, 1 h before restraint) intraperitoneally. The
      group subjected to thyroparathyroidectomy received also once-daily BPC/saline
      treatment. A very strong gastroprotective effect in basal conditions has been
      modulated by ovariectomy and demedullation (abolishment), thyroparathyroidectomy
      (decrease), and no change occurred in case of vagotomy, splenectomy or
      orchidectomy. Sham operated rats did not differ from corresponding controls.
      Thus, seeing from point of view a wide range of organoprotective effects of BPC
      (intestinum, kidney, liver, pancreas, inflammation, diabetes mellitus, delayed
      type of hypersensitivity), the gastroprotection has been supposed a) to be of
      crucial pattern in the general concept of organo-protection and b) to be
      responsible for the mediation of the suggested "stomach stress organoprotective
      response". Therefore, the obtained modulations suggest a complex and specifical,
      sex-related action of the overall beneficial effects of BPC.

PMID- 1345212
TI  - Ethanol and the antioxidant defense in the gastrointestinal tract.
AB  - Ethanol is known to have profound actions on the gastrointestinal tract. The
      present study was undertaken to examine the effects of ethanol on some of the
      natural antioxidant defensive enzymes in the gastrointestinal tract; the
      activities of these enzymes in the liver and the brain were also measured for
      comparison with those in the gastrointestinal tract. Oral administration of
      absolute ethanol induced severe gastric mucosal lesions and also damage in the
      small intestine, however the total superoxide dismutase was unaffected in the
      tissues measured. The glucose-6-phosphate dehydrogenase activity was reduced only
      in the stomach while the total glutathione was elevated in the small intestinal
      mucosa. The catalase activities were activated in the stomach, small and large
      intestines, and brain, but not in the liver which contained the highest
      concentration of the enzyme. The present findings indicate that endogenous
      hydrogen peroxide may be an important damaging agent towards biomolecules in
      different organs and the removal of this by catalase represents an important
      defensive mechanism against ethanol toxicity.

PMID- 1345213
TI  - Hospice values, access to services, and the Medicare hospice benefit.
AB  - The Medicare benefit has been an important force in shaping the American hospice
      movement during the 1980's. Hospice reimbursement under Medicare added legitimacy
      to the movement, increased access to hospice care for some Medicare
      beneficiaries, and provided financial support to Medicare certified hospice
      programs. But the increased access for some may come at the cost of decreased
      access for others, and the price of reimbursement may be the erosion of hospice
      as a unique form of terminal care in this country. It is up to hospice
      professionals to balance the fiscal realities of providing hospice care without
      losing sight of the values and philosophies that have made hospice a "special
      kind of care."

PMID- 1345214
TI  - Determinants of lung cancer risk among cadmium-exposed workers.
AB  - Workers at a cadmium recovery plant in Globe, Colorado, showed an increased risk
      of lung cancer, which some investigators have attributed to cadmium exposure. We
      conducted a cohort mortality analysis of this work force and a case-control
      analysis of the lung cancer cases within this work force in order to assess the
      probable causes of the lung cancer excess. The Globe plant began as a lead
      smelter about 1886, switched to arsenic production in 1920, and became a cadmium
      metal production facility in 1926. Cadmium, arsenic, and cigarette smoking are
      three potential lung carcinogens found in this workplace. Industrial hygiene data
      collected from 1943 onward served as the basis for the National Institute for
      Occupational Safety and Health (NIOSH)-derived exposure algorithm that assigned
      cadmium exposure estimates to employees based on their work area in the plant and
      calendar time. Few exposure data existed for substances other than cadmium.
      Feedstock ore concentrations were used as a surrogate measure of air arsenic
      levels. The arsenic content of the fines used as feedstock prior to 1940 was
      considerably higher than that of the fines used after 1940. Smoking histories had
      been obtained previously for 45% of the workers. A case-control analysis of the
      25 cases of lung cancer known to have occurred among these workers through 1982
      was conducted using three controls per case, matched by closest data of hire and
      age at hire. Potential causal agents for lung cancer included cadmium exposure,
      cigarette smoking, and arsenic exposure. Exposure variables for each case and
      control included estimated cumulative cadmium exposure in milligram-years per
      cubic meter, cigarette smoking history, and plant arsenic exposure status at the
      time of hire. Estimated cumulative cadmium exposures of cases and controls did
      not differ overall or within the date-of-hire strata. Cases were more than eight
      times more likely to have been cigarette smokers than were controls. Lung cancer
      risk in this workplace was more closely related to the period of hire, not to the
      cumulative cadmium exposure. The period of hire appears to be a surrogate for
      arsenic exposure as related to feedstock. The measures used here seem to indicate
      that exposure to arsenic and cigarette particulates, rather than to cadmium
      particulates, may have caused the increased rate of lung cancer of these workers.

PMID- 1345215
TI  - The role of salt in hypertension.
AB  - There is considerable evidence that salt is an important cause of hypertension.
      Primitive societies who ingest little or no salt have no hypertension. Also when
      diets very low in salt such as the rice and fruit diet are given to hypertensive
      patients, the blood pressure often falls toward normal. Unfortunately, when diets
      only moderately low in sodium have been given only minor reductions in blood
      pressure occur. Salt-induced hypertension has been produced in both man and
      experimental animals. The basic cause of the hypertension is an inability of the
      kidney to excrete the increased salt. Hemodynamic changes then occur which raise
      the blood pressure and so excrete the excess salt by pressure diuresis. The
      ability to excrete salt at normal levels of blood pressure varies from one
      individual to another. Those who require a higher than normal blood pressure are
      said to be "salt-sensitive". Those who can excrete excess salt at normal levels
      of blood pressure are called "salt resistant". The difference may be due to an
      inherited defect in the kidney to excrete salt. In any event, salt sensitive
      hypertension is effectively controlled with the administration of diuretics.

PMID- 1345216
TI  - Salt and blood pressure.
AB  - Current evidence does not support the view that the claimed association between
      salt intake and blood pressure is causal. In intercultural studies it is
      impossible to distinguish between a genuinely causal relationship and a
      relationship due to the role of salt intake as a marker for different life
      styles. Physiological studies suggest that the Western intake of salt corresponds
      to a physiological set point selected when free choice is offered as the mid
      point between harmful physiological extremes. When flawed intervention studies
      are excluded there is no evidence that a moderate reduction in salt intake would
      produce a significant blood pressure fall in healthy individuals although blood
      pressure falls can be produced in some hypertensive subjects.

PMID- 1345217
TI  - Goals of antihypertensive treatment: prevention of cardiovascular events and
      prevention of organ damage.

PMID- 1345218
TI  - Haemodynamic findings and response rates to beta-blocker--and diuretic
      monotherapy in mild and moderate hypertension. A one year randomized, double
      blind study in 100 men.
AB  - In a randomized double blind study 100 men (mean age 46 (22-64) years) with mild
      to moderate hypertension were followed every 3rd month for one year. Fifty were
      randomized to atenolol 50 mg and 50 to hydrochlorothiazide 25 mg+amiloride 5 mg
      (co-amiloride) once daily. The doses were doubled at 3 or 6 months if diastolic
      blood pressure (DBP) remained > or = 95 mmHg. If DBP was > or = 95 mmHg even at 6
      or 9 months, patients were classified as non-responders, and nifedipine 20 mg
      b.i.d. was added. After one year 31/50 randomized to atenolol and 17/50
      randomized to co-amiloride had responded to monotherapy (p < 0.05). Neither
      clinical findings nor haemodynamic measurements by Doppler at baseline could
      distinguish between co-amiloride responders and non-responders. Conversely, non
      responders to atenolol as compared with atenolol responders had higher body
      weight (p = 0.02), higher systolic BP (p = 0.03), higher DBP (p = 0.009), stroke
      volume (p = 0.04), and cardiac output (p = 0.0002) combined with lower total
      systemic vascular resistance (p = 0.02). This suggests that some were apparent
      non-responders due to too low dosing of atenolol rather than true non-responders.
      Measurements of haemodynamics may be of importance in the assessment of optimal
      antihypertensive therapy according to baseline and follow-up haemodynamic
      aberrations.

PMID- 1345219
TI  - Circadian rhythm of blood pressure in patients with obstructive sleep apnea.
AB  - AIMS: The aims of this study were to examine the circadian variation in blood
      pressure (BP) in obstructive sleep apnea (OSA) and to compare this between
      normotensive and hypertensive subjects. METHODS: We measured 24-hour ambulatory
      BP (ABP) in 72 men (mean age 51 +/- 8 years), with OSA diagnosed on overnight
      sleep study. Measurements of BP were made at 15 min intervals for 24 h using
      either an Oxford Medilog ABP or Spacelabs 90207 recorder. All recordings were
      performed after > or = 3 week washout of anti-hypertensive drugs. The day-time
      monitoring period was defined as 07:00 hrs to 22:00 and night-time 22:00 to
      07:00. The ratio of night:day systolic and diastolic BP was calculated. RESULTS:
      The patients were obese (mean body mass index 33 +/- 5 kg/m2) with a central
      pattern of obesity (waist:hip ratio 0.99 +/- 0.14, normal < 0.94). The mean 24-h
      ABP (systolic/diastolic) was 138 +/- 18/88 +/- 12 mmHg. The mean daytime ABP was
      143 +/- 18/93 +/- 12 and night-time ABP 128 +/- 20/80 +/- 12 Hg. The night:day BP
      ratio was 0.90 +/- 0.07 (systolic) and 0.87 +/- 0.09 (diastolic) indicating that
      average BP was lower during the night. This pattern was similar in normotensive
      and hypertensive subjects. In contrast there was a significant relationship
      between increasing BMI and night:day blood pressure ratio (r = 0.56, p < 0.001)
      independent of the effects of OSA. CONCLUSION: In contrast to previous studies,
      men with OSA have a normal diurnal pattern of blood pressure levels. These
      findings suggest that any influence of OSA on BP is manifested throughout the 24
      h period.

PMID- 1345220
TI  - The Bergen Blood Pressure Study: definition of hypertensive and normotensive
      families based on 27 years' follow-up.
AB  - The familial aggregation of hypertension is well documented. However, many
      studies on the familial predisposition have suffered from insufficient knowledge
      of parental blood pressure (BP). In the present study, the family history is
      defined according to parental data from two BP surveys conducted almost 30 years
      apart. Data from a population screening in Bergen in 1963-64 were linked with
      information on marital status to define couples with or without a history of
      hypertension. Within the screened population a total of 344 married couples, 688
      individuals, matched defined age and BP criteria. Four hundred and thirty
      individuals, representing 270 of the 344 families initial included (79%),
      attended a follow-up examination in 1990. Six hundred and ninety-one offspring
      were registered. In all families represented at follow-up, parental BP data from
      the 1963-64 screening were available. In 160 families (noffspring = 393), both
      parents also attended the follow-up examination in 1990. In 23 families
      (noffspring = 54) both parents were hypertensive in 1963-64 as well as in 1990.
      In 22 families (noffspring = 55) both parents were normotensive at both
      examinations. Thus, a family data base which is assumed to be useful for studies
      on offspring with or without a family history of hypertension, has been
      established. The offspring studies include BP, 24-h ambulatory BP,
      electrocardiography, echocardiography, endocrine parameters, electrolytes and
      anthropometric variables.

PMID- 1345221
TI  - Blood pressure in middle-aged women: a comparison between office-, self-, and
      ambulatory recordings.
AB  - A blood pressure screening was carried out in women aged 40-64 years in a
      geographically defined area in southern Sweden; the attendance was 72%. Middle
      aged women classified as normotensives by standard criteria were found to differ
      from hypertensives also when blood pressure was recorded with non-invasive
      ambulatory technique; this was so when calculated for day, night, and 24 hours.
      The frequency of ambulatory blood pressure values > or = 140/90 mmHg was also
      significantly lower in normotensives than in hypertensives. The established way
      of diagnosing hypertension and normotension thus correlated well with the results
      of ambulatory monitoring in women. Furthermore, women had their highest blood
      pressure in the late afternoon and not in the mornings, as previously shown in
      men. This was so in all three groups of women (normotensives, borderline
      hypertensives, and hypertensives). This difference leaves room for speculation
      about different types of stress load during the day in men and women.

PMID- 1345224
TI  - Cholinergic system, heart rate, and blood pressure.

PMID- 1345225
TI  - Thoughts on the history of the dentistry in Scotland.

PMID- 1345223
TI  - Impaired vasodilator and chronotropic responses to 5-hydroxytryptamine in two
      models of hypertension-associated cardiac hypertrophy.
AB  - OBJECTIVE: In connection with hypertension, research concerning 5
      hydroxytryptamine (5-HT) receptors and subtypes in the cardiovascular system has
      so far been predominantly focused on various vascular tissues. In this study, the
      effects of 5-HT were investigated in isolated hearts with experimental cardiac
      hypertrophy. DESIGN AND METHODS: Cardiac hypertrophy was induced by stenosing the
      abdominal aorta (ASR) of 5-week-old Wistar rats. The functional response to
      serotonin was measured in unpaced, ASR hearts (18-20 weeks) and compared with
      those of "sham" operated SHR and WKY rats. RESULTS: The ASR, less hypertensive
      than SHR, showed more pronounced cardiac hypertrophy. The positive chronotropic
      and coronary vasodilator response to 5-HT was reduced in hypertrophied hearts
      from SHR and ASR when compared to "sham" operated and normotensive controls. The
      positive chronotropic effect of 5-HT could be antagonised with ketanserin,
      without affecting the coronary vasodilation. 5-HT did not induce any change in
      contractile force. CONCLUSIONS: Cardiac hypertrophy is associated with impaired
      coronary vasodilator and chronotropic responsiveness to serotonin. The
      chronotropic response to 5-HT is mediated by the 5-HT2-receptor subtype.

PMID- 1345222
TI  - The influence of chronic captopril treatment and its withdrawal on endothelium
      dependent relaxation.
AB  - The current experiments were designed to explore the relationship between the
      renin angiotensin system (RAS) and prostanoid formation in aortic ring
      preparations from spontaneously hypertensive rats (SHR). A further aim was to
      examine the mechanisms responsible for the reversal of the impaired acetylcholine
      (ACh) mediated relaxation induced by chronic administration of the angiotensin
      converting enzyme inhibitor captopril and the relationship of the ACh response to
      blood pressure. Rats were administered captopril (100 mg/kg/day) and their blood
      pressures monitored from 5 to 17 weeks of age. ACh-mediated relaxation was
      determined in aortic ring preparations from untreated and treated rats, and drug
      withdrawn rats. The influence of indomethacin, saralasin, SQ29548 and captopril
      on ACh-mediated responses was determined. It was found that chronic captopril
      treatment produced a marked suppression of the development of hypertension in the
      SHR. After the withdrawal of the drug the blood pressure remained significantly
      lower than in untreated animals for 4 weeks. ACh relaxation was impaired in SHR
      ring segments; this was reversed with captopril treatment and returned to the
      impaired state upon withdrawal of the drug. In vitro inhibition of the RAS did
      not significantly influence ACh relaxation. In contrast, impairment of the
      prostanoid system in vitro reversed the impaired relaxation. The results suggest
      that the influence of captopril on enhancing ACh relaxation in the SHR does not
      involve an acute interaction of local angiotensin II synthesis with prostanoid
      mechanisms. Importantly, the results highlight a dissociation between the
      impaired ACh relaxation and elevated blood pressure in the SHR.

PMID- 1345226
TI  - Two early eighteenth century dental advertisements from Norwich.

PMID- 1345227
TI  - History of dentistry in Japan and the Tokyo Dental College.

PMID- 1345228
TI  - [Echocardiographic evaluation of the size and systolic and diastolic function of
      heart muscle i patients with acromegaly].
AB  - In 20 patients with acromegaly, morphology of the heart and its systolic and
      diastolic function were studied by echocardiography, and growth hormone
      concentration was examined in the serum. Increased muscle mass of the left
      ventricle was found and that increase depended on disease duration and the growth
      hormone serum concentration. An increase was also shown of the left ventricular
      end-diastolic dimension, and the dimensions of left ventricle posterior wall and
      intraventricular septum, as well as an increase of end-systolic left ventricular
      dimension and of the size of the left atrium. Out of systolic function
      parameters, an increase was shown of stroke volume, cardiac output and cardiac
      index. In 40% of the studied patients an impairment was shown of left ventricular
      diastolic function but in a half of them no diseases other than acromegaly were
      found which could have been its cause.

PMID- 1345229
TI  - [Evaluation of the activity of angiotensin I converting enzyme (ACE) and of
      humoral immunity in patients with active pulmonary sarcoidosis].
AB  - In a group of 20 patients with active pulmonary sarcoidosis and in 20 healthy
      subjects, serum levels were determined of angiotensin I converting enzyme,
      immunoglobulins, and of the third and fourth complement components. An increased
      level of IgG and IgM was found in patients with sarcoidosis, as compared with the
      control group. High ACE levels were observed in the second and third phase of the
      disease. A tendency was also observed for simultaneous increase of IgG and ACE
      levels in patients with sarcoidosis.

PMID- 1345230
TI  - [Degree of ventilation disturbances in persons with occupational exposure to
      manganese].
AB  - In workers chronically exposed to manganese who showed spirometric abnormalities,
      an evaluation was done of the degree of ventilation disturbances in relation to
      age, duration of work, cigarette smoking, and the presence of chronic bronchitis.
      It was shown that of greatest influence on the loss of ventilation efficacy was
      cigarette smoking, and, in a lower degree, age. Chronic bronchitis however,
      caused no greater impairment of ventilation efficacy. Duration of work remained
      almost without influence on the degree of ventilation impairment.

PMID- 1345231
TI  - [Analysis of congenital malformations in newborns].
AB  - We analyzed data from 194 newborns with congenital malformations of central
      nervous, cardiovascular, gastro-intestinal, skeletal, genito-urinary systems and
      Down's syndrome. We detected that the highest frequency of congenital
      malformations occurred from may 1986 to december 1986. Congenital malformations
      were detected more frequently in female newborns and newborns delivered by
      multipara. The percentage of CNS malformations was constant but at the same time
      the number of other malformations were significantly changed. We made an attempt
      of statistical analysis of frequency and type of malformations taking into
      consideration possible influence of radiation during analyzed period.

PMID- 1345232
TI  - [The role of clinical examination in early diagnosis of testicular malignancies].
AB  - Sixty-seven patients were subjected to a retrospective analysis, who had been
      referred to the Department of Urology with suspected testicular malignancy. In
      every patient history was taken carefully with special attention paid to lacking
      testicular descensus in the past, testicular enlargement, pain, symptoms related
      to metastases, duration of symptoms until the beginning of appropriate treatment,
      the type of treatment, they had obtained before admission to the department. It
      was found that the most common symptom was painless testicular enlargement (82%
      of patients). However, there was a very long time between noting of the change by
      the patient and the beginning of appropriate treatment (on the average about 7.8
      months).

PMID- 1345233
TI  - [Treatment of chronic congestive heart failure using angiotensin converting
      enzyme inhibitors].

PMID- 1345234
TI  - [Crohn's disease with a severe course in a 12-year old girl].
AB  - A case is described of severe course of Crohn's disease in a 12-year-old girl.
      Discussing the period of three years of clinical observation, diagnostic and
      therapeutic difficulties are presented.

PMID- 1345235
TI  - [Cystic lymphangioma of the supraclavicular and right axillary fossae].
AB  - Five years ago, in a 34-year-old female patient a tumour developed in the right
      supraclavicular fossa which gradually increased in size. A few months ago she had
      noticed also a tumour in the axillary fossa on the same side. On physical
      examination, USG, and contrast X-ray it was found that it was a cyst of hour
      glass shape (narrowing of retro-clavicular). The cyst was removed totally.
      Histological examination: cystic lymphangioma (hygroma). The aetiology,
      diagnosis, and treatment of this type of tumours are discussed.

PMID- 1345236
TI  - [Usefulness of Dallop fascia prosthesis for the closure of recurrent inguinal
      hernia from intraperitoneal access].
AB  - Two patients are presented with recurrent inguinal hernias. In view of excessive
      tissue damage hernial sac adhesions and extensive scar, both hernias were closed
      from intraperitoneal access, suturing onto the borders of deep inguinal ring
      doubled leaflets of Dallop fascia. The authors consider this method of hernia
      closures as recommendable and safe.

PMID- 1345237
TI  - [Post-traumatic hepatic abscess in a 5-year old girl].
AB  - A case is presented of hepatic abscess probably of post-traumatic in a 5-year-old
      girl. The child was admitted to the hospital with high fever, decreased well
      being, abdominal pain, and vomiting. A preliminary diagnosis was made of
      septicaemia of unknown origin. During many days of observation the serous general
      condition with evidence of generalized infection persisted in spite of intensive
      antibiotic treatment. The correct diagnosis was made only after several USG
      examinations and completion of history data. A surgical operation with external
      drainage of the hepatic abscess resulted in complete cure.

PMID- 1345238
TI  - [Giant cystic kidney as the cause of mechanical ileus].
AB  - A rare case is presented of mechanical ileus caused by a giant cystic kidney.
      With absent symptoms from the urinary tract, the patient was operated on in
      emergency situation, and the diagnosis of polycystic renal degeneration in a 64
      year-old female patient was made during the operation. The fact is worth
      stressing of sure imposition in the X-ray image of the signs of ileus and of
      presence of fluid within numerous renal cysts, and in case of lacking other signs
      this may lead to diagnostic errors.

PMID- 1345239
TI  - [Rapid return of kidney function after treatment with plasmapheresis of active
      lupus glomerulopathy].

PMID- 1345240
TI  - [Crural amputation in the course of systemic lupus erythematosis].
AB  - A case is presented of a 22-year-old woman in whom, in the course of unrecognised
      systemic lupus erythematosus, spontaneous abortion, thrombosis of the femoral
      artery, and inflammatory changes of the crural vessels developed. The
      administered treatment with steroids failed to prevent crural amputation.

PMID- 1345241
TI  - [A case of Phalen-Dickson syndrome].
AB  - A case of dysplastic spondylolisthesis with a complete slipping of the L5
      vertebrae accompanied by neurological disorders and characteristic contracture of
      hamstrings (Tight Hamstrings Syndrome) has been described. This disease entity,
      described in literature, has a name of Phalen-Dickson Syndrome. Neurological
      disorders were caused by compression of radices at the level of the slipping.
      Surgical treatment were: laminectomy of the arcus of L5, decompression of the
      compressed radices with postero-lateral fusion of the L5-S1 segment without
      reduction of the slipping. The final, functional and radiological results were
      good.

PMID- 1345244
TI  - [Kidneys and arterial hypertension].

PMID- 1345243
TI  - [Treatment of hypercholesterolemia. II. Side effects of pharmacotherapy].

PMID- 1345242
TI  - [Treatment of hypercholesterolemia. I. Do side effects of exist when cholesterol
      levels are reduced?].

PMID- 1345246
TI  - Is the Centers for Disease Control's latest move a cop-out or political
      posturing?

PMID- 1345245
TI  - [Remarks on iodination of dietary salt in the province of Wroclaw].
AB  - A review is presented of KJ content in edible salt in the years 1975-1991. Salt
      samples were taken for study from shops and mass catering institutions in the
      Province of Wroclaw--a region of endemic struma. The content of KJ in salt was
      very low--on the average less than 10 mg/kg and very varied--from zero to over
      100 mg/kg.

PMID- 1345247
TI  - Physician bonding.

PMID- 1345248
TI  - Flash sterilization.

PMID- 1345249
TI  - Surgical masks.

PMID- 1345250
TI  - Upper extremity revascularization. Axillary-brachial bypass for temporal
      arteritis.
AB  - The perioperative nurse must understand the temporal arteritis disease process
      and surgical procedure so that he or she may function as an integral member of
      the surgical team. Preoperative, intraoperative, and postoperative nursing
      interventions are important and necessary to provide holistic patient care.

PMID- 1345251
TI  - Transanal endoscopic microsurgery. Minimal access rectal surgery.

PMID- 1345252
TI  - Returning to school for an advanced degree. A short-term investment with long
      term gains.

PMID- 1345253
TI  - Thought and talk. The intrapersonal component of human communication.
AB  - The intrapersonal component of human communication, self-talk, influences what we
      say and how we respond to another in interpersonal dialogues. A model of
      communication that incorporates the notion of self-talk, both that of the speaker
      and that of the listener, is useful in assisting nurses in making more realistic
      appraisals of communication interactions and addressing problems in communication
      failures.

PMID- 1345255
TI  - Position on HIV and nursing students defined.

PMID- 1345254
TI  - Latex allergy. A guideline for perioperative nurses.

PMID- 1345256
TI  - Vigilance, education are keys to overcoming laser safety complacency.

PMID- 1345257
TI  - Professional liability insurance coverage for perioperative nurses.

PMID- 1345258
TI  - Perioperative implications of tobacco use.

PMID- 1345259
TI  - Menopause and hyperlipidemia: pravastatin lowers lipid levels without decreasing
      endogenous estrogens.
AB  - In study 1, serum lipid and estrogen levels were determined in 30 women (aged 40
      to > 60 years). Total cholesterol (TC) levels increased significantly with age,
      but no significant association was found between TC levels and menopausal status.
      Hypercholesterolemia (TC > 220 mg/dl) was identified in 10 women and
      hypertriglyceridemia (> 150 mg/dl) in 5 women. Among women not receiving estrogen
      replacement therapy, a significant negative correlation was found between TC
      levels and estradiol-17 beta levels. In study 2, serum lipid and estrogen levels
      were determined in 74 women; 12 of the 74 were receiving conjugated estrogen for
      the treatment of the menopausal syndrome and 21 hyperlipidemic women were
      receiving pravastatin (2.5 to 30 mg daily). Among postmenopausal women, high
      density lipoprotein cholesterol levels were significantly higher and low-density
      lipoprotein (LDL) cholesterol levels significantly lower in the estrogen-treated
      than untreated women. Serum TC and LDL cholesterol levels were significantly
      reduced during pravastatin treatment. Levels of endogenous estrogens (estradiol
      17 beta, estrone, and estrone sulfate) were not significantly affected by
      pravastatin treatment. The results indicate that pravastatin can be used to
      reduce hyperlipidemia in menopausal women without affecting endogenous estrogen
      levels.

PMID- 1345260
TI  - Ambulatory blood pressure monitoring. A tool for more comprehensive assessment.
AB  - AIMS: To investigate the usefulness of more comprehensive blood pressure
      measurements, made during daily life, in the diagnosis and treatment of
      hypertension. METHODS: A blood pressure screening was carried out in middle-aged
      men and women in Kavlinge, a municipality in southern Sweden. Subjects were
      classified according to Swedish standard criteria. Ambulatory blood pressure (amb
      BP) was recorded in a random sample of normotensives and borderline hypertensives
      as well as in all the untreated hypertensives identified at screening and willing
      to participate. A subgroup of borderline hypertensives also carried out self
      measurements of blood pressure (self-BP) both at work and at home. The blood
      pressure lowering efficacy of atenolol 50 mg o.d. and enalapril 20 mg o.d. was
      compared in hypertensives at rest, during 24 hours, and during dynamic and
      isometric exercise. The efficacy of enalapril and lisinopril (two ACE inhibitors
      with different durations of action) were also compared, with special focus on the
      early morning hours. RESULTS: Men and women classified as normotensives clearly
      differed from those with hypertension, also when blood pressure was recorded with
      ambulatory technique. The number of correctly classified subjects did not differ
      between self-BP and office-BP; combining the two added little. Atenolol reduced
      blood pressure better during dynamic exercise than did enalapril, while there was
      no significant difference in effect between enalapril and lisinopril, not even 18
      24 hours post-dose. CONCLUSION: More comprehensive blood pressure measurements
      should be considered in the evaluation of hypertension treatment. Office BP,
      however, seems a reasonably good tool for diagnosing hypertension.

PMID- 1345263
TI  - [Respiratory infections].

PMID- 1345261
TI  - Structural cardiovascular changes in essential hypertension. Studies on the
      effect of antihypertensive therapy.
AB  - These studies were undertaken to evaluate different manifestations of structural
      cardiovascular changes and the effects of antihypertensive therapy in essential
      hypertension. A meta-analysis of 109 studies that had examined the effect of
      different pharmacological blood pressure lowering regimens on left ventricular
      structure, examined by echocardiography, was undertaken to increase the
      statistical power, to resolve uncertainty and to improve the accuracy of
      estimation of the magnitude of effect. Strict preset criteria were applied. The
      effect of different drugs in monotherapy and in particular first line
      antihypertensive therapies were compared, using an analysis of covariance
      (ANCOVA). ACE-inhibitors, beta-blockers and calcium antagonists all reduced left
      ventricular mass (LVM) through a reduction in wall hypertrophy, the effect being
      most pronounced with ACE-inhibitors. Conversely, diuretics reduced LVM mainly
      through a reduction of left ventricular volume. Previously untreated males (n =
      28, 86 kg, 46 years, 27 kg/m2) with non-malignant essential hypertension (supine
      diastolic blood pressure (DBP) > 95 mmHg 3-4 times (in triplicate) on placebo)
      were randomized to long-term double-blind treatment with enalapril (E) or
      hydrochlorothiazide (H). There were no significant differences between the groups
      at baseline. Vascular alterations in the retina (eyeground photo, refined
      grading), cardiac morphology (M-mode echocardiography, ASE), structural vascular
      changes of the hand (plethysmography, minimal resistance (Rmin)), total
      peripheral resistance ((TPR), calculated from dye-dilution) and blood pressure
      (intraarterial) were significantly interrelated at baseline except LVM and Rmin.
      After 6 months of therapy, E reduced the signs of vascular changes in the retina
      as well as Rmin in the hand circulation, while H did not change or increased
      these structural vascular changes. The blood pressure lowering effect of E
      (mainly through lowering of TPR) tended to be more pronounced, measured both
      intraarterially and indirectly, than that seen with H (mainly through lowering of
      cardiac output), however, there were no significant differences. LVM decreased
      progressively with E while the effect of H was non-significant. E reduced wall
      thickness but not left ventricular diameter and also improved left ventricular
      distensibility significantly. The effect on cardiac morphology was significantly
      different between therapies when taking change in blood pressure into account.
      After the longest follow-up on monotherapy (18 months) E had reduced LVM by 2.7
      g/mmHg and H (14 months) by 1.3 g/mmHg (significant for E only). In univariate
      analysis the changes in cardiovascular structure were significantly related to
      the changes in the Renin-Angiotensin-Aldosterone System (RAAS).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1345262
TI  - [Respiratory infections--still an essential problem in health care].

PMID- 1345264
TI  - [Return of pertussis].

PMID- 1345265
TI  - [Infections and asthma].

PMID- 1345266
TI  - [Microbiological diagnosis of respiratory infections].

PMID- 1345267
TI  - [Acute respiratory tract infection].

PMID- 1345268
TI  - [Sinusitis as a diagnostic problem].

PMID- 1345269
TI  - [Diagnosis of otitis media in children].

PMID- 1345270
TI  - [Problems related to the treatment of otitis media].

PMID- 1345271
TI  - [Pharyngitis].

PMID- 1345273
TI  - [Bronchitis].

PMID- 1345272
TI  - [Obstructive respiratory infections in children].

PMID- 1345274
TI  - [What does the radiograph tell about respiratory infections?].

PMID- 1345275
TI  - [Pneumonia in adults].

PMID- 1345276
TI  - [Pneumonia in children].

PMID- 1345277
TI  - [Is pneumonia immunization necessary in the elderly?].

PMID- 1345279
TI  - [Endocrinological effects of cytokines].

PMID- 1345278
TI  - [Lactobacillus in the treatment of gastrointestinal diseases].

PMID- 1345281
TI  - [New prognosticators in urinary bladder carcinoma].

PMID- 1345280
TI  - [Garlic--a spice or a medicine?].

PMID- 1345282
TI  - [The role of helper t-cell subsets in infectious diseases and allergy].

PMID- 1345283
TI  - [Clinical diagnosis of breast cancer].

PMID- 1345284
TI  - [Reliability of brachial-ankle pressure gradient in the diagnosis of vascular
      diseases].

PMID- 1345285
TI  - [Separation of symphysis pubis and sacroiliac joint during labor].

PMID- 1345286
TI  - [Thrombotic thrombocytopenic purpura].

PMID- 1345287
TI  - [Treatment of acute pancreatitis].

PMID- 1345288
TI  - [Chronic back pain--new information about the mechanism of back pain].

PMID- 1345290
TI  - [Mucosa--the first specific immune defense system in the body].

PMID- 1345289
TI  - [Health benefits of contraception].

PMID- 1345291
TI  - [Regulation of melanoma growth].

PMID- 1345292
TI  - [Liver transplants in Finland: the first 100 patients].

PMID- 1345293
TI  - [Allergy to coined money].

PMID- 1345294
TI  - [Transient blindness--a rare symptom in severe cases of pre-eclampsia].

PMID- 1345295
TI  - [Tubulo-interstitial nephritis and uveitis in a 13-year old boy].

PMID- 1345296
TI  - [The adverse effects of contact lenses].

PMID- 1345297
TI  - [Minimal inhibitory and bactericidal concentrations of some antiseptics and
      disinfectants against strains of hospital origin].
AB  - The MIC in solid media and the B.M.C. by the dilution-neutralization test using
      sterile water, was determined using 10 antiseptics and disinfectants with 70
      strains of 10 species of Gram negative bacteria more frequently causing
      nosocomial infections in Ciudad Sanitaria Reina Sofia, Cordoba, in Spain.
      Relationship between the two tests was searched with no positive results. The
      more effective antiseptics were silver nitrate and chlorhexidine, the less active
      was phenol. Activity of some antiseptics was similar at 30 or 60 minutes of
      contact with the microorganisms.

PMID- 1345298
TI  - Neonatal septicaemia due to K. pneumoniae. Septicaemia due to Klebsiella
      pneumoniae in newborn infants. Nosocomial outbreak in an intensive care unit.
AB  - The authors report a nosocomial infection outbreak by Klebsiella pneumoniae,
      observed in neonates at a gyneco-obstetrical hospital from Mexico City. Forty six
      newborns presented one or more infections due to K. pneumoniae during their stay
      in neonatal care units, between October 3 and November 12, 1988. Sepsis was
      documented in 41 cases by clinical picture and routine laboratory exams,
      including one positive, blood culture at least. The most frequent invasive
      procedures practiced in these patients were catheterization and ventilatory
      support. K. pneumoniae was isolated as well from several environmental sources
      that could have led to infection of patients. Treatment of cases was initiated
      with ampicillin-amikacin, however, therapeutic failure with a lethality rate of
      50% (14/28) and results of antimicrobial susceptibility conducted to treatment
      with cefotaxime. Fifteen out of 19 patients receiving the cephalosporin survived.
      To prevent outbreaks like the one presented here, we concluded that appropriate
      measures dealing with hygiene and education of personnel plus monitoring of
      bacterial susceptibility to antimicrobials, should prove successful in our
      environment.

PMID- 1345299
TI  - [Preparation and use of fish fillet infusion as a basic medium for culturing
      bacteria].
AB  - The authors present the first results on the utilization of fish infusion (IFP)
      as a basic medium for the cultivation of bacteria. The infusion was obtained from
      a common marine fish, corvina (Micropogonias furnieri) according to the technique
      used in the preparation of beef infusion broth. Streptococcus pyogenes, S.
      pneumoniae, Neisseria meningitidis, Campylobacter jejuni, Escherichia coli,
      Klebsiella pneumoniae, Serratia marcescens, Pseudomonas aeruginosa,
      Staphylococcus aureus and Bacillus subtilis were cultured in liquid and solid
      media prepared with IFP as well as in recommended standard media. Solid media
      used for cultivation of S. pyogenes, S. pneumoniae, N. meningitidis and C. jejuni
      were supplemented with 5% of defibrinated sheep blood and for the latter,
      substances recommended to increase aerotolerance were included in solid and
      liquid media. All of these strains grew on the media prepared with IFP except S.
      pneumoniae when cultured in IFP diluted 1:2 with a sodium chloride solution. Only
      S. pyogenes produced colonies smaller than those of the standard medium. No more
      differences were detect in the observation of colony morphology. The growth of E.
      coli, K. pneumoniae, S. marcescens, P. aeruginosa, S. aureus and B. subtilis was
      measured in liquid media after 8 hours. In solid media, the growth index was
      expressed by dividing the number of colonies produced in IFP-agar and Nutriente
      Agar by the number of colonies on Trypticase soy agar plates. Some differences
      were observed in colonial size and morphology when compared with those generated
      in standard media. The average value obtained from the analyses of total proteins
      by biuret reaction in twelve batches of IFP was 5.03 mg/ml. The experiments
      showed that culture media prepared with IFP supported the growth of bacterial
      strains used in this work. It suggests that fish infusion has promising
      conditions of being an alternative substrate for cultural purposes.

PMID- 1345300
TI  - [Envelope and membrane glycoproteins of Herpes simplex virus].
AB  - A bibliographic update on the herpes simplex virus (HSV) envelope is made with
      special emphasis on the membrane glycoproteins and their role in adsorption,
      spreading and escape of the immune response. The HSV has at least seven
      glycoproteins on its envelope; three out of them are essential for in vitro
      replication, they are designated as gB, gD and gH; four are dispensable: gC, gE,
      gI and gG. Their main functions are: gC, gB and gD attach the virion to the cell
      surface, binding to molecules of heparan sulfate on the plasma membrane. Later,
      the three essential glycoproteins induce fusion of the viral envelope with the
      plasma membrane, through the gD receptor. To evade the immune response, the HSV
      has two major mechanisms: gE and gI are Fc receptors of immunoglobulin G; while
      gC acts as a receptor for the C3b fragment of the third component of complement.
      Finally, gG and gC have epitopes responsible for the antigenic differences
      between HSV type 1 and HSV-2. These glycoproteins have several possible
      applications for the development of a synthetic vaccine, and for treatment of
      herpetic recurrent disease.

PMID- 1345302
TI  - [The oral route: an access port for Trypanosoma cruzi].
AB  - Rats and mice were inoculated by oral route with T. cruzi from: 1. Infected mice
      blood, 2. Experimentally infected triatomines feces, 3. Experimentally infected
      alive triatomines, and 4. Free cell cultures. Mice showed to be more susceptible
      to the infection than rats. Mice exhibited to be infected: 30% with blood forms,
      85% with triatomines feces, 75% with alive triatomines and 35% with culture
      forms. Rats exhibited to be infected: 10%, with blood forms, 45% with triatomines
      feces, 60% with alive triatomines and 25% with culture forms. In both species we
      observed that metacyclic trypomastigotes originated higher infection percentage
      than blood and culture forms. With these results we confirm that oral route is a
      probable way of transmission of T. cruzi and under standardized conditions, it
      represents a better experimental inoculation route than intraperitoneal route.

PMID- 1345301
TI  - [Recognition by immunoelectroblotting of antigens from Taenia solium and its
      larva].
AB  - Golden hamster (Mesocricetus auratus) were infected with cysticerci of Taenia
      solium. Groups of three were bled and killed weekly up to 15 weeks recording the
      number of implanted adults in the small intestine. A longitudinal study on the
      antibody response against adult and larvae Ags was carried out, as well as
      against Ags of H. nana. By ELISA, antibodies against larvae and adult Ags of T.
      solium were detected since the first week, showing a peak at 3 and 5 weeks
      respectively. At 14 weeks antibodies levels were very low, which is the time when
      the parasite is eliminated. The response against Ags of H. nana was very low and
      disappeared at 4 weeks. By western blot we found that the infected hamsters can
      distinguish specific stage Ags both in the adult and larvae of T. solium. After
      12 weeks only the adult was recognized, the Ags of H. nana were recognize in
      western blot only during the first week.

PMID- 1345303
TI  - [Interaction of a mixture of epimastigotes and tripomastigotes from a culture of
      a Mexican isolate of Trypanosoma cruzi with mouse macrophages].
AB  - Chagas disease, a cause of important morbo-lethality in Latinamerica, is produced
      by a protozoan which has a circulating and tissular phase the Trypanosoma cruzi.
      Adhesion between T. cruzi and phagocytes is the first step in cellular
      parasitism, which has a central role in pathogenesis. Although there are studies
      on parasite phagocyte interaction with some strains of T. cruzi, and it is known
      that biological variation does exist. We now report the first studies with a
      mexican isolate using a mix of different phases of T. cruzi obtained from
      acellular culture resembling the natural conditions. Murine macrophages adheres
      to epimastigotes, transitional trypomastigotes and metacyclic trypomastigotes
      since the first minutes of observation, progression on cell-cell interaction was
      demonstrated, there were no differences among parasite faces however, in some
      cases there was a failed adhesion, this suggest a possible parasite evasion
      mechanism. These studies limited only to morphologic aspects the adhesion
      phenomena, should be pursued.

PMID- 1345304
TI  - [Presence of antibodies against Toxoplasma gondii in adolescents from the African
      continent].
AB  - It was determined the presence of antibodies anti-T. gondii in young, 13-16 year
      old, belonging to Republic Arab Saharaui; Popular Republic of Angola; Ethiopia
      and Republic of Ghana. From a total of 707 sera analyzed, the 71.43% of them
      showed the presence of specific antibodies. The prevalence of antibodies did not
      differ significantly (P > 0.05) between males and females in Angola and Republic
      Arab Saharaui. It was found a significant difference (P < 0.0001) among
      countries.

PMID- 1345305
TI  - Genetic characterization of the mechanism by which certain strains of Escherichia
      coli survive in high kanamycin concentrations.
AB  - By genetic studies, it was tried to find the mechanism by which a bacterial
      fraction from different isolated clinical cultures resistant to 25 micrograms/ml
      of kanamycin can grow in media containing 500 micrograms/ml of kanamycin (at a
      frequency of about 10(-5)). This study was done in six clinical isolates of
      Escherichia coli resistant to more than three antibiotics. The results from the
      bacterial fraction (subpopulation) resistant to high concentrations of kanamycin
      in the level of resistance to aminoglycoside and non-aminoglycoside antibiotics,
      in the conjugation experiments, and in the percentage of resistant bacteria to
      500 micrograms/ml of kanamycin when the subpopulations were subsequently
      cultivated in the absence of antibiotics suggest that genetic amplification
      occurred when one of the strains was growing in the presence of 500 micrograms/ml
      of kanamycin. Moreover, this strain increased its frequency of survival in high
      kanamycin concentrations when it was transduced by bacteriophage P1, propagated
      in cultures resistant to 500 micrograms/ml of kanamycin.

PMID- 1345306
TI  - [Decrease of spontaneous mutations in Haemophilus influenzae caused by
      transformation with its own DNA irradiated with near-ultraviolet light].
AB  - Transforming DNA containing the streptomycin resistance marker, was irradiated
      for 8 h with broad near ultraviolet light (325-400 nm) at pH 4.8, and the
      inactivation kinetics determined. After selection of streptomycin resistant
      transformants, they were grown until a turbidity of 150-200 Klett units. In these
      cultures we looked for new markers coming from the irradiated transforming DNA.
      We looked and found the novobiocin resistance marker and one that conveys to
      protoporphyrin IX utilization, measured as an increase in the mutation frequency
      of these markers in the streptomycin resistant population. In other experiments,
      we found a decline in spontaneous mutation frequency for the same markers in the
      cells transformed with irradiated DNA. This last finding rises the possibility of
      alterations on the mutator genes as a result of near ultraviolet irradiation.

PMID- 1345307
TI  - Partial characterization of a novel chemotactic factor produced by macrophages.
AB  - The production of substances by lymphocytes or macrophages under activation
      involved in regulating immune responses, has led us to study a new macrophage
      factor with chemotactic activity for lymphocytes. This factor is produced early
      in the immune response activation (6 hours, in vitro) by peritoneal exudate
      adherent cells under stimulation with sheep red blood cells (SRBC) and it induces
      lymphocyte chemotaxis. We have confirmed this factor is a polypeptide susceptible
      to proteolytic digestion. Besides, its receptor on T cells requires the presence
      of glycosylated sites, specially sialic acid. It was determined that such a
      chemotactic factor was not interleukin-1, a well-characterized mitogenic and
      chemotactic substance for T lymphocytes.

PMID- 1345308
TI  - [Sensitivity and specificity of mouse peritoneal macrophages in the diagnosis of
      Chlamydia trachomatis infections].
AB  - We analyzed the sensitivity and specificity of mouse peritoneal macrophages (MPM)
      for the diagnosis of infection by Chlamydia trachomatis. Fifty seven samples were
      studied, 25 of them were from cervix and 32 were from bronchial aspiration,
      resulting 29 positive by immunofluorescence in McCoy cells and only 16 in MPM.
      The sensitivity and specificity for MPM were 55% and 96% respectively. We
      concluded that McCoy cells are the election cells for the diagnosis of Chlamydia
      infection. However, the MPM can be useful in the recuperation of this
      microorganism, if no other method is available.

PMID- 1345309
TI  - Humoral response to blastospores and mycelium in mice injected with different
      doses of Candida albicans.
AB  - An indirect immunofluorescence assay was carry out to determine the IgM and IgG
      antibody responses to yeast and mycelial forms of Candida albicans in mice
      injected with a 5 x 5(5) and 5 x 10(7) live cells suspensions. Prior adsorption
      of the serum samples with heat-killed blastospores enabled us to follow the
      specific antimycelial response which were detected considerably later than
      expected. Slow level of antibodies were obtained within an infection of 5 x 10(5)
      cell for both antibody classes and for yeast and mycelial forms. When a 5 x 10(7)
      cell dose was used for inoculation, maximum titers of antibodies to blastospores
      and mycelium in non-adsorbed sera appeared almost simultaneously (days 15 and 13,
      respectively). When serum samples from mice infected with the same dose were
      previously adsorbed with blastospores, the antimycelium antibodies for both types
      of Igs, were detected delayed during the infection course. In this case the
      higher titer for IgG appeared on day 33 and on day 23 for IgM. We suggest that
      the high titer obtained with the blastospore forms for the 5 x 10(7) cell dose
      may be due to a major immunogenicity of this forms, for to induce an immune
      response in the host, or that the delay in the antimycelium antibodies detection
      could be due to that a blastospore form is the predominant in the infection early
      stages. Implications of this fact for pathogenesis are discussed.

PMID- 1345310
TI  - Phagocytic activity of circulating polymorphonuclear leukocytes from patients
      with carcinoma of the uterine cervix.
AB  - Peripheral blood leukocytes and the sera from 10 healthy women and 12 patients
      with invasive carcinoma of the cervix (stages I to IV), showed no differences in
      their capacity to inhibit the replication of an invasive strain of Escherichia
      coli. The serum from only one patient was unable to arrest the bacterial growth.
      The quantitation of myeloperoxidase in the polymorphonuclear leukocytes from 21
      patients (stages I to III) and 11 healthy women showed, however, a lower activity
      in the group of patients (P = 0.001). Most patients also showed lymphocytopenia,
      neutrophilia, and eosinophilia but normal counts of total leukocytes.

PMID- 1345311
TI  - [Bacteriologic profile of the Andalien estuary (Chile). Count, biomass, and
      productivity].
AB  - Bacterial population, biomass and productivity from the Andalien estuary
      (Concepcion, Chile) were investigated by measuring the viable counts and the
      total cell population by epifluorescence. There were differences in the viable
      counts obtained during fall and spring, but not in total counts. The bacterial
      productivity in the estuary and the nearest sea was increased during the spring,
      probably due to a larger proportion of metabolic active cells. The results also
      suggest an increased bacterial activity in the estuary and the nearest sea for
      the spring time.

PMID- 1345312
TI  - [Preparation and evaluation of coagglutination reagents for the identification of
      Vibrio cholerae 01. Its trial during a cholera outbreak in Minatitlan, Veracruz].
AB  - This study was realized in Minatitlan, Veracruz during a cholera outbreak. 169
      rectal swabs were taken from hilles and their contacts. They were transfer
      alkaline peptone water for enrichment to V. cholerae and incubated for 8 hrs to
      37 degrees C, 70 were positive for V. cholerae in both techniques. The
      coagglutination was done with a reagent prepared at the Instituto de Diagnostico
      y Referencia Epidemiologicos of Mexico and the culture were also performed in the
      same Institute. We obtained 100% of sensitivity and specificity of co
      agglutination in relation with culture. This results gave the possibility to use
      this kind or reagents for a rapid presumptive diagnosis of cholera.

PMID- 1345313
TI  - Identification of enteropathogens in infantile diarrhea in a study performed in
      the city of Posadas, Misiones, Republica Argentina.
AB  - The following work informs of the results of isolation, frequency and
      distribution of enteropathogens in children under five years old, without
      previous antibiotic treatment, less than seven days with diarrhoea, ambulatory or
      in Hospital "Dr. Ramon Madariaga" de Posadas, Misiones, Republica Argentina, from
      June 1986 to May 1989. From a total of 972 children with diarrhoea, 78% required
      to be hospitalized. The greatest number of cases were found during spring and
      summer in children from 1 to 11 months of age. Distribution of the main
      enteropathogens was: enteropathogenic Escherichia coli (EPEC) (29.4%), parasites
      (22%), Shigella (16.3%), enterotoxigenic Escherichia coli (ETEC) (14%) and
      rotavirus (12.9%). Highest incidence of rotavirus was registered in the coldest
      months and Shigella, ETEC, Salmonella and parasites in the warm months. The group
      of most affected children were from 1 to 11 months of age, with higher incidence
      of EPEC, Salmonella and rotavirus, and parasites were found in older children.
      ETEC and Shigella had no relationship with the age of children. The most frequent
      association was EPEC with rotavirus. This is the first finding of Salmonella
      zaiman in humans and of Salmonella hadar in Argentina. Cryptosporidium,
      etiological agent of serious diarrhoea in the immunocompetent, was isolated in
      3.9% of our cases.

PMID- 1345314
TI  - [Characterization of a substance which protects Klebsiella pneumoniae from the
      bactericidal effect of normal human serum].
AB  - Chemical composition of a substance produced by Klebsiella pneumoniae which is
      accumulated in chemically defined medium was determined. This substance (the
      protective factor) protects the bacterium from being killed by normal human
      serum. Protective factor was treated with DNase, lysozyme and an alkaline
      protease. The two former enzymes did not affect the protective factor. On the
      other hand, when alkaline protease was used, the protective activity was totally
      lost. Results showed that the protective factor is a protein.

PMID- 1345315
TI  - [Diagnosis from urine culture in 4 hours using the DIRAMIC-03 system].
AB  - The results obtained with DIRAMIC-03 System for its application of detection of
      urinary infection by utilization of simulated samples and real samples from
      hospital service, are shown. It was possible to establish a methodology based on
      conductimetry which perform a diagnostic in four hours with a global effectivity
      of 86% in relation with the traditional methods.

PMID- 1345317
TI  - [Presence of neuraminidase in Rhodnius prolixus infected with Trypanosoma
      rangeli].
AB  - Using three different methods, the activity of neuraminidase was studied in the
      promesenteron, postmesenteron, rectal ampulla, haemolymph and salivary glands in
      600 Rhodnius prolixus experimentally infected with Trypanosoma rangeli stock San
      Agustin. The haemagglutination method with peanut lectin, and the fluorescence
      test with peanut lectin conjugated with fluorescein isothiocyanate, and the
      fluorescence emitted by 4-methylumbelliferone showed in all cases the presence of
      neuraminidase in the supernatant culture of T. rangeli in Tobie's medium between
      8 to 15 days growth. None of the three methods was able to detect the presence of
      neuraminidase in R. prolixus infected with T. Rangeli, thus suggesting that this
      enzyme is not produced in vivo, and consecutively is not implicated in the
      pathogenicity that this trypanosome has to its vector.

PMID- 1345318
TI  - Recognition of Trichinella spiralis muscle larvae antigens by sera from human
      infected with this parasite and its potential use in diagnosis.
AB  - Human antibody response to total soluble extract of Trichinella spiralis muscle
      larvae (TSE) was analyzed by Western blot. The most frequently recognized
      antigens had molecular weights of 96, 67, 63, 60, 55 and 47 kDa. An antigenic
      fraction containing two peptides with M.W. of 43, 47 kDa from the parasite (p43,
      47 Ts L1) was isolated by elution from polyacrylamide gel slabs. It was used as
      antigen in an ELISA test and compared to that of TSE. Serum samples from 51
      symptomatic trichinellosis patients--43 with high antibody levels to TSE, 5 of
      them with positive biopsy and 8 with low levels of these antibodies--as well as
      38 from asymptomatic individuals from the area where the trichinellosis outbreaks
      had occurred and 43 from apparently healthy individuals from a non-endemic area,
      37 from patients with intestinal parasitic infections caused by helminth and
      protozoan parasites--11 from recurrent and 26 from non-recurrent disease--were
      analyzed by ELISA using both antigens. The ELISA using p43, 47 Ts L1 detected all
      trichinellosis patients with high antibody levels as well as 6 out of 8 of those
      with low antibody levels. All control groups were negative. Therefore, this
      purified fraction allowed the ELISA to be more specific and sensitive for human
      trichinellosis diagnosis.

PMID- 1345316
TI  - [Diagnosis of blackleg by direct immunofluorescence in bovine bone marrow].
AB  - On smears of marrow-bone death bovines, presumptively diagnostic of black-leg, we
      have carried out the direct immunofluorescence test (IF). We used two labelled
      immunosera with fluorescein isothiocyanate. The immunosera wer prepared with the
      reference strain 5078 of Clostridium chauvoei as following: a) a cellular extract
      obtained with veronal buffer 0.045 M pH = 8.6, and b) a flagellar suspension
      obtained by agitation with glass beads, centrifuged at 3,500 x g, and centrifuged
      again at 16,000 x g during 20 min at 4 degrees C. Both antigenic preparations
      were injected into rabbits, five doses (0.2, 0.4, 0.8, 1.6 and 3.2 ml) each by
      i.v. route. Control positive strain of C. chauvoei were used, and control
      negative strains of C. septicum and C. perfringens were used too. Of all 56
      examined samples, 26 (47.5%) gave positive IF test. These results had a 100% of
      correlation by culture and biochemical identification.

PMID- 1345319
TI  - Tropical oils: nutritional and scientific issues.
AB  - Individually and in combination with other oils, the tropical oils impart into
      manufactured foods functional properties that appeal to consumers. The use of
      and/or labeling in the ingredient lists give the impression that these oils are
      used extensively in commercially processed foods. The estimated daily intake of
      tropical oils by adult males is slightly more than one fourth of a tablespoon
      (3.8 g), 75% of which consists of saturated fatty acids. Dietary fats containing
      saturated fatty acids at the beta-position tend to raise plasma total and LDL
      cholesterol, which, of course, contribute to atherosclerosis and coronary heart
      disease. Health professionals express concern that consumers who choose foods
      containing tropical oils unknowingly increase their intake of saturated fatty
      acids. The saturated fatty acid-rich tropical oils, coconut oil, hydrogenated
      coconut oil, and palm kernel oil, raise cholesterol levels; studies demonstrating
      this effect are often confounded by a developing essential fatty acid deficiency.
      Palm oil, an essential fatty acid-sufficient tropical oil, raises plasma
      cholesterol only when an excess of cholesterol is presented in the diet. The
      failure of palm oil to elevate blood cholesterol as predicted by the regression
      equations developed by Keys et al. and Hegsted et al. might be due to the
      dominant alpha-position location of its constituent saturated fatty acids. If so,
      the substitution of interesterified artificial fats for palm oil in food
      formulations, a recommendation of some health professionals, has the potential of
      raising cholesterol levels. A second rationale addresses prospective roles minor
      constituents of palm oil might play in health maintenance. This rationale is
      founded on the following observations. Dietary palm oil does not raise plasma
      cholesterol. Single fat studies suggests that oils richer in polyunsaturated
      fatty acid content tend to decrease thrombus formation. Anomalously, palm oil
      differs from other of the more saturated fats in tending to decrease thrombus
      formation. Finally, in studies comparing palm oil with other fats and oils,
      experimental carcinogenesis is enhanced both by vegetable oils richer in linoleic
      acid content and by more highly saturated animal fats. The carotenoid
      constituents of red palm oil are potent dietary anticarcinogens. A second group
      of antioxidants, the tocotrienols, are present in both palm olein and red palm
      oil. These vitamin E-active constituents are potent suppressors of cholesterol
      biosynthesis; emerging data point to their anticarcinogenic and antithrombotic
      activities. This review does not support claims that foods containing palm oil
      have no place in a prudent diet.

PMID- 1345320
TI  - Clinical impact of introducing thrombolytic and aspirin therapy into the
      management policy of a coronary care unit.
AB  - PURPOSE: To evaluate the impact of introducing thrombolytic and aspirin therapy
      into the management policy of a coronary care unit, with particular reference to
      its effects on the hospital course of nonselected patients with acute myocardial
      infarction. End points chosen were the utilization of thrombolytic and aspirin
      therapy, hospital mortality, discharge diuretic requirements, and the incidence
      of ventricular fibrillation and cardiogenic shock. PATIENTS AND METHODS: A total
      of 336 patients with acute myocardial infarction were studied, comprising
      consecutive admissions to the coronary care unit over two separate 12-month
      periods: January to December 1986 (n = 158) and September 1989 to August 1990 (n
      = 178), before and after thrombolytic and aspirin therapy had been introduced
      into the management policy of the unit. RESULTS: Thrombolytic and aspirin therapy
      was given to 87% and 93%, respectively, of all patients in the 1989/1990 cohort.
      This high treatment rate led to substantial improvements in morbidity and
      mortality. Thus, comparison of the 1986 and 1989/1990 cohorts showed reductions
      in hospital mortality (24% to 11%, p less than 0.005), ventricular fibrillation
      (22% to 13%, p = 0.05), and cardiogenic shock (20% to 6%, p less than 0.001),
      particularly in patients aged over 60. Reductions in the incidence of lesser
      degrees of heart failure are reflected in the proportions of patients discharged
      with diuretic requirements, which declined from 43% in 1986 to 22% in 1989/1990
      (p less than 0.001). The duration of hospital stay for patients who survived
      showed no change between 1986 and 1989/1990, but time spent in the coronary care
      unit decreased from 3.1 +/- 1.8 to 2.1 +/- 1.4 days (p less than 0.001).
      CONCLUSION: The great majority of nonselected patients with acute myocardial
      infarction are candidates for thrombolytic and aspirin therapy, which can be
      given safely, leading to profound reductions in mortality and the incidence of
      major complications, particularly in the older age group.

PMID- 1345321
TI  - Antibacterial activity of some triclosan-containing toothpastes and their
      ingredients.
AB  - The antibacterial activity of 4 triclosan-containing toothpastes was compared to
      a conventional fluoride dentifrice and triclosan and sodium lauryl sulphate
      (SLS), both singly and in combination. A panel of 17 bacteria was tested by an
      agar dilution method. At concentrations typical of those found in toothpastes,
      triclosan and SLS displayed approximately equal antibacterial activity. A paste
      containing triclosan and zinc citrate appeared more active than the other
      triclosan pastes which, in general, showed marginal superiority over the
      conventional paste. SLS, although included in dentifrice formulations for its
      detergent properties, may significantly contribute to the antibacterial profile
      of a product. The need for appropriate controls when evaluating experimental
      toothpastes is emphasized.

PMID- 1345322
TI  - Symptomatic lower urinary tract infection induced by cooling of the feet. A
      controlled experimental trial.
AB  - We conducted an open, non-randomized experimental study as a first step to find
      out whether cooling of the feet may cause symptomatic lower urinary tract
      infection (UTI) in cystitis-prone women. Twenty-nine healthy women, aged 19-68
      (mean 42.5) years, who had had three or more symptomatic episodes of UTI during
      the previous 12 months were included. They registered symptoms and carried out a
      strip urinalysis at each urination during a control period of 72 hours. Their
      lower legs and feet were then immersed in increasingly cold water for 30 minutes.
      Another 72-hour period of registration followed. Six subjects developed acute
      distal urinary symptoms at a mean of 55 (95% confidence interval 50 to 61) hours
      after the cooling, compared with none in the control period. Five of the six had
      bacteriologically verified lower UTI (P = 0.03 v. the control period). Cooling of
      the feet seems to provoke symptomatic lower UTI in cystitis-prone women.

PMID- 1345323
TI  - [Cerebral hemorrhage as the presenting form of Sneddon syndrome].

PMID- 1345324
TI  - Canine distemper virus transcripts sequenced from pagetic bone.
AB  - Paget's disease is a chronic disease of the skeleton which is believed to be
      caused by a persistent virus of the paramyxovirus family. There is still conflict
      as to the precise identity of the virus(es) involved in causing this disease. Our
      previous results using in situ hybridisation have implicated distemper as a
      possible cause of this disease. In order to confirm these results, we have
      reverse transcribed RNA from pagetic bone and have specifically amplified for
      distemper and measles sequences using the polymerase chain reaction (PCR)
      technique. We have found that 8/13 of the patients examined had distemper and
      1/10 cases had measles nucleic acids sequestered within their bone cells. One
      individual was found to have both viruses sequestered in his bone cells. Dideoxy
      sequencing of the distemper virus PCR products revealed 2% base pair changes in
      the nucleic acid sequences relative to the Onderstpoort strain of canine
      distemper. We can conclude that in Paget's disease, canine distemper and possible
      other paramyxoviruses reside in bone cells and that the persistent nature of the
      virus may be due to mutations in the viral genome.

PMID- 1345326
TI  - P450IA2 and omeprazole.

PMID- 1345327
TI  - Preventive cardiology. The experts's views. Gothenburg, June 5, 1992.
      Proceedings.

PMID- 1345325
TI  - Vegetable oil fortified feeds in the nutrition of very low birthweight babies.
AB  - Two kinds of oils (i) Polyunsaturated fatty acids (PUFA) rich Safflower oil, and
      (ii) Medium chain triglyceride (MCT) rich Coconut oil were added to the feeds of
      46 very low birthweight (VLBW) babies to see if such a supplementation is capable
      of enhancing their weight gain. Twenty two well matched babies who received no
      fortification served as controls. The oil fortification raised the energy density
      of the feeds from approximately 67 kcal/dl to 79 kcal/dl. Feed volumes were
      restricted to a maximum of 200 ml/kg/day. The mean weight gain was highest and
      significantly higher than the controls in the Coconut oil group (19.47 +/- 8.67
      g/day or 13.91 g/day). Increase in the triceps skinfold thickness and serum
      triglycerides were also correspondingly higher in this group. The lead in the
      weight gain in this group continued in the follow up period (corrected age 3
      months). As against this, higher weight gain in Safflower oil group (13.26 +/-
      6.58 g/day) as compared to the controls (11.59 +/- 5.33 g/day), failed to reach
      statistically significant proportions, probably because of increased
      statistically significant proportions, probably because of increased steatorrhea
      (stool fat 4+ in 50% of the samples tested). The differences in the two oil
      groups are presumably because of better absorption of MCT rich coconut oil.
      However, individual variations in weight gain amongst the babies were wide so
      that some control babies had higher growth rates than oil fortified ones. The
      technique of oil fortification is fraught with dangers of intolerance,
      contamination and aspiration. Long term effects of such supplementation are
      largely unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345328
TI  - The Quinapril Ischemic Event Trial (QUIET).

PMID- 1345329
TI  - Syndrome X.

PMID- 1345330
TI  - Male fat distribution and cardiovascular risk.

PMID- 1345331
TI  - Hemodynamics of the male fat distribution pattern.
AB  - A male fat distribution pattern with abdominal obesity increases the risk for
      hypertension and cardiovascular disease, and is closely linked to a number of
      metabolic aberrations including insulin resistance. Recent observations suggest
      that changes in the peripheral vasculature may be of pathophysiological
      importance for the development of hypertension and its associated metabolic
      disturbances. We therefore investigated the hemodynamic correlates of abdominal
      obesity. A central fat distribution was found to be associated with a specific
      hemodynamic profile, characterized by elevated total peripheral resistance and
      lower cardiac output. In response to sympathoadrenal activation during mental
      stress, the normal cardiac output-dependent pressor response was reversed into a
      systemic vasoconstrictor response. There was a direct relationship between degree
      of abdominal obesity (expressed as waist-hip ratio) and fasting serum insulin.
      Furthermore, the stress-induced increase in total peripheral resistance
      correlated positively with fasting serum insulin concentration, whereas there was
      an inverse relation between serum insulin and cardiac output and heart rate. In a
      second study, the circulatory responses to stress during physiological
      hyperinsulinemia were investigated. During hyperglycemic hyperinsulinemia the
      central hemodynamic response to stress was changed into a systemic
      vasoconstrictor response. In the forearm the physiological vasodilation during
      stress was markedly attenuated, suggesting that insulin may have peripheral
      vascular effects. In conclusion, central obesity is associated with a specific
      hemodynamic pattern characterized by higher total peripheral resistance and lower
      cardiac output, and a vasoconstrictor response to psychosocial stress. This
      hemodynamic response pattern may be related to insulin metabolism.

PMID- 1345332
TI  - Cholesterol reduction in single and multifactor randomized trials: relationship
      to CHD incidence and total mortality as found by meta analysis of twenty-two
      trials.
AB  - This paper reports on a meta analysis in twenty-two randomized both single and
      multifactor trials regarding the effect of designed cholesterol reduction on
      total mortality and CHD incidence. Per cent reduction in CHD incidence was 2.5
      for every per cent associated net reduction in total cholesterol, but was only
      0.74% for total mortality. Since total net reduction in cholesterol was about 5%
      in all trials combined, the number of participants was far too small to
      demonstrate a significant expected reduction of 4% in total mortality. However,
      the 4% reduction lies just outside the observed 95% confidence limits of the
      overall estimate of effect on total mortality (OR = 1.02; CL 0.97, 1.07). It is
      concluded that cholesterol reduction must be much larger than 5% to be able to
      reduce the relative risk of CHD substantially and total mortality moderately.

PMID- 1345333
TI  - High cholesterol and triglyceride values in Swedish males and females: increased
      risk of fatal myocardial infarction. First report from the AMORIS (Apolipoprotein
      related MOrtality RISk) study.
AB  - In over 300,000 Swedish males and females aged 20 to 79 years total cholesterol
      and triglycerides were measured consecutively between 1985 and 1989. In a
      subsample of about 35,000 individuals apolipoprotein (apo) B (indicating
      atherogenic) and apo A-I (anti-atherogenic) were also measured. In the age group
      40-49 years, 24% of the males and 12% of the females had hypercholesterolemia (>
      or = 6.5 mmol/L) and 14% and 3%, respectively had hypertriglyceridemia (> or =
      2.3 mmol/L). Combined hyperlipidemia occurred in this age group in 7% of the
      males and in 1% of the females and was more common in males. In the same age
      group, 21% of the males and 8% of the females had high atherogenic apo B values
      (> 1.5 g/L). Low apo A-I was found in the whole population (20-79 years) in 13%
      of the males and in 10% of the females and varied only little with age. In the
      AMORIS (Apolipoprotein related MOrtality RISk) study these individuals are
      followed prospectively. The relations between lipids and apo B and apo A-I levels
      and risk for fatal acute myocardial infarction (AMI) are analyzed to investigate
      which of these lipids/apolipoproteins best predict AMI either as single
      determinants or in combination. After a mean observation time of about 22 months
      there is a 3-6-fold increase in AMI in relation to increasing cholesterol levels
      in males of 40-59 years. The largest increase was seen in the 40-49-year age
      group. A similar relationship was also found for triglycerides and AMI.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1345335
TI  - Hypertension, hyperlipidemia, insulin resistance and obesity: parts of a
      metabolic syndrome.

PMID- 1345336
TI  - The key issues in preventive cardiology.
AB  - A number of risk factors/indicators for cardiovascular disease, mainly stroke and
      coronary artery disease, have been established. Most powerful among the
      traditional risk factors are hypertension, cigarette smoking and elevated serum
      cholesterol. All three can successfully be modified by therapeutic intervention,
      which in turn will result in reduced risks. In recent years several novel risk
      indicators have been identified. The most powerful of these appears to be
      increased left ventricular mass, particularly when diagnosed with
      echocardiographic technique. Again, it is possible to reduce this risk factor,
      for instance by antihypertensive therapy, but the independent risk reduction
      attributable to this manoeuvre remains to be determined. Other novel risk
      indicators are male type adipose distribution, reduced insulin sensitivity and a
      number of newly detected lipoprotein fractions. At present little is known about
      the value of intervention against these factors in terms of risk reduction. It
      can be concluded that a structured concerted effort at reducing established risk
      factors such as arterial hypertension, elevated serum cholesterol and cigarette
      smoking is desirable for forming the basis of preventive strategies in
      cardiology. As regards some of the novel risk indicators, some of which appear
      more powerful than the old established ones, further research is needed before a
      clear opinion can be formulated regarding the value of intervention.

PMID- 1345334
TI  - Treatment of hypertension.

PMID- 1345337
TI  - Ca(2+)-induced persistent protein kinase C activation in rat hippocampal
      homogenates.
AB  - Protein kinase C (PKC) is thought to play an important role in neuronal function
      by mediating changes in synaptic strength. Specifically, it has been argued that
      persistent PKC activation underlies the maintenance of long-term potentiation
      (LTP) of synaptic transmission in the hippocampus, a model widely used to study
      mammalian learning and memory. Because the induction of LTP is known to be
      dependent upon Ca2+ influx into the postsynaptic neuron, we investigated Ca(2+)
      dependent mechanisms that operate to elicit persistent PKC activation in the
      hippocampus. Hippocampal homogenates were incubated with Ca2+ for a brief period
      and subsequently assayed for persistent changes in basal (Ca(2+)-independent) PKC
      activity, using the selective PKC substrate neurogranin(28-43) (NG(28-43)). After
      Ca2+ incubation, basal PKC phosphorylation of NG(28-43) was increased and
      expression of the increased activity could be inhibited by PKC(19-36), a
      selective peptide inhibitor of PKC. These data indicate the presence of a
      persistently activated form of PKC in Ca(2+)-pretreated hippocampal homogenates.
      The persistently activated PKC was localized to the soluble fraction of
      homogenates. Generation of the soluble, persistently activated form of PKC was
      blocked by the calpain inhibitor, leupeptin, suggesting a proteolytic activation
      of PKC. Column chromatography and Western blots indicated the presence of PKM, a
      proteolytic fragment of PKC that is active in the absence of calcium,
      diacylglycerols, or phospholipid cofactors. Thus, Ca2+ induces proteolytic
      activation of PKC in hippocampal homogenates. This suggests that proteolytic
      activation is a plausible candidate as a mechanism underlying the persistent
      activation of PKC associated with LTP.

PMID- 1345338
TI  - Selection of cDNAs for phosphodiesterases that hydrolyze guanosine 3';5'
      monophosphate in Escherichia coli.
AB  - A genetic selection procedure has been developed which makes the growth of E.
      coli dependent on expression of a cGMP phosphodiesterase cDNA. E. coli does not
      contain a cGMP phosphodiesterase, and guanine auxotrophs cannot extract the
      guanine from cGMP. If a functional cGMP phosphodiesterase is introduced, then
      guaA auxotrophs will grow on cGMP as a guanine source. The method also selects
      GMP synthetase cDNAs, which complement the guanine auxotrophy directly.
      Expression of a Dictyostelium discoideum or human heart cyclic nucleotide
      phosphodiesterase cDNA permits growth of the E. coli guaA auxotroph in the
      presence of cGMP. Several commercial cDNA libraries were corrupt and contained
      phosphodiesterase and/or GMP synthetase sequences that were from a contaminating
      DNA source.

PMID- 1345339
TI  - Effect of parathyroid hormone on rat renal calcium/calmodulin-dependent protein
      kinase II.
AB  - Rat parathyroid hormone (PTH) stimulates cAMP-dependent protein kinase and
      protein kinase C activity in the kidney. However, PTH increases intracellular
      Calcium in primary cultures of proximal tubular cells. We have investigated the
      possibility that PTH also stimulates Calcium/calmodulin-dependent protein kinase
      II (CaM kinase II). We have employed the tandem chromatographic column method,
      using synthetic peptide as a substrate, to measure the renal CaM kinase II
      activity. PTH (250 nM) stimulated CaM kinase II activity by about 50% after 15
      sec., and activity returned to baseline by 2 min. Calmodulin antagonists
      significantly impaired the stimulatory action of PTH whereas basal levels of CaM
      kinase II activity were relatively unaffected. This study demonstrates that PTH
      does activate CaM kinase II in renal tissue, and suggests another pathway for the
      actions of PTH in the kidney.

PMID- 1345340
TI  - Phospholamban-modulated Ca2+ transport in cardiac and slow twitch skeletal muscle
      sarcoplasmic reticulum.
AB  - The correlation between phospholamban and sarcoplasmic reticulum Ca(2+)
      transporting ATPase levels and the magnitude of phospholamban-mediated
      stimulation of sarcoplasmic reticulum Ca2+ transport was examined in microsomes
      prepared from rabbit and canine cardiac, slow twitch and fast twitch skeletal
      muscle. Phospholamban was absent from microsomes prepared from fast twitch
      skeletal muscle but present at comparable levels in microsomes prepared from
      cardiac and slow twitch skeletal muscle. Levels of Ca(2+)-transporting ATPase
      were higher in microsomes prepared from slow twitch skeletal muscle than in
      microsomes prepared from cardiac muscle, however, and ratios of phospholamban to
      Ca(2+)-transporting ATPase were several fold greater in microsomes prepared from
      cardiac muscle than in microsomes prepared from slow twitch skeletal muscle.
      Stimulation of ATP-dependent Ca2+ transport following phosphorylation of
      phospholamban by cAMP-dependent protein kinase or incubation with anti
      phospholamban monoclonal antibody was observed only in cardiac muscle microsomes.
      These observations indicate that phospholamban, while present in both cardiac and
      slow twitch skeletal muscle, may be involved in the hormonal regulation of
      sarcoplasmic reticulum Ca2+ transport only in the former, and that the lack of
      phospholamban-mediated stimulation of Ca2+ transport in slow twitch skeletal
      muscle sarcoplasmic reticulum may result from the lower ratio of phospholamban to
      Ca(2+)-transporting ATPase in this tissue.

PMID- 1345341
TI  - Lipopolysaccharide stimulates phosphorylation of eukaryotic initiation factor-4F
      in macrophages and tumor necrosis factor participates in this event.
AB  - Bacterial lipopolysaccharide (LPS) produces rapid changes in macrophage protein
      synthesis and function. Phosphorylation of the 25 kDa mRNA cap-binding protein
      (eIF-4E) in model systems regulates the efficiency of protein synthesis. We
      report that both LPS and tumor necrosis factor-alpha (TNF-alpha) stimulate
      phosphorylation of eIF-4E and the p220 component of eIF-4F in bone marrow-derived
      macrophages. Moreover, anti-TNF-alpha antibodies inhibit LPS-stimulated
      phosphorylation of eIF-4E and p220 by 43% (+/- 6%) and 50% (+/- 5%),
      respectively. Our results indicate that LPS stimulates eIF-4F phosphorylation by
      a TNF-alpha-dependent mechanism, and suggest that phosphorylation of eIF-4F might
      play a role in the post-transcriptional regulation of gene expression in
      macrophages exposed to LPS.

PMID- 1345342
TI  - Activation of G-proteins induces Ca2+ oscillations with hyperpolarizing K+
      currents in pancreatic beta-cells.
AB  - Activation of G-proteins by internal perfusion with GTP-gamma-S or external
      application of carbachol resulted in oscillations of cytoplasmic Ca2+ in isolated
      mouse pancreatic beta-cells. The Ca2+ transients were associated with the
      generation of K+ currents sufficiently pronounced to induce marked pulses of
      hyperpolarization. The oscillatory G-protein response remained largely unaffected
      when altering the membrane potential. The oscillations became less frequent in
      the presence of 1 mM neomycin and disappeared when the cells were internally
      perfused with 100 micrograms/ml heparin. The frequency of the oscillations was
      positively correlated with the basal level of cytoplasmic Ca2+. Addition of Ca2+
      to the internal perfusion medium increased the oscillatory rate and buffering of
      the ion with Indo-1 or EGTA had the opposite effect. It is concluded that G
      protein activation results in cyclic mobilisation of intracellular calcium
      mediated by inositol-1,4,5-triphosphate and that the basal concentration of
      cytoplasmic Ca2+ is an important determinant for the frequency of the
      oscillations.

PMID- 1345343
TI  - Heterogeneity of hepatic protein tyrosine phosphatases.
AB  - We have identified multiple members of the protein tyrosine phosphatase family in
      three subcellular compartments from rat liver; membrane, cytoskeleton and
      cytosol. Characterization based on substrate specificity, size, and reactivity
      with an anti-peptide antiserum against human placental PTP1B indicate the
      presence of at least three PTPases in Triton X-100 extracts of particulate
      membranes. Of these, one of 600 kDa possesses characteristics of a transmembrane,
      receptor-like enzyme. A fourth particulate PTPase (70 kDa) represents a distinct
      cytoskeletal PTPase. Cytosol contains one main PTPase species which was detected
      as a 41 kDa protein in Western immunoblots. These data indicate the existence of
      multiple hepatic PTPases whose differences in structure and subcellular
      localization may reflect functional heterogeneity.

PMID- 1345344
TI  - Pronounced differences between native Chinese and Swedish populations in the
      polymorphic hydroxylations of debrisoquin and S-mephenytoin.
AB  - The frequency of poor metabolizers of debrisoquin was low and similar in four
      different native Chinese nationalities. In a total sample of 695 Chinese
      subjects, only seven (1.01%) had a urinary ratio between debrisoquin and 4
      hydroxydebrisoquin greater than 12.6, which is the antimode between poor
      metabolizers and extensive metabolizers in white populations. This is
      significantly lower than the 6.82% found in 1011 white Swedish healthy subjects
      (p less than 0.0001). Admixture analysis indicated the occurrence of two
      distributions within extensive metabolizers among both Chinese and white
      subjects. The mean of the distribution of metabolic ratios among Chinese
      extensive metabolizers was shifted toward higher values compared with Swedish
      extensive metabolizers (p less than 0.01). The frequency of poor metabolizers of
      S-mephenytoin was higher in 137 Chinese (14.6%) than in 488 Swedish (3.3%)
      subjects (p less than 0.0001). Our findings imply that drugs metabolized by these
      two polymorphic hydroxylases should be prescribed in different dosages to Chinese
      and white subjects.

PMID- 1345345
TI  - [Early diagnosis in rheumatoid polyarthritis].

PMID- 1345346
TI  - [Nonsteroidal anti-inflammatory agents of the group of oxicam derivatives].

PMID- 1345347
TI  - [Cyclophosphamide--an effective immunomodulator in treating inflammatory
      rheumatism and severe collagenoses].
AB  - After 30 years since the synthesis of cyclophosphamide and 25 years since its
      first clinical utilization (V.Ciobanu), authors offer an actualized review of the
      data of pharmacokinetics, pharmacodynamics, pathopharmacology and clinical
      therapeutics, which make of cyclophosphamide an efficacious, manageable and safe
      drug in the treatment of the aggressive forms of collagenoses or inflammatory
      rheumatism. The criteria of therapeutic indication and clinical surveillance are
      mentioned.

PMID- 1345348
TI  - [Common osteoporosis: the anatomicoclinical and therapeutic aspects].

PMID- 1345349
TI  - [The rheumatological manifestations of infection with the human immunodeficiency
      virus (HIV)].

PMID- 1345350
TI  - [The immunobiological aspects of patients with systemic lupus erythematosus and
      their blood relatives].

PMID- 1345351
TI  - [Nosological and diagnostic problems in spondyloarthropathies].

PMID- 1345352
TI  - [Peptic hemorrhagic gastroduodenitis].

PMID- 1345353
TI  - [Acute erosive gastritis and Helicobacter pylori infection].

PMID- 1345355
TI  - [Congestive-hemorrhagic gastropathy in liver cirrhosis. The endoscopic aspects].

PMID- 1345354
TI  - [The diversity of upper digestive hemorrhage in cirrhotic patients].

PMID- 1345357
TI  - [Endemic goiter in northeastern regions of Poland].

PMID- 1345356
TI  - [Immediate hemostasis, hemorrhagic recurrences and early mortality following
      sclerotherapy compared with conventional therapy in active variceal hemorrhages
      in cirrhotic patients].

PMID- 1345358
TI  - [Epidemiologic examinations of goiter in the population of the Sejny community].
AB  - The study was aimed at the evaluation of incidence of goiter in the population of
      the community of Sejny. The survey comprising 1520 subjects revealed the presence
      of thyroid enlargement in 31.8% of the subjects studied, indicating the
      occurrence of a mild endemy. The facts speaking for this type of endemy are:
      predominance of cases with goiter of OB or I degree (83%), higher incidence of
      goiter in women than in men (3.3 times), occurrence of nodular goiter in 12% of
      cases with goiter, and sporadic appearance of hypothyroidism. Goiter endemy in
      the population of this area can be attributed to such goitrogenic factors as low
      level of iodine and high content of calcium in the water, tobacco smoking, and a
      habit of drinking tap water.

PMID- 1345359
TI  - [Epidemiology of thyroid diseases in the population of the Sejny community after
      the atomic catastrophe in Chernobyl].
AB  - The survey carried out in 1990 covering the population of Sejny community,
      sponsored by the Ministry of Health and Welfare, program MZXVII, demonstrated the
      occurrence of goiter in 33.6% of studied persons. Such an incidence can rightly
      be recognized as an endemy. Predominance of cases with small or moderate
      enlargement of the thyroid (OB and I), low percentage of nodules (18%), and 2.8
      times more frequent occurrence of goiter in women allows o characterize the
      endemy as mild. The percentage of goiter in this population does not differ from
      that found in this area before the Chernobyl disaster. However a small increase
      in the incidence of thyroid enlargement in a group of boys of age between 17 and
      19 years, and an increase in percentage of nodular goiter in whole population was
      noted. The questionnaire studies confirmed in addition a high effectiveness of
      mass iodine prophylaxis introduced after the atomic disaster, especially in the
      population of developmental age. However, because of the latency period
      concerning the possible effects, the results obtained will be verified in the
      course of long-term prospective studies.

PMID- 1345360
TI  - [Relationship between thyroid size and urinary concentration of iodine in the
      population of Bialystok].
AB  - The survey carried out in May 1991 in the city of Bialystok comprised 308
      children of age between 8 and 14 years and 116 young adults. In each of the
      studied subjects the size of the thyroid was measured by ultrasonography and
      iodine concentration determined in a randomly voided sample of urine. Body weight
      and height of the subjects have also been measured. In about 50% of the subjects
      studied (58.4% of children, 38.5% of men and 58.4% of women) the presence of
      goiter accompanied by a low urinary iodine concentration (median--2.0
      micrograms/ml) was found. A significant negative correlation between the thyroid
      size and urinary iodine concentration, and lack of relation between the former
      and TSH concentration, have been found. No relation was observed between the
      presence of goiter and the inadequate physical development in the children
      studied. Insignificantly elevated TSH levels without accompanying clinical
      symptoms of hypothyreosis were observed in 8.7% of children, 3.8% of women and
      5.1% of men studied. Higher prevalence of goiter found as compared to the results
      previously obtained in the same area can be related on the one to the use of more
      precise methods and on the other to real worsening of the situation due to
      discontinuation of obligatory iodine prophylaxis in the country more than 10
      years ago.

PMID- 1345361
TI  - [Behavior of thyroid autoantibodies in persons inhabiting an endemic goiter
      area].
AB  - The study was aimed at investigating the occurrence of thyroid autoantibodies
      (ATMA and TGA) in persons inhabiting the area of goiter endemy of mild degree.
      The survey comprised 1508 persons of age ranging from 3 to 68 years. The subjects
      studied have been divided into the groups taking into account age, sex, degree of
      thyroid enlargement (according to WHO, 1974), and the characteristics of the
      goiter. The occurrence of ATMA or TGA antibodies was demonstrated in 17% of the
      subjects. An increase in the incidence and titer of thyroid autoantibodies with
      age was observed. The occurrence of thyroid autoantibodies was observed more
      frequently in the subjects with parenchymatous goiter. No correlation was found
      between the incidence of the antibodies and goiter size. Thyroid autoantibodies
      have also been found in 10% of subjects without goiter. The results obtained do
      not indicate convincingly the role of the thyroid autoantibodies in the
      pathogenesis of endemic goiter.

PMID- 1345362
TI  - [Ultrasonographic pattern and levels of thyrotropin and antithyroid antibodies in
      patients with recurrent neutral goiter after subtotal thyroidectomy].
AB  - The study comprised 65 women (mean age 43 years) with the recurrent goiter after
      subtotal strumectomy. All patients were subjected to ultrasonographic examination
      using a sonograph Sonoline LM (Siemens) with 7.5 MHz head. The study was aimed
      at: 1) assessment of etiology of goiter recurrence, 2) assessment of changes in
      the thyroid parenchyma, 3) detection of the occurrence of heterogeneous
      structures, such as nodules, cysts and calcifications. It was found that goiter
      recurrence appeared mainly in the patients subjected to surgery because of
      neutral nodular goiter. The observed changes in the thyroid stump, such as
      heterogeneous structure of parenchyma, generalized cyst-like spaces and nodular
      structures mainly of mixed type or of solid, normo-echogenic or hyper-echogenic
      type, were associated with high levels of THS and the presence of antithyroid
      antibodies in blood serum. In patients with evidently high TSH levels and
      positive with respect to occurrence of antithyroid antibodies, the nodular
      structures were more numerous and of larger size. In can be concluded that
      ultrasonography provides a valuable noninvasive tool for the evaluation of
      morphological structure of the recurrent goiter.

PMID- 1345363
TI  - [Comparative analysis of fine needle aspiration biopsy results performed in the
      laboratory of thyroid diseases, University School of Medicine in Lodz in 1985-91
      with results of postoperative histopathologic examinations].
AB  - From 1985 to 1991 there were 5889 fine-needle aspiration biopsies of thyroid
      performed in our laboratory. 703 cytological diagnoses based on biopsy specimens
      taken from 679 patients, were compared with the results of postoperative
      histopathological examinations. There were 14% non-diagnostic biopsies. The
      statistical analysis was performed considering difficulties in differentiation
      between follicular adenomas and follicular carcinomas. Difficulties in evaluation
      of biopsies of cystic lesions were also considered. The results of cytological
      and histopathological examinations were agreeing with one another in 88% cases.
      In regard to diagnosis of malignant neoplasms, the sensitivity of the cytological
      investigation was equal to 63% and the specificity equaled to 90%. While
      considering detection of papillary carcinomas, the sensitivity was equal to 67%.
      Our results are in a compliance with the view, that the fine-needle aspiration
      biopsy is a useful method in a preoperative diagnosis of thyroid lesions.

PMID- 1345364
TI  - [Role of chemotherapy in the treatment of anaplastic thyroid cancer --personal
      observations].
AB  - Results of chemotherapy applied in 23 patients with anaplastic thyroid cancer are
      presented. Chemotherapy combined with local treatment is a suggested therapy for
      treatment the locally advanced anaplastic thyroid cancer.

PMID- 1345365
TI  - [Monitoring of treatment for hypothyroidism with L-thyroxine].
AB  - The study was aimed at the evaluation of treatment of hypothyroidism with L
      thyroxine administration monitored by the determination of T3 and T4
      concentrations. The investigations were carried out in a group of 57 patients
      with hypothyroidism including 37 patients with autoimmune etiology of
      hypothyroidism, 12 patients after strumectomy and 8 patients after treatment with
      131J. The administration of L-thyroxine at a dose of 2 micrograms/kg/day
      effectively eradicated all symptoms of the disease and led to the normalization
      of blood serum T3 and T4 values in the majority of patients with autoimmune
      hypothyroidism. So the majority of women required the daily dose of L-thyroxine
      of 100-150 micrograms, and the majority of men 125-175 micrograms. Lower dosage
      of L-thyroxine (50-100 micrograms daily) was required to attain euthyroid state
      in some patients with postoperative or postradiation hypothyroidism. Monitoring
      of the therapy by the determination of blood serum T3 and T4 concentrations
      greatly facilitated the proper choice of the therapeutic dose of L-thyroxine as
      the return of the thyroid hormone concentrations to normal usually brought about
      the complete remission of symptoms of the disease. The exception from this rule
      was only in the case of patients with arterial hypertension and coronary disease
      in whom, because of the side-effects, lower dosage of L-thyroxine (usually 50
      micrograms daily) must have been applied to attain the optimal improvement. The
      treatment with L-thyroxine caused much less side-effects as compared to the
      therapy using the dessicated thyroid preparations (Thyroideum).

PMID- 1345366
TI  - [Method for detection of antitubulin antibodies. Results of assays in autoimmune
      thyroid diseases].
AB  - A cytoskeletal protein--tubulin was isolated from the cerebral tissue by the
      sequential microtubule polymerization and depolymerization technique described by
      Schelansky. The purity of the isolated protein was verified by SDS polyacrylamide
      gel electrophoresis. The binding reaction with monoclonal antibodies against
      various cytoskeletal proteins confirmed the presence of pure tubulin. The
      isolated tubulin was used as reactant in a solid phase radioimmunoassay for the
      detection of antitubulin antibodies in tubulin-coated plastic tubes. Antitubulin
      antibody assays were performed in 20 cases of hypothyroidism and 56 cases of
      Graves' disease. In 70 percent of cases of hypothyroidism and 50 percent of cases
      of Graves' disease the levels of antitubulin autoantibodies were elevated. The
      highest titres of antibodies had some patients with Graves' disease. The
      antitubulin autoantibodies were of the IgM class.

PMID- 1345367
TI  - [Evaluation of a method for determining ACTH concentration in samples of serum
      obtained by catheterization of inferior petrosal sinuses in diagnosis of
      Cushing's disease].
AB  - A method consisting in the catheterization of lower petrosal sinuses aimed at
      obtaining blood samples for the determination of ACTH concentration has been
      applied in diagnostically difficult cases of Cushing's disease. The appearance of
      ACTH concentration gradient between the blood originating from the immediate
      vicinity of pituitary and the peripheral venous blood confirmed the hypophyseal
      etiology of hypercortisolemia. The gradient of ACTH concentration between the two
      petrosal sinuses made possible the localization of a microadenoma in the anterior
      lobe of pituitary. The diagnostic conclusions obtained by the above method have
      been confirmed during the surgery.

PMID- 1345368
TI  - Stimulation of rat pituitary tumoral cell proliferation in vitro by tetra- and
      pentagastrin.
AB  - The effects of the active gastrin fragments, penta- and tetragastrin on the
      incorporation of tritiated thymidine into the rat pituitary tumoral cells were
      investigated in vitro. The significant stimulation of 3H-thymidine incorporation
      was observed as an effect of the investigated substances. The putative role of
      gastrin as an autocrine growth factor active in pituitary tumorigenesis was
      discussed.

PMID- 1345369
TI  - Premature menarche--a legend or a defined clinical syndrome.
AB  - The properness of diagnosing the premature menarche as isolated clinical syndrome
      is often questioned. A long-term observation od 2 girls with premature menarche
      has been described. A discussion is presented about the role of imbalance within
      the hypothalamus-pituitary-gonads axis and the role of disturbances in peripheral
      responsiveness to sex hormones in the patho-mechanism of premature menarche.

PMID- 1345370
TI  - [Luteinizing hormone receptors in human chorionic gonadotropin--structure and
      properties].

PMID- 1345371
TI  - Occupational exposures to mists and vapours from strong inorganic acids and other
      industrial chemicals. Working Group views and expert opinions, Lyon, 15-22
      October 1991.

PMID- 1345373
TI  - Hydrochloric acid.

PMID- 1345372
TI  - Sulfur dioxide and some sulfites, bisulfites and metabisulfites.

PMID- 1345374
TI  - Diethyl sulfate.

PMID- 1345375
TI  - Diisopropyl sulfate.

PMID- 1345376
TI  - 1,3-Butadiene.

PMID- 1345377
TI  - Occupational exposures to mists and vapours from sulfuric acid and other strong
      inorganic acids.

PMID- 1345378
TI  - Malignant tumours after renal transplantation.
AB  - The incidence of malignant tumours in 570 patients with kidney transplants was
      examined. It was found to be 20-30 times higher than in the average (normal)
      population. In accordance with the literature, mainly skin cancers were observed,
      but at variance with these data, the number of lymphoreticular malignancies was
      small. On the basis of their study, the authors emphasize the oncogenetic effect
      of immunosuppression. By comparing the conventional (AZA+PRED) and Cyclosporine
      (CYA+PRED) treatments, they point out that this risk should be taken into
      consideration even in Cyclosporine therapy which has otherwise a much more
      favourable effect.

PMID- 1345379
TI  - The technique of obtaining pancreatic segments in dogs: surgical-anatomical
      aspects.
AB  - The technique of obtaining pancreatic segments was studied in 60 mongrel dogs by
      removing the right pancreatic lobe. At the same time comparative surgical
      anatomical examinations were performed for the detection of the vascular
      variations of the right pancreatic segment. In 83% of the cases the arterious and
      venous systems were suitable for gaining grafts (Types I-II). In 12% the segment
      was suitable for grafting only if the venous network had an optimal course (Type
      III), while in 5% the segment was unsuitable because it did not have a suturable
      arterial stump (Type IV).

PMID- 1345380
TI  - Laparoscopic appendectomy.
AB  - This study contains a brief review of the changes in the technique of
      laparoscopic appendectomy. The authors' experiences with the methods they applied
      are reported. The authors emphasize on the benefits of laparoscopic appendectomy
      as opposed to traditional appendectomy, and advocate its wide-range application.

PMID- 1345381
TI  - Follow-up examinations of laparoscopic cholecystectomies.
AB  - The postoperative complaints of patients having been subjected to laparoscopic
      cholecystectomy have been studied. Residual gallstones involving clinical
      symptoms have not been observed. Right subcostal pain, meteorism, and nausea due
      to faulty diet showed a slight difference in favour of the laparoscopic method
      when compared to traditional surgery. The laparoscopic method was qualified as
      excellent by over 95 per cent of the patients.

PMID- 1345382
TI  - Esophageal carcinoma study in 83 cases.
AB  - The surgical procedures for carcinoma of oesophagus with and without thoracotomy
      are compared. Since March 1987: 65 patients who were resectable (78.4%) underwent
      surgical procedures during a 40 months period. The ratio of male to female was 3
      to 2, mostly seen in 6th decade (45%) of life. Tumor site: 6% upper 1/3, 46%
      middle and 48% lower third. The surgical resection procedures were: 53.8% McKeown
      and Akiyama et al. 33.9% transhiatal (Orringer) the rest Ivor-Lewis and
      endoesophageal pullthrough E.E.P.T. /24, 25/. No mortality occurred during
      operations, but fistula was seen in 20% of cases and the most frequent morbidity
      was pulmonary complications, which was seen 3 times more in procedures including
      thoracotomy. Increasing the mortality rate also comparing to just one death
      (4.6%) in transhiatal method. In 24-62 months follow-up period including 3/4 of
      the cases, the survival was 33.3% for transhiatal Esophagectomy = THE and 34.4%
      for other procedures (Transthoracic esophagectomy = TTE).

PMID- 1345383
TI  - Influence of bile on the severity of acute experimental pancreatitis induced by
      closed duodenal loop in rat.
AB  - The study was performed to assess the ethiological role of bile in acute
      pancreatitis provoked by closed duodenal loop in rat. In group I a closed
      duodenal loop was created by method of Nevalainen. A similar operation was
      performed in group II, but the common pancreatico-biliary duct was ligated just
      under the liver. In the control group (group C) only the mobilization of duodenum
      was performed. After 24 hours the mortality rate was 20% in group I, but 0% in
      group II and C. The amount of ascitic fluid showed significant elevation in group
      I versus II and group C, and in group II as compared to group C, too. The serum
      amylase was significantly higher in group I than group II and group C, and in
      group II was also higher as compared to group C. Serum total protein differed
      significantly between all groups, while albumin and total calcium were
      significantly lower in group I than group II, but group II was only slightly
      reduced versus group C. Histology showed no differences between groups I and II,
      but both differed significantly from group C. In conclusion bile seems to be an
      aggressive factor in pathogenesis of acute pancreatitis induced by closed
      duodenal loop in rat, but other factors may play more important roles.

PMID- 1345385
TI  - Intraductal papilloma and papillomatosis.
AB  - The benign papillary neoplasms of the breast are still controversial topics in
      general surgery. There are two forms of the benign papillary lesions, solitary
      intraductal papilloma and multiple intraductal papilloma. These disorders are
      very rare and their clinical behaviour is different in each case. In this study,
      two cases of the multiple intraductal papilloma are presented and clinical
      findings and surgical therapy are discussed.

PMID- 1345384
TI  - Effect of truncal vagotomy and pyloroplasty on rat gastric mucosal H,K-ATPase and
      HCO3-ATPase activities.
AB  - The effect of truncal vagotomy and pyloroplasty on rat gastric mucosal H,K-ATPase
      and HCO3-ATPase activities was studied 15 and 30 days past the operation. A
      significant decrease in gastric body mucosal H,K-ATPase activity occurred 15 days
      after vagotomy, compared with pyloroplasty (p < 0.05) and non-operated control
      rats (p < 0.01). A recovery in the enzyme activity on the 30th postoperative day
      occurred. Gastric body and antral mucosal HCO3-ATPase activity was significantly
      (p < 0.01) decreased 15 and 30 days after vagotomy and pyloroplasty, compared
      with pyloroplasty controls. The observed changes in gastric mucosal H,K-ATPase
      and HCO3-ATPase activities after vagotomy reflect the decrease in gastric acid
      secretion, as well as the possible changes in mucosal bicarbonate secretion and
      acid-base status. A gradual recovery in mucosal H,K-ATPase activity after
      vagotomy may occur.

PMID- 1345386
TI  - Case report of a patient with recurrent fibrosarcoma of the thoracic wall.
AB  - A case of a patient with recurrent chest wall fibrosarcoma is presented who had
      her original tumour removed 12 years earlier. The histology of the primary lesion
      was missed for a localized fibrous mesothelioma. Author reviews the pathology and
      management of soft tissue tumours of the thoracic wall.

PMID- 1345387
TI  - Biomechanical aspects of femoral stem anchoring during total hip replacement.
AB  - Stem instability is the major cause of complications following total hip
      replacement. To prevent its onset, the authors based their method on Wolff's law
      of bone transformation. Of the known prostheses, the straight-stem one fitting
      best to the shape of medullar cavity was chosen and by its sagittal enlargement
      in three different sizes a new stem collection was designed. Stems providing the
      closest fit to the medullar cavity were selected by computer-assisted adjustment
      to three-directional X-ray pictures. The principle seems to be supported by
      preliminary results.

PMID- 1345389
TI  - Conservative surgical management of pancreatic injuries.
AB  - Seven cases of pancreatic injuries of various severity ranging from grade I to
      grade IV treated by closed tube drainage are presented. Only one patient
      developed pancreatico-duodenal fistula postoperatively which was managed
      conservatively and closed within four weeks. Simple drainage is a satisfactory
      method in the treatment of pancreatic injuries.

PMID- 1345388
TI  - The "Mannit-Ceftriaxon" preparation for elective colorectal surgery.
AB  - Authors report their experiences with evaluating the clinical course of 45
      patients undergoing elective colorectal surgery. Patients were divided into three
      groups, depending on the type and method of preparation to operation. The 140
      patients in the first group received according to the "traditional" preparation
      purgatives, enemas, and mycerine + metronidazole prophylaxis. The preparation of
      the 160 patients involved in the second group was performed by giving mannit
      solution (10%) orally 12 hours prior to surgery, and a single dose of 2 g
      ceftriaxon (Rocephin, Hoffman-La Roche) intravenously 2 hours preoperatively. The
      preparation for the 150 patients enrolled into the third group was done also by
      giving mannit solution orally, and for antibiotic prophylaxis 2 g ceftriaxon was
      given intravenously as in the second group, but an additional 500 mg
      metronidazole was also given at the same time as the ceftriaxon intravenously.
      The evaluation of the cases proves, that the mannit + ceftriaxon method warrants
      satisfactory protection for colorectal surgery, and the necessary time interval
      is only 12 hours. The rate of septic complications and septic death was higher in
      the first, traditionally pretreated group, than in the other two. The CTX +
      metronidazole combination used in the third group was not superior to the
      administration of ceftriaxon alone.

PMID- 1345390
TI  - The effects of cholelithiasis and cholecystectomy on gastric emptying.
AB  - In this clinical study, four groups, each consisting of 12 patients are
      established to determine how gastric emptying is influenced in cholelithiasis
      with accompanied flatulent dyspepsia and the relationship of symptoms and gastric
      emptying after cholecystectomy. 1. group: healthy people, 2. group: patients with
      dyspeptic cholelithiasis, 3. group: patients who have no dyspepsia after
      cholecystectomy, 4. group: patients whose dyspepsia is continued after
      cholecystectomy. Groups are compared according to solid phase gastric emptying
      scintigraphies performed with Tc 99m sulfur colloid bound with scrambled eggs.
      Gastric emptying delayed in second (p < 0.001) and fourth (p < 0.005) groups
      postprandially and not differed in the third group (p > 0.005). These results
      demonstrate that dyspepsia, in cholelithiasis and persisting after
      cholecystectomy have a close relation with delay in gastric emptying.

PMID- 1345391
TI  - Experimental salvage of the spleen. A combined technique of cryosurgery and
      tissue sealant.
AB  - The goal of this investigation has been to improve the safety of intra- and post
      operative haemostasis in splenic lesions by a combined technique of tissue
      freezing followed by the application of collagen fleece and fibrin glue in an
      animal study. The progression of healing was observed after different periods of
      time. Grade II lesions were set on the spleens of 15 pigs. The wounds were frozen
      for 1 m at -60 degrees C with a cryosurgical probe and afterwards sealed with
      fibrin glue and collagen fleece. In every case, complete haemostasis was achieved
      intraoperatively. The spleens of 3 animals each were examined microscopically
      after 2 days, 1, 2, 5 and 6 weeks, respectively. A visceroperitoneal adhesion was
      observed in only 1 spleen and u-shaped viscerovisceral adhesions in 5 spleens.
      Superficial coagulation necroses were observed only in specimens removed after 2
      days and 1 week, respectively. Complete and safe haemostasis followed by
      acceptable subsequent healing was achieved using this combined technique.

PMID- 1345392
TI  - Loco-regional renewal of malignant melanomas. I. Local recurrence satellites and
      in-transit nodes.
AB  - 183 patients with malignant melanoma treated during the period 1972-1987 were
      studied for the incidence of loco-regional metastasis. All cases were followed up
      for 5 years following initial treatment. In the "high risk" groups of patients-
      the setting being based on well-known prognosticators such as tumour invasion,
      thickness, clinicopathological type and anatomic site--there were significantly
      more recurrences (p < 0.01) than in the patients with thin lesions. About 91 per
      cent of the recurrences--except pure model ones to be discussed in an other paper
      -were discovered within 30 months following tumour excision. Wide excision in
      itself had no effect upon frequency and incidence of loco-regional renewal. While
      local recidivae were sufficiently controlled by simple re-excision, most of the
      "in-transit" metastases need an additional regional lymph node dissection because
      of the increased rate of micrometastases in the lymph nodes. Survival and
      treatment modalities are also discussed.

PMID- 1345393
TI  - Loco-regional renewal of malignant skin melanomas. II. Regional lymph node
      metastases and regional recurrence.
AB  - The strategy of surgical therapy to treat regional disease in melanoma remains
      still controversial. The author analyzed 154 of 183 melanoma patients, who could
      be studied for the usefulness of surgery directed against regional tumour spread.
      Radical tumour excision combined with elective lymph node dissection (E+eRND) in
      medium or high risk tumour patients was found superior to therapeutic dissection
      (tRND) inasmuch 5-year-survival rates were significantly different (p < 0.001).
      Life expectancy seemed to be further impaired when postdissectional renewal
      appeared following tRND (5-year-survival rates 31.8 per cent --> 12.7 per cent)
      or tRND was incomplete.

PMID- 1345394
TI  - Surgical male contraception.
AB  - After giving a short account on the possible ways of male contraception, the
      authors outline the administration of surgical sterilization and its professional
      follow-up based on their own experience. Their suggestions concerning legal
      regulations aim, on the one hand, at the extension of the topic, on the other
      hand at supporting the specialists interested in surgical contraception.

PMID- 1345395
TI  - Myasthenia gravis: prognostic significance of clinical data in the prediction of
      post-thymectomy respiratory crises.
AB  - Medical records of 170 patients who had undergone thymectomy for myasthenia
      gravis were reviewed from the point of view of respiratory disturbances. In the
      group of patients requiring mechanical ventilation for over 24 hours after
      operation the incidence of high preoperative cholinesterase inhibitor intake,
      severe bulbar symptoms and severe myasthenia gravis with anamnestic respiratory
      crisis and cardiorespiratory disease were much higher than in the group of
      patients who could have their trachea extubation within 24 hours. The presence of
      a thymic tumour, patients' age over 50 years and the so-called precrisis have
      revealed differences between the two groups, while the patient groups were
      identical in mean age, duration of myasthenia gravis and sex distribution. The
      above clinical data are recommended to be considered in the evaluation of the
      need for postoperative mechanical ventilation or extubation and preparation of
      preventive tracheotomy.

PMID- 1345396
TI  - Experimental animal-modelling of Indiana type continent urinary reservoir.
AB  - To gain experience in animal experiments prior to introduction in human practice
      is fundamental in our opinion. Apart from achieving practice in operative
      technique, analysing and possible avoiding unnecessary complications might be the
      ethical positive consequences of this practice. On the other hand, functional
      tests prior to human use will be possible, and as it has been demonstrated in our
      present study, modifications of technique might be the result of animal
      experiments.

PMID- 1345397
TI  - Intraoperative estimation of liver blood flow in man.
AB  - The intraoperative measurement of the afferent circulation of the liver, namely
      the hepatic artery flow and portal venous flow was carried out upon 14
      anaesthetized patients having carcinoma of the splanchnic area, mainly in the
      head of the pancreas, by means of transit time ultrasonic volume flowmeter. The
      hepatic artery flow, portal venous flow and total hepatic flow were 0.377 +/-
      0.10; 0.614 +/- 0.21; 0.992 +/- 0.276 l/min, respectively. The ratio of hepatic
      arterial flow to portal venous flow was 0.66 +/- 0.259. There was a sharp,
      significant increase in hepatic arterial flow (29.8 +/- 6.1%, p < 0.01) after the
      temporary occlusion of portal vein, while the temporary occlusion of hepatic
      artery did not have any significant effect on portal venous circulation. The
      interaction between hepatic arterial flow and portal venous flow is a much
      disputed question, but according to the presented data here, it is
      unquestionable, that the decrease of portal venous flow immediately results a
      significant increase in hepatic artery circulation.

PMID- 1345398
TI  - Posterolateral lumbar spine fusions: private v. NHS. Comparative, preliminary
      study.
AB  - In the present study comparative evaluation has been carried out between the
      groups of patients (31 in each group, private and National Health Service)
      treated by posterolateral lumbar spine fusion for mechanical lower back pain. The
      same surgical team was involved in the treatment. The patients were evaluated
      independently at an average follow-up of more than three years in each group. The
      acceptable clinical results (good and fair) showed a remarkable difference
      between the two groups, with the private group enjoying the better outcome. The
      difference of final outcome was analyzed by looking at the waiting time for
      surgery, the social classification of the patients and the provision of state
      benefit for disability.

PMID- 1345399
TI  - Role of surgery in the prevention and correction of hip subluxation and
      dislocation in cerebral palsy.
AB  - Forty-three patients (80 hips) were available for clinical and radiological
      follow-up. These patients underwent adductor tenotomies separately or in
      combination with other procedures on the hip, with or without proximal femural
      correction. The range of abduction in all hips before surgery was 40 degrees or
      less, and in 54 hips combined with flexion-contracture (10 degrees-50 degrees).

PMID- 1345400
TI  - [Expressed emotion: past, present, future].
AB  - Expressed Emotion (EE) proved to be the best single predictor of relapse in
      schizophrenia in 1972. Since then, studies on EE were oriented in three
      directions: Replication of the original study in different countries, improvement
      of the methodology and clinical applications. The analysis of different key
      studies shows that EE is a powerful predictor factor, although it is influenced
      by other variables such as culture.

PMID- 1345401
TI  - Enduring negative psychological characteristics of male and female step-children
      toward the step-parent.
AB  - Many divorced people remarry, and if either one or both of the remarried partners
      has a child or children from a former marriage, then the youth need adjust to not
      only the new marital structure, but to the new step-parent as well. The present
      research was conducted to determine: (1) enduring negative psychological
      characteristics of male and female step-children toward the step-parent, and (2)
      a comparison of the similarities and/or differences of each. Results suggested
      ten of the most frequently stated variables of both subject groups, similarities
      or significant differences between them by subject status, and their relevancy to
      the step-child-step-parent relationship.

PMID- 1345402
TI  - [Outcome of 89 psychiatric emergencies managed by 3 mental health centers in an
      emergency service].
AB  - This paper deals with the assessment after 2 years of the outcome of 89
      psychiatric emergencies taking in charge in Saint-Luc hospital's (Brussels)
      emergency room, by 3 community mental health services. After the triangulation of
      the demand, in the emergency room, 91% of the patients go to the community mental
      health service. In 92.5% of cases, the crisis intervention is carried out by the
      same therapists they met in the emergency room with the collaboration of other
      members of the outpatient team. Crisis interventions are brief (less than 3
      months) in 50% of cases, less than 1 years in 11.5% of cases and lead in 35% of
      cases to long-term in charge (more than 2 years: psychiatric and social follow
      up).

PMID- 1345404
TI  - [The elderly subject and social violence: the body as a factor in communication].
AB  - The social inferiority of an elderly person stems from his physical inferiority-
      actual or alleged but always possible. And yet this "inferior" body is
      paradoxically hypertrophic: at first it masks the person, then takes up its space
      until it negates it. Hence, an elderly person is not only a body but a lonely
      body. In his relations with other people, his body becomes a receiver, a
      receptacle and a source of communication. Social violence underlies relations
      with elderly people: such violence may be deceptive, widespread and continuous
      or, on the other hand, manifest, episodic and conspicuous. In the first case it
      may be a way of assigning subalternate roles to them in relation to the
      efficiency expected of them or a way of mythologizing their condition as one of
      pseudo-happiness. In the second case is generally relates to assaults, thefts,
      bag-snatching, etc. In any case, however, communication with them entails
      violence: their body perceives this and reacts to it. This is why their body's
      language is violent: their body cries out, it is stunned and it is acted upon
      (even--and unavoidably--in relations with a therapist).

PMID- 1345403
TI  - An open multicentre study to evaluate the efficacy and tolerance of fluoxetine 20
      mg in depressed ambulatory patients.
AB  - In this study, 544 out-patients suffering from depressive disorders were enrolled
      in 6 weeks open study with fluoxetine 20 mg. A statistically significant decrease
      of the Hamilton Rating Scale for Depression (HRS-D) score is observed during
      treatment. All individual item HRS-D scores and in particular suicidal ideation,
      sleep disturbances and anxiety showed the same improvement. Side-effects were
      carefully recorded and presented a lower incidence rate than in other studies.
      New issues in methodology management concerning ambulatory studies are discussed.

PMID- 1345405
TI  - [No hypofrontality in schizophrenia demonstrated by positron emission
      tomography].
AB  - We studied cerebral glucose metabolism, using Positron Emission Tomography (PET)
      and (F-18) fluorodeoxyglucose, in 15 young schizophrenic patients compare to 15
      age-matched healthy volunteers. The PET investigation was made in a quiet room
      with a dimly light. Each subject remained in a supine resting state with eyes
      closed. Results failed to demonstrate any differences in glucose utilization
      between schizophrenic patients and control subjects, as far as absolute or
      relative, left and right values are concerned. Besides, variability of metabolic
      values was significantly higher in schizophrenics than in controls.

PMID- 1345406
TI  - [Cognitive-behavioral approach to alcoholism: preliminary report of the
      realization of a therapeutic group].
AB  - The heterogeneity of alcoholic patients has lead alcohologists to find specific
      treatments for them. The cognitive-behavioural approach enables recognition of
      the cognitive and communicational distortions disclosed by these patients. This
      approach attempts to correct these distortions by training social skills. In
      accordance with this orientation, we have organised a therapeutic group for
      alcoholic patients. We have estimated how much patients appreciate this approach
      and how they expect it to change their drinking behaviour. Thirty-five alcohol
      dependent patients have agreed to take part in three groups during their stay in
      hospital for detoxification. Each session deals with one of the following themes:
      "reproach & refusal", "request & emotions" and "relapse". The rating is assessed
      through a self-administered questionnaire. The appreciation of the method is very
      good for all measured parameters, and 76% of the patients consider it can help
      them.

PMID- 1345407
TI  - [Which abstinence in alcohol problems?].
AB  - Examining the place of abstinence in alcoholism, the authors review the different
      tendencies in recent literature (total abstinence, controlled drinking,
      responsible drinking). According to the type and severeness of these problems,
      different approaches are presented in the frame- work of family therapy. Through
      the development of a clinical case, the authors illustrate the interest of
      prescribing compulsory abstinence within the context of voluntary
      hospitalization, family and individual psychotherapy.

PMID- 1345408
TI  - [Therapy for couples in their sixties].
AB  - There is small interests in marital therapy for 60 years and more, for which a,
      at least, partially specific approach seems us necessary. After reviewing the
      weak literature regarding this topic the authors present six marital therapy in
      this age group. They propose in their conclusions a five points model of care:
      brief taking in charge or "coevolution", psychiatric approach, "problem solving",
      specific crisis of this ages, speaking about sexual life.

PMID- 1345409
TI  - Controlled comparison of RO 11-1163 (moclobemide) and placebo in the treatment of
      depression.
AB  - Moclobemide was compared to placebo in two parallel groups of depressed patients,
      in a multicenter randomized, double-blind study of six weeks treatment duration.
      Forty seven patients participated in the study: 23 received moclobemide (flexible
      dose 300-600 mg/day) and 24 placebo. They were evaluated weekly for efficacy and
      tolerability. Moclobemide was more efficacious than placebo as judged by analysis
      on the total score on the Hamilton depression scale (p < 0.05) and by the overall
      assessment of efficacy (p < 0.01). Moclobemide was also more effective than
      placebo in the subgroup with neurotic depression (p < 0.05). In addition, the
      number of patients prematurely terminating treatment for inefficacy, was higher
      in the placebo than in the moclobemide group (12 versus 2, p < 0.01). The number
      and the severity of side-effects tended to be slightly greater in the moclobemide
      than in the placebo group, but this did not reach a level of significance.
      Cardiovascular tolerability was good in both treatment groups. No hypertensive
      crisis was reported. Hematology, clinical chemistry and urine analysis were not
      affected by the treatment in any clinically significant fashion.

PMID- 1345410
TI  - [Effects of hydroxyzine on attention and memory in elderly subjects].
AB  - A single intake of hydroxyzine 25 mg was compared to placebo, and lorazepam 1 mg
      as a verum, in a double-blind, triple-crossover trial. Each of the 12 elderly
      volunteers was tested on three different days, once under each condition. At 2.5
      hours after drug intake they were assessed or reassessed for attention, immediate
      and delayed (30') memory, cognitive ability and feelings of anxiety and fatigue.
      Some subjects mentioned a minimal sedation under hydroxyzine 25 mg and under
      lorazepam 1 mg, but only hydroxyzine preserved memory and attention, while
      lorazepam caused clear deficiencies in memory recall.

PMID- 1345411
TI  - Risks of sarcomas of the breast among women with breast augmentation.

PMID- 1345412
TI  - Mollaret's meningitis and herpes simplex virus type 1.

PMID- 1345413
TI  - Effectiveness of air bags.

PMID- 1345414
TI  - Immunologic purging of marrow assessed by polymerase chain reaction.

PMID- 1345415
TI  - Alzheimer's disease and beta-amyloid.

PMID- 1345416
TI  - I'm proud to be a nurse.

PMID- 1345418
TI  - An international perspective from New Zealand on healing touch.

PMID- 1345417
TI  - Oral anticoagulants. Mechanism of action, clinical effectiveness, and optimal
      therapeutic range.

PMID- 1345420
TI  - [The practice of electroconvulsive therapy: current contribution. II.-
      administration and evaluation of treatment].
AB  - In this second of a two-part review about electroconvulsive therapy (ECT)
      practice, the author highlights recent advances in ECT course management with a
      special emphasis on pre-ECT evaluation, treatment procedures, evaluation of
      outcome and post-ECT course. Pre-ECT assessment should include an evaluation of
      medical risk factors and concomitant use of psychotropic or medical agents have
      to be reconsidered. Practical and technical aspects of stimulus administration
      and their relationships with post-ECT cognitive disabilities are then presented.
      Monitoring of treatment response and cognitive changes during ECT course is also
      discussed as well as post-ECT pharmacotherapy maintenance or continuation ECT.

PMID- 1345419
TI  - Rheumatic heart disease in Africa.
AB  - Rheumatic heart disease continues to be relatively common in many parts of
      Africa, predominantly affecting young people. Special attention should be given
      to its prevention by the inexpensive methods that have proved effective
      elsewhere, and to this end assistance should be provided by the international
      community.

PMID- 1345421
TI  - [Current psychoanalytic observations on dreams].
AB  - What is a dream from a psychoanalytical point of view? Freud first contemplates
      the fulfillment of the wish (1900), then the compulsion to repeat (1920) and
      finally the benefit of pleasure (1925). Following J. Lacan, a function of coding
      can be brought out: the dream substitutes the picture translated enjoyment of the
      sign from traumatic reality. Thus, the dream dreamt is not a message but a means
      of enjoyment of the unconscious.

PMID- 1345422
TI  - [Psychiatric commitment and current legislation of 26 June 1990 relative to
      mentally ill persons].
AB  - A study on the psychiatric confinements in the Walloon region in the year 1984
      allows to define the patient's psychopathology and the context of the requests.
      The new law of the 26 June 1990 relating to the protection of the mentally ill
      person will probably be used mostly in such situations. Its conditions of
      implementation, positive aspects and the difficulties it could create are
      detailed.

PMID- 1345423
TI  - [The adolescent in general psychiatry].
AB  - Ever since the works of anti-psychiatry and the bringing out of the danger of
      trying to master the adolescent, we have been made aware of a certain iatrogenic
      pathology. What is less known are the identification risks which exist between
      the young patient and the mentally-ill person. This identification can be
      imaginary, but it always runs the risk of becoming symbolic and opening up the
      way to chronification. So it would seem to us to be important to promote a
      special setting for adolescents.

PMID- 1345424
TI  - [HIV infection in women. Psychological and somatic obstacle].
AB  - We consider the word "impediment" in the meaning of what compels someone, makes
      someone feel uncomfortable. What are the consequences/implications of
      seropositivity for the woman in her sexual life, in her motherhood and how does
      she then cope with it? The following clinical observations account for the
      suffering induced by seropositivity and the diversity of the processes
      spontaneously set by HIV-infected women in their sexual life. To answer that
      suffering, the commonly used psychotherapeutical approach is a palliative one.

PMID- 1345425
TI  - [Integrated care of HIV-seropositive patients: liaison psychiatry revisited].
AB  - Psychiatric, psychologic and psychotherapeutic care of HIV patients is integrated
      inside a specific medical institution. The psychological representations that
      AIDS mobilizes pervade the intense medical relationship between internists,
      nurses and the HIV patients. This relationship becomes the central node for the
      differentiation of psychologists and psychiatrists function inside the team. We
      propose here three different functions: the bio-psycho-social integrated care of
      the patients; the "binding" of psychical representatives inside the HIV patient
      who is in a death process; the binding of the representatives disseminated inside
      the medical team by the patient.

PMID- 1345426
TI  - [AIDS, burnout and fear of knowing. Dialectic observations for the benefit of
      clinical psychology and liaison psychiatry].
AB  - A review of the literature regarding burn-out provide a sample of specific
      variables that describes the phenomenon. This could potentially leads to the
      emergence of a set of actions intending to facilitate the task of health workers
      (at least if personnel managers pay it attention). However, it does not preclude
      the risk of burn-out, neither does it explain its nature. This syndrome seems to
      be more prevalent in certain medical departments and it occurs to us--through
      careful listening to health workers and AIDS patients--that, to learn about
      something that affects health workers, we have to ask patients, supposing they
      were in the first line. We then realized that knowledge makes distress.

PMID- 1345427
TI  - [AIDS: challenge to liaison psychiatry. Various expectations by clinicians
      concerning liaison psychiatry].
AB  - Interdisciplinary group work could be conceived as shared common abilities in
      order to provide a global management of diseases. In this regard, psychologists
      should assumed several tasks: to advise on patient's psychological resources to
      keep them less anxious or more cooperative, to humanize hospital and death, to
      prevent burn-out. This does not mean a management of the illness, but a careful
      listening to help patients to find a meaning to what they are living. The aim
      should not to harmonize different skills but to define each other place
      (physician, social worker, nurse, psychologist...) concerning queries that
      involve us and that wonder us about life, health, sexuality, love, the way we
      take risks.

PMID- 1345428
TI  - [Prevalence of human immunodeficiency virus infection in a psychiatric population
      in Central Africa].
AB  - In an African population of 292 women, hospitalised for psychiatric reasons, the
      seropositivity for HIV was clearly found higher than in the general corresponding
      population; this was particularly significant for first hospitalisations;
      furthermore, the seropositivity became twice as high in the group hospitalised
      several times. The HIV, known for neurotropism, seems responsible for a psychic
      fragility factor, favorising psychiatric breakdowns as well as their recurrences.
      No specific psychiatric diagnosis appears to be related to the seropositive
      patients. This study suggest that psychiatric breakdowns are already favoured in
      the period preceeding immunodeficiency symptoms (AIDS or ARC).

PMID- 1345429
TI  - Is REM latency a dying concept?
AB  - Twenty years have passed since the discovery that a shorter REM latency was one
      of the most significant biological correlates of depression. Its diagnostic and
      clinical discriminant power have been challenged both in terms of sensitivity and
      specificity. The present paper is a review of the relevant literature of these
      years until the present time and has focused on (a) technical problems concerning
      the REM latency, (b) its diagnostic value, (c) the state or trait meaning, (d)
      the use of the cholinergic and aminergic challenge, (e) the effects of
      treatments. A summary of (f) the effects of age and (g) REM sleep propensity as a
      cycle phenomenon have been added. The conclusions tend toward considering REM
      sleep disorders as an expression of a multiple circadian cycle abnormality,
      globally seen as a trait, itself highly correlated with psychiatric pathology and
      especially with affective disorders.

PMID- 1345430
TI  - Cholinergic and noradrenergic neurotransmission: impact on REM sleep regulation
      in healthy subjects and depressed patients.
AB  - The reciprocal interaction model of NonREM- and REM sleep regulation suggests
      that the cycling alternating pattern of Non-REM- and REM sleep is under the
      control of noradrenergic/serotonergic and cholinergic neuronal networks. This
      model was tested in healthy humans by administration of cholinergic
      agonists/antagonists and noradrenergic antagonists prior to or during sleep.
      Cholinomimetics like physostigmine, RS 86 and galanthamine provoked an earlier
      onset of REM sleep, whereas subchronic treatment with scopolamine, a cholinergic
      antagonist, only led to a heightening of REM density. Simultaneous administration
      of noradrenergic antagonists with a cholinergic agonist did not provoke a more
      pronounced REM sleep advance. Comparative studies with the cholinergic agonist RS
      86 in depressed patients, schizophrenic patients and patients with other
      psychiatric disorders revealed the most pronounced REM sleep response in the
      depressed group. The REM sleep response to cholinergic stimulation in depression
      did however not predict the treatment response to a differential-therapeutic
      strategy.

PMID- 1345431
TI  - Naps and depression.
AB  - In healthy subjects, napping has often been seen as an "abnormal" form of sleep,
      while sleep has been considered as a necessary feature of life. Social and
      cultural biases influence the occurrence of napping behavior. However, several
      observations indicate the presence in man of a two per day modulation of sleep
      propensity. On the other hand, alterations of nocturnal sleep have been widely
      described in affective disorders, but little is known about the presence of
      daytime sleep in depressed patients and the possible effect of daytime sleep
      episodes on nocturnal sleep. Some attempts to characterize daytime sleep in
      depression are reviewed. A recent study based on continuous polygraphic
      recordings indicate that napping occurrence appears to be similar in depressed
      patients than in control subjects. However, naps structure and organization were
      different in depressed patients in comparison to controls. Napping seems thus to
      be more prevalent in depressed patients than previously assumed. Possible effects
      of naps on mood, alertness in depressed patients remains to be explored.

PMID- 1345432
TI  - Polysomnographic characteristics in recurrent brief depression: a comparative
      study with major depression and controls.

PMID- 1345433
TI  - TSH response to TRH stimulation in major depression: relationship to clinical and
      sleep EEG variables.

PMID- 1345434
TI  - Rhythmic body movements in REM sleep: a case-report.

PMID- 1345435
TI  - The effects of 5-HT2 antagonism on slow wave sleep in major depression:
      relationship with clinical aspects.

PMID- 1345436
TI  - [Contribution of neo-electroencephalography in adult functional and psychiatric
      disorders].
AB  - Two comparative studies of the basic activity at rest, with closed eyes taken in
      conventional EEG and analysed in Neo-EEG are carried out in adults showing
      functional or psychiatric disorders. The first open study involves 18 subjects
      suffering from a affection called "neurodystony" and 24 depressed subjects. The
      second study made in double-blind compares the results of the conventional EEG
      with the Neo-EEG in 19 depressed patients, 28 alcoholic patients and 26 psychotic
      patients. The Neo-EEG discloses abnormalities in about 60% of the cases when the
      conventional EEG is normal. The conventional EEG as well as the Neo-EEG diagnose
      a greater number of low voltage in alcoholic subjects and clear abnormalities in
      psychotic subjects. Low voltage is never detected in psychotic patients. In
      depressives, the Neo-EEG shows about 65% of abnormalities of which an asymmetry
      of the basic frequency in the center of the two hemispheres when they are
      analysed separately. That asymmetry develops in parallel with the clinical state.
      The asymmetry is also found in psychotic patients. In nervous or neurodystonic
      subjects, the Neo-EEG only discloses 25% of abnormalities. The Neo-EEG appears as
      an easy method, able to detect dysfunctions which cannot be disclosed with the
      conventional EEG and useful to follow their developments. Moreover, the result of
      this technique brings to the fore abnormalities not detected with the
      conventional EEG: this eventually leads to prescribe other therapies than those
      initially considered.

PMID- 1345437
TI  - [Resectoscopic endometrial ablation in the treatment of recurrent, dysfunctional
      menometrorrhagia: our experience].
AB  - Advances in hysteroscopic surgery provide additional options to hysterectomy for
      the treatment of dysfunctional uterine bleeding resistant to medical therapy and
      multiple curettages. Two techniques are now available: (a) Resectoscopic
      endometrial ablation. (b) Electrocoagulation or laser photovaporisation of
      endometrium. 52 patients underwent resectoscopic endometrial ablation at the
      Gynaecology Department of Parma University from January 1991 to April 1993. All
      patients suffered from dysfunctional uterine bleeding without atypical histologic
      findings on endometrial biopsies and had a normal shaped uterine cavity. 41
      patients were subsequently contacted for follow-up. Follow-up period ranged from
      a minimum of 3 months to a maximum of 24 months. 78.1% of the patients reported a
      satisfactory outcome (amenorrhea or decreased menstrual flow). No operative
      complication occurred. Post operative complications included one case of
      hematometra. CONCLUSIONS: resectoscopic endometrial ablation is an advantageous
      technique but our follow-up period is relatively short and long term sequelae
      have yet to be determined.

PMID- 1345438
TI  - [Pregnancy and breast-feeding: developmental stages of mother-child bonding].
AB  - Several authors, confronting the mother-child relationship during pregnancy and
      breast-feeding, talk about an uterine and extra-uterine symbiosis. In this way,
      one bypasses the fact that the so called unions end with the processes of
      separation constituted by the birthing/birth (by the termination, that is to say,
      of the first maternal nurturing (that of placenta) as well as by the termination
      of the second maternal nurturing (that of the individual breast-feedings). The
      careful observation of these unions demonstrates that they coexist and they imply
      equilibrium through the processes of separation that not only allow a partial
      autonomy of the developments of mother and child, but also make room for the
      detachments represented by the birthing/birth and by the end of the individual
      breast feedings. The author is trying to illustrate some physiological and
      pathological equilibrium between these tendencies towards reciprocal dependence
      and reciprocal mother-child autonomy.

PMID- 1345439
TI  - [Efficacy of mini-TENS in the treatment of primary dysmenorrhea].
AB  - Recent knowledge on the pathogenetic mechanisms which are thought to be
      responsible for primary dysmenorrhea in most young females allow us to abandon
      old therapeutical approaches for several medical solutions with high
      effectiveness rates. But a number of patients remain for whom these treatments
      are not suitable or not effective. Mainly for these patients, today we can offer
      a valid alternative, a new kind of electroanalgesy, TENS, now easier to use owing
      to the miniaturization of the machine. In fact, in two groups of patients
      resistant or insensitive to modern medical therapies, we obtained good analgesia
      during the menstrual period, without important side effects and with high
      compliance by the patients.

PMID- 1345440
TI  - Video technology. Basics for perioperative nurses.

PMID- 1345441
TI  - APACPH Public Health Recognition Award 1994. Professor Kazue Kimura McLaren
      Leadership Achievement Award. Dr. U Ko Ko, Director, Regional Office of Southeast
      Asia, World Health Organization, New Delhi, India.

PMID- 1345442
TI  - Dr. U Ko Ko's acceptance speech for the "Professor Kazue K. McLaren Leadership
      Achievement Award" Ceremony--Saturday, 18 December 1993, Bangkok, Thailand.

PMID- 1345443
TI  - A study on the isolation of aflatoxin-producing strains from agricultural
      products in Korea.
AB  - In order to isolate aflatoxin-producing strains from agricultural products in the
      Youngnam district of Korea, rice, barley, unhulled barley, corn, soybean, Meju
      (soybean paste), peanut, and soil samples were collected from markets or homes.
      From the 347 samples, 280 strains of Aspergillus spp. were isolated. As a result
      of screening by thin layer chromatography (TLC), 29 strains showed fluorescent
      spot and four strains had the same Rf values as those of standard aflatoxins. The
      percentage of contamination of aflatoxin-producing strains was 1.4%. The four
      strains were classified as the Aspergillus flavus group by the examination of
      characteristics and morphology.

PMID- 1345445
TI  - Prevalence of cardiovascular diseases in rural area of Hmawbi and urban Yangon
      city.
AB  - With improvements in life expectancy and as more and more people have access to
      modern medicine, non-communicable diseases are emerging as a health problem in
      both urban and rural communities in Myanmar. Of all non-communicable diseases,
      cardiovascular diseases (CVD) are known to be the major health problem. Since
      many studies that have been conducted in both developed and developing countries
      have shown a difference between rural and urban communities with regard to
      cardiovascular diseases, our study had the objective of finding out the
      prevalence of ischemic heart disease, hypertensive heart disease and rheumatic
      heart disease in a rural and urban community. The risk of obesity and smoking in
      the occurrence of CVD was also studied. A cross-sectional survey was conducted in
      three urban townships of Yangon City (Sanchaung, Latha and Pabedan) and one rural
      township of Hmawbi. The results showed that CVD were a health problem in both the
      urban and rural communities. Coronary heart disease was seen to be more prevalent
      in the urban townships than in the rural Hmawbi Township, but hypertension (HT)
      and rheumatic heart diseases (RHD) were more prevalent in the rural township of
      Hmawbi. Obesity which has been blamed as the major risk factor for CHD and HT in
      the developed countries was not found to be a risk factor in the study townships,
      but smoking was.

PMID- 1345444
TI  - Prevalence of goiter in a rural community in Sri Lanka.
AB  - The prevalence of goiter in a rural community was determined in a defined
      geographical area, namely, the Hindagala Community Health Project (HCHP). In this
      area which is divided into six Public Health Midwife (PHM) areas, the mean
      altitude varies from 450 to 775 meters. The house-to-house goiter survey
      conducted by the trained field health staff covered 70% of the population. The
      total goiter prevalence was 7% while the prevalence of visible goiter was 2.8%.
      The goiter prevalence was higher in the females than in the males at all age
      groups. Among males, the prevalence was highest in the school-going age group 6
      18 years, while among females the highest prevalence was in the early
      childbearing period of 19-34 years. Further, an increasing trend in the
      prevalence was observed with increase in mean altitude of the PHM area.
      Correlation between community prevalence and age-sex specific prevalence gave the
      best relationship with the 6-18 year age group and a regression equation to
      predict the community prevalence from the prevalence in the school-going age
      group is presented.

PMID- 1345446
TI  - Cancer in the elderly: a prospective study among Hawaiian Japanese men.
AB  - In the United States, little has been done to compare the cancer risk of elderly
      subjects, aged 65 and older, with that of younger subjects. Although the elderly
      constitute only 12% of the population, they are diagnosed with more than 50% of
      the cancers. The study consisted of 7,783 Japanese-American men, born from 1900
      1919 and examined from 1965-1968. During 154,000 person-years of follow-up, 1,478
      incident cases of cancer were identified. The incidence rate of cancer was high
      among the elderly (142.7 per 10,000 person-years) compared with younger subjects
      (48.2 per 10,000 person-years), yielding a significant (p < 0.05) rate ratio of
      3.0. Of the site-specific cancers, prostate cancer showed the highest rate ratio
      of 7.0, followed by oral, stomach, lung, and colon cancer. In addition, the five
      year age-specific rates for stomach and colon cancer rose directly with age. A
      similar pattern was also observed for lung and prostate cancer in men before age
      80, but the rates declined thereafter. The findings from this study suggest that
      the reduction in risk for cancers of the prostate, oral cavity, stomach, lung,
      and colon must be viewed as a major goal for improving the public health in the
      elderly population.

PMID- 1345447
TI  - Diet and blood nutrient correlations with ischemic heart, hypertensive heart, and
      stroke mortality in China.
AB  - Though major differences exist in subcategory mortality levels, cardiovascular
      disease remains a leading cause of death among both Asian Chinese and Westerners.
      This paper examines the possible relationship between cardiovascular mortality
      and biochemical, diet and lifestyle factors based on two surveys in China.
      Statistically significant associations indicate five variables negatively
      correlated: molybdenum, oleic acid, liquor consumption (males), legumes, and age
      at first pregnancy with ischemic heart disease; molybdenum, oleic acid (females)
      and age at first pregnancy with hypertensive heart disease; and legumes and age
      at first pregnancy with stroke. Five variables were positively correlated:
      triglycerides and herpes antibodies with ischemic heart disease; salt and
      phosphorus (females) with hypertensive heart disease; and only albumin (males)
      with stroke. Some findings confirm those observed in the West (salt,
      triglycerides, herpes, legumes, oleic acid, and liquor), but molybdenum and age
      at first pregnancy have not been emphasized previously. Still others significant
      in the West have not been observed here, such as cholesterol and smoking.

PMID- 1345448
TI  - Nutrition promotion: the role of monitoring physical growth.
AB  - Growth monitoring has been included as one of the basic strategies for child
      survival. In this paper, the rationale for this is reiterated both for individual
      as well as population nutritional surveillance. Methods for and approaches to
      growth monitoring are described. In addition, potential problems in implementing
      growth monitoring projects and interpreting the results are discussed. Despite
      its lack of sensitivity and specificity as a diagnostic tool, its advantages in
      terms of low cost, simplicity, reliability and social acceptability justify its
      use in nutritional surveillance, particularly in populations at risk of
      malnutrition.

PMID- 1345449
TI  - Mortality experience in a rapidly developing economy in Taiwan: infant mortality,
      gender gap, and occupational risks.
AB  - Mortality data of Taiwan for 1981 through 1986 were analyzed using three
      different statistics in order to assess the role of environmental and lifestyle
      factors in causing mortality variations. Infant mortality rates from different
      geographic regions generally correlated well with overall mortality from all
      ages, suggesting that there are many common risk factors affecting the entire age
      range of the population. The mortality rates of tobacco- and alcohol-related
      causes of death and cancers were much higher in males than females. A number of
      cancer sites, including the lung, the liver, the stomach, and the nasopharynx,
      showed more than twofold excesses in males. In contrast, females had a tenfold
      excess of genital cancer and a 33% higher rate of diabetes. With rapid
      industrialization, occupational hazards played an increasing role in the
      development of cancer and other causes of death. During the study period,
      fishermen showed increased risk for cancers of the stomach, the esophagus, and
      the liver, while construction workers had an increased risk for cancer of the
      esophagus. Peasants and soldiers had an elevated suicide mortality. Among
      apprentices, fatal injuries were high. Findings from this study are useful in
      setting priorities for health and safety programs and directing efforts such as
      health education programs and other preventive strategies against disease.

PMID- 1345450
TI  - Child health and nutritional status in Ulaanbaatar, Mongolia: a preliminary
      assessment.
AB  - Over 85% of Mongolia's foreign trade and development aid, which formerly came
      from the USSR, have abruptly ceased causing shortfalls in almost all sectors. The
      UNICEF Mongolia Country Program and the East Asia and Pacific Regional Office
      (UNICEF/EAPRO) realized that Mongolian children are likely to suffer the most as
      reduced income and food availability aggravate problems associated with
      malnutrition. Hence, from 16 June-7 July 1992, a team from the Institute of
      Nutrition at Mahidol University, Thailand, collaborated with local UNICEF
      personnel and government health officials in designing and initiating the 1992
      Mongolian Child Nutrition Survey. This paper presents the preliminary survey data
      of 342 randomly selected children aged 0-48 months in Ulaanbaatar. Results
      indicate that the four major health and nutrition problems are protein energy
      malnutrition (PEM), iodine deficiency disorders, vitamin D deficiency, and an
      unusually high rate of acute respiratory infections. Also requiring more in-depth
      study are low birth weight, iron deficiency anemia and vitamin A deficiency.

PMID- 1345452
TI  - HIV-seroprevalence in the Northern Mariana Islands.

PMID- 1345451
TI  - Lessons learned from primary health care programs funded by the Aga Khan
      Foundation.

PMID- 1345453
TI  - The effect of atrial dilatation on reperfusion arrhythmias: development of
      supraventricular tachycardias on reperfusion with atrial stretching.
AB  - The study was aimed at investigating the effect of atrial dilatation on the
      genesis of supraventricular tachyarrhythmias following myocardial reperfusion.
      Experiments were carried out in 26 mongrel dogs under pentobarbital narcosis with
      artificial ventilation. Electrophysiological study was performed for studying the
      arrhythmic condition of the heart. Investigations were carried out: (i) in normal
      condition, (ii) during atrial stretching (balloon dilatation of the left atrium),
      (iii) in reperfusion following myocardial ischemia, (iv) in reperfusion combined
      with atrial stretching. On reperfusion the irritability of the atrium increased
      moderately (on atrial extrastimuli in 3 dogs non-sustained atrial tachycardia, in
      7 dogs repeated atrial responses could be induced). Reperfusion with atrial
      stretching, however, very markedly enhanced the atrial vulnerability, and in 19
      dogs atrial tachycardia appeared spontaneously. Comparison of the effect of
      atrial stretching to that of atrial stretching + reperfusion showed that the
      reperfusion significantly augmented the arrhythmia-inducing effect of atrial
      stretching. CLINICAL INVESTIGATIONS: Aortocoronary bypass operations were
      followed by development of supraventricular tachycardia in 41 out of 428 operated
      cases. Atrial dilatation was detected in 37 cases, mostly before the appearance
      of atrial tachycardia. The data seem to prove that atrial dilatation has an
      important part in the pathogenesis of supraventricular tachyarrhythmias following
      reperfusion of myocardial ischemia.

PMID- 1345454
TI  - Circadian pattern of serum androgens in women with Cushing's syndrome.
AB  - Circadian profiles of the serum levels of cortisol and five androgens were
      studied in 20 females including 8 controls, 7 patients with ACTH-dependent
      Cushing's syndrome and 5 with hypercortisolism due to adrenal adenoma. A
      significant 24-h periodicity was found for each steroid in all groups. Besides
      hypercortisolaemia, a significant increase of 11-hydroxyandrostenedione was shown
      in both forms of Cushing's syndrome. The most conspicuous finding was a decreased
      dehydroepiandrosterone and its sulphate in adrenal adenoma. The peaks for the
      studied steroids were shifted from the morning hours towards the noon in ACTH
      dependent Cushing's syndrome and towards the evening (for cortisol) and night
      hours (for androgens) in adrenal adenoma.

PMID- 1345456
TI  - Treatment of polyglandular autoimmune syndrome with cyclosporin-A.
AB  - The case history of a 30-year-old female patient is reported. Following an
      unknown viral infection that had occurred four years earlier, insulin-dependent
      diabetes mellitus vitiligo, Addison's disease, amenorrhoea, hyperthyreosis and,
      finally, severe pancytopenia with dominant thrombocytopenia developed. On the
      basis of clinical aspects and laboratory findings, an infrequent polyglandular
      autoimmune syndrome (type II) was verified. Substituent therapy and steroid stoss
      therapy also was introduced, without any sign of improvement. For the lack of
      therapeutic effect and owing to serious thrombocytopenic bleeding, treatment with
      Cyclosporin-A was indicated, which produced total remission of the illness.
      Nowadays the patient being on follow-up, has no sign of disease activity.

PMID- 1345455
TI  - Combined cyclosporin-A and methylprednisolone treatment of Graves'
      ophthalmopathy.
AB  - Twelve patients with Graves' ophthalmopathy (grade 1-6, ATA classification) were
      treated with Cyclosporin-A, systemically in combination with methylprednisolone.
      We observed slight or moderate favourable effect in 9 cases. Our data suggest
      that the benefit was due to the methylprednisolone, the effectivity of which was
      enhanced by the cyclosporin even in the glucocorticoid-resistant cases.

PMID- 1345457
TI  - The significance of birth weight discordance in twins.
AB  - The author found, among 329 twin pairs, 50 (15.2%) cases of weight discordancy
      reaching or exceeding 22%. Among the 50 twin pairs, there were 65 boys and 35
      girls, a sex ratio of 185.7. This degree of weight discordancy appears to be
      unrelated to maternal age, parity and gestational length. Growth retardation of
      one or both fetuses was significantly more frequent (80%) among weight-discordant
      than among concordant one (11.1%). There were more perinatal deaths between
      discordant than concordant twins. Among the twins who were born with evidence of
      growth discordancy, there was slightly increased incidence of abnormal
      presentation, delivery by cesarean section, and low Apgar score as compared to
      the concordants.

PMID- 1345458
TI  - Anticardiolipin antibodies: association with anti-DNA antibodies, disease
      activity, renal involvement and a history of thrombosis in systemic lupus
      erythematosus.
AB  - A one-year study was conducted to evaluate the clinical significance of
      anticardiolipin antibody (ACA) whether it was a reliable predictor for
      thromboembolic events and related diseases in systemic lupus erythematosus (SLE)
      patients. The correlation between ACA and anti-ds-DNA antibodies and disease
      activity was also studied. Of particular importance was the question if any
      association could be found between ACA positivity and renal disorders in SLE
      patients. One hundred and eighty-seven serum samples from 88 SLE patients were
      assayed for ACA. Clinical records of these patients were reviewed for a history
      of thromboembolic events, related diseases and renal disorders, 80.7% of the 88
      SLE patients were positive for ACA. The incidence of thrombosis and related
      diseases within this group was 35.1%. Since the correlation was not significant,
      it does not seem to be advisable to use elevated ACA values as predictive for
      thromboembolic events and related diseases. On the other hand, an apparent
      association between ACA levels, anti-DNA antibody levels and disease activity was
      found.

PMID- 1345459
TI  - Lipid abnormalities in uraemic patients on chronic haemodialysis.
AB  - Patients kept on haemodialysis because of chronic renal insufficiency were
      investigated for lipid profiles. The cholesterol level did not differ as compared
      to the age-matched control, while the triglyceride level was elevated. The
      correlation was found between the lipid parameters, period spent in dialysis
      programme and level of serum creatinine and urea. In renal failures of different
      origin the lipid levels are in relationship with the underlying disorders.

PMID- 1345460
TI  - Porphyrin studies in chronic renal failure and renal transplantation.
AB  - Haemoglobin (Hb), free erythrocyte porphyrins (FEPs), protoporphyrin and haem
      contents as well as delta-aminolevulinic acid (ALA)-dehydrase activity were
      estimated in blood samples from patients with chronic renal failure (CRF), from
      those with renal transplantation, and from healthy control subjects. In CRF
      patients a highly elevated FEPs level and a significantly increased
      protoporphyrin concentration were found. A well-defined decrease was observed in
      the mean value of ALA-dehydrase activity, Hb and haem contents when compared to
      the control values. However, in patients with renal transplantation significant
      decreases were observed in Hb and haem concentrations while the ALA-dehydrase
      activity and the FEPs and protoporphyrin concentrations were approximately at the
      control levels.

PMID- 1345461
TI  - Is the incidence of acute mountain sickness (AMS) at medium altitude in the
      Austrian Alps influenced by the height of home residence of the alpinist?
AB  - In previous studies the incidence of acute mountain sickness (AMS) at medium
      altitude was examined in the Austrian Alps, where many tourists come from low
      parts of Europe. This study assesses the influence of the height of home
      residence on the incidence of AMS at medium altitude. The severity of high
      altitude adaptation disorder was quantified by using a scoring system after an
      interview and a clinical examination in 84 lowlanders, mainly those from Hungary.
      Forty-two alpinists with a home residence of 800 to 1000 m served as control. The
      incidence of AMS was 1.4% at 2000 m and 7.4% in 3000 m. The most frequent
      symptoms were slight headache and peripheral or periorbital oedema. The AMS-score
      of the Hungarian alpinists did not differ significantly from that of the
      alpinists with a home residence of height 800 to 1000 m. CONCLUSION: in contrast
      to the situation at high altitude, at medium height tourists from lowlands are
      not at higher risk of AMS than other alpinists.

PMID- 1345462
TI  - Effect of choriocarcinoma supernatant on natural killer and lymphokine-activated
      killer cell activity.
AB  - The effect of JEG-3 choriocarcinoma supernatant on human natural killer cell and
      lymphokine-activated killer cell activity was investigated. Choriocarcinoma
      supernatants from JEG-3 cell lines were obtained at the time of their optimal
      growth. K562 erythroblastoid cells were used as target cells for natural killer
      and lymphokine-activated killer cell mediated lysis in a 51Cr release assay. The
      choriocarcinoma supernatants had a significant dose-dependent suppressive effect
      on natural killer and lymphokine-activated killer cell activity. This suppression
      was more expressed at high effector: target cell ratios. Therefore,
      choriocarcinoma supernatants appear to have potent inhibitory effects on many
      aspects of cellular immunity, although, additional studies should be performed to
      further characterize and identify immunoregulatory molecule(s) in choriocarcinoma
      supernatants.

PMID- 1345463
TI  - Can occupational guidelines for work-rest schedules be based on endurance time
      data?
AB  - Within the European Community, work is in progress to establish occupational
      guidelines for physical workload, including work-rest schedules. A model has been
      proposed which relies upon endurance time as a valid estimate of the short- and
      long-term physiological responses to continuous and intermittent exercise. On the
      basis of recent results from several Scandinavian research groups, the present
      paper questions the use of this model as a contribution to occupational
      guidelines. It is believed that the proposed model has a limited validity as a
      predictor of endurance time, as an indicator of short-term physiological
      responses, and as an estimator of risk for musculoskeletal disorders.

PMID- 1345465
TI  - Immunology of the cornea.

PMID- 1345464
TI  - [Treatment of Fournier's gangrene. A review based on 3 new cases].
AB  - We describe three new cases of Fournier's gangrene-a necrotizing fasciitis of
      urogenital or anorectal origin. Though in the initial report the disease was
      believed to be idiopathic, the source of infection or immuncompromising factors
      can be identified in nearly all cases today. We present a combination of
      aggressive surgical therapy and adjunctive use of Imipenem which was successful
      in the treatment of all our cases. By using fully resorbable nutrition colostomy
      could be avoided successfully.

PMID- 1345466
TI  - Anesthesia for the healthy child.
AB  - This article focuses on anesthesia for the healthy older infant and child, with
      nearly normal anatomy, physiology, and development, who is scheduled for an
      elective, relatively limited surgical procedure. Topics addressed in this section
      include: (1) monitoring technology used to enhance and maintain the
      anesthesiologist's clinical assessment; (2) pharmacological preparation designed
      to sedate, reduce anxiety, and/or make a child cooperative during the induction
      of anesthesia; (3) aspects of the induction of general anesthesia; (4) drugs
      commonly used for anesthetic premedication, induction, and/or maintenance; (5)
      aspects of emergence from anesthesia; and (6) equipment.

PMID- 1345467
TI  - Perioperative fluid and transfusion management.
AB  - Optimal perioperative fluid management in pediatric patients entails a knowledge
      of the effects of preoperative fasting, perioperative third space losses, and
      hemorrhage on the patient's fluid compartments. We explain which of the various
      available intravenous fluids should be used to correct various fluid and
      electrolyte losses that may occur. The authors also review techniques for
      limiting homologous transfusion requirements and discuss certain complications
      associated with blood transfusion.

PMID- 1345468
TI  - Anesthesia for the newborn and ex-preterm infant.
AB  - This article addresses the pertinent aspects of neonatal physiology and
      pharmacology, general considerations in the anesthetic care of surgical neonates,
      management details of selected neonatal surgical lesions, and anesthetic
      considerations for the ex-preterm infant.

PMID- 1345469
TI  - Preoperative evaluation and preparation of the pediatric patient.
AB  - A successful anesthetic is built on the foundation of the preoperative evaluation
      and preparation, six features of which will be discussed: (1) content and timing
      of the anesthesiologist's preoperative evaluation; (2) value of preoperative
      laboratory testing; (3) psychological effects of hospitalization and surgery; (4)
      approaches to psychological preparation; (5) pharmacological premedication
      (except for drugs designed to sedate or reduce anxiety, reviewed in the article
      by Bennie and McNiece); and (6) preoperative feeding schedules.

PMID- 1345470
TI  - Postanesthesia recovery.
AB  - The care provided in the postanesthesia recovery unit has become much more
      sophisticated in recent years. We address what type of care should be provided
      and what equipment is required to provide such care in the present day pediatric
      postanesthesia care unit. In this regard a wide variety of potential
      postanesthetic complications are described and their management is discussed. In
      addition, an update of pediatric cardiopulmonary resuscitation is presented
      including a discussion of surgery in the do-not-resuscitate patient.

PMID- 1345471
TI  - Pain management in children.
AB  - Recent research into the mechanisms of pain and pain management and the
      development of new pharmacological agents have greatly increased the
      possibilities for preventing and treating postoperative pain in the pediatric
      patient. This article briefly reviews the physiology of pain and the measurement
      and assessment of pain, and then discusses in some detail the various modalities
      useful in treating pain in the pediatric patient during the perioperative period.

PMID- 1345472
TI  - Noncardiac surgery in the patient with congenital heart disease.
AB  - The patient with congenital heart disease who presents for noncardiac surgery
      requires careful evaluation and planning to avoid adverse perioperative events.
      This chapter presents a physiological approach to the management of anesthesia
      for the most common congenital heart lesions. The various congenital heart
      defects are categorized into lesions resulting in: (1) left-to-right shunting;
      (2) right-to-left shunting; (3) complete mixing of pulmonary and systemic
      circulation; (4) complete separation of the pulmonary and systemic circulations;
      (5) increased myocardial work; and (6) mechanical obstruction of the airway.

PMID- 1345473
TI  - Anesthesia for selected procedures.
AB  - This article reviews selected procedures for which a particularly close working
      relationship between the surgeon and the anesthesiologist is essential for
      patient safety. Anesthetic considerations for upper and lower gastrointestinal
      endoscopies, bronchoscopy for aspirated foreign bodies, resection of mediastinal
      masses, thoracotomies for procedures requiring one-lung anesthesia, and surgery
      for burn patients are reviewed.

PMID- 1345474
TI  - Anesthesia outside the operating room.
AB  - Many new diagnostic and surgical procedures rely on immobile equipment such as
      computed tomography or magnetic resonance scanners, biplanar fluoroscopes, or
      radiotherapy units. To facilitate these procedures in infants and children,
      anesthesiologists must provide services in a variety of unique environments. This
      article reviews the anesthetic equipment and techniques that have been adapted to
      provide anesthesia for children outside the operating room.

PMID- 1345475
TI  - Malignant hyperthermia.
AB  - Malignant hyperthermia is a rare disease triggered by succinylcholine and the
      volatile anesthetic agents in genetically predisposed individuals. Recent studies
      have implicated an abnormality in the calcium release channel of the sarcoplasmic
      reticulum in skeletal muscle as the likely etiology. Genetic studies have
      narrowed the search for the chromosomal abnormality to human chromosome 19.
      Although the mortality from this disorder has dramatically decreased in the past
      decade due to the discovery of dantrolene, elective diagnosis of the disorder is
      only now appearing on the horizon.

PMID- 1345477
TI  - Biliary atresia.
AB  - Although biliary atresia is characterized by luminal obstruction of the
      extrahepatic bile ducts, the etiology and the pathophysiology of the liver are
      still controversial. The prognosis of biliary atresia has been improved after the
      introduction of Kasai's hepatic portoenterostomy, but there are still many
      problems to be solved in the treatment of this disease. Successful results of
      hepatic portoenterostomy depend on early diagnosis and operation, adequate
      operative technique, prevention of postoperative cholangitis, and precise
      postoperative management. However, we are on the verge of a new era in the
      therapy of biliary atresia combining portoenterostomy with liver transplantation.

PMID- 1345476
TI  - Pediatric liver cysts and abscesses.
AB  - Cystic liver lesions in children pose diagnostic and therapeutic dilemmas. When
      discovered during evaluation of abdominal distension, the likely cause is benign
      hepatic cyst. Surgical intervention aimed at resection is highly curative.
      Echinococcal disease, usually distinguishable from nonparasitic cystic disease,
      is rare in children in the United States. Therapy is aimed at sterilization and
      complete excision of hydatid tissue. Cystic liver lesions in septic children
      represent liver abscesses, pyogenic or amebic, which are frequently fatal if not
      diagnosed early and treated appropriately. Ultrasonography and computed
      tomography have simplified the diagnosis and treatment of these diseases, but a
      high index of suspicion is required because the signs and symptoms of liver
      abscess in children are nonspecific.

PMID- 1345478
TI  - Surgical jaundice in infants: other than biliary atresia.
AB  - After biliary atresia, the lesions responsible for surgical jaundice in the
      infant are perforation of the common bile duct, choledochal cyst, bile plug
      syndrome, and miscellaneous congenital lesions in descending order of frequency.
      Perforation of the common bile duct commonly presents with an insidious onset of
      bilious ascites and is best treated by simple peritoneal drainage. Choledochal
      cyst usually presents later in childhood but presents in infancy if obstruction
      of the biliary tree is complete or near complete. Excision is the treatment of
      choice. Any condition leading to alteration in bile composition may cause bile
      plug syndrome. Spontaneous resolution is the rule: occasionally, intraoperative
      irrigation is necessary. Most miscellaneous lesions lend themselves to operative
      correction.

PMID- 1345479
TI  - Choledochal cyst.
AB  - The most commonly encountered variant of choledochal cyst (type I) is
      characterized by fusiform dilatation of the bile duct. Patients usually come to
      medical attention within the first decade of life. The diagnosis is readily
      established by ultrasound or computed tomography. Choledochal cyst has been
      diagnosed in the fetus by maternal ultrasound. Treatment is by surgical excision.

PMID- 1345480
TI  - Portal hypertension.
AB  - Increased portal pressure is the product of both increased resistance to
      splanchnic flow through the liver and increased blood flow in the portal circuit.
      Although portal hypertension in children is less common than in adults, the
      important clinical end results are the same, ie, esophageal variceal hemorrhage,
      ascites, and hypersplenism. The etiology of portal hypertension in children is
      very different from adults in whom cirrhosis (most commonly secondary to alcohol)
      is the predominant cause. In children, extrahepatic obstruction due to portal
      vein thrombosis is the most common cause. However, as children survive longer
      with biliary atresia, cystic fibrosis, and other liver diseases, the incidence of
      intrahepatic obstruction causing portal hypertension is increasing. The treatment
      has also undergone a dramatic evolution over the last decade with the near
      extinction of portosystemic shunt procedures and their replacement with
      endoscopic treatment of esophageal varices and liver transplantation.

PMID- 1345481
TI  - Malignant liver tumors of children.
AB  - Malignant liver tumors in children are uncommon but have a high mortality.
      Survival rates have improved with advances in chemotherapy, imaging, tumor
      biology, and supportive care. However, complete surgical resection is the
      cornerstone of successful management. Important determinants of outcome are
      stage, histology, and resectability. A multidisciplinary team approach to the
      care of pediatric patients with liver tumors using the latest guidelines from
      clinical trials provides the best opportunity for care.

PMID- 1345482
TI  - Liver injuries in children: treatments tried, lessons learned.
AB  - Liver injuries continue to present the pediatric trauma surgeon with a formidable
      challenge. Most injuries are minor and are managed nonoperatively, but major
      injuries can be life-threatening and require immediate operation. Diagnosis is
      made clinically and confirmed by means by hepatic enzymes and computed
      tomography. The mortality associated with serious liver injuries in children is
      about 10%, usually from associated injuries, but exceeds 50% if major lacerations
      or juxtahepatic venous injuries are present.

PMID- 1345483
TI  - Liver transplantation in children.
AB  - Children with end-stage liver disease now have a greater chance of survival
      through treatment with hepatic transplantation. This article reviews the
      pediatric liver transplantation process, including selection and evaluation of
      candidates, operative procedures, postoperative complications, and long-term
      survival.

PMID- 1345484
TI  - Cholecystitis and cholelithiasis in children.
AB  - Cholecystitis and cholelithiasis are being recognized with increasing frequency
      in infancy and childhood. Hematologic disorders continue to account for a large
      proportion of cases; however, many children are noted with cholelithiasis in
      association with total parenteral nutrition, ileal disorders, and prolonged
      fasting. Spontaneous stone resolution has been noted in many cases in infancy and
      a period of observation is indicated in the absence of obstructive symptoms.
      Cholecystectomy remains the procedure of choice for symptomatic cholelithiasis
      and cholecystitis and a laparoscopic procedure is possible in most cases after
      infancy.

PMID- 1345486
TI  - Peripheral and central venous access.
AB  - Peripheral venous access is indicated for the administration of fluids, drugs, or
      if nutrients when other routes are unavailable. Central venous access is
      indicated if peripheral access is unsuccessful or if hypertonic, irritant, or
      vasoconstrictor solutions are used. Because of anatomical variations, different
      peripheral cannulation sites are more appropriate in different age groups. The
      preferred sites for long-term central venous access in infants and children are
      the external jugular, facial, internal jugular, saphenous veins at the groin, and
      subclavian veins. The practical aspects of peripheral and central venous access
      and the complications are discussed.

PMID- 1345485
TI  - Arterial access in infants and children.
AB  - Intraarterial access is used to provide continuous monitoring of systemic
      arterial blood pressure and to provide access to sample arterial blood. The use
      of chronic indwelling arterial catheters became commonplace in the 1970s and was
      rapidly adapted to the care of infants and children. The placement of
      intraarterial catheters can be technically challenging for even the most
      experienced surgeon, especially in small infants. Arterial catheters can directly
      injure vessels, resulting in thrombosis or occlusion. Distal embolization or
      ischemia can also occur. Catheter flushing may cause retrograde flow with the
      potential for embolization at remote sites. Local insertion site complications,
      such as hematoma, hemorrhage, and infection, can occur. Arterial catheters can
      also be a source of systemic sepsis. Although the risks and complication rates
      are low, the potential for devastating injury exists and deserves the greatest
      respect whenever placement of an arterial catheter is contemplated.

PMID- 1345487
TI  - Permanent central venous access devices.
AB  - The development of permanent central venous access devices in the last 20 years
      has been accompanied by decreased complication rates, improved patient comfort,
      and increased cost-effectiveness. Subclavian venous access, first applied to
      infants and small children in the early 1970s, has given way to the Silastic
      permanent right atrial catheter by both cutdown and percutaneous techniques. The
      disadvantages of an occlusive aseptic dressing, frequent catheter irrigation, and
      disturbance of body image led to development of the totally implantable venous
      access system, which has been successfully used for long-term infusion of
      chemotherapeutic agents, antibiotics, blood products, and total parenteral
      nutrition. The recent introduction of permanent peripheral central venous
      catheters has further decreased the expense and complication rate of long-term
      venous access in infants and children. These developments and the accumulated
      expertise in finding alternative venous access sites (common facial, deep
      inferior epigastric, lumbar, and azygos veins) have helped minimize mechanical
      and septic complications and have increased the safety of even the most difficult
      venous access procedures.

PMID- 1345488
TI  - Intraosseous infusion in infants and children.
AB  - Intraosseous infusion was used extensively for the parenteral administration of
      blood, fluids, and pharmacological agents in the 1940s. The technique was
      "discovered" and popularized again during the 1980s. Substances injected
      intraosseously are found rapidly in the central circulation. Drugs should be
      given in the equivalent dose used for intravenous administration. The preferred
      site for intraosseous infusion is the proximal tibia. Insertion is performed 1 to
      3 cm below the tibial tuberosity on the flat anteromedial surface of the tibia.
      After about 5 years of age, the distal tibia or femur are the preferred sites.
      Needles made specifically for resuscitative intraosseous infusion are available.
      Increased awareness of the role of intraosseous infusion, familiarity with the
      technique of insertion, and careful use of landmarks to guide insertion should
      minimize complications.

PMID- 1345489
TI  - Fluids and electrolytes in infants and children.
AB  - The fluid and electrolyte management of the surgical neonate must take into
      account the acute transition to extrauterine life superimposed on the gradual
      changes associated with fetal and neonatal maturation and growth. With this
      transition, there are acute changes in body water distribution, and a striking
      increase in evaporative losses from the skin and respiratory tract. These
      changes, as well as those in renal function and sodium balance in the preterm and
      full-term infant are discussed.

PMID- 1345490
TI  - Intravenous nutrition for the pediatric patient.
AB  - Nutritional management of infants and children differs from that of adults
      because of the extra requirements for growth and the limitations of physiological
      immaturity. Although parenteral nutrition (PN) is an accepted practice and a
      potentially life-saving therapy for pediatric patients who cannot be fed through
      their gastrointestinal tract, it is associated with the risk of serious
      metabolic, mechanical, and infectious complications. Candidates for PN should be
      selected according to well-defined indications, with initial nutritional
      assessment and with careful attention given to fluid, electrolyte, vitamin, trace
      element, and caloric requirements. Total calories should be administered so that
      the nonprotein-calorie to gram-nitrogen ratio is in the range of 150 to 250:1.
      Although short-term supplemental nutritional support can be administered through
      a peripheral vein, long-term total PN is best delivered by central venous access.
      PN should be initiated and monitored in accordance with well-established
      protocols. The lowest complication rate and highest cost-effectiveness are
      achieved by an interdisciplinary team that includes one or more nurses,
      dietitians, pharmacists, and physicians. The development of safe, reliable, and
      miniaturized intravenous pumps with built-in monitors has made home parenteral
      nutrition possible and desirable in selected patients.

PMID- 1345491
TI  - Blood products.
AB  - Modern transfusion therapy offers the seriously ill patient an array of blood
      products, designed to improve oxygen delivery, maintain intravascular volume,
      suppress infection, and induce hemostasis. Depending on the patient's clinical
      circumstance, the choice of product may need to incorporate consideration of the
      state of intravascular volume, history of prior transfusion reactions, the
      possible existence of serum antibodies directed against the relevant blood
      component, and the risk of transmission of infectious disease, as well as the
      relative cost of the blood product chosen. Fortunately, the contemporary blood
      bank has acquired considerable expertise in preparing safe products and in
      providing sound guidance for the clinician in their proper use.

PMID- 1345492
TI  - Isotope studies in children: an update.
AB  - Hepatobiliary scintigraphy is an accurate, simple, and relatively noninvasive
      method for the diagnosis of biliary atresia, a condition in which early diagnosis
      is of paramount importance. Radionuclide gastrointestinal transit studies are
      useful in devising the surgical approach in children with suspected
      gastroesophageal reflux. Renal scintigraphy in the newborn period is used to
      decide the need for surgical intervention in a hydronephrotic kidney. Relatively
      new radiopharmaceuticals such as metaiodobenzyleguanidine, thallium, and
      deoxyglucose are useful in detecting tumors and in predicting the viability.

PMID- 1345493
TI  - Computed tomography imaging of abdominal trauma in children.
AB  - The authors discuss the role of computed tomography (CT) in the evaluation of
      children following blunt abdominal trauma. Appropriate techniques for scanning
      children are described, as well as clinical indications that place children at
      high risk and low risk for abdominal injury. Examples of both solid organ and
      bowel injuries are shown, with special emphasis on the correlation of CT
      appearance and clinical outcomes. The authors conclude that CT is an effective
      tool for the diagnosis of abdominal injury in the pediatric patient, and that the
      clinical impact of CT appears to be changing with the increasing use of
      nonoperative therapy for solid organ injury.

PMID- 1345494
TI  - Selected topics in hepatobiliary imaging.
AB  - With the advent of ultrasound, computed tomography, and magnetic resonance
      imaging, hepatobiliary imaging is changing. The advantages and disadvantages of
      each new imaging modality will be reviewed. The radiographic approach of a child
      who presents with a mass or jaundice will be discussed. The role of duplex
      Doppler ultrasound in the preoperative and postoperative management of liver
      transplantation patients will be presented.

PMID- 1345495
TI  - Imaging of abdominal masses in children.
AB  - Abdominal imaging has undergone extensive change over the past several years. In
      many cases, the developments have been so rapid as to preclude an orderly
      comparison of competing procedures with prospective comparison studies.
      Consequently, no rigid imaging protocol will be universally accepted and many
      issues are unresolved. This article reviews the various imaging procedures used
      in imaging pediatric abdominal masses with emphasis on technique, indications,
      risks, and costs. The relative merits of imaging modalities in various clinical
      situations are outlined and specific recommendations are given.

PMID- 1345496
TI  - New concepts in imaging of the gastrointestinal tract in children.
AB  - This article highlights some of the significant recent advances in imaging of the
      pediatric gastrointestinal tract that have occurred over the last decade. The
      current roles of the newer imaging modalities, including ultrasound, computed
      tomography, and magnetic resonance imaging, are discussed and illustrated.
      Particular emphasis is given to antenatal evaluation, suspected gastric outlet
      obstruction, inflammation, and other causes of the acute abdomen. Enhancements in
      fluoroscopic techniques are outlined, including the use of the newer contrast
      agents as well as air reduction of intussusception. Continued good communication
      between the pediatric radiologist and pediatric surgeon is vital to improve the
      care to children with disorders of the gastrointestinal tract.

PMID- 1345497
TI  - Contrast studies of the gastrointestinal tract in the neonate.
AB  - The approach to imaging the gastrointestinal tract in neonates, including both
      the method of examination and the choice of contrast media, is specialized and
      requires close cooperation between the pediatric surgeon and the pediatric
      radiologist experienced in the evaluation and care of these children. Although
      the physical examination and the plain radiographic findings are occasionally
      sufficient to make a specific diagnosis, contrast studies are also frequently
      required. The use of the plain radiographs in planning the approach to further
      imaging and the selection of the appropriate contrast media for a variety of
      common situations are discussed.

PMID- 1345498
TI  - Interventional procedures in pediatrics.
AB  - Pediatric intervention has grown substantially over the last 20 years.
      Interventionalists now work closely with surgeons and other physician groups to
      diagnose and treat a wide variety of pediatric disease processes. Using image
      guidance and intravenous sedation in most instances, the interventionalist
      performs vascular and nonvascular procedures such as embolotherapy, abscess
      drainage, dilation of strictures, biopsy, and percutaneous nutritional
      procedures, to name a few. It is my hope that the current and future techniques
      will lead to improved, more effective, and safer methods for treating sick
      children of all ages.

PMID- 1345499
TI  - A biologic approach to tumor imaging.
AB  - The planning of imaging protocols for follow-up evaluation of children with
      cancer should be based on knowledge of biologic behavior of the tumor rather than
      on intuitive protocols. This article gives examples of how such biologic
      information can be integrated into imaging protocols.

PMID- 1345500
TI  - Practice assessment and quality of care.

PMID- 1345501
TI  - Bilingualism: theoretical perspectives of language diversity.
AB  - Bilingualism and second language acquisition are discussed with reference to
      different theoretical perspectives. An integrated definition of bilingualism is
      provided and concepts underlying second language acquisition are presented.
      Theoretical perspectives according to Dodson (1985), Skinner (1985) and Krashen
      (1982) are explored. It is concluded that due to the diverse nature of
      bilingualism, a single universal theory of second language acquisition does not
      seem feasible. The need for an increased awareness of the complexity of
      bilingualism and second language acquisition, particularly within the
      multicultural and multilingual South African context, is highlighted.

PMID- 1345502
TI  - Language abilities of 18-month-old Zulu speakers.
AB  - The receptive, expressive and pragmatic language abilities of 18-month-old Zulu
      speakers were assessed in order to obtain preliminary norms. Twenty-five
      participants of the Birth to Ten cohort study were investigated using parent
      reports, mother-child and tester-child interactions. Data was transcribed and
      analysed using nonparametric statistics. Results demonstrated that receptively
      subjects understood two-part instructions. Expressively, the mean lexicon was
      4.12 words and mean length of utterance 0.65. Pragmatically, subjects were
      functioning on a nonverbal level and exhibited culture-specific items. The
      results provided information which could enable speech, language and hearing
      therapists to engage in primary and secondary prevention. An appropriate test
      battery for these children is discussed.

PMID- 1345503
TI  - Future trends in language intervention: addressing cultural bias in service
      delivery.
AB  - In this paper the cultural biases in a widely-used language intervention approach
      -the Hanen Early Language Parent Program--that trains parents to be
      conversational partners with their language-delayed children, are explored. In
      many respects this program represents the best of current clinical practice. It
      is empirically and theoretically grounded in recent research on parent-child
      interaction; studies have documented its efficacy; and it is a family-centred
      approach. And yet, in clinical practice, it does not work with all families. Not
      surprisingly, these families are often from nonmainstream backgrounds. Potential
      reasons for the lack of effectiveness with some families become apparent as
      research on patterns of language socialization in a wide variety of cultures is
      reviewed. This review reveals that all of the basic premises of this program rest
      on culturally relative beliefs and values. Specifically considered are cultural
      variation in (1) aspects of social organization related to interaction, (2) the
      value of talk, (3) how status is handled in interaction, (4) beliefs about
      intentionality, and (5) beliefs about teaching language to children. Suggestions
      for incorporating this information into clinical services with nonmainstream
      families are offered.

PMID- 1345504
TI  - Augmentative and alternative communication in South Africa: accessibility and
      implementation.
AB  - This paper deals with the development of a community-based service for the
      implementation of augmentative and alternative communication (AAC) strategies for
      people with severely limited verbal expression. The concept of community-based
      intervention is explained and the process of training as done in the Centre for
      Augmentative and Alternative Communication (CAAC) is described. Data of pre- and
      post-training evaluations is discussed as well as follow-up data obtained in the
      various training contexts. Finally, critical issues related to the follow-up data
      are discussed.

PMID- 1345506
TI  - The provision of speech, language and hearing services in a rural district of
      South Africa.
AB  - In this paper the delivery of a speech, language and hearing therapy (SLHT)
      service in a rural area is discussed. In the light of the need to relate the
      delivery of this service to principles of primary health care (PHC) and community
      based rehabilitation (CBR), a brief theoretical background is given. Obstacles to
      service delivery are then presented, followed by a description of some attempts
      to implement principles of PHC and CBR. The author concludes that many challenges
      need to be faced in providing SLHT services that will benefit the majority of the
      population of South Africa.

PMID- 1345505
TI  - [Guidance to parent of black babies with a cleft lip and palate].
AB  - There are indications that the parents of babies with a cleft lip and palate
      often require more information regarding their baby's birth defect than what is
      given to them. In South Africa shortcomings exist in the literature covering the
      specific requirements of parents of black cleft lip and palate babies. In this
      study the unique requirements of parents of black cleft lip and palate babies was
      determined and, based on these results, an information pamphlet was prepared for
      this population group. Based on the results obtained with the help of fifteen
      participants it was established, firstly, that the needs of black South-African
      parents of children with a cleft lip and palate are similar to the needs of
      parents of babies with the same birth defect world-wide. Secondly, it was
      established that the information pamphlet which was compiled as part of the study
      made a positive contribution to parent guidance conducted with the participants.
      Important therapeutic implications were also reflected by the results.

PMID- 1345507
TI  - The nature and management of communication disorders in a rural area: the role of
      the community speech and hearing therapy workers.
AB  - Six hospitals where Community Speech and Hearing Therapy Workers (CWs) are
      working in Gazankula were visited. Firstly, data were collected from records,
      reports and case files over an 18 month period to determine the nature and
      prevalence of the communication disorders seen by the CWs. Secondly, the CWs were
      interviewed about their work situation, organisation of their time and
      intervention strategies used with communicatively disordered people in order to
      evaluate the efficacy of their work. Methodological issues requiring
      consideration when undertaking this type of research are discussed. The results
      are discussed in terms of the implications for course modifications as well as
      policy decisions within the profession of Speech and Hearing Therapy.

PMID- 1345508
TI  - Community work project in Gazankulu: a community-based training experience.
AB  - Speech Pathology and Audiology students at the University of the Witwatersrand
      participated in a field trip to learn about rural community work. In
      collaboration with rehabilitation workers at Tintswalo Hospital, Gazankulu,
      projects in pre-school language stimulation, aphasia assessment and intervention,
      and hearing screening were undertaken. Projects adhered to community work
      principles. These were successful in terms of both providing a service to the
      community and teaching students principles and practice of community work.

PMID- 1345509
TI  - The Renfrew Word Finding Scale: application to the South African context.
AB  - The Renfrew Word Finding Scale (Renfrew, 1988) was administered to 30 Indian
      (Group A) and 30 White (Group B) Durban English speaking children aged between
      eight and nine years to determine its suitability for assessment of expressive
      vocabulary. Mean scores for both groups were statistically compared to the
      British norms in terms of mean raw scores and mean mental age. Mean scores for
      groups A and B were compared to each other. Item analyses were carried out to
      obtain further information regarding possible lexical characteristics for each
      group and common problems with certain items. Both groups performed significantly
      poorer than expected according to the British norms. Group A was significantly
      lower than Group B, thus indicating the test's unsuitability for use with these
      population groups in its present form.

PMID- 1345510
TI  - Euthanasia.

PMID- 1345511
TI  - Euthanasia.

PMID- 1345512
TI  - Ectrodactyly-mandibulo-facial dysostosis: case report and delineation of an
      entity.
AB  - We describe a 24-year-old woman with tetramelic ectrodactyly, mandibulo-facial
      dysostosis and cleft uvula. This rare association has previously been reported in
      two families, but with ectrodactyly affecting only the feet. We propose the new
      term ectrodactyly-mandibulo-facial dysostosis for this entity.

PMID- 1345513
TI  - Microcephaly, focal segmental glomerulonephritis and marfanoid habitus in two
      sibs.
AB  - Two female sibs aged 15 and 18 years with microcephaly, mental retardation and
      marfanoid habitus who developed focal segmental glomerulonephritis leading to
      renal failure are described. This combination of features appears to represent a
      unique syndrome distinct from previous reports of microcephaly in association
      with the nephrotic syndrome. The mode of inheritance is likely to be autosomal
      recessive.

PMID- 1345514
TI  - Thanatophoric dysplasia of the straight-bone type (type 2).
AB  - We describe two cases of type 2 thanatophoric dysplasia. Cloverleaf skull and
      relatively straight, shortened long bones distinguish this condition from the
      more common type 1 thanatophoric dysplasia.

PMID- 1345515
TI  - Hypoplastic thumbs and hydranencephaly: a new syndrome?
AB  - We report a fetus with hypoplastic thumbs and hydranencephaly. The features did
      not fit well into any syndrome described in the London dysmorphology database,
      and we suspect this may represent a previously undescribed syndrome, although a
      diagnosis of XK-aprosencephaly syndrome remains possible.

PMID- 1345516
TI  - Alopecia, mental retardation, epilepsy and microcephaly in two cousins.
AB  - We report two cousins, born to consanguineous parents, with an alopecia-mental
      retardation syndrome and the additional features of microcephaly and epilepsy.
      Similar reported cases are reviewed and genetic heterogeneity is suggested.

PMID- 1345517
TI  - Skin mastocytosis, hearing loss and mental retardation.
AB  - A girl with skin mastocytosis, hearing loss, microcephaly, mild dysmorphic
      features and severe mental retardation is described. The symptoms of the child
      resemble those reported in 1990 by Wolach et al. in another patient sufficiently
      to suspect the same entity in both. Inheritance may be autosomal recessive.

PMID- 1345519
TI  - Scalp lipomas and cerebral malformations--report of a case and review of the
      literature.
AB  - A child is reported with a scalp lipoma and underlying bony skull defect and
      porencephaly. The clinical picture is compatible with a diagnosis of
      encephalocraniocutaneous lipomatosis, although there is no alopecia overlying the
      lipoma and no scleral lesions. In addition, this child has unilateral ptosis and
      syndactyly. This report extends our appreciation of the phenotype of this
      neurocutaneous disorder.

PMID- 1345520
TI  - [Endothelin--new mediator or hormone?].

PMID- 1345518
TI  - Association of autosomal dominant cleft lip and palate and translocation
      6p23;9q22.3.
AB  - Orofacial clefting (OFC) is genetically complex in that no single gene defect is
      responsible for all forms. We have identified a family who exhibit autosomal
      dominant orofacial clefting together with some features of ectodermal dysplasia.
      In this family there is concordance between these features and an apparently
      balanced translocation t(6;9)(p23;q22.3) which raises the possibility that a
      locus for one form of orofacial clefting may be located at one of the
      translocation breakpoints. Fluorescent in situ hybridization has shown that a
      candidate gene for OFC, which maps to distal 6p, is located on the derived
      chromosome 9 in affected individuals from this family. Further characterization
      of the translocation breakpoints and of their relationship with the candidate
      gene will determine whether a gene important for normal facial and/or ectodermal
      development is disrupted in this family.

PMID- 1345521
TI  - Uptake of thyroxine by cultured human adipocyte precursors isolated from lean and
      obese subjects.
AB  - The mechanism of thyroxine uptake by human adipocyte precursors has been studied
      in primary culture. Also the rates of transport of this hormone into the isolated
      cells of adipose tissue were compared for lean and obese subjects. It was
      demonstrated that thyroxine transport into the human adipocyte precursor cells is
      an active, energy-dependent process characterized by very low rate (Km = 10
      pmol/l, Vmax = 8 fmol FT4/10(6) cells/min.). By comparing the rates of thyroxine
      transport into the precursor cells of adipocytes isolated from adipose tissue of
      lean and obese subjects it was possible to demonstrate a clear tendency to the
      lowered rate of transport of thyroxine to the cells in obesity. The results of
      this study suggest that the lowered rate of thyroxine transport to preadipocytes
      and adipocytes observed in obesity may significantly influence the metabolic
      state of these cells.

PMID- 1345522
TI  - [Activity of Ca(+2)Mg(+2) --ATPase in erythrocyte membranes of women with
      diabetes mellitus type I].
AB  - The activity of Ca(++)-Mg++ ATP-ase present in erythrocyte membranes was
      determined in basal conditions and following stimulation with calmodulin in 8
      women with insulin-dependent diabetes and in 9 healthy women. The isolation of
      erythrocyte membranes and the determination of activity of Ca(++)-Mg(++)-ATP-ase
      were carried out according to the method of Gietzen et al. A decrease in the
      activity of Ca(++)-Mg(++)-ATP-ase in basal conditions was found in fractions with
      the highest erythrocyte content obtained from diabetic patients. After
      stimulation with calmodulin the activity of Ca(++)-Mg(++)-ATP-ase in all the
      fractions was lower in diabetic patients than in the controls. Low activities of
      the enzyme were accompanied by high values of HbA1c. The results suggest that
      glycosylation of the ATP-ase or/and calmodulin may be the main cause of the
      observed fall in the enzyme activity in diabetes. Also the disturbances
      concerning the cumulation of intracellular calcium may be related to the changes
      caused by glycosylation of Ca(++)-Mg(++)-ATP-ase or/and calmodulin.

PMID- 1345523
TI  - [Investigation of the insulin gene by the amplification method in vitro].
AB  - Forty one patients with familial non-insulin-dependent diabetes (type 2) were
      included into the study. The fragment of insulin gene including the sequences
      coding for beta chain and part of C-peptide as well as 5'untranslated region was
      amplified in vitro by using the polymerase chain reaction. The digestion of the
      fragments by using the restriction enzyme Pst I followed by electrophoretic
      separation allowed to recognize the alpha and beta alleles of insulin gene. The
      investigations have shown that the beta allele occurs more frequently in diabetic
      patients than in healthy control subjects (P < 0.05).

PMID- 1345525
TI  - [Effect of calcitonin on secretion of TSH stimulated by giving thyroliberin (TRH)
      in euthyroid subjects].
AB  - The effect of calcitonin on TRH-induced secretion of thyrotropin was studied in
      15 subjects with normal thyroid function. It was found that calcitonin has no
      significant effect on thyrotropin secretion both in basal conditions and
      following stimulation with TRH.

PMID- 1345524
TI  - [Thyroid function in patients during long-term treatment with amiodarone].
AB  - Thyroid function was evaluated in 31 patients with disturbances of heart rhythm
      both before and after 13 months of treatment with amiodarone. An increase in
      blood serum T4 concentration and transient increase (only during the first three
      months of treatment) in TSH concentration have been observed in almost all the
      patients studied. Clinically evident form of hyperthyroidism was found only in
      one female patient. In two patients the changes in hormone concentrations
      suggesting hyperthyroidism were not accompanied by clinical manifestations, and
      in four patients there was no clinical hypothyroidism despite hormone levels
      suggesting such a state. In addition to the determinations of T3, T4 and TSH also
      the results of TRH-TSH test played an important role in diagnosing both hypo- and
      hyperthyroidism.

PMID- 1345526
TI  - [Effect of thermal dehydration on blood levels of hormones regulating volume and
      electrolyte content of sweat in patients with kidney transplantation].
AB  - The thermal dehydration test was performed in 12 patients with renal transplant
      and in 20 healthy subjects. The study was aimed at the evaluation of the effect
      of volume regulating hormones on electrolyte composition of thermal sweat in
      patients with renal transplant. Blood plasma renin activity (PRA) as well as
      plasma concentrations of aldosterone (ALD), vasopressin (AVP) and atrial
      natriuretic peptide (ANP) were determined before and after thermal dehydration in
      all the subjects studied. In all the subjects sweat was also collected after 15
      and 45 minutes of exposition to heat and the concentrations of sodium, potassium
      and chloride were determined in all sweat samples. Significantly elevated PRA and
      ANP concentrations and significantly lowered plasma AVP concentrations but normal
      ALD levels were found before thermal dehydration test in all the patients with
      renal transplant. After the exposition to heat lasting 1 hour the direction of
      changes was similar, their magnitude was, however, different in renal transplant
      patients than in healthy subjects. In addition, lower concentrations of sodium
      and chloride in thermal sweat and lower total concentration of sweat solids were
      found in renal transplant patients than in healthy controls. No significant
      correlation was found between the plasma concentrations of the hormones
      determined and the electrolyte concentrations of thermal sweat both in the renal
      transplant patients and in healthy subjects. The results suggest that the volume
      regulating hormones have no effect on the electrolyte composition of thermal
      sweat induced by short exposition to heat both in renal transplant patients and
      in healthy subjects.

PMID- 1345527
TI  - Plasma endothelin 1/2 levels in healthy blood donors as measured by RIA--a
      clinical application.
AB  - Normal endothelin 1/2 levels and their correlation with age were evaluated. For
      clinical application of the endothelin 1/2 RIA test, optimum storage conditions
      were investigated. Plasma endothelin 1/2 (ET) levels were measured in 36 healthy
      blood donors, mostly males, of mean age 36 +/- 8 years, subdivided into three age
      groups: 17-30, 31-40 and above 40 years old. The mean normal ET levels in the
      three age groups, and corresponding standard deviations, were: 0.58 +/- 0.19,
      0.62 +/- 0.31, and 0.80 +/- 0.28 fmol/ml, respectively. The mean ET level for the
      whole normal population was 0.66 +/- 0.28 fmol/ml. Only differences between mean
      ET levels for the first and last groups were statistically significant (p <
      0.05). Differences between mean ET levels in smokers (53% of total population)
      and non-smokers, women and men, irrespective of age, were found not to be
      statistically significant. At this stage of our work, we conclude that other
      factors than age alone play a role in enhancing ET levels above the age of 41
      years. In our study of optimum storage conditions for endothelin 1/2, we found
      that after one week of storage at -24 degrees C the mean level of ET measured in
      frozen plasma dropped to 85% of the initial activity, while after the same period
      the respective decrease in ET activity in frozen extracts was 49%. Over the next
      two weeks, ET levels in plasma and extracts dropped to 57% and 32% of "zero time"
      activities, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345528
TI  - Chronic metoclopramide treatment stimulates T lymphocyte proliferation in the
      spleen but not in the thymus.
AB  - The effect of chronic metoclopramide administration (for 10 days at a daily dose
      of 5 mg/kg body weight subcutaneously) on cell proliferation in spleen and in
      thymus was investigated. Cell proliferation was evaluated by the stathmokinetic
      method with the use of vincristine. It was found that metoclopramide
      administration results in a statistically significant increase in the value of
      the mean mitotic activity rate index (MMAR) of splenocytes in the areas around
      arteries. At the same time no statistically significant changes were demonstrated
      in the MMAR index values obtained for splenocytes present in the germinal centers
      of the spleen. No significant changes in the MMAR index could also be found for
      thymocytes.

PMID- 1345529
TI  - [Isolation of prolactin from lyophilized porcine pituitary glands].
AB  - The optimal conditions for lyophilization of porcine pituitary glands and
      isolation of pure prolactin from lyophilized preparation have been investigated.
      The isolation method consisted in the extraction of crude pituitary preparation
      with acidified acetone followed by precipitation of crude prolactin preparation
      (acid acetone powder) by increasing the concentration of acetone in the extract
      to 92%. Further purification of prolactin was achieved by fractional
      precipitation at varying pH values and gel filtration on Sephadex G-75 column in
      a pH 7.5 phosphate buffer. This final procedure resulted in obtaining the
      monomeric form of prolactin. The identity of the isolated hormone was confirmed
      by spectrophotometric and radioimmunological methods as well as by polyacrylamide
      gel electrophoresis.

PMID- 1345530
TI  - [Involvement of the pineal gland in regulation of neoplasm growth].

PMID- 1345531
TI  - [Hyperglycemia--a common mechanism for chronic complications in diabetes?].

PMID- 1345532
TI  - [Lipid metabolism in children and adolescents with insulin dependent diabetes.
      II. Evaluation of changes in lipoprotein A-I in children and adolescents with
      insulin dependent diabetes].
AB  - The levels of lipoprotein A-I (LP A-I) containing apolipoprotein A-I (apo A-I)
      and devoid of apolipoprotein A-II (apo A-II) have been determined in a group of
      86 children and adolescents with insulin-dependent diabetes of age between 1.3
      and 22 years. The duration of diabetes in the studied group ranged between 0.25
      and 15 years. The patients studied were further divided into subgroups taking
      into account the duration of diabetes as well as the occurrence of complications
      of diabetes, obesity and predisposition to early development of atherosclerosis
      in family history. The analysis of the results took into account the relations
      between the levels of LP A-I and other parameters of lipid metabolism like
      cholesterol, triglycerides, HDL-cholesterol, apo A-I and apo A-II concentrations
      as well as the effectiveness of metabolic control of diabetes. LP A-I
      concentration was the lowest in group of children with diabetes lasting up to one
      year. This parameter was correlated positively with the levels of HDL-cholesterol
      and apo A-I, and negatively with HbA1c. It was not related to the coexisting
      complications, obesity or predisposition to atherosclerosis in family history.
      The above results indicate that the state of metabolic control of diabetes
      significantly influences the level of LP A-I. Considering the importance of LP A
      I in preventing atherosclerosis it should be stressed that a decrease in its
      level during the period of prolonged hypoglycemia constitutes still another risk
      factor for development of atherosclerosis in diabetic children and adolescents.

PMID- 1345533
TI  - [Lipid metabolism in patients with insulin dependent diabetes. III. Effect of
      metabolic control of diabetes on the concentration of some blood serum lipid
      constituents in patients with insulin dependent diabetes].
AB  - The levels of the following blood serum lipid constituents: total cholesterol,
      triglycerides, phospholipids, HDL-cholesterol, lipoprotein fractions, as well as
      apolipoproteins AI, AII and B, have been determined in patients with insulin
      dependent diabetes lasting from 3 months to 15 years in relation to the degree of
      metabolic control characterized by the levels of fructosamine and glycosylated
      hemoglobin HbA1c. The group of patients having the level of HbA1c exceeding 10%
      was characterized by significantly higher levels of cholesterol, triglycerides
      and Apo-B, and lower content of alpha-lipoprotein as compared to the group with
      HbA1c level beneath 10%. When fructosamine concentration was considered as an
      index of metabolic control of diabetes, it was found that the levels of
      cholesterol, phospholipids and apolipoproteins apo-A and apo-AI are highest in
      the group with the poor metabolic control and differ significantly from the
      respective values found in patients with mediocre and good metabolic control.
      Considering biological role of the individual lipids and lipoproteins, it should
      be stressed that the proper control of glycaemia is important for preventing the
      development of atherosclerosis in patients with insulin-dependent diabetes.

PMID- 1345534
TI  - [Lipid metabolism in patients with insulin dependent diabetes. IV. Effect of sex,
      age, excess body weight, duration of diabetes, insulin dosage and family history
      on lipid metabolism in patients with insulin dependent diabetes].
AB  - The levels of the following blood serum lipid constituents: total cholesterol,
      triglycerides, phospholipids, HDL-cholesterol, apolipoproteins AI, AII and B, and
      lipoprotein fractions have been determined in patients with insulin-dependent
      diabetes in relation to sex, age, duration of diabetes, coexistence of obesity,
      insulin dosage and history of genetic predispositions. The age of the patients
      was between 1.3 and 22 years and the duration of the disease ranged between 3
      months and 15 years. The analysis of the results revealed that sex, age, daily
      insulin dose and the known genetic predispositions have no influence on the
      values of the parameters of lipid metabolism. However, an increase in the levels
      of cholesterol, HDL-cholesterol, triglycerides and apolipoproteins AI and B was
      observed along with the progressing duration of the disease. An increase in the
      levels of cholesterol, apolipoprotein B and beta-lipoprotein, and a decrease in
      the level of alpha-lipoprotein have been found in diabetic children with
      coexisting obesity. The above analysis indicates that besides metabolic control
      of diabetes its duration and accompanying obesity may negatively influence the
      course of the disease contributing to the precocious development of
      atherosclerosis.

PMID- 1345535
TI  - Prolactin and LH release in response to vasoactive intestinal peptide (VIP)
      administration in spontaneously hypertensive and normotensive rats.
AB  - Vasoactive intestinal peptide (VIP) was injected intravenously at a dose of 10
      micrograms in spontaneously hypertensive and normotensive Wistar-Kyoto rats. In
      order to evaluate the hemodynamic and hormonal effects of this peptide, the mean
      arterial pressure, heart rate as well as a serum rLH and rPRL levels, the
      contents of LH-RH in hypothalamus and the content of LH in pituitary tissue were
      determined. The same procedure was applied in rats receiving placebo. Serum rPRL
      concentration was measured additionally after combined administration of
      VIP+dopamine. VIP injection produced a decrease in mean arterial pressure and an
      increase in heart rate in both spontaneously hypertensive and normotensive rats.
      Serum rPRL concentration was significantly increased at 10 minutes after
      injection. The combined therapy (VIP+dopamine) partially inhibited this response.
      Serum rLH concentration, the content of LH-RH in hypothalamic tissue as well as
      the content of pituitary LH after VIP injection in spontaneously hypertensive and
      normotensive rats did not differ from the values obtained for the control group.
      CONCLUSIONS: 1. VIP injection produced the dramatic hypotensive effects in
      hypertensive rats; 2. A marked increase in PRL concentration in response to VIP
      was partially inhibited by dopamine in hypertensive and normotensive rats; 3. VIP
      injection did not change LH-RH and LH release in both hypertensive and
      normotensive rats.

PMID- 1345536
TI  - Growth rate in children with vitamin-D-dependent rickets in relation to 1-alpha
      hydroxyvitamin D3 dosage.
AB  - Growth rate of five children with vitamin D-dependent rickets was analyzed during
      the long-term treatment with an active analog of vitamin D3. Considerable
      increase in growth rate together with the improvement of biochemical values and
      radiological pattern took place during the initial phase of administration of 1
      hydroxyvitamin D3. During the maintenance treatment of long duration with 1
      hydroxyvitamin D3 both the acceleration of growth and catch-up growth persisted.
      However, in 4 among 5 children studied an inhibition of growth was observed
      during different periods of time. Only in one boy was this connected with the
      conclusion of the process of physiological growth. In three remaining children a
      slow-down in growth rate appeared during the pre-pubertal period or was the
      effect of lowering the dose of 1-hydroxyvitamin D3 as an countermeasure to
      hypercalciuria. In such cases inhibition of growth was caused by the
      administration of too small a dose of 1-hydroxyvitamin D3 in relation to the
      requirement. In all cases the appearance of biochemical features of rickets
      aggravation, such as low blood serum phosphate concentration and elevated
      alkaline phosphatase activity, preceded the observable inhibition of growth. The
      results obtained allow us to conclude that the inhibition of growth observed
      during the long-term treatment of rickets with 1-hydroxyvitamin D3 may be
      regarded as the first signal of inadequate dosage of 1-hydroxy vitamin D3.

PMID- 1345537
TI  - [Effect of prolonged hemodialysis therapy on secretion of testosterone induced by
      luliberin in men with chronic renal insufficiency].
AB  - The effects of prolonged hemodialysis therapy on testosterone secretion have been
      studied in 41 men with chronic renal insufficiency. Fifteen healthy men served as
      control group. LH-RH stimulation test was performed in all the studied subjects.
      It was found that blood serum testosterone concentration is lowered in all the
      patients with renal insufficiency irrespective of the time of duration of
      hemodialysis therapy as compared to the control group. In patients dialyzed
      longer than 50 month testosterone level was higher than in those subjected to
      shorter period of hemodialysis therapy. Reactivity of testosterone secretion in
      LH-RH stimulation test was greater in patients dialyzed over 50 months than
      either in those dialyzed during the shorter period or in the controls.

PMID- 1345538
TI  - [Numeric description of circadian rhythm of TSH in patients with cold tumors of
      the thyroid gland before and after surgery].
AB  - Circadian rhythm of TSH was analyzed in patients with cold tumors of the thyroid
      before and after surgical removal of the tumors and in control subjects. By using
      special computer program BIOR based on harmonic and regression analysis, designed
      for verifying and comparing various biorhythms, significant differences were
      found between TSH biorhythms in patients with cold thyroid tumors before and
      after the operation.

PMID- 1345539
TI  - [Studies of the hypothalamo-hypophyseal corticoliberin system. VII. Effect of
      ether stress and dexamethasone on the hypothalamo-hypophyseal-adrenal axis].
AB  - The effect of ether stress and dexamethasone on hypothalamo-hypophyseal-adrenal
      axis was investigated in sexually mature male Wistar rats. Separate group of rats
      was subjected to ether stress during 2 minutes. The remaining animals were
      treated with dexamethasone during 7 days. CRF-immunoreactive and vasopressin
      immunoreactive neurons were detected within paraventricular nuclei and median
      eminence by using specific antibodies. Body weight of the rats as well as the
      weights of pituitary and adrenal glands were also measured. The levels of ACTH
      and corticosterone were determined in blood serum. It was found that the ether
      stress caused a considerable decrease in the amount of CRF-immunopositive
      substances in the outer layer of median eminence and a decrease in the amount of
      vasopressin-immunoreactive neurocytes in the parvocellular fragment of
      paraventricular nuclei. Dexamethasone administration caused an increase in the
      amount of CRF-immunopositive perikaryons within paraventricular nuclei and also
      an increase in vasopressin-immunopositive nerve fibers in median eminence.

PMID- 1345540
TI  - [A case associating primary parathyroid hyperfunction with hyperthyroidism].
AB  - A case of rare association of hyperparathyroidism with fully developed
      hyperthyroidism appearing in a woman 23 years old with advanced generalized
      cystic fibrosis has been presented.

PMID- 1345541
TI  - [Gastrointestinal hormones--some problems of the 90's].

PMID- 1345542
TI  - [Role of the polyol cycle and disturbances of myoinositol metabolism in
      pathogenesis of chronic complications in diabetes mellitus].

PMID- 1345543
TI  - [Prof. dr hab. med. Tadeusz Ewaryst Pawlikowski life and activity (25.X.1904
      19.IV.1985)].

PMID- 1345544
TI  - [The effect of levels of alkali salts in Alginate-LF-250 on physico-mechanical
      properties of materials used in making impressions based on irreversible
      colloids].
AB  - The aim of this paper is the examination of physical-mechanical properties of
      alginate composition regarding the change of alkali salt alginate composition in
      the limits of the presence from 8 to 20%, and after the standard ISO 1563, 1978
      (E). The combinations make homogenized mixtures of micronized powders of the
      basic component, retarders, accelerators, system stabilizators, the means for
      colloides and constituents lowering, which are prepared in the relation of 16
      gr/40ml. The change of alkali salt alginate concentration from 8 to 20% does not
      effect the working time and the time of alginate mash binding, while percentage
      of permanent deformation of the binding material is larger than the allowed
      standard after ISO 1563, 1978 (E) in case when alginate alkali salts in the
      composition are present in the smaller quantity than 12%.

PMID- 1345545
TI  - [Histologic picture of dental pulp in dogs treated with ZnOOK paste].
AB  - The activity of zinc-oxide paste on histologic changes of the pulp was examined
      while the indirect capping of the exposed dog tooth pulp was performed. The
      results showed that the histologic changes observed in dog tooth pulp were
      accompanied with hyperaemia and blood vessel dilatation then with the pulp
      oedema, slight disorder of odontoblast palisade and the presence of the traces of
      occurrence of tertiary dentin.

PMID- 1345546
TI  - [Newly discovered rotavirus serotypes in 4 years of collecting samples from
      children with diarrheal syndromes].
AB  - In the four year period from 1985 to 1988 from 527 treated patients with
      diarrhoea syndrome age 0-7 years hospitalized on Clinic for infectious disease in
      Sarajevo, 170 patients (32.2%) had rota virus isolated as the cause isolated.
      Subgrouping and serotyping of rota virus are undertaken in 115 cases. Subgrouping
      was done well in 94.7% and serotyping in 58.2% cases. Serotype 1 of subgroup II
      isolated in 58.2% of to cases during four years of work, and other serotypes were
      isolated sporadically. For the first time in Europe, during these four years
      serotype 9 rota virus isolated in 17 cases. For the first time in ex Yugoslavia
      and Republic of Bosnia and Hercegovina, and second time in Europe serotype 8 of
      rota virus has been isolated in sample of feces.

PMID- 1345547
TI  - [Hemorheologic changes in diabetes mellitus].
AB  - 78 diabetics and a healthy control group of 100 were evaluated according to their
      haemorrheological parameters (whole blood viscosity, plasma viscosity,
      aggregability and rigidity of erythrocytes). Diabetics were divided according to
      type of diabetes, quality of metabolic control and expression of microangiopathy.
      Hyperviscosity was noted in both groups of diabetics as compared to the control
      group. Changes in patients with IDDM were more pronounced in erythrocyte
      rigidity, while in patients with NIDDM they were more expressed in cell
      aggregability. These changes were present even before the clinical onset of the
      late complications of diabetes, although they were more expressed in patients
      with complications. Changes in patients with good metabolic control, were less
      expressed in comparison to those with poor metabolic control. The conclusion is
      that metabolic derangements in diabetes have an important influence on
      haemorrheological properties. Thus, reducing blood viscosity in these patients,
      may be a promising approach to improving microcirculation and delaying the
      progression of microangiopathy.

PMID- 1345548
TI  - [The effect of PUVA therapy on circulating T lymphocytes].
AB  - In this article effects of photochemotherapy on T lymphocytes of peripheral blood
      and capable lymphocytes to blastic transformation by patients with psoriasis
      generatisata were presented. No statistical changes were found in relation to
      healthy persons.

PMID- 1345549
TI  - [A mini circular external fixator--Kosevo type].
AB  - In this experiment we showed factors of interest for compression's grade after
      experimental examination. We used mini circular external fixator type Kosevo and
      showed it's employment. The conclusion that the compression's grade was 30 kp/cm2
      and depend of bone's thickness. At the end you can see clinical and medical
      economic effects of using thus fixator.

PMID- 1345550
TI  - [The Mirizzi syndrome in biliary surgery].
AB  - In the paper are 2 cases of the so called Mirizzi's syndrome presented, as a
      special clinical entity in the surgery of the biliary tract. Pablo Mirizzi
      (Cordoba, Argentina, 1948) performed the basic scientific observations, so the
      syndrome was named after him. There are 4 basic components: 1. Anatomic
      variations of the gall entrance, namely ductus cystic with the main gall canal,
      while ductus cystic has a prolonged parallel course with choleductus, 2. Impacted
      concrement in the gall throat or even ductus cystic, 3. A part of entire
      choleductus compression with extra luminar pathologic substrate, and 4. The
      consequences of the gall recurrent cholangitis, namely cholangitis cirrhosis. A
      long lasting compression of the choleductus wall due to the jammed concrement,
      sooner or later, may bring to the wall necrosis and penetration of the concrement
      into the choleductus lumen (make a bilio-biliary fistula) with all the perils.
      The mentioned circumstances, in the course of the operation being a number of
      serious post-operative complications (being obvious from the presented cases).
      Now days, a great importance is given to the Mirizzi's syndrom in the prevention
      of the post-operative complications relating to the outstanding clinical entity.

PMID- 1345551
TI  - [Evaluation of a 10-year study of family health care].
AB  - Family is fundamental component in society and place where health or disease are
      creating. Family health care in our country has not found its place yet, although
      there is reason for its development. Some experimental areas in our country,
      which were making progress in family health care, should important advantages of
      family health care are greater satisfaction of population and 6 medical staff,
      better efficiency, effectiveness, economisation and better quality of health
      care. Modification of schooling system and improving the quality of
      specialisation medical staff, modification of method of micro-organization of
      health care schools and were organisations charges in information system by using
      computers and help of society which will sanction recommended charges by law, are
      necessary for existence of family health care. That's way implementation of
      purposes of strategy "Health for all by the year 2000" of WHO is very important
      in our country, specially those purposes considering concept of family health
      care which we were experimentally developing for 10 years in Sarajevo.

PMID- 1345552
TI  - [Identification of oxymetholone metabolites in the urine using gas chromatography
      mass spectrometry].
AB  - Metabolite of 17-methyl-17-hydroxy-2-(hydroxymethylen)-androstan-3-one
      (oxymetholane) in urine after a single oral administration was monitored by gas
      chromatography+mass spectrometry. During the investigation prepared TMS-ethers
      and TMS-enol-ethers of conjugated steroid fraction two new metabolites of
      oxymetholone have been identified: tetrahydrooxymetholone and tetrahydro-6
      hydroxy-oxymetholone.

PMID- 1345553
TI  - [Morphometric characteristics of thyroid cells in irradiation-stressed rats
      treated with pinealectomy and melatonin].
AB  - The authors were investigating the qualitative and quantitative characteristics
      of the cells of the thyroid gland of pinealectomized and melatonin treated rats
      whose body irradiated with 8 Gy gamma rays. It was established that melatonin
      decreased height of the thyreocytes in peripherical and central part of gland,
      and nuclear volume of thyreocytes only in the central part of gland. The results
      suggest the role of melatonin in determination of the behaviour of thyreocytes
      upon Pinealeotomy and Radiation.

PMID- 1345554
TI  - Candida parapsilosis: epidemiology, pathogenicity, clinical manifestations, and
      antimicrobial susceptibility.
AB  - Early reports associated Candida parapsilosis with endocarditis in intravenous
      narcotic addicts. More recently, this species has emerged as an important
      nosocomial pathogen, with clinical manifestations including fungemia,
      endocarditis, endophthalmitis, septic arthritis, and peritonitis, all of which
      usually occur in association with invasive procedures or prosthetic devices.
      Outbreaks of C. parapsilosis infections have been caused by contamination of
      hyperalimentation solutions, intravascular pressure monitoring devices, and
      ophthalmic irrigating solution. Experimental studies have generally shown that C.
      parapsilosis is less virulent than Candida albicans or Candida tropicalis.
      However, characteristics of C. parapsilosis that may relate to its increasing
      occurrence in nosocomial settings include frequent colonization of the skin,
      particularly the subungual space, and an ability to proliferate in glucose
      containing solutions, with a resultant increase in adherence to synthetic
      materials. Recently developed molecular techniques may facilitate the continued
      exploration of the epidemiology and pathogenesis of C. parapsilosis infections.

PMID- 1345555
TI  - Health effects of Halon 1301 exposure.
AB  - An accidental discharge of a Halon 1301 system is reported. Thirty-one workers
      were assessed, 22 who were present at the time of the discharge, and 9 who worked
      the next shift. The incident was complicated by a small Freon-22 leak several
      hours later. Throat, eye, and nasal irritation and lightheadedness were reported
      by the majority of workers. Workers present during the halon discharge reported
      significantly more lightheadedness, headache, voice change, cough, and a fast
      heartbeat than did those who worked the later shift. These differences were
      significant even after correcting for confounding factors such as age, sex, and
      sense of anxiety at the time of the incident. The possible causes for the
      irritant symptoms include breakdown products of Halon 1301 and Freon-22 or
      contaminants from the halon discharge system. Although these irritant effects may
      not be an effect of Halon 1301 alone, they may occur in these discharge
      situations, and workers should be advised of this possibility. The possible
      cardiac and central nervous system effects also should be considered. The
      importance of a clear-cut protocol to deal with such incidents as well as worker
      education are discussed.

PMID- 1345556
TI  - The quality of nutrition articles in Free Radical Biology & Medicine.

PMID- 1345558
TI  - [Muscle antigens recognized with autoantibodies in patients with Graves'
      ophthalmopathy].
AB  - The aim of this work was to characterise the eye muscle antigens reacting with
      autoantibodies from Graves ophthalmopathy patients to elucidate the function of
      these antibodies. As estimated by ELISA test antibodies of IgG class reacting
      with porcine microsomal membranes are present in about 25% of patients while of
      IgM class in about 15% of patients with Graves ophthalmopathy. Their presence do
      not correlate with ophthalmopathy index, neither they have relation to treatment.
      Anti eye muscle antibodies were present at some stages of the disease in three
      patients who develop ophthalmopathy, from the group of 26 patients treated during
      one year for hyperthyroidism. However, sporadically these antibodies were found
      also in about 20% of patients with Hashimoto disease, Lupus erythematosus or
      Scleroderma. Some of them cross react with antigens of skeletal muscle and liver.
      Eye muscle antigens reacting with patients antibodies are localised in plasma
      membranes and in membranes of smooth reticulum. Affinity purification of
      solubilised porcine eye muscle membrane proteins on a column with immunoglobulins
      from pooled serum of patients resulted in 23 fold purification of the antigen.
      The sensitivity of ELISA was not significantly increased by the use of affinity
      purified antigen, however some of previously negative ophthalmopathy sera gave
      positive reaction. Porcine eye muscle membrane proteins were separated by SDS
      PAGE and transferred to nitrocellulose. The reactions of electroblotted proteins
      with sera from patients with Graves ophthalmopathy and also sera from healthy
      controls shown very complex pattern. There was not a single antigen or antigens
      reacting only with antibodies present in sera of ophthalmopathy patients and not
      in controls. Patients sera reacted more often than control sera with an antigen
      of about 40 kDa. The reaction of sera from some patients with proteins about 100,
      70 and 65 kDa were stronger than between these proteins and control sera. No
      changes in the pattern of reaction between antibodies and eye muscle antigens
      were noticed in serum of the same Graves' patient with or without ophthalmopathy
      during one year follow up and treatment, regardless of clinical course of the
      disease. When human eye muscle membrane fractions from tissue obtained during
      strabismus repair or at autopsy was used for immunoblotting, smaller number of
      proteins reacted with autoantibodies. Again there was no single antigen or
      antigens reacting with antibodies from sera of all Graves ophthalmopathy
      patients. Sera of some patients reacted with antigens about 50 kDa, not
      recognized by controls. The results of present study show, that the anti eye
      muscle antibodies are present in some of Graves ophthalmopathy patients.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1345557
TI  - Cross-cultural patterns in eating disorders: a review.
AB  - Eating disorders were previously thought to be isolated to achievement-oriented,
      upper and middle class individuals in Western countries. It now appears that
      these disorders may be increasing in other sectors of society and in a number of
      diverse cultural settings. We review the studies that comprise the relevant cross
      cultural research literature on eating disorders. We also discuss the changing
      cultural factors that may be contributing to the apparent increase in these
      disorders around the world and directions for future research on such factors.

PMID- 1345560
TI  - [Endocrinologic limits].

PMID- 1345559
TI  - [The effect of monotherapy on concentration of selected blood serum hormones and
      upon cognitive function of children with epilepsy].
AB  - The studies included 64 children with newly diagnosed epilepsy, aged from 6 to 15
      years of life. In 25 children with partial and secondary generalized seizures
      monotherapy with carbamazepine was introduced; in 19 children with primary
      generalized seizures--with phenobarbital, and in patients with both types of
      seizures--with primidone. Monotherapy was controlled by means of blood serum drug
      concentration level monitoring; the therapy was successful in all the children.
      The group did not include patients with mental retardation, and epilepsy was
      idiopathic. Prior to the institution of treatment, a single determination of
      blood serum triiodothyronine, thyroxine, TSH, prolactin, cortisol, LH and
      testosterone was made. Psychological test were carried out employing Wechsler's
      scale, Bender-Santucci test, rhythmic structures developed by Mira Stambak and
      test of manual dexterity (card display). In order to evaluate short-term effects
      of the employed drugs upon the blood serum concentration values of the studied
      hormones, a repeated determination was made one month after the initiation of
      therapy. The third determination was made one year after the onset of treatment
      in order to assess the long-term effects. The effect of drugs upon their
      cognitive functions was assessed in a follow-up psychological testing performed
      after one year of therapy. The studies combined with statistical analysis led to
      a conclusion that after one month of monotherapy there occurred a significant
      drop in thyroxine concentration levels, still augmented after one year. Patients
      treated with carbamazepine showed a significant decrease of T3 levels after one
      month and one year, whereas treatment with phenobarbital and primidone did not
      result in significant changes of T3 concentration. Yet, T3 and T4 concentration
      values did not exceed normal limits. No type of monotherapy resulted in
      significant long-term changes of TSH concentration levels. No clinical signs of
      hypothyroidism nor goiter were observed in the studied children. After one month
      of monotherapy with carbamazepine and phenobarbital there was observed a
      significant increase of prolactin and cortisol levels, which was absent after one
      year. The values observed did lie within normal limits. No significant changes
      were observed with respect to the effect of the studied drugs upon blood serum LH
      and testosterone levels. After a one-year monotherapy with primidone the children
      revealed a significant improvement of results measured on performance scale and
      by means of a full Wechsler scale. Carbamazepine and phenobarbital did not affect
      the intelligence quotient of the studied children.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1345561
TI  - [Superiority of magnetic resonance imaging (MRI) over computerized tomography
      (CT) in diagnosis of hypopituitarism].
AB  - Hypopituitarism can be a result of various lesions of hypothalamus, pituitary
      stalk, or of the pituitary gland itself. The aim of the study was to assess the
      value of CT and MRI examinations in determination of the cause of
      hypopituitarism. Seventeen patients with hypopituitarism (9 women and 8 men) aged
      22 to 61 years have been examined. In three cases growth deficiency was observed,
      4 women had galactorrhoea, 4 patients had diabetes insipidus, 16 patients had
      supra-adrenal insufficiency, 14 had signs of hypogonadism and 10 hypothyroidism.
      In each case plasma concentrations of LH, FSH, PRL, TSH, alpha-subunit, ACTH
      before and after appropriate stimulation with TRH, metoclopramid, LH-RH, GRF or
      metyrapon were determined with RIA. Every patient was examined both with CT and
      MRI (0.5 T Toshiba MRT 50a). All 17 patients had abnormal MR images of
      hypothalamo-pituitary area, while only 10 of them had abnormalities in their CT
      scans. In remaining 7 patients the MRI revealed: three cases of congenital
      malformation of hypophyseal stalk, two cases of empty sella, one posttraumatic
      lesion of the stalk and one case of granulomatous infiltration of the stalk. We
      found MRI superior to CT in establishing the case of hypopituitarism.

PMID- 1345562
TI  - [A case of pituitary stalk tumor diagnosed with magnetic resonance (MRI)].
AB  - Authors present a case of 28-year old female with anterior hypopituitarism and
      diabetes insipidus, with properly functioning anterior pituitary cells as showed
      by means of measuring pituitary hormones in response to neurohormones i.v.
      injections. Magnetic resonance imaging revealed neoplastic tissue in the
      pituitary stalk destroying supraopticohypophysial and paraventriculohypophysial
      tracts, as well as portal blood system, thus preventing release of vasopressin
      and these hypothalamic neurohormones from accessing anterior pituitary.

PMID- 1345564
TI  - New long-acting bromocriptine (Parlodel MR and Parlodel LAR) in the treatment of
      pituitary tumours with hyperprolactinemia.
AB  - In order to assess the efficacy and tolerability of new long acting
      bromocriptine: Parlodel MR (oral form) and Parlodel LAR (injectable form suitable
      for repeatable administration) 40 patients (29 women and 11 men) with pituitary
      tumours with hyperprolactinemia (PRL 70 micrograms/l) were investigated in a
      double blind study. Patients were divided into 2 groups of 20. In the first group
      Parlodel R or Parlodel MR in equivalent doses was given, the other group was
      administered Parlodel R or Parlodel LAR. During the next 6 months 20 patients
      were treated with Parlodel MR and the other 20 with Parlodel LAR. In all patients
      pituitary and peripheral hormones, CT scan and visual fields were examined before
      and after 28 days of bromocriptine treatment. During the next six months 20
      patients were treated with Parlodel MR while the other 20 with Parlodel LAR.
      Serum PRL fell in all patients and values in the normal range were obtained in 36
      patients. In 30 out of 35 patients with signs of pituitary tumour in CT scan, a
      significant tumour shrinkage was observed. Most patients achieved considerable
      clinical improvement: disappearance of galactorrhoea, resumed menses in women,
      increased potency in men. There were no difference in efficacy in Parlodel R,
      Parlodel MR and Parlodel LAR, but in the case of Parlodel LAR the least number of
      side effects was found. Treatment with long acting bromocriptine-Parlodel MR and
      LAR of patients with pituitary tumours with hyperprolactinemia is an efficacious,
      safe and better tolerated method than Parlodel R treatment.

PMID- 1345563
TI  - Increased plasma VIP concentration in patients with prolactinoma.
AB  - Vasoactive intestinal polypeptide (VIP) is now considered to be a prolactin
      releasing factor (PRF). The aim of this study was to determine the VIP
      concentration in peripheral blood in patients with prolactin-secreting adenoma
      compared to healthy subjects. We also examined the effect of bromocriptine
      administration on the plasma VIP concentration in patients with prolactinoma.
      Nine patients with prolactinoma (6 women and 3 men, aged 27-50) and 7 healthy
      control subjects (4 women and 3 men, aged 26-40) were examined. Blood samples for
      prolactin and VIP were collected at 06:00, 12:00, 18:00, 24:00. In prolactinoma
      blood was taken before and after bromocriptine administration. Serum prolactin
      concentration was determined by the radioimmunoassay. VIP concentration was
      measured by a specific radioimmunoassay Kit-INCSTAR Corp. (Minnesota, USA).
      Statistical significance was calculated using the analysis of variance. A single
      5 mg oral dose of bromocriptine decreased the mean prolactin concentration during
      the first 24 hours of treatment. Plasma VIP concentration was higher in
      prolactinoma patients compared to healthy subjects. There was no change in plasma
      VIP level after bromocriptine administration. IN CONCLUSION: in patients with
      prolactin secreting adenoma the plasma VIP concentration is increased.

PMID- 1345565
TI  - Mixed pituitary tumours--effects of bromocriptine treatment: Parlodel MR and
      Parlodel LAR.
AB  - Majority of pituitary tumours secrete one of the named hormones: PRL, GH, ACTH,
      proopiomelanocortine, alpha and beta subunit of TSH, LH, and FSH. Some of those
      tumours secrete two or more hormones. The aim of this study was to determine the
      effect of bromocriptine (Parlodel MR and LAR) upon secretion of hormones and
      tumour size in 10 patients with mixed pituitary tumours. In all patients
      pituitary and peripheral hormones, CT scan and visual fields were examined before
      and after treatment with bromocriptine: Parlodel MR and LAR. Bromocriptine
      treatment decreased PRL secretion in all 10 patients; GH--in all 6 in whom it was
      increased; TSH--in 2, FSH--in 2 and alpha-subunit in all 6 in whom they were
      increased. In 5 patients treatment resulted in shrinkage of the tumour mass by 20
      to 35%. In all examined subjects clinical improvement was achieved. Our results
      demonstrate that bromocriptine (Parlodel MR and LAR) is very effective and well
      tolerated in the treatment of patients with mixed pituitary tumours particularly
      those with hyperprolactinemia.

PMID- 1345566
TI  - The effect of oral ethanol ingestion on the diurnal neurotensin secretion in man.
AB  - Neurotensin is a tridecapeptide, present in the central nervous system and the
      gastrointestinal tract in man and animals. The affect of orally administered
      ethanol (1 g/kg body weight) on the neurotensin secretion over 24 hr period was
      studied in eight young healthy men. No significant circadian rhythm of
      neurotensin secretion was detected in the eight subjects studied. Ethanol
      produced a progressive rise in the plasma level of neurotensin reaching a maximum
      at 12:00 (13.8 +/- 8.6 pmol/l). At 12:00 and 14:00, the neurotensin
      concentrations were significantly higher than on the placebo day (p < 0.05). The
      secretion rate of neurotensin was determined approximately using the area under
      the curve method. Ethanol produced a transient rise in neurotensin secretion over
      the first 12 hrs period (08:00-20:00 h) after its administration (p < 0.02). The
      observation that ethanol increases transiently the neurotensin secretion in man
      supports the hypothesis that neurotensin may be involved in the biological effect
      of ethanol. The source of its secretion remains to be elucidated.

PMID- 1345567
TI  - [Results of 3-stage treatment: (I) corticotherapy, (II) linear acceleration and
      (III) orbital decompression in 206 patients with malignant Graves
      ophthalmopathy].
AB  - There is no, so far, a rational method of therapy based upon the etiology of
      autoimmune Graves' ophthalmopathy. As a malignant Graves' ophthalmopathy we
      defined the most severe eye changes leading to the sight loss or permanent
      disability of vision which are classified as exceeded class 3c according to the
      eye changes classification of the American Thyroid Association [27]. The aim of
      the study was to develop the most efficacious method of therapy for malignant
      Graves' ophthalmopathy. The material consisted of 206 patients treated according
      to the 3-stage method: 1-st--corticotherapy, 2-nd--radiotherapy, including linear
      accelerator, 3-rd--orbital decompression. Moreover, in four patients
      plasmapheresis was applied and in additional five cyclosporine was administered.
      In all 206 patients the estimation of the results of the treatment was based on
      the Donaldson ophthalmopathy index [4]. It has been proved that corticotherapy
      combined with linear accelerator radiotherapy has been the most efficacious
      method of treatment. It has also the least number of side effects. Orbital
      decompression as the 3-rd stage of treatment was employed in those cases in which
      the previous two stages of medical therapy were unsuccessful.

PMID- 1345568
TI  - [Relationship between clinical classification of hyperthyroidism for three grades
      of severity and level of triiodothyronine (T3) and thyroxine (T4) concentrations
      in serum].
AB  - The aim of the study was to assess the relationship between the clinical
      classification of hyperthyroidism based on the 3-degree score system and T3 and
      T4 serum concentration. 161 patients with Graves disease or toxic goiter were
      studied. By comparing the number of scores separating the 3 subgroups in relation
      to the severity of disease with T3 and T4 serum concentration of tyreotoxic
      patients we found a very high statistically significant correlation. We also
      found the marked (by +50%) statistically significant increase in the serum T3
      concentration related to the degree of hyperthyroidism severity.

PMID- 1345569
TI  - [Treatment of hypothyroidism with L-thyroxin].
AB  - To compare an efficacy of the galenic form of desiccated thyroid gland-
      Thyreoideum "Polfa" with the synthetic L-thyroxine (Eltroxin Glaxo) in the
      treatment of hypothyroidism 15 patients were investigated. In all 15 cases before
      and after treatment ECG and the serum concentrations of cholesterol, thyroxine
      (T4), triiodothyronine (T3) as well as thyrotropin (TSH) in response to TRH were
      performed. After the treatment with Thyreoideum "Polfa" in doses 0.2 to 0.6
      mg/daily there were neither clinical improvement, normalization of ECG, the serum
      concentrations of cholesterol, T3, T4 nor TSH. However, after the L-thyroxine
      treatment (Eltroxin Glaxo) in doses 100 to 200 micrograms/daily the clinical
      signs of hypothyroidism disappeared in all 15 patients. In ECG the statistically
      significant increase in voltage of the R and T waves after L-thyroxine treatment
      were observed. Also a significant decrease in the serum concentration of
      cholesterol and an increase in T4 and T3 were found. The serum concentration of
      TSH in response to TRH after the L-thyroxine treatment significantly decreased. L
      thyroxine appeared to be a very efficacious in the treatment either primary or
      secondary hypothyroidism.

PMID- 1345570
TI  - [Anaplastic thyroid carcinoma developed after treatment of "hot" thyroid nodule
      with radioiodine].
AB  - A case of 55 years old woman with "hot" right lobe toxic thyroid nodule,
      presenting with paroxysmal atrial fibrillation, and therefore treated with 131I
      666MBq (18 mCi) is described. After six years she became pyrexic and suffered of
      severe cough proxyisms. The fine needle biopsy of the above nodule showed the
      presence of anaplastic thyroid carcinoma. Strumectomy followed by local
      radiotherapy resulted in complete disappearence of all symptoms. The microscopic
      of the removed thyroid tissue confirmed the above diagnosis. After 22 months'
      observation the patient remained in good general condition. The possible reasons
      for the development of the thyroid carcinoma in this case are discussed.

PMID- 1345571
TI  - A correlative study between cortisol and ACTH in Cushing's disease following
      bilateral adrenalectomy and in Nelson's syndrome.
AB  - Correlation analysis was used to investigate the interrelation between plasma
      ACTH and serum cortisol concentrations determined at 8:00, 12:00, 16:00 and 22:00
      h in 48 patients bilaterally adrenalectomized for Cushing's disease, including 23
      patients with a pituitary adenoma (Nelson's syndrome). In the patients without
      evidence of a pituitary adenoma a significant inverse correlation was found at
      8:00, 16:00, 22:00 h and additionally when all the pairs of estimations were
      analyzed. In a full-blown Nelson's syndrome an inverse correlation was not proved
      (p = 0.05). During remission in Nelson's syndrome an inverse correlation between
      cortisol and ACTH concentrations was stated at 8:00 h and after the evaluation of
      all the pairs of estimations. The results of our studies have shown that
      exogenous cortisol exerts a partial inhibitory action on ACTH secretion in
      patients bilaterally adrenalectomized for Cushing's disease. In active Nelson's
      syndrome this influence is questionable, it comes however into prominence during
      remission.

PMID- 1345572
TI  - Incidentally found adrenal tumours: results of investigation of the pituitary
      adrenal axis.
AB  - In the last 7 years 64 patients (48 women, 16 men, aged 25-75 yrs) with
      incidentally found asymptomatic adrenal tumours have been observed in the
      Department of Endocrinology. In 11 patients a routine clinical investigations
      revealed metastatic tumours at the adrenal glands. In the remaining 53 patients
      the diameter of the adrenal tumours was < or = 3 cm. Only two of them were
      treated surgically; the rest has been observed regularly and ultrasonographic
      examinations have been repeated every 3 to 6 months. Twenty three patients with
      adrenal tumours < 3 cm of diameter were treated by surgery. The macroscopical
      examination revealed adrenal cortical adenoma in 11 cases, adrenocortical
      carcinoma in seven, and pheochromocytoma in 5 patients. The investigation of the
      pituitary-adrenal system (urinary excretion of 17-OHCS before and during
      dexamethasone administration, 17-KS, "free" corticosteroids, plasma ACTH,
      cortisol and S-DHA levels) did not reveal any abnormality except that in 10
      patients the plasma ACTH concentration was low, especially in the morning. These
      values were significantly lower as compared with the remaining patients and with
      control group. One of the possible interpretations is a pituitary suppression by
      only periodically increased concentrations of the corticosteroids.

PMID- 1345573
TI  - [Primary hyperaldosteronism suppressed after glucocorticoid administration].
AB  - Authors present a case of glucocorticoid suppressible hyperaldosteronism in 18
      year old female. Unmeasurable low plasma renin activity and marked increase in
      aldosterone concentration was established. After administration of dexamethasone,
      normalization of aldosterone concentration and blood pressure has been observed.

PMID- 1345574
TI  - Lower 24-hour growth hormone levels in type I diabetics responding to thyrotropin
      releasing hormone (TRH).
AB  - The aim of the study was the evaluation of growth hormone secretion under
      physiologic conditions in two groups of type I diabetics: responding and
      nonresponding to TRH stimulation. Both groups matched for age and metabolic
      control of diabetes were studied during 24-hours and after GHRH stimulation. The
      whole diabetic group (n = 18) showed circadian rhythm of GH secretion with mesor
      value of 4.03 micrograms/l. TRH-responders had lower mesor GH value than TRH
      nonresponders: 3.53 vs. 5.32, p < 0.05. GH response to GHRH was almost identical
      in both groups. C-peptide level was lower in TRH-responders: 0.16 vs. 0.56
      microgram/l, p < 0.05. No correlation was found between growth hormone response
      and HbA1 and C-peptide levels. It is concluded that type I diabetics responding
      to TRH stimulation are characterized by lower mean 24-hour GH levels and lower C
      peptide values.

PMID- 1345575
TI  - Thyrotropin-releasing hormone (TRH) does not suppress growth hormone response to
      L-dopa in insulin-dependent diabetes mellitus.
AB  - Thyrotropin-releasing hormone (TRH) blunts growth hormone (GH) response to
      various stimuli in normal subjects. We were interested if similar inhibitory
      effect of TRH could be demonstrated in diabetes mellitus where GH is abnormally
      regulated. In this study we compared the effect of TRH on GH response to L-dopa
      in normal and diabetic subjects. TRH 0.2 mg iv blunted GH response to L-dopa 0.5
      g p.o. in normal subjects with peak GH values 13.1 and 7.3 micrograms/l, p <
      0.05. In the diabetics no inhibitory effect of TRH was demonstrated and GH was
      even paradoxically increased after TRH: 14.9 and 21.9 micrograms/l, p = NS. Lack
      of inhibitory effect of TRH was more pronounced in patients with proliferative
      retinopathy. It is concluded that TRH has no inhibitory effect on L-dopa-induced
      GH response in diabetic subjects. This finding provides further evidence for
      disturbed GH regulation in diabetes mellitus.

PMID- 1345576
TI  - Measurement of bone mineral density (BMD) with quantitative computed tomography
      (QCT) in postmenopausal osteoporosis: effect of estrogen.
AB  - To determine the efficacy of the estrogen replacement therapy (ERT) on the bone
      mineral density (BMD) measured with quantitative computed tomography (QCT) in
      postmenopausal osteoporosis 16 women aged 46-72 were examined. They were divided
      into two groups: 8 women treated with conjugated estrogens (Group I) and 8 who
      did not received ERT (Group II). In all 16 patients the serum hormonal
      concentrations (LH, FSH and estradiol) were measured with radioimmunological
      methods. The bone densitometry was performed in all of them using the single
      energy computed tomography (QCT) with the computer Picker 1200. Bone mineral
      density was measured in three lumbar vertebra (L1-L3) and expressed in milligrams
      K2HPO4 per ml. The bone mineral density (BMD) was statistically significantly
      higher in the estrogen treated group (Group I) in every vertebra compared with
      that of controls (Group II). The serum FSH concentration was statistically
      significantly lower in the ERT group (Group I) and a statistically significant
      correlation between FSH level and average BMD (Lmean) was present. IN CONCLUSION:
      1. the ERT is very efficacious in preventing bone loss in postmenopausal women;
      2. measurement of BMD in lumbar vertebra L1 or L3 may be a sufficiently reliable
      and accurate, cost-effective and time-saving method of screening for
      osteoporosis; 3. the serum FSH determination seems to be useful in monitoring of
      the estrogen therapy for postmenopausal osteoporosis.

PMID- 1345577
TI  - [Osteoporosis definition, prevention and treatment].

PMID- 1345578
TI  - [Time-resolved fluorescence of europium ions and its application for
      determination of biologically active substances].
AB  - At present radioimmunoassay is still one of the most widely used analytical
      procedure. It is, however, continuously challenged by a number of non-isotopic
      techniques. This article reviews the measurement of europium chelates with high
      sensitivity using time-resolved fluorescence and its use as labels in
      immunoassays of protein and peptide hormones, haptens, virus antigens and for
      detection of inborn metabolic errors. It can be concluded that the time-resolved
      fluorescence detection of lanthanides and their chelates has been applied in a
      wide variety of both routine and research application. This technique is
      anticipated to gain wide use for measurement of numerous anylates of different
      origin. In immunoassays time-resolved fluorometry is one of the most promising
      alternatives available in the non-isotopic field.

PMID- 1345579
TI  - [Incidence of goiter in children of the Tarnobrzeg district and environmental
      factors].
AB  - A group of 1897 school children from Tarnobrzeg district were examined out of
      this number 1241 (65.4%) children displayed goiter. Goiter incidence was also
      established depending upon age and sex. The analysis also included goiter
      incidence in relation to its size according to the WHO classification. In certain
      patients, newborns and their mothers, determinations of iodine excretion were
      made; the values were found to be within the normal. This range suggests that
      other etiological factors than iodine deficiency might possibly contribute to
      goiter development in the studied children.

PMID- 1345581
TI  - [Prevalence of goiter in children of the Poznan province].
AB  - The aim of our study was the evaluation of goiter prevalence in the children in
      Poznan and surrounding towns and villages. In 3065 children 4-16 years old the
      thyroid size and serum concentration of T3, T4 and TSH were determined. Our
      results indicate that the goiter prevalence in the group of investigated children
      was 20%. We also observed that the changes in the concentration of thyroid
      hormones and TSH were not associated with the clinical symptoms of thyroid gland
      dysfunction.

PMID- 1345580
TI  - [Changes in laboratory parameters of thyroid function in children with simple
      goiter from the Mazovia region].
AB  - Endocrinological Out-Patients Clinic at Children's Hospital in Dziekanow Lesny
      takes care of the children from Mazovia region. Hormonal findings in children
      with simple goiter were analyzed in several groups of patients. In all those
      patients preferential T3-secretion and decreased T4 production was found. These
      findings allow to conclude, that in Mazovia region there is iodine deficiency,
      which is probably the main cause of goiter development.

PMID- 1345582
TI  - [Goiter prevalence in children and adolescents in Lower Silesia in the years 1985
      1990].
AB  - Investigations of the goiter prevalence in children, aged from 0 to 18 years of
      age living in Lower Silesia were performed. The children were our clinic
      outpatients in the years 1985-1990. A separate analysis of children from each of
      the four districts was made because of a different geographical structure. The
      highest number of goiter was observed in the Wroclaw district. In the year 1983
      1989 an increase number of newly diagnosed goiter was cases observed in all
      analyzed districts, than from 1989 to 1990 a decrease, tendency in goiter
      prevalence was noticed except in Wroclaw district where the number of cases was
      stable. In the adolescent period the number of cases with newly diagnosed goiter
      increased with higher frequency among the girls.

PMID- 1345583
TI  - [Frequency of goiter in children and adolescents in the Szczecin region].
AB  - The study was carried out in 2153 children and adolescents (1066 girls and 1087
      boys) aged 5-20 years. The examined group was chosen randomly, according to a
      simple drawing scheme. The aim of the study was to evaluate frequency, size and
      character of goiter in developmental age population in Szczecin's region. The
      goiter was found in 14% of examined population (18.4% in girls and 9.8% in boys).
      Frequency of goiter approximated to 37% in girls and 16% in boys during puberty
      spurt (between 10 and 16 year of age). Small degree of thyroid enlargement was
      predominant in examined population. Large goiter was present more frequent in
      girls than in boys. We did not find clinical symptoms of thyroid gland
      dysfunction in examined group. Frequency of nodular goiter was 7% of children's
      and adolescent's population with higher incidence in boys (9%) than in girls
      (6%).

PMID- 1345584
TI  - [Goiter in school children from the Rzeszow district].
AB  - 14481 children at the age of 6 to 15 including 7242 boys and 7239 girls underwent
      the examination. Children from rural areas were the majority-12240. Goiter was
      classified according to WHO scale from 1974. Goiter was find in 4354 children
      (1790 boys and 2384 girls), which constituted 30.1% of examined group. Small size
      goiter was predominant. O-B goiter was found in 2588 children, I. in 1299, II. in
      386 III. in 81. Mielec region deserves special attention because goiter was
      diagnosed there in 49.3% of all examined children. Iodine deficiency seems to be
      the primary reason for goiter endemy.

PMID- 1345585
TI  - The relationship between autoimmune thyroid disease and iodine intake: a review.
AB  - There is evidence to suggest that elevated levels of iodide in the diet are
      associated with autoimmune thyroid disease (ATD) in susceptible individuals, and
      that autoimmune thyroiditis (Hashimoto's disease) is less common in susceptible
      individuals who live in regions with dietary iodine deficiency. There are
      epidemiologic studies in endemic goiter areas that report an increase in ATD,
      particularly thyroiditis, after the therapeutic administration of iodized salt,
      bread and oil. Lymphocytic infiltration of the thyroid is rarely found in
      patients from severe endemic goiter regions, yet there is a reversal of this
      observation after dietary iodine supplementation. Thyroid antibodies, both
      thyroglobulin (TgAb) and peroxidase (TpAb) or microsomal, were not detected in
      serum from patients with endemic goiter, but became positive in 43% of subjects
      three and six months after therapy with iodized oil, and there developed
      transient hyperthyroidism. Similarly, the addition of iodine to the diet or the
      administration of iodine-containing medications increases the frequency of ATD
      and the severity of existing autoimmune thyroiditis. Furthermore, autoimmune
      thyroiditis has been induced by the administration of excess iodide to strains of
      chickens and rats that are genetically predetermined to develop the disease. We
      are beginning to understand the pathogenesis of ATD. In hyperthyroidism the
      evidence clearly supports the hypothesis that TSH receptor antibodies (TRAb)
      stimulate the TSH receptor to induce excessive and sustained secretion of thyroid
      hormones. Cellmediated immune mechanisms, such as antibody dependent cellmediated
      cytotoxicity (ADCC), initiate the lymphocytic infiltration and thyrocytotoxicity
      in autoimmune thyroiditis. The mechanisms that initiate the development of the
      abnormal immune response and the relationship of ATD with excess iodide are
      poorly understood. There is evidence that an increase in the iodination of
      thyroglobulin (Tg) enhances its immunogenicity. The results of clinical and
      experimental studies support the requirement of a genetic predisposition to the
      development of ATD that may be precipitated by exposure to certain environmental
      factors. Another mechanism supported by experimental data is the direct toxic
      effect of excess iodide on iodide-deficient thyroid glands. High concentrations
      of iodide after oxidation to iodine causes epithelial necrosis and inflammation
      associated with lipofuscin accumulation suggestive of toxicity mediated by lipid
      peroxidation from excessive amounts of free radicals. The epithelial damage would
      initiate inflammatory and immune responses. Although these mechanisms would
      relate to the onset of autoimmune thyroiditis on exposure to excessive amounts of
      iodide, the relationship of iodide intake and autoimmune hyperthyroidism is less
      clear.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1345586
TI  - [Goiter in school children from the Swietokrzyski region].
AB  - 5982 of children living in Kielce district, aged 6.5-14.5 years were randomly
      selected for the study. The size of the thyroid gland was examined clinically. In
      some children the estimation of serum T3, T4 and TSH was performed, as well as
      iodine urine excretion. The iodine content in drinking water was also measure.
      The results of the study show that the Kielce district belongs to the mild degree
      of iodine deficiency. The verification of the iodine prophylaxis in this region
      is necessary.

PMID- 1345588
TI  - [Catalytic method of iodide ion determination in urine].
AB  - Kinetical catalytic method of iodide determination in urine was described. After
      wet ashing process in chloric/perchloric acid mixture kinetics of the trace
      iodide catalyzed reaction, cerium IV arsenic III was investigated. On the basis
      of nonlinear calibration curve determination of urine iodide in the range 0.1-5
      microM/l was possible. High sensitivity range of iodide concentration and
      simplicity of performance predestinate described method for epidemiological
      studies in iodide deficiency regions.

PMID- 1345587
TI  - Problems of iodine and thiocyanate in domestic animals in goitrogenic areas of
      southern Poland.
AB  - High incidence of goitre in human together with low level of iodine in water and
      cow milk have been observed in Southern Poland (Table I). Therefore, iodine
      deficiency was considered as the only cause of goiter development. The
      correlation coefficient between iodine concentration in water and cow milk was r
      = 0.76 (Fig. 1) and indicate the possibility of iodine determination in milk
      instead of water. The iodine determination in milk reflects the level of iodine
      in water as well as in food, a negative correlation has been obtained between
      goitre incidence in human and iodine concentration in water (r = 0.43) (Fig. 2.).
      A low correlation coefficient suggest that iodine is not a solely factor
      responsible for goitre development. Studies on cows have indicated that
      thiocyanate may have effect on goitre development as well. There has been found
      higher concentration of thiocyanate (SCN) in blood plasma and in enlarged
      thyroids (Table II). Thiocyanate belongs to goitrogenic compounds and its main
      source are the plants of Brassica species widely cultivated in southern Poland.
      It has been found that cows fed with Brassica plants have high level of SCN both
      in blood and milk with no alteration of plasma iodine level. The transfer of
      iodine from plasma to milk is only slightly affected (Table III). The level of
      SCN in the thyroid depends on its plasma concentration; the calculated
      correlation coefficient is r = 0.88 (Fig. 3). Enhanced thyrotropin (TSH)
      secretion (during goitrogenesis) may be accompanied by increased accumulation of
      SCN in the thyroid (like iodide) and reduced oxidation to SO4 (unlike iodide)
      (Fig. 4). Therefore we postulated that TSH may be partly responsible for
      increased SCN level in goitrous thyroids. The question arise whether increased
      ingestion of SCN does really potentiate iodine deficiency and goitrogenic process
      in animals breeding in southern Poland. For explanation some additionally
      experiments were performed on laboratory animals. It have been observed that
      enhanced level of plasma SCN following feeding with Brassica plants increased
      proportionally the goitrogenic action as well as the accumulation of 131J by the
      thyroid and its conversion into organic form (Fig. 5). The latter data was
      confirmed by positive correlation between thyroxine and plasma SCN levels in
      sheep (r = 0.49), (Fig. 6) Thiocyanate like other monovalent anions suppress
      goitrogenic effect of propylthiouracil. However, anti-goitrogenic properties of
      SCN depends on normal iodine ingestion (Fig. 7).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1345589
TI  - [Dietary iodine intake in children and clinical and biochemical features of
      iodine deficiency in chosen districts of south-east Poland].
AB  - The study on the effects of Czarnobyl accident on thyroid gland function in
      children (MZ XVII program) revealed a high incidence of goiter in the population
      of children in district Krakow and Nowy Sacz. Other study on Tarnobrzeg
      population showed that the frequency of goiter in school children was 67%. The
      goiter prevalence, urine iodine excretion and iodine food consumption in the same
      populations were compared. The detailed investigation of iodine intake in
      children by feeding questionnaire shows a low consumption of iodine. The urine
      iodine excretion in the population of Krakow-district was low, but higher than in
      Nowy Sacz-district and nearly normal in Tarnobrzeg. High frequency of goiter in
      children and of IDD in newborns screened for CH, as well as low urine iodine
      excretion, together with low iodine intake with food are the markers of iodine
      deficiency in Krakow and Nowy Sacz districts. The improvement of feeding as well
      as iodine salt supplementation is necessary. The situation in Tarnobrzeg district
      looks differently and needs additional study.

PMID- 1345590
TI  - Genetics of dermatophytes.
AB  - By the end of 60s a team of scientists has started at Medical Faculty of Olomouc
      the research of micromycetes pathogenic for both the humans and animals. In this
      study, the appropriate results are summarized as concerned with the genetics of
      dermatophytes. Among these results, those significant in deeper assessing the
      biology of dermatophytes and etiopathogenesis of dermatophytoses have been
      selected. In our opinion, they may be of interest for the successors in the
      direction mentioned. Here are also formulated certain open problems and the
      applicative outputs are traced, for example, those concerning with vaccines. The
      approaches used, even unusual in the medical mycology from a traditional scope,
      are believed to prove the convenience of genetic methods when researching
      mycopathogens. We regret to miss at the edition of this publication the late
      founder of the team, RNDr. Nora Hejtmankova, CSc. which had the greatest
      contribution to the Chapters on the karyology and variability of dermatophytes as
      well as to the hybridization analysis of Trichophyton mentagrophytes complex.

PMID- 1345591
TI  - Interferon induction in porcine leukocytes with transmissible gastroenteritis
      virus.
AB  - Leukocytes were harvested from the peripheral blood, mesenteric lymph node and
      small intestinal lamina propria from groups of three piglets before, and 1, 2 and
      3 weeks after infection with virulent transmissible gastroenteritis virus (TGEV)
      at 2 weeks of age. The donor piglets developed clinical signs of transmissible
      gastroenteritis which persisted for up to 3 days, and they developed peak serum
      titres of TGEV-neutralizing antibodies 2 weeks post-infection. The leukocytes
      were cultured in the presence of pokeweed mitogen (PWM), various dilutions of
      purified TGEV, or control media for 3 or 5 days, and the culture supernatants
      were tested for antiviral activity in MDBK cells challenged with vesicular
      stomatitis virus. The antiviral activity was characterized as porcine interferon
      (IFN)-alpha or porcine IFN-tau on the basis of its stability at pH 2.0 and
      neutralization by anti-human IFN-alpha antibodies. Viability of the leukocytes in
      culture, determined by trypan blue exclusion, was highest for the peripheral
      blood leukocytes and lowest for the mesenteric lymph node leukocytes. There were
      no consistent differences in antiviral activity between cultures incubated for 3
      or 5 days. Porcine IFN-alpha was found in the supernatants of the leukocyte
      cultures stimulated with TGEV antigen, harvested before or after infection of the
      donor piglets with TGEV. Porcine IFN-tau was demonstrated in the supernatants of
      the leukocyte cultures stimulated with PWM, more frequently when the leukocytes
      were harvested post-infection. This was the first demonstration of IFN induction
      in vitro in leukocytes from porcine gut-associated lymphoid tissue.

PMID- 1345592
TI  - Observations on the conditions of work of Polish seafarers and their health.
AB  - Conditions of work of seafarers depend on the influence of physical, chemical
      biological and psycho-social factors. In 1971-1973, the health of 3000 sefarers
      was examined; their main health problems were: neuroses (10.13%), arterial
      hypertension (4.63%), ulcer of stomach and duodenum (2.80%), renal calculi
      (2.80%), and the alcoholic addiction (1.73%). Those seamen worked on cargo ships
      which technically differed from ships which sail the seas in the nineties; they
      were slower, to load them and unload took much time, and they stayed in ports for
      long periods of time. Recent technical developments in shipbuilding, and the
      trend to build larger ships with more powerful engines and greater cruising
      speed, the mechanization and automation of ships operation, and computerization,
      caused the change in their crews structure and number. It also changes the psycho
      social work environment. Using the same method, health examinations of 3,300
      seafarers were conducted in 1983-1985. There was an increase in the prevalence of
      neuroses, arterial hypertension, ulcer of stomach and duodenum, and calculus of
      kidney. In 1990-1992, a group of 4,688 seafarers was examined. Their health
      problems were different, in comparison with the populations previously examined.
      For example, neuroses were recorded in 1.16% men, and ulcer of stomach and
      duodenum in 0.13% of men examined. The above differences in the health status of
      seafarers examined cannot be attributed only to the changes in their work
      conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345593
TI  - Prevalence of HIV-antibodies in maritime workers and in other selected population
      groups in Poland.
AB  - The objective of the present work was to determine prevalence of HIV-antibodies
      in the following population groups: 1. Seamen, fishermen and dockers from region
      of Gdansk and Szczecin 2. Travellers abroad. 3. Special risk groups (intravenous
      drug users, prostitutes, homosexuals, haemophiliacs) mostly from Gdansk region.
      4. Hospital patients, prisoners, other people. Abbott recombinant HIV 1/HIV 2 EIA
      was used for the detection of antibodies to HIV type 1 and/or type 2. In the
      period from 1987 to 1992, 70,297 examinations were made. HIV-antibodies were
      detected in 165 people (0.23%). Out of 35,084 subjects in the first group (926
      women and 34,158 men). 20 men were found seropositive (0.06%). The majority of
      them--16 men were seamen, 3 were fishermen and one was a harbour worker. In the
      second group made of 27,403 people including 3,640 females, HIV-antibodies were
      revealed in 9 men (0.04%) and one woman. In the third group, there were 965
      people including 482 women; among them there were 104 men and 19 women infected
      (12.8%). Out of the 349 prostitutes examined 2 were infected (0.05%). Among 79
      homosexuals, 4 were found infected. In the sample of 14 haemophiliacs none
      demonstrated HIV-antibodies. In 6,845 subjects of the fourth group (5938 males
      and 907 females), 12 males were seropositive (0.18%). In that number 5 were
      prisoners, other 5 were hospital patients and 2 were known to have homosexual
      relationship with infected men. The majority of subjects with HIV-antibodies were
      men--145 (88%) of the total number of subjects infected, aged 20-40.

PMID- 1345594
TI  - Is there need for change of health examinations for sea pilots?
AB  - Sea pilots must be capable of carrying out their work in all situations. Thus,
      they must not have any disease or defect, that could impair their job
      performance. By periodic medical examinations attempts are made to ensure their
      working capacity. In most countries these examinations are carried out by a
      general practitioner and they include only few if any objective laboratory tests.
      The aim of the present investigation was to study the effectiveness of the
      periodic medical examinations to find out in the population of pilots examined
      persons with health risks, especially risks for cardiovascular diseases. All the
      pilots examined were over 45 years old (n = 135, response rate 88%). Self
      evaluation of health was carried out by a questionnaire. Blood analyses were made
      and chest X-ray as well as exercise-ECC were taken. The most common subjective
      symptoms concerned musculoskeletal and gastrointestinal systems; sleep
      disturbances were also quite common. The three most frequent diseases diagnosed
      earlier by a doctor were musculoskeletal and gastrointestinal diseases, and
      arterial hypertension. About 24% of pilots had a lower physical working capacity
      than predicted. The body mass index indicated at least 11% overweight in half of
      the cases. At exercise-ECG four pilots appeared to have an ischaemic heart
      disease and additionally eleven pilots had abnormal ECG. Over 80% of pilots had a
      serum cholesterol value higher than 5 mmol/l, and serum triglyceride values
      exceeded the normal value of 2.0 mmol/l in every fourth case. Serum glutamyl
      transaminase was pathological in over 20% of the cases, and serum glucose level
      in 8%. The findings by routine physical examinations were very few consisting of
      stiffness in musculoskeletal system, two cases of elevated blood pressure, two
      heart murmurs, varicose veins etc. In two cases an inguinal hernia was suspected.
      The current periodic health examinations does not seem to effectively prevent a
      person with possible health defect from working as a sea pilot. More objective
      tests must be included in these examinations and more attention should be paid to
      prevention of overweight, effective treatment of musculoskeletal symptoms,
      improving physical working capacity and helping pilots to manage their psychic
      stress.

PMID- 1345595
TI  - Work-related lost time accidents in deep-sea fishermen.
AB  - To evaluate the problem of work-related accidents and injuries in fishermen, a
      survey was conducted among crews of deep-sea fishing trawlers-factory ships of 3
      large fishing companies, covering the period of 10 years (1977-1986). In the
      surveyed population of 10,475 men and a control group of 4,073 workers employed
      on shore, there were altogether 1,688 work-related accidents recorded, including
      33 fatal accidents. Their incidence was 16.54 per 1000 per year (0.32 fatal cases
      per 1000 men per year). In the control group (n = 4,073 workers), the incidence
      was 27.98 per 1000 men (0.03 fatal accidents per 1000). There were more accidents
      recorded in the control group, than in fishermen. But the incidence of fatal
      cases was about 10 times higher among fishermen than among workers employed on
      shore. Among 33 fatal cases in fishermen, there were 12 cases of drowning, 6-
      injuries, 2--intoxications, 1--burn, and 12 cases sudden death at sea considered
      as "work-related accidents".

PMID- 1345596
TI  - Work-related accidents and injuries in Baltic fishermen.
AB  - Data on the incidence of work-related accidents and injuries in Baltic fishermen
      employed on medium-size and small fishing vessels were collected during 9 years,
      and were compared with this incidence in the control group of shore workers, and
      in a group of deep-sea fishermen surveyed previously. The non-fatal and fatal
      injuries in Baltic fishermen occurred much more frequently, than in deep-sea
      fishermen employed on large ocean-going trawlers-factory ships. This may be
      related to the difference in the conditions of work on various types of fishing
      vessels.

PMID- 1345597
TI  - 100 years Port Health Authority in Hamburg.

PMID- 1345598
TI  - Some mortality data for Grimsby "lumpers" and fishermen.
AB  - All death certificates supplied to Grimsby District Health Authority for the
      years 1967-1980 were examined. Certificates showing the occupation on fisherman
      (or similar term) or lumper were extracted. Brief analysis of the data on the age
      and cause of death stated on those certificates is presented. There was no
      indication that the mortality pattern differed significantly between the two
      groups or from that of the community from which the lumpers and fishermen came.

PMID- 1345599
TI  - Traumatism with fatal outcome in maritime workers.
AB  - 102 work-related injuries with fatal outcome among crews of ships of Northern
      Water Basin in Russia were analysed. The alcohol use and abuse was a major risk
      factor in accidents and fatal injuries in seafarers and fishermen. Medical and
      social aspects of the problem, and prevention measures were discussed.

PMID- 1345600
TI  - Assessment of phonocardiographical investigations among seafarers.
AB  - A total of 763 seafarers were selected at random for the examinations. Their
      number represented 9.82% of the total employed. About 86.63% of them were
      examined. Another group examined were 202 college undergraduates--all the
      undergraduates of the second year of studies. The average age of seafarers was
      41.14 +/- 8.84 years, and of undergraduates 22.54 +/- 1.29 years. A normal heart
      first sound was recorded in 95.41% of seafarers, normal second sound in 95.94%,
      and in 95.05% and 95.05% of the undergraduates, respectively. Normal third and
      fourth sounds were recorded jointly in 4.45% of seafarers and 0.99% of the
      undergraduates, whereas abnormal ones in 1.05% of seafarers and 0.99% of the
      undergraduates. Aortic ejection sound and systolic zone clicks were detected only
      in seafarers: in 0.79% and 1.31% of the subjects, respectively. Systolic zone
      murmurs were recorded in 4.19% of the seafarers, including those with heart
      defects (1.44%), therein mitral valve insufficiency (0.79%), mitral valve
      prolapse syndrome (0.39%) and aortal valve stenosis (0.26%). In all other cases
      the recorded heart murmurs in undergraduates and seafarers were considered
      functional (not pathological).

PMID- 1345601
TI  - Travellers diarrhea.

PMID- 1345602
TI  - Health care for nautical tourist.
AB  - Nautical tourism is one of the developing branches of tourism in Europe. It
      differs from other forms of tourism. Conditions under which nautical tourists
      live are similar to those of seamen employed on vessels in costal shipping. The
      health care for nautical tourists should be organized according to the principles
      of health care for crews of merchant ships engaged in constal shipping.

PMID- 1345603
TI  - Efficacy of hyperbaric oxygenation in atopic dermatitis.
AB  - Ten patients (5 with atopic dermatitis and 5 with asthma-prurigo) aged 8-38
      years, were treated with hyperbarie oxygenation, at the Institute of Maritime and
      Tropical Medicine. Daily one exposure was applied at 0.1 MPa pure oxygen, during
      15 days. Parallelly to the clinical evaluation also G, M, E immunoglobulins and
      the level of C3 and C4 complement were determined. All patients given this
      treatment improved clinically. In 9 of them, the level of IgE immunoglobulin
      decreased. The complement levels also decreased.

PMID- 1345604
TI  - [Gene therapy].

PMID- 1345605
TI  - [70-year old insulin].

PMID- 1345606
TI  - [Total joint arthroplasty].

PMID- 1345607
TI  - IARC monographs on the evaluation of carcinogenic risks to humans. Solar and
      ultraviolet radiation.

PMID- 1345609
TI  - Physician bonding.

PMID- 1345608
TI  - Digital signal processing system for real-time His-bundle and late potential
      measurement.

PMID- 1345610
TI  - Prevalence of depressive illness in general practice attenders.

PMID- 1345611
TI  - Unrecognized depression in general practice.

PMID- 1345612
TI  - Depressive thinking in general practice patients.

PMID- 1345613
TI  - Prevalence of depressive illness in the elderly community.

PMID- 1345614
TI  - Somatic presentation of depressive illness in primary care.

PMID- 1345615
TI  - Ruminal biohydrogenation of fatty acids from high-oleate sunflower seeds.
AB  - The objective of these experiments was to examine methods of modifying the fatty
      acid composition of bovine tissues. In the first experiment, four steers were
      fitted with duodenal fistulas and were assigned to four diets in a Latin square
      design. The steers were fed a control diet or the same diet containing 10% high
      oleate partially crushed sunflower seeds, serum-coated sunflower seeds, and heat
      treated, serum-coated sunflower seeds for 5 d. Samples of digesta and feces were
      collected on d 5. The inclusion of sunflower seeds (plain or serum-coated) in the
      diet increased (P less than .05) the digesta concentration of stearate. The
      percentage of stearate in the digesta and feces was increased (P less than .05)
      from 51 to 67% and from 64 to 74%, respectively, when steers were fed the
      untreated sunflower seed. The fecal concentration of oleate was increased (P less
      than .05) by dietary sunflower seeds in steers that were fed the serum-coated,
      unheated sunflower seeds. In a second experiment, heifers (four per group) were
      fed a corn-based control diet or diets containing 10% of high-oleate sunflower
      oil encapsulated with calcium alginate, either plain, coated with blood meal, or
      with blood meal integrated into the pellet. After 50 d on treatment, samples of
      perianal adipose tissue were obtained by biopsy. The fatty acid composition of
      the adipose tissue was not modified by the inclusion of the encapsulated oleate
      in the diet. In summary, limited ruminal bypass of sunflower seed oleate was
      accomplished with sunflower seed but not with encapsulated oleate.

PMID- 1345616
TI  - Toward an understanding of epithelial morphogenesis in health and disease.

PMID- 1345617
TI  - Dialysis and transplantation.

PMID- 1345618
TI  - Adequacy of long-term hemodialysis.
AB  - The gross mortality rates for end-stage renal disease patients treated with
      hemodialysis in the United States are twice those reported in Japan and Europe.
      This observation has prompted an inquiry into the methods used to administer
      dialysis therapy in these three areas of the world. It is apparent that shorter
      treatment time with multiple reuse of dialyzers was more frequently employed in
      the United States, and adequacy was more often judged by urea kinetic modeling,
      with the assumption that urea was a suitable surrogate for uremic toxicity. The
      possibility that inadequate therapy may result from too short dialysis time along
      with dialyzer reuse is suggested.

PMID- 1345619
TI  - Recent developments in peritoneal dialysis.
AB  - Significant developments over the past 10 years have established continuous
      ambulatory peritoneal dialysis as a successful kidney-replacement treatment.
      Peritonitis rates have fallen, and investigators are attempting to establish
      objective criteria for adequacy of dialysis. Malnutrition is a serious concern,
      but short-term experience with intraperitoneal amino acids promises success in
      the management of this complication. A significant improvement in the well-being
      of patients with end-stage renal disease was produced by recombinant human
      erythropoietin, and use of recombinant human growth hormone promises catch-up
      growth for children receiving long-term peritoneal dialysis treatment. As
      increasing numbers of patients are maintained on continuous ambulatory peritoneal
      dialysis over longer periods, we will begin to encounter beta 2-microglobulin
      related amyloidosis possibly at the same rate in these patients as in those
      receiving long-term hemodialysis treatment.

PMID- 1345620
TI  - Treatment of renal anemia with recombinant human erythropoietin.
AB  - It has been 6 years since the first reports of the use of recombinant human
      erythropoietin for the treatment of renal anemia appeared in the medical
      literature. During this period, erythropoietin has become established as a safe
      and highly effective therapy, and it is currently being evaluated for other
      nonrenal types of anemia. The initial clinical trials were in hemodialysis
      patients, followed by patients receiving continuous ambulatory peritoneal
      dialysis, and its use in predialysis and renal transplant patients is increasing.
      Various treatment schedules have been tried and compared; there are now reports
      of dosage frequencies varying from once daily to once weekly. Information has
      accumulated on the secondary effects of correction of renal anemia, particularly
      in relation to quality of life, exercise capacity, and cardiac function. Large
      multicenter trials have documented the safety profile of erythropoietin, whereas
      smaller studies have sought to elucidate the pathophysiology of its side effects,
      eg, hypertension and thrombotic events. This article reviews the latest
      developments in the use of erythropoietin in renal failure, concentrating
      particularly on those that have been published within the past year. Although
      there have been exciting advances in our understanding of the physiology and
      molecular biology of erythropoietin, these are amply described elsewhere and are
      beyond the scope of the present review.

PMID- 1345621
TI  - Factors affecting kidney transplantation success.
AB  - Forty percent of kidney transplants function for more than 10 years, allowing
      their recipients a lifestyle that is dialysis-free. Causes of success or failure
      of transplants are grouped into patient-related immunogenetic, pre- and
      perioperative, and postoperative factors. Some factors turn out to be
      interdependent, eg, the effect of pretransplantation transfusion and ethnic
      mismatch or donor age and ischemia; thus, no single analysis can be considered
      definitive. However, in documenting recent evidence gleaned predominantly from
      multifactorial analysis, we hope to assess relative risks associated with
      clinically important factors more accurately.

PMID- 1345622
TI  - Immunologic mechanisms of transplant rejection.
AB  - This article reviews recent progress in understanding the mechanisms of organ
      transplant rejection and focuses on studies that suggest new approaches to
      diagnosis and treatment. The alloimmune response is initiated by recognition of
      donor major histocompatibility complex antigens by the immune system of the host.
      During rejection, the upregulation of major histocompatibility complex antigens
      on donor tissue enhances this recognition phase. Rejection can be prevented by
      interfering with the interaction of recipient T cells with alloantigens using
      interventions such as antibodies against major histocompatibility complex
      proteins or accessory adhesion molecules, peptide-binding antagonists, and
      genetic alteration of major histocompatibility complex protein expression.
      Patterns of cytokines produced in the graft following transplantation may be used
      to distinguish rejection from other causes of transplant dysfunction. In
      addition, specific antagonists of individual cytokines show promise as
      antirejection treatments.

PMID- 1345623
TI  - Viral infection in the renal transplant recipient.
AB  - The viral infections with greatest impact on the renal transplant recipient are
      those due to cytomegalovirus, Epstein-Barr virus, and the two hepatitis viruses,
      hepatitis B and C. All of these are modulated by the administered
      immunosuppressive therapy, and all have both direct and indirect effects on the
      transplant patient. The direct effects are the infectious disease clinical
      syndromes that are produced (fever and malaise, pneumonia, hepatitis, and so
      forth). The indirect effects are several--all of these viruses contribute to the
      patient's net state of immunosuppression, predisposing him or her to the
      development of opportunistic superinfection with a variety of pathogens. In
      addition, both Epstein-Barr virus and hepatitis B virus have been clearly linked
      to the development of certain malignancies (lymphoproliferative disease and
      hepatocellular carcinoma, respectively). Finally, cytomegalovirus has been linked
      to allograft injury. Although antiviral strategies effective for cytomegalovirus
      and Epstein-Barr virus infection are being developed, similar programs are not
      yet available for the hepatitis viruses.

PMID- 1345624
TI  - Diagnostics and techniques.

PMID- 1345625
TI  - Clinical measurement of renal clearance.
AB  - The importance of renal clearance in uronephrology has motivated the continuous
      reassessment of well-established methods and the relentless search for better
      techniques. Concerning radionuclide methods, data in the current literature
      confirm the validity of the simplified one-compartment model or the empirical
      single-sample method for renal clearance measurement, and new algorithms have
      been described to broaden the application of the techniques to the pediatric
      population. Based on the same principles, accurate measurement of renal clearance
      can also be obtained using contrast agents. Using the technique for determination
      of the glomerular filtration rate during radiographic contrast examination is
      recommendable. However, potential adverse effects of the contrast substances
      should be compared with those of other methods before using this technique for
      measuring renal clearance without scheduled contrast roentgenographic
      examination. Controversy remains concerning the validity of predicting glomerular
      filtration rate from plasma creatinine. Although the predicted clearance is
      correlated with reference clearance, analysis of individual results reveals that
      important differences of up to 50 mL/min frequently occur.

PMID- 1345626
TI  - Radiographic techniques in renal parenchymal disease.
AB  - In his or her practice, the nephrologist usually has a substantial number of
      patients on dialysis for chronic renal failure. The longer a patient remains on
      either peritoneal dialysis or hemodialysis, the more at risk he or she is of
      developing acquired cystic disease of the kidney and renal cell carcinoma. Due to
      recent developments such as lower osmolar intravenous contrast media, sonography,
      and magnetic resonance imaging, the radiologist has the ability to assess the
      kidney in chronic renal failure with a growing number of less-invasive
      modalities. The lower osmolar agents appear to be less toxic to the kidney. Thus,
      they can be used when the benefit of the information obtained from a necessary
      procedure, eg, computed tomography or coronary arteriography, surpasses the risk.
      Duplex Doppler sonography can assess the pressure of flow in the arcuate vessels
      of the kidney with measurements of the resistive index. The resistive index is a
      proven tool for assessing rejection of the renal allograft--another newer
      application is in the diagnosis of obstruction. An elevated resistive index found
      in a kidney with a dilated collecting system confirms the diagnosis of
      obstruction. Studies are being made on its application in other renal disease
      processes as well.

PMID- 1345627
TI  - Uronephrologic nuclear medicine.
AB  - Nuclear medicine offers a rapid noninvasive means of evaluating suspected urinary
      tract disorders. Over the years, radionuclide scintigraphy has gained an
      important role in the evaluation of the renal transplant, possible obstruction,
      infection, and renovascular hypertension. During the past year, the importance of
      nuclear medicine within these areas has been confirmed. The diagnostic value of
      both diuresis and angiotensin-converting enzyme inhibitor renography is now
      generally accepted, whereas there is still disagreement about the optimal
      protocol. Renal scintigraphy is useful in patients with renal infection. Nuclear
      medical examinations have assumed a dominant role in the control and monitoring
      of renal transplants owing to their ability to quantify perfusion and function,
      but they do not obviate graft biopsy.

PMID- 1345628
TI  - Diagnosis of renal transplant rejection in the cyclosporine era.
AB  - The introduction in 1983 of cyclosporine as a prophylactic immunosuppressive
      agent has contributed to improved renal allograft survival at many transplant
      centers. However, in view of its profound nephrotoxic potential, the use of this
      drug in renal transplant patients has caused diagnostic confusion. An accurate
      assessment of whether the allograft dysfunction is from drug overdose or from
      acute rejection is important before one can manage the problem appropriately. The
      two practical measures that would help in distinguishing acute rejection from
      cyclosporine-induced toxicity are 1) a trial of cyclosporine dose-reduction and
      subsequent assessment of renal function, and 2) histologic assessment of the
      renal allograft biopsy specimen. In recent years, several new diagnostic
      techniques to assess the immunologic activity within the graft environment have
      been developed that could further enhance our discriminating ability. However,
      these sophisticated techniques are not readily available to most clinicians who
      are currently managing patients with graft dysfunction. This article focuses on
      the different methods of distinguishing rejection from cyclosporine-induced
      toxicity. The data were abstracted from relevant papers published in the
      scientific literature during the past 12 months.

PMID- 1345629
TI  - The insulin resistance syndrome.
AB  - Insulin resistance is a frequently occurring abnormality. Although there can be
      insensitivity to any of insulin's actions, insulin resistance par excellence is a
      decreased insulin-mediated whole-body glucose disposal rate. A distinction is
      made between primary and secondary insulin resistance. Primary insulin resistance
      is of unknown origin, is only partially experimentally reproducible, and is
      essentially irreversible (spontaneously or by treatment). In addition, it is both
      pathway-specific (ie, glucose storage) and organ-specific (mostly skeletal
      muscle), and is compatible with a postreceptor defect in insulin action. Primary
      insulin resistance is found in a proportion (approximately 25%) of otherwise
      healthy people, in non-insulin-dependent diabetes mellitus, essential
      hypertension, and some forms of dyslipidemia. The idea of an insulin resistance
      syndrome derives from the striking pattern of overlap among these clinical
      conditions. Their tendency to cluster in the same individuals is evident from
      both cross-sectional and longitudinal observations. It is proposed that the
      insulin resistance syndrome is a large constellation of interrelated changes in
      metabolic, anthropometric, and hemodynamic variables centered around insulin
      resistance or hyperinsulinemia. There is a significant genetic component, a
      predisposing influence for non-insulin-dependent diabetes mellitus, hypertension,
      dyslipidemia, and possibly, a distinct atherogenic potential.

PMID- 1345630
TI  - Assessment of autonomic nervous function in human hypertension.
AB  - In spite of the popular belief that "nervous tension," "stress," and hypertension
      are causally related, it has been difficult to prove a role of autonomic
      dysfunction in the genesis of essential hypertension. There are three major
      reasons for this: 1) autonomic function cannot be assessed with one simple test,
      2) the short-term "phasic" and long-term "tonic" autonomic control of blood
      pressure are not necessarily interrelated, and 3) hypertension is a dynamic
      process in the course of which there are changes in autonomic control. Some of
      the controversies in the field stem from the lack of appreciation of these
      limitations.

PMID- 1345631
TI  - Blood pressure measurement and monitoring.
AB  - Recent developments in blood pressure measurement have emphasized recordings
      taken outside the physician's office. Such readings can recognize the spuriously
      high levels recorded in "white coat" hypertension. Nocturnal and early morning
      readings can detect silent complications and impending cardiovascular accidents.

PMID- 1345633
TI  - Diagnostics and techniques.

PMID- 1345632
TI  - Dialysis and transplantation.

PMID- 1345634
TI  - Bioceramics in orthopaedic surgery: state of the art and preliminary results.
AB  - Ceramic materials utilized in orthopaedic surgery can be divided into bioinert,
      causing minimum tissue reaction, and bioactive types, capable of stimulating bone
      tissue growth, establishing a bond capable of supporting physiological loads.
      Alumina is a bioinert ceramic which shows excellent mechanical resistance and an
      extremely low level of wear when given appropriate structural characteristics. It
      is therefore used to make prosthetic hip components (head and acetabulum), to
      coat metal prosthetic shafts and to make prostheses for small joints. Among the
      bioactive ceramics, bioglass, bioglaze and hydroxylapatite are included in the
      study. At present, bioglass and bioglaze appear interesting, but not sufficiently
      so as to find a precise niche in orthopaedic surgery. Currently the bioactive
      ceramic with the most possibilities for use in orthopaedic surgery is
      hydroxylapatite. The close interfacial bond which is established with bone tissue
      allows it to be used as a filler for defective bones in various skeletal diseases
      and as a coating for metal prosthetic substrates.

PMID- 1345636
TI  - Cooper's technique in the treatment of neuromuscular pes cavovarus.
AB  - The authors present the technique described by Cooper to correct neuromuscular
      pes cavovarus and the results of 13 cases of pes cavovarus treated at the
      Orthopaedic Clinic of "La Sapienza" University in Rome. Cooper's technique seems
      to be a valid way of correcting pes cavovarus, particularly in growing patients
      or those with anterior deformities.

PMID- 1345635
TI  - Surgical treatment of Legg-Calve-Perthes disease.
AB  - Thirty-two patients (out of 52 undergoing surgery) with Legg-Calve-Perthes
      disease (LCP) were examined retrospectively to assess the efficacy of surgical
      treatment on epiphyseal morphology at the primary healing. The analysis of the
      clinical results of the 33 hips considered indicated that it is necessary to
      operate above all on 3rd grade hips. For these the most frequent operation
      indicated is osteotomy of the pelvis. Femoral osteotomy must be limited to cases
      with only a slightly deformed femoral epiphysis in patients below the age of 7-8
      years.

PMID- 1345637
TI  - Arthrolysis in the treatment of ankylosis and severe post traumatic stiffness of
      the elbow.
AB  - Between 1977 and 1989 the authors performed arthrolysis on 18 patients with
      ankylosis or severe post traumatic elbow stiffness. After an analysis of the
      cases, the operative technique is described and original parameters are proposed
      to evaluate the consequent results. The validity of arthrolysis as a possible
      alternative to arthroplasty or arthroprosthesis is confirmed by the 67% positive
      results.

PMID- 1345639
TI  - Elastic intramedullary ender nailing in fractures of the tibia: clinical
      statistical review.

PMID- 1345640
TI  - Percutaneous pinning of displaced supracondylar fractures of the humerus in
      children. Case report.
AB  - The authors report their experience with closed reduction and percutaneous
      pinning of twenty-two supracondylar fractures of the humerus in children. In
      cases with neurovascular complications there was a marked regression within six
      hours following reduction. The results after 15 months to 13 years were
      satisfactory (excellent + good) in 90% of the cases, avoiding the risks and
      possible cicatricial complications of incisions and the discomfort of orthopaedic
      treatment in traction and subsequent thoracic-brachial plaster cast.

PMID- 1345638
TI  - Allograft revision surgery of failed hip replacements: X-ray pattern and clinical
      results.
AB  - The authors describe their experience with allograft in 23 cases of revised hip
      replacements, paying particular attention to the clinical results and the X-ray
      appearance. They conclude by emphasizing the particularity of the surgical
      technique and the various factors involved in the use of bone grafts in such
      elective surgery as hip replacement.

PMID- 1345641
TI  - Thrombophlebitic complications in arthroscopic surgery of the knee.
AB  - Arthroscopic surgery is generally considered to be free of any significant
      complications. In particular, there is a much lower incidence of vascular
      complications as compared with open surgery of the knee. A careful examination of
      the literature, made by the authors, and an in-depth analysis of a significant
      sample (790 patients over 2 years) out of a total of more than 2200 knee
      arthroscopies performed over 7 years, has shown that thrombophlebitis is in fact
      an important complication especially in patients over the age of forty. The need
      for an accurate preliminary study to identify the patients at risk and for
      regular and specific out-patient check-ups to prevent the onset of severe
      vascular and thrombophlebitic complications is stressed.

PMID- 1345642
TI  - Measurement of extensor hallucis longus power in patients with hallux valgus. Is
      the Dandy sign reliable in cases of hallux valgus?
AB  - The authors took manual and dynamometric measurements of the power of the
      extensor hallucis longus (EHL) muscle in 100 patients with juvenile hallux valgus
      and 141 normal patients. Three degrees of valgus deformation were recognized:
      mild (15-25 degrees), moderate (26-35 degrees), and severe (> 35 degrees).
      Neither the manual nor the dynamometric measurements showed any difference in EHL
      power between the normal patients and those with mild valgus deformity. In the
      patients with moderate valgus deformity, the manual measurement usually showed
      the EHL force to be the same as that of the normal patients, while the
      dynamometric measurement gave a lower value. The patients with severe valgus
      deformation were shown to have a slight to moderate loss of power on manual
      measurement and a greater loss of power on dynamometric evaluation. Both methods
      of measurement are equally reliable. When the valgus deformation is mild to
      moderate, any loss of EHL power must be attributed to another cause; when the
      valgus deformation is severe, however, it by itself provokes a significant loss
      of EHL power. The Dandy maneuver is unreliable only in cases of severe hallux
      valgus.

PMID- 1345643
TI  - Functional evaluation of patients fitted with total knee prostheses.
AB  - Degenerative or inflammatory diseases of the knee joint account for a large
      proportion of diseases affecting the elderly. Treatment aims to eliminate pain,
      correct the deformity and maintain complete joint mobility. In cases of total
      joint degeneration, fitting of a joint prosthesis is the technique currently
      favoured since elimination of pain and correction of the deformity, accompanied
      by recovery of joint mobility (the fundamental requirements for normal everyday
      life) can only be obtained if the knee joint is completely replaced. With the
      discovery of new materials and increasingly sophisticated knowledge about
      articular mechanics, the knee prosthesis, although more recent than the hip
      prosthesis, has become ever more widespread to the point that it now represents
      an irreplaceable aid in the treatment of this common disease. The clinical
      results obtained are already stable and particularly encouraging and prosthesis
      design is sophisticated and accurate. There is, however, still the suspicion that
      current prostheses can be considered "rudimentary" in comparison with the
      physiological and biomechanical behaviour of the human joint. We therefore wanted
      to begin an evaluation using a gait analysis system to assess patients fitted
      with knee prostheses. The first impressions gained in this study are the subject
      of this article.

PMID- 1345644
TI  - Genu recurvatum following distal epiphysiodesis of the femur: X-ray evaluation
      and therapeutical approach.
AB  - Acquired genu recurvatum may have bone, capsulo-ligamentous or combined origins.
      It may affect the tibia or femur and various etiologies are possible. However,
      its pathogenesis is often linked to partial anterior epiphysiodesis following
      traumatic damage to the femoral or tibial growth plate. In this study we examine
      femoral recurvatum, a form which occurs only rarely. The clinical and
      radiographic characteristics are described in depth and the surgical indications
      for correction of this deformity are defined. Radiographic examination was used
      to complete the goniometry of the recurvatum deformity by calculating the dia
      intercondylar angle, measureable on lateral radiographs of the knee. The normal
      value is 33 degrees (+/- 3 degrees) while in the patients with femoral recurvatum
      it was noticeably higher. In cases of isolated femoral recurvatum we carried out
      a supra-condylar osteotomy with removal of a bone wedge aimed at normalizing the
      dia-intercondylar angle. In the cases treated at our Centre, the objective,
      subjective, functional and radiographic results were good, with a mean follow-up
      of 6 years. CLINICAL IMPORTANCE: as well as completing the goniometry of the
      recurvatum, the dia-intercondylar angle makes it possible to draw up a correct
      pre-operative plan, enabling precise surgical correction to be carried out.

PMID- 1345645
TI  - Staging of malignant tumours of the foot.
AB  - Tumours of the foot in general, and malignant tumours in particular, are
      extremely rare. In the absence of a large series it is necessary to resort to
      surgery based on "principles" and not on experience or on data drawn from
      retrospective clinical studies. Enneking's "Surgical Staging System" (S.S.S) is a
      method of staging musculo-skeletal tumours which has been universally adopted-for
      several years and which is based, as already known, on the concept of anatomo
      surgical "compartments". In the particular case of the foot, the S.S.S. suggests
      the surgical criteria specific to each anatomical region. The authors illustrate
      the principles with some examples taken from their experience, evaluating the
      surgical, oncological and functional aspects.

PMID- 1345646
TI  - Sciatic nerve palsy associated with total hip arthroplasty.
AB  - Six cases of clinically evident sciatic or peroneal nerve palsy occurred in a
      consecutive series of 380 total hip arthroplasties (THA). An additional eight
      cases of peroneal nerve palsy due to pressure from Thomas splint or tight
      bandages were seen. Factors apparently causing nerve palsy were significant
      lateralization and lengthening in four cases and dislocation of the hip in one
      case. The cases with neuroapraxia of the peroneal nerve were seen from the third
      to the fifth day of Thomas splint immobilization. EMG studies were conducted in
      all six group 1 patients; at the end of one year the results were good in two
      cases, fair in three cases, and poor in one case. The results suggest that limb
      lengthening should be limited to 4 cm to minimize this complication. It was also
      seen that patients with peroneal nerve palsy due to local compression do well,
      though some are bothered by mild residual dysesthesia over the dorsum of the
      foot. In contrast, patients with sciatic nerve palsy do not have such a good
      outlook.

PMID- 1345647
TI  - Morphological or functional criteria in evaluation of the newborn hip?
AB  - Classifying the infant hip as normal or dysplastic before the stage of
      radiological significance, in other words during the first three months of life,
      has always been trusted to functional maneuvers causing clinical signs. From the
      results it is possible to deduce if the hip morphology is normal or somehow
      altered. In other words, because insufficient radiographic significance makes it
      impossible to directly assess the "morphological" criterion, diagnosis of the
      state of the hip is carried out using an indirect "functional" criterion. In
      contrast to radiographic imaging, ultrasound screening is already significant in
      the first weeks of life; it is therefore now possible to obtain real images of
      the infant hip earlier than it was possible using radiography. This eliminates
      the need for symptomatic evidence of dislocation. As a result, the "functional"
      indirect criterion used up till now for early diagnosis of infant hip can today
      be replaced by a direct "morphological" criterion. This innovation is not without
      epidemiological consequences, and this must be taken into account in order to
      rationalise between the opposing risks of over or under estimating the incidence
      of congenital hip dysplasia.

PMID- 1345648
TI  - Synovial osteochondromatosis of the sole of the foot. A case report.
AB  - Synovial osteochondromatosis of the foot is a rare disorder. We present the first
      report of synovial osteochondromatosis of the intermetatarsal/tarsometatarsal
      joints. When a mass develops in the sole of the foot and heterotopic
      ossifications are revealed radiographically, synovial osteochondromatosis should
      be considered in the differential diagnosis.

PMID- 1345649
TI  - Reduction and osteosynthesis of subcapital fractures of the femoral neck:
      possible repercussions on post-fracture hemarthrosis of the hip.
AB  - Intracapsular hip pressure was measured in undisplace or less displaced
      subcapital fractures of the femoral neck before and after open reduction and
      internal fixation with three-flanged nails. After reduction and osteosynthesis,
      intracapsular pressure increased in three out of five cases. The result is
      discussed in relation to the possible role of intracapsular pressure sustained by
      hemarthrosis in the pathogenesis of post-traumatic vascularity of the femoral
      head.

PMID- 1345650
TI  - Bilateral aseptic necrosis of the humeral head following combined therapy for
      Hodgkin's lymphoma.
AB  - A young woman treated with combined therapy (chemo- and radiotherapy) for
      Hodgkin's disease later developed avascular necrosis of the humeral heads. The
      unusual location of the aseptic necrosis, and particularly the fact that it
      occurred bilaterally, made the case exceptional. The hypothesis is that the
      radiotherapy was a contributory factor.

PMID- 1345651
TI  - Kienbock's disease in an eleven-year-old girl. A case report.
AB  - Kienbock's disease occurs most frequently between 20 and 30 years of age
      (Gillespie, 1961). The youngest patient with Kienbock's disease in literature
      written in English is a 10-year-old boy (Nakamura et al., 1990). We report the
      case of an 11-year-old girl with Kienbock's disease whom we treated with radial
      shortening. Five months after surgery, radiographs showed signs of rapid
      disappearance of avascular necrosis of the lunate, and the patient had excellent
      clinical results. Two years postoperatively no recurrence of avascular necrosis
      of the lunate has occurred.

PMID- 1345652
TI  - A case of non-ossifying fibroma.
AB  - The authors describe a case of non-ossifying fibroma which, because of its
      particular clinical and radiographic features, had previously been diagnosed as
      osteoid osteoma. Taking this as the starting point, the relationship and the
      differential diagnosis between these two well-known disorders is discussed.

PMID- 1345653
TI  - A solitary metastasis of the patella.
AB  - A case is reported of a solitary metastasis of the patella from a "poorly
      differentiated adenocarcinoma", the first sign of the primitive tumour for a long
      time unidentified. The authors point out that this occurrence, although rare,
      should be considered in the differential diagnosis of knee pain.

PMID- 1345654
TI  - Osteolysis of the distal clavicle in a woman. Case report and review of the
      literature.
AB  - An unusual case of osteolysis of the distal clavicle in a woman is presented.
      Although almost 100 cases of osteolysis of the distal clavicle have been reported
      in the literature, none have occurred in females (Neer and Rockwood, 1984). After
      acute acromioclavicular dislocation, surgical reduction was carried out by
      transferring the coracoid process to the clavicle. Three years later the
      osteolysis of the outer clavicle appeared to be related to pain and functional
      impairment of the joint. The pain is quite tolerable and surgical excision of the
      distal clavicle has not yet been necessary.

PMID- 1345655
TI  - [Radiologic diagnosis of morphologic and functional changes in the
      bronchopulmonary system in workers employed in production and processing of
      ethylene oxide].
AB  - A total of 3475 subjects, engaged in such production for 2-20 years, were
      annually and before starting work examined by clinical and x-ray methods; 2427 of
      these were regularly exposed to ethylene oxide (the main group). X-Ray
      examinations included roentgenomorphologic (total fluorogram of the thoracic
      cavity organs and long-distance roentgenograms, tomograms, bronchograms, if
      necessary) and roentgenofunctional (roentgenopneumopolygraphy) methods of
      examination of the bronchopulmonary system. Chronic bronchitis was detected in
      407 workers of the main group and in 79 controls; in 76.2% of the main group
      patients and in 90% of controls it was chronic nonobstructive functionally
      unstable bronchitis, in the rest it was chronic obstructive bronchitis.

PMID- 1345656
TI  - [Computerized planning of radiotherapy].
AB  - The hypophysis was studied by MR tomography in 148 patients with the most
      prevalent diseases of the hypothalamohypophyseal system and in 13 ones with
      primary hypothyrosis. The findings evidence a great variety of changes in the MRT
      picture in the examinees. The method permits a reliable diagnosis of hypophyseal
      macroadenoma and of an 'empty' sella turcica. Qualitative and quantitative
      criteria for MRT diagnosis of these conditions are suggested. The diagnostic
      value of MRT for the detection of macroadenomas is still to be researched. The
      method was effectively used for a dynamic follow-up of the hypophyseal status in
      the course of pathogenetic therapy; the formation of an 'empty' sella turcica is
      possible against the background of dopamine agonist therapy and substitution
      therapy of primary hypothyrosis.

PMID- 1345657
TI  - [MRI and computerized tomography in the evaluation of lumbar spine after
      herniated disk surgery].
AB  - The authors analyze the results of comprehensive radio-diagnosis in 44 patients
      previously operated on for lumbar hernias. All the findings of magnetic resonance
      tomography and computer-aided tomography were divided into 3 groups: (1) natural
      consequences of a surgical intervention without clinical manifestations; (2)
      complications after a surgical intervention; (3) recurrent hernias or hernias on
      an adjacent level. The most intricate problem was the differential diagnosis
      between a recurrent hernia and a postoperative epidural cicatrix. Criteria to
      distinguish between these two conditions are suggested. The authors emphasize
      that the optimal variant for examination of the patients operated on is a
      combination of magnetic resonance tomography and computer-aided tomography.

PMID- 1345658
TI  - [Developmental defects of the facial the skull in some forms of
      craniosynostosis].
AB  - Changes in the facial skull of 74 patients with untimely synostosis of
      craniocerebral sutures and pathologic shape of the cerebral skull are
      characterized. All the patients presented with shortened base of the skull, gross
      deformations of the facial skull. Certain regularities in the formation of these
      defects were distinguished.

PMID- 1345659
TI  - [Radiologic densitometry in the evaluation of disorders of bone mineral density
      in patients with diabetes mellitus].
AB  - Presents a quantitative assessment of the total content of minerals in bones of
      50 diabetics and 50 controls, carried out by a modified photodensitometric
      procedure. The data evidence a significant reduction of the mineral content in
      the bones of diabetes mellitus patients, this permitting an earlier detection of
      osteoporosis in the course of diabetes.

PMID- 1345661
TI  - [Role of radiologic diagnosis in the evaluation of morphologic and functional
      changes in muscular veins of the leg in the pathogenesis of varicose disease].
AB  - A total of 100 patients with varicosis of lower limb veins were investigated with
      the help of distal ascending phlebography in horizontal, vertical and tilted
      positions. Considerable differences in x-ray images of musculi gastrocnemius and
      soleus (MGS) were noted. Four main types of MGS (conic, spindle-form, U-form, and
      balloon-like) were singled out. Correlation between muscular vein sizes and
      stages of varicosis was revealed. An important role of the pathology of muscular
      veins in dysfunction of the leg pump as one of the factors of pathogenesis of
      lower limb varicosis was confirmed.

PMID- 1345660
TI  - [Tolerance to standard and non-ionic contrast media in patients with ischemic
      heart disease and stable angina pectoris during coronary angiography].
AB  - Angiography of the coronary arteries with iohexol was carried out in 45 coronary
      patients with stable angina pectoris and that with diatrizoate in another group
      of 45 similar patients. Iohexol was tolerated better that diatrizoate.
      Physiological and hemodynamic side effects of iohexol were less marked than those
      of diatrizoate.

PMID- 1345662
TI  - [Linear parameters and types of thyroid structure in normal subjects of both
      sexes and various ages in ultrasonic imaging].

PMID- 1345663
TI  - [Diagnostic perspectives of mobile radiographic computerized tomography].
AB  - The authors assess mobile methods of x-ray computer-aided tomography (CAT) and
      suggest an organization and methodological scheme of its application. Their
      program of the first and up to now the only one in this country mobile CAT device
      is based on the new principles of mobile CAT application. It is realized in
      special hospitals of large regions, where the patients with the optimal
      indications for CAT are assembled. Over 15,000 examinations were carried out with
      the use of the suggested CAT program over 4 years, that resulted in detection of
      1295 brain tumors, 804 cases with neoplastic involvement of the abdominal cavity
      and the retroperitoneal space. The authors claim that wide application of mobile
      CAT devices according to the program they suggest will help decide the problem of
      unavailability of such examinations, for it will rule out the principal cause of
      this unavailability--economic problems arising because of high price of this
      equipment. One mobile device may replace 3 permanent CAT devices, if used
      according to the program suggested by the authors.

PMID- 1345665
TI  - [training of radiologic surgeons].

PMID- 1345664
TI  - [Nuclear magnetic tomography in the diagnosis of spinal cord cysts].
AB  - Magnetic resonance tomography (MRT) was used in examinations of 172 patients with
      spinal cord abnormalities. Thirty-eight cysts were detected: 25 in syringomyelia,
      5 in intramedullary tumors, 4 posttraumatic and 4 postoperational ones. Based on
      the MRT patterns, two types of syringomyelia were distinguished, the occlusive
      and idiopathic ones. The size and site of cyst, as shown by the MRT, did not
      conform to its neurologic symptoms. A characteristic feature of tumorous cysts
      was a highly intensive signal originating from their contents. Traumatic cysts
      were detected against the background of diffuse atrophy of the cord. Computer
      aided tomography did not give full-value information in such cases and therefore
      could not be recommended in cases with suspected intramedullary cysts.

PMID- 1345666
TI  - [Use of the radiographic contrast agent "Micropack N.D."].

PMID- 1345667
TI  - [A case of splenic lymphosarcoma].

PMID- 1345668
TI  - [A case of hereditary familial osteopoikilosis].

PMID- 1345669
TI  - [Diagnosis of the obstructed pulmonary abscesses].
AB  - Only spot bronchography, and if its results are negative, transthoracal puncture
      permit a correct diagnosis of blocked or partially blocked pulmonary abscess in
      2/3 of cases. This result is of importance for the choice of the treatment
      strategy in such patients. Use of thin or super-thin needles for puncture helped
      to do without serious complications and obtain reliable diagnostic information in
      90% of cases.

PMID- 1345670
TI  - Brief report: a double-blind study of naltrexone in infantile autism.

PMID- 1345671
TI  - Novel roles for neurotrophins are suggested by BDNF and NT-3 mRNA expression in
      developing neurons.
AB  - The results of our in situ hybridization experiments demonstrate that sensory
      neurons, sympathetic neurons, and motoneurons express brain-derived neurotrophic
      factor and/or neurotrophin-3 mRNAs during development in mouse. In accordance
      with previous data, we also find neurotrophins in the targets of sensory neurons
      (skin) and motoneurons (muscle) and the neurotrophin receptors p75, trkA, and
      trkB in sensory and sympathetic ganglia. These results suggest that neurotrophins
      have roles other than being target-derived factors that support neuron survival
      during developmental cell death (neurotrophic hypothesis), but may be transported
      in an orthograde fashion in neurons and released from axon terminals. We discuss
      several novel roles for neurotrophins, including autocrine/paracrine regulation
      of neuron survival, regulation of Schwann cell activity, and neuron to target
      signaling.

PMID- 1345672
TI  - [Effect of A, E, C, P vitamin complex on erythrocyte hemocoagulation properties
      and platelet aggregation in thrombinemia].
AB  - The protective effect of A, E, C, P vitamin complex has been experimentally
      proven to display in a decrease of animal death rate and in limiting the
      intensity of hemocoagulation shifts in thrombinemia. This effect is stipulated by
      a decrease in thrombocyte aggregation and in coagulation activity and by the
      increase of erythrocyte deformation properties. These changes seem to be caused
      by the effect of vitamins on the phospholipid spectrum, electrolyte transport of
      ATPases and erythrocyte membrane stability.

PMID- 1345673
TI  - A history of significant steroid discoveries and developments originating at the
      Schering Corporation (USA) since 1948.
AB  - A firsthand historical account of some of the significant contributions of the
      steroid research group at the Schering Corporation (Bloomfield, NJ, USA) to the
      discovery and/or development of important therapeutic agents is presented. These
      include the discovery of the antiinflammatory corticosteroid drugs prednisone,
      prednisolone, and betamethasone, all of which, more than 30 years after their
      introduction, continue to enjoy wide use in human and animal medical practice
      throughout the world.

PMID- 1345674
TI  - To purge or not to purge is not the question.

PMID- 1345675
TI  - Recovery of mononuclear cell subsets after bone marrow transplantation:
      overabundance of CD4+CD8+ dual-positive T cells reminiscent of ontogeny.
AB  - Patients after bone marrow transplantation are immunodeficient for months to
      years. To understand better the pathogenesis of this immunodeficiency, we studied
      quantitative reconstitution of blood monocytes, natural killer (NK) cells, T
      cells, and B cells at 2-22 months post-transplant. The results indicate monocyte
      and NK counts generally recover within 2 months, followed by CD4-CD8+ T cell, B
      cell, and finally (after > 1 year) CD4+CD8- T cell numbers. Dual-positive
      CD4+CD8+ T cells (which were barely detectable in normal adults), CD4-CD8+ T
      cells and B cells transiently reached supranormal levels during recovery. Both
      CD4+CD8- and CD4-CD8+ T cells were larger than controls throughout the 2-year
      follow up. Comparison with neonatal and infant mononuclear cell subsets suggested
      the reconstitution of CD4+CD8+ T cells and B cells is similar to ontogeny. In
      contrast, the reconstitution of CD4+CD8- T cells did not resemble ontogeny.

PMID- 1345676
TI  - Purging with 4-hydroperoxycyclophosphamide.
AB  - Over the past 10 years, very-high-dose cytotoxic therapy with rescue of marrow
      function by autologous bone marrow transplantation (BMT) has been shown to be
      effective treatment for patients with lymphomas and acute leukemias. However, a
      major concern has been that infusion of occult tumor cells with the autologous
      marrow will contribute to relapse. Accordingly, multiple techniques for treating
      autologous marrow grafts in vitro, to remove or "purge" occult tumor, have been
      developed. Despite controversy regarding the necessity and efficacy of purging,
      most autologous transplants for acute leukemia and many for lymphoma are
      currently purged. Most studies have used immunologic or cytotoxic agents for
      purging. The most widely used cytotoxic purging agents have been the
      cyclophosphamide congeners, 4-hydroperoxycyclophosphamide (4-HC) and mafosfamide.
      Since the first 4-HC-purged autologous marrow transplant was performed in 1980,
      over 700 patients have received 4-HC-purged autologous bone marrow transplants at
      Johns Hopkins alone. This review will chronicle the development of 4-HC as a
      purging agent.

PMID- 1345677
TI  - Use of the Terumo SteriCell for the processing of bone marrow and peripheral
      blood stem cells.
AB  - The SteriCell cell processing instrument is a good choice for a stem cell
      processing laboratory that is of sufficient size that they cannot share an
      apheresis machine with the blood bank. It is a laboratory instrument, with no
      facility for patient connection. Because of its minimal size and weight, it is
      easily stored in a cramped laboratory. Its automated programs are appropriate for
      processing of bone marrow and peripheral blood stem cells, and it is quite easy
      to learn how to use (in our laboratory, most individuals have been completely
      facile with the SteriCell after fewer than six processings). Based on reported
      results from other instruments, the SteriCell provides cell yields that are
      comparable to competing instruments. Service (provided by Haemonetics) has been
      satisfactory, and support from Terumo has been excellent. We can recommend this
      instrument to any other laboratory.

PMID- 1345678
TI  - Use of the polymerase chain reaction for the detection of tumor cell involvement
      of bone marrow and peripheral blood: implications for purging.
AB  - Bone marrow purging is being performed increasingly in an effort to deplete
      residual tumor cells from the graft prior to reinfusion. Several studies have
      suggested that the removal of tumor cells is an important clinical goal. In this
      review the utility of the polymerase chain reaction (PCR) for the detection of
      small numbers of tumor cells in bone marrow and peripheral blood is discussed.
      Using sensitive assays such as PCR, it is expected that the efficacy of bone
      marrow purging strategies will be improved and this will hopefully result in
      decreased relapse rates following autologous bone marrow transplantation.

PMID- 1345679
TI  - Oncogenes, molecular medicine, and bone marrow transplantation.
AB  - Retroviruses are known to carry specific genes that are likely to be responsible
      for induction of the malignant phenotype in the cells they infect. These genes,
      termed viral oncogenes (v-onc), have subsequently been shown to be derived from
      highly conserved, normal cellular genes commonly referred to as proto-oncogenes
      (c-onc). Proto-oncogenes are thought to be intimately involved in the processes
      of cell proliferation and differentiation. Therefore, any c-onc amplification,
      mutation, structural alteration, or change in transcriptional regulation might
      lead to, or be associated with, induction of a malignant phenotype. Targeted
      disruption of these genes may therefore be of therapeutic value. We discuss the
      role of antisense DNA in carrying out such therapy.

PMID- 1345680
TI  - Design of large-scale separation systems for positive and negative immunomagnetic
      selection of cells using superparamagnetic microspheres.
AB  - The ex vivo selective separation of cells from bone marrow and peripheral blood
      stem cell preparations is increasingly used as an adjunct to hematopoietic rescue
      following high-dose therapy for refractory cancer. Immunomagnetic separation, in
      which the target cells are identified using monoclonal antibodies and separated
      by attachment to paramagnetic particles and passage through a magnetic field, is
      widely used for both negative and positive cell selection. In this paper, we
      discuss the factors that should be considered when developing a magnetic
      separation device for purging tumor cells and selecting stem cells from bone
      marrow using superparamagnetic microspheres.

PMID- 1345681
TI  - The role of GAP-43 in the molecular regulation of axon outgrowth and electrical
      excitability.

PMID- 1345682
TI  - Multiple elements may be used for regulation of the GAP-43 gene in different cell
      types.
AB  - Recent evidence suggests that GAP-43 expression is not restricted to the nervous
      system, but may also occur outside the neural cell lineage. Two distinct patterns
      of GAP-43 regulation can therefore be distinguished. The first is the regulation
      of GAP-43 expression in multiple cell-types, and the second is the gene's
      temporal modulation within one specific cell-type. The latter type is well
      documented for neurons, where GAP-43 regulation is regulated in a fashion that is
      dependent on axon integrity. Results from partial analysis of the GAP-43
      promoter/enhancer region indicate that at least some of these aspects of GAP-43
      gene regulation may be accounted for by distinct cis-acting elements. For
      example, the expression of a rat GAP-43 promoter fusion gene in epidermal cells
      of transgenic zebrafish is dependent on an enhancer element, that is clearly
      distinct from the minimal neural-specific promoter. Characterization of specific
      GAP-43 regulatory elements responsible for particular aspects of its regulation
      may provide insight to signal pathways also utilized by other genes during
      development. Ultimately, a better understanding of the molecular events during
      development could help to define more precisely the complex sequences necessary
      for the establishment of an intact organism.

PMID- 1345683
TI  - Functional domains of neuromodulin (GAP-43).
AB  - Although neuromodulin (GAP-43, B50, F1, pp46, protein 4) was first identified
      over a decade ago, the physiological function(s) of the protein and the molecular
      mechanism(s) for its biological activities are still an area of active
      investigation. Neuromodulin has been implicated in several biological processes
      in neurons, including growth and regeneration, synaptic plasticity and
      neurotransmitter release. The molecular mechanisms underlying these implied
      physiological roles have not been elucidated, but there are several molecular
      properties of neuromodulin that may be important for its function in neurons. In
      this review, we will discuss research which has defined several of the functional
      domains of neuromodulin, including its phosphorylation sites, calmodulin binding
      domain, membrane binding domain and growth cone targeting domain. We will also
      suggest possible molecular functions of neuromodulin based on its biochemical
      properties.

PMID- 1345684
TI  - GAP-43 expression in macroglial cells: potential functional significance.
AB  - Although growth-associated protein-43 (GAP-43) was initially considered to be
      neuron-specific, it has more recently been found in astrocytes, oligodendrocytes,
      Schwann cells, glial cell equivalents in embryonic Drosophila and other non
      neuronal cells. Here I summarize evidence for the presence of GAP-43 in
      macroglial cells (i.e., astrocytes and oligodendrocytes) cultured from neonatal
      rat cortex and describe its developmental expression in a lineage-specific and
      cell-type-specific manner. These and other data suggest that GAP-43 is a
      multifunctional protein involved in the synthesis of membranes associated with
      the growth of various types of cellular processes, including those of macroglial
      cells.

PMID- 1345685
TI  - Schwann cells, neurons and GAP-43.

PMID- 1345686
TI  - GAP-43 in non-neuronal cells of the embryonic chick limb: clues to function.
AB  - The expression of GAP-43 in developing and regenerating neurons has been well
      characterized, but the function of this membrane-bound phosphoprotein is still
      unclear. Although GAP-43 is considered to be neuron-specific, it is also
      expressed in various glial cells of the peripheral and central nervous systems
      and in at least two populations of mesenchymal cells in the developing chick
      limb. GAP-43 mRNA is expressed transiently in developing limbs, which contain
      axons of spinal cord and dorsal root ganglion neurons, but do not contain
      neuronal cell bodies. This expression is correlated temporally with the in-growth
      of neurites and axons to the limbs, but appears to be independent of nerves. In
      some regions of the limb, GAP-43 immunoreactivity co-localizes in cells that are
      also immunoreactive for meromyosin, a muscle-specific marker. In addition, GAP-43
      mRNA and protein are particularly abundant in the interdigital mesenchyme that
      undergoes apoptosis, or programmed cell death. GAP-43 has been postulated to
      mediate rapid changes in cell shape and the extension of processes in neuronal
      growth cones and elongating axons. We suggest here that GAP-43 may serve a
      similar function in glial cells, in myoblasts fusing to form myotubes, and in
      apoptotic and phagocytic cells of the interdigital mesenchyme.

PMID- 1345687
TI  - [Jean-Louis Lortat-Jacob (1908-1992)].

PMID- 1345688
TI  - [Laparoscope and hernia surgery].
AB  - Attempts are now progressing to improve laparoscopic hernia surgery, which need
      our interest and reflexion. Widely informed on these new techniques, though not
      directly dealing with them, the author proposes, here, his own remarks.

PMID- 1345689
TI  - [Distal arterial bypass surgery for lower limb salvage].
AB  - From 1988 to 1990, 34 operations for distal arterial revascularization aimed at
      lower limb salvage were carried out in 29 patients with arteritis lesions at
      stage IV with distal necrosis (52%), severe stage III arteritis (10%), severe
      acute or subacute ischemia (38%). The indications and therapeutic modalities are
      described and discussed. The results are compared with the data found in the
      literature. This is an availability and emergency surgery, the last means to
      avoid life-saving amputation. The rate of patent revascularization after one year
      can be as high as 85 to 90%. Almost 9 extremities out of 10 can be saved.

PMID- 1345690
TI  - [Osteosynthesis using resorbable plates in maxillofacial surgery: hopes and
      disappointments].
AB  - The use of absorbable osteosynthesis material has two advantages in maxillofacial
      surgery: suppressing the possible biological effects of implanted metallic
      foreign bodies, making second surgery for material removal useless. Although the
      biotolerance of currently used materials is well known, the authors intended to
      test their use in the specific conditions of maxillofacial surgery, in which
      simply extrapolating the data collected in general surgery leads to erroneous
      conclusion. The authors report the results of a preliminary clinical study on 21
      cases of osteosynthesis of the upper third of the face using absorbable plates
      (18 fractures of the zygomatic bone, 3 maxillary osteotomies). The biotolerance
      of the material is very good, after more than 3 years for the oldest cases. The
      mechanical stability of the assembly is sufficient for the selected indications.
      As regards disappointments, these include the thickness of the plates, the
      difficulty to adapt them to bony surfaces, the fragility of the screws and the
      slow resorption of the material.

PMID- 1345691
TI  - [Immunotherapy of severe infectious states].
AB  - Although symptomatic treatments have been optimized, mortality in severe
      infectious conditions still exceeds 50% in many instances. Excessive activation
      of inflammation mediators, the endogenous relay of the initial stimulus, may
      account for the secondary occurrence of polyvisceral failure. This "internal"
      conception of severe infectious conditions opens new therapeutic possibilities
      including the modulation of the host's response. However, this new treatment of
      severe septic conditions, which complements antibiotic therapy and symptomatic
      measures, encounters several difficulties: a) proinflammatory mediators also have
      beneficial effects; b) as the mediator cascade is activated within a few hours,
      ordering immunity-modulating treatments early appears to be a logical step; c)
      monoclonal antibodies and recombining molecules are very expensive. Costs may be
      further increased by the probable need to use "cocktails" of antiinflammatory
      molecules. All these reservations show how technically blameless future clinical
      trials have to be. Cost efficiency and cost/benefit studies are also required. We
      may wonder whether society will make the financial choice to use these new
      treatments.

PMID- 1345692
TI  - [Gangrene of the perineum. Plea for a standardized therapeutic management apropos
      of 50 cases].
AB  - From 1988 to 1992, 50 cases of perineal gangrene were treated with a therapeutic
      protocol combining: a) repeated extensive excisions, b) hyperbaric oxygen
      therapy, even before surgery if this was possible, and c) intensive care. The
      mortality rate was 24% (12/50). It was even higher in patients admitted more than
      6 hours after diagnosis. The average stay in hospital was of 20 (+/- 2) days.
      Four patients presented with residual signs. Twenty-eight (56%) had had colostomy
      for lesions originating in the rectum or threatening the anal margin; 9 of these
      patients died, while gastrointestinal continuity was restored in another 17
      cases. There were three predictive factors of survival in this series: a) early
      diagnosis and treatment, b) severity index on admission, c) some associations of
      bacteria.

PMID- 1345693
TI  - [Role of hyperbaric oxygenation in the treatment of acute anaerobic infections].
AB  - Hyperbaric oxygenation (HBO), as an adjuvant treatment in necrotizing soft
      tissues infections and in gas gangrene is reviewed, including its specific
      effects, experimental studies and clinical reports. With a global therapeutic
      management, considered as an emergency state, including surgery, antibiotic
      regimens and HBO, we can obtained 50% mortality and morbidity decrease with a
      more conservative surgery. Finally, favorable outcome is associated with early
      therapeutics and localization of the initial necrotizing infection.

PMID- 1345694
TI  - [Relation between oxygen delivery and consumption during septic states. Value of
      an early dobutamine test].
AB  - From previous studies it has been hypothesized that multiple organ failure and
      high level of mortality, seen in critically ill septic patients, may be due to
      defective oxygen extraction and tissue hypoxia occurring early in the course of
      sepsis. Oxygen flux test has been proposed as a method of revealing an occult
      oxygen debt. We used a one hour dobutamine infusion test, in septic patients,
      without increase in blood lactate. Fifty patients with sepsis syndrome entered a
      multicentric prospective study. After fluid loading to increase pulmonary artery
      occlusion pressure (Paop) to a minimum value of 10 mmHg, all the patients were
      given 10 mcg/kg.min of dobutamine for one hour. Hemodynamic and metabolic
      variables were recorded before, HO, and after the test, H1 (cardiac index, Paop,
      oxygen deliver, DO2, and consumption, VO2, oxygen extraction ratio, (OER), blood
      lactate). The dobutamine test allowed to identify responders (R) who increased
      VO2 by more than 15% and non-responders. R and NR differed significantly in
      mortality (8.5% vs 44.4%). The test has a good predictive value for surviving.
      Without respect of the result of the test, the patients were randomized in two
      groups. The group D+ was given conventional therapy and dobutamine at the same
      rate of infusion for 9 consecutive days and the D- group received only
      conventional therapy. The RD+ patients improved more rapidly when compared with
      RD-, NRD+, NRD-. We concluded that a one hour dobutamine test is able to identify
      R and NR critically ill septic patients. The response is associated with
      significant difference in outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345695
TI  - [Perioperative parenteral nutrition. For whom? How?].
AB  - Preoperative artificial feeding (for 7 to 15 days) through an enteral or
      parenteral route is justified only in a subgroup of patients suffering form
      severe denutrition, who are scheduled for surgery with high morbidity or
      mortality. Postoperatively, the field of indication is broader, and it includes
      any patients who cannot soon feed themselves enough to catch their resting energy
      expenditure plus 20%. The administration route should use the technique with the
      lowest morbidity (enteral feeding) and the lowest costs. The role of new
      substrates (structured lipids, glutamine, trace elements) on immunity should be
      specified.

PMID- 1345696
TI  - [Post-stress acute hemorrhagic ulcers of the cecum. Apropos of 3 cases].
AB  - Three cases of acute ulcers of the cecum causing massive bleeding with
      hemodynamic impact are reported. These three cases involve young subjects (28, 31
      and 51 years old). Bleeding occurs after an aggression (post-traumatic context in
      2 cases, postoperative in 1 case). For these three patients, the angiographic
      location of arterial bleeding allows elective colic exeresis without rebleeding.
      From a pathogenetic point of view, the most likely hypothesis seems to be that of
      ischemic lesions following an aggression.

PMID- 1345697
TI  - [Free myocutaneous flap of the latissimus dorsi in cervicofacial surgery].
AB  - Free myocutaneous latissimus dorsi transplants are exceptionally used in
      cervicofacial surgery. The authors have performed an anatomical study of 23 non
      embalmed subjects, using injections of neoprene latex and barium sulfate into the
      axillary artery and dye injections. Dissections, arteriographs and corrosion show
      that the lower scapular pedicle is constant, with an average length of 9.5 cm and
      a caliber that is sufficient for vasuclar microsurgery. Eight patients with large
      T4 cervicocephalic neoplasms were operated, including two with tongue tumors, one
      with a tumor of the oropharynx, two oromandibular lesions, two lesions of the
      maxillary sinus and a neuroblastoma involving the middle level of the facial
      structures. A free myocutaneous latissimus dorsi transplant was used. The
      transplant was revascularised by neck vessels using microsurgical techniques.
      Complete success was obtained in all eight patients. Good functional, cosmetic
      and morphological results were obtained as a rule. In cervicofacial surgery, the
      authors have thus chosen and used a free myocutaneous latissimus dorsi transplant
      in three topographic indications: for the oropharynx, to fill large cavities,
      especially the maxillary sinus, and to fill the middle level of the facial
      structures and of the base of the skull.

PMID- 1345698
TI  - [Treatment of spontaneous pneumothorax under videosurgery, 32 cases (with
      videofilm presentation)].
AB  - From September, 1991, to June, 1992, 32 cases of pneumothorax were operated with
      thoracoscopy (video surgery). The indication was established for second
      recurrence in 6 cases, first recurrence in 14 cases, a persistent bulla or a lung
      failing to return to the wall after a first pneumothorax in 5 cases, and in the
      presence of a large pulmonary bulla on radiographs or CT scans during an initial
      episode in the last 7 cases. Thoracic CT was performed in 18 cases and
      demonstrated a system of bullae in 14 (13 in the apical segment and 1 in the
      segmentum apicale). The procedure included exeresis of the bullae on endo-GIA
      with apical and posterolateral parietal pleurectomy. In two cases, conversion
      into axillary thoracotomy was required because of extensive pleural adhesion in
      one case and of a technical problem in the other. The average duration of surgery
      was 72 mn. The thoracic drains were removed on the 2nd and 3rd postoperative
      days. Partial pleural detachment occurred in two cases, one on the 4th day and
      the other on the 5th day after surgery, with spontaneous return to the wall on
      the 8th day in both cases. The average stay in hospital was of 6 days. All
      patients were examined 15 days after discharge with a control radiograph, which
      was normal in all cases. No patient complained of parietal pain when no
      conversion into thoracotomy was made.

PMID- 1345699
TI  - [Role of herpes virus simplex and cytomegalovirus as cofactors of papillomavirus
      in dysplastic and cancerous lesions of the uterine cervix].
AB  - Human papillomaviruses (HPV) play an important role in cervical carcinogenesis
      but are probably not the only factors. To assess the role of HPV 6 and 11, of
      herpes simplex virus (HSV) and of cytomegalovirus (CMV) as cofactors for HPV 16
      and HPV 18, we used polymerase chain reaction (PCR). The genomes of these six
      viruses was searched for in cervical biopsies, inbred in paraffin, from 22 normal
      cervices, 21 low grade cervical intraepithelial neoplasia (CIN), 21 high grade
      CIN and 20 squamous cancers. HPV 16 DNA had the highest prevalence in cervical
      lesions. Its frequency reached 24% in low grade CIN, 57% in high grade CIN, 50%
      in cancers and 9% in normal cervices. The simultaneous presence of HPV 16 and/or
      HPV 18 DNA and CMV and/or HSV DNA was significantly more frequent in high grade
      CIN and cancers than in normal cervices. On the other hand the presence of HPV 16
      and/or HPV 18 DNA in samples lacking the other viral genomes did not
      significantly differ between the groups. Consequently the disease-viral infection
      relation was not apparent when these two "potentially oncogenic" HPV are isolated
      without coinfection by HSV or CMV. Our results are in agreement with the
      hypothesis of the role of herpesviruses as cofactors in cervical carcinogenesis.
      These viruses may disturb the control mechanisms of cellular growth and
      differentiation in HPV infected cells.

PMID- 1345700
TI  - [Reduction of atherogenesis in an arterialized venous graft by using an external
      sleeve].
AB  - The parietal thickening of a vein under hemodynamical conditions in the arterial
      system can be reduced when supporting the vein with a rigid external sleeve. To
      assess the role of thickness reduction in atherogenesis of an arterialized vein
      graft, a 4 mm thick external sleeve was implemented around the proximal half of a
      carotid-carotid vein graft in 16 New Zealand rabbits. Eleven rabbits were
      submitted to a hypercholesterolemic diet (HC group), while five others were
      submitted to a normal cholesterol diet (NC group). After eight weeks, a
      statistically significant difference in thickness was observed between free and
      sleeved segments, in the NC group with 105 +/- 9 microns versus 65 +/- 6 microns
      (p < 10.0001) respectively as well as in the HC group with 180 +/- 37 microns
      versus 99 +/- 35 microns (p < 10.0001) respectively. Studying the extent of
      soudanophilic lesions showed a statistically significant difference according to
      the use or not of an external sleeve where average extent is 68 +/- 17% in free
      segments versus 31 +/- 26% (p < 10.0001) is sleeved segments. The reduction in
      vein overfullness using an external constrictive sleeve prevents structural
      parietal changes in the vein and allows reducing atherogenesis of the
      arterialized vein graft.

PMID- 1345701
TI  - [Cyclosporin A metabolism and induction of cytochrome P-450 in orthoptic hepatic
      transplantation in rats].
AB  - The aim of our study were 1) to establish that cyclosporin (CsA) metabolism was
      correlated with the rate of cytochrome P4503A (cyt.) in Wistar rats induced with
      dexamethasone (Dex.), 2) to demonstrate that the induction of cyt. with Dex. in
      liver "rat donor" was transmissible to "recipient rat" after liver
      transplantation. Sixty rats were divided in 5 groups. In group T, a single dose
      of CsA (10 mg/kg) was administered intravenously in 10 rats; in group D, 10 rats
      were treated with Dex (300 mg/kg daily for 4 days) and then received CsA as
      above; in group BN 5 rats were treated with beta-naphthoflavone. Thirty five rats
      underwent a liver transplantation either from "non induced donors" (group G, n =
      11) or from "induced donors with Dex." (group GD, n = 24) followed by CsA
      injection the next day. For each rat, CsA plasma levels were determined by
      radioimmunoassay in 6 samples. Liver microsomes cyt. from samples of the liver of
      donor rats (group G and GD) or after sacrifice (group T, D, BN) were quantitated
      by immunoblot analysis and estimated from densitometric analysis of the blot.
      Mean maximal plasma concentration (Cmax) were 2,822 +/- 997 ng/ml in group T,
      1,447 +/- -458 ng/ml in group D, 2,685 +/- 1,383 ng/ml in group G, 1,337 +/- 713
      ng/ml in group GD and 3,094 +/- 685 ng/ml in group BN. Considering the Cmax and
      the ASC (area under curve), there was a significant difference between all groups
      and separately between groups T and D, G and GD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345702
TI  - [Extracorporeal bio-artificial liver using isolated hepatocytes. An experimental
      study in the rat].
AB  - A new type of bioartificial liver using isolated hepatocytes immobilized in
      alginate beads was developed and its capacity of correcting the metabolic
      deficiency of bilirubin conjugation in Gunn rats was assessed. Hepatocytes were
      isolated from Sprague-Dawley rats using the in situ collagenase perfusion
      technique, and they were then immobilized in Calcium alginate beads. The capacity
      of these immobilized hepatocytes to conjugate in vitro bilirubin was checked as
      compared to monolayer hepatocyte culture. The bioartificial liver consisted in a
      cylindrical bioreactor containing either alginate beads and hepatocytes (test
      group), or only alginate beads (control group). Gunn rats were connected to this
      bioreactor through and extracorporeal circulation system, and "bile samples were
      collected" every hour. Bilirubin mono and biconjugates were dosed in the bile
      using the high-performance liquid chromatography technique. The viability of
      alginate immobilized hepatocytes, determined before and after each experiment,
      was stable at 75%. In the test group, the total conjugate concentration rapidly
      increased to reach a maximum value of 204 +/- 16 microns after 3 hours, while in
      the control group, there were only conjugate traces (1 micron). These results
      show that the bioartificial liver is an efficient means to temporarily correct
      genetic deficiency in Gunn rats. Such a system could be of therapeutic interest
      in case of acute hepatic insufficiency.

PMID- 1345703
TI  - [Beneficial effects of perfusion of atrial natriuretic factor in acute post
      ischemic renal insufficiency in the rat].
AB  - Owing to its capacity of increasing glomerular filtration, potential beneficial
      effects of atrial natriuretic factor (ANF) were assessed during a post ischemic
      acute renal insufficiency in rats. Renal insufficiency was obtained by clamping
      the renal artery during 30 min., and by performing a reperfusion during 2 hours
      in uninephrectomized rats. Three groups were defined: a control group where
      animals were submitted to an operation procedure without renal artery clamping, a
      control group were animals received a physiological serum perfusion (1.5 ml/h)
      during the renal reperfusion time and an experimental group where animals were
      administrated a rat 1-28 ANF perfusion (5 microns/ml in NaCl 0.9%, 1.5 ml/hour)
      during the reperfusion time. Insulin clearance (1.0 + 0.05 ml/h vs 0.7 + 0.05
      ml/h, p < 0.01), and diuresis (32.9 +/- 3.6 microliters/min. vs 7.5 +/- 0.23
      microliters/min., p < 0.01) were significantly higher in rats which were
      administrated a NaCl 0.9% perfusion. Histologically, a significant decrease in
      kidney weight and in he percentage of diseases nephrons was observed after
      reperfusion in ANF treated rats. The results obtained demonstrate that ANF
      perfusion in case of post ischemic acute renal insufficiency in rats improves the
      recovery of renal function and reduces the renal histologic lesions.

PMID- 1345704
TI  - [Experimental sclerosing cholangitis following intrabiliary injection of formol
      in the rat].
AB  - Our study was aimed at assessing the effect on the biliary epithelium of formol
      and hypertonic salt serum solutions used as parasiticide for hydatid cysts of the
      liver in rats. One hundred and forty six rats were administrated an intrabiliary
      injection of isotonic salt serum (control group), of 20% hypertonic salt serum
      and of 0.5% and 2% formol solutions. A histological study performed 3 months
      later did not show any abnormality in the rat control group (n = 11). In the
      hypertonic salt serum group (n = 14) and 0.5% formol group (n = 12), moderate
      lesions of biliary epithelium were observed. After a 2% formol injection, a
      periductal sclerosis was observed in 11 cases out of 16, associated with
      pseudocirrhosis lesions in 4 cases. A sequential histo-immunochemical study did
      not show any histological abnormalities in the rat control group (n = 24). In
      rats which were administrated a 2% formol solution (n = 36), first abnormalities
      were observed as soon as the 7th day with a IA antigen expression at the biliary
      epithelium level. Fibrosis lesions were observed after 2 months. After 9 months,
      the infiltration included only T lymphocytes in direct contact with biliary
      tracts. A cholangiographic study showed a normal aspect in the rat control group
      (n = 11) or in rats having received hypertonic salt serum (n = 11), and stenoses
      of biliary tracts, mainly intrahepatic, in 10 rats out of the 11 of the 2% formol
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345705
TI  - [Rupture of the female urethra in fractures of the pelvic bones. Apropos of 2 new
      cases].
AB  - Female urethra ruptures associated with pelvic ring fractures are exceptionally
      observed. The authors compared these 2 cases (Besancon and Toulon) to already
      published cases. This diagnosis must be contemplated and established by the
      surgeon or in his/her presence using urethral catheterization. The surgical
      approach (most of time abdominoperineal) allows an accurate injury repair and
      prevents from fearsome complications due to late diagnosis and treatment. An
      active attitude following this urological act is highly required, in case of
      osteoarticular injuries, whose instability and rules are currently known.

PMID- 1345706
TI  - [Surgery for lumbar disk hernia after chemonucleolysis. Results and analysis.
      Apropos of 100 cases].
AB  - We studied the clinical results of 100 patients operated after failure of
      chemonucleolytic treatment with chemopapain for lumbosciatica caused by disk
      herniation. Secondary surgical procedures were performed because of persistence
      of sciatic pain and disk herniation visible on CT scan. Post-operative follow-up
      was done at a minimum of one year. Clinical results were analyzed according to
      the criteria of Mac-Naff. Out of 100 patients who were re-operated, there were:
      14% excellent results, 38% good results, 26 mediocre results, and lastly 22%
      failures or worsening of the condition. Thus 52% satisfactory compared to 75-95%
      when surgery is done immediately; 48% of the results were unsatisfactory or worse
      than before. We analyzed the mechanism of action of papain and suggested a
      pathophysiological explanation for these results. We concluded that
      chemonucleolysis with chemopapain cannot be an intermediary step between
      systematic medical treatment and surgical treatment.

PMID- 1345707
TI  - [Prosthesis used in the surgery of the abdominal wall. Focus on a comparative
      experimental protocol: difficulties and limits].
AB  - During many years the use of prosthesis for abdominal wall repair was not
      accepted by all surgeons. Now the laparoscopic repair has brought some surgeons
      to do it nearly systematically and industry proposes new materials. To allow
      comparing new materials the authors have developed an experimental proceeding of
      which they analyse technical difficulties and limits.

PMID- 1345708
TI  - [Colonic perforation during colonoscopy. 100 cases].
AB  - The analysis of 100 cases of colon perforation during colposcopic examinations
      highly demonstrates such a statement. The perforation risk during colposcopies is
      generally of the order of 0.2% for a diagnosis coloscopy. According to the
      statistic data used, it can reach 0.5 to 3% in therapy coloscopy. This is a risk
      inherent to the technique used. It is thus required to analyse the causes and
      take the appropriate measures to reduce it to a minimum. Mortality due to such a
      complication remains high (14%), i.e about 0.015 to 0.1% (#2/10000) of all
      colposcopies. In 11% of the patients, serious sequelae are to be observed. This
      demonstrates the significance of the medico-legal problem set by these
      perforations during colposcopies. The whole personnel responsibility can be
      involved: colposcopist, surgeon, anesthetist and hospital unit.

PMID- 1345709
TI  - [Surgical treatment of ulcerative-necrotizing enterocolitis in premature infants.
      Indications and results; apropos of 50 cases].
AB  - From 1984 to 1991, 50 premature infants needed surgery for necrotizing
      enterocolitis. In 36 cases, surgery was necessary in emergency (weight 700 to
      3,000 g, mean term: 29 weeks). Surgical treatment consisted either in intestinal
      resection associated with enterostomy (n = 26, or enterostomy alone (n = 10). The
      results were as follows: 5 early deaths, 4 late deaths (3 due to extra-digestive
      causes), 22 good results with nutritional recovery after closure of enterostomy.
      At the present time, 5 children need parenteral nutrition or are waiting for
      closure of enterostomy. 14 infants needed a surgical treatment for late
      intestinal stricture (3 to 6 weeks) by resection with enterostomy (n = 7) or with
      immediate anastomosis (n = 7). 13 are alive without digestive sequelae and 1 died
      of neurological disease. According to our experience, early surgical treatment
      consists in enterostomy associated whenever possible with resection of necrotic
      intestine. Late strictures are at best managed by resection with immediate
      anastomosis.

PMID- 1345710
TI  - [Distal splenorenal shunt without deconnection in the prevention of recurrent
      digestive hemorrhage in the cirrhotic patient].
AB  - The emergent treatment of gastrointestinal hemorrhage caused by the rupture of
      esophageal varices in cirrhotic patients is based on sclerotherapy. The
      prevention of frequent recurrence may be an indication of portocaval shunting.
      Over an 8-year period, 72 patients were operated with a distal splenorenal shunt
      without deconnection aimed at preventing gastrointestinal rebleeding. This was
      non-emergent surgery. The Child-Pugh grade was 41 A and 31 B. All patients had an
      angiography, which demonstrated the lack of arterioportal reflux. Operative
      mortality was 2.7%. Actuarial survival at 5 years was of 67%, respectively 71%
      for grade A and 60% for grade B. Patency of the shunt was estimated to be 90%.
      Persistence of hepatopetal flow on control arteriography has been established in
      65% of cases. Rebleeding was observed in 10% of cases, and episodes of
      encephalopathy in 10% as well out of 60 studied cases, 29 presented with a
      chronic increase in ammoniemia (48%). Two risk factors of mortality have been
      demonstrated: age higher than 60 years, and relapse of ethylic intoxication,
      which has been observed in 40% of cases. Later hepatic transplantation has been
      performed in one case, without success. These results are similar to those
      obtained with Warren's procedure. Further development of hepatic transplantation
      may limit its indications.

PMID- 1345711
TI  - [Indications and role of surgery in painful dysfunction syndromes of the
      masticatory apparatus].
AB  - Among the numerous causes of facial neuralgias, the painful dysfunction syndrome
      of the manducatory apparatus corresponds to a frequent etiology whose thorough
      study carried out by a multidisciplinary team over about 500 cases allowed their
      splitting into several evolutive clinical forms. At present, a number of these
      forms which are particularly painful, require a disk surgery (dislocation
      reduction, perforation suture, etc.) and if necessary an articular facet surgery
      (modelling condylectomy, surfacing, etc.). This study specifies the indications
      and prognosis for these surgical operations.

PMID- 1345712
TI  - [Apropos of the report: Gas gangrene of the perineum. Therapeutic reflections
      apropos of 23 cases].

PMID- 1345713
TI  - [Proposal of environmental and biological monitoring and health surveillance of
      the exposed to inhalation anesthetics. Consensus. A Study Group on Occupational
      Exposure to Inhalation Anesthetics].
AB  - The Study Group on Occupational Exposure to Inhalation Anaesthetics of the
      Lombardy Association of Occupational Health and Industrial Hygiene prepared a
      document that was discussed during the Congress "Occupational Risks due to
      Inhalation Anaesthetics", held in Brescia, Italy, on May 12, 1992. The same
      document was then approved by the Directory Council of the Lombardy Association
      of Occupational Health and Industrial Hygiene. Data on environmental
      concentrations of Nitrous Oxide collected from 1989 to 1991 in 269 operating
      rooms of 47 hospitals in Lombardy are reported. The measured levels are
      considerably lower than those collected from the same Study Group from 1985 to
      1987 in 111 operating rooms. The methodologies for exposure control are
      discussed, regarding both environmental and biological monitoring. These two
      techniques are complementary and can be used with standardized methods. The
      review of the literature on the early effects showed, even with some uncertainty
      at the current exposure levels, effects on liver and Central Nervous System.
      Still controversial are the data regarding the reproductive toxicity. Health
      surveillance programs have been organized in the last 5 years in 18 Lombardy
      hospitals and they indicate no cases of pathologies due to inhalation anesthetics
      on 1498 subjects. Operative proposals are suggested on the methodology and the
      frequency of environmental/biological monitoring and health surveillance. The
      "technical limit values" reported in the document from the Italian Ministry of
      Health are also discussed. Finally, research topics are suggested in order to
      assess the early effects of exposure.

PMID- 1345714
TI  - [Measurements and environmental and biological monitoring of occupational
      exposure to inhalation anesthetics].
AB  - This paper reports the data of nitrous oxide (N2O) environmental pollution in 269
      operating rooms of 47 hospitals in Italy in 1989-91. In 40% of the operating
      rooms the N2O concentrations are lower than 50 ppm, limit value proposed by
      Health Council for new operating rooms. In 65.4% of the operating room studied,
      N2O mean environmental concentrations are lower than 100 ppm, value proposed by
      the above-mentioned Health Council as limit value for the already existing
      operating rooms. Concerning the biological monitoring, the authors report several
      N2O data in urine (2193), whose levels confirm the data obtained with
      environmental monitoring. The authors believe that they presently have reliable
      methods to perform biological and environmental monitoring: the two techniques
      are complementary in the assessment of the exposure. The method of measuring N2O
      concentrations as exposure index, both for the environmental and biological
      monitoring, is considered very useful to simplify the performance of the
      analyses. In order to assess exposure more precisely, it is however necessary
      also to determine the environmental and/or biological measure of the other
      different anaesthetics used.

PMID- 1345715
TI  - [Early effects of exposure to anesthetic gases and vapors. A critical review on
      the suitability of several indicators of the effect].
AB  - Apart from a risk excess of liver disease among operating theatre personnel and
      of spontaneous abortion in women exposed during pregnancy, no definitive
      conclusion can be drawn regarding health impairment among anaesthesiology staff.
      However, many studies pointed out that several adverse effects occur as a
      consequence of experimental, therapeutic and occupational exposure to inhalation
      anaesthetics. This paper reviews the early changes of the organ systems
      (hepatobiliary, renal, cardiac, hematopoietic, reproductive systems; immunologic
      functions; cytogenetic effects), which are considered to follow anaesthetics
      exposure, to evaluate their possible use as biological indices of effect. The
      liver microsomal enzyme system has received particular attention with the aim of
      clarifying the mechanisms involved in anaesthetics hepatotoxicity. An increased
      microsomal enzyme activity was observed in experimental conditions and in humans.
      This inductive effect, which reflects metabolic changes affecting liver function,
      is commonly considered the earliest sign caused by exposure to several chemicals
      (other than anaesthetics) and may be evaluated by means of biomarkers, among
      which the measurement of urinary D-glucaric acid excretion is a well established
      non-invasive tool. Urinary D-glucaric acid excretion represents the most
      promising early metabolic effect of the exposure to anaesthetics. However, its
      measurement is not yet suitable as an index of effect for use in biomonitoring
      practice. The main aspects to be studied in the future are the following: (i) the
      evaluation of urinary D-glucaric acid excretion in the acute and chronic exposure
      to low-dose anaesthetics to check the existence of a dose-response relationship;
      (ii) the study of other parameters (urinary enzymes, immunological profile,
      chromosome aberrations) in selected groups of exposed and control subjects, in
      which both exposure and confounding factors (age, gender, life style, former
      diseases) as well as concomitant occupational exposures should be carefully taken
      into account.

PMID- 1345716
TI  - [Neurobehavioral effects of inhalation anesthetics used occupationally: a
      critical analysis].
AB  - Unlike other apparatuses, the potential effects on the nervous system of
      occupational exposure to anaesthetic gases have not been exhaustively reviewed.
      Because of the relevance of these effects, their significance of the quality of
      life of the exposed subjects and of the increased risk inherent in their delicate
      work tasks, these themes deserve the greatest attention. This paper briefly
      examines the data from the international literature as well as the
      neurobehavioral methods employed, underlines the existing gaps of knowledge and
      eventually proposes strategies aimed at filling these gaps of knowledge.

PMID- 1345717
TI  - [Occupational exposure to volatile anesthetics and reproductive effects: a
      bibliographic review of epidemiological studies].
AB  - Up to the early eighties, a variety of epidemiological studies suggest that
      chronic exposure to low doses of anesthetic gases, as occurs in operating rooms,
      is an occupational risk factor for spontaneous abortion and congenital defects.
      Numerous and more recent epidemiologic studies are reviewed; currently it is
      suggested that there is inadequate evidence to conclude that occupational
      exposure to anesthetic gases causes increased rates of spontaneous abortion or
      congenital anomalies. The improvement of environmental conditions, that has
      reduced airborne levels of anesthetic gases in operating rooms, has been critical
      in reducing the risk of abortion and congenital defects. In agreement with recent
      epidemiological reports, we believe that the health surveillance of exposed
      workers must include the study of pregnancy outcome.

PMID- 1345718
TI  - [Health surveillance of workers].
AB  - The main purposes of the health surveillance of workers exposed to anaesthetic
      gases are: a) the finding of disorders either reliable to the exposure or
      incompatible with the activity in the operating theatre; b) the epidemiological
      evaluation of the late effects. Simple and rigorous methods to estimate the
      previous and the current risk are suggested. The main data to be collected during
      the medical examination are indicated. The registration of the data of the
      reproductive function by a protocol of recording is proposed. For the health
      surveillance of workers in Health Care Institution it's advisable to establish an
      interdisciplinary group, referring to a specialist on occupational medicine.

PMID- 1345719
TI  - [Role of inhalation anesthetics in current anesthesiological practice].
AB  - Inhalational anesthetic agents represented for long time the sole or mainly
      anesthetic technique in general anesthesia. In the last twenty years, however,
      their use has been also related to toxicity among operating room personnel,
      chronically exposed to the volatile agents. This toxicity could induce the
      anesthesiologist to give up the volatile anesthetic agents in favour of a total
      intravenous anesthetic technique. Nevertheless well constructed prospective
      studies have clearly demonstrated that there is no significant correlation
      between morbidity index and chronic exposure to inhalational anesthetics.
      Furthermore a valid air exchange in the operating room, as well as more
      appropriate anesthesiologic procedures, have significantly reduced the
      concentration of volatile anesthetic agents in the operating areas. Nowadays
      inhalational anesthetic agents represent one of the different choices to perform
      general anesthesia. The anesthesiologist, however, according to patient's
      physical status and surgical procedure, must choose the anesthetic technique
      compatible with minimal risk both for patient and operating room personnel.

PMID- 1345720
TI  - [Evaluation of the risk of anesthetic gases to exposed subjects with different
      tasks in operating rooms].
AB  - A research was carried out on risk evaluation of workers with different tasks in
      operating theatre. The airborne concentrations were determined by an IR analyzer
      with two distinct sampling lines: the first was placed in surgical zone and the
      second one in anesthesiological zone. The anesthetists resulted more at risk than
      surgical team. Nevertheless when the evaluation was based on N2O urinary
      concentration and data were stratified according to task a prevalent inhalation
      absorption resulted for non medical staff (instrumentist and professional nurse).
      Our data concerning N2O ranged between 95-764 ppm indoor and between 3-92 mcg/l
      in the urines of exposed subjects.

PMID- 1345722
TI  - [Cooperation between the occupational health department and the technical
      assistance office to confront the problem of pollution by anesthetics].
AB  - In the past years the problem related to occupational exposure to anaesthetic
      gases in operating rooms has been dealt with in different ways by each hospital
      administration, and frequently with little cooperation between the health
      departments involved. At the Spedali Civili of Brescia in the five year period,
      1987-1991, a monitoring activity of nitrous oxide (N2O) and halogenated
      anaesthetics was performed in 30 operating rooms. This lead to a noticeable
      reduction of environmental concentrations of these substances. Favourable results
      have been achieved principally by maintenance and/or substitution of
      anesthesiological machine parts. In order to organize and facilitate this program
      a close collaboration was accomplished between the Medical Direction of the
      Hospital and the Occupational Health Department, with the support of the
      Technical Assistance Department.

PMID- 1345721
TI  - [Pollution by nitrous dioxide during diagnostic laparoscopy interventions].
AB  - Here we have outlined the data relative to an environmental survey carried out in
      a laparoscopy clinic at the hospital of Padua, to determine the environmental
      concentration of nitrous dioxide (N2O) used for intra-abdominal inflation during
      diagnostic laparoscopy interventions. The data obtained have revealed cases of
      considerable N2O environmental pollution. This above all, due to spontaneous loss
      of gas during the intervention and to the lack of adequate ventilation systems.

PMID- 1345723
TI  - [Neurobehavioral effects of exposure to anesthetic gases].
AB  - Neurobehavioral studies on operating room personnel exposed to anaesthetic gases
      in hospitals of the Region Lombardia have confirmed findings already reported in
      the literature. There was high subjective symptomatology and reduced efficiency
      at psychologic testing among exposed people with protracted exposure. In this
      group, reaction time was worse at the end of the workshift with respect to the
      beginning. These changes were reversible after removal from exposure. It was
      impossible to establish a clear dose/response relationship due to the difficulty
      to control an important confounding factor, such as stress, in field studies.

PMID- 1345725
TI  - [Evaluation of several neuropsychological parameters in subjects occupationally
      exposed to anesthetics].
AB  - 51 workers, occupationally exposed to anaesthetic gases and vapours (nitrous
      oxide, halothane, and isoflurane), were studied monitoring their environmental
      and biological exposure. Moreover, they were tested for visual reaction times and
      neurobehavioural batteries. There was no evidence of important neurotoxic effects
      nor of neurobehavioural problems with low concentrations of anaesthetics.

PMID- 1345724
TI  - [Anesthetic gases and neuropsychological tests].
AB  - The Authors observed, in a group of 15 subjects working in operating theatres and
      occupationally exposed to anesthetic gases, an increase of simple reaction
      average times and an increase of the latency of the wave V of the brainstem
      auditory evoked potentials. The small number of subjects doesn't allow to draw
      conclusions. Nevertheless the findings agree with first analogous studies. The
      Authors, therefore, think opportune to continue the research to acquire further
      evidence and to ascertain the validity of the current TLV.

PMID- 1345726
TI  - [Prevalence of changes in performance, subjective symptoms and occupational
      dermatitis before and after carrying out improvements in the surgical block of
      the Modena Polyclinic].
AB  - The Preventive Medicine Unit for Personnel in the USL N. 16 of Modena has
      conducted a study to evaluate the prevalence of subjective symptoms and
      professional dermatitis among nurses working in a general surgery operating
      theatre of the Modena "Policlinico" Hospital (36 and 41 employees were studied
      respectively in 1990 and 1991), before and after the installation of gas
      evacuators and a modification in the use of detergent and disinfectant
      substances. The study demonstrates that installation of gas evacuating systems,
      if not supported by an intervention of air-conditioning plant, does not
      sufficiently reduce alterations in subjective symptoms. On the other hand, the
      modifications in the use of detergent and disinfectants has demonstrated a
      favourable reduction in the prevalence of professional dermatitis (from 43% to
      18%; chi2 = 4.35, p = 0.037).

PMID- 1345727
TI  - [Risk of infectious hepatitis and risk of anesthetic gases in operating rooms:
      considerations on 3 cases of chronic hepatic pathology].
AB  - Three subject with professional activity in operating theatre and with a
      diagnosis of chronic viral "C" hepatitis are considered. All cases (Two surgeons
      and an anesthetist) had been continuously exposed to low level of airborne
      anesthetic compounds (Nitrous oxide and halogenated compounds). According to
      possible, but not proved, synergic effects, two cases with a clinical picture of
      active chronic hepatitis were classified as unqualified to specific work. The
      third case, affected by a persistent chronic hepatitis, was admitted to operating
      activities only for four hours a week, i.e. only an operating session a week.
      Hepatitis B and C markers must be always monitored during the medical
      surveillance in exposed people of operating theatre.

PMID- 1345728
TI  - [Urinary measurement of D-glucaric acid in operating room personnel in the Modena
      USL 16 hospitals].
AB  - The Authors describe the results of a research conducted in order to evaluate the
      amount of D-glucaric acid in the urine of 131 operating theatre workers exposed
      to anesthetic gases and in a control group of 25 non-exposed hospital personnel.
      The comparison of the results of the two groups points out a significant
      difference (in the exposed members 60.7 +/- 2.4 mumol/1 to 46.7 +/- 4.3 mumol/l
      [+/- s.e.] in the control group; t-test: p = 0.016). The research also considered
      the influence of certain variables such as age, sex, smoking, alcohol, drug use
      and liver disorders. None of these variables has proven to be of significant
      influence on the D-glucaric acid urinary concentration.

PMID- 1345729
TI  - [Health surveillance of the exposed to anesthetics in the environment: a complete
      program of preventive medicine for health personnel].
AB  - Hospital workers often can be simultaneously exposed to several potentially
      hazardous (biological, chemical, and physical) agents. Consequently the
      environmental controls and the periodic health assessments must be overall and
      systematic, but not too frequent. The authors suggest the establishment of an
      interdisciplinary group, including: Hospital Management, Technical Staff,
      Occupational Physician, Occupational Health Nurses, Environmental Hygienists.

PMID- 1345730
TI  - [Proposal of a health education program].
AB  - Since 1987 at the Spedali Civili of Brescia the problem of anaesthetic gases
      pollution in operating surgery rooms was managed by means of periodical
      environmental monitoring and maintenance of the anaesthesiological equipments.
      The mean nitrous oxide concentrations were generally reduced to values below the
      limits indicated by the Italian Ministry of Health. On the contrary, a low
      participation of the operating room personnel was observed in the health
      surveillance program and this phenomenon is clearly evidenced by the progressive
      decrease of the number of medical examinations. In order to clarify the
      usefulness of health surveillance programs and to promote the adoption of "less
      pollutant" behaviour, a Health Education Program was planned by the Medical
      Administration, in collaboration with the Occupational Health Service and the
      Department of Anesthesiology and Intensive Care. This program will be performed
      at different times, including the administration of a questionnaire, the
      participation at information meetings, the distribution of brochures and the
      evaluation of environmental and biological exposure data before and after the
      education program.

PMID- 1345731
TI  - Magnetic resonance imaging of degenerative diseases of the central nervous
      system.
AB  - MRI enables a better assessment than CT of the bulk loss, i.e. atrophy, which is
      a characteristic feature of all the degenerative diseases of CNS, at least in
      their advanced phases. Moreover, in several of these disorders, proton density,
      balanced and T2 weighted MR images can show symmetric areas of abnormally low or
      high signal intensity in the deep gray nuclei or white matter. Since these signal
      abnormalities are not specific of degenerative diseases of the CNS, their shape
      and distribution have to match those of the histopathological changes
      characteristic of each disease, before they could represent useful ancillary
      signs. Combination of the above MRI findings with appropriate clinical and
      laboratory features will however be crucial to the diagnosis in any single case.

PMID- 1345732
TI  - Magnetic resonance imaging in multiple sclerosis: an overview.
AB  - In less than a decade, Magnetic Resonance Imaging (MRI) has become the
      examination of choice in patients with suspected multiple sclerosis (MS). It is
      the best paraclinical test in assessing dissemination in space of lesions. With
      serial MRI scans, even dissemination in time can be detected. Using serial Gd
      DTPA-enhanced MRI scans, the evolution of lesion can be easily followed. MRI
      studies in MS patients have contributed to shape current ideas about the
      pathogenesis of the disease showing that focal breakdown of the blood-brain
      barrier (BBB) is an early event, if not the first, in the evolution of MS
      lesions. A number of asymptomatic lesions can be detected by MRI in MS patients,
      suggesting an ongoing disease activity independent of the clinical appearance.
      Thus, besides its diagnostic usefulness, MRI will represent the best tool to
      evaluate effectiveness of treatments in therapeutical trials in MS.

PMID- 1345733
TI  - Magnetic resonance imaging in the diagnosis and follow-up of patients with
      multiple sclerosis.
AB  - Magnetic resonance imaging (MRI) has had a major impact on the diagnosis of
      multiple sclerosis (MS). In addition serial MRI studies help to reveal a new
      aspect of measurable activity in MS. The degree of activity shown by serial MRI
      studies is considerably greater than the degree of activity indicated by history
      and physical examination. In addition, the extent of the MRI abnormalities can be
      measured by outlining the lesions and summing the areas of abnormality slice by
      slice. In the future careful, however, clinical follow-up studies must be done in
      order to identify the prognostic implications of these MRI data. At this time MRI
      evaluation techniques are considered a necessary adjunct method of assessment of
      disease activity for MS therapeutic trials. MRI methods are complementary to
      clinical methods and measure an index of extent of disease that is undetectable
      to clinical methods.

PMID- 1345734
TI  - Cognitive and brain imaging measures of multiple sclerosis.
AB  - In this review we will describe the cognitive deficiency in Multiple Sclerosis
      (MS) and analyze the relationship between the performance on neuropsychological
      tests and the anatomofunctional findings assessed by neuroimaging techniques.
      Memory, abstract reasoning, and visuospatial abilities impairments are correlated
      with lesion extension and with corpus callosum atrophy, quantified on MRI. On the
      other hand, in MS patients with cognitive disturbance, PET and SPET studies show
      metabolic alterations and perfusion deficits at the cortical level, particularly
      in the left hemisphere and in the frontal and temporal lobes.

PMID- 1345735
TI  - Notes on the therapy of multiple sclerosis (MS)
AB  - MRI, neuroimmunology and neurobiology have provided significant contributions to
      the rationale of the therapeutic approach in multiple sclerosis. It is clear that
      the ignorance of the etiologic factor has lead to a double treatment policy: the
      first is aimed to control the acute phase of the disease while the second strives
      to block the pathogenetic mechanisms underlying the disease itself and the
      relapses. The author reviews and discusses the latest issues on this topic based
      on his own clinical and laboratory experience.

PMID- 1345736
TI  - The immunopathogenesis of a viral model of multiple sclerosis: Theiler's virus
      induced demyelination.
AB  - Most studies suggest that the pathogenesis of Multiple Sclerosis (MS) is based on
      immune mechanisms of myelin injury. In addition, a viral infection, possibly
      established in the first few years of the patient's life, may be crucial in
      setting the stage for such immune mediated injury when acting on the appropriate
      genetic background. Of the several models of virus-induced demyelination
      described in the last two decades, Theiler's murine encephalomyelitis virus
      (TMEV) infection has emerged as one of the best models for MS.

PMID- 1345737
TI  - Viruses and demyelination in the central nervous system.

PMID- 1345738
TI  - White matter lesions in Creutzfeldt-Jakob disease. A short review.
AB  - This short review takes in consideration the role played by the cerebral white
      matter in Creutzfeldt-Jakob disease (CJD) and analyzes three different hypotheses
      on the meaning of the involvement of the white matter only as secondary
      phenomenon or as primary neuropathological damage related to the causative
      agent(s) of the disease.

PMID- 1345739
TI  - HTLV-I in neurological diseases.
AB  - The human lymphotropic retrovirus type I (HTLV-I) has been recently associated
      with neurological diseases. Antibodies against HTLV-I were found in the sera and
      in the CSF of patients affected by Tropic Spastic Paraparesis (TSP), diffused in
      tropical areas such as Caraibi, south America, Seychelles. A similar clinical
      pattern was found in Japan and was named Human myelopathy (HAM). The virus was
      isolated from mononuclear cells either of the peripheral blood, and of the CSF.
      Molecular studies have shown that the "neurotropic" HTLV-I is similar to that
      associated to T cell leukemia. In vitro studies have shown that tumoral and fetal
      astroglial cells are susceptible to HTLV-I entry. Actually after 7 days, cells
      exposed to HTLV-I showed the virus core protein p19 together with an high
      expression of class II antigens and a disorganization of the GFAP. Multiple
      sclerosis (MS) has also been associated with HTLV-I infection, on the basis of
      finding antibodies against HTLV-I in the sera and in the CSF of some patients.
      However the presence of HTLV-I genome detected by PCR analysis within mononuclear
      cells from peripheral blood lymphocytes of MS patients is still a controversial
      question. The aim of the present review is to critically analyze the role of a
      lymphotropic retrovirus in demyelinating diseases.

PMID- 1345740
TI  - Issues in multiple sclerosis. A focused disease oriented research program.
AB  - This report presents a brief overview of our own focused disease oriented
      research program, and rationale, to find the etiopathogenesis of multiple
      sclerosis (MS). Our hypothesis-driven research proposes that MS is caused by a
      persistent virus located at the edge of active plaques. Further, we propose that
      the immune system has eradicated the virus from inactive plaques or that the
      putative virus has become latent. In 1988 polymerase chain reaction (PCR) was
      reported and it has turned out to be the most sensitive and specific method to
      detect viral nucleic acid sequences in body fluids and tissues. This technique
      may be a breakthrough to test the MS viral hypothesis. Our search is further
      enhanced by the availability of a large collection (from MS Neurospecimen Bank)
      of cryopreserved MS brains and other neurological diseases suitable for PCR. An
      enigma is the specificity of the elevation of intrathecal IgG synthesis (rate and
      oligoclonal bands) that is found in over 99% of clinically definite MS cases. Our
      2 dimensional electrophoresis of cerebrospinal fluid (CSF) IgG shows it to be
      temporally and clonally stable, evidence that intrathecal IgG synthesis is not
      non-specific. Intrathecal IgG synthesis is a marker of IgG synthesizing plasma
      cells in the central nervous system (CNS) and especially in active plaques.
      Another issue is the inclusion in all clinical trials of our objective
      quantitative examination of neurologic function (instrumented tests of functions
      which patients want improved) as well as CSF examination before and after the
      trial to determine the effect of the putative treatment on the polyphasic CNS
      inflammation.

PMID- 1345741
TI  - Blood-brain barrier changes in multiple sclerosis.
AB  - We review the salient published data suggesting blood-brain barrier (BBB) damage
      in multiple sclerosis (MS). We focus attention specifically on: 1) the cerebral
      microvessel involvement in demyelination plaques, 2) the presence of dynamic
      changes in BBB permeability depending on the phase of the disease course, 3) the
      primary role of cerebral endothelial cells in the development of the
      intracerebral immune response.

PMID- 1345742
TI  - On the role of interleukin-2 (IL-2) in multiple sclerosis (MS). IL-2-mediated
      endothelial cell activation.
AB  - Increased serum levels of IL-2 and sIL-2R can be demonstrated in patients with
      active MS, a finding that strongly supports the hypothesis of a systemic T cell
      activation in such patients. However, IL-2 may play a crucial role in MS
      immunopathology by activating endothelial cells, as suggested by the vascular
      leak syndrome complicating hrIL-2 therapy. Early BBB impairment and focal
      perivascular edema that characterize MS lesions may be the effect of an IL-2
      induced cytokine cascade.

PMID- 1345743
TI  - Intrathecal synthesis of proteins: from immunoglobulins to prealbumin.
AB  - The assessment of proteins intrathecal synthesis (ITS) is an essential step in
      the CSF analysis. It can be established qualitatively by different ratios and
      quantitatively by empirical formulae. Schuller and Sagar's formula was proposed
      10 years ago for the calculation of IgG ITS. From this calculation, the antibody
      specific activity of intrathecal immunoglobulins may be also evaluated. The same
      principle may be used for complement components and for different other CSF
      proteins. Two examples (concerning Fibronectin and prealbumin ITS) demonstrate
      the usefulness of this approach, which can be programmed by a computer.

PMID- 1345744
TI  - Tumour necrosis factor-alpha synthesis by cerebrospinal-fluid-derived T cell
      clones from patients with multiple sclerosis.
AB  - T-cell clones derived from the CSF (cerebrospinal fluid) of MS (multiple
      sclerosis) patients have been analysed for the production of interferon-gamma
      (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and
      interleukin-4 (IL-4). Each CSF-T clone (both CD4+ and CD8+) produced substantial
      amounts of IFN-gamma and especially TNF-alpha compared with autologous peripheral
      T clones and liver-infiltrating T clones from patients with chronic active
      hepatitis. The large quantities of TNF produced by CSF-T cell clones suggest an
      important role for this cytokine in MS immunopathogenesis.

PMID- 1345745
TI  - Neurological complications of Lyme borreliosis.
AB  - Lyme disease, like syphilis, a spirochetal infection, can appear with
      exacerbations and remissions in different stages. The clinical picture is marked
      by dermatological, neurological, rheumatic and cardiological complications. PNS
      complications appear in the second and third stage. Tick bite
      meningoradiculoneuritis neuritis (Garin-Bujadoux-Bannwarth-Syndrome),
      characterized by painful asymmetrical sensory and motor dysfunctions and inflamed
      CSF, is a typical manifestation of the second stage. Mononeuritis multiplex
      appearing in conjunction with acrodermatitis chronica atrophicans is a typical
      PNS manifestation of the third stage. CNS involvement may also occur in early and
      late stages of Lyme-Borreliosis, presenting as myelitis or progressive
      encephalomyelitis. Lyme-Borreliosis is a treatable condition, which should not be
      missed in the differential diagnosis of PNS and CNS disorders.

PMID- 1345746
TI  - Neurobiological aspects of glial cells: astrocyte subtypes and the 0-2A glial
      cell lineage.
AB  - Cell culture studies have shown the existence, in the rat CNS, of two populations
      of astrocytes, generally named type-1 and type-2 astrocytes, differing in a
      number of morphological, antigenic and functional features, and belonging to two
      different cell lineages. Type-2 astrocytes seem to derive from a bipotential
      glial progenitor cell (0-2A progenitor) which gives rise also to
      oligodendrocytes. Several epigenetic factors influence the proliferation and the
      differentiation destiny of 0-2A progenitors. Among such factors, heterotypic and
      homotypic glial cell interactions appear to be particularly important.
      Interaction with factors present on the surface of type-1 astrocytes or in their
      extracellular matrix leads to an increased proliferation of 0-2A progenitors and
      facilitates their oligodendroglial differentiation, while homotypic interactions
      among the progenitors induce them to differentiate into oligodendrocytes through
      the secretion of autocrine non mitogenic factors.

PMID- 1345747
TI  - Basics of the magnetic resonance phenomenon.
AB  - Magnetic Resonance is increasing its importance as a diagnostic mean. For an
      effective and accurate MRI practice, new fundamental principles, which are at the
      basis of this phenomenon, must be acquired. In this chapter an extremely
      simplified overview of the physical basics of MRI is introduced, to help the
      readers understand the principles underlying this complex technique. Basic
      physics, T1 and T2 relaxation times, spin echo sequences, which can be acquired
      with the now available units, and tissue characteristics are illustrated. For
      those who are interested in a further and more detailed reading in this field, a
      bibliography is also quoted.

PMID- 1345748
TI  - An in vivo and post mortem MRI study in multiple sclerosis with pathological
      correlation.
AB  - A young woman affected by multiple sclerosis (MS) was examined by magnetic
      resonance (MRI) during a relapse. Three months later the patient died from acute
      pulmonary embolism. An imaging and quantitative MRI study was performed on the
      formalin-fixed brain. Finally, the left hemisphere was examined by light
      microscopy after histological and immunocytochemical staining. While fixation
      significantly reduced T1 and T2 relaxation times, MRI signal and image contrast
      of the fixed brain were satisfactory. Lesion distribution was very similar in
      corresponding MRI slices and histological sections. The post mortem MRI scan and
      pathological study detected several new lesions, as expected from the patient's
      clinical course. Thus, it was possible to evaluate the age of lesions by
      comparing the MRI scans. In this study, signal intensity of MS lesions varied
      according to their histological features, i.e. to their age.

PMID- 1345749
TI  - Chronical administration of anti-DNA antibodies by subcutaneous injection of
      hybridoma clones in BALB/c and NZBxNZW/F1 mice. Experimental model of the
      pathogenic role of DNA in acute lupus disease.
AB  - Several sets of data suggest that specific classes of anti-DNA antibodies could
      be implicated in the genesis of glomerular lesions in SLE. The goal of this work
      is to investigate if this pathogenic role could be related to the antibodies'
      genetic origin--from BALB/c or NZBxNZW/F1 mice--or to their physiological origin-
      induced either by DNA or by polyclonal B cell activation in normal mice. For this
      purpose, anti-DNA antibody hybridoma clones produced from different origins were
      subcutaneously injected in BALB/c or NZBxNZW/F1 female mice, followed by studies
      of immunological parameters and kidney lesions. Results concur that the induced
      anti-DNA antibodies can play a role in fatal disease development, related to
      clonal specificity but not to the way of stimulation which was either polyclonal
      B cell activation or DNA immunization. Also, they emphasize the possible very
      lethal role of serum circulating DNA.

PMID- 1345750
TI  - Reciprocal changes in serum levels of immunoglobulins (IgG, IgA, IgM) and
      complements (C3, C4) in normal pregnancy and after delivery.
AB  - Sequential changes in serum levels of IgG, IgA, and IgM, and C3 and C4 during and
      after pregnancy were studied in 8 healthy women. Serum IgG decreased gradually
      during pregnancy, but increased markedly during the six months following
      delivery. Serum IgA and IgM levels also showed patterns similar to IgG. In
      contrast, C3 and C4 levels increased significantly and reached maximum levels in
      the last trimester during pregnancy, but decreased gradually for six months after
      delivery. Reciprocal changes between immunoglobulins and complements were
      clarified for the first time, and were suggestive of a compensatory
      autoregulatory mechanism in the suppression of the humoral immune system during
      pregnancy.

PMID- 1345751
TI  - Complementation in beta-galactosidase: from protein structure to genetic
      engineering.

PMID- 1345752
TI  - Medical reports on persons claiming compensation for personal injury.
AB  - An audit of one insurance company's files on all employer's liability and third
      party motor claims settled over two years for 5000 pounds or more presented an
      opportunity to review the medical reports on the patients involved. A stratified
      random sample of files on 203 patients contained 602 reports prepared by 400
      consultants. Content analysis was undertaken to evaluate compliance with
      published guidance on reports prepared for medico-legal purposes and to ascertain
      how well reports met recipients' requirements. While clinical topics were well
      covered, generally to a high standard, other functional, psychosocial and
      occupational topics, reflecting the wider clinical and non-clinical frame of
      reference within which lawyers and insurers normally seek information and advice,
      were covered less frequently, extensively and comprehensively--leaving
      considerable scope to improve these aspects of assessment and reporting. Further
      review of this aspect of professional practice should include attention to the
      appropriateness of existing guidance, postgraduate training requirements and the
      involvement of other agencies or professions in some aspects of assessment for
      medico-legal purposes.

PMID- 1345753
TI  - Natural history of insect sting allergy: relationship of severity of symptoms of
      initial sting anaphylaxis to re-sting reactions.
AB  - To examine the postulate that the nature of the symptoms of initial insect sting
      anaphylaxis is related to the risk and severity of subsequent sting reactions,
      the results of field re-stings were analyzed in 220 patients who had had venom
      anaphylaxis and did not receive venom immunotherapy. The incidence of a reaction
      after the first re-sting was 56% in the total group, was more frequent in adults
      (74%) than in children (40%), and was unrelated to the time interval since the
      initial sting reaction. When re-sting reactions did occur, the nature of the
      symptoms was similar to the symptoms of the initial sting reaction. Reactions to
      repeated re-stings tended to be similar. Overall, more severe reactions to re
      stings occurred eventually in 24 patients. These observations confirm the
      frequent self-limiting course of insect sting allergy, especially in children,
      and the repetitive nature of specific anaphylactic symptoms, and the observations
      thus suggest that patients with mild to moderate anaphylactic symptoms probably
      do not require venom immunotherapy.

PMID- 1345754
TI  - A comparison of angioplasty with medical therapy in the treatment of single
      vessel coronary artery disease. Veterans Affairs ACME Investigators.
AB  - BACKGROUND: Despite the widespread use of percutaneous transluminal coronary
      angioplasty (PTCA), only a few prospective trials have assessed its efficacy. We
      compared the effects of PTCA with those of medical therapy on angina and exercise
      tolerance in patients with stable single-vessel coronary artery disease. METHODS:
      Patients with 70 to 99 percent stenosis of one epicardial coronary artery and
      with exercise-induced myocardial ischemia were randomly assigned either to
      undergo PTCA or to receive medical therapy and were evaluated monthly. The
      patients assigned to PTCA were urged to have repeat angioplasty if their symptoms
      suggested restenosis. After six months, all the patients had repeat exercise
      testing and coronary angiography. RESULTS: A total of 107 patients were randomly
      assigned to medical therapy and 105 to PTCA. PTCA was clinically successful in 80
      of the 100 patients who actually had the procedure, with an initial reduction in
      mean percent stenosis from 76 to 36 percent. Two patients in the PTCA group
      required emergency coronary-artery bypass surgery. By six months after the
      procedure, 16 patients had had repeat PTCA. Myocardial infarction occurred in
      five patients assigned to PTCA and in three patients assigned to medical therapy.
      At six months 64 percent of the patients in the PTCA group (61 of 96) were free
      of angina, as compared with 46 percent of the medically treated patients (47 of
      102; P less than 0.01). The patients in the PTCA group were able to increase
      their total duration of exercise more than the medical patients (2.1 vs. 0.5
      minutes, P less than 0.0001) and were able to exercise longer without angina on
      treadmill testing (P less than 0.01). CONCLUSIONS: For patients with single
      vessel coronary artery disease, PTCA offers earlier and more complete relief of
      angina than medical therapy and is associated with better performance on the
      exercise test. However, PTCA initially costs more than medical treatment and is
      associated with a higher frequency of complications.

PMID- 1345755
TI  - Combination therapy with zidovudine and dideoxycytidine in patients with advanced
      human immunodeficiency virus infection. A phase I/II study.
AB  - OBJECTIVE: To evaluate the safety and immunologic and antiviral effects of
      combination therapy with zidovudine and dideoxycytidine (ddC) in patients with
      advanced human immunodeficiency virus type 1 (HIV) infection. DESIGN: A phase
      I/II open-label, dose-ranging study. SETTING: Two AIDS Clinical Trials Group
      units. PATIENTS: Patients (56) with advanced HIV disease. INTERVENTIONS: Patients
      were randomly assigned to one of three paired regimens of zidovudine and ddC. We
      evaluated six dosing regimens, each involving oral administration of the study
      drugs at 8-hour intervals. MEASUREMENTS: Pharmacokinetics, toxicity, CD4 counts,
      p24 antigenemia and clinical end points. MAIN RESULTS: The median follow-up
      period was 40.6 weeks (range, 0.3 to 70 weeks). Neither drug affected the
      pharmacokinetic profile of the other. Episodes of serious hematologic toxicity
      were infrequent, occurring in only 17.9% of patients, and did not differ among
      the regimens (P = 0.15). Severe sensory peripheral neuropathy occurred in two
      patients (one patient each in regimens 1 and 4). One patient receiving regimen 4
      died. The mean maximal increase in CD4 counts exceeded 109 cells/mm3, and 69% of
      patients receiving combinations containing 300 or 600 mg of zidovudine daily had
      an increase in CD4 counts of 50 cells/mm3 or greater. Regimens containing 600 mg
      of zidovudine daily (regimens 2 and 5) were also more likely to result in
      persistent increases in CD4 counts above pretreatment values than were the two
      lowest dose regimens (P = 0.003). The decline in CD4 counts was more rapid, and
      the suppression of the p24 antigenemia was less rapid and less sustained in
      patients receiving the lowest zidovudine dose alone (regimen 6). The addition of
      ddC to regimen 6 (regimen 3) resulted in a slower decline in the CD4 counts (P =
      0.06). CONCLUSIONS: Combination therapy with zidovudine and ddC at the doses
      tested was well tolerated and did not result in toxicity. A daily oral dose of
      150 mg of zidovudine appeared to produce a suboptimal effect on p24 antigenemia
      and CD4 counts. Combination therapy with ddC and higher doses of zidovudine
      produced greater and more persistent effects in patients with advanced HIV
      infection compared with other study regimens and with the results of previous
      trials of zidovudine monotherapy.

PMID- 1345756
TI  - Administration of excitatory amino acid antagonists via microdialysis attenuates
      the increase in glucose utilization seen following concussive brain injury.
AB  - Immediately following concussive brain injury, cells exhibit an increase of
      energy demand represented by the activation of glucose utilization. We have
      proposed that this trauma-induced hypermetabolism reflects the effort of cells to
      restore normal ionic balance disrupted by massive ionic fluxes through
      transmitter-gated ion channels. In the present study, changes in local CMRglc
      following fluid-percussion concussive injury were determined using [14C]2-deoxy-D
      glucose autoradiography, and the effects of in situ administration (via
      microdialysis) of excitatory amino acid (EAA) antagonists [kynurenic acid (KYN),
      2-amino-5-phosphonovaleric acid (APV; 100 microM, 1 mM, and 10 mM), and 6-cyano-7
      nitroquinoxaline-2,3-dine (CNQX; 300 microM, 1 mM, and 10 mM] on glucose
      utilization were investigated. Animals that did not receive dialysis showed a
      remarkable increase (up to 181% of normal control) in cortical glucose
      utilization following injury. In contrast, this high demand for glucose was
      reduced in areas infiltrated with KYN, APV, and CNQX. These results indicate that
      EAA-activated ion channels are involved in the posttraumatic increase in glucose
      utilization, reflecting the energy demand of cells required to drive pumping
      mechanisms against an ionic perturbation seen immediately following the
      concussive injury. The effects of KYN, APV, and CNQX suggest that although all
      subtypes of the glutamate receptor appear to be involved in this phenomenon, N
      methyl-D-aspartate-activated channels may play a major role.

PMID- 1345757
TI  - Postischemic blockade of AMPA but not NMDA receptors mitigates neuronal damage in
      the rat brain following transient severe cerebral ischemia.
AB  - Glutamatergic transmission is an important factor in the development of neuronal
      death following transient cerebral ischemia. In this investigation the effects of
      N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on neuronal damage
      were studied in rats exposed to 10 min of transient cerebral ischemia induced by
      bilateral common carotid occlusion combined with hypotension. The animals were
      treated with a blocker of the ionotropic quisqualate or alpha-amino-3-hydroxy-5
      methyl-4-isoxazole (AMPA) receptor, 2.3-dihydroxy-6-nitro-7-sulfamoyl
      benzo(F)quinoxaline (NBQX), given postischemia as an intraperitoneal bolus dose
      of 30 mg kg-1 followed by an intravenous infusion of 75 micrograms min-1 for 6 h,
      or with the noncompetitive NMDA receptor blocker dizocilpine (MK-801) given 1 mg
      kg-1 i.p. at recirculation and 3 h postischemia, or with the competitive NMDA
      receptor antagonist DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP
      40116), 5 mg kg-1, given intraperitoneally at recirculation. Treatment with NBQX
      provided a significant reduction of neuronal damage in the hippocampal CA1 area
      by 44-69%, with the largest relative decrease in the temporal part of the
      hippocampus. In neocortex a significant decrease in the number of necrotic
      neurons was also noted. No protection could be seen following postischemic
      treatment with dizocilpine or CGP 40116. Our data demonstrate that AMPA but not
      NMDA receptor antagonists decrease neuronal damage following transient severe
      cerebral ischemia in the rat and that the protection by NBQX may be dependent on
      the severity of the ischemic insult. We propose that the AMPA receptor-mediated
      neurotoxicity could be due to ischemia-induced changes in the control mechanisms
      of AMPA receptor-coupled processes or to changes of AMPA receptor
      characteristics.

PMID- 1345758
TI  - Reduction in focal cerebral ischemia by agents acting at imidazole receptors.
AB  - Treatment with the alpha 2-adrenergic antagonist idazoxan (IDA) can provide
      protection from global cerebral ischemia. However, IDA also recognizes another
      class of receptors, termed imidazole (IM) receptors, which differ from alpha 2
      adrenergic receptors and are responsible for the hypotensive actions of some
      centrally acting agents such as the oxazole rilmenidine (RIL). We therefore
      sought to determine whether RIL, an agent highly selective for IM receptors,
      offered protection from focal cerebral ischemia elicited in rat by ligation of
      the middle cerebral artery (MCA). We compared the effects of RIL with the effects
      of IDA and the selective non-IM alpha 2-antagonist SKF 86466 (SKF). In addition,
      we examined whether the neuroprotective effects of RIL and IDA could be
      attributed to changes in local CBF (LCBF). The MCA was occluded and animals
      either received immediate administration of drug while arterial pressure was
      maintained for 1 h or had local CBF increased to 200% of control for 1 h by
      hypercapnia or hypertension. RIL elicited a significant dose-dependent
      preservation of tissue to 33% of control at optimal dose (0.75 mg/kg). IDA (3
      mg/kg) significantly reduced the size of ischemic infarction by 22%. In contrast,
      SKF (15 mg/kg) as well as doubling of LCBF did not preserve ischemic tissue. We
      conclude that both RIL and IDA can reduce focal ischemic infarction but that the
      mechanism does not appear secondary to antagonism of alpha 2-adrenergic receptors
      or elevation of LCBF. Occupation of IM receptors, either in the ischemic zone or
      at remote brain sites, may be responsible for neuroprotection of RIL and IDA.

PMID- 1345759
TI  - Dihydrolipoate reduces neuronal injury after cerebral ischemia.
AB  - It has been shown in vitro that dihydrolipoate (DL-6,8-dithioloctanoic acid) has
      antioxidant activity against microsomal lipid peroxidation. We tested
      dihydrolipoate for its neuroprotective activity using models of hypoxic and
      excitotoxic neuronal damage in vitro and rodent models of cerebral ischemia in
      vivo. In vitro, neuronal damage was induced in primary neuronal cultures derived
      form 7-day-old chick embryo telencephalon by adding either 1 mM cyanide or 1 mM
      glutamate to the cultures. Cyanide-exposed and dihydrolipoate-treated (10(-9)-10(
      7) M) cultures showed an increased protein and ATP content compared with
      controls. The glutamate-exposed cultures treated with dihydrolipoate (10(-7)-10(
      5) M) showed a decreased number of damaged neurons. In vivo, dihydrolipoate
      treatment (50 and 100 mg/kg) reduced brain infarction after permanent middle
      cerebral artery occlusion in mice and rats. Dihydrolipoate treatment (50 and 100
      mg/kg) could not ameliorate neuronal damage in the rat hippocampus or cortex
      caused by 10 min of forebrain ischemia. A comparable neuroprotection was obtained
      by using dimethylthiourea, both in vitro (10(-7) and 10(-6) M) and at a dose of
      750 mg/kg in the focal ischemia models. Lipoate, the oxidized form of
      dihydrolipoate, failed to reduce neuronal injury in any model tested. We conclude
      that dihydrolipoate, similarly to dimethylthiourea, is able to protect neurons
      against ischemic damage by diminishing the accumulation of reactive oxygen
      species within the cerebral tissue.

PMID- 1345760
TI  - Metabolic disorders of the brain in chronic hepatic encephalopathy detected with
      H-1 MR spectroscopy.
AB  - Proton magnetic resonance (MR) spectroscopy of the brain was performed in 11
      patients with chronic hepatic encephalopathy (CHE), and the results were compared
      with those of patients with liver disease but without CHE; clinical control
      subjects with diabetes, uremia, or cortical atrophy; and healthy subjects. The
      technique of water-suppressed stimulated-echo hydrogen-1 MR spectroscopy for
      detection of cerebral glutamate, glutamine, glucose, N-acetylaspartate, choline
      metabolites, (phospho)creatine, and myo-inositol is described. Specific changes
      in the brain of CHE patients included the anticipated elevation in cerebral
      glutamine levels (P less than or equal to .0001), a 23% reduction in choline
      metabolite levels (P less than or equal to .0001), and a more than 50% reduction
      in cerebral myo-inositol levels (P less than or equal to .0001). In four of the
      15 patients with liver disease but without clinical CHE, a significant reduction
      in the myo-inositol level was detected, and in two of these patients an elevation
      in the glutamine concentration was also observed. These findings indicate a role
      for image-guided H-1 MR spectroscopy in the diagnosis and monitoring of both
      overt and preclinical CHE.

PMID- 1345761
TI  - Proton MR spectroscopy for diagnosing hepatic encephalopathy?

PMID- 1345762
TI  - The pylorus-preserving technique in duodenopancreatectomy.

PMID- 1345763
TI  - Analysis of the PvuII restriction fragment-length polymorphism and exon structure
      of the estrogen receptor gene in breast cancer and peripheral blood.
AB  - The presence of estrogen receptor (ER) is a well-known predictor of clinical
      outcome in human breast cancer. We examined the ER gene in 26 primary breast
      cancers (14 ER-positive, 12 ER-negative) to determine if alterations of the gene
      are associated with the ER-negative status. In tumor biopsies and peripheral
      blood DNA obtained from the same patients we analyzed the ER exon structure using
      polymerase chain reaction amplification, restriction endonuclease digestion, and
      agarose gel electrophoresis. All blood and tumor samples, regardless of ER
      status, showed a complete set of eight exons of normal sizes, ruling out
      deletions or rearrangements of the ER gene in excess of +/- 20 nucleotides.
      Previous reports indicate that the two-allele ER PvuII polymorphism could be
      associated with ER expression in breast cancer (Hill et al., Cancer Res., 49: 145
      148, 1989) as well as with patient age at time of tumor diagnosis (Parl et al.,
      Breast Cancer Res. Treat., 14: 57-64, 1989). We localized the PvuII polymorphism
      in intron 1, 0.4 kilobase upstream of exon 2. Sequence analysis showed the
      polymorphism to result from a point mutation (T----C) at the fifth position of
      the restriction site (CATCTG). We determined the PvuII restriction fragment
      length polymorphism genotype in 257 primary breast cancers and 140 peripheral
      blood DNA samples obtained from women without breast cancer. The results indicate
      that the PvuII polymorphism is not associated with ER content or patient age at
      tumor diagnosis.

PMID- 1345764
TI  - Physiological levels of ammonia regulate glutamine synthesis from extracellular
      glutamate in astrocyte cultures.
AB  - The effect of ammonia on glutamate accumulation and metabolism was examined in
      astrocyte cultures prepared from neonatal rat cortices. Intact astrocytes were
      incubated with 70 microM L-[14C(U)]glutamate and varying amounts of ammonium
      chloride. The media and cells were analyzed separately by HPLC for amino acids
      and labelled metabolites. Extracellular glutamate was reduced to 8 microM by 60
      min. Removal of glutamate from the extracellular space was not altered by
      addition of ammonia. The rate of glutamine synthesis was increased from 3.6 to
      9.3 nmol/mg of protein/min by addition of 100 microM ammonia, and intracellular
      glutamate was reduced from 262 to 86 nmol/mg of protein after 30 min. The
      metabolism of accumulated glutamate was matched nearly perfectly by the synthesis
      of glutamine, and both processes were proportional to the amount of added
      ammonia. The transamination and deamination products of glutamate were minor
      metabolites that either decreased or remained unchanged with increasing ammonia.
      Thus, ammonia addition stimulates the conversion of glutamate to glutamine in
      intact astrocyte cultures. At physiological concentrations of ammonia, glutamine
      synthesis appears to be limited by the rate of glutamate accumulation and the
      activity of competing reactions and not by the activity of glutamine synthetase.

PMID- 1345765
TI  - Presynaptic glutamate receptors regulate noradrenaline release from isolated
      nerve terminals.
AB  - The wide-ranging neuronal actions of excitatory amino acids, such as glutamate,
      are thought to be mediated mainly by postsynaptic N-methyl-D-aspartate (NMDA) and
      non-NMDA receptors. We now report the existence of presynaptic glutamate
      receptors in isolated nerve terminals (synaptosomes) prepared from hippocampus,
      olfactory bulb, and cerebral cortex. Activation of these receptors by NMDA or non
      NMDA agonists, in a concentration-dependent manner, resulted in Ca(2+)-dependent
      release of noradrenaline from vesicular transmitter stores. The NMDA-stimulated
      release was potentiated by glycine and was blocked by Mg2+ and selective NMDA
      antagonists. In contrast, release stimulated by selective non-NMDA agonists was
      blocked by 6-cyano-7-nitroquinoxaline-2,3- dione, but not by Mg2+ or NMDA
      antagonists. Our data suggest that the presynaptic glutamate receptors can be
      classified pharmacologically as both the NMDA and non-NMDA types. These
      receptors, localized on nerve terminals of the locus ceruleus noradrenergic
      neurons, may play an important role in interactions between noradrenaline and
      glutamate.

PMID- 1345766
TI  - Transmitter-like basal and K(+)-evoked release of 3,4-dihydroxyphenylalanine from
      the striatum in conscious rats studied by microdialysis.
AB  - Using microdialysis and HPLC, characteristics of the release of endogenous 3,4
      dihydroxyphenylalanine (DOPA) from striatum in conscious rats were studied in
      comparison with those of 3,4-dihydroxyphenylethylamine (dopamine; DA). Purified L
      aromatic amino acid decarboxylase (AADC) converted a putative peak of DOPA to DA.
      The retention time of DOPA differed from that of DA and major metabolites of DA
      and norepinephrine. The DOPA peak of dialysates comigrated with that of authentic
      DOPA when the pH of the HPLC buffer was modified. The ratio of the basal release
      of DOPA:DA was 1:2. 3-Hydroxybenzylhydrazine (NSD-1015; 100 mg/kg, i.p.), an AADC
      inhibitor, markedly increased the basal release of DOPA but produced no effect on
      DA. The basal release of DOPA was markedly decreased by alpha-methyl-p-tyrosine
      (200 mg/kg, i.p.), substantially tetrodotoxin (1 microM) sensitive, and Ca2+
      (removal plus 12.5 mM Mg2+ addition) dependent. Fifty millimolar K+ released DOPA
      and this release was also Ca2+ dependent. These characteristics of the basal and
      evoked release of DOPA were similar to those of DA. The ratio of the evoked
      release of DOPA:DA was 1:3. These results indicate that DOPA is released under
      physiological conditions and by K(+)-induced depolarization in a manner similar
      to that for transmitter DA from striatum in freely moving rats.

PMID- 1345767
TI  - Enhanced tyrosine hydroxylation in hippocampus of chronically stressed rats upon
      exposure to a novel stressor.
AB  - We have used microdialysis to measure the in vivo level of tyrosine hydroxylation
      in hippocampus of the freely moving rat. An inhibitor of aromatic amino acid
      decarboxylase, NSD-1015, was administered through the dialysis probe and the
      resulting accumulation of 3,4-dihydroxyphenylalanine (DOPA) in extracellular
      fluid of hippocampus was quantified. Administration of the tyrosine hydroxylase
      inhibitor, alpha-methyl-p-tyrosine, decreased extracellular DOPA to undetectable
      level. In addition, both systemic and local application of clonidine, an alpha 2
      adrenergic agonist, produced a decrease in extracellular DOPA. In response to
      acute tail shock, a significant increase in extracellular DOPA was observed.
      Thus, it appears that in vivo accumulation of DOPA after local administration of
      NSD-1015 provides a reliable index of hippocampal tyrosine hydroxylation. We have
      used this technique to investigate whether prior exposure to chronic stress
      alters the in vivo level of tyrosine hydroxylation in hippocampus under basal
      conditions as well as in response to a novel stressor. In rats previously exposed
      to chronic cold stress, the basal accumulation of extracellular DOPA did not
      differ from naive controls. Acute tail shock, however, produced a significantly
      greater and more prolonged elevation in extracellular DOPA of chronically
      stressed rats. These data suggest that enhanced biosynthetic capacity of
      noradrenergic terminals may be one mechanism underlying adaptation to chronic
      stress.

PMID- 1345768
TI  - An activation of synaptosomal Na+,K(+)-ATPase by a novel dibenzoxazepine
      derivative (BY-1949) in the rat brain: its functional role in the
      neurotransmitter uptake systems.
AB  - In search of factors mitigating the final outcome of ischemic and epileptic brain
      damage, we tested a novel dibenzoxazepine derivative (BY-1949), as the compound
      has been shown to be effective under these two conditions. First, using rat
      brain, we assessed whether or not BY-1949 affects the Na+,K(+)-ATPase activity.
      Although in vitro applications of either BY-1949 or its three major metabolites
      did not cause any apparent effects, both acute and chronic oral administrations
      of the compound (10 mg/kg) invariably increased the Na+,K(+)-ATPase activity in
      the synaptosomal plasma membranes by increasing Vmax values. Second, it was shown
      by this study that the drug treatment caused marked increases in the uptake of
      both glutamic acid and gamma-aminobutyric acid into the synaptosomes. These
      results suggest that the activity against ischemic/epileptic brain damage by BY
      1949 is explicable, at least partly, in terms of improvement of ionic
      derangements across the neural membranes via Na+,K(+)-ATPase activation.

PMID- 1345769
TI  - Alzheimer beta/A4-amyloid precursor protein: evidence for putative amyloidogenic
      fragment.
AB  - Recombinant baculovirus was used to overexpress human Alzheimer beta/A4-amyloid
      precursor protein (APP) in Spodoptera frugiperda (Sf9) cells. Lysates of these
      cells were then analyzed for the presence of carboxyl-terminal fragments of APP
      by an immunoblotting assay using either an antibody against the APP cytoplasmic
      domain (rabbit anti-human 695APP645-694) or an antibody against the amino
      terminus of beta/A4-amyloid (rabbit anti-human 695APP586-606). Anti-human
      695APP645-694 identified APP holoprotein, a 25-kDa species, and a prominent group
      of carboxyl-terminal fragments of 17, 16, and 14 kDa, whereas anti-human
      695APP586-606 identified APP holoprotein and a single prominent low-molecular
      mass protein species comigrating with the 17-kDa carboxyl-terminal fragment
      identified by anti-human 695APP645-694. No immunoreactive species was detected at
      these molecular mass positions when either antibody was used for analysis of
      lysates of either uninfected Sf9 cells or Sf9 cells infected with wild-type
      Autographa californica baculovirus. For each antibody, specific immunoreactivity
      was abolished by preabsorption with the corresponding peptide immunogen. The
      incorporation of a beta/A4-amyloid amino-terminal epitope into a 17-kDa fragment
      of APP suggests that, in the baculoviral overexpression system, the
      electrophoretic microheterogeneity of APP carboxyl-terminal fragments is due, at
      least in part, to alternative proteolysis of APP. If such carboxyl-terminal
      fragments of APP containing an intact beta/A4-amyloid domain are produced in
      human brain, then they may represent intermediates in the conversion of APP to
      deposited beta/A4-amyloid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345770
TI  - Activation and multiple-site phosphorylation of tyrosine hydroxylase in perfused
      rat adrenal glands.
AB  - Tryptic digestion of tyrosine hydroxylase (TH) isolated from rat adrenal glands
      labeled with 32Pi produced five phosphopeptides. Based on the correspondence of
      these phosphopeptides with those identified in TH from rat pheochromocytoma
      cells, four phosphorylation sites (Ser8, Ser19, Ser31, and Ser40) were inferred.
      Field stimulation of the splanchnic nerves at either 1 or 10 Hz (300 pulses)
      increased 32P incorporation into TH. At 10 Hz, the phosphorylation of Ser19 and
      Ser40 was increased, whereas at 1 Hz, Ser19, Ser31, and Ser40 phosphorylation was
      increased. Stimulation at either 1 or 10 Hz also increased the catalytic activity
      of TH, as measured in vitro (pH 7.2) at either 30 or 300 microM
      tetrahydrobiopterin. Nicotine (3 microM, 3 min) increased Ser19 phosphorylation,
      vasoactive intestinal polypeptide (10 microM, 3 min) increased Ser40
      phosphorylation, and muscarine (100 microM, 3 min) increased TH phosphorylation
      primarily at Ser19 and Ser31. Vasoactive intestinal polypeptide, but not nicotine
      or muscarine, mimicked the effects of field stimulation on TH activity. Thus, the
      regulation of rat adrenal medullary TH phosphorylation by nerve impulses is
      mediated by multiple first and second messenger systems, as previously shown for
      catecholamine secretion. However, different sets of second messengers are
      involved in the two processes. The action of vasoactive intestinal polypeptide as
      a secretagogue involves the mobilization of intracellular calcium, whereas its
      effects on TH phosphorylation are mediated by cyclic AMP. This latter effect of
      vasoactive intestinal polypeptide and the consequent increase in Ser40
      phosphorylation appear to be responsible for the rapid activation of TH by
      splanchnic nerve stimulation.

PMID- 1345771
TI  - Effect of experimental diabetes on the catecholamine metabolism in rat brain.
AB  - The levels of epinephrine, norepinephrine, and dopamine and the activities of
      tyrosine hydroxylase and monoamine oxidase were estimated in four regions of rat
      brain during alloxan-induced hyperglycemia and insulin-induced hypoglycemia.
      Catecholamine levels were estimated by HPLC, and the insulin levels were
      quantified by radioimmunoassay. The results demonstrated significant increases in
      the activities of the metabolizing enzymes and levels of catecholamines during
      experimental conditions. The levels of catecholamines were highest in the
      cerebral hemispheres, the region associated with high activities of the
      metabolizing enzymes. Insulin-induced hypoglycemia caused a decrease in the
      activities of the metabolizing enzymes followed by their recovery within 2 h.

PMID- 1345772
TI  - Immunohistochemical study of HER-2/neu, epidermal growth factor receptor, and
      steroid receptor expression in normal and malignant endometrium.
AB  - HER-2/neu oncogene protein, epidermal growth factor receptor, progesterone
      receptor, and estrogen receptor were examined immunohistochemically in specimens
      of normal and neoplastic endometrium. Tissues obtained at the time of
      hysterectomy were snap-frozen at liquid nitrogen temperature and serially
      sectioned at 4 microns. Normal endometrial epithelial cells stained with anti
      epidermal growth factor receptor and anti-HER-2/neu with intensities graded from
      0 to 3+. Of the 49 endometrial malignancies studied, seven (14%) contained tissue
      exhibiting HER-2/neu staining in excess (4+) of any of the normal tissues or the
      other 42 cancer specimens. Expression of both HER-2/neu and steroid receptors was
      heterogeneous within these seven tumors. To examine this heterogeneity more
      closely, sections of these and other tumors were double-stained for HER-2/neu and
      progesterone receptor. It was found that the cells exhibiting 4+ HER-2/neu
      staining were progesterone receptor-negative. Conversely, cells that were
      progesterone receptor-positive within the same specimen exhibited HER-2/neu
      immunostaining equal to or less than 3+. All specimens containing 4+ HER-2/neu
      tissue were graded 1 or 2 adenocarcinomas, stage I. Thus, there is an inverse
      relationship between overexpression of HER-2/neu and progesterone receptor in
      endometrial cancer. On the other hand, overexpression of HER-2/neu in endometrial
      cancer does not seem to be related to loss of other differentiated
      characteristics. The prognostic value of these observations awaits continued
      study.

PMID- 1345773
TI  - CD4 counts and HIV-related deaths.

PMID- 1345774
TI  - CD4 counts and HIV-related deaths.

PMID- 1345775
TI  - Comparison of black coral skeleton and insect cuticle by a combination of carbon
      13 NMR and chemical analyses.
AB  - Cross-polarization, magic-angle spinning 13C NMR spectra of skeletal components
      of individual colonies of the New Zealand black coral, Antipathes fiordensis,
      have a marked similarity to spectra of the sclerotized exoskeleton of the adult
      tobacco hornworm, Manduca sexta. NMR analysis estimates the organic content of
      the load-bearing skeletal base of A. fiordensis as 70% protein, 10% chitin, 15%
      diphenol, and 5% lipid by weight, and that of M. Sexta moth cuticle as 60%
      protein, 20% chitin, 15% diphenol, and 5% lipid. The younger pinnules or tips of
      A. fiordensis are less than 3% diphenol by weight. The only diphenols extracted
      from coral skeleton by hydrochloric acid are 3-(3,4-dihydroxyphenyl)-DL-alanine
      (DOPA) and 3,4-dihydroxybenzaldehyde (DOBAL), while the predominant diphenols in
      acid extracts of insect cuticles are N-acyldopamines. More DOPA is found in the
      base than in the tips of A. fiordensis and it appears to be a peptidyl component
      of coral skeletal protein. The oxidation of DOPA and DOBAL to quinones may
      provide mechanical stabilization of the coral skeleton by cross-linking of
      structural proteins to other proteins or to chitin.

PMID- 1345776
TI  - Fourth Workshop on Cells and Cytokines in Bone and Cartilage. 11-14 January 1992,
      Davos, Switzerland. Abstracts.

PMID- 1345777
TI  - Mechanical deformation of vessel wall and shear stress determine the basal
      release of endothelium-derived relaxing factor in the intact rabbit coronary
      vascular bed.
AB  - We investigated the mechanisms that are responsible for the basal release of
      endothelium-derived relaxing factor (EDRF), which is likely to be identical with
      nitric oxide, in the intact coronary circulation. The increase in cGMP content of
      platelets passing through the coronary bed of the isolated rabbit heart was used
      as an index of EDRF release. Platelet cGMP content after passage through the
      heart under control conditions (flow rate of 20 ml/min) amounted to 0.50 +/- 0.10
      pmol/mg protein. Inhibition of endothelial nitric oxide synthesis by 30 microM NG
      nitro-L-arginine (L-NNA) reduced this amount by more than 60%. Increasing flow
      rate from 20 ml/min to 40 and 60 ml/min led to flow-dependent dilation as
      reflected by the subsequent drop in perfusion pressure after an initial rise. The
      flow-dependent dilation was associated with a significant increase in the
      normalized platelet cGMP content. L-NNA abolished completely both the flow
      dependent dilation and the increase in platelet cGMP content. Increasing shear
      stress by a strong vasoconstriction (1 nM endothelin-1) at constant flow was also
      accompanied by a 2.5-fold increase in platelet cGMP content. To investigate
      whether mechanical forces applied to the vascular wall by the myocardial
      contraction cycle were also a stimulus for EDRF release, cardiac arrest was
      induced by a continuous infusion of mepivacaine (final concentration, 0.02%).
      Under these conditions, a decrease in platelet cGMP content comparable to that
      after nitric oxide synthesis inhibition was observed in the arrested
      heart.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345778
TI  - Mechanism of augmented rate of left ventricular filling during exercise.
AB  - At rest, most of left ventricular (LV) filling occurs early in diastole. This LV
      filling occurs in response to the pressure gradient produced as LV pressure falls
      below left atrial (LA) pressure. Because mitral valve flow occurs in response to
      an LA to LV pressure gradient, augmented diastolic mitral valve flow during
      exercise may be due to an increased mitral valve pressure gradient resulting from
      a rise in LA pressure and/or a fall in LV early diastolic pressure. Accordingly,
      we studied 13 conscious dogs, instrumented to measure micromanometer LV and LA
      pressures, and determined LV volume from three ultrasonic dimensions during
      exercise. The animals ran on a treadmill for 8-15 minutes at 5-8 miles/hr. With
      reflexes intact, during exercise, the heart rate increased from 116 +/- 20 to 189
      +/- 24 beats per minute (mean +/- SD, p less than 0.01), the maximum rate of
      change of LV volume (dV/dtmax) increased from 185 +/- 44 to 282 +/- 76 ml/sec (p
      less than 0.01), the ejection fraction and cardiac output increased, and the
      duration of diastole decreased from 296 +/- 83 to 162 +/- 71 msec (p less than
      0.01). Mitral valve opening pressure, mean LA pressure (10.9 +/- 4.4 versus 10.2
      +/- 3.9 mm Hg, p = NS), and LV end-diastolic pressure (12.8 +/- 4.8 versus 13.1
      +/- 3.3 mm Hg, p = NS) were all relatively unchanged. The time constant of the
      fall of isovolumic LV pressure decreased from 28 +/- 3.3 to 21 +/- 4.4 msec (p
      less than 0.05). The early diastolic portion of the LV pressure-volume loop was
      shifted downward during exercise, with the minimum LV pressure decreasing from
      3.3 +/- 2.8 to -2.8 +/- 3.4 mm Hg (p less than 0.05) and the maximum mitral valve
      pressure gradient increasing from 5.5 +/- 1.7 to 11.8 +/- 3.5 mm Hg (p less than
      0.01). A similar downward shift of the early diastolic portion of the LV pressure
      volume loop was produced by infusion of dobutamine (6 micrograms/kg/min i.v.) at
      rest, as well as by exercise when the heart rate was held constant by right
      ventricular pacing at 190-210 beats per minute. The downward shift during
      exercise was prevented by beta-blockade (metoprolol, 0.5 mg/kg i.v.). We conclude
      that during exercise, sympathetic stimulation and tachycardia produce a downward
      shift of the early diastolic portion of the LV pressure-volume loop.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1345779
TI  - Pulsatile gonadotropin-releasing hormone modifies polyadenylation of gonadotropin
      subunit messenger ribonucleic acids.
AB  - Gonadotropin subunit mRNA levels rise after castration, coincident with a period
      of increased GnRH input to the pituitary. In addition to increased levels of
      gonadotropin mRNAs, we observed that the sizes of the alpha and LH beta mRNAs
      were increased after ovariectomy (OVX) of rats. To determine whether these
      changes occurred in the 5' (alternate transcriptional start site or splicing)- or
      3' (altered polyadenylation)-end of the molecules, mRNAs were cleaved using
      oligonucleotide-directed RNase-H digestion, and the fragments were analyzed by
      Northern blot, using probes specific to the 5'- and 3'-segments of each
      transcript. After OVX, there was no change in the sizes of the 5'-segments of LH
      beta, FSH beta, and alpha-subunit mRNAs. However, the LH beta and alpha-subunit
      3'-fragments were increased in size, indicating a shift to more adenylated forms
      of the LH beta and alpha transcripts. For FSH beta, the 3'-fragment bands were
      more diffuse than for LH beta or alpha-subunit, and no alteration in the lengths
      of FSH beta poly(A) tails were detected. A perifused pituitary cell system was
      used to determine whether pulses of GnRH were sufficient to cause modifications
      of polyadenylation. GnRH was administered as hourly 10-nM pulses for 4-12 h. Time
      dependent increases in the sizes of LH beta and alpha-subunit mRNAs were observed
      in GnRH-treated cells compared to cells receiving no GnRH. Changes in the lengths
      of LH beta and alpha-subunit mRNAs were shown to be due to increased
      polyadenylation, and there was no observable change in polyadenylation of FSH
      beta mRNA. In addition, no changes were observed in the size of the 3'-fragments
      of PRL or beta-actin mRNAs. These data demonstrate that pulsatile GnRH
      administered in vitro elicits specific increases in the lengths of the LH beta
      and alpha-subunit mRNA poly(A) tails. Similar changes occur after OVX. Thus, in
      addition to transcriptional stimulation of the gonadotropin gene, GnRH modifies
      gonadotropin mRNAs at a posttranscriptional level.

PMID- 1345780
TI  - Short-term adult exposure to estradiol feminizes the male pattern of spontaneous
      and growth hormone-releasing factor-stimulated growth hormone secretion in the
      rat.
AB  - Experimental evidence indicates that the neonatal gonadal steroid environment is
      an important determinant of the sexual dimorphism of GH secretion and body
      growth. However, the influence of the sex steroids in GH control during adult
      life and their mechanism/site of action are largely unknown. In the present study
      we examined the effects of adult gonadectomy (GNX) and short term adult exposure
      to 17 beta-estradiol (E2) on both spontaneous and GRF-stimulated GH release in
      free-moving adult male rats. The rate of body weight gain was also monitored. GNX
      (3 weeks postoperatively) resulted in a 2-fold reduction in GH pulse amplitude
      compared to that in sham-operated control rats, but did not significantly alter
      the GH nadir or the interpeak interval. Exposure to E2 (sc implants) for 4 days
      markedly disrupted the spontaneous GH secretory profile of both sham-operated and
      GNX rats; E2-treated animals exhibited a striking elevation (4- to 20-fold) of GH
      trough levels and a significant decrease in GH interpeak interval, remarkably
      similar to the typical female rat GH secretory profile. The augmentation in both
      GH nadir and GH pulse frequency was evident as early as 12 h after a single sc
      injection of E2 valerate. In sham and GNX rats bearing control implants, the GH
      response to 1 micrograms rat GRF-(1-29)NH2, iv, was significantly greater when
      GRF was administered at peak (1100 h) than at trough (1300 h) times of GH
      secretion; the latter is known to be due to antagonism by the cyclical increased
      release of endogenous somatostatin (SRIF) in the male rat. Treatment with E2
      abolished this time-dependent difference in both groups and produced a regular
      pattern of GH responsiveness to GRF similar to that typically observed in the
      female rat, thus suggesting that E2 has altered the pattern of hypothalamic SRIF
      secretion from a cyclic to a more continuous mode of release. Chronic exposure to
      E2 for 2 weeks resulted in an almost 6-fold inhibition of the rate of body weight
      gain in sham-operated male rats to levels comparable to those in normal adult
      female rats. Taken together, these results demonstrate that short term exposure
      to E2 during adult life can profoundly feminize the male pattern of spontaneous
      and GRF-stimulated GH secretion, as well as rate of somatic growth.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1345781
TI  - Identification of genetic markers flanking the locus for maturity-onset diabetes
      of the young on human chromosome 20.
AB  - A systematic search for genetic linkage with maturity-onset diabetes of the young
      (MODY) as expressed in the R.-W. pedigree has been carried out. Evidence for
      linkage was found with restriction-fragment-length polymorphism loci that map to
      human chromosome 20. Two-point linkage analysis with CRI-L1214 (D20S16) and MODY
      gave a log of the odds (lod) score of 4.16 at theta = 0.08. Multipoint linkage
      analysis with nine restriction-fragment-length polymorphism loci resulted in a
      lod score of 4.81 with the MODY locus in an approximately 20-cM region bounded by
      D20S16 and D20S14-D20S18. Examination of the pattern of MODY segregation suggests
      that additional factors, possibly genetic could be involved in the age of onset
      of the disease.

PMID- 1345782
TI  - The vascular order of islet cellular perfusion in the human pancreas.
AB  - The vascular order of pancreatic islet cellular perfusion is important in the
      intraislet regulation of hormone secretion. Establishment of the sequence of
      interaction is fundamental to understanding the physiology and pathophysiology of
      the human islet. Intraislet insulin from the beta-cell regulates both net hormone
      secretion and pulsatile secretion from alpha- and delta-cells. In terms of
      vascular perfusion, the delta-cell is perfused last and does not directly affect
      alpha- or beta-cells in humans.

PMID- 1345783
TI  - Effects of dopamine and somatostatin on pulsatile pituitary glycoprotein
      secretion.
AB  - The hypothalamic factors dopamine (DA) and somatostatin (SRIH) inhibit pituitary
      glycoprotein secretion, but little is known regarding the effects of these
      factors on glycoprotein pulses. To address this question, 12 healthy volunteers
      underwent frequent blood sampling over 12 h at baseline and during 12-h infusions
      of DA and/or SRIH. TSH, LH, FSH, and alpha-subunit (alpha) levels were measured
      in all samples, and hormone pulses were located by Cluster analysis. Both DA and
      SRIH suppressed TSH pulse amplitude by 70%, while SRIH decreased TSH pulse
      frequency as well. Both infusions decreased LH pulse amplitude by 30-35%, but had
      no effect on pulse frequency. In contrast, neither infusion significantly altered
      FSH pulse parameters, although mean FSH levels declined 15%. DA had no effect on
      pulsatile alpha secretion, while SRIH decreased alpha pulse frequency. Serum
      thyroid hormone levels declined during both infusions, but there were no major
      changes in serum sex steroid levels. Thus, the hypothalamic inhibitory factors DA
      and SRIH had divergent effects on glycoprotein hormone pulses. The major effects
      on pulse amplitude, rather than frequency, imply that these factors do not play
      major roles in the generation of glycoprotein pulses, although SRIH may directly
      affect the TSH and alpha pulse generators.

PMID- 1345784
TI  - Immunogenetic and hormonal study of cryptorchidism.
AB  - Ninety-four cryptorchids, 50 monolateral and 44 bilateral, aged from 2-9.4 yr
      (mean, 5.1 +/- 0.5 yr), were studied for the hormonal and immunogenetic profile.
      Pituitary-gonadal function was studied by evaluation of basal and peak GnRH
      stimulated serum FSH and LH. In 83 cases, the serum testosterone (T) level was
      measured before and after CG treatment. No significant differences, between
      patients and age-matched controls, were found in either FSH or LH levels, whether
      under basal conditions or after GHRH stimulation. The mean basal serum T level
      was similar in mono and bilateral cryptorchids and in controls but, on the 15th
      day after treatment, it was significantly lower in the bilateral cryptorchids (P
      less than 0.05). CG administration led to testicular descent in 42 patients (23
      with monolateral and 19 with bilateral cryptorchidism) and failed in 41 (21 with
      monolateral and 20 with bilateral cryptorchidism), independently of T increase.
      Immunogenetic investigation demonstrated that HLA-A11 and A23 were significantly
      overrepresented in the whole group of cryptorchids in comparison with the
      controls (P = 0.004 and P = 0.0123, respectively). HLA-A11 was more common in the
      bilateral form (P less than 0.05), whereas HLA-A29 was more frequent in the
      monolateral one (P less than 0.05). Forty percent of the bilateral cryptorchids
      with unsuccessful treatment had the HLA-A11 allele (P less than 0.01) and 70% the
      HLA-DR5.

PMID- 1345785
TI  - CD4+ subset regulation in viral infection. Preferential activation of Th2 cells
      during progression of retrovirus-induced immunodeficiency in mice.
AB  - Progressive lymphoproliferation and increasingly severe immunodeficiency are
      prominent features of a syndrome, designated mouse AIDS, which develops in
      susceptible strains of mice infected with the mixture of murine leukemia viruses,
      termed LP-BM5. Development of splenomegaly and lymphadenopathy, caused primarily
      by increases in B cell immunoblasts, requires the presence of CD4+ T cells and is
      assumed to be mediated by lymphokines produced by these cells inasmuch as
      progression of disease is markedly inhibited by treatment of infected mice with
      cyclosporin A. Studies of spleen cells from infected mice revealed spontaneous
      production of cytokines (IFN-gamma, IL-2, IL-4, IL-5, and IL-10) characteristic
      of Th0 (or a mixture of Th1 and Th2) T helper cells at 1 wk after infection. At
      later times, IFN-gamma and IL-2, characteristic products of Th1 helper clones,
      were expressed poorly, either spontaneously or after stimulation of cells with
      Con A. In contrast, IL-4, IL-5, IL-6, and IL-10, cytokines typically synthesized
      by Th2 cells, were produced in response to Con A or spontaneously through 18 wk
      post-infection. Increased serum IgE levels and enhanced IL-10 mRNA expression
      were consistent with expression of Th2 cytokines at biologically significant
      levels in vivo. Selective depletion of T cell subsets before stimulation with Con
      A showed that CD4+ T cells were the primary source of IL-2, IL-4, IL-10, and, to
      a lesser extent, IFN-gamma in spleens and lymph nodes of normal or infected mice.
      These results suggest that persistent activation of CD4+ T cells with the
      lymphokine profile of Th2 helper clones is responsible for chronic B cell
      stimulation, down-regulation of Th1 cytokines, and impaired CD8+ T cell function
      in mouse AIDS. This provides the first demonstration that, like many parasitic
      infections, viruses encoding potent antigenic stimuli can markedly affect the
      balance of Th subset expression.

PMID- 1345786
TI  - Yersinia enterocolitica produces superantigenic activity.
AB  - We have recently observed that antigenic preparations from Yersinia
      enterocolitica are capable of inducing strong proliferative responses in normal
      murine spleen cell cultures. As a consequence of this observation, we evaluated
      whether Yersinia-derived Ag possess superantigenic activity. Stimulatory activity
      can be found in culture supernatants, as well as membrane and cytoplasmic
      fractions of Y. enterocolitica. Cell depletion studies indicate that the primary
      responding cell is a CD4+ T cell, which requires the presence of APC for
      responsiveness to Y. enterocolitica Ag. Furthermore, these APC must express MHC
      class II Ag, as evidenced by the fact that either antibody depletion of class II+
      APC or addition of anti-class II antibodies (that block class II Ag on the
      surface of APC) eliminates the proliferative response. Evaluation of TCR usage by
      BALB/c T cells responsive to Y. enterocolitica revealed that those T cells
      bearing V beta 3, 6, and 11 and possibly 7 and 9 were expanded after exposure to
      Y. enterocolitica Ag preparations. By using a panel of T cell hybridomas, we have
      shown that hybridomas bearing V beta 3, 7, 8.1, 9, and 11 but not 2, 8.2, 8.3,
      and 13 respond to Yersinia. When cytoplasmic fractions of Y. enterocolitica were
      subjected to column chromatography, proliferative activity was enriched
      approximately 27-fold, and the elution characteristics of the active material
      suggest that it possesses hydrophobic regions and is, therefore, probably
      membrane associated. These data indicate that Y. enterocolitica produces
      antigenic material that has properties consistent with those of T cell
      superantigens.

PMID- 1345787
TI  - Generation propagation, and targeting of human CD4+ helper/killer T cells induced
      by anti-CD3 monoclonal antibody plus recombinant IL-2. An efficient strategy for
      adoptive tumor immunotherapy.
AB  - We developed a culture system for the rapid generation of CD4+ T cells that have
      both helper and killer functions. CD4+ T cells isolated from human PBL did not
      proliferate or develop significant cytotoxicity when treated with rIL-2 because
      of the lack of p75 IL-2R expression. However, culture of isolated CD4+ T cells
      with immobilized anti-CD3 mAb plus rIL-2 resulted in a marked proliferation (500
      fold increase in 14 days) of CD4+ T cells. The proliferating CD4+ T cells
      produced IL-2 (92 U/ml) and showed strong cytotoxicity against OKT3 hybridoma
      cells and Daudi, K562, and U937 tumor cells in an anti-CD3 mAb-dependent manner.
      The CD4+ T cells contained significant amounts of cytolytic granule-related
      proteins such as serine esterase and perforin. Activated CD4+ helper/killer cells
      can be generated from both healthy donors and tumor patients and can be
      propagated in vitro for 14 to 35 days by biweekly restimulation with immobilized
      anti-CD3 mAb plus rIL-2. This culture yielded about 20,000-fold increase in cell
      number after a 21-day culture. Bispecific antibody containing anti-CD3 and anti
      glioma Fab components enhanced the cytotoxicity of activated CD4+ helper/killer
      cells against IMR32 glioma cells. Moreover, the activated CD4+ helper/killer
      cells showed both helper and antitumor activity in vivo and prevented growth of
      anti-CD3 hybridoma cells in nude mice whether or not IL-2 was administered. These
      results indicate that anti-CD3 mAb plus IL-2-activated CD4+ helper/killer cells
      may provide an effective strategy for adoptive tumor immunotherapy of cancer.

PMID- 1345788
TI  - Impairment of lymphocyte adhesion to cultured fibroblasts and endothelial cells
      by gamma-irradiation.
AB  - A critical component of immune responsiveness is the localization of effector
      cells at sites of inflammatory lesions. Adhesive molecules that may play a role
      in this process have been described on the surfaces of both lymphocytes and
      connective tissue cells. Adhesive interactions of T lymphocytes with fibroblasts
      or endothelial cells can be inhibited by preincubation of the fibroblasts or
      endothelial cells with antibody to intercellular adhesion molecule 1 (CD54) or by
      preincubation of the T cells with antibody to lymphocyte function-associated Ag 1
      (CD11a/CD18), molecules shown to be important in several other cell-cell adhesive
      interactions. Here we show that gamma-irradiation of human T lymphocytes impaired
      their ability to adhere to both fibroblasts and endothelial cells. This
      impairment was not associated with a loss of cell viability or of cell surface
      lymphocyte function-associated Ag 1 expression. gamma-Irradiation of T cells is
      known to result in the activation of ADP-ribosyltransferase, an enzyme involved
      in DNA strand-break repair, causing subsequent depletion of cellular nicotinamide
      adenine dinucleotide (NAD) pools by increasing NAD consumption for poly(ADP
      ribose) formation. Preincubation of T cells with either nicotinamide or benzamide
      [corrected], both known inhibitors of ADP-ribosyltransferase, completely reversed
      the suppressive effects of gamma-irradiation on T cell adhesion. The maintenance
      of adhesion was accompanied by inhibition of irradiation-induced depletion of
      cellular NAD. These experiments suggest that the impairment of cellular immune
      function after irradiation in vivo may be caused, in part, by defective T cell
      emigration and localization at inflammatory sites.

PMID- 1345789
TI  - Central role for TCR/CD3 ligation in the differentiation of CD4+ T cells toward A
      Th1 or Th2 functional phenotype.
AB  - Activated CD4+ T cells can be classified into distinct subsets; the most
      divergent among them may be considered to be the IL-2 and IFN-gamma-producing Th1
      clones and the IL-4 and IL-5-producing Th2 clones. Because Th1 and Th2 clones can
      usually be detected only after several months of culture, we used conditions that
      modulate the IL-2 and IL-4 production in short term culture. Here we show that
      freshly isolated and subsequently in vitro-activated CD4+ T cells that were
      cultured for 11 days with rIL-2 and restimulated showed a IFN-gamma+ IL-2+ IL-3+
      IL-4- IL-5- pattern. Because these cells were not capable of providing B cell
      help for IgG1, IgG2a, or IgE in an APC- and TCR-dependent T-B cell assay, they
      expressed a phenotype typical for most Th1 clones. In contrast, activated T cells
      that were cultured for 11 days with IL-2 plus a mAb to CD3 and then restimulated
      produced a IFN-gamma- IL-2- IL-3+ IL-4+ IL-5+ pattern. These cells were capable
      of providing B cell help for IgG1, IgG2a, and IgE synthesis and thus presented a
      phenotype typical for Th2 clones. Similar results were observed when mitogenic
      mAb to Thy-1.2 or to framework determinants of the alpha beta TCR were used. The
      induction of Th1- and Th2-like cells did not depend on the relative expression of
      CD44 or CD45 by the T cells before activation in vitro. Because the incubation of
      activated T cells with anti-CD3/TCR mAb induced high unrestricted lymphokine
      production, the latter might be responsible for the Th2-like lymphokine pattern
      observed after restimulation. To address this point, TCR V beta 8+ and V beta 8-
      T cell blasts were co-cultured in the presence of mAb to V beta 8. After
      restimulation, V beta 8+ cells had a IL-4high IL-2low phenotype and V beta 8-
      cells had a IL-4low IL-2high phenotype. This demonstrates that TCR ligation but
      not lymphokines alone are capable of inducing Th2-like cells, and this points out
      a central role for the TCR in the generation of T cell subsets.

PMID- 1345790
TI  - Multiple cytolytic mechanisms displayed by activated human peripheral blood T
      cell subsets.
AB  - It has been proposed that CTL-mediated cytotoxicity may involve multiple lytic
      mechanisms. We have examined both the antibody-redirected cytolytic potential and
      the direct cytotoxicity of purified human peripheral blood high buoyant density
      CD4+ and CD8+ T cells activated with IL-2 and anti-CD3 mAb. TNF-sensitive and TNF
      resistant targets and various metabolic inhibitors were used to compare the
      antibody-redirected cytotoxicity of T cell subsets and discern the role of
      potential lytic mediators. In a 4-h assay against several different nitrophenyl
      modified targets, the heteroconjugated antibody (anti-CD3-anti-nitrophenyl)
      redirected cytolytic potential of 72-h activated CD4+ T cells was inhibited by
      the continuous presence of actinomycin D, cycloheximide, and EGTA, but not
      mitomycin C, cyclosporin A, or cholera toxin (CT). Conversely, only CT and EGTA
      inhibited the antibody-redirected cytolytic potential of activated CD8+ T cells.
      Despite both CD4+ and CD8+ T cell subsets expressing granzymes, pore-forming
      protein, TNF-beta, and TNF-alpha, these T cell subsets displayed distinct
      pathways of antibody-redirected lysis against TNF-sensitive and TNF-resistant
      targets, even in the presence of anti-TNF antibodies. In addition, these same
      effector T cell subsets were also directly cytotoxic (in the absence of
      heteroconjugated antibody) against TNF-sensitive targets in an 18-h assay.
      Indeed, this direct cytotoxicity was completely abrogated by anti-TNF-alpha
      antibody and was sensitive to the metabolic inhibitors (cyclosporin A, CT,
      cycloheximide, and actinomycin D), all of which blocked CD4+/CD8+ T cell TNF
      alpha production. Therefore, both CD4+ and CD8+ T cells were demonstrated to
      utilize antibody and lymphokine-mediated lytic mechanisms. CD4+ and CD8+ effector
      subsets were demonstrated to lyse the same TNF-sensitive target by these two
      different mechanisms. Although it cannot be excluded that the redirected lytic
      mechanisms of both CD4+ and CD8+ effectors share common elements, it is likely
      that other important events in this cytolytic process are fundamentally distinct
      between these subsets of T cells.

PMID- 1345791
TI  - Expression and function of insulin-like growth factor receptors on anti-CD3
      activated human T lymphocytes.
AB  - The pattern of expression of receptors for insulin-like growth factors (IGF-I and
      IGF-II) and insulin was studied on monocyte-depleted human peripheral blood T
      cells activated via anti-CD3. Binding assays demonstrated the sequential
      appearance of receptors for IGF-I, IGF-II, and insulin on activated T cells. IGF
      IR appeared early, their expression reaching maximum levels at or before the peak
      of cellular proliferation. IGF-IIR expression generally followed that of the IGF
      IR and was more transient, with increases and decreases in expression paralleling
      the rise and decline of cellular proliferation. Insulin receptor expression
      remained low throughout the activation time course. The identity of the IGFR on
      anti-CD3-activated T cells was confirmed in affinity cross-linking experiments.
      These data demonstrated a 135,000 Mr peptide that specifically binds radiolabeled
      IGF-I and corresponds to the alpha subunit of the type I IGF-IR, and a 260,000 Mr
      peptide that specifically binds radiolabeled IGF-II and corresponds to the type
      II IGFR. We have additionally found that IGF-I and IGF-II (in nanomolar
      concentrations) produce as much as a threefold enhancement of T cell
      proliferation early in the activation process, correlating with the early
      appearance of IGF-IR. The effect of both IGF appeared to be mediated through the
      type I receptor, since an antibody (alpha IR3), which blocks binding to the alpha
      subunit of this receptor, inhibited enhancement by up to 83%. Furthermore, we
      have found expression of IGF-IR on T cells after activation to be associated with
      both CD4+ and CD8+ T cell subpopulations. These observations provide a foundation
      for investigating the contribution of IGF in regulating T cell proliferation,
      differentiation, and effector function.

PMID- 1345792
TI  - Mechanisms of IFN-gamma induction by natural killer cell stimulatory factor
      (NKSF/IL-12). Role of transcription and mRNA stability in the synergistic
      interaction between NKSF and IL-2.
AB  - We have investigated the molecular mechanisms regulating IFN-gamma production in
      human T lymphocytes stimulated by NK cell stimulatory factor (NKSF/IL-12). We
      show that NKSF synergizes with IL-2 and phorbol diesters inducing the
      accumulation of IFN-gamma mRNA in PHA-activated T cell blasts. NKSF regulates IFN
      gamma mRNA expression in PHA blasts and the T leukemia cell line, TALL-103/2, at
      both the transcriptional and posttranscriptional levels. NKSF increases the
      transcriptional rate for IFN-gamma in both these cell types, as determined by
      nuclear run-on analysis. However, synergy between NKSF and IL-2 can be
      demonstrated only at the level of mRNA stability, and both cytokines are required
      to increase IFN-gamma mRNA half-life.

PMID- 1345793
TI  - Mother-to-infant vertical transmission and cross-colonization of Streptococcus
      pyogenes confirmed by DNA restriction fragment length polymorphism analysis.
AB  - Restriction fragment length polymorphism (RFLP) analysis of total DNA and of
      ribosomal DNA (rDNA) regions (ribotyping) were used to document Streptococcus
      pyogenes vertical mother-to-infant transmission and to investigate the spread of
      S. pyogenes in an obstetric unit. Two isolates from a newborn, two isolates from
      his mother (patient 1), and two isolates from two other mothers (patients 2 and
      3) were studied. RFLP of total DNA, both after HindIII and PvuII digestions and
      ethidium bromide staining, gave indistinguishable patterns for the strains
      isolated from the neonate, his mother, and patient 2. Strains from patient 3 and
      six unrelated strains studied for comparison showed different patterns. In our
      system, ribotyping was less discriminative than total DNA RFLP analysis. DNA RFLP
      analysis therefore provides a valuable molecular tool for studying S. pyogenes
      epidemiology.

PMID- 1345794
TI  - Absence of infectious human immunodeficiency virus type 1 in "natural" eccrine
      sweat.
AB  - Although human immunodeficiency virus type 1 (HIV-1) has been found in numerous
      body fluids, there are no reports of attempts to demonstrate this virus in
      eccrine sweat, a fluid frequently encountered during person-to-person
      interactions. "Natural" eccrine sweat samples and blood from 50 HIV-1
      seropositive patients and 2 HIV-1-seronegative controls were cultured for HIV-1
      by a cocultivation method. Polymerase chain reaction for HIV-1 RNA and proviral
      DNA was done on 40 sweat samples (39 patients, 1 control). HIV-1 was isolated
      from peripheral blood mononuclear cells of 39 (78%) of 50 patients but from none
      of 52 sweat samples. No HIV-1 viral DNA or RNA was detected in the 40 sweat
      samples tested. With present methodology, infectious HIV-1 cannot be demonstrated
      in "natural" eccrine sweat samples from HIV-infected patients.

PMID- 1345795
TI  - Abnormalities of morning serum cortisol levels and circadian rhythms of CD4+
      lymphocyte counts in human immunodeficiency virus type 1-infected adult patients.

PMID- 1345796
TI  - The effect of sulfasalazine on bovine endothelial cell proliferation and cell
      cycle phase distribution. Comparison with olsalazine, 5-aminosalicylic acid, and
      sulfapyridine.
AB  - Sulfasalazine is used in the treatment of chronic inflammatory states, for
      example, in inflammatory bowel disease and to a lesser degree in rheumatoid
      arthritis. In chronic inflammation, the formation of new blood vessels may play a
      key role in maintaining the inflammatory state. This process is dependent on the
      activation and proliferation of the endothelial cells. To investigate the
      possible role of sulfasalazine and its metabolites, sulfapyridine and 5
      aminosalicylic acid, we examined the effect of these drugs on vascular
      endothelial cell proliferation in vitro. Cultures of bovine aortic endothelial
      cells were incubated with sulfasalazine and its metabolites. At 24 hours of
      incubation, sulfasalazine inhibited tritiated thymidine incorporation and cell
      proliferation and had already slowed S-phase progression at a concentration
      greater than 0.125 mmol/L. After 3 hours of incubation, sulfasalazine inhibition
      of tritiated thymidine incorporation into the DNA of endothelial cells was
      observed. This inhibition was completely reversible 24 hours after the drug was
      removed. One of the possible mechanisms for the inhibition of endothelial cell
      proliferation is interference with the de novo synthesis of thymidine that
      depends on folate-dependent enzymes. The effect of deoxyuridine and
      tetrahydrofolate on tritiated thymidine incorporation into cellular DNA, as well
      as release of tritium to water by [5-3H]-labeled deoxyuridine on methylation to
      thymidine, were used as probes for the de novo synthesis of thymidine.
      Deoxyuridine and tetrahydrofolate, when added to cells either individually or
      together for 3 hours, suppressed incorporation of tritiated thymidine into DNA
      through an increase in de novo thymidine synthesis. Sulfasalazine, but not its
      metabolites, reduced this suppression.2+ culture is inhibited by sulfasalazine
      and olsalazine but not by their metabolites. This inhibition appears to depend
      partly on the reduction of de novo synthesis of thymidine that is folate
      dependent.

PMID- 1345797
TI  - Pain, opioid use, and survival in hospitalized patients with advanced cancer.
AB  - PURPOSE: Pain is a common and feared symptom for patients with incurable cancer.
      Comprehensive assessment provides the foundation for effective pain management,
      and data that clarify the relationship between pain and other relevant factors
      also facilitate this process. The main objective of the study was to develop a
      clinical data base for advanced cancer patients and to survey data to determine
      (1) pain severity at admission, (2) opioid use at admission, (3) change in opioid
      use during the hospital stay, and (4) survival in the hospital. PATIENTS AND
      METHODS: Information was collected prospectively on 1,103 patients admitted and
      on 1,017 patients who died within 6 months of the study's end. Demographic and
      clinical data were recorded 72 hours after admission and soon after death or
      discharge. RESULTS: Seventy-three percent of patients had pain at admission.
      Cancer of the cervix was frequently (68%) associated with severe pain, as were
      prostate (52%) and rectal/sigmoid tumors (49%). Severe pain was more probable in
      those with bone metastasis, those admitted from home, and in those younger than
      55 years of age. The majority (71.7%) of patients had a stable dosing pattern,
      and only 4.2% of the patients required dose increases of at least 10% per day.
      CONCLUSION: This study demonstrated the wide variability in opioid doses
      required. No reliable predictor of opioid requirement was identified, and this
      lack of predictability of cancer pain severity underscores the need for ongoing
      assessment.

PMID- 1345798
TI  - American Society for Parenteral and Enteral Nutrition, 16th clinical congress.
      Program summary and abstracts. January 19-22, 1992, Orlando, FL. Abstracts.

PMID- 1345799
TI  - Mortality in patients with the acquired immunodeficiency syndrome treated with
      either foscarnet or ganciclovir for cytomegalovirus retinitis.
AB  - BACKGROUND AND METHODS: We performed a multicenter, randomized, unblinded
      clinical trial (the Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial)
      designed to compare ganciclovir with foscarnet in the treatment of
      cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome
      (AIDS). Of 234 patients, 127 were randomly assigned to ganciclovir and 107 to
      foscarnet; the study drugs were administered according to a common protocol at
      the 11 participating clinical centers. Antiretroviral therapy (with zidovudine,
      didanosine, or dideoxycytidine) was given as dictated by best medical judgment.
      The patients were followed for the progression of retinitis, visual loss, and
      death. RESULTS: Excess mortality in the ganciclovir group (as compared with the
      foscarnet group) led the Policy and Data Monitoring Board to recommend suspension
      of the treatment protocol 19 months after the trial started. As of that time, 65
      of the patients assigned to ganciclovir had died, as compared with 36 of those
      assigned to foscarnet (51 percent vs. 34 percent, P = 0.007; relative risk, 1.79;
      95 percent confidence interval, 1.17 to 2.73). The median survival was 8.5 months
      in the ganciclovir group and 12.6 months in the foscarnet group. Although the
      patients assigned to ganciclovir received less antiretroviral therapy on average
      than those assigned to foscarnet, the excess mortality could not be explained
      entirely by differences in exposure to antiretroviral drugs. In the forscarnet
      group, the only subgroup of patients identified as having excess mortality were
      those whose renal function was compromised at entry. There was no difference
      between the two treatment groups in the rate of progression of retinitis
      (relative risk, 0.95; P = 0.751). CONCLUSIONS: These results suggest that for
      patients with AIDS, and cytomegalovirus retinitis, treatment with foscarnet
      offers a survival advantage over treatment with ganciclovir, although the
      patients may not tolerate foscarnet as well as ganciclovir.

PMID- 1345800
TI  - An outbreak of tuberculosis with accelerated progression among persons infected
      with the human immunodeficiency virus. An analysis using restriction-fragment
      length polymorphisms.
AB  - BACKGROUND: Tuberculosis typically develops from a reactivation of latent
      infection. Clinical tuberculosis may also arise from a primary infection, and
      this is thought to be more likely in persons infected with the human
      immunodeficiency virus (HIV). However, the relative importance of these two
      pathogenetic mechanisms in this population is unclear. METHODS: Between December
      1990 and April 1991, tuberculosis was diagnosed in 12 residents of a housing
      facility for HIV-infected persons. In the preceding six months, two patients
      being treated for tuberculosis had been admitted to the facility. We investigated
      this outbreak using standard procedures plus analysis of the cultured organisms
      with restriction-fragment-length polymorphisms (RFLPs). RESULTS: Organisms
      isolated from all 11 of the culture-positive residents had similar RFLP patterns,
      whereas the isolates from the 2 patients treated for tuberculosis in the previous
      six months were different strains. This implicated the first of the 12 patients
      with tuberculosis as the source of this outbreak. Among the 30 residents exposed
      to possible infection, active tuberculosis developed in 11 (37 percent), and 4
      others (13 percent) had newly positive tuberculin skin tests. Of 28 staff members
      with possible exposure, at least 6 had positive tuberculin-test reactions, but
      none had tuberculosis. CONCLUSIONS: Newly acquired tuberculous infection in HIV
      infected patients can spread readily and progress rapidly to active disease.
      There should be heightened surveillance for tuberculosis in facilities where HIV
      infected persons live, and investigation of contacts must be undertaken promptly
      and be focused more broadly than is usual.

PMID- 1345801
TI  - Burning of a neonate due to a pulse oximeter: arterial saturation monitoring.

PMID- 1345802
TI  - Retinal microvasculopathy and reduced cerebral blood flow in patients with
      acquired immunodeficiency syndrome.

PMID- 1345803
TI  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to
      autologous hemopoietic stem cell transplantation for lymphoma.
AB  - OBJECTIVE: To determine the hemopoietic effects of recombinant human granulocyte
      macrophage colony-stimulating factor (GM-CSF) in patients having autologous
      hemopoietic stem cell transplantation for Hodgkin or non-Hodgkin lymphoma.
      DESIGN: Placebo or GM-CSF was administered after bone marrow or peripheral blood
      stem cell transplantation or both in a randomized, double-blind phase III trial
      by daily intravenous infusion (10 micrograms/kg body weight) until absolute
      neutrophil counts reached greater than or equal to 1000/mm3 on 3 consecutive
      days. SETTING: Bone marrow transplantation unit in a university hospital.
      PATIENTS: Sixty-nine consecutive patients with Hodgkin or non-Hodgkin lymphoma
      received GM-CSF (36 patients) or placebo (33 patients). MEASUREMENTS AND MAIN
      RESULTS: Patients who received GM-CSF achieved absolute neutrophil counts greater
      than or equal to 500/mm3 (median, 12 compared with 16 days, P = 0.02) and
      absolute neutrophil counts greater than or equal to 1000/mm3 (median, 15 compared
      with 24 days, P less than 0.001) more quickly than patients who received placebo.
      Multivariate analysis indicated that use of GM-CSF, peripheral blood stem cells,
      and unpurged bone marrow were the strongest predictors for early neutrophil
      recovery greater than 500/mm3. Bacterial infections were significantly reduced in
      the GM-CSF group (P = 0.04). Delayed engraftment (neutrophils less than 500/mm3
      at day 30) occurred in 26% and 17% of the placebo and GM-CSF groups,
      respectively, and correlated with the absence of detectable myeloid progenitor
      cells (colony-forming units-granulocyte macrophage, CFU-GM) (P less than 0.001)
      in marrow aspirate specimens obtained on day 15. Time to platelet independence,
      duration of hospital stay, severe adverse reactions, relapse, and disease-free
      survival rates did not differ significantly between the two groups. CONCLUSIONS:
      Administration of GM-CSF after autologous hemopoietic stem cell transplantation
      in patients with lymphoma resulted in accelerated myeloid recovery, particularly
      in patients who received peripheral blood stem cells and nonpurged bone marrow,
      and was associated with a decreased incidence of bacterial infections.

PMID- 1345805
TI  - Arthur Vineberg and the internal mammary artery implantation procedure.
AB  - A summary of Vineberg's experimental pioneer work on the internal mammary artery
      implant is presented, together with comments on the clinical series and the
      difficulty in evaluating the results before the era of coronary angiography. A
      plea is made for recognition of the fact that an implanted internal mammary
      artery can arborize and communicate with the native coronary arteries.

PMID- 1345804
TI  - Effect of internal mammary artery dissection on sternal vascularization.
AB  - Internal mammary artery (IMA) dissection may cause sternal devascularization and
      ischemia resulting in sternal wound complication. To evaluate the effect of
      median sternotomy and IMA dissection on sternal vascular supply, sternal bone
      tomography was performed 7 days and 1 month after cardiac operation in 67
      patients. Seventeen nondiabetic patients had single IMA grafts, 18 had double IMA
      grafts, and 12 had only saphenous vein grafts or valve replacement. Twenty
      diabetic patients were studied after any one of these operations. Seven patients
      were restudied 1 month after the operation. Sternal technetium-99m-methylene
      diphosphate tomography was performed. The sternum was visualized and focal zones
      of hypoactivity represented sternal hypoperfusion. The ratio of hypoactivity area
      over total sternal area was calculated for every patient. After median sternotomy
      without single or double IMA grafts, the averaged hypoperfusion ratio was 4% +/-
      1% compared with 13% +/- 3% after single IMA grafts and 24% +/- 6% after double
      IMA grafts (p less than 0.0001). Diabetic patients without IMA, with single IMA,
      and with double IMAs showed hypoperfusion areas of 5% +/- 3%, 15% +/- 5%, and 23%
      +/- 9%, respectively, a result similar to that of nondiabetic patients. One month
      after operation the hypoperfusion area decreased to 2% +/- 2% (p less than 0.05)
      in restudied patients. Our results indicate that IMA dissection causes a
      significant although partial and temporary sternal ischemia, which is more severe
      after double IMA than single IMA mobilization and which may be incriminated in
      the development of sternal wound infection. This vascularization defect was not
      greater among patients with diabetes mellitus.

PMID- 1345806
TI  - Harvesting of the internal mammary artery and the healing median sternotomy.

PMID- 1345807
TI  - Binding of fluorescein-labeled anaphylatoxin C5a to human peripheral blood,
      spleen, and bone marrow leukocytes.
AB  - The expression of C5a receptors (C5aR) on human leukocytes was evaluated by flow
      cytometry using fluorescein-labeled human C5a (C5a-F). Granulocytes and CD14+
      mononuclear cells (MNL) but not CD3+, CD20+, CD16+, CD56+, or CD11b+ lymphocytes
      in peripheral blood and spleen bound C5a-F. C5a-F binding was saturable and
      inhibitable by anti-C5a monoclonal antibody (MoAb) C17/5 or unlabeled C5a. During
      hemodialysis, which led to the generation of C5a, only granulocytes and monocytes
      increased their expression of the adhesion molecule CD11b (CR3). In vitro, C5a
      induced an increase of CR3 and p 150/95 (CD11c/CR4) only on myeloid cells.
      However, treatment of leukocytes with phorbol 12-myristate 13 acetate increased
      CR3 and CR4 expression on both myeloid cells and a lymphocyte subpopulation.
      Stimulation of MNL in mixed lymphocyte cultures or by treatment with conditioned
      medium or with IFN-gamma did not induce binding sites for C5aR on lymphocytes and
      reduced the binding of C5a-F to monocytes. The expression of C5aR on low-density
      bone marrow cells was analyzed by setting appropriate gates during flow
      cytometry. Cells that bound C5a-F were found in all populations that contained
      granulocyte and monocyte precursors, but not in lymphocyte precursor populations.
      All C5aR+ bone marrow cells were CD34 and expressed high levels of CR3, which
      suggests a late appearance of C5aR during myeloid cell maturation. Our results
      indicate that C5aR is exclusively expressed on myeloid cells within the
      hematopoetic cell population.

PMID- 1345808
TI  - Proliferation-linked regulation of type II IMP dehydrogenase gene in human normal
      lymphocytes and HL-60 leukemic cells.
AB  - Human IMP dehydrogenase (IMPDH; EC 1.1.1.205) was recently found to consist of
      two molecular species (types I and II) with high expression of type II isozyme in
      leukemic cells. Here we report that the low level of type II mRNA in normal
      lymphocytes was up-regulated by phytohemagglutinin stimulation (3.2-fold) and
      Epstein-Barr viral transformation (5.7-fold). The type II mRNA expression in
      quiescent HL-60 cells was also elevated 2.8-fold by serum stimulation. Conversely
      the enhanced level of type II IMPDH mRNA in HL-60 cells was down-regulated to
      less than 5% along with differentiation induced by retinoic acid (1 microM),
      phorbol-12-myristate-13-acetate (33 nM), or dimethyl sulfoxide (1.25%)
      independent of end-stage phenotype. By contrast, type I IMPDH mRNA was expressed
      constitutively in the various states of proliferation and differentiation. The
      type II IMPDH stringently linked with cell proliferation should be a crucial
      target for antileukemic and immunosuppressive chemotherapy.

PMID- 1345809
TI  - Loss of heterozygosity at the human RAP1A/Krev-1 locus is a rare event in
      colorectal tumors.
AB  - Kirsten-ras-revertant-1 (Krev-1/Rap1A) is a recently identified tumor suppressor
      gene which induces flat revertants when introduced into a variety of ras
      transformed cell lines in vitro. Since 47% of colorectal carcinomas have
      transforming mutations in ras protooncogenes, and since Krev-1 is expressed at
      high levels in normal colonic mucosa, we hypothesized that inactivation at the
      Krev-1 locus may be necessary for transformation of colonic cells. Loss of
      heterozygosity is a common method of inactivation of tumor suppressor genes in
      colorectal tumors. Therefore, we analyzed loss of heterozygosity in 52 patients
      with sporadic colorectal cancer. Because Krev-1 had no previously described
      polymorphisms, we first identified a BclI restriction fragment length
      polymorphism which showed 40% heterozygosity in 50 unrelated individuals.
      However, only one tumor from 18 informative patients showed allelic loss at the
      Krev-1 locus. This suggests that loss of heterozygosity is not a common mechanism
      of inactivation at the Krev-1 locus in colorectal cancer. However, the results do
      not exclude a role for Krev-1 in the etiology of this neoplasm because
      inactivation may occur by other mechanisms.

PMID- 1345810
TI  - Mechanism of cross-resistance to a camptothecin analogue (CPT-11) in a human
      ovarian cancer cell line selected by cisplatin.
AB  - We established a cisplatin-resistant human ovarian cancer cell line (HAC2/0.1)
      from the parent cell line (HAC2/P) by continuous exposure of HAC2/P to 0.1
      microgram of cisplatin/ml. Drug sensitivity determined by colony assay revealed
      that HAC2/0.1 was 2.4 times as resistant to cisplatin as the parental cell line.
      HAC2/0.1 was 12.1 and 2.0 times as resistant to (4s)-4,11-diethyl-4-hydroxy-9-[(4
      piperidinopiperidino)-carbony loxy]dione hydrochloride trithydrate (CPT-11) and 7
      ethyl-10-hydroxy-CPT (SN-38; an active metabolite of CPT-11), respectively, than
      HAC2/P. We studied the mechanism of cross-resistance to CPT-11 in HAC2/0.1. The
      glutathione (GSH) content was higher in HAC2/0.1 than in HAC2/P. The activity of
      DNA topoisomerase I and the accumulation of CPT-11 and SN-38 were also the same.
      On the other hand, the conversion of CPT-11 to SN-38 in HAC2/0.1 was about 3-fold
      less than in HAC2/P. Treatment of the parent and resistant cell lines with
      buthionine sulfoxamine (BSO) decreased the GSH content of both cell lines and
      decreased the 50% inhibitory concentrations of all the tested drugs for HAC2/0.1.
      The accumulation of CPT-11 in HAC2/0.1 but not in HAC2/P was increased by BSO
      treatment. On the other hand, in HAC2/P the 50% inhibitory concentrations of SN
      38 and CPT-11 were not influenced by BSO treatment. The 50% inhibitory
      concentration of CPT-11 for HAC2/0.1 was not reduced by BSO treatment to the
      level for HAC2/P, even though the GSH content had been reduced more than in
      HAC2/P. These results show that there is no clear relationship between GSH and
      resistance to CPT-11. The decreased conversion of CPT-11 to SN-38 is considered
      to be the main cause of resistance to CPT-11 in this cell line.

PMID- 1345811
TI  - Molecular and cellular characterization of human renal cell carcinoma cell lines.
AB  - Recent studies have suggested that a tumor suppressor gene located in the region
      3p21-26 of chromosome 3 is essential to the genesis of sporadic renal cell
      carcinoma (RCC) and that other tumor suppressor genes located on other
      chromosomes may be involved with progression of this malignancy. The cellular
      heterogeneity of solid tumors complicates their analysis. In order to analyze a
      homogeneous population of tumor cells and identify genetic changes associated
      with histology in renal cortical tumors, we have established and characterized 35
      RCC lines derived from tumor tissue from 31 patients with renal cell carcinomas.
      The overall success rate in establishing these cell lines from fresh or frozen
      specimens was 75% (18 of 24) and 35% (17 of 48), respectively. These lines
      differed in their morphology, growth rates, and tumorigenicity in athymic nude
      mice. Molecular characterization utilizing DNA fingerprinting and restriction
      fragment length polymorphism deletion analysis was performed to detect somatic
      mutations and loss of heterozygosity on the short arm of chromosome 3. Analysis
      revealed loss of heterozygosity on chromosome 3p in 25 cell lines derived from 28
      informative nonpapillary forms of RCC (89%). Deletion-mapping analysis showed the
      retention of the distal locus, D3S18, in one of the RCC cell lines, which further
      localized the position of the putative tumor suppressor gene to the region
      proximal to D3S18. Although deletions on chromosome 3 have been recently
      suggested to be specific to the clear cell-type phenotype, our results revealed
      no correlation between loss of heterozygosity and clear or granular cell types.

PMID- 1345812
TI  - Pheochromocytomas and C-cell thyroid neoplasms in transgenic c-mos mice: a model
      for the human multiple endocrine neoplasia type 2 syndrome.
AB  - Transgenic mice carrying and expressing a mos protooncogene, linked to the
      Moloney murine sarcoma virus long terminal repeat, develop severe neurological
      defects and lens abnormalities. Here we report that after long latent periods,
      mice in three of four of these mos transgenic lines develop a high frequency of
      multicentric pheochromocytomas and/or medullary thyroid neoplasms. The pattern of
      tumor formation is remarkably similar to the human autosomal dominantly inherited
      neoplastic syndrome, multiple endocrine neoplasia type 2 (MEN 2), and tumors from
      these transgenic animals display the same neuroendocrine marker staining pattern
      as seen in MEN 2. The similarity between the tumor pathologies and presentation
      patterns of MEN 2 patients and mos transgenic mice suggests that they may arise
      through related pathways. The type of tumor presentation varies in a line
      dependent manner indicating that there is interaction between the transgene and
      the genetic background. Moreover, when the non-tumor-bearing mos transgenic line
      is crossed to a different mouse background, the F1 offspring display the MEN 2
      phenotype. These studies indicate that penetrance of the autosomal dominant mos
      transgenic phenotype is dependent on both integration site and background.

PMID- 1345813
TI  - Leukoregulin and gamma-interferon inhibit human papillomavirus type 16 gene
      transcription in human papillomavirus-immortalized human cervical cells.
AB  - The human papillomavirus (HPV) transforming genes E6 and E7 are retained and
      expressed in the majority of cervical cancers implying an important role for
      these proteins in maintenance of the malignant phenotype. Leukoregulin (LR) and
      recombinant gamma-interferon (r-IFN-gamma), lymphokines secreted by immune cells
      present in regressing HPV infections, inhibited transcription of E6/E7 RNAs in
      several human cervical epithelial cell lines immortalized by recombinant HPV-16, 
      18, and -33 DNAs. r-IFN alpha was not effective. Reduction in E6/E7 RNA
      expression was accompanied by inhibition of cell proliferation coincident with an
      increase in epidermal transglutaminase activity, a marker of squamous
      differentiation. LR and r-IFN gamma enhanced transcription of class 1 cell
      surface histocompatibility antigens (HLA) and r-IFN gamma additionally induced
      HLA class 2 expression. HPV-immortalized cells developed partial resistance to
      the growth inhibitory effects of lymphokines after malignant transformation or
      extended propagation in culture. This is the first demonstration that LR and r
      IFN gamma selectively inhibit transcription of HPV-transforming genes and
      suggests a molecular mechanism by which these lymphokines participate in
      regression of premalignant cells.

PMID- 1345814
TI  - Effect of protein tyrosine phosphatase 1B expression on transformation by the
      human neu oncogene.
AB  - Many oncogenes encode proteins with a tyrosine kinase activity that appears to be
      directly involved in the process of transformation. Because these kinases are
      themselves activated for transformation by tyrosine phosphorylation, proteins
      which remove phosphate from tyrosine residues, protein tyrosine phosphatases
      (also termed phosphotyrosine phosphatases and protein phosphotyrosyl
      phosphatases), are intuitive candidate transformation suppressors. The human
      PTP1B gene, previously cloned in our laboratory and encoding the low molecular
      weight protein tyrosine phosphatase PTPase 1B, was introduced into NIH 3T3 cells.
      Subsequent transformation of these PTPase 1B-expressing cells by an oncogenic
      form of the human neu gene was suppressed relative to control NIH 3T3 cells. This
      suppression of transformation was observed in assays for focus formation,
      anchorage-independent growth, and tumorigenicity. Tumorigenicity assays indicated
      a complex effect of PTPase 1B expression on transformation.

PMID- 1345815
TI  - The role of beta-adrenergic blocking agents in preventing sudden cardiac death.
AB  - The failure of encainide and flecainide to reduce mortality after infarction in
      the Cardiac Arrhythmia Suppression Trial and the failure of low-dose amiodarone
      to prevent sudden cardiac death in patients with a low left ventricular ejection
      fraction has shifted attention to other strategies, such as beta-adrenergic
      blocking agents, to prevent sudden cardiac death. Evidence suggesting that beta
      adrenergic blocking agents might be useful, especially in patients with low left
      ventricular ejection fraction, is accumulating. Previous data from studies using
      beta-adrenergic blocking agents and the mechanisms by which beta-adrenergic
      blocking agents might be of value in preventing sudden cardiac death are
      reviewed. These considerations and the availability of new investigational beta
      adrenergic blocking agents with vasodilator properties provide a new opportunity
      to test the hypothesis that beta-adrenergic blocking agents are useful in
      preventing sudden cardiac death, especially in patients with a low left
      ventricular ejection fraction.

PMID- 1345816
TI  - Clinical features of the idiopathic long QT syndrome.
AB  - Long QT syndrome (LQTS) is an infrequently occurring familial disorder in which
      affected members have electrocardiographic QT interval prolongation and a
      propensity to syncope and fatal ventricular arrhythmias. This review of the
      current literature includes discussions of inheritance, clinical presentation,
      diagnosis, and treatment of LQTS. At present, there are three modalities of
      treatment for LQTS patients: beta-blockers, pacemakers, and left cervicothoracic
      sympathetic ganglionectomy. Because the clinical course of LQTS is quite
      variable, therapy must be individualized for each patient.

PMID- 1345817
TI  - Effect of small doses of somatostatin analog, octreotide, on gallbladder
      contractility in normal Chinese adults.
AB  - The acute effects of single different doses of the somatostatin analog octreotide
      on the contractility of the gallbladder stimulated by fatty meal were studied in
      six healthy Chinese volunteers. Gallbladder contraction after a fatty meal was
      significantly suppressed by octreotide at doses of 50, 25, 12.5, and 5
      micrograms. Mean duration of suppression lasted for more than 10 hr at doses of
      25 and 50 micrograms, after which the gallbladder contractility was restored at
      24 hr in three and four, respectively, of the six subjects. The percentage of
      relative gallbladder contraction (PRGC) in all subjects receiving 12.5 and 5
      micrograms octreotide returned to pretreatment values at 10 hr but had not
      returned to normal 6 hr after the injection of 5 micrograms octreotide. In
      summary, octreotide inhibits the contraction of the gallbladder even with a dose
      as low as 5 micrograms. It appears that it may not be possible to avoid
      gallbladder dysfunction during long-term octreotide therapy by decreasing the
      dose. Further studies including modalities to increase the contractility of the
      gallbladder are recommended.

PMID- 1345818
TI  - First Conference on Biological Replacement in Sensory Systems. St. Louis,
      Missouri, March 15-17, 1991.

PMID- 1345819
TI  - Development of olfactory marker protein and tyrosine hydroxylase immunoreactivity
      in the transplanted rat olfactory bulb.
AB  - Evidence suggests that tyrosine hydroxylase (TH) expression by juxtaglomerular
      (JG) neurons of the olfactory bulb (OB) is dependent upon input from primary
      olfactory neurons (ONs), which are identifiable using immunocytochemical
      localization (ICC-L) methods for olfactory marker protein (OMP). When the input
      from the continuously regenerating ONs is temporarily removed (either surgically
      or chemically), JG cells cease TH production until ON contact is reestablished.
      We are studying this transneuronal regulation using the rat OB in a
      transplantation (TX) model. Fetal OBs, labeled in utero with tritiated thymidine,
      were transplanted (TX) into a site vacated by removal of a neonatal host OB. Host
      animals were sacrificed at varying periods after TX. Alternate sets of frozen
      sections were then processed for autoradiography or using ICC-L for TH and OMP.
      As early as 1 week post-TX, OMP-positive fibers and glomerulus-like structures
      were seen throughout the TX OB. Despite this extensive and rapid OMP
      reinnervation, TH expression returned very slowly and the number of TH expressing
      cells never approached control levels. The reduced TH activity in TXs may be due
      to failure of JG cells to survive or to develop the correct phenotype under TX
      conditions. Alternatively, input from ON fibers may only be necessary, but not
      sufficient, for the expression of TH.

PMID- 1345820
TI  - Comparative biological responses of rabbits infected with human T-lymphotropic
      virus type I isolates from patients with lymphoproliferative and
      neurodegenerative disease.
AB  - An experimental rabbit model was used to determine host responses to infection by
      various human T-lymphotropic virus type-I (HTLV-I) strains. Seven groups of 4 to
      5 rabbits each were inoculated with lethally-irradiated HTLV-I-infected cell
      lines derived from patients with adult T-cell leukemia/lymphoma or from patients
      with HTLV-I-associated myelopathy. Four separate control groups of 2 rabbits each
      were inoculated with similarly prepared HTLV-I-negative cells derived from
      rabbits or humans. Anti-viral antibody responses were assessed by immunoblot
      assay and hematologic parameters were measured using automated cell counters and
      cytologic staining. The virologic status of challenged rabbits was determined by
      co-culture and HTLV-I antigen capture assay, as well as by polymerase chain
      reaction (PCR) amplification of HTLV-I DNA from peripheral blood mononuclear
      cells (PBMC) or tissues. The HTLV-I inocula could be separated into groups based
      upon their infectivity to rabbits: highly infectious strains elicited intense
      serologic responses and were detected frequently in tissues by antigen and PCR
      assays, while other strains were moderately to poorly infectious, induced weak
      antibody responses and were infrequently detected by antigen and PCR assays.
      Overall, PBMC appeared to have the greatest quantity of HTLV-I containing cells,
      while bone marrow was a poor source of virus. No clinical or hematologic
      abnormalities were evident during the 24-week course of infection. Taken
      together, our results suggest there is heterogeneity in the biological response
      to HTLV-I infection which is, in part, dependent on the infecting strain of
      virus.

PMID- 1345821
TI  - Dipeptidyl peptidase IV expression identifies a functional sub-population of
      breast fibroblasts.
AB  - The immunocytochemical distribution of the cell-surface enzyme dipeptidyl
      peptidase IV (DPP IV) has been studied in the human breast at the light and
      ultrastructural level. The presence of the enzyme was demonstrated on the cell
      membranes of interlobular fibroblasts, whilst intralobular fibroblasts were DPP
      IV-negative. A fluorograph, after immunoprecipitation of 35S-methionine-labelled
      proteins of fibroblasts from primary breast cultures with an anti-serum to DPP
      IV, demonstrated a band at 135 kDa consistent with the presence of the enzyme.
      The clear delineation of 2 functionally distinct subpopulations of breast
      fibroblasts was maintained in benign fibro-adenomas and cystosarcoma phyllodes,
      both tumour types having growth characteristics of intralobular stroma. This
      observation has important implications for both normal breast biology and for
      breast carcinogenesis.

PMID- 1345822
TI  - Association between restriction fragment length polymorphism of the L-myc gene
      and lung metastasis in human breast cancer.
AB  - EcoRI restriction fragment length polymorphism (RFLP) of the L-myc gene was
      examined in leukocyte DNAs isolated from 381 breast cancer patients. No
      differences in the patterns of L-myc RFLP were found between breast cancer
      patients and healthy individuals. However, among 97 patients who relapsed, a
      statistical correlation was found between L-myc RFLP and lung metastases (p less
      than 0.05). These results are in close agreement with previous findings in
      patients with cancer of the lung, bone or kidney, and suggest that L-myc RFLP may
      be a useful marker for predicting lung metastasis in some human cancers.

PMID- 1345823
TI  - Th1 lymphokine production profiles of nickel-specific CD4+T-lymphocyte clones
      from nickel contact allergic and non-allergic individuals.
AB  - Panels of nickel-specific T-lymphocyte clones (TLC) were prepared from nickel
      allergic and non-allergic donors. TLC from both panels showed similar levels of
      expression of TCR alpha/beta, CD4, CD2, CD25, and CD29 and recognized nickel in
      association with class II HLA molecules with restriction determinants in HLA-DR,
      HLA-DP, and HLA-DQ. The lymphokine secretion was analyzed in TLC from both panels
      upon antigen-specific or non-specific stimulation and was compared with the
      secretion profiles of representants of pre-established human atopen-specific Th1
      and Th2 cells. Nickel-specific TLC from both panels showed a lymphokine secretion
      pattern similar to the atopen-specific Th1 cells, although there was some
      variation from clone to clone. Most TLC secreted substantial amounts of IFN
      gamma, IL-2, TNF-alpha, and GM-CSF, but little or no IL-4 and IL-5. The variation
      observed mainly concerned IL-2 secretion that could be low or absent in some of
      the TLC. The general secretion pattern did not change upon different modes of
      stimulation, including activation via CD3, CD2, or CD28. Because nickel-specific
      TLC from allergic and non-allergic individuals show a similar Th1 secretion
      pattern, the present results give no evidence that aberrant lymphokine secretion
      by CD4+T cells determines the contact allergic state, as was found for atopic
      allergy in a previous study.

PMID- 1345824
TI  - Keratinocyte activation following T-lymphocyte binding.
AB  - T lymphocytes infiltrate the epidermis and follicular epithelium adhering to
      keratinocytes within hours following induction of cutaneous inflammation. To
      determine if the physical binding interaction between a T cell and keratinocyte
      induces transmission of activation pathways, CD3+ T cells (HUT 78) were allowed
      to directly bind to non-cytokine-treated cultured keratinocytes. When these T
      cells bound to keratinocytes, the keratinocytes were activated as evidenced by
      detection of tumor necrosis factor-alpha, interleukin-6, and intercellular
      adhesion molecule-1 mRNA. This induction was relatively mRNA specific, as several
      other mRNA were not found to be altered. This activation process appeared to be
      one-sided, as no change in HUT cell mRNA levels was detectable. The keratinocyte
      activation process was confined to cultures that had direct physical binding by
      HUT cells, because co-culturing the HUT cells immediately above the keratinocyte
      monolayer (but not in direct contact), resulted in no such mRNA alterations. This
      direct adhesion-mediated activation of keratinocytes by T lymphocytes may be
      important in the genesis of cutaneous inflammation by amplifying the original
      stimulus, as well as contributing to the trafficking pattern of inflammatory
      cells as they leave the general circulation and enter the skin.

PMID- 1345825
TI  - Barrett's ulcer: a surgical disease?
AB  - Between 1973 and 1990, 285 patients with Barrett's esophagus were treated at the
      Lahey Clinic. Of these patients, 73 had adenocarcinoma in Barrett's esophagus
      either when first seen or while under surveillance. Of the remaining 212 patients
      with benign Barrett's esophagus, 30 had endoscopic evidence of a Barrett's ulcer,
      for a prevalence of 14%. Initial treatment consisted of aggressive medical
      therapy, including H2 antagonists and antacids as well as the usual dietary and
      antireflux measures. In 2 to 4 months, 27 patients underwent repeat endoscopy.
      Continued endoscopic evaluation in this group totaled 109 patient-years, with a
      range of 2 months to 13 years (median 2.3 years). Complete healing occurred in 23
      of the 27 patients (85%) in 2 to 14 months (median 4 months). Recurrent ulcers
      developed in seven patients, and these ulcers healed with further medical therapy
      in five patients. Antireflux procedures were performed in four of six patients
      with nonhealing Barrett's ulcers, 1 to 1.5 cm in size, and all healed. Two
      patients refused to have an operation. In our experience, the majority of
      Barrett's ulcers heal with medical therapy. We reserve surgical intervention for
      otherwise suitable candidates for operation when no evidence of healing is found
      within 4 months of medical therapy or for the complications of Barrett's ulcer,
      namely, perforation, uncontrollable hemorrhage, or malignant degeneration, which
      were not encountered in this series.

PMID- 1345826
TI  - Influence of catheter type on occurrence of thrombophlebitis during peripheral
      intravenous nutrition.
AB  - To reduce the likelihood of thrombophlebitis during intravenous feeding through a
      peripheral vein, the osmolality of the solution is usually reduced by
      disproportionately raising the lipid content and lowering the carbohydrate,
      electrolyte, and aminoacid concentrations. The possibility that delivery system
      rather than feed is the main influence on the development of thrombophlebitis was
      examined in a randomised comparison of a fine-bore silicone catheter against a
      short 'Teflon' cannula. The nutrient solution given through a peripheral vein was
      a standard feed used for infusion into a central vein (osmolality 1250 mOsmol/kg,
      13 g nitrogen, 200 g glucose [800 kcal], and lipid emulsion [1000 kcal]). 27
      patients received the infusion through a fine-bore silicone rubber catheter
      (diameter 23 G, length 15 cm) and 23 through a teflon catheter (diameter 20 G,
      length 3.2 cm). The median duration of feeding was 5 days in each of the two
      groups. Thrombophlebitis developed in all patients in the teflon group but in
      only 2 (7%) of the silicone group. The first silicone catheter for a patient
      lasted a median of 128.5 h, compared with 40 h for the first teflon cannula (p
      less than 0.001). The results show that when a nutrient solution of osmolality
      1250 mOsmol/kg is delivered through a peripheral vein with an ultrafine-bore
      silicone catheter, the risk of thrombophlebitis is low. For many patients
      intravenous feeding may thus be given through a peripheral instead of a central
      vein without compromising the nutritional adequacy of the feed.

PMID- 1345827
TI  - Cerebromeningeal haemophagocytic lymphohistiocytosis.
AB  - We describe 3 children with a progressive encephalopathy that was characterised
      by irritability, convulsions, cranial nerve palsies, ataxia, nystagmus, walking
      difficulties, delayed psychomotor development, hemiplegia/tetraplegia, visual
      disturbance, vomiting, neck stiffness, and non-specific signs of raised
      intracranial pressure. A final diagnosis was made in all 3 patients from necropsy
      material. The clinical features were ascribed to multiple inflammatory,
      predominantly lymphocytic, reactions and raised intracranial pressure. This
      condition is an atypical form of haemophagocytic lymphohistiocytosis, which
      normally presents with fever, hepatosplenomegaly, and cytopenias. By contrast,
      the disease pattern in our 3 children was dominated by cerebromeningeal
      involvement, which can precede the typical systemic symptoms of haemophagocytic
      lymphohistiocytosis. An awareness of this condition is important because
      treatments are available.

PMID- 1345828
TI  - Parvovirus B19 outbreak in a children's ward.
AB  - Parvovirus B19 infection can cause severe complications in pregnant women,
      individuals with haemolytic anaemia, and those who are immunocompromised. In a
      hospital outbreak of this infection, a balance should be struck between
      protection of these individuals and the maintenance of medical services. The
      index case of an outbreak of parvovirus B19 infection among staff and patients of
      a paediatric ward was not identified. 58 members of staff were screened for B19
      markers and 4 of the 6 susceptible men and 6 of the 24 susceptible women became
      infected (p = 0.05) as defined by serum IgM and viraemia. 1 of the 11 adults (10
      members of staff and 1 parent) infected remained symptom-free. 12
      immunocompromised patients were also assessed, and symptom-free infection
      developed in 2 of these. During the outbreak staff with symptoms were put on sick
      leave, immunocompromised patients (there were none with haemolytic anaemia) were
      given normal human immunoglobulin and nursed in single rooms by B19 IgG-positive,
      IgM-negative staff, and the ward was closed to B19 IgG-negative pregnant women.
      However, the limitation of spread of infection cannot be attributed with
      certainty to the measures taken.

PMID- 1345829
TI  - Trained overseas, unable to return home: plight of doctors from developing
      countries.

PMID- 1345830
TI  - Fickle politics of health-care discontent.

PMID- 1345831
TI  - Budd-Chiari syndrome.

PMID- 1345832
TI  - Anaesthesia awareness: an orthopaedic case.

PMID- 1345833
TI  - Activity of influenza vaccine against virus strains now circulating.

PMID- 1345834
TI  - Mood and peak flow in asthma.

PMID- 1345835
TI  - Substitution therapy for C1 esterase deficiency.

PMID- 1345836
TI  - Prenatal diagnosis of sporadic neurofibromatosis 1.

PMID- 1345837
TI  - Prophylactic platelet transfusion in acute leukaemia.

PMID- 1345838
TI  - D-dimer as therapeutic and diagnostic aid in pulmonary embolism.

PMID- 1345839
TI  - Haemoperitoneum induced by fine-needle aspiration of liver in patients with
      disseminated intravascular coagulation.

PMID- 1345840
TI  - Gestational age and obstetric performance.

PMID- 1345841
TI  - Gestational age and obstetric performance.

PMID- 1345842
TI  - Gestational age and obstetric performance.

PMID- 1345843
TI  - Gestational age and obstetric performance.

PMID- 1345844
TI  - Laparoscopically assisted vaginal hysterectomy.

PMID- 1345845
TI  - Laparoscopically assisted vaginal hysterectomy.

PMID- 1345846
TI  - Liver failure due to recombinant alpha interferon for chronic myelogenous
      leukaemia.

PMID- 1345847
TI  - Acute cerebral artery occlusion and thrombolytic therapy.

PMID- 1345848
TI  - Magnetic resonance angiography and use of contrast agents.

PMID- 1345849
TI  - Renal failure 22 years after kidney donation.

PMID- 1345850
TI  - Intrafamilial spread of hepatitis A.

PMID- 1345851
TI  - Subtyping meningococci.

PMID- 1345852
TI  - Health crisis in African countries.

PMID- 1345853
TI  - Sick building syndrome.

PMID- 1345854
TI  - N-acetylcysteine and lipoprotein(a)

PMID- 1345855
TI  - Dural prostheses, where do we go from here?

PMID- 1345856
TI  - Spontaneous abortion and exposure to vinyl chloride.

PMID- 1345857
TI  - Morbidity after breast biopsy for benign disease in a screened population.

PMID- 1345858
TI  - Chagas' disease in Peruvian Inca mummy.

PMID- 1345859
TI  - Tropical ulcers after sports injuries.

PMID- 1345860
TI  - Determinants of HIV disease progression.

PMID- 1345861
TI  - Reducing HIV transmission by seronegative blood.

PMID- 1345862
TI  - In-vitro activity of zidovudine against mycoplasma.

PMID- 1345863
TI  - Screening blood donations for HCV.

PMID- 1345864
TI  - Fetal ductus venosus and its sphincter mechanism.

PMID- 1345865
TI  - Treatment strategies for Alzheimer's disease.

PMID- 1345866
TI  - Prevention of ultraviolet-light-induced herpes labialis.

PMID- 1345867
TI  - Treatment strategies for Alzheimer's disease.

PMID- 1345868
TI  - Carrier status diagnosis in Duchenne muscular dystrophy with "conformational" DNA
      polymorphism.

PMID- 1345869
TI  - Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune
      therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths
      among 75,000 women. Early Breast Cancer Trialists' Collaborative Group.

PMID- 1345870
TI  - Routine ultrasonography in utero and school performance at age 8-9 years.
AB  - Most fetuses in developed countries are exposed in utero to diagnostic ultrasound
      examination. Many pregnant women express concern about whether the procedure
      harms the fetus. Since most routine ultrasound examinations are done at weeks 16
      22, when the fetal brain is developing rapidly, effects on neuronal migration are
      possible. We have sought an association between routine ultrasonography in utero
      and reading and writing skills among children in primary school. At the age of 8
      or 9 years, children of women who had taken part in two randomised, controlled
      trials of routine ultrasonography during pregnancy were followed-up. The women
      had attended the clinics of 60 general practitioners in central Norway during
      1979-81. The analysis of outcome was by intention to treat: 92% of the "screened"
      group had been exposed to ultrasound screening at weeks 16-22, and 95% of
      controls had not been so exposed, but there was some overlap. 2428 singletons
      were eligible for follow-up, and the school performance of 2011 children (83%)
      was assessed by their teachers on a scale of 1-7; the teachers were unaware of
      ultrasound exposure status. A subgroup of 603 children underwent specific tests
      for dyslexia. There were no statistically significant differences between
      children screened with ultrasound and controls in the teacher-reported school
      performance (scores for reading, spelling, arithmetic, or overall performance).
      Results from the dyslexia test sample showed no differences between screened
      children and controls in reading, spelling, and intelligence scores, or in
      discrepancy scores between intelligence and reading or spelling. The test results
      classified 21 of the 309 screened children (7% [95% confidence interval 3-10%])
      and 26 of the 294 controls (9% [4-12%]) as dyslexic. The risk of having poor
      skills in reading and writing was no greater for children whose mothers had been
      offered routine ultrasonography than for those whose mothers had not been offered
      the procedure.

PMID- 1345871
TI  - Tumour necrosis factor alpha in stool as a marker of intestinal inflammation.
AB  - Measurement of disease activity in patients with inflammatory bowel disease is
      difficult. The best available methods are complex and time consuming, but it may
      be possible to use tumour necrosis factor alpha (TNF alpha) concentration in
      stool as a marker of disease activity. We measured TNF alpha concentrations in
      stool samples from normal children, infants with diarrhoea, and children with
      inflammatory bowel disease in active and inactive phases of the disease. In 10
      normal children and 14 children with diarrhoea, median stool TNF alpha
      concentrations were 58 and 45 pg/g stool, respectively. Compared with diarrhoeal
      controls, stool TNF alpha concentrations were significantly increased in children
      with active Crohn's disease (n = 13, median 994 pg/g, p less than 0.0002) and
      active ulcerative colitis (n = 4, range 276-5982 pg/g, p less than 0.003). In
      patients with inactive disease, either as a result of surgery or treatment with
      steroids, the concentration of stool TNF alpha fell to those of controls.
      Measurement of stool TNF alpha concentrations may provide a simple way to monitor
      disease activity in inflammatory bowel disease.

PMID- 1345872
TI  - Ovarian ablation in early breast cancer: phoenix arisen?

PMID- 1345873
TI  - Long-term care in the UK: do we need it, does it matter, who will pay?

PMID- 1345874
TI  - Diabetes practice: the information gap.

PMID- 1345875
TI  - Schizophrenia: the rocky road from inpatient care.

PMID- 1345876
TI  - Ewing's sarcoma and its congeners: an interim appraisal.

PMID- 1345877
TI  - Allosteric effect of tetrahydrobiopterin cofactors on tyrosine hydroxylase
      activity.
AB  - Allostery of tyrosine hydroxylase was found by kinetical studies of partially
      purified tyrosine hydroxylase from clonal rat pheochromocytoma PC12h cells.
      Positive cooperativity toward the cofactors, (6R)-L-erythro-5,6,7,8
      tetrahydrobiopterin [(6R)BH4] and (6S)-L-erythro-5,6,7,8-tetrahydrobiopterin
      [(6S)BH4], was observed. It is indicated that biopterin might be the regulatory
      factor of the enzyme polymers, which changes the affinity for the cofactor
      itself. Moreover, the stereochemical structure of (6R)BH4, the naturally
      occurring cofactor, took an important role on the kinetical properties of the
      enzyme in concern with L-tyrosine.

PMID- 1345878
TI  - A new octopamine receptor class in locust nervous tissue, the octopamine 3 (OA3)
      receptor.
AB  - The insect neuronal 3H-octopamine binding site represents a new type of
      octopamine receptor. This receptor has pharmacological features that are
      characteristic for all known octopamine receptors, but it is possible to
      distinguish this receptor class from all others using either agonists or
      antagonists. The quantitative determination of the pharmacological relationships
      to the other octopamine receptor classes could demonstrate greatest homology with
      both class 2 (OA2A and OA2B) receptors. Therefore, the neuronal octopamine
      receptor should be named a class 3 receptor (OA3). A new and simple
      classification scheme for octopamine receptors which enables classification of
      the new receptor class is established using antagonists.

PMID- 1345879
TI  - Differential effects of opioid receptor agonists on nociception and cAMP level in
      the spinal cord of monoarthritic rats.
AB  - Changes in functional responsiveness of spinal opioid receptors in monoarthritic
      rats were investigated at the behavioral and the molecular level. After
      intrathecal administration of morphine, D-Ala2-D-Leu5-enkephalin (DADLE), D-Pen2
      D-Pen5-enkephalin (DPDPE) and dynorphin monoarthritic rats showed an enhanced
      antinociceptive response as measured by a tail-flick latency. No such changes
      were observed following administration of the selective kappa agonists U50,488H
      and U69,593. The opioid mu and delta receptor agonists (0.1-1.0 microM) inhibited
      the basal, as well as the forskolin-stimulated cAMP formation in spinal cord
      slices obtained from monoarthritic rats, whereas no significant changes were
      found in control animals. Higher concentrations of the mu and delta opioid
      receptor agonists were required to attenuate the cAMP level in spinal cord of
      control animals. The selective kappa agonists U50,488H and U69,593 did not
      influence the cAMP formation in monoarthritic or control animals. Additionally,
      we found that the GppNHp-stimulated level of cAMP was higher in the spinal cord
      slices of monoarthritic rats, which points to an enhanced responsiveness of the
      adenylate cyclase effector system to the action of this GTP analog. Our data
      suggest that the enhanced antinociceptive response to intrathecally administered
      opioids in monoarthritic rats may be connected with the increased sensitivity of
      adenylate cyclase to the inhibitory effects of mu and delta agonists.

PMID- 1345880
TI  - Acute exacerbations of COPD. How to evaluate severity and treat the underlying
      cause.
AB  - Acute exacerbations of chronic obstructive pulmonary disease occur often.
      Severity should be established by signs and symptoms and by reference to baseline
      pulmonary function test results when necessary. If the exacerbation is mild to
      moderate, treatment should include antibiotics, theophylline, beta agonists, and
      mucolytics. Severe exacerbations should be treated with these agents plus
      supplemental oxygen, intravenous corticosteroids, and, when appropriate,
      intubation and mechanical ventilation.

PMID- 1345881
TI  - Treatment of rheumatoid arthritis. New thoughts on the classic pyramid approach.
AB  - Treatment of rheumatoid arthritis can be quite challenging. Toxicity profiles of
      the various anti-inflammatory agents are often unacceptable, mainly because of
      gastrointestinal intolerance or bleeding. In addition, epidemiologic data suggest
      that rheumatoid arthritis is a disease with substantial morbidity and increased
      mortality. Consequently, newer trends in therapy involve earlier use of remittive
      agents as well as use of low-dose steroids. These modifications of the classic
      pyramid approach and the investigation of other methods may significantly
      influence the future of rheumatoid arthritis therapy and improve quality of life
      in those with the disease.

PMID- 1345882
TI  - Pharmacologic treatment of COPD. Optimum therapy for ambulatory patients.
AB  - Chronic obstructive pulmonary disease (COPD) has a wide variety of
      pathophysiologic mechanisms that involve the bronchi, bronchioles, and acini. For
      typical patients, first-line treatment with inhaled beta 2-selective agonists or
      ipratropium bromide (Atrovent) significantly improves lung function with minimal
      side effects. Theophylline is no longer routinely used as a first-line agent for
      the treatment of COPD but may be a useful addition to therapy if proper attention
      is given to serum drug levels and symptoms of toxicity. Oral prednisone is useful
      as an adjunctive agent for patients with serious disease who do not respond to
      other agents; a therapeutic trial showing objective evidence of benefit from this
      drug is essential. Mucolytics have recently been shown to have a role in
      improving lung function and also may be useful as adjunctive therapy.

PMID- 1345883
TI  - Cholesterol lowering by alpha-linolenic acid.

PMID- 1345884
TI  - Pharmacological treatment of obesity. Satellite symposium to the 6th
      International Congress of Obesity. Yokohama, Japan, October 18-20, 1990.

PMID- 1345885
TI  - Alpha-2 adrenoceptors in lipolysis: alpha 2 antagonists and lipid-mobilizing
      strategies.
AB  - The lipid-mobilizing and thermogenic effects of several alpha 2 antagonists were
      explored. Studies were undertaken in humans and in the dog, which possess fat
      cell alpha 2-adrenergic receptors (alpha 2-AR) and beta-adrenergic receptors
      (beta-AR) that are very similar. Yohimbine (alpha 2-AR antagonist) was used in
      humans whereas other recent alpha 2 antagonists were used in dogs. Oral yohimbine
      (0.2 mg/kg) promoted a lasting increment of plasma nonesterified fatty acids
      (NEFAs) and noradrenaline concentrations without significant action on
      cardiovascular parameters or insulin secretion. In dogs, a direct correlation
      between the variations of plasma NEFA and noradrenaline concentrations induced by
      alpha 2 antagonists (1.2 mmol/kg iv) was observed; a result supporting the
      relationship between lipolysis and the pharmacologic activation of the
      sympathetic nervous system. Cardiovascular effects were almost absent whereas a
      long-lasting thermogenic effect was observed. The lipid-mobilizing effect of
      alpha 2 antagonists is mainly attributable to the increase in synaptic
      noradrenaline. The potential interest of alpha 2 antagonists in diet therapy is
      discussed.

PMID- 1345886
TI  - The antidiabetic beta 3-adrenoceptor agonist BRL 26830A works by release of
      endogenous insulin.
AB  - A beta 3-adrenoceptor agonist, BRL 26830A, has been shown to have antiobesity and
      antidiabetic actions. However, the insulin-release mechanism of this agent is not
      well understood. Therefore, we tested the hypothesis that BRL 26830A promotes
      insulin release via beta 3 receptors on pancreatic-islet beta cells by using both
      in vivo and in vitro studies. In ICR mice fasted for 48 h, BRL 26830A
      significantly stimulated insulin release and markedly decreased the glucose
      level. Administration of a non-selective beta-receptor antagonist 30 min before
      BRL 26830A injection completely inhibited insulin release and the reduction of
      the glucose level. Neither beta 1- nor beta 2-selective antagonists produced the
      same effect. In the in vitro study with rat pancreatic-islet cell culture, BRL
      26830A and its free acid BRL 28410 did not promote insulin secretion. The results
      of the in vivo studies support our hypothesis, but the results of the in vitro
      study showed some discrepancies.

PMID- 1345887
TI  - Pharmacology of thermogenic drugs.
AB  - Thermogenic combinations of ephedrine with caffeine and newer selective beta 3
      agonists are being assessed for the treatment of obesity. The actions of beta
      agonists may be multifaceted, with acute stimulation of thermogenic mechanisms in
      various tissues. During chronic treatment recruitment of brown fat may occur and
      hypertrophy of skeletal muscle may occur and simultaneously increase lean body
      tissue and reduce fat mass by stimulation of lipolysis and energy expenditure.
      The weight-reducing effect of an ephedrine-caffeine combination was superior to
      placebo treatment during 24 wk of energy restriction in obese women, whereas
      caffeine and ephedrine separately had no effect. In a second study it was found
      that ephedrine-caffeine compared with placebo preserved fat-free mass and
      enhanced fat loss, which could be accounted for both by anorexia (75%) and by
      increased thermogenesis (25%). The ephedrine-caffeine compound seems useful for
      the treatment of obesity and may serve as reference in the clinical assessment of
      new beta-agonists.

PMID- 1345888
TI  - Thermogenic effects of various beta-adrenoceptor agonists in humans: their
      potential usefulness in the treatment of obesity.
AB  - The thermogenic effect of various beta-agonists was studied in humans by using
      indirect calorimetry. Epinephrine was found to be markedly thermogenic: at
      infusion rates of 0.01, 0.03, and 0.1 microgram.min-1.kg fat-free mass-1 resting
      energy expenditure (REE) increased by 8%, 16%, and 29%, respectively; in
      addition, a dose-dependent increase in heart rate was observed. Dopamine at high
      infusion rates also induces beta-agonist effects: at 5 and 10 micrograms.min-1.kg
      1, REE increased by 6% and 15%, respectively, an effect that could be mediated by
      the release of endogenous norepinephrine. The phenethanolamine derivative Ro 16
      8714 given per os at a single dose of 5 and 20 mg led to an increase of REE of
      10% and 21%, whereas heart rate was enhanced by 8% and 49%, respectively. The new
      beta-adrenoreceptor agonist Ro 40-2148, given per os to six normal-weight young
      subjects at a single dose of 200 or 400 mg, induced no significant change in REE,
      whereas after 800 mg, REE was increased in all subjects (+3 to +17%, mean + 8%)
      without inducing tachycardia.

PMID- 1345889
TI  - BRL 35135, a potent and selective atypical beta-adrenoceptor agonist.
AB  - BRL 35135, via its active deesterified metabolite BRL 37344, is a potent example
      of a new group of beta-adrenoceptor agonists that stimulate selectively a novel
      beta adrenoceptor that was originally shown to be present in brown adipose tissue
      in rodents. BRL 35135 produces a dose-related increase in energy expenditure in
      rodents and, in genetically obese (ob/ob) mice, a dose of 0.5 mg.kg-1.d-1 has
      significant antiobesity activity. This weight loss is entirely due to loss of
      fat; muscle protein is preserved. In studies in nonobese men, BRL 35135 (0.1
      mg/kg) increased both resting metabolic rate and the thermic response to a
      glucose load. BRL 35135 is effective in improving glucose tolerance in
      genetically obese (ob/ob) mice and obese Zucker (fa/fa) rats at doses that have
      no significant antiobesity activity. The improved glucose tolerance is the result
      of significant improvement in insulin sensitivity. In 10-d studies in obese and
      diabetic patients, BRL 35135 produced improvements in glucose tolerance and
      insulin sensitivity.

PMID- 1345890
TI  - Clinical studies with the beta-adrenoceptor agonist BRL 26830A.
AB  - BRL 26830A is a beta-adrenoceptor agonist drug that shows a high degree of
      selectivity for thermogenesis and has potential as an antiobesity agent. We
      undertook a double-blind trial in 40 obese subjects who received either BRL
      26830A or placebo for 18 wk. All were prescribed a 3.35 MJ (800 kcal) diet.
      Weight loss was 15.4 +/- 6.6 (SD) kg on BRL 26830A compared with 10.0 +/- 5.9 kg
      on placebo (P less than 0.02). The relative weight losses were 0.93% and
      0.61%/wk, respectively. Urinary nitrogen excretion was similar in both groups and
      skinfold measurements indicated a 4-kg difference in fat lost, suggesting that
      weight loss was mainly from adipose tissue. Psychological assessments showed that
      BRL 26830A had no adverse effect on mood and no effect on hunger or satiety.
      Tremor was experienced by 12 of 16 treated subjects who completed the study. It
      was generally rated as mild, occurred 1 h after dosing, and tended to diminish
      with time on treatment. Subsequent analysis of the tremor suggested that it is an
      exaggeration of physiological tremor mediated through skeletal muscle beta 2
      adrenoceptors.

PMID- 1345891
TI  - ICI D7114: a novel selective adrenoceptor agonist of brown fat and thermogenesis.
AB  - Increasing energy expenditure by treatment with thermogenic drugs is not new, but
      available drugs have suffered from the problem of lack of selectivity. In the
      last decade two key findings have allowed the development of selective
      thermogenic drugs that have promise in the treatment of obesity. 1) The
      recognition that brown adipose tissue (BAT) plays a role in compensatory
      increases in energy expenditure has allowed an approach directed at a target
      organ. 2) The demonstration showing that increases in the activity of BAT may be
      modulated by an atypical (beta 3) adrenoceptor has led to the development of a
      new peripherally acting beta-adrenoceptor agonist ICI D7114, which stimulates
      thermogenesis at doses that have little effect on beta 1 or beta 2 adrenoceptors.
      Treatment with the compound activates BAT and thermogenesis even in species and
      situations where the intrinsic capacity is low. 3) The compound has beneficial
      effects in animal models of obesity and disturbed glucose and lipid homeostasis.

PMID- 1345892
TI  - Enhanced staining for Leu M1 (CD15) in Hodgkin's disease using a secondary
      antibody specific for immunoglobulin M.
AB  - The utility of staining for Leu M1 (CD15) as a diagnostic aid in Hodgkin's
      disease has been questioned because of a relative lack of specificity and
      sensitivity. Furthermore, interpretation is often made difficult by staining that
      tends to be weak and focal. Because the murine monoclonal anti-Leu M1 antibody is
      of immunoglobulin M type, it is reasonable to wonder whether improved
      immunohistochemical staining might result from use of a secondary goat antibody
      specific for the mouse mu heavy chain instead of the traditional one against
      mouse immunoglobulin. The two methods were compared, using a biotin-avidin
      detection system, on paraffin sections from 15 cases of Hodgkin's disease: 9
      nodular sclerosing, 1 mixed cellularity, and 5 of nodular lymphocytic and
      histiocytic (L&H) type. In the nodular sclerosing/mixed cellularity group, the mu
      specific detection method resulted in a greater number of cases with reactive
      Hodgkin's cells (7 versus 5), stained an average of more than three times as many
      neoplastic cells in each case (49% versus 14%), and usually produced staining
      that was distinctly more intense, often in a membrane and paranuclear
      distribution characteristic of Leu M1 in Hodgkin's cells. In the noLeu M1 in
      Hodgkin's cells. In the nodular L&H group, 1 case showed weak, focal staining
      with the newer method. None of the L&H cases stained using the traditional
      technique. It is concluded that use of a second-stage antibody that is directed
      specifically against mu heavy chains results in an improvement in
      immunohistochemical staining for Leu M1 in paraffin sections, which is of
      practical significance.

PMID- 1345893
TI  - Case report: nifedipine-rifampicin interaction attenuates the effect on blood
      pressure in a patient with essential hypertension.
AB  - A 72-year-old woman with 5-year history of essential hypertension developed
      peritoneal tuberculosis. The patient's hypertension, which had been well
      controlled by long-acting nifedipine, deteriorated after the administration of
      rifampicin, an antitubercular agent. During use of nifedipine and rifampicin,
      both the peak plasma concentration and the area under the curve of nifedipine
      decreased markedly to about 40% of those without rifampicin. The findings suggest
      that rifampicin may increase the elimination of nifedipine, presumably by
      induction of its hepatic metabolism. Nisoldipine, another calcium antagonist,
      also failed to lower the patient's blood pressure, when given in combination with
      rifampicin. Taken together, these findings indicate that more caution should be
      urged when calcium antagonist is prescribed along with rifampicin.

PMID- 1345894
TI  - Current Issues in ENT Infectious Disease. Symposium, March 16-17, 1990, Orlando,
      Florida.

PMID- 1345895
TI  - Reversal of CD45R isoform switching in CD8+ T cells.
AB  - Both CD4+ and CD8+ T cells express either CD45RA or CD45R0 isoform of CD45R in an
      exclusive way. Recent reports have shown that CD45RA+ T cells lose CD45RA and
      gain CD45R0 upon activation. This switching has been suggested to be irreversible
      although more recently, examples of reversal of CD45R isotype switching in CD4+ T
      cells have been reported. We report here that freshly isolated unprimed CD8+ T
      cells, when activated with PHA, temporarily lose CD45RA but reexpress an
      intermediate level of CD45RA 2-3 weeks after activation with PHA. This reversal
      seems to take place much more slowly in unprimed CD4+ T cells: the majority of
      CD4+ T cells that had lost CD45RA and gained CD45R0 remained CD45RA-CD45R0+ in 3
      weeks after the stimulation. Also, long-term CD8+ CD45RA+ T cell lines stimulated
      with PHA or OKT3 showed even more rapid recovery of CD45RA while PPD-specific
      CD4+ T cell clones retained the original CD45R0 phenotype 3 weeks after
      stimulation with PPD or PHA.

PMID- 1345896
TI  - Changes in the populations of null, NK1.1+, and Thy1lo lymphocytes in the bone
      marrow of tumor-bearing mice: effect of indomethacin treatment.
AB  - Mouse bone marrow produces many "null" lymphocytes which lack B and T lineage
      markers (B220-Thy1-). A subset of these cells expresses the natural killer (NK)
      cell marker, NK1.1. In addition, some rapidly renewed bone marrow lymphocytes
      express low intensities of Thy1 (Thy1lo). In view of their possible implication
      in tumor-host interactions these various cell populations have now been examined
      in mice injected with either the nonmetastatic Ehrlich ascites (EA) tumor or the
      Lewis lung carcinoma (LLc), a highly metastatic solid tumor. In each case, the
      number of null lymphocytes, as defined by a lack of radioautographic labeling of
      either B220 glycoprotein or Thy1, increased markedly in both the bone marrow and
      spleen. Treatment with the prostaglandin inhibitor, indomethacin, enhanced the
      increase in null cells in the bone marrow and spleen of LLc-bearing mice. The
      number of null small lymphocytes expressing NK1.1, as detected by combined
      radioautographic and immunoperoxidase techniques, increased almost 30-fold in LLc
      bearing mice. The number of Thy1lo small lymphocytes increased in parallel with
      null cells during EA tumor growth. The findings accord with the hypothesis that
      the null lymphocyte population produced in mouse bone marrow includes newly
      formed NK lineage cells which sequentially express NK1.1 and Thy1lo. The present
      work demonstrates that the populations of null, NK1.1+, and Thy1lo lymphocytes in
      mouse bone marrow expand rapidly during the early growth of transplanted tumors,
      the initial increase in null lymphocytes apparently being curtailed by
      prostaglandin production. The results suggest that the production of null
      lymphocytes in mouse bone marrow is responsive to tumor development, possibly
      providing cells to be involved in tumor-host interactions.

PMID- 1345897
TI  - Defect of CD2- and CD3-mediated activation pathways in T cells of atopic
      patients: role of interleukin 2.
AB  - In the present work we analyzed the proliferative response of T lymphocytes from
      11 atopic patients stimulated in vitro via either the CD2 or the CD3 pathway of
      cell activation. In both cases we found a significant decrease of thymidine
      incorporation in cell DNA in comparison with T cells from normal donors. The
      mechanism of this impaired proliferative response was analyzed. Atopic patients'
      T cells were found to secrete low quantities of interleukin 2 (IL2) and to
      express low amounts of Tac antigen, measured as both a percentage of Tac-positive
      cells and a mean fluorescence intensity of Tac antigen per cell. Addition of
      recombinant IL2 to cultures completely restored both cell proliferative response
      and Tac antigen expression. This effect was specific of IL2 since addition of IL1
      or IL4 did not significantly affect T cell proliferative response. We conclude
      that atopic patients' T lymphocytes have a defect in both CD2 and CD3 pathways of
      cell activation relying on impairment of IL2 production, without involving IL2
      responsiveness or other lymphokine defects.

PMID- 1345898
TI  - Symposium: Future directions of cytokine and immunoglobulin therapy. Tucson,
      Arizona, January 11-12, 1991.

PMID- 1345899
TI  - Segregation of structural collagen genes in adolescent idiopathic scoliosis.
AB  - The etiology of idiopathic scoliosis remains unknown. The condition results in a
      characteristic deformity of the spine and surrounding tissues. Both Types I and
      II collagen are important constituents of the affected tissues, and thus
      defective collagens are reasonable candidates for the primary abnormality in
      adolescent idiopathic scoliosis (AIS). Direct analyses of the amount and
      solubility of collagen have revealed differences between normal individuals and
      those with AIS. However, these changes may be secondary to the mechanical effects
      of the spinal deformity. Segregation analysis was done of genetic markers linked
      to the structural genes encoding Types I and II collagen to test these candidate
      loci in four pedigrees with dominantly inherited AIS. In one pedigree, markers
      linked to both of the Type I collagen loci (COL1A1 and COL1A2) were found to be
      inherited independently of the abnormal phenotype. Two pedigrees were discordant
      at one of the Type I loci. The condition also segregated independently of the
      locus for Type II collagen (COL2A1) in three pedigrees. This is evidence against
      idiopathic scoliosis generally being caused by mutations in the Types I and II
      collagen genes.

PMID- 1345900
TI  - Effect of a beta 2-agonist (broxaterol) on respiratory muscle strength and
      endurance in patients with COPD with irreversible airway obstruction.
AB  - The effect of broxaterol, a new beta 2-agonist, on respiratory muscle endurance
      and strength was studied in a double-blind, placebo-controlled, randomized
      crossover clinical trial in 16 patients with chronic obstructive pulmonary
      disease (COPD) with irreversible airway obstruction (FEV1 = 57.1 percent of
      predicted). One patient withdrew from the study because of acute respiratory
      exacerbation. Inspiratory muscle strength was assessed by maximal inspiratory
      pressure (MIP) and endurance time was determined as the length of time a subject
      could breathe against inspiratory resistance (target mouth pressure = 70 percent
      of MIP, Ti/Ttot = 0.4). Broxaterol (B) or placebo (P) was given orally for seven
      days at the dose of 0.5 mg three times a day with a washout period of 72 h
      between study treatments. Measurements were performed before administration of B
      or P and 2 h (six patients) or 8 h (nine patients) after the end of each
      treatment. No significant changes in FEV1 or FRC were observed after B or P
      suggesting that diaphragmatic length was maintained constant with each treatment.
      The MIP did not significantly change, while endurance time increased after B in
      the patients tested at 2 h (from 234.8 +/- 48.1 s to 284.0 +/- 48.0 s, p less
      than 0.05) and at 8 h (from 187.2 +/- 31.1 s to 258.2 +/- 40.4 s, p less than
      0.005). No changes were observed after P. Minute ventilation, airway occlusion
      pressure (P0.1), integrated electromyographic activities of the diaphragm (Edi),
      and intercostal parasternals (Eic) (normalized to the value obtained during MIP)
      showed no change during the endurance run with different treatments. We conclude
      that in a group of COPD patients with irreversible airway obstruction, B
      significantly improves respiratory muscle endurance, and that this does not arise
      as a result of an effect on neuromuscular drive or pulmonary mechanics, but may
      be mediated by peripheral factors.

PMID- 1345901
TI  - Electrophysiologic study of the effects of aminophylline and metaproterenol on
      canine myocardium.
AB  - Aminophylline and beta-adrenergic agonists are widely used in the treatment of
      obstructive lung diseases. It has been suggested that combined aminophylline and
      beta-agonist therapy may promote the development of atrial and ventricular
      arrhythmias. The effects of these agents in combination on myocardial conduction
      and tissue refractoriness have not been documented. We evaluated the
      electrophysiologic effects of intravenous aminophylline and inhaled
      metaproterenol on canine myocardium. Aminophylline produced significant decreases
      from baseline in the AH interval (85 +/- 6.5 [SD] to 63 +/- 4.1 ms [p less than
      0.02]), Wenckebach cycle length (WCL) (226 +/- 8.7 to 182 +/- 5.8 ms [p less than
      0.02]), and ventricular effective refractory period (VERP) (166 +/- 6.0 to 148 +/
      4.9 ms [p less than 0.01]). Metaproterenol produced similar results, except
      metaproterenol significantly decreased the atrial effective refractory period
      (AERP) from 152 +/- 6.6 to 130 +/- 3.2 ms (p less than 0.02), an effect not seen
      with aminophylline alone. Metaproterenol also produced significantly greater
      reductions in AH interval and WCL, as well as a greater increase in heart rate
      than aminophylline did. When compared with aminophylline alone, combined
      metaproterenol and aminophylline therapy produced significantly greater
      reductions in the AH interval (63 +/- 4.1 versus 48 +/- 1.2 ms for combined
      therapy [p less than 0.01]), HV interval (32 +/- 1.2 versus 28 +/- 2.0 ms for
      combined therapy [p less than 0.02]), WCL (182 +/- 5.8 versus 150 +/- 7.1 ms for
      combined therapy [p less than 0.02]), and VERP (148 +/- 4.9 versus 132 +/- 2.0 ms
      for combined therapy [p less than 0.02]). We conclude that both aminophylline and
      metaproterenol significantly enhance AV nodal and His-Purkinje conduction.
      Metaproterenol produced significant changes in both atrial and ventricular tissue
      refractoriness. Metaproterenol produced significantly greater changes than
      aminophylline alone, and inhaled metaproterenol combined with intravenous
      aminophylline produced greater changes in AV nodal and His-Purkinje conduction
      and ventricular refractoriness than did aminophylline alone in a canine model.

PMID- 1345902
TI  - Role of physician assistants in critical care units.

PMID- 1345903
TI  - Release of endosomal content induced by plasma membrane tension: video image
      intensification time lapse analysis.
AB  - Rhodamine-labeled vinculin microinjected into chicken embryo fibroblasts and
      rhodamine-labeled alpha 2-macroglobulin added to the fibroblast culture medium
      were sequestered in endocytotic vesicles and digested. When a sealed
      microcapillary coated with fibronectin or polylysine was attached to the
      fibroblasts and pulled at speeds of 100-200 microns/h, stretching the plasma
      membrane, a variable fraction of the endosomes released the rhodamine label.
      Release from individual vesicles was rapid, reaching completion in less than 30
      to 120 s. The microfilament disrupting agent cytochalasin B prevented release, as
      did the microtubule stabilizing drug taxol. Colcemide, which disrupts
      microtubules, did not inhibit the release. Release was dependent on extracellular
      calcium, as it was prevented by 10 mM EGTA in the incubation medium. We postulate
      that opening of vesicular channels consequent to centripetal transmission of
      tension generated in the plasma membrane along microfilaments may be a mechanism
      of release of endosomal content.

PMID- 1345905
TI  - Different recognition of transgenic HLA-DQw6 molecules by mouse CD4+ and CD8+ T
      cells.

PMID- 1345906
TI  - The B6.CE-Lyb-2c:Mup-1a mouse strain contains the interferon-alpha genes from
      C57BL/6.

PMID- 1345904
TI  - Impairment of MHC class I transcription in a mutant bovine B cell line.
AB  - To better define the regulation and expression of bovine major histocompatibility
      complex (MHC) antigens, the bovine B lymphoblastoid cell line, BL3, was exposed
      to gamma-irradiation and surviving cells were immunoselected for MHC class I
      antigen loss. The resulting class I expression loss variant, BL3.1, was
      characterized at both the protein and genetic levels to ascertain the nature of
      the defect. Microfluorimetry analysis revealed a 3--5-fold surface density
      reduction of all class I products on BL3.1 cells relative to the parental BL3
      cells. This decreased surface expression was specific for MHC class I and not for
      MHC class II or the non-MHC-linked gene product, immunoglobulin (Ig). Northern
      and quantitative slot blot analyses demonstrated a corresponding diminution of
      class I RNA in BL3.1 suggesting a transcriptional level defect. Nuclear run-off
      and transcription inhibition experiments confirmed no post-transcriptional
      changes while Southern blot analysis provided no evidence for alterations within
      or near the class I genes. To help elucidate the mechanism of altered class I
      expression, the parent, BL3, and variant, BL3.1, were cultured with factors known
      to enhance MHC class I transcription. Interferon (IFN)-gamma, lipopolysaccharide
      (LPS), and activated peripheral blood lymphocyte (PBL) supernatant cultured with
      both cell lines induced MHC class I transcription and surface expression 2--3
      fold greater than the untreated controls. It is likely, therefore, that a genetic
      alteration outside of the class I genes has occurred within BL3.1 impairing
      expression of MHC class I.

PMID- 1345907
TI  - A T-cell receptor gamma delta-specific monoclonal antibody detects a V gamma 5
      region polymorphism.

PMID- 1345908
TI  - Mucosal immune response to RDEC-1 infection: study of lamina propria antibody
      producing cells and biliary antibody.
AB  - Infection of rabbits with Escherichia coli RDEC-1 is a useful model for diarrheal
      disease caused by mucosally attaching E. coli. Understanding of the protective
      immunity induced by RDEC-1 infection in rabbits should provide information useful
      in the design of vaccines for protection against this infection and other
      mucosally attaching organisms as well. Thus, to define the time course and
      location of specific immunoglobulin A secretion in relation to bacterial
      colonization during primary RDEC-1 infection, we infected rabbits with RDEC-1,
      which express AF/R1 adherence pili, and compared sites of anti-AF/R1 antibody
      containing cells in the intestinal mucosa with the sites of luminal colonization
      and mucosal attachment of RDEC-1. Also, anti-AF/R1 antibodies in intestinal
      fluids and bile were measured by enzyme-linked immunosorbent assay, and
      attachment sites of RDEC-1 to the intestinal epithelium were determined by
      immunohistochemical examination. Anti-AF/R1 pilus antibody-containing cells were
      most numerous in the proximal intestine (duodenum and jejunum). In contrast, both
      luminal colonization and attachment of RDEC-1 to epithelial cells were densest in
      the distal intestine (cecum and colon). Anti-AF/R1 antibodies were present in
      approximately equal amounts in fluids collected from all levels of the gut after
      week 1 postinfection. Anti-AF/R1 antibody levels in undiluted bile exceeded those
      in gut flushes by at least 2 orders of magnitude. Loss of RDEC-1 attachment to
      epithelial cells preceded resolution of diarrheal illness despite the presence of
      large numbers of organisms in the intestinal lumen. Our studies indicate that
      during RDEC-1 infection (i) sites of greatest mucosal anti-AF/R1 antibody
      secretion are proximal to sites of maximal RDEC-1 luminal colonization and
      attachment, (ii) bile is a major source of specific antibodies in the intestinal
      lumen, and (iii) interference with RDEC-1 attachment to epithelial cells may
      permit resolution of disease.

PMID- 1345910
TI  - Role of nitrogen regulator I (NtrC), the transcriptional activator of glnA in
      enteric bacteria, in reducing expression of glnA during nitrogen-limited growth.
AB  - During nitrogen-limited growth, transcription of glnA, which codes for glutamine
      synthetase, requires sigma 54-RNA polymerase and the phosphorylated from the
      nitrogen regulator I (NRI; also called NtrC). In cells in which the lac promoter
      controlled expression of the gene coding for NRI, increasing the intracellular
      concentration of NRI lowered the level of glutamine synthetase. The reduction in
      glutamine synthetase does not appear to result from the NRI-dependent
      sequestering of any protein that affects transcription of glnA. Our results also
      suggest that the negative effect of a high concentration of NRI on glnA
      expression is a major determinant of the level of glutamine synthetase activity
      in nitrogen-limited cells of a wild-type strain. We propose that the inhibition
      results from an impairment of the interaction between NRI-phosphate and RNA
      polymerase that stimulates glnA transcription. We discuss a model that can
      account for this reduction in glutamine synthetase.

PMID- 1345909
TI  - R-plasmid-encoded adhesive factor in Klebsiella pneumoniae strains responsible
      for human nosocomial infections.
AB  - Klebsiella pneumoniae strains involved in hospital outbreaks of nosocomial
      infections, such as suppurative lesions, bacteremia, and septicemia, were
      resistant to multiple antibiotics including broad-spectrum cephalosporins.
      Epidemiologic investigations revealed that the reservoir for these K. pneumoniae
      strains was the gastrointestinal tracts of the patients. The study of the
      adherence ability of the strains reported here showed that these bacteria adhered
      to the microvilli of the Caco-2 cell line. This adhesion was mediated by a
      nonfimbrial protein with a molecular mass of 29,000 Da designated CF29K.
      Pretreatment of bacteria with antibodies raised against CF29K or Caco-2 cells
      with purified CF29K prevented the adhesion of K. pneumoniae strains to Caco-2
      cells. CF29K immunologically cross-reacted with the CS31A surface protein of
      Escherichia coli strains involved in septicemia in calves. Genes encoding CF29K
      were located on a high-molecular-weight conjugative R plasmid, which transferred
      to E. coli K-12. Transconjugants expressed a large amount of CF29K protein and
      adhered to the brush border of Caco-2 cells. These findings show that K.
      pneumoniae strains were able to colonize the human intestinal tract through a
      plasmid-encoded 29,000-Da surface protein. Hybridization experiments indicated
      that the gene encoding resistance to broad-spectrum cephalosporins by the
      production of CAZ-1 enzyme and the gene encoding the adhesive property to
      intestinal cells were both located on a 20- to 22-kb EcoRI restriction DNA
      fragment. Genes encoding aerobactin and the ferric aerobactin receptor were also
      found on this R plasmid.

PMID- 1345911
TI  - Analysis of the autolysins of Bacillus subtilis 168 during vegetative growth and
      differentiation by using renaturing polyacrylamide gel electrophoresis.
AB  - The autolysins of Bacillus subtilis 168 were analyzed by sodium dodecyl sulfate
      (SDS)-polyacrylamide gel electrophoresis with substrate-containing gels. Four
      bands of vegetative autolytic activity of 90, 50, 34, and 30 kDa (bands A1 to A4)
      were detected in SDS and LiCl extracts and in native cell walls by using B.
      subtilis 168 vegetative cell walls as the substrate incorporated in the gel. The
      four enzyme activities showed different substrate specificities and sensitivities
      to various chemical treatments. The autolysin profile was not medium dependent
      and remained constant during vegetative growth. During sporulation, band A4
      greatly increased in activity just prior to mother-cell lysis. No germination
      associated changes in the profile were observed, although a soluble 41-kDa
      endospore-associated cortex-lytic enzyme was found. By using insertionally
      inactivated mutants, bands A1 and A2 were positively identified as the previously
      characterized 90-kDa glucosaminidase and 50-kDa amidase, respectively. The common
      filamentous phenotype of various regulatory mutants could not be correlated to
      specific changes in the autolysin profile.

PMID- 1345912
TI  - Translational control of pyrC expression mediated by nucleotide-sensitive
      selection of transcriptional start sites in Escherichia coli.
AB  - Expression of the pyrC gene, which encodes the pyrimidine biosynthetic enzyme
      dihydroorotase, is negatively regulated by pyrimidine availability in Escherichia
      coli. To define the mechanism of this regulation, an essential regulatory region
      between the pyrC promoter and the initial codons of the pyrC structural gene was
      identified. Mutational analysis of this regulatory region showed that the
      formation of a hairpin at the 5' end of the pyrC transcript, which overlaps the
      pyrC ribosome binding site, is required for repression of pyrC expression.
      Formation of the hairpin appears to be controlled by nucleotide-sensitive
      selection of the site of pyrC transcriptional initiation. When the CTP level is
      high, the major pyrC transcript is initiated with this nucleotide at a position
      seven bases downstream of the pyrC -10 region. This transcript is capable of
      forming a stable hairpin at its 5' end. When the CTP level is low and the GTP
      level is high, conditions found in cells limited for pyrimidines, the major pyrC
      transcript is initiated with GTP at a position two bases further downstream. This
      shorter transcript appears to be unable to form a stable hairpin at its 5' end.
      These results suggest a model for regulation in which the longer pyrC transcripts
      are synthesized predominantly under conditions of pyrimidine excess and form the
      regulatory hairpin, which blocks pyrC translational initiation. In contrast, the
      shorter pyrC transcripts are synthesized primarily under conditions of pyrimidine
      limitation, and they are readily translated, resulting in a high level of
      dihydroorotase synthesis. The data also indicate that a low level of pyrimidine
      mediated regulation may occur at the level of transcriptional initiation.

PMID- 1345913
TI  - Mutations at Glu-32 and His-39 in the epsilon subunit of the Escherichia coli
      F1F0 ATP synthase affect its inhibitory properties.
AB  - A collection of amino acid substitutions at residues Glu-32 and His-39 in the
      epsilon subunit of the Escherichia coli F1F0 ATP synthase has been constructed by
      cassette mutagenesis. Substitutions for residue Glu-32 appeared to cause abnormal
      inhibition of membrane-bound F1 ATPase activity, and replacement of His-39 by
      Arg, Val, and Pro affected F1F0 interactions.

PMID- 1345914
TI  - Regulation of Anabaena sp. strain PCC 7120 glutamine synthetase activity in a
      Synechocystis sp. strain PCC 6803 derivative strain bearing the Anabaena glnA
      gene and a mutated host glnA gene.
AB  - The glnA gene from Synechocystis sp. strain PCC 6803 was cloned by hybridization
      with the glnA gene from Anabaena sp. strain PCC 7120, and a deletion-insertion
      mutation of the Synechocystis gene was generated in vitro. A strain derived from
      Synechocystis sp. strain PCC 6803 which contained integrated into the chromosome,
      in addition to its own glnA gene, the Anabaena glnA gene was constructed. From
      that strain, a Synechocystis sp. glnA mutant could be obtained by transformation
      with the inactivated Synechocystis glnA gene; this mutant grew by using Anabaena
      glutamine synthetase and was not a glutamine auxotroph. A Synechocystis sp. glnA
      mutant could not be obtained, however, from the wild-type Synechocystis sp. The
      Anabaena glutamine synthetase enzyme was subject to ammonium-promoted
      inactivation when expressed in the Synechocystis strain but not in the Anabaena
      strain itself.

PMID- 1345915
TI  - Interactions of leukocyte integrins with intercellular adhesion molecule 1 in the
      production of inflammatory vascular injury in vivo. The Shwartzman reaction
      revisited.
AB  - We have investigated the role of leukocyte-endothelial cell interactions in a
      rabbit model of hemorrhagic vasculitis. Microvascular injury was produced in the
      skin by intradermal injection of Salmonella typhosa endotoxin followed 20 h later
      by intravenous zymosan, which activates complement. Hemorrhagic necrosis develops
      in the "prepared" skin sites which is characterized by microthrombi, neutrophil
      aggregation, platelet and fibrin deposition, and massive extravasation of
      erythrocytes. Hemorrhage in these Shwartzman-like lesions was quantitated by
      99mTc-labeled autologous erythrocytes. Inhibition of the hemorrhagic response was
      obtained with mAb reactive with ICAM-1 as well as mAb against the leukocyte CD18
      when either was administered intravenously just before intravenous zymosan
      challenge. This observation suggests that an intravascular event occurring in
      response to complement activation is required for the development of hemorrhagic
      vasculitis. We hypothesize that agents which successfully prepare the skin for
      the Shwartzman response after their intradermal injection do so by promoting
      increased intercellular adhesion molecule 1 (ICAM-1) expression on the vascular
      endothelium. Activation of complement then induces CD11/CD18 expression on
      circulating leukocytes thus producing an intravascular CD11/CD18-ICAM-1
      (leukocyte-endothelium) adhesion event. Inhibition of intravascular leukocyte
      leukocyte aggregation with mAb against CD11b (Mac-1) showed partial inhibition of
      hemorrhage, while mAb against CD11a (LFA-1) showed no inhibitory activity. This
      type of cytokine-primed, neutrophil-dependent vascular damage may be a model of
      human vasculitic processes where microvascular damage is produced in the absence
      of immune-complex deposition.

PMID- 1345916
TI  - Genetic and pharmacological evidence for more than one human steroid 5 alpha
      reductase.
AB  - The enzyme steroid 5 alpha-reductase catalyzes the conversion of testosterone
      into the more potent androgen, dihydrotestosterone, and impairment of this
      reaction causes a form of male pseudohermaphroditism in which genetic males
      differentiate predominantly as phenotypic females. We previously isolated cDNA
      clones that encode a human steroid 5 alpha-reductase enzyme. Here, we report
      molecular and genetic studies demonstrating that the gene encoding this cDNA is
      normal in subjects with the genetic disease steroid 5 alpha-reductase deficiency.
      We further show that in contrast to the major steroid 5 alpha-reductase in the
      prostate and cultured skin fibroblasts, the cDNA-encoded enzyme exhibits a
      neutral to basic pH optima and is much less sensitive to inhibition by the 4-aza
      steroid, finasteride (MK-906). The results provide genetic, biochemical, and
      pharmacological support for the existence of at least two steroid 5 alpha
      reductase isozymes in man.

PMID- 1345918
TI  - Long-term CD4+ memory T cells from the spleen lack MEL-14, the lymph node homing
      receptor.
AB  - We have characterized the surface phenotype and function of long-lived, Ag
      specific memory CD4+ T cells generated in vivo by immunization with keyhole
      limpet hemocyanin (KLH). CD4+ T cells from the spleens of mice primed more than 2
      mo previously with KLH, produced high levels of IL-2 and IL-3, and low levels of
      IL-4 and IFN-gamma in response to in vitro restimulation with specific Ag. The
      KLH-primed T cells mediated carrier-specific helper activity for the antibody
      production by NIP-primed B cells in secondary in vitro responses to NIP-KLH.
      Subsets of CD4+ T cells from KLH-primed mice were isolated on the basis of
      surface CD45RB (23G2) by magnetic separation and were examined for functional
      capacity in several assays of Ag-specific recall. Virtually all of the secretion
      of IL-2, IL-3, IL-4, and IFN-gamma in response to restimulation with Ag in vitro
      was associated with, and considerably enriched in, the CD45RB- subset of CD4+ T
      cells. Similarly, carrier-specific helper function and Ag-specific proliferation
      in vitro were also confined to the CD45RB-, CD4+ subset of T cells, confirming
      the previous association of this surface phenotype with memory Th cell activity.
      We also examined expression of the lymphocyte homing receptor, MEL-14 (gp90MEL),
      which is required for lymphocyte extravasation to peripheral lymph nodes and is
      present in high levels on naive T cells. MEL-14 positive and negative subsets of
      CD4+ T cells from long term KLH-primed mice were evaluated for Ag-specific memory
      function in terms of lymphokine production, Ag-induced proliferation, and helper
      activity. Each of these functions was associated exclusively with the MEL-14-
      subset of CD4+ T cells, which exhibited responses comparable to the CD45RB-
      subset. These data indicate that memory Th cell function in the spleen is
      contained within the MEL-14-, CD45RB- subset of CD4+ T cells and suggest that
      memory helper cells may have different patterns of recirculation from naive T
      cells.

PMID- 1345917
TI  - Dual antigenic recognition by cloned human gamma delta T cells.
AB  - The function of gamma delta T cells is still elusive. The nature of the antigens
      that they recognize and the mode of presentation of these antigens are largely
      unknown. The majority of human peripheral gamma delta T cells bear a V gamma 9/V
      delta 2 T cell receptor, and display nonclonal reactivity to mycobacteria,
      without restriction by MHC. It is unknown whether these cells have clonal
      antigenic specificity as well. Here we describe rheumatoid arthritis-derived V
      gamma 9/V delta 2 T cell clones, displaying dual antigenic recognition: a
      nonclonal, MHC-unrestricted recognition of mycobacteria, and a clonal recognition
      of a short tetanus toxin peptide presented by HLA-DRw53, a nonpolymorphic class
      II MHC molecule associated with susceptibility to rheumatoid arthritis. This is
      the first evidence that V gamma 9/V delta 2 T cells can recognize nominal
      antigenic peptides presented by class II MHC molecules. These results suggest
      that much like alpha beta T cells, V gamma 9/V delta 2 cells may contribute to
      the immune response against foreign antigens in an antigen-specific and MHC
      restricted manner. The reactivity of these gamma delta T cells to mycobacteria
      may represent a superantigen-like phenomenon.

PMID- 1345920
TI  - CD31, a novel cell surface marker for CD4 cells of suppressor lineage, unaltered
      by state of activation.
AB  - In this study, we examined the role of CD31 as a cell surface marker for subsets
      of human CD4 cells. CD31, as defined by a newly developed mAb termed anti-1F11,
      can divide activated as well as resting CD4 cells into distinct functional
      subpopulations, based on its surface expression. Among CD4 cells freshly isolated
      from peripheral blood, anti-1F11 preferentially reacts with the CD45RA+ subset.
      The majority of helper activity for B cell IgG synthesis and memory function to
      recall Ag such as tetanus toxoid or mumps was found within the CD31- CD4 cell
      population, whereas CD31+ CD4 cells provided poor helper function for B cell IgG
      synthesis and were more responsive to Con A and autologous MHC (autologous MLR).
      The expression of CD31 on CD45RA+ CD4 cells did not change after activation,
      despite the loss of CD45RA from the cell surface. Conversely, CD31 was not
      acquired after activation of CD45RO+ CD45RA- CD4 cells. Furthermore, activated
      CD4 cells expressing CD31 can induce suppressor function for B cell IgG
      synthesis, whereas the reciprocal population of activated CD4 cells (CD31-)
      provide strong helper function for B cell IgG production. Finally, IL-4
      production could only be induced by stimulation with PMA and ionomycin in either
      resting or activated CD31- CD4 cells. Thus, CD31 may prove useful in defining CD4
      populations with reciprocal functional programs. Moreover, unlike other markers
      used for this purpose, the expression of CD31 does not change after activation
      and may serve as a more useful marker for identification of cells of suppressor
      or helper lineage.

PMID- 1345919
TI  - Characterization of a novel rat thymocyte costimulating antigen by the monoclonal
      antibody 1.3.
AB  - To define membrane-associated molecules that impart signals for the activation
      and expansion of double negative (DN) cells, mAb were raised against in vitro
      cultured rat DN cells. One such mAb, 1.3, stimulated proliferation of DN cells
      along with submitogenic concentrations of PMA and IL-2 without affecting the
      mobilization of Ca2+. The 1.3 mAb precipitated a heterodimeric protein from DN
      cells and kidney (130/110 kDa). Although the tissue distribution and biochemical
      characteristics of the 1.3 determinant resemble the neutral aminopeptidase (AP-N)
      first described as the thymocyte activating molecule in the mouse, other data are
      contradictory; AP-N message was not detected in mRNA from 1.3 positive cells and
      the AP-N gene was absent in the genomic DNA from rat DN hybridomas expressing
      high levels of 1.3 Ag. In addition, the 1.3 mAb did not affect AP-N enzyme
      activity suggesting that 1.3 mAb does not function through this enzyme to
      transduce signals for proliferation. Thus, the 1.3 mAb defines a new and
      important thymocyte costimulating Ag.

PMID- 1345921
TI  - Sustained engraftment of mice transplanted with IL-1-primed blood-derived stem
      cells.
AB  - IL-1 is considered the primary mediator of the acute phase response. One of the
      characteristic manifestations of this response is early neutrophilia that is
      probably caused by release of mature neutrophils from the bone marrow into the
      peripheral blood. In the present study, we assessed whether IL-1 had a similar
      releasing effect on the number of circulating progenitor cells and stem cells.
      Female BALB/c mice were injected i.p. with increasing (0.1-1.0 micrograms/mouse)
      concentrations of rhu-IL-1 alpha. IL-1 injection resulted in a marked dose
      dependent increase in the number of polymorphonuclear neutrophils, granulocyte
      macrophage colony-forming units (CFU-GM), and cells forming spleen colonies (CFU
      S day 8 and day 12). The maximal increase was found at 4 to 8 h after injection
      of 1 micrograms IL-1 per mouse, yielding a mean fivefold elevation in neutrophil
      count, and a mean 30-fold and 10-fold increase in the number of circulating CFU
      GM and CFU-S, respectively. In a subsequent series of experiments, lethally
      irradiated (8.5 Gy) female recipient animals were transplanted with 5 x 10(5)
      blood mononuclear cells derived from male IL-1-treated animals. Long-term
      survival was obtained in 68% of mice transplanted with peripheral blood cells
      derived from donor animals at 6 h after a single injection of 1 micrograms IL-1.
      The mean number of circulating CFU-GM in these donor animals was 557/ml blood. At
      6 mo after transplantation, greater than 95% of the bone marrow cells were of
      male origin, as determined using in situ hybridization with a Y-chromosome
      specific probe. In contrast, long-term survival was reached in less than 10% of
      mice transplanted with an equal number of blood cells derived from saline-treated
      controls or donor animals treated with a dose of 0.1 micrograms IL-1. These
      results indicate that a single injection of IL-1 induces a shift of hematopoietic
      progenitor cells and marrow repopulating cells into peripheral blood and that
      these cells can be used to rescue and permanently repopulate the bone marrow of
      lethally irradiated recipients.

PMID- 1345922
TI  - Tumor-bearing mice exhibit a progressive increase in tumor antigen-presenting
      cell function and a reciprocal decrease in tumor antigen-responsive CD4+ T cell
      activity.
AB  - Splenic CD4+ T cells from BALB/c mice bearing a syngeneic tumor (CSA1M) 2 to 3 wk
      after the inoculation with CSA1M cells produced IL-2 and macrophage-activating
      factor upon in vitro cultures. This lymphokine production was achieved without
      stimulation of these T cells with exogenous stimulating tumor Ag. However,
      elimination of APC from spleen cells resulted in almost complete abrogation of
      the capacity of CD4+ T cells to produce IL-2/macrophage-activating factor. The
      lymphokine production was regained when APC from CSA1M-bearing mice were added
      back to cultures. APC from normal or another syngeneic tumor (Meth A)-bearing
      mice failed to regain the lymphokine production. These observations demonstrated
      that the lymphokines were produced by CD4+ T cells from CSA1M-bearing hosts
      through their collaboration with APC binding CSA1M tumor Ag in the tumor-bearing
      state. The lymphokine-producing capacity of whole spleen cells from tumor-bearing
      mice reached the maximal level around 2 to 3 wk after tumor implantation but
      gradually decreased with the progress of tumor-bearing stages. Importantly, tumor
      bearing stage-related changes were observed in a different fashion in the
      capacities of anti-CSA1M CD4+ T cells vs CSA1M tumor Ag-binding APC. The capacity
      of APC increased with the progress of tumor-bearing stages as demonstrated by the
      stimulation of CSA1M-immunized T cells with APC from different CSA1M-bearing
      stages. In contrast, the reactivity of anti-CSA1M T cells to APC from a given
      CSA1M-bearing stage decreased with the tumor-bearing stage. These results
      demonstrate a stage-related increase tumor Ag-binding APC function, as well as a
      reciprocal reduction in tumor Ag-responsive CD4+ T cell activity.

PMID- 1345923
TI  - Long-term consequences of 239PuO2 exposure in dogs: persistent T lymphocyte
      dysfunction.
AB  - Young Beagle dogs were exposed by inhalation to aerosols of 239PuO2 and observed
      for their lifespans as part of a large, ongoing study of the biological effects
      of inhaled radionuclides. The purpose of our study was to compare certain immune
      responses of the 239PuO2-exposed dogs at middle age (7-10 years old) and old age
      (12-14 years old), with those of unexposed, age-matched or young (3-4 years old)
      animals. Some of the aged, exposed dogs had developed lung tumours. Lymphocyte
      proliferative responses to phytohaemagglutinin (PHA) were lower in aged control
      dogs than in either young or middle-aged control dogs. Both aged and middle-aged,
      radiation-exposed dogs had decreased responses to PHA when compared to age
      matched controls. Responses to concanavalin A (Con A) were not affected by age in
      control dogs, but tended to decrease in the oldest group of radiation-exposed
      dogs. Responses to both PHA and Con A were severely depressed in tumour-bearing
      dogs. The cytolytic activity of natural killer cells was not affected by age,
      radiation exposure, or tumour presence. We concluded that inhalation of 239PuO2
      by young Beagle dogs resulted in an earlier-than-normal decrease in the ability
      of T cells to respond to mitogenic stimulation. In other words the depressed
      responses to PHA that were observed might represent radiation-induced,
      accelerated ageing of the T cell response.

PMID- 1345924
TI  - Symposium report. Engineering, electromagnetic radiation and cancer treatment-
      organized on the occasion of the retirement of Professor Huibert Sowden Reinhold,
      Delft, The Netherlands, 19 April 1991.

PMID- 1345925
TI  - Ambiguity of the Brenner-Hall model.

PMID- 1345926
TI  - Ionization of polynucleotides and DNA in aqueous solution by 193 nm pulsed laser
      light: identification of base-derived radicals.

PMID- 1345927
TI  - Iron(II) sulphate (Fricke solution) oxidation yields for 8.9 and 13.6 keV X-rays
      from synchrotron radiation.
AB  - The oxidation yields (G) for 8.86 and 13.55 keV X-rays produced by synchrotron
      radiation were measured using an iron(II) sulphate (Fricke) solution.
      Monoenergetic X-rays were produced using a silicon crystal monochromator. The X
      rays were absorbed in 0.4 M sulphuric acid-iron(II) sulphate solution and FeIII
      ion yields were measured and corrected for escape fractions resulting from
      scattering using Monte Carlo calculations. Doses in the solution were determined
      using a thin window, parallel plate chamber calibrated against a primary standard
      free-air chamber at the Electrotechnical Laboratory (Osaka, Japan). Yields (G) of
      1.50 +/- 0.06 and 1.43 +/- 0.06 mumol J-1 were obtained for 8.86 and 13.55 keV X
      rays respectively.

PMID- 1345928
TI  - Oxygen effect for DNA double-strand break induction determined by pulsed-field
      gel electrophoresis.
AB  - The induction of DNA double-strand breaks (dsb) following irradiation under
      oxygenated and hypoxic conditions with and without misonidazole was measured by
      pulsed-field gel electrophoresis (PFGE) in a human bladder carcinoma cell line.
      The dose-response curve for DNA dsb detection by PFGE was biphasic with an
      apparent reduction in rate of dsb induced with dose. Oxygen enhancement ratios
      (OER) for cell survival (at a surviving fraction of 0.1) and for DNA damage
      assessed by PFGE (at 80% retained) were 2.0 and 3.0 respectively. Dose-modifying
      factors for misonidazole (15 mM), of 1.9 (survival) and 2.4 (DNA damage) were
      found. Although the magnitude of the inter-experiment variations limit the
      precision with which cell survival and DNA electrophoresis can be compared, the
      data do support a simple correlation between these two measures of response. When
      DNA dsb induction frequency was assessed from the number average molecular
      weight, values of 2.7 (+/- 0.3), 0.7 (+/- 0.1) and 2.6 (+/- 0.5) x 10(-9)
      dsb/bp/Gy were found for irradiation under oxic, hypoxic alone and hypoxic +
      misonidazole conditions respectively. This gives an OER of 3.9 and a DMF of 3.7.

PMID- 1345929
TI  - Radon: current challenges in cellular radiobiology.
AB  - Radon is by far the most important contributor to the collective dose equivalent.
      Most of what is known about the hazards of radon daughters comes from
      epidemiological studies of miners. There are a few well defined areas in which in
      vitro research can complement such studies: First, more data on the relative
      effects of differing energy (LET) alpha-particles would help: (1) understand the
      significance of the depth of sensitive cells in the bronchial epithelium--which
      varies between individuals, as well as between smokers and non-smokers, and
      between miners and non-miners; (2) understand the relative hazards of radon and
      thoron daughters. Second, reliable methods for predicting high LET responses from
      low LET response, would enable Japanese A-bomb survivor data to be applied with
      confidence. Third, understanding the effects of single-particle traversals of
      cells relative to multiple traversals could allow reliable extrapolation of
      epidemiological miner data to low exposures. Fourth, a better understanding of
      the nature of the interaction between tobacco and radiation damage would help
      predict the effect of radon on non-smokers.

PMID- 1345930
TI  - Repair of DNA strand breaks at hyperthermic temperatures in Chinese hamster ovary
      cells.
AB  - The repair of DNA double-strand breaks was measured by pH 7.2 filter elution in
      cells incubated at 25-45 degrees C either before or after X-irradiation. Exposure
      to 45 degrees C for 15 minutes immediately prior to X-irradiation significantly
      increased both the half-time for DNA double-strand break closure and the number
      of DNA double-strand breaks remaining in nuclear DNA 180 minutes after
      irradiation. Exposure to temperatures between 41 and 45 degrees C immediately
      after X-irradiation accelerated DNA double-strand break closure and resulted in
      no increase in the number of DNA double-strand breaks remaining in the cell's
      genome 180 minutes after irradiation. The results indicate either that the
      radiosensitization produced by the administration of hyperthermic temperatures
      before and after irradiation result from two characteristically different
      molecular mechanisms, or that neither the rate of DNA strand break closure nor
      the number of DNA strand breaks remaining in nuclear DNA after irradiation
      accurately predict hyperthermic radiosensitization. These conclusions assume that
      no DNA strand breaks are below the resolution of this DNA damage assay and that a
      comparison between cytotoxicity and DNA repair after exposure to high radiation
      doses is valid.

PMID- 1345931
TI  - Cellular recovery in two sub-lines of the L5178Y murine leukaemic lymphoblast
      cell line differing in their sensitivity to ionizing radiation.
AB  - Cellular recovery was assessed in two sublines of L5178Y murine lymphoma cells of
      differing radiosensitivity (LY-S and LY-A4) using low dose-rate irradiation and
      split-dose experiments. No increase in cell survival was observed in the LY-S
      cell line until the dose-rate was reduced to 2 cGy/min, whereas in the LY-A4 cell
      line 20 cGy/min was low enough to detect changes in survival. The extent of this
      change, as assessed by dose reduction factors at 2 logs of cell kill, was greater
      in the LY-A4 cell line. Fitting these data with the incomplete repair model of
      Thames led to anomalous values for the half-time of repair. In split-dose
      experiments the maximum observed recovery ratio increased as a function of dose
      in a manner that is consistent with the linear-quadratic equation. As was found
      previously with radiosensitive human tumour cells, the LY-S cell line showed more
      split-dose recovery at any given dose than the LY-A4 cell line.

PMID- 1345932
TI  - The transition from late G1 to early S phase is most vulnerable to the
      coclastogenic effect of ultraviolet radiation plus arsenite.
AB  - It has previously been reported that chromosome aberrations induced by
      ultraviolet (UV) radiation can be enhanced by treatment with sodium arsenite for
      24 h post-irradiation. Using synchronized CHO-K1 cells, it has now been
      established that cells in the transitional stage from late G1 to early S phase
      are most vulnerable to the coclastogenic effect of treatment with UV radiation
      and arsenite. This result cannot be explained by the special vulnerability of
      cells in the late G1 to early S transition to UV clastogenicity, as the
      coclastogenic effects of UV and caffeine or UV and arabinofuranosylcytosine were
      detected when treating the mid-S but not late-G1 or G2 phase cells.

PMID- 1345933
TI  - Radiomimetic cell cycle delay induced by tetranodecanoyl phorbol acetate is
      enhanced by caffeine and by the protein kinase inhibitor 2-aminopurine.
AB  - The tumour promoter and protein kinase C agonist, 12-O-tetranodecanoyl-phorbol-13
      acetate (TPA), has been reported to show a radiomimetic action because it
      transiently delays the passage of HeLa cells through the G2 phase, as do ionizing
      radiation and other DNA damaging agents. Caffeine is known to override the G2
      delay imposed by DNA damage; it is shown here that caffeine does not override the
      radiomimetic delay imposed by TPA in HeLa, but instead enhances it, without
      affecting G2 progression in control cells. Most of the other agents which more
      specifically affect some of the diverse range of caffeine targets either do not
      affect G2 progression after TPA, or delay G2 progression in control cells and
      exert a further delay in the presence of TPA. The exception is 2-aminopurine, a
      protein kinase inhibitor which has been shown to have an action similar to that
      of caffeine is allowing progression of the cell cycle to mitosis after the
      inhibition of DNA synthesis, without affecting normal cycle progression through
      G2. This agent, like caffeine, also has the contrary action of retarding cycle
      progression after TPA. It is concluded that the G2 delays induced by ionizing
      radiation and by TPA operate by different mechanisms, which are modulated in
      opposite senses by mechanisms involving protein kinase inhibition.

PMID- 1345934
TI  - In vitro and in vivo studies using BW12C: toxicity, haemoglobin modification and
      effects on the radiosensitivity of normal marrow and RIF-1 tumours in mice.
AB  - BW12C binds to haemoglobin, shifting the oxygen saturation curve to the left, and
      is under investigation as an inducer of tumour hypoxia. The intrinsic cellular
      toxicity of the drug to RIF-1 and EMT6 cells in monolayer culture was studied,
      and IC50 values of 100 micrograms ml-1 for 24 h exposure and 10 micrograms ml-1
      for 4-day exposure were measured. The LD50 (95% CL) in C3H mice was shown to be
      124 (118-130) mg kg-1 for normal, rapid i.v. injection of the drug, and 173 (164
      181) mg kg-1 for slow injection. The well-tolerated dose of 70 mg kg-1, used for
      all subsequent studies, was shown to produce a maximum haemoglobin modification
      of 70% 5 min after i.v. administration. This effect decayed with a half-life (+/-
      2 se) of 76 +/- 8 min, giving 50% modification at 30 min and 22-25% modification
      at 2 h after administration. A dose of 70 mg kg-1 BW12C administered 30 min
      before irradiation protected animals against lethality, and increased the
      radiation LD50 (95% CL) from 7.16 (7.05-7.27) to 7.86 (7.70-8.02) Gy,
      representing a DMF of 1.1. In contrast the same drug dose and schedule did not
      alter normal marrow CFUs radiosensitivity at doses up to 6 Gy. The dose of 70 mg
      kg-1 did, however, cause marked radioprotection in RIF-1 intramuscular leg
      tumours. Four- to seven-fold increases in survival were measured by clonogenic
      cell survival immediately or 24 h after treatment. Protection was maximal 15 to
      30 min after administration, and absent by 2 h. The drug did not protect RIF-1
      cells in culture against radiation damage, indicating that the in vivo effect is
      indirect. BW12C is therefore an effective tumour radioprotector in this tumour
      model, in a manner consistent with an increase in tumour hypoxic fraction,
      although factors other than changes in blood chemistry may also be involved.

PMID- 1345935
TI  - Single-strand break disappearance in quiescent and phytohaemagglutinin-stimulated
      human peripheral blood lymphocytes exposed to a single low dose of gamma
      radiation.
AB  - Quiescent and phytohaemagglutinin (PHA)-stimulated human peripheral blood
      lymphocytes (PBL) were irradiated with 4 Gy of gamma-rays and assayed using the
      alkaline filter elution technique to determine (1) the rate of removal of single
      strand breaks (ssb) and (2) the occurrence of excision repair events as indicated
      by the accumulation of ssb in the presence of the excision repair inhibitor 1
      beta-D-arabinofuranosylcytosine (araC). The percentage of ssb disappearance, in
      the absence of araC, at 5 min after irradiation was significantly higher in PHA
      stimulated PBL than in quiescent PBL [40.4 +/- 8.4% (mean +/- SD) and 71.3 +/-
      6.8% in quiescent and PHA-stimulated PBL, respectively]. In the presence of araC,
      both quiescent and PHA-stimulated PBL rapidly accumulated araC-associated ssb,
      indicating the inhibition of early (base excision) repair processes acting on
      alkali-stable base damages. Results with PBL from two different donors indicated
      a significantly higher rate of accumulation of araC-associated ssb in PHA
      stimulated PBL than in quiescent cells. In PBL from a third donor no such
      difference in the rate of accumulation of araC sites was observed. After 1 h
      repair incubation, the same number of araC-associated ssb was found in the two
      different cell populations from all three donors.

PMID- 1345936
TI  - External Ca(2+)-independent release of neurotransmitters.

PMID- 1345937
TI  - Depression by sodium ions of calcium uptake mediated by non-N-methyl-D-aspartate
      receptors in cultured cerebellar neurons and correlation with evoked D
      [3H]aspartate release.
AB  - In a previous study we noted that the release of D-[3H]aspartate evoked by non-N
      methyl-D-aspartate (non-NMDA) receptor agonists in cultured rat cerebellar
      granule cells was enhanced in the absence of extracellular Na+. To explain this
      apparent paradox, we tried in the present investigation to correlate the effect
      of Na+ removal on the kainate (KA)- and quisqualate (QA)-induced D-[3H]aspartate
      release with that on KA- and QA-induced 45Ca2+ accumulation. The releasing
      activity of KA, which was only partially Ca2+ dependent in the presence of Na+,
      became totally Ca2+ dependent in its absence. Moreover, the releasing activity of
      QA, which was Ca2+ independent in the presence of Na+, became 50% Ca2+ dependent
      in the absence of the monovalent cation. The releasing action of both agonists
      was in all cases antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and
      that induced by KA was also sensitive to kynurenic acid. When glutamate was
      tested as an agonist in the presence of Na+, it was found that its D
      [3H]aspartate releasing action was Ca2+ independent and was largely due to
      heteroexchange. The evoked release was Ca2+ independent, scarcely sensitive to
      CNQX, and insensitive to NMDA antagonists. In Na(+)-free medium, the glutamate
      evoked D-[3H]aspartate release was lower (due to the abolishment of
      heteroexchange), but was totally Ca2+ dependent and antagonized by CNQX and
      kynurenate. KA (30 microM-1 mM) stimulated the accumulation of 45Ca2+ in a dose
      dependent and CNQX-sensitive way, the effect being progressively higher as the
      Na+ concentration in the medium was decreased. Li+ affected KA-induced 45Ca2+
      accumulation in a way similar to Na+, although 45Ca2+ uptake was somewhat lower
      in Li(+)-containing medium. The voltage-activated calcium channel antagonists
      La3+ and (-)-202-791 caused only a limited inhibition of the KA-induced 45Ca2+
      influx both in the presence and in the absence of Na+. Under all the conditions
      tested [presence and absence of Na+ and of (-)-202-791], the kainate-induced
      45Ca2+ uptake was scarcely sensitive to the NMDA antagonist 2-amino-5
      phosphonovalerate. QA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid also stimulated 45Ca2+ influx in a CNQX-sensitive way, the effect being
      enhanced in Na(+)-free media. These agonists were, however, less effective than
      KA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1345938
TI  - Expression of the neuronal surface glycoprotein Thy-1 does not follow appearance
      of its mRNA in developing mouse Purkinje cells.
AB  - In developing rodent nervous system, although the appearance of Thy-1 mRNA, as
      seen by in situ hybridisation, is in general quickly followed by the appearance
      of immunohistochemically detectable protein, there are certain sites where a
      delay of several days occurs between expression of detectable message and
      protein. Mouse Purkinje cells exemplify this behaviour and are the dominant Thy-1
      expressing cell in early postnatal cerebellum, so allowing quantitative,
      homogenate-based methods to be used to test whether such a lag in protein
      expression does occur. Measurement of Thy-1 mRNA (by slot blot) and protein (by
      radioimmunoassay) shows a substantial excess of Thy-1 message, compared to
      protein accumulating in the tissue, during the first postnatal week, which is not
      found in tissues (rat cerebellum, and rat or mouse cerebrum) where no lag is
      apparent in appearance of Thy-1 protein from the section-based methods. The
      species of Thy-1 mRNA produced by Purkinje cells does not appear to change during
      development, as assessed either in terms of its size (by northern blotting) or in
      the heterogeneous pattern of transcription initiation sites used (assessed by S1
      nuclease protection analysis). Appearance of Thy-1 protein in these cells,
      therefore, seems to be regulated posttranscriptionally.

PMID- 1345939
TI  - Coordinate regulation of the cyclic AMP system with firing rate and expression of
      tyrosine hydroxylase in the rat locus coeruleus: effects of chronic stress and
      drug treatments.
AB  - Recent studies have demonstrated that chronic stress increases the firing rate
      and expression of tyrosine hydroxylase (TH) in neurons of the locus coeruleus
      (LC), the major noradrenergic nucleus in brain. The present study was undertaken
      to examine the influence of chronic stress and other treatments known to
      influence the activity of LC neurons on the cyclic AMP (cAMP) second messenger
      system in these neurons. Chronic (5 days) cold exposure significantly increased
      levels of TH immunoreactivity in the LC, as previously reported, but not in
      substantia nigra (SN) or ventral tegmentum (VT), two dopaminergic nuclei studied
      for comparison. Chronic cold exposure increased levels of cAMP-dependent protein
      kinase activity in soluble, but not particulate, fractions of the LC, and
      increased basal and GTP- and forskolin-stimulated adenylate cyclase activity in
      this brain region. In contrast, levels of the protein kinase and adenylate
      cyclase in VT, SN, and frontal cortex were not significantly influenced by cold
      exposure. To study further the relationship between regulation of LC firing rate,
      TH expression, and the cAMP system in the LC, other treatments known to influence
      TH were examined. Reserpine treatment, shown previously to increase levels of TH,
      was found to increase both LC firing rate and levels of soluble cAMP-dependent
      protein kinase activity in the LC. 6-Hydroxydopamine, shown previously to
      increase levels of TH and firing rate of LC neurons, also increased soluble
      levels of protein kinase activity. Other treatments known to either increase
      (adrenalectomy) or decrease (chronic imipramine) levels of TH in the LC were also
      found to increase or decrease, respectively, levels of cAMP-dependent protein
      kinase activity in this brain region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345940
TI  - Blood-brain barrier pericytes are the main source of gamma-glutamyltranspeptidase
      activity in brain capillaries.
AB  - Cerebral endothelial cells form the selective permeability barrier between brain
      and blood by virtue of their impermeable tight junctions and the presence of
      specific carrier systems. These specialized properties of brain capillaries are
      reflected in the presence of proteins that are not found in other capillaries of
      the body. gamma-Glutamyltranspeptidase (GGT) has been widely used as a marker for
      brain capillaries and differentiated properties of brain endothelial cells. By
      using histochemical and biochemical methods we have investigated the expression
      of GGT in isolated capillaries, cultured brain endothelial cells and pericytes,
      and cocultures of astrocytes and brain endothelial cells. It was surprising that
      the majority of GGT activity was associated with pericytes, but not endothelial
      cells, suggesting that GGT is a specific marker for brain pericytes. The
      remaining GGT activity that was associated with endothelial cells rapidly
      disappeared from cultured cells but was reinduced in cocultures with astrocytes.
      Our results emphasize the need for pure endothelial cells for the investigation
      of blood-brain barrier characteristics.

PMID- 1345941
TI  - Role of the central adrenergic system in the regulation of prostaglandin
      biosynthesis in rat brain.
AB  - The role of endogenous catecholamines in the regulation of brain prostaglandin
      (PG) synthesis was studied in the rat. Male rats were injected in the brain
      lateral ventricle or in the ventral noradrenergic bundle with either the
      catecholaminergic neurotoxin 6-hydroxydopamine or vehicle. Other groups of rats
      were injected intraperitoneally with the tyrosine hydroxylase inhibitor, alpha
      methyl-p-tyrosine, or with the inhibitor of dopamine-beta-hydroxylase, FLA-63.
      All these drugs produced a significant depletion of norepinephrine (NE) content
      in the cortex and hypothalamus. The rats that had lower levels of NE exhibited
      reduced capacity to synthesize PGE2 but not thromboxane B2 and 6-keto-PGE1 alpha
      in the cortex and hypothalamus. However, induced production of PG, stimulated by
      the bacterial endotoxin lipopolysaccharide (LPS), remained unchanged, namely, a
      similar (2- to 2.5-fold) increase of PG synthesis was noted in control and in NE
      depleted rats. We suggest that the regulation of PG synthesis under basal
      condition requires intact adrenergic input, whereas LPS-induced production of PG
      is independent of the adrenergic innervation.

PMID- 1345942
TI  - Synapsin I regulates glutamate release from rat brain synaptosomes.
AB  - Introduction of the dephosphorylated from of synapsin I into rat brain
      synaptosomes using freeze-thaw (transient) permeabilization significantly
      decreased the K(+)-induced release of glutamate. In contrast, introduction of
      synapsin I that had been phosphorylated by Ca2+/calmodulin-dependent protein
      kinase II was without effect on glutamate release. Addition of dephosphosynapsin
      I after freeze-thaw treatment also had no effect. Thus, the action of synapsin I
      was dependent on the phosphorylation state of synapsin I and on its entry into
      the synaptosomes. Our results implicate synapsin I as an important component in
      the regulation of neurotransmitter release in the mammalian nervous system.

PMID- 1345943
TI  - Kappa-opioids decrease excitatory transmission in the dentate gyrus of the guinea
      pig hippocampus.
AB  - In the guinea pig hippocampus, kappa 1-opioid binding sites were primarily
      localized in the molecular layer of the dentate gyrus as shown by autoradiography
      using either the kappa 1-selective radioligand 3H-U69,593 or the nonselective
      radioligand 3H-diprenorphine in the presence of unlabeled mu- and delta-blocking
      ligands. In this region, the electrophysiological effects of kappa 1-receptor
      activation were identified using extracellular and intracellular recordings of
      dentate granule cell responses. The amplitude of the extracellularly recorded
      population spike was reduced by U69,593 with an EC50 of 26 nM; this effect was
      reversible and blocked by the opioid antagonist naloxone. The kappa 1-selective
      antagonist norbinaltorphimine also blocked the effect of U69,593 with an apparent
      equilibrium dissociation constant (Ki) of 0.26 nM determined by Schild analysis
      in the physiologic assay. This value agreed well with the Ki for
      norbinaltorphimine at kappa 1-binding sites measured by radioligand binding
      displacement (0.24 nM). These results indicate that the electrophysiologic
      response observed was likely mediated by kappa 1-receptors. As seen with U69,593,
      dynorphin B, an endogenous opioid peptide that is present in the dentate gyrus,
      also inhibited the population spike response. mu- and delta-selective opioid
      agonists had no effect on the amplitude of the maximally evoked response.
      Intracellular recordings of dentate granule cells showed no direct effects of
      U69,593 on the granule cells themselves. However, analysis of synaptic potentials
      revealed that U69,593 significantly reduced the amplitude of glutaminergic EPSPs
      evoked by afferent stimulation without affecting IPSP amplitudes. The specific
      effect of U69,593 application on granule cell EPSPs indicates that presynaptic
      kappa 1-receptor activation inhibits glutamate release from perforant path
      terminals in the molecular layer of the dentate gyrus. These results suggest that
      endogenous dynorphins present in the granule cells may act as feedback inhibitors
      of the major excitatory input to the dentate gyrus.

PMID- 1345945
TI  - The NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5) impairs
      spatial learning and LTP in vivo at intracerebral concentrations comparable to
      those that block LTP in vitro.
AB  - This series of experiments investigated whether the NMDA receptor antagonist D-2
      amino-5-phosphonopentanoate (D-AP5) could induce impairments of spatial learning
      across a dose range comparable to its impairment of hippocampal long-term
      potentiation (LTP) in vivo. Estimations of the extracellular concentration of D
      AP5 in hippocampus using microdialysis were also made to compare whether these
      impairments occur at concentrations similar to those required to impair LTP in
      the in vitro hippocampal slice. Rats were chronically infused with D-AP5 into the
      lateral ventricle at a range of concentrations (0-50 mM) via osmotic minipumps.
      They were first trained to find and escape onto a hidden platform in an open
      field water maze task. After the behavioral learning, they were anesthetized with
      urethane and an attempt was made to evoke and monitor hippocampal LTP.
      Extracellular samples of D-AP5 in hippocampus were then taken using
      microdialysis, and finally, the animals were killed and tissue samples dissected.
      The microdialysis and tissue samples were analyzed for D-AP5 content using HPLC
      with fluorescence detection. The results established, first, that D-AP5 impairs
      spatial learning in a linear dose-dependent manner, highly correlated with its
      corresponding impairment of hippocampal LTP in vivo. No concentration of D-AP5
      was observed to block LTP without affecting learning. Second, the microdialysis
      estimates indicated that, subject to certain assumptions, D-AP5 causes these
      impairments at extracellular concentrations comparable to those that impair LTP
      in vitro. Third, comparison of the whole tissue and microdialysis samples
      revealed a concentration ratio of approximately 30:1, indicating that 97% of the
      intracerebral D-AP5 is inaccessible to the dialysis probes. Infusion of 20 mM
      EGTA was found to cause a sevenfold increase in D-AP5 in the dialysis perfusates,
      suggesting that at least part of the inaccessible D-AP5 is trapped by a calcium
      dependent mechanism. Two further behavioral control studies indicated that the D
      AP5-induced impairment of spatial learning is unlikely to be secondary to a drug
      induced motor disturbance, and that the performance of the D-AP5 group whose
      concentration was just sufficient to block hippocampal LTP completely was
      statistically indistinguishable from that of a group of rats with bilateral
      hippocampal lesions induced by ibotenic acid. Taken together, these findings
      offer support for the hypothesis that activation of NMDA receptors is necessary
      for certain kinds of learning.

PMID- 1345946
TI  - Glutamate uptake disguises neurotoxic potency of glutamate agonists in cerebral
      cortex in dissociated cell culture.
AB  - The pharmacological properties of glutamate agonists were compared in astrocyte
      rich and astrocyte-poor cultures derived from embryonic rat cerebral cortex. The
      object of this investigation was to determine the extent to which glutamate
      uptake might influence the receptor-mediated neurotoxic actions of these
      compounds. In astrocyte-rich cultures, using 30 min exposures, we observed that
      the potencies of the poorly transported agonists NMDA (35 microM) and D-glutamate
      (89 microM) were higher than that of L-glutamate (205 microM). In astrocyte-poor
      cultures, L-glutamate was much more potent, with an EC50 of 5 +/- 4 microM (3-12
      microM), for a 30 min exposure, whereas the potencies of NMDA and D-glutamate
      were essentially unchanged. L- and D-aspartate were also more effective in
      astrocyte-poor cultures, again with EC50 values of approximately 6-10 microM, as
      compared with 130 and 108 microM, respectively, in astrocyte-rich cultures. In
      other experiments, blocking sodium-dependent glutamate uptake in astrocyte-rich
      cultures, by using a sodium-free medium, made glutamate as potent an agonist as
      in astrocyte-poor cultures. Finally, we directly assessed the glutamate uptake
      system in astrocyte-rich and astrocyte-poor cultures and found that uptake was
      reduced approximately 25-fold in the astrocyte-poor cultures. These results show
      that in the presence of abundant astrocytes the neurotoxic potencies of L
      glutamate, L-aspartate, and D-aspartate are substantially under-estimated.

PMID- 1345944
TI  - Differential effects of neurotrophic factors on neurotransmitter development in
      the IMR-32 human neuroblastoma cell line.
AB  - The human neuroblastoma cell line IMR-32 exhibits both cholinergic and adrenergic
      properties. We have used IMR-32 cells to study the effects of CDF (CAT
      development factor) and bFGF (basic fibroblast growth factor) on the development
      of neurotransmitter properties. CDF treatment increases CAT activity in a dose
      dependent manner, independent of cell density. Time course studies show that
      there is a threefold increase in the specific CAT activity in IMR-32 cells
      treated with CDF for 6 d. CDF does not, however, affect the level of tyrosine
      hydroxylase (TH) activity, or the rate of cell proliferation. bFGF, on the other
      hand, induces TH activity and decreases CAT activity in a dose-dependent manner.
      bFGF's effect on TH is enhanced by increasing cell density, while its reduction
      of specific CAT activity is independent of cell density. Time course studies show
      a 30-fold increase in TH activity per cell and a threefold decrease in CAT
      activity per cell, after treatment with bFGF for 6 d. In contrast to the effects
      of CDF, bFGF enhances cell proliferation in IMR-32 cells. Double-labeled
      immunofluorescence studies showed that 95% of the cells stain for CAT and 65%
      stain for TH following treatment with CDF and bFGF, respectively. When these
      factors are combined, approximately 75% of the cells express both CAT and TH,
      demonstrating that IMR-32 cells are bipotential with regard to neurotransmitter
      associated enzyme expression. We also show that insulin-like growth factor I and
      NGF selectively induce CAT activity and cell proliferation, respectively, whereas
      epidermal growth factor has no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1345947
TI  - Regulation of hepatic lipogenic enzyme gene expression by diet quantity in rats
      fed a fat-free, high carbohydrate diet.
AB  - This investigation concerns the effects of the level of intake of a high
      carbohydrate diet on transcriptional rate, mRNA concentration and enzyme
      induction for lipogenic enzymes in rat liver. Six hours after refeeding fasted
      rats, the transcriptional rates in livers reached low maximum levels with small
      quantities of diet, but the mRNA concentrations continued to increase as diet
      intake increased. Greater diet intake primarily increased transcriptional rates
      and mRNA concentrations of lipogenic enzymes. After refeeding for 16 h, the mRNA
      concentrations were sigmoidly increased relative to the diet quantity and reached
      maximum levels of 20-, 110-, 22- and 16-fold above each fasted level for acetyl
      CoA carboxylase, fatty acid synthase, malic enzyme and glucose-6-phosphate
      dehydrogenase, respectively. After 3 d of refeeding (in a steady state of
      lipogenic enzyme activities), however, the transcriptional rates, mRNA
      concentrations and activity inductions of all the enzymes were sigmoidly
      increased relative to diet quantity, but were not different among the enzymes.
      Consequently, fatty acid synthesis and triglyceride levels in the liver were not
      increased by feeding less than 70% of ad libitum intake but were greatly
      increased by feeding greater than 70% of ad libitum intake.

PMID- 1345948
TI  - A novel method of induced renal hypothermia.
AB  - When the kidney is removed from cold storage for implantation into the recipient
      it gradually rewarms (second warm ischaemic time) and a prolonged second warm
      ischaemic time is a risk factor for delayed graft function. A cooling jacket has
      been designed to prevent this rewarming during transplantation. This study
      evaluates the efficacy of this device. Surface and core temperatures of less than
      15 degrees Centigrade were maintained for 120 minutes. Renal function was
      significantly better in cooled than in uncooled kidneys in a single kidney canine
      model. Induced renal hypothermia, using a device such as this, should be a
      routine manoeuvre in renal transplantation.

PMID- 1345949
TI  - The effects of an LHRH agonist on testicular function in the cryptorchid rat.
AB  - To assess the effects of an LHRH analog (LHRH-ethylamide des gly10 D-Leu6) on the
      function of the cryptorchid testis, an animal model was created, using
      prepubertal male Sprague-Dawley rats (21 days old). The animals were divided into
      six groups: 1) sham operated; 2) sham + LHRH treated; 3) cryptorchid; 4)
      cryptorchid + LHRH treated; 5) cryptorchid and orchidopexed; 6) cryptorchid, LHRH
      treated and orchidopexed. Two weeks post cryptorchidism, the animals were treated
      with either saline or LHRH-analog (one microgram./rat/day) subcutaneously for a
      total of twenty five days. Orchidopexy was performed following hormonal
      treatment. The effects of treatment were assessed in terms of body and
      reproductive organ weights, serum testosterone and LH levels, sperm counts and
      motility and fertility. The results demonstrated that experimental cryptorchidism
      impaired reproductive function, which was restored by orchidopexy, alone.
      Treatment of cryptorchid rats (groups 4 and 6) with LHRH did not produce any
      lasting improvement in spermatogenesis or fertility.

PMID- 1345950
TI  - Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune
      therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths
      among 75,000 women. Early Breast Cancer Trialists' Collaborative Group.
AB  - In a worldwide collaboration, information was sought and centrally checked on
      mortality and recurrence for each woman in any randomised trial that began before
      1985 of any aspect of systemic adjuvant therapy for early breast cancer. Checked
      data were available for 75,000 women (about 90% of those ever randomised), of
      whom 32% had died and another 10% had experienced recurrence. The parts now
      reviewed include 30,000 women in tamoxifen trials, 3000 in ovarian ablation
      trials, 11,000 in polychemotherapy trials, 15,000 in other chemotherapy
      comparisons, and 6000 in immunotherapy trials. Highly significant reductions in
      the annual rates both of recurrence and of death are produced by tamoxifen (25%
      SD 2 recurrence and 17% SD 2 mortality: 2p less than 0.00001), by ablation below
      age 50 (26% SD 6 recurrence and 25% SD 7 mortality: 2p = 0.0004), and by
      polychemotherapy (28% SD 3 recurrence and 16% SD 3 mortality: 2p less than
      0.00001), but not by ablation at older ages or by immunotherapy. (Tamoxifen also
      reduced the risk of development of contralateral breast cancer by 39% SD 9: 1p
      less than 0.00001). For tamoxifen and for polychemotherapy the avoidance of
      recurrence is chiefly during years 0-4 (this difference being maintained but not
      increased afterwards), but the avoidance of mortality is highly significant both
      during and after years 0-4, so the cumulative differences in survival produced by
      these relatively brief treatments (median: 2 years tamoxifen, 1 year
      polychemotherapy) are larger at 10 than at 5 years. There is little information
      beyond year 10 (except for ovarian ablation, which produces separately
      significant mortality reductions both during and after years 0-9). Both direct
      and indirect randomised comparisons show long-term polychemotherapy (eg, 12
      months) to be no better than shorter (eg, 6 months) regimens, but do show
      polychemotherapy to be significantly better than single-agent chemotherapy.
      Indirect randomised comparisons do not reveal significant differences between
      different forms of polychemotherapy, or differences between different tamoxifen
      doses, but do show that long-term tamoxifen (eg, 2 years, or even 5 years) is
      significantly more effective than shorter tamoxifen regimens. In old age (70+)
      tamoxifen is of demonstrated efficacy, but chemotherapy has not been evaluated.
      Between ages 50 and 69 direct comparisons show that chemotherapy plus tamoxifen
      is better (1p less than 0.00001) than chemotherapy alone both for recurrence and
      for mortality, and better (1p less than 0.00001) than tamoxifen alone for
      recurrence.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1345951
TI  - HIV-1 sensitivity to zidovudine and clinical outcome in children.
AB  - In adults with the acquired immunodeficiency syndrome, long-term monotherapy with
      zidovudine selects for human immunodeficiency virus type 1 (HIV-1) strains with
      substantially reduced in-vitro susceptibility to the drug. We have assessed the
      relation between in-vitro resistance to zidovudine and clinical outcome in
      children, in whom disease progression is more rapid than in adults. We studied 23
      children with symptoms of HIV-1 disease during extended monotherapy with
      zidovudine. An in-vitro assay was used to determine the concentration of
      zidovudine required to inhibit by 50% the replication of viral isolates (IC50)
      obtained after 9 to 39 months of treatment. Viral stocks of high enough titre to
      yield reproducible results were obtained from 19 of the children. During the
      following 6 months of therapy, 9 children were stable, 7 deteriorated, and 3
      died. There was a highly significant relation between decreased zidovudine
      susceptibility and poor clinical outcome (p less than 0.001) but no relation
      between IC50 and age at start of therapy or length of time on treatment. Age
      adjusted CD4 lymphocyte counts were lower at the start of treatment (p = 0.02)
      and at the time of sampling (p = 0.01) in children whose viral isolates had an
      increased zidovudine IC50. Initial serum p24 antigen levels were not predictive
      of subsequent emergence of resistant virus, but at the time of sampling for viral
      sensitivity higher p24 antigen levels were associated with raised IC50 (p =
      0.004). The findings suggest that most children who become unresponsive to
      monotherapy with zidovudine, as judged by clinical criteria, will have changes in
      in-vitro sensitivity to the drug. In these children, an alternative
      antiretroviral therapy should be considered.

PMID- 1345952
TI  - Coagulation-factor deficiencies and abnormal bleeding in Noonan's syndrome.
AB  - Noonan's syndrome is characterised by a dysmorphic facies, congenital heart
      disease, and short stature, and is inherited as an autosomal dominant trait.
      Because abnormal bleeding has also been reported, we investigated a group of
      patients for coagulation-factor deficits. Of the 72 individuals studied (37 male,
      35 female, mean age 11.4 years), 47 (65%) had a history of abnormal bruising or
      bleeding. 29 patients (40%) had a prolonged activated partial thromboplastin
      time. Specific abnormalities in the intrinsic pathway of coagulation (partial
      factor XI:C, XII:C, and VIII:C deficiencies) were found in 36 patients (50%).
      Multiple abnormalities among these 36 patients included combined factor XI:C and
      XII:C deficiencies (4 patients) and factor XI:C and VIII:C deficiencies (4), and
      1 patient had combined factor VIII:C, XI:C, and XII:C deficiency. There was poor
      correlation between a history of abnormal bleeding and coagulation-factor
      deficit. In five families, similar coagulation-factor deficiencies were present
      in first-degree relatives with the syndrome. The pattern of inherited bleeding
      abnormalities seen in Noonan's syndrome suggests autosomal regulation of the
      intrinsic coagulation pathway.

PMID- 1345953
TI  - Platelet-derived growth factor BB for the treatment of chronic pressure ulcers.
AB  - A randomised, phase I/II, double-blind, placebo-controlled study was designed to
      assess the effect of topically applied recombinant human BB homodimeric platelet
      derived growth factor (rPDGF-BB) on healing of chronic pressure ulcers. Twenty
      patients were randomly allocated daily treatment for 28 days with 1, 10, or 100
      micrograms/ml rPDGF-BB (0.01, 0.1, or 1.0 micrograms per cm2 ulcer area) or
      placebo. Patients treated with 100 micrograms/ml rPDGF-BB showed a greater
      healing response than the placebo group, but the lower doses had little effect.
      After 28 days, ulcers treated with 100 micrograms/ml rPDGF-BB were smaller than
      those treated with placebo (mean [SE] volume 6.4 [4.0] vs 21.8 [5.6]% of day 0
      volume). There were no toxic effects. These preliminary findings suggest that
      rPDGF-BB is a potent wound-healing agent in soft tissue.

PMID- 1345954
TI  - Abnormal sulphur oxidation in systemic lupus erythematosus.
AB  - S-carboxy-L-methylcysteine was used to assess the activity of the S-oxidation
      pathway of sulphur metabolism in 35 patients with systemic lupus erythematosus
      (SLE); 25 (71%) showed impaired sulphoxidation and 21 (60%) produced virtually no
      sulphoxides, compared with 17 (36%) and 2 (4%), respectively, of 47 healthy
      controls. The substrate/product ratio of cysteine oxygenase (plasma
      cysteine/sulphate) was significantly higher in SLE patients than in controls
      (median [interquartile range] 362 [224-588] vs 65 [44-111]; p less than 0.00001).
      The alternative pathway of sulphur metabolism, S-methylation, catalysed by
      thiolmethyltransferase, was not impaired in the SLE patients. There is a
      biochemical difference in sulphur metabolism between SLE and rheumatoid
      arthritis, since both pathways are impaired in the latter disorder.

PMID- 1345955
TI  - Adjuvant systemic therapy for early breast cancer.

PMID- 1345956
TI  - Hypertension--in black and white.

PMID- 1345957
TI  - Gold standard for the GFR?

PMID- 1345958
TI  - Preoxygenation: physiology and practice.

PMID- 1345959
TI  - Nursing research matters.

PMID- 1345960
TI  - Assessment of bullet disruption in armed conflicts.
AB  - Under international humanitarian law, the Hague Declaration of 1899 forbids the
      use of small arms ammunition that disrupts in the body after impact. However,
      assessment of whether bullets have undergone disruption is subjective and
      accusations that one or both sides of a conflict have used such ammunition cannot
      be substantiated. We describe a method by which disruption of bullets after
      impact can be assessed objectively. We reviewed 1287 wound radiographs of 1201
      patients in four International Committee of the Red Cross hospitals. Radiographs
      were scored according to the F (fracture) and M (presence of metallic bodies)
      variables of the Red Cross wound classification; bullet disruption is evidenced
      by metallic fragments on the radiograph. One hospital had a significantly higher
      proportion of patients wounded by bullets that disrupted after impact; these
      wounds were associated with comminuted fractures. The findings show that the
      presence of metallic fragments on a radiograph is a reliable indicator of wound
      severity and bullet disruption. The study has important implications for the
      upholding of international humanitarian law, because with our method the use and
      manufacture of bullets that contravene the Hague Declaration can be identified.

PMID- 1345961
TI  - Allogeneic bone-marrow transplantation without protective isolation in adults
      with malignant disease.
AB  - Bone-marrow transplant (BMT) patients are severely immunocompromised immediately
      after the procedure and they are commonly nursed in strict protective isolation
      to reduce the risk of both infection and graft-versus-host disease (GvHD). We
      have studied a consecutive series of patients to see whether protective isolation
      is of benefit as prophylaxis against infectious complications of BMT. 50
      consecutive patients who had malignant disease and received their first BMT from
      siblings or unrelated donors were nursed in standard single rooms with visitors
      instructed to wash their hands. A subset of 20 patients living locally spent a
      median of 25 days in hospital after BMT; they also spent some time at home on a
      median of 8 days before engraftment and 3 patients went home on more than 90% of
      their hospital days. 16 patients (32%) had positive bacterial cultures and/or
      focal infection. Gram-positive bacteraemia was found in 12 subjects (24%) but
      there were no gram-negative or deep fungal infections. Grade II or III acute GvHD
      developed in 17 patients (34%). There were no deaths from infection or acute
      GvHD. Transplant-related mortality was 6% in the first 100 days and 18% overall
      with a median follow-up of 22 months. Our mortality data compare favourably with
      those from institutions with strict isolation procedures. We conclude that BMT
      may be safely completed in some institutions without either protective isolation
      or the need to confine patients continuously in hospital.

PMID- 1345962
TI  - Physicians, elderly drivers, and dementia.
AB  - In western countries, the proportion of drivers who are elderly is increasing
      rapidly; over a quarter of the driving population will be 55 years of age or
      older by the year 2000. Although elderly drivers tend to drive less and may avoid
      night driving, the number of car accidents and the severity of injuries sustained
      in such accidents by distance driven increases strikingly after the age of 65.
      But how can doctors identify those elderly drivers who are a danger to themselves
      and others? And, once they are identified, how should clinicians balance the
      effects of removing a driving licence, which may greatly affect a patient's
      lifestyle, against public safety and breach of confidentiality if the patient
      refuses to give up his or her licence voluntarily? Medical decisions about
      illnesses that predispose to loss of consciousness are fairly clear-cut, but
      normal ageing processes and dementia can be much more difficult to identify and
      to assess; moreover, there seems little correlation between tests of mental
      performance and driving ability. Comparisons between practices in different
      countries may provide some answers, but the introduction of modified driving
      tests for elderly drivers with some evidence of mild impairment but who wish to
      retain their driving licence should be considered.

PMID- 1345963
TI  - Breast cancer trials: a patient's viewpoint.

PMID- 1345964
TI  - Informed consent when an investigation is interrupted.

PMID- 1345965
TI  - Eradicating Helicobacter pylori.

PMID- 1345966
TI  - Eradicating Helicobacter pylori.

PMID- 1345967
TI  - Eradicating Helicobacter pylori.

PMID- 1345968
TI  - Eradicating Helicobacter pylori.

PMID- 1345969
TI  - Pruritus as presenting sign of cervical rib.

PMID- 1345970
TI  - Mupirocin resistance.

PMID- 1345971
TI  - Mupirocin resistance.

PMID- 1345972
TI  - Smoking and CHD in women.

PMID- 1345973
TI  - Triazolam and PAF inhibition.

PMID- 1345974
TI  - Triazolam and PAF inhibition.

PMID- 1345975
TI  - Early detection of epidemic influenza.

PMID- 1345976
TI  - Cholesterol embolisation syndrome after thrombolytic therapy for myocardial
      infarction.

PMID- 1345977
TI  - Growth rates of breast tumours.

PMID- 1345978
TI  - Child heart donors.

PMID- 1345979
TI  - Health indicators in Yemen.

PMID- 1345980
TI  - US Patient Self-Determination Act.

PMID- 1345981
TI  - Patient referral and NHS reforms.

PMID- 1345982
TI  - Day-case surgery.

PMID- 1345983
TI  - Fall in deaths from respiratory disease.

PMID- 1345985
TI  - Indications for pacing.

PMID- 1345984
TI  - Recombinant factor VIII concentrate. The MSAC, Canadian Hemophilia Society.
      Canadian Hemophilia Clinic Directors Group.

PMID- 1345986
TI  - Chloroquine and proguanil prophylaxis in travellers to Kenya.

PMID- 1345987
TI  - Chloroquine and proguanil prophylaxis in travellers to Kenya.

PMID- 1345988
TI  - Chloroquine and proguanil prophylaxis in travellers to Kenya.

PMID- 1345989
TI  - Chloroquine and proguanil prophylaxis in travellers to Kenya.

PMID- 1345990
TI  - Twins with different fathers.

PMID- 1345991
TI  - Misoprostol to induce labour.

PMID- 1345992
TI  - Oral immunosuppression for multiple sclerosis.

PMID- 1345993
TI  - Diagnosis of urinary tract infection in children.

PMID- 1345994
TI  - Diagnosis of urinary tract infection in children.

PMID- 1345995
TI  - Neonatal bilirubin.

PMID- 1345996
TI  - Limb-reduction defects and chorionic villus sampling.

PMID- 1345997
TI  - Twinning among HIV-infected mothers.

PMID- 1345998
TI  - Weekend migraine in men.

PMID- 1345999
TI  - Diet, fasting, and rheumatoid arthritis.

PMID- 1346000
TI  - Prognostic indices in subarachnoid haemorrhage.

PMID- 1346001
TI  - Diet, fasting, and rheumatoid arthritis.

PMID- 1346002
TI  - Diet, fasting, and rheumatoid arthritis.

PMID- 1346003
TI  - Laryngeal mask airway in acute cerebrovascular disease.

PMID- 1346004
TI  - Drugs for childhood fever.

PMID- 1346005
TI  - Drugs for childhood fever.

PMID- 1346006
TI  - Drugs for childhood fever.

PMID- 1346007
TI  - Drugs for childhood fever.

PMID- 1346008
TI  - Efficacy of antibiotic prophylaxis for prevention of native-valve endocarditis.
AB  - Whether antibiotic prophylaxis can prevent bacterial endocarditis is hotly
      debated. In an attempt to settle this issue, we have assessed the efficacy of
      prophylaxis for bacterial endocarditis on native valves in a nationwide, case
      control study in the Netherlands. Cases were patients with known cardiac disease
      in whom endocarditis developed within 180 days of a medical or dental procedure
      for which prophylaxis was indicated. Of a total of 438 patients with endocarditis
      diagnosed during 2 years, 48 were eligible for the study. Controls were patients
      with the same cardiac status in whom endocarditis did not develop within 180 days
      of a similar procedure; of a total of 889 controls from five hospitals, 200 were
      eligible. Overall, about 1 in 6 patients in both groups had received prophylaxis.
      The best estimate of protective efficacy was 49% for first-ever endocarditis
      occurring within 30 days of a procedure. Endocarditis developed within 30 days of
      a procedure in only 13% of patients with a previously diagnosed heart lesion
      which predisposed to the disease. The findings suggest that strict adherence to
      generally accepted recommendations for prophylaxis might do little to decrease
      the total number of patients with endocarditis in the community.

PMID- 1346009
TI  - Loss of heterozygosity on chromosome 7q and aggressive primary breast cancer.
AB  - Genetic alterations are believed to be important in the origin and dissemination
      of breast cancer. Cytogenetic rearrangements on chromosome 7 are common in breast
      tumours. We used the c-met proto-oncogene probe, which detects sequences on
      chromosome 7q31, to analyse tumour and blood leucocyte DNA samples from 245
      patients with primary breast cancers. The pmetH polymorphic probe detected a high
      frequency of allele loss (40.5%) among the 121 informative (heterozygous)
      patients. This genetic alteration was not significantly associated with standard
      prognostic features including tumour size, histopathological grade, and lymph
      node or steroid receptor status. However, patients with loss of heterozygosity on
      chromosome 7q31 in primary tumour DNA had significantly shorter metastasis-free
      survival (p = 0.00022) and overall survival (p = 0.0036) after surgery than
      patients without this alteration. These findings indicate that this region of
      chromosome 7 might be the site of a breast tumour or metastasis suppressor gene.

PMID- 1346010
TI  - Colour Doppler ultrasound assessment of arteriovenous haemodialysis fistulas.
AB  - Satisfactory function of the arteriovenous fistula (AVF) is essential for
      adequate haemodialysis in patients with chronic renal failure. Existing methods
      to assess AVF function are imprecise (eg, clinical examination) or invasive (eg,
      angiography). We assessed the value of colour flow-doppler ultrasound (CFDU) in
      the investigation of clinically suspected AVF dysfunction. 51 patients with
      suspected impairment of AVF function were studied by CFDU, and 28 also underwent
      angiography. The findings were compared with the reference standard of the
      findings at reoperation. CFDU showed AVF stenoses in 18 patients, which were all
      confirmed at reoperation; the results of angiography in 13 of these 18 patients
      showed complete agreement with the findings of CFDU and surgery. CFDU showed
      partial or complete AVF thrombosis in 33 patients, confirmed in all patients at
      reoperation; 15 patients also underwent angiography, and thrombi were not found
      in 6 (in 4 because of technical failure). 7 patients had aneurysms on CFDU that
      were confirmed by surgery in all patients and by angiography in 2 of the 3
      patients studied. CFDU enables reliable non-invasive assessment of AVF morphology
      and function and may become the procedure of choice for AVF assessment in
      patients with suspected AVF abnormalities.

PMID- 1346011
TI  - Erythrocyte choline uptake after renal transplantation.
AB  - Erythrocyte membrane choline transport is abnormally high in chronic renal
      failure. The aim of this study was to find out whether, and how quickly, this
      abnormality is reversed by renal transplantation. Ten adults with chronic renal
      failure were studied before and for up to 6 months after renal transplantation.
      Plasma creatinine concentration and erythrocyte uptake of radiolabelled choline
      were measured periodically for up to 6 months. The maximum rate of choline
      transport (Vmax) was abnormally high before transplantation and fell to normal
      values during the first week after transplantation. This fall matched that in
      plasma creatinine. A temporary rise in plasma creatinine in one patient, reversed
      by methylprednisolone treatment, was accompanied by a rise in choline flux, and
      graft failure in another patient was accompanied by a return to pretreatment
      rates of choline transport. Thus, the high rates of choline uptake in uraemia are
      rapidly reduced on recovery of renal function. The speed of the changes suggests
      the involvement of a plasma factor.

PMID- 1346012
TI  - Ciprofloxacin for treatment of malakoplakia.
AB  - The tumour-like lesions of the rare disease malakoplakia, which consist of
      macrophages containing undigested coliform bacteria, are often misdiagnosed as a
      carcinoma. Although an infectious aetiology is likely, no antimicrobial therapy
      has been successful in the long-term. Since ciprofloxacin penetrates well into
      macrophages, this drug was given to two patients with advanced malakoplakia (500
      mg twice daily). After long-term treatment all granulomatous lesions disappeared.
      Thus, malakoplakia can be cured by antibiotic treatment.

PMID- 1346013
TI  - Idiopathic hemiparetic parkinsonism, a syndrome distinct from idiopathic
      parkinsonism.
AB  - Two women had a syndrome of progressive parkinsonism with ipsilateral rigidity,
      mild resting tremor, paresis, hyperreflexia, and an extensor plantar response.
      Symptoms had started 24 and 3 months after a surgical procedure in the affected
      limb. Neuroimaging studies were unhelpful. Both the parkinsonian features and the
      pyramidal tract signs responded well to dopaminergic drug treatment. We propose
      that the syndrome be called "idiopathic hemiparetic parkinsonism".

PMID- 1346014
TI  - Sumatriptan, serotonin, migraine, and money.

PMID- 1346015
TI  - Insights into fasting.

PMID- 1346016
TI  - Excess water administration and hyponatraemic convulsions in infancy.

PMID- 1346017
TI  - Thyroid dysfunction in utero.

PMID- 1346018
TI  - Biological basis of radiation therapy for cancer.

PMID- 1346019
TI  - Role of assays for parathyroid-hormone-related protein in investigation of
      hypercalcaemia.
AB  - Parathyroid-hormone-related protein (PTHrP) has been implicated as a humoral
      mediator of hypercalcaemia in malignant disease. We have investigated the
      contributions of PTHrP and parathyroid hormone (PTH) to the hypercalcaemia seen
      in routine clinical practice by means of highly sensitive immunoradiometric
      assays. PTHrP concentrations in plasma and PTH concentrations in serum were
      measured in 121 consecutive patients with hypercalcaemia (corrected serum calcium
      above 2.65 mmol/l) identified from routine biochemical profiles in a district
      general hospital. Hypercalcaemia was due to primary hyperparathyroidism in 63
      (52%) patients and to malignant disease in 40 (49%). Plasma PTHrP was detectable
      in 35 (88%) of 40 patients with solid tumours and 3 of 9 patients with
      haematological malignant disease; it was undetectable in 92% of patients with
      primary hyperparathyroidism. 7 patients with malignant disease had PTH
      concentrations above 4.0 pmol/l, consistent with coexisting primary
      hyperparathyroidism. Measurement of both PTH and PTHrP in all patients led to a
      change in the diagnosis in 7% of patients. This study provides direct evidence
      for a humoral role of tumour-derived PTHrP in hypercalcaemia, and shows how PTHrP
      assays can be used appropriately, in conjunction with PTH assays, to investigate
      hypercalcaemia in routine clinical practice.

PMID- 1346020
TI  - Diagnostic laparoscopic cholecystectomy.

PMID- 1346021
TI  - Too many medical beds?

PMID- 1346022
TI  - Legal status of dead "patients".

PMID- 1346023
TI  - WHO definition of tachypnoea in children.

PMID- 1346024
TI  - Chinese paralytic syndrome.

PMID- 1346025
TI  - PCR to identify CMV.

PMID- 1346026
TI  - Usefulness of bone-marrow biopsy during induction therapy for acute myeloid
      leukemia.

PMID- 1346027
TI  - Optic neuritis and myelitis after booster tetanus toxoid vaccination.

PMID- 1346028
TI  - Mucosal immunity to oral vaccines.

PMID- 1346029
TI  - Thalassaemia strategy in Sicily.

PMID- 1346030
TI  - Hepatic hamartoma in tuberous sclerosis.

PMID- 1346031
TI  - Prenatal cytogenetic and postnatal molecular studies on 46,XX male.

PMID- 1346032
TI  - Infectious complications of subcutaneous interleukin-2 and interferon-alpha.

PMID- 1346033
TI  - Antithrombin III and arterial disease.

PMID- 1346034
TI  - Dantrolene for exertional heatstroke.

PMID- 1346035
TI  - Fractals, chaos, and fetal heart rate.

PMID- 1346036
TI  - Elderly patients and chronic haemodialysis.

PMID- 1346037
TI  - Psychiatric diagnoses and disease.

PMID- 1346038
TI  - Psychiatric diagnoses and disease.

PMID- 1346039
TI  - Psychiatric diagnoses and diseases.

PMID- 1346040
TI  - Public survey of resource allocation preferences.

PMID- 1346041
TI  - Colour blindness and pathologists.

PMID- 1346042
TI  - Incentives for organ donation.

PMID- 1346043
TI  - Computer-based knowledge systems.

PMID- 1346044
TI  - Autism and asperger syndrome.

PMID- 1346045
TI  - Triazolam and platelet-aggregating factor.

PMID- 1346046
TI  - The J curve lives.

PMID- 1346047
TI  - Measurement of breath alcohol.

PMID- 1346048
TI  - Aspergillus antigen latex test for diagnosis of invasive aspergillosis.

PMID- 1346049
TI  - Rise in intracranial pressure with intravenous adenosine.

PMID- 1346050
TI  - Infantile spasms.

PMID- 1346051
TI  - Levodopa.

PMID- 1346052
TI  - Social care of children born to HIV-infected parents.

PMID- 1346053
TI  - Formulations of didanosine (ddI) and salt overload.

PMID- 1346054
TI  - Ribavirin aerosols and respiratory syncytial virus infection.

PMID- 1346055
TI  - Seropositivity for Legionella in Campylobacter infection.

PMID- 1346056
TI  - Omental milky spots.

PMID- 1346057
TI  - Trends in child growth from a single cross-sectional survey.

PMID- 1346058
TI  - Pseudomembranous colitis complicating chemotherapy.

PMID- 1346059
TI  - Fetal haemorrhagic lesions after chorionic villous sampling.

PMID- 1346060
TI  - Influenza vaccination in asthma.

PMID- 1346061
TI  - Tegernsee giant.

PMID- 1346062
TI  - Identification of replication factor C from Saccharomyces cerevisiae: a component
      of the leading-strand DNA replication complex.
AB  - A number of proteins have been isolated from human cells on the basis of their
      ability to support DNA replication in vitro of the simian virus 40 (SV40) origin
      of DNA replication. One such protein, replication factor C (RFC), functions with
      the proliferating cell nuclear antigen (PCNA), replication protein A (RPA), and
      DNA polymerase delta to synthesize the leading strand at a replication fork. To
      determine whether these proteins perform similar roles during replication of DNA
      from origins in cellular chromosomes, we have begun to characterize functionally
      homologous proteins from the yeast Saccharomyces cerevisiae. RFC from S.
      cerevisiae was purified by its ability to stimulate yeast DNA polymerase delta on
      a primed single-stranded DNA template in the presence of yeast PCNA and RPA. Like
      its human-cell counterpart, RFC from S. cerevisiae (scRFC) has an associated DNA
      activated ATPase activity as well as a primer-template, structure-specific DNA
      binding activity. By analogy with the phage T4 and SV40 DNA replication in vitro
      systems, the yeast RFC, PCNA, RPA, and DNA polymerase delta activities function
      together as a leading-strand DNA replication complex. Now that RFC from S.
      cerevisiae has been purified, all seven cellular factors previously shown to be
      required for SV40 DNA replication in vitro have been identified in S. cerevisiae.

PMID- 1346064
TI  - Extrathymic positive selection of alpha beta T-cell precursors in nude mice.
AB  - T lymphocytes expressing alpha beta T-cell receptors with sufficient affinity to
      major histocompatibility complex (MHC) molecules expressed on thymus epithelial
      cells are positively selected and mature to functional T cells. But several
      studies have demonstrated that athymic nude mice grafted with MHC-incompatible
      thymuses developed T cells specific for nude host rather than thymic MHC. We
      examined this paradox by analysing the specificity of T lymphocytes derived from
      nude mice. We report here that nude T lymphocyte precursors transferred to
      allogeneic SCID (severe combined immunodeficiency) mice with a functioning thymus
      (but lacking T or B cells) generated host MHC-restricted effector T cells but
      also contained T cells restricted to donor MHC. If nude T cells were depleted
      from nude lymphohaemopoietic donor cells before or after transfer, only host MHC
      specific T cells matured. The results may explain the unusual MHC specificities
      of nude T lymphocytes described in earlier studies and demonstrate two separate
      differentiation steps: in nude mice, T cells may be positively selected for self
      MHC restriction specificity extrathymically; then a functional thymus is required
      for efficient T cell maturation.

PMID- 1346063
TI  - Susceptibility to cell death is a dominant phenotype: triggering of activation
      driven T-cell death independent of the T-cell antigen receptor complex.
AB  - The failure of Thy-1 and Ly-6 to trigger interleukin-2 production in the absence
      of surface T-cell antigen receptor complex (TCR) expression has been interpreted
      to suggest that functional signalling via these phosphatidylinositol-linked
      alternative activation molecules is dependent on the TCR. We find, in contrast,
      that stimulation of T cells via Thy-1 or Ly-6 in the absence of TCR expression
      does trigger a biological response, the cell suicide process of activation-driven
      cell death. Activation-driven cell death is a process of physiological cell death
      that likely represents the mechanism of negative selection of T cells. The
      absence of the TCR further reveals that signalling leading to activation-driven
      cell death and to lymphokine production are distinct and dissociable. In turn,
      the ability of alternative activation molecules to function in the absence of the
      TCR raises another issue: why immature T cells, thymomas, and hybrids fail to
      undergo activation-driven cell death in response to stimulation via Thy-1 and Ly
      6. One possibility is that these activation molecules on immature T cells are
      defective. Alternatively, susceptibility to activation-driven cell death may be
      developmentally regulated by TCR-independent factors. We have explored these
      possibilities with somatic cell hybrids between mature and immature T cells, in
      which Thy-1 and Ly-6 are contributed exclusively by the immature partner. The
      hybrid cells exhibit sensitivity to activation-driven cell death triggered via
      Thy-1 and Ly-6. Thus, the Thy-1 and Ly-6 molecules of the immature T cells can
      function in a permissive environment. Moreover, with regard to susceptibility to
      Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive
      environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6
      triggering, the mature phenotype of sensitivity to cell death is genetically
      dominant.

PMID- 1346065
TI  - Molecular characterization and silk gland expression of Bombyx engrailed and
      invected genes.
AB  - Genetic analysis in Drosophila has shown that engrailed (en) plays an important
      role in segmentation and neurogenesis. A closely related gene, invected (in), is
      coexpressed with en in the posterior developmental compartments where en is known
      to specify cell state. We report here the isolation of two en-like cDNAs from the
      middle silk glands of Bombyx mori larvae. Sequence analysis revealed that they
      are the counterparts of Drosophila en and in. Four highly conserved domains,
      including the homeodomain, were identified in these En and In proteins from
      Bombyx and Drosophila. In addition, two en-specific and one in-specific domains
      could also be found. These structurally homologous genes might share a similar
      role in Bombyx development. They were found to be coexpressed in the middle silk
      gland but not in the posterior silk gland during the fourth molt/fifth intermolt
      period. We speculate that these Bombyx en-like genes might be involved in the
      compartmentalization of the silk gland.

PMID- 1346066
TI  - Selective killing of CD4+ cells harboring a human immunodeficiency virus
      inducible suicide gene prevents viral spread in an infected cell population.
AB  - We have stably expressed in CD4+ lymphoid cells the herpes simplex virus type 1
      thymidine kinase (HSV1-TK) gene under the control of the human immunodeficiency
      virus (HIV) promoter and transactivation response element sequences. Upon HIV
      infection these regulatory sequences were transactivated, switching on high-level
      expression of HSV1-TK. This in turn caused the death of HIV-infected cells when
      they were cultured in the presence of acyclovir, a nucleoside analog that becomes
      toxic after phosphorylation by HSV1-TK. The elimination of HIV-infected cells
      resulted in the arrest of HIV spreading in the culture. Complete protection of
      HSV1-TK-expressing cells was obtained using acyclovir concentrations that are
      commonly detected in the plasma of patients treated for HSV1 infection. Thus,
      expression of this DNA construct generates a pool of CD4+ booby-trapped cells
      that, as a population, are resistant to HIV infection. Our data provide a
      rationale for the use of suicide genes in the design of gene therapy of HIV
      infection.

PMID- 1346067
TI  - Long-distance restriction mapping of the proximal long arm of human chromosome 21
      with Not I linking clones.
AB  - Human chromosome 21 is the smallest of the 22 autosomes and 2 sex chromosomes.
      Hybridization of the human repetitive sequence Alu to pulsed-field gel
      fractionated Not I-digested genomic DNA from a human-mouse hybrid cell line
      containing chromosome 21 as the sole human component identified chromosome 21 Not
      I restriction fragments. A Not I restriction map of regions of the chromosome was
      constructed, by identifying neighboring Alu bands with Not I linking clones. This
      approach simplifies the task of physical mapping and avoids ambiguities in Not I
      fragment assignments that arise from gel-to-gel mobility variations. A contiguous
      map was constructed with six Not I linking clones that covers at least the
      proximal one-third of the long arm of chromosome 21 and spans 20 megabases. A
      more detailed restriction map revealed 11 likely CpG islands in this region and
      localized 11 additional DNA markers.

PMID- 1346068
TI  - Cloning and functional characterization of a family of human and mouse
      somatostatin receptors expressed in brain, gastrointestinal tract, and kidney.
AB  - Somatostatin is a tetradecapeptide that is widely distributed in the body. It
      acts on multiple organs including brain, pituitary, gut, exocrine and endocrine
      pancreas, adrenals, thyroid, and kidneys to inhibit release of many hormones and
      other secretory proteins. In addition, it functions as a neuropeptide affecting
      the electrical activity of neurons. Somatostatin exerts its biological effects by
      binding to specific high-affinity receptors, which appear in many cases to be
      coupled to GTP-binding proteins. Here we report the cloning, functional
      expression, and tissue distribution of two different somatostatin receptors
      (SSTRs). SSTR1 and SSTR2 contain 391 and 369 amino acids, respectively, and are
      members of the superfamily of receptors having seven transmembrane segments.
      There is 46% identity and 70% similarity between the amino acid sequences of
      SSTR1 and SSTR2. Stably transfected Chinese hamster ovary cells expressing SSTR1
      or SSTR2 exhibit specific somatostatin binding, with an apparently higher
      affinity for somatostatin-14 than somatostatin-28, and NH2-terminally extended
      form of somatostatin-14. RNA blotting studies show that SSTR1 and SSTR2 are
      expressed at highest levels in jejunum and stomach and in cerebrum and kidney,
      respectively. A SSTR1 probe hybridized to multiple DNA fragments in EcoRI digests
      of human and mouse DNA, indicating that SSTR1 and SSTR2 are members of a larger
      family of somatostatin receptors. Thus, the biological effects of somatostatin
      are mediated by a family of receptors that are expressed in a tissue-specific
      manner.

PMID- 1346069
TI  - Human immunodeficiency virus (HIV) type 1 can superinfect HIV-2-infected cells:
      pseudotype virions produced with expanded cellular host range.
AB  - In studies on viral interference, cloned T-cell lines chronically infected with
      human immunodeficiency virus (HIV) type 1 or HIV-2 were inoculated with several
      strains of these two AIDS retrovirus subtypes. HIV-2UC1-infected cells, which
      still express the CD4 receptor, could be superinfected with a variety of HIV-1
      and HIV-2 strains. This event was accompanied by cytopathic effects in the cells
      and production of pseudotype virions with an expanded cellular host range. HIV-1-
      or HIV-2-infected clonal cell lines, which did not express CD4, could not be
      superinfected by any HIV strains but were coinfected after transfection of
      molecular clones into the persistently infected cells. These observations
      indicate that viral interference with HIV occurs at the cell surface and involves
      a down-modulation of the CD4 molecule. If the CD4 protein is expressed,
      superinfection can take place, and phenotypically mixed virus particles are
      produced. Since HIV-1 and HIV-2 dually infected individuals have been detected,
      these in vitro observations may have relevance to the in vivo state.

PMID- 1346071
TI  - Depression of the Ca(2+)-ATPase activity of the rat liver endoplasmic reticulum
      by the liver tumour promoters, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane and
      phenobarbital.
AB  - The effects of a short-term in vivo administration of two liver tumour promoters
      (phenobarbital and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane on rat liver
      endoplasmic reticulum Ca(2+)-ATPase were investigated. The specific activity
      values of this membrane-bound enzyme significantly decreased (P less than 0.01)
      by 51% for phenobarbital-treated rats and by 48% for 1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane-treated rats compared with control animals. The depression of
      liver endoplasmic reticulum Ca(2+)-ATPase appears to be a manifestation of the
      toxicological effect of tumour promoters.

PMID- 1346072
TI  - Cytosolic long-chain acyl-CoA hydrolase, a suitable parameter to measure hepatic
      response to peroxisome proliferators.
AB  - The possibility of using cytosolic long-chain acyl-CoA as a parameter to measure
      the response of liver to peroxisome proliferators was studied. A subcutaneous
      (s.c.) injection of perfluorooctanoic acid (PFOA) to male Wistar rats caused an
      increase in activity of cytosolic long-chain acyl-CoA hydrolase. This increase in
      activity seems to be due to enzyme induction, since it was prevented by
      simultaneous administration of cycloheximide or actinomycin D with PFOA. The
      activity of cytosolic long-chain acyl-CoA hydrolase was increased in a dose
      dependent manner by the administration of three peroxisome proliferators with
      diverse chemical structures: alpha-(p-chlorophenoxy)isobutyric acid (clofibric
      acid), 2,2'-(decamethylenedithio)diethanol (tiadenol) and PFOA. The increased
      activity produced by clofibric acid lasted throughout a 22-week treatment. A good
      correlation was found between the activities of cytosolic long-chain acyl-CoA
      hydrolase and peroxisomal beta-oxidation induced by the administration of the
      peroxisome proliferators. These results indicate that cytosolic long-chain acyl
      CoA hydrolase is a suitable parameter for measuring the response of rat liver to
      challenges by peroxisome proliferators.

PMID- 1346070
TI  - S-nitrosylation of proteins with nitric oxide: synthesis and characterization of
      biologically active compounds.
AB  - Endothelium-derived relaxing factor (EDRF) activity has been attributed to the
      highly labile nitric oxide radical (NO). In view of the fact that the plasma and
      cellular milieux contain reactive species that can rapidly inactivate NO, it has
      been postulated that NO is stabilized by a carrier molecule that preserves its
      biological activity. Reduced thiol species are candidates for this role, reacting
      readily in the presence of NO to yield biologically active S-nitrosothiols that
      are more stable than NO itself. Because sulfhydryl groups in proteins represent
      an abundant source of reduced thiol in biologic systems, we examined the reaction
      of several sulfhydryl-containing proteins of diverse nature and function upon
      exposure to authentic NO and EDRF. We demonstrate that S-nitroso proteins form
      readily under physiologic conditions and possess EDRF-like effects of
      vasodilation and platelet inhibition. These observations suggest that S
      nitrosothiol groups in proteins may serve as intermediates in the cellular
      metabolism of NO and raise the possibility of an additional type of cellular
      regulatory mechanism.

PMID- 1346073
TI  - Renal artery stenosis caused by nonspecific arteritis (Takayasu disease): results
      of treatment with percutaneous transluminal angioplasty.
AB  - Renovascular hypertension is common in nonspecific aortoarteritis (Takayasu
      disease). The utility of percutaneous transluminal renal angioplasty in managing
      this disease has been reported infrequently, and technical problems in using this
      treatment method have not been described. We retrospectively evaluated the
      results of renal angioplasty in treating 33 stenoses in 20 patients. Each
      patient's diagnosis was based on the criteria established by the Aortitis
      Syndrome Research Committee of Japan. Criteria for selection of patients for
      angioplasty were (1) severe hypertension uncontrolled by single-drug therapy, (2)
      angiographic evidence of at least 70% stenosis of the renal artery with a
      pressure gradient of more than 20 mm Hg, and (3) a normal sedimentation rate. The
      transfemoral route was used to treat all 33 stenoses. Follow-up examinations
      included blood pressure and medication evaluation 1 day, 1 week, and 4-6 weeks
      after treatment, and thereafter at 6-month intervals. Technical success was
      obtained in 28 lesions (85%) in 17 patients (85%). All failures occurred in the
      presence of coexistent abdominal aortic disease and tight, proximal stenosis of
      the renal artery. Technical difficulties were attributed to the tough,
      noncompliant nature of the stenoses, which were difficult to cross and resisted
      repeated, prolonged balloon inflations. These patients experienced backache and a
      fall in systemic blood pressure during balloon inflation. In one patient, the
      ipsilateral renal vein was injured during angioplasty and required surgery.
      Clinical success was obtained in 14 (82%) of the 17 patients in whom technical
      success was achieved and included cure in six patients and improvement in eight
      others. Follow-up 1-18 months (mean, 8 months) after treatment showed restenosis
      in six (21%) of 28 lesions. We conclude that renal angioplasty in nonspecific
      arteritis is associated with technical difficulties; however, the short-term
      results are good and the complication rate is acceptable.

PMID- 1346074
TI  - A combination of electrocardiographic methods represents a further step toward
      the noninvasive identification of patients with syndrome X.
AB  - Identification of patients with angina but normal coronary arteriograms (syndrome
      X) using noninvasive means would be desirable. The ability of four established
      exercise electrocardiographic methods to identify angina patients with and
      without coronary artery disease was compared with that of a method based on a
      combination of the above (combined method). A treadmill score, a multivariate
      method, the ST segment recovery loop, the ST/heart rate adjustment, and the
      combined method were applied to 112 patients who had typical exertional angina
      and positive exercise tests (greater than 1 mm ST segment depression); 90 had
      documented coronary artery disease and 22 had syndrome X. The combined method and
      the treadmill score had a significantly higher diagnostic accuracy (both 81%, as
      91 of the 112 patients were correctly identified by both methods) than the
      multivariate (66%) and ST segment recovery loop (64%) methods (p less than 0.05).
      The ST/heart rate adjustment had a lower sensitivity for syndrome X than any
      other method (1 of 22). Thus methods that involve the assessment of both ST and
      non ST segment variables have greater accuracy in separating syndrome X and
      coronary artery disease patients than methods relying more heavily on ST segment
      changes.

PMID- 1346076
TI  - Identification of novel RFLPs in the vicinity of CpG islands in Xq28: application
      to the analysis of the pattern of X chromosome inactivation.
AB  - Probes for CpG islands were cloned from the distal long arm of the human X
      chromosome; three of them were found to be polymorphic. A HindIII RFLP was
      identified by the probe 2-25 (DXS606), and it was mapped to the Xq27-Xq28
      boundary. Probes 2-19 (DXS605) and 2-55 (DXS707), which identify EcoRI and MspI
      polymorphisms, respectively, have been mapped to the distal part of Xq28, in the
      G6PD-RCP/GCP gene region. Probe 2-19 has been further localized about 16 kb from
      the 3' end of the G6PD gene. The new RFLPs may be useful for the precise mapping
      of the many disease genes localized in this part of the human X chromosome. Probe
      2-19 is highly informative, and it has been studied in greater detail. Using the
      methylation-sensitive rare-cutter enzyme EagI in conjunction with the polymorphic
      EcoRI site, we were able to demonstrate that the RFLP may be used both to study
      randomness of X chromosome inactivation and for carrier detection in X-linked
      syndromes where nonrandom X inactivation occurs. It is conceivable that the
      combined use of 2-19 and of the probes described so far (pSPT-PGK and M27 beta)
      will make analysis of X inactivation feasible in virtually every female.

PMID- 1346075
TI  - Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21.
AB  - We studied the mechanism of ring chromosome 21 (r(21)) formation in 13 patients
      (11 unique r(21)s), consisting of 7 from five families with familial r(21) and 6
      with de novo r(21). The copy number of chromosome 21 sequences in the rings of
      these patients was determined by quantitative dosage analyses for 13 loci on 21q.
      Nine of 11 r(21)s, including the 5 familial r(21)s, showed no evidence for
      duplication of 21q sequences but did show molecular evidence of partial deletion
      of 21q. These data were consistent with the breakage and reunion of short- and
      long-arm regions to form the r(21), resulting in deletion of varying amounts of
      21q22.1 to 21qter. The data from one individual who had a Down syndrome phenotype
      were consistent with asymmetric breakage and reunion of 21q sequences from an
      intermediate isochromosome or Robertsonian translocation chromosome as reported
      by Wong et al. Another patient, who also exhibited Down syndrome, showed evidence
      of a third mechanism of ring formation. The likely initial event was breakage and
      reunion of the short and long arms, resulting in a small r(21), followed by a
      sister-chromatid exchange resulting in a double-sized and symmetrically dicentric
      r(21). The phenotype of patients correlated well with the extent of deletion or
      duplication of chromosome 21 sequences. These data demonstrate three mechanisms
      of r(21) formation and show that the phenotype of r(21) patients varies with the
      extent of chromosome 21 monosomy or trisomy.

PMID- 1346078
TI  - Microdeletions of chromosome 17p13 as a cause of isolated lissencephaly.
AB  - Lissencephaly (agyria-pachygyria) is a brain malformation manifested by a smooth
      cerebral surface, resulting from arrest of neuronal migration at 10-14 wk
      gestation. Type I, or classical, lissencephaly can occur either in association
      with the Miller-Dieker syndrome (MDS) or as an isolated finding, termed "isolated
      lissencephaly sequence" (ILS). About 90% of MDS patients have visible or
      submicroscopic deletions of 17p13.3. We therefore investigated the possibility
      that some ILS patients have smaller deletions in this chromosomal region. Forty
      five ILS patients with gyral abnormalities ranging from complete agyria to mixed
      agyria/pachygyria and complete pachygyria were studied. RFLP analysis with five
      polymorphic loci in 17p13.3 was performed on all patients and their parents.
      Somatic cell hybrids were constructed on three patients, to confirm a deletion or
      to determine the boundaries of a deletion. In-situ hybridization using cosmid
      probes from within a newly defined lissencephaly critical region was performed on
      31 patients as a further method of deletion detection. Six submicroscopic
      deletions were detected (13.3%). Three of the deletions among 45 ILS patients
      were detected by RFLP analysis, 4 deletions in 31 patients were detected by in
      situ hybridization, and one deletion was detected only by somatic cell hybrid
      studies (in situ hybridization was not performed). Overall, in situ hybridization
      proved to be the most rapid and sensitive method of deletion detection. The
      centromeric boundary of these deletions overlapped that of MDS patients, while
      the telomeric boundary for four ILS deletions was proximal to that of MDS and
      narrows the critical region for a lissencephaly locus.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1346077
TI  - Parental origin of factor IX gene mutations, and their distribution in the gene.
AB  - Genomic amplification followed by direct sequencing enabled us to establish the
      causative mutation in 67 unrelated hemophilia B patients of predominantly German
      origin. With the detection of the mutation, extensive pedigree analysis has
      become feasible. We therefore anticipated that determination of the origin of
      mutation could be achieved in a comparatively great number of families. Although
      these investigations often were restricted by the availability of blood samples
      from the maternal grandparents or great-grandparents, we were able to prove a de
      novo mutation in 9 of 20 families with sporadic hemophilia B and in 3 of 20
      families with a history of the disease. This could be achieved with the aid of
      RFLP analysis and, in one case, where the mutation is still unknown, with the aid
      of biochemical and immunological factor IX assays. Since the maternal grandfather
      was decreased in two of these families, the germ line of origin could not be
      determined precisely. In the remaining families, the female and male germ lines
      turned out to be the origin of mutation in six and four cases, respectively, and
      an effect of paternal age on the mutations observed could not be excluded.
      Furthermore, our data indicate that the hemophilia B gene pool is mainly renewed
      by variable mutations.

PMID- 1346079
TI  - Mapping of 262 DNA markers into 24 intervals on human chromosome 11.
AB  - We have extended our mapping effort on human chromosome 11 to encompass a total
      of 262 DNA markers, which have been mapped into 24 intervals on chromosome 11;
      123 of the markers reveal RFLPs. These clones are scattered throughout the
      chromosome, although some clustering occurs in R-positive bands (p15.1, p11.2,
      q13, and q23.3). Fifty-two of the markers were found to contain DNA sequences
      conserved in Chinese hamster, and some of these 52 also cross-hybridized with DNA
      from other mammals and/or chicken. As the length of chromosome 11 is estimated at
      nearly 130 cM, the average distance between RFLP markers is roughly 1 cM. The
      large panel of DNA markers on our map should contribute to investigations of
      hereditary diseases on this chromosome, and it will also provide reagents for
      constructing either fine-scale linkage and physical maps or contig maps of
      cosmids or yeast artificial chromosomes.

PMID- 1346080
TI  - Isolation and mapping of 68 RFLP markers on human chromosome 6.
AB  - We have isolated 68 new RFLP markers on human chromosome 6. Of these, 64 were
      localized on chromosomal bands by the fluorescent in-situ hybridization (FISH)
      method, 25 on the short arm and 39 on the long arm. Their distribution was
      uneven; the markers were localized predominantly in regions of R-positive
      banding. Eleven markers defined VNTR loci. This expanded collection of DNA
      markers will contribute to high-resolution linkage mapping of genes causing
      inherited disorders and will provide useful reagents for isolation of putative
      tumor-suppressor genes on chromosome 6 that appear to be involved in
      malignancies. Furthermore, the new markers will be guideposts for detailed
      linkage and physical maps of this chromosome.

PMID- 1346082
TI  - Treatment of stress response during balanced anesthesia. Comparative effects of
      isoflurane, alfentanil, and trimethaphan.
AB  - Acute hypertensive responses during nitrous oxide-opioid-relaxant anesthesia are
      a common clinical problem. In adult men undergoing radical prostatectomy
      procedures and anesthetized with a standardized technique, we evaluated the
      effectiveness of alfentanil, isoflurane, and trimethaphan in treating acute
      hemodynamic and stress hormone responses to surgical stimulation. Stress hormone
      concentrations were measured 1 min before skin incision, after the onset of an
      acute hypertensive response, and after returning the mean arterial pressure to
      within 10% of the preincision values with one of the three treatment modalities.
      Pretreatment plasma alfentanil concentrations (151 +/- 47 to 156 +/- 47 ng.ml-1)
      and end-tidal nitrous oxide concentrations (66 +/- 2 to 68 +/- 2%) were similar
      in all three groups. Acute hypertensive events were associated with significantly
      increased concentrations of catecholamines and vasopressin (antidiuretic hormone
      [ADH]). Whereas intravenous alfentanil returned all hormone concentrations to
      preincision values, norepinephrine and glucose concentrations were significantly
      increased after adjunctive isoflurane administration. Although trimethaphan
      decreased the norepinephrine concentration, the epinephrine, beta-endorphin,
      cortisol, ADH, and glucose concentrations were significantly increased compared
      to preincision values. However, the persistent elevation in the posttreatment ADH
      concentration in the trimethaphan group was the only significant difference
      between the three groups. Mean (+/- standard deviation) times to awakening (2.8
      +/- 3.3 to 3.8 +/- 4.2 min), extubation (8.1 +/- 4.8 to 10.3 +/- 8.5 min), and
      orientation (19.6 +/- 20.4 to 24.6 +/- 19.1 min) were similar in all three
      groups. Naloxone was required more frequently in patients in the alfentanil (35%)
      and isoflurane (24%) groups than in the trimethaphan group (4%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1346083
TI  - [Positional cloning of genes responsible for hereditary tumors].
AB  - Recently, remarkable progress in molecular biology has enabled isolation of genes
      responsible for hereditary tumors such as retinoblastoma (RB), Wilms' tumor (WT),
      von Recklinghausen neurofibromatosis (NF 1), and familial adenomatous polyposis
      (FAP). Since patients with FAP develop multiple adenomatous polyps in the colon,
      some of which progress to colon cancer, isolation of the FAP gene allows us a
      rare opportunity to study genetic events underlying the well defined
      morphological changes during progression of colorectal tumors. In this report, we
      presented an approach called "positional cloning" which has become a powerful
      tool for identifying genes responsible for hereditary tumors, as well as
      characteristics of some of such genes.

PMID- 1346081
TI  - Patterns of association between genetic variability in apolipoprotein (apo) B,
      apo AI-CIII-AIV, and cholesterol ester transfer protein gene regions and
      quantitative variation in lipid and lipoprotein traits: influence of gender and
      exogenous hormones.
AB  - Patterns of RFLP association were studied, to identify gene regions influencing
      quantitative variation in lipid and lipoprotein traits (coronary artery disease
      [CAD] risk factors or metabolically related traits). Subjects (118 female and 229
      male; age 20-59 years) were selected for health. Multiple RFLPs were used to
      sample variability in regions around genes for apolipoprotein (apo) B
      (restriction enzymes HincII, PvuII, EcoRI, and XbaI), apo AI-CIII-AIV (BamHI,
      XmnI, TaqI, PstI, SstI, and PvuII) and cholesterol ester transfer protein (TaqI).
      Separate analyses were done by gender. The sample was truncated at mean +/- 4 SD,
      to remove extreme outliers. There was no significant gender difference in RFLP
      genotype frequency distribution. After trait-level adjustment to maximize removal
      of concomitant variability, analysis of variance was used to estimate the
      percentage trait phenotypic variance explained by measured variability in the
      gene regions studied. Fewer gene regions were involved in men, with less
      influence on quantitative trait variation than in women, in whom hormone use
      affected association patterns. Gender differences imply that pooling genders or
      adjusting data for gender effects removes genetic information and should be
      avoided. The association patterns show that variability around the candidate
      genes modulates trait levels: the genes are contributors to the genetics of CAD
      risk variables in a healthy sample.

PMID- 1346085
TI  - [An overview of new prognostic factors in lung cancer].
AB  - The knowledge of prognostic factors such as TNM, performance status, and sex is
      essential for predicting patient outcome and optimal trial design and analysis.
      Recent advances in cytogenetics and molecular biology have yielded new prognostic
      factors such as DNA ploidy, oncogenes and oncogene product. New prognostic
      factors can predict patient outcome and should be incorporated for the
      multivariate analysis of prognostic factors. They can provide a guideline for
      selecting special patient population suitable for adjuvant chemotherapy even in
      the early stage of lung cancer.

PMID- 1346084
TI  - [Combination assay of tumor markers in predicting the effectiveness of
      chemotherapy in non-small lung cancer].

PMID- 1346086
TI  - [New prognostic factors in human gastric carcinomas].
AB  - Correlation between the expression of growth factor/receptor systems or the
      alterations of tumor suppressor genes and biological malignancy of gastric cancer
      was described. Overexpression of many growth factors/receptors, such as EGF, TGF
      alpha, EGF receptor and ERBB2, and reduction of type I receptor for TGF beta may
      be linked with new prognostic factors of gastric carcinomas. The expression of
      cripto, a novel gene of EGF family, shows a tendency to correlate with tumor
      staging of well differentiated gastric adenocarcinomas. p53 gene abnormalities
      take place in 60% of gastric carcinomas including early stage carcinoma. Loss of
      heterozygosity on chromosomes 1q, 7p and 7q is frequently observed in advanced
      gastric carcinomas of well differentiated type. Molecules which regulate tumor
      invasion and metastasis such as nm23, tissue inhibitor of metalloproteinase
      (TIMP) and endogenous galactoside-binding lectin may provide for prognostic
      factors of gastric cancer.

PMID- 1346087
TI  - [Expression of c-erbB-2 protein and vessel invasion in colorectal cancer].
AB  - Using sections of formalin-fixed, paraffin-embedded tissues from 64 colorectal
      cancer patients, the expression of c-erbB-2 oncoprotein was studied
      immunohistochemically. Twenty-seven percent of the cases with liver metastasis
      showed positive staining. On the other hand, only 3% of cases without liver
      metastasis were positive. Expression rates of c-erbB-2 protein in liver
      metastasis cases showed no significant difference between primary operation (26%)
      and recurrence (27%). Of all c-erbB-2 positive patients, 90% (9/10) had liver
      metastasis. Secondly, vessel invasions of 45 rectal cancer patients were studied
      using Victoria Blue (VB) elastic staining and endothelial staining by factor VIII
      related antigen and Ulex europaeus agglutinin I (UEA-I) lectin. VB-HE double
      stain was efficacious to detect vascular invasion, but endothelial staining was
      not. There were statistically more vascular invasions in 30 patients with liver
      or lymph node metastases than in those without metastasis. And in cases with
      metastasis, many vascular invasions into the extra-muscular layer were seen. Both
      vascular invasions and c-erbB-2 protein were valuable indicators of possible
      liver metastasis.

PMID- 1346088
TI  - Identification of Hantaan virus-related structures in kidneys of cadavers with
      haemorrhagic fever with renal syndrome.
AB  - The etiologic agent of haemorrhagic fever with renal syndrome (HFRS), Hantaan
      virus, was first isolated in 1976. Since then numerous Hantaan-like viruses have
      been isolated and five serotypes of Hantavirus have been recognized. Serological
      studies indicate that these viruses are globally distributed, with each serotype
      occurring in specific areas. Hantaan virus has been intensively studied
      antigenically, biochemically, and genetically. However there is still a paucity
      of information on the pathogenesis of Hantaan virus in the human host. In this
      paper, we report the detection by thin section immune electron microscopy of the
      occurrence of numerous dense precipitates, typical inclusion bodies, a surface
      antigen layer, as well as Hantaan virion-like structures in the kidneys of
      patients that died during the acute phase of HFRS. These findings may shed some
      light on understanding the pathogenesis of HFRS in target organs most affected by
      the disease, such as the kidneys.

PMID- 1346089
TI  - 5-hydroxytryptamine is a fast excitatory transmitter at 5-HT3 receptors in rat
      amygdala.
AB  - A fast excitatory synaptic potential mediated by 5-hydroxytryptamine (5-HT) was
      recorded in rat lateral amygdala neurons in brain slices. The synaptic potential
      has brief duration (tens of milliseconds), is mimicked by 5-HT, is potentiated by
      a 5-HT uptake inhibitor, and is blocked by selective 5-HT3 receptor antagonists.
      The underlying synaptic current reversed polarity at about 0 mV. This is an
      example of fast neurotransmission in the mammalian brain mediated by an amine
      rather than an amino acid. The antiemetic, anxiolytic, and perhaps antipsychotic
      actions of 5-HT3 antagonists might result from blockade of such synapses.

PMID- 1346090
TI  - Pertussis toxin and voltage dependence distinguish multiple pathways modulating
      calcium channels of rat sympathetic neurons.
AB  - Agonist-induced suppression of current in voltage-gated Ca2+ channels was studied
      in rat sympathetic neurons. We have previously distinguished two intracellular
      signaling pathways used by muscarinic agonists to suppress neuronal Ca2+ current
      one fast and membrane delimited, the other slow and acting via a diffusible
      second messenger. We now show that the fast pathway is sensitive mainly to
      pertussis toxin and shifts the gating of Ca2+ channels to more positive voltages
      (voltage dependent). The slow pathway is pertussis toxin insensitive and
      depresses currents at all test potentials (voltage independent). Muscarinic
      agonists may also activate a pertussis toxin-insensitive fast pathway. alpha
      Adrenergic agonists use the fast pertussis toxin-sensitive and the fast
      insensitive pathways, but not the slow one.

PMID- 1346091
TI  - Probing the active site of the reconstituted aspartate/glutamate carrier from
      bovine heart mitochondria: carbodiimide-catalyzed acylation of a functional
      lysine residue.
AB  - Upon modification of the reconstituted aspartate/glutamate carrier by various
      amino acid-reactive chemicals a functional lysine residue at the exofacial
      binding site was identified. The inactivation of transport function by the lysine
      specific reagents pyridoxal phosphate (PLP, IC50 400 microM) and 4-acetamido-4'
      isothiocyanostilbene-2,2'-disulfonate (SITS, IC50 300 microM) could specifically
      be suppressed by the substrates aspartate and glutamate; a 50% substrate
      protection was observed at half-saturation of the external binding site. The same
      held true for 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC, IC50 500
      microM) and diethyl pyrocarbonate (DEPC, IC50 20 microM), two reagents known to
      modify carboxylic or histidinyl side-chains, respectively. EDC, however, turned
      out to catalyze an acylation of the active site lysine by activating carboxyls
      that had to be present in the incubation medium. This special mechanism, which
      was proven by protein labelling using EDC/[14C]succinate, necessitates a lysine
      side-chain of high reactivity and low pK, since the modification had to occur at
      pH less than or equal to 6.5, i.e. not too far from the pK of the carboxyl to be
      activated. All reagents applied, additionally including 4,4'
      diisothiocyanostilbene-2,2'-disulfonate (DIDS, IC50 10 microM), were effective at
      this pH. Competition experiments revealed interaction of EDC, PLP, SITS and
      probably DIDS at the same active site lysine. For DEPC a lysine modification
      could not be ruled out. Yet, a model comprising a histidine juxtaposed to the
      lysine seems to be appropriate.

PMID- 1346092
TI  - Comparison of the conversion rates of alpha-linolenic acid (18:3(n - 3)) and
      stearidonic acid (18:4(n - 3)) to longer polyunsaturated fatty acids in rats.
AB  - The delta 6-desaturase reaction is regarded to be the rate-limiting step in the
      conversion of linoleic acid (18:2(n - 6)) to arachidonic acid (20:4(n - 6)). The
      same is probably also the case with the conversion of alpha-linolenic acid
      (18:3(n - 3)) to eicosapentaenoic acid (20:5(n - 3)). However, there are very few
      in vivo studies that directly compared the conversion rate between 18:3(n - 3)
      and stearidonic acid (18:4(n - 3)), which is the delta 6-desaturated product of
      18:3(n - 3). We compared this rate by feeding rats on a lipid-free diet
      supplemented with lard (9%, w/w) and 18:3(n - 3) ethyl ester (1%) diet or on a
      diet containing lard (9%) and 18:4(n - 3) ethyl ester (1%). A lard (10%)
      supplemented diet was used as the control diet. The fatty acid compositions of
      total phospholipids, triglycerides and free fatty acids of both liver and plasma
      were measured after 1 or 3 weeks on different diets. The molar ratio of 20:5(n -
      3) of most lipid fractions was about 2-fold higher in rats fed the 18:4(n - 3)
      supplemented diet than in rats fed the 18:3(n - 3)-supplemented diet. 18:4(n - 3)
      was found in the liver lipid fraction in only a very small amount, even in the
      18:4(n - 3)-supplemented groups. Thus, desaturation at C-6 is suggested to be the
      rate-limiting step in the conversion of 18:3(n - 3) to 20:5(n - 3).

PMID- 1346094
TI  - Multidrug resistance (MDR 1) in leukemia: is it time to test?

PMID- 1346093
TI  - Induction by psychotropic drugs and local anesthetics of DnaK and GroEL proteins
      in Escherichia coli.
AB  - We examined effects of psychotropic drugs and local anesthetics on the synthesis
      of heat shock proteins in Escherichia coli. Chlorpromazine, a phenothiazine
      derivative, was shown to induce DnaK and GroEL proteins, major heat shock
      proteins in E. coli. The inductions of these proteins were not observed in an
      rpoH (= htpR) amber mutant strain, indicating that the heat shock sigma factor
      sigma 32 was required for their inductions. Northern blot hybridization analysis
      revealed that chlorpromazine induced increases of messenger RNAs for the DnaK and
      GroEL proteins. Thus, the induction occurred at the level of transcription.
      Chlorpromazine also induced non-heat shock proteins with molecular masses of 21
      kDa, 20 kDa, and 17 kDa, even in the rpoH mutant strain. Other psychotropic drugs
      and local anesthetics, namely, dibucaine, lidocaine, imipramine, tetracaine and
      procaine, also induced DnaK and GroEL proteins and the small molecular weight
      proteins.

PMID- 1346095
TI  - Lipoprotein-associated coagulation inhibitor (LACI) is a cofactor for heparin:
      synergistic anticoagulant action between LACI and sulfated polysaccharides.
AB  - Lipoprotein-associated coagulation inhibitor (LACI) is a plasma-derived protein
      that inhibits tissue factor (TF)/factor VIIa-induced coagulation in a factor Xa
      dependent manner. The roles of endogenous plasma LACI and exogenously added LACI
      and heparin, in the regulation of coagulation, initiated via the intrinsic and
      extrinsic pathways, were studied using the activated partial thromboplastin time
      (APTT) and the modified prothrombin time (PT) assays, respectively. Both LACI
      depleted plasma and normal plasma have identical APTTs and similar prolongations
      of the APTT in response to heparin; both are fully anticoagulated (arbitrarily
      defined as clotting times of greater than 1 hour) at similar concentrations of
      heparin. These results indicate that heparin is an effective anticoagulant when
      coagulation is initiated by the intrinsic pathway and that endogenous LACI is not
      significantly involved in the regulation of this pathway. The PT of normal plasma
      is only marginally longer than that of LACI-depleted plasma in the absence of
      heparin, suggesting that endogenous plasma LACI has a very limited capacity to
      inhibit TF-induced clotting. However, in the presence of heparin, the PTs of LACI
      depleted plasma and normal plasma are different. Prolongation of the PT occurred
      only moderately and linearly with increasing concentrations of heparin in LACI
      depleted plasma. In contrast, normal plasma showed a greater extent of PT
      prolongation in response to heparin and the plasma became fully anticoagulated at
      a certain threshold concentration of heparin. These results suggest that LACI
      serves as a cofactor for heparin and thus greatly enhances the inhibition of TF
      induced coagulation. LACI-depleted plasma was supplemented with purified
      recombinant LACI and/or heparin and the effects on TF-induced clotting were
      studied. A combination of LACI and heparin greatly enhanced anticoagulation
      compared with LACI or heparin alone. Many sulfated polysaccharides were also
      found to enhance the LACI-dependent inhibition of TF-induced clotting. By weight,
      the relative potencies of these compounds are: low molecular weight heparin (mean
      Mr, 5,100) greater than unfractionated heparin greater than low molecular weight
      heparin (mean Mr, 3,700) greater than pentosan polysulfate greater than dermatan
      sulfate greater than dextran sulfate greater than heparan sulfate. Based on the
      above results, it is concluded that LACI is a cofactor for heparin in the
      inhibition of TF-induced clotting and that LACI and sulfated polysaccharides act
      synergistically in whole plasma.

PMID- 1346096
TI  - Pneumocystis carinii infection complicating cytotoxic therapy in two patients
      with lymphopenia, but a normal total white cell count.

PMID- 1346097
TI  - Treatment of advanced pancreatic carcinoma with the somatostatin analogue BIM
      23014. Preliminary results of a pilot study.
AB  - Treatment of advanced pancreatic cancer has not improved substantially in recent
      years. The search for new agents or new therapeutic modalities may be critical
      for further development in the therapy of this disease. Experimental and clinical
      findings suggest that it might be possible to develop a new hormonal therapy for
      exocrine cancer of the pancreas based on new somatostatin analogues. Preliminary
      results indicate clinical activity and increased survival in some patients. In
      this study, 19 patients with advanced exocrine pancreatic carcinoma were given
      the somatostatin analogue BIM 23014 using a range of doses from 250
      micrograms/day to 1 mg/day. One patient had a partial response, 6 patients had
      stable disease, and 11 had progressive disease. Six patients showed a sharp
      improvement in pain and performance status. Side effects were mild. Plasma levels
      of growth hormone were evaluated in ten patients and remained unchanged. The
      clinical activity observed, even if limited, warrants further investigation using
      more appropriate schedules and administration techniques.

PMID- 1346098
TI  - Gestational and nongestational trophoblastic tumors distinguished by DNA
      analysis.
AB  - In three patients in whom a diagnosis of gestational trophoblastic tumor was
      possible on the basis of pathology and elevated levels of serum human chorionic
      gonadotrophin, locus-specific minisatellite probes were used to identify
      restriction fragment length polymorphisms (RFLP) in DNA from the tumor, the
      patient, and her partner. On the basis of results from these studies, one tumor,
      originally diagnosed as a germ cell tumor, was reclassified as a gestational
      choriocarcinoma, whereas a second tumor, diagnosed as gestational
      choriocarcinoma, was shown to be of nongestational origin. In the third case, a
      diagnosis of gestational trophoblastic tumor was confirmed, but in this case the
      androgenetic origin of the tumor indicated that it was derived, not from the
      antecedent term pregnancy, but from a previous pregnancy with hydatidiform mole.
      This study clearly demonstrates the value of DNA analysis in the classification
      of tumors with trophoblastic differentiation.

PMID- 1346099
TI  - Aberrant expression of the c-erbB-2/neu protooncogene in ovarian cancer.
AB  - Overexpression of the c-erbB-2/neu protooncogene has recently been shown in
      ovarian tumors collected from the United States. It is known that environmental
      and cultural factors may contribute to certain types of cancer, therefore, we
      examined expression of c-erbB-2/neu in ovarian tumors collected from China by
      immunohistochemical staining. Out of 81 tumor specimens, 57 (70.4%) were found to
      be immunopositive, whereas only one out of 17 (5.9%) normal ovarian tissue
      samples was slightly positive. Our results indicate that overexpression of c-erbB
      2/neu is a general phenomenon for ovarian cancer regardless of different
      population. To search for a c-erbB/neu overexpressing cell line for future study
      on molecular mechanism, we also analyzed 13 cancer cell lines from the female
      genital tract for expression of c-erbB-2/neu. The c-erbB-2/neu RNA was found to
      be overexpressed at least 100-fold in one of the four ovarian cancer cell lines
      examined. An aberrant c-erbB-2/neu RNA was also found to be overexpressed in this
      cell line. Southern blot analysis indicated that the c-erbB-2/neu was amplified 2
      4-fold in this line, and some of these alleles have structural alteration which
      may account for expression of the aberrant c-erbB-2/neu RNA. Since the 2-4-fold
      gene amplification is not proportional to the greater than 100-fold
      overexpression in RNA, other mechanisms such as transcriptional or
      posttranscriptional control must be involved in overexpression of this gene in
      ovarian cancer.

PMID- 1346100
TI  - TNF-alpha production by U937 promonocytes is enhanced by factors released from
      HIV-infected T4 lymphocytes: TNF-alpha is one of the mediators causing lysis of
      HIV-infected T4 cells.
AB  - In the present study, we have shown that the addition of culture supernatants
      from HIV-infected SupT1 cells (T4) but not from noninfected cells markedly
      increased the production of TNF-alpha by U937 promonocytic cells after
      stimulation with phorbol 12-myristate 13-acetate (PMA). Pretreatment of
      supernatants with the antibodies to granulocyte/macrophage colony-stimulating
      factor (GM-CSF) or TNF-alpha, but not interferon-gamma, significantly diminished
      this enhancing effect. These results suggest that HIV may play an indirect role
      by producing cytokines from infected T4 cells that can lead to an increased
      production of TNF-alpha by monocytic cells. Further, TNF-alpha produced by U937
      cells following stimulation with PMA plus lipopolysaccharide or with
      phytohemagglutinin induced lysis of HIV-infected T cells. TNF-alpha-induced
      cytotoxicity was markedly higher toward HIV-infected than toward noninfected T4
      cells. Addition of antibody to TNF-alpha during the cytotoxic phase of response
      resulted in a reduction of about 50% in the percentage of cytotoxicity,
      indicating TNF-alpha as one of the lytic mediators.

PMID- 1346101
TI  - Beta-adrenergic agonists in asthma.

PMID- 1346102
TI  - [Therapy of coronary disease].

PMID- 1346103
TI  - [Imidazole receptors: site of action of a new generation of antihypertensive
      drugs. Current status and future prospects].

PMID- 1346104
TI  - Baculovirus-mediated expression and characterisation of rat glycogen synthase
      kinase-3 beta, the mammalian homologue of the Drosophila melanogaster zeste-white
      3sgg homeotic gene product.
AB  - Molecular cloning of glycogen synthase kinase-3 (GSK-3) has demonstrated the
      existence of a novel form, termed GSK-3 beta, which is highly related to the well
      characterised GSK-3 alpha protein but derived from a distinct gene. The cDNA
      cloning also revealed a striking degree of amino acid identity between the two
      GSK-3 proteins, particularly the beta-form, and the zeste-white3/shaggy (zw3sgg)
      homeotic gene of Drosophila melanogaster. Abrogation of zw3sgg causes pleiotropic
      effects on fruitfly development affecting segmental organisation and cell fate
      determination. In view of the potential importance of GSK-3 beta in mammalian
      development and the lack of previous characterisation, we have expressed this
      protein in insect cells using recombinant baculovirus. A rapid purification
      scheme has been developed yielding essentially pure GSK-3 beta protein in three
      chromatographic steps. The protein has autonomous protein kinase activity and
      similar, but not identical, substrate preferences to GSK-3 alpha. Both GSK-3
      proteins activate the MgATP-dependent form of protein phosphatase-1 and thus
      display 'factor A' activity. Since GSK-3 beta exhibits an identical site
      specificity to GSK-3 alpha with respect to phosphorylation of the proto
      oncogene/transcription factors c-jun and c-myc, it is likely that the Drosophila
      zw3sgg protein kinase has a similar specificity for such transcription factors
      which may underlie the pleiotropic phenotypes observed when the Drosophila
      homologue is mutationally inactivated.

PMID- 1346105
TI  - Memory in helper T cells of minor histocompatibility antigens, revealed in vivo
      by alloimmunizations in combination with Thy-1 antigen.
AB  - A cooperative antibody response in which T helper (Th) cells recognize minor
      histocompatibility antigens (mha) and B cells recognize Thy-1 antigen, is used to
      explore memory in the T cell compartment. In contrast to B cell memory, Th memory
      reaches a plateau rapidly, although Th memory of Thy-1 itself (or an associated
      antigen) behaves exceptionally in this respect. The plateau then extends over
      several weeks at least. Single mha, among them H-Y, generate detectable memory.
      Incompatible H-2 antigens, including class I antigens on their own, inhibit this
      response through what appears to be a mechanism of intracellular antigenic
      competition. Antigen presentation in this system is by host cells, as judged by
      lack of donor-specific restriction. Memory resides in both the CD45RA+ and CD45RA
      compartments, although the majority of memory Th cells have the latter
      phenotype.

PMID- 1346106
TI  - Latent help to and from H-2 antigens.
AB  - An optimized system for probing allo-immunity to major histocompatibility complex
      (MHC) antigens by means of adoptive transfer is used to confirm and extend
      previous work showing that naturally occurring class I MHC antigens, while
      capable of inducing Th activity when presented in combination with other allo
      antigens, fail to do so on their own. The Th activity which they do induce
      develops slowly, after repeated immunizations, and can properly be described as
      "latent". Latency, or "cripticity" as it is also termed, may help explain how
      autoimmune disease is initiated.

PMID- 1346107
TI  - Restricted V alpha 2.3 gene usage by CD4+ T lymphocytes in bronchoalveolar lavage
      fluid from sarcoidosis patients correlates with HLA-DR3.
AB  - The alpha/beta T cell receptor (TcR) V gene usage of bronchoalveolar lavage (BAL)
      lymphocytes and peripheral blood lymphocytes (PBL) from 11 sarcoidosis patients
      and 4 healthy controls was investigated, using eight alpha/beta TcR V gene
      product-specific monoclonal antibodies (mAb). Twenty-seven percent (3/11) of the
      sarcoidosis patients had a highly significant increase in V alpha 2.3+CD4+ T
      lymphocytes in the bronchoalveolar space, while displaying normal frequencies of
      these T cells in peripheral blood. The reactivities with the remaining seven TcR
      mAb were normal. In the control group, no compartmentalization of any T cells was
      seen. Four of the patients expressed the HLA-DR3 (w17), DQw2 haplotype.
      Interestingly, the three patients with distinct signs of compartmentalized V
      alpha 2.3+CD4+ T cells all expressed this HLA haplotype. Additionally, a fourth
      patient with pronounced, although less significant, accumulation of V alpha
      2.3+CD4+ T cells in the lung, was also HLA-DR3(w17), DQw2+. Expression of V alpha
      2.3+CD4+ T cells in BAL of these patients correlated with clinical disease, as
      revealed on re-analyzing the four patients after 6 months or longer. Predominant
      TcR V alpha 2.3 gene usage in compartmentalized CD4+ BAL T lymphocytes, linked to
      HLA-DR3(w17), DQw2 haplotype, may thus indicate presence of a specific antigen
      localized to the lungs of sarcoidosis patients.

PMID- 1346108
TI  - Intestinal intraepithelial lymphocyte T cells are resistant to lpr gene-induced T
      cell abnormalities.
AB  - The mucosal immune system of the gastrointestinal (GI) tract consists of Peyer's
      patches (PP), which are IgA inductive sites, and more diffuse effector regions
      which include cells in the intraepithelial lymphocyte (IEL) compartment. Since
      autoimmune MRL lpr/lpr (MRL/lpr) mice develop a proliferating CD3+, CD4-, CD8-
      (double negative; DN), B220+ T cell subset in systemic lymphoid tissue, we have
      initiated studies to determine the distribution of CD3+, DN, B220+ T cells (B220+
      T cells or lpr/lpr T cells) in the GI immune system. Specifically, we examined T
      cell subsets separated according to expression of CD4, CD8, Thy-1, B220,
      alpha/beta T cell receptor (TcR) and gamma/delta TcR in PP and IEL of MRL/lpr
      mice at 6, 12 and 21 weeks of age. Increased numbers of CD3+ T cells were noted
      in both PP and spleen of 12- and 21-week-old mice in which the development of
      autoimmune disorders were also evident. However, normal numbers of CD3+ IEL T
      cells were seen in MRL/lpr mice in all three age groups tested. When the presence
      of T cell lymphadenopathy was examined in both IgA inductive and effector
      tissues, the PP followed the B220+ T cell pattern seen in the spleen, where
      approximately 30%-50% of CD3+ T cells in the PP of 12- and 21-week-old MRL/lpr
      mice expressed the phenotype of lpr/lpr T cells and greater than 90% were
      alpha/beta TcR+. On the other hand, B220+ T cells had not developed in PP or
      spleen of 6-week-old MRL/lpr mice. Of interest was the finding that IEL from
      lpr/lpr homozygous mice did not contain B220+ T cells in any age group tested. In
      this regard, the IEL of MRL/lpr mice comprised an identical pattern and frequency
      of CD4-/CD8+, CD4+/CD8-, DN and CD4+/CD8+ (double positive, DP) T cell subsets as
      their normal counterparts (i.e. MRL +/+, BALB/c and C3H/HeN mice) which consisted
      of approximately 75%, approximately 7.5%, approximately 7.5% and approximately
      10%, respectively. Further, Thy-1, gamma/delta TcR and alpha/beta TcR expression
      in these four subsets of MRL/lpr IEL were very similar to normal mice. These
      results suggest that the intestinal IEL compartment is minimally affected by the
      lpr/lpr mutation which induces T cell abnormalities and indicate that B220+ T
      cells do not preferentially home to IEL. Further, our results support the concept
      that IEL T cells develop as a separate T cell lineage from thymus-derived cells.

PMID- 1346110
TI  - Augmentation of major histocompatibility complex class I and ICAM-1 expression on
      glial cells following measles virus infection: evidence for the role of type-1
      interferon.
AB  - An intracellular staining procedure for the cytoskeletal marker, glial fibrillary
      acidic protein of astrocytes, has been developed which allows flow cytometric
      phenotyping of astrocytes within complex mixtures of glial cells. Employing this
      technique, we show here that measles virus infection of rat mixed glial cell
      cultures results in a rapid augmentation of major histocompatibility complex
      (MHC) class I and ICAM-1 on the majority of astrocytes in culture. MHC class I
      levels are increased on macrophages/microglia but ICAM-1 expression is not
      normally affected on this cell type. Some MHC class II induction is also observed
      after virus infection but only on astrocytes. A type-I interferon (IFN)-inducible
      protein, Mx, was identified in cultured glial cells after infection.
      Qualitatively comparable MHC class I and ICAM-1 enhancement after addition of
      type-I IFN, supports the conclusion that this cytokine(s) released as a result of
      virus infection, is responsible for alterations in the expression of molecules on
      glial cells, that are involved in T cell recognition. Astrocytes after viral
      infection were more susceptible to alloantigen-specific cytotoxic T lymphocytes
      and cytotoxic T lymphocyte activity was substantially reduced in the presence of
      mAb specific for MHC class I, ICAM-1 and LFA-1 but not MHC class II. The
      relevance of these findings to T cell recognition of virus-infected cells in the
      central nervous system is discussed.

PMID- 1346109
TI  - Internalization of glycosyl-phosphatidylinositol (GPI)-anchored lymphocyte
      proteins. II. GPI-anchored and transmembrane molecules internalize through
      distinct pathways.
AB  - Ly-6A.2 (T cell-activating protein, TAP) and Thy-1 are glycosyl-phosphatidyl
      inositol (GPI)-anchored proteins expressed on the surface of murine T
      lymphocytes. We have found that Ly-6A.2 (TAP) and Thy-1 are internalized by T
      cells. In the present study we have investigated whether these GPI-anchored
      proteins enter cells by endocytosis through coated pits. Two lines of evidence
      argue against the involvement of coated pits in the internalization of Ly-6A.2
      (TAP) and Thy-1. First, drugs that effectively blocked the endocytosis of
      transferrin receptor and H-2 class I molecules, (which are known to be
      internalized via coated pits) did not inhibit the internalization of the GPI
      anchored proteins. Second, in ultrastructural analyses, Ly-6A2 (TAP) and Thy-1,
      in contrast to the transferrin receptor, were rarely found in coated pits or
      vesicles. These observations suggest that the GPI-anchored proteins on T
      lymphocytes are internalized by a distinct pathway that does not involve
      endocytosis through coated pits.

PMID- 1346111
TI  - ICAM-1-independent lymphocyte transmigration across high endothelium:
      differential up-regulation by interferon gamma, tumor necrosis factor-alpha and
      interleukin 1 beta.
AB  - The adhesion of lymphocytes to cytokine-treated high endothelium was studied
      using cultured high endothelial cells (HEC). Pretreatment of the HEC layer with a
      variety of cytokines caused up-regulation of lymphocyte adhesion with the effects
      ordered interferon gamma (IFN-gamma) greater than tumor necrosis factor-alpha
      (TNF-alpha) greater than or equal to interleukin 1 beta (IL 1 beta). Increased
      lymphocyte adhesion was found to be independent of ICAM-1 as expression by HEC
      was not increased by cytokines and antibodies against ICAM-1 did not block
      adhesion. The peptide CS1 and anti-beta 1 integrin subunit antibodies, however,
      caused partial inhibition of lymphocyte adhesion thus indicating a role for
      fibronectin on HEC and alpha 4 beta 1 on lymphocytes. Study of the kinetics of
      lymphocyte adhesion showed that the effects of IFN-gamma and TNF-alpha were
      persistent and remained detectable 2.5 h after removal of the cytokines whereas
      the effects of IL 1 beta were transient and were not sustained beyond 1 h. All of
      the cytokines used caused transient increases in the number of surface-bound
      lymphocytes with IFN-gamma greater than TNF-alpha greater than or equal to IL 1
      beta, however, the most dramatic effect was on the transmigration of lymphocytes
      across the HEC. Both IFN-gamma and TNF-alpha caused sustained increased
      transmigration with IFN-gamma having the greater effect. IL 1 beta had little
      effect on transmigration. This model demonstrates that the binding and
      transmigration of lymphocytes across HEC can be differentially regulated by the
      actions of individual cytokines. These results support the concept that locally
      produced cytokines regulate HEC function within the lymph node.

PMID- 1346112
TI  - The genetics of IgG4 deficiency: role of the immunoglobulin heavy chain constant
      region and HLA loci.
AB  - IgG4 deficiency is very common (1/400 in the Italian population) and provides a
      good model for analyzing the genetic factors involved in Ig subclass
      deficiencies. We have previously reported an association between some
      immunoglobulin heavy chain constant region (IGHC) polymorphisms and the IgG4
      deficiency. The associated polymorphisms spanned the region between the GP and
      the G4 genes. A larger sample composed of 50 healthy blood donors with IgG4
      deficiency (less than 0.001 g/l IgG4), not carrying homozygous gene deletions,
      together with 82 first-degree relatives is now examined. The results confirmed
      the association of the deficiency with IGHC polymorphisms, and detected a new
      association with the HLA-D locus with a strong additive effect between the two
      systems. However, despite these associations and a highly significant risk for
      IgG4 deficiency within families, close linkage with either IGHC or HLA loci was
      not apparent by the affected sib pair method. These findings suggest that several
      concomitant, possibly cooperating, genetic factors may be involved in IgG4
      deficiency.

PMID- 1346113
TI  - CD4+ T cell-mediated killing of major histocompatibility complex class II
      positive antigen-presenting cells (APC). III. CD4+ cytotoxic T cells induce
      apoptosis of APC.
AB  - A subset of CD4+ T cells, belonging to the T helper type 1 (Th1) cells, kills
      antigen-presenting cells (APC) in an antigen-specific and major
      histocompatibility (MHC) class II-restricted way. Evidence is presented that CD4+
      cytotoxic T lymphocytes (CTL) induce apoptosis or programmed cell death within
      susceptible APC as witnessed by quantitative DNA fragmentation. Apoptosis is more
      reliable to determine cell death than the 51Cr-release assay, because some cells
      demonstrate resistance to CD4-mediated lysis in the 51Cr-release assay. Apoptosis
      becomes manifest after 2 to 4 h of incubation preceding the disintegration of the
      target cells which is detectable between 12 and 24 h as measured by the 51Cr
      release assay. Unstimulated B cells, which are not killed, but function as APC,
      do not undergo apoptosis, whereas lipopolysaccharide or anti-mu-activated B cell
      blasts show apoptosis and are efficiently lysed. Several CD4+ Th2-type cells
      tested, which did not demonstrate killing of APC as measured by the 51Cr-release
      assay, are unable to mediate programmed cell death of appropriate APC.
      Actinomycin D or cycloheximide, inhibitors of transcription and translation,
      respectively, fail to prevent apoptosis of APC excluding the involvement of newly
      synthesized soluble products as mediators of killing. Pretreatment of CD4+ CTL,
      but not of APC with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, a
      specific inhibitor of the anion transport, efficiently prevents apoptosis of APC,
      although the secretion of interleukins is not affected. We propose, that upon
      contact of the CD4+ CTL with APC, molecules of yet undefined nature are activated
      and released in a polar fashion at the contact site and induce the endogenous
      pathway of programmed cell death.

PMID- 1346114
TI  - Regulation of D-3 phosphoinositides during T cell activation via the T cell
      antigen receptor/CD3 complex and CD2 antigens.
AB  - An immediate consequence of T cell activation via the T cell receptor (TcR)/CD3
      complex and CD2 antigen is the hydrolysis of phosphatidylinositol-(4,5)
      bisphosphate and the generation of inositol-(1,4,5)-trisphosphate and
      diacylglycerol which then regulate intracellular calcium and protein kinase C.
      Changes in cellular levels of phosphoinositides phosphorylated on the D-4 and D-5
      position during T cell activation have been well documented. Recently it has been
      proposed that phosphoinositides phosphorylated on the D-3 position of the
      inositol ring by a novel phosphoinositide (PI) 3 kinase may also be important in
      cell activation. In the present study we have examined the levels and regulation
      of D-3 phosphoinositides in T cells activated by the TcR/CD3 complex and CD2
      antigens. The data show the existence of phosphatidylinositol-(3)-monophosphate
      [PtdIns(3)P], phosphatidylinositol-(3,4)-bisphosphate [PtdIns(3,4)P2] and
      phosphatidylinositol-(3,4,5)-trisphosphate [PtdIns(3,4,5)P3] in T cells.
      Activation of the TcR/CD3 complex or CD2 antigen results in modulation of
      PtdIns(3,4)P2 and a putative PtdIns(3,4,5)P3 in T cells but does not change
      levels of PtdIns(3)P. These data provide the first evidence that lipid products
      of a PI3 kinase exist in T cells.

PMID- 1346116
TI  - Microtubule-associated protein autophosphorylation alters in vitro microtubule
      dynamic instability.
AB  - While phosphorylation of high-molecular-weight microtubule-associated proteins
      (MAPs) alters the assembly properties of microtubules in vitro, virtually nothing
      is known about the influence of MAP phosphorylation on the time-scale of
      microtubule polymer length redistribution. The latter has been used as an index
      of microtubule assembly/disassembly turnover as predicted by the dynamic
      instability model (Mitchison, T.M. and Kirschner, M.W. (1984) Nature 312, 237
      242). We have now determined that under conditions leading to the incorporation
      of 8-10 mol phosphoryl groups per mol MAP-2 (and about 0.2 mol phosphoryl groups
      per mol MAP-1 and tau), we can reproducibly observe significant acceleration in
      the polymer length redistribution process in a manner consistent with greater
      microtubule dynamic instability. We have also found that MAP phosphorylation
      resulted in more extensive release of MAPs from microtubules as a function of
      increasing salt concentration. These results are consistent with a weakening of
      MAP-microtubule interactions upon phosphorylation.

PMID- 1346115
TI  - Differential effect of interleukin 1 on naive and memory CD4+ T cells.
AB  - Freshly derived murine CD4+ T cells are divided into naive and memory cells based
      on the expression of CD45 isoforms. Cross-linking the T cell receptor CD3 complex
      either by plastic-bound anti-CD3 antibodies or the antibody presented on non
      lymphoid Fc gamma receptor type II-positive Chinese hamster ovary cells in
      absence of competent antigen-presenting cells fails to activate naive cells to
      either secrete cytokines or to proliferate. In contrast, memory cells secrete
      their characteristic cytokines [interleukin (IL) 2, IL4, and interferon-gamma]
      and show significant proliferation to this stimulus. IL 1 however, is required
      for their optimal clonal expansion. Differential expression of IL 1 receptor mRNA
      in memory cells also correlate with their responsiveness to IL 1. Thus, these
      data reveal a basic difference in the requirements for activation of naive and
      memory CD4+ T cells.

PMID- 1346118
TI  - Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors.
AB  - Previous experiments in our laboratory suggested that ammonium toxicity could be
      mediated by the NMDA type of glutamate receptors. To assess this hypothesis we
      tested if MK-801, a specific antagonist of the NMDA receptor, is able to prevent
      ammonium toxicity. Mice and rats were injected i.p. with 12 and 7 mmol/kg of
      ammonium acetate, respectively. 73% of the mice and 70% of the rats died.
      However, when the animals were injected i.p. with 2 mg/kg of MK-801, 15 min
      before ammonium injection, only 5% of the mice and 15% of the rats died. The
      remarkable protection afforded by MK-801 indicates that ammonia toxicity is
      mediated by the NMDA receptor.

PMID- 1346117
TI  - Functional relationships between cyclodextrin glucanotransferase from an
      alkalophilic Bacillus and alpha-amylases. Site-directed mutagenesis of the
      conserved two Asp and one Glu residues.
AB  - Comparison of the amino acid sequences of cyclodextrin glucanotransferases
      (CGTases) with those of alpha-amylases revealed that two Asp and one Glu
      residues, which are considered to be the catalytic residues in alpha-amylases,
      were also conserved in CGTases. To analyze the function of the three conserved
      amino acid residues in CGTases, site-directed mutagenesis was carried out. The
      three mutant CGTases, in which Asp229, Glu257 and Asp328 were individually
      replaced by Asn or Gln, completely lost both their starch-degrading and beta
      cyclodextrin-forming activities, whereas another mutant CGTase, in which Glu264
      was replaced by Gln, retained these activities. The three inactive enzymes
      retained the ability to be bound to starch. These results suggest that Asp229,
      Glu257 and Asp328 play an important role in the enzymatic reaction catalyzed by
      CGTase and that a similar catalytic mechanism is present in both CGTases and
      alpha-amylases.

PMID- 1346119
TI  - International workshop on intermediate uveitis, Gutersloh, July 5-6, 1990.

PMID- 1346120
TI  - Dual Bar homeo box genes of Drosophila required in two photoreceptor cells, R1
      and R6, and primary pigment cells for normal eye development.
AB  - In the Bar mutation of Drosophila, ommatidial differentiation is known to be
      suppressed in the anterior portion of the eye. Our structural analysis shows that
      the Bar region contains a pair of homeo box genes, BarH1 and BarH2. These genes
      encode polypeptides similar in size and sequence and share a common homeo domain
      that is identical in sequence except for putative trans-activator-binding sites.
      We also show, by mosaic analysis and immunostaining with anti-BarH1/BarH2
      antibodies, that BarH1 and BarH2 are not only specifically coexpressed but also
      functionally required in R1/R6 prephotoreceptors and primary pigment cells in
      developing ommatidia. In R1/R6, the expression of BarH1 and BarH2 appears to be
      regulated by rough and glass gene products. BarH1 and BarH2 proteins are
      essential to normal lens formation, formation of three types of pigment cells,
      and elimination of excess cells from mature ommatidia. Taken together, our
      results suggest that Bar homeo domain proteins may play key roles in the fate
      determination processes of pigment cells and cone cells.

PMID- 1346121
TI  - Effectiveness of advice to reduce alcohol consumption in hypertensive patients.
AB  - The relation between alcohol consumption and blood pressure is well recognized,
      and advice to reduce alcohol plays an important part in the management of
      hypertensive patients. We have evaluated the effectiveness of this advice in a
      randomized, controlled, single-blind clinical study. After a 2-week run-in
      period, hypertensive men regularly consuming more than 20 units/wk (1 unit = 10
      g) of alcohol were randomly assigned either to the "advice" or control group and
      were seen at 2-week intervals over an 8-week study period. The outcome measures
      were: reported alcohol consumption (1-week retrospective diary), markers of
      alcohol consumption (serum gamma-glutamyl transpeptidase, aspartate
      aminotransferase, uric acid, mean corpuscular volume), and blood pressure
      (sitting and standing). Over 18 months, 67 men who drank more than 20 units/wk of
      alcohol were seen. Twenty-six either were excluded, refused to participate, or
      dropped out due to nonattendance. Forty-one patients completed the study. After
      intervention, reported alcohol consumption fell from 60 units/wk to around 30
      units/wk in the advice group, whereas it remained between 50 and 60 units/wk in
      the control group (analysis of variance [ANOVA] F = 7.1, p less than 0.05). This
      was accompanied by falls in gamma-glutamyl transpeptidase (20.9%) and aspartate
      aminotransferase (18.1%), but no significant changes were seen in the control
      group. Standing diastolic blood pressure fell significantly in the advice group
      (from 101.5 mm Hg to 96.3 mm Hg) compared with the control group (ANOVA F = 4.8,
      p less than 0.05). The results suggest that advice to reduce alcohol consumption
      is a useful form of treatment for hypertensive patients who drink excessively.

PMID- 1346122
TI  - Effects of antihypertensive therapy on insulin resistance.
AB  - In view of the likely prohypertensive effects of hyperinsulinemia and the
      presence of insulin resistance in primary hypertension, the effects of various
      antihypertensive therapies on insulin sensitivity need to be identified. The
      evidence strongly supports major beneficial effects of weight reduction and
      aerobic exercise. Deleterious effects have been shown for diuretics and most beta
      blockers, whereas probable beneficial effects have been seen with alpha-blockers,
      one angiotensin converting enzyme inhibitor, and various calcium entry blockers.
      Improvement of insulin sensitivity and reduction of plasma insulin levels are
      desirable attributes of antihypertensive therapy that should be more carefully
      considered in the future.

PMID- 1346123
TI  - Comparison of hemagglutinating pili of Haemophilus influenzae type b with similar
      structures of nontypeable H. influenzae.
AB  - Thirty-eight clinical isolates of nontypeable Haemophilus influenzae were tested
      for the presence of hemagglutinating pili similar to those of H. influenzae type
      b (Hib) that mediate buccal epithelial cell adherence. Four endogenously
      hemagglutinating (HA+) strains were identified, and eight additional HA+ variants
      were obtained from HA- strains by erythrocyte enrichment. All 12 HA+ nontypeable
      H. influenzae isolates bound antisera directed against denatured pilins of Hib,
      but none bound antisera against assembled native pili of Hib. In erythrocyte- and
      buccal-cell-binding assays, HA+ nontypeable H. influenzae binding was reduced
      compared with HA+ Hib binding and was not significantly different from HA-
      nontypeable H. influenzae binding. Both HA- and HA+ nontypeable H. influenzae
      binding was increased over binding of HA- Hib. HA+ nontypeable H. influenzae
      strains agglutinated adult erythrocytes that possess the Anton antigen, which is
      thought to be the receptor for Hib pili, and did not agglutinate cord or Lu(a-b-)
      dominant erythrocytes, which lack the Anton antigen. Electron microscopy of HA-
      and HA+ variants of three nontypeable H. influenzae strains showed few or no
      surface appendages on the HA- organisms, but piluslike structures were seen on
      many organisms from two HA+ nontypeable H. influenzae strains and on a few
      organisms from one strain. Thus, nontypeable H. influenzae appears to possess
      structures that are immunologically similar to the pilins that make up the
      hemagglutinating pili of Hib. However, nontypeable H. influenzae appears to also
      possess mechanisms for erythrocyte and buccal cell adherence that are not
      directly correlated with the presence of a hemagglutinating pilus.

PMID- 1346124
TI  - Virulence of non-type 1-fimbriated and nonfimbriated nonflagellated Salmonella
      typhimurium mutants in murine typhoid fever.
AB  - The virulence of Salmonella typhimurium mutants that were unable to synthesize
      type 1 fimbriae was tested in a murine typhoid fever model. Nonfimbriated mutants
      (fim) exhibited a lower 50% lethal dose than a wild-type (fim+) strain and
      produced significantly higher mortality (fim, 55%; fim+, 37% [P less than 0.002])
      in mice that were challenged orally. There was no difference in virulence when
      the wild-type and mutant strains were injected intraperitoneally into mice. The
      progress of a short-term lethal infection was monitored after oral inoculation of
      mice with a mixture containing equivalent numbers of fim+ wild-type and fim
      mutant bacteria. The results indicated that while both strains colonized the
      intestinal tract equally well and invaded internal organs, the S. typhimurium fim
      mutant proliferated in the blood of the mice faster than the fim+ strain. The
      results of the mixed oral challenge suggested that bacteremia caused by fim+ S.
      typhimurium was reduced or delayed by the sequestration of the fimbriated
      bacteria in the spleen, liver, and kidneys. Thus, type 1 fimbriae were not
      virulence factors for S. typhimurium in this model, and the fimbriae may be an
      impediment to the pathogen in this setting. An S. typhimurium double mutant
      lacking type 1 fimbriae and flagella (fla) also was tested in mice. The virulence
      of the fim fla mutant was greatly reduced compared with that of the wild-type
      strain (mortality from fim fla challenge, 11% [P less than 0.0005]). The
      significance of this latter result is discussed in relation to host adaptation by
      pathogenic salmonellae.

PMID- 1346126
TI  - Effects of cholinergic and adrenergic agonists on adenylate cyclase activity of
      retinal microvascular pericytes in culture.
AB  - Pericytes are contractile cells that might help regulate microvascular blood
      flow. To understand their potential role in the regulatory responses of the
      retina and optic nerve head vessels, the response of pericytes isolated from
      bovine retinal microvessels was determined to oxotremorine, isoproterenol,
      phenylephrine, and clonidine. Isoproterenol doubled the basal levels of cyclic
      adenosine monophosphate (cAMP) specifically through beta-adrenergic receptors,
      because the effect was blocked by dl-propranolol. The alpha 1 agonist
      phenylephrine did not induce any major change in adenylate cyclase activity. The
      alpha 2 agonist clonidine decreased basal cAMP synthesis and reduced the effect
      of isoproterenol. The cholinergic agonist oxotremorine did not modify the basal
      activity of adenylate cyclase but was able to decrease by almost 50% the
      forskolin-induced increase of cAMP. These results suggest that pericytes have
      functional adrenergic and cholinergic receptors, and they might respond to
      autonomic vasoactive substances present in vivo.

PMID- 1346125
TI  - Avian P1 antigens inhibit agglutination mediated by P fimbriae of uropathogenic
      Escherichia coli.
AB  - Whole egg white from pigeon, dove, and cockatiel eggs, as well as the ovomucoid
      fraction of pigeon egg white, exhibited strong P1 antigenic activities and
      inhibited agglutination of human P1 erythrocytes and of digalactoside-coated
      latex beads by P-fimbriated Escherichia coli strains. In contrast, chicken egg
      white exhibited only weak P1 antigenic activity and had little impact on P
      fimbrial agglutination. These preparations did not affect hemagglutination by E.
      coli strains expressing mannose-resistant adhesins other than P fimbriae, i.e.,
      Dr, F1845, and S adhesins. Human anti-P1 serum diminished the P-fimbrial
      inhibitory activities of pigeon egg white and pigeon ovomucoid. Pigeon ovomucoid
      was equipotent on a molar basis with globoside, and the pigeon, dove, and
      cockatiel egg white preparations were equipotent with each other in P-fimbrial
      inhibition. Incubation of p erythrocytes in whole egg whites or in pigeon
      ovomucoid did not render them agglutinable by P-fimbriated bacteria, whereas
      incubation in globoside did. These data demonstrate that whole egg whites (and
      their ovomucoid fraction) from members of the families Columbidae (pigeons and
      doves) and Psittacidae (parrots) specifically and potently inhibit P-fimbrial
      agglutination, probably by providing P1 antigen as a receptor for the P-fimbrial
      adhesin. Avian egg white preparations may facilitate adhesin characterization of
      wild-type uropathogenic strains and may useful in preventing upper urinary tract
      infections due to P-fimbriated E. coli.

PMID- 1346128
TI  - A relationship between asparagine synthetase A and aspartyl tRNA synthetase.
AB  - A highly conserved protein motif characteristic of Class II aminoacyl tRNA
      synthetases was found to align with a region of Escherichia coli asparagine
      synthetase A. The alignment was most striking for aspartyl tRNA synthetase, an
      enzyme with catalytic similarities to asparagine synthetase. To test whether this
      sequence reflects a conserved function, site-directed mutagenesis was used to
      replace the codon for Arg298 of asparagine synthetase A, which aligns with an
      invariant arginine in the Class II aminoacyl tRNA synthetases. The resulting
      genes were expressed in E. coli, and the gene products were assayed for
      asparagine synthetase activity in vitro. Every substitution of Arg298, even to a
      lysine, resulted in a loss of asparagine synthetase activity. Directed random
      mutagenesis was then used to create a variety of codon changes which resulted in
      amino acid substitutions within the conserved motif surrounding Arg298. Of the 15
      mutant enzymes with amino acid substitutions yielding soluble enzyme, 13 with
      changes within the conserved region were found to have lost activity. These
      results are consistent with the possibility that asparagine synthetase A, one of
      the two unrelated asparagine synthetases in E. coli, evolved from an ancestral
      aminoacyl tRNA synthetase.

PMID- 1346127
TI  - Agonist response of human isolated posterior ciliary artery.
AB  - The isometric responses of isolated human posterior ciliary artery to adrenergic
      agonists, histamine (HIS), and 5-hydroxytryptamine (5-HT) were studied in
      passively stretched ring segments mounted in a myograph bath. Cumulative dose
      response curves were measured for nine agonists: HIS, 5-HT, dopamine (DOPA),
      epinephrine (A), norepinephrine (NA), tyramine (TYR), phenylephrine (PHE),
      isoproterenol (ISOP), and xylazine (XYL), and the log(molar concentration) at
      which one half of the maximum active tension was developed (EC50) was estimated.
      The ring segments were unresponsive to DOPA and XYL; HIS and ISOP produced
      biphasic responses with a mild relaxation for low concentrations and small
      contractions for high concentrations of the agonist. The remaining agonists
      caused contractile responses of magnitude listed in the rank order following
      compared with the maximum active tension in response to 0.124 M K(+)-Krebs: Kmax
      much greater than A greater than 5-HT = PHE greater than NA greater than TYR It
      was concluded that functional HIS, alpha 1-adrenergic, and 5-HT receptors were
      present on human posterior ciliary artery but that there are no alpha 2
      adrenergic receptors.

PMID- 1346129
TI  - Stimulation of protein synthesis in COS cells transfected with variants of the
      alpha-subunit of initiation factor eIF-2.
AB  - The role of eukaryotic initiation factor 2 (eIF-2) phosphorylation in
      translational control has been demonstrated in vivo by overexpressing variant
      forms of eIF-2 alpha that are not phosphorylated. COS-1 cells transiently
      transfected with expression vectors for human eIF-2 alpha contain 10-20-fold more
      eIF-2 alpha subunit than the endogenous COS cell eIF-2 trimeric complex.
      Expression of the variant form of eIF-2 alpha, Ser51Asp, where Asp replaces
      Ser51, causes inhibition of protein synthesis, whereas the Ser48Asp variant does
      not. When either Ser48 or Ser51 is replaced by Ala, the variants stimulate
      dihydrofolate reductase synthesis when the eIF-2 alpha kinase, DAI, is activated.
      In order to elucidate these mechanisms, we have separated eIF-2 trimeric
      complexes from free overexpressed eIF-2 alpha subunits by fast protein liquid
      chromatography Superose chromatography. Pulse-labeled cells transfected with wild
      type or variant DNAs produced eIF-2 preparations with greater than 10-fold higher
      specific radioactivity in the alpha-subunit compared to the gamma-subunit, thus
      demonstrating that the human eIF-2 alpha produced from the plasmids readily
      exchanges into COS cell eIF-2 complexes. Both wild-type and Ser48Ala variant
      forms of the free 2 alpha-subunit, further purified by MonoQ chromatography, are
      poor substrates for the heme-regulated eIF-2 alpha kinase, HRI, but are good
      substrates for double-stranded RNA-activated inhibitor in vitro; the Ser51Ala
      variant subunit is not phosphorylated by either kinase. None of the purified free
      eIF-2 alpha subunits inhibits phosphorylation of eIF-2 in vitro, even at up to 8
      fold molar excess. Examination of the extent of eIF-2 alpha phosphorylation in
      the COS cell eIF-2 complexes by two-dimensional polyacrylamide gel
      electrophoresis shows that the stimulation of dihydrofolate reductase synthesis
      by the Ser51Ala variant is most readily explained by failure of eIF-2 to be
      phosphorylated. Stimulation by the Ser48Ala variant appears to occur by
      mitigation of the effect of phosphorylation at Ser51 since the double variant,
      Ser48Ala-Ser51Asp, inhibits protein synthesis less than the single variant
      Ser51Asp. The evidence argues strongly against there being a second site of
      phosphorylation involved in translational repression.

PMID- 1346130
TI  - Heat sensitivity and Sp1 activation of complex formation at the Syrian hamster
      carbamoyl-phosphate synthase (glutamine-hydrolyzing)/aspartate
      carbamoyltransferase/dihydroorotase promoter in vitro.
AB  - To study the regulation of transcription of the carbamoyl-phosphate synthase
      (glutamine-hydrolyzing)/aspartate carbamoyltransferase/dihydroorotase (CAD) gene
      from the Syrian hamster, Mesocricetus auratus, we developed a homologous in vitro
      transcription system on the basis of nuclear extract from Syrian hamster kidney
      cells. We optimized the reaction temperature and the concentrations of DNA
      template, KCl, and MgCl2 simultaneously with the response surface method and
      found an unusually low temperature optimum of 20 degrees C. We therefore
      investigated whether CAD transcription in vitro depended on a heat-labile
      component of nuclear extract. Preincubating extract alone at 30 degrees C reduced
      transcription from the CAD promoter but not from the major late promoter of
      adenovirus 2. The formation of stable initiation complexes at the CAD promoter
      was diminished in heat-treated extract; run-off transcripts, however, accumulated
      at the same rate as in untreated extract. The heat sensitivity of complex
      formation correlated with the heat sensitivity of DNA binding by transcription
      factor Sp1, which binds to two sites in the CAD promoter; moreover, both
      preformed initiation complexes and DNA-bound Sp1 were heat-resistant. Adding
      purified Sp1 to heat-treated extract restored complex formation. We propose that
      Sp1 activates CAD transcription by stabilizing initiation complexes at the CAD
      promoter.

PMID- 1346131
TI  - Mammalian mitochondrial chaperonin 60 functions as a single toroidal ring.
AB  - Chaperonins are thought to participate in the process of protein folding in
      bacteria and in eukaryotic mitochondria and chloroplasts. While some chaperonins
      are relatively well characterized, the structures of the mammalian chaperonins
      are unknown. We have expressed a mammalian mitochondrial chaperonin 60 in
      Escherichia coli and purified the recombinant protein to homogeneity. Structural
      and biochemical analyses of this protein establish a single toroidal structure of
      seven subunits, in contrast to the homologous bacterial, fungal, and plant
      chaperonin 60s, which have double toroidal structures comprising two layers of
      seven identical subjects each. The recombinant mammalian chaperonin 60, together
      with the mammalian chaperonin 10 (but not with bacterial chaperonin 10),
      facilitates the formation of catalytically active ribulose-bisphosphate
      carboxylase from an unfolded state in the presence of K+ and MgATP. Analysis of
      the partial reactions involved in this in vitro reconstitution reveals that the
      single toroid of chaperonin 60 can form stable complexes with both unfolded or
      partially folded [35S]ribulose-bisphosphate carboxylase and mitochondrial (but
      not bacterial) chaperonin 10 in the presence of MgATP. We conclude that the
      minimal functional unit of chaperonin 60 is a single hepatmeric toroid.

PMID- 1346132
TI  - An initiation codon mutation in CD18 in association with the moderate phenotype
      of leukocyte adhesion deficiency.
AB  - Leukocyte adhesion deficiency (LAD) is an autosomal recessive disease caused by
      mutations in the CD18 gene which codes for the beta 2 integrin subunit. We
      studied two patients, the first of which had a moderate LAD phenotype and
      expressed only 9% of CD11/CD18 on blood leukocytes. RNA from lymphoblasts was
      reverse-transcribed, and the cDNA was amplified, cloned, and sequenced. An ATG to
      AAG alteration in the initiation codon was detected in 39 of 45 (87%) cDNA
      clones. This mutation was detected in the father, but not in the mother. The
      maternal defect was shown to be a frameshift mutation with the deletion of a
      single T in the aspartic acid codon at position 690 (GAT), 11 amino acids N
      terminal to the beginning of the transmembrane domain. This mutation predicts a
      polypeptide which would terminate without transmembrane or cytoplasmic domains.
      The frameshift mutation was also found in the second patient who had the severe
      phenotype of LAD (less than 1% of CD11/CD18), indicating that this allele does
      not encode a functional protein. The partial expression in the patient with a
      moderate phenotype must be derived from the initiation codon mutation and may be
      due to a low level of initiation of translation of the CD18 mRNA at the second
      codon (CUG).

PMID- 1346133
TI  - A single histidine in GABAA receptors is essential for benzodiazepine agonist
      binding.
AB  - Benzodiazepines (BZ) modulate neurotransmitter-evoked chloride currents at the
      gamma-aminobutyric acid type A (GABAA) receptor, the major inhibitory ion channel
      in the mammalian brain. This receptor is composed of structurally distinct
      subunits whose numerous molecular variants underlie the observed diversity in the
      properties of the BZ site. Pharmacologically distinct BZ sites can be recreated
      by the recombinant coexpression of any one of six alpha subunits, a beta subunit
      variant, and the gamma 2 subunit. In these receptors the alpha variant determines
      the affinity for ligand binding of the BZ site. Notably, the alpha 1 and alpha 6
      variants impart on alpha chi beta 2 gamma 2 receptors high and negligible
      affinity, respectively, to BZ ligands with sedative as well as anxiolytic
      activities. By exchanging domains between the alpha 1 and alpha 6 variants, we
      show that a portion of the large extracellular domain determines sensitivity
      toward these ligands. Furthermore, we identify a single histidine residue in the
      alpha 1 variant, replaced by an arginine in alpha 6, as a major determinant for
      high affinity binding of BZ agonists. This residue also plays a role in
      determining high affinity binding for BZ antagonists. Hence, this histidine
      present in the alpha 1, alpha 2, alpha 3, and alpha 5 subunits appears to be a
      key residue for the action of clinically used BZ ligands.

PMID- 1346134
TI  - Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid
      substitutions at a single site. Evidence for a region which constrains receptor
      activation.
AB  - Mutations in an intracellular region of the alpha 1B-adrenergic receptor
      constitutively activate the receptor, resulting in G protein coupling in the
      absence of agonist, as evidenced by elevated levels of polyphosphoinositide
      hydrolysis. Remarkably, all 19 possible amino acid substitutions at a single site
      in this region (alanine 293) confer constitutive activity. This set of mutated
      receptors exhibits a graded range of elevated biological activities, apparently
      representing a spectrum of receptor conformations which mimic the "active" state
      of the wild type receptor. In addition to their constitutive activities, these
      mutated receptors all demonstrate a higher affinity for agonists, another primary
      characteristic of the "active" conformation of G protein-coupled receptors. The
      fact that all possible mutations at this particular site result in increased
      activity suggests that this region may function to constrain the G protein
      coupling of the receptor, a constraint which is normally relieved by agonist
      occupancy.

PMID- 1346135
TI  - Different positively charged amino acids have similar effects on the topology of
      a polytopic transmembrane protein in Escherichia coli.
AB  - Integral membrane proteins from a wide variety of sources conform to a "positive
      inside rule," with many more positively charged amino acids in their cytoplasmic
      as compared to extracytoplasmic domains. A growing body of experimental work also
      points to positively charged residues in regions flanking the apolar
      transmembrane segments as being the main topological determinants. In this paper,
      we report a systematic comparison of the effects of positively (Arg, Lys, His) as
      well as negatively (Asp, Glu) charged residues on the membrane topology of a
      model Escherichia coli inner membrane protein. Our results show that positive
      charge is indeed the major factor determining the transmembrane topology, with
      Arg and Lys being of nearly equal efficiency. His, although normally a very weak
      topological determinant, can be potentiated by a lowering of the cytoplasmic pH.
      Asp and Glu affect the topology to similar extents and only when present in very
      high numbers.

PMID- 1346136
TI  - pH-dependent heterogeneity of acidic amino acid transport in rabbit jejunal brush
      border membrane vesicles.
AB  - Initial rates of Na(+)-dependent L-glutamic and D-aspartic acid uptake were
      determined at various substrate concentrations using a fast sampling, rapid
      filtration apparatus, and the resulting data were analyzed by nonlinear computer
      fitting to various transport models. At pH 6.0, L-glutamic acid transport was
      best accounted for by the presence of both high (Km = 61 microM) and low (Km =
      7.0 mM) affinity pathways, whereas D-aspartic acid transport was restricted to a
      single high affinity route (Km = 80 microM). Excess D-aspartic acid and L
      phenylalanine served to isolate L-glutamic acid flux through the remaining low
      and high affinity systems, respectively. Inhibition studies of other amino acids
      and analogs allowed us to identify the high affinity pathway as the X-AG system
      and the low affinity one as the intestinal NBB system. The pH dependences of the
      high and low affinity pathways of L-glutamic acid transport also allowed us to
      establish some relationship between the NBB and the more classical ASC system.
      Finally, these studies also revealed a heterotropic activation of the intestinal
      X-AG transport system by all neutral amino acids but glycine through an apparent
      activation of Vmax.

PMID- 1346137
TI  - Oxidative modification of Escherichia coli glutamine synthetase. Decreases in the
      thermodynamic stability of protein structure and specific changes in the active
      site conformation.
AB  - Metal catalyzed oxidation of specific amino acid residues has been proposed to be
      an important physiological mechanism of marking proteins for proteolytic
      degradation. After initial oxidative inactivation of dodecameric Escherichia coli
      glutamine synthetase (GS), the integrity of the GS active site and protein
      structure was assessed by monitoring ATP binding, observing a susceptibility of
      GS to tryptic cleavage, and comparative thermodynamic analysis. The tryptic
      cleavage rates of an active site linked central loop were significantly
      accelerated for the oxidized conformer. This tryptic cleavage was essentially
      prevented in the presence of glutamate for native GS but not for the oxidized
      conformer. The integrity of the ATP binding site in the oxidized GS was
      substantially altered as indicated by the reduction in fluorescence enhancement
      associated with ATP binding. Decreases in the free energies of quaternary protein
      structure and subunit interactions due to oxidative modification were determined
      by temperature and urea induced unfolding equilibrium measurements. Comparative
      thermal stability measurements of a partial unfolding transition indicated that
      the loss in stabilization free energy for the oxidized GS conformer was 1.3
      kcal/mol dodecamer. Under alkaline conditions, the urea-induced disruption of
      quaternary and tertiary structures of oxidized and native GS were examined. This
      comparative analysis revealed that the free energies of the subunit interactions
      and unfolding of the dissociated monomers for oxidized GS were decreased by 1.5
      and 1.7 kcal/mol, respectively. Our results suggest that small free energy
      decreases in GS protein structural stability of only 1-2 kcal/mol may be
      responsible for the selective proteolytic turnover of the oxidized GS.

PMID- 1346138
TI  - Beta-adrenergic, cAMP-mediated stimulation of proliferation of brown fat cells in
      primary culture. Mediation via beta 1 but not via beta 3 adrenoceptors.
AB  - The ability of adrenergic stimulation to affect the rate of DNA synthesis in
      mouse brown adipocyte precursor cells proliferating in primary culture was
      investigated. Addition of 1 microM norepinephrine to the cells at day 4 in
      culture (proliferating cells) significantly increased the rate of DNA synthesis,
      whereas no significant effect was seen at day 9 (confluent cells). The effect of
      norepinephrine could be mimicked by forskolin, cholera toxin, and by cAMP
      analogues. Specific [3H]thymidine incorporation (per unit of DNA) was reduced by
      norepinephrine stimulation, indicating saturation of the salvage pathway for dTTP
      synthesis already in unstimulated cells and implying a beta-adrenergic
      stimulation of dTTP synthesis. Pharmacological characterization of this effect
      indicated it was mediated by beta 1 receptors, with alpha 2 receptors exerting an
      opposing effect. Notably, the stimulation of DNA synthesis was not observed with
      the beta 3-specific agonist CGP-12177. In contrast, both norepinephrine and CGP
      12177 were able to induce the expression of the uncoupling protein thermogenin in
      the confluent cultured cells. This coincided with a shift in the cAMP-elevating
      potential of CGP-12177, from being antagonistic to norepinephrine stimulation in
      proliferating cells to being itself a full agonist in confluent cells, implying
      occurrence of coupled beta 3 receptors as part of the differentiation process. It
      was concluded that brown fat precursor cells respond directly to norepinephrine
      stimulation with an increased DNA synthesis, and that this response is mediated
      via the classical beta 1 receptors. This probably represents the cellular basis
      for the hyperplasia observed in the tissue in physiologically recruited states.

PMID- 1346140
TI  - Density-dependent regulation of cell surface gamma-glutamyl transpeptidase in
      cultured glial cells.
AB  - A decline in cell surface gamma-glutamyl transpeptidase specific activity was
      previously observed to be concomitant with C6 glial cell proliferation. To
      elucidate the underlying factor(s) mediating gamma-glutamyl transpeptidase down
      regulation, the effects of C6 cell density and culture conditions on cell surface
      transpeptidase activity levels were investigated. After 24 h of culture, the
      transpeptidase specific activities were inversely related to the initial plating
      densities. The lower-density cultures showed an induction within 24 h of plating.
      As the cultures proliferated, the specific transpeptidase activities declined to
      a common low level at post-confluency. The gamma-glutamyl transpeptidase down
      regulation was unrelated to cell growth rate and was most pronounced during
      logarithmic proliferation. Induction and down-regulation of gamma-glutamyl
      transpeptidase activity at low cell densities were not a result of
      trypsinization. Supplementation of low-density cultures with conditioned medium,
      use of matrix-coated wells, or periodic replacement of growth media to prevent
      conditioning had minor effects on the decline of cell surface activity. Kinetic
      analysis showed that the Michaelis constants and the reaction mechanism were
      unaltered by cell density, indicating that down-regulation was not due to
      allosteric factors or an alteration in enzyme character. A reduction in the
      maximal velocity of cell surface transpeptidation at higher cell densities
      suggested that gamma-glutamyl transpeptidase down-regulation is related to the
      concentration of enzyme at the cell surface. Immunocytochemical localization of
      gamma-glutamyl transpeptidase demonstrated that gamma-glutamyl transpeptidase
      antigen levels decrease as C6 cell density increases. These results led us to
      propose that cell-cell contact stimulates the disappearance of gamma-glutamyl
      transpeptidase from the surface of cultured C6 glial cells.

PMID- 1346139
TI  - Divalent cation regulation of the function of the leukocyte integrin LFA-1.
AB  - The integrin lymphocyte function-associated antigen-1 (LFA-1) expressed on T
      cells serves as a useful model for analysis of leukocyte integrin functional
      activity. We have assessed the role of divalent cations Mg2+, Ca2+, and Mn2+ in
      LFA-1 binding to ligand intercellular adhesion molecule-1 (ICAM-1) and induction
      of the divalent cation-dependent epitope recognized by mAb 24. Manganese strongly
      promoted both expression of the 24 epitope and T cell binding to ICAM-1 via LFA
      1, suggesting that Mn2+ is able to directly alter the conformation of LFA-1 in a
      manner that favors ligand binding. Since Mn2+ also promotes functional activity
      of other integrins, parallels in mechanism of ligand binding may span the
      integrin family. In contrast, induction of 24 epitope expression by Mg2+ required
      removal of Ca2+ from T cell LFA-1 with EGTA. Furthermore, binding of mAb 24 to T
      cell LFA-1 in the presence of either Mn2+ or Mg2+ was found to be specifically
      inhibited by Ca2+, suggestive of a negative regulatory role for Ca2+ in the
      control of leukocyte integrin function. Analysis of T cell binding to ICAM-1 via
      LFA-1 in the presence of Mg2+ or Mn2+, confirmed that Ca2+ exerted inhibitory
      effects upon LFA-1 function. The implication of our findings is that Ca2+ bound
      with relatively high affinity to LFA-1 may serve to maintain an inactive state.
      Thus induction of function and 24 epitope expression may occur as a result of
      displacement of Ca2+ from leukocyte integrins or alternatively, such activators
      may be able to impose the required conformational change in the presence of bound
      Ca2+.

PMID- 1346141
TI  - Loss of sperm in juvenile spermatogonial depletion (jsd) mutant mice is ascribed
      to a defect of intratubular environment to support germ cell differentiation.
AB  - C57BL/6(B6)-jsd/jsd mice are sterile due to the defective spermatogenesis in the
      testes. To know the cause of the deficient spermatogenesis in B6-jsd/jsd mice, we
      examined whether the problem is within or outside the seminiferous tubules by
      transplanting tubules from cryptorchid testes of B6- +/+ mice into B6-jsd/jsd
      testes or tubules from B6-jsd/jsd mice into testes of (WB x C57BL/6)F1-W/Wv
      (hereafter, WBB6F1-W/Wv) mice. Type A spermatogonia differentiated into
      spermatids in seminiferous tubules from cryptorchid testes transplanted into B6
      jsd/jsd testes. In contrast, in B6-jsd/jsd tubules transplanted into WBB6F1-W/Wv
      testes, type A spermatogonia were stimulated to mitotic proliferation, but didn't
      proceed to any differentiated germ cells. The present results suggest that the
      cause of the deficient spermatogenesis in B6-jsd/jsd mice is a defect of
      intratubular environment to support germ cell differentiation.

PMID- 1346142
TI  - Gastroesophageal reflux: diagnosis and management.
AB  - The pathologic potential of chronic esophagitis cannot be overemphasized.
      Persistent reflux causing cycles of mucosal damage followed by healing may
      eventually lead to end-stage disease, with development of peptic stricture. The
      most effective drugs available are those that inhibit acid production. Drugs that
      will enhance lower esophageal function are still in the future.

PMID- 1346143
TI  - Stimulated growth hormone (GH) secretion in children with delays in pubertal
      development before and after the onset of puberty: relationship with peripheral
      plasma GH-releasing hormone and somatostatin levels.
AB  - A reduced GH secretion has often been shown in prepubertal children with delays
      in pubertal development. In order to study the mechanism underlying this finding,
      we evaluated peripheral circulating levels of GH, GHRH, and somatostatin (SRIH)
      before and after the onset of sexual development in a group of eight late
      maturing children (six boys, two girls), comparing the results with those
      obtained in two groups of five prepubertal and four pubertal short children with
      familial short stature. GH was measured by a two-site immunoradiometric assay.
      Both GHRH and SRIH were assayed by specific RIAs after an acetone-petrolether
      extraction from plasma. Our data showed a significant increase (P less than
      0.001) in GH, GHRH, and SRIH levels (peak vs. basal values) in response to L-dopa
      administration in all groups. In pubertal children with delays in pubertal
      development GH and GHRH peak values (15.8 +/- 2.2 micrograms/L and 120 +/- 18
      pg/mL, respectively) were significantly greater (P less than 0.001) than in the
      same subjects before puberty (8.2 +/- 0.9 micrograms/L and 79 +/- 9 pg/mL,
      respectively), whereas SRIH peak values did not significantly change (41 +/- 6
      vs. 41 +/- 5 pg/mL; P = NS). Furthermore, prepubertal subjects with delays in
      pubertal development showed GH and GHRH peak values lower (P less than 0.001)
      than those of prepubertal subjects with FSS (13.3 +/- 1.8 micrograms/L and 120 +/
      13 pg/mL, respectively), whereas no statistical difference was present between
      the two groups of subjects after pubertal development (18.2 +/- 2.9 micrograms/L
      and 128 +/- 11 pg/mL, respectively). In conclusion, these findings support the
      assumption that in late maturing subjects during prepubertal period the decreased
      GH secretion may be ascribed to a reduced GHRH secretion, reversible with the
      onset of puberty, without change in circulating SRIH levels.

PMID- 1346144
TI  - Tumor necrosis factor beta gene polymorphisms in Graves' disease.
AB  - The physical mapping of tumor necrosis factor alpha (TNF alpha) and lymphotoxin
      (TNF beta) genes to the short arm of chromosome 6 in man between the loci for
      histocompatibility leucocyte antigens (HLA)-B and the complement system focused
      attention to this genetic region that controls immune responses in many ways. It
      also holds susceptibility genes for a variety of autoimmune disorders that are
      linked to specific alleles of loci in the HLA D subregion. We have recently
      identified a TNF restriction fragment length polymorphism with the enzyme NcoI
      (K. Badenhoop, G. Schwarz, J. Trowsdale, et al. Diabetologia. 1989;32:445-8). The
      less frequent fragment of 5.5 kilobase (kb) is in strong linkage disequilibrium
      with the HLA haplotype A1B8DR3. Since Graves' disease is linked to A1B8DR3, we
      analyzed TNF gene polymorphisms in a large group of Graves' disease patients and
      normal controls derived from four Centers. We show here a significant association
      of TNF beta polymorphisms with Graves' disease. The patients have less
      homozygotes for the 10.5 kb band (60 of 174, 34%) and more heterozygotes 10.5/5.5
      kb (96 of 174, 55%), than 173 controls (49% homozygotes 10.5 kb and 42%
      heterozygotes; chi 2 = 7.45, P less than 0.03). When DR3+ patients and controls
      were analyzed separately, heterozygotes were still significantly increased in
      DR3+ Graves' disease patients (54 of 77, 70%) compared to DR3+ controls (21 of
      45, 47%; chi 2 = 6.6, P less than 0.04). Furthermore, TNF fragment heterozygotes
      were found predominantly in patients, who had TSH-receptor antibodies (29/45,
      64%, P less than 0.007), implying that these patients might represent an
      immunogenetic subset of the disease. Although TNF beta polymorphisms are linked
      to A1B8DR3, these results suggest that they represent an additional
      susceptibility marker in Graves' disease.

PMID- 1346145
TI  - Presymptomatic testing using DNA markers for individuals at risk for familial
      multiple endocrine neoplasia 2A.
AB  - The carrier status of 39 at-risk individuals in 6 multiple endocrine neoplasia 2A
      families was determined using a DNA based test. We were able to calculate a
      virtual diagnosis (probability greater than 95%) for 77% of the individuals and a
      probable diagnosis (probability greater than 90%) for 90% of the individuals.
      This study points out some of the problems of specific pedigree structures that
      can affect the risk calculation. This study further shows that no single test
      based on either biochemistry, pathology, or genetics can consistently and
      unambiguously produce a presymptomatic diagnosis. We also describe two specific
      examples where DNA testing has helped to resolve clinical uncertainties in at
      risk individuals.

PMID- 1346147
TI  - Twentieth Annual International Neuropsychological Society Meeting. February 5-8,
      1992, San Diego, California. Abstracts.

PMID- 1346146
TI  - Differential changes in alpha- and beta-adrenoceptor linked [45Ca2+] uptake in
      platelets from patients with anorexia nervosa.
AB  - [45Ca2+] Uptake was studied in response to adrenaline, isoprenaline,
      noradrenaline, and (Bu)2cAMP in platelets from patients with anorexia nervosa. In
      both controls and anorectics, adrenaline, isoprenaline, noradrenaline, and
      (Bu)2cAMP stimulated [45Ca2+] uptake. In receptor subtype characterisation
      studies on control platelets, adrenaline-stimulated [45Ca2+] uptake was blocked
      by yohimbine (an alpha 2-adrenoceptor antagonist) and the specific beta 2
      adrenoceptor antagonist ICI 118,551, but not by atenolol (a beta 1-antagonist).
      Isoprenaline action was blocked by ICI 118,551, but not by yohimbine.
      Noradrenaline-stimulated [45Ca2+] uptake was blocked by yohimbine but not by ICI
      118,551. In platelets from anorectic patients, there was a significant increase
      in noradrenaline-stimulated [45Ca2+] uptake, a significant diminution in
      adrenaline and isoprenaline-stimulated [45Ca2+] uptake, but no significant
      difference in (Bu)2cAMP-stimulated [45Ca2+] uptake, when compared with controls.
      Basal uptake was also significantly enhanced in anorectics and was found to be
      inhibited with verapamil but not adrenoceptor antagonist. These data firstly
      indicate that both alpha 2- and beta 2-adrenoceptor activation elicits [45Ca2+]
      uptake by platelets. It is proposed that this stimulated [45Ca2+] uptake does not
      reflect changes in cytosolic Ca2+ but to localized changes of Ca2+ at the plasma
      membrane, possibly associated with receptor activation, per se. The respective
      increase and decrease of alpha- and beta-adrenoceptor activity in platelets from
      anorectic patients is in accord with other reports of changes of adrenoceptor
      number and type in platelets and other cells from anorectic patients. There may
      also be an increase in calcium channel activity in platelets from anorectics.

PMID- 1346148
TI  - Elevation of IgE in HIV-infected subjects: a marker of poor prognosis.
AB  - The IgE synthesis is tightly controlled by a complex network of T and B cells.
      Because human immunodeficiency virus (HIV) disease associates T cell activation
      and depletion, polyclonal B cell activation, atopic symptoms, drug
      hypersensitivity, and autoimmune activity, we have evaluated IgE, as well as IgA,
      IgG, and IgM, in 315 HIV-seropositive individuals with or without acquired
      immunodeficiency syndrome (AIDS) and compared the results to those of 100 HIV
      seronegative subjects. IgE levels were higher in HIV-infected subjects as a
      whole, compared to levels in seronegative control subjects (p less than 0.05).
      This difference was particularly marked between patients with AIDS and control
      subjects (p less than 0.005). A strong relationship appeared between IgE and the
      immune status as assessed by CD4 cell counts (p less than 0.001 between IgE
      values in patients with CD4 less than 300 or greater than 300/microliters). In
      addition, we assessed the predictive value of IgE elevation over disease
      progression: in subjects with a CD4 count less than 300/microliters, the survival
      analysis disclosed a 24-month occurrence rate of AIDS of 83% in individuals with
      IgE greater than 150 KIU/L versus 44% in individuals with IgE less than 150 (p =
      0.016). In subjects with an AIDS-related complex, IgE greater than 150 indicated
      a 100% rate of AIDS versus 9% in individuals with IgE less than 150 (p = 0.003).
      Thus, IgE levels appear to be a very discriminative marker between patients in
      late stages of HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346149
TI  - Metabolic half-life of somatostatin and peptidase activities are altered in
      Alzheimer's disease.
AB  - Several reports have described decreased immunoreactive somatostatin levels in
      specific regions of post-mortem brain tissue from patients diagnosed with senile
      dementia of the Alzheimer type (SDAT). In an attempt to determine if the
      metabolism of somatostatin is also altered as a result of SDAT, we examined the
      regional metabolic half-life of somatostatin-28 (SS-28) and somatostatin-14 (SS
      14). The activity of the following peptidases was also determined: neutral
      endopeptidase E.C. 3.4.24.11; metalloendopeptidase E.C. 3.4.24.15;
      carboxypeptidase E (E.C. 3.4.17.10); and trypsin-like serine protease. The
      metabolic half-life of SS-28 was significantly reduced in post-mortem Brodmann
      Area 22 of SDAT tissue. This decrease in SS-28 metabolic half-life was correlated
      with a significant increase in trypsin-like serine protease activity in the same
      SDAT brain region. The formation rate of SS-14 from SS-28 incubated with Brodmann
      Area 22 homogenates was also increased in SDAT tissues as compared to controls. A
      regional variation in neutral endopeptidase E.C. 3.4.24.11 was also noted in both
      controls and SDAT samples. Although postmortem intervals of samples varied
      significantly, no effect was seen on any biochemical parameter measured. Results
      from this study provide evidence that a correlation can be made between changes
      in metabolic half-life somatostatin and alterations in neuropeptidase activities
      due to SDAT. As these data show alterations in both proteolytic metabolism and
      peptidase activities, many other biologically active peptide substrates could
      also be affected in SDAT.

PMID- 1346150
TI  - Intercellular adhesion molecule-2, a second counter-receptor for CD11a/CD18
      (leukocyte function-associated antigen-1), provides a costimulatory signal for T
      cell receptor-initiated activation of human T cells.
AB  - Activation of T cells often requires both activation signals delivered by
      ligation of the TCR and those resulting from costimulatory interactions between
      certain T cell surface accessory molecules and their respective counter-receptors
      on APC. CD11a/CD18 complex on T cells modulate the activation of T cells by
      interacting with its counter-receptors intracellular adhesion molecule (ICAM-1)
      (CD54) and/or ICAM-2 on the surface of APC. The costimulatory ability of ICAM-1
      has been demonstrated. Using a soluble ICAM-2 Ig fusion protein (receptor
      globulin, Rg) we demonstrate the costimulatory effect of ICAM-2 during the
      activation of CD4+ T cells. When coimmobilized with anti-TCR-1 mAb ICAM-2 Rg
      induced vigorous proliferative response of CD4+ T cells. This costimulatory
      effect of ICAM-2 was dependent on its coimmobilization with mAb directed at the
      CD3/TCR complex but not those directed at CD2 or CD28. Both resting as well as Ag
      primed CD4+ T cells responded to the costimulatory effects of ICAM-2. The
      addition of mAb directed at the CD11a or CD18 molecules almost completely
      inhibited the responses to ICAM-2 Rg. These results are consistent with the role
      of CD11a/CD18 complex as a receptor for ICAM-2 mediating its costimulatory
      effects. Stimulation of T cells with coimmobilized anti-TCR-1 and ICAM-2 resulted
      in the induction of IL-2R (CD25), and anti-Tac (CD25) mAb inhibited this response
      suggesting the contribution of endogenously synthesized IL-2 during this
      stimulation. These results demonstrate that like its homologue ICAM-1, ICAM-2
      also exerts a strong costimulatory effect during the TCR-initiated activation of
      T cells. The costimulatory effects generated by the CD11a/CD18:ICAM-2 interaction
      may be critical during the initiation of T cell activation by ICAM-1low APC.

PMID- 1346151
TI  - Autoreactivity of low but not of high CD4 variants of an antigen-specific, I-A
      restricted mouse T cell clone.
AB  - Variant lines expressing high and low surface densities of the accessory molecule
      CD4 have been developed by repeated preparative flow cytometric cell sortings
      from the murine Th cell clone D10.G4.1 (D10). The high CD4 variant line (D10H)
      fully maintained the original I-Ak restricted specificity for conalbumin of wild
      type D10 cells. In contrast, the low CD4 variant line (D10L) showed a strong
      autoreactivity to I-Ak carrying stimulator cells alone which was only slightly
      augmented by addition of conalbumin. Cell surface molecules other than CD4,
      including TCR, CD3, CD11a, CD2, CD45, CD44, and MHC class I, remained identical
      on D10H and D10L sublines as on D10 wild-type cells. The possibility that D10L
      cells had suffered alterations of their TCR-alpha beta was excluded by
      demonstrating their reactivity with a panel of eight different anti-clonotypic
      mAb specific for various epitopes of the D10 TCR. By limiting dilution analysis
      we show that the majority of responding cells of D10L sublines were autoreactive.
      Although the reactivity for allogeneic I-A also increased as compared with D10H
      cells, a clear preference for self-I-Ak was maintained so that a true
      autoreactive phenotype was evident. The results indicate that the surface
      concentration of CD4 has a decisive influence on self-non-self discrimination of
      MHC class II-restricted Th cells.

PMID- 1346152
TI  - CD4+ lymphocyte cell enumeration for prediction of clinical course of human
      immunodeficiency virus disease: a review.
AB  - Over the last 10 years the appreciation of the full breadth of the spectrum of
      human immunodeficiency virus (HIV) infection has gradually increased; it is now
      known that AIDS represents merely the end stage of this progressive infectious
      process. The surrogate marker that most closely correlates with the stage of HIV
      infection is the CD4+, or T helper, cell count. Because this count is relied on
      in making important therapeutic decisions, it is of paramount importance that
      clinicians be cognizant of and fully understand the multiple factors that can
      influence this parameter: the variability of the count from day to day and from
      morning to night, the influence of intercurrent viral infections, the influence
      of drugs. In this AIDS Commentary, Sten H. Vermund and his colleagues at the
      National Institutes of Health discuss these issues and put the CD4+ cell count
      into a lucid and practical clinical perspective.

PMID- 1346153
TI  - Signaling by lymphocyte function-associated antigen 1 (LFA-1) in B cells:
      enhanced antigen presentation after stimulation through LFA-1.
AB  - To examine the role of lymphocyte function-associated antigen 1 (LFA-1)
      expression on murine B cells as it pertains to their function in T cell
      activation, we carried out antigen-presentation assays in tissue culture wells
      coated with a purified, secreted form of the murine intercellular adhesion
      molecule 1 (ICAM-1). We observed a significant decrease in the concentration of
      antigen required to activate a T cell hybridoma and primary T cells in wells
      coated with ICAM-1. This effect was dependent on the amount of ICAM-1 used to
      coat the wells and was also observed in wells coated with anti-LFA-1-monoclonal
      antibodies and was blocked by soluble anti-LFA-1 antibodies. The effect on
      antigen dose was most pronounced in assays carried out with an ICAM-1-deficient
      mutant B lymphoma cell line, small resting primary B cells, and unfractionated
      primary B cells at low concentrations. No decrease in the antigen dose was
      observed if the B cells were chemically fixed or treated with ricin, or when
      antigen was presented by a HeLa cell line transfected with murine class II major
      histocompatibility complex (MHC) genes, indicating that the immobilized ICAM-1
      was mediating its effect through B cell LFA-1, and that B cell protein synthesis
      was required. The enhancing effect was also observed if the B cells were
      prepulsed with antigen, indicating that improved uptake or processing of antigen,
      or increased class II MHC expression were unlikely mechanisms.

PMID- 1346154
TI  - Searching for hematopoietic stem cells: evidence that Thy-1.1lo Lin- Sca-1+ cells
      are the only stem cells in C57BL/Ka-Thy-1.1 bone marrow.
AB  - Hematopoietic stem cells (HSCs) are defined in mice by three activities: they
      must rescue lethally irradiated mice (radioprotection), they must self-renew, and
      they must restore all blood cell lineages permanently. We initially demonstrated
      that HSCs were contained in a rare (approximately 0.05%) subset of bone marrow
      cells with the following surface marker profile: Thy-1.1lo Lin- Sca-1+. These
      cells were capable of long-term, multi-lineage reconstitution and radioprotection
      of lethally irradiated mice with an enrichment that mirrors their representation
      in bone marrow, namely, 1,000-2,000-fold. However, the experiments reported did
      not exclude the possibility that stem cell activity may also reside in
      populations that are Thy-1.1-, Sca-1-, or Lin+. In this article stem cell
      activity was determined by measuring: (a) radioprotection provided by sorted
      cells; (b) long-term, multi-lineage reconstitution of these surviving mice; and
      (c) long-term, multi-lineage reconstitution by donor cells when radioprotection
      is provided by coinjection of congenic host bone marrow cells. Here we
      demonstrate that HSC activity was detected in Thy-1.1+, Sca-1+, and Lin-
      fractions, but not Thy-1.1-, Sca-1-, or Lin+ bone marrow cells. We conclude that
      Thy-1.1lo Lin- Sca-1+ cells comprise the only adult C57BL/Ka-Thy-1.1 mouse bone
      marrow subset that contains pluripotent HSCs.

PMID- 1346156
TI  - Defective RNAs in mosquito cells persistently infected with Bunyamwera virus.
AB  - Viral protein and RNA synthesis were compared in BHK and Aedes albopictus C6/36
      (mosquito) cells infected with Bunyamwera virus. In BHK cells host protein
      synthesis was inhibited and viral proteins were detected until the cells died; in
      C6/36 cells there was little inhibition of host proteins and viral proteins could
      not be detected after 36 h post-infection. Relatively more S segment RNA than L
      or M segment RNA was produced in infected C6/36 cells compared to BHK cells. A
      persistent infection of C6/36 cells was established and the cells were passaged
      at weekly intervals for over a year. The titre of virus released from the cells
      and the level of viral RNA in the cells at different passages fluctuated
      markedly, but there was no simple relationship between virus titre and the amount
      of viral RNA. Northern blot analysis of viral RNA extracted from persistently
      infected cells revealed the presence of subgenomic RNAs derived from the L RNA
      segment. These defective RNAs were not packaged into nucleocapsids. The presence
      of the defective RNAs did not correlate with resistance of cells cloned from the
      persistently infected population to superinfection with homologous virus. Hence
      the role of these defective RNAs in the maintenance of the persistent state
      remains to be elucidated.

PMID- 1346155
TI  - Development of humanized bispecific antibodies reactive with cytotoxic
      lymphocytes and tumor cells overexpressing the HER2 protooncogene.
AB  - The HER2 protooncogene encodes a 185-kD transmembrane phosphoglycoproteins, human
      epidermal growth factor receptor 2 (p185HER2), whose amplified expression on the
      cell surface can lead to malignant transformation. Overexpression of
      HER2/p185HER2 is strongly correlated with progression of human ovarian and breast
      carcinomas. Recent studies have shown that human T cells can be targeted with
      bispecific antibody to react against human tumor cells in vitro. We have
      developed a bispecific F(ab')2 antibody molecule consisting of a humanized arm
      with a specificity to p185HER2 linked to another arm derived from a murine anti
      CD3 monoclonal antibody that we have cloned from UCHT1 hybridoma. The antigen
      binding loops for the anti-CD3 were installed in the context of human variable
      region framework residues, thus forming a fully humanized BsF(ab')2 fragment.
      Additional variants were produced by replacement of amino acid residues located
      in light chain complementarity determining region 2 and heavy chain framework
      region 3 of the humanized anti-CD3 arm. Flow cytometry analysis showed that the
      bispecific F(ab')2 molecules can bind specifically to cells overexpressing
      p185HER2 and to normal human peripheral blood mononuclear cells bearing the CD3
      surface marker. In additional experiments, the presence of bispecific F(ab')2
      caused up to fourfold enhancement in the cytotoxic activities of human T cells
      against tumor cells overexpressing p185HER2 as determined by a 51Cr release
      assay. These bispecific molecules have a potential use as therapeutic agents for
      the treatment of cancer.

PMID- 1346157
TI  - Spinal subdural abscess. Case report.
AB  - Only 44 cases of spinal subdural abscess have been reported to date. The authors
      present another case and review the relevant literature. The findings of
      intraspinal gassification on computerized tomography scans and Escherichia coli
      as the causative organism have not previously been described in relation to
      spinal subdural abscess. Most frequently, Staphylococcus aureus is the
      responsible organism. Hematogenous spread of infection from a distant source
      often takes place. In a surprising number of incidences, iatrogenic causes are
      the primary foci of spinal subdural abscess. Spinal subdural abscess is an
      unpredictable disease, with an unfavorable outcome if left untreated. If there is
      suspicion of a spinal subdural abscess, urgent radiological examination followed
      by immediate surgical drainage and appropriate antibiotic therapy is warranted.

PMID- 1346159
TI  - Characterization of receptors involved in dopamine-induced activation of
      phospholipase-C in rat renal cortex.
AB  - Dopamine (DA) is reported to stimulate phospholipase-C (PL-C) in rat renal
      cortex. Inasmuch as DA activates alpha adrenoceptors and DA receptors, the
      relative contribution of these receptors to DA-induced activation of PL-C is not
      yet established. We examined the effect of DA on PL-C activity in rat renal
      cortical slices prelabeled with myo-2-[3H]inositol in the presence of Li+. PL-C
      activity was expressed as fractional release (FR) of combined [3H]inositol
      phosphates expressed as dpm inositol phosphates accumulated/total dpm
      incorporated X 100. DA (1 mM) produced time-dependent increases in FR up to 60
      min. DA (1, 3 and 10 mM) produced 61%, 88% and 110% increases in FR over control.
      When DA was given in the presence of SCH 23390, a selective DA-1 receptor
      antagonist, the increase in FR was significantly reduced to 33%, 51% and 62%,
      respectively, but the increase in FR remained unaffected in the presence of a DA
      2 receptor antagonist, domperidone (30 microM). Phentolamine (10 microM) also
      inhibited the response to DA to 41%, 47% and 43% at the respective
      concentrations. DA-induced stimulation of PL-C was completely abolished in the
      combined presence of both SCH 23390 (30 microM) and phentolamine (10 microM). SCH
      23390, domperidone or phentolamine alone did not significantly change the basal
      PL-C activity in renal cortical slices. These results demonstrate that 1) DA
      stimulates PL-C in rat renal cortex via activation of both DA-1 receptors and
      alpha adrenoceptors and DA-2 receptors are not involved in this response; and 2)
      during normal sodium intake, intrarenal DA does not modulate the PL-C activity in
      rat renal cortex.

PMID- 1346158
TI  - A proposed mechanism of action for the antinociceptive effect of intrathecally
      administered calcium in the mouse.
AB  - Administration of i.t. calcium has been shown to produce effects which are
      opposite to those observed when calcium is injected into the brain. The purpose
      of this study was to elucidate the mechanism of the antinociceptive action of
      calcium (i.t.). Injection of calcium (i.t.) produced antinociceptive effects in
      the tail-flick and p-phenylquinone (PPQ) stretching tests. The ED50 value for
      calcium (i.t.) in the PPQ test was 4.8 (4.2-5.5) nmol per mouse vs. 344 (251-469)
      nmol per mouse for calcium (i.t.) in the tail-flick test. The antinociceptive
      effects of calcium (i.t.) were attenuated significantly in the tail-flick test by
      pretreatment with naloxone (i.t.) (AD50 value = 200 pmol/mouse) and ICI-174,864
      (i.t.) (AD50 value = 20 nmol/mouse), but not by the kappa receptor-selective
      antagonist nor-BNI. The antinociceptive effects of calcium (i.t.) were attenuated
      significantly in the PPQ test by pretreatment with naloxone (i.t.) (AD50 value =
      50 pmol/mouse) and norbinaltorphimine (i.t.) (AD50 value = 110 pmol/mouse), but
      not by the delta receptor-selective antagonists naltrindole and ICI-174, 864.
      Administration of calcium (i.t.) significantly enhanced the antinociceptive
      effects of mu [D-Ala2,N-Me-Phe4,Gly-ol]enkephalin, delta [D-Pen2,D
      Pen5]enkephalin and kappa (U50,488H) opioid receptor-selective peptides. The
      injection of the dibutyryl derivative of cyclic AMP (i.t.), as well as forskolin
      (i.t.), blocked the antinociceptive effects of calcium (i.t.) (AD50 values = 39
      nmol and 1.7 nmol/mouse, respectively). Injection of apamin (AD50 value = 2.9
      pmol/mouse) and charybodotoxin (58 fmol/mouse), blockers of calcium-gated
      potassium channels, significantly blocked calcium (i.t.). The antinociceptive
      effects of calcium (i.t.) were also blocked by verapamil (30 and 60 nmol/mouse),
      theophylline (275 nmol/mouse) and substance P (7.4 nmol/mouse, i.t.). Thus, the
      data indicate that the mechanism underlying the antinociceptive effect of calcium
      (i.t.) involves mediation, at least in part, by opioid peptides, alterations in
      intraneuronal cyclic AMP and/or neuronal hyperpolarization, and decreased release
      of substance P. The administration of calcium (i.t.) may also enhance the release
      of adenosine as a significant factor in the antinociceptive effects of the
      calcium.

PMID- 1346160
TI  - Evidence for a noradrenergic innervation to "atypical" beta adrenoceptors (or
      putative beta-3 adrenoceptors) in the ileum of guinea pig.
AB  - Indirect evidence suggests that beta-1 adrenoceptors in the guinea pig ileum are
      innervated but it has not been determined whether "atypical" beta adrenoceptors
      also receive a postganglionic sympathetic innervation. To answer this question,
      experiments were undertaken using electrical stimulation of para-arterial
      sympathetic neurons to evoke relaxation in isolated segments of guinea pig ileum.
      Tension was developed in the ileal segments by either transmural electrical field
      stimulation to evoke the cholinergic "twitch" response, or by histamine to
      produce a steady-state contracture. Para-arterial sympathetic nerve stimulation
      evoked a frequency-dependent inhibition of the twitch response which was blocked
      by guanethidine and restored by dexamphetamine, indicating typical noradrenergic
      transmission. In preparations contracted with histamine and pretreated with
      benextramine to block alpha adrenoceptors, para-arterial sympathetic nerve
      stimulation evoked frequency-dependent relaxations which were reduced in
      magnitude but not abolished by the following beta adrenoceptor antagonists:
      bromoacetylalprenololmenthane (1 microM) or a combination of ICI 118,551 (0.3
      microM) and CGP 20712A (0.1 microM). Remaining responses were blocked by
      compounds exhibiting affinity for atypical beta adrenoceptors, (-)-alprenolol (3
      microM) and nadolol (300 microM), as well as the agonist (-)-isoproterenol (10
      microM; to saturate the atypical beta adrenoceptor). However, relaxations to
      papaverine were unaffected by these treatments. Experiments revealed that
      potential cotransmitters (ATP, neuropeptide Y and somatostatin) do not appear to
      play a detectable role in relaxations produced by para-arterial sympathetic nerve
      stimulation. The results demonstrate, for the first time, that atypical beta
      adrenoceptors in guinea pig ileum receive a noradrenergic innervation.

PMID- 1346161
TI  - Effect of fenoldopam on the acute and subacute nephrotoxicity produced by
      amphotericin B in the dog.
AB  - The effect of the selective dopamine DA1 receptor agonist fenoldopam (1
      microgram/kg/min i.v.) on the acute nephrotoxic response to amphotericin B (2
      mg/kg i.v.) has been studied in the anesthetized dog. Animals were prepared for
      the measurement of blood pressure, renal blood flow, urine flow, glomerular
      filtration rate and sodium and potassium excretion. Amphotericin B was given over
      20 min and the animals were followed for an additional 160 min. The fenoldopam
      infusion was started 20 min before amphotericin B and was continued for the
      duration of the experiment. In control animals, amphotericin B markedly increased
      renal vascular resistance without affecting blood pressure and thus produced a
      significant reduction in renal blood flow. The renal vasoconstrictor response to
      amphotericin B was not attenuated by fenoldopam. Concomitant with the renal
      vasoconstriction produced by amphotericin B was a marked reduction in glomerular
      filtration rate, sodium excretion and urine flow rate, which lasted for at least
      160 min after amphotericin B treatment. Fenoldopam did not have any effect on the
      initial reductions in glomerular filtration rate, sodium excretion and urine flow
      rate but did produce a significant return of these parameters toward control
      levels by 160 min, despite the continued renal vasoconstriction. The effect of
      fenoldopam (0.5 microgram/kg/min) given continuously by i.v. infusion on the
      subacute nephrotoxic response produced by amphotericin B given every other day
      for 8 days was also investigated. One day after the start of the fenoldopam
      infusion, venous samples were drawn for the analysis of serum creatinine and
      blood urea nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346162
TI  - Differential inhibition of cholinergic and noncholinergic neurogenic contractions
      by 5-hydroxytryptamine1A receptor agonists in guinea pig ileum.
AB  - Previous studies have shown that 5-hydroxytryptamine1A (5-HT1A) receptors are
      localized only to a subset of myenteric neurons in guinea pig ileum; the purpose
      of this study was to determine the possible functional significance of this
      differential receptor localization. Nerve-mediated contractions of the
      longitudinal muscle, myenteric plexus of guinea pig ileum were studied in vitro.
      Contractions were evoked by single transmural electrical stimuli (0.5-msec
      duration, at 0.1 Hz; cholinergic) or trains of stimuli (10 or 20 Hz for 1 sec;
      noncholinergic; scopolamine, 1 microM present). The 5-HT1A agonist, 8-hydroxy-2
      (n-dipropylamino)tetralin (DPAT), reduced cholinergic contractions by no more
      than 14% in the concentration range of 0.001 to 0.3 microM. At high
      concentrations (1 to 100 microM), DPAT inhibited longitudinal muscle, myenteric
      plexus contractions; the EC50 was 6 microM. 5-Hydroxytryptamine (5-HT) and 5
      carboxamidotryptamine (5-CT) reduced longitudinal muscle, myenteric plexus
      contractions by a maximum of 35% and 24% at 100 and 30 microM, respectively.
      Spiperone and 1-(2-methoxyphenyl)-4-[4-(2-phthalimidobutyl]piperazine (NAN-190),
      two 5-HT1A receptor antagonists, did not block DPAT-induced inhibition of
      cholinergic contractions. DPAT (3, 10 and 30 microM) shifted histamine
      concentration-response curves to the right in an apparently competitive manner;
      Schild analysis yielded a pA2 of 5.2. DPAT (3, 10, 30 and 100 microM) also
      shifted bethanechol concentration-response curves to the right in an apparently
      competitive manner; Schild analysis yielded a pA2 of 5.5. These data indicate
      that DPAT blocks histamine and muscarinic receptors on longitudinal
      muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346163
TI  - Cholecystokinin release from the rat caudate-putamen, cortex and hippocampus is
      increased by activation of the D1 dopamine receptor.
AB  - Studies were undertaken to examine the role of dopamine in the regulation of
      cholecystokinin (CCK) release in slices of the rat caudate-putamen (CP), a region
      where both neuroactive substances are abundant yet not extensively colocalized.
      It was found that dopamine, acting through a D1 dopamine receptor, is a major
      factor regulating CCK release in this tissue. Haloperidol and the selective D1
      antagonist, SKF 83566, but not the D2 antagonist, sulpiride, inhibited potassium
      evoked release from CP slices. Apomorphine enhanced both basal and potassium
      evoked release, an effect which was reversed by (+/-)SKF 83566, but not by
      sulpiride. The D1 agonist, (+)SKF 38393, displayed agonist and antagonist
      activity in this system, whereas the D2 agonist, quinpirole, had no effect.
      Depletion of endogenous dopamine by pretreatment of animals with alpha-methyl
      para-tyrosine decreased potassium-induced release by 45%, and in these animals,
      haloperidol no longer inhibited release. These dopaminergic agents altered CCK
      release in cortex and hippocampus in a similar fashion, although those tissues
      were less sensitive to their effects. These results suggest that dopamine, acting
      through D1 receptors, increases CCK release in CP, cortex and hippocampus. The
      results of previous studies showing that phorbol esters increase CCK release and
      that occupation of D1 receptors increases phosphoinositol turnover make it
      possible to hypothesize that dopamine, acting through D1 receptors, is increasing
      CCK release by increasing phosphoinositol turnover. Further studies will be
      required to verify this hypothesis and to determine whether dopamine is acting
      directly or indirectly to modulate CCK release.

PMID- 1346164
TI  - Captopril and ANP: changes in renal hemodynamics, glomerular-ANP receptors and
      guanylate cyclase activity in rats with heart failure.
AB  - To define the renal effects of atrial natriuretic peptide (ANP) in heart failure,
      we studied rats with heart failure after coronary artery ligation. The rats
      received either captopril (2 milligrams drinking water) or placebo for 4 weeks.
      Glomerular filtration rate, renal plasma flow, filtration fraction, urine volume,
      urinary sodium excretion and the percent fractional excretion of sodium were
      measured before and after an infusion of ANP (0.3 microgram/kg/min). To determine
      whether changes in ANP receptor binding and responsiveness occur in heart failure
      and after captopril treatment, we performed radioreceptor binding studies and
      measured guanylate cyclase activity. Atrial natriuretic peptide in sham-operated
      rats decreased mean arterial pressure from 118 +/- 5 to 95 +/- 5 mm Hg (P less
      than .001), increased urine volume from 0.06 +/- 0.02 to 0.16 +/- 0.05 ml/min/kg
      (P less than .05), urinary sodium excretion, 14.2 +/- 3.1 to 41.4 +/- 8.9 mu
      eq/min/kg (P less than .02), filtration fraction from 0.30 +/- 0.03 to 0.40 +/-
      0.4 (P less than .05), and the percent fractional excretion of sodium from 0.84
      +/- 0.19 to 2.85 +/- 0.61 (P less than .02). Atrial natriuretic peptide in
      untreated rats with heart failure produced no significant systemic or renal
      hemodynamic effects. In rats with heart failure treated with captopril, ANP
      decreased mean arterial pressure from 93 +/- 4 to 86 +/- 4 mm Hg (P less than
      .05) and increased hematocrit from 50 +/- 2 to 52 +/- 1 (P less than
      .001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346165
TI  - Opposite effects of NMDA receptor blockade on dopaminergic D1- and D2-mediated
      behavior in the 6-hydroxydopamine model of turning: relationship with c-fos
      expression.
AB  - In rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal
      dopaminergic pathway, I-dihydroxyphenylalanine (L-DOPA) induces contralateral
      turning through activation of denervated D1 and D2 receptors. Blockade of N
      methyl-D-aspartate (NMDA) receptors by the noncompetitive antagonist (+)MK-801
      (0.1 mg/kg, i.p.), potentiated L-DOPA-induced contralateral turning. In 6-OHDA
      lesioned rats, selective agonists of D1 (SKF 38393, CY 208-243) or D2 (LY 171555)
      receptors also induce contralateral turning; however, (+)MK-801 pretreatment,
      although markedly potentiating D1, almost completely inhibited D2-mediated
      turning. The potentiation of SKF 38393-induced contralateral turning by MK-801
      was stereospecific and was observed also with the noncompetitive NMDA antagonist
      phencyclidine, and with the competitive antagonist CPP. Administration of the D1
      antagonist SCH 23390 (0.1 mg/kg s.c.) blocked (+)MK-801-induced potentiation of L
      DOPA contralateral turning, confirming the D1 nature of the effects observed.
      Expression of the early gene c-fos in the caudate-putamen (CPu) is known to be
      activated by stimulation of supersensitive D1 receptors. Immunohistochemical
      studies on c-fos revealed sparse c-fos positive nuclei in the lesioned CPu after
      1.5 mg/kg of SKF 38393, whereas after combined administration of (+)MK-801 and
      SKF 38393, dense labeling of nuclei was obtained in the dorso-lateral aspect of
      the CPu. Therefore, blockade of NMDA receptors acts synergistically with D1 and
      antagonistically with D2 receptor stimulation in the 6-OHDA model of turning,
      suggesting that different neuronal pathways are involved in the mediation of D1
      and D2 responses.

PMID- 1346166
TI  - The insulin-secreting cell line, RINm5F, expresses an alpha-2D adrenoceptor and
      nonadrenergic idazoxan-binding sites.
AB  - The pharmacological properties of alpha-2 adrenoceptors and the existence of
      nonadrenergic idazoxan-binding sites (NAIBS) were investigated in the insulin
      secreting cell-line, RINm5F, using [3H]RX821002 and [3H]idazoxan. Analysis of
      [3H]RX821002 saturation isotherms revealed the presence of a single class of
      binding sites (Bmax = 47.5 +/- 3.5 fmol/mg protein) having high affinity (Kd =
      1.26 +/- 0.18 nM). Inhibition of [3H]RX821002 binding by adrenergic compounds
      showed that the labeled sites displayed the properties expected for an alpha-2
      adrenoceptor. Based on competition data with drugs having alpha-2 adrenoceptor
      subtype selectivity, the receptor from RINm5F is neither an alpha-2B nor an alpha
      2C. It resembles the alpha-2A, but deviates from this subtype because of a weak
      affinity for yohimbine and rauwolscine. In this respect, RINm5F alpha-2
      adrenoceptor is identical to the receptor previously described in rat intestinal
      mucosa and corresponds to a fourth subtype: alpha-2D. Agonist inhibition curves
      were better fitted by a two-site model and indicated that about half of the
      receptor population was under a high-affinity state corresponding to G protein
      coupled receptors. [32P]ADP-ribosylation with pertussis toxin and immunodetection
      with specific antibodies permitted the identification of three distinct G
      proteins: Gi2, Gi3 and G0. Binding experiments with [3H]idazoxan showed that this
      imidazoline labeled two types of sites corresponding to alpha-2 adrenoceptors and
      NAIBS. Analysis of saturation isotherms under binding conditions allowing to
      discriminate between the two site populations indicated that the density of NAIBS
      (44 +/- 2 fmol/mg protein) was fairly identical to that of alpha-2 adrenoceptors.
      The pharmacological properties of NAIBS, as assessed by determining the relative
      affinity of imidazolinic and nonimidazolinic compounds, reasonably matched that
      reported in other tissues. Taken together, these data make the RINm5F cell-line
      1) the first model in permanent culture known as expressing an alpha-2
      adrenoceptor of the alpha-2D subtype; 2) a good system for studying in vitro the
      respective role of alpha-2 adrenoceptors and NAIBS in the regulation of insulin
      secretion by beta cells.

PMID- 1346167
TI  - Electrophysiological actions of the pimobendan metabolite, UD-CG 212 Cl, in
      guinea pig myocardium.
AB  - Pimobendan (UD-CG 115 BS), an inotropic agent and inhibitor of type III
      phosphodiesterase activity, is demethylated in vivo to form UD-CG 212 Cl, which
      is a more potent type III phosphodiesterase inhibitor. This study examined cyclic
      AMP (cAMP)-mediated actions of UD-CG 212 Cl. In guinea pig papillary muscles, UD
      CG 212 Cl increased cAMP and stimulated Ca(++)-dependent slow action potentials
      (APs) in a dose-dependent manner. When compared to previous studies using
      pimobendan, UD-CG 212 Cl was approximately 100-fold more potent. UD-CG 212 Cl had
      no additional effects on slow APs in the presence of a maximal dose of
      isoproterenol (1 microM). Propranolol had little effect on UD-CG 212 Cl-induced
      slow APs. These results, along with previous studies, indicate that slow AP
      induction by UD-CG 212 Cl was cAMP-dependent, and the increase in cAMP levels was
      most likely due to phosphodiesterase inhibition and not beta receptor
      stimulation. Experiments with tetraethylammonium.Cl suggested that UD-CG 212 Cl
      probably did not induce slow APs by blocking K+ channels. In voltage-clamped
      ventricular myocytes UD-CG 212 Cl (100 microM) could stimulate Ca++ current (+21
      +/- 5%) when basal cAMP levels were enhanced with a submaximal dose of
      isoproterenol (10(-9)-10(-8) M). Isoproterenol was not required to observe the
      stimulating effect of UD-CG 212 Cl on Ca++ current in intact, nondialyzed cells
      prepared using the nystatin-perforated patch method. Studies with the
      stereoisomers of UD-CG 212 Cl showed that the D-isomer was more potent than the L
      isomer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346168
TI  - Comparison of mu opioid receptor binding on intact neuroblastoma cells with
      guinea pig brain and neuroblastoma cell membranes.
AB  - To better understand opioid binding parameters found in situ, binding studies
      were conducted to mu-opioid receptors on intact SH-SY5Y neuroblastoma cells and
      compared with binding to SH-SY5Y membrane and guinea pig brain membrane
      preparations. The mu-selective peptide antagonist [3H]D-Phe-Cys-Tyr-D-Trp-Orn-Thr
      Pen-Thr-NH2 (CTOP) was used for the binding studies. The fact that CTOP is an
      antagonist and hydrophilic is important for binding to be achieved using intact
      cells. In intact cells, using a physiological buffer, there appears to be only a
      low affinity "agonist" conformation of the receptor. This is in contrast to
      binding in either brain or SH-SY5Y membranes in Tris buffer, in which high
      affinity agonist binding was prevalent. As expected from the binding profiles,
      pertussis toxin treatment of cells has no effect on binding to intact cells, but
      significantly decreases affinity of agonists to cell membranes. In intact cells,
      binding appears to be to a single site and a single state of the mu receptor.
      Although in membrane preparations inhibition curves are shallow, with slope
      factors less than 1.0 for many agonists, on intact cells agonist inhibition
      curves are very steep, with slope factors slightly greater than 1.0.

PMID- 1346169
TI  - Restriction fragment length polymorphism of polymerase chain reaction products
      from vaccine and wild-type varicella-zoster virus isolates.
AB  - The nucleotide changes that result in two restriction endonuclease polymorphisms
      that differentiate wild-type varicella-zoster virus (VZV) from the vaccine strain
      were determined. Oligonucleotide primers that flank these sites were used to
      amplify the intervening sequences with the polymerase chain reaction to identify
      VZV DNA in clinical isolates. Restriction enzyme digestion of the amplification
      products distinguished vaccine and wild-type genomes from one another. This study
      confirms the feasibility of amplifying VZV sequences so that they may be detected
      in clinical specimens and provides a molecular epidemiological approach to strain
      identification of VZV in vesicular lesions.

PMID- 1346170
TI  - Gastric intramucosal pH as a therapeutic index of tissue oxygenation in
      critically ill patients.
AB  - Falls in gastric intramucosal pH (pHi) are associated with morbidity and
      mortality in patients admitted to intensive-care units (ICU). We tested the
      hypothesis that ICU outcome can be improved by therapy guided by changes in pHi
      and aimed at improving systemic oxygen availability. We studied 260 patients
      admitted to ICUs with APACHE II scores of 15-25. After insertion of a gastric
      tonometer, each patient was randomly assigned to a control or protocol group
      within the admission pHi category (normal = 7.35 or higher; low = below 7.35).
      The control groups were treated according to standard ICU practices. The protocol
      groups received, in addition, treatment to increase systemic oxygen transport or
      to reduce oxygen demand, whenever the pHi fell below 7.35 or by more than 0.10
      units from the previous measurement. The protocol was used, because pHi fell, in
      67 (85%) of the protocol group with normal pHi on admission. There were no
      significant differences between protocol and control groups in demographic
      characteristics, admission blood gases or haemoglobin concentration, number or
      type of organ system failures, or the intensity of ICU care. For patients
      admitted with low pHi, survival was similar in the protocol and control groups
      (37% vs 36%), whereas for those admitted with normal pHi, survival was
      significantly greater in the protocol than in the control group (58% vs 42%; p
      less than 0.01). Therapy guided by pHi measurements improved survival in patients
      whose pHi on admission to ICU was normal. pHi-guided resuscitation may help
      improve outcome in such patients by preventing splanchnic organ hypoxia and the
      development of a systemic oxygen deficit.

PMID- 1346171
TI  - Combined chemotherapy with ABCM versus melphalan for treatment of myelomatosis.
      The Medical Research Council Working Party for Leukaemia in Adults.
AB  - Both melphalan and cyclophosphamide increase life expectancy in patients with
      myelomatosis, but few large randomised studies have compared combination
      chemotherapy regimens with these single agents. In the Vth MRC myelomatosis
      trial, the survival of 314 patients randomised to receive ABCM (adriamycin, BCNU,
      cyclophosphamide, and melphalan) as first-line treatment was significantly longer
      than that of 316 patients given intermittent melphalan (M7) (p = 0.0003). The
      75%, median, and 25% survivals were 7, 24, and 42 months, respectively, with M7
      and 10, 32, and 56 months, respectively, with ABCM. Stable disease with few
      symptoms (plateau) was achieved by 61% of patients given ABCM and 49% of those
      given M7 (p = 0.004). Myelotoxicity was comparable between regimens. Cross-trial
      analysis suggests that M7 is comparable to melphalan and prednisone or melphalan,
      prednisone, and vincristine; that the efficacy of ABCM in the Vth trial and VIth
      MRC trials is comparable; and that ABCM gave better survival than intermittent
      melphalan regimens in the prognostic groups analysed. The results indicate that
      ABCM is an acceptable regimen that is more effective than melphalan, with or
      without prednisone, for first-line treatment of myelomatosis.

PMID- 1346172
TI  - Multicentre study of gestrinone in cyclical breast pain.
AB  - Although the aetiology of cyclical mastalgia is poorly understood, the consistent
      finding of an increased prolactin stimulation response probably due to oestrogen
      dominance has led to the use of treatment with prolactin-lowering drugs and
      antioestrogens. The efficacy and safety in cyclical mastalgia of gestrinone,
      which has androgenic, anti-oestrogenic, and antiprogestagenic properties, were
      investigated in a multicentre study. In a double-blind randomisation procedure,
      72 patients were allocated placebo and 73 treatment with gestrinone (2.5 mg twice
      a week) for 3 months. The patients recorded the severity of breast pain on a
      visual analogue scale before and during treatment and scored other breast
      symptoms as not present (0), mild (1), moderate (2), or severe (3). The
      gestrinone group had significantly greater reductions than the placebo group in
      breast pain score at months 1, 2, and 3 of treatment (mean reduction 59.5 [SD
      22.6] to 11.7 [17.0] vs 58.2 [17.6] to 36.7 [23.0] at month 3; p less than
      0.0001). All six breast symptoms had lower scores in the gestrinone than in the
      placebo group by the end of treatment. In a subset of 30 participants (15 from
      each group), serum concentrations of oestradiol, progesterone, and tri
      iodothyronine were significantly lower than baseline after 3 months of
      gestrinone, but concentrations of luteinising hormone, follicle-stimulating
      hormone, prolactin, thyroid-stimulating hormone, and thyroxine did not change.
      41% of gestrinone-treated and 14% of placebo-treated patients reported at least
      one side-effect; most of these were androgen-mediated. 11 placebo-treated
      patients and 4 on gestrinone discontinued treatment. Thus, gestrinone was very
      effective in the treatment of cyclical mastalgia and was well tolerated.

PMID- 1346173
TI  - Cassava cyanogens and konzo, an upper motoneuron disease found in Africa.
AB  - Konzo is a distinct form of tropical myelopathy characterised by abrupt onset of
      spastic paraparesis. Epidemics in East Africa have been attributed to dietary
      cyanide exposure from insufficiently processed cassava but a study done in Zaire
      disputed such an aetiology. We investigated a konzo-affected population in rural
      Zaire and measured the cyanogen content of cassava flour, determined urinary
      thiocyanate as an indicator of cyanide intake, and compared blood cyanide
      concentrations in cases and controls. The affected population consumed flour made
      from short-soaked (one day) cassava roots and thus had high dietary cyanide
      exposure (urinary thiocyanate in 31 children = 757 mumol/l) compared with the
      unaffected population (urinary thiocyanate in 46 children = 50 mumol/l) that ate
      cassava that had been soaked for three days before consumption. 3 konzo patients,
      but only 2 of 23 controls, had blood cyanide concentrations above 4 mumol/l (p
      less than 0.01), although serum thiocyanate concentrations were similar. Our
      findings indicate a causal role in konzo of sustained high blood cyanide
      concentrations maintained by a deficient sulphur intake impairing cyanide to
      thiocyanate conversion. The underlying causes of konzo are poverty and food
      shortage, but a minor improvement of food processing may, as in beri-beri, be
      preventive.

PMID- 1346174
TI  - Ventricular arrhythmias and four-year mortality in haemodialysis patients. Gruppo
      Emodialisi e Patologie Cardiovascolari.
AB  - 127 randomly selected patients on haemodialysis showed a high prevalence of
      ventricular arrhythmias, the frequency of which rose significantly during and
      after dialysis. These patients have now been followed up for 4 years. Only age
      and ischaemic heart disease correlated independently with mortality. Although
      ventricular arrhythmias are often associated with cardiac disease in patients on
      chronic haemodialysis, they do not seem to predict overall mortality.

PMID- 1346176
TI  - Single lung transplantation for pulmonary emphysema.

PMID- 1346175
TI  - Control of scarring in adult wounds by neutralising antibody to transforming
      growth factor beta.
AB  - Adult wounds heal with scar-tissue formation, whereas fetal wounds heal without
      scarring and with a lesser inflammatory and cytokine response. We injected the
      margins of healing dermal wounds in adult rats with neutralising antibody (NA) to
      transforming growth factor-beta (TGF-beta). All control wounds (irrelevant
      antibody, or TGF-beta, or no injection) healed with scarring, whereas the NA
      treated wounds healed without scar-tissue formation; NA-treated wounds had fewer
      macrophages and blood vessels, lower collagen and fibronectin contents, but
      identical tensile strength and more normal dermal architecture than the other
      wounds. Early manipulation of the concentrations of selected cytokines may be a
      new approach to the control of scarring.

PMID- 1346177
TI  - Pot-scourer pleurodesis for pneumothorax.

PMID- 1346178
TI  - Anismus and biofeedback.

PMID- 1346179
TI  - Neural tube closure retains its secrets.

PMID- 1346180
TI  - Cereal-based oral rehydration solutions--bridging the gap between fluid and food.

PMID- 1346181
TI  - Acute pressure area care: Sir James Paget's legacy.

PMID- 1346182
TI  - Randomised controlled trial of day care for hypertension in pregnancy.
AB  - Our aim was to assess the effect of the introduction of a day-care unit on the
      care of women with non-proteinuric hypertension in pregnancy. A randomised
      controlled trial was carried out on 54 women who presented at 26 weeks of
      pregnancy or later with non-proteinuric hypertension (systolic blood pressure 150
      170 mm Hg and/or diastolic pressure 90-105 mm Hg on two occasions at least 15 min
      apart). 30 women were allocated to care by the day unit and 24 were managed
      according to the established practice of their clinicians without access to the
      day unit (control group). Women in the control group spent on average 4.6 times
      longer as inpatients (difference in mean stay 4.0 days [95% confidence interval
      2.1-5.9 days]) than the day-unit group and were 8.8 times (95% CI 3.0-25.8) more
      likely to be admitted to hospital. Induction of labour was 4.9 times (95% CI 1.6
      13.8) more likely in the control than in the day-unit group and the development
      of proteinuria 11.4 times (95% CI 1.8-71.4) more likely. The control group had a
      mean of 1.5 fewer hospital outpatient visits (95% CI 0.36-2.64). The groups did
      not differ in their use of antihypertensive drugs. Day-unit care for hypertension
      in pregnancy significantly reduced the need for and the length of antenatal
      inpatient admissions and the number of medical interventions, at the cost of an
      increase in outpatient attendances. Our results are further evidence that
      inpatient care does not improve outcomes or prevent the development of
      proteinuria in this disorder.

PMID- 1346184
TI  - Funding research and development in the NHS.

PMID- 1346183
TI  - Contraceptive efficacy of lactational amenorrhoea.
AB  - Pregnancy is rare among breastfeeding women with lactational amenorrhoea. The
      lactational amenorrhoea method (LAM) is the informed use of breastfeeding as a
      contraceptive method by a woman who is still amenorrhoeic, and who is not feeding
      her baby with supplements, for up to 6 months after delivery. Under these three
      conditions, LAM users are thought to have 98% protection from pregnancy. It can
      be difficult, however, to determine when supplementation of the baby's diet
      begins. We have analysed data from nine studies of the recovery of fertility in
      breastfeeding women to assess the effectiveness of lactational amenorrhoea alone,
      irrespective of whether supplements have been introduced, as a fertility
      regulation method post partum. Cumulative probabilities of ovulation during
      lactational amenorrhoea were 30.9 and 67.3 per 100 women at 6 and 12 months,
      respectively, compared with 27.2 at 6 months when all three criteria of the LAM
      were met. Cumulative pregnancy rates during lactational amenorrhoea were 2.9 and
      5.9 per 100 women at 6 and 12 months, compared with 0.7 at 6 months for the LAM.
      The probability of pregnancy during lactational amenorrhoea calculated from these
      studies is similar to that of other modern contraceptive methods, and it seems
      reasonable for a woman to rely on lactational amenorrhoea without regard to
      whether she is fully or partly breastfeeding. So that amenorrhoea and fertility
      suppression can be maintained, counselling about good breastfeeding and weaning
      practices remains important.

PMID- 1346185
TI  - Science and the Dingell factor.

PMID- 1346186
TI  - Keyboard operators' repetitive strain injury.

PMID- 1346187
TI  - AIDS in Africa.

PMID- 1346188
TI  - Trial by myth.

PMID- 1346189
TI  - Necrotising enterocolitis--a community-acquired infectious disease?

PMID- 1346190
TI  - Sunbathing and gallstones.

PMID- 1346191
TI  - Culprit coronary artery lesion.

PMID- 1346192
TI  - IgA antibodies to endomysium, gliadin, and reticulin in silent coeliac disease.

PMID- 1346193
TI  - Heart failure and octreotide in acromegaly.

PMID- 1346194
TI  - Trans-sensing hypothesis for origin of Beckwith-Wiedemann syndrome.

PMID- 1346195
TI  - Molecular cytogenetics of Prader-Willi and Angelman syndromes.

PMID- 1346196
TI  - Management of uveitis.

PMID- 1346197
TI  - Prevalence of end-stage renal failure and severe retinopathy in type 2 diabetes.

PMID- 1346198
TI  - Amyloid beta-protein deposition in skin of patients with dementia.

PMID- 1346200
TI  - Transmission of HIV-1 infection after a fight.

PMID- 1346199
TI  - Intrauterine and intrapartum transmission of HIV.

PMID- 1346201
TI  - Celiprolol.

PMID- 1346203
TI  - Disintegration of Yugoslavia.

PMID- 1346202
TI  - Treatment of CMV retinitis.

PMID- 1346204
TI  - Medical information.

PMID- 1346205
TI  - Medical information.

PMID- 1346206
TI  - Academic cardiology at Hammersmith Hospital.

PMID- 1346207
TI  - Academic cardiology at Hammersmith Hospital.

PMID- 1346208
TI  - Sick building syndrome and sinusitis.

PMID- 1346209
TI  - Undergraduate teaching on chronic wound care.

PMID- 1346210
TI  - Diet therapy in rheumatoid arthritis.

PMID- 1346212
TI  - Platelet size and venous disease.

PMID- 1346211
TI  - Patient referral and NHS reforms.

PMID- 1346213
TI  - Electronic diary to record physiological measurements.

PMID- 1346214
TI  - Managing hypertension in the elderly.

PMID- 1346215
TI  - Managing hypertension in the elderly.

PMID- 1346216
TI  - Childhood leukaemia on Greek islands.

PMID- 1346217
TI  - Catamenial epilepsy and goserelin.

PMID- 1346218
TI  - Fashions in breastfeeding.

PMID- 1346219
TI  - Post-transfusion fulminant hepatitis B after screening for hepatitis B virus core
      antibody.

PMID- 1346220
TI  - Chirality of penicillamine.

PMID- 1346221
TI  - Cyclosporin and muscle.

PMID- 1346222
TI  - Two types of translucent membrane of caesarean section scar tissue.

PMID- 1346223
TI  - Long QT and Harvey-ras.

PMID- 1346224
TI  - Safety of fluconazole in women taking oral hypoglycaemic agents.

PMID- 1346225
TI  - Malignant hyperthermia and Hirschsprung's disease.

PMID- 1346226
TI  - Postpartum idiopathic polymyositis.

PMID- 1346227
TI  - Renal effects of dopamine and dopexamine in the newborn anesthetized rabbit.
AB  - The renal effects of dopexamine, a new dopaminergic agonist with marked beta 2
      adrenergic agonist properties, but no alpha-adrenergic effect, has been studied
      in 8 newborn New Zealand rabbits, whose renal functional characteristics show
      close similarities with those of premature infants. Six animals were used as
      controls. After a control period, dopexamine was infused intravenously at a rate
      of 4 micrograms/kg per min and after a wash-out period, at 10 micrograms/kg per
      min. The renal effects of dopamine were studied in similar conditions. Glomerular
      filtration rate (GFR) and renal plasma flow (RPF) were determined by inulin and
      para-aminohippuric acid clearances, respectively. Dopexamine, 4 micrograms/kg per
      min, did not induce changes in cardiovascular and renal hemodynamics or in renal
      functions. At 10 micrograms/kg per min, a significant increase in urine flow rate
      (25 +/- 5%; p less than 0.01), urine sodium excretion (77 +/- 17%; p less than
      0.01) and fractional sodium excretion (69 +/- 25%; p less than 0.05) was
      observed. The GFR, RPF and renal vascular resistance (RVR) were not affected.
      Heart rate increased slightly but significantly (8 +/- 3%; p less than 0.05),
      without change in mean blood pressure (MBP). Dopamine, 4 micrograms/kg per min,
      decreased slightly albeit significantly MBP (3 +/- 1%; p less than 0.05). At 10
      micrograms/kg per min the only renal effect was a significant increase in RVR (19
      +/- 6%; p less than 0.02). The different actions of these two dopaminergic
      agonists in this immature model could be explained by their respective ability to
      activate electively the adrenergic and dopaminergic peripheral receptors. The
      natriuretic and diuretic effect of dopexamine in normal immature rabbits, in the
      absence of changes in RPF or GFR is probably mediated by a direct action of this
      agent on dopaminergic tubular receptors. Failure of these two drugs to increase
      RPF may be related to an immaturity of the dopaminergic vascular receptors.

PMID- 1346228
TI  - Molecular biology. Extinction by indirect means.

PMID- 1346229
TI  - Postsynaptic contribution to long-term potentiation revealed by the analysis of
      miniature synaptic currents.
AB  - Miniature excitatory synaptic currents were recorded from CA1 pyramidal cells in
      hippocampal slices to study the site of the persistent change in synaptic
      efficacy during long-term potentiation. Induction of long-term potentiation
      produced a large increase in the amplitude of these currents. Such a change in
      amplitude suggests an increase in postsynaptic transmitter sensitivity.

PMID- 1346230
TI  - Activation of a C. elegans Antennapedia homologue in migrating cells controls
      their direction of migration.
AB  - Anterior-posterior patterning in insects, vertebrates and nematodes involves
      members of conserved Antennapedia-class homeobox gene clusters (HOM-C) that are
      thought to give specific body regions their identities. The effects of these
      genes on region-specific body structures have been described extensively,
      particularly in Drosophila, but little is known about how HOM-C genes affect the
      behaviours of cells that migrate into their domains of function. In
      Caenorhabditis elegans, the Antennapedia-like HOM-C gene mab-5 not only specifies
      postembryonic fates of cells in a posterior body region, but also influences the
      migration of mesodermal and neural cells that move through this region. Here we
      show that as one neuroblast migrates into this posterior region, it switches on
      mab-5 gene expression; mab-5 then acts as a developmental switch to control the
      migratory behaviour of the neuroblast descendants. HOM-C genes can therefore not
      only direct region-specific patterns of cell division and differentiation, but
      can also act within migrating cells to programme region-specific migratory
      behaviour.

PMID- 1346231
TI  - Palaeontology. In the Grube in the Eocene.

PMID- 1346232
TI  - The eukaryotic initiation factor 2-associated 67-kDa polypeptide (p67) plays a
      critical role in regulation of protein synthesis initiation in animal cells.
AB  - The eukaryotic initiation factor 2 (eIF-2)-associated 67-kDa polypeptide (p67)
      isolated from reticulocyte lysate protects the eIF-2 alpha subunit from eIF-2
      kinase-catalyzed phosphorylation and promotes protein synthesis in the presence
      of active eIF-2 kinases. We have now studied the roles of p67 and eIF-2 kinases
      in regulation of protein synthesis using several animal cell lysates and an
      animal cell line (KRC-7) in culture under various growth conditions. The results
      are as follows. (i) Both p67 and eIF-2 kinase(s) are present in active forms in
      all animal cells under normal growth conditions and p67 protects the eIF-2 alpha
      subunit from eIF-2 kinase-catalyzed phosphorylation, thus promoting protein
      synthesis in the presence of active eIF-2 kinases. (ii) In heme-deficient
      reticulocyte lysates and in serum-starved KRC-7 cells in culture, p67 is
      deglycosylated and subsequently degraded. This leads to eIF-2 kinase-catalyzed
      eIF-2 alpha-subunit phosphorylation and thus to protein synthesis inhibition.
      (iii) Addition of a mitogen (namely, phorbol 12-myristate 13-acetate) to serum
      starved KRC-7 cells in culture induces an increase of p67 and thus increases
      protein synthesis. These results suggest the following conclusions. (i) Protein
      synthesis inhibition in a heme-deficient reticulocyte lysate is not due to the
      activation of an eIF-2 kinase (heme-regulated inhibitor), as is generally
      believed, but is due to degradation of p67. The heme-regulated inhibitor is
      present in an active form and possibly in equal amounts in both heme-deficient
      and heme-supplemented reticulocyte lysates but cannot phosphorylate eIF-2 alpha
      subunit because of the presence of p67. (ii) p67 is essential for protein
      synthesis as it protects the eIF-2 alpha subunit from eIF-2 kinase-catalyzed
      phosphorylation and promotes protein synthesis in the presence of one or more
      active eIF-2 kinases present in all animal cells. (iii) p67 is both degradable
      and inducible. Only the p67 level correlates directly with the protein synthesis
      activity of the cell, indicating that p67 is a critical factor in protein
      synthesis regulation in animal cells.

PMID- 1346233
TI  - Synaptic localization of kappa opioid receptors in guinea pig neostriatum.
AB  - Distribution of kappa opioid receptors was examined by EM radioautography in
      sections of guinea pig neostriatum with the selective 125I-labeled dynorphin
      analog [D-Pro10]dynorphin-(1-11). Most specifically labeled binding sites were
      found by probability circle analysis to be associated with neuronal membrane
      appositions. Because of limitations in resolution of the method, the radioactive
      sources could not be ascribed directly to either one of the apposed plasma
      membranes. Nevertheless, three lines of evidence favored a predominant
      association of ligand with dendrites of intrinsic striatal neurons: (i) the high
      frequency with which labeled interfaces implicated a dendrite, (ii) the
      enrichment of dendro-dendritic interfaces, and (iii) the occurrence of dendritic
      profiles labeled at several contact points along their plasma membranes. A small
      proportion of labeled sites was associated with axo-axonic interfaces, which may
      subserve the kappa opioid-induced regulation of presynaptic dopamine and
      acetylcholine release documented in guinea pig neostriatum. Although most
      membrane-associated kappa sites were found at extrasynaptic locations,
      approximately 23% were associated with synaptic specializations. This proportion
      is markedly higher than that previously reported for either mu or delta sites in
      rat neostriatum. Whether labeled synapses represent preferential sites of action
      for kappa ligands remains to be established. In any event, these results support
      the hypothesis that in mammalian brain kappa opioid receptors are
      conformationally and functionally distinct from mu and delta types.

PMID- 1346234
TI  - Most gamma delta T cells develop normally in beta 2-microglobulin-deficient mice.
AB  - The specificity of T cells bearing gamma delta T-cell receptors (gamma delta+ T
      cells) is poorly characterized. Earlier studies suggest that like alpha beta+CD8+
      T cells, some gamma delta+ T cells may recognize antigens associated with class I
      major histocompatibility complex molecules. alpha beta+CD8+ T cells are nearly
      absent in class I-deficient mice (mutant for beta 2-microglobulin), reflecting a
      requirement for intrathymic "positive selection" of these cells by class I
      molecules. Here, we examine whether the development of gamma delta+ T cells is
      altered in the beta 2-microglobulin mutant mice. We show that the cellularity,
      marker expression, repertoire, and functional competence of gamma delta+ T cells
      are not detectably deficient in beta 2-microglobulin mutant mice. We conclude
      that class I expression is unnecessary for the development of most gamma delta+ T
      cells.

PMID- 1346235
TI  - Hyperthyroidism due to inappropriate secretion of thyrotropin in 10 patients.
AB  - PURPOSE: The syndrome of inappropriate thyroid-stimulating hormone (TSH)
      secretion, characterized by elevated serum free thyroxine and triiodothyronine
      levels in association with measurable serum TSH concentrations, remains an
      uncommon cause of hyperthyroidism that is being recognized with increasing
      frequency. The hyperthyroidism may be due to either neoplastic pituitary TSH
      secretion or selective pituitary resistance to thyroid hormone. In an effort to
      better understand this rare cause of hyperthyroidism, we undertook a
      retrospective analysis of our institution's experience with this condition.
      PATIENTS: We reviewed our cumulative experience (10 patients) with
      hyperthyroidism due to the syndrome of inappropriate secretion of TSH. RESULTS:
      Six patients were diagnosed with TSH-secreting pituitary adenomas and four were
      found to have selective pituitary resistance to thyroid hormone. One patient with
      tumor had a TSH-secreting pituitary adenoma in the setting of multiple endocrine
      neoplasia syndrome. In all patients with tumor, hyperthyroidism was successfully
      treated with transsphenoidal adenomectomy with or without pituitary radiotherapy.
      All four patients with pituitary resistance had thyroid ablation or resection
      prior to their correct diagnosis. Therefore, therapy for this group of patients
      involved thyroid hormone replacement and efforts to suppress TSH hypersecretion.
      All 10 patients have done well clinically, with follow-up ranging from 2 weeks to
      13 years. CONCLUSIONS: Adequate treatment exists for the two primary causes of
      TSH hypersecretion. TSH-secreting pituitary adenomas are treated with surgery
      and, if necessary, adjuvant pituitary radiotherapy. The results are generally
      good if the tumor is diagnosed and treated at an early stage. Primary therapy for
      hyperthyroidism due to selective pituitary resistance to thyroid hormone is aimed
      at suppression of pituitary TSH hypersecretion. The evaluation of any patient
      with hyperthyroidism must be thorough and, in some cases, should include
      measurement of TSH to determine the presence of inappropriate secretion.
      Eliminating this diagnosis will help avoid improper and potentially harmful
      treatment of hyperthyroid patients.

PMID- 1346236
TI  - Neu proto-oncogene amplification and expression in ovarian adenocarcinoma cell
      lines.
AB  - In this communication, the authors summarize their characterization of eight
      ovarian adenocarcinoma-derived cell lines for level of neu gene amplification,
      expression of neu transcripts and protein, and intraperitoneal tumorigenicity in
      nude mice. Two of the eight cell lines in our study (SKOV3 and YAOVBIX1)
      exhibited five- to ninefold neu DNA sequence amplification, accompanied by up to
      200-fold overexpression of transcripts and protein (p185). Both of these cell
      lines expressed a major approximately 7.5 kb neu-complementary transcript not
      previously reported in other neu-positive tumor cell lines. One pair of cell
      lines (YAOVBIX1 and YAOVBIX3), isolated from a single ovarian carcinoma patient's
      ascites sample differed dramatically in regard to level of neu gene amplification
      and expression. Immunohistochemical staining of the primary ovarian tumor from
      which these two lines were derived demonstrated populations of both neu-positive
      and neu-negative malignant epithelial cells. Seven of the eight ovarian carcinoma
      lines produced intra-abdominal tumors after intraperitoneal injection into nude
      mice, irrespective of level of neu gene expression. This study demonstrates tumor
      cell heterogeneity with regard to neu gene amplification and expression in an
      ovarian adenocarcinoma, reveals the overexpression of novel neu-complementary
      transcripts in two independently isolated ovarian adenocarcinoma cell lines, and
      suggests that neu gene expression is not required for intraperitoneal
      tumorigenicity of ovarian carcinoma xenografts in a nude mouse model system.

PMID- 1346237
TI  - Management of epidural anesthesia in a patient with Takayasu's disease.

PMID- 1346238
TI  - Anesthetic management for the child with Charcot-Marie-Tooth disease.

PMID- 1346239
TI  - International Anesthesia Research Society 66th Congress. San Francisco,
      California, March 13-17, 1992. Abstracts.

PMID- 1346240
TI  - Relative role of the glutaminase, glutamate dehydrogenase, and AMP-deaminase
      pathways in hepatic ureagenesis: studies with 15N.
AB  - We have studied the relative roles of the glutaminase versus glutamate
      dehydrogenase (GLDH) and purine nucleotide cycle (PNC) pathways in furnishing
      ammonia for urea synthesis. Isolated rat hepatocytes were incubated at pH 7.4 and
      37 degrees C in Krebs buffer supplemented with 0.1 mM L-ornithine and 1 mM [2
      15N]glutamine, [5-15N]glutamine, [15N]aspartate, or [15N]glutamate as the sole
      labeled nitrogen source in the presence and absence of 1 mM amino-oxyacetate
      (AOA). A separate series of incubations was carried out in a medium containing
      either 15N-labeled precursor together with an additional 19 unlabeled amino acids
      at concentrations similar to those of rat plasma. GC-MS was utilized to determine
      the precursor product relationship and the flux of 15N-labeled substrate toward
      15NH3, the 6-amino group of adenine nucleotides ([6-15NH2]adenine), 15N-amino
      acids, and [15N]urea. Following 40 min incubation with [15N]aspartate the
      isotopic enrichment of singly and doubly labeled urea was 70 and 20 atom %
      excess, respectively; with [15N]glutamate these values were approximately 65 and
      approximately 30 atom % excess for singly and doubly labeled urea, respectively.
      In experiments with [15N]aspartate as a sole substrate 15NH3 enrichment exceeded
      that in [6-NH2]adenine, indicating that [6-15NH2]adenine could not be a major
      precursor to 15NH3. Addition of AOA inhibited the formation of [15N]glutamate,
      15NH3 and doubly labeled urea from [15N]aspartate. However, AOA had little effect
      on [6-15NH2]adenine production. In experiments with [15N]glutamate, AOA inhibited
      the formation of [15N]aspartate and doubly labeled urea, whereas 15NH3 formation
      was increased. In the presence of a physiologic amino acid mixture,
      [15N]glutamate contributed less than 5% to urea-N. In contrast, the amide and the
      amino nitrogen of glutamine contributed approximately 65% of total urea-N
      regardless of the incubation medium. The current data indicate that when
      glutamate is a sole substrate the flux through GLDH is more prominent in
      furnishing NH3 for urea synthesis than the flux through the PNC. However, in
      experiments with medium containing a mixture of amino acids utilized by the rat
      liver in vivo, the fraction of NH3 derived via GLDH or PNC was negligible
      compared with the amount of ammonia derived via the glutaminase pathway.
      Therefore, the current data suggest that ammonia derived from 5-N of glutamine
      via glutaminase is the major source of nitrogen for hepatic urea-genesis.

PMID- 1346241
TI  - Isolation of two novel sialyl-Lewis X-active oligosaccharides by high-performance
      liquid affinity chromatography using monoclonal antibody Onc-M26.
AB  - A monoclonal antibody, Onc-M26, that recognizes a cancer-associated antigen
      expressed by most human adenocarcinomas of the breast was shown previously to
      recognize a carbohydrate epitope carried on a hexaglycosyl ganglioside carrying
      the sialyl-Lewis X (SLex) antigen (P.S. Linsley et al., 1988, Cancer Res. 48,
      2138-2148). Evidence that the antibody binds even more avidly to minor
      gangliosides containing more complex carbohydrate chains prompted us to search
      for a higher affinity epitope among sialylated oligosaccharides from pooled human
      milk. Affinity chromatography of a partially purified fraction of monosialylated
      milk oligosaccharides on a column containing monoclonal antibody Onc-M26 bound to
      a macroporous silica matrix gave a peak with a retention volume significantly
      greater than that of a standard SLex-active hexasaccharide. The retained material
      consisted of two nonasaccharides, each containing the SLex tetrasaccharide
      sequence, Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3) GlcNAc, linked beta 1-6 to
      a 3,6-disubstituted galactosyl residue.

PMID- 1346242
TI  - Changing profiles of failed coronary angioplasty patients: impact on surgical
      results.
AB  - As more high-risk patients undergo percutaneous transluminal coronary angioplasty
      (PTCA), the changing profiles of PTCA patients who may require emergent coronary
      artery bypass grafting may alter operative morbidity and mortality. This study
      compared profiles of recent patients undergoing emergent coronary artery bypass
      grafting after a failed PTCA with earlier patients to determine their impact on
      operative results. From 1980 to 1988, 53 patients underwent emergent coronary
      artery bypass grafting after a failed PTCA at the Boston University Medical
      Center. These patients were divided into two groups based on the year of the
      PTCA: group I, 1980 to 1985 (n = 18); and group II, 1986 to 1988 (n = 35). Group
      II patients tended to be older (age greater than or equal to 65 years, 47% group
      II versus 11% group I), were more likely to have unstable angina before PTCA (74%
      versus 33%), and had lower ejection fractions (0.53 +/- 0.02 versus 0.63 +/-
      0.05) and more vessels with 50% or greater stenosis (2.1 +/- 0.2 versus 1.6 +/-
      0.2). Nevertheless, there was no significant difference in the incidence of
      perioperative myocardial infarcts using enzyme and electrocardiographic criteria
      (37% in group II versus 39% in group I), 30-day operative mortality (11% in group
      II versus 11% in group I), or major postoperative complications (14% in group II
      versus 22% in group I). We conclude that despite the changing profiles of
      patients undergoing PTCA, which include older patients with more extensive
      coronary artery disease and lower ejection fractions, operative results after
      emergent coronary artery bypass grafting for failed PTCAs remain unchanged.

PMID- 1346243
TI  - A novel variant of Sindbis virus is both neurovirulent and neuroinvasive in adult
      mice.
AB  - A strain of Sindbis virus (SV), recently isolated from mosquitoes in Israel, was
      used as a source for variants which differ in neuroinvasiveness and virulence
      that were generated by serial passage of SV in suckling and weanling mouse brain.
      At the 15th passage a neurovirulent variant was observed and designated SVN
      (neurovirulent). After 7 more passages in weanling mouse brains, another variant
      was observed and designated SVNI (neuroinvasive) and both were isolated and
      purified. All strains caused similar viremia after intraperitoneal (I.P.)
      injection of weanling mice, but whereas SV was neuroinvasive but nonvirulent, SVN
      was neurovirulent but noninvasive and SVNI was both virulent and invasive. SVNI
      is the first SV variant which is both neurovirulent and neuroinvasive in weanling
      mice. Co-injection I.P. of SV + SVN resulted in presence of SV alone in the mouse
      brain; co-injection of SVNI + SVN resulted in full-titered replication of both
      strains in the brain. We assume that this is achieved through a breach of the
      blood brain barrier effected by SVNI replication and used by SVN for co-invasion.
      SV probably invades the brain by a different mechanism. I.P. infection with SVNI
      of inbred BALB/c mice gave rise to clinical signs only in a few mice even though
      substantial viremia was demonstrated.

PMID- 1346244
TI  - A cDNA construct of tissue inhibitor of metalloproteinases (TIMP) linked to the
      last exon of Thy-1 confers glycophospholipid anchorage on this naturally secreted
      protein.
AB  - A naturally secreted protein, tissue inhibitor of metalloproteinases (TIMP), has
      been transiently expressed on the surface of transfected COS cells and stably on
      transfected murine BW 5147 thymoma cells, by linkage of the entire coding
      sequence of the cDNA to the last exon of Thy-1. Thy-1 is a glycophospholipid
      linked protein. In COS cells the chimaeric protein can be labelled by
      [3H]ethanolamine, which is a component of glycophospholipid anchors. Ltk- cells
      cannot anchor proteins by glycan phosphatidylinositol linkage and were found to
      be unable to express the engineered protein extracellularly on their plasma
      membranes. Phosphatidylinositol-specific phospholipase C treatment released 90%
      of the protein from all BW 5147 cells, but very little from the COS-1 cells. It
      is concluded that the last exon of Thy-1 has conferred the property of
      glycophospholipid anchorage on the normally secreted protein TIMP.

PMID- 1346245
TI  - Induction of peroxisomal beta-oxidation genes by retinoic acid in cultured rat
      hepatocytes.
AB  - Retinoic acid is reported here to induce peroxisomal beta-oxidation activities in
      cultured rat hepatocytes, with a concomitant increase in respective peroxisomal
      mRNAs. The concentrations of retinoic acid required for inducing liver
      peroxisomal acyl-CoA oxidase were similar to those required for inducing liver
      transglutaminase. A putative 5'-flanking response element for retinoic acid may
      be found within the enhancer region involved in the induction of peroxisomal
      genes by xenobiotic amphipathic carboxylates.

PMID- 1346246
TI  - Differential expression of two msh-related homeobox genes Chox-7 and Chox-8
      during chick limb development.
AB  - We have isolated two closely related cDNAs, Chox-7 and Chox-8, encoding
      homeodomain-containing proteins homologous to Drosophila msh. The Chox-7 and Chox
      8 genes are chicken cognates of mouse Hox-7.1 and Hox-8.1, respectively. In situ
      hybridization using 3' regions of the cDNAs as probes revealed that the Chox-7
      gene is highly expressed in the mesenchyme subjacent to the apical ectodermal
      ridge whereas Chox-8 expression is localized in the anterodistal mesenchymal
      region at early stages of limb formation, suggesting different roles during limb
      development. At later stages, both genes are expressed in the anterior and
      posterior mesenchymes and in the interdigital mesenchyme where programmed cell
      death occurs.

PMID- 1346247
TI  - High-density lipoprotein antagonizes the inhibitory effects of oxidized low
      density lipoprotein and lysolecithin on soluble guanylyl cyclase.
AB  - Oxidatively modified LDL (LDLox) reduces the response of soluble guanylyl cyclase
      to nitrovasodilators. We now demonstrate that this desensitization can be
      antagonized by HDL. Similar to its protective effect against LDLox, HDL also
      inhibited the lysolecithin-induced desensitization of soluble guanylyl cyclase.
      Since the lysolecithin content of LDLox correlated with the amount of
      lysolecithin necessary to diminish stimulation of soluble guanylyl cyclase, our
      data support the hypothesis that lysolecithin may be responsible for the
      inhibitory effect of LDLox on smooth muscle relaxation and provide evidence that
      the antagonistic effect of HDL against desensitization of soluble guanylyl
      cyclase by atherogenic compounds could be responsible for the protective role of
      HDL in atherosclerosis.

PMID- 1346248
TI  - Structure of the mouse tyrosine hydroxylase gene.
AB  - The mouse tyrosine hydroxylase (TH) gene was isolated from a genomic library by
      cross-hybridization with human TH cDNA probe. Nucleotide sequence analysis of two
      overlapping genomic clones showed that this gene is split into 13 exons
      distributed about 7.5 kb in length. The transcription initiation site was
      determined by primer extension analysis with mouse adrenal gland poly(A)+RNA. The
      structure of the mouse TH gene was similar to that of the human TH gene, but it
      contained neither the alternative splice donor site around the 3'-end of the
      first exon nor an independent exon corresponding to the second exon of the human
      TH gene. There were the canonical TATA and GC boxes, cyclic AMP responsive
      element (CRE), and AP1 binding site in the 5'-flanking region of the mouse TH
      gene.

PMID- 1346249
TI  - Liver enzyme levels in arthritis patients treated with long-term bolus
      methotrexate.

PMID- 1346250
TI  - Lipoproteins and their genetic variation in subjects with and without
      angiographically verified coronary artery disease.
AB  - To examine the concentration of serum lipoproteins and the association of their
      genetic variation with the occurrence of coronary artery disease (CAD), composite
      serum lipoprotein profiles including lipoprotein(a) (Lp[a]), apolipoprotein (apo)
      E phenotypes, and apo B Xba I genotypes were determined in patients with
      angiographically verified CAD (CAD+ group, n = 111) and in subjects with no
      angiographic evidence of CAD (CAD- group, n = 46). In addition, we determined the
      concentrations of serum lipids, lipoproteins, and apolipoproteins in 96 healthy
      controls. Both CAD- and CAD+ groups had lower concentrations of apos A-I and A-II
      but higher concentrations of serum total and very low density lipoprotein
      triglyceride and very low density lipoprotein cholesterol than did healthy
      controls. The mean concentrations of serum total and low density lipoprotein
      cholesterol and the median values of Lp(a) were similar in the CAD+ and CAD-
      groups, both having higher concentrations of low density lipoprotein cholesterol
      and apo B than the healthy controls. Irrespective of gender, patients with CAD
      had significantly lower serum high density lipoprotein cholesterol than did those
      without CAD (1.48 +/- 0.40 versus 1.16 +/- 0.29 mmol/l, p less than 0.001). In
      women, the mean serum total and very low density lipoprotein triglyceride
      concentration was also higher in the CAD+ than in the CAD- group. The frequency
      of the apo E4 allele (epsilon 4) was significantly higher in the CAD+ group
      (0.293) than in the CAD- group (0.174; p less than 0.001). The frequencies of the
      two apo B alleles, X1 (Xba I restriction site absent) and X2 (Xba I restriction
      site present), were similar in the two groups. Stepwise discriminant analysis
      revealed that in men, serum high density lipoprotein cholesterol had the highest
      power to discriminate for CAD. In addition, the concentration of plasma apo B
      levels and the occurrence of apo E phenotypes were independently associated with
      CAD in men. In women, the only independent factor associated with CAD after
      adjustment for beta-blocker and diuretics usage was the concentration of serum
      triglycerides.

PMID- 1346251
TI  - Heat shock protein synthesis of the cyanobacterium Synechocystis PCC 6803:
      purification of the GroEL-related chaperonin.
AB  - Synechocystis PCC 6803 cells could be induced to synthesize four major HSPs with
      apparent molecular sizes of 70, 64, 15 and 14 kDa. Heat stress at 42.5 degrees C
      appeared to be the optimum temperature for HSP formation in cells grown at 30
      degrees C. The relative rate of synthesis of HSP70 and HSP15 reached a maximum at
      30 min after the temperature shift-up whereas the capability of cells to
      accumulate HSP64 and HSP14 continued through 2 h. The two most abundant HSPs,
      HSP70 and HSP64, were recognized on western blots by antibodies raised against
      authentic DnaK and GroEL from Escherichia coli. To furnish sufficient evidence
      for the assumption that HSP64 is a GroEL-related chaperonin, this protein was
      purified to homogeneity. There was a 76% sequence identity between the amino acid
      sequence of HSP64 and the corresponding protein in Synechococcus PCC 7942.
      Moreover, the purified HSP64 cross-reacted to anti-E. coli GroEL antibody. To our
      knowledge, this is the first report about the purification and partial protein
      sequencing of a cyanobacterial chaperonin.

PMID- 1346252
TI  - Identification and sequence analysis of the promoter for the leukocyte integrin
      beta-subunit (CD18): a retinoic acid-inducible gene.
AB  - Leukocyte adhesion receptors (LFA-1; Mac-1; p150,95) are a family of
      heterodimeric cell-surface adhesion molecules expressed exclusively in
      granulocytes, lymphocytes, and macrophages. Expression of these proteins is under
      complex regulatory control, but to date promoters for these genes have not been
      identified. The CD18 gene codes for the common beta-subunit of the leukocyte
      adhesion receptors. Transcription of CD18 is highly tissue-specific, hormonally
      inducible (by retinoic acid [RA]), and coordinately regulated with leukocyte
      integrin alpha-chains. To identify the CD18 promoter, we screened a human genomic
      phage library with a human CD18 cDNA probe and obtained a clone that contains an
      exon coding for the 5' untranslated region (UTR). Using rapid amplification of
      cDNA ends (RACE), RNAse protection, S1 nuclease, and primer extension assays, we
      demonstrated the existence of multiple transcription start sites clustered in a
      45-nt region. We investigated the transcription-promoting activity of the genomic
      sequences 5' to the CD18 gene by performing transient expression assays with a
      growth hormone reporter gene in various hematopoietic cell lines. The CD18
      promoter was active in Jurkat cells, a lineage that normally expresses CD18 but
      was considerably less active in K562, an early erythroid line that does not
      normally express CD18. The genomic sequences upstream of the start site cluster
      lack CAAT and TATA boxes, but have two Sp1 binding sites and 10 T(G/C)AC(C/A)
      boxes, which may represent binding sites for RA receptors (RAR). These features
      distinguish the CD18 promoter from the promoters of other tissue-specific,
      hormone-inducible genes, and may be representative of leukocyte integrin
      promoters in general.

PMID- 1346253
TI  - DNA sequence variation in a negative control region 5' to the beta-globin gene
      correlates with the phenotypic expression of the beta s mutation.
AB  - The clinical diversity of sickle cell anemia is strongly related to the degree of
      intracellular hemoglobin S (Hb S) polymerization, which in turn is dependent on
      the intracellular concentration of Hb S. We have recently defined a region of DNA
      approximately 500 bp 5' to the human beta-globin gene that acts as a silencer for
      the transcription of this gene and have shown that a polymorphism in this
      sequence is associated with a thalassemic phenotype of the beta-globin gene. In
      this work we have examined the correlation of DNA sequence polymorphisms in this
      silencer with binding of a previously identified putative repressor protein, BP1,
      and with the expression of Hb S in individuals heterozygous for the beta s
      allele. It was found that specific configurations of the motif, (AT)x(T)y, are
      homogeneous for the major haplotypes of the beta-globin gene cluster described on
      beta s chromosomes. Binding of BP1 was measured to DNA of three haplotypes:
      Indian, Benin, and Bantu. BP1 binds most tightly to DNA of the Indian haplotype,
      and these patients produce less beta s protein than Benin patients, whose DNA
      exhibits weaker affinity for BP1. Binding of BP1 is the weakest to DNA of the
      Bantu haplotype, which is associated with clinically more severe sickle cell
      symptoms. These data are consistent with the hypothesis that these polymorphisms
      may not be neutral and that the DNA sequence at this site may affect the
      expression of the beta s gene. Such an effect may be synergistic with other
      genetic variables, such as fetal hemoglobin levels, F-cell numbers, and the
      number of alpha-globin genes, in determining intracellular polymerization and,
      thus, the severity of the sickle cell syndromes.

PMID- 1346254
TI  - Control of pain.
AB  - Pain in critically ill and injured pediatric patients may go unrecognized and
      undertreated since children often suffer silently and caretakers are often
      fearful to intervene aggressively to alleviate pain. Methods are now readily
      available to relieve pain in the vast majority of ICU patients. Administration of
      inadequate doses of opioids at infrequent intervals or via a noxious route
      (intramuscularly) can be supplanted by far superior pain management methods.
      Provision of nearly constant therapeutic levels of opioid via a painless route is
      recommended and will usually be well tolerated even by very sick children. This
      can be achieved by the use of continuous intravenous infusions of opioids, PCA,
      or epidural administration of local anesthetics or opioids. Flexibility is
      essential so that the appropriate technique or agent can be selected for a
      particular pediatric ICU patient.

PMID- 1346255
TI  - p53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human
      astrocytoma progression.
AB  - The human brain tumor, astrocytoma, typically progresses through three
      histopathologically defined stages with the passage of time: one premalignant
      stage, low-grade astrocytoma; and two malignant stages, anaplastic astrocytoma
      and glioblastoma multiforme. We correlated the results of a sequence analysis of
      the tumor suppressor gene, p53, and a restriction fragment length polymorphism
      analysis of chromosomes 17 and 10 in 45 patients with cerebral astrocytomas at
      different stages. To detect p53 mutations in tumor DNA, we analyzed polymerase
      chain reaction products corresponding to every p53-coding exon for single-strand
      conformation polymorphisms and confirmed the mutations by sequencing. Loss of
      heterozygosity (LOH) was determined by Southern transfer analysis of somatic and
      tumor DNA from these same patients using polymorphic markers for various loci on
      chromosomes 10 and 17. p53 mutations were found in 7 of 25 glioblastomas (28%),
      in 5 of 14 anaplastic astrocytomas (36%) but in 0 of 6 low-grade astrocytomas.
      p53 mutations were found in 62% of patients with LOH on chromosome 17p. These
      results indicated that p53 inactivation is a common genetic event in astrocytoma
      progression that may signal the transition from benign to malignant tumor stages.
      LOH on chromosome 10 was found in 61% of glioblastomas, in 23% of anaplastic
      astrocytomas, but in 0% of low-grade astrocytomas. LOH on chromosome 10 and p53
      mutation were found together only in patients with glioblastoma multiforme (22%),
      suggesting that these genetic changes may accumulate during astrocytoma
      progression.

PMID- 1346256
TI  - Loss of heterozygosity affecting the p53, Rb, and mcc/apc tumor suppressor gene
      loci in dysplastic and cancerous ulcerative colitis.
AB  - Allelic deletions of tumor suppressor genes have been observed frequently in a
      variety of human tumors. These losses are believed to contribute to the
      development of human cancer. Three of the most frequently deleted chromosomal
      loci contain the tumor suppressor genes p53, retinoblastoma (Rb), and mcc/apc. In
      order to detect loss of heterozygosity (LOH) within these genes in dysplastic and
      cancerous ulcerative colitis, we used an application of the polymerase chain
      reaction. LOH affecting p53 was observed in 8 of 17 (47%) of heterozygous
      patients, while LOH of Rb and the mcc/apc locus was observed in 9 of 27 (33%) and
      13 of 39 (33%) of heterozygotes, respectively. Among 35 patients heterozygous at
      2 or more loci, LOH of p53, Rb, and/or mcc/apc was observed in 18 (51%). LOH was
      more common in left-sided neoplasms. These data suggest that allelic deletion of
      p53, Rb, mcc, and/or apc is involved in the pathogenesis and/or progression of at
      least a subset of colonic dysplasias and carcinomas occurring in the setting of
      ulcerative colitis.

PMID- 1346257
TI  - Plasmodium falciparum-infected erythrocytes bind ICAM-1 at a site distinct from
      LFA-1, Mac-1, and human rhinovirus.
AB  - The attachment of erythrocytes infected with P. falciparum to human venular
      endothelium is the primary step leading to complications from severe and cerebral
      malaria. Intercellular adhesion molecule-1 (ICAM-1, CD54) has been implicated as
      a cytoadhesion receptor for P. falciparum-infected erythrocytes. Characterization
      of domain deletion, human/murine chimeric ICAM-1 molecules, and amino acid
      substitution mutants localized the primary binding site for parasitized
      erythrocytes to the first amino-terminal immunoglobulin-like domain of ICAM-1.
      The ICAM-1 binding site is distinct from those recognized by LFA-1, Mac-1, and
      the human major-type rhinoviruses. Synthetic peptides encompassing the binding
      site on ICAM-1 inhibited malaria-infected erythrocyte adhesion to ICAM-1-coated
      surfaces with a Ki of 0.1-0.3 mM, whereas the Ki for soluble ICAM-1 is 0.15
      microM. These findings have implications for the therapeutic reversal of malaria
      infected erythrocyte sequestration in the host microvasculature.

PMID- 1346258
TI  - Analysis of the CYP2D6 gene in relation to debrisoquin and desipramine
      hydroxylation in a Swedish population.
AB  - The molecular basis of polymorphic debrisoquin hydroxylation was studied in 223
      Swedish white subjects, 187 extensive metabolizers and 36 poor metabolizers
      phenotyped with debrisoquin and desipramine. Restriction fragment length
      polymorphism (RFLP) analysis of the CYP2D6 gene revealed that 52% of unrelated
      poor metabolizers were homozygous for Xba I 29 kb fragment, and only 8% had two
      mutant alleles detected with RFLP. Allele-specific polymerase chain reaction
      (PCR)-based DNA amplification, however, revealed that all but one of the poor
      metabolizers had two mutant alleles of the CYP2D6A or CYP2D6B type or both.
      Extensive metabolizers who were heterozygous for wild-type and CYP2D6B genes had
      metabolic ratios for debrisoquin and desipramine that were higher than those of
      subjects who were homozygous for the wild-type gene. The 16 + 9 kb Xba I RFLP
      pattern was associated with the poor metabolizer phenotype and CYP2D6B mutations.
      Three extremely rapid metabolizers of debrisoquin had a 44 kb Xba I fragment that
      did not carry either CYP2D6A or CYP2D6B mutations. In conclusion, in the Swedish
      population studied, allele-specific PCR amplification allowed prediction of the
      debrisoquin hydroxylation phenotype with 99% accuracy.

PMID- 1346259
TI  - Southeast Asian mitochondrial DNA analysis reveals genetic continuity of ancient
      mongoloid migrations.
AB  - Human mitochondrial DNAs (mtDNAs) from 153 independent samples encompassing seven
      Asian populations were surveyed for sequence variation using the polymerase chain
      reaction (PCR), restriction endonuclease analysis and oligonucleotide
      hybridization. All Asian populations were found to share two ancient AluI/DdeI
      polymorphisms at nps 10394 and 10397 and to be genetically similar indicating
      that they share a common ancestry. The greatest mtDNA diversity and the highest
      frequency of mtDNAs with HpaI/HincII morph 1 were observed in the Vietnamese
      suggesting a Southern Mongoloid origin of Asians. Remnants of the founding
      populations of Papua New Guinea (PNG) were found in Malaysia, and a marked
      frequency cline for the COII/tRNA(Lys) intergenic deletion was observed along
      coastal Asia. Phylogenetic analysis indicates that both insertion and deletion
      mutations in the COII/tRNA(Lys) region have occurred more than once.

PMID- 1346260
TI  - Native American mitochondrial DNA analysis indicates that the Amerind and the
      Nadene populations were founded by two independent migrations.
AB  - Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind
      speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence
      variation by detailed restriction analysis. All Native American mtDNAs clustered
      into one of four distinct lineages, defined by the restriction site variants:
      HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp)
      COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np
      13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were
      shared by all such tribal groups analyzed, thus demonstrating that North, Central
      and South American Amerinds originated from a common ancestral genetic stock. The
      9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and
      Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an
      RsaI site loss at np 16,329. The amount of sequence variation accumulated in the
      Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind
      portion of the HaeIII np 663 lineage all gave divergence times in the order of
      20,000 years before present. The divergence time for the Nadene portion of the
      HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene
      migrated from Asia independently and considerably more recently than the
      progenitors of the Amerinds. The divergence times of both the Amerind and Nadene
      branches of the COII-tRNA(Lys) deletion lineage were intermediate between the
      Amerind and Nadene specific lineages, raising the possibility of a third source
      of mtDNA in American Indians.

PMID- 1346261
TI  - A restriction fragment length polymorphism map and electrophoretic karyotype of
      the fungal maize pathogen Cochliobolus heterostrophus.
AB  - A restriction fragment length polymorphism (RFLP) map has been constructed of the
      nuclear genome of the plant pathogenic ascomycete Cochliobolus heterostrophus.
      The segregation of 128 RFLP and 4 phenotypic markers was analyzed among 91 random
      progeny of a single cross; linkages were detected among 126 of the markers. The
      intact chromosomal DNAs of the parents and certain progeny were separated using
      pulsed field gel electrophoresis and hybridized with probes used to detect the
      RFLPs. In this way, 125 markers were assigned to specific chromosomes and
      linkages among 120 of the markers were confirmed. These linkages totalled 941
      centimorgans (cM). Several RFLPs and a reciprocal translocation were identified
      tightly linked to Tox1, a locus controlling host-specific virulence. Other
      differences in chromosome arrangement between the parents were also detected.
      Fourteen gaps of at least 40 cM were identified between linkage groups on the
      same chromosomes; the total map length was therefore estimated to be, at a
      minimum, 1501 cM. Fifteen A chromosomes ranging from about 1.3 megabases (Mb) to
      about 3.7 Mb were identified; one of the strains also has an apparent B
      chromosome. This chromosome appears to be completely dispensable; in some
      progeny, all of 15 markers that mapped to this chromosome were absent. The total
      genome size was estimated to be roughly 35 Mb. Based on these estimates of map
      length and physical genome size, the average kb/cM ratio in this cross was
      calculated to be approximately 23. This low ratio of physical length to map
      distance should make this RFLP map a useful tool for cloning genes.

PMID- 1346262
TI  - Identification of a Serratia entomophila genetic locus encoding amber disease in
      New Zealand grass grub (Costelytra zealandica).
AB  - Serratia entomophila UC9 (A1MO2), which causes amber disease in the New Zealand
      grass grub Costelytra zealandica, was subjected to transposon (TnphoA)-induced
      mutagenesis. A mutant (UC21) was found to be nonpathogenic (Path-) to grass grub
      larvae in bioassays and was shown, by Southern hybridization, to contain a single
      TnphoA insertion. This mutant failed to adhere to the gut wall (Adn-) of the
      larvae and also failed to produce pili (Pil-). A comparative study of the total
      protein profiles of wild-type S. entomophila UC9 and mutant UC21 revealed that
      the mutant lacked an approximately 44-kDa protein and overexpressed an
      approximately 20-kDa protein. Transfer of cosmids containing homologous wild-type
      sequences into mutant strain UC21 restored wild-type phenotypes (Path+, Pil+, and
      Adn+). One of the complementing cosmids (pSER107) conferred piliation on Pil-
      Escherichia coli HB101. The TnphoA insertion in UC21 was mapped within an 8.6-kb
      BamHI fragment common to the complementing cosmids, and we designated this gene
      locus amb-1. Six gene products with molecular masses of 44, 36, 34, 33, 20, and
      18 kDa were detected in E. coli minicells exclusive to the cloned 8.6-kb fragment
      (pSER201A). The 44-kDa gene product was not detected in E. coli minicells
      containing the cloned mutant fragment. Saturation mutagenesis of this fragment
      produced four unlinked insertional mutations with active fusions to TnphoA. These
      active fusions disrupted the expression of one or more gene products encoded by
      amb-1. The 8.6-kb fragment cloned in the opposite orientation (pSER201B)
      expressed only a 20-kDa protein. We propose that these are the products of
      structural and/or regulatory genes involved in adhesion and/or piliation which
      are prerequisites in the S. entomophila-grass grub interaction leading to amber
      disease.

PMID- 1346264
TI  - Increased muscarinic cholinergic receptor density on CD4+ lymphocytes in
      progressive multiple sclerosis.
AB  - We measured the density and affinity of muscarinic cholinergic receptors (MR) in
      29 chronic progressive and ten stable multiple sclerosis (MS) patients and 27
      control subjects using [3H]N-methyl-scopolamine. The density of MR on CD4+
      lymphocytes was significantly higher in chronic progressive MS (CPMS) than in
      controls (7.9 +/- 0.7 vs. 4.5 +/- 0.4 fmol/10(6) cells, p less than 0.001).
      Stable patients did not differ significantly from control subjects. Receptors of
      the M1 subtype were measured on CD4+ lymphocytes of nine patients and seven
      controls with the selective antagonist [3H]methylpirenzepine: M1/total receptor
      ratio was 64.1% in CPMS and 81.2% in controls, suggesting a selective increase of
      M2-type MR in CPMS. The findings may relate to parasympathetic denervation
      hypersensitivity of lymphocytes or to lymphocyte activation which is known to be
      associated with increased MR number.

PMID- 1346265
TI  - Putative periodontopathogens in "diseased" and "non-diseased" persons exhibiting
      poor oral hygiene.
AB  - The aim of the study was to assess the occurrence of some putative periodonto
      pathogens in "test" and "control" sites in "diseased" and "non-diseased" persons,
      respectively, from an adult rural Kenyan population exhibiting poor oral hygiene
      and widespread loss of attachment (LA). 14 persons (less than 35 years) were
      assigned to a "diseased" category on the basis of at least 4 sites with LA
      greater than or equal to 4 mm; at least 5 mm LA and a pocket greater than or
      equal to 4 mm interproximally in a lower incisor ("test" site): and less than 2
      mm LA and no pocket greater than or equal to 4 mm distal to a lower canine or
      mesial to a lower first premolar ("control" site). Age-matched "non-diseased"
      persons were identified on the basis of no sites with LA greater than 2 mm and no
      pockets greater than or equal to 4 mm associated with LA. Paperpoint samples from
      test and control sites as well as a scraping sample from the dorsum of tongue
      were examined for presence of Actinobacillus actinomycetemcomitans, Porphyromonas
      gingivalis, Bacteroides intermedius, B. melaninogenicus group, Capnocytophaga,
      Selenomonas spp., and Wolinella recta. P. gingivalis was found in 79% of test
      sites and 36% of control sites in "diseased" persons, and in 18% and 35% of test
      and control sites, respectively, in "non-diseased" persons. "No other bacterial
      group discriminated significantly between test and control sites or between
      diseased and non-diseased subjects. The surprisingly high occurrence of P.
      gingivalis in non-diseased subjects, both subgingivally and on tongue, indicates
      that deep periodontal pockets are not prerequisite ecological environments for P.
      gingivalis establishment.

PMID- 1346263
TI  - Interaction of the Bacillus subtilis glnRA repressor with operator and promoter
      sequences in vivo.
AB  - In vivo dimethyl sulfate footprinting of the Bacillus subtilis glnRA regulatory
      region under repressing and derepressing conditions demonstrated that the GlnR
      protein, encoded by glnR, interacts with two sites situated within and adjacent
      to the glnRA promoter. One site, glnRAo1, between positions -40 and -60 relative
      to the start point of transcription, is a 21-bp symmetrical element that has been
      identified as essential for glnRA regulation (H. J. Schreier, C. A. Rostkowski,
      J. F. Nomellini, and K. D. Hirschi, J. Mol. Biol. 220:241-253, 1991). The second
      site, glnRAo2, is a quasisymmetrical element having partial homology to glnRAo1
      and is located within the promoter between positions -17 and -37. The symmetry
      and extent of modifications observed for each site during repression and
      derepression indicated that GlnR interacts with the glnRA regulatory region by
      binding to both sites in approximately the same manner. Experiments using
      potassium permanganate to probe open complex formation by RNA polymerase
      demonstrated that transcriptional initiation is inhibited by GlnR. Furthermore,
      distortion of the DNA helix within glnRAo2 occurred upon GlnR binding. While
      glutamine synthetase, encoded by glnA, has been implicated in controlling glnRA
      expression, analyses with dimethyl sulfate and potassium permanganate ruled out a
      role for glutamine synthetase in directly influencing transcription by binding to
      operator and promoter regions. Our results suggested that inhibition of
      transcription from the glnRA promoter involves GlnR occupancy at both glnRAo1 and
      glnRAo2. In addition, modification of bases within the glnRAo2 operator indicated
      that control of glnRA expression under nitrogen-limiting (derepressing)
      conditions included the involvement of a factor(s) other than GlnR.

PMID- 1346266
TI  - Use of intravenous esmolol to predict efficacy of oral beta-adrenergic blocker
      therapy in patients with neurocardiogenic syncope.
AB  - The usefulness of esmolol in predicting the efficacy of treatment with an oral
      beta-adrenergic blocking agent was evaluated in 27 consecutive patients with
      neurocardiogenic syncope. Seventeen patients had a positive head-up tilt test
      response at baseline and 10 patients required intravenous isoproterenol for
      provocation of hypotension. All patients were then given a continuous esmolol
      infusion (500 micrograms/kg per min loading dose for 3 min followed by 300
      micrograms/kg per min maintenance dose) and rechallenged with a head-up tilt test
      at baseline or with isoproterenol. Of the 17 patients with a positive baseline
      tilt test response, 11 continued to have a positive response to esmolol
      challenge. Sixteen patients (including all 10 patients with a positive tilt test
      response with isoproterenol) exhibited a negative response to upright tilt during
      esmolol infusion. Irrespective of their response to esmolol infusion, all
      patients had a follow-up tilt test with oral metoprolol after an interval of
      greater than or equal to 5 half-lives of the drug. All 16 patients (100%) with a
      negative tilt test response during esmolol infusion had a negative tilt test
      response with oral metoprolol. Of the 11 patients with a positive tilt test
      response during esmolol infusion, 10 (90%) continued to have a positive response
      with oral metoprolol. It is concluded that in the electrophysiology laboratory,
      esmolol can accurately predict the outcome of a head-up tilt response to oral
      metoprolol. This information may be helpful in formulating a therapeutic strategy
      at the initial head-up tilt test in patients with neurocardiogenic syncope.

PMID- 1346267
TI  - Cytokine regulation of proliferation and ICAM-1 expression of human dermal
      microvascular endothelial cells in vitro.
AB  - The effects of recombinant human interleukin 1 alpha (IL-1 alpha), interleukin 1
      beta (IL-1 beta), interleukin 6 (IL-6), granulocyte/macrophage colony-stimulating
      factor (GM-CSF) and tumor necrosis factor-alpha (TNF) on the cell proliferation
      and the expression of intercellular adhesion molecule-1 (ICAM-1) were assessed in
      cultured human dermal microvascular endothelial cells (HDMEC). IL-1 alpha and IL
      1 beta stimulated the proliferation of HDMEC in a dose-dependent manner, whereas
      in control experiments using human umbilical vein endothelial cells (HUVEC), IL-1
      alpha and IL-1 beta did not stimulate HUVEC growth. Also GM-CSF stimulated the
      proliferation of HDMEC, whereas IL-6 did not affect endothelial cell growth in
      vitro. Treatment with IL-1 alpha, IL-1 beta, and TNF markedly increased the
      expression of ICAM-1 on HDMEC in a time- and dose-dependent manner, in contrast
      to IL-6 and GM-CSF. By pre-embedding immunoelectron microscopy, membrane-bound
      expression of ICAM-1 was visualized with pronounced labeling in areas of
      microvillous cell protrusions. The TNF-induced expression of ICAM-1 on HDMEC was
      blocked by co-incubation with a neutralizing antibody against TNF, but not with
      neutralizing antibodies against IL-1 alpha, IL-1 beta, or IL-6. In addition, co
      incubation of HDMEC with TNF and the retinoid compound acitretin, dexamethasone,
      or indomethacin did not abrogate the TNF-induced ICAM-1 expression. These results
      disclose IL-1 as a major, multifunctional endothelial cell-targeted cytokine and
      further confirm the concept that pro-inflammatory cytokines exert differential
      regulatory effects on dermal microvascular endothelial cell proliferation and
      expression of cell-adhesion molecules.

PMID- 1346268
TI  - Efficacy of epanolol versus metoprolol in angina pectoris: report from a Swedish
      multicentre study of exercise tolerance.
AB  - The efficacy of epanolol vs. metoprolol in stable angina pectoris was compared in
      114 patients recruited to a randomized double-blind cross-over study, consisting
      of a 4-week period on each drug. Epanolol (200 mg) or metoprolol (200 mg) was
      administered daily. Bicycle ergometry was performed at the end of each treatment
      period. The maximum workload was 134 +/- 18 W on epanolol and 133 +/- 37 W on
      metoprolol (NS). Values for resting heart rate (epanolol, 72 +/- 11 beats min-1;
      metoprolol, 64 +/- 12 beats min-1; P less than 0.001), systolic blood pressure
      (epanolol, 143 +/- 21 mmHg; metoprolol, 137 +/- 21 mmHg; P less than 0.05) and
      diastolic blood pressure (epanolol, 88 +/- 10 mmHg; metoprolol, 84 +/- 11 mmHg; P
      less than 0.01) were all higher on epanolol treatment. During exercise, the
      increase in heart rate and blood pressure was of similar magnitude during the two
      treatment periods, and these parameters did not differ significantly at the last
      identical workload. The rating of chest pain, fatigue and dyspnoea did not differ
      between the two drugs during submaximal or maximal exercise. In conclusion, 200
      mg of epanolol and metoprolol have similar efficacy with regard to exercise
      tolerance. As expected from the partial agonist activity present in epanolol but
      not in metoprolol, the former drug resulted in a higher heart rate and blood
      pressure at rest. The observed increase in these parameters during exercise was
      similar for both drugs.

PMID- 1346270
TI  - Heat-stable antigen is a costimulatory molecule for CD4 T cell growth.
AB  - Optimal induction of clonal expansion by normal CD4 T cells requires a ligand
      that can engage the T cell receptor as well as functionally defined costimulatory
      activity on the same antigen-presenting cell surface. While the presence of
      effective costimulation induces proliferation, T cell receptor ligation in its
      absence renders T cells inactive or anergic. The molecular basis of this
      costimulatory activity remains to be defined. Here we describe a monoclonal
      antibody that can block the costimulatory activity of splenic accessory cells.
      Treatment with this antibody not only blocks the proliferation of CD4 T cells to
      a T cell receptor ligand, but also induces T cell nonresponsiveness to subsequent
      stimulation. Sequence analysis of the antigen recognized by this antibody
      indicates that it recognizes a protein that is identical to heat-stable antigen.
      Gene transfer experiments directly demonstrate that this protein has
      costimulatory activity. Thus, heat-stable antigen meets the criteria for a
      costimulator of T cell clonal expansion.

PMID- 1346271
TI  - Acquired Mls-1a-like clonal deletion in Mls-1b mice.
AB  - BALB/c mice (H-2d, Mls-1b) from one colony progressively modify their T cell
      repertoire during aging, by deleting T cells that express products of the V beta
      6 and V beta 8.1 genes of the T cell receptor. Clonal deletion occurs only in 50%
      of mice between 27 and 43 wk of age, affecting thymus, spleen, and lymph node T
      cells. The phenomenon is progressive and seems to affect nearly all thymuses
      between 14 and 19 wk of age. CD4+CD8- mature T cells are more affected than CD4
      CD8+ cells. In the thymus, deletion occurs at the stage of immature J11d+ cells
      expressing a high level of V beta 6, while J11d+V beta 6low-expressing cells are
      not modified. Clonal deletion is thus an early phenomenon that deletes cells of
      the immature generative compartment in the thymus. This Mls-1a-like clonal
      deletion is associated neither with the expression of an Mls-1a-like antigen that
      could be identified in mixed lymphocyte reaction in vitro, nor with the presence
      of Mtv-7, the endogenous mouse mammary tumor virus (MMTV) proviral loci. Spleen
      cells, bone marrow cells, and total thymocytes injected into newborn thymuses
      cannot induce V beta 6+ cell deletion. However, newborn thymuses grafted into old
      BALB/c mice behave like their recipients, suggesting that a new antigen, present
      in these old BALB/c mice, is indeed able to induce an Mls-1a-like clonal
      deletion. As other BALB/c colonies tested do not behave in same way, the
      hypothesis of a new exogenous deleting factor rather than a genetic transmission
      is likely. This may suggest that acquired clonal deletion is a more common
      phenomenon than expected, and may be the spontaneous reaction of the immune
      system to the introduction of a new retrovirus or other superantigen.

PMID- 1346269
TI  - Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency
      virus-infected asymptomatic individuals.
AB  - In immature thymocytes, T cell receptor for antigen (TCR) mobilization leads to
      an active T cell suicide process, apoptosis, which is involved in the selection
      of the T cell repertoire. We have proposed that inappropriate induction of such a
      cell death program in the mature CD4+ T cell population could account for both
      early qualitative and late quantitative CD4+ T lymphocyte defects of human
      immunodeficiency virus (HIV)-infected individuals (Ameisen, J.C., and A. Capron.
      1991. Immunol. Today. 4:102). Here, we report that the selective failure of CD4+
      T cells from 59 clinically asymptomatic HIV-infected individuals to proliferate
      in vitro to TCR mobilization by major histocompatibility complex class II
      dependent superantigens and to pokeweed mitogen (PWM) is due to an active CD4+ T
      cell death process, with the biochemical and ultrastructural features of
      apoptosis. Activation-induced cell death occurred only in the CD4+ T cell
      population from HIV-infected asymptomatic individuals and was not observed in T
      cells from any of 58 HIV-seronegative controls, including nine patients with
      other acute or chronic infectious diseases. Activation-induced CD4+ T cell death
      was prevented by cycloheximide, cyclosporin A, and a CD28 monoclonal antibody
      (mAb). The CD28 mAb not only prevented apoptosis but also restored T cell
      proliferation to stimuli, including PWM, superantigens, and the tetanus and
      influenza recall antigens. These findings may have implications for the
      understanding of the pathogenesis of acquired immune deficiency syndrome and for
      the design of specific therapeutic strategies.

PMID- 1346274
TI  - The cumulative risk of AIDS as the CD4 lymphocyte count declines.
AB  - A method is proposed for assessing the cumulative risk of various AIDS-defining
      conditions as the CD4 lymphocyte count declines in HIV-infected individuals. The
      method is analogous to survival analysis but is based on the CD4 lymphocyte count
      rather than on time. Thus, the level to which the CD4 lymphocyte count has
      declined, rather than the length of time since seroconversion, is considered as
      an individual's survival interval. The survival interval may be censored (due to
      lack of follow-up) or treated as an interval to failure (if the individual
      develops AIDS). The Kaplan-Meier (product-limit) estimates, of the proportion of
      individuals developing AIDS before reaching a given low CD4 lymphocyte count, may
      be useful for determining when prophylactic treatment should begin.

PMID- 1346272
TI  - Human mature T cells that are anergic in vivo prevail in SCID mice reconstituted
      with human peripheral blood.
AB  - In these studies we have characterized the human cells that repopulate severe
      combined immunodeficient (SCID) mice after injection of adult peripheral blood or
      cord blood (hu-PBL-SCID mice). In all organs of the chimeras, and at any time
      point tested, single-positive (CD4+ or CD8+) T cells that expressed the
      alpha/beta T cell receptor (TCR) prevailed. All T cells were CD45RO+ and the
      majority were also HLA-DR+. Thus, the human T cells in the chimeras exhibited the
      phenotype of mature, memory cells that showed signs of recent activation. Cell
      cycle studies revealed a mitotically active human T cell population in the murine
      host. However, when freshly isolated from the chimeras, the human T cells were
      refractory to stimulation by anti-CD3 antibody but proliferated in response to
      exogenous interleukin 2. Chimera-derived human T cell lines retained this state
      of unresponsiveness to TCR-triggered proliferation for 4-6 wk in vitro.
      Subsequently, the T cell lines developed responses to anti-CD3 stimulation and 9
      of 11 of the lines also proliferated in response to splenic stimulator cells of
      SCID mice. These data demonstrate that the human T cells are in a state of
      reversible anergy in the murine host and that xenoreactivity might play a
      critical role in hu-PBL-SCID mice. Mechanisms that may determine repopulation of
      SCID mice with human peripheral blood mononuclear cells are discussed.

PMID- 1346275
TI  - Synthesis and evaluation of some water-soluble prodrugs and derivatives of taxol
      with antitumor activity.
AB  - The synthesis and evaluation of some 2'- and 7-amino acid derivatives of taxol
      (1) are reported. Reaction of taxol with N-protected amino acids gave 2'-N
      protected amino acid esters of taxol. However, deprotection of the amino group
      and subsequent isolation of products were complex and only successful when formic
      acid was used to deprotect a t-BOC protecting group. Esterification of taxol
      using N,N-dialkylated amino acids gave 2'-amino acid esters of taxol, 2'-(N,N
      dimethylglycyl)taxol (4) and 2'-[3-(N,N-diethylamino)propionyl]taxol as its
      methanesulfonic acid salt (5b), in good yield. The 7-derivatives, 7-(N,N
      dimethylglycyl)taxol (9) and 7-L-alanyltaxol (12), were prepared by two alternate
      methods. In the first approach, the 2'-hydroxyl group was protected using the
      [(2,2,2-trichloro-ethyl)oxy]carbonyl, or troc, protecting group followed by the
      esterification of the 7-hydroxyl and subsequent deprotection of the amino and
      troc groups. In the second approach, taxol was allowed to react with more than 2
      molar equiv of the N-protected amino acids or N,N-dialkylated amino acids to give
      2',7-diamino acid esters of taxol. For the protected amino acids, the
      deprotection of the amino group followed by removal of the 2'-substituent gave
      the 7-amino acid esters of taxol. The methanesulfonic acid salts of both 2'- and
      7-amino acid esters showed improved solubility ranging from 2 to greater than 10
      mg/mL. The 7-derivatives were effective in promoting microtubule assembly in
      vitro while 2'-derivatives showed little in vitro activity. The derivatives 2'
      (N,N-dimethylglycyl)taxol (4) and 2'-[3-(N,N-diethylamino)propionyl]taxol (5)
      inhibited proliferation of B16 melanoma cells to an extent similar to that of
      taxol, while the other derivatives were about 50% as cytotoxic. In a mammary
      tumor screen, 2'-[3-(N,N-diethylamino)propionyl]taxol showed the greatest
      antitumor activity compared to the other analogues. The lower activities of the 7
      derivatives in inhibiting tumor growth and melanoma cell proliferation (although
      they were almost as active as taxol in inducing microtubule assembly in vitro)
      may be due to differences in drug uptake by the cells. The similar cytotoxic and
      antitumor activities of the 2'-analogues and taxol can be explained by their
      conversion to taxol or an active taxol metabolite. Therefore, the 2'-analogues
      appear to behave as prodrugs and have the potential to be developed as
      chemotherapeutic agents.

PMID- 1346273
TI  - The OX-44 molecule couples to signaling pathways and is associated with CD2 on
      rat T lymphocytes and a natural killer cell line.
AB  - The MRC OX-44 molecule, which is expressed on all peripheral leukocytes,
      identifies the subset of thymocytes capable of proliferating in response to
      alloantigens and lectins (Paterson, D.J., J.R. Green, W.A. Jefferies, M.
      Puklavec, and A.F. Williams. 1987. J. Exp. Med. 165:1). When we isolated
      monoclonal antibodies (mAbs) on the basis of their ability to activate the
      phosphatidylinositol signaling pathway in RNK-16 cells (a rat leukemia line with
      natural killer activity), three of the resulting mAbs recognized the OX-44
      molecule. Addition of these mAbs to RNK-16 elicits protein tyrosine
      phosphorylation, generates inositol phosphates, and increases the concentration
      of cytoplasmic free calcium. These responses require the addition of intact mAb
      and are not observed with F(ab')2 fragments. One of these mAbs (7D2) is mitogenic
      for freshly isolated rat splenic T cells and synergizes with a mAb to the T cell
      antigen receptor in this activation. A 50-60-kD glycoprotein coprecipitates with
      the OX-44 molecule from RNK-16 cells and rat splenic T cells. Peptide mapping and
      reprecipitation studies indicate that the coprecipitating molecule is CD2. Thus,
      the OX-44 molecule can couple to multiple signaling pathways and associates with
      CD2 on both RNK-16 and rat T cells.

PMID- 1346276
TI  - Preparation and opioid activity of analogues of the analgesic dipeptide 2,6
      dimethyl-L-tyrosyl-N-(3-phenylpropyl)-D-alaninamide.
AB  - A number of analogues of the recently disclosed analgesic dipeptide 2,6-dimethyl
      L-tyrosyl-D-alanine-phenylpropylamide (SC-39566, 2) were prepared. These
      analogues contained oxymethylene, aminomethylene, ketomethylene, bismethylene,
      and trans double bond (including vinyl fluoride) isosteric replacements for the
      amide bond between the D-alanine and phenylpropylamine units in 2. These
      compounds were tested in opioid binding assays and in the mouse writhing assay
      for analgesic activity. Though not as potent as 2, the oxymethylene, and trans
      double bond isosteres showed analgesic activity. The aminomethylene analogues
      also showed binding activity in subnanomolar concentrations at the mu receptor.
      The amide bond between 2,6-dimethyl-L-tyrosine and D-alanine units seems to be
      critical for opioid activity.

PMID- 1346277
TI  - Spontaneous retroperitoneal hemorrhage.

PMID- 1346278
TI  - Medical care following HIV testing.

PMID- 1346279
TI  - Risk of strut fracture of Bjork-Shiley valves.
AB  - The incidence of and factors that predispose to outlet strut fracture of Bjork
      Shiley heart valves are still not known. To obtain such information a
      retrospective cohort study was conducted on all 2303 patients in the Netherlands
      with a 60 degrees convexo-concave (60 degrees CC) or a 70 degrees convexo-concave
      (70 degrees CC) Bjork-Shiley heart valve. Patients have been followed-up for a
      mean of 6.6 years (range 1-4271 days). 42 cases of mechanical failure due to
      outlet strut fracture have been recorded-6 of the 7 patients with fracture of the
      aortic valve died, as did 18 of the 35 patients with fracture of the mitral
      valve. Multivariate analysis identified wide opening angle (70 degrees), large
      valve size (greater than or equal to 29 mm diameter), and young age (less than 50
      years) as risk factors for outlet strut fracture. For large 70 degrees CC mitral
      valves the cumulative risk of outlet strut fracture after 8 years was 17.4% (95%
      CI 9.1-31.6). Unlike previous findings, this excessive risk applied to late as
      well as to early batches of valves. In patients with a large 60 degrees CC mitral
      valve the cumulative risk after 8 years was 4.2% (95% CI 2.7-6.5). The incidence
      rate of outlet strut fracture in 60 degrees CC and 70 degrees CC valves (aortic
      and mitral) was constant over time. Overall survival since implantation was
      better for patients with 60 degrees CC prostheses than for those with 70 degrees
      CC prostheses; the adjusted hazard ratio for mortality for patients receiving a
      70 degrees CC prosthesis was 1.5 (95% CI 1.1-2.0). Together with the low (24%)
      necropsy rate, this ratio suggests that the reported incidence of strut fracture
      for the 70 degrees CC valves is an underestimate. The data indicate that
      prophylactic replacement of 60 degrees CC and 70 degrees CC valves is advisable
      for selected groups of patients. Since the case-fatality rate is 50% for
      emergency replacement of faulty valves, patients suspected of Bjork-Shiley heart
      valve failure should be referred without delay to a cardiothoracic centre.

PMID- 1346280
TI  - Breast milk and subsequent intelligence quotient in children born preterm.
AB  - There is considerable controversy over whether nutrition in early life has a long
      term influence on neurodevelopment. We have shown previously that, in preterm
      infants, mother's choice to provide breast milk was associated with higher
      developmental scores at 18 months. We now report data on intelligence quotient
      (IQ) in the same children seen at 7 1/2-8 years. IQ was assessed in 300 children
      with an abbreviated version of the Weschler Intelligence Scale for Children
      (revised Anglicised). Children who had consumed mother's milk in the early weeks
      of life had a significantly higher IQ at 7 1/2-8 years than did those who
      received no maternal milk. An 8.3 point advantage (over half a standard
      deviation) in IQ remained even after adjustment for differences between groups in
      mother's education and social class (p less than 0.0001). This advantage was
      associated with being fed mother's milk by tube rather than with the process of
      breastfeeding. There was a dose-response relation between the proportion of
      mother's milk in the diet and subsequent IQ. Children whose mothers chose to
      provide milk but failed to do so had the same IQ as those whose mothers elected
      not to provide breast milk. Although these results could be explained by
      differences between groups in parenting skills or genetic potential (even after
      adjustment for social and educational factors), our data point to a beneficial
      effect of human milk on neurodevelopment.

PMID- 1346281
TI  - High-frequency diaphragmatic flutter: symptoms and treatment by carbamazepine.
AB  - Classic diaphragmatic flutter, a rare disorder associated with dyspnoea, thoracic
      or abdominal wall pain, and epigastric pulsations, is caused by involuntary
      contractions of the diaphragm with a frequency of 0.5-8.0 Hz. We have seen three
      patients with diaphragmatic flutter of higher frequency not associated with
      respiratory disease. The patients presented with longstanding oesophageal
      belching, hiccups, and retching, respectively. The diagnosis was established by
      the presence on electromyography of the diaphragm and scalene and parasternal
      intercostal muscles of repetitive discharges of 9-15 Hz. Spirographic tracings,
      especially those of volume or flow vs time, showed similar high-frequency
      oscillations superimposed on tidal respiratory movements. Treatment with
      carbamazepine 200-400 mg three times daily led to disappearance or great
      improvement of flutter and clinical symptoms in all three patients. The
      phenomenon was not seen in other patients with chronic hiccups or oesophageal
      belching or in patients without these symptoms who had undergone electromyography
      or spirography for other reasons. Thus, high-frequency diaphragmatic flutter
      seems to be a new disease entity. The response to carbamazepine, which suggests
      that the flutter causes the symptoms, requires further study.

PMID- 1346282
TI  - Anti-GOR and hepatitis C virus in autoimmune liver diseases.
AB  - Anti-GOR is an autoantibody found in hepatitis C virus (HCV) infection. We have
      studied the specificity of this antibody for HCV infection in various groups of
      autoimmune liver diseases. Anti-HCV was detected by a second generation HCV
      enzyme-linked immunosorbent assay in 14 of 29 patients with liver-kidney
      microsomal (LKM-1) -antibody-positive autoimmune hepatitis type 2 and in all 6
      control patients with HCV-RNA-positive chronic hepatitis C. Anti-HCV was not
      found in those with antinuclear-antibody-positive autoimmune hepatitis type 1 (10
      patients), with soluble-liver-protein-antibody-positive autoimmune hepatitis type
      3 (8), with primary biliary cirrhosis (9), with systemic lupus erythematosus
      (SLE) (10), or in healthy controls (13). Anti-GOR was detected in 11 of 14
      patients with autoimmune hepatitis type 2 who were all positive for anti-HCV but
      only in 1 of 15 LKM-1 patients who were negative for anti-HCV. We did not find
      anti-GOR in any other group of autoimmune liver disease, SLE, or control sera,
      but this antibody was detected in 3 of 6 patients with chronic hepatitis C.
      Autoimmune hepatitis type 2 patients who were anti-GOR positive and anti-HCV
      positive were less likely to be female, were older (p less than 0.001), and had
      lower LKM-1 antibody titres (p less than 0.001), lower disease activity, and
      responded less effectively to immuno- suppression than did those who were anti
      HCV negative/anti-GOR negative. The findings show that anti-GOR reflects HCV
      specific autoimmunity. HCV seems to induce autoimmunity to both GOR (an HCV
      specific autoepitope) and LKM-1 (an epitope that is also recognised by autoimmune
      hepatitis sera of a different cause). Anti-GOR and LKM-1 antibodies contribute to
      a better differentiation of chronic hepatitis, a finding that has therapeutic
      implications.

PMID- 1346283
TI  - Indomethacin and postprandial gallbladder emptying.
AB  - Patients with gallstone disease commonly have impaired gallbladder emptying. To
      see whether non-steroidal anti-inflammatory drugs (NSAIDs) prevent gallstone
      formation by improving gallbladder emptying, we assessed the effect of
      indomethacin on postprandial emptying in healthy subjects and in patients with
      gallstone disease. Subjects received indomethacin 25 mg three times a day for a
      week and matching placebo for another week. Compared with placebo, indomethacin
      improved postprandial gallbladder emptying in all 7 patients with gallstone
      disease. This finding was not recorded in healthy subjects with normal
      gallbladders. The prevention of gallstone formation associated with ingestion of
      NSAIDs may be due mainly to a prokinetic effect on the gallbladder since there is
      no evidence to suggest that these drugs affect cholesterol crystal nucleation at
      ordinary therapeutic doses in man or animals.

PMID- 1346284
TI  - Detection of full fragile X mutation.
AB  - In fragile X syndrome, the most common inherited cause of mental deficiency, the
      underlying mutation is a large increase in the number of CGG repeats in a gene on
      chromosome X. We have developed a polymerase chain reaction (PCR) method to
      amplify across the full mutation in affected individuals. In this report, a
      fragile X family including a positive prenatally diagnosed fetus was analysed by
      PCR, and the results are consistent with direct genomic Southern blot analysis.
      Genetic screening of at-risk populations for fragile X can now be achieved by PCR
      rapidly, inexpensively, and on small samples.

PMID- 1346286
TI  - Pacifiers, passive behaviour, and pain.

PMID- 1346285
TI  - Intrarectal challenge of macaques vaccinated with formalin-inactivated simian
      immunodeficiency virus.
AB  - Macaques can be protected from intravenous infection with simian immunodeficiency
      virus (SIV) by vaccination with chemically inactivated virus. However, protection
      against infection via a mucosal surface has not been demonstrated. We vaccinated
      four rhesus macaques with formalin-inactivated SIV given intramuscularly. These
      monkeys, which had remained virus free for 10 months after intravenous challenge
      with SIV, were given a further dose of vaccine and together with four
      unvaccinated controls were challenged intrarectally with SIV. Subsequently, virus
      was isolated from all control animals on five successive occasions, but the
      vaccinated animals remained free of virus. Proviral DNA could not be detected in
      peripheral blood mononuclear cells from the vaccinated animals. Preliminary data
      indicate that vaccinated animals make a local antibody response.

PMID- 1346288
TI  - Is pathology dangerous to health?

PMID- 1346287
TI  - Atypical treatments for schizophrenia.

PMID- 1346289
TI  - Failure to treat heart failure.

PMID- 1346290
TI  - Psychogenic vomiting--a disorder of gastrointestinal motility?

PMID- 1346291
TI  - Long-term follow-up of childhood Henoch-Schonlein nephritis.
AB  - A study of long-term outcome of 78 subjects who had had Henoch-Schonlein
      nephritis during childhood (at a mean of 23.4 years after onset) shows that
      severity of clinical presentation and initial findings on renal biopsy correlate
      well with outcome but have poor predictive value in individuals. 44% of patients
      who had nephritic, nephrotic, or nephritic/nephrotic syndromes at onset have
      hypertension or impaired renal function, whereas 82% of those who presented with
      haematuria (with or without proteinuria) are normal. 17 patients deteriorated
      clinically from an initial assessment in 1971; 7 of these had apparently
      completely recovered in 1976. 16 of 44 full-term pregnancies were complicated by
      proteinuria and/or hypertension, even in the absence of active renal disease.
      These findings indicate that childhood Henoch-Schonlein nephritis requires long
      term follow-up, especially during pregnancy.

PMID- 1346292
TI  - Customised antenatal growth charts.
AB  - Charts for fetal growth do not take physiological variables into account. We have
      therefore designed a computer-generated antenatal chart that can be easily
      "customised" for each individual pregnancy, taking the mother's characteristics
      and birthweights from previous pregnancies into consideration. The adjusted
      birthweight range expected at 40 weeks' gestation is combined with a standard,
      longitudinal ultrasound-derived curve for intrauterine weight gain. Review at the
      Queen's Medical Centre, Nottingham, UK, of 4179 pregnancies with ultrasound
      confirmed dates showed that, in addition to gestation and sex, maternal weight at
      first antenatal-clinic visit, height, ethnic group, and parity were significant
      determinants of birthweight in our population. Correction factors were calculated
      for each of these variables and entered into a computer program to adjust the
      normal birthweight centile limits. With adjusted centiles we found that 28% of
      babies conventionally designated small for gestational age (less than 10th
      centile) and 22% of those designated large (greater than 90th centile) were in
      fact within normal limits for the pregnancy. Conversely, 24% and 26% of babies
      identified as small or large, respectively, with adjusted centiles were "missed"
      by conventional unadjusted centile assessment. Adjustment for physiological
      variables will make assessment of fetal growth more precise and reduce
      unnecessary investigations, interventions, and parental anxiety.

PMID- 1346294
TI  - Drug dependence with oestrogen replacement therapy.
AB  - Dependence on some drugs can be hard to recognize. Hormone replacement therapy
      (HRT) has been widely prescribed only in the past two decades, and the
      indications for treatment and the risk/benefit ratio are still disputed.
      Oestrogens are psychoactive: they lift mood, can be given by injection, and their
      use has powerful psychological effects. Reports of women with supraphysiological
      oestradiol concentrations may represent tolerance and withdrawal. Dependence on
      substances occurring naturally in the body has been reported before. We propose
      that HRT dependence occurs.

PMID- 1346293
TI  - Sudden cardiac tamponade after chemotherapy for marrow transplantation in
      thalassaemia.
AB  - Published work suggests that cardiac tamponade occurs only occasionally after
      bone-marrow transplantation (BMT) but the worrying number of cases encountered in
      the transplant programme in Pesaro, Italy, has led to an analysis of this
      complication. Cardiac tamponade occurred in 8 (2%) of 400 consecutive
      thalassaemic patients during conditioning for or within a month of BMT. 6 cases
      were fatal; these represented 9% of all causes of death and 29% of those
      occurring between start of conditioning regimen and 30 days post transplant. The
      syndrome was characterised by sudden onset of circulatory shock and cardiac
      arrest. The only effective treatment was immediate fluid removal. The absence of
      myocardial lesions and the complete resolution of the syndrome after
      pericardiocentesis suggest that the pericardial membranes played the main part in
      the pathogenesis of the syndrome. Since irradiation was not part of the
      conditioning regimen and since 3 of the affected patients had bacteraemia, the
      triggering factor for the syndrome could have been the drugs used for
      conditioning, acting alone or together with bacteraemia and trauma. The frequency
      with which we encountered the syndrome, and the similarity among our patients in
      clinical picture, and in characteristics of the effusion, indicate that cardiac
      tamponade occurring in thalassaemic patients after start of chemotherapy as
      conditioning for BMT is a specific syndrome requiring rapid treatment.

PMID- 1346295
TI  - Robust dismissal of a claim on chemical sensitisation.

PMID- 1346296
TI  - Case against antibiotic prophylaxis for dental treatment of patients with joint
      prostheses.

PMID- 1346297
TI  - Clinical aspects of Mycoplasma pneumoniae infection.

PMID- 1346298
TI  - Mood and peak flow in asthma.

PMID- 1346300
TI  - Acute myocardial infarction among civilians in Zagreb city area.

PMID- 1346299
TI  - Gallium (aluminium) transferrin binding in Alzheimer's disease.

PMID- 1346301
TI  - Factor VIII solutions in pre-filled syringes.

PMID- 1346302
TI  - Hepatitis A vaccination.

PMID- 1346303
TI  - Occupationally acquired hepatitis C virus infection.

PMID- 1346304
TI  - Evaluating mumps vaccines.

PMID- 1346305
TI  - Occupationally acquired hepatitis C virus infection.

PMID- 1346306
TI  - Vertical transmission of HTLV-I.

PMID- 1346307
TI  - Efficacy of cytarabine in progressive multifocal leucoencephalopathy in AIDS.

PMID- 1346308
TI  - Iohexol to monitor GFR.

PMID- 1346309
TI  - Duration of efficacy of anti-anginal drugs.

PMID- 1346310
TI  - Nitrous oxide as neurotransmitter.

PMID- 1346311
TI  - Six pregnancies following donation of both oocytes and sperm.

PMID- 1346312
TI  - Opportunistic Capnocytophaga canimorsus infection.

PMID- 1346314
TI  - Detection of wheat contamination in dietary non-wheat products by PCR.

PMID- 1346313
TI  - Hypercalcaemia due to all-trans retinoic acid.

PMID- 1346315
TI  - Long-term care in the UK.

PMID- 1346316
TI  - Long-term care in the UK.

PMID- 1346317
TI  - Long-term care in the UK.

PMID- 1346318
TI  - Knowledge-based systems for monitoring and evaluation of health services in
      developing countries.

PMID- 1346319
TI  - MRC funding.

PMID- 1346321
TI  - Nursing research.

PMID- 1346320
TI  - Elderly drivers.

PMID- 1346322
TI  - Secrecy and product information.

PMID- 1346323
TI  - X-linked lymphoproliferative disease.

PMID- 1346324
TI  - Pristinamycin for Enterococcus faecium resistant to vancomycin and gentamicin.

PMID- 1346325
TI  - Misoprostol, mifepristone, and abortion.

PMID- 1346326
TI  - Sense of smell after gentamicin nose-drops.

PMID- 1346327
TI  - Simvastatin and lipoprotein(a)

PMID- 1346328
TI  - The patient's view of breast cancer trials.

PMID- 1346330
TI  - The patient's view of breast cancer trials.

PMID- 1346329
TI  - Breast cancer found at screening and previous detection by women themselves.

PMID- 1346331
TI  - Protective role for CD8 cells in tuberculosis.

PMID- 1346332
TI  - Omeprazole and oesophageal stricture.

PMID- 1346333
TI  - Overexpression of glutathione S-transferase and elevation of thiol pools in a
      multidrug-resistant human colon cancer cell line.
AB  - A human colon cancer cell line with acquired multidrug resistance (MDR) was
      assayed for the intracellular GSH level and the activity of GSH-S-transferase
      (GST), which catalyzes the conjugation reaction of electrophilic drugs with GSH.
      The GSH level and GST activity (as measured with 1-chloro-2,4-dinitrobenzene)
      were elevated in the resistant cells by 1.7-fold and 2-fold, respectively. This
      elevated catalytic activity of the resistant cells was reflected in a 2-fold
      increase in GST-pi mRNA, which was not the result of gene amplification. In
      addition, buthionine sulfoximine, a specific inhibitor of GSH synthesis,
      significantly increased Adriamycin sensitivity in both the MDR and the parental
      cells, affecting the former more than the latter. The effects seen with
      buthionine sulfoximine were not seen with puromycin and actinomycin D. A dramatic
      overexpression of mdr1, a P-glycoprotein gene responsible for the MDR phenotype,
      was also observed in the MDR cells. In contrast, none of these products (i.e.,
      mdr P-glycoprotein, GSH level, total GST activity, GST-pi gene copy, and GST-pi
      mRNA level) was elevated in HeLa cells resistant to cisplatin and some alkylating
      agents, supporting the notion that the acquisition of cisplatin resistance
      differs from the mechanism of MDR. These results indicate that the intrinsic GSH
      level and GST-pi activity affect anthracycline resistance per se and not MDR in
      the human colon cancer cells.

PMID- 1346335
TI  - Fetal liver pro-B and pre-B lymphocyte clones: expression of lymphoid-specific
      genes, surface markers, growth requirements, colonization of the bone marrow, and
      generation of B lymphocytes in vivo and in vitro.
AB  - We describe here the development and characterization of the FLS4.1 stromal line
      derived from 15-day fetal liver of BALB/c embryos and defined culture conditions
      that efficiently support the cloning and long-term growth of nontransformed B
      220+ 14-day fetal liver cells at two stages of B-cell development, namely, pro-B
      lymphocytes (immunoglobulin [Ig] genes in germ line configuration) and pre-B
      cells (JH-rearranged genes with both light-chain Ig genes in the germ line
      state). All B-cell precursor clones require recombinant interleukin-7 (rIL-7) and
      FLS4.1 stromal cells for continuous growth in culture, but pro-B lymphocyte
      clones can also proliferate in rIL-3. None proliferate in rIL-1, rIL-2, rIL-4,
      rIL-5, rIL-6, or leukemia inhibitory factor. FLS4.1 stromal cells synthesize mRNA
      for Steel factor but not for IL-1 to IL-7; all pro-B and pre-B clones express c
      Kit, the receptor for Steel factor, and a c-Kit-specific antibody inhibits the
      enhanced proliferative response of fetal liver B-220+ B-cell precursors supported
      by FLS4.1 stromal cells and exogenous rIL-7 but does not affect that promoted by
      rIL-7 alone. Northern (RNA) blot analysis of the expression of the MB-1, lambda
      5, Vpre-B, c mu, RAG-1, and RAG-2 genes in pro-B and pre-B clones show that
      transcription of the MB-1 gene precedes IgH gene rearrangement and RNA synthesis
      from c mu, RAG-1, RAG-2, lambda 5, and Vpre-B genes. All clones at the pre-B-cell
      stage synthesize mRNA for c mu, RAG-1, and RAG-2 genes; transcription of the
      lambda 5 and Vpre-B genes seems to start after D-to-JH rearrangement in B-cell
      precursors, indicating that the proteins encoded by either gene are not required
      for B-cell progenitors to undergo D-to-JH gene rearrangement. These findings mark
      transcription of the MB-1 gene as one of the earliest molecular events in
      commitment to develop along the B-lymphocyte pathway. Indeed, both pro-B and pre
      B clones can generate in vitro and in vivo B lymphocytes but not T lymphocytes;
      moreover, these clones do not express the CD3-gamma T-cell-specific gene, nor do
      they have rearranged gamma, delta, or beta T-cell antigen receptor genes.

PMID- 1346334
TI  - Anti-oncogenic activity of signalling-defective epidermal growth factor receptor
      mutants.
AB  - Overexpression and autocrine activation of the epidermal growth factor receptor
      (EGF-R) cause transformation of cultured cells and correlate with tumor
      progression in cancer patients. Dimerization and transphosphorylation are crucial
      events in the process by which receptors with tyrosine kinase activity generate
      normal and transforming cellular signals. Interruption of this process by
      inactive receptor mutants offers the potential to inhibit ligand-induced cellular
      responses. Using recombinant retroviruses, we have examined the effects of
      signalling-incompetent EGF-R mutants on the growth-promoting and transforming
      potential of ligand-activated, overexpressed wild-type EGF-R and the v-erbB
      oncogene product. Expression of a soluble extracellular EGF-R domain had little
      if any effect on the growth and transformation of NIH 3T3 cells by either
      tyrosine kinase. However, both a kinase-negative EGF-R point mutant (HERK721A)
      and an EGF-R lacking 533 C-terminal amino acids efficiently inhibited wild-type
      EGF-R-mediated, de novo DNA synthesis and cell transformation in a dose-dependent
      manner. Furthermore, coexpression with the v-erbBES4 oncogene product in NIH 3T3
      cells resulted in transphosphorylation of the HERK721A mutant receptor and
      reduced soft-agar colony growth but had no effect in a focus formation assay.
      These results demonstrate that signalling-defective receptor tyrosine kinase
      mutants differentially interfere with oncogenic signals generated by either
      overexpressed EGF-R or the retroviral v-erbBES4 oncogene product.

PMID- 1346337
TI  - A controlled trial of early versus late treatment with zidovudine in symptomatic
      human immunodeficiency virus infection. Results of the Veterans Affairs
      Cooperative Study.
AB  - BACKGROUND: Zidovudine is recommended for asymptomatic and early symptomatic
      human immunodeficiency virus (HIV) infection. The best time to initiate
      zidovudine treatment remains uncertain, however, and whether early treatment
      improves survival has not been established. METHODS: We conducted a multicenter,
      randomized, double-blind trial that compared early zidovudine therapy (beginning
      at 1500 mg per day) with late therapy in HIV-infected patients who were
      symptomatic and had CD4+ counts between 0.2 x 10(9) and 0.5 x 10(9) cells per
      liter (200 to 500 per cubic millimeter) at entry. Those assigned to late therapy
      initially received placebo and began zidovudine when their CD4+ counts fell below
      0.2 x 10(9) per liter (200 per cubic millimeter) or when the acquired
      immunodeficiency syndrome (AIDS) developed. RESULTS: During a mean follow-up
      period of more than two years, there were 23 deaths in the early-therapy group (n
      = 170) and 20 deaths in the late-therapy group (n = 168) (P = 0.48; relative risk
      [late vs. early], 0.81; 95 percent confidence interval, 0.44 to 1.59). In the
      early-therapy group, 28 patients progressed to AIDS, as compared with 48 in the
      late-therapy group (P = 0.02; relative risk, 1.76; 95 percent confidence
      interval, 1.1 to 2.8). Early therapy increased the time until CD4+ counts fell
      below 0.2 x 10(9) per liter (200 per cubic millimeter), and it produced more
      conversions from positive to negative for serum p24 antigen. Early therapy was
      associated with more anemia, leukopenia, nausea, vomiting, and diarrhea, whereas
      late therapy was associated with more skin rash. CONCLUSIONS: In symptomatic
      patients with HIV infection, early treatment with zidovudine delays progression
      to AIDS, but in this controlled study it did not improve survival, and it was
      associated with more side effects.

PMID- 1346336
TI  - The Oct-1 POU domain mediates interactions between Oct-1 and other POU proteins.
AB  - The POU domain is the conserved DNA binding domain of a family of gene regulatory
      proteins. It consists of a POU-specific domain and a POU homeodomain, connected
      by a variable linker region. Oct-1 is a ubiquitously expressed POU domain
      transcription factor. It binds to the canonical octamer sequence (ATGCAAAT) as a
      monomer. Here we show by chemical cross-linking and protein affinity
      chromatography that the Oct-1 POU domain monomers can interact in solution. This
      association requires both the POU homeodomain and the POU-specific domain. The
      interaction is transient in solution and can be stabilized by binding to the
      heptamer-octamer sequence in the immunoglobulin heavy-chain promoter. This
      correlates with cooperative DNA binding to this site. POU proteins from different
      subclasses, including Oct-1, Oct-2A, Oct-6, and a chimeric Oct-1 protein
      containing the Pit-1 POU domain, can bind cooperatively to a double binding site
      and form a heteromeric complex.

PMID- 1346338
TI  - Fatal familial insomnia, a prion disease with a mutation at codon 178 of the
      prion protein gene.
AB  - BACKGROUND: We previously described two members of a family affected by an
      apparently genetically determined fatal disease characterized clinically by
      progressive insomnia, dysautonomia, and motor signs and characterized
      pathologically by severe atrophy of the anterior ventral and mediodorsal thalamic
      nuclei. Five other family members who died of this disease, which we termed
      "fatal familial insomnia," had broader neuropathologic changes suggesting that
      fatal familial insomnia could be a prion disease. METHODS: We used antibodies to
      prion protein (PrP) to perform dot and Western blot analyses, with and without
      proteinase K, on brain tissue obtained at autopsy from two patients with fatal
      familial insomnia, three patients with sporadic Creutzfeldt-Jakob disease, and
      six control subjects. The coding region of the PrP gene was amplified and
      sequenced in the samples from the two patients with fatal familial insomnia.
      Restriction-enzyme analysis was carried out with amplified PrP DNA from 33
      members of the kindred. RESULTS: Protease-resistant PrP was found in both
      patients with fatal familial insomnia, but the size and number of protease
      resistant fragments differed from those in Creutzfeldt-Jakob disease. In the
      family with fatal familial insomnia, all 4 affected members and 11 of the 29
      unaffected members had a point mutation in PrP codon 178 that results in the
      substitution of asparagine for aspartic acid and elimination of the Tth111 I
      restriction site. Linkage analysis showed a close relation between the point
      mutation and the disease (maximal lod score, 3.4 when theta was zero).
      CONCLUSIONS: Fatal familial insomnia is a prion disease with a mutation in codon
      178 of the PrP gene, but the disease phenotype seems to differ from that of
      previously described kindreds with the same point mutation.

PMID- 1346339
TI  - Prion disease.

PMID- 1346340
TI  - The use of beta-agonists and the risk of death and near death from asthma.
AB  - BACKGROUND: Morbidity and mortality from asthma appear to be increasing, and it
      has been suggested that medications used to treat asthma are contributing to this
      trend. We investigated a possible association between death or near death from
      asthma and the regular use of beta 2-agonist bronchodilators. METHODS: Using
      linked health insurance data bases from Saskatchewan, Canada, we conducted a
      matched case-control study of subjects drawn from a cohort of 12,301 patients for
      whom asthma medications had been prescribed between 1978 and 1987. We matched 129
      case patients who had fatal or near-fatal asthma with 655 controls (who had
      received medications for asthma but had not had fatal or near-fatal events) with
      respect to region of residence, age, receipt of social assistance, and previous
      hospitalization for asthma. RESULTS: The use of beta-agonists administered by a
      metered-dose inhaler was associated with an increased risk of death from asthma
      (odds ratio, 2.6 per canister per month; 95 percent confidence interval, 1.7 to
      3.9) and of death or near death from asthma, considered together (odds ratio,
      1.9; 95 percent confidence interval, 1.6 to 2.4). For death from asthma, use of
      the beta-agonist fenoterol was associated with an odds ratio of 5.4 per canister,
      as compared with 2.4 for the beta-agonist albuterol. On a microgram-equivalent
      basis, the odds ratio for this outcome with fenoterol was 2.3, as compared with
      2.4 with albuterol. CONCLUSIONS: An increased risk of death or near death from
      asthma was associated with the regular use of inhaled beta 2-agonist
      bronchodilators, especially fenoterol. Regardless of whether beta-agonists are
      directly responsible for these adverse effects or are simply a marker for more
      severe asthma, heavy use of these agents should alert clinicians that it is
      necessary to reevaluate the patient's condition.

PMID- 1346341
TI  - The beta-agonist dilemma.

PMID- 1346342
TI  - [Anti-angina effect of amiodarone in therapy-resistant angina pectoris].
AB  - In a double-blind randomized trial 63 patients on the waiting list for coronary
      artery bypass grafting, with stable angina NYHA III and a positive stress test on
      triple (nitrates, beta- and calcium entry blockers) combination therapy, were
      studied for an additional antianginal effect of amiodarone over a period of 2
      months. In the treatment group an increase in exercise duration and a decrease of
      the double product and of ST-depression were noted. Thus, amiodarone is an
      effective antianginal agent in patients with limiting angina pectoris on
      conventional triple therapy.

PMID- 1346343
TI  - Role of testosterone in gamma-glutamyltranspeptidase-dependent renal
      methylmercury uptake in mice.
AB  - To elucidate the mechanisms responsible for sex and age differences in renal
      methylmercury uptake, effects of castration and testosterone treatment on mercury
      content and activity of renal gamma-glutamyltranspeptidase (gamma-GTP), which
      supposedly plays an important role in renal mercury uptake, were investigated in
      mice. Between 2 and 8 weeks of age, renal methylmercury uptake in male mice
      determined 4 hr after injection of a nontoxic dose of methylmercuric chloride
      (MMC, 1 mumol/kg, sc) increased about fivefold. At 4 weeks of age, a significant
      sex difference in renal mercury uptake first appeared. Renal mercury content in 4
      week-old male mice was twofold higher than that of females and increased with
      age, but remained constant in females. Small but significant (p less than 0.05)
      differences in mercury content in other tissues were observed, which could not
      account for the marked sex- and age-related differences in renal mercury
      concentrations. Renal gamma-GTP activity gradually increased in males with
      maturation, and a sexual dimorphism of renal gamma-GTP was apparent after the
      fourth week. Seven days after castration of 4-week-old male mice, both renal
      mercury content and gamma-GTP activity were decreased to the levels in females.
      Activity of gamma-GTP was subsequently elevated to control male levels by sc
      injection of testosterone (5 mg/kg/day x 7 days). In female mice, both renal
      mercury content and gamma-GTP activity were increased to the level of males by
      testosterone treatment (5 mg/kg/day x 14 days). Thus, the renal mercury content
      was closely correlated with changes in renal gamma-GTP activity. These results
      suggest that sex and age differences in renal methylmercury accumulation may be
      due to a difference in renal gamma-GTP activity controlled at least in part by
      testosterone.

PMID- 1346344
TI  - Inhibition of interleukin 2 receptor expression in normal human T cells by
      cyclosporine. Demonstration at the mRNA, protein, and functional levels.
AB  - In view of the importance of the IL-2 receptors in the expression of
      antiallograft immunity and the currently existing controversy regarding the
      effect of CsA on the induction of IL-2 receptors, we explored the effect of
      cyclosporine on the induction of interleukin-2 receptor alpha and beta in normal
      human T cells. The effect of CsA on the induction of IL-2 receptors was examined
      at the levels of mRNA expression (with the aid of the polymerase chain reaction),
      protein (by SDS-PAGE analysis of chemically crosslinked 125I-IL-2 membrane
      protein complexes and by FACS), and function (by Scatchard analysis of 125I-IL-2
      binding to T cells). The T cells were signaled with sn-1,2-dioctanoylglycerol and
      ionomycin or with crosslinked anti-CD3 and anti-CD2 mAbs. Our experimental design
      revealed that (A) CsA inhibits the induction of IL-2 receptor alpha and beta in
      normal human T cells, (B) the inhibitory activity is realized by a direct effect
      on T cells, and (C) the inhibitory activity is detectable at the pretranslational
      level--CsA significantly reduced the induction of mRNA encoding IL-2 receptor
      alpha and IL-2 receptor beta. These observations together persuasively
      demonstrate the ability of CsA to interrupt the emergence of IL-2 receptors on
      the surface of normal human T cells.

PMID- 1346345
TI  - Evidence that multiple defects in cell-surface molecule interactions across
      species differences are responsible for diminished xenogeneic T cell responses.
AB  - The purpose of the present study was to identify which of the several possible
      defects in cell-surface-molecule interactions are responsible for diminished
      mouse helper T cell responses to xenoantigens. We measured primary mouse anti
      monkey, anti-pig, and anti-human proliferation in vitro in experimental systems
      in which potential defects were partially corrected by lymphokine supplementation
      and/or the use of transgenic or hybridoma cell populations. We found that the
      diminished mouse helper T cell responses to xenoantigens result from at least two
      defects in cell-surface-molecule interactions between T cells and xenogeneic
      APCs, specifically TCR and/or CD8 interactions with xenogeneic class I MHC
      molecules and accessory molecule interactions with their ligands (probably LFA-1
      with ICAM-1/ICAM-2 and/or LFA-2 with LFA-3). Other investigators have identified
      additional defects, such as in lymphokine function across species differences.
      Thus, there appear to be multiple defects responsible for the diminished cellular
      immune response to xenoantigens.

PMID- 1346346
TI  - The importance of targeting the CD4+ T cell subset at the time of antigenic
      challenge for induction of prolonged vascularized allograft survival.

PMID- 1346347
TI  - Generation of H-2 class II-reactive CD8+ cells in mice after class II-disparate
      skin graft rejection.

PMID- 1346348
TI  - Mitochondrial DNA mutation and heteroplasmy in type I Leber hereditary optic
      neuropathy.
AB  - Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder
      characterized by bilateral acute or subacute loss of central vision, primarily in
      young males. A G----A single base mutation at 11778nt of the mitochondrial genome
      which eliminates a SfaNI restriction site [Wallace et al., 1988; Holt et al.,
      1989; Hotta et al., 1989; Singh et al., 1989; Vilkki et al., 1989; Yoneda et al.,
      1989; Stone et al., 1990; Lott et al., 1990.] has been found in more than 60% of
      the families with LHON studied. We studied 25 persons from 4 families with LHON
      using SfaNI and Mae III digestion of a 201 base pair polymerase chain reaction
      (PCR) product encompassing the 11778nt mutation. The loss of the SfaNI site and
      the acquisition of a Mae III site at 11778nt were identified in all maternal
      relatives of the LHON families studied. The mutation was heteroplasmic in all
      affected individuals, female carriers, and males at-risk. The heteroplasmy of
      mitochondrial DNA (mtDNA) was also identified by direct DNA sequencing of PCR
      amplified by direct DNA sequencing of PCR amplified mtDNA digested by SfaNI or
      Mae III. It appears that the proportion of the mutant mtDNA correlates with the
      severity of the disease.

PMID- 1346349
TI  - Five missense mutations at the adenosine deaminase locus (ADA) detected by
      altered restriction fragments and their frequency in ADA--patients with severe
      combined immunodeficiency (ADA-SCID).
AB  - Severe combined immunodeficiency (SCID) is a heterogeneous syndrome, due to X
      linked and autosomal recessive defects. A significant proportion of the autosomal
      recessive forms of SCID are due to mutations at the adenosine deaminase (ADA)
      locus. Nine different mutations at the ADA locus, including 7 missense point
      mutations, have been reported in children with ADA-SCID. We could detect 5 of the
      7 missense mutations associated with ADA-SCID by alterations in restriction
      fragments utilizing standard restriction digestion of genomic DNA and
      hybridization of radiolabelled ADA genomic probes to Southern transfers. We
      additionally developed more rapid nonradioactive methods employing digestion of
      genomic DNA amplified by PCR that also detected all 5 mutations. Using these
      methods, we have examined a sample of 45 ADA-SCID chromosomes and report that
      these 5 missense mutations account for one third of the ADA--chromosomes studied,
      with 2 mutations being relatively common.

PMID- 1346350
TI  - Rapid identification of deoxyribonucleic acid sequence differences in cytochrome
      P-450 21-hydroxylase (CYP21) genes with denaturing gradient gel blots.
AB  - Denaturing gradient gel electrophoresis was used to identify single-base
      differences in the cytochrome P-450 21-hydroxylase (CYP21) genes of 132 unrelated
      control individuals and family members of three unrelated patients with 21
      hydroxylase deficiency. The salt-wasting variety was caused by gene deletion and
      gene conversion/deletion mutations in affected members of two families studied.
      The simple virilizing form, present in the third family, was caused by an
      apparent point mutation not detectable by routine Southern blots. We have
      detected many restriction fragment melting polymorphisms in the CYP21 genes of
      the members of both salt-wasting families and normal individuals with denaturing
      gradient gel electrophoresis. We also identified a restriction fragment melting
      polymorphism specific for the simple virilizing patient in the third family. The
      data demonstrate that the CYP21 genes are highly polymorphic and that denaturing
      gradient gel electrophoresis is useful for genomic deoxyribonucleic acid analysis
      of patients with 21-hydroxylase deficiency.

PMID- 1346351
TI  - Exercise inhibits glucocorticoid-induced glutamine synthetase expression in red
      skeletal muscles.
AB  - One purpose of this study was to determine whether the suppression of
      glucocorticoid-induced glutamine synthetase (GS) gene expression by exercise is
      localized to fiber types that are known to be primarily recruited during
      endurance running. A second purpose examined whether denervation, which is
      associated with a reduction in contractile activity, would upregulate GS
      expression. Exercise consisted of treadmill running at 31 m/min for 12-16 wk.
      Glucocorticoid treatment (100 mg/kg body wt hydrocortisone 21-acetate) was
      administered during the last 11 days of the exercise program. Basal GS expression
      was lowest (GS enzyme activity, 43 +/- 3 nmol.h-1.mg protein-1; GS mRNA, 1.0
      arbitrary units) in the slow-twitch red soleus, a muscle type that is known to
      resist glucocorticoid-induced muscle wasting, intermediate (74 +/- 10 and 1.7 +/-
      0.2) in fast-twitch red quadriceps, a muscle type susceptible to atrophy, and
      highest (106 +/- 16 and 5.4 +/- 1.3) in fast-twitch white quadriceps, a muscle
      type known to be most susceptible to atrophy. Hormone treatment increased GS
      enzyme activity and mRNA by two- to fourfold in all muscle types. Exercise
      diminished GS enzyme activity and mRNA in the fast-twitch red fibers to 35-70% of
      sedentary control values in both basal and glucocorticoid-stimulated muscles. The
      running also reduced GS enzyme activity in hormone-treated slow-twitch fibers but
      did not alter basal or glucocorticoid-induced GS expression in fast-twitch white
      fibers. These results indicate that glucocorticoids induce similar relative GS
      expression across all muscle types, but the low absolute levels of expression in
      slow-twitch muscles are not related to any atrophy.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1346352
TI  - Mechanisms of cAMP-mediated relaxation of distal circular muscle in rabbit colon.
AB  - Photolytic release of free adenosine 3',5'-cyclic monophosphate (cAMP) from its
      caged form was used to evaluate the physiological role of several proposed
      mechanisms of cAMP-mediated relaxation of circular smooth muscle in the distal
      rabbit colon. Photolysis of caged cAMP produced a rapid relaxation of bethanechol
      contracted distal circular muscle strips that was dependent on ultraviolet
      exposure time. An increase in release of free cAMP, associated with increased
      ultraviolet exposure, was confirmed with high-performance liquid chromatography.
      Vanadate (an ATPase inhibitor) (3 mM) caused a 48% decrease in cAMP-mediated
      relaxation, while ouabain and a zero K+ bath solution failed to affect
      relaxation. cAMP-mediated relaxation of KCl-contracted strips was significantly
      less effective than that of bethanechol-contracted strips. Although this finding
      suggested that cAMP-mediated relaxation may involve K+ channel modulation,
      specific (glibenclamide, charybdotoxin) and nonspecific (TEA) K+ channel blockade
      failed to affect cAMP-mediated relaxation of bethanechol-contracted strips. The
      photolytic release of cAMP failed to relax Ca(2+)-contracted saponin skinned
      muscle strips. These studies suggest 1) modulation of Ca2+ pumps plays an
      important role in this model of relaxation of distal colonic circular muscle in
      the rabbit colon, 2) modulation of the Na+ pump or sarcolemmal K+ channels may
      not play an important physiological role in relaxation induced by a rapid rise in
      intracellular cAMP, and 3) cAMP does not seem to have a significant physiological
      effect on the Ca2+ sensitivity contractile apparatus.

PMID- 1346353
TI  - Intestinal acid inhibits gastric acid secretion by neural and hormonal mechanisms
      in rats.
AB  - To determine the relative contributions of neural reflexes and intestinal
      hormones to the inhibition of gastric acid secretion by intestinal acidification,
      rats with an extrinsically denervated, transplanted segment of jejunum, and those
      with an innervated segment of jejunum, were studied. Postoperatively, meal
      stimulated gastric acid secretion was measured. When the acid secretory response
      to intragastric liver extract reached a plateau, graded concentrations of
      hydrochloric acid or saline were instilled into the jejunal segments. Gastric
      acid secretion was inhibited by intrajejunal acid (pH 2.5) by 79% in the
      innervated rats and by 64% in the transplanted group. Thus at a pH of 2.5 there
      was a 15% greater maximum inhibition of plateau acid response in the innervated
      rats than in the transplanted rats, presumably because of the extrinsic neural
      contribution. To examine the hormonal mediators, the effects of a somatostatin
      monoclonal antibody and a CCK-A receptor antagonist (L 364718) on acid-induced
      inhibition of gastric acid secretion were studied in transplanted rats. Treatment
      with a somatostatin monoclonal antibody or with L 364718 reduced the acid-induced
      (pH 2.5) inhibition of gastric acid secretion by 93 and 27%, respectively.
      Jejunal acidification inhibits gastric acid secretion in the rat by both neural
      and hormonal mechanisms. The hormonal mechanism is mediated by somatostatin and
      CCK.

PMID- 1346354
TI  - Hemodynamic responses evoked by endothelin from central cardiovascular neural
      substrates.
AB  - Endothelin-1 (ET-1, 3-10 pmol) applied to the fourth cerebral ventricle of
      anesthetized ventilated rats decreased mean arterial pressure (MAP, 37 +/- 5 to
      55 +/- 5%), heart rate (13 +/- 7 to 21 +/- 3%), and renal blood flow (RBF, 41 +/-
      7 to 45 +/- 8%; all values are means +/- SE) for 30-90 min. At a 30-pmol dose of
      ET-1, the decrease in MAP was preceded by an increase (58 +/- 16%).
      Micropneumophoresis of ET-1 (100-300 fmol) into discrete glutamate-responsive
      cardiovascular loci within the nucleus tractus solitarii (NTS), viz., the dorsal
      strip and the commissural subnucleus, produced depressor and bradycardic
      responses. However, central ET-1 was ineffective in evoking swallowing responses
      when microinjected into glutamate-responsive deglutitive sites in the NTS. These
      data suggest that, at low doses, ET-1 evokes hypotension and bradycardia by a
      specific neuronal action in the central nervous system; one site of action
      appears to be the cardiovascular neural substrates within the NTS; decreases in
      RBF may be secondary to the hypotension, since renal vascular resistance also
      decreased. In anesthetized nonventilated rats, ET-1 (3 and 10 pmol) applied to
      the fourth ventricle produced profound respiratory depression accompanied by a
      transient pressor effect. Thus centrally administered ET-1 can elicit complex
      cardiovascular responses by a direct action on cardiovascular substrates and/or
      indirectly via respiratory depression.

PMID- 1346355
TI  - Halothane anesthesia abolishes pulmonary vascular responses to neural
      antagonists.
AB  - We investigated the effects of the inhalational anesthetic halothane on autonomic
      nervous system (ANS) regulation of the baseline pulmonary vascular pressure-flow
      (P/Q) relationship compared with that measured in the conscious state. Multipoint
      pulmonary vascular P/Q plots were constructed by stepwise constriction of the
      thoracic inferior vena cava to decrease venous return and Q. P/Q plots were
      generated in the same dogs in the conscious state and during halothane anesthesia
      (approximately 1.2% end tidal) in the intact (no drug) condition and after
      administration of selective ANS antagonists. In conscious dogs, sympathetic alpha
      1-adrenoreceptor block with prazosin decreased (P less than 0.01) the pulmonary
      vascular pressure gradient [pulmonary arterial pressure-pulmonary arterial wedge
      pressure (PAP-PAWP)] over the entire range of Q studied; i.e., inhibition of
      endogenous alpha 1-adrenoreceptor activity caused pulmonary vasodilation. In
      contrast, alpha 1-adrenoreceptor block had no effect on PAP-PAWP at any value of
      Q during halothane anesthesia. In conscious dogs, sympathetic beta-adrenoreceptor
      block with propranolol increased (P less than 0.01) PAP-PAWP over the entire
      range of Q studied; i.e., inhibition of endogenous beta-adrenoreceptor activity
      resulted in pulmonary vasoconstriction. However, beta-adrenoreceptor block had no
      effect on PAP-PAWP at any value of Q during halothane anesthesia. Finally,
      cholinergic receptor block with atropine decreased (P less than 0.05) PAP-PAWP at
      values of Q greater than 100 ml.min-1.kg-1 in conscious dogs but had no effect on
      PAP-PAWP at any value of Q during halothane anesthesia. These results indicate
      that endogenous ANS regulation of the baseline pulmonary vascular P/Q
      relationship observed in conscious dogs is abolished during halothane anesthesia.

PMID- 1346356
TI  - Beta 2-adrenoceptor-mediated positive dromotropic effects on atrioventricular
      node of dogs.
AB  - The functional significance of beta 2-adrenoceptors in atrioventricular (AV)
      nodal conduction was investigated by using canine isolated blood-perfused AV node
      preparations. Dose-dependent shortening of the atrio-His bundle (A-H) interval by
      dl-procaterol hydrochloride hemihydrate (0.03-1 nmol) injected intra-arterially
      into the AV node artery was affected little by an infusion of dl-atenolol (10
      nmol/min) into the same artery, whereas the dose-response curve for the positive
      dromotropic effect of procaterol was shifted markedly to the right by
      approximately 1.5 and 2.5 log units with ICI 118551 [erythro-dl-1-(7-methylindan
      4-yloxy)-3-isopropylamino-bu tan-2-ol]- hydrochloride (1 and 10 nmol/min). The
      positive dromotropic effect of dl-T-1583 [alpha-(3,4,5
      trimethoxyphenethylaminomethyl)-3,4-dihydroxybenzyl- alcohol] hydrochloride (30
      300 pmol), a selective beta 1-adrenoceptor agonist, was shifted to the right by
      approximately 1.2 log units with dl-atenolol (10 nmol/min) but was affected
      little by ICI 118551 (10 nmol/min). The dose-response curve for l-isoproterenol
      hydrochloride (3-100 pmol) was shifted to the right by 0.7 log unit with ICI
      118551 (10 nmol/min) and by 1.7 log units with atenolol (10 nmol/min). The dose
      response curve for dl-norepinephrine (0.03-1 nmol) was shifted to the right by
      1.0 log unit with atenolol only, whereas the curve for l-epinephrine (0.03-1
      nmol) was shifted by 0.45 log unit with ICI 118551 (10 nmol/min). These results
      suggest that both beta 1- and beta 2-adrenoceptors, which coexist on the AV node,
      play a functional role in AV nodal conduction.

PMID- 1346357
TI  - Fluid restitution and shift of blood volume in anesthetized rabbits subject to
      cyclic hemorrhage.
AB  - We investigated the effect of a 10% cyclic blood volume change with a period of 2
      or 4 min to study the short-term control of blood volume. In experiments with
      pentobarbital-anesthetized rabbits, the blood density variation over a 2-min
      cycle is 0.94 +/- 0.04 (SE) g/l, and the plasma density variation is 0.17 +/-
      0.04 g/l. The plasma density variation could result from a fluid restitution from
      the extravascular space (with a density 1,005 g/l), with a volume equal to 14% of
      the withdrawn blood volume. This restitution cannot account, however, for the
      entire observed density change in arterial blood. Because of the Fahraeus effect
      in microvascular flow, a shift in blood volume from the microvasculature is
      another mechanism that could lead to a decrease in the density of arterial blood.
      An analysis of the blood and plasma density variations indicates that a blood
      volume (49% of the shed volume) is shifted from the micro- to macrocirculation.
      This volume compensation by fluid restitution and volume shift acts to minimize
      the effect of hemorrhage on the filling of the venous system. We found that the
      blood density waveform parallels the change in blood volume. When the blood
      volume change reverses its direction, the density change also reverses direction
      with a time delay less than 8 s. The blood density variations are not altered by
      bilateral vagotomy or its combination with hexamethonium (a sympathetic
      ganglionic blocker). These observations of anesthetized rabbits indicate that the
      short-term compensation is primarily due to the volume shift from the
      microcirculation and is not regulated by humoral or neural mechanisms but by
      local mechanisms such as autoregulation and the passive response due to changes
      in microvascular pressure.

PMID- 1346358
TI  - Myocardial oxygenation in the isolated working rabbit heart as a function of
      work.
AB  - Myocardial O2 consumption (MVO2) was stimulated up to two-fold by either
      increasing afterload or beta-receptor stimulation in working normothermic
      isolated rabbit hearts while noninvasively monitoring the O2 delivery or
      phosphate compounds (total n = 48). Intracellular O2 delivery was estimated with
      the use of myocardial optical absorbance changes centered at 603.5 and 582 nm
      that correlate with cytochrome aa3 redox and myoglobin oxygenation states.
      Phosphate-containing metabolites (ATP, phosphocreatine, free ADP) were assessed
      using 31P nuclear magnetic resonance spectroscopy. Measurements were made both
      with intact autoregulation and after maximal vasodilation by 1 microM
      nitroprusside (NP). When afterload was used to increase MVO2, absorbance
      decreased at 603.5 nm and increased at 582 nm, consistent with a 10-15% increase
      in myocardial oxygenation, without an associated change in cardiac phosphate
      compounds. NP caused a further increase in myocardial oxygenation and venous PO2
      consistent with an increase in the O2 supply-to-demand ratio. Increases in MVO2
      due to beta-stimulation alone were not associated with changes in 603.5-nm
      absorbance or phosphate compounds, but in combination with NP were accompanied by
      increased oxygenation, venous PO2, and cardiac phosphocreatine. KCl arrest caused
      maximal increases in oxygenation and phosphocreatine. These findings suggest that
      neither cytochrome aa3 nor myoglobin in the isolated working rabbit heart is
      fully oxidized or oxygenated, respectively. Furthermore, the oxygenation state of
      the tissue varied both with afterload-induced changes in cardiac work and with
      changes in O2 supply/demand.

PMID- 1346359
TI  - True histiocytic malignancy associated with a malignant teratoma in a patient
      with 46XY gonadal dysgenesis.
AB  - The relatively frequent association of hematologic neoplasia and primary
      mediastinal germ cell tumors has been reported. Of these hematologic
      malignancies, nine were classified as malignant histiocytosis or acute
      monoblastic leukemia, and all occurred in males. We now report on a patient who
      was phenotypically female, with 46XY gonadal dysgenesis, and who developed a true
      histiocytic malignancy that presented as a large hepatic tumor and also involved
      the spleen, right kidney, and lymph nodes. Twenty-six months before the
      development of the histiocytic malignancy, an ovarian malignant teratoma with
      yolk sac elements was removed; the patient subsequently received chemotherapy.
      The neoplasm was composed of large pleomorphic cells and the histiocytic nature
      was established by cytologic, cytochemical, immunologic, and ultrastructural
      studies. In the course of her illness, the patient developed classic acute
      monoblastic leukemia 8 months after the diagnosis of histiocytic malignancy.
      Karyotypic analysis of the hepatic tumor, bone marrow, and blood showed 46XY
      gonadal dysgenesis. We believe that this is the first reported case of a
      phenotypically female patient who developed these two rare malignancies. It
      suggests that the association between germ cell tumors and histiocytic malignancy
      in genotypically male individuals may not be coincidental or secondary to
      therapy, but may be a phenomenon related to dysgenetic gonads in the presence of
      a Y chromosome.

PMID- 1346360
TI  - Inhibition of DNA synthesis by somatostatin in rat hepatocytes stimulated by
      hepatocyte growth factor or epidermal growth factor.
AB  - The antiproliferative effects of somatostatin on hepatocytes stimulated by
      hepatocyte growth factor (HGF) or epidermal growth factor (EGF) were investigated
      using primary cultures of adult rat hepatocytes. Somatostatin inhibits HGF
      induced (at a dose of 10 ng/mL) or EGF-induced (at a dose of 100 ng/mL) 3H
      thymidine incorporation into hepatocytes in a dose-dependent manner (10(-10) to
      10(-8) M). This inhibition was confirmed by autoradiography. The effect of
      somatostatin was nontoxic as judged by preserved albumin synthesis, a marker for
      differentiated hepatocyte function. In the presence or absence of somatostatin,
      neither HGF nor EGF significantly altered intracellular cyclic adenosine
      monophosphate (cAMP). We conclude that somatostatin is a potent inhibitor of HGF-
      or EGF-induced deoxyribonucleic acid synthesis in adult rat hepatocytes. The
      mechanism of this inhibition appears to be independent of cAMP. The significance
      of somatostatin in liver regeneration has yet to be assessed.

PMID- 1346362
TI  - Somatostatin stimulation of the normal esophagus.
AB  - The inhibitory effects of somatostatin on gastric and small bowel motor function
      are well documented. However, the effects of somatostatin on esophageal body
      motility and lower esophageal sphincter tone are not completely defined. We
      investigated the effects of octreotide, a long-acting somatostatin analogue, on
      the esophageal body and the lower esophageal sphincter in 15 healthy volunteers.
      Lower esophageal sphincter tone was increased by octreotide infusion. Esophageal
      body contraction amplitude and velocity were also increased by octreotide
      infusion. Our data show that somatostatin stimulates the normal human esophagus,
      an action mediated either by a direct effect, a central nervous system action, or
      the inhibition of the secretion of gastrointestinal hormones that influence
      esophageal motor activity.

PMID- 1346361
TI  - Platelet activating factor-induced changes in gastric motility and vascular
      resistance.
AB  - Our study evaluated the hypothesis that gastric contractions may contribute to
      ischemia by increasing vascular resistance. Using an ex vivo segment of the dog's
      stomach as the experimental model, contractions were induced with platelet
      activating factor (PAF) and bethanechol, a cholinergic vasodilator. Spontaneous
      contractions produced slight increases in luminal pressure and corresponding
      increases in vascular resistance. PAF caused statistically significant, dose
      dependent increases in the force of gastric contractions that were highly
      correlated with phasic changes in vascular resistance. To ensure that the
      relationship between contractions and vascular resistance was independent of
      vascular tone, we next examined responses to bethanechol. Bethanechol stimulated
      contractions that also transiently increased both luminal pressure and vascular
      resistance. Our results demonstrate that gastric contractions markedly increase
      vascular resistance and support the hypothesis that hypercontractility may
      contribute to the development of mucosal ischemia during ulceration.

PMID- 1346363
TI  - Ovarian strumal carcinoid in association with multiple endocrine neoplasia, type
      IIA.
AB  - Strumal carcinoid is an unusual form of monodermal ovarian teratoma with thyroid
      like follicles admixed with typical carcinoid tumor patterns. We encountered a
      case of this neoplasm in a patient with multiple endocrine neoplasia, type IIA
      (Sipple's syndrome), including a medullary thyroid carcinoma diagnosed 24 years
      previously. During evaluation of bilateral adrenal pheochromocytomas, a
      unilateral left ovarian strumal carcinoid was discovered. Subsequently, the
      patient had a parathyroid adenoma excised. The ovarian tumor was
      immunohistochemically reactive for neuron-specific enolase, chromogranin,
      synaptophysin, and serotonin, but did not stain for calcitonin. The follicular
      structures stained for thyroglobulin. This unusual case shows that ovarian
      strumal carcinoid, like carcinoid tumors at other sites, may arise in association
      with multiple endocrine neoplasia.

PMID- 1346364
TI  - Prenatal ethanol exposure during the last third of gestation in rat reduces
      hippocampal NMDA agonist binding site density in 45-day-old offspring.
AB  - The effect of ethanol exposure during different periods of prenatal or postnatal
      development on hippocampal N-methyl-D-aspartate (NMDA) receptor binding was
      studied in rat. Fetal rat pups were exposed to ethanol for different periods of
      time during gestation via maternal consumption of a 3.35% ethanol liquid diet. In
      a separate experiment, neonatal pups were fed 2.51 g ethanol/kg body weight/day
      from Postnatal Day (PD) 4 to PD 10 via intragastric feeding tube. These two
      ethanol administration paradigms produced average peak maternal and pup blood
      ethanol concentrations of 39 mg/dl and 57 mg/dl, respectively. At 45 days of age,
      offspring from each treatment group were sacrificed for measurements of
      hippocampal NMDA-sensitive [3H]-glutamate binding site density using in vitro
      radiohistochemical techniques. As observed previously, prenatal ethanol exposure
      throughout gestation resulted in NMDA-sensitive [3H]-glutamate binding site
      reductions in the apical dendritic field regions of dentate gyrus, hippocampal
      CA1 and subiculum of dorsal hippocampal formation compared to the ad lib or pair
      fed control groups. NMDA-sensitive [3H]-glutamate binding was not different than
      control in rats exposed to ethanol during the first half of gestation only.
      Prenatal ethanol exposure during the last half or the last third of gestation
      resulted in NMDA-sensitive [3H]-glutamate binding site reductions comparable to
      the binding site reductions observed in rats exposed to ethanol throughout
      gestation. Hippocampal NMDA-sensitive [3H]-glutamate binding site density in
      postnatal ethanol-exposed rats was not different than the suckling or gastrostomy
      control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346365
TI  - SDZ 280-446, a novel semi-synthetic cyclopeptolide: in vitro and in vivo
      circumvention of the P-glycoprotein-mediated tumour cell multidrug resistance.
AB  - SDZ 280-446 is a semi-synthetic derivative of a natural cyclic peptolide. Its
      ability to sensitise in vitro tumour cells whose resistance is due to P
      glycoprotein-mediated anticancer-drug efflux was shown using four different pairs
      of parental drug-sensitive (Par-) and multidrug-resistant (MDR-) cell lines, from
      three different species (mouse, human, Chinese hamster) representing four
      different cell lineages (monocytic leukaemia, nasopharyngeal epithelial
      carcinoma, colon epithelial carcinoma, ovary fibroblastoid carcinoma), and using
      four different drug classes (colchicine, vincristine, daunomycin/doxorubicin and
      etoposide). By measuring its capacity to restore normal drug sensitivity of MDR
      cells in culture in vitro, it appeared that SDZ 280-446 belongs to the same class
      of very potent chemosensitisers as the cyclosporin derivative SDZ PSC 833: both
      are about one order of magnitude more active than cyclosporin A (CsA), which is
      itself about one order of magnitude more active than other known chemosensitisers
      (including verapamil, quinidine and amiodarone which have already entered
      clinical trials in MDR reversal). Low concentrations of SDZ 280-446 could also
      restore cellular daunomycin retention in MDR-P388 cells to the levels found in
      the Par-P388 cells. SDZ 280-446 was also effective as a chemosensitiser when
      given orally in vivo. In a syngeneic mouse model, combined therapy with vinca
      alkaloids given i.p. and SDZ 280-446 given per os for 5 consecutive days
      significantly prolonged the survival of MDR-P388 tumour-bearing mice, when
      compared with mice receiving vinca alkaloids alone. Another protocol, using three
      cycles of i.p. doxorubicin at 4 day intervals, could also not increase MDR-P388
      tumour-bearing mouse survival unless the mice received SDZ 280-446 orally 4 h
      before each doxorubicin injection. Though only very few combined therapy
      treatment protocols have been tested so far, clear increases in survival time of
      MDR-tumour-bearing mice were regularly obtained, leaving hope for major
      improvement of the therapy using other dosing schedules.

PMID- 1346366
TI  - Relationship between c-erbB-2 protein product expression and response to
      endocrine therapy in advanced breast cancer.
AB  - Of 221 patients with breast cancer of known epidermal growth factor receptor
      (EGFR) and oestrogen receptor (ER) status, 99 had developed recurrences during
      the period of follow-up (range 3-60 months, median 24 months). Of these, 72
      received endocrine therapy as first-line treatment for relapse.
      Immunohistochemical assessment of c-erbB-2 protein product expression was made
      using paraffin-embedded tumour tissue from 65 of these 72 patients. Including
      patients whose disease remained stable for more than 6 months with those showing
      an objective response (CR or PR for more than 3 months), only one (7%) of 14 c
      erbB-2 positive tumours responded to endocrine manipulation compared with 19
      (37%) of 51 c-erbB-2 negative tumours (P less than 0.05). Coexpression of c-erbB
      2 reduced the response rate of ER positive patients from 48% to 20% and of ER
      negative cases from 27% to 0% (P less than 0.01). EGFR and c-erbB-2 protein
      appeared to have additive effects in reducing the likelihood of response, and
      none of eight patients with EGFR positive, c-erbB-2 positive tumours derived
      benefit from endocrine therapy. The results of this study suggest that c-erbB-2
      protein overexpression, a marker of poor prognosis in breast cancer, is
      associated with a lack of response to endocrine therapy on relapse, and
      particularly in combination with EGFR may be useful in directing therapeutic
      choices.

PMID- 1346367
TI  - Boundaries and fields in early embryos.

PMID- 1346368
TI  - Homeobox genes and axial patterning.

PMID- 1346369
TI  - Effects of interferon-alpha on human B cell responsiveness: biphasic effects in
      cultures stimulated with Staphylococcus aureus.
AB  - Although interferon-alpha (IFN-alpha) has been found to be involved in the immune
      regulation in vivo, the effects of IFN-alpha on human B cells have not yet been
      clarified because of conflicting results in the literature. The present study
      therefore examined the effects of several subtypes of IFN-alpha (natural, alpha
      1, alpha 2a, alpha 2b) on B cell responsiveness in detail by comparing different
      experimental conditions. Highly purified B cells from normal human individuals
      were cultured with Staphylococcus aureus (SA) + IL-2 or with immobilized anti-CD3
      activated T4 cells in the presence or absence of IFN-alpha. IFN-alpha enhanced
      the immunoglobulin (Ig) production induced by immobilized anti-CD3-activated T4
      cells. By contrast, IFN-alpha (5-50,000 IU/ml) suppressed the Ig production
      induced by SA + IL-2. The suppression by IFN-alpha was dependent on the
      concentration of SA. The inhibitory effects of IFN-alpha in SA-stimulated
      cultures were exerted in the first 72 hr of cultures and required the presence of
      IL-2, whereas IFN-alpha enhanced the maturation of B cells when it was added
      after 72 hr of cultures. The suppressive effects of IFN-alpha were overcome by
      addition of immobilized anti-CD3-preactivated T cells that had been treated with
      mitomycin C, but not by the addition of fresh T cells or soluble factors produced
      by activated T cells. Of interest, IFN-alpha did not inhibit the expression of IL
      2R, but inhibited that of intercellular adhesion molecule-1 (ICAM-1) on B cells
      after stimulation with SA + IL-2, suggesting that the suppressive effects of IFN
      alpha might be related to the regulation of B cell-B cell contacts through ICAM
      1. There was no significant difference in effects on B cells among various
      subtypes of IFN-alpha. These results suggest that the effects of IFN-alpha on
      human B cell responsiveness may be different depending on the nature of
      stimulation. Moreover, the data indicate that IFN-alpha enhances the
      differentiation of activated B cells irrespective of the activation signals.

PMID- 1346370
TI  - Modification by ketamine on the neuromuscular actions of magnesium, vecuronium,
      pancuronium and alpha-bungarotoxin in the primate.
AB  - The neuromuscular effects of ketamine, at cumulative doses of 2.5 and 10 mg.kg-1
      iv, were studied by electromyographically quantifying the thumb response evoked
      by ulnar nerve stimulation in 25 monkeys anaesthetized with pentobarbital-N2O-O2.
      Ketamine alone at these doses had no neuromuscular effects. When the EMG response
      was maintained at 50% of control by a continuous infusion of magnesium,
      vecuronium, or pancuronium, ketamine depressed the responses by an additional 13
      +/- 3%, 34 +/- 7% and 32.5 +/- 3.3% (mean +/- SEM), respectively, at the highest
      dose, P less than 0.05. In contrast, ketamine had no effect on the neuromuscular
      block produced by incremental doses of alpha-bungarotoxin. These results indicate
      that ketamine does not act on the postjunctional acetylcholine receptor. It plays
      a secondary role in neuromuscular block, possibly by prejunctional or
      postjunctional effects independent of receptor occupation.

PMID- 1346371
TI  - Esmolol prevents and suppresses arrhythmias during halothane anaesthesia in dogs.
AB  - The antiarrhythmic effect of esmolol, a selective beta 1 adrenoreceptor blocker,
      was evaluated in the presence of epinephrine induced arrhythmias in dogs (n = 6).
      The arrhythmogenic dose of epinephrine (ADE) during 1.2 MAC halothane in dogs was
      increased from 3.23 +/- 0.25 (mean +/- SD) to 30.90 +/- 3.56 micrograms.kg-1.min
      1 (P less than 0.001) by the prior administration of esmolol 0.5 microgram.kg-1
      bolus followed by an infusion at the rate of 150 micrograms.kg-1.min-1. Higher
      esmolol infusion doses of 200 micrograms.kg-1.min-1 further increased ADE to 99.0
      +/- 2.92 micrograms.kg-1.min-1 (P less than 0.001). After discontinuation of
      esmolol and during continued halothane anaesthesia, ventricular tachycardia was
      induced by increasing the infusion rate of the 100 micrograms.ml-1 solution of
      epinephrine. In all dogs ventricular tachycardia was restored to sinus rhythm by
      a bolus dose of esmolol (1 microgram.kg-1). We conclude that esmolol pretreatment
      increases the ADE during halothane anaesthesia in dogs. Our data suggest that
      esmolol may be useful as an antiarrhythmic agent in the management of epinephrine
      related ventricular arrhythmias during anaesthesia in man.

PMID- 1346372
TI  - Expression of P-glycoprotein gene in marine sponges. Identification and
      characterization of the 125 kDa drug-binding glycoprotein.
AB  - In the present paper it is shown that the marine sponges Geodia cydonium and
      Verongia aerophoba contain the gene coding for P-glycoprotein P170, also known as
      a multidrug-resistance gene. Western blot studies revealed that polyclonal
      antibodies raised against hamster P170 cross-react with the sponge polypeptide of
      Mr 125,000. After endoglycosidase F treatment, the sponge P125 is converted to a
      polypeptide of Mr 105,000. Northern blot studies, using the human P170 cDNA
      probe, revealed a size of 4.2 kb for the sponge P125 transcript. The level of
      this transcript does not change in response to incubation with the aggregation
      factor. Confocal laser scanning microscopy showed that P125 is a cell membrane
      bound protein. In addition, sponge membrane vesicles possess a potential to bind
      in vitro 2-acetylamino-fluorene, vincristine and daunomycin. This process is
      Verapamil-sensitive, a characteristic known also for the mammalian vesicle
      associated P170. The data reported demonstrate that the classical multidrug
      resistance mechanism, described in drug-resistant tumor cell lines, functions
      also in sponges and may explain the relative resistance of these animals to
      pollution.

PMID- 1346373
TI  - Potent inhibition of aflatoxin-induced hepatic tumorigenesis by the
      monofunctional enzyme inducer 1,2-dithiole-3-thione.
AB  - 1,2-Dithiole-3-thiones are five-membered cyclic sulfur-containing compounds with
      antioxidant, chemotherapeutic, radioprotective and chemoprotective properties.
      Several substituted 1,2-dithiole-3-thiones are used medicinally and one of these,
      oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione], has been recently
      shown to be an inhibitor of aflatoxin B1 (AFB1) hepatocarcinogenesis in the rat.
      Structure-activity studies have been undertaken to probe the mechanisms by which
      dithiolethiones inhibit carcinogenesis. Such studies revealed that unsubstituted
      1,2-dithiole-3-thione was more effective than oltipraz at inhibiting aflatoxin
      DNA adduct formation in vivo and at inducing electrophile detoxication enzymes in
      cell culture. In the present studies the effects of dietary administration of 1,2
      dithiole-3-thione on the induction of xenobiotic metabolizing enzymes and
      inhibition of aflatoxin-induced hepatic tumorigenesis were examined. Male F344
      rats were fed graded doses of 1,2-dithiole-3-thione (0.001-0.03%) for 4 weeks.
      During the second and third weeks of 1,2-dithiole-3-thione feeding, rats were
      dosed by gavage with 250 micrograms of AFB1/kg five times a week. Rats were then
      restored to control AIN-76A diet 1 week after cessation of AFB1 dosing. At 4
      months, focal areas of hepatocellular alteration were identified and quantified
      by staining sections of liver for gamma-glutamyltranspeptidase (GGT) activity and
      glutathione S-transferase P (GST-P) expression. Treatment with 1,2-dithiole-3
      thione at the lowest dose (0.001%) reduced by greater than 80% the volume of
      liver occupied by GGT or GST-P foci; higher dietary concentrations provided
      greater than 98% reductions in the volume per cent of these markers for
      presumptive preneoplastic lesions. All dietary concentrations of 1,2-dithiole-3
      thione resulted in significant elevations in hepatic GST activities. In accord
      with the protective effects against tumorigenesis, 4- to 6-fold increases in the
      specific activities of aflatoxin-glutathione conjugation were observed in
      cytosols prepared from livers of animals fed 1,2-dithiole-3-thione. By contrast,
      1,2-dithiole-3-thione did not have any detectable inductive effects on hepatic
      microsomal cytochrome P450 levels or activities. Dietary administration of 1,2
      dithiole-3-thione also elevated activities of GSTs and other phase II enzymes in
      several extrahepatic organs. This broad pattern of induction of detoxication
      enzymes by 1,2-dithiole-3-thione supports the potential widespread use of this
      compound as a protective agent against chemical carcinogenesis and other forms of
      electrophile toxicity.

PMID- 1346374
TI  - Induction of intercellular adhesion molecule-1 (CD54) on human hepatoma cell line
      HepG2: influence of cytokines and hepatitis B virus-DNA transfection.
AB  - Human hepatocyte expression of intercellular adhesion molecule-1 (ICAM-1) (CD54)
      was studied in vitro by exposing the well differentiated human hepatoblastoma
      cell line HepG2 to various cytokines. In addition, hepatitis B virus (HBV)-DNA
      transfected HepG2 cells were also analysed. Expression of ICAM-1 on HepG2 cells
      was then revealed with an immunohistochemical procedure. Untreated HepG2 cells
      were unreactive, but showed strong cytoplasmic ICAM-1 immunoreactivity after
      treatment with interferon-gamma (IFN-gamma). This induction was completely
      inhibited by addition of a neutralizing antibody directed to IFN-gamma. IL-1, IL
      6, tumour necrosis factor-alpha (TNF-alpha) and IFN-alpha, used alone or in
      combination, did not induce ICAM-1 expression, neither did they inhibit the IFN
      gamma-induced expression of this adhesion molecule on HepG2 cells. Untreated
      hepatitis B virus-DNA transfected HepG2 cells expressed membranous ICAM-1. These
      results indicate that IFN-gamma is the main cytokine trigger for ICAM-1
      expression on HepG2 cells, suggesting that in areas of liver inflammation this
      adhesion molecule is up-regulated on hepatocytes by locally released IFN-gamma.
      In addition, expression of ICAM-1 by hepatitis B virus-DNA transfected HepG2
      cells suggests other, still unknown, triggering mechanisms in the induction of
      such adhesion molecules, for instance gene activation by viral genome, or
      autocrine virus-induced hepatocellular cytokine production.

PMID- 1346375
TI  - Therapeutic response to somatostatin analogue, BIM 23014, in metastatic prostatic
      cancer.
AB  - Metastatic prostate cancer is well known to respond to hormonal manipulations,
      but once progression occurs new treatment modalities are required. Specific and
      systemic antitumour therapy is preferable to local treatments such as
      radiotherapy in such patients. The finding that somatostatin analogue, BIM 23014,
      inhibits prostatic tumour growth in animal models is of great interest. We
      treated 25 poor risk patients with progressive metastatic prostate cancer.
      Sixteen had also failed to respond to 'total androgen blockade'. Two patients
      have achieved a partial remission, one of which is maintained at over 30 months,
      and three had stable disease for over 6 months. Side effects have consisted of
      mild diarrhoea and abdominal cramp in the first few days of treatment in a
      minority of the patients. These results are encouraging and further randomized
      studies are in progress.

PMID- 1346376
TI  - Localization of the rat insulin I gene (INS1) to chromosome 1q55 by fluorescence
      in situ hybridization.
AB  - The rat insulin I gene (INS1) was assigned to chromosome 1q55 using fluorescent
      in situ hybridization. In addition, several RFLPs were detected among 11 inbred
      rat strains.

PMID- 1346377
TI  - [Doxazosin-induced lupus erythematodes].

PMID- 1346378
TI  - Gamma-aminobutyric acid-glutamate interaction in the control of somatostatin
      release from hypothalamic neurons in primary culture: in vivo corroboration.
AB  - Recent studies have provided new data on the neuroendocrine role of glutamate
      (the major excitatory neurotransmitter) on somatostatin release. The
      neuroendocrine role of gamma-aminobutyric acid (GABA) (the major inhibitory
      neurotransmitter) on this same secretion, is also well established. Our objective
      was thus to investigate whether GABA and glutamate, which have opposite
      neurotransmission signals, could interact in the control of hypothalamic
      somatostatin release. Pharmacological manipulations of the two types of receptors
      were performed in vitro on primary cultures of hypothalamic neurons secreting
      somatostatin. We found that tonic release of somatostatin was reduced by 76% in
      the presence of tetrodotoxin (TTX) and was regulated by endogenous secretion of
      glutamate and GABA. CGS 19755, a highly selective N-methyl-D-aspartate (NMDA)
      receptor antagonist, significantly reduced tonic somatostatin secretion whereas
      it was strongly increased by picrotoxin and bicuculline, two GABAA antagonists.
      When CGS 19755 was applied with picrotoxin, somatostatin release was the same as
      levels obtained in the control group with TTX. GABA reduced tonic somatostatin
      release (in the presence or absence of TTX), and glutamate-stimulated secretion
      in a dose-dependent manner. Picrotoxin stimulation of tonic somatostatin release
      was additive with that obtained after glutamate stimulation and was also dose
      dependent. This interaction was also studied in vivo in unanesthetized rats
      bearing a push-pull cannula stereotaxically implanted into the median eminence.
      Ip injected CGS 19755 (an antagonist that can freely permeate the blood-brain
      barrier) completely blocked the peak secretion of somatostatin observed after ip
      picrotoxin administration, whereas there was no significant effect when it was
      injected alone. These findings corroborated our in vitro data and allow us to
      postulate that GABA and glutamate interact in the control of somatostatin.

PMID- 1346379
TI  - Time course and mechanism of growth hormone's negative feedback effect on its own
      spontaneous release.
AB  - Endogenous pulsatile GH secretion is blunted by the administration of exogenous
      GH; however, few data are available on the time course of GH negative feedback,
      and the mechanism by which this occurs still remains unclear. In the present
      study, we examined the temporal pattern of the inhibitory effect induced by an
      acute (single) and chronic (5 days) sc recombinant human (rh) GH injection
      regimen on spontaneous GH release in the rat and assessed the possible
      involvement of the hypothalamic GH-inhibitory peptide, somatostatin (SRIF), in
      this response. Eight-hour (0800-1600 h) GH secretory profiles, obtained from free
      moving adult male rats administered a single sc injection of 200 micrograms rhGH
      at 0800 h, revealed a marked suppression of spontaneous GH pulses (GH peak
      amplitude: 45.7 +/- 10.9 vs. 207.8 +/- 31.7 ng/ml in H2O-injected control rats; P
      less than 0.001) lasting for up to 4.1 +/- 0.1 h after the injection (mean 4-h
      plasma GH level: 13.6 +/- 3.6 vs. 49.4 +/- 7.0 ng/ml in H2O-injected controls; P
      less than 0.01). During the subsequent 4- to 8-h period, recovery of spontaneous
      GH secretory bursts was evident, and neither the GH peak amplitude nor mean 4-h
      plasma GH level of rhGH-treated rats was significantly different from that of H2O
      injected controls. The magnitude, time course, and recovery of the rhGH-induced
      inhibitory effect on pulsatile GH release after chronic rhGH treatment was
      similar to that after a single injection. Passive immunization of rhGH-treated
      rats with SRIF antiserum reversed the rhGH-induced inhibition of spontaneous GH
      pulses (peak amplitude: 131.7 +/- 53.7 vs. 7.1 +/- 3.4 ng/ml in rhGH-treated
      control rats given normal sheep serum; P less than 0.05) and restored both the GH
      peak amplitude and mean plasma GH level to values similar to those in H2O
      injected controls. Taken together, these results demonstrate that: 1) the
      inhibitory effect of rhGH on endogenous pulsatile GH release is of short duration
      (approximately 4 h); 2) the time course of this response does not change after 5
      day repeated rhGH administration; and 3) the feedback effect of GH on its own
      spontaneous release is exerted, at least in part, by increasing hypothalamic SRIF
      secretion. Such a mechanism of GH feedback may be important in the physiological
      control of pulsatile GH secretion.

PMID- 1346380
TI  - Developmentally regulated polyadenylation of two discrete messenger ribonucleic
      acids for mullerian inhibiting substance.
AB  - Mullerian inhibiting substance (MIS) is a 140-kilodalton homodimeric glycoprotein
      that causes regression of the Mullerian ducts in male embryos, and may also have
      a role in both males and females in the regulation of germ cell maturation. We
      examined the ontogeny of MIS messenger RNA (mRNA) in rat testes from midgestation
      through adulthood and found two discrete MIS mRNA species that are
      developmentally regulated. The larger 2.0-kilobase species is abundant at
      embryonic day 14, then decreases in late gestation, and is barely detectable
      after birth. The smaller 1.8-kilobase species is first noted at embryonic day 18
      and is the major species detected postnatally. Both species are abundant just
      prior to birth, at embryonic day 21, then decrease markedly after birth. This
      variation in MIS mRNA levels correlates with the developmental expression of MIS
      protein. A series of oligonucleotide-directed ribonuclease H mapping experiments
      determined that the two mRNA species differ at their 3' ends in the extent of
      polyadenylation. Thus, differential polyadenylation of MIS mRNA may be an
      additional mechanism for regulating MIS expression during fetal and postnatal
      development.

PMID- 1346381
TI  - Pituitary adenylate cyclase activating polypeptide, growth hormone (GH)-releasing
      peptide and GH-releasing hormone stimulate GH release through distinct pituitary
      receptors.
AB  - GH secretion has been thought traditionally to be regulated by the two
      hypothalamic hormones, GH-releasing hormone (GHRH) and somatostatin (SRIF).
      Recent evidence has suggested that other factors may be involved. These factors
      include the natural ligand for the synthetic hexapeptide GH-releasing peptide
      (GHRP) and the putative hypophysiotropic factor pituitary adenylate cyclase
      activating polypeptide (PA-CAP). Accordingly, we examined the effects of GHRP and
      PACAP on GH secretion at the single cell level using the reverse hemolytic plaque
      assay which allows distinction of effects on the number of secreting cells and
      the amount of hormone each cell secretes. Both factors stimulated GH secretion in
      a dose-dependent fashion, with PACAP being more effective. PACAP increased both
      the number of cells secreting and the mean amount of hormone secreted per cell.
      In contrast, GHRP increased the number of secreting cells, although it had no
      effect on the amount of secretion per cell. GH secretion induced by GHRH, GHRP,
      and PACAP was inhibited by SRIF, but the effect was predominantly on the number
      of cells secreting rather than the amount secreted per cell. Specific antagonists
      to GHRP and GHRH inhibited GH secretion induced by the respective agonist but not
      that induced by the other factor nor by PACAP. These findings confirm the complex
      nature of the regulation of GH secretion at the level of the somatotrope. At
      least three factors, operating via distinct receptors, are able to increase GH
      secretion. In addition, they ascribe a potential physiological role for the
      hitherto putative hypophysiotropic factor PACAP.

PMID- 1346382
TI  - The effect of chronic phenytoin treatment on serum lipid profile in adult
      epileptic patients.
AB  - Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL),
      and very-low-density lipoprotein cholesterol, apolipoproteins A, A1, and B and
      gamma-glutamyltransferase (ggt) serum concentrations were measured in 100 adult
      epileptic patients receiving chronic phenytoin (PHT) treatment and in 100 control
      subjects. In relation to controls, patients showed higher HDL cholesterol,
      apolipoproteins A and A1, and ggt levels and lower LDL cholesterol and
      apolipoprotein B values; the significance of the results was greater in women
      than in men. Among patients, ggt levels were positively correlated with PHT
      plasma concentrations; likewise, a negative correlation was found between the
      apolipoprotein A/A1 ratio and the PHT and ggt plasma levels, and a positive
      correlation between the apolipoprotein A/A1 ratio and the LDL/HDL cholesterol
      ratio. These data indicate that PHT exerts a beneficial effect on the serum
      lipids profile.

PMID- 1346383
TI  - Synthesis and binding of peptide T and aminoacyl derivatives to CD4+ lymphocytes.
AB  - 1. Peptide T and four other aminoacyl derivatives of this octapeptide were
      synthesized on solid phase support using the Boc and Fmoc procedures. 2. The
      octapeptides were modified by chloroacetylation and radiolabelled by halogen
      exchange with 125I. 3. Purified and crude extracts of lymphocytes were used to
      determine the binding of the octapeptides at different concentrations.

PMID- 1346384
TI  - Reinnervation of syngeneic mouse pancreatic islets transplanted into renal
      subcapsular space.
AB  - A syngeneic transplantation of 150 islets into the subcapsular renal space was
      performed on normoglycemic or alloxan-induced diabetic male C57BL/6 mice. Six, 8,
      14, or 20-21 wk after transplantation, the graft-bearing kidney was removed and
      processed for microscopical examinations with indirect immunofluorescence for
      neuropeptides and tyrosine hydroxylase, and with acetylcholinesterase staining to
      visualize nerve fibers within the graft. Six weeks after implantation, only a few
      scattered nerve fibers were observed within the grafts. A progressive increase in
      the number of nerves was observed until 14 wk after transplantation, after which,
      a stable level was reached. Alloxan-induced diabetic mice showed quantitatively
      and qualitatively similar reinnervation to normoglycemic mice 20 wk after
      transplantation. The findings demonstrate the presence of sympathetic nerve
      fibers (containing tyrosine hydroxylase and neuropeptide Y), mainly accompanying
      ingrowing blood vessels; parasympathetic nerve fibers (containing
      acetylcholinesterase and vasoactive intestinal peptide), possibly reaching the
      graft from the adjacent renal capsule; and afferent nerve fibers (containing
      substance P and calcitonin gene-related peptide), which were less numerous. The
      data suggest that transplanted islets become reinnervated by ingrowth of nerve
      fibers from the implantation organ and that several types of nerves are present.

PMID- 1346385
TI  - Preferential mutation of the neurofibromatosis type 1 gene in paternally derived
      chromosomes.
AB  - An interesting feature of neurofibromatosis type 1 (NF1) is its high mutation
      rate of 1 x 10(-4) per gamete per generation. The molecular basis for frequent
      NF1 mutation in unknown; the gene is not deletion prone. We have found that in
      all ten families examined, the apparent new NF1 mutation occurred on the
      paternally-derived chromosome. The probability of observing this result by chance
      is less than 0.001 assuming an equal frequency of mutation of paternal and
      maternal NF1 genes. We hypothesize a role for genomic imprinting that may either
      enhance mutation of the paternal NF1 gene or confer protection from mutation to
      the maternal NF1 gene.

PMID- 1346386
TI  - Sib pair linkage analysis of renin gene haplotypes in human essential
      hypertension.
AB  - Although essential arterial hypertension is believed to have a strong genetic
      predisposition, the gene(s) responsible are unknown. The mechanisms underlying
      the regulation of blood pressure and experimental studies place the renin gene
      among the main candidate genes that need to be tested in humans. We tested the
      hypothesis of a linkage between the renin gene and essential hypertension using
      the affected sib pair method. Siblings (133 subjects, 52.1 +/- 10.9 years) from
      57 families were selected for sustained hypertension (160.7 +/- 22.9/99.5 +/-
      12.8 mmHg with 80% of patients under antihypertensive treatment), of early onset
      (40.7 +/- 12.0 years), in the absence of obesity, diabetes mellitus, and
      secondary hypertension. Eight renin haplotypes were generated from three
      diallelic renin restriction fragment length polymorphisms (RFLPs) (TaqI, HinfI,
      HindIII) located throughout the renin gene. The allelic concordance between the
      sib pairs was analyzed by identity by state relationships for 98 sib pairs (41
      for 41 couples, 39 for 13 trios, 18 for 3 quartets). Allelic frequencies in the
      57 hypertensive probands were similar to those observed among 102 hypertensive
      subjects studied previously. Six of eight possible haplotypes were observed, the
      informativity of the marker corresponded to 70% of heterozygosity. Allelic
      concordance for all sib pairs according to sibship size was not significantly
      different from that expected under the hypothesis of no linkage (t = 0.52, P =
      0.15) reflecting only a small excess of renin alleles shared by the hypertensive
      sibs (1.44 +/- 0.6 vs 1.36 +/- 0.6). Likewise the linkage hypothesis was
      unsupported by weighted estimates to correct for possible bias due to large
      sibship size. Thus, the sib pair analysis suggests that the renin gene does not
      have a frequent role in the pathogenesis of essential hypertension; further more
      powerful linkage studies or other approaches will be needed to detect
      contributions at the renin locus to the heritability of essential hypertension.

PMID- 1346387
TI  - Estimating the stability of the proposed imprinted state of the fragile-X
      mutation when transmitted by females.
AB  - Fragile-X syndrome is a major cause of mental retardation in humans. The X
      inactivation imprinting model accounts for the unusual pattern of inheritance and
      expression of this syndrome. According to this model, the fragile-X mutation
      creates a local block to the attempted reactivation of the mutant X chromosome
      prior to oogenesis. This local block results in an "imprinted" fragile-X
      chromosome that is deleterious in males and in females for whom this chromosome
      is predominantly the active X chromosome. The imprinted state of the fragile-X
      mutation is inferred to be stable when transmitted by an imprinted female because
      the penetrance of the syndrome in sons of affected females is estimated to be
      1.0. To provide a more precise estimate of the stability of the proposed fragile
      X imprint, we have analyzed published pedigrees that include restriction fragment
      length polymorphism and cytogenetic data from sibships with mothers who are
      interpreted as having an imprinted fragile-X allele. We conclude that the fragile
      X imprint was stable in 46 out of 48 female meioses. This analysis leads to a
      preliminary estimate of about 96% for the stability of the imprint through female
      meiosis. Two imprinted females had progeny who appeared to be carriers of a
      nonimprinted fragile-X allele. If this interpretation is correct, then reversion
      from the imprinted to the nonimprinted state, or "erasure," can occasionally
      occur when the mutant fragile-X allele is transmitted by an imprinted female. We
      discuss the genetic and epigenetic significance of possible female erasure. We
      request DNA and cytogenetic information from unpublished pedigrees to quantify
      further the stability, during female meiosis, of the proposed imprinted state of
      the mutant fragile-X allele.

PMID- 1346388
TI  - A rare genetic variant of the T cell receptor gamma joining segment TRGJI.

PMID- 1346389
TI  - Assignment of the angiogenin gene to mouse chromosome 14 using a rapid PCR-RFLP
      mapping technique.

PMID- 1346390
TI  - Localization of a gene for the human low-voltage EEG on 20q and genetic
      heterogeneity.
AB  - The localization of a gene responsible for a normal variant of the human
      electroencephalogram to the distal part of chromosome 20q is reported. A linkage
      analysis, including 17 families with 191 individuals, tested with 73 RFLPs and 22
      blood and serological markers, was performed for the low-voltage
      electroencephalogram. This is a normal variant of the human electroencephalogram
      with an autosomal dominant mode of inheritance. The results present strong
      evidence for close linkage with the highly polymorphic marker CMM6 (D20S19) and
      for genetic heterogeneity.

PMID- 1346391
TI  - The human heat-shock genes HSPA6 and HSPA7 are both expressed and localize to
      chromosome 1.
AB  - HSPA6 is a member of the human heat-shock protein gene family, encoding a basic
      70-kDa protein, with unique induction characteristics (Leung et al., 1990,
      Biochem. J. 267: 125-132). Hybridization analyses with a somatic cell hybrid DNA
      panel localized the gene to chromosome 1q. The highly related HSPA7 DNA sequence
      (Voellmy et al., 1985, Proc. Natl. Acad. Sci. USA 82: 4949-4953) colocalized.
      Both HSPA6 and HSPA7 represent functional genes, as determined by analyses of
      mRNA from heat-shocked human cells using specific oligonucleotides, although
      their pattern of expression differed. Neither mRNA was detected in the absence of
      heat stress. A BamHI polymorphism in the HSPA7 gene was present in a
      predominantly Asian population.

PMID- 1346392
TI  - Alpha 2-C10 adrenergic receptors expressed in rat 1 fibroblasts can regulate both
      adenylylcyclase and phospholipase D-mediated hydrolysis of phosphatidylcholine by
      interacting with pertussis toxin-sensitive guanine nucleotide-binding proteins.
AB  - The alpha 2-C10 adrenergic receptor from human platelets was expressed
      permanently in Rat-1 fibroblasts. A series of clones that varied in expression of
      the receptor from 0 to 3.5 pmol/mg of membrane protein were isolated. We have
      demonstrated recently in cells of one of these clones (1C) that the alpha 2-C10
      receptor interacts directly with two distinct pertussis toxin-sensitive G
      proteins, Gi2 and Gi3 (Milligan, G., Carr, C., Gould, G. W., Mullaney, I., and
      Lavan, B.E. (1991) J. Biol. Chem. 266, 6447-6455). High affinity GTPase activity
      in membranes of cells from the various clones was stimulated by the addition of
      the alpha 2-adrenergic agonist UK14304, defining that the receptor coupled
      productively to the G-protein signaling system. Maximal stimulation of high
      affinity GTPase activity correlated with the levels of receptor expressed. Clones
      expressing the receptor also demonstrated agonist-mediated inhibition of
      adenylylcyclase. Futhermore, the alpha 2-C10 receptor in one clone (1C), but not
      other clones, promoted a marked stimulation in the generation of water-soluble
      products derived from phosphatidylcholine. The concentration of UK14304 required
      to produce half-maximal regulation of GTPase activity (20-30 nM), of forskolin
      amplified adenylylcyclase activity (30-40 nM), and of choline generation (30-40
      nM) were similar. Transphosphatidylation experiments with cells of clone 1C
      indicated that the receptor-mediated hydrolysis of phosphatidylcholine was via
      the action of a phospholipase D. All of these effects were attenuated by
      pretreatment of the cells with pertussis toxin. Dose-effect curves of pertussis
      toxin-treatment demonstrated similar effective concentrations of the toxin in
      causing endogenous ADP-ribosylation of both Gi2 and Gi3, inhibition of receptor
      stimulated GTPase activity, and phospholipase D activity. Receptor activation of
      phospholipase D activity was not dependent upon prior phospholipase C-dependent
      activation of protein kinase C, as alpha 2-adrenergic stimulation of inositol
      phosphate production was negligible and the presence of the selective protein
      kinase C inhibitor RO-31-8220, at concentrations up to 10 microM, had no effect
      on UK14304-mediated production of phosphatidylbutanol. These results demonstrate
      that expression of the alpha 2-C10 receptor in a heterologous system can result
      in receptor regulation of signaling elements that appear not to be primary
      targets for the receptor in vivo. Such results are important in respect to recent
      observations that transfection of a single defined receptor into separate cell
      lines can lead to the regulation of distinct effector systems (Vallar, L., Muca,
      C., Magni, M., Albert, P., Bunzow, J., Meldolesi, J. and Civelli, O. (1990) J.
      Biol. Chem. 265, 10320-10326).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1346393
TI  - Bacterial expression, purification, and functional mapping of the amyloid beta/A4
      protein precursor.
AB  - The secreted form of Alzheimer amyloid beta/A4 protein precursor (APP) has been
      shown to be involved in cell growth regulation (Saitoh, T., Sundsmo, M., Roch, J.
      M., Kimura, N., Cole, G., Schubert, D., Oltersdorf, T., and Schenk, D.B. (1989)
      Cell 58, 615-622). Using a strong prokaryotic expression system, we expressed, in
      Escherichia coli, peptide fragments covering different regions of the secreted
      form of APP-695. The longest of these fragments (KB75, 572 amino acids from Val
      20 to Ile-591), which contained neither the Kunitz-type protease inhibitor (KPI)
      domain nor the amyloid beta/A4-protein domain, was purified and shown to be
      biologically active in terms of growth regulation. Two other APP fragments (KB48,
      316 amino acids from Val-20 to Met-335; and RB17, 150 amino acids from Thr-296 to
      Pro-445), overlapping by only 40 amino acids at a close site C-terminal to the
      KPI insertion site, were also active. Furthermore, a chemically synthesized 40
      residue peptide corresponding to this region of overlap also stimulated the
      growth of A-1 fibroblasts. These results establish the presence of growth
      promoting activity in the secreted form of APP-695 and suggest that the site of
      this activity of APP-695 lies within a 40-amino acid domain next to the KPI
      insertion site.

PMID- 1346394
TI  - Genomic structure of keratinocyte transglutaminase. Recruitment of new exon for
      modified function.
AB  - The gene for keratinocyte transglutaminase (TGK) spans 14 kilobase pairs and
      contains 15 exons. Many features of the TGK gene are very similar, if not
      identical, to those of the gene encoding the catalytic subunit of human clotting
      factor XIII: they have the same number of exons, corresponding introns always
      interrupt the coding region in the same phase of the codon, and most exons are of
      similar size (10 or 15 are exactly the same size). In these respects, the TGK and
      factor XIII catalytic subunit genes resemble each other more than either
      resembles the gene for erythrocyte band 4.2, a noncatalytic transglutaminase
      superfamily member. Exon II in both the TGK and factor XIII genes encodes an
      amino-terminal extension of nonhomologous sequence which in each protein confers
      a specialized function (membrane anchorage or activation of cross-linking,
      respectively). This suggests that the evolution of these genes included
      recruitment of a new exon to modify the enzyme action. Southern blots of genomic
      DNA reveal the presence of a TGK-like gene in birds, amphibians, and fish, but
      not in flies.

PMID- 1346395
TI  - Glucose regulation of acetyl-CoA carboxylase in hepatoma and islet cells.
AB  - The regulation of acetyl-CoA carboxylase (ACC) by glucose and other fuel
      molecules has been examined in Fao Reuber hepatoma cells and Syrian hamster
      insulin tumor (HIT) cells in order to determine whether lipogenic substrates
      acutely alter ACC activity and to examine the mechanism of such regulation. In
      Fao cells, preincubated in simple medium without substrates, glucose addition
      results in a rapid activation of ACC. This effect, mimicked by other fuels such
      as lactate, is characterized by an increase in enzyme Vmax and a decrease in the
      activation constant for citrate. Several lines of evidence indicate that this
      activation of ACC is due to enzyme dephosphorylation, including the kinetic
      changes observed, the persistence of enzyme activation through ACC isolation, the
      necessity of inclusion of sodium fluoride/EDTA in the cell lysis buffer for
      preservation of the glucose-induced change, and the direct demonstration of
      diminished 32P-labeling of ACC after glucose exposure. Identical effects of
      glucose are also observed in HIT cells, although the ACC activation is smaller in
      magnitude and less sensitive than that observed in Fao cells. Other insulin
      secretagogues such as glutamine, lactate, and isobutylmethylxanthine are also
      found to activate HIT ACC. Others have suggested that glucose-induced changes in
      malonyl-CoA in beta-cells may be linked to glucose-induced insulin secretion.
      However, studies conducted in late passage HIT cells, which fail to secrete
      insulin in response to glucose stimulation, reveal the same glucose-induced
      activation seen in early passages, secretion-competent HIT cells, suggesting that
      glucose-induced ACC activation is not by itself sufficient to provoke insulin
      secretion. Taken together, these findings indicate that glucose and other fuel
      molecules can play a major role in the rapid regulation of the fatty acid
      synthesis pathway. The activation of fatty acid synthesis by substrate-induced
      ACC dephosphorylation insures ultimate fuel storage of glucose-derived carbon as
      fatty acid, while substrate-induced increases in the ACC product, malonyl CoA,
      would serve to simultaneously limit the rate of fatty acid oxidation through its
      allosteric regulation of carnitine palmitoyltransferase I.

PMID- 1346396
TI  - Evidence for an apical sorting signal on the ectodomain of human aminopeptidase
      N.
AB  - In polarized epithelial cells aminopeptidase N is targeted to the apical
      membrane. The aim of this study was to determine whether a sorting signal is
      necessary for its correct transport to the apical membrane and, if so, to
      localize this sorting signal to one of the domains of the transmembrane protein.
      Anchor-minus aminopeptidase N, consisting of the hemagglutinin signal peptide
      including its cleavage site, and the ectoplasmic domain of human aminopeptidase N
      were stably expressed in Madin-Darby canine kidney cells cultured on
      polycarbonate filters. By measurement of the enzymatic activity it was found that
      the anchor-minus aminopeptidase N was secreted in a polarized manner to the
      apical side. As a reference the secretion of the secretory granule protein,
      cystatin C, was likewise studied. Cystatin C was found to be secreted in a
      nonpolarized manner to both domains. Our data thus show that human aminopeptidase
      N carries an apical sorting signal and that it is localized on the ectodomain of
      the enzyme.

PMID- 1346397
TI  - Calcium ionophore treatment impairs the sterol-mediated suppression of 3-hydroxy
      3-methylglutaryl-coenzyme A reductase, 3-hydroxy-3-methylglutaryl-coenzyme A
      synthase, and farnesyl diphosphate synthetase.
AB  - We report that the sterol-mediated suppression of the mRNA levels of three
      cholesterogenic enzymes, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase, HMG-CoA synthase, and farnesyl diphosphate (FPP) synthetase is
      partially overcome by the calcium ionophore A23187. Addition of A23187 to the
      human monocytic leukemia cell line THP-1 in the presence of fetal calf serum led
      to rapid increases in mRNA concentration of up to 40-fold for HMG-CoA synthase
      and 15-fold for HMG-CoA reductase with little or no change in FPP synthetase mRNA
      levels. Treatment of HepG2 cells with A23187 resulted in approximately 2-4-fold
      increases in the mRNA levels for these three enzymes. The increases in HMG-CoA
      synthase and HMG-CoA reductase mRNAs were maximal after treatment of THP-1 cells
      with 10 micrograms/ml A23187 for 3 h. The stimulation was blocked by actinomycin
      D but not by cycloheximide treatment. Ionophore treatment had no effect on the
      half-lives of the mRNAs for HMG-CoA reductase and HMG-CoA synthase. Surprisingly,
      the addition of A23187 to THP-1 cells incubated in the presence of 25
      hydroxycholesterol and mevalonic acid also led to significant increases in the
      mRNA levels for HMG-CoA reductase and HMG-CoA synthase. Finally, the stimulation
      of these mRNA levels by A23187 was reduced in cells in which protein kinase C had
      been inactivated by preincubation of the cells with a phorbol ester. Taken
      together, these data suggest that A23187 treatment results in increased
      transcription of HMG-CoA reductase, HMG-CoA synthase, and, in some cell types,
      FPP synthetase by a mechanism that does not involve de novo protein synthesis. We
      speculate that A23187 treatment results in the modification of a trans-acting
      factor(s) which is common for the transcription of all these genes.

PMID- 1346398
TI  - Generation of signals activating neutrophil functions by leukocyte integrins: LFA
      1 and gp150/95, but not CR3, are able to stimulate the respiratory burst of human
      neutrophils.
AB  - To address the question whether leukocyte integrins are able to generate signals
      activating neutrophil functions, we investigated the capability of mAbs against
      the common beta chain (CD18), or the distinct alpha chains of CR3, LFA-1, or
      gp150/95, to activate neutrophil respiratory burst. These investigations were
      performed with mAbs bound to protein A immobilized to tissue culture polystyrene.
      Neutrophils plated in wells coated with the anti-CD18 mAbs IB4 and 60.3 released
      H2O2; H2O2 release did not occur when neutrophils were plated in wells coated
      with an irrelevant, isotype-matched mAb (OKDR), or with mAbs against other
      molecules (CD16, beta 2-microglobulin) expressed on the neutrophil surface at the
      same density of CD18. Four different mAbs, OKM1, OKM9, OKM10, 60.1, which
      recognize distinct epitopes of CR3 were unable to trigger H2O2 or O2- release
      from neutrophils. However, mAbs against LFA-1 or gp150/95 triggered both H2O2 and
      O2- release from neutrophils. Stimulation of neutrophils respiratory burst by
      both anti-CD18, and anti-LFA-1 or gp150/95 mAbs was totally inhibited by the
      microfilaments disrupting agent, cytochalasin B, and by a permeable cAMP
      analogue. While the capability to activate neutrophil respiratory burst was
      restricted to anti-LFA-1 and gp150/95 mAbs, we observed that mAbs against all
      members of leukocyte integrins, including CR3, were able to trigger neutrophil
      spreading. These findings indicate that, in neutrophils, all three leukocyte
      integrins can generate signals activating spreading, but only LFA-1 and gp150/95
      can generate signals involved in activation of the respiratory burst. This
      observation can be relevant to understand the mechanisms responsible for the
      activation of neutrophil respiratory burst by tumor necrosis factor-alpha, which
      has been shown to be strictly dependent on expression of leukocyte integrins
      (Nathan, C., S. Srimal, C. Farber, E. Sanchez, L. Kabbash, A. Asch, J. Gailit,
      and S. Wright. 1989. J. Cell Biol. 109:13411349.

PMID- 1346399
TI  - Epidermal growth factor and transforming growth factor-alpha decrease gamma
      interferon receptors and induction of intercellular adhesion molecule (ICAM-1) on
      cultured keratinocytes.
AB  - The link between the epidermal keratinocytes of the skin and the activated T
      lymphocytes of the immune system is mediated by a variety of cytokines, including
      gamma interferon (IFN-gamma). We studied the influence of keratinocyte mitogens
      such as transforming growth factor-alpha (TGF-alpha), epidermal growth factor
      (EGF), and somatomedin-C (SM-C) on the ligand binding of 32P-labeled IFN-gamma to
      cultured keratinocytes derived from normal appearing adult human skin.
      Keratinocytes placed in a medium devoid of mitogens become growth arrested, and
      these quiescent cells expressed 2.4 times (28,900 versus 12,200 sites/cell) as
      many high affinity IFN-gamma receptors (Kd = 0.22 nM) compared to keratinocytes
      which were actively growing in medium containing TGF-alpha (25 ng/ml) or EGF (10
      ng/ml). The reduction in IFN-gamma receptor sites by TGF-alpha/EGF was mitogen
      specific, as adding SM-C (500 ng/ml) did not have any effect on ligand binding,
      although it similarly stimulated keratinocyte growth. The reduction in IFN-gamma
      receptors was time dependent, occurring primarily after 24-48 hours of change in
      tissue culture conditions. The reduction in the number of high affinity IFN-gamma
      receptors by TGF-alpha/EGF had immunobiological consequences, because quiescent
      keratinocytes in basal medium had an increased expression of HLA-DR and
      intercellular adhesion molecule-1 (ICAM-1) induced by IFN-gamma, compared to
      actively growing TGF-alpha/EGF treated keratinocytes. These results suggest that
      rapidly proliferating keratinocytes exposed to TGF-alpha/EGF but not SM-C are
      capable of altering their response to IFN-gamma by decreasing their number of
      cell surface high affinity receptors for IFN-gamma.

PMID- 1346400
TI  - TGF-beta-induced G2/M delay in proliferating rabbit articular chondrocytes is
      associated with an enhancement of replication rate and a cAMP decrease: possible
      involvement of pertussis toxin-sensitive pathway.
AB  - This study was undertaken to gain more insight into the mechanism whereby TGF
      beta influences the cell cycle progression of cultured rabbit articular
      chondrocytes. Using proliferating chondrocytes in fetal calf serum-containing
      medium, we have previously shown that TGF-beta induced a recruitment of cells at
      the end of the S phase (G2/M) observed 24 h after addition. The delayed cells may
      then be released, producing a proliferative effect at 48 h, provided a
      substantial amount of FCS (10%) is present in the medium. Otherwise, in low level
      of serum (2% FCS, for example), only inhibition of cell proliferation is
      observed. In chondrocytes synchronized in S phase by a thymidine block, we
      investigated here the time-course incorporation of [3H]-thymidine into DNA, the
      cell cycle traverse by flow cytofluorometric study of DNA content, the expression
      of PCNA (Proliferating Cell Nuclear Antigen), and cAMP levels. The data
      demonstrate that TGF-beta provoked a decrease of cAMP content (0.5-1 h) followed
      by an enhancement of the DNA synthesis rate (4 h) which was detectable through
      cytofluorometric analysis and [3H]-thymidine labeling and correlated with the
      PCNA expression. In contrast, addition of cAMP analogues to the cultures resulted
      in an inhibition of replication rate. We also showed that pertussis toxin
      produced a decrease of the DNA synthesis rate, in a transient manner and only in
      the presence of TGF-beta. All these results suggest that TGF-beta may accelerate
      the replication process of cyclized chondrocytes, making then accumulate at the
      G2/M boundary, via a mechanism that could involve the adenylate cyclase activity
      and a Gi-protein. The factor might be responsible for producing a pool of cells
      having already replicated their DNA and therefore capable of re-entering the cell
      cycle without delay. This cell population could serve as a tissue reserve able to
      induce a mitosis wave when necessary--for example, in the repair of tissue
      damage.

PMID- 1346401
TI  - Differential expression of asialoglycoprotein receptor subunits in the endocytic
      compartment during liver regeneration.
AB  - Asialoglycoprotein receptors, responsible for the removal of circulating
      asialoglycoproteins by the liver, are located in at least two different membrane
      locations in hepatocytes. Receptors on the cell surface account only for a minor
      proportion (20-36%), for the majority of receptors in the liver are located
      intracellularly, mainly in the endocytic membrane networks. An understanding of
      the basis of receptor distribution and the underlying trafficking of receptors
      between the hepatocyte's polarised cell surface and the endocytic compartment
      would be aided if biochemical differences between the receptors in these pools
      were established. We now show, using three antibodies that recognise the receptor
      subunits in rat liver (RHL-1, RHL-2 and RHL-3), that the asialoglycoprotein
      receptors located in the plasma membrane domains and the endocytic compartment
      differ in oligomeric composition, sialic acid content, and solubility in Triton X
      114 using two-phase systems. It is well established that the expression of the
      asialoglycoprotein receptor is down-regulated in livers regenerating after a
      partial hepatectomy. We demonstrate that the levels of the receptor subtype that
      is located mainly in the endocytic compartment (RHL-1, 42 kDa) was elevated in
      regenerating liver by agents that regulate cAMP production, whereas the levels of
      the other receptor subtypes remained unchanged. The asialoglycoprotein receptor
      subtypes that are present in different subcellular locations are thus regulated
      independently.

PMID- 1346402
TI  - Induction of proliferating cell nuclear antigen (PCNA) complex formation in
      quiescent fibroblasts from a xeroderma pigmentosum patient.
AB  - Accumulated evidence indicates that proliferating cell nuclear antigen (PCNA) is
      an auxiliary protein of DNA polymerase delta and forms tight association with DNA
      replication sites during DNA replication or DNA repair synthesis. In this study,
      such PCNA complex formation was investigated by the indirect immunofluorescence
      method, using both normal human fibroblasts and those derived from a xeroderma
      pigmentosum group A (XP-A) patient. XP-A fibroblasts in both proliferating and
      quiescent states did not show any differences from normal fibroblasts in the
      properties of PCNA-staining in the untreated conditions. The PCNA complex
      formation was induced in quiescent normal fibroblasts by both ultraviolet light
      (UV)- and X-irradiation, whereas in XP-A fibroblasts it was induced by X
      irradiation, but not by UV-irradiation. However, PCNA complex was induced in
      quiescent XP-A fibroblasts by UV-irradiation when the cells had previously
      incorporated 5-bromodeoxyuridine (BrdU). These observations indicate a close
      correlation of PCNA complex formation and unscheduled DNA synthesis (UDS). Thus,
      it was concluded that PCNA complex formation was commonly induced in at least
      three conditions to produce UDS in spite of different types of DNA damages and
      DNA repair mechanisms.

PMID- 1346403
TI  - Immunological changes in cats with concurrent Toxoplasma gondii and feline
      immunodeficiency virus infections.
AB  - To examine the immunological changes in cats concurrently infected with feline
      immunodeficiency virus (FIV) and Toxoplasma gondii, kittens (four per group) were
      inoculated with FIV, T. gondii, both agents, or no pathogens. Blood mononuclear
      cells and plasma were collected weekly for lymphocyte assays and serology. At
      week 14, spleen and lymph node cells were used for lymphocyte assays; brains and
      mesenteric lymph nodes were used for isolation of T. gondii. More T. gondii
      organisms were present in tissues of the dually infected cats than in tissues of
      cats with toxoplasmosis alone. Two dually infected cats and one cat infected with
      T. gondii developed chorioretinitis. Spleen, lymph node, and blood mononuclear
      cells from dually infected cats had the greatest reduction in mitogenic
      responses. By week 3, cats infected with FIV underwent a decrease in the number
      of CD4 cells that was not changed by concurrent T. gondii infection; the number
      of CD8 cells increased only in cats infected with T. gondii alone. For cats
      infected with T. gondii, the responses of lymphocytes to T. gondii antigen were
      not affected by FIV infection; the responses to FIV antigen were negligible in
      all groups. Overall, this study indicates that FIV infection favors T. gondii
      proliferation. Also, the establishment of toxoplasmosis may enhance FIV-induced
      immunodeficiency and is likely to cause a more rapid disease progression than
      that from infection with FIV alone.

PMID- 1346404
TI  - Overview from the International Conference on Long-Term Tamoxifen Therapy for
      Breast Cancer.
AB  - The development of tamoxifen therapy to treat selected patients, with all stages
      of breast cancer, has provided the clinical community with an efficacious and
      safe drug for long-term therapy. Issues of safety are under constant review, but
      justified concerns about high doses of tamoxifen acting as a promoter of liver
      cancer in rats or as a promoter of endometrial cancer in women have not, as yet,
      proved to be of clinical relevance. The situation will continue to be reviewed
      during the development of the prevention studies in Europe and the United States
      because an improvement in women's health is the ultimate goal of these programs.
      The hallmark for the successful development of tamoxifen has been the close
      cooperation between the laboratory and the clinic. The clinical strategy of long
      term tamoxifen therapy is a direct application of a laboratory concept.
      Furthermore, potential problems in the clinic have been identified in the
      laboratory, and the clinical community has responded quickly to evaluate the real
      risks to the patient population. This close cooperation will continue. Issues of
      drug resistance, new antiestrogen development, and the application of the
      knowledge about steroid receptors to develop targeted gene therapies are being
      addressed so that additional treatment approaches for breast cancer will be in
      place by the turn of the century.

PMID- 1346405
TI  - Overexpression of the MDR1 gene and P-glycoprotein in human hepatocellular
      carcinoma.

PMID- 1346406
TI  - The new AIDS case definition. Implications for San Francisco.

PMID- 1346407
TI  - [Memory at the synaptic level].
AB  - Ever since the discovery of the synapse at the end of the last century it has
      been surmised that elementary neural changes underlying learning and memory are
      located at the junctions between nerve cells. Experimental studies during the
      past 20 years have demonstrated the existence of several synaptic modification
      processes, the most prominent being long-term potentiation (LTP) in the
      hippocampus. Several links between LTP and learning/memory have been established.
      For example, memory impairment in older rats is well correlated, with increasing
      decline of LTP, and N-methyl-D-aspartate (NMDA) receptor antagonists give rise to
      a parallel blockade of LTP and of spatial task learning. Studies on rats in a
      natural learning situation have also demonstrated 'spontaneous' occurrence of
      LTP. LTP is induced as a consequence of coincident pre- and post-synaptic
      activity, and thus in conformity with a basic principle of learning theory known
      as Hebb's rule. Responsible for this associative induction is the NMDA-subtype of
      glutamate receptor channel with its unique property of being both transmitter and
      voltage controlled. Its opening allows calcium ions to enter the postsynaptic
      cell and to initiate biochemical processes leading to a lasting synaptic
      modification. The nature of the critical processes involved in establishing the
      modification(s) is uncertain, although the participation of calcium-activated
      protein kinases seems likely. There is still considerable controversy whether the
      actual change occurs postsynaptically, or presynaptically, triggered via a
      retrograde signal from the postsynaptic cell. LTP similar to that in the
      hippocampus has recently been described for various neocortical regions.

PMID- 1346408
TI  - Comparison of artemether and chloroquine for severe malaria in Gambian children.
AB  - Artemether is an oil-soluble methyl ether of artemesinin (qinghaosu). It has been
      studied extensively in China, where it has been shown to be rapidly effective in
      severe falciparum malaria. Nearly all the patients studied previously were
      adults. We have investigated the efficacy of artemether in children with moderate
      or severe falciparum malaria. In the preliminary study of moderately severe
      malaria, 30 Gambian children were randomised in pairs to receive either
      intramuscular artemether (4 mg/kg loading dose followed by 2 mg/kg daily) or
      intramuscular chloroquine ('Nivaquine') 3.5 mg base/kg every 6 h. Both drugs were
      well tolerated and rapidly effective. The times to parasite clearance were
      significantly shorter in the artemether recipients (mean 36.7 [SD 11.3] vs 48.4
      [16.8] h, p less than 0.05). 43 children with severe malaria were then randomised
      to receive intramuscular treatment with the same regimens of artemether (n = 21)
      or chloroquine (n = 22) as used in the preliminary study. 8 children (19%) died.
      There were no significant differences between the two groups in the clinical,
      haematological, biochemical, or parasitological measures of therapeutic response
      in survivors and there was no evidence of local or systemic toxicity. Despite
      similar parasite counts on admission, clearance times overall were longer in
      severe malaria than in moderate malaria. Artemether is a well tolerated and
      rapidly effective parenteral treatment for severe malaria in children, and would
      be especially valuable in areas with chloroquine-resistant P falciparum.

PMID- 1346409
TI  - Lymphocytic sialadenitis of Sjogren's syndrome associated with chronic hepatitis
      C virus liver disease.
AB  - Viral infection has often been suggested as a possible cause of Sjogren's
      syndrome or chronic lymphocytic sialadenitis, and Epstein-Barr virus has been
      found in the salivary glands of patients with this condition. After we had noted
      Sjogren's syndrome in several patients infected with hepatitis C virus (HCV), a
      virus also excreted in saliva, we set up a prospective study to investigate the
      association of chronic lymphocytic sialadenitis, with or without symptoms, to
      chronic HCV liver disease. The histological appearances of labial salivary glands
      in patients with proven HCV hepatitis or cirrhosis were compared with those in
      dead controls. Histological changes characteristic of Sjogren's syndrome were
      significantly more common in HCV-infected patients (16 of 28, 57%) compared with
      controls (1 of 20, 5%). Focal lymphocytic sialadenitis characteristic of
      Sjogren's syndrome (though only 10 patients had xerostomia and none complained of
      xerophthalmia) appears to be common in patients with chronic HCV liver disease;
      if this association is confirmed, identification of the underlying mechanism may
      improve our understanding of both disorders.

PMID- 1346410
TI  - Trial of cyclosporin in corticosteroid-dependent chronic severe asthma.
AB  - The treatment of chronic severe asthma is unsatisfactory for many patients. In a
      randomised, double-blind, placebo-controlled, crossover trial we have tested
      whether cyclosporin, which is thought to act primarily by inhibition of T
      lymphocyte activation, improves lung function in corticosteroid-dependent
      asthmatics. After a 4-week run-in period, 33 patients with longstanding asthma
      (mean duration 27 years), and who had required continuous oral corticosteroids
      for a mean of 9.3 years, were randomised to receive either cyclosporin (initial
      dose 5 mg/kg per day) or placebo for 12 weeks, crossing over after a 2-week
      washout period. Mean baseline forced expiratory volume in 1 s (FEV1) was 60.1% of
      the predicted value. 2 patients failed to complete the protocol and 1 withdrew
      because of hypertrichosis. Cyclosporin therapy resulted in a mean increase above
      placebo of 12.0% in morning peak expiratory flow rate (PEFR; p less than 0.004)
      and 17.6% in FEV1 (p less than 0.001). The frequency of disease exacerbations
      requiring an increased prednisolone dose was reduced by 48% in patients on
      cyclosporin compared with placebo (p less than 0.02). Diurnal variation in PEFR
      decreased by a mean of 27.6% (p = 0.04). Cyclosporin for 12 weeks was well
      tolerated by this group of chronic asthmatics, in whom the mean whole-blood
      trough concentration was 152 micrograms/l. These findings provide further
      evidence of a role for activated T lymphocytes in the pathogenesis of asthma.
      Specific pharmacological targeting of this cell could form the basis of a novel
      approach to the treatment of asthma.

PMID- 1346411
TI  - Enzyme-linked immunosorbent assay for diagnosis of acute sporadic hepatitis E in
      Egyptian children.
AB  - Hepatitis E virus (HEV) is thought to be a cause of enterically transmitted non
      A, non-B (ET-NANB) hepatitis. Waterborne epidemics have been recorded in many
      developing countries, mainly affecting young-to-middle-aged adults; sporadic
      infection and overt illness in children are rare. However, a convenient and
      sensitive diagnostic test for HEV infection is not yet available. We now report
      the use of a solid-phase enzyme-linked immunoassay (ELISA) that detects IgM and
      IgG antibody to HEV. In a prospective study of endemic acute hepatitis during
      1986 in rural Benha, Egypt, 15 (42%) of 36 children with NANB hepatitis (from
      whom convalescent-phase sera were available every 3 months to 9 or 12 months)
      were positive for anti-HEV-IgG by ELISA. Of 20 sera from healthy Benha children
      (controls), 5 (25%) were also positive for anti-HEV-IgG. When evaluated for anti
      HEV-IgM, 6 of the 15 IgG-positive children, but none of the controls, were IgM
      positive and were thus regarded as having confirmed acute HEV infections. These 6
      cases together with 2 presumptive cases (IgM negative, IgG seroconversion from
      positive to negative) presented sporadically over 9 months. This ELISA is a
      convenient method for the diagnosis of HEV infection; we have shown that the
      disease is present in Egypt, that it can occur endemically as sporadic cases, and
      that children do have overt infection.

PMID- 1346412
TI  - Balloon dilatation of the arterial duct in congenital heart disease.
AB  - The systemic circulation of newborn infants with congenital left-heart
      obstruction is supplied from the right ventricle via a patent arterial duct
      between the pulmonary artery and descending aorta. The duct closes during the
      first few days of life, but infusion of prostaglandin E2 can prevent closure in
      some cases. We report four newborn infants (aged 3-8 days) with intractable heart
      failure due to severe obstruction of the left heart in the presence of a closing
      arterial duct. Infusion of prostaglandin E2 did not improve their clinical
      condition. Cardiac catheterisation and balloon dilatation of their arterial ducts
      resulted in a dramatic improvement in the babies' clinical condition; during
      subsequent surgical repair of the infants' hearts, the arterial ducts were found
      to be widely patent. Balloon dilatation gives immediate and sustained wide
      patency of the arterial duct in infants who do not respond adequately to
      prostaglandin E2.

PMID- 1346413
TI  - Toxicity of clindamycin as prophylaxis for AIDS-associated toxoplasmic
      encephalitis. Community Programs for Clinical Research on AIDS.
AB  - A double-blind, placebo-controlled trial was set up to compare clindamycin and
      pyrimethamine as prophylaxis for toxoplasmic encephalitis (TE) in HIV-infected
      patients at risk of the disorder. Interim analysis showed that clindamycin
      treated patients were 4.4 (95% confidence interval 1.3-15.2) times more likely to
      experience an adverse effect that necessitated withdrawal of the study drug than
      those who received placebo. Diarrhoea and rash were reported in 16 (31%) and 11
      (21%), respectively, of 52 patients treated with clindamycin (300 mg twice daily)
      compared with 2 (6%; p = 0.06) and none (p = 0.01) of the 32 placebo-treated
      patients. The clindamycin arm of the trial was prematurely terminated, although
      recruitment to the pyrimethamine arm continues.

PMID- 1346414
TI  - Dermatan sulphate in haemodialysis.
AB  - Experimental work suggests that dermatan sulphate has potential as an
      antithrombotic agent: it can inhibit venous thrombi yet has less effect upon
      bleeding than heparin. While heparin functions as an anticoagulant primarily by
      its ability to accelerate the action of the plasma protein inhibitor antithrombin
      III, dermatan sulphate acts selectively through a structurally related inhibitor,
      heparin co-factor II, to inhibit thrombin. We have done a series of dose-finding
      studies of the use of dermatan sulphate as an anticoagulant/antithrombotic agent
      in patients on maintenance haemodialysis. Dermatan sulphate proved to be an
      effective anticoagulant in this setting.

PMID- 1346415
TI  - Ethics and clinical research in anaesthesia.

PMID- 1346416
TI  - Cyclosporin in chronic severe asthma.

PMID- 1346417
TI  - Too tall?

PMID- 1346418
TI  - Angelchik revisited: lessons for the introduction of new operations.

PMID- 1346419
TI  - The patella.

PMID- 1346420
TI  - Epidemiology of stroke.

PMID- 1346421
TI  - Primary prevention of stroke.

PMID- 1346423
TI  - Taking heroin maintenance seriously: the politics of tolerance.

PMID- 1346422
TI  - Clinical value of polysomnography.
AB  - Polysomnography is used increasingly to investigate patients with possible sleep
      apnoea/hypopnoea syndrome (SAHS), but it has not been assessed critically. We
      thus examined prospectively the value of electrophysiological and respiratory
      monitoring in 200 consecutive adults (163 men, 37 women; mean [SD] age 50 [13]
      years) having polysomnography. At polysomnography, 91 patients had SAHS (greater
      than 15 apnoeas + hypopnoeas [A + H] per h asleep) and 11 had periodic limb
      movement disorder. Recording sleep electrophysiologically was of no diagnostic
      value and SAHS could be as accurately defined by A + H per time in bed as by A +
      H per time asleep. 66% of patients with SAHS could be diagnosed with oximetry
      alone, but many of the undiagnosed patients had moderately severe SAHS and
      benefited from treatment. Neurophysiological sleep recording is unnecessary and
      oximetry alone is of limited value in the overnight investigation of patients
      suspected of having SAHS.

PMID- 1346424
TI  - Making waves at NIH.

PMID- 1346425
TI  - Dexfenfluramine and neurotoxicity.

PMID- 1346426
TI  - Dexfenfluramine and neurotoxicity.

PMID- 1346427
TI  - Dexfenfluramine and neurotoxicity.

PMID- 1346428
TI  - Dexfenfluramine and neurotoxicity.

PMID- 1346429
TI  - Dexfenfluramine and neurotoxicity.

PMID- 1346430
TI  - Impact of vitamin A supplementation on childhood morbidity in northern Ghana.

PMID- 1346432
TI  - Increased cortical excitability in generalised epilepsy demonstrated with
      transcranial magnetic stimulation.

PMID- 1346431
TI  - Seizure induction and magnetic brain stimulation after stroke.

PMID- 1346433
TI  - Streptokinase full circle.

PMID- 1346434
TI  - Typhoid in Indonesia.

PMID- 1346435
TI  - HIV seroprevalence among women attending antenatal clinics in London.

PMID- 1346436
TI  - Vertical transmission of HIV.

PMID- 1346437
TI  - Thalidomide enantiomers.

PMID- 1346438
TI  - Nifedipine and telangiectasias.

PMID- 1346439
TI  - Familial Angelman syndrome caused by imprinted submicroscopic deletion
      encompassing GABAA receptor beta 3-subunit gene.

PMID- 1346440
TI  - Influenza and asthma.

PMID- 1346441
TI  - Influenza and asthma.

PMID- 1346442
TI  - Influenza and asthma.

PMID- 1346443
TI  - Danazol for urinary incontinence in tropical spastic paraparesis.

PMID- 1346444
TI  - Postoperative recurrence of Crohn's disease.

PMID- 1346445
TI  - Efficacy of quinine-tetracycline for acute uncomplicated falciparum malaria in
      Thailand.

PMID- 1346446
TI  - Beclomethasone and osteocalcin.

PMID- 1346447
TI  - Bone-density measurement.

PMID- 1346449
TI  - Bone-density measurement.

PMID- 1346448
TI  - Bone-density measurement.

PMID- 1346450
TI  - Badger research and human medicine.

PMID- 1346451
TI  - Female sex as an important determinant of lisinopril-induced cough.

PMID- 1346452
TI  - HCV confirmatory testing of blood donors.

PMID- 1346453
TI  - Measurement of renal blood flow by magnetic resonance angiography.

PMID- 1346454
TI  - Status epilepticus complicating intrathecal baclofen overdose.

PMID- 1346455
TI  - Liposomal amphotericin B.

PMID- 1346456
TI  - Liposomal amphotericin B.

PMID- 1346457
TI  - Microinsemination by sperm transfer.

PMID- 1346458
TI  - Control of emesis in bowel obstruction in terminally ill patients.

PMID- 1346459
TI  - Blood lead in children.

PMID- 1346460
TI  - Side-effects of octreotide withdrawal.

PMID- 1346461
TI  - SALT trial.

PMID- 1346462
TI  - SALT trial.

PMID- 1346463
TI  - Children's deaths and population growth.

PMID- 1346464
TI  - C1-esterase inhibitor substitution in sepsis.

PMID- 1346465
TI  - Beta-adrenergic agonists and hypertrophy of skeletal muscles.
AB  - Chronic administration of some beta-adrenergic agonists markedly stimulates
      hypertrophy of skeletal muscles. It appears that type II fibers are more
      responsive to beta-adrenergic agonists than type I fibers. The hypertrophic
      effect of beta-adrenergic agonists is transient, with the effect diminishing
      during prolonged treatment. Similarly, some cellular responses including the
      increase in RNA concentration and the decrease in calpain I activity are also
      short-lived. Recent evidence suggests that the temporal response is associated
      with decreased beta-adrenoceptor density. Both increased rate of protein
      synthesis and/or decreased protein degradation have been suggested as the
      mechanism of action of these compounds on hypertrophy of skeletal muscles. It is
      important to consider the temporal nature of cellular responses to chronic
      treatment of beta-adrenergic agonists as well as the differential effects of
      these compounds on protein metabolism among skeletal muscle fiber types when
      investigating the mechanism(s) of action of these compounds.

PMID- 1346467
TI  - A genetic comparison of human and wildlife isolates of Echinococcus granulosus in
      Queensland: public health implications.
AB  - OBJECTIVE: To test the hypothesis that the hydatid parasite infecting macropods
      and dingoes in Queensland is a sylvatic strain of Echinococcus granulosus,
      distinct from the domestic strain which produces cysts in sheep and humans.
      DESIGN: Molecular biological techniques were used to compare DNA isolated from
      hydatid cysts from humans, local macropods and sheep from New South Wales and the
      United Kingdom, as well as from adult tapeworms in dingoes. SETTING: The human
      cysts were surgically resected from two patients seen with hydatidosis in
      Brisbane teaching hospitals over a one-year period. Neither patient had had
      previous contact with sheep farms. Macropods and dingoes were shot randomly in
      the localities where the patients presumably acquired their infections. Sheep
      liver cysts were obtained from abattoirs. METHODOLOGY: Studies comprised
      extraction of DNA from cysts, digestion by a series of restriction endonucleases,
      slab gel electrophoresis. Southern blotting and then hybridisation with defined
      DNA probes. Polymerase chain reaction, in combination with direct DNA sequencing,
      was used to compare DNA from cysts and adult worms from dingoes. RESULTS: The
      restriction fragment length polymorphism (RFLP) patterns of DNA from all cysts
      and a defined mitochondrial DNA sequence from all sources were indistinguishable.
      This finding is significant as both techniques can clearly distinguish between
      genetically distinct, well characterised strains of E. granulosus. CONCLUSIONS:
      Hydatid cysts are prevalent in some macropod populations and adult worms are
      common in dingoes. Since there are relatively few sheep-rearing areas in
      Queensland, contact with wild animals may be the main source of human hydatid
      infection in this State. The strain of E. granulosus in both patients was
      genetically indistinguishable from that found in macropods, dingoes and sheep
      from New South Wales and the United Kingdom. This strongly suggests that the
      domestic strain of E. granulosus, or a form very close genetically, freely
      infects Australian wildlife, and argues against the existence of a distinct
      sylvatic strain. The implications for public health are considerable.

PMID- 1346466
TI  - Ethanol inhibits mitogen-induced calcium mobilization in mouse splenocytes.
AB  - Ethanol inhibited the mitogen-induced initial increase in cytoplasmic free
      calcium [Ca2+]i in mouse splenocytes. This effect was concentration-dependent,
      reversible, and observed at pharmacologically relevant concentrations (24-166mM).
      Other short-chain alcohols such as propanol, butanol, and pentanol also inhibited
      this mitogen-induced increase in [Ca2+]i. The potencies of these alcohols to
      produce this effect were highly correlated (r = 0.98, p less than 0.001) with
      their membrane/buffer partition coefficients. Analysis of mouse splenocyte
      subpopulations demonstrated that this effect was manifest in both B and T
      lymphocytes. Within T lymphocyte subpopulations, both CD4+ and CD8+ T cells were
      affected. These results suggest that the inhibition of [Ca2+]i increase may be an
      early event mediating ethanol-induced immunosuppression and that this may be a
      predisposing factor to infection and malignancies associated with alcoholism.

PMID- 1346468
TI  - Non-prescription use of bronchodilator aerosols.

PMID- 1346469
TI  - Different conformations for the same polypeptide bound to chaperones DnaK and
      GroEL.
AB  - The proteins DnaK (hsp70) and GroEL (cpn60) from Escherichia coli are prototypes
      of two classes of molecular chaperones conserved throughout evolution. The
      analysis of transferred nuclear Overhauser effects in two-dimensional NMR spectra
      is ideally suited to determine chaperone-bound conformations of peptides. The
      peptide vsv-C (amino-acid sequence KLIGVLSSLFRPK) stimulates the ATPase of BiP
      and Hsc70 (ref. 3) and the intrinsic ATPase of DnaK. The affinity of the vsv-C
      peptide for DnaK is greatly reduced in the presence of ATP. Here we analyse
      transferred nuclear Overhauser effects and show that the peptide is in an
      extended conformation while bound to DnaK but is helical when bound to GroEL. NMR
      also indicates that the mobility of the peptide backbone is reduced more by
      binding to DnaK than by binding to GroEL, whereas the side chains are less mobile
      when bound to GroEL.

PMID- 1346470
TI  - Nearly ubiquitous tissue distribution of the scrapie agent precursor protein.
AB  - The "modified host protein" model of scrapie proposes that the transmissible
      agent is composed of the degradation-resistant protein, Sp33-37, and that
      clinical and pathologic signs result from neurotoxic accumulations of this
      protein. Sp33-37 is an abnormal, amyloidogenic isoform of the normally occurring
      cellular protein Cp33-37. This study investigated the tissue distribution of Cp33
      37 in hamster. In brain, Cp33-37 was most concentrated in the hippocampal
      formation. Immunohistochemical studies localized Cp33-37 to neurons and
      surrounding neuropil in hippocampus; septal, caudate, and thalamic nuclei; dorsal
      root ganglia cells; and large-diameter dorsal root axons. In non-neuronal hamster
      tissues, Cp33-37 was detected in circulating leukocytes, heart, skeletal muscle,
      lung, intestinal tract, spleen, testis, ovary, and some other organs. The
      presence of Cp33-37 in extracerebral tissues indicates that its function is not
      unique to brain. These results indicate that the molecular substrate for the
      production of Sp33-37, the scrapie agent, and scrapie amyloid is present in a
      variety of cerebral and extracerebral sites.

PMID- 1346471
TI  - T-cell receptor alpha chain germline gene polymorphisms in multiple sclerosis.
AB  - It has been proposed that genetic predisposition to multiple sclerosis (MS) and
      other diseases with autoimmune features is conferred by T-cell receptor (TcR)
      genes in addition to HLA class II genes. Although a family study has suggested
      linkage of susceptibility to MS to TcR genes, reports of disease associations
      with restriction fragment length polymorphism (RFLP)-defined alleles of TcR genes
      have been difficult to confirm, including a report of association of MS with TcR
      beta-chain gene RFLPs. We report here the distribution of three sets of RFLPs of
      the TcR alpha chain genes. Similar frequencies in patients and controls were
      observed for TaqI and BglII RFLPs of the TcR alpha constant segment (C alpha),
      the latter earlier reported to be associated with MS. A previously reported MS
      associated PssI RFLP of the V alpha 12 and C alpha gene segments could not be
      confirmed. Our results indicate that these seemingly polymorphic restriction
      fragments are possibly the results of incomplete enzymatic cleavage of DNA in the
      RFLP analysis. We conclude that no convincing evidence exists for the association
      of MS with RFLPs of the TcR alpha or beta chain genes.

PMID- 1346472
TI  - [Prevention of carcinoid tumor crisis].
AB  - A case of the carcinoid tumour of ileum causing hormone producing multiple
      hepatic metastases was described. Sometimes after feeding and drinking of beer
      the "flush" and the diarrhoea appeared. Multiple hepatic metastases were
      established by ultrasound. Two and a half years ago the patient already was
      examined and treated by another hospital. In this time the origin of the primaer
      carcinoid tumour was not found and the superselective embolisation of the right
      lobe of the liver was made which caused a carcinoid crisis. Later the complaints
      were renewed and once more the patient was examined. The origin of the illness
      was proved in the lower ileum by CT (computer tomography), angiography and I131
      MIBG (metajod-benzyl-guanidin) scintigraphy. Another embolisation of the liver
      caused a newer carcinoid crisis. The operation of primaer carcinoid tumour was
      decided because of the danger of carcinoid crisis and ileus. In the perioperative
      period the patient was protected against carcinoid crisis by Sandostatin (made in
      SANDOZ, Basel), because the preoperative therapy, the anaesthetics and the
      surgical manipulation could have caused a carcinoid crisis. In Hungary the
      authors used for the first time somatostatin in perioperative period to protect
      the patient against carcinoid crisis.

PMID- 1346473
TI  - Glomerulopathy induced by graft-versus-host reaction in the rat. Requirement of
      donor CD4+ T lymphocytes and MHC class II incompatibility at the lymphoid
      compartment.
AB  - Graft-versus-host reactions (GVHR) can be associated with several autoimmune
      phenomena involving the kidney as a target organ. By transferring lymphocytes of
      AO rats into complete Freund's adjuvant-pretreated (AO x BN)F1 hybrids, a dose
      dependent GVHR with glomerulopathy was experimentally induced. IgM, IgG1, and
      IgG2a were deposited in the mesangial area and along the glomerular basement
      membrane. Eluted immunoglobulins from diseased kidneys bound to normal basement
      membranes and especially to laminin. Anti-laminin reactivity was also present in
      sera from F1 recipients with GVHR. Parental CD4+ T lymphocytes were required and
      sufficient to induce GVHR and glomerulopathy in sublethally irradiated F1
      hybrids. Using various F1 hybrids, MHC class II incompatibility was shown to be
      required for the induction of GVHR-associated glomerulopathy. Across MHC class I
      incompatibility, GVHR without glomerulopathy could be induced, provided that both
      CD4+ and CD8+ donor T lymphocytes were administered. Finally, MHC incompatibility
      between donor T lymphocytes and the recipient non-lymphoid compartment was found
      to be sufficient for the induction of GVHR, but not for GVHR-associated
      glomerulopathy. The results indicate that alloreactive donor CD4+ T lymphocytes
      have to interact directly with MHC class II alloantigen bearing host B
      lymphocytes in order to stimulate the latter to produce (auto-)antibodies. GVHR
      induced glomerulopathy shares several immunopathological features with HgCl2
      induced autoimmune glomerulopathy in the rat.

PMID- 1346474
TI  - Trends in parasitology. Living together.

PMID- 1346475
TI  - Homeobox genes go evolutionary.

PMID- 1346476
TI  - Modulation of activity of the promoter of the human MDR1 gene by Ras and p53.
AB  - Drug resistance in human cancer is associated with overexpression of the
      multidrug resistance (MDR1) gene, which confers cross-resistance to hydrophobic
      natural product cytotoxic drugs. Expression of the MDR1 gene can occur de novo in
      human cancers in the absence of drug treatment. The promoter of the human MDR1
      gene was shown to be a target for the c-Ha-Ras-1 oncogene and the p53 tumor
      suppressor gene products, both of which are associated with tumor progression.
      The stimulatory effect of c-Ha-Ras-1 was not specific for the MDR1 promoter
      alone, whereas a mutant p53 specifically stimulated the MDR1 promoter and wild
      type p53 exerted specific repression. These results imply that the MDR1 gene
      could be activated during tumor progression associated with mutations in Ras and
      p53.

PMID- 1346477
TI  - High probability opening of NMDA receptor channels by L-glutamate.
AB  - Synaptic plasticity can be triggered by calcium flux into neurons through
      synaptically activated N-methyl-D-aspartate (NMDA) receptor channels. The
      amplitude and time course of the resulting intracellular calcium transient depend
      on the number of open NMDA receptor channels and the kinetics of their
      activation. Short applications of L-glutamate to outside-out patches from
      hippocampal neurons in the presence and absence of MK-801 revealed that about 30
      percent of L-glutamate-bound channels are open at the peak of the current. This
      high probability of opening suggests that very few channels are required to
      guarantee a large, localized postsynaptic calcium transient.

PMID- 1346478
TI  - New trends in treating chronic persistent asthma in adults.

PMID- 1346479
TI  - Beta-blockers in prevention of variceal hemorrhage: tantalizing expectations.

PMID- 1346480
TI  - Impaired Helicobacter pylori urease enzyme activity by histamine 2 receptor
      antagonist.

PMID- 1346481
TI  - Familial recurrence-pattern analysis of cleft lip with or without cleft palate.
AB  - Cleft lip with or without cleft palate (CL/P) is a common congenital malformation
      with an incidence in European white populations of about 1/1,000. The familial
      clustering of CL/P has been extensively characterized, and epidemiological
      studies have proposed monogenic models (with reduced penetrance),
      multifactorial/threshold models, and mixed major-gene/multifactorial models to
      explain its inheritance. The recognition of an association between two RFLPs at
      the transforming growth factor alpha (TGFA) locus and CL/P supports a major-gene
      component to the etiology of CL/P. Risch has shown that the recurrence risk ratio
      lambda R (risk to relatives, vs. population prevalence) is a useful pointer to
      the mode of inheritance. Here we further develop the use of lambda R to analyze
      recurrence-risk data for CL/P. Recurrence risks for first-, second-, and third
      degree relatives equate well with oligogenic models with as few as four loci. A
      monogenic/additive model is strongly rejected. The limited available twin data
      are also consistent with this model. A "major gene" interacting epistatically
      with an oligogenic background is shown to be a plausible alternative. Power
      calculations for a linkage study to map the CL/P major-risk locus suggest that a
      sample of 50 affected sib pairs will be adequate, but linkage to minor-risk loci
      will require very much larger samples.

PMID- 1346482
TI  - Isolation and characterization of new highly polymorphic DNA markers from the
      Huntington disease region.
AB  - The defect causing Huntington disease (HD) has been mapped to 4p16.3, distal to
      the DNA marker D4S10. Subsequently, additional polymorphic markers closer to the
      HD gene have been isolated, which has led to the establishment of predictive
      testing programs for individuals at risk for HD. Approximately 17% of persons
      presenting to the Canadian collaborative study for predictive testing for HD have
      not received any modification of risk, in part because of limited informativeness
      of currently available DNA markers. Therefore, more highly polymorphic DNA
      markers are needed, which will further increase the accuracy and availability of
      predictive testing, specifically for families with complex or incomplete pedigree
      structures. In addition, new markers are urgently needed in order to refine the
      breakpoints in the few known recombinant HD chromosomes, which could allow a more
      accurate localization of the HD gene within 4p16.3 and, therefore, accelerate the
      cloning of the disease gene. In this study we present the identification and
      characterization of nine new polymorphic DNA markers, including three markers
      which detect highly informative multiallelic VNTR-like polymorphisms with PIC
      values of up to .84. These markers have been isolated from a cloned region of DNA
      which has been previously mapped approximately 1,000 kb from the 4p telomere.

PMID- 1346483
TI  - Factor IXMadrid 2: a deletion/insertion in factor IX gene which abolishes the
      sequence of the donor junction at the exon IV-intron d splice site.
AB  - DNA from a patient with severe hemophilia B was evaluated by RFLP analysis,
      producing results which suggested the existence of a partial deletion within the
      factor IX gene. The deletion was further localized and characterized by PCR
      amplification and sequencing. The altered allele has a 4,442-bp deletion which
      removes both the donor splice site located at the 5' end of intron d and the two
      last coding nucleotides located at the 3' end of exon IV in the normal factor IX
      gene; this fragment has been replaced by a 47-bp sequence from the normal factor
      IX gene, although this fragment has been inserted in inverted orientation. Two
      homologous sequences have been discovered at the ends of the deleted DNA
      fragment.

PMID- 1346485
TI  - Alcohol abuse, substance abuse, and panic disorder.
AB  - The purpose of this article is to review the literature concerning the
      interaction of alcohol and/or substance abuse with panic disorder, the
      comorbidity of these disorders, possible causal relationships, biologic
      relationships, and the recognition and treatment of dually disordered patients. A
      number of studies suggest significant comorbidity between panic disorder and
      alcoholism or abuse of drugs, especially cocaine and sedatives. Panic may lead to
      drinking or sedative use and also result from prolonged use or withdrawal of
      alcohol or other drugs. Possible biologic relationships involve the gamma
      aminobutyric acid (GABA)-benzodiazepine receptor complex and the central
      noradrenergic system. Although treatment of panic in substance abusers has not
      been studied specifically, guidelines for recognition and management of these
      patients, including use of antipanic medication, are discussed.

PMID- 1346484
TI  - Integrated treatment of panic disorder.
AB  - The purpose of this article is to provide the nonpsychiatric physician with a
      practical approach to the treatment of panic disorder by reviewing the literature
      on treatment efficacy. The author reviews studies and uncontrolled case series on
      pharmacologic and nonpharmacologic treatment of panic disorder and presents a
      clinical approach based on these. Setting the stage for treatment by educating
      patients and obtaining a detailed description of their particular clinical
      syndrome is a vital, but frequently neglected, precursor to treatment. Treatment
      selection is based on a risk-benefit analysis of the individual treatment and the
      particular exigencies of the patient's clinical presentation. Both pharmacologic
      and nonpharmacologic therapies are highly effective for acute treatment. Because
      panic disorder is a chronic illness, long-term treatment or reinitiation of acute
      treatment at a later date is often required.

PMID- 1346486
TI  - Lack of association between dopamine D1 and D2 receptor genes and bipolar
      affective disorder.
AB  - Fifty-six patients with bipolar affective disorder and 69 healthy control
      subjects were tested for association of restriction fragment length polymorphism
      alleles at the dopamine D1 and D2 receptor loci. No significant associations were
      found; thus, the hypothesis that a single mutant form of either receptor gene is
      responsible for the phenotype of patients with bipolar affective disorder was not
      supported.

PMID- 1346487
TI  - Cardiovascular function during induced hypotension by fenoldopam or sodium
      nitroprusside in anesthetized dogs.
AB  - Fenoldopam, a selective dopamine1 receptor agonist, has been recommended for
      induced hypotension because it effectively lowers arterial blood pressure and
      improves renal perfusion. We examined cardiovascular functions during hypotension
      induced by fenoldopam or sodium nitroprusside. In eight halothane-anesthetized
      dogs, the left ventricle (LV) was instrumented with pressure and ultrasonic
      dimension transducers for the assessment of LV contractility using the analysis
      of the pressure-diameter relationship. Blood flow distribution was measured by
      radioactive microspheres. Doses of fenoldopam and nitroprusside were titrated to
      reduce mean arterial blood pressure to 60 mm Hg. After 40 min of hypotension,
      fenoldopam and nitroprusside caused similar increases in heart rate (17% +/- 4%
      vs 19% +/- 10%, respectively) and decreases in systemic vascular resistance (-24%
      +/- 5% vs -27% +/- 4%). Hypotension induced by fenoldopam was associated with
      higher LV end-diastolic pressure (4.4 +/- 0.6 vs 2.5 +/- 1.1 mm Hg) and end
      systolic meridional wall stress (33.0 +/- 4.3 vs 17.8 +/- 2.1 g/cm2) when
      compared with nitroprusside. There were no significant changes in cardiac output
      and cardiac contractility as expressed by the slope (Ees) of the LV end-systolic
      pressure-diameter relationship, velocity of shortening of the diameter, and
      percentage of wall thickening of the LV. In contrast to nitroprusside, which
      decreased renal blood flow from 197 +/- 19 to 163 +/- 15 mL/min, renal blood flow
      increased during fenoldopam-induced hypotension from 187 +/- 20 to 239 +/- 18
      mL/min. The increase in renal perfusion was similar in upper, middle, and lower
      regions of the kidney; however, it was more in the medulla compared with the
      cortex (37% +/- 17% vs 25% +/- 7%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346488
TI  - Airway inflammation in asthma. The Proceedings of a Roundtable discussion, July
      1990.

PMID- 1346489
TI  - "Helper" (CD4+) T cells and eosinophils in allergy and asthma.

PMID- 1346490
TI  - Expression and amplification of neu oncogene in pleomorphic adenomas of salivary
      gland.
AB  - Amplification of the neu oncogene and overexpression of its product was found to
      be a potential marker for aggressive biological behavior in breast cancer.
      However, the expression of the neu oncoprotein in normal breast ducts and
      myoepithelial cells has also been demonstrated. Hence, we examined normal
      salivary gland tissue and 15 cases of pleomorphic adenoma for the expression of
      the neu oncoprotein by immunohistochemistry using two polyclonal antibodies and
      12 cases for the amplification of the neu oncogene using slot blot hybridization.
      Immunohistochemistry in the normal salivary gland revealed positive staining of
      all ductal cells. In the pleomorphic adenomas all cellular elements stained to a
      variable degree. The positive staining was seen in the ductal cells, in the solid
      sheets, and in chondroid, myxoid, and metaplastic foci. The normal salivary gland
      and 11 of 12 cases of pleomorphic adenoma showed no increase in copy number of
      the neu oncogene, whereas one case showed threefold amplification. These results
      indicate that the neu oncoprotein is expressed but the neu copy number is not
      increased in normal salivary gland epithelium and in most pleomorphic adenomas.
      The threefold amplification of the gene in one case may indicate an aggressive
      biological behavior.

PMID- 1346491
TI  - Somatostatin in the management of gastrointestinal fistulas. A multicenter trial.
AB  - To evaluate the effectiveness of treatment with total parenteral nutrition (TPN)
      alone (group A) or combined with continuous intravenous infusion of somatostatin
      (group B) in postoperative gastrointestinal fistulas, a multicenter, controlled
      and prospective randomized trial was designed. We present the results obtained
      after the evaluation of 40 cases (group A, n = 20; group B, n = 20). No
      significant differences among these treatment schedules were observed in the
      percentage of closure of fistulas (group A, 81.25%; group B, 85%), but patients
      treated with total parenteral nutrition plus somatostatin had the fistulas close
      within a significantly shorter period of time. Moreover, this treatment was
      associated with a significantly lower morbidity. These preliminary results
      indicate that somatostatin is a useful therapeutic complement in the conservative
      treatment of patients with gastrointestinal fistulas.

PMID- 1346492
TI  - Congenitally defective aldosterone biosynthesis in humans: the involvement of
      point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients.
AB  - The gene for steroid 18-hydroxylase (P-450C18) has been recently assigned to
      encode corticosterone methyl oxidases Type I and Type II which were previously
      postulated to catalyze the final two steps in the biosynthesis of aldosterone in
      humans. Molecular genetic analysis of the P-450C18 gene is three patients from
      three different families affected with CMO II deficiency has indicated that a
      point mutation of CGG----TGG (181Arg----Trp) in exon 3 and one of GTG----GCG
      (386Val----Ala) in exon 7 occur exclusively in the gene of the patients. Analysis
      of PCR products by restriction enzymes (HapII and HphI) has indicated that the
      patients are homozygous and the unaffected parent is heterozygous for both
      mutations, in accordance with the established concept that CMO II deficiency is
      inherited in an autosomal recessive manner. These data clearly provide the
      molecular genetic basis for the characteristic biochemical phenotype of CMO II
      clinical variants.

PMID- 1346493
TI  - Rational design and pre-clinical pharmacology of drugs for reversing multidrug
      resistance.
AB  - Drugs that interfere with the action of P-glycoprotein (P-gp), the membrane
      efflux pump responsible for multidrug resistance (MDR), should be valuable in the
      treatment of patients with drug-resistant cancer. We have used one class of drug,
      the phenothiazines, to study the structural features required for optimum
      interference with the function of P-gp. The structure-activity relationships
      revealed three important components including the hydrophobicity of the tricyclic
      ring, the length of the alkyl bridge and the charge on the terminal amino group.
      Trans-flupenthixol is a lead compound that conforms to these structural
      requirements and demonstrates significant activity as a sensitizer of MDR cell
      lines to drugs affected by the MDR phenotype. Based on these data, we have
      proposed a model for the binding of modulators to P-gp and have speculated on the
      structure of the drug-binding domain. We have developed pre-clinical models of
      MDR that may help predict clinical activity of chemo-modulators. L1210/VMDRC.06
      is a murine lymphocytic leukemia line transformed by a retroviral expression
      vector containing a full-length cDNA for the human mdr1 gene. K562/VBL1-3 are
      clones of human myeloid blast cells that were transformed with the same vector.
      Resistance in these lines is not complicated by changes in the cellular content
      of glutathione or alterations in topoisomerase II. The transformed L1210 line
      grows in mice as a slowly proliferating non-metastatic peritoneal implant. Both
      MDR lines are restored to sensitivity by cyclosporin A or trans-flupenthixol, and
      the K562 clones are induced to differentiate by hemin. These lines should provide
      simple, sensitive screens for new drugs for use against cancers expressing P-gp.
      We have proposed a model to explain how the pumping activity of P-gp is activated
      in response to toxic drugs. In this schema, basal activity of P-gp is modulated
      through phosphorylation/dephosphorylation reactions mediated by protein kinase C
      (PKC) and calcium sensitive phosphatases. In response to the activation of
      phospholipase C by toxic drugs and the local production of 1,2-diacylglycerol,
      PKC is translocated to the cell membrane where it phosphorylates P-gp. Following
      the extrusion of drug from the cell membrane, phospholipase C activity returns to
      baseline, diacylglycerol is metabolized, PKC returns to the cytosol and
      serine/threonine phosphatases dephosphorylate P-gp returning it to the basal
      state.

PMID- 1346494
TI  - Cyclosporins as drug resistance modifiers.
AB  - Cyclosporin A (CsA), a cyclic peptide of 11 amino acids isolated from the fungus
      Tolypoclodium inflatum Gams, is the principle drug used for immunosuppression in
      organ transplant patients. It is known to have a very specific effect on T-cell
      proliferation although the precise mechanism remains unclear. Following
      internalization, CsA binds to a cytosolic protein, cyclophilin, which has been
      shown to possess peptidyl-prolyl cis-trans isomerase activity. CsA is an
      effective modifier of multidrug resistance in human and rodent cells at doses in
      the range of 1 to 5 micrograms/mL. Although it reverses the drug accumulation
      deficit associated with multidrug resistance in some cell types, this is not
      always the case. CsA has P-glycoprotein binding activity but less specific
      membrane effects and inhibition of protein kinase C may also be involved in its
      resistance modifier action. A number of non-immunosuppressive analogues of CsA
      have been shown to have resistance modifier activity and some are more potent
      than the parent compound. One analogue from Sandoz, PSC-833, has been shown to be
      approximately 10-fold more potent than CsA and is expected to enter clinical
      trial in the near future. The use of such agents may allow a full test of the
      hypothesis that reversal of multidrug resistance will prove a useful clinical
      strategy.

PMID- 1346495
TI  - Biochemical and genetic characterization of the multidrug resistance phenotype in
      murine macrophage-like J774.2 cells.
AB  - The development of multidrug resistance (MDR) in malignant tumors is a major
      obstacle to the treatment of many cancers. MDR sublines have been derived from
      the J774.2 mouse macrophage-like cell line and utilized to characterize the
      phenotype at the biochemical and genetic level. Two isoforms of the drug
      resistance-associated P-glycoprotein are present and distinguishable both
      electrophoretically and pharmacologically. Genetic analysis has revealed the
      presence of a three-member gene family; expression of two of these genes, mdr1a
      and mdr1b, is associated with MDR whereas the expression of the third, mdr2, is
      not. Studies of these three genes have revealed similarities and differences in
      the manner in which they are regulated at the transcriptional level, and have
      suggested that post-transcriptional effects may also be important.

PMID- 1346496
TI  - Photoaffinity substrates for P-glycoprotein.
AB  - A variety of compounds can inhibit the function of P-glycoprotein (Pgp) by
      binding to it and preventing the efflux of anticancer drug substrates. While the
      molecular architecture of the drug binding site(s) in Pgp is not known, it is
      clear that modulators in general appear to conform to some general physical
      chemical rules. In this paper, we discuss the basic concepts of drug recognition
      by Pgp as currently understood. We also examine the compounds used to
      photoaffinity label this protein and discuss their utility in identifying drug
      binding sites. Finally, we show that a photoaffinity analog of daunorubicin,
      [3H]azidobenzoyl-daunorubicin ([3H]AB-DNR), is a good affinity labeling reagent
      for Pgp. A finding of interest is that vinblastine and verapamil compete more
      effectively than daunorubicin for [3H]AB-DNR binding to Pgp, suggesting that
      vinblastine and verapamil have similar structural features not shared by
      daunorubicin.

PMID- 1346497
TI  - The role of the MDR1 (P-glycoprotein) gene in multidrug resistance in vitro and
      in vivo.
AB  - This review describes the studies that address the role of the MDR1 (P
      glycoprotein) gene in multidrug resistance in cell lines selected in vitro and in
      clinical cancer. Molecular genetic studies have demonstrated that expression of P
      glycoprotein, an efflux pump acting at diverse lipophilic compounds, is
      sufficient to provide resistance to a large number of lipophilic drugs in tissue
      culture. The MDR1 gene is expressed in several normal human tissues associated
      with secretory or barrier functions and in some bone marrow and blood cells,
      including hematopoietic progenitor cells. MDR1 expression in clinical cancer is
      often found in untreated tumors of different types. Several studies showed a
      correlation between MDR1 expression and tumor resistance to combination
      chemotherapy. MDR1 expression in untreated tumors may reflect their origin from
      MDR1-positive normal cells or cellular changes associated with neoplastic
      transformation or progression. MDR1 expression in some types of cancer may be a
      marker of a more aggressive subpopulation of tumor cells, possessing multiple
      mechanisms for resistance to treatment.

PMID- 1346498
TI  - Linkage between rheumatoid arthritis susceptibility and the presence of HLA-DR4
      and DR beta allelic third hypervariable region sequences in southern Chinese
      persons.
AB  - OBJECTIVE: To analyze HLA-DR and DQ associations with rheumatoid arthritis (RA)
      in patients from southern China. METHODS: In 66 patients and 45 controls,
      restriction fragment length polymorphism studies were performed using DRB, DQA,
      and DQB probes, and DRB allele-specific typing of polymerase chain reaction
      amplified DRB DNA: RESULTS: The frequency of HLA-DR4 was significantly increased
      among RA patients (42.4% versus 17.8%). Increased frequencies of the DQA3 allele
      (77.8% versus 48.9%) and the DQB1*0302 allele (71.0% versus 46.3%), which are in
      linkage disequilibrium with DR4, were also found. Oligonucleotide typing showed
      that the amino acid sequence LLEQRRAA, spanning amino acid positions 67-74 of the
      DR beta molecule, was found in 19 of 49 patients and 5 of 32 controls. The main
      DR4 allelic subtypes found in the population were DRB1*0404 and DRB1*0405, both
      of which carried the sequence. There was no difference in subtype distribution
      between patients and controls. CONCLUSION: Chinese RA patients have an increased
      frequency of HLA-DR4 alleles which possess the same DRB third allelic
      hypervariable sequence shown to be associated with susceptibility in Caucasian RA
      patients.

PMID- 1346500
TI  - Amplification of reproducible allele markers for amplified fragment length
      polymorphism analysis.
AB  - A procedure for amplification by PCR of reproducible allele markers for amplified
      fragment length polymorphism (Amp-FLP) analysis is presented. We have prepared
      markers for the allelic products of the VNTR loci D1S80 (MCT118) and D17S30
      (YNZ22) and for the hypervariable VNTR locus close to the 3' end of the
      apolipoprotein B gene (apoB) by re-amplifying a mixture of PCR products from
      individuals with known alleles. These allele markers allow precise and discrete
      determination of the VNTR alleles at these loci using the Amp-FLP technique that
      should prove suitable in forensic analyses, paternity testing and population
      studies.

PMID- 1346499
TI  - Lack of superiority of steroids plus plasma exchange to steroids alone in the
      treatment of polyarteritis nodosa and Churg-Strauss syndrome. A prospective,
      randomized trial in 78 patients.
AB  - OBJECTIVE: To define the most effective treatment for polyarteritis nodosa (PAN)
      and Churg-Strauss syndrome (CSS). METHODS: We conducted a prospective,
      randomized, multicenter trial in which 78 patients were randomly assigned to
      receive either prednisone and plasma exchange (group A; n = 36) or prednisone
      alone (group B; n = 42) as first-line treatment of PAN and CSS. Patients with
      hepatitis B virus-related PAN were not included in this study. The end point of
      the study was control of the disease (recovery and remission) or death. RESULTS:
      Clinical symptoms and laboratory findings did not differ statistically in the 2
      groups at study entry. Initial control of the disease was similar in both groups.
      The assigned treatment was stopped in 16 patients because of lack of efficacy.
      Oral cyclophosphamide or dapsone therapy reversed the disease evolution in 7 of
      these 10 group A patients and in 4 of these 6 group B patients. At 7 years of
      followup, 56 patients had completely recovered (27 in group A, 29 in group B), 7
      patients were in clinical remission, and 15 patients had died (19.2%; 6 group A
      patients and 9 group B patients). The prednisone-plasma exchange combination was
      no more beneficial than corticosteroids alone in preventing relapses over the
      long term. There was no significant difference in the 7-year cumulative survival
      rates of the two groups (83% and 79%, respectively). CONCLUSION: Based on our
      data, we conclude that combined treatment with prednisone and plasma exchange is
      not superior to treatment with prednisone alone and must not be systematically
      employed for initial treatment of PAN and CSS. In most cases, cyclophosphamide as
      second-line treatment is effective and well tolerated.

PMID- 1346501
TI  - Abstracts of the VIth Biennial European Workshop on Schizophrenia. Badgastein,
      Austria, January 26-31, 1992.

PMID- 1346502
TI  - Substitution of glutamic acid 109 by aspartic acid alters the substrate
      specificity and catalytic activity of the beta-subunit in the tryptophan synthase
      bienzyme complex from Salmonella typhimurium.
AB  - In an effort to understand the catalytic mechanism of the tryptophan synthase
      beta-subunit from Salmonella typhimurium, possible functional active site
      residues have been identified (on the basis of the 3-D crystal structure of the
      bienzyme complex) and targeted for analysis utilizing site-directed mutagenesis.
      The chromophoric properties of the pyridoxal 5'-phosphate cofactor provide a
      particularly convenient and sensitive spectral probe to directly investigate
      changes in catalytic events which occur upon modification of the beta-subunit.
      Substitution of Asp for Glu 109 in the beta-subunit was found to alter both the
      catalytic activity and the substrate specificity of the beta-reaction. Steady
      state kinetic data reveal that the beta-reaction catalyzed by the beta E109D
      alpha 2 beta 2 mutant enzyme complex is reduced 27-fold compared to the wild-type
      enzyme. Rapid-scanning stopped-flow (RSSF) UV-visible spectroscopy shows that the
      mutation does not seriously affect the pre-steady-state reaction of the beta
      E109D mutant with L-serine to form the alpha-aminoacrylate intermediate, E(A-A).
      Binding of the alpha-subunit specific ligand, alpha-glycerol phosphate (GP) to
      the alpha 2 beta 2 complex exerts the same allosteric effects on the beta-subunit
      as observed with the wild-type enzyme. However, the pre-steady-state spectral
      changes for the reaction of indole with E(A-A) show that the formation of the L
      tryptophan quinonoid, E(Q3), is drastically altered. Discrimination against E(Q3)
      formation is also observed for the binding of L-tryptophan to the mutant alpha 2
      beta 2 complex in the reverse reaction. In contrast, substitution of Asp for Glu
      109 increases the apparent affinity of the beta E109D alpha-aminoacrylate complex
      for the indole analogue indoline and results in the increased rate of synthesis
      of the amino acid product dihydroiso-L-tryptophan. Thus, the mutation affects the
      covalent bond forming addition reactions and the nucleophile specificity of the
      beta-reaction catalyzed by the bienzyme complex.

PMID- 1346503
TI  - The International Society for Heart and Lung Transplantation, twelfth annual
      meeting and scientific session. April 2-4, 1992, San Diego, California.
      Abstracts.

PMID- 1346504
TI  - European Association of Cardiothoracic Anaesthesiologists, sixth annual meeting.
      Milano, Italy, June 4-7, 1991. Abstracts.

PMID- 1346505
TI  - Double blind dose-response study of zidovudine in AIDS and advanced HIV
      infection. Nordic Medical Research Councils' HIV Therapy Group.
AB  - OBJECTIVE: To compare the efficacy and side effects of 400 mg, 800 mg, and 1200
      mg zidovudine daily in patients with AIDS or advanced HIV infection. DESIGN:
      Randomised, double blind, parallel group multicentre study. SETTING: Hospital
      departments of infectious diseases and dermatology in Denmark, Sweden, Norway,
      Finland, and Iceland. SUBJECTS: 474 patients: 126 (27%) with AIDS; 248 (52%) with
      HIV related symptoms; 100 (21%) with low CD4+ cell counts. INTERVENTIONS:
      Zidovudine 400 mg (160 patients), 800 mg (158), or 1200 mg (156) daily. All
      patients received one capsule from each of three bottles four times daily. MAIN
      OUTCOME MEASURES: Survival; incidence of new HIV related events; CD4+ cell count;
      quality of life; incidence of haematological side effects. RESULTS: 460 (97%) of
      the 474 patients had not received zidovudine previously. The median follow up
      period was 19 months, during which the death rates in the three treatment groups
      were 23% (36/160 patients), 23% (36/158), and 19% (30/156) respectively (p =
      0.49; log rank test). One year after the trial was terminated the death rates
      were 38% (61/160), 41% (64/158), and 44% (68/156) respectively (p = 0.54). There
      was no significant difference between the groups in time to a new AIDS defining
      event or death, average number of events per patient, decline in CD4+ cell
      counts, wellbeing (visual analogue scale), or Karnofsky score. Zidovudine was
      withdrawn in 132 (28%) patients, mainly because of side effects (71 cases; 15%).
      The incidences of anaemia and leucopenia, time to first dose reduction, and
      numbers of patients withdrawn were all dose related. CONCLUSION: Zidovudine
      should be limited to 400-600 mg daily in patients with AIDS or advanced HIV
      infection.

PMID- 1346506
TI  - Aminergic neurons in the brain of blowflies and Drosophila: dopamine- and
      tyrosine hydroxylase-immunoreactive neurons and their relationship with putative
      histaminergic neurons.
AB  - The distribution and morphology of neurons reacting with antisera against
      dopamine (DA), tyrosine hydroxylase (TH) and histamine (HA) were analyzed in the
      blowflies Calliphora erythrocephala and Phormia terraenovae. TH-immunoreactive
      (THIR) and HA-immunoreactive (HAIR) neurons were also mapped in the fruitfly
      Drosophila melanogaster. The antisera against DA and TH specifically labeled the
      same neurons in the blowflies. About 300 neurons displayed DA immunoreactivity
      (DAIR) and THIR in the brain and subesophageal ganglion of the blowflies. Most of
      these neurons were located in bilateral clusters; some were distributed as
      bilateral pairs, and two ventral unpaired median (VUM) neurons were seen in the
      subesophageal ganglion. Immunoreactive processes were found in all compartments
      of the mushroom bodies except the calyces, in all divisions of the central body
      complex, in the medulla, lobula and lobula plate of the optic lobe, and in non
      glomerular neuropil of protocerebrum, tritocerebrum and the subesophageal
      ganglion. No DA or TH immunoreactivity was seen in the antennal lobes. In
      Drosophila, neurons homologous to the blowfly neurons were detected with the TH
      antiserum. In Phormia and Drosophila, 18 HA-immunoreactive neurons were located
      in the protocerebrum and 2 in the subesophageal ganglion. The HAIR neurons
      arborized extensively, but except for processes in the lobula, all HAIR processes
      were seen in non-glomerular neuropil. The deuto- and tritocerebrum was devoid of
      HAIR processes. Double labeling experiments demonstrated that TH and HA
      immunoreactivity was not colocalized in any neuron. In some regions there was,
      however, substantial superposition between the two systems. The morphology of the
      extensively arborizing aminergic neurons described suggests that they have
      modulatory functions in the brain and subesophageal ganglion.

PMID- 1346508
TI  - Dose-dependent modulation of the cardiac sodium channel by sea anemone toxin
      ATXII.
AB  - The effects of sea anemone toxin ATXII on single sodium channels were studied in
      cell-attached patches on rabbit ventricular myocytes at 20-22 degrees C. Exposure
      of patches to 1,000 nM ATXII induced long-lasting bursts of openings, which were
      more dramatically different from control at -20 mV than at -50 mV. Mean open
      duration, which had a biphasic dependence on voltage in control patches, was
      monotonically dependent on voltage in toxin-exposed patches, being 3.5 times
      longer than control at -20 mV and 4.5 times longer at -10 mV. Multiple mean open
      durations were detected at depolarized potentials. To test whether the multiple
      mean open durations resulted from a mixture of modified and unmodified openings,
      histograms of late openings (when unmodified channels would be inactivated) were
      constructed. Because in most cases these fit a single exponential with a mean
      open duration like that of modified channels, we conclude that voltage-dependent
      toxin unbinding produced a mixed population of unmodified and modified openings.
      Consistent with this hypothesis, lower concentrations of toxin most often
      produced open-duration histograms best fit with two exponentials. Ensembles
      revealed complex decay kinetics, which could be interpreted within the context of
      the toxin-induced increase in mean open duration and burst duration and the
      summation of modified and unmodified events. Analysis of the numbers of early
      versus late events at -20 mV for patches exposed to 20 nM, 100 nM, and 1,000 nM
      ATXII predicted the ED50 for ATXII block to be 285 nM at this potential. Using a
      five-state Markovian model, the action of ATXII could be explained as a reduction
      of the open-to-inactivated rate constant without effect on inactivation from
      closed states or other rate transitions.

PMID- 1346509
TI  - The effects of acute and chronic cocaine use on the heart.
AB  - It is clear that cocaine has cardiotoxic effects. Acute doses of cocaine suppress
      myocardial contractility, reduce coronary caliber and coronary blood flow, induce
      electrical abnormalities in the heart, and in conscious preparations increase
      heart rate and blood pressure. These effects will decrease myocardial oxygen
      supply and may increase demand (if heart rate and blood pressure rise). Thus,
      myocardial ischemia and/or infarction may occur, the latter leading to large
      areas of confluent necrosis. Increased platelet aggregability may contribute to
      ischemia and/or infarction. Young patients who present with acute myocardial
      infarction, especially without other risk factors, should be questioned regarding
      use of cocaine. As recently pointed out by Cregler, cocaine is a new and
      sometimes unrecognized risk factor for heart disease. Acute depression of LV
      function by cocaine may lead to the presence of a transient cardiomyopathic
      presentation. Chronic cocaine use can lead to the above problems as well as to
      acceleration of atherosclerosis. Direct toxic effects on the myocardium have been
      suggested, including scattered foci of myocyte necrosis (and in some but not all
      studies, contraction band necrosis), myocarditis, and foci of myocyte fibrosis.
      These abnormalities may lead to cases of cardiomyopathy. Left ventricular
      hypertrophy associated with chronic cocaine recently has been described.
      Arrhythmias and sudden death may be observed in acute or chronic use of cocaine.
      Miscellaneous cardiovascular abnormalities include ruptured aorta and
      endocarditis. Most of the cardiac toxicity with cocaine can be traced to two
      basic mechanisms: one is its ability to block sodium channels, leading to a local
      anesthetic or membrane-stabilizing effect; the second is its ability to block
      reuptake of catecholamines in the presynaptic neurons in the central and
      peripheral nervous system, resulting in increased sympathetic output and
      increased catecholamines. Other potential mechanisms of cocaine cardiotoxicity
      include a possible direct calcium effect leading to contraction of vessels and
      contraction bands in myocytes, hypersensitivity, and increased platelet
      aggregation (which may be related to increased catecholamine). The correct
      therapy for cocaine cardiotoxicity is not known. Calcium blockers, alpha
      blockers, nitrates, and thrombolytic therapy show some promise for acute
      toxicity. Beta-Blockade is controversial and may worsen coronary blood flow. In
      patients who develop cardiomyopathy, the usual therapy for this entity is
      appropriate.

PMID- 1346507
TI  - Light- and electron-microscopic studies of the somatostatin-immunoreactive plexus
      in the cat retina.
AB  - Two monoclonal antibodies directed against somatostatin 14 were used to study
      immunoreactive neurons, their processes and their synapses in the cat retina. In
      retinal whole-mounts, a sparse population of wide-field displaced amacrine cells
      was observed predominantly in the ventral retina and near the retinal margin.
      Processes of these cells ramified mainly in two distinct strata within the inner
      plexiform layer: one near the inner nuclear layer (INL), and the other near the
      ganglion cell layer (GCL). The length of immunoreactive fibres within each plexus
      was measured: 232 +/- 32 mm/mm2 near the INL and 230 +/- 74 mm/mm2 near the GCL
      in all retinal regions. The immunoreactive processes were studied using electron
      microscopic techniques; conventional and some ribbon-containing synapses
      ("dyads") were found. Immunolabelled processes received input synapses from other
      amacrine cell processes. These investigations provide further evidence that this
      cell population has a diffuse, regulatory or modulatory role for visual
      information processing in the inner plexiform layer.

PMID- 1346510
TI  - Elevated endothelin-1 in heart failure and loss of normal response to postural
      change.
AB  - BACKGROUND: The possible contribution of endothelin-1, a potent endothelium
      derived vasoconstrictor peptide, to neurohumoral compensation for hemodynamic
      stress was examined in nine normal volunteers and six patients with severe
      congestive heart failure. METHODS AND RESULTS: Plasma levels of endothelin-1 were
      measured with a sensitive and specific radioimmunoassay. Venous blood samples
      were obtained after 90 minutes of supine rest and serially during 30 minutes of
      60 degrees upright tilt. Endothelin-1 levels were compared with those of known
      neurohumoral mediators of compensation. In normal subjects, the resting levels of
      endothelin-1 were low (0.74 +/- 0.11 pg/ml), and there was a rapid increase to
      1.37 +/- 0.07 pg/ml at 5 minutes of upright tilting (p less than 0.05). This
      increase was not sustained at 10 and 15 minutes of tilt, but there was a trend
      toward a second rise at 30 minutes (1.14 +/- 0.17 pg/ml; p = 0.06). This biphasic
      pattern of response was shared by dopamine and reflected the response of systemic
      blood pressure to postural change. In contrast, slower and more sustained
      increases in circulating levels were observed for norepinephrine, epinephrine,
      aldosterone, plasma renin activity, and vasopressin, whereas atrial natriuretic
      peptide tended to decrease progressively. Patients with congestive heart failure
      had markedly higher basal levels of circulating endothelin-1 than normal subjects
      (3.7 +/- 0.5 pg/ml; p less than 0.01), and there was no further increase on
      postural change. Similar patterns were observed for the other neurohumoral
      mediators measured, with the degree of blunting of the response to upright
      tilting in heart failure being inversely related to the magnitude of increase in
      basal levels. CONCLUSIONS: Alterations in plasma levels of endothelin in
      congestive heart failure and in response to postural change were qualitatively
      and quantitatively similar to the alterations of known mediators of neurohumoral
      compensation. In addition, the increase in plasma endothelin-1 during upright
      tilting in normal subjects preceded the increases in circulating levels of the
      other vasoconstrictor mediators, consistent with a role of endothelin-1 in
      neurohumoral compensation for hemodynamic stress.

PMID- 1346511
TI  - Effect of xamoterol in Shy-Drager syndrome.
AB  - BACKGROUND: Xamoterol, a cardioselective beta 1-adrenoceptor partial agonist, has
      been reported to be effective on postural hypotension. We investigated the effect
      of xamoterol in five patients with Shy-Drager syndrome (SDS) in relation to their
      prevailing sympathetic nerve activity and sensitivity of beta-adrenoceptors and
      the change in circadian variation of blood pressure. METHODS AND RESULTS:
      Ambulatory blood pressure over 24 hours was monitored by noninvasive
      sphygmomanometer (model 5200, Spacelab). Plasma norepinephrine levels of SDS
      patients were significantly lower than that of normal subjects (n = 5) both at
      rest (54 +/- 15 versus 178 +/- 83 pg/ml) and after 10-minute standing (74 +/- 24
      versus 318 +/- 143 pg/ml). Infusion of isoproterenol (0.02 micrograms/kg/min)
      produced a mild rise of systolic blood pressure and tachycardia in normal
      subjects but resulted in marked hypotension and tachycardia in SDS subjects.
      After xamoterol administration (200 mg b.i.d.), systolic blood pressure and heart
      rate were significantly increased in the averages during the day; however,
      increases were more pronounced at night. In two of the five patients, the
      improvement in dizziness was large enough to enable them to increase their daily
      activities. CONCLUSIONS: Our observations suggest that 1) beta 1-selective, high
      intrinsic sympathomimetic activity of xamoterol increases blood pressure and
      heart rate in patients with SDS as a consequence of their prevailing beta 1
      adrenoceptor hypersensitive state, and 2) blood pressure monitoring over 24 hours
      appears to have important advantages in evaluating the therapeutic effects on
      postural hypotension.

PMID- 1346512
TI  - Study of CYP2D6 gene in children with autoimmune hepatitis and P450 IID6
      autoantibodies.
AB  - Cytochrome P450 IID6 is an autoantigen recognized by the sera of children
      affected with a subtype of autoimmune hepatitis. It was hypothesized that a
      mutation in the CYP2D6 gene could explain the autoimmune response in these
      patients. To examine this question, genomic DNA from peripheral lymphocytes (n =
      9) and liver (n = 1) of 10 patients with anti-LKM-1 antibody was analysed by
      Southern blot for genetic association studies between a particular CYP2D6
      haplotype and autoimmune hepatitis. In addition, a region of CYP2D6, from the
      same genomic DNA, was amplified by polymerase chain reaction (PCR) and digested
      by BstNI, in a search for the most prevalent 29B mutation, described in subjects
      who do not express the P450 IID6. Total RNA and proteins, prepared from the liver
      of an anti-LKM-1+ patient, were analysed by Northern and Western (immunoblot)
      blots respectively. Our results do not reveal any major structural change in the
      DNA of this patient at the CYP2D6 locus that could explain their autoimmune
      response. Corroborating this observation, no changes were noted either in P450
      IID6 mRNA size or in the corresponding protein. However, these data do not
      exclude the possibility of subtle changes in the protein due to point mutations
      in critical regions that might trigger an autoimmune response.

PMID- 1346513
TI  - Metered-dose inhalers versus hand-held nebulizers. Some answers and new
      questions.

PMID- 1346514
TI  - Substitution of metered-dose inhalers for hand-held nebulizers. Success and cost
      savings in a large, acute-care hospital.
AB  - Administration of beta-agonist bronchodilators by metered-dose inhaler (MDI) is
      as effective as administration by hand-held nebulizer (NEB). Recent studies have
      suggested that MDI therapy is less costly to administer and that routine
      substitution of MDI for NEB would result in considerable savings to patients and
      to hospitals. To our knowledge, the actual extent to which MDI therapy would
      replace NEB therapy or the cost savings realized has not been reported
      previously. We examined the success and impact on hospital costs of the routine
      substitution of MDI for NEB therapy in a large tertiary-care hospital. Following
      introduction of this strategy, more than 60 percent of all aerosol therapy was
      actually given as MDI. The mean amount of time spent by therapists to provide
      aerosol therapy was significantly reduced by MDI substitution, falling from 1,576
      +/- 131 h/mo, to 992 +/- 116 h/mo (p less than 0.002). The total cost to deliver
      aerosol therapy fell from $27,600 +/- $2,277/mo to $20,618 +/- $2,086/mo (p =
      0.008). Potential cost savings of $83,000 annually were achieved by the hospital,
      and charges to patients were lowered by approximately $300,000 per year. Routine
      substitution of MDI therapy for NEB therapy can be accomplished with
      considerable, but not total, success. This approach results in significant
      reductions in the cost of health care provision.

PMID- 1346515
TI  - Pathogenesis and treatment of portal-systemic encephalopathy: an update.

PMID- 1346516
TI  - Indomethacin accelerates clearance of labeled cells and increases DNA synthesis
      in gastrointestinal mucosa of the rat.
AB  - Sprague-Dawley rats treated with placebo, parenteral indomethacin, or oral
      prostaglandin E2 for six days were given an intraperitoneal injection of [3H]
      methyl-thymidine and killed at 45 min and 96 hr after labeling. Treatments were
      continued until death. The dpm/DNA index was determined in mucosal scrapings of
      the stomach, duodenum, and jejunum and used to estimate DNA synthesis (45 min)
      and the clearance of labeled cells (96 hr). Indomethacin increased the DNA
      synthesis in both the duodenal and jejunal mucosa (P less than 0.05). In
      comparison to the controls, the clearance of labeled cells from the antral,
      duodenal, and jejunal mucosa was accelerated by indomethacin treatment, whereas
      the elimination of labeled cells from the antral and jejunal mucosa was slowed by
      PGE2 treatment (P less than 0.05). DNA synthesis of the antral mucosa was
      significantly reduced by PGE2 (P less than 0.05). The cyclooxygenase blocker did
      not affect the cell kinetic parameters of the oxyntic mucosa. The plasma levels
      of somatostatin were significantly higher both in PGE2- and indomethacin-treated
      rats than in controls (P less than 0.05). It is concluded that indomethacin
      treatment increases the cell losses from the epithelial surface, which in turn
      trigger a compensatory trophic reaction. It is suggested that an important
      physiological action of endogenous prostaglandins is to regulate the outflow of
      cells from the superficial zones of the epithelium. Finally, this study disclosed
      the presence of hitherto unknown regulatory mechanisms that promote cell
      proliferation in the gastrointestinal mucosa despite inhibition of the synthesis
      of endogenous prostaglandins.

PMID- 1346517
TI  - Helicobacter pylori infection induces a decrease in immunoreactive-somatostatin
      concentrations of human stomach.
AB  - Immunoreactive-somatostatin (ir-somatostatin) concentrations of the gastric
      mucosa and gastric juice with Helicobacter pylori infection were measured in the
      human stomach. One hundred seventy-one patients (106 males, 65 females; mean age,
      52.0; range, 19-84 years) were registered. Gastric juice and mucosa were obtained
      with the usual endoscopy procedure. Somatostatin concentration was measured by
      radioimmunoassay. The ir-somatostatin concentrations in the H. pylori-negative
      group were significantly higher than in the positive group gastric mucosa,
      whereas its levels in gastric juice tended to decrease with H. pylori infection.
      There was an inverse correlation between luminal ammonia levels and ir
      somatostatin concentrations of the gastric mucosa. On the other hand, ir
      somatostatin concentrations of the gastric mucosa significantly decreased with
      chronic and active inflammatory change. This decrease was not correlated with the
      grade of active inflammation, which was in close relation to H. pylori infection,
      but with the grade of chronic inflammation. These results indicate that H. pylori
      may reduce ir-somatostatin concentrations of the human stomach and that its
      effect is partly mediated via luminal ammonia produced by H. pylori.

PMID- 1346518
TI  - Identification of carrot cDNA clones encoding a second putative proliferating
      cell-nuclear antigen, DNA polymerase delta auxiliary protein.
AB  - The proliferating cell-nuclear antigen (PCNA) plays a key role in the control of
      eukaryotic DNA replication. We have isolated two cross-hybridizing groups of cDNA
      encoding carrot homologs of PCNA. Sequence analysis and Southern-blot experiments
      showed that the cDNA were derived from two distinct genes. One corresponded to
      the typical PCNA, which is known to be highly conserved in eukaryotes from yeast
      to man; its mRNA is 1.2 kb in size and the calculated molecular mass of the
      protein is 29 kDa. The other encoded a larger PCNA homolog which has not
      previously been reported; the mRNA is 1.5 kb in size, the N-terminal three
      quarters (calculated molecular mass, 29 kDa) of the protein product is 88%
      identical at the amino acid level to the typical PCNA, but the protein has an
      extra C-terminal domain of 11 kDa. Both PCNA homologs were apparently coexpressed
      concomitant with somatic embryogenesis. The mRNA level of the novel homolog is 10
      20% that of the typical PCNA in the embryos. The presence of the second putative
      PCNA may provide new insight into studies on the mechanism of DNA replication in
      eukaryotes.

PMID- 1346519
TI  - An oxidized analog of alpha-human atrial natriuretic polypeptide is a selective
      agonist for the atrial-natriuretic-polypeptide clearance receptor which lacks a
      guanylate cyclase.
AB  - The differences in biological functions between alpha-human atrial natriuretic
      polypeptide (alpha-hANP) and its oxidized analog, MetSO-alpha-hANP, have been
      investigated. Analysis of the ANP receptor subtypes by affinity labeling has
      shown that a bovine pulmonary aortic endothelial cell line (CPAE cells) primarily
      expresses ANP-R1 (R, receptor) coupled to particulate guanylate cyclase, while
      Hela cells from human cervical carcinoma predominantly express ANP-R2, which
      lacks a guanylate cyclase. alpha-hANP could bind to both ANP receptor subtypes
      with high affinity, while MetSO-alpha-hANP showed more selective binding to ANP
      R2 than to ANP-R1. The activity of MetSO-alpha-hANP for stimulation of guanylate
      cyclase coupled to ANP-R1 was about 520-fold less than that of alpha-hANP (median
      effective dose = 2.5 nM for alpha-hANP, 1.3 microM for MetSO-alpha-hANP),
      indicating that MetSO-alpha-hANP was a partial agonist for this receptor. While
      this oxidized analog could inhibit the cAMP production through ANP-R2, with 0.15
      times the activity of alpha-hANP (median concentration = 0.31 nM for alpha-hANP,
      2.0 nM for MetSO-alpha-hANP). In in vivo studies, the diuretic activity of MetSO
      alpha-hANP was 25-100-fold less than that of alpha-hANP. In addition, MetSO-alpha
      hANP could potentiate the diuretic activity of alpha-hANP that was also caused by
      C-ANF4-23, a specific agonist for ANP-R2. These results demonstrate that MetSO
      alpha-hANP can act as an agonist more selective for ANP-R2 than for ANP-R1, both
      in vivo and in vitro. The relationship between receptor selectivities and the
      conformation of alpha-hANP or MetSO-alpha-hANP was also discussed.

PMID- 1346520
TI  - Diurnal rhythm of phosphorylation of rat liver acetyl-CoA carboxylase by the AMP
      activated protein kinase, demonstrated using freeze-clamping. Effects of high fat
      diets.
AB  - 1. Acetyl-CoA carboxylase was purified to homogeneity, in the presence of protein
      phosphatase inhibitors, from rat liver sampled without freeze-clamping. The
      enzyme was in a highly phosphorylated state (4.8 mol/subunit) of low specific
      activity, and could be dramatically reactivated by treatment with protein
      phosphatase-2A. Amino acid sequencing and fast-atom-bombardment mass spectrometry
      showed that the enzyme was phosphorylated in Ser79, Ser1200 and Ser1215, the
      three sites known to be phosphorylated in cell-free assays by the AMP-activated
      protein kinase. 2. The inactive enzyme could also be completely reactivated using
      a limited treatment with trypsin, which removes the N-terminal segment containing
      Ser79 and reduces the phosphate content to 3.5 mol/subunit. These results
      strengthen previous findings that it is phosphorylation at Ser79 by the AMP
      activated protein kinase that is responsible for the inactivation, and not the
      phosphorylation of the 220-kDa core fragment (which contains Ser1200 and
      Ser1215). 3. Analysis of the phosphorylation state of Ser79 in acetyl-CoA
      carboxylase from rat liver showed that phosphorylation occurs post mortem if
      freeze-clamping is not used. The higher phosphorylation observed in extracts made
      without freeze-clamping correlates with a large increase in AMP and decrease in
      ATP (presumably caused by hypoxia during removal of the liver), and with
      increased activity of the AMP-activated protein kinase. These results provide a
      rational explanation for the post mortem phosphorylation events, and re-emphasize
      the point that rapid cooling of cells and tissues is essential when measuring the
      expressed activity of acetyl-CoA carboxylase (as well as 3-hydroxy-3
      methylglutaryl-CoA reductase). 4. Using the freeze-clamping procedure, the ratio
      of 'expressed' activity (measured in the presence of protein phosphatase
      inhibitors) to 'total' activity (measured after complete dephosphorylation) of
      rat liver acetyl-CoA carboxylase showed a marked diurnal rhythm, changing from
      50% in the active form in the middle of the dark period to less than 10% active
      in the middle of the light period. The very low activity in the light period was
      associated with a high level of phosphorylation in Ser79. This diurnal rhythm is
      very similar to that previously described for the phosphorylation of 3-hydroxy-3
      methylglutaryl-CoA reductase, another substrate for the AMP-activated protein
      kinase. Neither the activity of the AMP-activated protein kinase nor the content
      of AMP, ADP or ATP changed between the dark or light periods.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1346521
TI  - Developmental changes in the activity of membrane-bound gamma-glutamyl
      transpeptidase and in the sialylation of synaptosomal membranes from the chick
      embryonic brain.
AB  - gamma-Glutamyl transpeptidase (GGT) is a membrane-bound sialoglycoprotein. The
      developmental changes in GGT activity and in sialic acid content were determined
      in a crude synaptosomal membrane fraction from the cerebral hemispheres of the
      chick embryo between days 11 and 19 of incubation. The GGT activity increased
      almost eightfold during the examined developmental period, while sialic acid
      content rose significantly only between days 11 and 15. Cortical administered on
      day 13 significantly increased GGT activity. On the other hand, the content of
      membrane bound sialic acid was not substantially affected. The value of the GGT
      apparent Michaelis constant (Kmapp) for gamma-glutamyl-p-nitroanilide in the
      presence of 20 mmol.l-1 glycylglycine was 1.5 mmol.l-1 and cortisol did not
      influence it. However, Vmax was increased by this hormone. The affinity of GGT to
      concanavalin A (ConA) did not change during development. Neither the
      administration of cortisol nor neuroaminidase treatment had any effect on the
      interaction of GGT with ConA. Desialylation of crude synaptosomal fraction did
      not change GGT activity. The results presented here suggest no developmental nor
      functional relationship between the activity of GGT and the level of sialylation
      in synaptosomal membranes from the cerebral hemispheres of the chick embryo.

PMID- 1346522
TI  - Effects of quinolinic acid on messenger RNAs encoding somatostatin and glutamic
      acid decarboxylases in the striatum of adult rats.
AB  - The level of expression of mRNAs encoding somatostatin and two isoforms of
      glutamic acid decarboxylase (Mr 65,000, GAD65 and 67,000, GAD67) was examined by
      quantitative in situ hybridization histochemistry in the striatum of adult rats
      after local injections of quinolinic acid. After a 2-week survival period, Nissl
      strains showed a profound loss of neurons in the injected striata. With a dose of
      120 nmol quinolinic acid, the lesioned area was completely devoid of somatostatin
      mRNA-positive neurons but contained cells expressing nicotinamide adenine
      dinucleotide-diaphorase activity (a marker of somatostatinergic interneurons in
      striatum). After 60 nmol of quinolinic acid, the number of neurons expressing
      somatostatin mRNA in the lesioned area was similar to controls but the level of
      labeling per neuron was increased. In the lesioned area, labeling for GAD65 mRNA
      was abolished and labeling for GAD67 mRNA markedly reduced. However, scattered
      neurons expressing GAD67 mRNA could still be detected. The majority of surviving
      GABA-ergic neurons expressed immunoreactivity to parvalbumin, a marker for
      striatal GABA-ergic interneurons. The results show that quinolinic acid induces
      dose-dependent alterations in the expression of striatal somatostatin mRNA and
      reveal a relative sparing of GABA-ergic interneurons in the quinolinic acid
      lesioned rat striatum.

PMID- 1346523
TI  - Prophylactic beta-blocker therapy: clinical implications of an aggregate
      analysis.

PMID- 1346524
TI  - Multi-level regulation of Thy-1 antigen expression in mouse T lymphomas.

PMID- 1346525
TI  - A new VH-CH recombinant in the rabbit.

PMID- 1346527
TI  - Proceedings of the Ninth Scientific Meeting of the Inter-American Society of
      Hypertension. Rio de Janeiro, Brazil, March 10-13, 1991.

PMID- 1346526
TI  - Molecular cloning and sequence analysis of bovine T-cell receptor gamma and delta
      chain genes.
AB  - Nine bovine T-cell receptor (Tcr) gamma chain (Tcrg) and three Tcr delta chain
      (Tcrd) cDNA clones were isolated from the cDNA libraries constructed from
      peripheral blood lymphocytes and thymocytes. Of nine Tcrg cDNA clones, only four
      were rearranged and contained specific V, J, and C gene segments, but the
      remaining five contained specific J and C or only C gene segments without the V
      gene segment. Three kinds of Tcrg-C, which were highly related at the nucleotide
      and amino acid levels, were found and designated as Tcrg-C1, Tcrg-C2, and Tcrg
      C3. Compared with human and mouse Tcrg-C, bovine Tcrg-C sequences are much
      longer, with about 27-55 amino acids corresponding to the hinge and connector
      regions, where the characteristic repetitive 5-amino acid motif (TTEPP or TTKPP)
      exists in sheep Tcrg-C as previously reported. From three Tcrd cDNA clones, two
      Tcrd-V and three Tcrd-J segments were isolated. The nucleotide and deduced amino
      acid sequences of bovine Tcrd-C, especially the transmembrane and cytoplasmic
      domains, are well conserved among species. As in bovine Tcrg-C, diversity of
      amino acid residues in the Tcrd-C region is concentrated in the hinge regions.
      Southern blot analysis showed that there are at least three Tcrg-C genes and one
      Tcrd-C gene in the bovine genome. The analysis also revealed the presence of Tcrg
      C- and Tcrd-C-associated restriction fragment length polymorphisms among bovine
      breeds.

PMID- 1346528
TI  - Differential actions of angiotensin II and angiotensin-(1-7) on transmitter
      release.
AB  - The central cardiovascular and dipsogenic effects of angiotensin II involve
      interactions with norepinephrine, dopamine, and serotonin. Our findings that
      angiotensin II receptors and substance P immunoreactivity show a parallel
      distribution in the dorsal medulla and that angiotensin II releases substance P
      from perfused rat medulla slices revealed the potential for a functional relation
      between these peptidergic systems as well. Additional evidence suggests that the
      heptapeptide angiotensin-(1-7) exerts its biological activities via selective
      angiotensin receptor subtypes. Thus, we compared the effects of these two
      peptides on release of substance P and monoamines in perfused slices of medulla
      and hypothalamus from 77 male Sprague-Dawley rats. Transmitter levels were
      determined in 6-minute collections of perfusate before (basal), during
      (experimental), and after (recovery) perfusion with either angiotensin-(1-7),
      angiotensin II, or Krebs' solution alone (control). Substance P was measured by
      radioimmunoassay and monoamines and their metabolites by high-performance liquid
      chromatography with electrochemical detection. In the medulla, 2 microM
      angiotensin II but not angiotensin-(1-7) significantly increased efflux of
      substance P (221 +/- 87% of basal) and norepinephrine (130 +/- 17% of basal)
      during the experimental period. The effect of angiotensin II on substance P was
      sustained into the recovery period. Dopamine and its metabolite 3,4
      dihydroxyphenylacetic acid were not detected in this brain region. In the
      hypothalamus, both angiotensin-(1-7) and angiotensin II increased substance P
      (169 +/- 30% and 141 +/- 35% of basal, respectively); the effect of angiotensin
      II was sustained throughout the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346529
TI  - Allelic loss on chromosome 22 correlates with histopathological predictors of
      recurrence of meningiomas.
AB  - Meningiomas are common tumors of the nervous system. Although usually benign,
      they may exhibit variable degrees of aggressiveness. Their probability of
      recurrence after subtotal resection has been correlated with several histological
      parameters. Independently, a loss of chromosome 22, as evidenced either by
      cytogenetics or by somatic loss of alleles, has been observed in about half of
      the cases studied. In 34 meningiomas we have examined the relationship between
      loss of chromosome 22 alleles and 6 histological predictors of recurrence.
      Significant correlations were found for 3 of these, i.e. prominent nucleoli (p
      less than 0.002), microscope count of mitoses (p less than 0.05) and nuclear
      pleomorphism (p less than 0.02). Correlation with the other 3, i.e. sheeting of
      cells, vascularity and micronecrosis, did not reach significance. Total tumor
      score, defined by the sum of the individual scores for these 6 parameters, was
      strongly correlated to allelic loss (p less than 0.0001). Thus, the loss of
      chromosome 22 alleles, which possibly contribute to the inactivation of tumor
      suppressor gene(s), might be a potent genetic marker of the aggressiveness of
      meningiomas.

PMID- 1346530
TI  - The alcohol dehydrogenase polymorphism in natural populations of Drosophila
      melanogaster: restriction map variation in the region of the Adh locus in
      populations from two hemispheres.
AB  - Restriction endonuclease variation in the 12 kb region surrounding the Adh locus
      was measured in seven Australian and six Chinese populations of Drosophila
      melanogaster. There is a higher level of nucleotide-substitution variation in the
      Australian populations than in the Chinese, which is possibly a reflection of
      their origins. None of the restriction site polymorphisms, nor any of the
      insertions, showed a significant association with latitude. A 0.2 kb deletion
      varied with latitude in the Chinese populations. In accordance with previous
      studies, a majority of the insertions were located in a region 1.5-3.5 kb 3' from
      the Adh coding region, and a majority of the deletions were at a site 3 kb 5' to
      the Adh coding region. Two of the insertions shared homologies with known mobile
      elements. Overall, the data suggest that restriction endonuclease variation in
      the Adh region is not related to the cline in Adhs frequencies.

PMID- 1346531
TI  - Population structure and mitochondrial DNA gene flow in Old World populations of
      Drosophila subobscura.
AB  - An extensive survey of mitochondrial DNA (mtDNA) restriction polymorphism in 156
      isofemale lines from 29 different geographic populations of Drosophila subobscura
      distributed throughout the Old World was carried out. Ten restriction enzymes
      were used, five of which revealed restriction site polymorphism. Of the 31
      restriction sites detected, 13 were found to be polymorphic. Comparisons with the
      mtDNA map of Drosophila yakuba indicate that the variable sites are mainly
      concentrated in protein genes, especially those corresponding to the NADH
      complex. A total of 13 different haplotypes were observed, two of which
      (haplotypes I and II) are quite frequent and widely distributed throughout the
      populations, whereas the other 11 with the exception of VIII, which deserves
      special attention, are each restricted to one population only and occur at low
      frequencies. The observed distribution of haplotypes, corroborated by a
      parsimonious unrooted tree, suggests an ancient origin of haplotypes I and II in
      the continent. In order to compare genetic structure according to mtDNA and
      allozymes, the 10 populations with higher population sizes were studied for 10
      polymorphic allozymes also. One striking result is the high degree of population
      structure of the mtDNA when compared to that obtained for allozymes. If an island
      model is assumed, estimates of gene flow give values of 0.013 and 1.89 migrants
      per generation for mtDNA and allozymes, respectively. What is apparent from these
      estimates is that Drosophila subobscura populations are effectively subdivided
      for mtDNA genes at migration rates at which nuclear genes (allozymes) are almost
      panmictic.

PMID- 1346532
TI  - Effect of BSO on the radiation response at low (0-4 Gy) doses.
AB  - Depletion of thiols by various agents has been shown to radiosensitize hypoxic
      cells. The agent BSO is used to specifically inhibit GSH synthesis, and the
      effect of this treatment on radiation response, particularly in the region of
      clinical interest, was studied using automated microscopic identification of
      cells for measurement of high survival levels. In both CHO and V79 cell lines,
      the enhancement rations were greater at low doses (80% S) than at high doses (2%
      S) in cells irradiated in hypoxia. GSH depletion also affected the aerobic
      response in both dose regions, with again higher ER's observed at low doses.
      These results support previous studies which suggest that GSH levels affect the
      shoulder portion of the survival curve. However, as with untreated cells, the
      OER's remain higher at high doses than at low doses, in BSO treated cells of both
      lines. These studies complement an earlier low-dose study on diamide by Skarsgard
      and co-workers, and were carried out to increase our understanding of the factors
      which affect radiation sensitivity in the range of doses used in fractionated
      regimens in the clinic.

PMID- 1346533
TI  - Taxol: a novel radiation sensitizer.
AB  - The investigational antineoplastic agent, taxol, a natural product from the yew,
      Taxus sp. L., is currently being evaluated in a series of Phase II clinical
      trials. To date, the drug has shown activity against ovarian cancer, lung cancer,
      and melanoma. Taxol is a potent microtubule stabilizing agent that selectively
      blocks cells in the G2 and M phases of the cell cycle and is cytotoxic in a time
      concentration dependent manner. It is well known from radiobiological principles
      that G2 and M are the most radiosensitive phases of the cell cycle. On the
      rationale that taxol could function as a cell-cycle selective radiosensitizer, we
      examined the consequences of combined drug-radiation exposures on the human grade
      3 astrocytoma cell line, G18. Survival curve analysis shows a dramatic
      interaction between taxol and ionizing radiation with the degree of enhanced cell
      killing dependent on taxol concentration and on the fraction of cells in the G2
      or M phases of the cell cycle. The sensitizer enhancement ratio (SER) for 10 nM
      taxol at 10% survival is approximately 1.8. These results obtained with cycling
      aerated radioresistant brain tumor cells indicate that significant advantage may
      derive from appropriate time-concentration dependent interactions in combined
      modality protocols.

PMID- 1346534
TI  - Characterization of the regulon controlled by the leucine-responsive regulatory
      protein in Escherichia coli.
AB  - The leucine-responsive regulatory protein (Lrp) has been shown to regulate,
      either positively or negatively, the transcription of several Escherichia coli
      genes in response to leucine. We have used two-dimensional gel electrophoresis to
      analyze the patterns of polypeptide expression in isogenic lrp+ and lrp mutant
      strains in the presence or absence of leucine. The absence of a functional Lrp
      protein alters the expression of at least 30 polypeptides. The expression of the
      majority of these polypeptides is not affected by the presence or absence of 10
      mM exogenous leucine. Outer membrane porins OmpC and OmpF, glutamine synthetase
      (GlnA), the small subunit of glutamate synthase (GltD), lysyl-tRNA synthetase
      form II (LysU), a high-affinity periplasmic binding protein specific for branched
      chain amino acids (LivJ), W protein, and the enzymes of the pathway converting
      threonine to glycine, namely, threonine dehydrogenase (Tdh) and 2-amino-3
      ketobutyrate coenzyme A ligase (Kbl), were identified as members of the Lrp
      regulon by electrophoretic analysis. We have shown that Lrp is a positive
      regulator of glutamate synthase and glutamine synthetase and that exogenous
      leucine has little or no effect on the expression of these proteins. In strains
      carrying a glnL deletion and in strains carrying the glnL2302 allele, which
      directs the synthesis of a GlnL protein that is constitutively active, expression
      of glutamine synthetase is no longer regulated by Lrp, demonstrating that the
      effect of Lrp on glutamine synthetase levels is indirect and requires an intact
      glnL gene. lrp::Tn10 strains grow poorly when arginine or ornithine is present as
      the sole nitrogen source in the medium. On the bases of present studies and
      previous research, we propose that Lrp is involved in the adaptation of E. coli
      cells to major shifts in environment, such as those which occur when E. coli
      leaves the intestinal tract of its animal host. Several genes required for amino
      acid and peptide transport and catabolism are negatively regulated by Lrp, and
      other genes required for amino acid biosynthesis and ammonia assimilation in a
      nitrogen-poor environment are positively regulated by Lrp.

PMID- 1346537
TI  - Peripheral blood stem cell autografts. Proceedings of the Second International
      Symposium. Mulhouse, September 29-October 2, 1991. Abstracts.

PMID- 1346536
TI  - Adhesion molecules on murine brain microvascular endothelial cells: expression
      and regulation of ICAM-1 and Lgp 55.
AB  - The mechanisms for the initiation of immune reactions in the central nervous
      system are poorly understood. In this report, we describe the presence of
      intercellular adhesion molecule-1 (ICAM-1) and Lgp 55 (suggested mouse homologue
      of human intercellular adhesion molecule-2, ICAM-2) on the surface of brain
      microvessel endothelium (EN) cells and show in vitro induction of ICAM-1
      molecules on EN cells with pro-inflammatory cytokines. ICAM-1 expression was
      detected using flow cytometry analysis with biotinylated anti-ICAM-1 antibody
      (YN1/1.7.4). Lgp 55 expression was characterized using PA3 monoclonal antibody.
      According to our results, 30-40% of the non-activated brain EN cells expressed
      ICAM-1 and 15-20% expressed Lgp 55 molecules. The ICAM-1 molecule expression was
      increased after the activation of the cells with recombinant murine gamma
      interferon (IFN-gamma), tumor necrosis factor (TNF-alpha), and interleukin-1
      alpha (IL1-alpha) in a dose-dependent manner. The increased ICAM-1 expression was
      detected as early as 2 h following the cytokine treatment and reached its maximum
      after 24 h. Transforming growth factor-beta (TGF-beta) did not influence the
      expression of ICAM-1 molecule. Lgp 55 molecule does not seem to be regulated by
      pro-inflammatory cytokines. ICAM-1 and Lgp 55 expression was found to be
      polarized on the luminal surface of EN by confocal laser microscopy suggesting
      accessibility for leukocytes. Inducible ICAM-1 expression may play a critical
      role in formation of inflammatory reactions inside the central nervous system.

PMID- 1346538
TI  - Diagnostic criteria for polyarteritis nodosa in childhood.
AB  - Clinical and laboratory features of 31 children with a diagnosis of polyarteritis
      nodosa were evaluated retrospectively. All the patients had musculoskeletal
      involvement, renal involvement, or both during the course of the disease. We have
      defined involvement of these two systems as the major diagnostic criteria in
      polyarteritis nodosa. Ten additional minor criteria were defined: (1) cutaneous
      findings, (2) gastrointestinal involvement, (3) peripheral neuropathy, (4)
      central nervous system involvement, (5) hypertension, (6) cardiac involvement,
      (7) lung involvement, (8) constitutional symptoms, (9) presence of acute-phase
      reactants, and (10) presence of hepatitis B surface antigen. We propose that the
      presence of five of these criteria, including at least one major criterion, is
      highly suggestive of polyarteritis nodosa; such a combination was present in 97%
      of our patients. Fourteen of the patients were treated with corticosteroids alone
      and 14 were treated with a combination of steroids plus cyclophosphamide or
      azathioprine. At the last follow-up examination six patients in the steroid group
      and nine in the combination group were considered to have complete remission of
      disease or inactive disease with persisting symptoms in an organ system. The
      overall mortality rate was 16%; renal involvement had the greatest adverse effect
      on outcome. We suggest that in patients with five of the 12 diagnostic criteria,
      especially those with renal involvement, therapy should be initiated promptly
      while diagnostic procedures are being carried out.

PMID- 1346540
TI  - Hepatitis C virus, a causative infectious agent of non-A, non-B hepatitis:
      prevalence and structure--summary of a conference on hepatitis C virus as a cause
      of hepatocellular carcinoma.

PMID- 1346539
TI  - Comparison of the postoperative intraocular pressure with Betagan, Betoptic,
      Timoptic, Iopidine, Diamox, Pilopine Gel, and Miostat.
AB  - A randomized, masked study measuring postoperative intraocular pressure at 4, 8,
      and 24 hours, two to seven days, and one month after planned extracapsular
      cataract extraction with posterior chamber lens implantation was conducted. Seven
      commonly used ocular hypotensive agents and a control, given at the completion of
      surgery, were compared: timolol maleate (Timoptic), levobunolol hydrochloride
      (Betagan), betaxolol hydrochloride (Betoptic), pilocarpine hydrochloride
      (Pilopine Gel), carbachol (Miostat), apraclonidine hydrochloride (Iopidine),
      acetazolamide (Diamox). There were significant differences between agents.
      Miostat was the most effective in controlling postoperative IOP, followed by
      Timoptic. Diamox, Pilopine Gel, and Betagan were equally effective. Betoptic was
      somewhat less effective and Iopidine was not significantly better than the
      control.

PMID- 1346542
TI  - Aorta-coronary bypass grafting for Takayasu's aortitis.

PMID- 1346541
TI  - Modulation and function of intercellular adhesion molecule-1 (CD54) on human
      retinal pigment epithelial cells.
AB  - As part of the blood-retina barrier, the neuroectodermally-derived retinal
      pigment epithelial (RPE) monolayer is strategically positioned to interact with
      circulating leukocytes and regulate their access to the retina. We, therefore,
      studied whether human RPE cells express intercellular adhesion molecule-1 (ICAM
      1), a specialized cell surface glycoprotein that binds the leukocyte function
      antigen-1 receptor present on all leukocytes. Using specific monoclonal antibody
      to ICAM-1, immunohistochemical staining of freshly-isolated primary and fourth
      passaged human RPE cells resulted in delicate reaction product that increased
      dramatically upon exposure to human recombinant (r) interferon-gamma (rIFN
      gamma), interleukin-1-beta (rIL-1 beta), or tumor necrosis factor-alpha (rTNF
      alpha). Fluorescence-activated cell sorting analysis demonstrated 2-fold
      increases in constitutive RPE ICAM-1 expression within 6 hours of exposure to
      physiologic concentrations of rIFN-gamma, rIL-1 beta, or rTNF-alpha. In
      standardized leukocyte adherence assays, cultured RPE cells showed avid binding
      of neutrophils that increased significantly after stimulation with rIFN-gamma,
      rIL-1 beta, or rTNF-alpha (p less than 0.001). In parallel assays, monoclonal
      antibody to either ICAM-1 on RPE cells, or subunits of leukocyte function antigen
      1 receptors on leukocytes significantly blocked leukocyte binding to unstimulated
      (p less than 0.001) or rIFN-gamma-stimulated RPE cells (p less than 0.001). To
      demonstrate RPE ICAM-1 expression in intact human tissue, fresh uveoretinal
      explants were exposed to rIFN-gamma, rIL-1 beta, or rTNF-alpha and stained using
      mAb to ICAM-1. Tissue sections of cytokine-stimulated explants revealed dramatic
      increases in RPE ICAM-1 immunoreactivity over the low levels observed in
      unstimulated uveoretinal tissue. Our results indicate that: (a) ICAM-1 is
      expressed at low levels on unstimulated RPE cells, (b) RPE ICAM-1 may be
      augmented by inflammatory cytokines, and (c) RPE ICAM-1 is a functional receptor
      mediating leukocyte binding. ICAM-1 on RPE cells at the blood-retina barrier may
      regulate leukocytic infiltration in ocular diseases in which leukocytes are
      important pathogenetically and may be important to the generation of ocular
      immune responses.

PMID- 1346543
TI  - Methylation status of the major breakpoint cluster region in Philadelphia
      chromosome negative leukemias.
AB  - It has been shown that a 600 bp long cluster of cell lineage specific
      hypomethylated sites in the major breakpoint cluster region (M-bcr) on chromosome
      22 exists in hematopoietic cells. To determine possible relationships between
      methylation patterns within the M-bcr and the stage of hematopoietic cell
      development, the M-bcr methylation status of 39 patients with leukemia and
      lymphoma and two patients with myelodysplastic syndrome with non-rearranged M
      bcrs was examined by BgIII-HpaII digestion. In the myeloid malignancies, the
      presence of a hypermethylated 4.8 kb BgIII-BgIII M-bcr allele was directly
      proportional to the combined myeloblast and promyelocyte percentage of the
      specimen, whereas the presence of a 2.5 kb BgIII-HpaII allele was directly
      proportional to the combined percentage of monocytic cells and neutrophils. All
      five acute monoblastic leukemias showed a methylation pattern that closely
      resembled neutrophils. All of thirteen surface immunoglobulin positive B-cell
      malignancies showed a distinct methylation pattern consisting of three or more
      BgIII-HpaII restriction fragments of 2.5 kb or less in length. The B-cell
      precursor leukemias showed heterogeneous M-bcr methylation patterns, with four of
      seven showing a B-cell pattern and three showing a hypermethylated pattern with
      4.8, 3.1/3.0 and/or 2.5 kb BgIII-HpaII M-bcr alleles. It is concluded that the M
      bcr methylation status is related to the maturation of the neutrophil series; the
      surface immunoglobulin positive B-cell malignancies are characterized by a
      distinct, extreme hypomethylation pattern of the M-bcr; and the B-cell precursor
      malignancies appear to have a heterogeneous M-bcr methylation pattern.

PMID- 1346544
TI  - Potentiation of opioid analgesia by cocaine: the role of spinal and supraspinal
      receptors.
AB  - These studies examined the effect of cocaine on the analgesia produced by
      systemically and centrally administered opioid agonists. Cocaine (50 mg/kg, s.c.)
      increased the analgesic potency of systemic, ICV and IT morphine; and the ICV and
      IT analgesic effects of the delta selective peptide, [D-Pen2,D-Pen5]enkephalin
      (DPDPE). Cocaine also increased the analgesic potency of the mu selective ligand
      [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) administered ICV. However, cocaine did
      not alter the ED50 for IT DAGO. GC-MS studies indicated that brain cocaine
      concentration was approximately 3.0 micrograms/g wet weight 45 min following s.c.
      administration. These results suggest that cocaine-induced increases in opioid
      analgesic potency are mediated at brain mu and delta receptors and spinal mu
      receptors. Furthermore, there might be functional differences between spinal and
      supraspinal sites at which DAGO produces analgesia.

PMID- 1346535
TI  - The stem cells of the liver--a selective review.
AB  - The current status of the much-debated question of the still-hypothetical stem
      cells of the liver is reviewed, with an emphasis on their role in
      hepatocarcinogenesis. The widely held view of the primacy of the hepatocyte,
      notably of the mononuclear diploid type, in this process--the "hepatocytic
      theory"--has been compared with variants of the "stem cell hypothesis" based on
      the "non-parenchymal epithelial cells" of the liver--the "oval" or biliary
      ductular cells, the "nondescript periductular" cells and the "primitive"
      bipotential epithelial cells. An attempt has been made to concentrate mainly on
      the more recent publications, in an effort to balance the conflicting opinions
      expressed by comparing results obtained by the newer procedures currently in use.
      Despite some interesting and relevant findings it appears that the evidence in
      favour of the stem-cell hypothesis is still circumstantial and that the
      hepatocytic theory has not been invalidated. Presumably the question of the
      hepatic stem cells will be answered when the riddle of hepatocarcinogenesis has
      been solved.

PMID- 1346545
TI  - Hypoglycemic effects of a beta-agonist, Ro 16-8714, in streptozotocin-diabetic
      rats: decreased hepatic glucose production and increased glucose utilization in
      oxidative muscles.
AB  - Streptozotocin (STZ)-induced diabetic rats are glycosuric, hyperglycemic,
      hyperketonemic, overproduce glucose, and have a decreased glucose utilization in
      oxidative muscles. Treatment with a beta-agonist, Ro 16-8714, decreases the
      glycosuria, hyperglycemia, hyperketonemia, and hepatic glucose production. Tissue
      glucose utilization was unchanged, except in oxidative muscles, where it was
      increased.

PMID- 1346546
TI  - Correlation of genetic and physical structure in the region surrounding the I2
      Fusarium oxysporum resistance locus in tomato.
AB  - The dominant gene I2 confers on tomato (Lycopersicon esculentum) resistance
      against the fungus Fusarium oxysporum f. sp. lycopersici race 2. A restriction
      fragment length polymorphism (RFLP) marker, TG105, has recently been found to be
      tightly linked to I2. The potential for cloning this gene by a reverse genetics
      approach prompted us to describe in both genetic and physical detail the region
      surrounding the I2 locus on chromosome 11. We have analyzed patterns of
      segregation of RFLP markers on chromosome 11 and Fusarium resistance in 140 F2
      plants from a cross between Fusarium-resistant and susceptible parental lines.
      Marker TG105 mapped 0.4 centiMorgan (CM) from I2. Physical analysis of TG105 and
      its flanking RFLP markers, TG26 and TG36, by pulsed field gradient gel
      electrophoresis (PFGE) yielded a restriction map for this region encompassing at
      least 620 kb of the tomato genome. TG105 and TG26 hybridized to the same 175 kb
      MluI-NruI restriction fragment. We have therefore linked two genetically distinct
      RFLP markers. Based on the 4.1 cM distance between them, we have assigned a mean
      value of 43 kb for each cM recombination distance in the vicinity of I2. This
      local ratio between physical and genetic distances is more than 10-fold below the
      average for the tomato genome. It should therefore be possible to clone I2 by
      chromosome walking from TG105.

PMID- 1346547
TI  - Tuberculous meningitis in patients infected with the human immunodeficiency
      virus.
AB  - BACKGROUND AND METHODS: Tuberculosis is a frequent complication of human
      immunodeficiency virus (HIV) infection. We describe the clinical manifestations
      and outcomes of tuberculous meningitis in patients with HIV infection, and
      compare them with those in non-HIV-infected patients. We reviewed the records
      from 1985 through 1990 at two large referral hospitals in Madrid for patients who
      had Mycobacterium tuberculosis isolated from cerebrospinal fluid. RESULTS: Of
      2205 patients with tuberculosis, 455 (21 percent) also had HIV infection, of whom
      45 had M. tuberculosis isolated from the cerebrospinal fluid. Of the 37 HIV
      infected patients with tuberculous meningitis for whom records were available, 24
      (65 percent) had clinical or radiologic evidence of extrameningeal tuberculosis
      at the time of admission. In 18 of 26 patients (69 percent), a CT scan of the
      head was abnormal. In most patients, analysis of cerebrospinal fluid showed
      pleocytosis (median white-cell count, 0.234 x 10(9) per liter) and
      hypoglycorrhachia (median glucose level, 1.3 mmol per liter), but in 43 percent
      (15 of 35), the level of protein in cerebrospinal fluid was normal. In four
      patients with HIV infection, tuberculosis was only discovered after their deaths.
      Of the 33 patients who received antituberculous treatment, 7 died (in-hospital
      mortality, 21 percent). Illness lasting more than 14 days before admission and a
      CD4+ cell count of less than 0.2 x 10(9) per liter (200 per cubic millimeter)
      were associated with a poor prognosis. Comparison with tuberculous meningitis in
      patients without HIV infection showed that the presentation, clinical
      manifestations, cerebrospinal fluid findings, and mortality were generally
      similar in the two groups. However, of the 1750 patients without HIV infection,
      only 2 percent (38 patients) had tuberculous meningitis, as compared with 10
      percent of the HIV-infected patients (P less than 0.001). CONCLUSIONS: HIV
      infected patients with tuberculosis are at increased risk for meningitis, but
      infection with HIV does not appear to change the clinical manifestations or the
      outcome of tuberculous meningitis.

PMID- 1346548
TI  - Glutamate receptors in the substantia nigra of Parkinson's disease brains.
AB  - Glutamic acid and its analogs are excitotoxins that might contribute to the
      pathogenesis of Parkinson's disease (PD). We measured four subtypes of glutamate
      binding sites autoradiographically in 20-microns sections from control and PD
      midbrains. N-Methyl-D-aspartate (NMDA) binding sites (eight control, eight PD)
      were very low in control (20 +/- 7 [SEM] fmol/mg protein) and were reduced in the
      PD pars compacta (2.6 +/- 1.1 fmol/mg protein; p less than 0.02). NMDA binding
      was also reduced in the red nucleus but not in periaqueductal gray (PAG). We
      measured alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA),
      metabotropic, and non-NMDA, nonkainate, non-quisqualate (NNKQ) sites in 10 PD and
      12 control midbrains. AMPA binding sites were reduced from 175 +/- 20 to 99 +/-
      16 (p less than 0.05) fmol/mg protein in PD pars compacta, NNKQ sites from 86 +/-
      10 to 50 +/- 12 (p less than 0.05) fmol/mg protein in total nigra, and
      metabotropic sites (15 +/- 5 fmol/mg protein) were unchanged. AMPA, metabotropic,
      and NNKQ binding were unchanged in red nucleus and PAG. The very low number of
      NMDA binding sites suggests that factors other than excitotoxicity mediated via
      NMDA receptors on nigral cell bodies play roles in the pathogenesis of PD. There
      may be a generalized loss of NMDA receptors in PD brains. AMPA and NNKQ binding
      sites appear to be located on dopamine neurons, although the role of NNKQ sites
      in normal nervous system function and human disease is unknown.

PMID- 1346550
TI  - Polymorphism in MS.

PMID- 1346549
TI  - Unsuspected, surreptitious drug-induced parkinsonism.

PMID- 1346551
TI  - Clinical and pathologic significance of the c-erbB-2 (HER-2/neu) oncogene.
AB  - Activation of the c-erbB-2 oncogene can occur by amplification of c-erbB-2 DNA
      and by overproduction of c-erbB-2 mRNA and c-erbB-2 protein. Approximately 20
      percent of breast carcinomas show evidence of c-erbB-2 activation, which
      correlates with a poor prognosis primarily in patients with metastasis to
      axillary lymph nodes. Studies that have attempted to correlate c-erbB-2
      activation with other prognostic factors in breast carcinoma have reported
      conflicting conclusions. The pathologic and clinical significance of c-erbB-2
      activation in other neoplasms is unclear and should be assessed by additional
      studies.

PMID- 1346552
TI  - Oncogenes and antioncogenes in human breast carcinoma.

PMID- 1346553
TI  - [Sudden death in heart failure. Analysis and prevention].
AB  - Sudden death is a frequent complication of heart failure occurring in 35 to 45
      per cent of the cases. This multifactorial event may be of haemodynamic origin
      (acute heart failure, electro-mechanical dissociation) or, more often, of
      rhythmic origin (torsade de pointe, sustained ventricular tachycardia,
      ventricular fibrillation, bradycardia, asystole). Numerous structural,
      haemodynamic, metabolic, ionic, neurohormonal and iatrogenic factors facilitate
      ventricular hyperexcitability. The main predictive factors of sudden death in
      heart failure are the presence of coronary heart disease and of reduced left
      ventricular ejection fraction; the prognostic value of ventricular rhythm
      disorders is controverted. Prevention of sudden death begins with correcting
      those factors which facilitate disturbances in rhythm and conduction. Beta
      blockers are effective in the post-infarction period, but there is no evidence
      that other drugs are useful. Identifying patients at high risk and determining
      the therapeutic approach that reduces this risk are still incompletely resolved
      problems.

PMID- 1346554
TI  - Nonconservative segregation of parental nucleosomes during simian virus 40
      chromosome replication in vitro.
AB  - Simian virus 40 chromosomes can be replicated in vitro with the same set of
      purified proteins required for the replication of naked DNA containing the viral
      origin. With these reconstituted systems, the fate of parental histones during
      replication was examined in vitro. The assembly of nucleosomes on replicating
      chromosomes was hardly affected by the presence of simultaneously replicating
      naked DNA competitor, suggesting that replication forks can traverse nucleosomes
      without the displacement of histones. Moreover, we demonstrate that the nascent
      nucleosomes were distributed almost equally between the leading and lagging
      strands. This distributive mode of nucleosome segregation favors the propagation
      of parental chromatin structures to both daughter cells, which can maintain
      cellular functions dictated by these structures during cell proliferation.

PMID- 1346556
TI  - Trophic doses of E2 prostaglandins do not influence the exocrine and endocrine
      pancreas in the presence of high levels of plasma somatostatin.
AB  - The aim of the present investigation was to study the effect of a long-term and a
      short-term treatment regimen with 15-R-15-methyl prostaglandin E2 and natural
      prostaglandin E2 (PGE2) on the endocrine cell populations of the rat pancreas.
      Graded oral doses of the analogue (5 and 50 micrograms/kg) and PGE2 (5000
      micrograms/kg) were given twice daily for 4 weeks. The pancreas was carefully
      excised and weighed. Sections from randomly taken pancreatic biopsy specimens
      were processed for immunohistochemistry or hematoxylin and eosin staining before
      quantitative estimations were made, using stereologic methods. The total
      pancreatic volumes of insulin-, glucagon-, polypeptide P-, somatostatin-, and
      chromogranin A-immunoreactive cells were not affected by E2 prostaglandins.
      Neither the total volume of the islets of Langerhans nor that of the pancreatic
      cell nuclei was affected. The size of pancreatic cell nuclei was the same in the
      groups. The plasma levels of the antitrophic peptide somatostatin were
      significantly increased in rats treated with doses of both the analogue and PGE2
      (p less than 0.05). In an additional short-term study rats were given oral
      placebo or 5000 micrograms/kg PGE2 twice daily for 5 days. The total endocrine
      pancreatic volume was not affected by PGE2. As in the long-term study, natural
      PGE2 did not affect the total pancreas volume or the total volume of pancreatic
      cell nuclei. These findings indicate that E2 prostaglandins produce no changes in
      the exocrine or endocrine pancreas in a dose range known to induce hyperplasia in
      the gastrointestinal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346555
TI  - Guanylin: an endogenous activator of intestinal guanylate cyclase.
AB  - Intestinal guanylate cyclase mediates the action of the heat-stable enterotoxin
      to cause a decrease in intestinal fluid absorption and to increase chloride
      secretion, ultimately causing diarrhea. An endogenous ligand that acts on this
      guanylate cyclase has not previously been found. To search for a potential
      endogenous ligand, we utilized T84 cells, a human colon carcinoma-derived cell
      line, in culture as a bioassay. This cell line selectively responds to the toxin
      in a very sensitive manner with an increase in intracellular cyclic GMP. In the
      present study, we describe the purification and structure of a peptide from rat
      jejunum that activates this enzyme. This peptide, which we have termed guanylin,
      is composed of 15 amino acids and has the following amino acid sequence,
      PNTCEICAYAACTGC, as determined by automated Edman degradation sequence analysis
      and electrospray mass spectrometry. Analysis of the amino acid sequence of this
      peptide reveals a high degree of homology with heat-stable enterotoxins. Solid
      phase synthesis of this peptide confirmed that it stimulates increases in T84
      cyclic GMP levels. Guanylin required oxidation for expression of bioactivity and
      subsequent reduction of the oxidized peptide eliminated the effect on cyclic GMP,
      indicating a requirement for cysteine disulfide bond formation. Synthetic
      guanylin also displaces heat-stable enterotoxin binding to cultured T84 cells.
      Based on these data, we propose that guanylin is an activator of intestinal
      guanylate cyclase and that it stimulates this enzyme through the same receptor
      binding region as the heat-stable enterotoxins.

PMID- 1346557
TI  - [Biochemical changes after salmeterol].

PMID- 1346558
TI  - Safety of pyridostigmine in hypertensive patients receiving beta blockers.
AB  - In the last decade, pyridostigmine, a quaternary carbamate that reversibly
      inhibits the enzyme acetylcholinesterase, was proposed for pretreatment of nerve
      gas (organophosphate) poisoning. The objective of this study was to assess the
      cardiovascular effects of pyridostigmine in patients treated with beta blockers.
      Eight hypertensive patients receiving regular treatment with beta blockers were
      randomized in a double-blind crossover study to receive pyridostigmine (30 mg 3
      times daily) or placebo for 2 days. Heart rate and blood pressure in the supine
      and standing positions were recorded every 2 hours during the day, and 24-hour
      Holter monitoring was performed. In addition, a symptom-limited exercise test was
      performed, and plasma catecholamine levels were determined at rest and at peak
      exercise. Pyridostigmine, as compared with placebo, did not induce any
      significant effect on heart rate, plasma catecholamine levels or resting blood
      pressure. Both systolic and diastolic blood pressures increased in accordance
      with exercise intensity (p less than 0.01), although a significantly lower
      diastolic blood pressure was observed when pyridostigmine was used (average
      decrease 5 mm Hg compared with placebo; p less than 0.01). No clinical adverse
      reactions were observed, confirming the relative safety of the combination of low
      dose pyridostigmine with beta-adrenergic blocking agents.

PMID- 1346559
TI  - The relation between nitrite inhalants, unprotected receptive anal intercourse,
      and the risk of human immunodeficiency virus infection.
AB  - The role of nitrite was evaluated between 1985 and 1988 in a study of sexual
      transmission of the human immunodeficiency virus (HIV) among homosexual male
      couples in Boston, Massachusetts. Initial enrollment data suggested that a
      history of unprotected receptive anal intercourse (odds ratio (OR) = 2.3, 95%
      confidence interval (CI) 1.4-3.6) and a history of nitrite use (OR = 1.7, 95% CI
      1.1-2.5) were independent risk factors for HIV infection. In addition,
      interaction between nitrite use and unprotected receptive anal intercourse was
      observed (OR = 5.5, 95% CI 2.8-11.1) after controlling for number of unprotected
      receptive anal sex partners and history of sexually transmitted diseases. Since
      it was felt that nitrite use might be a marker for unprotected receptive anal
      sexual activity, a supplemental questionnaire was administered to obtain
      information on simultaneous nitrite use and unprotected receptive anal
      intercourse. The supplemental data suggested a strong interaction between nitrite
      use and unprotected receptive anal intercourse in increasing the risk of HIV
      infection. In the adjusted analyses, the odds ratio for HIV infection was
      considerably greater among men who always used nitrites during unprotected
      receptive anal intercourse (OR = 31.8, 95% CI 12.9-76.7) compared with men who
      sometimes (OR = 7.1, 95% CI 2.1-23.6) or never (OR = 9.0, 95% CI 2.5-32.1) used
      them. These findings have preventive public health implications and may add
      insight into our understanding of the mechanism by which HIV infection spread
      rapidly among homosexual men in the early 1980s.

PMID- 1346560
TI  - Enhanced cerebral blood flow autoregulation in the newborn piglet by d
      tubocurarine and pancuronium but not by vecuronium.
AB  - Neuromuscular blockers may affect cerebral blood flow (CBF) regulation in the
      newborn. We studied the effects of d-tubocurarine (0.1 mg.kg-1, n = 8),
      pancuronium (0.1 and 0.4 mg.kg-1, n = 6 and 7), and vecuronium (0.1 and 0.4 mg.kg
      1, n = 6 and 7) on CBF measured over the same range of mean systemic blood
      pressure ([BP] 15-122 mmHg) in each group of newborn pigs; controls received
      normal saline (n = 7). The levels of BP during hypotension and hypertension were
      scaled at intervals of 5 +/- 1.6 mmHg and adjusted by inflating balloon-tipped
      catheters placed in the aorta. After saline, the low dose of pancuronium (0.1
      mg.kg-1), and the two doses of vecuronium, CBF was constant over the BP range of
      50-90 mmHg (r = -0.07-0.35, P greater than 0.20) but varied directly with BP
      beyond this range (tau = 0.38 - 0.60, P less than 0.05). In contrast, in pigs
      treated with d-tubocurarine and high-dose pancuronium, CBF remained constant from
      35 to 122 mmHg of BP (r = 0.14 - 0.37, P greater than 0.10) and changed minimally
      (4-12%) with BP greater than 105 mmHg compared to the other groups (41-59%, P
      less than 0.01). When BP was reduced below 30 mmHg, CBF also decreased less (20
      38%) in animals treated with d-tubocurarine and high dose-pancuronium than after
      the other treatments (58-67%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346561
TI  - New data on maintenance therapy with bronchodilators.

PMID- 1346563
TI  - Suppression of epicutaneous reactivity by terfenadine and loratadine.
AB  - We compared the relative antihistaminic effects of loratadine (10 mg),
      terfenadine (120 mg), and placebo in patients with tree pollen-induced allergic
      rhinitis. Wheals were produced by epicutaneous tests with serial dilutions of
      histamine phosphate, tree and grass pollen extracts before ingestion of
      medication. Repeat tests were performed after seven days of treatment.
      Terfenadine was more effective than both loratadine (P less than .01) and placebo
      (P less than .001) at suppressing histamine induced wheals. Terfenadine was more
      effective than placebo (P less than .01), but not loratadine at inhibiting both
      tree-induced and grass-induced epicutaneous reactions. In this study, terfenadine
      was more potent than loratadine in inhibiting both histamine-induced and allergen
      induced epicutaneous wheals.

PMID- 1346562
TI  - Effect of increasing dosage of an inhaled beta-2 specific agonist on pulmonary
      function, tremor, and cardiovascular indices.
AB  - In this investigation we evaluated the effect of increasing dosage, using an
      inhaled beta-2 specific agonist, pirbuterol, administered by a metered dose
      inhaler on pulmonary function, tremor, and cardiovascular parameters in nonacute
      adult asthmatic patients. This study was conducted with a randomized crossover
      study design in which each individual was administered a single dose of
      pirbuterol (0.4, 0.8 and 1.2 mg) [corrected] on separate days. Measurements of
      pulmonary function, tremor (by accelerometer readings), electrocardiogram, blood
      pressure and pulse were obtained at 0, 15, 30, 60, 90, 120, and 180 minutes
      following test drug administration where appropriate. These measurements were
      performed until there had been no change from baseline in tremor by 60 minutes or
      return of tremor measurements to within 15% of baseline for up to six hours. The
      data demonstrated that the onset of bronchodilator effectiveness had occurred by
      15 minutes after test drug administration (the first testing time). The peak
      percent change from baseline for the FEV1 occurred at 60 minutes after
      administration for all three test doses. The duration of activity was never truly
      established as there was no significant difference between any of the potential
      side effects for any of the three test drugs at any testing time period. This
      study demonstrated that with the beta-2 specific agent pirbuterol, administered
      as a metered dose inhaler, there is little risk of development of skeletal muscle
      or cardiovascular toxicity when as much as three times the recommended dose is
      used in a single usage, and that there is no direct correlation between the
      onset, peak, and/or duration of tremor with the onset and peak of bronchodilator
      efficacy with this agent.

PMID- 1346565
TI  - Surgeons gather to discuss AIDS, trauma, ethics, infection control, and quality
      assurance.

PMID- 1346564
TI  - Clonidine for patients with rapid atrial fibrillation.
AB  - OBJECTIVE: To determine whether clonidine can slow ventricular rate in patients
      with rapid atrial fibrillation. DESIGN: Randomized, controlled trial, with a 4
      hour follow-up period. SETTING: Emergency room of a university hospital.
      PATIENTS: A consecutive sample of 18 hemodynamically stable patients who were
      evaluated or treated for rapid atrial fibrillation. Exclusion criteria included
      acute or terminal illness; current use of antiarrhythmic agents, calcium-channel
      blockers, or beta-blockers; excessive hypertension; pulmonary, valvular, or
      pericardial disease; and electrolyte imbalance. INTERVENTIONS: Patients were
      randomly assigned to receive either "no treatment" (control group) or clonidine,
      0.075 mg orally, at baseline and after 2 hours if heart rate did not decrease by
      at least 20%. MEASUREMENTS: Blood pressure was measured by the same nurse in the
      same arm for 4 consecutive hours, and a full 12-lead electrocardiographic
      evaluation was done. MAIN RESULTS: Heart rate decreased to below 100 beats/min in
      eight of nine patients receiving clonidine compared with two of nine patients in
      the control group. The difference in the mean decreases in heart rate was 38
      beats/min (95% CI, 20 to 56 beats/min). Six patients who were treated with
      clonidine and one patient in the control group reverted to normal sinus rhythm.
      Systolic blood pressure decreased slightly in both groups, without significant
      differences. Clinical follow-up was uneventful. CONCLUSION: Low-dose clonidine
      was an easy, efficient, and effective treatment for patients with rapid atrial
      fibrillation who were hemodynamically stable.

PMID- 1346566
TI  - [Postoperative infection control in patients with hepatic, biliary tract, and
      pancreatic cancers].
AB  - Postoperative infection occurs more frequently in patients with malignant disease
      than in patients with benign disease. Postoperative infection control in patients
      with hepatic cancer, biliary tract cancer and pancreatic cancer is studied.
      Although in patients with jaundice due to malignancy the rate of positive
      bacterial culture of the bile collected at the time of PTCD was low, the rate of
      positive bile culture increased after 10 to 14 days of PTCD. The predominant
      strain was Enterococcus spp., followed by Klebsiella spp., Enterobacter spp. and
      E. coli in that order. These bacteria isolated from the bile were considered to
      be causative organisms of postoperative infection. Prophylactic antibiotics after
      the operation for jaundice due to malignancy should be chosen based on the
      results of bile culture. In patients undergoing hepatectomy, which is considered
      to be an aseptic operation, gram positive cocci such as S. aureus was the most
      frequently encountered organism. On the other hand, in patients undergoing
      hepatectomy and intestinal anastomosis, enteric bacteria were frequently isolated
      from the infectious foci. In this study there were 6 cases of methicillin
      resistant S. aureus (MRSA) postoperative infection, 3 cases after
      pancreatoduodenectomy, and 3 cases after hepatectomy. Even after an aseptic
      operation, postoperative MRSA infection is likely to occur in patients undergoing
      a more invasive operation, so hospital infection control should be again
      emphasized.

PMID- 1346567
TI  - Investigations into the mechanism by which sulfated polysaccharides inhibit HIV
      infection in vitro.
AB  - Sulfated polysaccharides have been shown to inhibit human immunodeficiency virus
      (HIV) infection in vitro. Dextrin sulfate, fucoidan, and dextran sulfate fail to
      neutralize virions directly, but interact with target cells to inhibit virus
      entry. Ionic interactions of sulfated polyanions with oppositely charged cell
      surface components, including CD4, have been assumed to be the inhibitory
      mechanism. It is shown that the sulfated polysaccharides inhibit infection of
      both CD4+ and CD4- cell lines by HIV and also that they inhibit HTLV-1 and, to a
      lesser extent, the simian retrovirus, MPMV, which use receptors other than CD4.
      One binding site for radiolabeled fucoidan on the surface of human T cells is an
      18 kD protein, but its significance is not yet clear.

PMID- 1346568
TI  - Dual tropism of HIV-1 IIIB for chimpanzee lymphocytes and monocytes.
AB  - In humans, macrophages serve as a major reservoir of human immunodeficiency virus
      (HIV-1) in the infected host and may play a role in the pathogenesis of the
      disease. In HIV-1-infected chimpanzees, however, virus could not be recovered
      from cells of the monocyte/macrophage lineage, leaving the question of macrophage
      tropism of HIV-1 in this species unresolved. The data reported that HIV-1 IIIB
      shows dual tropism and is infectious for both chimpanzee monocytes and
      lymphocytes in vitro. Viral replication in chimpanzee monocytes was clearly
      demonstrated by infection of allogeneic phytohemagglutinin (PHA) blasts in vitro
      and by electron microscopy (EM). EM revealed HIV particles associated with 10-15%
      of the HIV-1 IIIB-infected chimpanzee monocytes. Viral particles budding from the
      monocyte surface in the typical crescent form were noted as well. This is in
      contrast to the human situation, where monocytotropic HIV strains preferentially
      bud into and accumulate in cytoplasmic vacuoles. These results indicate that both
      lymphocytes and cells of the monocyte/macrophage lineage replicate virus in the
      chimpanzee; the cell tropism of viral strains, however, is different in
      chimpanzees and humans.

PMID- 1346569
TI  - rRNA sequence comparisons for assessing phylogenetic relationships among yeasts.

PMID- 1346570
TI  - Nature of the intermediate in the 3-oxo-delta 5-steroid isomerase reaction.
AB  - The role of Tyr-14 of 3-oxo-delta 5-steroid isomerase (KSI) was probed by
      analysis of the spectra of 3-amino-1,3,5(10)-estratrien-17 beta-ol (4) and
      equilenin (5) bound to the active site of KSI. The ultraviolet spectrum of 4
      bound to KSI is identical to that for 4 in neutral solution. This observation
      indicates that Tyr-14 does not protonate the amine group of 4 at the active site.
      By analogy, it is argued that the 3-oxo group of steroid substrates for KSI is
      not protonated during the reaction. In contrast, the fluorescence excitation
      spectra of 5 bound to KSI show characteristics of an ionized phenol, even at pH
      values as low as 3.8. It is concluded that the pKa of equilenin is perturbed from
      its value in solution of 9 to less than or equal to 3.5 at the active site of
      KSI. Similarly, the pKa of the intermediate dienol in the KSI reaction should be
      lowered to less than or equal to 4.5 when it is bound to KSI. Thus, the function
      of Tyr-14 as an electrophilic catalyst is likely the stabilization of the anion
      of the dienol by hydrogen bonding rather than by proton transfer.

PMID- 1346571
TI  - Role of Glu318 at the putative distal site in the catalytic function of
      cytochrome P450d.
AB  - Most microsomal P450s have a conserved "threonine cluster" composed of three Thrs
      (Thr319, Thr321, Thr322 for P450d) at a putative distal site. An ionic amino acid
      at 318 is also well conserved as Glu or Asp for most P450s. To understand the
      role of these conserved polar amino acids at the putative distal site in the
      catalytic function of microsomal P450, we studied how mutations at this site of
      P450d influence the activation of molecular oxygen in the reconstituted system.
      Catalytic activity (0.02 min-1) toward 7-ethoxycoumarin of the Glu318Ala mutant
      of P450d was just 6% of that (0.33 min-1) of the wild type, while those of
      Glu318Asp, Thr319Ala, and Thr322Ala were comparable to or even higher than that
      of the wild type. Consumption rates of O2 and formation rates of H2O2 of those
      mutants varied in accord with the catalytic activities. Especially, the
      efficiency (0.5%) of incorporated oxygen atom to the substrate versus produced
      H2O2 for the Glu318Ala mutant was much lower than that (3.7%) of the wild type,
      while that (58.8%) for the mutant Glu318Asp was 16-fold higher than that of the
      wild type. In addition, the autoxidation [Fe(II)---- Fe(III)] rate (0.074 s-1) of
      the Glu318Ala mutant was much lower than those (0.374-0.803 s-1) of the wild type
      and other mutants. Thus, we strongly suggest that Glu318 plays an important role
      in the catalytic function toward 7-ethoxycoumarin of microsomal P450d.

PMID- 1346572
TI  - Fe3+ binding to ovotransferrin in the presence of alpha-amino acids.
AB  - The ability of L-alpha-amino acids as synergistic anions for iron binding to
      ovotransferrin was investigated through electronic spectroscopy. Glycine and
      glutamic acid were found to form by far the most stable ternary Fe(3+)
      ovotransferrin-amino acid complexes. Less stable adducts were formed by amino
      acids with a hydroxy, amide or sulphur-containing group in the side chain, while
      the complexes with leucine, isoleucine, valine, lysine, arginine, tyrosine and
      tryptophan failed to form. Evidence is obtained that the synergistic
      effectiveness of the H2N-CH-COO- moiety is determined not only by the isoelectric
      point of the amino acid and the steric hindrance of its side chain, but a
      significant role is also played by interactions of the side chain itself with
      residues in the metal binding domains. Zn2+, Cd2+ and Co2+ are found to bind to
      ovotransferrin in the presence of glycine. 113Cd-NMR spectra on the Cd-derivative
      indicate that, according to the interlocking-sites model, the amino group of
      glycine directly binds to the metal ion.

PMID- 1346573
TI  - Altered glucose metabolism in adriamycin-induced heart failure.
AB  - Spontaneously hypertensive rats received 1 mg/kg of Adriamycin intravenously once
      a week for up to 12 weeks; their hearts were excised and perfused with buffer
      containing 5 mM [1-13C]glucose. Histological evidence of Adriamycin
      cardiotoxicity was evident after 8 and 12 weeks of treatment and was accompanied
      by a significant decrease in cardiac function. There were only minor changes in
      the 31P-NMR spectra in hearts following treatment; however, 13C-NMR spectra
      revealed decreased incorporation of label into the lactate, alanine and glutamate
      pools in hearts with severe tissue damage compared to hearts from untreated
      animals.

PMID- 1346574
TI  - Factor XIII-dependent generation of 5th complement component(C5)-derived monocyte
      chemotactic factor coinciding with plasma clotting.
AB  - Blood coagulation or plasma clotting caused generation of a monocyte chemotactic
      factor(s) in vitro. The chemotactic factor, of which the apparent molecular mass
      was 75 kDa, shared antigenicity with complement C5 and possessed the affinity to
      monocytes, but not to polymorphonuclear leukocytes. The generation of the
      chemotactic factor was hindered in the presence of a thiol enzyme inhibitor, p
      chloromercuriphenyl sulfonic acid, at the concentration of 1 mmol/l, although the
      gelation of plasma was apparently completed. Furthermore, the generation of
      chemotactic factor was not observed when a plasma deficient in blood coagulation
      factor XIII, which is a precursor of a thiol enzyme, plasma transglutaminase, was
      used; and the activity normally appeared when the deficient plasma was
      reconstituted with purified factor XIII or with a tissue transglutaminase prior
      to clotting. When the human sera were injected into guinea pig skin, the serum
      derived from normal plasma or from the reconstituted factor XIII deficient one
      caused mononuclear cell infiltration, however, the serum from the deficient
      plasma without reconstitution infiltrated to a significantly smaller extent.
      These results indicated that the complement system was initiated somehow during
      the clotting process resulting in the generation of the C5-derived monocyte
      chemotactic factor in cooperation with factor XIIIa (activated factor XIII).

PMID- 1346575
TI  - 2-Chlorodeoxyadenosine treatment of lymphoid malignancies.

PMID- 1346576
TI  - Characterization of the myeloid-specific CD11b promoter.
AB  - The CD11b/CD18 heterodimeric surface antigen is expressed exclusively on human
      monocytes, macrophages, granulocytes, and natural killer cells. During
      differentiation of myeloid cell lines, CD11b steady state messenger RNA levels
      increase significantly; we show here that CD11b transcription rates increase
      commensurately. A 1.7-kb fragment of CD11b 5' flanking sequence directs
      expression of a reporter gene specifically in myeloid cell lines. Deletion
      analysis localizes elements directing high levels of tissue-specific reporter
      gene expression to the 412 bp proximal to the transcriptional start site. This
      sequence contains two consensus binding sites for Sp1, a GATA motif, and a purine
      rich sequence that presents potential binding sites for members of the ets family
      of genes. Analysis of this promoter should result in the isolation of myeloid
      specific transcription factors and the development of methods to direct the
      myeloid-specific expression of heterologous genes.

PMID- 1346577
TI  - Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA).
AB  - We administered one course of 2-chlorodeoxyadenosine (2CdA) at 4 mg/m2 daily for
      7 days by continuous intravenous infusion to 46 patients with hairy cell
      leukemia. Complete remissions occurred in 36 patients (78%; 95% confidence
      limits, 63% to 89%), partial remissions in five (11%), and a minor response in
      one. One patient died of candida sepsis 3 weeks after beginning treatment and
      three patients were clearly resistant to therapy. These three either had
      morphologically atypical hairy cells, less than 20% of which expressed Ig light
      chain on the cell surface, or had failed prior treatment with deoxycoformycin and
      interferon-alpha. At a median of 37 weeks since discontinuation of therapy,
      recurrent thrombocytopenia has developed in one patient, whose marrow remains
      normal, while a bone marrow relapse has occurred in another patient, whose blood
      counts remain normal. Treatment produced a greater than 50% decrease in
      neutrophil count in 26 patients, which lasted 3 to 4 weeks and was associated
      with an increased incidence of febrile episodes. These episodes occurred in 21
      patients but were associated with documented infection in only four patients.
      Decreases in the number of CD4+ lymphocytes appeared to occur regularly after
      treatment and have persisted for a median of 18 weeks without obvious clinical
      significance. Although years of follow-up will be needed, our results confirm
      Piro et al's observation (N Engl J Med 322: 1117, 1990) that 2CdA appears to be
      highly effective in the treatment of hairy cell leukemia.

PMID- 1346578
TI  - Rapid recovery from cytopenia in hairy cell leukemia after treatment with 2
      chloro-2'-deoxyadenosine (CdA): relation to opportunistic infections.
AB  - Sixteen patients with symptomatic hairy cell leukemia were treated with a single
      course of 2-chloro-2'-deoxyadenosine (CdA), 0.7 mg/kg total dose. Twelve patients
      achieved complete remission (CR). One patient with a CD19+/CD5+/CD25- phenotype
      and one with a pentostatin-treated CD19+/CD25- variant form had minor responses.
      Two patients with advanced disease and poor performance status died early from
      invasive mycosis. Three patients recovered from infections caused by
      cytomegalovirus and by candida. No patient had infections caused by bacteria or
      by unknown organisms. The median time to full recovery from anemia and
      thrombocytopenia was 6 and 2 weeks from start of therapy, respectively. Patients
      with infections, however, recovered at 13 and 5 weeks, respectively. Neutrophil,
      monocyte, and lymphocyte counts returned to normal at a median of 5, 5, and 10
      weeks, respectively. Infections developed more frequently in pancytopenic
      patients than in those with one or more blood cell count within the normal range
      (P less than .01). All patients with one or no previous therapy had a CR, whereas
      those with more than one previous regimen had a lower CR rate (P less than .01).
      Thus, 1 week of CdA therapy frequently induced CR also in patients resistant to
      interferon. Toxicity was limited, and recovery from cytopenia was faster than
      what is reported during interferon therapy.

PMID- 1346579
TI  - Bronchodilator treatment in asthma: continuous or on demand?

PMID- 1346580
TI  - A general theory for host seeking decisions in mosquitoes.
AB  - We develop a theory for host seeking decisions in mosquitoes that explicitly
      considers the tradeoffs mosquitoes face in allocation to somatic and gametic
      function. Specifically, we consider conditions under which mosquitoes should seek
      out nectar and blood hosts upon encountering host odours. Results from
      development of a dynamic model that considers free and crop energy states suggest
      that mosquitoes should seek out blood hosts under a wide variety of conditions
      but that decisions to seek nectar depends upon crop volume, concentration and
      free energy. This pattern arises because mosquitoes carrying large crop loads are
      constrained in their ability to obtain large blood meals due to space limitations
      in the abdomen. The predicted patterns of behaviour are supported by published
      observations of mosquito behaviour.

PMID- 1346581
TI  - Sulphasalazine induced autoimmune syndrome.

PMID- 1346582
TI  - 'Natural history' of hepatectomy.
AB  - The aim of this study was to describe biochemical and liver function test changes
      after hepatectomy in 33 patients with the following characteristics: absence of
      underlying liver disease, no blood or plasma transfusion during the perioperative
      period, uneventful postoperative course. Resection with a temporary pedicle
      inflow occlusion (10-45 min) consisted of unisegmentectomy or less in 15 patients
      and bisegmentectomy or more in 18. Blood tests showed: a correlation between
      aminotransferase rise and duration of ischaemia, and a fall in prothrombin time
      and factor V levels correlating with the weight of resected specimen at day 1; a
      moderate gamma-glutamyl transpeptidase and alkaline phosphatase elevation and a
      rise in fibrinogen level correlating with the extent of resection at day 7.
      Changes in haemoglobin level, white cell count, platelet count, prothrombin time,
      factor V level and serum bilirubin level tended to return to preoperative levels
      by day 7. For gamma-glutamyl transpeptidase and alkaline phosphatase, increased
      levels persisted for 8-12 weeks after resection. These results, in this selected
      group of patients, allow a description of the 'natural history' of hepatectomy.
      The knowledge of these 'natural' changes may contribute to the early detection of
      postoperative complications.

PMID- 1346583
TI  - Interferon-induced increase in sensitivity of ovarian cancer targets to lysis by
      lymphokine-activated killer cells: selective effects on HER2/neu-overexpressing
      cells.
AB  - Overexpression of the HER2/neu oncogene in ovarian tumor cells is associated with
      relative resistance to lymphokine-activated killer (LAK) cell cytotoxicity.
      Treatment with gamma-interferon (IFN-gamma) (200-2000 units/ml) for 3 days
      markedly enhanced the sensitivity of HER2/neu-overexpressing ovarian tumor cells
      to LAK cells but had no effect on the sensitivity of nonexpressing ovarian
      targets. Increased sensitivity to lysis was associated with an increase in
      effector-target conjugate formation, the induction of target cell intercellular
      adhesion molecule 1 (ICAM-1) expression, and the down-regulation of HER2/neu
      expression. Anti-ICAM-1 antibody blocked the enhanced lysis, indicating that ICAM
      1 is important in the increased sensitivity to LAK cells. However, induction of
      ICAM-1 expression did not correlate well with enhanced sensitivity to lysis; it
      was maximal after 24 h of exposure to IFN-gamma and still present 24 h after
      removing IFN-gamma. In contrast, enhanced lysis required 3 days of exposure to
      IFN-gamma and was reversed within 24 h after removal of IFN-gamma. These data
      indicate that, although ICAM-1 is necessary, it is not sufficient for the IFN
      gamma-induced enhancement of sensitivity to LAK lysis.

PMID- 1346584
TI  - Consistent association of 1p loss of heterozygosity with pheochromocytomas from
      patients with multiple endocrine neoplasia type 2 syndromes.
AB  - Pheochromocytomas and medullary thyroid cancers (MTCs) are neuroendocrine tumors
      which arise sporadically or as part of the multiple endocrine neoplasia type 2
      (MEN-2) hereditary syndromes. The most consistent molecular genetic abnormality
      which has been described in these tumors is loss of heterozygosity (LOH) of the
      short arm of chromosome 1 (1p). This finding is particularly interesting because
      the predisposition gene for the hereditary form of these tumors has been mapped
      to chromosome 10, but LOH on chromosome 10 in MEN-2 tumors is found rarely. We
      have used a battery of 1p DNA probes to elucidate the region of loss of 1p in 18
      pheochromocytomas and 27 MTCs. Using restriction fragment length polymorphism
      analysis, we identified loss of all or a portion of 1p in 12 of 18
      pheochromocytomas. 1p LOH was identified in nine of nine pheochromocytomas in MEN
      2A and -2B patients, compared with only two of seven sporadic pheochromocytomas.
      We also found 1p LOH in one of two von Hippel-Lindau patients. LOH on 1p was
      noted in only three of 24 informative MTCs, and these were from patients with MEN
      2A. In most of the pheochromocytomas, the entire short arm of chromosome 1p
      appears to have been lost; however, in three of the non-MEN pheochromocytomas and
      in three MEN-2A MTCs, the region of loss is smaller, allowing estimation of the
      smallest region of overlap. The combined data for MTCs and pheochromocytomas
      suggest that the smallest region of overlap of LOH is bounded by D1S15 (1pter
      p22) and D1Z2 (1P36.3), excluding a region around MYCL (1p32). Although other
      regions of 1p should not be completely ruled out, the data suggest that this
      region may harbor a tumor suppressor gene or genes whose inactivation is
      important in the development of these tumors. Furthermore, the strong association
      between 1p LOH and the MEN-2 syndromes, especially in pheochromocytomas, suggests
      a relationship between the predisposition gene on chromosome 10 and the loss of
      the suppressor gene on 1p. Alternatively, other loci may be more important in
      sporadic disease.

PMID- 1346585
TI  - Molecular heterogeneity of somatostatin analogue BIM-23014C receptors in human
      breast carcinoma cells using the chemical cross-linking assay.
AB  - Distinct proteins complexed with somatostatin and the somatostatin analogue BIM
      23014C were revealed in human breast cancer cells using the cross-linking assay.
      One BIM-23014C-specific complex (Mr 57,000) was observed in MCF-7 (monolayer,
      nodule, and tumor) and T47D. Growth inhibition of MCF-7 tumor xenografts by BIM
      23014C was dose related in the 6-day subrenal capsule assay. Three complexes (Mr
      27,000, 42,000, and 57,000) were detected in MDA-MB-231, and no complex was
      visible in HBL-100. No correlation was found between receptors for BIM-23014C and
      epidermal growth factor in these lines. Twenty-seven of 30 human breast tumors
      (90%) had at least one BIM-23014C receptor. Sixteen had three complexes (Mr
      27,000, 42,000, and 57,000). Six had the two complexes (Mr 27,000 and 57,000),
      two had Mr 42,000 and 57,000 complexes, two had just the Mr 27,000 complex, and
      one had just the Mr 42,000 complex. The presence of the three BIM-23014C
      receptors was positively correlated (P less than 0.05) to the low amount of sex
      steroid receptors (less than 20 fmol/mg) [seven of eight (estrogen receptor
      negative, progesterone receptor negative) versus four of 14 (estrogen receptor
      positive, progesterone receptor positive)]. Another positive correlation was
      established between the absence of progesterone receptors and the presence of
      these three complexes [12 of 16 (progesterone receptor negative) versus four of
      14 (progesterone receptor positive)]. This high percentage of BIM-23014C receptor
      positive biopsies and its inhibitory activity would support its clinical
      potential for the treatment of breast cancer.

PMID- 1346586
TI  - Deletion mapping on the short arm of chromosome 3 in squamous cell carcinoma and
      adenocarcinoma of the lung.
AB  - We examined loss of heterozygosity in 49 adenocarcinomas and 18 squamous cell
      carcinomas of the lung with 19 RFLP markers on the short arm of chromosome 3.
      Although no interstitial deletions were observed in any squamous cell carcinomas,
      interstitial or partial deletions were detected in 23 adenocarcinomas.
      Identification of two common regions of deletion in adenocarcinomas, at 3p21.3
      and 3p14.1-21.1, suggested the presence of at least two tumor suppressor genes on
      3p within the same regions commonly deleted in renal cell carcinomas. Correlation
      between the frequency of loss of heterozygosity on 3p and histopathological grade
      of adenocarcinoma also was observed. These results imply an etiological
      difference between two major types of non-small cell lung cancers, adenocarcinoma
      and squamous cell carcinoma.

PMID- 1346587
TI  - Glutaminase and glutamine synthetase activities in human cirrhotic liver and
      hepatocellular carcinoma.
AB  - Glutamine synthetase and glutaminase activities in human cirrhotic liver tissues
      and hepatocellular carcinomas were determined for comparison with normal liver
      tissues. In hepatocellular carcinoma, glutamine synthetase activity was
      approximately one-third of that in normal liver, whereas no detectable change in
      the enzyme activity was observed in cirrhotic liver. Phosphate-dependent and
      phosphate-independent glutaminase activities were increased approximately 20-fold
      and 6-fold, respectively, both in the carcinoma and cirrhotic liver compared with
      those from normal liver, Oxypolarographic tests showed that the rate of glutamine
      oxidation in the tumor and cirrhotic liver mitochondria was about 5-fold higher
      than that in the liver mitochondria. The rate of glutamate oxidation in the liver
      mitochondria was comparable to that in the cirrhotic liver and tumor
      mitochondria. Glutamine oxidation was inhibited by prior incubation of the
      mitochondria with 6-diazo-5-oxo-L-norleucine, which inhibited mitochondrial
      glutaminase. These results indicate that the product of glutamine hydrolysis,
      glutamate, is catabolized in the tumor and cirrhotic liver mitochondria to supply
      ATP. In the liver and cirrhotic liver mitochondria, glutamate was oxidized via
      the routes of transamination and deamination. On the other hand, glutamate
      oxidation was initiated preferentially via a transamination pathway in the tumor
      mitochondria.

PMID- 1346589
TI  - Chromosome alterations in human small cell lung cancer: frequent involvement of
      5q.
AB  - Deletions of the 3p chromosome region and molecular alterations of the tumor
      suppressor genes RB1 and TP53, located, respectively, at 13q14 and 17p13, are
      well-documented in small cell lung cancer (SCLC). Because of technical
      difficulties, karyotypes of primary SCLC specimens are rarely reported. In this
      study, detailed cytogenetic analysis was performed on 13 early passage SCLC cell
      lines and fresh specimens, including 4 lung primaries. Numerous chromosome
      alterations were found, even in newly diagnosed primary tumors. Consistent with
      previous molecular studies, chromosomal losses of 3p (13 cases) and 17p13 (12
      cases) were frequently observed. Numerical losses of chromosome 13 and structural
      rearrangements affecting 13q14 were identified in 10 specimens. In addition,
      losses of chromosome 5 and structural alterations of 5q occurred in 12 tumors;
      among these, 9 displayed losses of region 5q13-q21. Double minutes were found in
      4 cases (3 of 5 specimens from patients who received prior cytotoxic therapy but
      only 1 of 8 from untreated patients). DNA analysis revealed amplification of
      either MYC1 or MYCN in cells from each of these 4 tumors. Overall, the
      cytogenetic findings underscore that progression of SCLC involves multiple
      genetic changes and suggest further that a tumor suppressor gene(s) on 5q may
      contribute to SCLC tumorigenesis.

PMID- 1346588
TI  - Effect of tumor size on the enhancement by gamma interferon of the localization
      of radiolabeled F(ab')2 fragments of anti-intercellular adhesion molecule-1
      monoclonal antibodies in human colon carcinoma cells grafted in nude mice.
AB  - Because tumor size has been shown to influence the specific accumulation of
      radiolabeled anti-tumor-associated antigen monoclonal antibodies (mAb), the
      present study has investigated the effect of the tumor size on the enhancement by
      gamma interferon (IFN-gamma) of the accumulation of radiolabeled mAb in malignant
      lesions. Intercellular adhesion molecule-1 (ICAM-1) has been used as a marker
      because of its high susceptibility to modulation by IFN-gamma. F(ab')2 fragments
      of anti-ICAM-1 mAb CL207.14 have been selected to visualize malignant lesions,
      because they had been shown to be more sensitive probes for our experiments than
      whole IgG. Administration of IFN-gamma to human colon carcinoma-bearing nude mice
      increased the expression of ICAM-1 in the xenografts and the specific
      accumulation of 125I-F(ab')2 fragments of anti-ICAM-1 mAb CL207.14. The latter
      effect is influenced by the size of the lesions, because it was observed only in
      tumors with an approximate diameter of 8 mm and an approximate weight of 250 mg.
      If these results obtained in an animal model system are applicable to patients
      with malignant diseases, the present investigation suggests that administration
      of IFN-gamma enhances the sensitivity of immunoscintigraphy and the efficacy of
      immunotherapy with radiolabeled mAb which recognize tumor-associated antigens
      that are susceptible to modulation by IFN-gamma. However, the effect of IFN-gamma
      is not a general phenomenon but is influenced by the size of the malignant
      lesions.

PMID- 1346590
TI  - Neuroleptic treatment of schizophrenia.

PMID- 1346591
TI  - Prolonged paralysis after long-term vecuronium infusion.

PMID- 1346592
TI  - Chromosome 21 genetic linkage data set based on the Venezuelan reference
      pedigree.

PMID- 1346593
TI  - Inhibitory effect of circulating insulin on glucagon secretion during
      hypoglycemia in type I diabetic patients.
AB  - OBJECTIVE: To clarify whether the circulating insulin level influences hormonal
      responses, glucagon secretion in particular, during hypoglycemia in patients with
      insulin-dependent (type I) diabetes. RESEARCH DESIGN AND METHODS: Nine type I
      diabetic patients were studied. During two separate experiments, hypoglycemia was
      induced by low-dose (244 pmol.kg-1.h-1) and high-dose (1034 pmol.kg-1.h-1)
      intravenous insulin infusions for 180 min in each case. The arterial blood
      glucose level was directly monitored every 1.5 min, and glucose was infused in
      the high-dose test to clamp the arterial blood glucose level to be identical as
      in the low-dose test. RESULTS: Despite the fact that the plasma insulin level was
      four times higher in the high-dose than in the low-dose test (740 +/- 50 vs. 180
      +/- 14 pM), a close to identical arterial hypoglycemia of approximately 3.3 mM
      was obtained in the two experiments. During hypoglycemia, a significant rise of
      the plasma glucagon level was found only in the low-dose test (188 +/- 29 vs. 237
      +/- 37 ng/L, P less than 0.05), and the incremental area under the glucagon curve
      was significantly greater in the low-dose than in the high-dose test (140 +/- 19
      vs. -22.7 +/- 34 ng/L.h-1, P less than 0.005). The responses of plasma
      epinephrine, norepinephrine, growth hormone, pancreatic polypeptide, and
      somatostatin were similar in both tests and, consequently, were not significantly
      modified by the circulating insulin level. CONCLUSIONS: This study demonstrates
      that, in type I diabetic patients, the glucagon response to hypoglycemia is
      suppressed by a high level of circulating insulin within the physiological range.
      Our findings may help to explain the impairment of glucagon secretion during
      hypoglycemia frequently seen in these patients.

PMID- 1346594
TI  - Somatostatin receptors in human colorectal cancer.
AB  - We have previously reported that somatostatin may reduce tumour cellular
      proliferation in patients with colorectal carcinoma. However, it is not known
      what proportion of primary colorectal cancers express somatostatin receptors. We
      have therefore evaluated somatostatin receptor status in 50 primary colorectal
      cancers. Twelve (24%) of the cancers were shown to be somatostatin receptor
      positive. There was no correlation between receptor status and tumour stage or
      grade.

PMID- 1346595
TI  - Detection of human papillomavirus types 16 and 18 in the exfoliated cervical
      cells using the polymerase chain reaction.
AB  - We applied the polymerase chain reaction (PCR) to detect HPV 16 and 18 in
      cytological samples obtained from the uterine cervices of Japanese women. HPV
      infection was detected in 17 (25%) of 67 with CIN and 11 (37%) of 30 with
      cervical carcinoma. It is notable that 11 (16%) of 69 women with normal cervices
      were infected with either HPV 16 or 18. The polymerase chain reaction is
      sensitive and useful for epidemiological studies.

PMID- 1346597
TI  - Macrophage- and lymphocyte-subtypes in the endometrium during different phases of
      the ovarian cycle.
AB  - The presence of immunocompetetive cells in the endometrium during the
      proliferative and secretory phase of the ovarian cycle is demonstrated on the
      light and electron microscopic level using monoclonal antibodies (MoAb). Subtypes
      of monocytes, macrophages and T-lymphocytes appear during the different phases in
      variable extent and different localization. Some subpopulations of the
      monocyte/macrophage system and T-helper lymphocytes increase in number on day
      21/22. Our observations indicate that cells with bone marrow origin take part in
      functional events of the endometrium during the ovarian cycle.

PMID- 1346596
TI  - Hormonal and ultrasound characteristics of menstrual function during chronic
      hemodialysis and after successful renal transplantation.
AB  - The cycles of 11 renal transplant recipients (RTR), at least 24 months after
      stabilization of graft function and four hemodialyzed (HD) patients, menstruating
      regularly, were evaluated by concurrent and systematic determinations throughout
      the cycle of LH, FSH, estradiol, progesterone, testosterone, prolactin and SHBG
      and in the case of RTR also by ultrasound follow-up. Biphasic estradiol
      secretion, midcycle LH and FSH surge, duration of luteal phase, midluteal
      progesterone values and in the case of RTR, ultrasonic parameters were consistent
      with: (1) normal ovulatory cycles in five RTR; (2) ovulatory cycles with luteal
      phase deficiency in five RTR and two HD patients; (3) anovulatory cycles in one
      RTR and two HD patients. Thus, in HD patients only abnormal cycles of central
      etiology were found, while in RTR, luteal phase deficiency was a very common
      syndrome, in equal percentage with normal ovulatory cycles.

PMID- 1346598
TI  - Effect of the vibratory acoustic stimulation on fetal heart rate patterns of
      premature fetuses.
AB  - The purpose of this study was to examine the heart rate patterns before and after
      a standardized external vibratory acoustic stimulation in a group of 24 healthy
      premature fetuses at 32-35 weeks gestational age. FHR was analysed on line by
      Sonicaid Computer System 8000. A significant increase in the number of
      accelerations and an increase of variation after stimulus were observed. All
      other FHR patterns such as baseline, high and low episodes did not change
      significantly.

PMID- 1346599
TI  - Role of thioridazine in unexplained infertility.
AB  - A total of 452 women with unexplained infertility were selected for the present
      study. From them 310 women were put on thioridazine tablet (5 mg), 1 h after
      dinner from the 8th day of the menstrual cycle to the 18th day in each cycle.
      Coitus was advised about 1-2 h after the drug intake and proper posture was
      advised to the patients. The other 142 patients were given placebo therapy.
      Patients were followed up for pregnancy for 1 year which was confirmed by
      ultrasonographic examination. Ninety-four patients (30.2%) in the study group
      conceived in contrast to 22 (15.42%) in the control group (P less than 0.001).
      Incidence of abortions, congenital malformations and perinatal mortality and mode
      of delivery were not significantly different in the two groups. Thioridazine due
      to anxiolytic effect in low dosage appears to be promising in the treatment of
      unexplained infertility.

PMID- 1346600
TI  - Fetal interlocking: unusual handling of a rare complication.

PMID- 1346601
TI  - Ogilvie's syndrome.
AB  - Four cases of Ogilvie's syndrome (acute colonic pseudo-obstruction) are reported.
      All occurred in the early puerperium following cesarean section and cesarean
      hysterectomy. In three of the patients, the diameter of the distended cecum was
      less than 9.0 cm and so management was conservative while in the fourth patient
      it was more than 9.0 cm, and so surgical intervention was carried out. A cecal
      diameter of 9.0 cm or above is an indication for surgical intervention to prevent
      possible colonic perforation. Other indications for surgery include established
      cecal perforation and failed conservative management. It is important that an
      early diagnosis is made and management instituted in order to prevent
      complications and associated high mortality.

PMID- 1346602
TI  - Laparoscopic management of adnexal torsion during the second trimester.

PMID- 1346603
TI  - Pseudotumor cerebri mimicking hyperemesis gravidarum.

PMID- 1346604
TI  - Prevention of D isoimmunization. ACOG Technical Bulletin number 147--October
      1990.

PMID- 1346605
TI  - Management of isoimmunization in pregnancy. ACOG Technical Bulletin number 148-
      October 1990.
AB  - Isoimmunization is diagnosed by a positive antibody screen and requires
      identification of the specific antigen responsible, titration of the level of
      antibody response, and classification of the antigen into either a clinically
      significant or benign group. The paternal antigen status and zygosity should be
      determined whenever possible. A significant antibody response to an antigen
      associated with erythroblastosis should be monitored at regular intervals by
      obtaining serial titers, and repetitive amniocentesis or fetal blood sampling may
      be required to adequately monitor the fetal condition. Early and continued
      consultation with a perinatologist and a neonatologist who are experts in the
      management of this condition is critical in developing an appropriate therapeutic
      plan that includes proper management at delivery and optimal neonatal support.
      New technologies and expertise now allow better outcome for severely affected
      fetuses.

PMID- 1346606
TI  - Deception. ACOG Committee opinion: Committee on Ethics number 87--November 1990.
AB  - Deception is the deliberate misrepresentation of facts through words or actions
      in order to make a person believe that which is not true. The forms deception can
      take include explicit lying, deception by implication, and deception by omission
      of information that patients need to make decisions in their own regard.
      Deception intended to advantage the physician economically or otherwise at the
      expense of the patient is unethical.

PMID- 1346607
TI  - Uterine motility in patients with bicornuate uterus.
AB  - This study analyzes uterine motility in 12 women with a bicornuate uterus using
      the results of the recordings of endo-uterine pressure, obtained with two balloon
      closed catheters. Seven patients had symmetric uterine cavities, while the rest
      (5 patient) had very dissimilar ones. The registration of the uterine motility
      was carried out during various phases of the cycle and after the administration
      of two drugs (oxitocin and methylergobasine), with the following results: the
      bicornuate uterus has a spontaneous activity similar to that of a normal uterus.
      A similar contractile response was observed in the uteri with two anatomically
      symmetric horns, whereas a dissimilar response was typical of the uteri with
      marked anatomic differences between the two horns.

PMID- 1346608
TI  - Developmental potential.
AB  - In summary (and probably to no one's genuine surprise), it seems clear that some
      of the key themes in the mechanisms employed during development reiterate
      themselves throughout the animal kingdom. Yet, as our understanding becomes more
      refined, new and beguiling observations point to unique aspects of each
      developmental program. The concentration and absolute position of a variety of
      positional signaling molecules is likely to be very important in determinative
      events (establishment of the anteroposterior positioning in a field as in retinal
      development, establishment or enactment of a hox code, and selector gene
      regulation through gradients in Drosophila). Appropriate signalling responses are
      virtually certain to depend critically on the appropriate expression of each
      component of cellular signal transduction pathways (initiated by the activation
      of cell-surface receptor protein kinases to finally eliciting gene expression
      changes through the differential activity of specific transcription factors). The
      important biochemical details of transcription factor activation of specific
      respondent genes may be either simpler (as indicated from the murine/Drosophila
      domain swap experiments) or more complicated (from the responses of mim-1 to
      cellular versus viral myb proteins) than we had heretofore anticipated.

PMID- 1346609
TI  - The polyhomeotic gene of Drosophila encodes a chromatin protein that shares
      polytene chromosome-binding sites with Polycomb.
AB  - The Polycomb group (PcG) genes in Drosophila melanogaster are required for
      maintenance of correct spatial expression of homeotic genes, and their products
      are thought to form either a regulatory network or act as a multimeric complex.
      Recently, it has been suggested that because of homology between Polycomb (Pc)
      and Su(var)205, PcG genes encode chromatin proteins required for the maintenance
      of a determined state in chromatin. The polyhomeotic (ph) gene is a member of the
      PcG of genes. We present DNA sequence of a ph cDNA, which encodes a 169-kD
      protein with a single putative zinc finger, a serine/threonine-rich region, and
      has glutamine repeats, suggesting that ph is a DNA-binding protein. Polyclonal
      antisera directed against ph protein bind to approximately 80 sites on polytene
      chromosomes. Most of these sites appear to be the same as those recognized by
      antibodies to Pc protein. ph protein binds to insertion sites of constructs
      containing DNA from the bithoraxoid (bxd) region of the Bithorax complex, showing
      that ph binding to chromatin is DNA dependent. The same bxd constructs are
      recognized by Pc protein, strongly supporting the hypothesis that ph and Pc
      interact directly.

PMID- 1346610
TI  - Effect of overproduction of heat shock chaperones GroESL and DnaK on human
      procollagenase production in Escherichia coli.
AB  - The effect of overexpression of the heat shock chaperone genes dnaK and groESL on
      heterologous protein production in Escherichia coli was examined, using a set of
      related human procollagenase proteins. A diverse range of effects on protein
      solubility, secretion, and accumulation was observed, and these effects were
      highly dependent on the particular chaperone/procollagenase pairing involved.
      Both chaperones caused a large increase in the apparent solubility of a fusion of
      the LamB signal peptide to procollagenase. GroESL had no effect on the
      accumulation of mature (secreted) procollagenase, while DnaK suppressed secretion
      considerably. In the absence of a signal peptide, overexpression of either
      chaperone resulted in a dramatic increase in both solubility and accumulation of
      procollagenase. The 10-fold increase in accumulation was associated with an
      increase in in vivo protein half-life.

PMID- 1346611
TI  - Insulin activation of acetyl-CoA carboxylase accompanied by inhibition of the 5'
      AMP-activated protein kinase.
AB  - The activity of acetyl-CoA carboxylase (ACC), a rate-limiting enzyme of fatty
      acid biosynthesis and malonyl-CoA production, can be regulated by several
      mechanisms, including multisite covalent phosphorylation, both in vitro and in
      intact cells. Evidence has been presented by others to indicate that a 5'-AMP
      activated protein kinase (AMPK) is likely the major regulatory kinase active on
      ACC. While insulin is known to activate ACC in several cell types, accompanied by
      changes in ACC phosphorylation, the mechanism underlying this activation has been
      obscure. In the present study, we have examined, in Fao hepatoma cells, the
      effects of insulin on ACC and AMPK activity, the latter measured with a synthetic
      peptide corresponding to one of the phosphorylation sites on ACC for AMPK. Our
      results show that insulin leads to inhibition of kinase activity prior to the
      onset of ACC activation; the peak of maximal kinase inhibition (approximately 35%
      at 10 min) is seen to precede the onset of ACC activation (20 min). The
      inhibition of kinase activity due to insulin is observed both in the absence and
      presence of varying stimulating concentrations of added 5'-AMP. Both kinase
      inhibition and ACC activation display similar insulin sensitivity (A50 0.3 nM).
      Preservation of this insulin-induced kinase inhibition requires the presence of
      protein phosphatase inhibitors in the cell lysis buffer, suggesting that AMPK
      itself might be regulated by insulin-stimulated changes in kinase
      phosphorylation. Taken together, these data are consistent with the hypothesis
      that the 5'-AMP-activated protein kinase is a regulated component of the insulin
      signal transduction pathway and may be the major target for insulin regulation of
      ACC.

PMID- 1346612
TI  - Brain somatostatin receptor-G protein interaction. G alpha C-terminal antibodies
      demonstrate coupling of the soluble receptor with Gi(1-3) but not with Go.
AB  - Somatostatin (SST) receptors activate potassium channels, stimulate protein
      phosphatases, inhibit adenylate cyclase and close calcium channels. These
      multiple effects are controlled by guanine nucleotide binding (G) proteins of the
      pertussis toxin-sensitive Gi and Go types. In the present study we have
      identified the G proteins coupling with brain SST receptors. To this end, brain
      SST receptors were solubilized in G-protein coupled form. Binding of the SST
      analogue MK 678 to the solubilized receptor was completely inhibited by guanosine
      5'-O-thiotriphosphate (IC50 = 100 nM), reflecting decreased receptor affinity for
      agonist following uncoupling of the receptor and G protein(s). Antibodies raised
      against specific COOH-terminal peptides of the G proteins Gi(1-3), Go, and Gz
      were used to probe for SST receptor-G protein coupling in this system. Antibodies
      binding to the COOH-terminal regions of Gi1 and Gi2 (antibody AS) and Gi3
      (antibody EC) inhibited binding of 125I-MK 678 (75 pM) by 57 +/- 4% and 48 +/-
      5%, respectively. The effects of these antibodies were concentration-dependent
      and additive, such that in combination AS and EC completely inhibited binding.
      Antibodies binding to the COOH-terminal region of Go (GO) and Gz (QN) did not
      affect binding of 125I-MK 678, indicating that neither Go nor Gz are associated
      with the brain SST receptor. Prelabeling of the receptor with 125I-MK 678 prior
      to addition of antibody induced the formation of a "locked conformation" of the
      agonist-bound receptor-G protein complex which was insensitive to antibody. In
      conclusion, Gi1 and/or Gi2 and Gi3 are coupled in approximately equal proportions
      to the brain 125I-MK 678-binding SST receptor, accounting for all of the G
      protein coupling of this receptor.

PMID- 1346613
TI  - Genetic cause of leukocyte adhesion molecule deficiency. Abnormal splicing and a
      missense mutation in a conserved region of CD18 impair cell surface expression of
      beta 2 integrins.
AB  - Patients with leukocyte adhesion molecule (CD11/CD18, beta 2 integrins)
      deficiency have structural defects in the common beta subunit (CD18), which
      prevent heterodimer formation and normal cell surface expression of these
      receptors, leading to life-threatening bacterial infections. To elucidate the
      nature of these defects in a patient with partial (type II) deficiency, abnormal
      CD18 cDNA clones were isolated, using the polymerase chain reaction to amplify
      the patient's B cell-derived cDNAs. Sequence analysis revealed two mutant
      alleles. cDNA clones, representing a maternal allele, contained both a 12-base
      pair insertion resulting in an in-frame addition of four amino acids between P247
      and E248 and a C1756----T nucleotide transition, resulting in an R586----W
      substitution in the normal CD18 protein. The inframe insertion arose by a single
      nucleotide C----A transversion in the 3' terminus of an intron, generating
      aberrant splice acceptor site. Other cDNA clones contained an A1052----G
      nucleotide transition not present in either parent which resulted in an N351----S
      substitution. To determine the functional importance of these changes, cDNA
      encoding a normal alpha chain (CD11b) was cotransfected into COS with CD18 cDNAs
      encoding for wild-type, maternal mutant allele, or CD18 containing N351----S
      substitution. Immunostaining of transfectants with anti-CD18 monoclonal
      antibodies revealed no cell surface expression of the maternal mutant CD18, and
      22% surface expression of N351----S CD18. Both the insertion and the N351----S
      mutations occurred in a 250 amino acid extracellular region of CD18 that is
      highly conserved among beta integrins supporting a role for this region in
      heterodimer formation.

PMID- 1346614
TI  - Primary care for HIV infection.

PMID- 1346615
TI  - NH2-terminal globular domain of human platelet glycoprotein Ib alpha has a
      methionine 145/threonine145 amino acid polymorphism, which is associated with the
      HPA-2 (Ko) alloantigens.
AB  - The glycoprotein (GP) Ib/IX complex, a prominent platelet GP complex, is the
      primary receptor for vWF. Previously, we have established that an antigenic
      polymorphism of platelets, the HPA-2 or Ko alloantigen system, is located on the
      45-kD amino-terminal globular domain of GPIb alpha. With the polymerase chain
      reaction, we have amplified two segments of the GPIb alpha gene coding for the
      first 382 amino acids of two HPA-2a and two HPA-2b homozygous individuals.
      Nucleotide sequence analysis revealed as the only difference a C-T polymorphism
      at position 434 of the coding region for the mature protein. This base change
      results in a substitution of threonine (ACG) in HPA-2a (Kob) to methionine (ATG)
      in HPA-2b (Koa) at amino acid position 145. The C-T polymorphism is reflected in
      a difference in restriction enzyme recognition, resulting in an Aha 2-site in the
      HPA-2b allele and a SfaN1 site in the HPA-2a allele. Restriction fragment length
      polymorphism analysis of the amplified DNA of 3 HPA-2(a-,b+), 2 HPA-2(a+,b+), and
      11 HPA-2(a+,b-) donors showed that these restriction sites were associated with
      the HPA-2 alleles. DNA-typing for the HPA-2 alloantigen system on genomic DNA
      obtained from a small number of cells may be applied for determining the genotype
      of a fetus from an immunized mother or of severely thrombocytopenic patients.

PMID- 1346616
TI  - Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered
      cobalamin affinity that causes mut- methylmalonic aciduria.
AB  - Distinct genotypic and phenotypic forms of methylmalonyl CoA mutase (MCM)
      apoenzyme deficiency can be delineated by biochemical analysis of mutant
      fibroblasts. One form, designated mut-, expresses a phenotype in which residual
      enzyme activity is evident in cultured cells exposed to high concentrations of
      hydroxycobalamin. We describe cloning of an MCM cDNA from cells exhibiting a mut-
      phenotype and characterization of the mutant gene product overexpressed in
      primary muto human fibroblasts and Saccharomyces cerevisiae. Three novel base
      changes were observed. Recombinant clones containing one of these base changes
      (G717V) express four characteristics of the mut- phenotype: failure to constitute
      [14C]propionate incorporation activity in fibroblasts assayed under basal cell
      culture conditions, constitution of [14C]propionate incorporation activity in
      fibroblasts stimulated with 0.1-1.0 micrograms/ml hydroxycobalamin, interallelic
      complementation with alleles bearing an R93H mutation, and an apparent Km
      (adenosylcobalamin) 1,000-fold higher than normal. These results demonstrate that
      the G717V mutation produces the mut- phenotype and localizes determinants for
      adenosylcobalamin binding near the carboxyl terminus of MCM.

PMID- 1346617
TI  - Identification of three mutant alleles of the gene for mitochondrial acetoacetyl
      coenzyme A thiolase. A complete analysis of two generations of a family with 3
      ketothiolase deficiency.
AB  - 3-Ketothiolase deficiency (3KTD) stems from a deficiency of mitochondrial
      acetoacetyl-coenzyme A thiolase (T2). We analyzed the molecular basis of 3KTD in
      two generations of a family. A boy (patient 2, GK04), his father (patient 1,
      GK05), his mother, and his brother were studied; three mutant alleles of T2 gene
      were identified. Patient 1 is a compound heterozygote: one allele has a point
      mutation of G to A at position 547 on his T2 cDNA, causing Gly150 to Arg
      substitution of the mature T2 subunit, and the other allele has GT to TT
      transition at the 5' splice site of intron 8, causing exon 8's skipping of the T2
      cDNA. Patient 2 is also a compound heterozygote: one allele inherited from his
      mother has AG to CG transition at the 3' splice site of intron 10, causing exon
      11's skipping of the T2 cDNA, and the other allele derived from patient 1 has the
      G to A mutation (Gly to Arg). The brother of patient 2 is an obligatory carrier
      with the mutant allele causing the exon 8 skipping. This report seems to be the
      first complete molecular definition of 3KTD at the gene level.

PMID- 1346619
TI  - A common precursor for CD4+ T cells producing IL-2 or IL-4.
AB  - To investigate whether CD4+ T cells are predetermined to produce a given pattern
      of lymphokines, we have used a culture system that allows the controlled
      induction of either IL-2- or IL-4-producing CD4+ T cells. Single, freshly
      isolated murine CD4+ T cells were activated with Con A, rIL-2, and APC; the
      developing clones were split and then cultured for an additional 14 days with
      either rIL-2 alone or with rIL-2 and anti-CD3 stimulation. Subclones expanded in
      the presence of rIL-2 alone produced predominantly IL-2, although subclones
      derived from the same precursor and expanded in the presence of rIL-2 and a
      mitogenic antibody to CD3 released predominantly IL-4. Subclones expanded for 2
      wk in the presence of rIL-2 plus a mitogenic mAb to CD3 released up to 60 times
      more IL-4 but only 1/90 the amount of IL-2 released by subclones derived from the
      same precursor cell and expanded with rIL-2. Both phenotypes can be derived from
      IL-2-producing precursor cells. These results demonstrate that IL-2-producing
      clones can be derived from the same cells as IL-4-producing clones and are most
      consistent with the view that the IL-2-producing Th1 or the IL-4-producing Th2
      phenotype of a T cell clone is acquired during T cell differentiation and is not
      secondary to the expansion of distinct subpopulations that are predetermined to
      produce a specific cytokine pattern.

PMID- 1346620
TI  - T cell surface molecules regulating noncognate B lymphocyte activation. Role of
      CD2 and LFA-1.
AB  - A central event in humoral responses is the Ag-mediated interaction of Th cells
      and B cells. This interaction leads to the activation of both cell types and
      results in cytokine secretion by the T cells and proliferation and secretion of
      Ig by the B cells. The proliferative and differentiative responses of B cells are
      dependent on contact-mediated signals and cytokines provided by the activated Th
      cells. Although the role of cytokines in B cell activation and differentiation is
      understood, the nature of the signals delivered by the activated Th cells and the
      molecules involved in this process are not known. In this study we have examined
      Ag-mediated "cognate" T-B cell interactions as well as B cell activation induced
      by contact with preactivated and fixed Th lymphocytes. Our results indicate that
      both the T cell surface molecules lymphocyte function associated Ag-1 and CD2 are
      important in the activation of T cells by Ag presented by B lymphocytes. This
      indicates that B cells have similar characteristics as other APC. However, once
      the T cells are activated, contact-mediated stimulation of resting B lymphocytes
      (the noncognate phase) is dependent on CD2 but not lymphocyte function associated
      Ag-1. Two lines of evidence indicate this; first, it is inhibited by blocking of
      CD2 on the T cells and, second, such stimulation is not efficiently mediated by a
      CD2- Th cell line. Thus, CD2 plays an obligatory role at several discrete stages
      of T cell-mediated activation of resting B lymphocytes.

PMID- 1346618
TI  - Neutrophil adherence to isolated adult cardiac myocytes. Induction by cardiac
      lymph collected during ischemia and reperfusion.
AB  - Canine neutrophils can be induced to adhere in vitro to isolated adult cardiac
      myocytes by stimulation of the neutrophils with chemotactic factors such as
      zymosan-activated serum (ZAS) only if the myocytes have been previously exposed
      to cytokines such as interleukin 1 (IL-1) or tumor necrosis factor-alpha. These
      cytokines induce synthesis and surface expression of intercellular adhesion
      molecule-1 (ICAM-1) on the myocyte, and neutrophil adhesion is almost entirely
      CD18 and ICAM-1 dependent. The present study examines cardiac-specific lymph
      collected from awake dogs during 1-h coronary occlusion and 3 d of reperfusion
      for its ability to induce both ICAM-1 expression in cardiac myocytes, and
      neutrophil-myocyte adherence. Reperfusion lymph induced ICAM-1 expression in
      isolated myocytes, and myocyte adherence to ZAS-stimulated neutrophils that was
      completely inhibited by anti-CD18 and anti-ICAM-1 monoclonal antibodies. This
      activity peaked at 90 min of reperfusion and persisted for up to 72 h.
      Preischemic lymph was not stimulatory. IL-1 appeared not to be a stimulating
      factor in lymph in that dilutions of lymph were found to inhibit the stimulatory
      effects of recombinant IL-1 beta. However, investigation of interleukin 6 (IL-6)
      revealed that recombinant IL-6 stimulated myocyte adhesiveness for ZAS-stimulated
      neutrophils (ED50 = 0.002 U/ml) and expression of ICAM-1 by isolated myocytes. IL
      6 neutralizing antibody markedly reduced the ability of reperfusion lymph to
      stimulate adhesion and ICAM-1 expression, and estimates of levels of IL-6 in
      reperfusion lymph ranged from 0.035 to 0.14 U/ml. These results indicate that
      cytokines capable of promoting neutrophil-myocyte adhesion occur in extracellular
      fluid during reperfusion of ischemic myocardium, and that one of these cytokines
      is IL-6. Neutrophil-myocyte adhesion may be of pathogenic significance because it
      may enhance the cytotoxic activity of the neutrophil.

PMID- 1346622
TI  - Plasma cell-regulated polyadenylation at the Ig gamma 2b secretion-specific
      poly(A) site.
AB  - We found that the sequences downstream of the Ig gamma 2b secretory-specific
      (sec) poly(A) site play an important role in the preferential production of sec
      Ig mRNA during plasma B cell development. The Ig gamma 2b mRNA production in a
      deletion mutant (delta-Kpn) lacking the Ig sec poly(A) site and downstream
      consensus element (dsc) has been previously shown to default to the use of the
      downstream membrane-specific (mb) poly(A) site. In this study restoration of the
      Ig sec poly(A) site and dsc to the delta-Kpn gene causes a significant increase
      in the use of the sec poly(A) site vs mb poly(A) site in stable transfectants of
      plasma but not memory B cell tumors, indicating plasma cell-specific recognition
      of the Ig sec dsc. Restoration of the poly(A) cleavage site alone to delta-Kpn
      did not restore regulation. Substitution of an SV40 downstream poly(A) element
      for the Ig dsc in the delta-Kpn gene also does not restore regulation. The data
      further indicate that although the Ig dsc is clearly very important in the plasma
      cell-regulated expression, the difference in the processing ratios of the
      restored vs the intact Ig gamma 2b gene in plasma cells suggests that there are
      other yet to be defined sequences that may also play a role in the intact gene.
      Insertion of a 130-nucleotide segment of the gene containing the Ig sec poly(A)
      site and dsc into a heterologous, guanosyl phosphotransferase gene resulted in
      plasma cell-regulated polyadenylation of the sec poly(A) site. Neither the mb nor
      the SV40 early poly(A) sites and their respective dscs, in similar gpt chimeras,
      were regulated. Therefore the region downstream of the Ig sec poly(A) site plays
      an essential role in regulating polyadenylation at the sec poly(A) site in plasma
      cells but not memory cells. A model involving a plasma cell-specific recognition
      factor for the Ig sec dsc is presented.

PMID- 1346621
TI  - CD2 expression correlates with proliferative capacity of alpha beta + or gamma
      delta + CD4-CD8- T cells in lpr mice.
AB  - The T lymphocytes that accumulate in vast numbers in the lymphoid tissues of
      lpr/lpr (lpr) mice express a TCR-alpha beta that is polyclonally rearranged, and
      yet is devoid of surface CD4 or CD8 (CD4-8-) as well as CD2. lpr CD2- alpha beta
      + CD4-8- T cells exhibit an apparent block in signal transduction, in that when
      activated they produce little or no IL-2 and proliferate minimally in the absence
      of exogenous IL-2. In contrast to the predominant hyporesponsive alpha beta + CD4
      8- T cells, we observe that a minor subset (1 to 2%) of lpr lymph node CD4-8-
      cells expresses a TCR-gamma delta and can proliferate upon activation with PMA
      and ionomycin in the absence of exogenous IL-2. Furthermore, these responsive
      gamma delta T cells express surface CD2. The functional and phenotypic
      distinctions of lpr gamma delta T cells led us to identify an analogous minor (4
      to 10%) subset of alpha beta + CD4-8- cells in lpr thymus and lymph nodes that
      does express CD2. Similar to the gamma delta subset, these CD2+ alpha beta + CD4
      8- cells are also capable of proliferation and IL-2 production. Thus the capacity
      for IL-2 production and proliferation by a small proportion of lpr CD4-8- T
      cells, either alpha beta + or gamma delta +, correlates with their expression of
      surface CD2. This correlation is supported by the observation that the lpr liver
      contains actively cycling alpha beta + CD4-8- lymphocytes that are strikingly
      enriched for CD2 expression. Consequently, unlike the vast proportion of abnormal
      lpr CD2- CD3+ CD4-8- cells, the CD2+ CD3+ CD4-8- T cells may not express the
      basic lpr defect, or else are not affected by its presence. These studies suggest
      that expression of the lpr abnormality may be restricted to a particular T cell
      lineage. This functional correlation with CD2 expression may be more broadly
      applicable to phenotypically similar subsets of normal thymocytes, and possibly
      peripheral tolerized T lymphocytes.

PMID- 1346623
TI  - A biphasic effect of noradrenaline on renin release from rat juxtaglomerular
      cells in vitro is mediated by alpha 1- and beta-adrenoceptors.
AB  - The direct effect of noradrenaline on renin release from juxtaglomerular (JG)
      cells in vitro were investigated in a dynamic superfusion system of dispersed rat
      renal cortical cells. At low concentrations (1-100 nmol/l), noradrenaline
      stimulated renin release in a dose-dependent manner, while at higher
      concentrations (0.1-1 mmol/l) it inhibited renin release. The stimulatory effect
      of 0.1 mumol noradrenaline/l was completely blocked by a beta-adrenoceptor
      antagonist, propranolol (0.1 mumol/l). When applied at concentrations of 1
      mumol/l or 10 mumol/l, noradrenaline had no consistent effect on renin release,
      although 10 mumol noradrenaline/l had an inhibitory effect in the presence of
      propranolol (0.1 mumol/l). The inhibitory effect of noradrenaline (0.1 mmol/l)
      was converted to a stimulatory effect by the addition of an alpha 1-adrenoceptor
      antagonist (bunazosin, 1 mumol/l), but was not altered by the addition of an
      alpha 2-adrenoceptor antagonist (yohimbine, 1 mumol/l). These results indicate
      that low concentrations of noradrenaline directly stimulate renin release from JG
      cells by the activation of beta-adrenoceptors, while high concentrations of
      noradrenaline inhibit renin release by the activation of alpha 1-adrenoceptors.
      Accordingly, a dynamic balance may exist between beta-adrenergic stimulation and
      alpha 1-adrenergic depression of renin release.

PMID- 1346624
TI  - Examination of parameters influencing [3H]MK-801 binding in postmortem human
      cortex.
AB  - [3H]MK-801 binding was used as an index of the glutamate receptor N-methyl-D
      aspartate-subtype channel to examine the influence of gender, age, mode of death
      (agonal status), interval between death and autopsy (postmortem delay), and time
      in storage at -70 degrees C in well washed homogenate preparations from
      postmortem human frontal cortex. Basal binding and the modulatory effects of
      glutamate, glycine, spermidine, and zinc were examined with respect to these
      variables. Basal binding was sensitive to agonal status, being higher in sudden
      death cases. The effect of added glutamate and glycine was sensitive to age, with
      a trend toward lower binding with increasing age. The effect of added spermidine
      alone was sensitive to storage time at -70 degrees C, the binding being higher
      with longer storage time. The effect of added zinc was also sensitive to
      postmortem delay, with zinc causing a greater reduction in binding with shorter
      postmortem delays. Thus, with the exception of gender, all variables examined
      influenced [3H]MK-801 binding, highlighting the attention that should be given to
      these factors in postmortem studies in normal and diseased human subjects.

PMID- 1346625
TI  - Agonist-stimulated inositol polyphosphate formation in cerebellum.
AB  - The accumulation of inositol polyphosphates in the cerebellum in response to
      agonists has not been demonstrated. Guinea pig cerebellar slices prelabeled with
      [3H]inositol showed the following increases in response to 1 mM serotonin: At 15
      s, there was a peak in 3H label in the second messenger inositol 1,4,5
      trisphosphate [Ins(1,4,5)P3], decreasing to a lower level in about 1 min. The
      level of 3H label in the putative second-messenger inositol 1,3,4,5
      tetrakisphosphate [Ins(1,3,4,5)P4] increased rapidly up to 60 s and increased
      slowly thereafter. The accumulation of 3H label in various inositol phosphate
      isomers at 10 min, when steady state was obtained, showed the following increases
      due to serotonin: inositol 1,3,4-trisphosphate [Ins(1,3,4)P3], eight-fold;
      Ins(1,3,4,5)P4, 6.4-fold; Ins(1,4,5)P3, 75%; inositol 1,4-bisphosphate
      [Ins(1,4)P2], 0%; inositol 3,4-bisphosphate, 100%; inositol 1-phosphate/inositol
      3-phosphate, 30%; and inositol 4-phosphate, 40%. [3H]Inositol 1,3-bisphosphate
      was not detected in controls, but it accounted for 7.2% of the total inositol
      bisphosphates formed in the serotonin-stimulated samples. The fact that serotonin
      did not increase the formation of Ins(1,4)P2 could be due to the fact that
      Ins(1,4)P2 is rapidly degraded or that Ins(1,4,5)P3 is metabolized primarily by
      Ins(1,4,5)P3-3'kinase to form Ins(1,3,4,5)P4. In the presence of pargyline (10
      microM), [3H]Ins(1,3,4,5)P4 and [3H]Ins(1,3,4)P3 levels were increased, even at 1
      microM serotonin. Ketanserin (7 microM) completely inhibited the serotonin
      effect, indicating stimulation of serotonin2 receptors. Quisqualic acid (100
      microM) also increased the levels of [3H]Ins(1,4,5)P3, [3H]Ins(1,3,4,5)P4, and
      [3H]Ins(1,3,4)P3, but the profile of these increases was different.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1346626
TI  - Involvement of dopamine D1 and D2 receptors in the regulation of proenkephalin
      mRNA abundance in the striatum and accumbens of the rat brain.
AB  - The effects of short-term treatment (6 h) with selective D1 or D2 agonists and
      antagonists on the mRNA for proenkephalin in the medial and anterior aspects of
      the caudate-putamen and the nucleus accumbens were assessed by in situ
      hybridization histochemistry. Proenkephalin mRNA abundance was significantly
      changed in the striatum and accumbens in response to D2 receptor manipulation. D2
      blockade with haloperidol or raclopride increased, whereas D2 stimulation with LY
      171555 (D2 agonist) decreased, striatal and accumbens proenkephalin mRNA
      abundance. Antagonism of D1 receptor activity with SCH-23390 significantly
      decreased proenkephalin mRNA abundance in all brain regions. Concurrent
      administration of the D1 agonist SKF-38393 prevented the SCH-23390 effect in all
      brain areas. The data demonstrate that acute treatment with dopaminergic D2
      agonists and antagonists affects proenkephalin mRNA abundance in the striatum and
      accumbens via a D2 receptor mechanism, consistent with the concept that D2
      receptor function inhibits the synthesis of the mRNA encoding the enkephalin
      peptides. Moreover, D1 receptor activity, directly or indirectly, exerts
      modulatory effects on proenkephalin mRNA abundance in the striatum and nucleus
      accumbens.

PMID- 1346627
TI  - Pertussis toxin in the A10 region increases dopamine synthesis and metabolism.
AB  - Inhibitory regulation of dopamine neurons is mediated by dopamine autoreceptor
      and gamma-aminobutyric acidB receptor opening of potassium channels. Increased
      potassium conductance by either receptor is G protein dependent. To evaluate the
      role of G proteins in vivo, pertussis toxin (PTX) was microinjected into the A10
      dopamine region and changes in dopamine metabolism and synthesis measured. PTX
      produced an elevation in dopamine metabolism and synthesis in the A10 region and
      nucleus accumbens for up to 4 days after injection. By day 7 the levels of the
      dopamine precursor and metabolites had returned to normal. A less consistent
      increase was also measured in the A9 dopamine region and the prefrontal cortex.
      Although dopamine synthesis and metabolism had returned to normal by day 7, the
      in vitro ADP-ribosylation of G proteins in the A10 region by PTX remained
      depressed by approximately 50% from day 1 to day 14 after administration,
      returning to normal by day 30. The data suggest that in vivo ribosylation of G
      proteins may lead to a short-term attenuation of the tonic inhibitory control of
      dopamine neurons, which can be compensated for by PTX-insensitive mechanisms.

PMID- 1346628
TI  - Gamma-glutamyl transpeptidase activity in brain microvessels exhibits regional
      heterogeneity.
AB  - Brain microvessels form a tight blood-tissue permeability barrier and express
      high levels of specific enzymes, including gamma-glutamyl transpeptidase (GGTP).
      This differentiation is thought to be induced by perivascular astrocytes. By
      using histochemical methods, we found that the percentage of GGTP-positive
      vessels varied considerably in different areas of rat brain. Enzyme activity was
      not found in the pineal gland or the median eminence, where the blood-brain
      barrier is not expressed. In areas where the blood-brain barrier is expressed,
      the percentage of GGTP-positive vessels varied from 8% in the optic nerve to 100%
      in the anterior commissure. The neocortex showed a lower percentage of GGTP
      positive vessels (2-15%) than anterior olfactory nucleus (42%), subiculum (70%),
      hippocampus (48%), and striatum (50-58%). Alkaline phosphatase, another brain
      microvessel-enriched enzyme, did not show these marked regional differences. The
      morphometric histochemical results were verified by enzymatic assays in
      homogenates of different regions from rat and bovine brain and in microvessel
      preparations of bovine putamen and neocortex. During the postnatal development of
      rat brain, the difference between neocortex and striatum appeared after day 20.
      The regional heterogeneity of brain microvessels may be caused by astrocytic
      heterogeneity and reflect regional heterogeneity in microvascular function.

PMID- 1346629
TI  - Expression of catecholamine-synthesizing enzymes in paraganglionic and ganglionic
      cells in the laryngeal nerves of the rat.
AB  - The rat recurrent and superior laryngeal nerves with adjacent connective tissue
      were examined by immunohistochemical techniques for localization of the
      catecholamine-synthesizing enzymes tyrosine hydroxylase, dopamine-beta
      hydroxylase and phenylethanolamine-N-methyltransferase. Most of the cells in the
      paraganglia of the recurrent and superior laryngeal nerves showed an intense
      tyrosine hydroxylase-like immunoreactivity. A few paraganglionic cells exhibited
      dopamine-beta-hydroxylase-like immunoreactivity while none of the cells displayed
      phenylethanolamine-N-methyltransferase-like immunoreactivity. Some of the
      ganglionic cells in the recurrent and superior laryngeal nerves showed dopamine
      beta-hydroxylase-like immunoreactivity whilst these cells never showed tyrosine
      hydroxylase- or phenylethanolamine-N-methyltransferase-like immunoreactivity. The
      arterioles were supplied with plexuses of nerve fibres showing tyrosine
      hydroxylase- and dopamine-beta-hydroxylase-like immunoreactivity. The results
      indicate that dopamine is the major catecholamine located in the laryngeal nerve
      paraganglia and show that ganglionic cells in the recurrent and superior
      laryngeal nerves show immunolabelling for one of the enzymes in the catecholamine
      synthetic pathway, dopamine-beta-hydroxylase.

PMID- 1346630
TI  - Terminal Schwann cells elaborate extensive processes following denervation of the
      motor endplate.
AB  - Terminal Schwann cells, when stained for S100 (a calcium binding protein), can be
      seen to cap motor axons at the neuromuscular junction. Within days of denervation
      the Schwann cells begin to stain for the low affinity nerve growth factor
      receptor, but remain Thy-1 negative, and elaborate fine processes. These
      processes become longer and more disorganized over weeks, and cells positive for
      S100 and nerve growth factor receptor migrate into the perisynaptic area.
      Reinnervation results in a withdrawal of the processes. The morphology and
      location of terminal Schwann cells seems to depend on axonal contact. The spread
      of Schwann cells and their processes away from the synaptic zone following
      denervation, implies that these cells do not target axons directly to the
      endplate.

PMID- 1346631
TI  - Development of multidrug resistance in a primitive neuroectodermal tumor cell
      line.
AB  - Drug resistance remains a formidable obstacle to the successful treatment of
      pediatric primitive neuroectodermal tumors. Resistance to chemotherapeutic agents
      may be related, in part, to expression of the multidrug resistance gene 1 (MDR1).
      The protein product of this gene, P-glycoprotein, confers resistance to multiple
      unrelated antineoplastic drugs. The cell line DAOY, derived from a primitive
      neuroectodermal tumor, was used as an in vitro model to examine the development
      of drug resistance. Cell lines resistant to actinomycin D were developed by the
      growth of DAOY in increasing concentrations of the drug. The IC50 (concentration
      of drug needed to induce a 50% reduction in cell growth) of the resultant lines
      to actinomycin D was more than 10 times that of the parental line. The resistant
      lines were cross-resistant to VP-16 (etoposide), despite lack of previous
      exposure to this drug. The resistance to actinomycin D was attenuated in the
      presence of verapamil, a known inhibitor of P-glycoprotein. The MDR1 gene was not
      expressed by the parental DAOY line at the messenger ribonucleic acid (RNA) and
      protein level. Expression of the MDR1 gene was documented in the resistant lines
      by RNA blot and immunoblot techniques. These results suggest that exposure to
      chemotherapeutic drugs can induce classical multidrug resistance in primitive
      neuroectodermal tumors.

PMID- 1346632
TI  - Multidrug resistance gene expression in pediatric primitive neuroectodermal
      tumors of the central nervous system.
AB  - Pediatric primitive neuroectodermal tumor (PNET) is a malignancy of the central
      nervous system currently treated with surgery, radiation therapy, and
      chemotherapy. Despite aggressive management, tumors recur in almost one-half of
      all patients. Drug resistance of tumor cells may, in part, explain the poor
      outcome. Resistance to chemotherapeutic agents may be related to expression of
      the multidrug resistance gene (MDR1) and its protein product, P-glycoprotein. The
      role of MDR1 in 16 instances of PNET was investigated using Western blot analysis
      to detect the expression of P-glycoprotein, messenger ribonucleic acid (mRNA),
      polymerase chain reaction to detect MDR1 mRNA expression, and Southern blot
      analysis to assess gene amplification. Analysis of proteins extracted from 15
      tumors revealed that two of the 15 patients expressed detectable levels of P
      glycoprotein. Polymerase chain reaction of ribonucleic acid from 12 PNET's
      revealed that six of the 12 patients (four of 10 de novo tumors and both
      recurrent tumors) expressed MDR1 mRNA. Southern blot analysis of deoxyribonucleic
      acid from 16 PNET's revealed no evidence of MDR1 amplification in any tumor. This
      is the first report of MDR1 expression in pediatric brain tumors. These data
      suggest a possible role for MDR1 in de novo and acquired drug resistance in
      PNET's.

PMID- 1346633
TI  - Extended follow-up of peripheral neuropathy in patients with AIDS and AIDS
      related complex treated with dideoxyinosine.
AB  - Neuropathic complaints were frequently observed in a Phase I study of
      dideoxyinosine (ddI) in 44 patients with AIDS and AIDS-related complex. Ten
      patients (23%) were thought to have a ddI-related peripheral neuropathy. The
      symptoms were primarily sensory, and there was limited motor involvement. The
      sensory symptoms improved in all patients with discontinuation of ddI. Some
      patients tolerated reintroduction of ddI at lower doses without significant
      recurrence of the neuropathic symptoms. Although the neuropathy was usually seen
      in patients taking higher doses of ddI than used in current treatment protocols,
      clinicians must be aware of this potential toxicity as more human
      immunodeficiency virus-infected patients are being treated with ddI.

PMID- 1346634
TI  - A mechanism of immune escape by slow-replicating HIV strains.
AB  - Strains of human immunodeficiency virus (HIV) differ greatly in their ability to
      replicate in T4 cells. Fast-replicating strains are observed during the early and
      late stages of HIV infection, while slow-replicating strains prevail during the
      intermediate, latent, stage. The prevalence of slow-replicating strains has been
      attributed to these strains' ability to escape the immune response. However, how
      these strains are able to avoid being eliminated by an immune response for
      several years has not been explained. Recent experiments indicate that HIV may be
      selectively transferred from infected macrophages to T4 cells specific for HIV
      antigens. Thus, HIV may preferentially infect those T4 cells necessary for
      generating a protective immune response. To determine the conditions under which
      an HIV-specific immune response can be blocked, we developed a mathematical model
      incorporating the process of viral transfer from infected macrophages to HIV
      specific T4 cells along with the known processes of macrophage-T4 interaction,
      immune stimulation, and viral infection of T4 cells and macrophages. Our model
      shows that the mechanism of viral transfer to HIV-specific T4 cells can allow
      slow-replicating strains of HIV to escape immune response under conditions in
      which an immune response occurs against fast-replicating strains. The model also
      suggests that in addition to slow replication, the ability to reduce or block T
      cell activation may be an important characteristic of escape mutants.

PMID- 1346635
TI  - 5-Hydroxytryptamine receptor activity of the dopamine receptor agonist fenoldopam
      in canine tracheal smooth muscle.
AB  - Fenoldopam is a new vasodilator undergoing clinical trials for the treatment of
      hypertensive emergencies. Its pharmacologic effects result from activation of
      vascular dopamine-1 receptors. In canine tracheal smooth muscle strips,
      fenoldopam caused a concentration- and calcium-dependent increase in tension,
      which was not antagonized by atropine, indomethacin or the dopamine-1 receptor
      antagonist, SCH 23390. The EC50 (1.89 x 10(-6) M) exceeded that of serotonin or
      acetylcholine (8.38 x 10(-8) and 8.25 x 10(-8) M, respectively). Maximum tension
      was similar for fenoldopam and serotonin (11.6 +/- 1.5 g, n = 7 and 13.8 +/- 0.8
      g, n = 24; P greater than .2) and considerably greater for acetylcholine (20.5 +/
      1.3 g, n = 14; P less than .005). The serotonin antagonists ketanserin and
      methysergide reversed completely the effect of fenoldopam (5 x 10(-7) M) with
      IC50 values of 2.5 x 10(-9) and 2.7 x 10(-9) M, respectively. Phentolamine,
      rauwolscine and chlorpheniramine were also effective, but they were less potent
      (IC50 values 6.6 x 10(-8), 1.0 x 10(-7) and 1.7 x 10(-7) M, respectively). By
      contrast, only very high concentrations (IC50, 5.3 x 10(-5) M) of terazosin
      produced an inhibition of fenoldopam-induced tension increases. The effect of
      antagonists could be overcome by increasing the fenoldopam concentration.
      Experiments performed on strips precontracted with serotonin (5 x 10(-8) M)
      revealed a very similar order of potency for the five antagonists. The addition
      of serotonin did not increase the tension produced by supramaximal concentrations
      of fenoldopam (and vice-versa), whereas acetylcholine increased tension
      further.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346636
TI  - Complex prejunctional actions of the D2 dopamine agonists N-0923 and N-0924 in
      the rat tail artery.
AB  - In rat tail arteries preloaded with [3H]norepinephrine, the D2 dopamine receptor
      agonist N-0923 [(S)-(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin++
      +], (S)-(-)-enantiomer of N-0437 [2-(N-propyl-N-2-thienylethylamino)-5
      hydroxytetralin], inhibited tritium efflux and contractile responses evoked by
      nerve stimulation, indicating a prejunctional site of action. At higher
      concentrations (greater than or equal to 10(-7) M), N-0923 had additional effects
      which were blocked by the alpha-2 receptor antagonist yohimbine. In the presence
      of yohimbine, inhibition by N-0923 (10(-9) to 10(-6) M) of stimulation-evoked
      contractile responses correlated well with inhibition of tritium efflux, effects
      which were antagonized by sulpiride. The (R)-(+) enantiomer, N-0924 [(R)-(+)-2-(N
      propyl-N-2-thienylethylamino)-5-hydroxytetralin++ +], also inhibited stimulation
      evoked contractile responses (EC50 = 5.0 x 10(-7) M) and tritium efflux (EC50 =
      6.0 x 10(-7) M) in the presence of yohimbine, but with reduced potency compared
      to N-0923 (EC50 = 4.0 x 10(-9) and 4.2 x 10(-9) M, respectively). At high
      concentrations (10(-6) M), both enantiomers also increased basal tritium efflux,
      an effect which coincided with contraction in the case of N-0923. The effect of N
      0923 at the D2 receptor, measured as inhibition of stimulation-evoked contractile
      responses, was greatest when the intensity of stimulation was low (low frequency
      or short train lengths). When extracellular calcium was lowered to 1.0 mM, the
      inhibitory effect of N-0923 was increased whereas elevated calcium (5.0 mM)
      attenuated the action of N-0923.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346637
TI  - Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human
      muscarinic cholinergic receptors expressed in Chinese hamster ovary cells.
AB  - We determined the affinity and selectivity of binding for 24 compounds: nine
      antimuscarinics (including some antiparkinson drugs) and 15 neuroleptics
      (including the atypical compounds clozapine, fluperlapine, melperone, rilapine,
      risperidone, tenilapine, tiosperone and zotepine) at the five human muscarinic
      receptor subtypes expressed in Chinese hamster ovary cells. Equilibrium
      dissociation constants (Kd) were obtained from competitive radioligand binding
      studies with [3H]quinuclidinyl benzilate and membranal preparations of these
      cells. As expected, QNB had the highest affinity of the compounds studied at the
      five receptor subtypes and was not selective (Kd ranged from 0.027-0.088 nM).
      Benztropine had the next highest affinity of the antimuscarinic compounds and
      thioridazine had the highest affinity of the neuroleptics. Among the
      antiparkinson drugs, biperiden was the only one selective for the m1 subtype; and
      among the neuroleptics, the atypical drug clozapine was also selective for the m1
      subtype. This selectivity may explain clozapine's unusual efficacy in refractory
      schizophrenic patients and its low incidence of extrapyramidal side effects.
      However, because most other atypical neuroleptics studied lacked high affinity
      and selectivity at muscarinic receptor subtypes, it is likely that other
      mechanisms are involved as well.

PMID- 1346638
TI  - Chronic ethanol feeding produces a muscarinic receptor upregulation, but not a
      muscarinic supersensitivity in lower esophageal sphincter muscle.
AB  - Muscarinic acetylcholine receptors (mAChR) are important in esophageal
      physiology, and mAChR alterations may be involved in ethanol-induced esophageal
      dysfunction. We previously demonstrated that acute ethanol decreases lower
      esophageal sphincter pressure (LESP), whereas withdrawal from chronic ethanol
      results in pressure increases which are reversible by acute ethanol. To see if
      this increase in LESP is due to upregulation of mAChR, we evaluated both mAChR
      binding and dose-response curves for bethanechol and atropine-induced changes in
      LESP before and after acute and chronic ethanol exposure. The number of mAChR
      sites (Bmax) in LES (3.4 fmol/mg tissue) was lowered by acute ethanol (1.72, 
      50%); withdrawal from chronic ethanol raised Bmax (5.2, +54%). Acute injection of
      ethanol into cats in withdrawal reversed this increase in mAChR density (3.1, 
      10%). These changes correlated with our earlier data on ethanol-induced changes
      in LESP. However, the dose-response curve for bethanechol-induced pressure
      increases shifted to the right [ED25 (micrograms/kg); control, 8.6; withdrawal,
      21.3], paralleled by an increase in the number of low-affinity agonist binding
      sites. Thus, 1) the withdrawal-associated increase in Bmax (up-regulation) is
      more likely to be a compensatory response to deficits (functional subsensitivity)
      distal to the receptor recognition site than to proximal deficits; 2) the
      increase in Bmax does not cause LESP hyperactivity; and 3) receptor binding
      changes do not necessarily translate into physiological changes.

PMID- 1346639
TI  - Calcium utilization coupled to stimulation of postjunctional alpha-1 and alpha-2
      adrenoceptors in isolated human resistance arteries.
AB  - Human s.c. resistance arteries (internal diameters 158-353 microns) were mounted
      in a microvascular myograph, and experiments were designed to examine the calcium
      pools utilized by selective stimulation of alpha-1 and alpha-2 adrenoceptors. In
      a concentration-dependent manner, phenylephrine and B-HT 933 evoked contractions
      mediated by alpha-1 and alpha-2 adrenoceptors, respectively, both in calcium
      containing and in calcium-free saline. With respect to the maximum response to
      potassium in calcium-containing saline, the maximum responses to phenylephrine
      and B-HT 933 were 96 +/- 6 and 85 +/- 8%, respectively, in calcium-containing
      saline, and 79 +/- 4 and 14 +/- 2%, respectively, in calcium-free saline. A
      qualitatively similar difference in maximum responses to alpha-1 vs. alpha-2
      adrenoceptor stimulation in calcium-free saline was demonstrated for
      norepinephrine in the presence of antagonists selective for the two alpha
      adrenoceptor subtypes. The maximum relaxation in calcium-containing saline
      produced by the calcium antagonist nitrendipine was 52 +/- 3% in vessels
      precontracted with phenylephrine, but 80 +/- 5% in vessels precontracted with B
      HT 933. A quantitative difference in receptor reserves was demonstrated between
      alpha-1 and alpha-2 adrenoceptors; 90% of the maximum response was obtained at 34
      +/- 5 and 57 +/- 8% receptor occupation, respectively. These data suggest that
      compared to responses mediated by stimulation of postjunctional alpha-1
      adrenoceptors, stimulation of postjunctional alpha-2 adrenoceptors relies heavily
      on calcium influx. Stimulation of postjunctional alpha-2 adrenoceptors is,
      however, also coupled to intracellular release of calcium in isolated human s.c.
      resistance arteries.

PMID- 1346640
TI  - Neuromodulatory effects of atrial natriuretic peptides correlate with an
      inhibition of adenylate cyclase but not an activation of guanylate cyclase.
AB  - We reported previously that atrial natriuretic factor (ANF) and the ANF clearance
      receptor binding peptide, C-ANF(4-23)-NH2 (C-ANF), inhibit catecholamine (CA)
      release from rat, nerve growth factor-treated pheochromocytoma cells (PC12 cells)
      by a guanylate cyclase independent mechanism. This mechanism is most likely a
      pertussis toxin (PTX)-sensitive inhibition of adenylate cyclase. This study
      examines the role of the second messengers, cyclic AMP (cAMP) and cyclic GMP
      (cGMP), in mediating atrial natriuretic factor effects on depolarization-induced
      CA release from PC12 cells. The following evidence supports the hypothesis that
      the neuromodulatory action of atrial peptides is independent of increases in
      cGMP: 1) ANF does not potentiate the inhibitory effect of C-ANF on CA release or
      cAMP generation but still elevates cGMP concentrations in the presence of C-ANF;
      2) the neuromodulatory effects of ANF and C-ANF are blocked or reversed by a
      membrane permeable analog of cAMP, dibutyryl cAMP; 3) ANF and C-ANF attenuate CA
      release in the presence of a maximally effective concentration of dibutyryl cGMP;
      4) the inhibitory effect of dibutyryl cGMP is PTX-insensitive whereas the atrial
      peptide effect is blocked by PTX-pretreatment; and 5) dibutyryl cGMP is without
      effect on adenylate cyclase. These data are consistent with the hypothesis that
      ANF and C-ANF act via the ANF clearance (R2) receptor to suppress adenylate
      cyclase activity and neurotransmission.

PMID- 1346641
TI  - Subtype-selective alpha-1 adrenoceptor alkylation in the rat kidney and its
      effect on the vascular pressor response.
AB  - Separate genes for alpha-1A and alpha-1B adrenoceptors have now been identified.
      Whereas alpha-1 adrenoceptors are known to mediate rat renal vasoconstriction,
      the relative importance of these alpha-1 adrenoceptor subtypes was unknown. We
      cannulated the right suprarenal artery of anesthetized male Sprague-Dawley rats
      to permit administration of the alpha-1A and alpha-1B alkylating antagonists, SZL
      49 (SZL) and chloroethylclonidine (CEC), respectively, directly into the right
      kidney. Treated kidneys were homogenized to identify the doses of SZL and CEC
      that caused the maximum reductions in Bmax for [3H]prazosin, the relatively
      nonselective alpha-1 adrenoceptor antagonist. In other rats, a Doppler flow probe
      was placed around the right renal artery, and dose-peak response curves for
      boluses of the alpha-1 adrenoceptor agonist phenylephrine (PHE) were generated
      before and after supramaximal dosages of SZL or CEC. Renal vasoconstriction to
      PHE was nearly obliterated by SZL. In contrast, CEC caused only a modest
      rightward shift in the PHE DRC. SZL also abolished the renal vascular response to
      two other alpha-1 adrenoceptor agonists, cirazoline and methoxamine. Our data
      support the conclusion that the alpha-1 adrenoceptors at the level of the rat
      renal resistance vessels are predominantly alpha-1A adrenoceptors.

PMID- 1346642
TI  - Influence of age on control of norepinephrine release from the rat tail artery.
AB  - Stimulation-evoked norepinephrine release from the rat tail artery increases with
      age; therefore, the sensitivity of prejunctional alpha-2 adrenergic receptors to
      antagonists and agonists was compared in perfused tail arteries from Fischer-344
      rats, aged 6 and 20 months. The increase in endogenous fractional norepinephrine
      release produced by blockade of alpha-2 adrenergic receptors with submaximal
      concentrations of either yohimbine or idazoxan was significantly greater in 6
      month-old animals as compared to 20 months; however, the effect of a maximal
      concentration of idazoxan was not significantly different. Inhibition of
      norepinephrine release by the alpha-2 receptor agonist UK14304 was reduced in 20
      month-old animals compared to 6 months. In contrast, there were no age-related
      differences in inhibition of contractile responses to nerve stimulation by the
      prejunctionally acting dopamine D2 agonist, N-0923. These data suggest that age
      related changes in the sensitivity of prejunctional alpha-2 receptors to agonists
      and antagonists may not reflect any fundamental alteration in the function of
      this receptor system, but may be related to competition between alpha-2 agonists
      or antagonists and increased biophase concentrations of norepinephrine. This
      conclusion is supported by lack of an age-related change in function of
      prejunctional dopamine D2 receptors. Persistence of age-related increases in
      norepinephrine release when alpha-2 adrenergic receptors are fully blocked may
      reflect an alteration in other fundamental mechanisms that control norepinephrine
      release.

PMID- 1346643
TI  - Release of endogenous noradrenaline from the vascularly perfused rat stomach in
      vitro: modulation by pre- and postsynaptic adrenoceptors.
AB  - We developed an experimental in vitro model to detect a very small amount of
      endogenous noradrenaline (NA) released from the rat gastric sympathetic nerve
      terminals. The stomach was perfused via celiac artery with modified Krebs-Ringer
      solution containing 10 mM pargyline and 0.1% bovine serum albumin at a constant
      flow of 4 ml/min. The right greater splanchnic (SPL) nerve (preganglionic nerve
      of the gastric sympathetic nerve) was stimulated electrically with square-wave
      pulses of 2 msec duration and supramaximal intensity (5 mA) for 1 min. The rat
      stomach contained about 750 ng of NA and spontaneous overflow was about 0.05% of
      tissue content per 2 min. The NA overflow induced by SPL nerve stimulation at 5
      Hz was abolished by tetrodotoxin (3 x 10(-7) M) and by Ca(++)-free medium
      containing 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid.
      Hexamethonium (5 x 10(-4) M) significantly decreased the NA overflow induced by
      SPL nerve stimulation at 5 Hz. Yohimbine (10(-7) and 10(-6) M) and prazosin (10(
      7) and 10(-6) M) dose-dependently enhanced the NA overflow induced by SPL nerve
      stimulation at 5 Hz. Clonidine (10(-7) and 10(-6) M) and methoxamine (10(-5) M)
      significantly decreased the NA overflow induced by SPL nerve stimulation at 1 Hz
      and this methoxamine-induced inhibition was abolished by 8-(p-sulfophenyl)
      theophylline (5 x 10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346644
TI  - Prolonged exposure to catecholamines enhances sensitivity of smooth muscle
      relaxation induced by sodium nitroprusside and atriopeptin.
AB  - Desensitization of alpha-1 adrenergic receptor-mediated contraction occurs in
      aortic smooth muscle from rats after in vitro exposure to norepinephrine (NE).
      The purpose of this study was to examine effects of pretreatment of blood vessels
      with catecholamines on relaxant responses of the vessels to sodium nitroprusside
      (SNP) and atriopeptin III (ANF). Vessels preincubated with NE for 4 hr had a
      markedly increased sensitivity to relaxation induced by SNP as compared to
      controls. The concentration of SNP giving half-maximal relaxation (log EC50) was 
      8.78 +/- 0.09 in the vessels pretreated with NE and -7.40 +/- 0.18 in controls (P
      less than .001). NE-treated vessels also had an increased sensitivity to ANF
      (EC50 -8.23 +/- 0.11 vs. -7.03 +/- 0.31, respectively; P less than .01). However,
      both desensitized and control vessels had similar sensitivity to relaxation
      induced by 8-bromo-cyclic GMP. The capacity of SNP to stimulate intracellular
      cyclic GMP accumulation in vessels pretreated with NE was greater than controls
      at a high concentration of SNP (10(-5) M.). However, there was no correlation
      between vasodilation induced by lower concentrations of SNP and stimulation of
      cyclic GMP accumulation in these blood vessels. Activity of soluble and
      particulate guanylate cyclase in NE-treated vessels was increased compared to
      controls. Changes in sensitivity of smooth muscle relaxation to SNP and ANF after
      prolonged exposure to catecholamines may relate to changes in capacity of the
      cyclic GMP system.

PMID- 1346645
TI  - Suppression by spinal alpha-2 agonists of motor and autonomic responses evoked by
      low- and high-intensity thermal stimuli.
AB  - In halothane (0.9%)-anesthetized rats, the immersion of the tail in 52.5 degrees
      C or 60 degrees C water for 15 sec resulted in a short-latencied tail jerk and a
      subsequent tachycardia and elevation in blood pressure. The i.t. administration
      of the alpha-2 agonists, dexmedetomidine (DMET), clonidine (CLON) and ST-91,
      resulted in a dose-dependent increase in the somatomotor reflex latency and a
      reduction in the magnitude of the increase in the magnitude of the cardiovascular
      response, with the ordering of activity on all endpoints at all temperatures
      being: DMET greater than CLON greater than or equal to ST-91. Increasing the
      stimulus intensity from 52.5 to 60 degrees C resulted in right shifts in the dose
      response curves for all agents with the magnitude of shift being: 1) greatest on
      the blood pressure and least on the tail flick, and 2) greatest for ST-91 and
      CLON and least for DMET. Thus, the dose ratio (ED50 at 60 degrees C/ED50 at 52.5
      degrees C) for these three agents on the tail flick and blood pressure response
      was, respectively, 1.1 and 1.8 for DMET, 1.1 and 4.3 for CLON and 4.8 and 9.7 for
      ST-91 (mean +/- S.E.). On resting blood pressure, i.t. DMET and CLON produced a
      dose-dependent hypotension and bradycardia. ST-91 had no consistent dose
      dependent effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346646
TI  - The influence of environmental temperature on the transient effects of
      methamphetamine on dopamine levels and dopamine release in rat striatum.
AB  - When male rats were injected four times (once every 2 hr) with 5 mg/kg
      methamphetamine (METH) at an environmental temperature of 23 degrees C, transient
      changes occurred in the levels of striatal dopamine (DA) and the regulation of
      striatal DA release. Striatal DA levels were minimally affected 1 day after METH
      treatment, but 3 days after METH treatment, striatal DA levels decreased to
      approximately 40% of control. DA levels returned to 70% of control 2 weeks after
      METH. Similarly, striatal tyrosine hydroxylase (TH) activity decreased to
      approximately 50% of control activity 3 days after METH treatment at 23 degrees
      C, but did not differ from controls at 1 or 14 days after METH treatment. No
      changes in striatal DA levels were observed in rats treated with four doses of 5
      mg/kg METH at an environmental temperature of 4 degrees C. Striatal DA levels
      decreased modestly to approximately 70% of controls 3 days after treatment with
      four doses of 10 mg/kg METH at 4 degrees C, but DA levels returned to control
      levels 14 days after METH treatment. Furthermore, striatal TH activity was not
      affected by 10 mg/kg METH at 4 degrees C. Thus, a cold environmental temperature
      (4 degrees C) reduced the effects of METH on striatal DA levels and striatal TH
      activity. Changes in the presynaptic regulation of DA release after either 5
      mg/kg (23 degrees C) or 10 mg/kg (4 degrees C) METH treatment were determined in
      vitro using striatal slices.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346647
TI  - Pharmacological profile of HS-142-1, a novel nonpeptide atrial natriuretic
      peptide antagonist of microbial origin. I. Selective inhibition of the actions of
      natriuretic peptides in anesthetized rats.
AB  - HS-142-1, a novel polysaccharide, isolated from the culture broth of
      Aureobasidium pullulans var. melanigenum, has been found to inhibit selectively
      the binding of [125I]atrial natriuretic peptide (ANP) to the guanylyl cyclase
      linked ANP receptor (ANP-B receptor) and production of cyclic GMP by ANP. The
      effect of this compound on renal and vascular actions evoked by exogenously
      administered natriuretic peptides was examined in anesthetized rats. The increase
      in urine flow and in the urinary excretion of sodium elicited by human ANP or
      porcine brain natriuretic peptide was prevented by pretreatment with HS-142-1.
      The prevention was accompanied by the inhibition of increase in urinary cyclic
      GMP excretion. In addition, these renal responses were rapidly reversed by an
      injection of HS-142-1 during ANP infusion. Higher doses of HS-142-1 did not alter
      the increase in urine flow and in the urinary excretion of sodium evoked by
      furosemide, and HS-142-1 alone showed no significant change in these renal
      parameters. Hypotensive action elicited by human ANP was also prevented by the
      pretreatment with HS-142-1 and rapidly reversed by treatment with HS-142-1 during
      ANP infusion. These results clearly demonstrate that HS-142-1 acts as an
      antagonist for ANP-B receptor in vivo. HS-142-1, then, provides a new tool for
      the study of the physiological and pathophysiological roles of ANP.

PMID- 1346648
TI  - Differential coupling of somatostatin1 receptors to adenylyl cyclase in the rat
      striatum vs. the pituitary and other regions of the rat brain.
AB  - Subtypes of somatostatin (SRIF) receptors are expressed in the rat brain and may
      mediate the diverse actions of SRIF. In the present study we show that subtypes
      of SRIF receptors in different regions of the rat brain are differentially
      sensitive to the cyclic hexapeptide SRIF analog, MK 678. SRIF1 receptors are
      sensitive to MK 678 and found in high density in the cortex, hippocampus and
      striatum, as well as in the anterior pituitary. The pituitary appears to express
      only the SRIF1 receptor. The cortex, hippocampus and striatum also express SRIF2,
      or MK 678-insensitive, receptors. The proportion of SRIF1 receptors varies in
      different brain regions. In the cortex and hippocampus, SRIF1 receptors comprise
      approximately 50% of the total SRIF receptor population, whereas in the striatum
      SRIF1 receptors comprise the majority (86%) of SRIF receptors. SRIF1 receptors in
      the pituitary, cortex and hippocampus mediate, at least in part, the ability of
      SRIF to inhibit forskolin-stimulated adenylyl cyclase activity as MK 678 produced
      significant inhibition of activity in these tissues. However, in the striatum, MK
      678 had no significant effect on forskolin-stimulated adenylyl cyclase activity,
      despite a significant inhibition produced by SRIF. The specific labeling of these
      receptors in the striatum by [125I]MK 678 is abolished in the presence of high
      concentrations of the nonhydrolyzable GTP analog, GTP gamma S, suggesting that
      SRIF1 receptors in this brain region are coupled to G proteins. The SRIF1
      receptors in the striatum may be coupled via G proteins to cellular transducing
      systems other than adenylyl cyclase.

PMID- 1346649
TI  - Prostaglandin synthesis elicited by adrenergic stimuli is mediated via alpha-2C
      and alpha-1A adrenergic receptors in cultured smooth muscle cells of rabbit
      aorta.
AB  - This study was performed to characterize the subtype of adrenergic receptor(s)
      (AR) involved in prostacyclin synthesis [measured as 6-keto-prostaglandin (PG)F1
      alpha] elicited by AR agonists in cultured vascular smooth muscle cells of rabbit
      aorta. Both alpha-1 and alpha-2 AR agonists enhanced 6-keto-PGF1 alpha synthesis
      in a dose-dependent manner with the following order of potency: norepinephrine
      greater than BHT 933 greater than UK 14304 greater than xylazine greater than
      phenylephrine greater than or equal to methoxamine greater than cirazoline.
      Isoproterenol and oxymetazoline did not alter 6-keto-PGF1 alpha synthesis.
      Methoxamine-induced 6-keto-PGF1 alpha synthesis was not reduced by the alpha-2 AR
      antagonist rauwolscine. The affinities of AR antagonists (PA2 value) in
      inhibiting methoxamine-induced 6-keto-PGF1 alpha synthesis were of the following
      order: prazosin greater than WB 4101 greater than corynanthine greater than
      yohimbine. Administration of WB 4101 and the irreversible alpha-1B AR antagonist
      chloroethylclonidine reduced norepinephrine (in the presence of rauwolscine, 10(
      8) M)- or methoxamine-induced 6-keto-PGF1 alpha synthesis; WB 4101 was more
      potent than chloroethylclonidine. UK 14304-induced 6-keto-PGF1 alpha synthesis
      was not reduced by chloroethylclonidine or BRL 44408, a selective alpha-2A AR
      antagonist, but it was inhibited by other alpha AR antagonists. The affinities of
      AR antagonists (PA2 values) in inhibiting UK 14304-induced 6-keto-PGF1 alpha
      synthesis were of the following order: rauwolscine greater than yohimbine greater
      than BAM 1303 greater than BRL 41992 greater than WB 4101 greater than ARC 239
      greater than or equal to prazosin greater than SKF 104078 greater than or equal
      to corynanthine. The order of affinity of alpha-2 AR antagonists in inhibiting UK
      14304-induced 6-keto-PGF1 alpha synthesis in vascular smooth muscle cells was
      similar to that derived from radioligand binding studies in opossum kidney cell
      line receptors classified as alpha-2C receptors. These data suggest that 6-keto
      PGF1 alpha synthesis elicited by adrenergic stimuli in cultured vascular smooth
      muscle cells of rabbit aorta is mediated primarily via alpha-2C and to a lesser
      extent alpha-1A receptors.

PMID- 1346650
TI  - Neuroprotective effects of the N-methyl-D-aspartate receptor antagonists
      ifenprodil and SL-82,0715 on hippocampal cells in culture.
AB  - The N-methyl-D-aspartate (NMDA) antagonists ifenprodil and SL-82,0715 were
      examined for neuroprotective efficacy against glutamate toxicity of hippocampal
      neurons in culture. Hippocampal cells were grown on 96-well culture plates for 2
      to 3 weeks and then exposed for a 15-min period to glutamate or NMDA.
      Neurodegeneration was quantified 24 hr after the excitotoxin exposure, by
      measuring the activity of lactate dehydrogenase leaked into the culture medium by
      the damaged cells. Glutamate induced a concentration-dependent increase in
      lactate dehydrogenase that reached 3-fold the activity of control cultures. The
      NMDA antagonists MK-801 and AP-7 blocked this neurotoxicity when added either
      during or after the glutamate exposure. Ifenprodil and SL-82,0715 blocked the
      neurotoxicity only when added during the excitotoxin exposure. Ifenprodil was 3
      times more potent than SL-82,0715 in blocking glutamate or NMDA-induced
      neurotoxicity. Glycine did not reverse the neuroprotective effects of these
      antagonists. The neuroprotective effect of ifenprodil or SL-82,0715 did not
      appear to result from actions at alpha-1 adrenergic or sigma receptor sites
      because the alpha-1 adrenergic antagonist prazosin and the sigma ligands
      haloperidol, 3-(3-hydroxyphenyl)-N-propylpiperidine) and 1,3-di-o-tolylguanidine)
      showed no neuroprotective activity. We conclude that ifenprodil and SL-82,0715
      protect cultured hippocampal neurons from excitotoxic damage by antagonizing NMDA
      receptors.

PMID- 1346651
TI  - Synthesis of halogenated trimetoquinol derivatives and evaluation of their beta
      agonist and thromboxane A2 (TXA2) antagonist activities.
AB  - The 5,8-difluoro (4), 5-iodo (5), 8-iodo (6), and 5-trifluoromethyl (7)
      derivatives of trimetoquinol (TMQ, 1) have been synthesized and evaluated for
      their ability to stimulate beta 1 (guinea pig atria) and beta 2 (guinea pig
      trachea) adrenoceptors as well as for their inhibitory activity against U46619 [a
      thromboxane A2 (TXA2) mimetic]-mediated contraction of rat thoracic aorta and
      human platelet aggregation. Both 5 and 6 were considerably less active than TMQ
      on both beta-adrenergic systems and gave a rank order of stimulatory potency of 1
      much greater than 6 greater than or equal to 5. Similarly, iodine substitution at
      either position also caused a reduction in TXA2 antagonist activity with a rank
      order potency of 1 greater than 6 much greater than 5. Compared to 1, however, 5
      iodo-TMQ (5) showed a marked selectivity for blockade of U46619 responses in rat
      aorta over human platelets. On beta-systems, 4 had reduced potency compared to
      TMQ and was similarly nonselective. Introduction of a trifluoromethyl group at
      the 5-position of TMQ completely abolished both beta 1- and beta 2-adrenergic
      agonist activities while imparting weak antagonist activity on beta 1 receptors.
      On TXA2 systems, both 4 and 7 possessed significantly decreased inhibitory
      activity compared to TMQ. The synthetic approaches to the synthesis of 8
      (trifluoromethyl)-TMQ (8) are also described. The enantiomers of the 8-fluoro
      derivative (3) of TMQ were separated on a preparative Chiralcel OD column and
      evaluated on beta-adrenergic systems and TXA2 systems. On beta-adrenergic
      systems, (S)-(+)-8-fluoro-TMQ was at least 10-fold more potent than (R)-(-)-8
      fluoro-TMQ. Conversely, (R)-(-)-8-fluoro-TMQ was approximately 14-fold more
      potent as an antagonist of TXA2-mediated aggregation in human platelets than (S)
      (+)-8-fluoro-TMQ. In contrast to platelets, (S)-(+)-8-fluoro-TMQ was an agonist
      in rat aorta whereas (R)-(-)-8-fluoro-TMQ was an antagonist.

PMID- 1346652
TI  - Centrally acting alpha 1-adrenoceptor agonists based on hexahydronaphth[2,3-b]
      1,4-oxazines and octahydrobenzo[g]quinolines.
AB  - Centrally acting alpha 1-agonists may be of therapeutic value in dementias and
      other CNS disorders characterized by symptoms of noradrenergic insufficiency.
      Therefore, on the basis of known peripherally acting alpha 1-agonists two new
      groups of centrally acting alpha 1-agonists with improved lipophilicity, the
      hexahydronaphth[2,3-b]-1,4-oxazines type A and the octahydrobenzo[g]quinolines
      type B were designed. The N-methylated derivatives 14 and 33 demonstrate potent,
      direct agonistic activity at postjunctional alpha 1-receptors. Ring substituent
      alterations in compounds of type A and B change the potency of compounds on the
      rabbit ear artery by over 3 orders of magnitude (pD2 = 5.35-8.40). The efficacy
      of these compounds varies from 42 to 110%. Those alpha 1-agonists which were
      selective in the pithed rat increase vigilance in rats. Compound 14 was found to
      be a centrally acting alpha 1-agonist with good tolerability in different animal
      species and in healthy volunteers. Furthermore, 14 selectively stimulates the
      breakdown of phosphatidylinositol in rat cerebral cortex slices. In vivo, the
      compound reverses behavioral deficits in animals which received noradrenergic
      lesions following DDC or DPS4 treatment. Oxazine 14 and its close derivatives are
      by far more lipophilic than commonly known alpha 1-agonists. This is demonstrated
      in a ClogP-PROBIS plot.

PMID- 1346653
TI  - Pyrrole mannich bases as potential antipsychotic agents.
AB  - Recently, we reported on a series of arylpiperazines 4 which exhibit high
      affinity for the serotonin 5-HT-1A and 5-HT-1B binding sites. Although these
      compounds interact weakly with dopamine D-1 and D-2 receptors, they are
      reasonably potent in inhibiting conditioned avoidance responding (CAR) in the
      rat, an indication of potential antipsychotic activity. Conversion of these
      arylpiperazines to pyrrole Mannich bases has provided a series of compounds (10
      44) which exhibit potent inhibition of CAR when given po and have strong affinity
      for both the D-2 and 5-HT-1A binding sites. Some of these agents also fail to
      produce catalepsy. The D-2 binding data and the block of CAR suggest that they
      are potential antipsychotic agents and the lack of cataleptogenic potential
      suggests some might possess less liability for producing extrapyramidal side
      effects and tardive dyskinesias in man.

PMID- 1346654
TI  - Progress and prospects for human cancer vaccines.

PMID- 1346655
TI  - Hepatic cytolytic and cholestatic changes related to a change of lipid emulsions
      in four long-term parenteral nutrition patients with short bowel.
AB  - Long-term parenteral nutrition hepatic-related impairment is commonly reported
      and diversely explained. However, with a low cyclic caloric intake (100% to 130%
      of basal metabolism calculated with the Harris-Benedict formula) consisting of
      two-thirds glucose, one-third lipid, and 0.20 to 0.25 g of nitrogen per kilogram
      per day, these complications were infrequent in a clinical practice of home long
      term parenteral nutrition. Retrospectively, it was noticed that the switch from
      Intralipid 20% to Ivelip 20% at the same amount was followed within 2 months by
      four cases of jaundice in a population of four home long-term parenteral
      nutrition patients with short bowel disease. Hepatic disturbances were
      characterized by cytolysis and cholestasis and were reversible after switching
      from Ivelip 20% back to Intralipid 20%. Neither viral, nor biliary, nor septic
      etiologies were detected. The exact pathological mechanism remains unknown. The
      basal composition of both lipid emulsions seems to be identical: soy oil emulsion
      emulsified by egg phospholipids. However, some differences exist such as the size
      of particles, the presence of sodium oleate in Ivelip 20%, and the purification
      process of lecithin. These may explain the difference in hepatic tolerance during
      long-term parenteral nutrition.

PMID- 1346656
TI  - Comparison of enteral nutrition and drug treatment in active Crohn's disease:
      results of the European Cooperative Crohn's Disease Study IV.

PMID- 1346657
TI  - Transcutaneous ultrasound measurement of blood-flow in internal mammary artery to
      coronary artery grafts.
AB  - Transcutaneous doppler ultrasound was used to examine internal-mammary-artery
      (IMA) blood-flow in 26 patients with IMA coronary bypass grafts. The ungrafted
      right IMA could be seen in all of 19 patients, the grafted left IMA in 16 of 26,
      and the grafted right IMA in 3 of 7. The velocity profile recorded from the
      proximal part of the grafted IMA is distinct from that of an ungrafted artery,
      with a systolic peak which reflects graft capacitance in the face of high
      intramyocardial resistance, and a diastolic peak which represents graft
      conductance when intramyocardial resistance is low. Total graft blood-flow can be
      estimated from the mean velocity and the measured vessel diameter; resting flows
      ranged from 22 to 79 ml/min. In recently grafted patients, resting graft blood
      flow correlated with myocardial "run-off" estimated from preoperative
      arteriograms; graft blood-flow increased appropriately with exercise. This
      simple, non-invasive technique to measure IMA graft blood-flow may find
      applications for routine postoperative follow-up of patients with IMA grafts and
      for studies on the physiology and pharmacology of coronary artery blood-flow.

PMID- 1346658
TI  - High endothelin-1 immunoreactivity in Crohn's disease and ulcerative colitis.
AB  - Both immunological hypersensitivity and vascular abnormalities have been
      implicated in the pathogenesis of inflammatory bowel disease. In an attempt to
      link the two hypotheses, we sought evidence of local production of endothelin-1,
      a potent vasoconstrictor, in patients with Crohn's disease and ulcerative
      colitis. An immunohistochemical method was used to detect endothelin-1 in tissue
      samples from sixteen Crohn's disease patients, nine ulcerative colitis patients,
      and thirteen controls. In the controls, positively staining cells were infrequent
      in both lamina propria (mean 0.9% of total cells, 95% confidence interval 0.1
      1.7%) and submucosa (2.3%, 0.4-4.1%). The percentage of endothelin-immunoreactive
      cells was significantly higher in the two disease groups than in the controls.
      Among the Crohn's disease patients, there were more immunoreactive cells in the
      submucosa than in the lamina propria (19.1%, 15.2-22.1% vs 12.3%, 8.1-16.5%; p
      less than 0.001), whereas the converse was true for the ulcerative colitis group
      (8.6%, 1.1-16.1% vs 24.4%, 14.1-34.6%; p less than 0.001). Immunoreactive
      macrophage aggregates around submucosal blood vessels were common in samples from
      Crohn's disease patients. Endothelin concentrations, measured by
      radioimmunoassay, in supernatants of homogenised tissue samples were
      significantly higher in Crohn's disease and ulcerative colitis than in controls.
      We suggest that local endothelin production by inflammatory cells may contribute
      to vasculitis in chronic inflammatory bowel disease by inducing intestinal
      ischaemia through vasoconstriction.

PMID- 1346659
TI  - Excessive chromium intake in children receiving total parenteral nutrition.
AB  - Various expert bodies have recommended that the daily parental intake of chromium
      in children receiving total parenteral nutrition (TPN) should be 0.20
      micrograms/kg. To test whether this recommendation is appropriate, we assessed
      chromium intake, serum chromium concentrations, and renal function in 15 children
      receiving TPN. The median duration of TPN use was 9.5 (range 1.3-14) years. The
      children's glomerular filtration rate (GFR), measured by plasma clearance of
      indium-111-DTPA was lower than that of non-TPN controls (70 [SD 17] vs 110 [10]
      ml/min per 1.73 m2). The daily chromium intake averaged 0.15 (0.09) micrograms/kg
      daily but the serum chromium concentration was 20 (4 to 42) times higher than
      that of the controls (2.1 [1.2] vs 0.10 [0.03] micrograms/l; p less than 0.0001).
      GFR was significantly inversely correlated with serum chromium concentration (r =
      -0.60, p less than 0.02), daily chromium intake (r = -0.69, p less than 0.01),
      cumulative parenteral chromium intake (r = -0.72, p less than 0.01), and TPN
      duration (r = -0.52, p less than 0.05). We discontinued chromium supplementation
      of TPN solutions and reassessed the children a year later. Contaminating chromium
      concentrations were 1.0-1.8 micrograms/l in TPN solutions and 0.9 micrograms/l in
      fat emulsions. Drinking water contained 4.3-5.7 micrograms/l. Thus, the chromium
      intake without supplementation was only 0.05 (0.01) micrograms/kg daily. The mean
      serum chromium concentration fell to 0.50 (0.30) micrograms/l but was still
      significantly higher than that in the controls (p less than 0.01). The GFR did
      not change significantly (65 [14] ml/min per 1.73 m2). No patient has shown signs
      of chromium deficiency. Although our patients were receiving less than the
      recommended chromium intake during supplementation, their high serum
      concentrations suggested excessive intake. The recommended parenteral chromium
      intake for children should be lowered.

PMID- 1346660
TI  - Hypernatraemia surveillance during a national diarrhoeal diseases control project
      in Egypt.
AB  - The nationwide introduction of oral rehydration therapy to Egypt has led to
      improvement in diarrhoea case management and a fall in infant and child
      mortality. With the wider use of oral rehydration solution (ORS) prepared from
      packets, the incidence of hypernatraemia (serum sodium greater than 150 mmol/l)
      in inpatients with dehydration seen at Abu El-Reeche Hospital, Cairo, increased
      between 1980 and 1984. Systematic surveillance of hypernatraemia in the
      outpatient rehydration unit began in late 1984, and we report trends in
      hypernatraemia and analyses of key variables affecting its incidence in
      dehydrated children. In 1980, 17 of 100 children sampled had hypernatraemia and 2
      had severe hypernatraemia (ie, serum sodium greater than 165 mmol/l). The
      frequency in inpatients peaked at 49% of 222 children in 1984 (19% with severe
      hypernatraemia). Between 1986 and 1989, at least 1000 dehydrated outpatients were
      surveyed each year; by 1989 the incidence of hypernatraemia had fallen to around
      10% (2% severe hypernatraemia). The rise and decline coincided with increasing
      use of ORS and then increasing ability of mothers to mix the solution correctly.
      Hypernatraemia was positively related to the quantity of ORS taken, severity of
      dehydration, nutritional status, and the cooler season, and negatively related to
      age and duration of diarrhoea. Explanations for our findings include improved use
      of ORS and better case-management. Good practice promoted through the mass media
      has facilitated these changes; if the standard of ORS use is not maintained,
      there may be a case for reducing the sodium content of ORS.

PMID- 1346662
TI  - Paroxysmal nocturnal haemoglobinuria.

PMID- 1346661
TI  - Strong association of insulin autoimmune syndrome with HLA-DR4.
AB  - Insulin autoimmune syndrome is characterised by spontaneous hypoglycaemia without
      evidence of exogenous insulin administration, a high serum concentration of total
      immunoreactive insulin, and the presence of insulin autoantibodies in high titre.
      HLA typing of 27 patients with insulin autoimmune syndrome showed that all had
      DR4, which was present in only 43% of 51 healthy controls (odds ratio 72.1, p
      less than 2 x 10(-6), and 19 (70%) of the patients were positive for the allelic
      combination, Cw4, Bw62, and DR4. Analysis of the nucleotide sequences of the
      DRB1, DQA1, and DQB1 genes showed that all the patients had DRB1*0406, DQA1*0301,
      and DQB1*0302, compared with only 14% of the controls (odds ratio 281, p less
      than 1 x 10(-10). We conclude that the development of insulin autoimmune syndrome
      is associated with a strong genetic predisposition.

PMID- 1346663
TI  - Indoor air pollution and acute respiratory infections in children.

PMID- 1346664
TI  - Vesicoureteric reflux and nephropathy.

PMID- 1346665
TI  - Ethical emergencies.

PMID- 1346666
TI  - Clinical examination in diagnosis and subclassification of stroke.

PMID- 1346667
TI  - Clinical diagnosis of transient ischaemic attacks.

PMID- 1346668
TI  - Failure of chloramphenicol therapy in penicillin-resistant pneumococcal
      meningitis.
AB  - First-line therapy for meningitis is often penicillin plus chloramphenicol.
      Penicillin-resistant Streptococcus pneumoniae (PRSP) infections are increasing
      world wide, but the efficacy of chloramphenicol for PRSP meningitis is unknown.
      We therefore prospectively assessed children with pneumococcal meningitis treated
      with penicillin plus chloramphenicol over 27 months to compare outcome of
      penicillin-susceptible S pneumoniae (PSSP) meningitis with that of PRSP
      meningitis. 68 children with pneumococcal meningitis who survived 24 hours were
      evaluated, of whom 25 had chloramphenicol-susceptible PRSP meningitis that was
      treated initially with chloramphenicol. 20 (80%) of these 25 children had an
      unsatisfactory outcome (death, serious neurological deficit, or poor clinical
      response). By contrast, 14 (33%) of 43 children with PSSP meningitis (treated
      with benzylpenicillin) had an adverse outcome (p less than 0.001). Despite
      similar zone sizes on antibiotic disc testing (indicating chloramphenicol
      susceptibility) the chloramphenicol minimum bactericidal concentrations (MBCs) of
      PRSP isolates were significantly higher than those of PSSP isolates. The higher
      chloramphenicol MBCs resulted in borderline cerebrospinal-fluid bactericidal
      activity in many cases of PRSP meningitis and frequent treatment failure. Current
      definitions of chloramphenicol susceptibility of S pneumoniae may be
      inappropriate for management of pneumococcal meningitis. We suggest that
      chloramphenicol should not be used for the management of PRSP meningitis;
      alternative agents, such as third-generation cephalosporins, are more
      appropriate.

PMID- 1346670
TI  - Breast cancer treatment and natural history: new insights from results of
      screening.

PMID- 1346669
TI  - Outbreak of human rabies in the Peruvian jungle.
AB  - Transmission of rabies to man by vampire bats has been known for 60 years but
      there have been few reports of the features of rabies transmitted in this way.
      These aspects of the disease were investigated during an outbreak in Peru in
      early 1990. Between Jan 1 and April 30, 1990, 29 (5%) of 636 residents of the two
      rural communities in the Amazon Jungle in Peru acquired an illness characterised
      by hydrophobia, fever, and headache and died shortly thereafter. A census in one
      of the two towns revealed that the proportion affected was significantly higher
      for 5-14 year olds (17%) than for other age-groups (p less than 10(-5).
      Interviews conducted with 23 of the patients or their families revealed that 22
      (96%) had a history of bat bite, compared with 66 (22%) of 301 community members
      who remained healthy (p less than 10(-6). A rabies virus strain identical to
      those isolated from vampire bats (Desmodus rotundus) was isolated from the brain
      of the only person on whom necropsy could be done. Because of the extreme
      isolation of this and other communities affected by bat-transmitted rabies,
      preventive measures should be directed at decreasing the risk of nocturnal
      exposure to bats by bat proofing dwellings or use of mosquito nets and at prompt
      wound care. Rabies pre-exposure or postexposure vaccination is clearly indicated,
      but may not be feasible in these isolated populations.

PMID- 1346671
TI  - Australia: compensation for medically acquired AIDS.

PMID- 1346672
TI  - Adjuvant treatment in breast cancer.

PMID- 1346673
TI  - Adjuvant treatment in breast cancer.

PMID- 1346674
TI  - Adjuvant treatment in breast cancer.

PMID- 1346676
TI  - Adjuvant treatment in breast cancer.

PMID- 1346675
TI  - Adjuvant treatment in breast cancer.

PMID- 1346677
TI  - Adjuvant treatment in breast cancer.

PMID- 1346678
TI  - Bone-density measurement.

PMID- 1346679
TI  - Headache recurrence after subcutaneous sumatriptan.

PMID- 1346680
TI  - Manganese intoxication during total parenteral nutrition.

PMID- 1346681
TI  - Stress and Graves' disease.

PMID- 1346682
TI  - Stress and Graves' disease.

PMID- 1346683
TI  - Stress and Graves' disease.

PMID- 1346685
TI  - Stress and Graves' disease.

PMID- 1346684
TI  - Incontinence after stroke.

PMID- 1346686
TI  - Effect of co-trimoxazole on stool recovery of Blastocystis hominis.

PMID- 1346687
TI  - False-positive legionella serology in campylobacter infection.

PMID- 1346688
TI  - Immunofluorescence technique for the identification of polioviruses.

PMID- 1346689
TI  - Co-transplantation of peripheral nerve and adrenal medulla in Parkinson's
      disease. CHP Neural Transplantation Group.

PMID- 1346690
TI  - Cultured human fetal and rat brain tissue and Parkinson's disease.

PMID- 1346691
TI  - Noonan's syndrome and coagulation-factor deficiencies.

PMID- 1346692
TI  - Second chance for the adrenal medulla transplant.

PMID- 1346693
TI  - Age and dialysis.

PMID- 1346695
TI  - Immigrant doctors in Israel.

PMID- 1346694
TI  - Age and dialysis.

PMID- 1346696
TI  - Are there too many medical beds?

PMID- 1346697
TI  - Glutaraldehyde allergy in endoscopy units.

PMID- 1346698
TI  - Research in developing countries.

PMID- 1346699
TI  - Euphorbia species.

PMID- 1346700
TI  - Inhibition of NO synthesis in septic shock.

PMID- 1346701
TI  - Inhibition of NO synthesis in septic shock.

PMID- 1346702
TI  - Dissection of vertebral artery after cervical trauma.

PMID- 1346704
TI  - Pulmonary hypertension and dexfenfluramine.

PMID- 1346703
TI  - Pulmonary hypertension and dexfenfluramine.

PMID- 1346705
TI  - Influence of ethanol on toxicity of paraquat and Amanita phalloides.

PMID- 1346706
TI  - Teratogenicity of misoprostol.

PMID- 1346707
TI  - Azithromycin for cerebral toxoplasmosis.

PMID- 1346708
TI  - 3-Deaza-adenosine and inhibition of HIV.

PMID- 1346709
TI  - Screening for HIV p24 antigen.

PMID- 1346710
TI  - c-erbB-2 amplification and identical p53 mutations in concomitant transitional
      carcinomas of renal pelvis and urinary bladder.

PMID- 1346711
TI  - Litigation over congenital scalp defects.

PMID- 1346712
TI  - Salmonellae from a pet snake and its bedding.

PMID- 1346713
TI  - Enkephalin hydrolysis by mouse plasma in vitro.
AB  - Hydrolysis of [Leu]- and [Met]enkephalin was determined in samples of pooled
      whole mouse plasma in vitro by using HPLC-ECD to measure accumulation of Tyr
      containing metabolites. More Tyr-Gly-Gly accumulated from [Met]enkephalin than
      from [Leu]enkephalin hydrolysis, and [Met]enkephalin's half-life in mouse plasma
      was approximately half that of [Leu]enkephalin. Comparisons of metabolite
      formation in the presence versus the absence of inhibitors with high selectivity
      for various peptidases demonstrated that a bestatin-sensitive aminopeptidase,
      presumably aminopeptidase M, as well as enkephalinase and angiotensin converting
      enzyme, participate in the hydrolysis of enkephalin in mouse plasma.

PMID- 1346714
TI  - Distribution of somatostatin-28 (1-12) in the cat brainstem: an
      immunocytochemical study.
AB  - We studied the distribution of somatostatin-28 (1-12)-immunoreactive fibers and
      cell bodies in the cat brainstem. A moderate density of cell bodies containing
      the peptide was observed in the ventral nucleus of the lateral lemniscus,
      accessory dorsal tegmental nucleus, retrofacial nucleus and in the lateral
      reticular nucleus, whereas a low density of such perikarya was found in the
      interpeduncular nucleus, nucleus incertus, nucleus sagulum, gigantocellular
      tegmental field, nucleus of the trapezoid body, nucleus praepositus hypoglosii,
      lateral and magnocellular tegmental fields, nucleus of the solitary tract,
      nucleus ambiguous and in the nucleus intercalatus. Moreover, a moderate density
      of somatostatin-28 (1-12)-immunoreactive processes was found in the dorsal
      nucleus of the raphe, dorsal tegmental nucleus, accessory dorsal tegmental
      nucleus, periaqueductal gray and in the marginal nucleus of the brachium
      conjunctivum. Finally, few immunoreactive fibers were visualized in the
      interpeduncular nucleus, cuneiform nucleus, locus coeruleus, nucleus incertus,
      superior and inferior central nuclei, nucleus sagulum, ventral nucleus of the
      lateral lemniscus, nucleus praepositus hypoglosii, medial vestibular nucleus,
      Kolliker-Fuse area, nucleus ambiguous, retrofacial nucleus, postpyramidal nucleus
      of the raphe, nucleus of the solitary tract, dorsal motor nucleus of the vagus,
      lateral reticular nucleus and laminar and alaminar spinal trigeminal nuclei.

PMID- 1346715
TI  - Characterization of [125I]Tyr11-somatostatin binding sites in the rabbit retina.
AB  - We have identified specific receptors for somatostatin (SS) in the rabbit retina
      using the radioligand [125I]Tyr11-Somatostatin. [125I]Tyr11-SS bound with high
      affinity to retinal membranes as was ascertained by both kinetic and saturation
      experiments. Scatchard analysis of the saturation data for [125I]Tyr11-SS binding
      to retinal membranes suggest a single population of sites with an apparent
      affinity constant (KD) of 0.90 +/- 0.20 nM and a maximum number of binding sites
      (Bmax) of 104 +/- 52 fmol/mg protein. The specific binding of [125I]Tyr11-SS was
      displaced in a dose-dependent manner by SS, Tyr11-SS, SMS 201-995, SS-28 and D
      Trp8-SS. The inactive SS analog SS28(1-14) as well as the peptides CRF and
      bombesin had no effect. In addition, the specific binding of [125I]Tyr11-SS was
      attenuated by GTPgS. These findings demonstrate the presence of a selective
      receptor for SS in the rabbit retina that is coupled to guanine nucleotide
      binding protein(s).

PMID- 1346716
TI  - Sialyl-Tn, sialyl-Lewis Xi, CA 19-9, CA 125, carcinoembryonic antigen, and tissue
      polypeptide antigen in differentiating ovarian cancer from benign tumors.
AB  - Serum sialyl-Tn, sialyl-Lewis Xi, CA 19-9, CA 125, carcinoembryonic antigen
      (CEA), and tissue polypeptide antigen were measured in 65 women with early-stage
      ovarian cancer (45 stage I and 20 stage II cases) and 317 with benign pelvic
      masses. As a single assay, sialyl-Tn showed the best sensitivity and specificity,
      46 and 92%, respectively. CA 19-9 detected the greatest number of cancer patients
      but had the lowest specificity. The combination of sialyl-Tn, CA 125, tissue
      polypeptide antigen, and CEA seemed to perform the best, with a sensitivity and
      specificity of 71 and 76%, respectively. The combination of sialyl-Tn, CA 125,
      and tissue polypeptide antigen gave similar results and may be more cost
      effective. However, one-fifth of the patients with early-stage cancer still
      showed up as false negatives even with use of the six markers in combination.
      Approaches other than serum assay alone will be needed to detect all malignant
      pelvic masses at an early stage.

PMID- 1346717
TI  - Drug update. Drugs for severe pain.

PMID- 1346718
TI  - Role of alpha 1 receptors in the behavioural supersensitivity to D2 agonists
      induced by chronic treatment with imipramine.
AB  - Chronic treatment with imipramine increased the locomotor response to quinpirole,
      a selective D2 receptor agonist. This effect was blocked by minute doses of
      prazosin (0.1-1 mg/kg), a selective alpha 1 receptor blocker, in a dose-dependent
      manner. Conversely, in control rats the locomotor response to quinpirole was
      enhanced by the stimulation of alpha 1 receptors with the selective agonist St
      587. The results suggest that alpha 1 receptor stimulation plays a permissive
      role in the supersensitivity of D2 receptors following chronic treatment with
      imipramine.

PMID- 1346719
TI  - 5-HT1A receptor-effector system responsivity in panic disorder.
AB  - To explore 5-HT1A receptor responsivity in panic disorder (PD), hypothermic,
      neuroendocrine and behavioral responses to the selective partial 5-HT1A receptor
      agonist ipsapirone (IPS) were investigated in patients with primary PD and
      healthy controls. Fourteen patients and matched controls received a single oral
      dose of 0.3 mg/kg IPS or placebo under double-blind, random-assignment
      conditions. IPS induced hypothermia and corticotropin (ACTH)/cortisol release but
      had only minimal effects on behavior. Compared with controls, the patients with
      PD exhibited significantly attenuated thermoregulatory and neuroendocrine
      responses to IPS. Although the healthy subjects reported increased drowsiness and
      the PD patients rated themselves more nervous and less calm following
      administration of IPS, no consistent changes in ratings of anxiety or panic
      symptoms were recorded. The impaired hypothermic and ACTH/cortisol responses
      following 5-HT1A receptor activation reflects subsensitivity of both the pre- and
      post-synaptic 5-HT1A receptor-effector system, thus supporting the hypothesis
      that a 5-HT1A receptor-related serotonergic dysfunction may be linked to the
      pathophysiology of PD. Future studies of 5-HT1A receptor-effector complex
      function in conjunction with assessment of the responsivity of other subtypes
      (e.g. 5-HT2, 5-HT3) should promote the evaluation of 5-HT system integrity in
      anxiety disorders and its involvement in anxiolytic drug effects.

PMID- 1346720
TI  - Early postnatal clonidine treatment results in altered regional catecholamine
      utilisation in adult rat brain.
AB  - Clonidine is a clinically used antihypertensive which has been suggested to
      produce physiological changes in children after exposure in utero. The aim of our
      study was to test the hypothesis that chronic exposure of the developing brain to
      an alpha 2-adrenergic agonist like clonidine would influence the adult
      neurochemical setting of central monoamine neurotransmitter systems. Male rat
      pups were treated from postnatal day 8 to 21 twice daily with saline or with 0.1
      mg/kg clonidine. After the last injection on day 21, brain regional catecholamine
      utilisation was determined using synthesis inhibition with alpha-methyl-p
      tyrosine in a subgroup of the pups. The expected decrease in noradrenaline
      utilisation after clonidine was observed, although statistical significance was
      not reached in a number of brain regions. Dopamine utilisation was not affected.
      The other pups were left to reach young adulthood and catecholamine utilisation
      was measured on day 90. Noradrenaline utilisation on day 90 was significantly
      decreased in two regions: the medulla-pons and the mesolimbic (dopamine
      projection) areas. Dopamine utilisation was decreased in the hypothalamus and
      increased in the amygdala and the cerebellum. These adult neurochemical
      alterations corroborate previous findings of adult behavioural, physiological and
      central biochemical alterations in rats exposed to clonidine in early postnatal
      life.

PMID- 1346722
TI  - Role of D-1 and D-2 receptors in apomorphine-induced pecking in chicks.
AB  - The possible involvement of subtypes of dopamine (DA) receptors in pecking
      induced by apomorphine (APO) in chicks was studied. D-1/D-2 agonist APO dose
      dependently induced pecking in chicks. The APO response was decreased in animals
      pretreated with either the D-2 receptor antagonist sulpiride or the D-1 receptor
      antagonist SCH 23390. The inhibitory effects of both antagonists were also dose
      dependent. The pecking induced by APO was completely inhibited in animals
      pretreated with a combination of SCH 23390 and sulpiride and was potentiated with
      reserpine. Single administration of D-2 agonist quinpirole or D-1 agonist SKF
      38393 did not induced pecking, although quinpirole, but not SKF 38393 caused
      considerable response in reserpine or reserpine + alpha-methyl-p-tyrosine (AMPT)
      treated animals. When quinpirole was administered with SKF 38393, a slight
      pecking response was shown. This was also potentiated in reserpine or reserpine +
      AMPT-treated chicks. The results may indicate that both D-1 and D-2 DA receptors
      are involved in pecking induced by APO, and reserpine treatment caused the
      sensitization of the D-2 receptors for the induction of pecking in chicks.

PMID- 1346721
TI  - Analgesic and discriminative stimulus properties of U-62,066E, the selective
      kappa-opioid receptor agonist, in the rat.
AB  - The analgesic and discriminative stimulus properties of U-62,066E, a selective
      kappa-opioid receptor agonist, were investigated in the rat and compared with
      those of morphine. In the hot-plate test, U-62,066E produced a potent analgesic
      effect almost comparable to that of morphine. U-62,066E-induced analgesia was far
      less sensitive to antagonism by naloxone than was morphine-induced analgesia, but
      was potently reversed by MR-2266, a kappa-receptor antagonist. Although tolerance
      occurred to both U-62,066E and morphine analgesia, there was no cross-tolerance
      between these drugs. U-62,066E did show cross-tolerance to U-50,488H, another
      selective kappa-receptor agonist. Rats were trained to discriminate either 1.0
      mg/kg U-62,066E or 3.2 mg/kg morphine from saline in a two-level food-reinforced
      procedure. The stimulus effect of U-62,066E was substituted for by U-50,488H and
      E-2078 a stable dynorphin derivative, but not by morphine. None of the kappa
      agonists substituted for the morphine stimulus. Although U-62,066E stimulus by
      itself was not antagonized by MR-2266 or naloxone up to as high a dose as 10
      mg/kg, the U-62,066E-like stimulus effect of U-50,488H was markedly blocked by MR
      2266. The dopamine antagonists haloperidol and sulpiride substituted for the U
      62,066E stimulus cue that was, however, not attenuated by the dopamine agonist
      lisuride. Lisuride reversed the U-62,066E-like stimulus induced by U
      50,488H.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346723
TI  - Anxiolytic effect of carbamazepine in the elevated plus-maze: possible role of
      adenosine.
AB  - In order to extend previously reported observations with other animal models of
      anxiety, the effect of carbamazepine (CBZ) was presently measured in rats placed
      on the elevated plus-maze. Intraperitoneal injection of CBZ (5-40 mg/kg)
      increased the percentage of open arm entries as well as the percentage of time
      spent on the open arms of the maze, without affecting the total number of arm
      entries. This effect is characteristic of anxiolytic drugs. The inhibitor of
      adenosine neuronal uptake papaverine (5-40 mg/kg) caused a similar anxiolytic
      effect, whereas the adenosine receptor antagonist aminophylline (1-4 mg/kg)
      selectively decreased the percentage of open arm entries, indicative of an
      anxiogenic effect. Furthermore, the combination of an anxiogenic dose (4 mg/kg)
      of aminophylline with an anxiolytic dose (40 mg/kg) of CBZ resulted in
      cancellation of each other effects. Since reported neurochemical evidence shows
      that CBZ interacts with adenosine receptors, the present results provide
      preliminary support for a participation of this neurotransmitter in the
      anxiolytic action of CBZ.

PMID- 1346725
TI  - Cross cultural communication to help physician assistants provide unbiased health
      care.
AB  - Teaching cross cultural communication typically involves instruction in
      differences between groups. As part of this course in cross cultural
      communication, six specific underserved population groups are introduced to
      students as a cultural experience. Additionally, instruction is provided to
      sensitize students to their personal biases and prejudices through videotaped
      mock interviews. The combination of instruction and experience forms a paradigm
      for teaching cross cultural communication in a way that has personal and
      immediate impact on faculty members and students. The model, "Differences +
      Discomforts = Discoveries," inhibits factionalizing and promotes depth of
      knowledge about underserved groups as well as personal awareness of prejudicial
      feelings. As a result, students learn techniques to provide unbiased health care
      to these, and other, populations.

PMID- 1346724
TI  - Effects of the 5-HT1A partial agonists gepirone, ipsapirone and buspirone on
      local cerebral glucose utilization in the conscious rat.
AB  - The azospirones gepirone (10 mg/kg), ipsapirone (10 mg/kg) and buspirone (10
      mg/kg) were examined for their effect on regional cerebral glucose utilization in
      conscious rats using quantitative 2-deoxy-glucose autoradiography. All three 5
      HT1A partial agonists reduced glucose utilization in the hippocampus and dentate
      gyrus by 20-25% and increased glucose utilization by 38-65% in the lateral
      habenular nucleus; an important relay between striatal/limbic areas and the mid
      brain raphe nuclei. The findings emphasize the potential importance of the
      hippocampus as a site of action for 5-HT1A receptor active drugs in vivo and also
      suggest that functional activity in the striatal/limbic-habenular-raphe pathway
      may be influenced by gepirone, ipsapirone and buspirone.

PMID- 1346726
TI  - Tumour necrosis factor B gene polymorphism in relation to complotype in couples
      with spontaneous abortions and in control families.
AB  - NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis
      factor B (TNFB) gene gives two allelic fragments of 5.5 and 10.5 kb,
      corresponding to the TNFB*1 and TNFB*2 alleles, respectively. The frequencies of
      these alleles were analysed in 121 healthy Finns and 56 Finnish couples suffering
      from recurrent spontaneous abortions (RSA). In the healthy Finns the frequency of
      TNFB*1 was 37% and that of TNFB*2 63%, of which the frequency of TNFB*1 was
      significantly increased compared with the Danish population. No deviation was
      seen between the RSA couples and the Finnish controls. TNF genes are located in
      major histocompatibility complex class III region close to complement (BF, C4A
      and C4B) genes. Some complotypes associated most often with the TNFB*1 (S01, S30,
      S02) and some (S31, F320) with the TNFB*2 allele in the healthy Finns. The
      combination of the TNFB and the C4 'null' allele differed between the RSA couples
      and the Finnish controls.

PMID- 1346727
TI  - In vitro activation of human T lymphocytes by Haemophilus influenzae type b
      capsular polysaccharides.
AB  - Polyribosilribitolphosphate (PRP), the capsular polysaccharide from Haemophilus
      influenzae type b, is a T-cell-independent type 2 antigen. In vitro culture of
      adult peripheral blood T cells with 15 micrograms/ml PRP leads to induction of
      interleukin-2 receptor (IL-2R) expression on up to 10% of T cells. These cells
      are CD4+ and carry the alpha beta T-cell receptor. PRP, at concentrations above 1
      5 micrograms/ml, can also induce in vitro proliferation of both adult and
      neonatal T cells. We conclude that PRP acts as a human T-cell mitogen. The in
      vitro proliferative response as well as IL-2R expression was studied in T cells
      derived from adults after vaccination with native PRP, with PRP conjugated to a
      carrier protein, or with diphtheria toxoid. Vaccination with conjugated PRP
      decreased the doses of PRP required for in vitro induction of IL-2R expression
      and T-cell proliferation. This indicates that vaccination with PRP conjugated to
      a carrier protein improves the in vitro T-cell response to PRP activation.

PMID- 1346728
TI  - Frequency of chicken CD4+ and CD8+ cells. Genetic control and effect of Rous
      sarcoma virus infection.
AB  - In chickens from congenic inbred lines CB and CC that differ only in the major
      histocompatibility complex (MHC), we observed significantly different percentages
      of CD4+ and CD8+ cells in peripheral blood lymphocytes (PBL) and spleen. Positive
      cells were detected by indirect immunofluorescence test as analysed by flow
      cytometry. In both PBL and spleen cell suspensions, the number of CD4+ cells was
      significantly higher in CB than in CC chickens, whereas in CC birds there was a
      higher percentage of CD8+ cells than in CB. These statistically significant
      differences were under the MHC control. We found no statistically significant
      influence of regressions or progression of Rous sarcoma virus-induced tumours on
      the percentage of peripheral T cells and on the interleukin-2 production in
      vitro.

PMID- 1346729
TI  - The influence of prior synaptic activity on the induction of long-term
      potentiation.
AB  - Long-term potentiation (LTP) is an extensively studied model of synaptic
      plasticity, in part because it is a plausible biological correlate for the
      Hebbian synaptic modification that forms the basis for theoretical models of
      neural development, learning, and memory. Although these models must incorporate
      algorithms that constrain synaptic weight changes, physiological evidence for
      such mechanisms is limited. Examination of LTP in area CA1 of the hippocampus
      revealed that the threshold for LTP induction was not fixed but could be strongly
      influenced by the recent history of synaptic activity. This effect was transient,
      synapse-specific, and dependent on postsynaptic N-methyl-D-aspartate (NMDA)
      receptor activation. These results suggest that the threshold for LTP induction
      may be continually adjusted according to the recent history of NMDA receptor
      activation and provide a physiological mechanism by which LTP can be transiently
      inhibited.

PMID- 1346730
TI  - The results of reduced-size liver transplantation, including split livers, in
      patients with end-stage liver disease.
AB  - We initiated a policy of using RSLT in critically ill patients in June of 1988.
      Since that time we have performed 30 RSLTs in 29 patients, including 28 children
      and 1 adult. The mean age of the children was 27 months (range 1 month to 10
      years) with 14 (52%) being 1 year of age or less. The mean weight was 11.3 kg
      (range 2-50 kg) with 20 being 10 kg or less. A total of 22 patients were in the
      intensive care unit at the time of RSLT including 9 who were intubated. Of the 30
      RSLTs, 23 were performed as a primary transplant while 7 were retransplants.
      Indications for primary transplantation included biliary atresia (n = 11),
      fulminant hepatic failure (n = 5), neonatal hepatitis (n = 4) and others (n = 3).
      The RSLT was used in retransplantation for primary nonfunction (n = 2), hepatic
      artery thrombosis (n = 2), chronic rejection (n = 2), and herpetic hepatitis (n =
      1). The size reductions included 18 left lobes, 7 left lateral segments, and 5
      right lobes. This group includes the use of the split-liver technique, which was
      applied to 10 patients (5 livers). The median donor/recipient weight ratio for
      left lobe transplants was 2:1; left lateral segments was 7.3:1; and right lobes
      1.6:1. One year actuarial patient and graft survivals were 68 and 65%,
      respectively, with a mean follow-up of 10.6 months. The number of children dying
      awaiting transplantation has been significantly reduced following the
      introduction of RSLD (3 of 115, 2.6% vs. 12 of 95, 13%; P less than 0.02).

PMID- 1346731
TI  - RS-61443--a phase I clinical trial and pilot rescue study.
AB  - RS-61443, a morpholinoethyl ester of mycophenolic acid, inhibits the synthesis of
      guanosine monophosphate, which plays a pivotal role in lymphocyte metabolism. The
      drug blocks proliferative responses of T and B lymphocytes, and inhibits antibody
      formation and the generation of cytotoxic T cells. In vivo, RS-61443 prolongs the
      survival of islet allografts in mice, heart allografts in rats, and kidney
      allografts in dogs. Reversal of ongoing acute rejection was demonstrated in rat
      heart allografts and kidney allografts in dogs. Preliminary evidence suggests
      that the drug prevents chronic rejection. The purpose of this study was to test
      the safety and tolerance in patients receiving primary cadaver kidneys. RS-61443
      in doses from 100 mg/day p.o. to 3500 mg/day p.o. was given to patients in
      combination with cyclosporine and prednisone. Further study goals were to
      evaluate the pharmacokinetics of RS-61443, watch for the occurrence of
      opportunistic infections and acute rejection, and establish dosages for further
      clinical trials. Forty-eight patients were entered, with six patients in each
      dose group. RS-61443 was well tolerated in all dose groups, with only one adverse
      event possibly related to the drug (hemorrhagic gastritis). There was a
      statistically significant correlation between rejection episodes and dose (P =
      0.022), patients with rejection episodes versus dose (P = 0.038), and number of
      OKT3/prednisone courses versus dose (P = 0.008). There was no overt
      nephrotoxicity or hepatotoxicity. Preliminary results of a rescue trial in 20
      patients with kidney transplants will also be presented.

PMID- 1346732
TI  - Immunohemopoietic effects of dietary nucleotide restriction in mice.
AB  - The influence of dietary sources of nucleotides on host in vivo and in vitro
      immuno-hematologic responses in BALB/c (NCI) mice was studied. Adenosine
      deaminase (ADA) and purine nucleoside phosphorylase (PNP) were measured in
      popliteal lymph nodes undergoing proliferative response to syngeneic and
      allogeneic in vivo stimulation. Supplementation of a nucleotide-free (NF) diet
      with yeast RNA (NFR) or uracil (NFU) significantly enhanced the host PLN immune
      response as compared with NF and NF supplemented with adenine (NFA) diets. Levels
      of ADA and PNP enzymes in the PLNs increased with the alloimmune PLN response of
      host, and immunosuppression was associated with decreased ADA and PNP activities
      in lymphocytes following antigenic stimulation. The induction of these enzymes
      during immune response appears to require dietary sources of certain nucleotides.
      When bone marrow cells from control chow fed animals were cultured with
      supernatants (sups) from mitogen activated splenocytes of animals on each dietary
      group, NF sups significantly decreased (P less than 0.05) the BM proliferative
      response compared with the response observed with NFR sups, and similar to NFA or
      NFU sups. When stimulated with purified IL-3, NFR BM cells had higher levels of
      Thy1.2 or Lyt 1 surface markers as compared with other test groups. In the in
      vivo splenic colony formation-CFUs assay, spleens from NFR- and NFU-fed animals
      had a significantly higher number of colonies than spleens from NF- or NFA-fed
      mice. Thus, NF diet decreases both in vivo lymphoproliferation response to
      alloantigen and hemopoietic growth factor production, rendering the host splenic
      environment deficient for stem cell growth. These adverse effects are reversed by
      RNA supplementation of NF diet. These nutritional studies demonstrate a critical
      and regulatory role for dietary nucleotides in immunohemopoiesis.

PMID- 1346734
TI  - The official AIDS caseload will grow.

PMID- 1346733
TI  - Allograft rejection in CD4+ T cell-reconstituted athymic nude rats--the
      nonessential role of host-derived CD8+ cells.
AB  - PVG-rnu/rnu nude rats reject fully allogenic renal (DA) and skin (BN, AO)
      allografts after the adoptive transfer of naive CD4+ T cells alone, but rejection
      is accompanied by the accumulation of many nude-derived CD8+ leukocytes within
      the graft. In addition, mononuclear cells infiltrating the rejecting renal grafts
      in these animals display cytotoxic activity in vitro against specific and third
      party alloantigens. In this investigation we have treated CD4+ T cell-restored
      nude rats bearing renal or skin allografts with the mAb MRC OX8 to deplete the
      host of CD8+ cells. In vivo treatment with OX8 completely eliminated CD8+ cells
      from rejecting grafts of both kidney and skin, but it did not prevent graft
      rejection, nor did OX8 treatment abolish the cytotoxic effector cells found in
      nude rat spleen or in graft-infiltrating cells (GIC) of rejecting renal
      allografts. The nature of the cytotoxic activity was examined with anti-CD3 mAb
      1F4, which was shown to block conventional CD8+ Tc killing in vitro but did not
      inhibit allogeneic target cell lysis by spleen cells from nude rats. The
      cytotoxic activity found in GIC of rejecting allografts was not inhibited by anti
      CD3 mAb, suggesting that these cytotoxic effector cells were CD3-CD8- and were of
      extrathymic origin. We conclude that non-thymus-derived CD8+ GIC are not
      essential for allograft rejection in CD4+ T cell-restored nude rats.

PMID- 1346735
TI  - Analysis of proliferating hepatocytes using a monoclonal antibody against
      proliferating cell nuclear antigen/cyclin in embedded tissues from various liver
      diseases fixed in formaldehyde.
AB  - The authors studied histochemically the morphologic features of proliferating
      hepatocytes positive for proliferating cell nuclear antigen (PCNA/cyclin) to
      analyze the process of liver regeneration in embedded tissues fixed with
      formaldehyde using an anti-PCNA/cyclin monoclonal antibody. In liver specimens
      from patients with acute viral hepatitis (AVH) and confluent necrosis, many small
      basophilic hepatocytes surrounding large clear hepatocytes were positively
      stained in the areas next to the confluent necrosis. Therefore these small
      hepatocytes may be daughter cells derived from large clear hepatocytes that
      probably enter the mitotic cell cycle repeatedly to repair a large necrotic area.
      In the case of AVH with spotty necrosis, the positively stained hepatocytes were
      scattered around the necrotic foci. In the liver specimens from patients with
      chronic active hepatitis, most of the positively stained hepatocytes were located
      next to the necrotic area. As for cirrhosis of the liver, the number of
      hepatocytes positive for PCNA/cyclin varied greatly in different pseudolobules,
      and in the specimens of hepatocellular carcinoma (HCC), the HCC cells positive
      for PCNA/cyclin were detected throughout the cancer nests.

PMID- 1346736
TI  - Fertility after simulated Fowler-Stephens orchiopexy in rats.
AB  - In order to determine the effects of the Fowler-Stephens orchiopexy (FSO) on
      fertility, young rats underwent simulated FSO, FSO and concurrent contralateral
      orchiectomy (FSO/OR), unilateral orchiectomy (OR), or sham operation (controls).
      Twelve weeks after the operation, each male rat was mated to two proven-fertile
      female rats for 17 days (three ovulatory cycles). Two weeks later, both male and
      female rats were killed. No pregnancy resulted from the matings of the FSO/OR
      males. In contrast, pregnancy ensued in 13 of 16 (81%) females in the FSO group,
      9 of 14 (64%) in the OR group, and 11 of 12 (92%) in the control group. There
      were no fertile males in the FSO/OR group. In the FSO group, eight of eight males
      induced pregnancy in at least one female; in the OR group, six of seven (86%)
      males were fertile as were all six males in the control group. No differences in
      litter size or fetal weight were observed between fertile females in various
      groups.

PMID- 1346737
TI  - Use of cetirizine to investigate non-H1 effects of second-generation
      antihistamines.
AB  - In addition to their increased potency as H1 blockers and their nonsedating
      effects, the second-generation antihistamines have other unusual and potentially
      beneficial properties. Evidence is accumulating from several laboratories that at
      least one of these agents under investigation, cetirizine, may be effective in
      inhibiting the late reaction. The Johns Hopkins group showed that during the
      cutaneous late phase response (LPR), histamine release was not altered by
      cetirizine, 20 mg, pretreatment. The most dramatic effect of cetirizine was
      attenuation of inflammatory cell migration into the chamber. Eosinophils,
      neutrophils, and basophils were reduced by about 75% during hours 6 to 8. It can
      be concluded that cetirizine influences the LPR by causing a reduction in the
      inflammatory cell infiltrate. Cetirizine, 10 mg, orally once a day also induced a
      significant decrease in the wheal and flare skin reactions caused by pollen,
      histamine, and compound 48/80. Cetirizine inhibited eosinophil recruitment and
      platelet-activating factor (PAF) in skin chambers 24 hours after pollen
      challenge. We and others have studied the mechanisms of this effect. The release
      of eosinophil peroxidase induced by PAF and formyl-methionyleucyl/phenylalanine
      was not attenuated by cetirizine. At therapeutic concentrations, however,
      cetirizine has a potent inhibitory action in vitro on eosinophil chemotaxis
      induced either by formyl-methionyleucyl/phenylalanine or PAF and also on IgE
      dependent stimulation of platelets. In a separate study in patients with chronic
      urticaria, cetirizine markedly reduced both the immediate wheal and flare induced
      by PAF and the delayed reaction at six hours. These results suggest that
      cetirizine acts on eosinophil migration to inhibit the late reaction.

PMID- 1346738
TI  - Cystadenomas of the pancreas.
AB  - Five patients with cystadenoma of the pancreas were treated at two Connecticut
      hospitals between 1981 and 1987. All patients were women, with an average age of
      42 (range 29 to 64). Abdominal pain was the most common presenting complaint and
      was present in four of five patients; two patients had palpable abdominal masses.
      Four patients had serious cystadenomas; one patient had a mucinous cystadenoma.
      All patients were treated by resection (four distal pancreatectomies; one
      pancreaticoduodenectomy). All patients are alive and well 3 to 9 years following
      surgery. Nonoperative differentiation of benign from premalignant or malignant
      cystic pancreatic neoplasms can be extremely difficult. Unresected benign
      cystadenomas may undergo malignant degeneration or cause significant morbidity
      and mortality as a result of local complications. Complete resection, if
      possible, is the treatment of choice for these unusual lesions.

PMID- 1346739
TI  - Generalized cutaneous B-cell pseudolymphoma induced by neuroleptics.

PMID- 1346740
TI  - Norepinephrine-induced contractile responses in isolated rat aortae from
      different duration of diabetes.
AB  - The present study examined contractile responses to norepinephrine in isolated
      aortae from 4-, 8-, and 12-week duration of streptozocin-induced diabetic rats.
      The pD2 value and the maximum contractile responses were significantly increased
      in 8-week and 12-week diabetic aortae, respectively, compared to the age-matched
      control aortae. Moreover, the bethanechol-induced relaxation of 12-week diabetic
      aortae preconstricted with norepinephrine was also significantly different from
      the age-matched control aortae. On the other hand, the KCl-, phenylephrine
      induced contraction in 4-, 8-, and 12-week diabetic and age-matched control
      aortae were similar. Presumably the duration of diabetes altered the sensitivity
      and responsiveness of aortae to norepinephrine. The possibility of the enhanced
      norepinephrine response in diabetic aortae was discussed.

PMID- 1346741
TI  - Evolving concepts of partial agonism. The beta-adrenergic receptor as a paradigm.
AB  - The exact mechanism of receptor activation at the molecular level are still not
      known, nor do we completely understand the precise factors that distinguish
      agonist- and partial agonist-induced activation. Nevertheless, recent years have
      brought forth an explosion of new information regarding beta-adrenergic receptor
      structure and ligand-induced activation. Partial agonists are likely intermediate
      in their ability to interact with crucial serine residues (Ser204 and Ser207) on
      the beta-adrenergic receptor; these interactions allow either incomplete
      stimulation of the entire receptor population, or full stimulation of only a
      portion of the entire receptor population. From the work presented by Tota and
      Schimerlik for the muscarinic cholinergic receptor (another G-protein coupled
      receptor), it is likely that partial agonists induce or stabilize receptor
      conformations that have a lower affinity for their G protein compared to
      receptors stimulated by a full agonist. Molecular cloning of beta-adrenergic
      receptors and analyses of mutated and chimeric receptors expressed in transfected
      systems have indicated that domains of the receptor that bind agonists may be
      different from those with which antagonists interact. Thus, the ability of a
      partial agonist to interact with these two different domains may be a determinant
      of efficacy. Agonists alter the sulfhydryl redox status of the beta-adrenergic
      receptors in the presence of Gs. Disulfide rearrangement has been postulated to
      provide a structural constraint which biases G-protein-linked receptors in the
      "ground state" and may be important for stabilizing the active state of the
      receptor and holding the agonist/receptor/Gs ternary complex in the high-affinity
      state. Partial agonists induce this state less efficaciously or are less capable
      of holding the receptor in the active conformation to allow disulfide exchange to
      take place. The extent of receptor stimulation may dictate which G proteins are
      activated by a particular receptor, and thus which cellular effectors are
      stimulated. Alternatively, the level of activation of a receptor may translate
      into varying states of activation of a particular G protein (stabilized in part
      by disulfide bonds). Techniques such as fluorescence energy transfer in
      reconstitution systems or nuclear magnetic resonance spectroscopy should prove
      useful in distinguishing among these possible mechanisms. Ultimately, as a long
      term goal, X-ray crystallography of unoccupied receptors and receptors liganded
      by partial or full agonists may provide definitive insights. Although definitive
      answers are not yet possible, the rapid progress in understanding aspects of
      receptor structure allows a reformulation of ideas regarding the molecular basis
      of efficacy and partial agonism.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1346742
TI  - Regional expression of the homeobox gene Nkx-2.2 in the developing mammalian
      forebrain.
AB  - A novel mouse homeobox-containing gene, Nkx-2.2, has been isolated. Nkx-2.2 is a
      member of a family of genes whose homeodomains are homologous to that of the
      Drosophila NK-2 gene. Nkx-2.2 transcripts are found in localized domains of the
      brain during mouse embryogenesis. Nkx-2.2 expression in the brain abuts and
      partially overlaps with the expression domains of two other related homeobox
      containing genes, TTF-1 and Dlx. The expression domains of the three genes in the
      developing prosencephalon coincide with anatomical boundaries, particularly
      apparent in the diencephalon. This result raises the possibility that these genes
      may specify regional differentiation of the developing diencephalon into its
      anatomically and functionally defined subregions. Nkx-2.2 may be involved in
      specifying diencephalic neuromeric boundaries.

PMID- 1346743
TI  - Effect of pretreatment with oral pyridostigmine.

PMID- 1346744
TI  - Density of intrathecal agents.
AB  - The density of a drug in solution cannot be determined from a simple formula or
      from physicochemical tables, because it depends on the physical state of that
      substance in solution. The densities of agents which have been reported to be
      administered by the intrathecal route were measured at room and body
      temperatures. The results were compared with the density of cerebrospinal fluid.
      At room temperature, most drugs were isobaric with respect to cerebrospinal
      fluid, but as drugs warmed to body temperature they became relatively hypobaric.

PMID- 1346745
TI  - Effect of verapamil on the cardiovascular responses to tracheal intubation.
AB  - We have studied the efficacy of verapamil in attenuating the cardiovascular
      responses to tracheal intubation in three groups of ASA grade I patients given
      verapamil 0.05 mg kg-1 or 0.1 mg kg-1 or saline 45 s before the start of
      laryngoscopy. Anaesthesia was induced with thiopentone 5 mg kg-1 i.v. and
      tracheal intubation was facilitated with vecuronium 0.2 mg kg-1. During
      anaesthesia, ventilation was assisted or controlled with 1% enflurane and 50%
      nitrous oxide in oxygen. In patients who received saline, there was a significant
      increase in mean arterial pressure and rate-pressure product associated with
      tracheal intubation. The increases were significantly less in verapamil-treated
      patients compared with those in the control group, although verapamil failed to
      prevent tachycardia caused by laryngoscopy and intubation.

PMID- 1346746
TI  - Office sedation.

PMID- 1346747
TI  - Differential recognition of mdr1a and mdr1b gene products in multidrug resistant
      mouse tumour cell lines by different monoclonal antibodies.
AB  - An immunocytochemical method was used to test the reactivity of the anti-P
      glycoprotein antibodies, C219, MRK 16, JSB-1 and 265/F4 against multidrug
      resistant (MDR) variants derived from the human small cell lung carcinoma line,
      NCI-H69, the mouse fibrosarcoma line, RIF-1 and the mouse mammary tumour cell
      line, EMT6. C219 produced positive staining in MDR variants of both human and
      mouse tumour cell lines. MRK 16 and JSB-1 however recognised P-glycoprotein only
      in the human MDR cell lines and not in the mouse MDR cells. 265/F4 appeared the
      most selective of the monoclonal antibodies used, producing positive staining of
      MDR variants derived from the RIF-1 line, but not of MDR variants derived from
      the EMT6 line. Total RNA was prepared from the mouse cell lines and, following
      reverse transcription, cDNA sequences were amplified by the polymerase chain
      reaction with primers specific for either the murine mdr1a or the mdr1b genes.
      From this it was possible to show that only the mdr1a gene is overexpressed in
      the resistant EMT6 lines that do not stain with 265/F4 whereas both mdr1a and
      mdr1b are overexpressed in the positively staining resistant fibrosarcoma line,
      RIF/1.0. Low level expression of mdr1b was detected in the sensitive parent RIF-1
      cells and increasing levels of expression correlated with increasing resistance
      in the lines, RIF/0.1, 0.2, 0.4 and 1.0. Expression of mdr1a was found only in
      the more resistant fibrosarcoma cell lines. It seems that 265/F4 recognises only
      the mdr1b P-glycoprotein. Western blotting confirmed that this antibody detects a
      170 kDa protein only in membranes derived from the resistant fibrosarcoma cells.
      265/F4 may thus be used to distinguish between the murine P-glycoprotein isoforms
      so revealing differences between tumour cell lines in cellular localisation and
      in the time of appearance of mdr1a and mdr1b P-glycoprotein following drug
      exposure.

PMID- 1346748
TI  - Response to mitoxantrone in advanced breast cancer: correlation with expression
      of c-erbB-2 protein and glutathione S-transferases.
AB  - Sixty-eight patients with advanced breast cancer were treated with mitoxantrone
      and clinical responses assessed. Expression of c-erbB-2 protein and cytosolic
      glutathione S-transferase (GST) isoenzymes pi, alpha and mu by the primary
      tumours of these patients was determined immunohistochemically, and correlated
      with treatment response. Tumours overexpressing c-erbB-2 (n = 16, 23%) showed a
      lower response rate (50% vs 58%) and shorter duration of response to treatment,
      compared with c-erbB-2 negative tumours. These associations were not
      statistically significant but survival following start of treatment was
      significantly shorter in the c-erbB-2 positive group. For each GST isoenzyme, the
      response rate and duration of response of the group showing enzyme expression did
      not differ significantly from those with negatively staining tumours. These data
      do not support a role for expression of GSTs alone in resistance to mitoxantrone
      monotherapy in advanced breast cancer. The poorer post treatment survival of
      patients with c-erbB-2 positive tumours suggests they could be selected for more
      intensive treatment regimens.

PMID- 1346749
TI  - Influence of the size and protonation state of acidic residue 85 on the
      absorption spectrum and photoreaction of the bacteriorhodopsin chromophore.
AB  - The consequences of replacing Asp-85 with glutamate in bacteriorhodopsin, as
      expressed in Halobacterium sp. GRB, were investigated. Similarly to the in vitro
      mutated and in Escherichia coli expressed protein, the chromophore was found to
      exist as a mixture of blue (absorption maximum 615 nm) and red (532 nm) forms,
      depending on the pH. However, we found two widely separated pKa values (about 5.4
      and 10.4 without added salt), arguing for two blue and two red forms in separate
      equilibria. Both blue and red forms of the protein are in the two-dimensional
      crystalline state. A single pKa, such as in the E. coli expressed protein, was
      observed only after solubilization with detergent. The photocycle of the blue
      forms was determined at pH 4.0 with 610 nm photoexcitation, and that of the red
      forms at pH 10.5 and with 520 nm photoexcitation, in the time-range of 100 ns to
      1 s. The blue forms produced no M, but a K- and an L-like intermediate, whose
      spectra and kinetics resembled those of blue wild-type bacteriorhodopsin below pH
      3. The red forms produced a K-like intermediate, as well as M and N. Only the red
      forms transported protons. Specific perturbation of the neighborhood of the
      Schiff base by the replacement of Asp-85 with glutamate was suggested by (1) the
      shift and splitting of the pKa for what is presumably the protonation of residue
      85, (2) a 36 nm blue-shift in the absorption of the all-trans red chromophore and
      a 25 nm red-shift of the 13-cis N chromophore, as compared to wild-type
      bacteriorhodopsin and its N intermediate, and (3) significant acceleration of the
      deprotonation of the Schiff base at pH 7, but not of its reprotonation and the
      following steps in the photocycle.

PMID- 1346750
TI  - Electron microscopy and image analysis of the GroEL-like protein and its
      complexes with glutamine synthetase from pea leaves.
AB  - The molecular structure of GroEL-like protein from pea leaves has been studied by
      electron microscopy and image analysis of negatively stained particles. Over 1500
      molecular projections were selected and classified by multivariate statistical
      analysis. It was shown that the molecule consists of 14 subunits arranged in two
      layers with 72 point group symmetry. Side view projections of the molecule show a
      four-striation appearance, which subdivides both layers of seven subunits into
      two halves; this may be explained by a two-domain structure of the subunits. The
      presence in protein preparations of projections corresponding to one layer of
      subunits or half-molecules is consistent with the molecular structure suggested.
      Electron microscopic evidence for a specific association of GroEL-like protein
      and octameric glutamine synthetase, which was co-purified with this protein, was
      obtained.

PMID- 1346751
TI  - The presence of free D-alanine, D-proline and D-serine in mice.
AB  - The presence of free D-alanine, D-proline and D-serine was demonstrated in
      mammalian tissues, using a mutant mouse strain lacking D-amino acid oxidase. In
      the experiment, free amino acids from the kidney and serum were derivatized with
      1-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA) to diastereomers, separated
      by two-dimensional thin-layer chromatography (TLC), and analysed by reversed
      phase high-performance liquid chromatography (HPLC) for the resolution of D- and
      L-isomers. D/L ratios of alanine, proline and serine were obtained based on the
      peak areas of HPLC.

PMID- 1346752
TI  - Variability in serial CD4 counts and relation to progression of HIV-I infection
      to AIDS in haemophilic patients. Transfusion Safety Study Group.
AB  - OBJECTIVE--To examine the CD4 count and its near term changes relative to
      progression to AIDS within 30 months and to subsequent CD4 counts. DESIGN-
      Longitudinal clinical and laboratory study. SETTING--Haemophilia treatment
      centres in six large American cities. PATIENTS--555 people with congenital
      clotting disorders who were infected with HIV, initially without AIDS, and seen
      at follow up for 6-30 months in 1986-9. MAIN OUTCOME MEASURES--Absolute CD4
      counts and incidence of AIDS. RESULTS--Outset CD4 count and age were
      independently related to progression to AIDS (p less than 0.0001 and p less than
      0.005 respectively). Patients with CD4 counts of 0.30-0.49 x 10(9) cells/l had an
      age adjusted risk of AIDS within 30 months of only 9% that of patients with
      counts less than 0.20 x 10(9)/l. Children under 10 years old had only 16% of the
      CD4 adjusted risk of AIDS of people aged greater than or equal to 45 years.
      Analysis of 149 patients' CD4 counts at the beginning and end of two successive
      six month intervals showed an average decrease of 11% in each six months
      regardless of the outset count (greater than or equal to 0.20 x 10(9)/l). For
      individual patients the decrease in the second six month period was unaffected by
      the decrease in the first six month period. CONCLUSIONS--Antiviral treatment of
      asymptomatic people, particularly children, with CD4 counts greater than or equal
      to 0.3 x 10(9)/l is questionable if predicted on near term progression to AIDS.
      Because of individual CD4 count variability and the low rate of progression to
      AIDS near term declines in individual CD4 counts are a poor index for identifying
      people who will rapidly progress to AIDS.

PMID- 1346753
TI  - Advances in neuropharmacological rehabilitation for brain dysfunction.
AB  - The use of pharmacological agents as rehabilitative tools following brain injury
      remains to some degree both a science and an art. Recent work in the area of the
      neural sciences has shed new light on the workings of basic CNS neurochemical
      systems and the use of pharmacologic agents in altering central neurophysiologic
      processes. The major central neurochemical systems are reviewed both anatomically
      and physiologically. An overview is provided of basic neuropharmacologic agents
      by class. Lastly, some of the newer neuropharmacological options for treatment of
      post-acute brain injury deficits are examined.

PMID- 1346754
TI  - Twin of I-POU: a two amino acid difference in the I-POU homeodomain distinguishes
      an activator from an inhibitor of transcription.
AB  - I-POU, a POU domain nuclear protein that lacks two conserved basic amino acids of
      the POU homeodomain is coexpressed in the developing Drosophila nervous system
      with a second POU domain transcription factor, Cf1-a. I-POU does not bind to DNA
      but forms a POU domain-mediated, high affinity heterodimer with Cf1-a, inhibiting
      its ability to bind and activate the dopa decarboxylase gene. The I-POU/Cf1-a
      dimerization interface encompasses only the N-terminal basic region and helices 1
      and 2 of the POU homeodomains with precise amino acid and alpha-helical
      requirements. twin of I-POU, an alternatively spliced transcript of the I-POU
      gene, encodes a protein containing the two basic amino acid residues absent in I
      POU. Twin of I-POU is incapable of dimerizing with Cf1-a, but can act as a
      positive transcription factor on targets distinct from those regulated by Cf1-a.
      These findings suggest that the I-POU genomic locus simultaneously generates both
      a specific activator and inhibitor of gene transcription, capable of modulating
      two distinct regulatory programs during neural development.

PMID- 1346755
TI  - brahma: a regulator of Drosophila homeotic genes structurally related to the
      yeast transcriptional activator SNF2/SWI2.
AB  - The brahma (brm) gene is required for the activation of multiple homeotic genes
      in Drosophila. Loss-of-function brm mutations suppress mutations in Polycomb, a
      repressor of homeotic genes, and cause developmental defects similar to those
      arising from insufficient expression of the homeotic genes of the Antennapedia
      and Bithorax complexes. The brm gene encodes a 1638 residue protein that is
      similar to SNF2/SWI2, a protein involved in transcriptional activation in yeast,
      suggesting possible models for the role of brm in the transcriptional activation
      of homeotic genes. In addition, both brm and SNF2 contain a 77 amino acid motif
      that is found in other Drosophila, yeast, and human regulatory proteins and may
      be characteristic of a new family of regulatory proteins.

PMID- 1346756
TI  - The homeotic gene APETALA3 of Arabidopsis thaliana encodes a MADS box and is
      expressed in petals and stamens.
AB  - Mutations in the APETALA3 (AP3) gene of A. thaliana result in homeotic
      transformations of petals to sepals and stamens to carpels. We have cloned the
      AP3 gene from Arabidopsis based on its homology to the homeotic flower gene
      deficiens (DEFA) from the distantly related plant Antirrhinum majus. The sequence
      of four ap3 mutant alleles and genetic mapping analysis prove that the DEFA
      homolog is AP3. Like several other plant homeotic genes, the AP3 gene contains a
      MADS box and likely acts as a transcription factor. The region-specific spatial
      expression pattern of AP3 rules out certain types of sequential models of flower
      development and argues in favor of a spatial model based on positional
      information. Since DEFA and AP3 have very similar protein products, mutant
      phenotypes, and spatial expression patterns, it is likely that these genes are
      cognate homologs.

PMID- 1346757
TI  - Influence of different levels of dietary casein on initiation of male rat liver
      carcinogenesis with a single dose of aflatoxin B1.
AB  - To analyze the influence of different levels of dietary casein on the initiation
      process, male Wistar rats, pair-fed on isocaloric diets containing 5, 15 or 40%
      casein were initiated with a single dose of aflatoxin B1, 28 days after the
      experimental start. From day 4 after initiation and until selection of initiated
      cells was started, 25 days later, rats were fed the 15% casein diet, providing an
      identical dietary background during the selection period. Promotion/selection of
      initiated cells was performed by the combined treatment with 0.02% 2
      acetylaminofluorene in the 15% casein diet for 2 weeks and a two-thirds partial
      hepatectomy (PH) in the middle of this period. The number of enzyme-altered
      hepatic lesions per rat was shown to increase with increasing content of casein
      in the diet, both when liver sections were stained for gamma-glutamyltransferase
      and with immunohistochemical staining for the placental form of glutathione-S
      transferase. Non-initiated rats fed the different levels of casein exhibited a
      very low number of foci. Livers were secured also from non-initiated rats at the
      same point of time as initiation was performed. Whereas no significant
      differences in the total microsomal content of cytochrome P450 were observed, a
      higher microsomal capacity to perform 16 alpha-hydroxylation of 4-androstene-3,17
      dione was observed in preparations from rats fed 40% casein, when compared with
      rats receiving the 5% casein diet. The dietary protein content at the time of
      initiation did not affect the expression of the c-rasHa, c-myc or c-fos
      protooncogenes, either at initiation, on day 3, or at PH.

PMID- 1346758
TI  - Fourth International Conference on Chemistry and Biology of Mineralized Tissues.
      Coronado, California, February 5-9, 1992. Abstracts.

PMID- 1346759
TI  - Autocrine growth induced by kinase type oncogenes in myeloid cells requires AP-1
      and NF-M, a myeloid specific, C/EBP-like factor.
AB  - The nuclear oncogenes v-myc or v-myb specifically transform avian myeloid cells.
      In both cases, the transformed cells remain dependent on chicken myelomonocytic
      growth factor (cMGF). This factor dependence can be relieved by expression of
      kinase-type oncogenes such as v-mil or v-erbB, leading to expression of cMGF and
      autocrine growth stimulation. In erythroid cells the same kinase-type oncogenes
      cause transformation but do not induce cMGF expression. Here we investigated the
      molecular mechanisms of the observed lineage specific oncogene collaboration. We
      found that kinase-type oncogenes and TPA activate the cMGF promoter via AP-1 like
      transcription factors. The activation of the cMGF promoter is, however, strictly
      dependent on the binding of nuclear proteins to both halves of an inverted repeat
      adjacent to the AP-1 binding site. These proteins are related to C/EBP. They are
      expressed exclusively in myeloid cells and were therefore termed NF-M. Our
      results indicate that the lineage specific cooperation of kinase type oncogenes
      with v-myb or v-myc in leukemia formation is based on the concerted action of AP
      1 and NF-M on the cMGF promoter.

PMID- 1346760
TI  - Characterization of the Antirrhinum floral homeotic MADS-box gene deficiens:
      evidence for DNA binding and autoregulation of its persistent expression
      throughout flower development.
AB  - We have determined the structure of the floral homeotic deficiens (defA) gene
      whose mutants display sepaloid petals and carpelloid stamens, and have analysed
      its spatial and temporal expression pattern. In addition, several mutant alleles
      (morphoalleles) were studied. The results of these analyses define three
      functional domains of the DEF A protein and identify in the deficiens promoter a
      possible cis-acting binding site for a transcription factor which specifically
      upregulates expression of deficiens in petals and stamens. In vitro DNA binding
      studies show that DEF A binds to specific DNA motifs as a heterodimer, together
      with the protein product of the floral homeotic globosa gene, thus demonstrating
      that the protein encoded by deficiens is a DNA binding protein. Furthermore,
      Northern analysis of a temperature sensitive allele at permissive and non
      permissive temperatures provides evidence for autoregulation of the persistent
      expression of deficiens throughout flower development. A possible mechanism of
      autoregulation is discussed.

PMID- 1346761
TI  - The upstream region of the human homeobox gene HOX3D is a target for regulation
      by retinoic acid and HOX homeoproteins.
AB  - We studied the structure, regulation and expression of HOX3D, a human homeobox
      gene located in the HOX3 cluster on chromosome 12. HOX3D is developmentally
      regulated during embryogenesis and is activated by retinoic acid (RA) in cultured
      embryonal carcinoma (EC) cells. Transfection of HOX3D upstream genomic sequences
      linked to a reporter gene allowed the functional definition of its promoter,
      containing a canonical TATA element. This promoter directs the expression of the
      reporter gene in EC cells after induction with RA, and binds RA-induced nuclear
      factor(s) through a conserved palindromic sequence located approximately 100 bp
      upstream of the transcription start site. The HOX3D promoter is transactivated in
      both human and murine cells when cotransfected with vectors expressing the
      protein product of the upstream gene HOX3C and the paralogs of further upstream
      genes in the HOX4 cluster (i.e. HOX4D, HOX4C and the murine Hox 4.3). The HOX3D
      protein, and those encoded by the downstream gene HOX3E and its paralog HOX4B are
      instead inactive. HOX4C and HOX4D proteins synthesized in bacteria bind to the
      same conserved sequence located around position -120, as well as to the TATA box
      and immediately upstream and downstream nucleotides. These data provide evidence
      that cross-regulatory interactions between mammalian homeogenes take place in
      cultured cells, thus raising the possibility that a regulatory network may exist
      in vivo. The sequences on the HOX3D promoter involved in cross-regulation are
      different from those binding nuclear factors induced by RA.

PMID- 1346764
TI  - Isolation and amino acid sequence of a glutamic acid specific endopeptidase from
      Bacillus licheniformis.
AB  - An endopeptidase cleaving specifically at the carboxyl side of acidic amino acid
      residues, preferentially at glutamic acid, has been isolated from a commercial
      extract obtained by fermentation with Bacillus licheniformis. Using ion-exchange
      chromatography and affinity chromatography on bacitracin-Sepharose, it was
      possible, from 100 ml commercial extract, to isolate 100 mg homogeneous enzyme in
      a yield of 50%. It is the first description of a large-scale isolation of a
      Glu/Asp-specific enzyme. The preparation was essentially free of contaminating
      activities. The isolated enzyme consists of one peptide chain of 222 amino acid
      residues and has a calculated molecular mass of 23,589 Da. The determined amino
      acid sequence shows similarity to the Glu/Asp-specific enzymes previously
      isolated from Staphylococcus aureus V8, Actinomyces sp. and Streptomyces
      thermovulgaris. The substrate preference of the enzyme has been investigated.
      Although non-specific cleavages were observed after prolonged hydrolysis at high
      enzyme concentrations the enzyme appears to be essentially specific for Glu-Xaa
      and Asp-Xaa, with strong preference for the former. The isolated enzyme exhibits
      a bell-shaped pH/activity profile with an optimum at pH 7.5-8.0. The activity is
      adversely affected by high ionic strength and beneficially affected by the
      inclusion of calcium ions in the assay medium. The enzyme is completely inhibited
      by diisopropylfluorophosphate, suggesting that it is a serine endopeptidase. It
      is partially inhibited by EDTA.

PMID- 1346762
TI  - Distamycin-induced inhibition of homeodomain-DNA complexes.
AB  - The mobility shift assay was used to study the competition of the minor groove
      binder distamycin A with either an Antennapedia homeodomain (Antp HD) peptide or
      derivatives of a fushi tarazu homeodomain (ftz HD) peptide for their AT-rich DNA
      binding site. The results show that distamycin and the homeodomain peptides
      compete under the conditions: (i) preincubation of DNA with distamycin and
      subsequent addition of HD peptide; (ii) simultaneous incubation of DNA with
      distamycin and HD peptide; and (iii) preincubation of DNA with HD peptide and
      subsequent addition of distamycin. There is also competition when using a peptide
      which lacks the N-terminal arm of ftz HD that is involved in contacts in the
      minor groove. It is proposed that the protein's binding affinity is diminished by
      distamycin-induced conformational changes of the DNA. The feasibility of the
      propagation of conformational changes upon binding in the minor groove is also
      shown for the inhibition of restriction endonucleases differing in the AT content
      of their recognition site and of their flanking DNA sequences. Thus, it is
      demonstrated that minor groove binders can compete with the binding of proteins
      in the major groove, providing an experimental indication for the influence of
      biological activities exerted by DNA ligands binding in the minor groove.

PMID- 1346763
TI  - Three dimensional structure of the transmembrane region of the proto-oncogenic
      and oncogenic forms of the neu protein.
AB  - The neu proto-oncogene may be converted into a dominantly transforming oncogene
      by a single point mutation. Substitution of a valine residue at position 664 in
      the transmembrane region with glutamic acid activates the tyrosine kinase of the
      molecule and is associated with increased receptor dimerization. Previously we
      have proposed a model in which the glutamic acid side chain stabilizes receptor
      dimerization by hydrogen bonding. Other models have been proposed in which the
      mutation leads to a conformational change in the transmembrane region mimicking
      that assumed to occur following binding of a natural ligand. Synthetic peptides
      representing part of the transmembrane region were prepared. Some residues were
      replaced with serine in order to improve peptide solubility to allow purification
      and analysis. Both the peptides containing valine and glutamic acid dissolved in
      water and in an artificial lipid monolayer. The structures of the peptides were
      determined by NMR spectroscopy to be alpha-helical. No significant difference in
      conformation was observed between the two peptides. This result does not support
      the model proposing a conformational change. The receptor structures determined
      experimentally do allow alternative models involving receptor transmembrane
      region packing.

PMID- 1346765
TI  - Periportal zonation of the cytosolic acetyl-CoA synthetase of male rat liver.
AB  - Several important metabolic functions of the mammalian liver have been shown to
      be located in zones with respect to the complex microcirculation of the organ.
      The zonal distribution of the cytosolic component of the acetyl-CoA synthetase
      activity has been investigated using the dual-digitonin-pulse-perfusion
      technique, which allows highly zone-selective sampling of cytosol from the
      periportal and perivenous zone of rat liver. Approximately 80% of the cytosolic
      enzymes are eluted from the hepatocytes in the periportal and perivenous sub
      zones affected by digitonin, while less than 1% of the glutamate dehydrogenase
      activity (a marker enzyme of the mitochondrial compartment) is eluted. A twofold
      higher activity of the cytosolic form of acetyl-CoA synthetase is found in the
      periportal zone compared to the perivenous zone in fed male rats. Following a
      fasting/refeeding transition, this activity gradient is abolished in a manner
      similar to that observed for the enzyme acetyl-CoA carboxylase. Since the latter
      enzyme is utilizing the product of acetyl-CoA synthetase, acetyl-CoA, the
      similarity in the observed regulation suggests a functional coupling between
      cytosolic acetate activation and fatty-acid synthesis.

PMID- 1346766
TI  - Plasmodium falciparum: in vitro characterization and human infectivity of a
      cloned line.
AB  - The culture-adapted NF54 isolate of Plasmodium falciparum was subjected in vitro
      to three sequential limiting dilution titrations and the resulting clone was
      given the designation CVD1. DNA sequence analysis of the gene encoding the
      circumsporozoite (CS) protein revealed differences between CVD1 and the published
      NF54 CS gene. CVD1 had 1191 bp, 397 amino acids, and 42 repeat units while NF54
      had 1218 bp, 405 amino acids, and 44 repeat units. The CVD1 clone was more
      sensitive to chloroquine than was the parental line, in vitro. Anopheles
      stephensi mosquitoes were infected equally by the cloned and uncloned parasites.
      Volunteers were readily infected by NF54 and CVD1 following infectious mosquito
      bites. The availability of a well-characterized, chloroquine-sensitive clone
      which safety infects humans should facilitate performance of experimental
      challenge studies to assess vaccine efficacy.

PMID- 1346767
TI  - Entamoeba histolytica extrachromosomal circular ribosomal DNA: analysis of clonal
      variation in a hypervariable region.
AB  - The ribosomal RNA genes of the protozoan parasite Entamoeba histolytica are
      highly repeated and display restriction fragment length polymorphism. Using a set
      of four DNA probes spanning the coding region and part of the flanking region of
      the E. histolytica ribosomal RNA genes, an analysis of the DNA bands generated by
      EcoRI digestion of Entamoeba DNA is presented. This analysis included five
      strains of E. histolytica, four strains of E. moshkovskii, and one strain each of
      E. invadens and E. terrapinae. No common bands were observed between E.
      histolytica and the other Entamoeba. Within E. histolytica, two bands were
      conserved in all strains while the others were polymorphic. Detailed analysis of
      DNA from independently isolated clones of the strain HM-1:IMSS of E. histolytica
      showed two bands to be highly polymorphic. Of these, the 4.4-kb band of clone 6
      was further analyzed. Polymorphism in this band could even be demonstrated in
      cells of the same clone. Restriction enzyme analysis of this DNA band from two
      clones of HM-1:IMSS showed that the polymorphism may be due to variable numbers
      of DraI repeat units present in this DNA stretch.

PMID- 1346768
TI  - Subtypes of alpha 1- and alpha 2-adrenergic receptors.
AB  - The adrenergic receptors are members of the superfamily of G protein-coupled
      receptors. There are three major types of adrenergic receptors: alpha 1, alpha 2,
      and beta. Each of these three major types can be divided into three subtypes.
      Within the alpha 1-adrenergic receptors, alpha 1A and alpha 1B subtypes have been
      defined pharmacologically on the basis of reversible antagonists, such as WB4101
      and phentolamine, and the irreversible antagonist chloroethylclonidine. In at
      least some tissues the mechanism of action of the alpha 1A subtype is related to
      activation of a calcium channel, whereas the alpha 1B receptor exerts its effect
      through the second messenger inositol trisphosphate. Both of these receptor
      subtypes as well as a third, the alpha 1C, have been identified by molecular
      cloning. Three pharmacological subtypes of the alpha 2-adrenergic receptor have
      also been identified. Prototypic tissues and cell lines in continuous culture
      have been developed for each of these subtypes, which facilitated their study.
      The definition of the alpha 2 subtypes has been based on radioligand binding data
      and more limited functional data. All three subtypes have been shown to inhibit
      the activation of adenylate cyclase and thus reduce the levels of cAMP. Three
      alpha 2-adrenergic receptor subtypes have been identified by molecular cloning in
      both the human and rat species. There is reasonable agreement between the
      pharmacological identified subtypes and those identified by molecular cloning.

PMID- 1346770
TI  - Teaching pathology to medical students in the 1990s: a 1989 symposium of the
      Association of Pathology Chairmen.

PMID- 1346769
TI  - Role of gastric acid suppression in the treatment of gastro-oesophageal reflux
      disease.
AB  - Gastro-oesophageal reflux disease is a common condition with a complex
      pathophysiology. Despite the spectrum of abnormalities, gastric acid has a
      central role in mucosal damage, and the mainstay of medical treatment is
      suppression of gastric acid secretion. The results of antisecretory treatment as
      assessed by endoscopic healing are reviewed. H2 receptor antagonists give more
      rapid symptom relief than placebo and can produce endoscopic improvement in 31
      88% of cases depending on the severity of oesophagitis. Complete healing,
      however, is seen only in 27-45% of patients and these have mainly grades I-II
      disease. Improved healing rates can be obtained by increasing the degree of acid
      suppression or the length of treatment. The addition of a prokinetic agent may be
      beneficial. Omeprazole heals 67-92% of patients overall and although most
      successful in the lower grades of oesophagitis, can also heal 48-62% of patients
      with grade IV disease. The degree and rate of healing seem to be related to the
      reduction in oesophageal acid exposure and thus may correlate with the degree and
      duration of acid suppression over 24 hours obtained by the various treatments.
      The underlying pathophysiology is unchanged, however, and long term treatment may
      be needed to maintain remission.

PMID- 1346771
TI  - Allelic dimorphism in the human tissue-type plasminogen activator (TPA) gene as a
      result of an Alu insertion/deletion event.
AB  - Polymerase chain reaction and direct sequencing were used to investigate an
      amplified DNA fragment containing the suspected polymorphic site of all known
      intragenic restriction fragment length polymorphisms (RFLPs) within the human
      tissue-type plasminogen activator (TPA) gene. Sequence data obtained showed that
      these RFLPs were all generated by the presence or absence of one of the two Alu
      sequences located in intron h of the human TPA gene. Furthermore, one of the
      direct repeats flanking this Alu sequence was absent in the minor allele. In
      addition to indicating the presence of an Alu insertion in an ancestral human TPA
      gene, these findings suggest a slip-replication mechanism for the deletion of
      this Alu repeat, once inserted into the gene. As both alleles have been observed
      in similar frequencies among different ethnic groups, the insertion or subsequent
      deletion of this Alu sequence in the human TPA gene must have occurred early in
      human evolution.

PMID- 1346772
TI  - Haplotype analysis at the low density lipoprotein receptor locus: application to
      the study of familial hypercholesterolemia in Israel.
AB  - Familial hypercholesterolemia (FH) results from mutations in the low density
      lipoprotein (LDL) receptor gene. It has been shown that restriction fragment
      length polymorphisms (RFLPs) associated with this gene may be used for family and
      population studies. The present investigation is a population-based study of 19
      Jewish families with hypercholesterolemia representing 9 different countries of
      origin. Ten RFLP sites were used to construct 24 different haplotypes from 112
      chromosomes. These haplotypes vary in frequency from 0.9% to 28.6%. Five
      previously undescribed haplotypes, which comprise 8.1% of the sample, are
      reported here. The six most common haplotypes account for 70% of the sample.
      Segregation analysis reveals that, in Israel, distinct LDL receptor haplotypes
      are associated with hypercholesterolemia in 12 (63%) out of the 19 Jewish
      families. Five LDL receptor haplotypes co-segregate with hypercholesterolemia.
      Two of these haplotypes seem to be unique to specific population groups in Israel
      and may therefore represent founder mutations.

PMID- 1346773
TI  - The Wiskott-Aldrich syndrome: refinement of the localization on Xp and
      identification of another closely linked marker locus, OATL1.
AB  - The Wiskott-Aldrich syndrome (WAS) has previously been mapped to the proximal
      short arm of the X chromosome between the DXS14 and DXS7 loci. In this study,
      further segregation analysis has been performed using a newly identified WAS
      family as well as an additional marker probe, HOATL1. The results indicate close
      linkage between the WAS and OATL1 loci (Z = 6.08 at theta = 0.00) and localize
      the TIMP, OATL1, DXS255, and WAS loci distal to DXS146 and the OATL1 and WAS loci
      proximal to TIMP. These linkage data narrow the boundaries within which the WAS
      locus maps to the chromosomal region bracketed by TIMP and DXS146 and support the
      loci order Xpter-DXS7-TIMP-(OATL1, WAS, DXS255)-DXS146.

PMID- 1346774
TI  - Association of apolipoprotein B gene variants with plasma apoB and low density
      lipoprotein (LDL) cholesterol levels.
AB  - The contribution of the variants of the apolipoprotein (apo) B locus to the total
      variance in plasma apoB and cholesterol levels was examined in four independent
      populations, two that were composed of normal controls (n = 77 and 85) and two
      with coronary heart disease (n = 115 and 159). A correlation between genotype at
      the apoB-XbaI locus and apoB levels was observed. The effects of the (+; presence
      of restriction site) and (-) alleles were to increase or decrease the apoB and
      cholesterol levels by approximately 3.5 mg/dl, respectively. None of the 274
      individuals in the coronary heart disease (CHD) groups was found to be a carrier
      of the apoB allele Arg3500----Gln, previously shown to be associated with an apoB
      protein defective in binding to the low density lipoprotein receptor (LDL-R). No
      DNA sequence variants were found in the region encoding amino acid residues 3129
      3532 within the putative LDL-R binding domain among 35 individuals with apoB
      levels above the 94th percentile (141 mg/dl).

PMID- 1346775
TI  - PCR-based RFLP analysis allows genotyping of the short arm of chromosome 3 in
      small biopsies from patients with lung cancer.
AB  - The tumors of patients with lung cancers often show loss of heterozygosity (LOH)
      at polymorphic loci on the short arm of chromosome 3. Most examples of small-cell
      lung carcinoma (SCLC) cannot be examined since they are infrequently resected.
      Small biopsies are, however, usually available from patients with this disease.
      We have used the polymerase chain reaction (PCR) to study lung tumor biopsies
      obtained by fiberoptic bronchoscopy and assign the genotype at 11 RFLPs in 7 well
      established loci on 3p. We have demonstrated LOH in some and found that biopsy
      samples need to contain approximately 60% content of tumor cells if LOH is to be
      reliably detected. One SCLC tumor that we examined has an interstitial 3p
      deletion proximal to the locus D3F15S2 and thus provides information useful in
      mapping the position of the tumor suppressor gene on 3p.

PMID- 1346776
TI  - Chromosomal mapping of the human annexin IV (ANX4) gene.
AB  - Annexin IV (placental anticoagulant protein II) is a member of the annexin or
      lipocortin family of calcium-dependent phospholipid-binding proteins. A cDNA for
      human annexin IV was isolated from a placental library that is 675 bases longer
      in the 3' untranslated region than previously reported, indicating the existence
      of alternative mRNA processing for this gene. Genomic Southern blotting with a
      cDNA probe indicated a gene size of 18-56 kb. Primers developed for polymerase
      chain reaction (PCR) allowed amplification of a 1.6-kb portion of the ANX4 gene.
      DNA sequence analysis showed that this PCR product contained a single intron with
      exon-intron boundaries in exactly the same position as in the mouse annexin I and
      annexin II genes. PCR analysis of a somatic cell hybrid panel mapped the ANX4
      gene to chromosome 2, and in situ hybridization with a cDNA probe showed a unique
      locus for ANX4 at 2p13. This study provides further evidence that genes for the
      annexins are dispersed throughout the genome but are similar in size and exon
      intron organization.

PMID- 1346777
TI  - Linkage analysis of spinal muscular atrophy.
AB  - Linkage data between four markers on chromosome 5 confirm and extend our previous
      studies that localized the mutation in spinal muscular atrophy to 5q11.2-q13.3.
      Localization of D5S6 by in situ hybridization refines the mapping of the
      defective gene to the region 5q12.2-q13. We also report the use of a highly
      informative PCR-based polymorphism with five alleles. This RFLP will be
      particularly useful for prenatal diagnosis where only old tissue samples from
      affected individuals are available. The high heterozygosity of this locus should
      also assist in identifying recombinants that will refine the genetic mapping of
      the mutation.

PMID- 1346778
TI  - Mouse genomic DNA sequences homologous to sea urchin TU elements are genetically
      stable polydispersed repeats useful for analysis of multiple RFLPs.
AB  - Segments of the murine genome that hybridize to the inverted repeat regions of
      the transposable TU elements of sea urchins include tandem repeats of a sequence
      (CTCC) that encodes the recognition site for the restriction enzyme Mnl1, as do
      the analogous polypurine/polypyrimidine (pPu/pPy) stretches in humans. The Mnl1
      sensitive repeats, which exist as a microsatellite sequence 200-300 bp in length,
      lack the terminal dyad symmetry characteristic of the TU elements and are
      structurally and functionally distinct from these elements. DNA fragments
      containing these repeat units that are isolated from different generations of
      isogenic (or congenic) mice or from different tissues of genetically identical
      individuals are indistinguishable by RFLP analysis; however, they show
      restriction fragment length polymorphism in different strains. This polymorphism
      appears to reflect DNA sequence changes occurring at sites flanking the repeats
      rather than variability in the number of repeats. Their genetic stability and
      occurrence in a wide variety of animal species make the Mnl1 repeats useful in
      studying genetic variation that has occurred over an evolutionary time scale of
      greater duration than can be examined conveniently by VNTR analysis.

PMID- 1346779
TI  - Chromosomal localization of three pulmonary surfactant protein genes in the
      mouse.
AB  - Pulmonary surfactant, a protein-phospholipid mixture, maintains surface tension
      at the lung epithelium/air interface preventing alveolar collapse during
      respiration. For mammals appropriate developmental production of surfactant is
      necessary for adaptation to the air breathing environment. Deficiency of
      pulmonary surfactant results in respiratory distress syndrome (RDS), a leading
      cause of death in premature infants. Recently, three lung-specific pulmonary
      surfactant proteins designated SP-A, SP-B, and SP-C have been described. Cloned
      sequences for the genes that encode each of these proteins have been partially
      characterized in humans and other species. Analysis of interspecific backcross
      mice has allowed us to map the chromosomal locations of these three genes in the
      mouse. The gene encoding SP-A (Sftp-1) and the gene encoding SP-C (Sftp-2) both
      map to mouse chromosome 14, although at separate locations, while the gene
      encoding SP-B (Sftp-3) maps to chromosome 6. The mouse map locations determined
      in this study for the Sftp genes are consistent with the locations of these genes
      on the human genetic map and the syntenic relationships between the human and the
      mouse genomes.

PMID- 1346780
TI  - Physical mapping of a 950-kb region surrounding a locus (D10S102) tightly linked
      to the MEN2A gene.
AB  - We have constructed a long-range contig of cosmid and YAC clones around D10S102,
      a locus that is tightly linked to the gene responsible for multiple endocrine
      neoplasia type 2A (MEN2A). With D10S102 as a starting point, a 360-kb cosmid
      contig was constructed by bidirectional genomic walking, and at least six
      fragments from these cosmids showed high sequence homology to other species. Five
      YAC clones were also isolated at the D10S102 locus, and they formed a contig
      covering 950 kb of genomic DNA. Furthermore, we obtained six RFLP systems from
      the contig, which will serve as new resources for fine-scale genetic linkage
      mapping of the MEN2A locus.

PMID- 1346781
TI  - Thirty-one new RFLP systems detected by twenty-four DNA markers on human
      chromosome 10.
AB  - Thirty-one new RFLP systems corresponding to 24 loci have been identified from a
      chromosome 10-specific cosmid library. Twelve of the markers on the proximal long
      arm (cen-q11.2) of this chromosome, including four RFLP systems for the RET
      locus, will be especially useful in efforts to identify the gene responsible for
      multiple endocrine neoplasia type 2A (MEN2A). The new panel of markers also may
      contribute to fine-scale mapping of tumor suppressor genes associated with
      glioblastoma multiforme or renal cell carcinoma, because allelic deletions in
      these tumors have implied the presence of a tumor suppressor gene(s) on
      chromosome 10.

PMID- 1346782
TI  - A malic enzyme probe detects cross-hybridizing sequences closely linked to loci
      encoding other metabolic enzymes.
AB  - The cytoplasmic malic enzyme (Mod-1) catalyzes the oxidative decarboxylation of
      malate: malate + NADP+----pyruvate + CO2 + NADPH + H+. Using a cDNA clone of Mod
      1 as a probe, two new DNA markers not at the Mod-1 locus (restriction fragment
      length polymorphisms, RFLP) were detected by Southern blot analysis that showed
      extensive homology to Mod-1 sequences. Linkage of each restriction fragment
      length polymorphism to loci other than Mod-1 was assessed using the BXD (C57BL/6J
      x DBA/2J) recombinant inbred strains and confirmed by backcrosses. One
      polymorphic site, designated D9Rti1, was found to be closely linked to the
      phosphoglucomutase (Pgm-3) locus on Chromosome 9. The other hybridization site,
      designated D1Rti2, was closely linked to the isocitrate dehydrogenase (Idh-1)
      locus on Chromosome 1. The data presented imply that Mod-1 homologous sequences
      are tightly linked to three different metabolic enzymes.

PMID- 1346783
TI  - Genome sequencing conference. III: Evolution and progress.

PMID- 1346784
TI  - Determination of whether tomato spotted wilt virus replicates in Toxorhynchites
      amboinensis mosquitoes and the relatedness of this virus to phleboviruses (family
      Bunyaviridae).
AB  - Tomato spotted wilt virus (TSWV) has been reported to be morphologically,
      molecularly and structurally similar to viruses in the family Bunyaviridae. By
      various types of enzyme-linked immunosorbent assays (ELISA) and Western blot
      hybridizations, we tested TSWV with antibodies to 12 viruses in the Phlebovirus
      genus of this family. Serological relatedness was not found between TSWV and
      phleboviruses. However, one preparation of antibody to Arumowot virus reacted
      with a 53-kD protein from healthy plant extracts. Six-day-old adult
      Toxorhynchites amboinensis mosquitoes were inoculated with purified TSWV.
      Infectious virus was not detected in any of the injected insects during the 5
      week test period. However, TSWV antigens were detected in these mosquitoes by
      ELISA at the original injected level for at least a week after injection. TSWV
      antigen concentration began to decrease thereafter, but remained at detectable
      levels for as long as 5 weeks after injection. However, there was no evidence
      that TSWV replicated in mosquitoes.

PMID- 1346785
TI  - Coordinated leading- and lagging-strand synthesis at the Escherichia coli DNA
      replication fork. IV. Reconstitution of an asymmetric, dimeric DNA polymerase III
      holoenzyme.
AB  - Individually purified subunits have been used to reconstitute the action of the
      Escherichia coli DNA polymerase III holoenzyme (Pol III HE) at a replication fork
      formed in the presence of the primosome, the single-stranded DNA binding protein,
      and a tailed form II DNA template. Complete activity, indistinguishable from that
      of the intact DNA Pol III HE, could be reproduced with a combination of the DNA
      polymerase III core (Pol III core), the gamma.delta complex, and the beta
      subunit. Experiments where the Pol III core in reaction mixtures containing
      active replication forks was diluted suggested that the lagging-strand Pol III
      core remained associated continuously with the replication fork through multiple
      cycles of Okazaki fragment synthesis. Since the lagging-strand Pol III core must
      dissociate from the 3' end of the completed Okazaki fragment, this suggests that
      its association with the fork is via protein-protein interactions, lending
      credence to the idea that it forms a dimeric complex with the leading-strand Pol
      III core. An asymmetry in the action of the subunits was revealed under
      conditions (high ionic strength) that were presumably destabilizing to the
      integrity of the replication fork. Under these conditions, tau acted to stimulate
      DNA synthesis only when the primase was present (i.e. when lagging-strand DNA
      synthesis was ongoing). This stimulation was reflected by an inhibition of the
      formation of small Okazaki fragments, suggesting that, within the context of the
      model developed to account for the temporal order of steps during a cycle of
      Okazaki fragment synthesis, the presence of tau accelerated the transit of the
      lagging-strand Pol III core from the 3' end of the completed Okazaki fragment to
      the 3' end of the new primer.

PMID- 1346787
TI  - Somatostatin inhibits the activity of adenylate cyclase in cultured human
      meningioma cells and stimulates their growth.
AB  - It has been reported previously that most human meningiomas have receptors for
      somatostatin. Here we report the results of investigations of the effect of
      somatostatin and the somatostatin analog octreotide on the growth in vitro of
      human meningioma cells. Neither somatostatin nor its analog showed a direct
      growth inhibitory action on cultured human meningioma cells. Rather, there was a
      slight but significant stimulation of growth in the presence of somatostatin. The
      somatostatin receptors in meningioma tissue were shown to be functional since
      somatostatin inhibited forskolin-stimulated formation of cAMP by meningioma
      membranes. In addition, cAMP inhibited the growth of cultured meningioma cells.
      We conclude that the stimulation by somatostatin of the growth of human
      meningioma cells in vitro is caused by its inhibitory effect on cAMP formation.
      These results suggest that therapeutic trials of patients with (recurrent)
      inoperable meningiomas with somatostatin analogs have to be carried out with
      great caution.

PMID- 1346786
TI  - Antigen-receptor complex stimulation triggers protein kinase C-dependent
      CD11a/CD18-cytoskeleton association in T lymphocytes.
AB  - Although it is well accepted that intercellular adhesion involving the CD11a/CD18
      (LFA-1) complex is critical in a wide array of T cell-dependent processes, recent
      demonstrations of an LFA-1 high avidity state, induced by triggering the T cell
      receptor (TCR) complex, has raised questions about the intracellular signals
      generated and molecular events leading to effective cell coupling, as well as
      their orderly sequence. In this study, we assessed the effects of T cell
      activation on the actin-based cytoskeleton, and LFA-1, as well as their
      interaction. Crosslinking the TCR complex with anti-CD3 mAb resulted in actin
      polymerization and colocalization with LFA-1, as detected by fluorescence
      microscopy. This association was confirmed by immunoprecipitating LFA-1 from the
      detergent insoluble, cytoskeletal-associated membrane fraction after TCR
      crosslinking. These consequences were inhibited by the protein kinase C (PKC)
      inhibitor staurosporine or by PKC desensitization, as was a transient CD11a
      hyperphosphorylation, induced by monoclonal anti-CD3. Furthermore, a small
      percentage of beta 2-deficient T cells maintained the ability to rearrange the
      cytoskeleton in response to TCR complex activation, with F-actin-VLA4
      colocalization. These results provide evidence that the important consequences of
      TCR-induced signal transduction include a PKC-dependent cytoskeletal
      rearrangement, involving an association between leukocyte integrins and F-actin.
      We discuss the implications of these findings with respect to effective T cell
      functions.

PMID- 1346788
TI  - Effects of the dopamine agonist CV 205-502 in human prolactinomas resistant to
      bromocriptine.
AB  - In 21 patients with prolactinomas resistant to bromocriptine, we studied the
      effects of CV 205-502 on PRL hypersecretion and tumor mass, as assessed by
      consecutive computed tomography examinations. Cell culture studies were performed
      in 9 of such tumors. In 11 patients (group I; 52%) with a mean baseline plasma
      PRL level of 468 +/- 160 micrograms/L (+/- SE), normal PRL values were achieved
      after 1-6 months of treatment with 0.1-0.5 mg/day CV 205-502. Tumor size was
      reduced by 25% or more in 6 of 11 patients. In group II (n = 10), PRL levels (948
      +/- 538 micrograms/L at baseline) were reduced by 48% after treatment with 0.1
      mg/day CV 205-502. A progressive increase in the daily dose up to 0.5 mg did not
      further improve the partial reduction of PRL. No reduction in tumor size was
      observed in this group. The cell culture studies showed that 1) a brief exposure
      to both drugs provoked PRL suppression lasting 3 days; 2) in group I, CV 205-502
      suppressed PRL release more efficiently than bromocriptine, with a maximal
      inhibition of 72% at 10(-9) mol/L; and 3) in group II, CV 205-502 only achieved a
      26% inhibition of PRL release at 10(-8) mol/L, superimposable to that of
      bromocriptine. These data indicate that in at least half of such adenomas
      resistant to bromocriptine, CV 205-502, probably due to its higher affinity
      toward the D2 dopamine receptor, can overcome such resistance.

PMID- 1346789
TI  - c-erbB-2 overexpression and histological type of in situ and invasive breast
      carcinoma.
AB  - AIMS: To assess c-erbB-2 immunostaining in relation to morphological type of in
      situ and invasive breast carcinoma. METHODS: Formalin fixed, wax embedded
      archival tissue was used. Invasive carcinomas comprised 50 infiltrating ductal
      (NOS); seven medullary, 10 tubular, 15 mucinous and 24 classic invasive lobular.
      In situ carcinomas comprised 48 ductal (DCIS) and 10 cases of lobular (LCIS). The
      antibodies used were pAB1 (polyclonal) which stains cell lines that over express
      the c-erbB-2 oncogene, and ICR 12 (monoclonal) which stains sections of breast
      carcinoma known to show c-erbB-2 amplification. RESULTS: Immunostaining
      consistent with c-erbB-2 overexpression was found in 10 out of 50 cases of
      infiltrating ductal carcinoma (NOS), one of 24 infiltrating lobular carcinomas
      and one of seven medullary carcinomas only. Seventy per cent of ICR 12 positive
      cases of infiltrating ductal carcinoma also had extratumoral DCIS. Forty six per
      cent of pure DCIS lesions also showed strong membrane staining for c-erbB-2
      protein, confined to large cell types. CONCLUSIONS: Immunostaining for c-erb B-2
      oncoprotein occurs mainly in large cell DCIS and infiltrating ductal carcinoma
      NOS, especially those with an extratumoral DCIS component. There is a low
      incidence in other types of breast cancer, including those associated with a
      better prognosis. Different biological mechanisms may be responsible for
      histologically distinct types of breast carcinoma.

PMID- 1346790
TI  - Comparative effects of dopaminergic agonists on cardiovascular, renal, and renin
      angiotensin systems in hypertensive patients.
AB  - The role of dopaminergic receptors on renal function has been extensively
      studied. Recently dopaminergic receptor has been classified in two subtypes D1
      and D2, which seem to have different modulatory function. However, the role of
      dopaminergic receptors on cardiovascular function and more specifically the
      potential role of dopaminergic agonists as antihypertensive agents has not yet
      been clarified. Nine outpatients with mild and moderate hypertension were studied
      in the Cardiology Service of Vargas Hospital with a D1 agonist, piribedil, at 50
      100 mg/day, orally, for 8 weeks, and with a D2 agonist, bromocriptine, at 2.5 - 5
      mg/day, orally, for an another 8 weeks by using a placebo comparative crossover
      design. Piribedil reduced blood pressure with a modest increase in heart rate,
      plasma renin activity, and of plasma aldosterone, and an important increment of
      renal function. Bromocriptine reduced blood pressure with a decrease in heart
      rate and plasma aldosterone without altering renal function. There was no
      orthostatic hypotension with either agent. The authors conclude that activation
      of dopaminergic D1 receptor induces a vasodilatory and antihypertensive effect
      with a reflex increase in sympathetic tone, whereas activation of dopaminergic D2
      receptor induces a decrease in sympathetic tone, probably due to a decrease in
      norepinephrine release at adrenergic endings. The potential effect of these
      compounds as antihypertensive agents is of great interest because blood pressure
      reduction can be induced by a new mechanism, i.e. activation of dopaminergic
      receptors which results in a decrease of the renin angiotensin system or a
      vasodilatory action.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346791
TI  - Epanolol as a model for assessing patient preference in anti-anginal drug
      therapy.
AB  - Since drug therapy of angina is likely to produce a similar degree of efficacy
      for most drugs in common use, treatment choice should additionally focus on other
      factors, notably adverse events, quality of life, and convenience. Improvements
      in these factors can also lead to better compliance and can aid the doctor by
      cutting down the number of patient visits required to optimize therapy. The
      authors have evaluated the patient's overall assessment of symptomatic relief and
      adverse experiences in a comparative manner by means of the two-period crossover
      design using the patient's declared treatment preference as the primary
      measurement. This encapsulates several factors in a single assessment that can be
      understood by both physician and patient. The authors carried out two such
      studies of epanolol (Visacor), a novel anti-anginal agent with both beta-1
      selective antagonist activity and also beta-1 selective partial agonist activity.
      In one study (n = 608) the comparator was metoprolol, and in the other (n = 571)
      it was nifedipine. This article describes and evaluates the methodology of these
      studies. To assess preference optimally, each patient had to receive both
      treatments in short but clinically relevant treatment periods, with no washout.
      Re-entry into the second period, after withdrawal from the first, was permitted.
      Both studies showed advantages for epanolol, more marked in the case of
      nifedipine, arising from equivalent efficacy but fewer adverse events.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1346792
TI  - Localization of GABA, glycine, glutamate and tyrosine hydroxylase in the human
      retina.
AB  - A light microscope study using postembedding immunocytochemistry techniques to
      demonstrate the common neurotransmitter candidates gamma-aminobutyric acid
      (GABA), glycine, glutamate, and tyrosine hydroxylase for dopamine has been done
      on human retina. By using an antiserum to GABA, we found GABA-immunoreactivity
      (GABA-IR) to be primarily in amacrine cells lying in the inner nuclear layer
      (INL) or displaced to the ganglion cell layer (GCL). A few stained cells in the
      INL, which are probably interplexiform cells, were observed to project thin
      processes towards the outer plexiform layer (OPL). There were heavily stained
      bands of immunoreactivity in strata 1, 3 and 5 of the inner plexiform layer
      (IPL). An occasional ganglion cell was also GABA-IR. By using an antiserum to
      glycine, stained cells were observed at all levels of the INL. Most of these were
      amacrines, but a few bipolar cells were also glycine-IR. Displaced amacrine cells
      and large-bodied cells, which are probably ganglion cells, stained in the GCL.
      The bipolar cells that stained appeared to include both diffuse and midget
      varieties. The AII amacrine cell of the rod pathway was clearly stained in our
      material but at a lower intensity than two other amacrine cell types tentatively
      identified as A8 and A3 or A4. Again, there was stratified staining in the IPL,
      with strata 2 and 4 being most immunoreactive. An antiserum to glutamate revealed
      that most of the neurons of the vertical pathways in the human retina were
      glutamate-IR. Rod and cone photoreceptor synaptic endings labeled as did the
      majority of bipolar and ganglion cells. The rod photoreceptor stained more
      heavily than the cone photoreceptor in our material. While both midget and
      diffuse cone bipolar cell types were clearly glutamate-IR, rod bipolars were not
      noticeably stained. The most strongly staining glutamate-IR processes of the IPL
      lay in the outer half, in sublamina a. The antiserum to tyrosine hydroxylase
      (TOH) revealed two different amacrine cell types. Strongly immunoreactive cells
      (TOH1) had their cell bodies in the INL and their dendrites ramified in a dense
      plexus in stratum 1 of the IPL. Fine processes arising from their cell bodies or
      from the stratum 1 plexus passed through the INL to reach the OPL but did not
      produce long-ranging ramifications therein. The less immunoreactive amacrines
      (TOH2) lay in the INL, the center of the IPL or the GCL and emitted thick
      dendrites that were monostratified in stratum 3 of the IPL.

PMID- 1346793
TI  - Salmeterol, a new inhaled beta 2-adrenergic agonist, has a longer blocking effect
      than albuterol on hyperventilation-induced bronchoconstriction.
AB  - The duration of the blocking effect of salmeterol (50 micrograms), albuterol (200
      micrograms), and a placebo were compared in a double-blind study in 12 adult
      subjects with asthma who underwent hyperventilation tests with cold dry air (-20
      degrees C) on 4 study days. On the first day, the hyperventilation test was
      performed at various time intervals (baseline, 1, 4, 6, 8, 12, and 24 hours) with
      spontaneous functional recovery between each test to determine the within-day
      within-subject variability of the response. The response was assessed by
      interpolating the dose of cold dry air causing a 20% fall in FEV1. On the 3
      remaining days, separated by an interval of at least 5 days, the active or
      placebo medication was administered after spontaneous recovery from the first
      hyperventilation test. Spirometry was assessed 15 minutes and 1 hour later. The
      hyperventilation test was then performed and repeated 4 hours after
      administration of the drug. The test was repeated 6, 8, 12, and 24 hours later to
      detect any significant blocking effect. The improvement in FEV1 15 minutes and 1
      hour after the drug was administered was 19.8% and 20.4%, as compared to baseline
      for albuterol, and 16.3% and 16.8% for salmeterol (not significant). The mean
      duration of the blocking effect was 0.25 hour for the placebo, 3.5 hours for
      albuterol, and 15.9 hours for salmeterol (F = 24.5; p less than 0.001; Newman
      Keul's test was significant for every contrast). Eight of the 12 subjects still
      demonstrated some blocking effect 8 hours after taking salmeterol; this was true
      for only one subject receiving albuterol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346794
TI  - A comparative study in atopic subjects with asthma of the effects of salmeterol
      and salbutamol on allergen-induced bronchoconstriction, increase in airway
      reactivity, and increase in urinary leukotriene E4 excretion.
AB  - Salmeterol (SM) is a novel beta 2-adrenoceptor agonist with a duration of action
      in excess of 12 hours. Evidence from in vitro studies has also demonstrated that,
      unlike the short-acting beta 2-agonists, such as salbutamol (SB), it may have
      some anti-inflammatory properties. With a randomized, double-blind, crossover
      design, we have compared the inhibitory effects of SM (50 micrograms) and SB (200
      micrograms) delivered by metered-dose inhaler on allergen-induced
      bronchoconstriction, changes in airway reactivity, and urinary leukotriene (LT)
      E4 excretion in 12 atopic subjects with mild asthma. The immediate
      bronchoconstriction to allergen was significantly reduced by both beta 2-agonists
      (p less than 0.005), when reduction was expressed either in terms of maximum fall
      in FEV1 at 15 minutes after allergen (percent fall in FEV1, mean +/- SEM: 6.2 +/-
      4.9, SM; 5.7 +/- 2.5, SB; 40.4 +/- 6.3, placebo) or the area under the FEV1 time
      curve (AUC) for the first 120 minutes after allergen. Four hours after challenge,
      results in the SB-treated and placebo-treated groups were not significantly
      different and demonstrated a small persistent bronchoconstriction compared to
      bronchodilatation in the SM-treated group (percent fall in FEV1, respectively,
      9.3 +/- 3.7, 14.3 +/- 7.1, and -6.3 +/- 2.7; p less than 0.005, SM versus SB; p
      less than 0.02, SM versus placebo). Expressed in terms of AUC, only SM
      significantly reduced bronchoconstriction in the period 120 to 240 minutes after
      allergen (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346795
TI  - Genetic analysis using DNA polymorphism of the linkage between chromosome 11q13
      and atopy and bronchial hyperresponsiveness to methacholine.
AB  - Previous studies have suggested that there is a genetic predisposition for the
      development of asthma and atopy. A recent study has also demonstrated that there
      is a striking link between chromosome 11q and the IgE response underlying asthma
      and rhinitis. To assess the linkage between chromosome 11q (region D11S97) and
      atopy or bronchial hyperresponsiveness (BH), we have studied nine families of two
      and, in many instances, three generations with the index case having asthma
      and/or atopy. With variable number of tandem repeat analysis with the probe, p
      lambda-MS.51, we have been unable to confirm a significant link between region
      D11S97 of chromosome 11q and either atopy or BH to methacholine. We have
      demonstrated that atopy and BH produce similar log of odds scores with linkage
      analysis at each recombination fraction from 0.001 to 0.5 with both Hinf1 and
      Taq1 restriction digests and that the use of either a positive skin prick test or
      positive RAST as a definition of atopy does not significantly alter the log of
      odds score.

PMID- 1346796
TI  - Response of human natural killer (NK) cells to NK cell stimulatory factor (NKSF):
      cytolytic activity and proliferation of NK cells are differentially regulated by
      NKSF.
AB  - Natural killer cell stimulatory factor (NKSF) is a 70-kD heterodimeric cytokine
      that was initially isolated from conditioned medium of human B lymphoblastoid
      cell lines. The effects of recombinant NKSF on the function of human peripheral
      blood NK cells were examined. NKSF directly augmented the cytolytic activity of
      freshly isolated NK cells. Both CD56dim and CD56bright NK cells demonstrated
      enhanced cytotoxicity after brief exposure to NKSF. In contrast, highly purified
      T lymphocytes did not exhibit major histocompatibility complex-unrestricted
      cytotoxicity after short-term culture with NKSF. Like interleukin 2 (IL-2), NKSF
      augmented the lysis of NK-sensitive, NK-resistant, and antibody-coated targets.
      Both NKSF and IL-2 induced marked upregulation of several NK cell adhesion
      molecules known to participate in cytolysis, including CD2, CD11a, and CD54.
      However, NKSF activates NK cells through a pathway distinct from that of IL-2,
      since the presence of anti-IL-2 receptor (anti-IL-2R) antibodies or IL-4 did not
      inhibit the effects of NKSF. NKSF by itself induced very little proliferation of
      resting NK cells. NK cells preactivated in vitro with IL-2 demonstrated enhanced
      proliferation to NKSF, but the degree of proliferation was always inferior to
      that induced by IL-2 alone. Moreover, NKSF strongly inhibited IL-2-induced
      proliferation of either resting or preactivated NK cells. This inhibition was not
      the result of decreased IL-2R expression, because NKSF-activated NK cells
      expressed higher levels of both IL-2Rs p75 and p55. Furthermore, NKSF did not
      inhibit the proliferation of mitogen-activated T cells, indicating a selective
      effect on NK cell proliferation. Human NK cells expanded in vivo by prolonged
      continuous infusions of IL-2 remained fully responsive to NKSF. Picomolar
      concentrations of NKSF were as effective as nanomolar concentrations of IL-2 in
      augmenting the cytolytic activity of NK cells expanded in vivo by IL-2. NKSF may
      play an important role in the regulation of human NK cell function, and its
      possible use as a therapeutic cytokine deserves further investigation.

PMID- 1346798
TI  - Mapping of the nu gene using congenic nude strains and in situ hybridization.
AB  - The chromosomal location of the nu gene, which is responsible for hairlessness
      and athymus, was determined using six DNA markers (interleukin 3 [Il-3], Myhs,
      Acrb, Evi-2, Mpo, and Hox-2) on mouse chromosome 11. We constructed the high
      resolution physical mapping of the six DNA markers on chromosome 11 by in situ
      hybridization using fluorescence-labeled cosmid probes. The results indicate the
      order of centromere-(41cM)-Il-3-(3cM)-Myhs- (4cM)-Acrb-(6cM)-Evi-2-(3cM)-Mpo
      (5cM)- Hox-2. We have used congenic nude strains and examined which of the six
      DNA markers were derived from the original nude mouse. We found the Evi-2 locus
      is linked to the nu gene in all the informative, independent congenic nude
      strains. From these data, we could estimate the location of the nu gene, not only
      genetically but also physically within a region that spans approximately 17
      megabases (9 cM) between the Acrb and Mpo genes.

PMID- 1346797
TI  - Natural killer (NK) cell stimulatory factor increases the cytotoxic activity of
      NK cells from both healthy donors and human immunodeficiency virus-infected
      patients.
AB  - Natural killer cell stimulatory factor (NKSF), or interleukin 12 (IL-12), is a
      heterodimeric lymphokine produced by B cells that has multiple effects on T and
      NK cell functions. NKSF at concentrations as low as 0.4 pM enhances the
      spontaneous cytotoxic activity of peripheral blood lymphocytes (PBL) against a
      variety of tumor-derived target cell lines and virus-infected target cells. The
      combined treatment of PBL with NKSF and IL-2 results in a less than additive
      enhancement of cytotoxicity. NKSF enhances the cytotoxic activity of
      spontaneously cytotoxic CD16+CD5- NK cells and does not confer cytotoxic activity
      to CD16-CD5+ T cells. PBL from patients infected with human immunodeficiency
      virus (HIV) have significantly lower cytotoxic activity against tumor-derived
      target cells and virus-infected target cells than PBL from control healthy
      donors. Treatment of PBL from HIV-infected patients with NKSF and/or IL-2 results
      in an increase of NK cell cytotoxicity against both types of target cells to
      levels similar to or higher than those of untreated PBL from healthy donors. PBL
      from HIV-infected patients produce interferon gamma in response to NKSF and/or IL
      2, although at levels 5- or 10-fold lower than those produced by PBL from healthy
      donors. The multiple biological effects of NKSF, its activity at very low molar
      concentrations, and its ability to synergize with other physiological stimuli
      suggest that NKSF/IL-12 is a lymphokine likely to have physiological importance
      and considerable therapeutic potential.

PMID- 1346799
TI  - The purine analogs--a therapeutic beauty contest.

PMID- 1346800
TI  - 2-Chlorodeoxyadenosine produces a high rate of complete hematologic remission in
      relapsed acute myeloid leukemia.
AB  - PURPOSE: The purine analog 2-chlorodeoxyadenosine (2-CDA) was well tolerated and
      showed promising anti-leukemic activity in a phase I trial conducted at St Jude
      Children's Research Hospital. To substantiate and extend this result, we
      performed a phase II trial in a representative group of children and young adults
      with relapsed acute leukemia. PATIENTS AND METHODS: Twenty-four patients (median
      age, 11 years) with acute myeloid or lymphoid leukemia in first or later relapse
      (acute myeloid leukemia [AML], 17; acute lymphoid leukemia [ALL], seven) were
      given continuous infusion 2-CDA for 5 days at 8.9 mg/m2/d. Patients with residual
      blast cells 10 days after treatment received a second course of 2-CDA that was
      identical to the first. Detailed pharmacokinetic studies were performed on plasma
      collected from five patients. RESULTS: Eight (47%) of the 17 patients with AML
      had complete hematologic remissions (four after the initial course of 2-CDA), and
      two (12%) had partial remissions, for a total response rate of 59%. Only one
      child with ALL achieved remission. Seven of the responding patients underwent
      allogeneic or autologous bone marrow transplantation, with six remaining free of
      leukemia for a median of 7 months (range, 1 to 11 months). The major form of drug
      induced toxicity was hematologic, with severe neutropenia and thrombocytopenia
      (National Cancer Institute [NCI] grade 3 or 4) developing in 34 of the 36 courses
      of 2-CDA. In responding patients, the median times to recovery of neutrophil
      counts greater than 0.5 x 10(9)/L and platelet counts greater than 50 x 10(9)/L
      were 18 and 21 days, respectively. There were no deaths due to toxicity. The mean
      steady-state plasma concentration of 2-CDA was 34.6 nmol/L (range, 20 to 54
      nmol/L). CONCLUSION: 2-CDA given by prolonged continuous infusion has clinically
      significant activity against AML and merits further testing in multidrug regimens
      for this disease.

PMID- 1346801
TI  - 2-Chlorodeoxyadenosine treatment of low-grade lymphomas.
AB  - PURPOSE: Because of the need to identify effective new agents in the treatment of
      non-Hodgkin's lymphoma and because of the high activity of the purine analog 2
      chlorodeoxyadenosine (2-CdA) against chronic lymphocytic leukemia and hairy cell
      leukemia, a phase II trial of 2-CdA was initiated in patients with low-grade
      lymphocytic lymphomas. PATIENTS AND METHODS: Forty patients with low-grade
      lymphocytic lymphomas including diffuse small lymphocytic, follicular small
      cleaved, and follicular mixed histologies were enrolled onto the study.
      Conventional therapies had failed in all patients, and six patients had lymph
      node biopsies showing evidence of histologic evolution to a higher-grade
      lymphoma. A total of 107 courses of 2-CdA were administered. There were 27 males
      and 13 females. The median age was 59 years (range, 37 to 80 years). Patients had
      received a median of three prior therapies (range, one to six therapies).
      RESULTS: An overall response rate of 43% was achieved, with eight patients
      experiencing complete responses (CRs) and nine patients experiencing partial
      responses (PRs). The duration of responses ranged from 1 to greater than 33
      months without maintenance therapy (median duration of response, 5 months).
      Histology and prior therapy history did not seem to correlate with responses.
      Significant toxicity was limited to bone marrow suppression; 18% of patients
      developed neutropenia, and 30% developed thrombocytopenia. CONCLUSIONS: This
      phase II trial demonstrates that 2-CdA is an effective antilymphocyte,
      antineoplastic agent with significant activity as a single agent in patients with
      recurrent or refractory low-grade lymphocytic lymphoma. Responses were achieved
      with an acceptable toxicity profile. Further trials of this agent in previously
      untreated patients and in combination regimens are indicated and will be
      developed.

PMID- 1346802
TI  - beta-Amyloid peptides destabilize calcium homeostasis and render human cortical
      neurons vulnerable to excitotoxicity.
AB  - In Alzheimer's disease (AD), abnormal accumulations of beta-amyloid are present
      in the brain and degenerating neurons exhibit cytoskeletal aberrations
      (neurofibrillary tangles). Roles for beta-amyloid in the neuronal degeneration of
      AD have been suggested based on recent data obtained in rodent studies
      demonstrating neurotoxic actions of beta-amyloid. However, the cellular mechanism
      of action of beta-amyloid is unknown, and there is no direct information
      concerning the biological activity of beta-amyloid in human neurons. We now
      report on experiments in human cerebral cortical cell cultures that tested the
      hypothesis that beta-amyloid can destabilize neuronal calcium regulation and
      render neurons more vulnerable to environmental stimuli that elevate
      intracellular calcium levels. Synthetic beta-amyloid peptides (beta APs)
      corresponding to amino acids 1-38 or 25-35 of the beta-amyloid protein enhanced
      glutamate neurotoxicity in cortical cultures, while a peptide with a scrambled
      sequence was without effect. beta APs alone had no effect on neuronal survival
      during a 4 d exposure period. beta APs enhanced both kainate and NMDA
      neurotoxicity, indicating that the effect was not specific for a particular
      subtype of glutamate receptor. The effects of beta APs on excitatory amino acid
      (EAA)-induced neuronal degeneration were concentration dependent and required
      prolonged (days) exposures. The beta APs also rendered neurons more vulnerable to
      calcium ionophore neurotoxicity, indicating that beta APs compromised the ability
      of the neurons to reduce intracellular calcium levels to normal limits. Direct
      measurements of intracellular calcium levels demonstrated that beta APs elevated
      rest levels of calcium and enhanced calcium responses to EAAs and calcium
      ionophore. The neurotoxicity caused by EAAs and potentiated by beta APs was
      dependent upon calcium influx since it did not occur in calcium-deficient culture
      medium. Finally, the beta APs made neurons more vulnerable to neurofibrillary
      tangle-like antigenic changes induced by EAAs or calcium ionophore (i.e.,
      increased staining with tau and ubiquitin antibodies). Taken together, these data
      suggest that beta-amyloid destabilizes neuronal calcium homeostasis and thereby
      renders neurons more vulnerable to environmental insults.

PMID- 1346803
TI  - Dynorphin increases extracellular levels of excitatory amino acids in the brain
      through a non-opioid mechanism.
AB  - Administration of dynorphin A-(1-17) (Dyn 1-17), through a microdialysis probe
      stereotaxically placed into rat hippocampus, caused marked increases in the
      extracellular levels of glutamate and aspartate. The degree and duration of
      elevation of these excitatory amino acids (EAA) induced by Dyn 1-17 were dose
      dependent but were not modified by the centrally active opioid receptor
      antagonist nalmefene. At comparable doses, Dyn 2-17, which is inactive at the
      opioid receptor, produced similar alterations in EAA as Dyn 1-17, whereas Dyn 1-8
      caused significantly smaller changes of glutamate. Dynorphin and EAAs have each
      been implicated as pathophysiological factors in brain or spinal cord injuries,
      with dynorphin's actions shown to involve both opioid and non-opioid components.
      The present observations indicate a direct potential linkage between dynorphin
      and excitotoxin mechanisms of CNS injury and provide further support for the
      concept that dynorphin's pathophysiologic effects may include non-opioid actions
      of this peptide.

PMID- 1346804
TI  - Opioids excite dopamine neurons by hyperpolarization of local interneurons.
AB  - Increased activity of dopamine-containing neurons in the ventral tegmental area
      is necessary for the reinforcing effects of opioids and other abused drugs.
      Intracellular recordings from these cells in slices of rat brain in vitro showed
      that opioids do not affect the principal (dopamine-containing) neurons but
      hyperpolarize secondary (GABA-containing) interneurons. Experiments with agonists
      and antagonists selective for opioid receptor subtypes indicated that the
      hyperpolarization of secondary cells involved the mu-receptor. Most principal
      cells showed spontaneous bicuculline-sensitive synaptic potentials when the
      extracellular potassium concentration was increased from 2.5 to 6.5 or 10.5 mM;
      these were prevented by TTX and assumed to result from action potentials arising
      in slightly depolarized local interneurons. The frequency of these synaptic
      potentials, but not their amplitudes, was reduced by opioids selective for mu
      receptors. It is concluded that hyperpolarization of the interneurons by opioids
      reduces the spontaneous GABA-mediated synaptic input to the dopamine cells. In
      vivo, this would lead to excitation of the dopamine cells by disinhibition, which
      would be expected to contribute to the positive reinforcement seen with mu
      receptor agonists such as morphine and heroin.

PMID- 1346805
TI  - Modulatory effects of FMRF-NH2 on outward currents and oscillatory activity in
      heart interneurons of the medicinal leech.
AB  - Using single-electrode voltage clamp, heart interneurons of the medicinal leech
      were shown to possess both a rapidly inactivating outward current, IA, and a more
      slowly inactivating outward current, IK. IA and IK could be separated by their
      voltage sensitivity and kinetic properties. FMRF-NH2 (Phe-Met-Arg-Phe-NH2)
      modulates IK by shifting both steady state activation and inactivation to more
      hyperpolarized potentials, but it does not affect the time constants. IA and IK
      appear to use K+ as a charge carrier; a change in the external [K+] produced a
      shift in the apparent reversal potential in the direction predicted with
      potassium as the charge carrier. Both IA and IK are sensitive to
      tetraethylammonium (TEA) and 4-aminopyridine (4-AP), and TEA and 4-AP both
      interfere with the effects of FMRF-NH2 on IK. The biophysical properties of IA
      and of IK in the presence and absence of FMRF-NH2 were incorporated into a
      Hodgkin-Huxley model of these currents that could reproduce voltage-clamp data.
      FMRF-NH2 produces two apparently dissimilar effects on the heartbeat rhythm-
      acceleration and disruption. We suggest that both effects could result from the
      hyperpolarizing shifts in steady state activation and inactivation of IK.

PMID- 1346807
TI  - The effect of zidovudine treatment on serum neopterin and beta 2-microglobulin
      levels in mildly symptomatic, HIV type 1 seropositive individuals.
AB  - Sixty-one subjects with mildly symptomatic human immunodeficiency virus (HIV)
      infection were included in a double-blind, randomized, placebo-controlled trial
      of zidovudine (part of AIDS Clinical Trials Group protocol 016, ACTG 016) to
      evaluate changes in the serum immune activation markers neopterin and beta 2
      microglobulin (beta 2M) as early markers of the antiviral effect of zidovudine on
      HIV type 1 (HIV-1) infection. The mean values of serum neopterin and beta 2M
      levels in 27 placebo-treated subjects tended to increase with time. The mean
      value of neopterin in 34 subjects receiving zidovudine decreased at 4 weeks
      (15.76 nmol/L before treatment to 12.73 nmol/L, p = 0.001). The maximum reduction
      was seen at 8 weeks of treatment (10.78 nmol/L, p less than 0.0001).
      Subsequently, the mean value of serum neopterin increased but remained below the
      pretreatment value for more than a year. Serum beta 2M levels decreased (from
      3.01 to 2.69 mg/L at 4 weeks, p = 0.01) and reached the lowest level at 8 weeks
      (2.45 mg/L, p = 0.0002) in zidovudine recipients. The mean beta 2M level returned
      to pretreatment value at approximately 24 weeks of the treatment. There was a
      close correlation between changes from baseline in serum neopterin and beta 2M
      during the first 16 weeks of the zidovudine therapy, but not later. Subjects with
      greater reductions of serum neopterin or beta 2M tended to maintain lower levels
      of these markers with continued zidovudine administration.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1346806
TI  - NMDA channel behavior depends on agonist affinity.
AB  - We have compared the kinetic properties of NMDA receptor channels activated by
      exogenous agonists with those activated synaptically. Short (4 msec) applications
      of L-glutamate to outside-out patches from hippocampal neurons evoked currents
      that decayed with a double exponential time course that was controlled by both
      the unbinding rate of agonist and receptor desensitization. Lower-affinity
      agonists evoked NMDA receptor-activated currents that had faster rates of decay
      and recovered from desensitization more quickly, consistent with the idea that
      agonists which dissociate faster allow the receptor to reach a desensitized state
      less often. Both synaptic and patch responses could be well fitted with a simple
      kinetic model comprised of two independent but identical binding sites, one open
      state, one closed state, and one desensitized state, all doubly liganded.
      Provided that the agonist has a slow unbinding rate relative to the rates into
      the open and desensitized states (e.g., L-glutamate), this model predicts a
      response with two decay phases and can thus account for the synaptic response.
      Since the unbinding rate is the critical determinant of the time course,
      different affinity transmitters would affect such properties as excitatory
      postsynaptic current (EPSC) duration. Of the known endogenous excitatory amino
      acids, only L-glutamate has an affinity for the NMDA receptor consistent with the
      time course of the EPSC recorded between hippocampal neurons in culture.

PMID- 1346808
TI  - Prevalence of HIV-1, HIV-2, and HTLV-I/II in Spanish seamen.

PMID- 1346809
TI  - Sexual transmission of HTLV infections in southern India.

PMID- 1346810
TI  - Position paper on trauma care systems. Third National Injury Control Conference
      April 22-25, 1991, Denver, Colorado.

PMID- 1346811
TI  - Position paper on acute care treatment. Third National Injury Control Conference
      April 22-25, 1991, Denver, Colorado.

PMID- 1346812
TI  - A 37-year-old with amyl nitrite-induced methemoglobinemia.

PMID- 1346813
TI  - Acquired methemoglobinemia from amyl nitrate inhalation.

PMID- 1346814
TI  - [Chronic inflammatory intestinal disease and nephritis].
AB  - An 11 year old CD-patient developed an interstitial nephritis and acute kidney
      failure following treatment with Mesalazine (5-ASA) and Salazosulfapyridine
      (SASP). After removal of the medication and treatment with hemofiltration and
      prednisone there was only an incomplete recovery of the renal function
      (creatinine-clearance 34 ml/1,73 m2/min). It is thought that an hyperergic
      allergic reaction due to SASP and 5-ASA causes interstitial nephritis in
      inflammatory bowel disease (IBD). This reaction can be induced by re-exposition
      too. On the other hand IBD can be associated with glomerulonephritis. This could
      be a not very well known extraintestinal manifestation in IBD caused by immune
      complexes in serum and glomerula. A rapid histological verification of the renal
      disease is necessary for successful treatment. In both renal manifestations
      chronic courses are possible. These observations should not lead to avoid SASP/5
      ASA in treatment of IBD, but renal function should be routinely investigated.

PMID- 1346815
TI  - Prophylactic antibiotics prevent bacterial biofilm graft infection.
AB  - Bacterial biofilm graft infection is due to prostheses colonization by
      Staphylococcus epidermidis, a pathogen frequently recovered from perigraft
      tissues of man during vascular procedures despite the use of asepsis and
      prophylactic antibiotics. The effect of preoperative intraperitoneal cefazolin,
      administered at a standard (15 or 30 mg/kg) and high (120 mg/kg) dose, on the
      prevention of bacterial biofilm infection was studied in a rat model. Seventy
      four Dacron grafts, colonized in vitro with S. epidermidis to produce an adherent
      biofilm (3.19 +/- 0.71 x 10(7) colony-forming units/cm2 graft), were implanted in
      the dorsal subcutaneous tissue at 0.5, 2, and 4 hr after antibiotic
      administration. The study strain was a slime-producing clinical isolate with
      minimum inhibitory concentration (MIC) of 15-30 micrograms/ml to cefazolin.
      Subcutaneous tissue antibiotic levels were determined at each time interval. One
      week after implantation, the concentration of bacteria in the surface biofilm by
      quantitative agar culture was significantly decreased (P less than 0.05) only for
      grafts implanted when antibiotic tissue levels were greater than or equal to the
      MIC of the study strain. The result of no growth by biofilm broth culture was
      significantly achieved (P less than 0.01) only for grafts implanted 0.5 hr after
      high dose cefazolin, in which the tissue antibiotic level was above the MIC of
      the study strain. Antibiotics can markedly reduce the bacteria concentration of a
      prosthetic surface biofilm. The effectiveness of prophylactic antibiotics on the
      prevention of graft infection is dependent upon maintaining an adequate
      antibiotic level in the perigraft tissues for the duration of the procedure.

PMID- 1346816
TI  - [New antidotes for poisoning and mustard gas exposure are being introduced].

PMID- 1346817
TI  - Comparison of subcutaneous low-molecular-weight heparin with intravenous standard
      heparin in proximal deep-vein thrombosis.
AB  - In view of the potential of low-molecular-weight heparins (LMWH) to simplify
      initial therapy and allow outpatient treatment of proximal deep-vein thrombosis,
      we undertook a randomised comparison of fixed-dose subcutaneous LMWH with
      adjusted-dose intravenous standard heparin in the initial treatment of this
      disorder. Our main objectives were to compare the efficacy of these regimens for
      6 months of follow-up and to assess the risk of clinically important bleeding. Of
      170 consecutive symptomatic patients with venographically proven proximal deep
      venous thrombosis, 85 received standard heparin (to achieve an activated partial
      thromboplastin time of 1.5 to 2.0 times the pretreatment value) and 85 LMWH
      (adjusted only for body weight) for 10 days. Oral coumarin was started on day 7
      and continued for at least 3 months. The frequency of recurrent venous
      thromboembolism diagnosed objectively did not differ significantly between the
      standard-heparin and LMWH groups (12 [14%] vs 6 [7%]; difference 7% [95%
      confidence interval -3% to 15%]; p = 0.13). Clinically important bleeding was
      infrequent in both groups (3.5% for standard heparin vs 1.1% for LMWH; p greater
      than 0.2). We conclude that fixed-dose subcutaneous LMWH is at least as effective
      and safe as intravenous adjusted-dose heparin in the initial treatment of
      symptomatic proximal-vein thrombosis. Since there is no need for laboratory
      monitoring with the LMWH regimen, patients with venous thrombosis can be treated
      at home.

PMID- 1346818
TI  - Immunoprophylactic trial with combined Mycobacterium leprae/BCG vaccine against
      leprosy: preliminary results.
AB  - In an attempt to find a vaccine that gives greater and more consistent protection
      against leprosy than BCG vaccine, we compared BCG with and without killed
      Mycobacterium leprae in Venezuela. Close contacts of prevalent leprosy cases were
      selected as the trial population since they are at greatest risk of leprosy.
      Since 1983, 29,113 contacts have been randomly allocated vaccination with BCG
      alone or BCG plus 6 x 10(8) irradiated, autoclaved M leprae purified from the
      tissues of infected armadillos. We excluded contacts with signs of leprosy at
      screening and a proportion of those whose skin-test responses to M leprae soluble
      antigen (MLSA) were 10 mm or more (positive reactions). By July, 1991, 59
      postvaccination cases of leprosy had been confirmed in 150,026 person-years of
      follow-up through annual clinical examinations of the trial population (31 BCG,
      28 BCG/M leprae). In the subgroup for which we thought an effect of vaccination
      was most likely (onset more than a year after vaccination, negative MLSA skin
      test response before vaccination), leprosy developed in 11 BCG recipients and 9
      BCG/M leprae recipients; there were 18% fewer cases (upper 95% confidence limit
      [CL] 70%) in the BCG/M leprae than in the BCG alone group. For all cases with
      onset more than a year after vaccination irrespective of MLSA reaction the
      relative efficacy was 0% (upper 95% CL 54%; 15 cases in each vaccine group).
      Retrospective analysis of data on the number of BCG scars found on each contact
      screened suggested that BCG alone confers substantial protection against leprosy
      (vaccine efficacy 56%, 95% CL 27-74%) and there was a suggestion that several
      doses of BCG offered additional protection. There is no evidence in the first 5
      years of follow-up of this trial that BCG plus M leprae offers substantially
      better protection against leprosy than does BCG alone, but the confidence
      interval on the relative efficacy estimate is wide.

PMID- 1346819
TI  - Antiphospholipid antibodies after myocardial infarction and their relation to
      mortality, reinfarction, and non-haemorrhagic stroke.
AB  - Antiphospholipid antibodies have been suggested as markers for a high risk of
      recurrent cardiovascular events in young survivors of an acute myocardial
      infarction. However, there are few data to confirm or refute this hypothesis. In
      a cohort study, we have measured anticephalin (aCEPHA) and anticardiolipin (aCL)
      antibodies in a group of patients surviving an acute infarct. Of 597 patients
      studied, 13.2% were IgG or IgM aCEPHA positive compared with 4.4% of a reference
      population (n = 158; p = 0.002). In a multivariate analysis, adjusted for major
      cardiovascular risk factors, neither aCEPHA (IgG or IgM) nor a CL (IgG or IgM)
      was an independent risk factor for mortality, reinfarction, or non-haemorrhagic
      stroke. Although an increased proportion of survivors of a myocardial infarction
      have antiphospholipid antibodies, the presence of such antibodies is not a risk
      factor for subsequent coronary or cerebrovascular thrombosis.

PMID- 1346820
TI  - Stridor and focal laryngeal dystonia.
AB  - Fibreoptic laryngoscopy in 6 patients with laryngeal stridor showed immobile
      vocal cords in a paramedian position but no other local cause. Thus a diagnosis
      of Gerhardt's syndrome, usually ascribed to paralysis of vocal-cord abductor
      muscles, was made in 3 patients who had no other signs or symptoms of dystonia,
      and in 3 patients who had multifocal dystonia. Electromyography (EMG) showed
      evidence of overactivity of vocal-cord adductors, with no evidence of denervation
      in the abductor muscles. Botulinum toxin injection of the overactive
      thyroarytenoid muscles abolished stridor. These clinical and EMG findings
      indicate that Gerhardt's syndrome is not caused by paralysis of vocal-cord
      abductors, but represents a focal laryngeal dystonia which may be treatable by
      botulinum toxin injections of vocal-cord adductor muscles rather than by
      arytenoidopexy or tracheostomy.

PMID- 1346822
TI  - Transfection of the pharmacopoeia: intramuscular gene therapy.

PMID- 1346821
TI  - Response of peripheral-blood mononuclear cells to glutamate decarboxylase in
      insulin-dependent diabetes.
AB  - Insulin-dependent diabetes is characterised by autoantibodies to several
      pancreatic-islet-cell antigens, including glutamate decarboxylase. We measured
      the proliferative responses to this antigen of peripheral-blood mononuclear cells
      from patients with newly diagnosed insulin-dependent diabetes, relatives of
      diabetic patients, and healthy controls. The likelihood of a positive response
      was substantially greater among the diabetic patients and relatives positive for
      islet-cell autoantibodies (ICA) than among subjects at low risk of diabetes
      (controls and ICA-negative relatives). Glutamate decarboxylase may have a
      pathogenetic role in insulin-dependent diabetes.

PMID- 1346823
TI  - Bettering BCG.

PMID- 1346824
TI  - New bone?

PMID- 1346825
TI  - Adenosine and the diagnosis of tachycardias.

PMID- 1346826
TI  - Scientific perspectives on adult respiratory distress syndrome.

PMID- 1346827
TI  - Management of adult respiratory distress syndrome.

PMID- 1346828
TI  - Investigation of patients with stroke and transient ischaemic attacks.

PMID- 1346830
TI  - Bielarus: political fallout from Chernobyl.

PMID- 1346829
TI  - Safe Motherhood Initiative: getting our priorities straight.

PMID- 1346831
TI  - A decade of AIDS research.

PMID- 1346832
TI  - Eosinophilia associated with clozapine.

PMID- 1346833
TI  - Wrong lesson from Finnish trial of cardiovascular disease prevention.

PMID- 1346834
TI  - Flumazenil-induced psychotic disorder in hepatic encephalopathy.

PMID- 1346835
TI  - DNA adducts and exposure to burning oil.

PMID- 1346836
TI  - Evolution, transposons, and malignant disease.

PMID- 1346837
TI  - Ondansetron for patients given abdominal radiotherapy.

PMID- 1346838
TI  - Ondansetron in intractable nausea and vomiting.

PMID- 1346839
TI  - Is fever really a "side-effect" of biological response modifiers?

PMID- 1346840
TI  - Polyarteritis nodosa and parvovirus B19 infection.

PMID- 1346841
TI  - Lack of effect of somatostatin and analogues in lymphorrhagia from ruptured
      thoracic duct.

PMID- 1346842
TI  - Cyanate derived from urea in uraemia.

PMID- 1346843
TI  - Latex allergy in patient with allergy to fruit.

PMID- 1346844
TI  - Latex allergy in patient with allergy to fruit.

PMID- 1346845
TI  - Selective screening for neuroblastoma in high-risk population.

PMID- 1346846
TI  - Anaphylactic shock induced by intravenous gadopentetate dimeglumine.

PMID- 1346847
TI  - Counting birds, bees, and NCDs.

PMID- 1346848
TI  - Chirality and drug development.

PMID- 1346849
TI  - Continuous non-invasive assessment of pulsus paradoxus.

PMID- 1346850
TI  - Successful use of monoclonal anti-lipid-A IgM in infant with meningococcal
      sepsis.

PMID- 1346851
TI  - Restoration of hypoglycaemia awareness by human recombinant growth hormone.

PMID- 1346852
TI  - Striatal dopamine D2-receptor blockade by typical and atypical neuroleptics.

PMID- 1346853
TI  - Ethics, clinical research, and clinical practice in obstetric anaesthesia.

PMID- 1346854
TI  - Return to Pakistan of pipenzolate plus phenobarbitone.

PMID- 1346855
TI  - Patient referral and NHS reforms.

PMID- 1346856
TI  - Regulation of assay kits.

PMID- 1346857
TI  - The Italian way of osteoporosis.

PMID- 1346858
TI  - Day care for hypertension in pregnancy.

PMID- 1346859
TI  - Trichuris trichiura infection and mental development in children.

PMID- 1346860
TI  - Snuff and recurring pulmonary infiltrations in chronic renal failure.

PMID- 1346861
TI  - Foscarnet for CMV retinitis.

PMID- 1346862
TI  - Laparoscopically assisted vaginal hysterectomy.

PMID- 1346863
TI  - Need for second-generation anti-HCV testing in haemophilia.

PMID- 1346864
TI  - History of previous drug misuse in HCV-positive blood donors.

PMID- 1346865
TI  - Overexpression of p53 gene in head-and-neck cancer, linked with heavy smoking and
      drinking.

PMID- 1346866
TI  - Renal allograft rejection and antibodies to epithelial cells.

PMID- 1346867
TI  - Relieving the pain of pressure sores.

PMID- 1346868
TI  - Choice between inactivated and oral poliovirus vaccines in India.

PMID- 1346869
TI  - Serious intercurrent disease in healthy volunteers in clinical pharmacological
      research.

PMID- 1346870
TI  - Dependence and oestrogen replacement.

PMID- 1346871
TI  - Dependence and oestrogen replacement.

PMID- 1346872
TI  - Dependence and oestrogen replacement.

PMID- 1346873
TI  - Dependence and oestrogen replacement.

PMID- 1346875
TI  - Infectious agent for Kaposi's?

PMID- 1346874
TI  - Norharman, a normal body constituent.

PMID- 1346876
TI  - Immunogenicity of combined diphtheria, tetanus, and pertussis vaccine given at 2,
      3, and 4 months versus 3, 5, and 9 months of age.
AB  - In the UK an accelerated schedule for immunisation against diphtheria, tetanus,
      and pertussis (injections at 2, 3, and 4 months of age) was introduced in 1990 to
      replace the more widely spaced schedule of 3, 5, and 9 months. There is concern,
      however, that the new schedule may be less immunogenic and therefore less
      protective than the old schedule. We have measured serum concentrations of
      antibodies against diphtheria, pertussis, and tetanus in infants immunised
      according to the two regimens. Both schedules resulted in protective
      concentrations of antibody against tetanus and diphtheria and in satisfactory
      antibody responses to three pertussis antigens (filamentous haemagglutinin,
      pertussis toxin, fimbriae). However, immunisation by the old schedule led to
      significantly higher antibody concentrations against both diphtheria and tetanus
      than did immunisation by the new schedule (p less than 0.01). In infants
      immunised with the new schedule, postimmunisation antibody concentrations against
      tetanus toxoid and against two pertussis antigens (pertussis toxin and fimbriae)
      were significantly lower in infants in whom preimmunisation (maternally derived)
      antibody concentrations were high (p less than 0.02). The findings suggest that
      with an accelerated immunisation schedule maternal antibodies can have an
      inhibitory effect on the responses to immunisation against tetanus and pertussis.

PMID- 1346877
TI  - Respiratory disease in very-low-birthweight infants after prenatal thyrotropin
      releasing hormone and glucocorticoid. TRH Study Group.
AB  - Although prenatal glucocorticoid treatment reduces neonatal respiratory
      morbidity, respiratory distress syndrome and chronic lung disease (CLD) develop
      in many very-low-birthweight infants despite therapy. To investigate the effect
      of additional prenatal treatment with thyrotropin-releasing hormone (TRH), we did
      a multicentre, blinded, randomised trial. 404 women with threatened preterm
      delivery at less than 32 weeks' gestation received betamethasone plus TRH (4
      doses of 400 micrograms 8-hourly) or betamethasone plus placebo. 103 infants who
      were fully treated and of less than 1500 g birthweight were evaluated during the
      neonatal period. TRH treatment (55 infants) did not affect the total incidence of
      respiratory distress syndrome (47% vs 58% in controls) or of severe respiratory
      distress syndrome (13% vs 25% in controls, p = 0.11). CLD (defined as requirement
      for supplemental oxygen at 28 days after birth) developed in significantly fewer
      TRH-treated infants (18% vs 44% of controls, p less than 0.01). The unadjusted
      relative risk of CLD with TRH therapy was 0.40 (95% CI 0.26-0.80, p less than
      0.05), and this was not materially changed after adjustment for potentially
      modifying variables. There were significantly fewer adverse outcomes, defined as
      death or continuing oxygen requirement, in the TRH group than in the steroid
      alone group both at 28 days and when infants reached 36 weeks' postconceptional
      age. The incidence of other complications of prematurity was similar in the two
      groups. Prenatal TRH reduces the incidence of chronic lung disease among
      betamethasone-treated infants.

PMID- 1346878
TI  - HPV-16-related DNA sequences in Kaposi's sarcoma.
AB  - In the USA, Kaposi's sarcoma associated with the acquired immunodeficiency
      syndrome (AIDS-KS) is ten times more common in homosexual or bisexual men than in
      heterosexual men with AIDS. One explanation for this finding is that AIDS-KS may
      be caused by an infectious agent. Because there is a high incidence of human
      papillomavirus (HPV) infection, especially HPV-16, in homosexual men, we have
      sought HPV DNA sequences in Kaposi's sarcoma. We used the polymerase chain
      reaction with a primer pair specific for the highly conserved E6 region of HPV-16
      to detect HPV-16 homologous DNA fragments in tumour tissues from 97 patients with
      KS and in KS-derived cell cultures. HPV DNA sequences were found in 11 of 69 KS
      skin tumours from homosexual men with AIDS-KS, in 3 of 11 KS biopsy specimens
      from homosexual men who had no clinical or laboratory evidence of HIV-infection,
      and in 5 of 17 KS skin lesions from HIV-1-negative elderly men and women with
      classic KS. The same primer pair amplified HPV-16 homologous fragments from two
      different continuous cell cultures derived from pleural effusion fluid of
      patients with pulmonary AIDS-KS and two continuous cell cultures derived from KS
      skin lesions. The findings suggest that HPV-16-related DNA sequences are
      associated with different forms of KS and may have a role in the pathogenesis of
      this neoplasm.

PMID- 1346879
TI  - Clonal basis for resurgence of serious Streptococcus pyogenes disease in the
      1980s.
AB  - During the 1980s there was a resurgence of serious Streptococcus pyogenes
      infections with complications, including rheumatic fever, sepsis, severe soft
      tissue invasion, and toxic-shock-like syndrome (TSLS). We have investigated the
      suggested association between expression of a scarlet fever toxin, SPE A, and
      systemic toxicity, and the possibility that a new highly virulent clone of S
      pyogenes has emerged and spread world wide. We studied serotype M1 strains, the
      serotype most commonly associated with serious complications. 19 isolates from
      patients with sepsis, with or without TSLS, and 48 from patients with
      uncomplicated pharyngitis or superficial skin infection were subjected to
      restriction-enzyme digestion and electrophoresis; 56 isolates (19 serious, 37
      uncomplicated disease) were then examined by hybridisation to an speA gene probe.
      17 (90%) of the 19 serious-disease isolates had a characteristic ("invasive", I)
      restriction-fragment profile and were positive for the speA gene. Significantly
      lower proportions of the isolates from patients with uncomplicated disease had
      the I profile (21/48 [44%]; p = 0.0035) and speA (20/37 [54%]; p less than
      0.001). These findings suggest that the strains from patients with serious
      disease are a unique clone, which became the predominant cause of severe
      streptococcal infections in the United States and elsewhere in the late 1980s.

PMID- 1346881
TI  - Reversed cerebral asymmetry in women with breast cancer.
AB  - Altered intrauterine hormonal environment might predispose to both atypical
      cerebral asymmetry and breast cancer. We therefore investigated computed
      tomographic scans of 79 right-handed, white patients with breast cancer and 97
      controls to assess the pattern of cerebral asymmetry. Women with breast cancer
      had a reversed pattern of cerebral asymmetry significantly more often than did
      controls (p less than 0.0001 for both frontal and occipital width. Our findings
      suggest that an intrauterine or early life factor, probably hormonal, could
      predispose to breast cancer in adulthood.

PMID- 1346880
TI  - Intestinal epithelial cell protein phosphorylation in enteropathogenic
      Escherichia coli diarrhoea.
AB  - The ability of enteropathogenic Escherichia coli (EPEC) to cause diarrhoea in man
      is associated with the formation of characteristic histopathological lesions in
      small-intestine enterocytes, with gross cytoskeletal damage and loss of brush
      border microvilli. Investigation of enterocyte protein phosphorylation in
      response to EPEC infection showed that the major phosphorylated protein,
      identified by immunoprecipitation, is myosin light-chain--an important
      cytoskeletal protein known to affect actin organisation in non-muscle cells. High
      enterocyte concentrations of actin and myosin were observed at sites of bacterial
      infection. Our findings indicate that enterocyte cytoskeletal changes in response
      to EPEC may be directly triggered by bacterial adherence through signal
      transduction pathways that stimulate protein kinase activity.

PMID- 1346882
TI  - Chemoprophylaxis for infective endocarditis: faith, hope, and charity challenged.

PMID- 1346883
TI  - Pertussis: adults, infants, and herds.

PMID- 1346884
TI  - Antitachycardia devices.

PMID- 1346885
TI  - The heart in myotonic dystrophy.

PMID- 1346887
TI  - Pathophysiology of acute ischaemic stroke.

PMID- 1346886
TI  - Prospective multicentre study of pregnancy outcome after lithium exposure during
      first trimester.
AB  - Lithium carbonate is an effective drug for prophylaxis and treatment of major
      affective disorders. In-utero exposure to lithium during the first trimester of
      pregnancy might be associated with an increased risk of cardiac malformations,
      especially the rare Ebstein's anomaly. We prospectively recruited and followed
      148 women (mean age 30 years, SD 5 range 15-40) using lithium during the first
      trimester of pregnancy, who consulted four teratogen information centres in the
      USA and Canada. Pregnancy outcome was compared with that of controls matched for
      maternal age. We had complete follow-up of pregnancy outcome in 138 of 148
      patients recruited. In the other 10, fetal echocardiograms were available but
      postnatal follow-up was not done. Mean daily dose of lithium was 927 mg (SD 340).
      Rates of major congenital malformations did not differ between the lithium (2.8%)
      and control (2.4%) groups. 1 patient in the lithium group chose to terminate
      pregnancy after Ebstein's anomaly was detected by a prenatal echocardiogram.
      There was 1 ventricular septal defect in the controls. Birthweight was
      significantly higher in the lithium-exposed infants than in the controls despite
      identical gestational ages (3475 [660] g vs 3383 [566] g, p = 0.02). The true
      difference in birthweight might have been even larger, since significantly more
      women using lithium than controls were cigarette smokers (31.8% vs 15.5%, p =
      0.002). These results indicate that lithium is not an important human teratogen.
      Women with major affective disorders who wish to have children may continue
      lithium therapy, provided that adequate screening tests, including level II
      ultrasound and fetal echocardiography, are done.

PMID- 1346888
TI  - Medical treatment of acute ischaemic stroke.

PMID- 1346889
TI  - Immune surveillance, organophosphorus exposure, and lymphomagenesis.
AB  - Prevalence of lymphoproliferative disorders is increased in populations with
      various chemical exposures, including organophosphorus compounds. Lymphomas are
      also more common in individuals with a substantially decreased monocyte esterase
      activity. Organophosphorus compounds inhibit esterases associated with monocytes,
      natural killer (NK) cells, lymphokine-activated killer (LAK) cells, and cytotoxic
      T lymphocytes, and these inhibitory effects impair immune surveillance and
      cytotoxic functions mediated by such cells. Lymphoma development is also
      associated with Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6)
      infections, which are regulated by cytotoxic immune responses mediated by
      monocytes, T cells, and NK cells. My hypothesis is that lymphomagenesis is a
      multistep process, and the absence or inhibition of monocyte esterase and perhaps
      other immune cell esterases alters esterase-dependent detoxification of a factor
      critical for the early steps of oncogenesis. Also, such an enzyme deficit might
      impair the processes that regulate the dissemination and limit the total burden
      of pathogens such as the lymphoma-associated herpesviruses. An added risk to any
      viral-mediated lymphoproliferation might be an organophosphorus-induced oncogenic
      genetic change.

PMID- 1346890
TI  - Immunohistochemical detection of papillomavirus antigens in Kaposi's sarcoma.

PMID- 1346891
TI  - Thalidomide for systemic lupus erythematosus.

PMID- 1346892
TI  - Possible low-dose-aspirin-induced gastropathy.

PMID- 1346893
TI  - Gastric intramucosal pH in critically ill patients.

PMID- 1346894
TI  - HIV as target for zidovudine.

PMID- 1346895
TI  - HIV seropositivity in paid blood donors.

PMID- 1346896
TI  - Exposure to chemicals and development of malignant disease.

PMID- 1346897
TI  - Infection after subcutaneous interleukin-2.

PMID- 1346898
TI  - Hypersensitivity to Samsum ant.

PMID- 1346899
TI  - Human equivalent of canine acral lick.

PMID- 1346900
TI  - Iohexol to monitor GFR.

PMID- 1346901
TI  - Gestrinone in cyclical breast pain.

PMID- 1346902
TI  - Gestrinone in cyclical breast pain.

PMID- 1346903
TI  - Beware of symptomatic sickle-cell traits.

PMID- 1346904
TI  - Typhoid vaccine and laboratory indicators of clinical protection.

PMID- 1346905
TI  - Overseas training for doctors from developing countries.

PMID- 1346906
TI  - Overseas training for doctors from developing countries.

PMID- 1346907
TI  - Publicity and unpublished results.

PMID- 1346908
TI  - Acute pressure area care.

PMID- 1346909
TI  - Human rights in Sudan.

PMID- 1346910
TI  - Molecular elimination of the minimal residual Ph1 clone with IFN alpha in CML.

PMID- 1346911
TI  - Blindness associated with high-dose carboplatin.

PMID- 1346912
TI  - Uveitis after antineutrophil cytoplasmic antibody contamination of immunoglobulin
      replacement therapy.

PMID- 1346913
TI  - Type II collagen antibodies in patients with sensorineural hearing loss.

PMID- 1346914
TI  - Deafness after meningococcal meningitis.

PMID- 1346915
TI  - beta-Amyloid protein immunoreactivity in muscle of patients with inclusion-body
      myositis.

PMID- 1346916
TI  - Reduced plasma L-arginine in hypercholesterolaemia.

PMID- 1346917
TI  - The J-curve hypothesis.

PMID- 1346918
TI  - Does thrombolysis produce cholesterol embolisation?

PMID- 1346919
TI  - Fragmentation of pulmonary embolus.

PMID- 1346920
TI  - Competitive interactions at [3H]1,3-di(2-tolyl)guanidine (DTG)-defined sigma
      recognition sites in guinea pig brain.
AB  - In saturation binding experiments, (+)pentazocine, (+)3-(3-hydroxyphenyl)-N
      propylpiperidine (3-PPP), haloperidol and rimcazole did not inhibit the binding
      of [3H]DTG in a purely competitive fashion. Although Scatchard analysis indicated
      that [3H]DTG bound to a single site, the inhibition curves of some, but not all,
      reference compounds exhibited Hill coefficients of less than 0.8. The Scatchard
      data were consistent with a model of hyperbolic competitive inhibition of binding
      to the [3H]DTG-defined sigma site, although other possibilities such as negative
      cooperativity or binding to two sites cannot be definitively excluded. Compounds
      from numerous pharmacological and structural classes inhibited the binding of
      [3H]DTG, suggesting that interactions of [3H]DTG with other receptors may have
      confounded the Scatchard analysis of the binding of [3H]DTG to sigma recognition
      sites.

PMID- 1346921
TI  - Developmental biology. The making of the ear.

PMID- 1346922
TI  - Developmental defects of the ear, cranial nerves and hindbrain resulting from
      targeted disruption of the mouse homeobox gene Hox-1.6.
AB  - Gene targeting in mouse embryo-derived stem cells has been used to generate mice
      with a disruption in the homeobox gene Hox-1.6. Mice heterozygous at the Hox-1.6
      locus appear normal, whereas Hox-1.6-/Hox-1.6- mice die at or shortly after
      birth. These homozygotes exhibit profound defects in the formation of the
      external, middle and inner ears as well as in specific hindbrain nuclei, and in
      cranial nerves and ganglia. The affected tissues lie within a narrow region along
      the anteroposterior axis of the mouse but are of diverse embryonic origin. The
      set of defects associated with the disruption of Hox-1.6 is distinct from and
      nonoverlapping with that of the closely linked Hox-1.5 gene. But both mutations
      cause loss, rather than homeotic transformation, of tissues and structures.

PMID- 1346923
TI  - Expansion of an unstable DNA region and phenotypic variation in myotonic
      dystrophy.
AB  - Myotonic dystrophy is the commonest adult form of muscular dystrophy, with an
      estimated incidence of 1 per 7,500, although this is likely to be an
      underestimate because of the difficulty of detecting minimally affected
      individuals. It is a multisystem autosomal dominant disorder of unknown
      biochemical basis. No case of new mutation has been proven. We have isolated a
      human genomic clone that detects novel restriction fragments specific to
      individuals with myotonic dystrophy. A two-allele EcoRI polymorphism is seen in
      normal individuals, but in most affected individuals one of the normal alleles is
      replaced by a larger fragment, which varies in length both between unrelated
      affected individuals and within families. The unstable nature of this region may
      explain the characteristic variation in severity and age at onset of the disease.
      A second polymorphism at this locus is in almost complete linkage disequilibrium
      with myotonic dystrophy, strongly supporting our earlier results which indicated
      that most cases are descended from one original mutation.

PMID- 1346924
TI  - Detection of an unstable fragment of DNA specific to individuals with myotonic
      dystrophy.
AB  - Myotonic dystrophy (DM) is the most common form of adult muscular dystrophy, with
      a prevalence of 2-14 per 100,000 individuals. The disease is characterized by
      progressive muscle weakness and sustained muscle contraction, often with a wide
      range of accompanying symptoms. The age at onset and severity of the disease show
      extreme variation, both within and between families. Despite its clinical
      variability, this dominant condition segregates as a single locus at chromosome
      19q13.3 in every population studied. It is flanked by the tightly linked genetic
      markers ERCC1 proximally and D19S51 distally; these define the DM critical
      region. We report the isolation of an expressed sequence from this region which
      detects a DNA fragment that is larger in affected individuals than in normal
      siblings or unaffected controls. The size of this fragment varies between
      affected siblings, and increases in size through generations in parallel with
      increasing severity of the disease. We postulate that this unstable DNA sequence
      is the molecular feature that underlies DM.

PMID- 1346925
TI  - Cloning of the essential myotonic dystrophy region and mapping of the putative
      defect.
AB  - Myotonic dystrophy is a common dominant disorder (global incidence of 1:8,000)
      with variable onset and a protean nature of symptoms mainly involving progressive
      muscle wasting, myotonia and cataracts. To define the molecular defect, we have
      cloned the essential region of chromosome 19q13.3, including proximal and distal
      markers in a 700-kilobase contig formed by overlapping cosmids and yeast
      artificial chromosomes (YACs). The central part of the contig bridges an area of
      about 350 kilobases between two new flanking crossover borders. This segment has
      been extensively characterized through the isolation of five YAC clones and the
      subsequent subcloning in cosmids from which a detailed EcoRI, HindIII, MluI and
      NotI restriction map has been derived. Two genomic probes and two homologous
      complementary DNA probes were isolated using the cosmids. These probes are all
      situated within approximately 10 kilobases of genomic DNA and detect an unstable
      genomic segment in myotonic dystrophy patients. The length variation in this
      segment shows similarities to the instability seen at the fragile X locus. The
      physical map location and the genetic characteristics of the length polymorphism
      is compatible with a direct role in the pathogenesis of myotonic dystrophy.

PMID- 1346926
TI  - Selective inhibition of neurite outgrowth on mature astrocytes by Thy-1
      glycoprotein.
AB  - THY-1, the smallest member of the immunoglobulin superfamily, is a major cell
      surface component expressed by several tissues. The protein, carbohydrate and
      gene structures of this molecule are known, yet its function is not. It is highly
      expressed in nervous tissue, where it appears on virtually all neurons after the
      cessation of axonal growth. Here we show that expression of Thy-1 by a neural
      cell line inhibits neurite outgrowth on mature astrocytes, but not on other
      cellular substrata which include Schwann cells and embryonic glia. This
      inhibition of neurite extension on astrocytes can be reversed by low
      concentrations (nanomolar) of soluble Thy-1. If a similar interaction between
      neuronal Thy-1 and astrocytes occurs in vivo, it could stabilize neuronal
      connections and suppress axonal regrowth after injury in the astrocyte-rich areas
      of adult central nervous system.

PMID- 1346927
TI  - Mouse Small eye results from mutations in a paired-like homeobox-containing gene.

PMID- 1346928
TI  - High level transient gene expression in human lymphoid cells by SV40 large T
      antigen boost.
AB  - High level transient gene expression in lymphoid cells has always been
      challenging because of the difficulty to efficiently transfect such cells. This
      has precluded any attempt to clone cDNA encoding proteins by means of their
      specific biological function in lymphoid cells. We have developed a very
      efficient transient eukaryotic expression system analogous to the well-known
      expression system in COS cells. Firefly luciferase and human CD2 genes were used
      as reporter genes and cloned into the eukaryotic shuttle vector pCDM8 which
      contains the strong cytomegalovirus promoter and the SV40 origin of replication
      for autonomous plasmid replication in permissive host cells that express the
      large SV40 T Antigen. Co-transfection of the reporter plasmids together with an
      SV40 T Ag expressing plasmid resulted in the several fold amplification of either
      the Luc activity or the cell surface expression of the CD2 marker in a transient
      assay. The level of amplification was dependent on the strength of the promoter
      used to drive the SV40 T Ag expression and was correlated with the extent of
      autonomous replication of the reporter plasmid in transfected cells. This highly
      efficient transient gene expression by SV40 T Ag boost was suitable to several
      human cell lines, making this system of general interest for expression cloning
      strategies or other gene transfer application that need high level expression.

PMID- 1346929
TI  - Identification of a maize nucleic acid-binding protein (NBP) belonging to a
      family of nuclear-encoded chloroplast proteins.
AB  - A cDNA encoding a nuclear-encoded chloroplast nucleic acid-binding protein (NBP)
      has been isolated from maize. Identified as an in vitro DNA-binding activity, NBP
      belongs to a family of nuclear-encoded chloroplast proteins which share a common
      domain structure and are thought to be involved in posttranscriptional regulation
      of chloroplast gene expression. NBP contains an N-terminal chloroplast transit
      peptide, a highly acidic domain and a pair of ribonucleoprotein consensus
      sequence domains. NBP is expressed in a light-dependent, organ-specific manner
      which is consistent with its involvement in chloroplast biogenesis. The
      relationship of NBP to the other members of this protein family and their
      possible regulatory functions are discussed.

PMID- 1346931
TI  - p185c-neu and epidermal growth factor receptor associate into a structure
      composed of activated kinases.
AB  - The protein product of the neu protooncogene, p185c-neu, is structurally similar
      to the epidermal growth factor receptor (EGFR). Overexpression of these two
      receptor tyrosine kinases, but not either separately, leads to transformation and
      tumorigenicity. Heterodimerization of p185c-neu and EGFR occurs in M1 cells,
      which express both receptors. We have individually identified the two components
      of the heterodimer as EGFR and p185c-neu. Analysis of this association with
      relatively nondenaturing detergents and in the absence of cross-linkers indicates
      that noncovalent interactions are primarily responsible for heterodimer
      formation. The rapid reversible heterodimerization was promoted by EGF binding to
      its receptor. Functionally, the heterodimer is a highly active protein kinase for
      receptor autophosphorylation and exogenous substrate phosphorylation in vitro.
      The isolated heterodimer was highly phosphorylated on tyrosine residues in vivo.
      These results indicate that the physical association between EGFR and p185c-neu
      is of functional significance and define enzymatic features of complex receptor
      formation.

PMID- 1346930
TI  - Cardiostimulatory and antiarrhythmic activity of tubulin-binding agents.
AB  - Rhythmic, spontaneously pulsating cardiac cells cultured from newborn rats are
      immediately stimulated to beat faster by addition of a number of tubulin-binding
      agents but not by their non-tubulin-binding analogues. The tubulin-binding agents
      tested include vinblastine, vincristine, navelbine, two analogs of vinblastine
      (S12362 and S12363), nocodazole, colchicine, and podophylotoxin. In addition to
      binding tubulin, all of the above agents also depolymerize microtubules. In
      contrast, taxol, a tubulin-binding agent that stabilizes microtubules, does not
      stimulate cardiac cells. Moreover, the immediate and ensuing cardiac stimulation
      by vinblastine at 0.05 microgram/ml is completely blocked by pre- and cotreatment
      with taxol at 1.0 microgram/ml. The time necessary to reverse the
      cardiostimulatory effect of vinblastine is significantly longer than that
      required for nocodazole, further implicating depolymerization of microtubules in
      the cardiac activity of these agents. All of the tubulin-binding agents tested
      (including taxol) also immediately reverse adriamycin-induced arrhythmias. By
      using a monoclonal antibody to alpha-tubulin, typical filamentous microtubules
      are visualized in cardiac muscle and cocultured non-muscle cells by
      immunofluorescence. When cells are treated for 2 hr with vinblastine at 0.05
      microgram/ml, fluorescence is detected in cross-striated patterns in cardiac
      muscle cells. Overall, these data open the possibility of uncovering an
      additional relationship between cytoskeletal elements (other than actin and
      myosin) and the contractility of cardiac muscle. They also suggest an alternative
      mechanism for affecting cardiac cell function in vitro (namely, by tubulin
      binding agents). If these agents are shown to be cardioactive in vivo, they may
      provide another approach to the treatment and management of cardiac arrhythmias.

PMID- 1346932
TI  - T-cell immunity to the joining region of p210BCR-ABL protein.
AB  - The hallmark of chronic myelogenous leukemia is the translocation of the human c
      abl protooncogene (ABL) from chromosome 9 to the specific breakpoint cluster
      region (bcr) of the BCR gene on chromosome 22. The t(9;22)(q34;q11) translocation
      results in the formation of a BCR-ABL fusion gene that encodes a 210-kDa chimeric
      protein with abnormal tyrosine kinase activity. The ABL and BCR genes are
      expressed by normal cells and thus the encoded proteins are presumably
      nonimmunogenic. However, the joining-region segment of the p210BCR-ABL chimeric
      protein is composed of unique sequences of ABL amino acids joined to BCR amino
      acids that are expressed only by malignant cells. The current study demonstrates
      that the joining region of BCR-ABL protein is immunogenic to murine T cells.
      Immunization of mice with synthetic peptides corresponding to the joining region
      elicited peptide-specific, CD4+, class II major histocompatibility complex
      restricted T cells. The BCR-ABL peptide-specific T cells recognized only the
      combined sequence of BCR-ABL amino acids and not BCR or ABL amino acid sequences
      alone. Importantly, the BCR-ABL peptide-specific T cells could recognize and
      proliferate in response to p210BCR-ABL protein. The response of peptide-specific
      T cells to protein demonstrated that p210BCR-ABL can be processed by antigen
      presenting cells so that the joining segment is bound to class II major
      histocompatibility complex molecules in a configuration similar to that of the
      immunizing peptide and in a concentration high enough to stimulate the antigen
      specific T-cell receptor. Thus, BCR-ABL protein represents a potential tumor
      specific antigen related to the transforming event and shared by many individuals
      with chronic myelogenous leukemia.

PMID- 1346933
TI  - Global and local genome mapping in Arabidopsis thaliana by using recombinant
      inbred lines and random amplified polymorphic DNAs.
AB  - A population of Arabidopsis thaliana recombinant inbred lines was constructed and
      used to develop a high-density genetic linkage map containing 252 random
      amplified polymorphic DNA markers and 60 previously mapped restriction fragment
      length polymorphisms. Linkage groups were correlated to the classical genetic map
      by inclusion of nine phenotypic markers in the mapping cross. We also applied a
      technique for local mapping that allows targeting of markers to a selected genome
      region by pooling DNA from recombinant inbred lines based on their genotype. We
      conclude that random amplified polymorphic DNAs, used in conjunction with a
      recombinant inbred population, can facilitate the genetic and physical
      characterization of the Arabidopsis genome and that this method is generally
      applicable to other organisms for which appropriate populations either are
      available or can be developed.

PMID- 1346935
TI  - Neurohumoral regulation of the cerebral circulation.

PMID- 1346934
TI  - CD3 zeta dependence of the CD2 pathway of activation in T lymphocytes and natural
      killer cells.
AB  - In T lymphocytes, signal transduction through the CD2 adhesion molecule requires
      surface expression of the CD3-Ti T-cell receptor (TCR) complex. In contrast, in
      natural killer (NK) cells, CD2 functions in the absence of a TCR. Because the TCR
      on T lymphocytes and the CD16 low-affinity IgG Fc receptor (Fc gamma receptor
      type III) complex on NK cells share a common CD3 zeta subunit, we reasoned that
      CD3 zeta may be critical for CD2 signaling in T lymphocytes and NK cells. Here we
      show that transfection of a cDNA encoding a transmembrane form of CD16 into TCR-
      variants of the Jurkat T-cell line results in CD16 expression in association with
      endogenous CD3 zeta homodimers and restores CD2 signaling function. To test
      directly the role of CD3 zeta in CD2 triggering, we then transfected human CD2
      into each of two murine T-T hybridomas that express TCRs containing either a full
      length CD3 zeta subunit or a truncated CD3 zeta subunit incapable of transducing
      signals. Despite expression of equivalent surface levels of TCR, CD2-mediated
      signaling is seen only in the T cells containing wild-type CD3 zeta. These
      findings show that (i) CD16 on NK cells is functionally equivalent to the TCR on
      T lymphocytes for coupling CD2 to signaling pathways and (ii) CD2 signal
      transduction depends upon the CD3 zeta subunit of the TCR complex and, by
      inference, the CD3 zeta subunit of the CD16 complex.

PMID- 1346936
TI  - Role of insulin and glucagon in oxytocin effects on glucose metabolism.
AB  - Oxytocin (OT) infusion in normal dogs increases plasma insulin and glucagon
      levels and increases rates of glucose production and uptake. The purpose of this
      study was to determine whether the effects of OT on glucose metabolism were
      direct or indirect. The studies were carried out in normal, unanesthetized dogs
      in which OT infusion was superimposed on infusion of either somatostatin, which
      suppresses insulin and glucagon secretion, or clonidine, which suppresses insulin
      secretion only. Infusion of 0.2 microgram/kg/min of somatostatin suppressed basal
      levels of plasma insulin and glucagon and inhibited the OT-induced rise of these
      hormones by about 60-80% of that seen with OT alone. The rates of glucose
      production and uptake by tissues, measured with [6-3H] glucose, were
      significantly lower than those seen with OT alone, and the rise in glucose
      clearance was completely inhibited. Clonidine (30 micrograms/kg, sc), given along
      with an insulin infusion to replace basal levels of insulin, completely prevented
      the OT-induced rise in plasma insulin and markedly reduced the glucose uptake
      seen with OT alone, but did not reduce the usual increase in plasma glucose and
      glucagon levels or glucose production. To determine whether the OT-induced rise
      in plasma insulin was in response to the concomitant increase in plasma glucose,
      similar plasma glucose levels were established in normal dogs by a continuous
      infusion of glucose and an OT infusion was superimposed. OT did not raise plasma
      glucose levels further, but plasma insulin levels were increased, indicating that
      OT can stimulate insulin secretion independently of the plasma glucose changes.
      Studies by others have shown that the addition of OT to pancreatic islets or
      intact pancreas can stimulate insulin and glucagon secretion, indicating a direct
      effect. Our studies agree with that and suggest that in vivo, OT raises plasma
      insulin levels, at least in part, through a direct action on the pancreas. These
      studies also show that OT increases glucose production by increasing glucagon
      secretion and, in addition, a direct effect of OT on glucose production is
      likely. The OT-induced increase in glucose uptake is mediated largely by
      increased insulin secretion.

PMID- 1346938
TI  - Addictive states. 70th Annual Meeting of the Association for Research in Nervous
      and Mental Disease, November 30-December 1, 1990, New York City.

PMID- 1346937
TI  - Taurine uptake into chick B cells.
AB  - The objective of the present study was to determine whether chick B cells possess
      a specific transport system for taurine. The Bursa of Fabricius was isolated from
      newly hatched to 6-week-old chicks and an enriched fraction (86.2%) of B cells
      was isolated. The chick B cells maintained a high intracellular taurine
      concentration (0.8-1.12 mM) that decreased with age. The B cells exhibited
      carrier-mediated and simple diffusion uptake components, but only the carrier
      mediated component increased with age. Inhibitor studies indicated taurine uptake
      was sodium and energy dependent. The data demonstrate that chick B cells possess
      a specialized taurine transport system and the activity of this system changes
      during posthatch B cell development.

PMID- 1346940
TI  - [Practical problems in the long-term drug treatment of ischemic heart disease and
      hypertension].
AB  - In choosing drugs for treatment of ischemic heart disease or hypertension one has
      -next to effects on angina or blood pressure--to consider possible influences on
      long term course. A simple dosing-scheme with a low number of tablets as well as
      a thorough information of the patient about the prescribed medication are equally
      important for the therapeutic success.

PMID- 1346939
TI  - Rationale for maintenance pharmacotherapy of opiate dependence.
AB  - At this time, 27 years after the initial studies on development of methadone for
      the maintenance treatment of opiate addiction were begun, it has been shown that
      [table; see text] methadone meets most criteria for a pharmacologic agent for
      chronic treatment of an addiction. It is effective after oral dosing: it has a
      long biological half-life in humans, it causes minimal side effects when used in
      chronic treatment, and it has no true toxic effects or serious side effects. Also
      methadone has been shown to be very effective when appropriately used in programs
      which combine pharmacotherapy with the best elements of "drug free" treatment,
      that is, counseling and psychological support. In addition to pharmacological
      treatment, there should be access to, if not on-site, medical and behavioral care
      as needed, as well as linkage to resources for various aspects of rehabilitation.
      At this time many of the actions, as well as the specific sites of action, and
      mechanisms of actions of methadone as used in chronic treatment of opiate
      addiction have been defined by scientific experimentation, both at the
      preclinical and clinical levels. It is known that methadone prevents abstinence
      symptoms, prevents drug hunger or craving, blocks euphorogenic effects of other
      opiates, and prevents relapse to illicit use of opiates. It is known that the
      site of action of methadone is at specific opioid receptors. Research to date
      suggests that there is no demonstrable down-regulation or up-regulation of opioid
      receptors during chronic opioid agonist perfusion, although chronic
      administration of the opioid antagonist naltrexone does appear to up-regulate
      opioid receptors. Clinical studies show that chronic use of methadone allows
      normalization of release and peripheral levels of one of the classes of
      endogenous opioids, beta-endorphin, and the related peptides derived from POMC
      released and processed from the anterior pituitary in humans. Also levels of beta
      endorphin in cerebrospinal fluid become normal during chronic maintenance
      treatment, reflecting apparently normal processing and release of beta-endorphin
      at brain or hypothalamic sites of POMC production. Available data from studies of
      beta-endorphin indicate that there is a [table; see text] normalization, rather
      than disruption, of the endogenous opioid system in general during steady state
      administration of methadone, as contrasted with intermittent dosing and then
      abrupt withdrawal of short-acting opiates such as heroin. Although there is still
      much to be learned about the neurobiology of opiate addiction, at this time we do
      know a great deal about the effects of opiates and opioids.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1346941
TI  - Subtentorial subdural empyema: case report.
AB  - We present a case of an extensive subtentorial subdural empyema of
      otorhinological origin. Although 3%-6% of all intracranial suppurations are
      infratentorial, there is no report on extensive multiloculated subtentorial
      empyema so far.

PMID- 1346942
TI  - Compartmental distribution of cytochrome oxidase in the striatum of the rat.
AB  - Endogenous cytochrome oxidase activity was investigated in the adult rat striatum
      at the light microscope level to see if it was distributed in accordance with the
      established striatal patch/matrix compartmentalisation. Striatal sections stained
      to visualise cytochrome oxidase activity were compared with serial sections
      stained to visualise tyrosine hydroxylase and calbindinD28k-like
      immunoreactivity, established markers of the matrix compartment. The distribution
      of endogenous cytochrome oxidase activity was found to coincide with the
      immunocytochemical staining pattern seen for tyrosine hydroxylase and
      calbindinD28k whereby areas of intense tyrosine hydroxylase and calbindinD28k
      like immunoreactivity (termed the matrix) corresponded to areas of intense
      cytochrome oxidase activity. Conversely, areas of less intense tyrosine
      hydroxylase and calbindinD28k-like immunoreactivity (termed patches) corresponded
      to areas of low cytochrome oxidase activity. In addition, the distribution of two
      other oxidative enzymes involved in the regulation of mitochondrial respiration,
      succinic dehydrogenase and NADH-diaphorase, was examined in the striatum and
      substantia nigra by using histochemical techniques. Both NADH-diaphorase and
      succinic dehydrogenase histochemistry showed an uneven pattern of neuropil
      staining in the striatum. In the substantia nigra a few intensely stained cell
      bodies were seen in the dorsal-lateral tip of the pars reticulata with both
      histochemical techniques. By using an anti-cytochrome oxidase antibody an
      abundance of immunoreactive cell bodies and processes were seen in the substantia
      nigra, particularly in the dorso-medial rim and dorsal tip of the pars
      reticulata. The substantia nigra pars lateralis contained many intensely stained
      cytochrome oxidase-like immunoreactive cell bodies and processes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1346943
TI  - Electrophysiological profile of the new atypical neuroleptic, sertindole, on
      midbrain dopamine neurones in rats: acute and repeated treatment.
AB  - Sertindole (Lundbeck code No. Lu 23-174) (1-[2-[4-[5-chloro-1-(4-fluorophenyl)-1H
      indol-3-yl]-1-piperidinyl] ethyl]-2-imidazolidinone) is a new potential
      neuroleptic compound. After 3 weeks of treatment sertindole shows an extreme
      selectivity to inhibit the number of spontaneously active dopaminergic (DA)
      neurones in ventral tegmental area (VTA) while leaving the number of active DA
      neurones in substantia nigra pars compacta (SNC) unaffected. Acute injection of
      apomorphine or baclofen reverse the inhibition of activity seen after repeated
      treatment with sertindole. This suggests that sertindole induces a depolarization
      inactivation of the DA neurones. The depolarization inactivation is reversible
      since normal activity of DA neurones is found in both SNC and VTA after two weeks
      withdrawal from repeated treatment with a low dose with sertindole. One or two
      weeks administration of a high dose of sertindole induced only minor effects on
      the DA neurones in VTA; i.e., in order to obtain the depolarization inactivation
      sertindole requires 3 weeks of treatment as has also been reported for other
      neuroleptics. Three weeks of treatment with clozapine induces a selective
      inhibition of the active DA neurones in VTA but at much higher doses than seen
      with sertindole, while haloperidol induces a non-selective decrease of
      spontaneously active DA neurones in both areas. In acute electrophysiological
      experiments intravenous (i.v.) administration of sertindole--in contrast to both
      clozapine and haloperidol--neither reverse d-amphetamine- nor apomorphine-induced
      inhibition of the firing frequencies of DA neurones in SNC or in VTA. In
      addition, sertindole does not--even in high doses--increase the firing frequency
      of DA neurones in SNC or VTA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346944
TI  - Local application of bicuculline potentiates NMDA-receptor-mediated sensory
      responses of brain noradrenergic neurons.
AB  - Direct application of bicuculline methiodide (BIC) to noradrenergic locus
      coeruleus (LC) neurons potently enhanced their sensory responsiveness. This
      increased responsiveness was due to the long-lasting expression of a new, N
      methyl-D-aspartate (NMDA) receptor-mediated component of the synaptic response.
      This enhancement only occurred when a high stimulus intensity was used to induce
      the sensory response. A similar increase in responsiveness was observed with
      stimulation of the nucleus paragigantocellularis (PGi), one of the major direct
      afferents to LC. This action of BIC was neither mimicked by picrotoxin,
      penicillin, or the GABA-B antagonist, 2-hydroxy-baclofen, nor by agents that
      directly depolarize LC neurons. In addition, the inverse agonist of the
      benzodiazepine receptor, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3
      carboxylate (DMCM), did not mimic this effect of BIC. The BIC-potentiated
      response component was eliminated by direct application of the neurotransmitter
      gamma-aminobutyric acid (GABA). These results indicate that BIC, acting at a
      possibly novel site, unmasks NMDA receptors that can be activated by sensory
      stimuli. This may reflect a mechanism whereby interactions between two major
      neurotransmitter systems, excitatory amino acids (EAAs) and GABA, potently
      modulate signal transmission in the brain.

PMID- 1346945
TI  - Reduced tyrosine hydroxylase immunoreactivity in locus coeruleus of suicide
      victims.
AB  - Antibodies against tyrosine hydroxylase (TH, the rate-limiting enzyme in
      norepinephrine synthesis) and dopamine beta-hydroxylase (DBH, the last enzyme in
      the synthesis) were used for immunohistochemical staining of human brain locus
      coeruleus sections, obtained postmortem from suicide victims and matched
      controls. Stain density over individual cells was quantified by a computerized,
      video-camera-based image analysis system. Mean stain density for TH was
      significantly lower (by about 30%) in the locus coeruleus of suicide victims.
      There was no difference between suicides and controls in DBH immunoreactivity or
      in the number of TH immunoreactive cells. Reduced TH availability, either
      genetically or environmentally determined, may contribute to the noradrenergic
      insufficiency postulated to occur in depression and the increased beta-adrenergic
      receptor concentrations observed in prefrontal cortex of suicide victims.

PMID- 1346946
TI  - The current status of the Whipple operation for periampullary carcinoma.
AB  - In an address delivered before the Boston Surgical Society in 1942, Whipple made
      the following statement: The radical operation for these tumors of the ampullary
      region and pancreas, based on the principle of wide, en bloc removal of the
      tumors, as required in modern cancer surgery, is evidently in an evolutionary
      stage. Many more cases, with five-year survivals, will be required before valid
      claims can be made for the operations as done at present. In the nearly 50 years
      since this address, the Whipple operation has undergone numerous modifications
      and technical refinements. A number of recent clinical studies clearly
      demonstrate that this procedure now can be performed with acceptable morbidity
      and mortality, and that long-term survival is possible even for patients with
      adenocarcinoma of the head of the pancreas. The decline in operative morbidity
      and mortality has been achieved largely through advances in surgical technique.
      Further improvements in survival for patients with periampullary tumors are
      likely to occur through the development of more effective adjuvant therapy and
      improved understanding of the biologic behavior of these tumors.

PMID- 1346947
TI  - Assessment of QT dispersion in symptomatic patients with congenital long QT
      syndromes.
AB  - It has been suggested that QT dispersion recorded on the surface
      electrocardiogram may be a predictor of arrhythmic events in patients with
      congenital QT prolongation. To evaluate this, 9 patients (6 female, mean age 17.6
      years) with congenital long QT syndromes, all of whom had syncope and documented
      torsades de pointes, were studied. Patients were studied off treatment and during
      therapy with beta-blocking agents. Three patients were also studied after left
      stellate ganglionectomy. An age-matched control group was also studied. Good
      quality 12-lead electrocardiograms were recorded from all patients. For each
      lead, QT and RR intervals were measured, and QTc value was calculated. QT and QTc
      dispersions were calculated for each patient. Patients had a significantly longer
      mean QT interval compared with that of the control group (450 +/- 100 vs 359 +/-
      63 ms; p = 0.015) at similar mean RR intervals (736 +/- 231 vs 783 +/- 289 ms),
      with a longer mean QTc value (0.53 +/- 0.08 vs 0.41 +/- 0.02 s1/2; p = 0.004).
      Patients also had longer QT and QTc dispersions compared with those of the
      control group (110 +/- 45 vs 43 +/- 12 ms [p = 0.004], and 0.108 +/- 0.03 vs 0.05
      +/- 0.02 s1/2 [p = 0.002], respectively). QT and QTc dispersions on and off beta
      blocking agents were not significantly different. Comparing patients with
      frequent and those with infrequent symptoms, there was no difference in QT or QTc
      dispersion either off treatment or during therapy with beta-blocking
      agents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346948
TI  - Molecular characterization of hemoglobin C in Sicily.
AB  - Analysis of polymorphisms of the beta-globin gene cluster was performed on 12
      families and on one unrelated individual of Sicilian origin who carried
      hemoglobin C (Hb C). Two different haplotypes were found in association with beta
      c Sicilian alleles, corresponding to haplotypes I and II previously described in
      American blacks. In our population, the more frequent one (haplotype I) was
      linked to the lack of a polymorphic HpaI site 3' to the beta gene (13.0-kb
      fragment), similarly to haplotype I in blacks, while the less frequent one was
      linked to a 7.0-kb HpaI fragment attributable to a site that had never been
      previously described in linkage with beta c alleles. In Italy, these two
      haplotypes have been found in rare cases in association with beta A alleles.
      These findings provide new insights into the origin of Hb C present in Sicily,
      suggesting that (1) the beta c mutation detected in Sicily derived from African
      black chromosomes and does not represent a new mutation; and (2) Hb C may have
      originated either by multiple mutational events on separate chromosomes or by
      mutation in the HpaI site 3' to the beta gene in a pre-existing beta c
      chromosome.

PMID- 1346949
TI  - Serum prolactin levels in homosexual and bisexual men with HIV infection.
AB  - OBJECTIVE: Prolactin is a neurohormone that may be secreted in response to stress
      and also has regulatory effects on the immune system. Some, but not all, studies
      suggest that prolactin levels are higher than normal in persons with HIV
      infection. The authors measured prolactin levels in HIV-positive and HIV-negative
      homosexual and bisexual men to assess possible differences in levels and then
      examined relationships between prolactin level and measures of medical status,
      anxiety, depression, stress, and neuropsychological test performance. METHOD:
      Blood for prolactin level determination was obtained from 121 HIV-seropositive
      and 79 HIV-seronegative homosexual and bisexual men enrolled in a longitudinal
      study. The men also underwent a daylong assessment that included medical,
      immunological, psychiatric, psychosocial, psychosexual, and neuropsychological
      evaluations. RESULTS: There was no statistically significant difference in serum
      prolactin level among the seronegative men, the seropositive men with no or
      minimal physical symptoms, and the seropositive men with significant physical
      symptoms of HIV infection. Furthermore, within the HIV-seropositive group, the
      correlations between serum prolactin level and measures of depression, anxiety,
      stress, and neuropsychological test performance were all nonsignificant.
      CONCLUSIONS: Serum prolactin level does not seem to respond to HIV infection or
      to be related to stress or psychiatric symptoms in HIV-infected men. As none of
      the subjects had AIDS, the possibility cannot be ruled out that prolactin level
      increases in very late stages of HIV infection.

PMID- 1346950
TI  - Racial/ethnic identity and amount and type of psychiatric treatment.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship of
      racial/ethnic identity to the amount and type of psychiatric treatment received
      by white, black, Latino, and Asian patients in the Los Angeles County mental
      health system. METHOD: The patients studied (N = 19,400) consisted of all adult
      inpatients and outpatients seen in all county mental health facilities between
      January 1983 and August 1988. Multiple regression analysis was used to test the
      relationship between race/ethnicity and four measures of treatment received:
      number of treatment sessions, treatment modality, treatment setting, and
      therapist's discipline. The covariates included in the analyses were age, sex,
      socioeconomic status, primary language, diagnosis, and measures of treatment when
      these were logical predictors and were not acting as dependent variables.
      RESULTS: Race/ethnicity did not have a consistent significant relationship to the
      treatment variables studied. However, diagnosis had a consistent and highly
      significant relationship to all four measures of treatment. A psychotic diagnosis
      was related to receiving more treatment sessions, greater use of medication,
      greater use of inpatient treatment, and less treatment by a professional
      therapist. Socioeconomic status and primary language also had consistent and
      significant relationships to three of the treatment variables. CONCLUSIONS: In
      considering modifications to the service delivery system, clinicians must
      evaluate whether the type of treatment provided to psychotic patients is the
      treatment of choice in terms of effectiveness and efficiency or whether it
      involves bias in service delivery. Similarly, the issue of bias in treatment of
      lower socioeconomic patients must be addressed.

PMID- 1346951
TI  - Vitamin E in the treatment of tardive dyskinesia: a double-blind placebo
      controlled study.
AB  - The authors compared vitamin E with placebo in a double-blind randomized
      crossover study of 27 patients with tardive dyskinesia. Each treatment period
      lasted for 6 weeks. Vitamin E showed no differences from placebo in the treatment
      of tardive dyskinesia.

PMID- 1346952
TI  - Possible interaction between an MAOI and "ecstasy".

PMID- 1346953
TI  - [The effect of sufentanil on regional and global cerebral circulation and
      cerebral oxygen consumption in the dog].
AB  - The intracranial hemodynamic and metabolic effects of 20 micrograms/kg sufentanil
      were studied in ten mongrel dogs. Anesthesia was maintained with 0.7 vol.% end
      tidal isoflurane and 50% nitrous oxide in oxygen. Catheters were inserted into
      both femoral arteries and veins, the superior sagittal sinus, the left atrium,
      and the lateral cerebral ventricle for blood pressure measurement, arterial and
      sagittal sinus blood sampling, radioactive microsphere injections, and
      intracranial pressure (ICP) monitoring. Cardiac output (CO) was measured using an
      electromagnetic flow probe on the pulmonary artery. Following baseline
      measurements, sufentanil was injected and data were recorded at 5, 15, and 30
      min. RESULTS. In group 1 (n = 5) blood pressure was not controlled, while in
      group 2 (n = 5) blood pressure was maintained at baseline level with a
      phenylephrine infusion. Arterial blood pressure decreased by 32% in response to
      sufentanil in group 1 and remained constant in group 2 according to the protocol.
      CO decreased by 40%-50% in both groups. Regional and global cerebral blood flow
      (CBF) decreased by 25%-40% with no difference between groups. The cerebral
      hemodynamic changes were associated with a decrease of 35%-40% in cerebral oxygen
      consumption. ICP did not change over time. DISCUSSION. These data are in contrast
      to studies in dogs, where sufentanil produced non-dose-dependent increases in CBF
      and ICP. Our results are more consistent with studies in humans and rats where
      administration of sufentanil was associated with either no change or decreases in
      cerebral hemodynamics, metabolism, and ICP. We conclude that in dogs with normal
      intracranial physiology sufentanil decreases regional and global CBF in response
      to a decrease in cerebral metabolic demand without significantly affecting ICP.

PMID- 1346954
TI  - Fatal rodenticide poisoning with brodifacoum.
AB  - The increased prevalence of rodents resistant to warfarin led to the development
      of the hydroxycoumarin anticoagulant brodifacoum. A 25-year-old man attempted
      suicide by consuming four boxes of d-CON Mouse-Prufe II; each box contains 42 g
      of bait that is 0.005% brodifacoum. He presented to a hospital nine days later
      with syncope, hematochezia, gross hematuria, epistaxis, anemia, and a severe
      coagulopathy. Radiographic studies were consistent with pleural, pericardial, and
      mediastinal hemorrhages. Vitamin K and fresh frozen plasma were given, and he was
      later discharged on oral phytonadione (vitamin K1). The patient's coagulopathy
      recurred, necessitating multiple plasma transfusions and prolonged treatment with
      oral phytonadione. Fifteen weeks after hospital discharge, he presented again
      with a history of additional brodifacoum ingestion. Neurologic status was
      initially normal, but in the emergency department he suddenly became comatose
      soon after emesis was induced with syrup of ipecac. Computed tomography of the
      brain revealed a subarachnoid hemorrhage that led to brain death less than 24
      hours later. This case demonstrates the severe and prolonged coagulopathy that
      can result from ingestion of brodifacoum, a compound that has a toxic potency
      about 200-fold that of warfarin and a half-life as much as 60 times longer.

PMID- 1346955
TI  - Specificity and mode of action of the muscle-type protein-arginine deiminase.
AB  - The primary and secondary specificities and mode of action of the muscle-type
      protein-arginine deiminase (PAD) were investigated using various derivatives of
      Arg and its homologues, as well as Arg-containing peptides by quantitative
      analyses of the reaction products on reverse-phase HPLC. The enzyme converted
      benzoyl-D-Arg-p-nitroanilide into its citrulline derivative at 18% of the rate of
      the L-isomer, while the D-Arg residues in peptides were not deiminated to a
      significant extent. This suggests that PAD does not have strict stereospecificity
      and it is dependent on the structure of the residues or groups on both sides of
      the target Arg residue. In contrast, the benzoyl-/-ethyl ester derivatives of
      homoarginine, alpha-amino-beta-guanidino-propionic acid, canavanine, and NG
      methyl-Arg, exhibited poor PAD susceptibility, suggesting that the length and
      nature of the arm as exactly three CH2 groups, and the integrity of the guanidyl
      group are quite strict specificity determinants. The enzyme action on Arg
      residues in peptides depends greatly on their position in the sequence, and on
      the nature of the neighboring residues. For example, deimination of Arg residues
      situated at positions 1-3 from the NH2-terminus, except for those preceded by a
      carbobenzoxy- or benzoyl-group, were in most cases very slow, whereas those at
      the COOH-terminus were deiminated relatively faster. A single Arg residue
      sandwiched between two Pro residues was not deiminated at all, while a pair of
      Arg residues between two Pro were deiminated moderately. Consequently, PAD
      exhibited a variety of modes of action on more than one Arg residues in the
      peptides tested. The results suggest the applicability of PAD, albeit quite
      limited, for selective modification of certain Arg residues in peptides and
      proteins by appropriately controlling reaction time and several other parameters.
      The PAD's mode of action was compared with those of three Arg-bond cleaving
      proteases.

PMID- 1346956
TI  - Pharmacokinetics and antibacterial activity of daily gentamicin.
AB  - Twenty full term neonates with suspected bacterial infection were randomly
      assigned to a once daily or a twice daily dosage regimen with gentamicin (4
      mg/kg/day). Concomitantly all patients were treated with ampicillin (200
      mg/kg/day). The gentamicin concentration time curves were analysed by an open two
      compartment model under steady state conditions on day 4 of treatment. The mean
      theoretical maximum serum concentration in the group taking gentamicin once daily
      (10.9 micrograms/ml) was significantly higher than in the group taking it twice
      daily (7.4 micrograms/ml). Potentially toxic serum concentrations were never
      reached. Mean trough concentrations were comparable in both groups (once daily
      0.8 micrograms/ml; twice daily 1.0 micrograms/ml). Urinary alanine aminopeptidase
      excretion increased during and even two days after end of treatment in both
      groups without any significant differences. The results of the dynamic in vitro
      model revealed that both dosage schedules showed comparable bactericidal effects
      on pathogens inhibited by low concentrations of gentamicin like Escherichia coli
      and Staphylococcus aureus. However the once daily regimen was significantly
      superior in isolates with high minimal inhibitory concentrations.

PMID- 1346957
TI  - Demonstration of passenger leukocytes in a case of Epstein-Barr virus
      posttransplant lymphoproliferative disorder using restriction fragment length
      polymorphism analysis.
AB  - Lymphocytic populations of the posttransplant lymphoproliferative disorder in a
      completely matched renal allograft and a recipient's regional lymph node were
      examined, using restriction fragment length polymorphism analysis with probe
      YNH24 to the variable number tandem repeat D2S44. The donor's DNA was found in
      lymphocytes extracted from both the grafted kidney and the recipient's lymph node
      26 days after engraftment. In both these organs, the results of in situ
      hybridization with a terminally biotin-labeled oligonucleotide probe to the Not I
      tandem repeat region of the Epstein-Barr virus (EBV) genome, as well as those of
      Southern blot hybridization to the EBV nuclear antigen region of the EBV genome,
      were positive. These findings confirmed the presence of the donor's lymphocytes
      ("passenger leukocytes") in the host nodal tissue in human renal transplantation
      and implicated EBV as playing a role in the development of posttransplant
      lymphoproliferative disorder. It is speculated that the EBV proliferative
      stimulus contributed to the recipient and the donor lymphocyte expansions.
      Alternatively, the proliferation of both lymphocyte populations could result from
      a mutual stimulation by minor histocompatibility or other antigens.

PMID- 1346959
TI  - Interaction between secretory leucocyte proteinase inhibitor and bronchial mucins
      or glycopeptides. Physiopathological implications for the protection of mucins
      against proteolysis by human leucocyte elastase.
AB  - The interaction of secretory leucocyte proteinase inhibitor with bronchial mucins
      and glycopeptides was studied by means of c.d. spectroscopy. The interaction with
      mucins was characterized by an increase in organized structure of alpha-helical
      type, as evidenced by the appearance in the difference spectra of two positive
      bands at 208 and 218 nm. This phenomenon was correlated with the amount of
      inhibitor present in the mixtures, suggesting that the change was inherent to the
      inhibitor. Surprisingly, when the inhibitor was mixed with acid glycopeptides,
      difference c.d. spectra showed a decrease in organized structure, characterized
      by a negative minimum at 196 nm. Glycopeptides treated with neuraminidase gave
      similar profiles of difference spectra in three different mixtures, indicating
      that the interaction was smaller. The interaction between the inhibitor and
      mucins was also studied for its ability to modify in vitro the proteolytic
      activity of human leucocyte elastase. Mucins alone were degraded by that
      proteinase into glycopeptides of Mr 400,000-500,000, whereas mucins mixed with
      inhibitor before adding elastase were proteolysed to a lesser extent. These data
      demonstrate that the secretory leucocyte proteinase inhibitor interacts with
      mucins and consequently is capable of protecting the mucins against proteolysis
      by elastase.

PMID- 1346960
TI  - Novel genetic markers of rheumatoid arthritis in Chilean patients, by DR
      serotyping and restriction fragment length polymorphism analysis.
AB  - OBJECTIVE: The analysis of genetic markers of rheumatoid arthritis (RA) in a
      population in which the DR4 serotype is not strongly associated with the disease.
      METHODS: Chilean RA patients (56 seropositive and 22 seronegative) and 141
      controls were studied by serotyping. Southern blot analysis of Bam HI restriction
      fragment length polymorphism (RFLP) was done in genomic DNA from 46 patients with
      seropositive RA, 17 patients with seronegative RA, and 45 controls, using a
      complementary DNA probe specific for DRB1 genes. RESULTS: The prevalence of the
      HLA-DR9 haplotype was strikingly higher in seropositive RA patients (21%) than in
      controls (3%) (Pcorr less than 0.0008, by Fisher's exact test; relative risk [RR]
      = 9.34). The prevalence of DR4 and DR1 haplotypes, although slightly increased,
      did not achieve a significant preponderance. The simultaneous presence of two Bam
      HI fragments (3.6 kb and 4.5 kb) was found with higher prevalence in seropositive
      patients (83%; RR = 9; Pcorr less than 0.00002) than in controls (36%), and
      seemed higher in seronegative RA patients as well (71%; RR = 4). Furthermore, its
      prevalence remained increased in comparisons of DR4 positive controls (36%) with
      DR4 positive seropositive patients (100%; RR = 67; Pcorr less than 0.0002) and
      DR4 positive seronegative patients (100%; RR = 36; Pcorr less than 0.006), even
      after excluding the DR9 positive individuals. A tendency toward higher
      association with DR1 seropositive RA patients (67%; RR = 12), a group with no DR4
      or DR9 positive individuals, than in DR1 positive controls (14%), was also
      observed. CONCLUSION: The HLA-DR9 haplotype was definitively consolidated as a
      very strong genetic marker exclusively for seropositive RA in Chilean patients,
      as suggested by our previous observations. RFLP analysis showed that the
      simultaneous presence of 3.6-kb and 4.5-kb Bam HI fragments constituted a better
      RA marker than did any of the heretofore studied haplotypes. These fragments
      together would be linked to RA independently of the DR1, DR4, and DR9 haplotypes.
      The overall evidence indicates that Chilean seropositive RA patients display a
      genetic background that is different from that underlying RA susceptibility in
      other populations and suggests the existence of common, as well as distinct,
      genetic elements predisposing to seronegative and seropositive RA.

PMID- 1346958
TI  - Global ischaemia induces a biphasic response of the mitochondrial respiratory
      chain. Anoxic pre-perfusion protects against ischaemic damage.
AB  - Studies of Langendorff-perfused rat hearts have revealed a biphasic response of
      the mitochondrial respiratory chain to global ischaemia. The initial effect is a
      30-40% increase in the rate of glutamate/malate oxidation after 10 min of
      ischaemia, owing to an increase in the capacity for NADH oxidation. This effect
      is followed by a progressive decrease in these oxidative activities as the
      ischaemia is prolonged, apparently owing to damage to Complex I at a site
      subsequent to the NADH dehydrogenase component. This damage is exacerbated by
      reperfusion, which causes a further decrease in Complex I activity and also
      decreases the activities of the other complexes, most notably of Complex III.
      Perfusion for up to 1 h with anoxic buffer produced only the increase in NADH
      oxidase activity, and neither anoxia alone, nor anoxia and reperfusion, caused
      loss of Complex I activity. Perfusing for 3-10 min with anoxic buffer before 1 h
      of global ischaemia had a significant protective effect against the ischaemia
      induced damage to Complex I.

PMID- 1346961
TI  - The Second International Symposium on Pollinosis in the Mediterranean Area. March
      22-26, 1992, Herzliya, Israel. Abstracts.

PMID- 1346962
TI  - Inactivation of placental factor XIIIa by acrylamide.
AB  - Acrylamide rapidly and irreversibly inactivates thrombin activated Factor XIIIa,
      without affecting neither the intact zymogen nor its proteolytic activation. The
      inactivation is strictly dependent on the presence of calcium ions and is
      accompanied by a decrease in the number of free and total thiol residues,
      suggesting that cysteine residue(s), whose reactivity is modulated by calcium, is
      (are) probably responsible for the acrylamide-directed inactivation.

PMID- 1346964
TI  - Autoradiographic localization of dopamine uptake sites in the rat brain with 3H
      GBR 12935.
AB  - The regional distribution of dopamine (DA) uptake sites in the rat brain has been
      studied by quantitative autoradiography using [3H]GBR 12935 as a ligand. The
      binding of [3H]GBR 12935 to striatal sections was saturable and of high affinity
      (Kd = 1.6 nM); it occurred at a single population of sites and possessed the
      pharmacological features of the DA uptake sites. The highest densities of [3H]GBR
      12935 binding sites were found in the caudate-putamen, nucleus accumbens,
      olfactory tubercle, ventral tegmental area and substantia nigra (especially in
      the pars compacta). Moderate levels of [3H]GBR 12935 binding were observed in
      globus pallidus, thalamus, hypothalamus, hippocampus, amygdala (basolateral
      nucleus) and prefrontal and singular cortices. This regional distribution of
      [3H]GBR 12935 binding closely correlated with the reported distribution of
      dopaminergic nerve terminals. The topographical distribution of [3H]GBR 12935 has
      also been studied in detail in striatal subregions and this distribution was
      compared, using quantitative TH immunoreactivity, to the density of striatal
      dopaminergic nerve terminals. There is good overlapping between these two
      regional distributions, the highest density of both markers was found in the
      lateral part of the striatum and a similar rostro-caudal gradient has been
      observed. A dopaminergic denervation caused a complete loss of [3H]GBR 12935 in
      basal ganglia ipsilateral to the lesion.

PMID- 1346966
TI  - AIDS patients can tolerate a substantial loss of CD4 cells.

PMID- 1346965
TI  - The contribution of the different binding sites of the N-methyl-D-aspartate
      (NMDA) receptor to the expression of behavior.
AB  - The effects of competitive (CGP 37849 and CGP 39551) and non-competitive
      (dizocilpine) N-methyl-D-aspartate (NMDA) antagonists were tested in three animal
      models (catalepsy, sniffing, locomotion) and, in addition, the modulation of
      these effects by an agonist of the strychnine-insensitive glycine binding site
      was investigated. Both competitive and non-competitive NMDA antagonists reduced
      neuroleptic-induced catalepsy. Weak sniffing was induced by the competitive
      antagonist but strong sniffing by the non-competitive NMDA antagonist. Due to
      muscle relaxation the competitive antagonist reduced locomotion, in contrast to
      stimulation of locomotor activity induced by the non-competitive NMDA antagonist.
      The glycine agonist (D-cycloserine) potentiated the effects of the non
      competitive but antagonized those of the competitive NMDA antagonist.

PMID- 1346963
TI  - Risks versus benefits of inhaled beta 2-agonists in the management of asthma.
AB  - The therapeutic goal for the treatment of asthma should be to suppress bronchial
      mucosal inflammation with preventive drugs such as inhaled corticosteroids, and
      to relieve symptoms of wheezing and breathlessness with bronchodilator drugs. The
      lower recommended doses of inhaled beta 2-agonists produce rapid effective
      bronchodilatation without systemic adverse effects; higher doses may produce
      substantial improvements in airway response which may help patients with more
      severe airflow obstruction. Higher doses of inhaled beta 2-agonists also cause
      dose-related systemic adverse beta 2 effects including tremor, tachycardia,
      hypokalaemia and associated electrocardiographic sequelae. In this respect,
      although fenoterol appears to cause greater extrapulmonary beta 2-mediated
      adverse effects at higher doses, there is no evidence to suggest that it is any
      less beta 2-selective. There is also some evidence to suggest that use of regular
      inhaled beta 2-agonists may cause increased bronchial hyperreactivity and
      possibly deterioration in disease control. Patients who require such regular use
      should therefore be given additional anti-inflammatory therapy with inhaled
      corticosteroids. The recent availability of novel, longer-acting inhaled beta 2
      agonists such as salmeterol and formoterol will also make necessary a careful
      reappraisal of their long term use in patients with asthma.

PMID- 1346967
TI  - A case of chronic lymphocytic leukaemia with myeloid associated antigen.

PMID- 1346969
TI  - Scientists versus parasites: who are the winners? Molecular Understanding and
      Control of Parasitic Diseases: a Jacques Monod conference sponsored by the Centre
      National de la Recherche Scientifique, Roscoff, France, July 1-5, 1991.

PMID- 1346968
TI  - An inside look at a small cell. Yeast Cell Biology sponsored by Cold Spring
      Harbor Laboratory, Cold Spring Harbor, NY, USA, August 13-18, 1991.
AB  - It should be apparent from this review that new genes important for cell function
      are rapidly being discovered in yeast. In the not too distant future, the
      sequence of the yeast genome will provide us with a list of all of the proteins
      needed to make a cell. The challenge will then be to continue to develop
      biochemical and genetic approaches to uncover the function of these proteins.
      Clearly, yeast is going to play a major role in the future of cell biology and
      the power of this small eukaryote is just beginning to be tapped.

PMID- 1346970
TI  - Development shows some backbone. HFSP Workshop on Genetic Control of Vertebrate
      Development cosponsored by the Human Frontier Science Program, European Science
      Foundation, and European Molecular Biology Organization, Les Diablerets,
      Switzerland, May 26-30, 1991.
AB  - This meeting aptly illustrated the power of a combined analysis of development in
      a range of vertebrate systems. Each system has its own inherent strengths: the
      mouse has gene transfer technology and targeted mutagenesis, the frog and chick
      have experimental embryology, and the zebrafish has genetics. It is the
      synergistic effect of considering all of these systems in combination that is
      without measure. In the past, the study of vertebrate development has been
      relegated to a largely descriptive phase. Initially, this was through analysis of
      morphological changes taking place during development. More recently, this has
      taken the form of cataloging the expression patterns of genes transcribed in
      development. It is clear that we are now entering an era when a functional
      analysis of development can get underway.

PMID- 1346971
TI  - The stem cell mavens had a blast. Second International Symposium on the Molecular
      Biology of Hematopoiesis, Innsbruck, Austria, July 14-18, 1991.

PMID- 1346972
TI  - Sensational science. Sensory Transduction: 45th Annual Symposium of the Society
      of General Physiologists, Marine Biological Laboratory, Woods Hole, MA, USA,
      September 5-8, 1991.
AB  - In the course of several days of formal and informal talks, in the idyllic
      setting of Woods Hole, the impression grew among many of the participants that
      useful common themes have emerged for comparison among sensory transduction
      systems. Many of these were made explicit in a talk on biophysical principles of
      sensory transduction by Steven Block (Cambridge, MA, USA). In one hour, Block
      summarized the rest of the symposium and much more, in a dazzling tour through
      the senses. One of his points was that all sensory transducers must fulfill
      common goals: detection of the signal, which involves the functions of
      collecting, selecting or tuning, and capture of the stimulus; amplification, to
      raise the signal energy (without adding noise) for transmission to other parts of
      the organism; adaptation or feedback, to extract behaviorally useful parts of the
      signal; termination, to re-prime the system for the next signal; and encoding,
      which puts the information in a useful form for downstream processing or effector
      elements. Another useful comparison was between quantum-detecting systems, such
      as photoreception and olfaction, where the energy of the stimulus quantum (photon
      or odor ligand) is large and a uniform response is desired, and noise-limited
      systems, such as auditory transduction or magnetoreception, where thermal noise
      is larger than the smallest stimuli and time-averaging helps pull the signal out
      of the noise. A third observation from Block was that sensory transduction
      systems--while often performing at physical limits--have not necessarily been
      perfected by the process of evolution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346973
TI  - Downstream of the homeotic genes.
AB  - The homeotic genes of Drosophila melanogaster determine which structures form in
      each of the body segments. Disrupting the function of the homeotic genes causes
      body parts found in one domain of the animal to be replaced by body parts
      normally found elsewhere. Each of the homeotic genes encodes a protein, or a
      closely related family of proteins, which is capable of binding DNA and
      controlling the transcriptional activities of downstream genes. The homeotic
      genes are in the middle of a complex regulatory network, and many of the genes
      that control homeotic expression have been well characterized. However, very
      little is known about what comes after the homeotic genes, the downstream genes
      whose activities are regulated by the homeotic genes. Here, we review the known
      relationships between the homeotic proteins and the few identified target genes.
      The details of these interactions may be characteristic and may thus guide the
      search for additional targets.

PMID- 1346974
TI  - 5-Chlorolevulinate modification of porphobilinogen synthase identifies a
      potential role for the catalytic zinc.
AB  - Porphobilinogen synthase (PBGS) is a Zn(II) metalloenzyme which catalyzes the
      asymmetric condensation of two molecules of 5-aminolevulinate (ALA). The nitrogen
      of the first substrate ends up in the pyrrole ring of product (P-side ALA); by
      contrast, the nitrogen of the second substrate molecule remains an amino group (A
      side ALA). A reactive mimic of the substrate molecules, 5-chlorolevulinate (5
      CLA), has been prepared and used as an active site directed irreversible
      inhibitor of PBGS. Native octameric PBGS binds eight substrate molecules and
      eight Zn(II) ions, with two types of sites for each ligand. As originally
      demonstrated by Seehra and Jordan [(1981) Eur. J. Biochem. 113, 435-446], 5-CLA
      inactivates the enzyme at the site where one of the two substrate molecules
      binds, and modification at four sites per octamer (one per active site) affords
      near-total inactivation. Here we report that 5-CLA-modified PBGS (5-CLA-PBGS) can
      bind up to four substrate molecules and four Zn(II) ions. Contrary to the
      conclusion of Seehra and Jordan, we find that the preferential site of 5-CLA
      inactivation is the A-side ALA binding site. On the basis of the dissociation
      constants, the metal ion binding sites lost upon 5-CLA modification are assigned
      to the four catalytic Zn(II) sites. 5-CLA-PBGS is shown to be modified at
      cysteine-223 on half of the subunits. We conclude that cysteine-223 is near the
      amino group of A-side ALA and propose that this cysteine is a ligand to the
      catalytic Zn(II). The vacant substrate binding site on 5-CLA-PBGS is that of P
      side ALA. We have used 13C and 15N NMR to view [4-13C]ALA and [15N]ALA bound to 5
      CLA-PBGS. The NMR results are nearly identical to those obtained previously for
      the enzyme-bound P-side Schiff base intermediate [Jaffe et al. (1990)
      Biochemistry 29, 8345-8350]. It appears that, in the absence of the catalytic
      Zn(II), 5-CLA-PBGS does not catalyze the condensation of the amino group of the P
      side Schiff base intermediate with the C4 carbonyl derived from 5-CLA. On this
      basis we propose that Zn(II) plays an essential role in formation of the first
      bond between the two substrate molecules.

PMID- 1346976
TI  - Inhibition of normal B-cell function by human immunodeficiency virus envelope
      glycoprotein, gp120.
AB  - Despite the occurrence of hypergammaglobulinemia in human immunodeficiency virus
      (HIV) infection, specific antibody production and in vitro B-cell differentiation
      responses are frequently impaired. In this study, we have examined the effects of
      HIV envelope glycoprotein gp120 on T-helper cell function for B cells. In the
      culture system used, B-cell functional responses were dependent on T-B-cell
      contact, since separation of T and B cells in double chambers by Transwell
      membranes rendered the B cells unresponsive in assays of antigen-induced B-cell
      proliferation and differentiation. Cytokines secreted by T cells were also
      essential, since anti-CD3 monoclonal antibody (mAb)-activated, paraformaldehyde
      fixed T-cell clones failed to induce B-cell proliferation and differentiation.
      Pretreatment of the CD4+ antigen-specific T cells with gp120 was found to impair
      their ability to help autologous B cells, as determined by B-cell proliferation,
      polyclonal IgG secretion, and antigen-specific IgG secretion. The gp120-induced
      inhibition was specific in that it was blocked by soluble CD4. Furthermore, only
      fractionated small B cells (which are T-cell-dependent in their function)
      manifested impaired responses when cultured with gp120-treated T cells. Antigen
      induced interleukin (IL)-2 and IL-4, but not IL-6, secretion were markedly
      reduced in gp120-treated T-cell clones. Addition of exogenous cytokines failed to
      compensate for defective helper function of gp120-treated T cells. The findings
      in this study indicate that gp120 impairs helper functions of CD4+ T cells by
      interfering with T-B-cell contact-dependent interaction; the inhibitory effects
      of soluble envelope proteins of HIV may contribute to the immunopathogenesis of
      the HIV-associated disease manifestations.

PMID- 1346975
TI  - Hemophilia B caused by five different nondeletion mutations in the protease
      domain of factor IX.
AB  - Factor IX is a multidomain protein and is the proenzyme of a serine protease,
      factor IXa, essential for hemostasis. In this report, we describe the molecular
      basis of hemophilia B (deficiency of factor IX activity) in five patients who
      have neither deletions nor rearrangements of the factor IX gene. By enzymatic
      amplification and sequencing of all exons and promoter regions, the following
      causative mutation in the protease domain of factor IX was identified in each
      patient: IXSchmallenberg: nucleotide 31,215G----T, Ser365Ile; IXVarel: nucleotide
      31,214A----G, Ser365Gly; IXMechtal: nucleotide 31,211G----C, Asp364His;
      IXDreihacken: nucleotide 30,864G----A, Arg248Gln; and IXMonschau: nucleotide
      30,855A----T, Glu245Val. In IXVarel, nucleotide 31,213T was also replaced by C,
      which results in a silent mutation (GAT----GAC) at Asp-364. Thus, this patient
      has a double base-pair substitution of TA to CG at nucleotides 31,213 and 31,214
      but only a single amino acid change of Ser-365 to Gly. This patient also
      developed an antibody to factor IX during replacement therapy, which suggests
      that deletion of the factor IX gene is not necessary for development of the
      antibody in hemophilia B patients. The levels of plasma factor IX antigen in the
      patients ranged from 40% to 100% except for IXDreihacken (Arg248Gln), in which
      case it was approximately 4% of normal. The Ser365Gly and Ser365Ile mutants are
      nonfunctional because of lack of the active site serine residue. Mutant Asp364His
      is inactive because it cannot form the hydrogen bond between the carboxylate
      group of Asp-364 and the alpha-amino group of Val-181 generated after activation.
      As observed in other homologous serine proteases, this hydrogen bond is essential
      for maintaining the correct active site conformation in normal factor IXa (IXaN).
      Purified Arg248Gln had approximately 41% and Glu245Val had approximately 17% of
      the activity of normal factor IX (IXN) in a partial thromboplastin time (aPTT)
      assay. In immunodot blot experiments, the isolated Glu245Val mutant did and the
      Arg248Gln mutant did not bind to an anti-IXN monoclonal antibody that has been
      shown previously to inhibit the interaction of factor VIIIa with factor IXaN. We
      have recently shown that a high-affinity calcium binding site exists in the
      protease domain of IXN; among the proposed Ca(2+)-binding ligands is the carboxyl
      group of Glu-245. Further, a part of the epitope for the above antibody was shown
      to be contained in the 231 to 265 residue segment of factor IX.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1346977
TI  - Pain management: trends in the 1990s.

PMID- 1346978
TI  - Testicular function in patients with hypospadias associated with enlarged
      prostatic utricle.
AB  - Of 485 patients with hypospadias who underwent urethrography, enlarged prostatic
      utricles were found in 173 (35.7%). Utricles with a higher grade of enlargement
      were seen mainly in patients with a severe degree of hypospadias. Serum
      testosterone levels before and after 3 days' treatment with human chorionic
      gonadotrophin were determined by radioimmunoassay in 97 prepubertal boys with
      hypospadias and enlarged prostatic utricles. Lower levels of serum testosterone
      were found after hormonal stimulation in 22 patients with high grade utricular
      enlargement when compared with 5 controls and 75 patients with low grade
      enlargement; the difference was statistically significant. This finding supports
      the hypothesis that utricular enlargement may be due to androgenic insufficiency
      during the critical period of organogenesis.

PMID- 1346979
TI  - Effect of alpha-adrenergic blockade with prazosin on large coronary diameter
      during exercise.
AB  - BACKGROUND: Exercise-induced dilation of coronary resistance vessels is limited
      by alpha-adrenergic mechanisms. However, the effect of alpha-adrenergic
      mechanisms on large coronary arteries during exercise is not known. METHODS AND
      RESULTS: In the present study, sonomicrometry was used to measure circumflex
      coronary arterial diameter during treadmill exercise before and after alpha 1
      adrenergic blockade with prazosin in eight instrumented dogs. Before infusion of
      prazosin, exercise caused a fall in coronary vascular resistance (2.1 +/- 0.4 to
      1.6 +/- 0.2 units, p less than 0.05) and dilation of the circumflex coronary
      artery (4.66 +/- 0.37 to 4.79 +/- 0.34 mm, p less than 0.05). Intracoronary
      infusion of prazosin during exercise caused a further decrease in coronary
      vascular resistance (1.6 +/- 0.2 to 1.4 +/- 0.2 units, p less than 0.05) and a
      further increase in circumflex coronary arterial diameter (4.79 +/- 0.34 to 4.83
      +/- 0.34 mm, p less than 0.05). Intracoronary infusion of vehicle without
      prazosin during exercise did not cause a further decrease in coronary vascular
      resistance or increase in coronary diameter. Prazosin caused no significant
      increase in heart rate, aortic pressure, or coronary blood flow. Therefore, both
      small coronary resistance vessels and large epicardial coronary arteries dilated
      during exercise and dilated further after alpha-adrenergic blockade. CONCLUSIONS:
      This finding indicates that alpha 1-adrenergic activity during exercise limits
      dilation of both large and small coronary arteries.

PMID- 1346981
TI  - Proceedings of the Congress of Neurological Surgeons, Los Angeles, California,
      1990.

PMID- 1346980
TI  - Cholesterol lowering as a treatment for established coronary heart disease.

PMID- 1346982
TI  - Catalytic and immunologic similarities between monkey and human liver cytochrome
      P-450db1 (human cytochrome P-450 2D6).
AB  - In vivo pharmacogenetic studies have suggested that the monkey may be an animal
      model for the human polymorphism of cytochrome P-450 2D6 (also called cytochrome
      P-450db1). In the present study, the catalytic, immunologic, and electrophoretic
      properties of cytochrome P-450db1 in liver microsomes from African green monkeys
      (Cercopithecus aethiops) were examined and compared with P-450db1 in human liver
      microsomes. Using sparteine as the substrate, the activity of microsomal P-450db1
      from the two sources was indistinguishable in terms of the pattern of sparteine
      metabolites produced, the apparent Ki values of 8 competitive inhibitors (r =
      0.94, p less than 0.001), and the extent of immunoinhibition by anti-rat P-450db1
      antibody. Kinetic analyses demonstrated that the apparent KM values of the high
      affinity component of sparteine oxidation in monkey liver microsomes fell within
      the range observed in human livers; the Vmax of this component was as much as six
      times greater than the highest value reported for human liver. Western
      immunoblots showed a protein band in monkey liver microsomes that co-migrated
      with P-450db1 in human liver. The high degree of similarity observed here between
      P-450db1 of monkey and human liver microsomes suggests that the monkey will be a
      good animal model for P-450db1 enzyme studies, and possibly for studies of the
      role of this enzyme in drug abuse and dependence.

PMID- 1346983
TI  - Disposition of the novel serotonin agonist, LY228729, in monkeys and rats.
AB  - The disposition of a novel 5HT-1a agonist, LY228729, was studied in rats after
      oral administration and in monkeys after both i.v. and oral administration of a
      radiolabeled drug. Plasma concentrations of LY228729 declined with a half-life of
      2.3 and 1.5 hr in monkeys after oral dosing and i.v. administration,
      respectively, and 1.9 hr in rats dosed orally. Peak plasma concentrations of the
      N-despropyl metabolite were greater than the parent drug following oral
      administration in both rats and monkeys and declined with a half-life of 3.2-3.5
      hr. Plasma levels of total radioactivity rapidly exceeded that of the parent drug
      in both species. Radioactivity was eliminated more slowly, with terminal half
      lives of 39.4 hr in the monkey and 48.6 hr in the rat. The parent drug and its
      despropyl metabolite accounted for only a small percentage of the total
      radioactivity in the plasma. Following i.v. and oral administration,
      radioactivity was eliminated predominantly in the urine of monkeys, but was
      distributed evenly between the urine and feces of rats. Parent drug and the N
      despropyl metabolite were the major products in rat urine. In the monkey, the
      major metabolite was an uncharacterized polar compound.

PMID- 1346984
TI  - Substituted pyridines: nonsteroidal inhibitors of human placental aromatase
      cytochrome P-450.
AB  - The binding to human placental aromatase cytochrome P-450 and resulting extent of
      inhibition was examined for pyridine, pyridines substituted at the 2-, 3-, or 4
      positions with phenyl or benzoyl groups, and the nonpyridinic structural analogs
      biphenyl and benzophenone. Spectral binding studies with partially purified
      aromatase indicated that pyridine, 3- and 4-phenylpyridines, and 3- and 4
      benzoylpyridines interact at the active site via ligation of the pyridinic
      nitrogen to heme iron, as judged by the type II difference spectra. The apparent
      dissociation constants for these compounds are 2.1, 0.11, 0.09, 2.6, and 0.27 mM,
      respectively. Biphenyl, benzophenone, and 2-benzoylpyridine show exclusively a
      hydrophobic interaction in the presence of the substrate, androst-4-ene-3,17
      dione, to give reverse type I difference spectra, with apparent spectral
      dissociation constants of 0.14, 0.42, and 1.8 mM, respectively. 2-Phenylpyridine
      shows a unique spectrum, previously not observed with cytochrome P-450, that has
      components of both type I and type II spectra. As measured by tritium ion release
      from [1 beta-3H]androst-4-ene-3,17-dione, competitive inhibition of human
      microsomal aromatase activity was observed with pyridine, 2-, 3-, and 4
      phenylpyridines, biphenyl, and benzophenone, with Ki values of 320, 62, 1.48,
      0.36, 750, and 130 microM, respectively. In contrast, 2-, 3-, and 4
      benzoylpyridines exhibited complex kinetic behavior from which inhibition
      constants could not be obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346986
TI  - Comparative metabolism and covalent binding of procainamide by human leukocytes.
AB  - Activated neutrophils and monocytes were found to metabolize procainamide to a
      reactive hydroxylamine. In contrast, there was little or no metabolism by
      lymphocytes or platelets. Therefore, it appears that only leukocytes that contain
      myeloperoxidase can metabolize procainamide to a significant degree. There was no
      difference in the degree to which neutrophils from males or females metabolized
      procainamide; however, monocytes from males formed significantly more
      hydroxylamine than did monocytes from females. By use of radiolabeled
      procainamide, covalent binding of procainamide to leukocytes was detected, and
      the degree of binding correlated with the cells' ability to oxidize procainamide.
      These findings suggest that myeloperoxidase is the major enzyme involved in the
      formation of reactive metabolites by leukocytes, a pathway that we propose may be
      responsible for procainamide-induced lupus and agranulocytosis.

PMID- 1346985
TI  - Pharmacokinetics and tissue distribution of 2-fluoro-beta-alanine in rats.
      Potential relevance to toxicity pattern of 5-fluorouracil.
AB  - Clinical pharmacokinetic studies in our laboratory demonstrated that 2-fluoro
      beta-alanine (FBAL), the major catabolite of fluorouracil (FUra), has a prolonged
      elimination with an approximately 150-fold longer half-life than that of the
      unchanged drug in humans [Heggie et al.: Cancer Res. 47, 2203-2206 (1987)].
      Recent studies have suggested that FUra catabolites, such as FBAL, may have a
      role in neurotoxicity and cardiotoxicity that may occur during FUra chemotherapy
      [Okada et al.: Acta Neuropathol. 81, 66-73 (1990)]. This study was undertaken to
      determine the kinetics and tissue distribution of FBAL in rats following iv bolus
      administration of radiolabeled FBAL. Plasma disappearance curves for FBAL could
      be described by the sum of three exponentials, with half-lives of 0.26, 12.1, and
      8426 min. Radioactivity, consisting mainly of FBAL-bile acid conjugates, was
      excreted in bile within 30 sec of iv bolus administration of FBAL and continued
      throughout the experimental period at concentrations 10-100-fold higher than that
      of the corresponding plasma level. Urinary excretion, consisting mainly of free
      FBAL, represented the major pathway of elimination of FBAL, with 40% of the
      administered dose excreted within 24 hr and approximately 70% over 192 hr. Fecal
      excretion was a minor pathway of elimination of FBAL, with approximately 10% of
      the administered dose excreted over 192 hr. During the initial 30 min, the
      highest levels of tissue radioactivity were found in the kidneys, liver, spleen,
      lungs, and heart. Radioactivity was retained over longer time periods in the
      enterohepatic circulation, central nervous system, heart, and skeletal
      muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346987
TI  - Isolation and identification of the major urinary metabolite of N
      methylpyrrolidinone in the rat.

PMID- 1346988
TI  - Metabolism of enflurane in dogs.

PMID- 1346989
TI  - Formation of a carbamoyl glucuronide conjugate of carvedilol in vitro using dog
      and rat liver microsomes.

PMID- 1346990
TI  - Substrate specificity and other characteristics of a novel aldehyde dehydrogenase
      present in female DBA/2 mouse liver.

PMID- 1346991
TI  - Comparisons of hepatic and renal cytochromes P-450-dependent monooxygenases from
      fuzzy and Sprague-Dawley rats.
AB  - The differences in monooxygenase activities between the fuzzy rat, a variant of
      the hairless rat, and the Sprague-Dawley rat were examined. Benzo(a)pyrene
      hydroxylase and benzphetamine N-demethylase activities and cytochrome P-450
      contents were significantly lower in the livers of fuzzy rats than in the livers
      of the Sprague-Dawley rats. The hydroxylase activity in the kidneys of the two
      strains were not significantly different from each other. In comparison to the
      Sprague-Dawley rats, the induction of these enzymic activities by phenobarbital
      and 3-methylcholanthrene were of a lesser magnitude in the fuzzy rats, indicating
      that regulation of the hepatic monooxygenases differed in the two strains.
      Immunoblot data showed that cross-reactivity between antirat P-450IIB1 and
      microsomal protein from phenobarbital-treated rats appeared to be lower in the
      fuzzy rat when compared with the Sprague-Dawley rat. These differences in the
      constitutive enzymes and the differences in the induction of hepatic
      monooxygenases between the two strains of rats may be important determinants in
      studies involving metabolism of drugs and other chemicals following cutaneous
      exposure.

PMID- 1346993
TI  - Characterization of human liver cytochromes P-450 involved in theophylline
      metabolism.
AB  - Theophylline is metabolized in the liver by one or more cytochrome P-450 enzymes.
      To assess the amounts and types of these human cytochromes P-450, we incubated
      theophylline with microsomes prepared from 22 different human livers in the
      presence of NADPH, and measured simultaneous rates of 1- and 3-N-demethylations
      to 3-methylxanthine (3-MX) and 1-methylxanthine (1-MX), respectively; and 8
      hydroxylation to 1,3-dimethyluric acid (1,3-DMU). Under optimal conditions, 3-MX,
      1-MX, and 1,3-DMU formation proceeded with mean Km values of 2.05, 1.93, and 5.34
      mM and Vmax values of 2.28, 2.48, and 23.4 pmol/mg/min, respectively. Formation
      of 3-MX and 1-MX correlated best with amounts of the immunoreactive protein HLd
      (P-450IA2) (p less than 0.05), whereas formation of 1,3-DMU correlated with the
      microsomal content of HLp (P-450IIIA3) and HLj (P-450IIE1). In immunoinhibition
      experiments, incubations conducted with a polyclonal anti-rat P-450c/d antibody,
      the formation of all the three theophylline metabolites (p less than 0.05) was
      significantly inhibited. However, addition of isoform-specific anti-rat-P-450d
      antibodies to the microsomal mixture significantly inhibited 1-N-demethylation,
      selectively, with little (if any) inhibition of 3-N-demethylation or 8
      hydroxylation. Nonspecific cytochrome P-450 inhibition was ruled out by showing
      that erythromycin N-demethylation, an activity catalyzed by HLp, was unaffected
      by either anti-P-450c/d (P-450IA1/IA2) or anti-P-450d. Anti-rat-P-450p antibodies
      failed to block formation of theophylline metabolism, but did inhibit
      erythromycin N-demethylase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346992
TI  - Pharmacokinetic evaluation of two human epidermal growth factors (hEGF51 and
      hEGF53) in rats.
AB  - The pharmacokinetic profiles of two iodinated human epidermal growth factors
      (125I-hEGF51 and 125I-hEGF53) in rats receiving a single intravenous dose have
      been investigated using three independent bioanalytical techniques. Based on a
      tetrachloroacetic acid precipitation methodology, hEGF51 and hEGF53 were found to
      have distribution half-lives of 0.80 +/- 0.2 and 0.80 +/- 0.18 min, and
      elimination half-lives of 79.8 +/- 24.1 and 77.9 +/- 21.1 min, respectively.
      Evaluated by immunoprecipitation, distribution half-lives were 0.59 +/- 0.09 and
      0.63 +/- 0.15 min, and elimination half-lives were 117.8 +/- 22.9 and 118.7 +/-
      38.8 min, respectively. Both precipitation techniques produced similar, parallel
      plasma concentration-time curves, and there were no significant differences in
      other calculated kinetic parameters, including clearance and volume of
      distribution evaluated by either technique. Plasma disposition profiles of both
      peptides were also confirmed by visualization with SDS-PAGE and autoradiography,
      and were found to be similar to those generated by tetrachloroacetic acid and
      immunoprecipitation methods. Thus, three independent methods strongly suggest
      that both peptides have the same disposition profile, which exhibits a very rapid
      disappearance rate in the distribution phase followed by a much slower
      elimination process. These results also indicate that the pharmacokinetic
      behavior of human epidermal growth factor is not altered by deletion of two amino
      acids from the carboxyl terminus. In addition, the incubation study suggests that
      about 23% of the exogenous peptides were associated with red blood cells.

PMID- 1346994
TI  - Microbial models of mammalian metabolism. Biotransformations of N-methylcarbazole
      using the fungus Cunninghamella echinulata.
AB  - The fungal metabolism of N-methylcarbazole (NMC) was investigated during the
      development of microbial models of mammalian metabolism. NMC was metabolized by
      the fungus Cunninghamella echinulata (ATCC 9244) to generate four metabolites:
      carbazole, N-hydroxymethylcarbazole (NHMC), 3-hydroxycarbazole, and 3-hydroxy
      NHMC. Carbazole and NHMC are two major metabolites previously identified in
      mammalian systems, while 3-hydroxycarbazole and 3-hydroxy-NHMC have not been
      previously reported as metabolites of NMC. Structural identification of the four
      metabolites was based upon spectral (UV, MS, and NMR) and chromatographic (TLC
      and HPLC) comparisons with synthetic standards. These studies demonstrate that C.
      echinulata catalyzes the two principal biotransformations observed in mammalian
      systems with NMC: aliphatic hydroxylation to yield the (relatively) stable
      carbinolamine NHMC (with slow decomposition to the N-dealkylated product,
      carbazole) and aromatic hydroxylation in the 3-position.

PMID- 1346995
TI  - Pharmacokinetic evaluation of (-)-6-aminocarbovir as a prodrug for (-)-carbovir
      in rats.
AB  - The recently synthesized carbocyclic 2',3'-didehydro-2',3'-dideoxy-6-deoxy-6
      amino-guanosine [(-)6AC] was evaluated as a prodrug for carbovir, carbocyclic
      2',3'-didehydro-2',3'-dideoxyguanosine [(-)CBV] in seven male Sprague-Dawley
      rats. A randomized three-way cross-over design was used. Rats were assigned to
      receive the following treatments: a 20 mg/kg (-)6AC infusion, 40 mg/kg (-)6AC
      orally, and a 20 mg/kg (-)CBV infusion. Blood samples were collected over 480
      min, and urine was collected for up to 48 hr. A 2- to 3-day washout period was
      observed between treatments. Following i.v. infusion, (-)6AC concentrations in
      the blood declined rapidly in a monoexponential pattern with an elimination half
      life of 11.3 +/- 3.3 min (mean +/- SD, n = 7). The time-averaged total body
      clearance was 115.7 +/- 32.6 ml/min/kg. The fraction of the dose excreted
      unchanged in urine was 0.28 +/- 0.06. The fraction of the (-)6AC dose metabolized
      to (-)CBV was 0.48 +/- 0.14. Following oral administration of (-)6AC, the
      bioavailability of (-)CBV was 46.2 +/- 9.9% (n = 6) in comparison with the
      bioavailability of approximately 20% previously obtained after an oral dose of (
      )CBV. The Cmax of (-)CBV after a 40 mg/kg oral dose of (-)6AC was 1.65 +/- 0.7
      micrograms/ml as compared with the previously reported Cmax of 1.00 microgram/ml
      obtained after a 60 mg/kg oral dose of (-)CBV. (-)6AC has considerable potential
      for the improvement of the extent of absorption of (-)CBV from oral dosing.

PMID- 1346996
TI  - Deacetylation of cinobufagin by rat liver.
AB  - The enzyme system mediating the deacetylation of cinobufagin (CB) at the 16
      position to give deacetylCB was characterized in the rat. Tissue distribution
      studies showed that the highest activity of CB deacetylation was mainly localized
      in the liver microsomal fraction. Some activity was also detected in the serum
      and intestine. Kinetic studies of the enzymatic reaction carried out by
      microsomes demonstrated that the formation of deacetyl-CB increased linearly with
      time up to 60 min and with protein content up to 10 mg. Apparent Km and Vmax
      values calculated from Lineweaver-Burk plots were 2.7 x 10(-4) M and 4.17 nmol/mg
      of protein/min, respectively. Low concentrations of several metal salts (AgNO3,
      MgCl2, CoSO4, and CuCl2) did not affect CB deacetylase activity. Microsomal CB
      deacetylation was inhibited by the organophosphorus compounds cyanox and
      fenitrothion at 1.0 x 10(-6) M. Eserine sulfate, disulfiram, rifampicin, and
      phenacetin at 1.0 x 10(-4) M also decreased CB deacetylase activity. Aspirin,
      sodium fluoride, and EDTA at 1.0 x 10(-3) M did not inhibit the deacetylation. In
      vivo treatment of rats with phenobarbital resulted in a 2-fold increase in
      microsomal CB deacetylase activity. All of these results suggest that the enzyme
      responsible for CB deacetylation is somewhat different from the other
      characterized esterases.

PMID- 1346997
TI  - Characterization of the cytochrome P-450 gene family responsible for the N
      dealkylation of the ergot alkaloid CQA 206-291 in humans.
AB  - The ergot alkaloid CQA 206-291 (CQA) was converted by human liver microsomes (n =
      16) almost exclusively to the N-deethylated metabolite (I), as identified by the
      on-line coupling of liquid chromatography and mass spectroscopy. Metabolite I
      formation exhibited monophasic and linear enzyme kinetics (2.9-300 microM), and a
      5.6-fold interindividual variability (7.2-40.2 nmol/mg/hr). Chemical inhibition
      experiments revealed that imidazole antimycotic agents (ketoconazole, miconazole,
      and clotrimazole) were potent inhibitors of this N-deethylation. Polymorphically
      metabolized substrates (sparteine and phenytoin), well-established cytochrome P
      450 probe substrates (antipyrine and tolbutamide), and steroid hormones
      (estradiol and testosterone) were noninhibitory, indicating that their metabolism
      is catalyzed by forms of cytochrome P-450 that do not catalyze this route of CQA
      biotransformation. The ergot alkaloids--dihydroergotamine, bromocriptine, and SDZ
      208-911--were competitive inhibitors of metabolite I formation, suggesting that
      these compounds are metabolized by similar enzymes. Cyclosporine A was a potent
      competitive inhibitor of CQA metabolism, providing initial evidence that
      formation of metabolite I was catalyzed by proteins of the CYP3 gene family. This
      was substantiated by the finding that CQA metabolism was completely inhibited by
      a polyclonal antibody directed against a pregnenolone 16 alpha-carbonitrile
      inducible cytochrome P-450 of rat liver. The rate of CQA metabolism correlated
      significantly to the level of CYP3A4 expression, the rate of cyclosporine A
      metabolism to each of the primary metabolites (M-1, M-17, and M-21), and the rate
      of midazolam 4-hydroxylation. COS 1 cells transfected with human CYP3A4 and
      CYP3A5 provided direct evidence that these enzymes catalyze the metabolism of
      CQA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1346998
TI  - Pharmacokinetics of 2-ethyl-1,3-hexanediol. II. Nonsystemic disposition following
      single percutaneous or peroral doses in Fischer 344 rats.
AB  - The pharmacokinetics of [1,3-14C]-2-ethyl-1,3-hexanediol (EHD) were investigated
      following single percutaneous doses of 150 mg/kg, applied to male and female
      Fischer 344 rats, or single peroral doses of 1.5 or 150 mg EHD/kg given by gavage
      to male Fischer 344 rats. EHD-derived radioactivity was slowly absorbed through
      skin and relatively rapidly excreted through the urine in a first-order manner
      over 48 hr postdosing. Skin penetration of 14C was sufficiently slow that the
      terminal rate constant for the plasma concentration data had to be derived from
      the absorption phase of this curve, based on the terminal rate constant for a
      comparable intravenous dose plasma curve [Frantz et al.: Drug Metab. Dispos. 19,
      881 (1991)]. Plasma data from perorally doses rats exhibited dose-linearity over
      a 1.5-150 mg/kg range, with plasma 14C concentration vs. time plots for oral
      doses of EHD resembling the iv time-course data. This resulted from a very rapid
      absorption phase (5.5 min t1/2), with plasma 14C levels for both dose levels
      decreasing in a biexponential manner. The major route of excretion after peroral
      doses was in urine, making this mode of excretion consistent for both routes of
      administration evaluated in this study and including the doses given in previous
      iv work. Kinetic analysis confirmed that this route of excretion was first-order.
      HPLC analysis of urine from both routes demonstrated that EHD was metabolized and
      excreted as at least two major, water-soluble urinary metabolites; these
      metabolites were not identified in this investigation. No unmetabolized EHD was
      detected in urine, indicating that EHD may be completely metabolized in the rat.
      Overall, EHD was absorbed, distributed, metabolized, and eliminated from the
      Fischer rat in a first-order manner following either cutaneous or peroral doses.
      The results of this study indicate that the kinetic patterns observed
      experimentally will be dose-proportional for doses administered in the range of
      1.5-150 mg/kg.

PMID- 1346999
TI  - The urinary metabolic profile of metyrapone in the rat. Identification of two
      novel isomeric metyrapol N-oxide metabolites.
AB  - This study was designed to fully characterize the urinary metabolic profile of
      metyrapone following a 50 mg/kg ip dose to male Sprague-Dawley rats. Preliminary
      examination of alkaline dichloromethane extracts of urine by TLC and HPLC showed
      the absence of the intact drug, but the presence of moderate amounts of the two
      isomeric metyrapone mono-N-oxides, together with small amounts of metyrapol and
      the alpha-pyridone metabolite. These compounds have previously been reported as
      in vitro metabolites. Large amounts of two new metabolites of metyrapone were
      also observed and were conclusively identified as the isomeric metyrapol N-oxides
      by a combination of low- and high-resolution mass spectrometry. Quantitation by
      HPLC showed that metyrapol and the two metyrapone mono-N-oxides accounted for 4
      and 10% of the dose, respectively. The two metyrapol mono-N-oxides accounted for
      more than 75% of the dose. These are novel metabolites not previously reported
      either as in vivo or in vitro metabolites.

PMID- 1347000
TI  - Disposition of 1-naphthol in the channel catfish (Ictalurus punctatus).
AB  - The pharmacokinetics, tissue distribution, and metabolism of 1-naphthol were
      examined in the channel catfish (Ictalurus punctatus). Catfish were administered
      [1-14C]1-naphthol intravascularly at 1, 5, or 25 mg/kg or orally at 1 mg/kg.
      Plasma data for 1-naphthol were fitted by a three-compartment pharmacokinetic
      model. There were dose-related changes in the area under the plasma concentration
      vs. time curve, apparent volume of distribution, and total body clearance after
      intravascular dosing. After oral dosing, peak plasma concentrations of 1-naphthol
      occurred at 1 hr; parent compound made up less than 15% of the total
      radioactivity, and the bioavailability was 32%. Plasma protein binding was 92%
      and was independent of concentration. 1-Naphthol and metabolites were rapidly
      eliminated from the tissues after oral dosing; less than 1% of the administered
      dose remained at 24 hr. Renal excretion was the primary route of elimination of
      total 14C. Approximately 60% of the oral dose was excreted in the urine within 48
      hr. Parent 1-naphthol made up 1% of the urinary 14C. Major metabolites in the
      urine were sulfate and glucuronide conjugates, which composed 65 and 28% of the
      total 14C, respectively. Biliary excretion accounted for 7% of the oral dose. The
      glucuronide conjugate and an unidentified polar metabolite made up the majority
      of the biliary 14C. The high capacity of channel catfish for conjugative
      metabolism of 1-naphthol was demonstrated. The dose dependency of pharmacokinetic
      values could not be explained by saturable metabolism or plasma protein binding.

PMID- 1347001
TI  - Cytochrome P-450 isozymes involved in the oxidative metabolism of delta 9
      tetrahydrocannabinol by liver microsomes of adult female rats.
AB  - Oxidative metabolism of delta 9-tetrahydrocannabinol (THC) by liver microsomes
      was studied in female rats. Delta 9-THC was mainly biotransformed to 11-hydroxy
      delta 9-THC (11-OH-delta 9-THC) and 9 alpha,10 alpha-epoxy-hexahydrocannabinol
      (EHHC) by liver microsomal fraction of adult female rat. Two isozymes of
      cytochrome P-450 (P-450) [F-1 (IIC6) and F-2 (IIC12)] were purified from liver
      microsomes of female rats and oxidation activities toward delta 9-THC were
      assessed in the reconstituted system containing NADH-P-450 reductase and
      cytochrome b5. P-450 F-1 showed considerable activity toward 11-OH-delta 9-THC
      formation (10.62 nmol/min/nmol of P-450), whereas P-450 F-2 did not show any
      activity toward delta 9-THC oxidation under the conditions used. Preincubation of
      microsomes with antiserum against P-450 F-1 obtained from rabbits caused a marked
      decrease in 11-OH-delta 9-THC formation, whereas antiserum against P-450 F-2 did
      not exhibit any inhibitory effect on the oxidation of delta 9-THC by liver
      microsomes of adult female rats. Further, antiserum against P-450 F-1 or F-2 did
      not affect the microsomal formation of 9 alpha,10 alpha-EHHC from delta 9-THC.
      These results indicate that P-450 F-1 and its immunochemically related P-450
      isozyme(s) play important roles in the formation of an active metabolite, 11-OH
      delta 9-THC, from delta 9-THC by liver microsomes of adult female rats.

PMID- 1347002
TI  - Felbamate metabolism in pediatric and adult beagle dogs.
AB  - In a metabolism study, three male and three female pediatric dogs and three male
      and three female adult beagle dogs received a single oral dose of 60 mg/kg
      [14C]felbamate. Urine and feces were collected up to 72 hr. Excreta samples were
      extracted with ethyl acetate and 14C metabolite profiles were generated by HPLC
      analysis of the extracts. The total 14C dose recoveries were 88.2% for the
      pediatric and 85.9% for the adult groups; recovery in urine accounted for 61.7
      and 69.7%, respectively. The 14C metabolite profiles in urine and feces were
      similar, with three major peaks corresponding to unchanged felbamate and two
      hydroxylated metabolites. There was no significant sex difference in profiles
      within each age group. However, the sum amount of all metabolites in the urine
      was higher, and the amount of unchanged drug was lower in pediatric dogs. For the
      0-24 hr samples, the metabolites/drug ratio in urine was 2.0-2.1 for pediatric
      dogs and 1.0-1.2 for adult dogs. This indicated a higher metabolic rate in the
      pediatric dogs.

PMID- 1347003
TI  - Metabolism of the anticoagulant peptide, MDL 28,050, in rats.
AB  - Rats were each administered a 9 mg/kg iv bolus dose of a 3H-labeled decapeptide
      anticoagulant, MDL 28,050. Tritium was eliminated rapidly with approximately 50%
      of the dose recovered in urine within the first 6 hr. Renal excretion accounted
      for 68% of the dose, whereas fecal excretion accounted for 16% of the dose.
      Continuous flow fast atom bombardment mass spectrometry was used to identify the
      major urinary metabolites of MDL 28,050. Trace amounts of parent drug were found,
      and other biotransformation products indicated that hydrolysis had occurred at
      four peptide bonds. Two initial sites of hydrolysis were identified as 4I-5P and
      6E-7E, which resulted in the peptide fragments Suc-Y-E-P-I-OH + P-E-E-A-Cha-E-OH
      and Suc-Y-E-P-I-P-E-OH + E-A-Cha-E-OH, respectively. Further metabolism of these
      fragments resulted in the N-terminal pentapeptide and the C-terminal dipeptide.

PMID- 1347005
TI  - [An isolated elevation of gamma-GT].

PMID- 1347004
TI  - Identification of cytochrome P-450IIB1 as a cocaine-bioactivating isoform in rat
      hepatic microsomes and in cultured rat hepatocytes.
AB  - Induction of cytochrome P-450-dependent monooxygenases with phenobarbital (PB) or
      other hepatic drug-metabolizing enzyme inducers in the rat is associated with
      enhanced cocaine hepatotoxicity both in vivo and in cultured rat hepatocytes. To
      demonstrate whether the major PB-inducible P-450 subfamily (P-450IIB) could be
      involved in the metabolic activation of cocaine, rates of cocaine N-demethylation
      (the first step of cocaine bioactivation) and the rate of irreversible (covalent)
      binding of tritiated cocaine to hepatic microsomal proteins (a measure for the
      overall bioactivation) were determined in microsomes from saline or PB-pretreated
      rats. PB pretreatment augmented Vmax (6-fold), but not KM, of cocaine N
      demethylation. Similarly, the rate of irreversible protein binding was 3-fold
      increased in microsomes from PB-pretreated rats as compared with those from
      saline controls. Addition of benzphetamine, a substrate of P-450IIB, markedly
      inhibited cocaine irreversible binding. In addition, various concentrations of
      cocaine inhibited microsomal pentoxyresorufin O-depentylase activity in a
      competitive-type pattern. A polyclonal antibody raised against purified rat P
      450IIB1 markedly inhibited cocaine N-demethylation as compared with control
      incubations with preimmune IgG. Finally, pretreatment of rats with PB potentiated
      cocaine-induced cytotoxicity in primary, short-term cultured hepatocytes,
      assessed as lactate dehydrogenase release into the culture medium. This enhancing
      effect of PB became even more evident in glutathione-depleted cells. These
      results suggest that cocaine is metabolized and bioactivated by P-450IIB1 in the
      rat liver, and that induction of this isoform with various agents may be
      associated with enhanced lethal hepatocyte injury in the rat.

PMID- 1347006
TI  - Dopamine stimulates growth hormone release from the pituitary of goldfish,
      Carassius auratus, through the dopamine D1 receptors.
AB  - Previously, we have demonstrated that ip injection of apomorphine, a nonselective
      dopamine (DA) agonist, increases serum GH levels in the goldfish, suggesting a
      possible role of DA in GH regulation. In the present study, the effects of DA on
      GH release in the goldfish were further characterized using an in vitro
      perifusion system for pituitary fragments. DA increased GH release in a dose
      dependent manner with an ED50 of 0.26 +/- 0.06 microM. SKF38393, a DA D1 agonist,
      mimicked the GH-releasing effect of DA with an ED50 of 0.41 +/- 0.12 microM.
      Stereoselectivity consistent with mammalian DA D1 systems was demonstrated for
      the GH response to SKF38393; only the (+)- but not (-)-enantiomer of SKF38393
      induced a dose-dependent GH release. Two other D1 agonists, SKF77434 and
      SKF82958, were also found to have GH-releasing activity. In contrast, high doses
      (up to 1 microM) of the DA D2 agonists, bromocriptine and LY171555, did not
      affect basal GH levels. The receptor specificity for DA-stimulated GH release was
      further investigated by using D1 and D2 antagonists; the D1 antagonists SCH23390
      and SKF83566 completely abolished the GH response to DA or the D1 agonist
      SKF38393, whereas the D2-specific antagonists domperidone and (-)-sulpiride were
      not effective in this respect. Taken together, the present study demonstrates
      that DA is stimulatory to GH release from the pituitary of goldfish, and its
      action is mediated through receptors resembling the mammalian DA D1 receptors.
      The apparent similarities of the DA D1 receptor pharmacology between the goldfish
      and the mammals also indicate that D1 receptor is highly conserved during
      vertebrate evolution.

PMID- 1347007
TI  - Effects of ovarian steroids on the gonadotropin response to N-methyl-D-aspartate
      and on hypothalamic excitatory amino acid levels during sexual maturation in
      female rats.
AB  - In order to evaluate the involvement of estrogen-progesterone (EP) in the effects
      of N-methyl-D-aspartate (NMDA) receptor stimulation on gonadotropin secretion
      during sexual development in female rats, NMDA (30 mg/kg sc) was administered to
      16- and 30-day-old female rats pretreated with EP. NMDA administration induced
      increases in plasma LH concentration that were 13.6-fold and 94.5-fold higher,
      respectively, than those found after NMDA alone. The increase of LH levels
      induced by NMDA was accompanied by a significant enhancement of the content of
      GnRH in the anterior and preoptic hypothalamic areas and in the medial basal
      hypothalamus (APOA/MBH). EP potentiated this increase of GnRH induced by NMDA.
      NMDA increased plasma FSH levels at 16 days of age, and this increase was
      inhibited by EP treatment. In 30-day-old rats EP induced FSH release in response
      to NMDA. This release was not observed in rats treated only with NMDA. In 16-day
      old rats EP induced an increase in the concentrations of aspartate, glutamate,
      and glycine in the anterior and preoptic hypothalamic areas and in the medial
      basal hypothalamus, the excitatory amino acids involved in NMDA
      neurotransmission. This effect was not observed in rats of 30 days of age. In
      summary, the present results show that during sexual maturation ovarian steroids
      potentiated the LH-releasing response to NMDA probably by acting at the
      hypothalamic level; furthermore, during sexual maturation there are changes in
      the response to EP of the hypothalamic concentrations of excitatory amino acids.
      These findings could be related to the neuroendocrine mechanisms regulating the
      onset of puberty and the sexual cycle in female rats.

PMID- 1347008
TI  - Pyridostigmine-mediated growth hormone release: evidence for somatostatin
      involvement.
AB  - Pyridostigmine (PD), a cholinesterase inhibitor, has been shown to elicit GH
      release when given alone and to potentiate the GH response to GH-releasing
      hormone (GHRH) in man. Numerous experiments have indirectly indicated that
      somatostatin (SS) inhibition is its likely mechanism of action. This study sought
      to establish the ability of PD to induce GH release in the rat, determine the
      dose-response relationship, and test the hypothesis that SS inhibition is the
      method of action. Three experiments were performed to monitor the GH response to
      PD. I) Five groups of male rats were food deprived for 72 h. The groups were then
      treated iv with saline, SS antibody (SS-ab), and 10, 100, and 1000 micrograms/kg
      PD, respectively. Blood samples were drawn before and after treatment. II) Two
      groups of male rats were pretreated iv with GHRH antibody (GHRH-ab) and either SS
      ab or normal sheep serum (NSS). Blood samples were drawn every 30 min for 8.5 h,
      during which time each animal was injected with PD (10 micrograms/kg) in the
      third hour and again in the sixth hour. III) Male rats received a PD injection
      (10 micrograms/kg, iv) during a spontaneous GH trough period and a second PD
      injection during a spontaneous GH peak period. Blood samples were drawn at
      regular intervals preceding and following treatments. In Exp I, PD induced a
      clear 4- to 5-fold increase in GH concentrations in food-deprived rats. The
      maximal GH responses occurred after the 10 and 100 micrograms/kg doses, although
      the pattern and duration were different with these two doses. In Exp II, PD
      induced an approximately 2-fold increase in GH values in animals pretreated with
      GHRH-ab and NSS, but failed to induce a change in GH in the animals treated with
      GHRH-ab and SS-ab. In Exp III, PD failed to induce any change in GH concentration
      when administered during spontaneous GH peaks or troughs. The first two
      experiments suggest that PD increases GH secretion in the rat via inhibition of
      SS. The failure of PD to alter GH during a spontaneous peak is consistent with
      the current hypothesis that the level of SS is low at this time. Its failure to
      alter GH during trough periods may be related to very high SS tone. In
      conclusion, our results support the hypothesis that PD acts via inhibition of SS
      secretion.

PMID- 1347009
TI  - Ontogeny of gastrin, somatostatin, and the H+/K(+)-ATPase in the ovine fetus.
AB  - In the term human and ovine fetus, plasma gastrin is elevated, but gastric acid
      secretion is below adult levels, suggesting a developmentally related immaturity
      in gastrin and gastric acid regulation. This study investigated a number of
      elements of the gastric acid regulatory system: gastrin and its glycine-extended
      precursor, somatostatin, and the H+/K(+)-ATPase. Measurements were made in blood,
      antrum, and fundus of the ovine fetus during the last half of gestation, of 15
      day-old lambs, and of adult sheep at the level of mRNA synthesis, tissue storage,
      and secretion. Plasma amidated gastrin (gastrin-amide) was elevated at or above
      adult values from 125 days (term is 145 days) and steadily increased with
      development, peaking in the lamb. Similar changes occurred with plasma glycine
      extended gastrin (gastrin-gly). The peak concentration of antral gastrin-amide
      was present in the lamb, while the maximum antral gastrin-gly level occurred 1
      week before birth. Gastrin mRNA paralleled the changes in antral gastrin-gly. The
      proportion of higher mol wt species of gastrin decreased during gestation in both
      plasma and antrum. Low amounts of mRNA for the H+/K(+)-ATPase was present from at
      least 120 days of gestation and antedated gastric acid secretion. However, there
      was a 3-fold increase in H+/K(+)-ATPase mRNA from the 140-day-old fetus to the
      lamb, the period when the greatest reduction in gastric pH occurred (pH 5 to 2).
      Antral and fundic somatostatin increased rapidly in the fetus at 120 days
      gestation and were above adult values at term and in the lamb. Somatostatin mRNA
      changed in parallel to somatostatin peptide. Somatostatin-14 was the major
      species in antrum and fundus throughout development. The increase in circulating
      and antral gastrin-amide after birth may be the result of increased amidation of
      gastrin-gly as well as increased expression of gastrin mRNA. Amidation of gastrin
      may be a regulatory step in the production of biologically active gastrin during
      development. The major increase in gastrin and the H+/K(+)-ATPase that occurs in
      the week before and after gestation correlated with the onset of increased
      gastric acidity.

PMID- 1347010
TI  - Seeding of neonatal lymph nodes by T cells and identification of a novel
      population of CD3-CD4+ cells.
AB  - Mature T cells first appear in the thymus of the mouse a few days before birth,
      about 7-8 days after the thymus was colonized by stem cells. These mature cells
      are exported to the peripheral lymphoid organs beginning at about the time of
      birth, but because the number is very small at this stage, little is known about
      the phenotype or function of these early emigrants. We have examined the cells
      that accumulate in the peripheral lymph nodes (LN) during the first week of life
      to understand better the initial seeding of the periphery by T cells. Our studies
      showed that a high proportion of neonatal LN cells were CD4+, but that the
      majority of these were CD3- during the first few days of life. The CD3-
      population did not increase greatly in number after birth and rapidly diminished
      in proportion as the number of CD3+ cells increased. These CD3-CD4+CD8- cells
      were found to be Thy-1loCD44+ and to lack surface expression of heat-stable
      antigen. B220 and Mac-1. They had lymphoid morphology, did not phagocytose latex,
      and did not exhibit any precursor activity for cells of hemopoietic lineages.
      Their origin (intra- or extrathymic) as well as their function and physiological
      role, therefore, remains unknown. CD3+ T cells, both CD4+CD8- and CD4-CD8+, were
      present in low numbers during the first 1-2 days of life, but at post-natal day
      3, a sharp increase in the accumulation of these cells occurred in both LN and
      spleen. By day 3 the CD4:CD8 ratio in LN was about 2:1, as in the adult. Crude
      estimates of the rate of export from the thymus from day 3 onwards gave values
      around 1% of thymocytes per day, i.e. close to our previous estimates for young
      adult thymus. We found no evidence of particularly high levels of emigration from
      the thymus during the first week after birth. Both CD4+CD8- and CD4-CD8+ T cell
      subsets were present in the LN as early as 1 day post-natally with CD4-CD8+
      predominating among LN T cells, even though CD3+CD4+CD8- cells predominated over
      CD3+CD4-CD8+ cells in the thymus. By day 3 the ratio had changed to 2:1 (as in
      the adult). T cells, therefore, appear to emigrate from the thymus from about the
      time of birth with a dramatic increase around day 3 after birth.

PMID- 1347011
TI  - Altered course of visceral leishmaniasis in mice expressing transgenic I-E
      molecules.
AB  - Previous studies had shown that the outcome of infection with Leishmania donovani
      was exquisitely sensitive to the influence of the major histocompatibility
      complex. In this study, we have examined the course of infection in non-obese
      diabetic (NOD) and NOD-E-3 mice, the latter expressing an I-E molecule as a
      result of transgenic introduction of the wild-type Ed alpha gene. Introduction of
      this transgene significantly altered the course of infection allowing for
      enhanced parasite multiplication in the viscera from day 14 to day 28. This was
      associated with both a delayed and reduced tissue granulomatous response in NOD-E
      3 mice. In vitro, spleen cells from these mice produced equivalent levels of
      interferon (IFN)-gamma during the early phase of infection but this originated
      from populations having a different balance of T cells subsets. In NOD mice CD8+
      T cells contribute substantially to the total levels of IFN-gamma produced, but
      in transgenic mice the contribution from this subset is significantly decreased.
      This is reflected in a reduction in the proportion of Leishmania-specific CD8+ T
      cells, which could only partially be accounted for by deletion of V beta 5- and V
      beta 3-expressing CD8+ T cells in NOD-E-3 mice. This study highlights the impact
      of the introduction of a class II gene product on disease outcome and
      unexpectedly on the functional potential of CD8+ T cells.

PMID- 1347012
TI  - Engagement of major histocompatibility complex class I and class II molecules up
      regulates intercellular adhesion of human B cells via a CD11/CD18-independent
      mechanism.
AB  - We have studied the role of major histocompatibility complex (MHC) molecules in
      the regulation of intercellular adhesion of human B cells. We found that
      molecules able to bind to MHC class II molecules, such as monoclonal antibodies
      or staphylococcal enterotoxins, induced rapid and sustained homotypic adhesion of
      Epstein-Barr virus (EBV)-transformed B cell lines as well as peripheral blood B
      lymphocytes. Moreover, anti-MHC class I monoclonal antibodies also stimulated
      intercellular adherence. Adhesion induced upon MHC engagement was faster and
      stronger than that triggered by phorbol esters. It needed active metabolism, but
      divalent cations were not required. Monoclonal antibodies directed against LFA-1
      (CD11a/CD18) or its ligand ICAM-1 (CD54) did not inhibit MHC class II-induced
      homotypic adhesion of various EBV-transformed B cell lines, nor of a variant of
      the B cell line Raji expressing very low LFA-1 surface levels. Moreover, EBV
      transformed B cells from a severe lymphocyte adhesion deficiency patient, lacking
      surface CD11/CD18, also aggregated in response to anti-MHC class I or class II
      monoclonal antibodies. Together these data indicate that engagement of MHC
      molecules may transduce signals to B cells resulting in up-regulation of
      intercellular adhesion, via an LFA-1-independent mechanism. This may play a role
      in the stabilization of T cell/antigen-presenting cell conjugates at the moment
      of antigen recognition.

PMID- 1347013
TI  - A unique CD44 monoclonal antibody identifies a new T cell activation pathway.
AB  - We have identified a new T cell activation pathway mediated by the lymphocyte
      homing receptor/CD44 molecule, 8B2.5, a local monoclonal antibody (mAb), which
      recognizes two glycoproteins of 85 and 220 kDa with wide tissue distribution, is
      shown by sequential immunoprecipitations and competitive antibody-binding
      inhibition experiments with several CD44 reference mAb to recognize the CD44
      molecule. The 8B2.5 mAb, but not reference CD44 mAb, is able to induce resting
      peripheral blood lymphocytes to proliferate in the presence of phorbol esters.
      This proliferation is monocyte dependent but Fc independent and results from
      8B2.5 mAb binding to CD44 molecules both expressed by both T cells and monocytes.
      In the absence of monocytes, proliferation can be restored by solid-phase 8B2.5
      mAb, or, to a lesser extent, by adding interleukin 2. Although CD3 and CD44
      surface molecules are found physically independent, T cell activation via the
      CD44 pathway is inhibited by CD3 modulation. In addition to the direct role of
      CD44 molecules in T cell proliferation, CD44 mAb can up- or- down-regulate the
      CD3 and CD28 pathways, depending on the presence of monocytes. These results
      suggest that T cell and monocyte binding to high endothelial venule or
      extracellular matrix proteins could further promote clonal expansion of resting T
      cells migrating in certain specific anatomic sites.

PMID- 1347014
TI  - Human endothelial cells transfected by SV40 T antigens: characterization and
      potential use as a source of normal endothelial factors.
AB  - A putative role for the vascular endothelium as target for autoantibodies has
      been suggested in several autoimmune disorders and connective-tissue diseases.
      However, there are some difficulties linked to the use of cultured endothelial
      cells (EC) that limit considerably the extensive studies on the nature of
      endothelial target antigens involved. To overcome this problem, human EC, derived
      from umbilical veins, were transfected with recombinant plasmid pSV1 which
      contained the early genes of simian virus SV40. These transfected cells, called
      EC-pSV1, are able to grow without EC growth supplement and demonstrate a
      population doubling time of about 50 h. Among the EC properties, EC-pSV1 retain
      intracellular content of angiotensin-converting enzyme activity, exhibit
      constitutive production of interleukin 6 and of a growth-promoting activity on
      early passage EV, express intercellular adhesion molecule 1 (ICAM-1) and its up
      regulation by tumor necrosis factor alpha, but have lost the expression of factor
      VIII-related antigen. Moreover, EC-pSV1 express a 55-kDa antigen found on EC and
      human platelets, and presumably acting as an antibody target in some cases of non
      allergic asthma. However, at the 50-55th generation, morphological changes and
      altered growth behavior were visible. This work demonstrates that transfection of
      EC with SV40 T antigens may be of interest, particularly in areas of research
      including the study of EC targets involved in different human diseases.

PMID- 1347015
TI  - Major histocompatibility complex (MHC) control of CD4 T cell subset activation.
      II. A single peptide induces either humoral or cell-mediated responses in mice of
      distinct MHC genotype.
AB  - CD4 T cells activated in vivo in response to human collagen type IV (hCol IV)
      resemble either T helper type 1 (Th1) or Th2 cells depending on the major
      histocompatibility complex (MHC) class II genotype of the responding mice. H-2s
      mice were shown to selectively activate Th1-like cells, releasing interleukin (IL
      2 and interferon-gamma in response to hCol IV, whereas H-2b.d mice were shown to
      selectively activate Th2-like cells, releasing IL 4 and IL 5 in response to hCol
      IV. These results suggested that MHC class II regulated the type of effector
      function observed during an immune response. It was of interest to determine if
      the functional difference observed between the CD4 T cells of the two strains was
      due to the presentation of different peptides of the hCol IV molecule by the two
      MHC class II molecules. The present results demonstrate that a single peptide of
      the collagen IV molecule will elicit a Th1-like response in H-2s strains and Th2
      like responses in H-2b.d strains, as was observed when using the intact hCol IV
      molecule. Furthermore, the failure to generate Th1-like responses in H-2b.d could
      be overcome by increasing the dose of this peptide in vitro. Compared to H-2s,
      the Th1-like response in H-2b required 100 times the amount of peptide to
      reelicit an equivalent response. These data suggest that a single peptide of hCol
      IV can control the type of effector response observed.

PMID- 1347016
TI  - Protection from lethal graft-vs.-host disease by donor stem cell repopulation.
AB  - Graft-vs.-host reaction (GVHR) induced in non-irradiated F1 mice with DBA/2J
      parental spleen and lymph node (LN) cells usually does not lead to acute GVH
      disease (GVHD). This contrasts with the GVHR induced in other parent-F1
      combinations involving both major histocompatibility complex (MHC) class I and
      class II differences between donor and host. Most signs of acute GVHD in non
      irradiated F1 mice relate to immunodeficiency following destruction of the
      lymphohemopoietic system of the host, which leads to wasting and death due to
      infections. This sequence of events is prevented when donor lymphoid cells,
      originating from grafted stem cells, repopulate the destroyed lymphohemopoietic
      system of the host. To examine whether a "silent" repopulation of the F1 host by
      donor stem cells might underly the absence of clinical signs of acute GVHD when
      GVHR is induced with DBA/2J lymphoid cells, GVHR was induced with LN cells, which
      do not contain stem cells. Indeed, GVHR induced in (C57BL/10 x DBA/2J)F1 (BDF1)
      mice with 80 x 10(6) DBA/2J LN cells led to acute GVHD. Signs of acute GVHD such
      as wasting and death did not occur when donor stem cells, from an inoculum of
      DBA/2J spleen and LN cells, were allowed to repopulate the lymphohemopoietic
      system of the host. The effect of donor stem cells on clinical signs of acute
      GVHD was more apparent when (B10.D2 x DBA/2J)F1, instead of DBA/2J, lymphoid
      cells were used to induce GVHR. The detection of alloreactive anti-host cytotoxic
      T lymphocyte (CTL) activity during acute GVHD induced with DBA/2J donor lymphoid
      cells supports the hypothesis that such CTL contribute to the destruction of the
      host immune system in acute GVHD.

PMID- 1347017
TI  - Differential sensitivity of freshly isolated and cultured murine Langerhans cells
      to ultraviolet B radiation and chemical fixation.
AB  - Previous studies have demonstrated that low doses of ultraviolet B (UVB)
      radiation (100 J/m2) abrogate the accessory function of freshly isolated murine
      epidermal Langerhans cells (fLC) and cause a parallel decrease in the ability of
      LC to express increased amounts of ICAM-1 (CD54) in vitro. We have subsequently
      observed that the accessory cell function of cultured LC (cLC), as assessed by
      their ability to support anti-CD3 monoclonal antibody (mAb)-induced T cell
      mitogenesis, was not inhibited by levels of UVB exposure (100 J/m2) that
      completely inhibited the function of fLC, although exposure of cLC to UVB
      radiation (100 J/m2) resulted in a decrease in the level of ICAM-1 expression on
      most cLC and a concomitant decrease in cLC survival during a subsequent 24-h
      incubation. Time course studies revealed that T cells stimulated with anti-CD3
      mAb in the presence of cLC became committed to proliferate 4-8 h after culture
      initiation, while 24-30 h of co-culture was required for irreversible T cell
      activation when fLC were utilized as accessory cells. In addition,
      paraformaldehyde (PFA)-fixed (non-viable) cLC supported anti-CD3 mAb-induced T
      cell proliferation, whereas PFA-fixed fLC were ineffective. We propose that cLC
      are functionally resistant to low doses of UVB radiation and chemical fixation
      because cLC express sufficient levels of the adhesion or co-stimulatory molecules
      [including ICAM-1 and Mac-1 (CD11b/CD18)] required to induce T cell activation.
      Conversely, fLC are sensitive to the effects of UVB radiation and chemical
      fixation because these physicochemical agents prevent acquisition of critically
      important surface molecules in culture.

PMID- 1347018
TI  - A method for quantitating motor deficits in a nonhuman primate following MPTP
      induced hemiparkinsonism and co-grafting.
AB  - This report describes a nonhuman primate model of MPTP-induced hemiparkinsonism
      and the recovery of motor function following co-grafting of adrenal medullary
      tissue and peripheral nerve into the lesioned area of the brain. A rhesus monkey
      (Macaca mulatta) trained to perform a complex, discrete-trial, operant task
      served as the subject. After behavioral performance on the task had stabilized
      and a high level of accuracy was maintained, 0.4 mg/kg MPTP was infused acutely
      via the left carotid artery to produce a marked impairment of movement of the
      right arm. Eighteen weeks later, medullary tissue from the left adrenal gland was
      grafted along with peripheral nerve into the left caudate nucleus. During the
      original baseline training condition, right- and left-hand performances were
      comparable on all dependent measures. However, right-hand performance was
      severely impaired following unilateral MPTP treatment, and left-hand performance
      was unaffected. Right-hand performance recovered only after adrenal medullary
      tissue was transplanted with peripheral nerve into the brain. Neuroanatomical
      analysis of brain tissue showed the anticipated neuronal loss in the left
      substantia nigra due to MPTP administration and evidence of adrenal medullary
      cell survival in the area of the co-graft. The data demonstrate that the rhesus
      monkey and the behavioral task developed during this study can be efficacious in
      characterizing the effects of MPTP on psychomotor function and in assessing the
      outcome of new strategies for treating Parkinson's disease.

PMID- 1347019
TI  - Genetically tailored atrial natriuretic factor-dependent guanylate cyclase.
      Immunological and functional identity with 180 kDa membrane guanylate cyclase and
      ATP signaling site.
AB  - Biochemical and immunological studies have established that one of the signal
      transducers of atrial natriuretic factor (ANF) is a 180 kDa membrane guanylate
      cyclase (180 kDa mGC), which is also an ANF receptor; obligatory in the
      transduction process is an intervening ATP-regulated step, but its mechanism is
      not known. GC alpha is a newly discovered member of the guanylate cyclase family
      whose activity is independent of the known natriuretic peptides, and the enzyme
      is not an ANF receptor. The genetically tailored GC alpha, GC alpha
      DmutGln338Leu364, however, is not only a guanylate cyclase but also an ANF
      receptor and is structurally and functionally identical to the cloned wild-type
      ANF receptor guanylate cyclase, GC-A. We now report that the ANF-dependent
      guanylate cyclase activity in the particulate fractions of cells transfected with
      GC alpha-DmutGln338Leu364 was inhibited by the 180 kDa mGC polyclonal antibody,
      and with this antibody probe it was possible to purify the 130 kDa expressed
      receptor; the hormone-dependent cyclase activity of this receptor was exclusively
      dependent upon ATP; and through site-directed mutational studies with GC alpha
      mutants, the signaling sequence that defines ATP binding site was identified. We
      thus conclude that 180 kDa mGC and the mutant protein are immunologically
      similar, both proteins are linked to the ANF signal in the generation of cyclic
      GMP synthesis; and in both the ligand binding and catalytic activities are
      bridged through a defined ATP binding module.

PMID- 1347020
TI  - PKC-independent inhibition of glutamate exocytosis by arachidonic acid in rat
      cerebrocortical synaptosomes.
AB  - In rat cerebrocortical synaptosomes, the addition of 4 beta-phorbol dibutyrate (4
      beta-PDBu) and arachidonic acid enhances and decreases, respectively, the
      glutamate release evoked by 4-aminopyridine. Pretreatment of synaptosomes with 12
      O-tetradecanoylphorbol 13-acetate (TPA) or pre-incubation with staurosporine,
      prevent the stimulatory effect of 4 beta-PDBu, but are without effect on the
      inhibitory action of arachidonic acid. Moreover, methyl arachidonate, which is
      not effective as a PKC activator, also strongly inhibits glutamate exocytosis.
      These results suggest that PKC is not involved in the inhibition of glutamate
      release by arachidonic acid.

PMID- 1347021
TI  - Thy-1 involvement in neurite outgrowth: perturbation by antibodies, phospholipase
      C, and mutation.
AB  - Thy-1 is a major cell surface protein anchored in the plasma membrane of neurons
      and lymphocytes by a covalent glyco-phosphatidyl-inositide linkage. Despite
      thorough characterization of the molecule's physicochemical properties, its
      biological function remains elusive. In this study we demonstrate that (i)
      monoclonal antibodies directed against Thy-1 are capable of enhancing neurite
      outgrowth from sympathetic neurons in culture, as well as stimulating the
      initiation of neurite sprouting from cultured adrenal chromaffin cells and PC12
      cells. This effect is not observed with monovalent, Fab antibody fragments.
      Treatment with intact antibodies also results in the shedding of Thy-1 into the
      culture medium. (ii) Treatment of chromaffin cells with phosphatidyl-inositol
      specific phospholipase C also results in an induction of neurite sprouting. The
      lipase effect can be blocked by preincubating the cells with monovalent anti-Thy
      1 Fab fragments, indicating that the outgrowth stimulation is specifically due to
      removal of Thy-1. (iii) An entirely different approach to elucidating the
      function of Thy-1 involves mutagenesis of PC12 cells. Selection for Thy-1
      deficient mutants revealed that cells lacking Thy-1 sprout neurites spontaneously
      at a very high frequency. A novel role for Thy-1 is proposed wherein the results
      of the mutant cell studies are compatible with the antibody and lipase data. Each
      of the perturbations can be viewed as releasing an inhibition that Thy-1 normally
      exerts on neurite outgrowth. We suggest that Thy-1 normally acts to stabilize
      neuronal membranes and processes, possibly through homophilic interactions.

PMID- 1347022
TI  - Thy-1 multimerization is correlated with neurite outgrowth.
AB  - Thy-1 is abundantly expressed in the vertebrate nervous system. Perturbation
      studies in vitro suggest that Thy-1 inhibits neurite outgrowth and stabilizes
      neuronal processes (N. K. Mahanthappa and P. H. Patterson. (1992). Thy-1
      involvement in neurite outgrowth: Perturbation by antibodies, phospholipase C,
      and mutation. Dev. Biol. 150,47-59). We here report that Thy-1 participates in
      several types of homophilic interactions, each with differential sensitivity to
      reduction and boiling. The relative abundance of the multimeric forms of Thy-1
      vary with the cell's ability to sprout neurites. Gel filtration chromatography of
      sympathetic neuron and PC12 cell lysates reveals that Thy-1 immunoreactivity
      appears in 25-, 45-, and 150-kDa forms. In neurons, Thy-1 immunoreactivity is
      distributed equally in all three forms, whereas in PC12 cells, the majority of
      Thy-1 immunoreactivity is found in the higher molecular weight forms. When PC12
      cells are induced to sprout neurites with NGF, the Thy-1 size distribution
      becomes identical to that of neurons. The three forms of Thy-1 immunoreactivity
      are likely to be homomultimers of Thy-1 because immunoaffinity-purified, soluble
      Thy-1 also forms complexes similar in size to those found in neuronal extracts.
      To test whether Thy-1 multimerization may occur through interactions like those
      between immunoglobulin heavy and light chains, synthetic peptides corresponding
      to candidate sites for such associations in Thy-1 were tested for their effects
      on multimerization and neurite outgrowth. One peptide increases the amount of
      monomeric Thy-1 relative to total Thy-1, and promotes outgrowth. These results
      suggest that multimeric forms of Thy-1 inhibit process outgrowth and neurite
      sprouting by stabilizing the surface membrane and/or underlying cytoskeleton.

PMID- 1347024
TI  - [Oxatomide-induced acute cholestatic hepatitis].

PMID- 1347023
TI  - Role of Glu318 and Thr319 in the catalytic function of cytochrome P450d
      (P4501A2): effects of mutations on the methanol hydroxylation.
AB  - Polar amino acids in the (putative) distal site are well conserved in P450s. For
      example, Glu318 for P450d is well conserved as either Glu or Asp for P450s, and
      Thr319 for P450d is also conserved for P450s. We have studied how mutations at
      Glu318 and Thr319 of P450d influence the catalytic activity toward methanol
      associated with the activation of O2. Catalytic activities of Glu318Asp,
      Glu318Ala, and Thr319Ala mutants toward methanol were 60, 25, and 38%,
      respectively, compared with that of the wild type. O2 consumption and NADPH
      oxidation rates of each mutants varied corresponding to the catalytic activities.
      However, surprisingly, efficiency (16-40%) of incorporated O to the substrate vs.
      consumed O2 for the Glu318Ala and Thr319Ala mutants were higher than that (9%) of
      the wild type. In addition, H2O2, which is produced from uncoupling for the wild
      type P450d, was not observed for reaction of the Glu318Ala and Thr319Ala mutants.
      It seemed that consumed O2 was partially reduced to 2 mol of H2O by 4-electron
      transfer from NADPH for the wild-type and Thr319Ala mutant. However, for the two
      Glu318 mutants, it appeared that the consumed O2 was not reduced in the same way.
      It was thus suggested that the conserved Glu318 and Thr319 of P450d are not
      essential for the activation of O2 in the methanol oxidation. Role of the water
      molecule or the methanol molecule in the catalytic function was implied.

PMID- 1347025
TI  - [Comparative effects of ricinoleic acid and senna on orocecal and oroanal transit
      time in healthy subjects. Application of the salacylazosulfapyridine method].
AB  - The appearance in plasma of sulphapyridine after oral administration of
      salicylazosulphapyridine (Salazopyrin) was shown to be useful for measuring the
      orocecal transit time in normal subjects. The purpose of this study was to use
      this method in diarrhea with accelerated intestinal transit time. A two-step
      study was performed in 12 healthy volunteers: a) under resting conditions; b) 2
      weeks later with ricinoleic acid 40 ml (n = 6) or senna 19 mg (X-Prep = 1.2 g; n
      = 6) administration. In each step, Salazopyrin (2 g) and 20 radiopaque markers
      were ingested with a 200 kcal meal (Polydiet TCM = 200 ml). The following
      parameters were determined: a) plasmatic level of sulphapyridine
      (spectrophotometry) at 30 min intervals during 12 h; b) 2-day stool frequency and
      weight; c) oro-anal transit time (passage of the first marker and half of the
      markers in stools). In one subject, no sulphapyridine level was detected after
      administration of ricinoleic acid. With senna, 2 day stool frequency and weight
      increased by 80 and 131 percent respectively: orocecal transit time decreased
      from 6.1 +/- 1.3 to 4.8 +/- 1.2 h (m +/- SD; P less than 0.01) and oro-anal
      transit time (first marker) decreased from 31.8 +/- 9.6 to 20.7 +/- 8.9 (P less
      than 0.05). With ricinoleic acid, 2 day stool frequency and weight increased by
      212 and 350 percent respectively; orocecal transit time decreased from 5.8 +/-
      1.8 to 2.2 +/- 0.7 (P less than 0.01) and oroanal transit time (first marker)
      decreased from 25.3 +/- 7.1 to 8.0 +/- 6.8 h (P less than 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1347026
TI  - [Burkitt's lymphoma of the pancreas].

PMID- 1347027
TI  - Benefit of resection of metastatic gastrinoma in multiple endocrine neoplasia
      type I.
AB  - Although gastrinoma resection is generally advocated for patients with the
      sporadic form of nonmetastatic Zollinger-Ellison syndrome, there is controversy
      regarding the surgical management of the gastrinoma among patients with multiple
      endocrine neoplasia type I (MEN-I). Using strict criteria, to date no biochemical
      cures of the Zollinger-Ellison syndrome lasting greater than 5 months have been
      achieved by gastrinoma resection among patients with MEN-I. Whereas resections of
      hepatic metastases have been performed in patients with sporadic gastrinoma, none
      have been reported among patients with MEN-I. The current report describes a
      patient with MEN-I, closely followed up for 30 years, in whom enlargement of
      pancreatic gastrinoma and development of hepatic gastrinoma was observed to occur
      over 3 years. After preoperative localization, an 80% pancreatectomy and a left
      lateral segmentectomy of the liver were performed. Sixteen months after the
      operation, secretin and calcium provocative testing showed that the patient's
      fasting gastrin and stimulated plasma gastrin concentrations were normal; also,
      results of computerized tomographic angiography, selective abdominal angiography,
      and hepatic venous sampling for gastrin after intra-arterial secretin injection
      were negative for gastrinoma. By achieving a 16-month cure of gastrinoma, this
      case shows that an aggressive surgical approach can benefit certain patients with
      gastrinoma who have MEN-I even in the presence of hepatic metastases.

PMID- 1347029
TI  - DNA patterns of Helicobacter pylori isolated from gastric antrum, body, and
      duodenum.
AB  - Biopsy specimens for culture of Helicobacter pylori were obtained from two
      different sites in the antrum, gastric body, and duodenal cap in 20 patients
      during endoscopic investigation of dyspepsia. H. pylori was identified in 64
      isolates obtained from 15 of the 20 patients. Analysis of chromosomal DNA from
      these isolates of H. pylori showed that 13 of 15 patients harbored a single
      strain of H. pylori throughout their stomach and duodenum. Two differing H.
      pylori types were found in two patients. Unique DNA patterns were shown in each
      of the 15 patients. The genetic heterogeneity of H. pylori is unexplained but it
      could be of considerable value for epidemiological studies.

PMID- 1347028
TI  - Escherichia coli enterotoxin (STa) binds to receptors, stimulates guanyl cyclase,
      and impairs absorption in rat colon.
AB  - To determine the contribution of the colon in Escherichia coli heat-stable
      enterotoxin-mediated diarrheal disease, toxin binding, guanyl cyclase activation,
      and toxin-induced water flux in the rat colon and ileum were compared. Scatchard
      analysis suggested a single class of heat-stable enterotoxin receptors with an
      affinity constant of binding of 10(9) L/mol in both colonocytes and ileocytes;
      however, the number of toxin receptors per cell was 3.5-fold greater in
      coloncytes than ileocytes (8.32 +/- 1.33 x 10(5) vs. 2.33 +/- 0.28 x 10(5)
      receptors per cell; P = 0.02). Heat-stable enterotoxin stimulated guanyl cyclase
      activation in an identical dose-dependent manner in proximal colonic and ileal
      membranes, with similar sensitivity and maximum response. Heat-stable enterotoxin
      also inhibited net water flux to a similar degree in both colon and ileum (-47.8
      vs. -48.4 microL.cm-1.h-1, respectively) at a dose of 8 nmol/L. At this dose in
      the colon, because of a higher baseline of absorption, absorption continued, but
      at a diminished level. At this dose in the ileum, heat-stable enterotoxin induced
      net secretion. These data are consistent with the concept that heat-stable
      enterotoxin-induced diarrheal disease results from a decreased absorptive
      capacity in the colon in the face of increased small intestinal fluid secretion.

PMID- 1347030
TI  - Arginine vasopressin inhibits phasic contractions and stimulates giant
      contractions in monkey colon.
AB  - Abdominal cramps and urgent defecation are common side effects of clinical doses
      of arginine vasopressin, indicating that the drug may have stimulating effects on
      colonic motor activity. Four strain-gauge transducers were implanted on the colon
      in six monkeys. A blood flow probe was fixed on the inferior mesenteric artery.
      After a 1-hour control recording, vasopressin, 0.13, 1.3, or 13.0 ng.kg-1.min-1,
      was infused intravenously for 90 minutes. The frequency of basal colonic
      contractions was reduced with increasing doses of vasopressin, but their mean
      amplitude and duration were not altered. Giant migrating contractions associated
      with defecation were initiated by the highest dose of vasopressin. Atropine had
      no effect on these giant migrating contractions but completely inhibited normal
      phasic contractions. Hexamethonium completely inhibited both giant migrating
      contractions and phasic contractions. Parasympathetic denervation of the colon
      did not inhibit giant migrating contractions initiated by vasopressin. Our
      findings suggest that the physiological concentrations of serum vasopressin
      present perioperatively may transiently inhibit spontaneous colon contractions
      but are unlikely to be the major cause of postoperative ileus. The giant
      migrating contractions initiated by vasopressin may account for the defecation
      associated with pharmacological doses of vasopressin. The initiation of giant
      migrating contractions by vasopressin may be mediated through a neural pathway.

PMID- 1347032
TI  - Altered glutamine metabolism in rat portal drained viscera and hindquarter during
      hyperammonemia.
AB  - In normal rats, muscle is the major glutamine releasing organ and gut is the
      major glutamine consuming organ. It has been suggested that enhanced muscle
      ammonia detoxification and gut ammonia production occurs during liver
      insufficiency-induced hyperammonemia. Therefore, ammonia and amino acid fluxes
      across portal-drained viscera and hindquarter, and muscle concentrations were
      measured in portacaval shunted and acute liver ischemia rats. Arterial ammonia
      and most amino acids were increased after portacaval shunting and increased
      progressively during liver ischemia, but net hindquarter ammonia uptake was not
      observed. Net hindquarter glutamine efflux was increased during portacaval
      shunting, but it decreased during liver ischemia, while muscle glutamine
      concentrations increased. The comparable net portal drained viscera glutamine
      uptake in normal and portacaval shunted rats changed during liver ischemia from
      net uptake to release, coinciding with release of most other amino acids. These
      results cast doubt on the ammonia detoxifying role of muscle during acute liver
      ischemia-induced hyperammonemia in the rat. The portal drained viscera glutamine
      release during severe hyperammonemia could be due to intestinal damage.

PMID- 1347031
TI  - The function of Gp170, the multidrug-resistance gene product, in the brush border
      of rat intestinal mucosa.
AB  - Gp170 is a transmembrane glycoprotein that is overexpressed in multidrug
      resistant tumor cells and is present in the apical plasma membrane domain of
      small intestinal mucosal cells. The function of Gp170 was studied in the small
      intestine of the rat. Jejunal and ileal brush border membrane vesicles, but not
      basolateral membrane vesicles, manifested adenosine triphosphate (ATP)-dependent
      transport of daunomycin, a substrate for Gp170, and contained a approximately 170
      kilodalton protein that reacts with anti-Gp170 monoclonal antibody. Whereas ATP
      supported daunomycin transport, nonhydrolyzable ATP analogues were ineffective.
      ATP-dependent daunomycin transport by brush border vesicles was unidirectional
      (inside to outside) and temperature dependent and was blocked by Gp170 inhibitors
      but not by taurocholate or bromsulphalein glutathione. Studies using everted
      small intestine revealed transport of rhodamine 123, a Gp170 substrate, from the
      serosal surface through the mucosa and inhibition by Gp170 inhibitors. These
      results suggest that Gp170 in rat small intestinal brush border membrane vesicles
      is an ATP-dependent efflux pump responsible for the transport of Gp170 substrates
      into the small intestinal lumen. Gp170 may protect against exogenously derived
      potentially damaging hydrophobic cations and contribute to the rarity of small
      intestinal cancer in humans and many animals.

PMID- 1347034
TI  - [Trapidil--a new alternative in ischemic heart disease. Report from the
      International Trapidil Workshop. Munich, 28-29 June 1991].

PMID- 1347035
TI  - [Chronic epigastric complaints: diagnosis and therapy. Stomach irritability,
      reflux, experimental therapy. Report from the European Digestive Disease Week,
      Amsterdam, 20-26 October 1991].

PMID- 1347033
TI  - Structure of the Bombyx mori fibroin light-chain-encoding gene: upstream sequence
      elements common to the light and heavy chain.
AB  - Two overlapping genomic clones containing the fibroin light-chain (Fib-L)
      encoding gene (Fib-L) were obtained from the cosmid library of the silkworm,
      Bombyx mori J-139, by hybridization with the Fib-L cDNA clone. Sequencing of the
      14.6-kb region revealed that Fib-L was 13,472 bp long containing seven exons, and
      that the gene contained a large first intron which occupied about 60% of the
      gene. Comparison of restriction patterns of the J-139 Fib-L with those of eight
      other B. mori breeds producing normal-level fibroin demonstrated that
      considerable restriction-fragment length polymorphisms were present in regions
      containing the first intron and the 3'-flanking sequence. However, sizes of the
      Fib-L mRNA and the Fib-L polypeptide were very similar among the nine breeds
      tested, suggesting that the exon sequences and the splice signals were all well
      conserved. 5'-Flanking regions of Fib-L and the fibroin heavy-chain (Fib-H)
      encoding gene (Fib-H) compared in this study contained three 18-30-bp sequences
      of high similarity and many 8-10-bp common elements, six of which coincided with
      the binding sites of homeodomain proteins. Gel retardation assays with the
      nuclear extracts of the posterior and middle silk glands suggested that protein
      factors present in the posterior silk-gland nuclei could bind to a set of those
      common upstream elements.

PMID- 1347036
TI  - Correlation of L-myc RFLP with metastasis, prognosis and multiple cancer in lung
      cancer patients.
AB  - For further study of the correlation of L-myc restriction-fragment-length
      polymorphism (RFLP) and metastasis of lung cancer to lymph nodes or other organs
      at the time of surgery, L-myc RFLP was analyzed in 252 Japanese lung-cancer
      patients. A close correlation between L-myc RFLP and metastasis was confirmed in
      this large number of patients (p = 0.01). The correlation was particularly
      pronounced in cases of adenocarcinoma and squamous-cell carcinoma. Poor prognosis
      (additional metastases after surgery) was observed in lung-cancer patients with L
      S (identified as long and short bands produced with EcoRI) and S-S type L-myc
      RFLP. In addition, the death rate of lung-cancer patients with the L-S and S-S
      types was greater than that of those with the L-L type. Lung-cancer patients of
      the L-S and S-S types had almost 4 times higher incidence of multiple cancer in
      the lung, pharynx and other organs than those with the L-L type. Our results
      indicate that, in patients with lung cancer, genetic disposition with respect to
      the L-myc gene influences the extent of metastasis, the incidence of multiple
      cancers and prognosis.

PMID- 1347037
TI  - SDZ PSC 833, a non-immunosuppressive cyclosporine: its potency in overcoming P
      glycoprotein-mediated multidrug resistance of murine leukemia.
AB  - Cyclosporin A (CsA, Sandimmune) is known to reverse P-glycoprotein (P-gp170)
      mediated multidrug resistance as efficiently as other prototype compounds of
      resistance modifiers. The immunosuppressive activity and nephrotoxicity of CsA,
      however, may limit its clinical use. PSC-833, a new cyclosporine, exerts a
      similar resistance-modifying activity but lacks toxicity or immunosuppressive
      activity. We have tested its potency in vitro and in vivo on the L1210 leukemia
      cell line transfected with a full-length cDNA copy of the human mdr I gene, which
      showed a stable 30-fold resistance towards adriamycin as compared to the parental
      cell line. In vitro growth of the transfected cell was unchanged. In vivo growth
      was less aggressive; the survival time of inoculated mice was prolonged. In
      vitro, PSC-833 was at least as potent as CsA or verapamil in reversing multidrug
      resistance. In vivo, the drug-resistant L1210 leukemia was completely
      unresponsive to i.v. monotherapy with adriamycin at its maximum tolerated dose
      (MTD). PSC-833 enhanced the activity and toxicity of adriamycin. The MTD of
      adriamycin was about 3 times lower than when given alone. On this basis, the MTD
      of i.v. adriamycin in combination with oral PSC-833 successfully overcame
      refractoriness to treatment. Survival times of the mice were considerably
      prolonged and even some cures of leukemic mice occurred.

PMID- 1347038
TI  - [How is bowel function? Satellite symposium at the 19th Congress of the Society
      of Gastroenterology, 25-26 October 1991].

PMID- 1347039
TI  - Imipramine treatment of children with separation anxiety disorder.
AB  - The efficacy of imipramine was investigated in 20 children (ages 6 to 15) with
      separation anxiety disorder. Children were treated for a month with vigorous
      behavioral treatment. If they did not respond, they entered a double-blind,
      randomized, 6-week trial of imipramine or placebo. Of 45 children accepted, 21
      (47%) entered the trial. About half the children improved with either treatment,
      and no superiority for imipramine was obtained. There was no instance of
      clinically significant EKG changes. This small study failed to replicate previous
      findings of imipramine efficacy in a similar, but larger, clinical population.

PMID- 1347040
TI  - Cloning and sequence analysis of the muramidase-2 gene from Enterococcus hirae.
AB  - Extracellular muramidase-2 of Enterococcus hirae ATCC 9790 was purified to
      homogeneity by substrate binding, guanidine-HCl extraction, and reversed-phase
      chromatography. A monoclonal antibody, 2F8, which specifically recognizes
      muramidase-2, was used to screen a genomic library of E. hirae ATCC 9790 DNA in
      bacteriophage lambda gt11. A positive phage clone containing a 4.5-kb DNA insert
      was isolated and analyzed. The EcoRI-digested 4.5-kb fragment was cut into 2.3-,
      1.0-, and 1.5-kb pieces by using restriction enzymes KpnI, Sau3AI, and PstI, and
      each fragment was subcloned into plasmid pJDC9 or pUC19. The nucleotide sequence
      of each subclone was determined. The sequence data indicated an open reading
      frame encoding a polypeptide of 666 amino acid residues, with a calculated
      molecular mass of 70,678 Da. The first 24 N-terminal amino acids of purified
      extracellular muramidase-2 were in very good agreement with the deduced amino
      acid sequence after a 49-amino-acid putative signal sequence. Analysis of the
      deduced amino acid sequence showed the presence at the C-terminal region of the
      protein of six highly homologous repeat units separated by nonhomologous
      intervening sequences that are highly enriched in serine and threonine. The
      overall sequence showed a high degree of homology with a recently cloned
      Streptococcus faecalis autolysin.

PMID- 1347041
TI  - P-glycoprotein. ATP hydrolysis by the N-terminal nucleotide-binding domain.
AB  - Two ATP-binding domains are found in members of the family of ATP-dependent
      transport proteins, which includes P-glycoprotein and cystic fibrosis
      transmembrane conductance regulator. To investigate the involvement of the two
      ATP-binding domains in the ATPase activity of P-glycoprotein, full-length and the
      5'-half of human MDR1 cDNA, which encodes P-glycoprotein, were fused with the
      Escherichia coli lacZ gene and expressed in NIH3T3 cells. Immunoprecipitated full
      length P-glycoprotein beta-galactosidase showed ATPase activity with apparent
      specific activity of 180 nmol/mg/min, a value higher than previously reported, in
      the presence of phospholipids, suggesting that stabilization of the transmembrane
      domains is necessary for ATP hydrolysis. N-terminal half P-glycoprotein-beta
      galactosidase also showed ability to hydrolyze ATP but with slightly lower
      specific activity. Both ATPase activities showed similar characteristics when the
      effect of several inhibitors was analyzed, indicating that the N-terminal ATP
      binding domain contains all residues necessary to hydrolyze ATP without
      interacting with the C-terminal ATP-binding domain.

PMID- 1347042
TI  - Tyrosine phosphatase inhibition permits analysis of signal transduction complexes
      in p185HER2/neu-overexpressing human tumor cells.
AB  - The HER2/neu gene encodes a receptor tyrosine kinase that is highly homologous to
      the epidermal growth factor receptor. Overexpression of the receptor in mammary
      and ovarian carcinoma correlates with poor patient prognosis. To determine how
      the overexpression of a normal receptor leads to the generation of an oncogenic
      signal, we compared the patterns of tyrosine phosphorylation in tumor-derived
      human cell lines expressing high levels of p185HER2/neu. In intact SKBR3 cells,
      basal phosphorylation of p185HER2/neu was not detected. However, pretreatment of
      cells with the tyrosine phosphatase inhibitor, sodium orthovanadate, led to the
      detection of phosphotyrosine on phospholipase C-gamma (PLC-gamma), GTPase
      activating protein but not on the RAF-1 kinase. Strikingly, PLC-gamma was
      detected in a complex which contained multiple tyrosine-phosphorylated
      polypeptides. This complex was detected only in cytoplasmic fractions and had a
      distinct composition in different p185HER2/neu-overexpressing cell lines.
      Although GTPase-activating protein has been found previously in association with
      proteins of 190 and 62 kDa in fibroblasts, in SKBR3 cells it was found associated
      with multiple additional tyrosine-phosphorylated polypeptides. These experiments
      show that SKBR3 cells possess high levels of protein tyrosine phosphatase that
      can act upon p185HER2/neu. Moreover, they reveal, for the first time, the
      presence of PLC-gamma and GTPase-activating protein in cytosolic complexes
      containing a variety of other tyrosine-phosphorylated polypeptides. These
      observations suggest novel possibilities for the specific definition of receptor
      generated signals in tumor cells.

PMID- 1347043
TI  - Dipeptidyl peptidase IV (CD 26) gene expression in enterocyte-like colon cancer
      cell lines HT-29 and Caco-2. Cloning of the complete human coding sequence and
      changes of dipeptidyl peptidase IV mRNA levels during cell differentiation.
AB  - A cDNA (DPCR1) specific for human intestinal dipeptidyl peptidase IV (DPP IV) has
      been isolated. This 1.7-kilobase cDNA, together with a previously published
      partial sequence, covers the entire open reading frame of human DPP IV plus 67
      base pairs of the 3'-untranslated end. Human DPP IV is a 766-amino acid
      polypeptide with a high degree of homology with the rat liver protein. The
      characterization of this molecular probe allowed us to definitively confirm the
      identity of DPP IV with CD 26, a mouse thymocyte activation antigen, a conclusion
      strengthened by the fact that we observed identical patterns on Southern blot of
      human genomic DNA hybridized either with human DPP IV or mouse CD 26 cDNA probe.
      Using this new tool, we have investigated the expression of DPP IV during the
      onset of enterocytic differentiation of two cultured human colon cancer cell
      lines, HT-29 and Caco-2. Whatever the cell line and the culture conditions, DPP
      IV expression strictly correlates with the presence of a differentiated
      phenotype, as shown by enzyme activity and the steady state amount of the protein
      measured by indirect immunofluorescence and Western blot. Accordingly, DPP IV
      biosynthesis exclusively increases in cells that display an enterocytic
      differentiation. Neither the glycosylation nor the stability of the protein
      appear to be dependent on the state of enterocytic differentiation. The DPP IV
      mRNA level remains very low in undifferentiated cell populations and specifically
      increases in cells that undergo an enterocytic differentiation. These results
      strongly suggest that DPP IV gene expression is controlled at the transcriptional
      or posttranscriptional level during intestinal differentiation.

PMID- 1347044
TI  - Expression of the human multidrug resistance cDNA in insect cells generates a
      high activity drug-stimulated membrane ATPase.
AB  - Drug-resistant tumor cells actively extrude a variety of chemotherapeutic agents
      by the action of the multi-drug resistance (MDR1) gene product, the plasma
      membrane P-glycoprotein. In this report we show that the expression of the human
      MDR1 gene in cultured Sf9 insect cells via a baculovirus vector generates a high
      activity vanadate-sensitive membrane ATPase. This ATPase is markedly stimulated
      by drugs known to interact with the P-glycoprotein, such as vinblastine and
      verapamil, and the ability of the various drugs to stimulate the ATPase
      corresponds to their previously observed affinity for this transporter. The drug
      stimulated ATPase is not present in uninfected or mock-infected Sf9 cells, and
      its appearance correlates with the appearance of the MDR1 gene product detected
      with a monoclonal anti-MDR protein antibody and by labeling with 8-azido-ATP. The
      drug-induced ATPase requires magnesium ions, does not utilize ADP or AMP as
      substrates, exhibits a half-maximal activation at about 0.5 mM MgATP, and its
      maximal activity (about 3-5 mumol/mg MDR protein/min) approaches that of the well
      characterized ion transport ATPases. These results provide the first direct
      demonstration of a high capacity drug-stimulated ATPase activity of the human
      multidrug resistance protein and offer a new and simple assay for the
      investigation of functional interactions of various drugs with this clinically
      important enzyme.

PMID- 1347045
TI  - 20th National Cancer Congress of the German Cancer Society. Berlin, 16-20 March
      1992. Abstracts.

PMID- 1347046
TI  - Glutamine and glutamate metabolism in normal and heat shock conditions in
      Drosophila Kc cells: conditions supporting glutamine synthesis maximize heat
      shock polypeptide expression.
AB  - We have previously reported that Drosophila Kc cells require glutamine for
      maximal expression of heat shock proteins in stressed conditions (Sanders and
      Kon: J. Cell. Physiol. 146:180-190, 1991). The mechanism of this effect has been
      investigated by comparing the metabolic utilization of glutamine in conditions
      which support hsp expression with that of glutamate in conditions where up to 100
      fold less hsp is synthesized. This comparison showed that free ammonia was
      generated by cells incubated in the presence of glutamine in 37 degrees C (heat
      shock) conditions, but not at 25 degrees C, and not in the presence of glutamate
      in either normal or heat shock conditions. There was no difference in the amount
      of [14C]O2 generated from either [14C]-labeled amino acid in the tricarboxylic
      acid cycle, but three- to four-fold more alanine was synthesized in cells
      incubated in glutamine than in glutamate. Treating the cells with
      aminotransferase inhibitors to artificially increase NH3 release raised hsp
      expression in the presence of glutamate to maximal levels characteristic of
      glutamine. This potentiation correlated with inhibition of alanine
      aminotransferase. Since only NH3 production correlated with hsp expression in
      heat shock conditions in the presence of glutamine, and NH3 addition to glutamate
      also resulted in maximal hsp expression, we measured glutamine production in
      glutamate plus NH3 and observed net glutamine synthesis. The supposition that
      glutamine itself is responsible for the regulatory changes supporting maximal hsp
      expression was supported by the finding that the glutamine analog, 6-diazo-5-oxo
      L-norleucine (DON), mimicked the effects of glutamine. We conclude that glutamine
      imposes regulatory changes which alter nitrogen metabolism and support hsp
      expression in Kc cells.

PMID- 1347047
TI  - Sensitivity and specificity of a recombinant transmembrane glycoprotein (rgp21)
      spiked western immunoblot for serological confirmation of human T-cell
      lymphotropic virus type I and type II infections.
AB  - Serum specimens (n = 2,712) obtained from individuals residing in diverse
      geographic regions and categorized as seropositive (n = 122), seroindeterminate
      (n = 523), or seronegative (n = 2,067) for human T-cell lymphotropic virus (HTLV)
      infection in accordance with U.S. Public Health Service guidelines were retested
      by recombinant transmembrane protein (rgp21)-spiked Western immunoblotting. Of
      the 122 HTLV-positive specimens, those from 85 of 85 (100%) U.S. blood donors, 2
      of 2 (100%) Brazilians, 1 of 2 (50%) Indonesians, 14 of 14 (100%) Solomon
      Islanders, and 18 of 19 (95%) Papua New Guineans reacted with rgp21, yielding an
      overall sensitivity of 98% (120 of 122). Specimens from individuals whose
      infections were confirmed to be HTLV type I or HTLV type II by the polymerase
      chain reaction assay reacted equally well with rgp21. Of the 523 HTLV
      indeterminate specimens, those from 21 of 379 (5.5%) U.S. blood donors, 3 of 6
      (50%) Brazilians, 10 of 23 (44%) Ugandans, 8 of 49 (16%) Indonesians, 4 of 36
      (11%) Solomon Islanders, and 5 of 30 (17%) Papua New Guineans reacted with rgp21.
      None of these 51 specimens reacted with native gp46 and/or gp61/68 in a
      radioimmunoprecipitation assay, suggesting a false-positive reaction (9.75%). Of
      the 2,067 HTLV-negative specimens, 12 reacted with rgp21, yielding a false
      positivity rate of 0.6%. These data indicate that while detection of rgp21 is
      highly sensitive, it can yield false-positive results. Thus, specimens exhibiting
      reactivity with rgp21 in the absence of reactivity with native gp46 and/or
      gp61/68 by Western blot should be tested further by a radioimmunoprecipitation
      assay to verify HTLV type I or type II infection.

PMID- 1347048
TI  - Evidence for functional heterogeneity of rat CD4+ T cells in vivo. Differential
      expression of IL-2 and IL-4 mRNA in recipients of cardiac allografts.
AB  - The in vivo relevance of functional dichotomy of CD4+ Th clones was studied by
      analyzing the induction of mRNA encoding for Th1- (IL-2) and Th2- (IL-4) specific
      lymphokines in a model of accelerated (24 h) cardiac allograft (Tx) rejection in
      presensitized rats. The polymerase chain reaction-assisted screening of total
      cellular RNA from cardiac Tx of otherwise untreated sensitized recipients has
      revealed sequential lymphokine mRNA expression, with the peak of IL-2 mRNA (6-12
      h) preceding that for IL-4 mRNA, which was maximal at the time of actual Tx loss
      (24 h). Both IL-2 and IL-4 transcripts could be readily detected by polymerase
      chain reaction analysis in the spleens during the course of accelerated
      rejection. Treatment of prospective cardiac Tx recipients with BWH-4, a mouse
      anti-rat CD4 mAb, abrogated rejection at 24 h and prolonged cardiac Tx survival
      to ca. 11 days, coinciding with significantly diminished IL-2 mRNA expression. In
      contrast, CD4 targeted therapy preserved intra-Tx and splenic transcription of
      the IL-4 gene. Spleen lymphocytes from mAb-conditioned recipients separated by
      magnetic microspheres into phenotypically distinct subpopulations, showed
      differential induction of IL-2 and IL-4 mRNA. Thus, IL-2 mRNA was at most very
      weakly expressed, whereas IL-4 transcription was strongly induced both in CD4+ T
      cells and its OX-22- subset. This study demonstrates the induction of IL-4 mRNA
      in situ in the rat system, describes discordant elaboration of IL-2 and IL-4 mRNA
      in untreated/anti-CD4 mAb-treated cardiac Tx recipients, and identifies OX-22-
      CD4+ T cells as the IL-4 mRNA producers. Thus, these results provide evidence for
      functional heterogeneity of rat CD4+ T cells in vivo, as defined by divergent
      mRNA lymphokine transcription profiles.

PMID- 1347049
TI  - Identification of IL-7-dependent bone marrow-derived Thy-1-B220- lymphoid cell
      clones that rearrange and express both Ig and T cell receptor genes.
AB  - Bone marrow stromal cell lines and lymphoid cell lines were co-established from
      the Whitlock-Witte type of long term liquid cultures of MRL/1 and C57BL/10 (B10)
      (Thy-1.1) bone marrow cells. The present study investigates the immunologic
      nature of parental and cloned lymphoid cell lines. Both strains of parental lines
      and their clones did not grow alone but proliferated on the monolayers of co
      established parental stromal cell lines from a syngeneic or alternative strain.
      When various lymphokines or cytokines were tested for their capacity to support
      the growth of these lymphoid cell clones, only IL-7 could substitute for the
      growth-promoting function of stromal cells. These IL-7-dependent clones expressed
      neither Thy-1 nor B220 Ag. However, all of them from two strains were found to
      rearrange synchronously H chain of Ig as well as gamma chain of TCR genes. Some
      of the clones transcribed a mature size of IgH mRNA. Co-expression of mRNA for
      lambda 5 but not for IgL chain (kappa, lambda) genes resulted in the generation
      of cell surface mu chain in these clones. Other clones expressed a smaller size
      of IgH mRNA without exhibiting surface mu chain. Irrespective of the differences
      in IgH rearrangements and its mRNA expression, a mature size TCR gamma mRNA was
      detected in all of the clones. Thus, these results demonstrate the existence of
      untransformed (IL-7-dependent) immature lymphoid cells rearranging both Ig and
      TCR genes. Their unique features concerning cell surface markers (B220- mu+),
      specific growth factor requirement, and various modes of Ig/TCR gene
      rearrangements are discussed in the context of early lymphoid development.

PMID- 1347050
TI  - Regulation of ICAM-1 expression and function in human dermal fibroblasts by IL-4.
AB  - ICAM-1 is found on the surface of many hematopoietic and nonhematopoietic cells
      and can function as an adhesive ligand for the integrin, leukocyte function
      associated molecule-1 (LFA-1, CD11a/CD18). ICAM-1/leukocyte function-associated
      molecule-1 interaction has been shown to be of importance in many immune-mediated
      cell-cell adhesion reactions. In vitro, unstimulated human fibroblast cell
      cultures express low levels of ICAM-1. Using ELISA, cytofluorography, electron
      microscopy, Northern analysis, and an in vitro cell adherence assay, we
      demonstrate that treatment of human dermal fibroblasts with the cytokine IL-4
      leads to an increase in cell surface ICAM-1 expression that is under
      transcriptional control as well as increased fibroblast adhesion to LFA-1-bearing
      T lymphocytes. The kinetics of increased ICAM-1 expression induced by IL-4
      paralleled the increase in ICAM-1-dependent T lymphocyte adhesion. The increase
      in T cell adhesion was determined to be due to the effects of IL-4 on the
      fibroblasts and not the adhering T cells. Treatment of fibroblasts with IL-4 also
      resulted in enhanced binding of human rhinovirus, a recently reported additional
      ligand for ICAM-1. Virus binding was IL-4 dose dependent and could be inhibited
      with mAb to ICAM-1. Both the expression of ICAM-1 and the ICAM-1-dependent
      increase in T lymphocyte adhesion that was induced by IL-4 could be inhibited by
      preexposure of the fibroblasts to either IL-1 or IL-6, suggesting that multiple
      cytokines can have both positive and negative effects on human fibroblast ICAM-1
      expression and function.

PMID- 1347051
TI  - Pertussis toxin-induced lymphocytosis is associated with alterations in thymocyte
      subpopulations.
AB  - Pertussis toxin (Ptx), an important adjuvant for inducing certain organ-specific
      autoimmune diseases in mice, exerts multiple effects upon the immune system. In
      addition to its adjuvant effects, which include enhancement of delayed-type
      hypersensitivity and increased antibody production. Ptx elicits a marked
      lymphocytosis with a concomitant decrease in thymic weight. In vitro studies
      indicate that Ptx acts directly on thymocytes and that both susceptible and
      resistant populations exist. It is believed that these susceptible cells are
      released into the circulation and account, in part, for the T cell component of
      the lymphocytosis. We have used flow cytometry to analyze the CD4, CD8, and Thy-1
      phenotypes of thymic and peripheral T cells from Ptx-treated mice. In the thymus,
      there is a dramatic decrease in the number of CD4+CD8+ (double positive) cells at
      all doses tested (0.25, 0.50, and 1.0 microgram) by day 4 after Ptx treatment.
      The double negative and single positive populations remain relatively constant.
      Analysis of Thy-1 expression reveals a significant reduction in Thy-1hi
      thymocytes, with little change in the Thy-1lo population. Thus Ptx primarily
      affects and depletes, in a dose-dependent fashion, thymic T cells with an
      immature phenotype. These results mimic those of corticosteroids, although
      neither prior adrenalectomy nor treatment with the antiglucocorticoid RU486 are
      able to prevent the effects of Ptx. In the periphery of Ptx-treated animals, the
      relative increase in the number of CD4+ T cells is more than that of CD8+ T
      cells. Double positive and Thy-1hi cells cannot be detected in appreciable
      numbers. These results are consistent with the concept that Ptx may drive
      immature thymocytes through accelerated maturation for release into the periphery
      as single positive, predominantly CD4+, Thy-1lo cells. Increased numbers of such
      cells may in part account for the immunopotentiating effects of Ptx, particularly
      as they relate to the induction of organ-specific autoimmune disease. Treatment
      with purified Ptx beta-oligomer fails to elicit any of the responses described
      above, indicating that the holotoxin is required for such activities.

PMID- 1347052
TI  - A method of preparing blood leucocytes for flow cytometry which prevents
      upregulation of leucocyte integrins.
AB  - LeuCAM (CD11/CD18) cell-surface antigens are easily upregulated on cell
      manipulation ex vivo. A procedure for preparing leucocytes, in which human blood
      is immediately treated ex vivo with buffered formaldehyde and then the
      erythrocytes and platelets are removed by lysis and differential centrifugation,
      has been successfully applied to the analysis of LeuCAM antigen expression by
      flow cytometry. We show that the increased expression of monocyte CD11/CD18,
      which occurs when mononuclear leucocytes are separated by a standard Lymphoprep
      density gradient separation, can be avoided if cells are fixed immediately.
      Following this fixation polymorphs are unable to upregulate CD11/CD18 in response
      to fMLP stimulation in vitro. The technique produces lymphocyte, polymorph and
      monocyte populations that can be clearly defined on the basis of forward scatter
      and side scatter, and preserves the expression of various surface antigens; the
      percentages of gated lymphocytes expressing CD3, CD4, and CD8 were similar to
      those obtained using a commercial fixing and lysis solution. The processing does
      not render cells permeable to antibodies, as evidenced by our failure to stain
      cells with antibodies to intracellular antigens. We believed the method to be
      useful for measuring CD11/CD18 expression on blood leucocytes from normal or
      pathological specimens and to have application to the measurement of other cells
      surface antigens which may also be upregulated by the separation procedures.

PMID- 1347053
TI  - Dehydroepiandrosterone as predictor for progression to AIDS in asymptomatic human
      immunodeficiency virus-infected men.
AB  - The steroid hormone dehydroepiandrosterone (DHEA) has been reported to protect
      against certain viral infections in animal models and to be a modest inhibitor of
      human immunodeficiency virus type 1 (HIV-1) infection in vitro. Serum DHEA levels
      were determined in 41 asymptomatic HIV-1-seropositive subjects, who progressed to
      AIDS within 5 years after entering a cohort study, in 41 HIV-1-seropositive
      controls, who remained asymptomatic, and in 41 HIV-1-seronegative controls. At
      entry, DHEA levels were higher in the seronegative group (median, 13.3 nmol/l)
      than in either the seropositive nonprogressors (median, 9.2 nmol/l; P = .01) or
      the progressors (median, 7.2 nmol/l; P less than .001). DHEA levels in the
      progressors approximately 5 months before the diagnosis of AIDS were lower than
      the levels in the nonprogressors after the same follow-up (median, 5.6 vs. 8.8
      nmol/l; P = .007). DHEA levels less than 7 nmol/l and CD4+ cell counts less than
      0.5 x 10(9)/l both proved to be independent predictors for disease progression in
      HIV-1-infected men.

PMID- 1347054
TI  - Viral phenotype and immune response in primary human immunodeficiency virus type
      1 infection.
AB  - Nineteen individuals were studied for virologic and immunologic events during
      primary human immunodeficiency virus type 1 (HIV-1) infection. In 16 individuals
      only non-syncytium-inducing (NSI) isolates were detected; syncytium-inducing (SI)
      isolates were obtained from 3. Studies of transmitter-recipient pairs indicated
      that both NSI variants and SI variants were transmitted and that SI variants may
      be suppressed in the recipient. CD4+ T cells remained in the normal range in 15
      of 16 individuals with NSI isolates but rapidly declined in all 3 individuals
      with SI variants, 1 of whom was treated with zidovudine. The most marked increase
      in CD8+ T cells and activated CD8+ T cells was observed in individuals with the
      most pronounced clinical signs of acute HIV-1 infection. Activated CD8+ T cells
      were only transiently elevated in individuals with SI variants, suggesting that
      an impaired cellular anti-HIV-1 immune response plays a role in the rapid
      progression to AIDS.

PMID- 1347055
TI  - Effect of pili-specific antibodies on the adherence of Haemophilus influenzae
      type b to human buccal cells.
AB  - Different strains of Haemophilus influenzae type b (Hib) produce antigenically
      distinct pili that mediate adherence to human buccal epithelial cells. This study
      determined the ability of antibodies specific for the LKP3 pili of Haemophilus
      influenzae type b to inhibit the adherence of Hib strain Eagan (p+). Antiserum
      was prepared by immunization of rabbits with pili purified from Hib strain Eagan
      (p+). The presence of pili-specific antibodies in the immune serum was shown by
      selective immunoprecipitation of pilin and by electron microscopy of cells
      labeled with immunogold. Immune serum, affinity-purified antibody, and Fab
      fragments from immune serum significantly inhibited (P less than .001) adherence
      of strain Eagan (p+) to human buccal epithelial cells whereas preincubation with
      preimmune rabbit serum or Fab fragments from preimmune serum had no significant
      effect on adherence. Dilution of the immune serum, affinity-purified antibodies,
      or Fab fragments from immune serum resulted in decreased inhibition of Hib
      adherence. These results indicate that antibodies specific for LKP3 pili can
      effectively inhibit adherence of Hib strain Eagan (p+) and probably other strains
      that express this pilus serotype.

PMID- 1347056
TI  - Virulent Treponema pallidum activates human vascular endothelial cells.
AB  - Perivascular lymphocytic infiltration, fibrin deposition, and endothelial cell
      abnormalities consistent with cellular activation are prominent histopathologic
      features of syphilis, a sexually transmitted disease caused by the spirochetal
      bacterium Treponema pallidum. Because activated endothelial cells play important
      roles in lymphocyte homing and hemostasis, the ability of virulent T. pallidum to
      activate cultured human umbilical vein endothelial cells (HUVEC) was
      investigated. T. pallidum induced the expression of intercellular adhesion
      molecule-1 (ICAM-1) and procoagulant activity on the surface of HUVEC. Electron
      microscopy of T. pallidum-stimulated HUVEC revealed extensive networks of fibrin
      strands not observed in cultures without treponemes. ICAM-1 expression in HUVEC
      also was promoted by a 47-kDa integral membrane lipoprotein purified from T.
      pallidum, implicating a role for spirochete membrane lipoproteins in endothelial
      cell activation. The combined findings are consistent with the pathology of
      syphilis and provide the first evidence that a pathogenic spirochetal bacterium
      such as T. pallidum or its constituent integral membrane lipoprotein(s) can
      activate directly host vascular endothelium.

PMID- 1347057
TI  - Immunologic markers of clinical evolution in children recently infected with
      Leishmania donovani chagasi.
AB  - The study attempted to identify immunologic markers for progression of Leishmania
      donovani chagasi infection to disease in children in an area endemic for visceral
      leishmaniasis (VL). [3H]thymidine uptake of lymphocytes stimulated with L.
      donovani chagasi antigen from children with asymptomatic infection (25,286 +/-
      11,648) and from children with self-healing subclinical infection (15,511 +/-
      4681) was greater (P = .001) than that observed with lymphocytes from children
      who progressed to classic VL (4811 +/- 2984). The interferon-gamma (IFN-gamma)
      levels from asymptomatic and subclinically infected children (74 +/- 90 units/ml)
      were higher (P = .02) than those observed in children who progressed to VL (7 +/-
      8 units/ml). Absence of lymphocyte blastogenesis and IFN-gamma production were
      associated with progression of infection to classic VL. In the presence of these
      markers, children should be closely followed to identify signs and symptoms that
      would permit early initiation of therapy.

PMID- 1347059
TI  - Analysis of DNA restriction fragment length polymorphism extends the evidence for
      breast milk transmission in Streptococcus agalactiae late-onset neonatal
      infection.
AB  - Analysis of restriction fragment length polymorphism (RFLP) of total DNA and of
      ribosomal DNA (ribotyping) was used to document four cases of Streptococcus
      agalactiae mother-to-infant transmission potentially associated with ingestion of
      infected mother's milk. Twenty strains were analyzed. Ten strains were mother
      baby pairs, five from the milk of five mothers, four from their neonates with
      late-onset infection, and one from a colonized neonate. All mothers had early
      postpartum mastitis. Ten unrelated strains were studied for comparison. In each
      case, the two strains of each mother-baby pair produced identical RFLP patterns
      of total DNA. The 10 unrelated strains generated 10 different patterns, one of
      which, though, was observed in one of the mother-baby pairs. Ribotyping was less
      discriminative than total DNA RFLP analysis (6 different patterns vs. 13). These
      data extend the evidence for breast milk transmission in S. agalactiae late-onset
      neonatal infection.

PMID- 1347058
TI  - Antibody to capsular polysaccharides of Streptococcus pneumoniae after
      vaccination of human immunodeficiency virus-infected subjects with 23-valent
      pneumococcal vaccine.
AB  - The Centers for Disease Control recommends that, because of a greatly increased
      susceptibility to pneumococcal infection, all persons infected with human
      immunodeficiency virus (HIV) receive pneumococcal vaccine. Using an ELISA
      specific for antibody to capsular polysaccharide, a postvaccination antibody was
      evaluated to five commonly infecting serotypes of Streptococcus pneumoniae.
      Thirty-nine HIV-infected persons with less than or equal to 500 CD4 cells
      exhibited significantly fewer responses than did healthy controls; overall, only
      46 (24%) of 195 possible responses were positive compared with 45 (75%) of 60 in
      12 HIV-infected subjects with greater than 500 CD4 cells and 92 (74%) of 125 in
      25 healthy controls (P less than .001). Subjects with less than or equal to 500
      CD4 cells responded to a mean of 1.1 antigens versus a mean of 3.8 and 3.7 in
      those with greater than 500 CD4 cells and controls, respectively (P less than
      .001). There were no differences between responses in those with less than 200
      and those with 200-500 CD4 cells. Within groups stratified by CD4 cell counts,
      further stratification by clinical status did not reveal significant differences.
      Since asymptomatic HIV-infected persons with less than 500 CD4 cells show
      abnormal responses, pneumococcal vaccine should be given when HIV infection is
      first detected.

PMID- 1347060
TI  - Disseminated Mycobacterium avium complex infection: clinical identification and
      epidemiologic trends.
AB  - To evaluate the incidence of disseminated Mycobacterium avium complex infection
      (DMAC) and to define the association between signs and symptoms and development
      of DMAC in patients with human immunodeficiency virus (HIV) infection, all cases
      of DMAC at Grady Memorial Hospital Infectious Disease Clinic (Atlanta) between
      1985 and 1990 were reviewed, and a prospective study of the association of
      symptoms with DMAC was done. Between 1985 and 1990, DMAC occurred in 16% of
      patients with AIDS. Incidence increased from 5.7% in 1985-1988 to 23.3% in 1989
      1990 (P less than .001). Median time from AIDS diagnosis to diagnosis of DMAC
      increased from 4.5 months in 1985-1988 to 8 months in 1989-1990 (P less than
      .02). In the prospective study, DMAC was seen only in persons with a CD4+ count
      less than 100 cells/mm3 and was associated with fever (P less than .03), anemia
      (P less than .001), weight loss (P less than .01), diarrhea (P less than .01),
      and elevated alkaline phosphatase (P less than .01). It is recommended that all
      such HIV-infected persons have mycobacterial blood cultures done.

PMID- 1347061
TI  - Symposium report. Biophysical aspects of Auger processes.

PMID- 1347062
TI  - Free radicals from irradiated lyophilized DNA: influence of water of hydration.
AB  - Lyophilized DNA equilibrated with water vapour at various relative humidities (0
      95% H2O or D2O) was X-irradiated at 77 K and analysed for free radicals by
      electron paramagnetic resonance (EPR) spectroscopy in the temperature range 77
      280 K. Analysis of spectra according to variation in humidity, microwave power
      and temperature generally yielded a doublet and a triplet spectrum at 77 K. The
      doublet partially converted into the 5-thymyl radical (TH.). DNA containing
      deuterated thymine (dTDNA) revealed that the doublet of 'normal' DNA should be
      composed of two similar doublets, one of which should be assigned to the thymine
      anion, the other possibly the cytosine anion. The triplet signal was more stable
      and could be related to the guanine cation or its deprotonated successor. Several
      other patterns were detected, among them an allyl radical in highly aquated DNA
      (95% humidity). Other features occurred either predominantly or exclusively in
      DNA equilibrated above 66% relative humidity and were ascribed to an influence of
      the secondary structure. Among them were components possibly indicating H- or D
      addition to the cytosine base, a reaction also derivable for dTDNA. Quantitative
      analysis of the total radical yield and the relative TH. concentration revealed
      that one cause of the dominance of the latter is its thermal stability vs. other
      species. The total radical concentration increases with target size up to 76%
      relative humidity, the hydration water forming an integral part of the DNA. At
      95% relative humidity OH. radicals are formed in addition to DNA radicals,
      showing that ice and hydrated DNA have separated into discrete targets.

PMID- 1347063
TI  - Level of DNA double-strand break rejoining in Chinese hamster xrs-5 cells is dose
      dependent: implications for the mechanism of radiosensitivity.
AB  - Rejoining of DNA double-strand breaks (dsb) was measured in a dsb repair
      deficient mutant of CHO cells, xrs-5, after exposure to various doses of X-rays
      in the range between 15 and 50 Gy. For the experiments plateau-phase cultures
      were employed and dsb assayed by a pulsed field gel electrophoresis assay, the
      asymmetric field inversion gel electrophoresis (AFIGE). The half-times of dsb
      rejoining were larger in xrs-5 than in parental CHO cells and increased in both
      cell lines with increasing dose of radiation. The fraction of dsb remaining
      unrejoined after 240 min incubation at 37 degrees C was also higher in xrs-5 than
      in CHO cells, but decreased with decreasing dose of radiation. Although a
      decrease in the fraction of unrepaired dsb with decreasing dose has also been
      reported for repair-proficient cell lines, the extent of the phenomenon and its
      dependence on dose are entirely different in xrs-5 cells. We propose that this
      decrease in the fraction of unrejoined dsb with decreasing dose of radiation
      derives from the genetic alterations underlying the increased sensitivity to
      radiation of xrs-5 cells, and should be considered whenever results at the DNA
      level are correlated to results at the cell level. It is likely that similar
      responses will also be observed in other radiation-sensitive mutant cell lines
      deficient in dsb repair. There was no difference in the induction of dsb per Gy
      and dalton, as measured with AFIGE, between CHO and xrs-5 cells tested either in
      the exponential or in the plateau phase of growth.

PMID- 1347064
TI  - Chromosome damage induced by restriction endonucleases recognizing thymine-rich
      DNA sequences in electroporated CHO cells.
AB  - The influence of BrdU substitution of DNA in Chinese hamster cells on the
      frequencies of chromosomal aberrations induced by three restriction endonucleases
      which recognize thymine-rich sequences in DNA has been studied. The restriction
      enzymes chosen were Eco RI (recognition site G/AATTC), Sca I (AGT/ACT), and Dra I
      (TTT/AAA). A restriction enzyme that does not have thymine in the recognition
      sequence, Hae III (GG/CC), was also tried. These enzymes were introduced into
      cells by electroporation after two cell cycles of BrdU substitution and the
      aberration yields compared with that observed in non-substituted cells. Our
      results seem to indicate that the BrdU-substituted chromatin becomes resistant to
      the chromosome-breaking activity of the restriction enzymes recognizing thymine
      rich DNA sequences. These observations are compared with the patterns of cutting
      of isolated DNA as shown by agarose gel electrophoresis.

PMID- 1347065
TI  - A potential pitfall in the use of electroporation: cellular radiosensitization by
      pulsed high-voltage electric fields.
AB  - Chinese hamster ovary cells have been exposed to high-voltage electric fields
      causing electroporation (EP) and the interaction between EP and radiation-induced
      cell lethality investigated. There was a voltage-dependent decrease in plating
      efficiency, assessed immediately following EP, and cell viability, assessed at 24
      h. A linear decrease was seen for both. These decreases were accompanied by a
      voltage-dependent increase in cell volume, assessed immediately following EP. A
      good correlation between increases in cell volume and decreases in plating
      efficiency was seen (r = -0.91). The application of electric fields immediately
      prior to, or following, irradiation led to a radiosensitization of the cells.
      This radiosensitization still occurred when a 6 h interval was left between
      radiation and EP but was lost when cells were irradiated 24 h prior to EP. When
      cells were irradiated following EP, the radiosensitization was lost with a 1 h
      interval between the two treatments. These results suggest that, when studying
      the combined cellular effects of EP of macromolecules and radiation, care should
      be taken that sufficient time has elapsed between the two modalities to prevent
      the radiosensitization of cells.

PMID- 1347067
TI  - The relative biological effectiveness of 60Co gamma-rays, 55 kVp X-rays, 250 kVp
      X-rays, and 11 MeV electrons at low doses.
AB  - The relative biological effectiveness (RBE) of selected low-LET radiation
      modalities (55 kVp X-rays, 250 kVp X-rays, 60Co gamma-rays, and 11 MeV electrons)
      was investigated for survival of two cell lines (V79 and CHO). Detailed
      measurements were made in the low (0 to 3 Gy) dose range using an image cytometry
      device to accurately determine the number of cells assayed at each dose point.
      Data were also collected in the high dose range (0 to 10 Gy) using conventional
      counting and plating techniques. RBE values (+/- 1 SE) varied from 1.0 +/- 0.07
      (V79 cells) and 1.2 +/- 0.05 (CHO cells) at high doses to 1.3 +/- 0.07 (V79) and
      1.4 +/- 0.1 (CHO) at low doses for 55 kVp X-rays, from 1.1 +/- 0.05 (V79) and 1.1
      +/- 0.04 (CHO) at high doses to 1.1 +/- 0.06 (V79) and 1.2 +/- 0.2 (CHO) at low
      doses for 250 kVp X-rays, and from 1.1 +/- 0.08 (V79) and 1.0 +/- 0.04 (CHO) at
      high doses to 1.0 +/- 0.06 (V79) and 0.9 +/- 0.1 (CHO) at low doses for 11 MeV
      electrons. Only the low and high dose RBEs for 55 kVp X-rays relative to 60Co
      gamma-rays were significantly different.

PMID- 1347066
TI  - Chromosomal aberrations in human lymphocytes induced in vitro by very low doses
      of X-rays.
AB  - This paper presents results of a collaborative experiment between six
      laboratories which examined the yields of unstable chromosomal aberrations in
      human lymphocytes induced in vitro by X-rays over the dose range 0-300 mGy. The
      work included data points of nominal doses of 0, 3, 5, 6, 10, 20, 30, 50 and 300
      mGy. Cells from 24 donors were examined and a total of about 300,000 metaphases
      were scored. The work was undertaken to determine the limits of sensitivity of
      the system taking into account variations in scoring data due to inter-donor
      sample and inter-laboratory effects. Despite the existence of these effects,
      aberration yields significantly in excess of control values were seen at doses
      greater than 20 mGy and these were consistent with a linear extrapolation from
      higher doses. Below 20 mGy the observed dicentric yields were generally lower
      than background, but not significantly so. Excess acentric aberrations, on the
      other hand, and centric rings, were higher than the controls but the increase was
      usually not significant. It is concluded that the statistical uncertainties are
      such that below 20 mGy this technique cannot distinguish between a linear or a
      threshold model.

PMID- 1347069
TI  - Beta-radiation from tracer doses of 32P induces massive apoptosis in a Burkitt's
      lymphoma cell line.

PMID- 1347068
TI  - Effects of low-dose X-irradiation on mouse-brain aggregation cultures.
AB  - Biochemical and morphological differentiation in reaggregating mouse-brain cell
      cultures after low-dose radiation (0.5 Gy) in vitro was studied. Cells were
      irradiated on culture day 2, corresponding to embryonic day 15-16, and different
      glial and neuronal markers were followed through development to postnatal day 40.
      The shape and size of irradiated aggregates were more irregular and smaller
      compared with controls. Total amounts of DNA and protein were significantly lower
      in irradiated aggregates than in controls between days 8 and 20. After 30 days in
      culture activities of the glial markers glutamine synthetase (GS) and 2',3'
      cyclic nucleotide 3'-phosphodiesterase (CNP) were lower in X-irradiated
      aggregates than in controls. However, after 40 days the CNP activity in
      irradiated aggregates increased to levels above those of the controls. Irradiated
      and control aggregates did not differ significantly in neuronal marker enzyme
      activities, i.e. choline acetyltransferase (ChAT), acetylcholine esterase (AChE)
      and glutamic acid decarboxylase (GAD) measured on a per mg protein basis. On days
      20 and 30 the amount of nerve growth factor (NGF) was two-fold higher in
      irradiated aggregates compared with non-irradiated ones, suggesting that, after
      irradiation, surviving cells in culture were induced to produce more NGF. After
      40 days the amount of NGF in irradiated aggregates had decreased to the level
      found in the control aggregates.

PMID- 1347070
TI  - Increased radiation tolerance of mouse tongue epithelium after local
      conditioning.
AB  - The effect of local stimulation on mitotic activity and radiation tolerance was
      studied in mouse tongue mucosa. Silver nitrate solution (0.5-20%) was used for
      local conditioning. The most effective protocol comprised three daily treatments
      (days 0-2), yielding a delayed increase in 24 h mitotic counts by about 30% on
      days 5-7. The stimulating effect was independent of silver nitrate concentration.
      Sham treatment with saline or anaesthesia alone clearly depressed mitotic
      activity on days 2-4 without any subsequent overshoot. Radiation treatment was
      initiated on day 5 after three daily treatments with 3% silver nitrate solution.
      A top-up technique was employed, consisting of fractionated irradiation (300 kV X
      rays) of the whole snout, followed by graded local test doses (25 kV X-rays) to
      induce denudation in a confined area of the inferior tongue surface. Silver
      nitrate conditioning did not alter the radiosensitivity of the epithelium to
      single local doses, but shortened the latency to denudation from 11 to 8 days. In
      contrast, a clear increase in tolerance to fractionated irradiation, delivering 5
      x 2.5, 5 x 3.5, 5 x 4.5 Gy or 3 x 5.2 Gy in 7 days, was observed, equivalent to
      about four, two, one and two extra dose fractions. This approach may be a
      suitable way to increase radiation tolerance of oral mucosa in clinical
      radiotherapy.

PMID- 1347071
TI  - The influence of lumenal pH on the severity of acute radiation enteritis.
AB  - The severity of acute radiation injury to small bowel mucosa was studied as a
      function of lumenal pH at the time of irradiation. Rats were anaesthetized and 15
      cm of mid small bowel was exteriorized with the rest of the animal and intestine
      shielded in a lead box. The target intestine was segmented into three portions,
      each of which was filled with Tris buffer, adjusted to pH 5, 7 and 9
      respectively. Twenty minutes later the exteriorized bowel was given 1100 cGy X
      irradiation. Rats were sacrificed 4, 5 and 6 days later and the intestine
      histologically assessed for injury. The indices of injury were surviving crypt
      numbers, mucosal height and mucus-containing goblet cells. To verify that pH was
      the critical variable an identical study was done employing three buffers
      chemically different from Tris: MES (pH 5.5), ADA (pH 7), and CAPSO (pH 9). These
      animals were sacrificed 5 days postirradiation. For all three parameters, and on
      each day postirradiation, the pH 9 segment showed less damage than did the
      segments with lumenal pH 7 or 5. We conclude that lumenal pH at the time of
      irradiation plays a significant role in the severity of acute mucosal injury.
      Alkaline pH is relatively protective.

PMID- 1347073
TI  - Alpha-irradiation of haemopoietic tissue in pre- and postnatal mice: 2. Effects
      of mid-term contamination with 239Pu in utero.
AB  - The distribution of 239Pu in various tissues of foetal and postnatal offspring of
      pregnant mice, injected i.v. at 13 days gestation with 30 kBq 239Pu/kg (in some
      cases with 10 or 100 kBq/kg), together with the numbers of haemopoietic
      progenitors in the bone marrow, spleen and liver, were measured through to 1 year
      post-partum. The quality of the haemopoietic microenvironment in these mice was
      also measured using the renal-capsule implant method. The largest radiation dose
      received by any haemopoietic organ was that in the liver, amounting to 10-14 mGy,
      as reported previously. In spite of normal numbers of haemopoietic spleen colony
      forming cells (CFC-S) in the liver and seeding, at birth, into the bone marrow
      where the level of plutonium was minimal, a long-term deficit in their number
      rapidly developed. The development of the stromal microenvironment, however, was
      also deficient, suggesting that the dose of alpha-irradiation to the foetal liver
      was sufficient to cause sublethal damage in those cells destined to become the
      precursors of the supportive haemopoietic microenvironment in bone marrow and
      spleen. The results of this study suggest that although the placenta affords
      significant shielding to the tissues of the developing foetus from maternal
      contamination, the long-term effects on haemopoiesis are comparable to those in
      mice contaminated as adults. This further implies that the developing
      haemopoietic tissues are exquisitely sensitive to 239Pu contamination.

PMID- 1347072
TI  - Antimutagenic effects of radioprotector WR-2721 against fission-spectrum neurons
      and 60Co gamma-rays in mice.
AB  - The antimutagenic effects of the radiation protective agent, S-2-(3
      aminopropylamino)ethylphosphorothioic acid (WR-2721), were studied against
      fission-spectrum-neutron- and 60Co-gamma-ray-induced mutagenesis in mice.
      Mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus
      was measured 56 days following whole-body irradiation with JANUS neutrons (single
      doses, 50-150 cGy) or 60Co photons (single doses, 250-750 cGy). Splenic T
      lymphocytes from B6CF1 mice were grown in round-bottomed 96-microwell culture
      plates with or without the selective agent 6-thioguanine (6-TG). The mutant
      frequency, as a result of exposure to neutrons or 60Co photons, increased 100
      fold with dose. Doses of 150 cGy neutrons and 750 cGy 60Co photons were equally
      mutagenic. When animals were injected with WR-2721 at a dose of 400 mg/kg body
      weight, i.p., 30 min before whole-body irradiation with JANUS neutrons or 60Co
      photons, mutant frequencies were significantly reduced at all radiation doses
      (i.e. protection factors of 1.4 and 2.4, respectively). Thus, the aminothiols are
      effective antimutagens. A novel clinical application of these compounds could be
      in their use to protect against radiation- and/or chemotherapy-induced genotoxic
      damage to normal cells.

PMID- 1347074
TI  - Expression of oestrogen receptor and transforming growth factor-alpha in MCF-7
      cells after exposure to fractionated irradiation.
AB  - The expression of critical growth controlling genes was studied in MCF-7 cells
      after exposure to cumulative radiation doses of 20 and 60 Gy yielding cell lines
      called MCF-IR-1 and MCF-IR-3, respectively. The irradiated cell lines exhibited
      increased plating efficiencies but no differences in growth rates. MCF-IR-1/-IR-3
      cells showed a reduced oestrogen responsiveness as indicated by their diminished
      response to tamoxifen-induced growth arrest and 17 beta-oestradiol (E2)-induced
      growth stimulation. The reduced expression of oestrogen receptor (ER) was
      determined by quantitative immune peroxidase staining of single cells and by
      total cellular E2 binding. There was also a radiation dose-dependent increase in
      the radiosensitivity of MCF-IR-3 cells as determined by the radiobiological
      parameters alpha, beta, and D (mean inactivation dose). Using RNA protection
      assays the irradiated cell lines produced steady-state ER mRNA at reduced levels
      while the levels of TGF-alpha were unchanged in MCF-IR-1 cells but increased 2.8
      fold in MCF-IR-3 cells. A similar pattern was seen for TGF-alpha protein. While
      the current analyses cannot differentiate between radiation-induced altered gene
      expression or cell selection the results demonstrate that reduced ER expression
      and increased TGF-alpha expression are associated with the survival of MCF-7
      cells after fractionated irradiation in vitro. In contrast, the MCF-IR cells were
      found to be more radiosensitive in acute survival experiments.

PMID- 1347075
TI  - Steepness of the clinical dose-control curve and variation in the in vitro
      radiosensitivity of head and neck squamous cell carcinoma.
AB  - Inter-tumour heterogeneity in radiobiological parameters has been proposed as an
      explanation for the quite shallow dose-response curves for local tumour control
      after radiotherapy observed in clinical data. Variability in the intrinsic
      radiosensitivity is potentially a very strong source of variation in local
      control. A method is presented for forcing such variability into a direct
      analysis (maximum-likelihood estimation) of tumour control data. The method is
      used to reanalyse a series of local tumour control data in 181 patients with
      squamous cell carcinoma of the oropharynx taking the distribution of in vitro
      radiosensitivities from an independent series of patients into account. It is
      concluded that direct application of the in vitro radiosensitivities leads to an
      unrealistically high estimate for the number of target cells per cm3. A more
      realistic fit is obtained after including a dose-modifying factor to correct for
      the apparent difference between in vitro and clinical radiosensitivities. The
      value of this factor is estimated at 2.4 with approximate 95% confidence interval
      (CI) (1.3, 5.9). It is suggested that hypoxia plays a role in reducing the
      radiosensitivity of tumours in clinical radiotherapy. Using this method provides
      more biologically reasonable estimates of other radiobiological parameters. The
      target-cell doubling time during treatment is estimated at 3.2 days with 95% CI
      (1.7, 8.7) days. Estimates of the target cell density in typical patients vary
      between 1.8 x 10(-6) and 6.6 x 10(-4) when the delay before accelerated tumour
      growth is assumed to vary between 0 and 28 days. Using the method presented here,
      the shallow clinical dose-control curve is interpreted as a superposition of
      quite steep dose-response relationships in individual patients. The steepness of
      the dose-control curve for a typical patient is characterized by a normalized
      dose-response gradient (the percentage change in tumour control for a 1% change
      in total dose) of 7.3 after stratification for intrinsic radiosensitivity as
      compared with 1.6 if such stratification is not performed.

PMID- 1347076
TI  - Heat resistance and thermotolerance in a radiation-resistant cell line.
AB  - Exponentially growing TN-368 lepidopteran insect cells have a normal growth
      temperature of 28 degrees C. These cells were heated in water baths at various
      temperatures between 33 and 44 degrees C under conditions of constant or
      fractionated heating. Determinations of cell survival using colony formation as
      well as measurements of DNA and protein synthesis were performed to assess
      relative heat resistance and development of thermotolerance. The results
      demonstrate a marked heat resistance over previously reported findings from the
      same laboratory for dipteran Drosophila cells in culture. The degree of heat
      resistance is remarkable, especially when compared to the heat resistance of
      mammalian cells, i.e. TN-368 cell survival at 41.5 and 44 degrees C was somewhat
      similar to mammalian cell survival, even though these temperatures are 13.5 and
      16 degrees C above the normal growth temperature for TN-368 cells and 4.5 and 7
      degrees C above the growth temperature of mammalian cells. Furthermore, the
      lepidopteran cells maintain the ability to develop a notable amount of
      thermotolerance in addition to this heat resistance. Thermotolerance development
      alone is capable of enhancing survival by an additional 10,000-fold.
      Thermotolerance could also be detected at the level of protein synthesis as a
      more rapid recovery following heat treatment. In contrast, DNA synthesis
      inhibition was prolonged even further in cells receiving a prior heat treatment
      to induce thermotolerance. In summary, it appears that, in addition to their
      pronounced radiation resistance, the TN-368 cells are also quite resistant to
      heat. It remains to be seen whether a single mechanism could be responsible for
      resistance to these agents which act very differently.

PMID- 1347077
TI  - Changes in the paramagnetic centres in irradiated and heated dental enamel
      studied using electron paramagnetic resonance.
AB  - The EPR signals in dental enamel produced by radiation and by heat were studied.
      The inherent background signal at g = 2.005, and a radiation-produced signal at g
      = 2.002 have different saturation behaviour with microwave power, and this
      affords a method of signal optimization. Heating enamel at temperatures from 100
      degrees C to 450 degrees C produces a range of radical species from g = 2.002 to
      g = 2.005, which have been characterized by their g-values, line widths and
      saturation behaviour. Standard dental drilling produces a range of radicals which
      appear to be similar to those produced by heat.

PMID- 1347078
TI  - Latent equid herpesviruses 1 and 4: detection and distinction using the
      polymerase chain reaction and co-cultivation from lymphoid tissues.
AB  - The polymerase chain reaction (PCR) and co-cultivation were used to identify the
      lymphoreticular system as the site of latency of equid herpesvirus I (EHV-1).
      Primers for PCR were designed from aligned nucleotide sequences of the
      glycoprotein gB genes to amplify the same region of both the EHV-1 and EHV-4
      genomes. Subsequent restriction digests using specific enzymes distinguished the
      amplified fragments of the EHV-1 genome from those of the EHV-4 genome. Ten weeks
      following an experimental infection of five ponies with EHV-1, latent virus was
      detected by PCR and recovered by co-cultivation, predominantly from lymphoid
      tissues draining the respiratory tract. Significantly, latent EHV-1 also
      persisted in peripheral blood leukocytes (PBL). Latent EHV-4, presumably from a
      preceding natural infection, was also detected in some tissues, including PBL,
      from all animals. Of additional interest was the recovery of EHV-1 and -4 only in
      the presence of the ubiquitous EHV-2.

PMID- 1347080
TI  - Immunohistochemical demonstration of glutathione S-transferases in primary human
      breast carcinomas.
AB  - The expression of cytosolic glutathione S-transferase (GST) isoenzymes has been
      assessed in a series of 74 primary human breast carcinomas using an
      immunohistochemical method. GST pi was detected in sections from all 74 tumours;
      it was expressed by non-epithelial (stromal and inflammatory) cells in 62 tumours
      (84 per cent), but by tumour epithelium in only 35 (47 per cent). Non-neoplastic
      mammary epithelium was uniformly positive for GST pi. Expression of GST alpha and
      mu was observed in 19 and 42 per cent of the tumours, respectively, and was
      largely confined to the neoplastic component. Lack of staining of tumour
      epithelium for GST pi was significantly associated with poorer tumour
      differentiation (higher grade). There was no association between expression of
      any of the three isoenzymes and either menopausal status or expression of c-erbB
      2 oncogene protein product. Immunohistochemistry is a useful method for the
      investigation of expression and cellular localization of GSTs within tumours;
      such data are needed to improve our understanding of the role of these enzymes in
      neoplasia and in resistance to cytotoxic drug therapy.

PMID- 1347079
TI  - Thy-1 in hippocampus: normal anatomy and neuritic growth in Alzheimer's disease.
AB  - Abnormal neuritic sprouting is a prominent feature of Alzheimer's disease (AD),
      and the Thy-1 glycoprotein has a role in neurite growth in culture. We therefore
      investigated the distribution of Thy-1 immunoreactivity in the hippocampus of
      normal elderly patients and of AD patients. Normally, Thy-1 immunoreactivity,
      which was more prominent in CA1 than elsewhere in the hippocampus, was located
      mainly in irregular patches on the perikarya of pyramidal cells, their dendrites
      and axons. In AD, Thy-1-immunoreactive neurons were reduced in number in CA1, and
      there was diffuse staining of neurofibrillary tangle-bearing pyramidal cells, but
      neurofibrillary tangles themselves were not immunoreactive. There was also
      staining of disorganized arrays of dystrophic neurites, some with spiny processes
      and bizarre filopodial endings. Some Thy-1-immunoreactive dystrophic neurites
      entered senile plaques. The data confirm that there is extensive growth of
      abnormal neurites in AD and suggest that Thy-1 is involved in this process.

PMID- 1347081
TI  - A study of cell proliferation in formalin-fixed, wax-embedded bone marrow
      trephine biopsies using the monoclonal antibody PC10, reactive with proliferating
      cell nuclear antigen (PCNA).
AB  - We have investigated proliferation in bone marrow trephine biopsies from 32
      patients with normal or abnormal haemopoiesis, using the monoclonal antibody
      PC10, which detects proliferating cell nuclear antigen (PCNA), together with
      immunohistochemical markers of haemopoietic cell lineage. PCNA immunostaining
      revealed the pattern of proliferation within individual haemopoietic lineages in
      normal marrow. Two unexpected observations were made: of erythroid cells, only
      pro-erythroblasts and occasional early normoblasts reacted, and positivity of
      megakaryocytes was unrelated to nuclear lobulation or CD61 expression. The
      pathological cases represented conditions in which haemopoiesis is increased
      (reactive hyperplasia, chronic granulocytic leukaemia, myeloproliferative and
      myelodysplastic syndromes, megaloblastic anaemia). Increases in the number, and
      disturbances of the spatial organization, of PCNA-expressing cells were present
      to a variable extent in all cases. Sheets of PCNA-positive megaloblastoid
      erythrocytes were frequently found in myelodysplastic and myeloproliferative
      tissue, associated with marked disturbances in the spatial organization of all
      haemopoietic lineages. Cases of megaloblastic anaemia due to vitamin B12/folate
      deficiency also demonstrated greatly increased erythroid PCNA expression, with
      positivity in some giant metamyelocytes. In addition to reflecting increased
      proliferation, elevated PCNA expression in some bone marrow pathologies may be
      due to altered kinetics of the protein induced by disturbances in growth factor
      production.

PMID- 1347083
TI  - Alzheimer's disease and the environment.

PMID- 1347082
TI  - Familial neurofibromatosis type 1: clinical experience with DNA testing.
AB  - To determine how DNA testing for familial neurofibromatosis type 1 (NF-1) would
      be used in a clinical setting by patients and physicians, we performed
      confirmatory DNA testing on 24 individuals with a family history of NF-1 and on
      nine couples who requested DNA testing for current or future prenatal diagnosis.
      A further eight families were unsuitable for DNA linkage testing because of their
      pedigree structure. For the majority of persons the certainty of the test result
      was 95% to 99%. In five individuals, only one of whom was less than 6 years of
      age, the DNA-based diagnosis was discrepant with the clinical diagnosis at the
      time of referral. In all five cases, results of subsequent clinical re
      examinations were consistent with the DNA diagnosis. We conclude that DNA testing
      by linkage analysis may be most useful as an adjunct to the clinical diagnosis of
      familial NF-1 (1) in children less than 6 years of age in whom the full
      manifestations may not yet be apparent, (2) in NF-1 families interested in
      prenatal testing, and (3) when the resources available for a complete clinical
      examination are limited.

PMID- 1347084
TI  - Prostate carcinoma. Annual meeting, American Urological Association, Inc.,
      Washington, D.C., May 10-14, 1992.

PMID- 1347085
TI  - Alterations of the P53 gene are associated with the progression of a human
      prostate carcinoma.
AB  - P53 is a tumor suppressor gene that has been implicated in the molecular genetics
      of many human malignancies. Nucleotide alterations, most commonly single point
      mutations, have been shown not only to abrogate the p53 suppressor function but
      also to contribute to the transformed phenotype. We report the detection of a p53
      gene mutation in clinical specimens of a patient with relapsing prostate
      adenocarcinoma 14 years after definitive external beam radiation. The techniques
      of single strand conformation polymorphism analysis and direct sequencing of
      polymerase chain reaction generated products were used for this study. Analysis
      of tissue from different locations of the primary tumor revealed intratumoral
      molecular heterogeneity; the mutation was absent in 1 area but present in
      another. Tumor from a regional lymph node metastasis harbored the identical p53
      mutation. Furthermore, an additional genetic alteration, an allelic loss on
      chromosome 17p but not including the p53 gene, was observed only in the
      metastatic tissue. These observations in clinical specimens of primary and
      metastatic sites provide evidence for the association of the p53 gene in the
      progression of human prostate carcinoma.

PMID- 1347086
TI  - Lymphocyte subsets in healthy children during the first 5 years of life.
AB  - OBJECTIVE: To assess whether relative and absolute values of CD4 and CD8
      lymphocytes and CD4/CD8 ratio change in relation to age, and to estimate the
      fifth and 95th percentiles for these values in children of various ages. PATIENTS
      AND METHODS: Phenotypic analysis of lymphocyte subsets was performed on blood
      samples from 208 healthy children, aged 1 through 59 months, using standard flow
      cytometric techniques. RESULTS: Regression analysis demonstrated that CD4 and CD8
      lymphocyte counts declined significantly with advancing age (P less than .000001
      and P = .03, respectively). Since CD4 and CD8 counts depend on total lymphocyte
      count, the percentage of total lymphocytes of each phenotype was also analyzed
      and demonstrated that the CD4 percentage was highly age dependent (P less than
      .000001). The CD8 percentage increased with age (P = .0001) but not as much as
      the CD4 percentage decreased. Median CD4 counts (fifth and 95th percentiles) for
      children 2 through 3, 4 through 8, 12 through 23, and 24 through 59 months of age
      were 2.83 (1.46 to 5.11), 2.95 (1.69 to 4.61), 2.07 (1.02 to 3.60), and 1.80
      (0.90 to 2.86) x 10(9)/L, respectively. CONCLUSION: Healthy children's CD4
      lymphocyte counts are considerably higher than previously established adult
      values. These data demonstrate that age is an important consideration in
      interpretation of lymphocyte subsets in children. This may be especially relevant
      in children who are infected with the human immunodeficiency virus, where CD4
      lymphocyte values play a central role in monitoring disease progression and
      determining thresholds for medical interventions.

PMID- 1347087
TI  - The 1991 Albert Lasker Medical Awards. Clusters of master control genes regulate
      the development of higher organisms.

PMID- 1347088
TI  - Beta-blockade in older patients with myocardial infarction.

PMID- 1347089
TI  - Screening for von Hippel-Lindau disease by DNA polymorphism analysis.
AB  - OBJECTIVE: Von Hippel-Lindau (VHL) disease is a rare, inherited multisystem
      neoplastic disorder. There is no biochemical test available to distinguish VHL
      disease gene carriers from their healthy siblings. We evaluated DNA polymorphism
      analysis as a method for identifying disease gene carriers. DESIGN: Prospective
      comparison of the results of DNA analysis with a comprehensive clinical screening
      examination. SETTING: The Clinical Center of the National Institutes of Health.
      PATIENTS: Blood was collected from 182 members of 16 families with VHL disease.
      Forty-eight asymptomatic individuals, at risk of developing this hereditary
      illness (with an affected parent or sibling), were examined for occult disease at
      the Clinical Center of the National Institutes of Health and tested by DNA
      polymorphism analysis. RESULTS: DNA polymorphism analysis predicted nine disease
      gene carriers and 33 individuals with the wild-type (normal) allele among the 48
      individuals at risk of developing VHL disease; the test was not informative in
      six individuals. All nine individuals predicted to carry the VHL gene had
      evidence of occult disease on clinical examination. There was no clinical
      evidence of VHL disease in 32 of 33 individuals predicted to carry the wild-type
      allele. CONCLUSIONS: DNA polymorphism analysis can identify individuals likely to
      carry the VHL disease gene among asymptomatic members of disease families. This
      technique serves to focus attention on those individuals who require periodic
      medical examination and may help to alleviate the morbidity and mortality
      associated with this disease.

PMID- 1347090
TI  - Effects of long-term xamoterol in idiopathic dilated cardiomyopathy.
AB  - In prospective study, the beta 1-partial agonist xamoterol (200 mg daily) was
      given to 26 patients with idiopathic dilated cardiomyopathy (DCM) in addition to
      conventional therapy with digitalis, diuretics and vasodilators. The patients
      were followed for 35 +/- 15 months (6-53 months). Cardiothoracic ratio (CTR),
      left ventricular end-diastolic dimension (LVDD) and exercise heart rate
      decreased, and exercise duration, fractional shortening (FS) and ejection
      fraction (EF) increased after xamoterol therapy. Twenty-one patients survived and
      one patient dropped out at 7 months. Twelve of the 20 patients improved their
      NYHA functional class. Blood norepinephrine concentration (NE), LVDD, FS, EF and
      pulmonary capillary wedge pressure (PCWP) after xamoterol were significantly
      better in survivors than in non-survivors. Survival rate at 3 years was 83%. The
      results suggest that adjunctive xamoterol therapy in DCM has a beneficial effect
      on hemodynamics and symptoms. Prognosis will be satisfactory if improvement in
      parameters such as NE, LVDD, FS, EF and PCWP is seen during xamoterol therapy.

PMID- 1347091
TI  - Effects on coronary artery disease of lipid-lowering diet, or diet plus
      cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS)
AB  - To assess the effect of dietary reduction of plasma cholesterol concentrations on
      coronary atherosclerosis, we set up a randomised, controlled, end-point-blinded
      trial based on quantitative image analysis of coronary angiograms in patients
      with angina or past myocardial infarction. Another intervention group received
      diet and cholestyramine, to determine the effect of a greater reduction in
      circulating cholesterol concentrations. 90 men with coronary heart disease (CHD),
      who had a mean (SD) plasma cholesterol of 7.23 (0.77) mmol/l were randomised to
      receive usual care (U, controls), dietary intervention (D), or diet plus
      cholestyramine (DC), with angiography at baseline and at 39 (SD 3.5) months. Mean
      plasma cholesterol during the trial period was 6.93 (U), 6.17 (D), and 5.56 (DC)
      mmol/l. The proportion of patients who showed overall progression of coronary
      narrowing was significantly reduced by both interventions (U 46%, D 15%, DC 12%),
      whereas the proportion who showed an increase in luminal diameter rose
      significantly (U 4%, D 38%, DC 33%). The mean absolute width of the coronary
      segments (MAWS) studied decreased by 0.201 mm in controls, increased by 0.003 mm
      in group D, and increased by 0.103 mm in group DC (p less than 0.05), with
      improvement also seen in the minimum width of segments, percentage diameter
      stenosis, and edge-irregularity index in intervention groups. The change in MAWS
      was independently and significantly correlated with LDL cholesterol concentration
      and LDL/HDL cholesterol ratio during the trial period. Both interventions
      significantly reduced the frequency of total cardiovascular events. Dietary
      change alone retarded overall progression and increased overall regression of
      coronary artery disease, and diet plus cholestyramine was additionally associated
      with a net increase in coronary lumen diameter. These findings support the use of
      a lipid-lowering diet, and if necessary of appropriate drug treatment, in men
      with CHD who have even mildly raised serum cholesterol concentrations.

PMID- 1347092
TI  - Mechanism of grass-pollen-induced asthma.
AB  - Many asthmatics are sensitive to rye-grass pollen, but pollen grains are too
      large to penetrate the lower airways. Our aim was to investigate the mechanism by
      which rye-grass pollen causes asthma. A major allergen of rye-grass pollen, Lol
      pIX, is located in intracellular starch granules within pollen grains. In-vitro
      tests showed that pollen grains are ruptured in rainwater by osmotic shock, each
      grain releasing about 700 starch granules into the environment. These granules
      are small enough to enter the airways (less than 3 microns in diameter). The
      starch granules were present in atmospheric samples taken during the pollen
      season, and showed a 50-fold increase in atmospheric concentration on days
      following rainfall. Isolated granules elicited IgE-mediated responses in
      asthmatic patients, and 4 patients with rainfall-associated asthma who underwent
      an inhalation challenge test had striking bronchial constriction after exposure
      to starch granules. Starch granules released from rye-grass pollen seem to be
      capable of causing asthma.

PMID- 1347093
TI  - Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic
      renal failure.
AB  - Nitric oxide (NO), synthesised from L-arginine, contributes to the regulation of
      blood pressure and to host defence. We describe in-vitro and in-vivo evidence
      that NO synthesis can be inhibited by an endogenous compound, NG,NG
      dimethylarginine (asymmetrical dimethylarginine, ADMA). In man, this inhibitor is
      found in plasma and more than 10 mg is excreted in urine over 24 h. However, in
      patients with end-stage chronic renal failure, who have little or no urine
      output, elimination is blocked and circulating concentrations of the inhibitor
      rise sufficiently to inhibit NO synthesis. Accumulation of endogenous ADMA,
      leading to impaired NO synthesis, might contribute to the hypertension and immune
      dysfunction associated with chronic renal failure.

PMID- 1347095
TI  - Liver regeneration in recipients and donors after transplantation.
AB  - Reduced-size liver grafts from related donors may not be of an optimal size for
      adequate function in the recipient. Therefore, liver-graft regeneration is
      clinically important. We evaluated liver regeneration by liver-volume
      determinations with serial computed tomography scans in four recipients (aged 9
      months to 12 years) and their donors (all fathers of the recipients) after living
      related liver transplantation. Standard liver volume was calculated from the
      recipient's body-surface area. In each recipient, the size of the transplanted
      liver tended to converge to the standard liver volume with time, regardless of
      whether initial liver-graft volume was smaller or larger than standard liver
      volume. In addition, transplanted liver in the recipient regenerated much faster
      than remnant liver in the donor, even though both consisted of the same
      hepatocytes, which suggests that regeneration is regulated mainly by factors
      other than the hepatocytes themselves.

PMID- 1347094
TI  - Mutations of p53 and ras genes in radon-associated lung cancer from uranium
      miners.
AB  - Radon increases the risk of lung cancer in smoking and non-smoking underground
      miners. To investigate the mutational spectrum associated with exposure to high
      levels of radon, we sequenced exons 5-9 of the p53 tumour suppressor gene and
      codons 12-13 of the Ki-ras protooncogene in 19 lung cancers from uranium miners
      exposed to radon and tobacco smoke. Mutations were not found in Ki-ras, but 9 p53
      mutations, including 2 deletions, were found in 7 patients by direct DNA
      sequencing after polymerase chain reaction amplification of DNA from formalin
      fixed, paraffin-embedded tissue. In tumours from 5 patients, the mutation
      produced an aminoacid change and an increased nuclear content of p53 protein. The
      tumours with either a stop codon or frame-shift deletion in the p53 gene were
      negative by immunohistochemistry. None of the mutations were G:C to T:A
      transversions in the coding strand of the p53 gene, which are the most frequent
      base substitutions associated with tobacco smoking, and none were found at the
      hotspot codons described in lung cancer. The observed differences from the usual
      lung cancer mutational spectrum may reflect the genotoxic effects of radon.

PMID- 1347096
TI  - Location of gene for Gorlin syndrome.
AB  - The Gorlin (naevoid-basal-cell-carcinoma) syndrome is an autosomal dominant
      disorder characterised by multiple naevoid basal-cell carcinomas, recurrent
      odontogenic keratocysts, skeletal anomalies, intracranial calcification, and
      developmental malformations. Characterisation of the gene that causes the
      syndrome may improve our understanding of the pathogenesis of other basal-cell
      carcinomas. By linkage analysis, we have shown that the gene is located on
      chromosome 9q22.3-q31; the most likely position is between DNA markers D9S12 and
      D9S53. Location of the gene for Gorlin syndrome offers the possibility that DNA
      markers can be used in risk estimation and presymptomatic identification of
      patients for surveillance.

PMID- 1347097
TI  - The oesophagus and chest pain of uncertain cause.

PMID- 1347098
TI  - Pop goes the asthma.

PMID- 1347099
TI  - Towards a malarial vaccine.

PMID- 1347100
TI  - Measurement imprecision: ignore or investigate?

PMID- 1347101
TI  - Cardiogenic embolism to the brain.

PMID- 1347102
TI  - Incidence of development of factor VIII and factor IX inhibitors in
      haemophiliacs.
AB  - The development of factor VIII:C inhibitors remains one of the most serious
      complications of repeated transfusion in patients with haemophilia A. The
      proportion of patients affected has been reported to range from 3.6% to 25%, but
      these figures have been derived mainly from retrospective data and from total
      numbers of known haemophiliacs instead of number at true risk. The assessment
      here is based on a prospective study, started in 1976, on the incidence of
      inhibitor development in haemophiliacs born after 1970 whose FVIII or FIX
      activity was 5% or less, and who had received replacement therapy at least once.
      46 of 63 children with haemophilia A and 13 of 17 with haemophilia B fulfilled
      the enrollment criteria. Inhibitors developed only in haemophilia A patients who
      had previously been treated with FVIII products--inhibitor concentrations were
      high in 12 and low in 3. Inhibitors developed in 24% (15/63) of all haemophilia A
      patients, and in 52% (14/27) of those with severe disease. The incidence of
      inhibitor development for all haemophilia patients was 39.1 per 1000 patient
      years of observation. All inhibitors were first detected when patients were aged
      0.08-5.2 years. The cumulative risk was 33% at age 6 years. The findings indicate
      that previous reports have underestimated the risk of acquiring FVIII inhibitors.
      Prospective, standardised studies, especially in children, are needed for the
      assessment of the true risk of this complication.

PMID- 1347103
TI  - Hypocholesterolaemic effects of lovastatin in familial defective apolipoprotein B
      100.
AB  - Familial defective apolipoprotein B-100 (FDB) is an autosomal dominant disorder
      associated with hypercholesterolaemia in which an aminoacid substitution in
      apoprotein B-100 leads to low-density lipoprotein (LDL) particles which have
      defective binding to the LDL receptor. All known patients are heterozygous, and
      their plasma contains normal and poorly binding LDL particles. 12
      hypercholesterolaemic patients from 10 unrelated families with FDB were treated
      with lovastatin. In 6 patients treated with 20 mg lovastatin daily, LDL
      cholesterol decreased by 21.5% from 6.23 to 4.89 mmol/l (95% confidence interval
      0.74, 1.96 mmol/l), whereas it fell by 32.1%, from 6.99 to 4.81 mmol/l (95% CI
      1.55, 2.70 mmol/l), in 9 patients who received 40 mg daily. These results
      indicate that the hypercholesterolaemia of FDB may respond to treatment with
      statins.

PMID- 1347104
TI  - Simian retroviruses, poliovaccine, and origin of AIDS.

PMID- 1347105
TI  - Abortion in Ireland.

PMID- 1347106
TI  - Breastfeeding and intelligence.

PMID- 1347107
TI  - Breastfeeding and intelligence.

PMID- 1347108
TI  - Breastfeeding and intelligence.

PMID- 1347109
TI  - Breastfeeding and intelligence.

PMID- 1347110
TI  - Breastfeeding and intelligence.

PMID- 1347111
TI  - Breastfeeding and intelligence.

PMID- 1347112
TI  - Is ondansetron "too expensive"?

PMID- 1347113
TI  - Fetal oxygen saturation measurement by transmission pulse oximetry.

PMID- 1347114
TI  - Contraception, papillomavirus, and cervical cancer.

PMID- 1347115
TI  - Carbocisteine polymorphism and disease.

PMID- 1347116
TI  - Localisation of gene for the naevoid basal-cell carcinoma syndrome.

PMID- 1347117
TI  - Aspergillus in pepper.

PMID- 1347118
TI  - Fractals and retinal vessels.

PMID- 1347119
TI  - Fractal electroencephalography.

PMID- 1347120
TI  - Helicobacter pylori infection and overcrowding in childhood.

PMID- 1347121
TI  - Allergy to ergot-derived dopamine agonists.

PMID- 1347122
TI  - Possible penicillin allergy after eating chicken.

PMID- 1347123
TI  - Donor-recipient bone-marrow matching by single strand conformation polymorphism
      analysis.

PMID- 1347124
TI  - HIV seroprevalence and antenatal clinics.

PMID- 1347125
TI  - HIV seroprevalence and antenatal clinics.

PMID- 1347126
TI  - HIV seroprevalence and antenatal clinics.

PMID- 1347127
TI  - HIV seroprevalence and antenatal clinics.

PMID- 1347128
TI  - HIV seroprevalence and antenatal clinics.

PMID- 1347129
TI  - Bilateral cataract surgery.

PMID- 1347131
TI  - Meta-analysis confounded.

PMID- 1347130
TI  - Healthy volunteers and alcohol abuse.

PMID- 1347132
TI  - Abuse of brand names in era of essential drugs.

PMID- 1347133
TI  - Isolation of Latin American epidemic strain of Vibrio cholerae O1 from US Gulf
      Coast.

PMID- 1347134
TI  - Toxigenic Vibrio cholerae O1 and cargo ships entering Gulf of Mexico.

PMID- 1347135
TI  - Mupirocin-resistant Staphylococcus aureus.

PMID- 1347136
TI  - Platelet size and outcome after myocardial infarction.

PMID- 1347137
TI  - HIV-1 sensitivity to zidovudine and clinical outcome.

PMID- 1347138
TI  - Zidovudine.

PMID- 1347139
TI  - HIV-1 sensitivity to zidovudine and clinical outcome.

PMID- 1347140
TI  - Allergy, oral sex, and HIV.

PMID- 1347141
TI  - Finnish trial of cardiovascular disease prevention.

PMID- 1347142
TI  - HIV-exposed twins.

PMID- 1347143
TI  - Regulation of glucose kinetics in trauma patients by insulin and glucagon.
AB  - The current study was undertaken to evaluate the contribution of insulin and
      glucagon to regulation of glucose metabolism in man following severe, traumatic
      injury by manipulating concentrations of insulin and glucagon with infusions of
      somatostatin. Glucose kinetics were assessed with [U-14C, 6-(3)H]glucose in
      severely injured patients and compared with data obtained from patients
      recovering from minor, elective operative procedures. Glucose production was
      significantly increased in subjects with traumatic injury compared with control
      subjects (13.0 +/- 0.63 mumol/kg/min v 8.6 +/- 0.27 mumol/kg/min). There was no
      impairment in glucose oxidation by the injured patients. Modulation of insulin
      and glucagon with somatostatin indicated that non-insulin-mediated glucose uptake
      (NIMGU) was significantly elevated in injured patients (12.2 +/- 0.94
      mumol/kg/min v 7.4 +/- 0.61 mumol/kg/min). Hepatic glucose output (HGO) in the
      absence of glucagon was also significantly elevated in injured patients (12.2 +/-
      1.20 mumol/kg/min v 5.8 +/- 1.08 mumol/kg/min). Indirect calorimetry showed a 27%
      increase in resting energy expenditure (REE). Increased protein oxidation
      accounted for 56% of the increase in REE. Changes in carbohydrate and lipid
      oxidation accounted for 28% and 15% of the increase in REE. There was no
      correlation between the injury severity score of the injured patient and the
      degree of metabolic abnormality. It is concluded from these studies that (1)
      injured patients have a high rate of glucose turnover in the absence of glucagon
      and insulin; (2) the reliance on glucose as a source of energy is not diminished
      in injured subjects; and (3) increases in protein oxidation account for the
      majority of the increased REE found in injured patients.

PMID- 1347144
TI  - Characterization and genetic mapping of a short, highly repeated, interspersed
      DNA sequence from rice (Oryza sativa L.).
AB  - A short, highly repeated, interspersed DNA sequence from rice was characterized
      using a combination of techniques and genetically mapped to rice chromosomes by
      restriction fragment length polymorphism (RFLP) analysis. A consensus sequence
      (GGC)n, where n varies from 13-16, for the repeated sequence family was deduced
      from sequence analysis. Southern blot analysis, restriction mapping of repeat
      element-containing genomic clones, and DNA sequence analysis indicated that the
      repeated sequence is interspersed in the rice genome, and is heterogeneous and
      divergent. About 200,000 copies are present in the rice genome. Single copy
      sequences flanking the repeat element were used as RFLP markers to map individual
      repeat elements. Eleven such repeat elements were mapped to seven different
      chromosomes. The strategy for characterization of highly dispersed repeated DNA
      and its uses in genetic mapping, DNA fingerprinting, and evolutionary studies are
      discussed.

PMID- 1347146
TI  - Stimulation of N-methyl-D-aspartate receptor-mediated calcium entry into
      dissociated neurons by reduced and oxidized glutathione.
AB  - The effects of GSH (gamma-glutamylcysteinylglycine) and GSSG on intracellular
      calcium levels ([Ca2+]i) were investigated using fura-2-loaded dissociated brain
      cells from newborn rat pups. Both produced concentration-dependent increases in
      [Ca2+]i (EC50 values of 914.3 +/- 190.5 and 583.0 +/- 97.2 microM for GSH and
      GSSG, respectively), similar to that observed with N-methyl-D-aspartate (NMDA)
      and other agonists at the NMDA receptor. Maximum response (expressed as
      percentage change in [Ca2+]i relative to basal) was significantly greater for
      GSSG (37.5 +/- 1.6%) than for GSH (25.3 +/- 1.6%). The response to both agents
      was prevented or reversed by competitive (100 microM) (-)-2-amino-5-
      phosphonovalerate and noncompetitive (400 nM) MK-801 or 1.0 mM Mg2+ antagonists
      of NMDA receptor-mediated calcium entry, even at concentrations of GSH and GSSG
      normally producing maximal response. The idea that these effects are mediated, at
      least in part, by interaction with the NMDA receptor was supported by the effects
      of GSH and GSSG on the binding of the NMDA receptor ligand [3H]CGP-39653 to
      membranes isolated from hippocampal and cortical homogenates. Both GSH and GSSG
      displaced bound [3H]CGP-39653, with IC50 values of 0.93 +/- 0.18 and 11.02 +/-
      1.22 microM, respectively, and produced an increase in the apparent Kd of binding
      (control, 8.92 +/- 0.83 nM, and GSH, 13.31 +/- 1.19 nM; control, 11.59 +/- 0.35
      nM, and GSSG, 18.73 +/- 0.66 nM). However, both also produced modest reductions
      in Bmax (control, 1265 +/- 69 fmol/mg of protein, and GSH, 901 +/- 73 fmol/mg of
      protein; control, 1068 +/- 30 fmol/mg of protein, and GSSG, 730 +/- 18 fmol/mg of
      protein) and Hill slopes (GSH, 0.66 +/- 0.02; GSSG, 0.62 +/- 0.04). This suggests
      complex kinetics for the interaction of GSH and GSSG with the NMDA receptor.
      Taken together, the results suggest the potential for modulation of the NMDA
      receptor complex by GSH and GSSG.

PMID- 1347145
TI  - Sequence of a cDNA encoding nitrite reductase from the tree Betula pendula and
      identification of conserved protein regions.
AB  - The sequence of an mRNA encoding nitrite reductase (NiR, EC 1.7.7.1.) from the
      tree Betula pendula was determined. A cDNA library constructed from leaf poly(A)+
      mRNA was screened with an oligonucleotide probe deduced from NiR sequences from
      spinach and maize. A 2.5 kb cDNA was isolated that hybridized to an mRNA, the
      steady-state level of which increased markedly upon induction with nitrate. The
      nucleotide sequence of the cDNA contains a reading frame encoding a protein of
      583 amino acids that reveals 79% identity with NiR from spinach. The transit
      peptide of the NiR precursor from birch was determined to be 22 amino acids in
      size by sequence comparison with NiR from spinach and maize and is the shortest
      transit peptide reported so far. A graphical evaluation of identities found in
      the NiR sequence alignment revealed nine well conserved sections each exceeding
      ten amino acids in size. Sequence comparisons with related redox proteins
      identified essential residues involved in cofactor binding. A putative binding
      site for ferredoxin was found in the N-terminal half of the protein.

PMID- 1347147
TI  - Isoproterenol-initiated beta-adrenergic receptor diacytosis in cultured cells.
AB  - The kinetics of the return of internalized beta-adrenergic receptors to the
      plasma membrane were measured in human astrocytoma cells. The movement of
      [125I]iodopindolol-labeled receptors back to the plasma membrane was measured
      directly and was shown to occur with a t1+2 of 3-4 min. Unlabeled receptors
      appeared to exhibit the same kinetics of externalization. The process was not
      inhibited by low concentrations (1-10 microM) of propranolol or even high
      concentrations of isoproterenol (0.1-1.0 mM). Higher concentrations of
      propranolol (0.1-1.0 mM) and other lipophilic amines inhibited externalization.
      The results are consistent with the proposal that catecholamine-induced beta
      adrenergic receptor internalization and externalization (diacytosis) occur via
      the clathrin-coated pit/endosome pathway.

PMID- 1347148
TI  - Waardenburg's syndrome patients have mutations in the human homologue of the Pax
      3 paired box gene.
AB  - Waardenburg's syndrome (WS) is an autosomal dominant combination of deafness and
      pigmentary disturbances, probably caused by defective function of the embryonic
      neural crest. We have mapped one gene for WS to the distal part of chromosome 2.
      On the basis of their homologous chromosomal location, their close linkage to an
      alkaline phosphatase gene, and their related phenotype, we suggested that WS and
      the mouse mutant Splotch might be homologous. Splotch is caused by mutation in
      the mouse Pax-3 gene. This gene is one of a family of eight Pax genes known in
      mice which are involved in regulating embryonic development; each contains a
      highly conserved transcription control sequence, the paired box. Here we show
      that some families with WS have mutations in the human homologue of Pax-3.
      Mutations in a related gene, Pax-6, which, like Pax-3, has both a paired box and
      a paired-type homeobox sequence, cause the Small-eye mutation in mice and
      aniridia in man. Thus mutations in the Pax genes are important causes of human
      developmental defects.

PMID- 1347149
TI  - An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome.
AB  - Here we report the identification and characterization of a gene defect causing
      Waardenburg's syndrome with hearing loss in a large Brazilian family. This
      demonstrates a mutation causing Waardenburg's syndrome as well as a mutation
      causing a form of congenital deafness. The mutation was found in the HuP2 gene, a
      member of the paired domain family of proteins that bind DNA and regulate gene
      expression. The mutation occurred in 100% of the cases with the disease in this
      family and was absent in a random sample of 50 unrelated control subjects.
      Identification of the Waardenburg's syndrome gene and future characterization of
      its gene product is likely to increase our understanding of the pathogenesis of
      this disorder and may allow prevention of deafness of this type.

PMID- 1347150
TI  - C. elegans unc-4 gene encodes a homeodomain protein that determines the pattern
      of synaptic input to specific motor neurons.
AB  - The creation of neural circuits depends on the formation of synapses between
      specific sets of neurons. Little is known, however, of the molecular mechanisms
      governing synaptic choice. A mutation in the unc-4 gene alters the pattern of
      synaptic input to one class of motor neurons in the Caenorhabditis elegans
      ventral nerve cord. In unc-4(e120), the presynaptic partners of VA motor neurons
      are replaced with interneurons appropriate to motor neurons of the VB class. This
      change in neural specificity is not accompanied by any detectable effects on
      neuronal morphology or process extension. We show that the absence of a
      functional unc-4 gene product accounts for the mutant phenotype. The unc-4 gene
      encodes a homeodomain protein and thus is likely to function as a transcription
      factor. The limited effect of the unc-4 null mutation on cell fate may mean that
      unc-4 regulates the expression of a small number of target genes and that the
      products of these genes are directly involved in the choice of synaptic partners.

PMID- 1347151
TI  - Linkage of regression and malignant conversion of rabbit viral papillomas to MHC
      class II genes.
AB  - Human papillomaviruses associated with cutaneous and anogenital cancers induce
      intraepithelial precursor lesions which may regress spontaneously or progress
      into invasive carcinomas. Cell-mediated immune responses are probably involved in
      regression of precancerous lesions and the polymorphism of the genes responsible
      may thus have a key role in the variability of the host response. Skin warts and
      cancers induced in rabbits by Shope papillomavirus provide a model to test this
      hypothesis. We analysed a restriction-fragment-length polymorphism of major
      histocompatibility complex class I and class II genes and T-cell receptor beta
      chain genes in infected domestic rabbits. We found a strong linkage between wart
      regression and a DR alpha EcoRI fragment, and an increased relative risk of
      malignant transformation associated with a DQ alpha PvuII fragment. This
      indicates a genetic control of wart evolution, involving genes in the class II
      region of the major histocompatibility complex.

PMID- 1347152
TI  - Activation of dopamine D1 receptors does not affect D2 receptor-mediated
      inhibition of acetylcholine release in rabbit striatum.
AB  - The possible involvement of dopamine D1 receptors in the regulation of
      acetylcholine release in the rabbit caudate nucleus was investigated. Caudate
      slices, preincubated with [3H]choline, were superfused continuously and subjected
      to electrical field stimulation with only a single pulse. In agreement with the
      view that the release of acetylcholine evoked by a single electrical pulse is not
      influenced by endogenous transmitters, atropine and domperidone failed to
      increase the evoked release of [3H]acetylcholine, whereas oxotremorine and
      quinpirole caused a concentration-dependent inhibition of transmitter release.
      Neither the dopamine D1 receptor antagonist SCH 23390 nor the D1 agonist SKF
      38393 in a concentration range of 0.01-1 mumol/l changed the evoked
      [3H]acetylcholine release. The inhibitory effect of the dopamine D2 receptor
      agonist quinpirole was virtually abolished in the presence of 0.1 mumol/l
      domperidone and diminished in the presence of 1 mumol/l SCH 23390. It remained
      unchanged in the presence of 1 mumol/l SKF 38393. It is concluded that the
      inhibition of acetylcholine release by dopamine is mediated exclusively via
      presynaptic dopamine D2 receptors and that the antagonistic effect of SCH 23390
      on the inhibition of acetylcholine release by quinpirole is due to its
      interaction with dopamine D2 rather than D1 receptors located on cholinergic
      nerve terminals.

PMID- 1347153
TI  - Activation of beta 2-adrenoceptors by isoprenaline and adrenaline enhances
      noradrenaline release in cortical kidney slices of young spontaneously
      hypertensive rats.
AB  - The aim of the present study was to investigate beta-adrenoceptor modulation of
      noradrenaline release from sympathetic nerves in superfused cortical kidney
      slices of 4-week-old spontaneously hypertensive rats (SHR) and age-matched
      controls (WKY). After preincubation with 3H-noradrenaline the kidney slices were
      electrically stimulated in superfusion chambers. The stimulation induced (S-I)
      outflow of radioactivity was mainly composed of unmetabolized 3H-noradrenaline in
      both strains and thus taken as an index of noradrenaline release. There was a
      frequency-dependent (1.25-20 Hz) increase in the S-I outflow of radioactivity. At
      all stimulation frequencies tested S-I outflow of radioactivity was similar or
      even slightly lower in SHR than in WKY kidney slices in either the absence or
      presence of cocaine (10 mumol/l). The non-selective beta-adrenoceptor agonists
      isoprenaline (0.1 mumol/l) and adrenaline (0.01 and 0.1 mumol/l) enhanced S-I
      outflow of radioactivity. The facilitatory effects of isoprenaline (0.1 mumol/l)
      and adrenaline (0.1 mumol/l) were blocked by the selective beta 2-adrenoceptor
      antagonist ICI 118551 (0.1 mumol/l) but not by the selective beta 1-adrenoceptor
      antagonist atenolol (0.3 mumol/l). The cell-permeable cAMP analogue 8-bromo-cAMP
      (300 mumol/l) enhanced S-I outflow of radioactivity to a similar extent in both
      SHR and WKY kidney slices. A combination of 8-bromo-cAMP (300 mumol/l) and
      adrenaline (0.1 mumol/l) did not enhance S-I outflow of radioactivity to a
      greater extent than 8-bromo cAMP (300 mumol/l) alone in both strains.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1347154
TI  - Presynaptic effects of dopexamine hydrochloride in the canine kidney.
AB  - The effects of dopexamine on the vasoconstrictor response to renal nerve
      stimulation and noradrenaline were determined in anesthetized dogs. Renal
      vasoconstriction was repeated during the sequential administration of iso-osmotic
      saline, dopexamine, dopexamine plus the DA1-dopamine receptor antagonist, SCH
      23390, and dopexamine plus SCH 23390 and the DA2-dopamine receptor antagonist,
      domperidone. Renal nerve stimulation-induced vasoconstriction did not change with
      dopexamine or dopexamine plus SCH 23390, but increased with the addition of
      domperidone. Dopexamine also potentiated noradrenaline-induced vasoconstriction.
      Antagonists alone had no affect on the vasoconstrictor response to either
      stimulus. The findings suggest that the absence of an effect of dopexamine on
      neuronally-induced renal vasoconstriction was a consequence of a balance between
      its actions at presynaptic DA2-dopamine receptors (attenuated vasoconstriction)
      and its ability to inhibit the uptake1 transporter (enhanced vasoconstriction).

PMID- 1347155
TI  - Prejunctional opioid mu-receptors and adenosine A1-receptors on the sympathetic
      nerve endings of the rat tail artery interact with the alpha 2-adrenoceptors.
AB  - Experiments were designed to study the interaction between prejunctional alpha 2
      adrenoceptors and both adenosine and opioid receptors at the postganglionic
      sympathetic nerve endings innervating the tail artery of the rat. Segments of
      this vessel were preincubated with [3H]-noradrenaline and then
      perfused/superfused with [3H]-noradrenaline-free medium. Their perivascular
      nerves were field stimulated with standard stimulation parameters: 24 pulses at
      0.4 Hz, 0.3 ms, 200 mA. In some experiments, the stimulation parameters were
      adjusted in order to obtain similar reference release values despite the presence
      of a first release-modulating drug. The adenosine agonist 5'-N
      ethylcarboxamidoadenosine (NECA; 0.3-10 mumol/l) and [D
      Ala2,MePhe4,Glyol5]enkephalin (DAGO; 0.3-10 mumol/l) depressed the stimulation
      evoked overflow of tritium in a concentration dependent manner. The release
      inhibiting effect of both NECA and DAGO was enhanced in the presence of the alpha
      2-adrenoceptor antagonist rauwolscine (3 mumol/1) while it was attenuated in the
      presence of the alpha 2-adrenoceptor agonist 5-bromo-6-[2-imidazolin-2yl-amino]
      quinoxaline (UK-14,304; 0.1 mumol/l). These changes occurred both at standard and
      adjusted stimulation parameters. These results demonstrate that the prejunctional
      adenosine A1- and opioid mu-receptors interact with the prejunctional alpha 2
      adrenoceptors. The level at which these interactions take place (receptors
      themselves or transduction mechanisms) as well as the physiological significance
      of the phenomenon remain to be determined.

PMID- 1347157
TI  - [Parkinsonism following addition of fluoxetine to the treatment with neuroleptics
      or carbamazepine].
AB  - This article describes three patients who developed parkinsonism when fluoxetine
      was added to their existing medication (neuroleptics or carbamazepine). Based on
      published pharmacological and neuroanatomical research we postulate a serotonin
      dopamine antagonism to be operative in the development of drug-induced
      parkinsonism. Alternatively, the possibility of a pharmacokinetic interaction
      remains.

PMID- 1347158
TI  - [Subjective side effects of neuroleptics].

PMID- 1347156
TI  - Comparison of a cloned ANF-sensitive guanylate cyclase (GC-A) with particulate
      guanylate cyclase from adrenal cortex.
AB  - Recently, an ANF-sensitive guanylate cyclase (GC-A) has been cloned from a rat
      brain cDNA library. Here we studied the stimulation of cyclic GMP accumulation in
      response to atrial natriuretic factor (ANF), urodilatin and atriopeptin I (AP-1)
      in a rat glioma C6 cell line permanently transfected with GC-A as well as GC-A
      activity in membranes from these C6 cells and in membranes from COS-7 cells that
      were transiently transfected with GC-A. We also measured binding affinities for
      these natriuretic peptides in the membrane preparations. These characteristics of
      GC-A were compared to those of membrane preparations from adrenal cortex of
      bovine and human origin. The order of potency of stimulation of cyclic GMP
      accumulation in permanently transfected glioma cells was ANF greater than
      urodilatin greater than AP I; AP I stimulated cyclic GMP accumulation. A similar
      order of potency was obtained for stimulation of guanylate cyclase activity in
      membranes from permanently transfected glioma cells as well as from transiently
      transfected COS-7 cells. In contrast, AP-1 was uneffective to stimulate guanylate
      cyclase in membrane preparations from adrenal cortex from bovine as well as from
      human origin. Furthermore, urodilatin was equipotent to ANF in these
      preparations. Binding affinities were comparable for ANF and urodilatin in
      membranes from cells transfected with GC-A and in membranes from adrenal cortex
      of both sources, whereas AP-1 had a weaker affinity in all preparations
      studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347159
TI  - Frederick E. Samson Symposium on Neurochemistry: Toxic and Trophic Effects of
      Neuronal Stimulation, Missouri, October 26-27, 1990.

PMID- 1347160
TI  - Isolation and characterization of endogenous modulators for GABA system.
AB  - Pig brain extracts from both soluble and membrane fractions were found to contain
      potent inhibitors for GABA synthesizing enzyme, GAD, referred to as endogenous
      GAD inhibitors (EGIs) and for the binding of GABA agonist, muscimol, referred to
      as muscimol binding inhibitors (MBIs). EGIs and MBIs were first purified through
      gel-filtration Bio-Gel P-2 columns, in which multiple activity peaks were
      observed. One of them appears to be co-eluted with either L-glutamate or GABA.
      However, others are clearly separated from L-glutamate or GABA. EGIs were found
      to be low MW (less than 1,800 dalton), heat and acid-base stable, negatively
      charged, non hydrophobic substances. MBIs were found to be low MW (less than
      1,800 dalton) neutral or positively charged substances. MBIs had no effect on
      [3H]flunitrazepam (FNZP) binding, indicating that they are not endogenous
      benzodiazepine receptor ligands and they may act specifically on GABA binding
      site.

PMID- 1347161
TI  - Electrochemical monitoring of brain ascorbic acid changes associated with
      hypoxia, spreading depression, and seizure activity.
AB  - In vivo electrochemistry has been a valuable tool in detecting real time
      neurochemical changes in extracellular fluid. Absolute selectivity has been
      difficult to achieve previously, but we report here a carbon fiber electrode and
      measurement technique which is specific for one oxidizable species: ascorbic
      acid. Ascorbic acid is highly concentrated in extra- as well as intracellular
      brain spaces, and appears to undergo dynamic changes in response to a variety of
      physiological and pathophysiological circumstances. Recent studies have
      implicated glutamatergic mechanisms which give rise to extracellular changes in
      brain ascorbate, and we confirm and extend these observations. Preliminary
      studies, directed towards examining ascorbic acid as an index and/or result of
      hypoxia, spreading depression, and seizure activity, have been undertaken and the
      results are reported herein.

PMID- 1347162
TI  - Development of the glutamate system in rabbit retina.
AB  - We have investigated two characteristics of the glutamate system in the
      developing rabbit retina. 1) Glutamate immunoreactivity was observed at birth
      within developing processes of four cell types; two of which, photoreceptors and
      ganglion cells, are known to be glutamatergic in the adult. Two other cell types,
      type A horizontal cells and amacrine cells, are immunoreactive to both glutamate
      and GABA at birth, suggesting that endogenous pools of glutamate in GABAergic
      neurons serve as precursor for GABA synthesis. Thus it appears that endogenous
      glutamate pools are present within neurons prior to synaptogenesis as part of the
      early expression of either the glutamate or GABA transmitter phenotype. 2)
      Analysis of 3H-glutamate metabolism during retinal development showed that rapid
      conversion of glutamate to glutamine does not occur until the second postnatal
      week, coincident with the expression of Muller (glial) cell activity. In the
      absence of glial metabolism in the neonate, extracellular concentrations of
      glutamate remain relatively high and are likely to have major effects on neuronal
      maturation.

PMID- 1347163
TI  - An adenosine uptake blocker, propentofylline, reduces glutamate release in gerbil
      hippocampus following transient forebrain ischemia.
AB  - In the present study, the effect of the adenosine uptake blocker, propentofylline
      (HWA 285) on the extracellular concentration of several amino acids including
      glutamate, glycine and taurine following 10 min of forebrain ischemia in gerbil
      hippocampus was investigated using in vivo microdialysis. Pretreatment with HWA
      285 (20 mg/kg i.p.) significantly reduced the extracellular concentration of
      glutamate following ischemia but did not significantly alter levels of other
      amino acids such as glycine and taurine. These findings suggest that the
      neuroprotective effect of HWA 285 may be associated with inhibition of glutamate
      release in the gerbil hippocampus.

PMID- 1347164
TI  - Mitochondrial enzymes related to glutamate and GABA metabolism in the hippocampus
      of young and aged rats: a quantitative histochemical study.
AB  - Quantitative histochemistry (scanning microphotometry) was used to determine the
      activities of the mitochondrial enzymes NAD-linked isocitrate dehydrogenase (EC
      1.1.1.41), L-glutamate dehydrogenase (EC 1.4.1.3) and GABA transaminase (EC
      2.6.1.19) in various layers of the hippocampus (middle one third) of young (3-4
      months old) and memory-impaired aged rats (28-30 months old). For comparison,
      determinations of cytochrome c oxidase (EC 1.9.3.1) as a marker for mitochondria
      and energy metabolism were also performed. The study showed that there was a
      layered reaction pattern in the hippocampus and that the cellular distribution
      and the levels of enzyme activity were different. However, the activities of the
      different enzymes (excepting GABA transaminase and cytochrome c oxidase) were
      significantly correlated in the hippocampus in both age groups. Age-dependent
      changes were only observed for NAD-linked isocitrate dehydrogenase and GABA
      transaminase (significant increases of activities in some layers of the
      hippocampus, preferentially in the terminal field of the perforant path). From
      the present study it is concluded that, 1. the enzymatic complement of
      mitochondria in neurons and glia depends upon layer specific metabolic processes
      of the hippocampus (also with respect to glutamatergic and GABAergic terminal
      fields) indicating a layer specific interaction of the enzymes studied to produce
      or catabolize glutamate and GABA, and 2. the age dependent changes of the studied
      enzymes are very restricted.

PMID- 1347165
TI  - [Taxol and ovarian adenocarcinomas].

PMID- 1347166
TI  - The use of GM-CSF and peripheral blood stem cells (PBSC) minimises haematological
      toxicity following a myeloablative course of chemo-radiotherapy.

PMID- 1347167
TI  - Drugs update. Something to help you sleep?

PMID- 1347168
TI  - The endogenous retroviral ev21 locus in commercial chicken lines and its
      relationship with the slow-feathering phenotype (K).
AB  - Provirus ev21 was found in both K- and k(+)-feathering Rhode Island Red
      commercial layers. Probe EV21-int revealed the presence of two distinct but
      similar regions, US (unoccupied site) and OS (occupied site). Restriction
      analysis showed that these regions had at least 19 kb structural homology but
      were distinguishable by ev21 proviral sequences, OS, and possibly three
      polymorphics US. The loci OS and US were both located on Chromosome Z. The k(+)
      feathering birds were found to have only one site (either OS or US) per
      individual Z chromosome, whereas K-feathering birds had at least one Z chromosome
      with both regions in cis configuration. It has been possible to show that the
      reversion to the k(+)-feathering phenotype is accompanied by the loss of either a
      US or OS region that disrupts the cis configuration in K-feathering birds.

PMID- 1347169
TI  - Sodium-sensitive, probenecid-insensitive p-aminohippuric acid uptake in cultured
      renal proximal tubule cells of the rabbit.
AB  - In the intact kidney, renal proximal tubule cells accumulate p-aminohippurate
      (PAH) via a basolateral, probenecid- and sodium-sensitive transport system.
      Primary cultures of rabbit proximal tubule cells retain sodium-glucose co
      transport in culture, but little is known about PAH transport in this system.
      Purified proximal tubule cells from a rabbit were grown in culture and assessed
      for PAH and alpha-methyl-D-glucoside uptake capacities as well as proximal tubule
      marker enzyme activities. Control PAH uptake on collagen-coated filters (20 +/- 3
      pmol/mg protein.min; n = 8) was not significantly different from uptake in the
      presence of 1 mM probenecid (19 +/- 4 pmol/mg protein.min; n = 8). Uptake from
      the basal side of the cell was 3.9 +/- 0.7 times greater than that from the
      apical side. In multi-well plate studies, the uptake was significantly reduced by
      removing sodium from the medium and stimulated by coating the wells with
      collagen. Glutarate (10 mM) had no effect on the uptake of PAH. Other
      differentiated proximal tubule characteristics were retained in culture,
      including the ability to form domes and to transport glucose by a phlorizin
      sensitive system. Phlorizin-sensitive 1 mM alpha-methyl-D-glucoside uptake was
      134 +/- 42 pmol/mg protein.min (n = 7; P less than 0.02). The proximal tubule
      marker enzymes alkaline phosphatase and gamma-glutamyltranspeptidase, increased
      in activity in the cultures after confluence. It was concluded that whereas some
      differentiated properties were retained during primary culture of rabbit proximal
      tubule cells, the PAH transport system was selectively lost or modified from that
      present in the intact kidney.

PMID- 1347170
TI  - Capsaicin-sensitive nerves modulate reactive hyperemia in rat gut.
AB  - Reactive hyperemia (RH) is a local, vascular response that occurs following
      release from mechanical occlusion of an artery, with restoration of intra
      arterial pressure. The mechanism of this postocclusion hyperemia in the gut has
      not been identified, although metabolic, myogenic, and neurogenic mediators of
      this response have been proposed. The present study was conducted to evaluate a
      possible modulatory role for sensory innervation of the intestinal vasculature in
      RH, using acute and chronic treatment with capsaicin applied in different ways.
      In anesthetized rats, the velocity of flowing blood in the gut was determined
      continuously with a pulsed Doppler velocimeter, and arterial pressure was
      determined with a transducer. The increase in calculated intestinal vascular
      conductance at the height of RH (Ch), the excess volume of blood accumulating
      during RH, and the duration of the hyperemia were also used to quantify RH after
      occluding the anterior mesenteric artery for 30, 60, and 120 sec. In the initial
      control group of rats, the maximal increases in the velocity of flowing blood
      during RH were 61 +/- 4%, 90 +/- 7%, and 129 +/- 10% of control, conductances
      were increased to 192 +/- 5%, 222 +/- 12%, and 267 +/- 15% of control, volumes
      were 3.5 +/- 0.6 ml, 7.2 +/- 0.4 ml, and 16.2 +/- 1.8 ml, and durations of
      hyperemia were 78 +/- 5 sec, 93 +/- 6 sec, and 178 +/- 7 sec, respectively, after
      each elapsed period of occlusion. Acute treatment with periarterial capsaicin
      significantly decreased peak conductances in RH by 15-35% for all occlusions
      tested and reduced both volume and duration values. Rats treated with capsaicin
      in neonatal life exhibited reduced Ch values, as did adult rats treated
      chronically with capsaicin. Both periarterial and intrajejunal treatment with
      capsaicin decreased the duration of RH. Hexamethonium increased both Ch and the
      duration of RH and tended to reverse reductions in these parameters caused by
      capsaicin. These results suggest that sensory innervation of the intestinal
      vasculature exerts a modulatory influence in the regulation of intestinal RH.

PMID- 1347171
TI  - Neuroleptic-induced changes in the anxiolytic and myorelaxant properties of
      diazepam in the rat.
AB  - Diazepam (2.0 mg/kg) was injected (IP) into rats 30 min before chlorpromazine
      (2.5, 5.0, or 10.0 mg/kg) on ten occasions. All doses of chlorpromazine enhanced
      the capacity of diazepam to increase rats' exploration of the exposed arms of an
      elevated plus-maze, an animal screening test for anxiolytic and anxiogenic
      substances. When maze testing occurred during each of the ten diazepam---
      chlorpromazine trials (after diazepam but before chlorpromazine), this
      enhancement effect appeared on Trial 6 and persisted thereafter. Haloperidol (3.0
      mg/kg, IP) changed diazepam-elicited plus-maze activity in the same manner as
      chlorpromazine; however, thioridazine (10.0 mg/kg) and pimozide (2.0 mg/kg) were
      ineffective. Additionally, haloperidol, like chlorpromazine, was found to reduce
      diazepam's muscle relaxation effect (inclined plane test) as a consequence of
      diazepam----haloperidol pairings; once again, thioridazine and pimozide proved
      ineffective. These results suggested that not all neuroleptics will alter
      diazepam activity, and also that dopamine blockade per se is not sufficient to
      induce such changes. While the reasons for the enhanced plus-maze effects of
      diazepam induced by haloperidol and chlorpromazine remain elusive, the diminished
      myorelaxant effect may be linked to a neuroleptic's capacity to induce muscular
      side effects: thioridazine and pimozide are far less likely to yield such effects
      than are chlorpromazine and haloperidol. Haloperidol administered chronically by
      itself was found to have an effect on diazepam-induced myorelaxation.
      Administration of this butyrophenone either orally (2.0 mg/kg daily for 22 days)
      or in depot form (haloperidol decanoate, 60.0 mg/kg IM once a month for four
      months) caused a diminished effect of diazepam in rats subjected to the inclined
      plane test.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347172
TI  - Locomotor bias produced by intra-accumbens injection of dopamine agonists and
      antagonists.
AB  - Several experiments have shown that the dopamine (DA) receptors in the nucleus
      accumbens control the intensity of locomotor activity; however, there are several
      contradictory results concerning the role of the accumbens in the regulation of
      the direction of locomotion. To further evaluate the contribution of dopaminergic
      function in the accumbens to the direction of locomotion, we first compared the
      effect on the direction of locomotor activity of unilateral intra-accumbens
      injections of the nonspecific DA antagonist haloperidol, the specific D-1
      antagonist SCH-23390, the specific D-2 antagonist metoclopramide. In the second
      part of the experiment, we examined the effect on the direction of locomotor
      activity of unilateral intra-accumbens injections of the non-specific DA agonist
      apomorphine, the specific D-1 agonist SKF-38393, the specific D-2 agonist LY
      171555, and the combination of SKF-38393 and LY-171555. Haloperidol,
      metoclopramide and to a lesser extent, SCH-23393 together with peripheral
      amphetamine injections produced a locomotor bias that resulted in ipsilateral
      turning. Apomorphine, LY-171555 or the combination of SKF-38393 and LY-171555
      (but not SKF-38393 alone) produced a locomotor bias that resulted in
      contralateral turning. No significant locomotor bias was produced by intra
      accumbens injection of the various vehicles. These results suggest that the
      bilateral DA organization thought to exist in the nigro-striatal pathway for the
      control of locomotion may also be true for the mesolimbic dopamine system.

PMID- 1347173
TI  - Sigma ligand-induced emesis in the pigeon.
AB  - Pigeons were fed a fixed amount of grain-based feed and behavior was observed
      after administration of doses of ditolyguanidine (DTG), (+)-3-(3-hydroxyphenyl)-N
      (1-propyl)-piperidine [(+)-3-PPP], dextromethorphan, haloperidol, (+)-N
      allylnormetazocine (NANM), alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1
      piperazine-butanol (BMY-14802) apomorphine, pentobarbital, propranolol, and MK
      801. Of the drugs tested, DTG, dextromethorphan, and (+)-3-PPP each produced dose
      related increases in the percentage of pigeons exhibiting an emetic response. The
      emetic response produced by DTG was antagonized by haloperidol and BMY-14802 but
      not by propranolol. These observations suggest that the emetic response in the
      pigeon may be mediated by sigma sites and is unlikely to be mediated by
      phencyclidine receptors.

PMID- 1347174
TI  - Remoxipride, a specific D2 dopamine antagonist: an examination of its self
      administration liability and its effects on d-amphetamine self-administration.
AB  - The self-administration liability of remoxipride, a specific dopamine D2
      antagonist, by laboratory rats was evaluated using an intravenous self
      administration paradigm. It was observed that remoxipride failed to support self
      administration behavior across the three doses tested. In addition, remoxipride
      pretreatment attenuated d-amphetamine self-administration. The findings of the
      present study provide support for the notion that remoxipride appears to have
      functional similarity in self-administration paradigms as other D2 antagonists.

PMID- 1347175
TI  - A lever-release version of the conditioned avoidance response paradigm: effects
      of haloperidol, clozapine, sulpiride, and BMY-14802.
AB  - Rats trained on a lever-release version of the conditioned avoidance response
      (CAR) task were used to test the behavioral effects of established and putative
      antipsychotic drugs. Baseline CAR latencies decreased as the conditioned
      unconditioned stimulus interval was shortened from 500 to 250 ms. Haloperidol,
      clozapine, and BMY-14802 decreased successful avoidance responses and increased
      avoidance latencies in a dose-dependent manner without affecting the latency of
      escape responses. In contrast, sulpiride failed to affect either successful
      avoidance response rates or avoidance latency. Sulpiride, however, significantly
      attenuated d-amphetamine-induced locomotion and rearing compared to vehicle
      treated controls. Similar effects of these antipsychotics have been reported on
      shuttlebox avoidance, and these results now are confirmed in a CAR paradigm that
      achieves greater control over behavior. Because this paradigm elicits a discrete
      forelimb response without activating numerous muscle groups, it is potentially
      useful as a tool for examining neuronal mechanisms underlying the behavioral
      effects of antipsychotic drugs.

PMID- 1347176
TI  - Effect of altering dopamine or serotonin neurotransmitters upon cathinone
      discrimination.
AB  - Rats were trained to discriminate between the stimulus properties of 0.8 mg/kg l
      cathinone and its vehicle in a two-lever, food-motivated operant task. Once
      trained, rats showed a dose-related decrease in discriminative performance when
      tested with lower cathinone doses. An analysis of the dose-response curve
      indicated an ED50 value of 0.23 mg/kg. Pretreatment with CGS 10746B (5-20 mg/kg)
      resulted in a dose-related decrease in cathinone discrimination with the highest
      dose blocking cathinone discrimination. In contrast to the ability of this
      dopamine release inhibitor to decrease cathinone discrimination, pretreatment
      with three doses of the calcium channel blocker isradipine (2.5-10 mg/kg) or with
      the 5-HT3 antagonist MDL 72222 (0.1-0.4 mg/kg) had no effect upon cathinone
      discrimination. The results suggest that cathinone controls differential
      responding in a discriminative stimulus task by a mechanism involving presynaptic
      release of dopamine, which may not be regulated by either neuronal calcium influx
      through L-type calcium channels or by serotonergic neurons.

PMID- 1347177
TI  - Chronic effects of nicotine on mesolimbic dopaminergic system in rats.
AB  - Rats were pretreated with saline or nicotine (1.5 mg/kg/day) by subcutaneously
      implanting each animal with an Alzet osmotic minipump which continuously released
      saline or nicotine (1.5 mg/kg/day) for 14 days. The behavioral and biochemical
      effects of nicotine on the dopaminergic neuronal system in rat nucleus accumbens
      were examined. It was found that chronic nicotine treatment increased the
      affinity of L-[3H]nicotine binding site in the nucleus accumbens. This treatment
      also potentiated the ability of (+)-amphetamine, but not high potassium, to
      stimulate formation and release of [3H]dopamine in tissue slices from rat nucleus
      accumbens. Chronic nicotine treatment did not alter the characteristics of
      [3H]spiperone binding site, the rate of dopamine turnover and the concentrations
      of gamma-aminobutyric acid in the nucleus accumbens.

PMID- 1347178
TI  - Evidence of hyperglycemic hyperalgesia by quinpirole.
AB  - Male albino rats were tested for antinociception following injections (IP) with
      saline, quinpirole (Quin) (1 mg/kg), morphine sulfate (M.S.) (5 mg/kg), or both
      Quin and M.S. (1 mg/kg and 5 mg/kg, respectively). Quin reduced and M.S.
      increased tail-flick latency as compared to controls. Tail-flick latencies of the
      animals injected with both drugs were significantly reduced as compared M.S.
      alone. Quin increased blood glucose levels by 96 percent, as compared to saline
      controls. In competitive binding studies Quin displaced 3H-DAGO (IC50 = 29.8
      microM). CD-1 mice demonstrated a naloxone-reversible analgesia following ICV
      Quin (100 micrograms). These data are consistent with the hypothesis that the
      hyperglycemic effects of Quin attenuate M.S. analgesia while the antinociceptive
      effects of Quin may be mediated through opioid receptors.

PMID- 1347179
TI  - Ontogeny of the distribution and colocalization of calbindin D28K within neural
      and endocrine cells of the gastrointestinal tract of fetal and neonatal sheep.
AB  - Using immunocytochemical techniques we have demonstrated that Calbindin D28K
      (CaBP) is present in the gastrointestinal tract of ovine fetuses early in
      development (by day 45). At day 45, CaBP was limited to neuronal elements in the
      developing intestine. By day 100, CaBP immunoreactivity was abundant in both
      epithelial endocrine cells and nerves of the submucous and myenteric ganglia. The
      location of CaBP containing cells and fibers was similar in duodenal sections
      taken from day 100 and term (145 days), as well as those taken from 24-48 h
      postnatal lambs. CaBP is colocalized in endocrine cells containing gastrin,
      glucagon, somatostatin and neurotensin, but not glucose dependent insulinotrophic
      peptide (GIP). Furthermore, it is extensively colocalized in nerve fibers and
      cells containing neurotensin but not somatostatin or vasoactive intestinal
      peptide. The colocalization of CaBP within various endocrine and nerve cells does
      not change in fetal sheep over the last one-third of gestation and there is no
      difference between fetal and neonatal sheep.

PMID- 1347180
TI  - Research Consortium. 1992 AAHPERD National Convention, Indianapolis. Abstracts.

PMID- 1347181
TI  - Paraquat damage of rat liver mitochondria by superoxide production depends on
      extramitochondrial NADH.
AB  - Pure rat liver heavy mitochondrial fractions, in which the absence of significant
      microsomal contamination was confirmed by electron microscopy and by the lack of
      glucose-6-phosphatase activity, were used to demonstrate the effect of paraquat
      on mitochondrial ultrastructure in the presence of external NADH. Starved
      mitochondria (orthodox conformation) did not show O2 uptake or structural injury
      from either paraquat alone or NADH alone. Marked O2 uptake and structural
      breakage occurred only when paraquat and NADH were added in combination. These
      alterations were resistant to rotenone and malate plus glutamate or NADPH could
      not substitute for NADH. Paraquat was reduced anaerobically by the mitochondria
      in the presence of NADH, but not of NADPH. The addition of superoxide dismutase,
      ferricytochrome c or p-benzoquinone protected against the breakage of
      mitochondria caused by paraquat plus NADH. These results demonstrate that
      mitochondria may produce paraquat radicals in the presence of extramitochondrial
      NADH and thus generate superoxide anion radicals, resulting in structural injury
      to the mitochondria, by mechanisms that may involve the mitochondrial outer
      membrane rather than the electron transfer chain. These mitochondrial mechanisms
      in paraquat toxicity seemed to be more probable in vivo than are microsomal
      mechanisms; the latter are postulated to function in detoxication because
      phenobarbital diminished paraquat toxicity and SKF 525-A or cobaltous ions
      enhanced the toxicity.

PMID- 1347182
TI  - Effects of low-level lead exposure on hypothalamic hormones and serum
      progesterone levels in pregnant guinea pigs.
AB  - Pregnant guinea pigs were given a daily oral dose of 0, 5.5, or 11 mg lead (as
      lead acetate) per kg body weight during days 22-52 or 22-62 of gestation.
      Maternal serum progesterone levels were measured at the end of treatment, as well
      as hypothalamic levels of gonadotropin-releasing hormone (GnRH) and somatostatin
      (SRIF) in both the mothers and fetuses. Lead-treated dams had lower serum
      concentrations of progesterone at the end of treatment than did vehicle-treated
      animals. This effect was statistically significant for the higher Pb dose only.
      Hypothalamic levels of GnRH and SRIF were reduced in a dose-dependent manner by
      lead treatment in both dams and fetuses. The reduction of SRIF levels in 52-day
      old fetuses was particularly severe (92%) in the 11 mg group. However, neither
      litter size nor body and organ weights, including placental weight, of the dams
      and fetuses was significantly affected. The relevance of these hormonal decreases
      is unknown, but could include decreased reproductive capacity in both the dams
      and fetuses that does not become apparent until later in the life-cycle.

PMID- 1347183
TI  - Immunosuppression using a monoclonal antibody to ICAM-1 in murine
      allotransplantation.

PMID- 1347184
TI  - Monocyte hemolytic activity as an immunologic indicator of allograft rejection in
      rat skin transplantation.

PMID- 1347185
TI  - Calcium antagonist therapy prevents chronic cyclosporine nephrotoxicity after
      renal transplantation: a prospective study.

PMID- 1347186
TI  - [New antipsychotic drugs. Pharmacology, therapeutic effect and adverse effects].

PMID- 1347187
TI  - Spindle cell haemangioendothelioma: probably a benign vascular lesion not a low
      grade angiosarcoma. A clinicopathological, ultrastructural and
      immunohistochemical study.
AB  - Ten cases of spindle cell haemangioendothelioma (SCH) were analysed
      clinicopathologically, including an immunohistochemical survey of seven cases and
      ultrastructural observations on one. There were seven females and three males,
      ranging from 16 to 76 years of age. All but one lesion developed on the
      extremities, predominantly on the hands and feet. Six of the ten patients
      presented multiple nodules or papules which gradually increased in size and
      number over a long duration. Among them, four patients had undergone operations
      twice or more, but no metastatic foci were recognized. Histologically, the
      lesions were composed of dilated vascular spaces and a proliferation of bland
      appearing spindle cells and interspersed epithelioid endothelial cells.
      Ultrastructural and immunohistochemical studies demonstrated that the spindle
      cells were mainly made up of fibroblastic cells admixed with pericyte-like cells
      and macrophages. Smooth muscle cells and primitive mesenchymal cells were also
      present. The clinical and microscopic features suggest that SCH may be a benign
      vasoformative lesion of a heterochronological multicentric origin.

PMID- 1347188
TI  - Somatostatin cells in human somatotropic adenomas.
AB  - Data from our group have shown that the human adenomatous and normal anterior
      pituitary may be the source of somatostatin (SRIH). SRIH-producing cells were
      identified in two somatotropic adenomas. Immunoreactive SRIH cells were present
      in both cases. In case 2, material was available for RNA studies, in situ
      hybridization and electron microscopy. The size of the transcript identified by
      Northern blot analysis was identical to that of hypothalamic SRIH mRNA. In situ
      hybridization showed that the SRIH gene was expressed in a cell subset
      superimposable to that identified by immunocytochemistry. Co-localization studies
      revealed that SRIH and growth hormone (GH) immunoreactivities were not present in
      the same cells. Ultrastructural immunogold labelling showed that SRIH cells had
      features distinct from those of the somatotropes. The results confirm that the
      somatotropic adenomas have the ability to synthesize SRIH, indicate that SRIH
      expression is restricted to a subset of adenoma cells different from GH-producing
      cells, and imply that SRIH cells are involved in paracrine regulation of
      neighbouring somatotropes.

PMID- 1347189
TI  - Preparation of candidate vaccinia-vectored vaccines for haemorrhagic fever with
      renal syndrome.
AB  - Two vaccinia-vectored candidate vaccines for haemorrhagic fever with renal
      syndrome were prepared by inserting cDNA, representing the medium (M) genome
      segment, or the M and the small (S) genome segments of Hantaan virus into the
      thymidine kinase gene of the Connaught vaccine strain of vaccinia virus. In the
      single recombinant, the M segment was placed under control of the vaccinia virus
      7.5 kDa promoter. In the double recombinant, the M and S segments were placed
      under control of the vaccinia virus 7.5 kDa and 11 kDa promoters, respectively.
      An immunoplaque assay technique was developed to select recombinants without the
      need for expression of irrelevant genes or use of potential mutagens. Proteins
      indistinguishable from authentic viral envelope glycoproteins and nucleocapsid
      protein were observed by immunoprecipitation with antibodies to Hantaan virus.
      The recombinant expressing both the M and the S segments was selected for further
      development and testing as a human vaccine.

PMID- 1347190
TI  - The age-dependent risk of postvaccination complications in vaccinees with
      smallpox vaccine.
AB  - The use of vaccinia virus in recombinant systems may result in the occurrence of
      complications observed following smallpox vaccination. The results are presented
      of a large survey carried out in the USSR between 1968 and 1979. High
      complication rates are reported, particularly in older primary vaccinees; for
      example, there were 312.5 cases of neurological complications per million in
      those aged greater than or equal to 5 years. The author concludes that this
      factor will limit the use of vaccinia virus in recombinant technology.

PMID- 1347191
TI  - Epidural bupivacaine, sufentanil or the combination for post-thoracotomy pain.
AB  - Analgesia with epidural bupivacaine, sufentanil or the combination was studied in
      50 patients who had undergone thoracotomy. During operation all patients received
      an initial dose of bupivacaine 0.5% with adrenaline 5 micrograms.ml-1 (5-10 ml)
      by thoracic epidural catheter. One hour later the patients were divided into
      three groups: the bupivacaine group (bupivacaine 0.125%), the sufentanil group
      (50 micrograms sufentanil in 60 ml normal saline) and the combination group (50
      micrograms sufentanil in 60 ml bupivacaine 0.125%). Analgesia in the three groups
      was provided by a continuous epidural infusion (5-10 ml.h-1) for 3 days. The mean
      dose of bupivacaine was significantly higher (P less than 0.05) in the
      bupivacaine group (12.07 mg.h-1 (s.e.mean 0.97 mg.h-1)), compared with the
      combination group (9.82 mg.h-1 (s.e.mean 0.43 mg.h-1)). The mean dose of
      sufentanil in the sufentanil group was similar to the combination group (6.37
      micrograms.h-1 (s.e.mean 0.23 micrograms.h-1) and 6.52 micrograms.h-1 (s.e.mean
      0.28 micrograms.h-1), respectively. The pain scores on the inverse visual
      analogue scale of most patients in the bupivacaine group were unacceptably low.
      The sufentanil group had much better pain scores, but on exercise these patients
      experienced more pain than the combination group. The combination group had,
      overall, better pain scores. In the combination group, there were better
      respiratory results.

PMID- 1347192
TI  - The meiotic stage of nondisjunction in trisomy 21: determination by using DNA
      polymorphisms.
AB  - We have studied DNA polymorphisms at loci in the pericentromeric region on the
      long arm of chromosome 21 in 200 families with trisomy 21, in order to determine
      the meiotic origin of nondisjunction. Maintenance of heterozygosity for parental
      markers in the individual with trisomy 21 was interpreted as resulting from a
      meiosis I error, while reduction to homozygosity was attributed to a meiosis II
      error. Nondisjunction was paternal in 9 cases and was maternal in 188 cases, as
      reported earlier. Among the 188 maternal cases, nondisjunction occurred in
      meiosis I in 128 cases and in meiosis II in 38 cases; in 22 cases the DNA markers
      used were uninformative. Therefore meiosis I was responsible for 77.1% and
      meiosis II for 22.9% of maternal nondisjunction. Among the 9 paternal
      nondisjunction cases the error occurred in meiosis I in 2 cases (22.2%) and in
      meiosis II in 7 (77.8%) cases. Since there was no significant difference in the
      distribution of maternal ages between maternal I error versus maternal II error,
      it is unlikely that an error at a particular of maternal ages between maternal I
      error versus maternal II error, it is unlikely that an error at a particular
      meiotic stage contributes significantly to the increasing incidence of Down
      syndrome with advancing maternal age. Although the DNA polymorphisms used were at
      loci which map close to the centromere, it is likely that rare errors in meiotic
      origin assignments may have occurred because of a small number of crossovers
      between the markers and the centromere.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347193
TI  - A genetic linkage map of human chromosome 21: analysis of recombination as a
      function of sex and age.
AB  - A genetic linkage map of human chromosome 21 has been constructed using 22
      anonymous DNA markers and five complementary DNAs (cDNAs) encoding the amyloid
      beta protein precursor (APP), superoxide dismutase 1 (SOD1), the ets-2 proto
      oncogene (ETS2), the estrogen inducible breast cancer locus (BCEI), and the
      leukocyte antigen, CD18 (CD18). Segregation of RFLPs detected by these DNA
      markers was traced in the Venezuelan Reference Pedigree (VRP). A comprehensive
      genetic linkage map consisting of the 27 DNA markers spans 102 cM on the long arm
      of chromosome 21. We have confirmed our initial findings of a dramatically
      increased rate of recombination at the telomere in both females and males and of
      significantly higher recombination in females in the pericentromeric region. By
      comparing patterns of recombination in specific regions of chromosome 21 with
      regard to both parental sex and age, we have now identified a statistically
      significant downward trend in the frequency of crossovers in the most telomeric
      portion of chromosome 21 with increasing maternal age. A less significant
      decrease in recombination with increasing maternal age was observed in the
      pericentromeric region of the chromosome. These results may help in ultimately
      understanding the physical relationship between recombination and nondisjunction
      in the occurrence of trisomy 21.

PMID- 1347194
TI  - Friedreich ataxia in Louisiana Acadians: demonstration of a founder effect by
      analysis of microsatellite-generated extended haplotypes.
AB  - Eleven Acadian families with Friedreich ataxia (FA) who were from southwest
      Louisiana were studied with a series of polymorphic markers spanning 310 kb in
      the D9S5-D9S15 region previously shown to be tightly linked to the disease locus.
      In particular, three very informative microsatellites were tested. Evidence for a
      strong founder effect was found, since a specific extended haplotype spanning 230
      kb from 26P (D9S5) to MCT112 (D9S15) was present on 70% of independent FA
      chromosomes and only once (6%) on the normal ones. There was no evident
      correlation between haplotypes and clinical expression. The typing of an
      additional microsatellite (GS4) located 80 kb from MCT112 created a divergence of
      the main FA-linked haplotype, generating four minor and one major haplotype. A
      similar split was observed with GS4 in a patient homozygous for a rare 26P-to
      MCT112 haplotype. These results suggest that GS4 is flanking marker for the
      disease locus, although other interpretations are possible.

PMID- 1347195
TI  - Assignment of a gene (NEMI) for autosomal dominant nemaline myopathy to
      chromosome I.
AB  - Nemaline myopathy (NEM) is a neuromuscular disorder characterized by the
      presence, in skeletal muscle, of nemaline rods composed at least in part of alpha
      actinin. A candidate gene and linkage approach was used to localize the gene
      (NEM1) for an autosomal dominant form (MIM 161800) in one large kindred with 10
      living affected family members. Markers on chromosome 19 that were linked to the
      central core disease gene, a marker at the complement 3 locus, and a marker on
      chromosome 1 at the alpha-actinin locus exclude these three candidate genes. The
      family was fully informative for APOA2, which is localized to 1q21-q23. NEM1 was
      assigned to chromosome 1 by close linkage for APOA2, which is localized to 1q21
      q23. NEM1 was assigned to chromosome 1 by close linkage to APOA2, with a lod
      score of 3.8 at a recombination fraction of 0. Recombinants with NGFB (1p13) and
      AT3 (1q23-25.1) indicate that NEM1 lies between 1p13 and 1q25.1. In total, 47
      loci were investigated on chromosomes 1, 2, 4, 5, 7-11, 14, 16, 17, and 19, with
      no indications of significant linkage other than to markers on chromosome 1.

PMID- 1347196
TI  - Involvement of multiple chromosome 17p loci in medulloblastoma tumorigenesis.
AB  - Loss of heterozygosity for sequences located on chromosome 17p in several tumor
      types is often associated with mutations in the tumor suppressor gene p53. We
      previously showed consistent deletion of chromosome 17p12-13.1 in
      medulloblastoma, a common childhood brain tumor. Using denaturing gradient gel
      electrophoresis and direct sequencing, we have detected p53 mutations in only two
      of 20 medulloblastoma specimens. Moreover, additional RFLP studies of these 20
      specimens showed loss of heterozygosity at a more distal and distinct site,
      17p13.3. Deletion of 17p almost invariably signified a negative prognosis. Our
      results suggest that p53 mutations may contribute to the pathogenesis of
      medulloblastoma in relatively few cases. The consistent deletion of other
      discrete loci on 17p suggests that additional or alternative tumor suppressor
      genes may contribute to the tumor's phenotype.

PMID- 1347198
TI  - Discriminatory effects of protein kinase inhibitors and calcium ionophore on
      endothelial ICAM-1 induction.
AB  - Intercellular adhesion molecule 1 (ICAM-1) is a proinflammatory adhesion
      glycoprotein induced by cytokines such as interleukin-1 beta (IL-1 beta) and
      tumor necrosis factor-alpha (TNF-alpha) as well as lipopolysaccharide (LPS).
      Little is known, however, concerning the intracellular regulatory mechanisms that
      modulate ICAM-1 expression in endothelial cells. We probed the involvement of
      protein kinase function and intracellular calcium ion upon ICAM-1 expression of
      human umbilical vein endothelial cells activated alternatively by TNF-alpha, IL-1
      beta, LPS, or phorbol 12-myristate 13-acetate (PMA). Methodologies for the
      detection of ICAM-1 included both enzyme-linked immunosorbent assay and
      immunoprecipitation from biosynthetically labeled cells. The protein kinase
      inhibitor H-7 blocked induction of ICAM-1 by all of the activators; nonlinear
      regression analysis revealed 50% inhibitory concentration (IC50) values of 6-10
      microM. Another kinase inhibitor, HA1004, did not block expression of the
      adhesion molecule at concentrations up to 50 microM. In contrast, the kinase
      inhibitor staurosporine dose dependently inhibited ICAM-1 expression triggered by
      PMA (IC50 67 +/- 4 nM) but, at similar concentrations, did not inhibit ICAM-1
      expression induced by the other inflammatory stimuli. The divalent cation
      ionophore ionomycin (0.5 microM) interacted synergistically with PMA but not with
      cytokines or LPS in upregulating ICAM-1. We conclude from these data that
      although PMA-induced ICAM-1 expression may be triggered through activation of
      protein kinase C, ICAM-1 induction by IL-1 beta, TNF-alpha, or LPS may involve
      distinct regulatory pathway(s).

PMID- 1347197
TI  - Strong allelic association between the torsion dystonia gene (DYT1) andloci on
      chromosome 9q34 in Ashkenazi Jews.
AB  - The DYT1 gene responsible for early-onset, idiopathic torsion dystonia (ITD) in
      the Ashkenazi Jewish population, as well as in one large non-Jewish family, has
      been mapped to chromosome 9q32-34. Using (GT)n and RFLP markers in this region,
      we have identified obligate recombination events in some of these Jewish
      families, which further delineate the area containing the DYT1 gene to a 6-cM
      region bounded by loci AK1 and ASS. In 52 unrelated, affected Ashkenazi Jewish
      individuals, we have found highly significant linkage disequilibrium between a
      particular extended haplotype at the ABL-ASS loci and the DYT1 gene. The 4/A12
      haplotype for ABL-ASS is present on 69% of the disease-bearing chromosomes among
      affected Jewish individuals and on only 1% of control Jewish chromosomes (chi 2 =
      91.07, P much less than .001). The allelic association between this extended
      haplotype and DYT1 predicts that these three genes lie within 1-2 cM of each
      other; on the basis of obligate recombination events, the DYT1 gene is
      centromeric to ASS. Furthermore, this allelic association supports the idea that
      a single mutation event is responsible for most hereditary cases of dystonia in
      the Jewish population. Of the 53 definitely affected typed, 13 appear to be
      sporadic, with no family history of dystonia. However, the proportion of sporadic
      cases which potentially carry the A12 haplotype at ASS (8/13 [62%]) is similar to
      the proportion of familial cases with A12 (28/40 [70%]). This suggests that many
      sporadic cases are hereditary, that the disease gene frequency is greater than
      1/15,000, and that the penetrance is lower than 30%, as previously estimated in
      this population. Most affected individuals were heterozygous for the ABL-ASS
      haplotype, a finding supporting autosomal dominant inheritance of the DYT1 gene.
      The ABL-ASS extended-haplotype status will provide predictive value for carrier
      status in Jewish individuals. This information can be used for molecular
      diagnosis, evaluation of subclinical expression of the disease, and elucidation
      of environmental factors which may modify clinical symptoms.

PMID- 1347199
TI  - Effect of somatostatin on mesenteric vascular resistance in normal and portal
      hypertensive rats.
AB  - Vasoactive effects of natural somatostatin (SRIF-14) and its analogue octreotide
      were studied in in vitro perfused superior mesenteric arterial beds of normal
      (Sham) and portal hypertensive (PVL) rats. Tested concentrations covered the
      whole range used in clinical settings (10(-10) to 10(-5) M for SRIF-14 and 10(
      11) to 10(-6) M for octreotide, respectively). Vessel resistances only minimally
      changed to infusions of SRIF-14 (from 3.5 +/- 0.4 to 3.7 +/- 0.5 mmHg.ml-1.min
      and 3.8 +/- 0.3 to 3.9 +/- 0.4 mmHg.ml-1.min for PVL and Sham) and octreotide
      (from 3.3 +/- 0.2 to 3.4 +/- 0.4 mmHg.ml-1.min and 3.8 +/- 0.4 to 4.0 42- 0.4
      mmHg.ml-1.min for PVL and Sham). The same was true for bolus injections. In
      contrast, norepinephrine induced significant increases in vessel resistance (up
      to 110.6 +/- 20.1 mmHg.ml-1.min). In conclusion, SRIF-14 and octreotide exert no
      direct effect on vascular smooth muscle tone in splanchnic resistance vessels of
      Sham and PVL rats. The vasoconstriction reported in vivo seems therefore probably
      mediated by the ability of these peptides to inhibit the secretion of
      vasodilatatory substances.

PMID- 1347200
TI  - Alpha 1-adrenergic signaling in human airway epithelial cells involves inositol
      lipid and phosphate metabolism.
AB  - A role for phospholipase C (PLC) hydrolysis of phosphatidylinositol 4,5
      bisphosphate (PIP2) as a mechanism of alpha 1-adrenergic signal transduction in
      human airway epithelial cells (AEC) was investigated in isolated normal tracheal
      and cystic fibrosis (CF) nasal epithelial cells grown in in vitro culture and
      prelabeled with 3 muCi myo-[3H]inositol/ml for 72 h. Breakdown of
      polyphosphoinositides was measured using thin-layer chromatography to detect
      phosphatidylinositol, phosphatidylinositol 4-phosphate (PIP), and PIP2. Inositol
      phosphates were separated by ion-exchange column chromatography. In normal AEC,
      the addition of the endogenous catecholamine l-epinephrine produced a rapid,
      transient accumulation of inositol 1,4,5-trisphosphate (IP3) and inositol 1,4
      bisphosphate (IP2) and breakdown of PIP and PIP2. IP3 increased 1.7-fold and IP2
      1.6-fold after 20 and 40 s, respectively. A maximal decrease of 35% PIP2 and 30%
      PIP is observed after 20 and 40 s, respectively. The effects of l-epinephrine
      were not blocked by the beta-adrenergic antagonist dl-propranolol but were
      mimicked by the alpha 1-adrenergic agonist methoxamine. Prazosin, an alpha 1
      adrenergic antagonist, and pertussis toxin (PTX) blocked the effects of l
      epinephrine and methoxamine. Addition of l-epinephrine and methoxamine to CF
      nasal epithelial cells also induced prazosin-sensitive polyphosphoinositide
      breakdown and inositol phosphate accumulation. A 2.2-fold accumulation of IP3 was
      observed after 10 s and 2.0-fold increase in IP2 after 20 s. Maximal decreases of
      32% PIP2 and 23% PIP levels were observed after 20-s incubation with l
      epinephrine. PTX reduced the effects of l-epinephrine and significantly blocked
      the effects of methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347202
TI  - Effects of alpha 1-adrenergic blockade on intrarenal hemodynamics in heart
      failure rats.
AB  - To investigate intrarenal hemodynamics and effects of alpha 1-adrenergic blockade
      on glomerular functions in congestive heart failure (CHF), micropuncture studies
      were performed before and after intravenous injection of terazosin (1
      microgram/100 g body wt iv) in eight myocardial infarction (MI) and in nine sham
      operated rats after intraperitoneal injection of Inactin (70 mg/kg). CHF was
      characterized by elevated left ventricular end-diastolic pressure and increased
      total heart weight. In CHF rats, single nephron glomerular filtration rate
      (SNGFR), single nephron plasma flow (SNPF), and ultrafiltration coefficient (Kf)
      were decreased compared with sham-operated rats (SNGFR, 21.9 +/- 1.6 vs. 39.2 +/-
      2.9 nl.min-1.g-1, P less than 0.01; SNPF, 66.6 +/- 6.1 vs. 133.8 +/- 10.5 nl.min
      1.g-1, P less than 0.01; Kf, 0.019 +/- 0.001 vs. 0.041 +/- 0.004 nl.s-1.mmHg-1.g
      1, P less than 0.01). Single nephron filtration fraction (SNFF), glomerular
      pressure (Pg), and efferent arteriolar resistance (Re) were higher in the CHF-MI
      rats than in the sham-operated rats (SNFF, 33.4 +/- 1.3 vs. 27.7 +/- 1.0, P less
      than 0.05; Pg, 60.2 +/- 1.6 vs. 53.3 +/- 0.8 mmHg, P less than 0.01; Re, 3.92 +/-
      0.66 vs. 1.62 +/- 0.15 x 10(10) dyn.s.cm-5.g, P less than 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1347201
TI  - Characterization of coronary vasoconstriction produced by rostral ventrolateral
      medulla stimulation in rats.
AB  - Previous studies have demonstrated that coronary vasoconstriction can be produced
      by activation of specific central nervous system sites in the cat. The present
      study was undertaken 1) to develop a rat model for studying central influences on
      coronary circulation and 2) to utilize this model for characterization of the
      changes in coronary blood flow (CBF) produced by stimulation of rostral
      ventrolateral medulla (RVLM). Electrical stimulation of right RVLM in chloralose
      anesthetized rats with bilateral vagotomy produced a transient decrease in CBF
      followed by an increase in CBF concomitant with a decrease in hindquarter blood
      flow, a pressor response, and tachycardia. After atenolol the tachycardia and
      increase in CBF were abolished, whereas the decrease in CBF was enhanced and
      prolonged. Phentolamine (1 mg/kg iv) or removal of the stellate ganglia inhibited
      the decrease in CBF but did not totally abolish the increase in coronary vascular
      resistance. Inhibition of nitric oxide synthesis with N-nitro-L-arginine (10
      microM/kg iv) enhanced the decrease in CBF produced by stimulation in RVLM. These
      results indicate that, in rat model, the centrally induced decrease in CBF is 1)
      mediated by cardiac sympathetic innervation but only partially through alpha
      adrenoceptors and 2) enhanced by removal of the inhibitory effect of the
      endothelium.

PMID- 1347203
TI  - Area postrema stimulation induces differential renal hemodynamics with two
      anesthetics.
AB  - The effect of area postrema stimulation (APS) on blood pressure, renal blood flow
      (RBF), and renal vascular resistance was compared in urethan-anesthetized and
      pentobarbital sodium-anesthetized Sprague-Dawley rats. Mean arterial pressure
      (MAP) increased in a frequency-dependent manner during APS in both urethan- and
      pentobarbital-anesthetized rats. Although no significant differences occurred in
      the maximum percent change in MAP between groups, marked differences occurred in
      RBF and calculated renal vascular resistance (RVR) changes. In urethan
      anesthetized rats, RBF and MAP increased during APS, but RVR did not change. In
      contrast, APS significantly decreased RBF (-26.5 +/- 1.9%) while increasing RVR
      (+99.4 +/- 11.4%) in pentobarbital-anesthetized rats. The increase in RVR in the
      pentobarbital-anesthetized group during APS was eliminated by prior ganglionic
      blockade. It was concluded that the anesthetic agent employed can significantly
      alter the degree to which APS can activate renal vasomotion in the rat.

PMID- 1347204
TI  - Pipecuronium versus high dose vecuronium. I. A comparison of speed of onset and
      cumulation during isoflurane anaesthesia.
AB  - The onset time and tendency to cumulation of pipecuronium and high-dose
      vecuronium were studied during nitrous oxide anaesthesia supplemented with
      isoflurane. Pipecuronium 0.06 mg.kg-1 had a similar duration of action to
      vecuronium 0.015 mg.kg-1 (42 vs 49 min). Patients who received vecuronium had a
      shorter onset time of neuromuscular blockade (p less than 0.01). The use of
      pipecuronium was associated with marked cumulation.

PMID- 1347205
TI  - Pipecuronium versus high dose vecuronium. II. A comparison of speed of onset and
      cumulation during propofol anaesthesia.
AB  - The onset time and tendency to cumulation of pipecuronium and high-dose
      vecuronium were compared during nitrous oxide anaesthesia supplemented with a
      propofol infusion. Pipecuronium 0.06 mg.kg-1 had a similar duration of action to
      vecuronium 0.2 mg.kg-1 (49 vs 43). Patients who received vecuronium had a shorter
      onset time of neuromuscular blockade (p less than 0.01). Neither pipecuronium nor
      vecuronium showed marked cumulation.

PMID- 1347206
TI  - Ranitidine does not have a uniquely lower affinity for cerebral H2-receptors.

PMID- 1347208
TI  - Feeding behavior, natural food, and nutritional relationships of larval
      mosquitoes.

PMID- 1347207
TI  - Changes in vitreous humor associated with postmortem interval in rabbits.
AB  - Concentrations of serum and vitreous humor constituents at time of death, and
      concentrations of vitreous humor constituents at time of death and at 7
      postmortem intervals were compared in 70 domestic, female New Zealand White
      rabbits (Oryctolagus cuniculus). Urea nitrogen concentration was significantly (P
      = 0.0094) different, but was linearly correlated in serum and vitreous humor at
      time of death and at the 4- and 8-hour postmortem intervals. Concentrations of
      gamma-glutamyltransferase were not significantly different in serum and vitreous
      humor at time of death, nor were concentrations significantly different in
      vitreous humor at time of death and at the 4-hour postmortem interval. The
      vitreous humor concentrations of glucose, triglycerides, sodium, potassium,
      cholesterol, total protein, albumin, lactate dehydrogenase, creatine kinase,
      aspartate transaminase, bilirubin, cortisol, and IgG were neither similar to nor
      predictive of serum constituents. Vitreous humor can be used as a source for
      estimates of serum urea nitrogen and gamma-glutamyltransferase up to 8 and 4
      hours after death, respectively.

PMID- 1347209
TI  - Indoor Air '90: health effects associated with indoor air contaminants.
      International Conference on Indoor Air Quality and Climate, Toronto, 1990.

PMID- 1347210
TI  - A follow-up study on short-term treatment of agoraphobia.
AB  - The differential effectiveness of three treatment packages for agoraphobia was
      tested. Patients received one of three short-term treatments: Breathing
      Retraining and Cognitive Restructuring, graded Self-Exposure in vivo, or a
      combination of both. No differential effects were found between the treatment
      conditions at posttest and at an 18 months follow-up. Improvement at follow-up
      assessment was associated with whether patients had further treatment during the
      follow-up period. No relationship was found between further improvement and
      demographic variables, pre- and posttest scores on psychological questionnaires
      or the use of medication at follow-up. Implications of these findings are
      examined.

PMID- 1347212
TI  - Effects of activin A and somatostatin on intact FSH secretion and intracellular
      Ca2+ concentration in human FSH-secreting pituitary adenoma cells.
AB  - Activin A stimulated synthesis and secretion of intact FSH in dispersed human FSH
      secreting adenoma cells. Significant stimulation was observed after 24 hr.
      Activin A caused an increase in Ca2+ concentration ([Ca2+]i). This response
      occurred soon after the activin A action. These effects were blocked in Ca(2+)
      deficient medium and by nitrendipine (5 microM). Somatostatin inhibited the
      activin A-induced intact FSH secretion and the [Ca2+]i response. These findings
      indicated that Ca2+ influx through voltage-gated Ca2+ channel was involved in the
      activin A induced synthesis and secretion of intact FSH.

PMID- 1347211
TI  - Vasoconstrictor agonists activate G-protein-dependent receptor-operated calcium
      channels in pig aortic microsomes.
AB  - Receptor-operated Ca2+ channels were characterized by their ability to decrease
      steady-state ATP-dependent Ca2+ accumulation into pig aortic microsomes. The
      vasoconstrictor agents noradrenaline, angiotensin II and adenosine 5'-[alpha beta
      methylene]triphosphate (pp[CH2]pA) all decreased Ca2+ accumulation only when
      sonicated into vesicles (to allow access to receptor sites) and in the presence
      of guanosine 5'-[beta gamma-imido]triphosphate to activate transducing G
      proteins. The effect of noradrenaline was inhibited by the alpha 2 antagonist
      yohimbine, but not by the alpha 1 antagonist prazosin. The effect of none of the
      agonists was reversed by diltiazem. SK&F 96365 (an inhibitor of receptor-mediated
      Ca2+ influx into intact cells) reversed the effect of noradrenaline, but not that
      of pp[CH2]pA, which suggests that at least two receptor-operated channels may be
      present in this preparation.

PMID- 1347213
TI  - Differential inhibition of long-chain acyl-CoA hydrolases by hypolipidemic drugs
      in vitro.
AB  - The effect of in vitro addition of three hypolipidemic drugs (clofibric acid,
      bezafibrate and gemfibrozil) on rat palmitoyl-CoA hydrolases has been studied, by
      using a spectrophotometric method (Berge RK, Biochim Biophys Acta 574: 321-333,
      1979) optimized for valoration of crude enzyme preparations. Mitochondrial and
      microsomal hepatic palmitoyl-CoA hydrolase activities were inhibited by the three
      drugs in a concentration-dependent fashion. The order of inhibitory potency was
      gemfibrozil greater than bezafibrate greater than clofibric acid, irrespective of
      the enzyme activity tested. Cytosolic rat brain palmitoyl-CoA hydrolase activity
      was not affected. Kinetic studies with gemfibrozil on the solubilized microsomal
      palmitoyl-CoA hydrolase activity point to a mixed non-competitive type of
      inhibition.

PMID- 1347214
TI  - Cytochrome aa3 depletion is the cause of the deficient mitochondrial respiration
      induced by chronic valproate administration.
AB  - Liver mitochondria from rats fed 1% (w/w) valproic acid for 75 days displayed an
      approximate 30% decrease in coupled respiration rates with substrates entering
      the respiratory chain at complexes I and II. Uncoupling the respiration from
      proton-pumping, or measuring the respiration without complex IV removed this
      inhibition. The treatment induced a loss of activity of cytochrome oxidase
      consistent with a decrease in the mitochondrial content of cytochrome aa3. The
      inhibition induced by long lasting administration of valproate is apparently
      located at the site of the proton-pumping activity of complex IV. Furthermore,
      the capacity of electron transport through complex IV, being far in excess of
      that required for normal functioning in coupled mitochondria, seems to be
      controlled by the coupling to proton-pumping in which cytochrome aa3 appears to
      play a major role.

PMID- 1347215
TI  - The third dopamine receptor (D3) as a novel target for antipsychotics.

PMID- 1347216
TI  - Comparison of opioid properties between D-Arg-containing dipeptides and
      tetrapeptides.
AB  - Since the D-Arg-containing dipeptides, H-Tyr-D-Arg-OMe (TDA) and H-Tyr(Et)-D-Arg
      OMe, and D-Arg2-substituted dermorphin N-terminal tetrapeptide analogues, H-Tyr-D
      Arg-Phe-Gly-OEt (TDAPG) and H-Tyr(Et)-D-Arg-Phe-Gly-OEt gave different
      pharmacological responses in vivo, opioid interaction and structure-activity
      relationships have been investigated in vitro. In the isolated guinea-pig ileum
      assay, the tetrapeptides were potently inhibitory, their activity markedly
      exceeding that of the dipeptides. In particular, the first tetrapeptide had twice
      the activity of morphine, while the potency of the dipeptides was less than one
      twentieth that of morphine. Also in the opioid receptor binding assay,
      tetrapeptides had a higher affinity than the dipeptides. IC50 values of
      tetrapeptides were 8.46 and 23.7 nM, respectively, which were lower than that of
      morphine. Ethylation of the Tyr residue of TDA much increased the opioid activity
      whereas that of TDAPG greatly decreased it. All peptides used were extremely
      stable to aminopeptidase-M and carboxypeptidase-Y and had an inhibitory effect on
      enkephalin (EK)-degrading enzymes. From these results, it appears that the
      effects of the tetrapeptides are due mainly to specific interaction with opioid
      receptors, whereas the dipeptides do not act specifically on the opioid
      receptors, but are involved in non-opioid mechanisms. The resistance to enzymes
      and inhibitory effect of the peptides used on the EK-degrading enzymes may also
      account for their potent and long-lasting opioid-like activities.

PMID- 1347218
TI  - Code of ethics. Issues in ethics.

PMID- 1347217
TI  - Glucocorticoid-mediated potentiation of P450 induction in primary culture of
      rainbow trout hepatocytes.
AB  - Induction of 7-ethoxyresorufin O-deethylase activity (a cytochrome P450IA
      dependent activity) by beta-naphthoflavone (0.36 microM) is increased 2-3-fold by
      dexamethasone or cortisol (10(-9)-10(-7) M) in rainbow trout hepatocyte cultures.
      This potentiation does not seem to be a time-dependent process and could be a
      classical glucocorticoid receptor-mediated event resulting in enhanced
      transcriptional activation of the CYP1A, as previously shown in mammals. Since
      glucocorticoid levels can increase in fish exposed to pollutants, such steroids
      may interfere with the induction response to xenobiotics.

PMID- 1347219
TI  - Mitochondrial complex I and II activities of lymphocytes and platelets in
      Parkinson's disease.
AB  - Mitochondrial Complex I deficiencies have been described not only in the brain
      but also in the skeletal muscle and platelets in Parkinson's disease (PD). We
      report activities of Complex I, II, III, and IV in lymphocytes and platelets in
      20 patients with PD and age-matched controls. A small but a significant decrease
      in the platelet Complex I activity was found in PD (9.14 +/- 1.86 units/mg
      protein) compared with that in the control (12.37 +/- 2.66 units/mg protein) (P =
      0.0002). The lymphocyte Complex I activity was about the same between PD and the
      control. The activity of Complex II was slightly diminished in both platelets and
      lymphocytes in PD. Rather small decrease in the platelet Complex I activity in PD
      may be clinically non-significant. But it may indicate the presence of a
      qualitatively similar abnormality in platelets as in the nigro-striatal neurons.
      The cause for decrease in the Complex II activity is unknown at this moment.
      Further studies seem necessary.

PMID- 1347220
TI  - Neurochemical markers in the cerebrospinal fluid of patients with Alzheimer's
      disease, Parkinson's disease and amyotrophic lateral sclerosis and normal
      controls.
AB  - Several neurotransmitter markers were investigated in the cerebrospinal fluid
      (CSF) from patients with Alzheimer's disease (AD) (n = 27), Parkinson's disease
      (PD) (n = 35) and ALS (n = 26) and from control subjects (n = 34) to compare the
      possible alterations in the biochemical profiles of these different
      neurodegenerative diseases. The main proportion of the patients represented an
      early phase of the illness at the time of the diagnosis. Correlations of the
      degree of dementia and the stage of the disease with CSF measures were evaluated.
      The CSF levels of somatostatin like-immunoreactivity (SLI) were significantly
      reduced in AD patients when compared with those of normals and ALS patients. The
      CSF concentrations of homovanillic acid (HVA) were significantly decreased for PD
      patients and the decrease focused on the non-demented patients. A trend of
      decreasing HVA values towards the most advanced stage of Parkinson's disease
      assessed by Webster's scale was also displayed. The content of 3-methoxy-4
      hydroxyphenylglycol (MHPG) in the CSF was higher for ALS patients than for other
      groups. The lowest 5-hydroxy-indoleacetic acid (5HIAA) levels were observed in
      the PD group and the lowest acetylcholinesterase (AChE) activities were found in
      the PD patients with the most severe disease. Changes in CSF measures were too
      subtle to be beneficial for diagnostic purposes, but adequate for reflecting the
      different neurochemical profiles of these three degenerative neurological
      disorders.

PMID- 1347221
TI  - [First International Conference on Biopsychosocial Aspects of HIV-infection.
      Amsterdam, RAI Congress Center, 22-25 September 1991].

PMID- 1347222
TI  - Variability of onset times within and among relaxant regimens.
AB  - STUDY OBJECTIVE: To evaluate the consistency of times to 95% twitch height
      depression (T95%) in groups of patients receiving identical induction and
      relaxant regimens. DESIGN: Prospective, noncontrolled, blinded study. SETTING:
      Ambulatory surgical unit at a university medical center. PATIENTS: Seventy-five
      ASA physical status I and II patients undergoing general endotracheal anesthesia.
      INTERVENTIONS: Patients received succinylcholine 1.5 mg/kg or a nondepolarizing
      regimen with doses ranging from approximately 1.5 to 6 times the ED95, with or
      without a priming dose. MEASUREMENTS AND MAIN RESULTS: For each of the eight
      relaxant regimens used in five or more patients, the intraregimen variability of
      T95% (at the adductor pollicis muscle upon ulnar stimulation at 0.1 Hz) was
      expressed as SD and range, and the individual data points were displayed. There
      was wide intraregimen variability. For each regimen, the slowest T95% was at
      least 73% longer than the fastest T95%. For the 16 patients receiving a priming
      dose plus an intubating dose 5 or more times the ED95, the median T95% was 95
      seconds; however, T95% was beyond 120 seconds in 5 of the 16 cases. CONCLUSIONS:
      The wide variability in onset times among subjects receiving the same regimen
      indicates that monitoring of neuromuscular response, preferably to a relatively
      slow rate of neurostimulation, is essential if one elects to use moderate to high
      doses of atracurium and/or vecuronium for rapid-sequence induction in a patient
      in whom movement or coughing is unacceptable. Since onset times were not
      symmetrical about the mean, the magnitude and frequency of unacceptable onset
      times would not be fully appreciated unless the individual data points were
      displayed. Such information may be critical when reporting the suitability of a
      neuromuscular blocking drug for rapid intubation.

PMID- 1347223
TI  - Comparative effects of desflurane and isoflurane on vecuronium-induced
      neuromuscular blockade.
AB  - STUDY OBJECTIVE: To evaluate the neuromuscular effects of a nondepolarizing
      muscle relaxant (vecuronium) during anesthesia with equipotent concentrations of
      either desflurane or isoflurane. DESIGN: Randomized open study comparing effects
      of desflurane and isoflurane on vecuronium-induced neuromuscular blockade.
      SETTING: University-affiliated medical center. PATIENTS: Forty-five healthy
      adults undergoing elective surgical procedures randomly assigned to receive
      either desflurane, nitrous oxide (N2O), and vecuronium or isoflurane, N2O, and
      vecuronium for maintenance of general anesthesia. INTERVENTIONS: Following a
      standardized induction sequence, patients receiving either desflurane and N2O or
      isoflurane and N2O were administered bolus doses of vecuronium equal to 0.01,
      0.02, or 0.03 mg/kg intravenously (IV) during the maintenance period.
      Neuromuscular transmission was measured using a Relaxograph monitor. MEASUREMENTS
      AND MAIN RESULTS: Vecuronium produced similar depression of neuromuscular
      function at equipotent (50% of the minimum alveolar concentration) end-tidal
      concentrations of isoflurane 0.6% and desflurane 3.0%. Following administration
      of vecuronium 0.01 to 0.03 mg/kg IV, onset times (3.4 +/- 0.4 minutes to 3.2 +/-
      0.4 minutes and 3.2 +/- 0.5 minutes to 3.0 +/- 0.6 minutes), maximum T1 twitch
      depression (80% +/- 10% to 95% +/- 9% and 81% +/- 9% to 97% +/- 10%), clinical
      duration of blockade (12 +/- 5 minutes to 20 +/- 8 minutes and 10 +/- 5 minutes
      to 19 +/- 17 minutes), and T1 recovery times (10 +/- 3 minutes to 12 +/- 6
      minutes and 10 +/- 3 minutes to 12 +/- 4 minutes) were similar in the isoflurane
      and desflurane treatment groups, respectively (means +/- SD). CONCLUSION:
      Vecuronium has similar neuromuscular effects when administered in the presence of
      desflurane 3% and isoflurane 0.6%.

PMID- 1347224
TI  - Amiloride antagonizes beta-adrenergic stimulation of cAMP synthesis and Cl-
      secretion in human tracheal epithelial cells.
AB  - Amiloride, a potent blocker of the sodium channel in airway epithelium, has been
      administered by aerosol as a therapeutic agent for cystic fibrosis. Because
      amiloride in high concentration has been reported to interfere with cell
      functions, including adrenergic responses, we tested the ability of amiloride to
      inhibit beta-adrenergic responses in human tracheal epithelial cells. Amiloride
      (10(-4) M), applied from the basolateral surface of a cell monolayer, inhibited
      the changes in transepithelial potential and short circuit current to
      isoproterenol (10(-6) M). The stimulation of cyclic adenosine monophosphate
      (cAMP) synthesis by isoproterenol was inhibited in dose-dependent fashion by
      amiloride (P = 0.007 by multivariate ANOVA with multiple samples correction).
      Amiloride did not affect baseline transepithelial potential, short circuit
      current, basal cAMP levels, cAMP response to prostaglandin E2, or basal adenylate
      cyclase activity measured directly in membrane preparations. Therefore, it is
      unlikely that amiloride exerts a nonspecific toxic effect on adenylate cyclase,
      receptor-cyclase coupling, or substrate or cofactor supply. The binding of
      [125I]iodocyanopindolol (ICYP), a beta-adrenergic receptor antagonist, to
      membranes from human tracheal epithelial cells could be displaced by amiloride
      with IC50 = 410 microM; displacement was 70% at 10(-3) M amiloride. These data
      are most consistent with the hypothesis that amiloride inhibits beta-adrenergic
      responses in airway epithelial cells by occupying beta-adrenergic receptor sites.
      Therapeutic administration of amiloride should take into account its affinity for
      adrenergic receptors.

PMID- 1347225
TI  - Reappraisal of human retroviral infection in Venezuela.

PMID- 1347226
TI  - Prevalence of HTLV infection in the Dominican Republic: association with
      neurological disease.
AB  - The presence of the human T-cell leukemia virus (HTLV) in Dominican blood donors
      and patients with tropical spastic paraparesis (TSP) was first detected in 1987.
      To define further the seroprevalence in the country, nearly 4,000 samples from
      high- and low-risk populations, as well as patients with neurological disease and
      with leukemia or lymphoma were tested for HTLV antibodies. A 1-2% seropositivity
      rate was found among the low-risk population, a 2-5% in the high-risk, and at
      least 87% in those with TSP. A few patients with malignancy also had antibodies
      to HTLV. An increase in seropositivity with age and a predominance of female
      seropositive individuals were found. Infectious virus was isolated from TSP
      patients, prostitutes, and family members of index patients. These data indicate
      the substantial level of HTLV infection in another Caribbean country and its
      relation to neurologic disease.

PMID- 1347227
TI  - HIV-1 in blood monocytes: frequency of detection of proviral DNA using PCR and
      comparison with the total CD4 count.
AB  - In vivo infection of monocytes/macrophages by the human immunodeficiency virus
      (HIV) has been investigated in many studies since these cells were suggested to
      provide a reservoir for the virus. In this study, we wanted to find out whether
      HIV provirus could be detected in circulating monocytes and whether it could be
      compared with the provirus found in T lymphocytes (T-Ly). Twenty-one seropositive
      subjects were studied. The amplification method (PCR) was used with three
      different primer pairs (in gag, env, and long terminal repeat regions of the
      viral genome) to detect the HIV-1 genome in monocytes and T-Ly separated by an
      immunomagnetic isolation technique. Of 21 monocyte samples, 13 (61.9%) were
      positive with at least one primer pair. Furthermore, the provirus harboured in 9
      of those 13 monocyte-positive samples differed, with respect to pattern of primer
      response, from the provirus found in T-Ly. When comparing primer responses of
      monocytes and T-Ly, most of the differences were found to have occurred with the
      env primers (8 of 9 cases). Dilution experiments with the 8 E5 cell line revealed
      that 9 of 12 T-Ly contained 15-150 HIV DNA copies per 150,000 cells while 8 of 11
      positive monocytes contained less than 15 copies. However, monocyte samples from
      two asymptomatic individuals and an AIDS patient showed high levels of HIV DNA,
      comparable to those obtained in T-Ly. Finally, it was also found that the
      monocyte-positive subjects were more immunosuppressed than the negative ones, as
      shown by the total CD4 count of both groups (means of 269 T4/mm3 and 573 T4/mm3,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347228
TI  - Dexmedetomidine--a powerful new adjunct to anaesthesia?

PMID- 1347229
TI  - Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and
      reduces the need for thiopentone and peroperative fentanyl.
AB  - The effects of the new, highly selective alpha 2-adrenergic agonist,
      dexmedetomidine, were studied in a randomized, placebo-controlled, double-blind
      trial in 24 ASA I patients. Dexmedetomidine 0.6 micrograms kg-1 or saline was
      given i.v. 10 min before induction of anaesthesia. The required dose of
      thiopentone was significantly (P less than 0.001) smaller in the dexmedetomidine
      group (mean 4.4 (sd 0.9) mg kg-1) than in the control group (6.9 (1.6) mg kg-1),
      and the drug attenuated the cardiovascular responses to laryngoscopy and tracheal
      intubation. The concentration of noradrenaline in mixed venous plasma was smaller
      in the dexmedetomidine group during all phases of induction (P less than 0.01).
      During surgery, fentanyl was required in a dose of 0.5 (0.6) mg kg-1 and 2.8
      (2.6) mg kg-1 in the dexmedetomidine and control groups, respectively (P less
      than 0.001). During 2 h postoperative follow-up, oxycodone 0.06 (0.06) mg kg-1
      and 0.16 (0.1) mg kg-1 (P less than 0.05) was given to the two groups
      respectively.

PMID- 1347230
TI  - The role of histamine in the cardiovascular effects of atracurium.
AB  - We have investigated the effect of a bolus injection of atracurium 0.6 mg kg-1 on
      the cardiovascular system in 16 patients undergoing aortocoronary bypass surgery.
      H1- and H2-receptor antagonists were administered to eight patients before the
      neuromuscular blocker. A standard anaesthetic was used comprising fentanyl,
      flunitrazepam, etomidate and enflurane. After administration of atracurium,
      haemodynamic changes and plasma histamine concentrations were measured at
      frequent intervals. In the first group, who received only atracurium, a brief but
      marked decrease in SVR and MAP occurred, accompanied by an increase in Cl,
      together with a marked increase in plasma concentration of histamine. In the
      second group, who received H1- and H2-receptor block, there was no decrease in
      MAP and only a small increase in plasma histamine concentration. However, there
      were significant changes in SVR and Cl similar to those in atracurium group.

PMID- 1347231
TI  - Comparison of the train-of-four fade profiles produced by vecuronium and
      atracurium.
AB  - In this double-blind study, we have allocated randomly 40 ASA I-III patients to
      one of four groups. After a standard anaesthetic induction, patients received
      vecuronium 0.08 mg kg-1 or 0.10 mg kg-1, or atracurium 0.4 mg kg-1 or 0.5 mg kg
      1. Using an electromyogram (Datex Relaxograph) the train-of-four (TOF) response
      was measured during onset of and recovery from neuromuscular block. A greater
      degree of fade of TOF was observed with atracurium during onset of neuromuscular
      block than with equivalent doses of vecuronium. During recovery of neuromuscular
      transmission, vecuronium was associated with more fade than atracurium. The
      differences in the TOF profiles of these two drugs may be important when judging
      the adequacy of antagonism of neuromuscular block using the TOF response.

PMID- 1347232
TI  - T4+ cell numbers are correlated with plasma glutamate and cystine levels:
      association of hyperglutamataemia with immunodeficiency in diseases with
      different aetiologies.
AB  - Human immunodeficiency virus type 1 (HIV-1) seropositive individuals suffer from
      a depletion of T4+ T cells and have elevated plasma glutamate levels. Glutamate
      is also elevated in cancer patients, and several authors have shown that elevated
      extracellular glutamate levels inhibit competitively the membrane transport of
      cystine and cause a decrease of intracellular cystine. We, therefore, tested the
      hypothesis that high glutamate and/or low cystine levels may generally be
      associated with low lymphocyte reactivity or low T4+ counts. In three independent
      studies we tested (i) serum amino acid levels (AAL) versus T4+ counts in healthy
      individuals, (ii) plasma AAL versus lymphocyte responses in healthy individuals,
      and (iii) plasma AAL versus T4+ counts in HIV-1 seropositive individuals. When
      the individuals in each study were divided into four subgroups as defined by
      median glutamate and cystine levels, the results showed that persons with a
      combination of low glutamate and high cystine level (LGHC subgroups) had the
      highest mean T4+ count or highest lymphocyte reactivity. Moreover, the LGHC
      subgroup in a study of lung cancer patients had a much longer mean survival time
      than the other three subgroups. In HIV-1 infected patients, hyperglutamataemia is
      associated with hypocystinaemia and hypocysteinaemia. Azidodeoxythymidine (AZT)
      treated HIV patients had, on average, lower glutamate levels than patients
      without AZT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347233
TI  - Folding of intestinal brush border enzymes. Evidence that high-mannose
      glycosylation is an essential early event.
AB  - A polyvalent antiserum which precipitates the native, folded, but not the
      denatured molecular forms of pig intestinal aminopeptidase N (EC 3.4.11.2) and
      sucrase-isomaltase (EC 3.2.1.48, EC 3.2.1.10) was used to determine the kinetics
      of polypeptide folding of the two newly synthesized brush border enzymes. In
      pulse-labeled mucosal explants, complete synthesis of the polypeptide chains of
      aminopeptidase N and sucrase-isomaltase required about 2 and 4 min, respectively,
      whereas maximal antiserum precipitation was acquired with half-times of 4-5 and 8
      min, respectively. Fructose, which induces a defective cotranslational high
      mannose glycosylation, increased the half-time of polypeptide folding to about 12
      min for aminopeptidase N as well as for sucrase-isomaltase. Short-pulse
      experiments suggested that fructose exerts its effect by slowing the rate of
      glycosylation, making this partially a posttranslational process. In the presence
      of fructose, not only the malglycosylated forms but also the electrophoretically
      normal, high-mannose-glycosylated form of the brush border enzymes were retained
      in the endoplasmic reticulum and proteolytically degraded. The results obtained
      demonstrate an intimate interrelationship between glycosylation and polypeptide
      folding in the synthesis of membrane glycoproteins and, more specifically,
      indicate that the timing of these two early biosynthetic events is essential for
      correct polypeptide folding.

PMID- 1347234
TI  - The role of tryptophan in structural and functional properties of equinatoxin II.
AB  - A pore-forming, cytolytic and lethal polypeptide, equinatoxin II, from the sea
      anemone Actinia equina, was subjected to oxidation with N-bromosuccinimide to
      study the role of five present tryptophan residues in structure-function
      relationships. In the folded toxin molecule, 1-2 tryptophan residues were readily
      susceptible to oxidation with N-bromosuccinimide, whereas modification of a
      single residue resulted in complete impairment of the toxin lethal and hemolytic
      activities as well as the ability of an oxidized toxin to precipitate with serum
      lipoproteins. CD and fluorescence spectra indicated a slight alteration of a
      toxin secondary structure following N-bromosuccinimide treatment. Incubation with
      sphingomyelin of the toxin prior to oxidation did not prevent subsequent
      modification with N-bromosuccinimide and loss of its activities, indicating that
      the modified tryptophan residue is not directly involved in toxin binding and
      insertion into lipid membranes. It was concluded that the modified tryptophan
      residue is essential for the structure of equinatoxin II.

PMID- 1347235
TI  - The role of lysine, histidine and carboxyl residues in biological activity of
      equinatoxin II, a pore forming polypeptide from the sea anemone Actinia equina L.
AB  - Equinatoxin II, a pore forming polypeptide from the sea anemone Actinia equina L.
      was subjected to chemical modifications with group specific reagents. Lysine
      residues were modified with pyridoxal-5'-phosphate, histidine residues with
      diethyl pyrocarbonate and carboxyl groups with the use of a water soluble
      carbodiimide. Modification of charged residues had no significant influence on
      the toxin interaction with serum lipoproteins. Lysine 5'-phosphopyridoxylated and
      histidine carbethoxylated derivatives of the toxin retained lethal and hemolytic
      activities, but the pH profile of hemolytic activity of 5'-phospho
      pyridoxylequinatoxin II was markedly altered. Modification of the toxin carboxyl
      groups impaired both hemolytic and lethal activities, the latter, however, to the
      greater extent.

PMID- 1347236
TI  - Conformational integrity of a recombinant toxoid of Pseudomonas aeruginosa
      exotoxin A containing a deletion of glutamic acid-553.
AB  - A mutant form of Pseudomonas aeruginosa exotoxin A (ETA) carrying a deletion of
      glutamic acid-553, an important active-site residue, was expressed in an ETA
      negative strain of P. aeruginosa and shown to be exported from the cells as
      efficiently as wild-type ETA. The mutant protein, purified from the culture
      medium, was devoid of ADP-ribosyltransferase activity. Protein conformation was
      barely perturbed by the deletion, as determined by a number of measures,
      including affinity for substrate NAD, proteinase sensitivity, absorbance and
      fluorescence spectroscopy, and differential scanning calorimetry. The
      conformational integrity and stability of the mutant toxin are consistent with
      potential use of the protein in vaccines or as a carrier in preparing conjugate
      vaccines.

PMID- 1347237
TI  - Do antiarrhythmic doses of magnesium potentiate vecuronium?
AB  - The purpose of this study was to investigate whether magnesium sulfate (MgSO4) at
      a dose commonly used to treat arrhythmias potentiates vecuronium. After
      Institutional Review Board approval, 20 randomly assigned, consenting patients
      received a bolus of either MgSO4 (30 mg/kg) or placebo in a blinded fashion.
      Immediately after receiving the bolus of either MgSO4 or placebo, the study
      patients were taken to the operating room (OR) and anesthetized. The ED95 of
      vecuronium was determined in both groups by administering 10 micrograms/kg
      boluses of vecuronium until 95% twitch depression was measured. Delay to 25%
      twitch height recovery (indicating that the neuromuscular block could be reversed
      for extubation) was measured in 10 patients. Ultrafilterable magnesium levels
      were measured in a total of 13 patients. Magnesium levels were drawn before the
      magnesium/placebo bolus, 5 minutes after bolus, and 30 minutes after bolus. The
      data did not demonstrate any relationship between the use of MgSO4 at 30 mg/kg
      doses and either the ED95 or the duration of vecuronium. A 30 mg/kg bolus of
      MgSO4 roughly doubled ultrafilterable magnesium levels from baseline. The limited
      sample size precluded making any firm conclusions from this data. The data trend
      suggested that antiarrhythmic doses of MgSO4 may not potentiate vecuronium.

PMID- 1347238
TI  - Morphoregulation.

PMID- 1347239
TI  - The pattern of expression of the chicken homolog of HOX1I in the developing limb
      suggests a possible role in the ectodermal inhibition of chondrogenesis.
AB  - Homeobox-containing genes have been implicated in a variety of patterning events
      during vertebrate limb development. In an attempt to isolate cDNAs corresponding
      to 5' members of the chicken HOX 4 cluster of homeobox-containing genes, a cDNA
      library constructed from mRNAs expressed during early stages of chick limb
      development was screened with probes generated by the polymerase chain reaction
      (PCR) using oligonucleotide primers corresponding to sequences in the homeoboxes
      of the human HOX4C and HOX4F genes, the human homologs of Hox-4.4 and Hox-4.6.
      This screening resulted in the isolation of full length cDNAs for the chicken
      homolog of HOX4F (cognate of mouse Hox-4.6), which we have termed GHox-4.6, and
      the chicken homolog of human HOX1I, which we have named GHox-1i, a paralog of Hox
      4.6 in the HOX 1 cluster. The homeodomains encoded by GHox-4.6 and GHox-1i differ
      by only three amino acids, and the two proteins show extensive similarity along
      their entire lengths. Despite their sequence similarity, in situ hybridization
      analysis has revealed that GHox-4.6 and GHox-1i exhibit strikingly different
      spatial patterns of expression during embryonic chick limb development. At early
      stages of limb development (stages 20-22), GHox-4.6 transcripts are present in
      high amounts throughout the posterior half of the limb mesoderm and are absent
      from the anterior half of the mesoderm, an expression pattern consistent with the
      possible involvement of GHox-4.6 in the specification of posterior positional
      identity. In contrast, GHox-1i exhibits no distinct anterior-posterior polarity
      of expression at stage 22, but rather is expressed in high amounts throughout the
      mesenchyme of the limb bud. At later stages of development (stage 25), GHox-1i
      continues to be expressed in high amounts throughout the undifferentiated
      mesenchyme subjacent to the apical ectodermal ridge, and, in addition, is
      expressed in the mesodermal cells in the proximal peripheral regions of the limb
      bud subjacent to the ectoderm which are differentiating into nonchondrogenic
      lineages. Conversely, little or no expression of GHox-1i is detectable in the
      proximal central core of the limb bud where chondrogenic differentiation is
      occurring. Thus, GHox-1i is expressed by the undifferentiated subridge
      mesenchymal cells and proximal peripheral mesenchymal cells of the limb bud that
      are being inhibited from undergoing chondrogenesis by the apical ectodermal ridge
      and nonridge ectoderm.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1347240
TI  - Tardive dyskinesia and type II schizophrenia.
AB  - Cognitive impairment, negative and positive symptoms, primitive release reflexes,
      and age/temporal disorientation were assessed in 20 male patients meeting the DSM
      III-R criteria for chronic schizophrenia and Schooler & Kane's criteria for TD.
      The control group comprised 20 age-matched male chronic schizophrenic patients
      without TD. Significant associations were found between TD, cognitive impairment,
      some negative symptoms, and formal thought disorder. These associations were
      independent of other illness and treatment variables. The severity of TD
      correlated significantly with that of cognitive impairment.

PMID- 1347241
TI  - Flashbacks following MDMA.

PMID- 1347242
TI  - The antinociceptive activity of excitatory amino acids in the rat brainstem: an
      anatomical and pharmacological analysis.
AB  - Rats were stereotaxically implanted with microinjection cannulae aimed at sites
      ranging caudally from the lower medulla and rostrally to the diencephalon and
      received microinjections of the excitatory amino acid: L-glutamate 30 nmol/0.5
      microliters. The subsequent spontaneous behavioral response and the effect on the
      thermal noxious-evoked tail flick (TF) and hot plate (HP) responses was recorded.
      From 331 brain sites mapped with glutamate, an elevation of tail flick and hot
      plate response latencies was observed in 59 cases and in 34 of these sites the
      antinociceptive activity was preceded by a shortlasting aversion characterized by
      vocalization and running. The glutamate-sensitive sites at which TF and HP
      response latencies were elevated were exclusively distributed in the medullary
      reticular formation (MRF) and the mesencephalic periaqueductal gray matter (PAG).
      The aversive and antinociceptive activity of glutamate was dose-dependent and
      mimicked by the excitatory amino acid (EAA) receptor agonists N-methyl-D
      aspartate + (NMDA) kainate and less so quisqualate. The EAA receptor antagonists
      MK-801 and AP-5, but not glutamyl-amino-methyl-sulfonic acid, antagonized in a
      dose-dependent fashion both the aversive and antinociceptive responses evoked
      from the PAG. It is suggested that NMDA receptor-linked neurons in the PAG
      activate both nociceptive and antinociceptive systems.

PMID- 1347243
TI  - Brain glutamine synthetase increases following cerebral ischemia in the rat.
AB  - Changes in astrocyte glutamine synthetase (GS) in postischemic rat brain were
      evaluated and correlated with regional neuronal vulnerability or resistance to
      ischemia. Rats subjected to 20 or 30 min of cerebral ischemia were allowed to
      survive for 3 or 24 h after ischemia; normal animals served as controls.
      Resultant neuronal necrosis was severe in the striatum by 24 h and in the CA1
      region of the hippocampus at 72 h; neurons in paramedian cortex and CA3 region of
      the hippocampus were not permanently damaged. Glutamine synthetase (GS)
      immunocytochemistry was performed on vibratome sections of paraformaldehyde-fixed
      brains and enzyme activity was assayed in frozen samples of cerebral cortex,
      striatum and hippocampus. At 3 and 24 h after ischemia, GS immunoreactivity
      increased and was secondary to enlargement of GS-positive cell bodies and
      processes as well as to increased numbers of GS-positive astrocytes. Enzyme
      activity also increased in cortex, striatum and hippocampus at 3 and 24 h (P less
      than or equal to 0.03). This study shows that increase in astrocyte GS occurs
      rapidly after ischemia, and prior studies indicate that this increase occurs in
      parallel with proliferative changes in astrocyte organelles. The results also
      suggest that astrocyte metabolism of glutamate increases after ischemia. The
      increased capacity for glutamine synthetase may be important in normalizing
      extracellular glutamate following ischemia and protecting brain from the
      neurotoxic effects of this excitatory amino acid.

PMID- 1347244
TI  - Evoked CA3 field potentials corresponding to both EPSPs and IPSPs in hippocampal
      slice.
AB  - Biphasic field potentials were recorded in the CA3 distal dendritic region in
      response to both antidromic (fornix) and orthodromic (mossy fiber) stimulation in
      guinea pig hippocampal slices in vitro. The positive component (P1) corresponded
      to intracellularly recorded excitatory postsynaptic potentials. The negative
      component (N1) appears to be due to GABAA-mediated inhibitory postsynaptic
      potentials (IPSPs) since it corresponded to the fast IPSP recorded
      intracellularly, was blocked by bicuculline and penicillin and augmented by
      barbiturates. The amplitude of N1 and the duration of P1 are sensitive and useful
      measures of the GABAA-mediated IPSP.

PMID- 1347245
TI  - Glutamate stimulation of tyrosine hydroxylase is mediated by NMDA receptors in
      the rat striatum.
AB  - We have studied the action of glutamate on striatal tyrosine hydroxylase activity
      and determined which type of glutamate receptors are involved. Glutamate
      stimulated (EC50 = 4 +/- 2 microM) the activity of tyrosine hydroxylase in slices
      of rat neostriatum. The selective N-methyl-D-aspartate (NMDA) receptor antagonist
      2-amino-5-phosphonovalerate (10 microM) blocked the stimulation; however, both
      the non-NMDA receptor antagonist glutamate diethyl ester (10 microM) and the
      general excitatory amino acid antagonist kynurenate (10 microM) had no effect.
      NMDA was even more potent than glutamate in stimulating tyrosine hydroxylase
      activity. Quisqualate (100 microM) only slightly stimulated the enzyme, and
      kainate had practically no effect. Omission of Mg2+ from the incubation medium
      potentiated the glutamate stimulation. Neither tetrodotoxin nor atropine
      prevented the stimulation. These results suggest that glutamate stimulates
      striatal tyrosine hydroxylase activity via NMDA receptors. The lack of effect of
      tetrodotoxin and atropine suggests that glutamate acts on NMDA receptors located
      on the dopaminergic nigrostriatal terminal. The stimulation may involve the entry
      of Ca2+ into the terminal through the NMDA receptor ionophore, since a Ca(2+)
      free medium or cadmium totally blocked the stimulation of the enzyme by
      glutamate.

PMID- 1347246
TI  - Age-related changes in the turnover rates of D1-dopamine receptors in the retina
      and in distinct areas of the rat brain.
AB  - The steady-state density and the turnover rates of D1-dopamine receptors were
      investigated in the striatum, nucleus accumbens, substantia nigra, and retina of
      adult (3-month-old) and aged (23-month-old) rats. The turnover rates were
      measured by monitoring the repopulation kinetics of D1-dopamine receptors labeled
      with [3H]-SCH 23390 after the irreversible inactivation induced by a single dose
      of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 mg/kg, s.c.). In all
      the neural tissues examined, the repopulation of D1 dopamine receptors could be
      adequately described by a theoretical model that assumes a constant rate of
      receptor production (i.e. zero order) and a rate of degradation that is dependent
      on the receptor density at any time (i.e. first order). The results obtained
      indicate that the reduction in the density of D1-dopamine receptors in the
      striatum, nucleus accumbens and substantia nigra of aged rats is the result of a
      larger decrease in the receptor production rate (-44 to -60%) than in the
      receptor degradation rate (-21 to -46%). By contrast, the production rate of D1
      dopamine receptors in the retina of aged rats remains unchanged, whilst the
      degradation rate is reduced by 25%. This results in an age-related increase in
      the density of D1-dopamine receptors in the rat retina.

PMID- 1347247
TI  - Lack of serotonin neurotoxicity after intraraphe microinjection of (+)-3,4
      methylenedioxymethamphetamine (MDMA).
AB  - Systemic administration of 3,4-methylenedioxymethamphetamine (MDMA) produces
      depletions of serotonin (5-HT) and its primary metabolite, 5-hydroxyindoleacetic
      acid (5-HIAA), decreases 5-HT reuptake sites and diminishes tryptophan
      hydroxylase activity in various forebrain regions. MDMA has been shown to be
      neurotoxic to the fine fibers originating from dorsal raphe (DR) 5-HT neurons but
      not the beaded fibers from the median raphe (MR) nucleus. In the present
      experiment, MDMA was microinjected directly into the DR or MR to determine
      whether differential neurotoxicity developed in the DR versus MR fiber systems as
      measured by 5-HT levels and immunocytochemistry. Two weeks following stereotaxic
      injection with either vehicle or (+)MDMA (50 micrograms base in 2 microliters)
      into the DR or MR, rat brains were assayed for 5-HT and catecholamine content or
      5-HT immunocytochemistry. HPLC analysis revealed no significant changes in
      monoamine or metabolite concentrations in the hippocampus and striatum of rats
      administered intra-DR or -MR (+)MDMA. Raphe sections stained for 5-HT also did
      not reveal any apparent neurotoxicity. A single cerebral injection of (+)MDMA
      does not produce neurotoxicity to 5-HT neuronal systems originating in the raphe,
      although neurotoxicity of multiple MDMA injections into these raphe nuclei cannot
      be ruled out.

PMID- 1347248
TI  - Evidence for dorsal root projection to somatostatin-immunoreactive structures in
      laminae I-II of the spinal dorsal horn.
AB  - In order to determine if somatostatin (SOM)-immunoreactive (I) cell bodies and
      processes in lamina (L) II of the rat spinal cord receive dorsal root input, the
      latter were anterogradely labeled by wheat germ agglutinin-conjugated horseradish
      peroxidase (WGA-HRP). SOM-I structures were demonstrated by immunohistochemistry.
      Cell bodies labeled transscellularly or transsynaptically by WGA-HRP and
      immunohistochemically for SOM were present in L II. In addition, a L I cell was
      double labeled. These results suggest that some dorsal root axons innervate SOM-I
      neurons in L I-II of the spinal cord. In addition to confirming
      immunohistochemical observations in published reports, we have revealed SOM-I
      central terminals in the type II glomerulus. Further, a SOM-I CI-terminal,
      presumed to be of primary afferent origin, contacted a SOM-I dendrite in L II.
      Since SOM has been implicated in nociceptive function in the dorsal horn, it is
      possible that some of the SOM-I structures identified are involved in nociceptive
      processing.

PMID- 1347250
TI  - American Cancer Society and American Joint Committee on Cancer Workshop on
      Molecular Markers in the Classification and Staging of Cancer, Atlanta, Georgia,
      December 13-14, 1990.

PMID- 1347249
TI  - Pattern of neuronal death in the rat hippocampus after status epilepticus.
      Relationship to calcium binding protein content and ischemic vulnerability.
AB  - The pattern of hippocampal cell death has been studied following hippocampal
      seizure activity and status epilepticus induced by 110-min stimulation of the
      perforant pathway in awake rats. The order of vulnerability of principal cells in
      the different hippocampal subfields--as determined by silver impregnation--was
      found to be very similar to the pattern found in ischemia; i.e., dentate hilus
      greater than CA1, subiculum greater than CA3c greater than CA3a,b greater than
      dentate granule cells. The hilar somatostatin-containing cells were the most
      vulnerable cell type, whereas all other subpopulations of nonprincipal neurons-
      visualized by immunocytochemistry for the calcium binding proteins parvalbumin
      and calbindin--were remarkably resistant. Pyramidal cells in the CA3 region
      containing neither of the examined calcium binding proteins were more resistant
      to overexcitation than CA1 pyramidal cells, most of which do contain calbindin.
      This indicates that no simple relationship exists between vulnerability in status
      epilepticus and neuronal calcium binding protein content, and that local and/or
      systemic hypoxia during status epilepticus may be responsible for the ischemic
      pattern of cell death.

PMID- 1347251
TI  - Protein kinase C isoforms in multidrug resistant P388/ADR cells: a possible role
      in daunorubicin transport.
AB  - To identify the role of protein kinase C (PKC) isoforms in multidrug resistance
      in tumor cells, we examined the PKC isoform pattern in the multidrug resistant
      P388/ADR cell line and studied the effect of down regulation of PKC isoforms on
      intracellular daunorubicin accumulation and P-glycoprotein expression. Using
      monoclonal antibodies to PKC alpha, beta and gamma and flow cytometry technique
      we showed that P388/ADR cells overexpressed PKC alpha and beta as compared to
      drug sensitive P388 cells. Prolonged treatment of P388/ADR cells with phorbol
      myristate acetate (PMA), a procedure that is known to down regulate PKC, resulted
      in the down regulation of total PKC activity and the PKC beta isoform (at the
      protein level) that was accompanied by the correction of daunorubicin
      accumulation in P388/ADR cells. The level of expression of P-glycoprotein in PMA
      treated cells was similar to that of untreated cells. These results suggest that
      PKC beta regulates the drug efflux function of P-glycoprotein.

PMID- 1347252
TI  - p53 mutations in human malignant gliomas: comparison of loss of heterozygosity
      with mutation frequency.
AB  - Mutations in the p53 gene were analyzed in 40 gliomas using the single strand
      conformation polymorphism assay together with restriction fragment length
      polymorphism analysis to assess loss of heterozygosity for 17p alleles in the
      same tumors. Mutations occurred in 40% of the gliomas and were found in exons 4-8
      of the p53 gene. G:C to T:A transversions, which occur in high frequency in some
      lung (greater than 50%), liver (greater than 80%), breast (30%), and esophageal
      cancers (25%), were noted in greater than 25% of the gliomas studied here. These
      transversions were clustered in exon 5 from codons 156 to 168, a region of the
      p53 gene not previously associated with a high frequency of mutation, and may
      represent a new hot spot for mutations in certain cancers. The majority of
      gliomas (27 of 38) analyzed here retained both 17p alleles. The frequency of p53
      mutations was 37% in this group of tumors and increased to 64% in tumors with one
      17p allele. Allelic loss for chromosome 17p occurred in 4 of 11 gliomas
      independently of mutations in the p53 gene. Absence of p53 mutations in 36% of
      the tumors with one 17p allele suggests that a tumor suppressor gene other than
      p53 may be located on chromosome 17p and involved in progression to malignancy of
      some gliomas.

PMID- 1347253
TI  - Different pattern of chromosomal allele loss in multiple hepatocellular
      carcinomas as evidence of their multifocal origin.
AB  - One of the most problematic aspects of surgery for hepatocellular carcinoma (HCC)
      is the frequent development of multiple tumors. Determination of the origin of
      multiple tumors, i.e., multifocal or metastatic, is important for predicting the
      clinical course of the disease after surgery. In order to clarify the origin of
      multiple tumors of HCC genetically, we examined patterns of loss of
      heterozygosity (LOH) on chromosome 16 for DNA isolated from 43 HCCs resected from
      19 patients by analysis of restriction fragment length polymorphism. The cases
      were classified macro- and microscopically into 3 groups: multifocal origin;
      metastatic origin; and undetermined. Classification based on morphological
      features was shown to be well correlated with patterns of LOH in multiple tumors
      of HCC. Different patterns of LOH on chromosome 16 were detected in 8 of 11
      patients with tumors of morphologically multifocal origin, whereas they were
      detected in none of 5 patients with tumors of morphologically metastatic origin.
      Among five patients with tumors of morphologically undetermined origin, a
      difference of LOH pattern among the tumors was detected in two, whereas in the
      other three, the pattern was identical between the tumors. A different pattern of
      LOH among HCCs arising in situ showed that they were composed of different
      clones, strongly suggesting their independent clonal origin and multifocal
      development. These results show that not only appropriate morphological
      observation but also examination of the LOH pattern on a particular chromosome is
      useful in diagnosis of multifocal HCC.

PMID- 1347255
TI  - Proceedings of the Second Joint WHO/ISH Symposium on the Prevention of
      Hypertension and Cardiovascular Disease, Camoglia, Italy, June 1-3, 1991.

PMID- 1347254
TI  - Persistent measles virus infection enhances major histocompatibility complex
      class I expression and immunogenicity of murine neuroblastoma cells.
AB  - The effect of persistent measles virus infection on the expression of major
      histocompatibility complex (MHC) class I antigens was studied. Mouse
      neuroblastoma cells C1300, clone NS20Y, were persistently infected with the
      Edmonston strain of measles virus. The persistently infected cell line, NS20Y/MS,
      expressed augmented levels of both H-2Kk and H-2Dd MHC class I glycoproteins.
      Activation of two interferon(IFN)-induced enzymes, known to be part of the IFN
      system: (2'-5')oligoadenylate synthetase and double-stranded-RNA-activated
      protein kinase, was detected. Measles-virus-infected cells elicited cytotoxic T
      lymphocytes that recognized and lysed virus-infected and uninfected neuroblastoma
      cells in an H-2-restricted fashion. Furthermore, immunization of mice with
      persistently infected cells conferred resistance to tumor growth after challenge
      with the highly malignant NS20Y cells. The rationale for using measles virus for
      immunotherapy is that most patients develop lifelong immunity after recovery or
      vaccination from this infection. Patients developing cancer are likely to have
      memory cells. A secondary response induced by measles-virus-infected cells may
      therefore induce an efficient immune response against non-infected tumour cells.

PMID- 1347256
TI  - Regression of left ventricular hypertrophy--a meta-analysis.
AB  - Left ventricular hypertrophy (LVH) is an independent risk indicator of
      cardiovascular disease. Obtaining reversal of hypertension-induced cardiac
      hypertrophy seems to be a desirable objective of antihypertensive treatment. A
      total of 2,357 patients were included in a meta-analysis on the effect of
      antihypertensive pharmacological therapy on LVH. Overall left ventricular mass
      (LVM) was reduced by 11.9% (95% confidence interval (CI) 10.1-13.7) in parallel
      with a reduction of mean arterial pressure of 14.9% (CI 14.0 to 15.8). When
      evaluating the effect of first-line therapies on calculated LVM using the same
      formula for all studies, the absolute reductions in g were 44.7 (ACE-inhibitors),
      22.8 (beta-blockers), 26.9 (calcium antagonists) and 21.4 (diuretics) when
      adjusted for differences between studies (ANCOVA). It can be concluded that
      effective antihypertensive therapy reduces LVM. ACE-inhibitors, beta-blockers and
      calcium antagonists reduce LVM by reducing wall hypertrophy, the effect of ACE
      inhibitors being the most pronounced. Diuretics reduce LVM mainly through an
      effect on left ventricular inner diameter. How these effects affect prognosis is
      still an open question.

PMID- 1347257
TI  - The secondary prevention of myocardial infarction by drug treatment; excluding
      lipid lowering agents.
AB  - About 10% of survivors of an acute myocardial infarction will die in the
      following year. Thereafter the risk declines but reinfarction is still an
      important cause of mortality and morbidity. The post infarction trials have
      clearly shown that the best proven agents to mitigate this toll are aspirin, beta
      adrenoceptor blockers, and verapamil (but not other calcium blockers, except
      diltiazem for non Q wave infarction). In the context of hypertension treatment
      these post infarction trials may have important lessons for drug selection and
      ancillary treatment since the majority of subjects will ultimately die of
      ischaemic heart disease. Although the newer agents such as ACE and renin
      inhibitors, newer calcium channel blockers and alpha blockers have many promising
      properties in terms of risk factor reduction, no convincing mortality data
      exists; it is needed. This review will deal with the known effects (both good and
      bad) of antihypertensive agents and will also review other drug strategies
      relevant to the hypertensive patient. It will also point out large areas of
      ignorance.

PMID- 1347258
TI  - An evaluation of the safety of the beta-modulator cicloprolol in chronic heart
      failure.
AB  - The new beta-adrenoceptor partial agonist cicloprolol acts as a beta-agonist at
      normal levels and as a beta-antagonist at high levels of adrenergic discharge.
      Treatment with cicloprolol should protect the heart against excessive
      stimulation, while providing a baseline level of sympathetic drive. The clinical
      interest of such a profile is, however, not yet established in heart failure.
      Accordingly this study examined the safety of oral cicloprolol, a step necessary
      before undertaking efficacy comparison with other compounds recently proposed to
      treat heart failure. Twenty-five patients were studied. Cicloprolol was given
      once a day for 2 weeks in a crossover double-blind placebo-controlled design.
      Follow-ups were obtained at baseline and at the end of each period. At baseline
      all patients had clear evidence of heart failure. Cicloprolol did not affect
      resting heart rate and blood pressure, but it reduced significantly peak exercise
      heart rate and peak rate-pressure product. The effect was especially significant
      in patients with sinus rhythm. The drug did not induce bradycardia or
      arrhythmias. Resting and exercise ejection rate were not affected. Cicloprolol
      improved the quality of life and the work capacity of 5 of 12 patients with
      congestive failure due to ischemic etiology. Side effects were few and similar
      with placebo and cicloprolol. Thus, short-term administration of cicloprolol is
      safe in moderate heart failure.

PMID- 1347259
TI  - Responsiveness of superficial hand veins to alpha-adrenoceptor agonists in
      insulin-dependent diabetic patients.
AB  - 1. Diabetic autonomic neuropathy causes loss of sympathetic cardiovascular
      control and is associated with increased vascular sensitivity to catecholamines.
      Supersensitivity to catecholamines could be due to either a postsynaptic increase
      in vascular sensitivity or to decreased catecholamine uptake into peripheral
      sympathetic nerve endings. 2. To differentiate between these possible mechanisms
      we have measured the responsiveness in vivo to noradrenaline and phenylephrine
      with local infusions into peripheral veins of diabetic patients with and without
      symptomatic autonomic neuropathy and of healthy control subjects. The dorsal hand
      vein compliance technique was used. 3. Symptomatic diabetic patients required
      significantly lower doses of noradrenaline for half-maximal venoconstriction
      (ED50) (geometric mean 2.14 ng/min) than control subjects (geometric mean 6.61
      ng/min, P = 0.032), but there was no difference in the results from the
      phenylephrine dose-response curves between the groups. There were no differences
      in venous responsiveness to noradrenaline or phenylephrine between the
      asymptomatic diabetic group and the control group. However, in the asymptomatic
      diabetic group, postural blood pressure change (an index of loss of sympathetic
      control) was correlated with the ED50 for noradrenaline (r = 0.74, P = 0.014),
      but not with the ED50 for phenylephrine. In the control group the ED50 values for
      noradrenaline and phenylephrine were correlated with each other (r = 0.81, P =
      0.0005). 4. Both vasopressor drugs act on vascular alpha-adrenoceptors, but only
      noradrenaline is taken up into peripheral sympathetic nerve endings. Our results
      suggest that, in diabetic patients, vascular supersensitivity to catecholamines
      is primarily determined by decreased neuronal catecholamine uptake. A
      postsynaptic increase in vascular alpha-adrenoceptor stimulation does not appear
      to be prominent in diabetic autonomic neuropathy.

PMID- 1347260
TI  - Formation of prostacyclin during administration of beta 1-selective and non
      selective beta-adrenergic antagonists in healthy humans.
AB  - Vascular formation of prostacyclin is increased by propranolol in patients with
      essential hypertension. However, the possible effect of beta-adrenoceptor
      blocking drugs in healthy subjects is, however, not known. We studied this issue
      by analysis of the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6
      keto-prostaglandin F1a during intake of a beta 1-selective (metoprolol) or a non
      selective (propranolol) beta-adrenoceptor antagonist. After 14 days of metoprolol
      treatment (100 mg d-1) the urinary excretion of PGI-M did not differ from control
      (253 +/- 77 vs. 220 +/- 33 pg mg-1 creatinine, respectively). Five days of
      randomized cross-over treatment with propranolol (80 mg day-1) or placebo did not
      affect urinary PGI-M significantly either (177 +/- 11 vs. 202 +/- 11 pg mg-1
      creatinine, respectively). Furthermore, a daily increasing dose of propranolol
      (80-480 mg) progressively lowered resting blood pressure and heart rate, but
      failed to influence urinary excretion of PGI-M. The data demonstrate that
      metoprolol and propranolol do not affect basal cardiovascular formation of
      prostacyclin in healthy subjects. Thus, the biosynthesis of prostacyclin does not
      appear to be regulated by beta-adrenoceptor activity under normal conditions.

PMID- 1347261
TI  - Fulminant peptic ulcer disease in cardiac surgical patients: pathogenesis,
      prevention, and management.
AB  - OBJECTIVES: To identify pathogenetic factors associated with the development of
      peptic ulcers in patients following cardiac surgery and to examine the efficacy
      of medical and surgical therapy of peptic ulcers in this setting. DESIGN:
      Retrospective study with randomly selected case controls. SETTING: University
      hospital referral practice. PATIENTS: A total of 9,199 consecutive patients
      undergoing procedures requiring cardiopulmonary bypass between January 1, 1980
      through September 30, 1988, were reviewed. Life-threatening ulcer complications
      were defined as hemorrhage of greater than 2 units of packed red blood cells
      which prompted subspecialty consultation and required a therapeutic intervention.
      Patients who developed life-threatening complications of peptic ulcers (32/9199,
      0.35%) (group 1) were compared with 32 randomly selected patients (group 2) for
      differences in potential pathogenetic factors and outcome. MAIN OUTCOME MEASURES:
      Gastrointestinal hemorrhage, perforated ulcers, death. RESULTS: Patients in group
      1 were significantly older than patients in group 2 (66.7 +/- 7.9 vs. 54 +/- 10
      yrs, p less than .01). Complications following cardiopulmonary bypass requiring
      further surgery or causing prolonged hypotension were significantly more frequent
      in patients with ulcers than in controls (10/32 vs. 1/32, p less than .005). The
      mortality rate for patients in group 1 was 34.3% (11/32) compared with 0% in
      group 2 (p less than .001). Perioperative ulcer prophylaxis was employed with
      equal frequency in groups 1 and 2 and did not correlate with outcome.
      CONCLUSIONS: The development of complications of postoperative peptic ulcers
      following cardiac surgery correlates with age, need for reoperation, and
      hypoperfusion, but not with the use of prophylactic regimens to suppress acid
      secretion. These results suggest that impairment of gastric and duodenal mucosal
      defense mechanisms is a critical factor in the development of postoperative
      peptic ulcers.

PMID- 1347262
TI  - A model for conversion from small volume nebulizer to metered dose inhaler
      aerosol therapy.
AB  - Rationing of medical services will be necessary if we do not develop a more
      rational and efficient health care system. Respiratory care services are
      receiving emphasis as we try to curtail spiraling health care costs. In analysis
      of our respiratory care services, we found that small volume nebulizer (SVN)
      therapy was still a major portion of our workload. We instituted a protocol to
      convert to metered dose inhaler (MDI) therapy. All hospitalized patients,
      excluding those admitted to the spinal cord unit and intensive care units, with a
      physician's order for aerosol delivery by SVN, were evaluated by respiratory care
      practitioners for conversion to MDI therapy. A simple protocol for the therapist
      to use in this conversion was developed. All patients converted to MDI were
      trained in appropriate MDI use by the therapist. A three-day follow-up of each
      patient's compliance with proper MDI therapy was initiated. Even with a 72-h
      allowance for initial SVN treatment, we realized a 9,350 procedure reduction from
      deleted treatments and an additional 7,650 conversions to MDI. Less than 2
      percent of our patients failed to make a completely successful conversion to MDI.
      Those patients who successfully converted to MDI resulted in reduced hospital
      costs of $43,758 based on excess medication, supplies, and labor costs associated
      with SVN treatments. We also saved 5,000 h of technician time that was used to
      further instruct patients in appropriate MDI therapy. Aerosol therapy by MDI is
      cost-effective therapy. The institution of guidelines for MDI conversion has
      reduced fear of failure for both clinicians and patients and illustrates the
      importance of patient education by qualified respiratory therapists.

PMID- 1347263
TI  - 34th annual Thomas L. Petty Aspen Lung Conference: Epithelial Cell Biology and
      Airway Disease.

PMID- 1347264
TI  - Neutrophil adhesion to parainfluenza virus-infected human airway epithelial
      cells. Possible contributions of ICAM-1-dependent and ICAM-1-independent
      mechanisms.

PMID- 1347265
TI  - [Clinical aspects, diagnosis and surgical therapy of persistent primary
      hyperparathyroidism].
AB  - Between January 1991 and September 1991 424 patients were operated on for
      hyperparathyroidism (HPT) at the Department of Surgery, University of Heidelberg.
      In 8.5% of cases a persistent HPT was present. Our own rate of persistence was
      5.4%. Ultrasound revealed the pathology in 44.2% while highly selective venous
      catheterization identified the correct side in 63.4%. 70% of all patients with
      persistent HPT required one operative revision, the remaining 30% having up to 3
      revisions. 27 patients (75%) were operated on successfully. In 12 of these
      patients an ectopic adenoma was found. The adenoma was not identified
      intraoperatively in 2 patients (6.9%). One patient sustained permanent damage to
      the recurrent laryngeal nerve.

PMID- 1347266
TI  - Amylin/IAPP research in Japan. Proceedings of the Amylin/IAPP Symposium,
      Wakayama, Japan, May 10th, 1991.

PMID- 1347267
TI  - Placebo controlled comparison of acute effects of ebastine and clemastine on
      performance and EEG.
AB  - The effects of single oral doses of 10 and 20 mg ebastine were compared with
      placebo and 2 mg clemastine in a double-blind cross-over study in 16 healthy male
      volunteers. Clemastine produced the known pattern of changes, namely impairment
      of psychomotor performance, drowsiness, and a selective effect on cognitive
      processes. Earlier encoding in a perceptual stage was slowed whereas abstract
      classification processes were not affected. Electrophysiological measures of
      vigilance showed a general decrease in vigilance especially 2.5 and 4.5 h after
      dosing. In contrast at no time was any effect of ebastine different from that of
      the placebo. Ebastine 10 and 20 mg differed positively from clemastine in its
      effect on pursuit tracking, subjective rating of drowsiness and general
      discomfort. Ebastine 10 mg also differed positively from clemastine in the EEG
      features of vigilance. It is concluded that 10 and 20 mg ebastine were free from
      sedative adverse effects.

PMID- 1347268
TI  - Characterization of the dopamine receptor expressed by rat glomerular mesangial
      cells in culture.
AB  - Incubation of cultured rat glomerular mesangial cells with dopamine caused an
      increase in cyclic AMP formation in a concentration-dependent manner (Ka apparent
      2.2 microM). The selective dopamine D1 receptor agonists, fenoldopam, SKF 38393
      and (+/-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (6,7-ADTN) also
      produced concentration-dependent increases in cyclic AMP with mean Ka apparent
      values of 0.04 microM, 0.02 microM and 1.02 microM, respectively. Although
      fenoldopam and SKF 38393 were more potent than dopamine, they were partial
      agonists with efficacies, relative to dopamine, of approximately 60 and 35%,
      respectively. The dopamine analogue, 6,7-ADTN, in contrast, behaved as a full
      agonist. Dopamine-stimulated cAMP formation was inhibited in a concentration
      dependent manner by the D1-selective antagonist, SCH 23390, with a Ki of 0.06 nM.
      In contrast, the D2-selective antagonist, domperidone, was four orders of
      magnitude less potent than SCH 23390, having a Ki of 2072 nM. In addition, SCH
      23388, the stereoisomer of SCH 23390, was observed to be two orders of magnitude
      less potent than SCH 23390, indicating the stereoselective nature of the
      receptor. The potency series for the selective agonists and antagonists is the
      same as that described, using identical experimental conditions, for the D1
      receptor expressed by a cell line of central origin confirming that the
      peripheral DA1 and the central D1 dopamine receptor are pharmacologically
      similar.

PMID- 1347269
TI  - Frog cones as well as Muller cells have peroxisomes.
AB  - We have localized D-amino acid oxidase in peroxisomes of frog retina using cerium
      procedures on tissue fixed in mixtures containing lower concentrations of
      glutaraldehyde than we had previously used in our cytochemical studies of this
      enzyme. We find the Muller cells of these preparations contain a more striking
      population of peroxisomes than had previously been thought: the D-amino acid
      oxidase-containing bodies are especially concentrated near the outer limiting
      membrane, but appreciable numbers are also found in the outer plexiform layer and
      near the inner limiting membrane. In addition, we find peroxisomes to be present
      in frog cone photoreceptors, particularly in zones near the ellipsoid. To our
      knowledge peroxisomes have not been described hitherto in vertebrate
      photoreceptors. Possible roles for the peroxisomes of the neural retina include
      participation in the metabolism of lipids (e.g. those of the cones' oil droplets,
      or of the outer segment) and involvement in oxidation of transmitter-related
      amino acids and of other small molecules.

PMID- 1347270
TI  - Evidence for a protective action of the vigilance promoting drug modafinil on the
      MPTP-induced degeneration of the nigrostriatal dopamine neurons in the black
      mouse: an immunocytochemical and biochemical analysis.
AB  - Based on the observations that the psychostimulant drug amphetamine in
      combination with physiotherapy can promote recovery of brain function after brain
      injury, we have studied the ability of the vigilance promoting drug Modafinil to
      counteract 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-(MPTP)-induced
      degeneration of the nigrostriatal dopamine (DA) neurons of the black mouse. MPTP
      was given s.c. in a dose of 40 mg/kg and the mice were sacrificed 2 weeks later.
      The effects of acute and chronic treatment with Modafinil were studied on MPTP
      induced DA neurotoxicity. The substantia nigra and neostriatum were taken to both
      biochemical and histochemical analysis of presynaptic parameters of the
      nigrostriatal DA neurons, the latter in combination with image analysis. In
      separate experiments in rats in vivo tests for DA uptake blocking activity were
      made using intrastriatal microdialysis to study superfusate levels of DA and its
      metabolites and the 4-alpha-dimethylmetatyramine (H77/77) model to test for a
      possible ability of Modafinil to protect against H77/77-induced depletion of
      forebrain DA stores. Chronic treatment with Modafinil in doses of 10 to 100 mg/kg
      counteracted the MPTP-induced disappearance of nigral TH IR nerve cell body
      profiles and neostriatal TH IR nerve terminal profiles as evaluated after 2 weeks
      with image analysis. Chronic treatment with Modafinil (10-100 mg/kg) also dose
      dependently counteracted the MPTP-induced disappearance of striatal DA uptake
      binding sites as evaluated at the same time interval. Also in the dose range 10
      100 mg/kg Modafinil counteracts the MPTP-induced depletion of DA stores both in
      the neostriatum and the substantia nigra. In the acute experiments Modafinil (30
      mg/kg) protected against the MPTP-induced depletion of striatal DA,
      dihydrophenylacetic acid (DOPAC) and homovanillic acid (HVA) levels both when
      given 15 min before, at the same time and 3 h following the MPTP injection. In
      the substantia nigra, however, these protective actions of Modafinil were only
      observed when the drug was coadministered with MPTP. Experiments with
      microdialysis in intact rats failed to demonstrate any increases of superfusate
      DA levels in neostriatum with 30 mg/kg of Modafinil. Modafinil in high doses of 2
      x 50 mg/kg, however, significantly counteracted the H77/77 induced DA depletion
      of striatal DA stores. Thus, morphological and biochemical evidence has been
      obtained that Modafinil in the dose range 10-100 mg/kg protects against MPTP
      induced degeneration of the nigrostriatal DA neurons of the black mouse.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1347271
TI  - Medial vestibular nucleus in the guinea-pig: NMDA-induced oscillations.
AB  - We have recently shown in vivo that N-Methyl-D-Aspartate (NMDA) receptors are
      present in the guinea-pig vestibular complex and demonstrated that they are
      involved in the regulation of the resting discharge of vestibular neurones. A
      parallel in vitro study has identified in the guinea-pig medial vestibular nuclei
      (MVN) two main neuronal cell types, A and B MVNn, differing by their intrinsic
      membrane properties. One subtype of B MVNn was further characterized by the
      presence of a low threshold calcium spike (LTS). The present study investigated
      in vitro the responses of these different cell types to NMDA. Both A and B MVNn
      were depolarized by NMDA, which also induced a decrease in membrane resistance
      and an increase in the spontaneous firing rate. These effects could be blocked by
      D-AP5, a specific antagonist of NMDA receptors. Following a 10-30 mV
      hyperpolarization, a long-lasting oscillatory behavior could be induced in
      presence of NMDA. These oscillations were however restricted to the subtype of B
      MVNn without LTS. The NMDA-induced oscillations were tetrodotoxine-resistant, but
      could be eliminated by D-AP5 or by replacing sodium with choline. Functional
      implications of this oscillatory behavior are discussed.

PMID- 1347272
TI  - Receptor subtypes involved in callosally-induced postsynaptic potentials in rat
      frontal agranular cortex in vitro.
AB  - A slice preparation of rat frontal agranular cortex preserving commissural inputs
      has been used for intracellular recording from layer V pyramidal cells, in order
      to characterize the synaptic potentials induced by stimulation of the corpus
      callosum and to reveal the subtypes of amino acid receptors involved. Stimulation
      of the corpus callosum induced EPSPs followed by early IPSPs with a peak latency
      of 30 +/- 2 ms and late IPSPs with a peak latency of 185 +/- 18 ms. Reversal
      potentials for early and late IPSPs were -75 +/- 5 mV (early) and -96 +/- 5 mV
      (late). Late IPSPs were more dependent on extracellular K+ concentration. The
      early IPSPs were blocked by GABAA antagonists, bicuculline and picrotoxin,
      whereas the late IPSPs were reduced by the GABAB antagonist, phaclofen. CNQX (6
      cyano-7-nitroquinoxaline-2,3-dione), an antagonist of non-NMDA (N-methyl-D
      aspartate) receptors, suppressed both EPSPs and late IPSPs at 5 microM. Early
      IPSPs remained at this concentration but were suppressed by 20 microM CNQX. In
      Mg(2+)-free solution, EPSPs were larger and more prolonged than in control
      solution. These enhanced EPSPs persisted after 5 to 20 microM CNQX, but were
      reduced in amplitude, and their onset was delayed by 3.6 +/- 0.8 ms. The
      remaining EPSPs were suppressed by 50 microM APV (DL-2-amino-5-phosphono-valeric
      acid), an antagonist of NMDA receptors. In Mg(2+)-free solution containing 5 to
      20 microM CNQX, the late IPSPs were not diminished. The remaining late IPSPs were
      suppressed by APV or by phaclofen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347273
TI  - [Electrophysiological studies on the hypothalamic GnRH pulse generator].
AB  - Gonadal function in mammals depends on gonadotropins secreted from the pituitary
      gland in a pulsatile manner. This pulsatility is governed by the periodic
      activation of the hypothalamic GnRH pulse generator. By means of multiple unit
      activity (MUA) recording techniques, characteristics increases in the neuronal
      activity, each of which is associated with the initiation of pulsatile LH
      secretion, have been recorded in the medial basal hypothalamus of the monkey, rat
      and goat. An unambiguous unitary relationship between the increased electrical
      activity (volley) and the LH pulse under a variety of physiological and
      experimental conditions indicates that the MUA volleys represent the electrical
      activity of the GnRH pulse generator. Hypothalamic MUA recordings provide direct
      access to the central component of the neuroendocrine control system which
      governs reproductive function.

PMID- 1347274
TI  - [Relationship between types of hypertension and patterns of urinary catecholamine
      excretion in Sipple's syndrome].
AB  - We report here a case of Sipple's syndrome, and we also analyze the relationship
      between the type of hypertension and urinary excretion of catecholamines in
      Sipple's syndrome based on the literature in Japan. One hundred and fourteen
      cases of Sipple's syndrome have been reported in Japan. The hypertension of
      patients with Sipple's syndrome shows a ratio of fitfull hypertension to
      continual hypertension of 6 to 1, whereas the ratio is 1 to 1.5 in patients whose
      pheochromocytoma is not accompanied by Sipple's syndrome. The patients with
      Sipple's syndrome, being pheochromocytoma can be classified into the adrenaline
      (U-AD) dominant type and noradrenaline (U-NA) dominant type based on the
      catecholamine excretion in the urine. The U-AD predominant (U-AD/U-NA greater
      than 0.4) patients mostly reveal fitfull hypertension, while patients with
      continual hypertension hardly show U-AD predominant.

PMID- 1347275
TI  - Isolation and characterization of genes encoding chaperonin 60 beta from
      Arabidopsis thaliana.
AB  - Chaperonins (Cpn) are implicated in the folding and assembly of multimeric
      proteins in plastids and mitochondria of eukaryotes and in prokaryotes. Plastid
      Cpn is composed of two different polypeptides termed Cpn60 alpha and Cpn60 beta.
      We have isolated cDNA and genomic clones encoding Cpn60 beta from Arabidopsis
      thaliana. The steady-state level of the cpn60 beta mRNAs is higher in etiolated
      leaves and sucrose-treated plants as compared to control leaves. The A. thaliana
      cpn60 beta gene family consists of at least three different coding units. It was
      confirmed that Cpn beta-encoding genes have a high level of conservation among
      plants.

PMID- 1347276
TI  - Highly inducible synthesis of heterologous proteins in epithelial cells carrying
      a glucocorticoid-responsive vector.
AB  - A glucocorticoid-responsive vector is described which allows for the highly
      inducible expression of complementary DNAs (cDNAs) in stably transfected
      mammalian cell lines. This vector, pLK-neo, composed of a variant mouse mammary
      tumor virus long terminal repeat promoter, containing a hormone regulatory
      element, a Geneticin resistance-encoding gene in a simian virus 40 transcription
      unit, and a polylinker insertion site for heterologous cDNAs, was used to express
      the polymeric immunoglobulin (poly-Ig) receptor and the thymocyte marker, Thy-1,
      in Madin-Darby canine kidney (MDCK) cells and in murine fibroblast L cells. A
      high level of poly-Ig receptor or Thy-1 mRNA accumulation was observed in MDCK
      cells in response to dexamethasone with a parallel ten- to 200-fold increase in
      protein synthesis depending on the recombinant protein and the transfected cell
      clone.

PMID- 1347277
TI  - Primary structure of the Aequorea victoria green-fluorescent protein.
AB  - Many cnidarians utilize green-fluorescent proteins (GFPs) as energy-transfer
      acceptors in bioluminescence. GFPs fluoresce in vivo upon receiving energy from
      either a luciferase-oxyluciferin excited-state complex or a Ca(2+)-activated
      phosphoprotein. These highly fluorescent proteins are unique due to the chemical
      nature of their chromophore, which is comprised of modified amino acid (aa)
      residues within the polypeptide. This report describes the cloning and sequencing
      of both cDNA and genomic clones of GFP from the cnidarian, Aequorea victoria. The
      gfp10 cDNA encodes a 238-aa-residue polypeptide with a calculated Mr of 26,888.
      Comparison of A. victoria GFP genomic clones shows three different restriction
      enzyme patterns which suggests that at least three different genes are present in
      the A. victoria population at Friday Harbor, Washington. The gfp gene encoded by
      the lambda GFP2 genomic clone is comprised of at least three exons spread over
      2.6 kb. The nucleotide sequences of the cDNA and the gene will aid in the
      elucidation of structure-function relationships in this unique class of proteins.

PMID- 1347278
TI  - Bismuth subsalicylate in the treatment of H2 blocker resistant duodenal ulcers:
      role of Helicobacter pylori.
AB  - Fifty nine patients with Helicobacter pylori positive duodenal ulcers that failed
      to heal after a six week course of treatment with H2 blockers were randomly
      assigned to one of the following three regimens: (i) bismuth subsalicylate, 600
      mg three times daily (n = 19), (ii) ranitidine, 300 mg at night (n = 20), (iii)
      bismuth subsalicylate plus ranitidine (n = 20). Cumulative ulcer healing rates
      after four and eight weeks respectively were as follows: bismuth subsalicylate
      74% (14/19) and 95% (18/19), ranitidine 40% (8/20) and 65% (13/20), bismuth
      subsalicylate plus ranitidine 80% (16/20) and 95% (19/20). Bismuth subsalicylate
      treatment was better than ranitidine at both four and at eight weeks (p less than
      0.05). The clearance rates for H pylori after four weeks were: bismuth
      subsubsalicylate 58%, ranitidine 0%, bismuth subsalicylate plus ranitidine 55%.
      After stopping bismuth therapy bacterial recrudescence frequently occurred. After
      bismuth treatment 86% (19/22) of ulcers had healed if H pylori had been cleared,
      whereas only 65% (11/17) had healed if H pylori persisted (NS). This study shows
      that bismuth subsalicylate is more effective in the treatment of resistant
      duodenal ulcers than standard dose ranitidine. It may be that suppression of H
      pylori by bismuth subsalicylate promotes ulcer healing.

PMID- 1347279
TI  - Dietary modulation of gluten sensitivity in a naturally occurring enteropathy of
      Irish setter dogs.
AB  - Gluten sensitivity in a naturally occurring enteropathy of Irish setter dogs, and
      the effects of excluding dietary cereal from birth on the subsequent response to
      gluten challenge were investigated. Peroral jejunal biopsy specimens were
      obtained at 1 year of age for morphometric and biochemical examinations, and
      intestinal permeability was assessed using 51Cr-ethylenediaminetetraacetic acid.
      Affected setters, reared on a normal wheat containing diet, exhibited partial
      villus atrophy, intraepithelial lymphocyte infiltration, reduced brush border
      alkaline phosphatase activity, and increased intestinal permeability. Gluten
      sensitivity was shown by introduction of a gluten free diet, which resulted in
      resolution of morphological and biochemical abnormalities and decreased
      intestinal permeability, and subsequent gluten challenge, which resulted in
      relapse. In contrast, littermates reared exclusively on a cereal free diet showed
      minimal changes when challenged with gluten, apart from intraepithelial
      lymphocyte infiltration. These findings document a gluten sensitive enteropathy
      in Irish setters and indicate that exclusion of dietary cereal from birth may
      modify subsequent expression of the disease.

PMID- 1347280
TI  - Prophylactic effects of olsalazine v sulphasalazine during 12 months maintenance
      treatment of ulcerative colitis. The Danish Olsalazine Study Group.
AB  - In a Danish multicentre trial we compared the relapse preventing effects of
      olsalazine and sulphasalazine in patients with ulcerative colitis over a 12 month
      treatment period. Two hundred and twenty seven patients (118 men) with at least
      two previous attacks of ulcerative colitis were randomly allocated according to a
      prearranged treatment schedule to olsalazine 500 mg bd or sulphasalazine 1 g bd
      in a double blind, double dummy fashion. One hundred and ninety seven patients
      completed the trial. The relapse rate after 12 month in the olsalazine group was
      46.9% v 42.4% in the sulphasalazine group with a 95% confidence interval for the
      difference in proportions of -9% to 18%. Seven per cent of the patients were
      withdrawn from the trial because of adverse drug reactions and these were equally
      distributed between the two groups.

PMID- 1347281
TI  - Is the intercellular adhesion molecule-1/leukocyte function associated antigen 1
      pathway of leukocyte adhesion involved in the tissue damage of alcoholic
      hepatitis?
AB  - Alcoholic hepatitis is characterised histologically by an intense inflammatory
      cell infiltrate made up predominantly of neutrophils but including other cell
      types, particularly lymphocytes. Leukocyte cytotoxicity requires cell adhesion,
      which is mediated via receptors on the leukocyte surface including leukocyte
      function associated antigen-1 (LFA-1) which binds to the ligand intercellular
      adhesion molecule-1 (ICAM-1) on the target cell. The distribution of ICAM-1 and
      LFA-1 expression in liver biopsy specimens from patients with alcoholic liver
      disease was examined to ascertain whether this pathway of leukocyte adhesion is
      involved in the tissue damage of alcoholic hepatitis. Specimens were stained for
      ICAM-1 and LFA-1 by a three step immunoalkaline-phosphatase method using
      monoclonal antibodies against ICAM-1 and LFA-1. LFA-1 staining on portal tract
      inflammatory cells and parenchymal inflammatory cells and ICAM-1 staining on
      liver components were examined. ICAM-1 expression on hepatocytes was
      significantly greater in alcoholic hepatitis compared with fatty liver (p less
      than 0.001) and normal controls (p less than 0.01). ICAM-1 expression correlated
      with the histological degree of hepatocellular damage (tau = 0.79; p = 0.0005)
      and parenchymal inflammation (tau = 0.65; p less than 0.001, and with LFA-1
      expression on parenchymal leukocytes (tau = 0.63; p = 0.01). The ICAM-1/LFA-1
      pathway may therefore be involved in leukocyte mediated tissue damage during
      alcoholic hepatitis.

PMID- 1347282
TI  - NEU protein overexpression in benign, borderline, and malignant ovarian
      neoplasms.
AB  - In situ hybridization (ISH) analysis of 24 benign, borderline, and malignant
      ovarian tumor specimens revealed NEU transcript expression by epithelial elements
      in approximately two-thirds of the samples and high-level expression in 3 grade 3
      adenocarcinomas. Immunohistochemical staining (IHC) of a total of 86 specimens
      (including 17 of those studied by ISH) localized NEU antigen expression to
      epithelial cells in 36 of 86 samples with strong membrane staining observed in
      12, including 1 benign, 1 borderline serous carcinoma, 3 clear cell/endometrioid
      carcinomas, and 7 predominantly papillary serous carcinomas with areas of clear
      cell/endometrioid histology. Clinical correlation of the IHC results for the 72
      Stage I-IV invasively malignant neoplasms revealed no statistically significant
      association of the intensity of NEU IHC staining with either relapse-free or
      overall survival. However, more of the patients whose tumors showed strong
      membrane staining for NEU antigen suffered relapses of disease by 3 and 4 years
      than did patients whose tumors showed weak or no membrane staining. These results
      suggest a role for the NEU gene product in the physiology of benign ovarian
      surface epithelium and the neoplastic epithelium of preinvasive borderline and
      some invasively malignant adenocarcinomas.

PMID- 1347284
TI  - Chromosomal mapping of the high affinity Fc gamma receptor gene.

PMID- 1347283
TI  - Polymorphism in a T-cell receptor variable gene is associated with susceptibility
      to a juvenile rheumatoid arthritis subset.
AB  - This report demonstrates a T-cell receptor (Tcr) restriction fragment length
      polymorphism, defined by a Tcrb-V6.1 gene probe and Bgl II restriction enzyme, to
      be absolutely correlated with allelic variation in the coding sequence of a Tcrb
      V6.1 gene. A pair of non-conservative amino acid substitutions distinguish the
      Tcrb-V6.1 allelic variants. An association of this Tcrb-V6.1 gene allelic variant
      with one form of juvenile rheumatoid arthritis (JRA) was established in a cohort
      of 126 patients. The association was observed in patients possessing the HLA
      DQA1*0101 gene. Among HLA-DQA*0101 individuals, 19 of 26 patients (73.1%) carried
      one particular Tcrb-V6.1 gene allele as opposed to 11 of 33 controls (33%; p less
      than 0.005). Haplotypes carrying this HLA gene have previously been shown to
      confer increased risk for progression of arthritis in JRA. This demonstration of
      a disease-associated Tcrb-V gene allelic variant has not, to our knowledge, been
      previously reported and supports the contribution of polymorphism in the Tcr
      variable region genomic repertoire to human autoimmune disease.

PMID- 1347285
TI  - Conservation of an Actinomyces viscosus T14V type 1 fimbrial subunit homolog
      among divergent groups of Actinomyces spp.
AB  - The type 1 fimbrial subunit gene of the human Actinomyces viscosus T14V was used
      as a DNA probe in Southern analyses to detect related DNA sequences in 16 of 30
      strains of Actinomyces spp. under conditions of high stringency. The organisms
      with homology to the DNA probe included two human and six nonhuman A. viscosus,
      three human and three nonhuman A. naeslundii, and two A. bovis isolates.
      Homologous DNA sequences were not detected in strains of A. odontolyticus and A.
      israelii examined in this study. Northern (RNA) blot analysis revealed expression
      of a transcript from each of the A. viscosus and A. naeslundii strains and from
      one A. bovis strain that was comparable in size to that detected from A. viscosus
      T14V. Cell surface fimbriae were observed on a majority of the strains that
      expressed the transcript. Various degrees of cross-immunoreactivities between
      these strains and antibodies specific for type 1 fimbriae of A. viscosus T14V
      were also observed by colony immunoassay. Thus, the data clearly demonstrate the
      existence in, and expression by, divergent Actinomyces groups of genomic
      sequences that are closely related to the type 1 fimbriae of A. viscosus T14V.

PMID- 1347286
TI  - Isolation and characterization of Actinomyces viscosus mutants defective in
      binding salivary proline-rich proteins.
AB  - Recent studies have provided evidence for human salivary proline-rich proteins
      (PRPs) serving as potential receptors in the acquired pellicle for Actinomyces
      viscosus type 1 fimbriae. We report here the isolation of mutants derived from A.
      viscosus T14V-J1 which are defective in binding to PRPs partially purified from
      parotid gland saliva. Mutagenesis with ethyl methanesulfonate preceded enrichment
      for cells nonreactive with PRPs by successive adsorptions with PRP-treated latex
      beads. Screening was accomplished by random selection of 250 isolated colonies
      from each of four enrichment cycles and reaction with PRP-treated latex beads in
      microtiter plates. Two mutants of independent origin were examined for adherence
      to hydroxyapatite treated with either PRPs, proline-rich glycoproteins,
      deglycosylated proline-rich glycoproteins, or whole saliva. Additional surface
      properties that were examined included agglutination with polyclonal antisera to
      type 1 and type 2 fimbriae, agglutination by a monoclonal antibody to type 1
      fimbriae that inhibits adherence of the parent strain to saliva-treated
      hydroxyapatite, the ability to bind monoclonal antibody to the type 1 fimbrial
      subunit, and lactose-reversible coaggregation with Streptococcus sanguis 34. Both
      mutants exhibited reduced binding to hydroxyapatite treated with whole saliva or
      salivary protein preparations but were still capable of reaction with antiserum
      to type 1 and type 2 fimbriae. In addition, these mutants possessed the ability
      to bind monoclonal antibody to the type 1 fimbrial subunit in amounts comparable
      to the amount bound by the parent strain but were not agglutinated by the
      adherence-inhibiting monoclonal antibody. When considered with previously
      published data, these results suggest that an adhesive molecule is probably
      associated with type 1 fimbriae and allows for the interaction of A. viscosus
      with constituents in the salivary pellicle.

PMID- 1347287
TI  - Fimbriation, capsulation, and iron-scavenging systems of Klebsiella strains
      associated with human urinary tract infection.
AB  - Thirty-two strains of Klebsiella pneumoniae and seven strains of Klebsiella
      oxytoca isolated from urinary tract infections in elderly adults were analyzed
      for capsular antigens, iron-scavenging systems, and fimbriation. All strains were
      capsulated. Twenty-seven different K antigens were identified among the strains,
      with no particular antigen dominating. All strains produced the iron-scavenging
      system enterochelin as analyzed by bioassay and DNA hybridization. In contrast,
      the aerobactin iron-sequestering system was not detected in any of the strains.
      All strains caused hemagglutination of tannin-treated human erythrocytes and
      reacted with an anti-type 3 fimbriae antiserum as well as in DNA hybridization
      with a type 3 fimbria-specific probe, indicating that the Klebsiella strains
      possessed this fimbrial type. Possession of type 1 fimbriae was analyzed by
      agglutination tests and by hybridization with DNA probes from two distinct
      Klebsiella type 1 fimbria gene clusters. Phenotypic expression of the type 1
      fimbriae was found in 29 of 32 K. pneumoniae strains, whereas 30 strains reacted
      with either of the two type 1 fimbrial cluster DNA probes. In K. oxytoca,
      however, only three of seven strains expressed type 1 fimbriae and reacted with
      the DNA probes. The type 3 fimbriae were found to bind to a fraction of
      epithelial cells exfoliated in normal human urine, whereas the type 1 fimbriae
      bound strongly to urinary slime. No inhibitors of type 3 fimbrial binding were
      detected in human urine.

PMID- 1347288
TI  - Identification of two porcine brush border glycoproteins that bind the K88ac
      adhesin of Escherichia coli and correlation of these glycoproteins with the
      adhesive phenotype.
AB  - In this study, we identified two brush border glycoproteins (210 and 240 kDa)
      that bind both K88ac+ Escherichia coli and purified K88ac adhesin. The
      specificity of these binding glycoproteins for the K88ac adhesin was demonstrated
      in studies in which the binding of 35S-labeled K88ac+ E. coli and biotinylated
      K88ac adhesin to these glycoproteins was blocked in the presence of a 100-fold
      molar excess of unlabeled K88ac adhesin but not in the presence of the K99
      adhesin. Pretreatment of adhesive brush borders with sodium metaperiodate
      destroyed both binding activities, indicating that the interaction between the
      K88ac adhesin and the binding glycoproteins requires the glycoprotein
      carbohydrate moiety. It was demonstrated previously that K88ac+ E. coli binds to
      adhesive brush borders but not to nonadhesive brush borders (R. Sellwood, R. A.
      Gibbons, G. W. Jones, and J. M. Rutter, J. Med. Microbiol. 8:405-411, 1975). In
      the present study, brush borders isolated from 10 different pigs were tested
      first for brush border adhesiveness and then for the presence of the binding
      glycoproteins. In all cases, the binding glycoproteins were detected only in the
      adhesive brush border preparations. These two binding glycoproteins may be the
      receptors used by K88ac+ ETEC to adhere to intestinal brush border cells. Their
      presence on adhesive brush borders and absence on nonadhesive brush borders may
      be the basis for resistance and susceptibility of pigs to K88ac+ ETEC infections.

PMID- 1347290
TI  - 1992 World Congress on Cell Culture and Tissue Culture. 20-25 June 1992,
      Arlington, VA. Abstracts.

PMID- 1347289
TI  - Passive protective effect of chicken egg yolk immunoglobulins against
      experimental enterotoxigenic Escherichia coli infection in neonatal piglets.
AB  - Passive protection of neonatal piglets against fatal enteric colibacillosis was
      achieved with powder preparations of specific antibodies against K88, K99, and
      987P fimbrial adhesins of enterotoxigenic Escherichia coli. The antibody powders
      were obtained by spray drying the water-soluble protein fraction of egg yolks
      from immunized hens after the lipid components were precipitated with an aqueous
      dispersion of acrylic resins (Eudragit L30D-55; Rohm pharma). The anti-K88, -K99,
      and -987P antibody preparations reacted specifically against the corresponding
      fimbrial antigens in an enzyme-linked immunosorbent assay. The orally
      administered antibodies protected in a dose-dependent fashion against infection
      with each of the three homologous strains of E. coli in passive immunization
      trials with a colostrum-deprived piglet model of enterotoxigenic E. coli
      diarrhea. Scanning electron microscopy revealed adherence of enterotoxigenic E.
      coli in intestinal epithelial surfaces of control piglets, whereas in treated
      piglets treated with high-titer antibodies, a resistance to bacterial adhesion
      was observed. An enzyme immunoassay with avidin-biotin complex demonstrated
      specific local antibody activity in target areas of the small intestines. In
      vitro, E. coli K88+, K99+, and 987P+ strains adhered equally to porcine duodenal
      and ileal epithelial cells but failed to do so in the presence of homologous anti
      fimbrial antibodies. Absorption of egg yolk antibodies with fimbrial
      immunosorbent removed the anti-fimbrial antibody fraction and reduced
      significantly the protective nature of the antibody preparation in a passive
      immunization experiment, suggesting that anti-fimbrial antibodies were the active
      components.

PMID- 1347291
TI  - Nadolol to treat aggression and psychiatric symptomatology in chronic psychiatric
      inpatients: a double-blind, placebo-controlled study.
AB  - BACKGROUND: Considerable evidence indicates that the lipophilic beta-blocker
      propranolol is useful in treating organically based aggression. This study looked
      at the efficacy of a more hydrophilic beta-blocker, nadolol, to treat aggression
      in chronic psychiatric inpatients. METHOD: Forty-one chronic psychiatric
      inpatients with an average of one aggressive outburst per week (defined by the
      Overt Aggression Scale [OAS]) were entered into a double-blind, placebo
      controlled study lasting 17 weeks. The OAS was used to track aggression on a per
      incident basis, while the Brief Psychiatric Rating Scale (BPRS) and the Clinical
      Global Impressions scale (CGI) were used to track clinical status. RESULTS:
      Nadolol subjects showed a significant decline in frequency of aggression compared
      with controls (p = .026) and a significant decline in the BPRS total score (p =
      .007) and in the subfactors "hostility and suspicion," "negative symptoms," and
      "signs of hyperarousal/tension." There was no significant change in CGI "severity
      of illness" ratings between groups, although the nadolol group was significantly
      improved from baseline at every subsequent time period while the placebo group
      was unchanged throughout the study. CONCLUSION: Nadolol is of significant benefit
      in the treatment of aggression in chronic psychiatric inpatients. This drug does
      penetrate the brain over time, but the success of a drug whose primary locus of
      action is peripheral may implicate a bimodal mechanism of action, i.e., a role
      for the CNS and the soma in the maintenance of aggression.

PMID- 1347292
TI  - A comparison of diagnostic criteria for neuroleptic malignant syndrome.
AB  - BACKGROUND: A variety of diagnostic criteria for neuroleptic malignant syndrome
      (NMS) have been used in clinical studies of this disorder, but it is not known if
      different criteria consistently identify NMS. This study examines agreement
      between three frequently used sets of diagnostic criteria in a series of possible
      NMS episodes. METHOD: All clinically suspected NMS episodes occurring at a large
      tertiary psychiatric facility during a 6-year period were evaluated by three
      different sets of diagnostic criteria. Agreement among these criteria was
      quantified statistically by means of the kappa and intraclass correlation
      coefficients. RESULTS: The NMS diagnostic criteria examined generally
      demonstrated only fair agreement with one another in the diagnosis of NMS.
      Agreement was best among these criteria when the "probable" category was
      employed. A complex interaction involving both definition and structure of
      individual diagnostic criteria and designation of criteria as major or minor
      appears to contribute to these findings. CONCLUSION: The published diagnostic
      criteria used in this study do not consistently identify NMS episodes and
      demonstrate different thresholds for assigning this diagnosis. These differences
      are not due solely to different definitions of individual criteria (e.g., fever).
      Possible implications of these findings for clinical practice and research are
      discussed.

PMID- 1347294
TI  - Purification and determination of glutamine synthetase by high-performance
      immunoaffinity chromatography.
AB  - High-performance immunoaffinity chromatography (HPIAC) with anti-glutamine
      synthetase polyclonal antibodies bound to epoxy-activated silica was used to
      purify and determine this enzyme from the cyanobacterium Synechocystis. A single
      step HPIAC procedure with cell-free extracts yielded electroporetically
      homogeneous glutamine synthetase. In the determination of glutamine synthetase by
      HPIAC a linear response in the range 10-60 micrograms of enzyme was observed.
      Recoveries of 70% of the loaded enzymatic activity and 100% of protein were
      obtained. The determination of glutamine synthetase protein by HPIAC was compared
      with that obtained by rocket immunoelectrophoresis. The chromatographic method is
      proposed as a possible alternative to other immunochemical quantitative
      techniques, particularly when non-limiting amounts of samples are available.

PMID- 1347293
TI  - Symptomatic predictors of ECT response in medication-nonresponsive manic
      patients.
AB  - BACKGROUND: Relations between pretreatment symptom ratings and ECT outcome were
      examined in acute manic patients admitted at a state psychiatric center who were
      nonresponsive to medication. METHOD: One or 2 days after undergoing pretreatment
      clinical ratings, patients were randomly assigned to intensive pharmacotherapy,
      right unilateral ECT, left unilateral ECT, or bilateral ECT. Patients who failed
      to respond to any of the first three treatment conditions were assigned to
      crossover bilateral ECT. Patients who failed to respond to a primary treatment
      condition other than bilateral ECT but refused crossover bilateral ECT and those
      in whom ECT was terminated due to an organic brain syndrome were not considered
      for this study. No psychotropic drugs were prescribed for 4-7 days before, or
      during, the course of ECT. Of the 24 patients who entered the study, 18 patients
      completed the protocol. Based on independent clinical assessments by two research
      psychiatrists, a favorable treatment response was defined as a complete recovery
      from manic episode that was sustained for 1 week during which no psychotropic
      medications were prescribed. RESULTS: ECT nonresponders were significantly more
      angry, irritable, and suspicious than ECT responders. Severity of mania and
      depression ratings at baseline were not related to ECT response. CONCLUSION:
      Symptoms associated with poor response to ECT may overlap with those that have
      been reported to predict nonresponse to treatment with lithium. Our evidence also
      may support the view that differential symptom patterns may predict treatment
      outcomes to ECT and carbamazepine, respectively, in manic patients who do not
      respond to treatment with lithium or neuroleptics.

PMID- 1347295
TI  - Changes in normal glycosylation mechanisms in autoimmune rheumatic disease.
AB  - To investigate potential mechanisms controlling protein glycosylation we have
      studied the interrelationship between lymphocytic galactosyltransferase (GTase)
      activity and serum agalactosylated immunoglobulin G levels (G(0)) in healthy
      individuals and patients with rheumatoid arthritis and non-autoimmune arthritis.
      In RA there was reduced GTase activity and increased G(0). A positive linear
      correlation between B and T cell GTase was found in all individuals. The
      relationship between GTase and G(0) was found to be positive and linear in the
      control population and negative and linear in the RA population. Sulphasalazine
      therapy maintained normal levels of GTase and caused a reduction in G(0) in the
      RA population. IgG anti-GTase antibodies (abs) were significantly increased in
      the RA population, whereas IgM anti-GTase abs were significantly decreased in
      both the RA and the non-autoimmune arthritis groups. These data describe a defect
      in RA lymphocytic GTase, with associated abnormal G(0) changes, which is
      corrected by sulphasalazine. A possible regulatory mechanism controlling
      galactosylation in normal cells is suggested, in which there is parallel control
      of B and T cell GTase. IgM anti-GTase abs may be integrated into this normal
      regulatory process. This is disrupted in RA, where the positive feedback between
      GTase and G(0) is lost and there is an associated increase in IgG anti-GTase abs,
      which may result from isotype switching as IgM anti-GTase abs are reduced. We
      suggest that these mechanisms are of relevance to the pathogenesis of RA, and
      that their manipulation may form part of a novel therapeutic approach.

PMID- 1347296
TI  - Genetic study of a new X-linked recessive immunodeficiency syndrome.
AB  - Seven forms of X-linked (XL) immunodeficiency have been described (XL
      agammaglobulinemia, XL severe combined immunodeficiency [SCID], Wiskott-Aldrich
      syndrome, XL chronic granulomatous disease, XL hyper-IgM syndrome with low IgG
      and IgA, and XL lymphoproliferative syndrome), and properdine deficiency.
      Although there are (some) phenotypic variants, diagnosis is relatively simple on
      the basis of clinical, immunological, and genetic characteristics. We studied a
      family in which several males were affected by severe infections and whose
      pedigree suggested recessive XL inheritance of an immunodeficiency. Immunologic
      and genetic studies (X inactivation patterns in females and restriction fragment
      length polymorphism [RFLP] segregation) were performed in order to characterize
      the immunodeficiency. The propositus, a 5-yr-old boy, was found to have a severe
      and progressive T- and B-cell functional immunodeficiency characterized by
      defective antigen-specific responses. No lymphocyte subsets or membrane anomalies
      were detected and the immunodeficiency did not correspond to usual XL forms.
      Studies of DNA from two of the informative females, the mother and one sister
      revealed nonrandom X chromosome inactivation of T cells and, partially, B cells
      but not PMN, a pattern similar to that observed in XL SCID carriers. RFLP studies
      identified a haplotype segregating with the abnormal locus that may be localized
      in the proximal part of the long arm of the X chromosome. We thus report the
      characterization of a new XL immunodeficiency that may correspond either to
      another XL locus or to an attenuated phenotype of XL SCID.

PMID- 1347297
TI  - Genetic linkage of type VII collagen (COL7A1) to dominant dystrophic
      epidermolysis bullosa in families with abnormal anchoring fibrils.
AB  - Epidermolysis bullosa (EB) in a group of genodermatoses characterized by the
      fragility of skin. Previous studies on the dystrophic (scarring) forms of EB have
      suggested abnormalities in anchoring fibrils, morphologically recognizable
      attachment structures that provide stability to the association of the cutaneous
      basement membrane to the underlying dermis. Since type VII collagen is the major
      component of the anchoring fibrils, we examined the genetic linkage of dominant
      dystrophic EB (EBDD) and the type VII collagen gene (COL7A1) locus, which we have
      recently mapped to chromosome 3p, in three large kindreds with abnormal anchoring
      fibrils. Strong genetic linkage of EBDD and COL7A1 loci was demonstrated with the
      maximum logarithm of odds (LOD) score of 8.77 at theta = 0. This linkage was
      further confirmed with two additional markers in this region of the short arm of
      chromosome 3, and these analyses allowed further refinement of the map locus of
      COL7A1. Since there were no recombinants between the COL7A1 and EBDD loci, our
      findings suggest that type VII collagen is the candidate gene that may harbor the
      mutations responsible for the EB phenotype in these three families.

PMID- 1347299
TI  - Valproate and mood disorders: perspectives. Summit conferences on the Treatment
      of Bipolar Disorders, July 27-28, 1990, Colorado Springs, Colorado and January 24
      27, 1991, Snowmass, Colorado.

PMID- 1347298
TI  - Tumor necrosis factor mediates experimental pulmonary edema by ICAM-1 and CD18
      dependent mechanisms.
AB  - (TNF alpha)-induced sequestration of neutrophils (PMN) in lungs and of the
      resultant PMN-dependent pulmonary edema. Guinea pig lungs perfused with Ringers
      albumin were challenged with TNF alpha (1,000 U/ml) for 90 min, followed by
      addition of fresh perfusate containing 2 x 10(7) human PMN. TNF alpha challenge
      caused sequestration of PMN in the pulmonary vascular bed as indicated by a
      threefold increase in lung tissue myeloperoxidase activity (MPO). The activation
      of the sequestered PMN with phorbol 12-myristate 13-acetate (PMA; 5 x 10(-9) M)
      produced threefold increases in pulmonary artery (Ppa) and pulmonary capillary
      hydrostatic (Pcap) pressures, and twofold increases in lung wet-to-dry weight
      (W/D) ratio and capillary filtration coefficient (Kf,c) over baseline. TNF alpha
      prestimulation was required for these responses since activation of PMN with PMA
      in control lungs produced smaller increases in Ppa and Pcap (P less than 0.01)
      and did not change the W/D and Kf,c. TNF alpha prestimulation also induced the
      expression of intercellular adhesion molecule (ICAM-1) on pulmonary vascular
      endothelial cells. Monoclonal antibodies (mAbs) to the neutrophil CD18 integrin
      (beta-chain of CD11/CD18 complex) (mAb IB4) and to its endothelial cell ligand
      ICAM-1 (mAb RR1/1) were used to examine the role of PMN adhesion in the TNF alpha
      induced responses. Pretreatment of PMN with mAb IB4 prevented PMN uptake and
      increases in Ppa, Pcap, Kf,c, and W/D ratio. Addition of mAb RR1/1 to the
      perfusate reduced PMN uptake by 58%, and prevented the increases in Ppa, Pcap,
      Kf,c, and W/D ratio, as with mAb IB4. The findings indicate that TNF alpha
      prestimulation of lungs mediates PMN uptake and that this requires the expression
      of ICAM-1 and its interaction with CD18 integrin on PMN. The activation of PMN
      sequestered by ICAM-1-dependent mechanism contributes to the development of
      pulmonary vascular injury and edema.

PMID- 1347300
TI  - Deletion of antigen-specific immature thymocytes by dendritic cells requires LFA
      1/ICAM interactions.
AB  - An in vitro assay was used for assessing the participation of various cell
      surface molecules and the efficacy of various cell types in the deletion of Ag
      specific immature thymocytes. Thymocytes from mice expressing a transgenic TCR
      specific for the male Ag presented by the H-2Db class I MHC molecule were used as
      a target for deletion. In H-2d transgenic mice, cells bearing the transgenic TCR
      are not subjected to thymic selection as a consequence of the absence of the
      restricting H-2Db molecule but, nevertheless, express this TCR on the vast
      majority of immature CD4+8+ thymocytes. In this report we show that CD4+8+
      thymocytes from H-2d TCR-transgenic mice are preferentially killed upon in vitro
      culture with male APC; DC were particularly effective in mediating in vitro
      deletion when compared with either B cells or T cells. Deletion of CD4+8+
      thymocytes by DC was H-2b restricted and could be inhibited by mAb to either LFA
      1 alpha or CD8. Partial inhibition was observed with mAb to ICAM-1, whereas mAb
      to CD4 and LFA-1 beta were without effect. These results are the first direct
      evidence of LFA-1 involvement in negative selection and provide further direct
      support for the participation of CD8/class I MHC interactions in this process.
      Like the requirements for deletion, activation of mature male-specific CD4-8+ T
      cells from female H-2b TCR-transgenic mice was also largely dependent on Ag
      presentation by DC and required both LFA-1/ICAM and CD8/class I MHC interactions;
      these results support the view that activation and deletion may represent
      maturation stage-dependent consequences of T cells encountering the same APC.
      Finally, our results also support the hypothesis that negative selection
      (deletion) does not require previous positive selection because deletion was
      observed under conditions where positive selection had not occurred.

PMID- 1347301
TI  - Thymocytopoiesis is maintained by blood-borne precursors throughout postnatal
      life. A study in parabiotic mice.
AB  - This study was designed to resolve the long standing controversy as to whether
      hematogenous precursors or resident intrathymic precursors maintain
      thymocytopoiesis in postnatal life. The kinetics of thymic chimerism was examined
      over a 21-wk period in 105 pairs of nonirradiated, Thy-1-alloantigen-disparate,
      parabiotic B10.S mice. Thymic chimerism reached reached maximum levels of 25% in
      the Thy-1b and 16% in the Thy-1a partners (mean 20.5% and 9.8%, respectively) 6
      to 7 wk after parabiotic union. Most of the donor-origin thymocytes were located
      in the thymus cortex and expressed high levels of Thy-1 Ag and terminal
      deoxynucleotidyl transferase. Thymic chimerism did not reach 50% because
      circulating prothymocytes, unlike peripheral T cells, do not distribute randomly
      in the blood of parabiotic partners. This was shown in irradiated pairs of Thy-1
      alloantigen-identical parabiotic mice, one member of which was injected i.v. with
      Thy-1-alloantigen-disparate bone marrow cells. Only 10% of the total donor-origin
      prothymocyte activity was detected in the opposite parabiont 72 h later.
      Similarly, the level of thymic chimerism in nonirradiated, Thy-1-alloantigen
      disparate parabionts closely corresponded to the donor: host ratio of
      prothymocytes in the blood (i.e., between 10 and 20%), as determined directly by
      an intrathymic adoptive transfer assay. The continued dependence of thymic
      chimerism on blood-borne precursors was formally demonstrated by surgically
      separating mice 9 wk after parabiosis. Twelve weeks later, thymic chimerism was
      50 to 80% lower in the separated parabionts than in sham-operated controls. The
      possible role of "stress" in initiating or maintaining thymic chimerism during
      parabiosis appeared to be excluded by the existence of similar kinetics of
      thymocytopoiesis (including the onset of thymic involution) in parabiotic and
      nonparabiotic mice; and by the occurrence of similar levels of thymic chimerism
      in adrenalectomized and nonadrenalectomized parabiotic mice. Thus these
      experiments demonstrate that the maintenance of thymocytopoiesis in postnatal
      life, as in prenatal life, is primarily dependent upon blood-borne prothymocytes,
      and that intrathymic precursors are replaced at an average rate of 2 to 3%/day.

PMID- 1347302
TI  - Kinetics of anti-CD4-induced T helper cell depletion and inhibition of function.
      Activation of T cells by the CD3 pathway inhibits anti-CD4-mediated T cell
      elimination and down-regulation of cell surface CD4.
AB  - In vivo treatment with anti-CD4 antibody profoundly suppresses a number of T cell
      dependent responses and is clinically useful in the treatment of certain mouse
      models of autoimmune disease. Treatment with anti-CD4 antibody will inactivate
      and can deplete CD4 T cells, but the mechanisms responsible for these effects are
      incompletely understood. When mouse spleen cells were exposed in vitro to both
      SRBC and monoclonal anti-CD4, there was 55% reduction of the anti-SRBC response.
      If cultures were preincubated with anti-CD4 for 48 h before in vitro challenge,
      the reduction was greater than 80%. When unfractionated spleen cells were
      cultured with anti-CD4 for 96 h, there was actual elimination of CD4 cells in
      these cultures since virtually all CD3+ cells were CD8+. Activation of T cells by
      exposure to anti-CD3 rendered them resistant to antibody-mediated CD4 depletion.
      This resistance to CD4 depletion was seen even in cultures that were pretreated
      with anti-CD4 for as long as 24 h before anti-CD3 exposure. In cultures of
      purified T cells, anti-CD4 did not eliminate CD4 T cells. However, culture of T
      cells with macrophage-rich adherent cells and anti-CD4 resulted in elimination of
      CD4 T cells. Thus, it appears that macrophages play a role in anti-CD4-induced T
      cell elimination. While anti-CD4 did not eliminate CD4 cells from a population of
      purified T cells, there was profound down-regulation of cell surface CD4.
      Activating T cells with immobilized anti-CD3 before addition of anti-CD4
      prevented down-regulation of CD4. These experiments demonstrate that T cell
      activation by anti-CD3 renders the activated cells resistant to antibody-induced
      CD4 down-regulation and to antibody-induced CD4 T cell depletion. These findings
      may have relevance to the application of anti-CD4 therapy in human diseases that
      are mediated by activated Th cells.

PMID- 1347303
TI  - Extrathymic T cell maturation. Phenotypic analysis of T cell subsets in nude mice
      as a function of age.
AB  - T cell maturation in an extrathymic environment has been studied using as a model
      the congenitally athymic nude mouse. Phenotypic analyses as a function of age
      were conducted on lymphocytes obtained from the spleens and lymph nodes of nude
      mice through use of mAb recognizing T cell surface markers and multiparameter
      flow cytometry. The data show that nude mice accumulate increasing numbers of
      lymphocytes bearing Thy-1, CD3, CD4, and CD8 with age characterized by a
      progression from heterogeneous dim to more homogeneous bright expression. In
      contrast, the expression of heat-stable Ag (HSA), a marker of immature
      thymocytes, decreases with age. By analogy to intrathymic maturation, spleens and
      lymph nodes in nude mice contain T cells defined as immature, transitional, and
      mature based on the expression of these markers. Although the proportion of CD4+
      and CD8+ T cells associated with bright CD3 expression increases with age, at no
      age are significant numbers of CD4+8+ cells observed, in contrast to intrathymic
      T cell maturation. In addition to the frequently observed inversion in the ratio
      of CD4 to CD8, the CD8 T cell subpopulation in older nude mice contains mainly
      mature cells (CD8+, CD3+, HSA-) whereas only 50% of CD4+ T cells express the
      mature (CD4+, CD3+, HSA-) phenotype. At any age, the spectrum of phenotypes
      observed indicates that lymph nodes contain more mature T cells than spleen,
      suggesting a role for environmental Ag in driving extrathymic maturation, a
      process occurring most efficiently among CD8+ T cells. Because extrathymic
      maturation mirrors some but not all aspects of the intrathymic pathway, we
      propose that the nude mouse may be a useful model for further dissecting those
      interactions crucial to establishing the T cell repertoire in euthymic
      individuals as well as elucidating the contribution of extrathymically derived T
      cells to the peripheral immune system.

PMID- 1347304
TI  - Regulation of the expression of ICAM-1 on human monocytes and monocytic tumor
      cell lines.
AB  - In this study we investigated the mechanisms regulating expression of ICAM-1 that
      plays an important role for Ag presentation, on peripheral blood monocytes, and
      three myelomonocytic cell lines representing different stages of monocyte
      maturation. ICAM-1 expression on freshly isolated monocytes was low in all donors
      tested. After 16- to 20-h incubation, about a 20-fold increase was observed,
      whereas ICAM-1 expression on lymphocytes did not change. This marked increase in
      Ag expression was specific for ICAM-1, because expression of other monocyte Ag
      remained unchanged (alpha-chain of lymphocyte function-associated Ag-1) or
      decreased (ICAM-2, alpha-chains of CR3 and CR4, their common beta-chain and Fc
      gamma RI) during overnight incubation; only HLA-DR showed a slight increase.
      Enhanced expression of ICAM-1 was not caused by adherence; it was also not due to
      trace amounts of IFN-gamma possibly present under our culture conditions.
      Endotoxin contamination of the medium was excluded as a cause for the enhanced
      expression, and neither LPS nor its antagonist polymyxin B were able to alter
      ICAM-1 expression. Whole blood culture almost completely prevented up-regulation
      of ICAM-1 expression, thus apparently mimicking the in vivo situation. Culture of
      monocytes together with other PBMC had no significant influence on monocyte ICAM
      1 levels. From 12 different cytokines tested for their ability to modulate
      "spontaneous" up-regulation of ICAM-1 in culture, only IFN-gamma was found to
      increase expression about twofold. This effect was also observed in whole blood
      culture. All other cytokines had no significant effect. In contrast, ICAM-1
      expression on two of the three cell lines (KG1 and HL60) was inducible by TNF
      alpha to a much higher degree than by IFN-gamma, whereas the results with U937
      were comparable with those obtained for normal monocytes. The protein- and RNA
      synthesis inhibitors cycloheximide and actinomycin D prevented expression of ICAM
      1 in a dose-dependent fashion. In Northern blot experiments no difference in the
      amounts of mRNA was observed between freshly isolated and cultured monocytes,
      indicating that "spontaneous" induction of ICAM-1 is regulated at a
      posttranscriptional level. In contrast, stimulation with IFN-gamma caused a
      significant increase of detectable RNA comparable to that observed for Ag
      expression. These results disclose a very special regulation of ICAM-1 expression
      on monocytes which could be consistent with the view that ICAM-1 is actively down
      regulated in vivo until the monocyte leaves the circulation.

PMID- 1347305
TI  - CD8+ T cells can be primed in vitro to produce IL-4.
AB  - IL-4 production by T lymphocytes from naive mice in response to stimulation by
      plate-bound anti-CD3 is concentrated among CD4+ T cells. In vitro stimulation of
      lymph node T cells with anti-CD3 plus IL-2 and IL-4 strikingly increases the
      frequency of cells that produce IL-4 in response to subsequent stimulation with
      anti-CD3 plus IL-2. Separation of these primed cell populations into CD4+ and
      CD8+ T cell by cell sorting reveals that the frequency of IL-4-producing cells in
      both population is similar. Verification that CD8+ T cells produce IL-4 is
      provided by the capacity of anti-IL-4 mAb to inhibit the response of the
      indicator cell line to the growth factor produced by the primed cells and by
      detection of IL-4 by an IL-4-specific ELISA. The in vitro "priming" of CD8+ T
      cells to produce IL-4 is not dependent on the presence of CD4+ T cells because
      highly purified CD8+ T cells can be stimulated to develop into cells capable of
      producing IL-4 by culture with plate-bound anti-CD3 plus IL-2 and IL-4.

PMID- 1347306
TI  - IL-2 and a contact-mediated signal provided by TCR alpha beta + or TCR gamma
      delta + CD4+ T cells induce polyclonal Ig production by committed human B cells.
      Enhancement by IL-5, specific inhibition of IgA synthesis by IL-4.
AB  - To study the role of T cells in T-B cell interactions resulting in isotype
      production, autologous purified human splenic B and T cells were cocultured in
      the presence of IL-2 and Con A. Under these conditions high amounts of IgM, IgG,
      and IgA were secreted. B cell help was provided by autologous CD4+ T cells
      whereas autologous CD8+ T cells were ineffective. Moreover, CD8+ T cells
      suppressed Ig production when added to B cells cocultured with CD4+ T cells.
      Autologous CD4+ T cells could be replaced by allogeneic activated TCR gamma
      delta,CD4+ or TCR alpha beta,CD4+ T cell clones with nonrelevant specificities,
      indicating that the TCR is not involved in these T-B cell interactions. In
      contrast, resting CD4+ T cell clones, activated CD8+, or TCR gamma delta,CD4-,CD8
      T cell clones failed to induce IL-2-dependent Ig synthesis. CD4+ T-B cell
      interaction required cell-cell contact. Separation of the CD4+ T and B cells by
      semiporous membranes or replacement of the CD4+ T cells by their culture
      supernatants did not result in Ig synthesis. However, intact activated TCR alpha
      beta or TCR gamma delta,CD4+ T cell clones could be replaced by plasma membrane
      preparations of these cells. Ig synthesis was blocked by mAb against class II MHC
      and CD4. These data indicate that in addition to CD4 and class II MHC Ag a
      membrane-associated determinant expressed on both TCR alpha beta or TCR gamma
      delta,CD4+ T cells after activation is required for productive T-B cell
      interactions resulting in Ig synthesis. Ig production was also blocked by mAb
      against IL-2 and the IL-2R molecules Tac and p75 but not by anti-IL-4 or anti-IL
      5 mAb. The CD4+ T cell clones and IL-2 stimulated surface IgM-IgG+ and IgM-IgA+,
      but not IgM+IgG- or IgM+IgA- B cells to secrete IgG and IgA, respectively,
      indicating that they induced a selective expansion of IgG- and IgA-committed B
      cells rather than isotype switching in Ig noncommitted B cells. Induction of Ig
      production by CD4+ T cell clones and IL-2 was modulated by other cytokines. IL-5
      and transforming growth factor-beta enhanced, or blocked, respectively, the
      production of all isotypes in a dose-dependent fashion. Interestingly, IL-4
      specifically blocked IgA production in this culture system, indicating that IL-4
      inhibits only antibody production by IgA-committed B cells.

PMID- 1347307
TI  - In vitro induction of CD8 expression on thymic pre-T cells. I. Transforming
      growth factor-beta and tumor necrosis factor-alpha induce CD8 expression on CD8-
      thymic subsets including the CD25+CD3-CD4-CD8- pre-T cell subset.
AB  - We previously reported that IL-7 maintains the viability and differentiation
      potential of CD25 (IL-2R p55) positive CD3-CD4-CD8- thymic pre-T cells in vitro.
      This culture system is suitable for studying signals that regulate
      differentiation of T cell precursors in the thymus. In this study, we screened
      cytokines for their capacity to induce CD4 or CD8 in murine thymic pre-T cells
      cultured with IL-7. Of 15 cytokines tested, only transforming growth factor (TGF
      beta) and TNF-alpha induced CD8 (Lyt-2), while no cytokine was able to induce CD4
      on CD25+CD3-CD4-CD8- thymocytes. The combination of TGF-beta and TNF-alpha was
      synergistic, and the majority of cells recovered after 2 to 3 days in culture
      expressed CD8 (but not CD3 or CD4). A similar effect of TGF-beta and TNF-alpha
      was observed using day-15 fetal thymocytes, CD3+CD4-CD8- or CD3+CD4+CD8- adult
      thymocytes, although the combination of these cytokines resulted in an additive
      rather than a synergistic effect in these subsets. In contrast, neither TGF-beta
      nor TNF-alpha induced CD8 expression on splenic CD4+CD8- T cells. These
      observations suggest a role for these cytokines in the induction of CD8
      expression in CD8- thymocyte subsets including CD3-CD4-CD8- thymic pre-T cells.

PMID- 1347308
TI  - Roles of beta 2 integrins of rat neutrophils in complement- and oxygen radical
      mediated acute inflammatory injury.
AB  - The roles of beta 2 integrin molecules in neutrophil accumulation and tissue
      injury have been examined by the use of antibodies that are reactive with human
      CD11b and CD18 and cross-react with the homologous epitopes on rat neutrophils.
      Adherence to rat pulmonary artery endothelial cells by human neutrophils and
      endothelial cell killing by phorbol ester-activated human neutrophils required
      CD11b, CD11c, and CD18. Companion adherence studies between rat neutrophils and
      endothelial cells revealed a requirement for both CD11b and CD18. Neither anti
      CD11b nor anti-CD18 depressed in vitro responses (O2- generation and chemotactic
      migration) of rat neutrophils. The accumulation of neutrophils in glycogen
      induced peritoneal exudates was diminished substantially in rats treated with
      either anti-CD18 or anti-CD11b. In oxidant-mediated acute lung injury induced by
      rapid intravascular infusion of cobra venom factor, treatment of rats with either
      anti-CD18 or anti-CD11b significantly attenuated injury as assessed by increases
      in vascular permeability and hemorrhage. These protective effects correlated
      morphologically with diminished adhesion of neutrophils to interstitial
      intrapulmonary capillary endothelial cells. In studies of immune complex (BSA
      anti-BSA)-induced alveolitis and dermal vasculitis, anti-CD18 had protective
      effects at all doses of anti-BSA employed. The protective effects of anti-CD18
      correlated with diminished neutrophil accumulation in tissues at lower doses of
      anti-BSA. Although anti-CD11b was not effective under the same experimental
      conditions, intratracheal administration of this antibody conveyed protection
      against immune complex-induced lung injury, suggesting that both CD11b and CD18
      are required for the full expression of injury. The current studies also
      demonstrated that when surface-bound IgG immune complexes were treated with fresh
      rat serum, the increment in O2- and TNF alpha generated by alveolar macrophages
      was suppressed by anti-CD18, but not by anti-CD11b, suggesting a heretofore
      unrecognized role for CD18 in the O2- and TNF-alpha responses of alveolar
      macrophages. Thus, neutrophil beta 2 integrins play a requisite role for the full
      expression of complement-dependent and oxygen radical-mediated injury of the lung
      and dermal vasculature.

PMID- 1347309
TI  - Phenotypic and functional studies on ocular T cells during herpetic infections of
      the eye.
AB  - Herpetic stromal keratitis an inflammatory disease of the eye resulting from
      herpes simplex virus type 1 infection, is a common cause of blindness. The
      disease is generally considered to represent an immunopathologic response, but
      the exact mechanism remains in doubt and is subject to debate. We have
      investigated the nature of inflammatory cells in the eye and have isolated ocular
      cells to establish their phenotype and determine some of their functions. By
      means of immunocytochemistry and cytofluorography, the only T lymphocyte subset
      detectable at any stage of infection of BALB/c mice were CD4+ cells. However CD8+
      T cells were readily detectable in draining lymph nodes (DLN). Assays for cells
      with HSV-1-specific cytotoxic function of both CD4+ class II restricted and CD8+
      class I-restricted activity were performed. Although in DLN both cell types were
      found, among ocular cells only CD4+ cytotoxic cells were evident. The frequencies
      of CD4+ CTL-precursor in eyes were determined and found to be at least 8- to 10
      fold less than found in DLN. The number of CTL-precursor in an individual eye was
      estimated to be 20 or less. Our results further support the notion that CD4+
      mediate the immunopathology of herpetic stromal keratitis, but on quantitative
      grounds cast doubt on the idea that cytotoxicity is the principal mechanism
      involved.

PMID- 1347310
TI  - A new serotype of Bacillus thuringiensis from Colombia toxic to mosquito larvae.
AB  - During a survey conducted in Colombia a new isolate of Bacillus thuringiensis
      that showed toxicity toward Culex quinquefasciatus, Cx. pipiens, Aedes aegypti,
      and Anopheles stephensi larvae was isolated. Parasporal crystals were spherical
      in shape and showed a great degree of similarity with those produced by the
      reference strain of Bacillus thuringiensis subsp. israelensis. Supernatant
      fraction of the whole culture was not toxic, and heat-stable exotoxin production
      was negative. Catalase, urease, arginine dihydrolase, amylase, lecithinase,
      acetyl-methyl-carbinol, and gelatinase production were positive. Hemolysis on
      sheep blood agar was alpha-type. The isolate 163-131 showed natural resistance to
      azolocillin and was sensible to cephoperazone, cephalotin, nalidixic acid, and
      trimetoprin sulfametoxazole. Flagellar agglutination showed a specific H 30
      antigen which allows individualization of this strain as a new serotype and the
      subspecies name of medellin is proposed.

PMID- 1347311
TI  - Effects of in vivo T lymphocyte subset depletion on mycobacterial infections in
      mice.
AB  - The relative importance of CD4+ and CD8+ T cell subsets in the expression of
      acquired resistance to systemic infection by Mycobacterium kansasii was
      determined. T cell subsets were depleted in thymectomized C57BL/6 mice by the
      intravenous administration of monoclonal antibodies directed against the relevant
      T cell determinants. Depletion of the CD4+ subset exacerbated the severity of the
      infection in intravenously challenged mice. This effect was apparent in the first
      2 weeks of the infection and persisted throughout the 12 weeks of the study. On
      the other hand, depletion of the CD8+ cells had no apparent effect on the growth
      curves. Infections by Mycobacterium tuberculosis Erdman or bacille Calmette
      Guerin (BCG) Pasteur were also substantially enhanced by CD4 depletion, but not
      by the depletion of CD8+ cells. The effect of subset depletion on infections by
      M. tuberculosis and BCG was examined in both innately susceptible C57BL/6 mice
      and innately resistant B6D2 mice.

PMID- 1347312
TI  - Soluble TNF and membrane TNF expressed on CD4+ T lymphocytes differ in their
      ability to activate macrophage antileishmanial defense.
AB  - In our studies of host defense against the intracellular parasite Leishmania
      major, we obtained evidence for a novel mechanism of macrophage activation for
      antimicrobial defense that involves direct cell contact between CD4+ T
      lymphocytes and Leishmania-infected macrophages. The mechanism is distinctive as
      it does not involve secretion of lymphokines but is apparently mediated by the
      membrane-anchored form of tumor necrosis factor (mTNF; approximately 50-60 kd)
      present on the surface of the effector T lymphocytes. Furthermore, it is not
      cytotoxic to the host cell and its expression is antigen specific and genetically
      restricted. We prepared a Leishmania-specific cloned T-T cell hybridoma line 1B6
      (CD4+, TH1) that expresses membrane-bound TNF but does not secrete TNF or other
      macrophage activators. We now report that 1B6 cells can activate antileishmanial
      defense in inflammatory macrophages, whereas soluble recombinant murine TNF
      (sTNF) alone is unable to do so. On the other hand, both 1B6 cells and sTNF can
      act synergistically with recombinant murine interferon-gamma (IFN-gamma, a known
      soluble macrophage-activating factor) in activating antimicrobial defense and NO2
      release. The effects of 1B6 alone and the synergistic effects of 1B6 and IFN
      gamma or sTNF and IFN-gamma are arginine dependent. These results suggest that
      mTNF may be more efficient than sTNF in macrophage activation and that contact
      with effector CD4+ lymphocytes that express mTNF may be an important mechanism of
      host defense.

PMID- 1347313
TI  - Differential effects of CD4+ and CD8+ cells in acute, systemic murine candidosis.
AB  - Monoclonal antibody (mAb) depletion was used to assess contributions of CD4+ and
      CD8+ cells in resistance to systemic murine Candida albicans infection. Depletion
      of CD8+ cells did not influence either survival or mean survival time (MST);
      however, depletion of CD4+ cells significantly enhanced both survival and MST.
      Combined depletion of both CD4+ and CD8+ cells significantly lengthened the MST
      but did not enhance survival. A protective influence of CD8+ cells could be
      deduced but, to be manifested, required depletion of an overshadowing
      immunopathologic CD4+ response.

PMID- 1347314
TI  - Porcine skeletal muscle myofibrillar protein synthesis is stimulated by
      ractopamine.
AB  - Thirty-two 64-kg individually penned barrows were fed protein at 130 or 170 g/kg
      diet and ractopamine at 0 or 20 mg/kg in a randomized complete block design for
      28 d. Fractional synthesis rates of myofibrillar, sarcoplasmic and connective
      tissue proteins in longissimus dorsi, biceps femoris and gastrocnemius muscles
      were examined by primed-continuous infusion of L-[ring-2,6-3H(N)]phenylalanine
      over a 4-h period. Fractional synthesis, accretion and breakdown rates of protein
      in the muscles were not affected by dietary ractopamine, regardless of whether
      estimated on the basis of plasma or tissue homogenate specific activity. Absolute
      rates of protein synthesis (P less than 0.05) and breakdown (P less than 0.1) in
      biceps femoris muscle were both elevated by ractopamine feeding at 170 g
      protein/kg diet. Also in the diet containing 170 g protein/kg, ractopamine
      increased (P less than 0.05) protein contents of longissimus dorsi and biceps
      femoris muscles. Dietary ractopamine increased (P less than 0.05) fractional
      rates of synthesis of myofibrillar but not sarcoplasmic proteins in longissimus
      dorsi and biceps femoris muscles of pigs fed the 170 g protein/kg diet. This
      result demonstrates that ractopamine treatment results in a stimulation of
      myofibrillar protein synthesis.

PMID- 1347315
TI  - Nutrition, immunomodulation and AIDS. Symposium, American Institute of Nutrition
      Annual Meeting, Atlanta, Georgia, April 21-25, 1991.

PMID- 1347316
TI  - A preliminary trial of beta-carotene in subjects infected with the human
      immunodeficiency virus.
AB  - beta-Carotene is a nontoxic carotenoid with immunomodulating properties in
      animals and humans. Based on our observations in normal immunocompetent subjects,
      we studied the effects of this compound in 11 patients infected with the human
      immunodeficiency virus (HIV). Each subject received 60 mg of beta-carotene daily
      for 4 mo. Clinical and laboratory studies were obtained at baseline, every month
      while on treatment and for 2 mo after treatment. Increases in the percent of
      cells expressing Leu 11 (natural killer cells), Ia antigen and transferrin
      receptor (activated lymphocytes) were observed after 3 mo of treatment with beta
      carotene and diminished thereafter. Major changes were not seen in total
      lymphocyte count or in the percent of cells expressing CD11, CD8 or CD4 antigens.
      No clinical toxicity was observed. These data suggest that beta-carotene can
      modulate certain immune markers in HIV-infected subjects. Further study of this
      compound in HIV infection may be warranted.

PMID- 1347317
TI  - Immunosuppression and alteration of resistance to pulmonary tuberculosis in
      guinea pigs by protein undernutrition.
AB  - The impact of chronic moderate protein deficiency on resistance to pulmonary
      tuberculosis was studied in a guinea pig model. Inbred and outbred guinea pigs
      were maintained on isocaloric diets containing 30% or 10% ovalbumin, vaccinated
      with Mycobacterium bovis BCG vaccine and infected by the respiratory route with
      virulent Mycobacterium tuberculosis. Protein deficiency was associated with
      significant loss of dermal tuberculin hypersensitivity, reduced purified protein
      derivative (PPD)-driven lymphoproliferation in vitro and diminished interleukin-2
      production. The proportion of E rosette receptor (CD2) positive lymphocytes was
      significantly lower in the blood and thymus of low-protein guinea pigs. Increased
      levels of circulating anti-PPD antibodies were associated with loss of delayed
      hypersensitivity in protein-deprived animals. Immune complexes containing these
      antibodies may act on T cells bearing Fc receptors for immunoglobulin G (T gamma
      cells), which appear to exert a suppressive effect on antigen-induced
      lymphoproliferation of Tnon-gamma cells in vitro. These results imply an
      important immunoregulatory role for T gamma cells in tuberculosis and suggest one
      mechanism whereby resistance to tuberculosis is altered in protein malnutrition.

PMID- 1347318
TI  - Synthesis, cardiac electrophysiology, and beta-blocking activity of novel
      arylpiperazines with potential as class II/III antiarrhythmic agents.
AB  - A series of novel arylpiperazines have been prepared in an attempt to incorporate
      both class II (beta-receptor blocking) and class III antiarrhythmic properties in
      a single molecule. The key step in the preparation of the new compounds involves
      a regioselective heterocyclic ring formation. All but four compounds
      significantly prolonged action potential duration in canine cardiac Purkinje
      fibers (class III activity). All but one of the compounds demonstrated beta
      receptor affinity in a competitive binding assay and three had beta 1-receptor
      selectivity. Compared to sotalol, a reference class II/III agent, arylpiperazine
      7a (4-[(methylsulfonyl)amino]-N-[(4- phenylpiperazin-2-yl)methyl]benzamide)
      demonstrated beta 1-selectivity and was 1 order of magnitude more potent in the
      in vitro class III and the beta 1-receptor screens. Compound 7a was evaluated
      further and found to be effective in preventing programmed electrical stimulation
      induced arrhythmias in conscious dogs (class III activity) and against
      epinephrine-induced arrhythmias in halothane anesthetized dogs (class II
      activity).

PMID- 1347319
TI  - Synthesis and alpha-adrenergic activities of 2- and 4-substituted imidazoline and
      imidazole analogues.
AB  - Seven analogues of medetomidine and naphazoline were synthesized and evaluated
      for their alpha 1 (aorta) and alpha 2 (platelet) activities. The analogues were
      composed of 2- and 4-substituted imidazoles and imidazolines attached through a
      methylene bridge to either the 1- or 2-naphthalene ring system. In general the 1
      naphthalene analogues were the most potent inhibitors of epinephrine-induced
      platelet aggregation. Of considerable interest was the fact that the 1
      naphthalene analogues (2, 5-7) were partial agonists while the 2-naphthalene
      analogues (3, 8, 9) were antagonists in an alpha 1-adrenergic system (aorta).
      Thus, appropriately substituted naphthalene analogues of medetomidine and
      naphthazoline provide a spectrum of alpha 1-agonist, alpha 1-antagonist, and
      alpha 2-antagonist activity.

PMID- 1347320
TI  - Mushroom poisoning in infants and children: the Amanita pantherina/muscaria
      group.
AB  - The clinical features and management of nine cases of mushroom poisoning due to
      Amanita pantherina (eight cases) and Amanita muscaria (one case) admitted to a
      children's hospital are described. Most ingestions were in the toddler age group
      with males being more frequently involved. Symptoms occurred between 30-180 min
      with the onset of central nervous system depression, ataxia, waxing and waning
      obtundation, hallucinations, intermittent hysteria or hyperkinetic behavior.
      Vomiting was rare. Seizures or myoclonic twitching occurred in 4/9 patients, but
      was controlled with standard anticonvulsant therapy. No other anticholinergic or
      cholinergic signs were prominent. Recovery was rapid and complete in all
      patients.

PMID- 1347321
TI  - Changes in T-lymphocyte subsets in intravenous drug users with HIV-1 infection.
AB  - OBJECTIVE: To evaluate changes in T-cell subsets in prevalent human
      immunodeficiency virus type 1 (HIV-1) seronegative and seropositive intravenous
      drug users (IVDUs) and in HIV-1 seropositive IVDUs with known time of
      seroconversion. DESIGN: Cohort study with a median 18-month follow-up. SETTING:
      Community-based clinic established to study the natural history of HIV infection
      in IVDUs. SUBJECTS: Eight hundred fifty-nine self-referred IVDUs aged 18 through
      49 years who injected drugs within the last 10 years and who did not have an AIDS
      (acquired immunodeficiency syndrome)--defining illness; 152 were seronegative for
      HIV-1, 621 were seropositive, and 86 seroconverted during the study. OUTCOME
      MEASURES: Proportions and absolute numbers of lymphocytes and CD3, CD4, and CD8 T
      cells as determined at 6-month intervals by flow cytometry and complete blood
      cell counts with automated differential. RESULTS: Median numbers of CD4
      lymphocytes at enrollment were 1061/microL (1.06 x 10(9)/L) for seronegative
      IVDUs, 508/microL for seropositive IVDUs, and 733/microL for those who
      seroconverted (enrolled a median of 4.5 months after seroconversion); the
      corresponding figures for CD8 lymphocytes were 628, 894, and 889/microL,
      respectively. Median rates of decline in absolute numbers and percentages of CD4
      lymphocytes per 6 months were 7.6/microL (0.0%) for seropositive IVDUs and
      55.1/microL (1.9%) for IVDUs who seroconverted (median follow-up after
      seroconversion was 12 months). Multivariate regression analysis that incorporated
      the within-individual correlation of the CD4 lymphocyte counts showed no
      significant change in these cells over time and no change due to use of drugs.
      CONCLUSION: Our data suggest that progression of HIV-1 infection in IVDUs, as
      reflected in decline of CD4 cell counts, is no more rapid than that reported for
      other risk groups.

PMID- 1347322
TI  - [Proton pump inhibitors in the treatment of peptic ulcers resistant to H2
      receptor antagonists].
AB  - The aim of this study is to evaluate the therapeutic effect of proton pump
      inhibitors on peptic ulcers resistant to H2-receptor antagonists. Patients with
      ulcers resistant to at least 3 months treatment with standard or greater doses of
      H2-receptor antagonists were treated with 20 mg of omeprazole or 30 mg of
      lansoprazole, once daily, for 2 to 8 weeks. Endoscopy was performed every 2 weeks
      to confirm ulcer healing. Eleven of 28 (39%) gastric ulcers healed within 4 weeks
      and 20 (71%) within 8 weeks with omeprazole. Eight of 19 (42%) gastric ulcers
      healed within 4 weeks and 14 (74%) within 8 weeks with lansoprazole. All of the
      duodenal ulcer healed within 6 weeks with omeprazole or lansoprazole. No adverse
      effects were observed in this study. These results suggest that proton pump
      inhibitors are highly effective in the treatment of peptic ulcer resistant to H2
      receptor antagonists.

PMID- 1347323
TI  - [Movement of gastric acid secretion and influence of proton pump inhibitors on
      histamine H2 receptor antagonist resistant ulcer].
AB  - Treatment of peptic ulcers has become easier with the advent of H2 blockers.
      However, H2 resistant ulcer still remain. These cases were screened by 24 hr
      intragastric pH monitoring, which well reflects the status of gastric acid
      secretion. On the one hand, there were cases in which no nocturnal elevation in
      gastric pH was seen even after administration of H2 blocker (H2 blocker resistant
      ulcer). On the other hand, there were cases which were resistant to treatment
      with H2 blocker, although the gastric pH elevated. It is considered that
      omeprazole is effective for the former cases.

PMID- 1347324
TI  - [Endoscopic studies on refractory gastric ulcers, especially, linear ulcers,
      treated with proton pump inhibitor].
AB  - Seven patients with refractory gastric ulcers against H2-blocker therapy, were
      treated with omeprazole, and the endoscopic findings serially followed. Round
      ulcers improved steadily with treatment in two cases. However, healing of the
      ulcers was not complete and very small pin-point ulcers remained. Therefore, a
      prostaglandin E1 analogue was added at the 14 and 16th week of omeprazole
      therapy. The ulcers healed completely, two weeks later. In five cases with linear
      ulcers, one case discontinued the taking of omeprazole. The linear ulcers in the
      other four cases healed completely within 4 to 11 weeks. Endoscopically, some
      parts of the linear ulcers were initially scarred and the ulcers were divided
      into several short ulcers. The ulcers separated there after and healed
      respectively. These findings suggest that the healing process of linear ulcers
      may represent the reversed course of the developing process of linear ulcers. The
      results indicate that omeprazole is highly effective for the treatment of
      refractory gastric ulcers.

PMID- 1347325
TI  - [H2-receptor antagonist-refractory ulcer--its pathophysiology and role of proton
      pump inhibitors].
AB  - Among H2-receptor antagonist (H2RA)-refractory ulcers, non-responders that did
      not heal after 5 months therapy had high intraluminal pH in the basal condition
      and high sensitivity to inhibition of acid secretion by H2RA but possessed
      gastric mucosa to generate less prostaglandins. Combination therapy of PGE1
      analogue with H2RA healed these ulcers by 60%. Proton-pump inhibitor (PPI)
      exerted a complete inhibition of acid secretion in these patients and the rate of
      healing was 88%. Helicobacter pylori was present in the mucosa of all 4 ulcer
      patients refractory to treatment with PPI. The ulcers healed in 3 out of 4
      patients after eradication of H. pylori. It is suggested that PG supplement or
      complete inhibition of acid secretion is effective for ulcers in H2RA-non
      responders. PPI-refractory ulcers may relate to H. pylori infection.

PMID- 1347327
TI  - [Application of proton pump inhibitor to special conditions; Zollinger-Ellison
      syndrome].
AB  - Before the mid-1970s, the most reliable therapy for Zollinger-Ellison syndrome (Z
      E syndrome) was total gastrectomy since complete excision of gastrinoma is
      difficult in many cases due to multifocus and/or metastases. With the advent of
      H2-blockers gastric acid secretion can be controlled at safe levels (less than 10
      mEq/h), and patients with Zollinger-Ellison syndrome can be managed medically.
      The problem of therapy with H2-blockers however, is that large doses are usually
      required and that a marked tachyphylaxis is frequently noted during long-term
      treatment. Treatment with new antisecretory drug, proton pump inhibitor, has been
      shown to be highly effective with relatively high doses and without
      tachyphylaxis, although long-term experience is still limited.

PMID- 1347326
TI  - [Evaluation of the effect of proton pump inhibitors on stomal ulcer].
AB  - Four reports on proton pump inhibitors related to the clinical effects on stomal
      ulcer were reviewed. Two reports were on omeprazole and the other two on
      lansoprazole, carried out in the pre-marketing stage. They are compared with two
      reports on H2-receptor antagonists (famotidine and ranitidine), which were also
      done in the pre-marketing stage. It appears that the proton pump inhibitors bring
      more rapid ulcer healing than H2-receptor antagonists without severe side
      effects, and there seems to be no difference in clinical effect between
      omeprazole and lansoprazole.

PMID- 1347328
TI  - [Investigation of the therapeutic use of proton pump inhibitor (PPI) by
      measurement of 24 hour the intra-gastric pH].
AB  - The intragastric acidic condition were examined over 24 hours in 13 healthy
      volunteers to compare the inhibitory effect of PPI and of H2-antagonist on the
      acid secretion. Both PPI 15 mg and PPI 20 mg showed a stronger action on the acid
      inhibition than H2-antagonists. The morning PPI (20 mg) administration inhibited
      the acid secretion from noon the first day, and showed an even stronger effect on
      the fourth day (total PPI 80 mg). Evening PPI administration showed poorer
      effects than the morning. However, of this was due to a difference in the
      inhibitory effect in the daytime. The evening PPI administration showed effective
      acid inhibition at night, and nocturnal intra-gastric pH inversion appeared. It
      is suggested that the evening PPI administration is more suitable both the ulcer
      healing and food digestion in the curative stage.

PMID- 1347329
TI  - [Changes in the treatment of peptic ulcer following the development of proton
      pump inhibitors].

PMID- 1347330
TI  - [Proton pump inhibitors: their merits and demerits, and perspectives for future
      investigation].
AB  - Proton pump inhibitors have a potent antisecretory activity and are under
      development in many pharmaceutical companies. In this paper, the merits and
      demerits of the drugs, which have been revealed by experimental studies in humans
      and animals, are reviewed. Issues of the drugs which remain to be examined in the
      future are also discussed in reletion to their application in peptic ulcer
      patients. The issues include 1) genotoxicity of the drugs with long-term
      treatment; 2) their possible contribution to defensive factors of gastro
      intestinal mucosa; 3) their antimicrobial activity against Helicobacter pylori;
      4) interaction with the other drugs; etc.

PMID- 1347331
TI  - [Clinico-pharmacological evaluation of omeprazole, as a proton pump inhibitor,
      compared with H2-blockers].
AB  - We evaluated the safety, tolerance, pharmacokinetics and pharmacodynamics of
      omeprazole, a new anti-ulcer agent chiefly on the basis of our studies in healthy
      male volunteers. The type and incidence of side effects of omeprazole have been
      reported to be similar to those of H2-antagonists, and in our studies too,
      omeprazole was estimated to be safe and tolerable. Following single doses, the
      increase in AUC was not proportional to the increase in dosage. In the multiple
      dose study, the AUC was greater on day 7 than on day 1. This finding may be due
      to a partial saturation of first pass elimination. Repeated omeprazole treatment
      (20 mg once daily for 4 days) inhibited the basal and stimulated acid secretion.
      Though H2-blockers inhibit the basal and stimulated pepsin secretion, omeprazole
      inhibited the stimulated pepsin secretion only.

PMID- 1347332
TI  - [Double-blind controlled-clinical trials of lansoprazole in the treatment of
      peptic ulcer].
AB  - Two multicentre clinical trials of lansoprazole, a new proton pump inhibitor,
      were completed in patients with gastric and duodenal ulcer. Double-blind
      comparative studies with a beta-blocker, famotidine, in gastric ulcer (study 1)
      and in duodenal ulcer (study 2) were conducted. Study 1. A total of 316 cases of
      gastric ulcer, 158 for lansoprazole, 158 for famotidine were treated for eight
      weeks and the bollowing observed. Healing rates by endoscopic findings were 90%
      for lansoprazole and 72% for famotidine respectively, with a significant
      difference (p less than 0.01). Adverse events were observed in five cases in
      lansoprazole group, six cases in the famotidine group. Study 2. A total of 291
      cases of duodenal ulcer, 148 for lansoprazole, 143 for famotidine, were treated
      for six weeks. Healing rates by endoscopic fendings were 92% for lansoprazole and
      85% for famotidine respectively. Adverse effects were observed in 5.3% in the
      lansoprazole group, and 5.5% in the famotidine group.

PMID- 1347333
TI  - [Endoscopic stage classification of peptic ulcer and characterization of the
      healing process by proton pump inhibitors].
AB  - Proton pump inhibitors are highly effective for gastric acid secretion and have
      been shown to be superior to histamine H2-receptor antagonists. The superiority
      of proton pump inhibitors over H2-receptor antagonists was more pronounced in
      duodenal ulcers. Omeprazole reduced the time required by H2-receptor antagonists
      the healing of duodenal ulcers by 2/3 to 1/2. On the other hand, unusual
      endoscopic findings, such as shallow white coat or protrusion of the ulcer floor,
      were noted in the healing stage of gastric ulcers with H2-receptor antagonists.
      Whereas these findings were rarely seen with conventional drugs. Histologically,
      the protrusion was made up granulation tissue consisting of cell infiltration and
      renewed capillaries with or without regenerated epithelia. These unusual
      endoscopic findings may be observed in the peptic ulcers treated with proton pump
      inhibitors.

PMID- 1347334
TI  - [Endoscopic ultrasonographic study of gastric ulcer treated with proton pump
      inhibitor].
AB  - We examined 70 cases of gastric ulcer by endoscopic ultrasonography. Of these, 18
      cases were treated with proton pump inhibitor (PPI), another cases were treated
      with histamine H2 receptor antagonist or mucosal protective drugs. The Endoscopic
      cumulative healing rate at the eighth week was 71.4% in all gastric ulcers. On
      the other hand, all of gastric ulcers treated with PPI were healed within eight
      weeks endoscopically. Gastric ulcers which were revealed ultrasonographically to
      be refractory with were healed by PPI therapy. The length of the ulcer echo in
      gastric ulcers treated with PPI was shorter than that in gastric ulcer treated by
      other drugs. In spite of endoscopic scar findings, a wide ulcer echo was observed
      in some cases.

PMID- 1347335
TI  - [The influence of proton-pump inhibitors on the healing process of peptic ulcers-
      electronic endoscopic study].
AB  - It is highly important to analyze the of protonpump inhibitors on the healing
      process of peptic ulcers endoscopically since the use of proton-pump inhibitors
      is restricted in their period of usage. It is however, too early to evaluate
      proton-pump inhibitors as equal to or comparable to the many H2 blockers which
      have been tested basically and clinically. From the view-point of the number of
      clinical cases too, it is too early to conclude that the protonpump inhibitors
      are superior to previous H2 blockers. Most of the ear electronic endoscopic
      studies are highly conducted with the stereo-type electronic endoscopes except
      that on the regenerative epitheliums. The pictorial management of the
      regenerative epitheliums and intramucosal blood volume are not discussed in this
      paper, but results are expected to in the near future.

PMID- 1347336
TI  - Prophylaxis with carbon-adsorbed mitomycin against peritoneal recurrence of
      gastric cancer.
AB  - Attempts to prevent peritoneal carcinomatosis after surgery for gastric cancer by
      intraperitoneal administration of anticancer drugs have not been successful,
      largely because the drugs are not retained in the peritoneal cavity. We have
      assessed the prophylactic efficacy of a delayed-release preparation--mitomycin
      adsorbed onto activated charcoal (M-CH). 50 patients with gastric cancer and
      serosal infiltration were randomly assigned intraperitoneal treatment with M-CH
      (50 mg mitomycin intraoperatively) or no anticancer prophylaxis (control).
      Survival rates for the 3 years of follow-up were significantly higher among the
      24 M-CH recipients (1 was lost to follow-up) than among the 25 controls (p less
      than 0.01). There were significant differences in survival between the groups at
      1.5 years after randomisation (difference 34.6% [95% confidence interval 8.5
      60.8%]; p less than 0.01) and at 2.0, 2.5, and 3.0 years (41.7% [14.2-69.1%]; p
      less than 0.005). The concentration of mitomycin was significantly higher in
      peritoneal exudate than in plasma for 24 h after drug administration. Side
      effects were slight and well tolerated. Thus, peroperative intraperitoneal
      treatment with M-CH seems to improve survival after gastrectomy for gastric
      cancer, presumably by a prophylactic effect on peritoneal recurrence.

PMID- 1347337
TI  - Risk of Kaposi's sarcoma and sexual practices associated with faecal contact in
      homosexual or bisexual men with AIDS.
AB  - The causal agent of Kaposi's sarcoma is unknown. That the disorder is ten times
      more common in homosexual or bisexual men with the acquired immunodeficiency
      syndrome (AIDS) than in other human immunodeficiency virus (HIV) transmission
      groups suggests that a certain aspect of their behaviour exposes them to the
      agent or facilitates its spread. We therefore assessed social and demographic
      characteristics, including sexual behaviour, of 65 homosexual or bisexual men
      with AIDS from London. Sexual practices in which there was contact with partner's
      faeces before AIDS developed were the main determinants of Kaposi's sarcoma risk.
      Risk increased with frequency of insertive "rimming" (oral-anal contact):
      Kaposi's sarcoma developed in 18% of the men with AIDS who reported never having
      practised insertive rimming compared with 50% who practised it less than once a
      month, 73% between once a week and once a month, and 75% or more once a week (two
      sided exact p-value for trend less than 0.001). 45 men had been interviewed about
      their sexual practices before AIDS developed, and 20 were interviewed at the time
      the syndrome developed. The findings were similar and statistically significant
      when each group was analysed separately. The men with Kaposi's sarcoma also
      tended to be more sexually active and were more likely to engage in other sexual
      activities that entailed contact with faeces than were the men who had other
      features of AIDS only. Other behaviours and exposures, including the use of
      "poppers" (nitrite inhalants), were not related to Kaposi's sarcoma risk, after
      taking into account whether the subjects had practised insertive rimming. The
      data suggest that faecal-oral contact is the main route of transmission of the
      agent of Kaposi's sarcoma in homosexual or bisexual men with AIDS.

PMID- 1347339
TI  - Chronic neurodegenerative disease associated with HTLV-II infection.
AB  - Although human T-cell leukemia virus (HTLV) type I is known to cause a number of
      diseases, there has been no convincing evidence of pathological changes after
      infection with the related virus, HTLV-II. We have found an endemic focus of HTLV
      II infection among members of an American Indian population in New Mexico, USA.
      We set out to determine the pathological consequences of HTLV-II infection in
      this population and identified two sisters (aged 59 and 46 years) with a disease
      superficially resembling the myeloneuropathy induced by HTLV-I. These women had a
      syndrome similar to the olivopontocerebellar atrophy variant of multiple system
      atrophy, and HTLV-II infection was confirmed by western blot and the polymerase
      chain reaction. Thus, HTLV-II may, like HTLV-I, cause a progressive
      neurodegenerative disease.

PMID- 1347338
TI  - Efficacy of BCG vaccine against leprosy and tuberculosis in northern Malawi.
AB  - Protection afforded by BCG (bacillus Calmette-Guerin) vaccines against
      tuberculosis and leprosy varies widely between different populations. In the only
      controlled trial which assessed protective efficacy of BCG (Danish and Pasteur
      strains) against both diseases, there was slightly more protection against
      leprosy than against tuberculosis. We have studied the protective efficacy of BCG
      (Glaxo, freeze dried) vaccine against these two diseases in Karonga District,
      northern Malawi. BCG vaccination was introduced into this population in 1974.
      Prior information about BCG scar status was available for 83,455 individuals
      followed up between 1979 and 1989. 414 new cases of leprosy and 180 new cases of
      tuberculosis were found in this population over that period. Protection was
      estimated at 50% or greater against leprosy, and there was no evidence for lower
      protection against multibacillary (84%; 95% confidence interval 26% to 97%) than
      against paucibacillary (51%; 30% to 66%) disease. There was no statistically
      significant protection by BCG against tuberculosis in this population. These
      findings add to the evidence that BCG vaccines afford greater protection against
      leprosy than against tuberculosis.

PMID- 1347340
TI  - Atherosclerosis goes to the wall.

PMID- 1347341
TI  - Peripheral stem cells made to work.

PMID- 1347342
TI  - Rediscovering wormwood: qinghaosu for malaria.

PMID- 1347343
TI  - Hypomelanosis of Ito.

PMID- 1347344
TI  - Pestilent PCs.

PMID- 1347345
TI  - Subarachnoid haemorrhage.

PMID- 1347346
TI  - Intracerebral haemorrhage.

PMID- 1347347
TI  - Investigation of selected patients with hypertension by the rapid-sequence
      intravenous urogram.
AB  - The rapid-sequence intravenous urogram (IVU) has tended to fall from favour for
      investigating hypertension because of its perceived imprecision for detecting
      renovascular disease. However, no study has examined the value of the IVU as a
      screening test in appropriately selected patients. We have analysed the
      diagnostic yield of the rapid-sequence IVU in hypertensive patients selected for
      features suggesting renal or renovascular disease in a retrospective review of
      case records from a hypertension clinic. The IVU was abnormal in 27% (95% CI 21
      32%) of 241 consecutive patients. The most common abnormalities were chronic
      pyelonephritis (6%); proven renovascular disease (5%); stone (4%); possible
      renovascular disease and simple cyst (each 3%); hydronephrosis (2%); and tumour
      and active tuberculosis (each 1%). The IVU led to intervention aiming to correct
      hypertension in 5% (95% CI 2-8%) of patients, and revealed an abnormality needing
      intervention in its own right in 4% (95% CI 2-6%). The IVU led to unnecessary
      invasive investigation in 3% of cases. Individual abnormalities could not be
      predicted from the clinical or laboratory features. The initial investigation in
      hypertensive patients with suspected renal or renovascular disease should be a
      general purpose test able to detect a wide range of abnormalities. The rapid
      sequence IVU is the only single test capable of satisfying this requirement. In
      patients with features suggesting renovascular disease, a normal rapid-sequence
      IVU excludes renovascular disease with 93% probability, but is an imperfect
      screening test since it fails to diagnose about 20% of cases. Renal arteriography
      should be done despite a normal IVU when it is essential to exclude renovascular
      disease.

PMID- 1347348
TI  - Effect of high-dose intravenous immunoglobulin therapy on blood rheology.
AB  - Stroke has been reported after high-dose intravenous immunoglobulin (IVIG)
      therapy, so a study was conducted to find out what effect IVIG has on factors
      influencing blood flow. The influence of IVIG on plasma viscosity, blood
      viscosity, and erythrocyte aggregation was examined in vitro and in vivo. For the
      in-vitro experiments different amounts of IVIG were added to whole blood or
      plasma from healthy subjects. The in-vivo effects were assessed during five
      courses of treatment with IVIG (24-54 g/day) in 4 patients with chronic immune
      thrombocytopenia (ITP). Concentration of IgG infused correlated strongly with
      viscosity of plasma and whole blood, both in vitro and in vivo, and plasma
      viscosity increased to beyond the normal range after IVIG treatment. The changes
      in viscosity that occur after IVIG therapy can impair blood flow, and in patients
      at risk of cardiovascular and thromboembolic events they might be sufficient to
      produce myocardial infarction or stroke.

PMID- 1347349
TI  - Prevention vs cure in developing countries: the pendulum syndrome.

PMID- 1347350
TI  - France: compensation for post-transfusion HIV infection.

PMID- 1347351
TI  - European AIDS definition.

PMID- 1347352
TI  - Scientific and legal standards of proof in environmental personal injury cases.

PMID- 1347353
TI  - Testing an anti-HIV trio.

PMID- 1347354
TI  - Treating early breast cancer.

PMID- 1347355
TI  - Treating early breast cancer.

PMID- 1347356
TI  - Cereal-based oral rehydration solutions.

PMID- 1347357
TI  - Treating early breast cancer.

PMID- 1347358
TI  - Treating early breast cancer.

PMID- 1347359
TI  - Triazolam and violent deaths.

PMID- 1347360
TI  - Spontaneous reporting of adverse reactions to psychiatric drugs.

PMID- 1347361
TI  - Hyperpyrexia and rhabdomyolysis after MDMA ("ecstasy") abuse.

PMID- 1347362
TI  - Endotoxin antibody for sepsis in infants.

PMID- 1347363
TI  - Single-blind Mazzotti test for onchocerciasis.

PMID- 1347364
TI  - Flucloxacillin jaundice.

PMID- 1347365
TI  - Follow-up of patients with one kidney.

PMID- 1347366
TI  - Screening for osteoporosis.

PMID- 1347367
TI  - Screening for osteoporosis.

PMID- 1347368
TI  - Hypertension, in black and white.

PMID- 1347369
TI  - Counting birds, bees, and NCDs.

PMID- 1347370
TI  - S(+) versus racemic ibuprofen.

PMID- 1347371
TI  - Ethical emergencies and ethical consultations.

PMID- 1347372
TI  - Ethical emergencies and ethical consultations.

PMID- 1347373
TI  - Ethics and clinical research in anaesthesia.

PMID- 1347374
TI  - Insurance and HIV antibody testing.

PMID- 1347376
TI  - Methotrexate tablet confusion.

PMID- 1347375
TI  - Medical witness on trial.

PMID- 1347377
TI  - Prolonged resuscitation efforts.

PMID- 1347378
TI  - Cancer risk in laboratory workers.

PMID- 1347379
TI  - R1 anti-reticulin antibody as marker of subclinical gluten enteropathy.

PMID- 1347380
TI  - Kaposi's sarcoma and exposure to faeces.

PMID- 1347381
TI  - Kaposi's sarcoma and exposure to faeces.

PMID- 1347382
TI  - Use of cyclosporin for psoriasis in HIV-positive patient.

PMID- 1347383
TI  - In-vitro activity of zidovudine against Mycoplasma.

PMID- 1347384
TI  - ACE inhibitors and heart failure.

PMID- 1347385
TI  - ACE inhibitors and heart failure.

PMID- 1347386
TI  - Ear malformation in baby born to mother using tretinoin cream.

PMID- 1347387
TI  - ACE inhibitors and heart failure.

PMID- 1347388
TI  - ACE inhibitors and heart failure.

PMID- 1347389
TI  - Urapidil and enuresis.

PMID- 1347390
TI  - PTH(1-84) in hypercalcaemia of malignancy.

PMID- 1347391
TI  - Role of omental milky spots in the local immune response.

PMID- 1347392
TI  - Therapeutic window for 5-HT reuptake inhibitors.

PMID- 1347393
TI  - When is fever malaria?

PMID- 1347394
TI  - When is fever malaria?

PMID- 1347395
TI  - When is fever malaria?

PMID- 1347396
TI  - Chromosomal aberrations defining uveal melanoma of poor prognosis.

PMID- 1347397
TI  - Expansion of unstable DNA region in Japanese myotonic dystrophy patients.

PMID- 1347398
TI  - Coenzyme A esters of 2-aryloxyphenoxypropionate herbicides and 2-arylpropionate
      antiinflammatory drugs are potent and stereoselective inhibitors of rat liver
      acetyl-CoA carboxylase.
AB  - The CoA esters of diclofop, haloxyfop and fluazifop are up to 425-fold more
      potent than the corresponding unconjugated herbicides as inhibitors of rat liver
      acetyl-CoA carboxylase (EC 6.4.1.2); the most potent inhibitor is (R)-fluazifopyl
      CoA2 (Ki = 0.03 microM). The binding site is stereoselective for (R)-diclofop,
      the herbicidally active enantiomer, and for (R)-diclofopyl-CoA. The CoA esters of
      the antiinflammatory drugs ibuprofen and fenoprofen also strongly inhibit this
      carboxylase. (S)-Ibuprofenyl-CoA (Ki = 0.7 microM), the CoA ester of the
      enantiomer with antiinflammatory activity, is 15-fold more potent as an inhibitor
      than (R)-ibuprofenyl-CoA. These results suggest that some of the biological
      effects of these herbicides and antiinflammatory drugs in animals may be due to
      the inhibition of acetyl-CoA carboxylase by their acyl-CoA derivatives.

PMID- 1347399
TI  - Effects of rat pancreatic polypeptide on islet-cell secretion in the perfused rat
      pancreas.
AB  - Pancreatic polypeptide (PP) secretory cells are abundant in the islets of
      Langerhans. Results concerning the effects of exogenous PP on islet-cell
      secretion are controversial. This might be due in part to species specificity,
      given that most reports refer to studies performed using PP of bovine, porcine,
      or human origin in a heterologous animal model. Thus, we have investigated the
      influence of synthetic rat PP (80 nmol/L) on unstimulated insulin, glucagon, and
      somatostatin release, and on the responses of these hormones to glucose (11
      mmol/L) and to arginine (3.5 mmol/L) in a homologous animal model, the perfused
      rat pancreas. Infusion of rat PP (rPP) reduced unstimulated insulin release by
      35% (P = .03), and the insulin responses to glucose by 65% (P = .029) and to
      arginine by 50% (P = .026), without modifying glucagon output. rPP did not affect
      somatostatin secretion, either in unstimulated conditions or in the presence of
      11 mmol/L glucose. However, it induced a clear-cut increase in somatostatin
      release during 3.5 mmol/L arginine infusion. Our observation that rPP inhibited
      insulin secretion without affecting glucagon and somatostatin output points to a
      direct effect of PP on B-cell function. However, during aminogenic priming of the
      D cell, the inhibition of insulin output induced by rPP was accompanied by an
      increase in somatostatin release. Thus, in this circumstance, it might be
      considered that the blocking effect of PP on B-cell secretion could be, at least
      in part, mediated by a D-cell paracrine effect.

PMID- 1347400
TI  - Organization of immunoglobulin heavy chain constant and joining region genes in
      the channel catfish.
AB  - A channel catfish genomic lambda library was screened with CH and JH probes which
      were derived from our earlier sequence analyses on different full-length heavy
      chain cDNA clones. One clone, designated C7, contained a genomic insert of about
      18 kb and hybridized with specific probes for each of the four domains of the
      known C region gene as well as with different oligonucleotides specific for JH
      gene segments. Southern blot hybridization analysis identified a cluster of JH
      gene segments which are closely linked to the CH gene. Sequence analysis of the
      CH-proximal JH element, located about 1.9 kb upstream from the CH1 domain, showed
      that this element contains 5'-recombination signals typical of JH elements
      defined in higher vertebrates, i.e. a nonamer, a 24 bp spacer, and a heptamer.
      The coding region of this JH element was identical to that contained in the
      variable region sequence of a cDNA clone previously reported. Sequence analysis
      of the catfish JH-CH intron suggests that several sequences are present which
      appear similar to important transcriptional regulatory elements found within JH
      CH introns of higher vertebrates. These features include sequences similar to
      higher vertebrate enhancer elements and regulatory octamers. An additional
      feature reminiscent of some higher vertebrate heavy chain switch regions is a
      repetitive sequence area composed of tandemly repeated simple sequences. Lastly,
      several restriction length polymorphisms were identified and mapped within a 1 kb
      region located immediately upstream from the JH cluster. This finding suggests
      that polymorphisms within the IgH locus should be useful in the analyses of
      channel catfish populations. These combined studies provide further evidence that
      the genomic organization of heavy chain genes in bony fish shares common
      organizational features with those known from higher vertebrates.

PMID- 1347401
TI  - [Monotherapy with antihypertensive drugs: can a choice be made?].

PMID- 1347402
TI  - Alterations in cortical muscarinic receptors following cholinotoxin (AF64A)
      lesion of the rat nucleus basalis magnocellularis.
AB  - Cortical choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), tryptophan
      hydroxylase (TPH), muscarinic receptors and sodium-dependent, high-affinity,
      choline uptake (SDHACU) sites were examined in the rat brain following unilateral
      stereotaxic injection of the cholinotoxin, AF64A, into the nucleus basalis
      magnocellularis (NBM). Injection of AF64A resulted in a significant loss of
      presynaptic cholinergic markers in the cortex without alteration in TH and TPH
      activity. The binding to SDHACU sites was reduced to background values in the NBM
      and increased in the central amygdala (Ce) and cortex. The increase in cortical
      [3H]QNB binding was the result of a change in muscarinic receptor number (BMAX)
      and not a change in receptor affinity (KD). Examination of muscarinic receptor
      subtypes demonstrated a reduction of M1 receptor binding in the cortex and NBM
      without any alteration in the Ce. Non-M1 binding was significantly increased in
      all the laminae of the cortex and in the Ce, but decreased in the NBM. These data
      suggest that there exists a population of M1 receptors on NBM projections to the
      cortex and that NBM projections influence a population of postsynaptic receptors
      in the cortex and Ce which are not of the M1 subtype.

PMID- 1347403
TI  - Persistent changes in behaviour and brain serotonin during ageing in rats
      subjected to infant nasal virus infection.
AB  - Suckling rats were infected intranasally with the temperature-sensitive mutant
      G41 strain of vesicular stomatitis virus. The rats survived but demonstrated
      lifelong learning deficits in the Morris maze and impaired exploratory behaviour
      in the open field test. When examined at 18 months of age they had a severe loss
      of neurons in the medial and dorsal raphe nuclei in the brain stem and reduced
      levels of serotonin and its metabolite 5-hydroxyindole acetic acid in the
      cerebral neocortex and hippocampus. The levels of noradrenaline, dopamine,
      homovanillic acid, 3,4-dihydroxyphenylacetic acid, choline acetyltransferase and
      glutamate decarboxylase were largely unaffected. The permanent disturbance in
      brain serotonin metabolism did not cause any histological changes in the cerebral
      cortex. Thus there were no neurofibrillary tangles or amyloid plaques as has been
      reported as a late effect of chemically induced lesion to the cholinergic system
      in the rat brain. It is concluded that the brain serotonergic system is
      especially vulnerable to an episode of virus attack along olfactory pathways and
      that the neurochemical and behavioural alterations caused by such an episode
      persist during a major part of the animal's life span.

PMID- 1347404
TI  - Quantitative evaluation of the autoinhibitory feedback of release of 5-HT in the
      caudate nucleus of the rabbit where an endogenous tone on alpha 2-adrenoceptors
      does not exist.
AB  - Slices of caudate nucleus of the rabbit were preincubated with [3H]serotonin [(
      3H]5-HT) in the presence of nomifensine, then superfused and twice stimulated
      electrically. The stimulation-evoked overflow of tritium, representing action
      potential-induced, exocytotic release of 5-HT, was inhibited concentration
      dependently by 5-HT receptor ligands, the potencies of which were compatible with
      the assumption of a 5-HT1D-like autoreceptor. The inhibitor of the uptake of 5
      HT, 6-nitroquipazine, markedly changed the shape of the concentration-response
      curve of the 5-HT autoreceptor agonist, 5-carboxamido-tryptamine (5-COHT). The
      maximum effects of the concentration-response curves of 5-COHT and of exogenous 5
      HT became more pronounced in the additional presence of the 5-HT autoreceptor
      antagonists, metitepin or metergoline. Nonlinear regression analysis of these
      curves was used to estimate the pKd-value of endogenous 5-HT and the 5-HT
      biophase concentration at the autoreceptor, in the absence and in the presence of
      6-nitroquipazine and in the additional presence of metitepin or metergoline. This
      revealed a highly operative autoinhibitory feedback, via a 5-HT1D type
      autoreceptor of release of 5-HT in tissue from the caudate nucleus. Also the
      inhibition by the alpha 2-adrenoceptor agonists, clonidine and UK-14,304, of
      release of 5-HT was concentration-dependent. There was neither an enhancement of
      release by rauwolscine, being a 5-HT autoreceptor agonist and alpha 2
      adrenoceptor antagonist, in the presence of metitepin, or by the alpha
      adrenoceptor antagonist, phentolamine (10(-6) M).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1347405
TI  - Dopamine D2 synthesis-modulating receptors are present in the striatum of the
      guinea pig.
AB  - Dopamine and selective agonists of D1 [(1-phenyl-2,3,4,5-tetrahydro-(1H)-3
      benzazepine-7,8-diol hydrochloride, SKF 38393] and D2 [(3-[2-[N-(3
      hydroxyphenylethyl)-N-propylamino]ethyl] phenol, RU 24926] receptors were
      examined as inhibitors of the activity of tyrosine hydroxylase in the striatum of
      the guinea pig. In soluble enzyme preparations, the agonists were weak inhibitors
      of the activity of tyrosine hydroxylase. However, the catechol-containing
      agonists dopamine (EC50 = 44.7 microM) and SKF 38393 (EC50 = 35.5 microM) were
      more potent than the non-catechol agonist RU 24926 (EC50 = 447 microM). All of
      the agonists were much more potent in synaptosome-rich preparations of guinea pig
      striatum, where stimulation of autoreceptors mediated inhibition of the enzyme
      (SKF 38393, D1, EC50 = 27 nM; RU 24926, D2, EC50 = 30 nM; dopamine, non
      selective, EC50 = 1.5 microM). The D1 antagonist, SCH 23390 [(R(+)-7-chloro-8
      hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3- benzazepine hydrochloride],
      did not significantly reduce the action of SKF 38393 or dopamine. Furthermore,
      the D2 antagonist, (-)-sulpiride, significantly antagonized the inhibitory
      activity of both RU 24926 and dopamine. Studies in synaptosome-rich preparations
      from the striatum of the rat showed that both SKF 38393 (EC50 = 398 nM) and RU
      24926 (EC50 = 58 nM) were also effective autoreceptor-mediated inhibitors of the
      activity of tyrosine hydroxylase in the rat. However, in the rat, SCH 23390 and (
      )-sulpiride were equally effective in attenuating the inhibitory actions of
      dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347406
TI  - Neuroleptics increase c-fos expression in the forebrain: contrasting effects of
      haloperidol and clozapine.
AB  - The mechanisms by which the atypical neuroleptic clozapine produces its
      therapeutic effects in the treatment of schizophrenia without causing the
      extrapyramidal side effects that are characteristic of most antipsychotic drugs
      remain unclear. Recently, a single injection of the typical antipsychotic
      haloperidol has been shown to increase c-fos expression in the striatum [Dragunow
      et al. (1990) Neuroscience 37, 287-294]. C-fos is a proto-oncogene that encodes a
      55,000 mol. wt phosphoprotein, Fos, which is thought to assist in the regulation
      of "target genes" containing an AP-1 binding site. Because a wide variety of
      physiological and pharmacological stimuli increase c-fos expression, it has been
      proposed that Fos immunohistochemistry might be useful in mapping functional
      pathways in the central nervous system. The present experiments examined some
      potential neuroanatomical differences in the actions of clozapine and haloperidol
      by comparing their effects on c-fos expression in the medial prefrontal cortex,
      nucleus accumbens, striatum and lateral septum. The effects of the selective
      dopamine receptor antagonists SCH 23390 (D1) and raclopride (D2) were also
      examined. Haloperidol (0.5, 1 mg/kg) and raclopride (1, 2 mg/kg) produced large
      increases in the number of Fos-containing neurons in the striatum and nucleus
      accumbens. SCH 23390 (0.5, 1 mg/kg) reduced the number of Fos-positive neurons in
      the nucleus accumbens and striatum, and had no effect in the other regions.
      Neither haloperidol nor raclopride increased the number of Fos-positive neurons
      in the medial prefrontal cortex. Haloperidol, but not raclopride, produced a
      modest increase in c-fos expression in the lateral septal nucleus. Clozapine (10,
      20 mg/kg) was without effect in the striatum; however, it significantly increased
      the number of Fos-positive neurons in the nucleus accumbens, medial prefrontal
      cortex and lateral septal nucleus. Destruction of mesotelencephalic dopaminergic
      neurons with 6-hydroxydopamine abolished the increase in Fos expression in the
      nucleus accumbens and striatum produced by haloperidol and raclopride, and also
      blocked the clozapine-induced increase in the nucleus accumbens. However, the
      inductive effects of clozapine and haloperidol on c-fos expression in the lateral
      septal nucleus and of clozapine in the medial prefrontal cortex were not affected
      by the 6-hydroxydopamine lesions. These results suggest that clozapine's unique
      therapeutic profile may be related to its failure to induce Fos in the striatum
      as well as its idiosyncratic actions in the lateral septum and medial prefrontal
      cortex. The effects of clozapine in these latter regions do not appear to be
      mediated by dopaminergic mechanisms.

PMID- 1347407
TI  - Cortical stimulation induces fos expression in striatal neurons.
AB  - Electrical stimulation of a broad area of the frontoparietal cortex in the rat
      brain induces immunocytochemically detectable Fos in striatal neurons normally
      devoid of the protein. The vividness of labeling within striatal neurons was
      maximal at 0.5 h after the cessation of a 15-min-long stimulation period and
      became weaker by 3 h. Although Fos-reactive neurons were widely distributed in
      the striata of both hemispheres in an uneven pattern, those on the stimulated
      side were more numerous and more darkly stained. At no time-point were labeled
      neurons found in the globus pallidus, entopeduncular nucleus or substantia nigra.
      Destruction of the nigrostriatal dopamine projection with 6-hydroxydopamine did
      not induce Fos production and failed to prevent the induction of Fos by cortical
      stimulation. That many of the Fos-positive neurons project to the substantia
      nigra was confirmed by retrograde labeling with Fluoro-Gold. The data suggest
      that corticostriatal excitatory transmission may directly influence the genomic
      activity of striatal neurons by way of Fos.

PMID- 1347408
TI  - Effects of aging on signal transmission and transduction systems in the gerbil
      brain: morphological and autoradiographic study.
AB  - The Mongolian gerbil was used as a model of aging because of its relatively short
      lifespan, genetic homogeneity and the fact that data had been collected
      previously. Furthermore, gerbils have been widely used in biomedical
      investigations of stroke and epilepsy. Age-related differences in signal
      transmission and transduction systems were investigated in brains of three-, 11-
      and 21-month-old gerbils by morphological and in vitro receptor autoradiographic
      studies. Morphometric analysis revealed a decreased number of neurons in layer
      III of the occipital cortex and also a decrease in cerebellar Purkinje cells in
      21-month-old animals. However, no statistical differences were observed in the
      hippocampal formation, the dorsolateral striatum and layer III of the frontal
      cortex. Autoradiography was used to map muscarinic cholinergic (labeled with
      [3H]quinuclidinyl benzilate), serotonin2 ([3H]spiperone), dopamine D2
      ([3H]spiperone), adenosine A1 ([3H]cyclohexyladenosine), GABAA ([3H]muscimol),
      naloxone ([3H]naloxone), protein kinase C ([3H]phorbol 12,13-dibutyrate),
      adenylate cyclase ([3H]forskolin), cyclic AMP ([3H]cyclic AMP) and L-type Ca2+
      channels ([3H]PN200-110). Muscarinic cholinergic receptor and protein kinase C,
      cyclic AMP and L-type Ca2+ channels were significantly decreased in the cerebral
      cortex and/or in the CA1 subfield of the hippocampus in the 21-month-old group.
      Muscarinic cholinergic receptor and L-type Ca2+ channel binding sites were
      significantly reduced in the dentate gyrus. In contrast, protein kinase C was
      increased in this area in the 21-month-old group. Also, naloxone binding sites
      were increased in the CA3 subfield, hilus, dentate gyrus and molecular layer of
      the cerebellum in the 11- and 21-month-old groups. Muscarinic cholinergic,
      serotonin2 and dopamine D2 receptors and adenylate cyclase were significantly
      decreased in the striatum. On the other hand, adenosine A1 and GABAA receptors
      remained unchanged in the 21-month-old group. Although age-related
      histopathological abnormalities were only observed in the occipital cortex and in
      the cerebellum, alterations of signal transmission and transduction systems were
      noticed in all areas examined (e.g. cerebral cortex, CA1 subfield, dentate gyrus
      and striatum). These data indicate that changes in these receptors and binding
      sites may be related to dysfunction of learning and memory and to the loss of
      motor function. The aged gerbil model is a good system for studying aging and is
      of value for simulating aging after epilepsy and stroke.

PMID- 1347409
TI  - Detecting changes in neuronal activities induced by N-methyl-D-aspartate receptor
      blockade using non-linear dynamics techniques.
AB  - The dynamics of N-methyl-D-aspartate receptor blockade-induced transitions
      between two types of intracellularly recorded spontaneous membrane potential
      oscillation from cat thalamic neurons have been studied using non-linear dynamics
      techniques. We report that, as previously predicted by theoretical studies, the
      number of degrees of freedom of these oscillations (the minimal number of
      independent variables governing the activity) is small, i.e. they are low
      dimensional. The N-methyl-D-aspartate receptor antagonists DL-2-amino-5-phosphono
      valeric acid and ketamine, which transformed one type of oscillation into
      another, decreased the calculated dimension. DL-2-Amino-5-phosphono-valeric acid
      had no effect on the dimension when Mg2+ was present in the perfusion medium. The
      decrease in dimension was gradual and its time-course had a sigmoidal shape. It
      is suggested that the application of the machinery of dynamical systems theory
      might help to detect and monitor drug-induced membrane potential state
      transitions and to identify the factors underlying membrane potential
      oscillations.

PMID- 1347411
TI  - Disturbance of fluid homeostasis leads to temporally and anatomically distinct
      responses in neuropeptide and tyrosine hydroxylase mRNA levels in the
      paraventricular and supraoptic nuclei of the rat.
AB  - The response of six mRNAs (for prepro-corticotropin-releasing hormone, prepro
      enkephalin, prepro-vasoactive intestinal polypeptide/peptide histidine
      isoleucine, prepro-neurotensin/neuromedin N, prepro-cholecystokinin, and prepro
      tyrosine hydroxylase) was measured in the hypothalamic paraventricular and
      supraoptic nuclei after increasing periods of osmotic stimulation caused by the
      replacement of regular drinking water with hypertonic saline (up to five days) or
      by forced dehydration (up to three days). In addition, hematocrits and
      concentrations of corticosterone were determined after the different periods of
      osmotic stimulation and correlated with the effects on the content of the various
      mRNAs. The temporal response of the mRNAs within the paraventricular and
      supraoptic nuclei to osmotic stimulation was different within the three
      compartments of these nuclei. First, in response to overnight osmotic
      stimulation, magnocellular neurosecretory neurons increased their mRNA content
      for two molecules (prepro-corticotropin-releasing hormone and tyrosine
      hydroxylase). As the stimulus was maintained over the next two to four days,
      these cells accumulated the mRNAs for at least three other peptides
      (cholecystokinin, vasoactive intestinal polypeptide/peptide histidine isoleucine
      and enkephalin). Second, the response of peptide-coding mRNAs in parvicellular
      neurosecretory neurons of the paraventricular nucleus appeared to be slower; no
      changes could be measured after overnight stimulation. However, after a further
      two- to four-days of continued osmotic stimulation, the content of the mRNA
      coding for corticotropin-releasing hormone markedly decreased while that for
      cholecystokinin increased. No change in the content of the mRNAs coding for
      prepro-vasoactive intestinal polypeptide/peptide histidine isoleucine,
      enkephalin, and prepro-neurotensin/neuromedin N could be seen at any time after
      osmotic stimulation in parvicellular neurosecretory neurons. Third, increases in
      the content of mRNA coding for corticotropin-releasing hormone in the
      parvicellular neurons that provide descending projections from the
      paraventricular nucleus could only be detected after longer periods of osmotic
      stimulation. The effect of osmotic stimulation on plasma corticosterone
      concentrations was quickly apparent; plasma corticosterone concentrations were
      significantly elevated on the first morning after the beginning of salt-loading,
      and demonstrated the rapid effects of osmotic stimulation on the mechanisms
      controlling corticosterone release. These results show that the synthetic
      capability of cells in all three compartments of the paraventricular and
      supraoptic nuclei are modified by osmotic stimulation over different time scales,
      thereby allowing differential modulation of the neuroendocrine, autonomic, and
      behavioral components of the animal's response to disturbances in fluid
      homeostasis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1347410
TI  - Neuroactive amino acids in organotypic slice cultures of the rat hippocampus: an
      immunocytochemical study of the distribution of GABA, glutamate, glutamine and
      taurine.
AB  - Antisera raised against protein-glutaraldehyde-amino acid conjugates were used to
      study the light and electron microscopic distribution of GABA, glutamate,
      glutamine and taurine in organotypic slice cultures of rat hippocampi. In the
      stratum oriens and radiatum, glutamate-like immunoreactivity was particularly
      concentrated in nerve endings establishing asymmetric junctions with dendritic
      spines. Mossy fiber terminals in CA3 and the dentate hilus were also strongly
      labeled. A quantitative immunogold analysis of the glutamate-immunolabelled
      profiles showed a pattern that was highly reminiscent of that previously observed
      in perfusion-fixed hippocampi, including a correspondingly sparse labeling of
      glial processes and of presynaptic elements in symmetric synapses. GABA-like
      immunoreactivity was localized predominantly in interneurons and in presynaptic
      terminals contacting dendritic shafts and neuronal cell bodies, while
      immunoreactivities for glutamine and taurine were found mainly in astroglial
      cells and pyramidal cells, respectively. Our data indicate that the major
      intrinsic fiber systems of the cultured hippocampi have retained their normal
      transmitter phenotypes.

PMID- 1347412
TI  - Intracellular redistribution of neuropeptides and secretory proteins during
      differentiation of neuronal cell lines.
AB  - We have demonstrated that the mouse neuroblastoma N18Tg2 cell line and several
      clones of hybrid ND cells (ND7, ND9 and ND21), derived from the fusion of
      neonatal rat sensory neurons with that neuroblastoma, show immunostaining to
      protein gene product 9.5, neuropeptide Y, C-flanking peptide of neuropeptide Y,
      tyrosine hydroxylase and chromogranins. Synaptophysin could only be detected in
      ND cells. Immunoreactivities to substance P, calcitonin gene-related peptide,
      galanin and somatostatin could not be detected in any of these cell lines. After
      three days of incubation in a differentiation medium, cell processes of various
      lengths were observed both in neuroblastoma and ND cell cultures. In ND7 cells
      there was also a redistribution of neuropeptide Y and its C-flanking peptide to
      the tips of cell processes. The differentiation of cell processes was also
      accompanied by the appearance of immunostaining to rat chromogranins in their
      tips. In contrast, synaptophysin expression was found mainly in cell bodies.
      Neuropeptide Y, its C-flanking peptide and chromogranins have been associated
      with secretory granules, whereas synaptophysin is a marker for small synaptic
      like vesicles. Therefore, our morphological findings further support and expand
      the view that these markers are primarily associated with different subcellular
      structures. Moreover, they indicate that the regulated secretory pathway
      associated with chromogranins is segregated into nerve processes at an early
      stage of differentiation, when the synaptophysin-associated pathway is not yet
      mature. ND7 cells thus provide a useful model system for studying changes in the
      distribution of neuropeptides, cytoskeletal elements and proteins associated with
      cell secretion during neuronal differentiation.

PMID- 1347413
TI  - Dopaminergic transplants normalize amphetamine- and apomorphine-induced Fos
      expression in the 6-hydroxydopamine-lesioned striatum.
AB  - Dopamine receptor-mediated Fos protein expression in the striatum has been used
      to monitor dopamine receptor activation at the cellular level after dopaminergic
      denervation and reinnervation by fetal nigral transplants. The pattern of
      striatal Fos expression after systemic administration of either the dopamine
      receptor agonist, apomorphine, or the dopamine-releasing agent, amphetamine, was
      studied in rats which had received cell suspension grafts of fetal ventral
      mesencephalic neurons into the striatum after a complete 6-hydroxydopamine lesion
      of mesostriatal dopaminergic projection. Grafted animals, and normal and lesioned
      controls were killed 2 h after administration of either D-amphetamine (5 mg/kg,
      i.p.) or apomorphine (0.25 mg/kg, s.c.). Fos protein was detected
      immunohistochemically, and the density of Fos-immunoreactive cell nuclei was
      measured in 12 selected areas of caudate-putamen, nucleus accumbens and globus
      pallidus by computerized image analysis. Consistent with previous studies,
      amphetamine induced high Fos expression in the medial and dorsal parts of the
      intact caudate-putamen and significantly lower expression in the denervated
      caudate-putamen. A significant difference between lesioned and intact striata was
      present also in globus pallidus, but not in nucleus accumbens. In grafted rats,
      amphetamine-induced Fos activation was restored to normal or supranormal levels
      in the anterior and central caudate-putamen (i.e. close to the graft deposits),
      whereas in the tail of caudate-putamen Fos expression was significantly lower
      than normal. The side-to-side difference in globus pallidus seen in lesioned rats
      was no longer present in the grafted animals. Apomorphine led to high Fos
      activation throughout the dopamine-depleted caudate-putamen, whereas only very
      few immunopositive cells were observed in the intact caudate-putamen. Also in
      globus pallidus and nucleus accumbens, a significantly higher number of Fos
      immunoreactive cells was detected on the denervated side. In the grafted rats,
      apomorphine-induced Fos activation was similar to normal in all striatal areas
      sampled, as well as in the globus pallidus. The graft-induced effect extended
      over a considerably larger area than that covered by the graft-derived tyrosine
      hydroxylase-immunoreactive innervation. These findings indicate that fetal
      ventral mesencephalic transplants normalize dopamine receptor-mediated function
      in the 6-hydroxydopamine-lesioned caudate-putamen and nucleus accumbens, as well
      as in a primary target of the striatal output neurons, the globus pallidus. The
      results support the idea that dopamine released from the grafted neurons, both
      under baseline conditions and after amphetamine administration, exerts functional
      effects over a larger volume of the striatum than that reached by the graft
      derived fibers.

PMID- 1347414
TI  - CPP, an NMDA-receptor antagonist, blocks 4-aminopyridine-induced spreading
      depression episodes but not epileptiform activity in immature rat hippocampal
      slices.
AB  - Spontaneous episodes of spreading depression (SD) were observed in the CA3
      subfield of immature or young (2-30 days postnatally) hippocampal slices perfused
      with medium containing 4-aminopyridine (4-AP, 50 microM). SD appeared in 34% of
      the hippocampal slices examined and was more frequently observed in slices
      obtained from 11 to 20-day-old animals. SD studied with extracellular field
      potential recordings consisted of large amplitude (18.7 +/- 1.1 mV, mean +/-
      S.E.M.) negative DC shifts that lasted 30-250 s. Unlike the epileptiform activity
      that was concomitantly seen during 4-AP application, SD was blocked by the NMDA
      receptor antagonist 3-((RS)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid
      (CPP, 2-10 microM). In contrast, 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX, 5
      microM), a non-NMDA-type receptor antagonist, blocked the epileptiform activity
      but only increased the interval between SD episodes. These results demonstrate
      that immature hippocampal tissue is susceptible to SD episodes, when perfused
      with 4-AP-containing medium, and that the occurrence of these episodes presumably
      depends on the activation of the NMDA receptor. In addition these findings
      indicate that SD shows a sensitivity to excitatory amino acid receptor
      antagonists that differs from that of the epileptiform activity recorded
      simultaneously.

PMID- 1347415
TI  - Induction of stable long-term potentiation in the presence of the protein kinase
      C antagonist staurosporine.
AB  - We have studied the effects of staurosporine, an antagonist of the catalytic
      subunit of protein kinase C, on the mechanisms of long-term potentiation (LTP) in
      rat hippocampal slices maintained in vitro. Application of staurosporine did not
      affect pre-established LTP, but resulted in a decaying potentiation when high
      frequency stimulation was delivered in its presence. However, coactivation of two
      inputs to the same group of CA1 neurons during high frequency stimulation
      transformed the decaying potentiation into stable LTP. Staurosporine also reduced
      the NMDA receptor-mediated component of synaptic responses to burst stimulation.
      It is concluded that the PKC antagonist interferes with LTP induction, but not
      expression mechanisms.

PMID- 1347416
TI  - Melatonin synthesis in chicken retina: effect of kainic acid-induced lesions on
      the diurnal rhythm and D2-dopamine receptor-mediated regulation of serotonin N
      acetyltransferase activity.
AB  - The effect of kainic acid (KA)-induced lesions of retinal neurons on regulation
      of serotonin N-acetyltransferase (NAT) activity in chicken retina was
      investigated. Although NAT activity was higher in KA-lesioned retinas than in
      controls, the pattern of diurnal variation of enzyme activity throughout 36 h of
      constant darkness was similar for both tissues. Quinpirole, a selective D2
      dopamine receptor agonist, inhibited the nocturnal increase of NAT activity in
      both control and KA-treated retinas. Quinpirole was significantly more potent in
      KA-treated retinas than in controls; the ED50 value for quinpirole was 3 times
      lower in KA-treated retinas than in control tissues. KA treatment markedly
      reduced retinal levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid
      (DOPAC). We conclude that: (1) NAT activity in retina is localized primarily to
      KA-insensitive cells, presumably photoreceptors; (2) KA-sensitive inner retinal
      neurons are not essential to the maintenance of the circadian rhythm of NAT
      activity; and (3) KA-induced lesions of retinal cells result in supersensitivity
      of D2-dopamine receptors regulating NAT activity in a mechanism that involves
      adaptive changes following a decline in retinal dopamine neurotransmission.

PMID- 1347417
TI  - Correlations between c-erb beta-2 oncogene amplification and the expression of
      its mRNA and protein in human breast carcinomas.
AB  - Nineteen human breast tumours were analysed for c-erb beta-2 gene amplification,
      the over-expression of its mRNA and the production of its protein residue by
      southern blot, northern blot and western blot technique respectively. Protein
      expression was also assessed by immunohistochemistry on paraffin sections, c-erb
      beta-2 gene amplification was found in 6 of 19 (31%) tumours. Over-expression of
      c-erb beta-2 mRNA was found in 7 of 19 (37%) tumours. Expression of the 185 kd c
      erb beta-2 protein product was detected in 3 of 19 (16%) tumours by western
      blotting and in 5 of 19 (26%) by immunohistochemistry. In only 4 tumours with an
      amplified c-erb beta-2 gene was there a clear association between all three
      parameters. In view of the conflicting reports in the literature concerning c-erb
      beta-2 gene amplification or protein over-expression (assessed by western blot or
      immunohistochemistry) and prognosis of breast cancer, studies in which these
      parameters are correlated individually with prognosis in the same group of
      patients are needed.

PMID- 1347418
TI  - Selective cleavage of closely-related mRNAs by synthetic ribozymes.
AB  - In Phaseolus vulgaris L. (French bean) glutamine synthetase (GS) is encoded by
      four closely-related genes termed gln-alpha, gln-beta, gln-gamma and gln-delta.
      We have constructed and characterised in vitro a number of hammerhead ribozymes
      designed to cleave individual RNAs encoded by these genes. The three ribozymes,
      termed J1, J2 and J3, were targeted to cleave RNA at the start of the gamma and
      beta, and the middle of the gamma, GS open reading frames respectively. All three
      ribozymes successfully discriminated between the four (alpha, beta, gamma and
      delta) highly homologous sequences, even though the targeted sites of cleavage
      shared up to 18 out of 22 identical bases with other gene family members. The
      ribozyme-mediated cleavage reactions were Mg2+ dependent and enhanced at higher
      temperatures, although the J1 ribozyme retained considerable activity at
      physiological temperatures. Both J1 and J2 demonstrated a time-dependent cleavage
      of their targeted GS RNAs, although these two ribozymes differed markedly in
      their ability to cleave multiple substrate molecules. The rate of cleavage by J1
      was found to be reduced in the presence of related GS RNAs and by total leaf
      poly(A) RNAs. The implications of these results for ribozyme activity in vivo are
      discussed.

PMID- 1347419
TI  - Rapid screening of cloned DNA fragments for specific mutations.

PMID- 1347420
TI  - Detection of the XmnI RFLP at the human PAH locus by PCR.

PMID- 1347422
TI  - Harboring our resources. Caring for our tomorrow. Oncology Nursing Society 17th
      Annual Congress. San Diego, May 13-16, 1992. Abstracts.

PMID- 1347421
TI  - A new TaqI polymorphism in the p53 gene.

PMID- 1347423
TI  - C-erbB-2 protein and neuroendocrine expression in intraductal carcinomas of the
      breast.
AB  - A total of 52 intraductal carcinomas were classified according to nuclear size
      and histologic subtype and immunostained for neuron-specific enolase (NSE) and c
      erbB-2 oncoprotein. Eleven out of 13 cases of the large cell comedo variant of
      intraductal carcinoma exhibited strong c-erbB-2 protein immunoreactivity, while
      only one was NSE positive. Nineteen out of 23 intraductal carcinomas of small
      cell type exhibited NSE immunoreactivity. None of these was c-erbB-2 protein
      positive. Some 72% of NSE positive cases were also immunoreactive for other
      neuroendocrine screening markers and/or hormones. We conclude that there is an
      inverse relationship between NSE immunoreactivity and c-erbB-2 protein expression
      in intraductal carcinomas.

PMID- 1347424
TI  - DNA ploidy, proliferation, and neu-oncogene protein overexpression in breast
      carcinoma.
AB  - DNA content, proliferative activity (Ki-67 immuno-staining and S-phase fraction
      by flow cytometry), and neu-oncogene overexpression were studied in 135 patients
      with invasive breast carcinoma. Image analysis and flow cytometry of fresh tumors
      showed good correlation between the two methods and yielded 39% diploid tumors
      and 61% aneuploid tumors. Aneuploidy, including tetraploidy, was significantly
      related to the loss of estrogen (p = 0.0002) and progesterone (p = 0.03)
      receptors, high histologic (p = 0.014) and nuclear (p less than 0.0001) grades,
      and mitotic rate (p = 0.0001). Immunohistochemical evaluation of proliferation by
      staining with Ki-67 monoclonal antibody and of neu-oncogene protein
      overexpression was performed in fresh frozen tissue from 83 tumors. The Ki-67
      score, quantitated by the CAS-200 image analyzer, correlated only moderately with
      S-phase fraction obtained by flow cytometry by linear regression analysis (r =
      0.39, p less than 0.001). However, both of these proliferation markers correlated
      strongly with the mitotic rate (p less than 0.0001). Aneuploid and tetraploid
      tumors demonstrated higher Ki-67 scores and S-phase fractions than diploid
      tumors. Neu-oncogene protein overexpression was seen in 24 tumors (29%) overall
      and was much higher in aneuploid tumors (38%) and tetraploid tumors (50%) than in
      diploid tumors (7%). However, the concentration of neu-oncogene protein positive
      tumors in the tetraploid region reported by others was not observed. Neu-oncogene
      protein overexpression was also associated with higher Ki-67 scores (p = 0.016)
      and S-phase fractions (p = 0.037).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347425
TI  - Human chromosome 11 contains two different growth suppressor genes for embryonal
      rhabdomyosarcoma.
AB  - The identification of acquired homozygosity in human cancers implies locations of
      tumor suppressor genes without providing functional evidence. The localization of
      a defect in embryonal rhabdomyosarcomas to chromosomal region 11p15 provides one
      such example. In this report, we show that transfer of a normal human chromosome
      11 into an embryonal rhabdomyosarcoma cell line elicited a dramatic loss of the
      proliferative capacity of the transferrants. Indeed, the majority of the viable
      microcell hybrids had either eliminated genetic information on the short arm of
      the transferred chromosome 11 or increased the copy number of the
      rhabdomyosarcoma-derived chromosomes 11. Cells that possessed only the long arm
      of chromosome 11 also demonstrated a decreased growth rate. In contrast, all
      microcell hybrids retained the ability to form tumors upon inoculation into
      animals. These functional data support molecular studies indicating loss of
      genetic information on chromosome 11p15 during the development of embryonal
      rhabdomyosarcoma. In addition, our studies demonstrate the existence of a second
      gene on the long arm, previously unrecognized by molecular analyses, which
      negatively regulates the growth of embryonal rhabdomyosarcoma cell lines.

PMID- 1347426
TI  - The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]:
      serotonin transporters are targets for MDMA-induced serotonin release.
AB  - MDMA ("ecstasy") has been widely reported as a drug of abuse and as a neurotoxin.
      This report describes the mechanism of MDMA action at serotonin transporters from
      plasma membranes and secretory vesicles. MDMA stimulates serotonin efflux from
      both types of membrane vesicle. In plasma membrane vesicles isolated from human
      platelets, MDMA inhibits serotonin transport and [3H]imipramine binding by direct
      interaction with the Na(+)-dependent serotonin transporter. MDMA stimulates
      radiolabel efflux from plasma membrane vesicles preloaded with [3H]serotonin in a
      stereo-specific, Na(+)-dependent, and imipramine-sensitive manner characteristic
      of transporter-mediated exchange. In membrane vesicles isolated from bovine
      adrenal chromaffin granules, which contain the vesicular biogenic amine
      transporter, MDMA inhibits ATP-dependent [3H]serotonin accumulation and
      stimulates efflux of previously accumulated [3H]serotonin. Stimulation of
      vesicular [3H]serotonin efflux is due to dissipation of the transmembrane pH
      difference generated by ATP hydrolysis and to direct interaction with the
      vesicular amine transporter.

PMID- 1347427
TI  - Screening for receptor ligands using large libraries of peptides linked to the C
      terminus of the lac repressor.
AB  - We have constructed a large library of random peptides fused to the C terminus of
      the lac repressor. The DNA binding activity of the repressor protein physically
      links the peptides to the plasmid encoding them by binding to lac operator
      sequences on the plasmid. This linkage allows efficient enrichment for specific
      peptide ligands in the random population of peptides by affinity purification of
      the peptide-repressor-plasmid complexes with an immobilized receptor. After
      transformation of Escherichia coli with recovered plasmids, the library can be
      amplified for additional rounds of affinity enrichment or specific plasmids can
      be sequenced to determine the primary structure of the peptides. We used a
      monoclonal antibody specific for the peptide dynorphin B as a model receptor to
      screen a random dodecamer library. After only two rounds of enrichment, the
      majority of the plasmids in the selected population encoded fusion peptides that
      bound specifically to the antibody. These peptides contain a consensus sequence
      similar to a segment of dynorphin B (RQFKVV). This technique should be useful to
      find peptide ligands for a variety of biological receptors.

PMID- 1347430
TI  - [Psychobiology of fear].
AB  - Fear is an affective experience and a normal psychobiologic reaction preparing
      the organism for defense or avoidance of threats. It is only abnormal when
      extent, expression and duration do not match the real danger. Three processes are
      elementary components of fear: 1. the perception of a signal for threat, 2.
      expectation, defined as inner mobilisation and augmented directional attention,
      3. feeling arising from impending loss of control over the inner and outer
      milieu. Mutual dependence and interference between the three processes are often
      the basis for vicious circles in pathologic states of fear. Various aspects of
      fear, mainly of the anticipated fear can be explained by conditioned behaviour, a
      fact of significance not at last for rational psychotherapy. The form of
      expression and the extent of a reaction to fear is according to the hypothesis of
      Gray regulated by a complex functional central nervous system. The primary role
      of the latter consists in an inhibition of the actual behaviour in order to allow
      for alternative reactions adapted to the new circumstances. Intensity and quality
      of alarming signals ultimately determining the outcome of the reaction are
      mediated by neurotransmitters. These assure the correct transmission within the
      neuronal network and regulate the extent of activation off all neuronal cells.
      Three neurotransmitters are assumed to have an essential role in fear:
      norepinephrine, serotonin and gamma-amino-butyric-acid (GABA). The action of GABA
      has been documented best so far. An increase of inhibitory GABA-effects is also
      the main mechanism of action of benzodiazepines and benzodiazepine-like
      anxiolytics.

PMID- 1347429
TI  - Human T-cell lymphotropic virus (HTLV)-related endogenous sequence, HRES-1,
      encodes a 28-kDa protein: a possible autoantigen for HTLV-I gag-reactive
      autoantibodies.
AB  - The presence of a human T-cell lymphotropic virus (HTLV)-related endogenous
      sequence, HRES-1, in the human genome has been documented. The HRES-1 genomic
      locus is transcriptionally active and contains open reading frames. Antibodies
      232 and 233, specific for synthetic peptides pep14-24 and pep117-127,
      corresponding to two nonoverlapping HTLV-related regions in the longer open
      reading frame of HRES-1, recognize an identical 28-kDa protein in H9 human T
      cells. Thus, HRES-1 is a human endogenous retroviral sequence capable of protein
      expression. HRES-1/p28 is localized to the cytoplasm and nuclear bodies. While
      HTLV-I-specific antibodies react with HRES-1 peptides, antibody 233 cross-reacts
      with HTLV-I gag p24 protein. Three consecutive highly charged amino acid
      residues, Arg-Arg-Glu, present in both HRES-1 pep117-127 and HTLV-I gag p24 are
      likely to be the core of cross-reactive epitopes. The prevalence of antibodies to
      HRES-1 peptides pep14-24 and pep117-127 was determined in 65 normal blood donors
      and 146 patients with immunological disorders. Sera of patients with multiple
      sclerosis (19 out of 65, 29%), progressive systemic sclerosis (4 out of 17, 23%),
      systemic lupus erythematosus (4 out of 19, 21%), and Sjogren syndrome (2 out of
      19, 10%) contained significantly higher HRES-1 peptide binding activity than sera
      of normal donors. Sera of patients with AIDS showed no specific binding to HRES-1
      peptides. Nine of 30 HRES-1-seropositive patients showed immunoreactivity to HTLV
      I gag p24. The data indicate that HRES-1/p28 may serve as an autoantigen
      eliciting autoantibodies cross-reactive with HTLV-I gag antigens.

PMID- 1347428
TI  - Distinct hypermethylation patterns occur at altered chromosome loci in human lung
      and colon cancer.
AB  - Regional increases in DNA methylation occur in normally unmethylated cytosine
      rich areas in neoplastic cells. These changes could potentially alter chromatin
      structure to inactivate gene transcription or generate DNA instability. We now
      show that, in human lung and colon cancer DNA, hypermethylation of such a region
      consistently occurs on chromosome 17p in an area that is frequently reduced to
      homozygosity in both tumor types. Over the progression stages of colon neoplasia,
      this methylation change increases in extent and precedes the allelic losses on
      17p that are characteristic of colon carcinomas. We also show on chromosome 3p
      that regional hypermethylation may nonrandomly accompany chromosome changes in
      human neoplasia. Increased methylation is consistent in small-cell lung carcinoma
      DNA at two 3p loci that are constantly reduced to homozygosity in this tumor, but
      it is not seen in colon cancer DNA, in which these loci are infrequently
      structurally altered.

PMID- 1347431
TI  - Current issues in the management of Zollinger-Ellison syndrome.

PMID- 1347432
TI  - Analysis of HLA class II allogenotyping in Australian aborigines and Papua New
      Guinea populations.
AB  - Human leukocyte antigen (HLA) class II allogenotyping has been applied to
      investigate the polymorphism of the DRB, DQB1, DQB2, DQA1, and DQA2 genes in
      Aborigines from the East Coast of Australia and in Melanesians from the Papua New
      Guinea North-East Coast and Highlands. Three new DR/DQ arrangements were
      observed, DRw14/DQB1-2b/DQA1-1a and DRw5Nauru/DQB1-3a/DQA1-2 (n Australian
      Aborigines), and DRw5Nauru/DQB1-1a/DQA1-1b (in Madang). DQA2 and DQB2
      allogenotyping with TaqI and PstI digested genomic DNA revealed little
      polymorphism among the Papua New Guineans, with DQA2-Xa1 and DQB2-Xb1 the most
      common alleles in all the groups. However, the presence of DQA2-Xa2 in Papuans
      and Australian Aborigines reflects the degree of admixture with Caucasoids while
      the DQA2-Xa4 allele in Madang is probably a marker of Mongoloid origin.

PMID- 1347433
TI  - Questions about inhaled beta 2-adrenoceptor agonists in asthma.
AB  - The safety of the most widely prescribed antiasthma drugs, beta 2-adrenoceptor
      agonists, has recently been questioned. Issues such as their suitability for long
      term and regular prophylactic use are addressed in this Comment article by Peter
      Barnes and Fan Chung, who examine the possibility that the beta 2-agonists
      themselves contribute to worsening symptoms in asthma patients, thus setting up a
      vicious circle with greater use of the drugs. They conclude that it would be
      prudent to restrict the use of beta 2-agonists in asthma to on-demand immediate
      symptom control.

PMID- 1347434
TI  - Distemper encephalitis in pups after vaccination of the dam.
AB  - A five-year-old labrador bitch which had whelped 10 pups three days previously
      was given booster vaccination against distemper, adenovirus, parvovirus,
      parainfluenzavirus and leptospirosis. Eighteen days later, signs of central
      nervous system disease developed in some of the pups, five of which were
      ultimately euthanased. The cause of the nervous disease was found to be canine
      distemper, and serological studies showed that the infection was limited to some
      members of the litter, suggesting that the vaccinal rather than a field virus was
      more likely to have been responsible.

PMID- 1347435
TI  - Use of medetomidine-fentanyl-fluanisone combinations in the badger.

PMID- 1347436
TI  - Novel antiepileptic drugs. Relations with neurotransmitter mechanisms underlying
      frontal epilepsies.

PMID- 1347437
TI  - Nonsedating antihistamines: pharmacology, clinical efficacy and adverse effects.
AB  - Antihistamines are effective therapy for histamine-mediated conditions, including
      seasonal and perennial allergic rhinitis and chronic urticaria. Until recently,
      all antihistamines produced some degree of drowsiness, as well as anticholinergic
      side effects. Several nonsedating antihistamines have been developed. Two of
      these antihistamines--terfenadine and astemizole--are commercially available. The
      lack of central nervous system effects is attributed to the inability of these
      drugs to penetrate the blood-brain barrier. They also have no appreciable binding
      to cholinergic receptors. Clinical trials have demonstrated that the newer agents
      are as effective as classic antihistamines and that they have no greater
      incidence of central nervous system or anticholinergic side effects than placebo.

PMID- 1347438
TI  - A Symposium: The Ischemic Myocardium: Strategies for Preservation and Protection,
      March 6, 1992.

PMID- 1347439
TI  - Brain damage from pertussis immunization. A Canadian neurologist's perspective.
AB  - Uncontrolled case series noting an association between diphtheria, tetanus, and
      pertussis vaccine (DTP) immunization and brain damage have lead to widespread
      reduction in immunization, epidemics of pertussis and litigation. A judge,
      hearing the only Canadian court case, concluded there is no evidence that DTP
      induced brain injury. It is difficult to develop a cogent biologic hypothesis for
      the mechanism of DTP-induced brain injury, especially when the postulated
      clinical syndrome is variable without a characteristic neuropathologic pattern.
      Timed observational, case-controlled, and prospective cohort studies have not
      shown evidence of brain damage from pertussis vaccine. This suggests that the
      cause(s) of brain injury recorded in case series was other than DTP immunization.
      Any relationship is likely a temporal coincidence because DTP is administered
      several times in infancy. A vigorous effort is required to dispel the myth of DTP
      induced brain damage.

PMID- 1347440
TI  - Strategies in endovascular interventions. Proceedings of the International
      Congress V--Part 2. Scottsdale, Arizona, February 12-16, 1992. Abstracts.

PMID- 1347441
TI  - Congress of Nursing Practice meets.

PMID- 1347442
TI  - Relationship between dideoxyinosine exposure, CD4 counts, and p24 antigen levels
      in human immunodeficiency virus infection. A phase I trial.
AB  - OBJECTIVE: To determine the relation between exposure to dideoxyinosine (ddl) and
      increased CD4 cell counts and suppression of serum p24 antigen in patients
      infected with the human immunodeficiency virus (HIV). DESIGN: Open-label, phase I
      study. SETTING: Two university hospitals. Patients were studied in both inpatient
      and outpatient settings. PATIENTS: Of 36 HIV-infected patients enrolled, 18 had
      adequate pharmacokinetic information for analysis. INTERVENTION: Dideoxyinosine
      was administered intravenously every 12 hours for 2 weeks. Patients were switched
      to oral administration at twice the intravenous dose. Pharmacokinetic profiles
      were obtained twice during each period. A 40-fold range of dose was examined.
      MEASUREMENTS: CD4-positive T-lymphocyte counts and serum p24 antigen levels were
      determined. Plasma area under the ddl concentration-time curve was determined for
      a single dose and at steady state. RESULTS: Increases in CD4-positive T
      lymphocyte counts were independent of ddl exposure and were proportional to the
      starting CD4 count. Suppression of circulating p24 antigen was influenced by
      cumulative exposure to ddl and was statistically significant. CONCLUSIONS: The
      CD4-positive T-lymphocyte count increased at low ddl concentrations or exposures;
      the extent of this increase was directly proportional to the patient's CD4 count
      at the start of therapy. Suppression of p24 antigen was related to cumulative
      exposure to ddl. Therapeutic responses can probably be obtained with ddl, while
      minimizing long-term toxicity, using daily doses of 10 mg/kg body weight, or
      less.

PMID- 1347443
TI  - Surrogate markers in AIDS: where are we? Where are we going?

PMID- 1347444
TI  - Polyarteritis nodosa and hepatitis C virus infection.

PMID- 1347445
TI  - Fifth International Conference on Antiviral Research. Vancouver, B.C., Canada, 8
      13 March 1992. Abstracts.

PMID- 1347446
TI  - Asthma: a follow up statement from an international paediatric asthma consensus
      group.

PMID- 1347447
TI  - The angiotensin AT2 receptor stimulates protein tyrosine phosphatase activity and
      mediates inhibition of particulate guanylate cyclase.
AB  - The signalling mechanism and cellular targets of the AT2 receptor are still
      unknown. We report that angiotensin II (Ang II) inhibits basal and atrial
      natriuretic peptide stimulated particulate guanylate cyclase (pGC) activity
      through AT2 receptors in rat adrenal glomerulosa and PC12W cells. This inhibition
      is blocked by the phosphotyrosine phosphatase (PTPase) inhibitor orthovanadate
      but not by the Ser/Thr phosphatase inhibitor okadaic acid, suggesting the
      involvement of a PTPase in this process. Moreover, Ang II induces a rapid,
      transient and orthovanadate sensitive dephosphorylation of phosphotyrosine
      containing proteins in PC12W cells. Our findings suggest that AT2 receptors
      signal through stimulation of a PTPase and that this mechanism is implicated in
      the regulation of pGC activity. This observation is also the first example of
      hormonal inhibition of basal pGC activity.

PMID- 1347448
TI  - Studies on cytosolic guanylate cyclase from human placenta.
AB  - We have purified the soluble form of guanylate cyclase from human placenta
      greater than 2400-fold. The enzyme shared several characteristics with the enzyme
      purified from other sources including molecular mass and subunit composition,
      activation by divalent cations, inhibition by ATP and Michaelis constants. The
      enzyme, however, had a lower absorption maximum in the Soret region (417 +/- 1
      nm) than the enzyme from other sources and was activated only one-fifth as much
      by nitric oxide as the bovine lung enzyme. It appears that the heme prosthetic
      group in the human placental enzyme may be hexa-coordinate and in the bovine lung
      enzyme the heme group may be penta-coordinate.

PMID- 1347449
TI  - [Life saving glance diagnosis in type IIb multiple endocrine neoplasia].
AB  - Medullary carcinoma of the thyroid gland is a feature of multiple endocrine
      neoplasia, type IIb (MEN IIb). The cancer frequently gives rise to metastases in
      early life. Marfanoid habitus and virtually pathognomic mucosal ganglioneuromas,
      often situated on the tongue, enable early diagnosis. These stigmata should alert
      the clinician to the possibility of MEN IIb before medullary carcinoma is
      clinically manifest. We now believe that it is reasonable to perform a total
      thyroidectomy in children with the typical physical appearance of this syndrome
      regardless of age since medullary carcinoma of the thyroid gland appears in
      almost every case. Calcitonin, a hormone secreted by the C-cells, serves as a
      plasma tumor marker. Intravenously administered, pentagastrin is a potent
      secretagogue which is very useful in the early diagnosis of either primary or
      recurrent medullary carcinoma. With this pentagastrin test, a laboratory
      screening program is possible allowing the clinician, specialist, to recognize
      the syndrome.

PMID- 1347450
TI  - The same gamma-glutamyl transpeptidase RNA species is expressed in fetal liver,
      hepatic carcinomas, and rasT24-transformed rat liver epithelial cells.
AB  - In rats, gamma-glutamyl transpeptidase (gamma GT) exists as a single-copy gene,
      and three distinct species of RNA (types I, II, and III) that differ in their 5'
      untranslated regions have been identified. To compare steady-state levels of
      these gamma GT RNAs in rat tissues, hepatic carcinomas, and cultured cells, we
      used RNA dot-blot hybridization and a reverse transcriptase-polymerase chain
      reaction (RT-PCR) technique with oligonucleotides specifically designed for each
      type of RNA. Fetal liver, hepatic carcinomas, rasT24-transformed rat liver
      epithelial (RLE) cells and pancreas make only type III RNA. Liver and
      untransformed RLE cells do not make detectable levels of gamma GT RNA. We found
      that both fetal and adult kidneys synthesize all three types of RNA, indicating
      that increases in gamma GT RNA known to occur after birth do not result from
      recruitment of additional RNA species. When we increased the sensitivity of the
      assay approximately 1000 fold by sequencing the RT-PCR product directly after an
      additional round of amplification, we found that very low levels of types I and
      II RNA were present in fetal liver, rasT24-transformed RLE cells, and pancreas,
      and that adult liver and untransformed RLE cells synthesized very low levels of
      all three RNA species. Rat-1 fibroblasts did not make levels of gamma GT RNA
      detectable by this method. These results demonstrate that different gamma GT RNA
      species are regulated differently during development and neoplastic
      transformation and that there is a commitment in some cell types to very-low
      level expression of gamma GT RNAs.

PMID- 1347451
TI  - Ozone-treated blood in the treatment of HIV infection.

PMID- 1347452
TI  - Non-adrenergic, non-cholinergic inhibitory responses to nerve stimulation in rat
      colonic circular muscle.
AB  - The nerve-mediated response to electrical field stimulation (EFS) in rat colonic
      circular muscle was investigated using the single sucrose-gap technique. EFS with
      a single pulse (0.4 ms, supramaximal voltage) elicited transient TTX-sensitive
      hyperpolarization (IJP) often followed by an 'off' depolarization associated with
      muscular contraction. No relaxation associated with the IJP could be seen unless
      tone was pharmacologically induced by carbachol (10(-6) M). IJPs were due to non
      adrenergic, non-cholinergic (NANC) nerve activation since they were not affected
      by atropine (10(-7) M) or guanethidine (10(-6) M) superfusion. The mechanism
      underlying the IJP was presumably an increase in K+ conductance, and the NANC
      neurotransmitter might open largely apamin-sensitive, Ca(2+)-dependent K+
      channels. Purines or vasoactive intestinal polypeptide (VIP) did not mimic the
      effects of NANC nerve stimulation. Therefore, the NANC inhibitory system,
      producing IJPs, in rat colonic circular muscle is not purinergic or VIPergic in
      nature.

PMID- 1347453
TI  - Somatostatin and growth hormone regulation in cancer.
AB  - Somatostatin analogues are used clinically in a variety of pituitary and
      gastroenteropancreatic tumours. In addition, they may influence breast and
      prostate growth either directly through somatostatin receptors or indirectly
      through inhibition of growth hormone and prolactin release. Somatostatin
      analogues may interfere with EGF/TGF alpha-stimulated growth of these tumours and
      can suppress circulating levels of IGF-I in addition.

PMID- 1347454
TI  - Classification of vasculitis.
AB  - Usually classifications of vasculitic syndromes are based on clinical and
      histopathologic findings because pathogenetic mechanisms are poorly understood. A
      subcommittee of the Diagnostic and Therapeutic Criteria Committee of the American
      College of Rheumatology recently developed classification criteria for seven
      major vasculitic disorders through the analysis of prospectively collected
      patient data from 48 centers. Using two classification methods, the subcommittee
      derived criteria for polyareritis nodosa, Churg-Strauss syndrome, Wegner's
      granulomatosis, hypersensitivity vasculitis, Henoch-Schonlein purpura, giant cell
      (temporal) arteritis, and Takayasu's arteritis. Although such criteria may
      identify typical patients with a distinct form of vasculitis, they are not
      intended to establish a diagnosis in an individual patient; rather, they should
      aid comparability of different patient groups in various research endeavors.

PMID- 1347455
TI  - Therapeutic potential of terbinafine (Lamisil) in dermatomycoses. Proceedings of
      symposium, 2nd Congress of the European Academy of Dermatology and Venereology,
      Athens, Greece, 10 October 1991.

PMID- 1347456
TI  - Transport of L-glutamic acid in the fission yeast Schizosaccharomyces pombe.
AB  - Transport of L-glutamic acid into the fission yeast Schizosaccharomyces pombe
      grown to the early stationary phase and preincubated for 60 min with 1% D-glucose
      is practically unidirectional and is mediated by a single uphill transport system
      with a KT of 170 microM and Jmax of 4.8 nmol min-1 (mg dry wt.)-1. The system
      proved to be rather non-specific since all the amino acids transported into the
      cells acted as potent competitive inhibitors. It has a pH optimum at 3.0-4.0, the
      accumulation ratio of L-glutamic acid is highest at a suspension density of 0.6
      1.0 mg dry wt. per ml and decreases with increasing L-glutamic acid
      concentrations in the external medium. The system present in the cells after
      preincubation with D-glucose is unstable and its activity decays after washing
      the cells with water or after stopping the cytosolic proteinsynthesis with
      cycloheximide, with a half-time of 24 min in a reaction significantly retarded by
      phenylmethylsulfonyl fluoride, a serine proteinase inhibitor. The synthesis of
      the transport protein appears to be repressible by ammonium ions.

PMID- 1347457
TI  - Origins and fates of fatty acyl-CoA esters.

PMID- 1347458
TI  - Dietary alpha-linolenic acid deficiency in adult rats for 7 months does not alter
      brain docosahexaenoic acid content, in contrast to liver, heart and testes.
AB  - In adult rats, 22:6(n - 3) dietary deficiency does not affect brain membranes,
      but has a significant effect on some other visceral organs. 60-day-old male rats
      fed a diet containing sufficient amounts of both linoleic and alpha-linolenic
      acid were divided into three groups. One group continued the same diet; the
      second was fed a diet containing 2% sunflower oil, the third was fed 10%
      sunflower oil (sunflower oil contains linoleic acid, but trace amount of alpha
      linolenic acid). Animals were killed different times after receiving the new
      diets (1 to 31 weeks). For animals fed the diets containing only sunflower oil,
      deficiency in cervonic acid content (DHA, docosahexaenoic acid, 22:6(n - 3)) was
      not detected in whole brain, myelin or nerve endings within 31 weeks. In
      contrast, this acid progressively declined in liver, heart and testes up to 3
      weeks and remained nearly stable thereafter. In parallel to the reduction of
      cervonic acid content, 22:5(n - 6) content increased in liver and heart, but not
      in testes. It also increased in brain, nerve endings and myelin from week 3, 6
      and, 9 respectively. These results suggest that brain cervonic acid is highly
      preserved or is maintained at the expense of other organs.

PMID- 1347459
TI  - Role of adrenergic and cholinergic mediators in salivary phospholipids secretion.
AB  - The influence of adrenergic and cholinergic mediators on phospholipid secretion
      in rat sublingual salivary gland cells maintained in the presence of [3H]choline
      was investigated. The secretion of [3H]choline-containing phospholipids over 30
      min period averaged 1.93% of the total cellular labeled phospholipids in the
      absence of any mediator, and was enhanced by beta-adrenergic agonist,
      isoproterenol, to a greater extent than the cholinergic agonists, pilocarpine and
      carbachol. A 2.9-fold increase in phospholipid secretion occurred with
      isoproterenol, while pilocarpine and carbachol evoked only 1.3-fold increase. The
      effect of isoproterenol was inhibited by alprenolol and that of pilocarpine and
      carbachol by atropine. In contrast to pilocarpine and carbachol, the enhanced
      phospholipid secretion due to isoproterenol was accompanied by an increase in
      cAMP concentration. The secretion of phospholipids was also stimulated by
      dibutyryl-cAMP and the protein kinase C activator, phorbol myristate acetate, but
      not by 4 alpha-phorbol 12,13-didecanoate which does not activate protein kinase
      C. Furthermore, the effects of dibutyryl-cAMP and phorbol myristate acetate were
      additive. The phospholipids secreted in response to isoproterenol exhibited a 52%
      decrease in lysophosphatidylcholine, while those secreted in response to
      pilocarpine and carbachol showed a 21-23% lower content of phosphatidylcholine,
      and were enriched in lysophosphatidylcholine (2.6-2.8-fold) and sphingomyelin
      (1.5-1.6-fold). The results indicate that salivary phospholipid secretion remains
      mainly under beta-adrenergic regulation, while the phospholipid makeup of the
      secretion is under cholinergic control.

PMID- 1347460
TI  - Identification of pristanoyl-CoA oxidase as a distinct, clofibrate non-inducible
      enzyme in rat liver peroxisomes.
AB  - In this paper we describe the identification of pristanoyl-CoA oxidase activity
      in rat liver peroxisomes. This activity was not stimulated by clofibrate feeding.
      Furthermore, the activity was found in multiple tissues. These results show that
      pristanoyl-CoA oxidase is different from any of the known oxidases which include
      a clofibrate-inducible acyl-CoA oxidase and the recently identified cholestanoyl
      CoA oxidase. Gelfiltration and chromatofocusing experiments provide conclusive
      evidence that we are dealing with a novel acyl-CoA oxidase with a unique function
      in peroxisomal beta-oxidation.

PMID- 1347461
TI  - Cloning and nucleotide sequence of the Brucella abortus groE operon.
AB  - The cloning and sequencing of the Brucella abortus groES and groEL genes are
      reported. The genes are adjacent on the Brucella chromosome, and presumably
      comprise a functional operon. Putative promoter and terminator sequences are also
      identified. The groES gene exhibits 60%, and the groEl gene 69%, sequence
      identity with the corresponding Escherichia coli genes.

PMID- 1347463
TI  - Abnormalities of liver function during HIV seroconversion illness.

PMID- 1347462
TI  - Cloning of HSP60 (GroEL) operon from Clostridium perfringens using a polymerase
      chain reaction based approach.
AB  - Using degenerate oligonucleotide primers for conserved regions of HSP60, a 0.6
      kilobase fragment of Clostridium perfringens DNA was amplified by the polymerase
      chain reaction. The amplified fragment was used as a probe to isolate a genomic
      clone containing the C. perfringens HSP60 operon. The clone contained two open
      reading frames homologous to the GroES and GroEL (or HSP60) family of bacterial
      and eukaryotic proteins as well as other upstream and downstream sequences. The
      approach described here, employing this set of degenerate oligonucleotide
      primers, could be used to clone HSP60 gene/cDNA from any species.

PMID- 1347464
TI  - Cranial polyneuropathy and brainstem disorder at the time of seroconversion in
      HIV infection.

PMID- 1347465
TI  - Pathogenesis of peritoneal fibrosing syndromes (sclerosing peritonitis) in
      peritoneal dialysis.
AB  - Drawing from diverse sources including epidemiological and clinical data,
      surgical observations, histopathology, serosal healing responses to fibrin and
      fibrinolysis, tissue reaction to chronic exposure, and to exo- and endotoxins,
      new information on mesothelial stem cells, autocrine and paracrine influences on
      their proliferation and collagen synthesis, and the effect of glucose on
      fibroconnective tissue, we have begun to piece together the pathogenetic jigsaw
      of fibrosis in continuous ambulatory peritoneal dialysis (CAPD). The reaction of
      peritoneal mesothelium and stroma to the stress of continual dialysis results in
      a spectrum of alterations ranging from opacification through a tanned peritoneum
      syndrome to sclerosing encapsulating peritonitis (SEP). Any agent that causes
      irritation of the mesothelial layer and induces serositis, or single severe or
      multiple episodes of peritonitis resulting in mesothelial loss, predisposes the
      peritoneum to fibroneogenesis. An accurate definition of the histopathological
      changes of peritoneal thickening is a prerequisite for defining pathogenesis.
      This paper is the first attempt to create such a framework. It is evident from
      many areas of study that fibrin deposition and fibrinolysis, hyalinization of the
      superficial stromal collagen possibly tanned through nonenzymatic glycosylation
      by dialysate glucose and the proliferative potential of mesothelial stem cells
      play an important and possibly interdependent role in excessive fibroneogenesis
      in certain patients on CAPD. Many of the pieces of the jigsaw are obviously still
      missing, and the picture is most surely incomplete. Nevertheless, the outline of
      the pathologic and etiologic landscape should now be discernible.

PMID- 1347466
TI  - Inhibition of pyruvate dehydrogenase complex by antipsychotic drugs.

PMID- 1347467
TI  - Review article: maintenance treatment with H2-receptor antagonists for peptic
      ulcer disease.
AB  - In recent years a number of different strategies for managing patients with
      peptic ulcer disease have become available. The present review discusses the
      relative merits of each form of treatment. Intermittent treatment (whether given
      in response to symptoms or as a prophylactic regimen prescribed seasonally or at
      weekends) fails to prevent ulcer recurrence and leaves patients at risk of
      haemorrhage and perforation. Anti-Helicobacter pylori therapy, although useful in
      certain circumstances, cannot be recommended for all patients with ulcer disease
      because of side effects and, in any case, requires further assessment of
      efficacy. Gastric surgery reduces ulcer recurrence and complications, but
      operations which have a low incidence of side effects are associated with higher
      rates of ulcer recurrence, particularly when patients are followed up for more
      than 10 years. Long-term continuous maintenance treatment with H2-receptor
      antagonists for 5 or more years effectively prevents ulcer recurrence in the
      majority of patients and significantly reduces the risk of ulcer complications.
      In addition, maintenance treatment has proved to be safe and is well tolerated by
      patients. Maintenance treatment with H2-receptor antagonists is the preferred
      option for the management of patients with peptic ulcer disease.

PMID- 1347468
TI  - Clinical tolerance to three 5-aminosalicylic acid releasing preparations in
      patients with inflammatory bowel disease intolerant or allergic to
      sulphasalazine.
AB  - The clinical tolerance to three 5-aminosalicylic acid (5-ASA) releasing
      preparations (mesalazine, olsalazine and balsalazide) was assessed in a
      consecutive series of 43 patients with inflammatory bowel disease who were
      intolerant to sulphasalazine. The relative contributions to the side-effects of
      sulphasalazine made by its two components, 5-ASA and sulphapyridine, were also
      assessed in these patients. Thirty-nine (91%) patients were able to tolerate at
      least one of the three 5-ASA preparations. Only four (9%) patients were
      intolerant to all preparations, having adverse reactions previously experienced
      with sulphasalazine and presumably related to 5-ASA rather than sulphapyridine.
      The clinical tolerance to mesalazine (63%), olsalazine (70%) and balsalazide
      (70%) was similar, and tolerance to one drug only was found in nine (18%)
      patients. The commonest adverse reactions associated with 5-ASA preparations were
      gastrointestinal. Diarrhoea was a problem in five patients during treatment with
      olsalazine and three each while on mesalazine and balsalazide. Allergic reactions
      from 5-ASA preparations were uncommon; of ten patients with rash following
      sulphasalazine only one developed a rash with mesalazine. The results of this
      study indicate that the vast majority of patients with inflammatory bowel disease
      can be managed with at least one of these four 5-ASA containing preparations and
      that the side-effects of sulphasalazine are multifactorial in aetiology, some
      being due to the parent molecule, and some to one of its two metabolites, 5-ASA
      and sulphapyridine.

PMID- 1347469
TI  - The p locus is closely linked to the mouse homolog of a gene from the Prader
      Willi chromosomal region.

PMID- 1347470
TI  - The locus Om, responsible for the DDK syndrome, maps close to Sigje on mouse
      chromosome 11.
AB  - The DDK inbred strain of mouse has a striking particularity: when DDK females are
      crossed to males of other strains they exhibit a reduced fertility, whereas the
      reciprocal crosses (non-DDK females x DDK males) are fertile (Wakasugi et al.
      1967; Wakasugi 1973). The low fertility results from an early embryonic
      lethality, the F1 embryos dying near the late morula-early blastocyst stage.
      Genetic analyses (Wakasugi 1974) and nuclear and cytoplasmic transfers (Renard
      and Babinet 1986; Babinet et al. 1990; Mann 1986), have shown that the failure of
      the embroys to develop is due to an incompatibility between a DDK maternally
      encoded cytoplasmic product and the non-DDK paternal genome. In order to
      elucidate the genetic determinism of this embryonic lethality, we have analyzed
      the fertility of male progeny from a backcross BALB/c females x (BALB/c x DDK)F1
      males and that of males from a set of recombinant inbred (RI) strains,
      established from DDK and BALB/c progenitors, when mated with DDK females. Our
      results indicate that a single locus, Om, is responsible for the DDK syndrome and
      is located on Chromosome (Chr) 11, very close to the Sigje locus.

PMID- 1347471
TI  - Multiple sites of crossing over within the Eb recombinational hotspot in the
      mouse.
AB  - The Eb gene of the mouse major histocompatibility complex (MHC) contains a well
      documented hotspot of recombination. Twelve cases of intra-Eb recombination
      derived from the b, d, k and s alleles of the Eb gene were sequenced to more
      precisely position the sites of meiotic recombination. This analysis was based on
      positioning recombination breakpoints between nucleotide polymorphisms found in
      the sequences of parental haplotypes. All twelve cases of recombination mapped
      within the second intron of the Eb gene. Six of these recombinants, involving the
      k and s haplotypes, mapped to two adjoining DNA segments of 394 and 955 base
      pairs (bp) in the 3' half of the intron. In an additional two cases derived by
      crossing over between the d and s alleles, breakpoints were positioned to
      adjoining segments of 28 and 433 bp, also in the 3' half of the intron. Finally,
      four b versus k recombinants were mapped to non-contiguous segments of DNA
      covering 2.9 kb and 1005 bp of the intron. An analysis of the map positions of
      crossover breakpoints defined in this study suggests that the second intron of
      the Eb gene contains a recombinational hotspot of approximately 800-1000 bp which
      contains at least two closely linked recombinationally active sites or segments.
      Further examination of the sequence data also suggests that the postulated
      location for the recombinational hotspot corresponds almost precisely to an 812
      bp sequence that shows nucleotide sequence similarity to the MT family of middle
      repetitive DNA.

PMID- 1347472
TI  - Localization of growth arrest-specific genes on mouse chromosomes 1, 7, 8, 11,
      13, and 16.
AB  - Growth arrest in NIH3T3 cells is associated with increased expression of a
      variety of mRNAs, several of which have been isolated as cDNA clones. Six of
      these growth arrest-specific (Gas) genes were mapped by following the inheritance
      of DNA restriction fragment length variants (RFLVs) associated with them in
      panels of recombinant inbred (RI) strains of mice and in the progeny of
      backcrosses both between laboratory mouse strains and between a laboratory strain
      and Mus spretus. The six genes are unlinked. Gas-1 maps to Chromosome (Chr) 13,
      Gas-2 to Chr 7, Gas-3 to Chr 11, Gas-4 to Chr 16, Gas-6 to Chr 8, and Gas-10 to
      Chr 1.

PMID- 1347473
TI  - Mapping of six DNA markers on mouse chromosome 17.

PMID- 1347474
TI  - A strategy for rapid production and screening of yeast artificial chromosome
      libraries.
AB  - We describe methods for rapid production and screening of yeast artificial
      chromosome (YAC) libraries. Utilizing complete restriction digests of mouse
      genomic DNA for ligations in agarose, a 32,000-clone library was produced and
      screened in seven weeks. Screening was accomplished by subdividing primary
      transformation plates into pools of approximately 100 clones which were
      transferred into a master glycerol stock. These master stocks were used to
      inoculate liquid cultures to produce culture "pools," and ten pools of 100 clones
      were then combined to yield superpools of 1,000 clones. Both pool and superpool
      DNA was screened by polymerase chain reaction (PCR) and positive pools
      representing 100 clones were then plated on selective medium and screened by in
      situ hybridization. Screening by the two tiered PCR assay and by in situ
      hybridization was completed in 4-5 days. Utilizing this methodology we have
      isolated a 150 kb clone spanning the alpha 1(I) collagen (Col1a1) gene as well as
      40 kb clones from the Hox-2 locus. To characterize the representation of the YAC
      library, the size distribution of genomic Sal I fragments was compared to that of
      clones picked at random from the library. The results demonstrate significant
      biasing of the cloned fragment distribution, resulting in a loss of
      representation for larger fragments.

PMID- 1347475
TI  - Genomic organization and nucleotide sequence of a long mosaic repetitive DNA in
      the mouse genome.
AB  - A long mosaic repetitive sequence (LMRS) was isolated from a mouse liver genome
      library using a mouse repetitive DNA as a probe. LMRS exhibits the following
      features: (1) it is almost 15 kb in length; (2) it is partly organized in tandem
      array and frequently interrupted by other repeated sequences; and (3) it is
      located predominantly on the A3 band of the mouse X Chromosome (Chr). One
      fragment of LMRS (B6) shows restriction fragment length polymorphism (RFLP)
      between different mouse strains, and is thus potentially useful for mapping
      studies. The nucleotide sequence confirms a mosaic organization of LMRS which
      includes three repeats in the 5' part, showing similarity with the 5' end of L1Md
      A2, and seven long A + T rich segments in the central part of the element. Our
      findings suggest that this sequence may have arisen from the duplication of an
      ancestral motif and has expanded by successive waves of amplification and
      invasion by foreign sequences.

PMID- 1347477
TI  - Chromosomal localization of two cell surface-associated molecules of potential
      importance in development: midkine (Mdk) and basigin (Bsg).

PMID- 1347478
TI  - Factors affecting blood stem cell collections following high-dose
      cyclophosphamide mobilization in lymphoma, myeloma and solid tumors.
AB  - Sixty patients with malignancy were enrolled in a study of high-dose chemotherapy
      and peripheral blood stem cell transplantation (PBSCT). Stem cells were harvested
      prior to PBSCT using high-dose cyclophosphamide (CY) mobilization (4 or 7 g/m2)
      with collection of a median of 4.6 x 10(8)/kg mononuclear cells (range 0.2-9.5)
      and 21.6 x 10(4)/kg colony forming unit-granulocyte/macrophage (CFU-GM) (range
      0.1-220). Forty-seven patients were mobilized once, 11 required two cycles and
      two required three cycles. Eight patients (13%) failed to reach the optimum CFU
      GM target (greater than 15 x 10(4)/kg) following CY mobilization. A number of
      factors identified those patients who were likely to achieve optimum CFU-GM
      collections with CY mobilization. These included the use of the higher CY
      mobilization dose, a longer interval from last chemotherapy cycle to
      mobilization, and a higher premobilization bone marrow CFU-GM level. Patient's
      age, the degree of bone marrow infiltration, the nature of disease or the number
      of pre-mobilization chemotherapeutic cycles did not affect the ability to collect
      optimum CFU-GM numbers. Whilst the mobilization procedure was associated with
      moderate non-hematologic toxicity, significant hematological morbidity was
      observed primarily in patients mobilized using the 7 g/m2 dose. Refinements to
      the protocol, in particular the use of hematopoietic growth factors, are
      currently under investigation.

PMID- 1347479
TI  - Tardive dyskinesia. Patients' lack of awareness of movement disorder.
AB  - Of 113 patients in long-stay wards of a psychiatric hospital, 43 had TD. Twenty
      six of the 39 patients who consented to take part in the study were unaware of
      abnormal involuntary movements. These patients scored significantly lower on a
      short test of cognitive function than patients who were aware of such movements.
      The diagnosis of schizophrenia, particularly the 'defect' state with cognitive
      deficit and negative symptoms, was found to be associated with lack of awareness
      of TD.

PMID- 1347476
TI  - Mapping of the mouse ornithine decarboxylase-related sequence family.
AB  - A family of DNA sequences homologous to the mRNA encoding ornithine decarboxylase
      (ODC) and comprising approximately 12 members in the mouse genome has been
      analyzed genetically. The inheritance of variant DNA restriction fragments
      detected by ODC cDNA probes on Southern blots of DNA from inbred strain mice was
      determined in six sets of recombinant inbred (RI) mouse strains. The
      distributions of these variations among the RI strains were then compared with
      the RI strain distribution patterns (SDPs) of previously mapped loci. This
      allowed the identification of nine independent ODC-related loci, of which eight
      could be localized to specific regions of the mouse genome: Odc-rs1 near Lamb2 on
      Chromosome (Chr) 1; Odc-rs2 near Psp on Chr 2; Odc-rs5, a complex locus
      comprising at least 5-7 copies of the ODC sequence, associated with Igk on Chr 6;
      Odc-rs6 between Abpa and Tam-1 on proximal Chr 7; Odc-rs7 near Hbb on distal Chr
      7; Odc-rs12 near Agt and Emv-2 on distal Chr 8; Odc-rs8 associated with the Igh
      complex on Chr 12; and Odc-rs9 near Otf-3f on Chr 14. The ODC-related sequence
      family thus comprises a set of genomically dispersed "marker" loci, and alleles
      for several of these loci can be analyzed simultaneously in DNA from mice or cell
      lines. DNA from mice of 70 inbred strains has been characterized for alleles at
      all nine Odc-rs loci.

PMID- 1347480
TI  - Spouse-aided therapy with agoraphobics.
AB  - Sixty agoraphobics were treated by behavioural therapy (self-exposure in vivo)
      either with their partner involved in all aspects of treatment or without their
      partner. The two treatment formats were about equally effective. Behavioural
      treatment directed at the agoraphobia resulted in improvement irrespective of
      marital quality and partner involvement in the therapy. The effects of treatment
      led neither to a deterioration of the marriage nor to adjustment problems in the
      partner. Avoidance behaviour, intropunitivity and overprotection were found to
      predict treatment response. The partners of agoraphobics were not found to have
      psychological problems themselves.

PMID- 1347482
TI  - American Cancer Society Workshop on Guidelines and Screening for Breast Cancer.
      Pasadena, California, October 11-13, 1991.

PMID- 1347481
TI  - A prospective study of panic and anxiety in agoraphobia with panic disorder.
AB  - The features of panic and anxiety in the natural environment were studied by
      prospective self-monitoring in 39 patients with chronic agoraphobia and panic
      disorder. Panics overlapped greatly with anxiety episodes but were more intense.
      Panics occurred more often in public places than did anxiety episodes, but had
      otherwise similar symptom profile, time of occurrence, and antecedents. Most
      panics surged out of a pre-existing plateau of tonic anxiety which lasted most of
      the day. Spontaneous panics were less frequent than situational panics and
      occurred more often at home but were otherwise similar. These findings do not
      support the sharp distinction between panic and anxiety in DSM-III-R, not its
      emphasis on spontaneous panic in classifying anxiety disorders. Thoughts of dying
      and 'going crazy'/losing control accompanied only a minority of panic/anxiety
      episodes and seemed to be a product of intense panic rather than a cause.

PMID- 1347483
TI  - Cell proliferation in childhood acute leukemia. Comparison of Ki-67 and
      proliferating cell nuclear antigen immunocytochemical and DNA flow cytometric
      analysis.
AB  - The proliferative activity of bone marrow leukemia cells was determined by DNA
      flow cytometric (FCM) analysis and labeling index (LI) of Ki-67 monoclonal
      antibodies and proliferating cell nuclear antigen (PCNA) autoantibodies in 73
      children with acute leukemia. LI of Ki-67 varied greatly from patient to patient
      (range, 0.4% to 42.2%; mean, 18.8%) and differed significantly between acute
      lymphoblastic leukemia (ALL) and acute nonlymphoblastic leukemia (ANLL). In ALL,
      the Ki-67 LI showed a positive correlation with the S-phase fraction (SPF)
      determined by DNA FCM analysis, whereas, in ANLL, there was a discrepancy between
      the Ki-67 LI and SPF. In contrast, LI of PCNA varied less among the patients
      (range, 57.2% to 100%; mean, 90.3%), and the value was always higher than that of
      the Ki-67 LI in individual patients. A significant relationship between PCNA LI
      and the percentage of blast cells was found in peripheral blood leukocytes from
      patients with leukemia. These results suggest that the Ki-67 LI reflects
      differences in the proliferative activity depending on the subtype of the disease
      and that the PCNA LI is useful as a marker of proliferating cells.

PMID- 1347484
TI  - Internal mammary artery angiography should be a routine component of diagnostic
      coronary angiography.
AB  - Left internal mammary artery (LIMA) angiography was performed with diagnostic
      coronary angiography in 130 cases for which the coronary findings made use of the
      LIMA as a bypass graft a consideration. In 98% of the cases the approach to LIMA
      angiography was femoral with a 5F LIMA catheter first directed into the proximal
      subclavian and then advanced over a guidewire placed into the distal subclavian
      well beyond the origin of the LIMA. After withdrawing the wire the catheter was
      brought proximally to selectively cannulate and visualize the LIMA with nonionic
      contrast media. The only complication was a single transient occipital visual
      field loss. LIMA caliber too narrow to permit use as a graft was found twice,
      LIMA occlusion unrelated to prior surgery was found once, and LIMA occlusion
      related to prior surgery was found twice. Subclavian and/or vertebral stenosis
      was present five times. Large proximal branches of the LIMA best identified prior
      to surgery were present 12 times. Based on this experience, LIMA angiography 1)
      can be performed safely with a high degree of success, 2) demonstrates
      significant findings in 15% of cases, and 3) should therefore be performed
      whenever coronary angiographic findings make it appropriate to consider LIMA to
      coronary artery bypass grafting.

PMID- 1347485
TI  - Modulation of adhesion molecules on human large granular lymphocytes by
      interleukin-2 in vivo and in vitro.
AB  - The modulation of adhesion molecules on human large granular lymphocytes (LGL) by
      interleukin (IL)-2 was investigated both in vivo and in vitro. Intercellular
      adhesion molecule-1 (ICAM-1; CD54) expression increased on LGL of cancer patients
      receiving IL-2 adoptive immunotherapy. ICAM-1 expression on LGL isolated by
      Percoll gradient centrifugation, LGL purified, and expanded by adherence to
      plastic surfaces and LGL identified by Leu 19 (CD56) monoclonal antibody were
      increased significantly in response to IL-2 in vitro. Exposure of LGL to IL-1,
      interferon (IFN)-gamma, and tumor necrosis factor (TNF) in vitro did not induce
      ICAM-1. The expression of LFA-1 (CD11a/CD18), a receptor for ICAM-1, and other
      leukocyte adhesion molecules, including Mac-1 (CD11b/CD18) and p150,95
      (CD11c/CD18), was only maintained by IL-2. IL-2 induction of ICAM-1 and the
      maintenance of CD18 complex expression on small lymphocytes separated by Percoll
      gradients were similar to that on LGL. We conclude that IL-2 enhances the
      expression of ICAM-1 on multiple human lymphocyte populations including LGL
      effectors. Expression of the CD18 complex on LGL does not appear to be highly
      regulated by IL-2. These findings may have implications relevant to the role of
      these adhesion molecules in the activities of LGL modulated by IL-2.

PMID- 1347486
TI  - Mechanism of pokeweed mitogen inhibition of rhIL-4-induced human IgE synthesis.
AB  - Pokeweed mitogen (PWM) suppressed rhIL-4-induced IgE synthesis in a concentration
      dependent manner. When rhIL-4 was present from Day 0, PWM added to cultures on
      Day 0 or 3 inhibited MNC IgE synthesis but not when it was added on Day 6 or
      later. The concentration of interferon-gamma (IFN-gamma) in MNC culture
      supernatants varied directly with the quantity of PWM added. Conversely, rhIL-4
      stimulated MNC culture IgE concentrations varied inversely with the dose of PWM
      added and the IFN-gamma concentrations induced. The addition of a rabbit
      polyclonal neutralizing anti-human IFN-gamma antibody to rhIL-4 plus PWM
      stimulated cultures partially or completely reversed PWM-induced inhibition of
      rhIL-4-induced IgE synthesis. PWM failed to inhibit rhIL-4-induced IgE synthesis
      by isolated B cells cocultured with monocytes and T cells from a clone unable to
      produce IFN-gamma message or protein. These findings are consistent with the
      postulate that PWM inhibits rhIL-4-induced IgE synthesis by inducing the
      production of IFN-gamma.

PMID- 1347487
TI  - Suppression of collagen arthritis with antibodies to an arthritogenic,
      oligoclonal T cell line.
AB  - Rats immunized with type II collagen (CII) develop an immunologically mediated
      polyarthritis. T cells have been implicated in the pathogenesis of this model
      since they can adoptively transfer the disease. A CII-specific T cell line (VA),
      consisting of three distinct clones by Southern blot analysis, has been shown to
      be arthritogenic. Antibodies specific for this line were generated by immunizing
      rabbits. In an attempt to prevent collagen-induced arthritis (CIA), Louvain rats
      were injected with 1 ml of anti-VA ip on Days -1, +1, +3 and 0.5 ml on Day +5
      (early treatment). To evaluate its effect on existing disease, rats received anti
      VA on the day of arthritis onset and subsequently on 4 successive alternate days
      using the same dosage protocol (late treatment). Control rats received no
      therapeutic injections or were administered normal rabbit serum. All rats were
      immunized with CII on Day 0 to induce CIA. Rats administered antibodies using the
      early anti-VA treatment protocol had a significantly diminished incidence of
      arthritis compared to controls. Established arthritis was significantly
      diminished compared to controls in rats given the late anti-VA treatment. In both
      protocols, radiographic evidence of joint destruction was significantly reduced
      compared to controls. T cell phenotyping using flow cytometry analysis
      demonstrated that the anti-VA antibody therapy selectively eliminated a small
      subset of T cells since there was little difference in total T cell counts in the
      experimental versus control groups. Delayed type hypersensitivity and IgG
      antibody titers to CII were minimally decreased in the experimental versus
      control group. These results suggest that antibodies raised to an oligoclonal
      arthritogenic T cell line can suppress collagen arthritis. This may have
      implications with respect to 1) the size of the T cell receptor repertoire
      involved in the pathogenesis of collagen arthritis and 2) immunospecific
      protocols for CIA and other autoimmune diseases.

PMID- 1347488
TI  - Isolation and characterization of an IL-1-dependent IL-4-producing bovine CD4+ T
      cell clone.
AB  - An Ag-specific interleukin 1 (IL-1)-dependent bovine CD4+ Th cell clone, termed
      300B1, was isolated and found to resemble the previously described IL-1-dependent
      murine CD4+ Th2 cell clone, D10.G4.1. Both the 300B1 and the D10.G4.1 T cell
      clones proliferated to bovine (Bo) IL-1 beta, human (Hu) IL-1 alpha and IL-1
      beta, and murine IL-1 alpha when cells were costimulated with concanavalin A (Con
      A). Proliferation of the 300B1 clone, when costimulated with Con A, appeared to
      be IL-1-specific in that proliferation could not be promoted by BoIL-2, HuIL-3,
      HuIL-4, HuIL-5, or HuIL-6. The 300B1 clone produced interferon-gamma (IFN-gamma),
      but not IL-2 following stimulation with either Con A, Con A plus phorbol 12
      myristate 13-acetate or Ag plus antigen-presenting cells. Upon stimulation with
      Con A, the 300B1 clone expressed IL-4 mRNA and produced an autocrine growth
      factor (AGF) that could be inhibited by anti-HuIL-4 but not by anti-HuIL-2 Ab.
      The clonal derivation of the 300B1 clone was confirmed by isolating five 300B1
      subclones, all of which produced IFN-gamma and an AGF but not IL-2. Collectively,
      these results suggest the IL-1-dependent bovine 300B1 Th cell clone produces IL
      4, but not IL-2, as an AGF. Furthermore, the bovine Th cell clone appeared to
      share many characteristics of previously described murine Th2 cell clones except
      that the bovine clone produced IFN-gamma.

PMID- 1347490
TI  - No effect of a Taq1 polymorphism in DNA at the endothelin I (EDN1) locus on
      normal blood pressure level or variability.
AB  - Endothelin is a peptide reported to be one of the most potent vasoconstrictors
      known. Presumably, endothelin could play a role in the physiological regulation
      of blood pressure in healthy or hypertensive people. We have studied a normal
      restriction fragment length polymorphism (RFLP) at the endothelin-I (EDN1) locus
      detected with the restriction enzyme TaqI. In three different series comprising
      166, 120 and 207 unrelated individuals, we found no evidence for association
      between genotype in this polymorphism and level of systolic or diastolic blood
      pressure. In two series of 156 and 117 monozygotic (MZ) twin pairs, respectively,
      there was no difference between genotypes in within-pair variation in systolic or
      diastolic blood pressure. Thus neither "level gene" nor "variability gene"
      effects of normal genes at the EDN1 locus could be detected with the polymorphism
      analyzed, in healthy population samples.

PMID- 1347489
TI  - Onset of vecuronium neuromuscular block is more rapid in patients undergoing
      caesarean section.
AB  - This investigation was carried out in ten patients undergoing elective Caesarean
      section and the results were compared with those of a control group of ten
      nonpregnant females of the same age group. The study investigated the onset of
      vecuronium neuromuscular block and the conditions of tracheal intubation when
      ketamine (1.5 mg.kg-1)-vecuronium 100 micrograms.kg-1) sequence was used for
      rapid-sequence induction of anaesthesia. The ulnar nerve was stimulated supra
      maximally at the wrist with train-of-four stimuli every 20 sec, and the
      electromyographic response of the adductor pollicis muscle was displayed. The
      onset of 50% neuromuscular block as monitored by electromyography was shorter in
      the Caesarean group (80 +/- 30 sec) than in the control group (144 +/- 43 sec).
      The conditions of intubation at 50% block were adequate in both groups. Also, the
      onset of 90% block was shorter in the Caesarean group. The time of recovery to
      T1/control ratio of 25% was longer in the Caesarean group (46 +/- 10 min) than in
      the control patients (28 +/- 10 min). The results show that administration of
      vecuronium according to body weight results in a more rapid onset and delayed
      recovery of neuromuscular block in pregnant women undergoing Caesarean section
      than in the nonpregnant control patients.

PMID- 1347491
TI  - Combined total deficiency of C7 and C4B with systemic lupus erythematosus (SLE).
AB  - The first inherited combined total deficiency of C7 and C4B complement components
      associated with SLE is described in a young female. Functional C7 assays showed a
      homozygous C7 deficiency in the propositus and her sister, and an heterozygous
      one in their parents. C4 molecular analyses showed that both the propositus and
      her mother had two HLA haplotypes carrying only C4A-specific DNA sequences and a
      normal C4 gene number. Thus, only C4A proteins could be expressed, with resultant
      normal C4 serum levels. The coexistence of a combined complete C7 and C4B
      deficiency may therefore abrogate essential functions of the complement cascade
      presumably related to immune complex handling and solubilization despite an
      excess of circulating C4A. These findings challenge the putative
      pathophysiological roles of C4A and C4B and stress the need to perform both
      functional assays and C4 allotyping in patients with autoimmune pathology and low
      haemolytic activity without low serum levels of a classical pathway complement
      component.

PMID- 1347492
TI  - Evidence for the presence of activated CD4 T cells with naive phenotype in the
      peripheral blood of patients with rheumatoid arthritis.
AB  - We have investigated whether T cell activation in rheumatoid arthritis (RA)
      preferentially engages distinct T cell subpopulations in the peripheral blood
      (PB) and in the synovial fluid. We found that CD25 expression was enhanced among
      PB CD4 T cells of RA patients as compared with CD4 cells of patients with
      reactive arthritis, degenerative joint disease or of healthy controls. Within the
      CD4 T lymphocytes subset we found that the CD45RO- (naive) cells selectively in
      RA displayed higher levels of CD25 protein and of interferon-gamma mRNA
      expression when compared with the respective subset of all other investigated
      groups. These results show that in the PB of RA, but not in the PB of the other
      arthropathies or healthy controls, CD45RO-CD4 T lymphocytes exist which display
      well-defined signs of activation.

PMID- 1347495
TI  - New diagnostic techniques in gynecologic oncology.

PMID- 1347494
TI  - Suppression of efferent limb of testicular autoimmune response by a regulatory
      CD4+ T cell line in mice.
AB  - A murine T cell line (designated as C.Ts) as a mediator of suppression of
      experimental autoimmune orchitis (EAO) was established. The method of
      establishment of C.Ts cell line was preparing spleen cells from C3H/He mice
      hyperimmunized with testicular germ cells (TC) and the repeated selection of the
      lymphocytes in vitro by stimulation with mouse testicular antigens (mTA). The
      C.Ts cells were Thy1.2+, surface immunoglobulin-, CD3+, CD4+ and CD8-. The cells
      could suppress the induction of EAO when transferred into actively EAO-sensitized
      mice only at the pre-clinical stage of the disease (efferent limb of the
      autoimmune response). The transferred C.Ts cells significantly inhibited both
      cellular and humoral immune responses to TC in the recipients in an antigen
      specific manner. The disease suppression by C.Ts cells was found to depend upon
      their cell number, and their suppressive activity was markedly augmented by in
      vitro stimulation with mTA.

PMID- 1347496
TI  - IUGR-Macrosomia.

PMID- 1347493
TI  - Decreases in alpha beta T cell receptor negative T cells and CD8 cells, and an
      increase in CD4+ CD8+ cells in active Hashimoto's disease and subacute
      thyroiditis.
AB  - We examined peripheral lymphocyte subsets in patients with autoimmune thyroid
      disease, or subacute thyroiditis, in the active stage when possible. During
      destructive thyrotoxicosis arising from alpha beta T cell receptor (TCR) negative
      T (WT31-CD3+) cells and CD8 (CD4-CD8+) cells decreased and those of CD4+CD8+
      cells increased slightly, resulting in proportional increases in CD4 (CD4+CD8-)
      cells, non-T, non-B (CD5-CD19-) cells, and the CD4/CD8 cell ratio. Changes were
      similar in active subacute thyroiditis. During stimulative thyrotoxicosis in
      active Graves' disease, the numbers of such T lymphocyte subsets were not
      changed, but only the number of CD5+ B (CD5+CD19+) cells increased markedly,
      resulting in proportional decreases in total T (CD3+) cells, alpha beta+ TCR T
      (WT31+CD3+) cells, CD8 cells, and non-T, non-B cells. A serial study of some of
      the patients showed opposite changes in alpha beta TCR- T cells, the CD4/CD8 cell
      ratio, and CD5+ B cells between the active stages of Graves' and Hashimoto's
      diseases. alpha beta TCR- T cells were mostly gamma delta TCR+ T (IIF2+ CD3+)
      cells in these patients. These data suggest that alpha beta TCR-T (gamma delta
      TCR+ T), CD8, and CD4+ CD8+ cells are important in thyroid destruction in
      Hashimoto's disease and subacute thyroiditis, and that CD5+ B cells are important
      in thyroid stimulation in Graves' disease.

PMID- 1347497
TI  - The role of dopamine in mood disorders.
AB  - The findings on dopamine in mood disorders suggest that decreased dopamine
      activity is involved in depression, while increased dopamine function contributes
      to mania. This report reviews the considerable preclinical and clinical evidence
      supporting this hypothesis, with particular emphasis on specific subtypes of
      depression. We also discuss the importance of integrating these dopamine findings
      with dopamine brain circuitry and with other neurotransmitter theories of
      affective disorders.

PMID- 1347498
TI  - Increased tardive dyskinesia in alcohol-abusing schizophrenic patients.
AB  - Many schizophrenics have a diagnosis of substance abuse or dependence. We
      evaluated whether drug or alcohol abuse is an independent risk factor for tardive
      dyskinesia (TD) in schizophrenia. In a consecutive admission, clinical study of
      75 hospitalized schizophrenics, drug or alcohol abusers had significantly higher
      TD scores than nonabusers. The association of alcohol abuse or dependence with TD
      seemed independent from other risk factors for TD.

PMID- 1347499
TI  - Neuropsychological test scores and clinical response to neuroleptic drugs in
      schizophrenic patients.
AB  - Schizophrenic patients who showed greater neuropsychological deficits on the
      Luria-Nebraska Pathognomonic subscale (PATH) and Trail-Making Test showed less
      improvement during treatment with neuroleptic drugs than patients with lower
      scores on these neuropsychological tests. Other neuropsychological test scores we
      used were not consistently related to the patients' degree of clinical
      improvement during neuroleptic treatment. Only a few patients evidenced severe
      scores on either the PATH or TM tests, suggesting that more subtle
      neuropsychological deficits may identify a subgroup of schizophrenics who will
      show a relatively poor response to treatment with standard neuroleptic drugs.

PMID- 1347500
TI  - The human catechol-O-methyltransferase (COMT) gene maps to band q11.2 of
      chromosome 22 and shows a frequent RFLP with BglI.
AB  - We have been able to assign the human catechol-O-methyltransferase gene (COMT) to
      chromosome 22q11.2 by using Southern blot analysis of panels of somatic cell
      hybrids and chromosomal in situ hybridization. Furthermore, Southern blot
      analysis of DNA from blood and bone marrow samples of a patient with chronic
      myeloid leukemia (CML), having an extra Philadelphia chromosome (Ph1) in addition
      to the one produced by the reciprocal translocation between chromosomes 9 and 22,
      showed increased COMT and BCR gene dosage as compared to DNAs originating from
      CML patients with only one Ph1 chromosome or from chromosomally normal
      individuals. Control hybridizations of the same blot with TCRG- and TCRA-specific
      probes showed corresponding signal intensities in all samples. A relatively
      frequent two-allele COMT gene RFLP (PIC = 0.37) was recognized in DNAs digested
      with BglI. Our gene mapping result is in concordance with that previously
      reported by Brahe et al. (1986), who used an autoradiozymogram assay on different
      somatic cell hybrids to map this gene to chromosome 22.

PMID- 1347502
TI  - Permeability of bovine brain microvessel endothelial cells in vitro: barrier
      tightening by a factor released from astroglioma cells.
AB  - It has been shown both in vivo and in culture that astrocytes communicate with
      brain microvessel endothelial cells (BMECs) to induce many of the blood-brain
      barrier characteristics attributed to these unique cells. However, the results
      using cultured cells are conflicting as to whether this communication is
      dependent upon cell-cell contact. In this study we used primary cultures of
      bovine BMECs grown as monolayers on polycarbonate filters to study the formation
      of the barrier in vitro and examine its modulation by rat C6 glioma cells.
      Effects were examined by treating postconfluent BMEC monolayers with medium
      conditioned continually by C6 cells from the basolateral side to mimic the in
      vivo orientation. Cell monolayer integrity was assessed using electrical
      resistance and by measuring diffusion of uncharged molecules. BMEC monolayers
      form a functionally polarized and leaky barrier, with maximal resistance of 160
      omega . cm2 and significant flux of molecules of molecular weight less than 350
      Da. Treatment with rat or human astroglioma cells rather than pericytoma cells or
      transformed fibroblasts results in a concentration-dependent 200-440% increase in
      electrical resistance and a coincident 50% decrease in permeability to sucrose
      and dextran (70 kDa). The decrease in passive diffusion is most likely due to a
      change in tight junctions and not to transcellular vesicular traffic. The
      findings support that astroglioma cells release one or more signals that are
      required for cultured BMECs to express a "differentiated" phenotype associated
      with a tighter barrier, increased gamma-glutamyl transpeptidase activity, and
      decreased pinocytic activity. The relative ease and quickness of this culture
      system makes it amenable to studies on cell-cell interaction and regulation of
      barrier maintenance.

PMID- 1347501
TI  - [Acquired protein C deficiency in ulcerative colitis. The cause of thromboembolic
      complications].
AB  - Three patients with an acute exacerbation of ulcerative colitis (a 40-year-old
      and a 31-year-old man and a 30-year-old woman) developed a protein C deficiency
      (serum protein C activity between 32 and 48%). In the two men the protein C
      deficiency was diagnosed only after the onset of severe thromboembolic
      complications (cavernous sinus thrombosis; pulmonary embolism) during heparin
      treatment. But in the woman protein C activity was measured immediately after
      hospital admission (in the knowledge of the first two cases) even before heparin
      administration was started. All three patients received treatment with
      sulphasalazine (3 g daily) and fluocortolone (60 mg daily), as well as full
      heparinization (22,500-36,000 IU daily). Protein C activity returned to normal on
      remission of the ulcerative colitis (in one case only after subtotal colectomy).
      These case reports show that acquired protein C deficiency can be reversed by
      rigorous treatment of the underlying disease.

PMID- 1347503
TI  - Radioligand binding studies of the atypical beta 3-adrenergic receptor in rat
      brown adipose tissue using [3H]CGP 12177.
AB  - Two populations of [3H]CGP 12177 binding sites exist in rat interscapular brown
      adipose tissue (IBAT) plasma membranes. The majority of binding sites are of low
      affinity with a Kd of 31 nM, a value in close agreement with that for the Kd of
      [3H]CGP 12177 binding to a cloned rat beta 3-adrenergic receptor (AR) expressed
      in CHO cells (44 nM). Competition binding studies demonstrate that the Ki values
      of the cloned rat beta 3-AR and of the low affinity sites in IBAT are 45 and 29
      nM, respectively, for BRL 37344 and 1.4 and 1.0 microM, for (-)-propranolol.
      These findings strongly suggest that the low affinity [3H]CGP 12177 binding site
      measured in IBAT plasma membranes represents the atypical beta 3-AR in this
      tissue.

PMID- 1347504
TI  - Structure of holo-chaperonin studied with electron microscopy. Oligomeric cpn10
      on top of two layers of cpn60 rings with two stripes each.
AB  - A structural model of holo-chaperonin, known as a protein-folding control protein
      comprising 60 kDa (cpn60) and 10 kDa polypeptides (cpn10), is proposed based on
      the electron microscopic images of holo-chaperonin from Thermus thermophilus and
      cpn60 from Paracoccus denitrificans. Isolated Paracoccus cpn60 shows very similar
      images to those of Escherichia coli tetradecameric cpn60, a seven-membered ring
      in the top view and a rectangular shape with four stripes in the side view.
      However, a small number of half-thick rectangles with two stripes are also seen
      which indicates that a single cpn60-heptamer ring has two stripes parallel to the
      plane of the ring. Thermus holo-chaperonin shows a bullet-like shape in the side
      view, and antibody against cpn10 binds only to the round side of the bullet. We
      conclude that a single cpn60-heptamer ring with two stripes stacks into two
      layers, and a cpn10 oligomer binds to one side of the layers.

PMID- 1347505
TI  - Subcellular localisation and processing of non-specific lipid transfer protein
      are not aberrant in Rhizomelic Chondrodysplasia Punctata fibroblasts.
AB  - The import into peroxisomes and maturation of peroxisomal 3-oxoacyl-CoA thiolase
      are impaired in patients with the Rhizomelic form of Chondrodysplasia Punctata
      (RCDP). Here we show by means of immunoblotting and subcellular fractionation
      that non-specific lipid transfer protein (nsLTP), another peroxisomal protein
      synthesised as a larger precursor, is localised in peroxisomes and is present as
      the mature protein in RCDP fibroblasts. Thus the component of the import
      machinery defective in RCDP is not required for the import of nsLTP into
      peroxisomes.

PMID- 1347506
TI  - Neuroactive steroids.
AB  - Neuroactive steroids are natural or synthetic steroids that rapidly alter the
      excitability of neurons by binding to membrane-bound receptors such as those for
      inhibitory and (or) excitatory neurotransmitters. The best-studied neuroactive
      steroids are a series of sedative-hypnotic 3 alpha-hydroxy ring A-reduced
      pregnane steroids that include the major metabolites of progesterone and
      deoxycorticosterone, 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone)
      and 3 alpha,21-dihydroxy-5 alpha-pregnan-20-one (allotetrahydroDOC),
      respectively. These 3 alpha-hydroxysteroids do not interact with classical
      intracellular steroid receptors but bind stereoselectively and with high affinity
      to receptors for the major inhibitory neurotransmitter in brain, gamma-amino
      butyric acid (GABA). Biochemical and electrophysiological studies have shown that
      these steroids markedly augment GABA-activated chloride ion currents in a manner
      similar (but not identical) to that of anesthetic barbiturates. Several steroids
      have also been observed to have convulsant or proconvulsant properties, including
      the synthetic amidine 3 alpha-hydroxy-16-imino-5 beta-17-azaandrostan-11-one
      (RU5135) and the natural sulfate esters of pregnenolone and
      dehydroepiandrosterone. Several of these have been shown to be bicuculline or
      picrotoxin-like GABAA receptor antagonists. Examples of steroids that alter
      neuronal excitability rapidly by augmenting or inhibiting excitatory amino acid
      receptor-mediated responses have also been reported. Recently, allopregnanolone
      and allotetrahydroDOC have also been measured in brain and plasma where their
      levels have been shown to fluctuate in response to stress and during the estrous
      and menstrual cycles of rats and humans, respectively. Although the major
      fraction of allopregnanolone in tissue, including brain, is of adrenal and/or
      ovarian origin, appreciable levels of allopregnanolone can still be measured in
      the brains of adrenalectomized and/or oophorectomized animals. Receptor-active
      neurosteroids may represent an important class of neuromodulators that can
      rapidly alter central nervous system excitability via novel nongenomic
      mechanisms.

PMID- 1347508
TI  - Propranolol for portal hypertensive gastropathy: another virtue of beta-blockade?

PMID- 1347507
TI  - Hemodynamic effects of terbutaline, a beta 2-adrenoceptor agonist, in conscious
      rats with secondary biliary cirrhosis.
AB  - The hemodynamic responses to terbutaline - a selective beta 2-adrenoceptor
      agonist - were studied in conscious normal rats and in conscious rats with
      secondary biliary cirrhosis. Compared with those of normal rats, dose-response
      curves in cirrhotic rats indicated significantly decreased reactivity in arterial
      pressure and heart rate. Half-maximal effective dose was not significantly
      different between the two groups. Terbutaline induced significant, dose-dependent
      decreases in portal pressure in both normal rats (9.3%) and cirrhotic rats
      (13.8%). In normal rats, terbutaline administration (32 micrograms.min-1.kg-1
      body wt) increased both cardiac output and portal tributary blood flow, thus
      mimicking hemodynamic changes in cirrhotic rats. In cirrhotic rats, despite a
      significant increase in portal tributary blood flow (from 19.9 +/- 1.7 ml/min to
      22.7 +/- 1.5 ml/min), terbutaline decreased portal pressure from 17.4 +/- 1.0 mm
      Hg to 15.0 +/- 0.8 mm Hg. This study indicates that increased beta 2-adrenoceptor
      stimulation in cirrhotic rats may be involved in hyperdynamic circulation. The
      association of a decreased portal pressure and increased splanchnic blood flow
      suggests that beta 2-adrenoceptor stimulation may modulate hepatic and portal
      collateral vascular resistance.

PMID- 1347509
TI  - Controlling prescription of benzodiazepines.

PMID- 1347510
TI  - Drugs vs. other therapies.

PMID- 1347511
TI  - Induction of colitis in rats by 2-2'-azobis(2-amidinopropane) dihydrochloride.
AB  - Reactive oxygen metabolites (ROM) may play a role in the pathophysiology of
      inflammatory bowel disease (IBD) and ischemia-reperfusion-induced intestinal
      injury. Although there are many reports of intestinal mucosal injury associated
      with neutrophil-derived ROM, free radicals themselves have not been reported to
      induce intestinal mucosal injury. We administered intrarectally 2,2'-azobis(2
      amidinopropane) dihydrochloride (AAPH) to rats, an azo compound that generates
      free radicals in vitro. Acute mucosal injury was assessed histologically by light
      microscopy and biochemically by myeloperoxidase (MPO) activity. Intrarectal
      administration of AAPH (60, 90, 150 mg/kg) caused erythema, edema, and
      histologically verifiable mucosal inflammation. MPO activity was increased 9- to
      18-fold above the control level. The levels of thiobarbituric acid (TBA)
      reactants and sulfhydryls (SH) were significantly (P less than 0.01) increased
      and decreased, respectively, by 90 mg/kg AAPH. Sulfasalazine, 5-aminosalicylic
      acid, the LTB4 receptor antagonist SC-41930, and the antioxidant glutathione
      prevented the inflammation. This model of mucosal inflammation may be useful in
      evaluating new therapeutic agents for the treatment of IBD.

PMID- 1347512
TI  - Pattern of Sertoli cell degeneration in cryptorchid prepubertal testes.
AB  - Seventy-three testicular biopsies from 54 children (aged 2 months-14 years) with
      undescended testes were examined by light and electron microscopy. The biopsies
      included abdominal, inguinally fixed, inguinally moveable, and retractile testes.
      Alterations in Sertoli cell morphology were found in all biopsies. The
      alterations included dilated elements of rough endoplasmic reticulum,
      vacuolization of the cytoplasm, mitochondria with poorly preserved cristae,
      increase in electron density of the matrix, elongation of the nuclei, and
      irregularities of the nuclear membrane. According to the numerical appearance of
      these cells and to the extent of lesions in single Sertoli cells, seven phases in
      the continuous process of tubular alteration were distinguished. The most severe
      tubular damaged (phase VII) occurred when the seminiferous epithelium consisted
      exclusively of necrotic cells. All phases of tubular alterations were seen
      regularly in each of the biopsies investigated. Germ cells occurred only in
      phases I-IV and were never observed in tubules in phases V-VII. Significant
      differences became evident between inguinal and retractile testes by morphometric
      evaluation. It was demonstrated that the number of germ cells per cross-sectioned
      tubule (S/T value) correlated negatively with the percentage of tubules in phases
      V-VII. In contrast to inguinal testes, a complete absence of Sertoli cells and an
      S/T value less than 0.1 were never found in retractile testes and the percentage
      of tubules in phases V-VII was reduced significantly compared with inguinal
      testes. Our findings indicate that (i) maldescended testis in patients between 1
      and 15 years-of-age is associated with a special pattern of Sertoli cell
      degeneration; (ii) Sertoli cell degeneration is a continuous process, which can
      lead eventually to complete dissolution of the seminiferous epithelium; (iii)
      total degeneration is not related to age but is dependent on testicular position;
      (iv) a defined phase of degeneration excludes germ cell development, and
      therefore enhanced Sertoli cell degeneration in cryptorchid testes must also
      account for the reduction in germ cell number.

PMID- 1347513
TI  - Over-expression of p53 nuclear oncoprotein in colorectal adenomas.
AB  - p53 is a nuclear phosphoprotein which controls normal cell growth. Normal p53
      protein is undetectable by standard immunohistochemical staining and the over
      expression found in neoplastic cells correlates with the presence of point
      mutations of evolutionary conserved regions of the p53 gene. We examined the
      expression of p53 protein in a series of 36 colorectal adenomas (13 tubular, 17
      tubulovillous, 6 villous) showing different degrees of dysplasia (11 mild, 19
      moderate, 6 severe), 11 moderately differentiated adenocarcinomas (6 Duke's A, 4
      Duke's B, 1 Duke's C) and 5 metaplastic polyps using the polyclonal antibody CM1
      which recognises p53 protein in conventionally fixed and processed histological
      material. We found that 15 out of 36 colorectal adenomas showed p53
      immunoreactivity, although in 4 positive cases (26%) the staining was very focal
      (less than 0.1% positive cells). More than 80% of severely dysplastic adenomas
      showed strong p53 immunoreactivity and this over-expression was correlated with
      increased cell proliferative rate as detected by the proliferating-cell-nuclear
      antigen (PCNA) staining. p53 nuclear staining was also seen in 8 out of 11 (65%)
      colorectal adenocarcinomas as previously shown. Our data suggest that the p53
      gene mutation, with the subsequent over-expression of the protein, occurs in
      colorectal adenomas and may therefore be a fundamental genetic event underlying
      the dysplasia and loss of proliferative control that are characteristic of
      adenomas with malignant potential.

PMID- 1347514
TI  - Protein kinase C activity and expression in normal and adenomatous human
      pituitaries.
AB  - Protein kinase C (PKC) activity and expression were measured in 54 adenomas
      (prolactin (PRL)-, growth hormone (GH)- and non-secreting), 1 of them obtained
      from a patient treated with the dopamine agonist bromocriptine and 2 from
      patients treated with the somatostatin analog octreotide. They were also measured
      in normal human and rat pituitaries. Total PKC activity was measured by
      incorporation of 32P into histones, and PKC expression by dot blot
      immunoquantification using purified PKC as a standard. Both enzyme activity and
      expression were higher in adenomatous pituitaries than in normal human or rat
      pituitaries. PKC expression in GH-secreting and non-secreting tumors was
      significantly higher than that in PRL-secreting tumors. Furthermore, it was
      significantly higher invasive tumors than in non-invasive tumors. In the 3
      adenomas which were obtained from patients treated with bromocriptine or
      octreotide and which were used for PKC-activity measurement, particulate- and
      soluble-PKC activities were significantly lower than those measured in non
      treated adenomas.

PMID- 1347515
TI  - Basic fibroblast growth factor induces proliferation of a rat pancreatic cancer
      cell line. Inhibition by somatostatin.
AB  - AR4-2J, a rat pancreatic acinar-tumor cell line, was used to investigate long
      term effects of basic fibroblast growth factor (bFGF) and somatostatin on
      pancreatic cancer cells. We observed that bFGF stimulated cell proliferation when
      cells were cultured in serum-free medium. The effect was dose-dependent with half
      maximal and maximal effects at 25 pM and I nM bFGF, respectively. The
      somatostatin analog SMS 201-995 (SMS) decreased the growth-promoting effect of
      bFGF. The maximal effect was observed at I nM SMS and the half-maximal effect at
      20 pM SMS. Characterization of bFGF receptor-binding properties with [125I]bFGF
      revealed that AR4-2J cells exhibited 2 classes of bFGF binding site with
      respective KD values of 47 pM and 3 nM and binding capacities of 14 fmol and 0.9
      pmol/10(6) cells. High-affinity receptors correlated with bFGF stimulation of AR4
      2J cell growth, suggesting that the effects of bFGF are receptor-mediated.

PMID- 1347516
TI  - Human c-erbB-2 proto-oncogene product as a target for bispecific-antibody
      directed adoptive tumor immunotherapy.
AB  - To develop an efficient strategy for the targeting of anti-tumor effector cells,
      we prepared bispecific antibody (BsAb) containing anti-CD3 and an anti-c-erbB-2
      proto-oncogene product. The prepared BsAb specifically reacts with both c-erbB-2
      positive tumor cells and CD3+ CTL. Human CD4+ helper/killer T cells, induced from
      peripheral-blood mononuclear cells by activation with immobilized anti-CD3
      monoclonal antibody (MAb) plus IL-2, showed no significant cytotoxicity against
      tumor cells. However, treatment of human CD4+ helper/killer cells with the BsAb
      caused the induction of specific cytotoxicity against c-erbB-2-positive tumor
      cells. CD4+ helper/killer cells also produced significant amounts of IL-2 during
      co-culture with c-erbB-2-positive tumor cells in the presence of the BsAb.
      Moreover, by combination with the BsAb, CD4+ helper/killer cells showed a strong
      in vivo anti-tumor effect against c-erbB-2 transfectant or human colon-cancer
      cells implanted in nude mice. Our results strongly suggest that the c-erbB-2
      proto-oncogene product on human tumor cells may be a good target for BsAb
      directed adoptive tumor immunotherapy.

PMID- 1347517
TI  - An overview of the noncontraceptive benefits and risks of oral contraception.

PMID- 1347518
TI  - Norgestimate: a preclinical profile.

PMID- 1347519
TI  - The European experience: an overview.

PMID- 1347520
TI  - Clinical experience with a new norgestimate-containing oral contraceptive.
AB  - Research in the area of oral contraception currently focuses on the development
      of selective progestogens that combine targeted progestational and antiovulatory
      activity with a minimal potential for androgenicity. The present dual-center
      study was conducted to investigate the efficacy, tolerability, and safety of a
      new monophasic oral contraceptive (OC) containing 250 micrograms norgestimate in
      combination with 35 micrograms ethinyl estradiol (Ortho-Cyclen or Cilest). Ninety
      seven healthy women of childbearing age participated in the study: 37 received
      the new norgestimate/ethinyl estradiol combination OC as primary therapy and 31
      were switched over from other OCs. The norgestimate/ethinyl estradiol formulation
      was well tolerated and was associated with excellent cycle control. After six
      cycles of use, there were no statistically significant differences in the
      incidence of spotting or breakthrough bleeding compared with baseline, nor were
      there any significant changes in the incidence of headache, nausea, or mastalgia.
      Body weights remained constant for the duration of the study, as did systolic and
      diastolic blood pressures. Of particular note was the absence of any
      statistically significant alterations in metabolic parameters, including blood
      glucose or lipoprotein levels. These findings are consistent with the results of
      several other European studies and indicate that the norgestimate/ethinyl
      estradiol combination OC combines superior cycle control with minimal risk of
      androgenic side effects.

PMID- 1347521
TI  - Oral contraception: past, present, and future perspectives.
AB  - Oral contraceptives (OCs) were initially approved for unrestricted use in 1960 in
      the United States and have been used and studied extensively for 30 years. The
      initial formulations contained a fixed dose of estrogen and progestogen ingested
      for 21 days, with a seven-day pill-free interval. Subsequent formulations
      contained a sequential estrogen dose, a progestogen alone given daily, and
      variable doses of both progestogen and estrogen. Although the estrogen and
      progestogen doses employed in currently marketed OCs are markedly lower than
      those used in the OCs of the 1960s and 1970s, the excellent contraceptive
      efficacy of these compounds has not been compromised. The estrogen component
      produces a dose-related increase in serum globulin concentrations, triglycerides,
      and high-density lipoprotein (HDL) cholesterol, along with a decrease in low
      density lipoprotein (LDL) cholesterol, while the progestogen component causes
      peripheral insulin resistance, a decrease in HDL cholesterol, an increase in LDL
      cholesterol, and various androgenic effects. The effect of nicotine on
      thromboxane release acts synergistically with the elevated serum clotting factors
      to increase the incidence of both arterial and venous thrombotic events,
      particularly in women smokers over 35 years of age. However, there is no evidence
      of increased risk of myocardial infarction or stroke in healthy, nonsmoking women
      of any age who use OCs containing less than 50 micrograms estrogen. Likewise, the
      lower-dose estrogen/progestogen formulations do not have a clinically significant
      effect on glucose metabolism and have a neutral effect on lipoprotein metabolism.
      In addition, the many noncontraceptive health benefits associated with OCs are
      maintained with the lower-dose formulations. Thus, the low-dose formulations
      should improve the overall health of healthy, nonsmoking women as well as
      effectively prevent unwanted pregnancy.

PMID- 1347523
TI  - The Seventh International Conference on Chemical Modifiers of Cancer Treatment-
      Part 2. Clearwater, FL, February 2-5, 1991.

PMID- 1347522
TI  - Differential expression of human corneal and perilimbal ICAM-1 by inflammatory
      cytokines.
AB  - The mechanisms that regulate corneal infiltration by circulating leukocytes in
      inflammatory diseases are poorly understood. In this study, we investigated the
      effects of pro-inflammatory cytokines on corneal endothelial (CE) and stromal
      (CS) expression of intercellular adhesion molecule-1 (ICAM-1), a specialized cell
      surface glycoprotein that binds the leukocyte function antigen-1 (LFA-1) receptor
      present on all leukocytes and enhances immune responses. Using specific
      monoclonal antibody (mAb) to ICAM-1, immunohistochemical staining of intact human
      corneas resulted in discrete, granular reaction product in CE and CS cells as
      well as perilimbal vascular endothelium that increased dramatically when exposed
      to human recombinant interleukin-1-beta (rIL-1 beta), tumor necrosis factor-alpha
      (rTNF-alpha), and interferon-gamma (rIFN-gamma). Immunoreactive ICAM-1 in CE and
      CS cells was differentially increased by each of these cytokines. In contrast,
      immunoreactive endothelial-leukocyte adhesion molecule-1 and vascular cell
      adhesion molecule-1 were not detected in any CE or CS cells of unstimulated or
      cytokine-stimulated corneas. In standardized leukocyte adherence assays,
      neutrophil binding to CE surfaces of whole corneas increased significantly upon
      exposure to rIL-1 beta, rTNF-alpha, or rIFN-gamma (P less than 0.001). In
      parallel assays, mAb to ICAM-1 on CE cells or subunits of LFA-1 receptors on
      leukocytes, but not control mAb, significantly blocked leukocyte binding to
      unstimulated (P less than 0.01) or rIFN-gamma-stimulated corneas (P less than
      0.001). Our results indicate that: (1) ICAM-1 is expressed at low levels on
      unstimulated CE cells, CS cells, and perilimbal vascular endothelium; (2) ICAM-1
      may be augmented differentially in corneal and perilimbal tissue by pro
      inflammatory cytokines; and (3) ICAM-1 is a functional ligand mediating corneal
      leukocyte binding. Differential expression of ICAM-1 within corneal tissue may
      regulate keratitic precipitate formation, leukocyte trafficking and accumulation,
      and localized generation of immune responses.

PMID- 1347524
TI  - Insertion/deletion polymorphism and other restriction fragment length
      polymorphisms in the MCC gene.
AB  - The MCC gene is a candidate as a tumor suppressor gene for colorectal neoplasms.
      Further, MCC is tightly linked to the familial adenomatous polyposis (FAP) locus
      by linkage and physical analysis. Hence, restriction fragment length
      polymorphisms (RFLPs) of this gene might be very useful for presymptomatic
      diagnosis of individuals in families segregating mutant alleles of the APC gene.
      Here we report the identification of five polymorphic systems in MCC gene (both
      cDNA and genomic), one of which is an insertion/deletion polymorphism that is
      detectable by a polymerase chain reaction method. These five RFLP systems should
      be useful for linkage studies in FAP and for examining loss of heterozygosity at
      this locus in colonic polyps and tumors.

PMID- 1347526
TI  - Beta 2 agonist therapy: oral versus inhaled delivery.
AB  - Although there is a place for administering oral medication, the inhaled route of
      administration for both bronchodilator and prophylactic purposes has been
      definitely shown to be the preferred route in numerous studies. The rapid onset
      of action, equivalent activity, and reduction in systemic effects all should lead
      the clinician to this form of therapy. Care must be taken to ensure proper
      utilization of the different types of inhalational medication to optimize their
      effectiveness.

PMID- 1347525
TI  - Expression and characterization of kinase-active v-erbB protein using a
      baculovirus vector system.
AB  - The v-erbB gene is an oncogene of the avian erythroblastosis virus encoding a
      protein that is a truncated version of the epidermal growth factor receptor. The
      v-erbB protein was expressed alone or as polyhedrin-erbB fusion proteins using
      the Bombyx mori nuclear polyhedrosis virus vector. The expression level of the
      fusion protein whose polyhedrin portion consisted of only 8 amino-terminal amino
      acids was more than ten times higher than that of the non-fusion protein. Studies
      with tunicamycin showed that the recombinant v-erbB proteins were glycosylated.
      The recombinant protein autophosphorylated tyrosine residues, and phosphorylated
      a synthetic tyrosine-containing peptide and lipocortin I. These observations
      indicate that functional v-erbB protein can be expressed in silkworm-derived
      cells, and furthermore, that this system can be used for large-scale production.

PMID- 1347527
TI  - Isolation and characterization of a Xenopus cDNA which encodes a homeodomain
      highly homologous to Drosophila Distal-less.
AB  - A novel homeobox gene of Xenopus was isolated from the ovary cDNA library. The
      homeodomain of the encoded protein was homologous to that of Drosophila Distal
      less (Dll), and the gene was termed Xdll. The mRNA exists in a large amount in
      ovary, and in a small amount in testis, but was not detected in muscle, kidney,
      gut, and liver. The mRNA also occurs in a large amount in oocytes and is
      maintained in unfertilized eggs and cleavage stage embryos as a maternal mRNA at
      a low but distinctly detectable level. The amount of the mRNA per embryo
      increases gradually in later stages by zygotic expression. Embryo dissection
      experiment revealed that the transcript is abundant in the anterior region at the
      neurula stage, suggesting that Xdll may play a role in the establishment of the
      structures in the anterior part of the embryo.

PMID- 1347528
TI  - Characterization of two site-specifically mutated human dihydrolipoamide
      dehydrogenases (His-452----Gln and Glu-457----Gln).
AB  - Two site-specifically mutated human dihydrolipoamide dehydrogenases (His-452---
      Gln and Glu-457----Gln) were expressed in pyruvate dehydrogenase complex-deletion
      mutant Escherichia coli JRG1342. The expressed mutant E3s were purified to near
      homogeneity using DEAE-Sephacel and hydroxyapatite columns. The initial velocity
      measurements in the absence of products for the Gln-452 mutant E3 in the
      direction of NAD+ reduction showed parallel lines in double-reciprocal plots,
      indicating that the mutant E3, like wild-type enzyme, catalyzed E3 reaction via a
      ping-pong mechanism. The specific activity of the Gln-452 mutant E3 was about
      0.2% of that of wild-type enzyme. Its Km for dihydrolipoamide was dramatically
      increased by 63-fold. The substitution of His-452 to Gln resulted in a
      destabilization of the transition state of human E3 catalysis by about 6.4 kcal
      mol-1. The Gln-457 mutant E3, unlike wild-type enzyme, catalyzed E3 reaction via
      a sequential mechanism in the direction of NAD+ reduction based on the
      intersecting lines shown on double-reciprocal plots. Its specific activity
      decreased to 28% of that of wild-type enzyme. Its Km for dihydrolipoamide
      increased about 4.3-fold. The substitution of Glu-457 to Gln resulted in a
      destabilization of the transition state by about 1.7 kcal mol-1. These results
      indicate that His-452, which is a possible proton acceptor/donor in human E3
      reaction, is critical to human E3 catalysis and that the local environment around
      His-452 and Glu-457, which are suggested to be hydrogen-bonded, is important in
      the binding of dihydrolipoamide to the enzyme.

PMID- 1347529
TI  - Identification and biochemical characterization of novel putative substrates for
      the epidermal growth factor receptor kinase.
AB  - To gain insight into the mechanisms which control the mitogenic response to
      epidermal growth factor (EGF), we have partially purified and characterized
      several intracellular proteins which are phosphorylated on tyrosine residues
      following activation of the epidermal growth factor receptor (EGFR). Partial
      purification was achieved by immunoaffinity chromatography using immobilized anti
      phosphotyrosine antibodies. Antisera generated against the partially purified
      proteins were used to identify at least five novel EGFR putative substrates,
      designated, on the basis of their apparent molecular weight, p97, p68, p61, p56,
      and p23. All of these proteins became specifically phosphorylated on tyrosine
      after EGF treatment of intact cells, as assessed by phosphoamino acid analysis,
      and none of them represented an EGFR degradation product. The phosphorylation of
      these proteins appeared to be relatively specific for the EGFR. In particular, an
      EGFR-related kinase, erbB-2 was much less efficient than EGFR at phosphorylating
      p97, p56, and p23 and incapable of phosphorylating p68. The identification of
      these novel EGFR putative substrates should lead to a better understanding of the
      mechanisms controlling the specificity of EGFR-mediated mitogenic signaling.

PMID- 1347531
TI  - Isolation and characterization of the acetyl-CoA synthetase from Penicillium
      chrysogenum. Involvement of this enzyme in the biosynthesis of penicillins.
AB  - Acetyl-CoA synthetase (ACS) of Penicillium chrysogenum was purified to
      homogeneity (745-fold) from fungal cultures grown in a chemically defined medium
      containing acetate as the main carbon source. The enzyme showed maximal rate of
      catalysis when incubated in 50 mM HCl-Tris buffer, pH 8.0, at 37 degrees C. Under
      these conditions, ACS showed hyperbolic behavior against acetate, CoA, and ATP;
      the Km values calculated for these substrates were 6.8, 0.18, and 17 mM,
      respectively. ACS recognized as substrates not only acetate but also several
      fatty acids ranging between C2 and C8 and some aromatic molecules (phenylacetic,
      2-thiopheneacetic, and 3-thiopheneacetic acids). ATP can be replaced by ADP
      although, in this case, a lower activity was observed (37%). ACS in inhibited by
      some thiol reagents (5,5'-dithiobis(nitrobenzoic acid), N-ethylmaleimide, p
      chloromercuribenzoate) and divalent cations (Zn2+, Cu2+, and Hg2+), whereas it
      was stimulated when the reaction mixtures contained 1 mM dithiothreitol, reduced
      glutathione, or 2-mercaptoethanol. The calculated molecular mass of ACS was 139
      +/- 1 kDa, and the native enzyme is composed of two apparent identical subunits
      (70 kDa) in an alpha 2 oligomeric structure. ACS activity was regulated "in vivo"
      by carbon catabolite inactivation when glucose was taken up by cells in which the
      enzyme had been previously induced. This enzyme can be coupled "in vitro" to acyl
      CoA:6-aminopenicillanic acid acyltransferase from P. chrysogenum, thus allowing
      the reconstitution of the functional enzymatic system which catalyzes the two
      latter reactions responsible for the biosynthesis of different penicillins. The
      ACS from Aspergillus nidulans can also be coupled to 6-aminopenicillanic acid
      acyltransferase to synthesize penicillins. These results strongly indicate that
      this enzyme can catalyze the activation (to their CoA thioesters) of some of the
      side-chain precursors required in these two fungi for the production of several
      penicillins. All these data are reported here for the first time.

PMID- 1347530
TI  - Cloning and characterization of the P subunit of glycine decarboxylase from pea
      (Pisum sativum).
AB  - A pea leaf cDNA library constructed in lambda gt11 was screened with an antibody
      raised to the P subunit of glycine decarboxylase. One of the positive clones
      isolated was sequenced and shown to contain an open reading frame, which encoded
      the entire P subunit polypeptide. Aligning the deduced amino acid sequence with
      the amino acid sequence determined directly from the NH2 terminus of the mature P
      subunit shows the presence of a putative 86 amino acid leader sequence,
      presumably required for import into the mitochondria, and gives a Mr of the
      mature protein of 105,000. Comparison of this deduced amino acid sequence with
      the sequence of a pyridoxal phosphate-containing peptide isolated from the P
      subunit of chicken liver glycine decarboxylase shows remarkable conservation. The
      P subunit, however, shows little sequence homology with other published amino
      acid decarboxylases. Expression of the P subunit mRNA shows a pattern very
      similar to that of the corresponding polypeptide: it is strongly light induced
      and is expressed at a much higher level in leaves than in other tissues. Southern
      blot analysis suggests that the P subunit is encoded by a small multigene family.

PMID- 1347532
TI  - Identification of two molecular defects in a child with leukocyte adherence
      deficiency.
AB  - Children with leukocyte adherence deficiency (LAD), or leukocyte cell adhesion
      molecule deficiency, experience recurrent, life-threatening bacterial infections
      related to severe deficiency in surface expression of the leukocyte integrin
      molecules. The leukocyte integrins consist of a common CD18 (beta) subunit and
      individual, noncovalently associated alpha subunits designated CD11a, CD11b, and
      CD11c. Defects in the CD18 subunit prevent surface expression of the CD11/CD18
      complexes in children with this disease. We investigated the molecular basis of
      the disease in a child with the severe deficiency form of LAD and identified two
      molecular defects in the CD18 subunit. The first defect is a single-base pair C--
      -T transposition resulting in an amino acid substitution of a leucine for a
      proline at amino acid 178. This amino acid substitution is located in a region
      that is highly conserved among the integrin beta subunits and where two previous
      defects have been located in LAD. The second mutation involves a deletion of 220
      base pairs in the cDNA coding for a portion of the extracellular domain and
      results in a frameshift into a premature stop codon. The deleted region
      corresponds to a single exon in the CD18 gene. Identification of these two
      molecular defects in a single child with this disease indicates the compound
      heterozygous nature of the disorder in this child and identifies regions of the
      CD18 subunit that may be important for CD11/CD18 heterodimer formation and
      surface expression.

PMID- 1347533
TI  - High-carbohydrate, low-fat diet? Negative.
AB  - Triglyceride levels rise with increased carbohydrate intake, according to a long
      term study of normal children from several countries. Moreover, carbohydrate
      raises blood glucose levels and insulin requirements.

PMID- 1347534
TI  - Is tight blood sugar control effective and justified? Affirmative.
AB  - Continuous subcutaneous insulin infusion can delay progression of both
      retinopathy and nephropathy. In fact, very few insulin-dependent patients
      developed clinical renal disease while on this treatment.

PMID- 1347535
TI  - Tight glycemic control? Negative.
AB  - Many poorly controlled patients do not develop proliferative retinopathy and
      nephropathy, whereas some tightly controlled patients do. In any event,
      normalization of blood glucose may be impossible and dangerous.

PMID- 1347536
TI  - Are oral hypoglycemic agents likely to benefit NIDDM patients? Affirmative.
AB  - The sulfonylureas may prevent progression from impaired glucose tolerance to
      diabetes as well as control hyperglycemia. Patient response depends on the
      physiologic status of insulin secretion and effectiveness, however.

PMID- 1347537
TI  - Oral hypoglycemic agents? Negative.
AB  - I am convinced that oral hypoglycemic therapy is associated with increased
      cardiovascular mortality. But the more important issue is whether the benefits of
      these agents are worth the risk.

PMID- 1347538
TI  - 'Syndrome X': is it a significant cause of hypertension? Affirmative.
AB  - A number of biologic actions of insulin lend credence to the hypothesis that
      insulin resistance can produce hypertension, perhaps by stimulating a
      hyperkinetic circulation. But it may do so only in lean individuals.

PMID- 1347539
TI  - Syndrome X: a cause of hypertension? Negative.

PMID- 1347540
TI  - Glycosylation of proteins and microangiopathy.
AB  - Diabetic complications may result from chronic glycosylation of protein within
      cells and in the extracellular matrix. Prevention of glycosylation with
      aminoguanidine has forestalled complications in experimental diabetes.

PMID- 1347541
TI  - Proteinuria and microalbuminuria as predictors of nephropathy.
AB  - Measurement of proteinuria, microalbuminuria, and sodium-lithium countertransport
      in red cells has no practical value. A low-protein diet and ACE inhibitor therapy
      are currently the best way to retard progression of diabetic renal disease.

PMID- 1347542
TI  - Lipoprotein abnormalities in diabetes mellitus.
AB  - In most diabetic patients, insulin or sulfonylurea treatment also resolves the
      characteristic triglyceride elevation. However, patients with central obesity or
      familial hypertriglyceridemia may require a lipid-lowering drug.

PMID- 1347543
TI  - Protein-bound glucose as a screening test for diabetes.

PMID- 1347544
TI  - Should NIDDM patients be on high-carbohydrate, low-fat diets? Affirmative.
AB  - Most diet studies are too short, capturing only the temporary rise in
      triglycerides after a high-carbohydrate, low-fat diet is begun. Over time,
      triglycerides and total cholesterol will fall while HDL cholesterol is
      maintained.

PMID- 1347545
TI  - Psychotic (delusional) depression: a meta-analysis of physical treatments.
AB  - Literature reviews have suggested that combination antidepressant/antipsychotic
      drug therapy and electroconvulsive therapy (ECT) are of comparable efficacy in
      treating psychotic depression, and distinctly superior to antidepressant alone or
      antipsychotic alone. We undertook a meta-analysis of 44 studies, and focussed on
      those three principal treatment options. There was a trend for ECT to be superior
      to combination drug therapy, with bilateral ECT being suggested as distinctly
      more effective than unilateral, and ECT was demonstrated to be significantly
      superior to tricyclic drug alone. Combination drug therapy ranked as more
      effective than antipsychotic alone and than antidepressant alone, but that
      greater efficacy was not significant.

PMID- 1347546
TI  - The effect of a selective alpha 2-adrenergic receptor antagonist (midaglizole) on
      the cyclic 3',5'-adenosine monophosphate production in human mononuclear cells.
AB  - A selective alpha 2-adrenergic antagonist, midaglizole, has been recently
      reported to have efficacy in patients with asthma. To understand the mechanisms,
      we investigated the effect of midaglizole on the cyclic 3', 5'-adenosine
      monophosphate (cAMP) production in human mononuclear cells (MNCs). MNCs were
      separated by a histopaque gradient from 10 normal subjects and 10 subjects with
      asthma. cAMP was measured by RIA kits. Midaglizole (10 mumol/L) significantly
      enhanced isoproterenol-induced cAMP production in both groups, although
      midaglizole (from 1 to 100 mumol/L) did not increase the cAMP production by
      itself. The percent increase in cAMP was more in subjects with asthma (183.8%)
      than in normal subjects (140.4%); however, the absolute increase was not
      different. Platelet-activating factor has been demonstrated to inhibit beta
      agonist-induced cAMP production in several mammalian tissues, including human
      MNCs. Midaglizole also prevented platelet-activating factor-induced
      desensitization of the cAMP response to isoproterenol in MNCs. These findings
      suggest that midaglizole may be a useful additional agent for the therapy of
      bronchial asthma through an enhancement of the cAMP production.

PMID- 1347547
TI  - Stimulation of human naive and memory T helper cells with bacterial superantigen.
      Naive CD4+45RA+ T cells require a costimulatory signal mediated through the LFA
      1/ICAM-1 pathway.
AB  - The role of the accessory molecule ICAM-1 in activation of subpopulations of
      human T cells was examined using the bacterial superantigen staphylococcal
      enterotoxin A (SEA) as a MHC class II and TCR-dependent polyclonal T cell
      activator. Human T cells responded with different sensitivity to SEA when
      presented on mouse accessory cells expressing a human transfected MHC class II
      gene product. Mouse L cells cotransfected with both MHC class II (DR2A or DR7)
      and ICAM-1-stimulated T cells at 100-fold lower concentrations of SEA as compared
      to the single transfected cells. mAb reacting with the CD11a, CD18, or ICAM-1
      molecules efficiently inhibited T cell activation with the cotransfected HLA
      DR2A/ICAM-1 cell but did not influence T cell activation with the HLA-DR2A single
      transfected cell. Analysis of the ICAM-1 requirement on CD4+ memory (CD4+45RO+)
      and naive (CD4+45RA+) T cells revealed that CD4+45RA+ naive Th cells were
      hyporesponsive to SEA-induced activation with the HLA-DR2A single transfectant.
      However, cotransfection of ICAM-1 enabled these cells to respond to low doses of
      SEA implicating that they are more dependent on accessory molecules than the
      CD4+45RO+ cells. rICAM-1 immobilized on a plastic surface, was able to strongly
      costimulate SEA-induced T cell activation with the HLA-DR2A single transfectant,
      suggesting that costimulatory signals mediated to the T cells through LFA-1 can
      be delivered physically separated from the TCR signal. CD4+45RO+ memory and
      CD4+45RA+ naive Th cells apparently differ in their capacities to be activated by
      SEA bound to HLA-DR. Although the TCR molecule densities are similar in these two
      subsets, costimulation with ICAM-1 is required for activation of the CD4+45RA+,
      but not the CD4+45RO+ T cell subset at 1 to 10,000 ng/ml concentrations of SEA.
      This observation indicates different activation thresholds of naive and memory Th
      cells when triggering the TCR over a wide dose interval of superantigen.

PMID- 1347548
TI  - Transforming growth factor-beta directs IgA switching in human B cells.
AB  - Transforming growth factor (TGF)-beta added to cultures of highly purified human
      splenic B cells induced high levels of IgA synthesis in the presence of PWM and
      activated cloned CD4+ T cells. TGF-beta had no effect on IgM or IgG production.
      The induction of IgA synthesis by TGF-beta reflected IgA switching, because a
      strong induction of IgA production was also observed, when sIgA- B cells were
      cocultured with cloned activated CD4+ T cells in the presence of pokeweed
      mitogen. Resting CD4+ T cell clones or activated CD8+, TCR-gamma delta + CD4-,CD8
      T cell clones failed to provide the co-stimulatory signal that in addition to
      TGF-beta and pokeweed mitogen was required for induction of IgA switching and IgA
      synthesis. mAb against CD4 or class II MHC molecules inhibited TGF-beta induced
      IgA synthesis, indicating that CD4-class II MHC interactions are required for
      productive T-B cell contacts resulting in IgA production. In contrast, anti-LFA
      1, anti-CD2, and anti-class I MHC mAb were ineffective. TGF-beta failed to induce
      IgA synthesis by sIgA+ B cells under these culture conditions. Interestingly,
      induction of IgA production by sIgA- B cells required neutralization of TGF-beta
      activity by addition of the anti-TGF-beta mAb 1D11.1G 24 h after onset of the
      cultures. IgA production was prevented when the anti-TGF-beta mAb was added at
      the start of the cultures, indicating the specificity of the reaction. IgA
      synthesis was completely suppressed when TGF-beta was present during the total
      culture period of 11 days. These findings indicate that TGF-beta can act as a
      specific switch factor for IgA, provided it is only present at early stages of
      the cultures.

PMID- 1347549
TI  - Molecules involved in the adhesion and cytotoxicity of activated monocytes on
      endothelial cells.
AB  - Our study was designed to investigate the surface molecules involved in the
      adhesion and cytotoxicity of activated human monocytes on resting and IL-1
      stimulated endothelial cells (EC). Monocytes, exposed to the prototypic
      activating stimuli IFN-gamma and LPS, showed increased binding to resting and IL
      1-treated EC. Activated monocytes were cytotoxic for resting and IL-1-treated EC
      in a 24- to 48-h [3H]TdR release assay. Anti-CD18 mAb significantly inhibited
      binding of monocytes on EC: in particular they caused 59 and 22% inhibition of
      adhesion of activated monocytes to resting and IL-1-stimulated EC, respectively.
      Anti-VLA4 mAb had little or no effect on binding when used alone, but combined
      use with anti-CD18 revealed an important role for this adhesion pathway: in
      particular, VLA4-dependent adhesion accounted for 40% of the binding of activated
      monocytes on IL-1-treated EC. Anti-CD18 mAb caused similar inhibition (77 and
      81%) of the cytotoxicity of activated monocytes on resting and IL-1-treated EC in
      spite of the fact that this pathway accounted for only 22% of binding to
      activated EC. Moreover, anti-VLA4 mAb, alone or in combination with anti-CD18,
      had no effect on cytotoxicity. These results suggest that adhesion of activated
      monocytes to activated EC involves the CD18- and VLA4-dependent pathways, but
      that the former is dominant for the expression of cytotoxicity. Thus, in the
      ensemble of adhesion molecules available for interaction between endothelium and
      activated monocytes, the hierarchy of their importance may vary for different
      functions.

PMID- 1347550
TI  - Transforming growth factor-beta enhances the in vivo effector function and memory
      phenotype of antigen-specific T helper cells in experimental autoimmune
      encephalomyelitis.
AB  - Transforming growth factor-beta (TGF-beta) had a profound effect on the in vitro
      phenotypic development of Ag-activated Th cells and enhanced the in vivo effector
      function of these cells upon adoptive transfer. Previous studies have shown that
      there are two types of Th cell populations found in unimmunized animals, naive
      helper cells, which are short-lived and express low levels of CD44 and high
      levels of CD45R and Mel-14, and memory helper cells, which have a long life span
      and express high levels of CD44 and low levels of CD45R and Mel-14. Culturing of
      Ag-specific murine Th cell lines and clones in the presence of TGF-beta greatly
      enhanced both the memory phenotype of the cultured cells and the effector
      function upon adoptive transfer in experimental autoimmune encephalomyelitis.
      Histologic evaluation of spinal cords from recipients receiving passively
      transferred murine T cell lines cultured with TGF-beta revealed large
      demyelinated plaques (multiple sclerosis-like) that were not present in animals
      receiving cells cultured with Ag alone. TGF-beta also enhanced the capability of
      myelin basic protein-specific Lewis rat T cell lines to transfer experimental
      autoimmune encephalomyelitis and potentiated a purified protein derivative
      specific rat helper cell line to transfer delayed type hypersensitivity. Thus,
      the effects of TGF-beta did not appear to be limited by species specificity, Ag
      specificity, or in vivo T cell function. This is the first study showing that TGF
      beta can potentiate the development and maintenance of the Th cell memory
      phenotype in vitro and enhance their in vivo effector function in an animal
      disease model.

PMID- 1347551
TI  - Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and
      inhibited via adenosine A2 receptors.
AB  - We have recently demonstrated that human neutrophils (PMN) possess two different
      classes of adenosine receptors (A1 and A2) that, when occupied, promote
      chemotaxis and inhibit the generation of reactive oxygen species (e.g., O2- and
      H2O2), respectively. We have previously demonstrated that adenosine protects
      endothelial cells (EC) from injury by stimulated neutrophils (PMN) both by
      diminishing generation of H2O2 and inhibiting adherence of PMN to EC. We
      therefore determined whether occupancy of A1 or A2 adenosine receptors regulated
      adherence of PMN to EC. At concentrations similar to those required to inhibit
      release of O2- by ligation of A2 receptors, both adenosine (IC50 = 56 nM) and 5'N
      ethylcarboxamidoadenosine (NECA, IC50 = 8 nM), the most potent A2 agonist,
      inhibited adherence to EC by stimulated PMN (FMLP, 0.1 microM). In direct
      contrast, the specific A1 agonists N6-phenylisopropyladenosine and N6
      cyclopentyladenosine (CPA) promoted PMN adherence to EC at concentrations of 1
      100 nM. To further investigate the mechanisms by which adenosine receptor
      agonists affected the adherence of stimulated PMN we examined the effect of NECA
      (A2) and CPA (A1) on the adherence of PMN to fibrinogen (a ligand for the beta 2
      integrin CD11b/CD18) and to gelatin. In a dose-dependent manner (IC50 = 2 nM),
      NECA inhibited the adherence of FMLP-treated PMN to fibrinogen- but not gelatin
      coated plates. In contrast, CPA (A1) promoted adherence of stimulated PMN to
      gelatin-(EC50 = 13 pM) but not fibrinogen-coated plates. Theophylline (10
      microM), an adenosine receptor antagonist, reversed the inhibition by NECA (0.3
      microM) of stimulated neutrophil adherence to fibrinogen. These observations not
      only confirm the presence of A1 and A2 receptors on PMN but also suggest two
      opposing roles for adenosine in inflammation. Occupancy of A1 receptors promotes
      neutrophil adherence to endothelium and chemotaxis (a proinflammatory role)
      whereas occupancy of A2 receptors inhibits adherence and generation of toxic
      oxygen metabolites (an antiinflammatory role).

PMID- 1347552
TI  - Zymosan-stimulated tumor necrosis factor-alpha production by human monocytes.
      Down-modulation by phorbol ester.
AB  - In this study, we showed that human monocytes produced TNF-alpha in response to
      zymosan, a particulate agonist. Protein kinase C (PKC) seems to play a regulatory
      role in zymosan-induced TNF-alpha secretion. The pretreatment of monocytes with
      PMA induced a dose-dependent inhibition of zymosan-stimulated TNF production.
      This inhibition was likely due to an activation of PKC because it was prevented
      by inhibitors of PKC, sphingosine, and staurosporine. Moreover, PMA elicited a
      profound down-modulation of zymosan binding to monocytes. The inhibition of
      zymosan binding and TNF production displayed similar dose-dependence, suggesting
      that both events were closely related. In addition, PMA did not modify the
      expression of CD11b/CD18 receptor that is involved in zymosan recognition. In
      view of these findings, qualitative changes of CD11b/CD18 molecules might account
      for the inhibition of zymosan binding and TNF production. Thus, PMA specifically
      increased the association of CD11b/CD18 with the detergent-insoluble
      cytoskeleton. Cytochalasin B but not microtubule disrupters, nocodazole and
      colchicine, partially prevented the inhibition of zymosan binding. Hence, the
      inhibitory action of PMA on zymosan binding seems to be mediated by an increase
      in attachment of zymosan receptor to cytoskeleton and more likely to
      microfilaments. The regulatory activity of PKC might represent a first way of
      limiting cytokine over-production in response to pathogens which interact with
      monocytes via CD11/CD18 molecules.

PMID- 1347553
TI  - CD4+ Th2 response induced by Schistosoma mansoni eggs develops rapidly, through
      an early, transient, Th0-like stage.
AB  - Data from recent studies of murine schistosomiasis mansoni have indicated that
      certain characteristics of this infection, such as eosinophilia and elevated IgE,
      are due largely to the induction of Th2-like immune responses by parasite ova.
      The present study was designed to examine more closely the genesis and
      development of these skewed Th responses to schistosome eggs. Accordingly, eggs
      isolated from infected mice were injected s.c. into normal mice. After
      inoculation, draining lymph node (LN) cells were recovered, phenotyped, and
      tested for their ability to proliferate and secrete IL-2 and IFN-gamma (as
      markers of Th1 function) and IL-4, IL-5, and IL-10 (Th2 cytokines). The results
      show a maximal LN enlargement of 40- to 100-fold by day 3 after egg inoculation.
      The CD4/CD8/B cell ratio at this time is similar to that in LN from normal mice,
      but increases in numbers of cells expressing very low levels of MEL-14 and high
      levels of Pgp-1 are evident by days 3 and 10, respectively. Surprisingly, the
      initial detectable Ag-specific response to schistosome eggs, observed at day 1,
      is the production of IFN-gamma. By day 3, LN cells are capable of proliferating
      and making IFN-gamma plus IL-2, IL-4, IL-5, and IL-10 when stimulated with
      soluble egg Ag and, therefore, appear Th0-like. After 7 to 10 days, IFN-gamma
      production is severely depressed but the response continues to be characterized
      by IL-4, IL-5, IL-10, and IL-2. Depletion studies indicate that CD4 cells are the
      major population responsible for Ag-mediated proliferation and cytokine
      production. Results show that schistosome eggs are autonomous inducers of
      vigorous Th2-like effector responses. Further, our data, from a system that
      utilizes an in vivo priming step, support the contentions that skewed Th
      responses develop via an intermediate Th0 stage is accompanied by a loss of the
      MEL-14 surface marker and an increase in Pgp-1 expression.

PMID- 1347554
TI  - Regulation of germ-line epsilon transcription and induction of epsilon switching
      in cloned EBV-transformed and malignant human B cell lines by cytokines and CD4+
      T cells.
AB  - IL-4 induces germ-line epsilon transcript synthesis in normal human B cells, but
      a second signal provided by CD4+ T cells is required for subsequent production of
      productive epsilon mRNA and IgE synthesis. In the present study we demonstrate
      that IL-4 specifically induces germ-line epsilon transcripts in most EBV
      lymphoblastoid (LCL) and EBV+ and EBV- Burkitt's lymphoma (BL) cells without
      inducing IgE synthesis. However, cocultivation of cloned sIgM+, sIgE- EBV-LCL or
      BL cells with activated CD4+ T cell clones in the presence of IL-4 resulted in
      IgE production in 13 to 24% of the wells. Analysis of rearranged DNA in IgE
      producing cloned BL cells indicated that epsilon switching occurred through a
      recombination deletion event. IgE production is a stable feature of the cloned
      switched EBV-LCL and BL cells because these cells continued to produce relatively
      high levels of IgE in the absence of IL-4 and CD4+ T cells. Induction of IgE
      synthesis was blocked by IFN-gamma, IFN-alpha, and transforming growth factor
      beta (TGF-beta), but only TGF-beta inhibited IL-4-induced germ-line epsilon mRNA
      expression. These results suggest that the inhibitory effects of TGF-beta are
      mediated via inhibition of germ-line epsilon expression, whereas IFN-alpha and
      IFN-gamma block other steps in the regulatory processes resulting in induction of
      IgE synthesis by established human B cell line cells. Our results indicate that
      the same set of signals that induce normal B cells to switch to IgE synthesis
      also induce high frequency epsilon switching in cloned established EBV
      transformed and malignant B cell lines including classical cell lines such as JY
      and BL-2.

PMID- 1347555
TI  - Modulation of intercellular adhesion molecule-1 expression on human melanocytes
      and melanoma cells: evidence for a regulatory role of IL-6, IL-7, TNF beta, and
      UVB light.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is involved in cell-cell interactions
      of leukocytes and parenchymal cells and thus plays an important role in
      immunologic and inflammatory reactions. The expression of ICAM-1 that is found on
      many different cells such as melanocytes and melanoma cells is induced by various
      cytokines, including interferon-gamma (IFN gamma), interleukin (IL)-1 and tumor
      necrosis factor alpha (TNF alpha). Because expression of ICAM-1 in melanoma was
      found to correlate with increased risk of metastasis, the regulation of ICAM-1
      expression on human melanocytes and melanoma cells was investigated. Foreskin
      derived melanocytes and melanoma cell lines (A375, G361) were incubated with
      different cytokines and ICAM-1 expression was evaluated by fluorescence-activated
      cell sorter. IFN gamma, IL-1, IL-7, TNF alpha, and TNF beta significantly
      upregulated ICAM-1 expression in a dose-dependent manner. Most interestingly, the
      cytokine IL-6, which does not influence adhesion-molecule expression on other
      cells, significantly upregulated melanocyte and melanoma cell ICAM-1 expression.
      This effect was dose dependent and could be blocked by an IL-6 antibody.
      Irradiation with ultraviolet (UVB) light did not influence constitutive ICAM-1
      expression on melanoma cells and melanocytes, but suppressed cytokine-induced
      ICAM-1 expression when cells were harvested 16 h after irradiation. These
      findings were further confirmed by Northern blot analysis, showing a marked
      accumulation of ICAM-1 mRNA after cytokine treatment, which was reduced by
      irradiation with UVB light. However, when UVB-exposed melanoma cells were
      cultured for at least 48 h induction of ICAM-1 expression was observed. These
      data indicate that, similar to other cells, ICAM-1 expression on melanoma cells
      and melanocytes is regulated by cytokines and that UVB light affects ICAM-1
      expression on melanocytic cells in a biphasic manner.

PMID- 1347556
TI  - Expression of keratinocyte transglutamine mRNA revealed by in situ hybridization.
AB  - Plasma membrane-bound transglutaminase (TGm) catalyzes the formation of cornified
      envelopes (CE) in terminally differentiating keratinocytes. The recent cloning of
      cDNA encoding rabbit TGm allows detailed studies of its gene expression and
      regulation. In the present paper, we describe the localization of TGm mRNA in
      rabbit tissues, as well as in normal and psoriatic human skin, as assessed by in
      situ hybridization. Furthermore, we correlate TGm mRNA localization with the
      distribution of the TGm protein detected by immunohistochemistry with a specific
      monoclonal antibody. In rabbit epidermis, TGm mRNA was expressed in suprabasal
      cells. The TGm protein was detected in the upper stratum spinosum and stratum
      granulosum. In rabbit esophagus, TGm mRNA and protein were already expressed to a
      high level in the first suprabasal cell layer, and their expression decreased in
      the more differentiated cells. In normal human skin, a small amount of TGm mRNA,
      restricted to the stratum granulosum, was found, whereas psoriatic skin samples
      contained high amounts of TGm mRNA in the suprabasal layers with a decreasing
      gradient into the rete ridges, i.e., the involutions of the epidermis into the
      dermal compartment. The TGm protein was absent from the rete ridges and confined
      to several cell layers expressing high levels of mRNA. There was virtually no
      difference between uninvolved psoriatic and normal epidermis.

PMID- 1347557
TI  - [Immunohistochemical study of proliferating cell nuclear antigen (PCNA) in
      gynecological tumors and their related lesions].
AB  - We have investigated whether monoclonal antibody (PC10) of proliferating cell
      nuclear antigen (PCNA) could be useful as a marker of proliferating cells within
      formalin-fixed, paraffin-embedded tissue sections of 140 gynecological tumors and
      their related lesions. There was a positive correlation (r = 0.76) between the
      labelling index for PCNA and that for Ki67. Immunohistochemical staining for PC10
      was confined to the nucleus and showed a diffuse or granular pattern or a mixture
      of both. The distribution of PC10 staining in non-neoplastic tissues was
      localized to proliferating cell compartments. In malignant tissues, the
      localization of the distribution of PCNA-positive cells came to be lost and the
      proportion of positive cells varied from case to case as well as from field to
      field within the same tissue section. The cases in which more than 31% of cells
      were positive for PCNA were as follows: Cervical squamous dysplasia 2/3, squamous
      carcinoma in situ 2/5, microinvasive squamous carcinoma 2/2, invasive squamous
      carcinoma 9/13, adenocarcinoma in situ 4/4, microinvasive adenocarcinoma 3/3,
      invasive adenocarcinoma 6/7, endometrial adenocarcinoma 6/25, ovarian epithelial
      malignant tumors 11/17, sex cord stromal tumors 2/14, and germ cell tumors 3/22.
      It is concluded that immunohistochemical staining for PC10 may be useful as a
      marker for proliferating activity of the cells both in normal and tumor tissues
      rather than for malignancy.

PMID- 1347558
TI  - Comparison of hantavirus isolates using a genus-reactive primer pair polymerase
      chain reaction.
AB  - RNA of more than 40 hantavirus isolates, originating from rodents and humans of
      widely separated geographical areas, was copied to cDNA using reverse
      transcriptase and amplified by polymerase chain reaction (PCR). A genus-reactive
      oligonucleotide primer pair, flanking a 365 bp region of the G2 glycoprotein
      gene, was chosen for genus-reactive PCR. DNA products were digested with 20
      restriction endonucleases and cleavage patterns were analysed. For strains of
      known sequence, the restriction patterns observed were consistent with those
      predicted from sequence data, demonstrating that the amplified products
      originated from target virus RNA. Further analyses suggested that all amplified
      viruses could be easily typed into one of five restriction patterns using only
      five enzymes. The categories identified by restriction analysis of PCR-amplified
      cDNA corresponded with serogroups established by plaque-reduction neutralization
      tests. This method may greatly simplify the identification of new hantavirus
      isolates.

PMID- 1347559
TI  - Cell-specific alternative RNA splicing of an FMRFamide gene transcript in the
      brain.
AB  - Individual neurons synthesize different peptide neurotransmitters and
      neuromodulators. In general, specificity is achieved by transcriptional
      regulation of neuropeptide-encoding genes. In Lymnaea, the FMRFamide and
      GDP/SDPFLRFamide neuropeptides are encoded by separate exons. Here we provide
      evidence that the two exons are part of the same gene and that in neurons
      expressing the gene the two exons are spliced onto a common upstream exon
      encoding a hydrophobic leader sequence. In addition, in situ hybridization data
      show that there is mutually exclusive cytoplasmic expression of each of the
      neuropeptide-encoding exons. Thus, differential neuropeptide synthesis is likely
      to be regulated by an alternative splicing mechanism. The cellular specificity of
      these splicing events is remarkable and suggests that cell-specific alternative
      splicing may be of major importance in establishing neuronal diversity in this
      system.

PMID- 1347560
TI  - Beta-adrenergic receptors: astrocytic localization in the adult visual cortex and
      their relation to catecholamine axon terminals as revealed by electron
      microscopic immunocytochemistry.
AB  - It has long been recognized that noradrenaline, the most abundant catecholamine
      within the visual cortex, plays important roles in modulating the sensitivity of
      cortical neurons to visual stimuli. However, whether or not these noradrenaline
      effects are confined to a discrete synaptic specialization or mediated by diffuse
      modulation of a group of synapses has remained an issue open for debate. The aim
      of this study was to examine the cellular basis for noradrenaline action within
      the visual cortex of adult rats and cats. To this end, I used electron
      microscopic immunocytochemistry to examine the relationship between (1)
      catecholamine axon terminals and beta-adrenergic receptors (beta AR), which,
      together, may define the effective sphere of noradrenaline modulation; and then
      (2) these putative sites for catecholamine modulation and axospinous asymmetric
      junctions where excitatory neurotransmission is likely to dominate. Antibodies
      against beta AR were used at light and electron microscopic levels on the visual
      cortex of rat and cat. Rat visual cortex was also labeled simultaneously for beta
      AR and the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), to
      determine the ultrastructural relationships between catecholamine terminals and
      beta AR. Immunoperoxidase labeling revealed that beta AR404, a polyclonal
      antibody directed against the C-terminal tail of hamster lung beta AR (beta 2
      type), recognized astrocytic processes predominantly. In contrast, beta AR248, a
      polyclonal antibody directed against the third cytoplasmic loop, recognized
      neuronal perikarya as observed in previous studies. Dual labeling for beta AR404
      and TH revealed that catecholamine axon terminals that contained numerous
      vesicles formed direct contacts with astrocytic processes exhibiting beta AR404
      immunoreactivity. However, some catecholamine axon terminals that lacked dense
      clusters of vesicles were positioned away from beta AR404-immunoreactive
      astrocytes. Frequently, beta AR-immunoreactive astrocytic processes surrounded
      asymmetric axospinous junctions while also contacting catecholamine axon
      terminals. These observations support the possibility that, through activation of
      astrocytic beta AR, noradrenaline modulates astrocytic uptake mechanism for
      excitatory amino acids, such as L-glutamate. Astrocytic beta AR might also define
      the effective sphere of catecholamine modulation through alterations in the
      morphology of distal astrocytic processes and the permeability of gap junctions
      formed between astrocytes.

PMID- 1347561
TI  - Proctolin activates an inward current whose voltage dependence is modified by
      extracellular Ca2+.
AB  - The pentapeptide proctolin modulates the activity of the rhythmic pattern
      generators in the crustacean stomatogastric nervous system. Proctolin strongly
      excites the lateral pyloric and the inferior cardiac neurons of the
      stomatogastric ganglion (STG), causing them to fire extended high-frequency
      bursts of action potentials (Hooper and Marder, 1987; Nusbaum and Marder,
      1989a,b). We now report that proctolin depolarizes these cells maximally at
      membrane potentials close to the threshold for action potential generation. In
      voltage clamp, proctolin evokes an inward current, carried at least partially by
      Na+, that shows strong outward rectification. Removal of extracellular Ca2+
      markedly increases the amplitude of the proctolin-evoked current and linearizes
      its current-voltage curve. The properties of the proctolin current make it
      ideally suited to contribute to the activity-dependent modulation of the pyloric
      network of the STG.

PMID- 1347562
TI  - Extinction of fear-potentiated startle: blockade by infusion of an NMDA
      antagonist into the amygdala.
AB  - Data derived from in vitro preparations indicate that NMDA receptors play a
      critical role in synaptic plasticity in the CNS. More recently, in vivo
      pharmacological manipulations have suggested that an NMDA-dependent process may
      be involved in specific forms of behavioral plasticity. All of the work thus far
      has focused on the possible role of NMDA receptors in the acquisition of
      responses. However, there are many examples in the behavioral literature of
      learning-induced changes that involve the reduction or elimination of a
      previously acquired response. Experimental extinction is a primary example of the
      elimination of a learned response. Experimental extinction is well described in
      the behavioral literature, but has not received the same attention in the
      neurobiological literature. As a result, the neural mechanisms that underlie this
      important form of learning are not at all understood. In the present experiments,
      the fear-potentiated startle paradigm was employed to begin to investigate neural
      mechanisms of extinction. The results show that infusion of the NMDA antagonist
      D,L-2-amino-5-phosphonovaleric acid (AP5) into the amygdala, a limbic structure
      known to be important for fear conditioning, dose-dependently blocked extinction
      of conditioned fear. Control experiments showed that the blockade of extinction
      was neither the result of the permanent disruption of amygdaloid function nor the
      result of decreased sensitivity of the animals to the conditioned stimulus.
      Infusion of AP5 into the interpositus nucleus of the cerebellum, a control site,
      did not block extinction. Finally, intra-amygdala infusion of a selected dose of
      the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione did not block
      extinction of conditioned fear. These results, together with a previous report
      from our laboratory (Miserendino et al., 1990), demonstrate the importance of the
      amygdala in the elaboration of conditioned fear and suggest that an NMDA
      dependent process might underlie the extinction of conditioned fear.

PMID- 1347563
TI  - Pharmacological discrimination of N-type from L-type calcium current and its
      selective modulation by transmitters.
AB  - GABA and norepinephrine inhibit high voltage-activated calcium current in chick
      sensory neurons. Using specific pharmacological tools, we have dissected this
      current into two components: the major one is omega-conotoxin sensitive and
      dihydropyridine resistant (N-type) while the minor one is dihydropyridine
      sensitively and omega-conotoxin resistant (L-type). The ability to selectively
      eliminate these two components has allowed us to determine whether the
      transmitters target the same or different channel types. Both GABA and
      norepinephrine modulate the N-type component as evidenced by their lack of effect
      on (1) omega-conotoxin-resistant current and (2) pure L-type tail current,
      prolonged by a dihydropyridine calcium channel agonist. This simple
      pharmacological profile will allow future tests of the significance of the two
      channel types in regulating sensory neuron functions.

PMID- 1347564
TI  - Distribution and characterization of different molecular products of pro
      somatostatin in the hypothalamus and posterior pituitary lobe of the Mongolian
      gerbil (Meriones unguiculatus).
AB  - Antisera raised against various synthetic peptide fragments of the pro
      somatostatin molecule were used to visualize immunohistochemically the
      distributions of different pro-somatostatin fragments in the hypothalamus and
      posterior pituitary of the Mongolian gerbil. To define the nature of the
      immunoreactive somatostatin-related molecular forms, gel chromatography combined
      with radioimmunoassays of hypothalamic and posterior pituitary extracts was
      performed. Within the hypothalamus, only trace amounts of somatostatin-28 and
      somatostatin-28(1-12) were present, whereas pro-somatostatin(1-76), pro
      somatostatin(1-64), and somatostatin-14 peptides were present in equimolar
      amounts. In contrast, the posterior pituitary lobe contained equal amounts of
      somatostatin-14, somatostatin-28, and somatostatin-28(1-12) but no pro
      somatostatin(1-76), indicating that pro-somatostatin is further processed during
      the axonal flow to posterior pituitary nerve terminals. The gel chromatographic
      data were further substantiated by immunohistochemical data. Thus, perikarya
      containing all of these five immunoreactivities were strictly confined to the
      periventricular area and parvocellular subset of the paraventricular nucleus.
      However, the number of somatostatin-28- and somatostatin-28(1-12)-immunoreactive
      perikarya was approximately 20% of the number of somatostatin-14- and pro
      somatostatin(1-64)-immunoreactive cells. In other hypothalamic areas only
      somatostatin-14 and pro-somatostatin(1-64) immunoreactivities were detectable in
      cell bodies. These cell bodies were encountered in the organum vasculosum laminae
      terminalis; the suprachiasmatic, ventromedial, arcuate, perifornical, and
      posterior hypothalamic nuclei; and the median preoptic and retrochiasmatic areas.
      In situ hybridization histochemistry revealed that the cellular distribution of
      pro-somatostatin mRNA corresponds to that of somatostatin-14 and pro-somatostatin
      immunoreactivity, suggesting that the immunoreactive material observed within the
      cell bodies is synthetized there and that the differences in density of
      immunoreactivities may be explained by intracellular processing of pro
      somatostatin. Somatostatinergic nerve fibers and terminals in hypothalamic areas
      and the posterior pituitary lobe were immunoreactive to all of the employed
      antisera. From the present results, obvious differences between intrahypothalamic
      and hypothalamo-pituitary somatostatinergic neurons emerge. Within hypothalamic
      neurons not projecting to the median eminence and the posterior pituitary lobe,
      pro-somatostatin is posttranslationally processed in the cell body predominantly
      into pro-somatostatin(1-64) and somatostatin-14. Otherwise, within
      periventricular neurons projecting to the median eminence and the posterior
      pituitary lobe, pro-somatostatin is posttranslationally processed during the
      axonal flow into pro-somatostatin(1-64), somatostatin-14, somatostatin-28, and
      somatostatin-28(1-12).

PMID- 1347565
TI  - Vasopressin modulates cerebrovascular responses to opioids in newborn pigs.
AB  - Vasopressin receptor blockade has been observed to attenuate the systemic
      vascular effects of dynorphin. This study was designed to determine the ability
      of vasopressin to modulate cerebrovascular responses to opioids in newborn pigs
      equipped with closed cranial windows. Topical dynorphin 13 increased pial
      arteriolar diameter during normotension (151 +/- 5, 171 +/- 4, 183 +/- 4 and 187
      +/- 4 microns for control, 10(-10), 10(-8) and 10(-6) M dynorphin 13,
      respectively). During hypotension, however, responses to dynorphin 13 were
      reversed to concentration-dependent decreases in pial arteriolar diameter (184 +/
      3, 169 +/- 4, 165 +/- 4 and 159 +/- 4 microns for control 10(-10), 10(-8) and
      10(-6) M dynorphin 13, respectively). Dynorphin 13-induced pial arteriolar
      dilation was potentiated by the V1 receptor antagonist [1-(beta-mercapto-beta
      beta-cyclopentamethylene propionic acid) 2(o-methyl)-Tyr-AVP] (MEAVP; 5
      micrograms/kg i.v.; 14 +/- 1, 22 +/- 1 and 24 +/- 1% vs. 19 +/- 1, 26 +/- 1 and
      30 +/- 1% increase for 10(-10), 10(-8) and 10(-6) M dynorphin 13 before and after
      MEAVP, respectively). In contrast, dynorphin 13-induced constriction during
      hypotension was markedly reduced by MEAVP (10 +/- 1, 15 +/- 1 and 16 +/- 2% vs. 1
      +/- 1, 4 +/- 1 and 9 +/- 1% decrease for 10(-10), 10(-8) and 10(-6) dynorphin 13
      before and after MEAVP, respectively). Dynorphin 8 and the synthetic kappa-opioid
      selective agonist, U5O,488H, elicited similar tone-dependent responses that were
      modified by MEAVP in a similar fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347566
TI  - Cardiorespiratory effects of the novel opioid analgesic HP 736 in the
      anesthetized dog and conscious goat.
AB  - 7-Bromo-(3a,5-cis)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-pyrrolo[2,3- 6]indol
      5-ol fumarate (HP 736) is a novel opioid analgesic. In vitro, HP 736 displaces
      [3H]dihydromorphine (IC50 = 8.3 x 10(-10) M) and [3H]bremazocine (IC50 = 7.4 x
      10(-8) M) from mu and kappa opioid receptors, respectively, and displays modest
      acetylcholinesterase inhibitory activity (IC50 = 4.0 x 10(-5) M). The in vivo
      antinociceptive activity of HP 736 was found to be comparable to morphine in the
      modified Haffner's tail clip assay in mice and the D'Amour-Smith tail flick assay
      in rats. Moreover, these analgesic effects were found to be completely
      antagonized by the administration of the narcotic antagonist naloxone. A major
      liability of opioid analgesics such as morphine is the potential to cause
      cardiorespiratory depression. HP 736 (2, 4 and 10 mg/kg, i.v.) was found to cause
      significantly less respiratory depression in the anesthetized dog when compared
      to equivalent doses of morphine. At 10 mg/kg, morphine caused a 48% reduction in
      arterial oxygen partial pressure (PaO2) (-42.3 +/- 2.5 mm Hg) and a 52% increase
      in arterial carbon dioxide partial pressure (PaCO2) (21.0 +/- 3.4 mm Hg). In
      contrast, the same dose of HP 736 produced no significant decrease in PaO2, but
      did cause a slight 19% increase in PaCO2 (8.2 +/- 1.3 mm Hg), which was
      significantly less than the response seen after morphine treatment. It was found
      that pretreatment of the dogs with atropine sulfate (1 mg/kg, i.v.) "unmasked"
      the respiratory depressant activity of HP 736 (2 mg/kg, i.v.), indicating that
      the acetylcholinesterase inhibitory activity of the compound may contribute to
      its reduced cardiorespiratory liability. Finally, in confirmatory experiments
      conducted in conscious goats, HP 736 (0.5 mg/kg, i.v.) was found to stimulate
      pulmonary ventilation, increase PaO2 and oxygen consumption (+40%) and decrease
      PaCO2 with an overall stimulatory effect on the metabolic rate. In contrast, the
      same dose of morphine decreased metabolic rate, reduced pulmonary ventilation (
      20%) and PaO2 and increased PaCO2. Overall, the results of these studies indicate
      that HP 736 is a potent opioid analgesic which appears to lack significant
      cardiorespiratory depressant activity.

PMID- 1347568
TI  - Evidence for postjunctional release of ATP evoked by stimulation of muscarinic
      receptors in ileal longitudinal muscles of guinea pig.
AB  - The origin of the ATP release evoked by muscarinic agonists and veratridine from
      longitudinal muscles of the guinea pig was assessed with muscarinic antagonists.
      Acetylcholine (ACh) (1 microM) and bethanechol (10 microM) produced an immediate
      and marked ATP release, which was almost completely blocked by atropine (0.3
      microM) and by the M3 muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine
      methiodide (4-DAMP) (1 microM); release was only slightly affected by
      tetrodotoxin (0.6 microM). The bethanechol-evoked release of ATP was partly, but
      not significantly, inhibited by pirenzepine, a M1 muscarinic antagonist.
      Veratridine, an ACh releaser, also elicited a delayed ATP release, in a
      concentration-related manner. This ATP release was greatly antagonized by
      atropine and by Ca++ removal from the medium, implying mediation by endogenous
      ACh released after depolarization. In contrast, electrically evoked ACh release
      was enhanced by atropine and 4-DAMP. Bethanechol, unlike veratridine, failed to
      elicit measurable ACh release from the tissue. The contraction evoked by
      bethanechol was notably inhibited by atropine and 4-DAMP, but not by pirenzepine
      and AFDX-116, a M2 muscarinic antagonist, at a concentration of 0.3 microM. These
      findings suggest strongly that ATP is postjunctionally released from the ileal
      smooth muscles after stimulation of postsynaptic muscarinic receptors, presumably
      M3 receptors.

PMID- 1347567
TI  - Mechanism of inhibitory effects of azelastine on smooth muscle contraction.
AB  - The mechanism of inhibitory effects of azelastine, an antiallergic and
      antiasthmatic agent, on depolarization- and alpha-1 adrenergic agonist-induced
      contractions of intact smooth muscle was studied. The effects of azelastine on
      membrane currents were determined in isolated guinea pig ileum smooth muscle
      cells with the whole-cell clamp technique; the effects on contraction were
      evaluated in receptor- and G-protein-coupled, alpha-toxin-permeabilized rabbit
      femoral artery and portal vein smooth muscle strips. Azelastine (1-20 microM),
      like dihydropyridines, inhibited spontaneous rhythmic and high K(+)-induced
      contractions, mainly through inhibition of the voltage-dependent (L-type) Ca++
      current. The tonic component of high K+ contractions was inhibited more than the
      phasic component, correlating to voltage-dependent inhibition of Ca++ current by
      the drug. Azelastine (IC50 of 0.25 microM), a known histamine blocker, also
      reversibly inhibited alpha-1 agonist-induced contractions in the presence and
      absence of extracellular Ca++. Both major pathways of pharmacomechanical
      coupling, agonist-induced Ca++ release from the sarcoplasmic reticulum and Ca++
      sensitization of the regulatory/contractile apparatus were blocked by the same
      concentration of drug in permeabilized as in intact muscle. Inositol 1,4,5
      trisphosphate-induced Ca++ release and guanosine 5'-O-(tau-thiotriphosphate)
      induced Ca++ sensitization, however, were not inhibited. Azelastine at high
      (greater than 10 microM) concentrations reversibly inhibited Ca(++)-activated
      contraction, more potently at lower Ca++ concentration and in phasic smooth
      muscle, but inhibited neither adenosine 5'-O-(tau-thiotriphosphate)-induced,
      Ca(++)-independent nor phorbol ester-induced contractions. These results indicate
      that azelastine is a genuine Ca++ antagonist that inhibits voltage-gated Ca++
      inward current and agonist-induced Ca++ release and Ca++ sensitization.

PMID- 1347569
TI  - Binding of typical and atypical antipsychotic agents to transiently expressed 5
      HT1C receptors.
AB  - We determined the affinities of clozapine and 21 other typical and atypical
      antipsychotic agents for the cloned 5-hydroxytryptamine-1C (5-HT1C) receptor. For
      these studies, 5-HT1C receptors were transiently expressed in COS-7 cells using
      the vector pSVK3-5HT1C. We discovered that clozapine and several other putative
      typical and atypical antipsychotic agents (loxapine greater than tiosperone
      greater than SCH23390 greater than fluperlapine greater than rilapine greater
      than chlorpromazine) had relatively high affinities (7-30 nM) for the cloned 5
      HT1C receptor. Other antipsychotic agents (risperidone greater than tenilapine
      greater than mesoridazine greater than thioridazine greater than cis
      fluphenthixol) had intermediate affinities (30-100 nM), whereas many other
      antipsychotics (fluphenazine greater than spiperone greater than amperozide
      greater than melperone greater than thiothixene greater than haloperidol,
      metoclopramide, pimozide, domperidone, sulpiride) had low affinities (greater
      than 500 nM) for the cloned 5-HT1C receptor. The results indicate that although
      several putative atypical antipsychotic agents have high affinities for the
      cloned rat 5-HT1C receptor, the spectrum of drug binding does not correlate with
      the atypical nature of these compounds.

PMID- 1347570
TI  - Somatostatin causes vasoconstriction, reduces blood flow and increases vascular
      permeability in the rat central nervous system.
AB  - Using radiolabeled microspheres, spinal cord blood flow was measured after spinal
      subarachnoid injections of 3.1- to 12.5-nmol doses of somatostatin through either
      indwelling i.t. catheters or acutely inserted intervertebral needles. With either
      injection technique, somatostatin caused significant dose-dependent reductions in
      thoracic and lumbosacral blood flow that could be partially blocked by a 5-min
      preinjection of the somatostatin receptor antagonist cyclo[7-aminoheptanoyl-Phe-D
      Trp-Lys-Thr(Bzl)], which has previously been shown to block the hindlimb
      flaccidity produced by these doses of somatostatin in conscious rats. The
      duration of these blood flow changes were appreciably less in the rats injected
      through indwelling i.t. catheters. Somatostatin-induced reductions in spinal cord
      perfusion were accompanied by transient pressor responses, reduced cardiac
      output, 3-fold increases in spinal cord cerebrospinal fluid lactic acid
      concentrations and breakdown of the blood-spinal cord barrier, as reflected by
      significantly increased extravasation of [125I]bovine serum albumin. By 24 hr
      postinjection, a 12.5-nmol dose of somatostatin caused appreciable spinal cord
      cellular injury, as evidenced by significant elevations in cerebrospinal fluid
      concentrations of lactate dehydrogenase. After topical application to exposed
      pial vessels of the parietal cortex, comparable doses of somatostatin caused
      immediate intense dose-related arteriolar vasospasm and subsequent extravasation
      of the visible macromolecular tracer Evans blue dye. We conclude that
      somatostatin has significant vasoconstrictory effects on the blood vessels of the
      brain and spinal cord of the rat that must be recognized and appreciated when
      studying its neuropharmacological actions in vivo.

PMID- 1347571
TI  - Nation calls for increased yew tree collection.

PMID- 1347572
TI  - Beta-blockers and depression. Evidence against an association.
AB  - OBJECTIVE: To evaluate the relationship between beta-blockers and depression.
      DESIGN: Case-control study. SETTING: New Jersey Medicaid recipients during July
      1980 to December 1983. PARTICIPANTS: New depression case patients (N = 4302) were
      identified from Medicaid claims for depression markers (antidepressant drugs, in
      hospital depression diagnosis, or electroconvulsive therapy). Control patients
      were randomly selected and matched on the basis of Medicaid enrollment on the
      case patients' date for first depression marker (index date), birth year, sex,
      race, and nursing home residency status. MAIN EXPOSURE MEASURE: beta-Blocker use
      as evidenced by prescription claims in the year before the index date. RESULTS:
      Case patients overall were more likely to have taken beta-blockers (simple,
      matched odds ratio [OR] of 1.45; 95% confidence interval [CI], 1.29 to 1.62).
      Controlling for confounders (benzodiazepine use, frequent outpatient visits, and
      frequent use of medications other than beta-blockers) resulted in a null effect
      (OR = 0.98; 95% CI, 0.87 to 1.12). The ORs were consistently lower for case
      patients with a depression diagnosis or electroconvulsive therapy than for cases
      with only antidepressant use as a marker. These results did not vary by age, sex,
      race, nursing home status, or use of other selected specific medications.
      CONCLUSIONS: Ongoing beta-blocker use was not causally related to markers of
      depression. The difference between this study and those it contradicts is that
      this one identified certain confounding variables that accounted for the apparent
      relationship.

PMID- 1347574
TI  - Beta-blockers and depression. The clinician's dilemma.

PMID- 1347573
TI  - Spectrum of disease in persons with human immunodeficiency virus infection in the
      United States.
AB  - OBJECTIVE: To describe the spectrum of disease in persons with human
      immunodeficiency virus (HIV) infection. DESIGN: Retrospective survey of medical
      records. SETTING: More than 50 clinics, hospitals, and private medical practices
      in nine US cities. PATIENTS: A total of 626 women and 7008 men 13 years of age or
      older with HIV infection who received medical care from January 1990 through
      March 1991 were consecutively enrolled. MAIN OUTCOME MEASURES: Any history of
      diseases in the 1987 case definition for the acquired immunodeficiency syndrome
      (AIDS), and during the 12-month period preceding enrollment (baseline period),
      the occurrence of other major diseases, hospitalizations, and results of CD4+
      lymphocyte counts. RESULTS: Thirty-two percent of persons met the 1987 case
      definition for AIDS. The occurrence of an AIDS-indicator disease during the
      baseline period ranged from 3% (33/1011) to 46% (1254/2748) among persons with
      CD4+ lymphocyte counts of 0.50 x 10(9)/L or greater and fewer than 0.20 x 10(9)/L
      (greater than or equal to 500 and less than 200 CD4+ lymphocytes per microliter),
      respectively, and, at comparable CD4+ lymphocyte levels, was similar among women
      compared with men, and among persons who reported intravenous drug use compared
      with men who reported male-to-male sex. The frequency of one or more other major
      infectious diseases (eg, other pneumonias, bacterial sepsis, pulmonary
      tuberculosis) ranged from 6% to 16% among persons with CD4+ lymphocyte counts of
      0.50 x 10(9)/L or greater and fewer than 0.20 x 10(9)/L, respectively; these
      illnesses were also associated with a history of intravenous drug use. Among
      persons who did not meet the 1987 AIDS case definition, 30% of those with an
      available CD4+ lymphocyte count had fewer CD4+ cells than 0.20 x 10(9)/L, 8% had
      one or more major infectious diseases, and 14% had one or more hospital
      admissions. CONCLUSIONS: For every person with AIDS at these sites, two
      additional persons with HIV infection were receiving medical care, many of whom
      had severe immunosuppression and a broad spectrum of serious HIV-related disease.

PMID- 1347575
TI  - [Vecuronium-induced neuromuscular blockade in two patients with
      hyperparathyroidism and a patient with hypoparathyroidism].
AB  - Vecuronium-induced neuromuscular blockade was evaluated in two patients with
      primary hyperparathyroidism and in a patient with hypoparathyroidism. A 39 year
      old male with typical primary hyperparathyroidism was scheduled for surgical
      removal of the parathyroid adenoma. Serum levels of calcium and ionized calcium
      were 15.0 mg.dl-1 and 1.95 mmol.l-1, respectively. A 44 year old female suffering
      from primary hyperparathyroidism was also scheduled for surgical removal of the
      adenoma. Serum levels of calcium and ionized calcium were 12.5 mg.dl-1 and 1.51
      mmol.l-1, respectively. A 63 year old male, suffering from postoperative
      secondary hypoparathyroidism and treated with calcium, was scheduled for surgical
      removal of the recurrent pharyngeal cancer. Serum levels of calcium and ionized
      calcium were 9.0 mg.dl-1 and 1.15 mmol.l-1, respectively. Anesthesia was induced
      with thiamylal 4-5 mg.kg-1 and vecuronium 0.08 mg.kg-1 and was maintained with
      70% nitrous oxide in oxygen and fentanyl in all three patients. Neuromuscular
      blockade following the administration of vecuronium was measured by a big toe
      abduction evoked by supramaximal stimulation of the tibial nerve (Myograph 2000,
      Biometer, Denmark). In order to evaluate the effect of serum calcium level on
      vecuronium neuromuscular blockade, ten patients with normal serum levels of
      calcium, were examined in the same fashion. In only one patient with
      hyperparathyroidism, whose serum calcium was 15.0 mg.dl-1, the onset and the
      duration of vecuronium were later and shorter than those of other patients with
      normal serum levels of calcium. In conclusion, we should pay attention to the
      antagonistic responses to vecuronium in patients with severely high levels of
      serum calcium.

PMID- 1347576
TI  - [A single bolus dose of vecuronium for rapid endotracheal intubation].
AB  - The changes in EMG evoked by train-of-four (TOF) stimulation of ulnar nerve were
      recorded to determine proper single bolus dose of vecuronium for endotracheal
      intubation in surgical patients. Onset and duration of neuromuscular block were
      judged by percent depression of EMG. Mean time intervals for 90% depression in
      TOF seen in 0.10 mg.kg-1 vecuronium group (n = 10), 0.15 mg.kg-1 vecuronium group
      (n = 10) and 0.20 mg.kg-1 vecuronium group (n = 10), were 181.1 sec, 135.0 sec
      and 120.0 sec, respectively. Similarly, mean time intervals for 100% depression
      for each vecuronium group were 240.0 sec, 177.5 sec and 160.0 sec, respectively.
      Onset time intervals in both 0.15 mg.kg-1 and 0.20 mg.kg-1 groups were
      significantly shorter than that in 0.10 mg.kg-1 group (P less than 0.05). On the
      other hand, mean time intervals for 25% recovery in EMG were 53.6 min in 0.10
      mg.kg-1 group, 63.3 min in 0.15 mg.kg-1 group and 104.3 min in 0.20 mg.kg-1
      group. No statistically significant difference was observed in recovery time
      between 0.10 mg.kg-1 and 0.15 mg.kg-1 group. These results indicate that the
      appropriate dose of vecuronium for rapid intubation is considered to be 0.15
      mg.kg-1. This dose is allowable for surgical procedures of short duration.

PMID- 1347577
TI  - [Adult T-cell leukemia with Ki-1 expression].
AB  - A 64-year-old man was admitted to our hospital complaining of fever and edema in
      February, 1990. Lymph node biopsy revealed diffuse lymphoma pleomorphic type
      according to the LSG classification. On hematological examination, leukocyte
      count was 23,500/microliters, of which 36% abnormal lymphocytes expressing CD2,
      CD3, CD4 and CD25 as same as the lymph node cells. Anti-HTLV-I antibody in serum
      was positive. From these data, the diagnosis of adult T-cell leukemia (ATL) was
      made. ATL cells in the blood and lymph node expressed CD30 (Ki-1). CD30 positive
      ATL cells derived from the blood was increased after short-term culture. The
      induction of Ki-1 antigen in cell lines and short-term cultured cells from ATL
      patients was accompanied by the appearance of the HTLV-I related antigen. Then,
      we suggest that there was some relation between expression of the Ki-1 antigen
      and activation by HTLV-I in ATL cells.

PMID- 1347578
TI  - Antiviral agents.
AB  - In recent years, the antiviral armamentarium has expanded considerably. Currently
      available agents are virustatic, inhibiting specific steps in the process of
      viral replication. No agent is active against nonreplicating or latent viruses.
      Acyclovir is useful in the treatment of genital herpes, herpes simplex
      encephalitis, mucocutaneous herpetic infection, varicella infection in the
      immunosuppressed host, and herpes zoster infection in the normal and the
      immunosuppressed host. It can also be used for prevention of herpesvirus
      infection in immunocompromised patients. Ganciclovir is indicated for the
      treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency
      syndrome (AIDS) and is effective in the management of organ-specific
      cytomegalovirus infection in other immunocompromised patients. Chronic hepatitis
      C and condyloma acuminatum due to human papillomavirus respond to therapy with
      interferon alfa-2b. Patients with human immunodeficiency virus infection and CD4
      lymphocyte counts of less than 500 cells/mm3 should be treated with zidovudine.
      Amantadine is useful in a therapeutic and prophylactic role in the management of
      influenza A virus infection. With the expanded use of and indications for
      antiviral therapy, clinically significant resistance to these agents has been
      encountered with increasing frequency.

PMID- 1347579
TI  - Antituberculous agents.
AB  - Antituberculous agents have radically improved the prognosis of patients with
      active tuberculosis. Generally, 6-month and 9-month antituberculous regimens have
      been successful, and surgical therapy is rarely needed. Extrapulmonary
      tuberculosis should be managed with the same drug regimens as pulmonary
      tuberculosis. The major cause of therapeutic failure is poor compliance of the
      patient in taking the prescribed medication regularly. A second cause of failure
      of treatment is resistance of tubercule bacilli to antimicrobial agents used.
      When failure of treatment is apparent, careful reassessment by physicians
      experienced in the treatment of tuberculosis is indicated. A single drug should
      never be added to a failing regimen. Isoniazid administered prophylactically for
      6 to 12 months is effective in most cases.

PMID- 1347580
TI  - [Consider diagnosis of nephropathia epidemica even in southern Sweden!].

PMID- 1347581
TI  - Fibrinogen genotype and risk of peripheral atherosclerosis.
AB  - There is conflicting evidence about the influence of fibrinogen genotype on
      plasma fibrinogen concentrations, and the relation between genotype and
      atherosclerotic disease has not been studied. In a population-based case-control
      study we aimed to find out whether certain fibrinogen genotypes are associated
      with an increased risk of peripheral atherosclerosis. 121 subjects with
      peripheral arterial disease and 126 healthy controls matched for age and sex were
      selected from a random population sample aged 55-74 years in the Edinburgh Artery
      Study. Mean fibrinogen concentrations were higher in cases than in controls (3.12
      [95% confidence interval 2.99-3.26] vs 2.75 [2.64-2.85], p less than 0.001). A
      greater proportion of cases than controls were homozygous or heterozygous for an
      allele at the beta fibrinogen locus (4.2 kb allele, Bcl I digestion); the allele
      frequency was 0.197 in cases and 0.097 in controls (p less than 0.005). Extended
      haplotypes for 4.2 kb heterozygotes were also associated with an increased risk
      of peripheral arterial disease. However, haplotype had only a small effect on the
      association of plasma fibrinogen concentration with disease, and the relation of
      haplotype with disease was independent of age, sex, social class, smoking status,
      plasma fibrinogen, alcohol consumption, body mass index, and diabetes mellitus.
      We conclude that variation at the beta fibrinogen locus is associated with an
      increased risk of peripheral atherosclerosis. The influence is not mediated
      simply by way of increased fibrinogen concentrations but could be due to a
      structurally variant fibrinogen or linkage disequilibrium with a neighbouring
      gene.

PMID- 1347582
TI  - Voluntary dehydration and heat intolerance in cystic fibrosis.
AB  - Although exercise may be beneficial in cystic fibrosis (CF), patients' low
      tolerance to climatic heat stress means that physical exertion can increase
      morbidity and mortality. We postulated that the high salt content of CF patients'
      sweat and the consequent absence of body-fluid hyperosmolality during a long
      episode of sweating might deprive such patients of a thirst stimulus. Eight
      children with CF (four boys, four girls; aged 9.5-14.1 years) and eight controls,
      matched for age and sex, attended two randomly ordered sessions of exercise
      (cycling) in a chamber at 31-33 degrees C, relative humidity 43-47%. 20 min bouts
      of exercise (at 45% of predetermined maximum oxygen uptake) were interspersed
      with 25 min rest periods. At one session, chilled water was given every 15-20 min
      to replace fluid lost; at the other, drinking was guided by the child's thirst.
      At the thirst-guided session, CF patients drank much less than the controls did
      (0.80% vs 1.73% initial body weight) and lost twice as much fluid (1.57% vs 0.78%
      initial body weight). The recovery of heart rate after exercise was slower in CF
      patients, but there were no other signs of heat strain. The groups did not differ
      in any variable during the forced drinking session. We conclude that children
      with CF underestimate their fluid needs and undergo excessive dehydration during
      extended exposure to hot conditions.

PMID- 1347583
TI  - Pulmonary toxic effects of continuous desferrioxamine administration in acute
      iron poisoning.
AB  - The drug of choice for the treatment of iron poisoning is desferrioxamine, though
      the best route of administration, dose, and duration of treatment are unclear. We
      report fatal lung injury in four patients who were treated with continuous
      intravenous infusions. The patients, aged 19-26 years, had received
      desferrioxamine infusions of 15 mg/kg per h for 65-92 h. Respiratory distress
      developed after 32-72 h. The patients met clinical, physiological, and necropsy
      criteria for the diagnosis of adult respiratory distress syndrome (ARDS); none
      had any of the known risk factors for the development of this disorder. We
      reviewed the records of forty-three iron-poisoned patients treated with
      desferrioxamine infusions. No patient treated for less than 24 h had pulmonary
      complications; however, of the fourteen treated for longer than 24 h, four were
      the patients with ARDS and four others had pulmonary oedema of other causes. We
      suggest that the pulmonary complications are caused by continuous infusion of
      desferrioxamine and that the ARDS in these patient was a consequence of free
      radical generation. We recommend that desferrioxamine infusion should not be
      administered for longer than 24 h.

PMID- 1347584
TI  - Relation between coronary risk and coronary mortality in women of the Renfrew and
      Paisley survey: comparison with men.
AB  - Most epidemiological and intervention studies in patients with coronary artery
      disease have focused on men, the assumption being that such data can be
      extrapolated to women. However, there is little evidence to support this belief.
      We have completed a fifteen-year follow-up of 15,399 adults, including 8262
      women, who lived in Renfrew and Paisley and were aged 45-64 years when screened
      between 1972 and 1976. We identified 490 deaths from coronary heart disease (CHD)
      in women and 878 in men. Women were more likely to have high cholesterol, to be
      obese, and to come from lower social classes than men, but they smoked less and
      had similar blood pressures. The relative risk--top to bottom quintile (95% Cl)-
      of cholesterol for coronary death after adjustment for all other risk markers was
      slightly greater in women (1.77 [1.45,2.16]) than in men (1.56 [1.32, 1.85]), but
      absolute and attributable risk were lower. Thus, women in the top quintile for
      cholesterol had lower coronary mortality (6.1 deaths per thousand patient years)
      than men in the bottom quintile (6.8 deaths per thousand patient years).
      Moreover, it was estimated that there would have been only 103 (21%) fewer CHD
      deaths in women, yet 211 (24%) fewer in men, if mortality had been the same for
      women and men in the lowest quintiles of cholesterol. Trends showing similar
      relative risks in these women, but lower absolute and attributable risks than in
      men, were present for smoking, diastolic blood pressure, and social class. There
      was no relation between obesity and coronary death after adjustment for other
      risks. Our results suggest that some other factors protect women against CHD. The
      potential for women to reduce their risk of CHD by changes in lifestyle may be
      less than for men.

PMID- 1347585
TI  - Glomerulonephritis with end-stage liver disease in childhood.
AB  - Renal biopsies were done perioperatively in 18 children receiving liver grafts.
      All specimens showed glomerulonephritis, which was mesangial-proliferative in 15
      and mesangio-capillary in 3. Of the 16 children who were alive four or more
      months after transplantation, only 1 showed progressive deterioration of renal
      function; 1 other had a subnormal but static glomerular filtration rate. In all 6
      children who had proteinuria before operation, the urine became normal.

PMID- 1347586
TI  - Transoesophageal echocardiography.

PMID- 1347587
TI  - Adhesions and anodynes.

PMID- 1347588
TI  - Chlamydial infections: therapeutic options.

PMID- 1347589
TI  - Is aluminium a dementing ion?

PMID- 1347590
TI  - Gene therapy for cancer.
AB  - The molecular basis of cancer is now understood to involve activation of dominant
      oncogenes and inactivation of tumour suppressor genes, and these genetic events
      may represent novel targets for cancer therapy. This review focuses on the
      potential use and ethical implications of gene transfer to alter the behaviour of
      somatic cells in cancer patients. Antisense nucleic acids and ribozymes represent
      informational drugs that may be used to modulate the expression of selected genes
      and suppress malignant behaviour in cancer cells. Genetic immunomodulation by
      introducing genes for cytokines into cancer cells or lymphocytes can stimulate a
      cytotoxic immune response against the tumour. Gene transfer techniques can be
      applied to target prodrug activation specifically to tumour cells and also to
      protect normal tissues against toxic chemotherapy. Gene replacement therapy could
      even be used to restore the function of defective tumour suppressor genes.

PMID- 1347591
TI  - Complications of acute stroke.

PMID- 1347592
TI  - Secondary prevention of stroke.

PMID- 1347593
TI  - Low serum cholesterol and suicide.
AB  - Primary prevention trials which have shown that the lowering of serum cholesterol
      concentrations in middle-aged subjects by diet, drugs, or both leads to a
      decrease in coronary heart disease have also reported an increase in deaths due
      to suicide or violence. There has been no adequate explanation for this
      association. I have reviewed the relevant published work and describe a
      physiological mechanism that might account for this curious finding. One of the
      functions of serotonin in the central nervous system is the suppression of
      harmful behavioural impulses. When mouse brain synaptosomal membrane cholesterol
      is increased there is a pronounced increase in the number of serotonin receptors.
      Low membrane cholesterol decreases the number of serotonin receptors. Since
      membrane cholesterol exchanges freely with cholesterol in the surrounding medium,
      a lowered serum cholesterol concentration may contribute to a decrease in brain
      serotonin, with poorer suppression of aggressive behaviour.

PMID- 1347594
TI  - Missed diagnosis of testicular cancer.

PMID- 1347595
TI  - IVIG guidelines.

PMID- 1347596
TI  - Antibiotic prophylaxis and endocarditis.

PMID- 1347597
TI  - Antibiotic prophylaxis and endocarditis.

PMID- 1347598
TI  - Platelet size changes after myocardial infarction.

PMID- 1347599
TI  - Paf-acether in stool as marker of intestinal inflammation.

PMID- 1347600
TI  - Sex of children born to women with cystic fibrosis.

PMID- 1347601
TI  - Ciprofloxacin and typhoid fever.

PMID- 1347602
TI  - Ciprofloxacin and typhoid fever.

PMID- 1347603
TI  - Genetic relation between Vibrio cholerae O1 strains in Ecuador and Bangladesh.

PMID- 1347604
TI  - Influenza vaccination in asthma.

PMID- 1347605
TI  - Epoprostenol infusions in thrombotic microangiopathy of pregnancy.

PMID- 1347606
TI  - Capture-recapture methods.

PMID- 1347607
TI  - Methimazole in animal feed and congenital aplasia cutis.

PMID- 1347608
TI  - Homozygous protein C deficiency with late onset and recurrent coumarin-induced
      skin necrosis.

PMID- 1347609
TI  - Prevention of shoulder pain after laparoscopy.

PMID- 1347610
TI  - Breastfeeding and intelligence.

PMID- 1347611
TI  - Reflux nephropathy.

PMID- 1347612
TI  - Reflux nephropathy.

PMID- 1347613
TI  - Helicobacter pylori gastritis and gastric MALT-lymphoma.

PMID- 1347614
TI  - Proteolysis of human IgG by house dust mite allergens.

PMID- 1347615
TI  - Calcitonin in painful diabetic neuropathy.

PMID- 1347616
TI  - Drug interactions in use of dapsone for Pneumocystis carinii prophylaxis.

PMID- 1347617
TI  - Uteroplacental flow velocity waveforms after CVS.

PMID- 1347618
TI  - Seasonal variation in presentation of Pneumocystis carinii pneumonia.

PMID- 1347619
TI  - Tuberculosis in perspective.

PMID- 1347620
TI  - Cot deaths and sleep position campaigns.

PMID- 1347621
TI  - Studying X inactivation.

PMID- 1347622
TI  - Illness behaviour after common whiplash.

PMID- 1347623
TI  - Stroke.

PMID- 1347624
TI  - Stroke.

PMID- 1347625
TI  - Stroke.

PMID- 1347626
TI  - Measles virus antibody in aqueous humour of patients with uveitis associated with
      multiple sclerosis.

PMID- 1347627
TI  - NO inhibitors and septic shock.

PMID- 1347628
TI  - Levodopa challenge test in Parkinson's disease.

PMID- 1347629
TI  - Gardener's mydriasis.

PMID- 1347630
TI  - Transient selective C4 deficiency of infancy.

PMID- 1347631
TI  - Cyclic AMP accumulation alters calmodulin localization in SK-N-SH human
      neuroblastoma cells.
AB  - In SK-N-SH human neuroblastoma cells, the muscarinic agonist carbachol promotes
      polyphosphoinositide (PPI) hydrolysis via M3 receptors and increases cyclic AMP
      levels through an unidentified mechanism. Activation of PPI hydrolysis by
      carbachol elicits a robust translocation of CaM from membranes into cytosol which
      was previously shown to be mimicked by the addition of the calcium ionophore
      ionomycin and the phorbol ester TPA28. The effect of agonist-stimulated second
      messenger production on CaM localization was determined by activating receptors
      that increase and decrease adenylyl cyclase activity on SK-N-SH cells. VIP (10
      microM), prostaglandin E1 (30 microM) and forskolin (10 microM) all increased
      adenylyl cyclase activity 8- to 10-fold above the activity with 1 microM GTP.
      Carbachol (100 microM) did not stimulate adenylyl cyclase activity. The alpha 2
      adrenergic agonist UK 14,304 (0.1 microM) and the delta and mu opioid DPDPE (10
      microM) and DAMGO (10 microM) inhibited forskolin-stimulated cyclic AMP formation
      by 27-32%. CaM did not stimulate adenylyl cyclase activity. Incubation of cells
      with vasoactive intestinal polypeptide (VIP), dibutyryl cyclic AMP and forskolin,
      resulted in 30% decrease in membrane CaM and an increase in cytosolic CaM of 40
      50%. The CaM translocation with the combination of an agent that elevates cyclic
      AMP levels and a low dose of carbachol was not different from that observed with
      either agent alone. UK 14,304, DPDPE and DAMGO potentiated carbachol-stimulated
      increases in cytosolic CaM. Upon the addition of carbachol, a 5-fold increase in
      intracellular calcium concentration measured with fura-2 fluorescence was
      observed. VIP and UK 14,304 elevated intracellular calcium concentrations 2 to 3
      fold, while forskolin (10 microM) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347633
TI  - The effects of excitatory amino acids on proenkephalin and prodynorphin mRNA
      levels in the hippocampal dentate gyrus of the rat; an in situ hybridization
      study.
AB  - Injection of N-methyl-D-aspartate (NMDA, 7.5 micrograms) kainate (1 microgram) or
      quisqualate (2 micrograms) into the rat dorsal hippocampus induced wet-dog shakes
      and convulsions. As shown by an in situ immunohistochemical analysis, 3 h after
      the excitatory amino acids injections the rats displayed a bilateral profound
      elevation of the proenkephalin and prodynorphin mRNA levels in dentate gyrus
      granule cells (2-3 or 1.5-2 fold higher than control levels, respectively).
      Pretreatment of rats with D-amino-phosphonovalerate (D-APV, 10 micrograms), a
      selective antagonist of NMDA receptor, prevented the behavioral and biochemical
      changes evoked by NMDA. The changes in the behavior and gene expression evoked by
      kainate or quisqualate were diminished in rats which received 6-cyano-7
      nitroquinoxaline-2,3-dion (CNQX, 2 micrograms), a putative antagonist of
      quisqualate and kainate receptors. The study demonstrated that activation of
      NMDA, quisqualate or kainate receptors in the hippocampus induced seizures
      associated with a marked increase in the proenkephalin (PENK) and the
      prodynorphin (PDYN) gene expression in the rat dentate gyrus.

PMID- 1347632
TI  - Differential induction of immediate early genes by excitatory amino acid receptor
      types in primary cultures of cortical and striatal neurons.
AB  - In primary cultures of neurons from cerebral cortex and striatum, 30 s
      stimulation with the excitatory amino acid glutamate elicited a 5 to 9-fold
      increase in immediate early gene (IEG) mRNAs. Glutamate increased c-fos, c-jun,
      jun-B, and NGFI-A (zif/268) mRNAs by binding to both alpha-amino-3-hydroxy-5
      methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor
      types, and increased c-fos, jun-B, and NGFI-A mRNAs by binding to the
      metabotropic receptor. NMDA receptor activation elicited IEG expression by a
      transmembrane calcium influx; AMPA receptor-induced depolarization played a
      permissive role for the opening of the NMDA receptor channel. The protein kinase
      C (PKC) inhibitor H-7 (but not inhibitors of cyclic nucleotide-dependent and
      calcium/calmodulin-dependent protein kinases) partially blocked IEG expression
      induced by glutamate.

PMID- 1347634
TI  - Cellular localization of tyrosine hydroxylase mRNA and cholecystokinin mRNA
      containing cells in the ventral mesencephalon of the common marmoset: effects of
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
AB  - In situ hybridization histochemistry was used to localize tyrosine hydroxylase
      (TH) mRNA and cholecystokinin (CCK) mRNA-expressing cells in the ventral
      mesencephalon of the common marmoset (Callithrix jacchus) and to examine the
      effects of the dopaminergic (DA) neurotoxin, 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) on these two populations of neurons in the pars
      compacta of the substantia nigra (SNc) and ventral tegmental area (VTA). X-ray
      film and liquid emulsion autoradiography of brain sections hybridized with an 35S
      labelled synthetic 45-mer antisense human TH oligonucleotide probe showed strong
      hybridization signals and dense populations of TH mRNA expressing cells in the
      SNc and VTA at all levels, in the control marmoset brain. In the MPTP-treated
      brain, there was a substantial reduction of TH mRNA in the ventral midbrain. The
      loss of TH mRNA-expressing cells amounted to 98% in the lateral SNc, 88% in the
      medial SNc and 33% in the VTA. In situ hybridization of adjacent sections with an
      35S-labelled synthetic 45-mer antisense human CCK oligonucleotide probe showed a
      weak hybridization signal for CCK mRNA in the ventral midbrain of the control
      brain. Emulsion autoradiography demonstrated CCK mRNA expressing cells in the SNc
      and VTA at all levels with the number of cells in the VTA similar to that for TH
      mRNA. However, the number of cells in the SNc expressing CCK mRNA was a fraction
      (1/4) of that expressing TH mRNA; moreover, the level of expression per cell was
      substantially less than that for TH mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347636
TI  - Isolation, characterization, and genetic analysis of monosomic, aneuploid mutants
      of Candida albicans.
AB  - A white, prototrophic Candida albicans strain, heterozygous for the ADE2 gene
      (ade2/ADE2), was treated with the antimitotic agent methyl benzimidazole
      carbamate, and yielded red, adenine-requiring colonies at a rate of 4 x 10(-3),
      an order of magnitude higher than the spontaneous rate of Ade- colony formation.
      These red Ade- colonies were small, growing at approximately half the rate of the
      parent strain, and gave rise to large red colonies spontaneously. When the
      chromosomes of the small red colonies were separated by pulsed-field gel
      electrophoresis, the band hybridizing with the ADE2 gene was diminished in
      staining intensity by half relative to the parent and large red-colony strains.
      Restriction fragment-length polymorphism analysis and auxotrophic mutant spectra
      after mutagenesis suggested that the small red Ade- strains were monosomic
      aneuploids lacking one of a pair of chromosome homologues, while the large red
      strains had regained a homologue, presumably via a second non-disjunction event.
      Parasexual genetic analysis of two of the auxotrophs isolated from a putative
      aneuploid suggested that both mutations were linked to the ADE2 gene. These
      experiments suggest that targeted chromosome loss and monosomic, aneuploid
      strains have the potential to extend the scope of genetic analysis in this
      diploid, asexual organism.

PMID- 1347635
TI  - Immune-mediated cytopenia following bone marrow transplantation. Case reports and
      review of the literature.
AB  - We describe 3 cases of immune-mediated cytopenia occurring after bone marrow
      transplantation (BMT). In 1 case, only the platelet line was affected, whereas in
      the other 2 cases more than 1 cell lineage was involved simultaneously. Two of
      the cases presented with falling peripheral blood counts following apparently
      normal early engraftment, while in 1 of the cases the affected lineage failed to
      appear in the peripheral blood despite normal engraftment of the other lineages.
      In all 3 cases the cytopenia improved following the initiation of treatment with
      systemic corticosteroids. Immune-mediated cytopenia following bone marrow
      transplantation may occur via alloimmune or autoimmune mechanisms. Alloimmune
      cytopenias have arisen in the context of major or minor mismatches in the ABO
      system, but cases related to mismatches in the Rh system and other erythroid and
      non-erythroid alloantigen systems may also occur. Alloimmune cytopenias have been
      reported primarily in the setting of allogeneic BMT, whereas autoimmune
      cytopenias have been reported following both allogeneic and autologous BMT.
      Immune-mediated cytopenia may present as early as the day of transplant, or as
      late as many months afterward. The possibility of immune-mediated cytopenia
      should always be considered when unexpected peripheral blood cytopenia is
      present, or when unexpected hemolysis develops, following bone marrow
      transplantation. The diagnosis is supported by a normal appearance of the
      affected lineage or lineages in the bone marrow, the absence of other apparent
      causes for the cytopenia, and the presence of the relevant auto- or allo
      antibodies in the serum. However, any of these features may be absent in
      individual cases. The importance of these syndromes lies in the fact that they
      may be life-threatening, yet they often respond well to steroids or other
      standard immunosuppressive measures. It is important to be aware that effective
      prophylactic measures are available for patients receiving ABO- or Rh
      incompatible marrow.

PMID- 1347637
TI  - Silent pilin genes of Neisseria gonorrhoeae MS11 and the occurrence of related
      hypervariant sequences among other gonococcal isolates.
AB  - Pilin variation in Neisseria gonorrhoeae depends on a family of variant genes
      that undergo homologous, intragenic recombination. This work focuses on the
      repertoire of silent variant pilin genes in strain MS11, which contribute to the
      extensive variation of the expressed gene copy. A total of 17 silent copies were
      identified, which are, to varying degrees, truncated at their 5' coding region
      and grouped in seven distinct pil loci. Most silent copies belong to loci pilS1,
      pilS2 and pilS6, which contain six, two and three silent copies, respectively,
      tandemly arranged. The pilS5 and pilS7 loci each contain only a single copy. In
      addition, two silent copies are associated with each of the two pilE loci. By
      comparison with sequences present in the expressed gene of other variants of the
      same strain, it is suggested that each silent locus is capable of donating
      variant sequences into the expression locus and, thus, each silent copy can
      contribute to the variability of pilin expression. Often, concomitant with
      changes in the expressed copy, the silent copies of the pilE1 locus undergo
      recombinations as well. Analyses of unrelated clinical isolates of N. gonorrhoeae
      reveal homologies of hypervariant pilin sequences with those present in strain
      MS11, suggesting a limited diversity of such sequences within the gonococcal
      population and the existence of substantial functional constraints on the
      variability of pilin and pili. The data further indicate that hypervariant pilin
      sequences are subject to horizontal exchange and interstrain recombination.

PMID- 1347638
TI  - Linking prescription and patient-identifying data: a pilot study.
AB  - OBJECTIVE: To link a Pharmaceutical Benefits Scheme (PBS) prescription data set
      with patient-identifying data held by the Health Insurance Commission (HIC) and
      to then determine the prevalence of prescribing of cardiovascular drugs, non
      steroidal anti-inflammatory drugs, hypnotics and minor tranquillizers, and
      diuretics (prescribed without other cardiovascular drugs) by age and sex in two
      defined populations. DESIGN: Prescription data for a three-month period in 1985
      were matched with patient-identifying information to obtain a database which
      included the patient's age, sex and an identifying number, for each prescription
      record. The percentages of the population taking a drug from each of the drug
      categories mentioned above were then determined and the effect of age, sex and
      region of residence on prescribing prevalence was investigated using logistic
      regression analysis. SETTING: Two rural regions of Australia with a total
      population of 65,087 residents. MEASUREMENTS AND MAIN RESULTS: Of the 101,383
      prescriptions dispensed over the period 96% could be matched with HIC
      information. In the two regions combined, the percentages of the population
      taking a cardiovascular drug, non-steroidal anti-inflammatory drug, hypnotic or
      minor tranquilizer, or diuretic (without other cardiovascular drugs) were 10.4%,
      5.8%, 3.5% and 2.5%, respectively. Prescribing rates were higher for females than
      males, increased with age and varied between the two regions. Approximately 5% of
      women aged 30-39 years were taking diuretics without other cardiovascular drugs,
      compared with only 0.2% of men in the same age group. CONCLUSIONS: This pilot
      study illustrates the use of a patient-identified prescription database for drug
      utilisation review, therapeutic audit and hypothesis generation.

PMID- 1347639
TI  - Gi alpha 1 selectively couples somatostatin receptors to adenylyl cyclase in
      pituitary-derived AtT-20 cells.
AB  - Somatostatin (SRIF) receptors are coupled to the catalytic subunit of adenylyl
      cyclase via pertussis toxin-sensitive guanine nucleotide-binding regulatory
      proteins (G proteins). To identify which G proteins link SRIF receptors to
      adenylyl cyclase, G(o) alpha, Gi alpha, and its different subtypes were
      individually blocked in AtT-20 cell membranes with G alpha subtype-selective
      antisera. Antiserum directed against the carboxyl-terminal region of Gi alpha
      blocked SRIF inhibition of forskolin-stimulated adenylyl cyclase activity, and
      this effect was prevented by the peptide to which the antiserum was generated.
      However, antiserum directed against the carboxyl-terminal region of G(o) alpha
      did not affect SRIF inhibition of adenylyl cyclase activity, indicating that Gi
      alpha couples SRIF receptors to adenylyl cyclase but G(o) alpha does not. Peptide
      directed antisera against Gi alpha 1 completely blocked SRIF inhibition of
      adenylyl cyclase activity. In contrast, antisera directed against either Gi alpha
      2 or Gi alpha 3 did not affect the actions of SRIF. The results of these studies
      indicate that Gi alpha 1 selectively couples SRIF receptors to the catalytic
      subunit of adenylyl cyclase in AtT-20 cell membranes. Because previous studies
      have shown that SRIF receptors are able to couple to Gi alpha 1, Gi alpha 3, and
      G(o) alpha, the results suggest that different G proteins may specify the
      coupling of SRIF receptors to distinct cellular effector systems.

PMID- 1347640
TI  - Vasoactive intestinal polypeptide facilitates tyrosine hydroxylase induction by
      cholinergic agonists in bovine adrenal chromaffin cells.
AB  - The possibility that vasoactive intestinal polypeptide (VIP) may facilitate the
      nicotine-mediated induction of adrenal medullary tyrosine hydroxylase (TH) was
      investigated with primary cultures (5-7 days in vitro) of bovine adrenal
      chromaffin (BAC) cells. Exposure of BAC cells to 100 microM nicotine led to only
      a marginal increase in the amount of TH mRNA, TH protein, and TH activity. VIP,
      alone or in the presence of a phosphodiesterase inhibitor, produced a marked
      increase in TH mRNA, TH protein, and TH activity. Moreover, VIP together with
      nicotine, at concentrations that alone were devoid of effect, increased the
      amount of TH mRNA and TH activity. A synergistic effect of VIP and nicotine on
      cAMP accumulation in BAC cells was also apparent. The marginal effects of large
      doses of nicotine on both cAMP accumulation and TH induction were blocked
      completely by hexamethonium but were also partially inhibited by the VIP
      antagonist [p-chloro-D-Phe6,Leu17]-VIP. Nicotine may, therefore, stimulate the
      release of VIP from cultured BAC cells and VIP, in turn, by increasing cAMP, may
      synergize with nicotine to enhance TH gene expression.

PMID- 1347641
TI  - Distinct regulation of beta 1- and beta 2-adrenergic receptors in Chinese hamster
      fibroblasts.
AB  - The agonist-induced reduction of beta-adrenergic receptor (beta AR) cell surface
      density is a well documented phenomenon. The mechanisms responsible for this
      regulation have been well characterized for the beta 2AR. They include a rapid
      sequestration of the receptor away from the cell surface in a vesicular
      compartment and a longer term down-regulation of the total beta 2AR number. In
      contrast, very little is known about the cell surface regulation of the beta 1AR.
      In the present study, we have compared the agonist-mediated regulation of beta 1-
      and beta 2AR in Chinese hamster fibroblasts transfected with the cDNA encoding
      either beta AR subtype. Cells expressing similar numbers of the two beta AR
      subtypes were selected for the study. The expressed receptors exhibit typical
      beta 1- and beta 2AR selectivity for agonists and antagonists, as assessed by
      radioligand binding. Both receptors were found to be positively coupled to the
      adenylyl cyclase stimulatory pathway, but marked differences in the receptor
      regulation profiles were observed. Treatment of the cells expressing the beta 2AR
      with the agonist isoproterenol leads to a rapid sequestration of greater than 30%
      of the receptors away from the cell surface into a light vesicular fraction,
      where they are inaccessible to the hydrophilic ligand CGP-12177. In contrast,
      virtually no agonist-induced sequestration is observed in the cells expressing
      the beta 1AR. Longer exposure of the cells to isoproterenol leads to a time
      dependent reduction in the total number of beta ARs in both beta 1- and beta 2AR
      expressing cell lines. However, this down-regulation is significantly slower in
      the cells expressing the beta 1AR. In fact, no appreciable down-regulation of the
      beta 1ARs is detected in the first 4 hr of agonist treatment, compared with a
      down-regulation of greater than 50% of the beta 2ARs for the same period. After a
      24-hr treatment with isoproterenol, less than 20% of the original number of beta
      2ARs remain, whereas 60% of the beta 1ARs are still present after the same
      treatment. These results, therefore, suggest that, when expressed in an identical
      cell line, beta 1AR and beta 2AR follow distinct patterns of regulation. In fact,
      both agonist-induced sequestration and down-regulation are considerably blunted
      for the beta 1AR, compared with the beta 2AR.

PMID- 1347642
TI  - Cyclic AMP response element-binding protein and the catalytic subunit of protein
      kinase A are present in F9 embryonal carcinoma cells but are unable to activate
      the somatostatin promoter.
AB  - The cyclic AMP (cAMP) response elements (CREs) of the somatostatin and vasoactive
      intestinal peptide (VIP) promoters contain binding sites for CRE-binding protein
      (CREB) that are essential for cAMP-regulated transcription. Using F9 embryonal
      carcinoma cells, we show that the somatostatin and VIP promoters exhibit a
      differentiation-dependent cAMP response, demonstrating that these promoters are
      regulated by transcription factors that become active during differentiation.
      Lack of cAMP responsiveness of the somatostatin promoter in undifferentiated
      cells is not due to the absence of known positive-acting factors (the catalytic
      subunit of protein kinase A [cPKA] and CREB) or a general inhibition of protein
      kinase A activity. Since overexpression of exogenous cPKA and CREB is sufficient
      to activate the somatostatin promoter in undifferentiated cells, these findings
      suggest that a negative factor(s) represses endogenous cPKA and CREB. In contrast
      to their effects on somatostatin, exogenous CREB and cPKA do not activate the VIP
      promoter. Thus, despite coregulation during differentiation and the ability to
      bind CREB, the somatostatin and VIP promoters are not coordinately activated by
      CREB in undifferentiated F9 cells.

PMID- 1347644
TI  - Restriction site generating-polymerase chain reaction (RG-PCR) for the probeless
      detection of hidden genetic variation: application to the study of some common
      cystic fibrosis mutations.
AB  - In this report we describe the use of a DNA amplification technique in which
      modified primers introduce a base substitution adjacent to the codon of interest
      and create an artificial restriction site for the detection of mutations which do
      not produce or modify a naturally occurring restriction site (restriction site
      generating-polymerase chain reaction, RG-PCR). RG-PCR was developed and applied
      to the screening in an Italian population sample of several relatively common
      cystic fibrosis mutations which are not amenable to analysis with a known
      restriction endonuclease: G542X, 2869insG, Y913C, N1303K, and 1717-1GA. This
      method, which allows the identification of virtually any single base change by
      restriction enzyme analysis and without the need for molecular probes, is rapid
      and easy to perform. The combined use of RG-PCR for several different CF
      mutations in multiplex tests further expands the advantages of this approach.

PMID- 1347645
TI  - [Asthma: theory and practice in the year 1992].

PMID- 1347643
TI  - Progression of colorectal cancer is associated with multiple tumor suppressor
      gene defects but inhibition of tumorigenicity is accomplished by correction of
      any single defect via chromosome transfer.
AB  - Carcinogenesis is a multistage process that has been characterized both by the
      activation of cellular oncogenes and by the loss of function of tumor suppressor
      genes. Colorectal cancer has been associated with the activation of ras oncogenes
      and with the deletion of multiple chromosomal regions including chromosomes 5q,
      17p, and 18q. Such chromosome loss is often suggestive of the deletion or loss of
      function of tumor suppressor genes. The candidate tumor suppressor genes from
      these regions are, respectively, MCC and/or APC, p53, and DCC. In order to
      further our understanding of the molecular and genetic mechanisms involved in
      tumor progression and, thereby, of normal cell growth, it is important to
      determine whether defects in one or more of these loci contribute functionally in
      the progression to malignancy in colorectal cancer and whether correction of any
      of these defects restores normal growth control in vitro and in vivo. To address
      this question, we have utilized the technique of microcell-mediated chromosome
      transfer to introduce normal human chromosomes 5, 17, and 18 individually into
      recipient colorectal cancer cells. Additionally, chromosome 15 was introduced
      into SW480 cells as an irrelevant control chromosome. While the introduction of
      chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable
      clones, cell lines were established after the introduction of chromosomes 15, 5,
      and 18. Hybrids containing chromosome 18 are morphologically similar to the
      parental line, whereas those containing chromosome 5 are morphologically distinct
      from the parental cell line, being small, polygonal, and tightly packed. SW480
      chromosome 5 hybrids are strongly suppressed for tumorigenicity, while SW480
      chromosome 18 hybrids produce slowly growing tumors in some of the animals
      injected. Hybrids containing the introduced chromosome 18 but was significantly
      reduced in several of the tumor reconstitute cell lines. Introduction of
      chromosome 5 had little to no effect on responsiveness, whereas transfer ot
      chromosome 18 restored responsiveness to some degree. Our findings indicate that
      while multiple defects in tumor suppressor genes seem to be required for
      progression to the malignant state in colorectal cancer, correction of only a
      single defect can have significant effects in vivo and/or in vitro.

PMID- 1347647
TI  - [beta-adrenergic agonists and mortality and morbidity in asthma].

PMID- 1347646
TI  - [Preventive therapy essential in the treatment of patients with COPD].

PMID- 1347649
TI  - Metabolic compartmentation of glutamate and glutamine: morphological evidence
      obtained by quantitative immunocytochemistry in rat cerebellum.
AB  - An electron microscopic, double-labelling immunocytochemical procedure was used
      to assess the level of fixed glutamate and glutamine in different cell profiles
      in ultrathin sections of rat cerebellar cortex. The procedure was based on
      sequential immunolabelling with two rabbit antisera, using gold particles of
      different sizes as markers and formaldehyde vapour as a means to avoid
      interference between the two incubations. Model sections containing a series of
      known concentrations of the respective amino acids (aldehyde--fixed to rat brain
      protein) were incubated together with the tissue material. These revealed a close
      to linear relationship between gold particle density and antigen concentration
      throughout the range of biological relevance. The ratio between the density of
      the two categories of gold particles was calculated for the individual profile
      types. This ratio showed a 20-fold variation, with the highest
      glutamate/glutamine ratios obtained for putative excitatory terminals (terminals
      of parallel fibres in the outer part of the molecular layer, followed by mossy
      and climbing fibre boutons) and the lowest for glial cells (Bergmann glia,
      astrocytes in the granule cell layer, and oligodendrocytes). Granule cell bodies
      and dendrites, and cell bodies and processes of putative GABAergic cells
      (Purkinje, basket and Golgi cells) displayed intermediate ratios. The ratios
      corresponded to millimolar ratios (mM fixed glutamate/mM fixed glutamine) ranging
      from 4.5 to 0.2, tentatively assessed by adjusting for differences in labelling
      efficiency of the two antigens. Our results show that the compartmentation of
      glutamate and glutamine, an issue previously addressed mainly in the test tube,
      can be studied in morphologically intact preparations at a resolution that
      matches the complexity of CNS tissue. The data indicate that glutamate is
      effectively converted to glutamine in all categories of glial cells, and that
      glutamate synthesis prevails in each of the three types of excitatory terminals
      in the cerebellar cortex. Terminals of putative GABAergic cells form a distinct
      low glutamate/low glutamine compartment.

PMID- 1347648
TI  - In vivo modulation of N-methyl-D-aspartate receptor-dependent long-term
      potentiation by the glycine modulatory site.
AB  - The role of the glycine modulatory site in N-methyl-D-aspartate receptor function
      was examined by determining the effect of the glycine site antagonist, 7
      chlorokynurenic acid, on the induction of long-term potentiation at the
      commissural-CA1 synapse in anesthetized rats. Robust long-term potentiation of
      population excitatory postsynaptic potentials and population spike responses
      recorded extracellularly in the stratum pyramidale and in stratum radiatum of CA1
      developed after high frequency stimulation (100 Hz for 1 s) of commissural fibers
      during continuous intrahippocampal administration of vehicle solution (0.15 M
      NaCl). In contrast, infusion of either 7-chlorokynurenic acid (400 microM) or of
      the N-methyl-D-aspartate receptor antagonist, D-2-amino-5-phosphonovaleric acid
      (100 microM), significantly attenuated or completely blocked the development of
      long-term potentiation. When 7-chlorokynurenic acid was infused together with the
      glycine analog, D-serine (1 mM), long-term potentiation developed that was
      comparable to that observed in control animals. Intrahippocampal administration
      of D-serine alone was associated with slightly greater magnitude of long-term
      potentiation than observed in control animals. Collectively, these findings
      establish that in intact hippocampus, activity at the glycine modulatory site is
      necessary for activation of the N-methyl-D-aspartate receptor complex.
      Furthermore, these results suggest that the glycine modulatory site may not be
      fully saturated in vivo, and thus can serve to regulate N-methyl-D-aspartate
      receptor function.

PMID- 1347650
TI  - Brainstem excitatory amino acid receptors in nociception: microinjection mapping
      and pharmacological characterization of glutamate-sensitive sites in the
      brainstem associated with algogenic behavior.
AB  - In awake, freely moving rats, the intracerebral administration of the excitatory
      amino acid L-glutamate (30 nmol/0.5 microliters) into discrete regions of the
      brainstem resulted in a transient and spontaneous pain-like syndrome
      characterized by an initial vocalization and vigorous escape behavior. Systematic
      microinjection mapping studies were carried out at sites distributed caudally
      from the lower medulla and rostrally into diencephalon. These studies revealed
      that the spontaneous pain-like behavior was observed to occur after glutamate
      injection in 13% of 331 microinjected sites, and these sensitive sites were
      largely limited to the mesencephalic periaqueductal gray matter. The behavioral
      syndrome was dose-dependent and antagonized in a dose-dependent fashion by the
      glutamate receptor antagonists MK 801 and DL-2-amino-5 phosphonovalerate but not
      by gamma-D-glutamyl-amino-methylsulfonic acid. The pain-like behavior was also
      produced by the other excitatory amino acid receptor agonists N-methyl-D
      aspartate, quisqualate and to a certain extent by kainate in a dose-dependent
      manner with the order of potency being N-methyl-D-aspartate = kainate greater
      than quisqualate greater than D-glutamate. The effects of N-methyl-D-aspartate
      and quisqualate were antagonized by MK 801 and DL-2-amino-5 phosphonovalerate but
      not by gamma-D-glutamyl-amino-methylsulfonic acid. It is suggested that the pain
      like behavioral syndrome is the result of focal occupation of N-methyl-D
      aspartate receptors on neuronal populations in the terminal regions of rostrally
      projecting spinomesencephalic systems.

PMID- 1347651
TI  - Tachykinins and calcitonin gene-related peptide as co-transmitters in local motor
      responses produced by sensory nerve activation in the guinea-pig isolated renal
      pelvis.
AB  - Electrical field stimulation of circular muscle strips from the guinea-pig
      isolated renal pelvis produces a frequency-dependent positive inotropic effect of
      the spontaneous contractions which is unaffected by atropine and guanethidine and
      abolished by tetrodotoxin or in vitro capsaicin desensitization. Omega conotoxin
      fraction GVIA markedly inhibited the response to low frequencies of stimulation
      but had only a partial or minor inhibitory effect at higher frequencies.
      Tachykinins produce a concentration-dependent positive inotropic effect,
      neurokinin A being more potent than substance P. On the other hand, rat alpha
      calcitonin gene-related peptide (CGRP) inhibited spontaneous contractions of the
      renal pelvis. MEN 10,376 a neurokinin A (4-10) analog, antagonized the positive
      inotropism produced by neurokinin A, without affecting the response to KCl, and
      suppressed the positive inotropic response produced by electrical field
      stimulation. In the presence of MEN 10,376, a negative inotropic response was
      produced by electrical field stimulation which was antagonized by the C-terminal
      fragment (8-37) of human alpha calcitonin gene-related peptide (hCGRP). hCGRP (8
      37) antagonized the negative inotropic effect of exogenously administered CGRP
      without affecting inhibition by isoprenaline. Application of capsaicin (10
      microM) produced a marked increase in the outflow of substance P-, neurokinin A-
      and CGRP-like immunoreactivities from the superfused guinea-pig renal pelvis.
      Substance P-, neurokinin A- and CGRP-like immunoreactivities were also detected
      in tissue extracts of the renal pelvis by radioimmunoassay. These experiments
      indicate that peptide release from peripheral endings of capsaicin-sensitive
      primary afferents represents the major type of nerve-mediated response affecting
      motility of the guinea-pig isolated renal pelvis. Tachykinins and CGRP act as
      physiological antagonists and the excitatory action of tachykinins prevails over
      the inhibitory action of CGRP. Local modulation of renal pelvis motility by
      sensory nerves could facilitate removal of irritants present in the urine,
      protecting the kidney during obstruction and ureteral antiperistalsis.

PMID- 1347652
TI  - Analysis of extrathalamic synaptic influences on reactions of sensorimotor
      cortical neurons during conditioning.
AB  - The effects of iontophoretic application of acetylcholine, noradrenaline,
      serotonin and their blockers on neuronal activity were studied in the cat before
      and during fulfillment of conditioned instrumental placing reflex. It was found
      that acetylcholine increased the background neuronal activity through muscarinic
      cholinergic receptors and noradrenaline decreased it through beta-adrenoceptors
      in a considerable proportion of the cortical neurons. Serotonin had no reliable
      effect on the background activity. At the same time, it facilitated an initial
      component of the impulse reaction to conditioned stimulus and part of the impulse
      reaction preceding the start of the conditioned movement. Acetylcholine applied
      iontophoretically also facilitated the evoked responses in some cortical neurons
      via nicotinic cholinergic receptors. On the contrary, iontophoretic application
      of noradrenaline or ephedrine decreased the evoked activity of some neurons.
      Application of beta-adrenergic receptor blocker, propranolol, led to an increase
      of neuronal responses to conditioned stimuli. Evidently, noradrenergic
      projections exert a steady inhibitory influence on the cortical neurons during
      natural functioning of the cortex. It is concluded that cortical reactions evoked
      by activation of thalamic projections and intracortical connections are modulated
      and regulated by extrathalamic projections to the cortex.

PMID- 1347653
TI  - Long-term management of the patient with stable angina.
AB  - Advances in the pharmacologic, medical, and surgical treatment of ischemic heart
      disease have led to the recognition of new goals in the treatment of patients
      with stable angina, including the relief of symptoms, treatment of underlying
      causes, and the enhancement of their quality of life. As research continues to
      provide more information about the pathophysiologic process of ischemic heart
      disease, new procedures, diagnostics, and management techniques will continue to
      emerge. In considering the long-term management of patients with stable angina,
      the primary role of the nurse is in providing relevant information regarding the
      management of anginal symptoms and related lifestyle modifications. Integrating
      knowledge of the disease process and its treatment into nursing practice will
      achieve a comprehensive plan of nursing care that addresses the physiologic,
      psychosocial, and educational needs of the patient and family members.

PMID- 1347654
TI  - Drug treatment of COPD. Controversies about agents and how to deliver them.
AB  - Anticholinergics (in particular, ipratropium bromide [Atrovent]) are first-line
      therapy in patients with chronic obstructive pulmonary disease (COPD). Although
      more studies are needed to support the use of combination therapy, adding an
      inhaled beta agonist to the therapeutic regimen is reasonable in patients who
      remain symptomatic and need quick relief. Patients frequently receive inadequate
      amounts of drug with standard doses delivered by metered-dose inhalers, often as
      the result of improper technique, so symptomatic patients may require higher
      doses. Caution is recommended when the dose of inhaled sympathomimetics is
      increased in COPD patients with ischemic heart disease or tachyarrhythmias. The
      addition of an oral sympathomimetic is seldom necessary. Theophylline may be
      considered in outpatients who remain symptomatic despite their use of inhaled
      bronchodilators, but heart disease, seizure disorders, and gastroesophageal
      reflux are contraindications. Corticosteroid therapy remains controversial but
      can be helpful in patients who still have severe disease despite maximum
      bronchodilator therapy. Antibiotics can be of benefit in COPD patients undergoing
      an exacerbation who have increasing dyspnea, cough, and phlegm production.

PMID- 1347655
TI  - Foot wounds in diabetic patients. A comprehensive approach incorporating use of
      topical growth factors.
AB  - Managing nonhealing foot wounds in diabetic patients requires an understanding of
      the wounds' multiple contributing causes, including neuropathy, vascular
      occlusive disease, infection, and impaired wound healing. Proper attention to
      each cause may require consultations with vascular or orthopedic surgeons,
      diabetic education nurses, podiatrists, orthotists, and pedorthists. Wounds that
      fail to heal may respond to topical application of growth factors as part of a
      comprehensive clinical approach to the diabetic foot wound. An aggressive
      approach to diagnosis and treatment can result in improved wound healing and limb
      salvage.

PMID- 1347656
TI  - [Changes in plasma lipoproteins in Mediterranean boutonneuse fever].
AB  - We report 25 cases of boutonneuse fever with, in the acute phase, an increase of
      plasma transaminases, triglycerides and apoprotein B levels, a decrease of total,
      HDL and LDL cholesterol and a decrease of apoprotein A. These changes disappeared
      1 to 4 weeks after the beginning of treatment. They might be due to a reduced
      activity of lecithin-cholesterol acetyltransferase and lipoprotein lipase,
      probably caused by the hepatic and vascular disorders frequently found in this
      disease.

PMID- 1347657
TI  - Time-dependent alterations of leukotriene production and catabolism in rat
      peritoneal macrophages following intraperitoneal injection of thioglycollate
      broth.
AB  - Alterations of leukotriene (LT) productivity in peritoneal macrophages (PM) from
      untreated rats (control) as well as from rats treated i.p. with thioglycollate
      broth (TG) were investigated on days 3, 7 and 14 after TG administration. The
      resident PM from the untreated rats produced mainly LTB4 and 5-HETE with small
      amounts of 12-HETE and LTD4 with only a trace of LTC4 when stimulated with the
      calcium ionophore A23187. The PM elicited from rats on days 3 and 7 produced more
      LTC4 than did the resident PM but fewer other lipoxygenase metabolites. On day
      14, however, the elicited PM resembled the resident PM in terms of lipoxygenase
      metabolite production. Similar results were achieved in the presence of
      arachidonic acid and A23187. A decrease in lipoxygenase metabolism in the
      elicited PM was also suggested by using opsonized zymosan. Catabolism studies
      indicated a reduction in r-glutamyl transpeptidase activity in the elicited PM
      and suggested a reduction in catabolism for LTB4 in the former cells. The authors
      conclude that the TG-elicited PM generate fewer lipoxygenase metabolites than the
      resident PM following stimulation, but show a preferential conversion of LTA4 to
      sulfidopeptide LTs rather than to LTB4. The elicited PM also show a reduced
      catabolism for LTC4 and LTB4.

PMID- 1347658
TI  - Efficacy of moclobemide in different patient groups: a meta-analysis of studies.
AB  - Whilst tricyclic antidepressants are efficacious in all depressive syndromes,
      classical MAO-inhibitors differ substantially from them in their action. They are
      considered less effective in general and not very effective in endogenous
      depression, but recommended for the treatment of 'atypical' depression. A new
      class of RIMA (Reversible Inhibitors of MAO-A) represented by moclobemide
      requires a change in clinical thinking on antidepressants. Moclobemide shows the
      same efficacy in depression as tricyclics: its effects are similar in unipolar
      and bipolar affective disorders, and in patients with major depressive episode
      superimposed on dysthymia (double depression). As with classical antidepressants,
      the response rate tends to be lower, but is still present in psychotic
      depression. Agitated depressives do not respond less well than non-agitated
      patients to moclobemide. Patients meeting DSM-III-R criteria for major depression
      with melancholia tend to respond better than non-melancholics, but this may be
      associated with the significantly higher baseline severity observed in
      melancholics. A slightly higher response rate in patients without concomitant
      benzodiazepine treatment, compared to those with benzodiazepine comedication, may
      also be related to baseline differences in the severity of depression. Elderly
      depressives respond less well than younger patients to classical antidepressants,
      but with moclobemide, elderly patients do as well as younger ones.

PMID- 1347659
TI  - Biochemical effects of high single doses of moclobemide in man: correlation with
      plasma concentrations.
AB  - The effects of high single doses of moclobemide (300, 450 and 600 mg given at the
      end of a standardized meal) on plasma levels of several catecholamines and their
      deaminated metabolites, and on plasma levels of pituitary hormones were
      determined in eight healthy young male volunteers in a randomized, double-blind,
      placebo-controlled study. Assessment of the i.v. tyramine potentiation and
      determination of the plasma levels of moclobemide were also performed. The
      tyramine sensitivity factor at 2 h after dosing was about 2.1, with no
      significant differences between the doses used. The inhibitory activity of
      moclobemide on MAO-A was reflected in significant reductions of plasma
      concentrations of DHPG and 5-HIAA. No clear differences were detected between the
      moclobemide doses. Prolactin plasma concentrations were only slightly increased
      after the two higher doses. The plasma concentrations of moclobemide were very
      much in agreement with those found in previous studies under similar experimental
      conditions. Thus, single oral doses of 300, 450 and 600 mg moclobemide
      demonstrated marked inhibition of MAO-A activity, whereas a single dose of 300 mg
      induced a near-maximum effect.

PMID- 1347660
TI  - [Involvement of FGF-FGF receptor paracrine system and homeobox gene products in
      the formation of axial mesodermal structures in Xenopus embryos].

PMID- 1347661
TI  - Forensic DNA typing.

PMID- 1347662
TI  - Specific acceptance of cardiac allograft after treatment with antibodies to ICAM
      1 and LFA-1.
AB  - An indefinite survival of cardiac allografts between fully incompatible mice
      strains was observed when monoclonal antibodies (MAbs) to intercellular adhesion
      molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) were
      simultaneously administered after the transplantation for 6 days. Mice with long
      term surviving cardiac allografts accepted skin grafts from the donor-strain but
      rejected skin grafts from a third-party strain. Because MAbs to ICAM-1 or LFA-1
      alone were insufficient for prolonged tolerance, the two MAbs probably acted
      synergistically to induce specific unresponsiveness. Thus, ICAM-1----LFA-1
      adhesion participates in the induction of allograft rejection and MAbs may be
      useful as therapeutic agents.

PMID- 1347663
TI  - Barrett's esophagus: observations on diagnosis and management.
AB  - Barrett's esophagus is a premalignant condition that may often pass unrecognized
      in clinical practice. In adults, this condition is generally believed to be
      caused by chronic gastroesophageal reflux resulting in a metaplastic change in
      the epithelium of the esophagus. Diagnosis of Barrett's esophagus is established
      by careful biopsy of the involved esophageal mucosa. Periodic surveillance is
      recommended because of the risk of carcinoma. Antireflux surgery has not been
      shown to result consistently in the regression of the metaplastic epithelium, but
      potent acid suppression offers a new therapeutic approach that leads to healing
      of esophagitis and the potential regression of Barrett's epithelium.

PMID- 1347665
TI  - Subdural empyema complicating bacterial meningitis in a child: enhancement of
      membranes with gadolinium on magnetic resonance imaging in a patient without
      enhancement on computed tomography.
AB  - Subdural empyema is a known yet infrequent complication of bacterial meningitis.
      Subdural effusions occur frequently with meningitis in children and usually
      resolve spontaneously or with subdural taps. Subdural empyema should be suspected
      when a patient fails to respond to antibiotic therapy or worsens neurologically.
      Computed tomography (CT) scans with contrast often show enhancement of subdural
      collections when an empyema exists. However, this is not true all of the time. We
      present a case of subdural empyema complicating bacterial meningitis in a 4 month
      old in which CT enhancement was not present yet magnetic resonance imaging (MRI)
      scans with gadolinium demonstrated intense enhancement. For comparison, we
      present a second case of a child with sterile subdural effusions due to
      meningitis that demonstrates an absence of contrast enhancement on MRI studies.
      MRI scans with contrast may offer a more sensitive means of making an early
      diagnosis of subdural empyema.

PMID- 1347664
TI  - A single base change at a splice acceptor site leads to a truncated CAD protein
      in Urd-A mutant Chinese hamster ovary cells.
AB  - We have previously reported the isolation and characterization of mutant Chinese
      hamster ovary (CHO-K1) cells of the Urd-A complementation group, which require
      uridine for growth, are deficient in the activities of the first three enzymes of
      de novo UMP biosynthesis, and produce markedly reduced amounts of a truncated
      form of the multifunctional protein CAD, which contains these three enzyme
      activities. We report here that a single base change of G to A at a highly
      conserved RNA splice acceptor site is responsible for the phenotype of this
      mutant. In addition to a small amount of apparently normal CAD mRNA, this
      mutation causes production of two alternative forms of CAD mRNA in the mutant,
      one that includes the intron just prior to the mutation and one that excludes the
      exon just after the mutation. The affected splice site is located at the intron
      exon boundary just preceding the exon that encodes the beginning of the aspartate
      transcarbamylase (ATCase) domain of the CAD protein. Both intron inclusion and
      exon exclusion during RNA processing introduce a translation stop codon upstream
      of the region encoding this domain, resulting in the production of the truncated
      CAD protein seen in the Urd-A mutant. This mutation also results in markedly
      decreased levels of CAD mRNA and protein in the mutant.

PMID- 1347667
TI  - Kinetics of HIV-1 interactions with sCD4 and CD4+ cells: implications for
      inhibition of virus infection and initial steps of virus entry into cells.
AB  - The mechanisms of human immunodeficiency virus (HIV-1) entry into CD4+ cells and
      HIV-1 inactivation by sCD4 were studied by analyzing the kinetics of inhibition
      of viral infection by sCD4 and the kinetics of fusion of CD4+ cells with intact
      virions labeled with the lipid fluorophore octadecylrhodamine (R18). sCD4
      inhibited HIV-1 infection much more effectively when preincubated with virus
      prior to interaction with CD4+ cells than when mixed simultaneously with virions
      and cells. The kinetics of inhibition of infection was much slower at 4 degrees
      and at low sCD4 concentrations than at 37 degrees and at high sCD4
      concentrations. In the absence of sCD4, attachment of virus to cells leading to
      productive infection occurred within 10-30 min. Fusion of the virions with cells
      started after a 1-2 min lag time and was complete within 15 min. In high-density
      cell suspensions (5 x 10(7) cells/ml), even very high sCD4 concentrations (100
      micrograms/ml) failed to block viral infection during simultaneous mixing of
      cells, sCD4 and HIV-1. We conclude that the kinetics of sCD4-virus interaction
      and the competition of sCD4 with the cell surface associated CD4 for the virus
      are crucial factors in the inhibition of HIV-1 infection by sCD4. These results
      provide insight into mechanisms of viral penetration into cells and should be
      considered when designing new approaches for AIDS therapy.

PMID- 1347666
TI  - Changes in mononuclear peripheral blood cells in cattle with foot-and-mouth
      disease.
AB  - The percentages and absolute numbers of mononuclear peripheral blood cells (MNC)
      were studied in vaccinated (Vac) and non-vaccinated (control) cattle, challenged
      with foot-and-mouth disease virus (FMDV). All Vac cattle but none of the controls
      resisted challenge. Cell populations were studied immediately before and one week
      after challenge, by direct and indirect immunofluorescence, using polyclonal and
      monoclonal antibodies against different bovine markers. Total B-lymphocytes, as
      assessed with polyclonal anti-IgG (H + L) antisera, as well as total mononuclear
      cells, were normal before and after infection, and did not change in Vac or
      control groups. Before challenge Vac cattle had higher numbers of ILA-29+ (a
      putative marker for null cells or, alternatively, for gamma delta T-cells) than
      control cattle. After challenge, in control cattle, the number of total T-cells,
      BoT4-bearing (helper) T-cells and BoT8-bearing (cytotoxic/suppressor) T-cells
      were decreased, while IgM-bearing B-lymphocytes, as well as monocyte/macrophage
      cells were increased. The number of IL-A29-bearing T-cells did not change after
      infection in either group. After challenge, Vac cattle also showed increased
      numbers of IgM-bearing B-lymphocytes and monocyte/macrophage cells, whereas T
      subpopulations did not change significantly.

PMID- 1347668
TI  - Immune response to a murine coronavirus: identification of a homing receptor
      negative CD4+ T cell subset that responds to viral glycoproteins.
AB  - The lymphocyte proliferative response to mouse hepatitis virus, strain JHM (MHV
      JHM), a well-described cause of chronic and acute neurological infections, has
      been studied using vaccinia virus recombinants expressing individual MHV
      proteins. The surface (S) and transmembrane (M) glycoproteins were the most
      active proteins in causing proliferation of lymphocytes isolated from immunized
      adult mice, whereas lymphocytes from persistently infected mice proliferated only
      in response to the S protein. The cells from immunized mice which proliferated
      most actively in response to MHV were positive for the CD4 antigen and secreted
      interferon-gamma. In addition, the most responsive subset of cells did not
      express gp90MEL-14, the lymph node-specific homing receptor. The results identify
      a subpopulation of CD4+ T cells that may be an important component of the cell
      mediated immune response to this virus. The data also suggest that response to
      the M protein is important in preventing disease progression in C57BL/6 mice
      since cells which recognize this protein are absent from persistently infected
      mice.

PMID- 1347669
TI  - Mechanisms of tetrazepam action on spasticity.
AB  - This investigation assessed the mechanisms of Tetrazepam action on spasticity
      using a battery of electromyographic methods. Thirty patients with post-stroke
      spastic hemiparesis treated with Tetrazepam took part in the investigation. A
      questionnaire for assessment of subjective improvement after treatment used a 5
      point scale. The 5-point scales were used to assess muscle tone, muscle strength
      and tendon reflexes. A battery of electromyographic methods was used to analyse
      different mechanisms of spasticity: for alpha-motoneuron activity--the F-wave
      parameters; for gamma-motoneuron activity--the TA/H amplitude ratio; for
      presynaptic inhibition--the ratio of H-reflex maximal amplitudes before and after
      vibration on the Achilles tendon (Hvibr/Hmax); for common interneuron activity-
      the flexor reflex parameters. Our results revealed that Tetrazepam reduces tone
      in spastic muscles and has a slight effect on tendon hyperreflexia. It has no
      influence on muscle strength, Babinski sign and ankle clonus. Tetrazepam acts by
      decreasing motoneurone activity and increasing presynaptic inhibition.

PMID- 1347670
TI  - Effects of antipsychotic drugs on memory functions of schizophrenic patients.
AB  - In this research we investigated the effects of 4 antipsychotic drugs with
      different anticholinergic components on different memory functions of
      schizophrenic patients. Drugs were administered in cumulative doses and memory
      was tested 90 min after each drug was administered. The results show that
      chlorpromazine and thioridazine impaired short-term verbal memory after 6 h of
      sequential administration. Trifluoperazine and haloperidol improved short-term
      verbal memory from the third to the fifth administration. Immediate memory, long
      term memory and visual short-term memory were not impaired by any drug.

PMID- 1347671
TI  - Molecular genetic characterization of CNS tumor oncogenesis.

PMID- 1347672
TI  - G protein-controlled signal transduction pathways and the regulation of cell
      proliferation.

PMID- 1347674
TI  - Characterization of the endocrine cells in the pancreatic-bile duct system of the
      rat.
AB  - Six types of endocrine cells showing immunolabelling against gut or pancreatic
      islet hormones were identified in the pancreatic-bile duct system of the normal
      adult rat at the light and electron microscopic levels. They were located within
      the epithelial lining of the duct system from the intercalated portion to its
      duodenal opening. However, the distribution and frequency of each endocrine cell
      varied along the length of the duct system. While insulin, glucagon,
      somatostatin, and pancreatic polypeptide cells were widely distributed along the
      entire duct system, small numbers of cholecystokinin and serotonin cells were
      confined to the terminal portion. A considerable number of somatostatin cells
      were concentrated in gland-like pouches of the terminal portion of the common
      pancreatic-bile duct. When the accessory pancreatic duct was present, insulin,
      glucagon, and somatostatin cells were also found in its epithelial lining.
      Electron microscopically, the specific content of the secretory granules of all
      endocrine cells was confirmed by immunolabelling or cytochemical staining.
      Further the characteristics of the secretory granules of each endocrine cell type
      corresponded to those present in the same kind of endocrine cells in gut or
      pancreatic islet. The duct endocrine cells displayed a particular ultrastructural
      appearance. The "open type cells" were highly polarized, with their apical
      cytoplasmic process reaching the duct lumen, whereas "closed type cells" showed
      long basal cytoplasmic processes with no connection with the duct lumen. In
      general, insulin, and somatostatin cells were of the "open type", while no
      morphological connection with the duct lumen was found for glucagon and
      pancreatic polypeptide cells. The presence of various duct endocrine cells with
      their particular ultrastructural appearance implies that they may take part in
      modulating the function of the duct system.

PMID- 1347673
TI  - Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord
      tissue.
AB  - Expression of proteins associated with immune function was investigated
      immunohistochemically in postmortem brain and spinal cord of patients with
      amyotrophic lateral sclerosis (ALS). Reactive microglia/macrophages displaying
      high levels of leukocyte common antigen (LCA), the immunoglobulin receptor Fc
      gamma R1, lymphocyte function associated molecule-1 (LFA-1), the complement
      receptors CR3 and CR4, the class II major histocompatibility complex molecules
      HLA-DR, HLA-DP and HLA-DQ and common determinants of the class I HLA-A,B,C
      complex were abundant in affected areas in ALS. These areas included the primary
      motor cortex, motor nuclei of the brain stem, the anterior horn of the spinal
      cord, and the full extent of the corticospinal tract. A significant number of T
      lymphocytes of the helper/inducer (CD4+) and cytotoxic/suppressor (CD8+) subtypes
      were observed marginating along the walls of capillaries and venules and
      extending into the parenchyma of affected areas. Clusters of complement activated
      oligodendroglia as well as degenerating neurites positive for C3d and C4d were
      frequently detected in ALS-affected areas. These data provide evidence of immune
      effector changes in ALS. They are consistent with an autoimmune or slow virus
      theory of the disorder, but may reflect only secondary changes.

PMID- 1347676
TI  - Regular inhaled beta-adrenergic agonists in the treatment of bronchial asthma.

PMID- 1347675
TI  - Cetirizine does not influence the immune response.
AB  - Antihistamines are frequently employed in the treatment of allergic rhinitis and
      urticaria-angioedema syndrome. We analyzed the in vitro effects of cetirizine on
      the immune response. To this end the proliferation of peripheral mononuclear
      cells induced by mitogen and by -CD3, -CD2, or -CD28 monoclonal antibodies has
      been studied. Since the plasma peak of cetirizine following ingestion of 10 mg is
      about 1 microgram/mL, the drug was tested in the cultures at the concentration of
      0.1, 1, or 10 micrograms/mL. No influence of cetirizine on T cell proliferation
      was detected. We also evaluated the effect of cetirizine on the expression of the
      following markers expressed by T cells upon activation: lymphocyte markers ICAM
      1, HLA-DR, and CD25 surface expression, alpha-1-acid glycoprotein has been also
      studied. There was no effect of cetirizine on the investigated immunologic
      parameters; these data acquire clinical relevance when related to previous
      reports showing a depression of the immunologic response exerted by other
      compounds such as ketotifen and theophylline and when related to the recent data
      about the modulation of ICAM-1 expression on eosinophils by cetirizine.
      Cetirizine does not affect ICAM-1 expression of lymphocyte membrane.

PMID- 1347677
TI  - Where do we stand on drug treatment for ulcerative colitis?

PMID- 1347678
TI  - Level of blood pressure and risk of myocardial infarction among treated
      hypertensive patients.
AB  - To examine the association between the level of treated blood pressure and the
      incidence of myocardial infarction, we conducted a population-based case-control
      study of 912 members of a health maintenance organization who were receiving
      standard clinical treatment for hypertension. We found a J-shaped relationship
      between the most recently measured diastolic blood pressure and the risk of
      myocardial infarction, the lowest risk occurring at 84 mm Hg. The relative risk
      of myocardial infarction at 60 mm Hg was 2.07 (95% confidence interval, 0.86 to
      5.01), and at 100 mm Hg, 1.45 (95% confidence interval, 1.02 to 2.06). Treated
      systolic pressure bore a linear relationship to the risk of infarction. We
      conclude that the optimum target range for diastolic blood pressure in
      hypertensive patients may be 84 to 90 mm Hg. Levels outside this range may be
      associated with increased risk of myocardial infarction.

PMID- 1347679
TI  - Aerobic fitness and hormonal responses to prolonged sleep deprivation and
      sustained mental work.
AB  - This study examined the influence of aerobic fitness on the responses of selected
      hormones to the combined stressors of sleep deprivation (SD) and sustained mental
      work. Six aerobically high fit (HF) (VO2max greater than 50 ml.kg-1.min-1) and
      six average fit (AF) (VO2max less than 40 ml.kg-1.min-1) female subjects were
      subjected to a period of sleep loss of 60 h during which time they performed
      sustained mental tasks with no physical activity component. Venous blood samples
      were drawn every 12 h at 1330 hours and 0130 hours and plasmas analyzed for
      cortisol, growth hormone (hGH), prolactin, thyroxine (T4), triiodothyronine (T3),
      and reverse-triiodothyronine (rT3). For cortisol, both the HF and AF groups
      exhibited the normal high-daytime and low-nighttime pattern of secretion, with
      levels increasing significantly as the duration of SD increased. The normal
      elevations of hGH and prolactin levels during normal sleep were suppressed during
      SD. No significant fitness effects were found for cortisol, hGH, and prolactin
      responses. Plasma levels of T4, T3, and rT3 increased significantly during SD,
      with highly fit subjects exhibiting higher levels of these hormones than those of
      average fitness. We suggest that aerobic fitness may influence the peripheral
      metabolism of T4 during SD, but that aerobic fitness does not influence the
      regulation of the classical stress hormones during SD.

PMID- 1347680
TI  - Effect of L-glutamate on 2-oxoglutarate decarboxylase in Euglena gracilis.
AB  - The effect of tricarboxylic acid-cycle intermediates and related compounds on 2
      oxoglutarate decarboxylase activity was investigated. The addition of L-glutamate
      to Euglena cells grown on glucose/(NH4)2SO4 medium resulted in an increase in 2
      oxoglutarate decarboxylase activity, which was abolished by the simultaneous
      addition of cycloheximide. Immunochemical titration, immunoblot analysis and
      labelling in vivo with antibody raised against 2-oxoglutarate decarboxylase
      showed that the increase in 2-oxoglutarate decarboxylase activity was due to
      synthesis of new protein and not to activation of pre-existing protein. The
      experimental results reported here demonstrate that L-glutamate is assimilated by
      the pathway, via 2-oxoglutarate, that consists of L-glutamate-oxaloacetate
      aminotransferase, 2-oxoglutarate decarboxylase and succinate semialdehyde
      dehydrogenase, rather than by the gamma-aminobutyrate shunt, consisting of L
      glutamate decarboxylase and gamma-aminobutyrate aminotransferase.

PMID- 1347681
TI  - A structural motif that defines the ATP-regulatory module of guanylate cyclase in
      atrial natriuretic factor signalling.
AB  - Atrial natriuretic factor (ANF)-dependent guanylate cyclase is a single-chain
      transmembrane-spanning protein, containing an ANF receptor and having catalytic
      activity. ANF binding to the receptor domain activates the catalytic domain,
      generating the second messenger cyclic GMP. Obligatory in this activation process
      is an intervening step regulated by ATP, but its mechanism is not known. Through
      a programme of site-directed and deletion mutagenesis/expression studies, we
      report herein the identity of a structural motif (Gly503-Arg-Gly-Ser-Asn-Tyr
      Gly509) that binds ATP and amplifies the ANF-dependent cyclase activity; this,
      therefore, represents an ATP-regulatory module (ARM) of the enzyme, which plays a
      pivotal role in ANF signalling.

PMID- 1347682
TI  - High blood pressure: hunting the genes.
AB  - High blood pressure is a disease of unknown cause. Family history of the disease
      indicates higher risk, but it is not known which genes are involved or how they
      interact with environmental influences to produce the disorder. Molecular biology
      offers an approach to problems that have not so far been solved by classical
      physiology or biochemistry. By analysing polymorphic variation in chromosome
      markers such as minisatellite sequences, or by restriction fragment polymorphism
      analysis of candidate genes, attempts are being made to link genetic variations
      with hypertension. In genetically hypertensive rats, hypertension is associated
      with a polymorphism of the renin gene and with other loci on chromosomes 10 and
      18. The role of these loci in human hypertension remains to be determined. Other
      genes such as sodium-lithium countertransport may be involved. Environmental
      factors such as stress or salt intake could influence the rate or timing of
      expression of certain genes and thus result in hypertension.

PMID- 1347683
TI  - Safety of pedestrians and cyclists.

PMID- 1347686
TI  - Therapy for genitourinary cancer.

PMID- 1347685
TI  - Propofol potentiates both pre- and postsynaptic effects of vecuronium in the rat
      hemidiaphragm.
AB  - We have measured twitch tension in response to train-of-four stimulation in rat
      isolated phrenic nerve-hemidiaphragm preparations. Propofol inhibited nerve
      evoked twitch tension, with 50% inhibition occurring at 420 (SD 29) mumol litre
      1. Although propofol 100 mumol litre-1 by itself had no effect on nerve evoked
      twitch tension, it potentiated the neuromuscular blocking effects of vecuronium.
      The decrease in train-of-four ratio with vecuronium was directly proportional to
      the degree of twitch inhibition, regardless of whether twitch was depressed by
      vecuronium alone or in combination with propofol. The finding that the train-of
      four ratio was a function of the degree of block, rather than simply a function
      of vecuronium concentration, indicates that propofol also contributed to train-of
      four fade and potentiated both pre- and postsynaptic effects of the neuromuscular
      blocker. The concentrations of propofol used in this study are much greater than
      human therapeutic blood concentrations, which are typically 25-35 mumol litre-1
      (4-6 micrograms ml-1) immediately after a bolus dose of 2 mg kg-1, suggesting
      that neither muscle weakness nor potentiation of vecuronium-induced neuromuscular
      block should be of concern at propofol concentrations occurring clinically.

PMID- 1347684
TI  - Differential effects of vecuronium on diaphragm and geniohyoid muscle in
      anaesthetized dogs.
AB  - We have examined the sensitivity of the geniohyoid, an upper airway dilating
      muscle, to vecuronium in 12 anaesthetized dogs undergoing mechanical ventilation
      of the lungs and compared it with that of the diaphragm. Dogs were allocated
      randomly to two groups: pentobarbitone alone (group 1, n = 7); pentobarbitone
      combined with 0.2 MAC (0.44%) of enflurane anaesthesia (group 2, n = 5).
      Supramaximal single twitch stimulations (0.1 Hz) were applied to the phrenic
      nerves in the upper thorax and the geniohyoid branches of the hypoglossal nerves
      at the neck. The evoked responses were assessed by the transdiaphragmatic
      pressure (Pdi) and the isometric force of the geniohyoid muscles (Tgh) until
      complete recovery of these variables after i.v. administration of vecuronium 0.02
      mg kg-1. In both groups, the magnitude of the depression of twitch response was
      greater and time required to reach control amplitude was longer in the geniohyoid
      than the diaphragm. The depression of Tgh was significantly greater in group 2
      than in group 1, whereas no change was observed in Pdi between the two groups. We
      conclude that the geniohyoid is more sensitive to vecuronium than the diaphragm
      and the differential effects of vecuronium are facilitated by a low concentration
      of enflurane.

PMID- 1347687
TI  - Genitourinary rhabdomyosarcoma in childhood: current treatment alternatives and
      controversies in management.

PMID- 1347688
TI  - Tumor necrosis factor and chemotherapeutic drugs targeted at DNA topoisomerase II
      for the treatment of genitourinary malignancies.
AB  - Recombinant TNF as a single agent for human cancer appears to be of limited
      value. However, rTNF has synergistic anticancer effects when combined with
      chemotherapeutic drugs targeted at DNA topoisomerase II. This effect of rTNF has
      been observed in several in vitro and in vivo tumor models, both in animal and
      human studies. The mechanism of this interaction appears to involve lesions to
      the DNA of tumor cells mediated by inhibition of DNA topoisomerase II. The
      combinations of rTNF plus doxorubicin and rTNF plus etoposide administered
      systemically are currently under evaluation by clinical trials in patients with
      advanced cancers. Determination of the efficacy of such combination therapy must
      await the completion of phase I and II trails. Other routes of administration
      that might increase the local concentration of rTNF and could be combined with
      topoisomerase II-targeted drugs include intravesical administration and the use
      of tumor-infiltrating lymphocytes.

PMID- 1347690
TI  - Suramin as an archetypical compound in the development of growth factor
      antagonists for inhibition of genitourinary tumors.

PMID- 1347691
TI  - Renal-sparing surgery for renal and transitional cell carcinoma.

PMID- 1347689
TI  - Cell motility as an index of metastatic ability in prostate cancers: results with
      an animal model and with human cancer cells.

PMID- 1347693
TI  - The role of radiotherapy following radical prostatectomy.

PMID- 1347692
TI  - A comparison of the treatment of metastatic prostate cancer by testicular
      ablation or total androgen blockade. The Canadian Anandron Study Group.

PMID- 1347694
TI  - Nuclear DNA ploidy and prostate cancer.

PMID- 1347695
TI  - Brachytherapy of localized penile carcinoma.

PMID- 1347696
TI  - Malignancy associated with urinary tract reconstruction using enteric segments.

PMID- 1347697
TI  - Evolving concepts in surgical management of testis cancer.

PMID- 1347698
TI  - Neoadjuvant chemotherapy and partial cystectomy for invasive bladder cancer.

PMID- 1347699
TI  - Papers from the Peripheral Vascular Surgical Society 1991 meeting.

PMID- 1347700
TI  - Cholinergic terminals in the cat visual cortex: ultrastructural basis for
      interaction with glutamate-immunoreactive neurons and other cells.
AB  - Acetylcholine (ACh) is one of the transmitters utilized by extra-thalamic
      afferents to modulate stimulus-driven neurotransmission and experience-dependent
      plasticity in the visual cortex. Since these processes also depend on the
      activation of glutamatergic receptors, cholinergic terminals may exert their
      effects via direct modulation of excitatory neurotransmission. The objective of
      this study was to determine whether the ultrastructural relationships between
      cholinergic terminals, glutamate-immunoreactive neurons, and other unlabeled
      cells support this idea. Sections from aldehyde-fixed visual cortex (area 17) of
      adult cats were immunolabeled for the following molecules: (1) choline
      acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme; (2) L-glutamate;
      or (3) ChAT simultaneously with L-glutamate by combining electron-microscopic
      immunogold and immunoperoxidase techniques. None of the cortical terminals were
      dually labeled, suggesting that (1) the labeling procedure was free of chemical
      or immunological cross reactions; and (2) glutamate immunoreactivity probably
      reflects the transmitter, and not metabolic, pool of L-glutamate. Comparisons
      between cholinergic and noncholinergic axons revealed that (1) ChAT
      immunoreactive axons formed fewer identifiable synaptic contacts within single
      ultrathin sections (P less than 0.01 using chi-square test); and (2) more of the
      cholinergic axons occurred directly opposed to other terminals (P less than
      0.0015 by chi-square test), including 21% of which resided directly across
      asymmetric, axo-spinous junctions. Dual labeling showed that a third of the
      synaptic targets for cholinergic terminals contained detectable levels of
      glutamate immunoreactivity. Some of the axo-spinous junctions juxtaposed to
      cholinergic axons also exhibited glutamate immunoreactivity presynaptically.
      These observations provide ultrastructural evidence for direct, cholinergic
      modulation of glutamatergic pyramidal neurons within the mammalian neocortex.
      Prevalence of juxtapositions between cholinergic terminals and axo-spinous
      synapses supports the following ideas: (1) ACh may modulate the release of
      noncholinergic transmitters, including Glu; (2) Glu may modulate ACh release; and
      (3) these processes may be concurrent with cholinergic modulation of
      glutamatergic synapses at postsynaptic sites.

PMID- 1347701
TI  - Identification of the active site residues in dipeptidyl peptidase IV by affinity
      labeling and site-directed mutagenesis.
AB  - The active site of dipeptidyl peptidase IV (DPPIV) was examined by chemical
      modification and site-directed mutagenesis. Purified DPPIV was covalently
      modified with [3H]diisopropyl fluorophosphate (DFP). The radiolabeled DPPIV was
      digested with lysyl endopeptidase, and the peptides were separated by high
      performance liquid chromatography. A single 3H-containing peptide was obtained
      and analyzed for amino acid sequence and radioactivity distribution. A comparison
      of the determined sequence with the predicted primary structure of DPPIV [Ogata,
      S., Misumi, Y., & Ikehara, Y. (1989) J. Biol. Chem. 264, 3596-3601] revealed that
      [3H]DFP was bound to Ser631 within the sequence Gly629-Trp-Ser-Tyr-Gly633, which
      corresponds to the consensus sequence Gly-X-Ser-X-Gly proposed for serine
      proteases. To further identify the essential residues in the active-site
      sequence, we modified the DPPIV cDNA by site-directed mutagenesis to encode its
      variants. Expression of the mutagenized cDNAs in COS-1 cells demonstrated that
      any single substitution of Gly629, Ser631, or Gly633 with other residues resulted
      in the complete loss of the enzyme activity and DFP binding. Although
      substitution of Trp630----Glu or Tyr632----Phe caused no effect on the enzyme
      activity, that of Tyr632----Leu or Gly abolished the activity. These results
      indicate that the sequence Gly-X-Ser-(Tyr)-Gly is essential for the expression of
      the DPPIV activity.

PMID- 1347702
TI  - Are proton symports in yeast directly linked to H(+)-ATPase acidification?
AB  - Transport of amino acids in Saccharomyces cerevisiae is an H(+)-driven secondary
      active transport. Inhibitors of the plasma membrane H(+)-ATPase, particularly
      heavy water, diethylstilbestrol and suloctidil, were shown to affect the H(+)
      extruding ATPase activity as well as the ATP-hydrolyzing activity, to a similar
      degree as they inhibited the transport of amino acids. The inhibitors had
      virtually no effect on the membrane electric potential or on the delta pH which
      constitute the thermodynamically relevant source of energy for these transports.
      Transport of acidic amino acids was affected much more than that of the neutral
      and especially of the basic ones. The effects were greater with higher amino acid
      concentrations. All this is taken as evidence that the amino acid carriers
      respond kinetically to the presence of protons directly at the membrane site
      where they are extruded by the H(+)-ATPase, rather than to the overall
      protonmotive force.

PMID- 1347703
TI  - Two alloalbumins with identical electrophoretic mobility are produced by
      differently charged amino acid substitutions.
AB  - We describe the amino acid substitutions of albumins Sondrio and Paris 2, two
      slow moving variants of human serum albumin, which show an identical
      electrophoretic mobility on cellulose acetate at three different pH values. These
      variants have been found in several instances in a wide geographic area including
      Northern Italy and France. Both alloalbumins were isolated from the sera of
      heterozygous subjects. Isoelectric focusing analysis of CNBr fragments from the
      purified variants allowed us to localize the mutation of albumin Sondrio in
      fragment CNBr V (residues 330-446) and that of albumin Paris 2 in CNBr VII
      (residues 549-585). Sequential analysis of the variant CNBr VII established the
      molecular defect of albumin Paris 2 as 563 Asp----Asn. Fragments CNBr V from
      normal and Sondrio albumins were isolated on a preparative scale and subjected to
      tryptic and V8 proteinase digestion. Sequence determination of the abnormal
      tryptic and V8 peptides revealed that the variant arises from the substitution of
      glutamic acid 333 by lysine. Thus, a +1 change in the C-terminal region of the
      albumin molecule produces a variant with the same electrophoretic mobility as an
      alloalbumin with a +2 substitution in the central domain, suggesting a higher
      degree of exposure to the solvent of the C-terminal tailpiece. Both amino acid
      substitutions are consistent with a G----A transition in the first position of
      the corresponding codon in the structural gene.

PMID- 1347704
TI  - ECT and neuroleptics as primary treatment for schizophrenia.

PMID- 1347705
TI  - Lack of association between an RFLP near the D2 dopamine receptor gene and severe
      alcoholism.
AB  - Blum et al (1990) have recently examined a restriction fragment length
      polymorphism (RFLP) detected by TaqI RFLP to the dopamine D2 receptor gene (DRD2)
      in deceased alcoholics and nonalcoholics, and reported an association between
      alcoholism and the A1 allele. Subsequent studies, however, by other investigators
      have failed to confirm this. We have examined the DRD2 TaqI RFLP in 47 living
      Caucasian males with severe alcoholism. All alcoholic subjects were thoroughly
      characterized by a structured interview, and met DSM-III-R criteria for alcohol
      dependence. Only 9/47 (19%) (1990) of these alcoholics had the AI allele compared
      to 14/22 (64%) reported by Blum et al. This rate was not significantly different
      from the rates reported in control populations by Blum et al (1990), CEPH, or
      Bolos et al (1990), and differed only slightly from those reported by Grandy et
      al (1990). Alcoholics selected for severe medical complications also displayed a
      similar rate. Our data do not support an association between alcoholism and the
      D2 dopamine receptor gene in this population.

PMID- 1347706
TI  - Protein CVermont: symptomatic type II protein C deficiency associated with two
      GLA domain mutations.
AB  - This study investigates type II protein C deficiency in a family with
      manifestations of both arterial and venous thrombosis. Of 64 members of the
      kindred, 14 have been tested and 7 have PC deficiency. Among affected individuals
      (n = 7), mean protein C levels by different assays were as follows: enzyme-linked
      immunosorbent assay (ELISA), 3.8 micrograms/mL (2.1 to 4.3 micrograms/mL);
      amidolytic with venom activator, 115% (60% to 140%); clotting with venom
      activator, 42% (23% to 59%). The mean ratio of clotting to amidolytic assays for
      the affected individuals was 0.37 compared with a normal range of 0.8 to 1.2.
      Thus, the affected individuals have normal total protein C and their activated
      protein C has a normal active site assessed by chromogenic substrate; however,
      they have markedly diminished clotting activity. Immunoassay and chromatography
      data suggested an abnormality of carboxylation in the gamma carboxyglutamic acid
      (Gla) domain. Polymerase chain reaction amplification and direct DNA sequencing
      of exon 2 from genomic DNA of affected individuals showed two nucleotide
      substitutions. One of the mutations (A----C) results in Glu20----Ala, thereby
      eliminating a site for vitamin K-dependent gamma-carboxylation. The other
      substitution (G----A) results in a Val34----Met mutation. DNA sequencing of the
      other exons from affected individuals has shown no further difference from that
      of the wild-type gene. The former mutation also removes a Bgl II restriction
      endonuclease site, which has allowed us to confirm the mutation in affected
      individuals by direct digestion and Southern hybridization of genomic DNA from
      family members. This is the first reported family with documented Gla domain
      mutations in the protein C gene.

PMID- 1347707
TI  - Absolute requirement of CD11/CD18 adhesion molecules, FcRII and the
      phosphatidylinositol-linked FcRIII for monoclonal antibody-mediated neutrophil
      antihuman tumor cytotoxicity.
AB  - We have previously shown that 3F8, a murine IgG3, monoclonal antibody (MoAb)
      specific for the ganglioside GD2, mediates tumor cell kill in vitro and in vivo.
      We now describe receptor requirements of polymorphonuclear leukocytes (PMN) in
      3F8-mediated cytotoxicity (ADCC) of human GD2 (+) melanoma and neuroblastoma cell
      lines. PMN from a child with leukocyte adhesion deficiency (LAD) were devoid of
      CD11/CD18 adhesion molecules and mounted no detectable ADCC. MoAb to CD11b,
      CD11c, and CD18 each efficiently blocked ADCC by normal PMN. In contrast, a panel
      of different MoAbs to CD11a had no significant inhibitory effect on ADCC, a
      finding consistent with the low-to-absent expression of the CD11a ligand,
      intercellular adhesion molecule-1, on the target cells. Granulocyte-macrophage
      colony-stimulating factor (GM-CSF) significantly increased the expression of
      CD11b, CD11c, and CD18 on normal PMN, decreased the expression of Fc receptors
      (FcR), and enhanced ADCC by normal but not by LAD PMN. MoAbs to FcRII and FcRIII
      each efficiently blocked ADCC; anti-FcRI MoAb had no effect. Flow cytometry using
      anti-FcRII MoAb versus anti-FcRIII MoAb did not show cross competition,
      suggesting that inhibition of ADCC was not a steric effect resulting from FcRII
      proximity to FcRIII. PMN deficient in FcRIII (obtained from patients with
      paroxysmal nocturnal hemoglobinuria) and PMN depleted of FcRIII by treatment with
      elastase or phosphatidylinositol (PI)-specific phospholipase C produced low ADCC,
      supporting a role for the PI-liked FcRIII. Thus, optimal ADCC using human PMN,
      human solid tumor cells, and a clinically active MoAb (conditions that contrast
      with the heterologous antibodies and nonhuman or nonneoplastic targets used in
      most models of PMN ADCC) required CD11b, CD11c, FcRII, and the PI-linked FcRIII.
      Furthermore, in this clinically relevant system, GM-CSF enhancement of antitumor
      PMN ADCC correlated with increased expression of CD11/CD18 molecules.

PMID- 1347708
TI  - High expression of the mdr3 multidrug-resistance gene in advanced-stage chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by an often indolent course
      with a poor therapeutic response at advanced stage. We investigated the
      expression of the human multidrug resistance genes mdr1 and mdr3 in 31 patients
      with CLL. Using specific probes for mdr1 and mdr3 mRNA, respectively, expression
      of both genes could be found in 29 of 31 patients. Of those, nine had high
      expression of mdr1 and 13 of mdr3. Although 29 of 31 patients showed coexpression
      of mdr1 and mdr3, the mRNA levels were not interrelated. Prior treatment did not
      significantly influence the level of mdr1 or mdr3 expression. In patients with
      advanced CLL (Rai stage 3 + 4) the mdr3 expression was significantly higher than
      in early-stage CLL (Rai stage 0 to 2) (mean +/- SEM, 25.4 +/- 4.2 U v 4.2 +/- 1.1
      U; P less than .0001). Such a difference was not present for mdr1 expression
      (21.5 +/- 4.3 U v 10.7 +/- 3.1 U; P = .09). These data indicate that advanced
      stage CLL is associated with an increased mdr3 expression, which may concur with
      a decreased sensitivity to chemotherapy.

PMID- 1347709
TI  - Chromosomal loss and deletion are the most common mechanisms for loss of
      heterozygosity from chromosomes 5 and 7 in malignant myeloid disorders.
AB  - We have examined a population of patients with acute myeloid leukemia (AML) or
      myelodysplastic syndrome (MDS) for loss of heterozygosity of polymorphic markers
      on chromosomes 5 and 7. The rationale for this study was the observation that the
      majority of patients with therapy-related leukemia (t-AML or t-MDS), resulting
      from cytotoxic treatment for prior malignancies, have loss of chromosome 5 and/or
      7 or deletions involving the long arms of one or both of these chromosomes. This
      cytogenetic finding suggested that tumor-suppressor genes, important in the
      development of AML, may be located in these chromosomal regions. We analyzed a
      total of 60 patients, 43 with primary MDS/AML de novo and 17 with t-MDS/t-AML.
      Leukemia cells were evaluated for restriction fragment length polymorphisms
      (RFLPs). Leukemia cell genotypes were compared with lymphoblastoid cell genotypes
      from the same patients. Two cases of loss of heterozygosity were identified from
      chromosomes lacking visible deletions: one involving chromosome 5 in a patient
      with AML de novo who had a visible deletion of 5q at a later stage of the
      disease, and one involving chromosome 7 in a patient with t-AML. We conclude that
      allele loss from loci on chromosomes 5 and 7 in MDS/AML, when it occurs, usually
      results from major deletion or simple chromosome loss, rather than from mitotic
      recombination or chromosome loss with duplication of the remaining homologue.

PMID- 1347710
TI  - CD11/CD18-independent neutrophil adherence to laminin is mediated by the integrin
      VLA-6.
AB  - Regulated adherence of polymorphonuclear leukocytes (PMNs) to endothelium and
      subendothelial matrix is a critical event for PMN localization at and migration
      into inflammatory sites. We previously reported that human PMNs stimulated in
      vitro adhere to laminin, the major glycoprotein of mammalian basement membrane,
      by both CD11/CD18 (beta 2 integrin)-dependent and CD11/CD18-independent
      mechanisms. This CD11/CD18-independent adherence is inhibited by monoclonal
      antibodies (MoAbs) directed against the beta 1 subunit of integrins (very late
      antigens [VLA]). The specific PMN VLA receptor responsible for stimulated
      CD11/CD18-independent PMN adherence to laminin was not elucidated. We show here
      that this CD11/CD18-independent adherence is mediated by a member of the beta 1
      integrins, VLA-6. MoAbs GoH3 and 450-30, which bind the alpha 6 subunit of VLA-6,
      significantly reduced adherence of phorbol myristate acetate-stimulated PMNs to
      laminin-coated surfaces when CD11/CD18-independent adherence was blocked with
      anti-CD11/CD18 MoAbs. Furthermore, GoH3 completely inhibited stimulated adherence
      of CD11/CD18-deficient PMNs to laminin. Analysis by flow cytometry showed that
      human PMNs express VLA-6. The PMN alpha 6 is identical in size and pl to the
      platelet alpha 6, but the PMN beta 1 exhibits considerable heterogeneity in
      molecular weight compared with the platelet beta 1. This activation-dependent
      adherence receptor for laminin may play a role in PMN interaction with basement
      membrane laminin during PMN movement through vascular walls.

PMID- 1347711
TI  - Management of elderly patients with sustained hypertension.
AB  - OBJECTIVE: To assess the clinical benefits of treating hypertension in elderly
      patients and to derive practical guidelines regarding indications, goals, and
      forms of treatment. DESIGN: Review of six published randomised trials. RESULTS:
      Active treatment of hypertension in elderly patients was associated with
      significant improvements in several indices of cardiovascular morbidity and
      mortality, particularly the incidence of fatal and non-fatal strokes. On the
      basis of the trial data, combined systolic and diastolic hypertension was defined
      as a sustained systolic pressure greater than 160 mmHg and diastolic pressure
      greater than 90 mmHg. There is convincing evidence that efforts should be made to
      reduce both systolic and diastolic pressures to below these levels in patients up
      to the age of 80 years. Isolated systolic hypertension was defined as a systolic
      pressure greater than 160 mmHg in the presence of a diastolic pressure less than
      90 mmHg. Two trials reported benefit from the treatment of isolated systolic
      hypertension in patients up to the age of 80, and further trials are underway to
      support or refute this recommendation. Diuretics have an established role in the
      management of hypertension in elderly patients; beta adrenoceptor antagonists
      have given variable results, and the benefits are less impressive than with
      diuretic based regimens. Newer agents show promise in the treatment of elderly
      patients, particularly in the presence of coexisting disease, but their effects
      on morbidity and mortality have not been evaluated in large randomised trials.
      CONCLUSIONS: Diuretics rather than beta blockers are the treatment of choice for
      patients with uncomplicated hypertension, but combinations of drugs may be
      required in as many as 50% of patients.

PMID- 1347712
TI  - When should asymptomatic patients with HIV infection be treated with zidovudine?

PMID- 1347713
TI  - Antifolding activity of hsp60 couples protein import into the mitochondrial
      matrix with export to the intermembrane space.
AB  - Cytochrome b2 reaches the intermembrane space of mitochondria by transport into
      the matrix followed by export across the inner membrane. While in the matrix, the
      protein interacts with hsp60, which arrests its folding prior to export. The
      bacterial-type export sequence in pre-cytochrome b2 functions by inhibiting the
      ATP-dependent release of the protein from hsp60. Release for export apparently
      requires, in addition to ATP, the interaction of the signal sequence with a
      component of the export machinery in the inner membrane. Export can occur before
      import is complete provided that a critical length of the polypeptide chain has
      been translocated into the matrix. Thus, hsp60 combines two activities: catalysis
      of folding of proteins destined for the matrix, and maintaining proteins in an
      unfolded state to facilitate their channeling between the machineries for import
      and export across the inner membrane. Anti-folding signals such as the
      hydrophobic export sequence in cytochrome b2 may act as switches between these
      two activities.

PMID- 1347715
TI  - Mitogen-induced liver hyperplasia does not substitute for compensatory
      regeneration during promotion of chemical hepatocarcinogenesis.
AB  - Experiments were designed to determine the efficacy of different types of liver
      cell proliferative stimuli given during exposure to several liver tumor-promoting
      regimens, on the formation of foci of enzyme-altered hepatocytes. Male Wistar
      rats were initiated with diethylnitrosamine (150 mg/kg body wt). After a 2 week
      recovery period animals were subjected to promoting regimens, the resistant
      hepatocyte model, the phenobarbital model and the orotic acid model. While the
      rats were on these regimens they were given liver cell proliferative stimulus,
      either a compensatory type (two-thirds partial hepatectomy or a necrogenic dose
      of carbon tetrachloride) or a direct hyperplastic stimulus such as that induced
      by the primary mitogen, lead nitrate. Initiated cells so promoted by these
      regimens were monitored as foci of enzyme-altered hepatocytes positive for gamma
      glutamyltransferase and placental glutathione S-transferase or deficient for
      adenosine triphosphatase. While carbon tetrachloride and partial hepatectomy
      induced compensatory regeneration stimulated the promoting ability of the
      regimens used, direct hyperplasia could not stimulate the formation of foci
      and/or nodules from initiated hepatocytes. Evaluation of thymidine incorporation
      indicated that there was no significant difference in the extent of DNA synthesis
      in both the proliferative stimuli irrespective of the promoting procedure used.

PMID- 1347714
TI  - Cyproterone acetate induces DNA damage in cultured rat hepatocytes and
      preferentially stimulates DNA synthesis in gamma-glutamyltranspeptidase-positive
      cells.
AB  - The synthetic anti-androgen and progestin cyproterone acetate (CPA) is known to
      increase the liver tumor rate in rats. The tumorigenicity of CPA has been
      attributed to a tumor-promoting activity of the steroid. In order to discover
      whether CPA acts directly on preneoplastic liver cells or via indirect effects,
      we investigated whether CPA stimulates replicative DNA synthesis in vitro in
      hepatocytes isolated from carcinogen-treated rats (two-thirds hepatectomy, 1 x 30
      mg diethylnitrosamine per kg and 0.1% phenobarbital in the drinking water) and
      whether the degree of stimulation differs in gamma-glutamyltranspeptidase (GGT)
      positive, putatively preneoplastic and GGT-negative, 'normal' hepatocytes. The
      possibility that CPA might also have initiating potential was investigated by
      studying its effects on DNA repair synthesis. Stimulation of [3H]thymidine
      incorporation into the DNA by CPA was only observed in the presence of epidermal
      growth factor (EGF) (10 ng/ml) and insulin (10 mU/ml). Maximal effects were
      obtained between 2 and 10 microM. DNA synthesis in the presence of EGF/insulin
      was reduced by the 'pure' anti-androgen flutamide, but stimulated by the 'pure'
      progestin promegestone. In the presence of CPA, EGF and insulin, the labelling
      index was twice as high in GGT-positive as in GGT-negative liver cells,
      regardless of whether mitogens were added at 48 or 72 h. The labelling index did
      not differ in the GGT-positive and negative hepatocytes when CPA was omitted.
      These findings are consistent with the idea that CPA has tumor-promoting
      activity. CPA significantly induced repair synthesis in the isolated hepatocytes
      from both untreated and carcinogen-treated rats. This increase was detected at a
      concentration as low as 2 microM and maximal effects were obtained at 20 microM.
      These results indicate that CPA is not only a tumor-promoting, but also a
      genotoxic chemical, i.e. that it might also have an initiating potential.

PMID- 1347716
TI  - Threshold dose dependence in phenobarbital promotion of rat hepatocarcinogenesis
      initiated by diethylnitrosamine.
AB  - The dose-response of phenobarbital (PB) promotion of hepatocarcinogenesis in rats
      was investigated. Male F344 rats were given 1, 4, 16, 75, 300 or 1200 p.p.m. PB
      solutions given ad libitum as their drinking water for 39 weeks following
      initiation with a single i.p. injection of diethylnitrosamine (DEN) (100 mg/kg).
      At week 40, the incidence of hepatic tumors was increased clearly in the DEN + PB
      groups given 300 p.p.m. PB or above, as compared to that in the group given DEN
      only. Linear dose-response curves for numbers and sizes of enzyme-altered hepatic
      foci (gamma-glutamyl-transpeptidase or placental glutathione S-transferase
      positive foci) were obtained in the dose range 16-1200 p.p.m. PB. The minimum
      promoting dose level of PB for enzyme-altered foci, estimated from dose-response
      curves by the Logit model, was calculated to be 15-23 p.p.m. Thus while dose
      dependence was demonstrated over a large range, a threshold was evident at low
      doses.

PMID- 1347718
TI  - Embryonic heart rate of the domestic fowl (Gallus domesticus) in a
      quasiequilibrium state of altered ambient temperatures.
AB  - 1. The heart rates (fH) of 12-day-old embryos (young), 16- and 18-day-old embryos
      (late) and of 20-day-old embryos (externally pipped eggs, EP) were measured
      noninvasively at a temperature of 38 degrees C and after a 5 hr exposure to an
      ambient temperature (Ta) within the range 34-46 degrees C. 2. All embryos
      survived the 5 hr exposure to Ta of 42 degrees C. The lethal Ta ranged from 44
      degrees C (EP eggs) to 46 degrees C (young embryos). 3. The temperature
      coefficient (Q10) of fH became smaller than 2 in EP eggs as Ta was decreased or
      increased from 38 degrees C, implying an incipient homeothermic response of fH.

PMID- 1347717
TI  - Heart rate and blood pressure changes during radiofrequency irradiation and
      environmental heating.
AB  - 1. Whole-body exposure of animals to radiofrequency radiation (RFR) can cause an
      increase in body temperature. 2. Responses to heating, whether due to RFR or to
      more conventional means, include changes in heart rate and blood pressure. 3.
      Although cardiovascular responses to various types of heating are similar,
      differences in the magnitude of changes may result from different thermal
      gradients within the body. 4. This review compares the effects of RFR and
      conventional environmental heating on heart rate and blood pressure.

PMID- 1347719
TI  - Comparative analysis of cell replacement in hibernators.
AB  - 1. Cell renewal in hibernators undergoes seasonal rhythm independent of the
      hibernation state. 2. We propose that seasonal depression of cell renewal in
      tissues of hibernators is caused by seasonal involution of thymus in these
      animals. 3. The latter is known to be involved in the control of cell
      proliferation. 4. The state of hibernation per se has also an effect on cellular
      proliferation. 5. It induces the block of cells in the permitotic phase. It is
      suggested that the blockage of cells in renewing tissues of hibernators under
      natural deep hypothermia throughout a period of torpidity represents the adaptive
      reaction of the organism.

PMID- 1347720
TI  - Comparative physiological responses to stressors in animals.
AB  - 1. The species-specific experimental response to stressors (SSERTS) analysis has
      been applied to a number of species under varied short and long term conditions.
      2. The measure provides quantitative data relating to the physiological responses
      of animals when exposed to stressors and results are presented comparing these
      for different methods of immobilization, euthanasia, etc. at intra- and inter
      species level. 3. It is suggested that the SSERTS measure is of greater value for
      measuring the responses of animals to stressors than is the measurement of the
      concentration of single blood variables.

PMID- 1347721
TI  - Decapitation or starvation raise haemolymph ecdysteroid titres in the
      ovoviviparous female cockroach, Blaberus craniifer Burm.
AB  - 1. Decapitating newly emerged Blaberus craniifer females near the prothorax
      severs connections between the suboesophageal and prothoracic ganglia, thus
      depriving them of the neuroendocrine cephalic complex (including brain and
      suboesophageal ganglion) and the anterior end of prothoracic glands (PGs). 2. As
      demonstrated by enzyme immunoassay (EIA), headless females have higher levels of
      ecdysteroids (ECDs) in haemolymph than starved or fed females, indicating that
      the neuroendocrine cephalic complex influences circulating ECD levels. 3. The
      time course of hormonal peaks in decapitated females resembles that in starved
      females during the first post-ecdysial week, suggesting that some as yet unknown
      regulating mechanism of ECD production lies outside the head. 4. It is suggested
      that: (a) The PGs are sites for ECDs production in the early post-imaginal
      period, (b) the prothoracic and suboesophageal ganglia (linked by nerves to PGs)
      regulate PGs activity, possibly via neural inputs.

PMID- 1347722
TI  - The effects of chronic exposure to elevated environmental temperature on
      intestinal morphology and nutrient absorption in the domestic fowl (Gallus
      domesticus).
AB  - 1. Exposure of growing broiler chickens to elevated environmental temperature (35
      degrees C) for two weeks, markedly reduced food intake (29%) and growth rate
      (37%) compared to birds maintained at 22 degrees C. 2. These changes in growth
      were accompanied by increased in vivo jejunal uptakes of galactose (36%) and
      methionine (50%) measured per unit intestinal dry weight. 3. Both the
      electrogenic (phloridzin sensitive) and non-electrogenic (phloridzin insensitive)
      components of galactose absorption were increased by 24 and 52% respectively
      during the chronic heat stress. 4. The size of the absorptive compartment may be
      reduced by the heat stress as reflected by decreased villus heights (19%) and wet
      (26%) and dry (31%) weights per unit length of jejunum. 5. It is suggested that
      the changes in hexose and amino acid during chronic exposure to elevated ambient
      temperature may reflect adaptations to optimise nutrient absorption in the face
      of reduced nutrition and decreases in the size of the absorptive compartment. A
      functional hypothyroidism (plasma luminal T3 decreased by 66%) associated with
      heat stress may contribute to the observed alterations in jejunal structure and
      function.

PMID- 1347723
TI  - Amino acids and serotonin in Limax maximum after a tryptophan devoid diet.
AB  - 1. Animals avoid diets lacking an essential amino acid, such as tryptophan (TRP),
      the precursor for serotonin (5-HT). 5-HT is important in the control of feeding.
      2. To study the effects of TRP deprivation, slugs were fed TRP-devoid (DEV) or
      control (COR) diets. 3. Food intake was depressed in DEV, as expected, but after
      2 weeks, the serontonergic metacerebral giant cell in DEV was still functional.
      4. Neither brain 5-HT nor plasma TRP concentration was affected. 5. Compared with
      food-restricted animals that had reductions in most amino acids, the DEV group
      sustained a marked plasma amino acid imbalance.

PMID- 1347724
TI  - Relationships between feeding, digestion and water balance in a carnivorous
      vertebrate, the toad Bufo bufo L.
AB  - 1. Toads fed meal worms retained water, amounting to about the mass of the meal.
      2. Secretion of gastric juice in the initial phase of digestion of a large meal
      would deplete the extracellular fluid of about half of the chloride ions. 3.
      Ingestion and rapid digestion of large meals in toads and other carnivorous
      vertebrates imply tolerance of large variations in anion composition and acidity
      of the extracellular fluid.

PMID- 1347725
TI  - Effect of early postnatal long-term fasting on the development of peptide
      hydrolysis in chicks.
AB  - 1. Early development of peptide hydrolysis in the digestive tract was
      investigated in experiments with fasted and fed ad lib. chicks during the first
      decade of postnatal period. 2. Pancreatic carboxypeptidase A (CPA) activity was
      maximal at the moment of hatch. On the second day CPA activity considerably
      diminished in starved and fed animal groups; further starvation (3-4 days) led to
      the significant increase of CPA total and specific activity, whereas the amount
      of enzyme in pancreas of fed chicks was rather low. 3. Aminopeptidase (AP)
      activity of the small intestinal surface was less sensitive to starvation. The
      increase of activity in all intestinal parts was observed only on the 4th day of
      fasting. The most sensitive to starvation were dipeptidases. Changes in their
      activity (2-fold increase) were detected after 24 hr of starvation. 4. The
      formation of specific physiological proximo-distal gradient of intestinal
      exopeptidase activities began only after the moment of the first feeding. 5. This
      gives evidence that the development of peptide hydrolysis depends not only on the
      age of the animal but also on the normal physiological beginning of the process
      of exogenous nutrition.

PMID- 1347726
TI  - Effect of gamma-linolenic acid on lipid metabolism in laying hens.
AB  - 1. Single comb white leghorn laying hens were given diets with additional mould,
      Mucus circineloides, containing gamma-linolenic acid (GLA) at levels of 0, 2.59
      and 5.06 g GLA/kg diet ad lib. for 2 weeks and serum lipid contents were
      determined in experiment 1. 2. Serum low density lipoprotein and chylomicron
      levels were significantly reduced with the increase of dietary GLA levels. Serum
      triglyceride and cholesterol tended to be lowered by dietary GLA, but not
      significantly different. 3. Effects of mould GLA and extracted oil GLA on the egg
      yolk cholesterol concentration and fatty acid composition were compared in
      experiment 2. Both mould GLA and extracted oil GLA diets containing 5.32 and 4.71
      g GLA/kg diet were given ad lib. for 2 weeks. 4. Yolk cholesterol content was not
      affected by dietary GLA sources. Content of GLA in the yolk was not altered,
      although that of arachidonic acid was enhanced by dietary GLA supplementation,
      particularly by the extracted oil GLA. 5. It is suggested that GLA is rapidly
      metabolized to arachidonic acid in the body and incorporated into the yolk.

PMID- 1347727
TI  - Lipid and tocopherol composition of farm-raised striped and hybrid striped bass.
AB  - 1. Hybrid striped bass (HB) were heavier and fatter than striped bass (SB) at
      harvest. 2. Total lipid, triacylglycerol and phospholipid fractions from muscle
      tissue of HB were characterized as having significantly larger quantities of
      polyunsaturated fatty acids than SB, while SB contained larger quantities of
      omega 3 fatty acids (specifically 22:6 and 20:5) than HB. 3. HB muscle tissue
      contained 14.99 and 11.42 micrograms/g dry weight of alpha- and gamma-tocopherol,
      respectively, while SB muscle tissue contained 38.77 and 7.15 micrograms/g dry
      weight of alpha- and gamma-tocopherol, respectively.

PMID- 1347728
TI  - Gastrin metabolism in neonatal pigs and grower-pigs.
AB  - 1. Half-life (1.7 +/- 0.1 min), distribution volume (146 +/- 12 ml/kg) and
      metabolic clearance rate (28 +/- 1 ml/kg/min) of little gastrin (G17) in neonatal
      pigs (N = 6; 3-12 days old) were significantly different from those in grower
      pigs (N = 4; 161-170 days old) (2.4 +/- 0.1 min; 58 +/- 2 ml/kg; 7.9 +/- 0.3
      ml/kg/min, respectively). 2. Half-life (33 +/- 4 min) and distribution volume
      (265 +/- 33 ml/kg) of big gastrin (G34) in neonatal pigs were greater but not
      significantly different from those in grower-pigs (24 +/- 2 min; 217 +/- 20
      ml/kg, respectively). 3. Half-life of G17 in liver extracts from pigs 2-90 days
      old (40.4 +/- 4.2 min) was significantly longer than in kidney extracts (22.0 +/-
      1.7 min). Half-lives of G34 in liver and kidney extracts from pigs 10-90 days old
      (78 +/- 6; 74 +/- 4 min, respectively) were significantly shorter than the
      corresponding values for 2-day-old pigs (134 +/- 3; 149 +/- 9 min, respectively).
      4. Since G34 is the major circulating form of gastrin in neonatal pigs the
      relative longer half-life of G34 to G17 in these animals may contribute to the
      higher circulating gastrin concentration compared with that in older animals.

PMID- 1347729
TI  - Oral absorption of biologically active insulin in common carp (Cyprinus carpio
      L.).
AB  - 1. Bovine insulin dissolved in 0.05 M deoxycholic acid was absorbed through oral
      intubation in fish weighing 200-300 g. 2. The peak of absorption appeared in all
      fish, 30-45 min after intubation and was followed by a gradual decrease. The
      extent of absorption was extremely variable, with up to a 20-fold difference
      between individuals. No detectable insulin was found in fish intubated with
      vehicle. 3. The absorbed hormone retained 17-88% of its lipogenic bioactivity in
      vitro. The absorbed insulin lowered the levels of several amino acids in the
      intubated fish, indirectly indicating that its bioactivity was also retained in
      vivo.

PMID- 1347730
TI  - An in vitro gas equilibration method for determination of chemical partition
      coefficients in fish.
AB  - 1. A gas equilibration method for the determination of in vitro chemical
      partition coefficients in mammals was adapted for use with fish. 2. In vitro
      blood: water and tissue: blood partition coefficients were determined for three
      chlorinated ethanes in rainbow trout (Oncorhynchus mykiss). 3. In vitro partition
      coefficients accurately predicted chemical concentrations in tissues of exposed
      trout.

PMID- 1347732
TI  - The primary culture of mouse adipocyte precursor cells in defined medium.
AB  - 1. A defined medium supporting the proliferation and differentiation of adipocyte
      precursors isolated from inguinal fat pads of 8-12-day-old mice was developed. 2.
      It consists of a 1:1 mixture of DME and WAJC404A media supplemented with insulin
      (10 micrograms/ml), transferrin (10 micrograms/ml), fibroblast growth factor (10
      ng/ml) and high density lipoproteins (HDL) (90 micrograms protein/ml). 3. DME-F12
      medium (1:1 mixture) used as a nutrient mixture in the defined medium of rat and
      human adipocyte precursors was inadequate for cultivating mouse adipocyte
      precursors. 4. HDL had a definite beneficial effect on both preadipocyte growth
      and differentiation. 5. Differentiation was enhanced by addition of dexamethasone
      (10(-9) M) but could be almost completely inhibited by transforming growth factor
      beta 1 (TGF-beta 1). 6. TGF-beta 1 was shown to be effective only when present in
      the early stages of differentiation.

PMID- 1347731
TI  - Uptake of uric acid and p-aminohippurate (PAH) by renal cortical slices of
      various mammals.
AB  - 1. Accumulation of uric acid and PAH was measured in renal cortical slices of
      various mammalian species. 2. The slice to medium ratio of uric acid was above
      unity in the rabbit, guinea pig, pig and cow, suggesting an active accumulation
      of uric acid, while it was near or below unity in the rat and mongrel dog. 3.
      Uric acid uptake in the rabbit, guinea pig and cow was significantly inhibited by
      PAH. 4. Uric acid was a potent inhibitor of PAH uptake in the rabbit, guinea pig,
      dog and pig, but much less potent in the rat and cow. 5. Kinetic analysis showed
      that uric acid inhibited PAH uptake in a competitive manner in all species
      studied except for the cow showing a noncompetitive type. 6. These results
      indicate that uric acid and PAH share a common transport mechanism at the
      basolateral membrane of the rabbit, guinea pig and pig.

PMID- 1347733
TI  - Stabilization of the adenylate energy charge in erythrocytes of rats and humans
      at high altitude hypoxia.
AB  - 1. Stabilization of adenylate energy charge and control of adenylate pool were
      analysed in the erythrocytes of the rat and the human exposed to highly hypoxic
      conditions. 2. Red cell energy charge was decreased in the rats exposed to a
      simulated altitude of 5000-8000 m, and then recovered to the normal value with
      the depletion of adenylate pool. 3. The energy charge and the adenylate pool size
      of the human erythrocytes did not show any change under highly hypoxic
      conditions. 4. Anaerobic incubation of rat erythrocytes caused a marked decrease
      in the energy charge, and its recovery was accompanied by the depletion of total
      adenylates. 5. The energy charge and total adenylates of human red cells did not
      change under the anaerobic incubation of erythrocytes. 6. These results suggest
      that the energy charge of rat erythrocytes can be controlled by depletion of the
      adenylate pool, but the adenylate degradation is not responsible for the
      stabilization of the energy charge in human erythrocytes.

PMID- 1347734
TI  - Evidence for angiotensin-like molecules in the central nervous system of the
      leech Theromyzon tessulatum (O.F.M.). A possible diuretic effect.
AB  - 1. Cells in the central nervous system of the leech Theromyzon tessulatum were
      revealed with an antiserum against angiotensin II. Among these cells, a group of
      4-5 pairs of neurons, called beta giant cells, and located in the posterior
      compartments of the supraesophageal ganglion was particularly investigated. 2.
      The amount of angiotensin II-like substance(s) in the brain increased notably in
      the days immediately following the third meal. 3. Injections of angiotensin II,
      fragments 1-4 or 5-8 or angiotensin II and of angiotensin III into stage 3
      leeches showed that fragment 5-8 of angiotensin II was the most effective: it
      provokes a loss of mass of the leeches, which could express a diuretic effect.

PMID- 1347735
TI  - Dendritic and sustained shifts in potential to electrical stimulation of the
      anuran tectal surface.
AB  - 1. Recordings of dendritic potentials and sustained potential shifts (SPS) were
      made from the brain of immobilised frogs during surface tectal electrical
      stimulation. 2. Single pulses evoked dendritic responses; trains caused decay of
      dendritic responses on the background of the evoked SPS. 3. The tectal surface
      SPS declined with distance from the stimulating electrode. 4. The negative
      surface SPS declined with tectal depth to ca 300 microns, then reversed polarity
      and increased in amplitude with depth up to 700 microns.

PMID- 1347736
TI  - Taste synergism between monosodium glutamate and 5'-ribonucleotide in mice.
AB  - 1. Strain differences of mice were found in the taste synergism between
      monosodium L-glutamate (MSG) and disodium 5'-guanylate (GMP). 2. Magnitudes of
      chorda tympani responses to the mixture of MSG and GMP over the sum of responses
      to each component were greater in the order of C3H/HeSlc(C3H) greater than
      C57BL/6CrSlc(C57BL) greater than BALB/cCrSlc(BALB) mice. The greatest synergism
      was observed in response to the mixture of 0.03 M MSG and 0.1 mM GMP, to which
      responses were about 2.6, 1.8 and 1.4 times greater than the sum of each
      component in C3H, C57BL and BALB mice, respectively. 3. Magnitudes of inhibition
      of MSG and mixture responses by the lingual treatment of proteolytic enzyme,
      Pronase E, were greater in the same order of C3H greater than C57BL greater than
      BALB mice as that observed in magnitudes of the synergism. These results suggest
      that there exists quantitative differences in receptors responsible for taste
      synergism between MSG and GMP among three mouse strains.

PMID- 1347737
TI  - [Long-term therapy and timing of surgical intervention in ulcerative colitis and
      Crohn disease].

PMID- 1347738
TI  - Hypothalamic preprosomatostatin messenger ribonucleic acid expression in mice
      transgenic for excess or deficient endogenous growth hormone.
AB  - The influence of altered endogenous GH status on somatostatin (somatotropin
      release-inhibiting hormone; SRIF) gene expression was studied in two transgenic
      mouse models. Transgenic dwarf mice carried the rat GH gene promoter fused to the
      diphtheria toxin A-chain gene, placing toxin expression under GH promoter
      control. As a result, the toxic product of the transgene ablated all GH
      expressing cells, resulting in undetectable circulating GH, reduced weight (10.6
      +/- 1.0 g for transgenic dwarfs vs. 29.5 +/- 1.7 g for controls; P less than
      0.001), and no detectable somatotrophs. Transgenic giant mice contained a
      construction combining a widely expressed metallothionein promoter and the human
      GH-releasing hormone (hGHRF) structural gene. Transgene expression of hGHRF
      resulted in overproduction of endogenous mouse GH in the anterior pituitary and
      weight increases (42.7 +/- 2.7 g for giants vs. 29.5 +/- 1.7 g for controls; P
      less than 0.005). Using in situ hybridization, control mice, transgenic dwarfs,
      and transgenic giants were compared for levels of prepro-SRIF mRNA. Hybridization
      signal intensities for prepro-SRIF mRNA were similar in transgenic dwarfs to
      those in littermate nontransgenic mice in non-GH-regulating regions of the brain,
      such as cortex (control, 31 +/- 2 U; dwarf, 27 +/- 2) and reticulothalamic
      nucleus (control, 41 +/- 2 U; dwarfs, 39 +/- 3). Transgenic giant mice had
      hybridization intensity of SRIF mRNA similar to that of normals in cortex
      (controls, 31 +/- 2 U; giant, 27 +/- 1) and reticulothalamic nucleus (controls,
      41 +/- 2 U; giant, 40 +/- 4). In the GH-regulating neurons of the anterior
      periventricular hypothalamus (PeN), prepro-SRIF mRNA signal in transgenic dwarf
      mice decreased to 60% of that in controls (88 +/- 13 U for dwarfs vs. 147 +/- 17
      U for controls; P less than 0.01), although the numbers of mRNA-expressing cells
      in the PeN were not different between the transgenic dwarfs and controls (dwarfs,
      69 +/- 6 cells; controls, 72 +/- 4 cells). The transgenic giant mice had 230%
      higher prepro-SRIF mRNA signal than control mice in the PeN (343 +/- 30 U in
      giants vs. 147 +/- 17 U in controls; P less than 0.001). Again, the numbers of
      mRNA-expressing cells were not different in giants (57 +/- 9) and normals (72 +/-
      4). These results suggest that while the lack of endogenous GH is accompanied by
      a slight decrease in transcriptional expression of SRIF in the PeN, the
      overproduction of endogenous GH greatly stimulates hypothalamic SRIF steady state
      mRNA levels.

PMID- 1347739
TI  - Time-dependent reduction and potentiation of growth hormone (GH) responsiveness
      to GH-releasing factor induced by exogenous GH: role for somatostatin.
AB  - Exogenous GH is known to exert a negative feedback effect on its own
      responsiveness to GH-releasing factor (GRF); however, the mechanism is not known.
      In the present study we examined the time course of effects of a single sc
      administration of recombinant human (rh) GH on GH responsiveness to GRF and
      investigated the possible involvement of somatostatin (SRIF) in this response.
      Free-moving adult male rats were administered 200 micrograms rhGH, sc, at 0800 h
      and subsequently challenged with 1 microgram GRF-(1-29)NH2, iv, at times of
      spontaneous peaks (1100 and 1500 h) and troughs (1300 h) in GH secretion during a
      6-h (1000-1600 h) sampling period. H2O-injected control rats exhibited the
      typical cyclic responsiveness to GRF stimulation, with GRF-induced GH release
      significantly greater during peak compared to trough periods of the GH rhythm.
      Pretreatment with rhGH 3 h before GRF injection markedly inhibited the GH
      response to GRF at a peak time [integrated GH release over 30 min, 1135 +/- 271
      vs. 6372 +/- 1185 ng/ml.30 min in H2O-injected controls (mean +/- SE); P less
      than 0.01]. In striking contrast, 5 h after rhGH administration, there was a 6
      fold augmentation of GH responsiveness to GRF compared to that in H2O-injected
      controls at a trough time (7032 +/- 1622 vs. 1128 +/- 216 ng/ml.30 min; P less
      than 0.01). High GH responsiveness to GRF was preserved 7 h after rhGH injection.
      Passive immunization of rhGH-treated rats with SRIF antiserum reversed the rhGH
      induced blunted GH response at 3 h (7985 +/- 366 vs. 1705 +/- 431 ng/ml.30 min in
      rhGH-treated control rats given normal sheep serum; P less than 0.01) and
      completely restored GH responsiveness to levels as high as those in H2O-injected
      controls. These results demonstrate that 1) a single sc injection of rhGH
      markedly attenuates GH responsiveness to GRF acutely for about 3 h, but
      subsequently enhances somatotroph sensitivity to the stimulatory actions of GRF;
      and 2) the short term blunting of GRF-induced GH release by rhGH is due at least
      in part to increased release of endogenous SRIF. The subsequent potentiation of
      GH responsiveness to GRF is probably due to a SRIF-mediated build-up of pituitary
      GH stores in a readily releasable pool. Such a mechanism of GH autofeedback may
      play a physiological role in the genesis of pulsatile GH secretion.

PMID- 1347740
TI  - Modulation of glucocorticoid induction of tyrosine aminotransferase gene
      expression by variations in cell density.
AB  - Glucocorticoids induce tyrosine aminotransferase (TAT) in hepatoma cells. We have
      previously shown that both the concentration of the agonist dexamethasone (Dex)
      required for half-maximal induction (EC50) and the amount of agonist activity
      produced by the antagonist dexamethasone 21-mesylate (Dex-Mes), expressed as a
      percentage of maximum induction achieved by Dex, are different in Fu5-5 and HTC
      cells. Furthermore, both activities vary over several weeks in each cell line in
      an apparently random manner, but, nevertheless, are correlated by a linear
      semilog plot. We now find that this long term and previously unpredictable
      variation in both the Dex EC50 and the amount of Dex-Mes agonist activity for the
      induction of TAT enzyme activity can be made to occur reproducibly in 40 h or
      less by changing the cell density and/or amount of medium in the tissue culture
      plates. Thus, a higher cell density and/or a lower volume of medium produced both
      higher amounts of Dex-Mes agonist activity and lower EC50 values for Dex.
      Experiments with cells at different densities but exposed to the same medium
      indicated that cell density was the dominant determinant. A qualitatively
      identical modulation was seen at the level of TAT mRNA, but not mouse mammary
      tumor virus RNA. We are not aware of any previous report of cell growth
      conditions altering either the level of agonist activity of an antisteroid or the
      EC50 of a full agonist. These results further indicate that extrachromosomal
      parameters, such as cell-cell contact and/or a diffusable factor(s), can modulate
      the basic features of glucocorticoid induction of some, but not all,
      glucocorticoid-inducible genes.

PMID- 1347741
TI  - Autonomic nervous system mediation of the pancreatic polypeptide response to
      insulin-induced hypoglycemia in conscious rats.
AB  - To investigate the neural regulation of pancreatic polypeptide (PP) secretion
      during hypoglycemia in the rat, insulin was administered to chronically
      cannulated rats, and plasma PP responses were compared between saline-treated
      animals and animals pretreated with a ganglionic blocking agent (hexamethonium),
      a muscarinic antagonist (atropine), combined alpha- and beta-adrenergic receptor
      blockade (propranolol + tolazoline), or combined adrenergic blockade + atropine.
      PP was measured using a new RIA which selectively detects PP in rat plasma. In
      control rats (n = 10), plasma PP increased from a baseline level of 30 +/- 3
      pg/ml to 271 +/- 41 pg/ml during hypoglycemia (plasma glucose = 29 +/- 2 mg/dl)
      (delta PP = +241 +/- 42 pg/ml, P less than 0.0005), demonstrating that in rats,
      as in other species, insulin-induced hypoglycemia is a potent stimulus for PP
      release. PP only increased by 31 +/- 10 pg/ml during similar hypoglycemia in 7
      hexamethonium-treated rats (P less than 0.01 vs. control animals). Thus, at least
      90% of the PP response to hypoglycemia is neurally mediated. The plasma PP
      response to hypoglycemia was +85 +/- 24 pg/ml in atropine-treated rats (P 0.01
      vs. control rats), suggesting that approximately 65% of the PP response is
      mediated via muscarinic acetylcholine receptors on the islet F cell. The PP
      response to hypoglycemia in rats with combined adrenergic blockade (delta = +168
      +/- 32 pg/ml) was slightly, but not significantly smaller than that in control
      rats. The combination of combined blockade + atropine resulted in a PP response
      (delta = +26 +/- 7 pg/ml) to hypoglycemia that was similar to that in
      hexamethonium-treated rats (P less than 0.01 vs. control rats). These results
      suggest: 1) The PP response to hypoglycemia is predominantly the result of
      muscarinic, cholinergic activation. 2) There is a minor adrenergic contribution
      to the response. 3) The plasma PP response may be useful as an index of autonomic
      neural input to the islet during hypoglycemia.

PMID- 1347742
TI  - Regulation of intermediate pituitary corticotropin-releasing hormone receptors by
      dopamine.
AB  - It has been shown that chronic cold exposure results in selective CRH receptor up
      regulation in the intermediate pituitary. Since the intermediate pituitary is
      under dopaminergic control, the participation of a dopaminergic mechanism in the
      effect of cold stress was studied in rats treated with dopaminergic agonists and
      antagonists. CRH receptors were measured by the binding of radioiodinated Tyr
      ovine (o) CRH to neurointermediate pituitary membranes of slide-mounted sections.
      Cold exposure for 60 h caused the expected increase in CRH binding in
      neurointermediate lobe membranes. Administration of the dopaminergic agonist
      bromocriptine did not prevent the effect of cold stress, but increased CRH
      binding in control rats. The dopaminergic antagonist metoclopramide decreased
      intermediate pituitary CRH binding in control and cold-exposed rats.
      Bromocriptine administration for 1-8 days caused a progressive increase in the
      binding of [125I]Tyr-oCRH in neurointermediate pituitary membranes, despite
      atrophy of the intermediate zone. Scatchard analysis of the binding data
      indicated that the changes were due to variations in receptor concentration,
      without changes in affinity. No changes in anterior pituitary CRH receptors were
      observed with agonist or antagonist treatment. Autoradiographic analysis of CRH
      binding after 3 days of treatment with bromocriptine or haloperidol confirmed the
      results observed in membranes and demonstrated that changes in binding were
      confined to the intermediate lobe. The functional consequences of the changes in
      CRH binding were studied by analysis of adenylate cyclase activity in cells and
      homogenates of intermediate pituitaries of rats treated with bromocriptine. In 18
      h cultured intermediate pituitary cells from rats treated with bromocriptine for
      3 days, CRH-stimulated cAMP production, measured in the presence of
      phosphodiesterase inhibitors, was increased to levels only slightly higher than
      those in cells from control rats. Likewise, CRH-stimulated adenylate cyclase,
      measured by conversion of [32P]ATP to [32P] cAMP, was not significantly different
      in homogenates from microdissected intermediate lobes from control and
      bromocriptine-treated rats. The lack of parallel changes in adenylate cyclase
      responsiveness suggests only partial receptor coupling, probably reflecting an
      inhibitory effect of dopamine on components of the adenylate cyclase. This study
      demonstrates that in contrast to the recognized inhibitory effect on cell
      division and POMC mRNA expression, dopamine causes up-regulation of CRH receptors
      in the intermediate pituitary. The qualitatively similar and nonadditive effects
      of cold stress and dopaminergic agonists suggest that a dopaminergic mechanism
      may be involved in intermediate pituitary CRH receptor regulation during chronic
      cold stress.

PMID- 1347743
TI  - Aging enhances inhibitory action of somatostatin in rat pancreas.
AB  - This study examines the effects of donor age on exogenous somatostatin inhibition
      of insulin secretion stimulated by 10 mM D-glyceraldehyde and by 20 mM beta-D
      glucose in isolated perfused rat pancreas. Both 6 and 30 nM synthetic
      somatostatin-14 affect both glyceraldehyde- and glucose-stimulated insulin
      secretion to a greater degree in pancreases from old animals (24-27 months) than
      in those from young (2-5 months). We conclude that an increased sensitivity to
      inhibitory actions of somatostatin during aging, observed in pituitary tissues in
      vitro, occurs in pancreatic tissues as well and may constitute a general
      phenomenon in tissues subject to somatostatin inhibition.

PMID- 1347744
TI  - A transferable silencing domain is present in the thyroid hormone receptor, in
      the v-erbA oncogene product and in the retinoic acid receptor.
AB  - Inhibition of gene transcription is brought about by several mechanisms. The
      least understood mechanism is probably silencing, the analogue to transcriptional
      enhancing. We provide evidence that the silencing function of the oncogene
      product v-ERBA or the cellular counterpart, the thyroid hormone receptor (TR, c
      erbA) is located in the C-terminal part and is transferable to a heterologous DNA
      binding domain. Deletion analyses suggest an important role for a basic and
      hydrophilic amino acid stretch on both ends of the domain. In addition we show
      that the related retinoic acid receptor (RAR) also contains a functional
      silencing domain similar in size and amino acid sequence. However, the activity
      of this domain can be neutralized by an additional domain in the C-terminus which
      functions cell specifically.

PMID- 1347747
TI  - Cell surface marker analysis of mouse thymic dendritic cells.
AB  - Cell surface markers of mouse thymic dendritic cells have been studied by flow
      cytometry after isolation by collagenase digestion, separation of the low-density
      cell fraction and differential adherence. The dendritic cell preparation had a
      purity of greater than 90%, the contaminating population being essentially
      composed of thymocytes, macrophages constituting less than 1%. Dendritic cells
      displayed high forward and low-intermediate side angle scatter, and expressed
      high levels of major histocompatibility complex (MHC) class I and class II
      molecules, the heat-stable antigen (HSA), the adhesion molecules Pgp-1 (CD44),
      LFA-1, ICAM-1 and low levels of Mac-1 and the leukocyte common antigen CD45.
      Thymic dendritic cells are negative for the stem cell antigen-2 (Sca-2), the B
      cell-specific form of CD45 (B220), the mouse macrophage markers Fc receptor and
      F4/80, and the granulocyte marker Gr-1. However, although they do not express the
      T cell markers Thy-1, CD2, CD3, CD4 and CD5, 20%-30% of dendritic cells are
      positive for the interleukin 2 receptor alpha chain (CD25), and about 30% express
      intermediate levels of CD8. These results are discussed with regard to the
      functional significance of the expression of CD8 by thymic dendritic cells, and
      the existence of different dendritic cell subpopulations in the murine thymus.

PMID- 1347745
TI  - A subdomain in the transmembrane domain is necessary for p185neu* activation.
AB  - The neu proto-oncogene encodes a protein highly homologous to the epidermal
      growth factor receptor. The neu protein (p185) has a molecular weight of 185,000
      Daltons and, like the EGF receptor, possesses tyrosine kinase activity. neu is
      activated in chemically induced rat neuro/glioblastomas by substitution of valine
      664 with glutamic acid within the transmembrane domain. The activated neu*
      protein (p185*) has an elevated tyrosine kinase activity and a higher propensity
      to dimerize, but the mechanism of this activation is still unknown. We have used
      site-directed mutagenesis to explore the role of specific amino acids within the
      transmembrane domain in this activation. We found that the lateral position and
      rotational orientation of the glutamic acid in the transmembrane domain does not
      correlate with transformation. However, the primary structure in the vicinity of
      Glu664 plays a significant role in this activation. Our results suggest that the
      Glu664 activation involves highly specific interactions in the transmembrane
      domain of p185.

PMID- 1347748
TI  - The human intraepithelial lymphocyte marker HML-1 is an integrin consisting of a
      beta 7 subunit associated with a distinctive alpha chain.

PMID- 1347746
TI  - Antp-type homeodomains have distinct DNA binding specificities that correlate
      with their different regulatory functions in embryos.
AB  - Much of the functional specificity of Drosophila homeotic selector proteins, in
      their ability to regulate specific genes and to assign specific segmental
      identities, appears to map within their different, but closely related
      homeodomains. For example, the Drosophila Dfd and human HOX4B (Hox 4.2) proteins,
      which have extensive structural similarity only in their respective homeodomains,
      both specifically activate the Dfd promoter. In contrast, a chimeric Dfd protein
      containing the Ubx homeodomain (Dfd/Ubx) specifically activates the Antp P1
      promoter, which is normally targeted by Ubx. Using a variety of DNA binding
      assays, we find significant differences in DNA binding preferences between the
      Dfd, Dfd/Ubx and Ubx proteins when Dfd and Antp upstream regulatory sequences are
      used as binding substrates. No significant differences in DNA binding specificity
      were detected between the human HOX4B (Hox 4.2) and Drosophila Dfd proteins. All
      of these full-length proteins bound as monomers to high affinity DNA binding
      sites, and interference assays indicate that they interact with DNA in a way that
      is very similar to homeodomain polypeptides. These experiments indicate that the
      ninth amino acid of the recognition helix of the homeodomain, which is glutamine
      in all four of these Antp-type homeodomain proteins, is not sufficient to
      determine their DNA binding specificities. The good correlation between the in
      vitro DNA binding preferences of these four Antp-type homeodomain proteins and
      their ability to specifically regulate a Dfd enhancer element in the embryo,
      suggests that the modest binding differences that distinguish them make an
      important contribution to their unique regulatory specificities.

PMID- 1347749
TI  - Overexpression of multidrug resistance-associated p170-glycoprotein in acute non
      lymphocytic leukemia.
AB  - Resistance to several cytotoxic agents, including anthracyclines, vinca alkaloids
      and epipodophylline derivatives (multidrug resistance, or MDR) can develop in
      tumor cells by overexpression of a 170-kd glycoprotein (p170) which is an
      essential component of a membrane transport system leading to increased drug
      efflux and decreased intracellular drug concentration. By means of a p170
      directed monoclonal antibody (MRK-16) and immunocytochemistry (alkaline
      phosphatase anti-alkaline phosphatase technique), we investigated the expression
      of p170 in marrow blast cells of 59 cases (38 at diagnosis and 21 in relapse) of
      acute-non-lymphocytic leukemia (ANLL). The proportion of strongly MDR-positive
      cells was higher in relapse that at diagnosis (median 15.5% vs 1.5%). Out of 31
      patients who were evaluable for the results of first remission induction, failure
      of first-line treatment (including Daunorubicin, standard-dose and high-dose
      Arabinosyl Cytosine, and sometimes also Mitoxantrone) occurred in 8/22 MDR
      positive cases and in 1/9 MDR-negative ones (p = 0.21). Failure of first-line
      treatment was always associated with a progressive increase of p170 expression.
      Total failures (no remission plus early relapse) were more frequent (p = 0.001)
      among MDR-positive cases (16/22) than among the others (2/9). These data show
      that MDR is very frequent in ANLL also at diagnosis and suggest that MDR can
      contribute to early failure of standard treatment.

PMID- 1347750
TI  - The LIM domain-containing homeo box gene Xlim-1 is expressed specifically in the
      organizer region of Xenopus gastrula embryos.
AB  - A novel cysteine-rich motif, named LIM, has been identified in the homeo box
      genes lin-11, Isl-1, and mec-3; the mec-3 and lin-11 genes determine cell
      lineages in Caenorhabditis elegans. We isolated LIM class homeo box genes from
      Xenopus laevis that are closely related to lin-11 and mec-3 in the LIM and homeo
      domains. This paper deals with one of these genes, Xlim-1. Xlim-1 mRNA is found
      at low abundance in the unfertilized egg, has a major expression phase at the
      gastrula stage, decreases, and rises again during the tadpole stage. In adult
      tissues the brain shows the highest abundance, by far, of Xlim-1 mRNA. The
      maternal and late expression phases of the Xlim-1 gene suggest that it has
      multiple functions at different stages of the Xenopus life cycle. In the gastrula
      embryo, Xlim-1 mRNA is localized in the dorsal lip and the dorsal mesoderm, that
      is, in the region of Spemann's organizer. Explant experiments showed that Xlim-1
      mRNA is induced by the mesoderm-inducer activin A and by retinoic acid, which is
      not a mesoderm inducer but affects patterning during Xenopus embryogenesis;
      application of activin A and retinoic acid together results in synergistic
      induction. The structure, inducibility, and localized expression in the organizer
      of the Xlim-1 gene suggest that it has a role in establishing body pattern during
      gastrulation.

PMID- 1347751
TI  - Inhibitory effects of nicotinamide on recombinant human interferon-gamma-induced
      intercellular adhesion molecule-1 (ICAM-1) and HLA-DR antigen expression on
      cultured human endothelial cells.
AB  - Intercellular adhesion molecule-1 (ICAM-1), HLA-A, B, C and HLA-DR antigen on
      endothelial cells (EC) play important roles in the development of inflammatory
      processes in autoimmune disorders. In the present study, we investigated the
      effect of nicotinamide, an inhibitor of poly(ADP ribose) synthetase, on
      interferon-gamma (IFN gamma)-induced ICAM-1 and HLA-DR antigen expression on the
      surface of cultured human umbilical vein endothelial cells, assessed by flow
      cytometry, and EC proliferation by counting cell numbers and [3H]thymidine
      incorporation assays. Nicotinamide dose-dependently inhibited the IFN-gamma
      induced ICAM-1 and HLA-DR antigen expression, but not HLA-A, B, C antigen
      expression on cultured EC. Furthermore, nicotinamide significantly inhibited
      endothelial cell proliferation, as assessed by [3H]thymidine incorporation assay.
      Our findings suggest that nicotinamide may suppress mononuclear cell
      infiltration, antigen presentation and angiogenesis in the lesions of autoimmune
      disorders by reducing both IFN gamma-induced ICAM-1 and HLA-DR antigen expression
      on EC, and EC proliferation. Therefore, nicotinamide can be used for the
      treatment and prevention of the development of autoimmune disorders.

PMID- 1347752
TI  - Flow cytometric analysis of the expression of murine B and T surface markers from
      birth to adulthood.
AB  - The proportion of nucleated splenocytes bearing B-lymphocyte markers B220,
      surface IgM (sIgM) and sIgD, as well as the T-lymphocyte markers Thy 1.2, CD5,
      CD8a and CD4 were quantitated by flow cytometric analysis (FACS) throughout
      postpartum development in the A/J mouse. Full expression of B lymphocyte markers
      was achieved much sooner than expression of T lymphocyte markers. This was
      especially true for B220, which was found on 8% of all splenocytes at day 5 and
      reached adult levels (47-50%) by weaning at day 22. Expression of sIgM and sIgD
      were 13% and 9%, respectively, of all splenocytes at day 5 with mature levels not
      expressed until day 35 postpartum (approximately 36% of cells were positive for
      these markers). T lymphocyte markers, on the other hand, did not reach full
      expression until sexual maturity. For example, Thy 1.2 expression was 8% on day 5
      and did not reach mature levels (28-30%) until day 56. CD5 closely paralleled Thy
      1.2 expression rising from only 2% on day 5 to 27% by day 56. Likewise, CD8a and
      CD4 marker development paralleled one another with CD8a rising from 1% on day 5
      to 10% by day 56 and CD4 rising from 5% on day 5 to 19% by day 56. These data
      demonstrate the variability in the time of appearance and rate of maturation of
      the various lymphocyte cell surface markers during postpartum development. They
      also serve as a reference to identify alterations in lymphocyte development
      created by immunodeficiency diseases.

PMID- 1347753
TI  - Application of anti-CD3-treated lymphocytes as stimulator cells in human
      autologous mixed lymphocyte cultures for generation of autorestricted CD8+
      suppressor T cells.
AB  - The purpose of the present study was to investigate the application of anti-CD3
      treated lymphocytes as stimulator cells in human one-way autologous mixed
      lymphocyte cultures (MLC) for the generation of suppressor cells. MLC-activated
      CD4-CD8+ CD16- T cells were non-cytotoxic, while they down-regulated the
      proliferation of autologous (but not allogeneic) responder lymphocytes in
      allogeneic test MLC.

PMID- 1347754
TI  - T cell receptor gamma/delta expression on lymphocyte populations of breast cancer
      patients.
AB  - The quantitative distribution and phenotype of gamma/delta lymphocytes in the
      peripheral blood (PBL), tumour draining lymph node (LNL) and tumour infiltrating
      lymphocytes (TIL) from breast carcinoma patients were determined by one- and two
      colour flow cytometry. The TCR-gamma/delta + cells generally expressed the T cell
      lineage antigen CD3. The proportions of such cells were variable but generally
      small from all the three sources. Phenotypic analysis revealed that the CD8
      marker was consistently and predominantly observed on gamma/delta + CD3+ cells in
      the tumour infiltrate, whereas CD4 expression, while generally low, was noted on
      a significant percentage (median 10%) of LNL gamma/delta + lymphocytes. In both
      PBL and LNL the predominant gamma/delta cell population was CD4-8-.

PMID- 1347755
TI  - The bactericidal capacity of peripheral blood monocytes from HIV positive
      patients may collapse very soon after the infection.
AB  - The activity of peripheral blood monocytes from HIV positive patients was
      measured by the intensity of the chemoluminescence those cells emit when they
      ingest a foreign particle. In most patients (84%) that value was impaired. Such
      an alteration may occur very early in the course of the disease. The anti-p24
      antibody titer was correlated with monocyte phagocytic potential as measured by
      the chemoluminescent value thus indicating the need for adequate monocyte
      activity in order to obtain antibody formation. The severity of opportunistic
      infections that HIV positive subjects may develop is a clear indication that
      their immune systems are abnormal. The most frequently affected cells are those
      which bear the viral receptor, the CD4 antigen. Those cells are mainly the helper
      T cells and monocytes. The monocytes are the immune system phagocytic cells which
      actively control infections, in part by the release oxidative radicals. Those
      radicals can easily be measured by the chemoluminescence (CL) the cells emit when
      they ingest a foreign particle. This study examines the CL emitted by peripheral
      blood monocytes from HIV-positive and control subjects while they phagocytose
      opsonized zymosan in vitro and correlates these values with other laboratory
      parameters.

PMID- 1347756
TI  - Transitory expression of Thy-1 antigen in immature B cell lines.
AB  - In cmu- B220+ Thy-1- murine immature B cells transformed with a temperature
      sensitive mutant of Abelson murine leukemia virus, a low level of Thy-1 antigen
      was transitorily expressed after the shift of the culture temperature from the
      permissive (35 degrees C) to the non-permissive (39 degrees C) temperature. On
      the other hand, B220 antigen was persistently expressed regardless of whether the
      cells were cultured at the permissive or non-permissive temperature. No other T
      lineage-specific antigens, CD3, CD4, and CD8 were induced during the culture at
      the non-permissive temperature. Expression of Thy-1 antigen was confirmed by the
      detection of a low level of Thy-1-specific mRNA. These results clearly showed
      that immature B cells could express Thy-1 antigen during proliferation and/or
      differentiation. The results imply a role for Thy-1 antigen in B cell
      proliferation and/or differentiation.

PMID- 1347757
TI  - Lovastatin and coadministered antihypertensive/cardiovascular agents.
AB  - Hypertension and hypercholesterolemia frequently coexist and may require
      concomitant drug treatments. The efficacy and safety profile of lovastatin given
      in the presence of antihypertensive medication was evaluated using patient
      subgroups identified in the Expanded Clinical Evaluation of Lovastatin (EXCEL)
      Study. The EXCEL study examined 8,245 patients with moderate hypercholesterolemia
      randomly assigned either to a group treated with lovastatin (20-80 mg daily) or
      to a group given placebo for 48 weeks. After adjustment for patient
      characteristics, pairwise comparisons were made between patients taking no
      antihypertensive agents (n = 3,772) and those taking either calcium antagonists
      (n = 446), selective beta 1-adrenergic receptor blockers (n = 326), nonselective
      beta-adrenergic receptor blockers (n = 219), potassium-sparing diuretics (n =
      187), thiazide diuretics (n = 126), or angiotensin converting enzyme inhibitors
      (n = 171). The placebo-corrected dose-dependent effect of lovastatin on the
      percent change from baseline in low-density lipoprotein cholesterol was not
      attenuated in any subgroup and was slightly enhanced in the calcium antagonist
      subgroup (-29% to -44%, p = 0.06) when compared with patients taking no
      antihypertensive agents (-24% to -40%); this difference, however, was only of
      borderline significance. Patterns of lovastatin-induced increase in high-density
      lipoprotein cholesterol and decrease in triglycerides were not consistently
      different among the subgroups. Examination of mean changes in serum
      transaminases, mean changes in creatine kinase, and the proportion of patients
      discontinuing therapy for clinical adverse experiences did not indicate the
      presence of an interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347758
TI  - Susceptibility of porcine intestine to pilus-mediated adhesion by some isolates
      of piliated enterotoxigenic Escherichia coli increases with age.
AB  - Two porcine isolates of enterotoxigenic Escherichia coli (ETEC) (serogroup O157
      and O141) derived from fatal cases of postweaning diarrhea and lacking K88, K99,
      F41, and 987P pili (4P- ETEC) were tested for adhesiveness to small-intestinal
      epithelia of pigs of different ages. Neither strain adhered to isolated
      intestinal brush borders of newborn (1-day-old) pigs in the presence of mannose.
      However, mannose-resistant adhesion occurred when brush borders from 10-day- and
      3- and 6-week-old pigs were used. Electron microscopy revealed that both strains
      produced fine (3.5-nm) and type 1 pili at 37 degrees C but only type 1 pili at 18
      degrees C. Mannose-resistant in vitro adhesion to brush borders of older pigs
      correlated with the presence of fine pili. These strains produced predominantly
      fine pili in ligated intestinal loops of both older and newborn pigs, but
      adherence was greater in loops in older pigs. Immunoelectron microscopic studies,
      using antiserum raised against piliated bacteria and absorbed with nonpiliated
      bacteria, of samples from brush border adherence studies revealed labelled
      appendages between adherent bacteria and intestinal microvilli. Orogastric
      inoculation of pigs weaned at 10 and 21 days of age indicated significantly (P
      less than 0.001) higher levels of adhesion by the ETEC to the ileal epithelia of
      older pigs than to that of younger ones. We suggest that small-intestinal
      adhesion and colonization by these ETEC isolates is dependent on receptors that
      develop progressively with age during the first 3 weeks after birth. Furthermore,
      our data are consistent with the hypothesis that the fine pili described mediate
      intestinal adhesion by the 4P- ETEC strains studied.

PMID- 1347759
TI  - Interleukin-6 response of epithelial cell lines to bacterial stimulation in
      vitro.
AB  - This study demonstrated that epithelial cell lines secrete interleukin-6 (IL-6)
      in response to stimulation with gram-negative bacteria. Human epithelial cell
      lines of urinary tract origin (A-498 and J82) and of intestinal origin (HT-29 and
      Caco-2) were analyzed for the secretion of IL-6 by using the B9 bioassay. The
      supernatants from cells maintained with culture medium were used to assess the
      constitutive production of IL-6. The supernatants from cells exposed to
      Escherichia coli strains, lipopolysaccharide, lipid A, and isolated fimbriae were
      used to quantitate the IL-6 response to these stimulants. The urinary tract
      epithelial cell lines were found to constitutively secrete IL-6. The IL-6
      activity in the supernatants of the bladder cell line (J82) increased above
      constitutive levels after 2 h of stimulation by most of the bacterial strains
      tested. The IL-6 activity in the supernatants of the kidney line (A-498)
      accumulated at a constant rate over the 24-h assay period. The role of bacterial
      adherence for the induction of IL-6 production was investigated by comparing the
      responses to recombinant E. coli strains expressing different fimbriae. In
      addition, isolated P and S fimbriae with and without the receptor binding domain
      were also used as stimulants. The IL-6 activity in the supernatants of the
      bladder cell line increased after exposure to bacteria and bacterial products
      regardless of their adhesive properties. In contrast, the kidney cell line was
      stimulated to secrete significantly more IL-6 by adhering bacteria and by adhesin
      positive P fimbriae than by nonadhering bacteria or adhesin-negative P fimbriae.
      The S-fimbrial preparations had no specific effects on the IL-6 activity of the
      cell supernatants. These results are consistent with our hypothesis that
      epithelial cells can be a major source of IL-6 when stimulated by bacteria and
      that the adhesive properties of the bacteria can influence this response.

PMID- 1347761
TI  - Use of restriction endonuclease analysis and ribotyping to study epidemiology of
      Pasteurella multocida in closed swine herds.
AB  - One hundred and sixty-four clinical isolates of Pasteurella multocida recovered
      from two swine herds in Minnesota were characterized by restriction endonuclease
      analysis (REA) and rRNA gene restriction fragment length patterns. Bacterial DNA
      was digested with HpaII and electrophoresed in 0.55% agarose. Restriction
      fragments were transferred by Southern blot to nylon membranes and then
      hybridized with digoxigenin-dUTP-labeled Escherichia coli rRNA. Four different
      REA patterns were observed among the 156 serotype A strains isolated from herds A
      and B. The two most common REA types (1 and 2) represented 92% of the strains
      analyzed, while REA types 3 and 4 were observed only in lung samples and
      accounted for 8% of the isolates. Two different ribotypes were observed for these
      serotype A isolates. Ribotype I consisted of the most common types, 1 and 2,
      found by DNA fingerprinting. Ribotype II included REA types 3 and 4. Results from
      both herds suggest that in closed swine populations, a single strain of P.
      multocida predominates and causes disease. It is concluded that these genomic
      fingerprinting techniques were highly discriminatory and that capsular serotyping
      in combination with REA or ribotyping is an appropriate technique for
      epidemiological studies of P. multocida of swine origin.

PMID- 1347760
TI  - Protection of squirrel monkeys against virulent Plasmodium falciparum infections
      by use of attenuated parasites.
AB  - We previously showed that the Uganda Palo Alto line of Plasmodium falciparum
      propagated in Saimiri monkeys and the line maintained in culture in human
      erythrocytes for many years in our laboratory are genetically unrelated (T.
      Fandeur, S. Bonnefoy, and O. Mercereau-Puijalon, Mol. Biochem. Parasitol. 47:167,
      1991). When injected into a splenectomized Saimiri monkey, the in vitro-derived
      Palo Alto population procured a long-lasting, low-grade parasitemia that was
      spontaneously resolved by the animal. This line was propagated by serial blood
      transfers in two other monkeys without enhancement of the virulence of the
      parasites. The genetic characteristics of parasite samples corresponding to the
      different passages of the line in monkeys were stable for the several markers
      examined (pPF11.1, MSA1, and MSA2), although microheterogeneity was detected in
      telomeric and subtelomeric regions of chromosomes. Interestingly, in vitro
      derived Palo Alto parasites induced a strong, potent immunity that enabled the
      monkeys to completely block subsequent challenge with two different heterologous
      lethal P. falciparum lines. These attenuated parasites are thus genetically
      stable in monkeys and represent an attractive model for assessing the feasibility
      of a live attenuated malaria vaccine.

PMID- 1347763
TI  - Xamoterol in severe congestive heart failure: long-term oral treatment, a double
      blind randomised study.
AB  - Twelve patients in severe congestive heart failure were given placebo, 100 mg
      xamoterol (Corwin) twice daily and 200 mg xamoterol twice daily, respectively, in
      3 two-week periods in a double-blind randomised study. At the end of each
      treatment period the patients were evaluated. No differences were found between
      placebo and xamoterol in the following parameters: New York Heart Association
      function group index, heart volume, body weight, exercise duration on bicycle and
      treadmill, heart rate and systolic and diastolic blood pressure at rest. However,
      during exercise we found significantly lower heart rate and rate-pressure product
      during xamoterol treatment. This reduction is probably indicating occupation of
      beta-adrenoreceptors with concomitant reduced oxygen consumption during exercise.

PMID- 1347764
TI  - [Neuron-specific enolase (NSE)--a suitable tumor marker in malignant melanoma?].
AB  - The neuron-specific enolase (NSE) level is elevated in neurons and in numerous
      cells of the APUD system; melanocytes are also considered to belong to this
      system. In order to test the relevance of NSE as a tumour marker for malignant
      melanoma, its concentration in serum was radioimmunologically determined in 89
      patients with melanomas: 24 in stage I (primary tumours), 44 in stage II
      (regional metastases), and 21 in stage III (distant metastases). The average (+/-
      coefficient of variation) concentrations recorded were 7.4 micrograms/l (+/- 46%)
      in patients in stage I, 5.8 micrograms/l (+/- 32%) in those in stage II, and 11.0
      micrograms/l (+/- 72%) in those in stage III. A threshold value of 11.5
      micrograms/l was exceeded in 9 cases, including 8 patients in stage III. Since
      definitely increased values arose almost exclusively in distant metastases,
      determination of NSE levels in serum is hardly a suitable tool for early
      detection of latent metastases.

PMID- 1347762
TI  - Synthetic peptides analogous to the fimbrillin sequence inhibit adherence of
      Porphyromonas gingivalis.
AB  - Fimbriae are important in the adherence of many bacterial species to the surfaces
      they eventually colonize. Porphyromonas (Bacteroides) gingivalis fimbriae appear
      to mediate adherence to oral epithelial cells and the pellicle-coated tooth
      surface. The role and contribution of fimbriae in the binding of P. gingivalis to
      hydroxyapatite (HAP) coated with saliva as a model for the pellicle-coated tooth
      surface were investigated. 3H-labeled P. gingivalis or the radioiodinated
      purified fimbriae were incubated with 2 mg of HAP beads coated with whole human
      saliva (sHAP) and layered on 100% Percoll to separate unbound from sHAP-bound
      components. The radioactivity of the washed beads was a measure of the bound
      components. The binding of P. gingivalis 2561 (381) cells and that of purified
      fimbriae were concentration dependent and saturable at approximately 10(8) cells
      and 40 micrograms of fimbriae added, respectively. The addition of fimbriae
      inhibited binding of P. gingivalis to sHAP beads by 65%, while the 75-kDa
      protein, which is another major surface component of P. gingivalis 2561, did not
      show significant inhibition, suggesting that the fimbriae are important in
      adherence. Encapsulated and sparsely fimbriated P. gingivalis W50 did not bind to
      sHAP beads. On the basis of the predicted sequence of the fimbrillin, a
      structural subunit of fimbriae, a series of peptides were synthesized and used to
      localize the active fimbrillin domains involved in P. gingivalis adherence to
      sHAP beads. Peptides from the carboxyl-terminal one-third of the fimbrillin
      strongly inhibited P. gingivalis binding to sHAP beads. Active residues within
      the sequence of inhibitory peptide 226-245 (peptide containing residues 226 to
      245) and peptide 293-306 were identified by using smaller fragments prepared
      either by trypsin cleavage of the peptide 226-245 or by synthesis of smaller
      segments of peptide 293-306. Hemagglutinin activity, lectinlike binding, and
      ionic interaction did not seem to be involved in this binding since lysine,
      arginine, carbohydrates, and calcium ions failed to affect the binding of P.
      gingivalis. The observation that poly-L-lysine, bovine serum albumin, and
      defatted bovine serum albumin, even at high concentrations, only partially
      blocked the binding of P. gingivalis indicates that hydrophobic interactions are
      not the major forces involved in P. gingivalis binding to sHAP beads. Protease
      inhibitors such as EDTA, leupeptin, pepstatin, 1,10-phenanthroline, and
      phenylmethylsulfonyl fluoride did not interfere with the binding of P.
      gingivalis. However, the binding of P. gingivalis to trypsin- or chymotrypsin
      pretreated sHAP beads was reduced.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1347765
TI  - An investigation of Japanese subjects maps susceptibility to type 1 (insulin
      dependent) diabetes mellitus close to the DQA1 gene.
AB  - Insulin-dependent diabetic and control subjects of Japanese origin were HLA-DRB1,
      -DQB1, and -DQA1 typed using restriction fragment length polymorphism analysis
      and sequence-specific oligonucleotide gene probing. The DQA1 allele DQA1*0301 was
      positively associated with the disease [48/52 (92%) diabetic patients versus
      44/64 (69%) control subjects, Pc less than 0.03, RR = 4.97]. Alleles of the DRB1
      and DQB1 genes showed no significant association with the disease. The frequency
      of DQB1 genotypes encoding the amino acid aspartic acid at position 57 of the DQ
      beta chain did not differ significantly between subjects with insulin-dependent
      diabetes mellitus (IDDM) and controls. These findings suggest that a
      susceptibility allele for IDDM in the Japanese is more closely associated with
      the DQA1 gene than the DQB1 gene.

PMID- 1347766
TI  - Polymorphism of the human CD46 gene in normal individuals and in recurrent
      spontaneous abortion.

PMID- 1347767
TI  - A review of ectoparasites and their effect on cattle production.
AB  - Losses in livestock production due to ectoparasite infestations exceed $2.26
      billion annually. Over 50 species of ectoparasites infest cattle throughout the
      United States. The horn fly, Haematobia irritans (L.), is the most important and
      widespread of the five to six major pest species of pastured cattle in the
      southern region. Results from the examination of production traits from cattle
      under ectoparasite burdens have been variable, ranging from no effect to
      significant reductions in weight gains. Because of this inconsistency, specific
      physiological and nutritional responses in cattle infested or not infested with
      horn flies have been examined. Data have shown significant differences in
      nitrogen retention, blood cortisol concentrations, vital signs, water
      consumption, and urine production. Implications are that total energy balance is
      altered when an animal is exposed to ectoparasite infestations, thereby resulting
      in decreased productivity.

PMID- 1347768
TI  - Sequence of the GLN1 gene of Saccharomyces cerevisiae: role of the upstream
      region in regulation of glutamine synthetase expression.
AB  - The GLN1 gene, encoding glutamine synthetase in Saccharomyces cerevisiae, was
      sequenced, and its encoded polypeptide was shown to have significant homology to
      other eukaryotic glutamine synthetases. S1 analysis has defined the
      transcriptional start site of the gene. Upstream analysis of the gene using lacZ
      fusions has verified transcriptional control of the gene and has identified a
      nitrogen upstream activation sequence which is required for the increased
      transcription of GLN1 seen when glutamine is replaced by glutamate as the
      nitrogen source. cis-acting sites required for the increased transcription in
      response to purine starvation also have been localized.

PMID- 1347770
TI  - Recent developments in the acute somatic treatment of major depression.
AB  - The subtypes of major depression are reviewed, and a decision tree for the acute
      somatic treatment of major depression, including delusional and nondelusional
      depression, is presented. Considerations in clinicians' decisions about
      initiation and selection of acute somatic treatment for patients with major
      depression are then discussed. Current somatic therapies for nondelusional
      depression are described, with emphasis on the mechanisms of action of the drugs
      employed, the relationship between mechanism of action and side effect profile,
      and the selection of a drug on the basis of its side effect profile. The three
      current strategies for the treatment of delusional depression--electroconvulsive
      therapy, the combination of an antidepressant and an antipsychotic agent, and
      amoxapine alone--are then reviewed.

PMID- 1347769
TI  - Structures of chaperonins from an intracellular symbiont and their functional
      expression in Escherichia coli groE mutants.
AB  - An intracellular symbiont harbored by the aphid bacteriocyte, a specialized fat
      body cell, synthesizes in vivo substantially only one protein, symbionin, which
      is a member of the chaperonin-60 family of molecular chaperones. Nucleotide
      sequence determination of the symbionin region of the endosymbiont genome
      revealed that it contains the two-cistron operon sym. Just like the Escherichia
      coli groE operon, the sym operon was dually led by a heat shock and an ordinary
      promoter sequence. According to the nucleotide sequence, symbionin was 85.5%
      identical to GroEL of E. coli at the amino acid sequence level. SymS, another
      protein encoded in the sym operon, which is a member of chaperonin-10, was 79.6%
      identical to GroES. Complementation experiments with E. coli groE mutants showed
      that the chaperonin-10 and chaperonin-60 genes from the endosymbiont are
      expressed in E. coli and that they can function as molecular chaperones together
      with endogenous GroEL and GroES, respectively.

PMID- 1347771
TI  - High-performance liquid chromatographic determination of floctafenine and its
      major metabolite, floctafenic acid in plasma.
AB  - A simple, rapid and selective high-performance liquid chromatographic method for
      the determination of floctafenine and its major metabolite, floctafenic acid, in
      plasma is reported. Plasma samples were purified using the mobile phase as a
      protein precipitant. The supernatant containing parent compounds and diazepam
      (internal standard) were eluted from a 5 micron C 18 reversed-phase column at
      ambient temperature. The mobile phase consisted of 0.05 M sodium
      acetate:acetonitrile: methanol (200:100:100 v/v/v) adjusted to pH 5 and pumped
      isocratically at a flow rate of 1.5 ml/min. The effluent was monitored at 350 nm.
      Quantification was achieved by the measurement of the peak-height ratio of each
      drug to the internal standard. The mean percentage recoveries from plasma samples
      spiked with floctafenine and floctafenic acid ranged from 88.13 to 101.93%.
      Detection limits were 100 ng/ml for floctafenine and 50 ng/ml for floctafenic
      acid. The coefficients of variation (RSD, %) for within-day and day-to-day
      analysis were less than 8%.

PMID- 1347773
TI  - The immunohistochemical expressions of epidermal growth factors, epidermal growth
      factor receptors and c-erbB-2 oncoprotein in human pancreatic cancer.
AB  - The expressions of epidermal growth factors (EGF), epidermal growth factor
      receptors (EGFR), and the c-erbB-2 oncoprotein were immunohistochemically
      examined in 25 cases of human pancreatic carcinoma and epineoplastic pancreatitis
      and in 10 non-cancerous/non-inflammatory pancreatic tissues. The positive rates
      of EGF, EGFR, and the c-erbB-2 oncoprotein in cancer tissues were 72%, 36%, and
      28%, respectively. EGF was stained mainly in the cytoplasm and partly on the
      surfaces of the cancer cells. EGFR and the c-erbB-2 oncoprotein were stained
      mainly on the surfaces of the cancer cells and partly in the cytoplasm. The
      expressions of these 3 products correlated significantly with tumor invasion into
      the anterior and posterior areas surrounding the pancreas. In the EGF, EGFR, and
      c-erbB-2 positive cancer tissues, some stromal cells, that is fibroblasts and
      endothelial cells, were also positive. In the adjacent pancreatic tissues with
      inflammation, these products were noted in some ductal cells, acinar cells,
      fibroblasts and endothelial cells. No distinct staining was detected in non
      cancerous/non-inflammatory tissues. The survival period for patients who tested
      positive for these three proteins was statistically shorter than for those who
      tested negative. These results suggest that the coexpression of EGF and EGFR and
      the expression of the c-erbB-2 oncoprotein are related to the existence of the
      invasion of human pancreatic cancer. Furthermore, an immunohistochemical
      examination of these three products is useful in forming a prognosis for
      pancreatic cancer patients.

PMID- 1347772
TI  - Complete deletion of the androgen receptor gene: definition of the null phenotype
      of the androgen insensitivity syndrome and determination of carrier status.
AB  - The molecular basis of androgen insensitivity was investigated in a family with
      the complete form of the syndrome. Polymerase chain reaction amplification and
      Southern blot analysis of genomic DNA revealed a deletion of the entire androgen
      receptor (AR) gene in affected individuals. The carrier status of female members
      of this family was examined using a HindIII restriction fragment length
      polymorphism associated with the AR gene. Obligate carriers were hemizygous for
      one of the two alleles at this locus, while heterozygosity for the polymorphic
      alleles, implying the presence of two copies of the AR gene, indicated noncarrier
      status. This conclusion was supported by gene dosage studies using comparative
      densitometric analysis of Southern blots hybridized simultaneously with an AR
      cDNA probe and a control cDNA probe from an unrelated gene. Finally, the pattern
      of inheritance of another X-linked DNA polymorphism allowed us to conclude that
      the original mutation had occurred in the germ line of the maternal great
      grandfather of the index patient. Although rare, complete deletion of the AR gene
      is of particular importance in terms of correlation between molecular defect and
      phenotype, as it represents the quintessential form of complete androgen
      insensitivity, the null phenotype.

PMID- 1347774
TI  - Modulation of adhesion of lymphocytes to murine brain endothelial cells in vitro:
      relation to class II major histocompatibility complex expression.
AB  - Adhesion of lymphocytes to mouse brain endothelial cells was studied after
      treatment of the endothelium with 1000 U/ml gamma interferon (IFN-gamma) for 1 h
      to 2 days. Adhesion was not significantly different from controls after 1 h but
      at 4 h and thereafter, adhesion increased in a time-related manner. IFN-gamma
      also increased the expression of class II major histocompatibility complex (MHC)
      and murine intercellular adhesion molecule-1 (ICAM-1) molecules on the
      endothelial cells. The level of expression of class II MHC molecules was related
      to the length of exposure to IFN-gamma. MAb blocking studies suggested that class
      II molecules were responsible for the IFN-gamma-induced increase in lymphocyte
      endothelial cell adhesion. Transfection of a murine lung endothelial cell line
      with cDNA for the class II MHC molecule also produced a significant increase in
      lymphocyte-endothelial cell adhesion, suggesting that the class II MHC molecule
      may have a role in adhesion which is distinct from antigen presentation.

PMID- 1347775
TI  - Identification of DNA-replicating lymphocyte subsets using a new method to label
      the bromo-deoxyuridine incorporated into the DNA.
AB  - A flow cytometric procedure measuring the 5-bromo-2-deoxyuridine incorporated
      into the DNA of cells in S phase was modified to make it compatible with the
      immunofluorescence labelling of cell surface antigens. The modifications were
      introduced at the stages of cell fixation and DNA denaturation. Ethanol was
      replaced by Tween 20-containing paraformaldehyde and hydrochloric acid was used
      for the denaturation of DNA by bovine pancreatic DNase-I. These two modifications
      permitted the preservation of immunofluorescence properties and the use of
      fluorochromes of the phycobiliprotein family such as phycoerythrin and
      allophycocyanin. This new procedure is suitable for evaluating leucocyte subsets
      proliferating in vitro following stimulation. As an illustration the
      immunosuppressive effect of cyclosporin A on PHA stimulated T4-lymphocytes was
      evaluated.

PMID- 1347776
TI  - [XXVI Proceedings of Angiology of the French Language. Paris, 18-20 March 1992.
      Abstracts].

PMID- 1347777
TI  - Perfusion of immobilized isolated nerve terminals as a model for the regulation
      of transmitter release: release of different, endogenous transmitters, repeated
      stimulation, and high time resolution.
AB  - To study the release of neurotransmitters, i.e., the recruitment of transmitters
      for release and the regulation of the release process, isolated nerve terminals
      (synaptosomes) of the rat forebrain were immobilized in Sephadex gel inside a
      perfusion chamber. In this way, the following were achieved: (a) A very limited
      pressure stress was exerted on the synaptosomes, so that these remained viable
      for long periods (greater than 30 min) inside the chamber and did not elute from
      the chamber, which allowed long-term experiments with repeated stimulations; (b)
      estimation of the release of various endogenous transmitters, both in a Ca(2+)
      dependent (exocytotic) and Ca(2+)-independent manner; (c) a step-like stimulation
      with depolarizing agents (rise time, 3-4 s) and a high time resolution (600-ms
      sampling); and (d) negligible reuptake of transmitter into the terminals or
      extracellular breakdown. It is concluded that this perfusion setup helps to
      provide new insights in the presynaptic stimulus-secretion coupling, co
      transmission, and the exo-endocytosis cycle.

PMID- 1347778
TI  - Effect of histamine H2 receptor antagonists on the secretion of cerebrospinal
      fluid in the cat.
AB  - Following a recent report that epithelial cells of the choroid plexus possess
      histamine H2 receptors, the effect of cimetidine and ranitidine, histamine H2
      receptor antagonists, on the secretion and electrolyte content of CSF was
      examined. Fifty cats were divided into one control (n = 6) and six experimental
      groups. CSF was collected by puncture of the cisterna magna following
      pentobarbital anesthesia, and its volume, concentrations of Na+, K+, Cl-, and pH
      were determined. Cimetidine or ranitidine (50, 20, or 10 mg/kg) was injected
      intravenously 2 h after the start of the test, and their concentrations were
      measured in hourly blood samples and in 30-min aliquots of CSF in the 50 mg/kg
      experimental groups. Whereas the secretion of CSF did not change over 6 h in the
      control group, it decreased significantly by 30-60 min after injection of
      cimetidine or ranitidine and remained low for the following 6 1/2 h in all
      experimental groups except the 10-mg ranitidine group. Peak cimetidine and
      ranitidine concentrations in CSF in the 50-mg experimental groups were noted 60
      and 90 min, respectively, after intravenous injection. CSF electrolyte
      concentrations and pH did not change during the test in any group. We conclude
      that intravenous cimetidine or ranitidine can significantly reduce CSF secretion
      in the cat, possibly by competitive inhibition of the histamine effect on H2
      receptors located on the choroid plexus epithelial cell, or by a direct effect on
      the capillaries of the choroid plexus.

PMID- 1347779
TI  - D1 dopamine receptor activation of multiple transcription factor genes in rat
      striatum.
AB  - Recent studies have shown that dopamine receptor agonists induce expression of
      Fos-like immunoreactivity in rat striatal neurons. The protooncogene c-fos
      belongs to a family of immediate early genes that are rapidly induced in
      fibroblasts by growth factors. In light of previous findings that several
      immediate early gene mRNAs that encode proven or putative transcription factors
      are differentially regulated by neuronal stimulation in vivo, we have examined
      the effect of dopaminergic agents on mRNA levels of several such genes using in
      situ hybridization and northern blot analysis. d-Amphetamine (2.5-10 mg/kg i.p.)
      causes a rapid but transient dose-dependent increase in zif268 and jun-B mRNA
      levels in striatum that was abolished by striatal 6-hydroxydopamine lesions or by
      pretreatment with the specific D1 receptor antagonist SCH-23390 but not by
      specific D2 receptor antagonists. Apomorphine, a dopamine agonist that acts at
      both D1 and D2 receptors, and SKF-38393, a specific D1 receptor agonist, produce
      similar mRNA changes in rats pretreated with either 6-hydroxydopamine or
      reserpine, whereas LY-171,555, a specific D2 receptor agonist, has no effect.
      Direct dopamine agonist effects on these immediate early gene mRNA levels are
      also blocked by D1 but not by D2 antagonists. We observed similar, although less
      robust, changes in c-fos and fos-B mRNA levels. These results demonstrate that
      striatal D1 dopamine receptors are coupled to activation of multiple
      transcription factor genes, including zif268 and jun-B as well as members of the
      fos family.

PMID- 1347780
TI  - Clonidine inhibition of norepinephrine release from normal and morphine-tolerant
      guinea pig cortical slices.
AB  - Endogenous norepinephrine (NE) release in cerebral cortex slices taken from
      normal and morphine-tolerant guinea pigs was measured by HPLC. In normal slices,
      a linear relationship was found between electrically evoked NE release and the
      log of the frequency of stimulation in the range of 1-20 Hz. The efficiency of
      the alpha 2-mediated autofeedback was tested by adding the alpha 2-agonist
      clonidine and the alpha 2 agonist idazoxan. NE release was dose-dependently
      reduced by clonidine (1 nmol/L-1 mumol/L) and increased by idazoxan (10-100
      nmol/L). The inhibition by clonidine was significantly greater at 1 Hz than at 3
      Hz, whereas the absolute increase in NE release induced by idazoxan was greater
      at 3 Hz than at 1 Hz. Morphine at 1 mumol/L (a concentration per se ineffective)
      shifted to the left the clonidine concentrations able to inhibit NE release at 3
      and 1 Hz (1-10 nmol/L), but at both frequencies, the opiate reduced the maximal
      inhibition induced by clonidine at 1 mumol/L. In slices taken from morphine
      tolerant guinea pigs (in the presence of morphine at 1 mumol/L), clonidine (1
      nmol/L-1 mumol/L) was ineffective at the stimulation rate of 3 Hz, but it was
      more active than in normal slices at 1 Hz. Such a response pattern suggests a
      reduced availability of alpha 2 receptors and an increase in their sensitivity to
      clonidine. However, chronic morphine treatment did not influence the
      physiological autoinhibition because the increase in NE release elicited by
      idazoxan (10-100 nmol/L) at 1 and 3 Hz was the same in normal and in "morphine
      tolerant" slices.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347781
TI  - Putative neurotoxicity of SKF 38393 and other D1 dopaminergic drugs investigated
      in rat striatum.
AB  - The recently alleged neurotoxicity of the D1 receptor agonist, SKF 38393, was
      investigated in rat striatum by measuring the enzymes acetylcholinesterase (AChE)
      and glutamate decarboxylase (GAD). First, unilateral intrastriatal microinjection
      of the excitotoxin kainic acid (2 micrograms in 1 microliter) was shown to evoke
      vigorous contraversive circling, followed 1 or 2 weeks later by profound
      decreases in striatal AChE (24 and 54%), GAD (51 and 75%), and protein (36 and
      47%), as well as loss of GAD (45% at 2 weeks) in the ipsilateral substantia
      nigra. Similar striatal treatments with SKF 38393 (30 micrograms in 0.5-1
      microliter), the related benzazepines SKF 82526 (D1 agonist, 30 micrograms in 1
      microliter) and SCH 23390 (D1 antagonist, 5 micrograms in 1 microliter), or the
      phenanthridine D1 agonist CY 208-243 (5 micrograms in 1 microliter) failed to
      affect the rats' behaviour or their striatal levels of AChE, GAD, and protein.
      Intrastriatal SKF 38393 (30 micrograms in 0.5 microliter) also had no influence
      on these enzymes in the substantia nigra. It is concluded that none of the D1
      dopaminergic compounds examined here was neurotoxic toward the many different
      cell groups that contain AChE and/or GAD in the striatum.

PMID- 1347782
TI  - The unc-18 gene encodes a novel protein affecting the kinetics of acetylcholine
      metabolism in the nematode Caenorhabditis elegans.
AB  - Genes affecting acetylcholine (ACh) levels without influencing choline
      acetyltransferase activity have been identified in Caenorhabditis elegans. We
      have examined one such gene, unc-18. We isolated a transposon-insertion allele
      for unc-18 and used it to clone a genomic region containing the unc-18 locus. The
      unc-18 location within this region was determined by rescuing the unc-18 mutant
      phenotype in a germ-line transformation experiment and identifying transcripts
      affected by four independent unc-18 mutations. A single-sized poly(A)+ RNA was
      synthesized from the gene. Expression of the transcript appears to be stage
      specific: The transcript is found in abundance at the early larval stage but in
      decreased amounts at the fourth larval and the adult stages. These results show
      that the unc-18 gene plays a role in development as well as in the kinetics of
      ACh metabolism.

PMID- 1347783
TI  - Regulation of tyrosine hydroxylase gene expression in the rat carotid body by
      hypoxia.
AB  - The activity (Vmax) of tyrosine hydroxylase (TH; EC 1.14.16.2), the rate limiting
      enzyme in the synthesis of catecholamines, is increased in carotid body, superior
      cervical ganglion, and the adrenal medulla during hypoxia (i.e., reduced PaO2).
      The present study was undertaken to determine if the increase in TH activity in
      these tissues during hypoxia is regulated at the level of TH mRNA. Adult rats
      were exposed to hypoxia (10% O2) or room air for periods lasting from 1 to 48 h.
      The carotid bodies, superior cervical ganglia, and adrenals were removed and
      processed for in situ hybridization using 35S-labeled oligonucleotide probes. The
      concentration of TH mRNA was increased by hypoxia at all time points in carotid
      body type I cells, but not in cells of either superior cervical ganglion or
      adrenal medulla. The increase in TH mRNA in carotid body during hypoxia did not
      require innervation of the carotid body or intact adrenal glands. In addition,
      hypercapnia, another physiological stimulus of carotid body activity, failed to
      induce an increase in TH mRNA in type I cells. Our findings suggest that hypoxia
      stimulates TH gene expression in the carotid body by a mechanism that is
      intrinsic to type I cells.

PMID- 1347784
TI  - Regional distribution of alpha 2A- and alpha 2B-adrenoceptor subtypes in
      postmortem human brain.
AB  - The newly available and highly selective radiolabeled antagonist [3H]RX 821002
      was used to examine the distribution of alpha 2 adrenoceptors in human brain.
      High densities of alpha 2 adrenoceptors were found in the hippocampus, frontal
      cortex, thalamus, amygdala, pons, and medulla oblongata. Intermediate densities
      were observed in the striatum (nucleus accumbens, nucleus caudatus, and putamen),
      globus pallidus, and substantia nigra. The KD values for [3H]RX 821002 were
      similar in all regions (ranging from 2.8 to 7.5 nM). On the basis of their
      different affinities for prazosin and oxymetazoline, the alpha 2 adrenoceptors
      have been divided into alpha 2A and alpha 2B subtypes. To examine the alpha
      2A/alpha 2B-adrenoceptor ratio in the different brain regions, we performed
      oxymetazoline and prazosin/[3H]RX 821002 competition binding experiments. In
      frontal cortex membranes, the competition curves with prazosin were steep,
      indicating a single class of binding sites, whereas the competition curves with
      oxymetazoline were shallow and fitted by computer best to a two-site model.
      However, in the presence of GTP, the high-affinity sites for oxymetazoline were
      partially converted into low-affinity sites, indicating that this agonist
      interacts with high- and low-affinity states of the alpha 2 adrenoceptors. This
      implies that oxymetazoline is not very suitable for discriminating the alpha 2A-
      and alpha 2B-receptor subtypes in radioligand binding studies. Therefore,
      prazosin/[3H]RX 821002 competition binding experiments were used to investigate
      the distribution of the alpha 2-adrenoceptor subtypes in human brain. The alpha
      2A-receptor subtype was detected in all brain regions examined. In contrast,
      alpha 2B receptors were only observed in striatum and globus pallidus.

PMID- 1347785
TI  - Seizures during detoxification.

PMID- 1347786
TI  - Choosing between apples and apples: physicians' choices of prescription drugs
      that have similar side effects and efficacies.
AB  - OBJECTIVE: To examine physician choices of commonly used medications having
      similar side effects and efficacies, and to evaluate factors that may affect
      these choices. DESIGN/SETTING: Cross-sectional survey conducted in winter 1989
      1990. PARTICIPANTS: 263 physicians at a university teaching hospital (response
      rate = 71%). MEASUREMENTS AND MAIN RESULTS: Physicians rated patient compliance,
      cost to patient, and patient preference as the three most influential factors in
      their selection of a particular agent from a class of similar drugs. Housestaff
      were less likely than faculty to consider cost to patient as a "very important"
      factor (33% vs. 60%; p less than 0.05), and only 11% of all physicians felt that
      cost to third-party payer was very important. Physicians reported that their
      choices of particular nonsteroidal anti-inflammatory drugs (NSAIDs), histamine-2
      (H2) blockers, and inhaled beta-agonists were mainly determined by which drugs
      enhanced compliance or were used by others (the "traditional choice"); cost to
      patient was a less important influence in these instances. All physician
      subgroups were inaccurate in predicting the approximate prices of their first-
      and second-choice agents. For example, only 28% of those selecting naproxen as
      their preferred NSAID were within $10 of the range of the prices of a one-month
      supply, and 14% were within $10 for cimetidine. CONCLUSION: Although this group
      of physicians reported considering drug costs to be important when choosing
      between similar drugs, they acknowledged that cost was relatively unimportant in
      several specific instances studied and their knowledge of the absolute and
      relative prices of drugs they commonly prescribed was deficient.

PMID- 1347787
TI  - Comparison by race of total serum IgG, IgA, and IgM with CD4+ T-cell counts in
      North American persons infected with the human immunodeficiency virus type 1.
AB  - European patients with human immunodeficiency virus type 1 (HIV-1) infection have
      been reported to have lower titers of anti-p24 antibody than Central African HIV
      seropositive patients. Recently, black HIV positive patients in the United States
      were reported to be more likely to have detectable anti-p24 antibodies, less p24
      antigenemia, and higher combined serum immunoglobulins than white HIV positive
      patients. We measured individual total serum immunoglobulins in 853 HIV positive
      patients (94% male; 58% white and 42% black) on their initial medical evaluation
      and compared them with CD4+ T-cell counts. Blacks had notably higher IgG levels
      (p = 0.001) across the entire spectrum of CD4+ T-cell counts. Serum IgM levels
      were slightly higher in blacks. IgA levels were not significantly different
      between the races, although the trend (p = 0.006) was toward higher levels in
      whites. We also measured these three serum immunoglobulins in 60 HIV
      seronegative, healthy blood donors (30 black and 30 white). In this control
      group, blacks had statistically higher IgG and IgA levels than whites. A review
      of the literature prior to the HIV/acquired immune deficiency syndrome epidemic
      also supports the view that racial differences in IgG levels are not specific for
      HIV infection. We speculate that racial differences in humoral immunity,
      independent of geography or strain of HIV, may account for differences in anti
      HIV antibody levels and HIV antigenemia.

PMID- 1347788
TI  - DNA polymorphisms of the human CD46 gene in fetal and adult tissues.
AB  - DNA polymorphisms of the CD46 gene were investigated using a full length cDNA
      probe and five different restriction enzymes in genomic DNA samples from human
      fetal tissues and adult peripheral blood leukocytes. A HindIII polymorphism was
      observed and was classed as Types I, II and III at a ratio of approximately
      3.5:2:1, depending on the presence or absence of two polymorphic fragments of 4.5
      and 2.0 kb. No variation of polymorphic distribution was evident between the
      fetal and adult samples. Whether variation in CD46 expression between maternal
      and fetal tissue is relevant to fetal viability in pregnancy remains to be
      established.

PMID- 1347789
TI  - Another death from Ecstacy.

PMID- 1347790
TI  - Small atrial natriuretic peptide analogues: design, synthesis, and structural
      requirements for guanylate cyclase activation.
AB  - Structure/activity studies on atrial natriuretic peptide ANP (1-28) have
      highlighted three portions of the native molecule as necessary for its biological
      responses. We have linked these three regions and excised the remaining segments
      to produce a family of small analogues (less than half the size of the parent)
      which demonstrate the full range of ANP's actions. Importantly, these compounds
      act at both major types of ANP receptor. Two critical modifications lead to more
      potent analogues; both involve expanding the cyclic portion of the molecule.
      Further optimization of one of these modified structures leads to A68828, a full
      ANP agonist which shows promise as a preventative agent against acute renal
      failure.

PMID- 1347791
TI  - Analgesic dipeptide derivatives. 7. 3,7-Diamino-2-hydroxyheptanoic acid (DAHHA)
      containing dipeptide analogues of the analgesic compound H-Lys-Trp(Nps)-OMe.
AB  - A series of diastereomeric dipeptides, analogues of the analgesic compound H-Lys
      Trp(Nps)-OMe (2), containing 3,7-diamino-2-hydroxyheptanoic acid (DAHHA) and 2
      [(o-nitrophenyl)sulfenyl]tryptophan [Trp(Nps)] has been synthesized. These
      compounds were tested as enkephalin-degrading aminopeptidases (APs), AP-M and AP
      B inhibitors, and analgesics. The inhibitory potencies and the antinociceptive
      effects depended on the stereochemistry of the compounds. (2S,3R)-DAHHA-L
      Trp(Nps)-OMe (26d) was a highly potent and selective enkephalin-degrading APs
      inhibitor, with an IC50 value in the 10(-8) M range. Although this derivative was
      about 10(3)-fold more potent than 2 against these enzymes, their antinociceptive
      effects were completely similar. These results indicate that the inhibitory
      capacity of this series of Trp(Nps)-containing dipeptides against enkephalin
      degrading enzymes is not an important factor for their antinociceptive effects.

PMID- 1347792
TI  - Use of contour-clamped homogeneous electric field (CHEF) electrophoresis to type
      methicillin-resistant Staphylococcus aureus.
AB  - Strains of methicillin-resistant Staphylococcus aureus (MRSA) from Australia and
      the UK were compared by digesting their chromosomal DNA with the low-frequency
      cutting restriction enzyme SmaI and separating the restriction fragment length
      polymorphisms (RFLPs) by contour-clamped homogeneous electric field (CHEF)
      electrophoresis. The numbers of restriction fragments produced were in the range
      14-17 and the sizes of the bands were 7-700 kb. Generally, the results confirmed
      previous conclusions based on antimicrobial resistance and plasmid profiles. The
      earlier MRSA isolates were different from more recent isolates, and the epidemic
      MRSA from eastern Australia (EA MRSA) was the same as the epidemic MRSA (EMRSA)
      found in London hospitals. However, contrary to previous results, the EA MRSA did
      not constitute a homogeneous group. The results showed that comparison of RFLPs
      by CHEF electrophoresis is a useful technique for studying the epidemiology of
      MRSA.

PMID- 1347793
TI  - The vaccinia virus K3L gene product potentiates translation by inhibiting double
      stranded-RNA-activated protein kinase and phosphorylation of the alpha subunit of
      eukaryotic initiation factor 2.
AB  - Interferon resistance of vaccinia virus is mediated by specific inhibition of
      phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2
      alpha) by the double-stranded-RNA-activated (DAI) protein kinase. Vaccinia virus
      encodes a homolog of eIF-2 alpha, K3L, the deletion of which renders the virus
      sensitive to interferon treatment. We have studied the mechanism by which this
      protein product elicits interferon resistance in a transient DNA transfection
      system designed to evaluate regulators of eIF-2 alpha phosphorylation. In this
      system, translation of a reporter gene mRNA is inefficient because of eIF-2
      phosphorylation mediated by the DAI protein kinase. Cotransfection of the K3L
      gene enhances translation of the reporter mRNA in this system. The K3L protein
      inhibits eIF-2 alpha phosphorylation and DAI kinase activation, apparently
      without being phosphorylated itself. Inhibition of protein synthesis, elicited by
      expression of a mutant Ser-51----Asp eIF-2 alpha designed to mimic a
      phosphorylated serine, is not relieved by the presence of K3L, suggesting that
      K3L cannot bypass a block imposed by eIF-2 alpha phosphorylation. The results
      suggest that K3L acts as a decoy of eIF-2 alpha to inhibit DAI kinase
      autophosphorylation and activation. Another vaccinia virus gene product, K1L,
      which is required for growth of vaccinia virus on human cells, does not enhance
      translation in this assay.

PMID- 1347794
TI  - Stimulation of lymphokines in Jurkat cells persistently infected with vaccinia
      virus.
AB  - The response of the human CD4+ T-cell line Jurkat to infection with vaccinia
      virus was investigated. Virus titers peaked approximately 3 to 4 days after
      infection, while cell growth paralleled that of uninfected cells, indicating that
      growth rates were not appreciably affected by viral infection. Results from
      plaque assays and fluorescence-activated cell sorter (FACS) analyses of virus
      antigens demonstrated that a persistent infection in which the percentage of
      infected cells and the virus titers fluctuated from passage to passage was
      established. Further characterization of the persistent infection revealed that
      the virus influences cellular functions. Induction of interleukin-2 (IL-2) and IL
      2 receptor alpha (IL-2R alpha) in Jvac cells was shown by enzyme-linked
      immunosorbent assay and FACS analysis, respectively. Hybridization of cellular
      RNA with cloned probes confirmed the increased IL-2 expression and demonstrated
      that Jvac cells also expressed more IL-6 but not gamma interferon (IFN-gamma) or
      IL-1 beta. Dual-antibody staining and FACS analysis for vaccinia virus antigens
      and IL-2R alpha indicated that IL-2R alpha expression was restricted to the
      infected cells. Jvac cells were also resistant to superinfection, an additional
      proof that persistent infection elicited phenotypic changes in the cell
      population.

PMID- 1347795
TI  - Biochemical and physical properties of the prion protein from two strains of the
      transmissible mink encephalopathy agent.
AB  - Transmissible mink encephalopathy (TME) has been transmitted to Syrian golden
      hamsters, and two strains of the causative agent, HYPER (HY) and DROWSY (DY),
      have been identified that have different biological properties. During scrapie, a
      TME-like disease, an endogenous cellular protein, the prion protein (PrPC), is
      modified (to PrPSc) and accumulates in the brain. PrPSc is partially resistant to
      proteases and is claimed to be an essential component of the infectious agent.
      Purification and analysis of PrP from hamsters infected with the HY and DY TME
      agent strains revealed differences in properties of PrPTME sedimentation in N
      lauroylsarcosine, sensitivity to digestion with proteinase K, and migration in
      polyacrylamide gels. PrPC and HY PrPTME can be distinguished on the basis of
      their relative solubilities in detergent and protease sensitivities. PrPTME from
      DY-infected brain tissue shared solubility characteristics of PrP from both
      uninfected and HY-infected tissue. Limited protease digestion of PrPTME revealed
      strain-specific migration patterns upon polyacrylamide gel electrophoresis.
      Prolonged proteinase K treatment or N-linked deglycosylation of PrPTME did not
      eliminate such differences but demonstrated the PrPTME from DY-infected brain was
      more sensitive to protease digestion than HY PrPTME. Antigenic mapping of PrPTME
      with antibodies raised against synthetic peptides revealed strain-specific
      differences in immunoreactivity in a region of the amino-terminal end of PrPTME
      containing amino acid residues 89 to 103. These findings indicate that PrPTME
      from the two agent strains, although originating from the same host, differ in
      composition, conformation, or both. We conclude that PrPTME from the HY and DY
      strains undergo different posttranslational modifications that could explain
      differences in the biochemical properties of PrPTME from the two sources. Whether
      these strain-specific posttranslational events are directly responsible for the
      distinct biological properties of the HY and DY agent strains remains to be
      determined.

PMID- 1347796
TI  - Multiple isolates and characteristics of human T-cell leukemia virus type II.
AB  - Human T-cell leukemia (or lymphotropic) virus type II (HTLV-II) was isolated from
      eight HTLV-seropositive patients, six of whom were also infected with human
      immunodeficiency virus, by cocultivation of peripheral blood mononuclear cells
      (PBMCs) with BJAB, a continuous B-cell line. Restriction endonuclease mapping of
      the proviruses demonstrated consistent differences among isolates, and two
      distinct physical map patterns were observed. The results suggest the existence
      of two closely related molecular subtypes of HTLV-II, which are tentatively
      designated HTLV-IIa and HTLV-IIb. This finding was supported by preliminary
      nucleotide sequence analysis of the env gene region encoding the transmembrane
      glycoprotein gp21, which showed consistent differences between the two proposed
      virus subtypes. Exploitation of differences in restriction endonuclease sites
      allowed polymerase chain reaction amplification to detect and differentiate the
      two subtypes in fresh PBMCs of HTLV-seropositive intravenous drug abusers
      (IVDAs). The results of these studies confirm that HTLV-II infection is the
      prominent HTLV infection in seropositive IVDAs and also show that infection with
      both subtypes occurs. The finding of genetic heterogeneity in the HTLV-II group
      of viruses may have important implications for studies on its role in human
      disease and will be useful in characterizing the viruses present in newly
      discovered endemic foci in New World indigenous populations.

PMID- 1347798
TI  - Differential effects of LHRH and somatostatin analogs on human breast cancer.
AB  - We have been interested in the possible direct effects of luteinizing hormone
      releasing hormone (LHRH) and somatostatin (SS) analogs on the growth of human
      mammary tumor cells. Four recently synthesized peptide hormones including the
      LHRH agonists D-Trp6-LHRH and zoladex, LHRH antagonists SB30 and SB75, and the
      somatostatin analog RC 160 were analyzed for their effects on DNA synthesis of
      MCF-7 breast cancer cells in culture. At 48 hr, D-Trp6-LHRH and SB30 did not show
      significant effects (dose range, 10(-12)-10(-6) M). However, the combination of
      these two peptides at 10(-10) M produced significant inhibition of 3[H]thymidine
      incorporation (50% control). At 72 hr in the absence of estradiol-stimulated
      growth, D-Trp6-LHRH showed inhibition at 10(-12) and 10(-10) M (P less than 0.005
      and 0.001). At higher concentrations, no significant inhibition was noted. In
      contrast to D-Trp6, SB30 (antagonist) showed no inhibition but significant
      stimulation of DNA synthesis at 10(-6) and 10(-4) M. In the presence of added
      estradiol (10(-9) M), complete reversal of D-Trp6-LHRH analog inhibition is
      noted. In contrast, there is persistent stimulation by SB30 (P less than 0.001).
      At 96 hr, D-Trp6-LHRH continued to show maximal inhibition of 70% in the absence
      of estradiol. SB30 stimulated DNA synthesis 100% at 10(-6) M. At 72 hr, the SS
      analog RC 160 demonstrated significant inhibition (53%) that was similar to D
      Trp6 and SB75 peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347799
TI  - Brucine lethality in mice.

PMID- 1347797
TI  - Influence of carbohydrate moieties on the immunogenicity of human
      immunodeficiency virus type 1 recombinant gp160.
AB  - The role of carbohydrates in the immunogenicity of human immunodeficiency virus
      type 1 (HIV-1) glycoproteins (gp160 and gp120) remains poorly understood. We have
      analyzed the specificity and neutralizing capacity of antibodies raised against
      native gp160 or against gp160 deglycosylated by either endo F-N glycanase,
      neuraminidase, or alpha-mannosidase. Rabbits immunized with these immunogens
      produced antibodies that recognized recombinant gp160 (rgp160) from HIV-1 in a
      radioimmunoassay and in an enzyme-linked immunosorbent assay. Antibodies elicited
      by the different forms of deglycosylated gp160 were analyzed for their reactivity
      against a panel of synthetic peptides. Compared with anti-native gp160 antisera,
      serum reactivity to most peptides remained unchanged, or it could increase
      (peptide P41) or decrease. Only antibodies raised against mannosidase-treated
      gp160 failed to react with a synthetic peptide (peptide P29) within the V3 loop
      of gp120. Rabbits immunized with desialylated rgp160 generated antibodies which
      recognized not only rgp160 from HIV-1 but also rgp140 from HIV-2 at high titers.
      Although all antisera produced against glycosylated or deglycosylated rgp160
      could prevent HIV-1 binding to CD4-positive cells in vitro, only antibodies
      raised against native or desialylated gp160 neutralized HIV-1 infectivity and
      inhibited syncytium formation between HIV-1-infected cells and noninfected CD4
      positive cells, whereas antibodies raised against alpha-mannosidase-treated gp160
      inhibited neither virus replication nor syncytium formation. These findings
      indicate that the carbohydrate moieties of gp160 can modulate the specificity and
      the protective efficiency of the antibody response to the molecule.

PMID- 1347800
TI  - Immunoglobulin prophylaxis against HTLV-I in a rabbit model.
AB  - We have investigated the protective effect of human T-cell leukemia virus I (HTLV
      I) immune globulin (HTLVIG) against HTLV-I in rabbits. HTLVIG containing 77 mg/ml
      of IgG was prepared from pooled plasma from seropositive healthy persons. In the
      first experiment, four groups (A, B, C, and D) of three rabbits were transfused
      with 5 ml blood from an HTLV-I-infected rabbit. Groups A, B, and C were infused
      24 h later with 10, 5, and 2 ml HTLVIG, respectively, while group D was infused
      with 10 ml HTLVIG 48 h later. Seroconversion for HTLV-I occurred in none of group
      A, one of group B, and all of groups C and D after 2-5 weeks. In the second
      experiment, four litters (E, F, G, and H) born to another virus-infected rabbit
      and consisting of 7, 5, 7, and 7 newborns, respectively, were used. Litters E and
      H were allowed to grow normally as controls, while litters F and G were given
      intraperitoneal inoculation of 3 ml/kg of HTLVIG weekly four times until weaning.
      Although three of litters E and H each seroconverted after 5-8 weeks, none of
      litters F, and one of litter G became antibody-positive after 10 weeks. Presence
      or absence of HTLV-I infection in all these animals was confirmed by transfusion
      assay or gene amplification. These results indicate that passive immunization
      protects rabbits against blood- and milk-borne transmission of HTLV-I.

PMID- 1347801
TI  - ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator
      vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases
      of suspected acute myocardial infarction. ISIS-3 (Third International Study of
      Infarct Survival) Collaborative Group.
AB  - 41,299 patients entering 914 hospitals up to 24 h (median 4 h) after the onset of
      suspected acute myocardial infarction were randomised between streptokinase (SK:
      1.5 MU infused over about 1 h), tissue plasminogen activator (tPA, duteplase:
      0.60 MU/kg infused over about 4 h), or anisoylated plasminogen-streptokinase
      activator complex (APSAC), anistreplase: 30 U over about 3 min). All patients
      were to receive aspirin (162 mg/day enteric-coated), with the first tablet chewed
      for rapid and full antiplatelet effect. Half of all patients were randomly
      allocated subcutaneous calcium heparin (12,500 IU starting at 4 h and given twice
      daily for 7 days or until prior discharge) in addition to aspirin, and the other
      half were to receive aspirin alone. ASPIRIN PLUS HEPARIN VERSUS ASPIRIN ALONE-
      The addition of heparin to aspirin was associated with an excess of transfused or
      other major non-cerebral bleeds (1.0% aspirin plus heparin vs 0.8% aspirin alone;
      2p < 0.01) and of definite or probable cerebral haemorrhage (0.56% vs 0.40%; 2p <
      0.05), but with no significnat differences in total stroke (1.28% vs 1.18%).
      Reinfarctions were slightly less common among those allocated aspirin plus
      heparin (3.16% vs 3.47%; 2p = 0.09). There was no signficant difference in the
      pre-specified endpoint of 35-day mortality (2132 [10.3%] aspirin plus heparin vs
      2189 [10.6%] aspirin alone). During the scheduled heparin treatment period there
      were slightly fewer deaths in the aspirin plus heparin group (days 0-7 in
      hospital: 1534 [7.4%] vs 1633 [7.9%]; 2 p = 0.06), with a slight convergence by
      day 35 (598 further deaths [3.1% of survivors] vs 556 [2.9%]). The pattern was
      similar to that observed in the GISSI-2 trial, so that in both trials combined
      there was a significant reduction in mortality during the scheduled treatment
      period (2071 [6.8%] vs 2239 [7.3%]; 2p < 0.01). This indicates avoidance of 5
      deaths (SD 2) per 1000 patients allocated this high-dose subcutaneous heparin
      regimen in addition to aspirin, but some of any early benefit may be lost after
      heparin ceases, with no significant mortality advantage in days 0-35 (both
      trials: 3100 [10.0%] vs 3172 [10.2%]) or during follow-up to 6 months. SK VERSUS
      APSAC--APSAC was associated with significantly more reports of allergy causing
      persistent symptoms and of non-cerebral bleeds, but not of transfused bleeds or
      of reinfarctions. There was a slight excess of strokes with APSAC (1.04% SK vs
      1.26% APSAC; 2p = 0.08), much of it appearing soon after treatment started
      (strokes during days 0-1: 0.50% SK vs 0.73% APSAC; 2p < 0.02) and being
      attributed to cerebral haemorrhage (0.24% SK vs 0.55% APSAC; 2p < 0.0001). No
      significant difference was observed in reinfarction (3.47% SK vs 3.55% APSAC).
      There was no significant mortality difference during days 0-35, either among all
      randomised patients (1455 [10.6%] SK vs 1448 [10.5%] APSAC) or among the pre
      specified subset presenting within 0-6 h of pain onset and with ST elevation on
      the electrocardiogram in whom fibrinolytic treatment may have most to offer (861
      [10.0%] SK vs 855 [9.9%] APSAC). No significant difference in 6-month survival
      was apparent overall or in the subset.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1347802
TI  - Identification by molecular cloning of an autoantigen associated with Addison's
      disease as steroid 17 alpha-hydroxylase.
AB  - Idiopathic Addison's disease is characterised by a progressive failure in the
      synthesis of all classes of steroid hormones and by an immune response against
      the steroid-producing cells of the adrenal cortex; the nature of the adrenal
      autoantigens is not known. We have used molecular cloning and sequencing to
      identify the target antigens. We screened a human fetal adrenal cDNA expression
      library in lambda gt11 vector with serum samples from patients with Addison's
      disease as part of the type 1 polyendocrine autoimmunity syndrome. Samples from 3
      patients, which had precipitating antibodies against two adrenal proteins
      detected by immunodiffusion and against five adrenal proteins of molecular mass
      55, 48, 43, 39, and 19 kDa as judged by immunoblotting, were used to identify 60
      immunoreactive clones. 39 of these were subcloned, inserted into the M13mp10
      vector, and sequenced by the dideoxy method or identified by Southern and dot
      blot hybridisation. All but 1 of the inserts showed more than 98.8% homology with
      the published sequence of steroid 17 alpha-hydroxylase. This protein was
      expressed by insertion of 1 of the clones into the pGEMEX-1 vector. Only serum
      from patients with Addison's disease and type 1 polyendocrine autoimmunity
      syndrome that reacted with the 55 kDa adrenal protein recognised the recombinant
      17 alpha-hydroxylase protein on immunoblotting. Our results show that one of the
      key enzymes in steroid biosynthesis, 17 alpha-hydroxylase, is an autoantigen
      involved in the pathogenesis of adrenocortical failure.

PMID- 1347803
TI  - Recombinant human erythropoietin for autologous blood donation: effects on
      perioperative red-blood-cell and serum erythropoietin production.
AB  - To speed collection of blood for autologous transfusion during elective surgery,
      patients may be given recombinant human erythropoietin (r-HuEPO). In a controlled
      trial, we evaluated the effects of r-HuEPO on perioperative red-blood-cell and
      serum erythropoietin (s-EPO) production in patients donating blood before
      elective orthopaedic surgery. Patients were assigned randomly to receive no r
      HuEPO (12 patients), or 3000 U (4), 6000 U (5), or 9000 U (4) of r-HuEPO
      intravenously twice a week from the time of the first blood donation. All
      patients received iron sulphate. 1200 ml blood was collected from each patient in
      three weekly donations of 400 ml. The 3000, 6000, and 9000 U treatment groups
      produced 284, 350, and 383 ml, respectively, of red cells during donation, and
      the untreated controls produced 211 ml. s-EPO concentrations were within the
      normal range during donation. After surgery, s-EPO concentrations peaked on
      postoperative day 1 in untreated patients and on day 7 in treated patients;
      therefore, r-HuEPO may suppress endogenous erythropoietin secretion. Although
      administration of r-HuEPO increases production of red blood cells, the
      preoperative anaemia induced by repeated phlebotomy without r-HuEPO may
      accelerate the postoperative secretion of endogenous erythropoietin.

PMID- 1347804
TI  - Choriodecidual production of interleukin-8 and mechanism of parturition.
AB  - Both prostaglandins and antiprogestagens can induce labour and ripen the cervix,
      but the mechanisms are unclear. The collagenases that bring about cervical
      ripening are neutrophil derived. We examined the potential of uterine tissues to
      control neutrophil attraction by measuring interleukin-8 production.
      Choriodecidual cells in culture produced substantial amounts of interleukin-8;
      release was inhibited by progesterone and stimulated by the antiprogestagen
      mifepristone. Interleukin-8 production was similar in cells from spontaneously
      delivered placentas and from those obtained at caesarean section. Since
      prostaglandin E and interleukin-8 have synergistic effects, we suggest that
      interleukin-8 activity is the final common step of prostaglandin and
      antiprogestagen action in parturition.

PMID- 1347805
TI  - Induction of thromboses within renal grafts by high-dose prophylactic OKT3.
AB  - Among 93 consecutive kidney-transplant patients who received prophylactic OKT3 10
      mg/day for 2 weeks, 9 had intragraft thromboses within 2 weeks of
      transplantation. The thromboses were in graft artery in 1 patient and veins in 3.
      The other 5 had thromboses in glomerular capillaries and thrombotic
      microangiopathy similar to that of haemolytic-uraemic syndrome. All attempted
      treatments failed, and the 9 grafts had to be removed. The finding that plasma
      concentrations of prothrombin fragment 1 and 2 were higher 4 h after the first
      OKT3 dose in OKT3 recipients than in transplant patients who received other
      prophylaxis (mean 5.88 [SEM 0.76] vs 2.25 [0.59] nmol/l, p less than 0.01)
      confirms that OKT3 has procoagulant effects in vivo.

PMID- 1347806
TI  - Enzymes as autoantigens.

PMID- 1347807
TI  - Streptokinase plus aspirin does the trick: ISIS-3.

PMID- 1347808
TI  - Splenic autotransplantation.

PMID- 1347809
TI  - Pandora's angina.

PMID- 1347810
TI  - Does infection occur with modern intrauterine devices?

PMID- 1347811
TI  - Protecting individuals; preserving data.

PMID- 1347813
TI  - Magnetic resonance angiography of renal transplants.
AB  - Stenosis of the artery of transplanted kidneys is an important cause of graft
      dysfunction. Diagnosis and follow-up of this condition normally requires intra
      arterial digital-subtraction angiography (IADSA), which is invasive and may cause
      complications. A possible alternative to IADSA is magnetic resonance angiography
      (MRA), and we have assessed this technique in 50 renal transplant patients who
      were referred for investigation of possible renal arterial stenosis. In every
      patient, MRA was compared prospectively with conventional IADSA. Compared with
      IADSA, MRA had a sensitivity of 83% and a specificity of 97%, and when all images
      were graded retrospectively for severity of stenosis, the two techniques showed a
      significant correlation (r = 0.74, p less than 0.001). MRA can provide an
      accurate image of the renal transplant artery in a non-invasive manner with a
      high sensitivity and specificity.

PMID- 1347812
TI  - Intrauterine devices and pelvic inflammatory disease: an international
      perspective.
AB  - The risk of pelvic inflammatory disease (PID) associated with use of an
      intrauterine device (IUD) has been an important concern that has dominated
      decisions on its use throughout the world, especially in the USA. Early research
      that suggested such an association led to both a dramatic decline in use of the
      method and its withdrawal from the US market by two manufacturers. However,
      factors other than use of an IUD are now thought to be major determinants of PID
      risk. To address these concerns, we have reviewed the World Health Organisation's
      IUD clinical trial data to explore the incidence and patterns of PID risk with
      use of an IUD. The overall rate of PID among 22,908 IUD insertions and during
      51,399 woman-years of follow-up was 1.6 cases per 1000 woman-years of use. After
      adjustment for confounding factors, PID risk was more than six times higher
      during the 20 days after insertion than during later times (unadjusted rates, 9.7
      vs 1.4 per 1000 woman-years, respectively); the risk was low and constant for up
      to eight years of follow-up. Rates varied according to geographical area (highest
      in Africa and lowest in China) and were inversely associated with age. PID rates
      were lower among women who had IUDs inserted more recently. Our findings indicate
      that PID among IUD users is most strongly related to the insertion process and to
      background risk of sexually transmissible disease. PID is an infrequent event
      beyond the first 20 days after insertion. Because of this increased risk with
      insertion, IUDs should be left in place up to their maximum lifespan and should
      not routinely be replaced earlier, provided there are no contraindications to
      continued use and the woman wishes to continue with the device.

PMID- 1347814
TI  - Stroke: rehabilitation and long-term care.

PMID- 1347815
TI  - Stroke services.

PMID- 1347816
TI  - The poor need no more charlatans.

PMID- 1347817
TI  - Retractor design and the lingual nerve.

PMID- 1347818
TI  - Viral hepatitis.

PMID- 1347819
TI  - CGVD workshop: should Haemophilus influenzae type B conjugate vaccines be
      introduced into the EPI?

PMID- 1347820
TI  - HIV, AIDS, and zidovudine.

PMID- 1347821
TI  - HIV, AIDS, and zidovudine.

PMID- 1347822
TI  - Didanosine and heart failure.

PMID- 1347823
TI  - Wound dressings and airborne dispersal of bacteria.

PMID- 1347824
TI  - Dilutional hyponatraemia.

PMID- 1347825
TI  - Dilutional hyponatraemia.

PMID- 1347826
TI  - HCV genotypes in different countries.

PMID- 1347827
TI  - Psychotic reactions to zolpidem.

PMID- 1347828
TI  - Rabies virus, paralytic and classical.

PMID- 1347829
TI  - Retrograde acute lymphangiitis.

PMID- 1347830
TI  - Natural history of breast cancer.

PMID- 1347831
TI  - Natural history of breast cancer.

PMID- 1347832
TI  - Natural history of breast cancer.

PMID- 1347833
TI  - Cholesterol-lowering drugs in familial defective apolipoprotein B-100.

PMID- 1347834
TI  - Photoablation of oocyte zona pellucida by erbium-YAG laser for in-vitro
      fertilisation in severe male infertility.

PMID- 1347835
TI  - Promoting safe motherhood.

PMID- 1347836
TI  - Promoting safe motherhood.

PMID- 1347837
TI  - UK parliamentary report of maternity services.

PMID- 1347838
TI  - Finnish survey of public opinion about public expenditure.

PMID- 1347839
TI  - Publicity and unpublished results.

PMID- 1347840
TI  - Serious intercurrent disease in healthy volunteers in clinical pharmacological
      research.

PMID- 1347841
TI  - Day care and pregnancy hypertension.

PMID- 1347842
TI  - Worldwide worsening wheezing--is the cure the cause?

PMID- 1347843
TI  - Dependence and oestrogen replacement.

PMID- 1347844
TI  - Bjork-Shiley valves.

PMID- 1347845
TI  - Stridor and focal laryngeal dystonia.

PMID- 1347846
TI  - Pruritus after cardiopulmonary bypass.

PMID- 1347848
TI  - Thrombolysis and risk of intracranial bleeding.

PMID- 1347847
TI  - Painless blood sampling for self blood glucose measurement.

PMID- 1347849
TI  - Hepatocyte growth factor concentrations after liver resection.

PMID- 1347850
TI  - Vancomycin resistance in south London.

PMID- 1347851
TI  - Outbreak of hepatitis A among Italian patients with haemophilia.

PMID- 1347852
TI  - Hypomelanosis of Ito.

PMID- 1347853
TI  - Colorectal and anal motility during defaecation.

PMID- 1347854
TI  - Randomised trial of artesunate and mefloquine alone and in sequence for acute
      uncomplicated falciparum malaria.
AB  - The increasing frequency of therapeutic failures in falciparum malaria in
      Thailand shows an urgent need for effective drugs or drug combinations.
      Artesunate, a qinghaosu derivative, is effective in clearing parasitaemia
      rapidly, but the recrudescence rate can be as high as 50%. We have compared
      artesunate followed by mefloquine with each drug alone in acute, uncomplicated
      falciparum malaria. 127 patients were randomly assigned treatment with artesunate
      (600 mg over 5 days), mefloquine (750 mg then 500 mg 6 h later), or artesunate
      followed by mefloquine. All patients were admitted to hospital for 28 days to
      exclude reinfection. Cure was defined as no recrudescence during the 28 days'
      follow-up. The cure rates for mefloquine and artesunate alone were 81% (30/37
      patients) and 88% (35/40); the combination was effective in all of 39 patients.
      Fever and parasite clearance times were significantly shorter in the groups that
      received artesunate than in the mefloquine-only group. The frequency of nausea
      and vomiting was slightly, but not significantly, higher among patients who
      received both drugs than in the other groups. The combination of artesunate
      followed by mefloquine is highly effective and well tolerated in patients with
      acute, uncomplicated falciparum malaria in Thailand.

PMID- 1347855
TI  - T-cell receptor variable gene products and early HIV-1 infection.
AB  - To assess the hypothesis that the human immunodeficiency virus (HIV) might mimic
      major histocompatibility complex (MHC) allodeterminants and interact with T-cell
      receptors (TCRs) of alloreactive T-cells, we have done a preliminary analysis of
      the range of alpha beta TCR gene products in 16 HIV-1-seropositive individuals
      with normal CD4 counts and in 16 healthy HIV-1-negative controls. Using a panel
      of monoclonal antibodies with a two-colour direct immunofluorescence method, we
      found a significant increase in the expression of the V beta 5.3 subfamily in the
      HIV-positive patient group compared with controls (p less than 0.01). Selected
      increase in expression of V beta sequences has been described in various
      autoimmune conditions and our findings raise the possibility that the
      immunopathological damage from HIV infection may be due to the induction of
      autoreactivity. If HIV does mimic MHC II, the normal immune response to the virus
      could represent an autoimmune process similar to graft-versus-host disease.

PMID- 1347856
TI  - Conservative treatment of mild/moderate cervical dyskaryosis: long-term outcome.
AB  - There is some controversy about the management of women with mild or moderate
      dyskaryotic cervical smears. To assess the strategy of an established cervical
      cytology screening programme (Grampian region, northeast Scotland) we identified
      500 women who had had mild or moderate cervical dyskaryosis in 1978 or 1979, and
      500, matched by age, who had had a normal smear at that time. Follow-up smear
      results and any subsequent investigation by colposcopy, cone biopsy, or
      hysterectomy, with biopsy result were recorded. Of the 500 women who initially
      had an abnormal smear, 300 (60%) had a smear that was normal or inflammatory at
      their last visit (after seven years' median follow-up). 184 (37%) had undergone
      biopsy, 97 (19%) of whom were cervical intraepithelial neoplasia grade III or
      worse. Survival curves for time to biopsy and ten-year biopsy rates show that
      women with an abnormal smear before their baseline year were the most likely to
      have a subsequent biopsy. Older women had a biopsy less often and at biopsy were
      more likely to have minor abnormalities. Mild or moderate dyskaryotic smears
      should not be an indication for immediate referral for colposcopy, since under a
      conservative management policy most women return to normal without needing
      treatment. Nevertheless, the increased risk associated with abnormal smears
      justifies rigorous surveillance.

PMID- 1347857
TI  - Effect of calcitonin-gene-related peptide in patients with delayed postoperative
      cerebral ischaemia after aneurysmal subarachnoid haemorrhage. European CGRP in
      Subarachnoid Haemorrhage Study Group.
AB  - The finding that the carotid vascular beds are sensitive to the potent
      vasodilator calcitonin-gene-related peptide (CGRP) suggested that the drug might
      help to prevent ischaemic deterioration after surgery for aneurysmal subarachnoid
      haemorrhage (SAH). The results of a preliminary study were encouraging, so we
      have carried out a randomised multicentre single-blind comparison of CGRP and
      standard best management in patients with ischaemic deficits after surgery for
      ruptured intracranial aneurysms. Patients aged 18-70 years in whom a focal
      neurological deficit developed or who had a reduction of 2 or more points on the
      Glasgow coma scale (GCS) after surgery entered the study after computed
      tomography had excluded non-ischaemic causes for the neurological deficit. 62
      patients were randomly assigned an infusion of 0.6 micrograms/min CGRP for 4 h,
      then up to a maximum of 10 days, and 55 patients standard best management
      (controls). GCS and haemodynamic variables were assessed during the hospital
      stay, and all patients were followed up at 3 months by an independent
      investigator, who was unaware of their treatment. Outcome, measured on the
      Glasgow outcome scale, at 3 months was good in 66% of those treated with CGRP and
      60% in the controls; the relative risk of a poor outcome in CGRP-treated patients
      was 0.88 (95% confidence interval 0.60 to 1.28). Hypotension was a common side
      effect of the CGRP infusion. 66% of the CGRP group did not complete treatment
      because of adverse events (19 patients), lack of improvement at 4 h (17 patients)
      or later (4 patients), or patient's request (1 patient). Although we could not
      show a significant beneficial effect of CGRP in this trial, the wide confidence
      interval for the risk of a poor outcome and the fact that only a third of
      patients completed treatment mean that a clinically useful benefit cannot yet be
      ruled out.

PMID- 1347858
TI  - High incidence of primary gastric lymphoma in northeastern Italy.
AB  - We previously noted an extraordinarily high number of cases of primary gastric
      lymphoma (PGL) in northeastern Italy. We have now formally compared the incidence
      in Feltre, Italy, with that in three similar communities in the UK. Each
      community has a stable population served by a single endoscopy unit and
      histopathology laboratory. There were 13 times more cases of PGL in Feltre in
      1986-91 than in the UK communities (66 vs 5 per 100,000 per 5 years). The
      incidence of gastric adenocarcinoma was also substantially higher in Feltre than
      in the UK (270 vs an average of 82 per 100,000 per 5 years), as was the
      prevalence of gastritis associated with Helicobacter pylori infection (87% of
      1343 gastric biopsy samples in 1991).

PMID- 1347859
TI  - Urinary excretion of platelet-activating factor in haemolytic uraemic syndrome.
AB  - Since some of the features of haemolytic uraemic syndrome (HUS), such as platelet
      activation and glomerular injury, could be brought about by platelet-activating
      factor (PAF), we have studied the urinary excretion of PAF in 10 children with
      HUS and in 10 healthy age-matched controls. Urinary PAF concentrations, measured
      by radioimmunoassay, were significantly higher in acute-phase HUS patients than
      in controls (mean 2.04 [SD 1.66] vs 0.72 [0.43] ng/mg creatinine, p less than
      0.05) but were similar to those in controls in samples taken after recovery. High
      PAF concentrations during the acute phase of HUS may reflect platelet activation
      and glomerular injury; the lower values after recovery suggest that urinary PAF
      may be a marker of disease activity.

PMID- 1347860
TI  - Octreotide steaming ahead.

PMID- 1347862
TI  - The Helicobacter genus: now we are nine.

PMID- 1347861
TI  - AIDS: how can a pussy cat kill?

PMID- 1347863
TI  - Warm heart surgery.

PMID- 1347864
TI  - Biology of small-cell lung cancer.

PMID- 1347865
TI  - Management of small-cell cancer of the lung.

PMID- 1347866
TI  - Effects of increased inspired oxygen concentrations on exercise performance in
      chronic heart failure.
AB  - Exercise capacity in patients with stable heart failure may be influenced by
      prolonged drug treatment or exercise training, but acute interventions are
      generally thought to have little effect. Cardiorespiratory responses to exercise
      were studied in 12 consecutive patients with chronic congestive heart failure who
      underwent serial submaximal and maximal exercise tests at inspired oxygen
      concentrations of 21% (room air), 30%, and 50%. Mean (SD) exercise duration
      during progressive testing to maximum exercise capacity was prolonged from 548
      (276) s on room air to 632 (285) s on 50% oxygen (p = 0.012). During steady-state
      exercise at 45 W, oxygen enrichment to 50% was associated with significantly
      increased arterial oxygen saturation (94.6 [1.9]% to 97.5 [1.3]%), and
      significantly reduced minute ventilation (36.1 [8.6] l/min to 28.1 [5.9] l/min),
      cardiac output (7.5 [2.3] l/min to 6.5 [1.9] l/min), and subjective scores for
      fatigue and breathlessness (13.9 [3.1] to 11.5 [3.5]) compared with room air
      intermediate changes were observed with 30% inspired oxygen. Increased inspired
      oxygen concentrations can improve exercise performance acutely and modify the
      ventilatory response to exercise in patients with heart failure. Hyperoxia
      reduces ventilatory response and circulatory demand while maintaining oxygen
      delivery at a given workload. The potential benefits of increased inspired oxygen
      concentrations in the treatment of chronic heart failure merit further
      assessment.

PMID- 1347867
TI  - Incidence of cancers of the larynx and lung near incinerators of waste solvents
      and oils in Great Britain.
AB  - The Small Area Health Statistics Unit (SAHSU) is a new independent facility for
      the investigation of disease near industrial installations in the UK. SAHSU
      analysed the incidence of cancers of the larynx and lung near the incinerator of
      waste solvents and oils at Charnock Richard, Coppull, Lancashire (which operated
      between 1972 and 1980) and nine other similar incinerators in Great Britain,
      after reports of a cluster of cases of cancer of the larynx near the Charnock
      Richard site. Postcoded cancer registration data were available for 1974-84 in
      England and Wales and 1975-87 in Scotland. Lag periods of 5 and 10 years were
      used between start-up (or first registration) of the incinerators and cancer
      incidence. Standardised observed/expected (O/E) ratios were assessed within 3 km
      and 3-10 km of each site and then aggregated over all sites. Expected values were
      based on national rates (regionally adjusted) with and without stratification by
      Carstairs' index, a measure of the socioeconomic profile of areas that uses
      census data for enumeration districts. Data were also assessed over a range of
      circles up to 10 km to test for trend in O/E ratios with distance. For Charnock
      Richard, none of the O/E ratios within 3 km or from 3-10 km differed
      significantly from unity, for either cancer or lag period. In the analysis of all
      sites with stratification by Carstairs' index, none of these O/E ratios differed
      significantly from unity for the two cancers. There was no evidence of decreasing
      risk with distance from the sites of either cancer. We conclude that the apparent
      cluster of cases of cancer of the larynx reported near Charnock Richard was
      unlikely to be due to its former incinerator.

PMID- 1347868
TI  - Eye monitoring in diabetes.

PMID- 1347869
TI  - Origin of AIDS.

PMID- 1347870
TI  - Origin of AIDS.

PMID- 1347871
TI  - Origin of AIDS.

PMID- 1347872
TI  - Kaposi's sarcoma and disseminated tuberculosis in HIV-negative individual.

PMID- 1347873
TI  - Local anaesthesia to prevent post-laparoscopic shoulder pain.

PMID- 1347874
TI  - Lithium and pregnancy.

PMID- 1347875
TI  - Transcutaneous ultrasound measurement of flow in internal mammary artery.

PMID- 1347876
TI  - Colorectal cancer and dietary intervention.

PMID- 1347877
TI  - "Wearing-off" and beta 2-adrenoceptor agonist in Parkinson's disease.

PMID- 1347878
TI  - Acid-base disturbances and heat-stress in the armed forces.

PMID- 1347879
TI  - Anti-HCV, anti-GOR, and autoimmunity.

PMID- 1347880
TI  - Anti-HCV, anti-GOR, and autoimmunity.

PMID- 1347881
TI  - Fractals and ophthalmology.

PMID- 1347883
TI  - Cyclosporin and asthma.

PMID- 1347882
TI  - Cyclosporin and asthma.

PMID- 1347884
TI  - Reversal of graft rejection with monoclonal anti-interleukin-2 receptor.

PMID- 1347885
TI  - Electronic influenza surveillance.

PMID- 1347886
TI  - Epoetin and the right to prescribe.

PMID- 1347887
TI  - Drug regulation in Pakistan.

PMID- 1347888
TI  - Research in developing countries.

PMID- 1347889
TI  - Hazards of clinical trials.

PMID- 1347890
TI  - Proof of causation.

PMID- 1347891
TI  - Chorionic villus sampling and limb abnormalities. The EUROCAT Working Group.

PMID- 1347892
TI  - Cardiogenic embolism to the brain.

PMID- 1347893
TI  - Customised antenatal growth charts.

PMID- 1347894
TI  - Customised antenatal growth charts.

PMID- 1347895
TI  - Customised antenatal growth charts.

PMID- 1347896
TI  - Magnetic resonance studies in stroke.

PMID- 1347897
TI  - Blood donors and autoimmunity.

PMID- 1347898
TI  - Glutaraldehyde allergy in hospital workers.

PMID- 1347899
TI  - Potential dangers of laparoscopic insufflator.

PMID- 1347900
TI  - p53 codon 249ser mutations in hepatocellular carcinoma patients with low
      aflatoxin exposure.

PMID- 1347901
TI  - Chronic exposure to ozone and respiratory health of children.

PMID- 1347902
TI  - ELISA for diagnosis of acute sporadic hepatitis E.

PMID- 1347903
TI  - Indomethacin and postprandial gallbladder emptying.

PMID- 1347904
TI  - Effects of passive immunization of growth hormone-releasing hormone and
      somatostatin on growth hormone secretion under conditions of high somatostatin
      tone.
AB  - Pulsatile GH secretion decreases during food-deprivation in the rat. It has been
      hypothesized that this decrease is due to elevated hypothalamic somatostatin
      secretion. This is based on the observation that GH increases in food-deprived
      rats following removal of endogenous somatostatin using passive immunization
      techniques. Cognizant of the important stimulatory effects of growth hormone
      releasing hormone (GHRH) on GH secretion, we sought to determine if this
      neuropeptide plays any role in mediating GH secretion in food-deprived rats. Male
      rats were prepared with indwelling venous catheters using sodium pentobarbital
      anesthesia seven days prior to experimentation. Animals were food-deprived for 72
      h, after which control blood samples were drawn from -60 to 0 min. One group was
      then treated with normal rabbit serum (NRS), while a second group was treated
      with GHRH antiserum (GHRHab). At 55 min all animals received somatostatin
      antiserum (SSab). No animal exhibited any spontaneous GH peak during the one hour
      control period or in the subsequent one hour period following the administration
      of GHRHab or NRS. Absence of GH pulsatility during food-deprivation, coupled with
      no decrease in GH levels in food-deprived rats treated with GHRHab suggest that
      diminished GHRH pulsatility is likely during food-deprivation. Subsequent
      treatment of these animals with SSab resulted in an identical 2.5 fold increase
      in GH concentrations. This result suggests that GHRH is not involved in the GH
      rebound following somatostatin withdrawal in food-deprived rats.

PMID- 1347905
TI  - Drugs affecting microtubule dynamics increase alpha-tubulin mRNA accumulation via
      transcription in Tetrahymena thermophila.
AB  - In cultured mammalian cells, an increase in the amount of tubulin monomer due to
      treatment with a microtubule-depolymerizing agent results in a rapid decline in
      tubulin synthesis. This autoregulatory response is mediated through a
      posttranscriptional mechanism which decreases the stability of tubulin message
      with no change in transcriptional activity of tubulin genes. Conversely,
      treatment with a microtubule-polymerizing drug, such as taxol, results in a
      slight increase in the synthesis of tubulin. Surprisingly, we find that two
      microtubule-depolymerizing agents, colchicine and oryzalin, actually cause an
      increase in alpha-tubulin synthesis and alpha-tubulin message in starved
      Tetrahymena thermophila. This increase is paralleled by an increase in
      transcription of alpha-tubulin sequences measured by run-on transcription, while
      the half-life of tubulin message measured by decay in the presence of actinomycin
      D does not change appreciably. Treatment of starved cells with taxol also
      produces an increase in alpha-tubulin synthesis via an increase in message
      abundance due to an increase in transcription of the alpha-tubulin gene. These
      results indicate that tubulin synthesis in T. thermophila is regulated very
      differently than in cultured mammalian cells.

PMID- 1347907
TI  - The effects on survival of early treatment of human immunodeficiency virus
      infection.
AB  - BACKGROUND: Zidovudine has been shown to prolong survival in patients with the
      acquired immunodeficiency syndrome (AIDS) and, in persons with human
      immunodeficiency virus (HIV) infection but not AIDS, to delay the progression to
      AIDS. However, it is still uncertain whether treatment before the development of
      AIDS prolongs survival. METHODS: We analyzed data from a cohort of 2162 high-risk
      men who were already seropositive for HIV type 1 (HIV-1) and 406 men who
      seroconverted from October 1986 through April 1991. There were 306 deaths. The
      probabilities of death were compared among men at similar stages of disease who
      began zidovudine therapy before the diagnosis of AIDS and among those who did
      not. Relative risks of death were calculated for each of five initial disease
      states on the basis of CD4+ cell counts and clinical symptoms and signs appearing
      over follow-up periods of 6, 12, 18, and 24 months. Adjustments were also made
      for the use of prophylaxis against Pneumocystis carinii pneumonia (PCP). RESULTS:
      After we controlled for CD4+ cell count and symptoms, the use of zidovudine with
      or without PCP prophylaxis before the development of AIDS significantly reduced
      mortality in all follow-up periods. The relative risks of death were 0.43 (95
      percent confidence interval, 0.23 to 0.78) at 6 months, 0.54 (95 percent
      confidence interval, 0.38 to 0.78) at 12 months, 0.59 (95 percent confidence
      interval, 0.44 to 0.79) at 18 months, and 0.67 (95 percent confidence interval,
      0.52 to 0.86) at 24 months. After we adjusted for the effects of PCP prophylaxis,
      zidovudine alone significantly reduced mortality at 6, 12, and 18 months
      (relative risks, 0.45, 0.59, and 0.70, respectively), but not at 24 months
      (relative risk, 0.81). Among zidovudine users, those who also used PCP
      prophylaxis before the development of AIDS had significantly lower mortality at
      18 and 24 months than those who did not (relative risks, 0.62 and 0.60,
      respectively). CONCLUSIONS: The results of this study support the hypothesis that
      in HIV-1 infection, early treatment with zidovudine and PCP prophylaxis improves
      survival in addition to slowing the progression to AIDS.

PMID- 1347908
TI  - The rationale for continuous dopaminergic stimulation in patients with
      Parkinson's disease.
AB  - Continuous dopaminergic stimulation has been shown to stabilize motor
      fluctuations in patients with advanced Parkinson's disease (PD) who do not
      respond to more conventional forms of therapy. Levodopa infusions confer
      immediate benefit as a direct result of maintaining steady plasma levodopa
      concentrations. Fluctuations of synaptic dopamine inherent in the usual oral
      treatment of PD might result in deleterious postsynaptic changes. Some of these
      presumed receptor alterations might revert as a consequence of continuous
      levodopa infusion.

PMID- 1347906
TI  - Expression of the CD4 gene requires a Myb transcription factor.
AB  - We have analyzed the control of developmental expression of the CD4 gene, which
      encodes an important recognition molecule and differentiation antigen on T cells.
      We have determined that the CD4 promoter alone functions at high levels in the
      CD4+ CD8- mature T cell but not at the early CD4+ CD8+ stage of T-cell
      development. In addition, the CD4 promoter functions only in T lymphocytes; thus,
      the stage and tissue specificity of the CD4 gene is mediated in part by its
      promoter. We have determined that a Myb transcription factor binds to the CD4
      promoter and is critical for full promoter function. Thus, Myb plays an important
      role in the expression of T-cell-specific developmentally regulated genes.

PMID- 1347909
TI  - Initiating treatment of Parkinson's disease.
AB  - Treatment of Parkinson's disease (PD) can be divided into two categories:
      symptomatic therapy (restoring dopamine levels toward normal and reversing
      functional disability) and preventive therapy (interfering with the
      pathophysiologic mechanism of PD to prevent or decrease the rate of progression
      of the disease). Regarding symptomatic treatment, although anticholinergic
      preparations generally are considered effective for the symptoms of tremor and
      rigidity without altering bradykinesia, their effectiveness is limited and
      adverse reactions are common; their role should be restricted to use as adjuvants
      to levodopa therapy. Amantadine has been shown to be as effective as
      anticholinergics, but it lacks long-term efficacy. Dopamine agonists-
      bromocriptine, pergolide mesylate and lisuride in Europe--are not as effective as
      levodopa and therefore rarely are used as initial therapy; their proposed role,
      too, is as adjuvants to levodopa therapy. Levodopa is the most effective drug
      presently available for the treatment of PD; its introduction is accompanied by
      rapid and dramatic reduction of symptoms and signs. Initial adverse reactions are
      not usually a major problem; and although there is speculation that initiation of
      therapy should be delayed because of possible long-term complications, clinically
      distinguishing these from problems related to disease progression itself is
      difficult. The possibility that nigral cell death is mediated by oxidative
      mechanisms provides the basis for considering antioxidant therapy as protective
      treatment; selegiline, an antioxidant, has been found to delay the need for
      symptomatic therapy. It is suggested that initial treatment of Parkinson's
      disease begin with both preventive therapy with selegiline and symptomatic
      treatment with the sustained-release preparation of levodopa, which may be
      associated with fewer long-term complications.

PMID- 1347910
TI  - Fatal familial insomnia: a second kindred with mutation of prion protein gene at
      codon 178.
AB  - Fatal familial insomnia (FFI), a condition characterized by inability to sleep,
      dysautonomia, motor disturbances, and selective thalamic atrophy is a prion
      disease linked to a GAC----AAC mutation at codon 178 of the prion gene. These
      data were obtained from one kindred. We now report a second kindred affected by
      FFI and carrying the same mutation. The finding of the same disease phenotype and
      genotype in a second family further validates FFI as a distinct disease entity
      and a phenotype of the GAC----AAC mutation at codon 178 of the prion gene.

PMID- 1347912
TI  - The provision of oral healthcare for patients with HIV disease. Proceedings of
      workshop. London, Ontario, Canada, October 11-12, 1990.

PMID- 1347911
TI  - Somatostatin analog in managing postgastrectomy duodenal stump leak.
AB  - Somatostatin and its long-acting analog have a host of activities and potential
      applications in medicine today. Somatostatin is a naturally occurring peptide
      containing 14 amino acids. The following is one example of the many uses of
      somatostatin in the surgical patient.

PMID- 1347913
TI  - The v-erbA oncogene requires cooperation with tyrosine kinases to arrest
      erythroid differentiation induced by ligand-activated endogenous c-erbA and
      retinoic acid receptor.
AB  - The v-erbA oncogene, a mutated version of the thyroid hormone receptor alpha (c
      erbA/TR-alpha), cooperates with tyrosine kinase oncogenes in erythroblast
      transformation. Here we show that the ligand-activated, endogenous retinoic acid
      receptor (RAR-alpha), in cooperation with c-erbA/TR-alpha, efficiently reverses
      the transforming effect of kinase oncogenes, overcoming oncogene-induced self
      renewal by triggering terminal differentiation of the transformed cells into
      healthy erythrocytes. This differentiation induction was accompanied by up
      regulation of erythrocyte gene expression. Similarly, RAR-alpha and over
      expressed exogenous c-erbA/TR-alpha efficiently abolished the differentiation
      arrest caused by v-erbA, while the low levels of endogenous TR-alpha had no
      effect. In contrast, transformation by v-erbA plus a kinase oncogene was not
      affected at all by ligand-activated endogenous or over-expressed exogenous TR
      alpha and RAR-alpha. These results suggest that oncogene cooperation is required
      to protect leukemic erythroblasts from differentiation induction via endogenous,
      nuclear hormone receptors. Endogenous c-erbA/TR-alpha and RAR-alpha apparently
      cooperated in abolishing erythroblast self-renewal and inducing differentiation,
      since the respective ligands acted in a synergistic fashion, and overexpressed,
      non-ligand-bound c-erbA/TR-alpha suppressed endogenous RAR-alpha function in
      differentiation induction. Genetic evidence is presented that this functional
      cooperation requires the receptor dimerization domain, suggesting that TR
      alpha/RAR-alpha heterodimers play a role in regulation of erythroid
      differentiation.

PMID- 1347914
TI  - Modulation of normal erythroid differentiation by the endogenous thyroid hormone
      and retinoic acid receptors: a possible target for v-erbA oncogene action.
AB  - The v-erbA oncogene, a mutated version of the thyroid hormone receptor alpha (c
      erbA/TR-alpha), inhibits erythroid differentiation and constitutively represses
      transcription of certain erythrocyte genes, suggesting a normal function of the
      proto-oncogene c-erbA in erythropoiesis. Here we demonstrate that the endogenous
      thyroid hormone receptor alpha (c-erbA/TR-alpha) and the closely related retinoic
      acid receptor alpha (RAR-alpha) play a role in the regulation of normal erythroid
      differentiation. Retinoic acid (RA) distinctly modulated the erythroid
      differentiation program of normal erythroid progenitors and erythroblasts
      reversibly transformed by a conditional tyrosine kinase oncogene. When added
      pulsewise to immature cells, differentiation was accelerated while more mature
      cells underwent premature cell death. Thyroid hormone (T3) alone caused similar
      but weaker effects. Interestingly, T3 strongly enhanced the action of RA,
      suggesting cooperative action of the two receptors in modulating erythroid
      differentiation. Expression of the human RAR-alpha in receptor-negative
      erythroblasts conferred RA-induced regulation of differentiation to the otherwise
      unresponsive cells, thus showing that the RAR-alpha is essential for the RA
      effect. Likewise, enhanced expression of exogenous c-erbA/TR-alpha in
      erythroblasts rendered them susceptible to modulation of differentiation by T3,
      suggesting a similar function of both receptors.

PMID- 1347915
TI  - Increased expression of genes from growth factor signaling pathways in
      glioblastoma cell lines.
AB  - The concept of autocrine stimulation of cell proliferation postulates growth
      autonomy by acquisition of the ability to produce and respond to growth factors.
      Overproduction of several growth factors in a variety of human tumors and cell
      lines derived from these tumors has been reported. We have screened several cell
      lines derived from glioblastomas for anomalies in the expression of genes
      encoding transforming growth factor alpha (TGF-alpha), TGF-beta, basic fibroblast
      growth factor (bFGF) and its high-affinity receptor, flg. Compared with normal
      human brain tissue, we observed a generalized elevation in the levels of
      expression of these genes in glioblastoma cell lines and an SV40-transformed
      human astroglial cell line. Overexpression of these genes does not appear to be
      merely a reflection of the proliferative state of transformed cells since some
      other human tumor cell lines, when analysed for the expression of TGF-beta and
      bFGF, did not show a significant increase in these transcripts. The specificity
      of the elevated transcription of TGF-alpha, TGF-beta, bFGF and flg in
      glioblastoma cell lines is further suggested by the fact that the transcription
      of the proto-oncogene c-erbB2, which is overproduced in breast tumor cell lines,
      was not elevated in glioblastoma cell lines. Increased expression of growth
      factors, which are potent mitogens and angiogens, and/or their receptors may have
      critical roles in autonomous proliferation as well as neovascularization of
      glioblastomas.

PMID- 1347916
TI  - Three distinct regions involved in 3p deletion in human lung cancer.
AB  - The 3p deletion was first noted by cytogenetic analysis and was later confirmed
      by several independent studies using restriction fragment length polymorphism
      (RFLP) probes. As an initial step towards positional cloning (reverse genetics)
      of the tumor-suppressor gene(s) on 3p, a detailed analysis of the minimum deleted
      region(s) on 3p was performed with 13 RFLP probes and 48 paired human lung cancer
      samples. All nine small-cell lung cancer cases (100%) and 31 of 39 non-small-cell
      lung cancer cases (79%) showed allelic loss at one or more loci mapped on 3p. We
      show here that three distinct regions on 3p appear to be frequently deleted in
      lung cancer. These regions include 3p25, 3p21.3 and 3p14-cen. The present study
      should warrant future work focusing on these chromosomal regions on 3p, and may
      ultimately lead to the isolation of tumor-suppressor genes involved in the
      pathogenesis of lung cancer.

PMID- 1347917
TI  - Surface expression of erbB-2 protein is post-transcriptionally regulated in
      mammary epithelial cells by epidermal growth factor and by the culture density.
AB  - The control of expression of the erbB-2 protein was examined in two mammary
      epithelial cells lines, HC11 and 31E. The erbB-2 protein content varied
      dramatically depending upon cell density and upon the presence of epidermal
      growth factor (EGF) in the culture medium. The changes in protein content were
      not due to variation in the erbB-2 mRNA level. Analysis of the metabolic turnover
      of the erbB-2 protein showed that its rate of degradation was two- to threefold
      higher in cells growing at low density than in cells confluent for 2 days. The
      addition of EGF to the culture medium caused an increase in the phosphoamino acid
      content and an increase in the turnover of the erbB-2 protein. Cell fractionation
      experiments were performed, and a shift in the cellular localization of the erbB
      2 protein towards the lysosomal compartment in EGF-treated HC11 cells was found.
      This is reflected by an increase in the degradation rate of the erbB-2 protein.
      These findings suggest that in mammary epithelial cells the stability of the erbB
      2 protein is an important regulatory control point in determining the level of
      the protein. The degradation rate is sensitive to cell confluency and is
      controlled by EGF receptor activity.

PMID- 1347918
TI  - Scc-1, a novel colon cancer susceptibility gene in the mouse: linkage to CD44 (Ly
      24, Pgp-1) on chromosome 2.
AB  - Mutations of proto-oncogenes and tumor-suppressor genes lead to neoplastic
      development. Some germline mutations of these genes increase the tumor
      susceptibility of their carriers, but the relationship between genes controlling
      tumor susceptibility and the known oncogenes and tumor-suppressor genes remains
      unelucidated. Moreover, as tumor susceptibility in mouse is controlled by
      multiple genes, their identification has been virtually impossible. We therefore
      developed a new system, the recombinant congenic strains (RCS), which separates
      individual susceptibility genes into different RC strains, thus facilitating
      their analysis. To map genes controlling the development of colon cancer, we used
      the Balb/c-c-STS (CcS/Dem) RC strains. Owing to several unidentified genes,
      Balb/cHeA mice are relatively resistant and STS/A mice highly susceptible to 1,2
      dimethylhydrazine-(DMH)-induced colon adenocarcinomas. Each CcS/Dem strain
      carries a different subset of about 12.5% of genes of the STS strain on the
      Balb/c background, and individual STS susceptibility genes became segregated into
      different RC strains. Using CcS-19, one of the highly susceptible RC strains, we
      mapped a novel colon tumor susceptibility gene, Scc-1, different from the
      oncogenes and tumor-suppressor genes known to be involved in colon tumorigenesis,
      in the vicinity of CD44 (Ly-24, Pgp-1) on chromosome 2. The mapping of the Scc-1
      gene indicates that the RCS system can be used to map and study the presently
      unknown genes which control cancer development.

PMID- 1347919
TI  - The nuclear oncogenes v-erbA and v-ets cooperate in the induction of avian
      erythroleukemia.
AB  - The nuclear oncogenes v-erbA and v-ets are known to cooperate with other viral
      oncogenes in the induction of avian erythroleukemia. Thus, in the case of avian
      erythroblastosis virus (AEV), v-erbA enhances the effect of the tyrosine kinase
      encoding v-erbB oncogene by blocking the terminal differentiation of erythroid
      cells. In the case of E26 virus a fusion of the product from v-ets to that of the
      nuclear oncogene v-myb is a prerequisite for leukemogenicity. Here we show that
      an artificial virus carrying both v-erbA and v-ets induces a rapid, acute
      erythroleukemia phenotypically similar to that induced by AEV. In contrast, virus
      constructs containing either v-erbA or v-ets alone are non-leukemogenic, although
      they are capable of transforming erythroid cells in vitro. Analysis of in vitro
      transformed cells showed that v-erbA induces a block of differentiation without
      abrogating dependence on anemic serum, while v-ets predominantly causes anemic
      serum independence. As expected, cells transformed by both oncogenes exhibit an
      increased proliferative potential, are blocked in differentiation and are anemic
      serum independent. These data demonstrate that two separately expressed nuclear
      oncoproteins can complement each other in vitro and in vivo. They also show that
      the v-Ets protein on its own can contribute to leukemogenesis.

PMID- 1347920
TI  - [Alpha interferon treatment in hairy cell leukemia].
AB  - Since 1984 alpha-interferon (alpha IFN) has been the treatment of choice in cases
      of hairy-cell leukaemia. However, eight years' experience shows that, although a
      large majority of the patients are improved, they are not cured. Thus, a new type
      of cytostatic drug, perhaps capable of cure as well, may replace alpha-IFN for
      the treatment of hairy-cell leukaemia in the future.

PMID- 1347922
TI  - [Scandinavian Health Policy Forum. Many people needing care--family's role and
      society's responsibility].

PMID- 1347921
TI  - [Interferon treatment in neuroendocrine tumors].
AB  - Neuro-endocrine tumours of the abdomen have long constituted a therapeutic
      challenge. Although characterised by slow growth rates, these tumours produce
      peptides and amines which in turn give rise to more or less severe clinical
      symptoms. Surgery has been deemed the treatment of choice, and is to be
      considered even in cases of metastasising disease. Medical treatment includes
      chemotherapy, and treatment with somatostatin analogues and interferons. By means
      of long-term treatment with alpha-interferon (leukocyte interferon), the disease
      can be controlled for long periods.

PMID- 1347923
TI  - A new TaqI allele detected by the CRI-R227 (D4S101) probe in Pima Indians.

PMID- 1347924
TI  - PvuII RFLP in the cytovillin gene (VIL2) on human chromosome 6q.

PMID- 1347925
TI  - A new polymorphic probe on 5q11.2-13.3: ECB306Bg12.1 (D5S215).

PMID- 1347926
TI  - MaeIII polymorphism in sequence encoding 3' untranslated region of the MCC gene.

PMID- 1347927
TI  - AcyI-RFLP in intron 8 of hTPO gene.

PMID- 1347928
TI  - A hypervariable minisatellite locus D20S73 (pMS214.2) is located on 20q.

PMID- 1347929
TI  - Two hypervariable minisatellites D19S192 (pMS207.2) and D19S193 (pMS301.2)
      located at the distal ends of 19p and 19q respectively.

PMID- 1347930
TI  - A hypervariable locus D16S309 located at the distal end of 16p.

PMID- 1347931
TI  - A new RFLP marker D5S348 maps to 5p14.3-15.2, between D5S60 (CRI-R535) and
      HPRTP2.

PMID- 1347933
TI  - SphI RFLP at the human growth hormone gene cluster.

PMID- 1347932
TI  - A Hinf I polymorphism in the human elastin gene (ELN).

PMID- 1347934
TI  - A dinucleotide repeat polymorphism at the HOX2B locus.

PMID- 1347935
TI  - PCR detection of a BglII polymorphism in intron I of the human p53 gene (TP53).

PMID- 1347936
TI  - Pharmacologic treatment of attention deficit hyperactivity disorder.
AB  - This article describes the role of psychostimulant medication in the treatment of
      attention deficit hyperactivity disorder. Included are the drugs' putative
      mechanisms of action, pharmacology, toxicology, indications for their use, short
      term and long-term actions, adverse effects, specific dosing regimens,
      therapeutic monitoring techniques, alternative medications, and drug
      interactions.

PMID- 1347937
TI  - Schizophrenia.
AB  - Schizophrenia occurring in childhood and adolescence has similar diagnostic,
      prognostic, and treatment ramifications as those noted with adult-onset
      schizophrenia. In assessing a child or adolescent suspected of having
      schizophrenia, care must be given to document DSM-III-R diagnostic criteria
      within the developmental framework of the patient's functioning, while thoroughly
      evaluating for other potentially confounding disorders or conditions.
      Antipsychotic therapy is the only specific treatment for schizophrenia, and
      should be a fundamental component with a multimodal treatment program that also
      addresses the psychological, social, and educational needs of the patient and his
      or her family. Strategies for medication management vary depending on several
      factors, including the stage of the disorder, noted or potential side effects,
      and the response of the patient to treatment, and need to be coordinated for the
      long term by a child or adolescent psychiatrist familiar with the diagnosis and
      treatment of schizophrenia in this age group.

PMID- 1347938
TI  - The pharmacologic treatment of eating disorders.
AB  - There is substantial evidence that antidepressant medication is significantly
      superior to placebo in the short-term treatment of bulimia nervosa. Further work
      is needed to determine long-term outcome of patients with bulimia nervosa who
      receive antidepressant treatment, the role of antidepressants in patients who are
      receiving psychological treatment, and the utility of sequential medication
      trials. In the treatment of anorexia nervosa, there is little evidence that
      psychotropic medications, including antipsychotics, antidepressants, and
      cyproheptadine, are of significant benefit to most patients who are in the acute
      phase of treatment and are receiving behavioral treatment to promote weight gain.
      There is preliminary evidence that antidepressant medication, specifically
      fluoxetine, may be useful in preventing relapse in weight-recovered patients with
      anorexia nervosa, but this has not yet been documented in randomized, double
      blind, controlled trials.

PMID- 1347939
TI  - The stimulants.
AB  - Stimulants are the most commonly prescribed psychotropic medications in child
      psychiatry, used generally for the treatment of attention deficit hyperactivity
      disorder (ADHD). In this article, the authors summarize the literature on the
      prevalence of use, neurobiology, and pharmacology of stimulants. Likewise, recent
      studies on the use of stimulants are reviewed, such as their use in specific ADHD
      populations including those with conduct disorder, girls, preschoolers,
      adolescents, and adults. Clinical guidelines for the management of children and
      adolescents receiving stimulants are offered, and treatment strategies are
      delineated for ADHD subjects with comorbidity and medication-induced adverse
      effects.

PMID- 1347940
TI  - Neuroleptics in pediatric psychiatry.
AB  - At the present time, neuroleptics are indicated for the treatment of acute
      psychotic states as well as Tourette's syndrome in children and adults.
      Neuroleptics may have a useful role in the attenuation of problem behaviors, such
      as stereotypies, hyperactivity, self-injury, and aggressive outbursts in
      infantile autism, pervasive developmental disorder NOS, and mental retardation,
      but they do not improve the underlying condition. Neuroleptics are not the agents
      of first choice for treatment of hyperactivity or aggression in children who do
      not have major developmental handicaps. Common and troublesome side effects
      associated with neuroleptic use in children and adolescents include sedation,
      extrapyramidal symptoms, and withdrawal dyskinesias; therefore, close monitoring
      is required. Neuroleptics should be used cautiously and only as an adjunct to
      other nonpharmacologic interventions.

PMID- 1347941
TI  - Alpha 1-adrenoceptor properties of terazosin HCl and its enantiomers in the human
      prostate and canine brain.
AB  - The objective of the present study was to characterize the alpha 1-adrenoceptor
      binding properties of terazosin and its enantiomers in human prostate and canine
      brain. Human prostate adenomas were obtained from 7 males undergoing
      prostatectomy for symptomatic BPH and canine cerebral cortices were obtained from
      6 male beagles. Competitive displacement experiments were carried out on these
      tissue homogenates in the presence of a constant concentration ([180 pM]) of 125I
      Heat and varying concentrations of unlabelled terazosin and its enantiomers. The
      Ki of terazosin and its enantiomers were determined from these binding studies.
      The mean Ki of rac-terazosin, R(+)-terazosin, and S(-)-terazosin in human
      prostate was 3.6 nM, 3.8 nM, and 2.8 nM, respectively. The differences between
      these mean Ki values were not statistically significant. The mean Ki of rac
      terazosin, R(+)-terazosin, and S(-)-terazosin in canine brain were 6.7 nM, 8.4
      nM, and 5.6 nM, respectively. The differences between these mean Ki values were
      not significantly different. The mean Ki of terazosin and its enantiomers were
      consistently lower in the human prostate compared to canine brain (P less than
      0.05). The present study does not provide any evidence suggesting differential
      effects of terazosin enantiomers on the human prostate. The twofold difference
      between the Ki values in the prostate and brain suggests that different subtypes
      of the alpha 1-receptor might be present in these tissues.

PMID- 1347942
TI  - An interaction between p21ras and heat shock protein hsp60, a chaperonin.
AB  - Ras proteins play a crucial role in the development of neoplasia and in signal
      transduction in normal cells. In a search for proteins interacting with p21ras,
      we previously identified a protein of 60 kDa (p60) through use of a chemical
      cross-linker. Using information from partial amino acid sequencing of the
      purified protein, we isolated full-length cDNA clones encoding this 60-kDa
      protein. Nucleotide sequence analysis revealed that p60 is the murine heat shock
      protein hsp60, a chaperonin. Association of hsp60 with p21ras appears
      physiological, as the amount of hsp60 complexed to p21ras was similar even in
      cells over-expressing p21ras, and reversing the order of cross-linking and lysis
      of the cells, which releases large amounts of hsp60 from mitochondria, did not
      alter the amount of hsp60 cross-linked to p21ras.

PMID- 1347943
TI  - Opposing tonically active endogenous opioid systems modulate the mesolimbic
      dopaminergic pathway.
AB  - The mesolimbic dopaminergic system has been implicated in mediating the
      motivational effects of opioids and other drugs of abuse. The site of action of
      opioids within this system and the role of endogenous opioid peptides in
      modulating dopamine activity therein remain unknown. Employing the technique of
      in vivo microdialysis and the administration of highly selective opioid ligands,
      the present study demonstrates the existence of tonically active and functionally
      opposing mu and kappa opioid systems that regulate dopamine release in the
      nucleus accumbens, the major terminal area of A10 dopaminergic neurons. Thus,
      stimulation of mu-type receptors in the ventral tegmental area, the site of
      origin of A10 dopaminergic neurons, increases dopamine release whereas the
      selective blockade of this opioid receptor type results in a significant decrease
      in basal dopamine release. In contrast, stimulation of kappa-type receptors
      within the nucleus accumbens decreases dopamine release whereas their selective
      blockade markedly increases basal dopamine release. These data show that tonic
      activation of mu and kappa receptors is required for the maintenance of basal
      dopamine release in the nucleus accumbens. In view of the postulated role of the
      mesolimbic system in the mediation of drug-induced alterations in mood and
      affect, such findings may have implications for the treatment of opiate
      dependence and affective disorders.

PMID- 1347944
TI  - Cell adhesion molecules as targets for Hox genes: neural cell adhesion molecule
      promoter activity is modulated by cotransfection with Hox-2.5 and -2.4.
AB  - In an effort to determine whether homeobox genes modulate the activity of the
      promoter of the mouse neural cell adhesion molecule (N-CAM) gene, we have carried
      out a series of cotransfection experiments using NIH 3T3 cells. Plasmids were
      constructed containing Xenopus laevis Hox-2.5 and -2.4 coding sequences linked to
      a human cytomegalovirus promoter (CMV-Hox-2.5 and CMV-Hox-2.4). A 4.9-kilobase
      DNA fragment containing 5' flanking and first exon sequences of the mouse N-CAM
      gene was linked to a chloramphenicol acetyltransferase (CAT) reporter gene (N-CAM
      Pro-CAT). Cotransfection with CMV-Hox-2.5 and N-CAM-Pro-CAT resulted in a strong
      induction of CAT activity. The N-CAM promoter contained two potential homeodomain
      binding sites (sites I and II) within a 47-base-pair segment (512-559 base pairs
      upstream of the ATG codon in the first exon of the N-CAM gene). This segment was
      linked to a minimal promoter (simian virus 40 early) and a downstream CAT gene.
      Although this construct was transcriptionally active at a low level in NIH 3T3
      cells, cotransfection of CMV-Hox-2.5 resulted in CAT activity that was greatly
      elevated. Mutational studies revealed that it was the homeodomain binding site II
      sequence that was required for this regulation. In contrast, cotransfection with
      CMV-Hox-2.4 eliminated the CAT activity that was driven by the CMV-Hox-2.5
      construct. Thus, the products of two related Hox genes, which are located
      adjacent to each other in the Hox-2 complex, can differentially modulate
      transcription from the promoter of a cell adhesion molecule gene. The results
      suggest that the N-CAM gene is likely to be a target for regulation by Hox gene
      products.

PMID- 1347945
TI  - Identification of the promoter of the myelomonocytic leukocyte integrin CD11b.
AB  - The CD11b (or macrophage-1 antigen; MAC-1) subunit of the leukocyte integrin
      family forms a noncovalently associated heterodimeric structure with the CD18
      (beta) subunit on the surface of human granulocytes and monocyte/macrophages,
      where it enables these myeloid cells to participate in a variety of adherence
      related activities. Expression of the CD11b subunit is restricted to cells of the
      myelomonocytic lineage and depends upon the stage of differentiation with the
      most mature myeloid cells expressing the highest levels of CD11b. To study the
      regulation of CD11b expression, a genomic clone corresponding to the 5' region of
      the CD11b gene was isolated from a human chromosome 16 library. Primer extension
      and RNase protection assays identified two major transcriptional start sites,
      located 90 base pairs and 54 base pairs upstream from the initiation methionine.
      DNA sequence analysis of 1.7 kilobases of the 5' flanking sequence of the CD11b
      gene indicated the absence of a "CAAT" or "TATA" box; however, potential binding
      sites for the transcription activators Sp1, PU.1, ets, and AP-2 are present, as
      well as retinoic acid response elements. The 1.7-kilobase CD11b promoter sequence
      displayed functional activity in transient transfection assays in the monocytic
      cell line THP-1 and the myeloid cell line HL-60. In contrast, this 1.7-kilobase
      promoter sequence did not display functional activity in the Jurkat T-lymphoid
      cell line. Detailed characterization of the CD11b promoter sequence should
      provide insight into the molecular events regulating the tissue-specific and
      developmental stage-specific expression of the CD11b molecule in myelomonocytic
      cells.

PMID- 1347946
TI  - Extensive genetic diversity in the HLA class II region of Africans, with a
      focally predominant allele, DRB1*1304.
AB  - Molecular HLA class II typing of greater than 1700 individuals from The Gambia in
      West Africa and Malawi in South-Central Africa revealed a striking diversity of
      HLA DRB-DQB haplotypes as defined by restriction fragment length polymorphism
      (RFLP); this diversity is twice as extensive as that found in northern Europeans.
      Despite this diversity, sequence and PCR/oligonucleotide analysis showed that the
      recently described variant DRB1*1304 is the commonest DRB1 allele in The Gambia.
      The sequence, geographical distribution, and RFLP association of this allele,
      together with homozygosity test results, suggest that DRB1*1304 may have arisen
      from DRB1*1102 and have reached its remarkably high frequency as a result of
      recent directional selection. The prevalence of this unusual allele has
      implications for trials of subunit vaccines in this area. The extensive and
      distinctive HLA class II region polymorphism in sub-Saharan Africans is
      consistent with evidence from other genetic loci implying an African origin of
      modern Homo sapiens.

PMID- 1347947
TI  - Characterization of a growth factor that binds exclusively to the erbB-2 receptor
      and induces cellular responses.
AB  - The erbB-2 oncogene encodes a 185-kDa transmembrane protein that has been
      suggested to be a growth factor receptor. We have previously identified and
      purified a 30-kDa growth factor (gp30) that is a ligand for the p185erbB-2
      protein that at high concentrations induces growth inhibition of cells with erbB
      2 amplification. We now report the purification and characterization of a protein
      from SKBr-3 human breast cancer cells with a molecular mass of 75 kDa (p75) that
      is a p185erbB-2 ligand. An affinity column coupled to the extracellular domain of
      p185erbB-2 was used for the purification. We found that p75 induced tyrosine
      phosphorylation of the erbB-2 oncoprotein, as determined by in vivo and in vitro
      phosphorylation and phosphoamino acid analysis. p75, as well as gp30, stimulated
      cell proliferation and colony formation of cells overexpressing erbB-2. The
      specificity of this effect was confirmed by showing that the antiproliferative
      effects of soluble erbB-2 extracellular domain were reversed by either p75 or
      gp30. p75 did not show binding to the epidermal growth factor receptor and had no
      growth effects on cells overexpressing epidermal growth factor receptor. These
      data show that SKBR-3 cells, which exhibit erbB-2 amplification and
      overexpression, secrete a growth factor that binds and activates p185erbB-2
      specifically.

PMID- 1347948
TI  - Functional expression of human mdr1 in the yeast Saccharomyces cerevisiae.
AB  - Development of multiple drug resistance in tumor cells involves amplification of
      the mdr1 gene product, a 170-kDa plasma membrane glycoprotein that is an ATP
      driven pump that extrudes the drugs. Human mdr1 (also designated as PGY1) cDNA
      was expressed in yeast cells by using the promoter and translational initiation
      signal of a related yeast gene, STE6. Immunoblotting of subcellular fractions
      showed that all of the Mdr1 (also known as P glycoprotein) was associated with
      the particulate material. Immunofluorescence microscopy revealed that the
      majority of the Mdr1 was localized to the plasma membrane (although a significant
      amount was also found in the endoplasmic reticulum). In contrast to mammalian
      cells, Mdr1 was not glycosylated in yeast. Nevertheless, some, if not all, of the
      Mdr1 made in yeast was properly folded and functional because it could be
      photoaffinity labeled specifically with 8-azido-ATP and because cells
      overexpressing Mdr1 displayed increased resistance towards valinomycin, an
      ionophore known to interact with Mdr1 in animal cells. Hence, a human polytopic
      membrane protein was correctly inserted into the yeast plasma membrane, and
      glycosylation was not required for its function.

PMID- 1347949
TI  - ERK1 and ERK2, two microtubule-associated protein 2 kinases, mediate the
      phosphorylation of tyrosine hydroxylase at serine-31 in situ.
AB  - Tyrosine hydroxylase (TH) is phosphorylated at four sites in situ and in vivo,
      and the protein kinases that phosphorylate three of these sites
      (Ser8,Ser19,Ser40) have been identified. In intact cells, the phosphorylation of
      the fourth site (Ser31) is increased in response to phorbol esters or nerve
      growth factor (NGF). Here, we show that Ser31 is phosphorylated by ERK1 and ERK2,
      two myelin basic protein and microtubule-associated protein kinases. Extracts of
      NGF- or bradykinin-treated PC12 rat pheochromocytoma cells were fractionated on
      Mono Q columns. Protein kinase activity toward Ser31 in TH was present in two
      peaks corresponding to myelin basic protein kinase activities previously
      identified as ERK1 and ERK2. Phosphorylation of purified TH in vitro by both
      kinases was selective for Ser31 up to at least 0.6 mol of phosphate per mol of TH
      subunit. Treatment of intact PC12 cells with bradykinin or NGF increased both the
      phosphorylation of TH-Ser31 in situ and the catalytic activity of ERKs (measured
      subsequently in vitro with myelin basic protein as substrate). Pretreatment of
      the cells with genistein (a protein-tyrosine kinase inhibitor) decreased the
      bradykinin- but not the NGF-induced changes in both TH-Ser31 phosphorylation and
      ERK activity. Genistein also inhibited the increases in Ser31 phosphorylation
      produced by phorbol dibutyrate, muscarine, and Ba2+. The data indicate that ERK
      activity is responsible for phosphorylating TH at Ser31 in intact cells and
      suggest that TH-Ser31 phosphorylation may be regulated by multiple signaling
      pathways that converge at or prior to the activation of the ERKs.

PMID- 1347950
TI  - Genomic analysis using a yeast artificial chromosome library with mouse DNA
      inserts.
AB  - A yeast artificial chromosome library with mouse genomic DNA inserts has been
      constructed. The library encompasses a 2.5-fold coverage of the mouse genome,
      with an average insert size of 250 kilobases. The screening strategy uses the
      polymerase chain reaction on pooled DNAs prepared from individually stored
      clones. The usefulness of the library for chromosome walking was illustrated by
      constructing a 600-kilobase-long contig of DNA surrounding Hba-ps4, a DNA marker
      that is tightly linked to the fused (Fu) locus on chromosome 17.

PMID- 1347951
TI  - Ontogenetic differences in the psychopharmacological responses to separate and
      combined stimulation of D1 and D2 dopamine receptors during the neonatal to
      weanling age period.
AB  - The psychopharmacological responses to separate and combined stimulation of
      dopamine D1 and D2 receptors were examined in neonatal (postnatal day 3-4, P3-4),
      infant (P10-11) and weanling (P21-22) rat pups. Thirty minutes prior to testing
      rat pups received a subcutaneous (SC) injection of saline, 1.0 (P3-4, P10-11) or
      0.5 (P21-22) mg/kg of the D2 agonist quinpirole. Fifteen minutes later all
      animals received an additional SC injection of 0, 0.01, 0.1, 1.0 or 10.0 mg/kg of
      the D1 agonist SKF-38393. Pups were tested for 5 min via a time-sampling
      procedure in a humidity controlled incubator for 3- and 10-day-old animals and in
      a divided glass aquarium for 21-day-old pups. Although administration of either
      agonist alone induced increases in forward locomotion and/or sniffing behavior at
      all test ages, the adult-typical grooming response to SKF-38393 and increase in
      vertical movements in response to quinpirole were not evident until weaning.
      Similarly, although combined administration of the agonists induced synergistic
      responding at each test age, only weanlings exhibited an adult-typical
      synergistic increase in licking. Thus, although the D1 and D2 receptor subtypes
      appear to be functionally present and coupled in some fashion throughout the
      neonatal to weanling age period, ontogenetic differences are evident in the
      behavioral responses elicited by separate and combined stimulation of these
      receptor subtypes.

PMID- 1347952
TI  - Discriminative stimulus effects of cyclorphan: selective antagonism with
      naltrexone.
AB  - The opioid antagonist, naltrexone, was used to identify some of the receptor
      mechanisms responsible for the discriminative stimulus effects of cyclorphan in
      the pigeon. Subjects were trained to discriminate 10 mg/kg IM injections of
      either morphine or dextrorphan from saline injections in a two key drug
      discrimination procedure in which responding was maintained by food presentation.
      The dextrorphan-trained birds generalized to l-cyclorphan at 10 mg/kg; naltrexone
      did not alter the l-cyclorphan dose-response curve for this effect. In the
      morphine-trained group, l-cyclorphan produced only partial generalization, and
      naltrexone greatly increased the dose of l-cyclorphan necessary to produce this
      effect. These results are consistent with the conclusion that in morphine-trained
      pigeons the partial generalization to l-cyclorphan is mediated by opioid
      receptors. Moreover, limited intrinsic efficacy at mu opioid receptors may be the
      characteristic of l-cyclorphan that prevents full generalization in morphine
      trained pigeons. d-Cyclorphan produced partial generalization in both groups, but
      the involvement of opioid receptor mechanisms could not be confirmed, as 1 mg/kg
      naltrexone did not antagonize d-cyclorphan in either group.

PMID- 1347953
TI  - Effects of bupropion on core body temperature of mice.
AB  - The effects of bupropion on core body temperature of intact or reserpinized mice
      were studied. Intraperitoneal (IP) administration of bupropion to mice induced a
      dose-dependent hypothermia. The response of bupropion was decreased by the D-2
      antagonist sulpiride or pimozide, but not by the D-1 antagonist SCH 23390,
      antimuscarinic drug atropine, alpha-adrenergic blocker phenoxybenzimine, beta
      adrenergic antagonist propranolol or antiserotonergic methergoline. Reserpine
      induced hypothermia, which was reversed by bupropion administration. The reversal
      response of bupropion was reduced by propranolol, but not sulpiride, SCH 23390,
      phenoxybenzamine, atropine or methergoline. It is concluded that bupropion
      induced hypothermia may be mediated through D-2 receptor activation, while the
      reversal of reserpine-induced hypothermia by bupropion may be exerted through
      beta-adrenergic stimulation.

PMID- 1347954
TI  - Effect of 5-HT1A receptor agonists in two models of anxiety after dorsal raphe
      injection.
AB  - The purpose of the present study was two-fold. Firstly, to present a more
      comprehensive analysis of the disinhibitory effects of 5-HT1A receptor agonists
      after discrete dorsal raphe (DRN) injections (Higgins et al. 1988). Secondly, the
      effects of the 5-HT1B receptor agonist CGS12066B and the 5-HT1B/1C agonist mCPP
      were examined following injection into this nucleus. The increases in social
      interaction (SI) induced by intra-raphe injections of 8-OH DPAT (0.02-1
      micrograms), buspirone (0.04-0.2 microgram), ipsapirone (0.2 microgram) and
      gepirone (0.2-1 micrograms) under a high light unfamiliar paradigm (HLU) were
      typically due to increased bout frequency, duration and a higher incidence of
      sniff, follow, allogroom behaviour. These increases were qualitatively similar to
      those seen in control animals tested under low light/familiar (LLF) conditions,
      thus supporting the belief that the drug-induced increases in SI reflected
      decreases in anxiety. Furthermore, at doses effective under the HLU condition, 8
      OH DPAT, buspirone and gepirone failed to modify SI under conditions of minimal
      suppression (LLF paradigm). At doses which significantly increased punished
      responding in a water-lick conflict test 8-OH DPAT, ipsapirone and gepirone
      tended to also increase unpunished rates of drinking. However, in drug untreated
      rats, prior habituation to the test apparatus also increased unpunished drinking,
      suggesting some neophobia-induced suppression. At a comparatively high dose, the
      5-HT1B agonist CGS12066B (2.5 micrograms), but not the putative 5-HT1B/1C agonist
      mCPP (0.5-12.5 micrograms), increased SI under the HLU condition.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1347956
TI  - Nonionic iodinated contrast media: potential renal damage assessed with
      enzymuria.
AB  - The potential of digital subtraction angiography (DSA) to enable study of the
      physiology of renal transplantation after a single intravenous injection of
      nonionic iodinated contrast material stimulated this investigation into the
      possible nephrotoxicity of the contrast material used. Levels of urinary enzyme
      activity, used as markers of renal damage, were measured before, immediately
      after, and up to 72 hours after intravenous injection of nonionic iodinated
      contrast material in two groups of patients undergoing DSA. Twenty-six patients
      had undergone renal transplantation and 10 control patients had normal renal
      function. Both groups showed a transient rise in the level of urinary enzyme
      activity that peaked within 24 hours and returned to levels obtained before DSA
      within 72 hours. In the transplantation group, the baseline levels of enzymes
      were higher, and the response after administration of contrast material was
      greater. Nevertheless, the duration of the response was the same as in the
      control group, and the enzyme levels of all patients returned to their pre-DSA
      baseline levels.

PMID- 1347955
TI  - Subjective correlates of cigarette-smoking-induced elevations of peripheral beta
      endorphin and cortisol.
AB  - Two experiments assessed subjective and hormonal effects of smoking cigarettes
      with three different nicotine deliveries. In experiment 1, 12 males smoked two
      cigarettes on three different occasions: (1) nicotine-free; (2) their own brand
      (1.0 mg FTC-estimated nicotine delivery); or (3) 2.4 mg FTC nicotine cigarettes.
      In experiment 2, 12 males smoked cigarettes of comparable nicotine yield using a
      quantified smoke delivery system (QSDS). Blood was sampled 2 min after each
      cigarette completion. Relative to nicotine-free smoking, plasma beta-endorphin
      (BE) and serum cortisol concentrations increased after quasi-ad libitum smoking
      of 2.4 mg, but not after 1.0 mg nicotine cigarettes. Self-reported malaise
      (nausea, sickness, and unpleasantness) also increased after smoking 2.4 mg
      nicotine cigarettes; subjective distress was correlated with changes in blood BE
      and cortisol. Smoking 1.0 mg cigarettes did not increase BE or cortisol, or
      subjective distress. QSDS smoking produced hormonal and subjective effects
      similar to quasi-ad libitum smoking; however, correlations between neuromodulator
      concentrations and mood were non-significant. These findings suggest that the
      elevated levels of plasma BE and cortisol reported in some smoking studies may
      not be characteristic effects of normal smoking.

PMID- 1347957
TI  - Gz-mediated hormonal inhibition of cyclic AMP accumulation.
AB  - Hormones inhibit synthesis of adenosine 3',5'-monophosphate (cAMP) in most cells
      via receptors coupled to pertussis toxin (PTX)-sensitive guanine nucleotide
      binding (G) proteins. Mutationally activated alpha subunits of Gi2 (alpha i2)
      constitutively inhibit cAMP accumulation when transfected into cells. Cells have
      now been transfected with mutant alpha subunits of four other G proteins--Gz, a
      PTX-insensitive G protein of unknown function, and Gi1, Gi3, and G(o), which are
      PTX-sensitive. Mutant alpha z, alpha i1, and alpha i3 inhibited cAMP accumulation
      but alpha o did not. Moreover, expression of wild-type alpha z produced cells in
      which PTX did not block hormonal inhibition of cAMP accumulation. Thus, Gz can
      trigger an effector pathway in response to hormone receptors that ordinarily
      interact with PTX-sensitive Gi proteins.

PMID- 1347958
TI  - Transcription factor loading on the MMTV promoter: a bimodal mechanism for
      promoter activation.
AB  - The mouse mammary tumor virus (MMTV) promoter attains a phased array of six
      nucleosomes when introduced into rodent cells. This architecture excludes nuclear
      factor 1/CCAAT transcription factor (NF1/CTF) from the promoter before
      glucocorticoid treatment and hormone-dependent access of nucleolytic agents to
      promoter DNA. In contrast, when the promoter was transiently introduced into
      cells, NF1/CTF was bound constitutively and nucleolytic attack was hormone
      independent. Thus, induction at this promoter was a bimodal process involving
      receptor-dependent remodeling of chromatin that allows NF1/CTF loading and direct
      receptor-mediated recruitment of additional transcription factors.

PMID- 1347959
TI  - LCMV-specific, class II-restricted cytotoxic T cells in beta 2-microglobulin
      deficient mice.
AB  - Intracranial infection of normal mice with lymphocytic choriomeningitis virus
      (LCMV) causes meningitis and death mediated by CD8+ major histocompatibility
      complex (MHC) class I-restricted cytotoxic T lymphocytes (CTLs). beta 2
      Microglobulin-deficient mice (beta 2M-/-) do not express functional MHC class I
      proteins and do not produce significant numbers of CD8+ T cells. When beta 2M-/-
      mice were infected with LCMV, many died from LCMV disease and produced a specific
      response to LCMV mediated by CD4+ CTLs that were class II-restricted. In these
      mice, CD4+ CTLs may compensate for the lack of CD8+ CTLs.

PMID- 1347960
TI  - Medical therapy of peptic ulcer disease.
AB  - The gastric duodenal mucosa normally is protected from the damaging effects of
      gastric acid and pepsin by ill-defined mechanisms. Ulcers may arise when there is
      an imbalance between the aggressive and defensive factors that renders the mucosa
      susceptible to damage. A variety of factors have been identified that may favor
      the development of peptic ulcers, but no single pathophysiologic defect applies
      in all ulcer patients. In duodenal ulcers, gastric acid hypersecretion is
      observed in as many as one third of patients; however, most patients with
      duodenal ulcers secrete normal amounts of gastric acid. Decreased mucosal
      bicarbonate secretion may be important in at least some duodenal ulcer patients.
      Use of NSAIDs may cause either gastric or duodenal ulcers, probably through the
      inhibition of mucosal prostaglandin synthesis and disruption of mucosal defenses.
      Finally, a recently identified bacterium, H. pylori, causes a chronic gastritis
      that is found in the overwhelming majority of patients with duodenal ulcers and
      non-NSAID-associated gastric ulcers. This bacterium may play a pivotal role in
      ulcer pathogenesis and, especially, in ulcer recurrences. A number of drugs of
      proved efficacy are available for the treatment of acute duodenal and gastric
      ulcers. The H2 receptor antagonists administered once daily remain the mainstay
      of ulcer therapy because of their efficacy, ease of use, and excellent safety
      profile. More thorough and long-lasting acid inhibition is afforded by the
      H+/K(+)-ATPase inhibitor omeprazole. This agent also promotes more rapid ulcer
      healing, but in most patients, this minor advantage may not justify the higher
      cost. It is not known whether more rapid healing will translate into lower ulcer
      complication rates. Until further data are available, this drug may be preferable
      in patients with large or complicated ulcers. In patients with refractory ulcers,
      omeprazole is clearly superior to other available agents. Agents that promote
      mucosal defense mechanisms are becoming increasingly popular in the treatment of
      duodenal ulcers but have undergone less testing than in gastric ulcers.
      Sucralfate 1 g four times daily is equivalent to H2 antagonists in the treatment
      of duodenal ulcers and, probably, gastric ulcers. Its requirement for multiple
      daily doses makes it somewhat less attractive at present to most patients. Low-
      to medium-dose Al-containing antacids are inexpensive and efficacious in duodenal
      ulcer therapy. They should remain as therapeutic options for the compliant
      patient in whom cost considerations are important. Colloidal bismuth subcitrate
      120 mg four times a day is comparable to other agents in the acute treatment of
      duodenal ulcers and likely gastric ulcers.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1347961
TI  - Mechanisms of cyclophosphamide-induced tolerance to IE-encoded alloantigens-
      evidence of clonal deletion in MHC antigen-reactive cells for skin allograft
      rejection.
AB  - Transplantation tolerance across H-2D plus IE antigen barriers has been achieved
      when B10.Thy1.1 (Kb, IAb, IE-, Db; Thy1.1) mice were primed i.v. with 9 x 10(7)
      spleen cells plus 3 x 10(7) bone marrow cells from B10.A(5R) (Kb, IAb, IEb, Dd;
      Thy1.2) and treated i.p. with 200 mg/kg of cyclophosphamide (CP) two days later.
      The tolerant state was confirmed by prolonged acceptance of donor-type skin
      grafts, and in vitro unresponsiveness to donor antigens. From the early stage of
      tolerant state, V beta 11+ or V beta 5+ T cells expressing CD4 or CD8 accessory
      molecules were markedly decreased in the periphery of the tolerant mice.
      Moreover, neither CD4+CD8- nor CD4-CD8+ thymocytes bearing a high density of V
      beta 11 or V beta 5 were detected in the chimeric thymus. The intrathymic clonal
      deletion appeared to be maintained in some of the recipient mice even after the
      disappearance of detectable mixed chimerism in the late stage. These results
      suggest that the mechanisms of the CP-induced tolerance include the destruction
      of the IE (and probably H-2D) reactive T cells in the periphery followed by the
      intrathymic clonal deletion of T cells reactive against these antigens. These
      results directly show the strong correlation between transplantation tolerance to
      H-2 alloantigens and the disappearance of alloreactive T cells in both the
      periphery and thymus.

PMID- 1347962
TI  - Evidence that donor cells are present in the thymus of recipients undergoing a P-
      --F1 graft-versus-host reaction exacerbated by concurrent murine cytomegalovirus
      infection.

PMID- 1347964
TI  - Potentiated hypnotic action with a combination of fentanyl, a calcium channel
      blocker and an alpha 2-agonist in rats.
AB  - An investigation was made of the hypnotic-anaesthetic effects in rats of
      subcutaneous coadministration of fentanyl (25-100 micrograms.kg-1), clonidine
      (100-300 micrograms.kg-1) and verapamil (1-5 mg.kg-1). Hypnotic-anaesthetic
      efficacy was assessed via loss of the righting reflex. In the doses used, none of
      the three drugs alone was associated with appreciable hypnotic-anaesthetic
      effects. Coadministration of fentanyl and clonidine resulted in a dose-related
      enhancement of the anaesthetic potency, without change in the duration of
      hypnotic action. Verapamil coadministration failed to increase the anaesthetic
      efficacy of binary combinations of fentanyl and clonidine, but a marked
      prolongation of the duration of hypnotic action was observed (P less than 0.001).
      These results suggest the existence of unreported interactions between these
      three drugs in the production of hypnotic-anaesthetic action in rats.

PMID- 1347963
TI  - Increased production of human immunodeficiency virus (HIV) in HIV-induced
      syncytia formation: an efficient infection process.
AB  - Syncytia or multinucleated giant-cell formation is one of the major cytopathic
      effects induced by human immunodeficiency virus (HIV) infection. Cell fusion
      results from the strong interaction of CD4 molecules on the surface of the
      uninfected T cells and gp120, an external envelope glycoprotein of HIV on the
      infected T cells. We studied the production of HIV in fusion cells between MOLT-4
      and virus-infected MOLT-4/HIV cells and found that HIV production was enhanced up
      to three- to fivefold, which showed a good correlation with the appearance and
      extent of syncytia formation. Blocking the fusion by monoclonal antibody against
      a binding epitope of CD4 molecule to gp120 decreased the HIV production
      significantly. Enhancement of HIV production was observed by more than five-fold
      in comparison with chronically infected cells, which were fusion free 20 hr
      postcocultivation. Electron microscopic observation also showed the presence of
      abundant HIV particles inside the fused cells and on the outer surface. AZT
      blocked the HIV augmentation of fused cells in coculture completely. Southern
      blot analysis revealed that both integrated and unintegrated HIV DNA were highly
      accumulated in fusion cells, as compared with fusion-free MOLT-4/HIV cells. Among
      unintegrated DNA, circular and linear DNA were accumulated to a similar degree.
      Northern blot hybridization showed that rapid enhancement of all three species of
      HIV-specific RNA containing genomic (9.2 kb) and subgenomic (4.3 and 1.9 kb) RNAs
      were found 20 hr postinfection in fusion cells. These data suggest that syncytia
      formation is an extremely active infection process of HIV, by which multiple
      rounds of reinfection might take place.

PMID- 1347966
TI  - Meta-analysis of the effectiveness of prophylactic drug therapy in preventing
      supraventricular arrhythmia early after coronary artery bypass grafting.

PMID- 1347965
TI  - Comparative effects of fenoldopam mesylate and nitroprusside on left ventricular
      performance in severe systemic hypertension.
AB  - To compare the effects of fenoldopam (n = 15), a selective dopamine-1 agonist,
      and nitroprusside (n = 14) on left ventricular (LV) function in severely
      hypertensive subjects (diastolic blood pressure (BP) greater than 120 mm Hg),
      both agents were infused to reduce diastolic BP by 40 mm Hg (or less than 110 mm
      Hg). Indexes of LV systolic and diastolic functions were obtained using gated
      radionuclide angiography before the initiation of treatment and after targeted BP
      was achieved. Both fenoldopam and nitroprusside effectively reduced systolic and
      diastolic BP to target levels. Changes in heart rate, peak filling rate and
      relative end-diastolic volume were similar with both agents. Baseline ejection
      fraction increased after infusion of both drugs. The magnitude of the increase in
      ejection fraction was far greater with fenoldopam than with nitroprusside (+22%
      vs +8%; p = 0.04), despite a lesser reduction in systolic BP (-12 vs -22%, p =
      0.002). Furthermore, the reduction in relative end-systolic volume (-35 vs -20%;
      p = 0.04), and increase in the ratio of peak systolic pressure to relative end
      systolic volume (+43 vs +6%; p = 0.007) were greater after fenoldopam than after
      nitroprusside. The greater increment in parameters of LV systolic function
      produced by fenoldopam than by nitroprusside suggests an effect on LV performance
      that is independent of afterload reduction.

PMID- 1347967
TI  - Maternal uniparental isodisomy of chromosome 14: association with autosomal
      recessive rod monochromacy.
AB  - Rod monochromacy (complete congenital achromatopsia) is inherited as an autosomal
      recessive trait of unknown genetic location. The disorder is characterized by
      total absence of color discrimination because retinal cone photoreceptors do not
      develop; systemic features do not occur. A 20-year-old white female with rod
      monochromacy presented with short stature (less than 5th percentile), mild
      developmental delay, premature puberty, small hands and feet (length less than
      5th percentile), minimal dysmorphism, and a reproductive history of three
      consecutive first-trimester miscarriages. Cytogenetic analysis showed
      45,XX,rob(14;14) in all 30 cells examined. Southern analysis of DNA from the
      patient and her phenotypically normal mother and two brothers (her father is
      deceased) ascertained the parental origin of the 14;14 Robertsonian
      translocation. Analysis of RFLPs associated with nine VNTR probes and two
      dinucleotide repeat polymorphisms from chromosome 14 demonstrated that the
      patient had inherited two copies of a single allele, each of which was maternally
      derived. A fully informative RFLP analysis of three probes from chromosome 14
      enabled reconstruction of the paternal haplotype and showed the lack of any
      paternal contribution to the subject. These data are consistent with maternal
      isodisomy for all portions of chromosome 14 tested by these markers. This finding
      suggests that rod monochromacy maps to chromosome 14, and it emphasizes the
      importance of uniparental isodisomy to provide a putative chromosomal assignment
      of a gene for a rare autosomal recessive disorder.

PMID- 1347968
TI  - Common sequence motifs at the rearrangement sites of a constitutional X/autosome
      translocation and associated deletion.
AB  - Reciprocal chromosome translocations are common de novo rearrangements that occur
      randomly throughout the human genome. To learn about causative mechanisms, we
      have cloned and sequenced the breakpoints of a cytologically balanced
      constitutional reciprocal translocation, t(X;4)(p21.2;q31.22), present in a girl
      with Duchenne muscular dystrophy (DMD). Physical mapping of the derivative
      chromosomes, after their separation in somatic cell hybrids, reveals that the
      translocation disrupts the DMD gene in Xp21 within the 18-kb intron 16.
      Restriction mapping and sequencing of clones that span both translocation
      breakpoints as well as the corresponding normal regions indicate the loss of
      approximately 5 kb in the formation of the derivative X chromosome, with 4-6 bp
      deleted from chromosome 4. RFLP and Southern analyses indicate that the de novo
      translocation is a paternal origin and that the father's X chromosome contains
      the DNA that is deleted in the derivative X. Most likely, deletion and
      translation arose simultaneously from a complex rearrangement event that involves
      three chromosomal breakpoints. Short regions of sequence homology were present at
      the three sites. A 5-bp sequence, GGAAT, found exactly at the translocation
      breakpoints on both normal chromosomes X and 4, has been preserved only on the
      der(4) chromosome. It is likely that the X-derived sequence GGAATCA has been lost
      in the formation of the der(X) chromosome, as it matches an inverted GAATCA
      sequence present on the opposite strand exactly at the other end of the deleted 5
      kb fragment. These findings suggest a possible mechanism which may have
      juxtaposed the three sites and mediated sequence-specific breakage and
      recombination between nonhomologous chromosomes in male meiosis.

PMID- 1347969
TI  - Origin heterogeneity of Hb Lepore-Boston gene in Italy.
AB  - Forty-three hybrid delta-beta-globin genes were characterized by DNA sequence
      analysis and associated RFLP haplotypes in 40 families from Abruzzo and Campania,
      which are on the east and west coast of Italy, respectively. All the genes had
      the delta-globin sequence up to the exon 2 codon 87 and had the beta-globin
      sequence from IVS-2-8; between these two ends, they had 58 bp in common with the
      delta- and beta-globin genes. Thus, they were all of the Lepore-Boston type. A
      chromosomal background heterogeneity was present among the mutant genes. In fact,
      they were all associated with (+ - - - -) 5' subhaplotype, but 23/31 from
      Campania were associated with (+ +) 3' subhaplotype, whereas 12/12 genes from
      Abruzzo and 8/31 from Campania were associated with (+ -). DNA sequencing of
      homozygous subjects showed that (+ +) 3' subhaplotype was associated, at IVS-2
      74, with G, while (+ -) was associated with T; that is they were associated with
      the beta-globin gene sequence of frameworks 1 and 2, respectively. The molecular
      characteristics of this heterogeneity, as well as its geographical patterns in
      the eastern and western regions of Italy, represent strong evidence for the
      recurrent and multicentric origins of the mutation.

PMID- 1347971
TI  - Genetic variation in transforming growth factor alpha: possible association of
      BamHI polymorphism with bilateral sporadic cleft lip and palate.

PMID- 1347970
TI  - PCR amplification of alleles at the DIS80 locus: comparison of a Finnish and a
      North American Caucasian population sample, and forensic casework evaluation.
AB  - Allele and genotype frequencies for the highly polymorphic D1S80 locus were
      determined in a Finnish population sample by using PCR followed by high
      resolution PAGE and silver staining, a procedure called the amplified-fragment
      length polymorphism (Amp-FLP) technique. In 140 unrelated Finnish individuals 15
      alleles and 43 phenotypes were observed. The D1S80 locus demonstrated a
      heterozygosity of .77, and the power of discrimination was .92 in this sample
      representing a genetically isolated Finnish population. The distribution of
      observed genotypes conformed to Hardy-Weinberg expectations. In 36 mother-child
      pairs Mendelian inheritance for the alleles at the D1S80 locus could be
      demonstrated in all cases, and no mutations were observed. The usefulness of the
      D1S80 locus for forensic casework was assessed by using Amp-FLP analysis of the
      D1S80 locus in 36 forensic cases including 18 rapes, 14 homicides, and 4 other
      violent crimes. In most cases valuable information was obtained using the Amp-FLP
      technique, and in no case was there indication of either false-positive or false
      negative results.

PMID- 1347972
TI  - Identification of heterogeneous PrP gene deletions in controls by detection of
      allele-specific heteroduplexes (DASH)

PMID- 1347973
TI  - Reformulation and drop size of apraclonidine hydrochloride.
AB  - We performed a prospective, double-masked, placebo-controlled, six-period, cross
      over study in which normal subjects were randomly assigned to treatment and
      compared three different formulations of apraclonidine hydrochloride (the present
      commercially available formulation, and formulations with
      hydroxypropylmethylcellulose or lysolecithin). We also evaluated the efficacy of
      a 16-microliters and 30-microliters drop size. The magnitude and duration of
      decrease in intraocular pressure was comparable for all formulations. Most
      subjects tolerated all formulations well with only a few reporting any side
      effects. The best-tolerated formulation was 0.5% apraclonidine hydrochloride
      delivered with a 16-microliters drop size. Dry mouth developed frequently with
      the commercially available 1% apraclonidine solution. Blurred vision complicated
      the use of the formulation containing hydroxypropylmethylcellulose. Both dry
      mouth (P less than .05) and blurred vision (P = .004) were statistically
      significant side effects.

PMID- 1347974
TI  - Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission.
AB  - Part of the regulation of gastrointestinal (GI) smooth muscles is provided by
      nonadrenergic noncholinergic (NANC) nerves. Stimulation of these nerves, either
      by field stimulation or via neural reflex pathways, elicits hyperpolarization of
      postjunctional smooth muscle membranes referred to as inhibitory junction
      potentials and relaxation. The transmitter(s) that mediate NANC inhibitory neural
      transmission have been a controversial topic for nearly 30 years. Recent evidence
      suggests that nitric oxide (NO) may serve as a NANC inhibitory transmitter in the
      GI tract. This hypothesis is supported by the following. 1) Immunohistochemical
      studies have shown that the enzyme necessary for NO synthesis is expressed in
      enteric neurons. In vitro studies of muscles from nearly all levels of GI tract
      have also shown that arginine analogues, which inhibit NO synthesis, reduce
      inhibitory effects of NANC neurotransmission. Effects of arginine analogues can
      be restored by addition of excess L-arginine, the substrate for NO synthesis.
      These data suggest that NO can be synthesized by enteric nerves. 2) Bioassays
      have demonstrated nerve-evoked release of a substance that has been identified as
      NO during NANC nerve stimulation. Oxyhemoglobin, known to bind to and sequester
      NO, also blocks NANC responses. These data suggest that NO is released into
      extracellular fluid during nerve stimulation. 3) Addition of NO causes rapid
      hyperpolarization of GI smooth muscle cells and relaxes muscles strips. These
      effects are similar to NANC nerve responses. NO and electrical field stimulation
      also increase tissue guanosine 3',5'-cyclic monophosphate, which may be the
      second messenger involved in NANC responses. 4) Removal of NO is easily
      accomplished by its rapid spontaneous breakdown in physiological solutions. 5)
      The pharmacology of NO and the NANC neurotransmitter in many preparations is
      similar, e.g., oxyhemoglobin blocks responses to NANC nerve stimulation and to
      exogenous NO. In summary, it would appear that many of the criteria necessary for
      NO to be considered a neurotransmitter have been satisfied.

PMID- 1347975
TI  - Actions of somatostatins on gastric smooth muscle cells.
AB  - The effects of somatostatin-28, somatostatin-14, and a synthetic somatostatin
      octapeptide analogue, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Nal-NH2 (cyclo SS-8) were
      examined on contraction of dispersed gastric smooth muscle cells from guinea
      pigs. The somatostatins did not cause contraction of gastric smooth muscle cells,
      nor did they inhibit carbachol-stimulated contraction. However, they reversed
      vasoactive intestinal peptide (VIP)-induced inhibition (relaxation) of carbachol
      stimulated contraction. Somatostatin-28 had a half-maximal effect (EC50) at 1.6
      +/- 0.8 nM, cyclo SS-8 at 0.6 +/- 0.3 nM, but somatostatin-14 had no effect even
      when used in concentrations as high as 1 microM. Incubation of muscle cells with
      peptidase inhibitors phosphoramidon (1 microM) plus amastatin (10 microM) had no
      effect on the EC50 of somatostatin-28 or cyclo SS-8 but increased the potency of
      somatostatin-14 greater than 1,000-fold. When peptides were incubated with muscle
      cells and the products applied to high-performance liquid chromatography, cyclo
      SS-8 was not degraded, but somatostatin-14 was rapidly degraded when present
      alone, and the addition of peptidase inhibitors partially inhibited the
      degradation. Cyclo SS-8 had its maximal effect at 0.5-1 min and inhibited
      relaxation induced by VIP, isoproterenol, glucagon, or dibutyryl adenosine 3',5'
      cyclic monophosphate (DBcAMP). Cyclo SS-8 partially inhibited the increase in VIP
      stimulated cAMP. Preincubation with pertussis toxin blocked the inhibitory action
      of cyclo SS-8 on VIP or DBcAMP-induced relaxation. These results indicate that
      gastric smooth muscle cells rapidly degrade somatostatin-14 and suggest that
      muscle cell peptidases could have a major effect on the actions of somatostatin
      14.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1347976
TI  - Prostaglandins and modulation of small bowel myoelectric activity.
AB  - We explored the effects of prostaglandins (PG) F2 alpha and E2 on the motor and
      myoelectric activity of the small intestine using closed intra-arterial
      injections in conscious chronically instrumented dogs. PGF2 alpha (0.125-5
      micrograms) and PGE2 (1-10 micrograms) were injected via a T tube into a branch
      of the superior mesenteric artery perfusing a 15-cm segment of jejunum.
      Experiments were performed on four dogs in which the recording devices had been
      implanted above, below, and within the perfused segment. PGF2 alpha given during
      phase I of the migrating myoelectric complex cycle induced phasic contractions in
      the perfused segment of intestine in a dose-dependent manner. Atropine (50-100
      micrograms), hexamethonium (15 mg), or TTX (10-15 micrograms) administered before
      the injection of PGF2 alpha failed to inhibit the effects of PGF2 alpha. In
      contrast pretreatment of the perfused segment with verapamil (2.5 mg) or PGE2 (1
      5 micrograms) abolished the effects of PGF2 alpha. Moreover, PGE2 injected 5 min
      after the administration of PGF2 alpha inhibited the PGF2 alpha-induced
      contractions. Administration of PGE2 alone (3-10 micrograms) before the arrival
      of phase III activity in the perfused segment abolished phase III from this
      segment of intestine. Our studies indicate opposing effects of PGF2 alpha and
      PGE2 on small intestinal myoelectric and contractile activities. PGF2 alpha has a
      direct excitatory effect on the intestinal smooth muscle, which is calcium
      channel dependent but independent of intrinsic nerves. PGE2 has an inhibitory
      effect both on the spontaneous and PGF2 alpha-induced small intestinal
      myoelectric and contractile activity.

PMID- 1347977
TI  - Gastric mucosal hyperemia due to acid backdiffusion depends on splanchnic nerve
      activity.
AB  - Acid backdiffusion through a disrupted gastric mucosal barrier leads to an
      increase in gastric mucosal blood flow (MBF). This response involves afferent
      neurons that pass through the celiac ganglion. The present study examined the
      neural pathways that underlie the rise in MBF caused by gastric perfusion with
      15% ethanol in 0.15 N HCl. MBF was measured by the hydrogen gas clearance
      technique in urethan-anesthetized rats. Mucosal hyperemia due to acid
      backdiffusion was not changed by acute bilateral subdiaphragmatic vagotomy but
      was blocked by acute removal of the celiac-superior mesenteric ganglion complex
      or acute bilateral transection of the greater splanchnic nerves. Hexamethonium
      (85 mumol/kg iv) also attenuated the rise in MBF due to acid backdiffusion,
      whereas guanethidine (0.225 mmol/kg sc) had no effect. None of the procedures and
      drug treatments altered basal MBF to a significant extent. Transection of the
      splanchnic nerves, hexamethonium, and guanethidine lowered mean arterial blood
      pressure, but hypotension as such did not significantly influence the hyperemic
      response under study. Taken together, the previous and present data indicate that
      the rise in MBF caused by acid backdiffusion depends on the integrity of afferent
      and efferent neural pathways that run in the splanchnic nerves and through the
      celiac ganglion. The efferent pathway involves ganglionic transmission through
      nicotinic acetylcholine receptors but is independent of noradrenergic neurons.

PMID- 1347978
TI  - Nicotine stimulates esophageal peristaltic contractions in cats by a central
      mechanism.
AB  - The aim of the present study was to 1) characterize nicotine-induced peristalsis
      in the feline esophagus and 2) determine the site of action of nicotine.
      Experiments were done on ketamine-sedated cats. Esophageal contractions were
      measured using a multilumen catheter assembly system. After recording 1 degree
      and 2 degrees peristaltic sequences nicotine (50-100 micrograms/kg iv) was
      administered. Nicotine induced a peristaltic contraction through the esophageal
      striated and smooth muscle part of the esophagus, which was not associated with
      any mylohyoid electromyogram activity or pharyngeal response, although the upper
      esophageal sphincter did relax. Addition of either atropine (20-50 micrograms/kg
      iv) or hexamethonium (10-20 mg/kg iv), a peripherally acting nicotinic
      antagonist, did not affect the striated muscle portion of the nicotine-induced
      esophageal contractile response but antagonized the smooth muscle response.
      However, mecamylamine (0.5-1 mg/kg iv), a ganglionic antagonist that crosses the
      blood-brain barrier, abolished the esophageal response to nicotine.
      Succinylcholine (0.5-1 mg/kg iv) abolished the striated muscle response without
      affecting the nicotine-induced smooth muscle contractility. Finally, the nicotine
      induced peristaltic sequence was abolished after bilateral cervical vagotomy. In
      conclusion, nicotine, administered peripherally, activates central brain stem
      mechanisms that mediate a peristaltic sequence through the feline esophagus.

PMID- 1347979
TI  - Successful autograft with peripheral blood stem cells in a child with T
      lymphoblastic leukemia.
AB  - Peripheral blood stem cells (PBSC) were collected by two leukaphereses and
      cryopreserved in a 3-year-old girl with T-lymphoblastic leukemia; this was after
      remission was induced by an investigative regimen when she failed to respond to a
      first-line induction therapy. The patient received marrow-ablative chemotherapy
      4.5 months after the diagnosis; this was followed by the infusion of thawed PBSC
      (203 x 10(4) CFU-GM/kg). The peripheral granulocyte count reached 0.5 x 10(9)/L
      by day +7 and the platelet count reached 20 x 10(9)/L by day + 9. Thereafter, the
      leukocyte count increased to 38 x 10(9)/L by day +14, with a gradual decline to
      normal levels. She has remained in unmaintained, complete remission 47 months
      after the autograft, with full school activity. This case illustrates the PBSC
      autograft is useful as an alternative to bone-marrow transplantation in a
      selected patient population, and extends the application of cure-oriented therapy
      to refractory childhood leukemia.

PMID- 1347980
TI  - Ventilatory effects of dexmedetomidine, atipamezole, and isoflurane in dogs.
AB  - Dexmedetomidine (DMED) is a novel alpha 2 adrenergic agonist that has been shown
      to have potent analgesic and anesthetic sparing effects. This study was designed
      to investigate the effects of DMED, both alone and combined with isoflurane, on
      resting ventilation, the hypercapnic response, and the hypoxic response in dogs.
      When given alone, 1 microgram/kg decreased resting ventilation by 22% but at
      larger doses (10, 20, and 100 micrograms/kg) resting ventilation increased,
      doubling at 100 micrograms/kg. Doses of 10 micrograms/kg and greater caused a
      maximum depression of 60% in the slope of the hypercapnic response, but no dose
      had a significant effect on the hypoxic ventilatory response. A dose of 3
      micrograms/kg of DMED reduced isoflurane MAC from 1.3% to 0.37%, and the
      ventilatory effects of this 1 MAC combination were intermediate between the awake
      values and those of isoflurane-anesthetized (1.3%) dogs. Atipamezole is a
      specific centrally acting alpha 2 receptor antagonist and when given with DMED in
      isoflurane-anesthetized dogs prevented the ventilatory depression. However,
      atipamezole alone also ventilatory stimulating effects, which may indicate tonic
      alpha 2 adrenergic activity. The ventilatory depression caused by DMED, either
      alone or combined with isoflurane, at doses that significantly reduce anesthetic
      requirements are relatively mild.

PMID- 1347981
TI  - Fetal neuromuscular blockade with vecuronium bromide: studies during
      intravascular intrauterine transfusion in isoimmunized pregnancies.

PMID- 1347982
TI  - 1992 International Conference of the American Lung Association and the American
      Thoracic Society. May 17-20, 1992, Miami Beach, Florida. Abstracts.

PMID- 1347983
TI  - A theoretical perspective on attention and patient education.
AB  - Understanding how people learn is critical to effective patient education. This
      article addresses the central role of attentional processes in supporting
      effective mental functioning and learning. The theoretical perspective provides a
      basis for examining attentional requirements associated with illness and the
      detrimental effects of multiple mental demands on attentional capacity and
      learning. Through therapeutic approaches that conserve and restore attentional
      capacity, patient teaching and learning can be improved.

PMID- 1347984
TI  - Molecular characterization of interleukin 12.
AB  - Interleukin 12 (IL-12), formerly known as cytotoxic lymphocyte maturation factor
      and natural killer cell stimulatory factor, is a cytokine secreted by a human B
      lymphoblastoid (NC-37) cell line when induced in culture with phorbol ester and
      calcium ionophore. This factor has been purified to homogeneity and shown to
      synergize with low concentrations of interleukin 2 in causing the induction of
      lymphokine-activated killer cells. In addition, purified IL-12 stimulated the
      proliferation of human phytohemagglutinin-activated lymphoblasts by itself and
      exerted additive effects when used in combination with suboptimal amounts of
      interleukin 2. The protein is a heterodimer composed of a 40- and a 35-kDa
      subunit. Amino acid sequence analysis confirmed predicted sequences from the
      cloned cDNAs of each subunit. Chemical and enzymatic deglycosylation of the
      heterodimer demonstrated that the 40- and 35-kDa subunits contain 10 and 20%
      carbohydrate, respectively. Structural analysis of IL-12 using site-specific
      chemical modification revealed that intact disulfide bonds are essential for
      bioactivity. The 40-kDa subunit of IL-12 was identified by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and confirmed by immunoblotting as being
      present in NC-37 cell supernatant solutions in relatively large amounts
      uncomplexed to the 35-kDa subunit. Previously it had been shown that the 40-kDa
      subunit alone does not cause the proliferation of activated human T lymphocytes
      or enhance the cytolytic activity of human natural killer cells. However, results
      obtained by site-specific chemical modification suggesting that a tryptophan
      residue is at or near the active site of IL-12 may imply a direct role of the
      subunit in interacting with the IL-12 receptor. These data may support the recent
      proposal (D.P. Gearing and D. Cosman (1991) Cell 66, 9-10) that IL-12 consists of
      a complex of cytokine and soluble receptor.

PMID- 1347985
TI  - Reversible activation of soluble guanylate cyclase by oxidizing agents.
AB  - Soluble guanylate cyclase of human platelets was stimulated by thiol oxidizing
      compounds like diamide and the reactive disulfide 4, 4'-dithiodipyridine.
      Activation followed a bell-shaped curve, revealing somewhat different optimum
      concentrations for each compound, although in both cases, higher concentrations
      were inhibitory. Diamide at a concentration of 100 microM transiently activated
      the enzyme. In the presence of moderate concentrations of diamide and 4,4'
      dithiodipyridine, causing a two- to fourfold activation by themselves, the
      stimulatory activity of NO-releasing compounds like sodium nitroprusside was
      potentiated. In contrast, higher concentrations of thiol oxidizing compounds
      inhibited the NO-stimulated activation of soluble guanylate cyclase. Activation
      of guanylate cyclase was accompanied by a reduction in reduced glutathione and a
      concomitant formation of protein-bound glutathione (protein-SSG). Both compounds
      showed an activating potency as long as reduced glutathione remained, leading to
      inhibition of the enzyme just when all reduced glutathione was oxidized.
      Activation was reversible while reduced glutathione recovered and protein-SSG
      disappeared. We propose that diamide or reactive disulfides and other thiol
      oxidizing compounds inducing thiol-disulfide exchange activate soluble guanylate
      cyclase. In this respect partial oxidation is associated with enzyme activation,
      whereas massive oxidation results in loss of enzymatic activity. Physiologically,
      partial disulfide formation may amplify the signal toward NO as the endogenous
      activator of soluble guanylate cyclase.

PMID- 1347986
TI  - Correlation of c-erbB-2 protein expression with histologic grade, lymph node
      involvement and steroid receptor status in human breast tumors.
AB  - The association of c-erbB-2 gene amplification product (p185) with histologic
      tumor type in 100 patients with primary breast cancer was determined. In 49
      patients with infiltrating ductal carcinoma p185 detection was correlated with
      histologic findings (tumor grade, lymphnode status, receptor status). Strong
      positive staining for p185 protein was found in 10 patients (20%) with
      infiltrating ductal breast carcinoma and correlated with complete negative
      estrogen/progesterone receptor status and with histologic grade G3. There was
      neither an association with lymphnode involvement nor was there any to negative
      estrogen and progesterone receptor status alone. At present, we cannot say
      whether or not there is a correlation between the degree of c-erbB-2 gene
      amplification and prognosis. Follow-up studies are necessary to determine whether
      c-erbB-2 gene amplification allows definition of a specific subset of women who
      could benefit from adjuvant therapy.

PMID- 1347987
TI  - Sulphasalazine induced hepatitis in juvenile rheumatoid arthritis.
AB  - Two 19 year old patients with juvenile chronic arthritis developed liver toxicity
      during treatment with sulphasalazine. A significant increase in the levels of
      liver enzymes in serum samples was noticed in relation to the initiation of
      treatment in one patient and to the increase in dose in the second. The enzymes
      returned to normal levels 14 days after the drug had been stopped. A rechallenge
      in one of the patients caused re-exacerbation. This is the first report of liver
      toxicity induced by sulphasalazine in juvenile chronic arthritis. As spontaneous
      liver involvement in juvenile chronic arthritis is not rare, the possibility of
      drug induced hepatitis should be recognised in these patients.

PMID- 1347988
TI  - 2d International Congress on therapy in Andrology.

PMID- 1347989
TI  - Characterization of natural populations of Nitrobacter spp. using PCR/RFLP
      analysis of the ribosomal intergenic spacer.
AB  - DNA sequences from the intergenic spacer (IGS) region of the ribosomal operon
      were amplified by the polymerase chain reaction (PCR) technique using two primers
      derived from 16S and 23S rRNA conserved sequences. The PCR products, cleaved by 4
      base cutting restriction enzymes, were used to differentiate Nitrobacter strains.
      This method offered a convenient alternative to serological testing for
      characterization of Nitrobacter isolates and enabled a large number of strains to
      be genotypically characterized easily and rapidly. This method was successfully
      used to characterize natural populations of Nitrobacter from various soils and a
      lake. A diversity was demonstrated in various soils, and in a lake both in
      freshwater and in sediments. Strains closely related to both WL and LL were found
      in these ecosystems. It seems that the diversity of Nitrobacter populations was
      not associated with global environments but may be related to the presence of
      locally coexisting niches.

PMID- 1347990
TI  - [Contribution of molecular biology to the diagnosis of familial
      hypercholesterolemias in children].
AB  - The detection of children at high risk in families with a genetic form of
      hypercholesterolemia is important for acceptance of prevention under medical
      control. However, usual lipidic parameters are difficult to interpret during
      infancy. So we studied by a molecular biology approach 11 families presenting
      with syndrome of pure hypercholesterolemia where a defect of the LDL receptor
      (LDL-R) gene was suspected (Familial Hypercholesterolemia: FH IIa). Markers of
      the LDL-R gene (Restriction Fragment Length Polymorphism RFLP) were studied with
      intragenic probes. The segregation of the abnormal gene was studied in each
      family. Our results illustrate the limits of such an approach (its heaviness and
      the fact that, in 2 families, the analysis was not informative), but also its
      advantages: indeed, in 8 families, the diagnosis was established (particularly in
      one case at birth). Moreover in 2 families the LDL-R abnormality was excluded. In
      such case, as an alternative, the hypothesis of an apo B abnormality was
      envisaged. This differential diagnosis is interesting since it permits the choice
      of an adequate treatment.

PMID- 1347991
TI  - Current excitement with D2 dopamine receptor gene alleles in substance abuse.

PMID- 1347992
TI  - Blacks, schizophrenia, and neuroleptic treatment.

PMID- 1347993
TI  - Pancreaticoduodenectomy without homologous blood transfusion in an anemic
      Jehovah's Witness.
AB  - Whipple pancreaticoduodenectomy is an accepted procedure for management of
      periampullary and pancreatic carcinomas and has modern mortality rates of less
      than 10%. The procedure is associated with significant operative blood loss.
      Therefore, blood transfusion is an important supportive measure. We report the
      case of a bleeding ampullary carcinoma in a Jehovah's Witness who refused
      transfusion of all homologous blood products. Despite a preoperative hemoglobin
      level of 51 g/L, curative pancreaticoduodenectomy was successfully performed. The
      success of the procedure can be primarily attributed to careful surgical
      technique, intraoperative autotransfusion, avoidance of postoperative
      complications, minimization of perioperative phlebotomies, use of human
      recombinant erythropoietin, and, possibly, the use of the perfluorocarbon
      emulsion Fluosol DA-20%. The case illustrates several important principles for
      the surgical treatment of patients with severe anemia who refuse transfusion of
      homologous blood products.

PMID- 1347994
TI  - C-type natriuretic peptide is a potent activator of guanylate cyclase in
      endothelial cells from brain microvessels.
AB  - An exposure of endothelial cells from rat brain microvessels to C-type
      natriuretic peptide (CNP) resulted in a rapid and large increase in cGMP
      formation. The action of CNP did not require inhibitors of phosphodiesterases to
      be observed and occurred at nanomolar concentrations. Other natriuretic peptides
      (ANP and BNP) also stimulated cGMP formation in endothelial cells from brain
      microvessels but with a potency that was at least 100 times less than that of
      CNP. In contrast, endothelial cells from the aorta showed large cGMP responses to
      low concentrations of ANP and BNP but were unresponsive to CNP up to
      concentrations as large as 100 nM. It is concluded that endothelial cells from
      brain microvessels and from aorta express different receptors subtypes for
      natriuretic peptides. Endothelial cells from brain microvessels express CNP
      specific ANPB receptors; aortic endothelial cells express ANP (and BNP) specific
      ANPA receptors. CNP may play an important role in the regulation of water and
      electrolyte movements across the blood brain barrier.

PMID- 1347995
TI  - Cloning and characterization of two forms of C-type natriuretic peptide receptor
      in rat brain.
AB  - Two similar membrane bound guanylate cyclases (GC-A and GC-B) are known as
      natriuretic peptide receptors, but have not been well characterized yet. In this
      study, we have isolated two forms of GC-B cDNA clones along with GC-A cDNA clones
      from rat brain. The two forms of rat GC-B differ from each other only by 75bp
      deletion at 3'-flanking region of the putative transmembrane domain, the shorter
      form lacking the nucleotide binding site by the deletion. Expression of these
      cDNAs on mammalian cells revealed that (1) GC-B is a specific receptor for CNP
      whereas GC-A is stimulated effectively both by ANP and BNP, and (2) the two forms
      of GC-B possess practically the same high binding affinity for CNP while the
      shorter form could not induce cGMP production by the binding of CNP. These data
      indicate that in rat brain is present the non-functional receptor for CNP caused
      by the short deletion.

PMID- 1347996
TI  - Neuronal activity triggers calcium waves in hippocampal astrocyte networks.
AB  - The recent discovery that the neurotransmitter glutamate can trigger actively
      propagating Ca2+ waves in the cytoplasm of cultured astrocytes suggests the
      possibility that synaptically released glutamate may trigger similar Ca2+ waves
      in brain astrocytes in situ. To explore this possibility, we used confocal
      microscopy and the Ca2+ indicator fluo-3 to study organotypically cultured slices
      of rat hippocampus, where astrocytic and neuronal networks are intermingled in
      their normal tissue relationships. We find that astrocytic Ca2+ waves are present
      under these circumstances and that these waves can be triggered by the firing of
      glutamatergic neuronal afferents with latencies as short as 2 s. The Ca2+ waves
      closely resemble those previously observed in cultured astrocytes: they propagate
      both within and between astrocytes at velocities of 7-27 microns/s at 21 degrees
      C. The ability of tissue astrocyte networks to respond to neuronal network
      activity suggests that astrocytes may have a much more dynamic and active role in
      brain function than has been generally recognized.

PMID- 1347997
TI  - Changes in competence determine the timing of two sequential glucocorticoid
      effects on sympathoadrenal progenitors.
AB  - We have studied the control of adrenal chromaffin cell development by
      glucocorticoids (GCs), in a reconstituted in vitro system. The development of the
      chromaffin phenotype involves two sequential, GC-dependent events: the decision
      not to become a sympathetic neuron, and the decision to express the epinephrine
      synthesizing enzyme, phenylethanolamine-N-methyltransferase (PNMT). Both
      decisions appear to be mediated by the type II GC receptor. Competence to express
      PNMT develops on a schedule in vitro which parallels that seen in vivo, but only
      in progenitors that have first failed to undergo neuronal differentiation. The
      schedule of PNMT induction is thus controlled by the time of appearance of
      neither the inducing signal nor its receptor, as previously suggested, but rather
      by a cell-intrinsic timed process in chromaffin precursors. The two effects of
      GCs are pharmacologically distinct, suggesting that the GC receptor may interact
      differently with different genes in the same cell, in a manner that changes with
      development.

PMID- 1347998
TI  - Overexpression of the p185erB-2 tyrosine kinase growth factor receptor: control
      or chaos.

PMID- 1348000
TI  - A comparison of the effect of salmeterol and salbutamol in normal subjects.
AB  - 1. The effects of salmeterol hydroxynaphthoate (50 micrograms, 8.3 x 10(-8) M)
      and salbutamol (200 micrograms, 3.5 x 10(-7) M) on sGaw were compared in a double
      blind, placebo-controlled, randomised study in 10 normal subjects. 2. SGaw
      increased by 29% (14-43) (mean (CI)), 5 min after salmeterol and by 35% (19-51)
      at 15 min compared with an increase of 32% (14-51) and 37% (10-63) after
      salbutamol and 4% (-3-11) and 8% (0-16) after placebo. 3. The mean area under the
      sGaw-time curve (AUC480) after salmeterol inhalation was 22,500 kPa-1 (10,100
      39,500) compared with 14100 kPa-1 (8020-24,500) after salbutamol and 5300 kPa-1
      (1500-10,400) after placebo. 4. Salmeterol produced a significantly prolonged
      bronchodilator effect compared with salbutamol in normals.

PMID- 1347999
TI  - Inhaled beta 2-adrenoceptor agonists in asthma: help or hindrance?
AB  - Conventional low doses of inhaled beta 2-adrenoceptor agonists produce effective
      bronchodilation without systemic effects. Higher doses of inhaled beta 2
      adrenoceptor agonists may produce substantial improvements in bronchodilator
      response, which may be helpful to patients with more severe airway obstruction.
      At higher than recommended doses, in asthmatic patients, fenoterol appears to
      cause greater dose-related systemic beta 2-responses compared with salbutamol or
      terbutaline, although there is no evidence to suggest that fenoterol is any less
      beta 2-selective in vivo. Furthermore, tolerance develops to systemic but not to
      bronchodilator effects during chronic treatment with inhaled beta 2-adrenoceptor
      agonists. The link between asthma mortality and systemic adverse effects of
      inhaled beta 2-adrenoceptor agonists at present remains unproven. A critical
      reappraisal of the regular use of inhaled beta 2-adrenoceptor agonists including
      long-acting drugs is now indicated in the light of their possible adverse effects
      on disease control. Patients requiring regular use of inhaled beta 2-adrenoceptor
      agonists should be given additional anti-inflammatory therapy with inhaled
      corticosteroids.

PMID- 1348001
TI  - Vasculitis in children.
AB  - Reviewed herein are the major types of vasculitis affecting children, including
      Henoch-Schonlein purpura, necrotizing vasculitis of small vessels, Kawasaki's
      disease, and, less commonly, classic polyarteritis nodosa, Wegener's
      granulomatosis, Churg Strauss syndrome, and lymphomatoid granulomatosis. The
      clinical features, diagnosis, treatment, and suspected etiologies and pathogenic
      mechanisms for each entity are discussed.

PMID- 1348002
TI  - Why NO?

PMID- 1348003
TI  - Genomic structure, induction, and production of TNF-beta.

PMID- 1348004
TI  - [XL Anniversary of the Spanish Society of Internal Medicine 1952-1992. Madrid, 7
      8 February 1992. Abstracts].

PMID- 1348005
TI  - Yeast proteins associated with microtubules in vitro and in vivo.
AB  - Conditions were established for the self-assembly of milligram amounts of
      purified Saccharomyces cerevisiae tubulin. Microtubules assembled with pure yeast
      tubulin were not stabilized by taxol; hybrid microtubules containing
      substoichiometric amounts of bovine tubulin were stabilized. Yeast microtubule
      associated proteins (MAPs) were identified on affinity matrices made from hybrid
      and all-bovine microtubules. About 25 yeast MAPs were isolated. The amino
      terminal sequences of several of these were determined: three were known
      metabolic enzymes, two were GTP-binding proteins (including the product of the
      SAR1 gene), and three were novel proteins not found in sequence databases.
      Affinity-purified antisera were generated against synthetic peptides
      corresponding to two of the apparently novel proteins (38 and 50 kDa).
      Immunofluorescence microscopy showed that both these proteins colocalize with
      intra- and extranuclear microtubules in vivo.

PMID- 1348006
TI  - Effect of lengthening lymphocyte function-associated antigen 3 on adhesion to
      CD2.
AB  - The effect of lengthening the distance in an adhesion molecule between the
      receptor binding site and the membrane anchor was studied by inserting four Ig
      like domains into the two Ig domain lymphocyte function-associated antigen 3 (LFA
      3) molecule. The extended molecule expressed in Chinese hamster ovary (CHO) cells
      bound to CD2 on T lymphocytes 4- to 20-fold more efficiently than the wild-type
      molecule at 4 degrees C. Treatment of the CHO clones with neuraminidase to remove
      sialic acid, or with deoxymannojirimycin to reduce the bulk of N-linked
      glycosylation, showed that adhesion to both the wild-type and the chimeric LFA-3
      molecules was under the influence of cell-cell repulsive forces to a similar
      extent and that these treatments had less effect than lengthening LFA-3. At
      higher temperatures, such as 22 and 37 degrees C, the efficiency of binding to
      the wild-type LFA-3 increased to levels comparable with binding to extended LFA
      3. Our results suggest that more distal locations of the adhesive binding site
      from the cell membrane anchor increase the efficiency of cell-cell adhesion by
      enhancing the frequency of receptor encounter with ligand and that more proximal
      locations of the adhesive binding site can provide efficient cell-cell adhesion
      at physiological temperatures.

PMID- 1348007
TI  - The significance of T lymphocytes in transfusion medicine.

PMID- 1348008
TI  - The impact of clotting factor concentrates on the immune system in individuals
      with hemophilia.
AB  - All reported studies to date, whether comparative or not, have shown a tendency
      toward a slower decrease in CD4+ numbers in patients receiving very high-purity
      agents with the rapidity in fall-off being affected by level of CD4+ numbers (low
      CD4+ numbers decreasing more rapidly), age (older persons showing more rapid CD4+
      cell fall-off), and anti-HIV therapy. Clearly, these observations need to be
      extended in numbers, and the high-purity agents should also be similarly compared
      with the very high-purity therapies.

PMID- 1348009
TI  - Cutaneous responses--a window on inflammatory processes.

PMID- 1348010
TI  - The effect of a single oral dose of prednisolone or cetirizine on inflammatory
      cells infiltrating allergen-induced cutaneous late-phase reactions in atopic
      subjects.
AB  - The effect of a single dose of prednisolone (20 mg) or cetirizine (10 mg) on the
      immunohistology of the cutaneous late-phase reaction was determined in a double
      blind, placebo-controlled, cross-over study in 12 atopic allergic individuals.
      The subjects were challenged with intradermal allergen (30 BU) 2 hr after
      ingestion of the drugs or placebo. The magnitude of the cutaneous reactions were
      determined at 15 min, 6 and 24 hr, and skin biopsies performed at 24 hr.
      Cetirizine produced a 50% average inhibition of the immediate weal and flare
      response (P = 0.001) and a 27% average inhibition of the 6 hr late-phase
      induration (NS). Prednisolone reduced the immediate (27%, P = 0.03) and
      significantly inhibited the late-phase reaction (53%, P = 0.02). Prednisolone
      significantly inhibited infiltration of CD45+ (total leucocytes), neutrophil
      elastase+, EG2+ (activated eosinophils) and CD25+ (IL-2R) cells (P = 0.017,
      0.005, 0.005 and 0.032 respectively). CD3, CD4, CD8 and HLA-DR expression was
      also inhibited but this was not significant. Cetirizine also reduced the numbers
      of EG2+ cells, particularly those with high counts before treatment but the
      overall results were not significant. No other changes in the cellular infiltrate
      were demonstrated when cetirizine was compared with placebo. These findings
      indicate a single dose of prednisolone significantly reduces leucocyte
      infiltration and activation as well as the magnitude of the cutaneous late-phase
      reaction.

PMID- 1348011
TI  - Prefrontal lobotomy and hypofrontality in patients with schizophrenia: an
      integration of the findings.
AB  - A case of a schizophrenic patient who suffered a frontal lobotomy is presented as
      the impetus for a discussion of an alternative neurobiologic model of
      schizophrenia to integrate the findings of prefrontal lobotomy and
      "hypofrontality". The proposal that primary temporolimbic pathology may result in
      secondary hypofunction in the prefrontal lobes is examined in light of current
      structural neuropathologic evidence. Directions for future research suggested by
      such a model are explored.

PMID- 1348013
TI  - Reversal of Vinca alkaloid resistance by anti-P-glycoprotein monoclonal antibody
      HYB-241 in a human tumor xenograft.
AB  - A panel of monoclonal antibodies (MAbs) to P-glycoprotein was developed by
      immunization of mice with multidrug-resistant human neuroepithelioma and
      neuroblastoma cells. All the anti-P-glycoprotein MAbs reacted with the
      extracellular portion of P-glycoprotein. The MAbs were examined for their ability
      to enhance accumulation of actinomycin D, vincristine, vinblastine, and
      doxorubicin in the human mdr1 transfectant cell line, BRO/pFRmdr1.6. HYB-241, an
      IgG1 anti-P-glycoprotein MAb, was the most effective modulator, increasing
      actinomycin D levels in the transfectant line by 6-fold, vincristine by 2-fold,
      and vinblastine levels by 3-fold. None of the MAbs were capable of modifying the
      accumulation of doxorubicin. HYB-241 lowered the 50% inhibitory concentration
      values of actinomycin D by 11-fold, vincristine by 6-fold, and vinblastine by 2
      fold. No effect on the 50% inhibitory concentration values of doxorubicin or
      gramicidin were seen. 111In-labeled HYB-241 localized in human tumor xenografts
      of BRO/pFRmdr1.6 in nude mice (25% injected dose/g at 120 h). Mice with
      established drug-resistant xenografts were treated with antibody 24 h prior to
      the injection of Vinca alkaloid at concentrations known to be non-growth
      inhibitory. The addition of HYB-241 at 25 mg/kg per injection prior to drug
      resulted in a significant inhibition of growth of this drug-resistant tumor.

PMID- 1348012
TI  - Production and characterization of a murine/human chimeric anti-idiotype antibody
      that mimics ganglioside.
AB  - The VL and VH from a murine anti-idiotypic antibody that mimics ganglioside have
      been cloned, sequenced, and expressed as a chimeric mouse/human IgG1 antibody.
      The chimeric antibody retained a binding specificity indistinguishable from the
      original murine antibody. The VH was a member of Vgam 3.8 family. The sequences
      are discussed in terms of ways in which proteins may mimic ganglioside epitopes.

PMID- 1348014
TI  - Allelic losses at chromosome 17p in human renal cell carcinoma are inversely
      related to allelic losses at chromosome 3p.
AB  - Recent studies have demonstrated that allelic losses at chromosome 17p are
      associated with the genesis of a wide variety of human cancers. In order to
      assess whether the rearrangement of chromosome 17p was responsible for the
      genesis of renal cell carcinoma (RCC), we used restriction fragment length
      polymorphism analysis of chromosome 17p. We studied 48 RCCs, including 6
      metastatic RCCs, from 43 patients with 5 polymorphic probes to loci within or
      near the p53 gene. Allelic losses at chromosome 17p were detected in only 6 of
      the 36 informative cases (17%), and no definitive correlation was demonstrated
      between allelic losses at 17p and the tumor stages. The 6 RCCs with allelic
      losses at 17p were histopathologically classified as a clear cell type in one, a
      mixed cell type in one, and granular cell types in the other four cases. Allelic
      losses at 17p in the clear cell type of RCC were infrequent (6%, 1 of 18), and
      were not detected even in the metastatic tumor from a highly advanced case. This
      finding suggests that allelic losses at 17p could be random genetic
      rearrangements in the case of the clear cell type of RCC. On the other hand,
      allelic losses at 17p in the granular cell type of RCC were demonstrated with a
      significantly higher frequency (44%, 4 of 9). We previously reported that allelic
      losses at 3p were specific to the clear cell type of RCC (Ogawa et al., Cancer
      Res., 51:949-953, 1991). Examination of the association of allelic losses at 17p
      with those at 3p revealed that none of 5 informative RCCs with allelic losses at
      17p showed allelic losses at 3p. Conversely, 17 of 25 informative RCCs with
      retention of 17p alleles lost alleles at 3p. Thus, an inverse relationship was
      demonstrated with statistical significance (P less than 0.01). These data suggest
      that the types of rearrangement on chromosome 17p and/or chromosome 3p can
      differentiate between the histopathological subtypes of RCC.

PMID- 1348015
TI  - Biochemical characterization of resistance to mitoxantrone and adriamycin in Caco
      2 human colon adenocarcinoma cells: a possible role for glutathione S
      transferases.
AB  - Cytotoxicity of Adriamycin on human colon adenocarcinoma cell lines was
      investigated. Concentrations of Adriamycin producing 50% inhibition were very
      similar in HT29, Sw480, Sw620, and Sw1116 cells, whereas Caco-2 cells were
      relatively insensitive. As compared to the Sw1116 cell line, Caco-2 cells were
      also insensitive to mitoxantrone. Sensitivity to cisplatin, 5-fluorouracil, or
      ethacrynic acid was comparable in both cell lines. To find the mechanism for this
      mitoxantrone and Adriamycin resistance, several potential Adriamycin-detoxifying
      systems were characterized and quantified in both Sw1116 and Caco-2 cells. No
      dramatic differences in glutathione content and expression of both selenium
      dependent- and independent glutathione peroxidase, UDP-glucuronyltransferase, and
      cytochrome P-450 were found. However, highly significant differences in
      glutathione S-transferase activity were present, the expression of both class pi
      and class alpha glutathione S-transferases being much higher in the Caco-2 cell
      line. In addition, a slightly higher content of P-170 glycoprotein was present in
      the Caco-2 cells. These findings suggest that glutathione S-transferases, and to
      a lesser extent the P-170 glycoprotein, may be involved in mitoxantrone and
      Adriamycin resistance of Caco-2 colon carcinoma cells.

PMID- 1348017
TI  - Polymorphic sites within the MCC and APC loci reveal very frequent loss of
      heterozygosity in human small cell lung cancer.
AB  - Using single-strand conformation polymorphism we have found two polymorphic
      sites, AAC to AAT at codon 511 (exon 12) and GCT to GCG at codon 708 (exon 15),
      in the MCC gene. These sites and an RsaI polymorphic site in APC allowed us to
      study 23 human small cell lung cancer (SCLC) and 7 non-small cell lung cancer
      samples for allele loss. Of the 23 SCLC samples, 21 (91%) were informative for
      one or more of these markers, and we found allele loss in more than 80% (17 of
      21). In non-small cell lung cancer samples, 5 of 7 (71%) were informative, and
      reduction or loss of one allele was found in 2 of 5 (40%). Seven cases were
      informative for both genes, loss of heterozygosity occurred for both genes in
      five, one retained heterozygosity for both, and one SCLC had loss of
      heterozygosity for APC but not for MCC. We conclude that loss of heterozygosity
      occurs frequently for MCC and APC in lung cancer of all histological types and is
      very frequent in SCLC. This suggests the presence of tumor suppressor gene(s) in
      the MCC/APC region of 5q21 involved in human lung cancer.

PMID- 1348016
TI  - Radiolabeled antibody targeting of the HER-2/neu oncoprotein.
AB  - The HER-2/neu oncogene encodes a Mr 185,000 transmembrane phosphoglycoprotein
      which is overexpressed in 25-35% of breast and ovarian neoplasms and portends a
      poor prognosis. We have studied the feasibility of targeting this oncoprotein,
      designated p185, with radioiodinated murine monoclonal antibodies (muMABs) 4D5
      and 7C2, which recognize distinct epitopes on its extracellular domain. The rates
      of internalization and catabolism of these antibodies were analyzed by cellular
      radioimmunoassay and electron microscopy. After binding to NIH3T3 HER-2/neu
      cells, which show high surface expression of p185, the muMABs were endocytosed
      via coated pits, routed to lysosomes, and degraded. Approximately 44% of 125I-4D5
      and 39% of 125I-7C2 were catabolized by tumor cells after 24 h. The
      biodistribution of radiolabeled 4D5 and 7C2 were evaluated in beige/nude mice
      bearing s.c. NIH3T3 HER-2/neu grafts. A high specificity of localization was seen
      with tumor:organ ratios of activity generally ranging from 5:1 to 30:1. However,
      the percentage injected dose of radioactivity per gram of tumor declined sharply
      from 25% at 24 h to 5% at 120 h postinjection. Treating the animals with 400-700
      muCi 131I-4D5 caused a marked inhibition of tumor growth, although no mice were
      cured. Unlabeled 4D5 had no effect on tumor progression in this model, but
      administering 400-700 muCi of 131I-DA4-4, an isotype-matched irrelevant muMAB,
      resulted in an intermediate degree of growth retardation. Analysis of kinetic
      blood data and whole-body time-activity curves indicated that the irrelevant
      conjugate remained in the body 2-3 times longer than 131I-4D5. Radioiodinated
      anti-HER-2/neu muMABs are attractive agents for radioimmunodiagnosis and
      radioimmunotherapy of aggressive HER-2/neu-positive breast and ovarian
      carcinomas, but effective strategies for retarding intratumoral catabolism may be
      necessary to optimize their clinical utility.

PMID- 1348019
TI  - Differentiation of both rod and cone types of photoreceptors in the in vivo and
      in vitro developing pineal glands of the quail.
AB  - The avian pineal is a photo-endocrinal organ and is considered to synthesize and
      secrete melatonin in an intrapineal rhythm which can be modified by direct light
      stimulation of the pineal photoreceptors. Since the avian retina contains
      numerous different types of photoreceptors, at least 6 types in the quail retina,
      it is interesting to ask how many types of photoreceptors are present in the
      avian pineal. In the present study, we have identified two types of
      photoreceptors in the quail pineal organ, one appears rod-like and the other cone
      like, using an immunohistochemical method with highly specific anti-chicken
      rhodopsin and anti-iodopsin monoclonal antibodies. Rhodopsin-immunoreactive (Rho
      I) cells were much larger in number than iodopsin-immunoreactive (Iodo-I) cells.
      During pineal development, Rho-I cells were first observed at embryonic day 13
      (E13: 13 days of incubation), whereas Iodo-I cells were found at day E15. Rho-I
      cells showed numerous neurite-like processes, but Iodo-I cells had few, if any,
      processes. We developed a new culture system for avian pineal cell
      differentiation by seeding cells on nitrocellulose membrane filters. By this
      method both types of pineal photoreceptors differentiated in vitro: Rho-I cells
      were much larger in number and had much more fine processes than Iodo-I cells,
      similar to those seen in the intact developing pineal. With the new culture
      system the relation between pineal photoreceptor differentiation and sympathetic
      innervation was examined in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348018
TI  - Morphological changes of V-79 cells after equinatoxin II treatment.
AB  - Morphological observations on the V-79-379 A cells after treatment with
      equinatoxin II (EqT II), isolated from the sea anemone Actina equina L., and
      fetal calf serum (FCS) treated toxin were examined by transmission electron
      microscopy. Our results showed that the cells incubated with FCS treated EqT II
      were almost ultrastructurally unaltered. When the cells were treated with low
      concentrations of EqT II alone cell ultrastructure was altered with the evidence
      of numerous blebs and decreased microvilli number on the cell surface and
      appearance of numerous vesicles in the Golgi regions. High concentrations of EqT
      II caused disintegration of plasmalemma and intracellular membranes as well as
      degradation of cytosol.

PMID- 1348020
TI  - Perforated peptic ulcer--the changing scene.
AB  - There is a changing scene with perforated peptic ulcer. The older age of
      presentation, the increased association with non-steroidal anti-inflammatory
      drugs, associated increased debility, and resulting higher mortality in the
      elderly, are causing a rethink in management protocols. Whereas years ago most
      discussion was on whether urgent definitive surgery was the most effective
      therapy, nowadays there is a tendency to less invasive measures. A 'deliberative'
      approach, wherein not all patients require surgery, is detailed, and there may be
      an increasing role for laparoscopic perforation-sealing techniques in the
      remainder. Anti-secretory and anti-helicobacter drugs have an important role in
      post-operative care following lesser procedures than definitive surgery.

PMID- 1348021
TI  - IgG and IgA autoantibodies to C1q in systemic and renal diseases.
AB  - Antibodies to the collagen-like region of C1q have been described in patients
      with SLE and rheumatoid vasculitis. In this study the prevalence of both IgG and
      IgA C1qAb was assessed in serum samples of 385 patients with different systemic
      and renal diseases. The results demonstrate that the prevalence of IgG and IgA
      C1qAb is not restricted to the diseases in which they were originally described.
      C1qAb can also be demonstrated in patients with MCTD, Felty's syndrome,
      ankylosing spondylitis, polyarteritis nodosa, mixed cryoglobulinaemia,
      membranoproliferative glomerulonephritis, glomerulosclerosis, and patients with
      anti-glomerular basement membrane nephritis. The widespread occurrence of C1qAb
      of both immunoglobulin classes in systemic and renal diseases may provide insight
      into the mechanisms that lead to C1qAb formation.

PMID- 1348022
TI  - The First International Workshop on Physiotherapy in Juvenile Chronic Arthritis.

PMID- 1348023
TI  - Restriction fragment length polymorphisms at the GLUT4 and GLUT1 gene loci in
      type 2 diabetes.
AB  - Inherited abnormalities of the glucose transporters could explain many of the
      pathophysiological features of Type 2 diabetes including the strong familial
      predisposition to the disease. Previous studies have suggested a possible
      association between an allele of an Xba1 restriction fragment length polymorphism
      (RFLP) at the GLUT1 gene locus and Type 2 diabetes in Caucasian and Japanese
      subjects. In order to test this hypothesis further, population association
      studies were performed at the Xba1/GLUT1 and Kpn1/GLUT4 gene loci employing a
      group of diabetic patients with a strong family history for the disease. The
      frequencies of the two alleles at the GLUT1 locus were 0.28 and 0.72 in diabetic
      patients and 0.31 and 0.69 in control subjects. At the GLUT4 locus, the two
      alleles had frequencies of 0.24 and 0.76 in diabetic patients and 0.25 and 0.75
      in control subjects. These differences were not statistically significant. The
      present study does not support the hypothesis that genetic variation within the
      GLUT1 or GLUT4 gene loci may be responsible for familial susceptibility to Type 2
      diabetes.

PMID- 1348025
TI  - [Portal hypertension: beta-receptor blockers for the prevention of upper
      intestinal bleeding].

PMID- 1348024
TI  - Serum and tissue zinc concentrations in patients with endoscopic esophagitis.
AB  - Because zinc is an important metabolic requirement for growth and repair of
      squamous tissue, we questioned whether changes in serum and esophageal tissue
      zinc were present in patients with reflux esophagitis. To investigate this
      question, we prospectively studied 49 patients undergoing upper gastrointestinal
      endoscopy for symptoms of abdominal pain and discomfort; 19 patients were taking
      H2 antagonists at the time of the study. Blood was obtained to measure serum zinc
      concentrations prior to endoscopy and tissue zinc levels were obtained from
      esophageal biopsies from the distal, middle, and proximal esophagus in patients
      who were either endoscopically normal or who exhibited endoscopic esophagitis.
      Serum zinc concentrations were significantly lower in patients with endoscopic
      esophagitis compared to the endoscopically normal group (77 +/- 3.8 micrograms/dl
      vs 88 +/- 2.4 micrograms/dl, P less than 0.02). Distal esophageal tissue
      concentrations were significantly higher in patients with endoscopic esophagitis
      compared to the endoscopically normal group (200 +/- 30 micrograms/liter vs 135
      +/- 15 micrograms/liter, P less than 0.05); whereas there were no differences
      between values obtained in the proximal or middle esophagus. Serum and tissue
      zinc concentrations in patients with esophagitis receiving H2 antagonists were
      more similar to values obtained in patients who were endoscopically normal than
      to patients with endoscopic esophagitis without treatment. This study suggests
      that in endoscopic esophagitis: (1) greater amounts of zinc are concentrated in
      the rapidly proliferating distal esophageal epithelium, (2) the serum zinc pool
      may serve as a major zinc source, and (3) decreasing esophageal mucosal
      inflammation with H2 antagonists may decrease zinc loss via the esophageal
      epithelium.

PMID- 1348026
TI  - Peripheral tolerance to an islet cell-specific hemagglutinin transgene affects
      both CD4+ and CD8+ T cells.
AB  - To study the basis for immunological tolerance of peripheral tissue-specific
      antigens, a transgenic mouse line was established that expresses the influenza
      hemagglutinin (HA) on pancreatic islet beta cells (Ins-HA transgenic mice). When
      followed up to 14 months of age, Ins-HA transgenic mice did not develop
      spontaneous autoimmune disease. Upon immunization with HA-expressing viruses,
      high titers of HA-specific circulating antibody were detected; however, T cell
      responses by both the T helper and T cytolytic compartment were markedly reduced
      as compared with transgene-negative littermates, and no evidence could be found
      for islet infiltrates. Adoptive transfer of histocompatible lymphocytes from
      transgene-negative mice plus virus into irradiated Ins-HA hosts resulted in islet
      inflammation dominated by CD4+ T cells, indicating that the HA antigen was
      accessible to activated T cells. These results suggest that T cells can be
      rendered tolerant of antigens expressed outside the thymus.

PMID- 1348027
TI  - A lymphocyte differentiation and activation antigen, CZ-1, that distinguishes
      between CD8+ and unstimulated CD4+ T lymphocytes.
AB  - We report the generation and cellular reactivity of a novel rat IgM monoclonal
      antibody (mAb), CZ-1, made against mouse natural killer (NK) cells activated in
      vivo. mAb CZ-1 recognizes a molecule whose properties are consistent with that of
      a trypsin-sensitive, non-phosphatidyl inositol-linked sialoglycoprotein. The
      expression of the antigen recognized by mAb CZ-1 is restricted mostly to cells of
      the lymphoid lineage. The antigen is expressed on 10%-25% of bone marrow cells
      and 3%-5% of thymocytes. Analysis of thymocyte subpopulations indicates
      expression of the CZ-1 antigen on 100% of the NK1.1+, 27% of the CD4-CD8-, 1.1%
      of the CD4+CD8+, 1.1% of the CD4+CD8-, and 33% of the CD4-CD8+ cells. In the
      spleen, the CZ-1 antigen is expressed on B lymphocytes, NK cells, and virtually
      all CD8+ T lymphocytes. Most unstimulated CD4+ splenic T lymphocytes, monocytes
      and polymorphonuclear cells, with the notable exception of basophils, do not
      react with mAb CZ-1. CD4+ T cells activated in vivo by virus infection or in
      vitro by anti-CD3 and interleukin-2 express the CZ-1 antigen. These results
      indicate that mAb CZ-1 identifies a novel inducible lymphocyte
      activation/differentiation antigen that distinguishes between thymic and
      unstimulated splenic CD4+ and CD8+ T lymphocytes. This mAb will be a useful tool
      in the identification of lymphocyte subpopulations and in the study of the
      ontogeny and activation of these cells.

PMID- 1348028
TI  - Expression of the adhesion molecules ICAM-1 and ICAM-2 on tumor cell lines does
      not correlate with their susceptibility to natural killer cell-mediated
      cytolysis: evidence for additional ligands for effector cell beta integrins.
AB  - The LFA-1 molecule (CD11a/CD18), a member of the leukocyte (beta 2) integrin
      subfamily of the integrin supergene family, has been shown to subserve important
      function(s) in natural killer (NK) and lymphokine-activated killer (LAK) effector
      cells based on monoclonal antibody inhibition and other studies. Presently, two
      cellular ligands for LFA-1 have been identified, termed ICAM-1 and ICAM-2. In
      this study, we have examined the role of target cell ICAM-1 (CD54) and ICAM-2 in
      NK-mediated target lysis. Using a panel of tumor target cell lines, ICAM-1
      surface protein and transcript expression did not correlate with sensitivity to
      NK lysis. Compared to ICAM-1, ICAM-2 transcript expression was very low or
      undetectable in tumor cell targets, and also did not correlate with sensitivity
      to NK lysis. ICAM-1+ K562 cells and K562 cells which were rendered surface ICAM-1
      with an antisense oligonucleotide were equally sensitive to NK lysis. Finally,
      human ICAM-1- P815 cells were stably transfected with the human ICAM-1 gene, and
      both ICAM-1- P815 (wild type) and ICAM-1+ stable transfectants were equally
      insensitive to NK lysis. These studies provide evidence that ICAM-1 and ICAM-2
      are not important target cell ligands for NK effector cell LFA-1 and that other
      target cell ICAM may exist.

PMID- 1348029
TI  - Polymorphism of human immunoglobulin VH4 germ-line genes.
AB  - The human immunoglobulin VH4 gene family is thought to contain approximately 10
      germ-line genes and to exhibit little polymorphism. We report here an analysis of
      VH4 germ-line genes that were amplified from DNA of two unrelated individuals.
      Ten unique (non-repetitive) sequences were obtained from individual A and 11 from
      individual B. Nine of these sequences represent new germ-line genes, and 8/9
      exhibit only 89%-96% similarity to genes identified previously. Subsets of VH4
      genes displayed distinctive nucleotide motifs that account for most of the
      differences between them. This observation suggests that diversity in the VH4
      gene family arose from the acquisition of blocks of nucleotides, rather than by
      accumulation of point mutations. These nucleotide blocks could have been acquired
      by gene conversion or by homologous recombination. All of the VH4 genes have a
      potential N-linked glycosylation site at Asn 60, and some genes encode a second
      site at Asn 52. The VH4 gene family is larger and more polymorphic than
      appreciated previously. Immunoglobulin gene polymorphism may make a significant
      contribution to hereditary variations in the immune response and to the genetic
      predisposition to autoimmune diseases.

PMID- 1348030
TI  - Repertoire of V alpha and V beta regions of T cell antigen receptors on CD4+ and
      CD8+ peripheral blood T cells in a novel X-linked combined immunodeficiency
      disease.
AB  - The repertoire of V regions of alpha/beta+ T cell receptor (TcR) on CD4+ and CD8+
      T cells from the peripheral blood of six patients with a novel X-linked combined
      immunodeficiency was investigated by flow cytometry. The relative frequencies of
      V region subfamilies V alpha 2a on CD4+ T lymphocytes and V beta 5b and V beta
      12a on CD8+ T lymphocytes from the peripheral blood from the affected males were
      decreased significantly. Also, the relative frequencies of certain other V region
      subfamilies on CD4+ or CD8+ T cells from the peripheral blood of some patients
      were either considerably below or above the ranges found in normal subjects.
      Although there may be other explanations including an extrathymic event, we
      suggest that the abnormalities in the TcR repertoire of peripheral blood T cells
      are consistent with a dysregulation of the intrathymic maturation/selection of T
      cells that leads to deficiencies in T cell populations in the peripheral blood of
      males with this disease.

PMID- 1348031
TI  - The cell-mediated response to schistosomal antigens at the clonal level:
      development and characterization of a panel of egg antigen-specific murine T cell
      clones.
AB  - The cellular basis of the immune response underlying the granulomatous
      hypersensitivity in experimental murine schistosomiasis caused by Schistosoma
      mansoni was investigated by examining a panel of 16 egg antigen-specific T cell
      clones. The clones were derived from a sensitized T cell line by limiting
      dilution, and were selected on the basis of their strong responses against
      schistosomal egg antigens. By cytofluorographic analysis, it was determined that
      all clones were T helper cells and expressed the CD3+CD4+CD8- phenotype.
      Lymphokine analysis revealed that some clones secreted either interleukin (IL)-2
      or IL-4, but a surprisingly large number were double producers. Southern blot
      analysis verified the clonality of these T cells and indicated that the clones
      examined included at least five independent clones by the criterion of T cell
      receptor beta gene rearrangements. Despite their diversity, the clones responded
      strongly, and virtually exclusively, to egg antigen components with isoelectric
      points in the limited range of 4.7 to 5.2. The relevant antigenic egg molecules
      were shown to require processing by accessory cells for presentation to, and
      stimulation of, the T cell clones.

PMID- 1348032
TI  - Human U937 cell surface peptidase activities: characterization and degradative
      effect on tumor necrosis factor-alpha.
AB  - Surface peptidase activities on the human monocytic lineage cell line U937 were
      characterized. Two diisopropyl phosphofluoridate (DFP)-inhibitable serine
      peptidases were identified by differences in their hydrolytic activities on
      chromogenic peptides: one removed tripeptides from the free NH2-terminal end of
      the synthetic peptide Ala-Ala-Phe-p-nitroanilide (pNA) and was not inhibited by
      inhibitors of metallo-, cysteic-, and aspartic-proteinases, or by those of
      elastase-, trypsin- and chymotrypsin-like enzymes, suggesting the presence of a
      hitherto unidentified serine tripeptidyl endopeptidase; the other peptidase
      catalyzed the release of Gly-Pro from Gly-Pro-pNA and was inhibited by DFP,
      phenylmethyl sulfonyl fluoride and diprotin A, thus resembling dipeptidyl
      peptidase IV (DPP IV) with respect to its substrate specificity and inhibitor
      profile. A group of N-exo-aminopeptidase activities specifically inhibited by
      bestatin, was also detected when Ala-, Leu-, Arg- and Lys-pNA were used a
      substrates. The activities were surface associated and not secreted as determined
      by extracellular location of product and enzymatic recovery in highly purified
      U937 cell membranes. Peripheral monocytes and macrophages were found to virtually
      exhibit identical levels of these two classes of peptidase activities when
      compared to those detected on U937 cells. The relative contributions of these
      hydrolytic enzymes to the cleavage of bioactive and radioiodinated cytokines
      including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha and
      interferon-gamma was next examined. The results indicated that N-aminopeptidases
      do not appear to participate in the catabolism of any tested cytokine. In
      contrast, the most interesting finding was that both serine peptidases
      participate in TNF-alpha degradation. Analysis of the final proteolytic digestion
      products demonstrated the disappearance of the native 17-kDa molecule TNF-alpha,
      and the concomitant release of biologically inactive fragments of less than or
      equal to 2 kDa. Together, these observations indicate new roles for both the DPP
      IV-like enzyme and the tripeptidyl endopeptidase located at the surface of human
      monocytic cells, including the regulation of the extracellular TNF-alpha
      concentration. Thus, the identification of functional ectopeptidases provides
      insight into their potential role in both normal and malignant monocytic
      function.

PMID- 1348033
TI  - The CD27- subset of peripheral blood memory CD4+ lymphocytes contains
      functionally differentiated T lymphocytes that develop by persistent antigenic
      stimulation in vivo.
AB  - On the basis of expression of the T cell differentiation antigen CD27, human
      peripheral blood CD4+ memory cells can be divided into two subsets, a large
      CD45RA-CD27+ (82%) and a small CD45RA-CD27- (18%) population. Analysis of the
      functional properties of these memory T cell subsets showed that proliferative
      responses to the recall antigen tetanus toxoid (TT), shortly after booster
      immunization, were mainly confined to the CD27- population. Also, in atopic
      individuals, proliferative responses to allergens for which these individuals are
      sensitized, were limited to the CD45RA-CD27- population. After stimulation with
      CD3 monoclonal antibody and phorbol ester, CD27+ cells produced vast amounts of
      interleukin (IL)-2 but minimal amounts of IL-4, whereas in marked contrast, CD27-
      T cells secreted low levels of IL-2 and high levels of IL-4. The capacity of the
      vast majority of these latter cells to produce IL-4 was found to be a stable
      feature since high IL-4 secreting T cell clones were generated from the CD27-
      subset. These findings suggest that upon renewed as well as chronic antigenic
      stimulation in vivo, memory T cells acquire the CD45RA-CD27- phenotype and that,
      as a consequence, in this subset functionally differentiated CD4+ T cells are
      compartmentalized. Our results predict that analysis of the small CD27- subset of
      memory cells, that makes up approximately 10% of the peripheral blood T cell
      population, will provide information on the specificity and function of
      responding CD4+ T cells at a given point in time in healthy and diseased
      individuals.

PMID- 1348034
TI  - Cytoskeleton and molecular mechanisms in neurotransmitter release by
      neurosecretory cells.
AB  - The process of exocytosis is a fascinating interplay between secretory vesicles
      and cellular components. Secretory vesicles are true organelles which not only
      store and protect neurotransmitters from inactivation but also provide the cell
      with efficient carriers of material for export. Different types of secretory
      vesicles are described and their membrane components compared. Associations of
      several cytoplasmic proteins and cytoskeletal components with secretory vesicles
      and the importance of such associations in the mechanism of secretion are
      discussed. A description of possible sites of action for Ca2+ as well as possible
      roles for calmodulin, G-proteins and protein kinase C in secretion are also
      presented. Important aspects of the cytoskeleton of neurosecretory cells are
      discussed. The cytoskeleton undergoes dynamic changes as a result of cell
      stimulation. These changes (i.e. actin filament disassembly) which are a prelude
      to exocytosis, play a central role in secretion. Moreover, advanced
      electrophysiological techniques which allow the study of secretory vesicle-plasma
      membrane fusion in real-time resolution and at the level of the single secretory
      vesicle, have also provided a better understanding of the secretory process.

PMID- 1348035
TI  - Molecular analysis of a new cytoplasmic male sterile genotype in sunflower.
AB  - Mitochondrial DNA from 1 fertile and 6 cytoplasmic male sterile (CMS) sunflower
      genotypes was studied. The CMS genotypes had been obtained either by specific
      crosses between different Helianthus species or by mutagenesis. CMS-associated
      restriction fragment length polymorphisms (RFLPs) were found in the vicinity of
      the atpA locus, generated by various restriction enzymes. The organization of the
      mitochondrial genes 26S rRNA, 18S + 5S rRNA and coxII was investigated by
      Southern blot analysis. These genes have similar structures in fertile and all
      studied sterile sources. Using the atpA probe, 5 from the 6 investigated CMS
      genotypes showed identical hybridization patterns to the Petiolaris CMS line,
      which is used in all commercial sunflower hybrids. Only 1 cytoplasm derived from
      an open pollination of Helianthus annuus ssp. texanus, known as ANT1, contained a
      unique mitochondrial DNA fragment, which is distinguishable from the fertile and
      sterile Petiolaris genotypes and from all investigated CMS genotypes. Male
      fertility restoration and male sterility maintenance of the ANT1 line are
      different from the Petiolaris CMS system, which is a confirmation that a novel
      CMS genotype in sunflower has been identified.

PMID- 1348036
TI  - Isolation and characterization of arginine ester hydrolase from Heloderma
      horridum (beaded lizard) venom.
AB  - 1. An arginine ester hydrolase was isolated from Heloderma horridum (beaded
      lizard) venom by Sephadex G-75, DEAE-Sephacel and Q-Sepharose column
      chromatography, resulting in 5.4 mg of purified enzyme from 320.0 mg of crude
      venom. 2. The enzyme was shown to be homogeneous by both SDS and non-SDS disc
      electrophoresis on polyacrylamide gel at pH 8.3. 3. The enzyme possesses arginine
      ester hydrolase and transglutaminase-like activities, but did not exhibit
      clotting activity. 4. Molecular weight was determined to be ca 29 kDa, with an
      isoelectric point of 4.4. 5. The enzyme was stable to heat treatment (95 degrees
      C, 10 min) and to pH changes over the range 2-11. 6. The arginine ester hydrolase
      was inactivated by diisopropylfluorophosphate (DFP), beta-mercaptoethanol and N
      bromosuccinimide, suggesting that serine, disulfide bonds and tryptophan are
      involved in enzymatic activity. 7. Amino terminal sequences were determined and
      appear to be similar to porcine pancreatic kallikrein.

PMID- 1348037
TI  - Structure and characterization of a 50 bp repeat in intron 10 of the human
      thyroid peroxidase gene.
AB  - We have previously identified an EcoRI polymorphism detected by a human thyroid
      peroxidase (hTPO) cDNA probe, with alleles varying in size from 3.0 to 4.1 kb.
      For further characterization of this polymorphism, we have cloned the genomic
      region containing this polymorphism. Sequence analysis of a 3.2 kb EcoRI fragment
      containing the polymorphism revealed nine copies of a 50 bp direct repeat located
      1.9 kb downstream of exon 10. In 50 unrelated Caucasian individuals, the number
      of repeats was determined and varied from 9 to 31, with an average of 21. Since
      exon 10 has been shown to be alternatively spliced in hTPO mRNA, we have also
      tested whether the number of 50 bp repeats affects alternative splicing of exon
      10. We find no correlation between the number of repeats in intron 10 and the
      ratio of alternatively spliced hTPO-1 and hTPO-2 mRNA in six human thyroid
      glands.

PMID- 1348038
TI  - Activation of alpha-1 adrenergic receptors modulates the control of left/right
      sidedness in rat embryos.
AB  - Presomite stage rat embryos were cultured for 45-49 hr with medium containing
      various adrenergic agonists and antagonists. L-Norepinephrine but not D
      norepinephrine (several orders of magnitude less potent than the L-isomer at
      alpha-1 adrenergic receptors) resulted in a dose-dependent increase of situs
      inversus similar to that found for phenylephrine, an alpha-1 adrenergic agonist.
      Prazosin, an alpha-1 adrenergic antagonist, inhibited phenylephrine-induced situs
      inversus in a dose-dependent manner. Neither dexmedetomidine, an alpha-2
      adrenergic agonist, nor isoproterenol, a beta adrenergic agonist, caused situs
      inversus. These results provide pharmacological evidence that stimulation of
      alpha-1 but not of alpha-2 and beta adrenergic receptors modulates the control of
      left/right sidedness in rat embryos.

PMID- 1348040
TI  - Mechanisms underlying the protective effects of interleukin 1 in experimental
      nonsteroidal anti-inflammatory drug gastropathy.
AB  - Interleukin 1 (IL-1) has been shown to reduce the severity of experimental
      gastroduodenal ulceration, but the mechanism of action is unclear. The present
      study examined the possibility that the mechanism underlying the protective
      effects of IL-1 in experimental nonsteroidal anti-inflammatory drug (NSAID)
      induced gastropathy is related to effects on gastric acid secretion, on
      prostaglandin synthesis, and/or on neutrophil function. IL-1 alpha and IL-1 beta
      dose-dependently (1-10 micrograms/kg) reduced the severity of gastric damage
      induced by indomethacin, whereas tumor necrosis factor alpha (1-10 micrograms/kg)
      had no effect. These effects of IL-1 were not completely attributable to a
      reduction in the volume or acidity of gastric secretion during the 1-hour
      pretreatment period. Whereas IL-1 alpha and IL-1 beta significantly inhibited
      pentagastrin-stimulated acid secretion, the dose-response relationship and time
      course of actions suggested that effects on acid secretion did not fully account
      for the ability of these agents to reduce indomethacin-induced gastric injury.
      The maximally effective dose of IL-1 beta (10 micrograms/kg) in terms of
      reduction of indomethacin-induced gastric injury did not significantly affect
      gastric prostaglandin synthesis. Neutrophil function was assessed using two in
      vivo assays. IL-1 beta inhibited migration of neutrophils in response to
      intradermal injections of N-formyl-methionyl-leucyl-phenylalanine and leukotriene
      B4 (LTB4) and dose-dependently (0.1-10 micrograms/kg) inhibited LTB4-induced
      neutropenia. These effects could be mimicked by dexamethasone (1 mg/kg SC), which
      inhibited the neutropenic response to LTB4 and significantly (P less than 0.001)
      reduced the severity of indomethacin-induced gastric damage. Both IL-1 beta and
      dexamethasone could significantly reduce the extent of histologically detectable
      leukocyte margination within the gastric mucosal microcirculation after
      indomethacin administration. The results of this study suggest that effects of IL
      1 on gastric acid secretion or prostaglandin synthesis do not fully account for
      its ability to reduce the severity of experimental NSAID-induced gastropathy,
      whereas inhibitory effects of IL-1 on neutrophil function may contribute
      significantly to its protective actions.

PMID- 1348039
TI  - Repeating developmental expression of G-Hox 7, a novel homeobox-containing gene
      in the chicken.

PMID- 1348041
TI  - Mode of origin and sources of genotypic diversity in triploid gynogenetic fish
      clones (Poeciliopsis: Poeciliidae).
AB  - Most tributaries of the Rio Fuerte in northwestern Mexico contain one or more
      clones of allotriploid fish of the genus Poeciliopsis. We used multilocus
      allozyme genotypes and mitochondrial DNA (mtDNA) haplotypes to examine several
      potential modes of origin of these gynogenetic all-female fish. The allozyme
      studies corroborated earlier morphological work revealing the hybrid constitution
      of two triploid biotypes, Poeciliopsis 2 monacha-lucida and Poeciliopsis monacha
      2 lucida. Each biotype carries one or two whole genomes from the each of the
      sexual species P. monacha and P. lucida. Restriction site analysis of mtDNA
      revealed that P. monacha was the maternal ancestor of five electrophoretically
      distinguishable triploid clones. Four of five clones were marked by closely
      related, composite, allozyme/mtDNA genotypes, suggesting they had common origins
      from an allodiploid clone of the P. monacha-lucida biotype. Genotypic analysis
      revealed that all five clones arose via the "genome addition" pathway.
      Fertilization of unreduced ova in P. monacha-lucida females by sperm from P.
      monacha and P. lucida males, respectively, gave rise to both biotypes.

PMID- 1348043
TI  - Quantitative correlation between the residual activity of beta-hexosaminidase A
      and arylsulfatase A and the severity of the resulting lysosomal storage disease.
AB  - A previously suggested model for the correlation between residual activity of a
      lysosomal enzyme and the turnover rate of its substrate(s) has been extended to a
      discussion of substrate accumulation rates in individual cells and whole organs.
      With these considerations, much of the observed variability in age of onset and
      clinical phenotype, as well as the phenomenon of pseudo-deficiency, can be
      understood as the consequences of small differences in the residual activity of
      the affected enzyme. In order to experimentally verify the basic assumptions on
      which this model rests, studies were performed in cell culture. The radiolabeled
      substrates ganglioside GM2 and sulfatide were added to cultures of skin
      fibroblasts with different activities of beta-hexosaminidase A or arylsulfatase
      A, respectively, and their uptake and turnover measured. In both series of
      experiments, the correlation between residual enzyme activity and the turnover
      rate of the substrate was essentially as predicted: degradation increased steeply
      with residual activity, to reach the control level at a residual activity of
      approximately 10-15% of normal. All cells with an activity above this critical
      threshold had a normal turnover. Comparison of the results of these feeding
      studies with the clinical status of the donor of each cell line basically
      confirmed our notions but also revealed the limitations of the cell culture
      approach.

PMID- 1348042
TI  - Evolution of the mouse H-2K region: a hot spot of mutation associated with genes
      transcribed in embryos and/or germ cells.
AB  - Active gene transcription is known to promote genetic change in neighboring DNA.
      We reasoned that the change would be readily heritable if transcription was
      occurring in germ cells or early embryonic cells before the germ cells are set
      aside. The H-2K region of the major histocompatibility complex (MHC) provides a
      good vehicle for testing this hypothesis because it is replete with such genes.
      We have compared the amount of polymorphism in 240 kb of DNA contiguous with H-2K
      and 150 kb of DNA flanking a homologous duplicated region in t-haplotypes and
      inbred strains. Using 90 probes and three restriction enzymes, we find a
      staggering difference in the amount of polymorphism in the H-2K region vs. the
      duplicated region (26% vs. 0%) of t-haplotypes. The disparity in the rate of
      divergence between the two regions indicates that the spatial distribution of
      genes and their expression pattern might be important factors in sequence
      evolution. Since t-haplotypes normally show extremely limited variability among
      themselves due to their recent divergence from a single ancestor, these results
      imply that the mutation rate in the H-2K region is unusually high. This is in
      apparent contradiction to the current view that the MHC loci have evolved at the
      same rate as other loci. The implications for the evolution of the H-2K gene are
      discussed.

PMID- 1348044
TI  - Molecular genetic evidence for a founder effect in familial hypercholesterolemia
      among French Canadians.
AB  - Familial hypercholesterolemia (FH), at a prevalence of about 1 in 200 in the
      French-Canadian population, is caused by a 10-kb deletion in the low-density
      lipoprotein (LDL) receptor gene in 60% of French-Canadian FH heterozygotes. We
      genotyped 159 FH patients who carry this common mutation and 221 healthy French
      Canadian controls for five DNA restriction fragment length polymorphisms (RFLPs)
      of the LDL receptor gene. The allele numbers for four of the five RFLPs differed
      significantly (P less than 0.001) between FH patients and control subjects. Our
      results suggest that the 10-kb deletion carrier allele is associated with a
      single haplotype (called the B haplotype). In a family study including a patient
      homozygous for the 10-kb deletion, we showed that the B haplotype cosegregates
      with the deletion in affected members and that the B haplotype is also associated
      with the normal allele in some members of the family. We identified 15 different
      haplotypes for the normal allele in 10-kb deletion carrier FH heterozygotes.
      These results offer strong support, at a molecular level, for the hypothesis of a
      founder effect for the 10-kb deletion in the French-Canadian population.

PMID- 1348046
TI  - Protein C deficiency and thromboembolism: recurrent mutation at Arg 306 in the
      protein C gene.
AB  - A CGA----TGA transition in the protein C gene, resulting in an Arg306----Term
      substitution, was detected in a Swedish kindred with thrombotic disease whose
      members exhibit plasma protein C activity/antigen levels consistent with type I
      protein C deficiency. Although an identical lesion has been reported previously
      in several Dutch families, RFLP typing indicated that the Dutch and Swedish
      mutations were unlikely to be identical by descent and probably arose by
      recurrent mutation.

PMID- 1348045
TI  - Polymorphisms at the GLUT1 (HepG2) and GLUT4 (muscle/adipocyte) glucose
      transporter genes and non-insulin-dependent diabetes mellitus (NIDDM).
AB  - In order to determine the possible contribution of the GLUT1 (HepG2) glucose
      transporter gene to the inheritance of non-insulin-dependent diabetes mellitus
      (NIDDM), two restriction fragment length polymorphisms (RFLPs) and the related
      haplotypes at this locus were studied in 48 Italian diabetic patients and 58
      normal subjects. Genotype frequencies for the XbaI polymorphism were
      significantly different between patients and controls (XbaI: chi 2 = 9.80, df =
      2, P less than 0.0079). A significant difference was also found in the allele
      frequencies between NIDDM patients and controls (chi 2 = 9.39, df = 1, P less
      than 0.0022), whereas no differences were found for the StuI RFLP. No linkage
      disequilibrium was detected between the XbaI and StuI RFLPs in this sample. The
      analysis of the four haplotype frequencies (X1S1, X1S2, X2S1, X2S2) revealed a
      significant difference between diabetic patients and controls (chi 2 = 14.26, df
      = 3, P less than 0.002). By comparing single haplotype frequencies, a significant
      difference between the two groups was found for the X1S1 and X2S2 haplotypes. A
      two-allele RFLP at the GLUT4 (muscle/adipocyte) glucose transporter gene,
      detected with the restriction enzyme KpnI, was also examined; no differences were
      found between patients and controls for this RFLP. The finding of an association
      between polymorphic markers at the GLUT1 transporter and NIDDM suggests that this
      locus may contribute to the inherited susceptibility to the disease in this
      Italian population.

PMID- 1348047
TI  - Characterization of two novel polymorphisms at the human parathyroid hormone gene
      locus.
AB  - Two new polymorphisms within the human parathyroid hormone (PTH) gene are
      described. One corresponds to a C----A transversion that destroys DraII and NlaIV
      restriction sites. The other is revealed by the enzyme XmnI, and its position has
      been mapped with respect to the PTH gene. We have also identified a sequence
      change that results in the TaqI restriction fragment length polymorphism (RFLP)
      described previously at this locus and have found that this sequence change also
      results in disruption of a BstBI site. Finally, we describe a polymerase chain
      reaction (PCR)-based method that permits a rapid evaluation of the DraII and
      BstBI (TaqI) polymorphisms. The introduction of these two additional RFLPs and
      this PCR-based assay should considerably extend the power of genetic analyses of
      the human PTH gene.

PMID- 1348048
TI  - Lung involvement, the delta F508 mutation and DNA haplotype analysis in cystic
      fibrosis.
AB  - Molecular studies of cystic fibrosis (CF) have allowed the genetic analysis of
      patients by means of DNA markers and the direct analysis of the CF gene. Some
      limited observations are available on the correlation between phenotype and
      genotype. Here, we report a study on the correlation of DNA haplotypes identified
      by KM-19 and XV-2c, the presence of the delta F508 mutation and lung involvement
      in 82 unrelated CF patients. Pulmonary involvement was defined by Chrispin's
      chest X-ray score, pulmonary function, sputum microbiology, serum immunoglobulin
      (SIg) levels and Shwachman's clinical score. Patients homozygous for haplotype B
      showed worse X-ray and clinical scores, more frequent sputum colonization by
      Pseudomonas aeruginosa and Staphylococcus aureus, lower spirometric values and
      raised concentrations of SIg G, A and M, compared with patients with other
      haplotypes. When lung involvement parameters were examined in patients
      homozygous, heterozygous or null for the delta F508 mutation, no difference was
      found among the three groups. Our data indicate a significant occurrence of
      severe pulmonary involvement in patients homozygous for the B haplotype; this is
      not influenced by the delta F508 mutation. We suggest that simple DNA haplotypes
      may provide data of both diagnostic and prognostic value, without the need for
      extensive and expensive molecular analyses.

PMID- 1348049
TI  - Mapping of the Menkes locus to Xq13.3 distal to the X-inactivation center by an
      intrachromosomal insertion of the segment Xq13.3-q21.2.
AB  - During a systematic chromosomal survey of 167 unrelated boys with the X-linked
      recessive Menkes disease (MIM 309400), a unique rearrangement of the X chromosome
      was detected, involving an insertion of the long arm segment Xq13.3-q21.2 into
      the short arm at band Xp11.4, giving the karyotype 46,XY,ins(X)
      (p11.4q13.3q21.2). The same rearranged X chromosome was present de novo in the
      subject's phenotypically normal mother, where it was preferentially inactivated.
      The restriction fragment length polymorphism and methylation patterns at DXS255
      indicated that the rearrangement originated from the maternal grandfather.
      Together with a previously described X;autosomal translocation in a female Menkes
      patient, the present finding supports the localization of the Menkes locus (MNK)
      to Xq13, with a suggested fine mapping to sub-band Xq13.3. This localization is
      compatible with linkage data in both man and mouse. The chromosomal bend
      associated with the X-inactivation center (XIC) was present on the proximal long
      arm of the rearranged X chromosome, in line with a location of XIC proximal to
      MNK. Combined data suggest the following order: Xcen-XIST(XIC), DXS128-DXS171,
      DXS56-MNK-PGK1-Xqter.

PMID- 1348050
TI  - Two intragenic polymorphisms of the APC-gene detected by PCR and enzymatic
      digestion.
AB  - The gene causing adenomatous polyposis coli (APC) has recently been cloned. Three
      intragenic polymorphisms were reported to be detectable by single-strand
      conformation polymorphism analysis. Here, we describe an assay using polymerase
      chain-reaction-based amplification and subsequent enzymatic digestion of genomic
      sequences to identify polymorphic sites at nucleotide positions 1458 and 5037 of
      the APC gene.

PMID- 1348051
TI  - PCR assay for a polymorphic DdeI site in the promoter region of the human
      cystatin C gene.
AB  - A new DNA variant in the promoter region of the human cystatin C gene has been
      detected by direct sequencing. The base substitution generates a new DdeI
      restriction site, thus allowing the design of a rapid polymerase chain reaction
      assay for analysis of this polymorphism in the population.

PMID- 1348053
TI  - Binding parameters of phenytoin during monotherapy and polytherapy.
AB  - The present in vivo study elucidated the effect of other commonly comedicated
      drugs on the phenytoin (PHT) Scatchard binding parameters. Specimens of 150
      epileptic patients chronically treated with anticonvulsant drugs were analyzed.
      The results of covariance analysis suggest that phenobarbitone, ethosuximide,
      diazepam and folic acid do not alter binding of PHT to serum albumin. The
      contribution of carbamazepine and medazepam to the free fraction of PHT (decrease
      of about 0.4%) and/or Scatchard binding capacity (increase of about 1/3) is
      ambiguous and not statistically significant at the p less than 0.05 level. On the
      contrary, we found a statistically significant decrease of PHT binding in
      patients comedicated with valproic acid (VPA) and primidone (PRM). The decrease
      of about 25% in binding capacity evoked an increase of about 1% (VPA), and 1.5%
      (PRM), respectively in PHT free fraction.

PMID- 1348052
TI  - Differential response of human thymus cells to CD2 antibodies: fragmentation of
      DNA of CD45RO+ and proliferation of CD45RO- subsets.
AB  - Human thymocytes bearing the CD45RO 'memory' cell phenotype do not proliferate in
      concanavalin A (Con A)-stimulated cultures and may be destined for intrathymic
      death. To determine whether this subset would exhibit characteristics of
      programmed cell death (apoptosis), we examined the integrity of the nuclear DNA
      by gel electrophoresis. DNA fragmentation was restricted to the CD45RO+ subset of
      human thymocytes following exposure to stimulating concentrations of anti-CD2
      antibodies. Both CD45RO- and CD45RO+ subsets mobilized cytoplasmic Ca2+ following
      cell-surface CD2 ligation, but entry into the cell cycle and vigorous thymidine
      uptake were restricted to the CD45RO- subset. Our results provide a mechanism
      which may account for the failure of thymic CD45RO+ cells to respond to stimuli
      which elicit proliferation by the reciprocal CD45RA+ subset.

PMID- 1348055
TI  - Senile cataract-related accumulation of Lewis(x) glycolipid in human lens.
AB  - A glycosphingolipid that reacted positively to anti-stage-specific embryonic
      antigen-1 (SSEA-1) antiserum accumulated in human lens in association with aging
      and senile cataract formation. Since this antiserum recognizes Lewis(x) (Le(x))
      structure, Gal beta 1-4(Fuc alpha 1-3)GlcNAc-, which is a typical tumor
      associated and differentiation-related saccharide chain, the lens glycolipid was
      predicted to be a Lex antigen. The glycolipid purified from cataractous lens
      tissues was indeed a Lex glycolipid, Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1
      3Gal beta 1- 4Glc beta 1-1 ceramide. Enhanced expression of the Lex glycolipid
      may affect the organization of lens plasma membranes through Le(x)-Le(x)
      interactions, as suggested for compaction in mouse preimplantation embryos and
      embryonic teratocarcinomas, resulting in lens opacification, namely cataract.

PMID- 1348054
TI  - Growth conditions mediate differential transcription of fim genes involved in
      phase variation of type 1 pili.
AB  - Type 1 pili in Escherichia coli undergo phase variation in which individual cells
      in a population reversibly switch between piliated (Pil+) and nonpiliated (Pil-)
      states. The switching process is mediated by an invertible DNA fragment which
      contains the promoter for fimA, the gene encoding the major structural subunit of
      type 1 pili. Although type 1 pili randomly phase vary in broth cultures, many
      clinical isolates of E. coli do not express type 1 pili when cultured on agar
      media. We investigated the role of the invertible element and the upstream genes,
      fimB and fimE, in the agar-mediated suppression of pili in an agar-negative
      clinical isolate, strain 149. Southern hybridization and polymerase chain
      reaction analyses of the fimA promoter region in broth-grown 149 cells indicated
      that the invertible element was present in orientations corresponding to both
      Pil+ and Pil- phenotypes. In contrast, only one orientation of the invertible
      element, corresponding to the Pil- phenotype, was observed in strain 149 cells
      cultured on agar. A second clinical isolate, strain 2-7, which expresses type 1
      pili on agar was also examined; the invertible element was found in both the Pil+
      and Pil- orientations during growth of this strain on agar as well as in broth.
      The introduction of the fim gene cluster from strain J96 on a multicopy plasmid
      into agar-negative strain 149 resulted in the production of both J96 and 149 pili
      during growth on agar. Experiments with subclones of the J96 genes indicated that
      the presence of an intact fimB gene allowed strain 149 pili to be produced on
      agar. Differences in pilus production between agar and broth cultures appear to
      be the result of differential transcription of fimB and fimE under the two growth
      conditions. In contrast, the pattern of expression of these genes in agar phase
      variable strain 2-7 did not differ between broth- and agar-grown cells.

PMID- 1348056
TI  - Positive cooperativity in the functioning of molecular chaperone GroEL.
AB  - In the presence of its partner, GroES, the tetradecameric molecular chaperone
      GroEL binds 14 ATP molecules, half of which are hydrolyzed in a cooperative
      manner. Moreover GroEL can bind, with a positive cooperativity, more than two
      molecules of nonfolded protein rhodanese. The role of the cooperative mechanism
      in the functioning of GroEL is discussed.

PMID- 1348057
TI  - Nuclear respiratory factor 1 activation sites in genes encoding the gamma-subunit
      of ATP synthase, eukaryotic initiation factor 2 alpha, and tyrosine
      aminotransferase. Specific interaction of purified NRF-1 with multiple target
      genes.
AB  - Transcription factor nuclear respiratory factor 1 (NRF-1) was originally
      identified as an activator of the cytochrome c gene and subsequently found to
      stimulate transcription through specific sites in other nuclear genes whose
      products function in the mitochondria. These include subunits of the cytochrome
      oxidase and reductase complexes and a component of the mitochondrial DNA
      replication machinery. Here we establish that a functional recognition site for
      NRF-1 is present in the ATP synthase gamma-subunit gene extending the proposed
      respiratory role of NRF-1 to complex V. In addition, biologically active NRF-1
      sites are found in genes encoding the eukaryotic translation initiation factor 2
      alpha-subunit and tyrosine aminotransferase, both of which participate in the
      rate-limiting step of their respective pathways of protein biosynthesis and
      tyrosine catabolism. The recognition sites from each of these genes form
      identical complexes with NRF-1 as established by competition binding assays,
      methylation interference footprinting, and UV-induced DNA cross-linking. Cloned
      oligomers of each NRF-1 binding site also stimulate the activity of a truncated
      cytochrome c promoter in transfected cells. The NRF-1 binding activities for the
      various target sites copurified approximately 33,000-fold and resided in a single
      protein of 68 kDa. These observations further support a role for NRF-1 in the
      expression of nuclear respiratory genes and suggest it may help coordinate
      respiratory metabolism with other biosynthetic and degradative pathways.

PMID- 1348058
TI  - Retention of a type II surface membrane protein in the endoplasmic reticulum by
      the Lys-Asp-Glu-Leu sequence.
AB  - Soluble luminal proteins of the endoplasmic reticulum (ER) are known to be
      retained by a tetrapeptide retention signal, KDEL. We report in this
      communication that the KDEL sequence when appended to the carboxy terminus of a
      cell surface membrane protein, dipeptidyl peptidase IV (DPPIV), resulted in its
      retention in the endoplasmic reticulum of transfected Madin-Darby canine kidney
      cells as assessed by indirect immunofluorescence. Selective surface biotinylation
      revealed that about 90-95% of the expressed DPPIV was retained in the ER.
      Appendance of the sequence KDEV did not, however, result in ER retention,
      illustrating the functional specificity of the retention signal. The ER retention
      was not due to misfolding of the mutant protein, as the mutant proteins remained
      enzymatically active. Our data suggest that the KDEL receptor is able to
      recognize and recycle type II membrane proteins containing a carboxyl-terminal
      KDEL sequence and postulates the existence of such yet to be identified
      endogenous proteins.

PMID- 1348059
TI  - The structural organization of the hamster multifunctional protein CAD.
      Controlled proteolysis, domains, and linkers.
AB  - CAD is a multidomain protein that catalyzes the first three steps in mammalian de
      novo pyrimidine biosynthesis. The 243-kDa polypeptide consists of four functional
      domains; glutamine amidotransferase (GLNase), carbamyl phosphate synthetase
      (CPSase), aspartate transcarbamylase (ATCase), and dihydroorotase (DHOase).
      Controlled proteolysis of hamster CAD was found to cleave the molecule into 18
      fragments which successively accumulate and disappear during the course of
      digestion. Each fragment was isolated and partially sequenced to determine its
      location in the polypeptide chain. Proteolysis was found to usually occur at the
      junctions between the domains and sub-domains identified by sequence homology.
      All proteases of low to moderate specificity cleaved the molecule in a similar
      fashion. The rate of proteolysis widely varied and the interdomain regions were
      not always accessible to proteases. Each of the major functional domains is
      postulated to consist of subdomains. The duplicated halves of the CPSase domain
      (116 kDa) have a homologous structure consisting of 11-, 25-26-, and 21-22-kDa
      subdomains. Prolonged digestion cleaved the DHOase domain (36.6 kDa) into two
      stable species suggesting that this region is comprised of 11.5- and 15.0-kDa
      subdomains. Similarly, proteolysis of the 21-kDa catalytic subdomain of the
      GLNase domain (40 kDa) indicated a bilobal structure consisting of 12.3- and 8.5
      kDa chain segments. The connecting region between the two ATCase subdomains (16.4
      and 18 kDa) was not cleaved. Copurification of many of the domains showed that
      they remain associated by noncovalent interactions even after the connecting
      segments have been cleaved. The chain segments, the linkers, which connect the
      domains and subdomains were conserved in length but not in sequence, were
      predicted to be relatively hydrophilic and flexible but did not show a tendency
      to assume a particular secondary structure. These studies provide a more detailed
      map of the structural organization of the CAD polypeptide.

PMID- 1348060
TI  - Use of the polymerase chain reaction for the sensitive detection of St. Louis
      encephalitis viral RNA.
AB  - Polymerase chain reaction (PCR) assays were developed for the detection of RNA
      from the St. Louis encephalitis (SLE) virus. Using computer-assisted analysis of
      the MSI-7 strain SLE virus genome, two primer pairs were selected from the capsid
      coding and the membrane associated protein-coding genes, and one from the
      envelope-coding gene. Reverse transcription was primed with either specific
      oligomers or with random hexamers; these methods were compared for cDNA synthesis
      and subsequent PCR amplification with the oligomeric pairs. Random hexamers
      provided more sensitive detection of viral RNA. Each primer pair specifically
      amplified the expected sized fragment from the Parton SLE strain grown in Aedes
      albopictus cells, but did not amplify Aedes albopictus cell RNA controls. The
      technique also detected SLE virus RNA in 1 pg of total cellular RNA added to a
      background of 1 microgram boiled brain tissue, and in 0.5 pg of total RNA added
      to homogenized mosquito abdomen. PCR-based assays may be adaptable to detect SLE
      virus RNA in naturally infected mosquitoes, birds, and human cerebrospinal fluid
      and brain.

PMID- 1348061
TI  - Is diltiazem effective in treating the symptoms of (tardive) dyskinesia in
      chronic psychiatric inpatients? A negative, double-blind, placebo-controlled
      trial.
AB  - Calcium channel blockers, antiarrhythmic drugs, such as verapamil and diltiazem,
      may decrease the symptoms of tardive dyskinesia. The efficacy and safety of
      administering 60 mg diltiazem hydrochloride, four times daily for a period of 3
      weeks, was studied in a random, double-blind, crossover trial in which the drug
      was compared with placebo in 17 neuroleptic-treated, chronic psychiatric
      inpatients of both genders with (tardive) dyskinesia. The severity of the
      dyskinesia was assessed using the Abnormal Involuntary Movement Scale. Neither
      diltiazem nor placebo produced a significant decrease in the severity of the
      dyskinesia. Diltiazem did not influence the psychiatric state of the patients,
      nor did it have a significant effect on either the blood pressure or
      electrocardiographic parameters. No significant adverse drug reactions were
      elicited.

PMID- 1348062
TI  - Haase hermeneutics, or, the exegesis of the neuroleptic threshold.

PMID- 1348063
TI  - Neuroleptic treatment in alcohol hallucinosis--no evidence for increased seizure
      risk.

PMID- 1348064
TI  - The rt-PA versus streptokinase. Controversy--I.

PMID- 1348065
TI  - Effects of benzoylecgonine on the behavior of suckling rats: a preliminary
      report.
AB  - A major metabolite of cocaine, benzoylecgonine, causes behavioral activation that
      progresses to seizures when given intraventricularly to 2-week-old rats. The
      seizures are characterized by running, hopping, and vocalizing and are mixed with
      shorter-duration tonic episodes. Pretreatment with haloperidol, at a dose aimed
      at blocking stereotyped behavior, did not suppress these behaviors. In contrast,
      seizures were prevented by antiepileptic drugs, with the order of potency being
      diazepam greater than phenobarbital greater than phenytoin. We hypothesize that
      the long-lasting cocaine metabolite, benzoylecgonine, contributes to the infant
      cocaine intoxication syndrome.

PMID- 1348066
TI  - Distribution of a novel peptide in the anterior pituitary, gastric pyloric gland,
      and pancreatic islets of rat.
AB  - We used Western blot and immunohistochemical methods to investigate the
      biochemical characteristics and cellular distribution of a novel peptide (peptide
      23) that was previously shown to be released from anterior pituitary cells of rat
      in response to growth hormone-releasing hormone. In the pituitary, peptide 23
      isolated from intact cells had an Mr of 31,000, whereas that released into
      culture medium had an Mr of 16,000. Pancreatic islets contained a 19 KD form of
      the peptide. Immunohistochemically, peptide 23 in the rat pituitary gland was
      localized in a subpopulation of somatotropes. In pancreatic islets, the peptide
      was found by triple immunofluorescence labeling to be present in both insulin-
      and somatostatin-containing cells. In the gastrointestinal tract, peptide 23 was
      found only in a subpopulation of endocrine cells in the pyloric glands. This
      subpopulation of cells was found to be entirely separate from those containing
      either serotonin or somatostatin, and may represent one of the other known or as
      yet biochemically uncharacterized cell types in this gland. The results suggest
      that in response to secretagogues in vitro, an altered form of the peptide is
      secreted from pituitary cells and that an intracellular form of peptide 23 is
      expressed in some but not all somatotropes, a large proportion of islet cells,
      and a distinct population of pyloric cells.

PMID- 1348067
TI  - Prevalence of hospital-acquired infections in Spain. EPINE Working Group.
AB  - In May 1990 a prevalence survey of hospital-acquired infections was conducted in
      123 Spanish hospitals, in which 38,489 patients were studied. There was an 8.5%
      prevalence of infected patients and a 9.9% prevalence of infections. The most
      common infections were those of the urinary tract (27.7%), surgical wound (22.7%)
      and lower respiratory tract (15.4%) and bacteraemia (10.6%). There was a 5.9%
      prevalence of patients with surgical wound infection and 3.5% after clean
      surgery. An aetiological diagnosis was made in 58% of the infections. Gram
      negative bacteria were dominant, Escherichia coli (16.3%) and Pseudomonas
      aeruginosa (11.5%) being the most prevalent; 33.8% of the patients were receiving
      antimicrobial agents. The following procedures were shown to be significantly
      associated with hospital-acquired infections: urinary catheterization, parenteral
      nutrition, mechanical ventilation and tracheostomy. The degree of contamination
      during surgery was also a significantly associated risk factor. The survey
      provided extensive information on the distribution of infections and the use of
      antibiotics in clinical services, as well as the differences between hospitals
      according to their size and the presence of certain risk factors.

PMID- 1348068
TI  - Retrospective 6-year study of enterobacter bacteraemia in a Danish university
      hospital.
AB  - In order to study the epidemiology of invasive enterobacter infections, data from
      53 consecutive cases of bacteraemia due to this organism were compared with data
      from 72 randomly selected cases of Escherichia coli bacteraemia. The cases
      occurred among patients admitted to a Danish University hospital over a 6-year
      period. Forty-eight cases were due to Enterobacter cloacae and five were due to
      Ent. aerogenes. Enterobacter bacteraemia was more often of nosocomial origin than
      E. coli bacteraemia and more often polymicrobial. Patients suffering from
      enterobacter bacteraemia were younger than E. coli patients, and males tended to
      predominate. Apart from cancer of the prostate, other malignant diseases tended
      to be more frequent among patients with enterobacter bacteraemia than among E.
      coli patients. Enterobacter bacteraemia was more often associated with a focus in
      central venous catheters and burns, whereas patients with E. coli bacteraemia
      more often showed a focus of infection in the urinary tract. Patients with
      enterobacter bacteraemia and a microbiologically documented focus in the
      respiratory tract or the urinary tract more often had an endotracheal tube or
      indwelling urinary catheter compared to patients with E. coli bacteraemia with a
      similar focus of infection. In patients with no microbiologically documented
      focus enterobacter bacteraemia was more often associated with the presence of
      central and peripheral venous catheters. During the preceding 12 weeks patients
      with enterobacter bacteraemia, more often than E. coli patients, had been treated
      with beta-lactam antibiotics, especially penicillins. The close association with
      devices may indicate that Enterobacter has a special affinity for foreign body
      material. Studies are planned to elucidate this aspect in further detail.

PMID- 1348069
TI  - Spread of Staphylococcus aureus strains of phage-type 95 in Denmark 1968-1989.
AB  - The spread of Staphylococcus aureus strains of phage-type 95 was traced
      retrospectively in Denmark by the review of more than 15,000 S. aureus
      bacteraemia isolates (1957-88) and from data collected by phage-typing of c.
      260,000 isolates from all body sites (1977-89). The first two type 95 strains had
      been isolated from blood in 1968, and after an interval of 3 years there was a
      steady increase of bacteraemia strains all over Denmark. From 1977 to 1989 the
      incidence of type 95 strains among isolates from all body sites increased from
      3.8 to 18.8%. Different patterns of increase were recorded in 13 major hospitals
      and in various clinical departments of two hospitals and these were further
      analysed. Conjunctival swabs gave the highest percentage of type 95 strains and
      those from abscesses gave the lowest percentage. Of the type 95 bacteraemia
      strains 90.4% were resistant to penicillin, but neither methicillin nor
      gentamicin resistance was recorded.

PMID- 1348070
TI  - Clinical isolates of enterococci with high-level resistance to currently
      available aminoglycosides.
AB  - Enterococci isolated from different body sites were tested for high-level
      gentamicin resistance. A total of 139 enterococcal isolates were screened for
      resistance (minimum inhibitory concentration [MIC] greater than 2000 mg l-1) by a
      broth-tube method. Twenty-five (18%) were found to exhibit resistance and this
      was confirmed by agar screening (1000 mg l-1) and agar dilution MIC
      determinations. The majority of isolates also showed high-level resistance to
      kanamycin and streptomycin. The remaining isolates showed high-level resistance
      to gentamicin and kanamycin but not streptomycin. A retrospective clinical review
      was performed. Most patients had a source of definite or likely infection (78%).
      Serious infections such as endocarditis or meningitis were not observed during
      the course of this study. Retrospective clinical data suggest that in cases not
      involving endocarditis or meningitis, neither infection refractory to therapy nor
      relapse of infection is a common sequel to infection with gentamicin-resistant
      enterococci in hospitalized patients.

PMID- 1348071
TI  - Sepsis associated with transhepatic cholangiography.
AB  - A retrospective study was carried out of 74 elderly patients with obstructive
      jaundice undergoing percutaneous transhepatic cholangiography (PTC) and/or
      percutaneous biliary drainage (PBD) in order to assess the effect of prophylactic
      antibiotics on the incidence of fever and sepsis complicating these procedures.
      Seventeen patients underwent PTC alone, while 57 had both PTC and PBD. Fifty
      three patients had either primary or metastatic malignancy. In the other patients
      with benign disease, choledocholithiasis was the most common reason for
      undertaking these procedures. Prophylactic antibiotics were given in 80% of
      cholangiographies and 93% of biliary drainage procedures. There was an overall
      incidence of sepsis of 13.5%. Enterobacter cloacae and Acinetobacter anitratus
      were the most common blood culture isolates in patients with malignant biliary
      obstruction. The incidence of fever was no different between patients who
      underwent PTC alone compared with those who had PTC and PBD. Of 24 patients who
      developed fever, two died secondary to sepsis. Although there was no difference
      in the rate of sepsis and febrile episodes between the two groups, the risk of
      septic episodes and mortality emphasizes the need for antibiotic prophylaxis and
      early therapy in elderly patients undergoing percutaneous biliary drainage
      procedures.

PMID- 1348072
TI  - Question and answer. Disinfecting endoscopes.

PMID- 1348073
TI  - Surgery and face masks in Sweden.

PMID- 1348074
TI  - Face masks and postoperative infection.

PMID- 1348075
TI  - Masks in surgery.

PMID- 1348076
TI  - Relapse of Salmonella infection after ciprofloxacin.

PMID- 1348077
TI  - A simple lysis method for the culture of dialysis fluid from patients on
      continuous ambulatory peritoneal dialysis.

PMID- 1348078
TI  - Methicillin-resistant Staphylococcus aureus from Europe.

PMID- 1348079
TI  - Recombinant interferon-alpha for chronic hepatitis C in patients positive for
      antibody to human immunodeficiency virus. Comite des Anti-Viraux.
AB  - To assess the response to and tolerance of recombinant interferon-alpha
      administration in patients with chronic hepatitis C and human immunodeficiency
      virus (HIV) infection, 12 patients with chronic hepatitis C and HIV infection
      were given interferon-alpha, 1, 3, or 5 million units thrice weekly, for 4 or 6
      months. Four patients had a complete response (normal serum alanine
      aminotransferase activity [ALT]), 3 had a near-complete response (serum ALT less
      than one-and-one-half times the upper limit of normal), and 5 had no response at
      the end of administration. Histologic examination of liver showed an improvement
      in 1 patient with complete response and no improvement in another patient with no
      response. In patients with chronic hepatitis C with HIV infection, the response
      to and tolerance of recombinant interferon-alpha were not different from those
      usually observed in patients with chronic hepatitis C infection without HIV
      infection.

PMID- 1348080
TI  - Human hematopoietic cells and thymic epithelial cells induce tolerance via
      different mechanisms in the SCID-hu mouse thymus.
AB  - To study the role of thymic education on the development of the human T cell
      repertoire, SCID-hu mice were constructed with fetal liver and fetal thymus
      obtained from the same or two different donors. These animals were studied
      between 7 and 12 mo after transplantation, at which times all thymocytes and
      peripheral T cells were derived from stem cells of the fetal liver graft.
      Immunohistology of the thymus grafts demonstrated that thymic epithelial cells
      were of fetal thymus donor (FTD) origin. Dendritic cells and macrophages of fetal
      liver donor (FLD) origin were abundantly present in the medullary and cortico
      medullary areas. Thymocytes of SCID-hu mice transplanted with liver and thymus of
      two different donors (FLDA/FTDB animals) were nonresponsive to Epstein-Barr virus
      transformed B cell lines (B-LCL) established from both the FLDA and FTDB, but
      proliferated vigorously when stimulated with third-party allogeneic B-LCL. Mixing
      experiments showed that the nonresponsiveness to FTDB was not due to suppression.
      Limiting dilution analysis revealed that T cells reacting with the human
      histocompatibility leukocyte antigens (HLA) of the FLD were undetectable in the
      CD8+ T cell population and barely measurable in the CD4+ subset. On the other
      hand, CD4+ and CD8+ T cells reactive to the HLA antigens of the FTD were readily
      detectable. These results indicate that FLD-reactive cells were clonally deleted,
      whereas FTD-reactive cells were not. However, the frequencies of FTD-reactive T
      cells were consistently twofold lower than those of T cells specific for any
      third-party B-LCL. In addition, the cytotoxic activity and interleukin 2
      production by FTD-specific T cells were lower compared with that of third-party
      reactive T cell clones, suggesting that FTD-specific cells are anergic. These
      data demonstrate that T cells become tolerant to autologous and allogeneic HLA
      antigens expressed in the thymus via two different mechanisms: hematopoietic
      cells present in the thymus induce tolerance to "self"-antigens by clonal
      deletion, whereas thymic epithelial cells induce tolerance by clonal energy and
      possibly deletion of high affinity clones.

PMID- 1348082
TI  - The effects of chronic infection with a superantigen-producing virus.
AB  - C3H/HeJ mice transmit a mouse mammary tumor virus from mother to pup in milk. The
      retrovirus infects mice shortly after birth and, when expressed in recipient
      mice, produces a V beta 14-specific superantigen. The consequences of such
      expression on V beta 14-bearing T cells are examined in this paper. Most cells
      bearing V beta 14 and either CD4 or CD8 are eliminated in the thymus. Some V beta
      14-bearing cells escape to the periphery, however. Those bearing CD8 are
      unaffected by expression of the viral superantigen. The percentage of peripheral
      CD4+ T cells bearing V beta 14 drops with time after birth. In large part this
      seems to be due to the fact that many of these cells become anergic because of
      exposure to the viral superantigen. Unlike normal T cells, these anergic cells
      cannot undergo peripheral postthymic expansion. Consequently, they drop in
      percentage even during a time when their total numbers are constant.

PMID- 1348081
TI  - Identification of a novel surface protein on activated CD4+ T cells that induces
      contact-dependent B cell differentiation (help).
AB  - CD4+ T lymphocytes provide contact-dependent stimuli to B cells that are critical
      for the generation of specific antibody responses in a process termed T helper
      function. The surface structures on activated CD4+ T cells that mediate this
      function are not fully known. We previously reported the isolation of a
      functionally unique subclone of the Jurkat leukemic T cell line (D1.1) that
      constitutively expressed contact-dependent helper effector function. To identify
      T cell surface molecules that mediate contact-dependent T helper function, a
      monoclonal antibody (mAb), designated 5c8, was generated that inhibits D1.1
      mediated B cell activation and immunoprecipitates a novel 30-kD protein structure
      from surface-iodinated D1.1 cells. Normal CD4+ T cells express 5c8 antigen (Ag)
      transiently 5-6 h after activation by phorbol myristate acetate and
      phytohemagglutinin with maximal expression 5-6 h after activation and absence of
      expression by 24 h. In contrast, neither resting nor activated CD8+ T cells
      express 5c8 Ag. In functional studies, mAb 5c8 inhibits the ability of fixed,
      activated CD4+ T cells to induce B cell surface CD23 expression. In addition, mAb
      5c8 inhibits the ability of CD4+ T cells to direct terminal B cell
      differentiation driven by pokeweed mitogen. Taken together, these data suggest
      that 5c8 Ag is a novel, activation-induced surface T cell protein that is
      involved in mediating a contact-dependent element of the helper effector function
      of CD4+ T lymphocytes.

PMID- 1348083
TI  - T cell receptor V alpha-V beta repertoire and cytokine gene expression in active
      multiple sclerosis lesions.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system with presumed autoimmune etiology. A recent study has suggested the
      presence of a restricted T cell receptor (TCR) V alpha repertoire in MS lesions.
      The presence of such a restricted TCR repertoire at the site of inflammation
      would have important consequences for the pathogenesis and the ultimate treatment
      of MS. To further characterize the TCR V alpha and V beta repertoire in MS plaque
      tissue, we examined a series of 26 histologically well-characterized central
      nervous system (CNS) tissue specimens from six MS patients as well as samples
      from five normal postmortem cases and a case of subacute sclerosing
      panencephalitis. RNA was extracted from frozen sections and cDNAs were amplified
      by polymerase chain reaction using primers for TCR V alpha (V alpha 1-18) and V
      beta (V beta 1-19) gene families. This analysis demonstrated a broad TCR V alpha
      V beta repertoire in active lesions, while fewer TCR V genes were detected in
      chronic plaques and control samples. Even though a large number of TCR V alpha
      and V beta gene segments were present in the majority of active lesions, there
      were clear differences in the TCR repertoire between plaques from the same case,
      suggesting that local events influence the TCR repertoire at the level of T cell
      recruitment or T cell expansion. Examination of cytokine mRNAs demonstrated that
      IL-1 mRNA was present in the majority of acute and subacute plaques, while IL-2
      and IL-4 mRNA were detected in only a few acute lesions. These data demonstrate
      that the TCR repertoire in MS plaques is polyclonal. However, autoreactive
      alpha/beta T cells thought to be critical in the initiation of the inflammatory
      process probably represent a minor fraction of T cells in active MS plaques and
      may use a limited number of TCR V gene segments for recognition of the
      autoantigen.

PMID- 1348084
TI  - Differential activation of GABAA and GABAB receptors by spontaneously released
      transmitter.
AB  - 1. Whole-cell patch-clamp techniques were used to record from dentate gyrus
      granule cells in adult rat brain slices when N-methyl-D-aspartate (NMDA) and non
      NMDA type glutamate receptors were blocked by D-2-amino-5-phosphonovaleric acid
      (D-AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively.
      Spontaneous inhibitory postsynaptic currents (sIPSCs), each presumably due to
      vesicular release of gamma-aminobutyric acid (GABA), selectively activated GABAA
      type receptors. None of the individual sIPSCs showed a slow-onset potassium
      current characteristic of GABAB receptor activation. 2. In contrast, stimulation
      in the molecular layer with a bipolar stimulating electrode or bath application
      of the convulsant drug 4-aminopyridine (4-AP, 10-30 microM) elicited fast GABAA
      IPSCs followed by slower outward currents that were sensitive to the selective
      GABAB antagonist CGP 35348 (0.1-1 mM) and that reversed polarity near the
      potassium equilibrium potential. 3. CGP 35348 (0.5-1 mM) or the GABAB agonist (
      )baclofen (1 microM) had no significant effect on the frequency or average
      amplitude of sIPSCs. However, either bath application of (-)baclofen (1 microM)
      or a preceding conditioning stimulus caused large reductions in the amplitude of
      stimulus-evoked IPSCs, suggesting a strong GABAB-mediated presynaptic inhibition
      of stimulus-evoked GABA release. 4. We conclude that under normal conditions
      spontaneous transmitter release does not activate GABAB receptors in dentate
      gyrus slices. These findings are consistent with either of two general
      possibilities. Separate groups of interneurons with different basal firing rates
      may selectively form GABAA and GABAB synapses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348085
TI  - Modulation of extracellular pH by glutamate and GABA in rat hippocampal slices.
AB  - 1. Alkaline extracellular pH transients evoked by afferent stimulation, and local
      pressure ejection of glutamate and gamma-aminobutyric acid (GABA), were studied
      in the CA1 region of rat hippocampal slices. Amino acid-evoked responses were
      obtained by use of a dual micromanipulator, with the tip of a double-barreled pH
      sensitive microelectrode positioned 50 microns from a pressure ejection pipette.
      2. At 31 degrees C, in Ringer solutions buffered with 26 mM HCO3- and 5% CO2,
      mean extracellular pH in submerged 300-microns slices was 7.15 +/- 0.12 (n = 27
      slices), at a tissue depth of approximately 150 microns. In Ringer buffered with
      35 mM HCO3- and 5% CO2, extracellular pH was 7.29 +/- 0.10 (n = 19 slices). 3.
      Repetitive stimulation of the Schaffer collaterals caused an extracellular
      alkaline shift in stratum oriens, pyramidale, and radiatum, averaging 0.05 +/-
      0.03 pH units among all regions (n = 138), with a maximum response of 0.16 pH
      units. Alkaline transients of similar appearance were obtained by local ejection
      of glutamate (0.01-0.12 pH units, n = 110) and GABA (0.01-0.18 pH units, n =
      137). Control ejection of these amino acids into dilute agar caused only small
      acid shifts. 4. Superfusion of 100 microM picrotoxin abolished the GABA-evoked
      alkaline shift but failed to inhibit the Schaffer collateral- and glutamate
      evoked alkalinizations. 5. Superfusion of 10(-5)-10(-3) M acetazolamide acidified
      the baseline by 0.05-0.10 pH units and amplified the Schaffer collateral- and
      glutamate-evoked alkaline shifts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348086
TI  - Single-electrode voltage-clamp analysis of the N-methyl-D-aspartate component of
      synaptic responses in neocortical slices from children with intractable epilepsy.
AB  - 1. Synaptic transmission mediated by the N-methyl-D-aspartate (NMDA)-receptor
      type was studied in neocortex from children undergoing surgical treatment for
      intractable epilepsy. Intracellular recordings from pyramidal cells were obtained
      in slices of neocortical tissue by use of microelectrodes. Synaptic responses
      were induced by electrical stimulation and studied with current-clamp and single
      electrode voltage-clamp techniques. The NMDA-receptor-mediated component of the
      synaptic responses was isolated by addition of 10 microM bicuculline and 30
      microM 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) in the perfusion solution.
      2. In the presence of bicuculline and CNQX, electrical stimulation evoked an
      excitatory postsynaptic potential (EPSP) in every recorded cell. The amplitude of
      this EPSP increased when membrane potential was depolarized with injected
      current. 3. All cells studied in voltage clamp were recorded with microelectrodes
      containing Cs+ and QX 314. To avoid contamination of the responses from voltage
      dependent Ca2+ conductances, membrane potential was held at depolarized
      potentials until Ca2+ spiking inactivated completely. The evoked excitatory
      postsynaptic currents (EPSCs) measured at resting membrane potential ranged from
      100 to 400 pA. The NMDA receptor-selective antagonist DL-2-amino-5
      phosphonopentanoic acid (AP-5) reversibly decreased the current amplitude by 60%
      for 10 microM and 80% for 30 microM. 4. The current-voltage (I-V) relation showed
      a region of negative slope conductance between -100 and -20 mV. The largest
      currents (-250 to -900 pA) were recorded in the range of -45 to -20 mV and
      reversed between -10 and +10 mV. Removing Mg2+ from the perfusion solution
      decreased the negativity of the slope, which is consistent with a reduction in
      the voltage-dependent Mg2+ block of the NMDA-receptor channel. 5. The I-V plots
      obtained from cells recorded in the most abnormal tissue were averaged and
      compared with those from the least abnormal tissue. No significant difference was
      found between these two groups. The averaged plots from the youngest patients (8
      and 10 mo old) and those from the oldest (5-15 yr old) patients were also
      compared, and the results from these two groups were not significantly
      different.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1348087
TI  - Highlights from the Second Sino-American Nuclear Medicine Conference, Beijing,
      China [congress].

PMID- 1348088
TI  - The laparoscope and the undescended testis.
AB  - An empty scrotum with an impalpable testis/testes presents a difficult diagnostic
      and therapeutic problem. Many methods have been used in an attempt at, or as an
      aid to, the localization of these gonads including venography, ultrasonography,
      hormone manipulation, and surgical exploration. Laparoscopy has been recommended
      as an aid to diagnosis. We reviewed our experience with the laparoscope in the
      diagnosis and management of this problem over a 7-year period. Laparoscopy
      permitted planning of the approach to orchidopexy, depending on whether the
      vessels entered the deep inguinal ring. In the latter group 48% of the testes
      were found to be atrophic. We also found the laparoscope to be of value in
      performing the first stage of the Fowler-Stephens long loop vas orchidopexy in
      three cases, with long-term viability of the testes in two of these.

PMID- 1348089
TI  - Dopaminergic and serotonergic activities of imidazoquinolinones and related
      compounds.
AB  - The synthesis of 5-(dipropylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij] quinolin
      2(1H)-one (5), a potent dopamine D2 agonist showing high dopamine/serotonin
      (5HT1A) selectivity, is described. Dopaminergic activity is associated with the
      (R)-enantiomer of 5; the (S)-enantiomer shows no dopaminergic activity. A series
      of analogues where the imidazolone ring was modified to various 5- or 6-membered
      heterocyclic rings were prepared. Some of these compounds showed a combination of
      dopaminergic and serotonergic activity, while one compound, 6-(dipropylamino)
      1,2,6,7-tetrahydro-3H,5H-pyrido[3,2,1- ij]quinazolin-3-one (24), was a selective
      serotonergic agonist. Various analogues of 5 where the dipropylamine substituent
      was modified were prepared. Most of these showed reduced dopaminergic activity,
      while several were as potent as 5 at the serotonin 5HT1A receptor. Orientations
      for the new compounds at dopamine and serotonin receptors are proposed and
      compared with those of other tricyclic ligands known to have high affinity at
      these receptors.

PMID- 1348090
TI  - Noncataleptogenic, centrally acting dopamine D-2 and serotonin 5-HT2 antagonists
      within a series of 3-substituted 1-(4-fluorophenyl)-1H-indoles.
AB  - A series of 1-(4-fluorophenyl)-1H-indoles substituted at the 3-position with 1
      piperazinyl, 1,2,3,6-tetrahydro-4-pyridinyl, and 4-piperidinyl was synthesized.
      Within all three subseries potent dopamine D-2 and serotonin 5-HT2 receptor
      affinity was found in ligand binding studies. Quipazine-induced head twitches in
      rats were inhibited by most derivatives as a measure of central 5-HT2 receptor
      antagonism. Piperazinyl and tetrahydropyridyl indoles were cataleptogenic, while
      piperidyl substituted indoles surprisingly were found to be noncataleptogenic or
      only weakly cataleptogenic. Noncataleptogenic piperidyl derivatives also failed
      to block dopaminergic-mediated stereotypies, that is methyl phenidate-induced
      gnawing behavior in mice. These profiles resemble that of the atypical
      neuroleptic clozapine. 1-Ethyl-2-imidazolidinone was found to be the optimal
      substituent of the basic nitrogen atom in order to avoid catalepsy. The atypical
      neuroleptic 1-[2-[4-[5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl]-1-piperidinyl]
      ethyl]-2-imidazolidinone (sertindole, compound 14c) was selected for further
      development as a result of these structure/activity studies.

PMID- 1348091
TI  - Prenatal prediction of spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is a common cause of inherited morbidity and
      mortality in childhood. The wide range of phenotypes in SMA, uncertainty
      regarding its mode of inheritance, and the suggestion of linkage heterogeneity
      have complicated the genetic counselling of parents of affected children. The
      locus responsible for autosomal recessive SMA has been mapped to 5q11.2-q13.3.
      The most likely order of loci is cen-D5S6-(SMA,D5S125)-(JK53CA1/2,D5S112)-D5S3 9
      qter, with highly polymorphic loci being identified at JK53CA1/2 and D5S39. We
      describe linkage studies with another highly polymorphic locus, D5S127, that is
      closely linked to D5S39. This genetic map can be used as the basis for genetic
      counselling in families with autosomal recessive SMA. Appropriate allowance can
      be made for sporadic cases owing to non-inherited causes and for linkage
      heterogeneity or misdiagnoses.

PMID- 1348092
TI  - Prenatal prediction of Werdnig-Hoffmann disease using linked polymorphic DNA
      probes.
AB  - Werdnig-Hoffmann disease is a common autosomal recessive neuromuscular disorder
      that results in paralysis and death. No treatment to prevent this disease or to
      alter its unremitting course has been found. Recently, linkage analysis with
      cloned DNA probes has shown that the mutation causing Werdnig-Hoffmann disease is
      located on chromosome 5q12-q14. We performed genetic analysis for the prenatal
      diagnosis of Werdnig-Hoffmann disease in seven at risk families. Two fetuses were
      diagnosed as being affected and the remainder as unaffected, and this was
      confirmed after birth. This study shows that prenatal diagnosis of Werdnig
      Hoffmann disease has become feasible.

PMID- 1348093
TI  - Prenatal diagnosis and presymptomatic detection of neurofibromatosis type 1.
AB  - A two year experience of DNA diagnosis for NF1 is presented. Twenty-three NF1
      families have been analysed using 11 closely linked and intragenic markers.
      Prenatal testing was undertaken for six families; 11 affected subjects and their
      partners wished to know if they would be informative for future prenatal testing,
      seven of whom are so far fully informative. Presymptomatic testing was done for
      six subjects. Despite the availability of a series of closely linked markers,
      informativeness could not be achieved in all of the families tested.

PMID- 1348094
TI  - Clinical variability of type 1 neurofibromatosis: is there a neurofibromatosis
      Noonan syndrome?
AB  - Detailed clinical, ophthalmological, and molecular studies were performed on a
      multigeneration family in which there were many subjects with type 1
      neurofibromatosis, a common autosomal dominant disorder. Affected family members
      displayed a wide range of clinical findings including, in two subjects, features
      seen in Noonan syndrome (triangular facies, downward slanting palpebral fissures,
      micrognathia, short stature, and learning disability). Subjects have been
      described previously whose features have overlapped with neurofibromatosis and
      Noonan syndrome, and it has been suggested that these persons might represent a
      separate condition. DNA haplotype analysis showed linkage of the
      neurofibromatosis phenotype seen in this family to the proximal long arm of
      chromosome 17 in the region where the type 1 neurofibromatosis gene has been
      mapped. These results imply that the Noonan phenotype seen in some patients with
      type 1 neurofibromatosis might be the result of variable or variant expression of
      the neurofibromatosis gene on chromosome 17. The possible role of non-specific
      factors, such as fetal hypotonia, in producing the neurofibromatosis-Noonan
      phenotype needs further investigation. The availability of closely linked and
      intragenic molecular markers for neurofibromatosis could potentially be useful in
      the diagnosis and characterisation of patients and families with atypical forms
      of neurofibromatosis.

PMID- 1348096
TI  - Psychotropic drug use in the nursing home.

PMID- 1348095
TI  - Absence of linkage of Noonan syndrome to the neurofibromatosis type 1 locus.
AB  - Eleven families with Noonan syndrome in either two or three generations have been
      identified. Following the reports of subjects with features of both Noonan
      syndrome and neurofibromatosis type 1, these pedigrees have been studied using a
      number of probes at the neurofibromatosis type 1 locus (17q11). A significantly
      negative lod score was obtained with the intragenic probe NF1-C2, suggesting that
      the genes for Noonan syndrome and neurofibromatosis type 1 are not contiguous.

PMID- 1348097
TI  - [Millions of refugees. Handling programs for improvement of refugees' mental
      health is a target of an international conference].

PMID- 1348098
TI  - [International meeting on hernia surgery: mesh facilitates healing].

PMID- 1348099
TI  - Effect of the D2-autoreceptor agonist B-HT 958 on both spontaneous and ACTH
      induced stretching, yawning and grooming in the rat.
AB  - The D2 autoreceptor agonist B-HT 958, intraperitoneally injected into Wistar male
      rats in a novel environment, significantly increased stretching and yawning (SY)
      while inhibiting grooming. Pretreatment with the D2 antagonist sulpiride reversed
      these effects, antagonizing SY and restoring grooming. Similarly, when B-HT 958
      was administered to rats in their home cages, it elicited SY and abolished
      grooming; moreover, when administered before the i.c.v. injection of
      adrenocorticotropin hormone, dose-dependently enhanced SY and strongly
      antagonized the typical syndrome of intensified grooming induced by the peptide.
      The possible relationship between SY and grooming and the involvement of D2
      autoreceptors are discussed.

PMID- 1348100
TI  - CooB is required for assembly but not transport of CS1 pilin.
AB  - CS1 pili are filamentous proteinaceous appendages found on many enterotoxigenic
      Escherichia coli (ETEC) strains isolated from human diarrhoeal disease. They are
      thought to effect colonization of the upper intestine by facilitating binding to
      human ileal epithelial cells. We have identified a gene, cooB, which lies
      directly upstream of cooA, the gene that encodes the major structural CS1
      protein. When translated in vitro, the protein product of cooB migrates in sodium
      dodecyl sulphate/polyacrylamide gel with an apparent molecular mass of 26 kDa,
      which is consistent with that predicted from its DNA sequence. We constructed a
      mutant allele (cooB-1) by insertion of the omega fragment, which inhibits
      transcription and translation, into the cooB gene in vitro. In a derivative of an
      ETEC strain with the cooB-1 mutation (JEF100) and a plasmid that encodes Rns
      (pEU2030), the positive regulator required for CS1 expression, no cooB and a
      greatly reduced level of cooA product was detectable in total cell extracts. The
      reduction of cooA in this strain appears to result from polarity of the cooB
      mutation because introduction of the wild-type cooA gene in trans causes
      production of CooA protein, which is found in cell pellet extracts, in extracts
      containing only surface proteins and in the culture supernatant. Therefore, in
      the absence of CooB, CooA is stable and it is transported through both inner and
      outer membranes. However, the cooB-1 strain with cooA in trans does not cause
      haemagglutination of bovine erythrocytes (the model system used to assay
      adherence mediated by coli surface antigen 1 (CS1) pili).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1348102
TI  - DNA restriction enzymes and RFLPs in medicine.

PMID- 1348101
TI  - Cloning of a yeast gene coding for the glutamate synthase small subunit (GUS2) by
      complementation of Saccharomyces cerevisiae and Escherichia coli glutamate
      auxotrophs.
AB  - A Saccharomyces cerevisiae glutamate auxotroph, lacking NADP-glutamate
      dehydrogenase (NADP-GDH) and glutamate synthase (GOGAT) activities, was
      complemented with a yeast genomic library. Clones were obtained which still
      lacked NADP-GDH but showed GOGAT activity. Northern analysis revealed that the
      DNA fragment present in the complementing plasmids coded for a 1.5kb mRNA. Since
      the only GOGAT enzyme so far purified from S. cerevisiae is made up of a small
      and a large subunit, the size of the mRNA suggested that the cloned DNA fragment
      could code for the GOGAT small subunit. Plasmids were purified and used to
      transform Escherichia coli glutamate auxotrophs. Transformants were only
      recovered when the recipient strain was an E. coli GDH-less mutant lacking the
      small GOGAT subunit. These data show that we have cloned the structural gene
      coding for the yeast small subunit (GUS2). Evidence is also presented indicating
      that the GOGAT enzyme which is synthesized in the E. coli transformants is a
      hybrid comprising the large E. coli subunit and the small S. cerevisiae subunit.

PMID- 1348103
TI  - [Histological and biological evaluation of preoperative radiotherapy on T1N0
      breast carcinoma].
AB  - In order to clarify the role of radiotherapy in breast preserving surgery for
      early breast cancer, histological and biological effects of preoperative
      radiation were evaluated. Thirty-five T1N0 patients were treated by preoperative
      radiotherapy with beta-tron, cumulative doses of which were ranging from 25 Gy (5
      Gy x 5) to 40 Gy (8 Gy x 5) and underwent subsequent modified radical mastectomy
      2 or 3 weeks after the termination of radiotherapy. Clinical tumor shrinkage more
      than 50% was observed in 25 out of 35 cases (71%) but did not directly correlate
      with histological effects. Radiotherapy was basically ineffective within 25-30
      Gy, whereas histological effects more than Grade 2 were gained in 8 out of 25
      patients (32%), who had received 40 Gy or more. In the preoperative radiation
      group, there were more ER(+), PgR(+) and histologically well-differentiated cases
      than in the non-radiated stage I patients. Mitotic figures were also
      significantly reduced after radiotherapy, whereas the expression of c-erB-2
      protein was unchanged between these two groups. Our data indicate the various
      radiosensitivity of breast cancer cells and the indication of hormone therapy for
      the conservative treatment of breast carcinoma.

PMID- 1348104
TI  - [The evaluation of proliferating activity in gastric carcinoma stained by
      proliferating cell nuclear antigen (PCNA): preliminary report].

PMID- 1348106
TI  - P-glycoprotein expression and prognosis of neuroblastoma.

PMID- 1348105
TI  - Characterization of the F plasmid bifunctional conjugation gene, traG.
AB  - The Escherichia coli F plasmid gene, traG, is required for two stages of the
      conjugation process: pilus biosynthesis and mating aggregate stabilization. The
      nucleotide sequence of traG has been determined and the topology of its product
      in the cytoplasmic membrane analysed using protease accessibility experiments.
      Complementation analysis employing plasmid deletions revealed a correlation
      between an N-terminal periplasmic segment of the protein product (TraGp) and its
      pilus assembly activity. Production of an anti-TraGp antiserum has facilitated
      the detection of TraGp*, a possible internal cleavage product of TraGp. Although
      its function is unknown. TraGp* is located in the periplasm and has been shown to
      possess sequences required for aggregate stabilization. The detection of TraGp*
      raises the possibility that the two functions of traG are carried out by separate
      products.

PMID- 1348107
TI  - P pili in uropathogenic E. coli are composite fibres with distinct fibrillar
      adhesive tips.
AB  - Escherichia coli is a frequent cause of several common bacterial infections in
      humans and animals, including urinary tract infections, bacteraemia and bacteria
      related diarrhoea and is also the main cause of neonatal meningitis. Microbial
      attachment to surfaces is a key event in colonization and infection and results
      mainly from a stereochemical fit between microbial adhesins and complementary
      receptors on host cells. Bacterial adhesins required for extracellular
      colonization by Gram-negative bacteria are often minor components of
      heteropolymeric fibres called pili which must be oriented in an accessible manner
      in these structures to be able to bind to specific receptor architectures. P pili
      mediate the binding of uropathogenic E. coli to a digalactoside receptor
      determinant present in the urinary tract epithelium. We report here that the
      adhesin is a component of distinct fibrillar structures present at the tips of
      the pili. These virulence-associated tip fibrillae are thin, flexible polymers
      composed mostly of repeating subunits of PapE that frequently terminate with the
      alpha-D-galactopyranosyl-(1-4)-beta-D-galactopyranose or Gal alpha (1-4)Gal
      binding PapG adhesin.

PMID- 1348108
TI  - Antioxidant effect on renal scarring following infection of mannose-sensitive
      piliated bacteria.
AB  - Renal scars have been considered to occur in later stages of chronic
      pyelonephritis. In our experimental pyelonephritis model, bacteria which
      possessed mannose-sensitive (MS) pili on the surface promoted renal scarring
      following inoculation to the renal parenchyma. Polyethylene glycol-modified
      superoxide dismutase (PEG-SOD) and 2-O-octadecylascorbic acid (CV3611)
      significantly suppressed scarring when administered orally or parenterally during
      the early stage of kidney infection with MS-piliated bacteria. These findings
      suggest that the superoxide and other active oxygens play an important role in
      renal scarring following infection and that PEG-SOD and CV3611 may be agents
      capable of preventing renal scarring following bacterial pyelonephritis.

PMID- 1348109
TI  - The effect of baclofen and somatostatin on neuronal activity in the rat
      ventromedial hypothalamic nucleus in vitro.
AB  - The electrical properties of neurones within the ventromedial hypothalamic
      nucleus of the rat were studied in an in vitro slice preparation, using
      conventional intracellular recording techniques. A detailed analysis of 36
      intracellular recordings appeared to suggest 3 cell types, based on membrane
      capacitance and resistance characteristics, confirming previous reports of a
      diversity of cell types within this nucleus. The responsiveness of each cell type
      to exogenously-applied baclofen and somatostatin was also investigated. The
      inhibitory responses to both of these drugs were concentration-related (over the
      range 100 nM to 1 microM), tetrodotoxin-resistant and consisted of a membrane
      hyperpolarization (mean +/- SEM = 6.7 +/- 1 and 10.7 +/- 1 mV for 1 microM
      somatostatin and baclofen, respectively) and an associated reduction in the
      firing frequency of spontaneously active cells. These agonist-evoked responses
      probably represented direct postsynaptic actions but they were not restricted to
      any single type of cell. Evidence for an additional presynaptic effect of
      baclofen was also obtained. Responses to baclofen were extremely robust and
      readily quantifiable, whereas those to somatostatin showed pronounced long
      lasting desensitization, which was particularly marked a larger concentrations.
      These data support previous contentions, based on in vivo studies, that
      somatostatin and GABA are likely to participate in the control of complex
      functions by the ventromedial hypothalamic nucleus.

PMID- 1348110
TI  - Modulation of release of acetylcholine from the striatum by a proposed excitatory
      amino acid antagonist U-54494A: comparison with known antagonists, diazepam and
      phenytoin.
AB  - The effect of (U-54494A) cis-3,4-dichloro-N-methyl-N-[2-(1-Pyrrolidinyl)-
      cyclohexyl] benzamide monohydrochloride, an excitatory amino acid antagonist, on
      N-methyl-D-aspartic acid (NMDA)- and K(+)-evoked release of [3H]acetylcholine [(
      3H]ACh) from slices of striatum was investigated. For the purpose of comparison,
      MK 801, PCP, CGP 37849, CPP, phenytoin and diazepam were investigated under
      identical conditions. Both U-54494A and the excitatory amino acid antagonists
      blocked NMDA-evoked release of [3H]ACh but these compounds failed to inhibit K(+)
      evoked release of this neurotransmitter. Phenytoin blocked both NMDA and K(+)
      evoked release of [3H]ACh, whereas diazepam was ineffective under similar
      conditions. These observations indicate that excitatory amino acid antagonists,
      including U-54494A, may mediate their anticonvulsant effect by blocking the
      activity of NMDA receptors, diazepam by activating the benzodiazepine receptors
      and phenytoin by inhibiting the activity of various depolarizing agents.

PMID- 1348111
TI  - The effect of phencyclidine and DL-2-amino-5-phosphonovaleric acid on N-methyl-D
      aspartic acid induced changes in extracellular concentration of dopamine and
      DOPAC in the rat neostriatum.
AB  - The effects of N-methyl-D-aspartic acid (NMDA) and phencyclidine (PCP) on
      extracellular levels of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) in
      the striatum of the rat were studied using in vivo microdialysis. Intrastriatal
      infusion of NMDA produced a significant dose-dependent increase in extracellular
      DA and a decrease in concentrations of DOPAC. Whereas both 2-amino-5
      phosphonovalerate (APV) and PCP antagonized the NMDA-induced increase in
      extracellular levels of DA, the effect on NMDA-induced changes in extracellular
      concentrations of DOPAC were different for the two compounds. The APV
      significantly attenuated the decrease in extracellular DOPAC produced by smaller
      concentrations of NMDA, whereas PCP did not prevent decrease in DOPAC produced by
      any concentrations of NMDA. Phencyclidine alone produced a dose-dependent
      increase in extracellular DA but had no effect on the extracellular concentration
      of DOPAC. This study demonstrated that PCP, at concentrations which did not
      produce an increase in extracellular DA, antagonized the effect of the NMDA on
      DA. The data also indicated that both APV and PCP antagonized the NMDA-evoked
      release of DA over a range of concentrations of NMDA, even though they did so by
      different mechanisms.

PMID- 1348112
TI  - Neuroendocrinological and neurochemical effects of sigma ligands.
AB  - The potential antipsychotic agents BMY 14802, remoxipride, tiospirone and
      gevotriline (WY 47,384) have a relatively high affinity for sigma binding sites
      in brain tissue. In the present study, the effects of these sigma ligands on
      concentrations of prolactin and corticosterone in serum in the rat were
      investigated. In addition, the effects of these agents on the synthesis and/or
      release of dopamine from tuberoinfundibular and nigrostriatal neurons were
      determined. Concentrations of prolactin and corticosterone in serum were
      increased dose-dependently by BMY 14802, tiospirone, remoxipride and gevotriline.
      The activity of tyrosine hydroxylase within the terminals of tuberoinfundibular
      dopamine neurons in vivo also was increased by BMY 14802, tiospirone and
      gevotriline, but not by remoxipride. The extracellular concentrations of dopamine
      and dihydroxyphenylacetic acid in the striatum, as determined by in vivo
      microdialysis, were increased by BMY 14802 (5-20 mg/kg, s.c.) and remoxipride (3
      mg/kg, s.c.). These data suggest the involvement of sigma receptors in the
      regulation of secretion of prolactin and corticosterone, as well as the activity
      of tuberoinfundibular and nigrostriatal dopamine neurons. Moreover, the pattern
      of neurochemical and neuroendocrinological responses to these sigma ligands
      resembled those which have been determined previously for atypical antipsychotics
      and support the contention that these sigma ligands may be antipsychotic agents
      with an atypical profile of action.

PMID- 1348113
TI  - The effects of dexmedetomidine, an alpha 2 agonist, on learning and memory,
      assessed using passive avoidance and water maze tasks in rats.
AB  - The effects of dexmedetomidine, a specific and potent alpha 2 agonist, on the
      performance of rats in passive avoidance and water maze tasks were studied. Pre
      training administration of subanaesthetic dose (9.0 micrograms/kg) of
      dexmedetomidine impaired the retention of the passive avoidance task (assessed 24
      hr after training) but it did not affect the training of this task. Smaller doses
      (0.3, 0.9 and 3.0 micrograms/kg) did not affect the training or retention of this
      aversively motivated task. On the other hand, pre-training administration of 0.3
      and 0.9 microgram/kg dexmedetomidine impaired the acquisition of the water maze
      task, whereas larger doses (3.0 and 9.0 micrograms/kg) had no significant effect
      on spatial learning. Pre-training administration of dexmedetomidine (0.3-9.0
      micrograms/kg) increased swimming speed in rats. Only a large dose (300
      micrograms/kg) of dexmedetomidine, administered immediately after training,
      impaired the retention of the passive avoidance task and the acquisition of the
      water maze task. These data agree with previous findings that pharmacological
      manipulation of the noradrenergic system affects the retention of aversively
      motivated (passive avoidance) tasks. The present results suggest that the dose
      response curve of dexmedetomidine for impairment of learning/memory differs
      between the passive avoidance and water maze tasks.

PMID- 1348114
TI  - Foreshortening of the inferior conjunctival fornix associated with chronic
      glaucoma medications.
AB  - The authors designed a device to measure the depth of the inferior conjunctival
      fornix at the slit lamp using topical anesthesia. The fornices of 179 glaucoma
      patients receiving topical medications for glaucoma and 420 control subjects who
      had no history of ocular disease were measured. These measurements were age
      stratified by decade. A significant foreshortening of the inferior conjunctival
      fornix was found with aging (P less than 0.01). Patients in their sixth through
      ninth decades using miotics for 3 years or longer and patients using nonmiotic
      agents for 3 years or longer exhibited significant foreshortening of the inferior
      fornix when compared with age-stratified (by decade) control subjects (P less
      than 0.01). These observations suggest that increasing age and topical
      medications for glaucoma, or the preservatives, used for 3 years or longer, are
      independently associated with conjunctival shrinkage.

PMID- 1348115
TI  - Reactive synaptogenesis following degeneration of photoreceptor terminals in the
      fly's optic lobe: a quantitative electron microscopic study.
AB  - Following photo-ablation of receptor cells in the retina of the housefly's
      compound eye, their synaptic terminals degenerate with a timecourse which we have
      followed over 8 d. Degeneration deprives the monopolar interneurons in the first
      optic neuropile, the lamina, of their main synaptic input. Simultaneously it
      deprives one monopolar interneuron (L2) of one of its synaptic targets, as L2
      makes numerous feedback synaptic contacts at which it is pre-synaptic upon
      receptor terminals. Because the feedback synapses are dyadic, input still remains
      available to the second element post-synaptic at the dyad, which does not
      degenerate. This element is T1, a higher-order interneuron from the next most
      proximal neuropile (the medulla). Some of the original feedback synaptic sites
      soon disappear as a consequence of the photo-ablation, but their loss is partly
      offset by the production of new synaptic contacts. The new pre-synaptic ribbons
      resemble those at the original sites except for being smaller. The sites are,
      moreover, monadic, with T1 now the sole post-synaptic partner. These results show
      that interneurons in the fly's lamina retain a dynamic capacity for
      synaptogenesis throughout much of adult life, normally a few weeks in Musca, and
      that during this synaptogenesis they re-enact the same cell preferences expressed
      earlier in development.

PMID- 1348116
TI  - The glutamate-receptor linked cGMP cascade of retinal on-bipolar cells is
      pertussis and cholera toxin-sensitive.
AB  - Whole-cell patch-clamp recordings were obtained from light-responsive on-bipolar
      cells in retinal slices of the dogfish. Inclusion of the A-subunit of pertussis
      toxin in the patch-pipette solution resulted in an increase in inward current and
      membrane conductance, and a block of light-evoked currents of on-bipolar cells.
      The opposite effect was obtained with the A-subunit of cholera toxin, which
      blocked light responses, and induced an outward current and a decrease in
      membrane conductance. These actions were NAD+ dependent. The results show that
      the G-protein(s) linking glutamate receptors to a cGMP cascade in on-bipolar
      cells possess sites which are ADP-ribosylated by pertussis and cholera toxins,
      with no homology to the adenylate cyclase system but possibly with a homology to
      transducin. Furthermore, inclusion of H-7, a kinase inhibitor in the patch
      pipette solution, or of a non-hydrolysable ATP analogue (AMP-PNP) had no effect
      on light responses, membrane conductance or dark current of on-bipolar cells,
      suggesting that the components of this cGMP cascade are unlikely to be regulated
      by protein kinases.

PMID- 1348117
TI  - Properties of the cGMP-activated channel of retinal on-bipolar cells.
AB  - Whole-cell patch-clamp recordings were obtained from on-bipolar cells in, or
      isolated from, retinal slices prepared from dogfish retina. The properties of the
      cGMP-activated conductance of on-bipolar cells were compared with that of rod
      photoreceptors. The on-bipolar cell cGMP-activated channel was blocked by L-cis
      diltiazem, a block which was strongly voltage dependent. However, this channel is
      not identical with that of photoreceptors. The location of the L-cis-diltiazem
      blocking site and its accessibility in the channel are not the same as in rods.
      The voltage dependence of block suggests that the blocking site, although near
      the intracellular side of the channel, is accessible to the positively charged
      form of L-cis-diltiazem only from the outward facing side of the channel.
      Furthermore, in contrast to rod channels, the conductance of the on-bipolar cell
      channels is unaltered by the removal of external divalent cations.

PMID- 1348118
TI  - Levels of inositol metabolites within normal myeloid blast cells and changes
      during their differentiation towards monocytes.
AB  - A homogeneous population of undifferentiated myeloid blast cells was purified
      from human fetal liver by rosette sedimentation of erythroblasts and macrophages,
      after coating these cells with monoclonal antibodies, followed by a cell
      elutriation step. The undifferentiated blast cells were maintained in culture, in
      a serum-free medium containing 1 mg l-1 inositol, by the presence of a high
      concentration of interleukin-3 (100 U ml-1). This allowed equilibrium labelling
      of cells with [2-3H]myo-inositol and analysis of the concentrations of inositol
      metabolites. The myeloid blast cells contained high concentrations of an
      unidentified inositol metabolite, possibly sn-glycero-3-phospho-1-inositol
      (GroPIns, 22 microM), inositol monophosphate (InsP, 16 microM), an unidentified
      inositol bisphosphate (InsP2, 9.4 microM), inositol pentakisphosphate (InsP5, 37
      microM) and inositol hexakisphosphate (InsP6, 31 microM). These high
      concentrations are similar to those reported in the promyeloid cell line, HL60.
      Treatment of the blast cells with 10 nM phorbol myristate acetate (PMA) resulted
      in rapid differentiation of 48% of the cells towards monocytes. Notable changes
      in the levels of inositol metabolites included an increase in the putative
      GroPIns peak (to 73 microM) and decreases in the concentrations of InsP4 (from 4
      microM to 1 microM) and InsP5 (to 21 microM). These changes in response to PMA,
      with the exception of the rise in the putative GroPIns, are similar to those
      reported in HL60 cells undergoing monocyte differentiation. These observations
      suggest that the abundant inositol polyphosphates may have an as yet unknown role
      in myeloid differentiation.

PMID- 1348119
TI  - Imaging voltage and synaptically activated sodium transients in cerebellar
      Purkinje cells.
AB  - Transient changes in sodium concentration in response to electrical activity were
      detected in Purkinje cells by using the fluorescent indicator SBFI (Minta & Tsien
      (J. biol. Chem. 264, 19,449 (1989)). Fast sodium action potentials caused large
      increases in internal sodium concentration, [Na]i, in the soma and axon, and were
      generally undetectable in the dendrites. No changes were detected in the
      dendrites corresponding to calcium action potentials. The spatial distribution of
      these transients corresponds to that expected if the increase in [Na]i were the
      result of Na+ entry through voltage-dependent Na channels generating sodium
      spikes in the axon hillock and soma. The [Na]i transients rapidly recovered (tau
      less than 1 s) in the axon hillock, probably by Na+ diffusion into the soma.
      Climbing fibre activation produced distinct [Na]i transients in the dendrites in
      addition to somatic and axonal signals. As regenerative potentials did not
      produce transients in this region, these signals may be caused by Na+ entry
      through ligand-gated channels. These results confirm and extend the description
      of channel distribution and electrical signalling in Purkinje cells.

PMID- 1348120
TI  - Identification and egg hatching activity of monohydroxy fatty acid eicosanoids in
      the barnacle Balanus balanoides.
AB  - Monohydroxy fatty acids (MHFAs) were isolated from homogenates of the barnacle
      Balanus balanoides and identified by gas chromatography-mass spectrometry (GC-MS)
      as 14- and 17-hydroxy docosahexaenoic acids, 8-, 11-, 12-, 15- and 18-hydroxy
      eicosapentaenoic acids, 13- and 16-hydroxyoctadecatrienoic acids and 9-, 13- and
      15-hydroxyoctadecadienoic acids. Each monohydroxy fatty acid was tested for egg
      hatching activity in a bioassay using Elminius modestus egg masses, but 8-hydroxy
      5, 9, 11, 14, 17-eicosapentaenoic acid (8-HEPE) was the only MHFA with barnacle
      egg hatching activity. Studies on the egg hatching activity of MHFAs prepared
      from the oxidation of polyunsaturated fatty acids showed that activity was
      confined to the 8-hydroxy isomer of eicosapentaenoic acid and arachidonic acid,
      and that unsaturation at C5 and C14, but not C17, was essential for activity. In
      addition, the 8(R) conformation is necessary for activity, as 8(R)-HEPE caused
      egg hatching at 10(-7) M whereas the enantiomer 8(S)-HEPE was inactive.

PMID- 1348121
TI  - Interactions between acidic matrix macromolecules and calcium phosphate ester
      crystals: relevance to carbonate apatite formation in biomineralization.
AB  - Control over crystal growth by acidic matrix macromolecules is an important
      process in the formation of many mineralized tissues. Earlier studies on the
      interactions between acidic macromolecules and carboxylate- and carbonate
      containing crystals showed that the proteins recognize a specific stereochemical
      motif on the interacting plane. Here we show that a similar stereochemical motif
      is recognized by acidic mollusc shell macromolecules interacting with four
      different organic calcium phosphate-containing crystals. In addition, an acidic
      protein from vertebrate tooth dentin was also observed to recognize a similar
      structural motif in one of the crystals. The characteristic motif recognized is
      composed of rows of calcium ions and phosphates arranged in a plane defined by
      two free oxygens and a phosphorus atom emerging perpendicular to the affected
      face. These observations may have a direct bearing on the manner in which control
      over crystal growth is exerted on carbonate apatite crystals commonly found in
      vertebrate tissues.

PMID- 1348122
TI  - Isolation of telomere junction fragments by anchored polymerase chain reaction.
AB  - We describe a simple polymerase chain reaction (PGR)-based method for isolating
      short stretches of nontelomeric DNA adjacent to arrays of telomere repeat units,
      in principle applicable to any species for which the telomere repeat sequence is
      known. Application of this approach to human DNA resulted in the isolation of
      many candidate telomere junction clones, at least some of which were shown to be
      derived from telomere-adjacent regions. Most of the isolated clones detect
      multiple sequences in the human genome which represent one or a few sequence
      families present at the ends of most or all autosomes and variably truncated
      before the start of the telomere repeat array. Substantial sequence divergence
      between different members of these sequence families suggests a low rate of
      sequence homogenization by telomere exchange processes. The pseudoautosomal
      telomere junction has also been isolated and contains a shortened version of a
      recently described family of short interspersed repetitive elements (SINEs), only
      14 base pairs (b.p.) from the start of the telomere.

PMID- 1348123
TI  - Extra-junctional ryanodine receptors in the terminal cisternae of mammalian
      skeletal muscle fibres.
AB  - The distribution of ryanodine receptor calcium-release channels over the terminal
      cisternae (TC) membrane of skeletal muscle fibres was examined by using
      immunogold electron microscopy. Two monoclonal antibodies (5C3 and 8E2) that
      bound to monomers of the ryanodine receptor protein on Western blots of SDS
      polyacrylamide gels were used to locate calcium-release channels in longitudinal
      sections of rat sternomastoid and diaphragm fibres. Up to 21% of 5C3 binding on
      TC membranes was extra-junctional, compared with 46% for 8E2. Binding of 8E2 to
      the fibres was less than half that of 5C3, possibly because of steric shielding
      of the 8E2 antigenic site at the junction. The distances between neighbouring
      particles in clusters was 20-40 nm, i.e. the distance between subunits of the
      ryanodine receptor or between neighbouring foot structures. We suggest that,
      during activation, extra-junctional ryanodine receptors may release Ca2+ directly
      into the myoplasm, rather than into the restricted space of the triad junction.

PMID- 1348124
TI  - Synergistic effect of Adh alleles in Drosophila melanogaster.
AB  - In laboratory cultures of Drosophila melanogaster derived from an African
      population, the quantities of six out of seven enzymes (G6PD, IDH, GPDH, ME, MDH,
      PGM and ADH) were higher in Adh-FF homozygotes than they were in Adh-SS. In
      crosses between Adh-FF and Adh-SS flies, the differences segregated as co
      dominant alleles of a single Mendelian gene closely linked, or identical, to the
      Adh locus. The generality of these associations was suggested by the study of a
      French population with a very different history and genetic background. The
      possibility that the associations were caused by artefacts of the immunodiffusion
      techniques, or to a linked inversion (In(2L)t), was excluded. Possible ways by
      which the Adh locus may affect the quantities of other enzymes are discussed.

PMID- 1348125
TI  - Beta-adrenoceptor subtypes in the detrusor of guinea-pig urinary bladder.
AB  - beta-Adrenoceptors have been demonstrated in the urinary bladders of many animals
      including the guinea pig. However, there is little information on the subtypes
      involved in the antispasmodic activity of beta-adrenoceptor activation in the
      guinea-pig detrusor. The present study uses the non-selective beta-agonist
      isoproterenol, the antagonist nadolol, the beta 2-selective agonists salbutamol
      and terbutaline, the antagonist ICI 118551, and the beta 1-selective antagonist
      metoprolol, to demonstrate functionally the subtypes existing in the guinea-pig
      detrusor. Isoproterenol dose-dependently reduces the myogenic activity in the
      guinea-pig detrusor induced by mild depolarization with 20 mM potassium in the
      tissue bath. At the supramaximal concentration of 30 microM, isoproterenol
      achieves 73 +/- 2% of the reference maximal response. This activity of
      isoproterenol is reduced to 9 +/- 5, 24 +/- 6 and 54 +/- 1% in the total blockade
      of beta, beta 1 and beta 2 with nadolol, metoprolol and ICI 118551, respectively.
      Consistently, salbutamol and terbutaline at the same concentration produce only
      35 +/- 1 and 38 +/- 4% of the response, respectively. Thus, both beta 1- and beta
      2-adrenoceptors are present in the detrusor of the guinea-pig urinary bladder.
      Although activation of either subtype results in antispasmodic action, the larger
      portion of the antispasmodic activity appears to be associated with the
      activation of the beta 1-subtype.

PMID- 1348126
TI  - Inhibition of vasopressin-sensitive cAMP accumulation by alpha 2-adrenoceptor
      agonists in collecting tubules is species dependent.
AB  - The ability of alpha 2-adrenoceptor agonists to inhibit vasopressin (VP)
      stimulated cAMP accumulation in collecting tubules and to inhibit the
      antidiuretic effect of VP in rats is clearly established. However, in other
      species, such as the dog, alpha 2-adrenoceptor-induced inhibition of VP action
      has not been convincingly demonstrated. In the present study, we examined the
      effects of epinephrine and other alpha 2-adrenoceptor agonists on VP-stimulated
      cAMP accumulation in inner medullary collecting tubule cells and/or cortical
      collecting tubules from a number of species. Epinephrine, oxymetazoline,
      clonidine, and guanabenz inhibited VP-induced cAMP formation in rat inner
      medullary collecting tubule cells with IC50s ranging from 10 to 30 nM. However,
      epinephrine or guanabenz had no effect on VP-stimulated cAMP formation in cells
      from dog, pig, rhesus monkey, or human inner medulla. Similarly, epinephrine
      inhibited VP-induced cAMP accumulation in cortical collecting tubules dissected
      from rat kidneys but not from dog or rabbit kidneys. We conclude that there is a
      marked species difference in the ability of alpha 2-adrenoceptor agonists to
      inhibit VP-induced cAMP formation at the tubular level. This may explain the
      difficulty in demonstrating an alpha 2-adrenoceptor agonist-induced inhibition of
      VP action in other species such as dog and man.

PMID- 1348127
TI  - Muscarinic regulation of somatostatin release from primary cultures of human
      antral epithelial cells.
AB  - A newly developed, primary culture of human antral epithelial cells has been
      utilized to examine the effect of parasympathomimetics on somatostatin release.
      The cholinergic agonists, carbachol and methacholine, stimulated somatostatin
      secretion in a concentration-dependent manner. Maximal release in response to
      carbachol was observed at 0.1 mmol/l. Methacholine was 10 times more potent with
      a significant release being observed at 1 mumol/l, maximal secretion was observed
      at 10 mumol/l. Somatostatin release, stimulated by the mixed nicotinic and
      muscarinic agonist, carbachol, was attenuated by the addition of atropine at 0.1
      mumol/l but was unaffected by the same concentration of pirenzepine. Methacholine
      stimulated release was attenuated by addition of 0.1 mumol/l atropine and
      unaffected by the same concentration of pirenzepine. The response to methacholine
      was reversed by the addition of 0.1 mumol/l 4-diphenylacetoxy-n-methylpiperidine
      methiodide (4-DAMP) and attenuated by 1 nmol/l 4-DAMP indicating that the effect
      was mediated by an M3 receptor. In conclusion, human antral D cells are
      stimulated by parasympathomimetics acting at an M3 receptor.

PMID- 1348128
TI  - Chronic nicotine intake increases the responses to muscarinic receptor
      stimulation.
AB  - Chronic nicotine administration depresses the autonomic ganglia, but its effects
      on the muscarinic receptors at the neuroeffector sites remain unclear. The
      present study, using rats, examines the influence of chronic treatment with
      nicotine (25 micrograms/ml drinking water) for 10 or 15 days on muscarinic
      receptor responses, as reflected by bethanechol-evoked gastric secretion or by
      acetylcholine-induced decreases in mean blood pressure. Bethanechol, 0.4, 0.8,
      1.6 or 3.2 mg/kg injected subcutaneously, dose-dependently increased the basal
      gastric secretory volume and acid output in pylorus-ligated control animals which
      normally drank tap water. Rats given nicotine in their drinking water for 10 or
      15 days showed a further marked increase in both the volume of gastric secretion
      and acid output in response to bethanechol injections. Although bethanechol dose
      dependently increased acid secretion, the ulcer index was very small and there
      was no significant difference between the control and nicotine-treated groups.
      The basal mean blood pressure remained normal after the 10-day nicotine
      treatment. Acetylcholine, 0.1, 0.3, 1 or 3 micrograms/kg given intravenously,
      decreased the mean blood pressure; this acetylcholine-evoked blood pressure fall
      was intensified by nicotine pretreatment. The findings suggest that the responses
      to muscarinic receptor stimulation are increased by chronic nicotine treatment
      for 10 or 15 days. These exaggerated effects are possibly the consequence of
      persistent autonomic ganglion blockade by chronic nicotine treatment.

PMID- 1348129
TI  - The development of face processing skills.
AB  - An early orientation to faces is followed by a gradual development of face
      processing skills. During the course of maturation, children acquire the ability
      to learn new faces and to deal with facial transformations. Some skills are
      achieved more quickly than others. Moreover, encoding ability in young children
      is somewhat different from that shown by older children. The younger groups fail
      to take advantage of increased inspection time and stimulus characteristics such
      as facial distinctiveness. They are also more likely to be confused by
      alterations in background context. Although with familiar faces they reveal very
      similar identity priming effects to older children and adults, younger children
      display a relative inefficiency in categorizing faces as being that of a target
      unless it is noticeably dissimilar. Young children are more likely than older
      people to prefer positive caricatures of certain faces, which is not consistent
      with the view that caricature effects are simple reflections of a general
      expertise with faces.

PMID- 1348131
TI  - Cognitive mechanisms of face processing.
AB  - Evidence from natural and induced errors of face recognition, from the effects of
      different cues on resolving errors, and from the latencies to make different
      decisions about seen faces, all suggest that familiar face recognition involves a
      fixed, invariant sequence of stages. To recognize a familiar face, a perceptual
      description of a seen face must first activate a long-standing representation of
      the appearance of the face of the familiar person. 'Semantic' knowledge about
      such things as the person's occupation and personality are accessed next,
      followed, in the final stage, by the name. Certain factors affect the ease of
      familiar face recognition. Faces seen in the recent past are recognized more
      readily (repetition priming), as are distinctive faces, and faces preceded by
      those of related individuals (associative priming). Our knowledge of these
      phenomena is reviewed for the light it can shed upon the mechanisms of face
      recognition. Four aspects of face recognition--graded similarity effects and part
      to-whole completion in repetition priming, prototype extraction with simultaneous
      retention of information about individual exemplars, and distinctiveness effects
      in classification and identification--are proposed as being compatible with
      distributed memory accounts of cognitive representations.

PMID- 1348130
TI  - Neurophysiological mechanisms underlying face processing within and beyond the
      temporal cortical visual areas.
AB  - The ways in which information about faces is represented and stored in the
      temporal lobe visual areas of primates, as shown by recordings from single
      neurons in macaques, are considered. Some neurons that respond primarily to faces
      are found in the cortex in the anterior part of the superior temporal sulcus (in
      which neurons are especially likely to be tuned to facial expression and to face
      movement involved in gesture), and in the TE areas more ventrally forming the
      inferior temporal gyrus (in which neurons are more likely to have responses
      related to the identity of faces). Quantitative studies of the responses of the
      neurons that respond differently to the faces of different individuals show that
      information about the identity of the individual is represented by the responses
      of a population of neurons, that is, ensemble encoding rather than 'grandmother
      cell' encoding is used. It is argued that this type of tuning is a delicate
      compromise between very fine tuning, which has the advantage of low interference
      in neuronal network operations but the disadvantage of losing the useful
      properties (such as generalization, completion and graceful degradation) of
      storage in neuronal networks, and broad tuning, which has the advantage of
      allowing these properties of neuronal networks to be realized but the
      disadvantage of leading to interference between the different memories stored in
      an associative network. There is evidence that the responses of some of these
      neurons are altered by experience so that new stimuli become incorporated in the
      network. It is shown that the representation that is built in temporal cortical
      areas shows considerable invariance for size, contrast, spatial frequency and
      translation. Thus the representation is in a form which is particularly useful
      for storage and as an output from the visual system. It is also shown that one of
      the representations that is built is object based, which is suitable for
      recognition and as an input to associative memory, and that another is viewer
      centred, which is appropriate for conveying information about gesture. Ways are
      considered in which such cortical representations might be built by competitive
      self-organization aided by back projections in the multi-stage cortical
      processing hierarchy which has convergence from stage to stage.

PMID- 1348132
TI  - Modelling face recognition.
AB  - Much early work in the psychology of face processing was hampered by a failure to
      think carefully about task demands. Recently our understanding of the processes
      involved in the recognition of familiar faces has been both encapsulated in, and
      guided by, functional models of the processes involved in processing and
      recognizing faces. The specification and predictive power of such theory has been
      increased with the development of an implemented model, based upon an
      'interactive activation and competition' architecture. However, a major
      deficiency in most accounts of face processing is their failure to spell out the
      perceptual primitives that form the basis of our representations for faces.
      Possible representational schemes are discussed, and the potential role of three
      dimensional representations of the face is emphasized.

PMID- 1348133
TI  - Organization and functions of cells responsive to faces in the temporal cortex.
AB  - Cells selectively responsive to the face have been found in several visual sub
      areas of temporal cortex in the macaque brain. These include the lateral and
      ventral surfaces of inferior temporal cortex and the upper bank, lower bank and
      fundus of the superior temporal sulcus (STS). Cells in the different regions may
      contribute in different ways to the processing of the facial image. Within the
      upper bank of the STS different populations of cells are selective for different
      views of the face and head. These cells occur in functionally discrete patches (3
      5 mm across) within the STS cortex. Studies of output connections from the STS
      also reveal a modular anatomical organization of repeating 3-5 mm patches
      connected to the parietal cortex, an area thought to be involved in spatial
      awareness and in the control of attention. The properties of some cells suggest a
      role in the discrimination of heads from other objects, and in the recognition of
      familiar individuals. The selectivity for view suggests that the neural
      operations underlying face or head recognition rely on parallel analyses of
      different characteristic views of the head, the outputs of these view-specific
      analyses being subsequently combined to support view-independent (object-centred)
      recognition. An alternative functional interpretation of the sensitivity to head
      view is that the cells enable an analysis of 'social attention', i.e. they signal
      where other individuals are directing their attention. A cell maximally
      responsive to the left profile thus provides a signal that the attention (of
      another individual) is directed to the observer's left. Such information is
      useful for analysing social interactions between other individuals.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1348134
TI  - Representation of visual stimuli in inferior temporal cortex.
AB  - In primates, inferior temporal (IT) cortex is crucial for the processing and
      storage of visual information about form and colour. This article reviews the
      properties of IT neurons and considers how these properties may underlie the
      perceptual and mnemonic functions of IT cortex. The available evidence suggests
      that the processing of the facial image by IT cortex is similar to its processing
      of other visual patterns. Faces and other complex visual stimuli appear to be
      represented by the pattern of responses over a population of IT neurons rather
      than by the responses of specific 'feature detectors' or 'grandmother' cells. IT
      neurons with adult-like stimulus properties are present in monkeys as young as
      six weeks old.

PMID- 1348136
TI  - The neuropsychology of lipreading.
AB  - Lipreading presents a unique glimpse of the intersection of sensory processes
      with modular, cognitive ones. It presents speech to the eye in an automatic and
      natural way, whether performed silently or in conjunction with heard speech. It
      therefore allows us to examine closely claims concerning the relation between
      input modality and cognitive function. In this paper I consider some of the ways
      in which the investigation of single neuropsychological cases casts light on
      this; such cases show us that lipreading can dissociate from other aspects of
      face perception and recognition, and from auditory speech perception and reading,
      too. Furthermore, different cognitive components of lipreading itself can be
      inferred from dissociations on different lipreading tasks. This leads to closer
      consideration of the boundaries of the necessary cognitive (and possibly
      anatomical) structures that subserve these functions.

PMID- 1348135
TI  - The role of the 'face-cell' area in the discrimination and recognition of faces
      by monkeys.
AB  - Cortical neurons that are selectively sensitive to faces, parts of faces and
      particular facial expressions are concentrated in the banks and floor of the
      superior temporal sulcus in macaque monkeys. Their existence has prompted
      suggestions that it is damage to such a region in the human brain that leads to
      prosopagnosia: the inability to recognize faces or to discriminate between faces.
      This was tested by removing the face-cell area in a group of monkeys. The animals
      learned to discriminate between pictures of faces or inanimate objects, to select
      the odd face from a group, to inspect a face then select the matching face from a
      pair of faces after a variable delay, to discriminate between novel and familiar
      faces, and to identify specific faces. Removing the face-cell area produced no or
      little impairment which in the latter case was not specific for faces. In
      contrast, several prosopagnosic patients were impaired at several of these tasks.
      The animals were less able than before to discern the angle of regard in pictures
      of faces, suggesting that this area of the brain may be concerned with the
      perception of facial expression and bearing, which are important social signals
      in primates.

PMID- 1348137
TI  - Face recognition impairments.
AB  - Face recognition impairments are often found in the context of brain injury
      involving the right cerebral hemisphere. Recognition impairments can be
      dissociated from impairments affecting the processing of other types of
      information carried by the face, such as expression. The face recognition
      impairments themselves take different forms, corresponding to idealized stages or
      levels of recognition. These types of error can also arise as transitory
      phenomena in normal everyday life. From these observations, psychologists have
      proposed functional models that characterize the organization of the face
      processing system in schematic form. Such models provide useful ways of
      summarizing what is known. More importantly, they also allow new findings to act
      as tests of each model's usefulness by the extent to which they can be readily
      accommodated or force revision. Examples of this are briefly considered,
      including delusional misidentification, impaired learning of new faces,
      disordered attention to faces, 'covert' recognition in prosopagnosia, and
      unawareness of impaired face recognition.

PMID- 1348138
TI  - Functional and anatomical decomposition of face processing: evidence from
      prosopagnosia and PET study of normal subjects.
AB  - Studies of brain-damaged patients have revealed the existence of a selective
      impairment of face processing, prosopagnosia, resulting from lesions at different
      loci in the occipital and temporal lobes. The lesions are often extensive, and it
      is unclear what functional aspects of face processing are normally served by the
      damaged areas, and whether they are uniquely devoted to the processing of faces.
      These issues are further addressed through a combined magnetic resonance imaging
      (MRI) and positron emission tomography (PET) study of regional cerebral blood
      flow (rCBF) in normal subjects performing different tasks of face and object
      processing. The results indicate different patterns of cerebral activation
      depending on the requirements of the tasks within the processing of faces, as
      well as a clear dissociation of the neural substrates underlying face and object
      processing. These results are compared with radiological data from prosopagnosic
      patients, and are put in relation with the patterns of deficits observed in the
      patients as a function of the location of their lesions. Together, the findings
      offer new evidence regarding the functional neuroanatomy of face and object
      processing.

PMID- 1348139
TI  - Facial expressions of emotion: an old controversy and new findings.
AB  - Evidence on universals in facial expression of emotion and renewed controversy
      about how to interpret that evidence is discussed. New findings on the capability
      of voluntary facial action to generate changes in both autonomic and central
      nervous system activity are presented, as well as a discussion of the possible
      mechanisms relevant to this phenomenon. Finally, new work on the nature of
      smiling is reviewed which shows that it is possible to distinguish the smile when
      enjoyment is occurring from other types of smiling. Implications for the
      differences between voluntary and involuntary expression are considered.

PMID- 1348140
TI  - Lipreading and audio-visual speech perception.
AB  - This paper reviews progress in understanding the psychology of lipreading and
      audio-visual speech perception. It considers four questions. What distinguishes
      better from poorer lipreaders? What are the effects of introducing a delay
      between the acoustical and optical speech signals? What have attempts to produce
      computer animations of talking faces contributed to our understanding of the
      visual cues that distinguish consonants and vowels? Finally, how should the
      process of audio-visual integration in speech perception be described; that is,
      how are the sights and sounds of talking faces represented at their conflux?

PMID- 1348141
TI  - The extraction and use of facial features in low bit-rate visual communication.
AB  - A review is given of experimental investigations by the author and his
      collaborators into methods of extracting binary features from images of the face
      and hands. The aim of the research has been to enable deaf people to communicate
      by sign language over the telephone network. Other applications include model
      based image coding and facial-recognition systems. The paper deals with the
      theoretical postulates underlying the successful experimental extraction of
      facial features. The basic philosophy has been to treat the face as an
      illuminated three-dimensional object and to identify features from
      characteristics of their Gaussian maps. It can be shown that in general a
      composite image operator linked to a directional-illumination estimator is
      required to accomplish this, although the latter can often be omitted in
      practice.

PMID- 1348142
TI  - The computer synthesis of expressive faces.
AB  - This paper presents a methodology for the computer synthesis of realistic faces
      capable of expressive articulations. A sophisticated three-dimensional model of
      the human face is developed that incorporates a physical model of facial tissue
      with an anatomical model of facial muscles. The tissue and muscle models are
      generic, in that their structures are independent of specific facial geometries.
      To synthesize specific faces, these models are automatically mapped onto
      geometrically accurate polygonal facial representations constructed by
      photogrammetry of stereo facial images or by non-uniform meshing of detailed
      facial topographies acquired by using range sensors. The methodology offers
      superior realism by utilizing physical modelling to emulate complex tissue
      deformations in response to coordinated facial muscle activity. To provide
      realistic muscle actions to the face model, a performance driven animation
      technique is developed which estimates the dynamic contractions of a performer's
      facial muscles from video imagery.

PMID- 1348143
TI  - Becoming a face expert.
AB  - Young children do not form representations of newly encountered faces as
      efficiently as do adults. A first step in explaining this difference, like any
      age-related change, is locating its source. A major source of the improvement is
      acquisition of knowledge of faces per se, as opposed to age-related changes in
      general pattern encoding or memorial skills. Two consequences of expertise at
      individualizing members of classes that share a basic configuration are known: a
      large inversion effect and a caricature advantage. It is possible that both of
      these effects reflect increased reliance, with expertise, on configuration
      distinguishing features. Several phenomena that indicate that inversion
      interferes with the encoding of configural aspects of faces are reviewed.
      Finally, developmental data are presented that confirm the suspicion that there
      are at least two distinct sources of the vulnerability of face encoding to
      inversion, perhaps reflecting two distinct senses of 'configural encoding' of
      faces, only one of which is implicated in adult expertise at face encoding.

PMID- 1348144
TI  - Racial differences in the relaxation response of hypertensives.
AB  - Racial differences in the relaxation response of hypertensives maintained on
      diuretic were investigated by comparing blood pressure, muscle tension, and hand
      temperature changes occurring with biofeedback assisted relaxation. Resting blood
      pressures were not different in blacks compared with whites. Both black and white
      subjects decreased diastolic blood pressure significantly from baseline values,
      but only whites significantly decreased systolic blood pressure. Though both
      blacks and whites significantly decreased forehead muscle tension, black subjects
      showed no changes in finger temperature while whites increased temperature
      significantly. The lack of change in finger temperature in blacks may be a
      reflection of the increased peripheral resistance previously associated with the
      greater incidence of hypertension in the American black population.

PMID- 1348145
TI  - Contribution of amino acid transmitters to epileptiform activity and reflex
      suppression in electrically head stunned sheep.
AB  - In sheep, administration of a combination of zolazepam and tiletamine
      hydrochloride resulted in a dose dependent reduction in the duration of epileptic
      activity induced by an electric stun applied to the head. The compound also
      lengthened the normal period of reflex suppression that occurs after a stun.
      Excitatory amino acid receptor antagonists (2-amino-7-phosphonoheptanoic and 2
      amino-5-phosphonovaleric acids) also reduced the duration of epileptic activity
      following an electric stun. These drugs did not alter the time of pedal and ear
      pinch reflex suppression. Administration of bicuculline (a gamma amino-4-butyric
      acid [GABA] receptor antagonist) reduced the period of stun induced reflex
      suppression and increased seizure duration. Administration of a GABA receptor
      agonist, baclofen, increased the duration of reflex suppression. The results
      suggest that the development of epileptiform-like activity following application
      of an electric current to the head is dependent upon excitatory amino acid
      receptors. The reflex suppression that also arises following an electric stun is
      contributed to by the activation of GABA receptor mechanisms.

PMID- 1348146
TI  - Mediation of contraction and relaxation by alpha- and beta-adrenoceptors in the
      ureterovesical junction of the sheep.
AB  - The effects of alpha- and beta-adrenoceptor agonists and antagonists were studied
      in the sheep ureterovesical junction. Non-specific adrenergic agonists such as
      adrenaline and noradrenaline induced contraction in the sheep ureterovesical
      junction, suggesting a predominance of alpha-over beta-adrenoceptors in this
      functional unity. An inhibition of the noradrenaline-induced contraction was
      observed after prior blocking with prazosin (10(-7) M) and yohimbine (10(-7) M),
      the effect of prazosin being more potent than that of yohimbine. The effect of
      phenylephrine on alpha 1-adrenoceptors was more potent than that of B-HT 920 on
      alpha 2-adrenoceptors. Isoproterenol caused a concentration-dependent relaxation
      that was inhibited by propranolol (10(-6) M), pafenolol (10(-5) M) and butoxamine
      (10(-5) M). These results suggest that ureterovesical junction contraction is
      mediated by both alpha 1 and alpha 2-adrenoceptors, alpha 1 predominating over
      alpha 2. Relaxation is mediated by beta-adrenoceptors of the beta 1 and beta 2
      subtypes.

PMID- 1348147
TI  - Effects of prostaglandin E2 on ganglionic transmission in the guinea pig trachea.
AB  - We studied the effects of prostaglandin E2 (PGE2) on the contractile responses of
      in vitro guinea pig tracheal preparations with intact vagal innervation. The
      preparation was stimulated either through the vagal nerves (NS) or with an
      electrical field (EFS) and trachealis response was assessed from the pressure
      change inside the tracheal tube. Ganglionic blockade by hexamethonium inhibited
      responses to NS but did not affect EFS while both responses to NS and EFS were
      abolished by atropine or tetrodotoxin. This indicates that responses to both
      stimulation modalities were mediated by cholinergic nerves but that NS involved a
      ganglionic relay whereas EFS did not. Within the frequency range of 0.1-20 Hz,
      there was a gradual increase in the pressure generated by the trachealis muscle
      with increasing frequency of stimulation. The frequency-response relationship was
      similar for NS and EFS. Thus, the ganglion does not appear to play an important
      filtering or amplifying role under those conditions. PGE2 (1-50 mM) produced a
      concentration-dependent inhibition of NS and EFS without affecting responses to
      exogenous acetylcholine (ACh). This suggests that the main action of PGE2 is to
      reduce ACh release from post-ganglionic nerve terminals. PGE2 inhibited EFS to a
      larger extent than NS; we postulate a possible excitatory effect of PGE2 on
      neurotransmission in the airway ganglia.

PMID- 1348148
TI  - Evidence of a role for heterotrimeric GTP-binding proteins in endosome fusion.
AB  - Guanosine triphosphate (GTP)-binding proteins are required for intracellular
      vesicular transport. Mastoparan is a peptide component of wasp venom that
      increases nucleotide exchange in some classes of G alpha subunits of regulatory
      heterotrimeric GTP-binding proteins (G proteins). Mastoparan and other compounds
      that increase nucleotide exchange by G proteins inhibited endosome fusion in
      vitro and reversed the effects of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma
      S), a nonhydrolyzable GTP analog. Addition of beta gamma subunits of G proteins
      to the fusion assay antagonized the stimulatory effect of GTP-gamma-S, confirming
      the participation of G proteins. These results indicate that GTP-binding proteins
      are required for endosome fusion and in particular that a G protein is involved.
      Given the function of G proteins in signal transduction, these findings may
      provide insight into the mechanism by which endosomal vesicles become competent
      for fusion after their formation at the cell surface.

PMID- 1348149
TI  - [Fracture lines of the foot].
AB  - In follow-up examinations of 112 patients who had been diagnosed as having a
      sprained foot, bony lesions, confirmed by X-ray films, were found in 96 (85.7%)
      patients. Up to this time the fractures had not been found in 58 of them. The
      fractures were found to be distributed in a point-specific location, i.e., a
      precisely defined anatomical area in 43 cases (44.8%) and a linear presentation
      in 53 (55.2%). This linear grouping of bony injuries is seen to develop along the
      path of joints, bones and ligamental insertions that anatomically follow one
      another in a functional manner. The line-like pattern to these presentation
      permitted us to develop 3 line sets that could be attributed to specific
      mechanisms of injury. The lateral line (56.6%) specially follows a supination
      sprain to the foot. The medial line (20.8%) is seen to follow injuries that
      involved a blow along the longitudinal axis. The transverse line (22.6%) follows
      trauma involving the Chopart joint. Six diagrams are presented to illustrate the
      mechanisms of foot trauma, with their vectors of force and the corresponding
      injuries that may result. Radiological examples of several clinical cases are
      given to demonstrate these three fracture lines.

PMID- 1348150
TI  - Cytokines as modulators of cytotoxic drugs in experimental and clinical
      hematology and oncology. International Symposium. January 17-19, 1991.

PMID- 1348151
TI  - Protection of pancreatic and biliary anastomosis after partial
      duodenopancreatectomy by external drainage.
AB  - The pancreaticojejunostomy after duodenopancreatectomy is the "Achilles' heel" of
      the procedure. Herein we describe a technique for percutaneous drainage of the
      efferent limb of the Roux-en-Y loop relieving tension from the anastomosis.
      Seventy-six Whipple procedures, using this technique, have been done. The
      operative mortality rate was 1.3 per cent and anastomosis leakage occurred in two
      instances. In addition, one patient had to be reoperated upon for biliary
      fistula. Our technique for external Roux-en-Y loop drainage after partial
      duodenopancreatectomy is safe and efficient and permits rapid diagnosis of
      anastomotic complications.

PMID- 1348152
TI  - [Primary decontamination: vomiting, gastric irrigation or only medicinal
      charcoal?].
AB  - Procedures to reduce the absorption of ingested poisons have been employed widely
      for decades in the management of intoxicated patients. However, evidence of
      substantial clinical benefit to the majority of patients undergoing such
      treatments is lacking. Volunteer studies suggest that activated charcoal is
      generally more effective than either syrup of ipecacuanha or gastric lavage,
      though lavage may be more effective than syrup of ipecacuanha. Studies in
      poisoned patients have shown that although lavage is more effective than syrup of
      ipecacuanha, it led to a better outcome in comatose patients only if performed
      less than one hour after overdose. Syrup of ipecacuanha did not alter the outcome
      beneficially in those who were alert on presentation and is known to produce
      significantly more complications than charcoal alone even in patients who are
      awake with a gag reflex. A recent study suggests that activated charcoal may be
      superior both to lavage and syrup of ipecacuanha. Based on these studies it would
      seem reasonable to recommend that 50 to 100 g activated charcoal be administered
      to patients who have taken a substantial amount of a toxic substance less than
      one hour previously. This may be done conveniently by using an orogastric tube,
      which would also allow lavage to be undertaken with possible additional benefit.

PMID- 1348153
TI  - [Doubt about atenolol in the treatment of hypertension. Beta blockers, diuretics
      and the aged].

PMID- 1348154
TI  - [Doubt about atenolol in the treatment of hypertension. Beta blockers, diuretics
      and the aged].

PMID- 1348155
TI  - An immunohistological demonstration of c-erbB-2 oncoprotein expression in primary
      urothelial bladder cancer.
AB  - Sections of formalin-fixed, paraffin-blocked tissue from 116 primary transitional
      cell carcinomas were stained immunohistochemically using a polyclonal antibody
      against the c-erbB-2 oncoprotein. Positive staining of cell membranes, known to
      correlate with gene amplification, was seen in 22 (19%) of the 116, with variable
      staining from tumour to tumour and within tumours themselves. Consistent with its
      mooted value as a prognosticator in bladder cancer, the c-erbB-2 oncoprotein was
      detected in 13 (of 40) grade III and 9 of the 26 muscle-invasive tumours examined
      compared to 1 (of 25) grade I and 6 (of 66) mucosa only (pTa) lesions. These
      results support further examination of c-erbB-2 expression in bladder cancer.

PMID- 1348157
TI  - [Localization of somatostatin mRNA in the rat retina detected by in situ
      hybridization histochemistry].
AB  - In order to determine the localization of the mRNA encoding somatostatin in the
      rat retina, we studied Sprague-Dawley rats by in situ hybridization
      histochemistry. Radiolabelled oligodeoxyribonucleotides complementary for rat
      somatostatin mRNA were used in this study. Among the layers of the retina, we
      found specific labelling in the soma of some cells in the innermost and outermost
      laminae of the inner-nuclear layer and in the ganglion cell layer. These results
      indicate the major site of somatostatin synthesis within the rat retina.

PMID- 1348156
TI  - Factor-XIIIa-expressing dermal dendrocytes in Kaposi's sarcoma. A comparison
      between classical and immunosuppression-associated types.
AB  - The histogenetic origin of Kaposi's sarcoma is a matter of controversy, with
      recent reports claiming it to derive from the factor-XIIIa-positive dermal
      dendrocyte rather than endothelial cells. We investigated the potential role of
      factor-XIIIa-positive dermal dendrocytes in the genesis of both classical
      (endemic) and immunosuppression-associated Kaposi's sarcoma. Thirteen cases of
      classical and 16 cases of immunosuppression (mostly AIDS)-associated Kaposi's
      sarcoma were immunostained with antibodies to factor XIIIa and to the blood-group
      antigen H, recognizing endothelial cells. Factor-XIIIa-positive cells were
      consistently antigen-H-negative and represented only a small percentage (usually
      less than 10%) of the proliferative cells. Their relative density tended to be
      decreased in immunosuppression-associated Kaposi's sarcoma when compared with
      that of the classical form. These results do not support the view that dermal
      dendrocytes may be the cells of origin of Kaposi's sarcoma; conversely, their
      decreased density in cases of immunosuppression-associated Kaposi's sarcoma could
      be related to immunosuppression and may account for more rapid tumour growth.

PMID- 1348158
TI  - Cardiovascular thrombosis and cardiac arrhythmia: current and future management.
      Proceedings of a symposium. Las Vegas, Nevada, July 1990.

PMID- 1348159
TI  - Relapse-preventing effect and safety of sulfasalazine and olsalazine in patients
      with ulcerative colitis in remission: a prospective, double-blind, randomized
      multicenter study. The Ulcerative Colitis Multicenter Study Group.
AB  - Forty-nine patients with ulcerative colitis in remission were entered into a
      prospective, double-blind, multicenter trial comparing the relapse-preventing
      effect and safety of 4 g sulfasalazine and 2 g olsalazine daily during 48 wk. Of
      the 46 evaluable patients, 23 were assigned to sulfasalazine and 23 to
      olsalazine. Seven of 23 patients (30.4%) relapsed on sulfasalazine and six of 23
      patients (26.1%) on olsalazine (95% confidence interval of the difference -22.0%
      to 30.3%). The relapse-free survival curves did not differ significantly at any
      time during the trial period. In both treatment groups, three patients dropped
      out because of adverse effects. Four patients on sulfasalazine and six patients
      on olsalazine experienced minor adverse effects. One patient on sulfasalazine had
      mild leukopenia, and four patients on sulfasalazine and one patient on olsalazine
      had decreased levels of haptoglobin. Thus, sulfasalazine and olsalazine are
      equally effective in maintaining remission of ulcerative colitis and are
      accompanied by a similar incidence of adverse effects.

PMID- 1348160
TI  - Familial association of autoimmune thrombocytopenia and hyperthyroidism.
AB  - An association between thrombocytopenia and thyrotoxicosis in a single individual
      is well documented, and the theories for this event include a common immunologic
      cause or a thyrotoxic-induced decrease in platelet survival. We report the first
      description of the coexistence of autoimmune thrombocytopenic purpura (AITP) and
      Graves' disease in several members of the same family, in which four females were
      thrombocytopenic and two of these were also hyperthyroid. All four patients had
      high titers of antiplatelet antibodies, and the two hyperthyroid cases were
      positive for thyroid-stimulating immunoglobulins (TSI). The familial occurrence
      of two autoimmune disorders is very uncommon, and suggests a genetic etiology.
      The HLA phenotype was determined and the antigens B8 and DR3, which are reported
      with high frequency in both diseases, were present in three patients. Although
      the etiologic cause is still unknown, our findings further support the theory
      that a genetic predisposition underlies autoimmune disease.

PMID- 1348161
TI  - Alprazolam as a neuroleptic adjunct in the emergency treatment of schizophrenia.
AB  - OBJECTIVE: While neuroleptics remain the mainstay of drug intervention in the
      emergency management of psychosis, a variety of agents have received study as
      alternatives or adjuncts to these drugs in an attempt to improve the safety and
      efficacy of acute treatment. The purposes of this study were to investigate the
      efficacy and safety of alprazolam as a neuroleptic adjunct for schizophrenic
      patients in psychotic relapse and to clarify the effects of combination treatment
      on specific aspects of the psychotic process. METHOD: Twenty-eight acutely
      psychotic patients with schizophrenia who were admitted to an emergency
      psychiatric service were randomly assigned to treatment with either haloperidol
      and alprazolam or haloperidol with placebo under double-blind conditions. Drug
      administration lasted 72 hours. RESULTS: Both groups improved significantly. The
      combination-treated group required significantly less medication and had 56%
      fewer dystonic reactions. The addition of alprazolam was most effective for
      symptoms of excitement and uncooperativeness, particularly in the initial hours
      of treatment. CONCLUSIONS: The combination of alprazolam and haloperidol seems to
      be the most effective for agitated patients, particularly in the first 48 hours
      of treatment. It may also result in fewer dystonic reactions.

PMID- 1348162
TI  - Prospective study of neuroleptic-induced dystonia in mania and schizophrenia.
AB  - OBJECTIVE: The authors' goal was to conduct a prospective study comparing the
      rate of occurrence of neuroleptic-induced dystonia in a group of consecutively
      admitted manic and schizophrenic patients receiving typical inpatient treatment
      from several clinicians. METHOD: All patients met the following criteria: 1) male
      sex, 2) age between 17 and 45 years, 3) definite diagnosis of mania or
      schizophrenia according to Research Diagnostic Criteria, 4) no exposure to
      neuroleptics during the past month, 5) absence of past or family history of a
      neurodegenerative disorder with extrapyramidal symptoms. All treatment decisions
      were left to the treating clinicians. Fifty patients with mania and 33 with
      schizophrenia were included in the study. Most of these patients received high
      potency neuroleptics, but the specific neuroleptic used varied in the two groups.
      RESULTS: Twelve (24%) of the patients with mania and five (15%) of the patients
      with schizophrenia developed acute dystonia. Manic patients received
      significantly higher peak doses of neuroleptics during the risk period for
      dystonia. Stepwise multiple regression analysis revealed that the peak
      neuroleptic dose and age were most strongly related to the occurrence of
      dystonia. CONCLUSIONS: This prospective study failed to support the retrospective
      finding of another study that acute dystonia occurred more often in manic
      patients than in patients with nonparanoid schizophrenia. The authors conclude
      that there is a need for carefully controlled prospective studies with larger
      groups of patients.

PMID- 1348163
TI  - Comorbidity in mania at first hospitalization.
AB  - Comorbidity was studied in 41 manic and mixed-state bipolar patients at first
      hospitalization. The lifetime prevalence of comorbidity was high; 21 subjects
      (51.2%) had at least one other psychiatric diagnosis (N = 16, 39.0%) or medical
      disorder (N = 9, 22.0%). Nine subjects had multiple comorbid diagnoses. Women
      were 2.7 times more likely to have a comorbid diagnosis. The presence of
      comorbidity was not associated with differences in outcome measures.

PMID- 1348165
TI  - American Association of Anatomists 105th Annual Meeting. March 11-14, 1992, New
      York, New York. Abstracts.

PMID- 1348164
TI  - GABA-benzodiazepine receptors.

PMID- 1348166
TI  - Pharmacokinetics and pharmacodynamics of vecuronium in the obese surgical
      patient.
AB  - The effect of obesity on the disposition and action of vecuronium was studied in
      14 surgical patients. After induction of anesthesia with thiopental and
      maintenance of anesthesia by inhalation of nitrous oxide and halothane, seven
      obese patients (93.4 +/- 13.9 kg, 166% +/- 30% of ideal body weight, mean +/- SD)
      and seven control patients (60.9 +/- 12.3 kg, 93% +/- 6% of ideal body weight)
      received 0.1 mg/kg of vecuronium. Plasma arterial concentrations of muscle
      relaxant were determined at 1, 3, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180,
      210, 240, 300, and 360 min by a spectrofluorometric method. Simultaneously,
      neuromuscular blockade was assessed by stimulation of the ulnar nerve and
      quantification of thumb adductor response. Times to 50% recovery of twitch were
      longer in the obese than in the control patients (75 +/- 8 versus 46 +/- 8 min)
      as were 5%-25% recovery times (14.9 +/- 4.0 versus 10.0 +/- 1.7 min) and 25%-75%
      recovery times (38.4 +/- 13.8 versus 16.7 +/- 10.3 min). However, vecuronium
      pharmacokinetics were similar for both groups. When the data were calculated on
      the basis of ideal body weight (IBW) for obese and control patients, total volume
      of distribution (791 +/- 303 versus 919 +/- 360 mL/kg IBW), plasma clearance
      (4.65 +/- 0.89 versus 5.02 +/- 1.13 mL.min-1.kg IBW-1), and elimination half-life
      (119 +/- 43 versus 133 +/- 57 min) were not different between groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1348167
TI  - Atracurium and vecuronium: repeated bolus injection versus infusion.
AB  - The purpose of this study was to compare the characteristics of recovery from
      neuromuscular blockade after either atracurium or vecuronium given by intravenous
      infusion or by repeated injection. Four groups of 10 patients each were studied
      during nitrous oxide narcotic anesthesia. An initial intravenous dose of 2 x ED95
      of either muscle relaxant was followed by an intravenous infusion started at 5%
      recovery of control twitch tension and adjusted for 95% block or by repeated
      injection of 0.6 x ED95 administered whenever twitch tension had returned to 25%
      of control. There were no significant differences between the maintenance doses
      required based on method of administration: atracurium repeated injection, 1.6 +/
      0.3 x ED95 h-1; atracurium infusion, 1.7 +/- 0.3 x ED95 h-1; vecuronium repeated
      injection, 1.8 +/- 0.5 x ED95 h-1; and vecuronium infusion, 1.6 +/- 0.4 x ED95 h
      1. Nevertheless, differences of up to 20 min were noted in the recovery indices
      in the following order: atracurium repeated injection = atracurium infusion less
      than vecuronium repeated injection less than vecuronium infusion. A single dose
      of neostigmine (7 micrograms/kg) significantly reduced the recovery indices,
      thereby eliminating their differences.

PMID- 1348168
TI  - Subjective, behavioral, and physiologic responses to intravenous dezocine in
      healthy volunteers.
AB  - Dezocine is an agonist-antagonist opiate that acts at the mu receptor, and is
      used for management of pain. Monkeys will readily press a lever to receive an
      injection of dezocine, and in former opiate addicts dezocine produces positive
      subjective effects similar to those of morphine. It is not clear, however, what
      its subjective effects are in people who do not have a history of opiate abuse.
      To answer this question, a within-subjects design was used in which 10 normal
      healthy volunteers (six men, four women) were injected with 0, 2.5, 5.0, and 10
      mg/70 kg of dezocine in a double-blind fashion. Subjects completed several
      questionnaires (e.g., Addiction Research Center Inventory) commonly used in abuse
      liability testing before and at periodic intervals for up to 5 h after drug
      injection. We also assessed psychomotor performance (e.g., eye-hand coordination)
      and several physiologic measures (e.g., pupil size, respiration rate) at these
      times. Dezocine produced increases in ratings of drug liking (P less than 0.001),
      as well as other subjective effects that might be considered as pleasant ("good
      mood," "drunken," "coasting," "happy" ratings) (all P less than 0.05). At the
      same time, the drug had effects (increased dysphoria and sedation) that typically
      are not reported by addicts. Dezocine produced psychomotor impairment and miosis
      (constriction of the pupils) in a dose-dependent fashion. The observation that
      dezocine produces euphoria and increased drug-liking ratings in individuals
      without histories of drug abuse suggests that hospitals and surgicenters should
      have strict accountability procedures with this drug.

PMID- 1348169
TI  - Characteristics of the inflammation in biopsies from large airways of subjects
      with asthma and subjects with chronic airflow limitation.
AB  - Although the characteristics of the histopathologic changes present in subjects
      who die with status asthmaticus are well documented, the structural changes
      present in subjects with mild to moderately severe asthma are not well described
      and the inflammatory changes in the large airways of subjects with chronic
      airflow limitation (CAL) and asthma have not been compared. Ten subjects with
      asthma, five taking inhaled corticosteroids and five taking beta 2-agonist
      aerosols, five subjects with CAL, and four subjects with no respiratory illness
      had four biopsies taken from airways 10 mm in diameter. The length of intact
      epithelium, thickness of basement membrane, and number of lymphocytes,
      neutrophils, eosinophils, plasma cells, monocytes, and mast cells in the lamina
      propria, bronchial smooth muscle, and submucosa were measured. Intact epithelium
      was present along 56% of the basement membrane in the asthmatic subjects, along
      54% in the subjects with CAL, and along 84% in the control subjects. In the
      asthmatic subjects there was no direct relationship between the severity of
      asthma and the amount of epithelial cell loss or the number of inflammatory
      cells. The basement membrane was thickened in all asthmatic subjects but not in
      normal subjects or subjects with CAL. There was a significant increase in the
      number of lymphocytes, eosinophils, and mast cells in the asthmatic airways,
      particularly in the lamina propria, compared with the CAL subjects. There were no
      eosinophils or mast cells in any of the control subjects. The airways of subjects
      with CAL contained significantly more inflammatory cells than the control
      subjects. Subjects with asthma on inhaled corticosteroids had significantly fewer
      lymphocytes, eosinophils, and mast cells compared with subjects taking only beta
      2-agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348170
TI  - Transaortic patch angioplasty for left coronary ostial stenosis in a patient with
      Takayasu's aortitis.
AB  - A 35-year-old woman who had left coronary ostial stenosis and aortic valve
      regurgitation due to Takayasu's aortitis underwent transaortic patch enlargement
      of the stenosed left coronary ostium in combination with aortic valve
      replacement. This technique may be suitable and recommendable as an alternative
      to aortocoronary bypass grafting or endarterectomy for coronary ostial stenosis
      in Takayasu's aortitis.

PMID- 1348171
TI  - 1990: Results of internal thoracic artery grafting over 15 years: single versus
      double grafts. 1992 update.

PMID- 1348172
TI  - Comparison of the effects of insulin and adrenergic agonists on the
      phosphorylation of an acid-soluble 22 kDa protein in rat epididymal fat-pads and
      isolated fat-cells.
AB  - 1. Earlier studies have shown that exposure of fat-cells to insulin results in
      the rapid increased phosphorylation of an acid-soluble 22 kDa protein and that
      increases in phosphorylation were also evident in cells exposed to adrenaline
      [Belsham & Denton (1980) Biochem. Soc. Trans. 8, 382-383; Belsham, Brownsey,
      Hughes & Denton (1980) Diabetologia 18, 307-312]. 2. The effects of adrenaline
      are shown to be brought about through beta-adrenergic receptors and to be
      mimicked by other agents which increase cell cyclic AMP concentrations. The
      maximum extent of phosphorylation is about 60% of that observed with insulin.
      Increased phosphorylation is also observed in fat-cells exposed to vasopressin,
      oxytocin and phorbol esters, but not to alpha-adrenergic agonists. 3. No changes
      in the phosphorylation of the protein are evident in epididymal fat-pads from fat
      fed, starved or starved/refed animals, despite the large changes in protein
      composition of fat-cells which accompany these nutritional alterations. This
      suggests that the protein is not closely involved in lipogenesis or associated
      metabolic pathways, but rather that it may play a more general regulatory role.
      4. The 22 kDa protein migrates as a doublet on SDS/PAGE even after purification
      to apparent homogeneity by sequential use of Mono Q chromatography, SDS/PAGE and
      h.p.l.c. The amino acid compositions of the two components are very similar and
      share features in common with a number of proteins, including inhibitor-1,
      inhibitor-2, dopamine- and cyclic-AMP-regulated phosphoprotein (DARPP-32), and G
      substrate, which may be involved in the regulation of protein phosphatase
      activity. 5. Phosphopeptide mapping and phosphoamino acid analysis reveals that
      insulin increases the phosphorylation of two distinct peptides within the protein
      (in one peptide insulin increases the amount of phosphothreonine, whereas in the
      other the hormone increases the amounts of phosphothreonine and phosphoserine).
      Both components of the doublet exhibit similar changes in phosphorylation, and
      hence the differences in migration are not the result of differences in
      phosphorylation, as suggested previously [Blackshear, Nemenoff & Avruch (1983)
      Biochem. J. 214, 11-19]. The pattern of phosphorylation observed with the beta
      adrenergic agonist isoprenaline was similar to that observed with insulin. 6. The
      possible role and regulation of the 22 kDa protein are discussed.

PMID- 1348174
TI  - Factors that govern the specificity of transglutaminase-catalysed modification of
      proteins and peptides.

PMID- 1348173
TI  - Stabilization of the oxy form of tyrosinase by a single conservative amino acid
      substitution.
AB  - Asp-208 of Streptomyces glaucescens tyrosinase (an invariant residue in the CuB
      binding region of tyrosinases and haemocyanins) was conservatively substituted by
      glutamic acid. Although having little effect on spectroscopic or kinetic
      properties of the enzyme, the mutation greatly decreased the lability of Cu-bound
      O2. A rationalization for these results is given, based on the crystal structure
      of Panuliris interruptus haemocyanin in the conserved CuB-binding region.

PMID- 1348175
TI  - Drug resistance dependent on different molecular size P-glycoproteins in Yoshida
      rat ascites hepatoma cells.

PMID- 1348176
TI  - Innervation of the endolymphatic sac.
AB  - Previous studies suggest that the endolymphatic sac plays an important role in
      the homeostasis of endolymph. Factors that influence blood flow in the sac may
      affect its function. This blood flow may be influenced by autonomic innervation;
      however, no such innervation has been demonstrated. The purpose of this study was
      to demonstrate catecholaminergic and cholinergic fibers on the endolymphatic sac.
      Endolymphatic sacs from Hartley guinea pigs were stained either
      immunocytochemically for tyrosine hydroxylase to reveal catecholaminergic fibers
      or histochemically for acetylcholinesterase to reveal cholinergic fibers. For
      tyrosine hydroxylase immunostaining, the endolymphatic sacs were treated with
      dilute hydrogen peroxide and then incubated in the primary antiserum. The tissue
      was further processed by the avidin-biotin immunoperoxidase method and reacted
      with diaminobenzidine. For acetylcholinesterase histochemistry, the tissue was
      processed by a modification of the direct thiocholine method. Light microscopy of
      the whole-mounted endolymphatic sacs revealed tyrosine hydroxylase-positive and
      acetylcholinesterase-positive fibers. Some of the acetylcholinesterase-positive
      fibers were clearly associated with vessels. This innervation, which has not been
      described previously, may significantly influence blood flow and function of the
      endolymphatic sac.

PMID- 1348178
TI  - Thyrotrophin-blocking antibodies in congenital hypothyroidism.
AB  - The role of transplacental transfer of maternal thyrotrophin (TSH)-blocking
      antibodies causing congenital hypothyroidism in Southern Chinese children was
      examined in this study. Twenty-two mothers of 24 patients with congenital
      hypothyroidism were studied 3-5 years after delivery. None of them had thyroid
      dysfunction at delivery or at the time of study. None had antithyroglobulin or
      antimicrosomal antibody. Only one mother was found to have TSH-binding inhibitory
      immunoglobulin (TBII), and her child had agenesis of the thyroid. This women had
      Graves disease in remission for 2 years before delivery. None had TSH-stimulated
      cAMP response inhibitory immunoglobulin (TSII). Ten of the 24 congenital
      hypothyroid children had transient neonatal hypothyroidism, seven had agenesis of
      the thyroid, six had dyshormonogenesis and one had a sublingual thyroid. As none
      of the mothers who had children with transient neonatal hypothyroidism had
      blocking antibodies at the time of study, the aetiology of the transient neonatal
      hypothyroidism remains unclear. These data suggest that maternal TSH-blocking
      antibodies do not play a role in most cases of sporadic congenital
      hypothyroidism.

PMID- 1348177
TI  - Enzymuria in neonates receiving continuous intravenous infusion of gentamicin.
AB  - Urinary excretion of the tubular enzymes NAG and AAP was investigated during
      gentamicin treatment of 105 newborn infants. The values found for NAG and AAP
      show a significant positive correlation. The urinary excretion of NAG was on the
      average 92% higher during gentamicin treatment as compared with non-treatment
      periods in the same newborn infant (33 infants). The same tendency applied to
      AAP. Newborn infants receiving continuous intravenous infusion of gentamicin were
      not found to be at greater risk of nephrotoxicity than those receiving
      intermittent gentamicin treatment, using NAG and AAP as an index of
      nephrotoxicity. The changes in NAg and AAP within treatment periods were studied.
      During gentamicin treatment an insignificant average increase in the urinary
      excretion of NAG occurred, whereas a significant decrease was found during non
      treatment periods. A significant negative correlation was found between urinary
      excretion of NAG and birth weight/gestational age. The long-term effect of the
      higher excretion of NAG and AAP in newborn and adult patients during
      aminoglycoside treatment is unknown.

PMID- 1348179
TI  - A bit of a handful ...

PMID- 1348180
TI  - The Third International Congress on Laser Technology in Ophthalmology. May 22-25,
      1991, San Francisco, Calif.

PMID- 1348181
TI  - Sympathetic nerve anatomy in the cavernous sinus and retrobulbar orbit of the
      cynomolgus monkey.
AB  - We present new information regarding the sympathetic nerve anatomy in the
      cavernous sinus and retrobulbar orbit of the cynomolgus monkey. Postganglionic
      sympathetic nerves were identified using an immunoperoxidase technique in which
      the primary antiserum was directed against tyrosine hydroxylase, the rate
      limiting enzyme in norepinephrine synthesis. Our work is unique in adapting this
      staining method to paraffin-embedded tissue. This technique allows sympathetic
      nerve fibers to be distinguished from other autonomic, sensory, and motor nerves.
      A large sympathetic nerve bundle lateral to the internal carotid artery in the
      cavernous sinus gave off one or more branches that leave the artery to encircle
      the abducens nerve. Further division occurs within the cavernous sinus, but all
      sympathetic nerve fibers destined for the orbit entered it through the superior
      orbital fissure. None pass through the optic canal. In the orbit, sympathetics
      were associated with the ophthalmic artery and some of its branches and with the
      sensory root to the ciliary ganglion. After entering the ganglion, the
      sympathetic fibers were lost to detection in most specimens, but they were again
      seen in a single short ciliary nerve in one instance. Sympathetic nerve fibers
      were not detected adjacent to several structures identified in the human anatomy
      literature, such as the intracranial and intracanalicular segments of the
      ophthalmic artery, the nasociliary nerve, the long ciliary nerves, the nerve to
      the inferior oblique muscle, or the lacrimal artery and nerve.

PMID- 1348182
TI  - The autumn greening of Cold Spring Harbor. The Molecular Biology of Signal
      Transduction in Plants. Cold Spring Harbor, NY, USA, October 2-6, 1991.

PMID- 1348183
TI  - Developing in a family way. Transforming Growth Factor Type beta and Related
      Proteins in Development: the Sixth Molecular, Cellular and Developmental
      Biology/Iowa State University Symposium, Ames, IA, USA September 20-23, 1991.
AB  - We are left with the impression that members of the TGF-beta family are
      critically positioned in a cascade of events regulating complex developmental
      processes. Roberts described the TGF-betas as providing the cells with cues to
      their temporal positions in a developmental program, that is, telling the cells
      "where they were, where they are, and where they're going." The broad diversity
      of cellular and tissue responses to TGF-betas and the widespread expression of
      their receptors suggest the TGF-betas may act as a "common currency," enabling
      diverse cell types to communicate with each other. Other members of the family
      are more restricted in their expression and the expression of their receptors,
      and may have a more limited and well-defined developmental role. The complex
      regulation of the members of the TGF-beta family is consistent with their
      importance as directors and coordinators of complicated physiological processes
      such as those occurring in the development of multicellular organisms. Their
      expression is highly regulated at the transcriptional and post-transcriptional
      levels, and their localization and activation can be affected by binding proteins
      and matrix proteins. We still have much to learn about the receptors for this
      family of growth factors, but the recent cloning of the activin and TGF-beta
      receptors and the discovery of their enzymatic nature has dramatically opened the
      way for future studies to resolve the signal transduction pathway(s) used by
      members of this family.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348184
TI  - Hole-istic science. Pore-Forming Toxins and Their Role in the Competition Among
      Different Organisms. Trento, Italy, September 26-29, 1991.

PMID- 1348185
TI  - Trans-regulation of homeotic genes in Drosophila.
AB  - Homeotic genes of the Antennapedia and bithorax complexes control Drosophila
      development by encoding DNA-binding proteins that regulate the transcription of
      target genes. Because either the presence or absence of these DNA-binding
      proteins alters development, regulation of the spatial patterns of expression is
      crucial to normal development. Numerous gene products are required for properly
      regulated expression of Antennapedia and bithorax complex genes, but few (if any)
      are dedicated solely to the regulation of these genes. One of the pleiotropic
      activators of homeotic genes in Drosophila, the brahma gene, encodes a protein
      similar to a yeast protein that is required for transcriptional activation of
      multiple tightly regulated genes. Other components of this system may be
      conserved as well, suggesting that the biochemical basis for induced gene
      expression in single-celled organisms may have more in common with programmed
      developmental pathways in multicellular organisms than previously thought.

PMID- 1348186
TI  - Desensitization of the isolated beta 2-adrenergic receptor by beta-adrenergic
      receptor kinase, cAMP-dependent protein kinase, and protein kinase C occurs via
      distinct molecular mechanisms.
AB  - Exposure of beta 2-adrenergic receptors (beta 2ARs) to agonists causes a rapid
      desensitization of the receptor-stimulated adenylyl cyclase response.
      Phosphorylation of the beta 2AR by several distinct kinases plays an important
      role in this desensitization phenomenon. In this study, we have utilized purified
      hamster lung beta 2AR and stimulatory guanine nucleotide binding regulatory
      protein (Gs), reconstituted in phospholipid vesicles, to investigate the
      molecular properties of this desensitization response. Purified hamster beta 2AR
      was phosphorylated by cAMP-dependent protein kinase (PKA), protein kinase C
      (PKC), or beta AR kinase (beta ARK), and receptor function was determined by
      measuring the beta 2AR-agonist-promoted Gs-associated GTPase activity. At
      physiological concentrations of Mg2+ (less than 1 mM), receptor phosphorylation
      inhibited coupling to Gs by 60% (PKA), 40% (PKC), and 30% (beta ARK). The
      desensitizing effect of phosphorylation was, however, greatly diminished when
      assays were performed at concentrations of Mg2+ sufficient to promote receptor
      independent activation of Gs (greater than 5 mM). Addition of retinal arrestin,
      the light transduction component involved in the attenuation of rhodopsin
      function, did not enhance the uncoupling effect of beta ARK phosphorylation of
      beta 2AR when assayed in the presence of 0.3 mM free Mg2+. At concentrations of
      Mg2+ ranging between 0.5 and 5.0 mM, however, significant potentiation of beta
      ARK-mediated desensitization was observed upon arrestin addition. At a free Mg2+
      concentration of 5 mM, arrestin did not potentiate the inhibition of receptor
      function observed on PKA or PKC phosphorylation. These results suggest that
      distinct pathways of desensitization exist for the receptor phosphorylated either
      by PKA or PKC or alternatively by beta ARK.

PMID- 1348187
TI  - Structure of a ricin mutant showing rescue of activity by a noncatalytic residue.
AB  - Ricin A chain is an N-glycosidase which removes a single adenine base from a
      conservative loop of 28S rRNA, thereby inactivating eukaryotic ribosomes. The
      mechanism of action has been proposed to include transition-state stabilization
      of an oxycarbonium ion on the substrate ribose by interaction with Glu 177.
      Conversion of Glu 177 to Gln reduces activity nearly 200-fold [Ready, M. P., Kim,
      Y., & Robertus, J. D. (1991) Proteins: Struct., Funct., Genet. 10, 270-278] while
      conversion to Ala (E177A) reduces activity only 20-fold [Schlossman, D., Withers,
      D., Welsh, P., Alexander, A., Robertus, J., & Frankel, A. (1989) Mol. Cell. Biol.
      9, 5012-5021]. X-ray analysis of the latter mutant protein shows that a residue
      at the edge of the active site, Glu 208, rotates into the space left vacant by
      the mutation. Its rearranged carboxylate partially substitutes for that of Glu
      177. This is equivalent to the rescue of enzyme activity by a second-site
      reversion. Kinetic analysis shows the E177A mutation affects kcat and not Km,
      consistent with the notion that the carboxylate serves in transition-state
      stabilization.

PMID- 1348188
TI  - Specificity and kinetics of Rhodotorula gracilis D-amino acid oxidase.
AB  - D-Amino acid oxidase purified from the yeast Rhodotorula gracilis is a
      flavoenzyme which does not require exogenous FAD for maximum activity. The enzyme
      showed temperature and pH activity optima centred between 40 and 45 degrees C and
      between 8.0 and 8.5, respectively; a broad pH and ionic strength range of
      stability and a more limited range of thermostability was determined. The enzyme
      stability was markedly influenced by the presence of 2-mercaptoethanol. Apparent
      kinetic parameters for a number of substrates were determined: nonpolar and
      aromatic D-amino acids appeared to be the best substrates. Steady state
      measurements carried out at different oxygen concentrations indicated that for D
      alanine the kinetic pattern is consistent with a Ping Pong Bi Bi mechanism; kcat
      values on D-alanine and D-valine are 43,250 min-1 and 31,370 min-1, respectively.
      L-Amino acids did not inhibit enzyme activity; several aromatic and aliphatic
      carboxylic acids proved to be competitive inhibitors of the enzyme and their ki
      values were determined. The reported properties of R. gracilis D-amino acid
      oxidase markedly distinguish it from other characterized D-amino acid oxidases.

PMID- 1348190
TI  - The revised CDC case definition.

PMID- 1348189
TI  - Congenital dyserythropoiesis and progressive alopecia in Polled Hereford calves:
      hematologic, biochemical, bone marrow cytologic, electrophoretic, and flow
      cytometric findings.
AB  - Congenital dyserythropoiesis with dyskeratosis is a slow, progressive, and often
      fatal disease in Polled Hereford calves. Affected calves have a macrocytic
      normochromic anemia with a mild reticulocytosis. Studies indicate that calves are
      hyperferremic with increased saturation of serum total iron binding capacity,
      which rules out iron deficiency as a cause. Other secondary causes of
      dyserythropoiesis, including cobalamin and folate deficiencies, are unlikely
      because serum cobalamin and folate levels of affected calves were normal. Virus
      isolation was negative, and failure to identify bovine retroviral antigens or
      antibodies from several calves suggested that viral agents were not involved.
      Bone marrow cytologic findings were similar to those in congenital hereditary
      dyserythropoiesis in humans and included occasional multinucleate cells,
      internuclear chromatin bridging between nuclei of partially divided cells, and,
      more frequently, irregular nuclear shapes and chromatin patterns. DNA content and
      cell cycle distribution of erythroid cells appeared normal, and no
      electrophoretic abnormalities were detected in erythrocyte membrane proteins. The
      Polled Hereford syndrome is similar in many ways to type I congenital
      dyserythropoiesis in humans and may be an appropriate biomedical model for
      studying erythroid proliferation during dyserythropoiesis.

PMID- 1348191
TI  - Polymer encapsulated neurotransmitter secreting cells. Potential treatment for
      Parkinson's disease.
AB  - Parkinson's disease, a neurologic disorder characterized by a dopamine deficit
      within the striatum, may be improved by transplantation of polymer encapsulated
      neurosecretory cells. Surrounding cells with a selectively permeable barrier
      offers several advantages, including preventing immune rejection and tumor
      formation while allowing functional efficacy. Bovine adrenal medullary chromaffin
      cells, or PC12 cells, a rat-derived pheochromocytoma cell line, were encapsulated
      within polyelectrolyte-based microcapsules or thermoplastic-based macrocapsules.
      Histologic and biochemical analyses revealed that both types of cells survived
      and that neurotransmitter release from capsules was sustained for several months
      in vitro, irrespective of the encapsulation method employed. Both of the
      encapsulation systems protected the enclosed cells from an immunologic challenge
      in vitro, and prevented immune rejection when cell containing capsules were
      implanted in an immunologically incompatible host. Chromaffin or PC12 cell
      containing capsules implanted into the dopamine (DA) depleted striatum of rats
      reduced the lesion associated functional deficit. These results suggest that
      encapsulated neurosecretory cell implants may be useful in treating various
      central nervous system (CNS) deficits, particularly in cases involving a specific
      neurochemical lesion.

PMID- 1348192
TI  - A magnetically actuated left ventricular assist device.
AB  - Over the past 6 years, research has led to development of a small, lightweight,
      power-efficient, uniquely simple ventricular assist device driven by a magnetic
      actuator. Magnetic actuation permits total elimination of all mechanical motion
      converter components used for pusher plate displacement, resulting in a
      significant reduction in complexity and resultant increase in reliability.
      Extensive in vitro mock loop development has resulted in a left ventricular
      assist device (LVAD), the primary design parameters of which for the clinical
      prototype actuator and pump are 1) an actuator weight of 312 g, 2) actuator size
      of 32.5 cm3, 3) power requirements of 7.8 to 11.4 watts (60-100 beats per minute
      [BPM]), and 4) system efficiency of 24% to 34% and average dynamic stroke volume
      of 65 ml. Initial in vivo tests assessed this LVAD's performance in four sheep
      under three acute conditions of ventricular dysfunction. The results demonstrate
      that, at a pump-rate of 100 BPM, mean aortic pressure increased by 45-50 mmHg
      during 1) beta blockade, 2) coronary ligation, and 3) ventricular fibrillation.
      Pump flow ranged from 2.71 L/min to a maximum of 4.6 L/min. Acute test periods
      were arbitrarily set for 6 hours duration. Of the four sheep, two survived, one
      lived 5 hours, and the fourth lived 4.5 hours. Global fibrillation was the
      primary cause of failure. This initial in vivo data demonstrates the pump's
      ability to maintain satisfactory hemodynamic parameters of flow and pressure
      under three acute conditions of extreme left ventricular dysfunction in an animal
      model. These initial LVAD performances were encouraging. Further tests will use
      calves with a greatly expanded performance evaluation protocol.

PMID- 1348193
TI  - Parkinsonism treatment: Part III--Update.
AB  - OBJECTIVE: The purpose of this review is to update clinicians with recent
      advances in the management of parkinsonism, including drug therapy,
      transplantation, and diet. DATA SOURCES: Pertinent articles were obtained from an
      English-language literature search using MEDLINE (1970-1991), Index Medicus (1987
      1991), Current Contents (1990), and bibliographic reviews of review articles.
      Index terms included parkinsonism, selegiline, pergolide, vitamin E, and
      transplantation. Fifty-five articles (representing 85 percent of the complete
      literature search) were selected by multiple reviewers for their contribution to
      the stated purpose. Emphasis was placed on double-blind, placebo-controlled, and
      randomized studies. Data from cited articles were examined by multiple reviewers
      for support of their stated hypothesis and were included as background for
      justification of major points in this article; critical studies were abstracted
      in more detail. RESULTS: New therapeutic measures have been added to the
      treatment of parkinsonism. Selegiline, a monoamine oxidase inhibitor type B, has
      shown beneficial results, especially in early stages. Pergolide, a dopamine
      agonist, may be an efficacious alternative to bromocriptine resistance or
      intolerable adverse effects. Vitamin E may have protective antioxidant
      properties, but very few clinical data are available. Fetal tissue
      transplantation needs continued research and remains very controversial. Diet
      modification may maximize the results of therapy with exogenous dopamine therapy.
      CONCLUSIONS: Clinicians should familiarize themselves with new alternatives for
      the management of parkinsonism in order to be reliable consultants for both
      professional and lay persons.

PMID- 1348194
TI  - Long-term use of neuroleptics among elderly in a Swedish community.
AB  - OBJECTIVE: Analysis of long-term use of neuroleptics among the elderly in a
      Swedish community. DESIGN: Cohort study, three-year follow-up period. SETTING:
      Primary care. PATIENTS: All people aged 65 years or older who used neuroleptics
      in 1984. RESULTS: Neuroleptic use was fairly common among elderly and continued
      long-term use was relatively frequent. One third of long-term users obtained
      doses exceeding a recommended dosage range. Prescribed doses were seldom changed
      during the study period. CONCLUSIONS: The high proportion of long-term users and
      the stability of the prescribed doses indicate that there is a need for more
      information to be made available to prescribes regarding the risks of long-term
      use of neuroleptics in primary care.

PMID- 1348195
TI  - Improved biocompatibility of bioprosthetic heart valves by L-glutamic acid
      treatment.
AB  - Treatment of glutaraldehyde-fixed pericardium with L-glutamic acid and storage in
      bacteriostatic preservatives (paraben) stably antagonizes free, reactive aldehyde
      groups within the fixed bioprosthetic heart valve tissue. In 63-day subcutaneous
      implants in rats, the calcification rate of this treatment (13.3 +/- 2 mg
      calcium/g wt tissue) was markedly reduced as compared to conventionally treated
      tissue (169 +/- 24 mg/g; p less than 0.05). To test the influence of tissue
      released toxic aldehydes on spontaneous endothelial cell ingrowth in vivo,
      vascular grafts (8-cm long, 6-mm diameter) from fixed pericardium treated with L
      glutamic acid were interposed into the carotid arteries in ten sheep. They were
      compared to grafts from conventionally treated pericardium implanted at the
      contralateral side. Following 3 months of implantation, planimetry revealed 49%
      +/- 20% of the surface of conventionally preserved pericardium to be covered with
      red thrombus, but only 12% +/- 5% in L-glutamic acid treated pericardium (p less
      than 0.05). The ultrastructural findings of a closed endothelial cell layer on
      the graft surface reveals the new technique to be a promising approach towards
      increased biocompatibility of aldehyde-fixed bioprosthetic heart valves.

PMID- 1348196
TI  - Endothelial cell lining of bioprosthetic heart valve material.
AB  - In this in vitro study, the growth properties of cultured endothelial cells on
      conventionally treated pericardial valve material were measured. These data were
      compared to endothelial cell proliferation on an alternatively treated valve
      material. This alternative preservation procedure was developed in order to bind
      free, residual glutaraldehyde in the valve tissue by reaction with L-glutamic
      acid. In order to optimize endothelial cell attachment and proliferation,
      fibronectin and fibrillar collagen type I were tested as surface precoating
      substances. Cell viability of the seeded cells was evaluated by means of
      proliferation kinetics, antithrombotic activity, and morphological appearance.
      Endothelial cell death occurred within the first 2 days after seeding on
      conventionally treated valve tissue, independent of the type of precoating. On
      alternatively treated tissue, regular endothelial cell proliferation was
      observed. Precoating with fibrillar collagen markedly increased endothelial cell
      attachment and proliferation as compared to fibronectin. Maintenance of
      antithrombotic activity of the seeded cells was proven by regular release of
      prostacyclin.

PMID- 1348197
TI  - New developments in the pharmacological treatment of schizophrenia.
AB  - The ability to use pharmacological treatment for schizophrenia is progressing in
      a most efficacious fashion, while the risk of adverse effects is declining. An
      important reevaluation of minimal effective antipsychotic drug dosages for both
      acute and extended treatment has taken place. Clozapine has provided clinical
      practitioners with a useful new alternative for treatment-refractory patients,
      and new research has helped clarify the role of different maintenance and
      prophylactic medication strategies. The author summarizes recent progress in
      these areas.

PMID- 1348199
TI  - Sulphasalazine therapy in rheumatoid arthritis: qualitative changes in
      lymphocytes and correlation with clinical response.
AB  - Clinical and immunological parameters in 14 patients with rheumatoid arthritis
      (RA) receiving sulphasalazine (SASP) were evaluated, to determine whether their
      clinical response was reflected by any quantitative changes in their peripheral
      blood lymphocytes after 12 weeks. Whilst disease activity markers fell
      significantly, no such changes were noted in the percentage or absolute numbers
      of lymphocytes or their subsets. The lymphocytes of a further 21 patients before
      and after receiving SASP for 12 weeks were then studied qualitatively. The
      suppression mediated by in vitro SASP on ex vivo PHA stimulated lymphocytes
      showed a decrease at 12 weeks. This change was more marked and reached
      statistical significance only in those patients who showed a good clinical
      response. It is postulated that this may in some way be related to expression of
      activation markers and concomitant SASP binding.

PMID- 1348198
TI  - Long-term second-line treatment: a prospective drug survival study.
AB  - The long-term use of second-line antirheumatic drugs was prospectively studied in
      a consecutive sample of 245 patients with recently diagnosed rheumatoid
      arthritis. A survival analysis was done in which treatment termination due to
      side-effects and to insufficient therapeutic effect were used as index causes.
      Cumulative drug 'survival' of aurothioglucose with treatment termination due to
      toxicity was significantly less compared with hydroxychloroquine. With regard to
      lack of efficacy as index cause, the administration time of hydroxychloroquine
      was significantly less than that of either aurothioglucose or sulphasalazine.
      Treatment termination due to lack of efficacy or combined insufficient
      therapeutic response and toxicity proved to be influenced by the initial disease
      activity and by the rank order of prescription.

PMID- 1348200
TI  - Undergraduate education in musculoskeletal diseases.

PMID- 1348201
TI  - Pylorus-preserving versus standard pancreatico-duodenectomy: an analysis of 110
      pancreatic and periampullary carcinomas.
AB  - Pylorus-preserving pancreaticoduodenectomy (PPPD) has received increasing
      attention as a physiological alternative to the standard pancreaticoduodenectomy
      (PD) in patients with adenocarcinoma of the pancreatic head or the periampullary
      region. We evaluated mortality, morbidity and survival in 110 patients with
      pancreatic carcinoma (n = 53) or periampullary carcinoma (n = 57). In each group
      31 patients underwent PD, the remainder PPPD. There were no differences in age,
      sex and tumour stage (UICC 1987) between patients undergoing PPPD or PD. Median
      follow-up was 24 months. There were no significant differences in mortality and
      morbidity rates between procedures. The mode of resection had no influence on
      survival in patients with periampullary carcinoma. Patients with pancreatic
      carcinoma who underwent PD had a significantly better survival rate compared with
      those who underwent PPPD (P less than or equal to 0.05). This was particularly so
      in patients with stage III tumours (P = 0.007). These data suggest that in
      patients with ductal carcinoma of the head of the pancreas, PD provides better
      survival than PPPD. However, PPPD appears to achieve equivalent results to PD in
      patients with periampullary carcinoma.

PMID- 1348202
TI  - No abdominal drainage after Whipple's procedure.

PMID- 1348204
TI  - Quality issue tackled from all sides during CMA's 4th Leadership Conference.

PMID- 1348203
TI  - Distribution of tyrosine hydroxylase, serotonin, and leu-enkephalin
      immunoreactive cells in the brainstem of a shark, Squalus acanthias.
AB  - The central nervous system location of neurochemicals that are widely distributed
      among extant animals may give us clues to changes that occurred in the brains of
      these animals during evolution. We have been studying the brains of cartilaginous
      fishes, a heterogeneous group whose central nervous system varies considerably.
      Squalus acanthias, the spiny dogfish shark, was chosen to represent the
      squalomorphs, a group of living sharks known to possess many primitive
      characters. The distribution of tyrosine hydroxylase (TH+), serotonin (5-HT+),
      and leu-enkephalin (LENK+) positive cells within the brainstem of Squalus was
      determined by use of antibodies to these substances. All the major raphe groups
      described for mammals were found in Squalus. The 5-HT+ cells in raphe nuclei were
      more uniformly distributed in Squalus than in Heterodontus, the horn shark. Other
      nuclei that were 5-HT+ and LENK+, and that have been identified in mammals,
      included reticularis paragigantocellularis lateralis, a B9 cell group, and
      reticularis magnocellularis. The postcommissural nucleus and pretectal area
      contained 5-HT+ and LENK+ cells. These cells have been described in a
      holocephalian, in teleosts, and in reptiles but not in other elasmobranchs or in
      mammals. Cells that were TH+ were located in prominent A1/A2, A6 (locus
      coeruleus), A9 (substantia nigra), and A10 (ventral tegmental area) cell groups,
      and in a very small A5 group. We conclude that the variation in chondrichthian
      brainstems exceeds that in mammals, and we suggest that this variation is related
      to life-style and the long evolutionary history of these fishes.

PMID- 1348205
TI  - Massive Vancouver conference focuses on tragedy of world's dying children.

PMID- 1348206
TI  - Protective benefits of liver key to successful bowel transplants, surgeon says.

PMID- 1348207
TI  - Evidence for linear extrachromosomal elements mediating gene amplification in the
      multidrug-resistant J774.2 murine cell line.
AB  - Previous studies from our laboratory have demonstrated specific cytogenetic
      alterations accompanying development of colchicine resistance in the J774.2
      murine cell line and in two sublines (J7.Cl-30 and J7.Cl-100). Although gene
      amplification is not observed in the parental J774.2 cell line, a approximately
      35-fold amplification of the gene for p-glycoprotein (mdr) was noted in the J7.Cl
      30 subline (770-fold CLCR) and a approximately 70-fold amplification in the J7.Cl
      100 subline (2500-fold CLCR). In this study, we analyzed the localization and
      organization of the mdr gene. In the colchicine-resistant (CLCR) J7.Cl-30
      subline, the p-glycoprotein domain was observed to reside on differently sized
      extrachromosomal elements. Our results indicate not only circular
      extrachromosomal elements but also linear extrachromosomal elements. By means of
      pulsed-field gel electrophoresis (PFGE), the sizes of the extrachromosomal
      elements were shown to be greater than 2,500 kilobase-pairs (kb), 800 kb, and 400
      kb. In contrast, the J7.Cl-100 subline was characterized by the presence of
      homogeneously staining regions (HSRs). We have noted that with increasing
      colchicine resistance the extrachromosomal elements are replaced by HSRs. Our
      findings of linear elements that appear to be precursors of HSRs may offer a new
      way to interpret different theories of extrachromosomal gene amplification. The
      J7.Cl-30 cell line presents a unique system to analyze further the formation and
      structure of extrachromosomal elements.

PMID- 1348208
TI  - Cytogenetics of multiple endocrine neoplasia syndromes. I. Two different, unique
      clonal chromosome changes in a medullary thyroid carcinoma and in a C-cell
      thyroid hyperplasia.
AB  - In short-term cultures of tumor tissue from a medullary thyroid carcinoma (MTC),
      we found a large clone of cells with a balanced translocation t(9;12)(p24;q22). A
      large clone with a balanced translocation t(10;16)(p11;q24) was also found in
      cultures from a C-cell thyroid hyperplasia. No clearcut evidence for chromosome
      instability was observed in the lymphocytes of the two patients. The mother of
      the first patient died of MTC; two relatives of the second patient had MTC and
      one of them had pheochromocytoma. These findings classify the two subjects as MEN
      2A patients with different phenotypic expression but with the same type of
      chromosomal abnormality.

PMID- 1348209
TI  - Clonal selection: in the beginning a cell was chosen.

PMID- 1348210
TI  - Patient tolerance of ioxaglate and iopamidol in internal mammary artery
      arteriography.
AB  - To compare discomfort caused by ioxaglate and iopamidol, 25 patients scheduled
      for coronary angiography including internal mammary arteriography were studied.
      Each patient received both agents. Data were available on 22 randomly selected
      patients who completed the protocol. Two patients were withdrawn because of
      unsuccessful internal mammary artery cannulation and one because of idiosyncratic
      reaction to diazepam. After the internal mammary artery injections, the short
      form McGill Pain Questionnaire (SF-MPQ) was completed to evaluate the patient
      response. Ioxaglate caused significantly less discomfort than iopamidol. Word
      scale (WS) p less than .05; visual analog scale (VAS) p less than .05. We
      conclude that ioxaglate is much better tolerated than iopamidol in internal
      mammary arteriography.

PMID- 1348211
TI  - Atresia of the left main coronary artery: clinical recognition and surgical
      treatment.
AB  - Atresia of the left main coronary artery is an extremely rare anomaly with very
      few cases presented in the literature. Even more uncommon are reports of
      successful surgical repair. This article concerns two cases of atresia of the
      left main coronary artery treated surgically with a favourable outcome. The two
      patients (a 16 year-old boy and a 43 year-old woman) had a different clinical
      presentation but identical angiographic and morphologic features. The authors
      examine the embryogenetic defect underlying this anomaly. The differential
      diagnosis involves two congenital malformations (single coronary artery and
      anomalous origin of the left coronary artery from the pulmonary trunk) and
      acquired atherosclerotic disease of the left main coronary artery; the
      distinguishing features of these conditions are reviewed. Surgical management by
      means of internal mammary artery revascularization is discussed in light of
      recent reports about adequacy of blood flow in internal mammary artery bypass
      grafts.

PMID- 1348212
TI  - Right internal mammary artery graft angioplasty through a right brachial artery
      approach using a new custom guide catheter: a case report.
AB  - Angioplasty of right internal mammary artery grafts may present problems because
      of the variable origin of the mammary artery and its angulation from the
      subclavian artery. We report a case of successful angioplasty using a custom
      designed guide catheter, after failed attempts using conventional guide
      catheters.

PMID- 1348213
TI  - Developmental defects in Gorlin syndrome related to a putative tumor suppressor
      gene on chromosome 9.
AB  - Gorlin syndrome is an autosomal dominant disorder that predisposes to basal cell
      carcinomas of the skin, ovarian fibromas, and medulloblastomas. Unlike other
      hereditary disorders associated with cancer, it features widespread developmental
      defects. To investigate the possibility that the syndrome is caused by mutation
      in a tumor suppressor gene, we searched for loss of heterozygosity in 16 sporadic
      basal cell carcinomas, 2 hereditary basal cell carcinomas, and 1 hereditary
      ovarian fibroma and performed genetic linkage studies in five Gorlin syndrome
      kindreds. Eleven sporadic basal cell carcinomas and all 3 hereditary tumors had
      allelic loss of chromosome 9q31, and all informative kindreds showed tight
      linkage between the Gorlin syndrome gene and a genetic marker in this region.
      Loss of heterozygosity at this chromosomal location, particularly in hereditary
      tumors, implies that the gene is homozygously inactivated and normally functions
      as a tumor suppressor. In contrast, hemizygous germline mutations lead to
      multiple congenital anomalies.

PMID- 1348214
TI  - The paired box gene pox neuro: a determinant of poly-innervated sense organs in
      Drosophila.
AB  - This study describes the structure and function of pox neuro (poxn), a gene
      previously isolated by virtue of a conserved domain, the paired box, which it
      shares with the segmentation genes paired and gooseberry. Its expression pattern
      has been analyzed, particularly during development of the PNS. We propose that
      poxn is a "neuroblast identity" gene acting in both the PNS and the CNS on the
      basis of the following evidence. Its expression is restricted to four neuronal
      precursors in each hemisegment: two neuronal stem cells (neuroblasts) in the CNS,
      and two sensory mother cells (SMCs) in the PNS. The SMCs that express poxn
      produce the poly-innervated external sense organs of the larva. In poxn- embryos,
      poly-innervated sense organs are transformed into mono-innervated. Conversely,
      ectopic expression of poxn in embryos transformed with a heat-inducible poxn gene
      can switch mono-innervated to poly-innervated sense organs. Expression of poxn in
      the wing disc is restricted to the SMCs of the poly-innervated sense organs,
      suggesting that poxn also determines the lineage of poly-innervated adult sense
      organs.

PMID- 1348215
TI  - Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that induces
      differentiation of mammary tumor cells.
AB  - The neu/HER-2 proto-oncogene (also called erbB-2) encodes a transmembrane
      glycoprotein related to the epidermal growth factor receptor. We have purified to
      homogeneity a 44 kd glycoprotein from the medium of ras-transformed cells that
      stimulates phosphorylation of the Neu protein and retains activity after elution
      from the polyacrylamide gel. The protein is active at picomolar concentrations
      and displays a novel N-terminal sequence. Cross-linking experiments with
      radiolabeled p44 result in specific labeling of Neu, indicating that p44 is a
      ligand for Neu or a related receptor. The purified protein induces phenotypic
      differentiation of cultured human breast cancer cells, including altered
      morphology and synthesis of milk components. This is accompanied by an increase
      in nuclear area, inhibition of cell growth (probably by cell cycle arrest at the
      late S or the G2/M phases), and induction of DNA polyploidy. We propose the name
      Neu differentiation factor (NDF) for p44.

PMID- 1348216
TI  - Effects of beta-2 microglobulin anti-sense oligonucleotides on sensitivity of
      HER2/neu oncogene-expressing and nonexpressing target cells to lymphocyte
      mediated lysis.
AB  - The mechanism by which HER2/neu overexpressing tumor cells resist NK, LAK, and
      LDCC cytotoxic lymphocytes was investigated. Resistance was not explained by a
      delay in kinetics of lysis, concurrent resistance to TNF, or a diminished
      expression of the transferrin receptor. HLA-class I expression, however, was
      markedly elevated compared to HER2 nonexpressing targets suggesting a reason for
      resistance. To test the role of class I, we selectively decreased expression by
      incubation of targets with beta-2 microglobulin anti-sense oligonucleotides. Anti
      sense-treated HER2+ targets, displaying levels of class I comparable to HER2-
      targets, were still markedly resistant to cytotoxic effectors. Down-regulation of
      class I expression in HER2- carcinoma cells also had no effect on sensitivity to
      cytotoxicity by anti-sense treatment of Raji and U937 targets resulted in
      enhanced sensitivity to NK and LAK effectors but not to T cells mediating LDCC.
      These data indicate resistance to cytotoxicity in HER2-expressing targets cannot
      be solely explained by heightened expression of class I. The data also support
      the concept that class I expression regulates sensitivity to NK and LAK cells
      (but not LDCC effectors) in selected targets.

PMID- 1348217
TI  - Activation of noradrenergic and nitrergic mechanisms in the rat anococcygeus
      muscle by nicotine.
AB  - 1. Nicotine (10 mumol/L) produced rapidly developing but transient contractions
      of anococcygeus muscle isolated from rats. The magnitude of the response varied
      considerably between preparations. Tachyphylaxis occurred, such that no response
      was elicited by the same or a larger concentration in the continued presence of
      10 mumol/L nicotine. 2. Contractions produced by nicotine were not affected by
      atropine, but were abolished by Hexamethonium and the alpha-adrenoceptor
      antagonists prazosin and phentolamine. Contractions were absent in the
      anococcygeus muscles of rats pretreated with reserpine. 3. The alpha 2
      adrenoceptor agonist UK14304, or guanethidine, raised the tone of the
      anococcygeus muscle, and converted responses to field stimulation and nicotine to
      relaxations. Nicotine-induced relaxations were more pronounced in the presence of
      UK14304 than guanethidine. 4. Relaxations produced by nicotine (1-18 mumol/L)
      were transient, and tachyphylaxis occurred. When precautions were taken to avoid
      tachyphylaxis, concentration-response curves could be constructed. The
      relaxations elicited by nicotine were abolished or greatly reduced by
      hexamethonium, tetrodotoxin or omega-conotoxin GVIA. 5. The nitric oxide synthase
      inhibitor L-NG-nitroarginine methyl ester (90 mumol/L) enhanced contractile
      responses to field stimulation and nicotine, and markedly reduced relaxations
      elicited by field stimulation and nicotine in the presence of UK14304. These
      relaxations were restored by L-arginine (270 mumol/L). 6. The results suggest
      that nicotine acts on nicotinic receptors of noradrenergic and nitrergic nerve
      terminals in the rat anococcygeus muscle, resulting in the release of
      noradrenaline and nitric oxide respectively.

PMID- 1348218
TI  - Breath-holding in panic disorder.
AB  - In earlier studies, it was found that exogenous carbon dioxide administration
      provoked high anxiety in panic disorder (PD) patients, whereas healthy normals
      and patients suffering from other anxiety disorders were hardly affected. Breath
      holding provides a simple method to induce endogenous CO2 accumulation. Fourteen
      PD patients, 14 patients suffering from other anxiety disorders, and 14 healthy
      controls were asked to hold their breath as long as possible. Apnea times
      appeared to be longer in the normal control group than in the other two groups.
      Using a one-tailed t test, a trend for a difference was found between the PD
      subjects and other anxiety patients, the PD patients having slightly lower
      values. No differences were found with respect to increase in anxiety during
      breath-holding or the ratio of apnea times before and after hyperventilation.

PMID- 1348219
TI  - Formoterol, a new long-acting beta 2 agonist, inhaled twice daily, in stable
      asthmatic subjects.
AB  - STUDY OBJECTIVE: To determine whether formoterol, a new beta 2 agonist with
      experimentally documented long duration, is clinically more effective than
      salbutamol in the maintenance treatment of chronic asthma. DESIGN: Randomized
      double-blind between-patient comparison between treatment with formoterol and
      with salbutamol during four weeks. SETTING: Asthma/allergy department in a
      university hospital. PATIENTS: Thirty-seven patients with chronic stable asthma,
      who during a two-week run-in period with inhaled salbutamol, 4 x 100 micrograms
      twice a day, used at least four additional doses (100 micrograms each) daily,
      were randomly assigned to use either formoterol or salbutamol. Thirty-five
      patients were evaluated for efficacy. One early withdrawal and one dropout were
      found in the salbutamol group. The groups were similar with respect to
      demographic data and baseline lung function. INTERVENTIONS: During the four-week
      study period, the patients used either formoterol (4 x 6 micrograms twice a day
      and as necessary, n = 19) or salbutamol (4 x 100 micrograms twice a day and as
      necessary, n = 16). Inhaled steroids and orally administered theophylline were
      allowed if doses were kept constant. MEASUREMENTS AND MAIN RESULTS: The median
      number of additional doses per 24 h (median of two weeks) of the test aerosols
      was 0 (range, 0 to 6) for formoterol and 4 (range, 0 to 14) for salbutamol (p
      less than 0.01). Morning and evening PEFRs were 422 (SEM = 31) and 443 (SEM =
      30), respectively, for formoterol, and 335 (SEM = 30) and 360 (SEM = 26),
      respectively, for salbutamol (p = 0.05 for both). Formoterol was superior (p less
      than 0.05) to salbutamol with respect to control of asthma symptoms, estimated
      duration of action and patient preference. Side effects did not differ.
      CONCLUSIONS: Inhaled formoterol administered twice a day and as necessary was
      clinically more effective than the same regimen of salbutamol.

PMID- 1348220
TI  - Sulfasalazine-induced pulmonary disease.
AB  - We report the findings in two patients with sulfasalazine-induced pulmonary
      disease. The first patient developed pulmonary interstitial fibrosis after more
      than 4 yr of treatment for Crohn's disease. Pulmonary symptoms and chest
      roentgenographic and pulmonary function abnormalities gradually reversed after
      stopping the drug. No specific treatment was given. The second patient, who had
      rheumatoid arthritis without pulmonary disease, received the drug for 1 yr
      without experiencing any problems. Readministration seven months later resulted
      in the development of an acute interstitial pulmonary disease. Discontinuing the
      drug and treatment with corticosteroids produced rapid improvement. We discuss
      these patients in relation to other reports of sulfasalazine-induced pulmonary
      toxicity, highlighting their atypical features.

PMID- 1348221
TI  - Atrial fibrillation 1992. Management strategies in flux.

PMID- 1348222
TI  - Thrombolysis in cardiopulmonary disease. 57th ACCP assembly. San Francisco.

PMID- 1348224
TI  - Neurochemical regulation of oxytocin secretion in lactation.

PMID- 1348223
TI  - Potentiation of bromobenzene-induced pneumotoxicity by phenobarbital as
      determined by bronchoalveolar lavage fluid analysis.
AB  - Bromobenzene produces pulmonary, renal and hepatic damage in the rat.
      Phenobarbital potentiates bromobenzene-induced hepatotoxicity. Studies were
      initiated to determine if phenobarbital potentiates the pulmonary damage produced
      by bromobenzene. In a dose ranging study, adult male rats were treated daily for
      4 days with phenobarbital (80 mg/kg, ip) and on the fifth day were dosed with 0,
      2, 3, or 4 mmoles/kg, ip, bromobenzene. In a larger study phenobarbital was given
      for 4 days (80 mg/kg, ip), and bromobenzene (3.3 mmoles/kg, ip) was given on the
      fifth day. Pulmonary damage was assessed 24 hours later in the first study and 12
      hours later in the second study by bronchoalveolar lavage fluid analysis (BALF),
      microsomal mixed function oxidase measurements and histopathological evaluations.
      BALF biochemical markers employed were gamma-glutamyl transpeptidase (GGT),
      lactate dehydrogenase (LDH) and total protein. Phenobarbital treatment greatly
      enhanced bromobenzene-induced GGT and LDH release into the lavage fluid in a dose
      dependent manner. Phenobarbital treatment increased microsomal 7-O-dealkylation
      of both ethoxy- and pentoxyresorufin in the liver without affecting these
      activities in the lung. Bromobenzene treatment decreased the hepatic microsomal
      dealkylation of decreased the hepatic microsomal dealkylation of pentoxyresorufin
      in a dose-dependent manner. Since known rat pulmonary P450 isozymes have been
      reported to be insensitive to phenobarbital induction, it may be that the
      toxicity is due to transport of a reactive metabolite(s) formed in the liver to
      the lung or bromobenzene is activated by some other pulmonary P450 isozyme
      responsive to phenobarbital.

PMID- 1348225
TI  - Contemporary aspects of discrete peak-detection algorithms. II. The paradigm of
      the luteinizing hormone pulse signal in women.

PMID- 1348227
TI  - Both beta 1- and beta 2-adrenoceptors are involved in mediating
      phosphatidylcholine secretion in rat type II pneumocyte cultures.
AB  - A primary culture of rat type II pneumocytes was used for the pharmacological and
      functional characterization of beta-adrenoceptor subtypes. The beta-adrenoceptor
      agonists, isoprenaline, dobutamine and procaterol concentration dependently
      increased the secretion of phosphatidylcholine. These effects were attenuated by
      propranolol. The effect of dobutamine was attenuated by atenolol, and that of
      procaterol by ICI 118,551. Isoprenaline-induced secretion was attenuated by the
      combination of the two blockers but not by each one alone. In conclusion, both
      beta 1- and beta 2-adrenoceptor subtypes mediate phosphatidylcholine secretion in
      rat type II pneumocytes.

PMID- 1348226
TI  - Coronary heart disease risk factors before and after bypass surgery: results of a
      controlled trial on multifactorial rehabilitation.
AB  - The effect of a three-phase multifactorial institution-based rehabilitation
      programme on coronary heart disease (CHD) risk factors was studied in an open
      randomised trial comprising 228 patients undergoing coronary artery bypass
      surgery allocated into a rehabilitation (R) group (n = 119) and a hospital (H =
      control) group (n = 109). Follow-up examinations were performed at 6 and 12
      months. Serum total cholesterol and triglyceride levels decreased significantly
      in both groups during follow-up. These decreases were not significantly different
      between the R and H groups. Serum high density lipoprotein (HDL) cholesterol
      level increased significantly at 6 and 12 months in the R group, but not in the H
      group. The differences in the changes between the groups were not significant.
      The ratio of serum HDL cholesterol to total cholesterol increased significantly
      in the R group from the preoperative value of 0.154 to 0.179 (P less than 0.001)
      at 6 months and to 0.180 (P less than 0.001) at 12 months. In the H group these
      values were 0.152, 0.166 (P less than 0.001) and 0.168 (P less than 0.001),
      respectively. The significance of the differences in the changes between the
      groups were P = 0.01 at 6 months and 0.06 at 12 months. These differences were
      more obvious in patients aged 55 years or under. There was a significant decrease
      (P = 0.005) in the proportion of smokers in the R group and a significant
      increase in the proportion of patients taking regular exercise in both groups as
      assessed by questionnaire.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348228
TI  - N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, an irreversible receptor
      inactivator, as a tool for measurement of alpha 2-adrenoceptor occupancy in vivo.
AB  - In rats treatment with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)
      induces a dose-dependent decrease in the number of alpha 2-adrenoceptors. Prior
      injection of alpha-adrenergic agents such as yohimbine and clonidine protect
      alpha 2-adrenoceptors against the effects of EEDQ. The ED50 values for yohimbine
      and clonidine were 10.27 and 5.83 mumol/kg, respectively.

PMID- 1348229
TI  - Na(+)-dependent high-affinity uptake of L-glutamate in cultured fibroblasts.
AB  - Uptake of 1 microM [3H]L-glutamate by cultured 3T3 fibroblasts was strongly
      dependent on extracellular Na+; it was reduced by elevated concentrations of K+
      (60 mM) but it was not influenced by variations in the concentration of Ca2+ (0
      9.6 mM). D- and L-Asparate, D- and L-threo-3-hydroxyaspartate DL-threo-3
      methylaspartate and a few other glutamate derivatives and analogues inhibited the
      uptake but several close analogues of L-glutamate (including D-glutamate) had no
      effect, implying that the uptake system is highly structurally selective. The
      recently identified inhibitor of glutamate uptake in synaptosomal preparations, L
      trans-pyrrolidine-2,4-dicarboxylate, was also among the inhibitors. Apparent Km
      of the uptake was found to be less than 10 microM. The present observations
      indicate that Na(+)-dependent 'high-affinity' uptake of L-glutamate may appear in
      structures which are apparently unrelated to glutamatergic synaptic transmission
      in the CNS.

PMID- 1348230
TI  - The effect of ammonia and pH on brain gamma-glutamyl transpeptidase in young
      rats.
AB  - Acute hyperammonemia, induced by two consecutive injections of ammonium acetate
      (550 and 450 mg per kg b.wt.), decreased the activity of gamma-glutamyl
      transpeptidase (GGT) in most brain regions of 18- and 30-day-old rats. This
      decrease in the brain GGT activity was more pronounced in younger than in older
      rats. After the addition of NH4Cl to the incubation medium, the inhibitory action
      of NH4+ on this enzyme activity was also demonstrated in crude synaptosomal
      membranes at pH 7.4, but in a range of NH4+ concentrations many-times higher than
      those found in the plasma or brains of young hyperammonemic rats. Because similar
      concentrations of NH4+ stimulated the activity of the purified enzyme from rat
      kidney (mainly at pH 9.0), the inhibition of GGT activity in the young rat brain
      is probably mediated indirectly and not by a direct interaction of ammonia with
      the enzyme molecules.

PMID- 1348232
TI  - 76th General Meeting of the Japanese Society of Gastroenterology. Tokyo, Japan,
      March 29-31, 1990. Abstracts.

PMID- 1348233
TI  - Sequence and organization of 5S ribosomal RNA-encoding genes of Arabidopsis
      thaliana.
AB  - We have isolated a genomic clone containing Arabidopsis thaliana 5S ribosomal RNA
      (rRNA)-encoding genes (rDNA) by screening an A. thaliana library with a 5S rDNA
      probe from flax. The clone isolated contains seven repeat units of 497 bp, plus
      11 kb of flanking genomic sequence at one border. Sequencing of individual
      subcloned repeat units shows that the sequence of the 5S rRNA coding region is
      very similar to that reported for other flowering plants. Four A. thaliana
      ecotypes were found to contain approx. 1000 copies of 5S rDNA per haploid genome.
      Southern-blot analysis of genomic DNA indicates that 5S rDNA occurs in long
      tandem arrays, and shows the presence of numerous restriction-site polymorphisms
      among the six ecotypes studied.

PMID- 1348231
TI  - Complications associated with ulcer recurrence following gastric surgery for
      ulcer disease.
AB  - The present study is an attempt to assess the risks of the complications
      associated with recurrent ulcers in patients who have undergone gastric surgery
      and to determine whether these risks differ from those observed in patients
      receiving long term maintenance treatment with H2-receptor antagonists for ulcer
      disease. One hundred and thirty studies reported in the literature during the
      past three decades have been analysed to determine both the approximate rate of
      ulcer recurrence and the proportion of patients with recurrent ulcers who have
      presented with either haemorrhage or perforation following the various types of
      gastric surgery for ulcer disease. From these data, estimates of the risks of
      haemorrhage and of perforation during the years following gastric surgery have
      been calculated. Vagotomy and antrectomy is associated with a low risk of ulcer
      recurrence (less than 1%) and the risk of complications in later years is
      accordingly very small (less than 0.5%). Partial gastrectomy, although associated
      with low recurrence rates, has a higher risk of complications (1.3% for
      haemorrhage, 0.3% for perforation) because the proportion of recurrent ulcers
      that present with haemorrhage or perforation is high (33% and 8%, respectively).
      Truncal vagotomy plus drainage (TV + D) and highly selective vagotomy (HSV) are
      associated with recurrence rates of 9% and 12%, respectively, but ulcer
      recurrences following these operations are less frequently accompanied by
      complications then recurrences after gastric resection and, as a result, the
      risks of haemorrhage (1.7% for TV + D; 1.3% for HSV) are similar to the risks
      after gastric resection. During long term (five years or more) maintenance
      treatment with H2-receptor antagonists, the risks of haemorrhage and perforation
      are less than 2% and less than 0.5%, respectively. It appears, therefore, that
      the likelihood of developing haemorrhage or perforation following gastric surgery
      is of the same order as that during maintenance treatment with H2-receptor
      antagonists, at least during the first decade of follow-up.

PMID- 1348234
TI  - Effect of phenoclor DP6 on enzyme-altered foci and lipid peroxidation in livers
      of aflatoxin B1-initiated rats.
AB  - This study investigates the capacity of phenoclor DP6 to promote aflatoxin B1
      (AFB1)-induced putative preneoplastic foci in the liver. In male Sprague-Dawley
      rats pretreated with AFB1 (ip injection of 1 or 2 mg/kg body weight once weekly
      for 3 consecutive wk) and given a diet containing 50 ppm phenoclor DP6 for 11
      days, the number of area of putative liver preneoplastic lesions were increased
      approximately four-fold as indicated by the number and gamma-glutamyl
      transpeptidase activity of enzyme-altered foci; this change was also accompanied
      by an increase in hepatic microsomal lipid peroxidation and a decrease in Se
      glutathione peroxidase and superoxide dismutase activities. The results indicate
      that phenoclor DP6 exerts a promoting effect in AFB1-initiated rats.

PMID- 1348235
TI  - [Primary hypothyroidism in normal thyroid gland morphology].
AB  - A 25 year old patient developed hypothyroidism with antibodies against
      thyroglobulin, thyroid microsomes and thyrotropin receptors. Thyroid 99m
      technetium-uptake was 0%. Ultrasound investigation revealed a normal sized,
      homogenous thyroid gland. Histology showed lymphocyte infiltration but regular
      follicles. These results suggest the cause of hypothyroidism to be thyrotropin
      inhibiting immunoglobulins with no parenchyma-destroying properties.

PMID- 1348236
TI  - Pharmacokinetics of vidarabine in the treatment of polyarteritis nodosa.
AB  - The pharmacokinetics of vidarabine were studied in 8 patients with polyarteritis
      nodosa related to hepatitis B virus infection. The drug was administered by
      continuous infusion for three weeks at doses of 15 (1 week) and 7.5 (2 weeks)
      mg/kg per day, during which time 15 plasma exchanges were performed. Plasma was
      assayed for vidarabine and its principal metabolite, hypoxanthine arabinoside by
      high pressure liquid chromatography. Vidarabine was not detected in the plasma of
      any patients. Hypoxanthine arabinoside levels were used to evaluate vidarabine
      kinetics. The serum levels of hypoxanthine arabinoside ranged from 3.6 to 21.5
      mg/l. The mean elimination half-life (+/- SD) was 3.0 +/- 1.7 h. The plasma
      clearance (mean +/- SD) was 195 +/- 270 ml/min when the dose was 7.5 mg/kg per
      day and 66.3 +/- 47 ml/min for a 15 mg/kg per day/dose (NS). Except for the
      elimination half-life, these results were not fully consistent with those
      observed in other studies. The influence of multiple plasma exchanges on
      vidarabine kinetics is limited and dosage adjustment is not required based on the
      continuous infusion of vidarabine.

PMID- 1348237
TI  - Recent developments in understanding and treating drug abuse and dependence.
AB  - Although some progress appears to have been made in curbing the spread of drug
      abuse, it is still widespread in American society. The authors summarize current
      relevant issues in addiction psychiatry. New developments are described in the
      areas of epidemiology, heredity and environmental influences, neuroreceptors and
      neurotransmitters, AIDS, diagnostic classification, psychopathology,
      psychodynamics, new psychotherapeutic approaches, the efficacy of psychotherapy,
      and pharmacologic treatment. New findings confirm the important role of the
      psychiatrist and other mental health practitioners in many aspects of drug abuse
      research and treatment.

PMID- 1348238
TI  - Quality of life of schizophrenic patients on medications and implications for new
      drug trials.
AB  - The quality of life of schizophrenic patients participating in clinical trials of
      new neuroleptics is rarely systematically assessed. Factors that may have
      contributed to the neglect of such assessments include the difficulty of
      measuring changes affecting quality of life during short-term trials and the
      continued belief that schizophrenic patients' self-reports about inner states are
      unreliable. A model of determinants specifically related to the quality of life
      of schizophrenic patients in such trials would include symptoms, side effects of
      neuroleptics, and psychosocial performance. In view of the importance of
      assessing the quality of life of patients on medications, the author recommends
      that regulatory agencies require such assessments in clinical trials of new
      neuroleptics.

PMID- 1348239
TI  - Phorbol ester and atrial natriuretic peptide receptor response on vascular smooth
      muscle.
AB  - At least two types of receptors for natriuretic peptides have been reported:
      biologically active receptors coupled with guanylate cyclase (atrial natriuretic
      peptide [ANP]-B receptors) and clearance receptors (ANP-C receptors). To
      elucidate the role of protein kinase C (PKC) in the regulation of ANP-B
      receptors, vascular smooth muscle cells in culture were treated with phorbol
      ester. Incubation with receptor agonists and phorbol ester led to the
      desensitization of receptor-mediated cyclic guanosine monophosphate (ANP-B
      receptor response) in rat vascular smooth muscle cells. Although a PKC inhibitor
      and downregulation of PKC by long-term incubation of cells with phorbol esters
      blocked the phorbol ester-induced desensitization of the ANP-B receptor response,
      they did not block the ANP-induced desensitization of the ANP-B receptor
      response. In addition, when desensitization by phorbol esters was observed, ANP
      was still capable of desensitization. These observations suggest that the
      mechanism for regulating ANP-B receptor sensitivity may be both PKC-dependent and
      PKC-independent and mediated by phorbol esters and ANP, respectively.

PMID- 1348240
TI  - In vitro and in vivo detection of somatostatin receptors in human malignant
      lymphomas.
AB  - A wide variety of primary and metastatic human neoplasms express somatostatin
      receptors (SS-Rs). We evaluated the SS-R status of malignant lymphomas that had
      been surgically removed from 31 patients by use of in vitro SS-R autoradiography
      with the SS analog 125I-[Tyr3]-octreotide as radioligand. Of 11 low-grade
      malignancy B-cell non-Hodgkin's lymphomas, 10 were SS-R-positive, with a high
      receptor density restricted to the neoplastic follicles. All of the 8
      intermediate-grade lymphomas were SS-R-positive. Of the B-cell lymphomas of high
      grade malignancy, 7 out of 10 were SS-R-positive, often with a high density of
      receptors. One T-cell lymphoma and one Hodgkin's lymphoma were also positive. SS
      Rs were of high affinity (KD = 1.2 nM) and specific for bioactive SS analogs. In
      4 patients, the lymphomas were localized in vivo by use of gamma-camera
      scintigraphy after i.v. injection of the SS analog 111In-[DTPA-D-Phe1]
      octreotide. Hot spots, identified in all 4 patients, corresponded to SS-R
      positive malignant-lymphoma tissue, as confirmed by receptor autoradiography of
      the surgically removed tumors. Our data show that SS-Rs are valuable
      pathobiochemical tissue markers and potentially useful in vivo diagnostic tools
      for human malignant lymphomas.

PMID- 1348241
TI  - Probing daunorubicin accumulation defects in non-P-glycoprotein expressing
      multidrug-resistant cell lines using digitonin.
AB  - Multidrug resistance (MDR) in tumor cells is frequently associated with reduced
      cellular cytostatic drug accumulation, caused by the drug efflux protein, P
      glycoprotein (Pgp). The action of Pgp in tumor cells can be detected by measuring
      the increase of daunorubicin accumulation upon blocking Pgp with drugs such as
      verapamil. A number of MDR cell lines have been described, characterized by
      decreased drug accumulation without Pgp being present. For such non-Pgp MDR cells
      no gene probes or functional assays are available to study this phenotype in
      clinical tumor specimens. We have worked out a method which enables the detection
      of drug-transport-related decreases in cellular daunorubicin accumulations
      without the need for the use of specific Pgp blockers. The cells used were SW
      1573-, GLC4- and HT1080-sensitive cell lines, which accumulated (corrected for
      DNA content) 272%, 1,288% and 203% more daunorubicin than the non-Pgp MDR
      sublines SW-1573/2R120, GLC4/ADR and HT1080/DR4. When the plasma membranes of
      these MDR lines were permeabilized with 20 microM digitonin an increase to 282%,
      1,260% and 239% of 14C-daunorubicin control accumulation was measured (at pH =
      7.35). The intracellular pH measured with BCECF was the same in parent and
      corresponding MDR cells, excluding the role of pH differences in the measured
      effects. This method provides a tool allowing the detection of cellular
      mechanisms (including Pgp) which are related to active outward transport of
      daunorubicin.

PMID- 1348242
TI  - Occurrence of Listeria species in raw milk and dairy products produced in
      Northern Ireland.
AB  - The overall incidence of Listeria spp. in raw milk samples surveyed was found to
      be 25.0% (Listeria monocytogenes 15.3%), with the incidence in samples from
      processing centres 54.0% (L. monocytogenes 33.3%); this was higher than that in
      samples from dairy farms (Listeria spp. 8.8%; L. monocytogenes 5.3%). The FDA
      enrichment procedure was much more productive than cold enrichment and Oxford
      agar was superior to modified McBride agar for isolation of Listeria. Listeria
      monocytogenes was never isolated by direct plating of raw milk samples on Oxford
      agar at a detection level of 1.0 cfu/ml. Listeria spp. were isolated from 1 of 95
      pasteurized milk samples (L. monocytogenes) and 1 of 33 soft cheese samples (L.
      seeligeri). Restriction fragment length polymorphism was more useful than sero-
      or phage-typing for typing of L. monocytogenes strains, and results suggest that
      specific L. monocytogenes strains may persist in both farm and processing
      environments.

PMID- 1348243
TI  - Role of the rfaG and rfaP genes in determining the lipopolysaccharide core
      structure and cell surface properties of Escherichia coli K-12.
AB  - Deletions which removed rfa genes involved in lipopolysaccharide (LPS) core
      synthesis were constructed in vitro and inserted into the chromosome by linear
      transformation. The deletion delta rfa1, which removed rfaGPBI, resulted in a
      truncated LPS core containing two heptose residues but no hexose and a deep
      rought phenotype including decreased expression of major outer membrane proteins,
      hypersensitivity to novobiocin, and resistance to phage U3. In addition, delta
      rfa1 resulted in the loss of flagella and pili and a mucoid colony morphology.
      Measurement of the synthesis of beta-galactosidase from a cps-lacZ fusion showed
      that the mucoid phenotype was due to rcsC-dependent induction of colanic acid
      capsular polysaccharide synthesis. Complementation of delta rfa1 with rfaG+ DNA
      fragments resulted in a larger core and restored the synthesis of flagella and
      pili but did not reverse the deep rough phenotype or the induction of cps-lacZ,
      while complementation with a fragment carrying only rfaP+ reversed the deep rough
      phenotype but not the loss of flagella and pili. A longer deletion which removed
      rfaQGPBIJ was also constructed, and complementation studies with this deletion
      showed that the product of rfaQ was not required for the functions of rfaG and
      rfaP. Thus, the function of rfaQ remains unknown. Tandem mass spectrometric
      analysis of LPS core oligosaccharides from complemented delta rfa1 strains
      indicated that rfaP+ was necessary for the addition of either phosphoryl (P) or
      pyrophosphorylethanolamine (PPEA) substituents to the heptose I residue, as well
      as for the partial branch substitution of heptose II by heptose III. The
      substitution of heptose II is independent of the type of P substituent present on
      heptose I, and this results in four different core structures. A model is
      presented which relates the deep rough phenotype to the loss of heptose-linked P
      and PPEA.

PMID- 1348244
TI  - Purification and partial characterization of transglutaminase from Physarum
      polycephalum.
AB  - An intracellular form of calcium ion-dependent transglutaminase (R
      glutaminylpeptide:amine gamma-glutaminyltransferase, EC 2.3.2.13) was purified
      818-fold to apparent homogeneity from acetone powder preparations of spherules of
      the acellular slime mold Physarum polycephalum. The enzyme was purified by
      combined methods of precipitation with 15% (wt/vol) polyethylene glycol, DEAE
      cellulose chromatography, and isoelectric focusing in a pH 5 to 7 gradient. The
      isoelectric point of the enzyme was 6.1. The molecular mass of the denatured
      enzyme was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      to be 39.6 kDa. A molecular weight of 77,000 was found by gel filtration of the
      native enzyme on a Superose 12 fast protein liquid chromatography column,
      indicating that the native functional protein is a dimer. The purified
      transglutaminase catalyzed the incorporation of [14C]putrescine into protein
      substrates including casein, N,N'-dimethylcasein, actin purified from P.
      polycephalum, and actin purified from bovine muscle. Actin was the preferred
      substrate for the enzyme, both as a purified protein and in crude extracts
      prepared from P. polycephalum. With N,N'-dimethylcasein as the amine acceptor
      substrate, [14C]putrescine, [14C]spermidine, and [14C]spermine were all effective
      amine donor substrates with Km values of 49, 21.4, and 31.7 microM, respectively.
      All three of these polyamines demonstrated strong substrate inhibition of the
      enzyme activity between 100 and 200 microM. Upon starvation induced by depletion
      of a carbon source for growth, the specific activity of this enzyme increased
      sixfold during the differentiation of P. polycephalum microplasmodia to
      spherules. This suggests a role for transglutaminase in the construction of
      spherules, which have the capacity to survive starvation and dessication.

PMID- 1348245
TI  - Peptide transport by the multidrug resistance pump.
AB  - The membrane P-glycoprotein (P170) is an ATP-hydrolyzing transmembrane pump, and
      elevated levels of P170, due to higher expression with or without amplification
      of the multidrug resistance gene (mdr1), result in resistance to a variety of
      chemotherapeutic agents in mammalian cells. The function of the P170 pump has
      been proposed as a protection against toxic substances present in animal diets.
      Here we describe a Chinese hamster ovary cell line that was selected for
      resistance to a synthetic tripeptide, N-acetyl-leucyl-leucyl-norleucinal (ALLN).
      This ALLN-resistant variant shows the classical multidrug resistance (MDR)
      phenotype, including overexpression and amplification of the mdr1 gene.
      Additionally, a mouse embryo cell line overexpressing the transfected mdr1 gene
      is likewise resistant to ALLN. Our results demonstrate that P170 is capable of
      transporting peptides and raise the possibility that the mdr1 gene product or
      other MDR-like genes, present in the genome of mammalian cells, may be involved
      in secretion of peptides or cellular proteins as is the case with the
      structurally similar hylB and ste6 gene products of Escherichia coli and yeast,
      respectively.

PMID- 1348246
TI  - Characterization of the human 5-hydroxytryptamine1B receptor.
AB  - We report the cloning of a human gene encoding the 5-hydroxytryptamine1B
      receptor. The receptor has the characteristics of a G-protein-linked receptor and
      is most homologous to the human 5-HT1D receptor. This human 5-HT receptor gene,
      most abundantly expressed in striatum, is localized on chromosome 6, at 6q13, and
      the gene encoding the 5-HT1D receptor is localized on chromosome 1. Radioligand
      studies indicate that the affinity of [3H]5-HT is 16 +/- 2 nM. Drug competition
      studies indicate that the receptor displays high affinity (i.e. less than 40 nM)
      for 5-HT, 5-carboxyamidotryptamine, methiothepin, and metergoline.

PMID- 1348247
TI  - Essential cysteines in 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from
      Escherichia coli. Analysis by chemical modification and site-directed mutagenesis
      of the phenylalanine-sensitive isozyme.
AB  - The phenylalanine-sensitive isozyme of 3-deoxy-D-arabino-heptulosonate-7
      phosphate synthase from Escherichia coli was inactivated by the sulfhydryl
      modifying reagents 5,5-dithiobis-(2-nitrobenzoate), bromopyruvate, and N
      ethylmaleimide and protected from inactivation by the presence of its metal
      activator, Mn2+, and substrate, phosphoenolpyruvate. Inactivation by 5,5
      dithiobis-(2-nitrobenzoate) was correlated with modification of two of the seven
      cysteine sulfhydryls of the enzyme monomer. The kinetics of 5,5-dithiobis-(2
      nitrobenzoate) modification were altered significantly and distinctively by both
      substrates (phosphoenolpyruvate and erythrose 4-phosphate), by Mn2+, and by L
      phenylalanine, suggesting that ligand binding has significant effects on the
      conformation of the enzyme. Site-directed mutagenesis was used to create multiple
      substitutions at the two invariant cysteine residues of the polypeptide, Cys-61
      and Cys-328. Analysis of purified mutant enzymes indicated that Cys-61 is
      essential for catalytic activity and for metal binding. Cys-328 was found to be
      nonessential for catalytic activity, although mutations at this position had
      significant negative effects on Vmax, KmMn, and KmPEP.

PMID- 1348248
TI  - Mechanism of activation of liver glycogen synthase by swelling.
AB  - The mechanism linking the stimulation of liver glycogen synthesis to swelling
      induced either by amino acids or hypotonicity was studied in hepatocytes, in gel
      filtered liver extracts, and in purified preparations of particulate glycogen to
      which glycogen-metabolizing enzymes are bound. High concentrations of KCl, but
      not of potassium glutamate, were found to inhibit glycogen synthesis in
      permeabilized hepatocytes. Similarly, physiological concentrations (30-50 mM) of
      Cl- ions were also found to inhibit synthase phosphatase in vitro, whereas 10-20
      mM Cl- ions, a concentration found in swollen hepatocytes, did not inhibit
      synthase phosphatase. Synthase phosphatase activity was more sensitive to
      inhibition by Cl- ions at low (0.1%) than at high (1%) concentrations of
      glycogen. By contrast, 10 mM glutamate and aspartate, a concentration observed in
      hepatocytes incubated with glutamine or proline, stimulated synthase phosphatase
      in vitro. Therefore, it is proposed that the fall in intracellular Cl-
      concentration as well as the increase in intracellular glutamate and aspartate
      concentrations, that are observed in swollen hepatocytes in the presence of amino
      acids, are responsible, at least in part, for the stimulation of synthase
      phosphatase and, hence, of glycogen synthesis.

PMID- 1348249
TI  - Roles of TATA and initiator elements in determining the start site location and
      direction of RNA polymerase II transcription.

PMID- 1348250
TI  - Concentration-dependent regulation of neuronal gene expression by nerve growth
      factor.
AB  - NGF is a neurotrophic protein that promotes the survival, growth, and
      differentiation of developing sympathetic neurons. To directly determine the
      effects of different concentrations of NGF on neuronal gene expression, we
      examined mRNAs encoding the p75 low-affinity NGF (LNGF) receptor, T alpha 1 alpha
      tubulin (T alpha 1), and tyrosine hydroxylase (TH) in pure cultures of rat
      sympathetic neurons from postnatal day 1 superior cervical ganglia. Studies of
      the timecourse of gene expression during 2 wk in culture indicated that a 5-d
      incubation period would be optimal for the concentration-effect studies. Analysis
      of RNA isolated from neurons cultured in 2-200 ng/ml 2.5S NGF for 5 d revealed
      that, as the NGF concentration increased, neurons expressed correspondingly
      increased levels of all three mRNAs. Both LNGF receptor and TH mRNAs increased
      seven-fold, and T alpha 1 mRNA increased four-fold in neurons cultured in 200
      versus 10 ng/ml NGF. In contrast, T26 alpha-tubulin mRNA, which is constitutively
      expressed, did not alter as a function of NGF concentration. When neurons were
      initially cultured in 10 ng/ml NGF for 5 d, and then 200 ng/ml NGF was added,
      LNGF receptor, T alpha 1, and TH mRNAs all increased within 48 h. The timecourse
      of induction differed: T alpha 1 mRNA was maximal by 5 h, whereas LNGF receptor
      and TH mRNAs first began to increase at 12 h after the NGF increase. These
      experiments show that NGF regulates expression of a subset of mRNAs important to
      neuronal growth and differentiation over a broad concentration range, suggesting
      that the effects of NGF may be mediated by more than just a single receptor
      operating at one fixed affinity. These results also suggest a mechanism for
      coupling neuronal synthesis of axonal proteins to increases in size of the
      innervated target territory during growth of the organism.

PMID- 1348252
TI  - A novel microtubule-binding motif identified in a high molecular weight
      microtubule-associated protein from Trypanosoma brucei.
AB  - The major component of the cytoskeleton of the parasitic hemoflagellate
      Trypanosoma brucei is a membrane skeleton which consists of a single layer of
      tightly spaced microtubules. This array encloses the entire cell body, and it is
      apposed to, and connected with, the overlying cell membrane. The microtubules of
      this array contain numerous microtubule-associated proteins. Prominent among
      those is a family of high molecular weight, repetitive proteins which consist to
      a large extent of tandemly arranged 38-amino acid repeat units. The binding of
      one of these proteins, MARP-1, to microtubules has now been characterized in
      vitro and in vivo. MARP-1 binds to microtubules via tubulin domains other than
      the COOH-termini used by microtubule-associated proteins from mammalian brain,
      e.g., MAP2 or Tau. In vitro binding assays using recombinant protein, as well as
      transfection of mammalian cell lines, have established that the repetitive 38
      amino acid repeat units represent a novel microtubule-binding motif. This motif
      is very similar in length to those of the mammalian microtubule-associated
      proteins Tau, MAP2, and MAP-U, but both its sequence and charge are different.
      The observation that the microtubule-binding motifs both of the neural and the
      trypanosomal proteins are of similar length may reflect the fact that both
      mediate binding to the same repetitive surface, the microtubule, while their
      sequence and charge differences are in agreement with the observation that they
      interact with different domains of the tubulins.

PMID- 1348251
TI  - Intracellular cyclic AMP not calcium, determines the direction of vesicle
      movement in melanophores: direct measurement by fluorescence ratio imaging.
AB  - Intracellular movement of vesiculated pigment granules in angelfish melanophores
      is regulated by a signalling pathway that triggers kinesin and dyneinlike
      microtubule motor proteins. We have tested the relative importance of
      intracellular Ca2+ ([Ca2+]i) vs cAMP ([cAMP]i) in the control of such motility by
      adrenergic agonists, using fluorescence ratio imaging and many ways to
      artificially stimulate or suppress signals in these pathways. Fura-2 imaging
      reported a [Ca2+]i elevation accompanying pigment aggregation, but this increase
      was not essential since movement was not induced with the calcium ionophore,
      ionomycin, nor was movement blocked when the increases were suppressed by
      withdrawal of extracellular Ca2+ or loading of intracellular BAPTA. The
      phosphatase inhibitor, okadaic acid, blocked aggregation and induced dispersion
      at concentrations that suggested that the protein phosphatase PP-1 or PP-2A was
      continuously turning phosphate over during intracellular motility. cAMP was
      monitored dynamically in single living cells by microinjecting cAMP-dependent
      kinase in which the catalytic and regulatory subunits were labeled with
      fluorescein and rhodamine respectively (Adams et al., 1991. Nature (Lond.).
      349:694-697). Ratio imaging of F1CRhR showed that the alpha 2-adrenergic receptor
      mediated aggregation was accompanied by a dose-dependent decrease in [cAMP]i. The
      decrease in [cAMP]i was both necessary and sufficient for aggregation, since cAMP
      analogs or microinjected free catalytic subunit of A kinase-blocked aggregation
      or caused dispersal, whereas the cAMP antagonist RpcAMPs or the microinjection of
      the specific kinase inhibitor PKI5-24 amide induced aggregation. Our conclusion
      that cAMP, not calcium, controls bidirectional microtubule dependent motility in
      melanophores might be relevant to other instances of non-muscle cell motility.

PMID- 1348254
TI  - Predictive testing for multiple endocrine neoplasia type 1 using DNA
      polymorphisms.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited
      predisposition to neoplastic lesions of the parathyroids, pancreas, and the
      pituitary. We have previously located the predisposing genetic defect to the long
      arm of chromosome 11 by genetic linkage. In this study, 124 members of six MEN1
      families, including 59 affected individuals, were genotyped for restriction
      fragment length polymorphisms with different DNA probes, and the genetic linkage
      between these marker systems and MEN1 was determined. 13 marker systems (17 DNA
      probes) were found to be linked to MEN1. These markers are located within a
      region on chromosome 11 spanning 14% meiotic recombinations, with the MEN1 locus
      in the middle. Four of the marker systems are on the centromeric side of MEN1,
      and four on the telomeric side, based on meiotic crossovers. The remaining five
      DNA probes are closely linked to MEN1, with no crossovers in our set of families.
      The 13 marker systems can be used for an accurate and reliable premorbid test for
      MEN1. In most clinical situations it is possible to identify a haplotype of this
      part of chromosome 11 with the mutant MEN1 allele in the middle. The calculated
      predictive accuracy is greater than 99.5% if three such marker systems are
      informative. Therefore, genetic linkage testing can be used for informed genetic
      counseling in MEN1 families, and to avoid unnecessary biochemical screening
      programs.

PMID- 1348255
TI  - Determination of lymphocyte populations and subpopulations extracted from
      chronically inflamed human periodontal tissues.
AB  - The lymphocyte populations and subpopulations extracted from inflamed periodontal
      tissues of patients with adult periodontitis were determined. 34 patients were
      grouped according to the gingival index score (GI) of 1, 2 and 3. Gingival tissue
      from 2 involved teeth was excised, treated with collagenase, and infiltrating
      cells were isolated and identified using monoclonal antibodies for lymphocyte
      sets and subsets. The % of CD3+ cells was about 54.5% in all 3 patient groups,
      but the percentage of CD22+ cells increased from 28.9 +/- 3.3% in the group with
      GI = 1 to 33 +/- 1.2% in the group with GI = 3. %s of CD4+ cells and activated
      CD4+ cells increased from 30.2 +/- 2.1% and 4.7 +/- 1.7% in the group with GI = 1
      to 38.4 +/- 1.2% and 16.0 +/- 3.4% in the group with GI = 3, respectively, while
      in the same groups, the % of CD8+ cells decreased from 24.9 +/- 2.0% to 17.7 +/-
      1.6%. These data indicate a possible importance of activated CD4+ cells in
      pathogenetic mechanisms of periodontitis.

PMID- 1348253
TI  - Engraftment and long-term expression of human fetal hemopoietic stem cells in
      sheep following transplantation in utero.
AB  - Hemopoietic stem cells from human fetal liver were transplanted in utero into
      preimmune fetal sheep (48-54 days of gestation). The fate of donor cells was
      followed using karyotype analysis, by immunofluorescence labeling with anti-CD
      antibodies, and by fluorescent in situ hybridization using human-specific DNA
      probes. Engraftment occurred in 13 of 33 recipients. Of five live born sheep that
      exhibited chimerism, all expressed human cells in the marrow, whereas three
      expressed them in blood as well. Engraftment was multilineage (erythroid,
      myeloid, and lymphoid) and human hemopoietic progenitors (multipotent colony
      forming units, colony-forming units-granulocyte, macrophage, and erythroid burst
      forming units) capable of forming colonies in vitro were detected in all five
      lambs for greater than 2 yr. These progenitors responded to human-specific growth
      factors both in vitro and in vivo. Thus the administration of recombinant human
      IL-3 and granulocyte macrophage-colony-stimulating factor to chimeric sheep
      resulted in a 2.1-3.4-fold increase in the relative expression of donor (human)
      cells. These results demonstrate that the permissive environment of the preimmune
      fetal sheep provides suitable conditions for the engraftment and long-term
      multilineage expression of human hemopoietic stem cells in a large animal model.
      In this model, donor human cells appear to retain certain phenotypic and
      functional characteristics that can be used to manipulate the size of donor cell
      pool.

PMID- 1348257
TI  - The use of H2-receptor antagonists in the nursing home.

PMID- 1348256
TI  - Reducing the use of H2-receptor antagonists in the long-term-care setting.
AB  - OBJECTIVES: To examine the patterns of H2 blocker use in the long-term-care
      setting and to assess the effect of educational interventions designed to improve
      H2 blocker utilization patterns. DESIGN: Time-series quasi-experimental study and
      retrospective chart review. SETTING: A large academically-oriented long-term-care
      facility. PATIENTS: Institutionalized elderly patients with a mean age of 88
      years receiving H2 blocker therapy. INTERVENTIONS: Two interventions involving
      group discussions with the medical staff, supporting educational materials, and
      physician-specific listings of patients receiving H2 blockers were employed
      sequentially over a 32-month period. RESULTS: Each intervention resulted in
      substantial reductions in medication use (59.6% and 32.1%, respectively).
      Indications for H2 blocker use were determined retrospectively for patients
      identified as receiving therapy prior to the interventions (n = 110). Forty-one
      percent were found to be receiving therapy for reasons unsubstantiated by the
      medical literature. These patients were more likely to be discontinued from
      therapy than those receiving therapy for substantiated indications (P less than
      0.01), consistent with the primary focus of the educational interventions.
      CONCLUSIONS: These results suggest that the excessive use of H2 blocker therapy
      in the long-term care setting responds to educational interventions with
      therapeutically appropriate reductions in utilization. Repeated interventions are
      necessary to maintain such reductions over time although there may be some
      reduction in the effectiveness of the intervention with repetition.

PMID- 1348258
TI  - Acute colitis associated with prolonged administration of neuroleptics.
AB  - We describe a 29-year-old patient who developed acute colitis limited to the
      sigmoid and left colon with features mimicking ischemic injury after a prolonged
      administration of trifluoroperazine and levomepromazine, two phenothiazines in
      association with haloperidol, another neuroleptic, and biperidene, an
      anticholinergic compound. The discontinuation of these drugs was followed by a
      prompt and complete recovery, and no other cause of acute colitis was found. The
      subsequent administration of sultopride, a neuroleptic from the benzamide family
      and then the readministration of haloperidol were well tolerated. No colonic
      disorder occurred for the following months. This case strongly supports the view
      that neuroleptic agents, in particular phenothiazines, may induce acute colitis
      and that haloperidol, a butyrophenone derivative, or sultopride, a benzamide
      related neuroleptic, can be administered thereafter without recurrence of the
      disease.

PMID- 1348259
TI  - Sulfasalazine-induced fulminant hepatic failure.
AB  - We report two cases of massive hepatic necrosis associated with sulfasalazine.
      Both patients had underlying inflammatory bowel disease. One of the patients had
      a history of an ill-defined autoimmune disorder (Sjogren's syndrome). Symptoms
      and signs of a generalized hypersensitivity reaction were present in both
      patients. One patient died of a subarachnoid hemorrhage while awaiting
      transplant, the second died 2 weeks after transplant from disseminated
      aspergillosis. These two cases remind us of one of the potential hazards of
      sulfasalazine at a time when alternative therapies are now available.

PMID- 1348260
TI  - Genetic linkage analysis in hypertension: principles and practice.
AB  - BACKGROUND: Primary hypertension is a hereditary disorder characterized by a
      complex etiological interplay of multiple genetic and environmental factors,
      until now defying attempts at identifying pathogenetically important genes. The
      marriage of classical genetics and molecular techniques is now offering a
      powerful set of tools to uncover such disease-relevant genes. SUMMARY: Based upon
      the availability of methods to directly examine chromosomal and genomic DNA
      structures, molecular genetics has at its disposal today an array of markers far
      more numerous and specific than the phenotype parameters used in classical
      genetics. In addition, use of DNA polymorphisms takes the process of genetic
      analysis immediately to that level of investigation--the genome--from which
      relevant data will ultimately come forth. The deployment of these tools in the
      pursuit of elucidating the pathogenesis of hereditary hypertension, and their use
      for two commonly applied strategies, candidate gene analysis and reverse
      genetics, are discussed. SIGNIFICANCE: Whilst still in its early stages, the
      application of molecular genetic methods to the study of hereditary hypertension
      now holds the realistic promise of identifying disease-relevant genes. This will
      provide the basis for advanced diagnostic, preventive and therapeutic approaches.

PMID- 1348261
TI  - Impaired inotropic response to alpha 1- but not to beta-adrenoceptor stimulation
      in isolated hearts from spontaneously hypertensive rats.
AB  - OBJECTIVES: Hypertension in humans and experimental animals is known to be
      associated with an increase in left ventricular myocardial mass. The development
      of cardiac hypertrophy is not caused by increased blood pressure alone; the
      autonomic nervous system may also play an important role. DESIGN: The functional
      responses to the beta-adrenoceptor agonists isoprenaline, dobutamine, salbutamol
      and terbutaline, and the alpha 1-adrenoceptor agonists methoxamine, cirazoline
      and phenylephrine were studied in isolated (Langendorff) hearts from
      spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY)
      controls. The results were compared with data from radioligand binding
      experiments. RESULTS: There was no significant difference in the increase of left
      ventricular pressure induced by all beta-adrenoceptor agonists studied in SHR and
      WKY rat hearts. Although there was no significant difference in the response to
      phenylephrine, the inotropic responses to cirazoline and methoxamine proved to be
      significantly weaker in hearts from SHR than in those from WKY rats. Binding
      experiments with 3H-prazosin revealed no differences in density or affinity for
      cardiac tissues from SHR and WKY rats. CONCLUSIONS: Long-standing hypertension
      leads to an impaired response of the isolated heart to alpha 1-adrenoceptor
      stimulation, without changes in alpha 1-receptor density or affinity. It seems
      likely that changes in postreceptor events are responsible for the impaired
      inotropic response to alpha 1-adrenoceptor agonists in hearts from SHR.

PMID- 1348262
TI  - [Signal transduction in cells].

PMID- 1348263
TI  - [Progress on diagnosis and therapy of kidney diseases complicated with
      periarteritis nodosa and the related diseases].

PMID- 1348264
TI  - [Progress on diagnosis and therapy of diabetic nephropathy].

PMID- 1348265
TI  - [Kidney diseases associated with virus infections].

PMID- 1348266
TI  - Outpatient management of patients infected with human immunodeficiency virus.
AB  - The outpatient management of patients infected with human immunodeficiency
      syndrome is reviewed. Patients with CD4+ cell counts of greater than 0.5 x
      10(9)/L (500/mm3) require no specific intervention except vaccination against
      influenza, pneumococcus, and possibly hepatitis B. They should have a follow-up
      examination every 3 to 6 months. Because of its success in preventing the
      progression of the disease, zidovudine (AZT), 100 mg five times per day, is
      recommended for patients with CD4+ cell counts of less than 0.5 x 10(9)/L
      (500/mm3). During this stage of the disease, a patient should be seen every 1 to
      3 months and monitored for drug toxicity and disease progression. Patients with
      CD4+ counts of less than 0.2 x 10(9)/L (200/mm3) are at high risk of developing
      Pneumocystis carinii pneumonia. Prophylaxis with oral trimethoprim
      sulfamethoxazole (one double-strength tablet three times weekly) or dapsone (100
      mg three times weekly) is recommended. Treatment costs for the patient with CD4+
      cells less than 0.5 x 10(9)/L (500/mm3) are at least $3000 per year.

PMID- 1348267
TI  - IS902, an insertion element of the chronic-enteritis-causing Mycobacterium avium
      subsp. silvaticum.
AB  - An insertion sequence element of Mycobacterium avium subsp. silvaticum was
      isolated and its complete nucleotide sequence determined. IS902 is 1470 bp in
      size and is repeated 10-12 times per genome. An open reading frame of 1200 bp was
      identified, encoding a protein product of Mr 43932. This protein is highly
      similar to the predicted proteins of IS900 of Mycobacterium paratuberculosis,
      IS116 of Streptomyces clavuligerus and IS110 of Streptomyces coelicolor. IS902
      lacks terminal inverted repeats and flanking direct repeats but displays
      insertion site specificity.

PMID- 1348268
TI  - Cloning of dapD, aroD and asd of Leptospira interrogans serovar
      icterohaemorrhagiae, and nucleotide sequence of the asd gene.
AB  - Metabolites such as diaminopimelate and some aromatic derivatives, not
      synthesized in mammalian cells, are essential for growth of bacteria. As a first
      step towards the design of a new human live vaccine that uses attenuated strains
      of Leptospira interrogans, the asd, aroD and dapD genes, encoding aspartate beta
      semialdehyde dehydrogenase, 3-dehydroquinase and tetrahydrodipicolinate N
      succinyltransferase, respectively, were cloned by complementation of Escherichia
      coli mutants. The complete nucleotide sequence of the asd gene was determined and
      found to contain an open reading frame capable of encoding a protein of 349 amino
      acids with a calculated Mr of 38,007. Comparison of this deduced L. interrogans
      aspartate beta-semialdehyde dehydrogenase amino acid sequence with those of the
      same enzyme from Saccharomyces cerevisiae and Corynebacterium glutamicum revealed
      46% and 36% identity, respectively. By contrast, the identity between the L.
      interrogans enzyme and the Streptococcus mutans or E. coli enzymes was less than
      31%. Highly conserved sequences within aspartate semialdehyde dehydrogenase from
      the five organisms were observed at the amino and carboxyl termini, and around
      the cysteine of the active site.

PMID- 1348269
TI  - The concept of supersensitivity psychosis.
AB  - The hypothesis that chronic neuroleptic treatment may induce relapse in some
      schizophrenic patients has received considerable attention. This effect, usually
      called supersensitivity psychosis, has been attributed to neuroleptic-induced
      changes in mesolimbic or mesocortical dopaminergic receptors. However, research
      has not established that neuroleptics cause the proposed effect, and
      considerations of mechanism have not been separated from those of causation. The
      focus of research in this area should be the establishment or refutation of a
      causal relationship between chronic neuroleptic use and psychotic relapse.

PMID- 1348270
TI  - The microphysiology of peripheral taste organs.
AB  - Recent studies on how peripheral taste organs function have revealed a number of
      intriguing membrane mechanisms underlying taste transduction. The story is still
      evolving, but certain generalities can now be stated confidently. For example,
      there is no one single chemosensory membrane transduction event. Instead, the
      different taste qualities--sweet, sour, salty, bitter--are subserved by different
      mechanisms. Furthermore, chemical and electrical synaptic processing in the taste
      bud is likely to modulate the output of the taste organs and may contribute to
      how different taste qualities are discriminated. Synapses occur between adjacent
      cells in the taste organ as well as between receptor cells and sensory fibers.
      The preponderance of data indicates that biogenic amines are present in taste
      buds and exert some form of neuromodulatory control, if not frank
      neurotransmission, in peripheral taste organs. Current research in the
      microphysiology of taste buds includes extending and refining our understanding
      of how the apical, chemosensitive regions of receptor cells respond to taste
      stimuli, identifying what synaptic transmitters exist in taste organs, and
      exploring synaptic mechanisms in taste buds.

PMID- 1348271
TI  - Dual ultrastructural localization of enkephalin and tyrosine hydroxylase
      immunoreactivity in the rat ventral tegmental area: multiple substrates for
      opiate-dopamine interactions.
AB  - Endogenous opiates modulate activity in the mesocorticolimbic dopaminergic
      system, and this interaction is thought to underlie major aspects of motoric,
      reward-seeking, and stress-coping behaviors. We sought to determine the
      ultrastructural substrate for this modulatory action at the level of dopaminergic
      perikarya in the rat ventral tegmental area (VTA). Using a dual-labeling,
      immunoperoxidase and immunogold-silver method, we localized antisera directed
      against leu5-enkephalin (ENK) and the catecholamine-synthesizing enzyme tyrosine
      hydroxylase (TH) in acrolein-fixed sections through the VTA. ENK-like
      immunoreactivity (ENK-LI) was visualized within unmyelinated axons and in axon
      terminals. In terminals, ENK-LI was densely localized to one or more dense-cored
      vesicles and either densely or lightly detected surrounding small clear vesicles.
      Immunoreactive dense-cored vesicles were occasionally associated with the
      presynaptic specialization but were more frequently detected at distant sites
      along the plasmalemmal surface, often in apposition to astrocytic processes. ENK
      immunoreactive terminals formed both symmetric and asymmetric synapses, most
      frequently on large proximal dendrites. Direct appositions without glial
      separation were also detected between terminals containing ENK-LI and other ENK
      labeled or unlabeled terminals. In contrast to ENK-LI, immunolabeling for TH was
      primarily detected within perikarya and dendrites in the VTA. Of the ENK
      immunoreactive terminals that formed synaptic contacts in single sections,
      approximately 50-60% were in association with TH-labeled dendrites. The remainder
      formed synapses on dendrites lacking detectable immunoreactivity for TH. Multiple
      ENK-immunoreactive terminals occasionally formed convergent synaptic contacts on
      single TH-labeled or unlabeled dendrites. Furthermore, individual ENK-labeled
      terminals sometimes formed divergent contacts on two TH-labeled or unlabeled
      dendrites. When a single ENK-immunoreactive terminal made dual synaptic contacts
      on TH-labeled dendrites, the latter were usually in close apposition to one
      another. These findings represent the first ultrastructural demonstration that
      opioid peptide-containing terminals provide a direct synaptic input to
      dopaminergic, as well as nondopaminergic, neurons in the VTA. In addition, the
      morphological evidence suggests that endogenous opioid peptides (1) may be
      released from nonsynaptic sites, (2) may modulate the release of transmitters
      from other terminals, and/or (3) may synchronize the activity of multiple
      neuronal targets in the VTA. These results provide a number of morphological
      substrates through which opiates may directly or indirectly regulate activity in
      mesocorticolimbic dopaminergic pathways.

PMID- 1348272
TI  - Does lineage determine the dopamine phenotype in the tadpole hypothalamus?: A
      quantitative analysis.
AB  - The ancestry of dopaminergic (DA) neurons in the Xenopus laevis hypothalamus was
      investigated by combining intracellular lineage dye injections of 16- and 32-cell
      blastomeres with the immunofluorescent detection of tyrosine hydroxylase at
      tadpole stages. At these stages, DA neurons in the hypothalamus comprise a
      discrete nucleus that contains from 22 to 45 cells on each side [mean = 32.6 +/-
      6.6 (SD)]. The DA nucleus descends from only four of the 16-cell blastomeres. The
      two dorsal midline blastomeres (D1.1) are the major progenitors, and in all
      embryos studied they contributed to the DA nucleus. The two dorsal lateral
      blastomeres (D1.2) contribute to the DA nucleus in only about half of the
      embryos. Thus, the DA nucleus descends only from a discrete group of progenitors,
      and the participation of some of the progenitors in the DA lineage is only
      probabilistic. The number of DA neurons generated by the same blastomere varied
      greatly in different animals. This variation in cell number correlated with the
      degree of coherence and the density of the clone in the hypothalamus, rather than
      with clonal ancestry. Bilateral deletion of the major 32-cell progenitor (D1.1.1)
      resulted in a nearly complete restitution of the DA nucleus in 74% of the embryos
      that successfully completed gastrulation and neurulation. In the rest, the
      hypothalamus was smaller than normal or missing, and the DA nucleus was
      significantly reduced in size or absent. These results show that the DA nucleus
      can be restored after its normal lineage is deleted, but complete regulation is
      not always accomplished. Several blastomere progenitors dramatically altered
      their contribution to the DA nucleus after D1.1.1 ablation, including two
      blastomeres that normally do not contribute to the DA lineage. Thus, the fate to
      produce DA neurons is not determined at cleavage stages.

PMID- 1348275
TI  - Impact of the new biologies on the medical and pharmaceutical sciences. British
      Pharmaceutical Conference 1991. Merseyside, September 10-13, 1991.

PMID- 1348273
TI  - 2-Chloroadenosine potentiates the alpha 1-adrenergic activation of phospholipase
      C through a mechanism involving arachidonic acid and glutamate in striatal
      astrocytes.
AB  - In cultured striatal astrocytes, 2-chloroadenosine, an adenosine analog resistant
      to adenosine deaminase, although inactive alone, markedly potentiated the
      activation of phospholipase C induced by methoxamine, an alpha 1-adrenergic
      agonist. This effect was suppressed by antagonists of either A1 adenosine or
      alpha 1-adrenergic receptors. An influx of calcium and two distinct G-proteins
      are involved in this phenomenon since the potentiating effect of 2-chloradenosine
      was suppressed in the absence of external calcium or when cells were pretreated
      with pertussis toxin. In addition, arachidonic acid is likely involved in this
      potentiating effect. This was shown first by examining the effects of inhibitors
      of phospholipase A2 or arachidonic metabolism, then by examining the action of
      arachidonic acid on the production of inositol phosphates in either the presence
      or absence of methoxamine, and finally by measuring the release of arachidonic
      acid. The sequential activation of phospholipase C and of protein kinase C is
      required for the 2-chloroadenosine-induced activation of phospholipase A2 since 2
      chloroadenosine markedly stimulated phospholipase C activity in the absence of
      methoxamine when protein kinase C was activated by a diacylglycerol analog.
      Finally, the enhancing effect of 2-chloroadenosine on the methoxamine-evoked
      response seems to result from an inhibition of glutamate reuptake into astrocytes
      by arachidonic acid. Indeed, the potentiating effect of 2-chloroadenosine was
      suppressed when external glutamate was removed enzymatically and mimicked by
      either selective inhibitors of the glutamate reuptake process or direct
      application of glutamate.

PMID- 1348274
TI  - Mesencephalic dopaminergic neurons in primary cultures express functional
      neurotensin receptors.
AB  - The cellular distribution and functional aspects of neurotensin (NT) binding
      sites in rat mesencephalic cells in primary culture were investigated by an
      original approach combining anatomical and biochemical studies. Using a double
      labeling protocol combining 125I-NT receptor radioautography and tyrosine
      hydroxylase (TH) immunocytochemistry, we obtained the first direct visualization
      of NT binding sites on TH-immunoreactive neurons. Eighty percent of the TH
      neurons were endowed with NT binding sites, which can be observed on both cell
      bodies and processes. TH-immunoreactive neurons were characterized as
      dopaminergic neurons by their ability to take up dopamine in a benztropine- and
      nomifensine-sensitive manner. In the mesencephalic cultures, NT increased
      potassium-evoked release of tritiated dopamine, and the relative potencies of
      various NT-related peptides to increase dopamine release were in good agreement
      with their abilities to bind to NT sites. These results show for the first time
      that cultured rat mesencephalic dopaminergic cells express functional NT
      receptors. Finally, the specificity and distribution of NT receptors on
      dopaminergic neurons in primary culture are quite similar to what was observed in
      the adult rat brain using pharmacological and radioautographic approaches. These
      data indicate that NT can influence the activity of dopaminergic neurons at very
      early stages of the rat brain development.

PMID- 1348276
TI  - Impact of the new biologies on the medical and pharmaceutical sciences.

PMID- 1348278
TI  - Gene therapy of cystic fibrosis lung disease.

PMID- 1348277
TI  - Pathogenesis of AIDS.

PMID- 1348279
TI  - From proteins to protein interacting drugs.

PMID- 1348280
TI  - Pharmaceutics of protein drugs.

PMID- 1348281
TI  - Delivery systems for biopharmaceuticals.

PMID- 1348282
TI  - New biotechnologies: challenges for the regulatory authorities.

PMID- 1348283
TI  - Clinical pharmacology of recombinant proteins.

PMID- 1348284
TI  - The human genome project. Purpose and potential.

PMID- 1348287
TI  - North American Conference on Cancer in Hispanics.

PMID- 1348288
TI  - International consensus report urges sweeping reform in asthma treatment.

PMID- 1348286
TI  - Expression of the CD54 (ICAM-1) and CD11a (LFA-1) adhesion molecules in oral
      mucosal inflammation.
AB  - Previous studies of chronic dermatoses have suggested that expression of the CD54
      cell surface antigen (intercellular adhesion molecule-1, ICAM-1) by keratinocytes
      is a feature of chronic inflammation. However, whether such expression is a
      prerequisite for intraepithelial migration of lymphocytes is unclear. The present
      study evaluated the expression of CD54 and its ligand, CD11a (lymphocyte function
      associated antigen, LFA-1) in oral lesions of lichen planus, recurrent aphthous
      stomatitis, secondary Sjogren's syndrome and traumatic ulceration using an
      immunoperoxide technique. In 33 of 56 lesions examined, substantial numbers of
      CD11a + cells were present within oral mucosal epithelium despite an absence of
      detectable keratinocyte CD54 antigen expression. Consequently, CD54/CD11a
      adhesion interactions may not be critical in the initiation of oral mucosal
      inflammation.

PMID- 1348290
TI  - [The 65th Congress of the Japanese Society for Bacteriology. March 31-April 2,
      1992. Morioka, Japan. Abstracts].

PMID- 1348291
TI  - [The 78th Congress of the Japanese Society of Gastroenterology. April 8-10, 1992,
      Tokyo, Japan. Abstracts].

PMID- 1348289
TI  - Hepatic and gastrointestinal effects in an occupational cohort exposed to 2,3,7,8
      tetrachlorodibenzo-para-dioxin.
AB  - OBJECTIVE: To examine the effect of occupational exposure to substances
      contaminated with 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) on the liver and
      gastrointestinal system. DESIGN: A medical survey. PARTICIPANTS: The exposed
      participants were employed at two chemical plants more than 15 years earlier in
      the manufacture of sodium trichlorophenol and its derivatives. The reference
      group consisted of individuals with no occupational exposure to phenoxy
      herbicides and who lived within the communities of the workers. A total of 281
      workers and 260 unexposed referents participated in the medical study.
      MEASUREMENTS AND MAIN RESULTS: The workers had substantial exposure to substances
      contaminated with TCDD, as evidenced by a mean serum TCDD level, lipid adjusted,
      of 220 pg per gram of lipid compared with a mean of 7 pg per gram of lipid in the
      referents. Compared with the unexposed reference group, workers had a
      statistically significantly elevated risk for an out-of-range gamma
      glutamyltransferase (GGT) level (odds ratio, 2.27; 95% confidence interval, 1.17
      to 4.39 [unadjusted for confounders]). In multivariate analyses run with logistic
      regression, a statistically significant interaction was found between TCDD
      exposure and lifetime alcohol consumption, indicating that the elevated risk for
      an out-of-range GGT was confined to those workers with a history of alcohol
      consumption and that the risk among the alcohol-consuming workers for an out-of
      range GGT increased with increasing TCDD level. No difference was found between
      workers and referents for any of the other liver and gastrointestinal outcomes of
      interest. CONCLUSIONS: This study found no evidence of an elevated risk for
      clinical hepatic or gastrointestinal disease in a group of workers with high
      exposure to TCDD. However, TCDD-exposed workers with a history of sufficient
      alcohol consumption were found to have a statistically significantly elevated
      risk for an out-of-range GGT compared with referents.

PMID- 1348292
TI  - [Pheochromocytoma--basic and clinical analyses].
AB  - A variety of vasoactive substances including biogenic amines, neuropeptide Y,
      somatostatin, enkephalin, ACTH, corticotropin-releasing hormone, growth hormone
      releasing hormone, vasoactive intestinal peptide, calcitonin, and atrial
      natriuretic factor have been extracted from intra-adrenal and extra-adrenal
      pheochromocytomas in men. Some of them appear to play an important role for the
      development of hypertension or clinical serious symptoms. However, informations
      on the molecular forms of other substances in pheochromocytomas are still
      limited, and precise amount of the peptides or hormones in the tumors has not yet
      been quantitated. Numerous in vitro or in vivo studies of this documented
      neoplasm over the years have been reviewed in this manuscript. Clinical analyses
      of early diagnosis, localization diagnosis, treatment of multiple endocrine
      neoplasia, preoperative and operative treatments are also evaluated in this
      paper. These informations will probably provide additional evidence for the multi
      secretory APUD cells of neural crest origin and will contribute the therapy in
      patients with pheochromocytoma.

PMID- 1348293
TI  - Clinicopathological significance of c-erbB-2 protein expression in human gastric
      carcinoma.
AB  - One hundred seventy-nine primary human gastric tumors not associated with early
      cancer or noncurative resection were examined immunohistochemically for the
      expression of c-erbB-2 protein. Positive staining, regarded as an indication of
      gene amplification, was evident in 22(12%) of the tumors. Of various
      clinicopathological factors considered, a statistically significant difference in
      association with frequency of expression was noted only for histological
      differentiation, as follows: 39% positive staining in papillary, 17% in well
      differentiated, 5% in moderately differentiated, and 4% in undifferentiated
      adenocarcinomas (P greater than 0.01). The 5-year survival rates of patients with
      positive and negative c-erbB-2 staining were 57% and 59%, respectively. These
      findings indicate that, in the case of human gastric adenocarcinoma, expression
      of c-erbB-2 protein is correlated with tumor histological differentiation. Our
      results also suggest that the presence or absence of c-erbB-2 protein may not
      serve as a prognostic indicator, particularly in cases of adenocarcinoma of the
      stomach.

PMID- 1348294
TI  - Non-icteric pancreas head carcinoma fares worse than icteric pancreas head
      carcinoma.
AB  - A total of 22 patients with non-icteric pancreas head carcinoma were
      retrospectively compared with 61 patients with icteric pancreas head carcinoma.
      No significant difference was found regarding age, sex, greatest diameter,
      macroscopic type, microscopic type, stage, lymphatic permeation, perineural
      infiltration, venous invasion, lymph node metastasis, and the presence of cancer
      cells at the surgical margins. The main location of pancreas head carcinoma could
      be divided into two sites: the superior (pericholedochal), and inferior or distal
      (excholedochal) areas of the pancreas head. Sixteen (73%) of the 22 non-icteric
      pancreas head carcinomas were located in the inferior or distal area
      (excholedochal), while 28 (46%) of the 61 icteric pancreas head carcinomas were
      situated in the superior portion (pericholedochal) (P less than 0.05). One (5%)
      of the 22 non-icteric pancreas head carcinomas was small pancreas carcinoma,
      compared with 11 (18%) of the 61 icteric pancreas head carcinomas. The cumulative
      2-year and 4-year survival rates of the 22 patients with non-icteric pancreas
      head carcinoma were significantly worse than those of the 61 patients with
      icteric pancreas head carcinoma [7.9% vs. 24.6% (P less than 0.05) and 0% vs.
      13.4% (P less than 0.01)]. These findings suggest that non-icteric pancreas head
      carcinomas normally arise in an area far from the biliary tree, and include a
      greater number of large tumors. Any resulting difficulty and delay in the
      diagnosis and treatment of this disease will usually lead to a worsening of the
      clinical course of non-icteric pancreas head carcinoma.

PMID- 1348295
TI  - Autoantibody against oxidised LDL and progression of carotid atherosclerosis.
AB  - Oxidative modification of LDL renders it immunogenic and autoantibodies to
      epitopes of oxidised LDL, such as malondialdehyde (MDA)-lysine, are found in
      serum and recognise material in atheromatous tissue. However, there has been no
      prospective study to assess the importance of oxidised LDL among patients with
      vascular disease. We compared the titre of autoantibodies to MDA-modified LDL and
      native LDL in baseline serum samples of 30 eastern Finnish men with accelerated
      two-year progression of carotid atherosclerosis and 30 age-matched controls
      without progression. Neither group had specific antibody binding to native LDL. A
      titre was defined as a ratio of antibody binding to MDA-LDL/binding to native
      LDL. Cases had a significantly higher titre to MDA-LDL (2.67 vs 2.06, p = 0.003).
      Cases also had a greater proportion of smokers (37% vs 3%), higher LDL
      cholesterol (4.2 mmol/l vs 3.6 mmol/l), and higher serum copper concentration
      (1.14 mg/l vs 1.04 mg/l). Even after adjusting for these variables and the
      severity of baseline atherosclerosis, the difference in antibody titre remained
      significant in a multifactorial logistic model (p = 0.031). Thus, the titre of
      autoantibodies to MDA-LDL was an independent predictor of the progression of
      carotid atherosclerosis in these Finnish men. Our data provide further support
      for a role of oxidatively modified LDL in atherogenesis.

PMID- 1348296
TI  - 5-alpha-reductase activity and risk of prostate cancer among Japanese and US
      white and black males.
AB  - The incidence of prostate cancer varies widely between countries and ethnic
      groups. Black-Americans have the highest incidence rates world wide, whereas
      native Japanese have among the lowest. The reasons for this risk differential are
      unknown, although we have previously shown that higher circulating testosterone
      concentrations in young adult black men compared with young adult white men may
      explain the underlying differences in subsequent prostate cancer incidence
      between these two populations. We have now compared serum testosterone
      concentrations in young adult Japanese men with those of young adult whites and
      blacks, but found no significant differences. However, these white and black men
      had significantly higher values of 3 alpha, 17 beta androstanediol glucuronide
      (31% and 25% higher, respectively) and androsterone glucuronide (50% and 41%
      higher, respectively) than Japanese subjects. These two androgens are indices of
      5 alpha-reductase activity. Our results raise the possibility that reduced 5
      alpha-reductase activity has a role in producing the low prostate cancer
      incidence rates among Japanese. This finding may have important implications for
      prostate cancer prevention.

PMID- 1348297
TI  - Genetic diagnosis of Gaucher's disease.
AB  - The inherited disorder Gaucher's disease can be caused by various mutations in
      the glucocerebrosidase gene. Some mutations may be associated with greater
      severity, and there is a need for methods of gene analysis that would facilitate
      screening and diagnosis. We have studied the molecular basis of Gaucher's disease
      in twelve unrelated patients of diverse ethnic origin by means of the
      amplification refractory mutation system (ARMS). Primers for the polymerase chain
      reaction were designed to discriminate between mutant and wild-type alleles of
      glucocerebrosidase and to allow separation from products of the related
      pseudogene. The nucleotide 1226 mutation (asparagine 370----serine) and 84GG (an
      insertional frameshift mutation) were found exclusively in five patients of
      Ashkenazi Jewish descent (7 and 2 of the 10 disease alleles, respectively). Two
      point mutations, at nucleotides 1448 (leucine 444----proline) and 1504 (arginine
      463----cysteine), were found in 4 and 3 alleles, respectively; they were
      associated with rapidly progressive disease and neurological involvement in non
      Jewish patients. The ARMS procedure for direct detection of common mutations in
      glucocerebrosidase will facilitate genetic counselling and screening programmes
      for individuals at risk of Gaucher's disease.

PMID- 1348298
TI  - Diagnostic value of decreasing IgG, IgA, and IgM antibody titres after
      eradication of Helicobacter pylori.
AB  - Titres of antibody to Helicobacter pylori are known to fall with eradication of
      bacteria. To find out what degree of fall would reliably indicate eradication,
      144 patients with Helicobacter pylori infection were given antimicrobial therapy
      for 2 weeks and then followed up at 6 weeks, 6 months, and 12 months with
      serological tests, bacterial cultures, and histological studies of gastric
      specimens. 6 weeks after treatment IgG titres had fallen by 20-30% irrespective
      of the success of bacterial eradication. In the 121 bacteria-negative patients
      the decrease continued. 6 and 12 months after treatment the titre was 50% or less
      of pretreatment value in 97% of these patients. In the 23 patients who remained
      infected, the initial drop of IgG titres, if any, was followed by unchanged or
      slightly rising titres. IgA and IgM titres, initially raised in 64% and 4% of the
      patients, respectively, showed similar trends. The high sensitivity (97%) of the
      IgG antibody tests and a consistent fall within 6 months after eradication of H
      pylori infection made IgG the most useful immunoglobulin class for follow-up of
      antimicrobial therapy in individual patients. IgA antibodies were valuable in the
      2% patients who had raised titres in this immunoglobulin class only. The few
      patients (5.5%) who had raised IgM titres also had high IgG titres. Serological
      tests thus are a cheap and reliable means of monitoring success of eradication of
      H pylori.

PMID- 1348299
TI  - Childhood living conditions and Helicobacter pylori seropositivity in adult life.
AB  - Infection with Helicobacter pylori increases an individual's risk of peptic
      ulceration and gastric cancer. In the developed world, prevalence of infection
      rises with age and varies with social class. We used a cross-sectional study
      design to test the hypothesis that H pylori infection would be more closely
      associated with childhood living conditions than with current socioeconomic
      status. Prevalence of IgG antibodies against H pylori was determined with an
      enzyme-linked immunosorbent assay in 215 subjects (median age 46 years, range 18
      82) attending a health-screening clinic in London. Seropositivity varied from 9%
      (age less than 30) to 67% (greater than or equal to 70). Subjects were asked
      about their living conditions at present and when they were aged 8 years. Absence
      of a fixed hot-water supply (p = 0.0005) and domestic crowding (p = 0.0005) in
      childhood were powerful independent risk factors for current infection with H
      pylori. Among current living conditions, only the number of children living in
      the household was independently associated with H pylori infection (p = 0.004).
      Most British adults infected with H pylori probably became infected by household
      contact in childhood.

PMID- 1348300
TI  - Physical manoeuvres for combating orthostatic dizziness in autonomic failure.
AB  - Some patients with orthostatic hypotension combat orthostatic dizziness by leg
      crossing and squatting. Changes in blood pressure with these manoeuvres were
      studied in 7 patients with hypoadrenergic orthostatic hypotension and in 6
      healthy subjects. Without leg-crossing, 5 of the patients reported dizziness
      within 10 min of standing up. Crossing of the legs allowed all to stand for 10
      min or more, and there was an associated increase in mean blood pressure of 13
      (SD 6) mm Hg compared with 1 (4) in healthy controls; the corresponding figures
      for squatting were 44 (18) and 8 (6) mm Hg. Patients with orthostatic intolerance
      should be told about these blood-pressure-raising manoeuvres.

PMID- 1348301
TI  - Antibodies to oxidised LDL in atherosclerosis.

PMID- 1348302
TI  - Amputation or arterial reconstruction?

PMID- 1348303
TI  - Cancer screening and prevention: organ vs non-organ specific?

PMID- 1348304
TI  - Orderly bone transport.

PMID- 1348305
TI  - Clinical management of trisomy 18.

PMID- 1348306
TI  - Incidence of childhood-onset insulin-dependent diabetes mellitus: the EURODIAB
      ACE Study.
AB  - EURODIAB ACE is a collaborative European study that was set up to assess
      incidence of childhood insulin-dependent diabetes mellitus (IDDM) in Europe, test
      the proposal of a south-north gradient, and to gather information to determine
      the causes and pathogenesis of the disease. Here, the basic epidemiological
      results are reported. Newly diagnosed cases of IDDM in children aged up to 15
      years were identified prospectively in twenty-four geographically well-defined
      study regions in Europe and Israel (a total of 16.8 million children) during 1989
      and 1990. 3060 cases were identified with estimated ascertainment rates exceeding
      90% in all study regions. Age-standardised and sex-standardised incidence rates
      varied widely, ranging from 4.6 (northern Greece) to 42.9 (two regions in
      Finland) cases per 100,000 per year. Rates in southern Europe were generally
      higher than previously assumed, and there was an unexpectedly high incidence in
      Sardinia, which had the second highest rate (30.2 cases per 100,000 per year)
      recorded in Europe. Eastern European regions had generally low rates. The
      collaborative network now established provides a framework for further studies to
      examine the complex interaction between genetic and environmental factors in the
      cause and pathogenesis of IDDM.

PMID- 1348307
TI  - Glutathione deficiency and human immunodeficiency virus infection.

PMID- 1348308
TI  - Avoidance of emergency surgery in newborn infants with trisomy 18.
AB  - Trisomy 18 (Edwards' syndrome) presents with characteristic external features as
      well as life-threatening abnormalities; many of these abnormalities require
      surgical correction during the neonatal period. Children with trisomy 18 have a
      very short life expectancy, and all long-term survivors have severe mental
      retardation. Difficult medical and ethical issues arise over whether or not to
      institute treatment when a newborn infant with suspected trisomy 18 has a life
      threatening anomaly. We studied the policy of treatment in seven patients with
      clinical Edwards' syndrome. For three, the period of uncertainty was shortened
      because trisomy 18 was rapidly diagnosed by karyotyping of a bone-marrow
      aspirate. Four of the patients underwent surgery before the diagnosis of trisomy
      18 was confirmed by routine karyotyping in lymphocytes; karyotyping in bone
      marrow might have allowed invasive treatment to be avoided in three of these.
      Rapid confirmation of clinically suspected Edwards' syndrome is very important
      because surgery may then be withheld. A newborn infant with trisomy 18 should be
      considered as a patient with a hopeless outlook who ought not to be subjected to
      invasive procedures. The decision to withdraw or withhold treatment should be
      discussed frankly with the parents. The period of uncertainty can be reduced to a
      minimum by the use of karyotyping in bone marrow.

PMID- 1348309
TI  - Time to abandon TNM staging of breast cancer?

PMID- 1348310
TI  - Breastfeeding and intelligence.

PMID- 1348311
TI  - Breastfeeding and intelligence.

PMID- 1348312
TI  - Breastfeeding and intelligence.

PMID- 1348313
TI  - Use of intravenous urogram in hypertension.

PMID- 1348314
TI  - HCV confirmatory testing of blood donors.

PMID- 1348315
TI  - HCV confirmatory testing of blood donors.

PMID- 1348316
TI  - HCV confirmatory testing of blood donors.

PMID- 1348317
TI  - 4-Fluoroquinolones and Lactobacillus spp as emerging pathogens.

PMID- 1348318
TI  - Antiphospholipid antibodies in patients with previous myocardial infarction.

PMID- 1348319
TI  - Orchidopexy and transformation of seminoma to non-seminoma.

PMID- 1348320
TI  - Monoclonal endotoxin antibody in meningococcal sepsis.

PMID- 1348321
TI  - Penicillin-resistant pneumococcal meningitis.

PMID- 1348322
TI  - Penicillin-resistant pneumococcal meningitis.

PMID- 1348323
TI  - Chemoprophylaxis for infective endocarditis.

PMID- 1348324
TI  - Chemoprophylaxis for skin surgery.

PMID- 1348325
TI  - Subzonal insemination.

PMID- 1348326
TI  - Systemic release of interferon-gamma in drug-induced cutaneous vasculitis.

PMID- 1348327
TI  - Health in tobacco control.

PMID- 1348328
TI  - London's hospitals: a fossil's reply.

PMID- 1348329
TI  - Impact of staffing structure on hospital laboratory productivity and cost.

PMID- 1348330
TI  - AZT: zidovudine or azathioprine?

PMID- 1348331
TI  - Ethical emergencies.

PMID- 1348332
TI  - Language tests for EC doctors.

PMID- 1348333
TI  - A short list at the Royal Free.

PMID- 1348334
TI  - Hypernatraemia, acute diarrhoea, and oral rehydration therapy.

PMID- 1348335
TI  - Treatment of early breast cancer.

PMID- 1348336
TI  - PCR for confirmation of Brazilian purpuric fever.

PMID- 1348338
TI  - Containment of drug resistant malaria.

PMID- 1348337
TI  - Vibrio cholerae non-O1 in sewage lagoons and seasonality in Peru cholera
      epidemic.

PMID- 1348339
TI  - Kaposi's sarcoma and insertive rimming.

PMID- 1348340
TI  - Human papillomavirus type 16 and Kaposi's sarcoma.

PMID- 1348341
TI  - Heart disease in myotonic dystrophy.

PMID- 1348342
TI  - Human papillomavirus type 16 and Kaposi's sarcoma.

PMID- 1348343
TI  - Kaposi's sarcoma epidemiology.

PMID- 1348344
TI  - Celiprolol.

PMID- 1348345
TI  - Tamoxifen-associated hepatocellular damage and agranulocytosis.

PMID- 1348346
TI  - Retrospective diagnosis of small epidemic of haemorrhagic fever with renal
      syndrome.

PMID- 1348347
TI  - Renal allograft failure and antibodies to epithelial cells.

PMID- 1348348
TI  - Evaluating an abnormal urinary steroid profile.

PMID- 1348349
TI  - Prevalence of HLA B7 in MS with symptomatic uveitis.

PMID- 1348350
TI  - [The 92nd Congress of the Japan Surgical Society. March 25-27, 1992, Tokyo,
      Japan. Abstracts].

PMID- 1348351
TI  - Effect of LY 171555 and CY 208-243 on tremor suppression in the MPTP monkey model
      of parkinsonism.
AB  - The antitremor effect of the D2 agonist LY 171555 and of the D1 agonist CY 208
      243 alone and in combination was tested in a monkey previously rendered
      parkinsonian by MPTP and displaying exceptionally a rest tremor in the limbs. The
      D2 agonist suppressed rest tremor in a dose-dependent fashion. The D1 agonist by
      itself had no effect but it potentiated the effect of a small dose of LY 171555.

PMID- 1348352
TI  - Tardive tremor.
AB  - A variety of hyperkinetic movement disorders has been associated with the use of
      neuroleptics (dopamine receptor blocking drugs), but tardive tremor has not been
      previously documented. We describe five patients in whom tremor occurred after
      chronic treatment with neuroleptics, was aggravated by and persisted after
      neuroleptic withdrawal, and improved after treatment with the dopamine depleting
      drug tetrabenazine. This involuntary oscillatory movement, with a frequency range
      of 3-5 Hz, was most prominent during maintenance of a posture, but was also
      present at rest and during a goal-directed movement. The tremor was accompanied
      by other tardive movement disorders, including akathisia, chorea, dystonia,
      myoclonus, and stereotypy. There was no family history or other explanation for
      tremor in these patients. We suggest that this hitherto unreported movement
      disorder is best termed "tardive tremor."

PMID- 1348353
TI  - Is yeast TCP1 a chaperonin?

PMID- 1348354
TI  - Evaluation of some substrates and potential inhibitors of tissue pyroglutamyl
      aminopeptidase I.
AB  - A fluorometric enzyme assay was developed to evaluate the ability of a variety of
      compounds to bind to and/or inhibit pyroglutamyl aminopeptidase I. Among these
      compounds were a series of chloromethyl ketone analogues of thyrotropin releasing
      hormone (TRH) which had previously been shown to possess TRH-like activity in the
      central nervous system and have now been found to be good inhibitors of
      pyroglutamyl aminopeptidase. Thus, it is suggested that the observed TRH-like CNS
      activity could derive indirectly from inhibition of endogenous TRH degradation by
      pyroglutamyl aminopeptidase I.

PMID- 1348356
TI  - Fecal chymotrypsin assay during H2-blocker treatment.

PMID- 1348355
TI  - [Cutaneous lesion associated with multiple endocrine neoplasms type 2A (Sipple's
      syndrome). An early clinical marker].
AB  - We report the association of a cutaneous lesion with multiple endocrine neoplasia
      type 2A (MEN 2A) in three patients from a French family. These lesions are very
      similar to those previously described in an Italian and an American MEN 2A family
      and called cutaneous lichen amyloidosis. In all three families the patients
      presented with a pruritic and pigmented cutaneous lesion localized unilaterally
      on the upper back. However, in the French family the patients also complained of
      paroxysmal pain in the same area, in which we could elicit a touch hypoesthesia
      and pain hyperesthesia. Such an association of cutaneous and neurological
      features in the upper back is known as Notalgia Paresthetica (NP). NP is believed
      to represent a neuropathy of the posterior dorsal nerve rami. Unlike the two
      previously reported families, the histological, immunohistochemical and
      ultrastructural analysis of the skin biopsies of the French patients did not show
      any amyloid material. This suggests that the presence of amyloid may not be a
      constant feature of the cutaneous lesions associated with MEN 2A. We consider
      these lesions as a form of dorsal neuropathy rather than a cutaneous lichen
      amyloidosis. Whatever their origin, these cutaneous lesion usually precede the
      appearance of the neoplastic lesions of MEN 2A. They may act as an early clinical
      marker that must be searched for in each subject at risk for MEN 2A. In addition,
      all patients presenting with NP should be screened for MEN 2A.

PMID- 1348357
TI  - Exocrine pancreatic insufficiency and pancreatic fibrosis due to duodenal
      somatostatinoma in a patient with neurofibromatosis.
AB  - A case of duodenal somatostatinoma is described in a patient with Von
      Recklinghausen neurofibromatosis. The patient presented with exocrine pancreatic
      insufficiency, probably due to distal obstruction of the pancreatic duct by the
      tumor. Preoperative evaluation with calcium-pentagastrin and tolbutamide
      stimulation tests were nondiagnostic. At laparotomy, local excision of the tumor
      was performed. Pathological findings were compatible with duodenal
      somatostatinoma, causing pancreatic fibrosis. Somatostatin extracted from the
      tumor coeluted with the somatostatin-14 standard on high performance liquid
      chromatography (HPLC).

PMID- 1348358
TI  - Multiple sulfatase deficiency: catalytically inactive sulfatases are expressed
      from retrovirally introduced sulfatase cDNAs.
AB  - Multiple sulfatase deficiency (MSD) is an inherited lysosomal storage disease
      characterized by the deficiency of at least seven sulfatases. The basic defect in
      MSD is thought to be in a post-translational modification common to all
      sulfatases. In accordance with this concept, RNAs of normal size and amount were
      detected in MSD fibroblasts for three sulfatases tested. cDNAs encoding
      arylsulfatase A, arylsulfatase B, or steroid sulfatase were introduced into MSD
      fibroblasts and fibroblasts with a single sulfatase deficiency by retroviral gene
      transfer. Infected fibroblasts overexpressed the respective sulfatase
      polypeptides. While in single-sulfatase-deficiency fibroblasts a concomitant
      increase of sulfatase activities was observed, MSD fibroblasts expressed
      sulfatase polypeptides with a severely diminished catalytic activity. From these
      results we conclude that the mutation in MSD severely decreases the capacity of a
      co- or post-translational process that renders sulfatases enzymatically active or
      prevents their premature inactivation.

PMID- 1348359
TI  - Pituitary hyperplasia induced by ectopic expression of nerve growth factor.
AB  - Nerve growth factor (NGF) cDNA was fused to the rat prolactin promoter to induce
      its ectopic expression in pituitary lactotrophs of transgenic mice. High-level
      expression of both RNA and functional protein was achieved in two pedigrees.
      Pituitary cells from these animals secreted biologically active NGF that was
      capable of inducing rapid differentiation of cocultured PC12 pheochromocytoma
      cells. Despite this robust expression, transgenic pituitaries failed to show any
      detectable increase in neuronal innervation. Unexpectedly, we observed a dramatic
      hyperplasia of lactotrophs resulting in pituitaries 10-100 times larger than
      normal. These results suggest that NGF, in addition to its previously described
      effects, may act as a new class of mitogen, with a potential role in oncogenesis.

PMID- 1348361
TI  - Hox-1.11 and Hox-4.9 homeobox genes.
AB  - Mouse Hox-1.11 and Hox-4.9 genes were cloned, and the nucleotide sequences of the
      homeobox regions were determined. In addition, nucleotide sequence analysis of
      the homeobox regions of cloned Hox-4.3 and Hox-4.2 genomic DNA revealed some
      differences in nucleotide sequences and in the deduced homeodomain amino acid
      sequences compared with the sequences that have been reported.

PMID- 1348360
TI  - Demonstration of processing and recycling of biologically active V1 vasopressin
      receptors in vascular smooth muscle.
AB  - The present study examines the binding and postbinding cellular processing and
      recycling of the V1 arginine vasopressin (AVP) receptor in cultured vascular
      smooth muscle cells (VSMCs). The surface binding of AVP to VSMCs was temperature
      dependent and reached equilibrium within 60 min at 4 degrees C. Displacement
      studies with unlabeled AVP or a specific V1 AVP antagonist revealed a single
      class of V1 receptors (Bmax, 1.99 pmol [corrected] per mg of protein; Kd, 2.15
      nM). Incubation of VSMCs with unlabeled 10 nM AVP to promote receptor
      internalization resulted in a time- and temperature-dependent loss of AVP surface
      binding. At 37 degrees C, maximum loss of binding sites (65%) occurred within 20
      min. Recovery of AVP binding occurred rapidly (t1/2, 15-20 min at room
      temperature) and was uninfluenced by inhibiting protein synthesis with
      cycloheximide. Pretreating VSMCs with chloroquine prevented AVP receptor
      recycling, indicating that the AVP-receptor complex requires endosomal
      processing. The biological competence of the recycled AVP receptor was shown by
      AVP-induced Ca2+ uptake. The results of these studies therefore indicate that,
      after surface binding, the AVP-receptor complex internalizes and dissociates in
      an endosomal compartment. It is demonstrated that in VSMCs biologically active V1
      AVP receptors recycle back to the cell surface, thus attenuating the loss of AVP
      surface binding sites.

PMID- 1348362
TI  - Oral antilymphocyte activity and induction of apoptosis by 2-chloro-2'-arabino
      fluoro-2'-deoxyadenosine.
AB  - 2-Chlorodeoxyadenosine (CdA) is active in chronic lymphocytic leukemia, hairy
      cell leukemia, and low-grade lymphomas. In part, this spectrum of activity may be
      attributable to the selective toxicity of CdA to nondividing lymphocytes and
      monocytes. However, CdA is unstable at acidic pH and is degraded by bacterial
      nucleoside phosphorylases. The present experiments demonstrate that the 2'
      arabino-fluoro derivative of CdA, designated CAFdA, is also directly toxic to
      quiescent lymphocytes and macrophages. Unlike CdA, CAFdA was stable at pH 2 and
      resisted degradation by Escherichia coli nucleoside phosphorylase. Cell killing
      was preceded by the formation of DNA strand breaks and could be prevented by
      supplementation of the medium with deoxycytidine. The initial DNA damage
      initiated the pattern of oligonucleosomal DNA fragmentation characteristic of
      apoptosis. Mutant lymphoblasts, deficient in deoxycytidine kinase, with elevated
      cytoplasmic 5'-nucleotidase, or with expanded deoxynucleotide pools secondary to
      increased ribonucleotide reductase activity, were cross-resistant to both CAFdA
      and CdA toxicity. One-week oral treatment with CAFdA (1 mg/ml in drinking water)
      achieved an average plasma concentration of 0.56 microM and eliminated 90% of
      chronic lymphocytic leukemia cells transplanted into severe combined
      immunodeficiency (scid) mice. Under the same conditions, CdA was much less
      active. Collectively, these results suggest that CAFdA could be effective as an
      oral agent in indolent lymphoproliferative diseases and in autoimmune diseases
      where lymphocyte and monocyte depletion is desirable.

PMID- 1348363
TI  - Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in
      infected cell lines and in primary uncultured cells from patients with adult T
      cell leukemia/lymphoma and healthy carriers.
AB  - Although human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent
      of adult T-cell leukemia/lymphoma (ATL), the role of viral gene expression in the
      progression to and maintenance of the leukemic state in vivo is unclear because
      of the inability of most previous studies to readily detect HTLV-I RNA in
      infected individuals. By using the reverse transcriptase-polymerase chain
      reaction, we detected spliced messages for the HTLV-I pX regulatory genes in
      primary uncultured cells from ATL patients and healthy asymptomatic carriers. In
      addition to the expected doubly spliced pX message, three alternatively spliced
      mRNAs were demonstrated (pX delta 17, pX-p21rex, and pX-orfII mRNAs, where orf =
      open reading frame). The same splice sites were shown in the messages from
      uncultured ATL cells and from the HTLV-I-producing C10/MJ cell line.
      Alternatively spliced pX mRNAs have the potential to code for known and putative
      pX gene products. Among the transcripts is a monocistronic mRNA likely to code
      for p21rex (pX-p21rex mRNA). Since alternative splicing of HTLV-I pX mRNA can be
      found in primary uncultured cells, it is likely to have a functional significance
      in vivo. This suggests possible roles for HTLV-I gene expression in the
      progression to and maintenance of ATL, as well as in the phase preceding it.

PMID- 1348364
TI  - High resistance to cisplatin in human ovarian cancer cell lines is associated
      with marked increase of glutathione synthesis.
AB  - Exposure of human ovarian tumor cell lines to cisplatin led to development of
      cell lines that exhibited increasing degrees of drug resistance, which were
      closely correlated with increase of the levels of cellular glutathione. Cell
      lines were obtained that showed 30- to 1000-fold increases in resistance; these
      cells also had strikingly increased (13- to 50-fold) levels of glutathione as
      compared with the drug-sensitive cells of origin. These levels of resistance to
      cisplatin and the cellular glutathione levels are substantially greater than
      previously reported. Very high cisplatin resistance was associated with enhanced
      expression of mRNAs for gamma-glutamylcysteine synthetase and gamma-glutamyl
      transpeptidase; immunoblots showed increase of gamma-glutamylcysteine synthetase
      but not of glutathione synthetase. Glutathione S-transferase activity was
      unaffected, as determined with chlorodinitrobenzene as a substrate. These studies
      suggest the potential value of examining regulation of glutathione synthesis as
      an indicator of clinical prognosis. The highly resistant cell lines are proving
      useful for studying the multiple mechanisms by which tumor cells acquire drug-
      and radiation-resistance.

PMID- 1348365
TI  - The effects of dietary restriction on immune function and development of
      autoimmune disease in BXSB mice.
AB  - Chronic energy intake restriction (CEIR) prolonged the median life span and
      inhibited autoimmunity and development of autoimmune disease in BXSB mice, as has
      been established for mice of several other autoimmune-prone, short-lived strains.
      Whether imposed just after weaning or delayed until manifestations of disease had
      appeared, CEIR inhibited or reversed development of autoimmunity and immune
      complex-based renal disease in male BXSB mice. CEIR also prevented the formation
      of anti-DNA antibodies and prevented the increase in circulating immune complex
      levels that is typically observed in male mice of this strain. Moreover, CEIR
      inhibited development of splenomegaly and prevented the normal age-associated
      decline of a number of immunological functions, including interleukin 2
      production, cell-mediated cytotoxic responses, and mixed lymphocyte reactivity.
      The observed improvement in cell-mediated immune responses was attributed largely
      to the capacity of CEIR to inhibit development of the splenomegaly that occurs
      concomitant with expansion of a non-T, non-B lymphoid cell population. These
      findings emphasize that CEIR, even when imposed relatively late in life in BXSB
      mice, can influence expression of autoimmunities and autoimmune diseases of
      different genetic origins and presumed pathogenetic bases.

PMID- 1348367
TI  - Behavioural and electrophysiological studies of entorhinal cortex lesions in the
      rat.
AB  - Bilateral ibotenic acid injections aimed at the entorhinal cortex (EC) lesioned
      the EC and subiculum in 30% of animals (group EC/S) and caused additional
      hippocampal damage in 50% (group RH). Both lesions increased acetylcholinesterase
      (AChE) staining in the intermediate molecular layer of the dentate gyrus. EC/S
      lesions increased diurnal deep sleep and the incidence of spindles but decreased
      REM sleep. RH lesions increased nocturnal deep sleep and decreased nocturnal
      quiet sleep. Both lesions reduced power over the theta frequency range from 6-10
      Hz for epochs of REM sleep and quiet waking but not deep sleep. Peak frequency
      was unaffected. The RH group and a subset of the EC/S group were nocturnally, but
      not diurnally, hyperactive. Six weeks after the lesion there was no evidence for
      hyperactivity in a novel open field. The EC/S lesion impaired exploration as
      indicated by reduced motility and rearing in an open field and by the failure of
      EC/S-lesioned rats to increase contact time in response to a novel olfactory cue.
      Place navigation learning in a Morris maze was not affected by EC/S or RH
      lesions. However, when the spatial location of the hidden platform was shifted
      EC/S-lesioned rats were impaired. The sprouting response, reduced theta power and
      exploration deficits resemble those reported following electrolytic lesions, but
      the lack of effect on place navigation learning contrasts with reports of
      impaired spatial learning following electrolytic lesions. The data prompt a
      reexamination of the role which the EC projection to the hippocampus plays in
      spatial learning.

PMID- 1348368
TI  - Anxiolytics not acting at the benzodiazepine receptor: beta blockers.
AB  - 1. Although there is clear evidence for many controlled trials in the past 25
      years that beta blockers are effective in anxiety disorders clear indications for
      their use are lacking. 2. The balance of evidence suggests that the mechanism of
      action of beta-blocking drugs is through peripheral blockade of beta-mediated
      symptoms. 3. Most evidence to the efficacy of beta-blockers comes from study of
      their use in generalized anxiety and in acute stress. 4. Because beta-blockers
      carry no risks of pharmacological dependence they may be preferred to many other
      anti-anxiety drugs.

PMID- 1348366
TI  - Memory cell generation ablated by soluble protein antigen by means of effects on
      T- and B-lymphocyte compartments.
AB  - Adult C57BL/6 mice were injected with 100 micrograms of soluble, freshly
      deaggregated human serum albumin (HSA) to produce partial immunologic tolerance.
      Uninjected normal control (N) mice contain only approximately 100 B cells in
      their spleens with the capacity to (i) be activated in vitro into clonal
      proliferation by Escherichia coli lipopolysaccharide plus interleukins 2, 4, and
      5, (ii) form IgG1 as well as IgM antibody, and (iii) display specificity for HSA
      when only IgG1 is allowed to score in an enzyme-linked immunosorbent assay
      (ELISA). Such N mice generate approximately 50,000 clonable anti-HSA IgG1
      antibody-forming cell precursors in their spleens after T-dependent immunization
      with HSA absorbed onto alum and given with Bordetella pertussis adjuvant. Mice
      preinjected with soluble HSA (TOL) generate far fewer anti-HSA IgG1 antibody
      forming cell precursors, termed anti-HSA memory cells. Splenocytes were
      transferred from N or TOL mice into lethally irradiated syngeneic recipients
      together with syngeneic bone marrow. Whereas N splenocytes generated plentiful
      memory cells within 2 weeks in antigenically challenged recipients, TOL
      splenocytes did not. Work with Ly-5 congenic mice ruled out memory cell
      generation from either the host or the bone marrow inoculum within this limited
      time. N T cells plus TOL B cells showed consistently lowered memory cell
      generation. TOL T cells plus N B cells showed an even greater lowering of
      adoptive memory cell generation. Thus the lowered response capacity of TOL mice
      resided in the T- and B-cell compartments. Attempts to show a suppressor
      component within the T-cell population were inconclusive, but a profound defect
      in capacity to respond to HSA in vitro was exhibited by the CD4+ T cells of TOL
      mice. B lymphocytes were harvested from T-dependently immunized mice 5 days after
      challenge, incubated with soluble HSA for 18 hr, and then adoptively transferred
      together with N T cells. The recently activated B cells were not rendered
      tolerant by this manipulation. The results argue for a major T-cell component in
      the process whereby soluble protein antigens ablate affinity maturation and
      memory cell generation.

PMID- 1348369
TI  - Quantitative assessment of psychomotor activity in patients with neuroleptic
      induced akathisia.
AB  - 1. An ambulatory activity monitor with solid-state memory was employed to obtain
      24-hour activity data in 29 neuroleptic-treated hospitalized patients and 9
      normal controls. 2. The activity monitor is a piezoelectric device which was
      strapped to the non-dominant ankle. Activity was recorded in 5-minute epochs
      throughout the 24-hour period. 3. In contrast to patients with mania (N = 15) and
      schizophrenia (N = 4), depressed patients (N = 9) had higher clinical ratings of
      akathisia and lower levels of daytime activity. 4. Manic and depressed patients
      showed a delay of peak activity (= acrophase). 5. Quantifiable alterations in
      rest-activity rhythms may occur in neuroleptic-induced akathisia but measurement
      of activity may be complicated by the patient's psychiatric disorder.

PMID- 1348370
TI  - International regulation of benzodiazepines.
AB  - 1. The UN Convention 1971 on Psychotic substances requires the World Health
      Organization to recommend psychotropic substances for international control. 2.
      This convention is based on evaluating the benefit and risk ratio, in particular
      on the public health and social problems associated with its use. 3. The UN
      Commission on Narcotic Drugs takes a final decision on these recommendations and
      is then binding in countries which are party to the convention. 4. Presently 34
      commercially available benzodiazepines are under international control at minimum
      level, schedule IV of the 1971 convention, to be available on the physicians'
      prescription and not over the counter.

PMID- 1348371
TI  - The second annual PACAP Symposium. Satellite symposium for 21st Annual Meeting of
      the Society for Neuroscience. New Orleans, November 10, 1991. Abstracts.

PMID- 1348372
TI  - Implications for the pharmacotherapy of schizophrenia.

PMID- 1348373
TI  - [Adrenergic receptor--classification, agonists and antagonists].

PMID- 1348374
TI  - HLA-D-region genomic DNA restriction fragments in DRw15 (DR2) familial
      narcolepsy.
AB  - Restriction fragment length polymorphism (RFLP) associated with the three human
      lenkocyte antigen (HLA)-D-region gene-specific cDNA probes (gene-specific DQ
      alpha, DQ beta and DP beta) was evaluated in two Caucasian families from
      southwestern Ontario, each with two confirmed narcoleptic siblings. The special
      feature of the two families is that the affected members are not necessarily
      DRw15 (previously DR2) positive. In family 1, of the two affected sibs one is
      DRw15 positive, whereas in family 2 all members including the two affected sibs
      are DRw15 negative. There is no association between narcolepsy and HLA haplotype
      in the two families. Further, the polymorphic DNA band patterns generated by a
      number of restriction enzymes do not show a relationship with the presence or
      absence of narcolepsy. The probe-specific DNA and patterns however do follow the
      HLA haplotypes associated with the DQ and DR loci. These results suggest that in
      DRw15-negative narcolepsy, the DNA patterns are not informative with respect to
      diagnosing or predicting the presence of narcolepsy. Further, such results argue
      for genetic heterogeneity in narcolepsy, and the role of DRw15 in the development
      of the disease could at best be viewed as contributory and not essential.

PMID- 1348375
TI  - Recent developments in biomodulation: Second International Workshop on
      Gastrointestinal Cancer. Garmisch-Partenkirchen, Germany, February 6-7, 1991.

PMID- 1348377
TI  - The intractable pain treatment act of Texas.
AB  - There is overwhelming evidence that all types of pain, either of malignant or
      nonmalignant origin, are undertreated. This is especially true of patients whose
      pain can only be relieved by strong narcotics. The disciplinary section of the
      Texas Medical Practice Act (MPA) contains ambiguous language that makes
      determining proper standards for the use of narcotics difficult. To clarify this,
      the Intractable Pain Treatment Act (IPTA) allows the use of narcotics to treat
      intractable pain, without regard to the etiology of the pain, and clarifies
      narcotic use standards by defining intractable pain. The IPTA brings Texas law
      more into conformity with federal law, which clearly states that narcotics have a
      proper place in the treatment of intractable pain even if the etiology is not
      established. Reluctance to use narcotics for selected patients with nonmalignant
      painful medical conditions stems from the mistaken belief that they will become
      narcotic "addicts." Data from the medical literature do not support such a
      contention; in fact, just the opposite is supported.

PMID- 1348376
TI  - The Nithsdale schizophrenia surveys. An overview.
AB  - The Nithsdale surveys over a ten year period have examined a community of
      schizophrenic patients. Although almost three-quarters of patients were living
      outside hospital, social and psychiatric disability was considerable, with
      flattening of affect and social withdrawal most prominent. The majority probably
      cause little disturbance to most people in the community. Only 13% of the total
      Nithsdale schizophrenic population were living in a high contact/high Expressed
      Emotion family, the family structure believed to be most conducive to
      schizophrenic relapse. An attempt at family intervention found it difficult to
      engage relatives in treatment; however, where such intervention did take place,
      there was a fall in the total number of relapses. Reassessment found that the
      level of EE was stable in most relatives over a five year period. Patients who
      lived in a high or fluctuating EE home, and who relapsed, did so more often than
      those who lived in a low EE home. Assessment of the prevalence of motor disorders
      secondary to antipsychotic medication found a point prevalence of parkinsonism of
      27%, of tardive dyskinesia (TD) 29%, and of akathisia or pseudoakathisia 23%.
      Only 44% had no movement disorder. Eight percent had persistent TD. Parkinsonism
      was associated with a history of obstetric complications and TD with left
      handedness. An obstetric history obtained from mothers of schizophrenic patients
      found there was no difference in the proportion of schizophrenic patients and
      their sibs who had at least one definite obstetric complication.

PMID- 1348379
TI  - The role of the blood bank in hematopoietic stem cell transplantation.

PMID- 1348378
TI  - [Deaths caused by antidepressive agents and neuroleptics. Risk groups illustrated
      by a forensic material].
AB  - At the Institute of Forensic Medicine, University of Oslo, legal autopsy was
      performed on 153 persons who died from poisoning by neuroleptics and/or
      antidepressants from 1986 to 1989. In one third of the cases, only neuroleptics
      were found at autopsy, and in little less than half of these cases the post
      mortem blood concentrations were considered rather low in relation to the fatal
      outcome. A larger proportion of alcohol abusers were found in the group with low
      post mortem concentrations of neuroleptics than in the rest of the material. This
      group contained mainly men and was further characterized by a high proportion of
      unintentional deaths. In the light of these facts the authors speculate whether
      neuroleptics represent increased risk of sudden death among alcohol abusers. The
      deaths due to an overdose of antidepressants were mostly suicides, and involved
      high post mortem blood concentrations of the drugs.

PMID- 1348380
TI  - A light and electron microscopic study of changes in blood and bone marrow in
      acute hemorrhagic Trypanosoma vivax infection in calves.
AB  - Eleven 6-month-old calves were tsetse fly challenged with a stock of Trypanosoma
      vivax (IL 2337) that causes hemorrhagic infection. The calves were randomly
      euthanatized every 4 to 6 days; two other calves served as controls. Peripheral
      blood changes included anemia, thrombocytopenia, and an initial leukopenia. Later
      in the course of infection, leukocytosis associated with lymphocytosis and
      neutropenia developed. Moderate reticulocytosis (highest mean count 3.6 +/- 3.7%,
      maximum count 9.4%) accompanied the first wave of parasitemia, but poor response
      (highest mean 0.4 +/- 0.0%) occurred during the second wave, despite the
      persistence of severe anemia. Light microscopic examination of bone marrow
      samples showed a drop in the myeloid: erythroid ratio with a decrease in
      granulocytes, particularly metamyelocytes, bands, and segmenters. Increase in
      lymphocyte counts corresponded with the appearance of lymphoid nodules within the
      marrow. Megakaryocytic volume increased significantly in infected animals, and
      some megakaryocytes showed emperipolesis of red cells, neutrophils, and
      lymphocytes. Transmission electron microscopic examination of the bone marrow
      revealed that trypanosomes had crossed the sinusoidal endothelium into the
      hematopoietic compartment as early as the second day of parasitemia. Macrophages
      proliferated in the bone marrow; and from the second day of parasitemia until the
      end of the experimental infection, on day 46, the macrophages had phagocytosed
      normoblasts, eosinophil and neutrophil myelocytes, metamyelocytes, bands, and
      segmenters, as well as reticulocytes, erythrocytes, and thrombocytes. Therefore,
      dyserythropoiesis and dysgranulocytopoiesis were responsible, in part, for the
      observed anemia and granulocytopenia, respectively.

PMID- 1348381
TI  - Summer mastitis in heifers: studies on the seasonal occurrence of Actinomyces
      pyogenes, Peptostreptococcus indolicus and Bacteroidaceae in clinically healthy
      cattle in Denmark.
AB  - With the aim of investigating the seasonal occurrence of Actinomyces pyogenes,
      Peptostreptococcus indolicus, Bacteroides melaninogenicus ss. levii and
      Fusobacterium necrophorum, and thus the potential for development of summer
      mastitis, clinically healthy Danish Holstein-Friesian heifers due to calve in the
      autumn were sampled from the teat tip, the conjunctiva and the oral cavity at 2-6
      week intervals from 1979 to 1981. The overall isolation rates of F. necrophorum,
      P. indolicus and B. melaninogenicus ss. levii, in order of significance, were
      significantly higher during the pasture period whereas no differences in
      isolation rates of A. pyogenes between housed and pastured animals were detected.
      F. necrophorum was recovered almost exclusively from the oral cavity, P.
      indolicus and A. pyogenes occurred most frequently in samples from the teat skin,
      whereas isolates of B. melaninogenicus ss. levii were evenly distributed between
      conjunctiva and teat tip samples. A distinct seasonal pattern of the isolation
      rates of summer mastitis pathogens was recorded, which corresponded closely to
      the seasonal activity of symbovine insects, in particular the headfly Hydrotaea
      irritans (Fallen). However, the high proportion of clinically healthy bacterial
      carriers as compared with the incidence of clinical disease strongly suggests
      that as yet unknown contributing or triggering factors, apart from the mere
      presence of the relevant bacterial species, are required for the establishment
      and development of clinical summer mastitis.

PMID- 1348383
TI  - [German Association for the Study of the Liver (GASL), 8th meeting. Marburg,
      January 24-25, 1992. Abstracts].

PMID- 1348382
TI  - [The effect of duodenum-preserving pancreatic head resection on the endocrine
      pancreas function in patients with chronic head pancreatitis].
AB  - In a prospective clinical-experimental study, 15 patients with chronic
      pancreatitis operated consecutively due to severe pain were examined for the
      effects of a duodenum-preserving resection of the pancreas head on endocrine
      pancreas function. This was done by means of oral and intravenous glucose
      tolerance testing before the operation, on the 10th or 11th postoperative day,
      and three months after the operation. In addition to glucose levels in the
      peripheral venous blood, levels of insulin, C-peptide, glucagon, somatostatin,
      and pancreatic polypeptide were determined. As indicated by the k-value, glucose
      tolerance improved postoperatively in 11 patients; two patients showed no change,
      and one patient was worse. Only one patient developed evident diabetes mellitus
      immediately postoperatively. The pre- and postoperative levels of insulin and C
      peptide showed no significant differences. The fasting levels of glucagon were
      significantly lower postoperatively than before the operation (2p less than
      0.01). Duodenum-preserving pancreas head resection led to improvement of the
      glucose tolerance in the majority of patients; a deterioration was observed only
      in two cases.

PMID- 1348384
TI  - [Smith's fracture. A radiological and functional follow-up study of 62 primary
      and post-primary surgically treated fractures].
AB  - The reversed Barton fracture of the distal radius is rare. In the literature
      there is a rate of 3 to 20.5% of all distal radius fractures. Whereas the
      reposition is simple, the reduction is difficult. This retrospective report about
      the treatment by osteosynthesis in the years between 1977 to 1987 in the
      "Berufsgenossenschaftliche Unfallklinik" Tubingen demonstrates a direct
      correlation between radiological and functional results. That means in
      consequence that internal fixation by using a small palmar T-plate is the
      favorable therapy.

PMID- 1348385
TI  - [Dorsal compression fractures of the distal radius metaphysis. Long-term follow
      up with conservative therapy].
AB  - Conservatively treated compressed fractures of the distal radius dorsal
      metaphysis healed despite primarily good reduction and consequent treatment with
      a decrease in dorsal length. The amount of this decline depends on the primary
      loss of dorsal length. If the fracture showed a loss of dorsal length at the time
      of the accident of up to 2 mm, the long-term results were almost anatomical. If
      there was primarily a larger loss of dorsal length, a decline of the distal
      fragment into the dorsal cave resulted. Most of the dorsal length regained after
      reduction was lost when the cast was removed. The long-term follow-up
      examinations were made after about 9 years.

PMID- 1348386
TI  - [The value of external fixation in the treatment of radius fractures of the
      distal end].
AB  - 40 distal radial fractures were treated using either and external fixator alone
      or in combination with other osteosynthetic methods. 31 fractures were available
      for review with an average follow up 30.3 months. They were assessed according to
      Pfeiffer's criteria. The functional result was very good or good in 19, moderate
      in 5 and poor in 7 of these fractures. The functional outcome was related to the
      degree of articular damage, quality of joint reconstruction and the presence of
      algodystrophy.

PMID- 1348387
TI  - [The treatment of distal radius fractures using the external fixator].
AB  - This is a report on the stabilisation of fractures of the distal end of the
      radius type C2 and C3 and open fractures by external fixator. Between 1982 and
      1989 38 patients with 43 fractures were treated. A follow-up was done 8 to 80
      months after operation including 35 patients. 14 patients were polytraumatised.
      Especially in this group of patients, the advantages of this procedure can be
      seen. This advantages are a small stress for the patient, involving only a short
      time of assembling of the external fixator besides a high stability of the
      system. Our results show, as well as the results of the literature, that the
      external fixator has its place in a differentiated therapeutic concept of
      intraarticular fractures, open fractures and fractures with a defect of the
      distal radius.

PMID- 1348388
TI  - [Fixation of the styloid process of the ulna in dislocation fractures of the
      hand].

PMID- 1348389
TI  - [Biomechanical aspects of the over-the-top reconstruction of the anterior
      cruciate ligament].
AB  - Strain characteristics of anterior cruciate ligament grafts inserted in the over
      the-top technique were studied in an in-vitro model. A cruciate ligament attached
      at the center of the anatomical insertion sites provides a constant preload and
      accomplishes the principle of isometry during the whole range of motion. In
      contrast, the over-the-top reconstructed ligament shows an increasing laxity
      proportional to the degree of joint flexion due to an approach of the attachment
      areas. These observations indicate that a sufficient ligament function is not
      provided so that the over-the-top reconstruction cannot be recommended as method
      of choice.

PMID- 1348390
TI  - [The concepts "adequacy" and "suitability" in medical expert testimony].

PMID- 1348391
TI  - [Recurrent malignant fibrous histiocytoma of the forearm].

PMID- 1348392
TI  - The current management of the patient with uncomplicated myocardial infarction.

PMID- 1348393
TI  - The molecular genetics of lung cancer.

PMID- 1348394
TI  - [Ocular hypotensive effect of alpha-adrenoceptor agonist and antagonist in the
      conscious pigmented rabbit].
AB  - It has been reported that some of the topically-used antiglaucomatics have a
      central ocular hypotensive effect. In this study, the influence of topical and
      intracerebroventricular (i.c.v.) administration of phenylephrine, clonidine,
      guanfacine, prazosin, yohimbine on the intraocular pressure (IOP) was
      investigated in the rabbit. Male pigmented rabbits were used throughout the
      experiments. For measurement of IOP, an applanation pneumatonograph was used. By
      unilateral topical administration of phenylephrine, an increase in IOP in the eye
      in which instillation was performed was observed. On the other hand, a slight
      decrease in IOP was observed by similar treatment of prazosin and yohimbine. No
      significant change of IOP in the contralateral eye was observed with these drugs.
      On the contrary, unilateral topical administration of clonidine or guanfacine
      decreased the IOP of both eyes. Furthermore, the decrease of IOP was more
      remarkable in the contralateral eye compared to the eye which received
      instillation. The IOP of both eyes was decreased in a dose-related fashion by
      i.c.v. administration of clonidine or guanfacine. The ocular hypotensive effects
      of clonidine were diminished by the pretreatment by i.c.v. administration with
      yohimbine. These results suggest that the ocular hypotensive effect of clonidine
      and guanfacine is due to their alpha 2-adrenoceptor stimulation in the central
      nervous system.

PMID- 1348395
TI  - T-lymphocyte activation in adult-onset idiopathic hypoparathyroidism.
AB  - PURPOSE: Patients with adult-onset idiopathic hypoparathyroidism (AOIH) often
      have antibodies against the parathyroid glands and other tissues, suggestive of
      immune activation. The purpose of this study was to determine whether T-cell
      activation is also a component of the endocrine disease. PATIENTS AND METHODS: We
      identified eight patients with idiopathic hypoparathyroidism diagnosed after the
      age of 30 years at two tertiary care centers and evaluated peripheral blood
      lymphocyte subset phenotype frequencies using monoclonal antibodies and flow
      cytometry. Control subjects were 13 patients with Graves' disease (five
      thyrotoxic and eight euthyroid) and 110 healthy volunteers. In two of the
      patients with AOIH, we also determined the mitogenic response to parathyroid cell
      membranes in peripheral lymphocytes. RESULTS: Patients with AOIH had higher than
      normal frequencies of the following phenotypes (p less than 0.05 versus controls,
      one-way analysis of variance): CD4, helper T cells; CD29/CD4, inducer of helper T
      cells; CD16 and CD56, natural killer cells; and CD3/DR, activated T cells
      coexpressing DR. Patients with Graves' disease had significantly higher than
      control frequencies of CD25 (T cells bearing the interleukin-2 receptor), CD3/DR,
      and CD26 (also a marker of T-cell activation); whereas the frequency of CD29/CD4
      was significantly less than the control frequency. Neither of the two AOIH
      patients tested showed lymphocyte proliferation in response to parathyroid or
      thyroid cell membrane fractions. CONCLUSIONS: Generalized T-cell activation
      represents a novel feature associated with AOIH. Although we could not
      demonstrate parathyroid-specific lymphocyte clonal expansion, these data are
      suggestive of a generalized immune disturbance possibly related to autoimmunity,
      in which one of the manifestations is hypoparathyroidism.

PMID- 1348396
TI  - Prophylactic use of apraclonidine for intraocular pressure increase after Nd:YAG
      capsulotomies.
AB  - We evaluated the prophylactic effect of 1% apraclonidine HCl in controlling the
      increase in intraocular pressure after Nd:YAG posterior capsulotomy in a large,
      multicenter double-masked clinical trial. One hundred sixty-four patients were
      enrolled into the apraclonidine-treated group, and 165 into the vehicle-treated
      group. The incidence of increase in intraocular pressure (greater than 5 mm Hg)
      in the apraclonidine-treated group (7%, 11 of 163 patients) was significantly
      less than that in the vehicle-treated group (39%, 64 of 164 patients). Similarly,
      the mean maximal change in intraocular pressure in the apraclonidine-treated
      group (1.3-mm Hg decrease) was significantly different from the increase in the
      vehicle-treated group (5.3-mm Hg increase). Few adverse reactions were observed.
      The risk for significant loss of visual function after Nd:YAG laser posterior
      capsulotomy, combined with the efficacy and relative safety of prophylactic
      apraclonidine, suggest its addition to the treatment armamentarium.

PMID- 1348397
TI  - Effect of mesangiolysis on autoregulation of renal blood flow and glomerular
      filtration rate in rats.
AB  - Interlobular arteries and afferent arterioles are involved in autoregulation of
      renal blood flow (RBF) and glomerular filtration rate (GFR). The question of
      whether the contractile mesangial cells are also involved in autoregulation was
      investigated in Wistar rats. Autoregulation of RBF was examined before and 1 h
      after infusion of antithymocyte (anti-Thy 1-1) antibodies, and both RBF and GFR
      autoregulation were examined 30 h after the infusion of antibodies. Mesangial
      cell destruction was present 30 h after the infusion of antibodies. The
      angiotensin II-induced contraction of isolated glomeruli (70% of control volume,
      P less than 0.001) was abolished after the glomeruli had been exposed to anti-Thy
      1-1 in vitro. RBF, as well as the lower limit of RBF autoregulation, were not
      different from control 30 h after the infusion (82 +/- 5 vs. 79 +/- 4 mmHg, P
      greater than 0.10). Autoregulation of GFR was maintained in the control group but
      was restricted in the experimental group (autoregulatory index: 0.71 +/- 0.42 for
      left kidney, 0.02 +/- 0.35 for control; P less than 0.05). The afferent
      arteriolar diameter was unchanged 30 h after the infusion of antibodies (17.8 +/-
      0.8 vs. 17.6 +/- 0.4 microns, P greater than 0.10). One hour after infusion of
      the antibodies, RBF autoregulation was normal. It is concluded that mesangial
      cells do not seem to be involved in RBF autoregulation, but may in part influence
      autoregulation of GFR during pressure reduction.

PMID- 1348398
TI  - Comparison of responses to sarafotoxins 6a and 6c in pulmonary and systemic
      vascular beds.
AB  - Cardiovascular and pulmonary responses to sarafotoxin (S) 6a and S6c were
      investigated in the anesthetized cat. Intravenous injections of the peptides in
      doses of 0.1-1.0 nmol/kg caused decreases or biphasic changes in arterial
      pressure (AP) and increases in central venous pressure, pulmonary arterial
      pressure (PAP), and cardiac output (CO). Secondary decreases in CO were observed
      in response to higher doses, and biphasic changes in systemic (SVR) and pulmonary
      (PVR) vascular resistances were observed. Under constant-flow conditions, the
      peptides only increased pulmonary lobar arterial perfusion pressure and lobar
      vascular resistance. AP responses to S6a, S6c, endothelin (ET)-1, ET-2,
      vasoactive intestinal contractor (VIC), and Lys7-ET-1 were similar, whereas AP
      responses to S6b and ET-3 were similar. S6a, S6b, S6c, ET-1, ET-2, ET-3, VIC,
      Lys7-ET-1, and big ET-1 increased PAP. S6a and S6c increased distal aortic and
      superior mesenteric arterial (SMA) blood flow and caused biphasic changes at the
      highest doses. Under constant-flow conditions, S6a and S6c produced dose
      dependent biphasic changes in hindquarters perfusion pressure. Changes in SVR and
      PVR in response to the peptide were not affected by hexamethonium, glyburide, or
      meclofenamate, indicating that responses are independent of autonomic reflexes,
      activation of ATP-regulated K+ channels, or release of cyclooxygenase products.
      In contrast, N-nitro-L-arginine methyl ester decreased hindquarters vasodilator
      response to S6a and S6c. The present data show that S6a and S6c produce both
      vasodilation and vasoconstriction in the systemic vascular bed and increase lobar
      vascular resistance and that hindquarters vasodilator responses are mediated, in
      part, by the release of endothelium-derived relaxing factor.

PMID- 1348399
TI  - Influence of opioids on CSF vasopressin concentration in newborn pigs.
AB  - This study was designed to determine the influence of opioids on periarachnoid
      cortical cerebrospinal fluid (CSF) vasopressin concentration in newborn pigs
      equipped with closed cranial windows. Topical dynorphin-(1-13) produced tone
      dependent pial arterial responses (dilation during normotension, constriction
      when cerebrovascular tone was decreased by hypotension). Dynorphin-(1-13)
      increased periarachnoid cortical CSF vasopressin concentrations in both
      normotensive and hypotensive piglets (5 +/- 1, 11 +/- 1, and 233 +/- 27 microU/ml
      for control, 10(-10), and 10(-6) M dynorphin-(1-13) during normotension,
      respectively). Dynorphin-(1-8) and U 50488H, a purported selective kappa-opioid
      receptor agonist, produced similar tone-dependent responses associated with
      smaller increases in CSF vasopressin concentration. beta-Endorphin caused only
      cerebral vasoconstriction associated with modest increases in CSF vasopressin (3
      +/- 1, 5 +/- 1, 9 +/- 2 microU/ml for control, 10(-10), and 10(-6) M beta
      endorphin, respectively). In contrast, methionine enkephalin- and leucine
      enkephalin-induced dilations were not associated with changes in CSF vasopressin
      concentration. Naloxone (1 mg/kg i.v.) blocked both the opioid-induced vascular
      effects and associated changes in CSF vasopressin concentration. Naloxone also
      attenuated the increase in CSF vasopressin concentration in response to
      hemorrhagic hypotension. These data show that dynorphin- and beta-endorphin
      induced cerebrovascular effects are associated with increased CSF vasopressin
      concentration. Furthermore, these data indicate that opioids could contribute to
      the increase in CSF vasopressin concentration observed in response to hemorrhagic
      hypotension.

PMID- 1348400
TI  - Mechanisms of signal transduction for adenosine and ATP in pulmonary vascular
      bed.
AB  - The purpose of the present study was to investigate the contribution of pertussis
      toxin (PTX)-sensitive guanine nucleotide (G) proteins in the pulmonary vascular
      response to adenosine and ATP in the intact cat under conditions of controlled
      pulmonary blood flow and left atrial pressure. Adenosine, ATP, and beta-tau-ATP
      increased lobar arterial pressure in a dose-dependent manner. The pulmonary
      vasoconstrictor response to adenosine was abolished by BW 1433U, a specific
      purinergic receptor (P1) inhibitor, PTX pretreatment, indomethacin, and ONO 3708,
      a thromboxane A2 (TxA2) receptor antagonist. These data suggest that the
      pulmonary vasoconstrictor response to adenosine depends on activation of P1
      purinergic receptors coupled to PTX-sensitive G proteins and subsequent
      metabolism of liberated arachidonic acid to form TxA2. Because each blocking
      agent studied produced similar reductions in the pulmonary vasoconstrictor
      response to ATP without altering the pulmonary vasoconstrictor response to beta
      tau-ATP, the present data suggest that ATP constricts the pulmonary vascular bed,
      in part, by hydrolysis to adenosine. Moreover, the present study suggests that
      both A1 purinoceptors that are linked to PTX-sensitive G proteins as well as P2x
      purinoceptors receptors that are independent of PTX-insensitive G proteins
      mediate the pulmonary vasoconstrictor response to ATP in vivo.

PMID- 1348401
TI  - Neuroendocrine evidence for reduced dopamine receptor sensitivity in alcoholism.
AB  - Postsynaptic dopamine (DA) receptor sensitivity was assessed during abstinence in
      15 male patients with alcohol dependence. The DA receptor sensitivity was
      evaluated using growth hormone (GH) responses to the DA receptor agonist
      apomorphine (0.18-0.24 mg intravenously). The patients were cared for in an
      alcoholism treatment unit for the 2 months prior to the investigation. They were
      carefully controlled for sobriety during this period. Thirteen healthy men were
      used as controls. The maximum GH responses to apomorphine were significantly
      reduced in patients compared with those in the control group. The patients had a
      significantly higher proportion of blunted GH responses. The findings suggest
      reduced postsynaptic DA, possibly D2, receptor sensitivity in abstinent
      alcoholics. The question whether this abnormal DA receptor status is genetically
      determined or acquired after long-term alcohol consumption remains to be
      addressed.

PMID- 1348402
TI  - New alcohol markers--how useful are they in population studies: the Svalbard
      Study 1988-89.
AB  - Regular high consumption of alcohol in selected populations have, with high
      precision, been identified by two new alcohol markers; carbohydrate-deficient
      transferrin and mitochondrial aspartate aminotransferase. To test these markers
      in an unselected population, gamma-glutamyltransferase (GGT), carbohydrate
      deficient transferrin (CDT), and mitochondrial aspartate aminotransferase (mAST)
      were measured in the Norwegian population, 310 males and 171 females, aged 18 to
      60 years, living at Svalbard. Using self-reported alcohol intake as gold
      standard, sensitivity, specificity, positive predictive value, and likelihood
      ratio were estimated according to different cutoff-points for alcohol intake and
      for the tests. In contrast to earlier studies, the sensitivity was in general
      low. With a specificity of 90% or higher, the sensitivity did not exceed 26% for
      any of the tests. Whereas CDT showed its best discriminatory power at lower
      intake of alcohol, GGT discriminated best at higher levels. Parallel and serial
      analysis of CDT and GGT indicated a conditional independence between the tests,
      as well as at higher and at lower levels of alcohol consumption. mAST was judged
      as not suitable in population studies.

PMID- 1348403
TI  - Comparative effects of digoxin and xamoterol on arrhythmias in patients with mild
      to moderate heart failure.
AB  - The prognosis of heart failure patients is poor and as many as half of the deaths
      are sudden and thereby presumably attributable to arrhythmias. In the present
      study the effect of traditional therapy of mild heart failure with digoxin on
      arrhythmias was compared with the effect of xamoterol, a cardioselective beta 1
      partial agonist, which has in addition beta-blocking properties at higher levels
      of sympathetic tone. Fifteen patients (NYHA class II-III) were included in the
      study. After a two-week baseline period they were randomized to digoxin or
      xamoterol for four weeks followed by a two-week washout and another four weeks of
      crossover therapy. Heart rate, blood pressure, and the number of complex
      ventricular premature beats remained essentially unchanged with digoxin. With
      xamoterol heart rate increased from 86 to 93 (ns) but was significantly higher
      during the night in comparison with digoxin. The number of ventricular premature
      beats decreased from 186 +/- 317 to 110 +/- 137 and increased to 130 +/- 175
      after treatment. The number of runs decreased from 11 +/- 35 to 2.7 +/- 5 and
      increased to 5.6 +/- 9 after therapy. In conclusion, no significant effect of
      digoxin or xamoterol on ventricular arrhythmias was found. However, xamoterol
      showed a tendency to reduce simple and complex ventricular arrhythmias in
      patients with mild to moderate heart failure.

PMID- 1348404
TI  - Premenstrual asthma with seasonal variation.
AB  - A 19-year-old woman had premenstrual asthma (PMA) usually from April through
      October each year with normal and regular menstrual cycles. When the monthly
      variation in the patient's PMA between 1984 and 1990 was compared with the
      monthly admissions of children for acute asthma in a hospital in this region,
      there was a great similarity in pattern between the two. Although she had high
      sensitivity to house-dust mites, the monthly pattern of her PMA did not coincide
      with monthly variations in the number of mites in house-dust in her home.

PMID- 1348405
TI  - Efficacy and safety of cetirizine therapy in perennial allergic rhinitis.
AB  - A double-blind, placebo-controlled trial was undertaken to assess the safety and
      efficacy of once daily cetirizine in alleviating the symptoms of perennial
      allergic rhinitis. Subjects were adults with perennial allergic rhinitis,
      characterized by nasal congestion, postnasal discharge, sneezing, rhinorrhea,
      nasal itching, lacrimation, ocular itching, and itching of the roof of the mouth,
      and a total pretreatment symptom severity score of greater than or equal to 8.
      Patients were randomized to treatment with 10 mg cetirizine, 20 mg cetirizine, or
      placebo for 4 weeks. Efficacy was assessed in 215 patients and safety in 216.
      Cetirizine in once daily dosages of 10 or 20 mg proved to be effective in
      relieving the overall symptoms of perennial allergic rhinitis and particularly
      postnasal discharge and sneezing. The 10-mg dose afforded optimal symptomatic
      relief, and the 20-mg dose provided little or no additional benefit. Cetirizine
      was well tolerated, and the frequency of somnolence was not significantly greater
      in patients receiving this drug than in those given placebo.

PMID- 1348406
TI  - Coexpression of CD4 and CD8 on mitogen-activated peripheral blood T cells from
      children with asthma: possible involvement of interleukin 4.
AB  - Mononuclear cells were isolated from the peripheral blood of 28 asthmatic and 18
      healthy children aged 3 to 16 years. The cells were stimulated with
      phytohemagglutinin for 96 hours. Activated cells were detected microscopically by
      MTT staining. Expression of cell surface antigens was detected by indirect immune
      fluorescence using CD4-specific and CD8-specific monoclonal antibodies. Results
      indicate an enhanced expression of CD8 on mitogen-activated T cells from
      asthmatic children compared with cells from healthy controls (median 43% versus
      27%). Further experiments revealed that CD8 is coexpressed with CD4 on activated
      lymphocytes. Coexpression is significantly enhanced with lymphocytes from
      asthmatic patients compared with normal controls. In addition, interleukin 4 is
      able to enhance this coexpression with lymphocytes from healthy but not asthmatic
      children suggesting an in vivo preactivation of lymphocytes from asthmatic
      patients with interleukin 4.

PMID- 1348408
TI  - Surviving gastrointestinal infarction due to polyarteritis nodosa: a rare event.
AB  - Poly arteritis nodosa (PAN) is a systemic vasculitis with a male: female ratio of
      2:1 and a peak incidence in the fifth decade. Small to medium-sized arteries are
      involved by focal transmural inflammatory necrosis. Aneurysms with inflammatory
      destruction of the media also occur. The most frequently involved organs are the
      kidney, heart, lung, liver, and gastrointestinal tract. There are few reported
      cases of ischemic necrosis of the intestine and even fewer survivors. A 22-year
      old woman was transferred to St. Thomas Hospital (Nashville, TN) after resection
      of 80 per cent of the small bowel for ischemic necrosis. She had a history of
      juvenile onset diabetes mellitus, recurrent abdominal pain, and splinter
      hemorrhages. Emergency aortogram and selective mesenteric arteriogram were
      performed. The celiac artery was not visualized and small aneurysms were present
      in the mesenteric and renal arteries. The patient was successfully resuscitated
      from a cardiac arrest in x ray from a cardiac tamponade. Laparotomy was performed
      to determine the viability of the bowel. The celiac, hepatic, and splenic
      arteries were found to be chronically occluded. Pathology of these arteries
      revealed a nonspecific arteritis. At a third operation, several more inches of
      small bowel were removed. Characteristic changes of PAN were present on all small
      bowel specimens. She was treated with high-dose cyclophosphamide and steroids for
      6 months and has continued on low-dose cyclophosphamide. She is now 36 months
      from her original operation and is doing well on oral nutrition. Intestinal
      hemorrhage from aneurysm rupture or gangrene with perforation are
      gastrointestinal complications of PAN that the surgeon may be called upon to
      treat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348407
TI  - Effects of simulated Fowler-Stephens orchiopexy on testicular structure and
      function in rats.
AB  - To determine the effects of the Fowler-Stephens orchiopexy (FSO) on testicular
      structure and function, young rats underwent simulated FSO and concurrent
      contralateral orchiectomy, unilateral orchiectomy, or no operation. Rats were
      killed at 1, 2, 4, 6, 8, and 10 weeks postoperation, and serum testosterone, as
      well as testicular concentrations of the enzymes LDH & SDH, protein markers of
      testicular germinal cell development, were measured at the time of death.
      Although LDH and SDH concentrations decreased by 45 per cent in testes after
      simulated FSO at 4 weeks, control testes showed a 5 per cent increase in these
      enzymes. Serum testosterone decreased to one-fourth the initial value in rats
      after FSO, whereas control rats showed a slight increase. Within 2 weeks after
      simulated FSO, spermatocytes and sperm were sparse and there was marked
      disruption of tubular morphology; after 4 weeks interstitial fibrosis became
      prominent. Only a rare testis with good collateral vessels and resultant good
      histologic appearance and enzyme profile survived the FSO procedure, and these
      testes were considerably smaller than the controls.

PMID- 1348410
TI  - College of American Pathologists Conference XX. New developments in reproductive
      biology. August 21-23, 1991.

PMID- 1348409
TI  - Prognostic value of serum CA 19-9 levels in pancreatic adenocarcinoma.
AB  - Thirty-eight patients with histologically proven pancreatic adenocarcinoma were
      investigated to establish the utility of serum CA 19-9 as a prognostic indicator.
      CA 19-9 assays were performed serially during the course of the disease. In four
      patients with negative Lewis blood type, the CA 19-9 levels remained essentially
      normal throughout the disease course. In the remaining 34 patients, (1) CA 19-9
      levels were significantly lower in patients with tumor size no larger than 5 cm
      in diameter, and in patients with resectable tumors than in those with tumor size
      larger than 5 cm or with unresectable tumors (p less than 0.01). 2) CA 19-9
      levels dropped sharply after resection in all 11 resectable patients, whereas no
      significant change was found after laparotomy without resection. (3) The average
      survival time in seven patients whose CA 19-9 levels returned to normal after
      resection was significantly longer than in those four patients with postoperative
      CA 19-9 levels that decreased but did not return to normal (21.9 versus 8.7
      months, p less than 0.05). (4) In 6 of 11 patients who underwent resection,
      recurrent elevation of CA 19-9 preceded changes detectable by computed tomography
      or clinical examination by 2 to 9 months. (5) In 23 patients who died of
      pancreatic carcinoma, 15 (65%) had an obvious rise in CA 19-9 level before death.
      There was a correlation between the doubling time of the CA 19-9 serum level and
      survival time (r = 0.5, p less than 0.05). Because it can be demonstrated that
      the reduction of tumor burden by resection lowers serum CA 19-9 levels, serum CA
      19-9 levels may be a useful indicator of whether other forms of treatment such as
      radiation therapy or chemotherapy also reduce the tumor burden.

PMID- 1348411
TI  - Angiotensin and adrenoceptors in the hemodynamic response to aortic cross
      clamping.
AB  - This study was designed to test the hypothesis that activation of adrenoceptors
      and/or the renin-angiotensin system plays an important role in the overall
      hemodynamic response to aortic cross-clamping. The experiments were performed on
      anesthetized rats pretreated with either saline (control group), an angiotensin
      converting enzyme inhibitor (enalapril maleate, 2 mg/kg), an alpha 1-adrenergic
      antagonist (prazosin hydrochloride, 0.5 mg/kg), a beta-adrenergic antagonist
      (propranolol hydrochloride, 5 mg/kg), or an alpha 2-adrenergic antagonist
      (atipamezole, 5 mg/kg). Cross-clamping of the thoracic aorta was associated with
      an expected increase in mean arterial pressure and systemic vascular resistance
      in all animals. During the period of cross-clamping, cardiac output gradually
      decreased in all groups. Animals pretreated with the alpha 1-adrenergic
      antagonist or the angiotensin-converting enzyme inhibitor developed hypertension
      of a lesser degree than the control animals, while rats pretreated with the beta
      adrenergic or alpha 2-adrenergic antagonist demonstrated a greater arterial
      hypertension than the control animals. The possible mechanisms underlying the
      observed differences are discussed. In conclusion, the present study confirms the
      posed hypothesis that the reninangiotensin and sympathetic nervous systems play
      an important role in hemodynamic response to cross-clamping of the thoracic
      aorta.

PMID- 1348412
TI  - Inflammatory mediators, infection, sepsis, and multiple organ failure after
      severe trauma.
AB  - The relation of (multiple) organ failure (OF) to the release of inflammatory
      mediators and the incidence of infection and sepsis was studied prospectively in
      100 patients with multiple trauma (injury severity score = 37). Sixteen patients
      died of OF, 47 patients survived OF, and 37 patients had no OF. Fifteen (24%) of
      the patients with OF showed no signs of infection. In patients with early onset
      of OF (n=45), infection followed with a lag of 2 or more days. In 16 (44%) of
      these patients, infection led to a deterioration in organ function. With late
      onset of OF (n=18), infection preceded OF in nine patients. Polymorphonuclear
      leukocyte-elastase, neopterin, C-reactive protein, lactate, antithrombin III, and
      phospholipase A discriminated significantly among the three outcome groups. Of
      all factors, only polymorphonuclear leukocyte-elastase showed a difference
      between patients with and without infection or sepsis, respectively. These data
      indicate that infection might not play a crucial role in the pathogenesis of
      posttraumatic OF in a substantial portion of patients with trauma. Early OF,
      especially, seems to be mainly influenced by the direct sequelae of tissue damage
      and shock (eg, the release of inflammatory mediators). Since infection and sepsis
      did not lead to an augmented release of mediators in patients with trauma, the
      role of both entities remains unclear.

PMID- 1348413
TI  - Do NMDA antagonists prevent neuronal injury? No.

PMID- 1348414
TI  - Excitatory amino acids in cerebrospinal fluid in neonatal asphyxia.
AB  - Of the excitatory amino acids, glutamic and aspartic acid were studied in the
      cerebrospinal fluid of six infants 4-32 hours after a documented episode of
      severe neonatal asphyxia. Aspartic acid concentration was definitely increased in
      the cerebrospinal fluid of these patients, whereas glutamic acid concentration
      varied considerably. Aspartic acid was always increased, even hours after the
      period of asphyxia, but values were greater in samples taken less than 12 hours
      after the asphyxial event. The patients with the highest cerebrospinal fluid
      aspartic acid concentrations had more severe outcomes.

PMID- 1348416
TI  - Bacteriuria in men infected with HIV-1 is related to their immune status (CD4+
      cell count).
AB  - OBJECTIVE: Reports from the United States that urinary tract infections (UTI) are
      more common in homosexual than in heterosexual men have not been confirmed in
      Europe. The occurrence of several UTI in men infected with HIV-1 has been
      recorded in The Netherlands. We therefore analysed the relationship between the
      presence of bacteriuria and the immune status (CD4+ cell count) in these HIV-1
      infected patients. DESIGN: Urinary cultures were obtained prospectively for 2
      years, during the first visit and every 6 months thereafter, when signs and
      symptoms of UTI occurred and when patients had fever of unknown origin. CD4+ cell
      counts were measured at the same time. SETTING: The study was performed at the
      University Hospital, Utrecht, The Netherlands. PATIENTS, PARTICIPANTS: One
      hundred and thirty HIV-1-infected men attended our hospital. Data from 98 were
      analysed. Eighty-nine (91%) of these men were either homo- or bisexual. MAIN
      OUTCOME MEASURES: Positive urinary culture. RESULTS: Group 1 (CD4+ cell count
      less than 200 x 10(6)/l) consisted of 47 patients; 30% had at least one period of
      bacteriuria, with 21 episodes. Group 2 (CD4+ cell count 200-500 x 10(6)/l)
      consisted of 27 patients; 11% had at least one period of bacteriuria, with five
      episodes. We did not find bacteriuria in the 24 patients in group 3 (CD4+ cell
      count greater than 500 x 10(6)/l). The rate of bacteriuria per patient-month, 4
      (group 1) versus 2 (group 2), differed significantly (P less than 0.001). A
      significant relationship between CD4+ cell count and bacteriuria was found (P =
      0.00003); no relationship, however, was found with anal intercourse,
      hospitalization, Karnofsky score, follow-up, or age. CONCLUSION: We conclude that
      men infected with HIV and presenting with a CD4+ cell count less than 200 x
      10(6)/l are at increased risk for bacteriuria.

PMID- 1348415
TI  - Expression of intercellular adhesion molecule-1 in thyroid follicular cells in
      autoimmune, non-autoimmune and neoplastic diseases of the thyroid gland:
      discordance with HLA.
AB  - The presence of intercellular adhesion molecule-1 (ICAM-1) on epithelial cells
      facilitates their recognition by specific T lymphocytes. To assess the possible
      role of ICAM-1 in the recognition of thyroid follicular cells by T cells in
      thyroid autoimmune disease, we investigated the expression of ICAM-1 in
      thyrocytes from thyroid glands affected by Graves' disease, in glands with non
      autoimmune pathology and normal glands using immunofluorescence staining on
      cryostat sections and on dispersed cell preparations. Sequential tissue sections
      from glands affected by Graves' disease (n = 15), multinodular goitre (MNG, n =
      26), benign nodules (n = 11), primary carcinomas (n = 12) and control thyroid
      glands (n = 5) were stained for ICAM-1, HLA class I, HLA class II, CD3 and
      thyroid peroxidase (TPO). Weak and patchy ICAM-1 expression was found in the
      thyrocytes of 4/15 (27%) Graves' disease and of 1/26 (4%) multinodular goitre
      glands. In contrast, ICAM-1 expression was detected in the thyrocytes of 5/11
      (45%) benign nodules and of 8/12 (67%) thyroid carcinomas in which it was
      sometimes strong. Thyrocytes in the five control glands were negative. These
      results correlated well with flow cytometry data from 23 of these glands which
      showed that ICAM-1 expression in thyrocytes from Graves' patients was, when
      present, 'dull', while in some malignant thyrocytes it was 'bright'. In
      preparations of thyrocytes from Graves' disease glands we found a striking
      discordance between the high levels of expression of HLA class I and HLA class II
      and the low expression of ICAM-1. This is surprising since in vitro the
      expression of these three molecules is equally induced by IFN-gamma and TNF
      alpha. These results suggest that additional factors are involved in the
      induction of the inappropriate HLA class II expression observed in the thyrocytes
      of glands affected by Graves' disease.

PMID- 1348418
TI  - Use of monitored CD4 cell counts: predictions of the AIDS epidemic in Scotland:
      CD4 Collaborative Group.
AB  - OBJECTIVE: We describe the CD4 database of the Scottish Immunology Laboratories,
      and its uses and limitations for making short-term predictions of a CD4 cell
      count less than or equal to 200 x 10(6)/l (CD4(200)) and of adult AIDS cases in
      Scotland. DESIGN: The date of the earlier of two consecutive samples (typically 3
      months apart) both with CD4 cell counts less than or equal to 200 x 10(6)/l was
      taken to define when a patient had passed the CD4(200) threshold (referred to as
      a CD4(200) case). The CD4 database comprises HIV-1-seropositive adults in the
      four main risk groups [homosexual/bisexual (1), injecting drug users (IDU; 2),
      heterosexual contact (3), and undetermined (9)] from Scotland's three principal
      areas of population (Lothian, Tayside and Strathclyde) who have had a CD4 cell
      count of less than or equal to 500 x 10(6)/l. SETTING: Three hospitals in
      Scotland, the Communicable Diseases (Scotland Unit) and the Medical Research
      Council Biostatistics Unit, Cambridge, UK. PATIENTS, PARTICIPANTS: The CD4
      database at 31 December 1990 listed 813 patients (of whom 52% were IDU): 390 were
      CD4(200)/AIDS cases (of whom 44% were IDU) and 192 were AIDS cases (of whom 32%
      were IDU). RESULTS: Individuals in risk groups 1, 2 and 3 were nearly equally
      represented among newly diagnosed HIV-1 infections in 1990. However, among
      patients with moderate immunodeficiency, IDU accounted for 50% of the total
      number. Co-incidence of first CD4 cell count with CD4(200) diagnosis was recorded
      for only 28% of IDU, but in over 50% of cases for each of the other exposure
      groups (57%). There was a highly significant decrease of around 80 x 10(6)/l per
      calendar-year-of-referral in first CD4 cell counts for patients on the CD4
      database; and decreases of around 40 x 10(6)/lper decade of age at referral.
      Since 1988, median time from CD4(200) to AIDS diagnosis in Scotland has been
      approximately 2 years. Back-projection was applied to annual CD4(200)/AIDS
      diagnoses before 31 December 1990 and to AIDS diagnoses. From AIDS diagnoses, the
      central epidemic scenario underestimated past HIV-1-antibody-positive reports (up
      to the end of 1985). More dramatic underestimation was occasioned by back
      projection from CD4(200)/AIDS diagnoses [319 inferred HIV infections compared
      with 445 HIV-1-antibody-positive reports to Communicable Diseases (Scotland)
      Unit]. CONCLUSIONS: First CD4 cell counts should complement new HIV-1 diagnoses.
      Past referrals for immunological monitoring were not uniform between risk groups
      in Scotland. Underascertainment of CD4(200) cases is a problem when CD4(200)
      cases are used as a basis for back-projection. More information concerning the
      incubation distribution from HIV seroconversion to CD4(200) diagnosis is
      required. It is likely that there are twice as many CD4(200)/AIDS as there are
      diagnosed cases of AIDS.

PMID- 1348417
TI  - Primary prophylaxis with fluconazole against systemic fungal infections in HIV
      positive patients.
AB  - OBJECTIVE: To investigate the efficacy of fluconazole prophylaxis against
      systemic fungal infections in HIV-positive patients. DESIGN: Open label treatment
      compared with historical controls. SETTING: Patients were seen at the Parkland
      Memorial Hospital HIV Clinic, Dallas, Texas, USA between 1 March 1990 and 28
      February 1991. PATIENTS, PARTICIPANTS: Three hundred and thirty-seven historical
      controls were followed for 157 patient-years, and 329 fluconazole-treated
      patients for 145 patient-years. INTERVENTIONS: Fluconazole (100 mg daily) was
      administered to all patients with CD4 lymphocyte counts less than 68 x 10(6)/l
      seen at our HIV clinic after 1 March 1990. MAIN OUTCOME MEASURES: Lysis
      centrifugation blood cultures were recorded monthly for all patients during both
      study periods. RESULTS: Twenty infections (16 cryptococcosis, four
      histoplasmosis) occurred in 337 historical reference control patients (product
      limit 1-year incidence, 7.5 +/- 2.0/year). Four infections (one cryptococcosis,
      three histoplasmosis) occurred in the treated patient group (product-limit 1-year
      incidence, 1.8 +/- 0.9/year). CONCLUSIONS: Fluconazole warrants further
      evaluation for prophylaxis against systemic fungal infections in HIV-positive
      patients.

PMID- 1348419
TI  - Neurotransmitter-mediated inhibition of post-mortem human brain adenylyl cyclase.
AB  - The effects of a range of neurotransmitter agonists showing selectivity for
      receptor types inhibitorily coupled to adenylyl cyclase were compared in membrane
      preparations of hippocampus, frontal cortex and caudate nucleus/striatum from
      previously frozen post-mortem human and rat brain. Agonists were tested against
      basal and forskolin stimulated activities, forskolin being a potent activator of
      the catalytic sub-unit of the enzyme. Of those agonists tested, only somatostatin
      (100 microM) and neuropeptide Y (10 microM) gave consistent inhibitions of basal
      and forskolin stimulated enzyme activities in all three regions of both human and
      rat brain. Somatostatin-mediated inhibition of human brain adenylyl cyclase was
      reduced in the absence of GTP and in the presence of the guanine nucleotide
      partial agonist, guanosine 5'-O-thiodiposphate, consistent with a G-protein
      linked receptor. No such GTP-dependence was found for the neuropeptide Y-mediated
      adenylyl cyclase inhibition. GTP-dependent somatostatin mediated inhibitions of
      human brain adenylyl cyclase activity were of highest magnitude in the thalamus,
      intermediate magnitude in the hippocampus and caudate nucleus and lowest
      magnitude in the frontal cortex. It is concluded that of a range of
      neurotransmitter receptor agonists tested, only somatostatin gives robust, GTP
      dependent responses that are reproducible enough to be used with post-mortem
      tissue for the comparison of receptor function in human brain disorders.

PMID- 1348420
TI  - A rapid assay for neurotransmitter amino acids, aspartate, glutamate, glycine,
      taurine and gamma-aminobutyric acid in the brain by high-performance liquid
      chromatography with electrochemical detection.
AB  - For simultaneous assay of the five neurotransmitter amino acids, Asp, Glu, Gly,
      Tau, and GABA in brain tissues, a very rapid and simple chromatographic method
      using high-performance liquid chromatography with electrochemical detection in
      combination with o-phthalaldehyde derivatization is described. Because the
      present method permits the determination of these five amino acids within less
      than five minutes in one chromatographic run, up to 100 samples a working day can
      be analyzed using an autosampler. Within-run coefficients of variation for these
      five amino acids were less than 2% (n = 20). The quantitative detection limit was
      2.5 pmol for the 5 amino acids. The present method has been applied to the
      measurement of the five amino acid neurotransmitter levels in several discrete
      brain regions of mice treated with and without electroconvulsive shock.

PMID- 1348421
TI  - Involvement of 5-HT1B receptors in the anticonflict effect of m-CPP in rats.
AB  - The anticonflict activity of m-CPP, a non-selective agonist of 5-HT receptors,
      was studied in the drinking conflict test in rats. m-CPP administered in doses of
      0.125-0.5 mg/kg increased the number of punished licks, the maximum effect having
      been observed after a dose of 0.25 mg/kg. The anticonflict effect of m-CPP (0.25
      mg/kg) was antagonized by the non-selective 5-HT antagonist metergoline (1-4
      mg/kg) and by the beta-adrenoceptor blocker SDZ 21009 (2 and 4 mg/kg) with
      affinity for 5-HT1A and 5-HT1B receptors. On the other hand, the 5-HT1A receptor
      antagonist NAN-190 (0.5 and 1 mg/kg), the 5-HT2 receptor antagonist ritanserin
      (0.25 and 0.5 mg/kg), and the beta-blockers betaxolol (8 mg/kg) and ICI 118,551
      (8 mg/kg) with no affinity for 5-HT receptors did not affect the effect of m-CPP.
      The effect of m-CPP was not modified, either, in animals with the 5-HT lesion
      produced by p-chloroamphetamine. These results suggest that the anticonflict
      effect of m-CPP described above results from stimulation of 5-HT1B receptors-
      most probably these which are located postsynaptically.

PMID- 1348422
TI  - Care of the older cancer patient: clinical and quality of life issues.
      Proceedings of the Second Quality of Life Symposium. Long Beach, California,
      February 23-24, 1991.

PMID- 1348423
TI  - Genetic evidence that placental site trophoblastic tumours can originate from a
      hydatidiform mole or a normal conceptus.
AB  - The genetic origin of two placental site trophoblastic tumours was established
      using a Y chromosome-specific and locus-specific minisatellite probes. A
      gestational origin was confirmed for both tumours. In one case the origin of the
      tumour was consistent with derivation from a normal female conceptus while the
      other was shown to arise from a homozygous complete hydatidiform mole, an
      abnormal conceptus more usually associated with the development of
      choriocarcinoma.

PMID- 1348425
TI  - Levels of expression of the mdr1 gene and glutathione S-transferase genes 2 and 3
      and response to chemotherapy in multiple myeloma.
AB  - We have quantitated the levels of mRNAs in bone marrow samples from patients with
      multiple myeloma of the mdr1 gene (responsible for the Multidrug Resistance
      phenotype) and for two of the glutathione S-transferase gene, GST-2 and GST-3
      (which can also inactivate a wide variety of cytotoxic drugs) and examined the
      relationship between the levels of expression of these genes and response to
      subsequent chemotherapy. From a total of 47 patients, 37 were treated with
      chemotherapy with 34 evaluable for response. Twenty-nine of the patients treated
      had not received any treatment prior to the marrow sampling while eight had
      previously received chemotherapy. Patients who failed to respond to initial
      chemotherapy had significantly higher levels of mdr1 than patients who responded
      (P = 0.01). In the total myeloma patient data set, mRNA levels for mdr1 and GST-2
      were significantly correlated (Spearman rank correlation coefficient (r) = 0.54,
      P = 0.0004) as were expression levels of GST-2 with GST-3 (r = 0.43, P = 0.017).
      GST-3 and mdr1 levels were more weekly associated (r = 0.16, P = 0.4). These data
      would suggest a significant relationship between failure of chemotherapy in
      multiple myeloma patients and increases in expression of the mdr1 gene together
      with other genes whose products will generate additional mechanisms of resistance
      to chemotherapeutic agents.

PMID- 1348424
TI  - Predicting outcome for patients with node negative breast cancer: a comparative
      study of the value of flow cytometry and cell image analysis for determination of
      DNA ploidy.
AB  - This study was aimed at determining whether tumour DNA content measured by cell
      image analysis could provide additional prognostic information when compared to
      that provided by flow cytometry. Sections cut from paraffin blocks of tumours
      from 101 patients with node negative breast cancer were analysed by both methods
      and the results related to other prognostic variables and to patient relapse and
      overall survival. DNA ploidy measured by flow cytometry classified 46 tumours as
      diploid and 55 as aneuploid, whereas by cell image analysis 30 were diploid and
      71 aneuploid (P less than 0.002). There were 20 tumours with discrepancies
      between the two methods; 18 of these were tumours with only one peak in flow
      analysis, but determined to be aneuploid with image analysis. DNA content as
      measured by both methods was significant for predicting relapse and survival by
      log-rank test, as were tumour histological grade, c-erbB-2 expression and tumour
      size. Multivariate analysis showed DNA ploidy measured by flow cytometry to be
      the only variable of independent significance (P less than 0.02) for both relapse
      and overall survival. Compared with cell image analysis, flow cytometry
      demonstrated a significantly higher proportion of diploid tumours, which may be
      related to differences in the internal standards applied to each method. We
      suggest that cell image analysis techniques can provide more sensitive
      information on the DNA content of tumour cells by direct measurement of nuclear
      DNA density of both normal lymphocytes and tumour cells in the same section.
      However, although image analysis appears to be more sensitive than flow cytometry
      in detecting DNA aneuploidy, the image technique appears to lack the specificity
      of flow cytometry in correlation with clinical outcome.

PMID- 1348426
TI  - GABA inhibits ACh release from the rabbit retina: a direct effect or feedback to
      bipolar cells?
AB  - The cholinergic amacrine cells of the rabbit retina may be labeled with [3H]-Ch
      and the activity of the cholinergic population monitored by following the release
      of [3H]-ACh. We have tested the effect of muscimol, a potent GABAA agonist, on
      (1) the light-evoked release of ACh, presumably mediated via bipolar cells, which
      are known to have a direct input to the cholinergic amacrine cells and (2) ACh
      release produced by exogenous glutamate analogs that probably have a direct
      effect on cholinergic amacrine cells. Muscimol blocked the light-evoked release
      of ACh with an IC50 of 1.0 microM. In contrast, ACh release produced by
      nonsaturating doses of kainate or NMDA was not reduced even by 100 microM
      muscimol. Thus, we have been unable to demonstrate a direct effect of GABA on the
      cholinergic amacrine cells. GABA antagonists, such as picrotoxin, caused a large
      increase in the base release and potentiated the light-evoked release of ACh.
      Both these effects were abolished by DNQX, a kainate antagonist that blocks the
      input to cholinergic amacine cells from bipolar cells. DNQX blocked the effects
      of picrotoxin even when controls showed that the mechanism of ACh release was
      still functional. Together, these results imply that the dominant site for the
      GABA-mediated inhibition of ACh release is on the bipolar cell input to the
      cholinergic amacrine cells. This is consistent with previous anatomical and
      physiological evidence that bipolar cells receive negative feedback from GABA
      amacrine cells.

PMID- 1348427
TI  - Structure of the murine tissue factor gene. Chromosome location and conservation
      of regulatory elements in the promoter.
AB  - Tissue factor (TF) is a transmembrane glycoprotein that mediates cellular
      initiation of the coagulation serine protease cascades. Moreover, expression of
      TF in human atherosclerotic plaques is likely to play a significant role in the
      thrombotic complications associated with plaque rupture. In this study the
      complete murine TF gene, Cf-3, was isolated from mouse NIH 3T3 cells and was
      found to consist of six exons spanning about 11 kilobase pairs (kbp) of DNA. A
      major transcriptional start site was located 24 bp downstream of a TATA box. Cf-3
      was mapped to chromosome 3 by analysis of an intersubspecies test cross.
      Conserved transcription factor-binding sites were identified by comparison of 5'
      flanking regions of the murine and human TF genes. A region of the TF promoter
      required for constitutive expression exhibited 85% identity in DNA sequence and
      included two conserved binding sites for Sp1. Furthermore, two AP-1 sites and an
      NF-kappa B site were conserved in a 56-bp region necessary for transcriptional
      activation in response to bacterial lipopolysaccharide. These highly conserved
      regions of the TF promoter, which contain several binding sites for well
      characterized transcription factors, are likely to be functionally important in
      the complex pattern of TF gene expression observed in a variety of cell types.

PMID- 1348428
TI  - Alterations in acetyl coenzyme A carboxylase activities in voles and mice treated
      with monosodium aspartate.
AB  - Changes of body weights and hepatic acetyl-CoA carboxylase activities were
      measured in voles and mice treated with monosodium-L-aspartate (MSA). MSA was
      administrated subcutaneously to neonates at 4 mg/g. The MSA-treated mice showed
      remarkable obesity, associated with the increase in the plasma insulin
      concentrations and acetyl-CoA carboxylase activities. The activity of acetyl-CoA
      carboxylase of control voles was very low; under half that of mice. In the MSA
      treated voles, although the plasma insulin concentrations also increased, acetyl
      CoA carboxylase activities were not elevated and signs of obesity were not
      observed.

PMID- 1348429
TI  - Does modulation of glutamatergic function represent a viable therapeutic strategy
      in Alzheimer's disease?
AB  - Although glutamate dysfunction has been implicated in the pathogenesis of
      Alzheimer's disease (AD), it is unclear which direction a glutamatergic strategy
      should take in this illness. Increasing glutamate function may enhance
      excitotoxicity and neuronal death, whereas decreasing activity in this excitatory
      amino acid pathway may impair memory processes. Pharmacological modulation of the
      different NMDA and nonNMDA receptor sites, together with the concept of an
      agonist versus antagonist approach, are discussed in this review. It would appear
      that a glutamatergic approach may represent a new and exciting option to pursue
      in the experimental pharmacotherapeutics of AD.

PMID- 1348430
TI  - Plasma homovanillic acid, plasma anti-D1 and -D2 dopamine-receptor activity, and
      negative symptoms in chronically mediated schizophrenia.
AB  - We have investigated the relationship between the concentration of homovanillic
      acid in human plasma (pHVA) and plasma anti-D1 and anti-D2 dopamine receptor
      activity in chronic schizophrenic patients whose neuroleptic dosage was changed.
      The change in pHVA level correlated with that in anti-D1, not anti-D2 activity,
      thus suggesting that the neuroleptic-induced changes in pHVA concentration may be
      associated with the blocking of D1- as well as D2- receptors. The change of
      scores on the Scale for the Assessment of Negative Symptoms did not significantly
      correlate with changes in anti-D1 or anti-D2 activity, but did so correlated with
      the change in pHVA level.

PMID- 1348431
TI  - Electroconvulsive therapy for persistent neuroleptic-induced akathisia and
      parkinsonism: a case report.
AB  - Neuroleptic-induced akathisia (NIA) and parkinsonism (NIP) continued for 3
      months, despite two courses of anticholinergic treatments, a shift to low-potent
      neuroleptic (NL) and a NL-free period. The two adverse effects responded
      dramatically to electroconvulsive therapy (ECT) to reemerge 3 months after
      termination of ECT. The case supports the idea that ECT is effective for both NIA
      and NIP even when they are resistant.

PMID- 1348432
TI  - Integrin expression profiles during erythroid differentiation.
AB  - To study the expression of integrins at the erythroid progenitor level we
      isolated selected populations of cells from human fetal liver after
      immunoadherence to anti-beta 2 integrin (CD18) coated plates. These CD18 adherent
      cells (CD18-Ad), in contrast to CD18 nonadherent cells (CD18-NAd), have a
      blastlike cell morphology and are highly enriched in all progenitor types (14% to
      37% progenitors). By several criteria progenitor cells present in CD18-Ad cells
      appear to have a higher proliferative potential and diversity than the ones found
      in CD18-NAd, which were mostly later erythroid progenitors. Positivity of CD18-Ad
      cells with the common beta 2 integrin (CD18) is largely attributable to
      expression of alpha L (CD11a) chain, rather than alpha M (CD11b). CD11a is
      present in all types of progenitors, but it is selectively lost at later stages
      of erythroid differentiation/maturation. By contrast, CD11b appears to be
      virtually absent from all progenitors but it has an enhanced expression during
      granulomonocytic differentiation/maturation. In addition to beta 2 integrins,
      CD18-Ad cells express several other cytoadhesion molecules (VLA-4, VLA-5, I-CAM,
      H-CAM) as well as other progenitor cell antigens (CD34, HLA-DR, CD38). Cells
      expressing all these antigens were selectively enriched in CD18-Ad cells. Our
      data add new information on the regulation of CD11a and CD11b molecules in
      hematopoiesis and on the composite profile of integrin expression at several
      stages of erythroid differentiation.

PMID- 1348433
TI  - Different molecular consequences of the 1;19 chromosomal translocation in
      childhood B-cell precursor acute lymphoblastic leukemia.
AB  - The prognostically important 1;19 chromosomal translocation can alter the E2A
      gene on chromosome 19p13 in childhood B-cell precursor acute lymphoblastic
      leukemia (ALL), leading to formation of a fusion gene (E2A-PBX1) that encodes a
      hybrid transcription factor with oncogenic potential. It is not known whether
      this molecular alteration is a uniform consequence of the t(1;19) or is
      restricted to translocation events within specific immunologic subtypes of the
      disease. Therefore, we studied leukemic cells from 25 cases of B-cell precursor
      ALL, with or without evidence of cytoplasmic Ig mu heavy chains (cIg); 17 cases
      had the t(1;19) by cytogenetic analysis. Leukemic cell DNA samples were analyzed
      by Southern blotting to detect alterations within the E2A genomic locus; a
      polymerase chain reaction assay was used to identify expression of chimeric E2A
      pbx1 transcripts in leukemic cell RNA; and immunoblotting with anti-Pbx1
      antibodies was used to detect hybrid E2A-Pbx1 proteins. Of 11 cases of cIg+ ALL
      with the t(1;19), 10 had E2A-pbx1 chimeric transcripts with identical junctions
      and a characteristic set of E2A-Pbx1 hybrid proteins. Each of these cases had E2A
      gene rearrangements, including the one in which fusion transcripts were not
      detected. By contrast, none of the six cases of t(1;19)-positive, cIg- ALL had
      evidence of rearranged E2A genomic restriction fragments, detectable E2A-pbx1
      chimeric transcripts, or hybrid E2A-Pbx1 proteins. Typical chimeric E2A-pbx1
      transcripts and proteins were detected in one of eight cIg+ leukemias in which
      the t(1;19) was not identified by cytogenetic analysis, emphasizing the increased
      sensitivity of molecular analysis for detection of this abnormality. We conclude
      that the molecular breakpoints in cases of cIg- B-cell precursor ALL with the
      t(1;19) differ from those in cIg+ cases with this translocation. Leukemias that
      express hybrid oncoproteins such as E2A-Pbx1 or Bcr-Abl have had a poor prognosis
      in most studies. Thus, molecular techniques to detect fusion genes and their
      aberrant products should allow more timely and appropriate treatment of these
      aggressive subtypes of the disease.

PMID- 1348435
TI  - Dendrocytes in verruga peruana and bacillary angiomatosis.
AB  - Verruga peruana and bacillary angiomatosis are two cutaneous diseases
      characterized by angiomatous growths linked to the presence of rickettsia-like
      organisms. These lesions are currently considered to be endothelial hyperplasias
      and to share many features. By immunohistochemistry and computerized image
      analysis, we studied the presence of factor-XIIIa-positive dendrocytes in these
      lesions and compared our data with similar research in capillary angiomas and
      normal skin. Other cell lines were studied by Ulex europaeus and by antibodies to
      the L1 antigen and to the von Willebrand factor. Dendrocytes were identified in
      the three types of angiomatous growth. They were numerous and appeared plump, but
      no more dendritic than in normal skin. Verruga peruana and bacillary angiomatosis
      should therefore be viewed as combined growths of endothelial cells and
      dendrocytes. The biological link between these two types of cells is emphasized.

PMID- 1348434
TI  - Transplantation of umbilical cord blood after myeloablative therapy: analysis of
      engraftment.
AB  - The possibility that umbilical cord and placental blood from an HLA-identical
      sibling might produce stable donor-derived lymphohematopoietic engraftment was
      tested in a patient with juvenile chronic myelogenous leukemia (JCML). After
      conditioning with high-dose busulfan and cyclophosphamide, cryopreserved
      umbilical cord blood, containing 0.5 x 10(8) nucleated cells/kg and 2.7 x 10(4)
      colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A
      leukocyte count greater than 1,000/microL, absolute neutrophil count (ANC)
      greater than 500/microL, and platelet count greater than 20,000/microL
      (untransfused) were observed on days 39, 39, and 47 after transplantation,
      respectively. Donor cell engraftment was documented in the peripheral blood and
      bone marrow by cytogenetic analysis, restriction fragment length polymorphism
      (RFLP), and polymerase chain reaction (PCR) as early as day 21. Furthermore, the
      donor origin of each lymphohematopoietic lineage (ie, CD5+ T cells, CD19/20+ B
      cells, CFU-GM, and burst-forming unit-erythrocyte [BFU-E]) was confirmed. On day
      200, assays of the peripheral blood and bone marrow showed an abnormal
      proliferation of CFU-GM at low seeding densities in the absence of exogenous
      growth factors, as well as a hypersensitivity to granulocyte-macrophage colony
      stimulating factor (GM-CSF), both pathophysiologic characteristics of JCML.
      Recurrent disease was confirmed histologically on day 225. Together, these
      results demonstrate that umbilical cord blood contains sufficient numbers of
      hematopoietic stem cells necessary for the engraftment of leukemia patients
      treated with myeloablative therapy and that the detection of "spontaneous" CFU-GM
      and hypersensitivity to GM-CSF after treatment is a marker of residual or
      recurrent disease in patients with JCML.

PMID- 1348436
TI  - Restriction fragment length polymorphisms associated with alpha-hemolysin
      determinants are correlating with the expression of alpha-hemolysin in strains of
      Escherichia coli.
AB  - Three different phenotypes of hemolysis on blood-agar were detected when 58
      isolates of Escherichia coli were investigated for alpha-hemolysin synthesis. In
      strains with chromosomally encoded alpha-hly genes, phenotype I (large and clear
      hemolysis zones) corresponded with high hemolytic activity and with a 17.2 kb
      size BamHI restriction fragment hybridizing with an alpha-hly-specific gene
      probe. Phenotype II (small and turbid hemolysis zones) was associated with low
      hemolytic activity and generally with a 12.8 kb size hybridizing BamHI
      restriction fragment. An intermediate phenotype (type I/II) was found in a few
      strains with moderate hemolytic activity. This correlation between hemolytic
      phenotype and activity was not found in E. coli carrying alpha-hly plasmids. Type
      I strains differed from all others in the promotor region of their 17.2 kb size
      BamHI fragment associated chromosomal alpha-hly determinant. The relation between
      hemolytic phenotype and DNA hybridization pattern was found in unrelated E. coli
      isolates of human and animal origin. An association of alpha-hemolysin with other
      virulence factors was found in most strains of all three phenotypes.

PMID- 1348437
TI  - Adhesion of fimbriated and non-fimbriated Klebsiella strains to synthetic
      polymers.
AB  - Adherence of three fimbriated and non-fimbriated Klebsiella strains to
      polyetherurethane was investigated in order to assess the possible role of
      fimbriae in the adhesion of Klebsiella to synthetic polymers. Fimbriated strains
      with type 1 and type 1.3 fimbriae adhere significantly stronger to polyurethane
      than the same strains lacking fimbriae, whereas a strain with type 3 fimbriae
      shows no different adherence compared with the non-fimbriated variant. Analysis
      of adhesion kinetics and isotherms reveals that adherence of fimbriated
      Klebsiella strains is proceeded by the formation of multicellular bacterial
      layers on the polymer surface. Measurements of the relative hydrophobicity of the
      strains and adherence experiments under exclusion of unspecific interactions
      point out that fimbriae obviously play a more important role in adhesion than
      relative hydrophobicity. The demonstration of reduction of bacterial adherence to
      polyetherurethane by blocking fimbrial action with fimbriae-specific sugars
      supports this further.

PMID- 1348438
TI  - Restriction fragment length polymorphism and virulence pattern of the veterinary
      pathogen Escherichia coli O139:K82:H1.
AB  - Escherichia coli O139:K82:H1 strains originating from outbreaks and single cases
      of oedema disease in pigs were characterized by their genomic restriction
      fragment length polymorphism (RFLP), their virulence pattern, and by the
      occurrence as well as the genomic distribution of the determinants for hemolysin
      (hly) and verotoxins (shiga-like toxins; sltI, sltII). Whereas the RFLPs revealed
      considerable variation among the E. coli O139:K82:H1 isolates depending the
      origin and epidemic source of the strains, the virulence gene slt II was found to
      be present in nearly all strains in a particular chromosomal region. Similar to
      RFLPs, the plasmid profiles are useful for epidemiological analysis.

PMID- 1348439
TI  - Determination of S fimbriae among Escherichia coli strains from extraintestinal
      infections by colony hybridization and dot enzyme immunoassay.
AB  - 449 E. coli strains obtained from septic infections (124 isolates), urinary tract
      infections (246) and water (79) were surveyed for S/F1C fimbrial DNA by DNA
      hybridization and for expression of S fimbriae by enzyme immunoassay. S/F1C
      fimbrial DNA was detected with greater frequency in septic (35%) and urinary
      (43%) isolates than in water isolates and was often associated with the O2, O4,
      O6, O18, O83, and O156 serogroups. Most O45 strains did not possess such
      sequences. Only 12% and 28%, respectively, of the septic and urinary strains
      possessing S/F1C fimbrial DNA expressed S fimbriae.

PMID- 1348440
TI  - Treatment of hypertension in older adults.

PMID- 1348442
TI  - A search for contrast effects with fear evoking stimuli.
AB  - The occurrence of fear contrast effects was investigated in a laboratory study of
      fearful people. A total of 65 university students were exposed on separate
      occasions to two fearful stimuli (spiders and snakes). The first exposure session
      was manipulated so that experimental groups differed in the amount of fear evoked
      by the stimulus (high fear, moderate fear and low fear). Exposure to the second
      animal was designed to produce a moderate level of fear in all subjects. During
      exposure to the animals, measures of subjective fear and heart rate were taken.
      Compared to a control group of subjects who experienced moderate fear on two
      occasions, a prior high fear experience led to a decrease in fear of the second
      stimulus, and a prior low fear experience led to an increase in fear of the
      second stimulus. The increase in fear in the latter group was evident in both
      subjective and physiological indices of fear, but in the high fear group the
      contrast was evident only in subjective fear.

PMID- 1348441
TI  - High purity factor VIII concentrates and HIV infection.

PMID- 1348444
TI  - The electrical and mechanical responses of the rabbit saphenous artery to nerve
      stimulation and drugs.
AB  - 1. Electrical and mechanical responses to field stimulation (1-64 Hz, 0.5 ms
      supramaximal voltage) were recorded simultaneously in the rabbit saphenous
      artery. The electrical response consisted entirely of excitatory junction
      potentials (e.j.ps) which were abolished by alpha, beta methylene ATP (alpha,
      beta MeATP, 10(-6) M) and by tetrodotoxin (TTX, 10(-6) M) but were unaffected by
      the alpha 1-adrenoceptor antagonist, prazosin (10(-6) M). No additional
      electrical response was evoked by field stimulation, even in the presence of
      normetanephrine (NMN) and desmethylimipramine (DMI, each 10(-6) M), which block
      neuronal and extraneuronal uptake of noradrenaline (NA) respectively. Action
      potentials to field stimulation were produced only in the presence of
      tetraethylammonium (10(-3) M) which also enhanced the contraction. 2.
      Contractions to field stimulation were reduced (by some 50%) by prazosin (10(-6)
      M) and abolished by the additional presence of alpha, beta MeATP (10(-6) M),
      which blocks purinoceptors by desensitization, suggesting the involvement of both
      NA and an ATP-like substance in the contractile response. 3. Idazoxan (10(-6) M)
      which blocks prejunctional alpha 2-adrenoceptors, significantly increased the
      amplitude of both e.j.ps and the contraction to field stimulation (10 pulses, 1-4
      Hz, 0.5 ms, supramaximal voltage). 4. NA (10(-2) M by pressure ejection) did not
      alter membrane potential even in the presence of NMN and DMI (each 10(-6) M). ATP
      (10(-2) M by pressure ejection) produced a concentration-dependent, alpha, beta
      MeATP-sensitive depolarization. 5. In tissues desensitized by constant infusion
      of alpha, beta MeATP (10(-6) M contractions to NA (10(-7) - 3 x 10(-5) M),
      histamine (10(-7) - 3 x 10(-5) M) and KCl (1-1.6 x 10(-2) M) were unaffected.6.
      Following restoration of the membrane potential, after an initial depolarization,
      alpha,beta MeATP (4 x 10-6M) did not change the amplitude of electrotonic
      hyperpolarizing current pulses significantly but abolished evoked ej.ps. The
      rates of recovery of evoked ej.ps and the depolarization to ATP (10-2M by
      pressure ejection) following desensitization to alpha,beta MeATP (10- 6 M) were
      comparable. These results suggest that the effects of a,fl MeATP are mediated
      selectively via receptors (purinoceptors).7. Suramin (10-3M) abolished ej.ps and
      the prazosin (10-6M), insenstive component of the contractile response and
      antagonized contractions to xfl MeATP (10-7_1i-5M), ATP (10-5_1i-3M), histamine
      (10- 7-3 x 10-SM) and 5-hydroxytryptamine (10-7-10-SM) but those to NA (10-7-10
      SM) and KCI (1-1.6 x 10-2 M) were unaffected. Suramin is insufficiently
      selective, under these conditions, as a purinoceptor antagonist.

PMID- 1348443
TI  - Endothelial-dependent sexual dimorphism in vascular smooth muscle: role of Mg2+
      and Na+.
AB  - 1. In isolated aortae of the male rat [Mg2+]o withdrawal and concomitant
      reduction in [Na+]o (to 84 mM) induced significant increases of basal tone, but,
      surprisingly, this did not occur in intact aortae removed from female rats. Such
      tension development, however, was observed in endothelium-denuded aortic
      preparations from both sexes. These observed gender-related differences were not
      dependent on animal strain or types of tissue preparations. 2. No tension
      development was observed in aortae obtained from castrated males treated with
      oestradiol. Aortic tissues of sexually-immature male and female rats exhibited
      marked tension development when exposed to 0 mM [Mg2+]o and low [Na+]o. 3.
      Tension development in Mg(2+)-free, low-Na+ media was not tachyphylactic and
      completely dependent on extracellular Ca2+; addition of 1.2 mM Mg2+ to the Mg2+
      and Na(+)-deficient incubation media relaxed the increase in tension to a normal
      basal level. 4. Two known endothelial-derived relaxant factor (EDRF) inhibitors,
      methylene blue and haemoglobin, induced tension development in female aortae with
      intact endothelium exposed to Mg(2+)-Na+ deficient media, while use of a specific
      inhibitor of EDRF-derived nitric oxide, viz., NG-monomethyl-L-arginine (L-NMMA),
      resulted in potentiation of tension development in male, but not in female,
      aortae. This effect of L-NMMA was antagonized by L-arginine. 5. The Ca ionophore,
      A23187, partially relaxed contractile responses in male aortae (with intact
      endothelium) which were followed by potentiated contractions. Endothelium
      dependent vasodilator responses to A23187 (10(-10)-10(-6) M) of aortic rings from
      male or female rats in normal Krebs-Ringer bicarbonate solution were not
      different.6. These results suggest that: (a) as in vascular smooth muscle cells,
      Mg2+ plays an important role in Ca2 + homeostasis in endothelial cells, probably
      via Na+-Ca2+ exchange; and (b) sex steroid hormones, probably the female sex
      hormone, 17-beta-oestradiol, may regulate contractile responses of intact
      vascular smooth muscle by modifying endothelium functions through such Mg2 '
      regulated internal Natdependent Ca2+ entry. These data may help to explain why
      female subjects, despite Mg deficiency, unlike male subjects, are protected
      against ischaemic heart disease and cerebrovascular disease until menopause.

PMID- 1348445
TI  - Characterization of postsynaptic alpha-adrenoceptors in the arteries supplying
      the oviduct.
AB  - 1. In vitro experiments were designed to characterize postjunctional alpha
      adrenoceptor subtypes in ring segments (1 mm length; outer diameter 300-500
      microns) from arteries supplying the oviduct of the heifer. 2. Noradrenaline,
      adrenaline and phenylephrine evoked concentration-dependent contractile
      responses. The pD2 values were 5.67, 5.89 and 5.93, respectively. Medetomidine
      clonidine and B-HT 920 (2-amino-6-allyl-5,6,7,8-tetra-hydro-4H-(thiazo)-4,5-d
      azepoine ) were ineffective. 3. The alpha-adrenoceptor selective antagonists,
      prazosin (1 nM-0.1 microM) and rauwolscine (0.1-10 microM) competitively
      antagonized the response to noradrenaline. The pA2 values were 9.38 and 6.83,
      respectively. 4. The dissociation constant (KD) for noradrenaline calculated by
      use of the irreversible antagonist, dibenamine, was 3.95 (2.09-5.81) microM. The
      occupancy-response relationship was non-linear. Half-maximal response to
      noradrenaline was obtained with 22% receptor occupancy while maximal response
      required 100% occupancy. 5. B-HT 920 evoked a biphasic contractile concentration
      dependent response in preparations incubated in a physiological solution
      containing 20 mM K+, 0.1 microM prazosin and 1 microM propranolol. Rauwolscine
      0.1 microM significantly (P less than 0.01) blocked the first component of the B
      HT 920 concentration-response curve with an apparent pA2 value of 8.52 (7.86
      9.18). 6. These results strongly suggest that alpha-adrenoceptors in oviductal
      arteries are mainly of the alpha 1 subtype, although a possible role for alpha 2
      adrenoceptors cannot be excluded.

PMID- 1348446
TI  - Reduced alpha 1- and beta 2-adrenoceptor-mediated positive inotropic effects in
      human end-stage heart failure.
AB  - 1. alpha 1-Adrenoceptor (phenylephrine in the presence of propranolol) and beta 2
      adrenoceptor (fenoterol)-mediated positive inotropic effects were investigated in
      human ventricular preparations isolated from five non-failing (prospective organ
      donors) and from eight explanted failing hearts with end-stage idiopathic
      dilative cardiomyopathy (NYHA IV). 2. For comparison, the nonselective beta
      adrenoceptor agonist isoprenaline, the phosphodiesterase (PDE) inhibitor 3
      isobutyl-1-methylxanthine (IBMX), the cardiac glycoside dihydroouabain, and
      calcium were studied. 3. Furthermore, the influence of IBMX on adenosine 3':5'
      cyclic monophosphate (cyclic AMP) PDE activity as well as total beta-adrenoceptor
      density, beta 1- and beta 2-adrenoceptor subtype distribution, and alpha 1
      adrenoceptor density were compared in nonfailing and failing human heart
      preparations. The radioligands (-)-[125I]-iodocyanopindolol for beta-adrenoceptor
      binding and [3H]-prazosin for alpha 1-adrenoceptor binding were used. 4. The
      inotropic responses to calcium and dihydroouabain in failing human hearts were
      unchanged, whereas the maximal alpha 1- and beta 2-adrenoceptor-mediated positive
      inotropic effects were greatly reduced. The inotropic effects of the other cyclic
      AMP increasing compounds, i.e. isoprenaline and IBMX, were also reduced to about
      60% of the effects observed in nonfailing controls. The potency of these
      compounds was decreased by factors 4-10. 5. The basal PDE activity and the PDE
      inhibition by IBMX were similar in nonfailing and failing preparations. 6. The
      total beta-adrenoceptor density in nonfailing hearts was about 70 fmol mg-1
      protein. In failing hearts the total number of beta-adrenoceptors was markedly
      reduced by about 60%. The betal/beta2-adrenoceptor ratio was shifted from about
      80/20% in nonfailing to approximately 60/40% in failing hearts which was due to a
      selective reduction of beta1-adrenoceptors. The beta2-adrenoceptor population
      remaining unchanged. alpha-Adrenoceptor density was increased from about 4 fmol
      mg-' protein in nonfailing to 10 fmol mgprotein in failing hearts.7. Changes in
      PDE activity and adrenoceptor downregulation cannot completely explain the
      reduced positive inotropic effects of alpha 1- and beta 2-adrenoceptor agonists
      in failing human hearts. This supports the hypothesis that impairment of other
      processes such as the coupling between receptor and effector system, i.e. the
      respective G-proteins, are equally important in end-stage heart failure.

PMID- 1348447
TI  - [Localization of two neurotropic molecules in cultured glial cells by ion
      microscopy].
AB  - The intracellular localization of two families of neurotropic drugs:
      flunitrazepam and flurazepam (benzodiazepine), triflupromazine and
      trifluoperazine (phenothiazine) has been studied by ion microscopy. The molecules
      have been incubated with C6 glioblastoma cells from rat origin and with
      astroglial primary cultures. The images of the intracellular distributions of the
      two drugs are easily obtained by selecting the fluorine atom of the molecules.
      The images obtained show that flunitrazepam and flurazepam, two drugs of the
      benzodiazepine group are mainly located to the nuclei, whereas triflupromazine
      and trifluoperazine, two phenothiazines are exclusively located inside the
      cytoplasm.

PMID- 1348449
TI  - Differences in breast cancer risk factors to neu (c-erbB-2) protein
      overexpression of the breast tumor.
AB  - To investigate whether overexpression of the neu protein in breast tumors
      differentiates risk factor patterns for breast cancer, neu protein overexpression
      was determined in 296 breast carcinomas of patients participating in an ongoing
      population-based case-control study. Risk factor information on these patients
      and 737 controls was obtained during home interviews. Most breast cancer risk
      factors showed similar associations with neu-positive and neu-negative tumors,
      but remarkable differences were found for breast-feeding and age at first full
      term pregnancy. In contrast to the slightly protective effect of breast-feeding
      in the neu-negative group, the risk of neu-positive breast cancer was 4.2-fold
      increased in women who ever breast-fed. Increasing age at first full-term
      pregnancy was positively associated with both neu-positive and neu-negative
      breast cancer, but the association was about 2 times stronger for neu-positive
      tumors. We conclude that neu oncogene overexpression of the breast tumor seems to
      be associated with a distinct risk factor pattern.

PMID- 1348448
TI  - Effect of P-glycoprotein expression on the accumulation and cytotoxicity of
      topotecan (SK&F 104864), a new camptothecin analogue.
AB  - Topotecan (TPT, 9-dimethylaminomethyl-10-hydroxycamptothecin) is the first
      topoisomerase I-directed cytotoxic agent to enter clinical trials in the United
      States in two decades. The effect of P-glycoprotein (Pgp) overexpression on TPT
      cytotoxicity was examined in CHRC5 (colchicine-resistant) and AuxB1 (parental)
      Chinese hamster ovary cells. Examination of the IC50 values observed in colony
      forming assays revealed that the CHRC5 cells were 15-fold (SD, +/- 3; n = 3)
      resistant to TPT after a 1-h exposure and 3.2-fold (SD, +/- 1.4; n = 4) resistant
      in continuous exposure experiments. Band depletion immunoblotting revealed that 4
      fold higher concentrations of extracellular TPT were required to induce the
      formation of topo I-DNA complexes in CHRC5 cells as compared to AuxB1 cells. To
      assess the role of Pgp in this resistance, drug accumulation and cytotoxicity
      assays were repeated in the absence and presence of quinidine. Addition of
      quinidine enhanced TPT accumulation (measured by high-performance liquid
      chromatography) and diminished the IC50 for TPT to a greater extent in CHRC5
      cells than in AuxB1 cells. To examine whether similar effects could be detected
      in Pgp-expressing human cells, MCF-7/Adriar breast cancer cells and KG1a human
      acute myelogenous leukemia cells were examined. Quinidine or verapamil enhanced
      TPT accumulation in both of these cell lines but had no effect in parental MCF-7
      cells or a variety of human leukemia cell lines that do not overexpress Pgp.
      Cytotoxicity measurements performed by counting the number of surviving cells
      (MCF-7/Adriar) or employing a modified, highly stable tetrazolium dye reduction
      assay (leukemia cell lines) revealed that quinidine diminished the IC50 for TPT
      in the Pgp-overexpressing cell lines but not in the control lines. These results
      suggest that Pgp overexpression diminishes TPT accumulation and TPT cytotoxicity
      in hamster and human cells. It should be stressed, however, that these effects
      were substantially smaller than the effects of Pgp overexpression on the
      accumulation and cytotoxicity of the anthracycline daunorubicin and the
      epipodophyllotoxin etoposide in the same cell lines.

PMID- 1348450
TI  - Molecular analysis of the chromosome 11p region in renal cell carcinomas.
AB  - Comparative histological data suggest that papillary renal cell tumors in adults
      and Wilms' tumors in children develop from maturation-arrested cells of similar
      origin. Wilms' tumor is characterized by genetic changes at the chromosome 11p
      region. In the present study, we have analyzed 10 papillary and 10 non-papillary
      renal cell tumors and determined the allelic status of 6 loci on the short arm of
      chromosome 11. Only one papillary renal cell carcinoma among the 20 tumors showed
      a loss of constitutional heterozygosity for the chromosome 11p region. These data
      suggest that separate molecular events occur in the development of Wilms' tumor
      and papillary renal cell tumors, subsequent to the proliferation of maturation
      arrested cells of the kidney.

PMID- 1348451
TI  - The role of thyroid stimulating antibody (TSAb) in the thyroid function of
      patients with post-partum hypothyroidism.
AB  - OBJECTIVE: We investigated the association between thyroid function and the
      biological activities of thyroid stimulating antibodies (TSAb) and thyroid
      stimulation blocking antibodies (TSBAb) in patients with post-partum
      hypothyroidism. DESIGN: A prospective study. PATIENTS: We studied 25 patients
      with post-partum hypothyroidism who visited our thyroid clinic during the period
      from 1985 to 1990. MEASUREMENTS: We measured TSH binding inhibitory
      immunoglobulin (TBII) and TSAb activity at the initial presentation of each of
      the 25 patients. Women found to have elevated TSAb activity were followed up.
      Upon finding negative TSAb activity along with positive TBII activity in the
      serum at the initial presentation, we measured TSBAb activity. Women found to
      have elevated levels of TSBAb at the initial presentation were also followed up.
      RESULTS: Elevated TBII activity was found in six of the 25 patients, as was high
      TSAb activity (205-2651%, normal 55.0-145.0%) in five of these six and in one
      other patient at the initial presentation. Markedly elevated TSBAb activity (89%)
      was found in one TBII positive patient. We were able to follow up serially five
      TSAb positive patients and the TSBAb positive patient over periods ranging from
      11.5 to 26.5 months post-partum. The maximal value of TSAb activity was observed
      at the initial presentation in all TSAb positive patients, following which the
      activities gradually decreased. One of these patients developed Graves'
      hyperthyroidism associated with high TSAb activity (1223%) at 10.5 months post
      partum. One of the other patients was restored to euthyroid with elevated TSAb
      activity (279%), but thereafter developed hypothyroidism in conjunction with the
      disappearance of TSAb activity at 26.5 months post-partum. In the other two
      patients, normalization of thyroid function was observed with elevated TSAb
      activity. Thereafter, thyroid function remained within the normal range even with
      the disappearance of TSAb activity. In the other patient, normalization of
      thyroid function was observed at 11.5 months post-partum, 3 months after the
      disappearance of TSAb activity. In the TSBAb positive patient, TSBAb activity
      decreased to 21% by 17.5 months post-partum associated with normalization of
      thyroid function. CONCLUSION: The present study demonstrates the presence of
      elevated levels of TSAb activity in some patients with post-partum
      hypothyroidism. In these patients, Graves' hyperthyroidism may be induced by TSAb
      activity, and hypothyroidism may reoccur with the disappearance of the TSAb
      activity. Furthermore, post-partum hypothyroidism may be due to increased TSBAb
      activity in some patients.

PMID- 1348453
TI  - Recent advances in placental ion transport.

PMID- 1348452
TI  - Pharmacokinetics and dose proportionality of D2-agonist MK-458 (HPMC) in
      parkinsonism.
AB  - To investigate the pharmacokinetic profile, bioavailability, and dose
      proportionality of the D2-agonist MK-458 (hydroxypropylmethylcellulose tablet, a
      sustained release formulation), a 4-period crossover study was conducted in 10
      patients with mild to moderate Parkinson's disease (mean age = 63 y; 1 woman, 9
      men). Following a titration phase to induce tolerance, each patient was given
      single oral doses of 6, 12 and 18 mg and a single intravenous 40 micrograms dose
      (5 micrograms/h over 8h). The maximum concentrations of MK-458 observed in plasma
      after oral administration were 139, 240 and 344 ng/L for the 6, 12 and 18 mg
      doses, respectively, and occurred after 8.0, 9.0 and 5.5 h, respectively. Mean
      areas under the plasma concentration-time curves were 1728, 2849 and 5484 ng/L.h,
      respectively. The mean plasma half-life was 3.8 h and mean plasma clearance was
      3390 ml/min (203.4 L/h). The bioavailability (approximately 5%) was very similar
      for the 3 tablet formulations tested. The disposition of MK-458 was independent
      of the dose over the range of doses studied.

PMID- 1348454
TI  - Selective brain cooling in desert animals: the camel (Camelus dromedarius).
AB  - 1. Animals living in the Arabian desert are subjected to extremely high
      temperatures during the day in summer and very cold nights in winter. They have
      developed various adaptive mechanisms in order to cope with these severe heat
      conditions. 2. The camel (Camelus dromedarius), like many other land animals,
      resorts to selective brain cooling when it is subjected to heat stress. 3. This
      mechanism protects the heat-sensitive brain tissue from heat stress and at the
      same time increases the animals' tolerance to high temperatures. 4. The blood
      cooled in the nasal cavity by evaporative heat loss is diverted to the brain
      sinuses via the nasal and angular veins. 5. In the cavernous sinus, the arterial
      blood in the carotid rete is cooled by the cold venous blood before entering the
      brain. This will lead to significant cooling of the brain tissue. 6. Active
      myogenic tone was mainly observed in the facial, nasal and angular oculi veins of
      the camels head. This tone was found to be sensitive to small changes in
      temperature in the range 33-45 degrees C. 7. The facial veins constricted, while
      the nasal and angular oculi veins relaxed to increasing temperatures. This leads
      to a coursing of cold venous return to the brain's sinuses for selective brain
      cooling. 8. It is concluded that this myogenic vasoactive mechanism is a major
      factor in the control of blood flow in the facial area of the camel during heat
      stress.

PMID- 1348455
TI  - Na-transport during long-term incubation of the hen lower intestine: no
      aldosterone effect.
AB  - 1. In order to test the aldosterone effect in vitro, Na-transport of the
      coprodeal epithelium from hens on low-NaCl diet was measured in the Ussing
      chamber for up to 8 hr. Short-circuit current (SCC, near equal to the amiloride
      inhibitable Na-transport) was recorded. 2. Incubation media were either Krebs
      phosphate or bicarbonate buffer with and without addition of beta
      hydroxybutyrate, glutamine and mannose as "metabolic fuels". The media were
      replaced every hour. The Krebs-phosphate buffer was further tested with and
      without indomethacin and media replacement. Na-transport was best maintained in
      this buffer with replacement: SCC at 4 hr: 156 +/- 21 microA/cm2, 8 hr: 73 +/- 14
      microA/cm2. 3. The aldosterone experiments were carried out on tissues from hens
      resalinated for 24 hr. No effects were demonstrated at concentrations up to 10(
      5) M. The SCC showed an unexpected raise within 2-4 hr to a very high level (4
      hr: 221 +/- 61 microA/cm2) both in the control and in all aldosterone-treated
      tissues. This SCC decreased slowly to 210 +/- 29 microA/cm2 at 8 hr. It was
      abolished by amiloride. 4. No increase in SCC was observed in tissues from hens
      after 48 and 72 hr of resalination either after aldosterone or on chronic high
      NaCl diet.

PMID- 1348456
TI  - Thermogenic, thermolytic and body temperature effects of fenfluramine, a 5
      hydroxytryptamine agonist, in the domestic fowl (Gallus domesticus).
AB  - 1. Intramuscular injection of the 5-HT agonist DL-fenfluramine increased the
      metabolic rate of mature cockerels by about 25% over the following 22 hr. The
      acute effect, over the 3 hr following injection, attained 40% at 10 degrees C,
      35% at 20 degrees C and 25% at 32 degrees C. 2. Heat loss mechanisms (peripheral
      vasodilatation, postural change and panting) were also stimulated, to an extent
      which varied with ambient temperature. 3. Food intake, respiratory quotient and
      locomotor activity were significantly reduced by fenfluramine injection. 4. The
      opposing effects on heat production and heat loss had an influence on deep-body
      temperature which varied from a reduction of 0.5 degrees C at 10 degrees C
      ambient to an increase of about 0.5 degrees C at 32 degrees C. 5. The 5-HT
      blocker, methysergide, prevented the effects of fenfluramine on both heat
      production and heat loss for about 5 hr after injection. 6. The autonomic
      ganglion blocker, hexamethonium chloride, reduced the thermogenic but not the
      heat-loss effects of fenfluramine. 7. The results suggest that DL-fenfluramine
      has centrally-occurring but independent effects on heat production and a number
      of heat loss effectors, and that the heat production effect is mediated by the
      autonomic nervous system. The effect of fenfluramine on deep-body temperature
      appears to result from an altered equilibrium between heat production and heat
      loss.

PMID- 1348457
TI  - The kinetics of homosynaptic short-term depression in cell RPa3 of Helix pomatia
      depends upon the level of activity prior to depression.
AB  - 1. Following synaptic rest periods of 2 min, recovery from EPSP depression was
      dominated by a monoexponential phase completed within 2 min. After rest periods
      of 6 min, a two-phased recovery occurred: a transient phase followed by a slow
      phase lasting 10 min. 2. The shift of recovery kinetics was associated with a
      change of the time course of depression: following rest periods of 2, 6 and 12
      min, EPSP trains of 1/10 Hz gave three different depressions. 3. The change of
      recovery inverted a logarithmic proportionality between frequency of EPSPs and
      degree of depression to an inverse relation.

PMID- 1348458
TI  - Ureotelism as the prevailing mode of nitrogen excretion in larvae of the
      marsupial frog Gastrotheca riobambae (Fowler) (Anura, Hylidae).
AB  - 1. Embryos from the pouch of the marsupial hylid frog Gastrotheca riobambae
      excrete urea. 2. Free-living tadpoles of G. riobambae excrete mainly urea, in
      comparison with tadpoles of other hylid frogs. 3. The activity of arginase is
      high in embryos from the pouch, and in tadpoles of G. riobambae. 4. The
      ureotelism of G. riobambae larvae is an adaptation for prolonged incubation in
      the pouch of the mother, and for development in limited amounts of water.

PMID- 1348459
TI  - The response of statocyst receptors of the lobster, Homarus americanus, to
      movements of statolith hairs.
AB  - 1. While recording from the statocyst nerve of Homarus americanus, we deflected
      the statolith hairs from the "rest" position they assumed after the lith was
      removed. 2. Each of the smaller statocyst hairs apparently drove three sensory
      receptors; all receptors were sensitive to hair position, hair movement velocity,
      and hair movement direction. 3. Two of the receptors, types A and C, only
      responded when the hair was lifted up and away from rest; the third, type B, only
      responded vigorously when a hair was moved back toward rest from such a
      deflexion. 4. Type A and B receptors were phasic-tonic; type C receptors were
      phasic.

PMID- 1348460
TI  - Statolith hair movements and the regulation of tonic gravity reflexes in the
      lobster, Homarus americanus.
AB  - 1. The irregularity of the statolith of the lobster, Homarus americanus, probably
      causes a large and haphazard variation in the response of the individual
      statocyst receptors to body rotation. 2. Lobster gravity reflexes are regulated
      by the summed responses of the statocyst receptors; this probably compensates for
      the haphazard variation in the sensory input.

PMID- 1348461
TI  - Distribution and vasomotor effects of neuropeptides in angular oculi and facial
      veins of reindeer.
AB  - 1. The vasomotor responses to neuropeptides of the angular oculi and facial veins
      of reindeer were examined in vitro and correlated with the neuropeptide
      distribution in the perivascular nerves, as demonstrated by immunohistochemistry.
      2. Nerves displaying calcitonin gene related peptide (CGRP)- or neuropeptide Y
      (NPY)-like immunoreactivity (-LI) were observed in the media of both veins, while
      very few fibers were immunoreactive to vasoactive intestinal polypeptide (VIP) or
      substance P (SP) in either vein. 3. The staining pattern for NPY-LI was largely
      identical to that of dopamine-beta-hydroxylase, a marker for noradrenaline (NA)
      producing fibers, indicating coexistence of NPY and NA. 4. Administration of NPY
      in vitro elicited contractions in both veins in the presence of propranolol,
      though more conspicuously in the angular oculi vein. 5. The peptide was without
      any modulating effect on NA-stimulated contractions in the angular oculi vein,
      whereas a small enhancement of the NA-induced tone was seen in the facial vein.
      6. CGRP caused partial relaxation of both veins, whereas atrial natriuretic
      polypeptide caused relaxation only in the facial vein. VIP and SP had no effect
      on either vein. 7. The results suggest that in reindeer the sympathetic nerve
      fibres to both facial and angular oculi veins contain the vasoconstrictor
      neuropeptide NPY besides NA, even though these fibres exert a vasodilator action
      on the myogenically active facial vein. 8. The vasodilator neuropeptide CGRP,
      which is present in other more sparse perivascular nerve fibres mainly in angular
      oculi vein, is perhaps of afferent nature in which case CGRP might subserve axon
      reflex functions. 9. If, however, also the CGRP fibres are truly efferent in
      nature, chances for a central reciprocal control of flow through angular oculi
      vein might be at hand.

PMID- 1348462
TI  - Localization, cellular morphology and respiratory capacity of "brown" adipose
      tissue in newborn reindeer.
AB  - 1. The localization and cellular morphology of adipose tissue was studied by
      light, fluorescence and electron microscopy in reindeer between 2 weeks pre
      partum and 4.5 months post partum during calving, and the subsequent growth
      period. The respiratory capacity of the adipose tissue was examined in terms of
      morphometric mitochondrial volume and cytochrome-c oxidase or succinate
      dehydrogenase activity. 2. Adipose tissue was located at specific anatomical
      sites in the newborn reindeer (from 0 to 2 days of age). The perirenal-abdominal
      depot was the largest location (32%) followed by the inter(pre)scapular (18%) and
      sternal (12%) depots. Internal depot dominated over external or peripheral depots
      (66-34%). The locations of adipose tissue were largely similar in foetal, newborn
      and young reindeer. 3. The adipose tissue of the newborn reindeer had all the
      typical cell morphological characteristics of brown adipose tissue: abundant
      mitochondria, multilocular fat, high vascularization and a dense spot-like
      sympathetic innervation between the adipocytes. In the young reindeer, however,
      it resembled white adipose tissue, being almost totally unilocular with few
      mitochondria. 4. There was a significant correlation between morphometric
      mitochondrial volume and cytochrome-c oxidase activity (r = 0.848) in the adipose
      tissue. Mitochondrial volume, cytochrome-c oxidase and succinate dehydrogenase
      activity were highest after birth and decreased to almost an undetectable level
      during the first month. A parallel decrease occurred in the amount of brown
      adipose tissue from birth (1-2%) to the age of about one month (0.3%). 5. It is
      concluded that the distinct cell morphological features and high respiratory
      capacity of the adipose tissue indicate the presence of brown adipose tissue at
      specific anatomical locations in newborn reindeer. A marked progression towards
      the characteristics of white adipose tissue then takes place at the same
      locations during the first month. The results suggest the fundamental
      significance of brown adipose tissue for non-shivering thermogenesis in newborn
      reindeer.

PMID- 1348463
TI  - Dependence of the sympatho-adrenal activity on the nutritional status in
      corticosterone treated rats.
AB  - 1. An integrated sympatho-adrenal (SA) activity, expressed in terms of urinary
      catecholamines (CA) excretion, and direct sympathetic activity in the
      interscapular brown adipose tissue (IBAT), expressed in terms of noradrenaline
      (NA) turnover, were studied in corticosterone treated stock fed and sucrose
      overfed rats. 2. Corticosterone in stock fed rats significantly decreased both
      the rate of IBAT NA turnover and its mass as well as urinary NA excretion but did
      not change either IBAT NA content, urinary adrenaline excretion or adrenal CA
      content. 3. Sucrose overfeeding significantly increased SA activity, i.e. the
      rate of NA turnover in the IBAT and urinary excretion of CA. However,
      corticosterone did not inhibit the sucrose-induced sympathetic nervous system
      activation but potentiated the activity of adrenal medulla. 4. The results
      suggest that the effect of corticosterone treatment on the SA activity in rats is
      dependent, in addition to other factors, on the nutritional status of the
      animals.

PMID- 1348464
TI  - Miracidium of Schistosoma mansoni: a macromolecular glycoconjugate as signal for
      the behaviour after contact with the snail host.
AB  - 1. The behaviour of the miracidium of Schistosoma mansoni after contact with agar
      blocks containing Biomphalaria glabrata snail conditioned water (SCW) or its
      components, was studied. 2. "Repeated investigation" was the most specific
      response at contact with the snail host. 3. Fractionation and specific chemical
      treatment of SCW revealed that this response was stimulated by a lysozyme
      sensitive glycoconjugate with a mol. wt greater than 300,000. 4. Low molecular
      weight components of SCW had no stimulatory effect on the miracidia, although
      MgCl2 offered as pure chemical did so.

PMID- 1348465
TI  - Seasonal changes in the tolerance of osmotic stress in natterjack toads (Bufo
      calamita).
AB  - 1. Bufo calamita were exposed to tap water to solutions of urea (up to 1000 mM)
      and NaCl (up to 250 mM). 2. The effects of season and nutrition on the adaptation
      to osmotic stress were studied by monitoring body mass, moulting rate,
      hematocrit, plasma osmolality and the plasma concentrations of urea, chloride and
      glucose. 3. There were marked seasonal changes in the time of survival in tap
      water as well as in the ability to acclimate to high concentrations of urea and
      NaCl. 4. The maximal concentration of urea in the plasma of starving toads was
      greater in winter (650 mM) than in summer (410 mM), but fed toads also reached
      winter levels (653 mM) during summer. 5. Salt acclimation was accompanied by urea
      accumulation in plasma up to 175 mM. 6. Salinities exceeding 454 mOsmol/l of NaCl
      were lethal.

PMID- 1348466
TI  - A time course study of the isometric contractile properties of rat extensor
      digitorum longus muscle injected with bupivacaine.
AB  - 1. The effect of intramuscular injections of the myotoxin bupivacaine on the
      isometric contractile properties of rat extensor digitorum longus (EDL) muscle
      was studied. 2. Immediately after injection the EDL muscle did not contract when
      stimulated. The absolute (mN) and normalized (N/g) peak twitch (Pt) and tetanic
      (PO) tensions gradually returned to normal by 21 days after injection. 3.
      Thereafter, the injected muscles grew at an accelerated rate and by 80 days were
      70% heavier than controls. 4. The hypertrophy was not paralleled by a
      proportional increase in absolute Pt and Po and consequently the normalized Pt
      and Po were 30% less than controls.

PMID- 1348467
TI  - The use of purified condensed tannin as a reference in determining its influence
      on rumen fermentation.
AB  - 1. Tannins were purified from the leaves of trees forming part of giraffe's diet
      in the Kruger National Park. 2. In general, hydrolysable tannin formed less than
      10% of the total purified crystal complexes, condensed tannin and possibly some
      non tannin phenols forming the balance. 3. Each tree species condensed tannin
      gave a different calibration curve and these were used in the assay. 4. Volatile
      fatty acid production during in vitro fermentation was greatly reduced when the
      substrate contained more than 6% condensed tannin.

PMID- 1348468
TI  - Differences in fatty acid composition of various tissues of the marmoset monkey
      (Callithrix jacchus) after different lipid supplemented diets.
AB  - 1. The fatty acid composition of different muscles, organs and blood components
      of the marmoset monkey were examined after long-term feeding of several well
      defined lipid supplemented diets. 2. Similarities between the fatty acid
      composition of cardiac and skeletal muscles which persisted after all diets
      suggest that biopsy of skeletal muscle may have an important diagnostic value in
      this and other primate species. 3. The relationship between the dietary intake of
      individual fatty acids and their proportions in different tissues is both complex
      and variable. 4. However, the lipid metabolism of Callithrix jacchus recommends
      this small non-human primate as a most suitable species for the study of lipid
      nutrition.

PMID- 1348470
TI  - Financing the costs of diabetes mellitus in the 1990's. Proceedings of a
      symposium of the Second National Conference on Financing the Care of Diabetes
      Mellitus. Washington, D.C., 3-5 December 1989.

PMID- 1348469
TI  - Effect of genetic dilution on development of diabetes, impaired glucose tolerance
      and in vitro glucose oxidation in LA/N-cp x SHR/N-cp F1 hybrid rats.
AB  - 1. To determine the effects of gene dilution on development of IGT, NIDDM and in
      vitro glucose oxidation, heterozygous lean LA/N-cp female and SHR/N-cp male rats
      were mated, and F1 offspring studied at periodic intervals to determine the
      prevalence of obese and diabetic traits. 2. Obesity occurred in 25% of offspring
      by 5 weeks of age, consistent with inheritance of the autosomal recessive cp
      trait. 3. IGT occurred in all obese male F1, 67% of obese female F1, and 18% of
      the lean male F1 rats by 5 months of age, and diabetes occurred in 80% of male
      obese and 17% of female obese rats from 6 months of age. Glycosuria occurred with
      glucose intolerance, and was more severe in rats with NIDDM than IGT. 4. Rates of
      in vitro glucose oxidation were greater in diaphragm and adipose tissue, and were
      greater in the presence of insulin (100 mu Units/ml) in obese female but not
      obese male F1 rats. 5. These results indicate that the development of glucose
      intolerance is more prominent in male than in female F1 rats, that the
      progression of IGT to NIDDM occurs later in life in the F1 hybrid than in the
      SHR/N-cp strain from which the diabetic trait was transmitted, and that genetic
      dilution of the diabetic trait via hybrid breeding results in a delay in the
      expression of NIDDM which is chronologically more similar to that which occurs in
      man.

PMID- 1348471
TI  - Improving the financing of diabetes care in the 1990s. Recommendations of the
      1989 conference.

PMID- 1348472
TI  - Therapeutic biliary endoscopy.

PMID- 1348473
TI  - Serum beta-carotene before and after beta-carotene supplementation.
AB  - A two-month double-blind, placebo-controlled supplementation study of oral beta
      carotene (20 mg daily) was conducted. Two hundred and twenty two 30-69 year old
      men were randomized into either a beta-carotene or placebo group, and serum
      samples were obtained at baseline, follow-up (2 months), and up to 12 weeks post
      supplementation. Serum beta-carotene increased on average 10-fold in the beta
      carotene group, from 0.53 +/- 0.32 mumol/l (mean +/- SD) at baseline to 4.99 +/-
      2.47 mumol/l at follow-up (P less than 0.0001), and beta-carotene levels remained
      elevated up to 12 weeks post-supplementation (0.61 +/- 0.15 mumol/l). No changes
      in serum retinol, alpha-tocopherol, or total cholesterol were observed. At
      baseline, serum beta-carotene levels were positively correlated with dietary beta
      carotene (r = 0.29) and inversely correlated with body mass index and serum gamma
      glutamyltransferase (r = -0.33 and r = -0.40, respectively). The inverse
      association with body mass index and serum gamma-glutamyltransferase persisted
      during active supplementation, whereas the positive association with dietary beta
      carotene disappeared. In multivariate analysis, serum cholesterol was also
      positively associated with serum beta-carotene levels both before and after
      supplementation. Baseline serum beta-carotene was the factor most strongly
      associated (positively) with serum beta-carotene after supplementation. Our study
      highlights the importance of several factors which affect serum beta-carotene.

PMID- 1348476
TI  - Haemodynamic effects of H2-receptor antagonists.

PMID- 1348474
TI  - Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) in
      human penile corpus cavernosum tissue and circumflex veins: localization and in
      vitro effects.
AB  - Localization and functional effects of vasoactive intestinal polypeptide (VIP)
      and peptide histidine methionine (PHM), two peptides derived from a common
      precursor molecule, were investigated in isolated preparations from human penile
      corpus cavernosum (CC) and circumflex vein (CV). VIP- and PHM-immunoreactivity
      (IR) was demonstrated in both CC and CV. The concentrations of VIP-IR and PHM-IR
      in CC tissue were 54.4 +/- 15.3, and 42.0 +/- 7.5 pmol g-1 wet weight
      respectively with a VIP/PHM ratio of 1.5 +/- 0.4 (mean +/- SEM). The
      corresponding values for CV tissues were 28.0 +/- 7.7 and 9.6 +/- 2.6 pmol g-1
      wet weight with a VIP/PHM ratio of 3.1 +/- 0.4. CC and CV displayed VIP- and PHM
      IR confined to nerve fibres in close relation to bundles of smooth muscle cells
      and blood vessels in both tissues. In vitro, VIP and PHM had no effects in
      unstimulated tissue preparations. Both peptides concentration-dependently (10(-9)
      10(-6) M) relaxed CC and CV preparations precontracted with 3 x 10(-6) M
      noradrenaline. In CC the maximum relaxant effect of VIP and PHM was 22 +/- 11%
      and 9 +/- 9% and in CV the corresponding values were 82 +/- 8% and 93 +/- 3%
      respectively. The present study supports the hypothesis of VIP and PHM as
      neurotransmitters and/or neuromodulators in the nervous control of penile
      erection.

PMID- 1348475
TI  - Somatostatin does not block the effect of vasoactive intestinal peptide on bile
      secretion in man.
AB  - The effects of intravenously administered somatostatin and vasoactive intestinal
      peptide (VIP) on bile secretion were studied in 10 patients with complete biliary
      fistulas. The two peptides were administered both separately and simultaneously.
      During the infusion of vasoactive intestinal peptide, bile secretion increased by
      85%, whereas during somatostatin infusion it decreased by 40%. When the peptides
      were administered together, the VIP-induced choleretic effect was not reduced by
      somatostatin. Vasoactive intestinal peptide infusion increased bicarbonate
      concentration and output, whereas somatostatin had the opposite effect. The
      output of chloride also increased following vasoactive intestinal peptide
      infusion but decreased following somatostatin infusion. The concentration of
      chloride was unaffected by somatostatin whereas it was decreased by vasoactive
      intestinal peptide. The output of bile acids was unaffected by vasoactive
      intestinal peptide and decreased by somatostatin infusion, whereas total lipid
      concentration increased during somatostatin infusion and decreased when
      vasoactive intestinal peptide was added. It is concluded that, in man,
      somatostatin acts on the bile acid-dependent canalicular bile secretion and also,
      to some extent, on the ductular secretion, whereas vasoactive intestinal peptide
      acts strictly at the ductular level. The effects of the two peptides on bile
      secretion are independent of each other.

PMID- 1348477
TI  - The effects of light on cyclic nucleotide metabolism of isolated cone
      photoreceptors.
AB  - A procedure has been developed for the isolation of cone photoreceptors from the
      retina of the lizard Anolis carolinensis in order to study the effects of dark-
      and light-adaptation on the cyclic nucleotide metabolism of these visual cells.
      Incubation of the retina in N2 medium with hyaluronidase and DNAase allows us to
      obtain intact photoreceptors with good purity (85-90%), yields (greater than 2 x
      10(5) cells per retina), and more than 95% of them excluding Trypan blue. cAMP
      levels are 20-fold higher than cGMP levels in cells from dark-adapted animals and
      are decreased by 35% upon exposure to light, whereas cGMP levels show no apparent
      change. However, both cAMP- and cGMP-phosphodiesterases, as well as adenylate and
      guanylate cyclase, are activated several-fold by light, but the enzymes involved
      in cGMP metabolism have higher Vmaxs than the cAMP related enzymes. The apparent
      constant levels of cGMP found in cone photoreceptors may result from our
      inability to detect the very fast changes that occur in these cells when they are
      exposed to light.

PMID- 1348478
TI  - Origin of mutation in sporadic cases of haemophilia-B.
AB  - Of the 45 haemophilia-B patients registered at the haemophilia centre in Malmo,
      Sweden, 24 are the sole members of their families to be affected, and in 13 of
      these 24 cases, ascendant relatives are available for study. Detection of the
      gene defect showed the mutation to be de novo in the proband in 3 of these 13
      cases, and inherited from a carrier mother in the remaining 10 cases. All 10
      carrier mothers were shown to have de novo mutations, as the patients'
      grandfathers were phenotypically and/or haematologically normal, and the
      grandmothers were non-carriers. Seven restriction fragment length polymorphisms
      (RFLPs) of the factor IX gene were used to determine whether the de novo
      mutations of the 10 carrier mothers were of paternal or maternal origin. In 6/10
      cases, the RFLP patterns were informative, and indicated the mutation to be of
      paternal origin.

PMID- 1348479
TI  - Epidemiology of thrombocytopenia in HIV infection.
AB  - Thrombocytopenia is a known complication of human immunodeficiency virus Type-1
      (HIV-1) infection, and more data need to be collected on its frequency, severity,
      and clinical sequelae. We determined the frequency of thrombocytopenia and its
      relationship to other HIV infection characteristics from a review of records of
      1004 HIV-infected patients attending two outpatient clinics in Washington, D.C.
      The self-reported sources of HIV-1 exposure were male homosexual activity (68%),
      bisexual activity (10%), heterosexual activity (6%), and intravenous drug use
      (15%). Fifty-nine percent of the individuals were white, 37% were black and 94%
      were male. Fifteen percent had AIDS. Thrombocytopenia occurred more frequently in
      subjects with AIDS (21.2%) than in HIV-infected individuals who did not fit
      clinical criteria for AIDS (9.2%) (p less than 0.001). Patients with few CD4
      positive cells and an advanced stage of disease were more likely to have low
      platelet counts: 30% with an absolute CD4 cell count lower than 200/mm3 vs 8%
      with CD4 counts between 200 and 500 (p less than 0.00001), and 18.5% with Stage
      IV disease compared to 7.6% in Stage II (p less than 0.001) had platelet counts
      less than 150,000/mm3. Thrombocytopenia was more frequent in white males and
      older subjects. Although subjects infected by heterosexual exposure had a lower
      frequency of thrombocytopenia, intravenous drug users and homosexual men
      exhibited similar frequencies of thrombocytopenia. Of all subjects with platelet
      counts less than 50,000/mm3, 40% reported bleeding and 1 died of an intracranial
      hemorrhage. Thrombocytopenia occurs frequently in HIV-infected people, primarily
      in those with AIDS, low CD4 cell numbers, and advanced stages of diseases.

PMID- 1348480
TI  - Mediator concentrations in bronchoalveolar lavage fluid of patients with mild
      asymptomatic bronchial asthma.
AB  - Bronchoalveolar lavage (BAL) was performed on 11 atopic patients with mild
      asymptomatic bronchial asthma and 11 healthy nonasthmatic volunteers. All
      asthmatic subjects had evidence of bronchial hyperresponsiveness to inhaled
      carbachol. The concentrations of leukotriene (LT) C4, LTD4, LTE4, LTB4,
      prostaglandin D2 (PGD2), platelet-activating factor (PAF) and histamine in BAL
      fluid measured. The leukotrienes were measured by radioimmunoassay following
      reverse phase high performance liquid chromatography. PGD2 concentrations were
      determined by radio immunoassay after Amprep C2 extraction. PAF was quantitated
      by means of in vitro aggregation of rabbit platelets and histamine content was
      measured using a single isotope radio-enzymatic assay. There was an increase in
      the levels of PGD2 and a decrease in the concentration of LTB4 in asthmatic
      lavage samples. There were no significant differences in the lavage
      concentrations of LTC4/D4/E4 and histamine between the two groups of individuals.
      PAF was undetectable.

PMID- 1348481
TI  - Effects of celiprolol, a cardioselective beta-blocker, on respiratory function in
      asthmatic patients.
AB  - The aim of this study was to compare the pulmonary effects of a single dose of
      celiprolol 400 mg, versus bisoprolol 20 mg and the combination of celiprolol 400
      mg plus propranolol 40 mg versus placebo plus propranolol 40 mg. We conducted a
      double-blind randomized cross-over study in 10 stable asthmatic patients (mean
      age +/- SD 31 +/- 7 yrs) with forced expiratory volume in one second (FEV1): 2.5
      +/- 0.7 l. A three-day washout period preceded each treatment period.
      Measurements of respiratory function were done before treatment and after 90, 120
      and 180 min. There was a significant increase of FEV1 (+12%) and forced vital
      capacity (FVC) (+8%) after celiprolol (p less than 0.05) and a decrease of FEV1 (
      9%) after propranolol. Concerning the combination, celiprolol inhibits the
      bronchoconstrictor effects of propranolol. We conclude that celiprolol has
      bronchosparing properties in asthmatic patients, and even improves some of the
      ventilatory parameters.

PMID- 1348482
TI  - Nonadrenergic, noncholinergic airway inhibitory nerves.
AB  - Nonadrenergic, noncholinergic (NANC) nerves, which cause relaxation of airway
      smooth muscle, have been described in several species including man. Stimulation
      of efferent vagus nerves during cholinergic and adrenergic blockade induces a
      pronounced bronchodilation in the cat. In more recent studies in man, capsaicin
      inhalation or mechanical irritation of the larynx, under conditions of
      cholinergic and adrenergic blockade, have been shown to cause a transient
      bronchodilator response. There is some evidence that neuropeptides such as
      vasointestinal peptide (VIP) or peptide histidine methionine (PHM) may be the
      neurotransmitter of NANC nerves, but this is not conclusive. Nitric oxide may be
      another neurotransmitter. In mild asthma, the NANC bronchodilator response is
      similar to that observed in normal subjects; on the other hand, a reduction in
      VIP immunoreactivity has been reported in more severe patients. The contribution
      of NANC dilator nerves in pathophysiological situations is not known, but their
      effect may be modulated during allergic responses. Use of antagonists or
      inhibitors of putative neurotransmitters, and molecular biological techniques
      will be useful in defining both the physiological and pathophysiological roles of
      NANC inhibitory nerves in the airways.

PMID- 1348483
TI  - Pleuropulmonary changes during treatment of Parkinson's disease with a long
      acting ergot derivative, cabergoline.
AB  - A patient with Parkinson's disease, initially treated with bromocriptine and
      subsequently with cabergoline, developed progressive pleuropulmonary
      abnormalities during the latter therapy. These lesions even worsened for some
      weeks after interruption of cabergoline, which may possibly be related to the
      prolonged action of this drug. Thus cabergoline may cause similar pleuropulmonary
      abnormalities to bromocriptine.

PMID- 1348484
TI  - The combination of dissimilar alleles of the A alpha and A beta gene complexes,
      whose proteins contain homeo domain motifs, determines sexual development in the
      mushroom Coprinus cinereus.
AB  - The A mating-type factor is one of two gene complexes that allows mating cells of
      the mushroom Coprinus cinereus to recognize self from nonself and to regulate a
      pathway of sexual development that leads to meiosis and sporulation. We have
      identified seven A genes separated into two subcomplexes corresponding to the
      classical A alpha and A beta loci. Four genes, one alpha and three beta, all
      coding for proteins with a homeo domain-related motif, determine A-factor
      specificity; their allelic forms are so different in sequence that they do not
      cross-hybridize. It requires only one of these four genes to be heteroallelic in
      a cell to trigger A-regulated sexual development, and it is the different
      combinations of their alleles that generate the multiple A factors found in
      nature. The other three genes cause no change in cell morphology and may regulate
      the activity of the four specificity genes.

PMID- 1348485
TI  - Specific activation of mammalian Hox promoters in mosaic transgenic zebrafish.
AB  - Homeo box-containing genes (Hox) are expressed in restricted regions of
      vertebrate embryos and may specify positional information. The organization and
      expression patterns of these genes are highly conserved among different species,
      suggesting that their regulation may also have been conserved. We developed a
      transient expression system, using mosaically transgenic zebrafish, which allows
      rapid analysis of transgene expression, and examined the activities of two
      mammalian Hox genes, mouse Hox-1.1 and human HOX-3.3. We found that these Hox
      promoters are activated in specific regions and tissues of developing zebrafish
      embryos and that this specificity depends upon the same regulatory elements
      within the promoters that specify the spatial expression of these genes in mice.
      Our results suggest that the promoter activities have been remarkably conserved
      from fish to mammals. To study the regulation of Hox expression in the developing
      nervous system, we analyzed the promoter activities in spt-1 mutants that have a
      mesodermal deficiency. Our results suggest that interactions, probably with the
      paraxial mesoderm, differentially regulate the activities of Hox promoters in the
      developing nervous system.

PMID- 1348486
TI  - [Safety in the therapy of urinary incontinence. II. Specialty workshop, 22nd
      Congress of the International Society of Urology. Seville, 4 November 1991].

PMID- 1348487
TI  - [New and better drugs patterned after nature. Report from the Press Workshop of
      Merckle, Inc. Blaubeuren, 1-3 November 1991, Frankfurt, Neu-Isenburg: "gene
      technique and medicine. Risk-possibilities-hopes"].

PMID- 1348488
TI  - [Properties and activation by lysophospholipids and fatty acid of membrane-bound
      guanylate cyclase in lymphocytes and erythrocytes from mouse spleen].
AB  - To clarify the properties of membrane-bound guanylate cyclase of lymphocytes and
      a functional role of lysophospholipids, the enzymic properties of membrane-bound
      guanylate cyclase and the effects of lysophospholipids and a free fatty acid with
      Ca2+ on the cyclase in lymphocyte and erythrocyte membrane fractions prepared
      from mouse splenic whole cells were examined. The membrane-bound guanylate
      cyclase activities of lymphocyte and erythrocyte membrane fractions from splenic
      whole cells were activated markedly by several lysophospholipids and linoleate.
      Lysophospholipids were divided into three groups according to their effects on
      the cyclase. 1) The first group of lysophospholipids exhibited the concentration
      activity curve which was similar to that of linoleate. 2) The second group showed
      the curves which were markedly different in the presence and absence of Ca2+. 3)
      The third group had no effects on the enzyme activity. The membrane-bound
      guanylate cyclase activity in the erythrocyte membrane fractions was about 2
      times stronger than that in the lymphocyte fractions. On the other hand, the
      membrane-bound guanylate cyclase activity in the erythrocyte fractions from
      peripheral blood was not enhanced by these substances. The marked activation of
      the guanylate cyclase by lysophospholipids and linoleate is considered to have
      important significance in the regulation of cGMP-mediated signal transduction.

PMID- 1348489
TI  - The human cationic amino acid transporter (ATRC1): physical and genetic mapping
      to 13q12-q14.
AB  - The product of the mouse Rec-1 locus is an integral membrane protein that
      determines susceptibility to infection by murine ecotropic retroviruses. Recently
      it has been determined that its role in normal cell metabolism is transport of
      the cationic amino acids, arginine, lysine, and ornithine across the plasma
      membrane. Southern blot analysis of genomic DNA from a panel of 48 mouse-human
      somatic cell hybrids assigned the human version of this gene, ATRC1, to
      chromosome 13. Chromosomal in situ hybridization localized the gene to 13q12-q14.
      A restriction fragment length polymorphism (RFLP) was detected with TaqI. There
      were two alleles with frequencies of 0.29 and 0.71. Pairwise linkage analysis
      established linkage between ATRC1 and ATP1AL1, D13S1, D13S6, D13S10, D13S11,
      D13S21, D13S22, D13S33, D13S36, and D13S37. Multilocus linkage analysis of five
      of the loci indicated that the most likely order of loci in this region was
      D13S11-ATP1AL1-ATRC1-D13S6-D13S33.

PMID- 1348490
TI  - Linkage mapping of human chromosome 10 microsatellite polymorphisms.
AB  - Ten microsatellite DNA polymorphisms located on human chromosome 10 were
      regionally mapped using subchromosomal somatic cell hybrids and linkage analysis.
      The resulting order of the markers from pter-qter was [D10S89, D10S111], D10S107,
      D10S109, [D10S91, D10S110, D10S108, D10S88, D10S168], and D10S169. Order of the
      markers within brackets was uncertain, although the order given was most likely.
      The microsatellites were distributed along the chromosome from the proximal p arm
      to near qter, with an unlinked gap between D10S168 and D10S169.

PMID- 1348491
TI  - Report of the second chromosome 11 workshop.

PMID- 1348492
TI  - The multi-locus H-2Dw16 region has an organization distinct from the Dd region.
AB  - Genomic DNA blot analyses using probes derived from the BALB/c 3' flanking region
      of the Ld gene (Ld 3' fl-C) and from near the BALB/c D3d gene (50.2A) indicate
      that the B10.GAA37 mouse strain has a multi-locus D (Dw16) region distinct from
      the five-gene organization observed in the Dd and Dq regions. To isolate the Dw16
      region class I genes, a genomic B10. GAA37-lambda EMBL3 library was generated and
      screened with probes that preferentially hybridize to K and D region class I
      genes. Hybridization analyses of the isolated lambda clones with Ld derived
      oligonucleotide probes suggested that one of the lambda clones contained the Lw16
      gene, whereas several other lambda clones contained the Dw16 gene. The sequence
      of the Dw16 gene is most similar to that of the Dp gene, particularly in the 3'
      half. Furthermore, the Lw16 gene is quite similar in the 5' half and virtually
      identical in the 3' half to the Ld gene, indicating that Lw16, but not Dw16, is a
      member of the Ld gene family. Collectively, these data suggest that, through a D
      region recombination event, the novel Dw16 region may have been assembled from
      primordial counterparts of the Dp and Ld genes.

PMID- 1348493
TI  - Tumor induction by the LTR, v-src, LTR DNA in four B (MHC) congenic lines of
      chickens.
AB  - We report that the cloned DNA harboring the long terminal repeat (LTR), v-src,
      LTR proviral structure is tumorigenic in chickens of the Prague congenic lines.
      The growth rate of these tumors is by far the highest in the recombinant CC.R1
      line, the B haplotype of which is composed of the B-F/L4 and B-G12 subregions
      originating from different naturally occurring haplotypes. Some of the tumors
      induced by the LTR, v-src, LTR DNA are repeatedly transplantable in syngeneic
      chickens, maintain unaltered provirus, and express v-src mRNA. Differences in the
      response to challenge with Rous sarcoma virus (RSV) and LTR, v-src, LTR DNA on a
      given experimental model are compared and possible involvement of an interaction
      between B-F/L and B-G region genes is considered. Regression of the LTR, v-src,
      LTR DNA-induced tumors did not prevent the formation and growth of tumors induced
      subsequently by RSV.

PMID- 1348494
TI  - Mapping of the genes encoding tum- transplantation antigens P91A, P35B, and P198.
AB  - Tum- comprises a class of genes, mutation of which in P815 tumor cells has led to
      the acquisition of new cytotoxic T cell-recognized epitopes. The cells carrying
      the mutant alleles have impaired tumorigenicity compared with their progenitors
      due to in vivo induction of a cytotoxic T-cell response specific for tum-
      antigens. Two tum- genes, P91A and P35B, were found to be single copy loci
      mapping to chromosomes 11 and 15 respectively. A third, P198, was found to map to
      chromosome 7 and to be a member of a small gene family with other members on
      chromosomes 13, 14, and 15. Multiple P198-related sequences were found in other
      mammalian species suggesting the P198 related gene family is a general feature of
      mammalian genomes.

PMID- 1348495
TI  - Alleles of the rat T-cell receptor beta chain gene complex.
AB  - Inbred rat strains provide a rich source of genetic diversity in immunologically
      relevant genes. We have characterized the alleles of one of these genes, encoding
      the rat T-cell receptor C beta 1 chain, by Southern blots and nucleic acid
      sequencing. The Cb1 gene segments from DA and LEW rats display complex allotypic
      variation: both coding and noncoding regions contain multiple nucleotide
      substitutions. In addition, there is a polymorphic insertion of a rat repetitive
      LINE element 3' to the coding region. The Cb1 alleles are one part of larger Tcrb
      haplotypes, containing V beta, D beta, and J beta elements; complete Cb1 genomic
      nucleotide sequences, and a partial list of the strain distribution of the two
      alleles, are described in this report.

PMID- 1348496
TI  - An unusual allelic form of the immunoglobulin lambda constant region genes in the
      Japanese.

PMID- 1348498
TI  - Ca2+ mobilization in nontransformed ciliary nonpigmented epithelial cells.
AB  - To investigate the calcium second messenger system in nonpigmented epithelial
      (NPE) cells, we studied drug-dependent cytosolic free Ca2+ concentration
      ([Ca2+]i) transients in cultured nontransformed human and rabbit NPE cells with a
      fluorescent Ca2+ indicator, fura-2, and a digital video-imaging system. The main
      findings of this study were: (1) The basal [Ca2+]i was 141.9 +/- 1.2 nM (mean +/-
      standard error of the mean, n = 401) in humans and 157.0 +/- 1.4 nM (mean +/-
      SEM, n = 346) in rabbits. (2) Isoproterenol (10(-4) M) had little effect on
      [Ca2+]i mobilization in both species. Norepinephrine (10(-4) M) and epinephrine
      (10(-4) M) increased [Ca2+]i in 56% and 78% of rabbit NPE cells by 1.8- and 2.1
      fold of basal [Ca2+]i, respectively, but induced little [Ca2+]i change in human
      NPE cells. Carbachol (10(-3) M) elicited significant [Ca2+]i increase (more than
      3-4-fold of basal level) in about 60-70% of NPE cells in both species.
      Heterogeneity was seen in the cellular response to these agonists. (3)
      Norepinephrine-induced response was blocked by phentolamine (10(-5) M), and the
      effect of carbachol was blocked by atropine (10(-4) M). (4) Time course of
      norepinephrine-induced [Ca2+]i change was primarily monophasic. In contrast,
      [Ca2+]i transients induced by carbachol were mostly biphasic. (5) The duration of
      carbachol- or norepinephrine-induced responses were shortened by the chelation of
      extracellular Ca2+ without affecting other parameters of the reaction. This study
      confirms the presence of the calcium signaling system in cultured nontransformed
      human and rabbit NPE cells.

PMID- 1348497
TI  - Sequence of the tumor necrosis factor/cachectin (TNF) gene from Peromyscus
      leucopus (family Cricetidae).

PMID- 1348499
TI  - Neurotransmitters and neuropeptides stimulate inositol phosphates and
      intracellular calcium in cultured human nonpigmented ciliary epithelium.
AB  - The effects of several neurotransmitters and neuropeptides on the inositol
      phosphate/diacylglycerol pathway were examined in human nonpigmented ciliary
      epithelial cells. Maximal stimulation of inositol phosphate formation by
      vasopressin (approximately 3-fold), carbachol (approximately 2-fold) and
      histamine (approximately 5-fold) was observed only after cells had been confluent
      for at least six days. In contrast, a response to bombesin (approximately 3-fold)
      declined with extended time in confluent culture. Inositol monophosphate,
      inositol bisphosphate, and inositol trisphosphate all were stimulated by these
      agonists. Dose-response studies showed a close correlation between the EC50s of
      the different agonists when elevation of inositol phosphates was compared to
      stimulation of intracellular Ca2+, with the exception of bombesin. Preliminary
      pharmacologic characterization of the receptors for vasopressin, carbachol, and
      bombesin provided rank order of potencies for selective agonists and antagonists.
      The data suggest that the muscarinic receptor on human NPE cells is the M3
      subtype, whereas the vasopressin receptor, as defined by its linkage to the
      inositol phosphate/diacylglycerol pathway, is the V1 subtype.

PMID- 1348500
TI  - Thyroid autoimmunity: autoantibodies to the thyroid-stimulating hormone receptor.

PMID- 1348501
TI  - Recommendations of the International Roundtable Workshop on Bovine Spongiform
      Encephalopathy.
AB  - Recommendations of the working party were summarized as follows: Determine the
      status in all countries of their national cattle herds with respect to BSE.
      Attempt to develop a test to recognize BSE-infected animals before they become
      clinically ill. Establish procedures to prevent spread of BSE agent into the
      cattle populations, especially by eliminating feeds containing rendered ruminant
      proteins. Review the rendering processes, identify the sources and destinations
      of rendered products, and suggest appropriate changes if needed. Especially
      needed are standardized rendering procedures in regard to use of organic
      solvents, temperature, and duration of heat treatment. Review import and export
      regulations to reduce the risk of spreading BSE and to maximize opportunities for
      safe trading in cattle and cattle products. The scrapie-free certification
      program of the USDA was supported, and similar programs might be considered by
      other countries. If BSE/scrapie is diagnosed in a given country, determine
      baseline incidence of CJD in those countries and consider contributing to an
      international registry. The WHO should address the problems of BSE, formulate
      policy, participate in and coordinate research, and provide training
      opportunities for veterinary and human health care workers from eastern European
      countries and developing nations. Government and private agencies should consider
      increasing support for research on transmissibility and pathogenesis of CJD, BSE,
      CWD, scrapie, and transmissible mink encephalopathy. Prepare and publish a
      critical neuropathologic review of all spongiform encephalopathies, naturally and
      experimentally transmitted, defining the characteristics of each disease in the
      various species known to be susceptible. Consider producing guidelines for the
      biological and pharmaceutical industries with regard to sourcing, collecting, and
      processing bovine and ovine materials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348502
TI  - The effects of temperature change and transient hypoxia on auditory nerve fiber
      response in the goldfish (Carassius auratus).
AB  - Temperature change and hypoxia produce consistent, reversible effects on the
      response of single auditory nerve fibers in the goldfish. Cooling and hypoxia
      produce reductions of a cell's spontaneous activity, sensitivity, most excitatory
      or best frequency (BF) at a given signal level, and overall responsiveness to
      acoustic stimulation. Warming above ambient temperatures increases a cell's
      spontaneous activity, sensitivity, BF, and responsiveness. Adaptation, or the
      tendency for responsiveness to decline with time during a stimulus, increases
      during hypoxia and cooling, and decreases during warming. The effects of
      temperature change and hypoxia on a fiber's BF are similar to the effects of
      overall sound level. Since BF normally increases with sound level, the BF-shift
      with temperature change and hypoxia can be understood as a change in sensitivity
      or the overall effectiveness of a stimulus at a given sound level. The effects on
      neural response of temperature change and hypoxia are probably due in part to
      changes in the release and replenishment of neurotransmitter at the synapses
      between hair cells and auditory nerve fibers.

PMID- 1348503
TI  - Methylprednisolone restores sensitivity to beta-adrenergic agonists in Basenji
      Greyhound dogs.
AB  - This study investigated the effect of chronic methylprednisolone treatment on the
      ability of albuterol and aminophylline to inhibit methacholine-induced airway
      constriction in Basenji-Greyhound (BG) dogs in vivo. Pulmonary responsiveness to
      methacholine was measured in five untreated BG dogs and in the same dogs
      pretreated with albuterol or aminophylline (which has been shown in this model to
      release endogenous catecholamines). Each dog was studied before, during, and
      after daily subcutaneous methylprednisolone for 6 wk. Changes in pulmonary
      resistance and dynamic compliance with methacholine aerosol challenge were
      measured. Neither baseline pulmonary function nor pulmonary responsiveness to
      aerosolized methacholine was significantly altered by albuterol, aminophylline,
      or chronic methylprednisolone administration alone. However, pretreatment with
      albuterol or aminophylline significantly attenuated airway responses to
      methacholine in BG dogs chronically receiving methylprednisolone. Because the
      reduced sensitivity to albuterol and aminophylline was restored by chronic
      methylprednisolone treatment, we conclude that at least part of the beneficial
      effects of corticosteroids on airways in BG dogs is through modulation of beta
      adrenergic function.

PMID- 1348504
TI  - The replication of DNA containing the simian virus 40 origin by the
      monopolymerase and dipolymerase systems.
AB  - The influence of DNA polymerase (pol) alpha and DNA primase on SV40 DNA
      replication was examined in both the monopolymerase and dipolymerase systems. The
      synthesis of oligoribonucleotides in the monopolymerase and dipolymerase systems,
      followed by pulse labeling with deoxynucleoside triphosphates, yielded short
      Okazaki fragments approximately 35 nucleotides in length that were chased into
      full-length Okazaki fragments with time. In the presence of activator 1 and
      proliferating cell nuclear antigen (PCNA), but no pol delta, these short
      fragments hardly increased in size with time. DNA fragments of similar size
      (approximately 35 nucleotides) were previously observed in SV40 replication
      reactions carried out with crude extracts of HeLa cells in the presence of
      antibodies directed against PCNA (Bullock, P. A., Seo, Y.S., and Hurwitz, J.
      (1991) Mol. Cell. Biol. 11, 2350-2361). Thus, the pol alpha-primase complex
      appears to act processively for only a short distance. At high levels of pol
      alpha and primase, both short and long DNA products were formed in both systems.
      In the presence of limiting amounts of pol alpha and excess primase, the
      monopolymerase system inefficiently yielded longer length Okazaki fragments than
      those formed with excess pol alpha and primase, whereas the dipolymerase system
      yielded both short and long DNA fragments. In the presence of limiting amounts of
      primase and excess pol alpha, long products were formed in both systems, and
      virtually no short products accumulated. Thus, the ratio between the polymerase
      and primer ends available controls the size of the nascent product DNA strands.
      We examined whether PCNA, the T4 phage-encoded gene product 45 (T4 gp45), and the
      Escherichia coli beta subunit of DNA polymerase III (dnaN gene product) supported
      SV40 DNA replication and the elongation of single-stranded DNA-binding protein
      coated singly primed DNA in reactions catalyzed by pol delta, T4 DNA pol, and E.
      coli DNA pol III*, respectively. In the presence of T4 gp44/62 and T4 gp32 (but
      not human single-stranded DNA-binding protein isolated from HeLa cells), T4 DNA
      pol was weakly activated by PCNA and the beta subunit in lieu of T4 gp45 in the
      elongation of singly primed phi X174 DNA. However, the other systems were
      specific for their analogous auxiliary factors. This specificity indicates the
      importance of protein-protein interactions.

PMID- 1348505
TI  - Regulated expression of the tyrosine hydroxylase gene by membrane depolarization.
      Identification of the responsive element and possible second messengers.
AB  - Prolonged depolarization has been used as a model of adaptive changes in the
      expression of various proteins, such as ion channels and neurotransmitter
      biosynthetic enzymes, in response to increased trans-synaptic activity in the
      nervous system. In depolarized PC12 cells, tyrosine hydroxylase (TH) mRNA levels
      increased severalfold (Kilbourne, E. J., and Sabban, E. L. (1990) Mol. Brain Res.
      8, 121-127). In this study, membrane depolarization caused an increase in the
      expression of the reporter gene chloramphenicol acetyltransferase (CAT), under
      transcriptional control of the 5' region of the rat TH gene. These results
      indicate that membrane depolarization leads to increased transcription of the TH
      gene. Protein kinase C inhibitors had no effect on the induction of TH mRNA by
      depolarization, as well as the increase in formation of CAT under control of the
      upstream region of the TH gene. The depolarization responsive element in the TH
      gene was mapped to the region containing the cAMP responsive element. This region
      of the TH gene also increased CAT activity in response to the calcium ionophore,
      ionomycin. Interestingly, combined treatment with cAMP analogs and membrane
      depolarization had a greater effect than either alone on TH mRNA levels, as well
      as on CAT activity in PC12 cells transfected with the plasmid containing the cAMP
      responsive element.

PMID- 1348506
TI  - Role of sulfhydryl groups in Y2 neuropeptide Y receptor binding activity.
AB  - Benextramine, a tetramine disulfide, irreversibly inhibits neuropeptide Y (NPY)
      binding to the 50-kDa Y2 NPY receptor in bovine hippocampus (Li, W., MacDonald,
      R. G., and Hexum, T. D. (1991) Eur. J. Pharmacol. 207, 89-91). Evidence is
      presented that this inhibition occurs through a thiol-disulfide exchange.
      Treatment of bovine hippocampal membranes with benextramine inhibited NPY
      affinity cross-linking to the 50-kDa receptor. This inhibition of labeling was
      not affected by washing the membranes, but could be completely reversed by the
      addition of several thiol reducing reagents, including reduced glutathione, beta
      mercaptoethanol, and cysteine. Benextramine inhibited 70% of NPY-specific
      labeling and was much more effective than other sulfhydryl reactive agents, such
      as oxidized glutathione, cystamine, and 5,5'-dithio-bis(2-nitrobenzoic acid).
      Furthermore, the sulfhydryl-modifying agents N-ethylmaleimide and p
      chloromercuriphenyl-sulfonic acid specifically decreased NPY affinity labeling.
      Finally, NPY labeling of the 50-kDa receptor was reduced by the heavy metal ions
      Zn2+, Cu2+, and Hg2+. Preincubation with NPY prevented Y2 receptors from being
      inactivated by either 400 microM N-ethylmaleimide or 1 mM benextramine. These
      results suggest that one or more benextramine-sensitive sulfhydryl groups on the
      Y2 receptor are important for NPY binding activity.

PMID- 1348507
TI  - Modulation by NaCl of atrial natriuretic peptide receptor levels and cyclic GMP
      responsiveness to atrial natriuretic peptide of cultured vascular endothelial
      cells.
AB  - Type C atrial natriuretic peptide (ANP) receptor levels in cultured vascular
      endothelial cells were found to be very sensitive to NaCl and shown to be
      inversely related to the magnitude of ANP-induced cGMP response of the cells.
      Endothelial cells from bovine carotid artery were subcultured in Eagle's minimum
      essential medium supplemented with 10% fetal bovine serum (MEM-FBS) and in MEM
      FBS plus 25 and 50 mM NaCl. Determination, after several passages, of ANP
      receptor levels in these cells by 125I-ANP binding assay and affinity labeling
      revealed a marked reduction in the number of type C receptor in the NaCl-treated
      cells, whereas type A receptor density was not affected. RNase protection assay
      to estimate the levels of type C receptor mRNA indicated that the reduction
      occurred at a pre-translational level. In spite of the decrease in type C
      receptor number and no significant change in type A receptor (i.e. particulate
      guanylate cyclase) levels, cGMP response of the NaCl-treated cells to ANP was
      greatly exaggerated; this sensitization was also observed in membrane
      preparations. Simple masking of type C ANP receptor with C-ANF (des
      [Gln18,Ser19,Gly20,Leu21,Gly22]ANP), a ring-deleted ANP analog, did not produce
      any sensitization of the cGMP response to ANP; therefore, the above phenomenon
      cannot simply be explained by the clearance function of the type C receptor.
      Although whether the type C receptor depletion is directly related to the
      sensitization of the type A receptor/cyclase is not known, the phenomenon
      reported and characterized here will serve as a useful basis for elucidating ANP
      receptor regulation and activation.

PMID- 1348508
TI  - Structure and organization of the human transglutaminase 1 gene.
AB  - Membrane-associated transglutaminases (TGase1) have recently been found to be
      common in mammalian cells, but it is not clear whether these derive from the same
      or different genes. In order to determine the complexity of this system, we have
      isolated and characterized the human gene (TGM1). The gene of 14,133 base pairs
      was found to contain 15 exons spliced by 14 introns. Interestingly, the positions
      of these introns have been conserved in comparison with the genes of two other
      transglutaminase-like activities described in the literature, but the TGM1 gene
      is by far the smallest characterized to date because its introns are relatively
      smaller. On the other hand, the TGase1 enzyme is the largest known
      transglutaminase (about 90 kDa), apparently because its gene acquired tracts that
      encode additional sequences on its amino and carboxyl termini that confer its
      unique properties. Southern blot analyses of total human genomic DNA cut with
      several restriction enzymes reveal only one band. Use of human-rodent cell hybrid
      panels and chromosomal in situ hybridization with biotin-labeled probes revealed
      that the human TGM1 gene maps to chromosome position 14q11.2-13. Such data
      suggest there is a single gene copy per haploid human genome. Comparisons of
      sequence identities and homologies indicate that the transglutaminase family of
      genes arose by duplications and subsequent divergent evolution from a common
      ancestor but later became scattered in the human genome. Although our present
      Southern blot and chromosomal localization studies revealed no restriction
      fragment length polymorphisms, comparisons of published sequences and our genomic
      clone indicate there are two sequence variants for TGase1 within the human
      population. The rare smaller variant contains a two-nucleotide deletion near the
      5'-end, uses an alternate initiation codon, and differs from the common larger
      variant only in the first 15 amino acids. Furthermore, the DNA sequences of
      intron 14 possess several tracts of dinucleotide repeats that by polymerase chain
      reaction analysis show wide size polymorphism within the human population.
      Accordingly, this gene system constitutes a useful polymorphic marker for genetic
      linkage analyses.

PMID- 1348509
TI  - Visualization of purified fibronectin-transglutaminase complexes.
AB  - It has been reported previously (Turner, P.M., and Lorand, L. (1989) Biochemistry
      28, 628-635) that human erythrocyte transglutaminase forms a noncovalent complex
      with human plasma fibronectin near its collagen-binding domain. In the present
      study, we show by nondenaturing electrophoresis that guinea pig liver
      transglutaminase, similarly to the erythrocyte enzyme, forms a complex with human
      fibronectin. Studies of anisotropic shifts of fluorescein-labeled liver and
      erythrocyte transglutaminases, upon addition of fibronectin, indicated that both
      transglutaminases bind to fibronectin with a stoichiometry of about 2:1.
      Polymerization of fibrinogen by human erythrocyte transglutaminase was inhibited
      after complex formation with fibronectin. Complexes of fibronectin with either
      erythrocyte or liver transglutaminase were isolated by glycerol gradient zone
      sedimentation and examined by rotary shadowing electron microscopy. The globular
      transglutaminase could be readily identified binding to the thin fibronectin
      strand. The binding site for transglutaminase was within 5-10 nm of the N
      terminus of fibronectin, consistent with its proximity to the collagen-binding
      domain. Under some experimental conditions, the complex of fibronectin with
      erythrocyte transglutaminase appeared as a ring-shaped structure in which two
      transglutaminase molecules had probably dimerized. The molecular weight of the
      erythrocyte transglutaminase was determined by sedimentation equilibrium to be
      71,440 +/- 830.

PMID- 1348510
TI  - Bovine pancreatic deoxyribonuclease A. Isolation of cyanogen bromide peptides;
      complete covalent structure of the polypeptide chain.

PMID- 1348512
TI  - Diagnosis and treatment of stage fright.

PMID- 1348511
TI  - Identification of a new squamous cell differentiation marker and its suppression
      by retinoids.
AB  - Rabbit tracheobronchial epithelial cells (RbTE) can undergo squamous cell
      differentiation under defined culture conditions and, therefore, have been used
      as a model to study the regulation of squamous cell differentiation markers. In
      the present study, we identified a 20-kDa protein, designated rSQ20, in the serum
      free growth medium conditioned by RbTE cells undergoing squamous cell
      differentiation. The protein was also found in extracts of squamous
      differentiated cells. rSQ20 was labeled by cells incubated with [35S]methionine
      but not with [3H]glucosamine, suggesting that it is not a glycoprotein.
      Undifferentiated cells did not produce this protein. rSQ20 was detected in the
      conditioned medium of RbTE cells after they reached a confluent and growth
      arrested state, and thereafter its level increased markedly and concurrently with
      an increase in type I (epidermal) transglutaminase, an established marker of
      squamous cell differentiation. rSQ20 found in concentrated conditioned medium of
      squamous differentiated RbTE cells was eluted from a gel filtration column as a
      protein of 20 kDa, similar to that found by gel electrophoresis under denaturing
      conditions, suggesting that it is not a multimeric protein. A protein with an
      apparent molecular weight of 16 kDa (rSQ16), probably the product of partial
      proteolysis of rSQ20, was often found in various amounts in the conditioned
      medium of differentiated RbTE cells. beta-All-trans retinoic acid and other
      vitamin A analogues (retinoids), which suppress squamous cell differentiation,
      inhibited the expression of rSQ20 in RbTE cells. RbTE cells immortalized by
      transfection with SV40 large T antigen as well as malignantly transformed
      derivatives obtained from the immortalized cells by further transfection with v
      Ha-ras secreted SQ20 and SQ16 when grown to high cell densities although their
      squamous differentiation was impaired. An analogous protein with an apparent
      molecular weight of 16 kDa, designated hSQ16, was detected in the medium of
      differentiated normal human bronchial epithelial (NHBE) cells and normal human
      epidermal keratinocytes (NHEK). No such protein could be detected in the medium
      in which undifferentiated NHBE or NHEK cells were grown. These results suggest
      that rSQ20 and hSQ16 are new markers of squamous cell differentiation.

PMID- 1348513
TI  - Target-specific outgrowth from human mesencephalic tissue grafted to cortex or
      ventricle of immunosuppressed rats.
AB  - Human fetal mesencephalic tissue was grafted to rats with unilateral lesions of
      the nigrostriatal pathway. The animals were immunosuppressed with cyclosporine A.
      Grafts were placed either into the lateral ventricle ipsilateral to the lesion or
      in the cingulate cortex above corpus callosum. The grafts and newly formed fibers
      were visualized by immunohistochemistry with antibodies against tyrosine
      hydroxylase (TH) and the human Thy-1 glycoprotein. TH-positive fibers covered the
      total volume of striatum when the graft was placed either in the ventricle or in
      the cortex. When the transplant was located in the ventricle, TH-positive cells
      migrated from the graft into host striatum. No cell migration was seen into any
      other areas than striatum. Cortex and septum were sparsely reinnervated by the
      graft, but not to a density higher than that normally seen. Globus pallidus was
      totally devoid of TH-positive fibers. When the graft was placed in cingulate
      cortex, fiber bundles penetrated through corpus callosum into either striatum, to
      arborize in its dorsal parts, or followed the medial side of the lateral
      ventricle to ventral limbic areas, where a fiber network also was formed. Human
      specific Thy-1-immunohistochemistry revealed positivity only on the lesioned
      side. These data suggest that dopamine neurons in human mesencephalic tissue,
      grafted to the rat brain, can migrate specifically into host striatum.
      Furthermore, TH-positive fiber outgrowth occurred only into dopamine denervated
      areas of the host, avoiding areas that are normally not innervated by nigral
      neurons, but also able to reach distant target cells.

PMID- 1348514
TI  - What can we learn from studies of lymphocytes present in allergic-reaction sites?

PMID- 1348515
TI  - Late asthmatic reaction decreased after pretreatment with salbutamol and
      formoterol, a new long-acting beta 2-agonist.
AB  - The inhibitory effect of salbutamol and formoterol, a new long-acting beta 2
      agonist for inhalation, on the late asthmatic reaction (LAR), was studied in 12
      patients with allergic asthma. After a single-blind, placebo-treatment control,
      equipotent bronchodilating doses of inhaled salbutamol (500 micrograms) and
      formoterol (30 micrograms) were administered 30 minutes before bronchial allergen
      challenge in a double-blind randomized design. The early asthmatic reaction was
      completely inhibited by both drugs (p less than 0.01) but not by placebo. The LAR
      was also significantly inhibited by both drugs (p less than 0.01); formoterol was
      only slightly, but significantly, more effective than salbutamol (p = 0.04). In
      contrast to some earlier studies, the present study indicates an inhibitory
      effect of beta 2-agonists on the LAR.

PMID- 1348516
TI  - The effect of formoterol on the late asthmatic phenomena in guinea pigs.
AB  - We investigated the effects of formoterol, a new, long-acting, selective beta 2
      adrenoceptor agonist, on the antigen-induced late asthmatic response (LAR) and
      airway inflammation in guinea pigs. Animals were sensitized by exposure to
      aerosolized ovalbumin (2% in saline). After antigen challenge, preceded by
      administration of an H1-receptor antagonist, specific airway conductance was
      measured with a two-chambered whole-body plethysmograph. An aerosolized solution
      of formoterol, isoproterenol, or saline was inhaled 15 minutes before challenge.
      Bronchoalveolar lavage (BAL) was performed 24 hours after challenge. The
      provocative concentrations of histamine required to decrease specific airway
      conductance by 50% were obtained before challenge, at 24 hours, and at 72 hours
      after challenge. The LAR (52.7% +/- 7.7% of the baseline; p less than 0.02) was
      observed 6 to 8 hours after antigen challenge. An increased cellular influx in
      BAL (mainly eosinophils and macrophages) and an increased bronchial
      responsiveness to histamine occurred 24 hours after antigen challenge. Formoterol
      completely inhibited the LAR and the cellular increase in BAL; however,
      isoproterenol failed to prevent either the cellular infiltration or the LAR.
      Formoterol also decreased the antigen-induced increase in bronchial reactivity.
      These findings suggest that formoterol has inhibitory effects on the underlying
      inflammatory processes in antigen-induced asthma in addition to prolonged
      bronchodilation.

PMID- 1348517
TI  - Studies of bone marrow progenitor cells in lupus-prone mice. I. NZB marrow cells
      demonstrate increased growth in Whitlock-Witte culture and increased splenic
      colony-forming unit activity in the Thy-1-, lineage- population.
AB  - Previous studies have demonstrated that NZB marrow can transfer features of
      autoimmunity. Therefore, we undertook a study of NZB marrow to determine whether
      it demonstrated any phenotypic abnormalities. In Whitlock-Witte cultures, NZB
      marrow cells generated nonadherent cells at low seeding densities, densities at
      which marrow from other strains did not generate nonadherent cells. In contrast,
      NZB marrow grew less well than controls in Dexter cultures. Inasmuch as the
      latter favor growth of granulocyte-macrophage precursors and the former B cells,
      these results suggest a possible skewing of NZB marrow cells toward lymphocyte
      production. Unfractionated marrow cells from NZB mice were found to produce 10
      fold more splenic colonies in lethally irradiated recipients than marrow cells
      from control mice. This result was independent of the genotype of the recipient.
      When the progenitor Thy-1lo, Lin- marrow subpopulation was studied, NZB mice did
      not differ substantially from controls regarding splenic CFU. Therefore, Thy-1-,
      Lin- marrow cells were studied as a possible source of the excess splenic CFU in
      NZB mice. Indeed, the NZB Thy-1-, Lin- population contained 30-fold more splenic
      CFU than did the Thy-1-, Lin- population from control mice. These results suggest
      that NZB mice have unusual marrow progenitor cells; such cells may play a role in
      their autoimmune disease.

PMID- 1348518
TI  - Monocyte chemoattractant protein-1 regulates adhesion molecule expression and
      cytokine production in human monocytes.
AB  - Monocytes play a critical role in defending the host against foreign organisms
      and in regulating the behavior of other cells. Monocytes circulate as nonadherent
      cells in the blood and migrate as adherent cells through tissues. Adhesion
      molecules mediate not only cell adhesion, but also migration, phagocytosis, and
      many other adhesion-dependent functions. Monocyte chemoattractant protein-1 (MCP
      1) is thought to be responsible for monocyte recruitment in acute inflammatory
      conditions and may be an important mediator in chronic inflammation. In this
      study, immunofluorescence flow cytometry was used to determine whether MCP-1 can
      regulate the cell surface expression of adhesion molecules, particularly beta-2
      and alpha-4 integrins and the leukocyte adhesion molecule-1. We found that MCP-1
      induced expression of CD11c (p150,95 alpha-subunit) and CD11b (Mac-1 alpha
      subunit), and caused little or no change of CD11a (lymphocyte function-associated
      Ag-1 alpha-subunit), very late activation Ag-4, or leukocyte adhesion molecule-1.
      We demonstrated that antibodies to beta-2 and alpha-4 integrins inhibited MCP-1
      induced monocyte chemotaxis. We also showed that MCP-1 is capable of inducing IL
      1 and IL-6, but not TNF production of monocytes. These results indicate that MCP
      1 is not only a chemoattractant but also a novel cytokine with the capacity to
      regulate several parameters of monocyte function.

PMID- 1348519
TI  - Distinct T cell specificities are induced with the authentic versus recombinant
      Plasmodium berghei circumsporozoite protein.
AB  - Plasmodium berghei sporozoite (SPZ)-immune lymph node (LN) cells obtained from
      mice of different H-2 haplotypes were analyzed for the presence of
      circumsporozoite (CS) protein-reactive T cells in proliferative assays. Although
      lymphocytes from each strain responded in vitro to the priming Ag and to the
      soluble rCS protein, they did not respond to CS protein synthetic peptides.
      Parallel analysis of rCS protein-primed LN cells revealed that the two Ag are
      unequal in generating T cell specificities: although SPZ priming did not induce
      CS protein peptide-reactive T cells, priming with rCS protein did. Not being
      privy to the processing and presentation of SPZ Ag, we postulated that a
      different order of processing of the authentic, i.e., SPZ-associated CS protein
      vs soluble rCS protein might be responsible for the generation of different T
      cell specificities. Accordingly, authentic CS protein might not be processed by
      APC, or the processed fragments might obscure the recognition of smaller peptide
      fragments. Therefore, we subjected the SPZ to three cycles of a freeze/thaw
      procedure and used the denatured SPZ preparation for priming. We observed that
      contrary to priming with the authentic SPZ, denatured SPZ generated T cells
      reactive to some of the CS protein synthetic peptides. The hypothesis that each
      form of the SPZ Ag is subject to a unique Ag processing was also confirmed in
      experiments demonstrating a lack of recognition of the authentic CS protein by
      rCS protein-primed LN cells. Hence, the evidence presented in this work that
      complex protozoan Ag, such as Plasmodia, might present different requirements for
      Ag-specific T cell induction/activation not only enhances the basic understanding
      of the immune system, but is essential for the development of antimalaria
      vaccine(s). In addition, these observations support the hypothesis that the
      molecular context of the priming Ag influences the outcome of T cell
      specificities, by providing evidence that the authentic CS protein induces a T
      cell repertoire that is distinct from that induced by the rCS protein.

PMID- 1348520
TI  - CD28-stimulated IL-2 gene expression in Jurkat T cells occurs in part
      transcriptionally and is cyclosporine-A sensitive.
AB  - CD28 is a glycoprotein expressed as a homodimer on the surface of a major subset
      of human T cells. Previous studies have shown that proliferation of peripheral
      blood T cells involving the CD28 pathway is associated with cyclosporine A (CsA)
      resistant IL-2 gene expression. This pathway was shown to specifically regulate
      the stability of mRNA for several lymphokines including IL-2. We have
      investigated the expression of the IL-2 gene in the Jurkat cell line, J32 clone,
      induced by CD28 stimulation. Cross-linked anti-CD28 mAb alone was sufficient to
      induce the release of small amounts of IL-2 (256 U/ml). The CD28-mediated IL-2
      release was enhanced with simultaneous engagement of CD28 and CD2 or CD28 and CD3
      molecules. Hybrid constructs in which the human IL-2 gene 5' flanking region
      drives luciferase expression (pIL-2-Luc) were used to help delineate whether the
      CD28 pathway activates the IL-2 gene transcriptionally. Costimulation of cells
      with CD28 mAb and either PHA or CD2 mAb induced a 20- to 90-fold increase in the
      expression of pIL-2-Luc as well as IL-2 release. Costimulation with CD28 mAb plus
      PMA gave only five- to sevenfold increase in enhancer activity. In contrast, no
      enhancer activity was detected after stimulation with CD28 or CD2 mAb alone. Both
      IL-2 release and pIL-2-Luc activity were inhibited by CsA in J32 cells. The
      degree of CsA inhibition was concentration dependent and was similar in cells
      stimulated with either CD28 mAb or CD3 mAb. Maximum inhibition was achieved with
      1 microgram/ml of CsA. Studies with internal deletion mutations of the IL-2 gene
      5' flanking sequence revealed that as with stimulation through the TCR pathway,
      the CD28 pathway requires 5' flanking sequences located within 500 bp of the
      transcription start site. These results are the first direct evidence that the
      triggering of CD28 molecule is sufficient to induce IL-2 release in J32 cells.
      Furthermore these studies strongly indicate that IL-2 gene expression induced by
      CD28 stimulation occurs, in part, transcriptionally and is CsA sensitive in these
      cells.

PMID- 1348521
TI  - Cellular mechanisms of the antitumor activity of recombinant IL-6 in mice.
AB  - The systemic administration of human rIL-6 to mice resulted in the regression of
      established, 3-day pulmonary micrometastases from two weakly immunogenic tumors,
      but not from a nonimmunogenic tumor, in the absence of observable toxicity.
      Although IL-6 alone failed to have a significant therapeutic impact on advanced,
      10-day pulmonary macrometastases from weakly immunogenic tumors, substantial cure
      rates of mice could be achieved when this cytokine was combined with
      cyclophosphamide. Histologic analysis of the lungs of mice receiving IL-6
      revealed infiltration with lymphoid cells during the regression of pulmonary
      nodules from a weakly immunogenic tumor. IL-6-mediated tumor regression could be
      abrogated after selective in vivo depletion of either CD4 or CD8 T cell subsets
      by the systemic administration of specific mAb. In vivo generation of tumor
      specific CTL, but not of lymphokine-activated killer cells, was detected in the
      lungs of IL-6-treated mice during regression of pulmonary metastases.
      Collectively, these findings demonstrate a role for IL-6 in the treatment of
      established solid tumors that have the capacity to elicit T cell responses in the
      host. Differences in host cellular mechanisms involved in tumor regression
      mediated by immunotherapy using IL-6 vs IL-2 are discussed.

PMID- 1348522
TI  - Excitatory transmitter amino acid release from the ischemic rat cerebral cortex:
      effects of adenosine receptor agonists and antagonists.
AB  - The effects of selective adenosine receptor agonists [N6-cyclopentyladenosine
      (CPA) and N-ethylcarboxamidoadenosine (NECA)] and antagonists [8-cyclopentyl-1,3
      dipropylxanthine (DPCPX) and 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4
      triazolo[1,5-c]quinazoline-5-im ine (CGS-15943A)] on aspartate and glutamate
      release from the ischemic rat cerebral cortex were studied with the cortical cup
      technique. Cerebral ischemia (for 20 min) was elicited by four-vessel occlusion.
      Excitatory amino acid releases were compared from control ischemic rats and drug
      treated rats. Basal levels of aspartate and glutamate release were not greatly
      affected by pretreatment with the adenosine receptor agonists or antagonists.
      However, CPA (10(-10) M) and NECA (10(-9) M) significantly inhibited the ischemia
      evoked release of aspartate and glutamate into cortical superfusates. The ability
      to block ischemia-evoked release of excitatory amino acids was not evident at
      higher concentrations of CPA (10(-6) M) or NECA (10(-5) M). The selective A1
      receptor antagonist DPCPX also had no effect on release when administered at a
      low dosage (0.01 mg/kg, i.p.) but blocked the ischemia-evoked release of
      aspartate and glutamate at a higher dosage (0.1 mg/kg). Evoked release was
      inhibited by the selective A2 receptor antagonist CGS-15943A (0.1 mg/kg, i.p.).
      Thus, adenosine and its analogs may suppress ischemia-evoked release of
      excitatory neurotransmitter amino acids via high-affinity A1 receptors, whereas
      coactivation of lower-affinity A2 receptors may block (or reverse) the A1
      mediated response.

PMID- 1348523
TI  - Dopaminergic modulation of glutamate release in striatum as measured by
      microdialysis.
AB  - Glutamate and aspartate are the primary neurotransmitters of projections from
      motor and premotor cortices to the striatum. Release of glutamate may be
      modulated by dopamine receptors located on corticostriatal terminals. The present
      study used microdialysis to investigate the dopaminergic modulation of in vivo
      striatal glutamate and aspartate release in the striatum of awake-behaving rats.
      Local perfusion with a depolarizing concentration of K+ through a dialysis probe
      into the rat striatum produced a significant increase in the release of
      glutamate, aspartate, and taurine. The D2 agonist LY171555 blocked the K(+)
      induced release of glutamate and aspartate, but not taurine, in a concentration
      dependent manner. The D1 agonist SKF 38393 did not alter K(+)-induced release of
      glutamate and taurine, but did significantly decrease aspartate release. Neither
      agonist had any effect on basal amino acid release. The D2 antagonist (-)
      sulpiride reversed the inhibitory effects of LY 171555 on K(+)-induced glutamate
      release. These results provide in vivo evidence for a functional interaction
      between dopamine, the D2 receptor, and striatal glutamate release.

PMID- 1348524
TI  - N-methyl-D-aspartate antagonists block fos-like protein expression induced via
      multiple signaling pathways in cultured cortical neurons.
AB  - c-fos mRNA and Fos-like protein(s) (FLP) are induced in cultured cortical neurons
      by glutamate, high K+, phorbol ester, basic fibroblast growth factor, Zn2+, and
      vasoactive intestinal peptide. Glutamate induction of c-fos mRNA and FLP is
      blocked by noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK-801, and
      competitive NMDA antagonists, 4-(3-phosphonopropyl)piperazin-2-carboxylic acid
      and 2-amino-7-phosphonoheptanoate. These antagonists partially block high K(+)-,
      phorbol ester-, Zn(2+)-, and VIP-induced c-fos mRNA expression, but have no
      effect on bFGF-induced c-fos mRNA expression. However, both competitive and
      noncompetitive NMDA antagonists completely block FLP induction by all of these
      agents without affecting total protein synthesis. Therefore, these NMDA
      antagonists block FLP translation, without blocking c-fos transcription. It is
      hypothesized that NMDA receptor activation is required for translation of c-fos
      mRNA in cortical neurons after stimulation of multiple intracellular signaling
      pathways. It is possible that NMDA antagonists prevent cortical plasticity by
      blocking induction of the Fos protein that would normally be induced by
      neurotrophic factors, neurotransmitters, and neuromodulators.

PMID- 1348525
TI  - Glutamate metabolism in rat cortical astrocyte cultures.
AB  - Glutamate metabolism in rat cortical astrocyte cultures was studied to evaluate
      the relative rates of flux of glutamate carbon through oxidative pathways and
      through glutamine synthetase (GS). Rates of 14CO2 production from [1
      14C]glutamate were determined, as was the metabolic fate of [14C(U)]glutamate in
      the presence and absence of the transaminase inhibitor aminooxyacetic acid and of
      methionine sulfoximine, an irreversible inhibitor of GS. The effects of
      subculturing and dibutyryl cyclic AMP treatment of astrocytes on these parameters
      were also examined. The vast majority of exogenously added glutamate was
      converted to glutamine and exported into the extracellular medium. Inhibition of
      GS led to a sustained and greatly elevated intracellular glutamate level, thereby
      demonstrating the predominance of this pathway in the astrocytic metabolism of
      glutamate. Nevertheless, there was some glutamate oxidation in the astrocyte
      culture, as evidenced by aspartate production and labeling of intracellular
      aspartate pools. Inhibition of aspartate aminotransferase caused a greater than
      70% decrease in 14CO2 production from [1-14C]glutamate. Inhibition of GS caused
      an increase in aspartate production. It is concluded that transamination of
      glutamate rather than oxidative deamination catalyzed by glutamate dehydrogenase
      is the first step in the entry of glutamate carbon into the citric acid cycle in
      cultured astrocytes. This scheme of glutamate metabolism was not qualitatively
      altered by subculturing or by treatment of the cultures with dibutyryl cyclic
      AMP.

PMID- 1348526
TI  - Astrocyte heterogeneity: endogenous amino acid levels and release evoked by non-N
      methyl-D-aspartate receptor agonists and by potassium-induced swelling in type-1
      and type-2 astrocytes.
AB  - The aim of the present study was to determine whether endogenous amino acids are
      released from type-1 and type-2 astrocytes following non-N-methyl-D-aspartate
      (NMDA) receptor activation and whether such release is related to cell swelling.
      Amino acid levels and release were measured by HPLC in secondary cultures from
      neonatal rat cortex, highly enriched in type-1 or type-2 astrocytes. The
      following observations were made. (a) The endogenous level of several amino acids
      (glutamate, alanine, glutamine, asparagine, taurine, serine, and threonine) was
      substantially higher in type-1 than in type-2 astrocytes. (b) The spontaneous
      release of glutamine and taurine was higher in type-1 than in type-2 astrocytes;
      that of other amino acids was similar. (c) Exposure of type-2 astrocyte cultures
      to 50 microM kainate or quisqualate doubled the release of glutamate and caused a
      lower, but significant increase in that of aspartate, glycine, taurine, alanine,
      serine (only in the case of kainate), and glutamine (only in the case of
      quisqualate). These effects were reversed by the antagonist CNQX. (d) Exposure of
      type-1 astrocyte cultures to 50-200 microM kainate or 50 microM quisqualate did
      not affect endogenous amino acid release, even after treating the cultures with
      dibutyryl cyclic AMP. (e) Exposure of type-1 or type-2 astrocyte cultures to 50
      mM KCl (replacing an equimolar concentration of NaCl) enhanced the release of
      taurine greater than glutamate greater than aspartate. The effect was somewhat
      more pronounced in type-2 than in type-1 astrocytes. Veratridine (50 microM) did
      not cause any increase in amino acid release. (f) The release of amino acids
      induced by high [K+] appeared to be related to cell swelling, in both type-1 and
      type-2 astrocytes. Swelling and K(+)-induced release were somewhat higher in type
      2 than in type-1 astrocytes. In contrast, neither kainate nor quisqualate caused
      any appreciable increase in cell volume. It is concluded that non-NMDA receptor
      agonists stimulate the release of several endogenous amino acids (some of which
      are neuroactive) from type-2 but not from type-1 astrocytes. The effect does not
      seem to be related to cell swelling, which causes a different release profile in
      both type-1 and type-2 astrocytes. The absence of kainate- and quisqualate-evoked
      release in type-1 astrocytes suggests that the density of non-NMDA receptors in
      this cell type is very low.

PMID- 1348527
TI  - 1-Aminocyclopentane-trans-1,3-dicarboxylic acid induces glutamine synthetase
      activity in cultured astrocytes.
AB  - In this study we have investigated the effect of excitatory amino acids on the
      activity of glutamine synthetase, a glial-specific enzyme that plays a key role
      in the regulation of glutamate concentration in the CNS. We found that of L
      glutamate, N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate, kainate, and 1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans
      ACPD), only the metabotropic glutamate receptor agonist trans-ACPD had an effect
      on glutamine synthetase specific activity in cultures of rat type I cortical
      astrocytes. Exposure of astrocytes to 1.0 mM trans-ACPD for 24 h resulted in an
      increase in glutamine synthetase activity to 149 +/- 11% of that in control
      cultures. This effect was concentration dependent, stereoselective, and blocked
      by cycloheximide. In addition, the increase in glutamine synthetase activity
      occurred at lower concentrations of trans-ACPD that did not produce morphological
      alterations or lysis of the astrocytes as measured by the lactate dehydrogenase
      content. These findings are consistent with the hypothesis that activation of the
      metabotropic excitatory amino acid receptor in astrocytes is coupled to the
      regulation of an enzyme essential to the metabolism and recycling of the
      excitatory transmitter L-glutamate.

PMID- 1348528
TI  - Detection of migrated allogeneic oligodendrocytes throughout the central nervous
      system of the galactocerebrosidase-deficient twitcher mouse.
AB  - Galactocerebrosidase-deficient oligodendrocytes of 'twitcher' (twi/twi) mice
      degenerate prematurely. Transplantation of normal bone marrow cells has been
      shown to alleviate symptoms and to prolong survival time. However, characteristic
      ataxia ('twitching') is not cured. In an attempt to improve further the condition
      of twitcher mice, allogeneic foetal liver cells were transplanted as a source of
      normal haemopoietic stem cells and supplemented with intracerebral
      transplantation of foetal brain cells. A reliable method was developed to detect
      donor-type cells in brain tissue. Bacteriophage lambda transgenic foetal mice
      were used as donors of both foetal liver and brain cells. Integrated copies of
      lambda DNA in donor cells were detected by in situ hybridization with
      biotinylated probes, which were then stained using streptavidin alkaline
      phosphatase. This technique was combined with immunohistochemistry to distinguish
      donor-type oligodendrocytes from macrophages. Immunoperoxidase staining with an
      antiserum to carbonic anhydrase-II produced dark perikarya of oligodendrocytes.
      The results demonstrated that local foetal brain cell grafts resulted in a wide
      dissemination of donor-type oligodendrocytes throughout the twitcher brain. The
      addition of a foetal brain cell graft to haemopoietic cell transplantation
      resulted in significantly prolonged survival of twitcher mice.

PMID- 1348529
TI  - Expression of LFA-1/ICAM-1 in CNS lymphomas: possible mechanism for lymphoma
      homing into the brain.
AB  - We examined a possible role for the adhesion molecules LFA-1 and ICAM-1 in
      localizing central nervous system non-Hodgkin's lymphomas (CNS-NHLs) to the
      brain. Fresh frozen sections from 12 monoclonal CNS NHLs (11 primary, one
      secondary) were stained with monoclonal antibodies to LFA-1 alpha chain (CD11a),
      beta chain (CD18) and, ICAM-1 (CD54). Additional staining made use of rat
      monoclonal antibodies to the human and mouse high endothelial venule antigens
      HECA 452 and MECA 79 and mouse ICAM-1. The expression of these same molecules was
      also studied in mice with severe combined immunodeficiency (SCID) mice, bearing
      intracranial human lymphoblastoid cells. Eleven of the CNS-NHL tumors expressed
      LFA-1 alpha (one strongly, one intermediate, nine weakly). Nine of the tumors
      weakly expressed LFA-1 beta.. Nine of twelve tumors weakly expressed ICAM-1. In
      six of seven tumors definite blood vessels stained for ICAM-1. Non-tumor brain
      from two patients and non-tumor cerebral blood vessels showed no staining with
      CD11a, CD18 or CD54 antibodies. Strong expression of LFA-alpha and LFA-beta as
      well as ICAM-1 was noted in human lymphoblastoid cells (LCLs)/SCID mouse CNS
      lymphomas. Tumor blood vessels in these mice stained for mouse ICAM-1. Normal
      SCID mouse brains showed no staining with CD11a, CD18, CD54 or mouse ICAM-1
      antibodies. Human, human/mouse CNS lymphomas, normal human, and mouse brains
      showed no staining with either HECA 452 or MECA 79.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1348531
TI  - Abstracts presented at the 1991 Clinical Conference and Exposition of the
      National Perinatal Association. Boston, Massachusetts, November 7-10, 1991.

PMID- 1348530
TI  - Subcutaneous tocolytic infusion therapy for patients at very high risk for
      preterm birth.
AB  - Patients with multiple gestations or recalcitrant preterm labor are at very high
      risk for preterm birth in spite of adequate tocolysis. Subcutaneous infusion of
      tocolytic medications on an ambulatory basis has been used in several small
      series and has effectively prolonged gestation. This retrospective analysis
      presents data from 992 patients at very high risk for preterm delivery who were
      prescribed this therapy. The amount of tocolytic medication was individualized by
      utilizing the patient's volume of distribution and clearance. Pharmacists
      adjusted the dosage based on uterine activity strips received by nursing
      personnel. The average basal rate was .073 +/- .020 mg/h. Patients received an
      average of seven scheduled boluses per day and 1.54 +/- .93 unscheduled boluses
      per week (.25 +/- .03 mg each). The therapy extended the gestation a mean of 38
      +/- 23 days and average gestational age at delivery was 36.3 +/- 2.6 weeks with a
      mean birthweight of 2759 +/- 681 g. This study, utilizing a large number of
      patients, confirms earlier reports that for women at very high risk for preterm
      delivery subcutaneous tocolytic infusion therapy is beneficial. Prospective
      studies evaluating such treatment on a randomized basis are indicated.

PMID- 1348532
TI  - A comparison of proliferating cell nuclear antigen (PCNA) immunostaining,
      nucleolar organizer region (AgNOR) staining, and histological grading in
      gastrointestinal stromal tumours.
AB  - Gastrointestinal stromal tumours are lesions in which it is difficult to predict
      clinical outcome from the histological appearances. Sixty cases were studied
      using three different methods of assessing aspects of cellular proliferation;
      these were (i) immunostaining for proliferating cell nuclear antigen (PCNA), (ii)
      interphase nucleolar organizer region staining (AgNORs), and (iii) a histological
      grading system based on mitotic counts. Both PCNA immunostaining and AgNOR counts
      were found to correlate well with histological grading and all three methods
      independently showed good correlations with survival. This suggests that these
      proliferation-associated markers may be used as additional features to support
      histological grading in this relatively uncommon group of tumours.

PMID- 1348533
TI  - Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in
      infant formulas.
AB  - The fatty acid composition of erythrocyte total lipids taken from a group of term
      infants 10 weeks after being fed a commercial infant formula with a high ratio of
      linoleic acid (18:2n-6) (LA) to alpha-linolenic acid (18:3n-3) (ALA) (19:1; LA,
      14%; ALA, 0.7%; group A, n = 10) was compared with the fatty acid composition of
      erythrocytes from infants fed formulas that contained LA/ALA ratios reduced by
      either increasing ALA (4:1; LA, 13%; ALA, 3.3%; group B, n = 11) or decreasing LA
      (3:1; LA, 3.5%; ALA, 1.1%; group C, n = 8). Results were compared with those in
      an age-controlled group (n = 9) of breast-fed infants. Decreasing the LA/ALA
      ratio increased n-3 C20 and C22 fatty acid incorporation (formula B = 8.98% +/-
      0.65%; formula C = 9.30% +/- 0.95%) relative to formula A (5.97% +/- 0.76%; p
      less than 0.05). Although docosahexaenoic acid (22:6n-3) (DHA) incorporation was
      highest in infants fed formulas B and C (4.78% +/- 0.45% and 4.48% +/- 0.49%,
      respectively) relative to formula A (3.47% +/- 0.46%; p less than 0.05), it did
      not reach levels found in breast-fed infants (6.55% +/- 1.23%; p less than 0.05).
      In addition, levels of arachidonic acid (20:4n-6) (AA) were lower in all formula
      fed groups (p less than 0.05) relative to those in breast-fed infants. Based on
      some equations, it is predicted that AA levels in tissues of infants fed lower
      LA/ALA ratios would be reduced even further. Because both AA and DHA are probably
      essential for normal neural development of the infant, formulas with LA/ALA
      ratios below 4:1 are likely to result in fatty acid profiles notably different
      from those of breast-fed infants.

PMID- 1348534
TI  - Lipids in infant nutrition. Proceedings of the Mead Johnson Symposium. August 29
      30, 1991.

PMID- 1348535
TI  - Immune serum markers and CD4 cell counts in HIV-infected intravenous drug users.
AB  - We examined the association of three serum immune markers with CD4 cell counts in
      a large cohort of i.v. drug users with and without human immunodeficiency virus
      (HIV) infection. Levels of beta 2-microglobulin and neopterin were significantly
      elevated in HIV-infected subjects and increased in association with decline in
      CD4 cell counts (all p less than 0.001). Serum IgA levels in HIV-seropositive
      individuals were significantly elevated only when the CD4 cell count was less
      than 200/microliters (p less than 0.001). After controlling for HIV status and
      CD4 count, recent history of hepatitis was associated with significantly higher
      beta 2-microglobulin (p = 0.028) and marginally higher neopterin (p = 0.052)
      levels. There was no association of race, gender, or drug use patterns with
      levels of serum immune markers after controlling for HIV status and CD4 count.
      These data indicate that immune activation is coupled with immunosuppression in
      HIV-infected i.v. drug users. In addition, beta 2-microglobulin and neopterin
      levels are elevated in persons with a recent history of hepatitis but not in
      those with recent non-AIDS-defining bacterial infections. Markers of immune
      activation do not vary by race, gender, or drug use patterns among i.v. drug
      users.

PMID- 1348536
TI  - Sequestration of organic cations by acidified hepatic endocytic vesicles and
      implications for biliary excretion.
AB  - A number of cationic amine drugs that are taken up by liver and excreted into
      bile may accumulate in acidified intracellular organelles such as lysosomes and
      endosomes. These studies were undertaken to assess directly the uptake and
      accumulation of three types of model organic cationic amines by endocytic
      vesicles, and the role of vesicle acidification in this process. Uptake of
      tubocurarine (TC), vecuronium and tributylmethylammonium (TBuMA) by purified rat
      liver multivesicular bodies (MVB) (prelysosomal endocytic vesicles) was dependent
      upon MgATP, time and drug concentration. After 60 min, 52 to 81% of MVB cation
      content was dependent upon vesicle acidification (due to an electrogenic proton
      pump), but not upon an interior positive vesicle membrane potential. Nineteen to
      42% of MVB cation content appeared due to binding to MVB membranes or to internal
      lipoproteins. Vesicle-to-medium ATP-dependent apparent concentration ratios for
      these three cations were 3.3 to 51. MVB uptake of these cations resembled uptake
      of methylamine, a tertiary amine known to distribute across organellar membranes
      according to pH gradients. By contrast, MVB uptake of the lipophilic quaternary
      amine methyldeptropine was not dependent upon MgATP or on development of MVB pH
      or membrane potential gradients. In further studies, TC, vecuronium and TBuMA
      were rapidly taken up by the isolated perfused rat liver and excreted in bile.
      Exposure to 250 mciroM primaquin (which partially alkalinized acidic endosomes
      and lysosomes) reduced accumulation of [3H]vecuronium in a lysosomal fraction by
      23%, decreased perfusate disappearance of TC and TBuMA, but not of vecuronium,
      and decreased biliary appearance of all three cations. These studies suggest that
      acidified intracellular organelles sequester certain organic cationic drugs,
      possibly via a drug/proton antiporter, and/or diffusion followed by
      intravesicular protonation and trapping of tertiary amines. However, attempts at
      partial displacement of these drugs, accomplished through partial vesicle
      alkalization by primaquin, decreased excretion of TC, vecuronium and TBuMA,
      perhaps reflecting the small functional size of the displaceable organellar drug
      compartment and/or competition between primaquin and the organic cations for
      membrane transport processes.

PMID- 1348537
TI  - Naloxone and norbinaltorphimine administered intracerebroventricularly antagonize
      spinal morphine-induced antinociception in mice through the antianalgesic action
      of spinal dynorphin A (1-17).
AB  - Previously, a number of analgesic agonists, when administered i.c.v. to mice,
      were shown putatively to activate the release of dynorphin A (1-17) (Dyn A) in
      the spinal cord. Whether released endogenously or administered i.t., Dyn A
      produces an antianalgesic action against i.t. administered morphine. In the
      present study, the opioid antagonists, naloxone and norbinaltorphimine (N-BNI),
      were shown to activate the Dyn A system. Intracerebro-ventricular administration
      of both naloxone and N-BNI antagonized the antinociceptive effect of i.t.
      morphine in the mouse tail-flick test, an effect designated as an antianalgesic
      action. This antianalgesic action was demonstrated to be mediated by spinal Dyn A
      in the following ways: 1) the antagonistic effect of i.c.v. naloxone and N-BNI
      was eliminated by administration of small doses of i.t. naloxone and N-BNI, a
      unique situation where administration of the opioid antagonists at a second
      (i.t.) site reversed the antagonistic effect of opioid antagonists administered
      at the other (i.c.v.) site; 2) i.t. pretreatment with dynorphin antiserum
      prevented the antianalgesic effect; 3) morphine pretreatment (s.c., 10 mg/kg),
      which produces desensitization to the effect of spinal Dyn A, eliminated the
      antianalgesic effect; and 4) pretreatment with i.c.v. naloxone (3 hours) and N
      BNI (24 hours) which presumably releases Dyn A produced desensitization to the
      antagonistic effect of i.c.v. naloxone and N-BNI as well as to the antianalgesic
      action of i.t. Dyn A. Taken together, the results indicate that both i.c.v.
      naloxone and N-BNI produced indirect antagonistic actions which were mediated at
      the spinal cord by the antianalgesic action of Dyn A.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1348538
TI  - Effect of cyclosporine on colchicine secretion by the kidney multidrug
      transporter studied in vivo.
AB  - The multidrug resistance (MDR) transport protein is a normal constituent of
      proximal renal tubules although its function has not been defined in vivo. We
      find that colchicine, an MDR substrate, is secreted into urine by a process which
      is distinct from the organic cation transporter responsible for
      tetraethylammonium and N-methylnicotinamide secretion. Cyclosporine (CsA), which
      reverses MDR in vitro presumably by inhibiting the MDR transporter, inhibits
      colchicine renal secretion but does not inhibit the net secretion of the organic
      cation, ranitidine, or the organic anion, p-aminohippurate. After CsA (2 mg/kg
      i.v.), colchicine renal clearance decreased from 6.23 +/- 0.46 to 3.58 +/- 0.31
      ml/min.kg (P less than .05), glomerular filtration rate was unchanged (4.21 +/-
      0.08 and 3.88 +/- 0.17 ml/min.kg, before and after CsA, respectively; P = .09)
      and colchicine secretory ratio decreased from 1.48 +/- 0.11 to 0.92 +/- 0.07 (P
      less than .05). Cremophor (CsA vehicle) increased colchicine renal clearance
      (6.77 +/- 0.29 to 7.7 +/- 0.3 ml/min.kg, P less than .05) and colchicine
      secretory ratio (1.425 +/- 0.071 to 1.621 +/- 0.061, P less than .05). The
      inhibition of colchicine secretion was long-lived lasting at least 30 hr after
      CsA. Thus, colchicine is actively secreted into urine by the multidrug
      transporter in vivo. CsA profoundly inhibits colchicine secretion into urine
      while having no effect on the secretion of the organic cation ranitidine or the
      organic anion p-aminohippurate.

PMID- 1348539
TI  - A further evaluation of the effects of K+ depolarization on glutamate-evoked
      [3H]dopamine release from striatal slices.
AB  - Exogenous glutamate will evoke dopamine (DA) release from striatal slices in
      vitro. To further characterize glutamate-evoked DA release from striatal slices,
      experiments were designed to: 1) determine if sufficient endogenous glutamate can
      be released in vitro to presynaptically mediate [3H]DA release in the absence of
      Mg++ and 2) reevaluate how K+ depolarization affects glutamate-evoked [3H]DA
      release. Removal of Mg++ to potentiate N-methyl-D-aspartate (NMDA) receptor
      mediated DA release increased 15 mM K(+)-evoked [3H]DA release to about 200% of
      control. The potentiation of this release was probably not mediated by NMDA
      receptors because it was not blocked by the glutamate receptor antagonists MK
      801, 6,7-dinitroquinoxalinedione (DNQX) or kynurenate. Furthermore, the removal
      of Mg++ increased DA release substantially (200%) in the presence of 5 microM
      sulpiride and 10 microM nomifensine, indicating that DA reuptake and DA D2
      autoreceptors are not primarily responsible for increased DA release. In the
      absence of Mg++, depolarization produced by 20 mM or greater [K+] inhibited DA
      released by exogenous glutamate, whereas a much higher [K+] was necessary to
      evoke endogenous glutamate release. In the presence of 1.5 mM Mg++, a reduction
      of the "Mg++ blockade" of NMDA receptors by 15 mM K+ depolarization during
      glutamate-evoked DA release was evaluated with and without the DA reuptake
      inhibitor nomifensine and the DA D2 antagonist sulpiride. DA released by K+
      depolarization (Mg++ present) was markedly increased by 1 mM glutamate, but this
      effect was only partially reversed by kynurenate or high concentrations of either
      MK-801 (25 microM) or DNQX (100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348540
TI  - Transkinetoplastidy--a novel phenomenon involving bulk alterations of
      mitochondrion-kinetoplast DNA of a trypanosomatid protozoan.
AB  - Dramatic and consistent changes of mitochondria or kinetoplast DNA (kDNA) were
      observed in certain variants of Leishmania amazonensis (A variants) selected in
      vitro for arsenite-resistance. This was found initially by comparing different
      lots of wild-type cells and their respective A variants resistant to 30 microM
      arsenite. The kDNAs isolated from these two groups had different restriction
      patterns and hybridized poorly to each other, whereas those from different lots
      within each of the two groups were identical. Hybridization data showed an
      overall identity of less than 10(-3) between total kDNAs of the two groups. This
      difference was further examined in three independent series of variants, which
      were selected from three different clones for resistance to graded concentrations
      of arsenite (5-50 microM). In all three series, their kDNAs were found to change
      abruptly in an identical pattern at a late step of the selection process, i.e., A
      variants resistant to 15 microM or 30 microM arsenite. There was no apparent loss
      of kDNA in the process. Most of the changes observed appear to involve a shift in
      either the dominance or the copy number of different minicircle subclasses.
      Surprisingly, the kDNAs of tunicamycin-resistant variants (T variants) were also
      found to undergo similar changes. Genetic changes previously described in both A
      and T variants are limited to their nuclei. Namely, different chromosomal regions
      are amplified to produce large DNA circles which are responsible for the drug
      resistant phenotypes. Interestingly, other arsenite-resistant clones without such
      chromosomal DNA amplification (A' variants) had kDNA of the wild-type pattern.
      The profound changes of kDNA observed are unprecedented. We propose the term
      "transkinetoplastidy" for this phenomenon to distinguish it from
      dyskinetoplastidy or the loss of kDNA described previously in trypanosomatid
      protozoa. This phenomenon is discussed with respect to the possible mechanisms of
      its generation, regulation and relation to the drug-resistant phenotypes.

PMID- 1348541
TI  - Ultrastructure of Tricornia muhezae N. G., n. sp. (Microspora, Thelohaniidae), a
      parasite of Mansonia africana (Diptera: Culicidae) from Tanzania.
AB  - Collections of Mansonia africana mosquito larvae were made at one site in N.E.
      Tanzania in 1985 and 1987 and from two additional sites, both within about 2 mi
      of the original one in 1987. An octosporous microsporidian, present at all three
      sites, was found in both years infecting from 7 to 22% of larvae. Spores (stained
      in Giemsa) measured 3.0 microns +/- 0.25 microns x 2.25 microns +/- 0.26 microns.
      Ultrastructurally, spores were seen to have an anterior rim surrounding a
      depressed area where the endospore was at its thinnest. In transmission electron
      microscopy section, the rim appeared as two processes into which all layers of
      the wall extended. At the posterior end all layers of the wall extended into a
      simple knob-like structure which could be interpreted as a section through a
      crest running longitudinally around the spore. The polar filament was anisofilar,
      with two anterior coils of greater diameter than the three posterior coils.
      Although most closely resembling the genera Amblyspora and Parathelohania in the
      family Thelohaniidae, the species in M. africana differs from the former, which
      has oval spores, broadly rounded at the ends, and from the latter, which has a
      prominent, ridged posterior extension to the spores. The new species has been
      placed in a new genus and the name Tricornia muhezae proposed.

PMID- 1348542
TI  - Potent and systemically active aminopeptidase N inhibitors designed from active
      site investigation.
AB  - Derivatives of amino acids bearing various zinc-coordinating moieties (SH, COOH,
      CONHOH, and PO3H2) were synthesized and tested for their ability to inhibit
      aminopeptidase N (APN). Among them, beta-amino thiols were found to be the most
      efficient with IC50's in the 11-50 nM range. These results suggest that the S1
      subsite of APN is a deep but not very large hydrophobic pocket, optimally fitting
      side chains of moderate bulk endowed with some degree of freedom. The iv
      administration of the inhibitors, alone, did not induce antinociceptive responses
      on the hot plate test in mice. However, in presence of 10 mg/kg acetorphan, a
      prodrug of the neutral endopeptidase inhibitor thiorphan, these compounds gave a
      large increase in the jump latency time with ED50's of 2 and 2.4 mg/kg for the
      disulfides of methioninethiol H2NCH(CH2CH2SCH3)CH2S]2 and S-oxomethioninethiol
      [H2NCH(CH2CH2S(O)CH3)CH2S]2, respectively. These results show that the disulfide
      forms of beta-amino thiols are efficient prodrugs of aminopeptidase N inhibitors
      capable of crossing the blood-brain barrier.

PMID- 1348543
TI  - The significance of low density microfilaraemia in the transmission of lymphatic
      filarial parasites.
AB  - Low density microfilaraemia (mf) is a density of circulating mf which is often
      undetected by standard survey techniques; it occurs naturally, after anti
      filarial drug administration and after vector control. Its occurrence in human
      populations is closely related to the observed mf frequency distributions in
      them, and it is an important cause of underestimation of mf prevalence rates in
      epidemiological surveys. In the present paper it is defined quantitatively as a
      count of less than 4 mf 20 microliters-1 of capillary blood or less than 30 mf ml
      1 of venous blood. Detection of low intensity transmission of parasites is
      difficult; detection by clinical, entomological or immunological methods may be
      more sensitive than the usually employed parasitological techniques, due to the
      extreme inefficiency of the transmission process. Mosquito vectors of filariasis
      ingest and develop low density mf readily; since they exhibit limitation or
      proportionality, Aedes, Culex and Mansonia spp. vectors do this more efficiently
      than Anopheles spp. which exhibit facilitation. Field studies indicate that low
      level microfilaraemia can initiate a resumption of transmission after very
      efficient control programmes where Aedes spp. are vectors, whereas eradication
      has been achieved in areas of Anopheles transmission by levels of vector control
      which fall far short of eradicating malaria. The situation in the extensive
      endemic areas where Culex spp. are vectors is less clear, and should be a
      research priority.

PMID- 1348544
TI  - ts1, a temperature-sensitive mutant of Moloney murine leukemia virus TB, can
      infect both CD4+ and CD8+ T cells but requires CD4+ T cells in order to cause
      paralysis and immunodeficiency.
AB  - When neonatal FVB/N mice were inoculated with ts1, a temperature-sensitive mutant
      of Moloney murine leukemia virus TB, they developed a progressive bilateral
      hindlimb paralysis and immunodeficiency leading to death 4 to 6 weeks after
      inoculation. T lymphocytes have been shown to be primarily responsible for this
      ts1-induced syndrome. Here we compare the role played by each subset of T
      lymphocytes, i.e., CD4+ and CD8+ T cells, in disease development. Mice were
      depleted of a specific subset for the first 10 days of their lives by using
      either anti-CD4 or anti-CD8 monoclonal antibodies in vivo. Disease development in
      these mice was then monitored. Depletion of CD4+ T cells significantly attenuated
      the ts1-induced syndrome: virus replication was decreased, disease latency was
      extended, and death was prevented in 60% of the mice. Similar treatment with anti
      CD8 antibody had almost no effect on disease progression. However, when depletion
      was begun 2 weeks after neonatal ts1 inoculation, CD4+ T cell depletion did not
      affect disease development. ts1 infected CD4+ and CD8+ T lymphocytes equally well
      in vivo, as shown by flow cytometric analysis, but virus replication was
      restricted primarily to the CD4+ subset of T cells, as found by in vitro assay.
      Hence, CD4+ T lymphocytes play an important role in the development of ts1
      induced paralysis and immunodeficiency. The mechanism of this CD4+ T-cell
      mediated disease production by ts1 is not clear; however, increased replication
      of ts1 in the CD4+ T cells, especially in the early stages of the disease, seems
      to play a crucial role.

PMID- 1348545
TI  - Specific lysis of targets expressing varicella-zoster virus gpI or gpIV by CD4+
      human T-cell clones.
AB  - Varicella-zoster virus (VZV)-specific CD4-positive T cells are known to lyse
      targets expressing VZV antigen, but little is known of the glycoprotein
      specificity or phenotype of these cells. To test the ability of T cells to
      distinguish between gpI and gpIV (which share an antibody-defined epitope), we
      prepared clones from blood from four healthy individuals by limiting dilution.
      Among 68 T-cell clones from four donors which were VZV specific in tests of
      proliferation, 30 lysed autologous Epstein-Barr virus-transformed lymphoblasts
      which had been superinfected with a recombinant vaccinia virus which included the
      whole VZV gpI sequence. These clones were characterized as major
      histocompatibility complex class II restricted by inhibition of their
      cytotoxicity with HLA-DR and CD4 monoclonal antibodies. Twenty-one clones lysed
      targets expressing gpIV. Fifteen of these clones lysed targets expressing gpI and
      gpIV. Four clones with gpI-gpIV specificity were examined in detail, and their
      dual specificity was confirmed by cold target inhibition. These four clones
      failed to kill target cells infected with a mutant gpIV recombinant vaccinia
      virus from which amino acid residues 212 to 354 had been deleted. This region
      includes one of the two gpIV decapeptides which have 50% homology with amino
      acids 111 to 121 of gpI. Our data confirm that T-cell-receptor-associated
      structures are required for specific lysis of VZV targets and indicate that (i)
      gpI-specific CD4 cytotoxic T cells outnumber gpIV-specific T cells in blood and
      (ii) 50% of gpI-specific T-cell clones also lyse gpIV-expressing targets.

PMID- 1348547
TI  - Establishment and functional characterization of human herpesvirus 6-specific
      CD4+ human T-cell clones.
AB  - In order to clarify the protective immune responses against a newly identified
      herpesvirus, human herpesvirus 6 (HHV-6), we established HHV-6-specific human T
      cell clones and examined their functional properties. Five CD3+CD4+CD8- T-cell
      clones, which proliferated in response to stimulation with two different strains
      of HHV-6 in the presence of autologous antigen-presenting cells but not with
      herpes simplex virus type 1 or human cytomegalovirus, were established from
      peripheral blood lymphocytes of a healthy individual. The proliferative response
      of all T-cell clones to HHV-6 antigen was inhibited by addition of anti-HLA-DR
      monoclonal antibody, indicating that these clones were human leukocyte antigen
      (HLA) class II DR restricted. Of the five clones, two lysed HHV-6-infected
      autologous lymphoblasts, but not HHV-6-infected allogeneic cells or natural
      killer-sensitive K562 cells (group 1); one showed cytotoxicity against HHV-6
      infected autologous lymphoblasts as well as HHV-6-infected allogeneic cells and
      K562 cells (group 2); and the remaining two showed no cytotoxic activity (group
      3). The cytotoxic activity of group 1 was inhibited by addition of anti-HLA-DR
      monoclonal antibody to the culture, whereas this monoclonal antibody had no
      effect on the cytotoxicity of group 2 and did not induce the cytotoxicity of
      group 3. Perforin, which is one of the mediators of cytotoxicity, was abundantly
      expressed in group 1 and 2 clones. Moreover, all groups of clones produced gamma
      interferon after culture with antigen-presenting cells followed by HHV-6 antigen
      stimulation. These results suggest that HHV-6-specific CD4+ T cells have
      heterogeneous functions.

PMID- 1348546
TI  - Ovine lentivirus is macrophagetropic and does not replicate productively in T
      lymphocytes.
AB  - The lentiviruses of sheep, goats, and horses cause chronic multiorgan disease in
      which macrophages are highly permissive for viral replication. Monocytes, which
      mature into macrophages, are thought to be latently infected with lentivirus, but
      the extent to which other leukocytes are infected is unknown. Dendritic cells
      have not been studied separately from monocytes and T-cell subsets have not been
      examined in previous attempts to identify infected cells in peripheral blood
      mononuclear cells (PBMC). We found no evidence of T-cell tropism using an animal
      passaged, pathogenic ovine lentivirus. Phytohemagglutinin-stimulated infectious
      PBMC produced 20-fold less virus than differentiated macrophages, and
      cocultivation of infectious PBMC with fresh, uninfected phytohemagglutinin blasts
      did not facilitate virus replication. Furthermore, central lymph cells, the best
      in vivo source of purified lymphocytes, lacked virus and did not yield virus upon
      in vitro cultivation. In contrast, cultivated blood-derived macrophages were
      highly permissive for viral replication. To identify the latently infected PBMC,
      PBMC from infected sheep were selectively depleted of monocytes and B cells by
      passage over nylon wool and then of nonadherent cells bearing CD4, CD8, T19,
      gamma delta T-cell receptor, CD45RA, or major histocompatibility complex class II
      antigens by panning. Removal of adherent monocytes and B cells or of adherent
      cells and the three major T-cell subsets (CD4+, CD8+, T19+) did not decrease the
      infectivity of PBMC. The richest sources of infected cells in fresh PBMC were
      CD45RA+ and major histocompatibility complex class II+ nonadherent cells, which
      are three characteristics of dendritic cells. Thus, the dendritic cell, and not
      the monocyte or the CD4+ cell, is probably the predominant infected cell type in
      blood.

PMID- 1348549
TI  - [Autonomic nervous function and plasma catecholamine levels of perioperative
      patients treated with antipsychotic drugs].
AB  - The RR intervals on ECG and the coefficient of variation of R-R interval (CV) and
      perioperative plasma catecholamine levels were measured in patients receiving
      long-term administration of antipsychotic drugs. CV was significantly reduced (P
      less than 0.05) in patients on antipsychotic drugs. Preoperative plasma
      catecholamine levels increased significantly and elevation of plasma
      catecholamine levels on the first postoperative day was less than that of the
      control group. These findings suggest that the patients on antipsychotic drugs
      have disturbed autonomic nervous function. Therefore, a careful perioperative
      care is mandatory.

PMID- 1348548
TI  - Human herpesvirus 7 is a constitutive inhabitant of adult human saliva.
AB  - We report the frequent isolation of human herpesvirus 7 from the saliva of
      healthy adults. Virus isolates recovered from different individuals exhibited
      minimal restriction enzyme polymorphism, which was mostly confined to
      heterogeneous (het) sequences in the genome. DNAs of isolates recovered from the
      same individual over a period of several months showed the same characteristic
      het fragments, indicating the stability of the het sequences upon virus
      replication and shedding in vivo. In contrast to the results of previous reports,
      human herpesvirus 6, the causative agent of roseola infantum, could not be
      isolated from the saliva specimens, raising questions regarding oral transmission
      of human herpesvirus 6 and human herpesvirus 7 to young children.

PMID- 1348551
TI  - [Midwifery and research].

PMID- 1348550
TI  - [Evaluation of the timing principle with vecuronium].
AB  - We evaluated the usefulness of the timing principle with vecuronium in 60
      patients who underwent elective surgery, and divided into two groups according to
      the dose of vecuronium (0.15 and 0.2 mg.kg-1). First, we studied the interval
      between vecuronium and thiopental administration in 40 patients. The time after
      vecuronium administration to onset of clinical muscle weakness was 57.6 +/- 7.8
      sec in 0.15 mg.kg-1, and 42.2 +/- 2.2 sec in 0.2 mg.kg-1 group. Then, we made and
      examined the protocol of the timing principle for the rapid tracheal intubation.
      Induction of anesthesia with 4-5 mg.kg-1 thiopental was done 40 sec after 0.15
      mg.kg-1 in 10 patients, and 30 sec after 0.2 mg.kg-1 vecuronium administration in
      10 patients. Intubating conditions were almost excellent 70 sec after thiopental
      administration. In our study, there were no patients who experienced discomfort
      during induction. We conclude that the timing principle with vecuronium is useful
      for rapid-sequence tracheal intubation.

PMID- 1348553
TI  - [Abdominal injuries in polytraumatised patients].
AB  - Authors have observed in 1978-1984 in 87 of 214 polytrauma cases injuries of the
      abdominal organs. The data concerning children in whom the high ratio of injuries
      of the abdominal organs and the low mortality are conspicuous are shown
      separately. The necessity of urgent diagnosis to which especially the abdominal
      irrigation has given great help is stressed. After a review of the literature and
      a control of their own material the problem is considered as actual, as in
      polytraumas the abdominal injuries are frequent, the valuation of the abdomen in
      the patient, generally in shock or unconscious is problematic, the many times
      simultaneous therapy of the abdominal and joined injuries is difficult, the
      mortality high.

PMID- 1348552
TI  - [Early synovectomy in the treatment of juvenile rheumatoid arthritis].
AB  - Authors report on the results of 15 synovectomies of the knee for iligoarticular
      juvenile rheumatoid arthritis. The operation was performed in every case in the
      early stage before the development of the radiological destruction. Excellent and
      good results were obtained in 11 cases; in 4 cases the operation was
      unsuccessful. It is stated that there is good chance to prevent destruction of
      the knee with juvenile rheumatic arthritis with an early synocvectomy. The
      operation is suggested after 6 years of age. The key of the good result is the
      early intensive mobilization of the joint.

PMID- 1348554
TI  - [Results of sonographic hip examination of infants in a risk group].
AB  - During sonographic examination of 770 newborns and infants the diagnostic value
      and the possibility of valuation of singular risk factors were investigated.
      According our data an acetabular dysplasia, requiring treatment can be found most
      frequently in the background of a limitation of abduction motion. Pathologic
      alterations may be found less frequently in groups with familiar anamnesis and
      with breech presentation. It could be stated that the aspecific click is a
      clinical symptom of significance and cannot be neglected whereas we could not
      prove connections between asymmetry of the folds and the sonographic data. Our
      results prove that the anamnesis and the clinical symptoms alone do not make a
      perfect recognition of the dysplasia possible; in consequence it is suggested
      that sonography should be used as a screening.

PMID- 1348555
TI  - [Ultrasonic examination of soft tissue injuries in the shoulder region].
AB  - Authors call attention with the demonstration of pictures of a few cases of their
      own to the significance of the ultrasound examination in cases of shoulder
      injuries. They stress that beside the demonstration of rotator cuff injuries the
      examination of the surrounding muscles and the labrum glenoidale should not be
      forgotten either. The modernization of the ultrasound devices, the improvement of
      the methods of examination and the obtaining of the necessary practice ensure a
      more and more important place to echography in the diagnosis of traumas of the
      motion organs.

PMID- 1348556
TI  - [Treatment of idiopathic femur head necrosis by implantation of a preserved bone
      graft. Critical evaluation of the method].
AB  - Author reports on the result of treatment in 22 patients with idiopathic femoral
      head necrosis. Altogether 25 hips were treated with insertion of conserved bone
      graft. Improvement occurred in only about 1/4 of the operated hips, the other
      hips deteriorated both clinically and radiologically. The author thinks,
      reviewing the literature, that the cause of the partly failure was the inadequate
      selection of patients and the insufficiency of the method. The possibilities of
      further progression are outlined.

PMID- 1348557
TI  - [Management of tibial fractures with Ender nailing].
AB  - Authors have performed in 1984-1986 46 Ender nailings based on definite
      indications as treatment of lower leg fractures in the Department of
      Traumatology, Arpad Hospital, Ujpest. In their clinical study they stress the
      criteria of the choice of this method, underline the advantages and disadvantages
      of the stabilization with elastic nails. This treatment used especially for
      fractures of the distal third lightens the care, the mobilization, shortens the
      stay in the hospital, diminishes the number of the septic complications. In many
      cases authors recommend it as a good alternative method, based on own experiences
      and results, to surgeons forced to accept a compromise.

PMID- 1348558
TI  - [Emergency treatment of severe burns in daily practice].
AB  - The paper examines the initial treatment of the severely burned patient to be
      transferred. It is stated that the aspirations for a uniform expert treatment
      have not yet brought a complete success. The suggestions concerning this problem,
      described in the Methodological Letter "Treatment of Thermic Injuries" issued by
      the Nat. Institute of Traumatology are discussed and repeated.

PMID- 1348559
TI  - [Bicycle accidents].
AB  - Authors analyse the 1684 bicycle accidents, observed in the county Vas in one
      year, compared with the international data. It is underlined that no sufficient
      attention is given to the bicycle accidents, reaching 6 per cents of all traumas,
      and the increase of which can be still expected, and to the prophylaxis of these
      accidents. Especially endangered were found the little children transported on
      bicycles, those aged 11-14 years and the drunken drivers. Prophylactic measures
      are suggested.

PMID- 1348560
TI  - [Management of lower leg fractures by external fixators and thermoplastic braces.
      Preliminary report].
AB  - Authors describe their new combined method for treatment of lower leg fractures.
      To this a new type fixator was developed which makes dynamization also possible.
      The other novelty in this country is the use of functional external fixing brace.
      In all of the 38 patients they had succeeded to obtain healing. No complication
      was found until now.

PMID- 1348561
TI  - [Chondromatosis of the hip joint].
AB  - The case of a 42 years old man is described who had complaints in his left hip
      since 9 years for synovial chondromatosis. During the operation 38 cartilaginous
      free bi dies were removed and at the same time synovectomy was also performed.
      The chondroma not observed and not removed at the exposure was spontaneously
      resorbed during the follow-up time. Authors think the case interesting because
      during the last 30 years no similar description was found in the Hungarian
      literature.

PMID- 1348562
TI  - [Possibilities of surgical management of fractures of the scapular corpus].
AB  - Authors report on the possibilities of the operative treatment of the corpus
      scapulae. In chosen cases--young patients, isolated occurrence, great dislocation
      -they have performed the plate osteosynthesis of the corpus fractures. The
      frequency of the occurrence, the classification of fractures, the possibilities
      of the operative technique, the indication of the operations, the postoperative
      therapy are mentioned and their cases are described.

PMID- 1348563
TI  - [The role of Gardner's classification in the detection of dislocation in femoral
      neck fractures].
AB  - As the literary data are contradictory, authors examined in 489 operated femoral
      neck fractures the significance of Garden's classification. Based on their
      material it was found that this classification gives help in the judgement of the
      single fractures and in the choice of the adequate treatment. For a more exact
      assessment however they think the consideration of the lateral Roentgenograms
      also necessary.

PMID- 1348564
TI  - [Bone transplantation methods].
AB  - Author sums on the basis of the literature of this country and of the
      international literature the more frequently used methods of bone substitution,
      their mechanical and biological characteristics. On the basis of the practice of
      their institute and of the international publications it can be stated that
      beside the usual transplantation of preserved bone the always increasing clinical
      claim makes the introduction and the knowledge of other methods also necessary.
      The advantages and disadvantages of the bone grafts of different types are
      detailed. It is stated that none of the implantates of different characteristics
      fulfils perfectly the ideal mechanical and biological requirements. To obtain the
      possibly best result it is recommended to choose, and on individual indication,
      the bone substitution method that will fulfil in the given case the requirements
      desired.

PMID- 1348565
TI  - Effect of sialectomy on the superior cervical ganglion sympathetic neurons in
      young adult and aged mice.
AB  - The dependence of superior cervical ganglion (SCG) adrenergic neurons on their
      target organ submandibular salivary gland containing high concentrations of nerve
      growth factor was studied in adult and aged male mice. The submandibular salivary
      glands were removed (sialectomy) either uni- or bilaterally, and the SCG were
      studied by fluorescence microscopy and histochemically. Catecholamine
      fluorescence and tyrosine hydroxylase immunoreactivity decreased after
      sialectomy, suggesting reduced noradrenaline production. Neuronal density was
      lower in the aged controls than in the young controls. In both age groups,
      sialectomy reduced the density of catecholamine-producing neurons. In the mouse
      SCG, there was remarkable heterogeneity in the size of neuronal somata. In aged
      control mice there was a greater number of large-size neurons than in young adult
      control mice. Six weeks postoperatively, no large catecholamine-producing neurons
      could be observed in the ganglia. Yellow autofluorescent lipopigments accumulated
      with age in the adrenergic neurons. Sialectomy increased the accumulation of
      lipopigments in both young and aged neurons. Sialectomy resulted in (a) reduced
      catecholamine fluorescence, (b) reduced tyrosine hydroxylase immunoreactivity,
      (c) reduced number of catecholamine neurons, (d) increased autofluorescent
      lipopigment. Ageing resulted in (a) reduced number of neurons, (b) increased
      ratio of large to small neurons, (c) increased autofluorescent lipopigment.
      Alterations after sialectomy were more detrimental in the aged ganglia than in
      the young adult ganglia. The discontinuation of the retrograde supply of nerve
      growth factor may contribute to these alterations.

PMID- 1348566
TI  - Biogenic amines in the guinea pig endocrine pancreas.
AB  - Pancreata of guinea-pigs were investigated for the presence and cellular
      distribution of biogenic amines. Out of the established endocrine cell types only
      insulin (B-) cells contained immunoreactivity for serotonin and noradrenaline.
      However, the B-cells' content of both amines was quite variable. Serotonin was
      also confined to enterochromaffin (EC-) cells. No immunoreactivity for dopamine
      or histamine was present in any islet cell. Treatment of guinea-pigs with Ro-4
      4602 led to a marked decrease of serotonin and noradrenaline in pancreatic
      endocrine cells. The present findings suggest that serotonin and noradrenaline
      are involved in the function of the endocrine pancreas, particularly of islet B
      cells.

PMID- 1348567
TI  - Detection of genes coding for listeriolysin and Listeria monocytogenes antigen A
      (ImaA) in Listeria spp. by the polymerase chain reaction.
AB  - Two pairs of synthetic oligonucleotide primers were used in a polymerase chain
      reaction (PCR) protocol to detect targeted sequences in genes coding for
      listeriolysin O and Listeria monocytogenes antigen A (ImaA). Strains of Listeria
      spp. used in this study were isolated from clinical specimens, contaminated
      foods, and environmental sources. Primers were targeted to internal regions of
      the genes coding for listeriolysin (hlyA) and Listeria antigen (ImaA) and
      amplification fragments were detected after the PCR by agarose gel
      electrophoresis. PCR was performed using nucleic acids extracted from a
      collection of 74 strains of Listeria spp. including 18 reference strains, 41 L.
      monocytogenes, nine L. innocua, five L. seeligeri and one L. ivanovii,
      encompassing representative sources, serovars, and enzyme electrophoretic types.
      Although the listeriolysin gene was found exclusively in L. monocytogenes, some
      strains of serovar 4c were negative. Simultaneous presence of both genes was
      restricted to L. monocytogenes strains of serovars 1/2, 3, and 4. The ImaA gene
      was identified in five of 10 L. innocua strains and one L. ivanovii isolated from
      pork. Strains of L. seeligeri, L. welshimeri, and L. grayi were negative for both
      genes. The detection limits in the PCR were found to be 10 pg of nucleic acids
      for the hlyA gene and 1 pg for the ImaA gene.

PMID- 1348568
TI  - Drug-resistant TB may bring epidemic.

PMID- 1348569
TI  - Spongiform encephalopathies. PrP and the scrapie agent.

PMID- 1348570
TI  - Amphotericin B treatment dissociates in vivo replication of the scrapie agent
      from PrP accumulation.
AB  - Scrapie and related animal and human disorders are neurodegenerative diseases
      characterized by the formation of a modified, partly proteinase-resistant protein
      (PrP) of the host, which tends to aggregate as amyloid fibrils and accumulate in
      the brain of infected individuals. There is a general consensus that the
      pathological form of PrP (PrPSc) is essential for the clinical appearance of the
      disease, but whether it is part of the scrapie agent or a by-product of viral
      infection is still controversial. Here we report that treatment of scrapie
      infected hamsters with amphotericin B delays the accumulation in the brain of the
      proteinase-resistant portion of PrPSc by about 30 days without affecting scrapie
      replication. The consequence is that hamsters treated with amphotericin B
      developed clinical signs of disease later than infected controls. We argue that
      the proteinase-resistant portion of PrPSc is necessary for the development of the
      disease but that it is unlikely to be essential for scrapie replication.

PMID- 1348572
TI  - Bipotential precursors of B cells and macrophages in murine fetal liver.
AB  - LYMPHOCYTES (B and T cells) derive continuously from the same multipotential stem
      cells that produce myeloid cells, including erythrocytes, granulocytes and
      macrophages. Tri- and bipotential myeloid intermediates between the
      multipotential stem cells and later unipotential cells have been identified using
      clonal methods in culture. Although similar methods have detected committed pre-B
      cells in mouse fetal liver, earlier progenitors with additional non-B lineage
      options have not been demonstrated in normal tissues. We report the
      characterization and purification of fetal liver cells that generate clones
      containing both macrophages and B cells, identified biochemically and
      morphologically. The common origin of the two cell types was shown by culture of
      single precursor cells. Their dual potential and unrearranged immunoglobulin loci
      place the precursors before exclusive B-lineage commitment in the haematopoietic
      hierarchy. The availability of such cells in purified form will allow direct
      study of lineage choice in cells having both lymphoid and non-lymphoid options.

PMID- 1348571
TI  - Homeodomain-independent activity of the fushi tarazu polypeptide in Drosophila
      embryos.
AB  - The Drosophila segmentation gene fushi tarazu (ftz) encodes a homeodomain
      containing protein, ftz, that can act as a DNA-binding activator of
      transcription. In the developing embryo, ftz is expressed in seven stripes which
      correspond to the even-numbered parasegments. These parasegments are missing in
      ftz- embryos. When ftz is expressed throughout blastoderm embryos under the
      control of a heat-shock promoter, the odd-numbered parasegments are lost. This
      'anti-ftz' phenotype has been attributed to autoactivation of the endogenous ftz
      gene by the ectopically expressed protein. Here we show that the same phenotype
      is induced by ectopic expression of a ftz polypeptide containing a deletion in
      the homeodomain. Thus, ftz can alter gene expression without binding directly to
      DNA.

PMID- 1348573
TI  - PD meeting illustrates how search for adequacy continues.

PMID- 1348575
TI  - [Backpain Satellite Symposium, 77th meeting of the German Society of Orthopedics
      and Traumatology. Hamburg, 23 September 1991].

PMID- 1348574
TI  - [Parkinsonism following addition of fluoxetine to treatment with neuroleptics or
      carbamazepine].

PMID- 1348576
TI  - The jejunal secretory response to Escherichia coli heat-stable enterotoxin is
      prolonged in malnourished rats.
AB  - Undernutrition in human infants is associated with more prolonged episodes of
      diarrheal disease. Therefore, we tested the hypothesis that malnutrition prolongs
      the duration of Escherichia coli heat-stable enterotoxin-induced rat jejunal
      secretion. At weaning, rats were separated into two groups: malnourished rats
      were fed 50% of the previous day's intake of the fully fed control group. After
      approximately 2 wk of pair feeding, when malnourished rats weighed less than or
      equal to 60% of the full fed control group, we measured the secretory response to
      heat-stable enterotoxin in ligated jejunal loops. Toxin-induced secretion was
      equal in both groups until 30 min incubation time, after which net secretion
      continued to increase in the malnourished group but decreased in the fully fed
      group. Jejunal brush border membranes prepared from malnourished and fully fed
      rats demonstrated similar heat-stable enterotoxin receptor density, avidity of
      binding and guanyl cyclase activation. In both groups, radiolabeled toxin
      injected into in situ jejunal loops was converted into an altered radioligand
      unable to bind to brush border membranes. However, in malnourished rats, there
      was both increased appearance of two additional radioligands that still retained
      their ability to bind to brush border membranes and persistence of biologically
      active unlabeled toxin as measured in the suckling mouse bioassay. Our studies
      demonstrate that reduced or delayed inactivation of heat-stable enterotoxin, with
      continued presence of active toxin species, may contribute to prolonged secretion
      in the jejunum of malnourished rats.

PMID- 1348577
TI  - Non-phenotypic selection of N-methyl-N-nitrosourea-induced mutations in human
      cells.
AB  - The distribution of mutations in a particular gene as detected by a selective
      mutation assay could be affected by the structural properties of the target
      protein. To investigate this, we have analysed N-methyl-N-nitrosourea (MNU)
      induced mutations in two restriction recognition sequences of a target gene for
      mutation analysis and compared these data with what previously observed in a
      phenotypic mutation assay. DNA base changes in the Ncil and EcoRV sites of the
      gpt gene maintained in human cells by a shuttle vector system were measured by
      restriction fragment length polymorphism/polymerase chain reaction (RFLP/PCR)
      technique. After MNU-treatment of human cells, mutations were detected in the
      Ncil recognition sequence but not in the EcoRV site. DNA sequencing analysis
      revealed that all Ncil-resistant mutations were GC to AT transitions located over
      four bases of the Ncil recognition sequence. Only one of these mutations
      drastically affected the functionality of the GPT protein. The Ncil-resistant
      mutations were randomly distributed in both DNA strands of the gpt gene and were
      preferentially targeted at guanine residues flanked 5' by a guanine. Our results
      indicate that the structure of the GPT protein is the main contributor to the
      strand-specificity of MNU-induced mutations previously reported by using a
      phenotypic mutation assay. The potential use of the RFLP/PCR technique as a
      general tool for mutation detection is also discussed.

PMID- 1348578
TI  - A tight linkage cluster, with two new RFLPs (D8S96 and D8S108), in the interval
      8cen-q13.

PMID- 1348579
TI  - RFLP for BgI II at the human neurofilament medium chain (NEF3) gene locus.

PMID- 1348580
TI  - An MboI polymorphism at codon 192 of the human tyrosinase gene is present in
      Asians and Afrocaribbeans.

PMID- 1348581
TI  - Leukocyte adhesion deficiency: clinical and postmortem observations.
AB  - The clinical and autopsy findings in a patient with the severe form of leukocyte
      adhesion deficiency are presented. An 18-month-old Hispanic female had a history
      of delayed umbilical cord separation, recurrent necrotizing skin lesions, and
      gingivitis. Her neutrophils were found to lack detectable CD11/CD18 adhesion
      glycoproteins and were deficient in adhesion-dependent functions. She succumbed
      to necrotizing enterocolitis, peritonitis, and pneumonia following sudden
      cardiorespiratory collapse. Postmortem examination revealed multiple regions of
      mucosal ulceration and bacterial and fungal overgrowth with complete lack of an
      acute inflammatory response. Impaired neutrophil emigration from blood vessels
      into injured tissue appears to have been the basis of this patient's disease.
      Some of the many foci of bronchopneumonia, in contrast, contained numerous
      neutrophils. Lymphoid tissue, including the thymus, was severely depleted of
      lymphocytes. These findings support the concepts that neutrophils can emigrate in
      response to certain stimuli via CD18-independent mechanisms and that severe
      deficiency of CD18 is associated with compromised function of lymphocytes in
      vivo.

PMID- 1348582
TI  - Histiocytes in familial and infection-induced/idiopathic hemophagocytic syndromes
      may exhibit phenotypic differences.
AB  - Familial hemophagocytic syndrome (FHS) and infection-associated hemophagocytic
      syndrome (IAHS) usually present with fever, pancytopenia, hepatosplenomegaly,
      signs of hepatic dysfunction, bleeding diathesis, and neurological
      manifestations. FHS is almost uniformly fatal, and IAHS is associated with high
      mortality. The only distinguishing characteristics are lack of family history and
      association with infection in the latter. Despite this, sporadic cases of FHS and
      culture-negative examples of IAHS (idiopathic HS) can be difficult to distinguish
      and the distinction may have important implications for treatment and family
      planning. We evaluated the immunophenotype of the macrophages (M phi s) in frozen
      tissue sections from three cases of hemophagocytic syndrome using a very large
      panel of monocyte/M phi-associated monoclonal antibodies and an immunoperoxidase
      technique. The clinical and laboratory features suggested that two were examples
      of FHS (one with strong family history) and that the third was IAHS/idiopathic
      HS. The results supported the clinical impressions by showing that the antigenic
      phenotypes of the FHS cases were nearly identical and different from that of the
      case of presumed IAHS/idiopathic HS. Specifically, M phi s from the FHS cases
      expressed complement receptors, 1, 2, and 3 (CD35, CD21, and CD11b,
      respectively), the monocyte antigen CD36, and the "activation" antigens CD25 (IL2
      R) and CD30 (Ki-1), while those from the IAHS/idiopathic case did not. These
      studies also demonstrated that the M phi s in these cases exhibited some
      phenotypic differences from those in control tissues, that is, expression of the
      pan-M phi antigen CD14, the M phi subset antigen identified by antibody G16/1,
      complement receptors, certain monocyte antigens, and M phi "activation"
      antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348583
TI  - Effect of typical antipsychotic medications and clozapine on smooth pursuit
      performance in patients with schizophrenia.
AB  - The effect of typical neuroleptic drugs or clozapine on smooth pursuit eye
      movements was tested in 13 patients with schizophrenia or schizoaffective
      disorder with a repeated measures design. Nineteen normal control subjects were
      also studied. Compared with controls, patients in the unmedicated state had low
      smooth pursuit gain, had a higher rate of corrective catch-up saccades, and
      tended to spend less time engaged in the tracking task. The patients did not
      significantly differ from controls on catch-up saccade amplitude, square wave
      jerk rate, or anticipatory saccade rate. Medication with clozapine, but not
      typical neuroleptics, was associated with an increase in median catch-up saccade
      amplitude. Number of days on clozapine and clozapine dose both correlated
      significantly with a worsening of oculomotor performance. No effect of medication
      with typical neuroleptics was found, although there was some evidence suggesting
      that such an affect may occur after more prolonged treatment.

PMID- 1348584
TI  - Treatment of extrapyramidal side effects with terguride.
AB  - Terguride, a partial dopamine agonist, was administered in a 4-week open clinical
      trial to 17 schizophrenic patients suffering from extrapyramidal side effects of
      neuroleptic treatment. The neuroleptic dosage was kept constant. The mean final
      daily dose of terguride reached 3.4 mg (SD = 2.0). Fourteen patients completed
      the trial. Total scores on the Rating Scale for Extrapyramidal Side Effects and
      the Brief Psychiatric Rating Scale showed a significant improvement of 69% and
      40%, respectively. There was also a significant improvement in all BPRS factor
      scores.

PMID- 1348585
TI  - Enzymuria and tubular proteinuria in diabetic rats: a 12-week follow-up study.
AB  - Various biochemical parameters of renal tubular function were examined for a
      period of up to 12 weeks in rats rendered diabetic by an i.v. injection of
      streptozotocin. Except for a statistically significant decrease in the urinary
      excretion of gamma-glutamyl-transpeptidase to 64% of control values, the urinary
      excretion of beta-N-acetyl-D-glucosaminidase, beta-galactosidase, alanine
      aminopeptidase, and lactate dehydrogenase significantly increases in diabetic
      rats to between 154% and 712% of control values. This increased enzymuria is not
      correlated to the marked polyuria induced by diabetes (r between 0.14 and 0.35,
      not significant). Enzymuria is also accompanied by a 10-fold increase in the
      urinary excretion of the low molecular weight protein beta 2-microglobulin while
      the excretion of albumin is not significantly modified, indicating impairment of
      tubular reabsorption in diabetic animals. Clearance studies reveal that the
      clearance of both beta 2-microglobulin and infused egg-white lysozyme are also
      increased. Finally the histopathologic examination of paraffin sections of the
      kidney show hydropic degenerescence and pycnosis of the tubular cells. It is
      concluded that early-stage diabetes results in tubular impairment and that the
      streptozotocin-rat model appears well suited to the study of these early signs of
      renal dysfunction.

PMID- 1348586
TI  - Polymorphism of the tumor necrosis factor region in relation to disease: an
      overview.
AB  - HLA antigens have been shown to be associated with several immunoinflammatory
      diseases. The mechanisms by which these antigens confer susceptibility to disease
      continue to be of major interest. Rapid progress has been made in the elucidation
      of the structure and function of class I and II MHC molecules, and several genes
      located within the HLA complex have been identified which are potentially
      involved in immunologic processes. Because of the HLA localization of the TNF
      alpha and -beta genes and the biologic activities of the gene products, recent
      investigation has focused on a possible role of polymorphic TNF genes in the
      pathogenesis of HLA-associated diseases. Allelic variations have only been
      detected in the TNF-beta gene. No evidence has been found so far that a
      particular TNF-beta allele contributes significantly in the susceptibility to the
      diseases studied. Although it has been postulated that the TNF beta*2 allele
      contributes to susceptibility to IDDM in HLA-DR3, 4 heterozygous individuals, a
      larger group of HLA-typed patients and controls is needed to provide more
      conclusive evidence for this hypothesis. The increasing number of genes of
      unknown function encoded by the class III region leaves the possibility that the
      observed HLA associations in some diseases may be related to the presence of
      these genes. In AS, the lack of association with the TNF-beta alleles furthermore
      supports the function of the HLA-B27 molecule in the disease and underlines the
      improbability that HLA-B27 is merely a marker for a closely linked susceptibility
      gene.

PMID- 1348587
TI  - [Treatment of acute pain in a general hospital: opinions of physicians and
      nurses].
AB  - A survey was carried amongst physicians and nurses of a general hospital, in
      order to know their opinion about acute pain treatment. Out of 106 physicians and
      153 nurses questioned, 72 and 105 respectively answered the questionnaire. Two
      thirds of them though that analgesic treatment was currently good, although, it
      could be improved if they increased their knowledge about it. Twenty nine per
      cent of physicians thought that their patients were receiving lower doses than
      what they had prescribed and that this fact could be responsible for the
      treatment failure. Those questioned believed that approximately 30% of patients
      treated with opium derivatives for over a week could develop addiction problems.
      Our study confirmed the existence of inadequate attitudes towards the need for
      analgesics in patients with acute pain.

PMID- 1348588
TI  - Serum and tissue transglutaminase correlates with the severity of inflammation in
      induced colitis in the rat.
AB  - Simple rat models of acute and chronic colonic inflammation were used to study
      the behaviour in serum and mucosa of transglutaminase (TG), an enzyme recently
      found to be reduced in serum of patients with inflammatory bowel disease (IBD)
      and related to the activity index of the disease. In the first model the
      intraluminal administration of 400 mM lactic acid in the colon caused an acute
      inflammation resembling that of florid ulcerative colitis in humans. In the
      second, intraluminal administration of the hapten 2,4,6-trinitrobenzenesulphonic
      acid (TNB) (10 or 30 mg) in 0.25 ml of ethanol as a 'barrier breaker' produced a
      chronic inflammatory disease. The results showed a reduced TG activity in colon
      of rats in both acute and chronic induced colitis (447 +/- 75 versus 1344 +/- 59
      mU/g protein (p less than 0.001) and 484 +/- 59 versus 1204 +/- 75 mU/g protein
      (p less than 0.001)). This decreased activity was related to the severity of
      mucosal damage, which was dose-dependent. Moreover, in severe colitis the
      immunohistochemistry showed a TG location in repairing tissue. Serum TG activity
      was decreased after TNB administration (1.36 +/- 0.05 versus 3.44 +/- 0.20 mU/ml
      (p less than 0.001)) but not after lactic acid treatment (3.97 +/- 0.11 versus
      3.78 +/- 0.16 mU/ml). In summary, the reduction of TG activity in both tissue and
      serum when the damage is stabilized reflects the altered morphofunctional
      integrity of the colon and suggests that serum assay of this enzyme could be a
      simple marker of intestinal mucosal status in IBD.

PMID- 1348589
TI  - Flow-cytometric analysis of growth-regulatory peptides and their receptors in
      Barrett's oesophagus and oesophageal adenocarcinoma.
AB  - The conventional assessment of the premalignant potential of Barrett's oesophagus
      is unsatisfactory. However, it has recently been shown that abnormalities of
      growth-regulatory peptides and their receptors may be important in the
      pathogenesis of this condition. In an attempt to improve the diagnostic and
      prognostic criteria we have studied 21 consecutive patients with Barrett's
      oesophagus and 7 others with adenocarcinoma of the oesophagus. In each patient
      biopsy specimens were taken from the columnarlined oesophagus or the
      adenocarcinoma and from the gastric cardiac mucosa for routine histologic
      evaluation. Immediately adjacent specimens were taken from both the Barrett's
      mucosa or adenocarcinoma and from the gastric mucosa for flow-cytometric study.
      The latter samples were disaggregated and labelled with antibodies to epidermal
      growth factor (EGF), transforming growth factor alpha (TGF-alpha), and epidermal
      growth factor receptor (EGF-R). The flow cytometer selected cells labelled with
      each antibody and expressed them as a percentage of the total number of
      disaggregated cells (average, 5500 cells). Epidermal growth factor receptors were
      expressed in a greater number of cells from Barrett's mucosa, with the intestinal
      type or those with dysplasia, than in gastric cardiac mucosa (p less than 0.05).
      All seven adenocarcinoma had many more cells expressing EGF, TGF-alpha, and EGF-R
      than normal gastric mucosa (p less than 0.01). We conclude that flow-cytometric
      evaluation of EGF-R can help in the understanding of the pathogenesis of
      Barrett's oesophagus.

PMID- 1348590
TI  - [HIV-associated malignant lymphomas].
AB  - In a retrospective analysis of data from 35 cases with malignant lymphoma from a
      cohort of 2017 HIV-infected patients, the stage of HIV-disease, the CD4 counts at
      the time of diagnosis, and the use of antineoplastic agents or radiotherapy were
      correlated with outcome. 6 patients had Hodgkin's lymphoma (HL) and 29 non
      Hodgkin-lymphoma (NHL). 11 of these lymphomas were classified according to the
      international working formulation (IWF) as high grade (H, I and J, respectively)
      and 8 as intermediate grade (G). 10 could not be classified. 22 patients with NHL
      had stage IV disease according to the Ann Arbor classification, all of whom had
      manifestations at extranodular sites. 23 patients with NHL were treated with
      multiagent chemotherapy (18 with m-BACOD or CHOP, 5 patients with various other
      regimens) and four of them had additional radiotherapy. One patient received
      radiotherapy only. Two of 24 treated patients showed complete and five a partial
      response. Median survival of patients without treatment (all of them in poor
      general condition at the time of diagnosis) was 1.8 months and treated patients
      survived a median of 5 months. The pretreatment CD4 count was the most important
      predictor of survival. Patients with prior Aids-diagnosis showed a tendency
      towards shorter survival. The observed remission rate indicates that HL in HIV
      infected patients is better treatable than HIV-associated NHL. However, the
      overall outcome of HL in our patients was clearly less favorable compared to the
      course of HL usually seen in patients without HIV infection. The proportion of
      patients with HL among all patients with malignant lymphoma and HIV disease was
      unexpectedly larger in our cohort compared to others. Therefore, a possible
      association of HL and HIV infection, as addressed by several other authors, needs
      further clarification.

PMID- 1348591
TI  - Neuroleptics in alcohol withdrawal.

PMID- 1348592
TI  - Efflux of glutamate produced by short ischemia of varied severity in rat
      striatum.
AB  - BACKGROUND AND PURPOSE: Evidence has accumulated suggesting that ischemia-induced
      neuronal damage may be linked to an extracellular overflow of glutamate. The
      purpose of this study was to provide new information about the time course of the
      increase in extracellular glutamate concentration associated with moderate and
      severe ischemia, and its relationship with electrical changes including anoxic
      depolarization. METHODS: Changes in the extracellular concentration of glutamate
      were continuously monitored in the rat striatum by microdialysis. Ischemia was
      induced by four-vessel occlusion for 3 or 5 minutes, and in some cases its
      severity was increased with a neck tourniquet. The severity of ischemia was
      assessed by electroencephalogram and direct current potential recording to detect
      anoxic depolarization. RESULTS: In all experiments, the extracellular glutamate
      concentration began to increase shortly after the onset of ischemia and steadily
      rose throughout the ischemic period. Increases up to 35.0 mumol/l (2-3 mumol/l
      baseline; p less than 0.005) were observed when ischemia provoked the rapid
      occurrence of a large and sustained anoxic depolarization. Relatively smaller but
      still significant increases (6.9 mumol/l; p less than 0.005) were observed in
      penumbral conditions (electroencephalogram loss without anoxic depolarization).
      Glutamate began to be cleared immediately after reperfusion and 90% of released
      glutamate was cleared within 5 minutes, even when the preceding ischemia had been
      severe. CONCLUSIONS: We propose that the extracellular glutamate concentration
      may not reach critical levels during short episodes of penumbral ischemia, but
      this might happen with a longer ischemic period.

PMID- 1348593
TI  - Genomic analysis of Theileria sergenti stocks in Japan with DNA probes.
AB  - Restriction fragment length polymorphisms of Theileria sergenti DNA from 18
      different infections of cattle in 14 locations in Japan were analyzed by Southern
      blotting using T. sergenti genomic DNA fragments as probes. Probe pTs 2
      hybridized with four fragments in BamHI digested piroplasm DNA, at 8.0, 7.3, 6.0
      and 3.4 kb. Probe pTs 11-D1 hybridized with multiple fragments. With each probe,
      polymorphisms were observed among stocks from different locations. However, there
      was no correlation between the patterns of hybridization bands and the locations
      where parasites were collected. Analysis of the hybridization patterns of stocks
      obtained from individual cattle in the same grazing areas showed an almost
      identical pattern.

PMID- 1348595
TI  - Preliminary human trial of inactivated golden hamster kidney cell (GHKC) vaccine
      against haemorrhagic fever with renal syndrome (HFRS).
AB  - An inactivated golden hamster kidney cell culture (GHKC) vaccine against
      haemorrhagic fever with renal syndrome (HFRS) has been developed in recent years.
      A monovalent GHKC vaccine (lot 88-17) was prepared with L99 strain of the rat
      type hantavirus, adapted in suckling mouse brain, cultivated in GHKC, and
      inactivated with 0.025% formalin, and a preliminary trial of the vaccine was
      carried out in a small number of human volunteers with the approval of the
      Ministry of Public Health, PRC, in order to identify safety and antibody response
      of the vaccine. Three inoculations were made on days 0, 7 and 28 respectively, by
      the intramuscular route with 1 ml vaccine each time for every volunteer. No
      obvious side effect was observed in vaccinees within 3 days after each
      inoculation. All 12 vaccinees (10 received three inoculations, and two received
      two inoculations of the vaccine) showed positive seroconversion of IgG antibody
      (by IFAT and ELISA) and neutralizing antibody (by enzyme focus reduction
      neutralization test, EFRNT), and 10 of them were still seropositive 180 and 360
      days after the first inoculation. These results suggest that this vaccine would
      be safe for human use, and could effectively induce IgG and neutralizing antibody
      responses.

PMID- 1348594
TI  - Maintenance therapy: is there still a place for antireflux surgery?
AB  - Effective and safe maintenance medical therapy for uncomplicated reflux
      esophagitis is now feasible with omeprazole and it is likely that other
      H+K+ATPase blockers, and possibly very high dose H2 receptor antagonist regimens,
      will also be acceptable. In addition, many patients with ulceration, strictures,
      and Barrett's esophagus will respond to conservative medical therapy and a
      proportion of patients with erosive esophagitis may remain in remission with
      cisapride or with low dose H2 receptor antagonists, if disease is less severe.
      Thus, there is now a medical "gold standard" against which surgical therapy for
      uncomplicated esophagitis must be judged and it is essential that all future
      studies be conducted with clearly defined criteria for the assessment of the
      symptoms and endoscopic signs of esophagitis and its complications. As ever, the
      patient's wishes are paramount, but he or she must be allowed to select his or
      her therapy on the basis of a balanced and fully informed assessment of the long
      term and short-term risks of all therapeutic modalities. The burdensome prospect
      of lifelong tablet ingestion and its potential dangers must be weighed against
      the alternative, in up to 30% of cases, that surgery may produce dysphagia, gas
      bloat, or dumping with no guarantee of a long-term cure.

PMID- 1348596
TI  - On the application of mathematical models of schistosome transmission dynamics.
      II. Control.
AB  - Mathematical models have considerable potential as aids to the design of
      schistosome control programmes. This is because of the complex nature of the
      schistosome transmission cycle and the variety of control measures available,
      which make the comparative effectiveness of different control options extremely
      difficult to predict. This review aims to demonstrate how control can be
      incorporated in models of schistosome transmission dynamics, and to make explicit
      the assumptions and limitations of the models and their relationships with field
      data. A basic model is described which considers changes in the mean number of
      schistosomes per person. The criteria for the eradication of endemic infection
      and the potential for reducing levels of infection are discussed. The treatment
      of various control measures within this framework is reviewed. These include:
      chemotherapy (mass, selective and targeted), molluscicide application (blanket
      and focal) and other snail control measures, larval stage control, improved water
      supplies and sanitation, and health education. The incorporation of economic
      variables is also discussed. The choice between different control options depends
      on the relationships between schistosome epidemiology and the costs and effects
      of control. The evaluation of cost-effectiveness is a dynamic problem, and the
      outcome will depend on local conditions and constraints. Very general
      recommendations for the design of schistosome control programmes are unlikely to
      prove useful.

PMID- 1348597
TI  - Identification of a surface metalloproteinase on 13 species of Leishmania
      isolated from humans, Crithidia fasciculata, and Herpetomonas samuelpessoai.
AB  - Promastigotes of thirteen species of Leishmania isolated from human patients, as
      well as L. enriettii, Crithidia fasciculata and Herpetomonas samuelpessoai, were
      examined for the expression of an amphiphilic, surface-oriented metalloproteinase
      by surface radioiodination of living cells, fractionation by Triton X-114
      extraction and phase separation, and zymogram analysis by fibrinogen-SDS-PAGE. In
      all species of Leishmania, and the two monoxenous trypanosomatid parasites of
      insects, an ectoproteinase similar to the Promastigote Surface Protease, or PSP,
      was observed. In contrast, neither Phytomonas sp. nor 'Leishmania tarentolae'
      express a detectable surface metalloproteinase. The presence of the functionally
      conserved metalloproteinase at the surface of Crithidia and Herpetomonas suggest
      the enzyme may not be involved in the infection of the mammalian host by
      Leishmania, but rather contributes to the survival of the protozoan in the
      environment of the insect midgut.

PMID- 1348599
TI  - A scanning electron microscopic study of the sporogonic development of Plasmodium
      falciparum in Anopheles stephensi.
AB  - The full development of Plasmodium falciparum in Anopheles stephensi mosquitoes
      was studied by scanning electron microscopy. Ookinetic development was described
      from in vitro cultures. Growing oocysts beneath the basal lamina of the midgut
      wall mechanically stretch this lamina until it is torn and displaced by day 7. In
      young oocysts the wall appears smooth. In older oocysts wrinkles in the wall are
      visible after routine fixation. Osmium tetroxide postfixation greatly reduced the
      occurrence of these wrinkles. Intracapsular development of sporozoites was
      visualized after mechanical manipulation of the oocysts during sample
      preparation. In contrast to P. berghei, no ectopic development was seen in P.
      falciparum in the mosquito midgut. The mechanism of sporozoite escape from the
      oocyst appears to be similar to that described for rodent malaria. Fracturing of
      salivary glands provided the first view by scanning electron microscopy of
      sporozoites located in proximal and distal gland cells and in the draining duct.

PMID- 1348598
TI  - Trypanosomiasis in cattle in Gambia: incidence, prevalence and tsetse challenge.
AB  - The incidence of trypanosome infections, measured by a Berenil Index in
      experimental herds of 10 Zebu and 10 N'Dama cattle, was compared with tsetse
      challenge and with the prevalence of parasitaemia in local N'Dama at three
      villages in Gambia. Tsetse challenge was more strongly correlated with the
      incidence of parasitaemia in the Zebu than in the N'Dama. There was a strong
      correlation between prevalence and incidence of infection in the N'Dama. There
      was no correlation, however, between prevalence of infection in cattle and tsetse
      challenge unless the data were offset by 3-5 months. The Berenil Index in the
      Zebu increased at about twice the rate as in the N'Dama under corresponding
      levels of challenge. It is concluded that whereas incidence of infection in
      susceptible animals is best measured independently, it can, under stable
      conditions, be inferred from an assessment of tsetse challenge.

PMID- 1348600
TI  - Chemical composition of Litomosoides carinii microfilarial sheaths.
AB  - Litomosoides carinii microfilariae were exsheathed by freezing and thawing, and
      the sheaths were separated by filtration. Samples of pure sheaths thus obtained
      were hydrolyzed, methanolyzed or oxidized with nitric acid under pressure at 300
      degrees C, respectively, and were analyzed for amino acids, sugars, fatty acids
      or for metal ions and phosphorus. Almost 75% of the sheath dry weight could thus
      be accounted for. Amino acids (55 weight %) were the major constituents, and
      amongst these glutamine and proline (approximately 11% each). The detection of 2%
      cysteine/cystine indicated the possible presence of disulfide crosslinks. Besides
      amino acids, approximately 8% of sugars--roughly equimolar amounts of (N
      acetyl)galactosamine and uronic acids--1.5% of monovalent cations (Na+ and K+)
      and 9.5% of phosphate were detected. No appreciable amounts of fatty acids,
      neutral sugars, neuraminic acid, or (N-acetyl)glucosamine (i.e. no chitin) were
      found.

PMID- 1348601
TI  - The rapid development of drug-resistance by Trypanosoma evansi in
      immunosuppressed mice.
AB  - The effect of immunosuppression on the development of drug resistance by
      trypanosomes was investigated in mice infected with Trypanosoma evansi. As a
      result of frequent passage in immunosuppressed mice given subcurative drug
      treatments clones of T. evansi rapidly developed high levels of resistance to mel
      Cy, diminazene aceturate and isometamidium chloride. Similar protocols in normal
      immunocompetent mice infected with the same parent clones did not lead to the
      development of drug-resistance. The resistant populations developed in
      immunosuppressed mice maintained their high levels of resistance when tested in
      normal mice. The mel Cy resistant clone was tested for cross-resistance to other
      trypanocides and was found to be also highly resistant to diminazene and
      pentamidine. The results indicate that impairment of the host immune system may
      lead to the rapid development of drug-resistance by T. evansi under experimental
      conditions in mice and may possibly play a role in the development of drug
      resistance by trypanosomes in the field.

PMID- 1348602
TI  - Evaluation of recombinant trypomastigote surface antigens of Trypanosoma cruzi in
      screening sera from a population in rural northeastern Brazil endemic for Chagas'
      disease.
AB  - A perfect serologic test for infection with Trypanosoma cruzi does not exist.
      This study uses recombinant T. cruzi surface proteins in the antibody capture
      enzyme linked immunoabsorption assay (ELISA); and compares this approach to the
      more standard immunofluorescence assay (IFA). Three recombinant antigens are
      studied: F1-160 corresponding to the 160 kDa flagellar associated surface protein
      of trypomastigotes (the motile form of T. cruzi in mammalian infections); and SA
      85-1.1 and 1.2 corresponding to different members of the 85 kDa family of surface
      proteins expressed by trypomastigotes and amastigotes (the replicative, non
      motile form of T. cruzi in mammalian infections). Each recombinant antigen is
      found to be highly specific (range 86-94%) but relatively insensitive (range 36
      52%) when used to screen for antibodies to T. cruzi. Defining seropositivity as
      reactivity to any of the three recombinant antigens markedly increases the
      sensitivity (72%) with only a minor reduction in specificity (82%). Thus,
      employing recombinant T. cruzi antigens to screen for T. cruzi infection has
      promise, but improvements in sensitivity must be made before widespread
      utilization is recommended.

PMID- 1348603
TI  - Preliminary efficacy trial of Cymelarsan, a novel trypanocide, in camels
      naturally infected with Trypanosoma evansi in Kenya.

PMID- 1348604
TI  - [Usefulness and safety of bunazosin hydrochloride in neurogenic bladder after
      prolonged administration].
AB  - Bunazosin hydrochloride (Ea-0643), a selective alpha 1-blocker, was administered
      to 14 patients with neurogenic bladder over prolonged periods of time in order to
      determine its efficacy and safety. Subjective symptoms were classified into 4
      grades, and their response assessed after 12 weeks of treatment. The proportion
      of patients showing improvement by at least one grade was 50.0% for retarded
      urination, 16.7% for prolonged urination, 25.0% for urinary stream condition,
      25.0% for abdominal pressure at voiding, and 28.6% for residual urine. Objective
      symptoms were also assessed after 12 weeks of treatment, and a statistically
      significant improvement was recognized in the volume of spontaneously voided
      urine, the maximum and mean flow rates on uroflowmetry. It should be noted that
      both of those flow rates had improved significantly only 2 weeks into the
      treatment. The degree of improvement in subjective and objective symptoms and the
      degree of general improvement were all higher at week 12 than at week 2 of
      treatment. Current knowledge of the mechanism of action of this drug, coupled
      with the observations made in this study, suggests that, once it has improved the
      urodynamics, it exhibits a sustained effect for prolonged periods of treatment.
      However, further studies are warranted concerning the mechanisms of the
      pharmacological action of the drug from a pathological viewpoint. The proportion
      of patients in whom Ea-0643 was judged to be useful at 12 weeks of treatment was
      41.7%, but when the assessment of 'slightly useful' was taken into consideration,
      the usefulness rate rose as high as 91.7%. Stomatitis was observed in only one
      case as a side effect of this drug.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348605
TI  - AZT and ddC work better together than alone.

PMID- 1348607
TI  - QT Prolongation and Ventricular Arrhythmias. International symposium. Nagasaki,
      Japan, February 8-9, 1991.

PMID- 1348606
TI  - Various cell types in human atherosclerotic lesions express ICAM-1. Further
      immunocytochemical and immunochemical studies employing monoclonal antibody 10F3.
AB  - The specificity of monoclonal antibody 10F3, generated to smooth muscle cells
      isolated from fetal human aorta, has been further explored in a series of
      biological, biochemical, and immunocytochemical studies. In the first assay, it
      was found that 10F3 could inhibit aggregation of phytohemagglutinin (PHA)-induced
      lymphocytes in a manner comparable to that of antibody RR1/1, an anti
      intercellular adhesion molecule 1 (ICAM-1) monoclonal antibody. In
      immunoprecipitation experiments followed by one-dimensional gel electrophoresis,
      both 10F3 and RR1/1 immunoprecipitated 90 kd proteins, with results suggesting
      that the two antibodies recognized different epitopes of the same molecule. A
      series of immunocytochemical studies on human atherosclerotic lesions was
      performed; using single-labeling techniques, 10F3-positive cells were found in
      the vessel wall and in lesions of virtually all specimens of fatty streaks and
      fibrous plaques. Using double-labeling techniques, 10F3-positive macrophages and
      10F3-positive smooth muscle cells were found; however, there were also a
      significant number of non-smooth muscle, nonmacrophage 10F3-positive cells. These
      studies demonstrate that 10F3 identifies ICAM-1, and that this protein is
      expressed on a variety of cell types in human atherosclerotic lesions. ICAM-1 may
      represent a developmentally regulated protein that is expressed in fetal but not
      adult mesenchymal cells, but can be re-expressed in pathologic processes such as
      atherosclerosis.

PMID- 1348608
TI  - Clinical aspects of the idiopathic long QT syndrome.

PMID- 1348609
TI  - Pathogenesis and therapy of the idiopathic long QT syndrome.

PMID- 1348610
TI  - Experimental QT interval prolongation.

PMID- 1348611
TI  - Ionic current mechanisms generating vertebrate primary cardiac pacemaker activity
      at the single cell level: an integrative view.

PMID- 1348612
TI  - The somatostatin receptor in the GI tract.

PMID- 1348613
TI  - Mechanisms for anoxic survival in the vertebrate brain.
AB  - When energy supplies to the mammalian brain are significantly reduced by anoxia,
      for a very short time energy requirements are curtailed by such routes as the
      suppression of synaptic transmission, while energy supply is enhanced by an
      increase in cerebral blood flow and an increase in glycolysis. The reduction of
      ATP consumption is insufficient to match the greatly curtailed supply of ATP
      coming from anaerobic glycolysis and the hydrolysis of PCr, and within minutes
      ATP falls, there is a loss of ion homeostasis with depolarization, and cell death
      occurs. The anoxia-tolerant species, like the turtle, appear to employ similar
      mechanisms to reduce energy expenditure, but in addition to such means as
      increases in inhibitory neurotransmitters and the manipulation of ion channel
      activities, they are able to reduce the energy costs to a level that can be met
      by a greatly reduced supply from anaerobic glycolysis. In this way ATP levels are
      maintained for many hours, and anoxic depolarization, with its concomitant
      consequences such as an uncontrolled release of excitatory amino acids are
      avoided. The greater anoxic tolerance of the mammalian neonate brain is due in
      part to intrinsic lower metabolic requirements and, perhaps through mechanisms
      similar to those in the turtle, to suppress metabolic demand. Studies of the
      survival mechanisms of anoxia-tolerant brains of such species as the turtle and
      crucian carp are not only of value for investigating a remarkable neuronal
      adaptation, but they promise to provide a valuable model for the study of the
      etiology of hypoxic damage and survival strategies in the mammal.

PMID- 1348614
TI  - Solving solution structures of physiologically relevant proteins by NMR
      spectroscopy.

PMID- 1348615
TI  - [Takayasu arteritis associated with heart valve diseases (pulmonary and aortic)
      and arteritis (coronary and renal)].
AB  - The most severe arteritis due to Takayasu's disease are those related to renal
      and coronary arteries. The first one because it produces severe arterial
      hypertension and the second one because it puts the patient in high risk of
      suffering either myocardial ischemia or infarction. These situations worsen when
      this entity is associated to valvular heart lesions. The authors present the
      clinical cases of two female patients with Takayasu's disease. One of them in
      acute phase of the illness, where coronary arteritis, mild coarctation of the
      aorta, right pulmonary artery stenosis, and pulmonary valve stenosis were
      present. The second patient was seen during the remission phase of the disease
      with obstruction of the left subclavicular artery, renal arteritis, severe
      arterial hypertension and aortic valve insufficiency. The authors discuss the
      prognosis of patients with Takayasu's disease associated to valvular heart
      disease and its role in the etiology of pulmonary valvular stenosis. Finally, the
      authors point out the importance of recognizing the active and non active phases
      of the Takayasu's disease in relation of the adequate stage for surgical
      treatment of the lesions caused by this disease.

PMID- 1348616
TI  - [How to evaluate the cost/effectiveness ratio of different therapies of coronary
      disease].
AB  - The results of epidemiologic studies on the efficacy of different strategies of
      prevention or improvement of the prognosis of coronary artery disease are
      generally expressed in terms of percentage reduction of risk; for example, the
      treatment of hypercholesterolaemia reduces the risk of coronary death by 21%. In
      order to improve the assessment of the efficacy of these approaches the authors
      propose to take into account the number of subjects which needs to be treated
      each year to prevent one cardiovascular event more than the control group (for
      example, in hypercholesterolaemia, 1,736 patients). This number depends on the
      reduction of risk and also on the incidence of complications in the control
      group. Using this method, the authors classified different therapeutic strategies
      in order of their efficacy: thrombolytic therapy in the acute phase of myocardial
      infarction, then aortocoronary bypass grafting of left main coronary or triple
      vessel disease, secondary prevention with stopping smoking, and betablocker
      therapy. Finally, primary prevention with anti-smoking campaigns, treatment of
      hypertension and hypercholesterolemia. Based on this figure and knowing the
      annual cost of patient treatment, it is possible to calculate a cost
      effectiveness ratio for each of these therapeutic interventions.

PMID- 1348617
TI  - Characterization of a new compound, S35b, as a guanylate cyclase activator in
      human platelets.
AB  - The effects of S35b (4-methyl-3-phenyl sulfonylfuroxan), a new phenyl
      sulfonylfuroxan compound, were investigated on human platelets activated by
      different agonists. Platelet aggregation evoked by arachidonic acid (AA),
      collagen, ADP and thrombin was inhibited by the drug in a dose-dependent manner.
      S35b inhibited the AA-induced increase of cytosolic free Ca2+ ([Ca2+]i) and
      production of malondialdehyde. A primary action of the compound on cyclooxygenase
      is unlikely since: (1) U-46619 (15s-hydroxy-11,9-[epoxymethano]-prosta-5Z,13E
      dienoic acid, a stable epoxymethano analog of prostaglandin H2) could not reverse
      the inhibitory effect of S35b on AA-induced aggregation and [Ca2+]i increase; (2)
      U-46619-induced aggregation and [Ca2+]i rise were inhibited by S35b; and (3) at
      high collagen concentrations platelet aggregation (which is unresponsive to
      aspirin under such conditions) was blocked by S35b as well. Thus the drug action
      is likely to be exerted at an early step of the platelet activation pathway. The
      elevation in the platelet cGMP level evoked by S35b in a time- and concentration
      dependent manner can account for the inhibitory effect: increased cGMP levels
      could interfere, for instance, with G protein-phospholipase C coupling and
      subsequent phosphoinositide hydrolysis.

PMID- 1348618
TI  - Antimalarial activity of orotate analogs that inhibit dihydroorotase and
      dihydroorotate dehydrogenase.
AB  - Dihydroorotase and dihydroorotate dehydrogenase, two enzymes of the pyrimidine
      biosynthetic pathway, were purified from Plasmodium berghei to apparent
      homogeneity. Orotate and a series of 5-substituted derivatives were found to
      inhibit competitively the purified enzymes from the malaria parasite. The order
      of effectiveness as inhibitors on pyrimidine ring cleavage reaction for
      dihydroorotase was 5-fluoro orotate greater than 5-amino orotate, 5-methyl
      orotate greater than orotate greater than 5-bromo orotate greater than 5-iodo
      orotate with Ki values of 65, 142, 166, 860, 2200 and greater than 3500 microM,
      respectively. 5-Fluoro orotate and orotate were the most effective inhibitors for
      dihydroorotate dehydrogenase. In vitro, 5-fluoro orotate and 5-amino orotate
      caused 50% inhibition of the growth of P. falciparum at concentrations of 10 nM
      and 1 microM, respectively. In mice infected with P. berghei, these two orotate
      analogs at a dose of 25 mg/kg body weight eliminated parasitemia after a 4-day
      treatment, an effect comparable to that of the same dose of chloroquine. The
      infected mice treated with 5-fluoro orotate at a lower dose of 2.5 mg/kg had a
      95% reduction in parasitemia. The effects of the more potent compounds tested in
      combination with inhibitors of other enzymes of this pathway on P. falciparum in
      vitro and P. berghei in vivo are currently under investigation. These results
      suggest that the pyrimidine biosynthetic pathway in the malarial parasite may be
      a target for the design of antimalarial drugs.

PMID- 1348619
TI  - Effects of deoxyspergualin on dipeptidyl peptidase-II and -IV in the spleen of
      BXSB mice and MRL/lpr mice during the development of the lupus erythematosus-like
      syndrome.

PMID- 1348621
TI  - Clinical interactions with alpha-2-adrenergic agonists in anesthetic practice.
AB  - With the continued use of alpha-2-adrenergic agonists in anesthetic practice,
      careful attention should be given to the potential for drug interactions. Based
      on a review of the basic and applied pharmacology of this class of compound, we
      have made recommendations for the safe and efficacious use of alpha-2-adrenergic
      agonists in the clinical setting.

PMID- 1348620
TI  - Facilitation of rapid-sequence intubation with large-dose vecuronium with or
      without priming.
AB  - STUDY OBJECTIVES: To determine the effect of priming on the intubation and onset
      times of vecuronium 0.3 mg/kg. DESIGN: Randomized, unblinded study. SETTING:
      Operating rooms and postanesthetic recovery unit of a university-affiliated
      general hospital. PATIENTS: Thirty female ASA physical status I and II patients
      scheduled for intraperitoneal surgery divided into two groups of 15 each.
      INTERVENTIONS: Anesthesia was induced and maintained with sufentanil, droperidol,
      thiopental sodium, and nitrous oxide in oxygen. Patients in Group 1 were given
      vecuronium 0.015 mg/kg 4 minutes before induction and vecuronium 0.285 mg/kg 1
      minute after induction. Patients in Group 2 received a single 0.3 mg/kg dose of
      vecuronium 1 minute after thiopental sodium. The ulnar nerve was stimulated every
      10 seconds with train-of-four supramaximal impulses of 0.2 millisecond duration
      at 2 Hz. The compound electromyogram (EMG) of the adductor pollicis was
      continuously recorded. The trachea was intubated when the amplitude of the EMG
      decreased to 15% to 25% of control. At the end of surgery, residual neuromuscular
      block was reversed with edrophonium 0.75 mg/kg. MEASUREMENTS AND MAIN RESULTS:
      All patients in Group 1 could be intubated in 80 seconds or less, and the longest
      onset time was 120 seconds. In Group 2, the longest intubation time was 140
      seconds, and the longest onset time was 200 seconds. Clinical durations in both
      groups were unpredictable, ranging from 47 to 185 minutes in Group 1 and from 63
      to 160 minutes in Group 2. Ten of the 30 patients required an additional 0.5
      mg/kg of edrophonium for antagonism of the residual neuromuscular block. There
      were no significant changes in heart rate or blood pressure attributable to
      vecuronium. CONCLUSIONS: Seventy-five percent to 85% neuromuscular block of the
      adductor pollicis, required for atraumatic tracheal intubation, developed in 80
      seconds or less when vecuronium 0.3 mg/kg was administered in divided doses and
      in 140 seconds or less when it was injected as a single bolus dose. Clinical
      duration of vecuronium 0.3 mg/kg is long and unpredictable, and reversal of
      residual neuromuscular block may require larger doses of anticholinesterases. It
      is recommended that an intubating dose of vecuronium 0.3 mg/kg be used only in
      patients undergoing long surgical procedures that require prolonged
      postanesthetic mechanical ventilation.

PMID- 1348622
TI  - The cerebroside sulfate activator from pig kidney: derivitization, cerebroside
      sulfate binding, and metabolic correction.
AB  - Highly purified cerebroside sulfate activator from pig kidneys was characterized
      by a number of chemical and biological procedures. Methods for chemical
      modifications were evaluated in an attempt to obtain biologically active
      derivatives. Iodination, dabsylation, and to a lesser degree reductive
      methylation provided useful products with good retention of cerebroside sulfate
      activator activity. Other procedures resulted in largely inactive derivatives or
      losses in both protein and biological activities. Attempts at renaturation of
      cerebroside sulfate activator subjected to various denaturing conditions appeared
      to be successful in many instances, but it was uncertain if the protein structure
      had actually been disrupted. The binding of cerebroside sulfate by activator was
      estimated by gel filtration under conditions similar to those of its assay. The
      formation of a relatively stable 1:1 complex was observed, collaborating results
      with the human protein. The complex was stable enough to be isolated and shown to
      be an efficient substrate for arylsulfatase A. The effectiveness of the pig
      kidney cerebroside sulfate activator for correcting the metabolic defect in
      activator-deficient human fibroblasts was compared with human materials. The pig
      kidney protein was taken up more efficiently by the cells and resulted in a
      better metabolic correction than material from human liver, but was somewhat less
      effective than a preparation from human urine.

PMID- 1348624
TI  - Recent advances in steroid biochemistry and molecular biology. Proceedings of the
      10th International Symposium of the Journal of Steroid Biochemistry and Molecular
      Biology. Paris, France, 26-29 May 1991.

PMID- 1348623
TI  - P-glycoprotein overexpression cannot explain the complete doxorubicin-resistance
      phenotype in rat glioblastoma cell lines.
AB  - We have associated pharmacological studies to a semi-quantitative evaluation of P
      glycoprotein(s) expression, to establish if classical multidrug resistance (MDR)
      could account for the complete resistance phenotype exhibited by progressively
      doxorubicin-resistant rat glioblastoma cells. Three resistant variants (C6 0.001,
      C6 0.1 and C6 0.5) of the C6 glioblastoma cell line (C6 S) were selected by long
      term culture in the presence of three concentrations of doxorubicin (0.001, 0.1
      and 0.5 microgram.ml-1 respectively). The degree of doxorubicin resistance was
      respectively 7, 33 and 400, and all the cell variants were cross-resistant to m
      AMSA, etoposide and vincristine. Doxorubicin incorporation was reduced similarly
      in all resistant cells, irrespective of the level of resistance. When exposed to
      their respective doxorubicin IC50, the 7-fold resistant cells had the same
      intracellular drug incorporation as the sensitive cells, whereas the 33-fold and
      400-fold resistant cells could incorporate respectively 3.7 and 17 times more
      drug. The ratio of doxorubicin exposures required for 50% DNA synthesis
      inhibition and 50% growth inhibition was dependent on the degree of resistance;
      this ratio was 12.8 in C6 S, 11.6 in C6 0.001, 6.3 in C6 0.1 and 1.8 in C6 0.5. P
      glycoprotein(s) overexpression was of the same magnitude as the resistance factor
      in variants C6 0.001 and C6 0.1, but was lower than resistance factor in variant
      C6 0.5. Reversal of drug incorporation by verapamil was complete in all resistant
      cell lines; however, reversal of doxorubicin cytotoxicity was complete only in
      the 7-fold resistant line and was only partial in the most resistant lines, which
      remained 10-fold and 20-fold resistant to doxorubicin. These results suggest that
      classical MDR was the first phenotype selected by doxorubicin in C6 0.001,
      whereas mechanism(s) of doxorubicin resistance other than classical MDR are added
      in the most resistant lines.

PMID- 1348625
TI  - Germ cell-Sertoli cell interactions and production of testosterone by purified
      Leydig cells from mature rat.
AB  - The addition of seminiferous tubule (ST) culture medium (STM) prepared from
      testes of either busulfan-treated (Bus) or cryptorchid (Cryp) or genetically
      sterile (hd) rats, to Percoll purified Leydig cells leads to a further increase
      of LH-stimulated testosterone (T) output (26, 43 and 14%, respectively). Taking
      into account that the Sertoli cell number per cm of ST is 2.6, 1.8 and 1.4-fold
      greater in Bus, Cryp and hd rats than in controls, the above STM effects on T
      output, expressed per 10(6) Sertoli cells are in fact lower (63, 44 and 43%,
      respectively) that those of control STM. Similar results have been obtained for
      the STM transferrin levels which are decreased, 74, 67 and 45%, respectively in
      Bus, Cryp and hd animals. So, it is likely that the Sertoli cell secretion of
      both the paracrine factor involved on Leydig cell T production and the
      transferrin is influenced mainly by spermatids and to a lesser extent by
      spermatocytes of mature rat testis.

PMID- 1348626
TI  - Duration of antagonizing effect of RU486 on the agonist induction of tyrosine
      aminotransferase via glucocorticoid receptor.
AB  - The duration of the antagonizing activity of RU486 on tyrosine aminotransferase
      (TAT) induction and the glucocorticoid receptor in rat liver was studied. A
      single dose of RU486 (10 mg/kg) caused occupation of the cytosol glucocorticoid
      receptor in rat liver at 1 h. During this time no nuclear binding of
      [3H]dexamethasone ([3H]Dex) receptor complex was recorded, and TAT induction was
      completely blocked. TAT inducibility recovery parallelled receptor binding in
      both the cytosol and the nuclei, reaching maximum at 12 h. In contrast, nuclear
      binding recovered in 24 h, and [3H]Dex receptor binding in cytosol 48 h after
      RU486 application. It is concluded that the inhibitory effect of a single dose of
      RU486 on TAT induction is of rather short duration. At concomitant presence of
      agonist and antagonist in vivo, no direct correlation between agonist receptor
      occupancy and TAT induction could be observed.

PMID- 1348627
TI  - Two liver-enriched trans-acting factors support the tissue-specific basal
      transcription from the rat tyrosine aminotransferase promoter.
AB  - The rat tyrosine aminotransferase gene (TAT) is a glucocorticoid-inducible gene,
      specifically expressed in liver. Using gel retardation assays, we have shown that
      its promoter (nt + 1 to -350; TAT.35) binds a combination of both ubiquitous and
      liver-specific trans-acting factors. Cis-acting sequences spanning: (i) nt -65 to
      -85 bound NF-Y, an ubiquitous "AACCAAT" box binding factor; (ii) nt -157 to -171
      bound a liver-enriched member of the NF1 gene family [NF1Liver (NF1L hereafter)];
      (iii) nt -266 to -281 bound the liver specific factor HNF1; and (iv) nt -283 to 
      288 bound ubiquitous "CCAAT" box binding factor(s). Moreover, the TAT gene
      promoter was able to drive liver-specific basal transcription, even in an in
      vitro assay using TAT-expressing (liver) vs non-expressing (spleen) crude nuclear
      extracts (NEs). Competition studies in transcription with both unmutated and
      mutated ds-oligonucleotides (ds-oligos) demonstrated that NF1L and HNF1 supported
      approx. 60 and 25% of the basal transcriptional activity sustained by TAT.35 in
      the liver, respectively. Neither of these oligos affected the very low level of
      transcription sustained by spleen NEs. This suggests a minor role for HNF1 in
      liver-specific basal TAT gene expression, consistent with previous observations
      with dedifferentiated C2 hepatoma cells (which does not express HNF1)
      [Deschatrette and Weiss. Biochimie 56 (1974) 1603-1611 and Cereghini et al. EMBO
      Jl9 (1990) 2257-2263]. Competition studies in liver-specific in vitro
      transcription with ds-oligo -265/-290 yielded a 90% inhibition, suggesting either
      that sequences spanning nt -283 to -288 sequester "CCAAT-box" binding factor(s)
      that may be relevant elsewhere for TAT promoter function (e.g. NF-Y which
      interacts with nt -65 to -85), or that such a factor interacts functionally with
      HNF1.

PMID- 1348628
TI  - Excitatory amino acid regulation of gonadotropin secretion: modulation by steroid
      hormones.
AB  - Excitatory amino acids (EAAs) can potently modulate gonadotropin secretion in the
      male rat and monkey. In the present study we examined the effect of EAAs on
      luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the female rat
      under low estrogen (ovariectomized) and high estrogen (proestrus) backgrounds. In
      ovariectomized immature female rats N-methyl-D-aspartate (NMDA) inhibited LH but
      not FSH secretion at 30 min post-injection. In contrast, NMDA potently stimulated
      LH but not FSH secretion when administered on proestrus to adult female rats.
      Both glutamate and kainate were also found to stimulate LH but not FSH secretion
      in estrogen-treated ovariectomized immature rats. This study suggests that EAA
      neurotransmission may be an important component in the expression of gonadotropin
      surges and that EAA effects appear to be subject to gonadal steroid regulation.

PMID- 1348629
TI  - Colocalization of vasoactive intestinal polypeptide and GABA immunoreactivities
      in a population of wide-field amacrine cells in the rabbit retina.
AB  - Vasoactive intestinal polypeptide (VIP) immunoreactive (IR) neurons in the rabbit
      retina constitute a population of wide-field amacrine cells. To better define
      this cell population, we examined the coexpression of VIP with other putative
      retinal transmitters or their biosynthetic enzymes, including gamma-aminobutryic
      acid (GABA), tyrosine hydroxylase (TH), and somatostatin (SRIF). Colchicine
      treated retinas were immersion fixed in 4% paraformaldehyde. The retinas were cut
      either perpendicular or parallel to the vitreal surface and processed by double
      label immunofluorescence techniques using antibodies directed to VIP, GABA, TH,
      and SRIF. The immunoreactive staining patterns obtained with these antibodies
      were the same as those described in previous studies. GABA-IR neurons were
      localized to the proximal inner nuclear layer (INL) and ganglion cell layer (GCL)
      and processes were distributed throughout the inner plexiform layer (IPL). TH-
      and SRIF-IR neurons were sparsely distributed to the proximal INL and GCL,
      respectively. TH-IR processes ramified in laminae 1, 3, and 5, and SRIF-IR
      processes in laminae 1 and 5 of the IPL. Colocalization experiments showed that
      all VIP-IR neurons contain GABA immunoreactivity. In contrast, colocalization of
      VIP and TH or SRIF immunoreactivities was never observed. These results
      demonstrate that VIP-IR wide-field amacrines of the rabbit retina make up a
      neurochemically and morphologically distinct subpopulation of the GABA-IR
      amacrine cell population. Furthermore, VIP-IR amacrine cells constitute a
      distinct group with respect to the TH- and SRIF-IR amacrine cells.

PMID- 1348630
TI  - Identification of distinct P-glycoprotein gene sequences in rat.
AB  - In higher vertebrates, P-glycoprotein is usually encoded by a small family of
      genes. We have determined that the rat contains three P-glycoprotein genes and
      have cloned distinct genomic fragments containing the putative 3' untranslated
      regions of these P-glycoprotein genes. Sequence analysis indicates that the rat P
      glycoprotein genes belong to the three P-glycoprotein classes identified in
      mammals. These cloned sequences will be useful for delineating the expression of
      P-glycoprotein genes in the rat. We have also isolated a fourth clone which
      contains only a short, but highly conserved P-glycoprotein domain. This clone
      appears not be a member of the P-glycoprotein gene family, and its relationship
      to P-glycoprotein is unknown.

PMID- 1348632
TI  - Drug addiction and AIDS: highlights of the 1st European Congress.
AB  - The 1st European Congress on 'Drug Addiction and AIDS' was held in Vienna,
      Austria, February 21-23 1991. This conference represented scientists from all
      areas of Europe and North America. The co-ordinators and the international
      scientific board offered an exciting programme with eight workshops in clinical,
      medical and management tracts; there were four plenary sessions with
      international, national and local experts, exhibits and receptions. With the
      impact of AIDS and the changes in Eastern Europe, we must now, more than ever
      before, rethink our strategies to improve effective treatment for substance
      abusing patients.

PMID- 1348631
TI  - Analysis of the 5' flanking region of the rat proliferating cell nuclear antigen
      (PCNA) gene.
AB  - The proliferating cell nuclear antigen (PCNA), highly conserved among eukaryotes,
      is an auxiliary factor for DNA polymerase delta. In this report we sequenced 1560
      nucleotides (nt) of the 5' flanking region of the rat PCNA gene and located the
      transcription initiation site. The sequence contains 1435 nt upstream of the cap
      site and promotes transcription of a linked heterologous reporter gene in rat,
      mouse and human cells. Transient expression assays using a series of 5' deletion
      mutants revealed that 240 nt of the upstream sequence are sufficient for full
      promoter activity. Three GC boxes and several other binding sites of
      transcription factors were observed, but neither a TATA nor a CCAAT sequence was
      found in this region. The results also suggested the existence of a negative
      regulatory element(s) between -968 and -691. Cotransfection with early region 1
      (E1) genes of human adenoviruses activated the expression of the reporter gene,
      suggesting that an E1-responsive element is located at the proximal promoter
      region within 81 nt upstream of the transcription initiation site.

PMID- 1348633
TI  - Prediction of outcome after first recurrence of breast cancer.
AB  - OBJECTIVE: To assess the independent power of certain clinical, histological, and
      morphometric variables to predict survival after first recurrence of breast
      cancer. DESIGN: Long term follow up study. SETTING: Departments of surgery and
      pathology, University Hospital. SUBJECTS: 212 patients (from a consecutive series
      of 517) who developed recurrence after primary treatment of breast cancer between
      1968 and 1990. INTERVENTIONS: Re-examination of histology of primary tumours,
      follow up of patients, and calculation of predictive score by Cox's regression
      analysis. RESULTS: The nodal status at the time of diagnosis (p less than 0.001),
      the SD of the nuclear area (p = 0.01), the degree of tubule formation (p =
      0.003), and the age of patient, were all independent predictors. The most
      important predictor of survival was the prognostic score derived from the
      coefficients of the Cox's model (p less than 0.0001). CONCLUSION: Survival after
      first recurrence can be accurately predicted by advanced histological analysis of
      the primary tumour tissue. Combination of independent predictors permits even
      more accurate estimation of survival time.

PMID- 1348634
TI  - Increasing prevalence of abdominal aortic aneurysms. A necropsy study.
AB  - OBJECTIVE: To analyse the prevalence of abdominal aortic aneurysms in the city of
      Malmo. DESIGN: Retrospective demographic study. SETTING: Malmo General Hospital.
      MATERIAL: Reports of all 45,838 necropsies done at the Department of Pathology,
      Malmo General Hospital 1958-1986. RESULTS: Abdominal aortic aneurysms were found
      in 4,300/100,000 men and 2,100/100,000 women. The mean annual age-standardised
      increase of aortic aneurysmal disease was 4.7% among men and 3.0% among women.
      The prevalence among men increased rapidly after the age of 55 and reached a peak
      of 5.9% at the age of 80; that among women increased after the age of 70 and
      reached a peak of 4.5% above the age of 90 years. CONCLUSION: The prevalence of
      aortic aneurysmal diseases has increased during the last three decades, and is
      age and sex-dependent.

PMID- 1348635
TI  - A "new" intraabdominal artery. The pedicled right gastroepiploic artery for
      myocardial revascularization.
AB  - The right gastroepiploic artery (GEA) was used as a pedicled conduit for direct
      coronary artery revascularization in 20 patients presenting with more or less
      exhausted saphenous vein resources. The early angiographic patency of the GEA
      conduit appears to be satisfactory when it is connected to the right coronary
      artery system. A distinct disadvantage of GEA grafting is the necessity to enter
      the abdominal cavity, which may lead to probably rare and as yet unrecognized
      morbidity. Future abdominal surgery may injure the GEA conduit unless its
      topographic relations to the prepyloric antrum, liver and diaphragm are properly
      recognized. The surgeon must then be prepared to encounter antegastric,
      retrogastric, antehepatic, transhepatic and retrohepatic routes of the redirected
      intraabdominal artery. The present paper addresses this problem. Preoperative
      angiography of the celiac trunk and superior mesenteric artery may be helpful in
      decision-making when a patient reports or records show that a graft has been
      harvested from the abdominal cavity.

PMID- 1348636
TI  - Laser hepatorrhaphy in albino rats.
AB  - The ability of low-power Nd-YAG laser to weld liver tears was studied in nine
      albino rats (average body weight 146 g) after induction of 11 liver tears. Laser
      hepatorrhaphy was successful in ten tears. Haemostasis was achieved with the
      laser technique in all 11 tears, including the single case of postoperative liver
      tear dehiscence. Bleeding from the site of a marker stitch was successfully
      controlled by two additional laser shots in one animal. Histologic studies of
      successfully welded liver tears were done on the first and third postoperative
      days.

PMID- 1348637
TI  - Style and substance: maintaining a balance.

PMID- 1348638
TI  - Prevention of peritoneal adhesions in rats with verapamil, hydrocortisone sodium
      succinate, and phosphatidylcholine.
AB  - OBJECTIVE: To assess the effectiveness of verapamil, hydrocortisone sodium
      succinate, and phosphatidylcholine in the prevention of experimental adhesions.
      DESIGN: Randomized trial. MATERIAL: 80 rats. INTERVENTIONS: Laparotomy and
      intraperitoneal irrigation with saline 40 degrees C, then verapamil hydrochloride
      1 mg/kg intravenously 15 min before, during, and after irrigation; or
      hydrocortisone sodium succinate 50 mg/kg intravenously half an hour before
      irrigation; or phosphatidylcholine 5.5 mg/kg orally eight days before and seven
      days after irrigation plus 0.5 mg/ml in the irrigation fluid; or no further
      intervention. MAIN OUTCOME MEASURES: Development of adhesions two weeks after
      irrigation, and completeness of wound healing. RESULTS: Adhesions developed in 13
      of 19 control animals; 7 of 20 that were given verapamil; 6 of 20 that were given
      hydrocortisone; and 3 of 20 given phosphatidylcholine. CONCLUSION: Adhesions that
      developed in rats after laparotomy and intraperitoneal irrigation with saline at
      40 degrees C can be significantly reduced by phosphatidylcholine.

PMID- 1348639
TI  - Diagnostic accuracy and perforation rate in appendicitis: association with age
      and sex of the patient and with appendicectomy rate.
AB  - OBJECTIVE: To see if diagnostic accuracy and perforation rate in acute
      appendicitis is associated with age and sex of the patients and with the
      appendicectomy rate. DESIGN: Retrospective study of consecutive patients from a
      defined population. Study of associations between diagnostic accuracy and
      perforation rate and appendicectomy rate in published reports. SETTING: Jonkoping
      county, Sweden. SUBJECTS: 3,029 patients operated on for suspected acute
      appendicitis from 1984-1989. MAIN OUTCOME MEASURES: Findings at laparotomy for
      acute appendicitis, confirmed with histological examination in 83% of the cases.
      RESULTS: Diagnostic accuracy was low at the extremes of age and in women (60%
      compared with 79% in men, p less than 0.001). When all intra-abdominal conditions
      were considered the percentage of negative laparotomies among women (24%) was
      twice that among men (12%, p less than 0.001). This difference between the sexes
      was also seen in nonfertile ages. Perforation rate was higher among men (18%
      compared with 13%, p less than 0.01) and at extremes of age. According to
      correlation analysis of published reports the perforation rate is unrelated to
      either diagnostic accuracy or appendicectomy rate while diagnostic accuracy is
      inversely associated with the appendicectomy rate. CONCLUSION: A low diagnostic
      accuracy is a problem mainly at extremes of age and in females. A low
      appendicectomy rate is associated with a high diagnostic accuracy, while the
      perforation rate is unaffected. A conservative attitude to exploration therefore
      seems justified.

PMID- 1348640
TI  - Effect of appendicectomy on development of right inguinal hernia.
AB  - The effect of appendicectomy on the subsequent development of right inguinal
      hernia was investigated in 583 patients with hernias, 42 of whom had previously
      had appendicectomies. The incidence of right sided hernias was no greater among
      these patients than among those who had not had their appendixes removed. Neither
      sex was more prone to develop an inguinal hernia after appendicectomy, and no
      type of hernia (direct or indirect) predominated. The cause of right sided
      inguinal herniation after appendicectomy has been thought to be damage to the
      nerve supply of the inguinal muscles during the appendicectomy incision. All our
      42 cases except two had had their appendicectomies through classic McBurney
      incisions, which were some distance away from the most common areas of nerve
      damage. We conclude that development of a right inguinal hernia is an unlikely
      complication of appendicectomy if a classic McBurney incision was used.

PMID- 1348641
TI  - Effect of epidural and general anaesthesia compared with general anaesthesia
      alone in large bowel anastomoses. A prospective study.
AB  - OBJECTIVE: To find out whether patients did better after operations that entailed
      a large bowel anastomosis if they were given combined epidural and general
      anaesthesia with spontaneous ventilation rather than standard general anaesthesia
      with muscle relaxation and ventilation. DESIGN: Prospective randomised trial.
      SETTING: Specialist unit, teaching hospital. SUBJECTS: 80 patients undergoing
      large bowel anastomoses. MAIN OUTCOME MEASURES: Incidence of chest infection,
      wound infection, anastomotic breakdown, urinary tract infection, deep vein
      thrombosis, pulmonary embolism, median hospital stay and death. RESULTS: There
      were no differences between the groups, but the results were better during the
      trial period (1985-89) than during the period 1978-83. CONCLUSION: Factors that
      influence anastomotic healing are complex and improved surgical techniques,
      postoperative monitoring and patient care may account for the improvement in
      results compared with the earlier period.

PMID- 1348642
TI  - Anorectal abscesses in immunosuppressed patients.
AB  - The results of surgery in 14 immunosuppressed patients with 17 anorectal
      abscesses are presented. Abscess incision was followed by almost immediate relief
      of pain. Healing was obtained in 15 cases, but two patients died of causes
      unrelated to surgery. Symptoms, therapeutic possibilities and prognosis are
      discussed. The authors conclude that surgery should be performed in all cases to
      prevent development of septicemia. Fluctuation should not be awaited, but surgery
      should be minimized if granulocyte and platelet counts are low. Each patient must
      be managed individually, according to the nature of malignant disease, general
      state of health and degree of immunosuppression. Antibiotic cover is important,
      and primary closure of the abscess cavity should never be attempted.

PMID- 1348643
TI  - Resection of liver gastrinoma leading to persistent eugastrinemia. Case report.
AB  - In a 30-year-old man with Zollinger-Ellison syndrome, the only detectable
      gastrinoma was in the right liver lobe. Removal of the lobe, without additional
      gastric surgery, was followed by normalization of the gastrin level. Long-term
      follow-up confirmed the good result. The usefulness of quick intraoperative
      gastrin assay is stressed.

PMID- 1348644
TI  - Septic pulmonary emboli after prolonged use of central venous catheter for
      parenteral nutrition. Case report.
AB  - A 48-year-old man underwent total parenteral nutrition via a central venous
      catheter because of small bowel obstruction after the reconstruction of the
      abdominal aorta. Three weeks after, he developed septic emboli in the right lung,
      which was one of rare complications of central venous catheter.

PMID- 1348645
TI  - Eosinophilic gastroenteritis presenting as ascites. Case report.
AB  - A 46 year old man presented with a four week history of ascites and loss of
      weight. The diagnosis of eosinophilic gastroenteritis was made only after
      histological examination of a biopsy specimen taken at laparotomy. All other
      investigations had been unhelpful. He made a good recovery and was given no
      treatment.

PMID- 1348646
TI  - Extragenital endometriosis. A review.
AB  - Extragenital endometriosis is common and may be found in any tissue. The most
      pronounced symptoms are pain and local bleeding that usually (at least initially)
      are cyclical and more pronounced at the time of menstruation. The lesions often
      infiltrate neighbouring organs, and cause considerable fibrosis together with
      increasing symptoms. The patients have often had pain for many years, have been
      investigated at different clinics, and been given conflicting diagnoses, often of
      mental instability, before the correct diagnosis is finally made. The disease is
      difficult to diagnose clinically, and must be verified histologically. Often the
      endometriosis responds to treatment with hormones to inactivate the ovaries, but,
      sometimes the lesions are resistant, or respond too slowly, to drugs, and local
      excision is required. A gynaecologist should be called if the diagnosis is made
      at laparotomy or laparoscopy, to establish the extension of the endometriotic
      lesion and should be consulted about complementary investigations and hormonal
      treatment.

PMID- 1348648
TI  - Focus on fungal infections: an update on diagnosis and treatment. Phoenix,
      Arizona, 21-22 February 1991.

PMID- 1348647
TI  - Molecular determination of cell tropism of human immunodeficiency virus.
AB  - In the 10 years since AIDS was first identified, knowledge of the causative
      agent, human immunodeficiency virus (HIV), has advanced remarkably. Molecular
      biological analysis has had a greater impact on the investigation of HIV and AIDS
      than on that of any other disease. Unfortunately, the vast amount of material
      published on this subject has still not resulted in a thorough understanding of
      the pathogenesis of AIDS. Undoubtedly, part of the reason for the complexity of
      this disease stems from the ability of HIV to infect a large number of different
      cell types. To comprehend the mechanisms involved in the pathogenesis of AIDS, it
      is of great importance to understand the factors that control the cell tropism of
      the virus. In this review, we describe the known factors involved in the
      determination of the cell tropism of retroviruses and the ways by which molecular
      biological analysis of HIV has revealed the nature of the processes involved in
      control of the tropism of the virus for various cell types.

PMID- 1348649
TI  - The Bethesda system--the European perspective: report on the Second Conference on
      the Bethesda System for reporting cervical/vaginal cytological diagnoses.

PMID- 1348650
TI  - Peptic ulcer in cirrhotic patients: a short- and long-term study with
      antisecretory drugs.
AB  - The clinical course of gastric and duodenal ulcer and the efficacy of H2 blockers
      in ulcer healing and the prevention of relapse in cirrhotic liver patients were
      studied. Seventy-four cirrhotic patients with endoscopically proven acute gastric
      ulcer (30), duodenal ulcer (34) or a combination of both gastric and duodenal
      ulcers (10) were treated for six weeks with either Cimetidine 800 mg/daily (27)
      or Ranitidine 300 mg/daily (47). Of the 77 patients 49 (66.2%) were healed after
      therapy, 11 cases (14.8%) remained unhealed even after two additional cycles of
      the same treatment and four were lost to follow-up. After an endoscopically
      proven healing of the active ulcer, 51 patients took part in the long-term study
      over a mean period of 24 months: 21.5% of the 27 patients were treated with a
      maintenance dosage of H2 blockers and 29.1% of the 24 patients left without
      therapy relapsed during the first year. We conclude that the ulcer healing rate
      with H2 blockers is lower and the relapse rate higher in cirrhotic patients than
      in the general ulcer population.

PMID- 1348651
TI  - The Italian Association for the Study of the Pancreas (AISP) XV National
      Congress. Bologna, 3-4 April 1992. Abstracts.

PMID- 1348652
TI  - Proceedings of the international symposium celebrating the 30th anniversary of
      the discovery of calcitonin. Vancouver, Canada, August 29, 1991.

PMID- 1348653
TI  - Calcitonin and the C cells: role models for the neuroendocrine system.

PMID- 1348654
TI  - The cross-leg flap: still a useful flap in children.
AB  - Reconstruction of the distal lower limb and foot is a difficult problem,
      especially where large areas of skin loss have occurred. The cross-leg flap is a
      safe and reliable alternative to free tissue transfer in paediatric lower limb
      trauma. By incorporating fascia or muscle the versatility of the flap can be
      enhanced. Our experience with the cross-leg flap in children during the last 5
      years is discussed.

PMID- 1348655
TI  - Lowest effective dose of depot neuroleptics.

PMID- 1348656
TI  - [Schizophrenia: difference between the sexes].

PMID- 1348657
TI  - Atypical affective disorder with episodic dyscontrol: a case of von Economo's
      disease (encephalitis lethargica).
AB  - The case is described of a patient with atypical affective disorder, episodic
      behavioural dyscontrol and parkinsonism resulting from presumed encephalitis
      lethargica. EEG abnormalities were found which were compatible with a post
      encephalitic state and suggestive of epileptiform complications. Poor or
      deleterious response to neuroleptics, sleep disorder, and parkinsonism are
      features that may allow recognition of this illness in a psychiatric setting.

PMID- 1348658
TI  - Psychiatric emergency services in a Canadian city: II. Clinical characteristics
      and patients' disposition.
AB  - The clinical characteristics of patients seen at the psychiatric emergency
      facilities in a Canadian city and the determinants of decisions regarding their
      treatment were investigated. A total of 544 patients who sought psychiatric
      emergency services from the three hospitals in Saskatoon during a three month
      period were studied. Cognitive disturbance, past psychiatric history, previous
      psychiatric hospitalization and diagnoses of substance use disorders, affective
      disorders, anxiety disorders and schizophrenic disorders were associated with
      psychiatric emergencies. Psychiatric diagnoses and availability of social support
      were significantly associated with disposition. The implications of these
      findings for psychiatric emergency services are discussed.

PMID- 1348660
TI  - Investigational strategies for detection and intervention in early lung cancer.
      NCI workshop. Annapolis, Maryland, April 21-24, 1991.

PMID- 1348659
TI  - Truncated fibronectin. An autologous growth-promoting substance secreted by renal
      carcinoma cells.
AB  - The human renal carcinoma cell (RCC) line ACHN proliferates in the absence of
      exogenous growth factors and secretes a 178-kilodalton growth-promoting substance
      (GPS). Complementary DNA (cDNA) was isolated that coded for polypeptides
      antigenically cross-reactive with GPS. Nucleotide sequencing of the cDNA showed
      strong homology with human fibronectin (FN). The deletion of an adenine in human
      FN codon 1482 caused a reading-frame shift that predicted early termination of
      translation after 1518 amino acid residues. Western immunoblotting human FN and
      GPS with anti-human FN antibodies showed that GPS was a truncated FN. Previous
      work found that malignant cells synthesized, bound, and deposited into the
      extracellular matrix decreased amounts of FN. Addition of this substance to
      transformed cells changed their morphology but not their rate of growth. By
      contrast, partial proteolysis of FN resulted in a prominent 180-kilodalton
      fragment that stimulated DNA synthesis. Similar to this finding, the authors
      showed that truncation of fibronectin during synthesis appeared to unmask latent
      DNA synthetic stimulating activity. Polymerase chain reaction methods using
      genomic DNA from normal kidneys and RCC and primers specific for the GPS-human FN
      gene showed two products of identical size, indicating that genomic amplification
      did not cause activation of the human FN gene in RCC to produce GPS. Restriction
      fragment length analysis demonstrated identical patterns in DNA extracted from
      both normal kidneys and RCC, suggesting that chromosomal rearrangements did not
      activate the GPS-human FN gene. This study showed that genetic changes detectable
      only by DNA sequencing can explain the activation of the normal human FN gene to
      produce GPS, a product important for autologous growth stimulation of RCC.

PMID- 1348661
TI  - Overview: NCI Workshop on Investigational Strategies for Detection and
      Intervention in Early Lung Cancer.

PMID- 1348662
TI  - Determination of biomarkers for intermediate end points in chemoprevention
      trials.
AB  - Renewed interest is being directed toward chemoprevention as a means of reducing
      cancer mortality. To overcome the inherent problems associated with using cancer
      development as a study end point, there has recently been a great surge of
      interest in defining the biomarkers associated with specific stages of the
      carcinogenic process as intermediate end points. We have detailed the evidence
      supporting the concept of field cancerization, a concept of general importance
      that is probably applicable to carcinogenesis and chemoprevention at many organ
      sites in humans, and presented results of tests of the potentially useful
      biomarkers proliferating cell nuclear antigen and blood group antigen. Because
      microassay techniques are more readily applicable to small biopsy samples,
      further expansion of these studies and exploration of panels of additional
      biomarkers are expected to generate exciting results in the field of
      chemoprevention.

PMID- 1348664
TI  - Half-life of exogenous growth hormone following suppression of endogenous growth
      hormone secretion with somatostatin in type I (insulin-dependent) diabetes
      mellitus.
AB  - OBJECTIVE: To estimate the half-life of growth hormone in young adult patients
      with type I (insulin-dependent) diabetes mellitus following bolus injection and
      prolonged exposure for the purpose of deconvolution analysis of plasma growth
      hormone profiles to determine growth hormone secretory rates. DESIGN: In the
      bolus study, an intravenous bolus injection of 100 mU of biosynthetic human
      growth hormone was given while endogenous growth hormone was suppressed by a
      continuous infusion of somatostatin under three different glucose clamp
      conditions: normoglycaemia (5 mmol/l) with normoinsulinaemia (65 pmol/l);
      hyperglycaemia (12 mmol/l) with normoinsulinaemia; and normoglycaemia with
      hyperinsulinaemia (360 pmol/l). In the infusion study, the effect of prolonged
      and repeated growth hormone exposure upon the growth hormone half-life was
      estimated. Three pulses of 60 minutes growth hormone infusion (6 mU/kg/pulse) two
      hours apart under euglycaemic somatostatin suppression were applied. PATIENTS:
      Six young adult patients with type I (insulin-dependent) diabetes mellitus were
      studied in both the bolus and the infusion study. RESULTS: Mean GH half-lives by
      mono-exponential analysis were not significantly different remaining unaltered by
      the short-term metabolic changes of hyperglycaemia and hyperinsulinaemia. Data
      were therefore pooled yielding an overall mean GH half-life of 13.6 minutes
      (range 11.9-19.4). Applying a bi-exponential model mean GH half-lives were 3.1
      minutes (range 2.5-5.9) for the rapid phase of distribution of the hormone and
      13.8 minutes (range 9.6-16.9) for the decay of GH from the circulation. The GH
      half-life during the infusions studies did not vary with repeated exposure but
      was significantly longer (mean half-life of 25.7 minutes; range 19.4-37.1) than
      during the bolus studies (P less than 0.001). CONCLUSIONS: The half-life of
      exogenous r-hGH is not affected by glucose or insulin concentrations but
      increases after prolonged GH exposure in young adults with type I (insulin
      dependent) diabetes mellitus.

PMID- 1348663
TI  - Naproxen premedication reduces postoperative tubal ligation pain.
AB  - This study evaluated the effectiveness of naproxen sodium oral premedication in
      reducing postoperative pain, analgesic requirements and day surgery length of
      stay in patients undergoing outpatient laparoscopic tubal ligations. We undertook
      a randomized, double-blind clinical trial on ASA I and ASA II patients undergoing
      outpatient laparoscopic tubal ligations. The treatment group received two
      capsules containing naproxen sodium, 275 mg each, and the control group received
      two identical capsules containing placebo. Postoperative visual analogue pain
      scores, analgesic requirements, side-effects and length of day surgery stay were
      studied. Forty-four patients completed the study with 21 patients in the naproxen
      group and 23 in the placebo group. There was a statistically significant
      difference between groups in terms of pain score (naproxen group 0.9 +/- 0.2 vs
      placebo group 3.5 +/- 0.6); patients requiring postoperative opioids (naproxen
      group 0% vs placebo group 34.8%); and time spent in the day surgery unit
      (naproxen group 168 +/- 13 min vs placebo group 188 +/- 15 min). There was no
      difference in the incidence of nausea and vomiting. Only one person developed a
      side-effect from the naproxen sodium which was minor gastric discomfort. This
      study shows that naproxen decreased the postoperative tubal ligation pain with
      less subsequent postoperative analgesic requirements, less time to street fitness
      and no increase in analgesic side-effects. We recommend the use of this
      premedication in outpatient laparoscopic tubal ligations.

PMID- 1348665
TI  - Carrier detection in X-linked ocular albinism of the Nettleship-Falls type by DNA
      analysis.
AB  - X-linked ocular albinism (XOA) is characterized by anomalies of the eyes and
      hypopigmentation or absence of pigment in skin, hair and eyes due to a hereditary
      inborn error of metabolism affecting the pigment cells. The gene of XOA of the
      Nettleship-Falls type (OA1) has been mapped to Xp22.3, and several closely linked
      RFLP loci have been identified. Linkage analysis and deletion mapping have
      established the marker gene order Xpter-STS-DX237-(OA1,DXS143,DXS85)-DXS1 6-DXS43
      Xcen. Although the position of OA1 has yet not been fully resolved, we report on
      the first carrier detections in OXA of the Nettleship-Falls type by DNA analysis
      using markers which unquestionably flank OA1.

PMID- 1348666
TI  - Influence of apolipoprotein B signal peptide insertion/deletion polymorphism on
      serum lipids and apolipoproteins in a Chinese population.
AB  - Insertion/deletion polymorphism of the apo B gene encoding signal peptide and its
      influence on serum lipids and apolipoproteins was studied in 269 Chinese of both
      sexes in Singapore. The frequency of the Del allele was found to be 0.20, which
      is significantly lower than that in Caucasians (France) (0.34). The distribution
      of genotypes of ins/del polymorphism was at Hardy-Weinberg equilibrium in this
      population. There was an excess of individuals with the deletion allele in
      hypercholesterolemic subjects compared to those with normal cholesterol levels (P
      less than 0.05). All the lipid and apolipoprotein values were regressed for age,
      sex and BMI by multiple regression analysis. Individuals with one or two del
      alleles had significantly higher levels of serum total cholesterol (248.8 +/-
      13.0 and 255.4 +/- 20.4 mg/dl, respectively) compared to those in individuals
      with only the Ins allele (218.4 +/- 7.8 mg/dl) (P less than 0.05). Serum LDL
      cholesterol level was also significantly higher in individuals with del allele
      (173.4 +/- 11.7 mg/dl) compared to that in those without the del allele (141.1 +/
      7.4 mg/dl) (P = 0.02). The percentages of sample variance of different lipid
      traits explained by apo B signal peptide polymorphism were estimated by analysis
      of variance (ANOVA) with sex, age and BMI as covariates. 2.3% of variability of
      serum total cholesterol (F = 3.27, P = 0.040) and 2.8% of LDL cholesterol (F =
      3.87, P = 0.023) could be explained by the ins/del polymorphism of the apo B
      signal peptide gene.

PMID- 1348667
TI  - Differential expression of lymphocyte function-associated antigen (LFA-1) on
      peripheral blood leucocytes from individuals with Down's syndrome.
AB  - We analysed the expression of lymphocyte function-associated antigen LFA-1 on the
      cell surface of peripheral blood lymphocytes, monocytes and granulocytes from 20
      children with Down's syndrome. No differences in LFA-1 expression was found
      within monocytes or granulocytes from either normal or Down's syndrome children;
      however, a clear-cut difference was observed on lymphoid cells. Both normal and
      Down's syndrome lymphocytes displayed a bimodal pattern of LFA-1 staining by flow
      cytometry, with a predominance of cells with low expression in normal population,
      and an increased proportion of lymphocytes with high level of LFA-1 expression in
      Down's syndrome children. This difference correlates well with the abnormal
      proportion of T cell subsets and inversion of CD4/CD8 observed in a majority of
      our cases, and therefore, it could merely reflect the increase of certain T cell
      subsets normally expressing higher number of LFA-1 molecules. Taken together, our
      results do not support an abnormally increased expression of leucocytes integrins
      in trisomy 21 cells, and raise some doubt about the suggested role of the
      abnormal cellular expression of LFA-1 in the pathogensis of secondary
      immunodeficiency associated to Down's syndrome.

PMID- 1348668
TI  - Cytomegalovirus (CMV) infection, CD4+ lymphocyte counts and the development of
      AIDS in HIV-1-infected haemophiliac patients.
AB  - After a maximum of 11 years (median 8.3 years) from the time of HIV
      seroconversion, 25 out of 59 (42%) of CMV-seropositive haemophiliacs had
      progressed to AIDS, as opposed to eight out of 50 (16%) CMV seronegatives. The
      age-adjusted relative risk for AIDS among CMV seropositives was 2.4 (P = 0.03).
      In order to determine how this adverse effect is mediated, the mean rate of
      decline in serial CD4+ lymphocyte counts was studied. CD4+ lymphocyte counts
      tended to decline more rapidly in CMV seropositives than in seronegatives (-0.087
      x 10(9)/l per annum versus -0.082 x 10(9)/l per annum), but this difference did
      not reach statistical significance. The average CD4+ lymphocyte count at the time
      of HIV seroconversion was estimated to be similar in CMV seropositives and
      negatives, because in HIV-1-negative haemophiliacs the CD4+ counts were virtually
      identical, after adjustment for age (0.94 x 10(9)/l and 0.97 x 10(9)/l,
      respectively). The median CD4+ cell count at which AIDS developed was higher in
      the CMV-seropositive group (0.07 x 10(9)/l) than in the seronegative group (0.04
      x 10(9)/l), but this difference did not reach statistical significance. We
      conclude from these findings that the adverse effect of CMV is not wholly
      mediated via a more rapid loss of CD4+ cells. We discuss other processes that may
      be mediated by CMV, such as a functional deficiency of residual CD4+ cells, or
      dissemination of HIV in other organs, which may be important in determining the
      earlier onset of AIDS among CMV-seropositive subjects.

PMID- 1348670
TI  - Combination therapy with nicardipine and beta-adrenergic blockade for angina
      pectoris.
AB  - Nicardipine a second-generation dihidropyridine calcium antagonist, has been
      approved in oral formulation for use in the United States, and is under review
      for parenteral use. Nicardipine is the most vascular-selective agent of this
      class currently approved and should, on theoretical grounds, be ideal for
      combination therapy with beta-adrenergic blocking agents. Studies have shown that
      the combination of nicardipine and beta-blocking agents offers additional
      efficacy over monotherapy with either agent alone. The hemodynamic profile of
      combination therapy appears to be especially favorable in patients with
      diminished left ventricular function needing therapy with agents of both classes.
      Adverse effects are few and may be improved compared with other agents of the
      dihidropyridine class.

PMID- 1348669
TI  - "False positive" perinuclear and cytoplasmic anti-neutrophil cytoplasmic antibody
      results leading to misdiagnosis of Wegener's granulomatosis and/or microscopic
      polyarteritis.
AB  - The antineutrophil cytoplasmic antibody (ANCA) test has been shown to be
      important in helping to confirm the diagnosis and following the clinical course
      of microscopic polyarteritis and Wegener's granulomatosis. So called "false
      positive" test results have been reported, but usually in patients without any
      clinical evidence of these diseases, and the "false positive" result ignored. I
      wish to report 4 cases, in which a diagnosis of microscopic
      polyarteritis/Wegener's granulomatosis was considered as part of the differential
      diagnosis based on the clinical findings. The ANCA test was positive for
      cytoplasmic staining in 2 cases and perinuclear in 2 others. The combination of a
      positive ANCA result and the clinical possibility of Wegener's granulomatosis
      and/or microscopic polyarteritis resulted in the prescription of
      immunosuppressive treatment, with the consequent mortality of one patient and
      significant morbidity in two of the other cases.

PMID- 1348671
TI  - Intracellular pH regulation in intestinal and renal epithelial cells.

PMID- 1348672
TI  - Periodicities and transient shifts in anuran (Xenopus laevis, Rana clamitans)
      oxygen consumption revealed with flow-through respirometry.
AB  - 1. A custom-designed, computer-controlled, flow-through respirometry system was
      used to monitor oxygen consumption in aquatic anurans: Xenopus laevis metamorphs
      and larval Rana clamitans. 2. There was no evidence that animals were stressed in
      the flow-through respirometer; oxygen consumption rates in static vs open mode
      fell within the same range and animals were quiescent in the chambers. 3. Diurnal
      periodicity was pronounced in X. laevis: both mean rates and variability of
      oxygen consumption were higher during scotophase, although individual differences
      in the timing of peaks were pronounced. 4. A transient peak in metabolism
      following introduction of ethanol, with subsequent recovery, was monitored for X.
      laevis.

PMID- 1348673
TI  - Effects of acid Ca2+ Ringer on passive electrical properties and intracellular
      ion activities in leech Retzius neuron.
AB  - 1. A significant drop in effective input resistance of the free membrane and an
      increase in effective coupling resistance in acid Ca2+ Ringer (complete
      replacement of Na+ with Ca2+, pH 4) compared to control medium has been obtained
      in leech Retzius neurons. 2. In neutral Ca2+ Ringer (pH 7.2), effective input
      resistance increased while effective coupling resistance did not change. In acid
      sodium, leech Ringer (pH 4) effective input resistance increased while coupling
      resistance decreased. 3. Ten millimolar manganese and 10 mmol tetraethylammonium
      did not block conductance changes obtained in acid Ca2+ Ringer. 4. Intracellular
      activity of Na+ decreased, cellular activity of Cl- increased and intracellular
      K+ activity was unchanged in both acid and neutral Ca2+ Ringer. 5. The main
      difference was intracellular acidification in acid Ca2+ Ringer while
      intracellular pH was unchanged in neutral Ca2+ Ringer. 6. We discuss the
      possibility that in acid Ca2+ Ringer, intracellular acidification in leech
      neurons may be responsible for accompanying conductive changes.

PMID- 1348674
TI  - Granule containing cells in the crayfish third abdominal ganglion.
AB  - 1. Four of the 850 neuron cell bodies of the crayfish third abdominal ganglion
      contain large dense secretory granules. 2. The processes of these cells form a
      neurohemal organ in the dorsal perineurium/neurilemma in the ganglion. 3. None of
      the immunocytochemically identified peptides accounts for the observed
      distribution of granules.

PMID- 1348675
TI  - Endogenous, photoperiodic and hormonal control of the body weight rhythm in the
      female European hamster, Cricetus cricetus.
AB  - 1. Body weight and hibernation rhythms were followed on normal and castrated
      female European hamsters raised in different conditions of photoperiod and
      ambient temperature. 2. In the normal females, the photoperiod was more effective
      than the ambient temperature regarding the control of the body weight rhythm. 3.
      In the castrated females, testosterone was more effective than oestradiol in
      suppressing both body weight and hibernation rhythms. 4. In short photoperiod
      conditions, the existence of endogenous rhythmicity depends upon prior
      photoperiodic exposure of the animals.

PMID- 1348676
TI  - The detection of intracellular bluetongue virus particles within ovine
      erythrocytes.
AB  - 1. We report here a simplified method for detecting viruses and other antigenic
      agents in red blood cells (RBCs). Using a nonionic detergent to prepare
      cytoskeletons, the interior of RBCs can be scanned rapidly using immunoelectron
      microscopy. 2. In this study, RBCs from bluetongue (BLU) virus-infected sheep
      were adsorbed directly onto Formvar-coated, gold electron microscope grids. 3.
      Cytoskeletons were prepared and then probed using a monoclonal antibody to VP 7,
      a structural BLU-virus protein and Protein-A gold. 4. Of the ca 32,000 RBCs that
      were examined from BLU virus-infected sheep, 34 (0.106%) contained labelled BLU
      virus particles. 5. No labelled particles were observed in any of ca 8000 RBCs
      taken prior to BLU virus inoculation of sheep. 6. If the antigenic BLU virus
      particles (which may be viral cores) are in fact infectious, this method of
      sequestration of virus within RBCs could contribute to the prolonged viremia
      typical of this arboviral disease, which is known to occur concurrently with
      circulating neutralizing antibody.

PMID- 1348678
TI  - Sustained potential shift responses and their relationship to the ECG response
      during arousal in the goldfish (Carassius auratus).
AB  - 1. Goldfish, when presented with a 10 sec light-on stimulus against a background
      of 2 hr of sensory restriction, exhibited sustained potential shift (SPS)
      activity, of differing polarity, at each of four surface recording sites, on the
      medulla, cerebellum, optic tectum and telencephalon. 2. Principle components
      analysis (PCA) indicated that SPS responses from each region comprised
      superimposed early and late waveforms. At the cerebellar, tectal and
      telencephalic surfaces, neuronal activity appeared to contribute strongly to the
      early (less than 2 sec) SPS waveform. 3. While, in response to repeated stimulus
      presentations, habituation was apparent in the early SPS waveforms recorded from
      the medulla, cerebellum and telencephalon, an increase in negativity occurred in
      late SPS waveforms throughout the brain. 4. The tectal SPS response was directly
      proportional to the telencephalic SPS response both in terms of average SPS
      amplitudes following the first presentation of the light-on stimulus and in terms
      of their increasing negativity in response to stimulus repetition. 5. The
      increasing negativity of the telencephalic SPS was also associated with the
      habituation of the ECG response over repeated trials. 6. Results are discussed
      with regard to a possible neuromodulatory role for glia.

PMID- 1348677
TI  - Prostaglandin interacts with steroid sex hormones in the regulation of intestinal
      zinc transport.
AB  - 1. The effects of prostaglandins (PGs) E1 and E2, testosterone, 17 beta-estradiol
      and indomethacin on the intestinal zinc transport rates of male and female rats
      were compared. 2. PGE1 stimulated Jms (the zinc flux rate from mucosa-to-serosa)
      of jejunal segments from male rats but inhibited Jms of those from female rats in
      Ussing chamber experiments. 3. 17 beta-Estradiol inhibited Jms of jejunal
      segments from male rats, while testosterone stimulated it in those from female
      rats. However, testosterone inhibited Jms of segments isolated from male rats and
      17 beta-estradiol that of those from female rats, while in segments from
      ovariectomized rats, both of these steroid hormones stimulated Jms. 4. When PGE2
      was added to an indomethacin containing medium, Jms significantly increased
      whereas Jsm (the zinc flux rate from serosa-to-mucosa) decreased further.

PMID- 1348680
TI  - The effect of dehydration on brain temperature regulation in Japanese quail
      (Coturnix coturnix japonica).
AB  - 1. The effect of dehydration and heat exposure on body and brain temperature was
      studied in quail exposed to increasing ambient temperatures within the range of
      25-40 degrees C. 2. The body-to-brain temperature difference was not affected by
      increasing ambient temperature or hydration state. A mean body-to-brain
      temperature difference of 0.96 +/- 0.64 degrees C and 0.85 +/- 0.65 degrees C was
      found in normally hydrated and dehydrated quail, respectively. 3. The slope of
      the relation between brain temperature to body temperature (0.77) was
      significantly lower than 1.0 (P less than 0.001), when the results of the two
      hydration states were pooled. This indicates increased brain cooling with
      increased body temperature. 4. Body and brain temperatures of water-deprived
      quail were significantly higher (P less than 0.05) than those of hydrated birds
      during exposure to ambient temperatures of 35 and 40 degrees C. 5. Respiration
      frequency increased during exposure to 35 (four birds) and 40 degrees C (six
      birds) in the normally hydrated quail, while in the dehydrated quail, respiration
      frequency increased only in three birds during exposure to 35 degrees C, and four
      birds during exposure to 40 degrees C, the frequencies were lower during
      dehydration. 6. Plasma osmolality and chloride concentration were significantly
      higher in the dehydrated quail (P less than 0.05). 7. The present findings show
      that dehydration and heat exposure resulted in a relative hyperthermy, and thus
      implying a reduced evaporative cooling. The quail appears to be well adapted to
      dehydrating conditions.

PMID- 1348679
TI  - Potassium transport in lamprey (Lampetra fluviatilis) erythrocytes: evidence for
      K+ channels.
AB  - 1. Unidirectional K+ (86Rb) influx in lamprey red blood cells was studied under
      different conditions. 2. The influx of 86Rb was markedly inhibited by 1 mM Ba2+
      when cells were incubated in saline containing 4 mM K+. In K(+)-free media, the
      influx rate constant of 86Rb was lower, and 1 mM Ba2+ had no blocking effect. 3.
      Treatment of the red cells with 0.1 mM ouabain in the absence of external K+
      resulted in the appearance of the component of 86Rb influx inhibited by 1 mM
      Ba2+, quinine, TEA or amiloride. 4. Similar results were obtained in red cells
      incubated in Na(+)-free media MgCl2-sucrose. 5. The results obtained provide
      evidence for the existence of K+ channels in the red cell membrane of the
      lamprey. Under physiological conditions (in the presence of 4 mM K+) the total
      rate constant for the 86Rb influx in erythrocytes was about 1.9/hr, including
      ouabain-sensitive (0.6/hr), Ba(2+)-sensitive (1.1/hr) and residual (0.2/hr)
      components.

PMID- 1348681
TI  - Mitochondrial adaptations to chronic muscle use: effect of iron deficiency.
AB  - 1. The effects of chronic muscle use on mitochondrial structure, enzymes and gene
      expression is reviewed. The role of iron deficiency in modulating this adaptation
      is discussed. 2. Chronic muscle use and disuse alter mitochondrial composition
      and affect mitochondrial subpopulations differentially. This has implications for
      an understanding of organelle assembly. 3. Iron deficiency decreases
      mitochondrial functional mass within muscle by reducing the level of heme and non
      heme iron-containing components. This alters the metabolic response during
      exercise and results in a reduced endurance performance. 4. Both iron deficiency
      and chronic muscle use represent contrasting experimental models for the study of
      mitochondrial function and biogenesis.

PMID- 1348682
TI  - Diet fatty acid composition, age and rat jejunal microvillus enzyme activities.
AB  - 1. Lactase, sucrase, maltase, trehalase and alkaline phosphatase activities of
      rat proximal jejunum were measured in 3, 6, 9, 12, 18 and 24-month-old rats fed
      with diets differing in their fatty acid composition. 2. A drop of 47-53% of the
      specific enzyme activity was observed with disaccharidases against a decrease of
      71% for alkaline phosphatase in the 24-month-old rats compared to the 3-month-old
      rats. 3. Changes in dietary fatty acid composition, either in the saturated or
      monounsaturated ratio, or in the polyunsaturated fatty acid composition, did not
      significantly interfere with this aging effect.

PMID- 1348683
TI  - Effects of various fat sources on growth and hepatic mitochondrial function in
      mice.
AB  - 1. Five parameters with biophysical meaning for Parks' feeding and growth
      equations showed that mice fed diets containing hydrogenated beef tallow or beef
      tallow had lower mature body weight than soybean oil, linseed oil or fish oil-fed
      groups, and that mice fed hydrogenated beef tallow or fish oil diets had a lower
      feed efficiency factor than beef tallow, soybean oil or linseed oil-fed groups.
      2. Mice fed the diet containing soybean oil or linseed oil had higher carcass fat
      as a per cent of body weight, significantly different from mice fed hydrogenated
      beef tallow, which exhibited the lowest carcass fat. 3. The respiratory rate of
      state 3 and the rate of ATP synthesis of liver mitochondria isolated were highest
      in the group fed the diet containing soybean oil.

PMID- 1348684
TI  - Influence of clenbuterol on the protein digestibility and on nitrogen balance in
      rats.
AB  - 1. The influences of a beta-agonist, clenbuterol, on the fecal and urinary
      nitrogen excretion, the protein digestibility and the nitrogen balance and
      retention in female Wistar rats of three different weights (70, 150 and 200 g)
      have been studied. 2. The addition of clenbuterol to the diet did not alter the
      fecal nitrogen excretion, nor did it change the digestibility coefficient of the
      protein, irrespective of the age/weight of the animals and the amount of the beta
      agonist used. 3. Clenbuterol decreased the urinary nitrogen excretion, especially
      in older/heavier animals and fed diets with the same dose of the agonist. 4.
      Nitrogen balance and retention, which, as expected, decrease as the age/weight of
      the animals decreases, increased significantly with the use of clenbuterol,
      especially in older/heavier animals. 5. From the results of this study, it can be
      concluded that, for the range of weight studied, the effect of this beta-agonist
      does not show on the absorption of proteins at the digestive level; at a
      metabolic level, however, it does affect the nitrogen retention although, again,
      to a greater extent in older/heavier animals.

PMID- 1348685
TI  - Social stress and atherosclerosis in roosters.
AB  - 1. Socially stressed roosters fed either plain mash or an atherogenic diet had a
      greater incidence and severity of aortic atherogenesis than similarly fed non
      stressed birds. 2. Results demonstrated a significant atherogenic effect of
      stress in chickens even in the absence of hyperlipidaemia. 3. Lack of appreciable
      differences in plasma lipids between stressed and non-stressed birds suggested
      that the atherogenic effects of stress may be attributable to neuroendocrine
      responses. 4. Levels of HDLc of plain mash groups were significantly higher than
      in the atherogenic fed groups. 5. Haemodynamic data showed no treatment-related
      differences.

PMID- 1348686
TI  - Influence of dietary protein concentrations or of duodenal amino acid infusion on
      cholecystokinin release in goats.
AB  - 1. Whether dietary protein levels or duodenal infusion of amino acids alters the
      release of cholecystokinin (CCK) in blood plasma of goats was investigated in
      three experiments. The CCK determination was done by radioimmunoassay with
      specific CCK-8 antibody. The male adult Shiba goat, a miniature Japanese native
      goat, was used. 2. In Experiment 1, four goats were offered a diet containing
      4.94 g crude protein (CP)/kg BW0.75 for the first 7 days. They were then given a
      diet containing 5.86 g CP/kg BW0.75 for 7 days and thereafter 6.79 g CP/kg BW0.75
      for the following 7 days. On the last day of each experimental period, blood
      samples were taken from the jugular vein at zero (before feeding), 30, 60, 120,
      240 or 360 min after the feeding of the diet. Plasma CCK levels were not affected
      by dietary protein levels and time after feeding. 3. Influence of phenylalanine
      or tryptophan (2 mmol/20 ml) infusion into the duodenum was investigated by a 3 x
      3 latin square in Experiment 2. Plasma CCK level was determined at 15 min
      intervals for 1 hr. Both phenylalanine and tryptophan gradually enhanced plasma
      CCK concentrations with time after infusion. 4. Branched-chain amino acids such
      as leucine and isoleucine were supplemented intraduodenally in Experiment 3 as in
      Experiment 2. No significant change in plasma CCK levels was observed.

PMID- 1348687
TI  - Familial increase in plasma glutamic acid in epilepsy.
AB  - Plasma levels of glutamic acid and leukocyte glutamate dehydrogenase (GDH)
      activity were determined in patients with primary generalized epilepsy, patients
      with partial epilepsy and in the first-degree relatives of these subjects. The
      results show a significant increase in plasma glutamic acid in both groups of
      patients and their relatives compared to non-epileptic controls. The leukocyte
      GDH activity in the patients and the relatives was not different from controls.
      The data support a genetic basis for plasma glutamic acid increase in both
      primary generalized and partial epilepsy and are compatible with the
      multifactorial mode of inheritance of these disorders. This is the first study
      showing a familial plasma glutamic acid increase in epilepsy in a Japanese
      population.

PMID- 1348689
TI  - Expression of Hox-4 genes in the chick wing links pattern formation to the
      epithelial-mesenchymal interactions that mediate growth.
AB  - The relationship between the expression of Hox-4 genes in the mesenchyme and the
      apical ectodermal ridge was investigated in both normal chick wing buds and wing
      buds treated with retinoic acid. Two conclusions emerge. One is that the
      activation of Hox-4 domains and the elaboration of Hox-4 gene expression patterns
      involve cooperation with a signal from the apical ridge. The second is that the
      domains of expression of 5'-located members of the complex correlate with the
      maintenance of the thickened ridge which is required for subsequent bud
      outgrowth.

PMID- 1348688
TI  - Structural complexity and evolutionary conservation of the Drosophila homeotic
      gene proboscipedia.
AB  - Mutations of the homeotic gene proboscipedia (pb) of Drosophila cause striking
      transformations of the adult mouthparts, to legs or antennae. We report here an
      analysis of the gene structure of pb. Coding sequences across a 34 kb interval
      yield, by alternative splicing, four identified mRNA forms which differ
      immediately upstream of the homeobox. As a consequence, the homeodomain is
      expected to reside in four different contexts in the predicted protein isoforms.
      Mammalian homologs of pb, human HOX-2H and murine Hox-2.8, were identified based
      on the similarities of their homeodomains (95% identity) and several other
      conserved motifs. Examination of a collection of pb mutant alleles with antisera
      directed against the N-terminal region, the center or the C-terminal region of
      the protein showed that, surprisingly, several partial loss-of-function pb
      alleles appear to generate partially functional proteins truncated at their C
      termini. This suggests that a significant portion of the protein contributes
      quantitatively to pb function, but is partially dispensable. Finally,
      evolutionary considerations suggest that pb may be one of several ancient genes
      which preceded the process yielding the modern homeotic gene complexes.

PMID- 1348690
TI  - Comparison of mouse and human HOX-4 complexes defines conserved sequences
      involved in the regulation of Hox-4.4.
AB  - We have cloned and sequenced, in both mouse and human, regions of the HOX-4
      complex which contain two Abd-B like genes, Hox-4.4 and Hox-4.5 (HOX4C and HOX4D
      in human, respectively). The high degree of conservation between the homeoprotein
      sequences extends to non-coding areas, which suggests that the mechanisms of
      regulation have been conserved. We show that the Hox-4.5/Hox-4.4 intergenic
      region can be broadly subdivided into three domains based on DNA conservation
      between rodents and primates. The presence of all these domains in association
      with sequences located 3' to the transcription termination site are required to
      mimick the spatial regulation of Hox-4.4 in transgenic mouse embryos. Several
      highly conserved short sequences located in this region were studied in gel
      retardation assays for their binding to potential regulatory factors. One such
      factor is detected in embryonal carcinoma cells but absent from other
      differentiated cell lines. This specific binding activity is down regulated upon
      retinoic acid treatment.

PMID- 1348693
TI  - Magnetic resonance: assessing the potentials. The Nijmegen MR Symposium. March 27
      28, 1992.

PMID- 1348692
TI  - Conserved immunoglobulin-like features in a family of periplasmic pilus
      chaperones in bacteria.
AB  - Detailed structural analyses revealed a family of periplasmic chaperones in Gram
      negative prokaryotes which are structurally and possibly evolutionarily related
      to the immunoglobulin superfamily and assist in the assembly of adhesive pili.
      The members of this family have similar structures consistent with the overall
      topology of an immunoglobulin fold. Seven pilus chaperone sequences from
      Escherichia coli, Haemophilus influenzae and Klebsiella pneumoniae were aligned
      and their consensus sequence was superimposed onto the known three-dimensional
      structure of PapD, a representative member of the family. The molecular details
      of the conserved and variable structural motifs in this family of periplasmic
      chaperones give important insight into their structure, function, mechanism of
      action and evolutionary relationship with the immunoglobulin superfamily.

PMID- 1348691
TI  - Human p68 kinase exhibits growth suppression in yeast and homology to the
      translational regulator GCN2.
AB  - The human p68 kinase is an interferon-regulated enzyme that inhibits protein
      synthesis when activated by double-stranded RNA. We show here that when expressed
      in Saccharomyces cerevisiae, the p68 kinase produced a growth suppressing
      phenotype resulting from an inhibition of polypeptide chain initiation consistent
      with functional protein kinase activity. This slow growth phenotype was reverted
      in yeast by two different mechanisms: expression of the p68 kinase N-terminus,
      shown to bind double-stranded RNA in vitro and expression of a mutant form of the
      alpha-subunit of yeast initiation factor 2, altered at a single phosphorylatable
      site. These results provide the first direct in vivo evidence that the p68 kinase
      interacts with the alpha-subunit of eukaryotic initiation factor 2. Sequence
      similarity with a yeast translational regulator, GCN2, further suggests that this
      enzyme may be a functional homolog in higher eukaryotes, where its normal
      function is to regulate protein synthesis through initiation factor 2
      phosphorylation.

PMID- 1348694
TI  - Annexin I and involucrin are cross-linked by particulate transglutaminase into
      the cornified cell envelope of squamous cell carcinoma Y1.
AB  - The squamous cell carcinoma line, SqCC/Y1, like natural squamous epithelia, forms
      a cornified cell envelope during differentiation which can be directly correlated
      with an increase in particulate transglutaminase activity. When transglutaminase
      is activated in these cells by calcium ionophore X-537A, annexin I and involucrin
      become incorporated into the cornified cell envelope and cannot be extracted with
      solutions containing sodium dodecyl sulfate (SDS) and beta-mercaptoethanol. This
      effect is specific for annexin I; thus, the amounts of annexins II and IV that
      were extractable from cells by SDS and beta-mercaptoethanol did not change
      following treatment with ionophore X-537A. Annexin I could be cross-linked in
      vitro to itself and to other endogenous proteins by transglutaminase extracted
      from the particulate fraction of SqCC/Y1 cells. Immunofluorescence studies showed
      that cross-linked annexin I and involucrin form an envelope-like structure in
      SqCC/Y1 cells during differentiation that cannot be extracted by EGTA and Triton
      X-100. The amount of staining of this envelope structure corresponded directly to
      the particulate transglutaminase activity of these cells. Annexin I monoclonal
      and polyclonal antibodies were shown to bind to purified cornified cell envelopes
      from SqCC/Y1. These studies suggest that particulate transglutaminase regulates a
      function of annexin I during the differentiation of SqCC/Y1 cells by covalently
      cross-linking this protein into the cornified cell envelope.

PMID- 1348696
TI  - Regulation of metabolisms. Proceedings of the Metabolism Meeting of the
      Association Francaise de Nutrition. Theix, 26-27 June 1990.

PMID- 1348697
TI  - Acquired gynetresia in eastern Nigeria.
AB  - A retrospective analysis of 78 patients who presented with acquired vaginal
      stenosis between January 1980 and December 1989 at the University of Nigeria
      Teaching Hospital Enugu was carried out. Ritual circumcision was a leading cause
      of this condition, followed by birth injuries and postoperative injuries. Urinary
      symptoms such as dysuria and urinary retention, as well as coital difficulty
      presenting as dyspareunia and apareunia featured prominently amongst the
      patients. The modified Fenton's operation was used in treating a majority of the
      patients, with good results. Occasionally more extensive surgery such as the
      McIndoe operation was used when the lesion was more severe. Recurrence rate was
      low and 11 women became pregnant during the period of follow up. The problem is
      of public health dimensions, and community based education to eliminate the
      etiological factors is recommended.

PMID- 1348695
TI  - Staurosporine induces a neuronal phenotype in SH-SY5Y human neuroblastoma cells
      that resembles that induced by the phorbol ester 12-O-tetradecanoyl phorbol-13
      acetate (TPA).
AB  - Treatment of SH-SY5Y human neuroblastoma cells with the protein kinase inhibitor
      staurosporine, induced both morphological and functional differentiation in these
      cells. The effects of staurosporine were comparable to those induced by the
      protein kinase C (PKC) activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA),
      with respect to induction of neuronal differentiation, i.e. neurite outgrowth,
      inhibition of DNA synthesis, induction and down-regulation of c-myc protein
      expression, induction of mRNA for both neuropeptide Y (NPY) and growth associated
      protein 43 (GAP-43) and stimulation of tyrosine hydroxylase expression.
      Staurosporine failed to translocate PKC to the membrane fraction or to stimulate
      phosphorylation of the endogenous PKC substrate M(r) 80,000 (p80). Instead,
      staurosporine inhibited TPA-induced phosphorylation of p80.

PMID- 1348698
TI  - CA-125 in menstrual discharge in patients with chronic pelvic pain.
AB  - CA-125 levels in menstrual discharge were determined in 55 patients with chronic
      pelvic pain to evaluate whether this test would be useful in differentiating
      between pelvic pain due to endometriosis and other causes. Of the 28 women with
      endometriosis, 25 (89%) had CA-125 concentration greater than or equal to 72,000
      units/ml. The frequencies of elevated levels in Stage I, Stage II and Stages
      III/IV were 85.7, 85.7 and 92.8%, respectively. When used for the detection of
      endometriosis, the test had a sensitivity of 89.3% and a specificity of 96.3%.
      These results suggest that CA-125 in menstrual discharge may be helpful in the
      evaluation of women with chronic pelvic pain.

PMID- 1348699
TI  - Pelvic tuberculosis.
AB  - Pelvic tuberculosis was diagnosed in 72 patients analyzed during the years 1979
      1989. Twenty-nine percent of the patients were over 40 years of age. The most
      common complaints were infertility (47.2%), abdominal or pelvic pain (32%) and
      abnormal uterine bleeding (11%). Only 2 patients had past or family history of
      pulmonary tuberculosis. The physical examination was normal in 31.6% of the
      patients. The chest X-ray was normal in 81% of the patients. Blocked tubes were
      present in 32 of 34 patients who had hysterosalpingograms. Even if the diagnosis
      can be made from a histopathologic examination, hysterosalpingography is also a
      very useful aid in establishing a diagnosis. The most common site of infection
      was the tubes. Reconstructive surgery was performed in nine patients. Only one
      pregnancy was found in the present study without any medical or surgical
      treatment of pelvic tuberculosis. In one patient with habitual abortion as a
      cause endometrial tuberculosis was also found.

PMID- 1348700
TI  - Hysteroscopy in the diagnosis of suspected interstitial pregnancy.
AB  - Three cases are reported in which interstitial pregnancy was suspected on
      ultrasound scan. The first was managed by scans and laparoscopy, but resulted in
      rupture of the uterus and hysterectomy at 20 weeks. In the following cases
      hysteroscopy was used to refute the diagnosis in one patient and confirm it in
      another within the first trimester. A case is made for the use of hysteroscopy in
      the assessment of patients with suspected interstitial pregnancy.

PMID- 1348701
TI  - Tuberculous vesico-vaginal fistula.
AB  - A 32-year-old female with a past history of pulmonary tuberculosis presenting
      with dribbling of urine per vaginam had a small fistulous opening in the anterior
      vaginal wall. Chest X-ray showed active tuberculosis. Right hydronephrosis and
      hydroureter with autonephrectomy of left kidney and vesico-vaginal fistula were
      demonstrated on intravenous urography. On cystoscopy, the bladder was contracted
      with two small fistulous openings. Cecocystoplasty and repair of fistulae were
      successfully done. Histology of bladder wall showed tuberculous cystitis.

PMID- 1348702
TI  - Total sodium-potassium ATPase activity on erythrocyte ghosts in normal pregnancy.

PMID- 1348703
TI  - Stress in the practice of obstetrics and gynecology.

PMID- 1348704
TI  - Ethical issues in surrogate motherhood.

PMID- 1348705
TI  - Female circumcision. Female genital mutilation.

PMID- 1348706
TI  - Maternal morbidity in developing countries: a review and comments.
AB  - The incidence and prevalence of postpartum maternal morbidity in developing
      countries are poorly understood. Methodologic problems, such as lack of standard
      definitions, misclassification of illnesses, use of nonrepresentative samples,
      and inadequate validation for self-reported data, tend to compromise existing
      studies. Available data suggest that serious acute illnesses are common,
      affecting as many as 20% of mothers who deliver in hospitals in some areas.
      Providing good antenatal and family planning services should significantly reduce
      acute and chronic sequelae after parturition.

PMID- 1348707
TI  - Level and causes of maternal mortality in Guinea (West Africa).
AB  - In order to evaluate the level of maternal mortality at Conakry, capital of
      Guinea (West Africa), a descriptive epidemiological study was made of all
      maternal deaths occurring between July 1st, 1989 and June 30th, 1990. To ensure
      that cases of maternal death were recorded as exhaustively as possible, we
      conducted this study over 1 year in municipal and hospital maternity units, and 3
      months in the urban community. One hundred thirty-nine maternal deaths were
      registered, representing an annual maternal mortality rate of 559/100,000 live
      births. The main causes of maternal death were abortion, complications linked
      with hypertension, and postpartum bleeding.

PMID- 1348708
TI  - Small for gestational age twins: a retrospective analysis of clinical and acid
      base status immediately after delivery.
AB  - In a retrospective study on 86 twins born between 1971 and 1990, the clinical and
      acidity status of small for gestational age twins in cases of uncomplicated labor
      was analysed and compared with the status of appropriate for gestational age
      twins. No difference was observed in Apgar score and umbilical blood pH between
      growth retarded and normal twins. The single fact of growth retardation without
      other factors of risk during labor has no influence on clinical status of small
      for gestational age twins.

PMID- 1348709
TI  - Usefulness of the urinary microalbumin/creatinine ratio in predicting pregnancy
      induced hypertension.
AB  - In 199 normotensive pregnant women at 20 and 30 weeks of gestation, a fasting
      urinary albumin/creatinine ratio (FU Alb/Cr) was evaluated to predict pregnancy
      induced hypertension (PIH). FU Alb/Cr in patients destined to develop PIH was
      significantly high compared to that in normotensive women. When FU Alb/Cr of more
      than 16 was considered to represent a positive test result, the negative
      predictive value was 94% and 96%, respectively. FU Alb/Cr is a useful screening
      tool for PIH.

PMID- 1348710
TI  - Metabolic actions of insulin-like growth factor II in cultured adult rat
      hepatocytes are not mediated through the insulin-like growth factor II receptor.
AB  - Short- and long-term regulation of hepatic carbohydrate metabolism by insulin
      like growth factor II was studied in primary cultures of adult rat hepatocytes
      and compared to the metabolic potency of insulin. Insulin-like growth factor II
      stimulated glycogen synthesis from [14C]glucose, uptake of [3H]aminoisobutyric
      acid and [14C]lactate formation from [14C]glucose up to three-fold. Basal
      glycogenolysis was inhibited to about 10%, and glucagon-activated glycogenolysis
      was blocked completely. The enzymatic activity of glucokinase and pyruvate kinase
      was induced two-fold, the glucagon-dependent induction of phosphoenolpyruvate
      carboxykinase was antagonized. Compared to insulin, half-maximal responses
      required up to 50 times higher insulin-like growth factor II concentrations
      ranging from 10-20 nmol/l. A similar difference was observed for binding affinity
      of insulin-like growth factor II to the insulin receptor. The interaction with
      the insulin-like growth factor II/mannose 6-phosphate (IGF-II/Man-6-P) receptor
      was examined by studying 125I-insulin-like growth factor II binding and uptake of
      lysosomal enzymes. The affinity of insulin-like growth factor II to the IGF
      II/Man-6-P receptor was considerably higher than for the insulin receptor.
      Antibodies against the IGF-II/Man-6-P receptor did not affect metabolic responses
      to insulin-like growth factor II, while binding to its receptor and the receptor
      mediated endocytosis of arylsulphatase A were strongly inhibited. Thus, in adult
      rat liver insulin-like growth factor II appeared to exert metabolic actions not
      via interaction with its own receptor but through low affinity binding to hepatic
      insulin receptors.

PMID- 1348712
TI  - Different genetic backgrounds for malnutrition-related diabetes and type 1
      (insulin-dependent) diabetes mellitus in south Indians.
AB  - HLA-DRB, -DQA and -DQB genes were studied in ten South Indian malnutrition
      related diabetic patients, ten Type 1 (insulin-dependent) diabetic patients and
      45 control subjects, by TaqI restriction fragment length polymorphism analysis.
      The DR7,DQw9 haplotype was found to be frequent in patients with malnutrition
      related diabetes (p less than 0.01). The DRw17,DQw2 haplotype was overrepresented
      in the patients with Type 1 diabetes compared to control subjects (p less than
      0.05). In vitro amplification of the polymorphic second exon of DQB genes by the
      polymerase chain reaction technique was performed on DNA from 10 malnutrition
      related diabetic patients, 10 Type 1 diabetic patients and 13 control subjects,
      as they belong to a new population. Hybridization with sequence-specific
      oligonucleotide probes for DQB1 alleles showed homozygosity of aspartic acid at
      position 57 in 7 of 10 malnutrition-related diabetic patients compared to 2 of 10
      Type 1 diabetic (p less than 0.05) and 15 of 45 control subjects (p less than
      0.05). Homozygosity of non-aspartic acid at position 57 was present in 7 of 10
      Type 1 diabetic compared to 0 of 10 malnutrition-related diabetic patients (p
      less than 0.005) and 3 of 45 control subjects (p less than 0.05). This study has
      confirmed the association of DQB1 57 non-asp in South Indians with Type 1
      diabetes. In addition, our data clearly show that the genetic background of
      malnutrition-related diabetes mellitus is different from that of Type 1 diabetes.

PMID- 1348711
TI  - HLA haplotypes in type 1 (insulin-dependent) diabetes mellitus: molecular
      analysis of the HLA-DQ locus. The DIME Study Group.
AB  - In Caucasians the predisposition to Type 1 (insulin-dependent) diabetes mellitus
      has been shown to associate with HLA-DR3,DQw2 and DR4,DQw8 and with the presence
      of amino acids other than aspartic acid at position 57 on the HLA-DQ beta chain.
      In Finland the haplotype-specific absolute risk for developing Type 1 diabetes
      differs between various DR3 and DR4 positive haplotypes. The aim of our present
      analysis was to find out whether this variation is attributable to polymorphism
      at the DQ locus. As part of a nationwide prospective study including 757
      serologically HLA genotyped families, we determined HLA-DQ alpha and DQ beta
      restriction fragment polymorphisms in 17 selected families with important
      susceptibility haplotypes. Additionally, the DQA1 alleles were determined from 19
      haplotypes using sequence-specific oligonucleotide probes, and the DQB1 second
      exon was sequenced from nine haplotypes. The DR3 as well as DR4 positive
      haplotypes frequently found in Type 1 diabetic patients showed no variation at
      the HLA-DQ locus, and they were DQw2 and DQw8, respectively. The absolute risk
      for Type 1 diabetes for DR4,DQw8 positive haplotypes A2,Cw4,Bw35,DR4
      A3,Cw3,Bw62,DR4, A24,Cw7,Bw39,DR4, A2,Cw3,Bw62, DR4, and A2,Cw1,Bw56,DR4 was
      35/100,000, 130/100,000, 166/100,000, 196/100,000, and 218/100,000, respectively.
      The absolute risks for DR3,DQw2 positive haplotypes A1, Cw7,B8,DR3 and
      A2,Cw7,B8,DR3 were 68/100,000 and 103/100,000, respectively. These results
      provide further evidence that not only the polymorphism at the DQ locus but also
      other genes of the haplotypes contribute to susceptibility to Type 1 diabetes.

PMID- 1348714
TI  - Enzymatic and nonenzymatic cross-linking of collagen and elastin.
AB  - Knowledge regarding the steps and mechanisms related to the intra- and interchain
      cross-linking of collagen and elastin has evolved steadily during the past 30
      years. Recently, effort has been directed at identifying the location and types
      of cross-links that are found in collagen and elastin. There are two major groups
      of cross-links: those initiated by the enzyme lysyl oxidase and those derived
      from nonenzymatically glycated lysine and hydroxylysine residues. The formation
      of enzymatic cross-links depends on specific enzymes, amino acid sequences, and
      quaternary structural arrangements. The cross-links that are derived
      nonenzymatically occur more adventitiously and are important to pathobiological
      processes. Considerable progress has been made in elucidating the pathways of
      synthesis for several of the enzymatically mediated cross-links, as well as
      possible mechanisms regulating the specificity of cross-linking. Although less is
      known about the chemistry of cross-links arising from nonenzymatically glycated
      residues, recent progress has also been made in understanding possible
      biosynthetic pathways and control mechanisms. This review focuses on such
      progress and hopes to underscore the biological importance of collagen and
      elastin cross-linking.

PMID- 1348713
TI  - Dopaminergic mechanisms in the pathogenesis of schizophrenia.
AB  - The dopamine hypothesis of schizophrenia has been the dominant theoretical
      construction guiding research and treatment of the schizophrenic disorders over
      the past generation. This hypothesis, in its simplest guise, posits the presence
      of a functional alteration in central dopaminergic systems in the brains of
      schizophrenic patients. Recent findings have resulted in a greater understanding
      of the complexity of the central dopaminergic systems and have led to revisions
      of the hypothesis of a simple functional hyperactivity of central dopaminergic
      systems. These recent data suggest that there may be regionally restricted
      changes in the function of the mesotelencephalic dopamine system, and that these
      changes may be in opposite directions. Such changes may be associated with
      dysfunctions of interactions between distinct dopaminergic terminal field
      regions, and may be subserved by functional derangements in other transmitter
      systems or reflect regionally restricted changes in expression or function of
      distinct dopamine receptors or catecholamine synthetic enzymes. A recent FASEB
      symposium reviewed new advances in molecular biology, biochemistry, pharmacology,
      anatomy, and systems neuroscience as they relate to schizophrenia, and discussed
      the implications of these data for guiding future research and treatment
      strategies.

PMID- 1348715
TI  - FMRFamide-like immunoreactive nervus terminalis innervation to the pituitary in
      the catfish, Clarias batrachus (Linn.): demonstration by lesion and
      immunocytochemical techniques.
AB  - Certain thick FMRFamide-like immunoreactive fibers arising from the ganglion
      cells of nervus terminalis in the olfactory bulb of Clarias batrachus can be
      traced centripetally through the medial olfactory tract, telencephalon, lateral
      preoptic area, tuberal area, and hypothalamohypophysial tract to the pituitary.
      Following 6 days of bilateral olfactory tract transection, the immunoreactivity
      in the thick fibers, caudal to the lesion site, was partially eliminated, whereas
      after 10 and 14 days, it was totally abolished in the processes en route to the
      pituitary. The results indicate a direct innervation of the pituitary gland by
      the FMRFamide-like peptide containing fibers of the nervus terminalis.

PMID- 1348716
TI  - Adrenergic and dopaminergic regulation of gonadotropin-releasing hormone release
      from goldfish preoptic-anterior hypothalamus and pituitary in vitro.
AB  - The involvement of adrenergic and dopaminergic receptor subtypes on in vitro
      release of radioimmunoassayable gonadotropin-releasing hormone (GnRH) from
      incubated preoptic-anterior hypothalamic (P-AH) slices and pituitary fragments of
      sexually mature male goldfish was studied. Norepinephrine (NE) produced a dose
      related stimulation of GnRH from P-AH slices, but not from pituitary fragments.
      The effects of some adrenergic receptor agonists (1 microM) on GnRH release from
      P-AH slices were tested: phenylephrine (alpha 1-agonist) significantly stimulated
      GnRH release; clonidine (alpha 2-agonist) and isoproterenol (beta-agonist) were
      ineffective. Incubation of P-AH slices with phentolamine (alpha 1/alpha 2
      antagonist) and prazosin (alpha 1-antagonist), at a concentration of 1 microM,
      inhibited the release of GnRH induced by NE (60 microM); the alpha 2-antagonist
      yombibin and the beta-antagonist propanolol were ineffective. None of the
      adrenergic antagonists (1 microM) tested produced significant effects on
      spontaneous release of GnRH from both tissue preparations. Spontaneous release of
      GnRH from both P-AH slices and pituitary fragments was reduced by dopamine (DA)
      in a dose-related manner. The effects of some DA agonists (1 microM) were tested:
      apomorphine (D1/D2-agonist) and SKF 38398 (D1-agonist), but not bromocriptine and
      LY-171555 (D2-agonists) significantly reduced spontaneous GnRH release from P-AH
      slices in vitro. On the other hand, D2-agonists, but not D1-agonists,
      significantly reduced GnRH release from pituitary fragments. The effects of DA
      antagonists (1 microM) were also tested: in P-AH slices, addition of SKF-83566
      (D1-antagonist) significantly reduced spontaneous GnRH release; pimozide and
      domperidone (D2-antagonist) were ineffective when tested alone.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1348718
TI  - Current Cancer Therapy. Conference. Tampa, Florida, October 1990.

PMID- 1348717
TI  - Cloning, primary structure and regulation of the ARO4 gene, encoding the tyrosine
      inhibited 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Saccharomyces
      cerevisiae.
AB  - In Saccharomyces cerevisiae, two differently regulated 3-deoxy-D-arabino
      heptulosonate-7-phosphate (DAHP) synthase (DAHPS; EC 4.1.2.15) isoenzymes carry
      out the first step in the shikimate pathway. Mutations in both genes are
      necessary to cause aromatic amino acid (aa) auxotrophy, since one isoenzyme alone
      is sufficient to produce enough DAHP for normal growth of the cells. The
      phenylalanine-inhibited DAHPS is encoded by the previously isolated and
      characterized ARO3 gene. Here, we report the cloning and characterization of the
      ARO4 gene, encoding the second DAHPS, which is inhibited by tyrosine. The aa
      sequence of the ARO4 gene product reveals 76% similarity to the ARO3-encoded
      isoenzyme and 66 and 73% to the three DAHPS isoenzymes from Escherichia coli.
      ARO4 gene expression is regulated by the general control system of aa
      biosynthesis. As in the case of the ARO3 gene, a single GCN4-recognition element
      in the promoter is responsible for derepression of the ARO4 gene under aa
      starvation conditions. However, in contrast to the situation in the isogene,
      ARO3, GCN4 does not contribute to the basal level of ARO4 transcription under
      nonderepressing conditions.

PMID- 1348719
TI  - Advances in the chemotherapy of gynecologic malignancies.
AB  - Chemotherapy is playing an ever increasing role in the treatment of patients with
      the common gynecologic malignancies, including ovarian, cervical cancer, and
      endometrial cancer. Chemotherapy has its most defined role in the treatment of
      patients with ovarian cancer where virtually all patients will receive cytotoxic
      chemotherapy. There are four major areas of research in chemotherapy in
      gynecologic malignancies. In retrospective studies it has been demonstrated that
      dose intensity is an important factor in maximizing response rates. Clinical
      studies are now prospectively evaluating the importance of dose intensity,
      particularly with the new platinum analogue carboplatin. In addition, it has been
      demonstrated in endometrial cancer and cervical cancer that patients with poor
      prognostic features such as high grade tumours and large volume disease have a
      low probability of cure by standard modalities such as surgery and radiation. In
      this group of patients combined modality approaches are being evaluated. In
      addition, regional therapy, either in the form of intra-arterial therapy for
      patients with cervical cancer or intraperitoneal therapy for patients with
      ovarian cancer, is being investigated. The primary factor limiting the
      effectiveness of chemotherapy in gynecologic malignancies is the development of
      drug resistance. It has recently been demonstrated that several drugs such as
      taxol, ifosfamide, and hexamethylmelamine have activity in patients who have had
      previous treatment with platinum-based compounds. In addition, the mechanism
      associated with the development of drug resistance in ovarian cancer have
      recently been identified. Clinical trials have been initiated with compounds such
      as buthionine sulfoximine in an attempt to specifically reverse resistance
      associated with alkylating agents and platinum compounds.

PMID- 1348720
TI  - Proliferating cell nuclear antigen (PCNA) expression in formalin-fixed tissue of
      non-small cell lung carcinoma.
AB  - An immunohistochemical study of non-small cell lung carcinoma using PC10, a
      monoclonal antibody against PCNA, was performed on tissues routinely processed
      with formalin fixation and paraffin embedding. The PCNA labelling index and
      mitotic index were determined from sections of these tissues. Tumours showed a
      high mean PCNA labelling index of 53.3%. The mean mitotic index was 10.3/1000
      cells. Inter-examiner agreement of mitotic counting was good. A linear
      correlation between the PCNA labelling index and mitotic index was demonstrated
      (r = 0.71, P less than 0.00001). It is concluded that immunohistochemical nuclear
      labelling with anti-PCNA on routinely processed tissue is a simple technique for
      the assessment of proliferation in non-small cell lung carcinoma.

PMID- 1348721
TI  - The Pathology of Prostate Cancer--Part 2: Novel Aspects of Human Prostate Cancer
      Pathology. Symposium.

PMID- 1348722
TI  - [Expression of low-affinity Fc epsilon receptors on circulating monocytes in
      patients with inflammatory rheumatic diseases].
AB  - In patients with scleroderma, high proportions of circulating CD23+ monocytes
      could be detected by FACS analysis as compared with controls. Supernatants
      obtained from lymphocytes yielded high amounts of interleukin-4-(IL-4-)like
      activity. The results suggest that IL-4 contributes to monocyte activation in
      scleroderma. There were no correlations with serum IgE, or numbers of naive and
      memory-CD4+ lymphocytes.

PMID- 1348723
TI  - Characterization of F107 fimbriae of Escherichia coli 107/86, which causes edema
      disease in pigs, and nucleotide sequence of the F107 major fimbrial subunit gene,
      fedA.
AB  - F107 fimbriae were isolated and purified from edema disease strain 107/86 of
      Escherichia coli. Plasmid pIH120 was constructed, which contains the gene cluster
      that codes for adhesive F107 fimbriae. The major fimbrial subunit gene, fedA, was
      sequenced. An open reading frame that codes for a protein with 170 amino acids,
      including a 21-amino-acid signal peptide, was found. The protein without the
      signal sequence has a calculated molecular mass of 15,099 Da. Construction of a
      nonsense mutation in the open reading frame of fedA abolished both fimbrial
      expression and the capacity to adhere to isolated porcine intestinal villi. In a
      screening of 28 reference edema disease strains and isolates from clinically ill
      piglets, fedA was detected in 24 cases (85.7%). In 20 (83.3%) of these 24
      strains, fedA was found in association with Shiga-like toxin II variant genes,
      coding for the toxin that is characteristic for edema disease strains of E. coli.
      The fimbrial subunit gene was not detected in enterotoxigenic E. coli strains.
      Because of the capacity of E. coli HB101(pIH120) transformants to adhere to
      isolated porcine intestinal villi, the high prevalence of fedA in edema disease
      strains, and the high correlation with the Shiga-like toxin II variant toxin
      encoding genes, we suggest that F107 fimbriae are an important virulence factor
      in edema disease strains of E. coli.

PMID- 1348724
TI  - Ability of enteroaggregative Escherichia coli strains to adhere in vitro to human
      intestinal mucosa.
AB  - A collection of 44 enteroaggregative Escherichia coli (EAggEC) strains isolated
      from infants with diarrhea in India and the United Kingdom were examined for
      their ability to adhere in vitro to human intestinal mucosa and by electron
      microscopy for production of putative adherence factors. None of the strains
      adhered to human duodenal mucosa, and six strains tested did not adhere to ileal
      mucosa; all 44 strains, however, adhered to human colonic mucosa in localized
      aggregates. Electron microscopy of infected colonic mucosa indicated fimbrially
      mediated adhesion of the EAggEC strains. Four morphologically distinct kinds of
      fimbriae, including a new morphological type of E. coli fimbriae consisting of
      bundles of fine filaments, were identified among the EAggEC strains; this new
      type of fimbria was observed in 43 of the 44 EAggEC strains. Forty-three of the
      44 EAggEC strains were positive with a DNA probe developed to identify EAggEC,
      and most of the strains belonged to serotypes unrelated to the other major
      classes of diarrheic E. coli. These results suggest that EAggEC may be a large
      bowel pathogen and colonize the colon by a fimbrially mediated adhesion
      mechanism.

PMID- 1348726
TI  - Transformed rat pancreatic islet-cell lines established by BK virus infection in
      vitro.
AB  - Single-cell suspensions of primary rat pancreatic islet cells were infected with
      BK virus (BKV) prototype (Gardner) and the naturally occurring BKV strain (TU),
      isolated from human urine. These viral strains have different sequences in their
      non-coding control regions which contain promoter-enhancer elements and origin of
      DNA replication. Uninfected cell cultures disintegrated within 3 weeks, while a
      varying number of virus-infected cultures were immortalized and a majority
      exhibited focal areas of 2-dimensional growth. A significantly higher proportion
      of the BKV (TU)- than of the BKV (Gardner)-infected cultures were immortalized.
      Large tumor (T) antigen expression was evident in virus-infected cultures from
      day 4 post infection (p.i.), while insulin secretion decreased steadily during
      the first weeks of culture. Two cell lines were established from BKV (TU)
      infected cultures. Line 5A4 was contact-inhibited, growing as a dense monolayer,
      while 6A3 demonstrated foci of 2-dimensional growth. Both cell lines have
      retained their morphology and T-antigen expression for approximately 130
      passages. At high passages a low level of intracellular insulin, but no secretion
      into media, was detected. Based on standard biological tests (reduced serum
      requirements, growth at low cell density, anchorage-independent growth and tumor
      induction in nude mice) both cell lines have a fully transformed phenotype, but
      6A3 appears to be more malignantly transformed. Since both cell lines were
      established simultaneously from the same primary cells with the same virus batch,
      they provide an opportunity to study the transforming mechanisms of BKV in a
      relative context.

PMID- 1348727
TI  - Cardiac involvement in non-specific aorto-arteritis.
AB  - Cardiac involvement in 75 cases (mean age 21.1 +/- 6 years) with non-specific
      aorto-arteritis was studied. Detailed clinical examination, echocardiography and
      cardiac catheterization, including angiography, were done in all the cases, as
      was coronary angiography. Features of cardiac failure like sinus tachycardia,
      cardiomegaly, left ventricular third heart sound gallop and pulmonary congestion
      were detected in 27 cases with reduction of left ventricular ejection fraction
      (25-48%). Systemic hypertension was seen in 60 cases. Central aortic pressure,
      left ventricular systolic pressure and left ventricular end-diastolic pressure
      were increased in 66 cases. Pulmonary hypertension and increased pulmonary
      vascular resistance were detected in 6 cases. Aortic and mitral regurgitation
      were seen in 15 and 12 cases, respectively. Three patients had features of
      dilated cardiomyopathy such as generalized cardiomegaly, systemic and pulmonary
      congestion but without any cardiac murmurs and with normal central aortic
      pressure. The coronary angiogram revealed obstruction of the left anterior
      descending artery in 3 cases and right coronary artery obstruction in another 3
      cases. Histopathological studies revealed non-specific inflammatory changes with
      fibrosis in cardiac musculature and the great vessels.

PMID- 1348725
TI  - Urease-associated heat shock protein of Helicobacter pylori.
AB  - Helicobacter pylori urease is an extracellular, cell-bound enzyme with a
      molecular weight of approximately 600,000 (600K enzyme) comprising six 66K and
      six 31K subunits. A 62K protein is closely associated with the H. pylori urease,
      both in crude preparations and after gel filtration; this protein can be removed
      from the urease by ion-exchange chromatography without inactivating the enzyme.
      We purified this urease-associated protein and determined its N-terminal amino
      acid sequence. The sequence is 80% homologous (identical plus conserved amino
      acid residues) to the Escherichia coli GroEL heat shock protein (HSP), 75%
      homologous to the human homolog, and 84% homologous to the HSP homolog found in
      species of Chlamydia. Thus, the 62K urease-associated protein of H. pylori
      belongs to the HSP60 family of stress proteins known as chaperonins. Evidently
      this protein, HSP62, participates in the extracellular assembly and/or protection
      of the urease against inactivation in the hostile environment of the stomach.

PMID- 1348728
TI  - Estimates of fertility levels in a rural community of Saudi Arabia.
AB  - There is a dearth of information on fertility levels in Saudi Arabia. In the
      absence of a reliable vital registration system, fertility level can be estimated
      from sample surveys. The Gompertz relational fertility model has been fitted to
      parity data on 923 women from a survey in the Al-Baha region. The estimated total
      fertility rate was 8.4. Education and age at marriage have strong association
      with the level of fertility. Those who married at early ages had higher parities,
      whereas women who had more than primary education reported lower parities.

PMID- 1348729
TI  - Reproductive characteristics and contraceptive method choices of Nigerian women
      requesting terminal fertility control.
AB  - A choice of a safe and acceptable contraceptive method is an important concern
      for women who have completed their child-bearing intentions. This paper focuses
      on 557 women (mean age 35.9 years, mean number of living children 5.8 +/- 1.4,
      and mean number of living sons 3.1 +/- 1.3) who indicated some desire to limit
      childbearing, and were seen at the University of Ilorin Teaching Hospital, Family
      Planning Clinic in 1986/7. During this period, a wide and free choice of
      contraceptive methods, including the new subdermal levonorgestrel implant method
      (NORPLANT) and female surgical sterilization, was offered. Contraceptive method
      choices of women requesting terminal fertility control are: IUD 56%, injectables
      15.3%, female sterilization 11.5%, pills 8.6%, NORPLANT 8.1%, others 0.5%.
      Comparing terminal and nonterminal contraceptors, almost equal proportions
      adopted the IUD, 56% vs. 60.5%, while terminal contraceptors adopted the
      injectables and NORPLANT in significantly higher proportions. Within subgroups by
      contraceptive method, mean age and mean number of living children and of sons are
      not significantly different, though younger women tend to adopt the pill. Method
      choice of NORPLANT and tubal ligation was favoured by previous contraceptive use,
      but not by spousal approval. Years of education had a positive influence on the
      choice of NORPLANT. The program implications of these findings regarding
      selective counselling of terminal contraceptors, provision of long-lasting
      reversible contraceptive methods, and facilities for surgical sterilizations for
      men and women are discussed.

PMID- 1348730
TI  - Bilateral ectopic pregnancy.

PMID- 1348731
TI  - Laparoscopic salpingectomy using conventional laparoscopy equipment.
AB  - Laparoscopic surgery has gained wide acceptance in the treatment of ectopic
      pregnancy. When compared with conventional surgical techniques, the laparoscopic
      approach reduces perioperative morbidity, hospital costs, length of hospital
      stay, and recovery time. Laparoscopic surgery, however, often requires special
      surgical skills and expensive equipment. In this paper we review the literature
      on the efficacy of the laparoscopic approach to salpingectomy and report a simple
      technique for such a procedure. Any gynecologist who performs laparoscopic tubal
      sterilization by electrocautery has the necessary equipment and can develop the
      skills to carry out this procedure.

PMID- 1348732
TI  - Hemoperitoneum from a tubal pregnancy mimicking abruptio placentae: an
      obstetrical enigma.
AB  - A case of simultaneous intrauterine and extrauterine pregnancy with
      hemoperitoneum during labor is presented. The hemoperitoneum from the tubal
      pregnancy occurred sufficiently late during pregnancy to mimic a placental
      abruption. The difficulty of diagnosing heterotopic pregnancy is stressed.

PMID- 1348734
TI  - Common technical errors in hysterosalpingography.
AB  - Hysterosalpingograms from 100 consecutive patients referred for in vitro
      fertilization were reviewed to evaluate the adequacy of visualization of the
      uterine cavity. In 17 cases the hysterosalpingogram failed to demonstrate the
      entire uterine cavity. The most common reason for failure was an axial view of
      the uterus secondary to inadequate traction on the cervix in 82% (14/17) of the
      cases, followed by obstructed visualization of the lower uterine cavity and
      endocervical canal by the delivery catheter bulb in 21% (3/17). A speculum left
      in the vagina obscured visualization of the endocervical canal in 21% (3/17) of
      the cases. There were no significant differences in the mean number of
      radiographic exposures between the adequate and inadequate groups (4.7 vs. 5.9).
      This study suggests that failing (1) to remove the speculum before injecting
      contrast, (2) to evaluate the lower uterus and endocervix when using an
      intrauterine catheter, or (3) to place adequate traction on the cervix, may
      result in inadequate visualization of the uterine cavity and a need to repeat the
      study.

PMID- 1348733
TI  - Comparison of various therapies for the luteinized unruptured follicle syndrome.
AB  - A study was initiated to evaluate the prevalence of the luteinized unruptured
      follicle (LUF) syndrome in a group of 355 women with infertility. The diagnosis
      was established by carefully observing daily sonograms along with measuring
      estradiol, progesterone, and luteinizing hormone (LH) levels. Two distinct types
      of LUF syndrome were identified: mature follicle LUF, in which release of an ovum
      was not demonstrated after a follicle attained maturity (serum estradiol reached
      200 pg/mL while serum progesterone remained less than 2.5 ng/mL), versus
      premature luteinization LUF, where the serum progesterone increased above 2.5
      ng/mL before follicular maturation was attained. The use of either hCG alone or
      hCG in combination with hMG in a single injection at the time of follicular
      maturation successfully corrected mature follicle LUF in 21 of 46 patients (46%),
      whereas ovulation-inducing drugs plus hCG or hCG and hMG corrected LUF in 24 of
      25 patients (96%). Clomiphene citrate proved inferior to hMG in that it corrected
      LUF in 3 of 25 patients (12%) versus 12 of 22 patients (95%) who had undergone
      hMG therapy. Thus, hMG-hCG therapy is the most efficacious for mature follicle
      LUF, but because release can occur spontaneously on occasion by an appropriately
      timed single gonadotropin injection, one could offer the less costly options
      first. For premature luteinization, speeding up follicular maturation with
      gonadotropin therapy is effective. Upon failure of this technique, the more
      costly endogenous gonadotropin suppression followed by hMG can be employed.

PMID- 1348736
TI  - Effects of danazol on coagulant activity in the rat.
AB  - Coagulation factor activity was evaluated in female rats treated with danazol.
      Following 30 days of treatment, slight decreases in factor VII and X activities
      were noted. After 60 days, a prolongation of the prothrombin time, as well as a
      decrease in factor VII, was noted. The data suggest that in the rodent, danazol
      has minimal effects on coagulation activity.

PMID- 1348735
TI  - Some characteristics of azoospermic human semen.
AB  - Of 260 volume measurements and 265 fructose determinations on 257 azoospermic
      semen samples, the volume was normal (1-6 mL) in 78%, low in 16.7%, and high in
      5.2%. The percentage of azoospermic samples with low volume was greater than that
      found for samples containing sperm. Mean fructose concentrations were similar in
      high-volume and normovolemic azoospermic samples, but significantly lower in low
      volume samples. There was no correlation between (a) the etiology of the
      azoospermia and abnormal semen volume or fructose concentration (save for cases
      of obstruction and/or atrophic seminal vesicles) or (b) semen volume, fructose
      concentration, and serum LH, FSH, testosterone, or prolactin.

PMID- 1348737
TI  - Immunogenicity of deglycosylated zona pellucida antigens and their inhibitory
      effects on fertility in rabbits.
AB  - Influence of carbohydrates on the immunogenicity and immunocontraceptive
      potential of zona pellucida glycoproteins has been investigated in rabbits.
      Porcine zonae pellucidae, following deglycosylation with trifluoromethane
      sulfonic acid, retained significant immunogenic potential, as shown by the
      ability to generate antibodies which cross-reacted with the heterologous antigen.
      Antibody response, however, was much stronger against the native zona
      glycoproteins, thereby suggesting that both carbohydrate and protein moieties
      contribute to the overall immunogenicity of the zona pellucida antigens.
      Contraceptive efficacy of active immunization with the deglycosylated zona
      antigens, when evaluated by mating experiments, demonstrated inhibition of
      fertility in all immunized rabbits. Normal ovarian functions were disrupted in
      these animals, as revealed by the reduction in ovarian weights and gross
      impairment of folliculogenesis. Flushing of the oviducts of the immunized animals
      yielded a markedly reduced number of ova ovulated in response to hCG
      administration, none of which were fertilizable. Results collectively suggest
      that active heteroimmunization with deglycosylated zona pellucida antigens is
      effective in reducing fertility in rabbits.

PMID- 1348738
TI  - Fetal reduction: is this the appropriate answer to multiple gestation?

PMID- 1348739
TI  - An injection of meperidine and an anti-nausea agent such as promethazine or
      prochlorperazine.

PMID- 1348740
TI  - The alcohol dehydrogenase polymorphism in natural populations of Drosophila
      melanogaster: ADH activity variation restriction site polymorphism and the Adh
      cline.
AB  - Alcohol dehydrogenase activity has been measured in 186 iso-second chromosome
      lines--104 from seven Australian populations and 82 from six Chinese populations.
      Restriction endonuclease variation in the Adh gene region in these lines has
      previously been described (Jiang & Gibson, 1991). The mean ADH activity of AdhF
      and AdhS lines was significantly higher in the Chinese samples than in the
      Australian samples. In each population on both continents the mean activity of
      the AdhF lines is significantly higher than that of the AdhS lines. Six lines
      homozygous for a thermostability variant, AdhFChD (detected in four of the
      Chinese populations), had intermediate levels of ADH activity and protein amount.
      In a subset of the lines with the highest and lowest levels of ADH, there was a
      correlation of 0.69 between ADH activity and ADH CRM. None of the restriction
      site variants was consistently associated with the amount of ADH activity.
      Associations between BamHI (-7.2), the Adh polymorphism and ADH activity suggest
      that there are modifiers of ADH 5' to the gene. The deletion (0.2) at position 
      2.8 on the restriction map (Jiang & Gibson, 1991) was associated with increased
      levels of ADH activity in AdhS lines from China. Two unique insertions in the
      gene region were associated with low activity in AdhF lines and a null activity
      allele had a deletion removing most of exon 2. A single line with a duplication
      of a part of the Adh coding region and of the 5' regulatory section had
      relatively high ADH activity. Considering all the data, the main factor affecting
      ADH activity levels in populations is the frequency of AdhF.

PMID- 1348742
TI  - HLA-DP distribution in Shanghai Chinese--a study by polymerase chain reaction-
      restriction fragment length polymorphism.
AB  - One hundred and four normal unrelated Chinese were typed for HLA-DPA1 and DPB1
      alleles by polymerase chain reaction-restriction fragment length polymorphism.
      Increased frequencies of HLA-DPA1*0201 and DPB1*0501 were found in this Chinese
      population as compared with those detected in Caucasoids and blacks.

PMID- 1348741
TI  - Detection of tyrosine hydroxylase and phenylethanolamine-N-methyltransferase
      messenger RNAs in the mouse adrenal gland and the brain by in situ hybridization.
AB  - To study the expression of tyrosine hydroxylase (TH) and phenylethanolamine-N
      methyltransferase (PNMT) genes in the mouse adrenal gland and the brain, we
      performed in situ hybridization studies by using several types of complementary
      DNA probes recognizing coding regions of human TH (THc), the 3'-end of the human
      region of TH (TH3'), and the coding region of the human PNMT (PNMTc). THc mRNA
      was detected in the chromaffin cells of the mouse adrenal medulla and brain
      catecholaminergic neurons including the substantia nigra and ventral tegmental
      area. TH-immunopositive neurons were located in a similar pattern in adjacent
      sections. However no positive signals were detected by the TH3' probe. Using the
      PNMTc probe, the majority of cells in the adrenal medulla demonstrated positive
      labelling. Although the mouse TH and PNMT genes have not been fully isolated and
      sequenced, the present study strongly suggests that the sequence of the coding
      regions of TH and PNMT are similar in human and mouse. The THc and PNMTc probes
      are particularly useful in investigating the loci of gene transcription in mouse
      tissues.

PMID- 1348744
TI  - Polymerase chain reaction--single-strand conformation polymorphism analysis of
      polymorphism in DPA1 and DPB1 genes: a simple, economical, and rapid method for
      histocompatibility testing.
AB  - A new technical trial was carried out to detect polymorphism in HLA-DP genes,
      based on the diversity in electrophoretic mobility of single-stranded DNA (single
      strand conformation polymorphism, SSCP). Genomic DNAs from 31 cell lines
      homozygous for 2 and 14 different DPA1 and DPB1 alleles, respectively, and from
      peripheral blood cells of a normal individual homozygous for another DPB1 allele
      were subjected to polymerase chain reaction (PCR) to amplify the polymorphic exon
      2 of DPA1 or DPB1 genes. The PCR samples were denatured by heating in the
      presence of formamide to obtain single-stranded DNA, electrophoresed in a neutral
      polyacrylamide gel, and visualized by silver staining. Allelic differences were
      detected by the distinctive electrophoretic pattern of each single strand,
      depending on the sequence-specific conformation. Fifteen DPB1 alleles showed 11
      distinct electrophoretic patterns, leaving four allelic combinations not
      distinguished. These four allelic combinations could be further distinguished by
      using another couple of primers in PCR, with which a part of the exon was
      amplified, and by subsequent SSCP analysis. The use of four pairs of primers in
      PCR allowed for discrimination of all the 15 DPB1 alleles tested. Two allelic
      differences in exon 2 of DPA1 gene could be clearly demonstrated. In addition,
      putative new alleles of DPA1 and DPB1 genes were detected by SSCP analyses. The
      PCR-SSCP analysis is simple and rapid, requires neither radioactive materials nor
      restriction enzymes, and is expected to be a useful tool for investigating the
      fine HLA-matching required for clinical transplantation of organs.

PMID- 1348743
TI  - Extensive study of DRB, DQA, and DQB gene polymorphism in 23 DR2-positive,
      insulin-dependent diabetes mellitus patients.
AB  - To gain insight into the HLA subregions involved in protection against insulin
      dependent diabetes mellitus (IDDM) we investigated the polymorphism of HLA-DR and
      -DQ genes in 23 DR2 IDDM patients. Results show the following. (1) Fourteen
      patients (61%) possess the DRB1, DRB5, and DQB1 alleles found in DRw16/DQw5
      healthy people. These data contrast with the 5% of DRw16 normally found in DR2
      populations and are in agreement with former observations supporting that the
      DRw16 haplotype is not protective. (2) Nine DR2 patients, i.e., 39% versus 95% in
      published DR2 controls, possess the DRB alleles found in DRw15 unaffected people.
      Among them, six patients have also DQA1 and DQB1 alleles identical to those found
      in DRw15/DQw6 healthy individuals. These data confirm that the DRw15/DQw6
      haplotype is protective but indicate that none of the DR or DQ alleles, alone or
      in association, confers an absolute protection. (3) Our most striking results
      concern the very high frequency of recombinant haplotypes among the DRw15
      patients: 3 of 9. In these three patients recombinations led to the elimination
      of both DQB1 and DQA1 alleles usually associated with DRw15. This strongly
      suggests that the occurrence of IDDM in these DRw15 patients is due to the
      absence of the usual DQ product and thus reinforces the assumption that DQ rather
      than DR region is involved in the protection conferred by the DRw15/DQw6
      haplotype. Finally, analysis of the non-DRw15 haplotypes in heterozygous patients
      showed that IDDM can occur in the absence of any DQ alpha beta heterodimer of
      susceptibility.

PMID- 1348746
TI  - Ligand binding to the porcine adipose tissue beta-adrenergic receptor.
AB  - We measured ligand binding to the beta-adrenergic receptor from porcine
      adipocytes using tritiated radioligands, dihydroalprenolol (DHA) and CGP-12177
      (CGP), and an iodinated radioligand, cyanopindolol (ICP). Binding was measured in
      a crude plasma membrane preparation. Equilibrium saturation binding was regular
      for all three ligands; the Kd were approximately 4,000 pM for DHA, 600 pM for
      CGP, and 100 pM for ICP. Binding was stereospecific with each radioligand.
      Association of each radioligand was relatively rapid; dissociation was rapid and
      complete for DHA, initially rapid but ultimately incomplete for CGP, and minimal
      for ICP. The Kd estimated from kinetic data were approximately 1,000 pM for DHA
      and 100 pM for CGP. The receptor did not bind phentolamine, an alpha-adrenergic
      antagonist, except at concentrations greater than 10(-5) M. Propranolol was bound
      to the receptor with a Ki of approximately 8 nM regardless of the radioligand
      used. Metoprolol, a purported beta 1-adrenergic specific antagonist, was bound to
      the receptor with a Ki of approximately 300 nM when the radioligands were CGP or
      ICP but with a Ki of approximately 1,000 nM when the radioligand was DHA. The Ki
      for ICI 118,551, a purported beta 2-adrenergic specific antagonist, were
      approximately 500 nM when the radioligands were DHA or CGP but 125 nM when the
      radioligand was ICP. Thus, the choice of radioligand can influence the
      characterization of the beta-adrenergic receptor being studied.

PMID- 1348745
TI  - Effects of growth hormone-releasing factor and feed intake on energy metabolism
      in growing beef steers: net hormone metabolism by portal-drained viscera and
      liver.
AB  - Effects of growth hormone-releasing factor (GRF) and intake on arterial
      concentrations and net visceral metabolism of hormones were measured in six
      growing Hereford x Angus steers using a split-plot design with 4-wk injection
      periods within 8-wk intake periods. Steers were fed a 75% concentrate diet at two
      intakes and were injected s.c. twice daily with saline or GRF (10 micrograms/kg
      of BW). Arterial concentrations of growth hormone (GH) were measured on d 1 and d
      8 to 10 of injections. Eleven measurements, obtained at 30-min intervals, of
      arterial concentration and net flux of hormones across portal-drained viscera
      (PDV) and liver were obtained on d 8 to 10 of injections (six hourly measurements
      were used for insulin-like growth factor-I [IGF-I] and somatostatin). The area
      under the GH curve and average and peak GH concentrations were increased (P less
      than .01) by GRF and were greater (P less than .10) at low than at high intake.
      Liver removal of GH was not affected by GRF or intake. Arterial IGF-I
      concentration was increased (P less than .05) by GRF and not affected by intake.
      Treatments did not affect IGF-I flux across the liver. Arterial insulin
      concentration was greater (P less than .05) at high than at low intake, in part
      because of greater (P less than .01) PDV release. Increased (P less than .10)
      arterial insulin concentration in GRF-treated steers was not attributable to
      significant changes in PDV or liver net flux. Arterial glucagon concentration was
      greater (P less than .01) at high than at low intake, in part because of greater
      (P less than .05) PDV glucagon release and decreased (P less than .10) liver
      extraction ratio. Effects of intake on arterial concentration of insulin and
      glucagon were in part due to changes in visceral metabolism, but GRF did not
      affect PDV or liver hormone metabolism.

PMID- 1348747
TI  - Determination of an antipsychotic agent (ICI 204,636) and its 7-hydroxy
      metabolite in human plasma by high-performance liquid chromatography and gas
      chromatography-mass spectrometry.
AB  - ICI 204,636 (I) is an orally active antipsychotic agent under development for the
      treatment of schizophrenia in humans. It is partially converted in animals to an
      active 7-hydroxy metabolite (II). Methods were developed for the simultaneous
      determination of both analytes in human plasma using high-performance liquid
      chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). The
      analytes were extracted from plasma using phenyl solid-phase extraction columns.
      Quantification by isocratic HPLC was performed in the reversed-phase mode with
      detection at 250 nm. Extracts were derivatized to trimethylsilyl ethers for
      quantification by GC-MS using selected-ion monitoring. Both assays were evaluated
      for consistency of response, precision, accuracy and specificity. Limits of
      quantification for I and II by HPLC were 15 and 20 ng/ml, respectively; limits of
      quantification for I and II by GC-MS were 2 and 5 ng/ml, respectively. Both
      methods were applied to the analysis of clinical samples from oral dosing studies
      with I.

PMID- 1348748
TI  - High-performance liquid chromatography-electrochemical detection of vecuronium
      and its metabolites in human plasma.
AB  - A high-performance liquid chromatographic assay coupled with electrochemical
      detection has been developed for the determination of vecuronium and its three
      putative deacetylated metabolites in human plasma. A novel solid-phase extraction
      procedure allowed good recovery of both vecuronium and its metabolites, together
      with ease and speed of execution. This method was sensitive, reproducible and
      accurate over the therapeutic range of concentrations of vecuronium and its
      metabolites, and was applied successfully to a study of the pharmacokinetics of
      vecuronium in anaesthetized patients.

PMID- 1348749
TI  - Correlation of gingival crevicular fluid proteases with clinical and radiological
      measurements of periodontal attachment loss.
AB  - Probing attachment loss and radiographical measurements of bone loss were made on
      20 untreated chronic periodontitis patients. At a second visit, gingival
      crevicular fluid was collected on filter paper strips from the deepest accessible
      interdental probing site of each tooth. Gingival crevicular fluid volumes were
      determined and the samples eluted into buffer. Protease activities in the
      resulting eluates were assayed with peptidyl derivatives of 7-amino-4
      trifluoromethyl coumarin (AFC). Cathepsin B/L-like activity was determined with
      Bz-Val-Lys-Lys-Arg-AFC, elastase-like activity with MeOSuc-Ala-Ala-Pro-Val-AFC,
      tryptase-like activity with Z-Ala-Ala-Lys-AFC, trypsin-like activity with Z-Gly
      Gly-Arg-AFC and dipeptidyl peptidase IV-like activity with Ala-Pro-AFC. Total
      enzyme activities and enzyme concentrations correlated positively with probing
      attachment loss and bone loss in linear regression analysis. This was true at
      both a patient level, using mean patient values, and a site level, using either
      individual patient or pooled patient data. All of these correlations were highly
      statistically significant for site comparisons. In inter- and intra-patient
      comparisons the proportion of significant correlations was greater for total
      enzyme activity than concentration. Clinical and radiological measurements of
      attachment loss showed generally similar levels of correlation. Total enzyme
      activities had good specificity and sensitivity as indicators of attachment loss
      in this cross-sectional study. The results support further investigation of the
      diagnostic potential of gingival crevicular fluid proteases in evaluation of the
      periodontal condition.

PMID- 1348750
TI  - Mechanisms of early death despite thrombolytic therapy: experience from the
      Thrombolysis in Myocardial Infarction Phase II (TIMI II) study.
AB  - Mechanisms of death among patients who died within 18 h of enrollment in the
      Thrombolysis in Myocardial Infarction Phase II (TIMI II) study were analyzed. Of
      3,339 patients enrolled, 32 died within the 1st 4 h and 31 died within the
      subsequent 14 h. Thirteen of the 63 patients had shock at enrollment; 22 had
      advanced hemodynamic compromise without shock and 28 initially had minimal to no
      compromise. Prior infarction was present in 16 patients (25%). Pump failure was
      responsible for 39 early deaths (62%), ventricular rupture for 10 (16%),
      arrhythmia for 8 (13%) and complications of therapy for 6 (10%). Nine of 720
      patients randomized to immediate intravenous beta-adrenergic blocking agent
      therapy had an early death compared with 6 of 714 assigned to deferred beta
      blocker therapy. Thus, mortality is highest in the early hours after myocardial
      infarction, even in patients treated with thrombolytic therapy and is most
      frequently due to pump failure. These results imply that efforts to reduce
      mortality during this critical time period should be directed at prevention,
      limitation or palliation of early pump failure.

PMID- 1348751
TI  - Influence of histamine receptors on basal left ventricular contractile tone in
      humans: assessment using the H2 receptor antagonist famotidine and the beta
      adrenoceptor antagonist esmolol as pharmacologic probes.
AB  - Histamine has a positive inotropic action in humans. Recent controversial data
      have suggested that histamine2 (H2) receptor blockade depresses overall left
      ventricular systolic performance in healthy volunteers. To explore the
      possibility that H2 receptors positively influence basal left ventricular
      contractile tone, 10 normal subjects were studied by using imaging and Doppler
      echocardiography and calibrated subclavian pulse data in a blinded, randomized,
      two-period crossover trial with measurements obtained at the end of each 7-day
      period. Oral drug administration consisted of either the potent H2 antagonist
      famotidine (40 mg/day) or placebo. Left ventricular circumferential end-systolic
      wall stress-rate-corrected velocity of fiber shortening (Vcfc) relations were
      generated over a range of loads with methoxamine. Contractility was assessed by
      using Vcfc at a common end-systolic wall stress. During each study, data were
      obtained before and during high dose intravenous esmolol administration to
      determine the contributions, if any, of sympathetic reflex responses. Famotidine
      did not alter blood pressure, left ventricular percent fractional shortening,
      circumferential end-systolic wall stress, stroke volume index, cardiac index,
      total vascular resistance or ventricular contractile state in comparison with
      placebo but did decrease heart rate by 3 beats/min (p less than 0.05). With beta
      adrenergic blockade, no differences in contractility were evident between esmolol
      alone and famotidine plus esmolol. Thus, H2 receptor blockade with famotidine
      does not alter myocardial mechanics or cardiac sympathetic tone, suggesting that
      in humans basal left ventricular contractile state is not physiologically
      dependent on the H2-mediated effects of histamine.

PMID- 1348752
TI  - Diurnal exposure profile in rats from dietary administration of a chemical
      (doxazosin) with a short half-life: interplay of age and diurnal feeding pattern.
AB  - Doxazosin, an alpha-adrenergic blocking agent, has a plasma half-life in male
      rats of 1-2 h after i.v. administration. Plasma concentrations of doxazosin were
      measured in male rats receiving the drug mixed in the diet at dose levels from 5
      to 40 mg kg-1. Samples taken at 4-h intervals during the light (0700-1900) and
      dark phases revealed peak concentrations at 0400 which were only about three
      times higher than the trough concentrations observed ca. 12 h later. The 24-h
      area under the curve (AUC) values increased disproportionately with dose and with
      age from 2 months up to 8 months of age; thereafter they were fairly stable to 24
      months of age. This age-related effect may have been due to a reduction in
      clearance and/or a change in the feeding pattern of the rats. Young rats consumed
      ca. 84% and old rats only 45% of their daily feed during the nocturnal (active)
      phase. Given the known diurnal rhythms in absorption, protein binding and enzyme
      metabolising activity, such a change in feeding pattern with age may have wider
      toxicokinetic implications.

PMID- 1348753
TI  - Topically active drugs in the treatment of peptic ulcers. Focus on colloidal
      bismuth subcitrate and sucralfate.
AB  - Topically active agents (i.e., colloidal bismuth subcitrate and sucralfate) have
      proved to be effective in promoting the healing of both gastric and duodenal
      ulcers and in relieving ulcer symptoms. Sucralfate alone has also been shown to
      maintain peptic ulcers in remission when taken continuously for a long period of
      time, whereas successful short-term therapy with bismuth subcitrate is associated
      with a more prolonged remission of duodenal ulcer disease when compared to H2
      blockers. The antiulcer efficacy of these agents is partially counteracted by the
      need for multiple daily administrations, which requires greater patient
      compliance than with H2 antagonists. A specific subgroup of patients who might
      particularly benefit from these drugs are those with duodenal ulcer resistant to
      H2 blockers, whereas chronic nonsteroidal antiinflammatory drug users with peptic
      ulcer respond to therapy with site-protective agents as well as to antisecretory
      drugs.

PMID- 1348754
TI  - A review of hospitalized patients with bacterial gastroenteritis.
AB  - The distribution and clinical management of thirty-two hospitalized patients with
      salmonella and campylobacter infections were reviewed and the impact of these
      infections on hospital resources was assessed. Eighteen patients with salmonella
      infection had an age and sex distribution comparable with the community cases. In
      contrast, 10 out of 14 (71.4%) patients with campylobacter infection were under
      20 years of age though the peak incidence of the infection in the community
      occurred in the 21-65 years age group (67%). There was no male predominance. The
      median duration of stay in hospital was 6 days for patients with salmonella
      infection and 3 days for those with campylobacter infection. Physicians were
      inconsistent in the treatment of campylobacter infection. Overall the financial
      impact of managing patients with salmonella and campylobacter infection was
      considerable (1384 pounds and 779 pounds respectively per patient). A limitation
      on unnecessarily prolonged hospital stays and the establishment of clear
      guidelines for the clinical management of these infections are necessary.

PMID- 1348755
TI  - Ten years' experience with methicillin-resistant Staphylococcus aureus in a large
      Australian hospital.
AB  - The Royal Brisbane Hospital (RBH) is a 1200-bed teaching hospital with acute,
      general and specialist units for adult patients. Methicillin-resistant
      Staphylococcus aureus (MRSA) was first detected at the RBH in 1975 and the number
      of new patients colonized and infected increased from one in 1975 to 720 in 1989,
      with a peak of 811 in 1987. Virulence may be inferred from blood culture
      isolates. Between 1979 and 1989 the number of patients with S. aureus bacteraemia
      increased from 40 to 138 per year. The percentage of these isolates which were
      MRSA varied from a low of 4% in 1980 to a peak of 37% in 1984 with 28% in 1989.
      The control attempts, sensitivity patterns, sources of the isolates and their
      probable impact and importance will be discussed.

PMID- 1348757
TI  - Mycotic prosthetic-valve endocarditis.

PMID- 1348756
TI  - Hospital-acquired meningococcaemia.

PMID- 1348758
TI  - Transmission of chickenpox to two intensive care unit nurses from a liver
      transplant patient with zoster.

PMID- 1348759
TI  - Sterilization of arthroscopes and laparoscopes.

PMID- 1348761
TI  - Reduction of inappropriate antimicrobial use rates in a hospital in Porte Alegre,
      Brazil.

PMID- 1348760
TI  - Chlorhexidine sensitivity of Enterococcus faecium resistant to vancomycin, high
      levels of gentamicin, or both.

PMID- 1348762
TI  - Surface hydrophobicity as an indicator of pathogenicity of the coagulase negative
      staphylococci.

PMID- 1348763
TI  - Hospital outbreak of multiresistant Streptococcus pneumoniae.

PMID- 1348764
TI  - Re-use of irrigating equipment for cystoscopy.

PMID- 1348765
TI  - Vascular catheter-related sepsis: diagnosis and prevention.
AB  - Although catheter-related sepsis (CRS) is an important cause of nosocomial
      infection and the major complication of intravenous catheter use, there is, as
      yet, no consensus concerning either a useful definition of CRS or the optimal
      method of catheter management and prevention of infection. Semiquantitative
      culture of catheter tips is a useful method of diagnosis of CRS but other
      techniques such as quantitative catheter blood cultures and Gram staining of the
      catheter have roles in selected patients. The most significant impact on the
      prevention of CRS is made by the introduction of an intravenous therapy team. The
      site and method of catheter insertion, type of dressing and antisepsis, catheter
      flushing and use of prophylactic antibiotics are also important issues.
      Techniques such as guide-wire exchange and catheters such as triple lumen and
      total implantable venous access devices have their own infection problems. Many
      new and interesting approaches to the prevention of CRS are being formulated. To
      facilitate further progress, a standardized definition for diagnosis, and revised
      recommendations for prevention of CRS would be helpful.

PMID- 1348766
TI  - Evaluation of the efficacy of surgical hand disinfection following a reduced
      application time of 3 instead of 5 min.
AB  - The guidelines of the German Society for Hygiene and Microbiology for the
      evaluation of disinfectants suggest an application time of 5 min for surgical
      scrub products. In a comparative investigation, which included the more important
      basic substances and agents, tests were carried out to investigate whether it was
      possible to reduce the application time to 3 min without losing efficiency in
      both the immediate as well as the prolonged effect of bacterial reduction. It was
      found that this could be achieved by certain products, depending on the formula
      and type of active substance. Thus, a reduced application time of 3 min can be
      considered for the evaluation of surgical scrub disinfectants for national and
      international guidelines.

PMID- 1348767
TI  - Investigation of an outbreak of nosocomial infection due to a multiply drug
      resistant strain of Pseudomonas aeruginosa.
AB  - A nosocomial outbreak of Pseudomonas aeruginosa infections which occurred in the
      Urology Service of a large city hospital was studied. A case-control methodology
      was used to analyse patients' characteristics and the main risk factors of all
      cases with a positive culture during the period between March 1987 and March
      1988. The usefulness of factor analysis in the definition of a case was examined.
      There were 74 infections of which 35 (47.3%), had a nosocomial origin. The
      outbreak took place in December 1987, with a peak incidence of infections of
      10.5%, compared with a 2.2% frequency during the preceding months (P less than
      0.005). Six of the nine infections occurring in that month, were caused by
      strains resistant to ticarcillin and gentamicin. The epidemic cases had longer
      hospital stays than the non-epidemic cases (P less than 0.038) and occurred more
      frequently in a specific area of the hospital (P less than 0.001). The odds ratio
      for resistance to gentamicin was 15 (P less than 0.018) and that of resistance to
      ticarcillin, 127 (P less than 0.0001). Our results suggest that inaccurate case
      definitions may produce misleading conclusions. Factor analysis appears to be a
      useful analytical tool when defining a case.

PMID- 1348768
TI  - Outbreak of infection in two UK hospitals caused by a strain of Klebsiella
      pneumoniae resistant to cefotaxime and ceftazidime.
AB  - During an 8-month period, Klebsiella pneumoniae resistant to cefotaxime and
      ceftazidime were isolated from 18 elderly patients in two closely-situated UK
      hospitals. Amongst these 18 patients, the organisms were isolated from urine
      samples of 17, from blood cultures of two and from a wound swab of one. The
      infected patients were located in nine different wards and several of the
      patients had been transferred between wards, within and between the two
      hospitals. All the bacterial isolates belonged to serotype K62, were non-typable
      or reacted only weakly with bacteriophage, showed similar plasmid profiles and
      were resistant to tetracycline and trimethoprim, thus indicating they were the
      same strain. Resistance to cefotaxime and ceftazidime was inhibited by clavulanic
      acid suggesting the involvement of extended-spectrum beta-lactamase (ESBL) enzyme
      activity. This was confirmed by analytical isoelectric focusing, which showed
      that isolates each produced two beta-lactamases with isoelectric points of
      7.0(SHV-3) and 7.6 (SHV-1/2) respectively.

PMID- 1348769
TI  - Enterobacter in hospital.

PMID- 1348770
TI  - A clinical evaluation of glove washing and re-use in dental practice.
AB  - This study has assessed the durability of four brands of latex gloves, Ansell
      Medical 'Medi-Grip', Regent 'Biogel D', Surgikos 'Microtouch' and the London
      Rubber Company 'Supreme', under conditions of repeated washing and re-use in a
      clinical dental setting. The microbiological effectiveness of 'Hibiscrub' as a
      decontaminating washing agent was examined simultaneously. Examination by an
      electrical test for micropunctures in 200 unused gloves of each brand revealed
      such defects in 6(3%) of Ansell 'Medi-Grip', 3(1.5%) of 'Biogel D', 14(7%) of
      Surgikos 'Microtouch' and 2(1%) of LRC 'Supreme' gloves. Following repeated
      clinical use, micropunctures were detected in 18% of Ansell 'Medi-Grip', 10% of
      'Biogel D', 75% of Surgikos 'Microtouch' and 56% of LRC 'Supreme'. Microorganisms
      were isolated from the glove surfaces after 45% of the occasions on which the
      gloves were washed for 1 min in 'Hibiscrub' (ICI Dental). Eighty-five per cent of
      these isolates were environmental organisms, but oral streptococci were isolated
      from 8.4% of the pairs of gloves examined. The high rate of micropuncture
      development following repeated washing and re-use of latex gloves indicates that
      they cannot effectively perform their barrier function under such conditions. The
      microbiological data have also revealed the potential for cross-infection between
      patients through inadequate decontamination of glove surfaces. For operative
      dental surgery, the results suggest that heavier, surgical type gloves are to be
      preferred, and that multiple use of any glove type should be discouraged.

PMID- 1348771
TI  - Test models for hygienic handrub and hygienic handwash: the effects of two
      different contamination and sampling techniques.
AB  - Two methods for artificial contamination of hands and two sampling techniques to
      recover the test organisms were compared for their effects on the results of two
      post-contamination hand treatments: a handrub with two portions of 3 ml of 2
      propanol 60% v/v for 1 min, and a handwash with liquid soap 20% w/v for 1 min
      followed by a 15 s rinse. The two contamination methods involved a short
      immersion of the hands (up to the middle of the mid-hand) in a suspension of the
      test organism followed by either air-drying (3 min) or drying by rubbing the
      hands' vigorously against each other (3 min) in a standardized way. The two
      sampling techniques consisted of rubbing the fingertips in either 10 ml
      trypticase soy broth (TSB) against the bottom of a Petri dish; or 100 ml TSB
      against glass beads contained in a bowl. Sixteen volunteers were randomly
      allotted to four blocks of four. They carried out the four possible combinations
      of two treatments and two contamination methods in a series of four tests
      arranged in a Latin-square design. In addition, the two sampling techniques were
      compared with each other concurrently by sampling of the right and left hand each
      with a different one of the two techniques. The alcoholic handrub reduced the
      release of test organisms significantly (2P less than 0.005) more effectively, by
      1.1-1.3 x log10, than did the handwash with liquid soap, regardless of the
      contamination or sampling method. Whereas the two recovery techniques yielded
      virtually identical results in corresponding situations, the method of artificial
      contamination affected the mean reduction factors, strongly.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1348772
TI  - Importance of medium and atmosphere type to both slime production and adherence
      by coagulase-negative staphylococci.
AB  - Marked differences in both the production of slime and adherence by
      Staphylococcus epidermidis were observed when comparing four culture media. Slime
      isolated from a strain cultured in a chemically defined medium (HHW) in air was
      chemically indistinguishable from that formed in both HHW and synthetic dialysis
      fluid (SDF) in air with 5% CO2. The presence of a physiological level of CO2
      during culture in tryptone soya broth (TSB) prevented production of slime. It was
      not possible to separate the constituents of slime from those of the culture
      medium in bacteria grown in TSB in air using DEAE cellulose. Slime production was
      notably poor in used peritoneal dialysis fluid (PUD). Adherent growth was marked
      in HHW and SDF but was poor in TSB and PUD when air with 5% CO2 was used. These
      findings emphasize the advantages in using chemically defined and biological
      fluids when studying slime production and adherence by S. epidermidis.

PMID- 1348773
TI  - Controlled trial of a Y-set dialysis delivery system to prevent peritonitis in
      patients receiving continuous ambulatory peritoneal dialysis.
AB  - Peritonitis rates were compared in patients receiving continuous ambulatory
      peritoneal dialysis (CAPD) via either a Y-set dialysate delivery system or a
      standard system. Forty patients in each arm of the trial were matched for age
      (range 20-67 years, mean 49 years), and remained in the study for similar periods
      (range 3-36 months, mean 14.1 months). The observation time was 564 patient
      months for each arm of the trial. There were 22 episodes of peritonitis in nine
      out of 40 patients using the Y-set and 57 episodes in 21 out of 40 patients using
      the standard system (P = 0.005 Wilcoxon signed rank test for episodes, P = 0.02
      McNemar's chi 2 test for patients). Peritonitis rates were one episode per 25
      patient-months in the Y-set group, and one episode per 9.7 patient-months in the
      standard group. In the Y-set group there were significantly fewer episodes caused
      by coagulase-negative staphylococci and Acinetobacter spp. There was no
      difference in the rate of episodes caused by Staphylococcus aureus, streptococci,
      enterococci, corynebacteria, enterobacteria or pseudomonads. There was no
      difference in the incidence of catheter exit wound infections. The Y-set dialysis
      delivery system is effective in reducing peritonitis rates in CAPD patients
      caused by organisms derived from the commensal skin flora, principally coagulase
      negative staphylococci, but does not reduce peritonitis caused by other
      organisms.

PMID- 1348774
TI  - Laboratory evaluation of a filter for the control of cross-infection during
      pulmonary function testing.
AB  - Nosocomial transmission of respiratory pathogens is a possible complication of
      lung function testing. The use of a filter, placed between the patient and the
      spirometer equipment may be one way of preventing such nosocomial spread. This
      paper reports the laboratory evaluation of the efficiency of such a filter at
      removing bacteria from exhaled breath. Volunteers exhaled 100 normal breaths or
      four forced exhalations through a filter on to a blood agar plate. Bacterial
      counts on the agar plate were compared with recoverable bacterial counts from the
      filter. Total challenge from the forced exhalations ranged from 161-84,200 colony
      forming units. The calculated efficiency of 10 volunteers was 99.9%. For the
      normal breaths the challenge ranged from 0-262,000 colony forming units. There
      was no growth on any of the blood-agar plates. These filters appear to be highly
      efficient at removing exhaled bacteria.

PMID- 1348775
TI  - Epidemiology of Pseudomonas aeruginosa in an intensive care unit using selective
      decontamination of the digestive tract.
AB  - Selective decontamination of the digestive tract (SDD) aims to reduce the rate of
      nosocomial infections in critical care patients. Pseudomonas spp. are common
      nosocomial pathogens and in this study isolates collected from patients and the
      environment during an SDD trial were examined. The study enrolled 161 SDD cases
      and 170 controls. Pseudomonads were isolated from 27% of SDD patients and 30% of
      controls. SDD partially suppressed colonization in the 'gastro-respiratory'
      mucosae but not in the rectum. A total of 108 isolates of pseudomonads were
      recovered from the environment. Resistance in rectal isolates was minimal but
      isolates from 'gastro-respiratory' sites showed increasing aminoglycoside
      resistance. Eighty-six per cent of aminoglycoside-resistant isolates from both
      patient groups and environment were pyocine type 1x. Episodes of infection were
      reduced in the SDD patients (6) compared with the controls (16), aminoglycoside
      resistant strains being associated with zero episodes in SDD patients but with
      five in the control group.

PMID- 1348776
TI  - The housefly (Musca domestica) as a carrier of pathogenic microorganisms in a
      hospital environment.
AB  - Houseflies have long been regarded as potential carriers of microorganisms. Since
      pathogenic microorganisms are widespread in the hospital environment, there is
      abundant opportunity for flies to become contaminated and, in turn, to
      contaminate the patient environment. In the present study, an attempt was made to
      isolate and identify pathogenic bacteria, fungi and parasites from the housefly
      Musca domestica collected in the surgical ward of the All India Institute of
      Medical Sciences Hospital and also in a remote residential area located 5 km from
      the hospital. A total of 113 flies were collected: 65 from a surgical ward (test)
      and 48 from a residential area for comparison. Ten genera of bacteria were
      isolated from the test group of flies compared with nine from the control group.
      In primary isolations, it was observed that the load of bacteria carried by the
      test group of flies was significantly more (P less than 0.001) than for the
      control flies. Pseudomonas aeruginosa, Enterococcus faecalis and viridans
      streptococci were isolated only from the test flies. The isolation rate of
      Staphylococcus aureus was significantly higher (P less than 0.001) in test
      houseflies than in the control houseflies. There was no significant difference in
      isolation of parasitic ova and cysts from test and control houseflies. Candida
      spp. were isolated in almost equal numbers from both groups of houseflies, yet
      none of these was Candida albicans. Houseflies therefore may act as vectors of
      potentially pathogenic bacteria in a hospital environment.

PMID- 1348777
TI  - The use of the Body Mass Index in studies of abdominal wound infection.
AB  - Abdominal wound infection rates were significantly related to obesity, as
      measured by Body Mass Index, in two large clinical trials of prophylactic
      antibiotics in at-risk abdominal surgery. Obesity is a risk factor that should be
      taken into account in any study in which wound infection is an outcome measure.

PMID- 1348778
TI  - A novel methodology for the establishment of neuroblastoma cell lines from
      metastatic marrow. Expression of surface markers, neurofilaments, MDR-1 and myc
      proteins.
AB  - A methodology for rapid isolation of neuroblastoma (NB) cells from marrow with
      metastatic NB cells was developed using a cocktail of five antibodies and
      magnetic microspheres coated with secondary antibodies. Cells bound to
      microspheres were released by brief exposure to chymopapain, followed by repeated
      culture of released cells in serum supplemented DMEM medium and selection for
      adherent cells. Using this methodology, over 35 primary cell lines were obtained
      free of contaminating normal cells. Detailed analyses of over 14 cell lines
      revealed gross differences in cell phenotype, size, morphology development of
      neurite processes, and doubling time (40h-80 h). All cell lines expressed the 145
      kDa neurofilament (NF) and a few expressed the 200 kDa NF, with very little or no
      expression of the 68 kDa NF. DNA analyses revealed 80% near diploid cell lines.
      High expression of the MDR-1 protein was detected in 6/22 of the cell lines
      tested.

PMID- 1348779
TI  - Simultaneous assay for oxidative metabolism and adhesion of human neutrophils:
      evidence for correlations and dissociations of the two responses.
AB  - An assay method for the simultaneous evaluation of the oxidative metabolism and
      adherence of human neutrophils is described, together with certain specific
      applications. Incubations were performed in serum-coated microtiter plates, where
      oxidative metabolism was measured as O2- release and, after washing out the
      nonadherent cells, the adhesion was measured as activity of acid phosphatase.
      Three agonists tested in this system--opsonized zymosan, concanavalin A, and N
      formyl-methionyl-leucyl-phenylalanine--induced both activation of O2- release and
      cell adhesion, but the two functions had time course and dose dependence patterns
      that varied depending on the stimulant. Particularly with concanavalin A, O2-
      release and adhesion response were markedly dissociated; this lectin at low doses
      increased neutrophil adherence without triggering any O2- production, whereas at
      high doses it increased both O2- production and adherence. Anti-integrin
      monoclonal antibodies did not affect adhesion induced by low-dose concanavalin A
      but inhibited the adhesion induced by the other tested agonists. Adhesion and O2-
      production were also found to be differentially affected by the NADPH oxidase
      inhibitor diphenylene iodonium, the sulfhydryl reagent N-ethylmaleimide and the
      A2 agonist adenosine, indicating that these neutrophil responses have various
      transductional pathways that also depend on the type of stimulus.

PMID- 1348780
TI  - Monocyte adherence to fibronectin: role of CD11/CD18 integrins and relationship
      to other monocyte functions.
AB  - Adherence of monocytes to extracellular matrix components is critical for their
      accumulation at sites of infection. To gain insight into the factors that
      regulate monocyte recruitment, we have studied monocyte adherence with regard to
      the regulatory effects of bacterial lipopolysaccharide (LPS) and the mechanisms
      involved; moreover, we have contrasted the phenotypes of adherent and nonadherent
      cells. Our results show that only a minor subpopulation of monocytes (20-25%)
      adhere spontaneously to fibronectin and that LPS stimulated a threefold increase
      in the proportion of adherent cells. Basal adherence and LPS-stimulated adherence
      of monocytes to fibronectin were substantially mediated by CD11/CD18 integrins.
      Further studies revealed that spontaneously adherent monocytes were 14-fold more
      actively phagocytic, released 1.6-fold more superoxide anion, and contained 20
      fold more peroxidase activity than nonadherent cells, whereas LPS-adherent cells
      had an intermediate phenotype. These results indicate that LPS may enhance the
      accumulation of monocytes with an antimicrobial phenotype and thereby promote
      resolution of tissue infection.

PMID- 1348781
TI  - The glnA gene of the extremely thermophilic eubacterium Thermotoga maritima:
      cloning, primary structure, and expression in Escherichia coli.
AB  - The structural gene (glnA) encoding the glutamine synthetase (GS) of the
      extremely thermophilic eubacterium Thermotoga maritima has been cloned on a 6.0
      kb HindIII DNA fragment. Sequencing of the region containing the glnA gene (1444
      bp) showed an ORF encoding a polypeptide (439 residues) with an estimated mass of
      50,088 Da, which shared significant homology with the GSI sequences of other
      Bacteria (Escherichia coli, Bacillus subtilis) and Archaea (Pyrococcus woesei,
      Sulfolobus solfataricus). The T. maritima glnA gene was expressed in E. coli, as
      shown by the ability to complement a glnA lesion in the glutamine-auxotrophic
      strain ET8051. The recombinant GS has been partially characterized with respect
      to the temperature dependence of enzyme activity, molecular mass and mode of
      regulation. The molecular mass of the Thermotoga GS (590,000 Da), estimated by
      gel filtration, was compatible with a dodecameric composition for the holoenzyme,
      as expected for a glutamine synthetase of the GSI type. Comparison of the amino
      acid sequence of T. maritima GS with those from thermophilic and mesophilic micro
      organisms failed to detect any obvious features directly related to thermal
      stability.

PMID- 1348782
TI  - Application of screening and confirmatory assays for anti-HTLV-I/II in U.K.
      populations.
AB  - During an epidemiological study of a low risk U.K. population diverse screening
      and confirmatory assays for the detection of anti-HTLV-I/II were assessed. Sera
      from 2,900 antenatal patients were tested for anti-HTLV-I/II by gelatin particle
      agglutination assay (GPA). All reactive sera, and 133 randomly selected
      unreactive sera, were further tested by Abbott and DuPont ELISAs, "in house"
      competitive and IgG capture radioimmunoassays (RIAs), and Western blot (WB). Sera
      which reacted with any HTLV-I proteins by WB were tested by radio
      immunoprecipitation assays (RIPA). The two ELISAs detected all the GPA reactive
      specimens that were subsequently confirmed as anti-HTLV-I/II positive.
      Confirmation of positive screening results required the use of both WB and RIPA.
      Serological diagnosis of HTLV infection involves access to specialised assays
      that are not commercially available.

PMID- 1348784
TI  - "Hither neurology..." --meeting the challenge of neurological disability.
      Proceedings of a meeting. London, 24 October 1990.

PMID- 1348785
TI  - 22nd Annual Meeting of the American Pediatric Surgical Association. Part 1. Lake
      Buena Vista, Florida, May 15-18, 1991.

PMID- 1348783
TI  - Gerstmann-Straussler-Scheinker disease in an Alsatian family: clinical and
      genetic studies.
AB  - The clinical progression of Gerstmann-Straussler-Scheinker disease in a family of
      Alsatian origin is reported. The age of onset and the duration of evolution were
      variable. The clinical picture became more complex over the generations: in the
      first generations, isolated dementia and in later generations a triad of
      pyramidal, pseudobulbar syndromes and dementia associated with spinal cord and
      cerebellar features. Prion gene analysis showed that four surviving patients
      carry double missense changes at codons 117 and 129, identical to those found in
      one case at necropsy and 10 other healthy members of the family. The missense
      changes were not found in 100 controls. No member of the family had modification
      of condons 102, 178, or 200. The lod score suggests linkage between the missense
      change at codon 117 and Gerstmann-Straussler-Scheinker disease in this family.

PMID- 1348786
TI  - Laparoscopy for the impalpable testes: experience with 53 testes.
AB  - Impalpable testes constitute approximately 20% of most series of undescended
      testes. From January 1986 to March 1991, we performed laparoscopies on 53
      patients with impalpable testes. Thirty-two of them were found to have normal
      vasa and vessels entering each internal ring on the side in question. Of these,
      14 were found to have "vanishing testes" at exploration, 12 others underwent
      successful orchiopexy, and the remaining 6 had excisional biopsies of fibrotic
      testicular remnants. Five patients had no visible vessels and a sixth had a blind
      ending vas and vessels adjacent to the internal ring; in these cases no further
      investigations were deemed necessary. Fifteen patients were found to have
      abdominal testes and underwent high testicular vessel ligation and division at
      the time of the laparoscopy; 14 of them have undergone staged orchiopexy 6 months
      after laparoscopy and one is scheduled for this procedure. A 3-month follow-up of
      those who had orchiopexy showed excellent results in 10 patients and poor results
      in 3, all of whom had small testes that were unimproved or worse following vessel
      ligation. Four boys were spared operations as a result of findings at
      laparoscopy. Early in the series there was one failed laparoscopy, but it was
      successfully completed later. the procedure, but it was successfully treated with
      antibiotics. There were no other complications. Laparoscopy is a safe procedure
      that allows accurate diagnosis and may prevent additional intervention in the
      treatment of the absent testes. It facilitates the locating of the impalpable
      testis and the planning and timing of subsequent orchiopexy. We believe that
      laparoscopy is the preferred procedure in the management of impalpable testes.

PMID- 1348787
TI  - Short-acting beta-adrenergic blockade and the fetus. A case report.
AB  - An infant was born to a woman who received intravenous esmolol for intrapartum
      supraventricular tachyarrhythmia. Despite the very short acting and cardio
      selective beta-1 adrenergic blockade induced by that agent, neonatal effects can
      occur up to 48 hours after delivery.

PMID- 1348788
TI  - From the Centers for Disease Control. Recommendations for prophylaxis against
      Pneumocystis carinii pneumonia for adults and adolescents infected with HIV.

PMID- 1348790
TI  - Neural tube rupture as a cause of neural tube defects.

PMID- 1348789
TI  - Prevalence of substance use among US physicians.
AB  - OBJECTIVE: To estimate the prevalence of substance use among US physicians.
      DESIGN: A mailed, anonymous, self-report survey that assessed use of 13
      substances and permitted comparison with results of the National Household Survey
      on Drug Abuse. Rates of physician substance use were weighted to provide national
      prevalence estimates. PARTICIPANTS: A national sample of 9600 physicians,
      stratified by specialty and career stage, and randomly selected from the American
      Medical Association master file. The response rate after three mailings was 59%.
      Demographic characteristics of respondents closely reflected those of the US
      physician population. MAIN OUTCOME MEASURES: Subjects' self-reported use of 13
      substances in their lifetime, the past year, and the past month; reasons for use;
      self-admitted substance abuse or dependence; and whether treatment was received.
      For controlled prescription substances, respondents were asked to report only use
      "not prescribed by another physician for a legitimate medical or psychiatric
      condition." RESULTS: Physicians were less likely to have used cigarettes and
      illicit substances, such as marijuana, cocaine, and heroin, in the past year than
      their age and gender counterparts in the National Household Survey on Drug Abuse.
      They were more likely to have used alcohol and two types of prescription
      medications--minor opiates and benzodiazepine tranquilizers. Prescription
      substances were used primarily for self-treatment, whereas illicit substances and
      alcohol were used primarily for recreation. Current daily use of illicit or
      controlled substances was rare. CONCLUSIONS: Although physicians were as likely
      to have experimented with illicit substances in their lifetime as their age and
      gender peers in society, they were far less likely to be current users of illicit
      substances. The higher prevalence of alcohol use among respondents may be more a
      characteristic of their socioeconomic class than of their profession. A unique
      concern for physicians, however, is their high rate of self-treatment with
      controlled medications--a practice that could increase their risk of drug abuse
      or dependence. Uniform national guidelines are needed to sensitize medical
      students and physicians to the dangers of self-treatment with controlled
      prescription substances.

PMID- 1348791
TI  - Mean platelet volume and myocardial infarction.

PMID- 1348792
TI  - Low serum cholesterol and suicide.

PMID- 1348793
TI  - Pyramidal tract signs and Parkinson's disease.

PMID- 1348794
TI  - Low serum cholesterol and suicide.

PMID- 1348795
TI  - Homozygosity mapping and Werner's syndrome.

PMID- 1348796
TI  - Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma.
AB  - Aflatoxins have long been suspected to be human hepatic carcinogens but no direct
      study was feasible until assays to measure individual aflatoxin exposure became
      available. We have used assays for urinary aflatoxin B1, its metabolites AFP1 and
      AFM1, and DNA-adducts (AFB1-N7-Gua) to assess the relation between aflatoxin
      exposure and liver cancer, as part of an ongoing prospective study of 18,244
      middle-aged men in Shanghai, People's Republic of China. After 35,299 person
      years of follow-up, 22 cases of liver cancer had been identified. For each case,
      5 or 10 controls were randomly selected from cohort members without liver cancer
      on the date the disorder was diagnosed in the case and matched to within 1 year
      for age, within 1 month for sample collection, and for neighbourhood of
      residence. Subjects with liver cancer were more likely than were controls to have
      detectable concentrations of any of the aflatoxin metabolites (relative risk 2.4,
      95% confidence interval 1.0-5.9). The highest relative risk was for aflatoxin P1
      (6.2, 1.8-21.5). In an analysis adjusting for the effects of hepatitis B surface
      antigen seropositivity, level of education, cigarette smoking, and alcohol
      consumption, the relative risk for the presence of aflatoxin metabolites was 3.8
      (1.2-12.2). There was a strong interaction between serological markers of chronic
      hepatitis B infection and aflatoxin exposure in liver-cancer risk. Reduction of
      aflatoxin exposure may be a useful intermediate goal in prevention of liver
      cancer, since the benefits of wide-scale hepatitis B vaccination will not be
      apparent for many years.

PMID- 1348797
TI  - Prophylactic ciprofloxacin for catheter-associated urinary-tract infection.
AB  - Patients receiving antibiotics during bladder drainage have a lower incidence of
      urinary-tract infections compared with similar patients not on antibiotics.
      However, antibiotic prophylaxis in patients with a urinary catheter is opposed
      because of the fear of inducing resistant bacterial strains. We have done a
      double-blind, placebo-controlled trial of prophylactic ciprofloxacin in selected
      groups of surgical patients who had postoperative bladder drainage scheduled to
      last for 3 to 14 days. Patients were randomly assigned to receive placebo (n =
      61), 250 mg ciprofloxacin per day (n = 59), or 500 mg ciprofloxacin twice daily
      (n = 64) from postoperative day 2 until catheter removal. 75% of placebo patients
      were bacteriuric at catheter removal compared with 16% of ciprofloxacin-treated
      patients (relative risk [RR] [95% CI] 4.7 [3.0-7.4]). The prevalence of pyuria
      among placebo patients increased from 11% to 42% while the catheter was in place;
      by contrast, the rate of pyuria was 11% or less in patients receiving
      ciprofloxacin (RR 4.0 [2.1-7.3]). 20% of placebo patients had symptomatic urinary
      tract infections, including 3 with septicaemia, compared with 5% of the
      ciprofloxacin groups (RR 4.0 [1.6-10.2]). Bacteria isolated from urines of
      placebo patients at catheter removal were mostly species of enterobacteriaceae
      (37%), staphylococci (26%), and Enterococcus faecalis (20%), whereas species
      isolated from urines of ciprofloxacin patients were virtually all gram-positive.
      Ciprofloxacin-resistant mutants of normally sensitive gram-negative bacteria were
      not observed. Ciprofloxacin prophylaxis is effective and safe in the prevention
      of catheter-associated urinary tract infection and related morbidity in selected
      groups of patients requiring 3 to 14 days of bladder drainage.

PMID- 1348798
TI  - Hepatitis B virus and apparent fulminant non-A, non-B hepatitis.
AB  - While there is evidence that hepatitis C virus (HCV) does not cause fulminant non
      A, non-B hepatitis, the causal agent remains unknown. To evaluate the role of
      hepatitis B virus (HBV) in this disease, we used a two-step polymerase chain
      reaction (PCR) to amplify the surface and core regions of HBV DNA in serum and
      liver samples taken prospectively from twenty-six patients (mean age 36 years,
      range 1 to 64) with acute hepatic failure undergoing liver transplantation. HBV
      DNA was absent from the serum of all patients before transplantation. Seventeen
      patients were diagnosed as having non-A, non-B hepatitis because they lacked
      serological evidence of hepatitis A virus or HBV infection. Liver samples were
      taken from twelve of these patients, and six samples were positive for HBV DNA.
      By contrast HBV DNA was not detected in liver from three patients with acute
      liver failure caused by hepatitis A or toxins. HCV RNA was not found in
      pretransplant samples by PCR. Four of the six patients with detectable HBV DNA in
      liver and presumptive non-A, non-B hepatitis had detectable HBV DNA in serum
      after transplantation. One additional patient who did not donate pretransplant
      liver had HBV DNA in a post-transplant serum sample. Thus, HBV DNA was present
      before or after transplantation in seven of seventeen patients with apparent non
      A, non-B hepatitis. Three of five patients with detectable post-transplant serum
      HBV DNA were serologically positive for HBV surface antigen. These findings
      indicate that HBV may be a common cause of fulminant hepatic failure in patients
      lacking serological evidence of HBV infection.

PMID- 1348799
TI  - Subcurative chemotherapy and fatal post-treatment reactive encephalopathies in
      African trypanosomiasis.
AB  - The treatment of late-stage African sleeping sickness in man is often complicated
      by a post-treatment reactive encephalopathy. The bases of this pathological
      reaction was investigated in a mouse model of African trypanosomiasis.
      Subcurative treatment with diminazene aceturate, which did not clear parasites
      from the central nervous system, resulted in a post-treatment meningoencephalitis
      similar to that seen in man. By contrast, a curative regimen of
      melaminylthioarsenite and 5-nitroimidazole, which cleared parasites from the
      central nervous system, did not cause any pathological reaction in the mice. This
      result indicates that subcurative treatment leads to the development of the post
      treatment encephalopathy. Evidence that this may also be the case in man was
      provided by the detection of trypanosome DNA with the polymerase chain reaction
      in the brains of 9 patients who had died as the result of a post-treatment
      reaction. Our findings suggest that more aggressive treatment regimens, which
      ensure the elimination of trypanosomes from the central nervous system, may
      prevent post-treatment reactions in patients.

PMID- 1348800
TI  - Human papillomavirus type 16 in cervical smears as predictor of high-grade
      cervical intraepithelial neoplasia [corrected].
AB  - The management of women with mild to moderately dyskaryotic cervical smears would
      benefit from a non-invasive test that predicts which women have high-grade
      cervical intraepithelial neoplasia. Detection of human papillomavirus type 16
      (HPV16) DNA in cervical smears may be such a test. With the polymerase chain
      reaction (PCR), we estimated the amount of HPV16 DNA in cervical smears from 85
      women referred for colposcopy because of abnormal cytology. An intermediate or
      high amount of HPV16 DNA predicted the presence of high-grade cervical
      intraepithelial neoplasia in a subsequent biopsy in almost 90% of patients
      irrespective of the cytological grade of the referral smear. This technique may
      allow early identification of those women with low-grade cytological
      abnormalities who have high-grade underlying cervical disease.

PMID- 1348801
TI  - Oxygen restriction and retinopathy of prematurity.

PMID- 1348802
TI  - Digit sucking.

PMID- 1348803
TI  - Cervical cancer screening: quest for automation.

PMID- 1348804
TI  - Dead or alive.

PMID- 1348805
TI  - Controlled trial of endoscopic injection treatment for bleeding from peptic
      ulcers with visible vessels.
AB  - Controlled trials have shown that bleeding peptic ulcers can be successfully
      treated by endoscopy and injection of adrenaline, with or without sclerosant.
      However, these trials have been done in major research centres, and endoscopic
      treatment of upper gastrointestinal bleeding has not yet become routine in
      general hospitals. We have done a prospective, randomised, controlled trial of
      injection treatment for bleeding peptic ulcers in a district general hospital.
      Between April, 1989, and June, 1991, all patients with acute upper
      gastrointestinal bleeding (n = 555) underwent endoscopy by an experienced
      endoscopist within 24 h of admission. 98 patients were found to have an ulcer
      with a visible vessel, of whom 93 were randomised to injection (n = 48) or
      standard treatment alone (n = 45). Injection treatment consisted of 1-2 ml of 1
      in 10,000 adrenaline injected at four to six sites around the ulcer. Adrenaline
      and 5% ethanolamine oleate (1-2 ml) were then injected directly into the vessel.
      The medical team managing the patient was unaware of the endoscopic treatment
      given. The two groups were similar for age, initial haemoglobin concentration,
      shock, and ulcer site. Rebleeding (injected 8 [16.7%] vs control 21 [46.7%], p =
      0.011) was significantly reduced in treated patients. The treated group also had
      lower mortality (4 [8.3%] vs 9 [20%]), requirement for surgery (4 [8.3%] vs 8
      [17.8%]), and mean blood-transfusion requirement (5 vs 7.5 units). Endoscopic
      injection treatment in our patients significantly reduced rebleeding rate and may
      have other benefits. This cheap and widely applicable treatment can be used
      routinely in the management of patients with bleeding peptic ulcers who are at
      high risk of rebleeding.

PMID- 1348806
TI  - Clinical study of the lactational amenorrhoea method for family planning.
AB  - The effect of breastfeeding on fertility is well known; however, its use as a
      method of family planning was, until recently, untested. In 1988, the Bellagio
      Consensus Conference proposed guidelines that became the basis for a method of
      family planning called the lactational amenorrhoea method (LAM). The principle of
      LAM is that a woman who continues to fully or nearly fully breastfeed her infant
      and who remains amenorrhoeic during the first 6 months postpartum is protected
      from pregnancy during that time. We have assessed this method in the context of a
      breastfeeding support intervention study of 422 middle-class women in urban
      Santiago, Chile. The cumulative 6-month life-table pregnancy rate was 0.45% among
      women who relied on LAM as their only family planning method (1 woman pregnant in
      month 6). The findings indicate that LAM, with its high acceptance and efficacy,
      is a viable method of family planning and can safely serve as an introductory
      method for breastfeeding women.

PMID- 1348807
TI  - Cutaneous malignant melanoma, Scotland, 1979-89. The Scottish Melanoma Group.
AB  - The Scottish Melanoma Group (SMG) was established in 1979 to assess mortality
      from and incidence, features, pathological data, and management of cutaneous
      malignant melanoma in Scotland. Incidence during the first five years and five
      year survival have already been reported. We now have data about incidence and
      mortality over eleven years in relation to anatomical site and pathological
      types. From 1979 to 1989, 1354 male and 2459 female patients with primary
      cutaneous malignant melanomas were first diagnosed in Scottish residents. The
      incidence rate per 100,000 population per year has increased from 3.4 in 1979 to
      7.1 in 1989 for men, and from 6.6 to 10.4 for women. The overall increase over
      eleven years is 82% (7.4% per year). The greatest rates of increase are seen in
      lesions of the superficial spreading histogenetic type, arising on the female leg
      and the male trunk. Following public education programmes started in 1985, the
      proportion of all melanomas less than 1.5 mm thick has shown a sustained and
      significant increase. Mortality data for 1661 patients for whom a minimum of five
      year follow-up is available shows five-year survival of 71.6% overall (77.6% for
      women, 58.7% for men). The survival advantage for women persists when appropriate
      statistical adjustment is made for thickness, ulceration, and histogenetic type.
      These data are useful in designing public education programmes aimed at both
      primary and secondary prevention of melanoma and in auditing changes in trends
      that might result from such education.

PMID- 1348808
TI  - Embryonal germ-layer antigens: target for autoimmunity.
AB  - Histopathological analysis of some systemic autoimmune diseases and syndromes led
      us to the conclusion that the common feature of the organs involved might be
      their embryonal origin. We suggest that organs derived from the same germ layer
      express common germ-layer-specific antigens. Such antigens could serve as target
      antigens for the autoimmune response.

PMID- 1348809
TI  - Double-edged role of endogenous nitric oxide.

PMID- 1348810
TI  - Coronary heart disease in women.

PMID- 1348811
TI  - Coronary heart disease in women.

PMID- 1348812
TI  - Coronary heart disease and dietary factors.

PMID- 1348813
TI  - Atypical treatments for schizophrenia.

PMID- 1348814
TI  - Penicillin-resistant pneumococci and community-acquired pneumonia.

PMID- 1348815
TI  - Cholera diagnosed in clinical laboratory by DNA hybridisation.

PMID- 1348816
TI  - Hepatitis C virus and mixed cryoglobulinaemias.

PMID- 1348817
TI  - Hepatitis C virus and Sjogren's syndrome.

PMID- 1348818
TI  - C1-inhibitor concentrate for sepsis-related capillary leak syndrome.

PMID- 1348819
TI  - Sex of children born to women with cystic fibrosis.

PMID- 1348820
TI  - Respiratory disease in very-low-birthweight infants.

PMID- 1348821
TI  - Pertussis in infants.

PMID- 1348822
TI  - Possible association of erythema multiforme with acamprosate.

PMID- 1348823
TI  - Ewing's sarcoma and its neural differentiation.

PMID- 1348824
TI  - Myeloma therapy.

PMID- 1348825
TI  - Chlamydial and rickettsial transmission through tick bite in children.

PMID- 1348826
TI  - Acute paralytic disease.

PMID- 1348827
TI  - Urapidil and the bladder.

PMID- 1348828
TI  - Prevention vs cure in developing countries.

PMID- 1348829
TI  - Prevention vs cure in developing countries.

PMID- 1348830
TI  - Surgical careers and female students.

PMID- 1348831
TI  - Reliability of population and prevalence estimates.

PMID- 1348832
TI  - Drug aid for the former Soviet Union.

PMID- 1348833
TI  - Abortion across countries.

PMID- 1348834
TI  - Assessment of arteriovenous haemodialysis fistulas.

PMID- 1348835
TI  - Peripheral intravenous nutrition.

PMID- 1348836
TI  - Seizure induction and transcranial magnetic stimulation.

PMID- 1348837
TI  - Unusual non-toxigenic Corynebacterium diphtheriae in homosexual men.

PMID- 1348838
TI  - p24 antigen and HIV screening.

PMID- 1348839
TI  - Retroperitoneal germ cell neoplasm: MR and CT.
AB  - A case of germ cell neoplasm in an undescended retroperitoneal testicle is
      reported. CT revealed a large mass most consistent with a chronic hematoma. MRI
      demonstrated findings typical for neoplasm, and this was confirmed on biopsy.

PMID- 1348840
TI  - Ross River virus: an Australian export?

PMID- 1348841
TI  - Risk factors for hypertension in Kimberley aborigines.
AB  - OBJECTIVE: To determine physical, biochemical and lifestyle factors associated
      with high blood pressure among Aborigines in the Kimberley region. DESIGN: Blood
      pressure and electrocardiographic (ECG) abnormalities in an age and sex
      stratified random sample of the Aboriginal population were related to other
      observations and measurements made at the same time specifically for the purpose
      of these comparisons. SETTING: A field study in which subjects were interviewed
      and measurements made mostly in community clinics. PARTICIPANTS: All 249 men and
      241 women from the prevalence study were included although only complete data
      sets for the various comparisons were analysed. INTERVENTIONS: A sample of venous
      blood was obtained in addition to physical measurements and information at
      interview. MAIN OUTCOME MEASURES: Statistical analysis of the relationships
      between blood pressure or hypertension and alcohol consumption, plasma gamma
      glutamyl transpeptidase (GGT) activity, use of tobacco, body mass index (BMI,
      kg/m2) and non-fasted plasma cholesterol level. Hypertension was defined as
      systolic blood pressure of 160 mmHg or greater or diastolic blood pressure of 95
      mmHg or greater. RESULTS: High blood pressure in Aboriginal men below 30 years
      was associated both with current drinking status and with circulating GGT level.
      There was a positive association of diastolic hypertension with consumption of
      alcohol in middle aged men (30 to 49 years) and in older women. Drinking was
      highly prevalent among men, especially below 30 years, but was less prevalent
      among women. Both systolic and diastolic blood pressure were positively related
      to BMI across the population but obesity (BMI greater than or equal to 30 kg/m2)
      was highly prevalent only among middle-aged women. Both systolic and diastolic
      blood pressure were positively and strongly related to plasma cholesterol level
      independently of the latter's relationship to age and BMI. CONCLUSION: The high
      prevalence of drinking among Aboriginal men and of obesity among Aboriginal women
      involves a risk of hypertension. The association between plasma cholesterol and
      blood pressure in Aboriginal men and women may be relevant to the demonstrated
      link between systolic hypertension and ischaemic heart disease.

PMID- 1348842
TI  - The health of indigenous peoples.

PMID- 1348843
TI  - Recommendations for prophylaxis against Pneumocystis carinii pneumonia for adults
      and adolescents infected with human immunodeficiency virus.
AB  - In 1989, the United States Public Health Service convened a Task Force of experts
      to consider the expanding knowledge base about prevention of Pneumocystis carinii
      pneumonia (PCP) among adults and adolescents (greater than or equal to 13 years
      of age) with human immunodeficiency virus (HIV) infection. This Task Force
      concluded that the morbidity, mortality, and cost due to PCP could be
      substantially reduced by appropriate use of antipneumocystis prophylaxis in
      subgroups of HIV-infected patients known to be at high risk, and developed
      recommendations for the administration of prophylactic regimens (1). The
      recommendations state that CD4+ T-lymphocyte counts should be monitored
      prospectively at 3- to 6-month intervals and prophylaxis should be instituted
      when patients become immunologically susceptible to PCP. Susceptibility was
      defined by a CD4+ T-lymphocyte count less than 200 cells/microliters or less than
      20% of total circulating lymphocytes, or the occurrence of a previous episode of
      PCP. The goal of this approach was to reduce the frequency both of initial
      episodes of PCP (primary prophylaxis) and of relapses or recurrences (secondary
      prophylaxis). Either oral trimethoprim-sulfamethoxazole (TMP-SMX) or aerosol
      pentamidine was recommended for prophylaxis, but because direct comparative data
      were lacking, neither regimen was endorsed as "preferred." Since the
      recommendations were issued in 1989, additional information has become available
      about the efficacy and safety of aerosol pentamidine and oral TMP-SMX. A trial
      sponsored by the National Institute of Allergy and Infectious Diseases AIDS
      Clinical Trials Group compared these two regimens in a prospective randomized
      study; in August 1991, this study was terminated by an independent data and
      safety monitoring board because statistically significantly fewer recurrences of
      PCP were observed in the oral TMP-SMX group than in the aerosol pentamidine group
      (2). On the basis of this finding and other studies assessing PCP prophylaxis,
      the Task Force was reconvened on October 5, 1991. This report contains the
      revised recommendations issued by the Task Force.

PMID- 1348844
TI  - [Encephalitis. Recent clinical, diagnostic and therapeutic aspects].
AB  - The subjects of this paper are mainly the encephalitis of viral origin and in
      addition 3 types of non-viral encephalitis of practical importance. A review is
      given on the current diagnostic possibilities including; clinical criteria;
      examination of the cerebrospinal fluid; neuroradiology and; etiological
      investigation by means of direct identification of the microbes in the
      cerebrospinal fluid or by measuring intrathecally produced antibodies. After some
      general statements concerning treatment the specifically treatable encephalitis
      caused by Herpes simplex virus, Mycoplasma pneumoniae, Borrelia burgdorferi and
      Toxoplasma gondii are discussed in more detail.

PMID- 1348845
TI  - Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects
      and patients with diabetes mellitus.
AB  - BACKGROUND: Glucagon-like peptide-1 (7-36) amide (glucagon-like insulinotropic
      peptide, or GLIP) is a gastrointestinal peptide that potentiates the release of
      insulin in physiologic concentrations. Its effects in patients with diabetes
      mellitus are not known. METHODS: We compared the effect of an infusion of GLIP
      that raised plasma concentrations of GLIP twofold with the effect of an infusion
      of saline, on the meal-related release of insulin, glucagon, and somatostatin in
      eight normal subjects, nine obese patients with non-insulin-dependent diabetes
      mellitus (NIDDM), and eight patients with insulin-dependent diabetes mellitus
      (IDDM). The blood glucose concentrations in the patients with diabetes were
      controlled by a closed-loop insulin-infusion system (artificial pancreas) during
      the infusion of each agent, allowing measurement of the meal-related requirement
      for exogenous insulin. In the patients with IDDM, normoglycemic-clamp studies
      were performed during the infusions of GLIP and saline to determine the effect of
      GLIP on insulin sensitivity. RESULTS: In the normal subjects, the infusion of
      GLIP significantly lowered the meal-related increases in the blood glucose
      concentration (P less than 0.01) and the plasma concentrations of insulin and
      glucagon (P less than 0.05 for both comparisons). The insulinogenic index (the
      ratio of insulin to glucose) increased almost 10-fold, indicating that GLIP had
      an insulinotropic effect. In the patients with NIDDM, the infusion of GLIP
      reduced the mean (+/- SE) calculated isoglycemic meal-related requirement for
      insulin from 17.4 +/- 2.8 to 2.0 +/- 0.5 U (P less than 0.001), so that the
      integrated area under the curve for plasma free insulin was decreased (P less
      than 0.05) in spite of the stimulation of insulin release. In the patients with
      IDDM, the GLIP infusion decreased the calculated isoglycemic meal-related insulin
      requirement from 9.4 +/- 1.5 to 4.7 +/- 1.4 U. The peptide decreased glucagon and
      somatostatin release in both groups of patients. In the normoglycemic-clamp
      studies in the patients with IDDM, the GLIP infusion significantly increased
      glucose utilization (saline vs. GLIP, 7.2 +/- 0.5 vs. 8.6 +/- 0.4 mg per kilogram
      of body weight per minute; P less than 0.01). CONCLUSIONS: GLIP has an
      antidiabetogenic effect, and it may therefore be useful in the treatment of
      patients with NIDDM:

PMID- 1348846
TI  - Usefulness of the assessment of urinary enzymes and microproteins in monitoring
      ciclosporin nephrotoxicity.
AB  - The clinical usefulness of serial assays of urinary N-acetyl-beta-D-
      glucosaminidase (NAG), gamma-glutamyltransferase (GGT) and beta 2-microglobulin
      (beta 2M) were tested to evaluate and follow up the nephrotoxicity resulting from
      the prolonged administration of ciclosporin (CS). Three groups of patients were
      studied for 18 months: group A: functioning renal transplant patients (n = 13) on
      maintenance therapy from 12-31 months with CS and prednisone; group B:
      functioning renal transplant patients (n = 11) treated with prednisone and
      azathioprine; group C: patients (n = 10) affected by autoimmune steroid
      unsensitive uveitis, free from previous renal disorder and treated with CS (for 8
      16 months) at progressively decreasing doses. In groups A and B, the urinary
      enzymes and beta 2M underwent overlapping increases, so that these parameters
      cannot be considered reliable indices of CS-induced nephrotoxicity. This is due
      to the fact that transplanted kidneys are already altered by concomitant or
      preexisting affections, or by persistent immunologic injury. Conversely, in
      patients with uveitis, the serial assays of such urinary parameters prove to be
      quite reliable to evidence clinically yet unrecognizable kidney involvement due
      to prolonged CS administration. High enzymuria has been shown to be an earlier
      marker of nephrotoxicity only in nephropathy-free patients; on the other hand,
      the regression of elevated beta 2Muria into normal ranges indicates complete
      tubule cell recovery.

PMID- 1348847
TI  - Dopa accumulates in the hypothalamic-hypophysial portal vessels and is taken into
      the anterior pituitary of NSD-1015-treated rodents.
AB  - DOPA was measured in the anterior pituitary and hypothalamic-hypophysial portal
      blood after treatment with NSD-1015, a DOPA decarboxylase inhibitor. NSD-1015
      caused DOPA to accumulate in the anterior pituitary of mice and rats, and
      increased DOPA in the hypothalamic-hypophysial portal blood of rat. Serum
      prolactin was also increased. Interruption of the anterior pituitary blood supply
      from the hypothalamic-hypophysial system by cannulation of the entire pituitary
      stalk eliminated the NSD-1015-induced DOPA accumulation in the rat pituitary. We
      conclude that DOPA can be taken into the anterior pituitary from the portal blood
      of NSD-1015-treated rodents and that the anterior pituitary lacks tyrosine
      hydroxylase activity in both mice and rats.

PMID- 1348848
TI  - Central mechanisms subserving the impaired growth hormone secretion induced by
      persistent blockade of NMDA receptors in immature male rats.
AB  - Recently, we have reported in immature female rats that short-term blockade of
      glutamate receptors of the N-methyl-D-aspartic acid (NMDA) subtype by the
      noncompetitive antagonist MK-801 induced a reduction of growth rate, basal and
      stimulated growth hormone (GH) release and plasma somatomedin C levels. In the
      present study, we investigated in immature male rats the mechanism(s) through
      which agonists and antagonists of glutamate receptors affect GH secretion. In 21
      day-old male rats, administration of MK-801 (0.2 mg/kg i.p.b.i.d.) for 10 days
      induced a significant impairment of growth rate, which was unrelated to a
      significant reduction of food intake. GH secretion from anterior pituitary
      fragments of MK-801-treated rats was not significantly reduced under basal
      conditions but was significantly less under stimulation by 40 mM K+. Incubation
      of dispersed pituitary cells of 31-day-old rats with N-methyl-aspartic acid (1
      and 100 microM), alone or associated with MK-801 (1 microM) did not change GH
      secretion. Semi quantitative densitometric analysis of hypothalami of MK-801
      treated rats evidenced a clearcut decrease in the intensity of GHRH-like immuno
      reactivity (LI) staining in the median eminence (ME), whereas no difference was
      observed in the ME-somatostatin (SS)-LI. Finally, GHRH mRNA but not SS-mRNA,
      evaluated by slot-blot hybridization, was reduced in the hypothalamus of MK-801
      treated rats. These and our previous data would demonstrate that NMDA glutamate
      receptors play an important role in the neuroendocrine control of GH secretion in
      the rat, and suggest an action mediated by GHRH-secreting neurons.

PMID- 1348849
TI  - The effect of benzodiazepines on the fetus and the newborn.
AB  - The effect of the maternal use of benzodiazepines (BZD) on the fetus and the
      newborn infant has been studied in a representative series of 17 newborn infants
      (BZD group). The pregnancy and the perinatal period were characterized by 20
      items. On the 2nd day of life, a neurologic investigation was performed and
      comprised a total of 38 items, subgrouped into items of reflexes/reactions,
      tonus, and other symptoms and signs. An optimum finding for each item was
      selected. The results were compared with a group of 21 newborns fetally exposed
      to psychotropic drugs other than BZD (drug group) and a reference group of 29
      newborns with no known fetal exposure to drugs. Infants in the BZD group had a
      lower birth weight for birth length, as compared to both the drug group and the
      reference group. Significant differences in frequency of pre- and perinatal
      complications and in neuro-behavior between the BZD group and the reference group
      were found in all groups of items. We conclude that the use of BZD during
      pregnancy is associated with impaired intrauterine growth and an increased
      frequency of pre- and perinatal events. It affects the newborn infant
      neurologically mainly in the form of intoxication and withdrawal symptoms.

PMID- 1348850
TI  - Mononeuritis multiplex in a child with cutaneous polyarteritis.
AB  - A 14-year-old boy presented with a febrile illness associated with arthritis.
      Shortly later he developed mononeuritis multiplex. After certain typical skin
      lesions had developed after two months, the diagnosis cutaneous polyarteritis
      could be made. The diagnostic features of this benign disease, which may involve
      peripheral nerves, are discussed.

PMID- 1348851
TI  - Prion protein mutation at codon 102 in an Italian family with Gerstmann
      Straussler-Scheinker syndrome.
AB  - We present the first family from Italy with the Gerstmann-Straussler-Scheinker
      syndrome (GSS) and a substitution of leucine for proline at codon 102 of the
      prion protein gene. This mutation is associated with the ataxic form of GSS in a
      number of reported families. The clinical presentation of our family includes
      amyotrophic changes in some affected family members in addition to ataxia.

PMID- 1348852
TI  - Discordance of the T-cell receptor alpha-chain gene in familial multiple
      sclerosis.
AB  - We studied restriction fragment length polymorphisms of the T-cell receptor alpha
      chain (TCR alpha) gene in DNA obtained from 99 individuals of 14 multiplex
      families with multiple sclerosis (MS). Thirty-four family members had definite MS
      and two had probable MS. Six normal family members had abnormal cranial MRIs.
      Linkage analysis utilized constructed haplotypes of EcoRV, Sst I, and Taq I
      polymorphisms. With penetrance values from 0.1 to 0.7, and scoring the normal
      individuals with abnormal MRIs as either unknown or affected, LOD scores were
      between -3.16 and -7.95 for the autosomal dominant model. For the autosomal
      recessive model with a penetrance range from 0.1 to 1, the LOD scores ranged from
      -6.77 to -23.08. These findings do not support a direct role of TCR alpha in the
      inheritance of MS.

PMID- 1348854
TI  - Intrusive injuries to the dentition.

PMID- 1348853
TI  - [Takayasu disease in the genesis of cerebrovascular insufficiency. Description
      and considerations of a clinical case].
AB  - The authors in explaining their limited clinical experience relative to one
      single case, describe the peculiarity of Takayasu's disease and its rare
      incidence in western populations. The case under observation because of its
      peculiar rarity had been underestimated and treated in a completely inappropriate
      manner. Important instrument in its diagnosis is the High Resolution echography
      which in determining the diagnosis favors and speeds up the diagnostic
      therapeutic iter.

PMID- 1348855
TI  - Cloning and characterization of the mouse neu promoter.
AB  - We have isolated a genomic clone containing the mouse neu gene. The 5' end of the
      mouse neu gene was localized by Southern analysis, subcloned and characterized.
      DNA sequence analysis revealed that the promoter region is 67% G+C-rich and lacks
      a TATA box, although a CAAT box is present. By sequence comparison, we identified
      several consensus recognition sequences for general transcription factors such as
      Sp1, E4TF1, AP2, OTF-1 and GCF, as well as recognition sequences for RVF, E1A and
      GTG, which have recently been identified in the rat neu promoter. Functional
      promoter activity was demonstrated by the ability of the promoter to drive
      transcription of the bacterial chloramphenicol acetyltransferase gene. Using a
      series of 5'-end deletion mutants, we have identified multiple positive and
      negative cis-acting elements that regulate mouse neu gene transcription.

PMID- 1348856
TI  - [Value of the prifinium bromide test in hyperactive bladder].

PMID- 1348857
TI  - Neisseria gonorrhoeae PilC expression provides a selective mechanism for
      structural diversity of pili.
AB  - Pili of Neisseria gonorrhoeae undergo both phase and structural variation. Phase
      variation of gonococcal pili can be caused by a RecA-independent on/off switch in
      PilC, a protein involved in pilus biogenesis. We show here that spontaneous
      nonpiliated PilC- derivatives as well as PilC- insertional mutants have also
      acquired sequence alterations in pilE relative to the pilE gene of the piliated
      MS11mk(P+)-u parent, so that the pilin produced is processed to soluble S-pilin
      and can be released into the medium. It is proposed that pilin alterations are
      selected for in PilC- bacteria if the parental nonassembled pilin is toxic to the
      cells--i.e., is not degradable to S-pilin at rates sufficient to allow viability
      of the cells. Toxicity is indicated by the extreme instability of certain
      unassembled pilin sequences and by the low frequency of nonpiliated, pilin+, PilC
      variants that emerge from piliated recA- cells. The presence of a point mutation
      changing leucine-39 to phenylalanine at the cleavage site for S-pilin in one
      nonpiliated, PilC-, recA- variant relative to its piliated parent is a further
      argument for a selective mechanism of structural diversity of the gonococcal
      pilin.

PMID- 1348858
TI  - RHS2, a POU domain-containing gene, and its expression in developing and adult
      rat.
AB  - Gene expression within the central nervous system is regulated by complex
      interactions of DNA-binding proteins, among which are the POU domain-containing
      proteins, which are distantly related to homeobox proteins. These POU domain
      containing proteins have been implicated in control of transcription and
      replication within the central nervous system. We used degenerate primers with
      the PCR to isolate another POU domain-containing cDNA, RHS2, from hypothalamic
      RNA. Isolation of a putative full-length cDNA was accomplished by using serial
      dilutions of a hypothalamic cDNA library grown on solid medium. This member of
      the class III POU family is expressed in rats from embryonic day 11.5 into
      adulthood, being especially prominent in the brain. We performed double-labeling
      hybridization histochemistry and determined that RHS2 is coexpressed with a
      variety of neuropeptides in medium-sized neurons in the caudate putamen and with
      dynorphin in the paraventricular and supraoptic nuclei of the hypothalamus.
      Expression of RHS2 in the caudate putamen was increased by elimination of its
      nigrostriatal dopaminergic innervation.

PMID- 1348859
TI  - P-type voltage-dependent calcium channel mediates presynaptic calcium influx and
      transmitter release in mammalian synapses.
AB  - We have studied the effect of the purified toxin from the funnel-web spider venom
      (FTX) and its synthetic analog (sFTX) on transmitter release and presynaptic
      currents at the mouse neuromuscular junction. FTX specifically blocks the omega
      conotoxin- and dihydropyridine-insensitive P-type voltage-dependent Ca2+ channel
      (VDCC) in cerebellar Purkinje cells. Mammalian neuromuscular transmission, which
      is insensitive to N- or L-type Ca2+ channel blockers, was effectively abolished
      by FTX and sFTX. These substances blocked the muscle contraction and the
      neurotransmitter release evoked by nerve stimulation. Moreover, presynaptic Ca2+
      currents recorded extracellularly from the interior of the perineural sheaths of
      nerves innervating the mouse levator auris muscle were specifically blocked by
      both natural toxin and synthetic analogue. In a parallel set of experiments, K(+)
      induced Ca45 uptake by brain synaptosomes was also shown to be blocked or greatly
      diminished by FTX and sFTX. These results indicate that the predominant VDCC in
      the motor nerve terminals, and possibly in a significant percentage of brain
      synapses, is the P-type channel.

PMID- 1348860
TI  - Identification of a mammalian 10-kDa heat shock protein, a mitochondrial
      chaperonin 10 homologue essential for assisted folding of trimeric ornithine
      transcarbamoylase in vitro.
AB  - We have identified a 10-kDa stress-inducible mitochondrial protein. The protein
      is synthesized at elevated rates in cultured rat hepatoma cells challenged with
      heat shock or amino acid analogues and, therefore, designated heat shock protein
      10 (Hsp10). Hsp10 was purified to homogeneity from rat liver and found to exhibit
      a native molecular mass of 65 kDa, as opposed to a monomeric molecular mass of
      10,813.4 +/- 0.41 Da. The amino acid sequence of rat Hsp10 disclosed extensive
      sequence similarity with bacterial chaperonin (Cpn) 10. Rat Hsp10 and Escherichia
      coli Cpn60 were used to reconstitute functional trimeric rat ornithine
      transcarbamoylase from a chemically denatured state with high efficiency. This
      process depended completely upon rat Hsp10 and was abolished in the presence of a
      nonhydrolyzable ATP analogue. We conclude that Hsp10 is a eukaryotic Cpn10
      homologue and, therefore, together with Cpn60 essential for mitochondrial protein
      biogenesis. The Cpn-mediated protein-folding apparatus, thus, exhibits a high
      degree of conservation between prokaryotes and mitochondria of higher eukaryotes.

PMID- 1348864
TI  - Biology and pathology of the macrophage. Fifth Annual Conference of the Upper
      Rhine Universities on the Macrophage. Strasbourg, France, September 4-5, 1991.

PMID- 1348862
TI  - Genetic transfer of non-P-glycoprotein-mediated multidrug resistance (MDR) in
      somatic cell fusion: dissection of a compound MDR phenotype.
AB  - A non-P-glycoprotein-mediated mechanism of multidrug resistance (non-Pgp MDR) has
      been identified in doxorubicin-selected sublines of the human non-small cell lung
      carcinoma cell line SW-1573. These sublines are cross-resistant to daunorubicin,
      VP16-213, Vinca alkaloids, colchicine, gramicidin D, and 4'-(9
      acridinylamino)methanesulfon-m-anisidide (m-AMSA). They accumulate less drug than
      the parental cells and their resistance is not due to the MDR1-encoded P
      glycoprotein, as the resistant cell lines have lost the low amount of MDR1 mRNA
      detectable in parental cells. Here we show that the resistant cell lines also
      contain less topoisomerase II mRNA and enzyme activity than the parental cells.
      This might contribute to the resistance of these lines to drugs interacting with
      topoisomerase II, such as doxorubicin, daunorubicin, and VP16-213, but cannot
      account for the resistance to the other drugs. We have tested whether all
      properties of the non-Pgp MDR cell lines cosegregate in somatic cell fusions
      between lethally gamma-irradiated, resistant donor cells and drug-sensitive
      acceptor cells. Whereas a MDR phenotype with reduced drug accumulation and the
      loss of MDR1 P-glycoprotein mRNA were cotransferred to the acceptor cells, the
      decrease in topoisomerase II gene expression was not. We conclude that the MDR
      phenotype, the reduced drug accumulation, and the loss of MDR1 P-glycoprotein
      mRNA are genetically linked. They might be due to a single dominant mutation,
      which does not cause the alteration in topoisomerase II.

PMID- 1348861
TI  - mRNA coding for neurotransmitter receptors in a human astrocytoma.
AB  - Electrophysiological techniques and Xenopus oocytes were used to study the
      expression of neurotransmitter receptors encoded by mRNAs isolated from three
      human glioma cell lines. Oocytes injected with mRNAs from two glioblastoma cell
      lines did not show electrical responses to the various neurotransmitters tested.
      In contrast, oocytes injected with mRNA from an astrocytoma cell line (R-111)
      acquired acetylcholine and glutamate receptors as well as a small number of N
      methyl-D-aspartate (NMDA) receptors. Acetylcholine elicited oscillatory Cl-
      currents that were abolished by muscarinic antagonists. The muscarinic receptors
      are coupled to the inositol phosphate-Ca2+ receptor-channel coupling system.
      Glutamate and its analogs kainate, quisqualate, and alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionic acid induced smooth currents. The non-NMDA responses
      were potently blocked by 6,7-dinitroquinoxaline-2,3 dione. Our results show that
      human astrocytoma cells contain mRNAs coding for functional acetylcholine and
      glutamate receptors that have properties similar to those of neurons. In
      contrast, human glioblastoma cells lacked those mRNAs. These differences might be
      useful for the development of new diagnostic and therapeutic procedures.

PMID- 1348863
TI  - [Lymphocytic alveolitis in the early stages of HIV infection: correlation with
      biological and prognostic factors].
AB  - Broncho-alveolar lavage was performed to assess the degree of pulmonary
      lymphocytic alveolitis in 32 asymptomatic patients who were infected with the
      Human Immunodeficiency Virus (VIH). The patients were stages II and III of the
      CDC classification and the aim of the study was to determine the frequency,
      nature and prognostic role of the findings. 62.5% of the subjects (20/32)
      presented with a lymphocytic alveolitis which consisted predominantly of CD8
      lymphocyte (64.3 +/- 3.5%), in the absence of an opportunistic infection or
      broncho-pulmonary tumours. Two sub-populations of alveolar CD8 were shown at
      comparable levels, a) sub-population CD8+D44+ (22.1 +/- 5%), in whom we showed
      the possession of cytotoxic activity in particular specific for VIH; b) sub
      population CD8+CD57+ (19.6 +/- 3%) which we have shown to be capable in vitro of
      inhibiting the effector phase of cytotoxic activity of CD8+D44+ alveolar cells
      specific for VIH. In this group of 32 patients the occurrence of an alveolitis
      was not correlated with the usual prognostic factors of infection by VIH measured
      simultaneously with broncho-alveolar lavage (the level of CD4+ blood lymphocytes,
      and the beta 2-plasma microglobulins and the presence of p24 antigenaemia). In
      addition the level of CD4 lymphocytes supperior to 400/mm3 and of beta 2
      microglobulins less then 3 mg/l whether a lymphocytic alveolitis was there or not
      confirmed the relatively poorly developed state of the VIH infection in these
      asymptomatic patients. Also the occurrence of a lymphocytic alveolitis did not
      seem to be linked to progression of the disease in the group of patients
      studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348866
TI  - On the HIV nef gene product. 3rd forum in virology.

PMID- 1348865
TI  - HIV1 quantitation in infected patients: a comparison of cell viraemia, plasma
      viraemia and R-HEV.
AB  - Anti-HIV1 trials require sensitive, reproducible and reliable parameters which
      measure virus load and virus production. The aim of the present study of 14
      patients at different CDC stages was to compare results provided by three
      techniques which evaluate, respectively, cell-associated HIV1 infectivity (cell
      viraemia), plasma-associated HIV1 infectivity (plasma viraemia) and radiation
      resistant expression ex vivo (R-HEV). For each patient, TCD4 lymphocytes were
      numbered and an HIV1 antigenaemia determination was carried out. We found no
      correlation between cellular viraemia and R-HEV; on the contrary, data concerning
      plasma viraemia and R-HEV were significantly correlated. While cellular viraemia
      and R-HEV were not correlated with TCD4 levels, plasma viraemia exhibited a
      significant negative correlation with TCD4 counts. Despite theoretical and
      practical differences, plasma viraemia and R-HEV may measure events in the viral
      replication cycle which bear a close resemblance; however, as designed, R-HEV
      seems to be far less discriminative than plasma viraemia.

PMID- 1348867
TI  - [A case of congenital long QT syndrome associated with T wave alternans].
AB  - A case was presented in which a rare T wave alternans occurred in association
      with congenital long QT syndrome. A 71-year-old woman, who had experienced
      several syncopal attacks per year for the previous forty years, was admitted for
      further evaluation of the syncope. She had a family history of sudden death
      (sister) and QT prolongation (son). Electrocardiogram showed a corrected QT
      interval of 0.68 seconds. Treadmill exercise-tolerance test revealed both T wave
      alternans immediately after exercise and torsades de pointes 150 seconds after
      exercise. The syncope was induced by the mental excitation. A prolonged corrected
      QT interval reduced from 0.70 seconds to 0.58 seconds by the correction of her
      serum potassium and magnesium. The effect of propranolol, verapamil, phenytoin or
      mexiletine on T wave alternans and ventricular arrhythmia was evaluated by the
      treadmill exercise-tolerance test. The treatment with propranolol was most
      effective.

PMID- 1348868
TI  - [New virological data: replication and persistence of the human immunodeficiency
      virus].
AB  - Human immunodeficiency virus behaves in vitro as an acutely replicating,
      cytopathic retrovirus. However, HIV infection in vivo is persistent and slowly
      progressive. Many virological properties of HIV could be involved in establishing
      the persistence of infection: the complex regulation of HIV replication,
      particularly of HIV gene expression; the requirement of cell activation for
      several steps of HIV replication; the role of HIV accessory genes; the great
      genetic variability of HIVs, allowing their adaptation to host responses in vivo.

PMID- 1348869
TI  - [Asthma therapy: are bronchodilators obsolete?].
AB  - Short acting beta 2-agonists, such as salbutamol, fenoterol and terbutaline, are
      the most potent bronchodilating agents in the treatment of acute asthmatic
      attacks. In chronic asthma, however, they must be viewed as purely symptomatic
      treatment compared to antiinflammatory agents (inhaled corticosteroids,
      cromoglycate and nedocromil sodium), prophylactic agents which can also decrease
      airway hyperresponsiveness and thereby stabilize the disease. Modern asthma
      treatment are based on the present understanding of asthma pathophysiology and
      take into account the new therapeutic options with high dose inhaled steroids and
      long acting beta 2-agonists. Patients with only occasional asthma symptoms should
      receive inhaled short acting beta 2-agonists as needed. These agents continue to
      be central to the treatment of any asthmatic attack. If asthma symptoms occur
      more than 4-6 times a week a regular inhalative antiinflammatory regimen should
      be initiated (e.g. inhalative corticosteroids b.i.d.). In cases with frequent
      symptoms or persisting airway obstruction, regularly administered inhalative
      bronchodilators (beta 2-agonists, possibly long acting) should be added to high
      dose inhaled steroids. Treatment of severe acute asthma should always include
      systemic glucocorticosteroids (e.g. prednisone 30-60 mg/day). Special emphasis
      should be placed on self-management plans, encouraging patients to monitor and
      treat their disease themselves in close cooperation with the physician.

PMID- 1348870
TI  - Balancing selection at allozyme loci in oysters: implications from nuclear RFLPs.
AB  - Population genetic analyses that depend on the assumption of neutrality for
      allozyme markers are used widely. Restriction fragment length polymorphisms in
      nuclear DNA of the American oyster evidence a pronounced population subdivision
      concordant with mitochondrial DNA. This finding contrasts with a geographic
      uniformity in allozyme frequencies previously thought to reflect high gene flow
      mediated by the pelagic gametes and larvae. The discordance likely is due to
      selection on protein electrophoretic characters that balances allozyme
      frequencies in the face of severe constraints to gene flow. These results raise a
      cautionary note for studies that rely on assumptions of neutrality for allozyme
      markers.

PMID- 1348871
TI  - Competition for overlapping sites in the regulatory region of the Drosophila gene
      Kruppel.
AB  - A 730-base pair element regulates expression of the Drosophila gap gene Kruppel
      (Kr) in response to the fly anterior morphogen bicoid (bcd). Two hormone receptor
      like proteins, encoded by the genes knirps (kni) and tailless (tll), bind
      specifically to the element. In vitro, kni protein competes with the homeodomain
      containing bcd protein in binding to a 16-base pair target sequence. In vivo
      experiments suggest that both kni and tll act as competitive repressors of bcd
      mediated activation of Kr. These results suggest a mechanism by which
      developmental genes can be regulated in response to an activating morphogen
      gradient antagonized by repressors.

PMID- 1348872
TI  - Use of a dihydrogen osmium complex as a versatile 1H NMR recognition probe.
AB  - A new recognition probe for biomolecules, [en2Os(eta 2-H2)]2+ (1; en,
      ethylenediamine), is reported. In aqueous solution, 1 binds readily to a variety
      of biomolecules, including nucleotides, RNA, amino acids, peptides, and
      phospholipids. In each case, binding leads to a characteristic proton nuclear
      magnetic resonance (1H NMR) for the dihydrogen that appears in a spectral window
      in the range delta = 0 to -20 parts per million, and as well to characteristic
      values of the coupling JHD and of the relaxation time T1. Small structural
      differences in molecules such as DGMP (2'-deoxyguanosine 5'-monophosphate) and
      IMP (inosine 5'-monophosphate) or Asp and Glu can readily be distinguished, such
      as when 1 binds to the N-7 position of the nucleobase of DGMP or IMP and when 1
      binds to the carboxylate of Asp or Glu. Upon one-electron oxidation of the metal
      center, diamagnetic 1 is converted to a paramagnetic probe.

PMID- 1348873
TI  - Functional complementation of yeast ste6 by a mammalian multidrug resistance mdr
      gene.
AB  - Multidrug resistance in mammalian tumor cells is associated with the
      overexpression of mdr genes encoding P-glycoproteins, which function as drug
      efflux pumps. A yeast homolog of mdr, STE6, mediates export of a-factor mating
      peptide. Yeast MATa cells carrying a ste6 deletion produce no extracellular a
      factor and therefore are defective in mating. Expression of a complementary DNA
      for the mouse mdr3 gene in a yeast ste6 deletion strain restored ability to
      export a-factor and to mate. A mutation (a serine to phenylalanine substitution
      at amino acid 939) known to affect the activity of the mdr3 gene product
      abolished its ability to complement the yeast ste6 deletion. Thus, functions of P
      glycoproteins in normal mammalian cells may include the transmembrane export of
      endogenous peptides.

PMID- 1348874
TI  - Chemists vie to make a better taxol.

PMID- 1348875
TI  - [Malaria in childhood: its prevention and treatment].

PMID- 1348876
TI  - Magnetic resonance imaging of tendon and ligament abnormalities: Part II. Pelvis
      and lower extremities.
AB  - Magnetic resonance imaging (MRI) has provided an ideal means, unmatched by other
      preexisting modalities, of examining musculoskeletal abnormalities, particularly
      those involving tendons and ligaments in the lower extremities. Lack of motion
      artifact, convenience of application of surface coil, and absence of overlying
      structures have made the lower extremities ideally suited to MRI. In addition,
      the abundance of adjacent adipose tissue provides a superb contrast background.
      Although evaluation of trauma remains the most common reason for MRI examination,
      many other conditions may also affect tendons and ligaments. As in other soft
      tissue, chondral, and osteochondral lesions, MRI provides exquisite details of
      abnormalities in these structures. Part II of this review systematically reviews
      the abnormalities of tendons and ligaments in the pelvis and lower extremities.

PMID- 1348878
TI  - Laparoscopy for the non-palpable testis--look before you cut!
AB  - Before definitive surgery laparoscopies were performed to define the position of
      24 non-palpable testes in 21 patients. The anatomical site of the testes was
      confirmed by surgery in all cases. Laparoscopy is helpful in planning the
      definitive procedure in these cases.

PMID- 1348877
TI  - Dissection of the uncinate process during pancreatoduodenectomy.
AB  - An alternative approach to the dissection of the uncinate process during
      pancreatoduodenectomy is described. This involves mobilisation of the midgut
      superiorly and bringing the uncinate process into an antero-inferior position
      within the operative field. Access to, and visualisation of, the posterior aspect
      of the superior mesenteric vessels is considerably improved. This approach may
      avoid many of the potential problems associated with freeing of the uncinate
      process during pancreatic resection.

PMID- 1348879
TI  - Ecstasy--a dangerous drug.

PMID- 1348880
TI  - The influence of antihypertensive agents on circadian rhythms of blood pressure
      and heart rate in patients with essential hypertension.
AB  - The effects of once-daily administration of calcium (Ca) channel blockers, beta
      blockers and and angiotensin-converting enzyme (ACE) inhibitors on circadian
      rhythms of blood pressure (BP) and heart rate (HR) were studied using the cosinor
      method. Sixty-two recruited patients with essential hypertension (WHO stage I or
      II) were divided into three groups based on the class of administered drugs. In
      the Ca channel blocker group (n = 37, age 54 +/- 9.0 years), 18 patients were
      given YM 730 at a mean dose of 11 +/- 4.0 mg/day (mean +/- S.D.), 8 were given
      nitrendipine (11 +/- 6.7 mg/day), and 11 were given nisoldipine (8 +/- 6.4
      mg/day). In the beta-blocker group (n = 15, age 42 +/- 13.5 years), 13 patients
      were given atenolol (44 +/- 11.0 mg/day), 1 was given nadolol (30 mg/day), and 1
      was given sustained-release propranolol (60 mg/day). In the ACE inhibitor group
      (n = 10, age 56 +/- 8.7 years), 7 patients were given enalapril (6 +/- 2.8
      mg/day), and 3 were given lisinopril (20 mg/day). Ambulatory BP monitoring (ABPM)
      was performed before and during treatment. Mean arterial pressure (MAP) and HR
      were monitored under ambulatory conditions every five minutes for 24 hr with a
      finger volume oscillometric device. In all three groups, the mesor of MAP
      decreased significantly, while the amplitude and acrophase did not change during
      treatment. beta-Blockers reduced the amplitude as well as the mesor of HR. Ca
      channel blockers increased the amplitude of HR without influencing the mesor. ACE
      inhibitors had no effect on the circadian rhythm parameters of HR. These results
      suggest that Ca channel blockers, beta-blockers and ACE inhibitors lowered BP
      throughout the day without changing the circadian BP rhythm. However, the three
      drug classes may have different influences on the autonomic nervous system that
      regulates circadian cardiac rhythm.

PMID- 1348881
TI  - Exogenous Thy-1.1 expression as a marker for thymocyte maturation in transgenic
      mice.
AB  - We established a line of transgenic mice carrying the exogenous mouse Thy-1.1
      gene (8.2 Kb Eco RI genomic DNA fragment). In these mice, Thy-1.1 was expressed
      on thymocytes but not on peripheral T cells, presumably due to the lack of cis
      acting element(s) on the microinjected genomic DNA. Even in the thymus, however,
      while most of the CD3/TCR- thymocytes were positive for the transgenic Thy-1.1
      gene expression, the CD4+ or CD8+ single positive (SP) thymocytes were composed
      of two groups, one Thy-1.1+ and one Thy-1.1-, suggesting that the former belongs
      to cells at premature stages of terminal T cell differentiation. There was no
      difference in the amount of CD3/TCR complexes expressed on two such SP thymocyte
      subsets. In the double negative (DN) thymocytes, all the CD3/TCR+ cells were Thy
      1.1-. These results suggest that the maturational process of CD3+ DN thymocytes
      differs from that of SP thymocytes. The unique distribution of Thy-1.1+
      population among CD3+ thymocytes suggests that the transgenic Thy-1.1 gene
      expression can serve as a useful marker to examine terminal maturation processes
      of CD3+ thymocytes.

PMID- 1348882
TI  - Ejection of malaria sporozoites by feeding mosquitoes.

PMID- 1348883
TI  - Monoclonal antibodies against human T cell adhesion molecules--modulation of
      immune function in nonhuman primates.
AB  - The cytotoxic T cell is thought to be a primary effector of allograft rejection.
      In vitro studies have demonstrated that the interaction between cytotoxic T cells
      and target cells involves cell surface adhesion molecules that result in
      conjugate formation, with subsequent antigen recognition, T cell activation, and
      target cell lysis. Experiments have also demonstrated the ability of monoclonal
      antibodies with specificity for two human T cell adhesion molecules, lymphocyte
      function associated (LFA) antigen-1 (LFA-1, CD11a, alpha-chain/CD18, beta-chain)
      and LFA-2 (CD2), to inhibit conjugate formation in vitro. Studies in a nonhuman
      primate model were undertaken to determine whether the in vivo administration of
      monoclonal antibodies with specificity for the alpha chain of LFA-1 (CD11a) or
      with specificity for CD2 could modulate in vivo T cell function. Cynomolgus
      monkeys (Macaca fascicularis) received 10 daily intravenous infusions of either
      anti-CD11a, anti-CD2 or both anti-CD11a and anti-CD2 monoclonal antibodies.
      Antibody administration was well tolerated and resulted in high levels of
      circulating murine monoclonal antibody in the peripheral circulation. Nearly all
      the animals generated antimurine antibodies that were specific for both idiotypic
      and nonidiotypic determinants of the infused mouse protein. Circulating
      lymphocytes and T cells were not depleted by treatment with anti-CD11a or anti
      CD2 mAbs; in fact, treatment with the combination of anti-CD11a plus anti-CD2 or
      anti-CD11a alone led to increased numbers of circulating lymphocytes and T cells.
      Modulation of the LFA-1 molecule on circulating T cells occurred as a result of
      treatment with anti-CD11a (or the combination of anti-CD11a plus anti-CD2),
      whereas treatment with anti-CD2 (or anti-CD11a plus anti-CD2) did not result in
      modulation of the CD2 antigen despite detectable levels of circulating anti-CD2
      mAb. In vivo T cell function was assessed by placement of skin allografts. As
      compared with treatment with saline or a control mAb, allograft survival was
      significantly prolonged in animals treated with anti-CD11a or combination
      treatment but not in animals receiving anti-CD2 alone. We conclude that the in
      vivo administration of anti-LFA-1 mAb may be useful for the blockade of effector
      T cell activity during allograft rejection, that saturation of antigen and
      antigen modulation may be important for efficacy of such antibody effects in
      vivo, and that monoclonal antibodies with specificity for functionally important
      T cell surface molecules may alter T cell function in vivo without lymphocyte
      depletion.

PMID- 1348885
TI  - Proceedings of the First International Congress on Xenotransplantation.
      Minneapolis, Minnesota, August 25-28, 1991.

PMID- 1348884
TI  - Stimulation of CD4+ T lymphocytes by allogeneic MHC peptides presented on
      autologous antigen-presenting cells. Evidence of the indirect pathway of
      allorecognition in some strain combinations.
AB  - A preliminary analysis of the alloantibody response to free, unconjugated class I
      and class II MHC peptides in several rat and mouse strains was performed, to
      screen for an effective interaction between the allogeneic MHC peptides and
      recipient MHC molecules. The PVG rat strain was noted to produce very strong, MHC
      restricted, primary and secondary responses to a synthetic peptide derived from
      the alpha helical region of the alpha 2 domain of an RT1.C/E class I MHC molecule
      of the DA strain. In vitro proliferation studies demonstrated that CD4+ but not
      CD8+ T cells of the PVG strain responded in a recipient APC-dependent manner to
      the peptide, whereas the BN strain (which showed no antibody response to this
      peptide) gave no T cell proliferation. Immunization of PVG rats with the peptide
      did not influence the rejection of DA skin allografts. The relevance of these
      studies to the possible mechanisms of allograft rejection by an indirect pathway
      are discussed.

PMID- 1348886
TI  - Evidence for thymic maturation of both rat and mouse T cells in mixed xenogeneic
      chimeras (B10 mouse+F344 rat----B10 mouse).

PMID- 1348887
TI  - Hemopoietic chimerism in rodents transplanted in utero with fetal human
      hemopoietic cells.

PMID- 1348888
TI  - What's in a homeobox. The development of pattern during embryonic growth.

PMID- 1348889
TI  - Cell kinetic analyses and expression of carcinoembryonic antigen, carbohydrate
      antigen 19-9 and DU-PAN-2 in hyperplastic, pre-neoplastic and neoplastic lesions
      of intrahepatic bile ducts in livers with hepatoliths.
AB  - We evaluated cell proliferative activity and expression of carcinoembryonic
      antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and DU-PAN-2 in various bile
      duct lesions in livers with hepatoliths, using histochemical and
      immunohistochemical methods. Histologically, the bile duct lesions were divisible
      into hyperplasia, dysplasia, adenocarcinoma in situ and invasive adenocarcinoma.
      All cases showed mucosal hyperplasia in stone-bearing bile ducts. Livers with
      invasive adenocarcinoma frequently contained adenocarcinoma in situ and
      dysplasia, and livers with adenocarcinoma in situ occasionally harboured
      dysplasia. Proliferating cell nuclear antigen (PCNA) labelling index was low in
      hyperplasia (mean +/- SD = 20.5 +/- 8.7%), intermediate in dysplasia (35.4 +/-
      15.9%), and high in adenocarcinoma in situ (46.4 +/- 9.3%). The mean number of
      argyrophilic nucleolar organizer regions (AgNORs) was low in hyperplasia (1.52),
      intermediate in dysplasia (2.26) and high in adenocarcinoma in situ (2.69). There
      was a significant positive correlation between PCNA labelling index and AgNORs
      count. CEA was expressed on invasive adenocarcinoma cells and adenocarcinoma in
      situ cells in most cases and on dysplastic cells in about a half, while CEA was
      never present in hyperplastic epithelia. Expression of CA 19-9 was low in
      adenocarcinoma, intermediate in dysplasia and rather high in hyperplasia. There
      was no significant difference in DU-PAN-2 expression among these bile duct
      lesions. These data suggest that cell replicative activity is low in hyperplasia,
      intermediate in dysplasia and high in adenocarcinoma in situ, and that CEA
      appears in the following order: dysplasia, adenocarcinoma in situ, invasive
      adenocarcinoma. We suggest that carcinogenesis in biliary epithelial in livers
      with stones is a multi-step process through hyperplasia, dysplasia and
      adenocarcinoma in situ to invasive adenocarcinoma.

PMID- 1348891
TI  - Establishment and characterisation of two cell lines with different grade of
      differentiation derived from one primary human pancreatic adenocarcinoma.
AB  - From a liver metastasis of a human pancreatic adenocarcinoma, we have established
      cell lines for studying the cell biology of this tumor. We obtained two cell
      lines with different morphological, chromosomal and functional properties. One of
      them, named PaTu 8988s, revealed a solid growth in nude mouse xenografts with
      cells exhibiting only occasional polar organisation of the cytoplasm. In general,
      no apical or basolateral plasma membrane domains could be distinguished and the
      sparse organelles were randomly distributed throughout the cytoplasm. Secretory
      products, such as mucin, were weakly stained histochemically or were completely
      absent. Transglutaminase (TGase) activity used as a marker for cellular
      differentiation was low in these cells. The other cell line, named PaTu 8988t,
      grew tumors composed of tubular structures when injected subcutaneously into nude
      mice. Cells were polarized with distinct apical and basolateral plasma membranes
      and the cytoplasmatic organelles were arranged with the nucleus in the lower part
      of the cell, while the apical cytoplasm contained the Golgi complex and numerous
      secretion granules. A high content of mucin was stained histochemically and
      transglutaminase activity was ten times higher than in PaTu 8988s. Comparing the
      chromosome number per metaphase plate, both cell lines showed a major peak, with
      45-55 chromosomes per metaphase plate in PaTu 8988s and about 110-120 chromosomes
      per metaphase plate in PaTu 8988t. When the two cell lines were injected
      intravenously into the tail vein of nude mice, only PaTu 8988s developed
      metastases localized exclusively in the lung, whereas PaTu 8988t produced no
      metastases in any organ. We conclude, that two cell lines exhibiting different
      grades of differentiation as well as a different potency to metastasize can be
      established from the same primary tumor, and that these cell lines represent a
      suitable model for further study of the cell biology of human pancreatic
      adenocarcinoma.

PMID- 1348890
TI  - Immunohistochemical studies on oncogene products (EGF-R, c-erbB-2) and growth
      factors (EGF, TGF-alpha) in human breast cancer: their relationship to oestrogen
      receptor status, histological grade, mitotic index and nodal status.
AB  - In this investigation, 83 human mammary carcinomas were examined for the
      expression of oestrogen receptor (ER), epidermal growth factor receptor (EGF-R),
      epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), c
      erbB-2, histological grade, mitotic index and nodal status, all of which are
      reportedly prognostically significant factors (Bloom and Richardson 1957; Baak et
      al. 1985; Wright et al. 1989). ER expression was biochemically recognized in
      43.4% of mammary carcinomas, and EGF-R, EGF, TGF-alpha and c-erbB-2 were
      histochemically recognized in 25.3, 14.5, 27.7 and 18.0% of mammary carcinomas
      examined respectively, using conventional sections of buffered formalin-fixed,
      paraffin-embedded tissue and monoclonal or polyclonal antibodies. There were
      significant relationships between negative ER and positive EGF-R or TGF-alpha;
      positive EGF-R and TGF-alpha; positive EGF-R and c-erbB-2; and positive c-erbB-2
      and TGF-alpha. The single changes which were the negative ER and the positive c
      erbB-2 correlated with histological grade and mitotic index. Co-expression of EGF
      R and TGF-alpha correlated with positive nodal status. Therefore, the present
      investigation indicates that the negative ER, single expression of c-erbB-2 and
      co-expression of EGF-R and TGF-alpha are important markers which contribute
      indirectly to prognosis, which reconfirms previous findings on the former two
      while adding the new finding that immunohistochemical demonstration of expression
      of EGF-R and TGF-alpha may provide useful information for selecting the
      appropriate treatment.

PMID- 1348892
TI  - Autometallographic detection of mercury in rat spinal cord after treatment with
      organic mercury.
AB  - Autometallography was used to localize mercury in rat spinal cord after
      intraperitoneal administration of methylmercuric chloride (200 micrograms CH3HgCl
      daily). The technique permits small amounts of mercury sulfides and mercury
      selenides to be visualized by silver-enhancement. Mercury deposits were observed
      by light microscopy only in neurons. In all of the spinal cord segments selected
      (first cervical segment, C1; fifth cervical segment, C5; sixth thoracic segment,
      T6; and first lumbar segment, L1) the mercury was observed with cumulative
      dosages of 6000 micrograms CH3HgCl and greater. Laminae VII, VIII, and IX
      contained the majority of stained neurons, whereas laminae IV, V, VI, and X had a
      relatively lower density of mercury-containing neurons. Stained neurons were
      confined to specific cell groups, such as Clarke's column, nucleus intermedio
      lateralis, nucleus cervicalis centralis, and nucleus dorsomedialis. At the
      ultrastructural level, mercury deposits were restricted to lysosomes of neurons
      and occasional accumulations in the lysosomes of ependymal cells.

PMID- 1348893
TI  - Distribution of retinol-binding protein in the human digestive tract.
AB  - By employing polyclonal antibodies for retinol-binding protein (RBP), its
      distribution in the human pancreas and digestive tract mucosa was compared with
      those of transthyretin (TTR) and various peptide hormones. The materials used
      included surgically removed pancreas, esophagus, stomach, small and large
      intestines. Paraffin sections were stained by the indirect immunoenzyme method.
      The results indicate that RBP-containing cells are found in the pancreas and the
      gastrointestinal mucosa, but most frequently in the gastric antrum and duodenum.
      In the pancreas, RBP-containing cells are found in the islets and among acinar
      and ductal epithelial cells, and consistently stain for chromogranin A. RBP
      containing cells in the gastrointestinal mucosa showed typical features of
      endocrine cells and also stained for chromogranin A. The distribution of TTR in
      these tissue sites resembled that of RBP, but the immunoreactive intensities of
      both peptides altered independently. Comparison of the distribution of RBP, TTR,
      and various gastrointestinal peptide hormones revealed that the distribution of
      RBP coincided with none of the other peptides, although some of the RBP
      containing cells stained for most of the peptides examined and vice versa. These
      results suggest that RBP may be a consistent component of gastrointestinal
      endocrine cells.

PMID- 1348894
TI  - Effects of X-irradiation and adriamycin on quiescent and proliferating cells of
      the seminal vesicle in the castrated mouse.
AB  - The sensitivity of resting and proliferating cells of the seminal vesicle to X
      irradiation and adriamycin has been investigated. Stimulation with testosterone
      propionate (250 micrograms/day) was started 11 days after castration in BALB/c
      mice. X-rays (2.5-7.5 Gy total body irradiation) and intraperitoneal injections
      of adriamycin (4-16 mg/kg body weight) were administered at various times before
      or after induction of proliferation by testosterone injection. The DNA contents
      and the weights of the seminal vesicles were determined at 4 days after the start
      of stimulation. A Do for X-rays of about 10 Gy was found for the seminal vesicle
      epithelium. For both X-irradiation and adriamycin no significant differences in
      sensitivity were observed between quiescent (Go) and proliferating (G1; S)
      seminal vesicle cells.

PMID- 1348895
TI  - The distribution of alpha 1-antichymotrypsin and amyloid production in the brain
      in Alzheimer's disease.
AB  - In this immunohistopathological study alpha 1-antichymotrypsin, which is barely
      demonstrable in the normal brain, was found in amyloid fibrils, endothelial cells
      and the cytoplasm of astroglial cells in brains from patients with Alzheimer's
      disease. Amyloid precursors stained with methenamine silver were arrayed mainly
      along the membranes, and amyloid fibrils, which stained densely with anti-alpha 1
      antichymotrypsin, were in direct contact with the fibrous structures connecting
      with the membranes of vascular feet or astrocytic processes. From the above
      findings, alpha 1-antichymotrypsin seems to play a role in the production of
      amyloid fibrils in Alzheimer's disease.

PMID- 1348896
TI  - The role of macrophages in the uptake of endotoxin by the mouse liver.
AB  - The purpose of this investigation was to analyse the macrophage subpopulations
      involved in the uptake of endotoxin in the liver. The results show that in normal
      B10.D2 mice the liver macrophages constitute a heterogeneous population of cells
      which, depending on their state of differentiation, are distinguished by their
      differential distribution in the liver acinus and by their ability to phagocytose
      latex. Following the intravenous administration of endotoxin (lipopolysaccharide
      = LPS) from Salmonella abortus equi, endotoxin-carrying non-parenchymal cells of
      the liver (NPLC) were investigated immunohistochemically (in situ) and
      immunocytochemically (after isolation) between 1 h and 14 days after the
      injection. The endotoxin content of the blood and of isolated NPLC was also
      determined, using radioactivity labeled LPS. Following LPS injection, the total
      number of macrophages in the liver increased, reaching a maximum after 3 days.
      There was a striking increase in the ratio of mature to immature macrophages.
      After day 3, the number of macrophages decreased again, returning to the pre
      injection values by day 14. 1 h after the administration of LPS, 41% of the
      isolated NPLC were already endotoxin-positive, a percentage which remained
      constant until the 3rd day. Thereafter, the number of LPS-bearing cells increased
      to a maximum of about 52% on the 5th day. This increase mostly involved
      macrophages which had taken up endotoxin. Concurrent with these changes there was
      a threefold increase in radioactivity-labeled LPS from the 7th h to the 5th day
      after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348897
TI  - Ultrastructural study of the glomerular slit diaphragm in fresh unfixed kidneys
      by a quick-freezing method.
AB  - In normal kidneys fixed by perfusion with tannic acid and glutaraldehyde,
      glomerular slit diaphragms have been reported to consist of highly ordered and
      isoporous substructures with a zipper-like configuration. We have re-evaluated
      the ultrastructure of fixed or unfixed glomeruli using quick-freezing and deep
      etching (QF-DE) and freeze-substitution (QF-FS) methods. In the fixed slit
      diaphragms, zipper-like substructures were often observed by the QF-DE method. In
      contrast, in fresh unfixed glomeruli the slit diaphragms mainly consisted of non
      porous substructures. The slit diaphragms were more widely opened in the fixed
      glomeruli, as examined by the QF-FS method. These results suggest that the foot
      processes shrink during tissue preparation by conventional methods with chemical
      fixatives, and that the broadening of slit diaphragms and zipper-like
      substructures are formed by the pulling apart of adjacent foot processes due to
      shrinkage.

PMID- 1348898
TI  - IVth Belgian Week of Gastroenterology. February 27-29, 1992. Abstracts.

PMID- 1348900
TI  - The constant region genes of the immunoglobulin heavy chains.

PMID- 1348901
TI  - Treatment of bile duct stones by laser lithotripsy: results in 12 patients.
AB  - We used a pulsed tunable dye laser (operating at 60 mJ per pulse, 504-nm
      wavelength) to fragment large (0.8-4.5 cm) stones retained in the hepatic ducts
      or common bile duct in 12 patients after cholecystectomy. Attempts to extract
      stones via a T-tube or endoscope had been unsuccessful in all patients. In nine
      of 12 patients, all stone fragments were successfully eliminated during the
      initial treatment. In one patient, fragmentation occurred but debris remained,
      requiring endoscopic stenting. Pseudomonas sepsis developed in this patient 30
      days after the procedure and was treated by extraction of the stone fragments.
      Fragments remaining after lithotripsy were cleared at the same sitting by using
      saline flushing or endoscopic or percutaneous basket extraction. In two of 12
      patients, the treatment was unsuccessful because of laser malfunction. The
      treatment was performed without complications, except for clinically
      insignificant hyperamylasemia, which occurred in two patients. Our experience
      suggests that laser lithotripsy offers a safe alternative for nonsurgical
      treatment of large retained biliary stones for patients in whom traditional
      treatments have failed.

PMID- 1348899
TI  - Influence of Parkinson's disease on oral health.
AB  - Thirty patients with Parkinson's disease were investigated with regard to their
      oral health. They had significantly more teeth and less caries than a control
      group of corresponding age. However, the salivary secretion rate was
      significantly lower with advancing parkinsonian symptoms. It is concluded that
      not only motor impairment but also autonomic dysfunction, as an expression of a
      more advanced neuron degeneration, could be of importance when the possibility of
      maintaining a good oral health in parkinsonian patients is considered.

PMID- 1348902
TI  - Toxic encephalopathy.

PMID- 1348904
TI  - Hormones increase oxygen uptake in periportal and pericentral regions of the
      liver lobule.
AB  - The effect of several hormones known to alter intracellular free Ca2+ on rates of
      O2 uptake in periportal and pericentral regions of the liver lobule was studied
      in the perfused liver. Regional O2 uptake was measured by stopping the flow and
      monitoring the decrease in O2 concentration. When perfusion was in the
      anterograde direction, basal rates of O2 uptake were two to three times higher in
      periportal than in pericentral regions, and phosphorylase alpha activity, which
      increases as a function of intracellular free Ca2+ levels, was higher in
      periportal regions. In contrast, when perfusion was in the retrograde direction,
      rates of O2 uptake were two to three times greater in pericentral regions.
      Infusion of epinephrine (0.1 microM) or angiotensin II (5 nM) increased the rate
      of O2 uptake nearly exclusively in downstream areas of the lobule where O2
      tension was low. When perfusions were in the anterograde direction, epinephrine
      increased phosphorylase alpha activity significantly only in pericentral regions.
      Stimulation of O2 uptake by epinephrine was blocked by the alpha-adrenergic
      receptor blocker phentolamine (1 microM) but not by the beta-receptor blocker
      propranolol. Thus hormones that increase intracellular calcium stimulate O2
      uptake predominantly in regions of the liver lobule where O2 tension is lowest,
      supporting the hypothesis that oxygen tension regulates O2 uptake in the liver
      via mechanisms involving intracellular free Ca2+.

PMID- 1348903
TI  - Restoration of stable metabolic conditions during islet suppression in dogs.
AB  - These studies were undertaken to examine the stability of metabolic conditions
      during islet suppression with fixed-rate insulin and glucagon replacement.
      Somatostatin was infused peripherally at 0.8 microgram.min-1.kg-1, insulin was
      infused intraportally at 200 microU.min-1.kg-1, and glucagon was infused
      intraportally at 0, 0.6, 1, 2, 5, or 20 ng.min-1.kg-1 in conscious overnight
      fasted dogs. [3-3H]glucose was infused for measurement of glucose kinetics.
      During infusion, plasma insulin was 7.2 +/- 0.4 microU/ml. Plasma glucagon rose
      linearly with glucagon dose, achieving basal levels at 2 ng.min-1.kg-1 infusion
      (164 +/- 18 vs. basal = 182 +/- 57 pg/ml). Plasma glucose and hepatic glucose
      output (HGO) decreased from basal at doses 0, 0.6, and 1 ng.min-1.kg-1, increased
      from basal at doses 5 and 20 ng.min-1.kg-1, and remained close to basal at dose 2
      ng.min-1.kg-1 (92 +/- 20 vs. basal = 99 +/- 3 mg/dl and 2.4 +/- 0.2 vs. basal =
      2.7 +/- 0.2 mg.min-1.kg-1 for glucose and HGO, respectively; P greater than
      0.47). Glucose clearance and blood lactate were also closely matched to basal at
      dose 2 ng.min-1.kg-1. Coefficients of variation during 2 ng.min-1.kg-1 glucagon
      infusion (last hour) were 3.4, 4.6, 4.9, and 4.7% for glucose, HGO, clearance,
      and lactate, respectively. These findings indicate that fasting metabolic
      conditions, as inferred from blood glucose, lactate, insulin, and glucagon
      levels, and the rates of glucose production and uptake can be recreated in toto
      during fixed-rate islet hormone replacement.

PMID- 1348905
TI  - Pertussis toxin-sensitive and pertussis toxin-insensitive inhibition of parietal
      cell response to GLP-1 and histamine.
AB  - We have recently shown that in rat parietal cells the glucagon-like peptide 1
      (GLP-1) variants 7-36 amide, 1-37, and 1-36 amide stimulate H+ production as
      indirectly measured by [14C]aminopyrine (AP) accumulation. This response to the
      GLP-1 peptides was intracellularly mediated by activation of adenylate cyclase
      and by adenosine 3',5'-cyclic monophosphate (cAMP) as second messenger. In the
      present study, we compared prostaglandin (PG)E2, somatostatin, and the protein
      kinase A antagonist Rp-adenosine-3',5'-monophosphorothioate (Rp-cAMPS) with
      respect to their inhibitory effects on parietal cell function induced by GLP-1 or
      histamine. PGE2 and somatostatin noncompetitively inhibited AP accumulation and
      cAMP production in response to the GLP-1 variants and histamine (IC50): [mean
      inhibitory concn 5 x 10(-9) M PGE2; 3 x 10(-7) somatostatin]; at their maximal
      concentrations PGE2 (10(-7) M) and somatostatin (10(-6) M) caused 85 and 65%
      inhibition, respectively. Treatment with pertussis toxin (PT; 250 ng/ml; 4 h)
      reversed the inhibitory effect of PGE2 and somatostatin on AP accumulation and
      cAMP production. At 2 x 10(-3) M (IC50: 3 x 10(-4) M) Rp-cAMPS completely
      inhibited AP accumulation induced by the GLP-1 variants or histamine; this effect
      was insensitive to PT. Specificity of Rp-cAMPs as protein kinase A inhibitor is
      suggested by inhibition of AP accumulation in response to Sp-cAMPS and N6,O2
      dibutyryl adenosine 3',5'-cyclic phosphate sodium, and forskolin, activators of
      protein kinase A and adenylate cyclase, respectively. We conclude that the
      parietal cell responses to GLP-1 and histamine are inhibited by identical
      mechanisms. Effects of PGE2 and somatostatin are mediated by the PT-sensitive
      subunit of adenylate cyclase Gi, whereas Rp-cAMPS interferes with cAMP-dependent
      mechanisms that are insensitive to PT.

PMID- 1348906
TI  - Peptone stimulates gastrin secretion from the stomach by activating bombesin/GRP
      and cholinergic neurons.
AB  - The mechanism by which partly digested protein (peptone) stimulates gastrin
      secretion was examined in isolated antral tissues with intact intramural
      innervation. In the isolated vascularly perfused rat stomach, luminal perfusion
      with 0.5% peptone increased gastrin (62 +/- 14 pg/min; P less than 0.01) and
      decreased somatostatin (74 +/- 19; P less than 0.01) secretion. The axonal
      blocker tetrodotoxin (TTX) abolished the gastrin and somatostatin responses
      indicating that the responses were neurally mediated. Atropine partly inhibited
      the gastrin response (50%) and converted the somatostatin response to an increase
      above basal level. The selective bombesin/gastrin-releasing peptide (GRP)
      antagonist [Leu13-psi(CH2NH)-Leu14]-bombesin partly inhibited the gastrin
      response (65%) and caused a further decrease in somatostatin secretion. A
      combination of atropine and the bombesin/GRP antagonist, like TTX, abolished the
      gastrin and somatostatin responses. The pattern of response to peptone in
      superfused antral segments was identical to that in the vascularly perfused
      stomach. In fundic segments that do not secrete gastrin, the somatostatin
      response to peptone alone and with various antagonists was identical to that in
      antral segments. The results indicate that peptone stimulates gastrin secretion
      by activating stimulatory cholinergic and bombesin/GRP neurons. Cholinergic
      neurons stimulate gastrin directly as well as indirectly by eliminating the
      inhibitory paracrine influence of somatostatin.

PMID- 1348907
TI  - Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in
      the canine pylorus in vivo.
AB  - Antropyloroduodenal motility was recorded in seven anesthetized dogs to assess
      the role of nitric oxide and L-arginine metabolites in nonadrenergic
      noncholinergic (NANC) mediation of pyloric relaxation. Pyloric activity induced
      by duodenal field stimulation was inhibited by antral field stimulation and
      electrical vagal stimulation. Intra-arterial NG-L-arginine-methyl-ester (L-NAME)
      reduced the inhibition from antral or vagal stimulation (P less than 0.05).
      Intravenous infusion of L-NAME also blocked the inhibitory effect of vagal and
      antral stimulation but left the tetrodotoxin-insensitive action of intra-arterial
      vasoactive intestinal peptide (VIP) and sodium nitroprusside unchanged. L
      Arginine reversed the effect of L-NAME whereas D-arginine did not. L-NAME
      enhanced pyloric contractions to intra-arterial acetylcholine. The NANC
      inhibition of the substance P-stimulated pyloric response in vitro was blocked by
      L-NAME and reversed by addition of L-arginine. Sodium nitroprusside was effective
      as a relaxant in vitro but VIP was not. These data suggest that metabolites of L
      arginine mediate neural inhibition of canine pyloric motor activity.

PMID- 1348908
TI  - Calcitonin gene-related peptide: mechanisms of modulation of antral endocrine
      cells and cholinergic neurons.
AB  - Actions of human calcitonin-gene related peptide (hCGRP) on acetylcholine (ACh)
      discharge and gastrin and somatostatin release from rat antral mucosal-submucosal
      fragments were examined in both dynamic perifusion experiments and short-term
      static incubation studies. The principal findings of the dynamic perifusion
      experiments were that hCGRP exerted a dual or biphasic effect on ACh discharge
      and gastrin release. Initial exposure of antral tissues to hCGRP (1 x 10(-8) M)
      resulted in stimulation of both ACh and gastrin release that was of brief
      duration. Continued hCGRP perifusion caused subsequent inhibition of ACh and
      gastrin release that was substantially greater in duration and magnitude than the
      initial stimulatory responses. Static incubation studies indicated that hCGRP
      (10(-10) to 10(-7) M) stimulated somatostatin and inhibited gastrin release in a
      dose-dependent manner. Inhibition of gastrin and ACh release by hCGRP appeared to
      be an indirect effect that was mediated by somatostatin as suggested by studies
      with pertussis toxin (200 ng/ml). Furthermore, studies with atropine (1 x 10(-6)
      M) and tetrodotoxin (1 x 10(-6) M) indicated that CGRP-induced stimulation of
      somatostatin release and inhibition of ACh discharge occurred independent of
      muscarinic receptor activation and nerve excitation. In conclusion, results of
      these studies indicate that CGRP is capable of exerting both stimulatory and
      inhibitory effects on ACh release from mucosal-submucosal neurons and gastrin
      release from antral mucosal G cells in in vitro studies. These data suggest that
      the inhibitory effects of CGRP on cholinergic discharge and gastrin release are
      due to the paracrine effects of somatostatin released from antral D cells by
      direct action of CGRP.

PMID- 1348909
TI  - Role of gastrin, histamine, and acetylcholine in the gastric phase of acid
      secretion in anesthetized rats.
AB  - To determine the relative contributions of gastrin, histamine, and cholinergic
      stimulation to the gastric phase of acid secretion, peptone-stimulated acid
      output was measured in urethan-anesthetized pylorus-ligated rats after
      intravenous administration of gastrin monoclonal antibody, cimetidine, and
      atropine. Intragastric peptone stimulated acid secretion four-fold over basal,
      which was associated with a significant increase in plasma gastrin levels.
      Gastrin immunoneutralization and simultaneous H2- and muscarinic-receptor
      blockade demonstrated that approximately 40% of peptone-stimulated acid output as
      attributed to endogenous gastrin through a histamine-dependent pathway, whereas
      20% of acid output was accounted for by a cholinergic component. Another 10% of
      titratable acid was omeprazole-insensitive and presumably due to intragastric
      digestion of peptone. Therefore, approximately 30% residual acid output in
      response to peptone could not be accounted for by known acid stimulatory
      mechanisms. In rats given somatostatin monoclonal antibody to block the tonic
      inhibitory effect of endogenous somatostatin, residual acid output was a similar
      fraction of meal-stimulated acid output. In contrast, gastric distension induced
      by intragastric instillation of saline stimulated acid secretion to 1.5-fold over
      basal. Although 60% of distension-induced acid secretion could be inhibited by
      either H2 blockade or gastrin immunoneutralization, acid output returned to basal
      levels after simultaneous muscarinic blockade. These results indicate that
      gastrin, through a histaminergic pathway, is the principal mediator of meal
      stimulated acid secretion in anesthetized rats. Approximately 30% of acid output
      was due to other unidentified mechanisms, such as chemical secretagogues, a
      direct effect of amino acids, or novel peptides.

PMID- 1348910
TI  - Myocardial function in immature and mature sheep with pressure-overload
      hypertrophy.
AB  - The effect of pressure-overload left ventricular hypertrophy (LVH) on myocardial
      function is controversial. A major factor in the controversy may be the age at
      which the pressure overload was induced. The goal of this study was to determine
      whether the age at which the LVH was induced affected systolic myocardial
      function. We studied lambs (n = 8) and sheep (n = 7) with LVH induced by
      constricting the ascending aorta and their sham-operated controls (n = 7 and n =
      7). This new, unsedated, ovine model of LVH was large enough to accommodate
      chronic surgical implantation of instrumentation and the induction of pressure
      overload hypertrophy in both young and adult age groups. Solid-state
      intraventricular pressure transducers and sonomicrometer crystal were used to
      assess instantaneous left ventricular pressure and dimensions. Myocardial
      contractility was assessed with midwall shortening at common preload and
      afterload. Load alterations were induced by graded infusion of methoxamine. There
      was depressed myocardial function in adult sheep with LVH compared with adult
      controls. Lambs with and without LVH had normal left ventricular myocardial
      function, similar to adult controls. Similar results were obtained in studies
      after beta-adrenergic receptor blockade. We conclude that maturation decreases
      the ability of the myocardium to maintain normal contractility in the presence of
      pressure-overload hypertrophy.

PMID- 1348911
TI  - Effects of a coronary alpha 1-constriction on transmural left ventricular flow
      and contractile function.
AB  - Modulation of myocardial contractile function and perfusion by alpha 1-adrenergic
      receptors were examined in anesthetized dogs during left stellate ganglion
      stimulation. In 11 dogs, stellate stimulation significantly increased heart rate,
      mean arterial pressure, left ventricular systolic pressure, maximal rate of left
      ventricular pressure generation, segmental shortening and rate of shortening in
      anterior and posterior ventricular regions, and myocardial oxygen extraction.
      Myocardial lactate extraction decreased. The selective alpha 1-adrenergic
      antagonist prazosin (0.5 mg) injected into the circumflex artery during stellate
      stimulation caused significant additional increases in maximal rate of left
      ventricular pressure generation by 19 +/- 5% and in rate of shortening in
      posterior subendocardium by 20 +/- 6%. No changes were observed in posterior
      subepicardial or anterior subendocardial segmental contractile function.
      Myocardial oxygen and lactate extractions returned to their control values
      following prazosin injection. Regional left ventricular perfusion was measured
      using tracer microspheres in five additional dogs. Stellate stimulation increased
      subepicardial and subendocardial perfusion by 30%. Prazosin increased both
      subepicardial and subendocardial perfusion by an additional 36%. Stellate
      stimulation increased norepinephrine concentration in the coronary sinus, but no
      further increase was noted after blockage of alpha 1-receptors by prazosin. Thus,
      during sympathetic stimulation, an alpha 1-vasoconstriction existed uniformly
      across the left ventricular wall. However, blockade of this vasoconstriction was
      associated with an increase in contractile function only in the deeper muscle
      layers.

PMID- 1348912
TI  - Hypothalamic excitatory amino acid receptors mediate stress-induced tachycardia
      in rats.
AB  - The role of hypothalamic excitatory amino acid (EAA) receptors in mediating the
      cardiovascular response to stress was examined using conscious chronically
      instrumented rats. Microinjection of the EAA agonists N-methyl-D-aspartic acid
      (NMDA; 1-10 pmol), alpha-amino-3-hydroxy-5-methyl-4-isooxazolepropionic acid
      (AMPA; 0.3-3.0 pmol), or kainic acid (0.1-1.0 pmol) into the dorsomedial
      hypothalamus (DMH) elicited dose-related increases in heart rate and modest
      elevations in arterial pressure. Local microinjection of the NMDA antagonist 2
      amino-5-phosphonopentanoic acid (AP5; 100 pmol) selectively blocked NMDA-induced
      cardiovascular changes, whereas the non-NMDA EAA antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX; 50 pmol) selectively blocked the responses to
      AMPA and kainic acid. In the stress trials, microinjection of the nonselective
      EAA antagonist kynurenic acid (1-10 nmol) into the DMH blocked air stress-induced
      tachycardia in a dose-related manner. Similar injection of kynurenic acid at
      sites lateral or posterior to the DMH or injection of xanthurenic acid (a
      structural analogue of kynurenic acid with no antagonistic properties at EAA
      receptors) into the DMH failed to influence air stress-induced cardiovascular
      changes. Injection of either AP5 or CNQX into the DMH at doses shown to be
      selective for their respective EAA receptor subtypes also attenuated air stress
      induced tachycardia. Thus activity at EAA receptors in the DMH appears to be
      necessary for the generation of stress-induced changes in heart rate.

PMID- 1348913
TI  - Large-cell acanthoma. A distinctive keratosis.
AB  - Large-cell acanthoma is an epidermal neoplasm that is clinically, histologically,
      and biologically distinctive. Clinically, it differs from solar lentigo by being
      frequently skin-colored or hypopigmented. Histologically, it is defined by a
      population of uniformly large keratinocytes; it differs from solar lentigo by the
      absence of elongated hyperpigmented and sometimes hockey stick-shaped buds of
      keratinocytes. Biologically, it consists of hyperploid keratinocytes, whereas
      solar lentigo consists of diploid keratinocytes. Although the exact nosologic
      status of this entity is still controversial, its features are distinctive enough
      for the term "large-cell acanthoma" to merit continued usage.

PMID- 1348914
TI  - Betamethasone-induced resistance to neuromuscular blockade: a comparison of
      atracurium and vecuronium in vitro.
AB  - Steroids induce resistance to neuromuscular blocking drugs. Betamethasone-induced
      resistance to vecuronium has been demonstrated in vitro, and a presynaptic site
      of interaction has been suggested. This study investigated whether atracurium is
      similarly affected. Rat phrenic nerve-hemidiaphragm preparations were bathed in a
      physiologic solution, and one-half were exposed to betamethasone (1 mumol/L).
      Dose responses were recorded for atracurium (8-13 mumol/L) and vecuronium (2-12
      mumol/L) for control and betamethasone-treated preparations. In comparison to
      control, the betamethasone groups had significantly less depression of muscle
      contraction force at all concentrations of atracurium (P = 0.0004) and vecuronium
      (P = 0.002). The calculated ED50 (50% depression of muscle contraction force,
      expressed as mean +/- SEM) for atracurium was 8.83 +/- 0.62 mumol/L for controls
      and 11.19 +/- 0.54 mumol/L for betamethasone-treated preparations. The calculated
      ED50 for vecuronium was 4.72 +/- 0.41 mumol/L for controls and 6.84 +/- 0.66
      mumol/L for betamethasone-treated preparations. Betamethasone therefore increased
      the ED50 for atracurium by 27% and vecuronium by 45%; however, the magnitudes of
      these differences were not significant (P = 0.74) between the neuromuscular
      blocking agents. These results indicate that betamethasone-induced resistance to
      nondepolarizing neuromuscular blockade affects both atracurium and vecuronium to
      similar degrees in vitro.

PMID- 1348915
TI  - Is intravenous esmolol an acceptable substitute for an inadequate anesthetic?

PMID- 1348916
TI  - The antihypertensive and cardiac hemodynamic effects of nebivolol.
AB  - Acute, subacute, and chronic treatment with nebivolol, a novel beta 1-selective
      adrenergic antagonist, significantly lowered systolic and diastolic blood
      pressure and heart rate in patients with essential hypertension. No orthostatism
      and bradycardia were reported. A comparison between a normal control group and 23
      hypertensive patients revealed that the ratio between the preejection period
      (PEP) and the left ventricular ejection time (LVET) of the systolic time
      intervals (STI) was significantly increased in the hypertensive patients, owing
      to a prolongation of the PEPc (PEP corrected for heart rate). Treatment with
      nebivolol 5 mg once a day significantly improved the PEP/LVET, in acute
      conditions from 0.42 +/- 0.023 to 0.39 +/- 0.018, after one month of treatment
      from 0.40 +/- 0.013 to 0.36 +/- 0.013 and after one year of treatment from 0.41
      +/- 0.012 to 0.36 +/- 0.010, owing to a significant shortening of the PEPc. There
      was no correlation between changes of blood pressure and changes of STI.
      Diastolic dysfunction is an early finding in hypertension and may well be
      reflected in the prolongation of the PEPc. The improvement of left ventricular
      performance, as measured with STI, suggests that treatment with nebivolol may
      favorably influence the underlying diastolic dysfunction and be of therapeutic
      value for hypertensive patients with left ventricular damage.

PMID- 1348917
TI  - Takayasu's arteritis with collateral circulation from the right coronary artery
      to intracranial vessels--a case report.
AB  - A forty-four-year-old woman with Takayasu's arteritis and involvement of the
      aortic arch and its main branches complained of precordial pain on effort.
      Exercise electrocardiograms revealed significant ST segment depression in leads
      II, III, aVF, and V. Coronary arteriograms demonstrated no stenosis. However, the
      right coronary arteriogram revealed collateral circulation arising from the sinus
      node artery to the bilateral vertebral arteries and the left internal carotid
      artery. The collateral circulation was considered to be an important route of
      blood flow supply to the brain and, at the same time, a cause of coronary steal
      syndrome and, consequently, of angina pectoris.

PMID- 1348918
TI  - Cryptosporidium infection and CD4 counts.

PMID- 1348920
TI  - Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53)
      expression in squamous cell carcinomas of the lung. Clinical and biological
      correlations.
AB  - The expression of the protooncogene encoded proteins (c-erbB1, c-erb B2, c-myc, c
      fos) and the suppressor gene product p53 was analyzed in 81 human squamous cell
      carcinomas of the lung and correlated with clinical parameters of the patients
      (patient survival, presence of metastases and tumor stage) and with biological
      characteristics of the tumors (tumor growth in nude mice, DNA-ploidy,
      proliferative activity, drug-resistance and P-glycoprotein or gluathione S
      transferase expression). By means of immunohistochemistry, expression of c-erbB1
      oncoprotein (EGF-receptor) was detected in 79% of the tumors, c-erbB2 (c-neu)
      proteins in 35%, c-myc proteins in 48%, c-fos proteins in 41%, and p53 in 43% of
      the tumors. Patients with c-erbB1 positive tumors had a poor prognosis (p =
      0.021). In addition, these tumors were more frequently drug resistant (p =
      0.0067). A significant correlation between the growth of the squamous lung
      carcinomas in nude mice and c-fos oncoprotein expression was demonstrated (p =
      0.017). Therefore, EGF-receptor and c-fos products may serve as prognostic
      factors for the aggressiveness of squamous cell carcinomas of the lung and for
      the response of these tumors to chemotherapy. No significant correlation was
      found between the expression of the c-erbB1 or c-fos gene products and stage,
      metastasis and DNA-ploidy. In contrast to these results, no relationship was
      found between c-neu or c-myc gene products expression and any of the clinical or
      biological parameters examined. Aneuploid squamous cell carcinomas of the lung
      expressed p53 more frequently than diploid tumors (p = 0.027). However, there was
      no significant difference between p53 expression and stage, survival of patients,
      metastasis, growth of the tumors in nude mice, proliferative activity and drug
      resistance of the tumors.

PMID- 1348919
TI  - The differential reactivity of cells of the melanocytic lineage with four
      monoclonal antibodies against IFN-gamma inducible molecules.
AB  - The reactivity of four monoclonal antibodies (MAbs) directed against IFN-gamma
      inducible antigens with melanocytic cells was investigated in the course of local
      and systemic tumor progression of human malignant melanoma. Frozen sections of
      histologically defined melanocytic tissues at different stages of progression
      were stained with these MAbs using an indirect immunoperoxidase technique. The
      reactivity of MAbs Me15/B3 and Me15/F9, directed against two different epitopes
      of a 90-kDa molecule, was found to correlate with melanoma progression. Indeed, a
      significantly lower percentage of small than of advanced primary melanomas or
      metastases stained positively. A differential staining of nevocytic and
      dysplastic nevi was further observed for these two MAbs, which were also non
      reactive with normal skin melanocytes. The reactivity of MAb Me14/D12, which
      identifies the intercellular adhesion molecule ICAM-1 and MAb Mel14/F12, directed
      against a 40-kDa molecule, was found to be independent of the Breslow thickness
      of primary melanomas. Both the latter MAbs stained a high proportion of nevocytic
      and dysplastic nevi. The co-expression of the surface molecules defined by MAbs
      Me14/D12, Me15/B3 and Me15/F9 in the course of melanoma progression was also
      analyzed. The frequency of this co-expression increased according to the Breslow
      thickness of primary melanomas. In addition, up to 100% of metastases, as opposed
      to 20% of dysplastic nevi, were found to be simultaneously stained by these three
      MAbs. It is therefore conceivable that high-risk melanocytic lesions might be
      identified by the use of a combination of MAbs directed against IFN-gamma
      regulated antigens.

PMID- 1348921
TI  - Lack of expression of P-glycoprotein in 7 small cell lung cancer cell lines
      established both from untreated and from treated patients.
AB  - The establishment and characterisation of 7 small cell lung cancer cell lines is
      described. Four cell lines were established from biopsies taken from untreated
      patients and one of these was from primary tumour taken via the fibreoptic
      bronchoscope. The other three were from biopsies taken from patients who had
      relapsed after chemotherapy. All grow as non-adherent aggregates of cell and
      express a range of neuroendocrine and epithelial features characteristics of
      small cell lung cancer cell lines. No relationship was observed between the
      characteristics of the cell line in vitro and the treatment status of the patient
      from whom the biopsy was taken. Furthermore, none of the cell lines expressed p
      glycoprotein even though 3 were derived from relapse biopsies where chemotherapy
      included drugs associated with the multidrug resistance phenotype.

PMID- 1348922
TI  - [Embryonal carcinoma in the cryptorchid testis: apropos a case].
AB  - We report a case of testicular embryonal carcinoma in a patient with bilateral
      cryptorchidism. The diagnostic and therapeutic aspects of this disease entity are
      discussed. Although scrotal ultrasound constitutes an effective diagnostic
      method, it does not provide pathognomonic images that permit determining tumor
      histology as shown in the present case. Treatment of this tumor type depends on
      the degree of tumor spread: for stage I: inguinal orchidectomy and stage II:
      orchidectomy+lymphadenectomy. The need for adjuvant chemotherapy in these cases
      is discussed. In our view, it must depend on each specific case.

PMID- 1348923
TI  - Electroencephalographic sleep abnormalities in schizophrenia. Relationship to
      positive/negative symptoms and prior neuroleptic treatment.
AB  - Polysomnographic abnormalities in schizophrenia are not well characterized and
      their associations with schizophrenic symptomatology have not been adequately
      assessed. To address these issues, we recorded electroencephalographic sleep in
      20 drug-naive schizophrenics, 20 drug-free but previously medicated
      schizophrenics, and 15 normal controls. Drug-naive and previously medicated
      patients had significantly greater impairment of sleep continuity and shorter
      rapid eye movement latency when compared with controls. In the previously
      medicated group, findings were significantly influenced by duration of drug-free
      status. Rapid eye movement latency was inversely correlated with the severity of
      negative symptoms (r = -.52) but was unrelated to depressive symptoms. Slow-wave
      sleep did not differ between schizophrenic patients and normal controls and was
      unrelated to any clinical parameter. Mechanisms underlying the observed
      associations between rapid eye movement sleep abnormalities and negative symptoms
      in the acute phase of schizophrenic illness need to be explored.

PMID- 1348924
TI  - Exclusion of linkage between the serotonin2 receptor and schizophrenia in a large
      Swedish kindred.
AB  - Family, twin, and adoption studies suggest that genetic factors play an important
      role in the etiology of schizophrenia. Detection of single gene(s) involved in a
      higher susceptibility to a hereditary disease is possible with linkage analysis.
      The effects of serotonin2-receptor antagonists on symptoms of schizophrenia
      suggest that a mutation in the gene coding for this receptor subtype might be
      involved in the pathophysiology of this disease. Recently a copy DNA encoding the
      serotonin 5-HT2 receptor has been isolated and with a human 5-HT2 receptor copy
      DNA probe the HTR2 locus has been mapped to chromosome 13. Using multipoint
      linkage analysis between schizophrenia and genetic markers spanning the region of
      the HTR2 locus, we were able to exclude linkage between this candidate gene and
      schizophrenia in a Swedish kindred. Given this result, we conclude that the
      serotonin 5-HT2 receptor gene itself is not a major susceptibility gene for
      schizophrenia in this family.

PMID- 1348925
TI  - Glucose attenuation of paradoxical sleep deficits in old rats.
AB  - Glucose administration enhances memory in several amnestic populations, including
      old humans and rodents. The present experiment demonstrates that glucose also
      enhances measures of sleep in old rats. Three-hour day-time sleep EEGs were
      assessed in 3- and 24-month-old rats. The animals received injections of saline
      or glucose (100, 500, and 1000 mg/kg) on different days in a counter-balanced
      order. At doses of 100 and 500 mg/kg, glucose augmented the duration of
      paradoxical sleep bouts and total paradoxical sleep time in old, but not young,
      rats. Within 2 weeks after the sleep tests, measures of several brain
      neurotransmitter functions were obtained. Glucose was more effective in enhancing
      paradoxical sleep in those individual aged rats with high levels of hippocampal
      choline acetyltransferase and occipital cortex serotonin concentrations than in
      aged rats with lower levels on these neurochemical measures. The findings suggest
      that glucose attenuates selective age-related sleep deficits in old rats. More
      generally, these results add to a growing body of evidence indicating that
      moderate doses of peripheral glucose can influence a variety of CNS measures.

PMID- 1348926
TI  - Regulation of cardiac adenylate cyclase activity in rodent models of obesity.
AB  - We have investigated beta-adrenergic regulation of adenylate cyclase activity in
      heart tissue membranes from the genetically obese Zucker rat, the genetically
      obese CBA mouse and the genetically obese diabetic (db/db) mouse. Responsiveness
      to beta-adrenergic stimulation was impaired in membranes from the obese Zucker
      rat, but not in the other models. The membranes from obese Zucker rats showed
      both decreased beta-adrenergic-receptor number and altered coupling between beta
      adrenergic receptors and the stimulatory guanine-nucleotide-binding protein, Gs.
      In contrast, no alterations in either the levels of Gs or the functional
      interaction between this protein and the catalytic moiety of adenylate cyclase
      were observed. In these three genetic models of obesity we observe dissimilar
      alterations in the control of adenylate cyclase.

PMID- 1348927
TI  - Regulation of the expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA
      synthase gene. Its role in the control of ketogenesis.
AB  - We have explored the role of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG
      CoA) synthase in regulating ketogenesis. We had previously cloned the cDNA for
      mitochondrial HMG-CoA synthase and have now studied the regulation in vivo of the
      expression of this gene in rat liver. The amount of processed mitochondrial HMG
      CoA synthase mRNA is rapidly changed in response to cyclic AMP, insulin,
      dexamethasone and refeeding, and is greatly increased by starvation, fat feeding
      and diabetes. We conclude that one point of ketogenic control is exercised at the
      level of genetic expression of mitochondrial HMG-CoA synthase.

PMID- 1348929
TI  - Cross-talk between M2 muscarinic and D1 dopamine receptors in the cat adrenal
      medulla.
AB  - In the study reported here we have reached two conclusions. First, the cat
      adrenal medulla chromaffin cell possesses a dopamine D1 receptor that seems to be
      coupled to an adenylyl cyclase. Second, this receptor regulates the muscarinic
      mediated catecholamine release response through a negative feed-back loop which
      uses cyclic AMP as a second messenger. These conclusions are supported by the
      following findings: (i) SKF38393 (a selective D1 receptor agonist), but not
      quinpirole (a selective D2 agonist), inhibits the methacholine-mediated
      catecholamine release responses in a concentration-dependent manner (IC50 of
      around 1-2 microM). (ii) SCH23390 (a selective D1 antagonist), but not sulpiride
      (a selective D2 antagonist), reversed by 70% the inhibitory effects of SKF38393.
      (iii) Dibutyril cyclic AMP (500 microM) inhibited by 80% the secretory effects of
      methacholine.

PMID- 1348928
TI  - Coenzyme A is a potent inhibitor of acetyl-CoA carboxylase from rat epididymal
      fat-pads.
AB  - Rat epididymal fat-pad extracts have previously been shown to contain an insulin
      stimulated acetyl-CoA carboxylase kinase, which is co-eluted from Mono Q ion
      exchange chromatography with a potent inhibitor of acetyl-CoA carboxylase
      [Borthwick, Edgell & Denton (1990) Biochem. J. 270, 795-801]. A variety of tests,
      including reactivity with thiol reagents, identify this inhibitor as CoA.
      Inhibition requires the presence of MgATP, but is independent of any
      phosphorylation of the enzyme. The effect is complete in about 5 min and is
      associated with depolymerization of acetyl-CoA carboxylase. Half-maximal
      inhibition is observed at about 40 nM-CoA. The inhibitory effects of CoA can be
      partially reversed by incubation with citrate and more fully overcome by
      treatment of the enzyme with the insulin-stimulated acetyl-CoA carboxylase
      kinase.

PMID- 1348930
TI  - Lineage and stage specific expression of HOX 1 genes in the human hematopoietic
      system.
AB  - Recent observations have demonstrated the expression of several members of the
      homeobox-containing (HOX) gene complexes within the hematopoietic compartment. We
      have analyzed the expression pattern of the entire HOX 1 locus in a panel of
      leukemia-derived human cell lines representing various blood phenotypes. The
      expression of the eleven HOX 1 genes is lineage-restricted and these genes are
      predominantly detected within cells of myelomonocytic origin. This is in strong
      contrast with the erythro-megakaryocytic specific expression of HOX 2 genes.
      Furthermore, we have observed that the expression of three HOX 1 genes within B
      lymphoid lineages is stage-related and that the expression of several of them is
      switched off during TPA-induced differentiation of Kg1 and U937. These
      observations suggest that HOX 1 homeoproteins could be regulators of lineage
      determination during hematopoiesis.

PMID- 1348931
TI  - Mutations in the P53 tumour suppressor gene in primary lung cancer in Japan.
AB  - The reverse transcription-polymerase chain reaction-single strand conformation
      polymorphism (RT-PCR-SSCP) analysis and sequencing were used to examine p53 gene
      alterations in 18 surgical specimens of primary lung cancers obtained in Japan.
      Somatic mutations resulting in amino acid changes were found in eight of the 18
      cases (44%). Seven missense mutations were located in amino acid-conserved
      domains or their vicinities (codons 110 to 307). Most mutations were found at G-C
      pairs, suggesting that specific carcinogens are involved in the etiology of lung
      cancer. The p53 mutations showed a significant association with a history of
      smoking (P = 0.0294). We suggest that the p53 mutations may be associated with
      smoking-induced lung carcinogenesis.

PMID- 1348932
TI  - Genomic differences between O6-methylguanine-DNA methyltransferase proficient
      (Mex+) and deficient (Mex-) cell lines: possible role of genetic and epigenetic
      changes in conversion of Mex+ into Mex-.
AB  - Cell lines that possess O6-methylguanine-DNA methyltransferase (MGMT) repair
      activity (Mex+ phenotype) or are deficient for MGMT (Mex-) are compared at
      genomic level. It is shown that 1) 208F rat cells do not contain the MGMT gene,
      as detected by Southern blot hybridization. 2) Mex- HeLa MR and CHO-9 cells
      express very low amounts of MGMT mRNA, as detected by PCR. The size of the MGMT
      specific PCR product was slightly smaller than that generated from Mex+ HeLa S3
      cells. 3) HeLa MR, compared to various human Mex+ cell lines, shows a restriction
      fragment length polymorphism indicating mutational alteration of MGMT gene
      sequences. 4) Mex- cells (HeLa MR) and cells that express very low MGMT activity
      (GM637) exhibit hypomethylation of the MGMT gene as revealed by MspI/HpaII
      restriction digests. 5) Exposure of Mex- cells to 5-azacytidine and selection
      with N-hydroxyethyl-N-chloroethylnitrosourea (HeCNU) did not yield Mex+
      revertants. With V79 cells treated with 5-azacytidine clones resistant to HeCNU
      were isolated. These cells were MGMT deficient and not cross-resistant to N
      methyl-N'-nitro-N-nitrosoguanidine indicating the existance of a defence
      mechanism other than MGMT against chloroethylating agents. The data suggest down
      regulation of MGMT transcription accompanied by decreasing CpG methylation, but
      in some cell lines also mutational alterations to be involved in extinction of
      the Mex+ phenotype.

PMID- 1348933
TI  - Apolipoprotein B genetic polymorphisms in several human hepatoma derived liver
      cell lines.
AB  - The genetic polymorphism of apoB EcoRI and XbaI restriction sites and the 3' VNTR
      hypervariable region was examined in nine human hepatoma derived liver cell lines
      and related to the cells' ability to secrete lipids and apoB. EcoRI and XbaI
      genotypes appeared to be unrelated to triglyceride, cholesterol and apoB
      accumulating in the medium. The VNTR consisted of alleles with 47 to 67 repeats;
      however, these repeats were not associated with elevated concentrations of lipid
      or apoB. Data suggest that in the hepatoma cell lines, apoB polymorphisms in
      EcoRI, XbaI and the VNTR hypervariable region are not sufficient in themselves to
      account for triglyceride, cholesterol and apoB in the medium. It is possible that
      intracellular apoB synthesis and/or degradation as well as postsecretory apoB
      binding and uptake are responsible for the variability of apoB and lipid
      accumulation in the culture medium.

PMID- 1348934
TI  - Partial amino acid sequence of a somatostatin receptor isolated from GH4C1
      pituitary cells.
AB  - A somatostatin receptor isolated from GH4C1 rat pituitary tumor-derived cells was
      cleaved with cyanogen bromide or cyanogen bromide+trypsin to obtain sequenceable
      fragments. Five unique amino acid sequences ranging from 6 to 27 amino acid
      residues were obtained. The sequence was identical to sequence recently reported
      for one of two somatostatin receptors cloned from human pancreas [Yamada et al.,
      (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 251-255] except for a single valine to
      isoleucine substitution. This is the first report of amino acid sequence from a
      purified somatostatin receptor.

PMID- 1348935
TI  - ADPRibosylation of chicken red cell tubulin and inhibition of microtubule self
      assembly in vitro by the NAD(+)-dependent avian ADPRibosyl transferase.
AB  - Chicken erythrocyte tubulin was found to undergo NAD(+)-dependent ADPribosylation
      in vitro in the presence of ADPRtransferase also isolated from avian red blood
      cells. Unlike the low level of ADPR incorporation catalyzed by Cholera and
      Pertussis toxins (i.e., less than 0.005 mol ADPR/mol tubulin), the avian system
      displayed a much higher stoichiometry of 0.8-1.2 mol ADPR/mol tubulin.
      Modification resulted in potent inhibition of microtubule self-assembly, even in
      the presence of bovine brain microtubule-associated proteins or with the addition
      of pre-assembled microtubules.

PMID- 1348936
TI  - Piperine-mediated changes in the permeability of rat intestinal epithelial cells.
      The status of gamma-glutamyl transpeptidase activity, uptake of amino acids and
      lipid peroxidation.
AB  - The effect of piperine (1-[5-(1,3-benzodioxol-5-yl)-1-oxo-2,4
      pentadienyl]piperidin e), (from Piper nigrum) on the absorptive function of the
      intestine was studied. In vitro experiments showed that piperine (25-100 microM)
      significantly stimulated gamma-glutamyl transpeptidase (gamma-GT, EC 2.3.2.2.)
      activity, enhanced the uptake of radiolabelled L-leucine, L-isoleucine and L
      valine, and increased lipid peroxidation in freshly isolated epithelial cells of
      rat jejunum. The kinetic behaviour of gamma-GT towards substrate and acceptor
      altered in the presence of piperine. In the presence of benzyl alcohol, an
      enhanced gamma-GT activity due to piperine was maintained. These results
      suggested that piperine may interact with the lipid environment to produce
      effects which lead to increased permeability of the intestinal cells.

PMID- 1348937
TI  - Drug transport, viability and morphology of isolated rat hepatocytes preserved
      for 24 hours in University of Wisconsin solution.
AB  - Isolated hepatocytes are a valuable tool to study liver functions. Suitable
      methods to preserve the isolated cells with good maintenance of viability and
      functions are crucial to extend experiments with hepatocytes from a single
      isolation over 2 or more consecutive days. We investigated whether University of
      Wisconsin (UW) solution, which was designed to preserve organs for
      transplantation, is also suitable for preservation of isolated rat hepatocytes.
      Viability, as determined by Trypan blue exclusion and reduction of the
      tetrazolium 3(4,5-dimethyl-thiazoyl-2-yl)2,5 diphenyltetrazolium bromide to a
      purple formazan, morphological appearance using electron microscopy, ATP levels
      and uptake and storage of three model drugs ([3H]vecuronium, [3H]taurocholic acid
      and [3H]ouabain) were determined directly after isolation and after 22 hr of
      storage in UW solution at 0-4 degrees. The present study shows that cold storage
      of rat hepatocytes for 22 hr in UW can be performed without significant loss of
      viability and with maintenance of proper morphology, cellular ATP and transport
      functions. In contrast, after storage in Krebs-Henseleit buffer the normal
      morphology, ATP content and transport functions were strongly affected. These
      results imply that hepatocytes from a single isolation and stored in UW solution
      can be used for experiments on 2 consecutive days.

PMID- 1348938
TI  - Differences in T cell receptor restriction fragment length polymorphisms in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: The purpose of this study was to determine whether a T cell receptor
      (TCR) polymorphism, either by itself or in combination with particular HLA
      polymorphism, leads to susceptibility to rheumatoid arthritis (RA). METHODS:
      Eight restriction fragment length polymorphisms (RFLPs) detected with TCR gene
      segments were investigated in 46 individuals with RA and were compared with data
      from normal control subjects. RESULTS: A statistically significant difference in
      the genotype frequencies of a Taq I RFLP detected with the TCR alpha constant
      region (C alpha) gene was noted. In addition, when the DR4+ subpopulations were
      examined, the allelic frequency of a 2-kb Bam HI fragment detected with a V beta
      8 gene was increased in the samples from RA patients (P less than 0.0086).
      CONCLUSION: The results of this study suggest that germline differences in the
      TCR repertoire may be associated with RA, and that there is a contributory effect
      of DR4+ haplotypes with certain TCR haplotypes in susceptibility to RA.

PMID- 1348939
TI  - Magnetic resonance imaging detection of aortic and pulmonary artery wall
      thickening in the acute stage of Takayasu arteritis. Improvement of clinical and
      radiologic findings after steroid therapy.
AB  - OBJECTIVE: Early diagnosis of Takayasu arteritis in the acute stage (prepulseless
      stage) is extremely difficult. Identification of a useful approach to detecting
      the initial changes of arteritis is therefore desirable. METHODS: Careful
      clinical examination of a young woman with persistent fever and dry cough
      revealed faintly audible bruits at the cervical, supraclavicular, and abdominal
      regions. Aortographic features suggested thickening of the wall of the descending
      thoracic aorta. Magnetic resonance imaging (MRI) of this area was diagnostic.
      RESULTS: MRI demonstrated involvement of the ascending aorta and right main
      pulmonary artery. Steroid therapy (prednisolone 60 mg/day) induced dramatic
      clinical and radiologic improvement in 2 months. CONCLUSION: This is the first
      report of MRI-documented reduction in the thickness of the walls of both the
      aorta and the pulmonary artery following steroid therapy.

PMID- 1348940
TI  - Production of peptide hormones and neurotransmitters by the immune system.

PMID- 1348941
TI  - Signaling pathways of the neuroendocrine-immune network.

PMID- 1348942
TI  - Role of glutathione peroxidase in rheumatoid arthritis: analysis of enzyme
      activity and DNA polymorphism.
AB  - Aberrant expression of the antioxidant enzyme glutathione peroxidase (GPx) could
      contribute to the etiology of rheumatoid arthritis (RA). However, previous enzyme
      activity studies examining this relationship were inconclusive. Indirect evidence
      for this relationship derives from the known efficacy of gold therapy in RA,
      since gold compounds specifically inhibit GPx. The hypothesis that variants of
      GPx are associated with RA was examined by two approaches: enzyme activity
      analysis and restriction fragment length polymorphism (RFLP) association
      analysis. No significant difference was found in whole blood GPx activity between
      28 RA patients and 36 controls. GPx activity appeared to be independent of sex,
      race, or type of drug treatment. However, a statistically significant difference
      was found with respect to treatment responsiveness. RA patients classified as
      good responders to gold therapy, but who were no longer taking gold, had a
      significantly higher GPx activity compared to both the controls and good
      responders currently on gold therapy. Aberrantly high GPx activity could
      contribute to RA by generating excess oxidized glutathione, a potent collagenase
      activator. Gold therapy would reduce GPx activity to normal levels. The
      restriction enzyme Pvu II in conjunction with a GPx gene probe identified a
      useful RFLP (Al, 22 kbp; A2, 15 kbp) with allelic frequencies of A1 and A2 equal
      to 0.11 and 0.89, respectively, in the control population. No statistically
      significant association, however, could be demonstrated between this allelic
      variant of the GPx gene and RA.

PMID- 1348943
TI  - Correlation between kinetics of soluble CD4 interactions with HIV-1-Env
      expressing cells and inhibition of syncytia formation: implications for
      mechanisms of cell fusion and therapy for AIDS.
AB  - OBJECTIVES: To study the kinetics of the interactions between soluble (s) CD4 and
      HIV-1-Env-expressing cells in relation to subsequent events leading to cell
      fusion and inhibition of syncytia formation. DESIGN: Vaccinia-HIV-1 (Env)
      infected CD4- T-cells were used to study the kinetics of sCD4-gp120/41
      interactions and syncytia formation (with CD4+ T-cells) under identical
      conditions. METHODS: sCD4 association and dissociation rates for HIV-1-Env
      expressing cells, and quantification of sCD4-induced gp120 shedding was
      determined by a quantitative flow cytometry assay. Syncytia inhibition was
      measured in the continuous presence of sCD4, or after washing of HIV-1-Env
      expressing cells following pre-incubation with sCD4. RESULTS: The kinetics of
      syncytia inhibition correlated with sCD4 binding when sCD4 was maintained during
      the culture. When Env-expressing cells, which had been pre-incubated with sCD4,
      were washed to remove unbound sCD4, no syncytia formation inhibition was
      observed, even following sCD4-induced shedding of greater than 50% of surface
      gp120 molecules. CONCLUSIONS: The lack of syncytia inhibition seen after removal
      of unbound sCD4, even after pre-incubation of cells under saturation and gp120
      shedding conditions, indicated that sufficient numbers of fusogenic molecules
      remained on the sCD4-treated cells. In addition, fast dissociation of pre-bound
      sCD4 occurred in culture. These results are important for understanding HIV-1-Env
      mediated cell fusion and AIDS therapy.

PMID- 1348944
TI  - Clinical features and predictive markers of disease progression in cynomolgus
      monkeys experimentally infected with simian immunodeficiency virus.
AB  - OBJECTIVE: To study the pathogenicity of simian immunodeficiency virus (SIVsm) in
      cynomolgus monkeys in order to establish an animal model for human AIDS. METHODS:
      Thirty-three cynomolgus monkeys were monitored for more than 2 years following
      experimental infection with SIVsm. RESULTS: All the macaques became SIV-infected,
      as demonstrated by virus recovery from peripheral blood lymphocytes and by the
      appearance of viral antibodies. SIVsm was found to be pathogenic, killing 29 out
      of the 33 monkeys (88%) within 26 months. Clinically, infected monkeys developed
      lymphadenopathy, splenomegaly, diarrhoea, weight loss, neurological symptoms and
      a remarkably high incidence (39%) of malignant lymphomas. All lymphomas were high
      grade malignant and of B-cell origin. Disease progression was associated with low
      CD4+ lymphocyte count, involution of initially hyperplastic follicular B-cell
      areas in lymph nodes, reappearance of viral antigen in serum, loss of anti-Gag
      antibodies and development of systemic giant cell disease in 55% of the monkeys.
      CONCLUSIONS: There are many similarities between SIVsm-induced AIDS in cynomolgus
      monkeys and human AIDS with regard to clinical, virological, immunological and
      pathological manifestations.

PMID- 1348945
TI  - Impaired T-cell priming and proliferation in cats infected with feline
      immunodeficiency virus.
AB  - OBJECTIVE: Cats naturally infected with feline immunodeficiency virus (FIV) are
      particularly susceptible to infection with opportunistic pathogens, suggesting
      that these animals are unable to develop an effective immune response against the
      pathogen. Previous studies have used CD4+:CD8+ lymphocyte ratios and mitogen
      blastogenesis to identify immunological abnormalities in FIV-infected cats.
      However, these studies provide limited information for understanding the nature
      of the cellular dysfunction in FIV-infected cats, particularly defects in antigen
      specific immune responses. DESIGN: To investigate whether cats infected with FIV
      are less able to mount an immune response to previously unencountered antigens,
      we compared the development of antigen-specific cellular immunity at the stage of
      T-cell priming in uninfected and FIV-infected cats. INTERVENTIONS: The general
      immune status of cats was assessed by peripheral blood CD4+:CD8+ lymphocyte
      ratios (flow cytometry), and by lymphocyte blastogenesis response to T- and B
      cell mitogens. In addition, we describe the development of an autologous culture
      system to measure specific priming of naive feline T-cells to soluble antigen in
      vitro. This assay was used to compare T-cell priming in uninfected cats and cats
      which had been infected with FIV for 6-27 months. RESULTS: As in HIV infection,
      CD4+:CD8+ lymphocyte ratios in FIV-infected cats were found to be inverted, due
      to a reduction in the percentage of CD4+ cells. In addition, lymphocyte
      blastogenesis to both T- and B-cell mitogens was significantly impaired in FIV
      infected cats. Priming to keyhole limpet haemocyanin (KLH) elicited a late
      proliferative response resulting from the expansion of CD4+ (T-helper cells). T
      cell growth factor secretion correlated with cell proliferation. Restimulation of
      cells with fresh antigen-presenting cells and antigen showed that antigen
      specific T-cell priming had occurred in the initial culture. When primary
      proliferation responses in FIV-infected cats were examined, it was observed that
      naive CD4+ T-cells from FIV-infected cats were significantly impaired (P less
      than 0.001) in their ability to be primed to KLH when compared with uninfected
      controls. CONCLUSIONS: Impaired priming of naive CD4+ T-helper cells to antigen
      in FIV-infected cats may explain the increased susceptibility of these animals to
      infection by opportunistic pathogens. The poor ability of human patients with
      AIDS to develop humoral immunity following vaccination may also be caused by such
      a defect in T-cell priming.

PMID- 1348946
TI  - Diagnostic accuracy of three clinical case definitions for advanced HIV disease.
AB  - OBJECTIVE: To assess the accuracy of three clinical case definitions for advanced
      HIV disease: the World Health Organization (WHO) case definition, and the
      original and revised Caracas case definitions. DESIGN: Retrospective chart
      review. SETTING: A clinic for patients with all stages of HIV infection at the
      Johns Hopkins Hospital, Baltimore, [correction of Bethesda] Maryland, USA, a
      tertiary care university hospital. PATIENTS, PARTICIPANTS: Two hundred and twenty
      four HIV-positive adults who underwent initial evaluation between 1 January 1990
      and 31 December 1990. MAIN OUTCOME MEASURES: A score for each definition was
      assigned based on initial evaluation. The sensitivity, specificity, and
      predictive values were calculated using the Centers for Disease Control (CDC)
      staging criteria, and results were correlated with total CD4 cell counts.
      RESULTS: The sensitivities of the WHO, and the original and revised Caracas
      definitions were 40, 67, and 60%, respectively, using CDC disease stage IV as a
      positive standard. Specificities were between 99 and 100%, using CDC stage II-III
      disease as a negative standard. Mean CD4 cell counts for patients with positive
      scores were 184, 160, and 158 x 10(6)/l, respectively, compared to 191 x 10(6)/l
      for CDC stage IV patients. Sensitivity was lower when the positive standard was
      expanded to include all patients with CD4 cell counts less than 200 x 10(6)/l.
      CONCLUSIONS: In our study population, case definitions were specific, but only
      moderately sensitive for advanced HIV disease. Prospective studies should be
      conducted in diverse geographic regions, using lymphocyte or CD4 cell counts when
      possible.

PMID- 1348947
TI  - Progress of HIV infection and changes in the lipid membrane structure of CD4+
      cells.

PMID- 1348948
TI  - Distribution of tyrosine hydroxylase immunoreactive nerve fibers in the canine
      larynx.
AB  - The sympathetic innervation of the canine larynx was investigated using tyrosine
      hydroxylase (TH) immunohistochemistry. Many tyrosine hydroxylase immunoreactive
      (TH-IR) nerve fibers were observed around arteries and arterioles in the
      laryngeal mucosa and intrinsic laryngeal muscles. In the glandular region, TH-IR
      fibers were also found, with some of these fibers terminating around the basement
      membranes of the glandular cells. The quantity of TH-IR fibers in the mucosa
      differed among regions of the larynx. Many of these fibers could be found in the
      laryngeal surface of the epiglottis as well as the posterior glottis. These
      findings suggest that TH-IR fibers may directly innervate muscles in the
      intrinsic larynx.

PMID- 1348949
TI  - Developmental switch in the pharmacology of Ca2+ channels coupled to
      acetylcholine release.
AB  - The pharmacological specificity of Ca2+ channel-secretion coupling in
      acetylcholine (ACh) and somatostatin (SOM) release was studied in the chick eye
      choroid neuromuscular junctions and in dissociated ciliary ganglion (CG) neurons.
      ACh secretion changes in development from stage (St) 40, when release is
      dihydropyridine (DHP) and partially omega-conotoxin (omega-CgTX) sensitive, to
      posthatch, when release is insensitive to DHPs but sensitive to omega-CgTX. St 40
      CG neurons cultured with striated muscle have release properties similar to those
      of St 40 iris and choroid but different from those of St 34 neurons, which are
      neither DHP nor omega-CgTX sensitive. SOM (also coreleased from posthatch choroid
      terminals) can inhibit ACh release in both posthatch and St 40 choroids,
      suggesting that the SOM receptor interacts with both DHP-sensitive and 
      insensitive channels.

PMID- 1348950
TI  - Rostrocaudal polarity of the tectum in birds: correlation of en gradient and
      topographic order in retinotectal projection.
AB  - Rostrocaudal polarity of the tectum is first detectable at embryonic day 2 (E2)
      in the chick by the rostrocaudal gradient of en expression. When ectopic tectum
      is produced by heterotopic transplantation at E2 in the diencephalon, the
      gradient of en expression is inverted from the host polarity by environmental
      influences. Here we report that the retinal fibers project to the ectopic tectum
      in a topographic order in accord with the inverted gradient of en expression.
      Moreover, if ectopic tectum was produced at E3, when the en pattern was
      preserved, the retinotectal projection pattern was also in accord with the en
      pattern, suggesting that rostrocaudal polarity of retinotectal order follows en
      expression patterns.

PMID- 1348951
TI  - Inhibition of the omega-conotoxin-sensitive calcium current by distinct G
      proteins.
AB  - Leu-enkephalin (Leu-Enk), norepinephrine (NE), somatostatin (SS), and bradykinin
      (BK) decrease the voltage-dependent calcium current in NG108-15 cells. Here we
      have investigated whether distinct G proteins, or a G protein common to all of
      the pathways, mediates this inhibition. We found that pertussis toxin (PTX)
      reduced all of these transmitter actions, except that of BK. To examine which of
      the PTX-sensitive pathways is transduced by GoA, we constructed an NG108-15 cell
      line that stably expresses a mutant, PTX-resistant alpha subunit of GoA. After
      treatment with PTX, the mutant GoA alpha rescued the Leu-Enk and NE pathways but
      not the SS pathway. At least three different G proteins can transduce receptor
      mediated inhibition of calcium currents in nerve cells. The effects of these G
      proteins appear to converge on the omega-conotoxin GVIA-sensitive calcium
      current.

PMID- 1348952
TI  - A cell line with unusual characteristics from an ovarian carcinoma patient:
      modulation of sensitivity to antitumour drugs.
AB  - A cell line (GZL-8) was established by cloning from ascitic fluid of an untreated
      ovarian carcinoma patient. The cells grew rapidly, accumulated lipids and showed
      chromosomal alterations. One of the marker chromosomes showed characteristics of
      a Y-like chromosome. This unusual finding was confirmed by DNA hybridisation
      using specific probes to the Y chromosome. The cells stained with fluorescent
      antibodies to desmoplakin and cytokeratins 8, 18, 19, and weakly with vimentin
      but not with desmin. The presence of epithelial membrane antigen, human milk fat
      globulin, alpha-lactalbumin, alpha-fetoprotein, placental alkaline phosphatase
      and oestrogen receptor-related antigen was demonstrated by indirect
      immunoperoxidase staining, but no CA-125 antigen could be detected. The cells
      showed positive reaction with antibodies to P-glycoprotein. The function of the P
      glycoprotein transport system was demonstrated by the rhodamine-123 release test.
      The cells were initially responsive to doxorubicin, and to high concentrations of
      cisplatin. Growth inhibition by doxorubicin, especially at low doses was enhanced
      by the addition of verapamil or tamoxifen. This was shown by the soft agar
      clonogenic assay, by direct cell counting and by the MTT reducing test. Our
      results show that combination between drug and sensitivity modulators may be of
      potential clinical value in ovarian cancer.

PMID- 1348953
TI  - Identification and interpretation of epidermal growth factor and c-erbB-2
      overexpression.
AB  - Overexpression of normal cellular genes may be one mechanism by which malignant
      cells can acquire a selective growth advantage. The epidermal growth factor
      receptor and the c-erbB-2 protein are members of the erbB family and are good
      examples of genes that appear to act through this mechanism. Molecular and
      biochemical analyses of these two proteins also illustrate how studies of growth
      factors, growth factor receptors and oncogenic retroviruses may lead to new
      approaches to diagnosis and treatment. In particular, overexpression of these
      growth factor receptors has identified clinical subgroups that may respond
      differently to chemotherapy and provides the opportunity for antibody targeted
      therapy. Overexpression of these proteins can be identified using
      immunocytochemistry on both histological sections and fine-needle aspirates, thus
      enabling these parameters to be assessed preoperatively and to be monitored
      during therapy.

PMID- 1348954
TI  - Clinical trials referral resource. Clinical trials with taxol.

PMID- 1348955
TI  - [3. Conference for continuing education for pediatric nurses. Theme:
      Neuropediatrics].

PMID- 1348956
TI  - Conformational states of ribulosebisphosphate carboxylase and their interaction
      with chaperonin 60.
AB  - Conformational states of ribulosebisphosphate carboxylase (Rubisco) from
      Rhodospirillum rubrum were examined by far-UV circular dichroism (CD), tryptophan
      fluorescence, and 1-anilino-naphthalenesulfonate (ANS) binding. At pH 2 and low
      ionic strength (I = 0.01), Rubisco adopts an unfolded, monomeric conformation
      (UA1 state) as judged by far-UV CD and tryptophan fluorescence. As with other
      acid-unfolded proteins [Goto, Y., Calciano, L. J., & Fink, A. L. (1990) Proc.
      Natl. Acad. Sci. U.S.A. 87, 573-577], an intermediate conformation (A1 state) is
      observed at pH 2 and high ionic strength. The A1 state has an alpha-helical
      content equivalent to 64% of that present in the native dimer (N2 state).
      However, fluorescence measurements indicate that the tertiary structure of the A1
      state is largely disordered. A site-directed mutant, K168E, which exists as a
      stable monomer [Mural, R. J., Soper, T. S., Larimer, F. W., & Hartman, F. C.
      (1990) J. Biol. Chem. 265, 6501-6505] was used to characterize the "native"
      monomer (N1 state). The far-UV CD spectra of the N1 and N2 states are almost
      identical, indicating a similar secondary structure content. However, the
      tertiary structure of the N1 state is less ordered than that of the N2 state.
      Nevertheless, when appropriately complemented in vitro, K168E forms an active
      heterodimer. Upon neutralization of acid-denatured Rubisco or dilution of
      guanidine hydrochloride-denatured Rubisco, unstable folding intermediates (I1
      state) are rapidly formed. At concentrations at or below the "critical
      aggregation concentration" (CAC), the I1 state reverts spontaneously but slowly
      to the native states with high yield (greater than 65%). The CAC is temperature
      dependent. At concentrations above the CAC, the I1 and the A1 states undergo
      irreversible aggregation. The commitment to aggregation is rapid [ef. Goldberg,
      M. E., Rudolph, R., & Jaenicke, R. (1991) Biochemistry 30, 2790-2797] and
      proceeds until the concentration of folding intermediate(s) has fallen to the
      CAC. In the presence of a molar excess of chaperonin 60 oligomers, the I1 state
      forms a stable binary complex. No stable binary complex between chaperonin 60 and
      the N1 state could be detected. Formation of the chaperonin 60-I1 binary complex
      arrests the spontaneous folding process. The I1 state becomes resistant to
      interaction with chaperonin 60 with kinetics indistinguishable from those
      associated with the appearance of the native states. In vitro complementation
      analysis indicated that the product of the chaperonin-facilitated process is
      monomeric.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1348957
TI  - Promotion of the in vitro renaturation of dodecameric glutamine synthetase from
      Escherichia coli in the presence of GroEL (chaperonin-60) and ATP.
AB  - The folding and assembly of dodecameric glutamine synthetase (GS) from
      Escherichia coli was examined in the absence and presence of the E. coli heat
      shock protein, GroEL (chaperonin-60). At nonphysiological temperatures (15-20
      degrees C), unfolded GS spontaneously renatured to 80-90% of its original
      activity in the absence of GroEL. At near-physiological temperatures (37 degrees
      C), only 20-40% of the original activity returns. Under the latter solution
      conditions, GroEL and ATP enhance the extent of GS renaturation to 70-80% of the
      original activity at 37 degrees C. In the absence of ATP, GroEL arrests the
      renaturation of unfolded GS by forming a stable binary complex. The addition of
      ATP to this complex resulted in the release of GS subunits and formation of
      active dodecameric GS. The order of addition of ATP or unfolded GS to GroEL
      results in differences in the t1/2 values where half-maximal GS activity is
      attained. At a constant GS concentration, the formation of the GroEL.GS complex
      followed by ATP addition resulted in approximately a 2-fold increase in the
      observed t1/2 value compared to that observed when GroEL was preincubated with
      ATP before the GS renaturation reaction was initiated. These differences in
      renaturation rates may be related to binding affinity differences between the ATP
      free and -bound GroEL conformer for unfolded or partially folded protein
      substrates [Badcoe, I. G., Smith, C. J., Wood, S., Halsall, D. J., Holbrook, J.
      J., Lund, P., & Clarke, A. R. (1991) Biochemistry 30, 9195-9200].(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1348960
TI  - [Beta-2 agonists and bronchial asthma: common usage, demand, substitution or
      therapeutic replacement].

PMID- 1348958
TI  - Early-life patterns of plasma gut regulatory peptide levels in calves: effects of
      the first meals.
AB  - The effects of the first meals on the release of seven gut regulatory peptides
      were studied in newborn calves fed colostrum either at serial intervals during
      the first day of life or at 28 h only. Fasted animals showed no significant
      variation of plasma peptides until the first feed, except for somatostatin, which
      peaked at 4-5 h and declined thereafter. As assessed before and 1 h after
      feeding, the first meal tended to induce rises in plasma gastrin, cholecystokinin
      and pancreatic polypeptide, while the other peptides were unaffected. Repeated
      colostrum feeds induced marked increases in plasma gastrin, cholecystokinin,
      secretin and vasoactive intestinal peptide from 10 h on. Pancreatic polypeptide
      was transiently increased from 4 to 16 h. Feeding was followed by a transitory
      reduction of plasma somatostatin and by a prolonged decrease of plasma motilin.
      We conclude that colostrum feeding potently modulates the release of several
      regulatory peptides shortly after birth in calves. These responses may be
      important for the adaptation of gut growth, secretions and motility to food
      ingestion in the neonatal period.

PMID- 1348959
TI  - Carcass composition and resistance to fasting in neonatal piglets born of sows
      immunized against somatostatin and/or receiving growth hormone-releasing factor
      injections during gestation.
AB  - Thirty-eight gestating sows were either immunized against somatostatin (SRIF)
      and/or injected with growth hormone-releasing factor (GRF). Treatment effects on
      carcass composition and resistance of newborn piglets to a 60-hour fast were
      investigated. Protein content of carcasses at birth was increased in piglets of
      sows receiving GRF or immunized against SRIF, however, when sows received both
      treatments there was a reduction in carcass protein content (p = 0.01). Other
      carcass components were unaltered by treatments, and none of the treatments
      affected metabolic or endocrine profiles of piglets at birth. Concentrations of
      GH, IGF-I (p less than 0.01), glucagon and cortisol (p less than 0.05) increased
      linearly with duration of fast, whereas glucose values decreased. Resistance to
      fasting was unaltered in piglets from any treatment thereby suggesting that
      exogenous GRF and/or SRIF immunization of sows during gestation are unlikely to
      improve survival of newborn piglets.

PMID- 1348961
TI  - [Hypokalemia and treatment with beta-2 adrenergic agonists].

PMID- 1348962
TI  - A kinetic model of CD4+ lymphocytes with the human immunodeficiency virus (HIV).
AB  - This report describes a kinetic model of in vitro cytopathology involving
      interactions of human immunodeficiency virus (HIV) with CD4+ helper T
      lymphocytes. The model uses nonlinearly coupled, ordinary differential equations
      to simulate the dynamics of infected and uninfected cells and free virions. It is
      assumed that resting cells are more readily infected than activated cells, but
      once infected, only activated cells produce more virus. Resting cells can be
      activated by some appropriate stimulus (e.g. phytohemagglutinin, soluble
      antigen). The model predicts that the initial inoculum of virus is taken up by
      resting cells and without stimulation the system comes to a steady state of two
      populations, namely infected and uninfected cells. Stimulation of this system
      produces two additional populations, namely infected and uninfected activated
      cells which, along with the previous populations, exhibit cyclic behavior of
      growth, viral expression/release, and death. Additional stimuli enhance or
      diminish the cyclic behavior depending upon their occurrence in time. These
      simulations suggest a similar dynamics in human HIV infection and may explain a
      major factor responsible for the widely varying depletion rate of (CD4+) helper T
      cells in AIDS patients.

PMID- 1348963
TI  - Esmolol infusion during nitroprusside-induced hypotension: impact on
      hemodynamics, ventricular performance, and venous admixture.
AB  - The impact of esmolol infusion on hemodynamics, ventricular performance, venous
      admixture, sympathoadrenal, and renin-angiotensin system responses during sodium
      nitroprusside (SNP)-induced hypotension was studied in 11 patients undergoing
      lymph node dissection during general anesthesia with 60% nitrous oxide and
      fentanyl. Radial arterial and thermistor-tipped pulmonary catheters were employed
      for hemodynamic monitoring. Arterial and mixed venous blood gas tensions,
      arterial plasma renin activity (PRA), and plasma catecholamine levels were
      measured. Derived hemodynamic parameters and venous admixture (Qs/Qt) data were
      obtained from standard equations. Transesophageal echocardiography (6 patients)
      was used to assess left ventricular performance using the relationship between
      end-systolic wall stress (ESWS) and velocity of circumferential shortening
      (VCFC). After surgical incision, arterial hypotension was induced with SNP alone.
      Esmolol was infused at each of the following rates in sequence: 200, 300, and 400
      micrograms/kg/min. Each esmolol infusion lasted 20 minutes and the SNP dose was
      adjusted to maintain MAP at 55 to 60 mm Hg. The mean dose of SNP required to
      induce hypotension was 5.5 micrograms/kg/min +/- 0.5 SE. Compared to
      prehypotension values, SNP induced significant increases in Qs/Qt and reductions
      in PaO2, systemic vascular resistance (SVR), and stroke volume index (SVI).
      Esmolol infusion caused dose-dependent (highest with 400 micrograms/kg/min)
      reductions in the SNP requirement, heart rate (HR), SVI, Qs/Qt, and PRA, and also
      led to significant increases in SVR and left ventricular (LV) internal diameter
      in diastole as well as systole. Furthermore, esmolol infusion was associated with
      a dose-dependent downward and leftward shift of the ESWS versus VCFC
      relationship, implying diminished contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348964
TI  - Intramuscular use of vecuronium bromide.

PMID- 1348966
TI  - Charles F. Kettering Prize. P-glycoprotein and resistance to anticancer drugs.

PMID- 1348965
TI  - Pulmonary infiltration and eosinophilia associated with sulfasalazine therapy for
      ulcerative colitis: a case report and review of literature.
AB  - We report a 52-yr-old man with ulcerative colitis who developed sulfasalazine
      induced pulmonary infiltration with eosinophilia (PIE syndrome), which resolved
      completely after withdrawal of this drug. Desensitization to sulfasalazine was
      successful, and allowed the patient to receive this drug without recurrence of
      the pulmonary toxicity. This is the first case of the sulfasalazine-induced PIE
      syndrome in Japan; a review of the world literature found no previous cases of
      successful desensitization following sulfasalazine-induced PIE syndrome.

PMID- 1348967
TI  - c-myc, c-erbB-2, and Ki-67 expression in normal breast tissue and in invasive and
      noninvasive breast carcinoma.
AB  - c-myc, c-erbB-2, and Ki-67 expression was examined by immunohistochemistry in 11
      normal breast tissues and 42 invasive and 14 noninvasive breast carcinomas. The c
      myc product was detected in all breast carcinoma specimens and in 7 of 11 normal
      breast tissues. Invasive tumors stained more frequently with the anti-myc
      monoclonal antibody than did noninvasive tumors, while the level of expression in
      normal breast tissue was much less than that in breast cancer. Membrane staining
      of the c-erbB-2 protein was demonstrated in 29% (4 of 14) of noninvasive ductal
      carcinomas and in 45% (19 of 42) of invasive breast carcinomas. None of the 11
      normal breast tissue samples was positive. The mean value of Ki-67-positive cells
      was 0.91 +/- 0.31% for normal breast tissue, 4.57 +/- 1.36% for noninvasive
      ductal carcinoma, and 12.76 +/- 2.18% for invasive breast cancer. In 42 invasive
      breast carcinomas, the expression of c-myc, c-erbB-2, and Ki-67 proliferation
      marker were compared with lymph node status, estrogen receptor status,
      progesterone receptor status, and age of patients at diagnosis. c-erbB-2
      overexpression and Ki-67 overexpression were identified as the only factors
      associated with lymph node status. We concluded that they might be additional
      prognostic factors for breast carcinoma.

PMID- 1348968
TI  - Soluble intercellular adhesion molecule 1 is released by human melanoma cells and
      is associated with tumor growth in nude mice.
AB  - We have studied the cytokine regulation of cell surface and soluble intercellular
      adhesion molecule 1 (ICAM-1) expression on the human melanoma cell line A375M.
      Unstimulated cells express ICAM-1 on their cell surface but do not secrete
      significant levels of soluble ICAM-1. Interleukin 1, interleukin 6, tumor
      necrosis factor, and gamma-interferon all increased cell surface expression of
      ICAM-1. Tumor necrosis factor, interleukin 1, and gamma-interferon also caused
      the release of soluble ICAM-1. The serum of melanoma patients has been reported
      to contain elevated levels of soluble ICAM-1; however, the source of this ICAM-1
      is unclear. The serum from nude mice bearing s.c. human melanoma tumors was found
      to contain soluble human ICAM-1. ICAM-1 levels showed a positive correlation with
      tumor weight. The release of ICAM-1 from melanoma tumors, in response to host
      derived cytokines, may have relevance to immune recognition of the tumor.

PMID- 1348969
TI  - Homeosis in the mouse induced by a null mutation in the Hox-3.1 gene.
AB  - We have replaced the Hox-3.1 coding sequence with the E. coli lacZ gene by means
      of homologous recombination in embryonic stem cells and thus produced null mutant
      mice. Homozygous mice were born alive, but most of them died within a few days.
      In the trunk region of homozygotes, several skeletal segments were transformed
      into the likeness of more anterior ones, as observed in Drosophila with loss-of
      function homeotic mutations. The most obvious transformations were the attachment
      of the 8th pair of ribs to the sternum and the appearance of a 14th pair of ribs
      on the 1st lumbar vertebra. The pattern of beta-galactosidase activity was
      identical in heterozygotes and homozygotes and reflected faithfully the Hox-3.1
      expression pattern. Thus, the mutation modified the identity, rather than the
      position, of embryonic cells that would normally express Hox-3.1.

PMID- 1348970
TI  - Structurally distinct and stage-specific adenylyl cyclase genes play different
      roles in Dictyostelium development.
AB  - We have isolated two adenylyl cyclase genes, designated ACA and ACG, from
      Dictyostelium. The proposed structure for ACA resembles that proposed for
      mammalian adenylyl cyclases: two large hydrophilic domains and two sets of six
      transmembrane spans. ACG has a novel structure, reminiscent of the membrane-bound
      guanylyl cyclases. An aca- mutant, created by gene disruption, has little
      detectable adenylyl cyclase activity and fails to aggregate, demonstrating that
      cAMP is required for cell-cell communication. cAMP is not required for motility,
      chemotaxis, growth, and cell division, which are unaffected. Constitutive
      expression in aca- cells of either ACA or ACG, which is normally expressed only
      during germination, restores aggregation and the ability to complete the
      developmental program. ACA expression restores receptor and guanine nucleotide
      regulated adenylyl cyclase activity, while activity in cells expressing ACG is
      insensitive to these regulators. Although they lack ACA, which has a transporter
      like structure, the cells expressing ACG secrete cAMP constitutively.

PMID- 1348971
TI  - Proliferating cell nuclear antigen is required for DNA excision repair.
AB  - Fractionation of extracts from human cell lines allows nucleotide excision repair
      of damaged DNA to be resolved into discrete incision and polymerization stages.
      Generation of incised intermediates depends on the XP-A protein, a polypeptide
      that recognizes sites of damaged DNA, and on the human single-stranded DNA
      binding protein HSSB. The proliferating cell nuclear antigen (PCNA) is required
      for the DNA synthesis that converts the nicked intermediates to completed repair
      events. This need for PCNA implies that repair synthesis is carried out by DNA
      polymerase delta or epsilon. The ability to visualize repair intermediates in the
      absence of PCNA facilitates dissection of the multiprotein reaction that leads to
      incision of damaged DNA in a major pathway of cellular defense against mutagens.

PMID- 1348972
TI  - New approaches to poliovirus diagnosis using laboratory techniques: memorandum
      from a WHO meeting.
AB  - Laboratory diagnosis of poliomyelitis is an important part of the WHO initiative
      for global eradication of poliomyelitis. During the last year, new methods have
      been developed for the detection of poliovirus in clinical specimens, for
      intratypic differentiation, for the analysis of poliovirus neurovirulence, and
      for the detection of poliovirus antibodies. Progress in laboratory techniques for
      detection of poliovirus antibodies and for characterization of poliovirus
      isolates has suggested several new approaches to poliovirus diagnosis using
      laboratory techniques.

PMID- 1348973
TI  - Megestrol acetate reverses multidrug resistance and interacts with P
      glycoprotein.
AB  - We evaluated the multidrug resistance (MDR)-modulating effects of progesterone
      (PRG) and an orally active, structurally related compound, megestrol acetate
      (MA), in several MDR human cell lines. At 100 microM, both steroids inhibited the
      binding of a Vinca alkaloid photoaffinity analog to P-glycoprotein (P-gp) in MDR
      human neuroblastic SH-SY5Y/VCR cells [which show greater than 1500-fold
      resistance to vincristine (VCR) in the tetrazolium dye (MTT) assay]. However, 100
      microM MA markedly enhanced the binding of [3H]-azidopine to P-gp in both SH
      SY5Y/VCR cells and the MDR human epidermoid KB-GSV2 cell line (which displays 250
      fold resistance to VCR in the MTT assay). PRG had little effect on the binding of
      [3H]-azidopine to P-gp. MA at low doses was more effective than PRG in
      sensitizing cells to VCR and enhancing their accumulation of [3H]-VCR. The highly
      resistant SH-SY5Y/VCR subline exhibited significant collateral sensitivity to
      both steroids. These data suggest that MA may be a clinically useful modulator of
      MDR.

PMID- 1348974
TI  - Intrinsic resistance to anticancer agents in the murine pancreatic adenocarcinoma
      PANC02.
AB  - PANC02 is a ductal adenocarcinoma of the pancreas that is resistant to every
      known class of clinically active antitumor agent. To study the mechanism(s)
      underlying the intrinsic drug resistance of this tumor, a mammary adenocarcinoma
      (CA-755) that also grows in C57/BL mice and is known to be drug sensitive was
      used for comparison. PANC02 resistance and CA-755 sensitivity to several
      antitumor agents and to X-ray therapy was confirmed in mice, and PANC02 also
      demonstrated relative resistance in tissue culture. Relative to Chinese hamster
      ovary (CHO) and CA-755 cells, PANC02 did not appear to show a higher rate of
      mutation to drug resistance in culture as based on the 6-thioguanine resistance
      marker. Although P-glycoprotein characteristic of the multidrug resistance (MDR)
      phenomenon could be demonstrated at the mRNA level using a sensitive RNAse
      protection assay, the level of expression found was several orders of magnitude
      lower than that observed in phenotypic MDR cell lines. Furthermore, quinidine
      failed to increase the sensitivity of PANC02 cells to Adriamycin under conditions
      that clearly potentiated the toxicity of the drug to a CHO cell line exhibiting
      classic MDR traits. The heterogeneity in the distribution of drugs was inferred
      as being significantly greater in PANC02 versus CA-755 cells in vivo as based on
      measurements of within-animal, within-tumor variance in the distribution of the
      marker compounds inulin and antipyrine. Although it may not be the only mechanism
      involved, this greater intratumor heterogeneity in drug distribution could
      theoretically play a major role in the intrinsic drug resistance of PANC02 in
      vivo.

PMID- 1348975
TI  - Ca2+ regulation of mechanical properties of striated muscle. Mechanistic studies
      using extraction and replacement of regulatory proteins.
AB  - Extraction of regulatory proteins from thick and thin filaments of vertebrate
      striated muscle has proven to be an important approach in elucidating roles of
      these proteins in regulating contraction and in probing specific mechanisms of
      activation. For some proteins, such as LC2 and C protein, extraction has been
      fundamental in demonstrating the importance of these proteins in modulating
      contraction and the kinetics of cross-bridge interaction. For other proteins,
      such as TnC and troponin, extraction has provided significant insight into the
      importance of thin-filament intermolecular cooperativity in modulating Ca2+
      sensitivity of the contractile process. A combination of extraction and
      readdition has provided a means of introducing mutated or derivatized proteins
      into fibers to accomplish a variety of experimental objectives. The use of this
      approach is likely to grow with the need to test the functional consequences of
      site-specific mutations as part of studies directed to mechanisms of regulation
      or altered regulation in heart and skeletal muscles under normal and
      pathophysiological conditions. Such studies are likely to include extraction in
      combination with other probes of function such as flash photolysis of reaction
      substrates or products within the cross-bridge interaction cycle. Although
      extraction is a powerful approach and is likely to be extended to proteins not
      discussed in this review, an essential element of experimental design in studies
      such as these is that appropriate control experiments be done to verify that
      observed effects of the extraction protocol are specifically attributable to the
      protein that is removed.

PMID- 1348976
TI  - Effects of beta-adrenergic receptor stimulation and blockade on rate-dependent
      atrioventricular nodal properties.
AB  - Recent work has shown that alterations in the dynamic atrioventricular (AV) nodal
      response to changes in heart rate can significantly modify AV nodal function. The
      present study was designed to evaluate the nature and potential importance of
      sympathetic regulation of the rate-dependent properties of the AV node. Selective
      stimulation protocols and mathematical formulations were used to independently
      quantify AV nodal recovery, facilitation, and fatigue in 12 morphine-chloralose
      anesthetized dogs. Vagal effects were prevented by bilateral vagal transection
      and intravenous atropine, and the sinus node was crushed to allow a broader range
      of pacing cycle lengths. In seven dogs with sympathetic nerves intact, beta
      adrenergic receptor blockade increased the recovery time constant (tau rec) for
      the conduction of premature test beats from 47 +/- 2 (mean +/- SEM) msec
      (control) to 62 +/- 1 msec (p less than 0.001), whereas isoproterenol decreased
      tau rec to 38 +/- 1 msec (p less than 0.001). In addition, beta-blockade
      increased the maximum amount of rate-dependent AV nodal fatigue from 7 +/- 1 msec
      (at a cycle length of 198 +/- 9 msec [control]) to 17 +/- 2 msec (p less than
      0.001). In five dogs with decentralized stellate ganglia, tau rec was decreased
      from 71 +/- 3 msec (control) to 57 +/- 4 msec and 48 +/- 2 msec (p less than
      0.001 for each) by left stellate ganglion stimulation at 5 and 10 Hz,
      respectively. Maximum fatigue was similarly reduced from 16 +/- 1 msec (control)
      to 12 +/- 2 msec (p = NS) and 8 +/- 1 msec (p less than 0.01), respectively.
      Stellate ganglion stimulation, isoproterenol, and beta-blockade did not alter AV
      nodal facilitation. A mathematical model incorporating quantitative indexes of AV
      nodal function accurately accounted for tachycardia-dependent increases in the
      atrial-His activation interval, which were enhanced by beta-adrenergic receptor
      blockade and reduced by isoproterenol. Furthermore, this model showed that beta
      adrenergic effects were increased by increasing heart rate, with the majority of
      the rate-dependent action being due to changes in the time course of AV nodal
      recovery. We conclude that beta-adrenergic receptor stimulation alters functional
      properties that govern the AV nodal response to changes in heart rate. These
      changes in functional properties alter the ability of the AV node to conduct
      impulses during tachycardia and, as such, could play a major role in the ability
      of sympathetic stimulation to promote and beta-adrenergic receptor blockade to
      prevent the occurrence of AV nodal reentrant arrhythmias.

PMID- 1348977
TI  - Excretion of urinary enzymes after extracorporeal shock-wave lithotripsy.

PMID- 1348978
TI  - Pituitary imaging using a labelled somatostatin analogue in acromegaly.
AB  - OBJECTIVE: A number of neoplasms are known to express somatostatin receptors, and
      the use of somatostatin receptor imaging in their localization has recently been
      described. We have looked at the use of an 123I-labelled Tyr3-octreotide analogue
      of somatostatin in the visualization and functional characterization of growth
      hormone-secreting pituitary adenomas. PATIENTS: Fifteen patients with
      biochemically-proven acromegaly were scanned using this agent. In eight of these
      we also assessed acute GH responses to octreotide in order to correlate these
      responses with tumour uptake characteristics. MEASURES: Planar and single-photon
      emission computerized tomographic (SPECT) images of the head were obtained using
      a gamma-camera at 10 minutes, and 4 and 24 hours, after injection of the
      radiopharmaceutical. Blood for serum GH was sampled for 12 hours after
      administration of a single dose of 100 micrograms octreotide. RESULTS: Twelve of
      the acromegalic subjects showed significant uptake of the radiopharmaceutical in
      the pituitary fossa. Of the eight patients in whom we assessed acute GH
      responses, five demonstrated a significant fall in GH in response to octreotide.
      These subjects also showed positive uptake in the pituitary on scanning. The
      three patients who had no fall in GH had no uptake on scanning. CONCLUSIONS:
      Uptake of 123I-labelled Tyr3-octreotide in the pituitary fossa appears to
      correlate closely with the presence of a therapeutic response to octreotide.

PMID- 1348979
TI  - Long-term treatment with the dopamine agonist CV 205-502 of patients with a
      clinically non-functioning, gonadotroph, or alpha-subunit secreting pituitary
      adenoma.
AB  - OBJECTIVE: We aimed to assess the effects of prolonged treatment with the
      dopamine agonist CV 205-502 on tumour volume, visual field defects, and serum
      gonadotrophin and alpha-subunit concentrations in patients with gonadotroph,
      alpha-subunit secreting, or clinically non-functioning pituitary adenomas.
      DESIGN: The patients were treated with CV 205-502 in a final daily dose of 300
      micrograms for at least 1 year. The patients were seen at 2 or 3-week intervals
      during the first 3 months of treatment, and thereafter every 1 or 2 months.
      Computerized tomography and Goldmann perimetry were performed before treatment
      and during follow-up. Blood samples were drawn before treatment and at each out
      patient visit. PATIENTS: One patient with gonadotroph, two with alpha-subunit
      secreting, and two with clinically non-functioning pituitary adenomas were
      studied. RESULTS: Computerized tomography showed tumour shrinkage in one patient.
      In two other patients an improvement of visual field defects was observed. In
      four patients, a significant decrease in serum FSH and/or alpha-subunit
      concentrations occurred within the first 3 months of treatment. In the remaining
      patient, a significant decrease of serum FSH and alpha-subunit concentrations was
      found after more than 3 months of treatment. CONCLUSIONS: In patients with
      clinically non-functioning, gonadotroph, or alpha-subunit secreting pituitary
      tumours, long-term treatment with the dopamine agonist CV 205-502 decreases serum
      FSH and/or alpha-subunit concentrations. This decreased secretory activity from
      the pituitary tumour may be accompanied by an improvement of visual field
      defects, or tumour shrinkage on computerized tomography. Therefore, treatment
      with CV 205-502 may be useful in patients with clinically non-functioning,
      gonadotroph, or alpha-subunit secreting pituitary tumours, who cannot be operated
      upon.

PMID- 1348980
TI  - Distribution and quantification of somatostatin in inflammatory disease.
AB  - To study the possible alteration of mucosal-submucosal somatostatin-containing
      cells in inflammatory bowel diseases (IBD), the total numbers of somatostatin
      containing endocrine cells (SCEC) and submucosal ganglion cells (SGC) were
      counted in Crohn's disease (CD) and ulcerative colitis (UC). Tissue specimens
      from 25 CD and 25 UC patients were fixed in Hollande's fixative immediately after
      resection and were investigated by immunohistochemical staining. A single
      specimen was collected from 25 colorectal cancer patients, the control group.
      There was a significant difference in the number of SCEC between the tissues
      taken from the proximal colon (ascending and transverse colon) and the distal
      colon (descending and sigmoid colon). The distal colon tended to contain more
      somatostatin-immunoreactive cells than did the proximal colon. In IBD, SCEC were
      decreased in number compared with the controls. This decrease was related to the
      degree of inflammation in CD; the higher the grade of inflammation, the lower the
      number of SCEC. The number of SGC was decreased in IBD: however, a significant
      decrease was noticed only in CD. The anatomic origin and the degree of
      inflammation did not affect the number of SGC. In the present study, the decrease
      of somatostatin-containing cells was noticed in both CD and UC, but there was no
      significant difference between CD and UC. Therefore, it was assumed that this
      decrease was secondary to inflammation. However, the decrease of somatostatin,
      which works as an inhibitory peptide for inflammation, might have some role in
      the pathogenesis of IBD.

PMID- 1348981
TI  - Effect of erythropoietic stress on donor hematopoietic cell expression in
      chimeric rhesus monkeys transplanted in utero.
AB  - We have previously reported the successful development of hematopoietic chimerism
      after the in utero transplantation of fetal hematopoietic stem cells (HSC) in
      rhesus monkeys (Macaca mulatta). These animals exhibit sustained engraftment
      without immunosuppression or graft-versus-host disease (GVHD). To assess the
      functional response of the donor-derived erythropoietic population, we assayed
      the relative expression of donor and recipient hematopoietic progenitors in
      chimeric monkeys before and after anemic stress. Anemia in our chimeric animals
      resulted in increased erythropoietin (EPO) production comparable to controls.
      This was accompanied by changes in erythroid progenitor profiles, again similar
      to controls. Chimeric animals demonstrated normal reticulocytosis and
      reconstituted their hematocrit after hemorrhage at the same rate as controls. The
      donor-derived erythropoietic population exhibited normal responses to recipient
      regulatory signals and did not seem to expand at the expense of other
      hematopoietic lineages. Thus the proportions of engraftment for the myeloid and
      erythroid precursors in bone marrow and for blood lymphocytes remained stable.
      Our results demonstrate that the in utero transplantation of fetal HSC results in
      stable engraftment of donor erythropoietic progenitors, which appear to be fully
      integrated within the recipient's regulatory system. The abnormalities reported
      in the postnatal transplantation setting can then be attributed to immunologic
      reactions requiring conditioning myeloablative regimens. Fetal transplantation
      bypasses all these factors.

PMID- 1348983
TI  - Synergism in cytosolic Ca2+ mobilization between bradykinin and agonists for
      pertussis toxin-sensitive G-protein-coupled receptors in NG 108-15 cells.
AB  - Bradykinin (BK) induced a transient and pertussis toxin (PT)-insensitive increase
      in cytosolic Ca2+ ([Ca2+]i) in NG 108-15 neuroblastoma x glioma hybrid cells,
      whereas leucine-enkephalin (EK), somatostatin, norepinephrine or carbachol showed
      a weak but PT-sensitive action. When any one of the latter agonists was applied
      to the cells treated with low doses of BK, however, the level of [Ca2+]i rise
      caused by the agonist was remarkably increased in a PT-sensitive manner. The
      decreasing of extracellular Ca2+ only slightly influenced the actions of these
      agonists. Thus, synergism between a BK receptor and PT-sensitive G-protein
      coupled receptors results in marked intracellular Ca2+ mobilization by the latter
      agonists.

PMID- 1348982
TI  - Heterotypic adherence between murine leukemia/lymphoma cells and marrow stromal
      cells involves a recognition mechanism with galactosyl and mannosyl
      specificities.
AB  - We have previously shown that leukemia/lymphoma (LL) cells adhere to marrow
      stromal cells (MSC), and MSC induce clonal growth of LL cells. Even though
      CD11a/18 and CD54 are important in leukocyte and endothelial cell interaction,
      the literature suggested that these adhesion proteins are not involved in
      adhesion of hematopoietic stem cells to MSC. We therefore utilized a unique ICAM
      1- murine MSC line (MLT) to evaluate the mechanisms of adherence of LL cells
      (L5178Y and L1210) to MLT. Adherence of LL cells to extracellular matrix (ECM)
      proteins was also examined. L1210 cells attached to collagen types III and IV,
      laminin, and fibronectin, but not to collagen type I. L5178Y cells did not attach
      to any of the ECM proteins tested. The adherence of both L1210 and L5178Y to MSC
      was unaffected by rat monoclonal antibodies to murine CD11a, CD11b, and CD18.
      Neoglycoprotein probes, mannosyl-bovine serum albumin (BSA) and galactosyl-BSA,
      inhibited the adherence of L5178Y and L1210 cells to MSC by 34%-63% of controls
      at concentrations of 10(-3) and 5 x 10(-3) M. In contrast, fucosyl-BSA had no
      inhibitory effect on LL cell adherence of MLT. These data suggest that 1) LL
      cells may adhere to MSC by a lectin mechanism with mannosyl and galactosyl
      specificities; and 2) other mechanisms of adherence, not yet defined, are also
      important in this system.

PMID- 1348984
TI  - [The characteristics of the effect of mediator substances on the dynamic oxygen
      tension in the gastric mucosa].
AB  - The studies on rats were carried out to determine dynamics of pO2 in the mucous
      membrane of the stomach under the effect of acetylcholine, norepinephrine,
      serotonin, histamine, prostaglandin E2 and ATP. As to the changes in pO2 the
      mediator substances were arranged as follows (from more intensive effect to less
      pronounced one): serotonin, acetylcholine, prostaglandin E2, norepinephrine,
      histamine and ATP. As to the duration of the action--PGE2 acetylcholine,
      serotonin, norepinephrine, ATP and histamine. Under the joint action of the
      mediator substances (serotonin, norepinephrine, histamine) with acetylcholine the
      effects of domination and modulation of acetylcholine effect are found.

PMID- 1348985
TI  - Macroethical responsibilities of gynecologists and obstetricians.

PMID- 1348987
TI  - Presentation and management of eclampsia.
AB  - Three hundred forty-seven cases of eclampsia were managed at the University
      College Hospital (UCH), Ibadan, Nigeria from 1977 to 1986 (9.3 per 1000
      deliveries). Thirty-one percent of seizures occurred antenatally, 46.2% during
      labor and 23.2% postnatally. Only 5% first occurred in the hospital. Seizures
      were controlled with diazepam, lytic cocktail (chlorpromazine, pethidine and
      phenergan), sodium amylobarbitone, paraldehyde and bromethol. Maternal mortality
      was 2.9%, and perinatal mortality 193 per 1000, respectively. Prevention of
      avoidable factors (absent or poor antenatal care and prolonged labor) by the
      provision of comprehensive antenatal care will reduce the incidence of eclampsia.
      Improvement in management facilities prior to transfer to referral centers, the
      use of magnesium sulfate or diazepam to control seizures and the avoidance of
      hypotonic solutions and 50% glucose during therapy will reduce morbidity and
      mortality.

PMID- 1348986
TI  - Adjunctive antibiotic treatment of women with preterm rupture of membranes or
      preterm labor.
AB  - Subclinical infection is associated with preterm rupture of the membranes (PROM)
      and preterm labor (PTL) in many cases. It was hypothesized that antibiotic
      treatment might delay delivery and/or decrease infectious morbidity in those with
      PROM or PTL. Patients from 19 to 34 weeks with PROM and no labor or PTL with
      intact membranes (but not both) were separately randomized to receive ampicillin
      versus placebo in addition to usual therapy. There were 36 women with PTL (21
      ampicillin/15 placebo) and 84 with preterm PROM (41 ampicillin/43 placebo).
      Demographically, the treatment and placebo groups were similar. Outcome variables
      analyzed included delivery delay after treatment, maternal
      chorioamnionitis/endometritis, Apgar score, neonatal infection, or respiratory
      distress, and hospital stay. There were no significant differences between the
      ampicillin and placebo groups in those with PTL or preterm PROM as it concerned
      outcome parameters. Adjunctive ampicillin used for treatment of idiopathic PTL or
      preterm PROM was not beneficial in this study.

PMID- 1348988
TI  - Anticardiolipin antibodies in eclampsia.
AB  - Twenty patients with eclampsia were studied for the presence of anticardiolipin
      antibodies by the standard microflocculation test (quantitative) used in the
      VDRL. Four out of 20 patients (20%) were positive for anticardiolipin antibodies.
      Anticardiolipin antibodies which are antiphospholipid antibodies by decreasing
      the prostacyclin production may damage the vascular endothelium and cause
      thrombosis in the vessels. Hence, the presence of anticardiolipin antibody in
      eclampsia may have association with antiphospholipid antibody syndrome described
      by Harris et al. (Lancet ii: 1211, 1983) and its central nervous system sequelae.

PMID- 1348990
TI  - Strangulation of the umbilical cord due to combined amniotic band and true knot.
AB  - A case of fetal death due to an amniotic band and an umbilical cord true knot is
      presented. To the best of our knowledge the simultaneous occurrence of true knot
      of cord and amniotic band has never been previously reported and may shed light
      on the possible time of true knot formation in this case.

PMID- 1348989
TI  - Amoxycillin/clavulanic acid (augmentin) compared with triple drug therapy for
      pelvic inflammatory disease.
AB  - Sixty Jordanian women with pelvic inflammatory disease (PID) were studied. Of
      these, 31 were given oral amoxycillin/clavulanic acid (augmentin) for a mean
      duration of 8.4 days and 29 were given a standard triple drug regimen of oral
      ampicillin, intramuscular gentamicin and metronidazole tablets/pessaries for a
      mean duration of 7.2 days. Bacterial culture (cervical and high vaginal swabs)
      was positive in every case, most often E. coli but sometimes more than one
      pathogen was isolated. No gonococci were isolated and tests for chlamydia in 16
      patients (8 in each group) were negative, suggesting a dissociation between the
      etiology of PID and sexually transmitted disease in this Jordanian study. After 3
      days of treatment, more patients in group I (augmentin) showed diminution of
      symptoms of pain and discharge (P less than or equal to 0.05) compared to group
      II. At the end of treatment, complete cure or satisfactory improvement was
      recorded in 93.1% and 92.9% of cases in the two groups, corresponding to in vitro
      bacterial efficacy of 90.4% and 96.5%, respectively. No serious side effects were
      noted in either regimen. The results of this comparative study suggest that oral
      amoxycillin/clavulanic acid (augmentin) may be a convenient alternative to the
      triple drug regimen usually administered for the treatment of pelvic inflammatory
      disease.

PMID- 1348991
TI  - Successful pregnancy in a patient with chronic myeloid leukemia following therapy
      with cytotoxic drugs.

PMID- 1348992
TI  - Cervical priming and labor induction by multiple doses of intracervical
      prostaglandin E2 gel.
AB  - One hundred seventy-two term pregnant women with medical or obstetric conditions
      requiring induction of labor were treated with intracervical administration of
      0.5 mg prostaglandin E2 in tylose gel. Multiple administrations were necessary in
      42 cases (24.4%), two administrations in 31 cases (18.0%) and three
      administrations in 11 cases (6.4%). Intracervical administration of PGE2 tylose
      gel (0.5 mg dose) is useful to prime the cervix, induce labor, and significantly
      modify Bishop score.

PMID- 1348993
TI  - Prerupture of unscarred uterus masked by an epidural analgesia.

PMID- 1348995
TI  - Operative vaginal delivery. ACOG Technical Bulletin. Number 152--February 1991.
AB  - With any operative vaginal delivery, it is important to document in the medical
      record the indications for the procedure, including the position and station of
      the vertex and specifics of technique, timing, and ease of the procedure. The use
      of cord pH and blood gas determinations may be helpful for further evaluation of
      the fetus.

PMID- 1348994
TI  - Clinical application of a gonadotropin releasing hormone analog (buserelin) in
      the treatment of uterine leiomyomas.

PMID- 1348996
TI  - Plasminogen activators and inhibitors in normal late pregnancy, postpartum and in
      the postnatal period.
AB  - Tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA) and
      plasminogen activator inhibitors (PAI) are elevated in late pregnancy with t-PA
      and u-PA remaining so at 6 weeks postnatal. PAI-2 remains at postpartum but was
      absent by 6 weeks postnatal unlike PAI activity which was absent at postpartum
      and returned to nonpregnant level at postnatal. The potential fibrinolytic
      response to stress is much reduced in pregnancy thus increasing the risk of
      thromboembolism.

PMID- 1348997
TI  - Linkage analysis of insulin-receptor gene in familial NIDDM.
AB  - Although non-insulin-dependent diabetes mellitus (NIDDM) is clearly inherited,
      the mode of inheritance and genetic etiology remain unknown. Impaired insulin
      action is an important component of NIDDM, which may precede NIDDM onset, and
      appears to be inherited. Numerous defects of the insulin-receptor gene have been
      described in syndromes of extreme insulin resistance, and this gene is a strong
      candidate for genetic predisposition to NIDDM. To test this hypothesis, we
      examined 18 white pedigrees from Utah that had two or more siblings with NIDDM.
      For each pedigree, individuals not known to be affected were tested by standard
      oral glucose tolerance test, and diagnoses of NIDDM and impaired glucose
      tolerance were made by World Health Organization criteria. Each individual was
      typed for seven restriction-fragment-length polymorphism markers at the insulin
      receptor locus, and marker phase was established by segregation. Linkage was
      examined with the LINKAGE program under six models, including autosomal dominant
      and autosomal recessive, with individuals with impaired glucose tolerance counted
      either as affected or of unknown status and with or without sporadic cases of
      diabetes. Under each model, linkage was significantly rejected. Neither
      inspection of individual pedigree log of odds scores nor formal tests of
      heterogeneity suggested a subgroup in which linkage of NIDDM and insulin-receptor
      gene was likely. In addition, sharing of insulin-receptor gene haplotypes among
      108 affected sibling pairs drawn from the pedigrees did not deviate from that
      expected by chance alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1348998
TI  - [27th Hepato-Gastroenterology Research Forum. 16th Francophone Congress of
      Hepatology and Gastroenterology. 10th National Congress of Continuing Research in
      Hepato-Gastroenterology. Paris, 28 March-1 April 1992. Abstracts].

PMID- 1348999
TI  - Management of massive upper gastrointestinal haemorrhage from multiple sites of
      peptic ulceration with somatostatin and octreotide--a report of five cases.
AB  - Surgical management of massive upper gastrointestinal bleeding after failed
      medical treatment may be hazardous because of diffuse bleeding from several
      sites, further complicated in some patients by intercurrent disease, age, or
      previous surgery. Experience with combined somatostatin and octreotide therapy in
      five such patients is described. All were treated initially with either
      intravenous somatostatin (250 micrograms/hour) or octreotide (Sandostatin) (50
      micrograms/hour) for periods ranging from three to five days, after which they
      were given subcutaneous octreotide (50 or 100 micrograms three times daily).
      Bleeding was controlled by this regimen in all cases. The patients were all
      discharged from hospital on either ranitidine (n = 4) or omeprazole (n = 1).
      Repeat endoscopy at the end of the treatment period with somatostatin and
      octreotide (n = 1) or four weeks after discharge (n = 3) showed complete healing
      of the bleeding sites. Somatostatin and octreotide may be of value in controlling
      severe upper gastrointestinal bleeding in patients in whom surgery is hazardous
      because of bleeding from several peptic lesions further complicated in some by
      intercurrent disease or age.

PMID- 1349000
TI  - Enteral nutrition in malnutrition following gastric resection and cephalic
      pancreaticoduodenectomy.
AB  - Nutritional recovery was studied during continuous enteral nutrition in 29
      patients who had developed malnutrition after gastric surgery. Patients were
      divided into three groups according to the type of surgery involved: total
      gastrectomy (n = 10), partial gastrectomy (n = 12), or cephalic
      pancreaticoduodenectomy (n = 7). The evolution of anthropometric and biological
      nutritional parameters in each group was compared with that observed in a control
      group of 10 nonoperated anorectic patients. Significant gains in body weight, arm
      muscle circumference, triceps skinfold, serum transferrin and global nutritional
      status were observed after 3 to 4 weeks of enteral nutrition in each group, while
      serum albumin, serum cholesterol, hemoglobin, and total lymphocyte count did not
      change significantly. No significant difference was observed between the groups.
      However, weight gain tended to be slower in patients with cephalic
      pancreaticoduodenectomy. This study confirms that enteral nutrition is an
      effective method of nutritional repletion after gastrectomy. Enteral nutrition
      can be used in undernourished gastrectomized patients when dietary measures alone
      have proven inadequate.

PMID- 1349001
TI  - Genetic divergence between the Wistar-Kyoto rat and the spontaneously
      hypertensive rat.
AB  - A method of restriction fragment length polymorphism (RFLP) analysis was used to
      estimate the amount of genetic divergence between the spontaneously hypertensive
      rat (SHR) strain and the Wistar-Kyoto (WKY) strain. DNA from each strain was
      digested with eight restriction endonucleases and hybridized with six single copy
      gene sequences. The number of hybridization bands in each digestion was used to
      estimate the total number of bases analyzed and RFLPs were scored as single
      mutations. Divergence was then estimated by dividing the number of mutations by
      the number of bases analyzed. In a total of 808 bases analyzed in WKY rats, a
      minimum of 13 mutations were scored in SHR, which yields a nucleotide divergence
      of 1 change per 62 bp. This is an extremely high amount of divergence given the
      known origin of these two strains and is comparable to the maximum divergence
      possible between unrelated humans.

PMID- 1349003
TI  - Prevention of variceal rebleeding.
AB  - Recurrent variceal hemorrhage occurs in 50% to 80% of cirrhotic patients who
      survive a variceal bleeding episode. The aim of preventing rebleeding is to
      improve survival by reducing the mortality associated with rebleeding; however,
      although shunt surgery is the most effective treatment to prevent recurrent
      bleeding, it does not increase survival and is associated with an increased
      incidence of chronic portosystemic encephalopathy. The distal splenorenal shunt
      is associated with a reduced incidence of encephalopathy, compared with
      nonselective shunts, but the true magnitude and longevity of this effect is still
      controversial. beta-Blockers reduce the incidence of rebleeding, but the effect
      is modest, and there is little or no effect on mortality when compared with no
      treatment. Injection sclerotherapy reduces the incidence of rebleeding and
      improves survival when a schedule of both emergency and long-term injection is
      compared with no sclerotherapy. No technical variation of injection sclerotherapy
      has been shown to be superior to another. Endoscopic variceal banding may result
      in fewer complications but the efficacy is similar to that of injection
      sclerotherapy. Trials of long-term sclerotherapy versus beta-blockers show very
      similar mortality and rebleeding rates. Addition of beta-blockade to
      sclerotherapy does not confer any advantages when compared with sclerotherapy
      alone. Improvements in pharmacologic therapy, such as the addition of isosorbide
      mononitrate to propranolol, may in the future make drug therapy the first
      treatment option to prevent rebleeding. Shunt surgery is superior to
      sclerotherapy in preventing rebleeding and has a similar mortality; however,
      liver transplantation is technically more difficult in shunted patients, but
      shunts do not adversely affect overall survival after transplantation. There are
      few data to allow optimal selection of a particular therapy or sequence of
      therapies to prevent variceal rebleeding for any individual patient. This will
      need to be studied in large trials and is a major issue in the current clinical
      management of cirrhotics who have bled from varices.

PMID- 1349002
TI  - Treatment of acute variceal bleeding.
AB  - Once the bleeding patient has been resuscitated and the diagnosis of acute
      variceal hemorrhage established by endoscopy, emergency injection sclerotherapy
      should be employed as the therapeutic option of choice. Endoscopic band ligation
      is a promising new technique that may prove to be as effective as sclerotherapy,
      with fewer complications. Pharmacologic treatment (with vasopressin and
      nitroglycerin) and balloon tamponade remain important alternative treatments,
      both as empiric temporizing therapy before sclerotherapy can be arranged and in
      the approximately 30% of patients who continue to bleed after a single
      sclerotherapy session. Continued bleeding in many of these patients can be
      controlled with a second session of sclerotherapy. If active acute bleeding
      persists after two sclerotherapy treatments, treatment should be considered a
      failure. Some of these patients may be suitable for surgical treatment with
      either staple-gun transection of the esophagus or emergency portacaval shunting.

PMID- 1349004
TI  - Prevention of initial variceal hemorrhage.
AB  - Results from prospective controlled trials do not justify the use of either
      prophylactic shunt surgery or sclerotherapy for the prevention of initial
      variceal bleeding. Use of nonselective beta-adrenergic blockers has been shown to
      reduce significantly the risk of first variceal hemorrhage, but their effect on
      survival is marginal. Because only 25% to 40% of patients with cirrhosis and
      varices experience variceal bleeding, is it justified to place all patients with
      varices on beta-blocker therapy? The answer lies in the identification of a high
      risk population (i.e., patients with large varices and endoscopic red color
      signs) and patients who can tolerate and will be compliant with therapy. The
      duration of therapy required is unknown and perhaps requires a lifetime
      commitment. Future research will involve the use of combinations of pharmacologic
      agents to reduce further portal pressure and perhaps the use of pharmacologic
      agents and sclerotherapy. The goal of a significant improvement in survival is
      yet to be obtained.

PMID- 1349005
TI  - Pharmacologic treatment of portal hypertension.
AB  - Variceal formation and rupture are dreaded complications of chronic liver disease
      and portal hypertension. The pharmacologic treatment of portal hypertension
      should be able to stop as well as to prevent variceal hemorrhage. There are two
      principal types of vasoactive drugs in the treatment of portal hypertension:
      vasoconstrictors and vasodilators. Vasoconstrictors reduce the splanchnic blood
      flow, thereby decreasing the portal blood flow and portal pressure. Vasodilators
      act by different mechanisms, including by relaxation of myofibroblasts in the
      fibrous septa and presinusoidal areas of the liver and by direct vasodilation of
      the collateral circulation. In addition, paradoxically, they could decrease
      portal flow and pressure by inducing a baroreflex-mediated mesenteric arterial
      vasoconstriction. A miscellaneous group of drugs is also available. These drugs
      reduce the blood flow and pressure in the gastroesophageal variceal system by
      mechanisms other than vasoconstriction or vasodilation. The success of these
      pharmacologic agents is limited once the varices have ruptured. The use of beta
      blockers in the prophylaxis of the first variceal bleeding has been proven of
      benefit in this respect. Future research should be aimed at elucidating the role
      that humoral and endothelial factors play in development of the hyperdynamic
      circulatory state that characterizes patients with portal hypertension. Once
      these etiologic factors have been identified and new knowledge is acquired about
      their role in the complications of chronic liver disease, the challenge will rest
      on developing novel pharmacologic therapies specifically targeting these factors.

PMID- 1349006
TI  - Intestinal brush-border-associated enzymes: co-ordinated expression in colorectal
      cancer.
AB  - The brush border of normal small-intestine epithelial cells is rich in enzymes
      that are involved in the digestive process. Such molecules can be used as markers
      to analyze cell lineages and differentiation properties of colorectal cancers.
      Monoclonal antibodies detecting dipeptidyl peptidase-IV, aminopeptidase N,
      endopeptidase F, sucrase-isomaltase, alkaline phosphatase, maltase-glucoamylase
      and lactase have been used to analyze the phenotype of colorectal cancers,
      adjacent mucosa and histologically normal distant mucosa. The avidin-biotin
      peroxidase complex method was used. Expression of dipeptidyl peptidase-IV,
      aminopeptidase N, sucrase-isomaltase and alkaline phosphatase was common in non
      neoplastic mucosa adjacent to, and distant from, the tumor; in contrast,
      endopeptidase F, maltase-glucoamylase and lactase were rarely expressed in normal
      distant mucosa and more frequently expressed in mucosa adjacent to the tumor.
      Dipeptidyl peptidase-IV, aminopeptidase N, endopeptidase F, sucrase-isomaltase
      and alkaline phosphatase were frequently expressed in colorectal cancers, whereas
      maltase-glucoamylase and lactase were rarely expressed. Two general patterns of
      antibody reactivity were observed: diffuse cytoplasmic and apical; apical
      reactivity was generally associated with more differentiated tumors. A logistic
      predictive regression model indicated that enzyme expression in colorectal
      cancers followed a coordinate pattern, but was unrelated to the location of the
      tumor, Dukes stage or differentiation grade. In conclusion, expression of brush
      border-associated enzymes occurs frequently in colorectal cancers and is
      regulated in a co-ordinated manner. These markers can be used for the phenotypic
      sub-classification of colorectal cancers.

PMID- 1349007
TI  - Chromogranin-A expression in gastric and colon cancer tissues.
AB  - We studied the expression of chromogranin A (CgA) in human gastric (n = 17) and
      colorectal (n = 18) adenocarcinomas by nucleic acid hybridization and
      immunohistochemical analyses using a specific monoclonal antibody (MAb) to human
      chromogranin A (CgA). Some corresponding adjacent non-malignant mucosal tissues
      were also examined. RESULTS: (1) Northern blotting: of 3 normal gastric mucosas
      examined, 2 (67%) had an easily detected signal for expression of CgA. Only one
      of 14 gastric carcinomas (7%) and one of 18 colorectal carcinomas (6%) had easily
      detected RNA signals. (2) Immunohistochemical staining: all non-malignant samples
      of gastric and colonic mucosa contained CgA-positive neuroendocrine (NE) cells.
      Two of 17 (12%) gastric adenocarcinomas, and 3 of 18 (17%) of colorectal
      adenocarcinomas contained CgA-positive tumor cells. Interestingly, the positive
      cases detected by immunohistochemistry included both cases detected by Northern
      blotting. Of the 5 cases detected by immunohistochemistry, 2 gastric cancers and
      1 rectal carcinoma contained many diffusely scattered positive cells, occurring
      singly or in small clusters, while 2 colorectal carcinomas contained only
      occasional single CgA-positive tumor cells. In one of the positive gastric cases,
      a well-differentiated adenocarcinoma arising in a tubular adenoma, both the
      adenomatous and the carcinomatous elements contained positively staining cells.
      Our specific assays for CgA indicate that (1) a NE cell component, either
      diffusely scattered or occasional, occurs in about 15% of gastric and colorectal
      tumors; (2) there is no correlation between the presence of NE cells and degree
      of tumor differentiation; and (3) because only a minority of the tumor cells in
      positive cases stain for CgA, immunohistochemistry is a more sensitive method
      than Northern blotting.

PMID- 1349008
TI  - Characterization of adenovirus genome type 7h: analysis of its relationship to
      other members of serotype 7.
AB  - Ad7h is a newly identified genome type associated with severe lower acute
      respiratory infections and has so far been isolated only in South America. To
      obtain a clue to its possible origin, the degree of restriction enzyme site
      homology between adenovirus genome type 7h and those representative of the three
      described genomic clusters (GC) for serotype 7 was studied by analysis of
      pairwise comigrating DNA restriction fragments (PCRF) after digestion with BamHI,
      BglI, BglII, BstEII, EcoRI, HindIII, HpaI, SalI, SmaI, XbaI, and XhoI. The most
      closely related genome types, Ad7b, Ad7d, and Ad7g, displayed 85.7, 83.8, and
      82.8% comigrating fragments, respectively. Ad7p (GC1) was clearly distant with
      only 68.6% PCRF. No remarkable close genetic relationships (%PCRF greater than
      90) were observed with any of the genome types grouped within GC3 or with Ad7g
      (the only member of GC2), so since Ad7h seems to be related to both members of
      GC2 and GC3, it could equally be considered to represent a new cluster or to end
      up grouped in either GC2 or GC3, depending on the results of further analysis.

PMID- 1349009
TI  - Multidrug transport in human autoimmune T line cells and peripheral blood
      lymphocytes.
AB  - We studied multidrug transport in human autoimmune T line cells and peripheral
      blood leukocytes, because multidrug transport is pleiotropically limiting the
      intracellular accumulation of immunosuppressive and chemotherapeutic agents. We
      observed that a subpopulation of peripheral blood leukocytes containing CD4+,
      CD8+ and Ig+ lymphocytes expressed a multidrug transport system. Lymphocytic
      multidrug transport was seen with all peripheral blood samples analyzed, but
      showed considerable variations between individuals. In further studies with human
      lymphocytic cell lines multidrug transport was seen with 18/23 human CD4+ T cell
      lines. Interestingly, expression of multidrug transport was independent of T cell
      activation. No significant transport was observed with EBV-transformed human B
      lymphocytes, rat T line cells or rat, mouse, or guinea pig leukocytes.

PMID- 1349010
TI  - American Veterinary Medical Association. Animal Welfare Forum. Chicago, Illinois,
      November 7, 1991. Animal Welfare Symposium. Seattle Washington, July 31, 1991.

PMID- 1349011
TI  - A second serogroup of Legionella erythra serologically indistinguishable from
      Legionella rubrilucens.
AB  - Twenty-two red-autofluorescent Legionella strains were identified serologically
      as either Legionella rubrilucens or L. erythra. A rRNA probe was used for
      restriction fragment length polymorphism (RFLP) analysis of the strains and the
      patterns generated were used as an additional method of identifying the strains
      to species level. In two instances strains which were identified as L.
      rubrilucens by serology appeared to belong to the species L. erythra by RFLP
      analysis. This apparent contradiction was resolved by measurements of DNA/DNA
      homology which confirmed the existence of a second serogroup of L. erythra
      serologically indistinguishable from L. rubrilucens.

PMID- 1349012
TI  - Nerve stimulation decreases malonyl-CoA in skeletal muscle.
AB  - This study was designed to determine the effect of in situ electrical stimulation
      of the sciatic nerve on malonyl-CoA, an inhibitor of carnitine palmitoyl
      transferase, in the gastrocnemius/plantaris muscle group of rats. The left
      sciatic nerve was stimulated at a frequency of 5 Hz with 100-ms trains of
      impulses (50 Hz) for 1, 3, or 5 min. At the end of stimulation, the left and
      right (nonstimulated) gastrocnemius/plantaris muscle groups were clamp-frozen and
      later analyzed for malonyl-CoA and other metabolites. No change was observed in
      the noncontracting contralateral muscles in malonyl-CoA, ATP, creatine phosphate
      (CP), or citrate. In the stimulated muscles, malonyl-CoA decreased from 1.7 +/-
      0.1 to 1.0 +/- 0.1 nmol/g (P less than 0.05), and CP decreased from 15.8 +/- 0.9
      to 12.2 +/- 1.0 mumol/g (P less than 0.05) after 3 min of stimulation. After 5
      min of stimulation, malonyl-CoA was 1.0 +/- 0.1 nmol/g and CP was 10.3 +/- 1.3
      mumol/g. When muscles were stimulated for 5 min with single impulses (5 Hz),
      malonyl-CoA was decreased from 1.8 +/- 0.3 to 1.0 +/- 0.1 nmol/g, with no change
      in CP, ATP, or adenosine 3',5'-cyclic monophosphate. Thus a decline in malonyl
      CoA can be induced by muscle contraction independently of humoral influence.

PMID- 1349013
TI  - Phosphorylation of ryanodine receptors in rat myocytes during beta-adrenergic
      stimulation.
AB  - We studied beta-adrenergic agonist-stimulated phosphorylation of the ryanodine
      receptor in rat cardiac myocytes. The ryanodine receptor solubilized from
      myocytes and immunoprecipitated by a monoclonal antibody against canine cardiac
      ryanodine receptor was phosphorylated by the catalytic subunit of cAMP-dependent
      protein kinase (PKA). Incubation of saponin-permeabilized myocytes with [gamma
      32P]ATP also induced ryanodine receptor phosphorylation, which was enhanced
      significantly in the presence of isoproterenol. This stimulating action of
      isoproterenol was suppressed by the beta-adrenergic antagonist, propranolol. On
      the other hand, exogenously added cAMP caused a much larger stimulation of
      phosphorylation of the ryanodine receptor in permeabilized myocytes. The beta
      agonist-induced phosphorylation of the ryanodine receptor was also observed in
      intact myocytes from the newborn rat heart. These results suggest that the
      ryanodine receptor is phosphorylated by PKA during beta-adrenergic stimulation of
      cardiac myocytes.

PMID- 1349014
TI  - Increased oncogenic potential of ErbB is associated with the loss of a COOH
      terminal domain serine phosphorylation site.
AB  - The erbB oncogene encodes an altered form of the epidermal growth factor (EGF)
      receptor that lacks the extracellular ligand binding domain. This oncogene is
      exclusively leukemogenic. However, an increase in oncogenic potential and a
      broadening of the tissue specificity of tumor formation occurs after retroviral
      transduction of erbB. The increased oncogenic potential correlates with
      structural alterations within the erbB gene. One common event is the deletion of
      a serine phosphorylation site located within the COOH-terminal domain. This site
      of phosphorylation has been demonstrated to be required for EGF-induced
      desensitization of signaling by the EGF receptor (Countaway, J. L., Nairn, A. C.,
      and Davis, R.J. (1992) J. Biol. Chem. 267, 1129-1140). Here we show that the
      mutation of erbB at this negative regulatory serine phosphorylation site causes
      fibroblast transformation in vitro and is associated with an increased oncogenic
      potential in vivo.

PMID- 1349015
TI  - Heterodimerization of c-erbB2 with different epidermal growth factor receptor
      mutants elicits stimulatory or inhibitory responses.
AB  - Ligand-induced dimerization of growth factor receptors is crucial for stimulation
      of their intrinsic protein tyrosine kinase activity promoting receptor
      autophosphorylation by an intermolecular mechanism. Moreover, the suppressive and
      negative dominant action of defective epidermal growth factor receptor (EGFR) was
      shown to be caused by formation of inactive heterodimers with normal EGFR leading
      to diminished biological signaling. In this report we explore the structural
      requirements and functional significance of heterodimerization between EGFR and
      HER2. HER2 (also called c-erbB-2 or neu) is a member of the EGFR family whose
      natural ligand is still unknown. We show that in response to EGF, wild type EGFR
      and various EGFR mutants were able to undergo heterodimerization with HER2.
      Addition of EGF to transfected cells co-expressing HER2 with a kinase negative
      point mutant of EGFR (K721A) stimulated heterodimer formation, tyrosine
      phosphorylation of K721A and HER2, and tyrosine phosphorylation of one of their
      known substrates, phospholipase C gamma. However, the binding of EGF to
      transfected cells co-expressing HER2 together with another EGFR mutant CD533 (a
      deletion mutant lacking most of the cytoplasmic domain of EGFR) caused
      heterodimerization and inhibition of tyrosine kinase activity. It appears
      therefore that EGF-induced heterodimerization of EGFR and HER2 can promote either
      stimulatory or inhibitory influences on kinase activity. We propose that the
      nature of receptor interactions on the cell surface can either activate or
      inhibit the initiation of growth factor-controlled cellular signaling.

PMID- 1349016
TI  - Stable expression of HB24, a diverged human homeobox gene, in T lymphocytes
      induces genes involved in T cell activation and growth.
AB  - A diverged homeobox gene, HB24, which is known to be induced following lymphocyte
      activation, was introduced into Jurkat T cells under the control of a
      constitutive promoter. Stable transfectants of HB24 were established that
      expressed high levels of HB24 mRNA and possessed an altered phenotype suggestive
      of activated T cells. A number of genes known to be induced following T cell
      activation and associated with cell growth were increased in the transfectants,
      including c-fos, c-myc, c-myb, HLA-DR, lck, NF-kappa B, interleukin-2 and
      interleukin-2 receptor alpha (IL-2R alpha). Analysis of IL-2R alpha expression by
      transient transfection of IL-2R alpha promoter constructs into the HB24
      transfectants revealed constitutive expression (about 60% of phytohemagglutinin-
      and phorbol ester-activated Jurkat cells) that was dependent on the kappa B site
      in the IL-2R alpha promoter. Furthermore, as a consequence of the increased HB24
      mRNA levels, the Jurkat HB24 transfectants proliferated more rapidly than control
      cell lines. Thus, stable expression of HB24 confers an activation phenotype on a
      human T cell line, implicating this gene as an important transcriptional factor
      during T cell activation and growth.

PMID- 1349017
TI  - Inhibition of Molt-4-endothelial adherence by synthetic peptides from the
      sequence of ICAM-1.
AB  - Previous studies have shown that inflammatory pathologies are mediated by
      lymphocyte adhesion to endothelium and subsequent transmigration through the
      endothelial monolayer. Lymphocyte-endothelial adherence is, in part, caused by
      the leukocyte integrin LFA-1 binding to ICAM-1, its ligand on endothelial cells.
      Synthetic peptides based on specific amino acid sequences of human ICAM-1 inhibit
      the adherence of a lymphocytic cell line, Molt-4, to cytokine-stimulated
      endothelial cells. A total of 26 peptides spanning the extracellular domains of
      ICAM-1 were evaluated for their inhibitory activity in two cell adhesion assays.
      Binding of fluorescently labeled Molt-4 cells to TNF-stimulated human umbilical
      vein endothelial cells was inhibited reproducibly by peptides ICAM1-20, ICAM26
      50, ICAM40-64, ICAM132-146, and ICAM345-375. Three overlapping sequences of the
      peptide ICAM40-64, KELLLPGNNRKVYELSNVQEDSQPM, were synthesized and tested as
      well, and the sequence KELLLPGNNRKV showed the greatest inhibition. The
      inhibitory activity of these peptides was confirmed using a second assay,
      inhibition of aggregation of the Epstein-Barr virus-transformed B-lymphoblast
      line JY. Polyclonal antibodies were developed in rabbits by immunization with two
      of the peptides and characterized for their ability to inhibit lymphocyte
      endothelial adherence. These studies predict potential sites for interaction of
      the integrin receptor, LFA-1, with its ligand, ICAM-1. Thus lymphocyte
      endothelial interaction, and resulting inflammation, may be partially mediated by
      the association of ICAM-1 with LFA-1 at the specific molecular locations
      identified in this study.

PMID- 1349018
TI  - Receptor-specific desensitization with purified proteins. Kinase dependence and
      receptor specificity of beta-arrestin and arrestin in the beta 2-adrenergic
      receptor and rhodopsin systems.
AB  - Homologous desensitization of beta-adrenergic receptors, as well as adaptation of
      rhodopsin, are thought to be triggered by specific phosphorylation of the
      receptor proteins. However, phosphorylation alone seems insufficient to inhibit
      receptor function, and it has been proposed that the inhibition is mediated,
      following receptor phosphorylation, by the additional proteins beta-arrestin in
      the case of beta-adrenergic receptors and arrestin in the case of rhodopsin. In
      order to test this hypothesis with isolated proteins, beta-arrestin and arrestin
      were produced by transient overexpression of their cDNAs in COS7 cells and
      purified to apparent homogeneity. Their functional effects were assessed in
      reconstituted receptor/G protein systems using either beta 2-adrenergic receptors
      with Gs or rhodopsin with Gt. Prior to the assays, beta 2-receptors and rhodopsin
      were phosphorylated by their specific kinases beta-adrenergic receptor kinase
      (beta ARK) and rhodopsin kinase, respectively. beta-Arrestin was a potent
      inhibitor of the function of beta ARK-phosphorylated beta 2-receptors. Half
      maximal inhibition occurred at a beta-arrestin:beta 2-receptor stoichiometry of
      about 1:1. More than 100-fold higher concentrations of arrestin were required to
      inhibit beta 2-receptor function. Conversely, arrestin caused half-maximal
      inhibition of the function of rhodopsin kinase-phosphorylated rhodopsin when
      present in concentrations about equal to those of rhodopsin, whereas beta
      arrestin at 100-fold higher concentrations had little inhibitory effect. The
      potency of beta-arrestin in inhibiting beta 2-receptor function was increased
      over 10-fold following phosphorylation of the receptors by beta ARK, but was not
      affected by receptor phosphorylation using protein kinase A. This suggests that
      beta-arrestin plays a role in beta ARK-mediated homologous, but not in protein
      kinase A-mediated heterologous desensitization of beta-adrenergic receptors. It
      is concluded that even though arrestin and beta-arrestin are similar proteins,
      they display marked specificity for their respective receptors and that
      phosphorylation of the receptors by the receptor-specific kinases serves to
      permit the inhibitory effects of the "arresting" proteins by allowing them to
      bind to the receptors and thereby inhibit their signaling properties.
      Furthermore, it is shown that this mechanism of receptor inhibition can be
      reproduced with isolated purified proteins.

PMID- 1349019
TI  - Photolabeling of CheR methyltransferase with S-adenosyl-L-methionine (AdoMet).
      Studies on the AdoMet binding site.
AB  - CheR methyltransferase from Salmonella typhimurium was directly photolabeled with
      S-adenosyl-L-[methyl-3H]methionine. The labeled protein was subjected to sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and then was
      detected by fluorography. The methylase-S-adenosyl-L-methionine adduct was found
      to be stable under the experimental conditions employed. Labeling was found to be
      a function of the concentration of enzyme, S-adenosyl-L-methionine (AdoMet), and
      the intensity and time of UV irradiation. The extent of labeling and protein
      methylation was found to be inhibited by S-adenosyl-L-homocysteine, S-adenosyl-L
      ethionine, and sinefungin, which are known to compete with AdoMet for the same
      binding site on the enzyme. Our earlier data showed that the enzyme has 2
      cysteine residues and that these are important for enzyme activity. Here, we show
      that sulfhydryl reagents inhibit the photolabeling of the substrate to the
      enzyme, indicating the presence of cysteine in the vicinity of the substrate
      binding site. We also found that when Cys31 was modified to Ser, no photolabeling
      of CheR was observed, whereas a modification of Cys229 to Ser had little effect
      on the ability of AdoMet to label the enzyme. This suggests that Cys31 is located
      at or near AdoMet-binding site. The labeled protein was cleaved at tryptophan
      residues, generating two major fragments, each containing 1 cysteine residue. SDS
      PAGE and fluorography of the cleaved products indicated the presence of the label
      being associated with the Cys31 fragment. Similar results were obtained when the
      labeled protein was cleaved at glutamic acid residues using V8 protease. A
      tryptic digest of the labeled protein showed two radioactive peptide peaks when
      subjected to separation on reverse phase high pressure liquid chromatography. The
      labeled peptides were further digested to free amino acids, and the labeled amino
      acid was identified as S-methylcysteine by thin layer chromatography. These
      results indicate that Cys31 may be involved with substrate binding, as well as
      with catalysis.

PMID- 1349020
TI  - Post-translational glycosylation and proteolytic processing of a lysyl oxidase
      precursor.
AB  - The synthesis and post-translational processing of a lysyl oxidase precursor
      protein predicted by the cDNA sequence of rat aorta lysyl oxidase were
      investigated. In vitro transcription of the cloned lysyl oxidase cDNA and cell
      free translation of its mRNA transcript yielded a 47-kDa protein in the absence
      and a 50-kDa glycosylated protein in the presence of pancreatic membranes, each
      of which were immunoprecipitated with antibody against the 32-kDa bovine enzyme.
      Similarly, an N-glycosylated, 50-kDa protein band was synthesized by and
      immunoprecipitated from cultured neonatal rat aorta smooth muscle cells labeled
      with [35S]methionine. Pulse-chase studies of proteins newly synthesized by these
      cells demonstrated that the glycosylated 50-kDa precursor is secreted and that it
      is processed to the 32-kDa molecular form of lysyl oxidase principally in the
      medium. The presence of an extracellular processing enzyme activity which
      converts the 50-kDa precursor to the 32-kDa species was demonstrated by
      incubating conditioned medium of neonatal rat aorta smooth muscle cell cultures
      as a source of processing activity with conditioned medium containing 35S-labeled
      precursor synthesized but not processed by a tumorigenic cell line transfected
      with a lysyl oxidase expression vector. In contrast to the 50-kDa species, the 32
      kDa protein does not appear to be N-glycosylated consistent with the loss of N
      linked oligosaccharide units during the processing to the smaller species. The
      modes of biosynthesis and secretion of lysyl oxidase are discussed in terms of
      other nonproteolytic activities required for activation of prolysyl oxidase.

PMID- 1349021
TI  - Immunolocalization of cytoplasmic dynein to lysosomes in cultured cells.
AB  - Polyclonal antisera have been raised against cytoplasmic dynein purified from
      calf brain and rat testis. These antibodies reacted most strongly with the 74 kDa
      dynein intermediate chain, but also recognized the 410 kDa heavy chain, and the
      150 and 45 kDa polypeptides previously observed to copurify with cytoplasmic
      dynein from rat tissues. Localization studies were performed by indirect
      immunofluorescence microscopy using a fibroblast cell line. Dynein-specific
      staining appeared vesicular, distributed throughout the cell, but more
      concentrated near the nucleus. Double-labeling studies using fluorescent markers
      for membranous organelles indicated a co-localization of dynein with lysosomes.
      The distribution of the dynein-positive lysosomes was disrupted by treatment of
      the cells with microtubule-active drugs, and by acidification of the cytoplasm.
      Comparison of the distribution of lysosomes with peripheral microtubules
      indicated a high degree of coincidence. These results are consistent with the
      hypothesis that cytoplasmic dynein is involved in retrograde-directed movement of
      membranous organelles. In mitotic cells, dynein staining was also apparent along
      the microtubules of the mitotic apparatus, though vesicular staining was still
      conspicuous. The presence of dynein on vesicles as well as on spindle
      microtubules indicates that dynein distribution between these compartments may be
      regulated by distinct binding proteins.

PMID- 1349022
TI  - NMR determination of the TCA cycle rate and alpha-ketoglutarate/glutamate
      exchange rate in rat brain.
AB  - A mathematical model of cerebral glucose metabolism was developed to analyze the
      isotopic labeling of carbon atoms C4 and C3 of glutamate following an intravenous
      infusion of [1-13C]glucose. The model consists of a series of coupled metabolic
      pools representing glucose, glycolytic intermediates, tricarboxylic acid (TCA)
      cycle intermediates, glutamate, aspartate, and glutamine. Based on the rate of
      13C isotopic labeling of glutamate C4 measured in a previous study, the TCA cycle
      rate in rat brain was determined to be 1.58 +/- 0.41 mumol min-1 g-1 (mean +/-
      SD, n = 5). Analysis of the difference between the rates of isotopic enrichment
      of glutamate C4 and C3 permitted the rate of exchange between alpha-ketoglutarate
      (alpha-KG) and glutamate to be assessed in vivo. In rat brain, the exchange rate
      between alpha-KG and glutamate is between 89 +/- 35 and 126 +/- 22 times faster
      than the TCA cycle rate (mean +/- SD, n = 4). The sensitivity of the calculated
      value of the TCA cycle rate to other metabolic fluxes and to concentrations of
      glycolytic and TCA cycle intermediates was tested and found to be small.

PMID- 1349023
TI  - Regional difference in the response mediated by beta 1-adrenoceptor subtype in
      bovine cerebral arteries.
AB  - Helical strips of bovine rostral cerebral arteries (anterior cerebral, middle
      cerebral, and internal carotid artery) responded to norepinephrine with
      contractions, whereas the caudal cerebral arteries (posterior communicating,
      posterior cerebral, and basilar artery) relaxed in response to the amine. After
      blockade of alpha-adrenoceptors, norepinephrine-induced rostral artery
      contractions were reversed to relaxations, which were smaller than those in the
      caudal arteries. Isoproterenol, dobutamine, and terbutaline produced greater
      relaxations in caudal than in rostral arteries, but forskolin relaxed these
      arteries to a similar magnitude. The isoproterenol-induced relaxation was not
      affected by removal of the endothelium. Maximal relaxations induced by
      terbutaline in caudal arteries were much inferior to those by isoproterenol,
      norepinephrine, and dobutamine. Relaxations caused by isoproterenol,
      norepinephrine, and terbutaline in the caudal arteries were attenuated by
      metoprolol, but not influenced by butoxamine. Relaxations mediated possibly by
      beta 1-adrenoceptor subtypes are greater in bovine caudal cerebral arteries than
      in the rostral arteries. The heterogeneity does not appear to be associated with
      the different ability of cyclic AMP to relax arterial smooth muscle but with the
      difference of beta-adrenoceptor populations and/or processes from the receptors
      to adenylate cyclase.

PMID- 1349024
TI  - In vitro and in vivo detection of somatostatin receptors in pheochromocytomas and
      paragangliomas.
AB  - Fifty-one adrenal pheochromocytomas and 14 paragangliomas were evaluated for
      somatostatin (SRIH) receptor content with in vitro autoradiography on tissue
      sections from surgically removed tumors, using iodinated 125I[Tyr]3 octreotide as
      radioligand. Thirty-seven of 51 pheochromocytomas were SRIH receptor positive
      (73%), as well as 13 of 14 paragangliomas (93%). These SRIH receptors were of
      high affinity, pharmacologically specific for SRIH and localized on the tumor
      tissue. Using in vivo imaging techniques with radiolabeled SRIH analogs,
      paragangliomas could be visualized in five patients, as well as pheochromocytomas
      in two of three patients. All tumors tested subsequently in vitro (n = 7) were
      shown to contain SRIH receptors. A majority of pheochromocytomas were also shown
      to have a high tumoral SRIH content as measured by immunohistochemical
      techniques. Detection of SRIH messenger RNA in pheochromocytomas by in situ
      hybridization indicated that the SRIH was produced in the tumors. A weak inverse
      correlation was observed between SRIH receptor status and tumoral SRIH content,
      suggesting that SRIH receptors may be down-regulated by high levels of endogenous
      SRIH in some tumors. There was no correlation between the SRIH receptor status
      and sex, age, tumor size, benign vs. malignant tumor, or urinary metanephrine
      excretion. These tumors were also analyzed for allelic losses on various
      chromosomes and showed significant loss of heterozygosity (LOH) on chromosomes
      1p, 3p, 17p, and 22q. All eight tumors with LOH on chromosome 1p were SRIH
      receptor positive (100%), whereas only 6 of 11 tumors without LOH on 1p (55%)
      were SRIH receptor positive, suggesting a correlation between LOH on 1p and SRIH
      receptor positive status. SRIH receptors thus represent a consistent
      pathobiochemical marker for most of these adrenal and extra-adrenal tumors. In
      addition, these receptors may be of potential interest for the in vivo
      localization of these tumors.

PMID- 1349025
TI  - Hyperthyroid Graves' disease without detectable thyrotropin receptor antibodies.
AB  - TSH receptor antibodies are generally held responsible for the stimulation of the
      thyroid that characterizes patients with Graves' disease. Here, we describe nine
      patients with hyperthyroidism (triiodothyronine 4.9, 3.2-6.7 nmol/L; median,
      range) who were referred for radioiodine treatment and who had increased thyroid
      radioiodine uptake values but lacked TSH receptor antibodies determined by a
      radioreceptor assay. Furthermore, when serum immunoglobulins were studied in a
      bioassay based on a rat thyroid cell line (FRTL-5), no evidence of stimulant
      activity was observed. Subsequent to radioiodine therapy, TSH receptor antibodies
      appeared in all nine patients. The antibodies competed for TSH in the
      radioreceptor assay and, of the eight patient samples studied with the bioassay,
      six stimulated cAMP production whereas another two blocked the latter. The
      results show that a small proportion of patients with active hyperthyroid Graves'
      disease, in this study 9 out of 130 cases, do not have detectable TSH receptor
      stimulatory antibodies. A local production of antibodies within the thyroid can
      be suggested, although a more likely explanation might be that the thyroid in
      Graves' disease is activated also by other mechanisms than antibody-dependent
      ones.

PMID- 1349026
TI  - Clonal analysis of human tumors with M27 beta, a highly informative polymorphic X
      chromosomal probe.
AB  - The clonality of human tumors can be studied by X inactivation/methylation
      analysis in female patients heterozygous for X-linked DNA polymorphisms. We
      present a detailed study on clonal tumor analysis with M27 beta, a highly
      informative probe detecting a polymorphic X chromosomal locus, DXS255. The
      polymorphism detected at this locus is due to variable numbers of tandem repeats.
      The rate of constitutional heterozygosity detected by M27 beta was 88%. Normal
      tissue from gastrointestinal mucosa and thyroid showed random, hence polyclonal,
      patterns. Nonrandom clonal X inactivation was detected in all 22 malignant
      neoplasms that had been shown to be clonal by other DNA markers, such as antigen
      receptor gene rearrangements or clonal loss of heterozygosity at 17p and other
      loci. 16/48 normal blood leukocyte samples (33%) showed considerably skewed X
      inactivation patterns. Comparison of blood leukocytes and normal tissue indicated
      that in a given individual, X inactivation patterns may be tissue specific. M27
      beta was used to study the clonal composition of 13 benign thyroid nodules from
      12 multinodular goiters with rapid recent growth, traditionally termed
      "adenomas." Nine of them were clonal, whereas four nodules and tissue from a case
      of Graves' goiter were not, indicating that some, but not all, such thyroid
      nodules may represent true clonal neoplasms. The M27 beta probe permits one to
      study the clonal composition by the X inactivation approach of a wide variety of
      solid tumors from most female patients. As a control, normal tissue homologous to
      the tumor type of interest is preferable to DNA from blood leukocytes, since the
      latter may show nonrandom X inactivation patterns in a fairly high proportion of
      cases. M27 beta may, therefore, be of limited use for the clonal analysis of
      neoplasms derived from hematopoietic cells.

PMID- 1349029
TI  - Sunscreens protect epidermal Langerhans cells and Thy-1+ cells but not local
      contact sensitization from the effects of ultraviolet light.
AB  - This study compares the ability of two commonly used sunscreens--octyl dimethyl
      para-aminobenzoate (Padimate O) and 2-ethylhexyl-p-methoxycinnamate (2-EHMC)--to
      protect Langerhans cells (LC), Thy-1+ dendritic epidermal cells (Thy-1+ dEC), and
      local contact sensitivity (CS) from the effects of ultraviolet (UV) light.
      Chronic exposure of mice 5 d per week for 4 weeks with an intermediate dose of
      solar-simulated sunlight from which any UVC had been filtered reduced the LC and
      Thy-1+ dEC density of murine epidermis. This irradiation procedure was designed
      to simulate closely the daily exposure of humans to sunlight. This effect on LC
      and Thy-1+ dEC occurred in both albino and pigmented mice that develop a tan
      during the irradiation procedure, indicating that a tan does not protect these
      cells from the effects of UV light. Sunscreen preparations with Padimate O and 2
      EHMC, both of which also contained benzophenone-3, as well as Padimate O or 2
      EHMC in organic solvent, inhibited UV light from depleting LC from the epidermis
      of both mouse strains. Padimate O and 2-EHMC in organic solvent were used to
      ensure that these were the active ingredients in the sunscreen preparations. In
      contrast to the effects on LC, Padimate O, but not 2-EHMC, protected Thy-1+ dEC
      from UV exposure in both mouse strains, but neither protected against the
      development of local immunosuppression using a contact sensitivity model. Thus,
      even in a mouse strain that is sensitive to UV-induced immunosuppression, local
      immunosuppression can occur in the presence of normal densities of LC and Thy-1+
      dEC.

PMID- 1349027
TI  - Intracellular signaling in the regulation of renal Na-K-ATPase. I. Role of cyclic
      AMP and phospholipase A2.
AB  - We have reported that dopamine (DA) inhibits Na-K-ATPase activity in the cortical
      collecting duct (CCD) by stimulating the DA1 receptor, and the present study was
      designed to evaluate the mechanism of this effect. Short-term exposure (15-30
      min) of microdissected rat CCD to DA, a DA1 agonist (fenoldopam), vasopressin
      (AVP), forskolin, or dibutyryl cAMP (dBcAMP), which increase cAMP content by
      different mechanisms, strongly (approximately 60%) inhibited Na-K-ATPase
      activity. 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, completely
      blocked Na-K-ATPase inhibition by DA or fenoldopam, and IP20, an inhibitor
      peptide of cAMP-dependent protein kinase A (PKA), abolished the Na:K pump effect
      of all the cAMP agonists listed above. To verify whether the mechanism of pump
      inhibition by agents that increase cell cAMP involves phospholipase A2 (PLA2), we
      used mepacrine, a PLA2 inhibitor, which also abolished Na-K-ATPase inhibition by
      DA or fenoldopam, as well as by AVP, forskolin, or dBcAMP. Arachidonic acid (10(
      7) - 10(-4) M) inhibited Na-K-ATPase activity in dose-dependent fashion.
      Corticosterone, which induces lipomodulin, a PLA2 inhibitor protein inactivated
      by PKA, equally abolished the pump effects of DA, fenoldopam, forskolin, and
      dBcAMP, suggesting that lipomodulin might act between PKA and PLA2 in cAMP
      dependent pump regulation. We conclude that dopamine inhibits Na-K-ATPase
      activity in the CCD through a DA1 receptor-mediated cAMP-PKA pathway that
      involves the stimulation of PLA2 and arachidonic acid release, possibly mediated
      by inactivation of lipomodulin. This pathway is shared by other agonists that
      increase cell cAMP and thus stimulate PKA activity.

PMID- 1349030
TI  - Minoxidil sulfotransferase, a marker of human keratinocyte differentiation.
AB  - The sulfation of minoxidil is catalyzed by a sulfotransferase activity in a
      number of tissues including skin. To investigate further the nature of the
      minoxidil sulfotransferase activity in epithelial tissue and to compare this
      activity to that of cholesterol sulfotransferase, which has already been shown to
      be induced during the differentiation of epithelial cells, we cultured normal
      human epidermal keratinocytes in a keratinocyte growth medium for 4 d, after
      which the media were replaced with either the same growth media or media with
      increasing Ca++ concentrations. Cholesterol sulfotransferase, minoxidil
      sulfotransferase, and transglutaminase were determined during the differentiation
      of the cells in the three media. Time-activity curves that suggested two
      different sulfotransferase activities were induced during the differentiation
      process. U-77581, a competitive inhibitor of minoxidil sulfotransferase activity,
      inhibited the sulfation of minoxidil sulfotransferase activity in the
      keratinocyte homogenates, but it did not inhibit the sulfation of cholesterol.
      These data indicate that at least two sulfotransferase activities are induced
      during the differentiation of epithelial keratinocytes and minoxidil
      sulfotransferase is an early marker of that differentiation.

PMID- 1349028
TI  - Antihypertensive and metabolic effects of concomitant administration of terazosin
      and methyclothiazide for the treatment of essential hypertension.
AB  - The efficacy and safety of once-daily 2.5- or 5.0-mg methyclothiazide (MCTZ)
      added to once-daily 5.0-mg terazosin (TRZ) versus 5.0-mg TRZ alone was evaluated
      in this double-blind, multicenter study. All patients received TRZ during a 6
      week titration period. Hypertensive patients (222) (mean blood pressure of
      159/104 mm Hg) were randomized to one of three treatment groups: TRZ alone (N =
      76); TRZ+MCTZ-2.5 mg (N = 74); and TRZ+MCTZ-5.0 mg (N = 72) for the 8-week double
      blind period. Changes in the supine and standing SBP/DBP from preTRZ period were:
      TRZ alone (-4.8/-8.1 and -2.6/-6.1 mm Hg); TRZ+MCTZ-2.5 mg (-17.3/-12.4 and 
      16.0/-11.2 mm Hg); and TRZ+MCTZ-5.0 mg (-20.6/-14.4 and -23.3/-14.6 mm Hg). Blood
      pressure changes in the combination groups were significantly greater than those
      in the TRZ alone group. However, there were no statistically significant
      differences between the TRZ+MCTZ-2.5-mg and TRZ+MCTZ-5.0-mg groups. The
      combination of TRZ and MCTZ tends to mitigate the adverse effects on serum
      glucose, uric, potassium and lipids usually associated with thiazide diuretics.
      Thus, combination treatment that begins with TRZ and adds MCTZ is effective in
      lowering blood pressure without any significant adverse metabolic effects.

PMID- 1349031
TI  - Zidovudine-interferon-alpha combination therapy in patients with advanced human
      immunodeficiency virus type 1 infection: biphasic response of p24 antigen and
      quantitative polymerase chain reaction.
AB  - In an open-label dose-ranging pilot trial, 13 homosexual men with human
      immunodeficiency virus type 1 (HIV-1) p24 antigenemia after at least 6 weeks of
      zidovudine monotherapy were continued on zidovudine and given interferon-alpha,
      1.25-7.5 x 10(6) units/m2 subcutaneously three times/week. Plasma p24 antigen
      levels demonstrated a biphasic response, falling initially in 11 patients by a
      mean of 50% (95% confidence interval, 36%-64%; P = .001) at a median of 11 weeks,
      but rising steadily thereafter (P = .001). CD4+ cell counts fell by a mean of 7.1
      cells/mm3/week (P = .01). Higher initial CD4+ counts predicted greater p24
      antigen reductions. At higher interferon doses no greater reductions in p24
      antigen occurred, but side effects were more severe and CD4+ lymphocyte counts
      fell faster. Polymerase chain reaction quantification of HIV-1 DNA in 3 patients
      showed a biphasic pattern paralleling the p24 antigen response. In sum, although
      evidence of short-term effects was found, the combination showed no evidence of
      lasting antiviral activity beyond that achieved with zidovudine alone in patients
      with advanced HIV-1 infection.

PMID- 1349032
TI  - Naturally occurring soluble CD4 in patients with human immunodeficiency virus
      infection.
AB  - To investigate its use as a marker of disease severity, serum soluble CD4 (sCD4)
      was measured by ELISA in patients with human immunodeficiency virus (HIV)
      infection. Levels of sCD4 were higher in patients than in controls (P less than
      .001) but did not increase with disease severity. sCD4 release per CD4 lymphocyte
      showed a linear increase with disease severity and performed as well as beta 2
      microglobulin, a widely used marker. To study the role of sCD4 in the
      pathogenesis of HIV infection, an ELISA to detect sCD4 complexed with
      glycoprotein 120 (gp120) HIV envelope protein was developed. Preformed sCD4-gp120
      complexes were not detectable in patient serum, but addition of recombinant gp120
      showed that circulating sCD4 is capable of binding HIV envelope proteins. This
      study indicates that the sCD4-to-CD4 lymphocyte ratio increases linearly with
      disease severity and may be a useful marker of CD4 lymphocyte damage. In
      addition, serum sCD4 can bind viral particles, which may have implications for
      the use of recombinant sCD4 as a therapy in HIV infection.

PMID- 1349033
TI  - Detection of nephropathia epidemica virus RNA in patient samples using a nested
      primer-based polymerase chain reaction.
AB  - A nested primer-based polymerase chain reaction was constructed for the detection
      of Puumala virus RNA in patient samples. Puumala virus RNA was detected in cells
      from the urinary and the respiratory tracts and in peripheral blood mononuclear
      cells of patients with nephropathia epidemica. After inoculation with
      nephropathia epidemica patient material on Vero E6 cells and propagation for nine
      passages (4 months), Puumala virus RNA was detected at every passage.
      Hybridization under high-stringency conditions revealed that the overall
      nucleotide homology between the different patient isolates and the prototype
      strain (Puumala) is high. Using cDNA from Hallnas B1 strain as a probe,
      hybridization occurred only under low-stringency conditions.

PMID- 1349034
TI  - Human breast cancer: prognostic significance of the c-erbB-2 oncoprotein compared
      with epidermal growth factor receptor, DNA ploidy, and conventional pathologic
      features.
AB  - PURPOSE: A study was undertaken to define the prognostic value of the expression
      of the c-erbB-2 oncoprotein in a series of breast cancer patients when compared
      by multivariate analysis with expression of the epidermal growth factor receptor
      (EGFR), DNA ploidy, and conventional clinicopathologic features. PATIENTS AND
      METHODS: Prognostic indicators were analyzed in 165 primary breast cancers. The c
      erbB-2 oncoprotein was recognized by the polyclonal antibody 21N using an
      immunocytochemical method. Expression of the EGFR was stated immunocytochemically
      using the monoclonal antibody EGFR1. DNA ploidy was assessed in paraffin-embedded
      sections using a standard flow-cytometric method. RESULTS: Overall, 27% of
      carcinomas had membrane 21N-staining and were classified as c-erbB-2-positive.
      Overexpression of the c-erbB-2 oncoprotein was poorly associated with EGFR
      expression and the conventional pathologic features, and it was weakly associated
      with DNA ploidy and nodal status. Univariate analysis showed that c-erbB-2
      expression, nodal status, DNA ploidy, and EGFR provided significant prognostic
      information concerning 4-year relapse-free survival (RFS) with the odds ratios
      (ORs) of not relapsing of 2.94, 2.83, 2.34, and 2.20, respectively. Regarding
      overall survival (OS) at 4 years, only nodal status and DNA ploidy had prognostic
      significance, with the ORs of not dying of 2.68 and 2.80, respectively. Applying
      multivariate analysis to RFS, 21N when adjusted for nodal status, EGFR, and DNA
      ploidy (full model) failed to retain prognostic value (P = .202), whereas nodal
      status was the most significant indicator of relapse (P = .027) followed by DNA
      ploidy (P = .056) and EGFR (P = .093). CONCLUSIONS: This study suggests that
      overexpression of the c-erbB-2 oncoprotein appears to be an important indicator
      of relapse in stage I-II breast cancer when singly evaluated. Multivariate
      analysis shows that the determination both of nodal status and DNA ploidy
      improves our ability to identify subsets of patients with different prognoses,
      and allows for a better selection of patients for systemic adjuvant treatments.

PMID- 1349035
TI  - The purine analogs--a therapeutic beauty contest.

PMID- 1349036
TI  - Low-threshold Ca2+ channels mediate induction of long-term potentiation in kitten
      visual cortex.
AB  - 1. The induction mechanism of long-term potentiation (LTP) in developing visual
      cortex was studied by recording intracellular responses from layer III-IV cells
      in slice preparations of kitten visual cortex at 30-40 days after birth. 2.
      Strong stimulation of white matter produced a late depolarizing response after an
      orthodromic action potential. This depolarizing response was abolished by
      membrane depolarization or hyperpolarization caused by current injection through
      the recording electrode. In addition, this response was reduced by bath
      application of a low concentration (100 microM) of Ni2+ without any changes in
      the rising slope of the excitatory postsynaptic potential (EPSP) or orthodromic
      action potential. This suggests that this response is mediated by low-threshold
      Ca2+ channels (LTCs). 3. The involvement of LTCs in the induction of LTP was
      tested. White matter was stimulated at 2 Hz for 15 min as a conditioning stimulus
      to induce LTP, and the resultant changes in EPSPs were tested by low-frequency
      (0.1 Hz) stimulation of white matter. Conditioning stimulation produced a large N
      methyl-D-aspartate (NMDA) receptor-mediated depolarizing response in these cells,
      which obscured the presence of the late depoliarzation. Therefore the test was
      conducted in a solution containing an NMDA antagonist 2-amino-5-phosphonovalerate
      (APV). 4. Weak conditioning stimulation, which evoked no LTC responses, never
      induced LTP; whereas strong conditioning stimulation, which evoked LTC responses,
      always induced LTP. Strong conditioning stimulation failed to induce LTP when LTC
      responses were prevented either by membrane depolarization or hyperpolarization
      or by a bath application of 100 microM Ni2+. 5. In a solution without APV, the
      application of Ni2+ also prevented the induction of LTP. 6. When cells were
      impaled by an electrode containing a Ca2+ chelator 1,2-bis-(o-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA), LTP was never induced, even though LTC
      responses were evoked by conditioning stimulation. These results indicate that
      Ca2+ influx into postsynaptic cells through LTCs induces the LTP. 7. The
      responses mediated by LTCs, which were evoked by the injection of current pulses
      into the cells, were maximum at the critical period of visual cortical
      plasticity, suggesting that LTCs in postsynaptic cells regulate the plastic
      changes in developing visual cortex.

PMID- 1349037
TI  - Kindling-induced long-lasting changes in synaptic transmission in the basolateral
      amygdala.
AB  - 1. Intracellular current-clamp recordings were obtained from neurons of the
      basolateral amygdala (BLA) in an in vitro slice preparation from control and
      kindled animals. Postsynaptic potentials, elicited by stimulation of the stria
      terminalis (ST) or lateral amygdaloid nucleus (LA), were used to investigate the
      role of excitatory and inhibitory amino acid transmission in kindling-induced
      epileptiform activity. The contributions of glutamatergic and GABAergic receptor
      subtypes were analyzed by use of the non-N-methyl-D-aspartate (non-NMDA)
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the NMDA antagonist DL-2
      amino-5-phosphonovaleric acid (APV), and the GABAA antagonist bicuculline
      methiodide (BMI). 2. The synaptic waveform evoked in control neurons consisted of
      an excitatory postsynaptic potential (EPSP), a fast inhibitory postsynaptic
      potential (f-IPSP), and a slow inhibitory postsynaptic potential (s-IPSP).
      Stimulation of the ST or LA pathways evoked a burst-firing response in BLA
      neurons contralateral from the site of stimulation of kindled animals. 3. APV (50
      microM) reduced, but CNQX (10 microM) completely blocked, the burst-firing
      response in BLA neurons from kindled animals and bicuculline-induced bursting in
      control neurons. 4. Kindling significantly increased the amplitude of both the
      slow NMDA- and the fast non-NMDA-receptor-mediated components of synaptic
      transmission (s- and f-EPSPs, respectively). Furthermore, the stimulus
      intensities required to evoke EPSPs just subthreshold for action potential
      generation were significantly lower in slices from kindled animals. 5. In kindled
      neurons no significant change was observed in the membrane input resistance and
      resting membrane potential or in the number of action potentials elicited in
      response to depolarizating current injection. 6. Kindling resulted in a pathway
      specific loss of ST- and LA-evoked feedforward GABAergic synaptic transmission
      and of spontaneous IPSPs. In the same BLA neurons, direct GABAergic inhibition
      via stimulation of the LA was not affected by kindling. 7. The enhanced
      glutamatergic transmission was not due to disinhibition, because, in the presence
      of BMI (and CNQX to prevent BMI-induced bursting), the s-EPSP amplitude was still
      greater in kindled than in control neurons. 8. These results provide evidence
      that the epileptiform activity observed in BLA neurons after kindling results
      from an increase in excitatory NMDA- and non-NMDA-receptor-mediated glutamatergic
      transmission and a decrease in inhibitory gamma-aminobutyric acid (GABA)-receptor
      mediated transmission; the enhanced excitatory transmission cannot be accounted
      for by reduced inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1349038
TI  - Presynaptic modulation by GABAB receptors of glutamatergic excitation and
      GABAergic inhibition of neostriatal neurons.
AB  - 1. The present experiments investigated the effects of gamma-amino-butyric acidB
      (GABAB) receptor stimulation on the excitatory and inhibitory responses of
      neostriatal neurons evoked by stimulation of the subcortical white matter in a
      rat neostriatal slice preparation. 2. Intracellular recordings showed that single
      impulse stimulation of the corpus callosum evoked monosynaptic, 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX)-sensitive excitatory postsynaptic potentials
      (EPSPs) that were attenuated by the GABAB receptor agonist, p-chlorophenyl-GABA
      (baclofen, 0.5-10 microM) in a concentration-dependent manner. Baclofen also
      blocked the GABAA-mediated inhibition of neostriatal cell responses, which were
      revealed by paired-impulse stimulation of the subcortical white matter. Both of
      these effects persisted in slices in which the anterior cortex was removed,
      indicating that the site of action for baclofen was intrinsic to the neostriatum.
      The GABAB antagonist 3-amino-2-hydroxy-2-(4-chlorophenyl)-propanesulfonic acid
      (saclofen, 250-500 microM) reversed the depressant actions of baclofen on both
      the excitatory and inhibitory responses of neostriatal cells. 3. Concentrations
      of baclofen as high as 100 microM, which markedly attenuated EPSP amplitude, did
      not exert direct effects on resting membrane potential, current-voltage
      relationship, input resistance, or spike threshold and thus appeared to have no
      postsynaptic effect on the population of neurons recorded. 4. These results
      indicate that, in contrast to other regions of the CNS, the depressant effects of
      baclofen on glutamate-dependent EPSPs are mediated exclusively through GABAB
      receptors located presynaptically on the terminals of glutamatergic
      afferents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349039
TI  - Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in
      man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide.
AB  - Scintigraphy with 123I-Tyr-3-octreotide has several major drawbacks as regards
      its metabolic behavior, its cumbersome preparation and the short physical half
      life of the radionuclide. The use of another radiolabeled analog of somatostatin,
      111In-DTPA-D-Phe-1-octreotide, has consequently been proposed. DTPA-D-Phe-1
      octreotide can be radiolabeled with 111In in an easy single-step procedure. DTPA
      D-Phe-1-octreotide is cleared predominantly via the kidneys. Fecal excretion of
      radioactivity amounts to only a few percent of the administered radioactivity.
      For the radiation dose to normal tissues, the most important organs are the
      kidneys, the spleen, the urinary bladder, the liver and the remainder of the
      body. The calculated effective dose equivalent is 0.08 mSv/MBq. Optimal 111In
      DTPA-D-Phe-1-octreotide scintigraphic imaging of various somatostatin receptor
      positive tumors was obtained 24 hr after injection. In the six patients studied,
      tumor localization with 123I-Tyr-3-octreotide and with 111In-DTPA-D-Phe-1
      octreotide were found to be similar. However, the normal pituitary is more
      frequently visualized with the latter radiopharmaceutical. In conclusion, 111In
      DTPA-D-Phe-1-octreotide appears to be a sensitive somatostatin receptor-positive
      tissue-seeking radiopharmaceutical with some remarkable advantages: easy
      preparation, general availability, appropriate half-life and absence of major
      interference in the upper abdominal region, because of its renal clearance.
      Therefore, 111In-DTPA-D-Phe-1-octreotide may be suitable for use in SPECT of the
      abdomen, which is important in the localization of small endocrine
      gastroenteropancreatic tumors.

PMID- 1349040
TI  - Proceedings of the 39th annual meeting of the Society of Nuclear Medicine. Los
      Angeles, CA, June 9-12, 1992. Abstracts.

PMID- 1349041
TI  - Effects of beta-adrenergic blockade in an osteoblast-like cell line.
AB  - The beta-adrenergic blocking agent propranolol was shown in previous studies to
      increase orthotopic bone formation in rats. To understand the cellular mechanisms
      underlying this observation, propranolol was tested for its effects on
      osteoblastic cells, which possess adenylate cyclase-coupled beta-adrenergic
      receptors. The ability of propranolol to modulate parathyroid hormone (PTH) and
      isoproterenol effects on adenylate cyclase activity and on alkaline phosphatase
      expression was studied in the osteoblast-like rat osteosarcoma cell line ROS
      17/2.8. At concentrations between 0.1 and 10 microM, DL-propranolol specifically
      inhibited adenylate cyclase stimulation by the beta-adrenergic agonist
      isoproterenol, but did not alter either basal or PTH-stimulated activity. At
      these concentrations, propranolol also blunted the inhibition of alkaline
      phosphatase activity by isoproterenol but not PTH. Propranolol alone had minimal
      effects on ROS alkaline phosphatase activity at low concentrations (0.1-1
      microM), but became inhibitory at high concentrations (10-100 microM). Thus, the
      direct effects of physiologically relevant propranolol concentrations on
      osteoblastic cells can be attributed principally to beta-adrenergic blockade.
      These findings further suggest that propranolol may enhance bone formation by
      preserving osteoblastic activity in the face of inhibition by beta-adrenergic
      agonists.

PMID- 1349042
TI  - Effect of additives on the crystallization of glutamate dehydrogenase from
      Clostridium symbiosum. Evidence for a ligand-induced conformational change.
AB  - A new crystal form of the hexameric NAD(+)-linked glutamate dehydrogenase (GDH)
      from Clostridium symbiosum has been grown using the hanging drop method of vapour
      diffusion. The crystals are obtained either by using high concentrations of the
      amino acid substrate of the enzyme, glutamate, as the precipitant or by co
      crystallization from ammonium sulphate in the presence of either p
      chloromercuribenzene sulphonate or potassium tetracyanoplatinate. The crystals
      diffract well and X-ray photographs have established that they are in the space
      group R32. Considerations of the values of Vm indicate that the asymmetric unit
      of the R32 crystals contains a single subunit. Packing considerations based on
      the structure of the native enzyme determined from a different crystal form
      suggest that the molecule must undergo a significant conformational change in
      order to be accommodated in the new cell. Such a conformational rearrangement may
      represent an important step in the catalytic cycle.

PMID- 1349043
TI  - Agreement to develop Taxotere expected in April.

PMID- 1349044
TI  - Various methods of analysis of mdr-1/P-glycoprotein in human colon cancer cell
      lines.
AB  - BACKGROUND: Multidrug resistance (MDR) mediated by high levels of mdr-1 (also
      known as PGY1)/P-glycoprotein (Pgp) has been studied in tissue culture systems;
      however, most tumor samples which express mdr-1/Pgp have much lower levels.
      PURPOSE: We wanted to determine if levels seen clinically could be detected by
      commonly used methods and to determine if these levels conferred MDR reversible
      by Pgp antagonists. METHODS: We studied multi-drug-resistant cell lines and
      sublines with levels of mdr-1/Pgp expression comparable to those seen clinically.
      We evaluated the expression of mdr-1 RNA by Northern blot analysis, slot blot
      analysis, polymerase chain reaction (PCR) analysis, and in situ hybridization. We
      evaluated protein expression by immunofluorescence, immunohistochemistry,
      fluorescence-activated cell sorting, and immunoblotting analyses. Drug resistance
      and reversibility were determined by cell growth during continuous drug exposure.
      RESULTS: In most cases, the low level of mdr-1/Pgp present in these cell lines
      could be detected by each method, but the assays were at the limit of sensitivity
      for all methods except the PCR method. These low levels of mdr-1/Pgp are capable
      of conferring MDR, which can be antagonized by verapamil. CONCLUSIONS: Levels of
      mdr-1/Pgp similar to those found in clinical samples can be detected by each of
      these methods, but the PCR method was the most sensitive and most reliably
      quantitative. IMPLICATIONS: In vitro sensitization by the addition of verapamil
      in cell lines with these low levels of mdr-1/Pgp suggests that clinically
      detected levels may confer drug resistance in vivo.

PMID- 1349045
TI  - Laparoscopic orchiectomy and contralateral vasectomy in a patient with an
      abdominal testicle: a case report.
AB  - We present a case of a 38-year-old man with a unilateral intra-abdominal testicle
      and undesired fertility in whom orchiectomy and contralateral vasectomy were
      performed laparoscopically. Urologists have been using diagnostic laparoscopy in
      patients with nonpalpable testes to plan the definitive procedure when the
      testicle is present, and to avoid laparotomy in cases of testicular absence. This
      case of laparoscopic orchiectomy and vasectomy demonstrates that operative
      laparoscopy allows another subset of patients with cryptorchidism to avoid open
      laparotomy.

PMID- 1349046
TI  - [Immunohistological study on the expression of proliferating cell nuclear antigen
      (PCNA/cyclin) in human colorectal lesions].
AB  - The purpose of this study was to clarify the significance of immunohistological
      staining for PCNA/cyclin in human colorectal lesions. Our results: The PCNA
      positive cells existed at the bottom of colonic tubuli in the normal and
      hyperplastic conditions. In the neoplastic lesions, however, the positive cells
      were existed at the relatively surface of the mucosa (chi 2: P less than 0.01)
      and distributed irregularly from the bottom to the top of carcinoma tissue. These
      results suggested that immunohistological staining for PCNA would specifically
      detect the cell proliferation and be beneficial for practical use and clinical
      application of the diagnosis of the colorectal lesions.

PMID- 1349047
TI  - The recirculation of lymphocytes from blood to lymph: physiological
      considerations and molecular mechanisms.

PMID- 1349048
TI  - [Diagnosis of dominant renal polycystosis in adults by analysis of DNA
      polymorphism].
AB  - BACKGROUND: Adult renal polycystosis (ARP) is a dominant autosomic disease. The
      gene responsible for this disease in most families has been located on the short
      arm of chromosome 16 (16 p) by restriction analysis of the DNA polymorphisms
      (RFLP). METHODS: The existence of several polymorphic markers flanking this gene
      permits the diagnosis of any member of an affected family. A series of proximal
      and distal genetic markers have been used to study the segregation of the disease
      in a group of families with more than one affected member. RESULTS: The clinical
      and genetic results obtained from a study of 10 Spanish families with ARP have
      been reported. A high percentage of the members under 30 years of age (40%) did
      not present renal cysts. CONCLUSIONS: Restriction analysis of DNA are
      fundamentally for a disease in which a high percentage of carriers remain
      asymptomatic within the reproductive age.

PMID- 1349049
TI  - Randomised controlled trial of effect of fish-oil supplementation on pregnancy
      duration.
AB  - The high birthweights and long duration of pregnancy in the Faroe Islands led us
      to suggest that a high intake of marine-fat-derived n-3 fatty acids might prolong
      pregnancy by shifting the balance of production of prostaglandins involved in
      parturition. We have compared the effects on pregnancy duration, birthweight, and
      birth length of a fish-oil supplement, a control olive-oil supplement, and no
      supplementation. 533 healthy Danish women in week 30 of pregnancy were randomly
      assigned in a ratio of 2/1/1 to fish oil (four 1 g Pikasol capsules [containing
      2.7 g n-3 fatty acids] per day), olive oil (four 1 g capsules per day), or no
      supplement. The three groups differed in mean length of gestation (p = 0.006),
      which was highest in the fish-oil group and lowest in the olive-oil group; the
      result was similar when the analysis was restricted to women with an estimate of
      gestation length based on early ultrasound findings (443 women). Pregnancies in
      the fish-oil group were on average 4.0 (95% confidence interval 1.5-6.4) days
      longer than those in the olive-oil group; the difference in birthweight was 107
      (1-214) g. The effect of supplementation on length of gestation was influenced by
      intake of fish and of fish oil: the difference between fish-oil and other groups
      was increased by a low fish intake at baseline. Fish-oil supplementation in the
      third trimester seems to prolong pregnancy without detrimental effects on the
      growth of the fetus or on the course of labour.

PMID- 1349050
TI  - Risk factors for mother-to-child transmission of HIV-1.
AB  - Children born to women known to be infected with human immunodeficiency virus
      type 1 (HIV-1) before delivery were followed prospectively from birth in nineteen
      European centres. This analysis, encompassing the period end-December, 1984, to
      beginning-August, 1991, focuses on risk factors for mother-to-child transmission
      of HIV-1 infection. Rate of vertical transmission, based on 721 children born to
      701 mothers more than 18 months before the time of analysis, was 14.4% (95% Cl
      12.0-17.1%). Transmission was associated with maternal p24-antigenaemia and a CD4
      count of less than 700/microliters. In a multivariate analysis, odds ratios of
      transmission were: 2.25 (95% Cl 0.97-5.23) in breastfed children vs never
      breastfed children; 3.80 (1.62-8.91) in children born before 34 weeks' gestation;
      and 0.56 (0.30-1.04) in children delivered by caesarean section. Transmission was
      higher with vaginal deliveries in which episiotomy, scalp electrodes, forceps, or
      vacuum extractors were used, but only in centres where these procedures were not
      routine. On the basis of these results, HIV-infected women contemplating
      pregnancy should be counselled according to their immunological findings and, if
      they have p24-antigenaemia or a low CD4 count, warned of an increased risk of
      viral transmission. Caesarean deliveries may have a protective effect, although
      it is premature to recommend routine operative delivery. The mechanism for the
      higher infection rate in children born before 34 weeks' gestation is unclear, but
      could reflect inadequate passive or active immunity at that age, combined with
      substantial transmission during labour or delivery. The balance of evidence
      suggests that mothers with established infection can transmit HIV infection
      through breastmilk, although the relative importance of this route remains to be
      defined.

PMID- 1349051
TI  - Detection of mycobacterial DNA in sarcoidosis and tuberculosis with polymerase
      chain reaction.
AB  - The cause of sarcoidosis is unknown. However, the histological similarity between
      the disorder and tuberculosis suggests that mycobacteria might contribute to the
      pathogenesis of sarcoidosis. We have used the polymerase chain reaction (PCR) to
      detect mycobacterial DNA in clinical samples from patients with sarcoidosis. 104
      patients were included in the study (62 referred for possible tuberculosis and 20
      for possible sarcoidosis, and 22 control patients who had undergone bronchoscopy
      for other reasons). Bronchoalveolar lavage samples, bronchial washings, and
      tissue specimens (1 from each patient) underwent assay by PCR as well as
      bacteriological, histological, and cytological examination. We used two PCR
      reactions: in the first the complex-specific insertion sequence IS986/IS6110 was
      used to specifically detect DNA from Mycobacterium tuberculosis complex bacteria;
      in the second, conserved sequences of the mycobacterial groEL gene were used to
      detect DNA from mycobacteria other than M tuberculosis. The PCR was more
      sensitive than culture for diagnosis of tuberculosis. However, the false-positive
      PCR rate for M tuberculosis was 9%. M tuberculosis DNA was found in half the
      sarcoidosis patients, and non-tuberculosis mycobacterial DNA in a further 20%.
      The findings that a significant proportion of the sarcoidosis patients in this
      study have mycobacteria in their lungs and that most of these mycobacteria belong
      to M tuberculosis complex suggest an aetiological role for mycobacteria in
      sarcoidosis.

PMID- 1349052
TI  - Mutant debrisoquine hydroxylation genes in Parkinson's disease.
AB  - The frequency of fifteen genotypes of CYP2D6 (debrisoquine 4-hydroxylase) in 53
      patients with Parkinson's disease was determined by the polymerase chain reaction
      (PCR) and restriction fragment length polymorphism (RFLP) analyses and compared
      with the findings in 72 healthy controls. The commonest mutant allele, CYP2D6B,
      was twice as frequent among patients as in controls, with an approximate relative
      risk ratio of 2.70 (95% confidence interval 1.14-6.41; p = 0.0063) for subjects
      homozygous or heterozygous for this allele.

PMID- 1349053
TI  - Sensitivity of serological assays to identify blood donors with hepatitis C
      viraemia.
AB  - Blood donors at high risk of hepatitis C virus (HCV) infection were tested for
      viraemia by the polymerase chain reaction (PCR). PCR results were accepted as
      positive only if reactive in 3 of 4 tests and if confirmed in an independent
      laboratory. The sera were also tested by 6 different assays to determine the
      ability of current serological assays to detect viraemic blood donors. Of 19 PCR
      positive sera, only 13 (68%) were detected by the most sensitive of the
      serological assays. If these results are confirmed, automated PCR assays may be
      required for blood-donor screening to prevent transmission of HCV.

PMID- 1349054
TI  - Variation in the quality of cardiopulmonary resuscitation.
AB  - During instruction in basic cardiopulmonary resuscitation (CPR) skills, cardiac
      massage and mouth-to-mouth ventilation are applied without interruption for no
      longer than a few minutes. The aim of this study was to see if the quality of
      technique during the first 2 min of CPR reflects the resuscitators ability to
      perform CPR over a 15 min period. Assessments were done with a resuscitation
      mannequin from which recordings of several variables were made at 2, 5, 10, and
      15 min after the start of CPR. 60 lay volunteers who had received CPR training
      were studied, and six variables that describe the quality of CPR technique were
      recorded and scored with a predefined scoring system. No deterioration in CPR
      skills was seen during 15 min. We conclude that the initial 2 min assessment
      reflects the resuscitators ability to perform CPR over a longer period.

PMID- 1349055
TI  - Lung transplantation.

PMID- 1349056
TI  - QBC malaria diagnosis.

PMID- 1349057
TI  - Bed rest and non-proteinuric hypertension in pregnancy.

PMID- 1349058
TI  - Glucocorticoid-suppressible hyperaldosteronism.

PMID- 1349059
TI  - NCEPOD strikes again.

PMID- 1349060
TI  - Cancer pain: pathophysiology and syndromes.

PMID- 1349061
TI  - Cancer pain: management.

PMID- 1349063
TI  - Cosmetic surgery for portwine stain.

PMID- 1349062
TI  - Effects of self-help post-myocardial-infarction rehabilitation on psychological
      adjustment and use of health services.
AB  - A home-based exercise programme has been found to be as useful as a hospital
      based one in improving cardiovascular fitness after an acute myocardial
      infarction. To find out whether a comprehensive home-based programme would reduce
      psychological distress, 176 patients with an acute myocardial infarction were
      randomly allocated to a self-help rehabilitation programme based on a heart
      manual or to receive standard care plus a placebo package of information and
      informal counselling. Psychological adjustment, as assessed by the Hospital
      Anxiety and Depression Scale, was better in the rehabilitation group at 1 year.
      They also had significantly less contact with their general practitioners during
      the following year and significantly fewer were readmitted to hospital in the
      first 6 months. The improvement was greatest among patients who were clinically
      anxious or depressed at discharge from hospital. The cost-effectiveness of the
      home-based programme has yet to be compared with that of a hospital-based
      programme, but the findings of this study indicate that it might be worth
      offering such a package to all patients with acute myocardial infarction.

PMID- 1349064
TI  - The oesophagus and chest pain.

PMID- 1349065
TI  - What is low blood pressure?

PMID- 1349066
TI  - The oesophagus and chest pain.

PMID- 1349067
TI  - The oesophagus and chest pain.

PMID- 1349068
TI  - The oesophagus and chest pain.

PMID- 1349069
TI  - 2,8-Dihydroxyadenine urolithiasis, an underdiagnosed disease.

PMID- 1349070
TI  - Nicotinamide and prevention of diabetes.

PMID- 1349071
TI  - DQ (rather than DR) gene marks susceptibility to narcolepsy.

PMID- 1349072
TI  - Evaluation of mumps vaccines.

PMID- 1349073
TI  - Non-echogenic nuchal oedema as a marker in trisomy 21 screening.

PMID- 1349074
TI  - Serum and faecal tumour necrosis factor-alpha as marker of intestinal
      inflammation.

PMID- 1349075
TI  - Percutaneous catheter fragmentation of massive pulmonary embolus.

PMID- 1349076
TI  - Monitoring by PET of macrophage accumulation in brain after ischaemic stroke.

PMID- 1349077
TI  - Reversed cerebral asymmetry and breast cancer.

PMID- 1349079
TI  - Reversed cerebral asymmetry and breast cancer.

PMID- 1349078
TI  - Reversed cerebral asymmetry and breast cancer.

PMID- 1349080
TI  - Symptomless carriage of Vibrio cholerae in Peru.

PMID- 1349081
TI  - Alteplase for hepatic veno-occlusive disease complicating bone-marrow
      transplantation.

PMID- 1349082
TI  - Thalidomide for systemic lupus erythematosus.

PMID- 1349083
TI  - Intercurrent disease in healthy volunteers in pharmacological research.

PMID- 1349084
TI  - Intercurrent disease in healthy volunteers in pharmacological research.

PMID- 1349085
TI  - Proof of causation and relative risk.

PMID- 1349086
TI  - Possible low-dose-aspirin-induced gastropathy.

PMID- 1349087
TI  - Subcutaneous ondansetron.

PMID- 1349088
TI  - Transmission of HCV between spouses.

PMID- 1349089
TI  - HIV false positivity after hepatitis B vaccination.

PMID- 1349090
TI  - HIV among south London heroin users in 1991.

PMID- 1349091
TI  - Cytokines and infection in cancer patients.

PMID- 1349092
TI  - Cytokines and infection in cancer patients.

PMID- 1349093
TI  - Colonic endothelin-1 immunoreactivity in active ulcerative colitis.

PMID- 1349094
TI  - Gluten-based food coatings.

PMID- 1349095
TI  - Three-dimensional fetal ultrasound.

PMID- 1349096
TI  - Misleading phenotype in kindred with familial adenomatous polyposis.

PMID- 1349097
TI  - Calcitonin and bone diseases.

PMID- 1349098
TI  - Calcitonin and bone diseases.

PMID- 1349099
TI  - Insulin sensitivity after phototherapy for seasonal affective disorder.

PMID- 1349100
TI  - Single dose treatment of fungal nail disease.

PMID- 1349101
TI  - Protection against immune haemolytic disease of newborn infants by maternal
      monocyte-reactive IgG alloantibodies (anti-HLA-DR).
AB  - The extent to which maternal anti-Rh(D) antibodies support lysis of erythrocytes
      by monocytes in the antibody-dependent cell-mediated cytotoxicity (ADCC) assay is
      closely correlated with the severity of Rh(D) haemolytic disease of the newborn
      infant (HDN). However, in some cases HDN is much milder than would be predicted
      from the ADCC value. We postulated that maternal ADCC-blocking alloantibodies
      against paternal antigens on monocytes can protect these infants against severe
      haemolysis. We studied 13 severely Rh(D)-alloimmunised mothers whose infants
      showed unexpectedly mild HDN (group I) and 14 women with similar ADCC values but
      whose infants had severe HDN (group II). 7 group-I women had monocyte-reactive
      IgG alloantibodies that inhibited lysis by paternal monocytes in the ADCC. No
      such antibodies were found in group II (p less than 0.01). In 6 of the 7 serum
      samples with monocyte-reactive antibodies, the antibodies had HLA-DR specificity.
      Our findings suggest that Rh(D)-positive children of some severely Rh(D)
      alloimmunised women may be protected from severe HDN by maternal non-HLA-class-I,
      IgG alloantibodies against paternal monocyte blood-group antigens. These
      antibodies may inhibit the mononuclear phagocyte system of the fetus.

PMID- 1349102
TI  - Clonal p53 mutation in primary cervical cancer: association with human
      papillomavirus-negative tumours.
AB  - Analyses of cancer cell lines and of anal cancers suggest an inverse correlation
      between infection with human papillomavirus (HPV) and somatic mutation of the p53
      tumour-suppressor gene. We have investigated this association in primary cervical
      tumours. Tumour-tissue samples from 28 women with primary cancer of the cervix
      were analysed for presence of HPV sequences and for somatic mutations of the p53
      gene. Southern blot analysis and the polymerase chain reaction (PCR) showed that
      25 of the tumours contained HPV sequences; 20 were HPV16 positive and 5 HPV18
      positive. 17 tumours subjected to restriction fragment length polymorphism
      analysis for the short arm of chromosome 17 showed no evidence of allelic
      deletion. Sequencing of the entire coding region of the p53 gene by asymmetric
      PCR detected heterozygous point mutations in only 3 HPV-negative tumours. By
      contrast, in 21 HPV-positive cancers the p53 sequence was wild-type throughout.
      Our data indicate that loss of wild-type p53 function is important in the
      pathology of cervical cancer and that in the absence of an HPV-encoded gene
      product that mediates loss of p53 function, somatic mutation of the gene is
      required. This pattern of p53 mutation may partly explain the apparently worse
      prognosis of HPV-negative cervical cancers.

PMID- 1349103
TI  - Erythrocyte glutathione and tumour response to chemotherapy.
AB  - There is much evidence that tumour glutathione (GSH) concentration is an
      important factor in resistance to cancer chemotherapy. Since measurement of
      tumour GSH would require an invasive procedure in every patient, we have tried to
      find out whether GSH concentrations in peripheral-blood erythrocytes are related
      to the response to chemotherapy and thus whether they reflect those in tumour
      cells. Erythrocyte GSH concentrations were measured by spectrophotometry in
      peripheral blood from 28 patients with advanced breast cancer and 40 patients
      with other tumours before and after treatment with various conventional
      chemotherapeutic regimens. The mean pretreatment GSH concentration was lower in
      patients who showed a complete or partial response to chemotherapy than in those
      with stable or progressive disease in both the breast-cancer group (8.69 [95%
      confidence interval 5.99-11.39] vs 2.32 [1.23-3.41] mumol/g haemoglobin; p less
      than 0.01) and the group with other tumours (5.94 [4.14-7.74] vs 2.83 [1.71-3.95]
      mumol/g; p less than 0.01). The correlation of erythrocyte GSH concentration with
      response rate suggests that this measurement may be helpful in prediction of
      response to therapy.

PMID- 1349104
TI  - Cardiac effects of relaxin in rats.
AB  - Relaxin is usually considered to be a hormone of pregnancy, but porcine relaxin
      has been shown to increase heart rate in rats. We investigated the cardiac
      effects of synthetic human gene-2 relaxin (hRlx-2) in vitro in isolated rat
      atria. Synthetic hRlx-2 produced concentration-dependent positive chronotropic
      effects in spontaneously beating right atria (EC50 [concentration required to
      produce 50% of the maximal response] = 0.09 [SE 0.03] nmol/l) and concentration
      dependent positive inotropic effects in electrically driven left atria (EC50 =
      0.31 [0.02] nmol/l). The potency of hRlx-2 is greater than that of endothelin,
      angiotensin II, and (-)-isoprenaline in isolated rat atria. Relaxin has powerful
      chronotropic and inotropic effects on the heart that are probably mediated
      through a direct action on relaxin receptors.

PMID- 1349105
TI  - Identical genetic locus for Baltic and Mediterranean myoclonus.
AB  - Genetic linkage analysis shows that Baltic and Mediterranean myoclonus, two forms
      of progressive myoclonus epilepsy, are closely linked to marker D21S113 on the
      long arm of chromosome 21. Baltic and Mediterranean myoclonus are most probably
      due to mutations of the same gene.

PMID- 1349106
TI  - De-novo mutation in hereditary motor and sensory neuropathy type I.
AB  - Isolated cases of hereditary motor and sensory neuropathy type I (HMSN I, Charcot
      Marie-Tooth disease type 1) have been thought to be most frequently autosomal
      recessive. We have found that a recently discovered duplication in chromosome 17,
      responsible for most cases of autosomal dominant HMSN I, is present as a de-novo
      mutation in 9 out of 10 sporadic patients. This finding has important
      implications for genetic counselling of isolated patients with HMSN I.

PMID- 1349107
TI  - Doppler ultrasound in obstetrics.

PMID- 1349108
TI  - Lymphoma classification--where now?

PMID- 1349109
TI  - Proportional assist ventilation for ventilatory support.

PMID- 1349110
TI  - Biliary sludge: more than a curiosity.

PMID- 1349111
TI  - Individual quality of life in patients undergoing hip replacement.
AB  - Quality of life (QoL) assessment is becoming increasingly important for measuring
      the impact of illnesses, diseases, and their treatment and for deciding
      priorities when allocating resources. We developed a novel method to measure QoL
      from the perspective of the individual patient. The schedule for the evaluation
      of individual quality of life (SEIQoL) was devised from the technique known as
      judgment analysis to measure patients' level of functioning in five self
      nominated facets of life and the relative weight or importance attached to these
      areas. We applied this method, together with traditional measures of health
      status, in a prospective intervention study of 20 patients undergoing unilateral
      total hip-replacement surgery with six-month follow-up by comparison with
      matched, non-patient controls. Health status was significantly improved by hip
      replacement on the McMaster health index questionnaire (p less than 0.001) and
      the arthritis impact measurement scales (p less than 0.001). Individually
      measured QoL was significantly increased after surgery when measured by SEIQoL (p
      less than 0.02). The individual nature of QoL was reflected in the variety of
      life areas nominated as important by individual patients, the differences in
      relative weights attached to these areas, and the complex nature of the changes
      that occurred postoperatively. Our data not only highlight such individuality but
      also show that SEIQoL provides a means by which this can be assessed
      scientifically.

PMID- 1349112
TI  - Randomised comparison of oral ofloxacin alone with combination of parenteral
      antibiotics in neutropenic febrile patients.
AB  - Prompt treatment with empirical antibiotics in neutropenic febrile patients
      reduces morbidity and mortality. Most patients have been treated with parenteral
      combination antibiotics, but newer antibiotics with broad-spectrum bactericidal
      activity have made monotherapy feasible. Ofloxacin, a broad-spectrum
      fluoroquinolone, has the additional advantage that bactericidal concentrations
      can be achieved with oral administration. We have compared ofloxacin as an oral
      single agent with standard parenteral combination antibiotics for the management
      of neutropenic febrile patients in a prospective, randomised trial. Patients with
      severe neutropenia (absolute neutrophil count less than or equal to 0.5 x
      10(9)/l), fever above 38 degrees C, and ability to take drugs by mouth were
      eligible for the study. After initial investigations, 60 patients were randomly
      assigned to oral ofloxacin 400 mg twice daily and 62 to parenteral combination
      antibiotic therapy (amikacin 15 mg/kg daily, plus, at various times in the trial,
      carbenicillin, cloxacillin, or piperacillin). Patients were examined 72 h and 7
      days after the start of treatment and when neutropenia resolved. 24 (40%)
      ofloxacin-treated and 26 (42%) combination-treated patients had pyrexia of
      unknown origin (PUO). In both treatment groups, the treatment success rate was
      higher for such patients than for those with clinically or microbiologically
      documented infections (92% vs 67% [p less than 0.05] for ofloxacin; 85% vs 64%
      for combination). There were no significant differences in success rates of
      ofloxacin and combination treatment for these subgroups or overall (77% vs 73%).
      Patients with neutropenia for less than 1 week had better responses to both
      treatments than patients with longer-lasting neutropenia. There were 4 (7%)
      deaths in the ofloxacin group and 6 (10%) in the combination group. Both regimens
      were well tolerated. We conclude that oral single-agent ofloxacin is as effective
      as parenteral combination antibiotic therapy in neutropenic febrile patients,
      especially those expected to have short durations of neutropenia.

PMID- 1349113
TI  - Salmonella-triggered reactive arthritis.

PMID- 1349114
TI  - Mandatory contraception.

PMID- 1349115
TI  - Low-dose interferon-alpha and HIV infection.

PMID- 1349116
TI  - Natural history of breast cancer.

PMID- 1349117
TI  - Oestrogen and progesterone receptor dissociation and family history of breast
      cancer.

PMID- 1349118
TI  - Gene therapy for cancer.

PMID- 1349119
TI  - HTLV-I and uveitis.

PMID- 1349120
TI  - Psoriasis regression in terminal AIDS.

PMID- 1349121
TI  - Staphylococcus aureus in urine and false-positive immunoassay for Chlamydia.

PMID- 1349122
TI  - Fibroblast growth factor 6 gene expression in AIDS-associated Kaposi's sarcoma.

PMID- 1349123
TI  - Acute transverse myelitis after tetanus toxoid vaccination.

PMID- 1349124
TI  - Stroke.

PMID- 1349125
TI  - Stroke.

PMID- 1349126
TI  - Clinical value of polysomnography.

PMID- 1349127
TI  - Stroke.

PMID- 1349128
TI  - Acute ischaemic stroke during ambulatory blood pressure monitoring.

PMID- 1349129
TI  - Cyclosporin leukoencephalopathy induced by intravenous lipid solution.

PMID- 1349130
TI  - Human papillomavirus (HPV) type 16 in semen of partners of women with HPV
      infection.

PMID- 1349131
TI  - Cancer risk and radon exposure.

PMID- 1349132
TI  - Statistical correction for measurement imprecision.

PMID- 1349133
TI  - Retractor design and the lingual nerve.

PMID- 1349134
TI  - High-dose meropenem in meningitis due to Pseudomonas aeruginosa.

PMID- 1349135
TI  - Retractor design and the lingual nerve.

PMID- 1349136
TI  - Pericardial effusions after bone-marrow transplantation.

PMID- 1349137
TI  - Atopy at 3 years in high-risk infants fed whey hydrolysate or conventional
      formula.

PMID- 1349138
TI  - Fever in neutropenic patients treated with GM-CSF representing enhanced host
      defence.

PMID- 1349139
TI  - Bleeding after low-molecular-weight heparin.

PMID- 1349140
TI  - Bleeding after low-molecular-weight heparin.

PMID- 1349141
TI  - Cyclosporin ointment for psoriasis and atopic dermatitis.

PMID- 1349142
TI  - Immunisation against gastric helicobacter infection in a mouse/Helicobacter felis
      model.

PMID- 1349143
TI  - Excretion urgency in chronic obstructive pulmonary disease.

PMID- 1349144
TI  - Helicobacter pylori infection with age.

PMID- 1349145
TI  - Intramuscular medroxyprogesterone acetate for sexual aggression in elderly men.

PMID- 1349146
TI  - Viral (polyomavirus) cystitis heralding cytomegalovirus infection.

PMID- 1349147
TI  - Hyperhomocysteinaemia and recurrent spontaneous abortion or abruptio placentae.

PMID- 1349148
TI  - Decline of endogenous alpha-interferon with zidovudine.

PMID- 1349149
TI  - Gastric intramucosal pH monitoring.

PMID- 1349150
TI  - Effect of the anticonvulsant U-54494A on cortical neuron excitability: comparison
      to the kappa agonist U-50488H.
AB  - U-54494A, a 1,2-diamine anticonvulsant, and U-50488H, a structurally related
      agonist for opiate kappa receptors, were tested for effects on spontaneous and
      glutamate-evoked firing rates in cerebral cortex of urethane-anesthetized male
      Sprague-Dawley rats. Iontophoretic application of 1,2-diamines, glutamate diethyl
      ether (GDEE), or procaine depressed spontaneous and amino acid-induced firing of
      cortical neurones. With continued ejection of 1,2-diamines or procaine, firing
      was silenced completely, but GDEE could maintain a partial suppression. A rapid
      rebound of excitation followed cessation of procaine ejections, but not of other
      agents. Procaine, but not U-54494A, blocked axonal conduction of rabbit sciatic
      nerve. Intravenous U-54494A and U-50488H significantly depressed spontaneous
      firing rates of cortical neurones, but only the U-50488H effects were antagonized
      by naloxone. It is concluded that U-54494A inhibits neuronal excitability by a
      mechanism independent of the analgesic kappa receptor. Biochemical and
      physiological studies have demonstrated that U-54494A and the kappa opioid
      agonist U-50488H (a structurally related diamine) (1) have anticonvulsant
      activity (2, 3). U-54494A lacks kappa analgesic and sedative properties, and it
      has been suggested that the mechanism of action of this compound may be mediated
      by a subtype of kappa opioid receptor (3). The effects of kappa analgesics on
      neuronal firing in nociceptive pathways have been described (4, 5). However, no
      previous electrophysiological studies on U-54494A have been done. Since U-54494A
      antagonizes amino acid-induced seizures (3), the interactions of this compound
      with glutamate are of interest. In the present study, the antagonist efficacies
      of U-54494A and U-50488H for inhibiting spontaneous and 1-glutamate stimulated
      neurons of the rat prefrontal cerebral cortex were assessed after i.v. and
      microiontophoretic administration of the compounds. Effects observed with these
      routes of administration allow the observation of neuronal changes occurring
      immediately after administration and take advantage of the high temporal
      resolution provided by the electrophysiological recording techniques of single
      cells. A preliminary account of portions of this work have been previously
      disclosed (6).

PMID- 1349151
TI  - AIDS--an autoimmune model.
AB  - In AIDS a complementary interface between the HIV virus and the CD4 molecule of
      the T4 lymphocyte suggest a possible cause of immune self-recognition. Because of
      this complementarity, an anti-idiotypic immune response to the CD4 attachment
      area of HIV should result in an autoimmune reaction to CD4 positive lymphocytes.
      Experimental demonstration of such an immune recognition model by autoreactive
      lymphocytes is presented and a hypothetical immune response unit is suggested.

PMID- 1349152
TI  - [Biological aspects of the development of drug dependence].

PMID- 1349153
TI  - Preferential desensitization of beta- versus alpha 2-adrenergic receptors
      accelerates loss of response to norepinephrine in primary glial cultures.
AB  - The effect of norepinephrine (NE) on cAMP accumulation in primary glial cultures
      is mediated by two functionally opposing receptor subtypes. beta-Adrenergic
      receptor activation increases cAMP formation, whereas simultaneous alpha 2
      adrenergic receptor activation partially inhibits this effect. We compared
      desensitization of these two responses during exposure to selective agonists or
      NE. Pretreatment with the beta-selective agonist isoproterenol (ISO) decreased
      responses to ISO, ISO plus the alpha 2-selective agonist UK 14,304 (UK), and NE.
      However, ISO plus UK and NE responses decreased more, relative to their control
      values, than did responses to ISO alone. Pretreatment with UK increased cAMP
      responses to both ISO and forskolin (sensitization), with little effect on alpha
      2-mediated inhibition of these responses. Pretreatment with NE caused effects
      similar to those of both ISO and UK pretreatment. NE pretreatment decreased
      responses to ISO, ISO plus UK, and NE, sensitized responses to forskolin, and had
      little effect on alpha 2-mediated inhibition. Thus, chronic agonist exposure
      desensitizes beta-adrenergic receptors more rapidly and at much lower
      concentrations than alpha 2-adrenergic receptors in these cultures. The
      continuing alpha 2 inhibition during diminishing beta stimulation functionally
      accelerates the loss of the NE response.

PMID- 1349154
TI  - Identification of a single amino acid residue responsible for the binding of a
      class of beta-adrenergic receptor antagonists to 5-hydroxytryptamine1A receptors.
AB  - The 5-hydroxytryptamine1A (5-HT1A) receptor can bind certain beta-adrenergic
      receptor antagonists, such as pindolol, with high affinity. Such pharmacological
      cross-reactivity suggests a structural similarity in the ligand binding site
      between the two receptors. To identify this structural entity, we mutated Asn385
      in the seventh transmembrane domain of the human 5-HT1A receptor, based on the
      observation that this residue is conserved in all 5-HT1A and beta-adrenergic
      receptors of different species but is absent in all other cloned guanine
      nucleotide-binding protein-coupled receptors. This single point mutation (Asn385
      to valine) causes a highly selective decrease in the affinity of pindolol and
      other aryloxyalkylamines for the mutant receptor (about 100-fold), while
      producing only minor changes in the binding of other 5-HT agonists and
      antagonists. The results provide direct evidence that Asn385 is responsible for
      the high affinity interaction between 5-HT1A receptors and aryloxyalkylamine beta
      adrenergic antagonists but is not required for the binding of other chemical
      classes of ligands.

PMID- 1349155
TI  - L-proline activates glutamate and glycine receptors in cultured rat dorsal horn
      neurons.
AB  - The pharmacological actions of L-proline on excitatory and inhibitory amino acid
      receptors have been characterized under voltage-clamp conditions, using cultured
      dissociated neurons from the dorsal horn of the rat spinal cord. At a holding
      potential of -62 mV, millimolar concentrations of L-proline elicited an inward
      current that was partially antagonized by D-(-)-2-amino-5-phosphonopentanoic acid
      (APV), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and strychnine and was
      virtually abolished (97% block) by a combination of all three antagonists.
      Currents evoked by D-proline were abolished by strychnine alone. APV-, CNQX-, and
      strychnine-sensitive components of L-proline-evoked currents were isolated using
      various combinations of the three antagonists. These currents were identical to
      currents elicited by N-methyl-D-aspartate (NMDA), kainate, and glycine,
      respectively, with respect to antagonist specificity, reversal potential, and
      ionic permeability. The APV- and strychnine-sensitive currents also showed a time
      dependence similar to that of the currents elicited by NMDA and glycine. EC50
      values could not be calculated, because the response did not saturate within the
      tested range of L-proline concentrations (0.3-50 mM). Estimates of relative
      potency were obtained, however, by comparison with responses elicited by
      selective agonists. The APV-sensitive, CNQX-sensitive, and strychnine-sensitive
      currents evoked by 10 mM L-proline were comparable in size to currents elicited
      by 15 microM NMDA, 5 microM kainate, and 30 microM glycine, respectively. L
      Proline was found to elicit an increase in intracellular [Ca2+] that was
      dependent upon Ca2+ entry into the cell. These Ca2+ responses were enhanced by
      strychnine and partially antagonized by APV, CNQX, or Mg2+. Our results using
      dorsal horn neurons grown in culture indicate that L-proline is a weak agonist at
      strychnine-sensitive glycine receptors and at both NMDA and non-NMDA glutamate
      receptors. These observations should help in interpreting the confusing array of
      L-proline actions that have been described using more intact nervous system
      preparations. Furthermore, the ability of L-proline to stimulate Ca2+ entry after
      activation of excitatory amino acid receptors implicates L-proline as a potential
      endogenous excitotoxin.

PMID- 1349156
TI  - Identification of separate determinants on the thyrotropin receptor reactive with
      Graves' thyroid-stimulating antibodies and with thyroid-stimulating blocking
      antibodies in idiopathic myxedema: these determinants have no homologous sequence
      on gonadotropin receptors.
AB  - Deletions, substitutions, or mutations of the rat TSH receptor extracellular
      domain between residues 20 and 107 (all residue numbers are determined by
      counting from the methionine start site) have been made by site-directed
      mutagenesis of receptor cDNA. After transfection in Cos-7 cells, constructs were
      evaluated for their ability to bind [125I]TSH or respond to TSH and thyroid
      stimulating antibodies (TSAbs) from Graves' patients in assays measuring cAMP
      levels of the transfected cells. Assay results were compared to results from Cos
      7 cells transfected with wild-type receptor constructs or vector alone. We
      identify threonine-40 as a TSAb-specific site whose mutation to asparagine, but
      not alanine, reduces TSAb activity 10-fold, but only minimally affects TSH
      increased cAMP levels. We show that thyroid-stimulating blocking antibodies
      (TSBAbs), which block TSH or TSAb activity and are found in hypothyroid patients
      with idiopathic myxedema, continue to inhibit TSH-stimulated cAMP levels when
      threonine-40 is mutated to asparagine or alanine, suggesting that TSBAbs interact
      with different TSH receptor epitopes than the TSAb autoantibodies in Graves'
      patients. This is confirmed by the demonstration that these TSBAbs interact with
      high affinity TSH-binding sites previously identified at tyrosine-385 or at
      residues 295-306 of the extracellular domain of the TSH receptor. This is
      evidenced by a loss in the ability of TSBAbs to inhibit TSAb activity when these
      residues are mutated or deleted, respectively. Since the TSAb and TSBAb epitopes
      are in regions of the extracellular domain of the TSH receptor that have no
      homology in gonadotropin receptors, these data explain at least in part the organ
      specific nature of TSH receptor autoantibodies in autoimmune thyroid disease.
      Data are additionally provided which indicate that residues 30-37 and 42-45,
      which flank the TSAb epitope at threonine-40, appear to be ligand interaction
      sites more important for high affinity TSH binding than for the ability of TSH to
      increase cAMP levels and that cysteine-41 is critical for TSH receptor
      conformation and expression on the surface of the cell. Thus, despite unchanged
      maximal values for TSH-increased cAMP levels, substitution of residues 42-45 or
      deletion of residues 30-37 results in receptors, which, by comparison to wild
      type constructs, exhibit significantly worsened Kd values for TSH binding than
      EC50 values for TSH- or TSAb-increased cAMP activity.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1349157
TI  - Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated
      protein folding.
AB  - The main stress proteins of Escherichia coli function in an ordered protein
      folding reaction. DnaK (heat-shock protein 70) recognizes the folding polypeptide
      as an extended chain and cooperates with DnaJ in stabilizing an intermediate
      conformational state lacking ordered tertiary structure. Dependent on GrpE and
      ATP hydrolysis, the protein is then transferred to GroEL (heat-shock protein 60)
      which acts catalytically in the production of the native state. This sequential
      mechanism of chaperone action may represent an important pathway for the folding
      of newly synthesized polypeptides.

PMID- 1349158
TI  - Alpha 2-adrenoceptor modulation of rat ventral hippocampal 5-hydroxytryptamine
      release in vivo.
AB  - The putative existence of a functional alpha 2-adrenoceptor-mediated modulation
      of 5-HT release in vivo from serotonergic neuronal terminals in the ventral
      hippocampus was investigated using intracerebral microdialysis in chloral hydrate
      anaesthetised rats. The alpha 2-adrenoceptor agonist clonidine (0.01-0.3 mg/kg,
      SC) dose-dependently decreased the 5-HT output. The response to clonidine was
      antagonized by systemic or local administration of the alpha 2-adrenoceptor
      antagonist idazoxan (0.1 mg/kg, SC, or 10 mumol/l, via the dialysis perfusion
      medium). Similarly, the 5-HT release-suppressing response to the thiazole alpha 2
      adrenoceptor agonist jingsongling (0.1 mg/kg, SC) was blocked by idazoxan (0.1
      mg/kg, SC). The mixed beta-adrenoceptor/5-HT1 receptor antagonist pindolol (8.0
      mg/kg, SC) did not affect the clonidine-induced reduction of 5-HT release.
      Tyrosine hydroxylase inhibition by means of alpha-methyl-para-tyrosine (alpha-MT;
      250 mg/kg, IP) caused a drastic reduction (greater than 80%) in dialysate 3,4
      dihydroxyphenyl acetic acid (DOPAC) output but did not affect the 5-HT output per
      se over 3 h post-injection. Nor did the alpha-MT pretreatment prevent, but
      instead significantly enhanced, the 5-HT release-suppressing effect of clonidine.
      The results demonstrate that the release of 5-HT from serotonergic nerve
      terminals in rat ventral hippocampus in vivo is modulated by alpha 2
      adrenoceptors, probably both by heteroreceptors on the axon terminals of the
      serotonergic neurones and by other alpha 2-adrenoceptor sites situated pre-
      and/or postsynaptic to the noradrenergic terminals. Our results also suggest that
      while functionally operative, these sites may receive little physiological tone,
      at least in chloral hydrate-anaesthetised rats.

PMID- 1349160
TI  - Evidence for verapamil-induced functional inhibition of noradrenergic
      neurotransmission in vivo.
AB  - Contractions of the cat nictitating membrane have been used to explore the
      effects of calcium channel blockers on neurotransmission in vivo, by comparing
      the effects of verapamil and nifedipine on contractions of nictitating membrane
      following either electrical stimulation of the superior cervical ganglion or
      intravenous injection of the alpha-adrenoceptor agonist phenylephrine. Verapamil
      (0.3, 0.6 and 1.2 mg/kg, iv) produced a dose related and reversible inhibition of
      stimulation induced contractions but did not affect phenylephrine responses of
      nictitating membrane. Intravenous nifedipine (10, 20 and 40 micrograms/kg)
      produced inconsistent effects on both stimulation- and phenylephrine-induced
      contractions of the nictitating membrane. Thus only verapamil appears to
      selectively affect noradrenergic neurotransmission in this model, possibly by
      altering the neurotransmitter release from the terminals innervating the
      nictitating membrane in the cat.

PMID- 1349159
TI  - The effect of intrastriatal application of directly and indirectly acting
      dopamine agonists and antagonists on the in vivo release of acetylcholine
      measured by brain microdialysis. The importance of the post-surgery interval.
AB  - The effect of intrastriatal application of D-1, D-2 and indirect dopaminergic
      drugs on the release of striatal acetylcholine as a function of the post
      implantation intervals was studied using in vivo microdialysis. The dopamine D-2
      agonists LY 171555 and (-)N0437 inhibited the release of striatal acetylcholine
      to 40% of control values 16-24 h after implantation of the dialysis cannula. When
      LY 171555 was infused 40-48 h after implantation of the dialysis cannula, the
      response was attenuated to 20% of control values. Meanwhile, the effectiveness of
      infusions of the antagonists (-)sulpiride and haloperidol was augmented from a
      non significant effect at 16-24 h to a 150% increase 40-48 h after implantation
      of the cannula. Infusions of the dopamine releasing agent amphetamine or the
      dopamine uptake inhibitor nomifensine resulted in a dose-dependent increase in
      the overflow of dopamine. Not until a sevenfold increase in the level of dopamine
      was seen, the release of acetylcholine was significantly affected. This
      hyporesponsiveness of the striatal cholinergic interneurons to endogenous
      dopamine could not be attributed to dopamine D-1 receptor activation, since no
      effects on striatal acetylcholine release were found by intrastriatal infusions
      of the selective D-1 agonist CY 208-243 or the selective D-1 antagonist SCH
      23390. The results indicate that dopamine D-2 receptors are involved in the
      regulation of striatal acetylcholine release and that these receptors are
      tonically occupied by endogenous dopamine under the present experimental
      conditions 40-48 h after probe implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349161
TI  - Expression of the intercellular adhesion molecule-1 (ICAM-1) in human renal
      allografts and cultured human tubular cells.
AB  - The in vivo distribution of the intercellular adhesion molecule ICAM-1 was
      investigated in renal tissue specimens obtained from 17 renal allotransplanted
      patients, nine normal kidneys (controls), seven native kidneys, nine patients
      with mesangioproliferative glomerulonephritis, and nine patients with active
      extracapillary glomerulonephritis. Biopsies from patients with signs of acute
      rejection showed a significant increase in ICAM-1 expression in the tubular
      epithelium (P less than 0.05). In normal kidneys (controls) ICAM-1 expression was
      found in endothelial cells; additional expression in the tubular epithelial cells
      was induced in patients with extracapillary glomerulonephritis. The in vitro
      expression of ICAM-1 was examined in cultured human tubular cells after
      stimulation with gamma-interferon and interleukin-1, treatment with cyclosporin
      and/or verapamil and coculture with allogenic mononuclear cells. An increased
      ICAM-1 expression was demonstrated by coculture with allogenic mononuclear cells
      and after stimulation with gamma-interferon and/or interleukin-1. Cyclosporin or
      verapamil induced no changes. Our results give support to the hypothesis that
      ICAM-1 upregulation is important in immune interactions such as allograft
      rejection. Furthermore, the in vitro model indicates that ICAM-1 expression is
      regulated by gamma-interferon and interleukin-1 produced by activated T
      lymphocytes and macrophages.

PMID- 1349162
TI  - Analysis of gene amplification in archival tissue by differential polymerase
      chain reaction.
AB  - Oncogene amplification is found in many human tumors, and its detection may have
      important prognostic value. However, analysis of gene amplification may be
      hampered by inadequate tissue or poor DNA quality. We have previously described a
      polymerase chain reaction (PCR)-based procedure called differential PCR that can
      detect variations in gene dosage using miniscule amounts of tumor DNA [Frye,
      R.A., Benz, C.C. & Liu, E. (1989). Oncogene, 4, 1153-1157]. We now report the
      optimization of this technique for the analysis of oncogene amplification in
      paraffin-embedded archival tissues. We find that differential PCR is able to
      detect amplification of the HER2 (c-erbB-2) and the epidermal growth factor
      receptor (EGFR) genes and can be used to arrive at a semiquantitative estimate of
      gene dosage. Furthermore, our approach can determine gene amplification in
      samples in which the DNA is significantly degraded. Using differential PCR on
      paraffin-embedded tissues from cases previously investigated by standard DNA
      extraction and dot-blot procedures, good correlation between the two methods was
      found. Approaches are described to overcome technical problems posed by factors
      that affect the differential PCR, including the method of DNA extraction and
      extreme fragmentation of the DNA (less than 200 base pairs). Furthermore, the
      resulting analytical algorithm reported herein has proved effective in detecting
      oncogene amplification in archival breast cancer specimens from standard
      pathology laboratories. Thus, differential PCR will be particularly helpful in
      the analysis of tumor specimens that are archived, small in size or rare in
      occurrence.

PMID- 1349163
TI  - The HER2 (c-erbB-2) oncogene is frequently amplified in in situ carcinomas of the
      breast.
AB  - Amplification and overexpression of the HER2 (c-erbB-2) oncogene was assessed in
      paraffin-embedded specimens from 27 in situ carcinomas of the breast and from 122
      stage II breast cancers. Gene amplification detected in these archival tissues by
      differential polymerase chain reaction (PCR) was found in 48% of in situ
      carcinomas and in 21% of stage II lesions (chi 2 = 7.62, p less than or equal to
      0.01). In addition, the level of gene amplification correlated with the level of
      HER2 oncoprotein expression as measured by immunohistochemistry for both in situ
      cancers (p less than or equal to 0.025) and stage II cancers (p less than or
      equal to 0.0005). This high incidence of HER2 gene amplification with
      accompanying overexpression in non-invasive breast tumors suggests that
      perturbations of the HER2 oncogene are among the earliest and most common genetic
      lesions in human breast cancer.

PMID- 1349164
TI  - p53 mutations in spontaneously immortalized 3T12 but not 3T3 mouse embryo cells.
AB  - We have asked whether p53 mutations are involved in the process of spontaneous
      immortalization of mouse embryo cells. Cells from Swiss mouse embryos were used
      to prepare 3T3 and 3T12 lines according to the protocol of Todaro & Green
      [(1963). J. Cell Biol., 17, 299-313]. After the cells emerged from crisis, p53
      sequences were amplified by polymerase chain reaction (PCR) from both RNA and
      DNA. The sequence of the aggregated cDNA from each of six 3T3 lines showed no
      evidence of mutation. PCR-amplified p53 cDNA from two 3T3 lines was cloned, and
      individual clones in M13mp19 were partially sequenced. One cell ine showed a
      single, non-coding nucleotide change in 2/8 independent clones. Nine cDNA clones
      from the second 3T3 lines were sequenced, and no single nucleotide changes
      appeared more than once. The mutations which appeared only once were not detected
      in clones of genomic DNA. Since these apparent mutations are probably reverse
      transcriptase or Taq polymerase errors, we conclude that both the 3T3 lines
      contained only wild-type p53. In two out of three independent 3T12 lines however,
      missense mutations were readily observed in the aggregate cDNA sequence.
      Restriction fragment length polymorphism and Southern blot analyses of the
      genomic DNA indicated that these cells were homozygous for the mutations. The p53
      protein molecules in four cell lines were analysed by immunoprecipitation: one
      3T12 line showed the pattern of antibody reactivity characteristic of some p53
      mutants, while the others displayed the wild-type pattern. We conclude that p53
      mutations arise and are strongly selected for during immortalization according to
      the 3T12 but not the 3T3 protocol.

PMID- 1349165
TI  - V-erbA and c-erbA proteins enhance transcriptional activation by c-jun.
AB  - The ability of different transcription factors to interact with one another is an
      important means by which the eucaryotic cell can integrate separate growth and
      differentiation signals into a coherent response. We report here an analysis of
      the interactions of transcription factors that are also the products of
      oncogenes: the erbA, jun and fos proteins. We demonstrate that the c-jun
      polypeptide can functionally interact with the c-erbA protein (thyroid hormone
      receptor) to yield an enhanced activity greater than that of either factor
      individually. Although the avian erythroblastosis v-erbA allele is generally
      thought to act as a transcriptional repressor in vertebrate cells, we also report
      the existence of promoter contexts where v-erbA, as well as c-erbA, can serve as
      'co-activators' of c-jun function. V-erbA appears to augment retinoic acid
      receptor function in the same context. Our results suggest that v-erbA may have
      unanticipated positive effect on transcription in the neoplastic cell in addition
      to the repressor functions previously characterized.

PMID- 1349166
TI  - Continuous subcutaneous infusion of beta 2-agonists in infantile asthma.
AB  - Eleven infants presenting with an asthmatic syndrome were treated with
      subcutaneous infusions of a beta 2-agonist (beta 2A) during an acute episode.
      This treatment was used after difficulties with or failure of beta 2A infusions
      and IV nebulizations. No local or general adverse reactions were observed. The
      serum concentrations of salbutamol obtained at a dose of 0.1 micrograms/kg/min
      were measured in six infants and found to be within the generally accepted
      therapeutic range. This mode of administration proved extremely useful, both by
      itself and as part of a therapeutic protocol, combined with an antibiotic, a
      corticosteroid, and theophylline. It avoids the difficulties of administering
      beta 2A intravenously or by nebulization, while preserving some degree of freedom
      and better general care for the child. The preferred indication is in treatment
      of severe acute asthmatic episodes after failure of nebulizations. The exact
      place in the therapeutic arsenal of infantile asthma remains to be defined.

PMID- 1349167
TI  - Evolving properties of beta-adrenergic receptor antagonists.

PMID- 1349168
TI  - Proliferating cell nuclear antigen in human placenta and trophoblastic disease.
AB  - Expression of proliferating cell nuclear antigen (PCNA), an auxiliary factor for
      the DNA polymerase delta, is closely related to cell proliferation. Using the
      monoclonal anti-PCNA antibody 19F4, we examined the distribution of PCNA in
      formalin-fixed, paraffin-embedded sections of mature and first-trimester
      placentas, 8 hydatidiform moles, and 7 choriocarcinomas. In normal placentas
      there was strong expression of PCNA in cytotrophoblastic nuclei, while the
      syncytium and the amnionic epithelium were PCNA unreactive. Staining of stromal
      cells was variable. These results are in complete agreement with the
      autoradiographic localization of [3H]thymidine incorporation and demonstrate that
      immunoreactivity for PCNA accurately defines areas of proliferative activity in
      routinely processed placental tissues. In choriocarcinomas and hydatidiform moles
      PCNA was predominantly expressed in the cytotrophoblast and intermediate
      trophoblast. Again, the syncytium was largely unreactive for PCNA. These findings
      indicate that even after neoplastic transformation the syncytium has
      comparatively little proliferative activity whereas the mononuclear trophoblastic
      cells divide actively.

PMID- 1349169
TI  - [Serous microcystic adenoma of the pancreas in a 72-year-old woman].

PMID- 1349170
TI  - What drives the translocation of proteins?
AB  - We propose that protein translocation across membranes is driven by biased random
      thermal motion. This "Brownian ratchet" mechanism depends on chemical asymmetries
      between the cis and trans sides of the membrane. Several mechanisms could
      contribute to rectifying the thermal motion of the protein, such as binding and
      dissociation of chaperonins to the translocating chain, chain coiling induced by
      pH and/or ionic gradients, glycosylation, and disulfide bond formation. This
      helps explain the robustness and promiscuity of these transport systems.

PMID- 1349171
TI  - Repression of the beta-amyloid gene in a Hox-3.1-producing cell line.
AB  - Mammalian homeobox genes are widely expressed in the developing central nervous
      system and are postulated to control developmental processes by regulating gene
      expression at the transcriptional level. In vitro studies have identified
      consensus DNA sequences that contain an ATTA core as sites for interaction with
      homeodomain proteins. Such elements have been found in the upstream regulatory
      region of the gene encoding beta-amyloid precursor protein, which is associated
      with the neurological disorder Alzheimer disease. As the beta-amyloid precursor
      protein gene is also expressed in the developing central nervous system and
      appears to play a role in cellular regulatory processes, we have examined the
      possibility that a homeobox gene product can regulate its transcription. We
      demonstrate by Northern blot analyses and transfection experiments that the
      expression of the beta-amyloid precursor protein gene is decreased in cultured
      cells expressing the mouse homeobox gene Hox-3.1.

PMID- 1349172
TI  - Cells that present both specific ligand and costimulatory activity are the most
      efficient inducers of clonal expansion of normal CD4 T cells.
AB  - Clonal expansion of naive CD4 T cells is a necessary step in most adaptive immune
      responses. Two distinct signals are required for clonal expansion to occur,
      ligation of T-cell receptors by an antigenic peptide bound to self major
      histocompatibility complex-encoded class II molecules (signal 1) and a
      costimulatory signal derived from an antigen-presenting cell (signal 2). To study
      whether these two signals need to be delivered by a single cell in order to
      induce clonal expansion of normal CD4 T cells, we have used anti-CD3 bound to Fc
      receptors as a ligand for the T-cell receptor to deliver signal 1 to all CD4T
      cells, and we have inactivated signal 2 with a newly generated monoclonal
      antibody or by using Fc receptor-positive cells that lack the costimulator.
      Costimulation was delivered by cells whose Fc receptors were blocked with anti-Fc
      receptor monoclonal antibody. Our results indicate that delivery of ligand and
      costimulator on one cell is at least 30-fold more efficient than separate
      delivery. No significant clonal expansion was observed when signals 1 and 2 were
      delivered by different cells. We have also carried out experiments using
      fibroblast transfectants that can deliver either or both of these two signals.
      These studies show that separate delivery of these two signals is at least 80
      fold less efficient than their combined delivery by one cell. These findings may
      explain why tissues can express autoantigens and contain active antigen
      presenting cells without inducing autoimmunity.

PMID- 1349173
TI  - Macromolecular assemblage in the design of a synthetic AIDS vaccine.
AB  - We describe a peptide vaccine model based on the mimicry of surface coat protein
      of a pathogen. This model used a macromolecular assemblage approach to amplify
      peptide antigens in liposomes or micelles. The key components of the model
      consisted of an oligomeric lysine scaffolding to amplify peptide antigens
      covalently 4-fold and a lipophilic membrane-anchoring group to further amplify
      noncovalently the antigens many-fold in liposomal or micellar form. A peptide
      antigen derived from the third variable domain of glycoprotein gp120 of human
      immunodeficiency virus type 1 (HIV-1), consisting of neutralizing, T-helper, and
      T-cytotoxic epitopes, was used in a macromolecular assemblage model (HIV-1 linear
      peptide amino acid sequence 308-331 in a tetravalent multiple antigen peptide
      system linked to tripalmitoyl-S-glycerylcysteine). The latter complex, in
      liposome or micelle, was used to immunize mice and guinea pigs without any
      adjuvant and found to induce gp120-specific antibodies that neutralize virus
      infectivity in vitro, elicit cytokine production, and prime CD8+ cytotoxic T
      lymphocytes in vivo. Our results show that the macromolecular assemblage approach
      bears immunological mimicry of the gp120 of HIV virus and may lead to useful
      vaccines against HIV infection.

PMID- 1349175
TI  - Germ-line and somatic p53 gene mutations in multifocal osteogenic sarcoma.
AB  - Multifocal osteogenic sarcoma patients without familial histories of increased
      tumor predisposition were examined for mutations in the highly conserved regions
      of the p53 gene. p53 point mutations were found in tumor DNA from each of the
      four patients we examined. A germ-line p53 mutation was detected in one of these
      patients, and a further rearrangement of the residual wild-type allele was
      detected in tumor tissue. p53 germ-line mutations can contribute to the enhanced
      predisposition to tumor development manifest in patients with multifocal
      osteosarcoma.

PMID- 1349174
TI  - HD-Zip proteins: members of an Arabidopsis homeodomain protein superfamily.
AB  - Homeobox genes encode a large family of homeodomain proteins in animal systems.
      To test whether such genes are also abundant in higher plants, degenerate
      oligonucleotides complementary to sequences encoding the recognition helix (helix
      three) of the homeodomain were used to screen genomic and cDNA libraries from the
      plant Arabidopsis thaliana. Analysis of 8 of the 41 cDNAs isolated revealed that
      each encodes a presumptive homeodomain; interestingly, most of these clones also
      contain a leucine zipper motif tightly linked to the homeodomain. It is concluded
      that Arabidopsis encodes a large family of homeodomain proteins, including
      members that contain a homeodomain/leucine-zipper (HD-Zip) motif.

PMID- 1349176
TI  - The regulation of immunological responses to parasitic infections and the
      development of tolerance.
AB  - It is well established that specific unresponsiveness to immunization can be
      induced by prolonged exposure to antigenic proteins. More generally, many
      parasitic infections, such as the helminth worms and the Leishmania parasites,
      appear to be able to persist in some of their human hosts over long periods of
      time, via what appears to be an ability to induce defective or inappropriate T
      cell responses (= tolerance). Recent research has suggested that cytokines,
      produced by specific subsets of CD4+ T-cells (characterized by cytokine secretory
      profiles and growth properties), have an important, and often complex, role in
      promoting or inhibiting host protective immunity to parasitic infections. By
      examination of the population dynamics of the stimulation and regulation of
      cellular responses to infection, via the use of simple mathematical models, we
      show that nonlinear interactions between CD4+ T-cell subsets and their secreted
      cytokines can result in either host protection or immunological unresponsiveness,
      depending on the magnitude and duration of exposure to parasitic infection.
      Analyses also identify a possible mechanism to explain the stimulation of two
      separate peaks of enhanced T-cell-mediated responses over a wide range of levels
      of antigenic exposure.

PMID- 1349177
TI  - Voltage-dependent block by L-cis-diltiazem of the cyclic GMP-activated
      conductance of salamander rods.
AB  - Block by L-cis-diltiazem of the cyclic GMP-activated conductance was studied in
      excised inside-out patches from the salamander rod outer segment. When L-cis
      diltiazem was applied from the cytoplasmic face of the patch, current suppression
      increased monotonically with membrane depolarization, the ratio of blocked to
      unblocked current varying e-fold in 50 mV. This suggests that L-cis-diltiazem
      interacts with a binding site located about half-way across the membrane field,
      and is unable to fully traverse the cyclic GMP-activated channel. The kinetics of
      block were accelerated by increasing L-cis-diltiazem concentration and by
      depolarization. These results can be fitted by a single barrier model in which
      the barrier peak is located about a third of the way across the membrane field
      from the cytoplasmic face. Application of L-cis-diltiazem from the extracellular
      face of the patch also resulted in an enhancement of block with membrane
      depolarization. Indirect evidence supports the notion that this block resulted
      from partition of the unchanged form of the blocker across the membrane, and its
      subsequent interaction with the cytoplasmic face of the conductance.

PMID- 1349178
TI  - Extracellular cations modulate the ATP sensitivity of ATP-K+ channels in rat
      ventromedial hypothalamic neurons.
AB  - ATP-sensitive K+ (ATP-K+) channels underlie the glucose-sensing nature of
      pancreatic beta-cells by way of their inhibition by intracellular ATP. Recently
      it has been proposed that ATP-K+ channels have a similar function in certain
      hypothalamic neurons that become excitable in raised concentrations of
      extracellular glucose. The aim of this study was to assess the ATP sensitivity of
      ATP-K+ channels in inside-out membrane patches excised from glucose-sensing
      neurons that were acutely isolated from the ventromedial nucleus of rat
      hypothalamus. ATP-K+ channels were less sensitive to ATP in neurons than in other
      tissues. Moreover, the sensitivity of neuronal ATP-K+ channels to inhibition by
      intracellular ATP was modulated by extracellular cations. Under physiological
      ionic gradients (i.e. high extracellular Na+ and low K+), intracellular ATP
      produced a concentration-dependent inhibition of channel activity, with a half
      maximal inhibition (Ki) of 2.32 mM. A non-hydrolysable analogue of ATP, AMP(PNP),
      was similarly effective. In symmetrical K+ (i.e. no extracellular sodium),
      channel activity was tenfold more sensitive to ATP (Ki of 0.21 mM). A parallel
      study on ATP-K+ channels from an insulin-secreting beta-cell line (CRI-G1) showed
      that, in contrast to the neuronal data, extracellular cations had no effect on
      the ATP sensitivity of the channel.

PMID- 1349179
TI  - Fatal association between dieldrin-resistant and susceptible Australian sheep
      blowflies, Lucilia cuprina.
AB  - A novel phenomenon of interactions between genotypes of the dieldrin-resistance
      (Rdl) locus of the Australian sheep blowfly (Lucilia cuprina) is described.
      Susceptible adult flies exposed to dieldrin-resistant (Rdl/Rdl or Rdl/S) adults,
      raised from larvae grown on media containing sublethal concentrations of
      dieldrin, display mortality related to the concentration on which the resistant
      flies developed. The resistant flies excrete quantities of dieldrin that are
      toxic to susceptible flies. These observations provide an additional mechanism to
      those previously identified for the rapid evolution of resistance to dieldrin by
      L. cuprina.

PMID- 1349180
TI  - Chronic hypoxia changes the ratio of endothelin to ATP release from rat aortic
      endothelial cells exposed to high flow.
AB  - Endothelial cells isolated from the thoracic aorta of normoxic and chronically
      hypoxic rats were perfused (0.5 ml min-1) and stimulated by increased flow rate
      (3.0 ml min-1). The release of ATP, endothelin and vasopressin was investigated.
      During periods of high flow rate, endothelial cells isolated from normoxic rats
      increased their release of ATP and endothelin. In comparison, in hypoxic rats,
      ATP release during the period of high flow rate was less, whereas endothelin
      release was greater. Vasopressin release was not increased during periods of
      stimulation in either group of animals. These results suggest that, under
      conditions of reduced arterial oxygen tension, a dynamic balance between ATP and
      endothelin release could regulate the response of vessels to shear stress.

PMID- 1349181
TI  - Smells are no surer: rapid improvement in olfactory discrimination is not due to
      the acquisition of a learning set.
AB  - The claim that rats can demonstrate the 'primate-like' learning capacity of
      learning set formation when trained with olfactory cues, rather than visual or
      auditory cues, has generated considerable interest in recent years. In this
      study, the claim is evaluated in detail by using a series of experimental and
      control procedures to determine whether rats do indeed develop the abstract 'win
      stay, lose-shift' strategy which underlies learning set formation in monkeys. We
      report here that although exposure to a series of novel olfactory discrimination
      problems gives rise to progressive improvement in the rate of learning, it is not
      a necessary condition for the development of that rapid learning. Furthermore,
      even rats which fail to display progressive improvement in olfactory reversal
      learning show rapid learning on novel olfactory discrimination problems. Each of
      these findings suggests that although olfactory learning may be rapid, learning
      set formation does not occur over a short series of problems.

PMID- 1349182
TI  - Sequence divergence and copy number of the middle- and long-wave photopigment
      genes in Old World monkeys.
AB  - We have studied the sequence and organization of the genes for the middle-wave
      (MW) and long-wave (LW) cone photopigment genes in six species of Old World
      monkeys. Previous studies have shown that the MW and LW pigments of all six
      species exhibit peak sensitivities near 535 nm and 565 nm, respectively, and thus
      resemble the equivalent human pigments. In the case of man, the protein
      components of the MW and LW photopigments differ by 15 amino acids, although only
      seven of these differences involve non-homologous substitutions and are therefore
      candidates for a role in spectral tuning. Regions corresponding to exons 4 and 5
      of these genes, and including five such candidate sites, were sequenced in the
      Old World monkeys. In contrast to the equivalent human genes, substitutions were
      found at two of these sites, position 233 and 309 of the MW gene in all six
      species. The role of amino acid substitutions in the spectral tuning of these
      photopigments is discussed. A comparison of the nucleotide sequences of the MW
      and LW genes provides evidence for sequence homogenization within species; the
      role of gene conversion in the evolution of these genes is discussed. The close
      juxtaposition and homology of the MW and LW genes on the X chromosome is thought
      to underlie the high frequency of colour vision defects in man and the presence
      in many individuals of extra copies of the MW gene. A study of a group of
      talapoin (Ceropithecus talapoin) monkeys has revealed a similar numerical
      polymorphism for this gene to that present in man. In contrast to the situation
      in man, where the MW and LW genes may contain a shortened first intron,
      restriction digests of genomic DNA showed that the size of this intron does not
      differ across the six species of Old World monkeys examined.

PMID- 1349183
TI  - Transient presence and functional interaction of endogenous GABA and GABAA
      receptors in developing rat optic nerve.
AB  - GABA (gamma-aminobutyric acid) is a major inhibitory synaptic neurotransmitter
      with widespread distribution in the central nervous system (CNS). GABA can also
      modulate axonal excitability by activation of GABAA receptors in CNS white matter
      regions where synapses and neuronal cell bodies are not present. Studies on
      cultured glia cells have revealed the synthesis of GABA in rat optic nerve O-2A
      progenitor cells that give rise to oligodendrocytes and type 2 astrocytes in
      vitro. We report here that: (i) GABA is detected by immuno-electron microscopy in
      intact rat optic nerve and is localized to glia and pre-myelinated axons during
      the first few weeks of postnatal development, but is markedly reduced or absent
      in the adult; and (ii) neonatal optic nerve is depolarized by GABAA receptor
      agonists or by the inhibition of GABA uptake. These results demonstrate the
      presence of functional GABAA receptors, and GABA uptake and release mechanisms in
      developing rat optic nerve, and suggest that excitability of developing axons can
      be modulated by endogenous neurotransmitter at non-synaptic sites.

PMID- 1349184
TI  - Parasitic helminth infection and cognitive function in school children.
AB  - The study examines the effect of moderate to high worm burdens of Trichuris
      trichiura infection on the cognitive functions of 159 school children (age 9-12
      years) in Jamaica, using a double-blind placebo-controlled protocol. Results were
      evaluated by using a forward-stepwise multiple linear regression. Removal of
      worms led to a significant improvement in tests of auditory short-term memory (p
      less than 0.017; p less than 0.013), and scanning and retrieval of long-term
      memory (p less than 0.001). Nine weeks after treatment, there were no longer
      significant differences between the treated children and an uninfected Control
      group in these three tests of cognitive function. It is concluded that whipworm
      infection has an adverse effect on certain cognitive functions which is
      reversible by therapy.

PMID- 1349186
TI  - Sperm size and sperm competition in birds.
AB  - In a sample of 20 species of North American passerine birds we found no relation
      between sperm size and mating system like that previously reported in mammals
      (Gomendio & Roldan (Proc. R. Soc. Lond. B 243, 181 (1991)). Instead, we found a
      positive correlation between sperm length and the length of female sperm storage
      tubules (SSTS) and a negative correlation between sperm length and the number of
      SSTS. Both of these correlations suggest that the more than fivefold variation in
      sperm size we found among species can be explained by sperm competition for
      access to storage sites (SSTS) in females. As longer sperm appear to be able to
      swim faster, selection should favour long sperm when SSTS are in short supply;
      sperm long enough to fill an SST might also prevent access to SSTS by the sperm
      of other males. Conversely, selection should favour shorter sperm when there is
      an advantage to sperm layering within an SST promoting a last-male mating
      advantage. Although we conclude that sperm competition influences sperm size in
      birds, little is known about the interactions between sperm and SSTS. It seems
      clear, however, that detailed study of this interaction will provide a new
      dimension to the study of avian mating systems.

PMID- 1349185
TI  - The ontogeny of peroxisome-proliferator-activated receptor gene expression in the
      mouse and rat.
AB  - The expression of the gene coding for peroxisome-proliferator-activated receptor
      (PPAR), a novel transacting factor belonging to the steroid superfamily, has been
      determined in the mouse and rat throughout development using hybridization
      histochemistry. Messenger RNA is demonstrable in the liver and brown fat from the
      fetal period onwards and, additionally, in the heart, kidney and gut post
      natally. It is proposed that the upregulation of transcription of peroxisomal
      beta oxidation genes in specific tissues follows binding of the receptor to its
      natural ligand. Thus PPAR may have an important role in cold adaptation and non
      shivering thermogenesis as well as in detoxification.

PMID- 1349187
TI  - Voltage responses to tones of outer hair cells in the basal turn of the guinea
      pig cochlea: significance for electromotility and desensitization.
AB  - Voltage responses were recorded from outer hair cells (OHCS) in the basal coil of
      the guinea-pig cochlea in response to tones at frequencies above the
      characteristic frequency (CF) presented together with a 100 Hz tone at 80 dB or
      85 dB sound pressure level (SPL). The amplitude and polarity of voltage responses
      to a 100 Hz, 85 dB SPL tone were altered when presented together with tones at
      frequencies above CF according to the frequency and level of the high-frequency
      tone, OHC phasic (ac) (greater than 500 microV) but not tonic (dc) voltage
      responses were elicited by the high-frequency tone. Thus the responses of OHCS to
      low-frequency tones can be altered when presented together with a high-frequency
      tone without an apparent dc change in membrane potential. Recordings were made
      from an OHC during cochlear desensitization through exposure to an intense tone.
      The maximum voltage response to high-level low-frequency tones remained
      unchanged, although the OHC response to high-frequency tones became less
      sensitive to low-level stimuli and more linear as a function of level. It is
      suggested that desensitization is associated with a change in the mechanical
      properties of the cochlea, possibly associated with the OHCS themselves, and not
      with inactivation of the transducer channels. The amplitude of the OHC ac voltage
      response was measured at neural threshold, and the consequences of these
      measurements on hair cell electromotility are considered.

PMID- 1349188
TI  - Effects of selective denervation and nerve growth factor on activity-mediated
      growth of rat parotid gland.
AB  - A dietary change from all liquid to solid food is followed by an average increase
      of 200% in [3H]thymidine uptake into the parotid gland of rat. However, removal
      of either the parasympathetic (Px) or the sympathetic (Sx) innervation to the
      parotid gland prior to the dietary change resulted in a partial inhibition of the
      increase; values for the parasympathectomized gland were 51% of those of the
      innervated gland, and values of the sympathectomized parotid gland were 42% of
      those of the innervated gland. Removal of both autonomic nerves caused a complete
      inhibition. Initiation of nerve growth factor (NGF) injection (1 microgram/kg
      body wt, two times daily for the 2 days of chow refeeding) at the time of chow
      refeeding had no effect on completely or partially denervated glands, and
      thymidine values for the denervated parotid gland of rats given NGF did not
      differ statistically from those of rats not given NGF. With parasympathectomy,
      sympathectomy, and complete denervation, weight of parotid gland was decreased
      from that of innervated glands, and administration of NGF had no effect on the
      denervation-induced decreases. The data show that both branches of the
      innervation to parotid gland must be intact to ensure a maximal increase in
      thymidine uptake with the dietary change from liquid to solid food. The level of
      the enzyme, beta 1-4 galactosyltransferase, involved in proliferation, also
      depended on the presence of intact nerves. Enzyme activity of innervated parotid
      gland showed an average increase of 200% with chow refeeding of rats previously
      on liquid diet, but with Px, the average increase was 51% of that of the
      innervated parotid, and with Sx, it was 41%. NGF administration did not cause any
      change in levels of this enzyme in any Px or PxSx parotid gland and only a small
      change in Sx parotid; it did increase levels of this enzyme in parotid of rats
      without submandibular-sublingual glands.

PMID- 1349189
TI  - Biological activity and receptor binding characteristics to various human tumors
      of acetylated somatostatin analogs.
AB  - Several somatostatin analogs with recently synthesized acetylated N terminus were
      assayed in vivo for their effects on sodium pentobarbital-stimulated growth
      hormone (GH) levels in fed male rats and gastrin-releasing peptide (14-27)
      stimulated gastrin levels in fasted male rats. The binding characteristics of
      these analogs to somatostatin receptors were also examined in various human
      tumors and normal tissues. The analog RC-101-I, injected at a dose of 0.1
      micrograms/100 g body wt, significantly suppressed GH release (P less than 0.01)
      for at least 2 hr. Analog RC-160-II caused the longest inhibition of GH release,
      greater than that induced by nonacetylated parent analog RC-160, with GH levels
      showing significant suppression (P less than 0.01) for more than 3 hr. Analogs RC
      160-II and RC-101-I and RC-160, injected at a dose of 1.0 micrograms/100 g body
      wt, significantly (P less than 0.01) suppressed gastrin-releasing peptide (14-27)
      stimulated serum gastrin. Analog RC-101-I was active in this test at a dose of
      0.1 micrograms/100 g body wt. RC-160-II showed significant binding to
      somatostatin-14 receptors in all investigated tissues (human colon, human colon
      cancer, breast cancer, human pancreas and pancreatic cancer, human prostate and
      prostate cancer, and rat cerebral cortex), but there were marked variations in
      binding affinities among various normal and cancerous tissues. The highest
      affinity was found in membranes of colon cancer (Ka = 18.4 nM-1) and breast
      cancer (Ka = 12.46 nM-1). The binding affinity of RC-160-II to somatostatin
      receptors in membranes of the breast cancer was similar to that of RC-160. RC-101
      I showed higher binding affinity to somatostatin-14 receptors than RC-160 in
      human breast, pancreatic, and prostate cancer. With the exception of breast
      cancer tissue, the binding affinity of RC-101-I was significantly lower than that
      of RC-160-II in membranes of all investigated tissues. It can be concluded that
      acetylated somatostatin analogs RC-101-I and RC-160-II possess prolonged and
      enhanced biological activities in suppressing serum GH and gastrin in rats.
      Significant variations in binding affinities for these analogs in different
      tissues and various tumors suggest that differences may exist between
      somatostatin receptors in normal versus malignant tissues. This raises the
      possibility that some of these analogs could be used more selectively in the
      treatment of various neoplasms.

PMID- 1349190
TI  - Effects of adrenoceptor blockade on cardiac hypertrophy and myocardial
      phospholipids.
AB  - Catecholamines have been proposed as a stimulus for the hypertrophic response to
      pressure overload of the heart and could also mediate the membrane lipid changes
      associated with cardiac hypertrophy. To address both of these possibilities,
      cardiac hypertrophy was induced by aortic constriction in the presence or absence
      of chronic alpha- or beta-adrenoceptor blockade. Heart weights and heart weight
      to body weight ratios in aortic-constricted rats of the adrenoceptor-blocked and
      vehicle-treated groups were elevated to the same extent when compared with values
      in sham-operated rats of each group. Analysis of the fatty acyl composition of
      the major phospholipid classes revealed that similar changes occurred in vehicle
      treated, alpha-blocked, and beta-blocked aortic-constricted rats when compared
      with respective groups of sham-operated rats. Specifically, linoleic acid was
      reduced in the phosphatidylcholine, phosphatidylethanolamine (PE), and
      cardiolipin (CL) fractions in all groups of aortic-constricted rats. This
      reduction was accompanied by increased docosahexaenoic acid, arachidonic acid, or
      palmitic acid in phosphatidylcholine; docosahexaenoic acid in
      phosphatidylethanolamine; and oleic acid in cardiolipin fractions. Adrenoceptor
      blockade did not prevent or attenuate the major changes in the fatty acyl
      composition of phospholipids or the increase in heart weight associated with
      aortic constriction. This suggests that a change in the level of adrenoceptor
      stimulation is not the stimulus for cardiac hypertrophy or the observed
      alterations in phospholipid composition in the pressure-overloaded rat heart.

PMID- 1349192
TI  - Annual meeting of the Swedish Society for Rheumatology during "Riksstaman". 27-29
      November 1991. Abstracts.

PMID- 1349191
TI  - Endopeptidase 24.15 inhibition and opioid antinociception.
AB  - Whereas endopeptidase 24.11 cleaves the Gly-Phe bond in both Met- and Leu
      enkephalin, endopeptidase 24.15 rapidly converts dynorphin A1-8, alpha and beta
      neoendorphin into Leu-enkephalin, and Met-enkephalin-Arg6-Gly7-Leu8 (MERGL) into
      Met-enkephalin. Inhibitors of both endopeptidase 24.11 and endopeptidase 24.15
      each produce antinociception, and inhibitors of endopeptidase 24.11 increase the
      magnitude of enkephalin antinociception. The present study compared the central
      antinociceptive effect of an inhibitor of endopeptidase 24.15, N-[1-(R-S)-carboxy
      3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB) with one of
      endopeptidase 24.11 N-[1-(RS)-carboxy-3-phenylpropyl]-Phe-p-aminobenzoate (cFP-F
      pAB) upon central opioid antinociception induced by MERGL, metenkephalin and
      dynorphin A1-8. cFP-AAF-pAB, but not cFP-F-pAB increased MERGL antinociception on
      the tail-flick and jump tests. In contrast, cFP-F-pAB, but not cFP-AAF-pAB
      increased met-enkephalin antinociception. Whereas central dynorphin A1-8 failed
      to induce antinociception itself, co-administration of cFP-AAF-pAB and dynorphin
      A1-8 increased nociceptive thresholds. This effect was not accompanied by motor
      dysfunction, but was blocked by systemic pretreatment with naloxone or central
      pretreatment with naltrexone or nor-binaltorphamine, but not beta-funaltrexamine.
      These data indicate that endopeptidase 24.15 may be responsible for the
      degradation of specific opioid peptides (e.g., MERGL, dynorphin), and that this
      process may prevent the full expression of their antinociceptive properties.

PMID- 1349193
TI  - [Food allergies: many complaints, few realities].

PMID- 1349194
TI  - [Various genetic aspects of X-linked mental retardation].
AB  - X-Linked Mental Retardation constitutes an important pathologic entity in
      genetics. The overall significance, history and background of the concept of X
      Linked mental retardation is reviewed with a special mention to the cases
      referenced under the term non-specific X-Linked mental retardation. The concept
      of lod-score has brought some improvement in the clinical delineation of the X
      Linked mental retardation syndromes with some recent reports of suggestive
      linkage studies. The fragile-X syndrome is discussed with a special focus on
      reports of X-linked mental retardation with X chromosomal deletions or
      duplications. Linkage and molecular studies are reported viewing genetic
      approaches based on restriction fragment length polymorphisms. DNA probes
      spanning the length of the X and Y chromosomes which may prove critical to the
      development of diagnostic tests are referred. Computer assistance for a
      compilation of clinical findings in the X-linked mental retardation syndromes is
      specified as a diagnostic review and assistance program to check on the various
      entities. A joint collaborative investigation is reported to ascertain families
      with X-linked mental retardation in order to develop direct and linkage studies
      for the diagnosis of there disorders.

PMID- 1349195
TI  - Investigation of the mode of inheritance of insulin-dependent diabetes mellitus
      in Japanese subjects.
AB  - Previous studies have shown that insulin-dependent diabetes mellitus is
      positively associated with HLA-DR4 and HLA-DR9 in Japanese populations. It was
      proposed that susceptibility to the disease is determined by a single HLA allele
      associated with both DR4 and DR9. DR genotypes in a Japanese population with
      insulin-dependent diabetes mellitus were determined by DRB/DQB RFLP analysis. A
      single disease-susceptibility-allele model was tested by the antigen-genotype
      frequency-among-patients method. Recessive and additive inheritance of a single
      susceptibility allele were rejected. The DR9-associated disease-susceptibility
      allele in Japanese subjects is distinct from both the DR3- and DR4-associated
      susceptibility alleles in white Caucasians. The data suggest further complexity
      in the inheritance of HLA-associated susceptibility to insulin-dependent diabetes
      mellitus.

PMID- 1349196
TI  - DNA mutations associated with the human butyrylcholinesterase J-variant.
AB  - The J-variant of human serum butyrylcholinesterase (BChE) causes both an
      approximately two-thirds reduction of circulating enzyme molecules and a
      corresponding decrease in the level of BChE activity present in serum. Since the
      level of serum BChE activity and the duration of succinylcholine apnea are
      inversely correlated, this marked decrease in activity makes individuals with the
      J-variant more susceptible than usual subjects to prolonged apnea from
      succinylcholine. We reinvestigated the same family in which Garry et al.
      identified the J-variant phenotype. The atypical, fluoride, and K-variant
      mutations were also identified in members of the 47-person pedigree. DNA
      amplification by PCR, followed by direct sequencing of the amplified DNA, led to
      the finding that the J-variant phenotype of human serum BChE was associated with
      two DNA point mutations in the coding region. One of these was the mutation
      previously identified with the K-variant phenotype (GCA----ACA; Ala539----Thr).
      The other was an adenine-to-thymine transversion at nucleotide 1490, which
      changed amino acid 497 from glutamic acid to valine (GAA----GTA; Glu497----Val).
      This latter point mutation was named the J-variant mutation (formal name
      BCHE*497V). The J-variant mutation has not been identified without the K-variant
      mutation. The J-variant mutation created an RsaI-enzyme RFLP. Two additional
      point mutations, located in the noncoding regions of the gene, were also found to
      be linked with the J-variant and K-variant point mutations on the same allele.
      These noncoding polymorphic mutations had previously been found linked to the
      atypical and K-variant point mutations. A summary table shows dibucaine,
      fluoride, and Hoffmann-La Roche compound Ro 2-0683 inhibition numbers for 119
      samples whose DNA has been sequenced. Eighteen BChE genotypes are represented.

PMID- 1349197
TI  - Nonsynonymous polymorphic sites in the apolipoprotein (apo) A-IV gene are
      associated with changes in the concentration of apo B- and apo A-I-containing
      lipoproteins in a normal population.
AB  - The aims of this study were to detect polymorphic sites in the apolipoprotein
      (apo) A-IV gene, to establish their frequencies, to determine potential
      haplotypes, and to investigate the role of these polymorphisms in lipid
      metabolism. A sequencing study of four individuals led to the identification of
      two synonymous mutations (codons 9 and 54) and three nonsynonymous mutations (Val
      8----Met, Gln360----His, and Thr347----Ser) and of a VNTR polymorphism within a
      series of three or four CTGT repeats in the noncoding region of exon 3.
      Frequencies of these polymorphisms were determined in 291 students by using
      naturally occurring (BstEII for the synonymous mutation in codon 54, HinfI for
      Thr347----Ser, and Fnu4HI for Gln360----His) or artificially introduced
      restriction-enzyme cutting sites (BstEII for the synonymous mutation in codon 9
      and MamI for Val-8----Met), subsequent to PCR amplification. The four-base
      deletion/insertion polymorphism and its localization cis or trans to the
      mutations in codons 347 and 360 were studied by direct sequencing of PCR
      amplified DNA from 87 students. Frequencies of the rarer alleles were .007 for
      apo A-IV-8:Met, .04 for the synonymous mutation in codon 9, .14 for the
      synonymous mutation in codon 54, .16 for apo A-IV347:Ser, .07 for apo A
      IV360:His, and .39 for the four-base of insertion. Apo A-IV360:His in all cases
      was cis-localized to the (CTGT)3 repeat and apo A-IV347:Thr; and apo A-IV347:Ser
      was cis-localized to the (CTGT)4 repeat and apo A-IV360:Gln. Four haplotypes
      formed from these three polymorphic sites were thus found. The apo A-IV347:Ser
      allele was associated both with significantly lower plasma apo B concentrations
      in both sexes and with significantly lower LDL-cholesterol concentrations in men.
      Heterozygous carriers of apo A-IV360:His exhibited significantly higher
      concentrations of LDL-cholesterol and lower Lp(a) concentrations, compared with
      apo A-IV360:Gln homozygotes. We could not confirm the previously reported
      association of apo A-IV360:His with elevated HDL-cholesterol concentrations. In
      the population, the Val-8----Met polymorphism was not associated with
      significantly different lipid concentrations, but in a family study the Met-8
      allele was associated with lower HDL-cholesterol and higher LDL-cholesterol
      concentrations. In conclusion, our results indicate an important role of the apo
      A-IV gene locus in the metabolism of apo B and, to a lesser extent, apo A-I
      containing lipoproteins.

PMID- 1349199
TI  - A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions
      of 22q11.
AB  - DiGeorge syndrome (DGS), a developmental field defect of the third and fourth
      pharyngeal pouches, is characterized by aplasia or hypoplasia of the thymus and
      parathyroid glands and by conotruncal cardiac malformations. Cytogenetic studies
      support the presence of a DGS critical region in band 22q11. In the present
      study, we report the results of clinical, cytogenetic, and molecular studies of
      14 patients with DGS. Chromosome analysis, utilizing high-resolution banding
      techniques, detected interstitial deletions in five probands and was inconclusive
      for a deletion in three probands. The remaining six patients had normal
      karyotypes. In contrast, molecular analysis detected DNA deletions in all 14
      probands. Two of 10 loci tested, D22S75 and D22S259, are deleted in all 14
      patients. A third locus, D22S66, is deleted in the eight DGS probands tested.
      Physical mapping using somatic cell hybrids places D22S66 between D22S75 and
      D22S259, suggesting that it should be deleted in the remaining six cases. Parent
      of-origin studies were performed in five families. Four probands failed to
      inherit a maternal allele, and one failed to inherit a paternal allele. On the
      basis of these families, and of six maternally and five paternally derived
      unbalanced-translocation DGS probands in the literature, parent of origin or
      imprinting does not appear to play an important role in the pathogenesis of DGS.
      Deletion of the same three loci in all 14 DGS probands begins to delineate the
      region of chromosome 22 critical for DGS and confirms the hypothesis that
      submicroscopic deletions of 22q11 are etiologic in the vast majority of cases.

PMID- 1349198
TI  - Waardenburg syndrome (WS) type I is caused by defects at multiple loci, one of
      which is near ALPP on chromosome 2: first report of the WS consortium.
AB  - Previous studies have localized the gene for Waardenburg syndrome (WS) type I to
      the distal portion of chromosome 2q, near the ALPP locus. We pooled linkage data
      obtained from 41 WS type I and 3 WS type II families which were typed for six
      polymorphic loci on chromosome 2q in order to refine the location of the WS locus
      (WS1) and evaluate the extent of genetic heterogeneity. In the course of this
      work, we developed diagnostic criteria for genetic and phenotypic studies. Our
      findings, based on two-locus and multilocus analysis using a linkage map
      established from reference pedigrees, suggest that there are two or more
      mutations causing WS, one of which (i.e., WS1) is located on chromosome 2q,
      between the ALPP and FN1 loci, at distances of 7.8 cM and 11.2 cM for each
      marker, respectively. The results also indicate that WS1 is responsible for the
      illness in approximately 45% of all families in this sample. However, the odds
      favoring this position over a location between ALPP and SAG are only 2:1 when
      alternate assumptions about the proportion of linked families are considered. We
      conclude that a more saturated map of this region of chromosome 2q, including
      highly polymorphic markers, will be needed to accurately distinguish linked
      families and, ultimately, isolate the mutant gene.

PMID- 1349200
TI  - Confirmation and refinement of the genetic localization of the Coffin-Lowry
      syndrome locus in Xp22.1-p22.2.
AB  - The Coffin-Lowry syndrome (CLS) is an X-linked inherited disease of unknown
      pathogenesis characterized by severe mental retardation, typical facial and
      digital anomalies, and progressive skeletal deformations. Our previous linkage
      analysis, based on four pedigrees with the disease, suggested a localization for
      the CLS locus in Xp22.1-p22.2, with the most likely position between the marker
      loci DXS41 and DXS43. We have now extended the study to 16 families by using
      seven RFLP marker loci spanning the Xp22.1-p22.2 region. Linkage has been
      established with five markers from this part of the X chromosome: DXS274 (lod
      score [Z] (theta) = 3.53 at theta = .08), DXS43 (Z(theta) = 3.16 at theta = .08),
      DXS197 (Z(theta) = 3.03 at theta = .05), DXS41 (Z(theta) = 2.89 at theta = .08),
      and DXS207 (Z(theta) = 2.73 at theta = .13). A multipoint linkage analysis
      further placed, with a maximum multipoint Z of 7.30, the mutation-causing CLS
      within a 7-cM interval defined by the cluster of tightly linked markers (DXS207
      DXS43-DXS197) on the distal side and by DXS274 on the proximal side. Thus, these
      further linkage data confirm and refine the map location for the gene responsible
      for CLS in Xp22.1-p22.2. As no linkage heterogeneity was detected, this validates
      the use of the Xp22.1-p22.2 markers for carrier detection and prenatal diagnosis
      in CLS families.

PMID- 1349201
TI  - Formulary designation of cimetidine as the primary intravenous histamine H2
      receptor antagonist.

PMID- 1349202
TI  - Evidence for linkage between the swine L blood group and the loci specifying the
      receptors mediating adhesion of K88 Escherichia coli pilus antigens.
AB  - Brush borders or enterocytes obtained from the small intestine of 248 pedigreed
      pigs were tested by adhesion assay in vitro with enterotoxigenic Escherichia (E.)
      coli strains, each expressing one of the three K88 pilus variants K88ab, K88ac
      and K88ad. All pigs were classified as belonging to one of the four adhesion
      phenotypes: I--K88ab(-), ac(-), ad(-); II--K88ab(-), ac(-), ad(+); III--K88ab(+),
      ac(+), ad(-); and IV--K88ab(+), ac(+), ad(+). Serum or red cells were typed for
      15 blood group systems: A-O, B, C, D, E, F, G, H, I, J, K, L, M, N and O; for 11
      biochemical polymorphisms: PI1, PI2, PO1A, A1BG, GPI, PGD, TF, HPX, ADA, PGM and
      AMY; the polymorphism at the IGHG1 locus. Linkage analysis was performed between
      the alleles at the locus (loci) specifying K88 receptors able to bind one or more
      different serological types of K88 E. coli and alleles for markers at other loci.
      Linkage was demonstrated between the locus for the L blood group system and the
      locus (loci) for K88 E. coli receptors (Z = 3.24), adding one locus (loci) to the
      previously identified linkage group IV (LGIV) [L-SLB]. The maximum likelihood
      estimate of the recombination fraction (theta) was 0.23. No evidence was found
      for linkage between any of the other biochemical and immunogenetic markers and
      the receptor locus (loci) of K88 E. coli.

PMID- 1349204
TI  - Synteny mapping of the bovine IGHG2, CRC and IGF1 genes.
AB  - A panel of bovine-murine hybrid cell lines was analysed for 10 loci, including
      three (IGF1, IGHG2 and the calcium release channel gene [CRC]) that have
      previously been mapped in man, but not in cattle. The IGF and CRC genes were
      indirectly mapped to chromosomes 5 and 18 respectively and the syntenies of the
      HOX2 and GH genes and of the NP and FOS genes were confirmed. The results also
      show that the IGHG2 locus, which is linked to NP and FOS on human chromosome 14,
      is separated from these genes in cattle. By showing synteny of the IGHG2 and MPI
      loci, the IGHG2 locus has been indirectly mapped to chromosome 21.

PMID- 1349205
TI  - A PvuII restriction fragment length polymorphism at the ovine uncoupling protein
      locus.

PMID- 1349203
TI  - Analysis of immunoglobulin light chain loci in sheep.
AB  - A sheep kappa cDNA probe was isolated, characterized by sequence analysis and
      shown to have significant sequence identity to other kappa light chains. This
      probe and a sheep lambda light chain probe were used to estimate the extent of
      various sheep immunoglobulin light chain gene loci by Southern blot analysis of
      genomic DNA. The results showed that the sheep has a single hybridizing kappa
      constant gene and three to five kappa V segment bands. Segregation of three
      polymorphic bands at the lambda C locus indicated that they were products of
      separate C segments. Restriction fragment pattern variations were obtained using
      light chain probes on various sheep breeds, but no pattern or individual band was
      characteristic for a particular breed.

PMID- 1349206
TI  - A PvuII polymorphism at the ovine corticotrophin releasing hormone (CRH) locus.

PMID- 1349207
TI  - Revascularization for coronary ostial stenosis in Takayasu's disease with
      calcified aorta.
AB  - A case in which a patient with stenoses of the right and left coronary ostia and
      heavy calcification of the aorta caused by Takayasu's disease was successfully
      treated by coronary artery bypass grafting is presented. The aortic ends of the
      two grafts were attached to a xenopericardial patch, which was sutured into the
      ascending aorta. This technique can be done without fine sutures, which are
      required for proximal anastomosis of a vein graft, and may reduce the risk of
      ostial stenosis.

PMID- 1349209
TI  - On the issue of drug washout prior to polysomnographic studies in depressed
      patients.
AB  - In psychoneurobiological studies it is a point of controversy how long
      psychoactive medication has to be withdrawn to exclude drug effects on the
      variables to be investigated. In order to answer the question of whether the
      generally assumed two-week washout of psychoactive medication is sufficient for
      polysomnographic studies, we computed a post hoc analysis of EEG sleep recordings
      in 61 newly admitted depressed patients. The results indicate that after a 2-week
      withdrawal of tricyclic antidepressants and/or benzodiazepines there are no major
      drug effects on visually scored polysomnograms. In addition, the observations
      raise the question of whether even a 1-week drug washout may be sufficient to
      exclude confounding effects of prior psychoactive medication on EEG sleep.

PMID- 1349210
TI  - Extrapyramidal signs in Alzheimer's disease: a 3-year follow-up study.
AB  - Occurrence of extrapyramidal signs was investigated in a follow-up study of 32
      patients with probable Alzheimer's disease (AD). Bradykinesia and rigidity were
      observed in 39% and 11% of the neuroleptic-free patients at entry and in 72% and
      61% at year 3, respectively. Tremor was not a predominant feature nor did its
      occurrence increase over time. Use of neuroleptics contributed to extrapyramidal
      signs; 75-100% of the neuroleptic-treated patients showed bradykinesia, rigidity
      or orofacial dyskinesia. The homovanillic acid (HVA) concentrations of the
      cerebrospinal fluid at entry were comparable to those of age-matched controls.
      Nor did HVA levels correlate with rigidity or bradykinesia in these early AD
      cases. Presence of bradykinesia or rigidity at the initial evaluation predicted
      more severe dementia and a poor prognosis over the period of 3 years, although
      interaction of initial clinical severity of dementia was significant. Of 15
      patients with these signs 3 (20%) died and 8 (53%) needed institutional care,
      while of 17 patients without these signs only 1 (6%) died and 2 (12%) were
      institutionalized by year 3 (p less than 0.01).

PMID- 1349208
TI  - Borna disease virus-infected astrocytes function in vitro as antigen-presenting
      and target cells for virus-specific CD4-bearing lymphocytes.
AB  - Astrocytes isolated from the brain of newborn Lewis rats and an astrocytic cell
      line were susceptible to infection with the neurotropic Borna disease virus in
      vitro. Since astrocytes also have been found to be infected in vivo it seemed
      appropriate to test this cell type for interaction with a Borna disease virus
      specific CD4+ T cell line. Borna disease virus-infected astrocytes were found to
      be capable of presenting virus-specific antigen to virus-specific T cells in
      vitro. However, the response was significantly enhanced if the purified 38/39kDa
      Borna disease virus-specific protein was added exogenously to the cultures.
      Beside the function as antigen-presenting cells for various antigens including
      virus-specific protein and myelin basic protein, persistently infected astrocytes
      were also found to act as target cells for a CD4+ T cell line as shown in
      conventional 51Cr release assays after induction of MHC class II expression by
      gamma interferon. Infection of astrocytes alone did not cause expression of this
      self antigen. It could be shown that the ability of CD4+ BDV-specific T cells to
      mediate lysis was in part dependent on the stage of activation. Lymphocytes
      "activated" before testing exerted high lysis after only 4h of coincubation with
      target cells, whereas "resting" T cells did not cause significant lysis until 12h
      of coincubation. The dependence of the interaction between effector and target
      cells on MHC class II antigen was demonstrated by the finding that antibodies to
      Ia antigens reduced lysis of target cells.

PMID- 1349211
TI  - Tyrosine hydroxylase-like (TH) immunoreactivity in Parkinson's disease and
      Alzheimer's disease.
AB  - We used tyrosine hydroxylase immunoreactivity (TH) to mark dopaminergic fibers in
      cerebral tissue from adult persons with Parkinson's disease (PD) or Alzheimer's
      disease (AD). In the PD cases we found a loss of dopaminergic neurons in the
      ventral tegmental area (VTA), severely reduced TH fibers in dopaminergic terminal
      fields (particularly in the hippocampal perforant pathway) and neurofibrillary
      tangles (NFT), that occurred only in the perforant pathway. In contrast, AD cases
      were characterized by a lack of significant neuron loss in the VTA and by mild
      loss of TH fibers. A decreased dopaminergic innervation of the perforant pathway
      in cases of PD appears to be associated with the occurrence of NFT in these
      structures.

PMID- 1349212
TI  - The effects of alpha-2 adrenoceptor antagonist, atipamezole, on spatial learning
      in scopolamine-treated and aged rats.
AB  - In order to study whether noradrenergic drugs improve age-related cognitive
      dysfunctions the present experiments investigated whether atipamezole, a
      selective and specific alpha-2 antagonist, improves spatial learning impairment
      due to cholinergic blockade (scopolamine 0.8 mg/kg) or aging in rats. Previously,
      it has been shown that atipamezole dose-dependently (0.03-3.0 mg/kg) increases
      the turnover of noradrenaline in rat brain. According to the present results,
      atipamezole (0.1, 0.3, 0.6 mg/kg) did not affect spatial learning/memory when
      assessed in a free swim trial of the water maze task in control rats.
      Furthermore, atipamezole (0.1, 0.6 mg/kg) did not improve learning deficit in
      scopolamine treated young rats. Higher doses (greater than or equal to 1.0 mg/kg)
      of atipamezole could not be tested, because they induce floating behaviour in
      rats. In aged rats, which were screened to be impaired in the initial acquisition
      of the water maze task, 0.3 mg/kg atipamezole impaired further learning of this
      task. Because previous studies suggest that age-related learning impairment in
      the water maze may be, at least partly, due to a cholinergic deficit, the present
      results suggest that atipamezole which increases the release of noradrenaline in
      brain does not alleviate this learning deficit.

PMID- 1349213
TI  - Production of single-stranded DNA for sequencing: an alternative approach.
AB  - We describe a simple procedure for the direct sequencing of single-stranded, PCR
      amplified, target regions of human genomic DNA. At variance with previously
      reported procedures, purification of the desired double-stranded DNA was
      introduced. This additional step allowed the single-stranded amplification and
      sequencing of the target gene. This step is required for direct sequencing of
      some amplified regions of human genomic DNA. However, no individual technique
      seems suitable to generate and sequence all single-stranded DNA.

PMID- 1349214
TI  - [Takayasu disease: an unusual form of presentation].

PMID- 1349215
TI  - Drug interaction between rifampicin, isoniazid and cotrimoxazole in rabbits.
AB  - 1 The results of cotrimoxazole (CTZ) co-administration (15 mg kg-1 trimethoprim +
      40 mg kg-1 sulphamethoxazole) on plasma concentration and various pharmacokinetic
      parameters of rifampicin (RIF, 24 mg kg-1) and isoniazid (INH, 14 mg kg-1) were
      studied. 2 In the test group (n = 6), CTZ was administered on the 24th day of
      antitubercular treatment (ATT) and given for 7 d. 3 At the end of concurrent
      treatment with CTZ, RIF half-life (t1/2) and plasma concentration were both
      increased. However, there was no effect on INH half-life and plasma
      concentration.

PMID- 1349216
TI  - Interindividual variations in enzymes controlling organophosphate toxicity in
      man.
AB  - 1 Interindividual variations in an unexposed population have been defined for
      five enzymes involved in organophosphate (OP) toxicity. The enzymes measured
      were: red blood cell acetylcholinesterase (AChE), lymphocyte neuropathy target
      esterase (NTE), serum cholinesterase (ChE), serum paraoxonase and serum
      arylesterase. 2 AChE and arylesterase were normally distributed in the population
      whilst the distribution of NTE, ChE and paraoxonase deviated significantly from
      normal. 3 Assay precision and intra-individual variability were measured for each
      of the enzymes; the effect on interindividual variation was assessed. 4
      Variations in enzyme activities between individuals could have profound effects
      on susceptibility to OP toxicity. Prior determination of these enzymes may be
      predictive of susceptibility. 5 Lymphocyte NTE has some limitations as an
      indicator of exposure to neurotoxic OPs.

PMID- 1349217
TI  - Prevention of chloroquine absorption by activated charcoal.
AB  - 1. The ability of activated charcoal to prevent the absorption of chloroquine was
      investigated in healthy volunteers, and the effect of the charcoal-chloroquine
      ratio on the completeness of binding was studied in vitro. 2. After an overnight
      fast, six subjects ingested 500 mg of chloroquine phosphate with water, and
      another group of six subjects ingested 25 g of charcoal suspension within 5 min
      of chloroquine intake. The concentrations of chloroquine in plasma and whole
      blood were measured by high-performance liquid chromatography for 192 h. 3.
      Activated charcoal reduced the areas under the plasma and whole blood chloroquine
      concentration-time curves (AUC) from 0 to 192 h, the total AUCs, and the peak
      concentrations by 99% (P less than 0.001). 4. Chloroquine was very effectively
      bound by activated charcoal in vitro, even at low charcoal-chloroquine ratios.
      For example, at a ratio of 5:1, about 98% of chloroquine was bound. 5. Activated
      charcoal should be very effective in reducing the absorption of that fraction of
      chloroquine dose which is in the stomach at the time of charcoal administration.
      Because the acute toxicity of chloroquine is extremely high and death usually
      occurs within 1-3 h of overdosage, charcoal should be given as early as possible
      in suspected chloroquine intoxication.

PMID- 1349218
TI  - Studies on the disposition and metabolism of hydrazine in rats in vivo.
AB  - 1. Rats were given various doses of hydrazine orally and their plasma and liver
      hydrazine levels were determined (at various times up to 270 min after dosing) by
      gas chromatography/mass spectrometry. 2. The increase in the peak plasma level
      and in the area under the plasma concentration-time curve (AUC) were not directly
      proportional to the dose. 3. The ratio of plasma to liver hydrazine varied with
      dose suggesting saturation of an uptake mechanism might be occurring. 4. In a
      separate experiment hydrazine was still detectable in the plasma and liver 24 h
      after dosing with hydrazine i.p. 5. Rats were given the same doses of hydrazine
      and urine was collected for 24 h after dosing and assayed for hydrazine and
      acetylhydrazine. The proportion of hydrazine and acetylhydrazine excreted
      declined with dose. 6. Liver samples were taken for histopathological examination
      96 h after dosing. Only after the highest dose (81 mg kg-1) was there evidence of
      fatty liver, 96 h after a single dose, and a reduction in both liver and body
      weight.

PMID- 1349219
TI  - High-dose cyclophosphamide and dexamethasone in paraquat poisoning: a prospective
      study.
AB  - Between March 1986 and March 1988, 47 consecutive patients, whose paraquat
      intoxication was confirmed by urine testing, were enrolled in a prospective study
      on the treatment of paraquat poisoning. Fourteen received a standard treatment
      regimen consisting of fluid replacement and oral absorbents, and 33 received high
      dose cyclophosphamide and dexamethasone, in addition to standard therapy. The
      case fatality rate in both treatment groups (63 and 61%) was similar. In
      addition, all 26 patients whose paraquat serum concentrations were measured and
      who had a probability of survival of less than 65% according the survival curve
      of Hart et al. died, regardless of therapy. These included four in the
      cyclophosphamide/dexamethasone group and two in the standard treatment group who
      had prior survival probabilities between 50 and 65%. This indicated that the cut
      off curve relating mortality and paraquat serum concentrations was similar in
      both treatment groups. High-dose cyclophosphamide/dexamethasone treatment is
      unlikely to improve the prognosis of paraquat poisoning.

PMID- 1349220
TI  - Clinical features and treatment of Elapidae bites: report of three cases.
AB  - This report describes two accidents, involving snakes of the Micrurus corallinus
      species, where compromising respiratory function was not observed and the
      specific anti-elapidic serum was the single therapy used, and a third incident,
      probably involving Micrurus frontalis, where neostigmine was used to remedy
      respiratory failure.

PMID- 1349221
TI  - Analysis of the immunotoxic effects of xenobiotics.
AB  - 1. Current problems in immunotoxicology are reviewed with special attention to
      the sensitivity of the immune system to the effects of xenobiotics. 2.
      Sensitivity of target cells, route of exposure, dosage, mechanism of action and
      response of the immune system are discussed as the main factors responsible for
      the ultimate effects of drugs and chemicals. 3. The methodology of
      immunotoxicology is divided into two main steps: preclinical screening and the
      monitoring of exposed persons. 4. Conclusions are prescribed about future tasks
      in human immunotoxicology.

PMID- 1349222
TI  - The immunotoxicity of tributyltin oxide (TBTO) does not increase the
      susceptibility of rats to experimental respiratory infection.
AB  - 1. The dietary exposure of rats to tributyltin oxide at a concentration of 150
      ppm for 6 weeks is known to lead to a significant reduction in relative thymic
      weight. 2. To determine whether this reduction in thymic weight also leads to an
      impairment of function sufficient to alter the host response to micro-organisms,
      we have examined the development of virus- and mycoplasma-induced pneumonia in
      TBTO-exposed rats. 3. Using a quantitative histopathological method for measuring
      both the extent and duration of lung lesions in TBTO-exposed rats, no
      statistically significant increase in the extent or persistence of virus-induced
      lung lesions was found in rats exposed chronically to TBTO. 4. The susceptibility
      of rats to Mycoplasma pulmonis infection, alone, or in conjunction with viral
      pneumonia, was also not increased by dietary exposure to TBTO.

PMID- 1349223
TI  - Induction of DNA strand breaks in peripheral lymphocytes by soluble chromium
      compounds.
AB  - 1. Incubation of human lymphocytes with sodium dichromate (CrVI) at 37 degrees C
      for 3 h resulted in a dose-dependent increase in DNA strand breaks without
      concurrent cytotoxicity. In contrast, chromium acetate hydroxide (CrIII) failed
      to induce DNA strand breaks at sub-cytotoxic concentrations. 2. DNA strand breaks
      were also detected in the peripheral lymphocytes of Wistar rats, 24 h after
      intratracheal instillation of sodium dichromate (1.3 and 2.5 mg kg-1).
      Instillation of chromium acetate hydroxide (up to 21.8 mg kg-1) failed to induce
      DNA strand breaks in peripheral lymphocytes. In accord with previous studies,
      hexavalent chromium was found to be more readily absorbed from the lungs into the
      peripheral blood than chromium in its trivalent form. 3. The results of this
      study indicate that fluorometric analysis of DNA unwinding (FADU) in peripheral
      lymphocytes might be a convenient method of measuring an important biological
      effect of chromium in occupationally-exposed workers.

PMID- 1349224
TI  - Effects of joint exposures to selected peroxisome proliferators on hepatic acyl
      CoA oxidase activity in male B6C3F1 mice.
AB  - The interaction potential of peroxisome proliferators of similar and dissimilar
      structure was examined in B6C3F1 mice. Mice were fed diets containing varying
      concentrations of ciprofibrate (Cipro), clofibrate (Clof) or di(2
      ethylhexyl)phthalate (DEHP), or combinations of Cipro and Clof or Cipro and DEHP
      for 4 d. Induction of peroxisomal beta-oxidation, measured by increased acyl-CoA
      oxidase activity, was used as the endpoint for analysis. An additive response
      occurred following joint exposure to the structurally related compounds Cipro and
      Clof, whereas a possible synergistic response occurred at low dose combinations
      of the structurally dissimilar Cipro and DEHP. These findings represent the first
      report assessing the in-vivo interaction potential of structurally similar and
      dissimilar peroxisome proliferators and provides insight into the dose-response
      nature of joint exposures to certain non-genotoxic carcinogens.

PMID- 1349225
TI  - Effect of lead on the blood serum, liver and brain sialoglycoconjugate levels in
      rats.
AB  - Rats were exposed to an acute dose of lead (Pb) to study the effect of Pb
      intoxication on different sialoglycoconjugates in serum, brain and liver. Serum
      levels of total sialic acid (TSA), perchloric acid (PCA)-soluble sialic acid
      (PSA), lipid-bound sialic acid (LBSA), free sialic acid (FSA) and alpha 1-acid
      glycoprotein (alpha 1-AG) were determined. They were also estimated in brain and
      liver tissues, except for LBSA and FSA. All these constituents were found to be
      significantly raised in the serum but not in the brain. In the case of the liver,
      only alpha 1-AG levels were found to be increased significantly, the rest were
      not altered. The levels of these sialoglycoconjugates in serum might be useful as
      biomarkers of heavy metal toxicity.

PMID- 1349226
TI  - Cardiac toxicity following short-term exposure to methomyl in spraymen and
      rabbits.
AB  - A health surveillance study in 22 healthy spraymen showed significant T-wave
      changes (including inversion) in most of the limb leads and chest leads following
      5 d exposure to methomyl, a carbamate pesticide. Significant changes in plasma
      cholinesterase and lactic dehydrogenase activities were also noticed. The ECG
      changes could be reproduced in rabbits and were dose dependent. This type of ECG
      change following exposure to a carbamate compound is reported for the first time
      in occupationally-exposed subjects. The study results indicate that these changes
      are probably directly related to methomyl rather than its toxicity through
      cholinesterase inhibition. The significance of these changes remain to be
      investigated.

PMID- 1349227
TI  - Cigarette smoke inhibits cytosolic but not microsomal epoxide hydrolase of human
      lung.
AB  - The effect of cigarette smoke exposure on the activity of cytosolic and
      microsomal epoxide hydrolase (EH) has been investigated in human lung. Patients
      were classified as 'recent smokers' (n = 9) or 'non-recent smokers' (n = 10)
      according to whether they were or were not still smoking 1 month before surgery.
      Cytosolic EH was measured with [3H]trans-stilbene oxide as a substrate, whereas
      microsomal EH was measured with [7-3H]styrene oxide as a substrate. Microsomal EH
      activity did not differ between recent smokers (2.51 +/- 0.93 nmol min-1 mg-1)
      and non-recent smokers (2.74 +/- 1.10 nmol min-1 mg-1), whereas cytosolic EH
      activity was significantly lower in recent smokers (6.46 +/- 1.79 pmol min-1 mg
      1) than in non-recent smokers (8.41 +/- 2.09 pmol min-1 mg-1, P less than 0.05).
      Cytosolic EH activity was correlated with the number of days that had passed
      since the cessation of smoking (r = 0.58, P less than 0.05) and the effect was
      dose-dependent, since the enzyme activity was inversely correlated with the
      number of cigarettes smoked per day (r = 0.85, P less than 0.01). This suggests
      that recent smoking exposure inhibits the activity of cytosolic EH but not
      microsomal EH, and that the inhibition increases with the number of cigarettes
      smoked per day. The contribution of cytosolic enzymes to xenobiotic metabolism
      may be remarkable in extrahepatic tissues. The inhibition of cytosolic EH by
      tobacco smoke may reduce the inactivation of carcinogenic epoxides in human lung
      tissues and so may increase a person's susceptibility to lung cancer.

PMID- 1349228
TI  - Macaque CD4+ T-cell subsets: influence of activation on infection by simian
      immunodeficiency viruses (SIV).
AB  - Simian immunodeficiency virus (SIV) infects a small number of CD4+ T cells
      including "memory" T cells. The following describes the cell surface markers
      which may delineate subsets of CD4+ memory T cells and reviews how memory CD4+ T
      cells are activated and regulated through the T-cell receptor and such accessory
      receptors as CD28. The factors which may influence initial expression and
      infection of T cells by CD4 are discussed. Unlike activated and infected T cells,
      unstimulated CD4+ T cells have little or no SIV DNA detectable in the genomic
      fraction, but key activation signals may promote integration of viral DNA in
      memory T cells. Bacterial superantigens (SuperAg) can promote increased levels of
      SIV viral DNA in mature and immature T cells. Immunodeficiency virus products
      such as gp120, Nef, and Tat can affect CD4+ T-cell function. Whereas Nef can
      reduce expression of CD4, Tat reduces the expression of CD28. We hypothesize that
      the lack of expression of key accessory molecules on CD4 lineage T cells infected
      with immunodeficiency viruses may make infected T cells more susceptible to
      recall-antigen-induced programmed cell death.

PMID- 1349229
TI  - Inhibition of Ca(2+)-induced calcitonin secretion by somatostatin: roles of
      voltage dependent Ca2+ channels and G-proteins.
AB  - Somatostatin has recently been applied therapeutically for hypercalcitonemia in
      patients with calcitonin-producing tumours. Using calcitonin-secreting cells (C
      cells) of the medullary thyroid carcinoma cell line rMTC 44-2, we investigated
      the inhibitory action of somatostatin on calcitonin release, cytosolic Ca2+ and
      Ca2+ channel currents. The Ca(2+)-induced rises of the cytosolic Ca2+ and
      calcitonin secretion were greatly inhibited by somatostatin or its stable
      analogue octreotide. The effects of somatostatin were pertussis toxin-sensitive.
      Under voltage clamp conditions, C-cells exhibited slowly inactivating Ca2+
      channel currents. Bath application of 100 nM somatostatin reversibly reduced the
      Ca2+ channel current by about 30%. The Ca2+ channel current and its inhibition by
      somatostatin were not affected by intracellularly applied cyclic AMP. Moreover,
      pretreating the cells with pertussis toxin had no effect on the control Ca2+
      channel currents but greatly abolished its inhibition by somatostatin. The data
      show that somatostatin suppresses the Ca(2+)-stimulated calcitonin secretion by
      inhibiting voltage-dependent Ca2+ channel currents and by lowering cytosolic
      Ca2+. These actions of somatostatin involve pertussis toxin-sensitive G-proteins
      and occur independently of changes in the cyclic AMP concentration.

PMID- 1349230
TI  - Haemorrhagic fever with renal syndrome: clinical aspects.
AB  - Based on clinical and pathological features a typical case of haemorrhagic fever
      with renal syndrome passes through five phases: (1) febrile phase, (2)
      hypotensive phase, (3) oliguric phase, (4) diuretic phase and (5) convalescent
      phase. The major manifestations are fever, pain in the back and abdomen, flushed
      face, prostration, proteinuria, purpura and haemorrhage and acute renal failure.
      Selective right auricular haemorrhage, marked congestion and haemorrhage in the
      renal medulla and necrosis of the anterior lobe of the pituitary gland are the
      three prominent pathological findings. The clinical severity depends upon the
      causative agents, namely Hantaan virus, Seoul virus and the European form in that
      order. Specific serological diagnosis of haemorrhagic fever with renal syndrome
      is made by demonstrating a rise in titre of specific immunofluorescent antibody
      against Hantaan and related viruses. The management is supportive, based on an
      understanding of the pathophysiology of the disease.

PMID- 1349231
TI  - Haemorrhagic fever with renal syndrome, virological and epidemiological aspects.
AB  - Haemorrhagic fever with renal syndrome (HFRS) is characterized by fever,
      headache, abdominal pain, renal dysfunction and various haemorrhagic
      manifestations. The viruses causing HFRS all belong to the Hantavirus genus in
      the Bunyaviridae family. At least three of the different hantaviruses are
      associated with human disease: Hantaan, Seoul, and Puumala viruses. HFRS is
      endemic in a belt from Norway in the west, through Sweden, Finland, the Soviet
      Union, China, Korea to Japan in the east. The clinical severity of HFRS varies
      throughout this belt. A severe form with haemorrhagic manifestations and
      significant lethality (Korean haemorrhagic fever--caused by Hantaan and Seoul
      virus) occurs in Asia, while a milder form (nephropathia epidemica caused by
      Puumala virus) with less haemorrhagic manifestations and no or low lethality is
      found in Europe. All hantaviruses are spread by rodents where the major route of
      transmission to man is via aerosol from rodent urine, saliva and faeces. Although
      HFRS occurs with the same clinical picture in children as in adults both
      incidence rates and antibody prevalence rates are very low in children under 10
      years. Men of working age make up the bulk of clinical cases.

PMID- 1349232
TI  - Compartmentalization of the cellular immune response to the recombinant 65 kDa
      protein of Mycobacterium bovis BCG in patients with tuberculous pleuritis.
AB  - The recombinant 65 kDa mycobacterial protein of M. bovis BCG has been shown to be
      immunodominant in mice immunized with M. tuberculosis. Little is known about
      reactivity to this antigen in patients with tuberculous pleuritis. In this study
      therefore, pleural effusion and autologous peripheral blood lymphocytes obtained
      from patients with tuberculous and nontuberculous pleuritis were stimulated in
      vitro with the recombinant 65 kDa antigen. Proliferation was assessed by 3[H]
      thymidine incorporation. In addition, pleural effusion lymphocytes were activated
      in vitro with the 65 kDa antigen and tested for cytotoxic activity in 15-hr
      chromium-release assays. Pleural effusion lymphocytes obtained from a high
      percentage (56%) of patients with tuberculous pleuritis showed significant
      proliferative responses to the 65 kDa antigen, while the response in autologous
      peripheral blood lymphocytes was significantly lower. By contrast, pleural
      effusion lymphocytes obtained from patients with nontuberculous effusions were
      not reactive to the 65 kDa antigen. In addition, 65 kDa stimulated pleural
      effusion lymphocytes obtained from patients with tuberculous effusions showed
      antigen-specific lysis of autologous targets pulsed with the 65 kDa antigen.
      These results indicate compartmentalization of the immune response to the 65 kDa
      antigen and, in addition, provide evidence for in vivo involvement of this
      antigen in the immune response to M. tuberculosis.

PMID- 1349233
TI  - Induction of myelo-monocytic My7 antigen (CD13) expression by interferon-alpha in
      basal cells of cutaneous T-cell lymphomas.
AB  - The My7 antigen that is expressed on the basal cells in normal skin and
      inflammatory disorders is absent in the lesions of cutaneous T-cell lymphoma
      (CTCL). Induction of My7 expression in basal cells in the cutaneous lesions of 12
      patients with mycosis fungoides and three with Sezary syndrome treated with
      interferon-alpha 2a (IFN-alpha 2a) for 10 months was investigated. Biopsies were
      taken from the same area before treatment and after 2, 6 and 10 months of therapy
      with IFN-alpha 2a. My7 antigen was expressed on the basal cells only in those
      patients who showed either a complete or partial response to therapy with IFN
      alpha 2a.

PMID- 1349234
TI  - Eosinophilic pustular folliculitis in an HIV-positive man: response to
      cetirizine.
AB  - Eosinophilic pustular folliculitis is a rare condition which is being
      increasingly reported in HIV-positive patients. Many therapies have been used to
      treat this condition. We report the first successful use of the H1 antihistamine
      cetirizine to treat the condition and postulate that the specific
      antieosinophilic action of this drug may explain the beneficial clinical effect
      seen in our patient.

PMID- 1349235
TI  - Immunohistochemical localization of dipeptidyl aminopeptidase IV in thyroid
      papillary carcinoma.
AB  - The localization of dipeptidyl aminopeptidase IV expressed aberrantly in thyroid
      carcinoma was studied by immunoelectron microscopy using a monoclonal antibody to
      the enzyme with special reference to enzyme-histochemical staining of the enzyme.
      Five thyroid papillary carcinomas were investigated including two lymph-node
      metastases. All cases showed the dense immunoreaction product on the apical
      membrane and only traces of the product on lateral membranes, endoplasmic
      reticulum and nuclear membranes. In one case only, the dense product was observed
      on basal tubular structures. Analysis, using immunogold labelling on pre-embedded
      cryosections, revealed that dipeptidyl aminopeptidase IV was localized on the
      luminal surface of cancer cells. Two different distribution patterns of
      dipeptidyl aminopeptidase IV activity staining, diffuse and apical patterns,
      reported previously were thought to be due to different amounts of dipeptidyl
      aminopeptidase IV in the cytoplasm of cancer cells. This enzyme-histochemical
      staining method is useful for pathological diagnosis of thyroid tumours and can
      be applied to clinical materials. The enzyme localization is revealed by the
      staining pattern.

PMID- 1349236
TI  - Takayasu arteritis.
AB  - Takayasu Arteritis is a vasculitis of the giant cell type which affects young
      people. Complications of this disease can include myocardial infarction, stroke,
      limb loss, renal failure, and mesenteric ischemia. A case study demonstrates some
      of the complexities of diagnosis and treatment for this condition. Nursing care
      should be directed toward the alteration in tissue perfusion, prevention of
      infection in a patient on immunosuppressive therapy, and a variety of potential
      problems with coping.

PMID- 1349237
TI  - Annual general meeting of the British Society for Haemostasis and Thrombosis.
      Nottingham, 19-20 March 1992. Abstracts.

PMID- 1349238
TI  - Joint meeting of the British Society for Haemostasis and Thrombosis and the Royal
      Society of Medicine Forum on Lipids. London, 18-19 September 1991. Abstracts.

PMID- 1349239
TI  - Retinoic acid induces changes in the localization of homeobox proteins in the
      antero-posterior axis of Xenopus laevis embryos.
AB  - We have studied the localization of the proteins of Xeb1 and Xeb2, two homeobox
      (hbx)-containing genes that are expressed during the early development of Xenopus
      laevis. Both proteins are expressed in juxtaposed and partially overlapping
      domains along the antero-posterior axis of Xenopus laevis embryos, with clearly
      defined anterior boundaries. Xeb2 is predominantly expressed in the caudal region
      of the hindbrain, whereas the Xeb1 protein is located in the most rostral region
      of the spinal cord. Furthermore, both proteins are expressed in single cells
      dispersed in the lateral flanks of the embryo in positions that correlate with
      the expression domains in the neural tube. We suggest that these cells are
      migratory neural crest cells that have acquired positional information in the
      neural tube prior to migration. The Xeb2 protein was also detected in the most
      posterior branchial arches and the pronephros. In stage 45 embryos, nuclei of the
      IX-X cranial ganglia, the lung buds and cells spreading into the forelimb
      rudiment express the Xeb2 antigen. The Xeb1 protein was also detected in the lung
      buds and the forelimb rudiment. To examine the effect of retinoic acid on
      expression, gastrula embryos were treated with all-trans retinoic acid (RA).
      Increasing concentrations of RA caused progressive truncation of anterior
      structures. The most severely affected embryos lacked eyes, nasal pits,
      forebrain, midbrain and otic vesicles, and the anterior boundary of the hindbrain
      seemed to be displaced rostrally. This alteration correlates with a progressive
      displacement of the anterior boundary of the expression domain of Xeb2. On the
      other hand, 10(-6) M RA induces an ectopic site of Xeb1 expression at the
      anterior end of the central nervous system, located just anterior to the extended
      domain of Xeb2 whereas expression in the spinal cord remains unaffected.

PMID- 1349240
TI  - Changes in brain gene expression in schizophrenic and depressed patients.
AB  - Poly(A+) mRNA was extracted from the post-mortem brain of schizophrenics (9
      subjects), unipolar depressives (5 subjects) and controls (10 subjects) and used
      to direct the in vitro translation of radiolabelled protein in a cell-free
      reticulocyte-lysate system. Protein species were analysed on two-dimensional
      gels. Over 200 products were detected and, from these, 74 well-resolved species
      were chosen for further analysis. The optical density of each product was
      quantified by image analysis and normalised with respect to overall gel
      intensity. It was found that 7 novel, uncharacterised protein species, ranging
      from molecular weights (Mr) 17 kDa to 38 kDa and apparent isoelectric points (pI)
      5.7-7.1, changed significantly in intensity in the psychotic groups compared to
      controls. One species changed only in the schizophrenia group (Mr = 26 kDa, pI =
      5.8, 18% of control intensity) and 3 changed only in the depressive group (Mr =
      38 kDa, pI = 6.2, 540% of control; Mr = 34 kDa, pI = 6.2, 6% of control; Mr = 17
      kDa, pI = 5.7, 238% of control). Three further protein species were common to
      both psychotic groups (one species decreased in both schizophrenia and
      depression, Mr = 33 kDa, pI = 5.8; two species showed opposing intensity changes,
      decreasing in schizophrenia and increasing in depression, Mr = 35 kDa, pI = 7.1;
      Mr = 23 kDa, pI = 6.1). None of these changes was a function of post-mortem delay
      or mode of death. It is quite likely that such protein species reflect the
      abundance of specific mRNAs and target gene systems associated with the disease
      state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349241
TI  - A quantitative analysis of saccades and smooth pursuit during visual pursuit
      tracking. A comparison of schizophrenics with normals and substance abusing
      controls.
AB  - The eye movements of schizophrenic patients are characterized by decreased smooth
      pursuit gain and an increased frequency of saccades. However, the nature of these
      saccades and their function during smooth pursuit has not been clearly defined.
      To address this issue we examined the eye movements of 22 schizophrenic patients,
      20 substance abusing patients (primarily alcohol; some with concomitant cocaine
      and/or cannabis abuse), and 17 normal controls during a visual pursuit task using
      infra-red oculography. A computerized pattern recognition algorithm divided
      pursuit eye movements into two basic components: smooth pursuit and saccadic eye
      movements. The algorithm also determined eye position error and velocity error
      before and after each saccade. Schizophrenic patients had lower smooth pursuit
      gain (p less than 0.02) and made more saccades during smooth pursuit (p less than
      0.02) than either comparison group. When saccades were assigned to subcategories
      based on direction and position error, only the frequency of 'catch-up' saccades
      differentiated schizophrenic patients from the comparison groups (p less than
      0.05). Smooth pursuit gain was negatively correlated with saccadic frequency
      among all three subject groups. Eye velocity preceding saccades was significantly
      lower among the schizophrenic patients, but pre or post saccadic position error
      did not differ among the three groups. Discrete analysis of the fine structure of
      visual pursuit tracking may lead to a better understanding of eye movement
      abnormalities in schizophrenia.

PMID- 1349242
TI  - First International Conference on the Pathogenesis of Mycobacterial Infections: a
      summary.
AB  - Two hundred scientists representing 25 countries assembled for the First
      International Conference on the Pathogenesis of Mycobacterial Infections, which
      was held in Stockholm on 27-29 June 1990. A total of 40 speeches and 80 poster
      presentations covered nearly all of the recent progress made in the field of
      mycobacterial pathogenicity. The present report is intended as a brief summary of
      the research results presented during the conference and focuses on findings of
      broad scientific interest. However, the omission of other presented findings from
      this report does not constitute any judgment of their scientific quality.

PMID- 1349243
TI  - 2nd International Symposium on Endothelium-Derived Vasoactive Factors. Basel,
      Switzerland, April 22-25, 1992. Abstracts.

PMID- 1349244
TI  - False-positive flow cytometric platelet glycoprotein IIb/IIIa expression in
      myeloid leukemias secondary to platelet adherence to blasts.
AB  - Because neither morphologic nor routine cytochemical features are pathognomonic,
      the diagnosis of acute megakaryoblastic leukemia (AML-M7) is difficult, requiring
      either specialized ultrastructural or immunologic techniques. Because the
      ultrastructural techniques are cumbersome, immunologic assays for expression of
      several platelet-specific antigens, such as CD41a (platelet glycoprotein
      IIb/IIIa), have become the primary method used to detect megakaryoblastic
      differentiation. In our flow cytometric analysis of the immunophenotypes of over
      1,000 cases of AML from patients registered to Southwest Oncology Group (SWOG)
      Treatment Protocols, we found that 38% of cases demonstrated CD41a reactivity.
      Because this frequency of CD41a expression by flow cytometry greatly exceeded the
      number of morphologically defined cases of AML-M7, we postulated that the
      reaction may be caused by platelets adherent to leukemic blasts. To investigate
      this hypothesis, we performed a side-by-side comparison of flow cytometric and
      cytospin immunofluorescence studies on 37 cases of adult de novo AML that
      demonstrated a wide range of CD41a expression by flow cytometric analyses. We
      found that the expression of CD41a detected by flow cytometric techniques was
      secondary to adherent platelets or platelet fragments in 85% of cases. Many of
      these cases also expressed the lineage-specific carbohydrate, LNF III (CD15),
      which may mediate platelet adhesion to mature monocytes and neutrophils. Only 15%
      of the CD41a flow cytometrically positive cases demonstrated true diffuse
      membrane and cytoplasmic positivity on cytospin slides indicative of
      megakaryoblastic differentiation. Cytospin immunofluorescence for CD41a should be
      performed on all cases of suspected AML-M7. If only flow cytometric techniques
      are used, adherent platelets may result in the erroneous diagnosis of this AML
      subtype.

PMID- 1349245
TI  - Selecting dose-intense drug combinations: metastatic breast cancer.
AB  - A mathematical model previously described is applied to the problem of selecting
      drug combinations for metastatic breast cancer. The model accounts for the
      differing single-agent activities of the drugs as well as their differing
      profiles of toxicity. With no bone marrow protection, combinations with cisplatin
      offer a small improvement in total equivalent dose over therapy with the more
      active single-agents. Restricting consideration to the four most commonly used
      agents, single-agent doxorubicin has the greatest equivalent dose. With
      protection for leukopenia or willingness to accept a higher incidence of severe
      leukopenia, a combination with large doses of cyclophosphamide, doxorubicin, and
      fluorouracil, and a small dose of cisplatin has greatest equivalent dose. The
      doublets cyclophosphamide/fluorouracil or fluorouracil/cisplatin at higher doses
      are almost as good. With protection for leukopenia and thrombocytopenia, a
      cyclophosphamide/thiotepa combination at very high doses maximizes total
      equivalent dose. This approach can be used to identify regimens worthy of
      prospective evaluation.

PMID- 1349246
TI  - Education and training in gastroenterology.

PMID- 1349247
TI  - Drug treatment for acute upper gastrointestinal bleeding.

PMID- 1349248
TI  - Analysis of late graft failure after allogeneic bone marrow transplantation:
      detection of residual host cells using amplification of variable number of tandem
      repeats loci.
AB  - In an attempt to gain insight into the etiology of late graft failure, we
      analysed the origin of bone marrow mononuclear cells (BMMC) and peripheral blood
      leukocytes in patients with this syndrome by taking advantage of DNA fragment
      length polymorphisms in variable number of tandem repeats (VNTR) loci.
      Amplification of the VNTR loci in DNA from BMMC using the polymerase chain
      reaction revealed the persistence of host cells in two of four patients studied.
      One of the patients, whose cultured lymphocytes inhibited in vitro growth of
      donor-derived hemopoietic progenitor cells, responded to immunosuppressive
      therapy and donor-derived hemopoiesis was restored. In the other patient, host
      derived polymorphonuclear leukocytes (PMN) appeared together with donor-derived
      PMN from the early post-transplant period, and he proceeded to relapse with
      myelodysplastic syndrome. In the other two patients in whom host cells were not
      detectable, the marrow hypoplasia was associated with chronic graft-versus-host
      disease (GVHD). The hypoplasia improved significantly as the chronic GVHD
      improved in response to immunosuppressive therapy. We conclude that detecting
      minimal residual host cells by means of amplification of VNTR loci is valuable
      for understanding the etiology of late graft failure in marrow transplant
      recipients, and could prove helpful for choosing appropriate therapy for this
      syndrome.

PMID- 1349249
TI  - Prolonged remission of accelerated phase Philadelphia chromosome negative chronic
      myeloid leukemia following autologous recovery of normal hematopoietic elements
      after busulfan/cyclophosphamide and allogeneic marrow transplantation.
AB  - We describe here a patient with accelerated phase Philadelphia chromosome (Ph1)
      negative chronic myelogenous leukemia without BCR gene rearrangement, who
      received an allogeneic bone marrow transplant following a conditioning regimen
      consisting of busulfan (BU) and cyclophosphamide (CY). Hematopoiesis was restored
      following splenectomy performed 1 month post-transplant. There were no
      distinguishing cytogenetic differences between donor and host. Five years post
      transplant the patient relapsed with the original disease. Restriction fragment
      length polymorphism (RFLP) studies performed at that time exhibited host specific
      DNA markers suggesting recurrent leukemia of host origin. RFLP analysis of the
      cells cryopreserved immediately post-transplant also revealed all cells to be of
      host origin. This patient experienced 5 years of remission with autologous
      hematopoietic recovery from an aggressive myeloproliferative disorder after high
      dose BU and CY without engraftment of donor hematopoietic cells.

PMID- 1349250
TI  - Is the concept of frontal-subcortical dementia relevant to schizophrenia?
AB  - A syndrome of subcortical dementia has been described in conditions predominantly
      affecting the basal ganglia or thalamus, structures that have also been
      implicated in the pathogenesis of schizophrenia. There are similarities between
      subcortical dementia and the type II syndrome of schizophrenia, in terms of
      clinical features, pattern of neuropsychological deficits, pathology,
      biochemistry and data from brain-imaging studies. These similarities raise the
      possibility that certain schizophrenic symptoms, particularly negative symptoms
      and disturbance of movement, may reflect subcortical pathology.
      Neuropsychological deficits of presumed frontal lobe origin have been reported in
      some schizophrenic subjects. The occurrence of such deficits in a condition in
      which frontal lobe pathology has not been clearly demonstrated may be explicable
      in terms of a subcortical deafferentation of the pre-frontal cortex.

PMID- 1349251
TI  - Role of general practitioners in the care of long-term mentally ill patients.

PMID- 1349252
TI  - A species-specific population of tyrosine hydroxylase-immunoreactive neurons in
      the medial amygdaloid nucleus of the Syrian hamster.
AB  - The medial amygdaloid nucleus (Me) is part of a neural pathway that regulates
      sexual behavior in the male Syrian hamster. To characterize the neurochemical
      content of neurons in this nucleus, brains from colchicine-treated adult male and
      female hamsters were immunocytochemically labeled using antibodies that recognize
      the catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH), dopamine-beta
      hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT), as well as
      dopamine. A large population of TH-immunoreactive (TH-IR) neurons was observed
      throughout Me of male and female hamsters, primarily concentrated in the
      midrostral and caudal portions of the nucleus. The somata were generally small to
      medium in size and bipolar. Brains from animals that did not receive colchicine
      contained a limited number of TH-IR neurons in Me as reported previously. The DBH
      and PNMT antisera did not label any cells in Me of colchicine-treated animals,
      and the dopamine antiserum labeled neurons in the same location as the caudal
      group of TH-IR cells. Therefore, these caudal TH-IR neurons are interpreted to be
      dopaminergic. The rostral group of TH-IR neurons, on the other hand, may be
      producing only the immediate precursor of dopamine, L-3,4-dihydroxyphenylalanine
      (L-DOPA). The TH-synthesizing neurons in Me of the Syrian hamster appear to be a
      species-specific group of cells located outside of the previously described
      catecholaminergic cell groups.

PMID- 1349253
TI  - Selective potentiation of NMDA-induced activity and release of excitatory amino
      acids by dynorphin: possible roles in paralysis and neurotoxicity.
AB  - Selective antagonists of N-methyl-D-aspartate (NMDA) excitatory amino acid (EAA)
      receptors have been shown to protect against dynorphin-A (DYN)-induced paralysis
      and neurotoxicity in the spinal cord. To test the hypothesis that either DYN
      induced paralysis or neurotoxicity involves an enhanced release of EAAs, we used
      microdialysis to monitor aspartate (Asp) and glutamate (Glu) release in both the
      lumbar spinal cord extracellular fluid (ECF) and the spinal cord cerebral spinal
      fluid (CSF) of conscious rats in response to DYN (1-13). Injection of 5 nmol of
      DYN produced temporary paralysis in 8 of 10 animals, but did not significantly
      change Asp or Glu release in either the ECF or the CSF. Injection of 20 nmol of
      DYN caused permanent paralysis and neuronal cell loss in all animals tested as
      well as a significant increase of Asp and Glu in both the ECF and the CSF, and a
      decrease in glutamine (Gln) release only in the ECF. Pretreatment with 1 mg/kg of
      the NMDA antagonist MK-801 blocked both paralysis and amino acid changes in the
      ECF. Pretreatment of animals with 5 mg/kg naloxone inhibited glutamate release in
      the ECF, but did not block paralysis, Asp release or inhibition of Gln release.
      As MK-801 sensitive paralysis by DYN was not mediated through enhanced EAA
      release, we examined whether DYN could act through postsynaptic facilitation of
      NMDA receptors by testing the ability of DYN to alter the magnitude of a
      behavioral response produced by intrathecal injection of NMDA in mice.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1349254
TI  - Pharmacological specificity of the increase in neurotensin concentrations after
      antipsychotic drug treatment.
AB  - Neurotensin is an endogenous neuropeptide that produces many CNS effects that are
      similar to the behavioral and physiological alterations seen after administration
      of antipsychotic drugs to laboratory animals. As previously reported, sub-chronic
      (3 week) and acute (single injection) treatment with haloperidol (1 mg/kg), a
      clinically effective antipsychotic drug increases neurotensin concentrations in
      the nucleus accumbens and the caudate nucleus. In contrast, a tricyclic
      antidepressant (desipramine, 10 mg/kg), an anxiolytic (chlordiazepoxide, 25
      mg/kg) and a histamine H1 receptor antagonist (diphenhydramine, 20 mg/kg) did not
      alter neurotensin concentrations in these brain regions after sub-chronic or
      acute treatment. These data demonstrate pharmacologic specificity to the
      antipsychotic drug-induced increases in regional brain neurotensin
      concentrations, and support the hypothesis that these changes may contribute to
      the clinical efficacy of these drugs.

PMID- 1349255
TI  - An electron microscopic morphometric comparison of tyrosine hydroxylase
      immunoreactive innervation in the neostriatum and the nucleus accumbens core and
      shell.
AB  - The synaptic targets and size distributions of the sectioned profiles of tyrosine
      hydroxylase immunoreactive fibers and boutons in the neostriatum and shell and
      core of the nucleus accumbens were evaluated. Significantly more synaptic
      contacts where dendrite shafts are the postsynaptic element were observed in the
      shell than in the core of the nucleus accumbens or neostriatum. Relative to the
      core and neostriatum, a significantly greater proportion of the tyrosine
      hydroxylase immunoreactive innervation of the accumbal shell consisted of thin
      fiber and small bouton profiles. Thus, with regard to the morphometric parameters
      evaluated, the core of the nucleus accumbens is aligned with neostriatum and the
      shell is different from the core and neostriatum. In the light of these data, it
      is probably that the effects of the dopaminergic innervation in the core resemble
      the effects in neostriatum more than do those in the shell.

PMID- 1349257
TI  - The therapeutic potential of long-acting beta 2-adrenoceptor agonists in allergic
      inflammation.

PMID- 1349256
TI  - Basic fibroblast growth factor protects striatal neurons in vitro from NMDA
      receptor mediated excitotoxicity.
AB  - Basic fibroblast growth factor (bFGF) promotes the survival and outgrowth of
      neurons. In this study the neuroprotective effects of bFGF were examined in 12-18
      day-old cultured striatal neurons exposed to glutamic acid, kainic acid (KA), and
      quinolinic acid (QA), an N-methyl-D-aspartate (NMDA)-receptor agonist. Results
      showed that preincubation with bFGF (6 pM) from the day of plating significantly
      increased the survival of striatal neurons treated for 3 h with glutamate (3 mM)
      or QA (1 mM), but had little effect on KA (1 mM) induced toxicity. Moreover,
      maximum protection by bFGF against glutamate neurotoxicity was observed in
      cultures treated as little as 2 h before glutamate exposure. These results show
      that bFGF markedly protects striatal neurons from NMDA-receptor induced
      neurotoxicity.

PMID- 1349258
TI  - Inhibitory effects of formoterol and terbutaline on the development of late phase
      skin reactions.
AB  - The capacity of the beta 2-agonist terbutaline and the longer-acting beta 2
      agonist formoterol to suppress the development of late phase skin reactions to
      anti-human IgE was evaluated in 17 healthy volunteers. Anti-IgE injected
      intradermally per se induced an early weal and flare reaction, followed by a
      progressively increasing induration, the LCR, with a duration of greater than or
      equal to 24 hr. The LCR was inhibited by 40% when the weal was infiltrated with
      formoterol 250 ng 30 min after challenge (n = 9, P less than 0.01). The same anti
      LCR effect was achieved by compensating for the shorter duration of action of
      terbutaline with repeated drug infiltration in 12.5 micrograms doses of the weal
      produced by anti-IgE up to 3 1/2 hr after challenge (n = 8). The data support the
      hypothesis that beta 2-agonists, both short- and long-acting, inhibit IgE
      dependent LCRs by preferentially interacting with inflammatory events after the
      initial mast cell degranulation.

PMID- 1349260
TI  - [Takayasu's arteritis: a study by vascular sonography with special emphasis on
      carotid duplex].
AB  - Takayasu's arteritis (TA) is a chronic inflammatory disease mainly affecting
      young females involving the great vessels; the aorta and its major branches.
      Diagnosis and delineation of patterns of involvement used to depend on intra
      arterial angiography in the past. With the advent of high resolution duplex
      ultrasonographic technique, TA can be non-invasively inspected in the vasculitis
      phase. Based on our ultrasound study of cervical and lower extremity vessels, 6
      patients were proved to have TA by angiography. Some characteristic carotid
      imaging findings can be identified at the sonographic probe detectable regions,
      i.e., (1) The inflammatory changes of TA mainly involved the proximal parts of 3
      major cervical branches from the aortic arch, but the distal parts of them and
      the internal carotid arteries are relatively spared. (2) The inflammatory plaques
      of TA are relatively homogeneous in appearance, concentric in deposition and a
      long extent of involvement. Differential diagnosis between TA and atherosclerotic
      changes can be made by the preferential sites, echogenic properties, length of
      involvement and manner of proliferation. Regular follow-up by ultrasonography in
      2 patients showed that response to treatment and disease progression could be
      easily monitored.

PMID- 1349261
TI  - 3rd Canadian conference on neurodegenerative diseases. Proceedings of a
      symposium. L'Esterel, Quebec, April 4-6, 1991.

PMID- 1349259
TI  - The effect of azelastine on the early allergic response.
AB  - To study the effect of azelastine on the immediate reaction to nasal allergen
      challenge, we performed a double blind, placebo-controlled cross-over clinical
      trial. Thirteen subjects with seasonal allergic rhinitis underwent nasal
      challenge with antigen 4 hr after a single oral 2 mg dose of azelastine. The
      response was monitored by counting the number of sneezes and by measuring the
      levels of histamine, prostaglandin D2, immunoreactive sulphidopeptide
      leukotrienes, kinis and TAME-esterase activity in recovered nasal lavages. After
      a single dose of azelastine, there was a significant reduction in sneezing (10 vs
      2, P = 0.01) and in the median levels of recovered TAME-esterase activity (63.1
      vs 17.5 c.p.m. x 10(-3), P = 0.01), immunoreactive sulphidopeptide leukotrienes
      (7.5 vs 2.1 ng/ml, P = 0.03) and kinins (1370 vs 251 pg/ml, P = 0.03), with no
      significant reduction in the median levels of histamine (3.7 vs 1.2 ng/ml, P =
      0.2) and prostaglandin D2 (70 vs 70 pg/ml, P = 0.2) compared to placebo (numbers
      represent total increase over diluent challenge). These results suggest that
      azelastine does not inhibit mast cell activation but affects the consequences of
      released histamine, namely sneezing, increased vascular permeability and the
      generation of kinins. The results further suggest that other cells, in addition
      to mast cells, might be responsible for the generation of leukotrienes during the
      early allergic response, and that azelastine reduces their ability to generate
      this mediator or that inhibition of leukotriene release from mast cells occurs at
      lower drug concentrations.

PMID- 1349262
TI  - A rationale for dopamine agonists as primary therapy for Parkinson's disease.
AB  - Levodopa is the most potent symptomatic treatment for Parkinson's disease but
      adverse reactions are common and the initial response is not maintained. Further
      there is recent evidence that suggests that free radicals generated from the
      oxidative metabolism of dopamine may contribute to the pathogenesis of
      Parkinson's disease. This raises the possibility that levodopa therapy by way of
      its conversion to dopamine may promote free radical formation and accelerate the
      rate of neuronal damage. Levodopa sparing strategies designed to minimize the
      cumulative levodopa dosage employed over the course of the disease seem a
      rational way to treat Parkinson patients in face of current information. Such a
      strategy would include the use of dopamine agonists as primary symptomatic
      therapy, the introduction of levodopa as an adjunct when dopamine agonists can no
      longer sufficiently provide satisfactory clinical control and the use of the
      lowest dose of levodopa that will provide satisfactory clinical control. In this
      way symptomatic control is not compromised on theoretical grounds, but the
      cumulative levodopa dose is minimized in an effort to reduce the likelihood of
      free radical formation with their potential adverse consequences on disease
      progression.

PMID- 1349263
TI  - Synergistic interactions of D1- and D2-selective dopamine agonists in animal
      models for Parkinson's disease: sites of action and implications for the
      pathogenesis of dyskinesias.
AB  - The addition of a D2 agonist such as bromocriptine to L-Dopa therapy can often
      improve the response of patients with Parkinson's disease dramatically.
      Simultaneous activation of D1 and D2 dopamine receptors can produce a synergistic
      effect on locomotion in rats and primates. However, despite the importance of
      this addition of a D2 agonist to the D1/D2 agonist L-Dopa, little is known of the
      sites of action of these agents. Recent work suggests that, in addition to D1 and
      D2 dopamine receptor sites in the striatum (caudate-putamen), L-Dopa and D1
      agonists have important effects at D1 dopamine receptors in the substantia nigra.
      Animal experiments suggest that D1 and D2 dopamine receptor agonists probably
      also affect different outflow pathways from the striatum. An understanding of
      these pathways and how dopamine agonists affect them gives insight into some of
      the clinical problems experienced in treating Parkinson's disease (the "on-off"
      phenomenon, for example). D1/D2 dopamine receptors also differentially affect
      gene expression and regulation in the striatum. An understanding of the
      anatomical and biochemical location of the actions of dopamine receptor agonists
      will be important in maximizing the beneficial effects and minimizing the side
      effects of both presently-used drugs and new treatments.

PMID- 1349264
TI  - The place of the dopaminergic agonists in the treatment of Parkinson's disease:
      the view from the trenches.
AB  - The use of the dopamine receptor agonists in Parkinson's disease has a compelling
      logic. These agents are supposed to act independently of the dying cells of the
      substantia nigra directly on the cells of the striatum. Early clinical trials in
      advanced disease were only mildly impressive. Later they were found to be
      beneficial in early disease but their effectiveness waned. Their ultimate failure
      may reflect the fact that the majority of current agents do not stimulate D1 and
      D2 receptors in a physiologic ratio. The drugs may act presynaptically and with
      the eventual loss of the anatomic relationships between nigra and striatum the
      drugs fail. There is, however, a rationale to their current use. When used along
      with L-Dopa in early disease the development of late-stage fluctuations are
      reduced with the same anti-parkinsonian benefits. Merging this concept with the
      demonstrated effect of selegiline in slowing the course of the disease, the
      current practice of triple therapy with selegiline, L-Dopa and a dopamine
      receptor agonist emerges.

PMID- 1349265
TI  - Tyrosine aminotransferase: a transaminase among others?
AB  - Tyrosine aminotransferase (L-tyrosine: 2 oxoglutarate aminotransferase; EC
      2.6.1.5; TATase) is the first enzyme in the catabolic pathway of tyrosine. The
      gene of this transaminase is regulated by glucocorticoid hormones as well as via
      the cAMP pathway. This review gives a brief survey of the structural and physico
      chemical properties of this well-known protein. A comparative study of the
      properties of TATase with other aminotransferases is also included to analyse
      this molecule for itself, and not only as a marker used in studies on enzymatic
      induction. Finally, the regulation of the gene expression is presented, in order
      to underline a few important features of this model.

PMID- 1349266
TI  - Synaptic contacts of tyrosine hydroxylase-immunoreactive elements in the inner
      plexiform layer of the retina of Bufo marinus.
AB  - Tyrosine hydroxylase (TH) immunocytochemistry was utilized to quantify
      dopaminergic synapses in the inner plexiform layer of the retina of Bufo marinus.
      Since dopaminergic cells have bistratified dendritic arborisation in the inner
      plexiform layer, attention was given to the segregation of synapses between the
      scleral and the vitreal sublaminae. Light-microscopically, a more elaborate
      dendritic branching was observed in the scleral than in the vitreal sublamina. In
      contrast, about 55% of synapses occurred in the vitreal one fifth of the inner
      plexiform layer, 30% in the scleral fifth, and 15% in the intermediate laminae.
      Input sources and output targets showed only minor quantitative differences
      between sublaminae 1 and 5. TH-immunoreactive processes were found in presynaptic
      (62.8%) and postsynaptic (37.2%) positions. Synapses to the stained dendrites
      derived from bipolar (40.4%) and amacrine (59.6%) cells, whereas outputs from the
      TH-positive processes were directed to amacrine cells (56.8%) and to small and
      medium-sized dendrites (35.4%); at least some of these can be considered as
      ganglion cell dendrites. TH-positive profiles neither formed synapses with each
      other nor were presynaptic to bipolar cell terminals. Junctional appositions of
      the immunoreactive profiles were occasionally seen on non-stained amacrine and
      ganglion cell dendrites in the scleral sublamina of the inner plexiform layer and
      on optic axons in the optic fibre layer. Although dopaminergic cells are mainly
      involved in amacrine-amacrine interactions, inputs from bipolar terminals and
      outputs to ganglion cell dendrites were also substantial, suggestive of a role
      also in vertical information processing.

PMID- 1349267
TI  - The Vineberg procedure revisited: angiographic evaluation and coronary artery
      bypass surgery in a patient 21 years following bilateral internal mammary artery
      implantation.
AB  - A patient receiving bilateral internal mammary implantation (Vineberg's
      operation) in 1969 was symptom free for a period of 21 years. In 1990 he
      developed acute myocardial infarction followed by post-infarction angina. Cardiac
      catheterization revealed severe left main and three vessel disease and patency of
      both mammary implants which filled the left anterior descending and circumflex
      coronary arteries via collaterals. Coronary artery bypass surgery was indicated
      due to the native coronary artery disease and inability of the internal mammary
      grafts' blood flow to alleviate symptoms. The patient underwent direct coronary
      artery bypass grafting utilizing femoral vessels for cannulation and saphenous
      veins for grafting, while preserving the mammary implants. This unique case
      attests to the longevity of the internal mammary artery grafts. These grafts,
      even if directly implanted, can serve as a crucial source of blood to an
      otherwise severely underperfused myocardium. Strategy and technical aspects of
      surgical redo in patients who underwent Vineberg's operation are discussed.

PMID- 1349269
TI  - Basic fibroblast growth factor promotes transmitter storage and synthesis in
      cultured chromaffin cells.
AB  - We have studied the effects of basic fibroblast growth factor (bFGF), which
      occurs in the adrenal medulla, on the survival, morphological phenotype, storage
      capacity for catecholamines and induction of the synthesizing enzymes tyrosine
      hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) of cultured
      chromaffin cells from young postnatal rats. Basic FGF (40 ng/ml), like nerve
      growth factor (NGF; 40 ng/ml) prevented a drastic numerical decrease of
      chromaffin cells over a 4-day culture period, but, in contrast to NGF, did not
      induce neurite outgrowth, unless the cells were maintained for 7 days. Basic FGF
      was also more effective than NGF in maintaining the initial storage capacity for
      catecholamines, and even increased it under certain culture conditions (laminin
      instead of polyornithine, or 200 ng instead of 40 ng/ml). Basic FGF and NGF did
      not induce TH and PNMT activities beyond their initial levels, but partially
      prevented the reduction of TH activity seen after 4 days in culture. Based on the
      present data and the previously reported greater in vitro survival and
      transmitter stability of older chromaffin cells, which contain bFGF, and the
      relative instability of young postnatal chromaffin cells, which express no or
      very low levels of bFGF until 8 days postnatally, but respond to it, we
      hypothesize that bFGF is an important autocrine/paracrine maintenance factor for
      adult chromaffin cells.

PMID- 1349268
TI  - Mesencephalic dopaminergic cells exhibit increased density of neural cell
      adhesion molecule and polysialic acid during development.
AB  - In the developing mesencephalon of the rat, the dopaminergic neurons are
      generated in the ventricular zone of the basal plate between E11 and E15 and then
      migrate along radial glia to the ventral surface of the developing mesencephalon.
      To study the factors that control migration and maturation of the dopaminergic
      neurons, we immunolabeled embryo and pups, ages E12-P21, for neural cell adhesion
      molecule (NCAM), polysialic acid (PSA) - a polysaccharide found in high amounts
      on NCAM during development, tyrosine hydroxylase (TH) - a marker of mesencephalic
      dopaminergic cells, and vimentin - the major cytoskeletal protein in radial glia
      in the rat. At E13, we noted that cells throughout the mesencephalon contained
      NCAM-immunoreactive (NCAM-IR) material but that cells along the ventral surface
      of the mesencephalon contained an increased amount of NCAM-IR material and PSA
      immunoreactive (PSA-IR) material. At this age, we first noted a small number of
      TH-immunoreactive (TH-IR) cells adjacent to the marginal zone of the ventral
      surface of the mesencephalon. Many of the TH-IR cells contained an increased
      density of NCAM-IR material. At age E14, the pattern of increased density of NCAM
      IR material on cells along the ventral surface of the mesencephalon persisted and
      a conspicuous amount of PSA-IR material was also noted on cells in this region.
      TH-IR cells were more numerous, and a striking number of the TH-IR cells also
      contained an increased amount of NCAM-IR material and PSA-IR material. With
      increasing age the distribution of NCAM-IR material and PSA-IR material in the
      mesencephalon became more uniform. Our work suggests that NCAM may be involved in
      control of migration and synthesis of TH in the dopaminergic cells of the
      developing mesencephalon.

PMID- 1349270
TI  - Drug-transporter proteins in clinical multidrug resistance.
AB  - Upon exposure to chemotherapeutic drugs, mammalian cells can acquire resistance
      to structurally and functionally unrelated compounds, a property known as
      multidrug resistance (MDR). One MDR mechanism, i.e. by the overexpression of a
      plasma membrane protein, P-glycoprotein (P-gp), has been identified at the
      molecular level. The mdr1 gene-encoded P-gp acts as a drug efflux pump, lowering
      intracellular drug concentration by active extrusion of drugs from the cell. The
      role of P-gp in determining clinical resistance to multiple anticancer drugs is
      likely to be largely different for various tumor types. Recently we selected a
      monoclonal antibody (mAb LRP56) for strong, granular cytoplasmic reactivity with
      MDR tumor cell lines without P-gp (over)expression. None or weak reactivity was
      observed with parental and P-gp positive cell lines. We hypothesize that as yet
      undefined drug transport-mediating proteins are inserted in intracellular
      membranes lining the exocytotic compartment and thus may contribute to clinical
      multidrug resistance.

PMID- 1349271
TI  - During HIV-1 infection most blood dendritic cells are not productively infected
      and can induce allogeneic CD4+ T cells clonal expansion.
AB  - We have considered the possibility that antigen-presenting cells of the dendritic
      cell lineage may be infected in vivo and spread HIV-1 at the time dendritic cells
      initiate the clonal expansion of antigen-specific T cells. Dendritic cells were
      isolated from 25 HIV-1-infected subjects (CDC stages II-IV). Fewer dendritic
      cells were recovered from most infected subjects. Reduced numbers of total non-T
      cells were also found in these patients, so that preferential loss of dendritic
      cells did not occur. Dendritic cell function was assessed by stimulatory capacity
      for allogeneic CD4+ T cells in the mixed leucocyte reaction (MLR). Potent MLR
      stimulator activity was retained in the dendritic cell-enriched populations from
      HIV-infected patients. Seven out of nine patients without AIDS (asymptomatic,
      lymphadenopathy or ARC) and three out of six patients with AIDS had proliferative
      responses equivalent to those induced by dendritic cells from controls. Dendritic
      cells from HIV+ subjects were able to initiate the expansion of allogeneic CD4+ T
      cell clones with cloning efficiency not different from controls and without
      evidence of cytopathic effect in the expanding CD4+ clones. In situ hybridization
      of the different mononuclear cell populations with a gag-specific riboprobe
      demonstrated positive cells in the T cell fractions of 12 of the 15 patients
      tested. None of the asymptomatic or ARC patients had riboprobe-positive cells in
      the dendritic cell-enriched populations. Four out of nine patients with AIDS had
      cells positive for HIV-1 expression in the dendritic cell-enriched fraction.
      However, the positive cells had the nuclear profile of lymphocytes, and by
      cytofluorography some residual low-density T cells were present. By limiting
      dilution and polymerase chain reaction (PCR), CD4+ lymphocytes carried HIV
      provirus in inocula of 500-5000 cells, while provirus could only be detected in
      50,000 cells from the dendritic cell-enriched fraction. The latter signal may be
      due to the demonstrated levels of T cell contamination. Our data indicate that
      productive or latent HIV-1 infection of blood dendritic cells in vivo is rare,
      certainly no greater than in T lymphocytes, and that in vitro dendritic cell
      preparations from patients can expand CD4+ T cells efficiently and therefore may
      be able to expand T cells with immunotherapeutic activity.

PMID- 1349272
TI  - Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV-1
      diagnosis.
AB  - With the advent of standard flow cytometric methods using two-colour fluorescence
      on samples of whole blood, it is possible to establish the ranges of CD3, CD4 and
      CD8 T lymphocyte subsets in the routine laboratory, and also to assist the
      definition of HIV-1-related deviations from these normal values. In 676 HIV-1
      seronegative individuals the lymphocyte subset percentages and absolute counts
      were determined. The samples taken mostly in the morning. The groups included
      heterosexual controls, people with various clotting disorders but without
      lymphocyte abnormalities as well as seronegative homosexual men as the
      appropriate controls for the HIV-1-infected groups. The stability of CD4% and
      CD8% values was demonstrated throughout life, and in children CD4 values less
      than 25% could be regarded as abnormal. The absolute counts of all T cell subsets
      decreased from birth until the age of 10 years. In adolescents and adults the
      absolute numbers (mean +/- s.d.) of lymphocytes, CD3, CD4 and CD8 cells were 1.90
      +/- 0.55, 1.45 +/- 0.46, 0.83 +/- 0.29 and 0.56 +/- 0.23 x 10(9)/l, respectively.
      In patients with haemophilia A and B the mean values did not differ
      significantly. In homosexual men higher CD8 levels were seen compared with
      heterosexual men and 27% had an inverted CD4/CD8 ratio but mostly without CD4
      lymphopenia (CD4 less than 0.4 x 10(9)/l). However, some healthy uninfected
      people were 'physiologically' lymphopenic without having inverted CD4/CD8 ratios.
      When the variations 'within persons' were studied longitudinally over a 5-year
      period, the absolute CD4 counts tended to be fixed at different levels. As a
      marked contrast, over 60% of asymptomatic HIV-1+ patients exhibited low CD4
      counts less than 0.4 x 10(9)/l together with inverted CD4/CD8 ratios. Such
      combined changes among the heterosexual and HIV-1-seronegative homosexual groups
      were as rare as 1.4% and 3%, respectively. For this reason, when the lymphocyte
      tests show less than 0.4 x 10(9)/l CD4 count and a CD4/CD8 ratio of less than
      unity, the individuals need to be investigated further for chronicity of this
      disorder, the signs of viral infections such as HIV-1 and other causes of
      immunodeficiency.

PMID- 1349273
TI  - Expression of ICAM-1 (CD54) on normal and leukaemic B cells: implication for the
      mixed lymphocyte reaction.
AB  - Peripheral blood normal B lymphocytes were found to be poor stimulators in the
      mixed lymphocyte reaction (MLR), in contrast to normal activated B cells which
      were strong stimulators. This increased capacity to stimulate a strong MLR
      correlated with an increased expression of the ICAM-1 (CD54) molecule on the
      surface of these cells. Similarly, the capacity of leukaemic B cells to induce an
      allogenic stimulation in the MLR was limited to the ICAM-1 (CD54) positive
      leukaemic cells. The ability of normal activated or leukaemic B cells to induce
      an MLR was blocked by antibodies directed against ICAM-1.

PMID- 1349275
TI  - [Drug therapy of anxiety disorders].

PMID- 1349274
TI  - Effects of gastro-entero-pancreatic hormones upon triglyceride synthesis and
      secretion by rat hepatocytes.
AB  - To ascertain whether certain gastro-entero-pancreatic hormones whose
      concentration in blood rises after ingestion of food could play a role in the
      elevation of plasma triglycerides (or hepatic triglyceride secretion) observed
      after oral vs parenteral feeding, studies were undertaken of their acute effects
      upon triglyceride synthesis and release by freshly isolated rat hepatocytes in
      vitro. The incorporation of radiopalmitate into hepatocyte triglycerides was
      significantly increased, by one-fourth to one-half, by each of pancreatic
      polypeptide, peptide YY, and an intermediate concentration (0.50 microgram/mL) of
      somatostatin. However, at a lower concentration (0.25 microgram/mL) somatostatin
      significantly decreased (by 14%) the incorporation of radiopalmitate into
      hepatocyte triglycerides. Release of labelled triglycerides from hepatocytes into
      the medium was significantly enhanced by both gastric inhibitory polypeptide (by
      31%) and pancreatic polypeptide (22%), but was significantly reduced (by 28%) by
      somatostatin at a concentration of 1 microgram/mL. Neurotensin produced no
      detectable effect. Although there were similarities between the active hormones,
      each had a unique overall pattern of response on triglyceride synthesis and
      release and individually, or in concert with other hormones, could modulate
      hepatic triglyceride production and secretion, thereby explaining the
      differential effects of oral vs parenteral feeding on plasma triglycerides.

PMID- 1349276
TI  - [Glutamic acid antagonists as antiparkinson agents?].

PMID- 1349277
TI  - [Liver infarction after Whipple's surgery. Diagnosis based on clinical course and
      imaging procedures].
AB  - A 59-year-old woman who had undergone a Whipple's operation for carcinoma of the
      head of the pancreas, developed septic fever of up to 40 degrees C on the fourth
      postoperative day, accompanied by severe upper abdominal pain and local guarding
      on palpation over the liver. Her general condition markedly and quickly
      deteriorated. Liver abscess was suspected. Computed tomography demonstrated a
      hypodense, wedge-shaped lesion in the right lobe of the liver without any abscess
      capsule. Liver infarction was diagnosed when injection of contrast medium failed
      to show any increase in density. Magnetic resonance imaging confirmed the wedge
      shaped signal-rich lesion. Laboratory tests revealed a leucocytosis of
      30,000/microliters, a postoperative rise in serum alkaline phosphatase activity
      (up to 800 U/l), gamma-glutamyl transaminase (up to 190 U/l) and lactate
      dehydrogenase (up to 320 U/l), while GOT and GPT activities remained within
      normal limits throughout. Fever subsided within 3 weeks. --It is stressed that,
      if a patient's condition worsens after a major abdominal operation, liver
      infarction should be considered in the differential diagnosis. Modern imaging
      methods have increased the frequency of this diagnosis. They, together with the
      clinical picture and the pattern of biochemical tests, make it possible to
      distinguish reliably infarction from liver abscess.

PMID- 1349278
TI  - Prolactin-stimulated mitogenesis of cultured astrocytes.
AB  - PRL has been reported to activate cell cycle-specific enzyme markers in
      nonreproductive tissues. To determine if PRL stimulates cell cycle-specific
      markers and cell growth in the central nervous system, the effect of PRL on
      cellular proliferation was examined in cultured astrocytes. Astrocytes from
      confluent cultures were plated onto glass slides at a density of 2 x 10(4)
      cell/ml 24 h before use. In some experiments, cells were serum deprived for 24 h
      (Go-arrested) after plating. Cell proliferation was examined directly by an
      increase in cell number and in individual cells by immunofluorescent detection of
      proliferating cell nuclear antigen (PCNA) and the incorporation of 5-bromo-2'
      deoxyuridine (BrUd). When incubated with 1% serum, a small percentage (less than
      5%) of the cells expressed PCNA. In cells cultured with rat PRL (10(-10)-10(-7)
      M) for 18 h, staining of PCNA increased in a dose-dependent manner, with maximal
      expression occurring at 10(-9) M PRL. At concentrations above 10(-9) M, PCNA
      staining decreased. To examine the specificity of the PRL-induced increase in
      PCNA, cells were incubated in the presences of 10(-9) M rat (r) or bovine (b) GH.
      Whereas incubation of astrocytes with rPRL and bPRL activated PCNA, cells
      incubated with either rGH or bGH showed only a slight increase in the number of
      cells expressing PCNA. Further, incubation of astrocytes with 1 nM PRL in the
      presence of 100 nM cyclosporine, an immunosuppressive agent that specifically
      displaces PRL from its receptor, decreased the percentage of nuclei stained for
      PCNA to that observed in non-PRL-stimulated controls. Transient exposure of cells
      to 10(-9) M PRL for 30 min resulted in an increase in the number of cells
      expressing PCNA when cultured for 18 h in the presence of 1% serum. In the
      presence of 1% serum, 10(-9) M PRL increased the incorporation of BrUd and
      resulted in a 3-fold increase in the doubling rate. In cells incubated in serum
      free medium, only a few PCNA-positive cells could be detected. Treatment of Go
      arrested astrocytes with PRL (10(-10)-10(-7) M) for 18 h resulted in a dose
      dependent increase in the expression of PCNA. PCNA-positive cells were detected
      in cultures incubated with 10(-11) M PRL, with maximal expression at 10(-9)
      M.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1349279
TI  - Alpha-adrenergic input in the locus coeruleus modulates plasma
      adrenocorticotropin in cats.
AB  - Previous evidence suggested that noradrenergic activity in the vicinity of the
      ventrorostral locus coeruleus (LC) increased in response to hemorrhage. To
      investigate the possible role of this response in the control of ACTH release,
      microinjections (100 nl/min for 2 min) of several agents were made at 59 sites in
      35 cats anesthetized with chloralose. Injections were as follows: vehicle (all
      sites); 150 mM L-glutamate (GLU; 51 sites); an alpha 2-agonist, 1 mM clonidine
      (19 sites); an alpha 2-antagonist, 1 mM yohimbine (32 sites); an alpha 1-agonist,
      1 mM phenylephrine (PE; 42 sites); and an alpha 1-antagonist, 0.05 mM prazosin
      (20 sites). Plasma ACTH was measured by RIA. Responses were tested statistically
      by repeated measures analysis of variance. GLU at 12 sites in the region of the
      ventrorostral LC facilitated plasma ACTH (P less than 0.01), whereas GLU at 6
      sites in the caudal LC inhibited ACTH (P less than 0.05). Clonidine at 9 sites in
      an area that included the ventrorostral LC inhibited ACTH (P less than 0.05), and
      yohimbine at 7 sites within this latter area facilitated ACTH (P less than 0.01).
      PE within the ventrorostral LC had no effect on ACTH. However, PE at 10 sites
      within the caudal LC and along the ventromedial border of the ventrorostral LC
      facilitated ACTH. The responses for all of these areas to the respective agents
      differed from those to vehicle, whereas responses from other areas to the former
      agents or from all areas to prazosin did not. An increase in noradrenergic
      turnover in the LC may provide inhibitory alpha 2 modulation to the neurons in
      the LC that are activated by hemorrhage. This modulation and possible alpha 1
      input in areas adjacent to the ventrorostral LC may influence the hemodynamic
      control of ACTH release.

PMID- 1349280
TI  - Photoaffinity labeling of the somatostatin receptor: identification of molecular
      subtypes.
AB  - Pharmacological studies have suggested that the somatostatin (SS) receptor is
      heterogeneous and may exhibit subtypes selective for SS-14 and SS-28. Whether
      this heterogeneity can be explained by separate molecular forms of the receptor
      protein is unclear. In the present study, we have developed a novel
      photosensitive azido derivative of the octapeptide SS analog Tyr3 SMS (EE 581)
      and used it as a photoaffinity probe to characterize the molecular components of
      the SS receptor in five receptor positive tissues (normal rat brain, pituitary,
      pancreas, and adrenal cortex, and mouse AtT-20 pituitary tumor cells). [125I]EE
      581 labeled specific high affinity binding sites in all these tissues (Kd range
      1.3-1.67 nM). Photoaffinity labeled membrane SS receptors were analyzed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography.
      Three specifically labeled SS receptor proteins of 80 kilodaltons (kDa), 58 kDa,
      and 32 kDa were identified and exhibited a tissue-specific distribution. The 58
      kDa species was the exclusive form in pancreas, adrenal cortex, and AtT-20 cells
      and the dominant form in brain. The 32 kDa receptor protein was expressed as a
      minor form (ratio of 58 kDa:32 kDa 3:1), exclusively in brain. The 80 kDa
      receptor was found only in the pituitary where it occurred as the sole SS
      receptor species. Competition experiments showed that the 58 kDa and 32 kDa
      receptor proteins in brain reacted with SS-14 greater than SS-28; in contrast,
      the 58 kDa protein in AtT-20 cells bound SS-28 greater than SS-14 suggesting the
      existence of distinct subtypes of the 58 kDa receptor in these two tissues. These
      data represent the first systematic evaluation of the molecular forms of SS
      receptor proteins by photoaffinity labeling in different target tissues and
      provide direct evidence for molecular heterogeneity and SS-14/SS-28 selectivity;
      a major 58 kDa protein present in most tissues, an additional 32 kDa protein
      uniquely expressed in brain, and an 80 kDa protein exclusive to the normal
      pituitary.

PMID- 1349281
TI  - Nutritional and hormonal regulation of lipogenic-enzyme gene expression in rat
      liver.

PMID- 1349282
TI  - The carboxy-terminal lysine of alpha B-crystallin is an amine-donor substrate for
      tissue transglutaminase.
AB  - A hexapeptide, corresponding to the sequence around the glutamine in beta A3
      crystallin that functions as amine-acceptor for transglutaminase, was
      synthesized. This peptide was biotinylated and used as a probe to identify amine
      donor substrates for transglutaminase among lens proteins. It was found that
      Ca(2+)-activated transglutaminase linked this peptide not only to several beta
      crystallins but, unexpectedly, also to alpha B-crystallin. The C-terminal lysine
      residue of alpha B-crystalline could be identified as the site of linkage. This
      strengthens the notion that, at least in crystallins, all transglutaminase
      substrate residues are located in terminal extensions of the polypeptides. It was
      shown that in lens homogenate, alpha B-crystallin can be covalently crosslinked
      to beta-crystallins by transglutaminase. The transglutaminase-mediated
      crosslinking of alpha B-crystallin may have implications for its involvement in
      normal and pathological processes in lens and other tissues.

PMID- 1349283
TI  - Overexpression of the multidrug resistance gene product in adult rat hepatocytes
      during primary culture.
AB  - Expression of P-glycoprotein (P-gp), the product of multidrug resistance gene(s),
      was investigated in primary cultures of normal adult rat hepatocytes. Levels of P
      gp mRNAs determined by Northern blotting and of P-gp measured by immunoblotting
      increased in parallel with time in culture. As in normal liver, P-gp was found to
      be localized on the membrane of bile canaliculus-like structures. This increased
      expression of P-gp was associated with decreased intracellular retention of
      doxorubicin, which could be restored by compounds such as verapamil and
      cyclosporin; doxorubicin (and also vincristine) was more cytotoxic to early than
      to late cultures. As in preneoplastic and neoplastic liver, overexpression of P
      gp in cultured hepatocytes was associated with differential changes in drug
      metabolizing enzymes, including increased glutathione S-transferase 7-7.
      Functional P-gp over-expression was observed in the absence of xenobiotic
      exposure or cell division; it could be linked to cellular stress occurring during
      cell isolation and plating. Increased expression of P-gp was blocked by
      actinomycin D, indicating its dependence on increased transcription, while
      cycloheximide led to a superinduction suggesting negative regulation by a protein
      factor.

PMID- 1349284
TI  - Characteristics of the alpha 2/beta-adrenoceptor-coupled adenylate cyclase system
      and their relationship with adrenergic responsiveness in hamster fat cells from
      different anatomical sites.
AB  - Various studies have shown that the lipolytic response of white adipocytes to
      catecholamines was dependent on the anatomical origin of these cells. To provide
      a biological explanation for this phenomenon, we compared hamster white
      adipocytes, from femoral subcutaneous and epididymal fat, for their lipolytic
      activities, cAMP responses and adrenoceptor-coupled adenylate cyclase system.
      Basal and maximal lipolytic responses to the beta-adrenergic (isoproterenol) and
      the mixed alpha 2/beta-adrenergic (epinephrine) agonists were lower in femoral
      subcutaneous cells than in epididymal cells, but the alpha 2-adrenergic
      antilipolytic response to 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline bi
      tartate (UK14304) was slightly greater in femoral subcutaneous fat cells than in
      epididymal fat cells. Identical results were observed for cAMP responses, except
      for the alpha 2-adrenergic inhibitory response which was identical in both fat
      deposits. Adrenoceptors studies revealed higher density of inhibitory alpha 2
      adrenoceptors 2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline ([3H]RX821002
      binding sites) in femoral subcutaneous fat cells than in epididymal fat cells,
      but identical density of stimulatory beta-adrenoceptors (125I-cyanopindolol
      binding sites) and similar subdivision into beta-adrenoceptor subtypes in both
      adipose deposits. Finally, the level of the alpha-subunits of the stimulatory and
      inhibitors guanine-nucleotide-binding regulatory proteins, as well as the
      adenylate cyclase catalytic activity were 40-50% lower in femoral subcutaneous
      fat cell membranes than in epididymal fat cell membranes. These results suggest
      that the differences in cAMP and lipolytic responses to catecholamines between
      epididymal and femoral subcutaneous adipocytes result at least in part from site
      related differences in the adenylate cyclase system rather than in the
      adrenoceptor status.

PMID- 1349285
TI  - The characterization of a mutation of the 3' flanking sequence of the alpha 1
      antitrypsin gene commonly associated with chronic obstructive airways disease.
AB  - A restriction fragment length polymorphism (RFLP) of the 3' flanking region of
      the alpha 1-antitrypsin (AAT) gene, detected with the restriction enzyme TaqI,
      occurs in about 17% of patients with chronic obstructive airways disease (COAD).
      To characterize the mutation the sequence of this region of the normal AAT gene
      had to be determined. The sequence containing the site of the mutation was
      amplified by the polymerase chain reaction and the DNA was sequenced in six COAD
      patients. The mutation is a G to A transition and occurs in a region containing
      potential regulatory sequences corresponding to enhancer elements. It is as yet
      unclear if the mutation alters the expression of AAT.

PMID- 1349287
TI  - Potentiation of DNA damage by inhibition of poly(ADP-ribosyl)ation: a test of the
      hypothesis for random nuclease action.
AB  - Poly(ADP-ribosyl)ation is a cellular response to DNA strand breaks by which a
      large array of proteins becomes covalently modified for a brief period during the
      lifetime of the DNA breaks. Inhibition of poly(ADP-ribose) polymerase by 3
      aminobenzamide after many types of DNA damage leads to a marked increase in DNA
      strand breakage, repair replication, cytogenetic damage, mutagenesis, and cell
      killing. It has been hypothesized that poly(ADP-ribose) polymerase may modify
      potentially degradative endogenous nucleases that can reduce cellular viability.
      Thus, in the presence of DNA strand breakage, the polymer would bind these
      enzymes to inhibit their activity. When synthesis of the polymerase is inhibited,
      the enzymes would act randomly to produce nonspecific damage in the DNA. We
      tested this hypothesis by electroporating restriction enzymes into human cells
      containing the shuttle vector pHAZE. Restriction enzymes cleave at specific
      recognition sequences in the lacZ target gene of pHAZE, and mutations result from
      rejoining errors at the cleavage sites. If the hypothesis were correct, enzyme
      treated cells cultured with 3-aminobenzamide to inhibit synthesis of poly(ADP
      ribose) polymers would result in a significant increase in mutations outside the
      restriction enzyme sites. The spectrum of mutations observed after
      electroporation of PvuII (which produces blunt-end double-strand breaks) or PvuI
      (which produces cohesive-end double-strand breaks) was similar in untreated and 3
      aminobenzamide-treated cells. Thus, our results do not support the hypothesis
      that the increase in damage observed when poly(ADP-ribosyl)ation is inhibited is
      due to a chaotic, nonspecific attack on DNA by endogenous cellular nucleases.

PMID- 1349286
TI  - Apolipoprotein C-II deficiency syndrome due to apo C-IIHamburg: clinical and
      biochemical features and HphI restriction enzyme polymorphism.
AB  - We have characterized the clinical and biochemical features of three siblings of
      a kindred with severe hypertriglyceridaemia due to apolipoprotein C-II (apo C-II)
      deficiency caused by the mutation described as apo C-IIHamburg. The clinical
      syndrome is characterized by recurrent pancreatitis in two of three affected
      individuals, with discrete hepatosplenomegaly in all three patients and
      cholelithiasis in one. Eruptive xanthomas and lipemia retinalis were absent.
      Plasma lipoproteins were characterized by fasting chylomicronaemia, reduced low
      density lipoproteins (LDL) and low high density lipoproteins (HDL). The marked
      hypertriglyceridaemia could be corrected promptly by infusion of normal plasma.
      Apolipoprotein C-II (apo C-II) levels in homozygotes were very low (0.01 mg dl
      1), and mean apo C-II levels in heterozygotes were lower (2.08 +/- 0.11 mg dl-1)
      than in normal family members (3.38 +/- 0.75 mg dl-1). Lipoprotein lipase and
      hepatic triglyceride lipase activities in post-heparin plasma were normal. Zonal
      ultracentrifugation revealed a marked increase in triglyceride-rich lipoproteins
      and reduced LDL and HDL. LDL consisted of two fractions with higher hydrated
      density of the main fraction compared with normals with a trend to normalization
      on a fat-free diet. The molecular defect in the apo C-II Hamburg gene has been
      previously identified as a donor splice site mutation in the second intron. This
      leads to abnormal splicing of the apo C-II Hamburg mRNA and apo C-II deficiency
      in plasma. The mutation causes the loss of an HphI restriction enzyme site
      present in the normal apo C-II gene.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349288
TI  - Seroprevalence of antibodies to hantaviruses and leptospires in selected Italian
      population groups.
AB  - A study of hantaviral and leptospiral antibodies in selected population groups
      was performed. Among high risk subjects in the Rome area, Hantaan antibody was
      found in mammalogists (10%) and dialysis patients (6%), while none of the
      trappers, oarsmen, river policemen and firemen studied tested positive for
      antibodies to hantaviruses. In occupationally-exposed subjects (farmers, rangers,
      lumbermen, hunters) from rural and densely forested areas of northern Italian
      regions, the prevalence of Hantaan antibody ranged from 3.3% to 8.8%. In the
      positive cases the comparative antibody titration using different hantaviruses
      showed a predominance of Hantaan virus (titer 1:128) compared to Puumala virus
      (titer 1:32); no reactivity was observed with Seoul or Prospect Hill viruses. In
      Rome, leptospiral antibodies were found in trappers (21%) and oarsmen (5%) at a
      titer of 1:50 or more, with a predominance for the L. icterohaemorrhagiae
      serotype (85%). In the Alpine areas the leptospiral antibody prevalence was 12%
      and L. icterohaemorrhagiae and L. bratislava were the predominant serotypes. The
      presence of hantavirus infections, suspected after the first epidemiological
      survey conducted in central Italy, is now supported by the new data obtained in
      northern Italian regions. Furthermore, the recent observation of one case of
      Hemorrhagic Fever with Renal Syndrome (HFRS) in the Udine area, not far from the
      Yugoslavian border, strongly confirms the presence of one or more hantaviruses in
      Italy.

PMID- 1349289
TI  - Nonsurgical repair of perforation defects. Internal matrix concept.
AB  - The internal matrix concept of perforation repair offers distinct advantages over
      classic techniques. The biocompatible matrix allows control of the repair
      material. The technique sensitivity involved with placement of the repair
      material is reduced and contamination of the restorative material with hemorrhage
      is prevented. In accessible locations perforations can be repaired predictably
      and, by comparison, the prognosis is improved greatly. Fewer surgeries or
      surgical alterations of teeth will be necessary, thus reducing the cost of
      treatment. A higher percentage of existing crowns can be salvaged if surgical
      alteration of the tooth is prevented. Microsurgical techniques currently are
      being developed and researched that may allow nonsurgical repair of inaccessible
      perforations. The scope of endodontic therapy, therefore, will be expanded.

PMID- 1349290
TI  - Characterization of a Drosophila melanogaster gene similar to the mammalian genes
      encoding the tyrosine/tryptophan hydroxylase activator and protein kinase C
      inhibitor proteins.
AB  - A cloned 1.3-kb cDNA that hybridizes to genomic clone 549, containing genes
      predominantly expressed in the head of Drosophila melanogaster, was
      characterized. DNA sequencing showed that the cDNA-encoded protein is similar to
      a family of mammalian proteins, called 14-3-3, which activate tyrosine
      hydroxylase (TyrOHase) and tryptophan hydroxylase (TrpOHase), the two key enzymes
      regulating biosynthesis of biogenic monoamine neurotransmitters, such as dopamine
      and serotonin, in the brain. The putative D. melanogaster 14-3-3 protein (D14-3
      3) shares 72.4, 74.3 and 78.3% amino acid (aa) sequence identity and 83.5, 87.7
      and 85.9% aa sequence similarity with the beta, gamma and eta forms of bovine 14
      3-3 protein, respectively. A lower (71%), but significant level of aa sequence
      identity was also found between D14-3-3 and sheep brain protein kinase C
      inhibitor protein (KCIP). The D14-3-3 gene expresses 1.0-, 1.9- and 2.9-kb mRNAs
      which show differential expression patterns. While the 2.9-kb mRNA is expressed
      only in the head, the other two mRNAs are found both in the head and body.
      Compared to the 1.9- and 2.9-kb mRNAs, the 1.0-kb mRNA is more abundant in the
      ovary and is probably maternally inherited. The 1.9-kb mRNA is the most
      predominant species in the embryos and its level peaks between 6-15 h of
      embryogenesis. The D14-3-3 gene is predominantly expressed in the ventral nerve
      cord of the embryo, and in the neural tissues of the head.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1349291
TI  - [Somatostatin: therapeutic value in external gastrointestinal fistulas].

PMID- 1349292
TI  - Possible epidemiological factors associated with rupture of the posterior tibial
      tendon.
AB  - Rupture of the posterior tibial tendon has been postulated to occur, in part, as
      a result of degenerative changes to the tendon. This possibility was examined by
      a review of 67 patients (average age 57 years) diagnosed with rupture of the
      posterior tibial tendon. Forty-five of the 67 patients (60%) had one or more of
      the following positive medical histories: (1) hypertension, (2) obesity, (3)
      diabetes mellitus, (4) previous surgery or trauma about the medial aspect of the
      foot, or (5) steroid exposure. Thirty-five patients (52%) had either
      hypertension, diabetes mellitus, or obesity. A statistical correlation was
      demonstrated between rupture of the posterior tibial tendon and obesity (P =
      .005) and to a lesser extent hypertension (P = .025). These disorders have been
      uniformly associated with an acceleration of the degenerative processes
      associated with aging, commonly via an acceleration of microvascular and
      macrovascular diseases. An additional vascular risk is implicated by the known
      zone of hypovascularity of the posterior tibial tendon and risk of rupture
      secondary to systemic or local injections of corticosteroids. The prevalence of
      posterior tibial tendon rupture parallels the degenerative processes of aging,
      hypertension, diabetes mellitus, and obesity. Additionally, the effects of
      corticosteroids and local surgical procedures may further be associated with
      local vascular impairment and eventual rupture.

PMID- 1349293
TI  - Management of acquired adult dropfoot.
AB  - Dropfoot is a catchall term for ankle equinus, equinovarus, and equinovalgus. The
      deformity can be flexible or rigid and may be associated with other pathology. In
      the adult, dropfoot may be congenital or acquired. Acquired dropfoot results from
      weakness of the ankle dorsiflexors, overpull of the plantarflexors, contracture
      of the soft tissues, bony deformity, or any combination of these factors.
      Appropriate treatment includes observation, orthotic devices, bracing, tendon
      transfers, arthrodesis, and neurolysis. The purpose of this paper is to review
      the pathophysiology and treatment of acquired dropfoot.

PMID- 1349294
TI  - The effect of endogenous somatostatin upon human thyrotrophin (TSH) secretion.
AB  - Two studies were performed to determine the importance of endogenous somatostatin
      (SS) in regulating human TSH secretion. In the first, healthy adult males were
      studied in random order on two occasions a week apart. They were infused with
      either saline to maintain euglycaemia, or 10% dextrose to raise blood glucose
      concentration by at least 3 mmol/L within 10 minutes, and cause hypothalamic SS
      release. Fifteen minutes after the infusions were commenced, 200 micrograms of
      TRH was injected intravenously and TSH release was followed for the next 75
      minutes. In the second study, persons with elevations of TSH to between 3 and 12
      mU/L were also infused with either saline or 10% dextrose. Infusions were
      continued for 1 hour and the TSH secreted was measured over this time period.
      There was no significant difference between the euglycaemic or hyperglycaemic
      studies in TRH-induced TSH secretion, either as areas under the curve, or as mean
      values at individual times. Mean TSH peaks were seen in both groups at 25 minutes
      post-TRH. Mean peak values were 8.11 +/- 0.97 mU/L (mean +/- SEM) in the
      euglycaemic group, and 7.94 +/- 1.18 mU/L in the hyperglycaemic group. Mean area
      under the curve was 396.3 +/- 53.2 mU/L/75 mins (SEM) for the euglycaemic study
      and 385.1 +/- 59.5 mU/L/75 mins (SEM) for the hyperglycaemic group. In the
      infusion study in the persons with mild hypothyroidism, there was no difference
      in TSH concentration between the two infusion regimes. These results show that in
      acute studies, hyperglycaemia does not inhibit human TSH release, despite the
      likelihood of hypothalamic-pituitary SS concentration being increased.

PMID- 1349295
TI  - Confidentiality and the family as caregiver.
AB  - Many families provide mentally ill relatives with a residence and other support.
      Although professionals increasingly acknowledge the importance of the supportive
      role families play, families continue to report that they receive too little
      information from professionals about the patient, particularly when the family
      acts as caregiver. The authors suggest that mental health professionals' views
      about confidentiality may prevent them from providing information to families and
      urge professionals to rethink the issue of confidentiality and its application to
      families acting as caregivers. The authors conclude that certain information
      about a patient can--and should--be shared with families who are in a caregiver
      role without violating clinical, legal, or ethical principles.

PMID- 1349296
TI  - Sperm typing allows accurate measurement of the recombination fraction between
      D3S2 and D3S3 on the short arm of human chromosome 3.
AB  - The interval between the D3S2 and D3S3 loci on human chromosome 3p is a frequent
      site of deletions in a number of different cancers and contains the most common
      fragile site in man. Both loci have been physically mapped to 3p but because
      heterozygosity for D3S3 is so infrequent, recombination between them could not be
      determined accurately by using family studies. Sperm typing can measure
      recombination between DNA polymorphisms even in a single individual and thus can
      make use of polymorphisms with a low PIC. The recombination fraction between D3S2
      and D3S3 was estimated to be 0.28 based on analyzing 189 and 77 sperm from two
      doubly heterozygous donors, respectively. These results demonstrate one of the
      ways in which sperm typing can complement pedigree analysis in constructing
      genetic maps.

PMID- 1349297
TI  - Molecular cloning, characterization, and genomic localization of a human
      potassium channel gene.
AB  - Potassium (K+) channels are critical for a variety of cell functions, including
      modulation of action potentials, determination of resting membrane potential, and
      development of memory and learning. In addition to their role in regulating
      myocyte excitability, cardiac K+ channels control heart rate and coronary
      vascular tone and are implicated in the development of arrhythmias. We report
      here the cloning and sequencing of a k+ channel gene, KCNA1, derived from a human
      cardiac cDNA library and the chromosomal localization of the corresponding
      genomic clone. Oligonucleotides based on a delayed rectifier K+ channel gene were
      used in PCR reactions with human genomic DNA to amplify the S4-S6 regions of
      several different K+ channel genes. These sequences were used to isolate clones
      from a human cardiac cDNA library. We sequenced one of these clones, HCK1. HCK1
      contains putative S2-S6 domains and shares approximately 70% sequence homology
      with previously isolated Shaker homologues. HCK1 was used to screen human cosmid
      libraries and a genomic clone was isolated. By sequencing the genomic clones, a
      putative S1 domain and translation initiation sequences were identified. Genomic
      mapping using human-rodent somatic cell panels and in situ hybridization with
      human metaphase chromosomes have localized KCNA1 to the distal short arm of human
      chromosome 12. This work is an important step in the study of human cardiac K+
      channel structure and function and will be of use in the study of human inherited
      disease.

PMID- 1349298
TI  - Localization of the nucleotide excision repair gene ERCC6 to human chromosome
      10q11-q21.
AB  - We have cloned the human DNA excision repair gene ERCC6 by virtue of its ability
      to correct the uv sensitivity of Chinese hamster overy cell mutant UV61. This
      mutant is a member of complementation group 6 of the nucleotide excision repair
      deficient rodent mutants. By means of in situ hybridization and Southern blot
      analysis of mouse x human somatic cell hybrids, the gene was localized to human
      chromosome 10q11-q21. An RFLP detected within the ERCC6 locus can be helpful in
      linkage analysis.

PMID- 1349299
TI  - DNA restriction fragment analysis of the somatostatin gene in familial isolated
      growth hormone deficiency type I.
AB  - The somatostatin (SST) gene was analyzed to detect possible molecular variations
      in subjects with familial isolated growth hormone deficiency type I (IGHD I). No
      gross alterations in restriction fragments were observed with 18 used enzymes.
      The association with two RFLPs closely linked to the SST gene was also negative,
      adding weight to the evidence that the SST gene is not involved in the etiology
      of IGHD I. The nucleotide variability of a 23-kb DNA segment containing the SST
      gene and its flanking sequences was studied by restriction analysis of a sample
      of 19 Italians. The data suggest that approximately 1 in 400 bp is variant in
      this region.

PMID- 1349300
TI  - Proliferative lymphocyte responses to foot-and-mouth disease virus and three FMDV
      peptides after vaccination or immunization with these peptides in cattle.
AB  - We studied proliferative responses of bovine T lymphocytes to foot-and-mouth
      disease virus (FMDV) serotypes A, O and C as well as to three peptides including
      the two major B-cell epitopes of FMDV (VP1[141-156] and VP1[200-213]). Peripheral
      blood mononuclear cells (PBMC) from cattle previously vaccinated with monovalent
      vaccine responded to both homotypic and heterotypic virus strains. Of 14 FMDV
      specific bovine T-cell clones, which were prepared from PBMC of an animal
      vaccinated with the trivalent vaccine, 11 reacted to each of the three serotypes
      A, O and C. This indicates that several T-cell epitopes might be conserved among
      these serotypes. PBMC from one of two cattle immunized with VP1[141-156]KLH, one
      of two cattle immunized with VP1[200-213]KLH and two of three cattle immunized
      with CC-VP1[200-213]-PPS-VP1[141-156]-PCG responded to the homotypic virus
      strain. After immunizations with VP1[200-213]KLH also heterotypic responses were
      found. Thus, it appears that these two B-cell sites include T-cell determinants
      that are recognized by some cattle. However, when proliferative responses of PBMC
      from an animal vaccinated with the trivalent vaccine were tested, no responses
      were found to VP1[141-156] and VP1[200-213], whereas the response was very poor
      to CC-VP1[200-213]-PPS-VP1[141-156]-PCG. These results suggest that these
      sequences do not represent dominant T-cell epitopes and/or that T-cell reactivity
      towards these synthetic peptides does not completely cover the T-cell reactivity
      towards the fragments present after processing of the whole virus.

PMID- 1349301
TI  - Management of the non-descended testis: doubtful value of luteinizing-hormone
      releasing-hormone (LHRH). A double-blind, placebo-controlled multicentre study.
AB  - In a double-blind, placebo-controlled multicentre study, the effect of
      luteinizing-hormone-releasing-hormone (LHRH) in 141 boys was analysed after 4
      week treatment period with 0.4 mg LHRH nasal spray or placebo nasal spray three
      times daily. Data from 123 boys was analysed, with 62 boys in the treatment group
      and 61 in the placebo group. Full response i.e. the testis at the bottom of the
      scrotum on both sides in boys with bilaterally undescended testes, was found in
      six patients, one of them in the placebo group [Therapeutic gain of LHRH with 95%
      CI: 8.1% (0.1-16.6%, P = 0.12)]. Only in these boys could surgery be avoided.
      Considering the number of testes (and not the number of boys) a significant
      effect was found on at least one testis in 25% of boys with bilaterally
      undescended testes [Therapeutic gain with 95% CI: 24.0% (13.2-34.8%, P = 0.001)].
      In unilateral undescended testes, the LHRH treatment showed no effect (P = 1.00).
      The inclusion of retractile testes did not affect our results. In our opinion
      LHRH has a limited place in treatment of the non-descended testis.

PMID- 1349302
TI  - Aortic dissection following transluminal angioplasty of the thoracic aorta in
      nonspecific aortoarteritis.
AB  - We performed transluminal angioplasty for an eccentric, calcific stenosis of the
      thoracic aorta in a patient with nonspecific aortoarteritis and encountered an
      iatrogenic aortic dissection. Follow-up by intravenous digital subtraction
      angiography at 12 hours and at one week showed no change in the picture. He is
      asymptomatic at 6 months except for residual hypertension. Eccentric, localized
      thoracic stenosis may constitute an unfavourable angiographic morphology for
      angioplasty.

PMID- 1349303
TI  - Effects of subminimal inhibitory concentrations of ampicillin on hemagglutination
      of Escherichia coli.
AB  - The hemagglutination (HA) activity of Escherichia coli was enhanced by subminimal
      inhibitory concentrations (sub-MICs) of ampicillin. One half of the MIC of
      ampicillin caused a bacterial filamentation and diminished bacterial piliation
      (as observed by light and electron microscopies) as well as an increase of HA
      activity. HA activity, however, decreased after separation of ampicillin-treated
      bacteria. These results indicate that the increase in HA activity by ampicillin
      is mainly due to filament formation.

PMID- 1349304
TI  - Harvesting of the internal mammary artery: a short and safe extrapleural route.

PMID- 1349305
TI  - Expression of unique sets of GPI-linked proteins by different primary neurons in
      vitro.
AB  - We have surveyed the proteins expressed at the surface of different primary
      neurons as a first step in elucidating how axons regulate their ensheathment by
      glial cells. We characterized the surface proteins of dorsal root ganglion
      neurons, superior cervical ganglion neurons, and cerebellar granule cells which
      are myelinated, ensheathed but unmyelinated, and unensheathed, respectively. We
      found that the most abundant proteins are common to all three types of neurons.
      Reproducible differences in the composition of the integral membrane proteins
      (enriched by partitioning into a Triton X-114 detergent phase) were detected.
      These differences were most striking when the expression of glycosylphosphatidyl
      inositol (GPI)-anchored membrane proteins by these different neurons was
      compared. Variations in the relative abundance and degree of glycosylation of
      several well known GPI-anchored proteins, including Thy-1, F3/F11, and the 120-kD
      form of the neural cell adhesion molecule (N-CAM), and an abundant 60-kD GPI
      linked protein were observed. In addition, we have identified several potentially
      novel GPI-anchored glycoproteins on each class of neurons. These include a
      protein that is present only on superior cervical ganglion neurons and is 90 kD;
      an abundant protein of 69 kD that is essentially restricted in its expression to
      dorsal root ganglion neurons; and proteins of 38 and 31 kD that are expressed
      only on granule cell neurons. Finally, the relative abundance of the three major
      isoforms of N-CAM was found to vary significantly between these different primary
      neurons. These results are the first demonstration that nerve fibers with diverse
      ensheathment fates differ significantly in the composition of their surface
      proteins and suggest an important role for GPI-anchored proteins in generating
      diversity of the neuronal cell surface.

PMID- 1349306
TI  - Serologic confirmation of simian T-lymphotropic virus type I infection by using
      immunoassays developed for human T-lymphotropic virus antibody detection.
AB  - Serum specimens from diverse species of Old World monkeys, categorized as
      seropositive (n = 97) or seronegative (n = 23) for human T-lymphotropic virus
      (HTLV) infection, were tested by using recombinant env-spiked Western immunoblot
      assays and synthetic peptide assays for simultaneous detection and discrimination
      of simian T-lymphotropic virus (STLV) infection. Of the 97 seropositive
      specimens, 93 reacted with the recombinant transmembrane (r21env) protein and 90
      reacted with a recombinant, MTA-1, derived from the central region of the
      external glycoprotein of HTLV-I (rgp46env), thus yielding test sensitivities of
      96 and 93%, respectively. While 1 of the 23 negative monkey specimens reacted
      with r21env, none reacted with rgp46env, for overall specificities of 96 and
      100%, respectively. Analysis of synthetic peptide-based immunoassays demonstrated
      that while 85 of 97 (88%) seropositive specimens reacted with HTLV-I-specific
      epitope (p19gag), none of the specimens reacted with HTLV-II-specific epitope
      (gp52env). These results show that recombinant envelope-spiked Western blots
      provide a simple means for serologic confirmation of STLV-I infection and that
      type-specific synthetic peptides can be used to confirm the virus type in
      seropositive monkey specimens.

PMID- 1349307
TI  - Molecular characterization of strains of enteroinvasive Escherichia coli O143,
      including isolates from a large outbreak in Houston, Texas.
AB  - A large diarrhea outbreak due to enteroinvasive Escherichia coli (EIEC) serogroup
      O143 occurring in Houston, Tex., provided the opportunity to investigate aspects
      of the molecular epidemiology of this and related organisms. This was done by
      comparing the plasmid patterns and the chromosomal restriction endonuclease
      digestion patterns by pulsed-field gel electrophoresis (PFGE) of EIEC from the
      outbreak, other E. coli from the same serogoup (O143), and EIEC isolated from
      other patients with diarrhea. Among the isolates studied, there was marked
      restriction fragment length polymorphism. All 3 non-O143 EIEC isolates had very
      different restriction endonuclease digestion patterns, as did 5 of 5 O143 non
      EIEC isolates and 6 of 15 O143 EIEC isolates. Four Houston outbreak O143 EIEC
      isolates had the same restriction pattern as an O143 EIEC strain isolated 2
      months before in Mexico and was nearly identical to another two O143 EIEC Mexican
      isolates. These related strains also had the same plasmid pattern; however, the
      presence of only a few plasmid bands, versus the 21 to 30 chromosomal bands seen
      with PFGE, suggests that plasmid patterns could be a less specific way to
      distinguish different strains. These results demonstrate that PFGE can
      distinguish between different E. coli strains of the same serogroup and
      phenotype. This technique can also identify relatedness within O143 EIEC, and our
      data suggest the spread of a strain of EIEC from Mexico to Houston, where it
      caused a large outbreak. PFGE may be useful to study the epidemiology of EIEC.

PMID- 1349309
TI  - Are any antianxiety agents safer for patients who spend a great deal of time in
      direct sunlight?

PMID- 1349308
TI  - Neuroleptic malignant syndrome.

PMID- 1349310
TI  - Converging GABA- and glutamate-immunoreactive axons make synaptic contact with
      identified hypothalamic neurosecretory neurons.
AB  - To study the neurochemical identity of axons in synaptic contact with identified
      hypothalamic neurosecretory neurons in rats, we combined retrograde axonal
      transport of a marker molecule with postembedding immunogold staining for amino
      acid neurotransmitters. After intravenous injections of horseradish peroxidase,
      neurosecretory neurons with axons in the median eminence or neurohypophysis
      transported the peroxidase retrogradely back to the cell body of origin. Serial
      ultrathin sections from the paraventricular and arcuate nuclei were immunostained
      with glutamate or GABA antisera. Peroxidase-labeled neurons and their dendrites
      received synaptic contact from colloidal gold-labeled axons immunoreactive for
      GABA or for glutamate. Axons which were highly immunoreactive for GABA and other
      axons immunoreactive for glutamate but not for GABA consistently made converging
      synaptic contact with the same peroxidase-labeled cell. Some of the peroxidase
      labeled neurons from the arcuate nucleus which were postsynaptic to both GABA and
      glutamate axons were themselves identified as being GABA immunoreactive. Serial
      ultrathin sections revealed that multiple presynaptic axons immunoreactive for
      glutamate or GABA made repeated contacts with single neurons. These results
      suggest a widespread convergence of the major inhibitory and excitatory amino
      acid transmitter on the neurons which control both the anterior and posterior
      pituitary hormones.

PMID- 1349311
TI  - Neuropeptide Y (NPY) and C-flanking peptide of NPY in the pineal gland of normal
      and ganglionectomized sheep.
AB  - The present immunohistochemical study describes the presence and distribution of
      nerve fibers containing neuropeptide Y (NPY), and C-Flanking Peptide Of NPY
      (CPON) in the pineal gland of the sheep. Nerve fibers were detected by using a
      series of antisera directed against NPY or against CPON. Many positive
      immunoreactive nerve fibers were identified in the pial capsule of the pineal, in
      connective septae and in the parenchyma between pinealocytes. The
      intraparenchymal fibers were particularly evident and created an extensive
      network throughout the gland. Nerve fibers immunoreactive for all the peptides
      were also observed in the posterior commissure and in the stria medullaris
      thalami. No NPY- or CPON-positive neurons were found in the pineal gland. In
      order to study the site of origin of NPY- and CPON-immunoreactive nerve fibers,
      the superior cervical ganglia were bilaterally removed in a series of animals.
      Sympathetic denervation was checked by using an antiserum against tyrosine
      hydroxylase (TH). Nearly all TH-immunoreactive elements disappeared in the pineal
      glands of animals sacrificed 15 days after surgery. Also the density of NPY- and
      CPON-immunoreactive nerve fibers decreased in the animals after the
      ganglionectomy. However, a number of nerve fibers still remained in the gland.
      These data indicate that some NPY- and CPON-immunoreactive nerve fibers of the
      sheep pineal gland derive from an extrasympathetic origin. The very dense
      innervation of the sheep pineal gland with nerve fibers containing NPY and CPON
      strongly indicates a functional role for this family of peptides in the pineal
      gland of this species.

PMID- 1349312
TI  - Transmitter diversity in ganglion cells of the guinea pig gallbladder: an
      immunohistochemical study.
AB  - Several neurotransmitters have been reported to exist in the ganglionated plexus
      of the guinea pig gallbladder. These include substance P, neuropeptide Y (NPY),
      calcitonin gene-related peptide, vasoactive intestinal peptide (VIP),
      acetylcholine, norepinephrine, serotonin, and dopamine. To determine which
      neuropeptides are intrinsic to gallbladder ganglia, we performed
      immunohistochemistry on colchicine-treated preparations. In separate, single
      labeled preparations, a majority of neurons contained substance P-, NPY-, or
      somatostatin-like immunoreactivity. In double-labeled preparations, a large
      majority of the neurons that contained substance P-like immunoreactivity also
      contained NPY-like immunoreactivity and somatostatin-like immunoreactivity.
      Immunoreactivity for VIP was present in a small percentage of the gallbladder
      neurons which did not contain substance P-like immunoreactivity. Additional
      experiments were done to test for the presence of other compounds, known to exist
      in the neurons of the gut. Although immunoreactivity was found in control
      preparations of small intestine, the ganglionated plexus of the gallbladder
      lacked immunoreactivity for galanin, dynorphin, enkephalin, gastrin-releasing
      peptide, or gamma-aminobutyric acid. We conclude that ganglia of the guinea pig
      gallbladder contain at least two populations of neurons, based on transmitter
      phenotype. One of these populations appears to contain substance P, NPY, and
      somatostatin. Another population, which represents a small contingent of the
      total population of neurons, contains VIP.

PMID- 1349313
TI  - Ontogeny of somatostatin immunoreactivity in the cat retina.
AB  - In the ganglion cell layer of the adult cat retina, subgroups of displaced
      amacrine cells and alpha ganglion cells are immunoreactive for somatostatin or a
      somatostatinlike substance. Both types of immunoreactive cells are found
      preferentially in inferior retina. We studied the development of somatostatin
      immunoreactivity in the prenatal and postnatal cat retina to determine how such
      unusual distributions of immunoreactive cells arise. Somatostatin-immunoreactive
      profiles were first observed at embryonic day (E) 30, within the inner retina in
      a central region that included the optic disk and the area centralis. By E36,
      immunoreactivity had virtually disappeared from the central retina but was
      present throughout the periphery. The immunoreactive profiles could not be
      classified morphologically because of their immaturity but were most likely
      retinal ganglion cells, the earliest born cells of the inner retina. Of the two
      types of immunoreactive cell observed in the adult, the first to be recognized
      morphologically was the displaced amacrine cell, at E45. These cells were
      virtually adultlike in morphology and number by E51, two weeks before birth. In
      contrast, immunoreactive alpha ganglion cells were not apparent until five days
      after birth and did not achieve their mature numbers and immunoreactive staining
      characteristics until more than a month later. From the time they could initially
      be recognized, both immunoreactive displaced amacrine cells and alpha cells were
      distributed mainly in the inferior retina. A third type of somatostatin
      immunoreactive cell was transiently observed in the superior and inferior retina
      during prenatal and early postnatal development. These cells were characterized
      by granular staining in irregular shapes and few, if any, faintly stained
      processes. Injections of retrograde tracers into retinorecipient targets revealed
      that many of these cells were retinal ganglion cells. They disappeared by
      postnatal day 38. Our results indicate that somatostatin immunoreactivity
      initially follows a central-to-peripheral pattern of development, as is typical
      of other developmental events in the mammalian retina. They also indicate that
      the two types of somatostatin-immunoreactive neurons present in the adult cat
      retina (displaced amacrine and alpha ganglion cells) attain their mature
      immunocytochemical properties with very different timecourses. Finally, the
      observation that somatostatin immunoreactivity appears transiently in the
      granular-staining ganglion cells, distributed throughout the superior and
      inferior retina, suggests that the peptide may play a regulatory role in the
      development of the retina and/or retinofugal pathways.

PMID- 1349314
TI  - Self-help and benzodiazepine withdrawal.
AB  - Despite an increased understanding of the potential dangers of benzodiazepines
      among doctors and patients, and a decline in anxiolytic prescribing, motivating
      and supporting current benzodiazepine users through withdrawal can be difficult
      and time consuming for medical services. Self-help organisations offer another
      approach. This is a study of one such organisation, TRANX (UK), which examined
      the characteristics of its members and their outcome. The results suggest that
      this organisation did provide effective counselling and support for its members,
      and implies that self-help is a realistic alternative or adjunct to orthodox
      health care for those wishing to withdraw from benzodiazepines.

PMID- 1349315
TI  - Ipecac abuse--danger.
AB  - Ipecac abuse must be considered when working with individuals at risk,
      particularly those with eating disorders. Medical complications such as myopathy
      and gastrointestinal and other toxic effects can occur with ipecac abuse, the
      gravity of which must not be underestimated. Education about ipecac abuse and
      toxicity is extremely important. Discontinuation of ipecac use usually results in
      recovery from the harmful effects. College healthcare professionals can play an
      important role in the education and treatment of this potentially hazardous
      method of weight control.

PMID- 1349316
TI  - Myositis ossificans of traumatic origin in the foot.
AB  - This case reviews a myositis ossificans of traumatic origin discovered beneath
      the fifth metatarsal in an adult male. Details of its anatomic appearance are
      illustrated with the assistance of plane film roentgenography and magnetic
      resonance imaging. Histologic sections are included to support the diagnosis and
      present characteristic cellular patterns. A review of the literature including
      etiology, clinical classification, and diagnostic criteria are also presented.

PMID- 1349317
TI  - Immunocytochemical localization of the ectoenzyme aminopeptidase N in the human
      breast.
AB  - The ectoenzyme aminopeptidase N (APN) was localized in the normal human breast at
      both the light microscopic and the ultrastructural level. APN was expressed on
      intralobular and interlobular fibroblasts and on the apical surface of some
      luminal epithelial cells. This enzyme was not detected on either myoepithelial
      cells and their associated basement membrane or capillary endothelium.
      Furthermore, the staining pattern was maintained in benign and malignant breast
      disease. APN belongs to a family of enzymes that hydrolyze peptides in the
      extracellular space. As with other ectoenzymes present in the breast, APN
      expression is restricted to specific cell types. This pattern of expression may
      indicate a role for these enzymes in the biology of the normal breast.

PMID- 1349318
TI  - Histochemical staining of protein-tyrosine phosphatase activity in primary human
      mammary carcinoma: relationship with established prognostic indicators.
AB  - Protein-tyrosine phosphatase (PTPase) activity in frozen human mammary primary
      carcinoma tissue sections has been quantitated using a modified histochemical
      assay. The improved method features the assay of PTPase activity in 12-microns
      sections of air-dried unfixed tissues, and the use of [2-(N-morpholino)
      ethanesulfonic acid] (MES) buffer to prepare stable reaction solutions. Tissue
      samples from 53 primary human mammary carcinomas were assayed for PTPase
      activity, and immunohistochemically stained for c-erbB-2 protein-tyrosine kinase
      expression. Elevated levels of PTPase activity were found in 68% of the tumors
      compared with the level of activity found in normal human mammary tissues. PTPase
      activity was co-localized with pathology definitive for carcinoma. Excessive
      activity was demonstrated throughout the cell, with high activity evident in the
      cell cytoplasmic membrane and the nucleus. Coexistence of elevated expression of
      c-erbB-2 and increased PTPase activity was present in 53% of the tumors. In
      contrast, 15% displayed low c-erbB-2 expression and high PTPase activity, and 24%
      displayed high c-erbB-2 expression and low PTPase activity. No statistically
      significant association was found between increased PTPase activity and either c
      erbB-2 overexpression or grade and stage of disease in primary human mammary
      tumors.

PMID- 1349319
TI  - Imaging early steps of human T cell activation by antigen-presenting cells.
AB  - In this work the Ca2+ response and the morphological changes elicited by Ag in
      human CD4+ T cells are described at the single cell level. The APC used to
      present the diphtheria toxoid Ag to a human diphtheria toxoid-specific T cell
      clone were murine L cell fibroblast transfectants expressing MHC class II
      molecules. The increase of the intracellular Ca2+ concentration, [Ca2+]i, which
      is one of the earliest steps of the response to TCR stimulation, was followed by
      fluorimetry with fura-2 on an imaging system. This response was a specific
      consequence of successful Ag presentation, because it only took place when
      fibroblasts expressed both class II MHC molecules and Ag. CD4 molecules were also
      involved in this intercellular interaction, because the Ca2+ response could be
      inhibited by preincubating the T cells with an anti-CD4 antibody. The response
      induced by APC started after a delay of at least 6 min, after which large Ca2+
      oscillations took place, with a pseudo period of 100 s at 35 degrees C. The
      frequency of these oscillations decreased with temperature. The oscillations
      became progressively more damped during the first 30 to 40 min of cell-to-cell
      interaction, after which they completely stopped; however, [Ca2+]i remained well
      above its resting level for more than 1 h after the contact. The Ca2+
      oscillations were entirely dependent on Ca2+ influx because they immediately
      disappeared when external calcium was removed. Similar oscillations were observed
      when the cells were stimulated with an anti-CD3 antibody. After stimulation with
      APC, many T cells abandoned their spherical shape and tended to flatten and
      elongate. This aspect of the T cell response was not observed after stimulation
      with an anti-CD3 antibody. In the presence of cytochalasin B, the morphologic
      changes elicited by the APC were blocked, whereas the Ca2+ response was slightly
      enhanced. However, when T cells were loaded with the Ca2+ chelator BAPTA, both
      Ca2+ and morphologic changes were inhibited, suggesting that the Ca2+ response
      plays a permissive role for the morphologic changes.

PMID- 1349320
TI  - Regulation of locomotion and cell-cell contact area by the LFA-1 and ICAM-1
      adhesion receptors.
AB  - We demonstrate complementary differences in the behavior of B lymphoblastoid
      cells adhering to LFA-1 or its counter-receptor ICAM-1. The interaction of B
      lymphoblastoid cells with glass-supported planar bilayers bearing LFA-1 or ICAM-1
      was observed by time-lapse video microscopy, and the distribution of adhesion
      receptors on cells interacting with the planar bilayers was studied by
      immunofluorescence microscopy. B lymphoblasts formed a large contact area and
      crawled rapidly (up to 25 microns/min) on planar bilayers bearing ICAM-1. In
      contrast, these cells attached to planar bilayers bearing LFA-1 through a fixed
      point about which the cells actively pivoted, using a single stalk-like
      projection. Phorbol ester-stimulated lymphoblasts, which adhere more strongly to
      ICAM-1-bearing substrates than unstimulated lymphoblasts, were still capable of
      locomotion on ICAM-1. Phorbol ester stimulation of B lymphoblasts on planar
      bilayers bearing LFA-1 promoted a rapid conversion from "stalk" attachment to
      symmetrical spreading of the cell on the substrate. Cellular LFA-1 remained
      uniformly distributed on the cell surface during interaction with bilayers
      bearing purified ICAM-1 as determined by immunofluorescence. In contrast, ICAM-1
      was concentrated in the stalk-like structure through which the unstimulated B
      lymphoblasts adhered to LFA-1 in planar bilayers, but ICAM-1 immunofluorescence
      became more uniformly distributed over the cell surface within minutes of phorbol
      ester addition. Neither LFA-1 or ICAM-1 colocalized with the prominent staining
      of filamentous actin in the ruffling membrane regions. Interaction through cell
      surface LFA-1 and ICAM-1, 2, or 3 promotes different cellular morphologies and
      behaviors, the correlation of which with previously observed patterns of
      lymphocyte interaction with different cell types is discussed.

PMID- 1349321
TI  - A protein kinase C-activating phorbol ester accelerates the T cell antigen
      receptor-stimulated phosphatidylinositol cycle in normal human CD4+ T cells.
AB  - Ligation of the TCR on Jurkat T lymphoblastoid cells causes an 1,4,5-inositol
      trisphosphate-dependent rise in intracellular cytoplasmic calcium that is
      inhibited by PMA, a potent activator of protein kinase C. Consequently, protein
      kinase C is widely believed to mediate feedback inhibition of TCR-activated
      phospholipase C. We have now extended these studies to normal unblasted human
      CD4+ T lymphocytes, examining the PMA sensitivity of both the TCR complex
      mediated release of total inositol-phosphates and the resynthesis of the parent
      phosphoinositides. In contrast to Jurkat, in which PMA inhibited release of 1,4,5
      inositol trisphosphate by 60% and total inositolphosphates by 40% (50% inhibitory
      concentration, 5.6 nM), normal cells displayed a marked increase in anti-CD3
      induced phosphatidylinositol (PI) cycling in the presence of PMA. Both total
      inositolphosphate release and PI resynthesis were maximally elevated (88% and
      342%, respectively) by a PMA concentration that also optimally supported a
      subsequent proliferative response; the ED50 was at least 11.7-fold lower than
      that for the inhibitory effect of PMA on breakdown of total Jurkat PI. A PKC
      nonactivating phorbol ester had no effect. If anti-CD3 was replaced by the
      mitogenic lectin PHA, PI resynthesis was similarly up-regulated by PMA in these
      highly purified cells. The PMA up-regulatory phenomenon was not a simple
      consequence of cell blastogenesis, inasmuch as there was no early effect on the
      non-signaling-associated phosphatidylethanolamine compartment after CD3
      stimulation. Thus, PKC activation appears to accelerate TCR-linked PI metabolism
      in normal Th cells, in contrast to the feedback inhibitor paradigm observed in
      Jurkat and other tumor cell systems.

PMID- 1349322
TI  - Cytotoxic T lymphocyte response against multiple simian immunodeficiency virusA
      (SIV) proteins in SIV-infected macaques.
AB  - To identify the target proteins of CD8+ T lymphocytes we have explored the
      cytolytic immune responses of 12 rhesus macaques experimentally infected with the
      simian immunodeficiency virus (SIVmac). Target cells were autologous B cell lines
      presenting SIVmac proteins after infection with recombinant vaccinia viruses. The
      eight following proteins were studied: ENV, POL, GAG, NEF, VIF, REV, TAT, and
      VPX. Macaque PBMC stimulated with Con A and expanded in T cell growth factor
      containing medium produced cell lines with cytolytic activity in the majority of
      infected animals (9/12). The structural proteins ENV, POL, and GAG were
      recognized by cell lines derived from nine, eight, and six macaques,
      respectively. The small regulatory proteins also represented efficient CTL
      targets, a specific activity being detected against NEF (8/12), REV (7/12), VPX
      (7/12), TAT (6/12), and VIF (5/12). Most cytotoxic responses (except those
      directed against ENV) were mediated by CD8 cells and were MHC class I restricted.
      Limiting dilution analysis allowed us to quantify the frequency of CTL precursors
      and confirmed the high immunogenicity of multiple SIV proteins. Three different
      patterns of response could be defined: six animals were able to recognize at
      least six of the eight tested target proteins, two of them reacting with all
      eight target proteins. The other three responder macaques reacted only against a
      few SIV proteins, whereas no cytotoxic activity was detected in the three
      remaining infected macaques and in the nine negative controls. The six animals
      responding against multiple proteins were still healthy 12 to 22 mo after
      infection with two of them presenting a decrease in circulating CD4 cells
      concurrently to the disappearance of the CTL response. Conversely, three
      nonresponder or low responder macaques developed an overt disease after 4 to 12
      mo, and two other presented a very low level of CD4 cells, suggesting that the
      pattern of response may be of prognostic value.

PMID- 1349323
TI  - A nuclear DNA-binding protein expressed during early stages of B cell
      differentiation interacts with diverse segments within and 3' of the Ig H chain
      gene cluster.
AB  - We have used electrophoretic mobility shift assays (EMSA) to detect B cell
      lineage-specific nuclear proteins that bind to diverse segments within and 3' of
      the Ig H chain gene cluster. DNA binding sites include sequences 5' of each of
      the following C region genes: mu, gamma 1, gamma 2a, epsilon, and alpha. For the
      most part, these binding sites lie 5' of CH-associated tandem repeats. Binding
      sites for the same B cell lineage-specific proteins have also been defined in the
      region 3' of C alpha, close to a recently described B cell-specific enhancer
      element. Cross-competition of EMSA indicates that the B cell lineage-specific
      nucleoprotein is indistinguishable from those described previously by others: S
      alpha-BP and BSAP. Because of the diverse sequences recognized by this protein,
      we term it NF-HB, B-lineage-specific nuclear factor that binds to Ig H gene
      segments. EMSA using segments 5' of S gamma 2a (5'S gamma 2a-176) and 3' of C
      alpha (3' alpha-88) shows multiple binding complexes, two of which are B cell
      lineage specific. The B cell-specific complex with fastest mobility contains only
      NF-HB, and the one with slowest mobility contains NF-HB together with a
      ubiquitous DNA-binding protein(s). The ubiquitous binding protein is different
      for 5' S gamma 2a-176 and for 3' alpha-88, representing the formation of protein
      NF-HB complexes specific for these particular Ig DNA regions. Spleen cells show a
      single band upon EMSA with either 5'S gamma 2a-176 or 3' alpha-88. Upon LPS
      stimulation, additional binding complexes of slower mobility were formed
      resulting in a pattern comparable to those detected in pro-B, pre-B, and B cell
      lines. We hypothesize that NF-HB may promote physical interactions between the 3'
      alpha-enhancer and segments of the Ig H gene cluster.

PMID- 1349324
TI  - Termination of the B cell lymphoma dormant state in thymectomized AKR mice.
AB  - AKR mice are highly susceptible to spontaneous T cell lymphomagenesis and thymus
      removal at the age of 1 to 3 mo greatly reduces its development. Twelve-mo-old
      AKR mice thymectomized at young age were shown previously to carry potential
      lymphoma cells that could be triggered to develop into B cell lymphomas (80 to
      100%) after removal from their host "restrictive" environment into young
      histocompatible hosts. Additional attempts were made to terminate the potential
      lymphoma cell dormant state in 12-mo-old thymectomized AKR mice. Replenishment of
      some deficiencies caused by thymectomy at a young age, including a s.c. syngeneic
      thymus graft or a single injection of the dual tropic recombinant virus isolates
      DTV-71 or MCF-247 into 12-mo-old thymectomized AKR mice resulted in Ly-1+ pre-B
      or B cell lymphoma development in 80 to 98% of these treated mice. In vivo
      elimination of T cell subsets by administration of cyclosporin A or by mAb
      expressed on Th cells (anti-CD4) or cytotoxic T cells (anti-CD8) stimulated the
      progression of dormant potential lymphoma cells towards B cell lymphoma
      development. The most striking results were observed after administration of anti
      CD8 mAb: 90 to 100% of these treated mice developed Ly-1+ B cell lymphomas within
      80 days. The effect of rIL-2 on dormant PLC was also tested. Administration of
      rIL-2 to 12-mo-old thymectomized mice terminated tumor dormancy in 94% of the
      treated mice within 66 days. Tests of the resulting B lymphomas for dual tropic
      recombinant virus/mink cell focus-inducing virus infection indicated that the
      breakdown of tumor dormancy did not result from development of pathogenic class I
      mink cell focus-inducing viruses. These results suggest that T cell subsets
      and/or their products are involved in the proliferation arrest of potential
      lymphoma cells present in thymectomized AKR mice.

PMID- 1349325
TI  - CD4-CD8+ T lymphocytes mediate AKR/gross murine leukemia virus nonresponsiveness
      in moderately aged AKR.H-2b:Fv-1b mice.
AB  - Previously we reported that as AKR.H-2b:Fv-1b mice become older than 9 wk of age
      they begin to specifically lose the ability to generate anti-AKR/Gross murine
      leukemia virus (MuLV) CTL responses after immunization and in vitro restimulation
      with cells expressing AKR/Gross MuLV-encoded Ag. Interestingly, the frequency of
      virus-specific precursor cytotoxic T lymphocytes (CTL) observed in moderately
      aged AKR.H-2b:Fv-1b mice was not substantially decreased from that found in their
      young responder counterparts. To further investigate the mechanism(s) responsible
      for the inability of moderately-aged AKR.H-2b:Fv-1b mice to mount AKR/Gross MuLV
      specific CTL responses, adoptive transfer experiments were performed in the
      present study. Transferring splenocytes from moderately-aged AKR.H-2b:Fv-1b
      donors into young AKR.H-2b:Fv-1b recipients resulted in inhibition of AKR/Gross
      MuLV-specific CTL responsiveness. Anti-Thy-1.1 plus complement depletion of T
      cells from the donor cell population before adoptive transfer resulted in a near
      complete restoration of AKR/Gross MuLV responsiveness of young recipient AKR.H
      2b:Fv-1b mice suggesting that the inhibition observed in moderately aged mice was
      mediated by T lymphocytes. Additional experiments using depletion of T subsets
      before cell transfer demonstrated that inhibition of AKR/Gross MuLV-specific CTL
      responsiveness was mediated by a CD4-CD8+ T lymphocyte.

PMID- 1349326
TI  - Enhancement of radiation-induced base release from nucleosides in alkaline
      solution: essential role of the O.- radical.
AB  - The effect of pH on base release in the gamma-radiolysis of N2O-saturated
      solutions of a number of nucleosides (including uridine, 3-methyluridine, 2',3'-O
      isopropylidene-uridine, and adenosine) has been investigated. For all these
      nucleotides, independent of the base or sugar moiety, base release is very low at
      pH below 10 (G approximately (0.3-0.7) x 10(-7) mol J-1), but increases
      drastically to G approximately (3-4) x 10(-7) mol J-1 at pH greater than or equal
      to 13. This phenomenon had already been previously reported and attributed to an
      OH(-)-induced transfer of a base radical into a sugar radical. However, it is now
      shown that at pH 12, where base release starts to increase, a lowering of the
      dose-rate does not affect the yield of free base. The increase in base release is
      accompanied by an overall reduction of chromophore loss of similar magnitude
      (with 2',3'-O-isopropylidene-uridine and 3-methyluridine), as well as by an
      increase in the yield of oxidizing radicals by a factor of 2 (with uridine). The
      measured rate constant of the reaction of .OH/O.- with the nucleosides is also pH
      dependent, as .OH reacts faster than O.- with the nucleosides by a factor of 6-7.
      It is concluded that the increase in base release at high pH is caused by the
      increasing participation of O.-, which, unlike .OH, attacks the nucleosides
      preferentially at their sugar moieties, and is not due to an OH(-)-induced
      radical transfer from the base to the sugar moiety.

PMID- 1349327
TI  - Internucleosomal DNA cleavage should not be the sole criterion for identifying
      apoptosis.

PMID- 1349328
TI  - Relationships between DNA damage and the survival of radiosensitive mutant
      Chinese hamster cell lines exposed to gamma-radiation. Part 1: Intrinsic
      radiosensitivity.
AB  - In this study we used the neutral elution technique (at pH 9.6) to compare the
      efficiency of DNA double-strand break (dsb) induction and cell killing in two
      radiosensitive Chinese hamster ovary cell lines, EM9 and NM2, and their parent
      cell line, AA8, after exposure to low doses (2.5-12 Gy) of 137Cs gamma-radiation.
      The survival curves indicated that at all radiation doses examined EM9 cells were
      the most radiosensitive and AA8 cells were the least radiosensitive. We found
      significant differences among the three cell lines in the neutral elution assay.
      While NM2 cells showed the same immediate postirradiation dose response for DNA
      damage as the parent cell line, EM9 cells showed a two-fold greater elution rate
      than AA8 cells per unit dose. Either the dsb induction efficiency was greater in
      EM9 than in AA8 cells, or the same frequency of dsb in EM9 and AA8 cells gave
      rise to a different DNA elution rate, perhaps because of differences in their
      chromatin structure. We also used a mitotic selection technique to examine the
      duration of the gamma-ray-induced mitotic delay in the three cell lines. Mitotic
      delay was less severe in NM2 cells than in AA8 cells, but was significantly
      longer in EM9 cells than in AA8 cells. Thus the measurements obtained using both
      neutral elution and mitotic selection suggest that the underlying molecular bases
      of the radiosensitivity of EM9 and NM2 cells are very different.

PMID- 1349330
TI  - The intrinsic alpha/beta ratio for human tumour cells: is it a constant?
AB  - The radiation response of 15 mammalian cell lines comprising 11 human tumour, two
      human fibroblast and two murine lymphoma cell lines, has been analysed using the
      linear-quadratic equation. As well as using conventional analysis of acute dose
      survival curves to derive values for alpha and beta (termed alpha ac and beta
      ac), low dose-rate and split-dose experiments have been used to derive
      independent values of alpha and beta (alpha 1dr and beta RR), respectively. alpha
      1dr provides a measure of irrecoverable damage, the magnitude of which agreed
      well with the initial slope of the acute survival curve for most cell lines. beta
      RR derived from split-dose experiments represents a unique measure of recovery
      for each cell line. Large differences were found between individual values of
      beta ac and beta RR, especially in the radiosensitive cell lines. Since beta RR
      is a functional measure of recovery we suggest that this is the more relevant
      parameter in studies of dose sparing. The most striking result of this analysis
      was found in considering the alpha/beta ratios. No relationship was observed
      between alpha ac and beta ac resulting in values of alpha ac/beta ac ranging from
      1 to 175. In contrast a positive correlation was observed between alpha 1dr beta
      RR in the 11 tumour cell lines, giving an alpha/beta ratio of 9.4 +/- 1.8 Gy.
      This observation of the relative constancy of the ratio for human tumour cells
      leads to an hypothesis about the role of initial damage as a determinant of
      radiosensitivity.

PMID- 1349329
TI  - Radiosensitization efficacy of KU-2285, RP-170 and etanidazole at low radiation
      doses: assessment by in vitro cytokinesis-block micronucleus assay.
AB  - Since the cytokinesis-block micronucleus assay is very sensitive at low radiation
      doses, we used it to investigate the in vitro sensitizing effects of two new
      hypoxic cell sensitizers (KU-2285, a fluorinated 2-nitroimidazole and RP-170, a 2
      nitroimidazole nucleoside analogue) at 1-3 Gy in comparison with etanidazole.
      Exponentially growing EMT6 cells were treated with the drugs under aerobic or
      hypoxic conditions for 40 min prior to and during irradiation, after which the
      drugs were removed and cytochalasin B (2 micrograms/ml) was added to the medium.
      The number of micronuclei in binucleate cells was counted after 42 h of culture.
      Under aerobic conditions the three compounds at 5 mM had no sensitizing effect.
      Under hypoxic conditions the sensitizer enhancement ratio (SER) at 5 mM was 3.8
      for KU-2285, 3.2 for RP-170, and 2.3 for etanidazole, while the oxygen
      enhancement ratio was 2.9. When the cells were pretreated under hypoxic
      conditions with drugs at 5 mM but then irradiated under aerobic conditions, KU
      2285 and RP-170 had a sensitizing effect whereas etanidazole did not. The
      sensitizers were also tested at 0.5 and 1 mM, and the SER values were compared
      with those obtained at high doses (15-30 Gy) using a colony assay. The SER at low
      doses was higher than that at high doses for 1 and 5 mM KU-2285 and 5 mM RP-170,
      while the SERs were similar for all concentrations of etanidazole and the lower
      concentrations of KU-2285 and RP-170. These results might suggest the potential
      usefulness of KU-2285 and RP-170 in clinical radiotherapy.

PMID- 1349331
TI  - Murine haemopoietic stem cells with long-term engraftment and marrow repopulating
      ability are more resistant to gamma-radiation than are spleen colony forming
      cells.
AB  - The radiation sensitivity of various subsets in the haemopoietic stem cell
      hierarchy was defined using a limiting dilution type long-term bone marrow
      culture technique that was previously shown to allow quantification of cells with
      spleen colony-forming potential (day-12 CFU-S) and in vivo marrow repopulating
      ability (MRA). Primitive stem cells that generate new in vitro clonable colony
      forming cells (CFU-C) in the irradiated marrow (MRA) and have long-term
      repopulation ability (LTRA) in vitro (cobblestone area forming cell, CAFC day-28)
      had D0 values of 1.25 and 1.38 Gy, respectively. A lower D0 was found for the
      less primitive CFU-S day-12, CAFC day-12 and cells with erythroid repopulating
      ability (0.91, 1.08 and 0.97 Gy, respectively). CFU-S day-7 were the most
      radiosensitive (D0 equalling 0.79 Gy), while CFU-C and CAFC day-5 were relatively
      resistant to irradiation (D0 1.33 and 1.77 Gy). Split-dose irradiation with a 6 h
      interval gave dose sparing for stem cells with MRA and even more with in vitro
      LTRA, less for CFU-S day-12 and CAFC day-10 and none for CFU-S day-7. The cell
      survival data of the specified stem cell populations were compared with the
      ability of a fixed number of B6-Gpi-1a donor bone marrow cells to provide for
      short- and long-term engraftment in single- and split-dose irradiated congenic B6
      Gpi-1b mice. Serial blood glucose phosphate isomerase (Gpi) phenotyping showed
      less chimerism in the split as compared to the single radiation dose groups
      beyond 4 weeks after transplant. Radiation dose-response curves corresponding to
      stable chimerism at 12 weeks for single and fractionated doses revealed
      appreciable split-dose recovery (D2-D1) in the order of 2 Gy. This was comparable
      to D2-D1 estimates for MRA and late-developing CAFC (1.27 and 1.43 Gy,
      respectively), but differed from the poor dose recovery in cells corresponding to
      the committed CFU-S day-7/12 and CAFC day-10 population (0.14-0.33 Gy). These
      data are together consistent with differential radiosensitivity and repair in the
      haemopoietic stem cell hierarchy, and provide a cellular basis for explaining the
      dose-sparing effect of fractionated total-body irradiation conditioning on long
      term host marrow repopulation.

PMID- 1349332
TI  - Radiation dose as a factor in host preparation for bone marrow transplantation
      across different genetic barriers.
AB  - Engraftment of donor bone marrow in relation to total body irradiation (TBI) dose
      was studied in syngeneic (B6----B6), MHC-compatible (BALB.B----B6) and MHC
      incompatible allogeneic (BALB/c----B6) murine bone marrow transplantation (BMT)
      models. For each BMT combination radiation dose-response curves were obtained
      from stable long-term bone-marrow chimerism using Gpi-1 phenotyping and this was
      compared with the growth of exogenous CFU-S. Syngeneic engraftment required the
      lowest TBI doses limited to ablation of host haemopoietic stem cells. Resistance
      against H-2-compatible allogeneic engraftment was evident at low radiation doses
      (less than 5.5 Gy) but at 6 Gy and above the level of chimerism was comparable to
      syngeneic transplants, which indicated effective immunosuppression. Higher TBI
      doses were needed for engraftment as the immunological barrier was increased
      using fully H-2-incompatible allogeneic transplants. The high TBI dose (9.5 Gy)
      needed for suppression of spleen endocolonies in the CFU-S assay meant that
      rejection of exogenous bone marrow was evident only across the larger
      immunological barriers. When the fully allogeneic combination was reversed (B6---
      BALB/c) both CFU-S and chimerism data showed less rejection. The steep dose
      response relationships show how engraftment is critically dependent on TBI dose,
      as well as the genetic disparity between donor and host.

PMID- 1349333
TI  - Radioprotection of mice by the bacterial extract Broncho-Vaxom: haemopoietic stem
      cells and survival enhancement.
AB  - Pretreatment of mice with 50-1000 micrograms of the bacterial extract Broncho
      Vaxom (BV, free of endotoxin) before sublethal irradiation induced an increase in
      the number of endogenous haemopoietic stem cells (E-CFU). The degree of
      radioprotection was dependent on both the time of administration and the dose of
      BV. An optimal E-CFU survival was observed when 500 micrograms of BV was
      administered i.p. 24 h before irradiation. BV did not affect the day 9 CFU-S
      survival in the bone marrow directly after irradiation. However, 5, 9 and 12 days
      after irradiation, the number of day 9 CFU-S was almost 2-fold higher in the bone
      marrow of BV injected mice. Pretreatment with BV protected C57B1/6 mice in a dose
      dependent manner from the lethal effect of ionizing radiation. A single dose (50,
      100, 250, or 500 micrograms) of bacterial lysate injected i.p. 24 h before 9.5 Gy
      gamma-rays (LD100/21) protected 16%, 25%, 80%, and 94% of C57B1/6 mice,
      respectively. The dose reduction factor in the case when the BV (500 micrograms
      per mouse) was administered at that time was 1.18 (95% CL 1.12, 1.25).

PMID- 1349334
TI  - Haematological effects of rhGM-CSF in dogs exposed to total-body irradiation with
      a dose of 2.4 Gy.
AB  - It was the specific aim of this study to test the stimulatory effects of
      recombinant human GM-CSF (rhGM-CSF) on haemopoietic regeneration in dogs which
      had received total-body irradiation (TBI) with a dose of 2.4 Gy. In normal dogs
      rhGM-CSF given subcutaneously at 10 microgram/kg per day or 30 microgram/kg per
      day for 21 days caused strong but transient increases in the peripheral blood
      neutrophils. The monocyte counts also showed a transient rise during treatment in
      a dose-dependent fashion, whereas the lymphocyte counts increased only at the
      higher dose of rhGM-CSF and the platelet counts were transiently depressed during
      the course of the treatment. In the irradiated animals treatment with rhGM-CSF
      decreased the severity and shortened the duration of neutropenia but had no
      significant influence on monocyte or lymphocyte recovery. The granulocyte values
      showed a characteristic pattern of fluctuations with the first peak occurring at
      the same time (day 10 to day 13) when the abortive rise was observed in the
      untreated dogs. In contrast the GM-CFC in the peripheral blood remained depressed
      during the whole treatment course, similar to the untreated irradiated controls.
      These results indicate that treatment with GM-CSF can be an effective biological
      monotherapy for radiation-induced bone marrow failure, but that for higher
      radiation doses the number of GM-CSF responsive target cells will become a
      critical determinant of therapeutic efficacy.

PMID- 1349336
TI  - Effect of ionizing radiation on neuromuscular junctions in mouse tongues.
AB  - Radiation damage to the neuromuscular junctions (NMJs) in mouse tongues was
      studied using local x-irradiation of the tongues with the rest of the body
      shielded. Transmission electron microscopy (TEM) revealed no significant
      morphological changes in the fine structures and organelles of the NMJs given 4
      Gy. A dose of 8 Gy produced degenevative morphological changes associated with
      oxon terminal sprouting as early as 2 and 7 days following irradiation.
      Subsequently, 1-11 weeks later, severe degenerative changes were observed. The
      number of mitochondria was significantly decreased with increased occurrence of
      degenerative membranal features. The number of synaptic footplates without
      terminals or with multiple small terminals within one groove increased gradually
      with time. Most of these pathological changes persisted for at least 3 months
      after irradiation. However, the myofibres, blood vessels and interstitial cells
      appeared to be unaffected throughout the period of follow-up. The present study
      substantiates our previous reports of ageing-like changes in the tongues' NMJs
      induced by their excessive exposure to free radicals.

PMID- 1349335
TI  - Topical or systemic 16, 16 dm prostaglandin E2 or WR-2721 (WR-1065) protects mice
      from alopecia after fractionated irradiation.
AB  - Our previous studies in mice demonstrated that systemic or topical 16,16 dm PGE2
      protected against single dose radiation-induced hair loss. We have now
      investigated prostaglandin, or WR-2721, protection against murine alopecia
      produced by varying doses and schedules of fractionated radiation. On days one to
      eight after hair was plucked from the thighs of B6D2F1 mice, groups of 6 animals
      each were given daily exposures of 4.0 or 4.5 Gy for 5 days; 2.5, 3.5, 4.5 or 5.5
      Gy for 10 days; or 2 Gy for 15 days. One hour before irradiation each mouse
      received 10 microgram 16,16 dm PGE2, either by subcutaneous injection into the
      neck or topical application, 8 mg WR-2721 by injection, or 0.3 mg WR-1065 by
      topical application. Three weeks later counts of regrowing hairs were recorded
      from excised skin samples. For the radioprotectors used, hair regrowth was
      increased 25-100% in the various radiation groups in comparison to irradiated
      only control sites. In some studies with the radioprotector given systemically,
      WR-2721 afforded slightly greater radioprotection than 16,16 dm PGE2. The two
      compounds were essentially equally radioprotective in the topical application
      studies. Since both systemic and topical applications of the agents tested
      enhanced hair regrowth following radiation, we conclude that clinical use of
      these compounds may provide some protection of hair follicles, and perhaps other
      tissues, lying within a radiation therapy field.

PMID- 1349337
TI  - A freezing technique applicable to transformation studies of C3H10T1/2 cells.

PMID- 1349338
TI  - Simultaneous measurement of cell cycle phase position and ionizing radiation
      induced DNA strand breakage in single human tumour cells using laser scanning
      confocal imaging.
AB  - Techniques for the assessment of DNA damage and repair in individual cells are
      pertinent to several areas of research, in particular the study of the
      heterogeneity of tumour cell populations in response to anticancer agents. We
      describe an adaptation of an in situ alkaline denaturation assay performed on
      individual nuclei of lysed cells, termed nucleoids, trapped within an agarose
      film. A novel aspect of the technique described in the application of confocal
      laser scanning fluorescence microscopy for the measurement of nucleoid relaxation
      in response to DNA damage. The volumes of spherical nucleoids and their relative
      DNA contents were determined by ethidium bromide staining and the analysis of
      confocal sections through the equatorial planes of the nucleoids. Mean nucleoid
      volume increased as a linear function of X-ray dose (0.5-8 Gy) administered to
      intact cells prior to lysis. We provide evidence of heterogeneity, in
      asynchronous cultures, in the DNA unfolding/unwinding characteristics of cells
      irrespective of cell cycle age. Bivariate plots of relative DNA content versus
      nucleoid volume allowed the direct assessment of cellular repair capacity with
      respect to cell cycle position.

PMID- 1349339
TI  - Comparison of hepatitis B virus subtyping of d/y determinants by
      radioimmunoprecipitation assay and the polymerase chain reaction.
AB  - Using a double polymerase chain reaction a method was devised for detecting and
      subtyping hepatitis B virus DNA in serum samples. Primers from the S-gene were
      selected from the sequence analyses of five HBV HBsAg subtypes, to amplify HBV
      DNA and subtype for y specific DNA. Thirty-eight samples were subtyped for d and
      y determinants by radioimmunoprecipitation assay (RIPA) and the polymerase chain
      reaction (PCR). Subtyping by PCR and RIPA was in agreement in 100% of subtype y
      samples and 83.3% of subtype d, giving an overall correlation of 92.1%. As a
      third comparison, 12 amplified samples were digested by the restriction enzyme
      Sau 3A, which differentiates between subtypes y and d. The digest results agreed
      with PCR in 83.3% of the samples. In addition, we compared our standard
      phenol/chloroform extraction against a rapid one step method. The
      phenol/chloroform stage was found to be essential for the removal of nucleases
      and polymerase inhibitors present in sera.

PMID- 1349340
TI  - Antibodies to Epstein-Barr virus and cytomegalovirus in relation to CD4 cell
      number in human immunodeficiency virus 1 infection.
AB  - Interaction between herpesviruses and human immunodeficiency virus (HIV)1 is
      postulated in the progression of HIV disease. In order to evaluate the specific
      antibody responses directed to Epstein-Barr virus (EBV) and cytomegalovirus (CMV)
      and to provide serological evidence suggesting reactivation of these viruses able
      to accelerate the immunodeficiency, we studied IgA and IgG titres to EBV and CMV
      in the serum of HIV positive patients in relation to the CD4 cell number. The
      titres of IgG antibodies to EBV and the prevalence of IgG to CMV were
      significantly higher in HIV positive patients compared to control high risk HIV
      negative subjects. In HIV infected patients, anti-VCA IgG antibodies increased
      and anti-EBNA IgG antibodies decreased progressively in relation to the decline
      of CD4 cell number whereas anti-CMV IgG antibodies did not varied significantly
      at the same time. Anti-VCA IgA and anti-EA IgG antibodies were found uncommonly
      and with low titres. IgA antibodies to EA and CMV were not detected in any
      patient. The variations in EBV antibody response that we describe in HIV
      infection were previously reported in other immunodeficiency states and could be
      distinctive of these diseases.

PMID- 1349341
TI  - Sensitization of dopamine-stimulated adenylyl cyclase in the striatum of 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys and patients with
      idiopathic Parkinson's disease.
AB  - Dopamine-stimulated adenylyl cyclase activity was measured in striatal
      homogenates of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus
      monkeys and humans with idiopathic Parkinson's disease and compared with the
      activity in control tissue. No differences between parkinsonian and control
      tissue were found in the presence of 20 mM NaCl. However, when 120 mM NaCl was
      included in the assay medium, a significantly higher increase in the Vmax of
      dopamine-stimulated adenylyl cyclase activity was observed in the caudate of MPTP
      parkinsonian rhesus monkeys and the putamen of patients with idiopathic
      Parkinson's disease. No such sensitization was seen in the MPTP-treated rhesus
      putamen or human Parkinson's disease caudate tissue. A role of D2 receptors in
      this sensitization could be ruled out by the concomitant use of the D2 antagonist
      l-sulpiride and by [3H]spiperone saturation analysis of the D2 receptor density,
      which was found at control level in the caudate tissue of MPTP-treated rhesus
      monkeys. Similarly, on the basis of saturation binding with the D1 selective
      ligand 125I-SCH 23982, there was no difference in caudate nucleus D1 receptor
      densities between control and MPTP-treated monkeys. Our results point to a region
      specific functional sensitization of D1 receptors as a consequence of severe
      dopaminergic denervation of the striatum and suggest the possibility of a
      therapeutic potential of a D1 agonist with full intrinsic activity in Parkinson's
      disease.

PMID- 1349342
TI  - Sequences that direct rat tyrosine hydroxylase gene expression.
AB  - Investigation of neuroendocrine genes has revealed that transcription is
      regulated via multiple DNA binding sites, including the cyclic AMP response
      element (CRE). We show here that for the neuronal and chromaffin-specific gene
      tyrosine hydroxylase (TH), a 70-bp region (-229 to -160) lacking the CRE is
      sufficient, in either orientation, to confer levels of chloramphenicol
      acetyltransferase reporter expression equivalent to or greater than that
      conferred by 4.8 kb of the rat TH enhancer/promoter region. The 70-bp region
      contains potential binding sites for AP2, AP1, E2A/MyoD, and POU transcription
      factors, and functions when linked to the TH promoter, but not when joined to a
      heterologous RSV promoter. This demonstrates that promoter as well as enhancer
      elements are important for TH expression. In gel-shift assays, the 70-bp fragment
      forms a cell type-specific complex with nuclear extracts from TH-expressing
      cells. which is effectively competed by an oligonucleotide containing AP2, AP1,
      and E2A/MyoD (E box) sites, but not by one containing the POU site. These data
      suggest that the AP2, AP1, and/or E box sites may be involved in forming the cell
      specific complex. Although it lacks an authentic CRE, the 70-bp region also
      mediated a twofold transcriptional response to forskolin, equivalent to that
      found with the endogenous gene. A different region (-60 to -29) bearing a
      consensus CRE mediated a sixfold increase in transcription in response to
      forskolin, but only minimally activated basal transcription from the TH promoter
      in the absence of forskolin.

PMID- 1349343
TI  - Inhibition of tyrosine hydroxylase by R and S enantiomers of salsolinol, 1-methyl
      6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline.
AB  - Salsolinol is one of the dopamine-derived tetrahydroisoquinolines and is
      synthesized from pyruvate or acetaldehyde and dopamine. As it cannot cross the
      blood-brain barrier, salsolinol as the R enantiomer in the brain is considered to
      be synthesized in situ in dopaminergic neurons. Effects of R and S enantiomers of
      salsolinol on kinetic properties of tyrosine hydroxylase [tyrosine,
      tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2], the
      rate-limiting enzyme of catecholamine biosynthesis, were examined. The naturally
      occurring cofactor of tyrosine hydroxylase, L-erythro-5,6,7,8
      tetrahydrobiopterin, was found to induce allostery to the enzyme polymers and to
      change the affinity to the biopterin itself. Using L-erythro-5,6,7,8
      tetrahydrobiopterin, tyrosine hydroxylase recognized the stereochemical
      structures of the salsolinols differently. The asymmetric center of salsolinol at
      C-1 played an important role in changing the affinity to L-tyrosine. The
      allostery of tyrosine hydroxylase toward biopterin cofactors disappeared, and at
      low concentrations of biopterin such as in brain tissue, the affinity to the
      cofactor changed markedly. A new type of inhibition of tyrosine hydroxylase, by
      depleting the allosteric effect of the endogenous biopterin, was found. It is
      suggested that under physiological conditions, such a conformational change may
      alter the regulation of DOPA biosynthesis in the brain.

PMID- 1349344
TI  - Regulation of tyrosine hydroxylase and dopamine beta-hydroxylase mRNA levels in
      rat adrenals by a single and repeated immobilization stress.
AB  - Adrenal catecholamines are known to mediate many of the physiological
      consequences of the "fight or flight" response to stress. However, the mechanisms
      by which the long-term responses to repeated stress are mediated are less well
      understood and possibly involve alterations in gene expression. In this study the
      effects of a single and repeated immobilization stress on mRNA levels of the
      adrenal catecholamine biosynthetic enzymes, tyrosine hydroxylase and dopamine
      beta-hydroxylase, were examined. A repeated 2-hr daily immobilization for 7
      consecutive days markedly elevated both tyrosine hydroxylase and dopamine beta
      hydroxylase mRNA levels (about six- and fourfold, respectively). In contrast,
      tyrosine hydroxylase but not dopamine beta-hydroxylase mRNA levels were elevated
      immediately following a single immobilization. The elevation in tyrosine
      hydroxylase mRNA with a single immobilization was as high as with seven daily
      repeated immobilizations. This elevation was not sustained and returned toward
      control values 24 hr later. Both tyrosine hydroxylase and dopamine beta
      hydroxylase mRNA levels were elevated immediately following two daily
      immobilizations to levels similar to those observed after seven immobilizations
      and were maintained 24 hr later. The results indicate that both tyrosine
      hydroxylase and dopamine beta-hydroxylase mRNA levels are elevated by stress;
      however, the mechanism and/or timing of their regulation are not identical.

PMID- 1349345
TI  - Uptake, metabolism, and release of N-[3H]acetylaspartylglutamate by the avian
      retina.
AB  - N-Acetylaspartylglutamate (NAAG) is a nervous system-specific dipeptide that is
      released from retinal neurons on depolarization. In the present study,
      extracellular metabolism, uptake, and release of [3H]NAAG were examined in the
      chick retina. After in vitro incubation with NAAG radiolabeled in the glutamate
      moiety, [3H]glutamate and [3H]NAAG increased in retinal cells through time- and
      temperature-dependent processes, which were reduced in the absence of
      extracellular sodium. Coincubation of cells with [3H]NAAG and aspartylglutamate
      or phosphate resulted in the decreased extracellular appearance of [3H]glutamate,
      produced by hydrolysis of radiolabeled NAAG, and a consequent increased
      availability of [3H]NAAG for transport into the retinal cells. When this tissue
      was incubated with radiolabeled NAAG, glutamate, glutamine, or aspartate under
      similar conditions, only [3H]NAAG served as a significant source for the
      appearance of intracellular [3H]NAAG. These data support the conclusion that
      [3H]NAAG can be transported into retinal cells, whereas [3H]glutamate transport
      is the predominant process after release of this amino acid from NAAG by
      extracellular peptidase activities. After uptake, [3H]NAAG entered a cellular
      pool, from which the peptide was secreted under depolarizing conditions and in a
      calcium-dependent manner.

PMID- 1349347
TI  - Amperozide, a novel antipsychotic drug, inhibits the ability of d-amphetamine to
      increase dopamine release in vivo in rat striatum and nucleus accumbens.
AB  - The in vivo effects of amperozide, a novel atypical antipsychotic drug, on the
      release of dopamine (DA) and the output of its metabolite, 3,4
      dihydroxyphenylacetic acid (DOPAC), were investigated in the striatum and the
      nucleus accumbens of awake, freely moving rats using microdialysis. Amperozide (2
      10 mg/kg, s.c.) significantly increased extracellular levels of DA in both the
      striatum and nucleus accumbens in a dose-dependent manner. It had a similar but
      lesser effect on extracellular DOPAC levels in both regions. d-Amphetamine (2
      mg/kg, s.c.) alone produced a very large (43-fold) increase in DA release,
      together with a 70% decrease in DOPAC levels in both the striatum and the nucleus
      accumbens. Amperozide (1-5 mg/kg, s.c.) 30 min before d-amphetamine (2 mg/kg)
      dose-dependently attenuated d-amphetamine-induced DA release but had no effect on
      the d-amphetamine-induced decrease in extracellular DOPAC levels in both regions.
      The effect of amperozide on d-amphetamine-induced DA release in the nucleus
      accumbens may explain the inhibitory effect of amperozide on amphetamine-induced
      locomotor activity. However, the failure of amperozide to block amphetamine
      induced stereotypy, despite marked inhibition of striatal DA release, suggests
      the need to reexamine the importance of striatal DA for amphetamine-induced
      stereotypy.

PMID- 1349346
TI  - Amino acid neurotransmitters and dopamine in brain and pituitary of the goldfish:
      involvement in the regulation of gonadotropin secretion.
AB  - An isocratic high-performance liquid chromatographic technique was developed to
      measure levels of gamma-aminobutyric acid (GABA), glutamate, and taurine in the
      brain and pituitary of goldfish. Accuracy of this procedure for quantification of
      these compounds was established by evaluating anesthetic and postmortem effects
      and by selectively manipulating GABA concentrations by intraperitoneal
      administration of the glutamic acid decarboxylase (GAD) inhibitor 3
      mercaptopropionic acid or the GABA transaminase inhibitor gamma-vinyl GABA. The
      technique provided a simple, rapid, and reliable method for evaluating the
      concentrations of these amino acids without the use of complex gradient
      chromatographic systems. To investigate the relationship between neurotransmitter
      amino acids and the control of pituitary secretion of gonadotropin, the effects
      of injection of taurine, GABA, or monosodium glutamate on GABA, glutamate,
      taurine, and, in some instances, monoamine concentrations in the brain and
      pituitary were evaluated and related to serum gonadotropin levels. Injection of
      taurine caused an elevation in serum gonadotropin concentrations. In addition,
      injection of the taurine precursor hypotaurine but not the taurine catabolite
      isethionic acid elevated serum gonadotropin levels. Intracerebroventricular
      injection of either GABA or taurine also elevated serum gonadotropin
      concentrations. Pretreatment of recrudescent fish with alpha-methyl-p-tyrosine
      reduced pituitary dopamine concentrations and also potentiated the serum
      gonadotropin response to taurine. Injection of monosodium glutamate caused an
      increase of glutamate content in the pituitary at 24 h; this was followed by a
      decrease at 72 h after administration. Pituitary GABA, taurine, and dopamine
      concentrations underwent a transient depletion after monosodium glutamate
      administration, and this was associated with an elevation of serum gonadotropin
      content.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349348
TI  - Association of altered RFLP with coeliac disease among Hungarian families.

PMID- 1349349
TI  - Vascular compromise prior to intestinal manifestations of Crohn's disease in a 14
      year-old girl.
AB  - Vascular manifestations as extraintestinal symptoms of Crohn's disease are rare
      and only occasionally reported in children. A 14-year-old girl with vascular
      compromise prior to intestinal manifestations of Crohn's disease is described.
      The vascular symptoms were due to segmental narrowing of several major arteries
      as shown by angiography. This kind of vascular involvement in our patient is
      different from the pattern described in Crohn's disease and resembles Takayasu's
      disease. Recently, it has been suggested that Crohn's disease could be mediated
      by multifocal gastrointestinal infarction due to chronic focal mesenteric
      arteritis at the level of the muscularis propria of the gut. In Takayasu's
      disease, a granulomatous inflammation of the vasa vasorum of affected vessels is
      frequently found. An intramural arteritis, granulomatous in nature, could be the
      common pathway in both Crohn's and Takayasu's diseases. Until the etiologies of
      both diseases are uncovered, the interrelation between them will remain subject
      to speculation.

PMID- 1349350
TI  - Transport of acidic amino acids in Candida albicans.
AB  - In Candida albicans ATCC 10261, two kinetically different amino acid transport
      systems with a high (S1) and a low (S2) affinity for aspartic acid (asp) and
      glutamic acid (glu) were identified. The S1 for the two acidic amino acids was
      characterized by low Kt values while Kt values of S2 were 30 to 40 times higher.
      Based on competitive studies of both systems, S1 was found to be specific and
      common to both asp and glu while S2 was relatively less specific. The S1 and S2
      systems were also different in their sensitivity to respiratory inhibitors,
      mercurials and a K+ channel blocker. Both systems, however, showed maximum
      transport rates during the mid-exponential growth phase.

PMID- 1349352
TI  - Direct photoaffinity labeling of tubulin with taxol.
AB  - BACKGROUND: Taxol is a potent inhibitor of the replication of eukaryotic cells
      and has significant antitumor activity in human malignancies. The drug induces
      the formation of bundles of stable microtubules and blocks cells in the mitotic
      phase of the cell cycle. In vitro, taxol enhances the polymerization of tubulin
      to microtubules that are resistant to depolymerization. Although it is evident
      that taxol interacts with the tubulin-microtubule system, no information has been
      available on the binding site for the drug on the microtubule. PURPOSE: Our
      purpose was to determine if taxol binds to one or both of the tubulin subunits.
      METHODS: In the absence of a photoaffinity-labeled analogue of taxol, [3H]taxol
      was used directly to photolabel tubulin. A complex of microtubule protein and
      [3H]taxol was irradiated by ultraviolet light and analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. RESULTS AND CONCLUSIONS: The
      radiolabeled drug preferentially binds covalently to the beta-subunit of tubulin,
      and the binding can be competed with unlabeled taxol. IMPLICATIONS: This
      observation is the first step in a study to determine the binding site for taxol
      on the microtubule.

PMID- 1349351
TI  - Analogues of the dioxolanes dexoxadrol and etoxadrol as potential phencyclidine
      like agents. Synthesis and structure-activity relationships.
AB  - A series of dioxolane analogues based on dexoxadrol ((4S,6S)-2,2-diphenyl-4-(2
      piperidyl)-1,3-dioxolane) and etoxadrol ((2S,4S,6S)-2-ethyl-2-phenyl-4-(2
      piperidyl)-1,3-dioxolane) were prepared and tested for their ability to displace
      [3H]TCP (1-[1-(2-thienyl)cyclohexyl]piperidine) from PCP (1-(1
      phenylcyclohexyl)piperidine) binding sites in rat brain tissue homogenates.
      Qualitative structure-activity relationships within this series were explored
      through modifications of the three major structural units of dexoxadrol, the
      piperidine, 1,3-dioxolane, and aromatic rings of the molecule. N-Alkyl
      derivatives of dexoxadrol were found to be inactive, as were those analogues
      where the dioxolane ring was modified. Phenyl-substituted etoxadrol analogues
      were compared to similarly substituted PCP analogues and distinct differences
      were found in their structure-activity relationships suggesting that the aromatic
      rings in these two drug classes interact differently with the PCP binding sites.
      The replacement of the phenyl ring in etoxadrol by either a 2- or 3-thienyl ring
      led to compounds with affinity comparable to etoxadrol, and the replacement of
      the ethyl moiety on etoxadrol's dioxolane ring with propyl (7) or isopropyl (8)
      led to compounds which were more potent than etoxadrol or PCP. The most potent
      compound was (2S,4S,6S)-2-ethyl- 2-(1-chlorophenyl)-4-(2-piperidyl)-1,3-dioxolane
      (11), where a chlorine moiety was placed in the ortho position in the aromatic
      ring of etoxadrol. Its potency was comparable with TCP in vitro.

PMID- 1349354
TI  - GnRH-associated peptide (GAP) is present in the rat striatum and affects the
      synthesis and release of dopamine.
AB  - A possible interference of the GnRH-associated peptide (GAP) with the metabolism
      of dopamine in the rat striatum was investigated. The presence of the precursor
      of the peptide in this central region of dopaminergic terminals was first
      evidenced using specific RIA. The action of GAP on dopamine release was
      investigated in the caudate nucleus using the local superfusion with a push-pull
      cannula supplied with an artificial CSF containing the tritiated precursor of
      dopamine [( 3H]tyrosine). Addition of GAP (1 microM) to the superfusing fluid
      resulted in an increase of the release of the newly synthesized dopamine without
      a significant modification of the total amine release. In situ neutralization of
      GAP by addition in the CSF of a rabbit serum containing antibodies directed
      against the GAP produced opposite effects evidencing a tonic function for this
      peptide. In addition to the increased specific activity of the dopamine released
      during GAP treatment, the alterations observed in the efflux (and the specific
      activity) of dihydroxyphenyl acetic acid and the activation of dopamine synthesis
      obtained in vitro in striatal slices in the presence of GAP led us to conclude
      that the GAP system could be considered as a positive control of dopamine
      synthesis.

PMID- 1349353
TI  - Cellular basis for interactions between catecholaminergic afferents and neurons
      containing Leu-enkephalin-like immunoreactivity in rat caudate-putamen nuclei.
AB  - Dopaminergic afferents to the dorsal striatum, caudate-putamen nuclei, are known
      to modulate the levels and synthesis of endogenous opiate peptides (Leu5 and Met5
      enkephalins). We examined the dual immunocytochemical localization of antisera
      raised against Leu5-enkephalin and the catecholamine-synthesizing enzyme,
      tyrosine hydroxylase (TH), to determine the cellular substrates for these and/or
      other functional interactions. The antisera were identified by combined
      immunogold-silver and immunoperoxidase labeling in single coronal sections
      through the caudate-putamen nuclei of adult rats. These animals were given
      intraventricular injections of colchicine, and the brains were fixed by acrolein
      perfusion prior to immunocytochemical labeling. By light microscopy, perikarya
      and processes containing enkephalin-like immunoreactivity (ELI) were seen in
      close proximity to varicose processes immunoreactive for TH. Electron microscopy
      further demonstrated that the ELI was localized to perikarya, dendrites, and axon
      terminals, whereas the TH was exclusively in axons and terminals. The dendrites
      containing ELI were postsynaptic to terminals that were either (1) without
      detectable immunoreactivity, or (2) immunoreactive for TH or enkephalin.
      Nonsynaptic portions of the dendrites containing ELI were covered with astrocytic
      processes or were in direct apposition to unlabeled dendrites. Terminals
      containing ELI were densely immunoreactive and were in direct contact with (1)
      unlabeled and occasionally enkephalin-labeled proximal dendrites, and (2) TH
      labeled and unlabeled terminals. In comparison with the opiate terminals, most
      catecholaminergic terminals were lightly immunoreactive for TH and usually
      contacted more distal unlabeled dendrites or spines and, more rarely, dendrites
      containing ELI. In a few favorable planes of section, the terminals containing
      ELI and those containing TH (1) converged on common unlabeled dendrites, or (2)
      formed dual contacts on two different labeled or unlabeled targets. Junctions
      formed by terminals containing ELI and TH were sometimes characterized by
      symmetric synaptic densities. However, numerous other dendritic and all axonal
      appositions were without recognized membrane densities. The findings of the study
      provide anatomical substrates for multilevel interactions between catecholamines,
      mostly dopamine, and enkephalin in rat dorsal striatum. These include (1)
      monosynaptic input from dopaminergic terminals to neurons containing enkephalin,
      (2) presynaptic modulation of transmitter release through axonal appositions, and
      (3) dual regulation of common targets through convergent input. In addition, the
      findings suggest that both enkephalin and dopamine may have similar modulatory
      roles in synchronizing the activity of dual targets postsynaptic to individual
      axon terminals. Alterations in any one of these multiple types of interactions
      could account for noted motor or sensory symptoms in neurological disorders
      characterized by depletion of dopamine or endogenous opiate peptides, or both.

PMID- 1349355
TI  - From the Food and Drug Administration.

PMID- 1349356
TI  - Effects of H2-receptor antagonists on blood alcohol levels.

PMID- 1349357
TI  - Effects of H2-receptor antagonists on blood alcohol levels.

PMID- 1349358
TI  - Effects of H2-receptor antagonists on blood alcohol levels.

PMID- 1349359
TI  - Effects of H2-receptor antagonists on blood alcohol levels.

PMID- 1349360
TI  - Relationship of human papillomavirus type to grade of cervical intraepithelial
      neoplasia.
AB  - OBJECTIVE--To determine the relationship of human papillomavirus (HPV) type to
      grade of cervical intraepithelial neoplasia (CIN) in a large series of cases.
      DESIGN--A survey of HPV types in CIN lesions detected using a new, highly
      accurate method for typing HPV that is based on restriction fragment length
      polymorphism analysis of amplimers produced during polymerase chain amplification
      of the conserved L1 region of HPV using consensus primers. SETTING--Private
      gynecologists' offices and inner-city colposcopy clinics. PATIENTS--A convenience
      sample of 276 HPV DNA-positive cervical biopsy specimens or samples from patients
      undergoing colposcopy for abnormal Papanicolaou smears. INTERVENTION--None. MAIN
      OUTCOME MEASURE(S)--Human papillomavirus type(s). RESULTS--Cervical
      intraepithelial neoplasia 1 lesions were relatively heterogeneous with regard to
      associated HPV types. Nineteen percent of CIN 1 lesions were associated with HPV
      types 6 or 11; 29% contained HPV types 16, 18, or 33; and 19% were associated
      with "novel types" of HPV. It was also found that 22% of CIN 1 lesions were
      associated with more than one HPV type. In contrast to CIN 1, both CIN 2 and CIN
      3 were relatively homogeneous with regard to associated HPV types. Eighty-eight
      percent of CIN 2 and 3 lesions contained HPV types 16, 18, or 33. Unlike CIN 1
      lesions, which often contained multiple types of HPV, only 7% of CIN 2 and 3
      lesions were associated with multiple HPV types. CONCLUSIONS--Cervical
      intraepithelial neoplasia should be classified into two separate categories--low
      grade and high-grade CIN. Since only 29% of low-grade lesions are associated with
      HPV types 16, 18, or 33, HPV type could potentially play a role in determining
      the most appropriate clinical management of patients with low-grade CIN. However,
      prospective follow-up studies of lesional behavior based on HPV type are required
      before clinical recommendations can be made.

PMID- 1349361
TI  - Prevention of first variceal bleeding: new prospects.

PMID- 1349362
TI  - ISN Forefronts in Nephrology: Mesangial Cells and Extracellular Matrix. Erlangen
      Nurnberg, Germany, June 9-12, 1991.

PMID- 1349363
TI  - Role of intercellular adhesion molecule-1 in the inflammatory response.

PMID- 1349364
TI  - Unstable DNA sequence in myotonic dystrophy.
AB  - A variable DNA sequence has been detected in patients with myotonic dystrophy. We
      set out to determine whether identification of this specific molecular defect
      would improve clinical management of patients and families with myotonic
      dystrophy. 127 affected patients who were studied had an expanded DNA fragment
      not seen in 73 normal controls. The increase in length of the fragment correlated
      broadly with disease severity, and we noted expansion of the sequence in
      successive generations of the same family. Progressive expansion of the affected
      gene provides a molecular explanation for an apparently earlier onset in
      successive generations (anticipation) in myotonic dystrophy and supports the role
      of an unstable repeat sequence as the basis of the defect. The specificity of
      this finding will assist in accurate diagnosis of myotonic dystrophy and genetic
      counselling of affected families.

PMID- 1349365
TI  - Insulin resistance and cigarette smoking.
AB  - Cigarette smoking is associated with increases in plasma triglycerides and
      decreases in plasma high density-lipoprotein-cholesterol concentration. These
      changes not only increase risk of coronary heart disease but also are secondary
      to resistance to insulin-stimulated glucose uptake or hyperinsulinaemia. To see
      whether there is a relation between cigarette smoking and insulin-mediated
      glucose uptake we measured plasma lipid and lipoprotein concentrations, plasma
      glucose and insulin response to an oral glucose challenge, and insulin-mediated
      glucose uptake in 40 matched healthy volunteers (20 non-smokers, 20 smokers).
      Smokers had significantly higher mean (SEM) very-low-density-lipoprotein
      triglycerides (0.66 [0.10] vs 0.39 [0.03] mmol/l, p less than 0.02) and
      cholesterol (0.45 [0.06] vs 0.23 [0.04] mmol/l, p less than 0.005) concentrations
      and lower high-density-lipoprotein cholesterol concentrations (1.16 [0.05] vs
      1.51 [0.08] mmol/l, p less than 0.001). Although plasma glucose concentrations in
      response to the oral glucose load were similar in the two groups, plasma insulin
      response of the smokers was significantly higher (p less than 0.001). Finally,
      smokers had higher steady-state plasma glucose concentrations in response to a
      continuous infusion of glucose, insulin, and somatostatin (8.4 [0.2] vs 5.0 [0.3]
      mmol/l, p less than 0.001), despite similar steady-state plasma insulin
      concentrations. The findings show that chronic cigarette smokers are insulin
      resistant, hyperinsulinaemic, and dyslipidaemic compared with a matched group of
      non-smokers, and may help to explain why smoking increases risk of coronary heart
      disease.

PMID- 1349367
TI  - Betel-nut chewing and asthma.
AB  - Two Asian patients admitted to hospital with acute severe asthma had been chewing
      betel nut immediately before the attacks. Arecoline, a cholinergic alkaloid, is a
      major constituent of Areca catechu (betel) nut and causes the euphoric effects.
      We sought an association between betel-nut chewing and bronchoconstriction in
      asthmatic patients. In vitro, arecoline caused dose-related contraction of human
      bronchial smooth-muscle strips, with one-tenth the potency of methacholine. In a
      double-blind challenge study, inhalation of arecoline caused bronchoconstriction
      in six of seven asthmatic patients and one of six healthy subjects; methacholine
      caused bronchoconstriction in all the asthmatic patients and in five controls.
      The geometric mean concentrations of arecoline and methacholine that caused 20%
      falls in the forced expiratory volume in 1 s (PC20 FEV1) in the asthmatic
      subjects were 5.2 mg/ml and 1.6 mg/ml, respectively. We then studied four Bengali
      asthmatic patients, regular users of betel nut, during a betel-nut challenge.
      Three showed no adverse effects, but one showed a 30% fall in FEV1 by 150 min
      after chewing; the effect was reproducible. In the UK, the rate of hospital
      admission for acute asthma is higher among Asians than among other groups in the
      population; betel-nut chewing may be one of several factors that affect asthma
      control and severity of attacks.

PMID- 1349366
TI  - Effect of vegetarian soy diet on hyperlipidaemia in nephrotic syndrome.
AB  - Nephrotic patients with persistent proteinuria also have various lipid
      abnormalities that may promote atherosclerosis and more rapid progression of
      renal disease. We aimed to find out whether dietary manipulation can correct the
      hyperlipidaemia found in these patients. After a baseline control period of 8
      weeks on their usual diets, 20 untreated patients with chronic glomerular
      diseases, stable long-lasting severe proteinuria (5.9 [SD 3.4] g/24 h) and
      hyperlipidaemia (mean serum cholesterol 8.69 [3.34] mmol/l) ate a vegetarian soy
      diet for 8 weeks. The diet was low in fat (28% of total calories) and protein
      (0.71 [0.36] g/kg ideal body weight daily), cholesterol free, and rich in
      monounsaturated and polyunsaturated fatty acids (polyunsaturated/saturated ratio
      2.5) and in fibre (40 g/day). After the diet period the patients resumed their
      usual diets for 8 weeks (washout period). During the soy-diet period there were
      significant falls in serum cholesterol (total, low-density lipoprotein, and high
      density lipoprotein) and apolipoproteins A and B, but serum triglyceride
      concentrations did not change. Urinary protein excretion fell significantly. The
      concentrations of all lipid fractions and the amount of proteinuria tended to
      return towards baseline values during the washout period. We do not know whether
      the favourable effect of this dietary manipulation on proteinuria was due to the
      qualitative or quantitative modifications of dietary protein intake or was a
      direct consequence of the manipulation of dietary lipid intake.

PMID- 1349368
TI  - Does pralidoxime affect outcome of management in acute organophosphorus
      poisoning?
AB  - Acute organophosphorus (OP) poisoning is usually treated with atropine plus
      cholinesterase reactivators such as oximes, but controlled trials to assess the
      efficacy of oximes in OP poisoning have not been done. A period when the acetyl
      cholinesterase reactivator pralidoxime chloride was not available in Sri Lanka
      gave us the opportunity to compare atropine alone for treatment of moderate to
      severe OP poisoning (21 patients) with atropine plus pralixodime (24 patients).
      Outcome, as assessed clinically, was similar in the two groups. These results
      cast doubt on the necessity of cholinesterase reactivators for treatment of acute
      OP poisoning.

PMID- 1349369
TI  - Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing
      the DiGeorge locus.
AB  - The large clinical overlap between DiGeorge syndrome and velo-cardio-facial
      syndrome suggests an aetiological connection. DiGeorge syndrome is associated
      with microdeletions of chromosome 22q11 and is therefore likely to be caused by
      reduced dosage of genes within this region. We present preliminary data that
      velocardiofacial syndrome patients have similar chromosome deletions, a finding
      consistent with the hypothesis that these disorders represent part of a spectrum
      of abnormalities seen with monosomy for 22q11.

PMID- 1349370
TI  - Viral-associated haemophagocytosis with parvovirus-B19-related pancytopenia.
AB  - Viral-associated haemophagocyte syndrome in response to infection with human
      parvovirus B19 was seen in 2 patients with hereditary spherocytosis. Depressed
      reticulocyte response during acute parvovirus infection is a known cause of
      hypoproliferative crises in patients with reduced erythrocyte lifespan; the
      observation of parvovirus-associated haemophagocytosis could account for the
      pancytopenia that may accompany human parvovirus B19 infection.

PMID- 1349371
TI  - Screening for colorectal cancer by stool DNA analysis.

PMID- 1349372
TI  - Genetics of hypertension.

PMID- 1349373
TI  - Thalamic lesions in infancy.

PMID- 1349374
TI  - Endoprostheses for bony metastases.

PMID- 1349375
TI  - Autosomal dominant polycystic kidney disease. Report of a Meeting of Physicians
      and Scientists, University College and Middlesex School of Medicine, London.

PMID- 1349376
TI  - Controlled trial of hyposensitisation in children with food-induced hyperkinetic
      syndrome.
AB  - Food intolerance seems to be an important cause of the hyperkinetic syndrome, but
      restricted diets are expensive, socially disruptive, and often nutritionally
      inadequate. Enzyme-potentiated desensitisation (EPD) may overcome some of these
      difficulties. EPD was tested in a double-blind placebo-controlled trial among 40
      children with food-induced hyperkinetic behaviour disorder. A total of 185
      children with established hyperkinetic syndrome underwent oligoantigenic dietary
      treatment for four weeks. 116 whose behaviour responded had provoking foods
      identified by sequential reintroduction. Foods that reproducibly provoked
      overactivity were avoided. 40 patients who were then invited to take part in the
      hyposensitisation trial were randomly assigned to treated and control groups.
      Treated patients received three doses of EPD (beta-glucuronidase and small
      quantities of food antigens) intradermally at two-monthly intervals. Controls
      received buffer only. Thereafter, patients were allowed to eat known provoking
      foods. Of 20 patients who received active treatment, 16 became tolerant towards
      provoking foods compared with 4 of 20 who received placebo (p less than 0.001).
      Our results show that EPD permits children with food-induced hyperkinetic
      syndrome to eat foods that had previously been identified as responsible for
      their symptoms. These results also support the notion that food allergy is a
      possible mechanism of the hyperkinetic syndrome.

PMID- 1349377
TI  - Cholesterol inhibition, cancer, and chemotherapy.
AB  - An important feature of malignant transformation is loss of the cholesterol
      feedback inhibition mechanism that regulates cholesterol synthesis. Cancer cells
      seem to require an increase in the concentrations of cholesterol and of
      cholesterol precursors. Therefore, a reasonable assumption is that prevention of
      tumour-cell growth can be achieved by restricting either cholesterol availability
      or cholesterol synthesis. In-vivo and cell-culture experiments have shown that
      lowering the plasma cholesterol concentration or intervening in the mevalonate
      pathway with 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitors decreases
      tumour growth. Currently prescribed doses of HMG-CoA reductase inhibitors given
      orally or continuously by an implantable infusion pump could achieve tumour
      therapeutic tissue concentrations of these agents. My hypothesis is that
      cholesterol inhibition can inhibit tumour cell growth, can act as an adjuvant to
      cancer chemotherapy, and, possibly, can prevent carcinogenesis.

PMID- 1349378
TI  - Diabetes: what sort of prevention?

PMID- 1349379
TI  - Czech and Slovak Federal Republic: not too late to slow HIV-1 spread.

PMID- 1349380
TI  - India: national plan for AIDS control.

PMID- 1349381
TI  - Poland: no sympathy for AIDS patients.

PMID- 1349382
TI  - HIV and breastfeeding.

PMID- 1349383
TI  - Treatable arrhythmias in cardiac arrests seen outside hospital.

PMID- 1349384
TI  - Cholera and the environment.

PMID- 1349385
TI  - HCV genotypes in China.

PMID- 1349386
TI  - Low serum cholesterol and suicide.

PMID- 1349387
TI  - Low serum cholesterol and suicide.

PMID- 1349389
TI  - Prescribing benzodiazepines to drug misusers.

PMID- 1349388
TI  - Low serum cholesterol and suicide.

PMID- 1349390
TI  - Successful in-vitro fertilisation and embryo transfer after treatment with
      recombinant human FSH.

PMID- 1349391
TI  - Successful in-vitro fertilisation and embryo transfer after treatment with
      recombinant human FSH.

PMID- 1349392
TI  - Adenomatous colonic polyps and colon cancer.

PMID- 1349393
TI  - Clinical importance of HCV confirmatory testing in blood donors.

PMID- 1349394
TI  - Magnetic resonance imaging in cobalamin deficiency.

PMID- 1349395
TI  - Grass pollen and asthma.

PMID- 1349396
TI  - Grass pollen and asthma.

PMID- 1349397
TI  - Chlamydia pneumoniae infection and asthma.

PMID- 1349398
TI  - Chlamydia trachomatis infection in children with wheezing simulating asthma.

PMID- 1349399
TI  - Reversal by ceftriaxone of dilated cardiomyopathy Borrelia burgdorferi infection.

PMID- 1349400
TI  - Haemodynamic correction in multiorgan donation.

PMID- 1349401
TI  - Uveitis and antineutrophil cytoplasmic antibody in immunoglobulin batches.

PMID- 1349402
TI  - Rapid test for malaria diagnosis.

PMID- 1349403
TI  - Effect of vegetarian diet on systemic lupus erythematosus.

PMID- 1349404
TI  - Dermatan sulphate in acute leukaemia.

PMID- 1349405
TI  - River blindness.

PMID- 1349406
TI  - Inadequate information on needlestick accidents.

PMID- 1349407
TI  - Amylin concentrations and glucose control.

PMID- 1349408
TI  - Quantitative microscopy and clinically significant bacteriuria.

PMID- 1349410
TI  - Genetic counselling and hereditary breast ovarian cancer.

PMID- 1349409
TI  - Quantitative microscopy and clinically significant bacteriuria.

PMID- 1349411
TI  - Tuberculosis control in Bangladesh.

PMID- 1349412
TI  - Diagnosis of progressive multifocal leucoencephalopathy by PCR detection of JC
      virus from CSF.

PMID- 1349413
TI  - Seasonal incidence of Pneumocystis carinii pneumonia.

PMID- 1349414
TI  - A special irrigation liquid to increase the reliability of laser-induced
      shockwave lithotripsy.
AB  - For the laser-induced shockwave lithotripsy (LISL) the laser-pulses of a Q
      switched Nd:YAG laser produce an optical breakdown in the irrigation liquid
      surrounding the urinary stone. Subsequently high-pressure shockwaves are emitted
      causing stone fragmentation. Since the LISL is an endoscopic technique, problems
      arise from the transmission of the laser pulses through optical fibers. The
      intensity threshold for an optical breakdown in commonly used saline solution
      amounts to 21 GW/cm2, in optical silica fibers, to about 3 GW/cm2. Therefore bare
      fibers cannot be used without being destroyed by a breakdown. So we have
      developed an irrigation liquid by adding small quantities of metal ions to saline
      solution to lower the threshold intensity. The most suitable ion was Fe3+ in a
      concentration of 0.02 mmol/l, which shows a lowering to 5 GW/cm2. In combination
      with a spherically shaped fiber exit the intensities that have to be transmitted
      are below the threshold of the fiber material. Using this irrigation liquid the
      overall reliability of the method could be significantly increased and several
      stone fragmentations can be performed with a single optical fiber.

PMID- 1349415
TI  - Comparison of a pulsed dye laser and electrohydraulic lithotripsy on porcine
      gallbladder and common bile duct in vitro.
AB  - With the advent of minimal access biliary procedures there is a need for a safe
      intracorporal lithotripsy technique that can be used through small flexible
      endoscopes. Currently, the two techniques available are electrohydraulic
      lithotripsy and laser induced shock wave lithotripsy. In this study we compare
      the effect of a 504 nm coumarin pulsed dye laser and electrohydraulic lithotripsy
      on in vitro porcine gallbladder and common bile duct. Electrohydraulic
      lithotripsy at the lowest energy the generator would deliver caused perforation
      of both tissues in only a few pulses when a 1.9-F probe was placed in direct
      contact with the tissue. Energy from a 504 nm coumarin pulsed dye laser delivered
      through a 320-microns fiber placed in light contact with the tissue caused an
      energy-dependent perforation after 50 pulses in from none to 44% of tissues. It
      was also found that there was a higher incidence of perforation in more vascular
      than non-vascular tissue. When the EHL probe and the laser fiber were held 1-2 mm
      from the tissue surface, discharge of each resulted in no perforation. On
      histological examination of the tissues, the perforations were found to be very
      small with laser lithotripsy and considerably larger with the electrohydraulic
      lithotripsy. It was felt that laser lithotripsy in the clinical situation was
      likely to be much safer than electrohydraulic lithotripsy.

PMID- 1349416
TI  - Alpha 2-adrenoceptor antagonists block the stimulant effects of cocaine in mice.
AB  - In the present study we have investigated the effects of the alpha 2-adrenoceptor
      antagonist idazoxan and its 2-ethoxy derivative RX811059 on the locomotor
      activity induced by cocaine in mice. The stimulant effects of cocaine (15 mg/kg
      i.p.) were significantly antagonised by idazoxan (3 mg/kg i.p.) and RX811059 (1
      mg/kg i.p.) and also initially suppressed by idazoxan (1 mg/kg i.p.) and RX811059
      (0.3 mg/kg i.p.). The alpha 2-adrenoceptor antagonists had no effect on
      locomotion when given alone. These results suggest that noradrenergic mechanisms
      may play a role in the stimulant effects of cocaine and that alpha 2-adrenoceptor
      antagonists like idazoxan may be of some benefit in the clinical management of
      cocaine abuse.

PMID- 1349417
TI  - A key role for type 1 pili in enterobacterial communicability.
AB  - Up to 80% of faecal Escherichia coli strains are able to produce type 1 pili.
      These filamentous bacterial surface organelles, which mediate mannose-sensitive
      attachment to mammalian epithelial cells, are also conserved throughout the
      Enterobacteriaceae. As a potential explanation for their prevalence among
      intestinal isolates of enteric bacteria, it has been widely speculated that type
      1 pili are important for adherence to the host's intestinal mucosa. However,
      conclusive evidence for this idea is lacking, and there are reasonable grounds
      for doubting such an effect. Permanent interruption of type 1 piliation in
      previously pil+ E. coli (by directed mutagenesis of pilA, the gene coding for the
      major structural subunit of type 1 pili) does not diminish the density of
      intestinal colonization in individual animals. Rather, as we demonstrate here,
      this lesion results in a dramatic decrease in transmission of E. coli K1 from
      experimentally colonized neonatal rats to their littermates. The enhanced
      communicability associated with type 1 piliation suggests a heretofore
      unrecognized explanation for the prevalence of type 1 pili among intestinal E.
      coli; one that does not necessarily require the direct action of these organelles
      at the intestinal mucosa.

PMID- 1349419
TI  - International Symposium on Diabetes, Vascular Risks, and Gliclazide (Diamicron).
      Washington, DC, June 28, 1991.

PMID- 1349418
TI  - A leptomycin B resistance gene of Schizosaccharomyces pombe encodes a protein
      similar to the mammalian P-glycoproteins.
AB  - Screening for leptomycin B (LMB)-resistant transformants in a gene library
      constructed in Schizosaccharomyces pombe with the chromosomal DNA of an LMB
      resistant mutant of S. pombe and with multicopy plasmid pDB248' as the vector led
      to the isolation of a gene, named pmd1+, encoding a 1362-amino-acid protein. This
      protein showed great similarity in amino acid sequence to the mammalian P
      glycoprotein encoded by the multidrug resistance gene, mdr, and the Saccharomyces
      cerevisiae a-factor transporter encoded by STE6. In addition, computer analyses
      predicted that the protein encoded by pmd1+ formed an intramolecular duplicated
      structure and each of the halves contained six transmembrane regions as well as
      two ATP-binding domains, as observed with the P-glycoproteins and the STE6
      product. Consistent with this was that S. pombe cells containing the pmd1+ gene
      on a multicopy plasmid showed resistance not only to LMB but also to several
      cytotoxic agents. The pmd1 null mutants derived by gene disruption were viable
      and hypersensitive to these agents. All these data suggest that the pmd1+ gene
      encodes a protein that is a structural and functional counterpart of mammalian
      mdr proteins.

PMID- 1349420
TI  - [Mannose-resistant hemagglutination (MRHA), type 1 fimbriae and hemolysin
      production of urinary and fecal Escherichia coli strains].
AB  - The prevalence E.coli bearing Mannose-Resistant Hemagglutinating (MRHA) adhesin,
      Type 1 fimbriae and hemolytic activity was assessed in 103 E.coli strains
      isolated from 43 male and 60 female adult patients with urinary tract infection.
      For comparison 83 faecal E.coli strains were also examined for the same
      properties. MRHA adhesins were present in 58% (60/103) of the urinary strains,
      and 31% (26/83) of the faecal strains of E.coli. All faecal and 95% (98/103) of
      the urinary strains of E.coli expressed Type 1 fimbriae. Hemolytic activity was
      more frequent among urinary strains than among faecal strains (21%, 12%,
      respectively). The presence of MRHA adhesin and hemolytic activity was found
      correlated in 13.5% (14/103) of urinary strains whereas only one (1.2%) strain
      showed these properties together among the faecal isolates.

PMID- 1349421
TI  - Position papers from the Third National Injury Control Conference: Setting the
      National Agenda for Injury Control in the 1990s. Denver, Colorado, April 22-25,
      1991.

PMID- 1349422
TI  - Trisomy and chromosome size changes in hybrid trypanosomes from a genetic cross
      between Trypanosoma brucei rhodesiense and T. b. brucei.
AB  - Further analysis of hybrid clones from an experimental cross of Trypanosoma
      brucei rhodesiense 058 and T. b. brucei 196 shows 2 of the hybrid clones to have
      DNA contents about 1.5 times parental values. This represents over 40,000 kb of
      extra DNA. Comparison of the molecular karyotypes of parental and progeny
      trypanosomes shows that the bulk of the extra DNA constitutes chromosomes greater
      than 1 Mb in size, although a small proportion can be accounted for by an
      increased number of mini-chromosomes. The 2 hybrid clones have 3 alleles at
      several loci for housekeeping genes as shown by RFLP and isoenzyme analysis.
      Trisomy of the chromosome carrying phosphoglycerate kinase and tubulin genes and
      that carrying the phospholipase C gene was demonstrated by analysis of molecular
      karyotypes. These chromosomes appear prone to substantial size alterations
      associated with genetic exchange. Our results for one of the hybrid clones are
      completely consistent with it being triploid and the product of fusion of haploid
      and diploid nuclei.

PMID- 1349423
TI  - An RFLP map of the Plasmodium falciparum genome, recombination rates and favored
      linkage groups in a genetic cross.
AB  - We report a genetic linkage map of the Plasmodium falciparum genome, using the
      inheritance patterns of nearly 90 RFLP markers in a genetic cross. Markers were
      assigned to polymorphic loci on all 14 nuclear chromosomes. Genetic recombination
      between parental markers was detected in each of the progeny, indicating that
      progeny from cross-fertilization events were favored over progeny from self
      fertilization of either parent alone. Inheritance patterns among the markers
      suggested that certain parental linkage groups on chromosomes 2, 3, 12 and 13
      were favored in the cross. Recombination frequencies on five chromosomes
      indicated an approximate map unit size of 15-30 kb per centiMorgan for P.
      falciparum.

PMID- 1349424
TI  - Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral
      sclerosis.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a chronic degenerative
      neurologic disorder characterized by the death of motor neurons in the cerebral
      cortex and spinal cord. Recent studies have suggested that the metabolism of
      glutamate, a potentially neurotoxic amino acid, is abnormal in patients with ALS.
      We hypothesized that the high-affinity glutamate transporter is the site of the
      defect. METHODS: We measured high-affinity, sodium-dependent glutamate transport
      in synaptosomes from neural tissue obtained from 13 patients with ALS, 17
      patients with no neurologic disease, and 27 patients with other neuro
      degenerative diseases (Alzheimer's disease in 15 patients and Huntington's
      disease in 12 patients). The groups were comparable with respect to age and the
      interval between death and autopsy. Synaptosomes were prepared from spinal cord,
      motor cortex, sensory cortex, visual cortex, striatum, and hippocampus. We also
      measured sodium-dependent transport of gamma-aminobutyric acid and phenylalanine
      in the synaptosomal preparations. RESULTS: In patients with ALS, there was a
      marked decrease in the maximal velocity of transport for high-affinity glutamate
      uptake in synaptosomes from spinal cord (-59 percent, P less than 0.001), motor
      cortex (-70 percent, P less than 0.001), and somatosensory cortex (-39 percent, P
      less than 0.05), but not in those from visual cortex, striatum, or hippocampus.
      The affinity of the transporter for glutamate was not altered. No abnormalities
      in glutamate transport were found in synaptosomes from patients with other
      chronic neurodegenerative disorders. The transport of gamma-aminobutyric acid and
      phenylalanine was normal in patients with ALS. CONCLUSIONS: ALS is associated
      with a defect in high-affinity glutamate transport that has disease, region, and
      chemical specificity. Defects in the clearance of extracellular glutamate because
      of a faulty transporter could lead to neurotoxic levels of extracellular
      glutamate and thus be pathogenic in ALS.

PMID- 1349425
TI  - Amyotrophic lateral sclerosis and glutamate--too much of a good thing?

PMID- 1349426
TI  - Cytokines. Poking holes in the network.

PMID- 1349427
TI  - Less science, more policy at Amsterdam AIDS meeting.

PMID- 1349428
TI  - [Coma due to an overdose of valnoctamide].
AB  - We report a 27-year-old man, who became comatose after autopoisoning with a high
      dose of valnoctamide. He was mechanically ventilated for 12 hours and survived
      without serious side effects. Valnoctamide blood levels were monitored in order
      to study the pharmacokinetics of oral overdosing of this drug. Serum half-time
      levels appeared to be approximately 15 hours.

PMID- 1349429
TI  - Better environment.

PMID- 1349431
TI  - . . . of fish and funds in nursing research.

PMID- 1349430
TI  - Amplification of ERBB-2 (HER-2/NEU) oncogene in different neoplasms of patients
      from USSR.
AB  - 203 tumor specimens from 175 patients were studied. Amplification of ERBB-2 was
      detected in 14 out of 63 (22%) cases of breast carcinoma, in 1 out of 23 patients
      with ovarian cancers, in 1 out of 19 cases of colon carcinoma and in 1 out of 27
      patients with thyroid cancer. We failed to find more than one copy of ERBB-2 in
      34 patients with lung cancers, 6 with sarcomas and 3 with melanomas. There was
      tendency toward correlation between ERBB-2 amplification and lymph node
      involvement in patients with breast carcinoma. Thus, the oncogene ERBB-2 is often
      amplified in human tumors, but breast cancer is characterized by an especially
      high frequency of ERBB-2 amplification.

PMID- 1349432
TI  - Drugs update. Undermining ulcers.

PMID- 1349433
TI  - Prostate Cancer: imaging, management, and screening. Proceedings of the Prostate
      Sessions at the First International Congress of the Dutch Urological Association.
      Rotterdam, the Netherlands, October 9-13, 1991.

PMID- 1349435
TI  - Comparative studies of sulpiride and classical neuroleptics on induction of
      catalepsy, locomotor activity, and brain dopamine metabolism in mice.
AB  - The effects of the peripheral administration of sulpiride on the induction of
      catalepsy, the vertical (VMA) and horizontal (HMA) locomotor activities, and on
      the dopamine metabolism in the limbic system, striatum, and nucleus accumbens
      were examined using mice up to 7.5 h after administration of drugs. These effects
      were compared to those of pimozide and haloperidol. Sulpiride (1.25-160 mg/kg,
      IP) clearly induced catalepsy similar to pimozide (0.0625-4 mg/kg, IP) and
      haloperidol (0.0375-0.3 mg/kg, IP). During the induction of catalepsy, the
      intensity was the strongest at 4.5 h after administration and the ED50 value
      showed 11.5 mg/kg at that time. However, a moderate dose of sulpiride at 10-20
      mg/kg did not show the induction of a dose- and time-dependent catalepsy. During
      the locomotor activity, the VMA was significantly inhibited at 1.5 h and 6 h
      after administration of pimozide (0.25 mg/kg, IP) and haloperidol (0.075 mg/kg,
      IP) as compared to the control group, while the HMA was significantly inhibited
      at 1.5 h after administration of sulpiride (40 mg/kg, IP) and pimozide (0.25
      mg/kg, IP). Subsequently, in the dopamine metabolism, sulpiride, pimozide, and
      haloperidol: 1) considerably accelerated the turnover in the dopamine metabolism
      in three distinct brain areas; 2) increased the levels of the DOPAC, HVA, and 3
      MT even 6 h after administration, as well as at 1.5 h after administration; and
      3) decreased the levels of dopamine in the nucleus accumbens at 1.5 h after
      administration. These results indicate that sulpiride displays a mode of action
      different from pimozide and haloperidol with regard to the induction of
      catalepsy, but not with regard to the locomotion and brain dopamine metabolism.

PMID- 1349434
TI  - Differential localization of alpha 2-adrenergic receptor subtypes in brain.
AB  - The pharmacological identification and characterization of subtypes of alpha 2
      adrenergic receptors have been confirmed by molecular biological investigations.
      Using receptor autoradiographic techniques, it has been possible to show regions
      of the brain where alpha 2 agonist binding ([3H]para-aminoclonidine) is
      preferentially labeling the presumed guaninenucleotide-sensitive, high-affinity
      conformations of the alpha 2 receptor. Careful examination of autoradiograms
      generated using the tritiated antagonists yohimbine, idazoxan, and rauwolscine
      also indicates some disparity in the regions occupied by these radiolabeled
      ligands. Inhibition of [3H]rauwolscine binding with the subtype selective
      compounds, ARC-239, or oxymetazoline demonstrates that there are discrete regions
      of the brain where one receptor subtype predominates over the other. These
      studies indicate that previous investigations utilizing the agonist para
      aminoclonidine as the ligand for obtaining labeling of alpha 2 receptors have
      overlooked some regions of binding due to the subtype selectivity of this ligand.
      A more complete localization of alpha 2-adrenergic receptors can be obtained
      using the tritiated antagonist rauwolscine, and the differential distribution of
      at least two subtypes of the alpha 2 receptor can be obtained by selective
      inhibition of this binding.

PMID- 1349436
TI  - Effects of chronic SCH 23390 or acute EEDQ on the discriminative stimulus effects
      of SKF 38393.
AB  - Three groups of rats (n = 8/group) were trained in a two-lever, food-reinforced
      drug discrimination paradigm to discriminate the D1 agonist SKF 38393 (SKF; 8.0
      mg/kg, IP) from saline. After acquisition of the discrimination, the dose
      response function for SKF (2.0-16 mg/kg, IP) was determined using a cumulative
      dosing procedure. In one group, the SKF dose-response function was redetermined 1
      week after a regimen of 0.25 mg/kg of the D1 antagonist SCH 23390 (SCH), IP,
      once/day for 10 days, again 1 week after a second regimen of 0.5 mg/kg SCH, IP,
      twice/day for 10 days, and a third time after a regimen of 1.0 mg/kg SCH, IP,
      twice/day for 21 days. SKF dose-response functions were redetermined in a group
      of control rats after identical injection regimens of saline. In the third group
      of rats, SKF dose-response functions were redetermined 24 h after an injection of
      N-ethoxycarboxyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (irreversible antagonist)
      vehicle; again 24 h after an injection of 3.0 mg/kg; again 48 h after 6.0 mg/kg
      EEDQ; and finally 48 h after two consecutive daily injections of 6.0 mg/kg EEDQ
      (12 mg/kg total). The dose-response function for the percentage of responses that
      occurred on the SKF lever (%DL) shifted significantly to the left following the
      second regimen of SCH; there was no further shift after the third regimen. The
      effects of SKF on response rate were unchanged by SCH administration. Repeated
      administration of saline did not alter the SKF dose-response function for %DL or
      response rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349437
TI  - Potentiation of 2-deoxy-D-glucose antinociception, but not hyperphagia by
      zolantidine, a histamine (H2) receptor antagonist.
AB  - Antagonism of the histamine (H2) receptor reduces antinociception induced by
      naloxone-resistant foot-shock, naloxone-sensitive foot-shock, and morphine with a
      rank-order potency similar to their H2 antagonism. The antimetabolic glucose
      analog 2-deoxy-D-glucose (2DG) produces antinociceptive and hyperphagic responses
      that dissociate from each other and are in part mediated by opioid systems. The
      present study determined the effects of the brain-penetrating H2 receptor
      antagonist zolantidine (ZOL) on 2DG antinociception on the tail-flick and jump
      tests, as well as on 2DG hyperphagia, in rats. ZOL (0.01-1 mg/kg) potentiated the
      antinociceptive responses induced by a moderate (450 mg/kg) dose of 2DG, but had
      lesser effects upon antinociception induced by a lower (100 mg/kg) 2DG dose. ZOL
      itself slightly increased jump thresholds, but not tail-flick latencies.
      Combinations of ZOL and 2DG produced supraadditive antinociception, even though
      ZOL failed to significantly shift the 2DG dose-response curve to the left. In
      contrast, ZOL failed to alter basal intake or 2DG hyperphagia, supporting
      previous evidence implicating the H1 but not the H2 receptor in these effects.
      These results further dissociate the antinociceptive and hyperphagic effects of
      2DG, and also support previous results indicating both pro- and antinociceptive
      roles for H2 receptors.

PMID- 1349438
TI  - Combined effects of diazepam and melatonin in two tests for anxiolytic activity
      in the mouse.
AB  - The effects of behaviorally nonactive doses of melatonin and diazepam were
      investigated in two test models for anxiolytics in mice to see whether mutual
      enhancement could be observed when the two treatments were combined. The test
      models used were the four plates test and the tail suspension test. In the former
      test anxiolytics increase the number of punished crossings and in the latter
      increase the duration of immobility of mice suspended by the tail. In the four
      plates test combined treatment with melatonin (128 and 256 mg/kg IP) and diazepam
      (0.5 mg/kg PO) caused a significant increase in the number of punished crossings,
      whereas each treatment alone was without effect. Similarly, in the tail
      suspension test, a clear increase in the duration of immobility was observed
      after combined treatment (256 mg/kg IP melatonin + 0.5 mg/kg PO diazepam),
      whereas no effects were observed with the individual treatments alone. These
      results suggest that melatonin can enhance the anxiolytic actions of diazepam.

PMID- 1349439
TI  - Memory impairment in schizophrenia: its extent, affiliations and
      neuropsychological character.
AB  - In a sample of 60 schizophrenic patients encompassing all grades of severity and
      chronicity memory impairment was found to be prevalent, often substantial, and
      disproportionate to the overall level of intellectual impairment. The deficits
      were not easily attributable to poor cooperation, attention or motivation; nor
      were they related to neuroleptic or anticholinergic medication. Memory impairment
      was significantly associated with severity and chronicity of illness and also
      with negative symptoms and formal thought disorder. There was evidence from the
      sample as a whole, and from a more detailed examination of five patients with
      relatively isolated deficits, that schizophrenic memory impairment conformed to
      the pattern seen in the classical amnesic syndrome. Additionally, there was
      preliminary evidence for a marked deficit in semantic memory.

PMID- 1349440
TI  - Movement disorders and psychological tests of frontal lobe function in
      schizophrenic patients.
AB  - Neuropsychological tests of frontal lobe functions were undertaken in 46 chronic
      schizophrenic patients who were also rated for movement disorders. Tardive
      dyskinesia was found to have significant associations with most of these
      psychological tests. The possible mechanisms are discussed within the context of
      known neostriatal psychological functions.

PMID- 1349442
TI  - Glucose- and concentration-dependence of vasopressin-induced hormone release by
      mouse pancreatic islets.
AB  - The effects of arginine-vasopressin (AVP) on hormone release by the endocrine
      pancreas have been studied with incubated islets from normal mice. A wide range
      of AVP concentrations (1 pM-100 nM) were tested in the presence of various
      glucose concentrations. AVP did not affect somatostatin release in a glucose-free
      medium but increased it in the presence of all tested glucose concentrations (3
      30 mM). The lowest effective concentration was 1 mM and the effect was not yet
      maximal at 100 nM AVP. AVP markedly increased glucagon release in the absence of
      glucose. Its effect was attenuated but not abolished when glucagon release was
      inhibited by glucose. Surprisingly, the attenuation of the effect of AVP was
      stronger in 3-10 mM than in 15-30 mM glucose. The lowest effective concentration
      was 1 nM and the effect was not yet maximal at 100 nM AVP. AVP was ineffective on
      basal insulin release (0, 3 and 7 mM glucose), but potentiated the effect of 10,
      15 and 30 mM glucose. The lowest effective concentration was 0.1-1 nM AVP and the
      maximal effect was produced by 10-100 nM AVP. The results suggest a direct action
      of AVP on each of the three islet cell types which display a roughly similar
      sensitivity to the peptide. This sensitivity is too low to make islet cells a
      possible target for circulating AVP under physiological conditions. On the other
      hand, the presence of AVP in the pancreas suggests that it might be involved in
      the peptidergic control of islet function.

PMID- 1349441
TI  - Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of
      action and physiological significance.
AB  - The abundant CNS cholesterol and its sulfate derivative serve as precursors of
      different neurosteroids, which bidirectionally modulate neuronal excitability, by
      potentiating or inhibiting function of the GABAA receptors. The regulation of
      GABAA receptors in the CNS by the steroids of central or peripheral origin may
      constitute a vital means of brain-body communication, essential for integrated
      whole organism responses to external stimuli or internal signals. Modulation of
      the brain GABA receptors by neurosteroids may form the basis of a myriad of
      psychophysiological phenomena, such as memory, stress, anxiety, sleep,
      depression, seizures and others. Therefore, the aberrant synthesis of centrally
      active steroids may contribute to defects in neurotransmission, resulting in a
      variety of neural and affective disorders. The biosynthesis of neurosteroids may
      also be altered by diet and certain psychotropic drugs, thereby affecting
      excitation of neurons. Hereditary differences in the level of synthesis and
      catabolism of different neurosteroids may underlie individual variations in CNS
      excitability, contributing to differences in personality traits, including the
      inherited susceptibility to drug addition.

PMID- 1349443
TI  - New considerations in arthritis care. Proceedings of a meeting. Budapest,
      Hungary, July 1, 1991.

PMID- 1349444
TI  - Making sense of NSAID gastropathy and considering the therapeutic options.
AB  - There is increasing recognition that nonsteroidal anti-inflammatory drugs
      (NSAIDs), while quite effective in treating arthritic symptoms, are associated
      with gastrointestinal mucosal damage. Although therapy for patients with NSAID
      induced ulcers or those at high risk of developing them is still a matter of
      debate, the current literature supports the use of misoprostol as the only drug
      effective for the prevention of both NSAID-induced gastric and duodenal
      ulceration. It has also been shown to treat NSAID-induced gastropathy in patients
      continuing their NSAID therapy. In a study of misoprostol (100 or 200 micrograms
      QID) plus NSAID, after three months of continuous therapy, a significantly lower
      frequency of gastric ulcers in the misoprostol-treated group was revealed: 100
      micrograms misoprostol, 5.6%; 200 micrograms misoprostol, 1.4%; placebo, 21.7%. A
      recent three-month, placebo-controlled study established the efficacy of
      misoprostol 200 micrograms QID in the prevention of NSAID-induced duodenal ulcers
      in 429 patients with osteoarthritis (OA), rheumatoid arthritis (RA), or other
      rheumatic disease, who were receiving daily treatment with various NSAIDs. The
      incidence of duodenal ulcer development over three months was 1.0% in patients
      treated with misoprostol versus 6.3% in placebo-treated patients (P = 0.004). The
      same trial also evaluated the efficacy of misoprostol 200 micrograms QID versus
      placebo in preventing NSAID-induced gastric ulcers. The incidence of gastric
      ulcer over the three-month treatment period was 1.5% in patients treated with
      misoprostol versus 9.0% in placebo-treated patients (P = 0.001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1349445
TI  - Ablation of stimulation of a cAMP-responsive promoter in CHO cell lines defective
      in their cAMP-dependent protein kinase system.
AB  - We have studied the requirement for an intact cAMP-dependent protein kinase (PKA)
      system to regulate cAMP-mediated gene transcription in Chinese hamster ovary
      (CHO) cells. Wild-type CHO cells and mutant CHO cell lines selected for their
      resistance to the growth inhibitory effect of 8-Br-cAMP and defective in their
      PKA system were transiently transfected with reporter plasmids containing 2.5 and
      3.0 kb of the 5'-flanking sequence of the rat tyrosine aminotransferase (TAT)
      gene promoter. This segment of DNA contains no CRE-like sequences, yet wild-type
      transfectants exhibited a specific increase in TAT promoter activity following
      growth in medium containing 8-Br-cAMP. In CHO cell lines defective in their PKA,
      the transfected TAT promoter failed to respond to cAMP treatment. We conclude
      that an intact PKA system is necessary for the cAMP-mediated increase in TAT
      promoter activity in CHO cells and that there is no requirement for a CRE to see
      this effect.

PMID- 1349446
TI  - A high frequency of the A30, B18, DR3, DRw52, DQw2 extended haplotype in
      Sardinian celiac disease patients: further evidence that disease susceptibility
      is conferred by DQ A1*0501, B1*0201.
AB  - This study characterizes by serological and molecular methods the HLA class I and
      class II alleles in a group of celiac disease children, their parents and a
      control group of Sardinian descent. We found the DR3-DQw2 haplotype in all
      patients which was, in almost all cases (84%), associated with the HLA-A30, B18,
      DR3, DRw52, DQw2 extended haplotype named "Sardinian haplotype" because of its
      frequency (12-15%) in this Caucasian population. This is the first time that this
      DQw2-linked haplotype has been reported with such a high frequency in CD.
      However, no different distribution of "Sardinian haplotype" was found comparing
      CD patients with 91 haplotyped DQw2-positive controls. This finding indicates
      that the DQw2 antigen in Sardinians is almost always associated with the A30,
      B18, DR3, DRw52, DQw2 extended haplotype. The DQA1 and DQB1 second exon sequence
      analysis of the B18,DR3 and B8,DR3 haplotypes showed the DQA1*0501 and DQB1*0201
      alleles which shared the already published sequences. DPB1 subtyping showed the
      DPB1*0301 allele more frequently (p less than 0.005) in CD patients but this
      difference was no longer significant when patients and controls, both
      heterozygous for the DR3-DQw2 haplotype, were compared. We suggest that the
      divergent HLA extended haplotypes and DP allele associated with CD, described in
      different Caucasian populations, can be explained by the particular DQw2 linkage
      disequilibrium in each population.

PMID- 1349447
TI  - Developments in the drug treatment of schizophrenia.
AB  - Despite its efficacy in many cases, the drug treatment of schizophrenia remains
      problematic. A substantial proportion of patients do not improve, and many others
      suffer from unpleasant side-effects. In this review, Gavin Reynolds describes the
      new approaches to antipsychotic drug development that attempt to address these
      problems, and relates some of these approaches to growing evidence for neuronal
      pathology in the brain in schizophrenia.

PMID- 1349448
TI  - Induction of protective class I MHC-restricted CTL in mice by a recombinant
      influenza vaccine in aluminium hydroxide adjuvant.
AB  - Induction of class I MHC-restricted cytotoxic T lymphocyte (CTL) responses by
      soluble proteins or peptides requires complex adjuvants or carrier systems which
      are not licensed for use with human vaccines. The data presented in this report
      show that vaccination with a highly purified recombinant influenza protein
      antigen in aluminium hydroxide adjuvant, the only adjuvant currently licensed for
      clinical use, elicited class I restricted CTL and protection from lethal
      challenge with H1N1 and H2N2 viruses. The antigen (D protein, SK&F 106160) is
      produced by expression of H1N1 influenza virus-derived cDNA (strain A/PR/8/34) in
      Escherichia coli, and is composed of the first 81 N-terminal amino acids (aa) of
      the non-structural protein 1 (NS1) fused via a nine nucleotide non-viral linker
      sequence to the 157 C-terminal aa of the haemagglutinin 2 subunit (HA2). Previous
      work by Kuwano et al demonstrated that in vitro stimulation of spleen cells from
      influenza virus-primed mice, with a partially purified preparation of the D
      protein, selected for CD8+ CTL clones which facilitated lung clearance of H1N1
      and H2N2 viruses. In the current study, these results were extended by studying
      the responses of mice actively immunized with highly purified D protein in the
      presence or absence of adjuvants. Vaccination of CB6F1 (H-2dxb) mice with D
      protein in aluminum hydroxide or Freund's complete adjuvant generated H1N1 cross
      reactive, H-2d-restricted, CD8+ CTL directed against an immunodominant HA2
      epitope (aa 189-199). D protein without adjuvant did not elicit CTL, regardless
      of the route of injection. However, long-lived (greater than 6 months) splenic
      memory CTL were elicited by boosting mice intraperitoneally (i.p.) with the D
      protein in the absence of adjuvant. In mice injected subcutaneously with D
      protein in aluminium hydroxide at weeks 0 and 3, survival was increased relative
      to controls up to 16 weeks beyond the second vaccination, after which time
      additional boosting was required for protection. Studies in H-2b and H-2k mice
      vaccinated with the D protein showed that induction of CD4+ T-cell or antibody
      responses, in the absence of CD8+ CTL, did not correlate with protection. Passive
      transfer of immune sera from CB6F1 mice was also not protective. This prototype
      H1N1 recombinant subunit vaccine in aluminium adjuvant should directly address
      the feasibility of achieving a protective cell-mediated immune response in human
      influenza.

PMID- 1349449
TI  - Characterization of mutants of the yeast Yarrowia lipolytica defective in acetyl
      coenzyme A synthetase.
AB  - The expression of the glyoxylate cycle enzymes is required for growth of the
      yeast Yarrowia lipolytica on acetate or fatty acids as sole carbon source. Acetyl
      coenzyme A, which is produced by acetyl-coenzyme A synthetase (ACS) from acetate,
      is needed for induction of this expression. Acetate-non-utilizing mutants of this
      yeast were investigated in order to identify mutants which express no or strongly
      reduced activity of this enzyme. Mutations in gene ICL2 exhibited the strongest
      effects on the activity. In icl2 mutants, lack of ACS activity resulted in a non
      induced glyoxylate cycle on acetate; however, induction on fatty acids was not
      affected. Gene ICL2 was identified as the structural gene encoding the monomer of
      ACS. It is shown that a high level of ACS activity is necessary for full
      expression of the glyoxylate cycle enzymes. Mutations in gene ICL1, which encodes
      isocitrate lyase, resulted in overproduction of ACS without any growth on
      acetate. A new gene (GPR1 = glyoxylate pathway regulation) was detected in which
      trans-dominant mutations inhibit expression of ACS and the glyoxylate cycle on
      acetate as carbon source.

PMID- 1349450
TI  - The effect of selective beta 1-blockade on glucose thresholds for release of
      counterregulatory hormones and symptoms in insulin-dependent diabetes mellitus.
AB  - To evaluate the effect of beta 1-blockade (metoprolol) on the plasma glucose
      thresholds initiating counterregulatory hormone responses and symptoms of
      hypoglycemia, we used a modified glucose clamp technique to produce a
      standardized gradual glucose decline from 5.0 to 2.0 mmol/l in nine patients with
      insulin-dependent diabetes mellitus (IDDM) (HbAlc range 6.7-10.3%, duration of
      diabetes 5-18 years, autonomous neuropathy present in three of the patients). The
      responses were studied once with metoprolol and once with placebo, in random
      order. With the beta 1-selective blockade, epinephrine release was triggered at a
      significantly higher (p less than 0.02) plasma glucose level (3.5 mmol/l) than it
      was with placebo (3.0 mmol/l). Metoprolol did not change thresholds for growth
      hormone (3.7/3.5 mmol/l), cortisol (2.9/2.9 mmol/l), glucagon (2.8/2.8 mmol/l) or
      for pancreatic polypeptide (2.8/2.7 mmol/l). The peak responses of epinephrine
      and growth hormone were significantly higher (p less than 0.01) with the beta 1
      blockade. Metoprolol did not change the thresholds for neuroglycopenic and
      autonomic symptoms. Six out of the seven patients who answered yes to having
      hypoglycemia did so at a higher blood glucose with metoprolol than without. In
      our study, the beta 1-selective blockade altered the responses of
      counterregulatory hormones, but it did not change the thresholds for hypoglycemic
      symptoms.

PMID- 1349451
TI  - Colocalization of prion protein and beta protein in the same amyloid plaques in
      patients with Gerstmann-Straussler syndrome.
AB  - We examined paraffin-embedded brain sections from three patients with Creutzfeldt
      Jakob disease (CJD) and four patients with Gerstmann-Straussler syndrome (GSS)
      who also had beta protein deposits in the brains. Immunostaining using anti-prion
      protein (PrP) and anti-beta protein coupled with formic acid pretreatment,
      revealed PrP deposits and beta protein deposits, respectively. In all four GSS
      patients examined, sequential double immunostaining and single immunostaining in
      serial sections or simultaneous double immunofluorescence revealed the
      colocalization of PrP and beta protein in the same amyloid plaques. The plaques
      labeled with both antibodies were designated as beta-PrP plaques. Small kuru
      plaques of less than 15 microns in diameter were rarely found to coexist with
      beta deposits. The percentages of beta-PrP plaques in larger kuru plaques were
      not constant among the four GSS patients. The colocalization patterns of both
      deposits were observed as being roughly of two types as follows: (1) diffuse beta
      protein deposits located around the PrP core; and (2) a beta protein core and PrP
      core simultaneously existing in one amyloid plaque. Under an electron microscope,
      we were able to confirm the presence of both beta protein and PrP in a single
      plaque in four GSS patients older than 60 years old. In contrast, no
      colocalization of either deposits was seen in the amyloid plaque core fractions
      of a young GSS patient who had no beta protein deposits, even at the electron
      microscopic level. Therefore, the colocalization of both proteins in a single
      plaque is believed to be age-related and incidental in GSS patients but suggests
      a similar morphogenesis of both amyloid deposits.

PMID- 1349452
TI  - Somatostatin decreases calcitonin secretion by cultured cells of human medullary
      carcinoma.

PMID- 1349454
TI  - A symposium: The Role of Calcium Antagonists in Hypertension. New York, New York,
      October 11, 1991.

PMID- 1349453
TI  - Optimal heart rate control for patients with chronic atrial fibrillation: are
      pharmacologic choices truly changing?

PMID- 1349455
TI  - Proliferating cell nuclear antigen counts in formalin-fixed paraffin-embedded
      tissue correlate with Ki-67 in fresh tissue.
AB  - Cell proliferation can be studied by a variety of techniques. However, most
      require fresh tissue. To evaluate cell proliferation in formalin-fixed paraffin
      embedded sections, the authors immunohistochemically studied 35 tumors and 11
      samples of normal/hyperplastic tissue with PC10, a monoclonal antibody directed
      against proliferating cell nuclear antigen. Results were compared with those
      obtained with Ki-67 on fresh tissues. There was no significant difference between
      proliferating cell nuclear antigen and Ki-67 counts, which were strongly
      correlated (r = 0.8). Proliferating cell nuclear antigen positivity was easier to
      evaluate because morphology was better preserved in formalin-fixed tissue. The
      authors conclude that PC10 is an alternative to Ki-67 in evaluating cell
      proliferation and has the advantage of reacting with formalin-fixed paraffin
      embedded tissue.

PMID- 1349456
TI  - Frosted branch angiitis associated with cytomegalovirus retinitis.
AB  - We examined three patients with acquired immunodeficiency syndrome who had
      frosted branch angiitis associated with small patches of cytomegalovirus
      retinitis. Each patient had a low CD4-helper T-lymphocyte count and a T
      lymphocyte helper-suppressor ratio of less than 0.1. Treatment with intravenous
      anticytomegalovirus antibiotics caused the vascular sheathing to resolve within
      two weeks in all three patients, but each patient continued to have a smoldering
      retinitis. Retinal biopsy in one of the patients demonstrated virions whose
      morphologic characteristics were consistent with cytomegalovirus on electron
      microscopy and the identity of which was confirmed by immunohistochemistry.
      Although frosted branch angiitis in otherwise healthy patients responds to
      corticosteroids, similar treatment with corticosteroids for frosted branch
      angiitis associated with cytomegalovirus retinitis in patients with AIDS does not
      seem to be indicated. Before corticosteroid treatment is started for a patient
      with the clinical signs and symptoms of frosted branch angiitis, careful medical
      examination of the patient is necessary.

PMID- 1349457
TI  - The debate on treating individuals incompetent for execution.
AB  - The question of whether to provide mental health treatment to prisoners under
      death sentence who have been judged incompetent for execution presents a powerful
      ethical dilemma for mental health professionals. Arguments that favor or oppose
      the provision of treatment are discussed in the context of the nature of the
      disorder to be treated, the type of treatment to be provided, the goals of
      treatment, and the relevant legal standard for determining competency for
      execution. Arguments against treating the incompetent include 1) the need to
      avoid harming those who are treated, 2) the risk that disclosures in therapy will
      be used for assessment purposes, 3) the need for paternalism when sufficient harm
      is necessary, 4) the adverse impact on the clinician, 5) the potential
      undermining of patient and public perceptions of mental health professionals, and
      6) the poor allocation of limited resources. Arguments for treating the
      incompetent include 1) respect for the wishes of the prisoner, 2) the need to
      clarify the values underlying the refusal to treat, 3) the low risk of harm from
      some forms of treatment, and 4) the adverse impact on the milieu stemming from
      failure to treat. The authors conclude that treating incompetent prisoners may
      not violate ethical standards under some circumstances, and that some forms of
      treatment will require the informed consent of the prisoner.

PMID- 1349458
TI  - Randomized, double-blind, crossover, placebo-controlled comparison of propranolol
      and betaxolol in the treatment of neuroleptic-induced akathisia.
AB  - OBJECTIVE: Beta-blocking agents, particularly propranolol, are considered
      effective in the treatment of neuroleptic-induced akathisia, but considerable
      controversy exists about the involved receptor subtype(s). The authors conducted
      a randomized, controlled trial comparing the effects of propranolol and betaxolol
      to determine whether central beta 1-adrenoceptor blockade is sufficient to
      correct neuroleptic-induced akathisia. METHOD: The subjects were 19 patients
      whose neuroleptic-induced akathisia responded to 20 mg/day of propranolol and
      subsequently reemerged during a placebo washout period. They were randomly
      assigned to propranolol (20 or 40 mg/day) or betaxolol (10 or 20 mg/day) and,
      after another placebo period, were switched to the second beta blocker. RESULTS:
      There was no significant difference in the antiakathisia effects of propranolol
      and betaxolol. CONCLUSIONS: The lack of difference between propranolol and
      betaxolol suggests that beta 1-adrenoceptor blockade is sufficient to improve
      neuroleptic-induced akathisia. The results of this explanatory study need
      therapeutic confirmation.

PMID- 1349459
TI  - Changes in chronic nightmares after one session of desensitization or rehearsal
      instructions.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of one session of
      instructions on the frequency of chronic nightmares and on self-rated distress.
      METHOD: Twenty-eight volunteers with chronic nightmares (mean duration = 19
      years) were treated with either one session of desensitization with instructions
      on how to practice this treatment or with one session of instructions to change
      the nightmare and how to rehearse the new version. The authors administered four
      scales of the SCL-90 and the corresponding scales of the Symptom Questionnaire.
      RESULTS: At 7-month follow-up of 23 patients, there was a significant reduction
      in the frequency of nightmares and significant decreases in self-rated
      depression, anxiety, and hostility. There were no significant differences between
      the effects of the two types of treatment. In four patients, whose mean duration
      of nightmares was 23 years, the nightmares ceased. CONCLUSIONS: The results of
      this preliminary study suggests that the instructions given to the patients
      reduced the frequency of their chronic nightmares and decreased their self-rated
      distress.

PMID- 1349460
TI  - Weight gain among schizophrenic patients treated with clozapine.
AB  - A retrospective chart review was used to assess weight changes in 36 chronic
      schizophrenic inpatients who were treated with clozapine after being treated with
      standard neuroleptics. The average weight gain during 6 months of clozapine
      treatment was 16.9 lb; 75.0% of the patients gained at least 10 lb. The results
      confirm previous findings of clozapine-associated weight gain.

PMID- 1349461
TI  - Laterality of torsion in tardive dystonia.

PMID- 1349462
TI  - Knowledge and beliefs about malaria on the Pacific coastal plain of Guatemala.
AB  - Surveys of residents of the Pacific coast of Guatemala revealed a lack of
      knowledge and many misconceptions about the transmission and treatment of
      malaria, which could adversely affect malaria control measures and antimalarial
      therapy. Although mosquitoes are known to play an important role in malaria
      transmission and are thought to become infected by biting individuals with
      malaria, 75% of people interviewed believe that the mosquitoes can also acquire
      infections from contaminated water or by biting snakes and frogs. Furthermore,
      most residents believe that malaria can be acquired in other ways, such as by
      bathing too frequently or by drinking unboiled water. Although self-treatment of
      malaria with oral and injectable drugs purchased at stores and pharmacies is very
      common, less than 10% of the respondents were aware of the correct curative dose
      of chloroquine. Chloroquine injections are preferred to tablets and believed to
      be approximately three times as potent as tablets of the same concentration.
      Nearly two-thirds of the interviewees believed that pregnant and lactating women
      with malaria should avoid the use of chloroquine because it may cause a
      spontaneous abortion or dry up breast milk. Similar surveys of National Malaria
      Service workers and village malaria workers revealed higher levels of knowledge,
      although the village workers had many misconceptions about malaria transmission.
      An educational campaign directed at correcting some of these misconceptions
      should result in more appropriate self-treatment of malaria and greater
      acceptance by residents of personal protection methods and vector control and
      drug treatment programs.

PMID- 1349463
TI  - Chromogranin A immunoreactivity and Grimelius' argyrophilia. A correlative study
      in mammalian endocrine cells.
AB  - Various endocrine cells can be stained by the argyrophil reaction of Grimelius.
      This silver stain has recently been attributed to chromogranin A, an acidic
      glycoprotein, that is present in many endocrine cells. Using serial sections of
      plastic-embedded tissues (adrenal medulla, pancreas, gastric mucosa) various
      endocrine cells were investigated for their content of chromogranin A
      immunoreactivity and for their argyrophilia. The findings in four species (man,
      cattle, pig, guinea pig) showed that chromogranin A immunoreactivity and
      argyrophil stain partly overlap in identical endocrine cells, but do not
      necessarily coincide in the majority of endocrine cells. We found that endocrine
      cells could be positive for chromogranin A and argyrophilia (e.g., aminergic
      endocrine cells); or positive for chromogranin A but negative for argyrophilia
      (e.g., insulin cells of all species; somatostatin cells of cattle and pig); or
      negative for chromogranin A but positive for argyrophilia (e.g., glucagon cells
      of pig and guinea pig); or negative for chromogranin A and argyrophilia (e.g.,
      somatostatin cells of man and guinea pig). Such heterogeneities of the staining
      pattern for chromogranin A and argyrophil silver reaction were also observed in
      individual endocrine cells of a given population (e.g., gastrin cells). Hence,
      although recent dot-blot tests have shown that chromogranin A is an argyrophilic
      substance, in tissue sections chromogranin A immunostaining and Grimelius' silver
      staining did not coincide in various endocrine cells, for unknown reasons.
      Therefore, it is recommended to use both chromogranin A immunohistochemistry and
      the classical Grimelius' silver stain to "mark" that vast majority of endocrine
      cells in tissue sections.

PMID- 1349464
TI  - Anesthetic properties of riluzole (54274 RP), a new inhibitor of glutamate
      neurotransmission.
AB  - It has been suggested that some anesthetic agents could exert their
      hypnotic/anesthetic effects by selectively blocking receptors involved in the
      central excitatory neurotransmission mediated by glutamate. In the present study,
      we analyzed whether riluzole (54274 RP), a novel compound that inhibits both the
      release and some postsynaptic effects of glutamate in some brain structures, has
      anesthetic properties in rats. For this purpose, we investigated whether 1)
      riluzole administered intraperitoneally (ip) at doses ranging from 2.5 to 45
      mg/kg induces loss of righting reflex (LRR); 2) riluzole (2.5 and 5 mg/kg)
      prolongs sleep-times induced by either ketamine (30 or 80 mg/kg ip) or thiopental
      (25 or 35 mg/kg ip); 3) a 5-mg/kg subanesthetic riluzole dose affects the minimum
      alveolar concentration of halothane (MACh). Onset of drug action was defined as
      the period of time from the ip injection to LRR. Sleep-time was considered the
      period of time from LRR to restoration of righting reflex. Riluzole at doses
      greater than 15 mg/kg was able to induce LRR (riluzole dose for which LRR was
      achieved in 50% of the rats [ED50 = 25.6 mg/kg]). A positive correlation was
      found between the dose of riluzole and sleep-time (r = 0.92, P less than 0.001).
      A 5-mg/kg (but not 2.5-mg/kg) riluzole dose significantly prolonged sleep-times
      induced by both ketamine (30 and 80 mg/kg) and thiopental (25 but not 35
      mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349465
TI  - Guanylyl cyclase-linked receptors.

PMID- 1349466
TI  - Does impairment of energy metabolism result in excitotoxic neuronal death in
      neurodegenerative illnesses?
AB  - The etiology of nerve cell death in neuronal degenerative disease is unknown, but
      it has been hypothesized that excitotoxic mechanisms may play a role. Such
      mechanisms may play a role in diseases such as Huntington's disease, Parkinson's
      disease, amyotropic lateral sclerosis, and Alzheimer's disease. In these
      illnesses, the slowly evolving neuronal death is unlikely to be due to a sudden
      release of glutamate, such as occurs in ischemia. One possibility, however, is
      that a defect in mitochondrial energy metabolism could secondarily lead to slow
      excitotoxic neuronal death, by making neurons more vulnerable to endogenous
      glutamate. With reduced oxidative metabolism and partial cell membrane
      depolarization, voltage-dependent N-methyl-D-aspartate (NMDA) receptor ion
      channels would be more easily activated. In addition, several other processes
      involved in buffering intracellular calcium may be impaired. Recent studies in
      experimental animals showed that mitochondrial toxins can result in a pattern of
      neuronal degeneration closely resembling that seen in Huntington's disease, which
      can be blocked with NMDA antagonists. NMDA antagonists also block neuronal
      degeneration induced by 1-methyl-4-phenylpyridium, which has been implicated in
      experimental models of Parkinson's disease. The delayed onset of
      neurodegenerative illnesses could be related to the progressive impairment of
      mitochondrial oxidative phosphorylation, which accompanies normal aging. If
      defective mitochondrial energy metabolism plays a role in cell death in
      neurodegenerative disorders, potential therapeutic strategies would be to use
      excitatory amino acid antagonists or agents to bypass bioenergetic defects.

PMID- 1349467
TI  - Genetic association and linkage analysis of the apolipoprotein CII locus and
      familial Alzheimer's disease.
AB  - We previously reported a genetic association between the 3.5 kb (F) Taq I
      restriction fragment length polymorphism allele of the apolipoprotein CII gene on
      chromosome 19 and familial Alzheimer's disease. Here, we report an additional
      analysis of this association performed on an expanded and better defined data set
      of 23 families with familial Alzheimer's disease. The F allele frequency in
      affected family members in the expanded set was 0.62 +/- 0.06 (mean +/- standard
      error, n = 51 subjects), which differed significantly from a frequency of 0.39 +/
      0.02 (n = 226) for unrelated control subjects (Z = 3.75, p less than 0.0002).
      These results are consistent with our previous findings and suggest an
      association between the F allele of apolipoprotein CII and familial Alzheimer's
      disease. When the apolipoprotein CII locus was tested for linkage to familial
      Alzheimer's disease, LOD scores summed for the complete group of families were
      negative and close linkage was excluded. Close linkage was also excluded for
      early-onset families (mean onset age less than or equal to 60 years), but small
      positive LOD scores were obtained for late-onset kindreds.

PMID- 1349468
TI  - Soluble methane monooxygenase component B gene probe for identification of
      methanotrophs that rapidly degrade trichloroethylene.
AB  - Restriction fragment length polymorphisms, Western blot (immunoblot) analysis,
      and fluorescence-labelled signature probes were used for the characterization of
      methanotrophic bacteria as well as for the identification of methanotrophs which
      contained the soluble methane monooxygenase (MMO) gene and were able to degrade
      trichloroethylene (TCE). The gene encoding a soluble MMO component B protein from
      Methylosinus trichosporium OB3b was cloned. It contained a 2.2-kb EcoRI fragment.
      With this cloned component B gene as probe, methanotroph types I, II, and X and
      environmental and bioreactor samples were screened for the presence of the gene
      encoding soluble MMO. Fragments produced by digestion of DNA with rare cutting
      restriction endonucleases were separated by pulsed-field gel electrophoresis and
      transferred to Zeta-Probe membrane (Bio-Rad) for Southern blot analysis. Samples
      were also analyzed for the presence of soluble MMO by Western blot analysis and
      the ability to degrade TCE. The physiological groups of methanotrophs in each
      sample were determined by hybridizing cells with fluorescence-labelled signature
      probes. Among twelve pure or mixed cultures, DNA fragments of seven methanotrophs
      hybridized with the soluble MMO B gene probe. When grown in media with limited
      copper, all of these bacteria degraded TCE. All of them are type II
      methanotrophs. The soluble MMO component B gene of the type X methanotroph,
      Methylococcus capsulatus Bath, did not hybridize to the M. trichosporium OB3b
      soluble MMO component B gene probe, although M. capsulatus Bath also produces a
      soluble MMO.

PMID- 1349469
TI  - Immunochemical characterization of rat testicular asparagine synthetase.
AB  - We studied immunochemical properties of rat testicular asparagine synthetase.
      Western blot analysis of testis extract with polyclonal antibody raised against
      purified asparagine synthetase revealed an immunoreactive band at 62 kDa. The
      pancreas, brain, thymus, and spleen also showed 62-kDa bands. The intensities of
      these bands were roughly proportional to the specific activities of the enzyme in
      these tissues. The antibody showed some degree of cross-reactivity to asparagine
      synthetases from human, beef, pig, mouse, guinea pig, chicken, and frog, but not
      carp. But the enzyme from human HL-60 cells and lower vertebrates reacted with
      the antibody less strongly than enzyme from rats. The N-terminal amino acid
      sequence of the enzyme, determined by the Edman degradation method, in 10
      recovered residues was identical to that of human asparagine synthetase deduced
      from corresponding cDNA (I.L. Andrulis et al., 1987, Mol. Cell. Biol. 7, 2435
      2443). Immunohistochemical staining of the testis showed the presence of
      asparagine synthetase mainly in Sertoli cells in the seminiferous tubules.

PMID- 1349470
TI  - Purification and characterization of chaperonin 10 from Chromatium vinosum.
AB  - Chromatium vinosum contains a polypeptide that is functionally and structurally
      similar to the Escherichia coli chaperonin 10. The protein has been purified to
      homogeneity by sucrose density gradient centrifugation followed by gel filtration
      using a Bio-Gel A-1.5 m column. The molecular mass of chaperonin 10, as
      determined by gel filtration or nondenaturing polyacrylamide gel electrophoresis,
      is 95 kDa. The oligomer is composed of seven or eight subunits. Comparisons of
      the overall amino acid composition and N-terminal sequences among chaperonin 10
      species from C. vinosum and E. coli reflect a high degree of similarity. A
      physical association between chaperonins 60 and 10 from C. vinosum, in vitro, is
      supported by three experimental approaches. First, the proteins form a stable
      binary complex in sucrose density gradients, gel filtration chromatography, and
      nondenaturing polyacrylamide gel electrophoresis, solely in the presence of ATP
      and Mg2+. Second, chaperonin 10 from C. vinosum binds, selectively, to a
      chaperonin 60-coupled Affi-Gel 10 matrix column. Third, a slight molar excess of
      chaperonin 10 is able to abolish, almost completely, the ATPase in chaperonin 60.
      The rate for ATPase activity of chaperonin 60 from C. vinosum is enhanced when
      supplemented with monovalent cations.

PMID- 1349471
TI  - Screening for undescended testes.

PMID- 1349472
TI  - Primary adenocarcinoma of third and fourth portions of duodenum. Favorable
      prognosis after resection.
AB  - Duodenal adenocarcinoma, a rare malignant lesion, is associated with a poor 5
      year survival. Few series have addressed differences between resectable tumors of
      the proximal and distal duodenum. We reviewed records of 17 consecutive patients
      with adenocarcinoma of the duodenum who underwent resection: 10 had
      adenocarcinoma of the proximal duodenum, and seven had tumors of the distal
      duodenum. Most patients underwent pancreatoduodenectomy. Five patients with
      adenocarcinoma of the distal duodenum underwent segmental resection. No
      perioperative deaths occurred. Six of 10 patients with proximal tumors died of
      metastatic disease. Of the seven patients with tumors of the distal duodenum,
      five are alive without evidence of disease, and two died of unrelated causes. The
      survival of patients with adenocarcinoma of the distal duodenum is surprisingly
      good, and segmental resection is the procedure of choice.

PMID- 1349473
TI  - Serum lipids, hepatic glycerolipid metabolism and peroxisomal fatty acid
      oxidation in rats fed omega-3 and omega-6 fatty acids.
AB  - Rats were fed, for 3 weeks, high-fat (20% w/w) diets containing sunflower-seed
      oil, linseed oil or fish oil. Chow-fed rats were used as a low-fat reference. The
      high-fat diets markedly reduced non-fasting-rat serum triacylglycerol as compared
      with the low-fat reference, and the highest reduction (85%) was observed with the
      fish-oil group, which was significantly lower than that of the other high-fat
      diets. The serum concentration of phospholipids was significantly reduced (30%)
      only in the fish-oil-fed animals, whereas serum non-esterified fatty acids were
      reduced 40-50% by both the fish-oil- and linseed-oil-fed groups. The liver
      content of triacylglycerol showed a 1.7-fold increase with the fish-oil diet and
      2-2.5-fold with the other dietary groups when compared with rats fed a low-fat
      diet, whereas the hepatic content of phospholipids was unchanged. Peroxisomal
      fatty acid oxidation (acyl-CoA oxidase) was 2-fold increased for the rats fed
      fish oil; however this was not significantly higher when comparison was made with
      rats fed the linseed-oil diet. There was no difference in phosphatidate
      hydrolysis (microsomal and cytosolic fractions) among animals fed the various
      diets. Acyl-CoA:diacylglycerol acyltransferase activity was increased by all high
      fat diets, but the fish-oil-diet-fed group showed a significantly lower enzyme
      activity than did rats fed the other high-fat diets. A linear correlation between
      acyl-CoA:diacylglycerol acyltransferase activity and liver triacylglycerol was
      observed, and the microsomal enzyme activity was decreased 40-50% by incubation
      in the presence of eicosapentaenoyl-CoA. CoA derivatives of arachidonic,
      linolenic and linoleic acid had no inhibitory effect when compared with the
      control. These results indicate that dietary fish oil may have greater
      triacylglycerol-lowering effect than other polyunsaturated diets, owing to
      decreased triacylglycerol synthesis caused by inhibition of acyl
      CoA:diacylglycerol acyltransferase. In addition, increased peroxisomal fatty acid
      oxidation and decreased availability of non-esterified fatty acids could also
      contribute by decreasing the amounts of fatty acids as substrates for
      triacylglycerol synthesis and secretion.

PMID- 1349474
TI  - Synergistic action of tiazofurin and difluorodeoxycytidine on differentiation and
      cytotoxicity.
AB  - Tiazofurin (TR), an inhibitor of IMP dehydrogenase, causes remissions and induced
      differentiation in human leukemia through lowering the concentrations of GTP and
      dGTP. A deoxycytidine analog, difluorodeoxycytidine (DFDC), is an anti-tumor
      agent phosphorylated by deoxycytidine kinase, resulting in decreased
      concentration of dCTP, leading to inhibition of DNA synthesis. In HL-60 cells
      DFDC induced differentiation and inhibited proliferation in a dose-dependent
      manner (IC50 = 4 nM); TR provided synergism with DFDC. DFDC inhibited
      proliferation in OVCAR-5 human ovarian carcinoma cells (IC50 = 25 nM) and colony
      formation in PANC-1 human pancreatic carcinoma cells (IC50 = 2 nM) and rat
      hepatoma 3924A cells (IC50 = 22 nM). TR and DFDC are synergistically cytotoxic in
      hepatoma cells and additive in PANC-1 cells. The two drugs together should be
      helpful in treating leukemias and solid tumors in humans.

PMID- 1349475
TI  - Analysis of carrot genes for proliferating cell nuclear antigen homologs with the
      aid of the polymerase chain reaction.
AB  - We designed a polymerase chain reaction-based strategy to obtain information
      about the origin and distribution of a newly discovered proliferating cell
      nuclear antigen (PCNA) homolog. Carrot genomic segments were amplified using
      degenerate primers for two conserved regions of known PCNA homologs. The genes
      encoding the larger PCNA as well as typical PCNA contained introns. Thus, unlike
      processed PCNA pseudogenes in mammals, the larger homolog is not generated
      through reverse transcription of a typical PCNA mRNA. Moreover, introns of the
      larger PCNA homolog were positioned at the characteristic sites in plant PCNA
      genes. Attempts to amplify cDNA for an additional PCNA homolog from mammalian
      cells have been unsuccessful. These results suggest that the larger PCNA homolog
      was generated, presumably through gene duplication, after the divergence of the
      Planta and Animalia.

PMID- 1349476
TI  - Production and characterization of a monoclonal antibody to dopamine D2 receptor:
      comparison with a polyclonal antibody to a different epitope.
AB  - A monoclonal antibody (Mab) that recognizes the rat dopamine D2 receptor (DAR)
      has been generated using DAR specific peptide. The Mab, IgM isotype recognizes
      five proteins (Mr 220, 145, 95, 66 and 47 kDa) in striatal membrane on Western
      blot. Preincubation of Mab with free peptide blocked the labeling of all five
      bands. A polyclonal antibody against peptide from a different region of the DAR,
      reacted with three out of five proteins (220, 66, and 47 kDa) in these membranes.
      The DAR antagonist NAPS-biotinyl binds to a 220 kDa protein in striatal membrane
      on ligand blotts; the labeling can be blocked by the addition of 2 microM
      sulpride. The 220 kDa Mab reactive protein was less in cerebellum and was absent
      in the liver. Neither the Mab nor polyclonal antibody inhibited binding of a DAR
      antagonist, [3H]YM09151-2, to the striatal membranes. These antibodies will
      enable us to study the structure/function and regulation of the synthesis of DAR
      protein.

PMID- 1349477
TI  - Glial cells as a model for the role of cobalamin in the nervous system: impaired
      synthesis of cobalamin coenzymes in cultured human astrocytes following short
      term cobalamin-deprivation.
AB  - The conversion of cyanocobalamin to adenosyl- and methylcobalamin is impaired in
      cobalamin-deficient cultured human glial cells. In contrast cultured human skin
      fibroblasts retained their ability to synthesize coenzyme forms when grown in
      cobalamin-deficient medium. Cells were pre-conditioned by growing in cobalamin
      deficient media for six weeks and then subcultured in medium containing either
      free or transcobalamin II-bound 57Co-cyanocobalamin. Although both coenzyme
      levels were low in cobalamin-deficient glial cells, the decrease in
      methylcobalamin was more marked than that of adenosylcobalamin. Methionine
      synthase and Cb1 reductase activities were markedly decreased in cobalamin
      deficient glial cells but were unchanged in fibroblasts cultured in cobalamin
      deficient medium. Our data suggest that in glial cells, cobalamin coenzyme
      synthesis and function is exquisitely sensitive to short-term cobalamin
      deprivation. Glial cells apparently synthesize and secrete transcobalamin II
      since antibodies directed against the transport protein inhibit the uptake of
      free cobalamin.

PMID- 1349478
TI  - Resistance of CHO cells expressing P-glycoprotein to cyclopropylpyrroloindole
      (CPI) alkylating agents.
AB  - Several new antitumor agents belonging to the class of minor groove binders that
      are able to form covalent bonds with DNA via a cyclopropylpyrroloindole (CPI)
      group are susceptible to a multidrug resistance (MDR) phenotype in Chinese
      hamster ovary (CHO) cells. The multidrug resistant CCHR-C5 cell line was 16-, 23-
      and 13-fold more resistant to the analogs U-73,975, U-77,779 and U-80,244,
      respectively, although its cytotoxic response to the parent compound CC-1065 was
      similar to the response of the drug-sensitive wild-type cells (AuxB1). For a
      sequence of MDR cell lines showing increasing expression of P-glycoprotein (Pgp)
      there were corresponding increments in the level of resistance to U-73,975,
      arguing that Pgp is the key determinant in resistance of the MDR cells to CPI
      agents. MDR cells treated with U-73,975 showed diminished generation of covalent
      adducts on DNA as well as increased resistance to cytotoxicity.

PMID- 1349479
TI  - Stimulation of dopamine D1 receptors by the D2 agonist CV 205-502 in bovine
      retina homogenates.

PMID- 1349480
TI  - HLA antigens in North American patients with Takayasu arteritis.
AB  - OBJECTIVE: To determine the frequency of HLA class I and II antigens in Caucasian
      North American patients with Takayasu arteritis (TA). METHODS: Seventy-three
      class I antigens and 13 class II antigens were examined in 21 Caucasian North
      American patients with TA, and their frequencies were compared with findings in
      243 healthy, untreated controls. HLA typing was performed by
      microlymphocytotoxicity assay. RESULTS: We found no statistically significant
      positive association of TA with DR2, DR4, DQw3, or any of the other class I or
      class II antigens studied. A negative association between TA and DR1 was noted.
      There was no significant association between any of the HLA antigens and the
      severity of the disease or the presence of complications. CONCLUSION: The
      negative association between TA and the DR1 antigen suggests that this antigen
      may be protective against the development of the disease.

PMID- 1349481
TI  - A survey of states' workers' compensation practices for occupational hearing
      loss. Ad Hoc Committee on Worker's Compensation American Speech-Language-Hearing
      Association.

PMID- 1349482
TI  - Dubbo Study of the elderly: hypertension and lipid levels.
AB  - Untreated hypertension in age groups below 60 years has been shown to be
      associated with significant elevations in serum cholesterol and triglyceride
      levels. Drug therapy of hypertension has also been shown to have adverse effects
      on lipoproteins. We have investigated lipid and lipoprotein levels in a community
      based sample of men and women 60 years and older belonging to one of the
      following groupings: (a) normal blood pressure (n = 1075); (b) untreated
      hypertension (n = 329); (c) drug-treated hypertension (n = 880). Serum lipid,
      lipoprotein, apolipoprotein or plasma glucose levels did not vary significantly
      between untreated hypertensives and normotensives of either sex. In a multiple
      regression model controlling for possible influences of age, overweight, alcohol
      and tobacco usage, and presence of coronary heart disease, anti-hypertensive drug
      therapy significantly predicted increased serum triglycerides (P less than 0.001)
      and reduced high density lipoprotein (HDL) cholesterol levels (P less than 0.01)
      in both sexes, reduced apolipoprotein A-I levels in males (P less than 0.001),
      and increased apolipoprotein B (P less than 0.01) and plasma glucose levels (P
      less than 0.001) in females. Adjusted triglycerides were 20% higher and HDL
      cholesterol was 7% lower in the presence of anti-hypertensive drug therapy. These
      effects were partially consistent with the known actions of thiazide diuretics
      and beta-blockers which were used by more than 50% and 40% of subjects,
      respectively.

PMID- 1349483
TI  - The role of cell division in the induction of clonal anergy.
AB  - The interaction of antigen with lymphocyte antigen receptors can result in either
      clonal expansion or unresponsiveness (anergy). In 1970, Bretscher and Cohn
      proposed a two-signal model of lymphocyte activation to explain this paradox:
      antigen receptor occupancy alone could induce unresponsiveness whereas antigen
      receptor occupancy plus a costimulatory signal could induce immunity. Here, Marc
      Jenkins reviews in vitro and in vivo manifestations of clonal anergy and
      evaluates the ability of the two-signal model to explain these phenomena.

PMID- 1349484
TI  - Quality of life in treatment of hypertension. A metaanalysis of clinical trials.
AB  - A metaanalysis was performed to determine the effects on quality of life (QL) in
      hypertension as reported in published clinical trials of antihypertensive drug
      therapy. All studies included compared active treatment to baseline (placebo or
      no treatment) with the patients as their own control and used blinded, randomized
      trials. Change was measured by self and/or interviewer-assisted evaluation,
      standardized psychomotor/cognitive tests, or sleep laboratory observations. After
      an exhaustive literature search (1970 to 1990), nine published trials of 27
      population groups (n = 1620) using 14 drugs from six pharmacological groups met
      selection criteria and were analyzed for five QL constructs: sexual function,
      sleep, psychomotor, general well-being, and mood. Small positive effect size (d)
      improvement with treatment was seen for sleep (d = 0.106), psychomotor (d =
      0.283), general well-being (d = 0.139), and mood (d = 0.167) while no effect
      could be determined for sexual function (d = -0.030) based on 95% confidence
      intervals. Either a comparably small improvement with treatment or no effect was
      seen among various pharmacological drug groups; no negative effect with treatment
      was identified. A larger positive effect could be postulated if the drug choice
      was individualized to the patient rather than randomized as in clinical trial
      methodology. Although none of the drug groups had a clearly superior effect, a
      more frequent positive effect with angiotensin converting enzyme inhibitors and
      beta-blockers was seen for all constructs. Narrower demographics and smaller
      sample sizes may have biased similar positive effects in calcium-channel blockers
      and diuretics.

PMID- 1349485
TI  - An evaluation of self-measured blood pressure in a study with a calcium-channel
      antagonist versus a beta-blocker.
AB  - In recent years self-measurement of blood pressure at home has gained increasing
      importance but there have been only a few studies comparing casual, ambulatory,
      and self-measured blood pressure determinations during a single clinical trial.
      We therefore compared treatment-induced blood pressure-reductions in a double
      blind, placebo-controlled, parallel study design with a single morning dose of
      either 10 mg bisoprolol (n = 26) or 20 mg nitrendipine (n = 27) with casual blood
      pressure readings in the morning before the dose, ambulatory 24-h monitoring, and
      self-recorded measurements in the morning before the dose and in the evening.
      Mean reductions for systolic and diastolic blood pressure after 4 weeks of
      therapy were significantly greater for bisoprolol than for nitrendipine. The
      treatment-induced blood pressure reductions were most pronounced as assessed by
      casual readings but showed good agreement between casual, ambulatory, and self
      measured blood pressure for group comparisons. In some patients, however, marked
      individual differences between the three methods were observed. Correlation
      coefficients between ambulatory and self-measured blood pressure were 0.4 for
      systolic blood pressure (P less than .05) and 0.6 for diastolic blood pressure (P
      less than .0005). Under the conditions of this parallel study design and the
      usual statistical risks, a difference of 5 mm Hg in diastolic blood pressure can
      be detected in 118 patients at the clinic, in 70 patients if ambulatory blood
      pressure is used, or in 56 patients if self-measured blood pressure is used. In
      conclusion, bisoprolol was more effective over 24 h than nitrendipine at the
      doses studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349486
TI  - Efficacy of conventional and sustained-release verapamil in stable angina
      pectoris.
AB  - The efficacy of sustained-release (s.r.) verapamil and conventional verapamil
      were compared in a double blind, crossover study in 20 patients (age 53 +/- SD6
      years) who had stable effort angina and had used betablockers and long acting
      nitrates for at least two weeks. All patients received s.r. verapamil 200 mg
      b.i.d. and conventional verapamil 120 mg t.i.d. in a randomised order for two
      weeks. A symptom limited bicycle exercise test was performed at the end of the
      patients' previous medication period with betablocker plus long acting nitrate
      and at the end of both verapamil treatments in the morning before drug
      administration and three hours thereafter. All the patients improved subjectively
      during both verapamil regimens according to NYHA classification and they had
      fewer anginal attacks. The time to onset of ST-segment depression during exercise
      remained shorter during beta-blockade and long acting nitrates than during both
      verapamil regimens (P less than 0.05). During the peak action three hours after
      drug administration conventional verapamil was most effective at comparable
      workloads (P less than 0.05), whereas the exercise time was slightly prolonged
      with s.r. verapamil before drug administration.

PMID- 1349487
TI  - H1 antagonists in the management of the itch of urticarias.
AB  - This article reviews the effect of H1 antihistamines on the pruritus of
      urticaria, from articles in which their therapeutic effect on chronic idiopathic
      and physical urticaria is assessed. In limited studies available pruritus
      improved concomitantly with wealing by an average of two thirds, though the
      response in individual patients was variable. In some physical urticarias the
      pruritus and wealing showed disproportionate improvement compared to erythema.
      The minimally sedating H1 antihistamines were as effective or more effective than
      classical H1 antihistamines. The dose of antihistamines that totally abolished a
      histamine weal only partly reduced urticarial weals (therefore by inference also
      of the associated pruritus). Additional therapy aimed at pruritogenic mediators
      other than histamine would be expected to improve urticarial pruritus.

PMID- 1349488
TI  - Effect of H1-receptor blockade on anthralin inflammation.
AB  - The effect of terfenadine, an H1-receptor antagonist, on anthralin inflammation
      was studied in 12 subjects. Subjects were randomised to receive terfenadine 60 mg
      or placebo b.d. in a double-blind, cross-over study. Anthralin 5, 10 and 20
      micrograms in 10 microliters chloroform was pipetted onto flexor forearm skin.
      Anthralin inflammatory oedema and erythema were measured using Harpenden calipers
      and a reflectance photometer, 48 h after anthralin application. After a 3-day
      washout period, placebo and terfenadine were restarted and the procedures
      repeated on the opposite arm. Anthralin erythema and oedema increased with dose
      but the dose-response curves showed no significant difference with or without
      terfenadine (p greater than 0.05). This study shows that H1-receptor blockade
      does not inhibit anthralin inflammation.

PMID- 1349489
TI  - DNA hybridization analysis of mycobacterial DNA using the 18-kDa protein gene of
      Mycobacterium leprae.
AB  - DNA hybridization studies using a 611-base pair (bp) probe, encoding the entire
      18-kDa protein of Mycobacterium leprae, demonstrated that M. simiae, M.
      intracellulare, M. kansasii, M. terrae, ADM-2, M. avium, M. scrofulaceum, M.
      gordonae and M. chelonei appear to possess DNA sequences homologous to the 18-kDa
      protein gene of M. leprae. RFLP analysis revealed that the restriction sites in
      the M. leprae 18-kDa gene were not conserved in the putative gene homologs of M.
      simiae and M. intracellulare. The restriction patterns observed with the 611-bp
      probe were useful in differentiating M. intracellulare, M. simiae, and M. leprae
      from each other, as well as in distinguishing strains of M. simiae serovar 1.
      Finally, the presence of homologous sequences in various mycobacteria did not
      affect the specificity of a previously described PCR test for detection of M.
      leprae, based on the M. leprae 18-kDa protein gene.

PMID- 1349490
TI  - Beta-adrenergic blocking agents: their current status.
AB  - Use of beta (beta)-adrenergic blocking agents began in the 1960s and has risen
      dramatically since then. Newer agents offer more actions and fewer side effects.
      Uses for the drugs continue to increase as their safety and efficacy become
      increasingly apparent. beta block, today, has widespread application in
      cardiovascular disease. In addition, these agents are used in the management of
      endocrine disorders, neurologic situations, psychiatric disorders,
      gastrointestinal problems, and sensory disorders. Many new beta blockers are
      still investigational, and some show even greater promise for therapeutic
      applications in the future.

PMID- 1349491
TI  - Dose-response study with high-dose inhaled salmeterol in healthy subjects.
AB  - A double-blind, placebo-controlled, cross-over study in 10 healthy male subjects
      has been carried out to investigate the non-pulmonary effects of single inhaled
      doses of salmeterol 100 micrograms, 200 micrograms and 400 micrograms and
      salbutamol 400 micrograms from a metered-dose inhaler. At all doses tested,
      salmeterol produced statistically significant changes in pulse rate, tremor,
      blood glucose and plasma potassium concentrations, compared with placebo. All
      changes were dosed related. A number of dose-related adverse events including
      tremor, awareness of heart beat and headache were reported after salmeterol
      administration.

PMID- 1349492
TI  - Dose-dependent alpha 1-adrenoceptor antagonist activity of the anti-arrhythmic
      drug, abanoquil (UK-52,046), without reduction in blood pressure in man.
AB  - 1. The dose-dependency of the alpha 1-adrenoceptor antagonist activity of the
      anti-arrhythmic abanoquil (UK-52,046) was investigated in 10 healthy male
      subjects who received serially increasing infusions of phenylephrine before and
      2, 4, 8, 12, 24 and 48 h after single oral doses of abanoquil 0.25, 0.5 and 1 mg
      and placebo in a double-blind randomised manner. 2. The doses of phenylephrine
      required to increase systolic BP by 20 mm Hg (PS20) were calculated using a
      quadratic fit to the individual dose-response curves. 3. Abanoquil 0.25, 0.5 and
      1 mg increased the PS20 in a dose-dependent manner with effects which were
      maximal at 2 to 8 h and lasted for 24 to 48 h (P less than 0.05). Maximal dose
      ratios were: abanoquil 0.25 mg 2.0 +/- 0.9, 0.5 mg 2.4 +/- 1.3, 1 mg 3.4 +/- 1.1.
      4. No change occurred in supine BP but a small increase (P less than 0.01)
      occurred in supine HR 8 h post-dosing (64 +/- 9, 58 +/- 6 beats min-1 for
      abanoquil 1 mg and placebo respectively). 5. Therefore abanoquil 0.25, 0.5 and 1
      mg showed dose-dependent alpha 1-adrenoceptor antagonist activity with no effect
      on supine BP.

PMID- 1349493
TI  - Evaluation of in vivo partial beta 1/beta 2-agonist activity: a dose-ranging
      study with carteolol.
AB  - 1. The aims of this study were to investigate the partial agonist profile of
      carteolol and evaluate methodology for differentiating relative beta 1 and beta 2
      partial agonist activity (PAA) in vivo. 2. Eight normal subjects received single
      oral doses of carteolol 10 mg, 30 mg and 60 mg; nadolol 40 mg; pindolol 30 mg and
      placebo, given in a single-blind, randomised crossover design. 3. beta 1-PAA was
      demonstrated with carteolol by dose-related increases in resting heart rate and
      systolic blood pressure, and a plateau in the dose-response curve for attenuation
      of exercise tachycardia. beta 2-PAA with carteolol was evidenced by a dose
      related increase in resting finger tremor and progressive attenuation of exercise
      induced hyperkalaemia. beta 2-adrenoceptor antagonism was shown by attenuation of
      terbutaline induced hypokalaemic, chronotropic and finger tremor responses. 4.
      Carteolol behaved as a non-selective beta-adrenoceptor antagonist with both beta
      1 and beta 2-PAA components. In the standard clinical dose range of 10-30 mg, its
      in vivo PAA effects were relatively beta 1-selective. Thus at low doses, there
      appeared to be a dissociation between selectivity of antagonist and partial
      agonist activity. 5. Attenuation of exercise hyperkalaemia appears to be a novel
      and sensitive method for the evaluation of beta 2-PAA in vivo.

PMID- 1349495
TI  - Pharmacokinetics of dipipanone after a single oral dose.
AB  - A single oral dose of Diconal (dipipanone HCl 10 mg, cyclizine HCl 30 mg) was
      given to six volunteers. The mean peak plasma dipipanone concentration was 29 ng
      ml-1, the time to peak plasma concentration was 1-2 h, the mean elimination half
      life was 3.5 h and the mean AUC was 156 ng ml-1 min. Less than 1% of the dose was
      excreted in urine unchanged over 24 h.

PMID- 1349494
TI  - Inhibition of histamine-induced nasal obstruction by cetirizine in allergic
      rhinitis.
AB  - This double-blind randomized crossover placebo-controlled study was designed to
      assess objectively the nasal antihistamine effect of cetirizine in patients with
      allergic rhinitis and control subjects. Nasal challenge was performed by
      nebulization of increasing doubling doses of histamine (0; 0.04 to 1.28
      mg/nostril) in six patients with allergic rhinitis and six control subjects on
      cetirizine (2 x 10 mg daily for 3 days) or placebo. Sneezings were counted and
      nasal obstruction was assessed by subjective scoring and by objective measurement
      of nasal airway resistance by posterior rhinomanometry. Histamine induced
      sneezing and a dose-dependent increase in nasal airway resistance and in
      perceived sensation of obstruction. Responses were greater in patients with
      allergic rhinitis compared with controls, although of borderline significance for
      nasal obstruction. Cetirizine totally abolished sneezing and significantly
      reduced increase in nasal airway resistance and perceived sensation of nasal
      obstruction both in normal and rhinitic subjects. Our results demonstrate by an
      objective measurement the nasal antihistamine effect of cetirizine. We propose
      this simple provocation test to assess the time-course of the effect of
      antihistamines and to compare the relative potency of related compounds.

PMID- 1349497
TI  - Pharmacotherapy of dilated cardiomyopathy: current status and future directions.
AB  - The current status and future directions of the pharmacotherapy of dilated
      cardiomyopathy are reviewed. The Japanese multicenter study on the effect of beta
      blockers revealed significant improvement of NYHA functional classification, LV
      end-diastolic dimension, ejection fraction, and exercise tolerance time in
      patients with dilated cardiomyopathy. From our study using normal rabbits,
      metoprolol augmented adenylate cyclase activity without upregulation of the beta
      adrenergic receptor number. Carteolol, a beta-adrenergic blocker with intrinsic
      sympathomimetic action, prevented the development of dilatation and hypertrophy
      of the heart in the chronic stage following murine encephalomyocarditis (EMC)
      viral myocarditis. Metoprolol exerted no such effect. Animal experiments
      indicated that immunosuppressive treatment for inflammatory myocarditis may
      aggravate the clinical course of the disease. However, immunosuppressive
      treatment in acute myocarditis should be reevaluated with the use of newly
      developed antiviral agents. A new synthetic immunoactive peptide FK 565, given
      before or simultaneously with viral inoculation, proved effective in inhibiting
      myocardial virus replication and myocardial damage in murine EMC viral
      myocarditis. Beneficial effects of captopril on survival rate and myocardial
      injury were demonstrated dose dependently in murine EMC viral myocarditis, even
      when the treatment was started around the peak of virus replication, namely, on
      day 4-14 after inoculation. Captopril may be promising for the treatment of acute
      myocarditis, and hopefully for prevention of the progression from myocarditis to
      dilated cardiomyopathy.

PMID- 1349496
TI  - The effect of celiprolol on glomerular filtration rate and renal blood flow in
      patients with chronic renal impairment and healthy volunteers.
AB  - A double-blind, placebo controlled study investigated the effects of celiprolol,
      200 mg daily for 7 days, on glomerular filtration rate (GFR) and estimated renal
      blood flow (ERBF) in eight healthy volunteers and eight patients with chronic
      renal insufficiency. In healthy volunteers the mean difference in GFR was 4.8 ml
      min-1 (95% CI -8.2 to 17.7 ml min-1) and the mean difference in ERBF was 49.8 ml
      min-1 (95% CI -47.5 to 147 ml min-1) after celiprolol. In patients with chronic
      renal insufficiency the mean difference in GFR was -2.1 ml min-1 (95% CI -64.6 to
      65.8 ml min-1). The study had sufficient power to detect a 15% change in GFR for
      normals and 10% for patients, and for ERBF, changes of 14% and 23% were
      detectable. Celiprolol at a dose of 200 mg daily for 7 days can be used in
      patients with chronic renal insufficiency without adversely affecting GFR or
      ERBF.

PMID- 1349498
TI  - [Polyarteritis nodosa in a woman with temporal arteritis].
AB  - A case of a 74-year-old woman, with a histological diagnosis of Transient
      Arteritis two years before and Nodose Polyarteritis, is described. Although the
      coexistance of these two vasculitis in a same patient has been rarely described
      in the literature, we considered that the diagnostic suscpiction of Nodose
      Polyarteritis should be maintained in a patient with Transient Arteritis
      developing multisystemic signs.

PMID- 1349499
TI  - Micro-effects of language on risk perception in drug prescribing behavior.
AB  - The decision to prescribe neuroleptics for the treatment of psychosis involves a
      potentially tragic choice between, on the one hand, a probability of psychosis
      and a probability of side effects, such as tardive dyskinesia, on the other. In
      an experimental paradigm, we examined this decision process. We hypothesized that
      linguistic factors considered irrelevant under classical formulations of
      individual choice behavior would have a significant effect on this decision. All
      subjects were presented with a case vignette involving a potentially psychotic
      patient. Subjects were then asked what probability of tardive dyskinesia they
      would either "accept" or "risk" in order to prevent psychotic decompensation. In
      addition this factor was crossed with a contextual factor that varied the
      patient's age. The effect of "risk" versus "accept" language was evident in
      significantly different patterns of decision making across age groups. The data
      have important implications for clinical decision making, the elicitation of
      informed consent, and the directions that the courts have taken in malpractice
      and patient's rights cases.

PMID- 1349500
TI  - Typing of Listeria monocytogenes by restriction polymorphism of the ribosomal
      ribonucleic acid gene region.
AB  - Ninety four strains of Listeria monocytogenes of different serovars and phagovars
      as well as of varying origins were characterized by ribosomal RNA gene
      restriction polymorphism. After digestion by EcoRI or HindIII, chromosomal DNAs
      were hybridized with a cloned rDNA probe from Bacillus subtilis that included the
      16S rRNA gene. The 94 strains were divided into 14 ribovars according to the
      different hybridization patterns generated by cleavage with EcoRI. Less important
      genomic heterogeneity could be detected when DNAs were digested by HindIII. EcoRI
      ribovars analysis allowed to describe a new typing scheme which did not
      corroborate routine typings such as serotyping and phage typing. It also
      confirmed a new view of this species in exhibiting a clone gathering most human
      strains, as first inferred from multilocus enzyme analysis (Piffaretti et al.,
      22).

PMID- 1349501
TI  - Agonists of cholinergic and noradrenergic receptors facilitate synergistically
      the induction of long-term potentiation in slices of rat visual cortex.
AB  - Acetylcholine (ACh) and noradrenaline (NA) have been shown to facilitate
      experience-dependent modifications of synaptic connectivity during postnatal
      development of the kitten visual cortex. To further investigate the mechanisms of
      this facilitation we studied the effects of these neuromodulators in an in vitro
      model of use-dependent synaptic plasticity. We have chosen long-term potentiation
      (LTP) in rat visual cortex slices because it shares several features with the in
      vivo model. In both cases induction of synaptic modifications requires that
      postsynaptic activation reaches a critical threshold and in both cases changes
      are induced more easily in young animals and when N-methyl-D-aspartate (NMDA)
      receptor-gated conductances are activated. Intracellular recordings were obtained
      from regular spiking cells in supragranular layers of rat visual cortex and LTP
      was induced by tetanic stimulation of the underlying white matter. Both
      cholinergic and noradrenergic agonists raised the probability that tetanic
      stimuli induced LTP and as in vivo they acted synergistically. These effects were
      mediated by agonists of muscarinic and beta-receptors, respectively. The agonists
      of both receptor systems enhanced the depolarizing response to the tetanus and
      increased NMDA receptor-gated conductances during this response. We suggest that
      this mode of action also accounts for the facilitatory effects which ACh and NA
      have on use-dependent synaptic plasticity in the developing visual cortex.

PMID- 1349502
TI  - [Changes in excitatory amino acids and N-methyl-D-aspartate receptors in the
      brain in aged mice].
AB  - By means of chromatography and radioligand binding assay, changes of excitatory
      amino acids (EAA) and N-methyl-D-aspartate(NMDA)receptors in the cerebral cortex
      of aged mice were investigated. It has been demonstrated that the maximal binding
      capacity (Bmax) of NMDA-sensitive 3H-L-glutamic acid (3H-L-Glu) in the cerebral
      cortex of aged mice (14 months) was obviously decreased as compared with that of
      young mice (2 months), but no significant differences in KD values between young
      and aged mice were observed. The content of L-Glu in the cerebral cortex of aged
      mice was reduced 18.7% when compared with that of young mice. However, no change
      in the content of L-aspartic acid was found. Long-term potentiation (LTP) of
      synaptic transmissions in the hippocampus is mediated by NMDA receptors. We also
      confirmed that the slope and amplitude of hippocampal population spikes were
      significantly lower in aged mice than in young mice after induction of LTP by
      tetanus (100 Hz, ls), and persistent time of LTP in aged mice was shorter as
      compared with that in young mice. The results showed that the functions of the
      central EAA neurotransmitter systems are decreased, and such changes may be
      related to the decline of learning and memory capacities in the aged.

PMID- 1349503
TI  - Assay of stanozolol for tumor initiating and promoting activity in two rat liver
      foci bioassays.
AB  - In this study stanozolol, one of the most abused anabolic steroids, was
      investigated for tumor initiating and promoting activity in two rat liver foci
      bioassays, using gamma-glutamyltranspeptidase (GGT) as marker for detection of
      putative preneoplastic foci. Stanozolol, orally administered for 2 weeks, at a
      dose level approximately 400-times larger than the human therapeutic dose, in
      rats initiated with N-nitroso-diethylamine according to the Solt-Farber system
      assay, did not produce any increase in the number and volume of GGT-positive
      liver foci. A 6-week oral treatment with stanozolol (430 ppm in the diet)
      followed by 2 weeks of 2-acetylaminofluorene (AAF) diet (200 ppm), carried out
      according to the Tatematsu assay system to evaluate the initiating activity, did
      not provoke any significant modification of the number and volume of GGT-positive
      foci as compared to the controls. In the rats receiving AAF (200 ppm in the diet
      for 2 weeks) followed by 6 weeks of stanozolol, to evaluate the promoting
      activity, an increase in number and volume of the GGT-positive foci was observed
      at the highest oral dose, but the differences from the corresponding control
      values which resulted were not statistically significant. Taken as a whole the
      results of this study do not provide any substantial evidence of carcinogenic
      activity of stanozolol in rat liver, even when orally administered at high doses.

PMID- 1349504
TI  - Antiproliferative effect of the garlic compound S-allyl cysteine on human
      neuroblastoma cells in vitro.
AB  - A variety of compounds derived from garlic bulbs have been shown in animal
      systems to possess anticancer properties. However, little information is
      available regarding the effectiveness of garlic in the prevention or treatment of
      human cancers. In the current study, we have assessed the ability of S-allyl
      cysteine (SAC), a derivative of aged garlic extract, to affect the proliferation
      and differentiation of LA-N-5 human neuroblastoma cells in vitro. Time-and dose
      dependent inhibition of cell grow was observed in cultures treated with SAC for
      at least 2 days, with a half-maximal response at approximately 600 micrograms/ml.
      SAC treatment was unable to induce differentiation in neuroblastoma cells as
      assessed by morphological, biochemical and molecular markers. In addition, SAC
      was unable to potentiate the effects of retinoic acid and 8-bromo-cyclic AMP,
      agents known to promote differentiation of LA-N-5 cells. Our results indicate
      that SAC can inhibit human neuroblastoma cell growth in vitro. However, the
      apparent inability of this compound to induce differentiation may limit its
      therapeutic potential.

PMID- 1349505
TI  - Homozygosity of the short arm of chromosome 17 in cervical carcinoma.
AB  - We have determined the frequency of heterozygosity of the short arm of chromosome
      17 in 20 cervical tumours using the highly polymorphic probe pYNZ22. Only 25% of
      the tumours were heterozygous at this locus. This is significantly lower than the
      level of 86% heterozygosity for this locus in the general population indicating
      that loss of one allele occurs in cervical cancer. Heterozygosity for a locus on
      the long arm of the same chromosome showed no significant difference between the
      tumours and the general population indicating that genetic loss was confined to
      the short arm of the chromosome. The analysis of premalignant lesions showed 70%
      of patients were heterozygous suggesting that loss of material from the short arm
      of chromosome 17 took place at a late stage in tumour development. This report
      confirms predictions made from previous karyotypic analysis and is the first
      indication of allele loss on the short arm of chromosome 17 in cervical cancer.

PMID- 1349506
TI  - Parkinsonism associated with calcium channel blockers: a prospective follow-up
      study.
AB  - Parkinsonism is a well-known side effect of some calcium channel blockers (CCB).
      Its long-term evolution, however, is unknown. To clarify this issue, we performed
      a prospective follow-up study involving 32 patients diagnosed with CCB-induced
      parkinsonism. After the baseline examination, the CCB were discontinued and
      serial evaluations were carried out according to the same protocol. Despite a
      global improvement, cognitive and mood disturbances subsided slowly, and tremor
      persisted in most patients. After 18 months of CCB withdrawal, 44% of patients
      had depression, 88% had tremor, and 33% still had criteria for diagnosis of
      parkinsonism. During the survey, only three patients were found to be fully
      recovered. The improvement of some clinical symptoms was related to age: Patients
      younger than 73 years recovered better than older patients did. Our data indicate
      that CCB-induced parkinsonism is not the benign condition previously thought, and
      suggest an age-related prognosis of this entity.

PMID- 1349508
TI  - Motor response to repeated dopaminergic stimulation in Parkinson's disease.
AB  - Recent studies giving subcutaneous apomorphine or intravenous levodopa boluses
      have not found clear evidence of behavioral hyposensitivity to repeated
      dopaminergic stimulation in Parkinson's disease (PD). Here we analyze that data,
      and review experimental findings in animal models and our previous experience
      with parkinsonian patients. We conclude that acute tolerance to pulsatile
      stimulation is likely to play a role in the pathophysiology of motor fluctuations
      in PD.

PMID- 1349507
TI  - A survey of tardive dyskinesia in psychiatric inpatients in Japan.
AB  - To investigate the prevalence of tardive dyskinesia (TD) in a group of
      psychiatric patients receiving low doses of antipsychotic drugs, we examined 647
      Japanese inpatients (361 men and 286 women) with a mean age of 49.8 years,
      receiving a mean dose of antipsychotic drugs of 276.8 mg of chlorpromazine
      equivalent. TD was diagnosed according to the criteria of Schooler and Kane with
      the Abnormal Involuntary Movement Scale. The overall prevalence of TD was 22.3%.
      Mild TD was found in 67.4% of TD patients, moderate TD in 29.2%, and severe TD in
      3.5%. The TD patients were older (59.0 years) than those without this condition
      (47.2 years). The prevalence of TD increased with advancing age until the 7th
      decade, when it reached a plateau. The dose of daily antipsychotic drugs was
      lower in the TD patients (207.6 mg) than in the patients without TD (296.6 mg).
      The duration of primary illness was longer in the TD patients (28.9 years) than
      in the patients without TD (20.4 years). Patients receiving antiparkinsonism
      drugs showed TD less frequently (20.7%) than those not receiving such drugs
      (31.0%). No significant associations were found between the presence of TD and
      sex or primary illness.

PMID- 1349509
TI  - Relative efficacy and safety of loratadine, hydroxyzine, and placebo in chronic
      idiopathic urticaria and atopic dermatitis.
AB  - The subjects of this double-blind study were 59 patients with chronic idiopathic
      urticaria or atopic dermatitis randomly assigned to receive 10 mg of loratadine
      once daily and placebo twice daily (n = 20), 25 mg of hydroxyzine thrice daily (n
      = 20), or placebo thrice daily (n = 19). The patients (15 men, 44 women) were
      aged 18 to 65 years. Among the 18 patients with urticaria and 41 with atopic
      dermatitis, daily symptom scores decreased 43% and 57% in those receiving
      loratadine, 47% and 38% in those receiving hydroxyzine, and 0% and 33% in the
      placebo patients. The difference between the treated and placebo patients was
      significant among the urticaria patients. According to a global evaluation of
      treatment effects, more treated than placebo patients reported marked or complete
      symptom relief; among the patients with atopic dermatitis, the difference was
      significant between the loratadine and placebo patients. Somnolence or sedation
      during treatment was reported by one of the patients receiving loratadine, by
      eight of the hydroxyzine patients, and by two of the placebo patients; the
      difference between the loratadine and hydroxyzine patients was significant. It
      was concluded that loratadine is as effective as hydroxyzine in the treatment of
      urticaria and demonstrates a significant antipruritic effect in atopic
      dermatitis, but does not have the central nervous system effects of hydroxyzine.

PMID- 1349510
TI  - Accessory function of human mononuclear phagocytes for lymphocyte responses to
      the superantigen staphylococcal enterotoxin B.
AB  - The role of the cytokines IL-1 alpha, IL-1 beta, and IL-6 and the cell adhesion
      molecules ICAM-1, LFA-1 (alpha and beta), and Mac-1 as accessory molecules for
      stimulation of T cells by the superantigen staphylococcal enterotoxin B (SEB) was
      examined. Both blood monocytes and alveolar macrophages were used as accessory
      cells because these cells differ in patterns of cytokine expression and thus
      potentially in accessory cell function for superantigens. The blastogenic
      response of highly purified T cells to SEB was reconstituted with either
      monocytes or alveolar macrophages. IL-1 secretion was increased comparably in
      monocytes and alveolar macrophages by SEB, but IL-6 was not stimulated by SEB. IL
      1 alpha plus IL-1 beta reconstituted the response of T cells to SEB but required
      the addition of accessory cells. The cell adhesion molecules ICAM-1 and LFA-1 but
      not Mac-1 also functioned as accessory molecules for SEB-induced cluster
      formation and lymphocyte blastogenesis. Thus, not only must this superantigen
      bind to Class II MHC on accessory cells as is well known, but also SEB requires
      at least certain cytokines (IL-1 alpha and IL-1 beta) produced by accessory cells
      and cell adhesion molecules (ICAM-1 and LFA-1) for activation of T lymphocytes.

PMID- 1349511
TI  - Mycophenolic acid inhibits the degranulation of rat peritoneal mast cells.
AB  - The effect of mycophenolic acid (MPA), a potent inhibitor of inosine
      monophosphate dehydrogenase, on the degranulation of rat peritoneal mast cells
      (RMC) was studied. RMC were pretreated for 48 hr with 0.1-10 microM MPA before
      the cells were sensitized with IgE and triggered with specific Ag. The net amount
      of [3H]5-HT released from granules was decreased by 44 and 32% with 1 and 10
      microM MPA treatment, respectively. MPA inhibition of degranulation was
      completely reversed by the addition of 30 microM guanosine to the incubation
      medium. There was no difference in the apparent number or affinity of IgE binding
      sites between control and MPA-treated RMC. MPA pretreatment also had no effect on
      the IgE receptor-mediated production of PGD2 in RMC. These results suggest that
      depletion of intracellular GTP pools by MPA can disrupt the signaling between the
      IgE receptor and the secretory granules and that, under these same conditions,
      the release and metabolism of arachidonic acid are unaffected.

PMID- 1349512
TI  - Synthesis and biological activities of optical isomers of 2-(4-chlorophenyl)-5,6
      dihydro-(1)benzothiepino[5,4-c]pyridazin-3(2H)-o ne 7-oxide.
AB  - Two enantiomers of 2-(4-chlorophenyl)-5,6-dihydro-(1)benzothiepino[5,4-
      c]pyridazin-3(2H)-one 7-oxide ((+/-)-1: Y-23684) were synthesized in high yields
      by asymmetric oxidation of the synthetic precursor (2) using modified Sharpless
      reagent. Among the oxidants tested, cumene hydroperoxide (CHP) gave the highest
      optical and chemical yields, while tert-butyl, tert-amyl, and 1,1,3,3
      tetramethylbutyl hydroperoxides did not show such high enantio-selectivities. The
      absolute configuration of (+)-1 enantiomer synthesized from 2, Ti(O-iso-Pr)4, (-)
      diethyl tartarate, and CHP was determined to be S by X-ray crystallographic
      analysis. Both enantiomers, S-(+)-1 and R-(-)-1, and (+/-)-1 had approximately
      equivalent in vivo activities to antibicuculline test in mice and anticonflict
      test in rats, although S-( + )-1 showed about three times higher affinity to
      benzodiazepine receptor than R-(-)-1 in [3H]diazepam binding assay.

PMID- 1349513
TI  - Association between growth stimulation by phenobarbital and expression of
      cytochromes P450 1A1, 1A2, 2B1/2 and 3A1 in hepatic hyperplastic nodules in male
      F344 rats.
AB  - This study was conducted to examine relationships between phenobarbital (PB)
      treatment, specific cytochrome P450 gene expression patterns and growth rates of
      hepatic hyperplastic nodules. Nodules were induced in 8 week old male F344 rats
      by a Solt-Farber resistance protocol. Six weeks after diethylnitrosamine (DEN)
      initiation, subgroups of rats were either kept on control chow diet or
      transferred to a chow diet containing 0.05% PB, then killed 2 weeks later.
      [3H]Thymidine was delivered continuously via osmotic minipump during the final 3
      days of the experimental to label dividing cells. PB treatment resulted in a 89%
      increase in the number of persistent gamma-glutamyl transpeptidase (GTT) nodules
      per cm2 section, a 278% increase in the area of persistent GGT nodules per cm2
      section, and a 116% increase in the average area per persistent nodule. PB
      increased the number of [3H]thymidine-labeled persistent GGT nodules but did not
      significantly change the labeling index (LI) distribution pattern or the average
      LI. A slight but uniform increase in CYP1A2 expression (relative to surrounding,
      non-nodular tissue) was observed in 50% (23/46) and 59% (60/102) of persistent
      nodules in control and PB-treated animals respectively. In contrast, for nodules
      undergoing remodeling, CYP1A2 expression was elevated in only 9% (2/22) and 0%
      (0/24) in control and PB groups respectively. In the PB group, CYP2B1/2 was
      underexpressed in 53% (54/102) of persistent GGT nodules and in 0% (0/24) of the
      remodeling nodules. Comparing LI among the persistent GGT nodules, those that
      displayed simultaneous increases in CYP1A2 and decreases in CYP2B1/2 had the
      highest LI, and were followed in level by those expressing either increases in
      CYP1A2 or decreases in CYP2B1/2. Nodules that expressed both CYP1A2 and 2B1/2 in
      a manner similar to the surrounding tissue had the lowest LI. Thus, these data
      suggest that expression of specific forms of cytochrome P450 may be an important
      factor in determining other phenotypic characteristics, e.g. rate of cell
      proliferation and GGT expression, within specific nodules.

PMID- 1349514
TI  - The effects of monensin on blood-borne arrest and glycosylation of BL/VL3
      lymphoma cells.
AB  - We have previously shown that inhibitors of N-glycan processing alter both the
      cell surface carbohydrates and the homing properties in lymphoid cells. We have
      now studied the effects of the ionophore monensin (MON) on these parameters.
      Arrest in the spleen of [111In]-labelled BL/VL3 murine T lymphoma cells, injected
      intravenously was clearly reduced if the cells had been cultured for 24 h in the
      presence of monensin (0.1-1.0 microgram ml-1). We have characterized
      glycopeptides from BL/VL3 murine T lymphoma cells. Following labelling with
      tritiated precursors (fucose, mannose, galactose, glucosamine), surface
      glycopeptides from BL/VL3 murine T lymphoma cells, were released by trypsin and
      separated by gel filtration on Bio-Gel P6 and by affinity chromatography on
      immobilized lectins. After treatment with MON, a class of high molecular mass
      glycopeptides was no longer found. There were less complex and more high mannose
      glycans, as a consequence of a reduction of terminal glycosylation (sialylation,
      fucosylation or incorporation of N-acetyl-glucosamine). Similar findings were
      obtained with immunoprecipitated Thy-1 antigen. However, as estimated by flow
      cytometry analysis, the cell surface expression of Thy-1 was not reduced in MON
      treated cells. Taken together our results show that cell surface oligosaccharides
      are modified dramatically, but that at least, certain cell surface antigens are
      present in normal amounts. It is tempting to speculate that changes in
      glycosylation account for the abnormal homing properties of MON-treated cells.

PMID- 1349515
TI  - Electrical field stimulation-mediated relaxation of rabbit middle cerebral
      artery. Evidence of a cholinergic endothelium-dependent component.
AB  - The effects of electrical field stimulation (EFS) of rabbit middle cerebral
      arteries were examined using wire-mounted arterial segments. EFS of segments
      maintained at rest tension caused a tetrodotoxin-sensitive sympathetic
      contraction. In agonist-contracted segments maintained at approximately 60% of
      tissue maximum force, EFS caused a relaxation in two thirds of the preparations.
      Maximum response (mean +/- SEM) was 33 +/- 3.5% of maximal relaxation. The EFS
      relaxation was tetrodotoxin-sensitive but was not blocked by either chronic
      surgical sympathectomy or exposure to guanethidine (5 microM). Electron
      microscopy of chromaffin-fixed arterial sections showed the presence of
      chromaffin-positive large and small vesicles. Within the same sheath of Schwann
      were also a smaller number of nerve profiles containing many small clear
      vesicles. Removal of the vascular endothelium or treatment with atropine (10 nM)
      eliminated the EFS relaxation in approximately 50% of the segments and reduced
      the response in another 35-40%; in the remainder, relaxation was unaffected.
      Combined data for endothelium removal and atropine treatment showed that each
      caused a significant (p less than 0.01) reduction in the EFS relaxation. Atropine
      also significantly reduced EFS relaxation in guanethidine-treated segments. There
      was no reduction in EFS relaxation after procedures that antagonized ATP- or
      substance P-mediated relaxations. These results indicate that EFS of
      precontracted rabbit middle cerebral artery causes a neurogenic nonadrenergic
      relaxation. The neuroeffector mechanism mediating this response has a
      predominantly cholinergic endothelium-dependent component as well as a
      noncholinergic endothelium-independent component.

PMID- 1349516
TI  - Cholinesterases exhibiting aryl acylamidase activity in human amniotic fluid.
AB  - Acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) in human
      amniotic fluid were estimated in the presence of selective inhibitors. Amniotic
      fluid cholinesterases (mixture of acetylcholinesterase and butyrylcholinesterase)
      purified by procainamide-Sepharose affinity chromatography exhibited aryl
      acylamidase activity which was sensitive to serotonin inhibition (a property of
      aryl acylamidases associated with both acetyl- and butyrylcholinesterases) and
      tyramine activation (shown exclusively by aryl acylamidase associated with
      butyrylcholinesterase). Tyramine activation was unaffected in the presence of the
      selective acetylcholinesterase inhibitor BW284C51 whereas it was abolished in the
      presence of the selective butyrylcholinesterase inhibitor ethopropazine,
      suggesting the presence of both types of aryl acylamidases in amniotic fluid, one
      associated with acetylcholinesterase and the other associated with
      butyrylcholinesterase. Butyrylcholinesterase and the associated aryl acylamidase
      activity in the affinity purified enzyme was selectively immunoprecipitated by a
      polyclonal antibody raised against human serum butyrylcholinesterase. Estimation
      of the activity ratio of acetylcholinesterase to butyrylcholinesterase in a few
      samples of amniotic fluid showed that this could vary depending on the
      butyrylcholinesterase arising from contaminating blood in the samples. Gel
      electrophoresis under non-denaturing conditions and enzyme staining showed that
      butyrylcholinesterase band was detectable on the gel in all the samples whereas
      acetylcholinesterase band was below detectable levels in normal samples but
      visible in samples from pregnancies of neural tube defect fetuses. It is
      suggested that the use of selective cholinesterase inhibitors along with gel
      electrophoresis and immunoprecipitation studies may be useful in the assessment
      of cholinesterase activities in human amniotic fluid.

PMID- 1349517
TI  - Clearance of purified human liver gamma-glutamyltransferase after intravenous
      injection in the rat.
AB  - The clearance of gamma-glutamyltransferase was studied by injecting the purified
      human liver enzyme intravenously in the rat. The results show a biphasic
      clearance, with a rapid initial rate of removal. The initial uptake is more rapid
      for neuraminidase-treated GT. Liver accounts for the bulk organ uptake and the
      enzyme is almost exclusively taken up into the parenchymal cells. We suggest that
      the uptake of circulating GT is receptor mediated, most likely by the galactose
      receptor of the parenchymal cells.

PMID- 1349518
TI  - Biochemical investigation of a Brazilian patient with a defect in mitochondrial
      acetoacetylcoenzyme-A thiolase.
AB  - A case report of 3-ketothiolase deficiency due to a defect of mitochondrial
      acetoacetyl-CoA thiolase protein in a Brazilian boy and its biochemical
      investigation is presented. The child had moderate generalized hypotonia, EEG
      alterations and crises of metabolic acidosis following infections. Hypotonia and
      EEG abnormalities disappeared with a low protein diet, and physical and mental
      development are normal. Urinary organic acid excretion was typical of 3
      ketothiolase deficiency, showing consistently high levels of 2-methyl-3
      hydroxybutyric acid and tiglylglycine. Activation of acetoacetyl-CoA thiolase
      activity by potassium (K) ion in cultured fibroblasts was not observed,
      demonstrating the lack of activity of mitochondrial acetoacetyl-CoA thiolase. In
      addition, the signal for the mitochondrial acetoacetyl-CoA thiolase protein was
      undetectable in the immunoblot analysis. In the pulse-chase experiments, the
      signal for mitochondrial acetoacetyl-CoA thiolase was detected after a 1-h pulse
      but not after a 24-h chase. These results indicate that the deficiency was caused
      by an unstable mitochondrial acetoacetyl-CoA thiolase protein.

PMID- 1349519
TI  - Recent advances in clinical toxicology.

PMID- 1349520
TI  - Role of neurohumoral control of the circulation in determining exercise capacity
      in patients with heart failure.
AB  - The weak relationship between left ventricular function and exercise capacity in
      heart failure has stimulated interest in neurohumoral mechanisms as possibly
      contributing to exercise intolerance. Although chronic activation of
      neuroendocrine systems is characteristic of heart failure and is accompanied by
      impaired reflex responsiveness to physiologic stimuli, data from clinical trials
      do not support the hypothesis that the abnormal neurohumoral state is directly
      related to exercise intolerance. Thus, these systems may play an important role
      in the natural history of the disease and its high mortality, but they may not be
      critical to the impaired exercise capacity.

PMID- 1349521
TI  - [The relationship between metastatic phenotype and steady expression of BGC-Ha
      ras oncogene from metastasis cell lines in nude mice (abstract)].
AB  - NIH/3T3 cells transformed by activated BGC-Ha-ras (6.6 kb) with a point mutation
      at codon 12 were able to induce tumor in nude mice with lung metastasis. The
      metastatic phenotype seemed stable in vivo metastasis assay. After two round
      subculture of the successively induced metastasis foci, two cell lines, GCM-1/3T3
      and GCM-2/3T3, were established. In Southern blot analysis it was found that the
      bands from GCM-1/3T3 and GCM-2/3T3 were the same. Based on Southern analysis and
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RPLF), it
      was proved that the activated c-Ha-ras (6.6 kb) existed all along in the genomes
      of the transformed and metastatic culture cells. Amplification and over
      expression of activated c-Ha-ras were shown by DNA and RNA dot blot hybridization
      in transformed and metastatic culture cells. The metastatic phenotype might be
      related to the existence and steady expression of the point mutated ras.

PMID- 1349522
TI  - [Detection of human papillomavirus (HPV) DNA in carcinoma of uterine cervix and
      genital tract diseases in Jiangsu province, China].
AB  - Pst-1 cleaved DNA restriction fragment length polymorphism (RFLP) of biopsy
      samples from 41 patients with squamous cell carcinoma of uterine cervix collected
      in Jiangsu province, China were examined for HPVs by Southern blot hybridization
      using HPV 16 DNA as a probe. 20 of the 41 samples were positive for HPVs when
      hybridized under non-stringent condition. HPV was not detectable in samples
      collected in the same time period from patients with cervical adenocarcinoma (N =
      2), vaginal carcinoma (N = 3), vulval carcinoma (N = 1) and benign cervicitis (N
      = 8). Of the 20 positive samples, 7 (17.1%) had CHPV X1, a new type of NPV
      previously discovered is China, 6 (14.6%) had HPV 16, 4 (9.9%) had HPV 31, and in
      3 (7.2%) the HPV type is as yet undetermined. Our data indicate that HPV 16 and
      CHPV X1 may be more closely related to cancer of the uterine cervix in Jiangsu
      province.

PMID- 1349523
TI  - Organogenesis in Drosophila melanogaster: embryonic salivary gland determination
      is controlled by homeotic and dorsoventral patterning genes.
AB  - We have investigated Drosophila salivary gland determination by examining the
      effects of mutations in pattern forming genes on the salivary gland primordium.
      We find that the anterior-posterior extent of the primordium, a placode of
      columnar epithelial cells derived from parasegment 2, is established by the
      positive action of the homeotic gene Sex combs reduced (Scr). Embryos mutant for
      Scr lack a detectable placode, while ectopic Scr expression leads to the
      formation of ectopic salivary glands. In contrast, the dorsal-ventral extent of
      the placode is regulated negatively. Functions dependent on the decapentaplegic
      product place a dorsal limit on the placode, while dorsal-dependent genes act to
      limit the placode ventrally. We propose a model in which these pattern forming
      genes act early to determine the salivary gland anlage by regulating the
      expression of salivary gland determining genes, which in turn control genes that
      are involved in salivary gland morphogenesis.

PMID- 1349524
TI  - Hyperprolactinemia. Evaluation and management.
AB  - Hyperprolactinemic syndromes are a diverse group of disorders that present in
      widely different age groups. They are common disorders in both men and women and
      require management over a lifetime. The past 20 years have greatly increased our
      knowledge about these disorders and simplified their management. Yet, we have
      made little progress in understanding the origin and dynamics of pituitary tumors
      and their natural histories, and as yet we have been unable to develop effective
      tumoricidal therapy or medication that corrects, at the central axis level,
      neurotransmitter disorders that may produce hyperprolactinemia. Perhaps these
      issues will be the subject of such reviews in the future.

PMID- 1349525
TI  - An investigation of large inhibitors binding to phosphoglycerate kinase and their
      effect on anion activation.
AB  - This study extends, to a series of larger anions, our earlier investigation of
      the interaction of the trypanocidal drug suramin and other small negatively
      charged molecules with yeast phosphoglycerate kinase. 1H-NMR structural studies
      of phosphoglycerate kinase in the presence of varying concentrations of these
      large molecules (designed to mimic, at one end, the anionic charge distribution
      in the substrate 3-phosphoglycerate, while possibly being able to interact across
      the cleft of the enzyme) including inositol 1,4,5-triphosphate, 4-amino-6
      trichloroethenyl-1,3- benzenedisulphonamide, gallic acid and sulphasalazine are
      described. The anion activation and/or inhibition of the enzyme by these
      molecules are also reported. Evidence that binding to the general anion site in
      the 'basic patch' region of the protein may be responsible for either the
      activating or inhibiting effects, while binding at the hydrophobic (catalytic)
      site leads to inhibition only is presented. A reaction scheme which explains
      these observations is given.

PMID- 1349526
TI  - A novel 24-kDa microtubule-associated protein purified from sea urchin eggs.
AB  - Chromatographic fractionation of a crude extract of sea urchin eggs on a
      hydrophobic column enabled us to find a new 24-kDa microtubule-associated protein
      (SU-MAP24) that bound tightly to the column and was eluted under alkaline
      conditions. Biochemical studies using the purified protein showed its direct
      binding to microtubules reconstituted from tubulin purified from starfish sperm
      outer fibers. SU-MAP24 promoted tubulin polymerization in a dose-dependent
      manner. Immunoblotting analysis showed that SU-MAP24 is present in a microtubule
      protein fraction obtained from a crude extract using taxol, and immunostaining of
      paraffin-sectioned metaphase eggs showed its localization in the mitotic
      apparatus. These results show that SU-MAP24 is a newly identified microtubule
      associated protein.

PMID- 1349527
TI  - Polyclonal immunoglobulin therapy protects against cardiac damage in experimental
      coxsackievirus-induced myocarditis.
AB  - Balb/c male mice infected i.p. with 2 x 10(5) plaque forming units (PFU) of
      coxsackievirus B3 (CVB3) develop severe myocarditis 7 days later. Studies were
      performed to determine whether therapy with normal polyclonal immunoglobulin
      would prevent cardiac inflammation. Partially purified immunoglobulin was derived
      from pooled mouse serum by ammonium sulphate precipitation. Infected animals
      given either 100 or 1000 micrograms of this preparation for 2 days prior to
      infection showed greater than 50% reduction in myocarditis compared to control
      animals which were infected and given either phosphate buffered saline, human
      immunoglobulin or monoclonal mouse IgG to an extraneous antigen. Protection did
      not depend upon inhibition of virus infection since cardiac viral titres were
      frequently equivalent in control and immunoglobulin-treated groups.

PMID- 1349528
TI  - Disposition kinetics and concentration-effect relationship of metipranolol in
      patients with cirrhosis and healthy subjects.
AB  - The disposition kinetics and heart rate reducing effect of deacetylmetipranolol
      (DMP), the active form of the beta-adrenoreceptor blocking agent metipranolol
      (MP), administered as a single 40 mg oral dose have been compared in 6 patients
      with cirrhosis and 6 healthy volunteers. The mean maximal DMP concentration was
      significantly higher and the time to reach the peak level shorter in the patients
      compared to the healthy subjects. There was also a significantly higher AUC of
      DMP, a shorter half-life of the rapid phase of the decline in DMP concentrations,
      a smaller central compartment and lower apparent DMP clearance in patients. A
      correlation with the albumin level was observed in cirrhotics for individual
      values of apparent DMP clearance (r = 0.92) and AUC (r = -0.89). The maximal
      reduction in heart rate was recorded in patients at plasma DMP levels which were
      already significantly lower than the peak levels. Median inhibitory
      concentrations (IC50) and maximum possible heart rate reductions (delta HRmax),
      obtained by fitting individual plots of the plasma DMP concentration-effect
      relationship to the inhibitory Emax model in the postdistributional phase of DMP
      disposition were significantly higher in cirrhotics than in healthy subjects. It
      is conjectured that down-regulation of adrenoreceptors due to chronic sympathetic
      activation in hepatic cirrhosis contributes to decreased sensitivity to the
      reduction in heart rate following a single dose of the beta-blocker.

PMID- 1349530
TI  - Hair analysis for detection of beta-blockers in hypertensive patients.

PMID- 1349529
TI  - Polymorphic debrisoquine oxidation and acute neuroleptic-induced adverse effects.

PMID- 1349531
TI  - Membranes of activated CD4+ T cells expressing T cell receptor (TcR) alpha beta
      or TcR gamma delta induce IgE synthesis by human B cells in the presence of
      interleukin-4.
AB  - In the present study it is demonstrated that human B cells can be induced to
      switch to IgE production following a contact-mediated signal provided by
      activated T cell receptor (TcR) gamma delta+, CD4+ and TcR alpha beta+, CD4+ T
      cell clones and interleukin (IL)-4. The signal provided by these T cell clones
      was antigen nonspecific, indicating that the TcR alpha beta/CD3 or TcR gamma
      delta/CD3 complexes were not involved in these T-B cell interactions. Activated
      TcR alpha beta+, CD8+, and TcR gamma delta+, CD4-CD8-, or resting CD4+ T cell
      clones were ineffective. Intact TcR alpha beta+ or TcR gamma delta+, CD4+ T cell
      clones could be replaced by plasma membrane-enriched fractions isolated from
      these activated CD4+ T cell clones. In contrast, membranes isolated from resting
      TcR alpha beta+, CD4+, TcR gamma delta+, CD4+ T cell clones or an Epstein-Barr
      virus (EBV)-transformed B cell line (EBV-LCL) failed to provide the costimulatory
      signal that, in addition to IL-4, is required for induction of IgE synthesis. As
      described for intact CD4+ T cells, CD4+ T cell membranes induced purified surface
      IgM+ B cells to switch to IgG4- and IgE- but not to IgA-producing cells,
      excluding the possibility of a preferential outgrowth of IgG4- and IgE-committed
      B cells. The membrane activity was inhibited by protease or heat treatment.
      Induction of IgE synthesis by B cells co-cultured with both TcR alpha beta+, CD4+
      and TcR gamma delta+, CD4+ T cell clones and membrane preparations of these cells
      was blocked by anti-class II major histocompatibility complex (MHC) monoclonal
      antibodies (mAb), whereas various anti-CD4 mAb had differential blocking effects.
      Murine L cells, or EBV-LCL transfected with CD4 could not replace CD4+ T cell
      clones. These results indicate that, although CD4 and class II MHC antigens are
      required for productive CD4+ T cell clone-B cell interactions, an additional
      signal, provided by a membrane associated (glyco)protein that is induced by
      activation of both TcR alpha beta and TcR gamma delta, CD4+ T cells, is needed
      for induction of IgE production in the presence of IL-4.

PMID- 1349532
TI  - Molecular cloning of a novel member of the immunoglobulin gene superfamily
      homologous to the polymeric immunoglobulin receptor.
AB  - The CMRF35 monoclonal antibody recognizes a cell membrane antigen present on the
      surface of monocytes, neutrophils, a proportion of peripheral blood T and B
      lymphocytes and lymphocytic cell lines. Initial studies with CMRF35 suggested an
      unusual pattern of serological reactivity which did not correspond to any of the
      known leukocyte differentiation antigen clusters. We describe here the cloning
      and sequencing of a cDNA encoding the CMRF35 antigen by means of expression in
      COS cells and immunoselection with the CMRF35 monoclonal antibody. The cDNA
      encodes a novel integral membrane glycoprotein of 224 amino acids that represents
      a new member of the immunoglobulin (Ig) gene superfamily. The molecule comprises
      (a) a single extracellular Ig variable domain remarkably similar to the Fc
      receptor for polymeric IgA and IgM, (b) a membrane-proximal domain containing a
      high proportion of proline, serine and threonine residues that was predicted to
      be heavily O-glycosylated, (c) an unusual transmembrane anchor that contained a
      glutamic acid and a proline residue and (d) a short cytoplasmic tail. Transcripts
      encoding the CMRF35 protein were detected in early monocytic cell lines, in
      peripheral blood T cells and in some B lymphoblastoid cell lines, confirming the
      results of immunocytological staining. However, the level of CMRF35 expression on
      peripheral blood T cells was shown to decrease in response to mitogenic
      stimulation. The likelihood that the CMRF35 antigen shares a common evolutionary
      ancestor with the poly Ig Fc receptor is discussed.

PMID- 1349533
TI  - Interleukin (IL)-4 production by human T cells: differential regulation of IL-4
      vs. IL-2 production.
AB  - We have examined the regulation of interleukin (IL)-4 production by human
      peripheral blood T cells. Production of IL-4 was shown to be regulated
      differently from IL-2 and interferon(IFN)-gamma production. Stimulation of
      peripheral blood lymphocytes with anti-CD3, anti-CD2, anti-CD28, Phorbol 12
      myristate 13-acetate (PMA) or IL-2 as a single stimulant did not induce IL-4
      production. However, combinations of anti-CD2 with either anti-CD28 or IL-2
      resulted in IL-4 production, peaking at days 3-4. Stimulation with anti-CD3
      instead of anti-CD2 gave similar results, but was less potent. After days 3-4, IL
      4 levels decreased, most likely due to consumption of IL-4. PMA profoundly
      affected cytokine production, it enhanced IL-2 production by at least tenfold,
      whereas, in the same cell population, IL-4 production was almost completely
      inhibited. This was observed at the protein as well as at the mRNA level. In
      contrast, agents that increase intracellular cAMP levels inhibited IL-2
      production but left IL-4 production unaffected. IFN-gamma production behaved
      similar to IL-2 production but the effects were less outspoken.

PMID- 1349534
TI  - Diversity of T cell receptor alpha and beta chain genes expressed by human T
      cells specific for similar myelin basic protein/major histocompatibility
      complexes.

PMID- 1349536
TI  - Assessing and ensuring drug compliance in chronic respiratory disease. SEPCR-ERS
      Workshop. Wiesbaden, 1990.

PMID- 1349537
TI  - Quercetin, a bioflavonoid, inhibits the increase of human multidrug resistance
      gene (MDR1) expression caused by arsenite.
AB  - Expression of the MDR1 gene, which encodes P-glycoprotein, is increased under
      some stress conditions. We have reported that quercetin, a bioflavonoid, inhibits
      the expression of heat-shock proteins. We have identified the effects of
      quercetin on the MDR1 gene expression in the human hepatocarcinoma cells line,
      HepG2. The increase of P-glycoprotein synthesis and MDR1 mRNA accumulation caused
      by exposure to arsenite were inhibited by quercetin. The CAT assay suggested that
      quercetin suppressed the transcriptional activation of the MDR1 gene after
      exposure to arsenite. Although many drugs that prevent the P-glycoprotein
      function have been reported, this is the first report to describe the inhibition
      of MDR1 expression by a reagent.

PMID- 1349538
TI  - Codependence: a nursing issue.

PMID- 1349535
TI  - Is there a dopaminergic projection from the A11 catecholamine cell group to the
      amygdala?
AB  - The dopaminergic nature of the pathway from the subparafascicular thalamic
      nucleus and its adjacent region to the amygdala was reexamined by means of
      retrograde fluorescent tracers coupled with tyrosine hydroxylase (TH)
      immunofluorescence. After injecting a small amount of tracer into the amygdala,
      retrogradely labeled cells were found in the subparafascicular thalamic nucleus
      and its adjacent periventricular region. TH immunofluorescence showed that these
      labeled cells completely lacked TH immunoreactivity. Similar results were
      obtained when a larger amount of tracer was applied to the amygdala. The present
      study, in contrast to the previous report describing the dopaminergic innervation
      of the amygdala by the cells in and around the subparafascicular area (A11
      catecholamine cell group), indicates that the A11 cell group does not contribute
      to a dopaminergic input to the amygdala.

PMID- 1349539
TI  - Analysis of mouse Evx genes: Evx-1 displays graded expression in the primitive
      streak.
AB  - Two mouse genes, Evx-1 and Evx-2, each encoding a homeodomain closely related to
      that of the Drosophila even-skipped gene were isolated using a PCR-based
      strategy. The structure and sequence of these genes are described. Mapping
      studies localized Evx-1 to chromosome 6, near the Hox-1 gene cluster, and Evx-2
      to chromosome 2, near the Hox-4 cluster. The evolutionary implications of these
      linkages are discussed. RNA in situ hybridization analysis of Evx expression in
      embryos demonstrated a striking pattern of Evx-1 expression during gastrulation,
      whereas Evx-2 RNA could not be detected at any stage by this technique. Evx-1 RNA
      is first detected shortly before the onset of gastrulation in a region of
      ectoderm containing cells that will soon be found in the primitive streak. This
      localized expression of Evx-1 provides the first molecular evidence for regional
      differences in the mouse embryonic ectoderm before gastrulation. Throughout
      gastrulation, Evx-1 expression is limited to cells near and within the streak and
      that expression is graded, with a posterior-to-anterior decrease in the level of
      RNA. Based on fate-mapping studies indicating that different types of mesoderm
      emerge from different regions of the primitive streak and our observation that
      high levels of expression are localized to the region that will give rise to
      extraembryonic and ventral mesoderm, we speculate that Evx-1 plays a role in the
      dorsoventral specification of mesodermal cell fate.

PMID- 1349540
TI  - Physician extenders: who is using them?
AB  - BACKGROUND: Nurse practitioners and physician assistants (physician extenders)
      are playing an increased role in medical care. The purpose of this research was
      to determine the proportion of adults who have received health care from
      physician extenders. METHODS: This study used the subject population of the 1990
      Kentucky Health Survey, a probability survey of all households in Kentucky. Study
      personnel contacted subjects using random digit telephone dialing. Subjects were
      then interviewed to ascertain whether subjects had received health care from
      physician extenders and whether they were satisfied with that care. RESULTS: Of
      687 participating subjects, 25% had received care from physician extenders during
      the previous two years, primarily for minor problems and routine checkups. More
      than 90% of these subjects reported satisfaction with the care they received.
      Users of physician extenders did not differ from nonusers with respect to income,
      education, insurance status, self-assessment of health status, or rural versus
      urban location. Men used physician extenders more frequently than women.
      CONCLUSIONS: A substantial proportion of the population has used physician
      extenders. Patient satisfaction with physician extenders is high. Use of
      physician extenders may be an effective strategy for improving delivery of
      primary care.

PMID- 1349542
TI  - Immunohistochemical staining of gallbladders from patients with
      pancreaticobiliary maljunction by antibody to proliferating cell nuclear antigen.

PMID- 1349541
TI  - Effect of luminal administration of thyrotropin-releasing hormone or somatostatin
      on gastric pH and interaction of these peptides in rats.
AB  - The effect of intraluminal administration of thyrotropin-releasing hormone (TRH)
      on gastric pH and release of luminal somatostatin, and a possible
      interrelationship between TRH and somatostatin in the rat stomach were studied.
      TRH was administered into the stomach via an intragastric tube at various doses
      (50 pg/kg-10 micrograms/kg) and gastric pH was measured after 15 min. The
      intraluminal administration of TRH significantly decreased gastric pH at doses
      over 1.0 ng/kg. Time-course studies at a dose of 100 ng/kg TRH exhibited a
      significant decrease in gastric pH at 15, 30 and 60 min. Furthermore, TRH
      administration caused a significant increase in immunoreactive-somatostatin (ir
      somatostatin) concentrations in the gastric wall and a significant decrease in ir
      somatostatin concentrations in the gastric juice. On the other hand, intraluminal
      administration of somatostatin caused a significant increase in ir-TRH
      concentrations in the gastric wall and a significant decrease in ir-TRH
      concentrations in the gastric juice, and significantly raised gastric pH at 5
      min. These findings suggest that luminal TRH may exert a regulatory effect on
      gastric acid secretion, and that TRH may have a possible interaction with
      somatostatin in the modulation of gastric acid secretion.

PMID- 1349543
TI  - Production of hemagglutinins and pili by Vibrio mimicus and its adherence to
      human and rabbit small intestines in vitro.
AB  - Clinical isolate of Vibrio mimicus were examined for production of cell
      associated hemagglutinin (HA) and pili and for adherence to formalin-fixed human
      intestinal mucosa. V. mimicus grown on CFA agar for 3 h at 37 degrees C possessed
      HA and adhered better to the mucus layer than to the epithelial cell surface. A
      significant correlation was found between the HA titers and adherence ability to
      the epithelial cell surface of villi (P less than 0.05); adherence to the ileal
      lymphoid follicle-associated epithelium occurred at higher levels. In contrast,
      V. mimicus grown on CFA agar for 20 h at 37 degrees C exhibited lower levels of
      HA and reduced adherence ability. The production of pili was more pronounced
      after 20 h of incubation than after 3 h of incubation. In comparison with V.
      cholerae 01 and V. cholerae non-01 cultured under similar conditions, V. mimicus
      showed inferior adherence, but with similar HA production or piliation.

PMID- 1349544
TI  - Clonal differences within M-types of the group A Streptococcus revealed by pulsed
      field gel electrophoresis.
AB  - Digestion of chromosomal DNA with the rare cutting restriction enzyme SfiI in
      association with pulsed field gel electrophoresis was used to observe restriction
      fragment length polymorphisms (RFLP) among isolates of group A Streptococcus.
      Streptococci examined included isolates belonging to the same M-type
      (epidemiologically related and unrelated), and isolates from other M-types. RFLP
      patterns were quite distinct between all serotypes tested. More importantly,
      isolates from within a serotype could be differentiated by this technique.

PMID- 1349545
TI  - apterous, a gene required for imaginal disc development in Drosophila encodes a
      member of the LIM family of developmental regulatory proteins.
AB  - The apterous (ap) gene is required for the normal development of the wing and
      haltere imaginal discs in Drosophila melanogaster. ap encodes a new member of the
      LIM family of developmental regulatory genes. The deduced amino acid sequence of
      ap predicts a homeo domain and a cysteine/histidine-rich domain known as the LIM
      domain. In these domains ap is highly similar to the mec-3 and lin-11 proteins of
      Caenorhabditis elegans and to the vertebrate insulin enhancer-binding protein isl
      1. ap is presumably required for transcriptional regulation of genes involved in
      wing and haltere development. The nature of the defects in homozygous null mutant
      flies is consistent with the pattern of ap expression in the larval imaginal
      discs. ap is also expressed in a complex pattern in the embryo, including
      portions of the peripheral nervous system (PNS) and central nervous system (CNS).
      A requirement for ap expression in the larval and adult CNS may be the underlying
      cause of the defects in hormone production and vitellogenesis described for ap
      mutations.

PMID- 1349546
TI  - [Psychopharmacology and clinical aspects of benzodiazepine dependence].
AB  - Recent aspects of mechanism of benzodiazepines (BDZ) via indirect GABA-mimetic
      inhibitory effects at brain-specific BDZ-GABA receptors may contribute to an
      understanding of pathophysiological mechanisms of anxiety disorders and drug
      dependencies. The development of various BDZ receptor ligands with diverse
      psychopharmacological properties may lead to safer drugs with regard to "drug
      seeking" and "maintaining" properties. This paper reviews recent research of BDZ
      receptor pharmacology and clinical aspects of abstinence syndromes including also
      prospective studies.

PMID- 1349549
TI  - Advances in Gastroenterology in the Nineties. Symposium proceedings. Seville,
      June 21-22, 1991.

PMID- 1349547
TI  - [Drug-induced headache].
AB  - Migraine or tension-type headache lasting for several years is frequently
      complicated by chronic daily headaches. Those patients recurrently take
      analgesics or ergotamines. Headache induced by chronic ergotamine use is well
      known. Recent studies, however, have shown that a similar form of headache is
      caused by analgesic abuse. Treatment of drug-induced headaches envisages
      withdrawal of the headache medication.

PMID- 1349548
TI  - Lessons from animal experiments in myocarditis.
AB  - We have developed murine models of viral myocarditis induced by
      encephalomyocarditis (EMC) virus in which severe myocarditis, congestive heart
      failure and dilated cardiomyopathy occur in high incidence. From these models, we
      have learned the natural history and pathogenesis and assessed new diagnostic
      methods and therapeutic and preventive interventions. Mural thrombi in the atria
      and ventricles, ventricular aneurysms, conduction disturbance and various
      arrhythmias were seen in these models. Anti-heart antibody were found in sera of
      mice and myosin isoenzyme were changed during the course of EMC virus
      myocarditis. Atrial natriuretic polypeptide was markedly increased in the
      ventricles in these mice. Successive infection with coxsackievirus and EMC virus
      developed lesions similar to chronic myocarditis. The myocardial uptake of
      antimyosin antibody was proved to be a useful method of diagnosis of myocarditis.
      Treatment with the nucleoside analogue, ribavirin and recombinant alpha
      interferon effectively inhibited myocardial virus replication and reduced
      myocardial damage. Passive immunization and virus-specific vaccine prevented
      development of myocarditis. The use of immunosuppressive therapy was associated
      with greater mortality when administered early in illness and beneficial effects
      were not seen by later administration. Angiotensin-converting enzyme inhibitor
      improved myocardial injury and congestive heart failure. A nonselective beta
      adrenergic blocker with intrinsic sympathomimetic activity, carteolol, prevented
      the development of myocardial lesions similar to those in dilated cardiomyopathy
      after myocarditis in the chronic stage.

PMID- 1349550
TI  - Medical treatment of gastroesophageal reflux disease: options and priorities.
AB  - Gastroesophageal reflux disease (GERD) represents a spectra of symptoms and of
      reflux damage to the esophagus. This reflux damage is due to a prolonged acid
      exposure of the esophagus arising from an imbalance between protective motility
      factors and aggressive acid secretory factors. Initially, patients may be managed
      by modifying their food intake and by supportive anti-gravity measures. However,
      many individuals will require drug therapy. Symptomatic relief can be achieved
      with pro-kinetic agents, antacids, sucralfate suspension, H2-receptor antagonists
      and H(+)-K+ ATPase pump blockers. There are limitations in the study design of
      experiments which have compared one agent with another. Accepting these design
      limitations, it would appear that pump blockers lead to higher rates of
      endoscopic healing than the use of standard doses of H2-receptor antagonists.
      However, higher doses of H2-receptor antagonists will likely give higher rates of
      symptomatic relief and endoscopic healing of GERD. Recurrence of symptoms and
      esophagitis occur in a high proportion of patients with GERD, and some patients
      may need to be considered for maintenance therapy.

PMID- 1349551
TI  - Treatment of peptic ulcer disease: is Helicobacter pylori a consideration?

PMID- 1349552
TI  - Potent versus mild acid suppression in peptic ulcer disease.
AB  - In the consideration of potent versus mild suppression of gastric acid secretion
      in the treatment of peptic ulcer disease, it must be remembered that
      pharmacological effect in terms of degree of suppression of acidity is closely
      linked to therapeutic efficacy in terms of numbers of ulcers healed. More potent
      degrees of suppression of acidity result in faster ulcer healing. Moderate
      suppression of acidity, such as is achieved by the H2RA, can heal just as many
      ulcers if treatment is continued longer. Mild acid suppression will take still
      longer to produce the same healing rates. Therapeutic benefit of any treatment
      must be assessed also in terms of the side-effect profile of the drug or drugs
      used. There is an enormous cumulative experience with the H2RA as a group and
      they are known to have an excellent safety profile.

PMID- 1349553
TI  - Short- and long-term management of peptic ulcer disease: current role of H2
      antagonists.
AB  - With numerous active agents available to treat peptic ulcer disease both acutely
      and long-term, this paper reviews various aspects of these agents and their
      effect on the disease process, reviewing efficacy, compliance, incidence of
      relapse, side-effect profile, drug interactions and the effect on the natural
      history of peptic ulcer disease. Helicobacter pylori is obviously a factor in the
      occurrence of peptic ulcer disease, but with the high prevalence of asymptomatic
      infection and evidence suggesting that duodenal ulcer disease may be self
      limiting, widespread treatment with bismuth and antibiotics may do more harm than
      good. Maintenance therapy is recommended for the patient with previous bleeding
      or other complication, the patient with severe symptoms, and the patient with
      frequent recurrences. Maintenance therapy appears to reduce the complication rate
      in the patient with previous bleeding and possibly in the patient with
      uncomplicated disease, although the incidence of complications in this group is
      quite low.

PMID- 1349554
TI  - First-pass metabolism of ethanol: its role as a determinant of blood alcohol
      levels after drinking.

PMID- 1349556
TI  - Parathyroid hyperplasia in multiple endocrine neoplasia type 1: a pathological
      and immunohistochemical reappraisal.
AB  - Twenty-nine parathyroid glands from nine patients with multiple endocrine
      neoplasia type 1 (MEN 1) syndrome were examined histopathologically and
      immunocytochemically to characterize better the nature of the accompanying
      parathyroid hyperplasia. The parathyroids showed varying degrees of nodular and
      diffuse (partial and total) hyperplastic involvement as well as apparently normal
      tissue. The nodules were usually multiple within any one gland and showed a
      varied cytoarchitectural pattern. All glands studied showed both cellular
      argyrophilia and parathyroid hormone immunoreactivity. The staining pattern for
      parathyroid hormone ranged from negative or weak to strong and from patchy to
      diffuse in hyperplastic tissue from different glands and within the same gland.
      Apparently normal areas usually showed the strongest positive reaction. Amyloid
      material was observed within glandular lumens from hyperplastic areas in over
      half of the studied cases and stained positively for parathyroid hormone. This
      suggests that the hormone could be the precursor molecule of parathyroid amyloid
      as occurs with hormone-derived amyloid from other endocrine tumours. The overall
      findings indicate that the most striking feature of the parathyroid glands in MEN
      1 is their variability, both morphological and functional, as indicated by their
      parathyroid hormone immunoreactivity.

PMID- 1349555
TI  - Induction by cortisol of aminopeptidases production from the human placenta in
      tissue culture.
AB  - Human placental aminopeptidase M and A and post-proline endopeptidase are known
      to act as degrading enzymes of bioactive peptides such as angiotensin II,
      oxytocin and endogenous opioids. We tested the effects of cortisol on the
      activities of human placental aminopeptidase A and M and post-proline
      endopeptidase using short-cultured placental tissues. From 34.5 nM to 3.45 microM
      of cortisol significantly increased the activities of 3 enzymes. Our present data
      suggest a possible important role of cortisol in the growth of human placenta via
      induction of placental aminopeptidases.

PMID- 1349557
TI  - An empirical review of the impact of triplicate prescription of benzodiazepines.
AB  - In 1989 New York became the first state to add benzodiazepines to the list of
      controlled substances requiring a triplicate prescription, allowing the state to
      track prescribing patterns and target providers, pharmacies, and patients for
      investigation when misuse is suspected. Studies by the state reporting that
      regulation has significantly reduced inappropriate prescribing and illicit
      diversion of benzodiazepines without affecting legitimate prescribing practices
      are being challenged by other studies showing that patients with legitimate needs
      for benzodiazepines are being denied them, often after abrupt discontinuation.
      Several reports indicate a significant increase in the prescribing of
      benzodiazepine substitutes that are less safe and effective, along with increased
      overdoses of some substitute drugs. Changes in physicians' legitimate prescribing
      practices may reflect their fears of the damage to career and peace of mind that
      follows investigations by regulatory agencies.

PMID- 1349558
TI  - APA report summarizes recent developments in prevention and treatment of tardive
      dyskinesia.

PMID- 1349559
TI  - Prenatal diagnosis of 21-hydroxylase deficiency congenital adrenal hyperplasia
      using the polymerase chain reaction.
AB  - We present an improved method for the prenatal diagnosis of congenital adrenal
      hyperplasia due to steroid 21-hydroxylase deficiency. The polymerase chain
      reaction (PCR) was used to analyze DNA from an affected index case, the parents,
      and a cultured chorionic villus sample, for point mutations in the steroid 21
      hydroxylase (CYP21) gene. We can predict that the fetus is an unaffected carrier.

PMID- 1349560
TI  - Glucose-6-phosphate dehydrogenase (G6PD) electrophoretic variants and the PvuII
      polymorphism in southern African populations.
AB  - Southern African Bantu-speaking negroid and San populations were examined with
      regard to the glucose-6-phosphate dehydrogenase (G6PD) PvuII restriction fragment
      length polymorphism (RFLP) showing alleles of 4 kb and 1.6 kb, called Type 1 and
      Type 2, respectively. The standardized disequilibrium coefficient for the
      electrophoretic G6PD types and PvuII alleles in the Southern African population
      was 0.28. The molecular lesion causing the GdA mutation is the same in the San
      and Southern African negroid populations. GdA chromosomes are found in
      association with both the Type 1 and Type 2 alleles, whereas none of the 62 GdB
      chromosomes from the Southern African populations had the Type 2 allele. Five of
      the 44 GdB chromosomes studied in the American Black population had the Type 2
      allele, indicating that the GdB allele in the two populations may have different
      origins. The presence of all 3 A- deficiency mutations in the G6PD A gene, in a
      region where the ancestral population was thought to have predominantly G6PD B,
      may be explained by their origin in Africa after the divergence of the races.

PMID- 1349561
TI  - Genotype mosaicism in fragile X fetal tissues.
AB  - The fragile X syndrome is one of the most common familial causes of mental
      retardation. It is associated with the expression of a fragile site at Xq27.3,
      although not all individuals carrying the mutation are fragile-X-positive.
      Recently, the mutation causing this disease has been identified as the
      amplification of, or insertion into, a CGG repeat sequence at the fragile site.
      The mutated chromosome can be recognised by the decrease in mobility of the EcoRI
      fragment that covers the mutated region. Analysis of lymphocytes of affected
      males often gives a number of different sized fragments indicating somatic
      heterogeneity. We have investigated this mosaicism in various tissues of an
      affected fetus in order to determine the extent of the variation between tissues,
      and to ascertain how to interpret the results in lymphocytes. Our results suggest
      that the heterogeneity occurs in all fetal tissues, but that the pattern of
      fragments observed varies between tissues. Methylation across the region also
      varies. These differences may be reflected in the cellular phenotypes and may
      influence the ultimate expression of the clinical phenotype.

PMID- 1349562
TI  - Highly polymorphic region of the human prothrombin (F2) gene.
AB  - We have found a highly polymorphic region in the human prothrombin gene. Our
      sequence differed from that previously reported at as many as 6 positions in a
      225-bp stretch spanning exon 6 and its flanking regions; four of these positions
      were related to endonuclease restriction sites for AluI, HpaII(MspI), MboII, and
      NcoI. AluI and HpaII digested all alleles of the Japanese tested. MboII and NcoI
      restriction fragment length polymorphisms are highly heterozygous and not in
      linkage disequilibrium; they thus serve as good human DNA markers.

PMID- 1349563
TI  - Anonymous markers located on chromosome 6 in the HLA-A class I region: allelic
      distribution in genetic haemochromatosis.
AB  - Two yeast artificial chromosomes of the HLA class I region were subcloned. Four
      of the subclones studied displayed restriction polymorphisms that corresponded to
      six bi-allelic series. Allelic distribution of the anonymous markers was then
      studied by comparing a control population with a group of patients with familial
      haemochromatosis. Only one marker presents an unequivocal association with the
      haemochromatosis gene and is 100 kb centromeric to HLA-A. This association
      however is not as strong as with HLA-A3. The results suggest two possible
      locations for the haemochromatosis gene: less than 100 kb centromeric to the HLA
      A locus, or on the telomeric side.

PMID- 1349564
TI  - Alpha alpha alpha alpha anti-3.7 type II: a new alpha-globin gene rearrangement
      suggesting that the alpha-globin gene duplication could be caused by
      intrachromosomal recombination.
AB  - We report here a new human alpha-globin gene rearrangement carrying the two
      normal, alpha 2 and alpha 1, and two hybrid, alpha 1/alpha 2, globin genes in the
      order 5'-alpha 2-alpha 1/alpha 2-alpha 1/alpha 2-alpha 1-3'. Both the hybrid
      genes, subtyped with ApaI and RsaI restriction enzymes, were found to be of the
      uncommon anti 3.7 type II. The hybrid genes were expressed at the biosynthetic
      level and their interaction with the beta-thalassaemia IVS 1 nt 1 G----A mutation
      caused thalassaemia intermedia. We also report a case of an alpha alpha alpha
      globin gene rearrangement in the twin of one of the alpha alpha alpha alpha
      globin gene carriers; the duplicated gene was of the anti 4.2 type and was
      associated with the absence of RsaI polymorphism. The singular finding of an
      alpha alpha alpha alpha-anti 3.7 cluster with two identical rare hybrid genes
      suggests that the reciprocal unequal recombination causing the alpha-globin gene
      rearrangements could be of the intrachromosomal rather than the interchromosomal
      type.

PMID- 1349565
TI  - Allotype distribution of human T cell receptor beta and gamma chain genes in
      Caucasians, Asians and Australian aborigines: relevance to chronic hepatitis B.
AB  - RFLPs of TCR beta and gamma genes have been analyzed in chronic HBV carriers of
      three different ethnic populations to determine if there is an association of TCR
      allotypes with the development of chronic hepatitis B. The RFLPs of TCR beta and
      gamma genes were defined respectively by BglII and PvuII genomic fragments on
      Southern blots. These methods allow allotype assignment. The distribution of TCR
      beta alleles showed ethnic variation, with one allele significantly decreased in
      Australian Aborigines, but there was no association with chronic hepatitis B. The
      distribution of TCR gamma alleles did not show ethnic variation. However, a
      significant frequency decrease of one allele occurred in Aboriginal HBV carriers,
      suggesting the possibility of involvement of TCR gamma allotypes in the
      development of the chronic HBV carrier state in Australian Aborigines.

PMID- 1349566
TI  - Linkage disequilibrium between phenylketonuria and RFLP haplotype 1 at the
      phenylalanine hydroxylase locus in Portugal.
AB  - RFLPs of 36 normal and 41 mutant alleles at the phenylalanine hydroxylase locus
      were determined in 31 Portuguese kindreds. A total of 14 haplotypes including 10
      normal and 7 mutant alleles were observed. Almost 75% of all mutant alleles were
      confined within only two haplotypes, namely haplotype 9 (17.1%) and haplotype 1
      (56.1%). This frequency of mutant haplotype 1 in Portugal is, to our knowledge,
      the highest for this mutant haplotype in all studies reported to date. Other
      mutant haplotypes were either rare (haplotype 2, 9.7%) or totally absent
      (haplotype 3, 0%). Only 24.5% of all mutant alleles were found to consistently
      carry identified mutations, particularly R261Q (9.8%), R252W (3.3%), R408W (1.6%)
      and delta I94 (3.3%). A new mutation, L249F, located in the seventh exon of the
      gene, accounted for 6.5% of all mutant alleles in our series. Interestingly, this
      mutant genotype was consistently associated with mutant haplotype 1 (P less than
      0.01), as also observed for the R261Q mutation. It appears, therefore, that
      mutant haplotype 1 is genotypically heterogeneous in Portugal and that more than
      two mutations account for its prevalence in this country.

PMID- 1349567
TI  - Screening for nonsense mutations in patients with severe hemophilia A can provide
      rapid, direct carrier detection.
AB  - Despite marked genetic heterogeneity in families with hemophilic patients,
      transition mutations in CG dinucleotides occur frequently. Of 71 CG dinucleotides
      in the factor VIII cDNA, a C-to-T transition in 12 would lead to a new Stop codon
      (CGA to TGA). Using restriction enzyme digestion of 11 amplified DNA fragments,
      seven point mutations were localized among 60 patients with severe hemophilia A.
      Five were detected as loss of a natural or introduced TaqI site at codons -5,
      583, 1941, 2116, and 2209 and were confirmed as CGA (Arg) to TGA (Stop) nonsense
      mutations by DNA sequencing. A novel C-to-T nonsense mutation was detected as
      loss of the RsaI site at codon 1966 and confirmed by sequence in two unrelated
      individuals. Two partial gene deletions were detected as selective failure to
      amplify exon 1 and exons 15-22, respectively. In an additional (61st) patient who
      was subsequently found to have mild (instead of severe) hemophilia, digests
      suggested a mutation in codon 1696. Upon sequencing, this codon contained a novel
      missense mutation, a C-to-G transversion changing CGA (Arg 1696) to GGA (Gly). In
      four families with women available for testing, carrier status was rapidly
      determined by direct screening for the point mutation. In two of three with
      sporadic occurrences, the mother was a carrier as were two of four sisters. In
      the other family, the mother and a sister were homozygous for the TaqI cleavage
      site in their amplified exon 24 fragment, indicating a de novo C-to-T transition
      in codon 2209 in the patient's factor VIII gene. This final patient's sister was
      a noncarrier even though by linkage analysis she inherited the same factor VIII
      gene as her brother.

PMID- 1349568
TI  - Polymerase chain reaction-based genotyping for allotypic markers of
      immunoglobulin kappa shows allelic association of Km with kappa variable segment.
AB  - Allotypic markers of immunoglobulin kappa (Km) may be determined using a novel
      method of amplification of the constant segment (C kappa) (IGKC) by polymerase
      chain reaction (PCR) followed by restriction enzyme digestion. Restriction sites
      in the C kappa PCR product correlate with allotypic differences among Km(1),
      Km(1,2), and Km(3) alleles. An AccI site in the PCR product correlates with
      Km(3); and presence or absence of a MaeII site correlates with the Km(1) or
      Km(1,2) allele, respectively. Km allelic frequencies were determined in a
      Caucasian population and compared to genotypic frequencies of nearby polymorphic
      markers. Among unrelated individuals with rheumatoid arthritis (RA) and controls,
      there is no evidence of allelic association between CD8A and polymorphic markers
      of the immunoglobulin kappa region [a V kappa (IGKV) BglII polymorphism about 24
      kb centromeric to C kappa, Km allotype, and a SacI polymorphism 3.5 kb telomeric
      to the C kappa segment]. Similarly, there is no allelic association of the SacI C
      kappa polymorphism with Km or with the BglII V kappa polymorphism. However, there
      is evidence of allelic association of V kappa B3 and Km, specifically between the
      V kappa BglII 2.2-kb allele and Km(3) and also between the V kappa 3.5-kb allele
      and Km(1,2). Therefore, Km typing by PCR-based methods suggests the presence of
      allelic association between polymorphisms within the coding region of the C kappa
      segment and the nearest V kappa segment.

PMID- 1349569
TI  - A high-resolution cytogenetic map of 168 cosmid DNA markers for human chromosome
      11.
AB  - We have constructed a high-resolution cytogenetic map with 168 DNA markers,
      including 90 RFLP markers for human chromosome 11. The cosmid clones were mapped
      by fluorescence in situ suppression hybridization, in which discrete fluorescent
      signals can be detected directly on prometaphase R-banded chromosomes. Although
      these cosmid clones were distributed throughout the chromosome, they had some
      tendency to localize in the regions of R-positive band, such as 11p15, 11p11.2,
      11q13, 11q23, and 11q25. Since these regions of chromosome 11 are considered to
      contain genes responsible for certain genetic diseases, cancer breakpoints
      involved in chromosome rearrangements, and tumor-suppressor genes, this high
      resolution cytogenetic map will contribute to the molecular characterization of
      such genes. This map will also provide many landmarks essential for construction
      of the complete physical map with contigs of cosmid and YAC clones.

PMID- 1349570
TI  - Fine genetic localization of the gene for autosomal dominant polycystic kidney
      disease (PKD1) with respect to physically mapped markers.
AB  - PKD1, the gene for the chromosome 16-linked form of autosomal dominant polycystic
      kidney disease, has previously been genetically mapped to an interval bounded by
      the polymorphic loci Fr3-42/EKMDA2 distally and O327hb/O90a proximally. More
      recently, 26.6PROX was identified as the closest proximal flanking locus. We set
      out to refine the localization of PKD1 by identifying a series of single
      recombinant events between the flanking markers Fr3-42/EKMDA2 and O327hb/O90a and
      analyzing them with a new set of polymorphic loci that have been physically
      mapped within the PKD1 interval. We identified 11 such crossovers in eight
      families; 6 of these fell into the interval between GGG1 and 26.6PROX, a distance
      of less than 750 kb. Three of these crossovers placed PKD1 proximal to GGG1 and
      two crossovers placed PKD1 distal to 26.6PROX. Both of the latter also placed
      PKD1 telomeric to a locus 92.6SH1.0, which lies 200-250 kb distal to 26.6PROX.
      The sixth recombinant, however, placed the disease mutation proximal to the locus
      92.6SH1.0. Several possible explanations for these observations are discussed. An
      intensive study to locate deletions, insertions, and other chromosomal
      rearrangements associated with PKD1 mutations failed to detect any such
      abnormalities. Thus we have defined, in genetic and physical terms, the segment
      of 16p13.3 where PKD1 resides and conclude that a gene-by-gene analysis of the
      region will be necessary to identify the mutation(s).

PMID- 1349571
TI  - A 14-Mb physical map of the region at chromosome 11q13 harboring the MEN1 locus
      and the tumor amplicon region.
AB  - We have constructed a physical map of chromosome 11q13, using 54 DNA markers that
      had been localized to 11q13.1----q13.5 by means of somatic hybrid cell panels.
      Although the map has some gaps, it spans nearly 14 Mb and includes the region
      containing the gene responsible for multiple endocrine neoplasia type 1 (MEN1)
      and also the region that is amplified in several types of malignant tumors. As
      the estimated average distance between each locus is roughly 300 kb, the markers
      reported here will be valuable resources for construction of contig maps with
      yeast artificial chromosomes and/or cosmid clones. Furthermore, these clones will
      be useful in efforts to identify the MEN1 gene and in analyses of the
      amplification units present at 11q13 in certain tumors.

PMID- 1349573
TI  - Close linkage of the olfactory marker protein gene to the mouse deafness mutation
      shaker-1.
AB  - One thousand sixty-six progeny have been generated from a backcross segregating
      for the mouse deafness mutation, shaker-1 (sh-1). One thousand fifty-two mice
      were analyzed for a protein polymorphism segregating for the distal flanking
      marker, beta-globin (Hbb), and 13 recombinants between Hbb and sh-1 were
      identified. One thousand eight mice were analyzed for a restriction fragment
      length polymorphism segregating for the proximal flanking marker, tyrosinase (c),
      and 54 recombinants between c and sh-1 were identified, completing a panel of 67
      recombinant mice from the backcross in the vicinity of the sh-1 mutation. This
      panel allows the identification of markers closely linked to the sh-1 mutation
      that may act as start points for a chromosomal walk to the gene. One such marker,
      the olfactory marker protein gene (Omp), is recombinant with sh-1 in only one
      mouse from the recombinant panel. Thus, the Omp gene lies 0.1 cM from sh-1, on
      average, a distance of 200 kb. Haplotype analysis indicates that Omp lies
      proximal to sh-1.

PMID- 1349572
TI  - Physical mapping of 14 new DNA markers isolated from the human distal Xp region.
AB  - We have isolated 14 new DNA markers from the human Xpter-Xp21 region distal to
      the Duchenne muscular dystrophy gene by targeted cloning, employing two somatic
      cell hybrids containing this region as their sole human material. High-resolution
      physical localization of these markers within this region was obtained by
      hybridization to two mapping panels consisting of DNA from patients carrying
      various translocations and deletions in distal Xp. Five markers were assigned to
      the pseudoautosomal region where their position on the long-range map of this
      region was further determined by pulsed-field gel electrophoresis. The other nine
      markers map to the X-specific region. Informative TaqI restriction fragment
      length polymorphisms were observed for four loci. One of these represents a
      region-specific low-copy repeated element. These 14 new markers represent useful
      tools for the understanding of distal Xp deletion and translocation mechanisms
      and for the positional cloning of disease genes in the region.

PMID- 1349574
TI  - The D4 dopamine receptor (DRD4) maps to distal 11p close to HRAS.
AB  - Dopaminergic pathophysiology is important in several psychiatric illnesses. The
      recently cloned D4 dopamine receptor gene (DRD4) shows considerable homology to
      the D2 and D3 dopamine receptors (DRD2 and DRD3); pharmacologically, its affinity
      for the atypical antipsychotic clozapine is much higher than that of these other
      dopamine receptors. Probe pB28 for this locus recognizes an informative HincII
      polymorphism. We typed this polymorphism on several large reference families (a
      total of about 271 individuals) to place DRD4 in the genetic linkage map.
      Pairwise linkage analysis (using ILINK) provided evidence for close linkage to
      the distal 11p loci tyrosine hydroxylase (TH) and the Harvey ras oncogene (HRAS).
      We used our version of LINKMAP adapted to run under distributed parallel
      processing (Linda-LINKMAP) for an analysis moving DRD4 across a fixed map with
      HRAS set 3.8 cM distal to TH. This localized DRD4 close to HRAS, with no
      crossovers observed between those loci and a maximum lod score of 19.9 (2 cM
      distal to HRAS). The one LOD unit support interval extends from about 1 cM
      proximal to HRAS to 8 cM distal to HRAS. Crossovers identified in one kindred
      place DRD4 distal to TH, providing further evidence for its location close to
      HRAS, making DRD4 one of the most telomeric of 11p markers. (This also places
      DRD4 in band 11p15.5.)

PMID- 1349575
TI  - A glycine-to-glutamate substitution abolishes alanine:glyoxylate aminotransferase
      catalytic activity in a subset of patients with primary hyperoxaluria type 1.
AB  - We have synthesized and sequenced alanine:glyoxylate aminotransferase (AGT; HGMW
      approved symbol for the gene--AGXT) cDNA from the liver of a primary
      hyperoxaluria type 1 (PH1) patient who had normal levels of hepatic peroxisomal
      immunoreactive AGT protein, but no AGT catalytic activity. This revealed the
      presence of a single point mutation (G----A at cDNA nucleotide 367), which is
      predicted to cause a glycine-to-glutamate substitution at residue 82 of the AGT
      protein. This mutation is located in exon 2 of the AGT gene and leads to the loss
      of an AvaI restriction site. Exon 2-specific PCR followed by AvaI digestion
      showed that this patient was homozygous for this mutation. In addition, three
      other PH1 patients, one related to and two unrelated to, but with enzymological
      phenotype similar to that of the first patient, were also shown to be homozygous
      for the mutation. However, one other phenotypically similar PH1 patient was shown
      to lack this mutation. The mechanism by which the glycine-to-glutamate
      substitution at residue 82 causes loss of catalytic activity remains to be
      resolved. However, the protein sequence in this region is highly conserved
      between different mammals, and the substitution at residue 82 is predicted to
      cause significant local structural alterations.

PMID- 1349576
TI  - Identification of three novel PKU mutations among Chinese: evidence for
      recombination or recurrent mutation at the PAH locus.
AB  - Three novel mutations have been identified in the phenylalanine hydroxylase (PAH)
      genes of Chinese classical phenylketonuria (PKU) patients. Two of these
      substitutions (W326X and Y356X) result in the generation of a premature stop
      codon, while the third (IVS-7nt2) alters an invariant dinucleotide splicing
      signal. These mutations together account for about 10% of all PKU alleles in the
      Chinese population. The W326X mutation is associated with PAH RFLP haplotype 4,
      the most common haplotype in Orientals, while the IVS-7nt2 mutation occurs once
      on a haplotype 7 chromosome. The Y356X mutation is associated with multiple
      haplotypes, possibly due to crossover, gene conversion, or recurrent mutation.

PMID- 1349577
TI  - Additional RFLPs at D10S94 and the development of PCR-based variant detection
      systems: implications for disease genotype prediction in MEN 2A, MEN 2B, and MTC1
      families.

PMID- 1349578
TI  - Nucleotide sequence of mouse Sry gene is different between Y chromosome
      originating from Mus musculus musculus and Mus musculus domesticus.

PMID- 1349579
TI  - Characterization of radiation/fusion hybrids containing parts of human chromosome
      10 and their use in mapping chromosome 10-specific probes.
AB  - We have characterized a panel of somatic cell hybrid cell lines which contain
      different portions of human chromosome 10. Genomic DNA from the somatic cell
      hybrids was tested for hybridization with each of an ordered set of probes used
      previously to construct a genetic map of chromosome 10, as well as several
      additional probes, previously localized by in situ hybridization. Hybridization
      of an unmapped probe to the cell line DNAs can be used to determine its most
      likely position on the chromosome relative to the mapped set of probes. Genomic
      DNA from two of the cell lines has been used to construct region-specific cosmid
      and bacteriophage libraries, and clones derived from these libraries were
      localized by hybridization to the panel of hybrid cell lines. Several of these
      probes reveal restriction fragment length polymorphisms which have been
      genetically mapped. Three of the probes map near the locus for multiple endocrine
      neoplasia type 2A, and one of these probes, BG-JC353 (D10S167), maps between RBP3
      and TB14.34 (D10S34). Another probe, CRI-J282 (D10S104), is close to the FNRB
      locus. The panel of hybrid cell lines is thus useful for rapidly localizing
      unmapped probes and as a source of DNA for the construction of recombinant
      libraries derived from specific regions of the chromosome.

PMID- 1349580
TI  - Human-mouse homologies in the region of the polycystic kidney disease gene
      (PKD1).
AB  - Autosomal dominant polycystic kidney disease (PKD1) is linked to the alpha-globin
      locus near the telomere of chromosome 16p. We established the existence of a
      conserved linkage group in mouse by mapping conserved sequences and cDNAs from
      the region surrounding the PKD1 gene in the mouse genome. Results obtained with
      the BXD recombinant strain system and somatic cell hybrids show the homologous
      region to be located on mouse chromosome 17 near the globin pseudogene Hba-ps4,
      an unprocessed alpha-like globin gene. The markers we mapped are widely
      distributed over the region known to contain the PKD1 gene, and it is therefore
      likely that the mouse homologue of PKD1 is also located on mouse chromosome 17.

PMID- 1349581
TI  - Wobbler, a mutation affecting motoneuron survival and gonadal functions in the
      mouse, maps to proximal chromosome 11.
AB  - The wobbler mouse (genotype wr/wr) has been considered as an animal model for
      human neurodegenerative disorders. In the homozygous condition, the autosomal
      mutation wobbler (wr) causes a motoneuron disease and gonadal dysfunction. We
      have genetically mapped the wr gene, using an interspecific backcross between the
      laboratory strain C57BL/6J (wr/+) and Mus spretus. The expected percentage of
      wobbler progeny were obtained, but heterogeneous expression of the wobbler
      phenotype indicated the existence of modifier genes in the M. spretus genetic
      background. The segregation of DNA markers of known chromosomal location among
      wobbler progeny and unaffected mice was scored. Close linkage of wr was obtained
      with Erbb and Rel on chromosome 11 and the gene order cen-Nfh-Erbb-wr-Rel-Hba-Il
      3 was established. Closely linked markers like Erbb provide tools for a
      prognostic DNA diagnosis of the wobbler disease, and thereby for its analysis by
      descriptive and experimental embryology.

PMID- 1349582
TI  - A minisatellite and a microsatellite polymorphism within 1.5 kb at the human
      muscle glycogen phosphorylase (PYGM) locus can be amplified by PCR and have
      combined informativeness of PIC 0.95.
AB  - We sequenced a genomic clone (pMCMP1), previously reported to detect a VNTR
      polymorphism at the PYGM locus, and found a dinucleotide repeat segment
      (CA)14(GA)25 and a complex (AT)-repeat-rich segment containing 63 repeats
      spanning 160 bp. Resolution of PCR-amplified genomic DNA from the (CA)(GA) repeat
      region on DNA sequencing gels revealed a highly informative polymorphism with
      alleles differing by 2-bp intervals and ranging in size from 156 to 190 bp. Among
      three racial groups, a total of 18 alleles were observed. Fourteen alleles were
      observed in Caucasians (PIC 0.89), 12 alleles in American Blacks (PIC 0.89), and
      9 alleles in Pima Indians (PIC 0.73). PCR amplification of the (AT) repeat region
      and resolution of the products on DNA sequencing gels revealed a complex variable
      length polymorphism with alleles distributed in size from 367 to 970 bp. Twenty
      eight alleles were found in American Blacks (PIC 0.94), 6 alleles in Pima Indians
      (PIC 0.70), and 11 alleles in Caucasians (PIC 0.71). Comparison of the previously
      described VNTR RFLP alleles visualized by Southern hybridization to the PCR
      products described in this report demonstrated that the polymorphism described in
      both assays was identical. However, a larger number of alleles could be detected
      from the PCR-amplified products. Combined informativeness, PIC 0.95, for the two
      polymorphisms was determined from haplotype analysis of 100 Caucasian
      chromosomes. Therefore, for genotyping purposes, informativeness is maximized
      from using both polymorphisms.

PMID- 1349583
TI  - Amplification of human polymorphic sites in the X-chromosomal region q21.33 to
      q24: DXS17, DXS87, DXS287, and alpha-galactosidase A.
AB  - Methods for the PCR amplification of five polymorphic sites in the region Xq21.33
      to Xq24 were developed and used to predict heterozygosity for Fabry disease in
      informative families. Clones containing polymorphic sites associated with DNA
      segments DXS17, DXS87, and DXS287, and the alpha-galactosidase A gene were
      isolated from genomic libraries. Surrounding nucleotide sequences and optimal
      conditions for amplification of each polymorphic site were determined. These
      amplifiable polymorphisms provided predictions of heterozygosity for Fabry
      disease and should be useful for diagnostic linkage analyses in Alport syndrome,
      X-linked cleft palate and ankyloglossia, Pelizaeus-Merzbacher disease, and X
      linked agammaglobulinemia as well as sequence-tagged sites for gene mapping.

PMID- 1349584
TI  - An approach to the localization of the susceptibility genes for generalized
      myasthenia gravis by mapping recombinant ancestral haplotypes.
AB  - The association of HLA A1, B8, and DR3 with generalized myasthenia gravis (GMG)
      in Caucasoids is well established, but no particular gene has been implicated and
      there is still no adequate explanation in functional terms. In this study we have
      taken advantage of sequential genomic markers between B8 and DR3 so as to map the
      location of susceptibility gene(s) on the A1, B8, DR3 (8.1) ancestral haplotype.
      By studying 51 patients, we have delineated a region between HLA B and TNF which
      is shared by 29/29 patients with B8 and DR3, 19/19 patients with B8 but not DR3
      and 2/3 patients with DR3 but not B8. The potential importance of this region was
      confirmed by examining a similar disease induced by D-Penicillamine (D-PenMG) and
      associated with different HLA class II alleles (DR1 and/or DR7). Among these
      patients, 7/16 (44%) have B8, often with other markers of 8.1. These results
      implicate at least two categories of genes in determining susceptibility to MG;
      one located in the region between HLA B and TNF may be immunoregulatory, whereas
      the second, located in the class II region, may relate to the inducing factor
      (e.g., DR1 or DR7 in D-PenMG).

PMID- 1349586
TI  - Immunogenetics of multiple sclerosis and optic neuritis: DNA polymorphism of HLA
      class II genes.

PMID- 1349587
TI  - Genetic mapping of the gene coding for the integrin beta 7 subunit to the distal
      part of mouse chromosome 15.

PMID- 1349585
TI  - Genomic DNA sequence and organization of a TL-like gene in the grc-G/C region of
      the rat.
AB  - Genes in the grc-G/C region, which is linked to the rat major histocompatibility
      complex, influence the control of growth, development, and susceptibility to
      chemical carcinogens. As an initial approach to analyzing the structure and
      organization of these genes, a class I hybridizing fragment designated RT(5.8)
      was isolated from an R21 genomic DNA library and sequenced from overlapping
      restriction enzyme fragments. The RT(5.8) clone has 5788 base pairs and contains
      the eight exons characteristic of a class I gene. There are CAAT and TATA boxes
      upstream of the signal peptide, and the recognition sequence that precedes the
      site of polyadenylation is located downstream from the third cytoplasmic domain.
      Comparison of the RT(5.8) gene with representative class I genes from the rat and
      other species shows that the nucleotide sequences of RT(5.8) have a high level of
      similarity to those of TL region genes of several strains of mice. The peptide
      sequence deduced from the RT(5.8) clone is distinct from all previously published
      class I gene sequences, and at many positions there are amino acid residues that
      are unique to the RT(5.8) sequence. Probes have been isolated from the third exon
      and from the 5' and 3' flanking regions of the RT(5.8) clone, and Southern blot
      analysis with genomic DNA of various rat strains shows that these probes are
      specific for the RT(5.8) fragment. Northern blot analysis shows that the gene is
      transcribed in the thymus but not in the liver or spleen. The RT(5.8) sequence is
      more similar to some mouse TL genes (especially in the alpha 2 and cytoplasmic
      domains and in the 5' and 3' untranslated regions) than it is to other rat class
      I genes. Hence, TL-like genes are not restricted to the mouse.

PMID- 1349588
TI  - Synthesis and release of neuroactive substances by glial cells.
AB  - Glia contain, synthesize, or release more than 20 neuroactive compounds including
      neuropeptides, amino acid transmitters, eicosanoids, steroids, and growth
      factors. The stimuli that elicit release differ among compounds but include
      neuropeptides, neurotransmitters, receptor agonists, and elevated external [K+].
      The mechanisms of release are poorly understood in most cases. Many of the
      neuroactive compounds are localized in discrete subpopulations of glia. Thus,
      glia are equipped to send as well as receive chemical messages and appear to be
      present as classes of cells with differing abilities to communicate chemically.
      It is possible that glia are as diverse as neurons in their functional
      characteristics.

PMID- 1349589
TI  - Spontaneous changes in intracellular calcium concentration in type I astrocytes
      from rat cerebral cortex in primary culture.
AB  - Measurement of fura-2 fluorescence in type I astrocytes from rat cerebral cortex
      showed that the intracellular calcium ion concentration undergoes very large
      spontaneous changes. These spike-like changes ranged from resting levels of
      calcium of 50-250 nM to as high as 1-2 microM. The spikes were found to be
      irregular in frequency and amplitude and were frequently synchronous in confluent
      cultures. The synchronous events appeared as propagating waves that spread over
      many cells. The spontaneous spikes persisted when the extracellular calcium
      concentration was reduced to below micromolar levels suggesting that the source
      for the increases in [Ca2+]i was intracellular. Treatment of the astrocytes with
      tetrodotoxin did not abolish the spontaneous changes, nor did blockade of voltage
      dependent calcium channels with nimodipine and D-600. Ryanodine, a blocker of the
      sarcoplasmic reticulum calcium-induced calcium release channel, was also without
      effect. These changes in [Ca2+]i were different in character from both agonist
      induced oscillations and depolarization-induced increases in intracellular
      calcium concentration. Depolarization using 25-100 mM [K+]o resulted in a prompt
      rise in intracellular calcium concentration, which returned to near resting
      levels, and this response was sensitive to removal of extracellular calcium and
      voltage-gated calcium channel antagonists. L-glutamate (0.5-100 microM) caused
      large increases in [Ca2+]i that were associated with discrete periodic
      oscillations in some cells. The cellular trigger for the spontaneous spikes is
      currently not understood. We conclude that spontaneous changes in [Ca2+]i in
      astrocytes are distinct from agonist-induced and membrane potential
      depolarization-induced changes.

PMID- 1349590
TI  - Influence of serum progesterone levels at the time of hCG on the release of ova
      during hMG cycles.
AB  - A study was designed to monitor release of ova by sonography in hMG-treated
      patients following hCG and to determine if failure to release ova correlates with
      critically low or high progesterone levels. This was a retrospective study of 292
      consecutive patients treated with hMG. The requirement for treatment was that hCG
      be given when at least one follicle attained a 17-mm diameter with a serum
      estradiol level of at least 200 pg/mL per mature follicle. If the serum
      progesterone assay was greater than or equal to 1.8 ng/mL, then hCG would be
      given as long as there was at least one dominant follicle and a serum estradiol
      level greater than 200 pg/mL. The patients were divided into four groups for
      study based on the progesterone level at the time of hCG administration. There
      were no statistically significant differences in the ability to achieve ova
      release whether serum progesterone was very low or close to 2 ng/mL when hCG was
      given. The rise in the progesterone level prior to ovulation has been proposed to
      enhance egg release. However, the data presented herein do not support the
      necessity for a critical level of serum progesterone at the time of hCG injection
      in hMG-treated women.

PMID- 1349591
TI  - Transcervical fallopian tube recanalization: a safe and effective therapy for
      patients with proximal tubal obstruction.
AB  - Over a 13-month period, 14 patients with proximal tubal obstruction underwent
      transcervical fallopian tube recanalization under fluoroscopic guidance in an
      outpatient setting at the hospital of the University of Pennsylvania. Twenty-one
      of 24 attempted tubal dilations (87.5%) were successful, as demonstrated by tubal
      opacification and contrast spillage into the peritoneal cavity at the conclusion
      of the procedure. Four intrauterine pregnancies, and no ectopic pregnancies, have
      followed the recanalization. One pregnancy ended in an early miscarriage, one
      patient delivered a healthy term female, and two pregnancies are ongoing at
      greater than twenty weeks' gestation. Two procedure-related complications
      occurred: in one patient, the isthmic segment of a fallopian tube was perforated,
      but healed without incident, and another patient experienced a low-grade fever,
      which resolved with p.o. antibiotics. We therefore conclude that fallopian tube
      recanalization is a well-tolerated, safe, and effective procedure for the
      treatment of proximal tubal occlusion.

PMID- 1349592
TI  - Further evidence concerning catecholamine metabolism in polycystic ovary syndrome
      following Gn-RH administration.
AB  - The role of catecholamine activity in the GnRH-LH system among cases of
      polycystic ovary syndrome was investigated by high-performance liquid
      chromatography using an electrochemical detector. We measured plasma levels of
      catecholamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4
      dihydroxyphenylacetic acid (DOPAC), in relation to LH-RH administration in 23
      women with polycystic ovary syndrome. MHPG concentrations were significantly
      higher in polycystic ovary syndrome patients than in ten control subjects in
      early follicular phase. The peak values of LH after LH-RH administration were
      significantly correlated with plasma MHPG concentrations. These data suggest that
      an excess of norepinephrine is present in polycystic ovary syndrome and that the
      hypophyseal response to LH-RH administration is correlated with catecholamine,
      especially norepinephrine activity.

PMID- 1349593
TI  - Comparison of the adrenocorticotropic hormone stimulation test in the follicular
      and luteal phases of the menstrual cycle.
AB  - A comparison was made of the ACTH stimulation test in the proliferative and
      luteal phases of the menstrual cycle in 13 subjects, each of whom served as her
      own control. The test yielded a 53.9% false-positive rate in the luteal phase.
      The study, therefore, clearly shows that from a practical, clinical point of
      view, the test is completely unreliable in the luteal phase, and is only valid
      when carried out in the follicular phase of the cycle.

PMID- 1349594
TI  - Annual and sub-annual rhythms in human conception rates. I. Effective correction
      and use of public record LMP dates.
AB  - Most studies of rhythms in human conception rates have used monthly total births
      back-dated 9 months. Such data are of little use for studying any pattern less
      than a few months in length. Even at that level, they are poor material for
      studying the possibility of altered conception rhythms in anomalous births. The
      high frequency of premature delivery in such births makes a simple 9-month offset
      simplistic and misleading. Dates of last normal menses (LMP) provide appropriate
      detail, but have generally been dismissed as unreliable. In a large public birth
      record dataset, we have identified a clear artifact of poor LMP recall, highly
      correlated with passage of time between conception and onset of prenatal care.
      The majority of the variation in daily LMP counts due to this recall artifact can
      be corrected statistically to yield population data suitable to more detailed
      analyses.

PMID- 1349595
TI  - Argon laser laparoscopy: an effective technique for conservative treatment of
      unruptured ectopic pregnancy.
AB  - Between October 1987 and January 1990, 60 patients with unruptured ectopic
      pregnancy in the ampullary portion of the tube were treated with linear
      salpingotomy, using the argon laser laparoscopically. In all cases, salpingotomy
      was performed by the "bare-fiber" technique, with a power of 3-6 watts. The same
      fiber was used for incision and coagulation either with a contact or a non
      contact technique. There were no instrument-related intra- or postoperative
      complications. Twenty-four patients were evaluated by second-look laparoscopy or
      hysterosalpingography for tube patency and possible formation of adhesions. In
      all of these patients the tubes were patent. In one patient, the tube failed to
      close, resulting in a fistula. Four patients had filmy adhesions, covering the
      tube near the incision site. There were no adhesions covering the distal part of
      the tube.

PMID- 1349596
TI  - Follicular phase hormonal profiles during administration of leuprolide for in
      vitro fertilization.
AB  - Hormonal changes induced during short-term administration of leuprolide were
      evaluated during the follicular phase in 57 patients who completed an IVF cycle.
      They were compared with those of 14 patients who were placed on long-term
      suppression. There was an unexpected abnormal increase in serum progesterone
      during the first week of the cycle in nine of the 57, with no significant change
      in the fertilization and cleavage rate; however, no pregnancy was achieved in
      this group. Transient mild elevation of progesterone was also detected in 16
      patients with no adverse effect on fertilization and the outcome of the IVF. In
      the long protocol, the tonic levels of LH, FSH, and progesterone remained low
      throughout the follicular phase. The total number of pregnancies was higher in
      the short suppression regimen, but the full-term pregnancy rates were similar in
      both protocols.

PMID- 1349597
TI  - The effect of insulin on in vitro progesterone production of human granulosa
      cells.
AB  - Insulin appears to play an important role in regulating ovarian function in some
      mammals. The present study assessed the effect of insulin on progesterone
      production by human granulosa lutein (G-L) cells in vitro. G-L cells were
      isolated from individual follicles at the time of laparoscopy for oocyte
      retrieval in patients undergoing in vitro fertilization/embryo transfer (IVF/ET).
      G-L cells were purified and plated for culture. Control wells contained no
      additions, while insulin was added to test wells. Although G-L cells obtained
      from follicles which contain an oocyte that subsequently fertilizes in vitro
      produce more progesterone at three and six days of culture than G-L cells from
      follicles that contain an oocyte that does not fertilize in vitro, insulin is
      unable to increase further the progesterone production of G-L cells from
      follicles containing either fertilized or nonfertilized oocytes at days 3 and 6
      in culture. Further analysis based on the stimulation protocol (follicle
      stimulating hormone, n = 13; clomiphene citrate/hMG, n = 19; hMG, n = 10) also
      failed to yield a significant difference in basal or insulin-stimulated
      progesterone secretion after three or six days in culture. The lack of an effect
      of insulin on progesterone production by G-L cells in vitro may indicate that
      these cells are maximally stimulated following hyperstimulation and cannot
      increase progesterone production further, or may signify that insulin has no
      effect on the in vitro luteinization of human G-L cells obtained from
      hyperstimulated cycles.

PMID- 1349598
TI  - Ultrastructural features of round-headed human spermatozoa.
AB  - Two cases of the round-headed spermatozoa syndrome are described, with the main
      emphasis on the ultrastructural features of the spermatozoa. Essentially, the
      first type (type I) of these cells has round heads, lacks an acrosome and its
      intrinsic enzymes, and lacks a postacrosomal sheath; patients with this condition
      are absolutely infertile. This is the classical Schirren-Holstein model for the
      round-headed spermatozoon. Other types of round-headed spermatozoa might exist
      (Type II), which may possess remnants of the acrosome and are capable of
      fertilisation.

PMID- 1349599
TI  - [Safety in the treatment of bladder incontinence. II. Specialty press workshop on
      the occasion of the 22nd Congress of the International Society of Urology.
      Seville, 4 November 1991].

PMID- 1349600
TI  - Measurement of cell proliferation in gastric carcinoma: comparative analysis of
      Ki-67 and proliferative cell nuclear antigen (PCNA).
AB  - Immunostaining to identify nuclear antigens expressed throughout the cell cycle
      provides a convenient way of assessing proliferating kinetics in tumours. We
      studied proliferation activity of gastric carcinomas by Ki-67 and PCNA
      immunostaining and the two methods were compared. The mode of tissue preparation
      differed, fresh frozen for Ki-67 and formalin-fixed paraffin-embedded for PCNA.
      Immunostaining with avidin-biotin was used in both. The labelling index (LI) and
      a semi-quantitative grading of cell proliferation were assessed in both markers.
      Significant correlation was shown between LI and grading with either Ki-67 and
      PCNA. However, no correlation was found between PCNA and Ki-67. This lack of
      relationship between the two markers may be attributed to a number of factors. 1.
      The most likely is the marked inter- and intra-tumour heterogeneity of gastric
      carcinomas reflected in high standard deviation values. 2. Preparation of tissue
      and small size sampling with Ki-67. 3. Long life of PCNA leading to detection of
      cells that have recently left the cell cycle. 4. One may be observing deregulated
      expression of DNA as seen in certain tumours. PCNA offers the advantage of being
      applicable to archival material.

PMID- 1349601
TI  - Coexpression of UmuD' with UmuC suppresses the UV mutagenesis deficiency of groE
      mutants.
AB  - The GroE proteins of Escherichia coli are heat shock proteins which have also
      been shown to be molecular chaperone proteins. Our previous work has shown that
      the GroE proteins of E. coli are required for UV mutagenesis. This process
      requires the umuDC genes which are regulated by the SOS regulon. As part of the
      UV mutagenesis pathway, the product of the umuD gene, UmuD, is
      posttranslationally cleaved to yield the active form, UmuD'. In order to
      investigate what role the groE gene products play in UV mutagenesis, we measured
      UV mutagenesis in groE+ and groE strains which were expressing either the umuDC
      or umuD'C genes. We found that expression of umuD' instead of umuD will suppress
      the nonmutability conferred by the groE mutations. However, cleavage of UmuD to
      UmuD' is unaffected by mutations at the groE locus. Instead we found that the
      presence of UmuD' increased the stability of UmuC in groE strains. In addition,
      we obtained evidence which indicates that GroEL interacts directly with UmuC.

PMID- 1349602
TI  - Cloning, sequencing, and molecular analysis of the groESL operon of Clostridium
      acetobutylicum.
AB  - The groESL operon of Clostridium acetobutylicum was cloned in Escherichia coli by
      using a gene probe of E. coli groESL. Sequencing of a positively reacting 2.2-kbp
      HindIII fragment contained in the recombinant plasmid pFN1 and a 2.5-kbp XbaI
      fragment present in pFN4 revealed that both fragments partially overlapped and
      together spanned 3,493 bp of the clostridial chromosome. Two complete open
      reading frames (288 and 1632 bp) were found and identified as the groES- and
      groEL-homologous genes of C. acetobutylicum, respectively. The 3' end of a third
      gene (orfZ), which was divergently transcribed, showed no significant homology to
      other sequences available in the EMBL and GenBank data bases. The length of the
      groESL-specific mRNA (2.2 kb), a transcription terminator downstream of groEL,
      and a transcription start site upstream of groES, identified by primer extension
      analysis, indicated that groES and groEL of C. acetobutylicum are organized in a
      bicistronic operon. From the transcription start site, the promoter structure 5'
      TTGCTA (17 bp) TATTAT that shows high homology to the consensus promoter sequence
      of gram-positive bacteria as well as E. coli was deduced. Transcription of the
      groESL operon was strongly heat inducible, and maximum levels of mRNA were
      detected 15 min after heat shock from 30 to 42 degrees C. An 11-bp inverted
      repeat, located between promoter and translation start sites of groES and
      partially identical with similar structures in front of several heat shock genes
      of other bacteria, may play an important role in the regulation of heat shock
      gene expression in this organism.

PMID- 1349603
TI  - Electrostatic interactions stabilizing ferredoxin electron transfer complexes.
      Disruption by "conservative" mutations.
AB  - Mitochondrial ferredoxins mediate electron transfer from NADPH:ferredoxin
      oxidoreductase to cytochrome P450 enzymes. Previous studies on human ferredoxin,
      in which acidic residues were replaced with neutral amino acids, established that
      Asp-76 and Asp-79 are are important for binding to both reductase and P450
      (Coghlan, V. M., and Vickery, L. E. (1991) J. Biol. Chem. 266, 18606-18612). Here
      we report that replacement of Asp----Glu at position 76 or 79, whereas
      maintaining negative charge at these positions also results in dramatic decreases
      in binding affinity for both electron transfer partners (5-100-fold, delta(delta
      G) approximately 1.0-2.8 kcal/mol). These results imply that the active electron
      transfer complexes in these systems are dominated by a stable form which requires
      specific pairwise electrostatic interactions of fixed geometry for recognition
      and binding. This mechanism contrasts with that proposed for other electron
      transfer systems (as exemplified by cytochrome c) in which electrostatic
      interactions are believed to function primarily in precollisional orientation
      leading to "encounter complexes" having multiple geometries of similar free
      energy.

PMID- 1349604
TI  - Removal of the amino-terminal acidic residues of yeast actin. Studies in vitro
      and in vivo.
AB  - We have examined the role of the acidic residues Asp2 and Glu4 at the NH2
      terminus of Saccharomyces cerevisiae actin through site-directed mutagenesis. In
      DNEQ actin, these residues have been changed to Asn2 and Gln4, whereas in delta
      DSE actin, the Asp2-Ser-Glu tripeptide has been deleted. Both mutant actins can
      replace wild type yeast actin. Peptide mapping studies reveal that DNEQ, like
      wild type actin, retains the initiator Met and is NH2 terminally acetylated,
      whereas delta DSE has a free NH2 terminus and has lost the initiator Met.
      Interestingly, microscopic examination of filaments of these two actins reveal
      the appearance of bundled filaments. The DNEQ bundles are smaller and more
      ordered, whereas the delta DSE bundles are larger and more loosely organized.
      Additionally, both mutant actins activate the ATPase activity of rabbit muscle
      myosin S1 fragment to a lesser extent than wild type. We have also developed a
      sensitive assay for actin function in vivo that enabled us to detect a slight
      defect in the ability of these mutant actins to support secretion, an important
      function in yeast. Thus, although the mutant actins resulted in no gross
      phenotypic changes, we were able to detect a defect in actin function through
      this assay. From these studies we can conclude that 1) although NH2-terminal
      negative charges are not essential to yeast life, the loss of such charges does
      result in a slight defect in the actins' ability to support secretion, 2) removal
      of the NH2-terminal negative charges promotes the bundling of actin filaments,
      and 3) actins lacking NH2-terminal negative charges are unable to activate the
      myosin S1 ATPase activity as well as wild type actin.

PMID- 1349605
TI  - Mass spectrometry of mRNA cap 4 from trypanosomatids reveals two novel
      nucleosides.
AB  - Synthesis of mRNA in kinetoplastid protozoa involves the process of trans
      splicing, in which an identical 39-41-nucleotide (depending on the species) mini
      exon is placed at the 5' end of mature mRNAs. The mini-exon sequence is highly
      conserved among all members of the Kinetoplastida, nucleotides 1-6 being
      identical in the four genera so far examined. Prior to trans-splicing, the mini
      exon donor RNA is capped by the addition of a (5'-5') triphosphate-linked 7
      methylguanosine, followed by modification of the first four transcribed
      nucleotides. Partial structures have been previously deduced for this cap 4
      moiety from Trypanosoma brucei and Leptomonas collosoma. We have purified enough
      cap 4 from T. brucei and Crithidia fasciculata to allow definitive structural
      analysis by combined liquid chromatography/mass spectrometry and gas
      chromatography/mass spectrometry. The results, together with the known mini-exon
      sequence, show that cap 4 in both species has the structure
      m7G(5')ppp(5')m6(2)AmpAmpCmpm3Ump. The presence of N6,N6,2'-O-trimethyladenosine
      and 3,2'-O-dimethyluridine, nucleosides previously unknown in nature, were
      confirmed by rigorous comparison with synthetic standards. The conservation of
      cap 4 between these divergent genera suggests that this structure may be common
      to most if not all Kinetoplastida.

PMID- 1349606
TI  - Factors determining the specificity of signal transduction by guanine nucleotide
      binding protein-coupled receptors. I. Coupling of alpha 2-adrenergic receptor
      subtypes to distinct G-proteins.
AB  - alpha 2-Adrenergic receptor (alpha 2-AR) subtypes couple to pertussis toxin (PT)
      sensitive G-proteins to elicit both stimulatory and inhibitory cell responses.
      Signal specificity may be generated by the ability of the receptor subtypes to
      "recognize" distinct G-proteins with different affinity. To address this issue we
      stably expressed three alpha 2-AR subtypes, RNG alpha 2 (alpha 2B-AR), RG10
      (alpha 2C-AR), and RG20 (alpha 2D-AR), in NIH-3T3 fibroblasts, which express two
      PT-sensitive G-proteins (Gi alpha 2, Gi alpha 3), and analyzed receptor/G-protein
      interactions by determining: 1) functional coupling to adenylylcyclase and 2) the
      ability of the receptors to exist in a high affinity state for agonist. In alpha
      2D-AR transfectants expressing 200 or 2,200 fmol of receptor/mg of protein,
      epinephrine (10 microM) inhibited forskolin-induced elevation of cellular cAMP by
      26 +/- 4.8% and 72 +/- 6.2%, respectively. Similar results were obtained in alpha
      2B-AR transfectants. However, in alpha 2C-AR transfectants (200 fmol/mg) the
      forskolin-induced elevation of cellular cAMP was not altered by agonist
      treatment. In alpha 2C-AR transfectants expressing higher receptor densities (650
      1,200 fmol/mg), epinephrine inhibited the effect of forskolin by 30 +/- 3.2%.
      This difference in functional coupling among the alpha 2-AR subtypes is reflected
      at the receptor/G-protein interface. In membrane preparations of alpha 2B and
      alpha 2D-AR but not alpha 2C-AR transfectants, agonist competition curves were
      biphasic, indicating high and low affinity states of the receptor for agonist.
      The high affinity state was guanyl-5'-yl imidodiphosphate- and PT-sensitive,
      indicative of receptor/G-protein coupling. These data suggest that the alpha 2C
      AR differs from the alpha 2B and alpha 2D-AR subtypes in its ability to recognize
      PT-sensitive G-proteins expressed in NIH-3T3 fibroblasts. The alpha 2C-AR may
      couple preferentially to PT-sensitive G-proteins (Gi1, Go1,2) not expressed in
      NIH-3T3 fibroblasts and thereby elicit different cellular responses.

PMID- 1349607
TI  - Factors determining the specificity of signal transduction by guanine nucleotide
      binding protein-coupled receptors. II. Preferential coupling of the alpha 2C
      adrenergic receptor to the guanine nucleotide-binding protein, Go.
AB  - Cell to cell communication by many hormones and neurotransmitters involves three
      major entities: receptor (R), G-protein (G), and effector molecule (E).
      Plasticity in this system is conferred by the existence of each entity as
      isoforms or closely related subtypes that are expressed in a tissue-specific and
      developmentally regulated manner. Factors that determine signal specificity in
      this system are poorly understood. Such factors include the relative affinity and
      stoichiometry of R-G or G-E and the possible colocalization of R-G-E in cellular
      microdomains. Utilizing the alpha 2-adrenergic receptor (alpha 2-AR) system as a
      representative subfamily of this class of signal transducers, we determined the
      relative importance of these factors. By analysis of R-G coupling in mammalian
      cells cotransfected with alpha 2-AR genes and G alpha cDNA, we demonstrate
      preferential coupling between an alpha 2-AR subtype and Go. Our data implicate R
      G affinity as an important determinant of signal transduction specificity and
      indicate that a critical level of Go alpha is required for coupling. This report
      indicates the utility of R-G cotransfection in mammalian cells as a "natural
      environment model" to characterize events occurring at the R-G and G-E interface.

PMID- 1349608
TI  - Accumulation of a microtubule-binding protein, pp170, at desmosomal plaques.
AB  - The establishment of epithelial cell polarity correlates with the formation of
      specialized cell-cell junctions and striking changes in the organization of
      microtubules. A significant fraction of the microtubules in MDCK cells become
      stabilized, noncentrosomally organized, and arranged in longitudinal bundles in
      the apical-basal axis. This correlation suggests a functional link between cell
      cell junction formation and control of microtubule organization. We have followed
      the distribution of pp170, a recently described microtubule-binding protein,
      during establishment of epithelial cell polarity. This protein shows the typical
      patchy distribution along microtubules in subconfluent fibroblasts and epithelial
      cells, often associated with the peripheral ends of a subpopulation of
      microtubules. In contrast to its localization in confluent fibroblasts (A72) and
      HeLa cells, however, pp170 accumulates in patches delineating the regions of cell
      cell contacts in confluent polarizing epithelial cells (MDCK and Caco-2). Double
      immunolocalization with antibodies specific for cell-cell junction proteins,
      confocal microscopy, and immunoelectron microscopy on polarized MDCK cells
      suggest that pp170 accumulates at desmosomal plaques. Furthermore, microtubules
      and desmosomes are found in close contact. Maintenance of the desmosomal
      association of pp170 is dependent on intact microtubules in 3-d-old, but not in 1
      d-old MDCK cell cultures. This suggests a regulated interaction between
      microtubules and desmosomes and a role for pp170 in the control of changes in the
      properties of microtubules induced by epithelial cell-cell junction formation.

PMID- 1349610
TI  - Hypertension in the elderly.
AB  - More than 50% of the U.S. population 65 years and older have elevated systolic
      pressure with or without elevated diastolic pressure--and thus in either case are
      at risk for cerebrovascular and cardiovascular sequelae. As therapy lowers
      diastolic pressure, however, mortality can increase, presumably when blood
      pressure is brought down to levels that compromise perfusion.

PMID- 1349611
TI  - [The site of action of growth hormone in the brain].

PMID- 1349612
TI  - Isolation and purification of human endometrial stromal and glandular cells using
      immunomagnetic microspheres.
AB  - Isolation of pure preparations of the different cell populations of human
      endometrium is a prerequisite for studies of in-vitro function. Sieving of
      dispersed endometrial cells, followed by adsorption onto immunomagnetic
      microspheres coated with antibody to Thy-1 was used to separate glandular and
      stromal cells. The purity of these cell populations was checked with antibodies
      to cytokeratin and Thy-1. The stromal cells were 98% pure and 90% viable, gland
      cells were 82% pure with 76% viability. The purified cells were able to
      proliferate in vitro as shown by thymidine incorporation.

PMID- 1349609
TI  - Expression of SV-40 T antigen in the small intestinal epithelium of transgenic
      mice results in proliferative changes in the crypt and reentry of villus
      associated enterocytes into the cell cycle but has no apparent effect on cellular
      differentiation programs and does not cause neoplastic transformation.
AB  - The mouse intestinal epithelium represents a unique mammalian system for
      examining the relationship between cell division, commitment, and
      differentiation. Proliferation and differentiation are rapid, perpetual, and
      spatially well-organized processes that occur along the crypt-to-villus axis and
      involve clearly defined cell lineages derived from a common multipotent stem cell
      located near the base of each crypt. Nucleotides -1178 to +28 of the rat
      intestinal fatty acid binding protein gene were used to establish three pedigrees
      of transgenic mice that expressed SV-40 large T antigen (TAg) in epithelial cells
      situated in the uppermost portion of small intestinal crypts and in already
      committed, differentiating enterocytes as they exited these crypts and migrated
      up the villus. T antigen production was associated with increases in crypt cell
      proliferation but had no apparent effect on commitment to differentiate along
      enterocytic, enteroendocrine, or Paneth cell lineages. Single- and multilabel
      immunocytochemical studies plus RNA blot hybridization analyses suggested that
      the differentiation programs of these lineages were similar in transgenic mice
      and their normal littermates. This included enterocytes which, based on the
      pattern of [3H]thymidine and 5-bromo-2'-deoxyuridine labeling and proliferating
      nuclear antigen expression, had reentered the cell cycle during their migration
      up the villus. The state of cellular differentiation and/or TAg production
      appeared to affect the nature of the cell cycle; analysis of the ratio of S-phase
      to M-phase cells (collected by metaphase arrest with vincristine) and of the
      intensities of labeling of nuclei by [3H]thymidine indicated that the duration of
      S phase was longer in differentiating, villus-associated enterocytes than in the
      less well-differentiated crypt epithelial cell population and that there may be a
      block at the G2/M boundary. Sustained increases in crypt and villus epithelial
      cell proliferation over a 9-mo period were not associated with the development of
      gut neoplasms--suggesting that tumorigenesis in the intestine may require that
      the initiated cell have many of the properties of the gut stem cell including
      functional anchorage.

PMID- 1349613
TI  - TNF-alpha suppresses CR3-mediated myelin removal by macrophages.
AB  - Mononuclear cells of the monocyte/macrophage system play an important role in
      myelin ingestion during Wallerian degeneration. The present in vitro study
      clarifies the role in this process of two macrophage-secreted cytokines, TNF
      alpha and interleukin-1. Treatment with TNF-alpha massively reduced the amount of
      myelin ingested by macrophages via their complement receptor type 3 (CR3). Anti
      TNF-alpha antibodies reversed the effect. Immunofluorescence of macrophages
      indicated that TNF-alpha caused a reduced expression of the CR3 by phagocytic
      cells. Further experiments revealed an interaction of TNF-alpha with its receptor
      on the macrophage cell membrane. Interleukin-1 had no effect on myelin ingestion
      in the in vitro system used in these experiments.

PMID- 1349614
TI  - Restriction endonuclease analysis of Aspergillus fumigatus DNA.
AB  - AIMS: To develop a genome based DNA fingerprinting system for Aspergillus
      fumigatus mould. METHODS: DNA was extracted from 21 isolates obtained from eight
      patients with an aspergilloma. This was with a freeze-dried mycelial extract
      fragmented in liquid nitrogen. DNA was subsequently purified by phenol-chloroform
      extraction followed by ultracentrifugation on a caesium chloride gradient. The
      DNA was restricted by EcoRI and Xba I. RESULTS: All isolates were identical when
      cut by EcoRI; Xba I delineated six DNA types. CONCLUSIONS: DNA fingerprinting can
      be used to type isolates of A fumigatus. Strains from within an aspergilloma
      which were morphologically distinct could either have the identical DNA
      fingerprint or produce a unique type.

PMID- 1349615
TI  - Pharmacotherapy in the prevention of suicidal behavior.
AB  - Prevention or reduction of suicide remains a serious challenge for the medical
      community. Psychotherapeutic and psychosocial interventions have not been shown
      to reduce the incidence of suicide attempts and analytic psychotherapy has been
      shown to increase suicidal behavior. The efficacy of pharmacotherapy in reducing
      suicide attempts in patients with a history of repeated suicidal behavior has
      been shown with low doses of the neuroleptic agent flupenthixol compared with
      placebo. Supporting findings have been reported with trifluoperazine. There is
      evidence to suggest that some antidepressants may not be neutral in their effect
      on suicidal behavior. Maprotiline, for example, was associated with an increase
      in suicide attempts compared with placebo in a large long-term treatment study
      despite its significant efficacy in preventing relapse of depression.
      Differential lethality indices taken from large community studies support the
      notion that noradrenergic drugs such as maprotiline, desipramine, and
      nortriptyline are associated with a higher than expected incidence of death from
      overdose, and the suicide-provoking potential may relate to some noradrenergic
      property. The studies of serotonergic antidepressants do not suggest that they
      are suicide-provoking agents; rather they appear to be neutral or protective.
      Prospective prophylactic studies are needed to test the ability of potential
      treatments for the reduction of suicidal behavior.

PMID- 1349617
TI  - REAP: an integrated environment for the manipulation and phylogenic analysis of
      restriction data.

PMID- 1349616
TI  - Projections from rabbit caudal medulla to C1 and A5 sympathetic premotor neurons,
      demonstrated with phaseolus leucoagglutinin and herpes simplex virus.
AB  - We combined Phaseolus vulgaris leucoagglutinin anterograde tracing and Herpes
      simplex virus transneuronal retrograde tracing to determine whether neurons in
      the vasodepressor region of the rabbit caudal ventrolateral medulla project to
      brainstem neurons containing the virus after its transneuronal transport from the
      adrenal medulla. Five days after adrenal injection of virus, 764 +/- 159 virus
      positive neurons were found bilaterally in the brainstem: 61% in the C1
      sympathoexcitatory region of the rostral ventrolateral medulla, 30% in the A5
      region, 5% in the parapyramidal region, and 3% in the paraventricular nucleus of
      the hypothalamus. Many of the virus-positive neurons in the C1 and A5 areas also
      contained tyrosine hydroxylase and, in the parapyramidal area, many contained 5
      hydroxytryptamine. After iontophoretic deposit of leucoagglutinin into the
      vasodepressor region of the caudal ventrolateral medulla, brain regions
      containing varicose processes labeled with leucoagglutinin included the regions
      containing virus-positive neurons. We examined the C1 and A5 regions following
      injections of both tracers in the same rabbits, leucoagglutinin into the caudal
      ventrolateral medulla and virus into the adrenal gland. Varicosities containing
      leucoagglutinin were seen in contiguity with perikarya and dendritic branches of
      neurons containing HSV1, in both the C1 and A5 regions. Studies also revealed
      labeled varicosities in contiguity with TH-containing C1 and A5 neurons. The
      projection from the caudal medulla to presumed sympathetic premotor neurons in
      the C1 area, including some C1 cells, represents a potential pathway whereby
      activity of neurons in the caudal medulla could reduce blood pressure by
      inhibiting sympathoexcitatory neurons in the rostral medulla.

PMID- 1349618
TI  - Activation of human phagocytes through carbohydrate antigens (CD15, sialyl-CD15,
      CDw17, and CDw65).
AB  - The leukocyte carbohydrate (CHO) Ag CD15, sialyl-CD15, and CDw65 have recently
      been found to function as ligands for CD62 and ELAM-1 cell adhesion molecules on
      platelets and endothelium, respectively. Cell adhesion ligands also may act as
      receptors capable of signal transduction. We therefore investigated the
      possibility that these CHO Ag and CDw17, a glycolipid Ag whose expression is
      regulated by leukocyte activation, may have receptor-like characteristics. The
      effects of antibody cross-linking of CHO Ag on phagocyte activation were measured
      by using flow cytometry and fluorescent indicators for cytoplasmic calcium ions,
      oxidative burst, and the granule-associated proteins CD11b and CD67. Cross
      linking of CD15, sialyl-CD15, CDw65, or CDw17 induced a moderate release of
      calcium ions into the cytoplasm of granulocytes, a strong activation of oxidative
      burst, and a low up-regulation of CD11b and CD67 compared to the effects of
      treatment with 4 microM FMLP. The results suggest a role for CHO Ag in leukocyte
      signal transduction and support the view that these molecules are involved in
      phagocyte activation.

PMID- 1349619
TI  - Internalization of a major group human rhinovirus does not require cytoplasmic or
      transmembrane domains of ICAM-1.
AB  - Intercellular adhesion molecule-1 (CD54), a cell adhesion molecule and the
      receptor for the major group of rhinoviruses, is a class 1 membrane protein with
      five Ig-like domains in its extracellular region, a transmembrane domain, and a
      short cytoplasmic domain. The amino-terminal domains (D1 and D2) are sufficient
      for virus binding and the first is most important (1). We have investigated
      whether other extracellular domains, transmembrane or cytoplasmic domains are
      required for virus entry as determined by postinfection virion protein
      biosynthesis. We demonstrate that cytoplasmic, transmembrane, and Ig-like domains
      3, 4, and 5 are not essential for rhinovirus entry into transfected COS cells.
      The efficiency of rhinovirus infection directly correlates with the efficiency of
      rhinovirus binding and a form of intercellular adhesion molecule-1 that is
      glycophosphatidyl-inositol anchored, and thus does not extend into the inner
      leaflet of the membrane bilayer or the cytoplasm efficiently supports virus
      entry.

PMID- 1349620
TI  - Causality of relationship between paternal radiation exposure and leukaemia
      incidence in the children of Sellafield workers.

PMID- 1349621
TI  - In vivo protection by the aminothiol WR-2721 against neutron-induced
      carcinogenesis.
AB  - The ability of the compound S-2-(aminopropylamino)ethylphosphorothioic acid,
      designated WR-2721, to protect against neutron-induced carcinogenesis was
      investigated. Both sexes of the B6CF1 mouse were injected i.p. with 400 mg/kg of
      WR-2721 30 min prior to being irradiated by 10 cGy of neutrons. Neoplastic
      mortality in the groups receiving thiol was either reduced or delayed relative to
      irradiated mice not given protector. However, the time at which the protective
      effect of WR-2721 was expressed depended on the sex of the animal. Thiol-related
      shifts in the time of neoplastic death in females occurred only in the first half
      of the lifespan. Once a female survived to the mean age at death, no difference
      in the pattern of mortality could be detected between control and WR-2721-treated
      mice exposed to neutrons. Irrespective of thiol treatment, the timing of tumour
      related death was nearly identical during the first half of life for males
      exposed to neutrons. In the last half of the lifespan, survival of thiol
      protected males was enhanced relative to saline-injected males and even exceeded
      that observed in the control population.

PMID- 1349622
TI  - Reaction of dithiothreitol and para-nitroacetophenone with different radical
      precursors of .OH radical-induced strand break formation of single-stranded DNA
      in anoxic aqueous solution.
AB  - The yields of single-strand breakage (ssb) in single-stranded calf thymus DNA
      (ssDNA) have been determined after 60Co gamma-irradiation of aqueous anoxic
      solutions in the presence of different concentrations of dithiothreitol (DTT),
      ascorbate or trans-4,5-dihydroxy-1,2-dithiane, using low-angle laser light
      scattering. The influence of DTT on the kinetics of ssb formation has been
      determined by conductivity measurements in pulse radiolysis. The results suggest
      that strand breakage in ssDNA proceeds via two modes of about equal contribution
      and with half-lives of about 7 ms and 0.8s, respectively. Both modes reflect
      reactions of at least two DNA radicals, which react with DTT by hydrogen-atom
      transfer reactions with similar rate constants of about 5-9 x 10(5) dm3 mol-1 s
      1. These hydrogen-atom transfer reactions inhibit strand break formation. The
      slow mode is shown to represent the decay of base-radicals to generate sugar
      radicals. The involvement of the oxidizing .OH adduct radical of guanine in the
      formation of strand breaks can be ruled out and there is no evidence for a
      contribution from the anion or radical anion of DTT to the inhibition of strand
      breaks via electron transfer reactions to DNA radicals.

PMID- 1349623
TI  - Catalytic reduction of Fe(III)-cytochrome-c involving stable radiolysis products
      derived from disulphides, proteins and thiols.
AB  - gamma-Radiolysis, with doses less than 1 kGy, of aqueous solutions of
      disulphides, disulphide-proteins or thiols leads to the generation of stable
      products, capable of stimulating the catalytic reduction of Fe(III)-cytochrome-c
      by unirradiated glutathione, and by other thiols. The stimulatory activity fades
      within 20-60 min in the case of irradiated thiols, but there was little loss of
      this activity when irradiated solutions of disulphides or disulphide-proteins
      were stored at 4 degrees C for days. Disulphides (e.g. cystamine) are mainly
      activated by .OH radicals, disulphide-proteins (e.g. alpha-chymotrypsin) mainly
      by e-aq, and thiols (e.g. cysteine) by virtually all water radicals. The
      radiolytic activation, which is only partially prevented by oxygen, can be
      attributed to the generation of trace amounts of higher sulphides and
      persulphides (RSSSR, RSSSSR and RSSH). Such species are known to stimulate
      Fe(III)-cytochrome-c reduction by glutathione in a chain reaction (Massey et al.
      1971). The radiolytic stimulation of reductive catalytic activity of thiols and
      disulphides may play a role in irradiated biological systems, and might be
      exploited to identify irradiated proteins with Fe(III)-cytochrome-c as detector.

PMID- 1349624
TI  - Substituent effects in the free radical reactions of silybin: radiation-induced
      oxidation of the flavonoid at neutral pH.
AB  - Silybin dihemisuccinate sodium salt, a flavonoid used in human therapy of liver
      dysfunction, has an inhibitory effect in vivo on radiation-induced deactivation
      of enzymes and peroxidation of membrane lipids in rat liver microsomes. The
      reactivity of silybin and its phenolic OH groups towards free radicals (OH, N3.,
      (SCN)2.-, Cl3CO2.) in aqueous solution was studied by pulse radiolysis.
      Absorption spectra for the phenoxyl-type radicals were assigned using
      structurally similar models. The one-electron reduction potential for silybin at
      pH 7 (E07 = 0.76 V), determined using the p-methoxy-phenoxyl/phenolate redox
      couple as reference standard (E07 = 0.72 V, Lind et al. 1990), is related to the
      3'-methoxy-4'-OH structure, the exclusive target for one-electron oxidation at pH
      7, while the 7-OH and 5-OH groups are prevented from oxidation by 4-keto
      substitution and intramolecular H-bonding, respectively. The free radical
      reactivity of silybin compares favourably with poly-OH-substituted flavonoids;
      however, the latter compounds have been reported to generate potentially toxic
      oxygen species at a biologically relevant pH.

PMID- 1349625
TI  - Direct comparison between protons and alpha-particles of the same LET: I.
      Irradiation methods and inactivation of asynchronous V79, HeLa and C3H 10T1/2
      cells.
AB  - A direct comparison was carried out of the biological effectiveness of protons
      and alpha-particles of the same linear energy transfer (LET) under identical
      conditions with a variety of in vitro biological systems. Monolayers of mammalian
      cells were irradiated with accelerated beams of protons (1.2 and 1.4 MeV) and
      alpha-particles (30 and 35 MeV) corresponding to LETs of 23 and 20 keV microns-1
      for each particle type. For V79-4 cells it was observed that the linear term of
      the dose-response for cell inactivation by protons was significantly greater than
      that for alpha-particles of the same LET. For HeLa and HeLa S3 cells, also, the
      linear term appeared to be greater for protons, but this was not observed with
      more limited data for C3H 10T1/2 cells. The result for V79 cells is in agreement
      with the report of Belli et al. (1989) who observed that the biological
      effectiveness of protons rose sharply between 17 and 30 keV microns-1 in strong
      contrast to alpha-particles which reached a peak effectiveness at greater than
      100 keV microns-1. These results place new constraints on the biologically
      relevant features of the microscopic structure of radiation tracks, and have
      implications for the mechanistic and practical comparison between radiations.

PMID- 1349626
TI  - Direct comparison of biological effectiveness of protons and alpha-particles of
      the same LET. II. Mutation induction at the HPRT locus in V79 cells.
AB  - Mutation induction at the hprt locus has been studied in V79-4 Chinese hamster
      cells irradiated with mono-energetic protons and alpha-particles with LET of 20.3
      and 23 keV microns-1. The mutation frequency increased linearly with the dose for
      all the four radiation qualities investigated, so that effectiveness for mutation
      induction could be expressed by the slope of the relevant curve. This
      effectiveness did not significantly change with the small change in LET of each
      kind of particle, while sizeable differences were found between particles.
      Protons were more effective in mutation induction than alpha-particles with the
      same LET by a factor of about 2. This finding is similar to, although slightly
      larger than, the factors 1.5-1.8 found for inactivation of the same cells in the
      same series of experiments.

PMID- 1349627
TI  - Direct comparison of biological effectiveness of protons and alpha-particles of
      the same LET. III. Initial yield of DNA double-strand breaks in V79 cells.
AB  - The results reported form part of a series of experiments to substantiate and
      extend the findings by Belli et al. (1989) that protons are more biologically
      effective at cell killing than alpha-particles of the same LET. The irradiations
      were carried out using the Variable Energy Cyclotron (VEC) at the Harwell
      Laboratories. V79-4 Chinese hamster cells were exposed to alpha-particles and
      protons with LETs of 20 and 23 keV microns-1 in the dose range 40-150 Gy. X-rays
      were also used for comparison. Two methods were used for measurement of initial
      DNA double-strand breaks: sedimentation and DNA precipitation assays. The dose
      response relationships were found to be well fitted by straight lines in all
      cases. With the sedimentation assay a slightly lower yield of dsb was found from
      protons than from alpha-particles of the same LET. The yield from X-rays was not
      significantly different from either. The precipitation assay showed similar
      yields of DNA damage from both particle types but significantly higher yields
      from X-rays. This may reflect a difference in the type of lesions scored by the
      two methods. Since the initial amount of dsb does not account for the observed
      differences in cellular response to radiations of different qualities, it is
      likely that these are related to the nature of the dsb (affecting reparability)
      or to the occurrence of other types of molecular damage.

PMID- 1349628
TI  - Kinetics of micronucleus induction by 125I-labelled thyroid hormone in hormone
      responsive cells.
AB  - Two cell lines, CHO and GC, different in their tissue origin, were investigated
      with the aim of discovering the correlation between the level of 125I-T3 binding
      and chromosomal damage induced by 125I decay. Incubation of cells with 125I-T3
      has been performed in two exposure schedules: continuous incubation for one to
      six cell cycles and a pulse-chase schedule involving exposure for one cell cycle.
      The cellular uptake of 125I-T3, its compartmentization and kinetics were
      different in the two cell lines. GC cells contained about 7 times more 125I-T3
      than CHO cells when incubated with the same external 125I activity concentration
      (74 kBq of 125I-T3 ml-1 medium). Approximately 70% of the cellular 125I-T3 was
      found in nuclei of GC cells and only 5% in the nuclei of CHO cells. During the
      long-term incubation of GC cells with 74 kBq of 125I-T3 ml-1 medium, the 125I
      activity concentration in cells and their nuclei initially decreased by a half,
      and thereafter reached a plateau after the third doubling time. In CHO cells and
      nuclei a very slow linear increase of 125I activity was observed. In GC cells,
      micronucleus frequency was found to be correlated with nuclear 125I activity. One
      cell cycle pulse labelling with 74 kBq of 125I-T3 ml-1 medium caused a
      significant enhancement of micronucleus frequency above the control level during
      six doubling times, with a maximum at the first post-labelling doubling time. In
      GC cells continuously incubated with 74 kBq of 125I-T3 ml-1 medium, the
      micronucleus frequency increased with the incubation time. A model of T3 receptor
      dependent dose delivery to nuclei of GC cells continuously incubated with 125I-T3
      is proposed. The frequency of micronuclei in the CHO cell line continuously
      incubated with 125I-T3 did not differ significantly from the control, whereas in
      the pulse-chase schedule the mean frequency of micronucleated binuclear cells was
      lower during 4 post-labelling doubling times (significantly at the first and
      second post-labelling doubling time and insignificantly at the later doubling
      times) than in the control. Incubation of GC cells with various activity
      concentrations in medium for four cell cycles resulted in a linear increase of
      125I activity in cells and nuclei; however, with a saturation in the region of
      highest 125I-T3 concentrations used. The frequency of binuclear cells bearing
      micronuclei was linearly dependent on the nuclear 125I-T3 concentration.

PMID- 1349629
TI  - Intra- and inter-individual variation of background and radiation-induced
      micronucleus frequencies in human lymphocytes.
AB  - Serial blood samples were taken from four healthy individuals (three males, one
      female, aged between 26 and 51 years) in 3-monthly intervals during 1 year.
      Leucocyte suspensions were prepared and exposed to 3 Gy of 137Cs gamma-rays or
      left unirradiated as controls. In a cytokinesis-blocked (CB) micronucleus (MN)
      assay significant inter- and intra-donor variations of background and radiation
      induced MN incidences became apparent. The two sources of variation lead to an
      extra variance sigma I2, in addition to the sample variance sigma e2 of MN
      incidences. The contributions of the different components to the total variance
      were estimated by means of a variance component model. The deviation sigma I for
      the mean background MN level of 1.53 x 10(-2) MN/CB cell was +/- 0.67 x 10(-2)
      and for the mean radiation-induced MN level of 0.53 MN/CB cell it was +/- 0.10.
      The contribution of the intra-individual variance to sigma I2 was about 50% for
      background MN levels and 75% for radiation-induced MN frequencies. With respect
      to the application of the CB-MN assay as a biological dosimetry system, the
      consequences of the present findings for calibration purposes and low-dose
      estimation are discussed. The calculation of the variance components is explained
      in an appendix, which serves also as an example for the adaptation of analysis of
      variance techniques to the evaluation of data derived from scoring of MN, as well
      as from scoring of metaphase chromosomal aberrations.

PMID- 1349630
TI  - Role of protein kinase-C in thymocyte apoptosis induced by irradiation.
AB  - The role of protein kinase C in radiation-induced death of thymocytes was
      studied. For this purpose murine thymocytes were irradiated and incubated for 6 h
      at 37 degrees C and afterwards the fraction of fragmented DNA was measured.
      Results indicate that radiation-induced DNA fragmentation can be prevented by
      adding the protein kinase C inhibitor H-7 or staurosporine to the thymocytes
      during incubation time. Incubation of irradiated cells with HA-1004, an inhibitor
      of cAMP-dependent protein kinase, with a minor effect on protein kinase C did not
      affect the DNA fragmentation induced by irradiation. Incubation of cells with
      phorboldibutyrate gave a dose-dependent induction of DNA fragmentation. This
      effect can be inhibited by staurosporine. These results suggest that radiation
      induced DNA fragmentation is an active cellular process in which protein kinase C
      plays an important role.

PMID- 1349631
TI  - Effects of cycloheximide and actinomycin D on radiation-induced apoptotic cell
      death in the developing mouse cerebellum.
AB  - Effects of cycloheximide and actinomycin D on radiation-induced cell death in the
      external granular layer (EGL) of the cerebellum were studied in vivo. Newborn
      mice were exposed to 0.24 Gy gamma-radiation, and dying cells which exhibited
      pyknosis of nuclei in the EGL were examined at various post-irradiation periods.
      The number of pyknotic cells began to increase 3 h after irradiation, reached a
      peak incidence at 6 h, and then gradually fell to the sham-irradiated level by 18
      h. When pups were injected with cycloheximide 1 h after irradiation, cell death
      was suppressed for 6 h, but a peak mortality as high as in the case of radiation
      alone was attained at 15 h after irradiation. When pups were treated with
      cycloheximide twice, at 1 and 6 h after irradiation, cell death did not occur for
      15 h, but then the incidence rose to a level similar to that after irradiation
      alone. These findings showed that radiation-induced cell death in the EGL is
      suppressed by cycloheximide until the chemical is metabolized. Hence, death is by
      apoptosis which is known to require macromolecular synthesis, and the 'signal'
      for apoptosis in the cell persists for at least 15 h after irradiation. On the
      other hand, actinomycin D injected immediately before or after irradiation did
      not affect the initiation of cell death; actinomycin D alone induced cell death.

PMID- 1349632
TI  - High radiosensitivity of the mineralization capacity of adult murine bone marrow
      in vitro to continuous alpha-irradiation compared to acute X-irradiation.
AB  - Adult BALB/c mice, injected with osteosarcomogenic amounts of 241Am (between 40
      and 500 Bq/g mouse) showed an impaired mineralization capacity of their femoral
      bone marrow. This effect persisted until at least 1 year after 241Am injection
      and was expressed after incubation of bone marrow cells in vitro in conditions
      allowing osteogenic differentiation. The mineralization capacity of marrow in
      vitro was evaluated by measurement of 85Sr uptake from the tissue culture medium.
      Two osteogenic assays were used: in marrow cultured as an intact organ (marrow
      organ cultures), reduced mineralization was observed in mice given 149 Bq 241Am/g
      mouse or more (skeletal dose rate of 25 mGy/day), in stromal marrow cells
      cultured from adherent cell layers and subsequently brought into a three
      dimensional (3D) mineralizing condition (stromal 3D cultures), reduced 85Sr
      uptake was observed from the lowest dose level tested (42 Bq 241Am/g mouse,
      skeletal dose rate of 7 mGy/day). Taking into account that only a fraction of the
      skeletal alpha-dose reached the marrow of the femoral diaphyses, marrow organ
      cultures and stromal 3D cultures exhibited high radiosensitivity to alpha
      irradiation in vivo. However, after acute X-irradiation of marrow in vivo or in
      vitro prior to initiation of the marrow organ cultures, X-ray doses of 4 Gy or
      higher were needed to significantly impair the mineralization capacity of marrow
      organ cultures in vitro. Our data demonstrated that the osteogenic cells from the
      bone marrow are subjected to long-term damage after low doses of continuous alpha
      irradiation in vivo.

PMID- 1349633
TI  - Accumulation of glycosaminoglycans in radiation-induced muscular fibrosis.
AB  - The content and biosynthesis of glycosaminoglycans (GAGs) were studied in the pig
      thigh muscle after acute local gamma-irradiation. Seven months following
      irradiation, the muscular tissue next to the irradiation cone was replaced by
      severe mutilating fibrosis delimited by an intermediary perifbrotic zone.
      Fibrosis, perifibrotic tissue and normal muscle, were sampled and incubated with
      [3H]glucosamine and [35S]sulphate, and GAGs were isolated following pronase
      digestion. Results showed a parallel increase of collagen and GAG content in
      perifibrotic and fibrotic tissues. Sulphated GAGs, heparan sulphate and dermatan
      sulphate were preferentially accumulated in fibrotic tissue, while the hyaluronic
      acid content increased only slightly. Synthesis of sulphated GAGs was more
      elevated in fibrotic tissue than in perifibrotic zone as compared with normal
      muscle. Seven months after irradiation well-developed fibrotic tissue continued
      to synthesize and to accumulate extracellular matrix macromolecules, indicating
      the invasive aspect of post-irradiation fibrosis.

PMID- 1349634
TI  - Radioprotective effect of exogenous glutathione on rat parotid glands.
AB  - The prophylactic effect of glutathione (GSH) on radiation injury in rat parotid
      glands was investigated. GSH was administered to male Wistar rats i.p. 15 min
      prior to irradiation. The necrosis index (NI) of the glands was determined
      histologically 24 h after a single dose of 15, 30, or 60 Gy. Total amylase
      activity, total protein content and wet weight of the glands were measured 30, 60
      and 90 days after irradiation. Administration of GSH prior to radiation minimized
      acute and chronic radiation injuries as a function of the GSH dose: i.e.
      reduction of NI and prevention of the decrease in total amylase activity, total
      protein content and gland weight. The intraglandular level of non-protein-bound
      thiols (NPSH) and GSH increased significantly after i.p. administration of GSH,
      whether or not the glands were irradiated. An autoradiographic study revealed
      that i.p.-administered 35S-GSH was actively taken up by the glandular parenchyma,
      especially in the acini and ducts. It was shown that elevation of the
      intraglandular level of NPSH after exogenous administration of GSH protected the
      parotid glands from radiation injury in the rat.

PMID- 1349635
TI  - Kinetics of depopulation, repopulation and host cell infiltration in the
      rhabdomyosarcoma R1H after 14 MeV neutron irradiation.
AB  - The kinetics of depopulation and repopulation of the solid transplantable
      rhabdomyosarcoma R1H in the rat was studied following irradiation with 5 Gy of 14
      MeV neutrons. Several parameters were sequentially measured over a time period of
      4 weeks after irradiation: the tumour volume was assessed by in situ caliper
      measurements; the numerical density of tumour cells was obtained by morphometry;
      the clonogenic fraction of tumour cells was derived from in vitro colony assay;
      and the numerical ratio of host to tumour cells was determined by flow cytometry.
      From these primary parameters the number of clonogenic tumour cells, non
      clonogenic tumour cells, and nucleated host cells per tumour, as well as their
      variation with time, were derived. The results were compared with two sets of
      data obtained previously for the same tumour exposed to 15 Gy of 200 kVp X-rays.
      Survival of tumour cells was reduced to 5.5 +/- 0.5% by 5 Gy neutrons and to 4.5
      +/- 0.5% by 15 Gy X-rays, i.e. an RBE of close to 3. There was a lag period
      before the onset of repopulation (4.9 +/- 0.4 days and 4.9 +/- 0.5 days,
      respectively), followed by a high initial rate of repopulation corresponding to a
      doubling time of 2.0 +/- 0.2 days for neutrons and 2.1 +/- 0.2 days for X-rays.
      The rate of depopulation was significantly different for the two treatment
      modalities; the halving time for the number of non-clonogenic tumour cells was 11
      +/- 4 days for neutrons and 2.8 +/- 0.5 days for X-rays.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1349636
TI  - Excitatory postsynaptic potentials recorded from regular-spiking cells in layers
      II/III of rat sensorimotor cortex.
AB  - 1. Intracellular recording techniques were used to investigate the physiological
      and pharmacological properties of stimulus-induced excitatory postsynaptic
      potentials (EPSPs) recorded in regular-spiking cells located in layers II/III of
      rat sensorimotor cortical slices maintained in vitro. 2. Depending on the
      strength of the extracellular stimuli, a pure EPSP or an EPSP-inhibitory
      postsynaptic potential sequence was observed under perfusion with normal medium.
      The EPSPs displayed short latency of onset [2.4 +/- 0.7 (SD) ms] and were able to
      follow repetitive stimulation (tested less than or equal to 5 Hz). Variation of
      the membrane potential (Vm) revealed two types of voltage behavior for the short
      latency EPSP. The first type decreased in amplitude with depolarization and
      increased in amplitude with hyperpolarization. In contrast, the second type
      behaved anomalously by increasing and decreasing in size after depolarization and
      hyperpolarization, respectively. 3. Several experimental procedures were carried
      out to investigate the mechanism underlying the anomalous voltage behavior of the
      EPSP. Results indicated that this type of Vm dependency could be mimicked by an
      intrinsic response evoked by a brief pulse of depolarizing current and could be
      abolished by N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (50
      mM). Furthermore, the EPSP was not sensitive to the N-methyl-D-aspartate (NMDA)
      receptor antagonist 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP,
      10 microM). Thus the anomalous voltage relationship of the neuronal membrane. 4.
      The involvement of non-NMDA receptors in excitatory synaptic transmission was
      investigated with their selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX, 1-10 microM). This drug greatly reduced or completely blocked the EPSP in
      a dose-dependent manner (1-10 microM). The IC50 for the CNQX effect was
      approximately 2 microM. In the presence of CNQX (10 microM) and glycine (10
      microM), synaptic stimulation failed to elicit firing of action potential.
      However, a CPP-sensitive EPSP was observed. 5. When synaptic inhibition was
      reduced by low concentration of bicuculline methiodide (BMI, 1-2 microM),
      extracellular stimulation revealed late EPSPs (latency to onset: 10-30 ms) that
      were not discernible in normal medium. Similar to the short-latency EPSP, the Vm
      dependency displayed by this late EPSP could be modified by inward membrane
      rectifications. The late EPSP appeared to be polysynaptic in origin because 1)
      its latency of onset was long and variable and 2) it failed to follow repetitive
      stimuli delivered at a frequency that did not depress the short-latency
      EPSP.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1349637
TI  - Identified FMRFamide-immunoreactive neuron LPL16 in the left pleural ganglion of
      Aplysia produces presynaptic inhibition of siphon sensory neurons.
AB  - The gill- and siphon-withdrawal reflex of Aplysia undergoes transient inhibition
      following noxious stimuli such as tail shock. This behavioral inhibition appears
      to be due in part to transient presynaptic inhibition of the siphon sensory
      cells, which can be mimicked by application of the peptide FMRFamide. Although
      FMRFamide is widespread in the Aplysia nervous system, an FMRFamide-containing
      inhibitory neuron has not previously been identified. We have searched for such a
      neuron by combining FMRFamide immunofluorescence with fluorescent dye backfilling
      from the abdominal ganglion, the location of the siphon sensory cells. These
      methods localized a neuron in the left pleural ganglion, which we have named
      LPL16. LPL16 is FMRFamide immunoreactive; it is excited by tail shock; and
      stimulation of LPL16 produces inhibition of siphon sensory cell-to-motor cell
      postsynaptic potentials and narrowing of action potentials in the sensory cells
      in tetraethylammonium solution. These results indicate that LPL16 participates in
      the inhibitory effects of tail shock, and support the idea that FMRFamide plays a
      physiological role in the inhibition.

PMID- 1349639
TI  - Direct in vitro electrochemical measurement of dopamine overflow in intermediate
      pituitary: characterization and pharmacology.
AB  - The intermediate lobe of the pituitary (IL) is a promising model system for the
      study of dopaminergic neurotransmission. We sought to characterize the release of
      dopamine (DA) from the IL using electrochemical methods which provide increased
      spatial and temporal resolution compared to the superfusion techniques which had
      previously been employed to study this system. After pretreatment with monoamine
      oxidase (MAO) inhibitors, we were able to routinely measure DA overflow after 30
      sec, 9-Hz electrical stimulation of the pituitary stalk. This effect was blocked
      by tetrodotoxin and Cd++ ions confirming that it was due to synaptic activation.
      Intracellular recording from the postsynaptic cells (melanotrophs) showed a
      postsynaptic hyperpolarization with a time course that was identical to that of
      DA overflow. Overflow was increased and prolonged by agents that inhibited DA
      uptake (nomifensine, mazindol or cocaine) and increased but not prolonged by a D2
      antagonist (sulpiride), presumably acting via presynaptic autoreceptors. The DA
      precursor 3,4-dihydroxyphenylalanine also increased DA overflow gradually over a
      45-min time period. In view of reports of possible colocalization of DA and gamma
      aminobutyric acid in IL, we determined the possible effects of GABAergic agents
      on DA release. Neither agonists (muscimol or baclofen) nor antagonists
      (bicuculline or 2-hydroxysaclofen) had any effect on DA overflow. By using the
      MAOA-specific inhibitor clorgyline and the MAOB-specific inhibitor deprenyl we
      were able to confirm that the MAOA form of the enzyme is involved in DA
      metabolism in this preparation.

PMID- 1349638
TI  - Glutamate-induced calcium transient triggers delayed calcium overload and
      neurotoxicity in rat hippocampal neurons.
AB  - Glutamate-induced changes in intracellular free Ca2+ concentration ([Ca2+]i) were
      recorded in single rat hippocampal neurons grown in primary culture by employing
      the Ca2+ indicator indo-1 and a dual-emission microfluorimeter. The [Ca2+]i was
      monitored in neurons exposed to 100 microM glutamate for 5 min and for an ensuing
      3 hr period. Ninety-two percent (n = 64) of these neurons buffered the glutamate
      induced Ca2+ load back to basal levels after removal of the agonist; thus, the
      majority of cells had not lost the ability to regulate [Ca2+]i at this time.
      However, following a variable delay, in 44% (n = 26) of the neurons that buffered
      glutamate-induced Ca2+ loads to basal levels, [Ca2+]i rose again to a sustained
      plateau and failed to recover. The changes in [Ca2+]i that occur during glutamate
      induced delayed neuronal death can be divided into three phases: (1) a triggering
      phase during which the neuron is exposed to glutamate and the [Ca2+]i increases
      to micromolar levels, followed by (2) a latent phase during which the [Ca2+]i
      recovers to a basal level, and (3) a final phase that begins with a gradual rise
      in the [Ca2+]i that reaches a sustained plateau from which the neuron does not
      recover. This delayed Ca2+ overload phase correlated significantly with cell
      death. The same sequence of events was also observed in recordings from neuronal
      processes. The delayed Ca2+ increase and subsequent death were dependent upon the
      presence of extracellular Ca2+ during glutamate exposure. Calcium influx during
      the triggering phase resulted from the activation of both NMDA and non-NMDA
      receptors as indicated by studies using receptor antagonists and ion
      substitution. Treatment with TTX (1 microM) or removal of extracellular Ca2+ for
      a 30 min window following agonist exposure failed to prevent the delayed Ca2+
      overload. The delayed [Ca2+]i increase could be reversed by removing
      extracellular Ca2+, indicating that it resulted from Ca2+ influx. The three
      phases defined by changes in the [Ca2+]i during glutamate-induced neuronal
      toxicity suggest three distinct targets to which neuroprotective agents may be
      directed.

PMID- 1349641
TI  - Increased rates of punished responding produced by buspirone-like compounds in
      rats.
AB  - Buspirone has been reported to have effects on punished responding in rats which
      are considerably smaller and less reliable than those produced by
      benzodiazepines. A recent study, however, found that buspirone and ipsapirone
      increased operant responding suppressed by a stimulus which preceded unavoidable
      shock, suggesting that conditioned emotional response protocols may be more
      sensitive than punishment procedures. This hypothesis was not supported by the
      results of the present study. The food-reinforced lever pressing of rats was
      maintained by a multiple VI schedule with punished and unpunished components. The
      experimental parameters were similar to those used in the previous conditioned
      emotional response study. The benzodiazepines, chlordiazepoxide and clorazepate,
      as well as buspirone (at one dose) and ipsapirone (at several doses), increased
      rates of punished responding. The 5-hydroxytryptamine-1A receptor ligands 8
      hydroxy-2-(di-n-propylamino)tetralin and MDL 73005EF did not reliably produce
      similar effects, although increased rates of punished responding were seen in
      some animals. Haloperidol, imipramine and idazoxan did not increase punished
      response rates. Although the increases in punished responding produced by
      buspirone were smaller than those produced by chlordiazepoxide and clorazepate,
      the effect of ipsapirone was quantitatively similar to that of the
      benzodiazepines.

PMID- 1349640
TI  - Effects of 3,4-dihydroxymethamphetamine and 2,4,5-trihydroxymethamphetamine, two
      metabolites of 3,4-methylenedioxymethamphetamine, on central serotonergic and
      dopaminergic systems.
AB  - The effects of 3,4-dihydroxymethamphetamine (DHM) and 2,4,5
      trihydroxymethamphetamine (THM) on central serotonergic and dopaminergic systems
      were investigated to determine if these metabolites share the neurochemical
      properties of 3,4-methylenedioxymethamphetamine. THM (50-200 micrograms) or DHM
      (135 micrograms) was administered i.c.v. to rats; 5 days later, cortical,
      striatal and hippocampal tryptophan hydroxylase (TPH) activity were decreased by
      THM in a dose-dependent manner, whereas DHM was without effect in these brain
      structures. The concentration of serotonin in the brain structures contralateral
      to the side of THM injection was also decreased, but to a lesser degree. THM (100
      and 200 micrograms) increased TPH activity to 155% of control in the dorsal
      raphe, whereas a dose of 50 micrograms increased TPH activity to 132% of control
      in the median raphe nucleus. THM also markedly reduced striatal tyrosine
      hydroxylase activity, but did not alter enzyme activity in the substantia nigra;
      DHM increased striatal tyrosine hydroxylase activity to 115% of control. These
      results suggest that THM, but not DHM, is toxic to both dopaminergic and
      serotonergic nerve terminals. Although THM could not be established as the
      neurotoxic metabolite explaining 3,4-methylenedioxymethamphetamine (MDMA)
      toxicity, its properties may prove useful in elucidating amphetamine toxicity.

PMID- 1349642
TI  - Use of 2-hydroxypropyl-beta-cyclodextrin as an intrathecal drug vehicle with
      opioids.
AB  - 2-Hydroxypropyl-beta-cyclodextrin (CDEX), a seven-membered glucose pyranose
      structure, forms reversible inclusion complexes with the lipophilic portion of a
      drug molecule by noncovalent bonding. This can increase the water solubility of
      lipid-soluble drugs and reduce the rate of clearance of such agents from the
      spinal cord into the vasculature after i.t. administration. In this study,
      opioids (morphine, lofentanil, alfentanil and sufentanil) with and without CDEX
      (20, 2, 0.2 and 0.02% w/v in sterile water) were administered spinally in rats
      prepared with chronic i.t. catheters. CDEX prolonged the duration of analgesia
      (52.5 degrees C hot plate) and reduced the incidence of catalepsy otherwise
      produced by a supermaximal i.t. dose of each of the opioids. The magnitude of the
      potentiating effect of CDEX on opioids was dependent upon concentration of the
      CDEX and varied with drug lipid partition coefficients. The highest concentration
      of CDEX alone (20%) had no effect upon the volume-evoked micturition reflex,
      blood pressure, heart rate, or spinal reflexes. Our data indicate that CDEX may
      be a useful i.t. vehicle for modifying the redistribution characteristics of
      highly diffusible molecules after their i.t. administration, and that for each
      drug there is an optimal CDEX concentration. In the present case, CDEX prolongs
      the spinal analgesic action and reduces the supraspinal actions of i.t. drugs.

PMID- 1349643
TI  - Perinatal changes in the coupling of beta 1- and beta 3 adrenergic receptors to
      brown fat adenylyl cyclase.
AB  - The stimulation of adenylyl cyclase by catecholamines in neonatal brown adipose
      tissue (BAT) is markedly biphasic, suggesting the existence of receptors that
      have both high and low affinities for catecholamines. The identities of these
      receptors were examined by comparing responses in neonatal BAT membranes to those
      of Chinese hamster ovary cells which had been transfected to express the cloned
      rat beta 1 and beta 3 receptors. The results from these experiments indicate that
      high-affinity stimulation of adenylyl cyclase by catecholamines in BAT is
      mediated by beta 1 receptors, as evidenced by the potencies of norepinephrine and
      isoproterenol at this receptor and the potent blockade of the receptor by
      alprenolol. The low-affinity catecholamine receptor appears to be the beta 3
      receptor, as indicated by the low potency of catecholamine agonists and the
      inability of low concentrations of alprenolol to block this activity.
      Furthermore, this receptor, like the cloned rat beta 3 receptor, was antagonized
      by (-)-4-(3-t-butylamino-2-hydroxypropoxy)benzimidazol-2-one (CGP 12177) and was
      stimulated by (R',R')-4-(2-[(2[(3-chlorophenyl)-2-
      hydroxyethyl]amino)propyl]phenyl)phenoxyacetic acid (BRL 37344). These results
      indicate that both beta 1 and beta 3 receptors couple to adenylyl cyclase in BAT
      and that activation of adenylyl cyclase in neonatal BAT is mediated primarily by
      beta 3 receptors. Beta 3 receptors were also clearly detected in weanling BAT
      with the beta 3-selective agonist BRL 37344. However, when catecholamines were
      used to stimulate activity, the activation of adenylyl cyclase by beta 1
      receptors, which occurred at low concentrations of catecholamines, obscured the
      activation of adenylyl cyclase by beta 3 receptors, which occurred only at high
      concentrations.

PMID- 1349644
TI  - Effects of agonist exposure on the coupling of beta 1 and beta 3 adrenergic
      receptors to adenylyl cyclase in isolated adipocytes.
AB  - The coupling of beta 1 and beta 3 adrenergic receptors to adenylyl cyclase was
      examined in membranes of isolated white adipocytes. The activation of adenylyl
      cyclase by isoproterenol (ISO) was biphasic. The high-affinity activation of
      adenylyl cyclase, which occurred at submicromolar concentrations of ISO, was
      mediated by beta 1 receptors, whereas low-affinity activation was mediated by
      beta 3 receptors. The relative activation of adenylyl cyclase by beta 3 receptors
      was less when ISO was used to stimulate activity, compared to when the beta 3
      selective agonist BRL 37344 was used. These data indicate that both receptor
      subtypes can stimulate the same adenylyl cyclase in membranes of control cells,
      and that the activation of adenylyl cyclase by beta 1 receptors by low
      concentrations of catecholamines can obscure the activation by beta 3 receptors
      by high concentrations of catecholamines. Exposure of adipocytes to ISO at
      concentrations that either selectively stimulate beta 1 receptors or
      nonselectively stimulate both beta receptor subtypes greatly decreased the
      ability of beta 1, but not beta 3, receptors to activate adenylyl cyclase. In
      contrast, the exposure of cells to the beta 3-selective agonist BRL only slightly
      desensitized beta 1 receptors and did not affect beta 3 receptor activation of
      adenylyl cyclase. These data indicate that acute agonist exposure desensitizes
      beta 1, but not beta 3, receptors.

PMID- 1349646
TI  - Hepatic cytochrome P-450-mediated activation of rat aortic guanylyl cyclase by
      glyceryl trinitrate.
AB  - Previous studies have demonstrated hepatic cytochrome P-450-dependent
      biotransformation of organic nitrates. We assessed whether this biotransformation
      resulted in the formation of an activator of guanylyl cyclase using the 100,000 x
      g supernatant of rat aorta as a source of crude enzyme. Incubation of aortic
      supernatant with rat hepatic microsomes and glyceryl trinitrate (GTN) resulted in
      concentration-dependent increases in guanylyl cyclase activity provided that the
      incubations were performed anaerobically and that reduced nicotinamide adenine
      phosphate was added. Cysteine-dependent activation of guanylyl cyclase by GTN was
      greater under anaerobic compared to aerobic conditions. Guanylyl cyclase
      activation by GTN was increased using hepatic microsomes from phenobarbital
      treated but not beta-naphthoflavone (BNF)-treated rats and was decreased when
      microsomes from cimetidine-treated rats were used. The hepatic microsome
      dependent activation of guanylyl cyclase by GTN was inhibited by in vitro
      treatment of microsomes with carbon monoxide, SKF 525A, metyrapone and
      cimetidine, but not by ranitidine. The sensitivity of isolated rat aorta to the
      relaxant effects of GTN was increased under low oxygen conditions or when aortae
      were obtained from phenobarbital- or beta-naphthoflavone-treated rats. Treatment
      of rats with cimetidine did not affect GTN-induced relaxation. The vascular
      biotransformation of GTN was increased greater than 3-fold when performed
      anaerobically, and this increase was prevented by pretreatment of the tissues
      with carbon monoxide. Together, these data provide strong evidence for the
      involvement of hepatic cytochromes P-450 in the formation from GTN of an
      activator of guanylyl cyclase (presumably NO or some closely related compound),
      and suggest that at least a portion of the vascular biotransformation of GTN is
      mediated by hemoproteins.

PMID- 1349645
TI  - Centrally mediated cardiovascular actions of dynorphin A(1-8) on rat hippocampal
      formation.
AB  - The effects of dynorphin A(1-8) (DA1-8) microinjected into various areas of the
      hippocampal formation (HF) on the mean blood pressure (MBP) and heart rate (HR)
      were investigated in the alpha-chloralose-anesthetized rat. Intra-HF injection of
      DA1-8 dose-dependently (0.5-50 nmol) reduced MBP and HR. Depressor and
      bradycardic responses also occurred following microinjection of the excitatory
      amino acid l-glutamate (1 M, 0.2-0.4 microliter) into the DA1-8-sensitive sites.
      By contrast, administration of 4% lidocaine (0.2-0.4 microliter) into the same HF
      sites failed to affect MBP and HR. Pretreatment of the HF with the kappa opioid
      receptor antagonist nor-binaltorphimine at a dose of 2 to 4 nmol, which itself
      had no significant influence on basal MBP and HR, almost totally abolished the
      depressor and bradycardic responses induced by HF injection of DA1-8. DA1-8 at a
      dose of 10 nmol produced no significant alterations in the frequency of
      respiration and blood PaO2 and PaCO2 and artificial ventilation did not change
      the cardiovascular responses of DA1-8. Atropine given i.v. almost totally
      eliminated the bradycardia and partially prevented the hypotensive responses to
      intra-HF DA1-8. The data indicate that exogenous administration of DA1-8 into the
      HF is capable of producing substantial inhibition of peripheral cardiovascular
      function. Because lidocaine was without effect, the hypotension and bradycardia
      most likely resulted from an augmentation of an excitatory process rather than
      from direct inhibition of hippocampal neurons around the injection sites. The
      effects appear to involve activation of kappa opioid receptors.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1349647
TI  - Alpha adrenoceptor subtypes involved in the emetic action in dogs.
AB  - In order to assess the involvement of alpha-1 and alpha-2 adrenoceptors in
      emesis, the emetic effect of eight alpha agonists was studied in dogs. The i.m.
      administration of each agonist elicited dose-dependent emesis. The order of
      potency in inducing emesis was: clonidine greater than oxymetazoline greater than
      tramazoline greater than naphazoline greater than xylazine greater than
      epinephrine greater than methoxamine = phenylephrine. The clonidine-induced
      emesis was antagonized by adrenoceptor antagonists showing alpha-2 blocking
      activity, yohimbine, tolazoline and phentolamine. Among these antagonists,
      yohimbine was the most effective. The alpha-1 and beta adrenergic, cholinergic,
      dopaminergic, histaminergic, serotonergic and opioid receptor antagonists did not
      prevent the clonidine-induced emesis. The emesis induced by oxymetazoline,
      tramazoline, xylazine, naphazoline and epinephrine was also antagonized by a
      selective alpha-2 adrenoceptor antagonist, yohimbine, but not by a selective
      alpha-1 adrenoceptor antagonist, prazosin. In contrast, methoxamine and
      phenylephrine-induced emesis was antagonized by prazosin, but not by yohimbine.
      Neither yohimbine nor prazosin prevented the morphine- and histamine-induced
      emesis. These results indicate that alpha-2 adrenoceptors are involved in the
      mediation of emetic action, and that the alpha adrenoceptor-mediated emesis does
      not involve beta adrenergic, cholinergic, dopaminergic, histaminergic,
      serotonergic and opioid receptors in the emetic pathway. This study further
      suggests that alpha adrenoceptors involved in the emesis are mainly of the alpha
      2 type, although the involvement of alpha-1 adrenoceptors cannot be ruled out.

PMID- 1349650
TI  - Notes from the American Society of Anesthesiologists annual meeting.

PMID- 1349649
TI  - Microinjection of the D2 agonist quinpirole into the A10 dopamine region blocks
      amphetamine-, but not cocaine-stimulated motor activity.
AB  - Dopamine neurons in the ventral mesencephalon are under the inhibitory influence
      of dopamine D2 and gamma-aminobutyric acidB receptors. In a previous report, we
      demonstrated that intra-A10 injections of baclofen, a gamma-aminobutyric acidB
      agonist, could inhibit the motor-stimulant response to cocaine and amphetamine.
      In order to further extend these results, we examined the effects of injection of
      the D2 agonist quinpirole into the A10 region on cocaine- and amphetamine
      stimulated motor activity. The results of this study showed that intra-A10
      quinpirole dose-dependently decreased locomotor activity. In addition, an intra
      A10 injection of 0.3 nmol/microliter quinpirole, a dose chosen for its near
      threshold effect, could block the motor-stimulant response to a low dose of
      amphetamine (0.5 mg/kg) and attenuate the response to moderate doses (1.0 and 2.0
      mg/kg). Cocaine-stimulated motor activity, at all doses tested (7.5, 15.0 and
      30.0 mg/kg), was not altered by intra-A10 quinpirole pretreatment. In vivo
      microdialysis revealed that quinpirole was unable to block the amphetamine
      induced increase in extracellular dopamine concentrations within the nucleus
      accumbens, despite blocking the motor-stimulant response. It is suggested that
      the different mechanisms of action of cocaine and amphetamine, uptake blocker vs.
      releaser or longloop vs. shortloop feedback inhibition of A10 dopamine neurons,
      respectively, may account for the differential effects that quinpirole had in
      blocking the motor-stimulant response to these psychostimulants.

PMID- 1349648
TI  - Characterization of the pharmacology of intrathecally administered alpha-2
      agonists and antagonists in rats.
AB  - To examine the pharmacology of the spinal alpha receptor which modulates
      nociceptive transmission, the antinociceptive effects (52.5 degrees C hot plate;
      HP) of three i.t. administered alpha-2-preferring agonists [dexmedetomidine
      (DMET); clonidine (CLON) and ST-91] were determined. The antagonist potency of
      atipamezole (ATI), idazoxan (IDAZ), yohimbine (YOH) and prazosin (PRA),
      adrenergic antagonists with differing alpha-2-preferring profiles, were then
      examined for each of the three agonists. The three agonists produced a dose
      dependent block of the HP response with the ED50 and the dose which was just
      maximally effective being DMET (3.2 and 10 micrograms); CLON (27 and 100
      micrograms) and ST-91 (6.1 and 20 micrograms). After determining the time of peak
      antagonist effect, studies were run in which the just maximally effective dose of
      each agonist was given in conjunction with one of several doses of the several
      antagonists. The rank order of potency (and ID50 in microgram) for the several
      antagonists against each of the three agonists was: DMET = [IDAZ (1.9); ATI
      (4.1); YOH (70); PRA (greater than 100)]; CLON = [ATI (2.7); IDAZ (23); YOH (52);
      PRA (greater than 100)]; ST-91 = [PRA (38); YOH (69); ATI (greater than 100);
      IDAZ (greater than 100)]; where antagonists joined by a common line display
      overlapping 95% confidence intervals and greater than (greater than) indicates
      failure to achieve a 50% reversal at the highest antagonist dose.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1349651
TI  - Dangerous consequences: neuroleptic-induced tardive akathisia.

PMID- 1349652
TI  - Neuronal origins of K(+)-evoked amino acid release from cerebellar cultures.
AB  - Neuronal cultures from rat cerebellum consisting of approximately 90%
      glutamatergic granule neurons, 5-7% GABAergic inhibitory interneurons, and 3-5%
      glial cells, were treated for four days with 50 microM kainic acid (KA) to
      determine the cellular origin of released endogenous neuroactive substances. KA,
      known to be selectively toxic to GABAergic neurons, caused an estimated 80%
      decrease in glutamic acid decarboxylase (GAD) immunofluorescence. Furthermore,
      K(+)-stimulated release of GABA decreased to 20% of control values, and did not
      return to control levels in cultures "recovered" two days in KA-free media,
      suggesting the loss of inhibitory interneurons. Similarly, adenosine and taurine
      showed decreased K(+)-stimulated release, which was unrecoverable when KA was
      removed from the medium. K(+)-stimulated release of glutamate and aspartate also
      decreased by 50% and 70%, respectively, after chronic KA treatment. In contrast,
      however, this release returned to control levels in recovered cultures. All
      decreases in K(+)-stimulated release were prevented by concurrent treatment with
      KA and the KA antagonist 6-cyano-6-nitroquinoxaline-2,3-dione (CNQX), indicating
      that a receptor-mediated mechanism was involved. We conclude that, in these
      cultures, most of the K(+)-stimulated release of adenosine and taurine originates
      from the GABAergic interneurons, the basket and stellate cells, which are
      selectively killed by the KA treatment. The data also strongly suggest that
      glutamate and aspartate, the levels of which recover after KA treatment,
      originate mainly from the granule neurons.

PMID- 1349653
TI  - Pharmacologic attenuation of the sympathetic response; impact on cardiac
      morbidity in vascular surgical patients.

PMID- 1349655
TI  - Which antihypertensive drugs first--and why!

PMID- 1349654
TI  - Effects of disease stage and zidovudine therapy on the detection of human
      immunodeficiency virus type 1 in semen.
AB  - OBJECTIVE: To determine the prevalence and temporal expression of infectious
      human immunodeficiency virus type 1 (HIV-1) in the semen of HIV-1 seropositive
      men and to determine whether the detection of HIV-1 in semen is associated with
      disease stage, zidovudine treatment status, or other clinical factors. DESIGN: A
      microculture technique was used to detect infectious HIV-1 in semen from a cohort
      of 95 seropositive men. In addition, semen cultures were performed monthly for at
      least 6 months for 14 of the men. Information was obtained by interview and
      extracted from medical records to identify clinical variables associated with HIV
      1 in semen. PATIENTS: Sixty HIV-1 seropositive homosexual men participating in
      clinical studies at the Fenway Community Health Center, Boston, Mass, and 35 HIV
      seropositive bisexual or heterosexual men participating in the California Partner
      Study of the University of California, San Francisco. MAIN OUTCOME MEASURES:
      Semen HIV-1 culture results, seminal leukocyte counts, Centers for Disease
      Control (CDC) disease stage, peripheral CD4+ cell counts, zidovudine therapy, HIV
      risk category. RESULTS: In the cross-sectional study, HIV-1 was cultured from the
      semen of nine (9%) of 95 men. Factors associated with detection of HIV-1 in semen
      were peripheral CD4+ cell counts of 0.20 x 10(9)/L (200/microL) or less (adjusted
      odds ratio [OR], 23.33; 95% confidence interval [Cl], 2.89 to 175.63);
      symptomatic (CDC class IV) disease (adjusted OR, 6.56; 95% Cl, 1.02 to 66.76);
      and seminal leukocytosis (greater than 1 x 10(9) white blood cells per liter of
      semen) (adjusted OR, 7.02; 95% Cl, 1.28 to 39.29). Zidovudine therapy was
      associated with decreased detection of HIV-1 in semen (adjusted OR, 0.04; 95% Cl,
      0.00 to 0.63). In the longitudinal study of 14 men who had neither peripheral
      CD4+ cells counts of 0.20 x 10(9)/L or less nor seminal leukocytosis, seminal HIV
      1 was detected in at least one sample from six men (43%). CONCLUSION: HIV-1 is
      more commonly found in semen from men with advanced HIV-1 infection and seminal
      leukocytosis but can also be cultured from semen of men with neither of these
      conditions. Zidovudine therapy may decrease the prevalence and/or titer of
      seminal HIV-1. However, all HIV-1-infected persons should continue to assume that
      they are potentially infectious through sexual contact.

PMID- 1349656
TI  - [Hemodialysis therapy of malignant hypertension].

PMID- 1349657
TI  - [Growth hormone and prolactin metabolism in chronic renal failure with
      hemodialysis].

PMID- 1349658
TI  - [Dialysis-associated hypertension].

PMID- 1349659
TI  - [Upper gastrointestinal complications in uremic patients with dialysis].

PMID- 1349660
TI  - [Psychiatric complications in hemodialysis patients].

PMID- 1349661
TI  - Fluorogold administration via microdialysis labels neurons terminating within the
      dialysis region.
AB  - The use of microdialysis to monitor the release of neurotransmitters in selected
      regions of the CNS has increased substantially in the last several years. We
      describe here a method for retrogradely labeling neurons that terminate within
      the effective sampling region surrounding the dialysis cannula. This is
      accomplished by direct infusion of fluorogold through the dialysis cannula. By
      combining this technique with immunohistochemistry, it is possible to identify
      neurons that could contribute to the neurotransmitter release measured by
      microdialysis.

PMID- 1349662
TI  - The treatment of hairy cell leukemia: an update.
AB  - The treatment of hairy cell leukemia (HCL) requires continuing update. The role
      for splenectomy is extremely limited. Alfa-interferon therapy has been available
      and utilized for five years; there have been few complete remissions. The
      experience with Pentostatin has resulted in a majority of clinical complete
      remissions after several months of therapy, but persistence of a small percentage
      of hairy cells in the bone marrow. The most recent therapeutic agent, 2-chloro
      deoxyadenosine (2-CDA) is given for seven days and results in a complete
      remission in the great majority of patients with no evidence of persistent bone
      marrow disease. If this trend persists, 2-CDA will become first line therapy for
      HCL as it may cure the disease.

PMID- 1349663
TI  - [1.2 millions of Europeans were killed by tobacco in 1990].

PMID- 1349664
TI  - [Intrauterine transplantation with fetal stem cells cures fetal diseases].

PMID- 1349665
TI  - [Genotyping for drug metabolism capacity can give valuable clinical information].
AB  - There is pronounced individual variation in the human metabolism (eg, acetylation
      and hydroxylation) of drugs, in many cases due to genetic factors. The genetic
      basis of cytochrome P4502D6 gene defects has recently been elucidated, for
      instance. The cytochrome P4502D6 is absent from 7 percent of the Caucasian
      population, usually owing to the presence of either of two different mutations in
      the corresponding gene. PCR amplification of genomic DNA with allele-specific
      primers enables rapid prediction of the patient's drug metabolism capacity and
      the individualization of drug treatment with respect to dosage.

PMID- 1349666
TI  - Value of axillary dissection in addition to lumpectomy and radiotherapy in early
      breast cancer. The Breast Carcinoma Collaborative Group of the Institut Curie.
AB  - Axillary dissection in early breast cancer remains controversial because of its
      substantial side-effects and because its value with respect to recurrence or
      survival has not been unequivocally proven. Between 1982 and 1987, 658 patients
      were included in a prospective randomised comparison of lumpectomy alone with
      lumpectomy plus axillary dissection. All patients had a unilateral breast tumour
      not exceeding 3 cm in diameter and lymph-node involvement or metastases.
      Radiation therapy was given to both groups. The two groups of patients were
      similar with respect to mean age, TNM stage, and presence of hormonal receptors.
      Median follow-up was 54 months. 5-year survival of the patients was 94.2% (95%
      Cl: 92.1-96.4). There was a significant advantage in survival in the axillary
      dissection group (p = 0.014). Recurrence of tumour in the breast was similar in
      the two groups but visceral metastases, supraclavicular metastases, and lymph
      node recurrences were less frequent in the axillary dissection group. Survival
      was related to the age of the patients (p = 0.005), the presence of positive
      nodes (p = 0.006), the histological grading (p less than 0.0001), and the
      presence of hormonal receptors (progesterone p = 0.0008, oestrogen p less than
      0.0001). Treatment-adjusted relative risk was 2.4 (95% Cl: 1.3-4.2). The findings
      show that axillary dissection is justified for treatment of small breast cancers,
      although whether the better survival is due to axillary clearance itself or to
      adjuvant treatment for lymph-node involvement is unclear.

PMID- 1349667
TI  - Prognostic factors and survival in children with perinatal HIV-1 infection. The
      Italian Register for HIV Infections in Children.
AB  - The signs that may arise after perinatal infection with human immunodeficiency
      virus type 1 (HIV-1) have been classified by the Centers for Disease Control, but
      the clinical usefulness of the classification system and the prognostic
      importance of each disease pattern have not been established. We sought to
      address these issues by analysing data from the Italian Register for HIV
      infection in children. We studied 1887 children born to HIV-1-seropositive
      mothers. 1045 were identified at birth and the others were registered later
      (median age 4.8 [range 0.4-72] months). HIV-1-associated signs developed in 433
      (81.8%) of 529 seropositive infected children at a median age of 5 (0.03-84)
      months. These signs appeared significantly earlier in the 102 children who died
      of HIV-1-related illness than in those who are still alive (median 3 [0.03-55] vs
      6 [0.03-84] months; p less than 0.001). The cumulative proportion surviving at
      age 9 years was 49.5% (95% confidence interval 27-65%) and the median survival
      time was 96.2 months. Separate analysis of the 112 seropositive infected children
      followed from birth and older than 15 months gave similar results. Hepatomegaly,
      splenomegaly, lymphadenopathy, parotitis, skin diseases, and recurrent
      respiratory tract infections formed the mildest disease pattern. Lymphoid
      interstitial pneumonitis and thrombocytopenia were signs of intermediate disease.
      By contrast, in multivariate analysis specific secondary infectious diseases,
      severe bacterial infections, progressive neurological disease, anaemia, and fever
      were significant and independent negative predictors of survival. Growth failure,
      persistent oral candidosis, hepatitis, and cardiopathy were associated in
      univariate analysis with significantly shorter survival. Our findings suggest
      that the outlook for children with perinatal HIV-1 infection is better than
      previously thought and that a new clinical staging system of single disease
      patterns is needed.

PMID- 1349668
TI  - Intensity of reinfection with Ascaris lumbricoides and its implications for
      parasite control.
AB  - Intestinal helminths are among the most common and widespread of human
      infections. Because it is typical to find that most worms are aggregated in a few
      potential hosts it has been suggested that some individuals are predisposed to
      heavy infections and that morbidity could be controlled by the treatment of
      heavily infected individuals only. We have studied the prevalence and intensity
      of reinfection with the intestinal nematode Ascaris lumbricoides among people
      living in Dhaka, Bangladesh. 880 people were treated with pyrantel pamoate three
      times at six month intervals, and on each occasion they collected all their
      stools for 48 h after treatment. Worms expelled by each subject were counted and
      weighed. The prevalence of infection at round 1 of treatment was 89% and the mean
      burden was 18.5 worms. Reinfection was rapid and at rounds 2 and 3 the prevalence
      was 82% and 80%, respectively, with mean burdens of 14.0 and 11.5 worms. The
      intensity of reinfection was not random: more subjects than expected became
      heavily reinfected (greater than or equal to 15 worms) and more subjects than
      expected remained lightly infected (less than or equal to 14 worms) (p less than
      0.001). Worms were highly aggregated at each round of treatment but although just
      over 10% of all subjects were heavily infected at each and every round of
      treatment, over 60% of all subjects were heavily infected at least once. The
      findings show that some individuals seem to be susceptible to heavy infection
      whereas others are not, that deworming has a greater effect on the intensity of
      infection than on the prevalence, and that mass chemotherapy is likely to be a
      more effective means to control morbidity than is selective treatment of heavily
      infected individuals only.

PMID- 1349669
TI  - Effects of insulin-like growth factor on linear growth, head circumference, and
      body fat in patients with Laron-type dwarfism.
AB  - Patients with Laron-type dwarfism are clinically indistinguishable from those
      with isolated growth hormone (GH) deficiency, yet have high circulating GH
      concentrations associated with an inability to generate endogenous insulin-like
      growth factor I (IGF-I). Biosynthetic IGF-I was administered subcutaneously once
      daily for 3 to 10 months to 5 children with Laron-type dwarfism aged 3.3 to 14.5
      years. There was a rapid stimulation of linear growth in body limbs, with a
      striking increase in head circumference, increased body weight, and a reduction
      in subcutaneous fat. Administration of IGF-I to patients with Laron-type dwarfism
      seems to have a beneficial effect on growth similar to that observed with long
      term administration of GH in children with GH deficiency.

PMID- 1349671
TI  - Parkinson's disease: one illness or many syndromes?

PMID- 1349670
TI  - Localised alveolar-septal amyloidosis with hypersensitivity pneumonitis.
AB  - Localised alveolar-septal amyloidosis has been thought irreversible. A woman
      exposed to the dust of sea-snail shells during the manufacture of nacre buttons
      had clinical and immunological features typical of hypersensitivity pneumonitis;
      however, transbronchial lung biopsy showed alveolar-septal amyloidosis. There was
      no evidence of other diseases known to be associated with amyloidosis, nor were
      amyloid deposits found in other organs. After a year without exposure to the
      antigen there was no trace of either pneumonitis or amyloidosis.

PMID- 1349672
TI  - Ascariasis: indiscriminate or selective mass chemotherapy?

PMID- 1349673
TI  - Pressure on the eco-seams.

PMID- 1349674
TI  - Tobacco's toll.

PMID- 1349675
TI  - Mortality from tobacco in developed countries: indirect estimation from national
      vital statistics.
AB  - Prolonged cigarette smoking causes even more deaths from other diseases than from
      lung cancer. In developed countries, the absolute age-sex-specific lung cancer
      rates can be used to indicate the approximate proportions due to tobacco of
      deaths not only from lung cancer itself but also, indirectly, from vascular
      disease and from various other categories of disease. Even in the absence of
      direct information on smoking histories, therefore, national mortality from
      tobacco can be estimated approximately just from the disease mortality statistics
      that are available from all major developed countries for about 1985 (and for
      1975 and so, by extrapolation, for 1995). The relation between the absolute
      excess of lung cancer and the proportional excess of other diseases can only be
      approximate, and so as not to overestimate the effects of tobacco it has been
      taken to be only half that suggested by a recent large prospective study of
      smoking and death among one million Americans. Application of such methods
      indicates that, in developed countries alone, annual deaths from smoking number
      about 0.9 million in 1965, 1.3 million in 1975, 1.7 million in 1985, and 2.1
      million in 1995 (and hence about 21 million in the decade 1990-99: 5-6 million
      European Community, 5-6 million USA, 5 million former USSR, 3 million Eastern and
      other Europe, and 2 million elsewhere, [ie, Australia, Canada, Japan, and New
      Zealand]). More than half these deaths will be at 35-69 years of age: during the
      1990s tobacco will in developed countries cause about 30% of all deaths at 35-69
      (making it the largest single cause of premature death) plus about 14% of all at
      older ages. Those killed at older ages are on average already almost 80 years
      old, however, and might have died soon anyway, but those killed by tobacco at 35
      69 lose an average of about 23 years of life. At present just under 20% of all
      deaths in developed countries are attributed to tobacco, but this percentage is
      still rising, suggesting that on current smoking patterns just over 20% of those
      now living in developed countries will eventually be killed by tobacco (ie, about
      a quarter of a billion, out of a current total population of just under one and a
      quarter billion).

PMID- 1349676
TI  - Randomised comparison of olsalazine and mesalazine in prevention of relapses in
      ulcerative colitis.
AB  - Sulphasalazine extends remissions and lessens disease activity during relapses of
      ulcerative colitis, but it also causes many adverse side-effects. The adverse
      reactions are mostly attributable to the sulphapyridine carrier moiety rather
      than the active principle 5-aminosalicylic acid (5-ASA), so agents to deliver 5
      ASA to the colon by other means have been designed. We have compared the efficacy
      and tolerability of two such agents, olsalazine and mesalazine, in maintenance
      therapy of ulcerative colitis. 100 patients with ulcerative colitis in remission
      were recruited at one centre and assigned randomly to treatment with olsalazine
      (Dipentum; 1.0 g daily) or mesalazine (Asacol, with Eudragit-S coating; 1.2 g
      daily). Compliance, biochemical and haematological variables, and clinical
      evidence of disease activity were assessed every 3 months for 12 months by
      observers unaware of treatment allocation. In intention-to-treat analysis, which
      included as treatment failures patients withdrawn for protocol violations,
      adverse reactions, intercurrent illness, or non-compliance as well as those with
      relapses of ulcerative colitis, the olsalazine group had a significantly lower
      rate of treatment failure than the mesalazine group (12/49 [24%] vs 23/50 [46%];
      p = 0.025). Analysis restricted to 64 patients still in remission at 1 year and
      18 with relapses also showed a significant difference in relapse rate (olsalazine
      5/42 [12%] vs mesalazine 13/40 [33%]; p = 0.024). Both drugs were well tolerated;
      only 9 patients reported substantial side-effects. Olsalazine was clearly
      superior to mesalazine in prevention of relapses in ulcerative colitis,
      especially in patients with left-sided disease.

PMID- 1349677
TI  - Validity of methods used to test airway responsiveness in children.
AB  - Methods to test airway responsiveness to inhaled agonists in children were
      originally developed for use in adults, and agonist dosage regimens do not
      adequately correct for the size of the child. Because small children receive a
      higher dose relative to their body size than do large children, the age-related
      decline in airway responsiveness reported in many recent studies might reflect
      failure to adequately size-correct test dosages rather than a genuine
      physiological event. Until the administered doses of inhaled agonists can be
      satisfactorily size-corrected, tests of airway responsiveness in children should
      be regarded as qualitative rather than quantitative.

PMID- 1349678
TI  - AIDS and the Murdoch press.

PMID- 1349679
TI  - WHO: World Health Assembly.

PMID- 1349680
TI  - Alternative view on AIDS.

PMID- 1349681
TI  - Antibiotic prophylaxis and infective endocarditis.

PMID- 1349682
TI  - Conservative treatment of mild/moderate cervical dyskaryosis.

PMID- 1349683
TI  - Conservative treatment of mild/moderate cervical dyskaryosis.

PMID- 1349684
TI  - Conservative treatment of mild/moderate cervical dyskaryosis.

PMID- 1349685
TI  - Oral contraceptives and papillomavirus persistence in normal cervix.

PMID- 1349686
TI  - Helicobacter pylori reinfection 4 years post-eradication.

PMID- 1349687
TI  - 2,8-Dihydroxyadenine urolithiasis.

PMID- 1349688
TI  - Fluoxetine side-effects mimicking hypoglycaemia.

PMID- 1349689
TI  - 2,8-Dihydroxyadenine urolithiasis.

PMID- 1349690
TI  - 2,8-Dihydroxyadenine urolithiasis.

PMID- 1349691
TI  - Rechallenge in clozapine-induced agranulocytosis.

PMID- 1349692
TI  - The narcolepsy susceptibility gene.

PMID- 1349693
TI  - H-RAS point mutations in leukaemias and lymphomas.

PMID- 1349694
TI  - Time to finish with "AIDS"?

PMID- 1349695
TI  - Impact of revision of AIDS case definition. Groupe d'Epidemiologie Clinique du
      SIDA en Aquitaine (GECSA)

PMID- 1349696
TI  - T-cell receptor variable gene products and early HIV-1 infection.

PMID- 1349697
TI  - Sex of children born to mothers with cystic fibrosis.

PMID- 1349698
TI  - Lamotrigine in primary generalised epilepsy.

PMID- 1349699
TI  - Frequency of inhibitors in haemophiliacs.

PMID- 1349700
TI  - Frequency of inhibitors in haemophiliacs.

PMID- 1349701
TI  - Casualties of election-year language.

PMID- 1349702
TI  - NHS trusts and Jehovah's Witnesses.

PMID- 1349703
TI  - Western donors and the former Soviet Union.

PMID- 1349704
TI  - Vitamin A and childhood morbidity.

PMID- 1349705
TI  - Effects of dioxins on thyroid function in newborn babies.

PMID- 1349706
TI  - Benzodiazepines and violent deaths.

PMID- 1349707
TI  - Pulmonary-renal syndrome in association with anti-GBM and IgM ANCA.

PMID- 1349708
TI  - Warm heart surgery.

PMID- 1349709
TI  - Warm heart surgery.

PMID- 1349710
TI  - Warm heart surgery.

PMID- 1349712
TI  - Uterine devices and pelvic inflammatory disease.

PMID- 1349711
TI  - Uterine devices and pelvic inflammatory disease.

PMID- 1349713
TI  - Inhibitory effects of beta-alanine on the vagal efferent and afferent excitatory
      responses of the stomach to stimulation of vagal trunk in cats.
AB  - The effects of beta-alanine on the electrically evoked vagal efferent
      (hexamethonium-sensitive initial excitatory response) and afferent (hexamethonium
      resistant delayed excitatory response) responses of the cat stomach were studied.
      beta-alanine (30 to 300 micrograms/kg, i.v.) dose-dependently inhibited both the
      efferent and afferent response. The IC50 values of beta-alanine on the efferent
      and afferent response were 296 +/- 65 micrograms/kg and 128 +/- 35 microgram/kg,
      respectively. Maximal inhibitory effects of beta-alanine (300 micrograms/kg,
      i.v.) appeared about 1 hr after the injection. Glycine and taurine (100 to 10,000
      micrograms/kg) did not affect these responses. Treatment with hexamethonium (10
      mg/kg, i.v.) prevented the efferent response, but augmented the afferent
      response. The treatment with hexamethonium abolished the inhibitory effect of
      beta-alanine on the afferent response. Both picrotoxin (100 and 500
      micrograms/kg, i.v.) and bicuculline (2000 micrograms/kg, i.v.) antagonized the
      inhibitory effects of beta-alanine on the vagal efferent and afferent responses
      of the stomach. The present experiments clearly demonstrated that beta-alanine
      inhibited both the vagal efferent and afferent excitatory responses of stomach to
      electrical stimulation of vagal trunk in cats.

PMID- 1349714
TI  - Antipunishment effects of acute and repeated administration of phencyclidine and
      NPC 12626 in rats.
AB  - The effects of phencyclidine (PCP) and NPC 12626 on punished responding were
      examined using a modified Geller-Seifter procedure in rats. Both drugs are known
      to antagonize N-methyl-D-aspartate (NMDA) receptor mediated neurotransmission,
      albeit at different sites on the NMDA receptor complex. Rats were trained to
      lever press for food reinforcement under a multiple schedule, with responding in
      one component reinforced under a fixed-interval 60-sec schedule, while each
      response in the other component resulted in both food and brief electric shock.
      Both PCP and NPC 12626 produced selective increases in punished responding,
      although the effects were not as large as those produced by chlordiazepoxide.
      Repeated daily administration of each of these drugs for 6 days resulted in
      increases in punished responding during different portions of the treatment. A 5
      mg/kg dose of chlordiazepoxide produced increases over the last 2 days of
      administration. PCP (2 mg/kg) produced an increase only during the second
      session, whereas NPC 12626 (30 mg/kg) produced increases for all but the first
      and fifth days of the 6-day regimen. Both competitive and noncompetitive NMDA
      antagonists can have antipunishment effects in this model.

PMID- 1349715
TI  - A low protein-high carbohydrate diet decreases D2 dopamine receptor density in
      rat brain.
AB  - The property of D2 dopamine receptors in the rat brain was evaluated after long
      term dietary manipulation. Groups of rats were pair-fed with equicaloric diet
      containing low protein (8%)-high carbohydrate, high protein (52%)-low
      carbohydrate and normal protein (20%) for 36 weeks. The low protein-high
      carbohydrate fed rats exhibited a significant decrease in the density (Bmax) of
      D2 dopamine receptor in the striatum (28%) and the mesolimbic regions (36%) with
      no apparent change in the receptor affinity (Kd). These findings suggest that
      long-term consumption of a low protein-high carbohydrate diet, by decreasing D2
      dopamine receptor density, may be an important determinant of central
      dopaminergic function.

PMID- 1349716
TI  - Esterification of fatty acids by bovine intramuscular and subcutaneous adipose
      tissues.
AB  - Exogenous fatty acid esterification in intramuscular and subcutaneous adipose
      tissues from 72-hr fasted or ad libitum fed Angus cattle was investigated.
      Intramuscular (interfascicular) and subcutaneous adipose tissue snips were
      obtained from the longissimus dorsi muscle and were incubated with
      radioisotopically labeled fatty acids (palmitate, stearate, oleate, linoleate or
      linolenate) at three different concentrations (0.3 mM, 0.6 mM and 2.0 mM) to
      assess rates of fatty acid incorporation into glycerolipids. Rates of fatty acid
      esterification in vitro increased with fatty acid concentration in both
      intramuscular and subcutaneous adipose tissues. For all of the fatty acids
      investigated, triglycerides were the predominant products (60-85%). Subcutaneous
      adipose tissue had larger adipocytes and more actively (P less than 0.05)
      esterified fatty acids, with the exception of palmitate, than intramuscular
      adipose tissue. The rate of palmitate esterification was not different between
      tissues, although intramuscular adipose tissue esterified a greater proportion (P
      less than 0.10) of palmitate as triglyceride (85%) than did subcutaneous adipose
      tissue (75%). Relative rates of incorporation of fatty acids into lipids in
      intramuscular and subcutaneous adipose tissues were: palmitate greater than
      linolenate greater than linoleate greater than stearate. In general, 72-hr
      fasting did not significantly reduce the rates of fatty acid incorporation in
      bovine adipose tissues. Results of this study revealed that:i) rates of exogenous
      fatty acid incorporation into adipose tissue lipids were dependent on the medium
      fatty acid concentration and adipose tissue depot; and ii) the relative
      esterification rates of the various fatty acids in vitro did not necessarily
      reflect the proportion of these fatty acids in bovine adipose tissues.

PMID- 1349717
TI  - Docosahexaenoic acid in developing brain and retina of piglets fed high or low
      alpha-linolenate formula with and without fish oil.
AB  - Docosahexaenoic acid (22:6n-3) can be synthesized in the liver and/or brain from
      alpha-linolenic acid (18:3n-3) and is required in large amounts in structural
      membranes of developing brain and retina. The adequacy and efficacy of formulas
      containing 18:3n-3 and/or fish oil in providing 22:6n-3 for deposition was
      investigated in piglets fed formula from birth to 15 days. The test formulas
      contained high (HL) or low (LL) 18:3n-3 (3.9 or 0.7% of the total formula fatty
      acids, respectively), or low 18:3n-3 plus fish oil (LL+FO) to provide C20 and C22
      n-3 polyunsaturated fatty acids (0.8% of total fatty acids). Fatty acid analyses
      of synaptic plasma membrane and retina ethanolamine phospholipids (EPL), which
      are especially enriched in 22:6n-3, were compared to those of 15-day-old piglets
      fed sow milk (SM). Feeding LL resulted in lower 22:6n-3 in synaptic plasma
      membrane. Fatty acid levels in HL and LL+FO piglets were equivalent to SM, with
      the exception of lower 22:5n-3 in the synaptic plasma membrane of LL+FO and in
      the retina of HL and LL+FO-fed piglets. Levels of 22:4n-6 were also lower in the
      retina of the LL+FO group. The results suggest formula 18:3n-3 is at least 24% as
      effective as C20 and C22 n-3 fatty acids as a source of membrane 22:6n-3. This
      study shows dietary 18:3n-3, as the only n-3 fatty acid, can support deposition
      of comparable percentage of 22:6n-3 to natural milk. Fish oil also supported
      tissue levels of 22:6n-3 similar to natural milk; however, lower 22:4n-6 may
      indicate possible inhibitory effects on n-6 metabolism.

PMID- 1349719
TI  - Chronic stress elevates enkephalin expression in the rat paraventricular and
      supraoptic nuclei.
AB  - Numerous studies have implicated opioids in the regulation of hypothalamic
      functions. Dynorphin, which is co-expressed with vasopressin in the magnocellular
      neurons of the paraventricular and supraoptic nuclei, is co-regulated with
      vasopressin in response to hyperosmolality and appears to inhibit vasopressin and
      oxytocin release from the posterior pituitary. Enkephalin is present in
      paraventricular parvocellular neurons and its expression is elevated in response
      to various stresses. However, enkephalin's presence and roles in paraventricular
      and supraoptic magnocellular neurons are uncertain. By giving rats daily
      intraperitoneal injections of hypertonic saline for up to 12 days, we induced a
      marked increase in enkephalin expression in magnocellular neurons of the
      paraventricular and supraoptic nuclei, beyond what develops from drinking
      hypertonic saline. Our results suggest that enkephalin expression in both
      vasopressin and oxytocin neurons may increase in response to chronic stresses and
      provide another source of enkephalin in addition to the parvocellular neurons.

PMID- 1349718
TI  - BMY 14802, a potential antipsychotic drug, increases expression of proneurotensin
      mRNA in the rat striatum.
AB  - Treatment with efficacious antipsychotic drugs, such as haloperidol, increases
      the concentrations of neurotensin (NT) in the nucleus accumbens and caudate
      nucleus of the rat. The increases in NT content produced by haloperidol have been
      shown to be associated with an increase in NT biosynthesis as assessed by the
      level of expression of proNT mRNA. The potential antipsychotic drug and sigma
      receptor ligand BMY 14802 has been shown to produce increases in the
      concentrations of NT in the nucleus accumbens and caudate that are similar to
      those produced by haloperidol with respect to the magnitude of the increases and
      the time course over which they occur. This study evaluated the effects of BMY
      14802 on the expression of proNT mRNA and NT concentration in the rat striatum.
      Three hours after a single injection of BMY 14802 (35 mg/kg, i.p.) expression of
      proNT mRNA was significantly increased in the nucleus accumbens and caudate.
      Labeling was most intense in the dorsal caudate. NT concentrations were unaltered
      at this time point. Eighteen hours after injection, significant increases in NT
      concentration in the nucleus accumbens and caudate were detected. At this time,
      expression of proNT mRNA was substantially reduced compared to 3 h after
      treatment although labeling of the dorsal and medial caudate was still greater
      than that observed in controls.

PMID- 1349720
TI  - Induction of immediate-early gene proteins in dentate granule cells and
      somatostatin interneurons after hippocampal seizures.
AB  - The expression of the protein products of the immediate-early genes c-fos, Fos B,
      Fos-related proteins (FRAs), c-jun, jun B, jun D and krox-24 was investigated in
      the rat hippocampus at various times after electrically-induced hippocampal
      seizures. Hippocampal seizures induced all the immediate-early gene proteins in
      dentate granule cells with differing time-courses. In addition, Krox-24, Fos and
      Jun D were also induced in somatostatin-containing interneurons throughout the
      hippocampus and also in a small percentage of parvalbumin-containing
      interneurons. Thus, hippocampal seizures induce waves of immediate-early gene
      protein expression in dentate granule cells and a selective expression of krox
      24, Fos and Jun D in hippocampal somatostatin interneurons. These results suggest
      that biochemical and/or morphological changes occurring in dentate granule cells
      and somatostatin interneurons after seizures may be regulated by immediate-early
      gene expression, and that these immediate-early gene proteins may be involved in
      seizure development in the nervous system.

PMID- 1349721
TI  - A dementing illness associated with a novel insertion in the prion protein gene.
AB  - Following our previous report of an 144-bp insertion in the open reading frame of
      the prion protein (PrP) gene, we have now identified a larger, 216-bp, insertion
      in the gene. The insertion which is in frame encodes 9 extra octapeptide repeat
      sequences in addition to the 5 repeats normally present and represents the
      largest insertion so far detected in the PrP gene.

PMID- 1349723
TI  - European Environmental Mutagen Society. 13th meeting. Heidelberg, FRG, September
      25-27, 1991. Abstracts.

PMID- 1349722
TI  - Temporal changes in tyrosine hydroxylase mRNA levels in A1, A2 and locus ceruleus
      neurons following electrical stimulation of A1 noradrenergic neurons.
AB  - We examined the effects of electrical stimulation (ES) of right A1 noradrenergic
      cells on temporal changes in tyrosine hydroxylase (TH) mRNA levels in A1, A2 and
      locus ceruleus (LC) neurons by in situ hybridization histochemistry and
      quantitative image analysis methods. The stimulation parameters used previously
      have been shown to increase hypothalamic norepinephrine (NE) release. Within 1 h
      after beginning A1 stimulation, TH mRNA levels were significantly increased and
      they continued to rise to reach plateau by 6 h. TH message levels at 12 h were
      not difference from 6 h values. A1-ES did not affect TH mRNA levels in
      contralateral A1 or in A2 or locus ceruleus neurons. These data suggest that
      changes in TH mRNA levels may serve as an index of increased A1 neuronal activity
      in circumstances when increases in hypothalamic NE secretion occur.

PMID- 1349725
TI  - [Takayasu aortic arteritis].

PMID- 1349726
TI  - [Current strategies in the treatment of tumor pain].

PMID- 1349724
TI  - Immunobiology of experimental leishmaniasis.
AB  - Self-cure versus uncontrolled disease progression in experimental murine
      cutaneous leishmaniasis depends upon a delicate interplay among various activated
      cells of the host's immune system. Susceptibility or resistance to infection with
      Leishmania major is correlated with the ability of different inbred strains of
      mice to produce the characteristic spectra of lymphokines upon infection.
      Appropriate experimental interventions now allow the modulation of these
      responses, providing the possibility to render genetically susceptible mice
      resistant to infection and, vice versa, to cause genotypically "healer" strains
      to express a "non-healer" phenotype. These experimental manipulations have proven
      to be powerful tools in the dissection of the underlying immune mechanisms and
      cellular parameters responsible for susceptibility and resistance, and will
      perhaps allow the identification of molecules of parasite origin that induce
      deleterious immune responses to infection with Leishmania, and thus to exclude
      them from future vaccines. More importantly, rational immune intervention could
      permit the diversion of established host-damaging immune responses to host
      protective immunization.

PMID- 1349728
TI  - Glutamate-induced long-term potentiation of the frequency of miniature synaptic
      currents in cultured hippocampal neurons.
AB  - Glutamate application at synapses between hippocampal neurons in culture produces
      long-term potentiation of the frequency of spontaneous miniature synaptic
      currents, together with long-term potentiation of evoked synaptic currents. The
      mini frequency potentiation is initiated postsynaptically and requires activity
      of NMDA receptors. Although the frequency of unitary quantal responses increases
      strongly, their amplitude remains little changed with potentiation. Tests of
      postsynaptic responsiveness rule out recruitment of latent glutamate receptor
      clusters. Thus, postsynaptic induction can lead to enhancement of presynaptic
      transmitter release. The sustained potentiation of mini frequency is expressed
      even in the absence of Ca2+ entry into presynaptic terminals.

PMID- 1349729
TI  - Heat shock in Escherichia coli alters the protein-binding properties of the
      chaperonin groEL by inducing its phosphorylation.
AB  - When bacterial or eukaryotic cells are exposed to high temperatures or other
      harsh conditions, they respond by synthesis of a specific set of heat-shock
      proteins. Certain heat-shock proteins such as groEL, called 'chaperonins', can
      prevent misfolding and promote the refolding and proper assembly of unfolded
      polypeptides generated under harmful conditions. We report here a new aspect of
      the heat-shock response in Escherichia coli: at high temperatures a fraction of
      groEL becomes modified covalently, altering its interaction with unfolded
      proteins. The heat-modified form can be eluted with ATP from an unfolded protein
      more easily than normal groEL. The critical heat-induced modification seems to be
      phosphorylation, which is reversed on return to low temperature. Treatment of the
      modified groEL with phosphatases caused its apparent size, charge and binding
      properties to resemble those of the unmodified form. Thus during heat shock some
      groEL is reversibly phosphorylated, which allows its ATP-dependent release from
      protein substrates in the absence of its usual cofactor (groES), and probably
      promotes the repair of damaged polypeptides.

PMID- 1349727
TI  - Optimal drug and behavior therapy for treatment-refractory institutionalized
      schizophrenics.
AB  - Institutionalized persons with a deteriorating form of schizophrenia that was
      refractory to neuroleptic medication were titrated downward in their haloperidol
      dose. Based on ratings of their clinical status, an optimal dose was reached that
      was an average 66 percent reduction from their initial levels. Patients then
      participated in a personalized, intensive behavior therapy program to remediate
      their extreme, persisting deficits and disturbances in behavior.

PMID- 1349730
TI  - Somatostatin and neuropeptide Y in organotypic slice cultures of the rat
      hippocampus: an immunocytochemical and in situ hybridization study.
AB  - The neuronal distributions of somatostatin and neuropeptide Y and their
      respective mRNAs in hippocampal slice cultures were examined by
      immunohistochemical staining and in situ hybridization. For the in situ
      hybridization we used an alkaline phosphatase-labelled oligodeoxynucleotide probe
      for somatostatin mRNA and an 35S-labelled oligodeoxynucleotide probe for
      neuropeptide Y mRNA. For both neuropeptides the immunostained and hybridized
      neurons displayed a comparable, organotypic distribution. Most labelled neurons
      were located in the dentate hilus and stratum oriens of CA3 and CA1. Additional
      neurons were found in stratum radiatum and pyramidale of CA3, but very few in the
      corresponding layers of CA1. In all locations the density of somatostatin- and
      neuropeptide Y-reactive cells exceeded that observed in vivo. Also, the
      hybridization signal of the individual neurons appeared enhanced in the slice
      cultures. Methodologically it was noted that the non-radioactive alkaline
      phosphatase-labelled oligodeoxynucleotide probe gave excellent in situ
      hybridization results with detailed cellular resolution and no apparent problems
      of tissue penetration, even when used on whole-mount explants. These results
      demonstrate that somatostatin and neuropeptide Y-immunoreactive and mRNA
      containing neurons retain their organotypic distribution and basic morphological
      characteristics in the slice cultures. The supernormal density of these neurons
      and their hybridization signals indicate that a transient developmental increase
      in neuropeptide expression may persist in vitro.

PMID- 1349731
TI  - Distribution of somatostatin immunoreactivity in the forebrain of the squirrel
      monkey: basal ganglia and amygdala.
AB  - The distribution of somatostatin immunoreactivity in the basal ganglia and
      amygdala of the squirrel monkey (Saimiri sciureus) was studied with specific
      polyclonal antibodies directed against somatostatin-28 and somatostatin-28(1-12).
      Both antibodies gave similar results with regard to the distribution of
      somatostatin-immunoreactive neuronal profiles. A moderately dense and highly
      heterogeneous network of somatostatin-positive fibers was observed throughout the
      striatum. A dorsoventral gradient of increasing immunoreactivity was noted in the
      striatum and the caudate nucleus was found to strain generally less intensely
      than the putamen. The immunoreactive fibers within the striatum were mostly thin
      and varicose and formed patches corresponding to the striosomes, as visualized on
      adjacent sections immunostained for calbindin. Although some somatostatin cell
      bodies rimmed the striosomes, most of the positive cells were rather uniformly
      scattered in the striatum. These medium-sized cells were significantly smaller in
      the caudate nucleus (93 microns2, S.D. = 26 microns2) than in the putamen (122
      microns2, S.D. = 39 microns2), but their density was significantly higher in the
      caudate nucleus (29.7 cells/mm2, S.D. = 8.8 cells/mm2) than in the putamen (20.5
      cells/mm2, S.D. = 7.0 cells/mm2). The nucleus accumbens stained moderately and
      positive cell bodies were evenly dispersed throughout this structure. In
      contrast, the olfactory tubercle displayed a heavily stained neuropil but
      positive neurons were encountered only in its polymorph layer. In the
      sublenticular region, dense fiber plexuses appeared in register with nonreactive
      cell clusters of the nucleus basalis of Meynert and of the nucleus of the
      anterior commissure. More caudally, a dense bundle of positive fibers was
      observed at the level of the ansa lenticularis, the inferior thalamic peduncle,
      and the adjoining bed nucleus of the stria terminalis. Several fibers
      contributing to this bundle were of the woolly type. Woolly fibers also coursed
      in the substantia innominata between the ventral aspect of the globus pallidus
      and the optic tract, and ascended in the internal medullary lamina separating the
      internal and external segments of the globus pallidus. Somatostatin
      immunoreactive cell bodies were uniformly scattered throughout the substantia
      innominata. The various nuclei of the amygdala showed a wide range of
      immunoreactivity. The central nucleus was lightly reactive, whereas the
      intercalated masses displayed a moderate staining. A dorsoventral gradient of
      immunostaining was noted in the ventrolateral portion of the amygdala, the
      lateral nucleus being moderately to densely stained and the basal nucleus very
      lightly to lightly immunoreactive.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1349732
TI  - Blockade of hippocampal long-term potentiation by saccharin.
AB  - Population spikes, population excitatory postsynaptic potentials and
      intracellular excitatory postsynaptic potentials were recorded in the CA1 area of
      guinea-pig hippocampal slices in response to low frequency stimulation of the
      stratum radiatum. Tetanic stimulation of the same afferents during an application
      of saccharin (10 mM, 10 min) failed to induced a long-term potentiation of the
      population spike, population excitatory postsynaptic potential and
      intracellularly recorded excitatory postsynaptic potential. A post-tetanic
      application of saccharin did not prevent long-term potentiation of the population
      spike from developing. Saccharin did not change the input resistance, the
      membrane potential or the ability to induce action potentials in the CA1 neurons.
      The slope of the intracellular excitatory postsynaptic potentials recorded in
      normal medium, in normal medium containing 2-amino-5-phosphonovalerate, or in
      Mg(2+)-free medium containing 6-cyano-7-nitroquinoxaline-2,3-dione was not
      significantly altered by saccharin. The depolarizations of CAI neurons produced
      by superfusion of N-methyl-D-aspartate or during a brief tetanic stimulation of
      the stratum radiation were also not altered by the drug. It therefore appears
      that saccharin blocks the induction of long-term potentiation by a mechanism that
      does not involve a blockade of N-methyl-D-aspartate receptors. Application of
      fluid samples collected from rabbit neocortical surface during a tetanic
      stimulation of the neocortex caused neurite growth in PC-12 cells, suggesting
      that growth-related substances were present in the collected samples. If these
      samples were superfused onto hippocampal slices, long-term potentiation
      developed. If however, the samples were co-applied with saccharin, neither
      neurite growth in PC-12 cells nor long-term potentiation in hippocampal slices
      was observed, raising the possibility that growth-related substances are involved
      in long-term potentiation.

PMID- 1349733
TI  - Contribution of an alpha 1-adrenergic receptor subtype to the expression of the
      "ventral tegmental area syndrome".
AB  - Bilateral electrolytic lesions of the rat ventral tegmental area, a mesencephalic
      structure containing the cell bodies of ascending dopaminergic neurons, induce a
      behavioural syndrome characterized by a permanent locomotor hyperactivity. Acute
      intraperitoneal injections of prazosin, an alpha 1-adrenergic receptor
      antagonist, at a dose (0.5 mg/kg) which does not affect locomotor activities of
      control animals, abolished locomotor hyperactivities of lesioned rats.
      Antagonists of other monoaminergic receptors (propranolol, ritanserin,
      yohimbine), and also another antagonist of alpha 1-adrenergic receptors, 2-(2',6'
      dimenthoxyphenoxyethyl)-aminomethyl-1,4-benzodioxan (WB4101) were ineffective.
      Comparisons of autoradiograms of brain slices incubated in the presence of 1 nM
      [3H]prazosin or 10 nM [3H]WB4101 indicated clear topographical differences.
      [3H]Prazosin labelling is present in the septum and in layer III of the cerebral
      cortex but absent in the striatum. [3H]WB 4101 labelling is diffuse in the
      superficial layers of the cerebral cortex and present in the striatum. In
      addition, intraperitoneal injection of WB4101 displaces, only weakly,
      [3H]prazosin binding in layer III of the cerebral cortex (-18%) while it
      decreases by 50% [3H]prazosin binding in the more superficial cortical layers.
      These observations strongly suggest that the binding site labelled by
      [3H]prazosin is different from alpha 1A- and alpha 1B-adrenergic receptor
      subtypes labelled by [3H]WB4101. Finally, it is proposed that the prazosin
      induced blockade of the locomotor hyperactivity exhibited by ventral tegmental
      area lesioned animals is linked to the previously demonstrated regulatory role of
      noradrenergic neurons on cortical dopamine transmission.

PMID- 1349734
TI  - Early and widespread normalization of dopamine-neuropeptide Y interactions in the
      rat striatum after transplantation of fetal mesencephalon cells.
AB  - Graft-to-host interactions were examined at cellular level, by measuring changes
      in the immunoreactivity of striatal interneurons expressing neuropeptide Y after
      dopamine denervation and transplantation of fetal mesencephalon neurons into the
      striatum of adult rats. Mesencephalic cell suspensions were implanted
      unilaterally into the dorsal part of the striatum in rats two weeks after
      intranigral injection of 6-hydroxydopamine. One month and three to four months
      later, rats showing abolition of amphetamine-induced turning were perfused.
      Serial brain sections containing intrastriatal grafts were treated for tyrosine
      hydroxylase and neuropeptide Y immunocytochemistry, and neuropeptide Y
      immunoreactive neurons were quantified in various parts of the striatal surface
      and compared with the striatum of controls and age-matched rats with lesions.
      Biochemical analyses of dopamine and dihydroxyphenyl acetic acid tissue levels
      and [3H]dopamine uptake were also performed on striatal samples from similar
      groups of normal, lesioned and transplanted rats. As early as one month post
      grafting, a complete reversal of the increase in the number of neuropeptide Y
      immunoreactive neurons occurring after 6-hydroxydopamine lesion was observed in
      dopamine-grafted animals, although a partial restoration of the tyrosine
      hydroxylase immunostaining and a recovery of 8% dopamine tissue level were
      observed in the striata of grafted as compared to normal rats. This effect on the
      host immunoreactivity was found to be specific to dopamine grafts, since no
      reversal was observed in sham-spinal cord-transplanted rats. Moreover, similar
      degrees of normalization were recorded either in the total striatum, or in the
      area immediately adjacent to the graft, or even in the zone most sensitive to
      dopamine denervation in terms of neuropeptide Y immunoreactivity. No more
      pronounced functional effects were observed three to four months after
      transplantation. These data suggest that grafted dopamine neurons are able to
      induce rapid and extensive host responsiveness, possibly by means of mechanisms
      involving synaptic and diffuse release of dopamine and adaptive changes in the
      host brain. These data may provide a cellular basis for interpreting larger
      behavioural recoveries than those expected to occur with dopamine grafts in view
      of the partial restoration of the dopaminergic innervation.

PMID- 1349735
TI  - Mechanisms of glutamate activation of axon-to-Schwann cell signaling in the
      squid.
AB  - Membrane potentials from Schwann cells associated with giant axons of the small
      squid (Alloteuthis and Loliguncula) and the large squid (Loligo) were monitored
      with glass microelectrodes following 100 Hz/15 s axonal stimulation, or the
      application of 10(-7) M glutamate and ion substitutions, in the presence or
      absence of 10(-7) M d-tubocurarine. Glutamate or stimulation caused the membrane
      of the Schwann cell to depolarize to approximately -32 mV. This was rapidly
      replaced by a transient hyperpolarization to approximately -55 mV; the potential
      returning to the resting level (-40 mV) in approximately 7 min. In the presence
      of d-tubocurarine only the initial depolarization was evident. Nominally zero
      [Na+]o or treatment with 10(-7) M tetrodotoxin (in normal [Na+]o) blocked the
      stimulation- and glutamate-induced depolarization while low Clo- hyperpolarized
      the Schwann cell without effect on the glutamate- or stimulation-induced
      depolarization. Nao+ depletion or pretreatment with tetrodotoxin in normal Nao+
      did not affect the development of the Schwann cell hyperpolarization. These
      results do not support the hypothesis that the glutamate-induced depolarization
      is the trigger leading to the Schwann cell hyperpolarization. Preliminary
      experiments to test the possibility that inositol phosphate second messenger and
      an increase in [Ca2+]i are triggered by glutamate receptor activation showed that
      nominally 0 Cao2+/75 mM Mgo2+ only slightly reduced the hyperpolarizing response
      to stimulation or glutamate while intracellular Bapta (20-30 microM) blocked the
      hyperpolarization but not the depolarization. [3H]Myoinositol incorporation into
      axon-Schwann cell plasma membranes was high.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349736
TI  - Neuroprotective effects of graded reoxygenation following chronic hypoxia in
      neuronal cell cultures.
AB  - The present study was undertaken to investigate the comparative effects of rapid
      vs graded correction of chronic hypoxia in vitro. Cerebral cortical cell cultures
      obtained from fetal mice were exposed to 5% O2 for 24 h and returned immediately
      to room air for the following 24 h (Group I); comparable cultures were exposed to
      5% O2 for 24 h followed by 10% O2 for an additional 24 h before return to room
      air (Group II). At the conclusion of the experimental protocol (time 0), partial
      pressure of oxygen in the bathing medium of Group I cultures was significantly
      higher than that of Group II and non-hypoxic controls (151 mmHg vs 124 and 132
      mmHg, respectively; P less than 0.05). Throughout the recovery period, Group II
      cultures evidenced improved neuronal survival (e.g. 35,800 vs 17,700
      neurons/culture well at time 0, P less than 0.01), decreased lactate
      dehydrogenase efflux into the bathing medium, relative preservation of neuronal
      morphology, as well as higher specific and clonazepam-displaceable benzodiazepine
      binding and GABA uptake. Glutamate binding was not differentially affected and
      glutamine synthetase activity, a predominantly glial marker, was only modestly
      increased after graded reoxygenation. These results demonstrate that gradual
      reoxygenation after prolonged hypoxia in vitro (i) improves neuronal survival
      compared to rapid reoxygenation and (ii) delays the manifestations of metabolic
      dysfunction even though the length of hypoxic exposure is increased. The findings
      are also consistent with the concept that a period of relative hyperoxia may
      contribute to hypoxia-induced neuronal injury.

PMID- 1349738
TI  - 36th annual meeting of the Royal College of Pathologists of Australasia.
      Melbourne, Victoria, 30 September-4 October 1991. Abstracts.

PMID- 1349737
TI  - Tyrosine hydroxylase and neuropeptide Y are increased in ciliary ganglia of
      sympathectomized rats.
AB  - We have examined the expression of tyrosine hydroxylase and neuropeptide Y in
      ciliary ganglia of normal adult rats and of adult rats in which the environment
      of these neurons was altered by sympathectomy at birth. Following neonatal 6
      hydroxydopamine treatment, the proportion of tyrosine hydroxylase-immunoreactive
      and neuropeptide Y-immunoreactive neurons in ciliary ganglia was significantly
      increased. In ciliary neurons of both control and sympathectomized rats,
      neuropeptide Y immunoreactivity was preferentially co-localized with tyrosine
      hydroxylase. Immunoblot analysis confirmed the presence of tyrosine hydroxylase
      and its increase following sympathectomy. In situ hybridization studies revealed
      that many ciliary neurons contain mRNA for tyrosine hydroxylase and for
      neuropeptide Y. Like tyrosine hydroxylase immunoreactivity, the number of ciliary
      neurons containing tyrosine hydroxylase mRNA and the amount of mRNA per cell were
      increased in 6-hydroxydopamine-treated rats. In contrast, neuropeptide Y mRNA
      levels were the same in control and 6-hydroxydopamine-treated rats. Nerve growth
      factor is a candidate for mediating the effects of sympathectomy and most ciliary
      neurons in control and sympathectomized rats expressed immunoreactivity for the
      low-affinity nerve growth factor receptor. In addition, ciliary neurons from 6
      hydroxydopamine-treated animals possessed increased nerve growth factor receptor
      immunoreactivity. These studies indicate that both tyrosine hydroxylase and
      neuropeptide Y in the ciliary ganglion are regulated by alterations in their
      environment. Their expression was enhanced by chemical sympathectomy which does
      not affect ciliary neurons directly but, rather, removes sympathetic innervation
      of shared targets, including the iris. In situ hybridization analysis suggests
      that the increased tyrosine hydroxylase and neuropeptide Y levels result from
      different mechanisms and provides evidence that neuropeptide levels can be
      regulated without changes in mRNA levels.

PMID- 1349739
TI  - Detection of beta and delta globin gene mutations by PCR and direct DNA
      sequencing in an individual with normal HbA2 beta thalassemia.
AB  - Normal HbA2 beta thalassemia in a Greek individual was shown to be due to co
      inheritance of beta and delta thalassemias. The genetic defects were
      characterized by enzymatic amplification of the beta and delta globin genes and
      direct genomic sequencing. Two children with a typical high HbA2 beta thalassemia
      trait had inherited the beta thalassemia allele whilst a third child had low
      normal HbA2 associated with delta+ thalassemia. Segregation patterns confirmed
      that the delta+/beta zero thalassemia defects were present in trans.

PMID- 1349740
TI  - Plasmid replication in Xenopus eggs and egg extracts: a 2D gel electrophoretic
      analysis.
AB  - We have examined the replication patterns of ribosomal DNA plasmids in vivo and
      in vitro using Xenopus eggs. Plasmids carrying different parts of the Xenopus
      ribosomal DNA sequence were allowed to replicate either in vitro in an egg
      extract or in vivo after microinjection into unfertilized eggs. The replication
      intermediates were analyzed by the 2D gel electrophoretic technique of Brewer and
      Fangman (1), using original or modified electrophoresis conditions. With standard
      electrophoresis conditions, the patterns obtained for restriction fragments
      larger than 5 kb were unreliable because of artefactually distorted Y arcs and
      unrecognizable bubble arcs. Interpretable patterns could nevertheless be obtained
      using suitably modified electrophoresis parameters. Under these conditions,
      replication was found to initiate and terminate at multiple, random locations on
      each plasmid both in vivo and in vitro. However, only one or very few of these
      potential initiation sites are used during the replication of an individual
      plasmid molecule. We discuss the possible artefacts and misinterpretations that
      can result when the 2D electrophoresis parameters are not adapted to the size of
      the fragment examined. We also discuss the relevance of the random replication
      mode to the mechanisms and the control of DNA replication in eukaryotes.

PMID- 1349741
TI  - A physical and genetic map of the Spiroplasma citri genome.
AB  - A physical and genetic map of the Spiroplasma citri genome has been constructed
      using several restriction enzymes and pulsed field gel electrophoresis. A number
      of genes were subsequently localized on the map by the use of appropriate probes.
      The genome size of the spiroplasma estimated from restriction fragments is close
      to 1780 kbp, the largest of all Mollicutes studied so far. It contains multisite
      insertions of Spiroplasma virus 1 (SpV1) sequences. The physical and genetic map
      of the S. citri genome shares several features with that of other Mollicutes,
      especially those in the Mycoplasma mycoides cluster. This supports the finding
      that S. citri and these Mycoplasma spp. are phylogenetically related.

PMID- 1349742
TI  - The murine Hox-2.4 promoter contains a functional octamer motif.
AB  - Like other HOX genes the murine Hox-2.4 gene is thought to be involved in
      regional specification along the antero-posterior axis. In addition it has been
      reported to have oncogenic potential. We studied expression Hox-2.4 in murine EC
      cells and determined the transcription start site. Studies of DNA-protein
      interactions in the promoter region showed that the Hox-2.4 promoter contains a
      CCAAT box and a perfect octamer motif, which is capable of binding Oct-factors.
      Cotransfection of Oct expression vectors influences the transcriptional activity
      of the promoter, suggesting that the Oct-gene family may be involved in
      regulating HOX genes.

PMID- 1349744
TI  - Antihypertensive therapy. Current issues and challenges.
AB  - Choosing antihypertensive agents that protect patients against cardiovascular and
      other complications is a growing trend in the treatment of mild to moderate
      hypertension. Calcium channel blockers and angiotensin-converting enzyme (ACE)
      inhibitors are favored because they have neutral or positive effects on lipid
      levels and insulin resistance. The alpha 1 blockers, especially doxazosin
      mesylate (Cardura), are enjoying a resurgence in popularity because they have a
      beneficial effect on lipid levels. In terms of preserving patients' quality of
      life, the ACE inhibitors in particular have been shown to have a positive impact.
      It has been shown that systolic hypertension in elderly patients should
      definitely be treated, but the most appropriate agent has yet to be defined.
      Therapy should be tailored to the individual. The following questions should be
      considered when choosing an antihypertensive agent: (1) What are its side effects
      (especially metabolic ones)? (2) Does it require only once- or twice-a-day
      dosing? (3) Does it cause regression of left ventricular hypertrophy? (4) Does it
      prevent death from coronary artery disease? (5) How will it affect quality of
      life? (6) How much does it cost? The goal of therapy should be to provide
      adequate blood pressure control throughout the day, enhance compliance, and
      protect the heart, brain, and kidneys without adversely affecting metabolic
      state.

PMID- 1349743
TI  - A conserved region in intron 1 negatively regulates the expression of the PCNA
      gene.
AB  - The Proliferating Cell Nuclear Antigen (PCNA) gene is a growth-regulated gene,
      whose expression is under the control of both transcriptional and
      posttranscriptional mechanisms. In previous work, it was shown that the 73 bp
      immediately upstream of the CAP site and intron 4 are major regulatory elements.
      We show here that intron 1 also plays a role in determining the levels of PCNA
      mRNA. Specifically, we show: 1) deletion of intron 1 increases the expression of
      PCNA mRNA in serum-deprived cells; 2) a 35 bp sequence in intron 1, containing a
      reverse CCAAT element specifically binds proteins from nuclear extracts; 3) this
      intron 1 sequence inhibits the expression of a co-tranfected human PCNA gene in
      transient expression assays suggesting that it competes for positive
      transcription factors; 4) mutations in the CCAAT region of the 35bp intron 1
      probe abrogate both its protein-binding capacity and its ability to inhibit the
      expression of a co-transfected wt PCNA gene; and 5) the CCAAT region of human
      intron 1 is highly conserved in the mouse gene. We conclude that the reverse
      CCAAT region of intron 1 is a negative regulatory element of PCNA gene
      expression, and hypothesize that its inhibitory effect is abolished when certain
      protein(s) bind to it and that inhibition is restored if these proteins are
      competed out by an homologous sequence.

PMID- 1349745
TI  - Supraventricular tachyarrhythmias in the intensive care unit.
AB  - Several types of supraventricular tachyarrhythmias occur commonly during
      intensive care. The specific type can usually be diagnosed using standard
      electrocardiographic techniques. Several new drugs have significantly improved
      the ability to successfully manage these arrhythmias.

PMID- 1349746
TI  - Anxiolytic potential of 5-HT3 receptor antagonists.
AB  - The 5-HT3 receptor antagonists such as ondansetron have been shown to have
      anxiolytic-like activity in a wide range of preclinical tests: in the mouse
      black: white test, the rat social interaction test, the rat elevated X-maze and
      the marmoset human threat test. Ondansetron, like other 5-HT3 receptor
      antagonists appears to have important advantages over existing anxiolytic
      therapies. Thus, the 5-HT3 receptor antagonists are not sedative, they do not
      have addictive liabilities, there are no problems of withdrawing from chronic
      treatment and they can be used following benzodiazepine withdrawal. Such
      compounds even inhibit the behavioural syndrome associated with withdrawal from
      drugs of abuse, nicotine, alcohol, cocaine, opiates. The preclinical data,
      therefore, indicates the 5-HT3 receptor antagonists as novel anxiolytics of the
      future, and there is new clinical work in support of this suggestion.

PMID- 1349747
TI  - The role of Mg2+ on the formation of the ternary complex between agonist, beta
      adrenoceptor, and GS-protein and an interpretation of high and low affinity
      binding of beta-adrenoceptor agonists.
AB  - In the absence of GTP or its analogues, the beta-adrenoceptor agonist (H), the
      receptor (R) and the stimulatory guanine nucleotide-binding regulatory protein
      (GS-protein) form a slowly dissociable complex (HRGSGDP). It is presumed that the
      agonist in this ternary complex is bound to the receptor with high affinity while
      its binding to the receptor in the HR-complex is of low affinity. We have studied
      the effect of Mg2+ on the formation of these two complexes by the displacement of
      (-)-[3H]CGP-12177 with (-)-isoprenaline in cell membranes prepared from guinea
      pig lung parenchyma. In the absence of Mg2+, only monophasic displacement curves
      were obtained with a dissociation constant not differing from that obtained in
      the presence of Gpp(NH)p and Mg2+. In the presence of Mg2+ and absence of
      Gpp(NH)p, a shallow binding curve was obtained that fitted a two site model best.
      One of the dissociation constants agreed well with that obtained in the presence
      of Gpp(NH)p and Mg2+ but the other one was 27 times smaller. It was concluded
      that Mg2+ is necessary for the coupling between the HR-complex and the GS
      protein. The two dissociation constants obtained in the absence of Gpp(NH)p
      represent the dissociation constants of the HR- and HRGSGDP-complexes and may
      correspond to those named KL and KH in the literature. According to our study,
      there may be no difference in affinity between the agonist and receptor in the HR
      and HRGSGDP-complexes. The two dissociation constants obtained in the absence of
      GTP or its analogues refer to two consecutive reactions.

PMID- 1349748
TI  - Evidence that drug binding to non-adrenergic [3H]-idazoxan binding sites (I
      receptors) occurs to interacting or interconvertible affinity forms of the
      receptor.
AB  - Characterization of [3H]idazoxan binding to guinea pig kidney membranes showed
      that approximately 90% bound to nonadrenergic I-receptors and approximately 10%
      to alpha 2-adrenoceptors. I-Receptors could be studied separately by including 3
      microM rauwolscine to the assay. During these conditions 22 different compounds
      out of 29 (including imidazoline and guanidinium compounds) generated biphasic or
      shallow competion curves (Hill coefficients down to 0.57), for which computer
      modelling suggested that drugs bound to two sites with different affinities.
      However, the proportion of sites varied considerably depending on which drug was
      used as competitor; the variation being from approximately 50/50% to
      approximately 8/92% and analysis of variance clearly indicated that the variation
      of proportions of sites could be attributed to an effect induced by the drugs
      which indicated that the sites were dynamically formed or modulated by the
      presence of the drug. A few drugs (guanabenz, (-)-medetomidine, phentolamine,
      clemastin, prazosin and idazoxan itself) yielded steep uniphasic curves (Hill
      coefficients near unity) which were resolved only into one site fits. One drug
      (detomidine) yielded supersteep competition curves (Hill coefficient 1.29), the
      data being reminiscent of positive cooperativity. In another set of experiments
      attempts were made to block one of the affinity forms of the I-receptor with
      histamine, a compound which had grossly different affinities for the two I
      receptor sites, and competition curves were then obtained using other drugs which
      also seemed to distinguish between the two sites. Computer analysis of
      experimentally obtained as well as simulate,d computer generated, competition
      curves clearly showed that the kidney I-receptors did not exist in two
      independent non-interacting forms. Instead the data suggested that the I-receptor
      was composed of interacting or interconverting receptor entities with different
      affinities for drugs. Monovalent cations such as Cs+ or NH4+ were found to be
      powerful inhibitors of [3H]idazoxan binding to the kidney I-receptors, the ions
      decreasing both the apparent Bmax and affinity of the ligand for the receptor.
      The cations also decreased the affinities of UK-14,304 for both the high and low
      affinity forms of the I-receptor, but the apparent proportions of sites were not
      at all affected by the ions. Moreover, ligand binding to kidney I-receptor were
      not at all affected by non-hydrolyzable guanine nucleotides. It is suggested that
      the binding data reflects functional properties of the I-receptor protein.

PMID- 1349749
TI  - High concentrations of remoxipride in lateral ventricles of rat after systemic
      administration.

PMID- 1349750
TI  - Fifteen years of continued research in psychopharmacology.

PMID- 1349751
TI  - Quantification of SCH 39166, a novel selective D1 dopamine receptor antagonist,
      in rat brain and blood.
AB  - A gas chromatographic method for measuring concentrations of a novel D1
      antagonist SCH 39166 [(-)-trans-6,7,7a,8,9-13b-hexahydro-3-chloro-2-hydroxy-N
      methyl-5- H-benzo[d]naphto(2,1-6)azepine] in rat brain and plasma was developed.
      The method was applied to descriptive pharmacokinetics of two subcutaneous doses
      of SCH 39166 (0.25 mg/kg and 2.5 mg/kg). For comparison, concentrations of the
      "prototype" D1 antagonist SCH 23390 (0.25 mg/kg, SC) [R-(+)-chloro-2,3,4,5
      tetrahydro-3-methyl-5-phenyl-1-H-3-benzazepine] were also measured in plasma and
      brain. SCH 23390 (0.25 mg/kg, SC) had a very short elimination half-life of about
      30 min in plasma, and disappeared in a slightly slower manner from striatum and
      cortex. SCH 39166 (0.25 and 2.5 mg/kg, SC), however, had a longer elimination
      half-life of about 1.5-2.5 h in plasma and brain. Interestingly, the 2.5 mg/kg
      dose of SCH 39166 produced only two-to five-fold increases in maximum
      concentrations in plasma and brain compared to the 0.25 mg/kg dose. The reason
      for this is not clear. The ability of these two doses of SCH 39166 to induce
      catalepsy in the bar test was also evaluated. It was found that SCH 39166 in
      these two doses, unlike SCH 23390, was not cataleptic. In conclusion, these
      pharmacokinetic features of SCH 39166 in the rat should be useful when designing
      experiments with this novel selective D1 antagonist. Furthermore, the longer
      elimination half-life of SCH 39166 makes it a more useful probe in
      pharmacodynamic comparisons of D1 receptor antagonists and classical as well as
      atypical neuroleptics.

PMID- 1349752
TI  - Changes in dopamine D1, D2 and D3 receptor mRNA levels in rat brain following
      antipsychotic treatment.
AB  - The effects of administration of antipsychotic drugs (1-32 days, twice per day)
      on the rat brain mRNA levels of dopamine D1, D2 and D3 receptors has been
      assessed by a novel procedure utilising solution hybridisation with
      oligonucleotides. Saline and sulpiride (10 mg/kg/injection) had no effect on D1,
      D2 and D3 receptor mRNA levels. Haloperidol (1.5 mg/kg/injection) elicited
      increases in D1, D2 and D3 receptor mRNA levels of 100%, 100% and 300%
      respectively, after 32 days and loxapine (2 mg/kg/injection) elicited increases
      of 450%, 150% and 550%, respectively. These results indicate that the up
      regulation of dopamine receptors may be associated with the occurrence of tardive
      dyskinesia but not the clinical mode of action of antipsychotics.

PMID- 1349753
TI  - Effects of irreversible dopamine receptor inactivation on locomotor activity and
      grooming in the 17- and 90-day-old rat.
AB  - Ontogenetic differences in the behavioral recovery of R(-)-propylnorapomorphine
      (NPA) treated rats were assessed following irreversible DA receptor antagonism by
      N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). In the first two
      experiments, 17- and 90-day-old rats were given EEDQ (7.5 or 15.0 mg/kg, IP) or
      vehicle after half the rats were initially treated with the selective DA D-1 and
      D-2 antagonists SCH 23390 and sulpiride. (The sulpiride/SCH 23390 treatment
      protects DA receptors from EEDQ-induced inactivation.) NPA's (0.1 or 1.0 mg/kg)
      effects on locomotor activity and grooming were assessed 1, 2, 4 and 8 days after
      the EEDQ pretreatment. In a third experiment, the effects of habituating the 17-
      and 90-day-old rats to the testing chamber were assessed 1, 2 and 4 days after
      EEDQ pretreatment. In this experiment, some groups received successive treatments
      of saline or NPA prior to behavioral testing. To assess the possible effects of
      drug-sensitization other groups received saline on days 1 and 2 and NPA on day 4.
      In 90-day-old rats, EEDQ eliminated, for up to 4 days, the ability of NPA to
      enhance locomotor activity and depress grooming. Prior treatment with DA
      antagonist drugs was sufficient to protect DA receptors from EEDQ-induced
      inactivation, since these groups exhibited normal behavioral responses after
      challenge with NPA. In contrast, EEDQ did not eliminate, and may have enhanced,
      NPA's effect on the locomotor activity and grooming of 17-day-old rat pups.
      Habituating the rats to the testing chamber decreased the locomotor activity of
      the mature rats, but not the 17-day-old rat pups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1349755
TI  - Behavioural tests of the dopamine depletion hypothesis of neuroleptic-induced
      response decrement.
AB  - This study was carried out to test the hypothesis that neuroleptic-induced within
      session response decrements reflect a fatigue process, resulting from dopamine
      depletion, that is present before the session begins but is masked briefly by
      activational cues present at the start of the session. Response decrementing
      effects of pimozide were examined in rats lever pressing on random interval
      schedules of food reinforcement. An initial experiment was carried out to rule
      out a pharmacokinetic explanation of the response decrement. In a second
      experiment, the response decrement was not exacerbated by an immediately
      preceding period of intense forced motor activity (wheel running). Experiments 3
      and 4 tested two further predictions: that the pimozide-induced response
      decrement should be overcome by removing the animal to its home cage and then
      replacing it in the apparatus (thereby reinstating the activational cues present
      at the start of the session); and that response impairments should be present
      from the outset if the animal is confined in the apparatus prior to the start of
      the session (thereby allowing activational cues to dissipate). Neither prediction
      was confirmed. Overall, the results provide no support for the dopamine depletion
      hypothesis.

PMID- 1349754
TI  - Benzodiazepine-induced sedation and cortisol suppression. A placebo-controlled
      comparison of oxazepam and nitrazepam in healthy male volunteers.
AB  - The sedative and cortisol suppressing properties of oxazepam (45 and 60 mg) and
      nitrazepam (10 and 15 mg) were examined in eight healthy male subjects. The most
      clear differences between oxazepam and nitrazepam were those seen with respect to
      the time course and until maximal effect (Tmax) of the different measurements.
      Nitrazepam showed maximal sedation after 1 h, maximal benzodiazepine level (RRA),
      and reaction time prolongation after 2 h, and maximal cortisol suppression after
      3 h. Oxazepam showed maximal sedation after 2 h, maximal benzodiazepine levels,
      reaction time prolongation and cortisol suppression after 3 h. After
      administration of oxazepam (both doses) a transient return to baseline levels of
      cortisol was demonstrated. Whereas the degree of sedation correlated
      significantly within drug groups with the concurrent benzodiazepine levels, the
      Tmax of sedation was recorded 1 h earlier than the peak blood concentration (RRA)
      for both nitrazepam and oxazepam. The time course for cortisol suppression for
      the two compounds differed clearly from the other measurements and was not
      related to the peak blood concentration.

PMID- 1349756
TI  - What data support our current thrombolytic management of patients with acute
      myocardial infarction?

PMID- 1349757
TI  - Low dose neuroleptanxiolysis in anxiety states.
AB  - 1. In order to prove that neuroleptanxiolysis represents a therapeutical
      alternative in the treatment of patients suffering from anxiety we conducted four
      investigations. 2. In the first study it was experimentally proved with 45
      outpatients suffering from anxiety that fluspirilene (1.5 mg per week) is
      superior to bromazepam (6 mg/day), especially in patients with a high degree of
      somatic anxiety. 3. In the second study the tolerance of fluspirilene (1.5 mg per
      week) was investigated in 1261 patients with anxiety states and psychoreactive
      disorders under controlled and open conditions for a period of six weeks. Side
      effects were found in 11.5% of the patients. All side effects had in common that
      they occurred already within the first few weeks of treatment. 4. In the third
      study investigating the dose-effect relationship 106 patients received either
      0.5, 1.0, or 1.5 mg fluspirilene per week for a period of 6 weeks. The main
      result of this study was the verification of a clear dose-effect relationship. 5.
      The fourth study compared 155 patients who had received long-term treatment with
      fluspirilene (max 1.5 mg/week) and 121 patients with long-term benzodiazepine
      treatment. No differences were found with regard to the frequency and intensity
      of extra-pyramidal disturbances. 6. The therapeutical relevance of the findings
      was emphasized in the general discussion.

PMID- 1349758
TI  - Plasmatic somatostatin as a marker of positive symptoms of schizophrenia.
AB  - 1. Somatostatin displays a regulatory function on several aminergic
      neurotransmitters, including dopamine. In addition, decreased CSF levels of the
      peptide has been found in Schizophrenia and other neuropsychiatric disorders. 2.
      In the present work, we have investigated levels of plasmatic somatostatin in a
      sample of 50 schizophrenic patients compared with a normal control group. 3.
      Somatostatin was increased in the patient group (p less than 0.01) as a whole but
      statistical analysis revealed that the increase was associated with the presence
      of positive symptoms (Factorial Analysis) with a significant correlation,
      specially with delusion and hallucination scores in the Andreasen rating scales.

PMID- 1349759
TI  - Central dopamine involvement in experimental gastrointestinal injury.
AB  - 1. Rats were prepared with intracerebral cannulas for microinjection of test
      compounds into various brain regions. 2. Selective dopamine D1 agonists
      (SKF38393, SKF75670C) and a D1 antagonist (SCH23390) were injected into the cell
      body regions of the nigrostriatal, mesolimbic and mesocortical dopamine tracts or
      into a terminal field of these tracts (caudate nucleus, central nucleus of the
      amygdala and medial prefrontal cortex) prior to gastric ulcer induction by cold
      restraint stress or duodenal ulcer induction by cysteamine. 3. The dopamine D1
      agonists reduced both stress gastric ulcers and duodenal lesions most
      significantly when given into either the cell body region or a terminal field of
      the mesolimbic DA tract with much less effects seen for the nigrostriatal tract.
      4. No effects were seen upon infusion of the agonists into the mesocortical cell
      body or terminal field regions. 5. The D1 antagonist worsened both stress-induced
      gastric lesions and duodenal lesions if given into mesolimbic regions and, to a
      much lesser extent when injected into the nigrostriatal tract. 6. No effect of
      the D1 antagonist was seen upon administration into the mesocortical tract. 7.
      Central dopamine D1 receptors, particularly in the mesolimbic DA tract, appear to
      be involved in mediating the gastrointestinal consequences of exposure to stress.

PMID- 1349760
TI  - The effect of ritanserin on treatment-resistant neuroleptic induced akathisia:
      case reports.
AB  - 1. The authors report three cases of neuroleptic induced akathisia resistant to
      treatment with anticholinergics, benzodiazepines and betablockers. 2. All three
      patients were treated with Ritanserin 10 mg bid and improved rapidly and
      substantially. 3. Discontinuation of Ritanserin led to a recurrence of akathisia.

PMID- 1349761
TI  - Plasma concentrations of regulatory peptides in obesity following modified sham
      feeding (MSF) and a liquid test meal.
AB  - Plasma concentrations of regulatory peptides were monitored in groups of obese
      and normal-weight subjects following modified sham feeding and a liquid fatty
      meal. Following modified sham feeding a significant increase in immunoreactive
      cholecystokinin (CCK) in plasma was recorded in both groups. In the obese
      subjects, however, the concentrations following sham feeding were significantly
      lower than in normal-weight subjects, and the initial part of the response was
      negative. Basal and modified sham feeding stimulated immunoreactive pancreatic
      polypeptide (PP) concentrations in plasma did not differ between the groups.
      After the liquid fatty meal plasma CCK concentrations increased similarly in both
      groups. In contrast immunoreactive neurotensin and somatostatin concentrations
      following the meal were lower in the obese group, and a changed concentration
      time pattern for somatostatin was observed in the obese group. Postprandial
      concentrations of PP and immunoreactive gastrin were not different in the groups.
      The results indicate that the plasma concentration patterns of CCK, somatostatin
      and NT are disarranged in obesity. The changes may promote rapid propulsion and
      absorption of ingested food, and facilitate deposition of fat in adipose tissue
      in obesity and thus may be of pathophysiological importance.

PMID- 1349762
TI  - From alveoli back to bronchi. Contribution of bronchoalveolar (BAL) and bronchial
      (BL) lavage to the understanding of bronchial disease. International workshop.
      Verno, Italy, April 19-21, 1990.

PMID- 1349763
TI  - Meta-analysis for 2 x 2 tables: a Bayesian approach.
AB  - This paper develops and implements a fully Bayesian approach to meta-analysis, in
      which uncertainty about effects in distinct but comparable studies is represented
      by an exchangeable prior distribution. Specifically, hierarchical normal models
      are used, along with a parametrization that allows a unified approach to deal
      easily with both clinical trial and case-control study data. Monte Carlo methods
      are used to obtain posterior distributions for parameters of interest,
      integrating out the unknown parameters of the exchangeable prior or 'random
      effects' distribution. The approach is illustrated with two examples, the first
      involving a data set on the effect of beta-blockers after myocardial infarction,
      and the second based on a classic data set comprising 14 case-control studies on
      the effects of smoking on lung cancer. In both examples, rather different
      conclusions from those previously published are obtained. In particular, it is
      claimed that widely used methods for meta-analysis, which involve complete
      pooling of 'O-E' values, lead to understatement of uncertainty in the estimation
      of overall or typical effect size.

PMID- 1349764
TI  - [Imidazopyridines, an alternative to benzodiazepines].
AB  - Imidazopyridines are a new class of molecules comprising so far a pure hypnotic
      agent--zolpidem, and an anxiolytic alpidem. The biochemical mode of action and
      the clinical characteristics are discussed with particular reference to
      benzodiazepines.

PMID- 1349765
TI  - [Advances in the understanding of obesity. Report of the third congress of the
      European Association for the Study of Obesity].

PMID- 1349766
TI  - [Treatment of rheumatoid polyarthritis with salazosulfapyridine].

PMID- 1349767
TI  - IL-4 decreases IFN-gamma-induced endothelial ICAM-1 expression by a
      transcriptional mechanism.
AB  - Intercellular adhesion molecule-1 (ICAM-1, CD54) is a cell surface ligand for LFA
      1 (CD11a/18). Several cytokines, such as IL-1, TNF-alpha or IFN-gamma, have been
      shown to increase the ICAM-1 expression on cultured endothelial cells. Here we
      show that IL-4 decreases the IFN-gamma-induced ICAM-1 expression on an
      endothelial cell line (EA.hy 926), whereas IL-4 alone has practically no effects
      on ICAM-1 expression. The down-regulative effect was also seen at the mRNA level
      suggesting that this regulation process is transcriptional. At the same time IL-4
      was unable to alter the TNF-alpha-induced ICAM-1 up-regulation. Both IFN-gamma
      and TNF-alpha are able to decrease the proliferation of the endothelial cell
      line, but IL-4 could not modify this response when added together with the other
      cytokines. Taken together we show in this paper that IL-4 decreases IFN-gamma but
      not TNF-alpha-induced up-regulation of ICAM-1 expression on EA.hy 926 cells.

PMID- 1349768
TI  - Development of the non-palindromic adaptor polymerase chain reaction (NPA-PCR)
      for the amplification of alpha- and beta-chain T-cell receptor cDNAs.
AB  - We have developed a highly efficient new method for the amplification of alpha-
      and beta-chain human T-cell receptor (TCR) cDNAs. This method is designated non
      palindromic adaptor polymerase chain reaction (NPA-PCR). cDNA was synthesized
      from total RNA isolated from mononuclear leucocytes, using either an oligo (dT)15
      NotI or a C alpha-NotI or a C beta-NotI primer and RNase H-negative reverse
      transcriptase. The double-stranded cDNA was ligated with the non-palindromic
      adaptors EcoRI-XmnI [d(ATTCGAACCCCTTCG)] and XmnI G strand [d(pCGAAGGGGTTCG)]
      (phosphorylated), which resulted in the addition of the EcoRI-XmnI site in both
      5' and 3' ends. These two non-palindromic adaptors, EcoRI-XmnI and XmnI G strand,
      are complementary to each other and both are required for ligation. The EcoRI
      XmnI adaptor was removed from the 3' end by treatment with NotI restriction
      nuclease, whereas it was retained at the 5' end. The non-palindromic adaptor
      EcoRI-XmnI was used as the 5' amplification primer. C alpha or C beta constant
      region primers were used as 3' amplification primers. The amplified cDNAs were
      cloned and the plasmids were used to transform DH5 alpha competent cells. Over
      1000 white colonies per 0.1-0.25 micrograms of total RNA or per 10,000 to 50,000
      human peripheral blood mononuclear cells were obtained after amplification of
      either the alpha- or the beta-chain TCR cDNAs. Between 40 and 62% of the colonies
      (range from five donors) were positive after screening with either a C alpha or a
      C beta probe, located 5' to the C alpha and C beta amplification primers. A total
      of 50 amplified alpha- or beta-chain cDNA positive clones from two normal donors
      were randomly chosen and sequenced, and the sequences obtained were typical of
      alpha beta TCR. Two new J alpha gene segments were identified. Approximately 30%
      of the alpha-chain positive clones have 5' untranslated region, and most of the
      remaining alpha- or beta-chain TCR clones started from the initiation codon or
      near the 5' end. NPA-PCR has several advantages over existing PCR methods for the
      amplification of cDNAs with unknown or variable 5' end, such as the T-cell
      antigen receptors and the immunoglobulins. Among these advantages is that only
      one 5' end extension primer is required. Because of the large number of TCR V
      alpha and V beta families, a large number of different 5' end primers are
      required for amplification of alpha beta TCR cDNAs by conventional PCR.

PMID- 1349769
TI  - T cells cloned from human rheumatoid synovial membrane functionally represent the
      Th1 subset.
AB  - The presence of activated T cells in the synovial membrane of patients with
      rheumatoid arthritis (RA) suggests a role for these cells in the pathogenesis of
      the disease. Recent evidence indicates that human T cells may fall into
      functional categories dependent on their cytokine profile and cytotoxic capacity.
      The human Th1 subset is cytolytic and produces high levels of IFN-gamma whereas
      the Th2 type of T cell produces IL-4. In order to investigate whether Th1 or Th2
      type cells are present in the inflammatory synovial membrane in RA, a panel of
      synovial membrane derived T-cell clones (n = 19) was generated and studied
      functionally. Anti-CD3-induced cytotoxicity assays were performed to demonstrate
      the cytotoxic potential of clones. Except for two, all clones were cytolytic in
      this test. Clone cells were activated to initiate cytokine production and
      assessment of the cytokine levels showed that all clones produced large amounts
      of IFN-gamma (18 out of 19 clones: over 50,000 pg/ml) whereas IL-4 was absent or
      present in minimal amounts (17 out of 19 clones: less than 1000 pg/ml). The
      production of IL-1, IL-2 and IL-6 was variable. The functional characteristics of
      the clones studied indicate that they may resemble the Th1 subtype of T cells.
      Our data suggest a relation between Th1-type functions the chronic inflammation
      characteristic of RA.

PMID- 1349770
TI  - Oral health in preschool children living in Sweden. Part II--A longitudinal
      study. Findings at three years of age.
AB  - Scientific epidemiological studies of dental health in children three years of
      age are relatively few in Sweden. The aim of this study was to describe the oral
      health of three-year-old children living in Sweden, with special reference to
      immigration and failure to attend health examinations. All of 671 children
      requested to take part in an earlier investigation (Wendt et al. 1991) were
      invited for a new dental examination at three years of age. A total of 632
      children were examined. At the age of three years 71.7 per cent of the children
      were caries free. Of the children with caries, 33.5 per cent were immigrants and
      of the total number of immigrants, 50.5 per cent had caries compared to 21.9 per
      cent of the non-immigrant children. Among those children, who failed to attend
      the earlier investigations at one or two years of age, 61.5 per cent had caries
      at the age of three. Compared to studies on dental health in three-year-old
      children from the 70's and 80's (Hugoson et al. 1986), this study shows that
      dental health in three-year-old children has not improved significantly during
      the last decade. Furthermore, this study supports the suggestion that special
      preventive dental programmes should be developed for immigrant children and that
      extra attention should be paid to children who fail to attend health examinations
      and their families.

PMID- 1349771
TI  - 28th annual congress of the Swedish Dental Society. November 13-15, 1991.
      Abstracts.

PMID- 1349772
TI  - [Death caused by antidepressive agents and neuroleptics].

PMID- 1349773
TI  - Unraveling the knots in plant development.
AB  - Homeobox genes, first discovered from studies of homeotic mutations in
      Drosophila, have recently been found in plants. The proteins encoded by homeobox
      genes thus join the ranks of other animal transcription factors that have plant
      developmental counterparts, suggesting that even though plant and animal
      development are very different, regulatory mechanisms that direct development may
      be shared among all higher eukaryotes. The role of homeobox genes in plants
      remains elusive; nonetheless, gain-of-function mutations of one homeobox gene,
      Knotted, profoundly affect development. The phenotype suggests that ectopic
      expression of Knotted in leaves causes cells to take on alternative fates.

PMID- 1349774
TI  - Detection, classification and 3D reconstruction of biological macromolecules on
      hypercube computers.
AB  - In this work we present results of the mapping on hypercube computers of some of
      the key steps involved in the procedure for 3D structural determination from
      transmission electron microscopy images. The goal is the introduction of parallel
      processing tools in the field of electron microscopy image processing. We show
      how the rich topology of the hypercube, combined with an efficient programming
      strategy, allows for order-of-magnitude increase in computational capacity for
      such time-consuming tasks as calculation of multidimensional FFT's, cross
      correlation coefficients, fuzzy partitioning functionals and the filtered back
      projection 3D reconstruction method.

PMID- 1349775
TI  - Inhibition of cellular autophagy in proximal tubular cells of the kidney in
      streptozotocin-diabetic and uninephrectomized rats.
AB  - To examine the significance of anti-catabolism in renal hypertrophy, cellular
      autophagy was investigated by electron microscopic morphometry in proximal
      tubular cells (PTCs) of the outer cortex of the rat kidney after the induction of
      diabetes mellitus by streptozotocin (STZ) and after unilateral nephrectomy. Adult
      male Sprague-Dawley rats were divided into three groups and killed by retrograde
      perfusion fixation, 1, 2 and 3 days after the induction of diabetes (group D; n =
      24), after unilateral nephrectomy (group N; n = 24) and after combined treatment
      (group DN; n = 24). Untreated, age-matched litter mates served as controls (group
      C; n = 24). By comparison with these controls, the left kidney to initial body
      weight ratio was increased by 8, 23, and 15% in group D animals, by 8, 23, and
      24% in group N animals, and by 10, 21, and 25% in group DN animals at the first,
      second and third day, respectively. Quantitative evaluation of large test areas
      showed that the volume and numerical densities of autophagic vacuoles (AVs) in
      PTCs were significantly lower in these hypertrophed kidneys than in the controls.
      The average reduction in AV volume density was about 65% in group D animals,
      about 50% in group N animals and about 75% in group DN animals. These data show
      that autophagic degradation of cytoplasmic components in PTCs is inhibited in
      renal hypertrophy independently of the growth stimulus, i.e. uninephrectomy or
      diabetes. Since insulin per se inhibits cellular autophagy in PTCs, the expected
      effect of insulin dificiency seems to be counteracted by as yet undefined stimuli
      that may be related to metabolic work load.

PMID- 1349776
TI  - Cellular autophagy in proximal tubules of early diabetic rats following insulin
      treatment and islet transplantation.
AB  - The influence of insulin treatment (group 1) and allogenic islet transplantation
      (group 2) on renal cellular autophagy were evaluated in adult Lewis rats in the
      early phase of streptozotocin-induced diabetes mellitus--a condition in which
      autophagy is inhibited and renal mass is increased. Three days after insulin
      treatment or islet transplantation (IT), the right kidney was resected and
      cortical tubular tissue was examined by quantitative electron microscopy. In
      group 1, the volume and numerical densities of autophagic vacuoles (AVs)
      increased by 70% and 80% respectively in the proximal tubular cells compared with
      saline-injected controls. The additive effect of unilateral nephrectomy (Ux) on
      cellular autophagy was investigated 1 or 2 days after Ux. Compared with the
      resected right kidney, the volume and numerical densities of AVs in the remnant
      left kidney decreased by 49% and 43% in the insulin-treated rats, and by 43% and
      39% in the saline-injected diabetic animals. In group 2, the volume and numerical
      densities of AVs increased by 45% and 44% in parenchyma regressing from diabetic
      hypertrophy after IT, compared with sham-operated controls. After Ux, the volume
      and numerical densities of AVs decreased by 49% and 43% in IT rats, and by 41%
      and 53% in the still diabetic sham-operated animals. The data show that
      inhibition of cellular autophagy in the proximal tubules of the early diabetic
      kidney can be reversed by insulin replacement, despite the fact that insulin per
      se inhibits cellular autophagy in the nondiabetic kidney.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1349777
TI  - Vitamin A deficiency and inflammation: the pivotal role of secretory cells in the
      development of atrophic, hyperplastic and metaplastic change in the tracheal
      epithelium in vivo.
AB  - We showed previously that the proliferation of hamster airway secretory cells
      decreases during vitamin A deficiency (VAD) but later increases when submucosal
      inflammation develops (Virchows Arch [B] 59:231-242, 1990). This observation has
      important biological implications since two morphological extremes (atrophy and
      quiescence versus hyperplasia and hyperproliferation) are reported in the
      literature for VAD tracheal epithelium in vivo. In the present study,
      histological slides of tracheal rings from 35-day-old control and VAD hamsters
      (Virchows Arch [B] 45:197-219, 1984) were reviewed again. Rings from VAD hamsters
      were selected based on the absence or presence of a florid submucosal
      inflammation. Quantitative analyses were made on the cartilaginous part of rings
      from the anterior third of the trachea. When inflammation was absent, a
      mucociliary pseudostratified epithelium was, for the most part, maintained. The
      mitotic rate (MR, 6 h colchicine blockade) of secretory cells was markedly
      reduced (29-fold) but that of basal cells was not changed significantly.
      Moreover, cell density was not changed by VAD but ciliated cells and secretory
      cells were decreased and basal cells were increased, proportionally. We call this
      "minimal morphological change." Thinning (atrophy) of the minimally changed
      epithelium was associated with focal cell sloughing. Small scattered foci of
      epidermoid metaplasia (multiple layers of highly keratinized cells which were
      extremely flat, so that the epithelium was thin and attenuated) were also seen.
      We call this "atrophic epidermoid metaplasia." When inflammation was present,
      hyperplastic changes (stratification and epidermoid metaplasia) predominated and
      cells were in mitosis at all epithelial levels (low, middle, superficial) except
      in the most superficial (terminally differentiated) squames. The tracheal
      epithelium was thickened and hypercellular. The cells were piled up at the
      stratified lesions, and epithelial height, cell density and epithelial MR were
      significantly increased compared with the non-inflamed VAD epithelium. The
      effects of VAD and inflammation on cell proliferation were analyzed further by
      studying 7 h bromodeoxyuridine (BrdU) labelling patterns of cells in VAD tracheal
      epithelium, with and without submucosal inflammation. In addition, inflammation
      was induced in "minimally changed epithelium" by mild mechanical injury. The BrdU
      labelling patterns confirmed that DNA synthesis by secretory cells is reduced
      markedly by VAD. However, this suppression is overidden by the influx of
      inflammatory cells (the nature of the stimulus is unknown). The results indicate
      that the morphological contrasts (atrophy and hyperplasia) seen in the trachea
      during VAD in vivo are related to extremes in proliferation rates of tracheal
      secretory cells, regulated by VAD alone (minimal replication) and by inflammation
      (maximal replication).

PMID- 1349778
TI  - Immunocytochemical observation of paraquat-induced alveolitis with special
      reference to class II MHC antigens.
AB  - The expression of class II major histocompatibility complex (MHC) antigens on
      alveolar epithelial cells and macrophages was investigated immunocytochemically
      in paraquat-induced alveolitis in the rat lung. Until 2 days after paraquat
      injection, class II MHC antigens were expressed on the type II alveolar
      epithelium without any inflammatory cellular infiltration. From the 4th to the
      7th day after paraquat injection, class II MHC antigen-positive macrophages
      increased in the alveolar spaces, whereas the expression on the type II alveolar
      epithelium became obscure. Over 10 days after the injection, interstitial
      fibrosis progressed and the intra-alveolar inflammatory infiltrates decreased.
      Epithelial cells lining the thickened fibrous septa no longer expressed class II
      MHC antigens. These results suggest that chemical stimuli can induce class II MHC
      antigen expression on the type II alveolar epithelium in the early stage of
      cellular injury, followed by inflammatory infiltration and interstitial fibrosis.

PMID- 1349779
TI  - An ultrastructural study of proliferative nephritis induced experimentally by a
      monoclonal antibody against mesangial cells: replacement of mesangial cells by
      cells of the monocyte-macrophage system.
AB  - An experimental nephritis accompanied by transient proteinuria can be produced by
      an intravenous injection of the monoclonal antibody, 1-22-3, raised against
      isolated rat glomeruli. The present study deals with the ultrastructural changes
      in the glomeruli in rats after the injection of this antibody. At 2 h after
      injection, all the mesangial cells had completely degenerated and neutrophils
      invaded most mesangial areas. Monocytes occupied the vacant mesangial areas at 24
      h and gradually increased in number over the next 4 days. At 4 and 6 days,
      macrophage-like cells, possibly derived from monocytes, underwent frequent
      mitosis, resulting in a remarkable proliferation of these cells. The
      interpretation of these cells as macrophages was strongly supported by the fact
      that they contained previously injected latex particles in large numbers. From 2
      to 4 weeks after injection, the macrophage-like cells gradually transformed into
      cells indistinguishable from normal mesangial cells. In the present experimental
      nephritis where all mesangial cells were initially destroyed, cells of the
      monocyte-macrophage system appear to play a leading role in the pathogenesis of
      the ensuing proliferative glomerulonephritis, and represent the source of the
      replacing mesangial cells.

PMID- 1349780
TI  - HLA-DR antigen- and S-100 protein-positive dendritic cells in esophageal squamous
      cell carcinoma--their distribution in relation to prognosis.
AB  - The distribution of immunohistochemically labeled HLA-DR antigen- and S-100
      protein-positive dendritic cell (DR+DC and S100+DC) was investigated in 59 human
      esophageal squamous cell carcinomas (SCCs). A dense infiltration of both DR+DC
      and S100+DC was detected in 11, only DR+DC in two, and only S100+DC in one. In
      the remaining 45 tumors infiltrating DC were sparse. By means of double
      immunostaining or the mirror section method, three different types of DC, namely
      S-100-negative and HLA-DR-positive DC(S100-DR+DC), S-100-positive and HLA-DR
      negative DC(S100+DR-DC) and double-positive DC(S100+DR+DC) were clearly
      identified. With regard to postoperative survival, these patients with tumors in
      which there was a dense infiltration of DR+DCs and/or S100+DCs showed a
      significantly better survival rate than those in which DC were sparse (DR+DCs - P
      less than 0.001; S100+DCs - P less than 0.01). These results indicate that DC
      infiltration may be a prognostic factor in esophageal SCCs.

PMID- 1349781
TI  - Colonic cell proliferation and growth fraction in young, adult and old rats.
AB  - Colonic epithelial proliferation was investigated in three groups of rats, aged
      3, 60 and 121 weeks. As reported in previous work, the crypts were markedly
      longer in the young rats, and the number of labelled cells per crypt was
      significantly greater. There was an upward movement of the marker positions
      derived from the distribution of labelled cells within the crypt of the young
      rats. This was a consequence of the increased crypt length, so that the growth
      fraction, as expressed as a percentage of crypt length, was the same. The
      proliferative changes between the young rats and the other aged rats were
      therefore effected by altering the size of the crypts, while maintaining the
      kinetic organisation. There was no evidence of any proliferative changes or
      changes in the growth fraction when the colons of the old rats were compared with
      those of the 60 week old rats.

PMID- 1349782
TI  - Endothelial cell protrusions in the rat aortic wall. Immunocytochemical evidence
      for an alternative transendothelial passage of plasma proteins.
AB  - Focal morphological changes in the endothelial lining were observed in the aortic
      wall of control rats. They consisted of endothelial cytoplasmic projections and
      vacuolar structures protruding towards the luminal space and containing electron
      dense material. Some of these structures were observed to open into the
      subendothelial space. Endogenous albumin was detected in these compartments by
      applying protein A-gold immunocytochemistry to thin tissue sections of
      glutaraldehyde-fixed, Lowicryl-embedded aortic segments. The labelling was mainly
      distributed along the plasma membrane of the projections as well as over the
      dense content of the endothelial protrusions. The presence of endogenous albumin
      in these endothelial structures, together with their opening into the
      subendothelial space, suggests a role for these structures in an alternative
      transendothelial transport of albumin.

PMID- 1349784
TI  - Fimbriae and membranes on Haemophilus parasuis.
AB  - In the electron microscope an additional layer (glycocalix) of the cell wall and
      fimbriae on Haemophilus parasuis were shown in thin sections of the infected CAM
      which have their origin on the CM of the Haemophilus parasuis-cells. No
      fimbriation was seen after conventional cultivation.

PMID- 1349783
TI  - [The characteristics of the anxiolytic action of benzodiazepine and non
      benzodiazepine tranquilizers in different tests of anxiety].
AB  - In experiments on rats the presence or absence was studied of the phenomenon of
      potentiation of anxiolytic action, estimated by the time of the animal stay in
      the light part of the chamber in tests of avoidance of "the lighted ground" or
      "menacing situation" at combined application of the pairs of substances of
      benzodiasepine and non-benzodiasepine series (elenium, indoter, campiron and
      campironin). Spectra of their neurochemical activity were determined in
      experiments on neurones of isolated spinal ganglia of rats with intracellular
      biopotentials records. It has been established that GABA-potentiating action of
      indoter and elenium, dopamine-negative action of campiron and campironin are
      significant in their anxiolytic action in the states of alarm of aversive genesis
      of different modalities. Serotoninmimetic effect of non-diasepine tranquilizers
      is of functional significance in the test of avoidance of "the lighted ground",
      but not of the "menacing situation". It is suggested that differences of
      neurochemical mechanisms of anxiolytic action of the tested tranquilizers testify
      to different neurochemical profiles of the neuronal "matrices" of the studied
      states of alarm.

PMID- 1349785
TI  - On the stimulation of soluble and particulate guanylate cyclase in the rat brain
      and the involvement of nitric oxide as studied by cGMP immunocytochemistry.
AB  - The localization of the particulate and soluble guanylate cyclase in the rat
      brain was studied using cGMP-immunocytochemistry. The cGMP was fixed to tissue
      protein using a formaldehyde fixative, and an antibody against cGMP was used
      which was raised against a cGMP-formaldehyde-thyroglobulin conjugate. We used the
      atrial natriuretic factor (ANF) as a model compound to stimulate the particulate
      enzyme and sodium nitroprusside (SNP) to stimulate the soluble enzyme. Sequential
      immunostaining for cGMP and glial fibrillary acidic protein (GFAP) showed that
      the great majority of the ANF-responsive, cGMP-producing cells were astrocytes.
      These ANF-responsive cells were found in discrete parts of the CNS; not all
      astrocytes in these regions were responsive to ANF. SNP stimulated cGMP in
      abundantly present neuronal fibres throughout the CNS; few neuronal cell bodies
      showed increased cGMP production after SNP. Moreover, SNP also raised cGMP in
      astrocytes, however, not all astrocytes showed the response to SNP. These results
      suggest that cells might be present in the CNS which contain both the soluble and
      the particulate guanylate cyclase. It was demonstrated that in the immature
      cerebellum, the cGMP was raised in glial structures in response to N-methyl-D
      aspartate (NMDA), ANF, SNP, and kainic acid. The response to NMDA and kainic acid
      was sensitive to inhibition of the nitric oxide synthesis from L-arginine by NG
      methyl-L-arginine. Surprisingly the response to ANF localized in the molecular
      layer and the granular layer was also sensitive to inhibition by NG-methyl-L
      arginine, whereas the response to ANF in the deep nuclei was not. A small
      depolarization induced by 10 to 20 mmol/l K+ induced an increase in cGMP in
      chopped hippocampus tissue which showed a biphasic temporal characteristic. The
      initial, fast (30 sec), peak was shown to be localized in varicose fibres
      throughout the hippocampus, whereas the slower response (10 min) was localized in
      astrocytes. These studies demonstrate that the different enzymes which synthesize
      cGMP are differently localized. However, there is also a time dependency in the
      activation of the guanylate cyclases, which becomes apparent in different
      structures at different times. The possible role of cGMP as a regulator of ion
      homeostase is discussed.

PMID- 1349786
TI  - Analysis of HLA-DQA1 in Japanese patients with type 1 diabetes mellitus, using
      DNA-PCR-RFLP typing.
AB  - DNA-polymerase chain reaction(PCR)-RFLP(restriction fragment length polymorphism)
      typing of the DQA1 gene was performed on 39 patients with type 1 diabetes and 30
      controls. Analysis of the frequency of the subtypes of DQA1 alleles, using the
      DNA-PCR-RFLP typing technique, showed that the DQA1*0301 subtype was most
      strongly associated with the disease (97.4% vs 56.7%, R.R. = 19.8, pc less than
      0.00005). These results indicated that DQA1*0301 may determine the disease
      susceptibility in the Japanese. In addition, we analyzed the frequency of the
      subtypes of DQA1 genes in the ten patients carrying the DRW8-DQW8 haplotype, and
      found that at least eight of them (80%) were classified as having DQA1*0301. The
      DRW8-DQW8-DQA1*0301 may be one of the susceptible haplotypes among the Japanese.

PMID- 1349787
TI  - Ontogenic expression of somatostatin-messenger RNA in the intestinal tract of
      neonatal rats.
AB  - Ontogenic expression of somatostatin (SRIF) -messenger RNA (mRNA) in the
      gastrointestinal tract was examined in neonatal rats aged from 1 day preterm to
      60 days postpartum in comparison with that in the hypothalamus. SRIF-mRNA in the
      hypothalamus was already expressed in prenatal rats and its developmental change
      was relatively small. In contrast, a unique pattern of SRIF-mRNA expression was
      seen in the different intestinal regions, gastric antrum, duodenum, jejunum and
      colon. In the duodenum, SRIF-mRNA level was low at birth, markedly increased
      during the postnatal 3 days and declined to the previous level by day 21. Jejunal
      SRIF-mRNA was found in neonates but progressively decreased in a similar way to
      duodenum. On the contrary, gastric SRIF-mRNA level, which was low during early
      development, rose rapidly to a peak on day 21 and gradually declined to an adult
      level. In the colon age-related change was not conspicuous, remaining at a low
      level. These results indicate that (1) expression of SRIF gene in the intestinal
      tract is regulated by local factor(s) as well as developmental stage, and (2)
      shift of SRIF-mRNA pattern occurs during weaning from the duodenum-dominant
      infantile pattern to the gastric-dominant adult pattern.

PMID- 1349788
TI  - Reassessment of the role of theophylline in the current therapy for nocturnal
      asthma.
AB  - BACKGROUND: Symptoms of asthma commonly increase at night for a variety of
      reasons. While different options are available for the management of nocturnal
      asthma, theophylline has maintained a prominent role in treating this problem,
      and it is widely promoted as a first-line agent. Very recent reports stress the
      use of anti-inflammatory agents as the drugs of choice for the long-term
      treatment of asthma. METHODS: Using the key words "asthma," "theophylline,"
      "bronchodilators," "adrenal cortex hormones," "beclomethasone," "triamcinolone
      acetonide," and "disodium cromoglycate," the MEDLINE files were searched from
      1982 to the present. Articles dating before 1982 were accessed from cross
      reference of the more recent articles. RESULTS: Sustained-release theophylline
      preparations are effective in decreasing the rate of exacerbations of nocturnal
      asthma symptoms, but theophylline has risks of major toxicity and serum
      concentrations must be monitored. Inhaled corticosteroids are also useful in
      controlling nocturnal asthma, and they reduce inflammation, which is the basic
      problem in asthmatics. Inhaled anticholinergics and oral controlled-release
      albuterol are also helpful in reducing symptoms of nocturnal asthma. CONCLUSIONS:
      A suggested approach to managing nocturnal asthma includes corticosteroids
      inhaled through a spacer device at optimum doses, adding inhaled albuterol or
      oral sustained-release albuterol and then ipratropium with a spacer. If control
      is not maintained with this regimen, sustained-release theophylline may add
      benefit to inhaled steroid therapy in reducing nighttime asthma symptoms. Long
      acting inhaled beta 2 agonists show promise and could be the adjunctive treatment
      of choice when they become available in the United States.

PMID- 1349789
TI  - Hypnotherapy for reflex sympathetic dystrophy.
AB  - Reflex sympathetic dystrophy (RSD) is an unusual, debilitating, chronic pain
      syndrome thought to be the result of a continuous excessive discharge of regional
      sympathetic nerves. Supportive and stress-reduction psychotherapies are commonly
      recommended as adjunctive treatments. Biofeedback is a more direct symptomatic
      treatment. Although hypnotherapy is effective in altering sympathetic reflex and
      pain responses, there are no reports of its use for the treatment of RSD. This
      article reviews some promising results of hypnotherapy with three RSD sufferers.
      I discuss the role of hypnotherapy as a supportive adjunct to medical treatment.
      I also explore the possible role of hypnotherapy as a complementary treatment.

PMID- 1349791
TI  - The paradox of beta-adrenergic blockade for the management of congestive heart
      failure.
AB  - PURPOSE: To review the current data regarding the use of beta-adrenergic blockers
      for the treatment of congestive heart failure. MATERIAL AND METHODS: Relevant
      studies published between 1975 and 1991 were reviewed. Key data from each study
      were extracted. The significance of conclusions reached by each author(s) was
      identified. RESULTS: beta-adrenergic blockade, although still considered an
      investigational therapy for the treatment of congestive heart failure, has been
      proven in several studies to improve ventricular function, including myocardial
      contractility and relaxation. In addition, since beta-blockade up-regulates
      myocardial beta-receptors, the myocardium becomes more responsive to graded doses
      of beta-agonists. Speculation regarding the possible mechanisms of these effects
      is presented. In addition, since beta-blockers have been shown to reduce
      neurohormonal activation, they may have a beneficial effect on survival. Although
      small pilot studies or subgroup analysis of larger studies suggest beta-blockade
      therapy improves survival in heart failure, this has yet to be proven. Large
      prospective trials are warranted to study this issue. CONCLUSIONS: As current
      data suggest, beta-blockers improve ventricular function and reduce neurohormonal
      activation in heart failure. beta-blockers should be considered as adjunctive
      therapy in patients with congestive heart failure. In addition, future studies
      are warranted to better elucidate their effects on ventricular function and
      survival.

PMID- 1349790
TI  - Incidence of liver toxicity associated with the use of flutamide in prostate
      cancer patients.
AB  - PURPOSE: The incidence of flutamide-related liver toxicity was studied in 1,091
      consecutive patients treated for stage C or D prostate cancer with the
      antiandrogen flutamide and the luteinizing hormone-releasing factor (LHRH)
      agonist [D-Trp6, des-Gly-NH2(10)] LHRH ethylamide. PATIENTS AND METHODS: Liver
      function tests, namely measurement of serum aspartate amino-transferase (AST) and
      alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase, gamma
      glutamyl transpeptidase (gamma-GT), and prothrombin and thromboplastin times,
      were performed at 4, 8, and 12 weeks and every 3 months thereafter. Clinical
      signs and symptoms of liver dysfunction were also sought. The causal link between
      the antiandrogen used and liver injury was assessed on the basis of the temporal
      relationship with the use of the drug in the absence of other possible causes
      and, in two patients, through rechallenge of the putative causative drug after a
      period of normalization of liver function. RESULTS: An increase in AST and ALT at
      fourfold or more above upper normal limits was observed in only four patients
      (0.36%). Total serum bilirubin and alkaline phosphatase were elevated in only one
      patient at 126 mmol/L and 640 IU/L, respectively. Among the four patients, only
      two developed clinical manifestations of liver disease (0.18%). Biopsy was
      performed in one patient, and the histopathologic findings showed a mixed pattern
      of cytotoxic and cholestatic changes. All clinical and biologic manifestations of
      liver toxicity rapidly disappeared upon discontinuation of flutamide alone. No
      sequelae were observed in the long-term follow-up at 18, 22, 31, and 62 months.
      The 1,087 remaining patients experienced no or mild (less than fourfold upper
      normal limit) and transient elevation in aminotransferase serum levels during the
      first 6 months of treatment, with normalization at later time intervals.
      CONCLUSION: Despite the fact that the cases reported so far, along with our large
      series, indicate that the incidence of flutamide-induced liver toxicity is very
      low, we recommend serial blood aminotransferase measurements at 2 and 4 weeks of
      treatment in order to detect early signs of possible flutamide-induced hepatic
      injury, thus avoiding the low potential risk of clinically significant liver
      toxicity.

PMID- 1349792
TI  - The synthesis and antineoplastic activity of 2'-deoxy-nucleoside-cyanoboranes in
      murine and human culture cells.
AB  - The guanine, inosine, adenine and cytidine deoxyriboside cyanoboranes proved to
      be cytotoxic and possess in vivo antineoplastic activity against murine and human
      single cells and cultured cells derived from solid tumor lines. The agents
      preferentially inhibited DNA synthesis in Tmolt3 leukemic cells. The enzyme sites
      of drug inhibition of two active derivatives were DNA polymerase-alpha and de
      novo purine synthesis at the regulatory sites, PRPP amido transferase and IMP
      dehydrogenase. Moderate inhibition by the agents of TDP kinase and ribonucleoside
      reductase activities also occurred. Kinetic studies showed that IMP dehydrogenase
      activity was inhibited the earliest of all of the enzymes affected by the drugs.
      The d(ATP) pools were also reduced by drug treatment. DNA strand scission was
      evident after 24 hr incubation at 100 microM of drug. The 14C-cytidine
      cyanoborane drug was rapidly taken up over 6 hr and most effective uptake was
      shown by rapidly dividing cells. The drug was bound to DNA, RNA and protein in
      Tmolt3 leukemic cells.

PMID- 1349793
TI  - Prediction of drug resistance in human tumors using immunohistochemical
      techniques.
AB  - An in vitro chemosensitivity testing procedure based on the immunodetection of
      protein products which reflect the expression of various tumor resistance
      mechanisms is proposed. This protocol may be of predictive value in choosing
      drugs which should be selected for chemotherapy, and avoiding drugs which might
      be expected to be ineffective due to the enhanced expression of specific
      resistance factors.

PMID- 1349794
TI  - HER-2/neu amplification and overexpression in primary human breast cancer is
      associated with early metastasis.
AB  - The etiology of human breast cancer is poorly understood and no specific marker
      of transformation has been identified. Amplification of HER-2/neu, as reported in
      a comprehensive study by Slamon et al, was found to be the most powerful
      predictor of disease-free and overall survival after the status of the axillary
      lymph nodes. Our study examines the HER-2/neu oncogene in 61 primary human breast
      cancers at both the DNA level (by Southern blotting) and the protein level (by
      immunohistochemical methods). Of the 61 tumors analyzed in our study, 17 (28%)
      had amplification of HER-2/neu. There was no significant correlation of HER-2/neu
      amplification with age, tumor diameter or hormone receptor status; however,
      amplification and overexpression of HER-2/neu was significantly correlated with
      the status of the axillary lymph nodes (P = 0.02). Of 16 patients with
      amplification of HER-2/neu, 14 (88%) had positive regional nodes. One of the two
      node negative cases with amplified HER-2/neu had bone marrow micrometastasis.
      Overall, 16 out of 17 (94%) tumors of the patients having amplified HER-2/neu had
      metastatic disease at the time of diagnosis. In summary, HER-2/neu amplification
      is associated with early tumor dissemination in primary human breast cancer and
      may be a marker of poor prognosis.

PMID- 1349795
TI  - Isolation and characterization of putative intrinsic multidrug resistant Chinese
      hamster ovary cells by fluorescence activated cell sorting.
AB  - Most multidrug resistant cell lines reported in the literature were established
      by long-term continuous exposure of cells to stepwise increasing concentrations
      of antitumor drugs. However, these resistant cell lines may not be relevant to
      the majority of clinically resistant cells. In this study, we described the
      establishment of doxorubicin (Dox)-resistant Chinese hamster ovary cells by
      repeated flow cytometric cell sorting using the intrinsic fluorescence of Dox. In
      each sorting, the 15% least fluorescent cells were fractionated, grown to mass
      culture and sorted again. Results from a total of nine sorting cycles showed that
      the intracellular levels of Dox in the sorted cells were inversely proportional
      to the number of sorting cycles. The levels of P-glycoprotein mRNA in the sorted
      cells were increased, but reached a plateau of 2-3 fold after the fifth sorting
      cycle. The sorted cells exhibited a moderate but stable multidrug-resistant
      phenotype. Because the procedure involved minimal exposure of cells to the drug,
      the isolated cells are most likely related to naturally occurring (intrinsic) MDR
      cells.

PMID- 1349797
TI  - A single 24h contact time with adriamycin provokes the emergence of resistant
      cells expressing the Gp 170 protein.
AB  - We investigate here, in A549 cells, the influence of a single short (1h) or long
      (24h) adriamycin (ADR) contact time on the long-term cytotoxicity of the drug and
      on the emergence of resistant cells. In contrast to a 1 h ADR contact, a 24 h
      treatment provokes the emergence of resistant cells overexpressing the Gp170
      protein and this overexpression is maintained for at least three months without
      any drug selection pressure.

PMID- 1349796
TI  - Further characterization of two distinct adriamycin-resistant sublines from LoVo
      human colon carcinoma cells.
AB  - We previously reported that two multidrug resistant sublines, AdR1.2 and SRA1.2,
      derived from LoVo human colon carcinoma cells, apparently expressed different
      resistance phenotypes including differential expression of p-glycoprotein (Pgp).
      Here, we further examined and compared other potential resistance mechanisms
      between AdR1.2 and SRA1.2 resistant cells. Our results showed that the Pgp
      mediated AdR1.2 cells possessed an activated drug efflux pump and decreased
      nucleus binding of Adriamycin, while the non-Pgp-mediated SRA1.2 cells only held
      the second feature. Verapamil, however, partially reversed resistance in both
      sublines. Although glutathione-s-transferase was overexpressed in AdR1.2 but not
      in SRA1.2, both sublines had lower susceptibilities to drug-induced DNA strand
      breaks and greater capacities to repair such damage than did LoVo cells. These
      data suggest that, despite the differences in multidrug resistance phenotypes,
      the features of decreased susceptibility to DNA damage and enhanced DNA repair
      capacities may represent the common mechanisms responsible for drug resistance in
      both Pgp- and non-Pgp-mediated multidrug resistant cells.

PMID- 1349798
TI  - Anticancer role of dendritic cells (DC) in human and experimental cancers--a
      review.
AB  - The bone marrow-derived dendritic cells (DL/LC) are antigen-presenting accessory
      cells functioning as part of the immune system. In addition, DC/LC in epithelial
      tissues may have the capacity to be involved in cellular interactions which may
      have regulatory functions. Such properties can also be noted when LC/DC interact
      with cancer cells in tumors. The present review summarizes reports which suggest
      that the outcome of a primary tumor in patients depends on the presence or
      absence of DC/LC in the tumor. The evidence showing that the presence of DC/LC in
      primary tumors indicates that a good prognosis may be reached are presented and
      discussed. Based on these observations and the ability of immunomodulators to
      enhance the activity of DC/LC and the ability of these cells to enter into
      tumors, it is suggested that the molecular basis of DC/LC activity against
      primary tumors cells should be investigated. It is possible that activation of
      DC/LC, thereby enhancing their ability to enter primary tumors, and the
      abrogation of the ability of DC/LC-resistant tumors to destroy or prevent DC/LC
      from entering the tumor, could be developed as an effective anti-cancer approach.

PMID- 1349799
TI  - Cell proliferation of transitional cell bladder cancer determined by PCNA/cyclin
      immunostaining. A histopathological description.
AB  - The fraction of proliferating cells in 178 transitional cell carcinomas (TCCs)
      was determined by proliferating cell nuclear antigen (PCNA/cyclin)
      immunostaining. The fraction of positive nuclei ranged between 0% and 100%. In
      WHO grade 1 tumours only occasional cells were positive for PCNA/cyclin, whereas
      nearly all of the nuclei in WHO grade 3 tumours were positive for PCNA/cyclin (p
      less than 0.0001). Nodular tumours showed a higher growth fraction than papillary
      tumours (p less than 0.0001). Superficial Ta-T1 tumours showed a significantly
      lower fraction on nuclei positive for PCNA/cyclin than muscle invasive tumours (p
      less than 0.0001). Tumours with pelvic lymph node metastasis also had a high
      growth fraction (p less than 0.0001). The growth fraction as determined by
      PCNA/cyclin immunostaining was significantly related to aneuploidy (p less than
      0.0001, S phase fraction (p less than 0.0001) and mitotic frequency (p less than
      0.0001). The results show that cell proliferation in the context of
      histopathology can be assessed by PCNA/cyclin immunostaining in TCC. The results
      suggest that PCNA/cyclin immunostaining has prognostic value in TCC and
      consequently is clearly a subject for further studies as a prognostic variable.

PMID- 1349800
TI  - The genetics of multiple endocrine neoplasia syndromes.
AB  - The familial nature of multiple endocrine neoplasia syndromes (FMEN) has been
      recognized for some time but little is known about their cause. Recent
      application of new molecular techniques has mapped FMEN syndromes to specific
      chromosomes and provided evidence for the mechanism through which neoplasia
      occurs. In this review, we describe the techniques that led to recent advances in
      our understanding of FMEN and we discuss the evidence supporting proposed
      molecular mechanisms of neoplasia.

PMID- 1349801
TI  - 23rd Lunteren lectures on molecular genetics protein targeting, transport and
      secretion.

PMID- 1349803
TI  - Expression of a human multidrug resistance gene in human ovarian carcinoma cell
      lines.
AB  - To investigate the possible role of the multidrug resistance phenotype to
      chemoresistance in human ovarian carcinoma, we have analyzed human multidrug
      resistance gene (mdr 1) expression in 8 human ovarian adenocarcinoma cell lines.
      An increase in P-glycoprotein level specific to multidrug-resistant tumor cells
      was not apparently associated with the increase in resistance to vincristine
      (VCR) or doxorubicin (Adriamycin). Mdr 1 transcripts (4.5 kilobases) were
      observed in the RNA preparation obtained from only one cell line (SHIN-3) that
      showed the highest resistance to both drugs in vitro and in vivo. No cell lines
      showed mdr 1 DNA amplification. These results suggest that the insensitivity of
      human ovarian carcinoma to chemotherapy could be partly explained by the
      expression of mdr 1.

PMID- 1349804
TI  - [VIIth Congress (IInd International Congress). New biophysical approaches in
      pediatrics. Marseille, 26 October 1991. Abstracts].

PMID- 1349802
TI  - Biophysical studies of recognition sequences for targeting and folding.

PMID- 1349806
TI  - Cost of beta-adrenergic receptor blocking agents for ocular hypertension.
AB  - We compared the cost per drop and cost per year of therapy for five commercially
      available ocular beta-blockers (Timoptic, Betagan, Betoptic, Betoptic S, and
      Optipranolol) based on retail prices in Philadelphia, Pa; New Orleans, La; and
      San Francisco, Calif. Variations in bottle volumes and drop size combined to
      yield up to a 48% differential in number of drops per bottle. Average retail
      price variations were 28% within brands (between pharmacies), 29% between brands,
      and 29% between regions. Yearly costs were consistently less with larger bottles.
      Factoring drops-per-bottle, cost of brand, and cost by pharmacy, the cost of a
      year's supply of beta-blocker in 5-mL bottles in the least expensive region (New
      Orleans) ranged from $52.25 for Optipranolol to $278.91 for Betagan (534% of the
      price for Optipranolol). The marked differential in yearly cost among
      antiglaucoma medications should perhaps be a factor in the recommendations made
      by physicians and health-care providers.

PMID- 1349807
TI  - Microscopic polyarteritis presenting with chest infections and acute
      appendicitis.
AB  - We describe a 38-year-old male with antineutrophil cytoplasmic auto-antibody
      (ANCA) positive microscopic polyarteritis who presented with recurrent chest
      infections, lung haemorrhage, renal insufficiency and acute appendicitis.
      Appendectomy was followed by resolution of abdominal symptoms and the surgical
      specimen revealed vasculitis of the serosal vessels. A renal biopsy was performed
      because of impaired renal function and this revealed focal necrotising
      glomerulonephritis with absence of immune deposits. Chest infections were treated
      with antibiotics resulting in partial clinical response, but pulmonary symptoms
      relapsed and a complete resolution was achieved only after plasma exchange and
      the administration of cyclophosphamide. Our observation emphasises the protean
      manifestations of microscopic polyarteritis and the relationship between ANCA and
      disease activity.

PMID- 1349805
TI  - Drug-induced lysosomal disorders in laboratory animals: new substances acting on
      lysosomes.
AB  - Several substances with lysosomotropic activity were investigated in
      toxicological studies. AR-L 115 BS (sulmazol, a cardiotonic agent) was tested on
      beagle dogs; HX-CH 44 BS (a beta-blocker) and SX-AB 1316 SE (an antithrombotic
      agent) were tested on rats, and AF-CX 1325 XX (an antiepileptic agent) was tested
      on both rats and beagle dogs. All organ systems were examined morphologically by
      light and/or electron microscopy. When an increase in the number of lysosomes
      occurred this was confirmed by the pigment scheme according to Krutsay (1971) as
      well as by the detection of acid phosphatase and compared with earlier
      histochemical results. At higher dosages, all substances caused very marked
      proliferation of lysosomes in the liver and/or kidneys. HX-CH 44 BS also caused
      such proliferation in striated muscles and in the lungs. A brown discolouration
      of the kidneys was found with sulmazol and AF-CX 1325 XX. This finding
      corresponded to the microscopically detectable occurrence of numerous lipofuscin
      granules. The reticulum cells in the lymph nodes of dogs were also affected by AF
      CX 1325 XX. It is concluded that the proliferation of lysosomes in various organs
      after administration of the above-mentioned substances is due to an excess of
      substance. The increased substance in the body is then stored in the lysosomes.
      With HX-CH 44 BS, lysosomal autodigestion of mitochondria in the skeletal
      musculature and in the alveolar macrophages of the lungs was found. The selective
      lysosomal incorporation of mitochondria has not been described up to now and in
      our opinion, this constitutes a special feature. The results otherwise largely
      correspond to those already described in the literature. Systemic
      phospholipidosis such as occurs with some other substances was not detectable.
      The incorporation of the substance causes several types of lysosomal inclusion.
      Uptake of the substance in lysosomes either leads to overt autodigestion of
      organelles such as mitochondria (HX-CH 44 BS) or peroxisomes or to residual
      lysosomes of dense structure which histochemically resemble lipofuscin. SX-AB
      1316 SE serves as an example of a substance which is stored directly by lysosomes
      in crystalline form. Above all, in the liver the substance is taken up not only
      by the sinusoidal stellate cells but also by hepatocytes.

PMID- 1349809
TI  - [VIth meeting on Research in Cellular Pathology. Paris, December 11, 1991.
      Abstracts].

PMID- 1349808
TI  - Treating children with attention-deficit hyperactivity disorder.

PMID- 1349810
TI  - Acute disseminated encephalomyelitis after Japanese B encephalitis vaccination.
AB  - A 6-year-old girl (Patient 1) and a 5-year-old boy (Patient 2) with acute
      disseminated encephalomyelitis after Japanese B encephalitis vaccination are
      reported. Drowsiness, paresthesias, and gait disturbance were observed at 14 days
      (Patient 1) and 17 days (Patient 2) after the vaccination; however, transient
      impairment of visual acuity was only found in Patient 1. Laboratory examinations
      revealed slow theta waves on electroencephalography and elevated myelin basic
      protein in the cerebrospinal fluid in both patients. The most striking feature on
      magnetic resonance imaging was the combination of white matter lesions and
      abnormal intensity signals of the thalamus. The administration of oral
      prednisolone (2 mg/kg/day) markedly improved the clinical findings and abnormal
      magnetic resonance imaging findings. A similar magnetic resonance imaging finding
      of abnormal intensity of the thalamus with deep white matter lesions has been
      reported in patients with Japanese B encephalitis; therefore, thalamic lesions
      may be related to the naturally occurring encephalitis.

PMID- 1349811
TI  - Animal models for immunodeficiency diseases.
AB  - Immunodeficient animals continue to provide insights into the development and
      function of the immune system. These animals also serve as models for the
      propagation of normal and malignant human cells and as hosts for infectious
      agents, including HIV. New developments in basic and applied research using
      immunodeficient animals were discussed at a recent workshop.

PMID- 1349812
TI  - Inhibition of synthesis of endothelium-derived nitric oxide in conscious dogs.
      Hemodynamic, renal, and hormonal effects.
AB  - The role of endothelium-derived nitric oxide (EDRF/NO) for control of systemic
      and regional vascular resistances and for regulation of neurohumoral systems was
      investigated by studying the effects of the inhibitor of EDRF/NO-synthesis NG
      nitro-L-arginine (L-NNA; 5 mg/kg) in six conscious dogs. L-NNA increased mean
      arterial pressure by an increase in total peripheral resistance, increased renal
      vascular, and total pulmonary resistances and reflexly decreased heart rate and
      cardiac output. Renal plasma flow, urine flow, and urinary sodium excretion were
      reduced, glomerular filtration rate was not affected. These changes were reversed
      by additional treatment with L-arginine (150 mg/kg). Plasma concentrations of
      renin, norepinephrine, vasopressin, and atrial natriuretic peptide were not
      changed by L-NNA. Our conclusions were that basal release of EDRF/NO plays an
      important physiologic role for control of systemic and regional vascular
      resistances, thereby controlling blood pressure, organ blood flow, and function.
      Neurohumoral systems are not affected by the inhibition of EDRF/NO synthesis and
      do not contribute to the observed vasoconstriction.

PMID- 1349813
TI  - Some lessons from systolic hypertension in the elderly program (SHEP).

PMID- 1349814
TI  - Systolic hypertension in the elderly program (SHEP) and Swedish trial in old
      patients with hypertension (STOP). The promises and the potential problems.

PMID- 1349815
TI  - Heart rate changes evoked by hypoxia in the anaesthetized, artificially
      ventilated cat.
AB  - Reflex changes in heart rate evoked by hypoxia were investigated in cats
      anesthetized with chloralose and ventilated by positive pressure during
      administration of vecuronium or gallamine. In five cats receiving vecuronium and
      with aortic pressure stabilized, systemic hypoxia (arterial O2 pressure (Pa, O2)
      34.9 mmHg) reduced heart rate by 55.8 +/- 7.5 beats min-1 (mean +/- S.E.M.).
      After administration of atropine, hypoxia (Pa, O2 32.1 mmHg) increased heart rate
      by 28.2 +/- 3.4 beats min-1. After subsequent bilateral ablation of carotid sinus
      and vagus nerves, hypoxia (Pa, O2 31.9 mmHg) increased heart rate by 7.1 +/- 1.8
      beats min-1. The cardiac accelerator response to hypoxia was further examined in
      groups of cats treated with gallamine and atropine. In four vagotomized cats,
      local perfusion of both carotid sinuses with hypoxic blood (Pa, O2 37.7 mmHg)
      increased heart rate by 15.5 +/- 2.3 beats min-1. In the same cats, systemic
      hypoxia (Pa, O2 38.3 mmHg) increased heart rate by 16.4 +/- 2.3 beats min-1. The
      heart rate increment in cats which had undergone either bilateral adrenalectomy
      or cardiac sympathectomy was similar to the increment in unoperated cats. The
      increment was significantly less in cats which had both adrenal glands and
      cardiac sympathetic nerves ablated. It is concluded that stimulation of the
      carotid bodies in the cat excites both parasympathetic and sympathetic cardiac
      nerves simultaneously.

PMID- 1349816
TI  - Clinical trials referral resource. Clinical trials with all-trans-retinoic acid.

PMID- 1349818
TI  - Plasma concentrations of motilin and somatostatin are increased in late pregnancy
      and postpartum.
AB  - OBJECTIVE: To examine plasma levels of motilin and somatostatin throughout
      pregnancy. DESIGN: Prospective observational study. SETTING: University Hospital,
      Norway. SUBJECTS: Eight healthy pregnant women (aged 24-38 years) six of them
      primigravidae and eight healthy non-pregnant women of similar age with ovulatory
      menstrual cycles. INTERVENTIONS: In the pregnant women blood samples were
      obtained at 4-week intervals from 8 weeks gestation throughout pregnancy and
      again at 5 days and 28 days postpartum. In the non-pregnant controls blood
      samples were obtained on cycle days 4, 7, 10, 13, 14, 15, 18, 21 and 24. MAIN
      OUTCOME MEASURES: Plasma levels of motilin and somatostatin. RESULTS: Plasma
      concentrations of both motilin and somatostatin rose continuously during
      pregnancy, and motilin levels increased still further to a peak of 165.1 (SE
      35.8) pmol/l at 5 days postpartum. Plasma motilin levels were significantly
      higher during the third trimester and at 5 days postpartum compared with non
      pregnant controls (P less than 0.0001). The highest plasma somatostatin levels
      were found at 40 weeks gestation and at 5 days postpartum (mean 32.1 SE 1.1
      pmol/l). Somatostatin levels were significantly higher during the second and
      third trimester and the postpartum period compared with levels in the follicular
      phase of the non-pregnant controls (P less than 0.0001). CONCLUSIONS: Circulating
      levels of motilin cannot play a major role in the relaxation of the gut in
      pregnancy, but somatostatin may play a part in regulating motility.

PMID- 1349817
TI  - Gamma-glutamyltransferase, aspartate and alanine aminotransferases and their
      ratio, mean cell volume and urinary dolichol in pregnant alcohol abusers.
AB  - OBJECTIVE: To study the activities of serum gamma-glutamyltransferase (GGT),
      aspartate and alanine aminotransferases (AST, ALT), and their ratio (AST/ALT),
      mean erythrocyte cell volume (MCV) and urinary dolichol output in alcohol-abusing
      pregnant women, and compare the results to those of abstinent pregnant women.
      DESIGN: Prospective descriptive study. SETTING: Special outpatient clinic for
      pregnant problem-drinkers in the department of Obstetrics and Gynaecology,
      Helsinki University Central Hospital, Finland. SUBJECTS: 25 pregnant women
      referred to the special clinic at between 12 and 24 weeks gestation, they
      consumed at least 150 g of ethanol weekly, and a control group of 20 abstinent
      pregnant women matched for age, parity and smoking habits. INTERVENTIONS: The
      women were encouraged to visit the clinic at 2-4 week intervals. At each visit
      blood and urine samples were obtained, and the women were interviewed on their
      alcohol consumption during the previous weeks and encouraged to abstain in the
      future. MEAN OUTCOME MEASURES: Neonatal condition, fetal alcohol effects (FAE) in
      the newborn. Serum activities of GGT, AST and ALT, the AST/ALT ratio, the MCV,
      and the urinary concentration of dolichol in alcohol-abusing women with either
      healthy or FAE infants, compared with those of abstinent women with healthy
      infants. RESULTS: Of the 25 alcohol-abusing women 13 gave birth to infants with
      FAE and 12 to healthy infants. All the women in the control group gave birth to
      healthy infants. GGT, AST and ALT activities were increased in all alcohol
      abusing women, regardless whether the infant had FAE or not. GGT was the best of
      these markers, GGT activities above the 95th normal centile were found in 33% of
      the samples from all alcohol-abusing women. The AST/ALT ratio, MCV and urinary
      dolichol concentration were poor indicators of abusive drinking. CONCLUSIONS:
      Maternal alcohol abuse is difficult to assess by laboratory tests. Of the
      commonly used and easily available tests, GGT proved to be the best in our study.

PMID- 1349819
TI  - The lipid ballet. Molecular Aspects of Lipid Flow in the Cell, A Jacques Monod
      Conference, sponsored by the Centre National de la Recherche Scientifique,
      Roscoff, France, September 16-20, 1991.

PMID- 1349820
TI  - Initiation and beyond: molecular determinants of gene regulation. Mechanisms of
      Transcription Control, A Jacques Monod Conference, sponsored by the Centre
      National de la Recherche Scientifique, Roscoff, France, September 30-October 4,
      1991.
AB  - The study of the mechanisms of transcriptional control continues to be an
      exciting area of research. The characterization of the constituents of the
      initiation complex and their interactions are leading to a greater understanding
      of gene regulation. The findings presented at this meeting emphasized the need to
      understand these interactions in three-dimensional space to effectively account
      for the observed regulation of the initiation of transcription.

PMID- 1349821
TI  - Glycosyl-phosphatidylinositol: a novel mechanism of signal transduction. Workshop
      on Role of Glycosyl-phosphatidylinositol in Cell Signalling, sponsored by
      Fundacion Juan March, Madrid, Spain October 21-23, 1991.

PMID- 1349822
TI  - What makes a steroid a neurosteroid? Neurosteroids and Brain Function, sponsored
      by the Fidia Research Foundation, New Orleans, LA, USA, November 8-9, 1991.

PMID- 1349824
TI  - Developmental and neurologic correlates of treatment response in schizophrenia.
AB  - Reliable predictors of outcome in schizophrenia remain elusive, and assessment of
      unidimensional variables is unlikely to provide new information. We examined
      developmental, neurologic and psychosocial variables together to assess their
      correlation with several separate aspects of outcome in male schizophrenic
      patients (N = 31) treated with neuroleptics for a minimum of six months. Outcome
      measures evaluating social performance were significantly inter-correlated, but
      these measures did not correlate significantly with "positive" symptom measures.
      Persistent positive symptoms were predicted by post-natal neurologic impairment.
      Persistent negative symptoms and social dysfunction were predicted by
      psychosocial dysfunction during the developmental years. Poor early treatment
      response significantly correlated with persistent positive symptoms and
      psychosocial dysfunction. Impairment on neurobehavioral testing correlated
      significantly with post-natal neurologic impairment and with persistent positive
      symptoms.

PMID- 1349826
TI  - Neurotoxicity related to lithium and neuroleptic combinations? A retrospective
      review.
AB  - The question of toxic interactions resulting from combinations of lithium and
      neuroleptic drugs is largely based on anecdotal reports. We replicated the
      methods of Miller and Menninger (1987) who reported that 27% of manic patients on
      treatment with lithium and neuroleptics developed toxicity. We found no cases of
      neurotoxicity as defined in the earlier report. Pharmacologic mechanisms and
      differences in the clinical findings of the two studies are discussed.

PMID- 1349825
TI  - Cerebrospinal fluid concentrations of neuropeptide Y in depressed patients and in
      controls.
AB  - Concentrations of Neuropeptide Y-like (NPY-LI) immunoreactivity in cerebrospinal
      fluid (CSF) were measured in a group of depressed patients (n = 24) and compared
      with that of control subjects (n = 12). CSF-NPY-LI was significantly reduced in
      the group of non-endogenously depressed patients when classified according to
      Newcastle Rating Scale for Depression--1971 (N-II). No significant correlation
      was found in the control or depressed groups between lumbar concentrations of NPY
      LI and a number of other neurotransmitters.

PMID- 1349823
TI  - The use of carbamazepine in the treatment of schizophrenic and schizoaffective
      psychoses: a review.
AB  - This article reviews current literature on the clinical efficacy of carbamazepine
      (CBZ) administration in schizophrenic and schizoaffective psychoses. With respect
      to the use of CBZ in cases of aggression, overactivity and other behavioral
      dyscontrol syndromes, only a few, mainly open, studies have been conducted.
      Attention to the efficacy of CBZ in schizophrenia and related psychoses was
      rather late in developing, with most of the studies done since 1981. Although the
      results of the different controlled and uncontrolled experiments are very
      difficult to compare, the results generally indicate beneficial effects-
      particularly if CBZ is used as an adjunct to neuroleptic medication. Suggestions
      for future research strategies to maximize the usefulness of CBZ in schizophrenia
      and related disorders are given.

PMID- 1349827
TI  - Neuroleptic malignant syndrome: a preventive program.
AB  - Neuroleptic Malignant Syndrome is a very serious side effect of antipsychotic
      medications. The paper describes a preventative program which was instituted in
      an inpatient unit of a provincial psychiatric hospital. There have been no
      mortalities from Neuroleptic Malignant Syndrome (NMS) during this program. A
      suspicion of NMS by clinical evaluation and laboratory tests resulted in prompt
      management. The recommended management plan is described.

PMID- 1349828
TI  - Sequence and expression of rat ICAM-1.
AB  - We have isolated cDNA clones-coding for rat intercellular adhesion molecule-1
      (RICAM-1) from a cDNA library constructed from rat Ax cells stimulated with IL-1
      beta using the mouse ICAM-1 cDNA as a hybridization probe. The RICAM-1 sequence
      shows 79.1% homology with mouse ICAM-1 and 55.6% homology with human ICAM-1 at
      the nucleic acid level. In order to examine the expression of RICAM-1 on Chinese
      hamster ovary (CHO) cells, we constructed the vector, pSV-RICAM1-neo, containing
      the SV40 promoter. Flowcytometric analysis showed that CHO-K1 cells transfected
      with pSV-RICAM1-neo expressed high amounts of RICAM-1 on their surfaces.

PMID- 1349829
TI  - Positive and negative symptoms in schizophrenia: where are the data?

PMID- 1349830
TI  - Alpha 2-adrenoceptors in the brain of suicide victims: increased receptor density
      associated with major depression.
AB  - To examine directly in the brain the status of the alpha 2-adrenoceptor in major
      depression, the specific binding of the agonists [3H]clonidine and [3H]UK 14304
      was quantitated in various brain regions of suicide victims with a retrospective
      diagnosis of depression or other psychiatric disorders. In depressed suicides,
      the binding capacity of [3H]clonidine was found to be increased in the
      hypothalamus (Bmax 35%-55% greater), and to a lesser extent in the frontal
      cortex, as compared with that in matched controls, schizophrenic suicides, or
      suicides with various diagnosis. The binding capacity of [3H]UK 14304 also was
      found increased in the frontal cortex (Bmax 30% greater), and to a lesser extent
      in the hypothalamus, of depressed suicides. In other brain regions such as the
      amygdala, hippocampus, and cerebellum there also was a tendency for an increased
      receptor density associated with suicide. Moreover, in the frontal cortex of
      suicides, the potency of norepinephrine in displacing the binding of the
      antagonist [3H]idazoxan also was found increased (Ki decreased eight-fold). The
      results indicate that the density and affinity of alpha 2A-adrenoceptors in the
      high-affinity state are increased in the brain of depressed suicides.

PMID- 1349831
TI  - Neuroleptic dysphoria: so what's new?

PMID- 1349832
TI  - Pleurothotonus and the Pisa syndrome.

PMID- 1349833
TI  - Paranoid schizophrenia may be caused by dopamine hyperactivity of CA1
      hippocampus.
AB  - Explicit consolidation of memory, or fixation of declarative belief, appears to
      be physically represented in changes of synaptic conductances of neurons in the
      parietal-temporal-occipital association cortex (PTO) of the mammalian forebrain.
      This fixation of belief in PTO is postulated to be critically dependent on a
      diffuse reinforcement signal via the inferior temporal cortex (ITC) ultimately
      caused by an increased output of the CA1 pyramidal cells of hippocampus.
      Analogous to the reinforcing mechanisms of other forebrain systems, this updating
      of the connection weights of the neural nets in PTO by the output of the critical
      neurons in CA1 is directly related to concentrations of dopamine (DA). We propose
      that the delusions (i.e., unreasonable beliefs) of paranoid schizophrenia are
      caused by a hyperactivity of the same DA-sensitive CA1 neurons that are
      responsible for the fixation of normal beliefs. The dramatic reduction in
      delusions with administration of neuroleptics, as DA D2 blockers, in
      schizophrenics may thus be explained by their acting to ameliorate the
      hyperactivity of these CA1 DA D2 receptors.

PMID- 1349834
TI  - [Are beta-2 agonists necessary in the treatment of bronchial asthma in its stable
      phase?].

PMID- 1349835
TI  - Synthesis and neurotoxicological evaluation of putative metabolites of the
      serotonergic neurotoxin 2-(methylamino)-1-[3,4-(methylenedioxy)phenyl] propane
      [(methylenedioxy)methamphetamine].
AB  - Theoretical considerations and recent experimental data have prompted an
      investigation of the neurotoxicological properties of the 6-hydroxydopamine
      analogue 2-(methylamino)-1-(2,4,5-trihydroxyphenyl)propane (5) and its possible
      precursor 1-[2-hydroxy-4,5-(methylenedioxy)phenyl]-2- (methylamino)propane (4),
      potential metabolites of the serotonergic neurotoxin MDMA. Systemic,
      intracerebroventricular, and intraparenchymal (intrastriatal and intracortical)
      administration of 4 led to no detectable alterations of hippocampal or cortical
      serotonin or striatal dopamine levels in the rat under conditions that caused
      significant biogenic amine depletions by established neurotoxins. By contrast,
      intraparenchymal administration of 5 caused profound depletions of dopamine and
      serotonin, with the former being more severely depleted than the latter. Although
      not conclusive, these data suggest a possible role for 5 in the mediation of
      MDMA's neurotoxic actions.

PMID- 1349836
TI  - A new homeobox-leucine zipper gene from Arabidopsis thaliana.
AB  - We have isolated a homeobox-containing gene from Arabidopsis thaliana using a
      degenerate oligonucleotide probe corresponding to the most conserved region of
      the homeodomain. This strategy has been used previously to isolate homeobox
      containing genes from Caenorhabditis, and recently from A. thaliana. The
      Arabidopsis genes have an unusual structure in that they have a leucine zipper
      motif adjacent to the carboxy terminal region of the homeo domain, a feature not
      found in homeobox-containing genes isolated from animals. We report the isolation
      and primary structure of a new member of this Arabidopsis homeobox-leucine zipper
      gene family. This new member has the homeodomain and leucine-zipper motif similar
      to the two genes previously identified, but differs from these genes in the part
      corresponding to the carboxy terminus of the polypeptide, as well as in size and
      isoelectric point of the protein.

PMID- 1349838
TI  - Detection of a single base substitution of the gene for prothrombin Tokushima.
      The application of PCR-SSCP for the genetic and molecular analysis of
      dysprothrombinemia.
AB  - The genetic and molecular basis of a mutant prothrombin of 'prothrombin
      Tokushima' was studied by polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) and PCR-restriction fragment length polymorphism (PCR
      RFLP) analyses. The abnormal gene was detected by altered migration by PCR-SSCP
      and by the loss of an MspI site by PCR-RFLP. The gene for prothrombin Tokushima
      was shown to be inherited from the mother of the proband. Sequencing analysis
      using PCR-amplified genomic DNA clarified a substitution of thymine (T) for
      cytosine (C) at position 9,490, changing arginine (Arg) to tryptophan (Trp) at
      position 418 of the polypeptide chain. This point mutation is assumed to be the
      molecular basis of prothrombin Tokushima, firstly, because of the absence of
      distinct changes in Southern blot analysis of the proband's DNA (using a full
      length human prothrombin cDNA as a probe), secondly, because it has the same
      molecular weight as the abnormal gene product, and, thirdly, because of the
      absence of other amino acid abnormalities in the proteolytic peptide-fragments.
      It is concluded that PCR-SSCP and PCR-RFLP were useful for detecting the abnormal
      gene and for directly diagnosing the carrier status of dysprothrombinemia. This
      is the first report of gene analysis of dysprothrombinemia.

PMID- 1349837
TI  - cDNA clones encoding Arabidopsis thaliana and Zea mays mitochondrial chaperonin
      HSP60 and gene expression during seed germination and heat shock.
AB  - Mitochondria contain a nuclear-encoded heat shock protein, HSP60, which functions
      as a chaperonin in the post-translational assembly of multimeric proteins encoded
      by both nuclear and mitochondrial genes. We have isolated and sequenced full
      length complementary DNAs coding for this mitochondrial chaperonin in Arabidopsis
      thaliana and Zea mays. Southern-blot analysis indicates the presence of a single
      hsp60 gene in the genome of A. thaliana. There is a high degree of homology at
      the predicted amino acid levels (43 to 60%) between plant HSP60s and their
      homologues in prokaryotes and other eukaryotes which indicates that these
      proteins must have similar evolutionarily conserved functions in all organisms.
      Northern- and western-blot analyses indicate that the expression of the hsp60
      gene is developmentally regulated during seed germination. It is also heat
      inducible. Developmental regulation of the (beta-subunit of F1-ATPase, an enzyme
      complex that is involved in the cyanide-sensitive mitochondrial electron
      transport system, indicates that imbibed embryos undergo rapid mitochondrial
      biogenesis through the early stages of germination. Based on the functional role
      of HSP60 in macromolecular assembly, these data collectively suggest that the
      presence of higher levels of HSP60 is necessary during active mitochondrial
      biogenesis, when the need for this protein is greatest in assisting the rapid
      assembly of the oligomeric protein structures.

PMID- 1349840
TI  - Why haven't we cured multidrug resistant tumors?

PMID- 1349839
TI  - An in vivo alpha-2 assay reversal of opioid-induced muscular rigidity and
      neuroleptic-induced ptosis.
AB  - A method is described to detect selective alpha-2 adrenergic agonists in vivo.
      Palpebral ptosis is induced in rats by the neuroleptic agent haloperidol (Hal),
      or by tetrabenazine (TBZ) methanesulfonate. Twenty minutes later, test compounds
      are injected, and ptosis is scored. In a separate test, muscular rigidity is
      induced by the opioid, fentanyl, and subsequently, test compounds are assessed
      for their ability to reverse muscular rigidity. Results indicate that only alpha
      2 agonists reliably reverse neuroleptic-induced and TBZ-induced ptosis, as well
      as opioid-induced rigidity. An alpha-1 antagonist reversed only rigidity,
      whereas, alpha-2 antagonists and beta-agonists were generally ineffective in all
      tests. Therefore, the ability to reverse neuroleptic and TBZ-induced ptosis along
      with the ability to reverse opioid-induced muscular rigidity is a characteristic
      unique to alpha-2 agonists.

PMID- 1349841
TI  - A reliable method for the use of oligonucleotides as probes in blot-hybridization
      experiments.
AB  - We have developed a ligation and specific-primer radiolabeling method that allows
      the use of oligonucleotides as probes in blot-hybridization experiments. The
      major advantage of the protocol is that standard hybridization and washing
      conditions may be used and yield high signals and low background. The observed
      increase in the stability and intensity of the hybridization signals appears to
      result from both increased length and specific radioactivity of the hybridization
      probe.

PMID- 1349843
TI  - Neurophysiologic basis of acupuncture.
AB  - Research has shown that the benefits of acupuncture are truth, not fiction.
      Acupuncture effects are due to local effects, stimulation of neuroendocrine
      systems, and modulation of the body's electromagnetic energy. The exact
      mechanisms activated depend on point selection, type of stimulation, and probably
      time of day. The effectiveness of the treatment will depend on the disease entity
      treated and the skill and knowledge of the acupuncturist. Knowledge should
      include both the fundamental principles of Chinese medicine and the more recent
      scientific understanding of acupuncture's physiologic basis.

PMID- 1349842
TI  - Mapping of ornithine aminotransferase gene sequences to mouse chromosomes 7, X,
      and 3.
AB  - Ornithine aminotransferase (OAT), a mitochondrial matrix enzyme, is deficient in
      patients with gyrate atrophy of the choroid and retina. In human, the OAT
      structural gene maps to Chromosome (Chr) 10q26 and several OAT-related sequences,
      some of which are known to be processed pseudogenes, which map to Xp11.3-11.21.
      Here, we report chromosomal localization in the mouse of the OAT gene and related
      sequences. Genomic DNA blot analysis of a well-characterized panel of Chinese
      hamster x mouse somatic cell hybrids using a human OAT probe revealed two murine
      loci, one on mouse Chr 7 and the other on Chr X. In addition, segregation of
      restriction fragment length polymorphisms (RFLPs) detected by the OAT probe in
      recombinant inbred (RI) strains detected a third locus on Chr 3 and positioned
      the X locus near Cf-8 and Rsvp. Progeny of an intersubspecific backcross were
      used to map the Chr 7 locus between Tyr and Int-2, near Cyp2e-1.

PMID- 1349844
TI  - [New developments in drug therapy of glaucoma].

PMID- 1349845
TI  - Treatment of hypertension in older adults.

PMID- 1349846
TI  - Fatal neutropenic enterocolitis associated with sulphasalazine therapy for
      rheumatoid arthritis.
AB  - Neutropenia is a recognized complication of sulphasalazine therapy in patients
      with rheumatoid arthritis. It is usually mild, transient and rarely associated
      with serious sequelae. We describe a patient with rheumatoid arthritis who
      developed fatal neutropenic enterocolitis complicated by tracheo-oesophageal
      fistula following treatment with sulphasalazine.

PMID- 1349847
TI  - Pulsed dye laser lithotripsy--the Toa Payoh Hospital experience.
AB  - We report our experience with pulsed dye laser lithotripsy in the treatment of
      100 ureteric stones in 95 patients over a 14-month period from July 1989 to
      September 1990. The overall rate of successful stone fragmentation was 97%. There
      was a low incidence of minor complications--mild haematuria, ureteric colic and
      urinary tract infection; ureteric perforation occurred in only 3 patients, all of
      whom were successfully treated conservatively. Pulsed dye laser lithotripsy is a
      safe and effective mode of treatment for ureteric stones. Current indications for
      laser fragmentation of stones are ureteric stones, impacted pelviureteric
      junction stones and Steinstrasse.

PMID- 1349848
TI  - Eurosurgery 1992. Second European Congress of Surgery. Brussels, June 2-5 1992.
      Abstracts.

PMID- 1349849
TI  - Therapy of an animal model of human gastric cancer using a combination of anti
      erbB-2 monoclonal antibodies.
AB  - Amplification and/or overexpression of the erbB-2 gene have been demonstrated in
      20-30% of adenocarcinomas of the breast, ovary, lung, and stomach and are
      associated with aggressive clinical course and poor prognosis. Interference with
      erbB-2 function by the use of monoclonal antibodies is a promising approach to
      the treatment of these diseases. In this study we demonstrate that a combination
      of two anti-erbB-2-specific antibodies inhibited the growth of human gastric
      tumor cells in vitro. This combination antibody therapy also inhibited the growth
      of human tumor cell lines growing as xenografts in nude mice and was able to
      dramatically reduce established tumors. This is the first reported observation of
      tumor regression induced by anti-erbB-2 monoclonal antibodies. Treatment was not
      curative in that tumors regrew after 6 weeks. Treatment with either single
      antibody alone did not inhibit cell growth or tumor formation. Pulse chase and
      tyrosine kinase activity experiments were used to investigate the activity of the
      erbB-2 gene product (gp185erbB-2). The formation of complexes by two antibodies
      was found to interfere with receptor function and mimic some properties of a
      typical receptor ligand. Selective interference of the erbB-2 receptor by
      combination antibody therapy may be advantageous for the treatment of human
      cancers.

PMID- 1349850
TI  - p53 mutations are associated with 17p allelic loss in grade II and grade III
      astrocytoma.
AB  - Loss of genetic material on the short arm of chromosome 17 is observed in
      approximately 40% of human astrocytomas (WHO grades II and III) and in
      approximately 30% of cases of glioblastoma multiforme (WHO grade IV). Previous
      studies of glioblastoma multiforme have shown that the p53 gene, located on the
      short arm of chromosome 17, is frequently mutated in these glioblastomas. To
      explore whether lower-grade astrocytomas are also associated with corresponding
      mutations of the p53 gene, we have investigated a series of 22 human astrocytomas
      of WHO grades II and III both for loss of heterozygosity on chromosome 17p and
      for p53 mutations. Mutations in the conserved regions of the p53 gene were
      identified by single strand conformation polymorphism analysis of exons 5, 6, 7,
      and 8 and were verified by direct DNA sequencing of the polymerase chain reaction
      products. p53 mutations were observed in 3 of 8 grade II astrocytomas and 4 of 14
      grade II astrocytomas. In all 22 tumors, allelic loss of the short arm of
      chromosome 17 was investigated by restriction fragment length polymorphism
      analysis. One-half of the grade II astrocytomas (4 of 8) and grade III
      astrocytomas (7 of 14) exhibited allelic loss on chromosome 17p. Mutations in the
      p53 gene were exclusively observed in tumors with allelic loss on 17p. Our
      results show that p53 mutations are not restricted to glioblastoma multiforme and
      may be important in the tumorigenesis of lower-grade astrocytomas and that p53
      mutations in lower-grade astrocytomas are associated with loss of chromosome 17p.
      These findings are consistent with a recessive mechanism of action of p53 in WHO
      grade II and III astrocytoma tumorigenesis.

PMID- 1349851
TI  - [Study on natural infection, biting and transovarial transmission of epidemic
      haemorrhagic fever virus in Leptotrombidium (L.) scutellare].
AB  - In order to clarify the significance of Leptotrombidium (L.) scutellare in
      transmitting EHF, from Oct. to Nov. 1988, lungs of rodents captured in endemic
      areas of EHF in Shangxi Province were taken for detecting EHF antigen by IFAT,
      Twenty-six out of 459 lungs were positive (5.7%). Six strains of EHFV were
      isolated from L. (L.) scutellare collected from the rodents. In Oct. 1989, 28
      Apodemus captured from areas without reported cases of EHF were placed on
      grassland in endemic areas, free L. (L.) scutellare were lured in all mice and 3
      strains of EHFV were isolated. The above results demonstrate that L. (L.)
      scutellare can naturally be infected by EHFV and can be transmitted via bites. It
      is also suggested that this species of mites could transmit the disease
      transovarially. These results further indicate that L. (L.) scutellare can serve
      as a transmitting vector of EHF.

PMID- 1349852
TI  - Three-dimensional structure of the beta subunit of E. coli DNA polymerase III
      holoenzyme: a sliding DNA clamp.
AB  - The crystal structure of the beta subunit (processivity factor) of DNA polymerase
      III holoenzyme has been determined at 2.5 A resolution. A dimer of the beta
      subunit (M(r) = 2 x 40.6 kd, 2 x 366 amino acid residues) forms a ring-shaped
      structure lined by 12 alpha helices that can encircle duplex DNA. The structure
      is highly symmetrical, with each monomer containing three domains of identical
      topology. The charge distribution and orientation of the helices indicate that
      the molecule functions by forming a tight clamp that can slide on DNA, as shown
      biochemically. A potential structural relationship is suggested between the beta
      subunit and proliferating cell nuclear antigen (PCNA, the eukaryotic polymerase
      delta [and epsilon] processivity factor), and the gene 45 protein of the
      bacteriophage T4 DNA polymerase.

PMID- 1349853
TI  - Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain
      and an immunoglobulin homology unit.
AB  - We recently reported that a 44 kd glycoprotein secreted by transformed
      fibroblasts stimulates tyrosine phosphorylation of the product of the neu proto
      oncogene and induces differentiation of mammary tumor cells to milk-producing,
      growth-arrested cells. A partial amino acid sequence of the protein, termed Neu
      differentiation factor (NDF), enabled cloning of the corresponding complementary
      DNA. The deduced structure of the precursor of NDF indicated that it is a
      transmembrane protein whose extracellular portion contains an EGF-like domain
      that probably functions as a receptor recognition site. In addition, the
      ectodomain contains one immunoglobulin homology unit. Despite the lack of a
      recognizable hydrophobic signal peptide at the N-terminus, a recombinant NDF,
      like the natural molecule, is released into the medium of transfected COS-7 cells
      in a biologically active form. Northern blot analysis indicated the existence of
      several NDF transcripts, the major ones being 1.8, 2.6, and 6.7 kb in size.
      Transformation by the ras oncogene dramatically elevated the expression of NDF in
      fibroblasts.

PMID- 1349854
TI  - Association between hepatitis C virus and polyarteritis nodosa.

PMID- 1349855
TI  - Doxazosin: a new alpha 1-adrenergic antagonist.
AB  - The physicochemical properties, pharmacology, pharmacokinetics, cardiovascular
      and metabolic effects, adverse effects, dosage, and administration of doxazosin
      are described, and comparative clinical studies of doxazosin therapy in patients
      with mild to moderate hypertension are reviewed. Doxazosin mesylate, an alpha 1
      adrenoceptor antagonist, is rapidly absorbed after oral administration and
      undergoes extensive hepatic metabolism. The drug decreases blood pressure by
      reducing peripheral resistance. Maximum hypotensive effects occur four to eight
      hours after the dose. Doxazosin favorably affects serum lipids by increasing
      concentrations of high-density lipoprotein (HDL) cholesterol, increasing the
      HDL:total cholesterol ratio, and decreasing concentrations of low-density
      lipoprotein cholesterol, total cholesterol, and triglycerides. In comparative
      clinical trials, doxazosin lowered standing and supine systolic and diastolic
      blood pressures as effectively as other alpha-adrenoceptor antagonists, beta
      adrenoceptor antagonists, diuretics, angiotensin-converting-enzyme inhibitors,
      and calcium-channel-blocking agents. The most frequently reported adverse effects
      are dizziness, headache, nausea, lethargy, and fatigue. Doxazosin may be used
      either alone or in combination with a beta-adrenoceptor inhibitor or a diuretic.
      Orthostatic hypotension after the first dose occurs infrequently and may be
      minimized by initiating therapy at a dosage of 1 mg/day. The dosage may be
      increased at two-week intervals as needed, and blood pressure should be closely
      monitored. Doxazosin has blood-pressure-lowering effects comparable to those of
      other alpha 1-adrenoceptor inhibitors and to those of antihypertensives in other
      drug classes.

PMID- 1349856
TI  - Criteria for use of pancuronium bromide, vecuronium bromide, atracurium besylate,
      tubocurarine chloride, metocurine iodide, pipecuronium bromide, and doxacurium
      chloride in adults.

PMID- 1349857
TI  - Species specificity and developmental patterns of expression of the beta amyloid
      precursor protein (APP) gene in brain, liver and choroid plexus in birds.
AB  - 1. Human APP cDNA hybridized to a 3.5 kb mRNA in liver and brain RNA from
      chickens, pigeons, quail and ducks as well as in RNA from choroid plexus of
      chicken and quail. In contrast to all other species hitherto examined a 1.6 kb
      mRNA hybridizing to APP cDNA was found in abundant amounts in RNA from chicken
      and quail livers. 2. In the chicken, before hatching, the levels of APP mRNA in
      total RNA from liver and choroid plexus were higher than those in RNA from liver
      and choroid plexus of adults. However, RNA from the rest of the brain of chicken
      embryos contained less APP mRNA than RNA from brain of adults. 3. In the chicken,
      between 10 and 40 days after hatching, APP mRNA levels in RNA from liver were
      higher than adult levels, APP mRNA levels in RNA from choroid plexus were similar
      to adult levels and APP mRNA levels in RNA from the rest of brain were below the
      adult levels.

PMID- 1349858
TI  - Linkage map of eight human chromosome 11q markers, including DRD2, spanning 60
      cM.
AB  - We have constructed a linkage map of eight RFLP markers located on chromosome 11q
      in the region of the dopamine D2 receptor gene (DRD2) recognized by probe hD2G1.
      Abnormalities in dopaminergic neurotransmission mediated by this receptor have
      been implicated in several psychiatric disorders. The map was generated using six
      large reference families (from 294 to 419 individuals per locus), which are
      largely independent of the CEPH families, primarily using the LINKMAP and ILINK
      programs of the LINKAGE package of Lathrop and Lalouel. The most likely order and
      recombination frequencies are: [sequence: see text] The relative order of D11S84
      STMY, DRD2-D11S29, and D11S146-INT2 could not be resolved reliably. There were no
      significant sex differences in recombination frequency. We introduce here a
      version of LINKMAP adapted to run under distributed parallel processing (LINDA
      LINKMAP). Using pairwise analyses, we have also placed D11S421 proximal to this
      group.

PMID- 1349859
TI  - Unusual distribution of Zfy and Zfx sequences on the sex chromosomes of the wood
      lemming, a species exhibiting XY sex reversal.
AB  - Sex reversal occurs naturally in the wood lemming (Myopus schisticolor) due to
      the presence in populations of this species of a variant (mutated) X chromosome,
      designated X*. Thus, X*Y animals develop into females, whereas XY animals develop
      into normal males. Chromosome mapping by in situ hybridization of DNA sequences
      homologous to the human ZFY gene localized the wood lemming Zfx sequences to
      region p12----p11 on both the wild-type X and the mutated X* chromosomes, at or
      proximal to a presumed breakpoint (Xp12) involved in the generation of the X*
      chromosome from the normal X, and Zfy sequences along the entire short arm of the
      Y chromosome. Differences between Zfx and Zfx* were readily detected by Southern
      blot analysis. However, both the Zfx and Zfx* genes expressed similarly sized
      transcripts in all adult somatic tissues investigated. Although the precise
      molecular difference between the Zfx and Zfx* genes is still unknown, their
      chromosomal location suggests that either Zfx or some other closely linked
      gene(s) on the X chromosome may be a major X-linked sex-determining gene, Tdx,
      which in the X* chromosome fails to interact properly with the Y-linked testis
      determining gene, Tdy, thus causing X*Y embryos to develop into females. At least
      15 copies of wood lemming Zfy sequences are distributed along the short arm of
      the Y chromosome. Northern hybridization analyses of adult tissues and somatic
      cell lines indicated that these Zfy repeats were transcriptionally inactive.
      Normally, 3-kb Zfy (ZFY) transcripts are readily detected in mouse and human
      testes, especially in the germ cells. It has therefore been postulated that
      expression of the Zfy (ZFY) gene may be important for spermatogenesis. Whether
      the lack of sufficient Zfy transcripts in the testis of the adult wood lemming
      has any impact on spermatogenesis in this species is still to be elucidated by
      further studies.

PMID- 1349860
TI  - Analysis of sex-chromosome aneuploidy in interspecific backcross progeny between
      the laboratory mouse strain C57BL/6 and Mus spretus.
AB  - Sex-chromosomal aneuploidy was identified in four female progeny of 200
      interspecific backcrosses between laboratory mice (C57BL/6Ros) and Mus spretus.
      The progeny included two 39,XO monosomy mice resulting from a backcross with M.
      spretus, as well as a 41,XXX trisomic mouse and a 40,XX/41,XXX mosaic mouse
      resulting from two separate backcrosses with C57BL/6 mice. The parental origin
      and meiotic stage of the aneuploidies was determined for each of the mice using a
      series of markers that identified allelic differences in the parental X
      chromosome genes present in the hybrid female. Two of the probes identified
      differences in repeated elements between the M. spretus and laboratory mouse X
      chromosomes, whereas the remaining sites involved restriction fragment length
      differences of single-copy genes detectable by Southern analysis. These markers
      indicated that the aneuploidies were most likely of maternal origin and that the
      trisomy resulted from a nondisjunction at the second meiotic division. In
      contrast, the mosaic female could have originated either from a trisomic embryo
      that had lost a single X in a portion of its cells or from a mitotic
      nondisjunction during early embryogenesis that resulted in XXX and XO daughter
      cells, with subsequent loss of the XO cells.

PMID- 1349861
TI  - Stimulant effects of 3,4-methylenedioxymethamphetamine in the nucleus accumbens
      of rat.
AB  - This study examined the behavioral effects in rats of intracerebral
      administration of S(+)-3,4-methylenedioxymethamphetamine (S-MDMA) using an
      automated holeboard and open-field apparatus. Administration of S-MDMA into the
      nucleus accumbens septi produced locomotor hyperactivity. Although the stimulant
      effects of S-MDMA administered systemically are antagonized by fluoxetine
      pretreatment, the activating effects of S-MDMA administered into the nucleus
      accumbens were not antagonized by fluoxetine. A similar increase in locomotor
      activity was observed after S-amphetamine administration into the nucleus
      accumbens. In contrast, the selective 5-HT-releasing drug and S-MDMA congener N
      methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB) produces MDMA-like locomotor
      hyperactivity when administered systemically but did not alter locomotor activity
      when injected into the nucleus accumbens. These data indicate that S-MDMA actions
      in the nucleus accumbens are pharmacologically distinct from the primary effects
      of systemically administered S-MDMA. Behavioral effects of S-MDMA in the nucleus
      accumbens may result from the catecholamine-releasing properties that S-MDMA
      shares with S-amphetamine and not via the 5-HT-releasing properties that it
      shares with MBDB.

PMID- 1349862
TI  - Production of endogenous nitric oxide and activation of soluble guanylate cyclase
      are required for N-methyl-D-aspartate-produced facilitation of the nociceptive
      tail-flick reflex.
AB  - The intrathecal (i.t.) administration of either N-methyl-D-aspartate (NMDA, 10
      fmol to 10 pmol) or L-arginine (1 pmol to 10 nmol), but not D-arginine (1 pmol to
      10 nmol), produced a rapid, transient, dose-dependent facilitation (maximal
      response of 30.9 +/- 6.0% and 33.7 +/- 1.5%, respectively) of the nociceptive
      tail-flick reflex (ED50 = 47.8 +/- 15.4 fmol and 11.4 +/- 2.7 pmol,
      respectively). Maximal NMDA-produced facilitation of the tail-flick reflex (1
      pmol i.t.) was completely abolished by prior treatment (10 min prior) with either
      N omega-nitro-L-arginine methyl ester (L-NAME, 10 nmol i.t.), methylene blue (10
      nmol i.t.) or DL-5-aminophosphonovaleric acid (AP5, 100 pmol i.t.). NMDA-produced
      facilitation was completely recovered 40 min after L-NAME, 50 min after methylene
      blue and 30 min after AP5. L-NAME, methylene blue or AP5 did not significantly
      alter baseline tail-flick latency. These results suggest that NMDA-produced
      facilitation of a thermal nociceptive reflex is mediated through activation of an
      NMDA receptor that results in an increase in endogenous nitric oxide and
      activation of soluble guanylate cyclase in lumbar spinal cord.

PMID- 1349863
TI  - Dynorphin-degrading cysteine protease is highly specific for paired arginine
      residues.
AB  - The cleavage of dynorphin and three analogs containing paired basic residues by
      several proteases was investigated. The cysteine protease of neuroblastoma cells
      cleaved only the bond between Arg-Arg residues. Submandibular arginyl
      endopeptidase, however, cleaved bonds between both Arg-Arg and Arg-Lys residues,
      and pancreatic trypsin at the carboxyl sides of both arginine and lysine
      residues. This shows that the cysteine protease is highly specific for paired
      arginine residues.

PMID- 1349864
TI  - Effect of retinoic acid on liver transglutaminase activity and carbon
      tetrachloride-induced liver damage in mice.
AB  - Transglutaminase (TGase) activity in the cytosol fraction of the mouse liver
      increased following intraperitoneal injection of retinoic acid. Retinoic acid
      inhibited the carbon tetrachloride-induced increase in serum alanine transaminase
      activity. These findings suggest that TGase is involved in the effect of retinoic
      acid on carbon tetrachloride-induced liver damage.

PMID- 1349865
TI  - The influence of chronic nicotine treatment on stress-induced gastric ulceration
      and emptying rate in rats.
AB  - Ten-day treatment with nicotine (5, 25 or 50 micrograms/ml drinking water) dose
      dependently intensified gastric ulceration induced by cold-restraint, and
      emptying rate. Stomach contractions produced by graded doses of bethanechol i.v.
      were elevated further by nicotine treatment. It is suggested that chronic
      nicotine administration produces hypersensitivity of the gastric muscarinic
      receptors; stomach hypermotility contributes to the ulcer-worsening action of the
      alkaloid.

PMID- 1349867
TI  - [Natriuretic peptide family].
AB  - The natriuretic peptide system consists of at least three endogenous ligands:
      atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type
      natriuretic peptide (CNP), and three receptors, ANP-A receptor (guanylate cyclase
      A), ANP-B receptor (guanylate cyclase B) and clearance receptor (C receptor).
      ANP, the prototype of natriuretic peptides, is mainly produced in the atrium and
      secreted into the circulation as a cardiac hormone. ANP is also produced in the
      ventricle and in the central nervous system. BNP, first isolated from the porcine
      brain, has a marked divergence in its molecular size and sequence among species.
      In humans and rats, the major site of production of BNP is the ventricle of the
      heart. BNP is also secreted into the circulation as a cardiac hormone. The plasma
      BNP level in normal subjects is approximately one sixths of the plasma ANP level;
      however, the plasma BNP level markedly increases in heart failure, renal failure
      and hypertension and the augmentation of the BNP secretion is much larger than
      that of the ANP secretion. In addition, clearance of BNP from the circulation is
      slower than that of ANP. Furthermore, BNP is secreted more urgently than ANP in
      acute heart failure. CNP distributes mainly in the central nervous system and
      pituitary gland. No significant amount of CNP is detectable in the heart and
      plasma. Thus, CNP is a local regulator rather than a cardiac hormone. Three
      natriuretic receptors have ligand selectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349866
TI  - CD11b-bearing mononuclear leucocytes and IgA levels in the staging of human
      immunodeficiency virus infection.
AB  - Certain immunological parameters (i.e. low CD4+ T cell numbers, high serum
      soluble CD8) have been described as prognostic factors for the progression of
      human immunodeficiency virus (HIV) infection to later clinical stages. In the
      present study we have found in one hundred HIV-infected Spanish patients (81%
      drug abusers, 7% homosexuals, 6% heterosexuals, and 6% other or unknown risk
      groups) that CD11b+ peripheral blood mononuclear cells are increased in those
      with persistent lymphadenopathy as compared to other clinical stages
      (asymptomatic, AIDS-related complex and AIDS). Serum IgA was significantly
      increased in AIDS patients, and in patients at any other clinical stage who had
      concomitant infections (mainly mycobacterial and fungal). CD11b (an integrin with
      complement receptor functions) may thus be of clinical interest for the staging
      of HIV-infected patients, and reflect stage-selective immunological changes in
      mononuclear cell biology during HIV infection. High IgA on the other hand, would
      be a marker of concomitant infection as well as of disease progression. The
      results concern mostly drug addicts (the main risk group in Spain), but may apply
      to the other risk groups because no significant differences were detected between
      drug addicts (n = 81) and non-drug addicts (n = 19) for the studied variables (p
      greater than 0.05).

PMID- 1349868
TI  - Purification and properties of factor XIII from human placenta.
AB  - 1. FXIII was isolated and purified over 4000 fold from human placenta to apparent
      electrophoretic homogeneity by a new procedure including ethanol precipitation.
      DEAE-Cellulose, molecular sieving on Sephacryl S-300 and Phenyl-Sepharose
      chromatography. 2. Its pI was about 5.1. Under appropriate conditions, the
      incubation of FXIII in the presence of thrombin did not lead to inactivation cut
      in the polypeptidic chain. 3. FXIII was also activated by CaCl2 and, in a lesser
      extent, by other divalent cations like SrCl2, BaCl2 or MgCl2. 4. The binding of
      calcium to FXIII exhibited a negative cooperativity. 5. The activity-pH curve of
      the calcium-activated enzyme did not appear very different from that of the
      thrombin-activated enzyme.

PMID- 1349869
TI  - [Orthotopic liver transplantation for metastases of bronchial carcinoid tumor].
AB  - We report the case of a 42 year old man in whom orthotopic liver transplantation
      was performed successfully for unresectable hepatic metastases of a bronchial
      carcinoid tumor. Prior to transplantation, somatostatin therapy, pulmonary
      lobectomy, and systemic chemotherapy (streptozotocin and fluorouracil) were
      performed. After 9 months there were no signs of clinical or biological
      recurrence. Orthotopic liver transplantation might be indicated for unresectable
      and limited liver metastases of neuroendocrine tumor.

PMID- 1349870
TI  - Molecular genetics of the Drosophila melanogaster ovo locus, a gene required for
      sex determination of germline cells.
AB  - The Drosophila melanogaster ovo gene is required for survival and differentiation
      of female germline cells, apparently playing a role in germline sex
      determination. We recovered 60 kb of genomic DNA from its genetic location at
      4E1,2 on the X chromosome. A transcription unit coding for an apparently female
      specific germline-dependent 5-kb poly(A)+ RNA size class is located substantially
      in a 7-kb region, within which three DNA-detectable lesions for mutations that
      inactivate the ovo function are located at two sites approximately 4 kb apart.
      The breakpoint of a deficiency that removes the neighboring lethal
      complementation group shavenbaby (svb) but leaves the ovo function intact maps
      approximately 5 kb to the molecular left of the leftmost ovo mutant site. A class
      of mutations that inactivates both the svb function and the ovo function affects
      genomic DNA between the two ovo sites. Sequences required for the two genetic
      functions are partly overlapping. In spite of this overlap, P element-mediated
      gene transfer of a 10-kb genomic DNA segment containing the 5-kb poly(A)+ RNA
      transcription unit rescues the female sterility phenotypes of ovo mutations, but
      not the svb lethality.

PMID- 1349871
TI  - Genetic analysis of the additional sex combs locus of Drosophila melanogaster.
AB  - Additional sex combs (Asx) is a member of the Polycomb group of genes, which are
      thought to be required for maintenance of chromatin structure. To better
      understand the function of Asx, we have isolated nine new alleles, each of which
      acts like a gain of function mutation. Asx is required for normal determination
      of segment identity. AsxP1 shows an unusual phenotype in that anterior and
      posterior homeotic transformations are seen in the same individuals, suggesting
      that AsxP1 might upset chromatin structure in a way that makes both activation
      and repression of homeotic genes more difficult. Analysis of embryonic and adult
      phenotypes of Asx alleles suggests that Asx is required zygotically for
      determination of segment number and polarity. The expression pattern of even
      skipped is altered in Asx mutant embryos, suggesting that Asx is required for
      normal expression of this gene. We have transposon-tagged the Asx gene, and can
      thus begin molecular analysis of its function.

PMID- 1349872
TI  - Independence of VNTR alleles defined as fixed bins.
AB  - An analysis is presented of data collected by the Federal Bureau of Investigation
      at six unlinked variable number of tandem repeats (VNTR) loci for the United
      States population. Databases have been constructed of VNTR profiles of
      Caucasians, Blacks and Hispanics from Florida, Texas and California. There was
      very little evidence for correlations between lengths for pairs of VNTR
      fragments, within or between loci. When the fragment lengths were amalgamated
      into discrete bins, there was also little evidence for disequilibrium over all
      genotypes, within or between loci, for the Caucasian database, although some
      disequilibrium was found for the Black and Hispanic databases. No disequilibrium
      was found for the Caucasian or Black databases when tests were confined to
      heterozygous individuals. In cases of global disequilibrium, local tests can be
      applied to specific genotypes. The results suggest that, at the bin level,
      frequencies of VNTR profiles can generally be estimated as the products of the
      frequencies of the constituent elements. This overcomes the problem of estimating
      population frequencies when any particular profile does not exist in the
      database. There is some evidence for different frequencies, at the individual bin
      level, between geographic samples within each of the Caucasian, Black and
      Hispanic databases, and considerable evidence for differences between the three
      databases. These differences are less evident for the frequencies of four-locus
      profiles.

PMID- 1349873
TI  - Human immunodeficiency virus (HIV-1): infectivity transmission, risk behaviours
      and host susceptibility.

PMID- 1349874
TI  - Risk estimation in familial adenomatous polyposis using DNA probes linked to the
      familial adenomatous polyposis gene.
AB  - The familial adenomatous polyposis gene has recently been assigned to the long
      arm of chromosome five through linkage to several 5q DNA probes. These probes can
      now be used to trace inheritance of the disease gene in affected families. In
      this study, DNA samples from 152 members of 10 Australian familial adenomatous
      polyposis families have been examined for restriction fragment length
      polymorphisms detected by DNA probes C11P11, ECB27, and YN5.48. Linkage analysis
      confirmed linkage between the familial adenomatous polyposis gene and each probe
      with a maximum combined LOD score of 2.82 for C11P11, 2.90 for ECB27 and 5.49 for
      YN5.48 all at a recombination fraction of zero. Risk estimates were determined
      for the 51 at risk individuals in these families based on their restriction
      fragment length polymorphism data alone or in addition by including the effect of
      age dependent penetrance. Thirty two of those at risk (63%) could be assigned
      specific high (greater than or equal to 95%) or low (less than or equal to 5%)
      risks of developing familial adenomatous polyposis on the basis of their probe
      results. When the effect of age dependent penetrance was included, 26 (51%) fell
      at the extremes of risk (greater than or equal to 99% or less than or equal to
      1%). Such estimates provide a sound basis for planning sigmoidoscopic screening
      of at risk family members and will thus facilitate surveillance in familial
      adenomatous polyposis families.

PMID- 1349875
TI  - GM and KM allotypes and GM RFLP allogenotypes in Micronesians from Nauru.
AB  - Immunoglobulin allotypes of the GM and KM systems were determined in a sample of
      Micronesian subjects from Nauru. Four GM haplotypes were identified in the
      sample: GM*1,3 23 5, 10,11,13,14, GM*1,17 23' 21, GM*1,3 23' 5,10,11,13,14, and
      GM*1,2,17 23' 21, although the last of these may have been introduced by non
      Micronesian admixture. The frequency of the KM*1 allele is 0.115 +/- 0.033, which
      is slightly lower than reported in Micronesians from the Caroline Islands. RFLPs
      generated by the enzymes Taq I and Pvu II and detected by a Hu gamma 4 probe were
      related to GM phenotypes. The haplotypes GM*1,3 +/- 23 5,10,11,13,14 were
      strongly associated with a Taq I 5.0-kb band. The presence and absence of the
      allotype G2M 23 were marked by a Pvu II 7.0 + 2.0 kb pair and a Pvu II 9.0-kb
      fragment, respectively. GM*1,17 23' 21 was strongly associated with a Pvu II 5.0
      + 2.7 kb pair. The different relationships between GM haplotypes and Hu gamma 4
      RFLPs in Micronesians and Caucasians indicate that a universal GM allogenotyping
      procedure cannot yet be developed; instead, population-specific procedures are
      necessitated by differences in GM allotype arrangements between populations.

PMID- 1349876
TI  - HIV-1 and HIV-2 in Spain.

PMID- 1349877
TI  - Glucocorticoid receptor numbers in the brain and liver of the obese Zucker rat.
AB  - Scatchard analysis of ligand binding activity has been used to investigate type I
      and type II glucocorticoid receptor subtypes in the hippocampus, hypothalamus and
      liver of lean and genetically obese fa/fa rats. Despite normal levels of
      corticosterone in the hypothalamus and hippocampus of fa/fa rats, maximum binding
      to both type I and type II receptors was increased in the hippocampus and
      hypothalamus. The KD value of type I receptors was normal in fa/fa rats (lean
      0.13 nM, obese 0.15 nM) whereas the KD for corticosterone binding to type II
      receptors was increased (lean 0.48nM, obese 1.02nM). Adrenalectomy increased Bmax
      of type II receptors in lean rats in a time dependent manner but had no effect on
      binding to receptors of obese rats after the initial clearance of endogenous
      bound ligand. KD values were not altered by adrenalectomy in either genotype.
      There were no differences in binding of corticosterone to hepatic receptors of
      lean and obese rats seven days after adrenalectomy. The data suggests that
      glucocorticoid binding to type I and type II receptors is abnormally regulated in
      the brains of fa/fa rats.

PMID- 1349878
TI  - [Drug therapy of cardiovascular diseases and sports].

PMID- 1349880
TI  - [Swiss Society of Surgery of the Hand, 24th annual congress, Lausanne, March 23
      24, 1990 together with the Swiss Society for Thoracic and Cardiovascular Surgery,
      6th annual meeting, Zurich, April 11-13, 1991].

PMID- 1349879
TI  - Dexmedetomidine-induced ocular hypotension in rabbits with normal or elevated
      intraocular pressures.
AB  - This study covered the ocular hypotensive effects of the stereoisomers of the
      alpha 2-adrenoceptor agonist medetomidine. The dextro-isomer, dexmedetomidine, is
      known from pharmacologic experiments to be a specific, potent, and selective full
      agonist at alpha 2-adrenoceptors, whereas the levo-enantiomer seems to be almost
      inactive. Thus, the levo-isomer (0.5 mg/ml, 25 microliters) had no significant
      effect on intraocular pressure. After unilateral topical administration,
      dexmedetomidine (0.5 mg/ml, 25 microliters) lowered intraocular pressure
      bilaterally in normal rabbits and in rabbits with intraocular pressure elevated
      after laser irradiation of the pigmented trabecular band of the anterior chamber
      angle. In the treated (ipsilateral) eye of normal rabbits, a maximum decrease of
      4.6 +/- 0.6 mmHg was observed at 2 hr post treatment. In the contralateral eye,
      the maximum decrease was 4.1 +/- 0.5 mmHg at 1 hr after treatment. In rabbits
      with laser-induced elevation of intraocular pressure, the maximum decrease in
      treated hypertensive eyes was 13.5 +/- 0.3 mmHg 1 hr after dexmedetomidine
      administration. These results indicate that the selective alpha 2-adrenoceptor
      agonist, dexmedetomidine, is a potent and effective drug for decreasing
      intraocular pressure in rabbits.

PMID- 1349881
TI  - The assessment of cellular proliferation by immunohistochemistry: a review of
      currently available methods and their applications.
AB  - Immunohistochemical methods using antibodies to cell cycle-related antigens may
      be used as a means of assessing various aspects of proliferation in tissue, and
      have the important advantage of preserving the spatial orientation of
      proliferating cells in histological sections. Currently, the most widely
      available antibodies for this purpose are antibodies to bromodeoxyuridine (BrdU),
      Ki67 and antibodies to proliferating cell nuclear antigen (PCNA). BrdU is a
      thymidine analogue incorporated during the S phase of the cell cycle, which can
      be introduced by 'in vitro' incubation, and monoclonal antibodies are available
      to display its localization. Ki67 demonstrates a nuclear antigen expressed in all
      phases of the cell cycle, except G0 and early G1, but can only be applied to
      frozen tissue. PCNA is a nuclear antigen which is essential for DNA synthesis,
      two commercially available antibodies to PCNA work in paraffin-embedded tissue,
      but may have different staining characteristics under different conditions of
      fixation. The main advantages and disadvantages of these different techniques are
      discussed, together with their main applications to date.

PMID- 1349882
TI  - Immunogold labelling is a quantitative method as demonstrated by studies on
      aminopeptidase N in microvillar membrane vesicles.
AB  - Microvillar membrane vesicle preparations with varying content of aminopeptidase
      N were prepared from enterocytes of the pig small intestine. Postembedding
      immunogold labelling of aminopeptidase N was performed on these
      glutaraldehyde/paraformaldehyde-fixed, osmium tetroxide-treated and Epon-embedded
      microvillar membrane vesicles. The number of gold particles per micrometre
      microvillar membrane (labelling intensity) was calculated and compared to the
      corresponding enzymatic activity. A very close relationship was found between
      labelling intensity and aminopeptidase N activity, demonstrating that
      postembedding immunogold labelling can be used quantitatively.

PMID- 1349883
TI  - The ultrastructural immunolocalization of gamma-glutamyltranspeptidase in rat
      lung: correlation with the histochemical demonstration of enzyme activity.
AB  - gamma-Glutamyltranspeptidase (gamma-GT) was localized in slices of rat lung, at
      the ultrastructural level, by pre-embedding immunogold labelling. Antiserum was
      raised against the protein purified from rat kidney. The enzyme was found to be
      concentrated on the lumenal surface of the non-ciliated ("Clara") cells of the
      bronchiolar epithelium and, to a lesser degree, on the surface of type II
      alveolar pneumocytes. This immunological localization was consistent with the
      distribution of reaction product, in both slices and resin sections incubated to
      demonstrate gamma-GT activity. gamma-GT is probably involved in the utilization
      of reduced glutathione (GSH) present in the fluid lining the airway epithelium.

PMID- 1349884
TI  - Retail cut yields of Rambouillet wether lambs fed the beta-adrenergic agonist
      L644,969.
AB  - Twenty Rambouillet wether lambs were given ad libitum access to a diet with (BAA,
      n = 10) or without (control, n = 10) 1 ppm of the beta-adrenergic agonist
      L644,969. Lambs were fed to a constant slaughter weight end point of 54.5 kg.
      Carcasses were fabricated to yield bone-in and boneless cuts that were trimmed
      progressively to 1.27, .64, .32, and .00 cm of s.c. fat remaining. Addition of
      BAA did not affect growth traits. Actual and adjusted fat thickness, body wall
      thickness, and percentage of kidney-pelvic fat did not differ between control and
      BAA lambs. However, BAA increased longissimus muscle area, longissimus muscle
      depth, and leg score while decreasing USDA yield grade. The BAA increased carcass
      conformation scores and decreased flank lean color scores. No other carcass
      quality measurements were affected by BAA. Addition of BAA did not affect overall
      carcass yields of bone-in retail cuts. However, BAA increased overall carcass
      yields of boneless retail cuts regardless of fat trim level. The BAA increased
      bone-in leg yield. Yield of boneless sirloin, bone-in loin and boneless loin were
      not affected by BAA. For these cuts, the percentage change from the control was
      highly dependent on fat trim level. There was no difference in short-cut, shank
      off, semiboneless leg yield between control and BAA. Addition of BAA did not
      affect yield of bone-in rack regardless of fat trim level. However, BAA greatly
      increased yield of boneless ribeye. The BAA did not affect yield of bone-in or
      boneless shoulder.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349885
TI  - Effects of dietary level of lysine and of level and source of protein on feed
      intake, growth performance, and plasma amino acid pattern in the finishing pig.
AB  - The effects of dietary level of lysine and of level and source of CP on voluntary
      feed intake, growth performance, plasma free amino acids, and carcass
      characteristics were investigated in a study involving 60 female and 60 castrated
      male Large White finishing pigs (from 42 to 101 kg live weight) with ad libitum
      access to feed. Six treatments were compared according to a 2 x 3 factorial plan,
      with two levels of lysine (.55 and .65% selected below the recommended levels for
      both sexes) and three types of CP (N x 6.25) supply: a 13% CP diet based on
      wheat, peanut meal and soybean meal; a 15.6% CP diet providing the same amino
      acid pattern as that of the basal diet; and a 15.2% CP diet containing the same
      levels of essential amino acids as the 13% CP diet, with the addition of glutamic
      acid as a source of nonessential amino acids. By maintaining a constant amino
      acid pattern separate changes in dietary lysine and CP levels resulted in a
      relative independency of their effects on feed intake, growth performance, and
      body composition. Muscle gain increased with supplementary lysine, with a lower
      response at the lower CP level (13%). At the same level of lysine (.55 or .65%),
      increasing protein content from 13 to 15.6% did not affect feed intake, but
      growth rate was lower and feed/gain was increased, partly because of an
      additional energy cost resulting from catabolism of excess protein.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1349886
TI  - The role of autologous blood stem cells in support of high-dose therapy for
      multiple myeloma.
AB  - During the last few years, high-dose therapy with hemopoietic stem cell support
      has become a well-admitted therapeutic option for young patients with MM. The
      role of allogeneic or autologous graft and of blood rather than bone marrow as
      the source of hemopoietic stem cells must be further investigated. Autologous
      PBSC transplantation has, however, both practical and theoretic advantages over
      allogeneic and autologous BMT: (1) It can be applied to most patients, especially
      if blood stem cells are collected early in the course of therapy. (2) It usually
      induces relatively rapid hematologic reconstitution. (3) In comparison with
      autologous BMT, it appears to minimize the hazard of the reinfusion of malignant
      cells.

PMID- 1349887
TI  - Expression of proliferating cell nuclear antigen during the cell cycle of human
      diploid fibroblasts.
AB  - Proliferating cell nuclear antigen mRNA levels were determined in human diploid
      fibroblasts as they progressed through the cell cycle. PCNA message levels were
      low at G0, gradually increased following entrance into G1, peaked at G1/S, and
      declined during S phase. PCNA mRNA was determined to have a half life of 12 hours
      when cells were blocked at the G1/S interface. PCNA protein levels increased two-
      to three-fold as cells moved from G0 to S phase.

PMID- 1349889
TI  - Renal alpha 2-adrenoceptors in New Zealand genetically hypertensive rats.
AB  - 1. Renal alpha 1- and alpha 2-adrenoceptors were characterized in the New Zealand
      strain of genetically hypertensive (GH) rat and the Otago random-bred albino
      normotensive (NT) control rat at 4 and 12 weeks of age with [3H]-prazosin and
      [3H]-rauwolscine. 2. At 4 weeks of age, the density of alpha-adrenoceptors in NT
      and GH rats was similar to both the alpha 1- (193 +/- 11 vs 163 +/- 14 fmol mg-1
      protein) and alpha 2- (347 +/- 34 vs 319 +/- 41 fmol mg-1 protein) adrenoceptor.
      At 12 weeks of age, GH rats had a greater density of renal alpha 1- (152 +/- 27
      vs 238 +/- 17 fmol mg-1 protein) and alpha 2- (175 +/- 42 vs 350 +/- 23 fmol mg-1
      protein) adrenoceptors compared to the NT rats. 3. Pre-incubation of kidneys from
      GH rats (12 weeks of age) with 1 and 10 microM clonidine decreased the density of
      receptors identified by unlabelled clonidine displacement of [3H]-rauwolscine to
      77% and 56% of control. Pre-incubation with adrenaline, 2,6 dimethylclonidine or
      phenylephrine failed to alter binding. 4. Pre-incubation of kidneys from NT rats
      (12 weeks) or young GH rats (4 weeks) with 10 microM clonidine failed to alter
      displacement of [3H]-rauwolscine by unlabelled clonidine. 5. These studies
      demonstrate that in another strain of hypertensive rat, the GH rat, alpha 2
      adrenoceptor density is increased as compared to the normotensive control at 12
      but not 4 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349888
TI  - Pharmacological analysis of positive chronotropic and inotropic responses to
      etilefrine in isolated dog heart preparations.
AB  - Positive chronotropic and inotropic responses to etilefrine (alpha
      [(ethylamino)methyl]-m-hydroxybenzyl alcohol), an orally active cardiovascular
      agent, were investigated in isolated dog right atrial and left ventricular
      preparations. Intravenous administration of etilefrine to a support dog increased
      heart rate and mean systemic blood pressure, and increased sinus rate and atrial
      contractile force in the isolated right atrium perfused with blood from the
      support dog. Etilefrine injected intra-arterially to isolated atria and
      ventricles induced dose-dependent positive chronotropic and inotropic effects.
      Etilefrine was about 100 times less potent than isoproterenol. The effects of
      etilefrine in isolated atria were significantly inhibited by treatment with
      atenolol, but were not significantly inhibited by ICI 118,551. The effects of
      etilefrine were partially inhibited by imipramine. These results indicate that
      etilefrine is a highly selective beta-1 adrenoceptor agonist and suggest a
      moderate catecholamine-releasing activity by tyramine-like action in the blood
      perfused dog heart.

PMID- 1349890
TI  - Activation of alpha 1- and alpha 2-adrenoceptors inhibits noradrenaline release
      in rabbit renal arteries: effects of pertussis toxin and N-ethylmaleimide.
AB  - 1. The effects of selective alpha 1- and alpha 2-adrenoceptor agonists and
      antagonists on the stimulation-induced (S-I) outflow of radioactivity at 2 Hz
      were investigated in superfused rabbit renal arteries incubated with [3H]
      noradrenaline. 2. The alpha 1-adrenoceptor agonist methoxamine (10 microM)
      inhibited S-I outflow of radioactivity and this effect was abolished by the alpha
      1-adrenoceptor antagonist prazosin (0.1 microM) but not by the alpha 2
      adrenoceptor antagonist rauwolscine (1 microM). Neither the prostaglandin
      synthesis inhibitor indomethacin (10 microM) nor the adenosine receptor
      antagonist 8-phenyl-theophylline (1 microM) prevented the inhibitory effect of
      methoxamine. 3. The alpha 2-adrenoceptor agonists clonidine (0.1 microM) and UK
      14304 (0.1 microM) both inhibited S-I outflow of radioactivity. The inhibitory
      effect of clonidine was blocked by rauwolscine but not by prazosin. The
      inhibitory effect of UK 14304 was markedly reduced by rauwolscine. 4. Prazosin
      (0.1 microM) alone did not enhance the S-I outflow of radioactivity at 2 Hz and
      slightly enhanced S-I outflow at 4 Hz. Rauwolscine (1 microM) alone markedly
      enhanced S-I outflow of radioactivity at 2 and 4 Hz. 5. Pretreatment of the
      arteries with pertussis toxin (1 microgram ml-1) did not significantly alter the
      inhibitory effects of methoxamine or UK 14304 or the potentiation by rauwolscine.
      However, pretreatment of the arteries with a higher concentration of pertussis
      toxin (5 micrograms ml-1) prevented the inhibitory effect of methoxamine but
      still did not affect the responses to UK 14304 and rauwolscine. 6. Pretreatment
      of the arteries with N-ethylmaleimide (NEM, 10 microM) for 30 min did not alter
      the inhibitory effect of methoxamine but markedly attenuated the inhibitory
      effect of UK 14304 and the facilitatory effect of rauwolscine. 7. The results
      suggest that both alpha 1- and alpha 2-adrenoceptors take part in the modulation
      of noradrenaline release from sympathetic nerves in rabbit renal arteries. Alpha
      1-adrenoceptor mediated inhibition may be coupled to G-proteins which are
      pertussis toxin sensitive and alpha 2-adrenoceptor mediated inhibition to G
      proteins which are NEM-sensitive.

PMID- 1349891
TI  - Reversal of multidrug resistance by B859-35, a metabolite of B859-35,
      niguldipine, verapamil and nitrendipine.
AB  - It has been shown previously that verapamil and other calcium antagonists and
      calmodulin inhibitors can reverse multidrug resistance. We compared the potency
      of the dihydropyridine derivatives (4R)-3-[3-(4,4-diphenyl-1-piperadinyl)-propyl]
      5-methyl-1,4-dihydr o-2,6- dimethyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate
      hydrochloride (B859-35), a metabolite of B859-35, niguldipine and (R)
      nitrendipine to that of (RS)-verapamil in reversing multidrug resistance. The
      accumulation of the fluorescent dye rhodamine 123, which is transported by the P
      glycoprotein, was determined by a flow cytometer. Multidrug-resistant human HeLa
      KB-8-5 and Walker rat carcinoma cells were incubated in the presence and in
      absence of the drugs indicated above. We found that 0.1 microM B859-35 increases
      the accumulation of rhodamine 123 in multidrug-resistant KB-8-5 and Walker cells
      more effectively than 1 microM (RS)-verapamil. In sensitive KB-3-1 cells addition
      of the drugs had no significant influence on the accumulation of rhodamine 123.
      IN KB-8-5 cells, 10 nM Adriamycin caused a reduction of cell growth to 85%
      compared to untreated controls (= 100%). If 1 microM B859-35, B859-35 metabolite,
      niguldipine, verapamil or (R)-nitrendipine was added to 10 nM Adriamycin, growth
      reduction compared with untreated controls increased to 12%, 11%, 23%, 63%, and
      82% respectively. The effect of 0.1 microM B859-35 was a reduction in
      proliferation to 38%, that of 0.1 microM verapamil to 72%. These data illustrate
      that B859-35, a compound with antitumor activity in several tumors, is at least
      ten times more potent than racemic verapamil in reversing multidrug resistance.

PMID- 1349892
TI  - Expression and release of phosphatidylinositol anchored cell surface molecules by
      a cell line derived from sensory neurons.
AB  - Early postnatal mouse dorsal root ganglion neurons were found to express several
      glycosylphosphatidylinositol-anchored (GPI) molecules from the immunoglobulin
      superfamily (neural cell adhesion molecule 120 kD isoform, F3, Thy1) whose
      expression is developmentally regulated. A hybrid cell line (ND26), made by
      fusing postmitotic rat dorsal root ganglion (DRG) neurons with the mouse
      neuroblastoma N18Tg2, could be induced to differentiate by manipulating the
      composition of the culture medium and expressed similar GPI molecules to DRG
      neurons. We used this model system to investigate the metabolism of GPI-anchored
      molecules. We found that neural cell adhesion molecule 120 Kd isoform expression
      decreased upon differentiation, whereas the level of F3 and Thy1 increased,
      suggesting a role in neurite outgrowth processes. The ratio of molecules
      cleavable by exogenous phosphatidylinositol phospholipase C (PI-PLC) was similar
      for all the GPI-anchored molecules, which could mean that cell-specific
      modifications of the basic anchoring structure determine the level of potentially
      releasable molecules. Measurements of spontaneous release indicated that this
      reflected the overall level of expression of these molecules by the ND26 cell
      line. Finally, we observed an effect of dibutyryl cAMP on the level of expression
      of F3 and Thy1 but not of N-CAM. However, we could not detect any significant
      effect of nerve growth factor (NGF) either on the level of expression or on the
      amount of spontaneously released molecules.

PMID- 1349893
TI  - Acetyl-CoA carboxylase in Reuber hepatoma cells: variation in enzyme activity,
      insulin regulation, and cellular lipid content.
AB  - Reuber hepatoma cells are useful cultured lines for the study of insulin action,
      lipid and lipoprotein metabolism, and the regulation of acetyl-CoA carboxylase
      (ACC), the rate-limiting enzyme of fatty acid biosynthesis. During investigations
      in different clonal lines of these cells, we have uncovered marked intercellular
      variability in the activity, enzyme content, and insulin regulation of ACC
      paralleled by differences in cellular neutral lipid (triglyceride) content. Two
      contrasting clonal lines, Fao and H356A-1, have been studied in detail. Several
      features distinguish these two lines, including differences in ACC activity and
      enzyme kinetics, the content of the two major hepatic ACC isozymes (Mr 280,000
      and 265,000 Da) and their heteroisozymic complex, the extent of ACC
      phosphorylation, and the ability of ACC to be activated on stimulation by insulin
      and insulinomimetic agonists. As studied by Nile Red staining and fluorescence
      activated cell sorting, these two lines also display marked differences in
      neutral lipid content, which correlates with both basal levels of ACC activity
      and inhibition of ACC by the fatty acid analog, 5-(tetradecyloxy)-2-furoic acid
      (TOFA). These results emphasize the importance of characterization of any
      particular clonal line of Reuber cells for studies of enzyme regulation,
      substrate metabolism, and hormone action. With respect to ACC, studies in
      contrasting clonal lines of Reuber cells could provide valuable clues to
      understanding both the complex mechanisms of intracellular ACC regulation in the
      absence and presence of hormones and its regulatory role(s) in overall hepatic
      lipid metabolism.

PMID- 1349894
TI  - An investigation of the association of benzodiazepines and other hypnotics with
      the incidence of falls in the elderly.
AB  - Clinical and medication data from 2,878 admissions to a Department for Care of
      the Elderly were examined retrospectively to determine the association between
      the administration of hypnotics/benzodiazepines and the incidence of falls. Only
      lorazepam prescribed to females and nitrazepam prescribed to males were
      associated with a significantly increased incidence of falls. Women fell
      significantly more frequently than men, and 7.5% of falls resulted in fractures.
      Stroke was the most common major diagnosis in fall-cases, followed by infection,
      Parkinsonism and confusion.

PMID- 1349895
TI  - An office-based approach to the patient with pruritus.

PMID- 1349896
TI  - Determination of the enantiomers of fenoldopam in human plasma by reversed-phase
      high-performance liquid chromatography after chiral derivatization.
AB  - Fenoldopam, a selective agonist at peripheral dopaminergic (DA-1) receptors, is
      administered as a racemic mixture and, consequently, an indirect stereospecific
      high-performance liquid chromatographic assay was developed to study the
      disposition of the individual enantiomers in human subjects. Fenoldopam
      enantiomers were extracted from alkalinized plasma into ethyl acetate prior to
      precolumn derivatization with the chiral reagent 2,3,4,6-tetra-O-acetyl-beta-D
      glucopyranosyl isothiocyanate (GITC). The resulting diastereomers were separated
      on a reversed-phase butylsilica column and determined using triple-electrode
      coulometric detection. The limits of determination and detection for the S- and R
      enantiomers of fenoldopam were 0.5 and 0.25 ng/ml, respectively. A linear
      response was observed for (S)- and (R)-fenoldopam concentrations ranging from 0.5
      to 50 ng/ml in plasma. The intra-day relative standard deviations (R.S.D.s) for
      the plasma assay at nominal concentrations of 0.5, 5 and 50 ng/ml were 17.4, 5.2
      and 6.9%, respectively, for (S)-fenoldopam and 9.9, 6.2 and 7.4%, respectively,
      for (R)-fenoldopam. The inter-day R.S.D.s of the method at these concentrations
      were 9.3, 7.7 and 7.4%, respectively, for (S)-fenoldopam and 9.5, 1.9 and 7.3%,
      respectively, for (R)-fenoldopam. The mean accuracy of the method at
      concentrations of 0.5, 5 and 50 ng/ml in plasma was found to be 106.4, 111.8 and
      108.9%, respectively, for (S)-fenoldopam and 116.2, 104.2 and 111.2%,
      respectively, for (R)-fenoldopam. The assay developed was sufficiently sensitive,
      accurate and precise to support pharmacokinetic studies in human subjects.

PMID- 1349897
TI  - Extensive allelic variation in Cryptococcus neoformans.
AB  - The orotidine monophosphate pyrophosphorylase (OMPPase) gene locus of the DNA of
      13 Cryptococcus neoformans var. neoformans strains, including 10 recent clinical
      isolates, was studied by using restriction fragment length polymorphisms and
      nucleotide sequence analysis. The OMPPase locus (URA5) is highly polymorphic, and
      at least six alleles were identified. The nucleotide sequences of some alleles
      differed by up to 5%. The majority of the nucleotide polymorphisms in the protein
      coding region occurred at the third codon position and were silent. The low
      frequency of replacement nucleotide substitutions relative to silent nucleotide
      substitutions implied that there is strong selection against amino acid changes
      in OMPPase. The allelic variation suggested that there is extensive genomic
      diversity among C. neoformans clinical isolates from one geographic area. The
      various alleles are potentially useful markers in the study of the population
      structure, epidemiology, and pathogenesis of C. neoformans strains.

PMID- 1349898
TI  - Use of a dispersed repetitive DNA element to distinguish clinical isolates of
      Cryptococcus neoformans.
AB  - We isolated a recombinant phage from a Cryptococcus neoformans genomic library
      that contains a member of a dispersed family of repetitive DNA elements. This
      clone, CNRE-1, hybridized to at least seven chromosomes in C. neoformans on the
      basis of pulsed-field gel analysis. Hybridization of CNRE-1 to restriction
      digests of genomic DNA confirmed that there are multiple copies of this element
      and that restriction fragment length polymorphisms are present in strains from
      different serotypes of C. neoformans. The utility of this probe as an
      epidemiologic marker was determined by testing cryptococcal isolates from a
      single hospital. Five isolates from four patients were closely related to a
      serotype A reference strain, whereas five other isolates from four additional
      patients exhibited distinct patterns. In two patients, the isolates obtained
      during recurrent cryptococcal infections were identical to the original isolates.

PMID- 1349899
TI  - Two-step polymerase chain reactions and restriction endonuclease analyses detect
      and differentiate ompA DNA of Chlamydia spp.
AB  - Specific and sensitive amplification of major outer membrane protein (MOMP) gene
      (ompA) DNA sequences of Chlamydia species with various MOMP genotypes was
      achieved by a two-step polymerase chain reaction (PCR). Degenerate, inosine
      containing oligonucleotide primers homologous to the 5' and 3' ends of the
      translated regions of all chlamydial MOMP genes were used in a PCR to amplify a
      DNA fragment of approximately 1,120 bp. A portion of this DNA fragment was
      amplified in a second genus-specific reaction that yielded a DNA fragment of
      approximately 930 bp. A pair of degenerate oligonucleotide primers homologous to
      internal sequences of the primary DNA fragment was used in this PCR. This method
      detected three cognate chlamydial genomes in a background of 1 microgram of
      unrelated DNA. MOMP genes of 13 representative chlamydial MOMP genotypes of the
      species C. trachomatis, C. pneumoniae, and C. psittaci were amplified. In a
      secondary PCR, group-specific detection was achieved by the simultaneous use of
      one genus-specific primer and three primers derived from different fingerprint
      regions of three major groups of chlamydiae. This multiplex PCR differentiated
      the groups by the length of the amplified DNA fragments and detected the
      simultaneous presence of DNA sequences of the Chlamydia spp. with different MOMP
      genotypes. Further differentiation as ompA restriction fragment length
      polymorphism types among all chlamydial strains with the various MOMP genotypes
      analyzed here was achieved by restriction endonuclease analysis of the secondary
      PCR products. DNA sequences corresponding to the ompA restriction fragment length
      polymorphism type B577 of C. psittaci were detected in two of seven milk samples
      from cases of bovine mastitis.

PMID- 1349900
TI  - Rapid and specific detection of the pap, afa, and sfa adhesin-encoding operons in
      uropathogenic Escherichia coli strains by polymerase chain reaction.
AB  - Adhesin-encoding operons (pap, sfa/foc, and afa) have been shown to be prevalent
      in Escherichia coli strains associated with urinary tract infections. A quick and
      sensitive assay to identify these operons was developed by using the polymerase
      chain reaction (PCR). Three pairs of 25-mer primers were defined from the
      sequences of the DNA fragments used as probes in hybridization studies to
      identify each of the three operons, and the six primers were used together in a
      single reaction of amplification. To validate the PCR approach for detection of
      adhesin-encoding operons among clinical isolates, we investigated a collection of
      97 E. coli isolates with the following characteristics: all isolates originated
      from the urine of patients with pyelonephritis, and the adhesin responsible for
      specific binding of the isolates to uroepithelial cells was previously
      characterized by phenotypic assays, as well as genotypic tests based on
      hybridization. There was a perfect correlation between the results obtained with
      the PCR approach and those previously obtained by using DNA probes. These results
      indicate that the PCR method, which is highly specific and easier to perform than
      the hybridization method, is a powerful genotypic assay for detection of adhesin
      encoding operons. Thus, this assay can be recommended for clinical use to detect
      virulent urinary E. coli strains, as well as for epidemiological studies.

PMID- 1349902
TI  - Dust mite allergens and asthma: report of a second international workshop.

PMID- 1349901
TI  - Ribosomal DNA probe for differentiation of Babesia microti and B. gibsoni
      isolates.
AB  - The objective of this study was to determine whether different isolates of
      Babesia microti could be distinguished from morphologically similar isolates of
      B. gibsoni by using a ribosomal DNA (rDNA) probe. A Babesia-specific rDNA probe
      was obtained by polymerase chain reaction amplification of sequences from B.
      microti DNA using universal primers directed against highly conserved portions of
      the eukaryotic 16S-like rRNA gene. The chemiluminescent rDNA probe hybridized to
      Southern blots of restriction endonuclease-digested DNA preparations of different
      isolates of B. gibsoni from infected dogs and B. microti from infected humans and
      white-footed mice. Restriction fragment length polymorphisms served to
      differentiate these species. Although the hybridization patterns seen with DNAs
      from six B. microti isolates did not vary, those of the five B. gibsoni isolates
      did indicate genotypic variation. We concluded that isolates of B. microti and B.
      gibsoni can be differentiated on the basis of restriction fragment length
      polymorphism detected with a chemiluminescent rDNA probe.

PMID- 1349903
TI  - [Study of the immune profile of pregnant women].
AB  - During pregnancy, the fetus is an hemiallograft perfectly tolerated by the
      mother. With the aim of elucidating the mechanism of this tolerance, we have
      looked to see whether lymphocyte subsets are modified by pregnancy. Using
      monoclonal antibodies and flow cytometry, we have studied the changes in the
      immune profile of normal pregnant women and compared them with non pregnant
      women. In pregnant women, a significant decrease in the percentage of CD3+ cells
      is observed in the first trimester (61.1 +/- 14.7% versus 73.8 +/- 6.8%; p less
      than 0.001). The same data are obtained for CD4+ cells (38.2 +/- 10.7% versus
      44.0 +/- 7.0%; p less than 0.05) and CD8+ cells (22.8 +/- 5.6% versus 28.0 +/-
      8.9%; p less than 0.05). On the other hand, B lymphocytes (CD19+), monocytes (Leu
      M3+) and natural killer (NK) cells (Leu7+) remain stable during pregnancy. CD11a+
      cells decreased during the 1st and 2nd trimesters. Lastly, activated T
      lymphocytes (CD3+DR+, CD8+DR+) are not modified. Using absolute numbers, a
      significant decrease is shown only for CD3+ cells in the 2nd and 3rd trimesters
      and for CD11a+ cells in the 2nd trimester of pregnancy. The decrease of T
      lymphocyte subsets, NK and CD11a+ cells during pregnancy partially explains the
      tolerance for the fetus.

PMID- 1349904
TI  - The effect of antihypertensive drugs on in vivo platelet activity in essential
      hypertension.
AB  - OBJECTIVE: To investigate whether antihypertensive drugs have a beneficial effect
      upon the abnormal in vivo platelet function found in patients with essential
      hypertension. DESIGN: A cross-sectional study in which plasma beta
      thromboglobulin, a marker of in vivo platelet activation, was measured in
      patients with essential hypertension on various antihypertensive drugs. All were
      free from any other diseases which might affect platelet function. METHODS:
      Plasma beta-thromboglobulin was measured in 24 patients with untreated essential
      hypertension, 21 normotensive control patients, 16 patients receiving angiotensin
      converting enzyme (ACE) inhibitors, 16 patients receiving a beta-adrenoceptor
      blocker, 12 patients receiving calcium antagonists and 12 patients receiving a
      diuretic alone. RESULTS: Untreated hypertensives had significantly elevated
      plasma beta-thromboglobulin levels compared with controls. Plasma beta
      thromboglobulin levels in patients receiving beta-blockers and diuretics were not
      significantly different from untreated hypertensives. Treatment with calcium
      antagonists was associated with lower plasma beta-thromboglobulin levels, but
      this difference was not statistically significant. In contrast, treatment with
      ACE inhibitors was associated with significantly lower plasma beta
      thromboglobulin levels compared with untreated hypertensives. CONCLUSION: These
      results suggest that antihypertensive drugs have different effects upon abnormal
      in vivo platelet function in patients with essential hypertension. The apparent
      beneficial effect of ACE inhibitors may mean that they have more impact than
      other drug groups in the prevention of coronary heart disease.

PMID- 1349905
TI  - Increased binding of urease by activated eosinophils. Reassessment of an ELISA
      for CD11b.

PMID- 1349906
TI  - Incidence of Mycobacterium avium-intracellulare complex bacteremia in human
      immunodeficiency virus-positive patients.
AB  - The product-limit incidence of Mycobacterium avium-intracellulare complex (MAC)
      bacteremia in 1006 human immunodeficiency virus (HIV)-positive patients followed
      at one institution over a 3-year period from the day of AIDS diagnosis with
      monthly lysis-centrifugation blood cultures was 21% +/- 2% SE at 1 year and 43%
      +/- 3% at 2 years. The product-limit incidence of MAC bacteremia at 1 year after
      the patients' first CD4 cell count was related to both the CD4 cell count and to
      whether they had an AIDS diagnosis (both P less than .0001) but not to age, sex,
      or race. This incidence was 39% +/- 6% for CD4 cell counts of less than 10/mm3,
      30% +/- 5% for 10-19/mm3, 20% +/- 4% for 20-39/mm3, 15% +/- 4% for 40-59/mm3, 8%
      +/- 3% for 60-99/mm3, and 3% +/- 1% for 100-199/mm3. MAC may eventually infect
      most if not all HIV-positive patients who do not die from another HIV-related
      event.

PMID- 1349907
TI  - Preliminary study on oncogene product immunohistochemistry (c-erbB-2, c-myc, ras
      p21, EGFR) in breast pathology.
AB  - The expression of oncogene products related to cell growth (c-erbB-2, c-myc, ras
      p21, EGFR) was investigated in benign (15 cases) and malignant breast lesions (20
      cases) by means of immunohistochemistry using the avidin-biotin-peroxidase
      technique with polyclonal and monoclonal antibodies. The aim of this study was to
      evaluate the relationship between the staining positivity and various
      morphological and biological features, such as tumour type, grading, hormone
      receptor status and cell kinetic parameters. In benign breast lesions, as
      expected, the kinetic parameters were low, both for Ki-67 and LI. All the
      specimens showed a diploid condition (the DI being equal to 1) and we found a
      limited degree of immunoreactivity for all the growth factors and oncogene
      products. In breast cancer we studied the distribution of immunohistochemical
      positivity for EGFR, c-erbB-2, c-myc, ras p21 and Ki-67, which was related to
      age, nodal status, ER and PgR receptor status, LI, DI and histopathological
      grading. A significant positive correlation was found both between ras p21
      expression and nodal status and ER-ICA positivity. We observed a strong
      correlation between LI and Ki-67 and an inverse relation between Ki-67 and ER
      expression. These findings suggest the importance of studying the relationship
      between prognostic factors which may provide preoperative prediction in the
      biological behaviour of breast cancer, not only on biopsy specimens, but also on
      fine needle aspirates.

PMID- 1349908
TI  - Preliminary evaluation of HER-2/neu oncogene and epidermal growth factor receptor
      expression in normal and neoplastic human ovaries.
AB  - The HER-2/neu oncogene (a member of the Erb-like oncogene family) is distinct
      from but closely related to the c-erb B gene which encodes the epidermal growth
      factor receptor (EGFr). HER-2/neu gene amplification was found in a large number
      of mammary carcinomas and there was a strong correlation between this phenomenon
      and poor prognosis. In our study HER-2/neu oncogene expression was determined in
      16 malignant ovarian tumors, 2 ovarian lymphomas and 5 normal ovaries. The HER
      2/neu gene was found both in normal ovaries and malignant tumors, without any
      apparent difference among the various histological types. In all the specimens
      examined, HER-2/neu expression did not seem to be related to EGF binding
      capacity.

PMID- 1349909
TI  - Identification of somatostatin-14 and -28 in rat pancreatic juice by a new HPLC
      method.
AB  - Recently we could demonstrate that in rats with pancreatic hypertrophy,
      somatostatin is secreted in higher concentrations into the pancreatic juice than
      into the portal vein blood. For measurement of juice somatostatin and to
      characterize the molecular forms, we established a new reverse-phase HPLC method,
      which we describe herein. This HPLC method, using a linear gradient system
      consisting of 0.2% heptafluorbutyric acid in 10 mM sodium acetate and
      acetonitrile, showed a stable recovery rate of about 85%. Applying the pure juice
      to this gradient system, we detect somatostatin-14 to be the major form of
      immunoreactive somatostatin (IRSS) in the pancreatic juice of the rat (5% of
      total IRSS). The remaining 35% were found to be somatostatin-28. The role of
      somatostatin in pancreatic juice is not known. It raises the hypothesis that it
      possibly interacts with the influences intraluminal intestinal growth factors.
      This study supports the assumption for the existence of an insuloacinar portal
      system to regulate exocrine pancreatic functions by islet hormones.

PMID- 1349910
TI  - Microtiter assay for measurement of factor XIII activity in plasma.
AB  - A sensitive, reproducible and rapid quantitative microtiter assay for factor XIII
      activity is described. The assay is based on incorporation of a soluble amine
      substrate into casein attached to polystyrol microtiter plates and detection of
      bound substrate with a monoclonal antibody-enzyme conjugate. Defibrination of
      plasma samples is not required. The assay shows strong correlation with the
      immunologic assay for factor XIII catalytic subunit a (r = 0.94), the factor XIII
      dansylcadaverine assay (r = 0.83), and the factor XIII clot solubility test.
      Normal values detected in healthy blood donors were in the range of 74% to 117%,
      with a mean value of 96.9% and a median value of 97.8%; pooled normal plasma was
      used as a reference. Since the assay is performed in a single microtiter plate
      and requires few reagents and short incubation periods, it can be easily adapted
      for clinical use.

PMID- 1349911
TI  - Pharmaco-morbidity linkage: a feasibility study comparing morbidity in two
      pharmacy based exposure cohorts.
AB  - STUDY OBJECTIVES: The aims were (1) to compare discharge diagnoses and concurrent
      medication in a pharmacy based cohort of users of H2 receptor antagonists to
      those in a population of users of other drugs in the same period, who did not use
      H2 receptor antagonists; (2) to compare these results to those of a similar study
      performed with the Tayside record linkage scheme. DESIGN AND SETTING: The study
      was a retrospective cohort study. The morbidity data from the only hospital in
      one medium sized city (62,000 inhabitants) were linked to the dispensing data of
      all five community pharmacies on an individual basis (April 1, 1986-December 31,
      1989). In the absence of a unique patient identification number, data from
      pharmacies and hospital were linked by the combination of date of birth, gender,
      and general practitioner code. For every user of H2 receptor antagonists two
      controls were obtained from all patients who had not used these drugs, and
      matched for age (within 5 years), gender, and general practitioner. All discharge
      diagnoses which followed this first prescription up to December 31, 1989, in a
      patient in the index cohort, and during the same period in his or her matched
      controls, were included in the study. MAIN RESULTS: In the index cohort (n =
      2174) 341 persons were admitted (526 admissions) as against 398 persons (527
      admissions) in the control cohort (n = 4348). There was increased morbidity in
      the index cohort, especially concerning the gastrointestinal system (peptic
      ulcers and malignancies, abdominal pain, gastrointestinal haemorrhage), but also
      concerning the musculoskeletal, respiratory, and circulatory systems. The
      morbidity in the last three groups corresponded with drugs used concomitantly by
      patients in the index cohort, so it was probably not causally related to the
      intake of H2 receptor antagonists but was rather an indicator of higher levels of
      morbidity in the index cohort. CONCLUSIONS: The figures were grossly comparable
      to those of the Tayside record linkage scheme. Probabilistic linking with the
      patient characteristics of gender, date of birth, and general practitioner code
      can facilitate the undertaking of postmarketing surveillance studies.

PMID- 1349912
TI  - Comparison of messenger RNA pools in active and dormant Artemia franciscana
      embryos: evidence for translational control.
AB  - In response to environmental anoxia, embryos of the brine shrimp Artemia
      franciscana enter a dormant state during which energy metabolism and development
      are arrested. The intracellular acidification that correlates with this
      transition into anaerobic dormancy has been linked to the inhibition of protein
      synthesis in quiescent embryos. In this study, we have addressed the level of
      control at which a mechanism mediated by intracellular pH might operate to arrest
      protein synthesis. Two independent lines of evidence suggest that there is an
      element of translational control when protein synthesis is arrested in dormant
      embryos. First, as determined by in vitro translation techniques, there were no
      significant quantitative differences in mRNA pools in dormant as compared to
      actively developing embryos. In addition, fluorography of the translation
      products showed that there are no large qualitative changes in mRNA species when
      embryos become dormant. These data suggest that there was no net degradation of
      mRNA pools in dormant embryos and that protein synthesis may therefore be
      controlled more strongly at translation than at transcription. Second, polysome
      profile studies showed that dormant embryos possess reduced levels of polysomes
      relative to those found in cells or active embryos. The disaggregation of
      polysomes is an indication that the initiation step in protein synthesis is
      disrupted and is further evidence that the mechanism involved in protein
      synthesis arrest in dormant Artemia involves translational control.

PMID- 1349913
TI  - The role of microtubules in contractile ring function.
AB  - During cytokinesis, a cortical contractile ring forms around a cell, constricts
      to a stable tight neck and terminates in separation of the daughter cells. At
      first cleavage, Ilyanassa obsoleta embryos form two contractile rings
      simultaneously. The cleavage furrow (CF), in the animal hemisphere between the
      spindle poles, constricts to a stable tight neck and separates the daughter
      cells. The third polar lobe constriction (PLC-3), in the vegetal hemisphere below
      the spindle, constricts to a transient tight neck, but then relaxes, allowing the
      polar lobe cytoplasm to merge with one daughter cell. Eggs exposed to taxol, a
      drug that stabilizes microtubules, before the CF or the PLC-3 develop, fail to
      form CFs, but form stabilized tight PLCs. Eggs exposed to taxol at the time of
      PLC-3 formation develop varied numbers of constriction rings in their animal
      hemispheres and one PLC in their vegetal hemisphere, none of which relax. Eggs
      exposed to taxol after PLC-3 initiation form stabilized tight CFs and PLCs. At
      maximum constriction, control embryos display immunolocalization of
      nonextractable alpha-tubulin in their CFs, but not in their PLCs, and reveal, via
      electron microscopy, many microtubules extending through their CFs, but not
      through their PLCs. Embryos which form stabilized tightly constricted CFs and
      PLCs in the presence of taxol display immunolocalization of nonextractable alpha
      tubulin in both constrictions and show many polymerized microtubules extending
      through both CFs and PLCs. These results suggest that the extension of
      microtubules through a tight contractile ring may be important for stabilizing
      that constriction and facilitating subsequent cytokinesis.

PMID- 1349914
TI  - Reported association of akathisia with suicide.

PMID- 1349916
TI  - National Chaplain's address at the AGM (Annual General Meeting).

PMID- 1349915
TI  - Laboratory colonization and maintenance of Toxorhynchites moctezuma.
AB  - A colony of Toxorhynchites moctezuma was established at the Caribbean
      Epidemiology Centre in Trinidad in 1984. Toxorhynchites moctezuma was maintained
      in cages with high humidities. Eggs were deposited most frequently in a cut
      bicycle tire containing water. A minimum of 42 h was required for hatching, but
      94% hatched between 43 and 51 h. Aedes aegypti larvae were supplied as prey.
      Larval development times varied with the quantity of prey offered, but when fed
      ad lib, peak developmental time was 18 days. Mean pupal developmental time was
      5.5 days. Although only 12% of larvae survived to pupation in 3 years of
      production, our experience indicates this species would be a likely candidate for
      mass production and release.

PMID- 1349917
TI  - 2nd annual meeting of the Society for Technology in Anesthesia. San Diego,
      California, January 30-February 1, 1992. Abstracts.

PMID- 1349918
TI  - Serum dipeptidyl peptidase (DPP) IV activity in hamster buccal pouch
      carcinogenesis with 9,10-dimethyl-1,2-benzanthracene.
AB  - Dynamic change of serum DPP IV activity in carcinogenesis of hamster buccal pouch
      epithelium with DMBA was investigated. The serum enzyme level in hamster (21.5 +/
      3.1 IU/l serum) was decreased gradually from the 8th to the 10th wk when
      papillomas were induced by DMBA application (18.9 +/- 2.7 IU/l serum). The enzyme
      level was further decreased in the formation of carcinoma in situ or early
      invasive carcinoma (13.2 +/- 0.5 IU/l serum), and reached to less than half of
      the normal level at the time when tumors were diagnosed as squamous cell
      carcinoma histologically (8.1 +/- 1.3 IU/l serum). This enzyme level was
      increased by tumor excision and decreased again by tumor recurrence toward death.
      These findings suggested that the decrease of serum DPP IV activity occurred from
      the early stage of hamster buccal pouch carcinogenesis as a tumor-burden marker.

PMID- 1349919
TI  - The adrenergic pharmacology of sympathetically-maintained pain.
AB  - The authors seek to highlight some of the recent advances in understanding the
      pharmacology and pathophysiology of sympathetically-maintained pain, and to
      develop alternate, and possibly more specific, diagnostic tests for this
      phenomenon. Mechanical hyperalgesia in sympathetically-maintained pain can be
      explained by central sensitization so that the activation of A-beta
      mechanoreceptors now causes pain. The sensitization of central pain-signaling
      neurons is dynamic and reversible. The authors propose that an ongoing input from
      peripheral nociceptive afferents is necessary to maintain central sensitization.
      This nociceptive input may be due to an alpha-adrenoceptor mediated excitatory
      action of sympathetic efferents on sensory nerves that is independent of
      neurovascular transmission.

PMID- 1349920
TI  - Reduction of left ventricular hypertrophy after longterm antihypertensive
      treatment with doxazosin.
AB  - The aim of this study was to evaluate the effect of antihypertensive treatment
      with doxazosin on left ventricular anatomy and function. Therefore, after 4 weeks
      of washout with placebo (phase 1), doxazosin (dosage range from 1 to 16 mg, plus
      hydrochlorothiazide when necessary) was given to 11 essential hypertensive
      patients (6 M, 5 F, age range 34-63 years) for 8 weeks (phase 2) in order to
      achieve diastolic blood pressure values less than 90 mmHg; this dosage was then
      maintained for a further 20 weeks up to the end of the study (phase 3). Blood
      pressure was significantly reduced (Anova P less than 0.05), while heart rate did
      not change. A significant reduction of left ventricular mass index (from 128.5 +/
      26 to 114 +/- 23 g/m2, at the end of phase 1 and 3 respectively, P less than
      .001)) was observed. Before and during treatment left ventricular systolic
      function, both at rest and during stress (handgrip and cold pressor tests),
      evaluated by fractional shortening as related to end-systolic stress, in every
      case within 95% confidence limits, was calculated in normal subjects. Diastolic
      function, as evaluated by the ratio between peak early and atrial velocities of
      transmitral flow examined by pulsed doppler was significantly improved. Plasma
      catecholamine concentrations, plasma renin activity and plasma aldosterone did
      not change. A significant reduction of plasma cholesterol concentration was
      observed. These results confirm that doxazosin is a well tolerated and effective
      antihypertensive drug, with a favourable effect on blood lipids and they indicate
      that its longterm administration can induce a significant reduction of left
      ventricular mass.

PMID- 1349921
TI  - Highly polymorphic XbaI RFLPs of the human 21-hydroxylase genes among Chinese.
AB  - A highly polymorphic XbaI restriction site flanking the human 21-hydroxylase
      genes (21-OHA and 21-OHB) was found with the probe pC21/3c, the cDNA of the 21
      hydroxylase gene. From the results of RFLP analysis of 10 subjects with
      congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency and their
      parents, at least four polymorphic fragments (30 kb, 27 kb, 25 kb, and 15 kb)
      resulting from cleavage at the polymorphic endonuclease sites outside the genes
      were found, and at least 10 different polymorphic patterns were observed among
      Chinese. These results indicate that these polymorphic loci are very informative
      for prenatal diagnosis of 21-hydroxylase deficiency.

PMID- 1349922
TI  - A strategy for the rapid isolation of new PCR based DNA polymorphisms.

PMID- 1349923
TI  - Familial screening for genetic haemochromatosis by means of DNA markers.
AB  - Genetic haemochromatosis (HFE) is a frequent and potentially fatal disease. Early
      phlebotomies may prevent complications. The recessive gene for HFE is unknown but
      closely linked to the HLA-A locus. No direct test for homozygosity for HFE is
      currently available, apart from HLA typing within the family of a patient with
      confirmed HFE. During a reverse genetic approach to identify the gene, we found
      three anonymous genomic probes (P3, P5, and I.82) derived from previously cloned
      YACs and physically mapped in the HLA class I region. P3 and P5 probes recognise
      3 loci (P3A, P3B, P5) and I.82 one locus about 100 kb from HLA-A. Using five
      biallelic polymorphisms (I.82/BglII, P3B/EcoRV, P3B/PstI, P5/HindIII, P3A/PstI),
      we tested 198 HLA typed subjects from the families of 22 haemochromatosis
      patients. The information from the five polymorphisms was sufficient to identify
      unequivocally extended restriction haplotypes in all families. The restriction
      haplotypes cosegregate with the HFE allele and enable identification of
      genotypically identical sibs in all families studied. The linked DNA markers
      described in this article avoid the disadvantages of HLA serological typing and
      can be used in genetic counselling of HFE families.

PMID- 1349924
TI  - The molecular genetics of Alport syndrome: report of two workshops.

PMID- 1349925
TI  - Symposium on epidermolysis bullosa.

PMID- 1349926
TI  - Analysis of murine major histocompatibility complex class II-restricted T-cell
      responses to the flavivirus Kunjin by using vaccinia virus expression.
AB  - The present paper analyzes the influence of major histocompatibility complex
      (MHC) class II (Ir) genes on MHC class II-restricted T-cell responses to West
      Nile virus (WNV) and recombinant vaccinia virus-derived Kunjin virus antigens and
      identifies the immunodominant Kunjin virus antigens. Generally, mice were primed
      by intravenous infection with WNV or Kunjin virus, and their CD4+ T cells were
      stimulated in vitro 14 days later with WNV or Kunjin virus antigens to pulse
      macrophage or B-cell antigen-presenting cells (APC). WNV-specific in vitro T-cell
      responses from H-2b mice were higher than those from H-2d, H-2k, and H-2q mice.
      When recombinant vaccinia virus-derived Kunjin virus antigen preparations were
      tested in vitro, Kunjin virus-immune T cells of H-2b haplotype responded most
      strongly to structural (prM, C, E) and membrane-associated nonstructural (NS1)
      proteins encoded by VKV 1031 and showed weaker responses to cytosolic
      nonstructural protein NS5 (VKV 1022), whereas the responders of H-2k haplotype
      responded most strongly to the antigens encoded by VKV 1022 and gave lesser
      responses to VKV 1031. H-2d T cells gave weaker responses than either H-2b or H
      2k cells, with responses to VKV 1031 generally being higher than those to VKV
      1022. Responses to VKV 1023 or VKV 1024 encoding all of the NS3 to NS5 gene
      sequence or to VKV 1023 encoding all of NS3 were weak or absent. Within a given
      inbred strain, B cells and macrophages differed in their abilities to present
      recombinant vaccinia virus-derived Kunjin virus antigens, both in terms of
      magnitude of T-cell responses induced and the particular Kunjin virus protein
      presented. T cells from different non-MHC genetic backgrounds varied in their
      requirements of macrophage numbers as APC for maximum reactivity, suggesting that
      the concentration of class II MHC antigens and other molecules affecting APC-T
      cell interaction varied in mice with different genetic backgrounds. Regardless of
      MHC haplotype, responses to VKV 1024, which encompasses VKV 1023 and VKV 1022,
      were either absent or lower than those to VKV 1022, possibly reflecting
      differences in the processing requirements of these two proteins. When mice were
      primed intravenously with recombinant vaccinia virus and when their CD4+ T cells
      were stimulated in vitro with native Kunjin virus antigens, VKV 1031 primed more
      efficiently than Kunjin virus and VKV 1022 primed similarly to Kunjin virus.

PMID- 1349927
TI  - Alterations of the p53 gene in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a malignancy which is consistently associated
      with the Epstein-Barr virus (EBV). The structure of the EBV genome in NPC
      suggests that NPC is a clonal proliferation of epithelial cells which emerges
      after EBV infection. The disease develops with high incidence in specific
      populations in discrete geographic locations, implicating possible genetic or
      environmental cofactors. Mutations of the p53 gene are among the most frequent
      genetic changes found in a large variety of human tumors. Mutations in p53 have
      been shown to abrogate the suppressor function of wild-type p53 and thus
      contribute to the transformed phenotype. To determine if mutation in p53
      participates in the development of the malignant clone in NPC, the structure and
      sequence of p53 in 42 primary, metastatic, and nude mouse-passaged NPC specimens
      was analyzed. A high frequency (6 of 9) of mutations was detected in the nude
      mouse-passaged tumors, while only 2 of 15 metastatic and 0 of the 18 primary
      tumors harbored mutant p53. The p53 mutations included single-point mutations and
      more extensive changes such as frame shifts, deletion, duplication, or complete
      loss of coding sequences. These data indicate that alterations of the p53 gene
      are unlikely to be involved in the initial genetic events leading to the clonal
      outgrowth in NPC. However, although it is a rare NPC which can be established in
      nude mice, this growth advantage appears to be conferred on tumors bearing a
      mutant p53.

PMID- 1349928
TI  - Diagnostic and therapeutic technology assessment. Surrogate markers of
      progressive HIV disease.

PMID- 1349929
TI  - [Studies on the excretion of urinary glycylprolyl dipeptidyl-aminopeptidase (GP
      DAP) during normal pregnancy].
AB  - Several investigators reported that GP-DAP activity, one of dipeptidyl
      aminopeptidases, increased in urine of patients with various renal diseases. In
      this study, we determined urinary GP-DAP and NAG activities of 165 subjects in
      normal pregnant women. It was clear that urinary GP-DAP was increased less than
      NAG with the progress of normal pregnancy. In conclusion, it is suggested that
      urinary GP-DAP may be a better marker than NAG for the discrimination of renal
      diseases from normal pregnancy.

PMID- 1349930
TI  - [Affected siblings with Alzheimer's disease had missense mutation of codon 717 in
      amyloid precursor protein gene].
AB  - Using reverse genetic techniques, the gene responsible for familial Alzheimer's
      disease (FAD) is one of the clues to identify the pathogenesis of Alzheimer's
      disease (AD). Recently a missense mutation in the APP (amyloid precursor protein)
      gene (generally this mutation was called APP717) was detected in 2 Caucasian AD
      families and the same mutation was found in 3 Japanese AD families. We
      experienced brother's cases who were diagnosed as AD. Both of them and one normal
      person of the next generation had APP717. The first symptom of the elder brother
      (case 1) was forgetfulness at 52 years old, then dementia was advanced. In his
      clinical course there were characteristic findings such as the mirror sign,
      pseudodialog and jargon which has been rarely described in the Japanese
      literature. Finally he died of pneumonia at 57 years old. He was diagnosed as AD
      pathologically and physical findings of brain CT, SPECT (single photon emission
      computed tomography) and EEG supported this diagnosis clinically. The first
      symptom of the younger brother (case 2) was also forgetfulness at 45 years old,
      then severe dementia was advanced, at last he died of pneumonia at age 53 old. On
      the other hand the mother of the brothers died of severe dementia, so it was
      suspected that brothers died of severe dementia, so it was suspected that she had
      had AD. The clinical courses and pathological findings were thought to be typical
      of AD, namely there were no significant differences in comparison with other
      cases of FAD and sporadic AD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1349931
TI  - A 75-year-old woman with longstanding hypertension, resulting in congestive heart
      failure and renal failure.

PMID- 1349932
TI  - Genetic profiles of 11 inbred rat strains at 25 biochemical marker loci and five
      RFLP loci.

PMID- 1349933
TI  - Lymphocytotoxic strains of feline leukemia virus induce apoptosis in feline T4
      thymic lymphoma cells.
AB  - Feline leukemia retrovirus (FeLV) strains with subgroup C env genes kill feline
      T4 lymphoma 3201 cells by 7 to 12 days after in vitro inoculation, whereas FeLV
      strains with subgroup A env genes do not. Neither FeLV-A nor FeLV-C kill feline
      fibroblasts. FeLV-C, but not FeLV-A, is replicated to higher titer by 3201 cells
      and productive infection precedes death by 3 to 7 days. Transcriptional activity
      of the FeLV-C long terminal repeat, as assessed by chloramphenicol
      acetyltransferase activity, is high in feline lymphoid cells but low in feline
      fibroblasts. Activity of the FeLV-A long terminal repeat is moderate in both cell
      types. FeLV-C-infected cells form aggregates 1 to 4 days before dying;
      ultrastructurally, virus particles can be seen approximating the clustered cells.
      Dying cells demonstrate nuclear condensation, surface blebbing, and
      fragmentation. DNA fragmentation and laddering compatible with apoptosis occur 1
      to 2 days before massive cell death. In FeLV-C-infected 3201 cells, a shift from
      phospholipid to neutral lipid incorporation of [14C]oleic acid, increases in
      palmitic acid proportions and decreases in linoleic acid proportions occur 1 to 2
      days before peak killing. Exposure of 3201 cells to ultraviolet-inactivated FeLV
      KT (200-800 micrograms/10(6) cells) causes cytostasis within 2 days and death
      within 4 days. Blebbing and nuclear condensation occur but clusters do not form.
      The induction of programmed cell death in feline thymic lymphoma cells by
      subgroup C feline retroviruses may be relevant to the pathogenesis of FeLV
      induced thymic atrophy, paracortical lymphoid depletion and acquired
      immunodeficiency in vivo.

PMID- 1349934
TI  - Age-associated decrease in proportion and antigen expression of CD8+/CD4+
      thymocytes in BALB/c mice.
AB  - We studied the distribution of Thy-1.2+, CD8+ and CD4+ thymocytes in 3-, 6.5-, 12
      and 18-month-old inbred BALB/c mice by staining cells with specific monoclonal
      antibodies (mAb) using indirect membrane immunofluorescence. The percentages of
      Thy-1.2+, CD8+, and CD4+ thymocytes did not vary with age until 12 months, but
      they exhibited at 18 months a highly significant decline. Staining thymocytes
      with mAb CD8 and CD4 alone or in a mixture allowed us to show that the age
      related decline in proportions of CD8+ and CD4+ thymic cells is associated with
      the double positive (CD8+/CD4+, immature) subset. Most importantly, we observed a
      progressive age-related decrease in ratio of bright/dull Thy-1.2+, CD8+ and CD4+
      thymocytes. The CD8+ and CD4+ thymocytes that did not adhere to peanut agglutinin
      (PNA-, which is supposed to represent the mature single positive subset) did not
      show any age-related change in the proportion of bright and dull cells.
      Therefore, we concluded that the double positive (CD8+/CD4+, immature, PNA+)
      thymocytes display reduced expression of CD8 and CD4 antigens with aging. The
      implications of these findings to the fundamental mechanisms of immunosenescence
      are discussed.

PMID- 1349935
TI  - Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis
      in man.
AB  - Animal studies indicate a possible role for lipid oxidation in the development of
      atherosclerosis. We set out to investigate whether there was a relation between
      the ability of low-density lipoprotein (LDL) to resist oxidation in vitro and the
      severity of coronary atherosclerosis in man. 35 unselected young (mean [SD] age
      39.9 [4.2] years) male survivors of myocardial infarction underwent angiography,
      and LDL was isolated from their plasma by density gradient ultracentrifugation.
      In-vitro LDL susceptibility to oxidation was assessed by determination of the lag
      phase for the formation of conjugated dienes in the presence of copper ions. An
      inverse relation was found between lag phase and quantitative estimates of global
      coronary atherosclerosis (r = -0.45; p less than 0.02). Multivariate analysis
      indicated that the lag phase for oxidative modification of LDL and LDL
      cholesterol concentration correlated independently with severity of coronary
      atherosclerosis. The lag phase for oxidation of LDL was also related to the
      triglyceride content of the LDL fraction (r = -0.55; p less than 0.002). The
      finding that susceptibility to LDL oxidation is associated with severity of
      coronary atherosclerosis may indicate that lipid oxidation promotes premature
      coronary atherosclerosis and that individuals with an LDL enriched in
      triglycerides are at particular risk.

PMID- 1349936
TI  - HIV replication during the first weeks of life.
AB  - Diagnosis of HIV infection among children born to HIV-positive mothers can be
      made in the first 12 months, but few studies have examined HIV status during the
      first weeks of life. In a prospective longitudinal study of 50 infants born to
      HIV-1 seropositive women, blood samples were obtained at birth and at 4-9 weeks
      and 5-9 months of age, and were tested for HIV-1 by the polymerase chain reaction
      (PCR), viral culture, and p24 antigen measurements. 16 were diagnosed as HIV
      infected by the age of 4-9 weeks according to both PCR and culture; by contrast,
      infection could be detected in only 5 children at birth. No changes in HIV status
      were observed between 4-9 weeks and 5-9 months in the 44 children who could be
      retested. Perinatal HIV-1 infection can therefore be diagnosed in the first 2
      months of life, either by PCR or viral culture. Our inability to detect HIV-1
      infection at birth in almost 70% of babies subsequently found infected suggests
      an active replication of HIV during the first weeks of life. Our results might
      favour the hypothesis that transmission of HIV-1 takes place either at the end of
      pregnancy or at delivery.

PMID- 1349937
TI  - Efficiency and accuracy of polymerase-chain-reaction assay for cystic fibrosis
      allele delta F508 in single cell.
AB  - Diagnosis of genetic disorders in the embryo before implantation, though possible
      by removal of one or two blastomeres at the eight-cell stage, is still
      experimental because the procedures of gene analysis of DNA from a single cell
      are not yet reliable enough for clinical application. We have evaluated the
      efficiency and accuracy of polymerase-chain-reaction (PCR) amplification of a
      single-copy gene, wild-type or cystic fibrosis delta F508 allele, on single sperm
      cells from a donor known to be a heterozygous carrier of the delta F508 mutation.
      DNA from single spermatozoa was decontaminated by restriction-enzyme treatment,
      then the region around the delta F508 site was amplified by nested PCR. The
      distribution of the wild-type and mutant alleles (59 [55%] and 48 [45%,
      respectively]) in the 107 single spermatozoa did not differ from that expected
      (50% each). 1 sample did not provide an amplified signal. To check that the two
      alleles would be amplified with equal efficiency when they were both present
      within a cell, we did PCR for 51 two-sperm samples. Again the distribution did
      not deviate from that expected (17 [33%] both wild-type; 21 [41%] one wild-type,
      one delta F508; 13 [26%] both delta F508 vs 25%; 50%; 25% expected). None of the
      74 blanks in these experiments was contaminated. We conclude that our delta F508
      single-cell assay is efficient and accurate and can be used for analysis of
      blastomere DNA to diagnose cystic fibrosis before embryo implantation.

PMID- 1349938
TI  - Viruses in idiopathic inflammatory myopathies: absence of candidate viral genomes
      in muscle.
AB  - There is indirect evidence that various viruses have aetiological roles in the
      idiopathic inflammatory myopathies. By means of a sensitive and specific method
      based on the polymerase chain reaction (PCR), we sought direct evidence for the
      presence in affected muscle of nucleic acid sequences from Coxsackie virus, mumps
      virus, encephalomyocarditis virus, adenovirus, human T-lymphotropic virus types I
      and II, and human immunodeficiency virus. RNA was extracted from muscle biopsy
      samples obtained from 44 patients with idiopathic inflammatory myopathies a mean
      of 45 (range 0-216) months after disease onset. All the subjects were older than
      16 years at disease onset. The integrity of the mRNA extracted was confirmed by
      the successful PCR amplification of insulin receptor mRNA in all samples. The PCR
      method was able to detect between 1 and 20 molecules of added viral nucleic acid
      for the picornaviruses sought. No detectable virus sequences were found, however,
      in any of the patients' muscle samples or in samples from 13 controls. We tested
      for retroviral DNA in 22 samples (17 patients, 5 controls) that met our criterion
      for adequate DNA extraction (detectable beta-actin DNA by PCR); again no virus
      sequences were found. Persistence in muscle of these or closely related viruses
      is unlikely to be a continuing stimulus for disease in the idiopathic
      inflammatory myopathies.

PMID- 1349939
TI  - Response of refractory Hodgkin's disease to monoclonal anti-CD30 immunotoxin.
AB  - In Hodgkin's disease, Hodgkin and Reed-Sternberg cells consistently express the
      antigen CD30. We investigated the possible therapeutic role of an immunotoxin
      prepared by covalent linking of an anti-CD30 monoclonal antibody (Ber-H2) to
      saporin (SO6), a type-1 ribosome-inactivating protein. The immunotoxin (0.8 mg/kg
      in one or two doses) was given to four patients with advanced refractory
      Hodgkin's disease. In three, there was rapid and substantial reduction in tumour
      mass (50% to greater than 75%). Clinical responses were transient (6-10 weeks).
      In-vivo binding of the immunotoxin to tumour cells was shown by immunohistology
      in two patients. Antibodies to both parts of the immunotoxin developed in all
      patients.

PMID- 1349940
TI  - Guidelines for doctors in the New World.

PMID- 1349941
TI  - Hepatitis A: a vaccine at last.

PMID- 1349942
TI  - Protease inhibitors for delayed cerebral ischemia after subarachnoid haemorrhage?

PMID- 1349943
TI  - Chlamydia and complexes.

PMID- 1349944
TI  - Migraine: theories of pathogenesis.

PMID- 1349945
TI  - Treatment of migraine.

PMID- 1349946
TI  - Population screening for fragile X.
AB  - A screening programme to detect fragile X syndrome has been operating in New
      South Wales, Australia, since 1984. The aim of this programme is to find
      previously unidentified individuals with the syndrome so that their extended
      families can be properly informed of the risks before making decisions about
      childbearing. 14,225 individuals attending adult and child facilities for the
      intellectually handicapped have been screened, of whom 8172 have been offered
      testing for the fragile X syndrome with a 79% uptake of the service. 253 probands
      were found, and in the extended families 818 females at 25-100% risk of being
      carriers were interviewed and counselled. Continuing contact was maintained and
      prenatal diagnosis was offered. The effect of the programme was assessed in a
      subgroup of 90 individuals, most of whom were appreciative of the service and
      felt that they had been adequately informed. The influence of knowing the
      diagnosis and its genetic implications were also assessed, the main consequences
      being a 26% reduction in births and a 61% uptake of prenatal diagnosis. Improved
      techniques for diagnosis of fragile X have benefited the families identified and
      counselled, suggesting that systematic screening for fragile X should be an
      essential component of community genetic services.

PMID- 1349947
TI  - Micronutrient deficiencies in refugees.

PMID- 1349948
TI  - European boards and colleges: europaeds or urophobia?

PMID- 1349949
TI  - WHO: helping hand for women.

PMID- 1349950
TI  - After ISIS-3.

PMID- 1349951
TI  - After ISIS-3.

PMID- 1349952
TI  - After ISIS-3.

PMID- 1349953
TI  - Imprinting and Beckwith-Wiedemann syndrome.

PMID- 1349954
TI  - Octreotide.

PMID- 1349955
TI  - Psychogenic vomiting.

PMID- 1349956
TI  - Dipyridamole.

PMID- 1349957
TI  - Oral water intoxication in babies.

PMID- 1349958
TI  - Multifocal cerebral gliomas associated with secondary malignancies.

PMID- 1349959
TI  - Binocular amblyopia improved by yellow spectacles.

PMID- 1349961
TI  - Testing histologically negative lymph nodes for papillomavirus when evaluating
      metastasis in cervical cancer.

PMID- 1349960
TI  - HPV-16 and cervical intraepithelial neoplasia.

PMID- 1349962
TI  - Anaphylactoid response to intravenous acetylcysteine.

PMID- 1349963
TI  - Omental milky spots and the local immune response.

PMID- 1349964
TI  - Erythrocyte membrane docosahexaenoic acid in haemodialysis patients on epoetin.

PMID- 1349966
TI  - Spain's health care.

PMID- 1349967
TI  - Time out for TNM.

PMID- 1349965
TI  - Dietary phyto-oestrogens and the menopause in Japan.

PMID- 1349968
TI  - Ethics and clinical research in obstetric anaesthesia.

PMID- 1349969
TI  - Aluminium and dementia.

PMID- 1349970
TI  - Clinical management of trisomy 18.

PMID- 1349971
TI  - Surgical careers and female students.

PMID- 1349972
TI  - Aluminium and dementia.

PMID- 1349973
TI  - BCG vaccine and leprosy.

PMID- 1349974
TI  - Children with persistent diarrhoea.

PMID- 1349975
TI  - Outpatient treatment of Hickman catheter infections.

PMID- 1349976
TI  - Lyme cystitis and neurogenic bladder dysfunction.

PMID- 1349978
TI  - Intravesical capsaicin for neurogenic bladder dysfunction.

PMID- 1349977
TI  - Tests for renovascular disease.

PMID- 1349979
TI  - All-trans retinoic acid and side-effects.

PMID- 1349980
TI  - N-methyl-D-aspartate binding sites in neonatal and adult brain.

PMID- 1349981
TI  - Coronary atheroma regression trials.

PMID- 1349982
TI  - Coronary atheroma regression trials.

PMID- 1349984
TI  - Coronary atheroma regression trials.

PMID- 1349983
TI  - Coronary atheroma regression trials. MAAS Steering Committee.

PMID- 1349985
TI  - Arginine derivatives and uraemia.

PMID- 1349986
TI  - Coronary atheroma regression trials.

PMID- 1349987
TI  - Increased plasma fibronectin in Werner syndrome.

PMID- 1349988
TI  - Retraction: evidence for genetic HIV variants from detection of HIV-DNA.

PMID- 1349989
TI  - Linkage of type 2 diabetes to the glucokinase gene.
AB  - Maturity-onset diabetes of the young (MODY) is a subtype of type 2 diabetes that
      presents from the second decade and has an autosomal dominant mode of
      inheritance. We have investigated the glucokinase gene, a candidate gene for
      diabetes, in two MODY pedigrees. In a large 5-generation pedigree (BX) with 15
      diabetic members, use of a microsatellite polymorphism revealed linkage of
      diabetes to the glucokinase locus on chromosome 7p. A peak lod score of 4.60 was
      obtained at a recombination fraction (theta) of zero. This finding suggests that
      a defective glucokinase gene contributes to the diabetes phenotype in this
      pedigree. This is not universal in MODY since linkage to the glucokinase locus
      was excluded in a second pedigree M (lod score = -7.36 at theta = 0). The
      affected members in pedigree BX were diagnosed either when young (in pregnancy or
      on screening) or when they presented symptomatically in middle and old age; most
      of them were treated by diet alone. Defects in the glucokinase gene may play an
      important part in the pathogenesis of type 2 diabetes.

PMID- 1349990
TI  - Early intervention in psychiatric emergencies: a controlled clinical trial.
AB  - In the UK, psychiatric care of patients with acute and chronic disorders has
      increasingly moved from hospital to the community. We have evaluated in a
      controlled trial patients with severe mental illness, who were assigned to early
      intervention by community services or to standard hospital treatment. 100
      patients aged 16 to 65 years presenting as psychiatric emergencies to an inner
      London teaching hospital were randomly allocated to a multidisciplinary community
      based team (n = 48) or conventional hospital-based psychiatric services (n = 52)
      and assessed over a 3-month period. Ratings of psychopathology and social
      functioning were made before treatment and after 2, 4, and 12 weeks by
      independent assessors. 85 patients completed all assessments, and all patients
      had evaluable data beyond 2 weeks. 3 patients died during the study, 2 from
      natural causes and 1 from an accident. Patients referred to the community service
      showed greater improvement in symptoms and were more satisfied with services than
      those in the hospital-based service. Patients treated in the hospital-based
      service spent eight times as many days as psychiatric inpatients as those treated
      in the community-based service. Patients both prefer and seem to benefit from
      community-based psychiatric care, and our early-intervention community service
      might be a good model for such care.

PMID- 1349991
TI  - Pickled vegetables in the aetiology of oesophageal cancer in Hong Kong Chinese.
AB  - Oesophageal cancer is common in Chinese populations, but individual-based
      epidemiological studies have provided little explanation. A case control study
      with 400 cases and 1598 controls (800 hospital and 798 general practice) was
      conducted among Hong Kong Chinese. In multivariate analyses, statistically
      significant effects on risk were detected for several potentially preventable
      exposures with high attributable risks (ARs). These included preference for
      consuming drinks or soups at high temperature (AR = 14%), infrequent consumption
      of green leafy vegetables (AR = 15%) and citrus fruits (AR = 26%), ingestion of
      pickled vegetables (AR = 29%), tobacco smoking (AR = 44%), and alcohol drinking
      (AR = 48%). On the assumption of multiplicative risk, the combined AR due to
      these exposures was 89%. This is the first case control study to show an
      association between pickled vegetable consumption and oesophageal cancer risk.
      The finding considerably strengthens the evidence for carcinogenicity of N
      nitroso compounds in man and helps to explain the very high risk among Chinese.

PMID- 1349992
TI  - Effects of dual-chamber pacing in hypertrophic obstructive cardiomyopathy.
AB  - Although attempts have been made to treat hypertrophic obstructive cardiomyopathy
      with right ventricular pacing, the usual treatment for those refractory to
      medical therapy is open heart surgery. To assess in detail the value of non
      surgical therapy the effects of acute and long-term dual-chamber pacing were
      investigated in 13 patients with hypertrophic obstructive cardiomyopathy
      refractory to medical treatment. In the first part of the study, atrioventricular
      (AV) sequential pacing was found to reduce peak subaortic pressure gradient in 12
      of the 13 patients, from 82 (SD 42) to 47 (34) mm Hg (p less than 0.002), without
      concomitantly reducing aortic blood pressure or cardiac output. This effect was
      related to AV interval. In the second part of the study, a dual-chamber pacemaker
      was implanted in 8 patients and programmed to the optimum AV interval for the
      individual (50-90 ms). Patients were followed up for up to 62 months. Pacing
      resulted in a significant and long-lasting reduction in severity of angina
      pectoris (from NYHA class 3 to 1) and dyspnoea (from NYHA class 3 to 2).
      Echocardiography showed no significant change in septal thickness or left
      ventricular contractility but there was a trend to a spontaneous decrease in
      obstruction. In patients with hypertrophic obstructive cardiomyopathy,
      synchronised and ventricular pacing at optimum AV interval for the individual
      reduces the intraventricular pressure gradient and improves functional tolerance.
      Since the effect is longlasting, such pacing should be deemed an alternative
      therapy to surgery in selected cases.

PMID- 1349994
TI  - Earth matters.

PMID- 1349993
TI  - Abnormalities of surfactant in children with recurrent cyanotic episodes.
AB  - The mechanism of recurrent cyanotic episodes in infants and children is not
      known, but a deficiency of surfactant is a possible cause. We have measured the
      amount of surfactant collected by bronchoalveolar lavage from two children with
      recurrent cyanotic episodes and from two controls with anatomical airway
      obstructions. We also assessed the physical properties of the surfactant by
      changing the surface area (A) of a monolayer and measuring its surface tension
      (gamma). The cases had lower amounts of surfactant extracted, which could explain
      some of the abnormalities of the gamma/A loops. However, the finding that the
      cases had reversed loops (ie, the surface tension is higher during monolayer
      compression than during expansion) shows that there is also a qualitative
      abnormality. These features suggest a possible diagnostic test if not a mechanism
      for this disorder.

PMID- 1349995
TI  - Microdialysis.

PMID- 1349996
TI  - Fish oils in pregnancy.

PMID- 1349997
TI  - Congenital bilateral absence of the vas deferens and cystic fibrosis.

PMID- 1349998
TI  - What are the forests worth?

PMID- 1349999
TI  - Shockwave lithotripsy of salivary duct stones.
AB  - Surgical extirpation of the affected gland has been necessary for cases of
      sialolithiasis in which the stone cannot be removed by dilatation or dissection
      of the salivary duct. The ability of the piezoelectric lithotripter to deliver
      shockwaves to a small focus makes extracorporeal shockwave lithotripsy of
      salivary gland stones potentially safe. Its safety and efficacy have been
      assessed in 51 patients with symptomatic solitary salivary stones that could not
      be removed by conservative measures. The stones had a median diameter of 8 (range
      4-18) mm and were located in the submandibular gland in 69% of patients and in
      the parotid gland in 31%. A total of 72 shockwave treatment sessions (maximum 3
      per patient) were given under continuous sonographic monitoring. In 45 patients
      (88%) complete fragmentation (fragments less than or equal to 3 mm) of the
      concrements was achieved. No patient needed anaesthesia, sedatives, or
      analgesics. The only untoward effects were localised petechial haemorrhages after
      10 (13%) out of 72 treatments and transient swelling of the gland immediately
      after delivery of shockwave in 2/72 (3%) sessions. 20 weeks after the first
      session 90% (46/51) of patients were free of discomfort, and 53% (27/51) were
      stone free. Stone-clearance rate was higher among patients with stones in the
      parotid gland (81%) than among those with stones of the submandibular gland
      (40%). Auxiliary measures such as dilatation or dissection of the salivary duct
      were required only in patients with stones in the submandibular gland (20%). No
      long-term damage to the treated salivary gland or to adjacent tissue structures
      was noted during the median follow-up of 9 (1-24) months. Extracorporeal
      piezoelectric shockwave therapy seems likely to be safe, comfortable, and
      effective minimally-invasive, non-surgical treatment for salivary stones.

PMID- 1350000
TI  - Value of the alert and action lines on the partogram.
AB  - A partogram based on a World Health Organisation model has been used for many
      years in the peripheral maternity clinics of Pikine, Senegal, to monitor labour.
      We have assessed the value of the partogram and efficacy of the alert and action
      lines. 1022 pregnant women were monitored by partogram during 4 months. The alert
      line was crossed in 100 (9.8%) of these cases and the frequency of neonatal
      resuscitation was higher for this group (relative risk 4.0, 95% confidence
      interval 2.3-7.1; p less than 0.0001), as was the number of "fresh" stillbirths
      (5.3, 1.8-15.6; p less than 0.01) (recent death may have occurred during labour).
      Among the women who crossed the alert but not the action line, neonatal
      resuscitation was also four times more likely than for the normal labour group
      (4.0, 2.1-7.6; p less than 0.001), and the fresh stillbirth rate was higher but
      not significantly so. For women who crossed both lines, the fresh stillbirth rate
      was ten times higher than for women in the normal labour group (9.9, 2.8-34.7; p
      less than 0.001). Crossing the alert line had a sensitivity of 27%, a specificity
      of 93%, and a positive predictive value of 17% for neonatal resuscitation. If the
      action line was chosen as the decision level, the positive predictive value
      remained the same but the sensitivity was only 8%. Health workers intervened (eg,
      artificial rupture of the membranes, administration of oxytocics) in half the
      dystocic cases. Of the women who did not receive any such treatment 44% crossed
      the action line compared with only 26% of those who did receive treatment (p =
      0.06). The results show the usefulness and efficacy of the partogram and
      underscore the value of medical intervention as soon as the alert line is
      crossed.

PMID- 1350001
TI  - Growth factors and racial differences in severity of hypertension and renal
      diseases.

PMID- 1350003
TI  - Health carers, patients, and HIV.

PMID- 1350002
TI  - Time for the Vatican to bend.

PMID- 1350004
TI  - Papillomaviruses, p53, and cervical cancer.

PMID- 1350005
TI  - Papillomaviruses, p53, and cervical cancer.

PMID- 1350006
TI  - Papillomaviruses, p53, and cervical cancer.

PMID- 1350007
TI  - Local anaesthetic creams and intradermal skin tests.

PMID- 1350008
TI  - HPV16 DNA and prediction of high-grade CIN.

PMID- 1350009
TI  - HPV16 DNA and prediction of high-grade CIN.

PMID- 1350010
TI  - Combined chemotherapy versus melphalan and prednisolone for treatment of
      myelomatosis.

PMID- 1350011
TI  - QBC malaria diagnosis.

PMID- 1350012
TI  - QBC malaria diagnosis.

PMID- 1350013
TI  - Do women benefit more than men from post-MI beta-blockade?

PMID- 1350014
TI  - Diphtheria, pertussis, and tetanus vaccination.

PMID- 1350015
TI  - Diphtheria, pertussis, and tetanus vaccination.

PMID- 1350016
TI  - Routine examination of children at risk of autosomal dominant polycystic kidney
      disease.

PMID- 1350017
TI  - Asthma and wheezing.

PMID- 1350018
TI  - Asthma and wheezing.

PMID- 1350019
TI  - Echinococcal infection in a Ghanaian patient.

PMID- 1350020
TI  - Cattle strain of Echinococcus granulosus and human infection.

PMID- 1350021
TI  - Invasive infection with non-toxigenic Corynebacterium diphtheriae among drug
      users.

PMID- 1350022
TI  - Prenatal exclusion of severe factor VII deficiency by DNA sequencing.

PMID- 1350024
TI  - Staging of breast cancer.

PMID- 1350023
TI  - Staging of breast cancer.

PMID- 1350025
TI  - EC proposal for in-vitro diagnostic medical devices Directive.

PMID- 1350026
TI  - Nursing's identity crisis.

PMID- 1350027
TI  - Surgical careers and female students.

PMID- 1350028
TI  - Prenatal diagnosis of haemoglobinopathies in Sicily.

PMID- 1350029
TI  - Leeches and hepatitis B.

PMID- 1350030
TI  - Thalidomide: a restricted role.

PMID- 1350031
TI  - Thalidomide: a restricted role.

PMID- 1350032
TI  - Fatal myocardial infarction and Tyrolean winds (the Foehn)

PMID- 1350033
TI  - Correct use of laparoscopic insufflator.

PMID- 1350034
TI  - New mosquito in Africa.

PMID- 1350035
TI  - Thromboembolic complications and dose of monoclonal OKT3 antibody.

PMID- 1350036
TI  - Housedust mite allergens and IgG.

PMID- 1350037
TI  - Are health-care workers really at risk of HCV infection?

PMID- 1350038
TI  - Endocrine effects of sumatriptan.

PMID- 1350039
TI  - Implants and breast cancer.

PMID- 1350041
TI  - Side-effects, structure, and H2-receptor antagonists.

PMID- 1350040
TI  - Antineuronal antibodies and subacute paraneoplastic neuropathy.

PMID- 1350042
TI  - Urapidil and enuresis.

PMID- 1350043
TI  - [Drug therapy of chronic inflammatory bowel disease--reliable standards and new
      developments].
AB  - The standard therapy of ulcerative colitis and Crohn's disease is based on the
      treatment with corticosteroids, sulfasalazine and 5-aminosalicylic acid
      (mesalazine). Depending on the localization and the extent of bowel inflammation
      these drugs are given topically (proctosigmoiditis, left-side colitis) or
      systemically (total and subtotal colitis). Azathioprin and metronidazole are
      considered to be reserve drugs (the latter one having proven to be effective only
      in Crohn's disease). During the last years, the efficacy of several new agents
      has been investigated. At present, their routine administration cannot be
      advised. The clinical usefulness of new topical corticosteroids showing both high
      antiinflammatory effect and no or at least minor systemic side effects is
      promising.

PMID- 1350044
TI  - Construction and analysis of Bordetella pertussis mutants defective in the
      production of fimbriae.
AB  - Although the role of fimbriae in bacterial disease has been well established,
      little is known about the function of Bordetella pertussis fimbriae. To study
      this function, well-defined fimbrial mutants were constructed. B. pertussis
      harbours three fimbrial genes, fim2, fim3 and fimX, and strains were constructed
      in which one or more fimbrial genes were inactivated by means of gene
      replacement. Analysis of these strains by means of immunoblotting suggested the
      presence of a fourth fimbrial gene, tentatively designated fimY. A fimbrial
      mutant was analysed in a mouse respiratory infection model, together with a
      strain harbouring a deletion in the gene for the filamentous haemagglutinin. Both
      mutants were affected in their ability to persist in the trachea. Persistence in
      the nasopharynx was only affected by the mutation in the filamentous
      haemagglutinin gene. Neither the filamentous haemagglutinin nor the fimbrial
      mutants were affected in their ability to persist in the lung. Our results
      suggest that the filamentous haemagglutinin plays a more crucial role than
      fimbriae in the colonization of the upper respiratory tract of the mouse.

PMID- 1350045
TI  - Comparative efficacy of autolysin and pneumolysin as immunogens protecting mice
      against infection by Streptococcus pneumoniae.
AB  - Previous studies on Streptococcus pneumoniae have established that the
      pneumococcal proteins autolysin (N-acetylmuramyl-L-alanine amidase) and
      pneumolysin both contribute significantly to the virulence of the organism. In
      the present work, autolysin and a defined toxoid derivative of pneumolysin were
      tested, individually and in combination, for efficacy in a mouse model as
      antigens protecting against challenge with virulent, wild-type S. pneumoniae.
      While each antigen alone provided significant protection, the degree of
      protection was not increased when the antigens were administered together. In an
      additional experiment, mice were challenged with a genetically-modified mutant
      strain of pneumococcus unable to express active pneumolysin. Pre-immunization of
      such mice with autolysin failed to provide any significant protection against the
      challenge. The results of this study suggest that the most important contribution
      made by autolysin to the virulence of S. pneumoniae may be its role in mediating
      the release of pneumolysin from the pneumococcal cytoplasm during infection.

PMID- 1350047
TI  - Geographic mitochondrial DNA variation in the rock hyrax, Procavia capensis.
AB  - Restriction-fragment-length polymorphisms in mitochondrial DNA (mtDNA) were used
      to evaluate geographic population genetic structure in the rock hyrax, Procavia
      capensis, a species which occurs widely, though restricted to rocky habitat,
      throughout South Africa. Ten restriction endonucleases were employed to assay
      mtDNAs from 55 specimens representing 10 localities. Haplotypes showed strong
      geographic patterning, and estimates of nucleotide sequence divergence indicate
      two major clades thought to be dispersing along separate routes. The divergence
      time of approximately 2 Myr between clades is relatively high for intraspecific
      variation. We speculate that the marked genetic break distinguishing the
      northwestern populations from those constituting the south/central clade may be
      indicative of two species in what has conventionally been regarded as P.
      capensis.

PMID- 1350046
TI  - Effect of insertional inactivation of the genes encoding pneumolysin and
      autolysin on the virulence of Streptococcus pneumoniae type 3.
AB  - Derivatives of Streptococcus pneumoniae type 3 deficient in production of either
      pneumolysin or autolysin were constructed. This was achieved by transformation of
      type 3 pneumococci with DNA from derivatives of a rough strain (Rx1), in which
      the respective genes had been interrupted by insertion-duplication mutagenesis
      using internal fragments of the cloned genes in the vector pVA891. Southern blot
      analysis confirmed that the pneumolysin or autolysin genes in the respective
      transformants had been interrupted by insertion of the plasmid-derived sequences.
      Both the pneumolysin-negative and the autolysin-negative strains had
      significantly reduced (P less than 0.0001) virulence in mice, as judged by
      survival time after intraperitoneal challenge. The median survival time of mice
      challenged with type 3 pneumococci in which either pneumolysin or autolysin
      production had been reconstituted by back-transformation of the mutants with an
      intact copy of the respective cloned gene (with concomitant elimination of
      plasmid-derived sequences), was indistinguishable from that of mice challenged
      with the wild-type strain. These results establish the importance of both
      pneumolysin and autolysin to the virulence of type 3 pneumococci.

PMID- 1350048
TI  - The role of pili in colonization of the rabbit intestine by Vibrio
      parahaemolyticus Na2.
AB  - Vibrio parahaemolyticus Na2 and its pili were studied in relation to intestinal
      colonization. The isolated pili were adhesive to the intestinal epithelium. The
      adhesion of the organisms was blocked by masking the epithelial receptor with the
      purified pili, or by treating the organisms with anti-pilus antibody (Fab
      fraction). These results suggest that the pili of V. parahaemolyticus Na2 play an
      important role in the adhesion of the organisms to the rabbit intestine.

PMID- 1350049
TI  - Proposal for clinical trials using anti-inflammatory drugs in the therapy of
      angina pectoris, myocardial infarction and coronary restenosis after angioplasty
      and bypass grafting.
AB  - The importance of inflammatory phenomena in atherosclerosis is now appreciated.
      Here, a clinical trial to be conducted using anti-inflammatory drugs
      (sulfasalazine, griseofulvin and colchicine) in angina pectoris, myocardial
      infarction and coronary restenosis after angioplasty and bypass grafting is
      proposed. Patients who have both atherosclerosis and a disease responsive to anti
      inflammatory drugs (ulcerative colitis or Crohn's disease, dermatomycosis,
      necrotizing vasculitis, Behcet's disease, gout or other colchicine-sensitive
      diseases), are desirable targets of the present proposal.

PMID- 1350050
TI  - Alzheimer's disease: a 'cobalaminergic' hypothesis.
AB  - An association between Alzheimer's Disease (AD) and low CSF and serum vitamin B12
      (B12) has recently been described (1, 2, 3). This is apparently independent of
      nutritional intake (4). It has been suggested that such patients may exhibit an
      atypical form of cobalamin deficiency (3, 4). It is therefore proposed that these
      deficiencies may be aetiologically important, at least in sub-groups of AD, and a
      mechanism is described whereby B12 deficiency may result in the characteristic
      neurotransmitter changes of the disease. The hypothesis generates predictions
      regarding biochemical evaluation of such patients and suggests associations
      between the neurochemical disturbances and structural abnormalities of AD.

PMID- 1350051
TI  - Molecular neuroanatomic mechanisms of Parkinson's disease: a proposed therapeutic
      approach.
AB  - Current concepts suggest that parkinsonian bradykinesia is a consequence of an
      imbalance between striatopallidal and striatonigral output pathways. Dopamine
      appears to oppositely effect these neurons due to the selective localization of
      the D1 receptor on striatonigral neurons and the D2 receptor on striatopallidal
      neurons. Studies measuring changes in gene regulation suggest how selective D1
      and D2 dopamine agonist treatments may be used to restore the normal balance
      between the striatal output pathways.

PMID- 1350052
TI  - Dopaminergic agonists in the treatment of Parkinson's disease.
AB  - Dopaminergic agonists are drugs that directly stimulate the dopamine receptors of
      the striatum and have proved useful in treating Parkinson's disease. In the
      United States, they are primarily used in conjunction with levodopa. Most have
      long half-lives and have been particularly useful in controlling and attempting
      to prevent motor fluctuations.

PMID- 1350053
TI  - An integrated approach to patient management in Parkinson's disease.
AB  - New concepts about the pathogenesis and pathophysiology of Parkinson's disease
      have emerged. For these concepts to be useful, they must be understood, and for
      them to be applied, the psychology of the patient and the patient's family must
      be understood. The initial consultation is crucial in establishing a successful
      relationship between a patient, family, and physician. This consultation is
      analyzed and ways of avoiding errors and misconceptions delineated. Emphasis is
      placed on imaginitive questioning using the format of the ADL portion of the
      UPDRS in establishing the diagnosis and following treatment. The rational for
      starting treatment with selegiline at this time is discussed in the context of
      the role that increased MAO-B activity plays in the progression of Parkinson's
      disease. After making the diagnosis and starting treatment with selegiline,
      deciding when to start levodopa is the next crucial decision. Often as important
      as deciding when to start levodopa is overcoming the resistance of the patient to
      accept this treatment. The next crucial decision occurs after the patient
      develops response fluctuations on levodopa. A format for assessing the
      fluctuations is presented, and the merits of different treatments, including
      selegiline, dopamine agonists (bromocriptine and pergolide), and sustained
      release or controlled-release levodopa preparations (Sinemet CR), discussed. The
      management of patients with depression, sleep problems, and advanced disease
      including postural instability and mental changes are reviewed.

PMID- 1350054
TI  - Protein kinase-C activation increases the quantity and poly(A) tail length of
      corticotropin-releasing hormone messenger RNA in NPLC cells.
AB  - We have studied the effect of protein kinase-C activation on the regulation of
      CRH gene expression in the human hepatoma cell line NPLC/PRF/5 (NPLC), the only
      cell line known to express the endogenous CRH gene. Incubation of NPLC cells with
      100 nM 12-O-tetradecanoyl phorbol 13-acetate (TPA), a phorbol ester that
      activates protein kinase-C, resulted in a rapid (1-h) and prolonged (72-h)
      increase in CRH mRNA levels, with the maximum increase of 16-fold observed at 24
      h. In addition, TPA treatment increased the size of CRH mRNA by approximately 100
      nucleotides. This size increase, which was blocked by protein synthesis
      inhibitors, occurred within 1 h of TPA addition and lasted at least 8 h, with a
      return toward the baseline size by 24 h. Structural analysis of CRH mRNA revealed
      two poly(A) addition sites and, as found in human placenta, multiple
      transcription start sites. The increase in CRH mRNA size was not due to changes
      in the sites of either transcription initiation or poly(A) addition, but, rather,
      to a 3-fold increase in the length of the poly(A) tail itself. The ability of TPA
      to increase CRH mRNA levels in NPLC cells suggests that the protein kinase-C
      second messenger pathway may be involved in the physiological regulation of CRH
      gene expression. Increases in CRH mRNA poly(A) tail length potentially may
      influence CRH mRNA stability or translatability and, thus, may represent a
      general mechanism by which the protein kinase-C pathway can influence gene
      expression.

PMID- 1350055
TI  - Phylogenetic specificity of prolactin gene expression with conservation of Pit-1
      function.
AB  - In mammals, the pituitary POU homeodomain protein, Pit-1, binds to proximal and
      distal 5'-flanking sequences of the PRL gene that dictate tissue-specific
      expression. These DNA sequences are highly conserved among mammals but are
      dramatically different from PRL 5' sequences in the teleost species, Oncorhynchus
      tschawytscha (chinook salmon). To analyze the molecular basis for pituitary
      specific gene expression in a distantly related vertebrate, we transfected CAT
      reporter gene constructs containing 2.4 kilobases (kb) 5'-flanking sequence from
      the salmon PRL (sPRL) gene into various cell types. Expression of the sPRL gene
      was restricted to pituitary cells, but in rat pituitary GH4 cells levels of
      expression were at least 90-fold lower than those obtained with a -3 kb rat PRL
      (rPRL) construct. Conversely, in primary teleost pituitary cells, -2.4 kb
      sPRL/CAT was expressed at levels about 10-fold higher than -3 kb rPRL/CAT. To
      determine whether species-specific transactivation by Pit-1 was sufficient to
      explain these species differences in PRL gene expression, we isolated a cDNA
      clone encoding the salmon Pit-1 POU domain and constructed a rat Pit-1 expression
      vector that contained salmon Pit-1 POU domain sequences substituted in frame. The
      chimeric Pit-1 encoded 14 amino acids unique to salmon. Coexpression of rat Pit-1
      with salmon or rat PRL/CAT in transfected HeLa cells resulted in specific and
      strikingly comparable levels of promoter activation. Moreover, the specificity
      and efficacy of the chimeric salmon/rat Pit-1 was similar to wild type rat Pit-1
      in activating salmon and rat PRL/CAT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350056
TI  - Inhibition of tyrosine aminotransferase gene expression by retinoic acid.
AB  - Regulation of tyrosine aminotransferase (TAT) gene expression was examined in
      RALA255-10G, a simian virus-40 tsA mutant-immortalized adult rat hepatocyte line.
      At the nonpermissive temperature (40 C), these hepatocytes exhibited a
      differentiated phenotype and actively expressed the TAT gene, but only in the
      presence of dexamethasone (DEX). The glucocorticoid-mediated TAT expression was
      inhibited by cycloheximide, a protein synthesis inhibitor, and by RU486, a
      glucocorticoid antagonist, suggesting that glucocorticoid induction requires
      protein synthesis and may be mediated through hormone receptors. (Bu)2cAMP
      (Bt2cAMP) or retinoic acid, individually or in combination, failed to increase
      TAT mRNA levels. However, Bt2cAMP greatly potentiated the induction by DEX,
      whereas retinoic acid inhibited the induction by DEX or DEX/Bt2cAMP. Nuclear run
      on assays demonstrated that the induction of TAT expression by DEX or DEX/Bt2cAMP
      in RALA255-10G cells is regulated primarily at the transcriptional level. In
      contrast, retinoic acid antagonized the DEX- or DEX/Bt2cAMP-mediated induction
      without affecting the rate of TAT gene transcription. Instead, retinoic acid
      destabilized TAT mRNA. The half-life values of TAT mRNA in DEX/Bt2cAMP- and
      DEX/Bt2cAMP/retinoic acid-treated cells were approximately 235-270 min and 90-100
      min, respectively. Our results indicate that inhibition of TAT expression by
      retinoic acid was regulated primarily at the posttranscriptional level.

PMID- 1350057
TI  - A dominant repressor of cyclic adenosine 3',5'-monophosphate (cAMP)-regulated
      enhancer-binding protein activity inhibits the cAMP-mediated induction of the
      somatostatin promoter in vivo.
AB  - The transactivation of genes through the cAMP-regulated enhancer (CRE) is
      proposed to occur by the binding and phosphorylation of the transcription factor
      CREB (CRE-binding protein). Originally believed to be a single protein, more than
      10 different CREB proteins have been cloned. The contributions of each of these
      factors to gene regulation have yet to be determined unambiguously. We have
      isolated a CREB cDNA that contains a mutation of a single amino acid in the DNA
      binding domain. In gel shift assays, this mutant, designated KCREB, is unable to
      bind to the somatostatin (SS) CRE. In addition, KCREB acts as a dominant
      repressor of the wild-type factor, blocking the ability of wild-type CREB to bind
      to the CRE when present as a KCREB:CREB heterodimer. The KCREB mutant also acts
      as a dominant repressor in vivo, completely blocking the ability of wild-type
      CREB to mediate induction by protein kinase-A of a SS CRE reporter gene in F9
      teratocarcinoma cells. We have used this mutant to analyze the participation of
      CREB in the induction of the SS promoter in CA-77 cells, a medullary thyroid
      carcinoma cell line that produces high levels of SS. Although KCREB can block a
      portion of the cAMP induction of the SS promoter in CA-77 cells, approximately
      45% of the induction remains insensitive to the mutant. These data support the
      paradigm that CREB is involved in the cAMP induction of SS in vivo. Furthermore,
      the inability of KCREB to completely block cAMP-mediated SS expression in CA-77
      cells suggests that additional factors may contribute to the cAMP regulation of
      CRE function.

PMID- 1350059
TI  - Clozapine prevents recurrence of psychosis in Parkinson's disease.
AB  - Psychosis secondary to dopaminergic therapy can limit the ability to manage motor
      symptoms of advanced Parkinson's disease (PD). We report the results of an open
      label 3-month trial that evaluated the antipsychotic effects of clozapine in
      eight PD patients with drug-induced psychosis. Response was quantified using a
      simplified brief psychiatric rating scale and two PD scales. Clozapine
      significantly improved psychiatric scores at low doses. The use of every other
      day regimens (not previously utilized) led to good control of symptoms and
      minimized side effects. Clozapine also had a positive sleep effect in four
      patients and improved dyskinesia in one. Finally, this treatment prevented
      recurrence of psychosis while levodopa doses were significantly increased and
      while other antiparkinsonian medications were added. Motor disability related to
      PD improved as a result of these treatment adjustments. We conclude that
      clozapine is effective in treating drug-induced psychosis in PD and allows for
      safe optimization of antiparkinsonian therapy.

PMID- 1350058
TI  - Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological
      classification.
AB  - Levodopa-induced dyskinesias (LID) in Parkinson's disease (PD) may be classified
      into three main categories: "On" dyskinesias, diphasic dyskinesias (DD), and
      "off" periods. The study of 168 parkinsonian patients showed that about half (n =
      84) showed one pattern of LID only. A combination of two was present in 68, and
      16 had the three presentation patterns. A fairly good correlation between type of
      dyskinesia and presentation pattern was established. Chorea, myoclonus, and
      dystonic movements occurred during the "on" period. Dystonic postures,
      particularly affecting the feet, were mainly present in the "off" period, but a
      few patients had a diphasic presentation. Repetitive stereotyped movements of the
      lower limbs always corresponded to DD. Acute pharmacological tests using dopamine
      agonists (subcutaneous apomorphine 3-8 mg; intravenous lisuride 0.1-0.15 mg) and
      dopamine antagonists (intravenous sulpiride 200-400 mg and intravenous
      chlorpromazine 25 mg) were performed in 40 patients. Dopamine agonists enhanced
      "on" dyskinesias and markedly reduced or abolished "off" period dystonia and DD.
      Dopamine antagonists reduced all types of LID but usually aggravated
      parkinsonism. These clinical and pharmacological results indicate that LID in PD
      are a heterogeneous phenomenon difficult to explain on the basis of a single
      pathophysiological mechanism.

PMID- 1350060
TI  - Ethosuximide and tremor in Parkinson's disease: a pilot study.
AB  - Following the demonstration of an anti-tremor effect of ethosuximide in the 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model, we have tested
      the effect of this drug in 10 patients with typical parkinsonian tremor. Six
      patients suffered from Parkinson's disease with prominent, relatively drug
      resistant rest tremor. The other four patients had a drug-induced parkinsonian
      tremor due to neuroleptic agents taken for a psychiatric condition. Five of the
      six parkinsonian patients and three of the four psychiatric patients reported
      within a few days a marked and intolerable exacerbation of their tremor. One
      patient in each group was improved, and this improvement was verified in repeated
      examinations. Thus, for unknown reasons, the effect of ethosuximide was not as
      predicted by the monkey model. Among possible explanations is the fact that we
      had chosen patients with drug-resistant tremor.

PMID- 1350061
TI  - Effect of ethosuximide on rest tremor in the MPTP monkey model.
AB  - Based on the hypothesis that low-threshold calcium conductance in the thalamus
      might be involved in the pathophysiology of parkinsonian tremor, ethosuximide was
      given chronically to a monkey previously treated with MPTP and displaying
      exceptionally a typical rest tremor. After 5 days of daily treatment, the tremor
      was reduced by 60%. Diltiazem and verapamil which act on different calcium
      channels had no such effect. Ethosuximide also potentiated the anti-tremor effect
      of the dopamine D2 agonist LY-171555.

PMID- 1350063
TI  - Neuromuscular function and polymorphism of the acetylcholine receptor gamma gene.
AB  - Examination of inbred and wild mice has shown that the gene coding for the
      acetylcholine receptor gamma subunit is polymorphic and the polymorphism
      correlates with differences in neuromuscular function tested by two different
      methods. Polymorphism of the AChR gamma gene was demonstrated after digestion of
      genomic DNA with Pstl and Xbal. These two restriction enzymes demonstrated RFLP
      patterns specific for C57Bl/6J (PSXS) and C3H/HeJ (PRXR) mice, respectively.
      Examination of F1 (C3H/HeJ x C57Bl/6J) and F2 hybrid populations, and other
      murine inbred strains, showed the inheritance and strain specificity of the
      RFLPs. Testing wild mice demonstrated that the PSXS form of the AChR gamma gene
      is the most common in the wild. The AChR gamma and AChR delta subunits are
      closely linked and carried on the same chromosome as several contractile
      proteins. Because these genes are essential for correct neuromuscular development
      and activity, we investigated the possibility that the observed AChR gamma
      polymorphisms mark a haplotype which correlates with variations in neuromuscular
      function. Analysis of exercise times showed a correlation between AChR gamma
      polymorphism and neuromuscular function. To our knowledge, this is the first
      description of AChR polymorphism cosegregating with variations in neuromuscular
      function.

PMID- 1350062
TI  - Postvaccinal parkinsonism.
AB  - A 5-year-old boy, with a history of fever beginning 15 days after a vaccination
      for measles, developed a rigid-akinetic syndrome 3 days after the fever began. A
      spinal tap obtained 1 week after the onset of fever showed pleocytosis with a
      monocellular pattern. A CT scan of the head and EEG did not disclose any
      abnormality. An MRI performed 3 months after the event, however, showed clear-cut
      evidence of bilateral substantia nigra lesions, suggesting secondary gliosis. The
      response to levodopa was good, but adverse reactions appeared early. The child is
      now 7 years old. Bromocriptine, deprenyl, and levodopa have produced a remarkable
      improvement of the parkinsonian features.

PMID- 1350064
TI  - [Influence of succinate on the effectiveness of glutamatergic synaptic
      transmission in surviving slices of rat hippocampus].
AB  - Sodium succinate has been studied for its influence on the efficiency of
      glutamate transmission in the Schaffer collateral synapses and duration of its
      potentiation state caused by high-frequency stimulation in surviving hippocampal
      slices. It is shown that administration of sodium succinate (50 mg/kg i. p.) to
      rats 30 min prior to decapitation stabilizes glutamate transmission in field CA1
      of the rat hippocampal slices and increases duration of its potentiation state.

PMID- 1350065
TI  - Effect of diabetes on in vivo and in vitro hypothalamic somatostatin release.
AB  - In order to better understand the mechanisms underlying the reduction in growth
      hormone (GH) secretion in diabetic rats, we studied hypothalamic somatostatin
      secretion both in vivo (into hypophysial portal blood) and in vitro (from
      hypothalamic fragments) 5, 9 and 30 days after induction of diabetes.
      Experimental diabetes was induced by an intraperitoneal injection of
      streptozotocin (STZ) at a dose of 65 mg/kg. Basal plasma GH was significantly
      reduced in diabetic rats at all stages. Somatostatin levels in hypophysial portal
      blood was unaffected in 5-day STZ-diabetic rats and significantly increased 9
      days after STZ administration. Chronic insulin replacement therapy in diabetic
      animals partly normalized somatostatin levels as well as plasma GH and glucose
      levels. A good correlation was observed between in vivo and in vitro experiments.
      Indeed, somatostatin release from hypothalamic fragments did not change 5 days
      after STZ-induced diabetes and significantly increased 9 and 30 days after STZ
      administration. The in vitro increase in hypothalamic somatostatin secretion was
      observed in 10 as well as in 33 mM glucose concentration in the incubation
      medium. In the same experiment, the in vitro hypothalamic corticotropin-releasing
      factor secretion was lowered 5 and 9 days after diabetes induction. We conclude
      that hypothalamic somatostatin release increases in diabetic rats. These changes
      may contribute to the reduction in GH secretion in these animals. However, since
      these changes occur after the onset of plasma GH decrease, a factor(s) other(s)
      than somatostatin may play a causal role in the reduction in GH secretion.

PMID- 1350066
TI  - Hypothalamic regulation of impaired growth hormone secretion in diabetic rats. 1.
      Studies in streptozotocin-induced diabetic rats.
AB  - Growth hormone (GH) secretion is blunted in diabetic rats. In the present
      experiment we observed that pituitary GH concentrations and the plasma GH
      response to an exogenous dose of growth hormone-releasing hormone (GHRH) is
      decreased in streptozotocin-induced diabetic rats (p less than 0.02) with respect
      to normal rats. In an attempt to determine if increased somatostatin (SRIF)
      secretion is responsible for the decreased GH secretion, we studied the effect of
      modulating SRIF tone on the GH response to GHRH in normal and streptozotocin
      induced diabetic rats. Rats were pretreated with either normal sheep serum and
      saline (NSS+SAL), somatostatin antibodies (SRIF-Ab), or pyridostigmine (PD), an
      acetylcholinesterase inhibitor hypothesized to reduce hypothalamic SRIF
      secretion. Pretreatment of normal rats with SRIF-Ab or PD resulted in an
      increased GH response to exogenous GHRH in comparison to NSS+SAL-pretreated
      normal rats at 5 min postinjection. In contrast, pretreatment of diabetic rats
      with SRIF-Ab or PD did not alter the GH response to exogenous GHRH when compared
      to NSS+SAL-pretreated diabetic animals. These results suggest that the blunted GH
      response to exogenous GHRH observed in streptozotocin-induced diabetic rats may
      not be due to an increase of endogenous SRIF tone.

PMID- 1350067
TI  - Hypothalamic regulation of impaired growth hormone secretion in diabetic rats. 2.
      Studies in spontaneously diabetic BB Worcester rats.
AB  - In the present study we investigated the effects of modulating endogenous
      somatostatin (SRIF) on the GH response to growth hormone-releasing hormone (GHRH)
      in spontaneously diabetic BB/Wor rats and nondiabetic littermates. Plasma growth
      hormone (GH) concentrations following injection of GHRH (500 ng/kg, i.v.) were
      measured in the rats after pretreatment with either normal sheep serum+saline
      (NSS+SAL), somatostatin antibody (SRIF-Ab), or pyridostigmine bromide (PD), an
      acetylcholine esterase inhibitor hypothesized to decrease hypothalamic SRIF tone.
      The GH response to GHRH in spontaneous diabetic rats pretreated with NSS+SAL was
      significantly lower (p less than 0.05) than the response observed in the
      nondiabetic group. SRIF-Ab pretreatment reversed the blunted GH response observed
      in the diabetic rats. However, PD pretreatment was not effective. These results
      indicate that the blunted GH response observed in BB/Wor diabetic rats is
      reversed by neutralization of endogenous SRIF with SRIF-Ab and leads to the
      conclusion that SRIF plays an active role in modulating GH secretion in
      spontaneously diabetic rats. The failure of PD to modulate the GH response
      suggests this acetylcholine agonist is ineffective in this animal paradigm.

PMID- 1350068
TI  - Partial characterization of a neurotransmitter pathway regulating the in vivo
      release of prolactin.
AB  - Nicotinic cholinergic, opiate and serotonergic agonists as well as dopaminergic
      antagonists induce the release of pituitary prolactin. The purposes of the
      present studies were to determine if nicotine, morphine and the serotonin1A (5
      HT1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) utilize a common
      synaptic pathway to release prolactin and, if so, to establish the serial order
      of the receptors involved. We also sought to determine whether the pathway under
      investigation leads to the secretion of prolactin via a mechanism involving
      dopamine, the prolactin inhibitory factor. Male rats with indwelling jugular
      catheters were pretreated with saline, mecamylamine, naltrexone, methysergide or
      bromocriptine. In the saline-treated animals, administration of nicotine,
      morphine, 8-OH-DPAT and haloperidol resulted in significant increases in plasma
      prolactin levels. Mecamylamine pretreatment prevented the prolactin response to
      nicotine only. Naltrexone blocked the stimulation of prolactin release by
      morphine and by nicotine. Methysergide inhibited the effects of 8-OH-DPAT,
      morphine and nicotine but not haloperidol. Bromocriptine blocked the prolactin
      secretion induced by haloperidol as well as by each of the above agonists. Also,
      in dual-immunocytochemically stained sections, tyrosine hydroxylase
      immunoreactive cells and serotonin-immunoreactive processes were detected in
      close anatomical proximity in the dorsomedial arcuate nucleus. These data
      indicate that nicotine, morphine and 8-OH-DPAT act to release prolactin via a
      common synaptic pathway expressing nicotinic cholinergic, opiate, and 5-HT1A
      receptors at synapses arranged serially in that functional order. Furthermore,
      the data indicate that the in vivo secretion of prolactin via this pathway may
      ultimately occur through the inhibition of dopamine release.

PMID- 1350069
TI  - Neurotransmitter-induced hypothalamic-pituitary-adrenal axis responsiveness is
      defective in inflammatory disease-susceptible Lewis rats: in vivo and in vitro
      studies suggesting globally defective hypothalamic secretion of corticotropin
      releasing hormone.
AB  - The susceptibility of female Lewis (LEW/N) rats to the development of
      streptococcal cell wall (SCW)-induced arthritis and other autoimmune phenomena is
      associated with the inability of their hypothalamic-pituitary-adrenal (HPA) axis
      to adequately respond to inflammatory stimuli. In contrast, resistance to the
      development of SCW-induced arthritis and other inflammatory autoimmune
      manifestations in histocompatible female Fischer rats (F344/N) is related to
      their intact HPA axis response to inflammatory mediators. To evaluate the
      mechanism and the specificity of the HPA axis defect in LEW/N rats, we examined
      the ability of three major excitatory neurotransmitter systems to activate the
      HPA axis in both Lewis and Fisher rats. The responsiveness of plasma ACTH and
      corticosterone to the cholinergic muscarinic receptor agonist arecoline, the
      alpha 1-adrenergic receptor agonist methoxamine and the serotonin (5-HT) type 2
      receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane were significantly
      blunted and/or abolished in LEW/N compared to F344/N rats. To localize the HPA
      axis defect to the hypothalamic CRH neuron, we evaluated the ability of explanted
      hypothalami from the two strains to secrete immunoreactive CRH in vitro, in
      response to acetylcholine (ACh), norepinephrine (NE), 5-HT and the 5-HT agonist
      quipazine. LEW/N hypothalami released less immunoreactive CRH (iCRH) in response
      to ACh, NE, 5-HT and quipazine than F344/N hypothalami. The dose-response curves
      of these compounds in the former were shifted to the right and/or abolished,
      suggesting decreased sensitivity of LEW/N hypothalami to these
      neurotransmitters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350070
TI  - Opposite effects of neurotensin on dopamine inhibition in different regions of
      the rat brain: an iontophoretic study.
AB  - Anatomical, biochemical and behavioral data suggest functional interactions
      between dopamine and neurotensin in regions of the brain receiving a co-existent
      and/or distinct innervation by these two transmitters. We therefore measured and
      compared the effects of iontophoretically applied dopamine and neurotensin in the
      prefrontal and anterior cingulate cortex (co-existent innervation) vs the nucleus
      accumbens and neostriatum (distinct innervation) of urethane-anesthetized rats.
      In every region, the firing rate of most spontaneously active neurons was
      depressed by dopamine. Neurotensin had no effect on the same cells, except for a
      few nucleus accumbens units which were inhibited by the peptide. When dopamine
      and neurotensin were concomitantly applied, the magnitude of maximal inhibitions
      induced by dopamine was modified in the majority of neurons tested. A significant
      decrease in dopamine inhibition was observed in 100% of anterior cingulate, 74%
      of prefrontal cortex and 48% of accumbens units. On the contrary, in neostriatum,
      dopamine inhibition was significantly increased in 60% of the units tested. In
      every region, the remaining neurons showed less than 30% changes in dopamine
      responsiveness, and were therefore considered unaffected by neurotensin. In the
      anterior cingulate cortex, inhibitions, respectively, induced by the dopamine D1
      agonist, SKF 38393, and the D2 agonist, LY 171555, were also decreased by
      simultaneous application of neurotensin. Together with currently available data
      on the cellular localization of neurotensin receptors in rat brain, these results
      suggest that the modulation of dopamine inhibition by neurotensin may have
      opposite effects depending on whether the neurotensin receptors are located
      postsynaptically on target neurons (antagonistic effects) or presynaptically on
      dopamine terminals (potentiating effects).

PMID- 1350071
TI  - Chemoreceptor A-fibres in the human carotid body contain tyrosine hydroxylase and
      neurofilament immunoreactivity.
AB  - Previous retrograde tracing studies on rat and guinea-pig showed a projection of
      sensory tyrosine hydroxylase-immunoreactive neurons to the region of the carotid
      bifurcation via the carotid sinus nerve. In the present study, focussing on the
      sensory innervation of the human carotid body, antisera to tyrosine hydroxylase
      and other catecholamine synthesizing enzymes were applied for an
      immunohistochemical investigation of carotid bodies obtained at autopsy. In
      addition, an array of antisera directed to non-enzyme antigens known to be
      present in viscero-afferent neurons were incorporated in the study. The glomic
      lobules consisting of glomus cells and sustentacular cells contained a variable
      number of enzyme-immunoreactive glomus cells. Arteries were supplied by nerve
      fibres displaying the full phenotype of sympathetic noradrenergic axons, i.e.
      immunoreactivity to tyrosine hydroxylase, aromatic-L-amino-acid-decarboxylase and
      dopamine-beta-hydroxylase. The glomic lobules, however, were densely innervated
      by tyrosine hydroxylase-immunoreactive axons lacking immunoreactivity to aromatic
      L-amino-acid-decarboxylase and dopamine-beta-hydroxylase. These fibres reacted
      with neurofilament 160kD-antibody but were devoid of immunoreactivity to all
      neuropeptides tested (calcitonin gene-related peptide, somatostatin, substance
      P). Ultrastructurally, tyrosine hydroxylase/neurofilament 160kD-immunoreactive
      axons gave rise to large axonal swellings filled with mitochondria and vesicles,
      and established extensive contacts to glomus cells. Nerve bundles surrounded by a
      perineural sheath contained both myelinated (2.0-2.8 microns in diameter) and
      unmyelinated (0.14-3.0 microns) tyrosine hydroxylase-immunoreactive axons. Most
      of the unmyelinated immunoreactive axons were running singularly within a Schwann
      cell-sheath. Judged from the pattern of immunoreactivities as well as their
      preterminal and terminal ultrastructure, tyrosine hydroxylase-immunoreactive
      axons innervating glomus cells are of sensory origin. Although final proof by
      retrograde tracing cannot be presented in man, this conclusion is supported by
      experimental evidence in laboratory animals. The myelinated immunoreactive axons
      correspond to chemoreceptor A-fibres whereas the classification of the large
      unmyelinated immunoreactive axons has yet to be established. The lack of
      immunoreactivity to the dopamine-synthesizing enzyme, aromatic-L-amino-acid
      decarboxylase, in this fibre type does not support the view of dopamine being the
      primary transmitter of chemoreceptor afferents.

PMID- 1350072
TI  - When does Parkinson's disease begin?
AB  - A long preclinical or asymptomatic period may occur in Parkinson's disease (PD).
      Many long-latency parkinsonian syndromes exist. The presence of early-life risk
      factors is consistent with a long prodromal period. Marked degeneration of the
      substantia nigra and loss of striatal dopamine are necessary before clinical
      symptoms develop. Lewy bodies, the histological hallmark of PD, occur in 10% of
      normal individuals over age 50. Clinical symptoms develop slowly and are often
      intermittent in early PD. Nonmotor signs, eg, depression or sensory changes,
      often precede motor signs by many years. Reduction of striatal dopamine can be
      detected with PET in "at-risk" asymptomatic individuals. Individual sensitivity
      to drug-induced parkinsonism also suggests a preclinical state. Biologic markers
      may eventually be able to detect preclinical PD.

PMID- 1350073
TI  - Dopamine agonists used as monotherapy in de novo PD patients: comparisons with
      selegiline.
AB  - Studies indicate that selegiline, a monoamine oxidase type B inhibitor, slows
      progression of Parkinson's disease (PD) and delays the need for levodopa. While
      dopamine agonists also delay the need for levodopa because of their symptomatic,
      antiparkinsonian effect, only recently has it been proposed that agonists may
      also have a protective effect. When dopamine agonists are used as monotherapy in
      newly diagnosed PD patients, fewer patients improve than on levodopa, but fewer
      patients develop response fluctuations. This might indicate that dopamine
      agonists have a protective, as well as a symptomatic, effect, as the lack of
      response fluctuations may indicate that dopamine agonists protect nigral neurons.
      Response fluctuations may result from destruction of nigral neurons.

PMID- 1350074
TI  - The role of the regulatory enzymes of catecholamine synthesis in Parkinson's
      disease.
AB  - The major neuropathology of Parkinson's disease (PD) is the degeneration of
      nigrostriatal dopamine (DA), resulting in a deficiency of DA, and of the enzyme
      tyrosine hydroxylase (TH), which catalyzes the synthesis of L-dopa. The
      symptomatic treatment of PD consists of replenishing DA by administering L-dopa,
      which is enzymatically converted to DA in the striatum. The increase of TH
      activity by modification of the enzyme leads to an increased synthesis of
      striatal L-dopa, and thereby replenishes the missing DA more efficiently. The
      activity of TH is increased by protein kinase-dependent phosphorylation of the
      enzyme or by inhibition of dephosphorylation with specific phosphatase
      inhibitors. Thus, modification of TH results in an activated form of the enzyme,
      which might provide a basis for developing new strategies in the treatment of PD.
      The extraneuronal enzyme, catechol-O-methyl transferase (COMT), inactivates
      catecholamines by O-methylation, and its inhibition leads to increased levels of
      striatal DA. The availability of selective and nontoxic COMT inhibitors makes it
      possible to assess their therapeutic role in treatment of PD. The intraneuronal
      enzymes, monoamine oxidase (MAO)-A and MAO-B, inactivate catecholamines and other
      biogenic amines, such as serotonin, by deamination. Inhibition of these enzyme
      activities leads to increased levels of striatal DA. The irreversible MAO-B
      inhibitor selegiline was shown to exert antiparkinsonian activity, especially in
      the early stages of parkinsonism. Selegiline also prevents the 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in MPTP-treated mice and
      monkeys. Its role in the prevention of the disease is under investigation in
      several clinical centers.

PMID- 1350075
TI  - Kainic acid depresses the ex vivo release of dynorphin B and glutamate from rat
      hippocampal mossy fiber synaptosomes.
AB  - This experiment examined the effects of intracerebroventricularly (i.c.v.)
      administered kainic acid (KA) on the subsequent ex vivo release of L-glutamate
      (Glu) and dynorphin B-like immunoreactivity (Dyn B-LI) from isolated rat
      hippocampal mossy fiber (MF) synaptosomes at 4.5 h, 20 h or 48 h after
      administration of 0.5 microgram/microliter KA. The Dyn B-LI content in the
      synaptosomal fraction initially decreased at 4.5 h and then rebounded and
      remained elevated above control levels at 20 h and 48 h. The K(+)-evoked release
      of Dyn B-LI from the synaptosomes was markedly depressed at 4.5 h after KA and
      remained significantly below control levels at 20 h and 48 h. In contrast, KA
      caused no change in the K(+)-evoked release of Glu at 4.5 h as compared to
      control levels, but did result in a significant decrease in Glu release at 20 h
      and 48 h. These data indicate a persistent effect of i.c.v. KA on
      neurotransmission at MF-CA3 synapses in rat hippocampus, resulting in a
      suppression of the release of Glu as well as the opioid peptide, Dyn B.

PMID- 1350076
TI  - Age-related changes in transmitter glutamate and NMDA receptor/channels in the
      brain of senescence-accelerated mouse.
AB  - The senescence-accelerated mouse (SAM-P/8) is known as a murine model of aging
      and memory dysfunction. In the hippocampus and cerebral cortex of P/8, the
      contents of glutamic acid and glutamine were significantly higher than those of
      normal strain R/1 during 2 and 14 months. High K(+)-evoked endogenous glutamic
      acid release from the slices of P/8 was increased in comparison with R/1 at 9 and
      11 months. In addition, the Bmax of [3H]dizocilpine (MK-801, channel blocker for
      N-methyl-D-aspartic acid receptor/channel) binding in the cerebral cortex was age
      dependently decreased in P/8 but not in R/1. These results suggest that synaptic
      dysfunctions in the glutamatergic system occur in the CNS of SAM-P/8.

PMID- 1350077
TI  - Inhibition of cisplatin-induced emesis in ferrets by the non-NMDA receptor
      antagonists NBQX and CNQX.
AB  - The excitatory amino acid (EAA) receptor antagonists, 2,3-dihydroxy-6-nitro-7
      sulphamoylbenzo(f)quinoxaline (NBQX) and 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX), which preferentially block non-N-methyl-D-aspartate (non-NMDA) subtypes
      of EAA receptors, effectively inhibit cisplatin-induced emesis in ferrets. A high
      dose of cisplatin (10 mg/kg i.v.) was used which induced emesis in all saline
      treated control ferrets. At 10 mg/kg i.v., NBQX totally prevented cisplatin
      induced emesis in 5 of 6 ferrets and CNQX totally prevented emesis in 3 of 5
      ferrets. By comparison, each of the 5-HT3 inhibitors, zacopride and ondansetron,
      at 1.0 mg/kg i.v. (a dose considered in the high therapeutic range for
      controlling emesis by these compounds), totally prevented emesis in 2 of 5
      ferrets. It is concluded that non-NMDA antagonists effectively inhibit cisplatin
      induced emesis. They are potential antiemetic compounds, alone or in combination
      with 5-HT3 antagonists or other more conventional drugs of choice.

PMID- 1350078
TI  - Low concentrations of N-methyl-D-aspartate inhibit the induction of long-term
      potentiation in rat hippocampal slices.
AB  - We have examined the effects of excitatory amino acids on tetanus-induced long
      term potentiation (LTP) in the CA1 region of rat hippocampal slices. Agonists
      acting at N-methyl-D-aspartate (NMDA) receptors, including NMDA, aspartate and
      glutamate, completely block the development of LTP when administered for 5 min
      prior to tetanic stimulation. Additionally, and unlike the NMDA receptor
      antagonist 2-amino-5-phosphonovalerate (APV), NMDA blocks LTP when administered
      for 5 min immediately following the electrical tetanus. The effective
      concentrations of NMDA are subthreshold for depolarizing CA1 neurons. These
      results indicate that under certain conditions NMDA receptor activation prevents
      CA1 LTP.

PMID- 1350079
TI  - Depletion of dopamine binding sites and changes in dopamine and
      dihydroxyphenylacetic acid levels in 17- and 90-day-old rat striatum after
      irreversible receptor antagonism.
AB  - Irreversible antagonism of dopamine (DA) receptors by the alkylating compound N
      ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) results in a depression of DA
      agonist mediated behaviors in adult, but not preweanling rats. DA D1 and D2
      receptors, dihydroxyphenylacetic acid (DOPAC) and DA levels were assessed in 17-
      and 90-day-old rats in order to identify a neurochemical mechanism for this
      difference. EEDQ caused a depletion in D1 and D2 receptors in both young and
      adult rats, with the depletion in adults being relatively greater. In both age
      groups, EEDQ caused an unexpected decrease in DA levels which returned to normal
      levels by 30 days post-injection. In addition, DOPAC levels of adult rats, but
      not rat pups, were elevated after EEDQ treatment. The depletion of endogenous DA
      levels must be considered when interpreting the effects of EEDQ. Age-dependent
      differences in DA metabolism may be important for understanding the ontogenetic
      differences in EEDQ's behavioral effects.

PMID- 1350080
TI  - Nurse practitioners and physician assistants: are they the same?

PMID- 1350081
TI  - Perspectives on nursing knowledge.
AB  - On May 19, 1991, in Tokyo, Japan, four nurse theorists participated in a panel
      discussion at Discovery International, Inc.'s Biennial Nurse Theorist Conference.
      The participants were Imogene M. King, Hildegard E. Peplau, Rosemarie Rizzo
      Parse, and Martha E. Rogers. The goal of the conference was to present the latest
      views on nursing knowledge of these nurse leaders. The panel discussion provided
      the nurse theorists with an opportunity to engage in dialogue regarding issues of
      concern to the audience. The panel moderator was Hiroko Minami of St. Luke's
      College of Nursing in Tokyo.

PMID- 1350082
TI  - Basic concepts of molecular biology as applied to pediatric and adolescent
      gynecology.
AB  - Recombinant DNA techniques have increased our understanding of genetic disorders
      and facilitated their diagnosis and may eventually lead to therapy. Expression
      may be assessed and quantified by Northern blot analysis, whereas in situ
      hybridization may localize the transcript. Southern blotting has been the
      standard method to identify gene mutations and RFLPs, which are useful in the
      diagnosis of many different disorders. Special multiallelic RFLPs produce a DNA
      fingerprint particularly useful in paternity testing and forensic medicine. PCR
      has greatly reduced the time and expense to diagnose genetic disorders, and has
      an enormous number of applications both clinically and at the research level.
      These techniques along with DNA sequencing are currently being used in the human
      genome project, which may some day allow "DNA typing" of individuals for any gene
      of interest. There is no doubt that new techniques in molecular biology will
      continue to evolve so that the goal of gene therapy for many disorders may be
      possible in the future.

PMID- 1350083
TI  - A new transthyretin mutation associated with amyloidotic vitreous opacities.
      Asparagine for isoleucine at position 84.
AB  - An inherited type of amyloidosis was suspected in an individual of Italian
      descent who presented with vitreous opacities. Although no family history of
      amyloidosis was apparent, the patient's transthyretin gene was examined and found
      not to possess any of the known transthyretin mutations. Complete DNA sequencing
      revealed a substitution of adenine for thymine in the second base of codon 84
      causing an amino acid change of asparagine for isoleucine. The mutation was
      confirmed by demonstrating the loss of an Sfa N1 restriction endonuclease site.
      Allele-specific DNA amplification by polymerase chain reaction also was used to
      confirm the mutation. Either of these tests can be used for diagnosis. Asparagine
      84 represents the second mutation associated with amyloidosis to occur at codon
      84.

PMID- 1350084
TI  - Ethanol ingestion combined with lowered carbohydrate intake enhances the
      initiation of diethylnitrosamine liver carcinogenesis in rats.
AB  - The effect of ethanol on the initiation of diethylnitrosamine- (DEN) induced
      liver carcinogenesis was investigated in rats. In the first experiment, eight
      week-old male Wistar rats were maintained on four liquid diets: a basal diet
      (Group 1), a low-carbohydrate (low-CHO) diet (Group 2), a basal diet+ethanol
      (Group 3), or a low-CHO diet+ethanol (Group 4). After three weeks on these diets,
      50 mg/kg of DEN was injected intraperitoneally. The plasma glutamic-oxaloacetic
      transaminase activity in Group 4 was higher 24 hours after DEN administration
      than in Groups 1 and 3. The plasma glutamic-pyruvic transaminase activity in
      Groups 3 and 4 was higher than in Groups 1 and 2. The number of gamma
      glutamyltranspeptidase-positive foci per unit liver area 41 weeks after DEN
      administration was higher in Group 4 than in Group 1. The area of gamma
      glutamyltranspeptidase-positive foci was greater in Groups 2 and 4 than in Group
      1. In the second experiment, Groups 1 and 4 were given DEN orally (25 or 75
      mg/kg). Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic
      transaminase activities 24 hours after DEN administration were significantly
      higher in Group 4 than in Group 1, but only when the dose of DEN was 75 mg/kg. In
      contrast, the number and area of placental glutathione S-transferase-positive
      foci per unit liver area were greater in Group 4 than in Group 1 only after 25
      mg/kg of DEN. Thus the severity of hepatotoxicity and the incidence of
      precancerous liver lesions were not necessarily correlated. These findings
      together indicate that a combination of ethanol and a low-CHO diet enhances DEN
      induced liver carcinogenesis in rats by increasing the bioactivation of DEN in
      the liver.

PMID- 1350085
TI  - [Treatment of asthma in children].

PMID- 1350086
TI  - [Multiple cholesterol embolism mimicking periarteritis nodosa].
AB  - Ten men aged 56 to 84 were hospitalized with a diagnosis of periarteritis nodosa,
      whereas they had multiple cholesterol embolism. The diagnosis was corrected post
      mortem in the first 3 patients and subsequently in live patients. The
      particularly misleading clinical manifestations were neurological (polyneuritis
      in 5 cases, mononeuritis in 1, central nervous system disorders in 3), pulmonary
      (alveolar haemorrhage in 2 cases, respiratory failure of unknown mechanism in 4)
      and pericardial (2 cases). Five patients had eosinophilia (more than 500
      eosinophils/mm3). The elements that led to the correct diagnosis were the
      presence of vascular risk factors in all 10 patients (but hyperlipidaemia in only
      one), severe complications of the atheromatous disease in all cases, a
      precipitating or aggravating factor in 8 patients (anticoagulant therapy in 7,
      arteriography in 6) and the finding of purple or necrotic toes (6 cases).
      Histological (5 cases) and/or ophthalmological (2 cases) evidence was obtained in
      only 6 patients. Seven patients died 1 to 3 years after the onset of the
      disorders. Studies on low-density lipoprotein metabolism are in progress to
      determine the mechanism of clinical manifestations unexplainable by embolism.

PMID- 1350087
TI  - Leucine-responsive regulatory protein controls the expression of both the pap and
      fan pili operons in Escherichia coli.
AB  - The methylation blocking factor gene (mbf) in Escherichia coli is required for
      specific methylation inhibition of two DNA GATC sites upstream of the papBA pilin
      promoter and transcriptional activation of pap. Complementation and mutational
      analysis using pap-lac and ilvIH-lac operon fusions indicates that the mbf gene
      is identical to a recently described global regulatory gene lrp (leucine
      responsive regulatory protein) that acts as a positive regulator of some genes
      and a negative regulator of others in E. coli. DNA sequence analysis of an
      mbf::mTn10 insertion showed that the mbfDNA sequence was identical to lrp. Thus
      Lrp inhibits DNA methylation at specific GATC sites. We also show that Lrp
      positively regulates transcription of the fan operon, which encodes K99 pili of
      diarrheagenic E. coli. Purified Lrp was found to bind to DNA fragments
      encompassing the pap and fan promoters, which is consistent with previous results
      indicating that Lrp controls gene expression by binding to regulatory DNA sites.
      Exogenous leucine significantly reduced fan transcription and K99 pili
      expression, similar to results obtained with the ilvIH operon. However, pap gene
      expression was unresponsive to leucine, which distinguishes pap from other lrp
      regulated genes whose expression is modulated by leucine.

PMID- 1350088
TI  - Humanization of an anti-p185HER2 antibody for human cancer therapy.
AB  - The murine monoclonal antibody mumAb4D5, directed against human epidermal growth
      factor receptor 2 (p185HER2), specifically inhibits proliferation of human tumor
      cells overexpressing p185HER2. However, the efficacy of mumAb4D5 in human cancer
      therapy is likely to be limited by a human anti-mouse antibody response and lack
      of effector functions. A "humanized" antibody, humAb4D5-1, containing only the
      antigen binding loops from mumAb4D5 and human variable region framework residues
      plus IgG1 constant domains was constructed. Light- and heavy-chain variable
      regions were simultaneously humanized in one step by "gene conversion
      mutagenesis" using 311-mer and 361-mer preassembled oligonucleotides,
      respectively. The humAb4D5-1 variant does not block the proliferation of human
      breast carcinoma SK-BR-3 cells, which overexpress p185HER2, despite tight antigen
      binding (Kd = 25 nM). One of seven additional humanized variants designed by
      molecular modeling (humAb4D5-8) binds the p185HER2 antigen 250-fold and 3-fold
      more tightly than humAb4D5-1 and mumAb4D5, respectively. In addition, humAb4D5-8
      has potency comparable to the murine antibody in blocking SK-BR-3 cell
      proliferation. Furthermore, humAb4D5-8 is much more efficient in supporting
      antibody-dependent cellular cytotoxicity against SK-BR-3 cells than mumAb4D5, but
      it does not efficiently kill WI-38 cells, which express p185HER2 at lower levels.

PMID- 1350089
TI  - Development of antibodies against the rat brain somatostatin receptor.
AB  - Somatostatin (SRIF) is a neurotransmitter in the brain involved in the regulation
      of motor activity and cognition. It induces its physiological actions by
      interacting with receptors. We have developed antibodies against the receptor to
      investigate its structural properties. Rabbit polyclonal antibodies were
      generated against the rat brain SRIF receptor. These antibodies (F4) were able to
      immunoprecipitate solubilized SRIF receptors from rat brain and the cell line AtT
      20. The specificity of the interaction of these antibodies with SRIF receptors
      was further demonstrated by immunoblotting. F4 detected SRIF receptors of 60 kDa
      from rat brain and adrenal cortex and the cell lines AtT-20, GH3, and NG-108,
      which express high densities of SRIF receptors. They did not detect
      immunoreactive material from rat liver or COS-1, HEPG, or CRL cells, which do not
      express functional SRIF receptors. In rat brain, 60-kDa immunoreactivity was
      detected by F4 in the hippocampus, cerebral cortex, and striatum, which have high
      densities of SRIF receptors. However, F4 did not interact with proteins from
      cerebellum and brain stem, which express few SRIF receptors. Immunoreactive
      material cannot be detected in rat pancreas or pituitary, which have been
      reported to express a 90-kDa SRIF receptor subtype. The selective detection of 60
      kDa SRIF receptors by F4 indicates that the 60- and 90-kDa SRIF receptor subtypes
      are immunologically distinct. The availability of antibodies that selectively
      detect native and denatured brain SRIF receptors provides us with a feasible
      approach to clone the brain SRIF receptor gene(s).

PMID- 1350090
TI  - Homosynaptic long-term depression in area CA1 of hippocampus and effects of N
      methyl-D-aspartate receptor blockade.
AB  - We tested a theoretical prediction that patterns of excitatory input activity
      that consistently fail to activate target neurons sufficiently to induce synaptic
      potentiation will instead cause a specific synaptic depression. To realize this
      situation experimentally, the Schaffer collateral projection to area CA1 in rat
      hippocampal slices was stimulated electrically at frequencies ranging from 0.5 to
      50 Hz. Nine hundred pulses at 1-3 Hz consistently yielded a depression of the CA1
      population excitatory postsynaptic potential that persisted without signs of
      recovery for greater than 1 hr after cessation of the conditioning stimulation.
      This long-term depression was specific to the conditioned input, ruling out
      generalized changes in postsynaptic responsiveness or excitability. Three lines
      of evidence suggest that this effect is accounted for by a modification of
      synaptic effectiveness rather than damage to or fatigue of the stimulated inputs.
      First, the effect was dependent on the stimulation frequency; 900 pulses at 10 Hz
      caused no lasting change, and at 50 Hz a synaptic potentiation was usually
      observed. Second, the depressed synapses continued to support long-term
      potentiation in response to a high-frequency tetanus. Third, the effects of
      conditioning stimulation could be prevented by application of NMDA receptor
      antagonists. Thus, our data suggest that synaptic depression can be triggered by
      prolonged NMDA receptor activation that is below the threshold for inducing
      synaptic potentiation. We propose that this mechanism is important for the
      modifications of hippocampal response properties that underlie some forms of
      learning and memory.

PMID- 1350091
TI  - Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP
      phosphodiesterase beta subunit.
AB  - The beta subunit of the cGMP phosphodiesterase (PDE) gene has been identified as
      the candidate gene for retinal degeneration in the rd mouse. To study the
      molecular mechanisms underlying degeneration and the potential for gene repair,
      we have expressed a functional bovine cGMP PDE beta subunit in transgenic rd
      mice. One transgenic mouse line showed complete photoreceptor rescue across the
      entire span of the retina. A second independently derived line showed partial
      rescue in which photoreceptors in the superior but not the inferior hemisphere of
      the retina were rescued. In the latter animals, intermediate stages of
      degeneration were observed in the transition zone between rescued and diseased
      photoreceptors. Pathologic changes in the retina ranged from vesiculation of the
      basalmost outer segment discs in otherwise structurally intact rod cells to
      photoreceptors with highly disorganized outer segments and intact inner segments.
      Totally or partially rescued retinas showed a corresponding restoration of cGMP
      PDE activity, whereas nonrescued retinas had minimal enzyme activity,
      characteristic of the rd phenotype. These transgenic animals provide models for
      studying the molecular basis of retinal degenerative disease and conclusively
      demonstrate that the phenotype of rd mice is produced by a defect in the beta
      subunit of cGMP PDE.

PMID- 1350092
TI  - Organization and evolution of the human epidermal keratinocyte transglutaminase I
      gene.
AB  - Transglutaminases (TGases; protein-glutamine:amine gamma-glutamyltransferase, EC
      2.3.2.13) are calcium-dependent crosslinking enzymes that modify proteins
      posttranslationally. Several distinct types of TGases have been identified, which
      appear to be encoded by a family of closely related genes. We isolated the gene
      encoding human keratinocyte-specific type I TGase (TGase I) and characterized its
      chromosomal organization. The TGase I gene consists of 15 exons separated by 14
      introns and exhibits a restriction fragment length polymorphism. Exons appear to
      encode functional and/or structural domains: exon I and part of exon XV encode
      untranslated regions, whereas exons VII and XI contain the active site and a
      presumptive calcium-binding domain, respectively. Interestingly, exon VI of TGase
      I contains a consensus Arg-Gly-Asp tripeptide sequence whose presence suggests an
      intriguing extracellular function for the enzyme. We present a likely
      phylogenetic tree for seven known members of the TGase family based on amino acid
      sequence similarity. Arguments presented suggest that the active enzyme evolved
      first and the structural human erythrocyte membrane protein 4.2 (band 4.2) has
      undergone a rapid change in amino acid sequence. It follows that band 4.2 evolved
      from the type II TGases, whereas factor XIII subunit a evolved from the type I
      group.

PMID- 1350093
TI  - Cloning of the yeast FAS3 gene and primary structure of yeast acetyl-CoA
      carboxylase.
AB  - We have isolated and determined the nucleotide sequence of the yeast FAS3 gene,
      which encodes acetyl-CoA carboxylase (EC 6.4.1.2). The sequence has an open
      reading frame of 6711 bases coding for a protein of 2237 amino acids with a
      calculated molecular weight of 250,593. The presence of the unique biotin-binding
      site, Met-Lys-Met, and the known CNBr peptide and COOH-terminal sequences
      confirmed the nucleotide-derived amino acid sequence. The yeast, chicken, and rat
      carboxylases have an overall sequence identity of 34%, suggesting that the
      eukaryotic carboxylase evolved from a single ancestral gene. The amino acid
      sequences of yeast fatty acid synthase subunits are least homologous with the
      animal synthase sequences, whereas carboxylase sequences are highly conserved.
      The sequences of the ATP, HCO3-, and CoA binding sites of the carboxylases are
      also well conserved (approximately 50% identical). The sequences surrounding the
      biotin binding site are poorly conserved, suggesting that this sequence may not
      be critical as long as the biotin is available for carboxylase reactions. On the
      basis of this sequence identity, we have defined the putative biotin carboxylase
      and transcarboxylase domains.

PMID- 1350094
TI  - Amino acid substitutions in the sixth transmembrane domain of P-glycoprotein
      alter multidrug resistance.
AB  - Eukaryotic cells can display resistance to a wide range of natural-product
      chemotheraputic agents by the expression of P-glycoprotein (pgp), a putative
      plasma membrane transporter that is thought to mediate the efflux of these agents
      from cells. We have identified, in cells selected for multidrug resistance with
      actinomycin D, a mutant form of pgp that contains two amino acid substitutions
      within the putative sixth transmembrane domain. In transfection experiments, this
      altered pgp confers a cross-resistance phenotype that is altered significantly
      from that conferred by the normal protein, displaying maximal resistance to
      actinomycin D. These results strongly implicate the sixth transmembrane domain in
      the mechanism of pgp drug recognition and efflux. Moreover, they indicate a close
      functional homology between pgp and the cystic fibrosis transmembrane regulator
      in which the sixth transmembrane domain has also been shown to influence
      substrate specificity.

PMID- 1350097
TI  - Exocytosis by synaptic terminals innervating the adrenal gland of the goldfish
      reveals multiple domains within the plasmalemma.
AB  - The adrenal chromaffin gland of the goldfish has typical synaptic terminals
      embedded in its surface which are homologues of the cholinergic fibres
      innervating the mammalian adrenal medulla. The terminals contain both lucent
      synaptic vesicles and larger secretory granules with dense cores, known to be
      storage sites for transmitters and peptides, respectively. Three domains are
      present within the terminal plasmalemma. Exocytosis of vesicles is thought to be
      associated with a 'synaptic domain' marked by synaptic thickenings around which
      the vesicles cluster. Exocytosis of granules, stimulated by high K+ and
      visualized with the aid of tannic acid, is almost exclusively associated with
      areas of the membrane adjacent to chromaffin cells, and in particular with
      unspecialized regions which constitute the 'parasynaptic domain', creating a
      pattern of targeted secretory discharge. Sites of release within the 'non
      synaptic domain', which is sheathed in glial cell lamellae, are extremely rare,
      despite the expansive character of this domain and the close association of
      granules with the plasmalemma within it. The pattern of secretory release
      described may be correlated with the position of the terminals at the surface of
      the innervated organ.

PMID- 1350096
TI  - Molecular identification of Wolbachia, the agent of cytoplasmic incompatibility
      in Drosophila simulans, and variability in relation with host mitochondrial
      types.
AB  - Sequences of a segment of the 16S ribosomal DNA of Wolbachia, a rickettsia-like
      microorganism responsible for cytoplasmic incompatibility in Drosophila simulans,
      have been obtained after polymerase chain reaction (PCR) amplification. Their
      comparison with other eubacterial sequences allows us to assign these
      endosymbionts to the alpha subdivision of purple bacteria. Four related sequences
      have been obtained for microorganisms carried by eight isofemale lines
      representative of the three mitochondrial types of D. simulans. Their phylogeny
      and level of divergence do not parallel that of the mitochondrial DNA, suggesting
      that several independent infections occurred. There is no direct relation between
      bacterial phylogeny and formerly identified incompatibility types.

PMID- 1350095
TI  - Actions of dopamine and dopaminergic drugs on cloned serotonin receptors
      expressed in Xenopus oocytes.
AB  - Using electrophysiological techniques, we studied interactions of dopamine and
      selected dopaminergic drugs with serotonin (5-hydroxytryptamine; 5-HT) receptors
      expressed in Xenopus oocytes by RNAs transcribed from cloned cDNAs. Oocytes
      showing strong expression of 5-HT1c and 5-HT2 receptors became weakly responsive
      to the neurotransmitter dopamine, which, like 5-HT, elicited Cl- currents through
      activation of the phosphatidylinositol/Ca2+ messenger pathway. The two types of 5
      HT receptors showed similar sensitivity to dopamine; threshold responses were
      activated at concentrations as low as 1 microM. However, maximum dopamine
      responses were only 5-20% of maximum responses activated by 5-HT. The dopamine D1
      receptor antagonist SCH 23390 was a potent agonist on 5-HT1c and 5-HT2 receptors.
      SCH 23390 elicited currents at concentrations as low as 1 nM, but maximum
      responses were again only 5-20% of those activated by 5-HT. Fenoldopam, a
      dopamine D1 receptor agonist, also interacted with 5-HT1c and 5-HT2 receptors,
      eliciting threshold responses between 10 and 20 nM. Our experiments raise the
      possibility that low micromolar concentrations of dopamine can cause weak
      activation and concomitant desensitization of serotoninergic systems in vivo and
      demonstrate that benzazepines can interact with 5-HT receptors at nanomolar
      concentrations.

PMID- 1350098
TI  - Activation of ATP-dependent K+ currents in intact skeletal muscle fibres by
      reduced intracellular pH.
AB  - We have used three-microelectrode voltage clamp in conjunction with the ammonium
      prepulse method to investigate the effects of lowered intracellular pH (pHi) on
      resting potassium currents of frog skeletal muscle fibres. Potassium currents
      were recorded in 40 mM K+, Cl(-)-free solution in response either to voltage
      steps or ramps. An ammonium prepulse (2 h) reduced pHi to 6.45 from a control
      value of 7.19. The intracellular ATP concentration, measured with high-pressure
      liquid chromatography (HPLC), was unchanged by this procedure. Mean outward
      potassium currents were larger in low pHi than in control fibres, being about
      twice as large at +40 mV, whereas mean inward currents were very similar in
      control and low-pHi fibres. The sulphonylurea glibenclamide blocked single KATP
      channels in excised patches with a Kd of 3 microM. In intact fibres 50 microM
      glibenclamide had no effect on K+ currents in controls but reduced currents in
      low-pHi fibres. In the presence of glibenclamide, K+ currents in low-pHi fibres
      were not significantly different from those in control fibres. We suggest that
      reduced pHi in intact skeletal muscle fibres opens ATP-dependent potassium
      channels (KATP channels), as has been shown to occur in excised patches of
      membrane.

PMID- 1350099
TI  - Early changes in the development of dopaminergic neurotransmission after maternal
      exposure to cannabinoids.
AB  - Perinatal exposure to cannabinoid derivatives has been shown to affect brain
      development. In this work, we studied the changes induced by maternal exposure to
      cannabinoids during gestation and lactation on the dopaminergic activity in the
      prosencephalic area of offspring of several days of development. This brain area
      contains an increasing population of dopaminergic terminals from the different
      dopaminergic pathways that become differentiated in the adult rat. We measured
      the endogenous content of dopamine and its intraneuronal metabolite, L-3,4
      dihydroxyphenylacetic acid, and the activity of tyrosine hydroxylase as indices
      of dopaminergic activity. Results showed that perinatal exposure to cannabinoids
      caused several changes in the evolution of the dopaminergic indices studied.
      These changes were mainly observed in males. The only alteration in females
      occurred on the tenth day of development: An increase in dopamine content was
      observed with no changes in either the content of L-3,4-dihydroxyphenylacetic
      acid or tyrosine hydroxylase activity. In males, the content of both dopamine and
      L-3,4-dihydroxyphenylacetic acid were decreased on the day previous to birth in
      the animals exposed to cannabinoids. Although the reduction in its metabolite
      disappeared on the fifth day, the decrease in dopamine was maintained and it was
      correlated with a decrease in tyrosine hydroxylase activity. However, this
      decrease in the activity of tyrosine hydroxylase was followed by an increase on
      the tenth day. These results allow us to conclude that perinatal exposure to
      cannabinoids produces changes in the normal development of several indices of the
      activity of dopaminergic neurons in the brain area containing the most important
      population of dopaminergic endings. These changes were mainly observed in males.
      They could be responsible for a long-term alteration in the neurological
      processes in which these neurons are involved in the adult.

PMID- 1350100
TI  - Dopaminergic influences on male sexual behavior of rhesus monkeys: effects of
      dopamine agonists.
AB  - Previous research has demonstrated that the mixed D1/D2 dopamine receptor
      agonist, apomorphine, and the specific D2 dopamine receptor agonist, quinelorane,
      facilitated penile erections and masturbatory behavior of male rhesus monkeys
      when they were tested in the presence of a female monkey that they could see,
      hear, and smell but not physically contact. The present study was designed to
      further examine dopaminergic influences on male sexual behavior of rhesus monkeys
      by evaluating male copulatory behavior following administration of these
      dopaminergic agents, as well as a D1 agonist, CY 208-243. Apomorphine and
      quinelorane treatment produced dose-dependent effects on male sexual responding.
      Compared to vehicle-based performance, postejaculatory intervals were shortened
      following treatment with either 100-200 micrograms/kg apomorphine or 2.5-10
      micrograms/kg quinelorane. Higher doses of apomorphine or quinelorane did not
      reliably influence the postejaculatory interval. Ejaculation latency,
      intromission frequency, and number of thrusts/intromission increased following
      administration of 200-400 micrograms/kg apomorphine and 25 micrograms/kg
      quinelorane, indicating that dopaminergic stimulation in this dose range raised
      the monkeys' ejaculatory threshold. No behavioral effects of the D1 agonist, CY
      208-243, were observed in this testing situation. These experiments provide
      further evidence that dopaminergic mechanisms may play a role in the regulation
      of male sexual behavior of rhesus monkeys and, in particular, demonstrate that
      the direction of the effect depends on the dopamine receptor subtype and dosage
      of the dopamine agonist being administered.

PMID- 1350101
TI  - Effect of a new anxiolytic, DN-2327, on learning and memory in rats.
AB  - The effects of a new anxiolytic, (2-(7-chloro-1,8-naphthyridin-2-yl)-3- [(1,4
      dioxa-8-azaspiro[4.5]dec-8-yl)-carbonylmethyl] isoindolin-1-one (DN-2327), on the
      execution of step-through passive avoidance and delayed spontaneous alternation
      tasks were assessed and compared with those of diazepam (DZP) and buspirone. DN
      2327 and buspirone (both 10 and 20 mg/kg, PO) impaired performance in the 48-h
      passive avoidance recall test when given prior to the test session, but not when
      given before the training trial. DZP impaired the performance at doses of more
      than 5 and more than 10 mg/kg PO when given prior to the test session and when
      given before the training trial, respectively. The action of DZP (10 mg/kg PO)
      when given before the training trial was antagonized by flumazenil (20 mg/kg, IP)
      and tended to be antagonized by DN-2327 (10 and 30 mg/kg, PO), but was not
      affected by buspirone. No evidence for possible amnesic effects of DN-2327 or
      buspirone on working memory was found in the delayed spontaneous alternation
      task, but DZP (3 and 10 mg/kg, PO) caused significant impairment of working
      memory. Electroshock sensitivities detected by flinch, jump, and vocalization
      thresholds were not influenced significantly by DN-2327 (30 and 100 mg/kg, PO),
      DZP (10 and 30 mg/kg, PO) or buspirone (30 and 100 mg/kg, PO).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1350103
TI  - Transglutaminase activity in human brain tumors.
AB  - Transglutaminase (TG) activity was measured in tissue samples of 45 human brain
      tumors (pituitary adenomas, meningiomas and gliomas) obtained during
      neurosurgery. Biochemical analysis and histopathological classification were
      carried out in the same samples. Mean enzyme activity was highest in non-glial
      tumors, but due to a high variability of values no significant changes were found
      between the various histological groups. Thus, TG activity, although considered
      to play a role in neoplastic growth, does not represent a biochemical marker of
      malignancy in human brain tumors.

PMID- 1350102
TI  - Atipamezole, an alpha 2 antagonist, stabilizes age-related high-voltage spindle
      and passive avoidance defects.
AB  - The present study investigates the effects of an alpha 2 antagonist, atipamezole
      (Ati), on the high-voltage spindle (HVS; Ati at 0.1, 1.0, and 3.0 mg/kg)
      activity, passive avoidance retention (PA; Ati at 3 mg/kg; injected before
      retention trial), and water maze (WM; Ati at 3 mg/kg; injected after daily
      training trials) acquisition of young and aged rats. PA retention trial
      performance defect of aged rats was partially alleviated by Ati at a 3-mg/kg
      dose. Ati at 3 mg/kg had no effect on the PA performance of young rats. Retention
      trial performance of nonshocked young or aged rats was not altered by a 3-mg/kg
      Ati dose. WM acquisition was not affected by posttraining Ati injections. Age
      related increase of HVS was stabilized by Ati at 1 or 3 mg/kg. Ati at 1 and 3
      mg/kg completely suppressed HVS of young rats. Ati at 0.1 mg/kg had no effect on
      HVS of young or aged rats. The results suggest that alpha 2-antagonist
      administration-induced increase in noradrenergic activity may stabilize age
      related HVS activity increase and PA performance defect.

PMID- 1350104
TI  - Is it still adequate to study the nervous system using methods of catalytic
      enzyme histochemistry?
AB  - The frequent use of methods different from enzyme histochemistry evokes the
      question, whether it is still useful to apply methods of catalytic enzyme
      histochemistry to study the nervous system. In this brief overview it is shown,
      that catalytic enzyme histochemistry can still contribute to a better
      understanding of nervous system function. This was enabled by methodological
      progress, i.e., the modification of already existing procedures or the
      development of new techniques for the visualization and measurement of enzymes in
      tissue sections using their catalytic properties. The methods for
      acetylcholinesterase, monoamine oxidase as well as certain exoglycosidases and
      phosphatases will be given as examples. The application of these procedures as
      well as of methods for proteases, oxyradical-generating oxidases and enzymes
      involved in the metabolism of amino acid and other transmitters will illustrate,
      that qualitative (localization) and quantitative (measurement) catalytic enzyme
      histochemistry can still contribute to a better understanding of nervous system
      function.

PMID- 1350105
TI  - Pertussis toxin non-sensitive G protein mediates cholinergic stimulation for
      secretion of pancreastatin and somatostatin from QGP-1N cells.
AB  - To clarify the possible role of a guanine nucleotide-binding protein (G-protein)
      in the signal transducing system activated by carbachol, actions of carbachol on
      human pancreastatin producing cell line (QGP-1N) were compared with those of
      fluoride, a well-known activator of stimulatory (Gs) or inhibitory (Gi) G
      protein. 10(-5) M of carbachol as well as 20 mM of NaF stimulated secretion of
      pancreastatin and somatostatin and intracellular Ca2+ mobilization. These
      secretion and Ca2+ mobilization were not modified by pertussis toxin, an
      inhibitor of Gi protein. These results suggest that pancreastatin and
      somatostatin secretions from QGP-1N are regulated by acetylcholine through a
      muscarinic receptor coupled to the activation of polyphosphoinositide breakdown
      by a G protein, which appears to be fluoride sensitive but is other than a Gi
      like protein.

PMID- 1350106
TI  - The source of calcium for CCK-induced contraction of the guinea-pig gall bladder.
AB  - The sources of calcium for cholecystokinin octapeptide (CCK-OP)-induced
      gallbladder smooth muscle contraction are considered both extracellular and
      intracellular, but the relative need for intracellular calcium especially at low,
      physiological concentrations is not clear. To better define the calcium sources
      responsible for guinea-pig gallbladder contractions in vitro, we inhibited
      calcium influx using the calcium channel blocker, methoxyverapamil, and a calcium
      free Krebs' solution. Availability and release of intracellular calcium stores
      were depleted by strontium substitution and ryanodine. CCK-OP was compared to
      bethanechol and potassium chloride (KCl). Preventing calcium influx with 10(-5) M
      methoxyverapamil depressed the responses to CCK-OP, bethanechol and KCl.
      Methoxyverapamil, however, had little effect on the time-dependent generation of
      tension to CCK-OP, but significantly reduced the response to bethanechol and KCl,
      each at ED50. The duration of the contractile response in the calcium-free Krebs'
      solution to CCK-OP was longer than that for bethanechol. Strontium (2.5 mM)
      significantly attenuated the response to CCK-OP and bethanechol, but not to KCl.
      Ryanodine significantly reduced contractions induced by CCK-OP but not for
      bethanechol, both at low dose ED25. These results indicate that contraction of
      the guinea-pig gallbladder induced by CCK-OP, bethanechol and KCl requires
      extracellular calcium influx. Further, the initiation and maintenance of
      contraction by CCK-OP and bethanechol necessitates calcium mobilisation from
      intracellular stores. CCK-OP may have a greater penchant for these calcium
      stores, particularly at physiological doses.

PMID- 1350107
TI  - Analysis of pokeweed mitogen-induced in vitro proliferative and antibody
      responses of bovine lymphocytes.
AB  - The functional role of subpopulations of bovine cells in the regulation of
      pokeweed mitogen (PWM)-induced proliferative and antibody responses of peripheral
      blood mononuclear cells (PBM) was analysed. Subpopulations of bovine PBM
      identified by specific monoclonal antibodies (mAbs) were isolated by sorting them
      through the fluorescence activated cells sorter (FACS). The depletion from PBM of
      T cells bearing the CD4 marker, recognised by mAb IL-A12, resulted in a reduction
      of PWM-induced responses, which could be partly reversed by the addition of CD4
      positive T cells. The depletion of cells belonging to the macrophage/monocyte
      lineage also resulted in a reduction of PWM-induced proliferative responses. PBM
      depleted of CD8 positive T cells, recognised by mAb IL-A51, showed increased PWM
      induced responses, which in turn were reduced by the addition of mAb IL-A51
      positive cells. Proliferative and antibody responses were also obtained by PWM
      stimulation of FACS-purified B cells, in the presence of bovine T cell growth
      factor.

PMID- 1350108
TI  - Multiple intestinal neoplasia caused by a mutation in the murine homolog of the
      APC gene.
AB  - Germ-line mutations of the APC gene are responsible for familial adenomatous
      polyposis (FAP), an autosomal dominantly inherited disease in humans. Patients
      with FAP develop multiple benign colorectal tumors. Recently, a mouse lineage
      that exhibits an autosomal dominantly inherited predisposition to multiple
      intestinal neoplasia (Min) was described. Linkage analysis showed that the murine
      homolog of the APC gene (mApc) was tightly linked to the Min locus. Sequence
      comparison of mApc between normal and Min-affected mice identified a nonsense
      mutation, which cosegregated with the Min phenotype. This mutation is analogous
      to those found in FAP kindreds and in sporadic colorectal cancers.

PMID- 1350109
TI  - Microdomains of high calcium concentration in a presynaptic terminal.
AB  - Increases in intracellular calcium concentration are required for the release of
      neurotransmitter from presynaptic terminals in all neurons. However, the
      mechanism by which calcium exerts its effect is not known. A low-sensitivity
      calcium-dependent photoprotein (n-aequorin-J) was injected into the presynaptic
      terminal of the giant squid synapse to selectively detect high calcium
      concentration microdomains. During transmitter release, light emission occurred
      at specific points or quantum emission domains that remained in the same place
      during protracted stimulation. Intracellular calcium concentration microdomains
      on the order of 200 to 300 micromolar occur against the cytoplasmic surface of
      the plasmalemma during transmitter secretion, supporting the view that the
      synaptic vesicular fusion responsible for transmitter release is triggered by the
      activation of a low-affinity calcium-binding site at the active zone.

PMID- 1350110
TI  - [The III National Congress of Hospital Hygiene].

PMID- 1350111
TI  - Contribution of the amygdala and nucleus accumbens to ventral pallidal responses
      to dopamine agonists.
AB  - Neurons recorded from ventral pallidum/substantia innominata (VP) of the basal
      forebrain respond to dopaminergic agonists that activate either the D1 or D2 the
      receptor subtype. Major afferent systems to the VP originate within amygdaloid
      nuclei (AMN) and the nucleus accumbens (NA). Since both the AMN and the NA are
      dopaminoceptive, the present study sought to analyze the contribution of these
      afferent systems to VP responses to dopaminergic agonists. Single VP neurons were
      electrophysiologically recorded in vivo from chloral hydrate-anesthetized rats,
      and the following determinations were made. 1) Effects of pharmacologic
      inactivation of an afferent system were assessed by monitoring VP neurons during
      intracerebral microinjections of the local anesthetic procaine, administered
      directly into either the AMN or the NA. 2) With procaine-induced VP rate changes
      used to indicate an afferent influence on the recorded neuron, VP responses to
      apomorphine (an agonist that acts at D1 and D2 receptor subtypes), SKF38393 (a D1
      agonist), or quinpirole (a D2 agonist) were determined and compared with
      responses in rats not receiving the procaine pretreatment. Following
      pharmacologic inactivation of either the AMN or the NA, approximately 80% of the
      VP neurons monitored demonstrated rate changes, illustrating that spontaneous
      neuronal firing in the Vp is dependent on tonically input systems. Following
      afferent cessation, responses to apomorphine and quinpirole remained intact,
      suggesting that the AMN or NA is not necessary for VP responding to the systemic
      administration of dopaminergic agonists that act at D2 receptors. In contrast,
      the number of neurons that responded to SKF38393 was diminished follow intra-AMN
      (but not intra-NA) procaine. This suggests that D1-induced VP responses are
      mediated, at least in part, via the AMN.

PMID- 1350112
TI  - Modulation of single-unit activity in the rat medial amygdala by
      neurotransmitters, estrogen priming, and synaptic inputs from the hypothalamus
      and midbrain.
AB  - The medial amygdala (m-AMG) appears to act as an integrative center for sensory,
      synaptic, and endocrine signals important in the regulation of reproductive
      function. Extracellular single-unit recordings from anesthetized, ovariectomized
      female rats were used to investigate neuropharmacological, hormonal, and synaptic
      modulation of neurons in the m-AMG. Electrical stimulation of the ventromedial
      hypothalamus (VMH) elicited excitatory or inhibitory orthodromic responses in 72%
      and antidromic responses in 7% of m-AMG neurons, whereas stimulation of the
      midbrain central gray (MCG) induced orthodromic responses in 43% of m-AMG
      neurons. Interestingly, most cells that were influenced by MCG stimulation were
      also orthodromically driven by the VMH, as 40% of all m-AMG cells responded
      orthodromically to both the VMH and MCG. Furthermore, the majority of these cells
      tended to be modulated by both areas in the same direction. Iontophoretic
      application of glutamate, GABA, ACh, and LHRH could modulate the spontaneous
      firing rate of m-AMG neurons. In particular, ACh had a predominantly excitatory
      action, which was more effective on m-AMG neurons that were orthodromically
      driven by the VMH and that were from estrogen-primed animals. In addition to
      increasing chemical responsiveness to ACh, estrogen priming of ovariectomized
      animals also increased the spontaneous firing rate of m-AMG neurons and decreased
      the number of silent cells. These modulatory actions on m-AMG neurons may be
      important in the medial amygdala's regulation of the behavioral and endocrine
      aspects of reproductive function in the female rat.

PMID- 1350113
TI  - Effect of various neurotransmitters and neuropeptides on the release of
      corticotropin-releasing hormone from the rat cortex in vitro.
AB  - Corticotropin-releasing hormone (CRH), in addition to its neuroendocrine role,
      may act as a central neurotransmitter. Cerebral cortical CRH may have an
      important role in behavioral and neurodegenerative disorders. To gain an
      understanding of factors that may influence cortical CRH, we investigated the
      effect of several neurotransmitters and neuropeptides on the release of
      immunoreactive CRH (iCRH) from various cerebral cortical regions [frontal (FC),
      parietal (PC), temporal (TC), and occipital (OC)] in vitro. The hypothalamic
      release of iCRH was also evaluated under the same experimental conditions. Basal
      release of iCRH was approximately 2-fold, and KCl-stimulated iCRH release was
      approximately 4-fold higher in the hypothalamus than in any of the cortical
      regions. Cortical iCRH release was stimulated by 10 nM somatostatin (SRIF) in PC
      and 1 nM neuropeptide Y (NPY) in TC. Cortical iCRH release was inhibited by 1 and
      10 nM acetylcholine (ACh), 0.1 microM glutamate, and 10 nM NPY. These effects
      were confined to the FC and/or PC. Hypothalamic iCRH release was stimulated by 1
      and 10 nM ACh, 10 microM GABA, and 1 and 10 nM serotonin but was inhibited by 10
      nM SRIF and 1 microM GABA. Growth hormone-releasing hormone did not affect
      cortical or hypothalamic iCRH release. These results demonstrate that CRH release
      from the cerebral cortex and the hypothalamus are under different regulatory
      mechanism(s). Furthermore, they indicate that the release of CRH in various
      cortical regions may be regulated differentially by the same neurotransmitter.

PMID- 1350114
TI  - Criteria for judging the relative toxicity of chemicals from developmental
      toxicity data: a workshop summary.
AB  - In summary, participants of this workshop confirmed that many criteria need to be
      considered when interpreting the results of developmental toxicity studies. All
      aspects of developmental toxicity are of interest, but their importance to the
      consideration varies along the continuum from hazard detection to risk
      estimation. As with many other manifestations of toxicity, potential
      developmental risk to humans is a function of exposure and developmental
      toxicity, the latter reflecting the inherent potential of a substance to cause an
      adverse effect under some defined condition. All of the criteria discussed in
      this workshop were considered to be of some importance in characterizing the
      developmental toxicity of a substance, their relative importance being a function
      of the question under consideration. Proper interpretation of developmental
      toxicity data, which must include prenatal as well as postnatal observations to
      be considered complete, should take into account the differential toxicity to the
      mother and the conceptus, the nature of the developmental toxicity observed, and
      the consistency of response between species. The proximity of human exposure
      levels to dose levels that are developmentally toxic in animals is a major
      determinant of the potential for hazard to humans. Mechanistic and
      pharmacokinetic knowledge can modulate interpretation of descriptive data and
      refine the prediction of human hazard. Recognizing that in vitro studies will
      never completely recapitulate the results of in vivo studies, the committee to
      update the "Smith list" will move forward taking the discussions of this workshop
      into account.

PMID- 1350116
TI  - Proceedings Voorjaarsdagen 1992.

PMID- 1350115
TI  - Muscle relaxation with Norcuron in patients undergoing obstetrical-gynaecological
      operation.
AB  - The observations with Norcuron (Richter) injection used for muscle relaxation in
      the course of 204 obstetrical-gynaecological operations have been discussed. In
      the majority of cases Caesarean section was performed, the other interventions
      were major operations. Norcuron proved to be a neuro-muscular blocking agent
      which has no cardiovascular side-effects, has a medium duration of action, and
      may be repeatedly administered according to requirement without risk of
      cumulation. It may be combined with other anaesthetics, its action may be
      successfully antagonized, and the drug has no postoperative after-effects. The
      Apgar scores of the newborns remained within the normal ranges.

PMID- 1350117
TI  - Transfection with gamma-glutamyl transpeptidase enhances recovery from
      glutathione depletion using extracellular glutathione.
AB  - Glutathione (L-gamma-glutamyl-L-cysteinylglycine) is an important constituent of
      the antioxidant and detoxifying mechanisms of cells. The plasma membrane bound
      enzyme, gamma-glutamyl transpeptidase (GGT), catalyzes the first step in the
      degradation of extracellular glutathione, the components of which are then used
      for de novo glutathione synthesis. We tested the hypothesis that an increase in
      GGT activity would enhance the utilization of extracellular glutathione by cells
      challenged with a glutathione-depleting agent. A eukaryotic system stably
      overexpressing GGT (nearly 200-fold) was developed by transfection of NIH-3T3
      fibroblasts with a human placental GGT cDNA. These cells and controls were
      incubated for 30 min with 1 mM diethyl maleate, which caused approximately 80%
      intracellular glutathione depletion. Glutathione was added to the medium and
      cells were allowed to resynthesize intracellular glutathione. The transfected
      cells used extracellular glutathione much more efficiently than controls in terms
      of both the concentration dependence and the rate of glutathione resynthesis.
      Serine-borate, a competitive inhibitor of GGT, blocked the restoration of
      intracellular glutathione. The results support the hypothesis that the increase
      in GGT activity that occurs in some toxicologic or pathologic conditions could
      provide protection against glutathione depletion.

PMID- 1350118
TI  - Two polyhydroxylated steroids from the Chinese soft coral Sinularia microclavata.
AB  - Two polyhydroxylated steroids have been isolated from the South China Sea soft
      coral Sinularia microclavata, and their structures were established as 24
      methylenecholestane-1 alpha,3 beta,5 alpha,6 beta-tetrol and 1 alpha,3 beta,5
      alpha-trihydroxy-24-methylenecholestan-6-one from spectral evidence and from
      comparison with two reference compounds, numersterol A and 24-methylenecholestane
      1 alpha,3 beta,5 alpha,6 beta, 25-pentol, which were isolated from the soft
      corals, Simularia numerosa and Sarcophyton glaucum, respectively.

PMID- 1350119
TI  - Physician's assistants: a missing link.

PMID- 1350120
TI  - A new generation of blood components.

PMID- 1350121
TI  - The cellular and molecular basis of the platelet storage lesion: a symposium
      summary.

PMID- 1350122
TI  - Advantages and guidelines for using alpha-2 agonists as anesthetic adjuvants.
AB  - Xylazine and medetomidine produce reliable sedation, muscle relaxation, and
      analgesia in dogs and cats. In addition, alpha-2 agonists have proved very
      effective as sedative-analgesic adjuncts when coadministered with benzodiazepine
      or opioid agonists. Alpha-2 agonists should not be classified as monoanesthetics.
      They are excellent anesthetic adjuncts when combined with dissociatives and
      opioids. Because of the acute alterations in cardiopulmonary function commonly
      induced by alpha-2 agonists, it is suggested that their use be restricted to the
      young healthy patient undergoing routine surgical or diagnostic procedure. The
      development of more specific and selective alpha-2 agonists will continue to
      enhance the safety and reliability of this novel class of compounds. The unique
      spectrum of anesthetic properties induced by alpha-2 agonists has assured them of
      an increasingly prominent role in the development of new and sophisticated ways
      of achieving anesthesia.

PMID- 1350123
TI  - Precautions when using alpha-2 agonists as anesthetics or anesthetic adjuvants.
AB  - Alpha-2 adrenergic agonists have some unique properties that could theoretically
      make them useful in the perianesthetic period: they reduce the MAC of inhaled
      anesthetics, and they are reversible. They also have properties that may limit
      their usefulness, such as marked decreases in cardiac output. Their clinical
      utility awaits further studies.

PMID- 1350124
TI  - Neuromuscular blocking agents.

PMID- 1350125
TI  - Anatomy of the spinal cord and how the spinal cord is affected by local
      anesthetics and other drugs.
AB  - The spinal cord can be affected by several categories of drugs: local
      anesthetics, opiate agonist, alpha 2 adrenergic agonists, and ketamine. The
      mechanism of action, side effects, and usefulness of these injections vary with
      the type of drug used.

PMID- 1350126
TI  - Absence of selection of HIV-1 variants in vivo based on
      transcription/transactivation during progression to AIDS.
AB  - The activity of the human immunodeficiency virus type 1 (HIV-1) transactivation
      protagonists tat and TAR has been analyzed from sequential primary material. The
      sequences were amplified from uncultured peripheral blood mononuclear cells.
      Despite fluctuations within the tat and TAR quasispecies there was no obvious
      selection for a variant encoding more powerful transactivation components either
      in vivo or ex vivo, indicating that this system is not exploited during disease
      progression. The basal levels of the natural promoters were, depending on the
      cell line, two- to fourfold higher than that of the reference promoter, itself
      derived from ex vivo adapted HIV-1 Lai.

PMID- 1350127
TI  - Protective role of cytotoxic lymphocytes against murine leukemia virus-induced
      neurologic disease and immunodeficiency is enhanced by the presence of helper T
      cells.
AB  - We examined the role of T cells and their separated subsets in providing immunity
      against ts1 (a mutant of the Moloney murine leukemia virus) induced paralysis and
      immunodeficiency. Adoptive transfer of syngeneic total T cells from immunized
      mice protected newborn mice, at least partially, from ts1-induced disease
      syndrome. In infected mice who received total immune T cells, virus replication
      was reduced and the mice survived longer. When only separated immune CD8+ T cells
      were transferred to infected mice, similar protection, albeit to a lesser extent,
      was observed. Transfer of separated immune CD4+ T cells alone gave no protection.
      However, when recombined CD4+ and CD8+ cells were transferred together, an immune
      response similar to that when total T cells were transferred was observed.
      Cytotoxic assays from ts1-immunized mice revealed the presence of virus-specific
      CD8+ cytotoxic T lymphocytes that could lyse virus-expressing cells at a high
      effector/target ratio. We conclude that CD8+ T cells alone can provide immunity
      against ts1-induced paralysis and immunodeficiency and that the simultaneous
      presence of CD4+ T cells can also significantly enhance the immune response.

PMID- 1350128
TI  - [The molecular mechanisms regulating the functional activity of the calcium
      channels in heart muscle cells].

PMID- 1350131
TI  - Werner's syndrome: no difference in in vitro life span of dermal fibroblasts from
      proximal and distal parts of the body.
AB  - Recently it has been reported that fibroblasts from distal parts of the body of a
      patient with Werner's syndrome grew poorly in vitro as compared with those from
      the proximal part of the same patient. To confirm this observation, cultures of
      fibroblasts from different parts of the body were set up in 2 cases of Werner's
      syndrome, but no significant difference in life span was observed. Fetal calf
      serum (FCS) and fibroblast growth factor (FGF) stimulated growth of fibroblasts
      from different body parts equally well. These data indicate that there is no
      difference in growth activity of fibroblasts from proximal and distal body parts
      in patients with Werner's syndrome. Moreover, the growth rate of epidermal
      outgrowths did not differ significantly between proximal and distal parts of
      these patients.

PMID- 1350130
TI  - Candida albicans grown in glucose-free media contains serum-independent
      chemotactic activity.
AB  - Infection of skin with Candida albicans is usually followed by infiltration of
      neutrophil granulocytes (PMN). So far, chemotaxins for PMN have been isolated
      from C. albicans cultures grown in the presence of glucose. However, since
      glucose is not present in skin in vivo, a contribution of such factors to Candida
      triggered cutaneous inflammation would appear unlikely. In order to clarify this
      question, chemotactic activity was measured in extracts from three different
      strains of C. albicans which were grown in five different peptone media free of
      carbohydrates and serum. In addition, four culture systems were supplemented with
      lipids normally present in human stratum corneum, including a triglyceride,
      cholesterol, and sphingomyelin. In all sugar-free grown cultures, serum
      independent chemotactic activity was detected by use of the Boyden chamber
      technique. Since, as shown here in vitro, production of neutrophil chemotaxins by
      C. albicans is independent of glucose-feeding, a possible role of Candida
      chemotaxins in the pathophysiology of cutaneous candidosis can no longer be
      excluded.

PMID- 1350129
TI  - [C-erbB-2 oncogene amplification in breast cancer in correlation to steroid and
      epidermal growth factor receptor].
AB  - The amplification grade of oncogene c-erbB-2 was examined by the polymerase-chain
      reaction-method in DNA's of 56 primary mammary carcinomas. 26 (46.4%) of these
      showed the amplified oncogene c-erbB-2. In the strongly amplified cases, the
      expression of the c-erbB-2 oncoprotein was verifiable immunohistochemically.
      Between the progesterone receptor status (PR) and the amplified c-erbB-2 oncogene
      there was a statistically proven dependency. No correlation was observed between
      the amplified c-erbB-2 oncogene and the epidermal growth-factor receptor (EGFR).

PMID- 1350132
TI  - A comparison of morphoea and lichen sclerosus et atrophicus in vitro: the effects
      of para-aminobenzoate on skin fibroblasts.
AB  - To study the effects of para-aminobenzoate on the dermis, fibroblast cell lines
      derived from lesions of lichen sclerosus et atrophicus, from morphoea and from
      normal skin were incubated with Potaba in vitro. Monolayer cultures containing
      Potaba showed a dose-dependent inhibition of proliferation beginning at 1,000
      micrograms/ml with total inhibition at 10,000 micrograms/ml. Mean ID50 values for
      the three groups were not significantly different. There was a similar dose
      dependent inhibition of glycosaminoglycan secretion in all 3 groups, except at
      10,000 micrograms/ml where secretion by lichen sclerosus et atrophicus and
      morphoea fibroblasts was significantly more inhibited than normal lines.
      Inhibition of the glycosaminoglycan secretion at 10-1,000 micrograms/ml was a
      direct effect of the drug rather than an indirect effect of changes in cell
      density, and lichen sclerosus et atrophicus fibroblasts produced about 40% more
      GAG than the morphoea or normal lines growing at similar densities. Collagen
      synthesis was increased in both lichen sclerosus et atrophicus and morphoea cell
      lines, with increased non-collagenous protein in morphoea lines. These results
      confirm that there are differences between lichen sclerosus et atrophicus and
      morphoea, and suggest glycosaminoglycan secretion as a possible target for the
      therapeutic action of Potaba.

PMID- 1350133
TI  - Hypertrichosis lanuginosa acquisita.
AB  - Hypertrichosis lanuginosa acquisita was observed in a female patient with stage
      IV malignant melanoma and also diffuse melanosis of the skin. The patient died
      within 2 months after the appearance of HL.

PMID- 1350134
TI  - Extraocular sebaceous carcinoma.
AB  - A 79-year-old man with no history of previous irradiation presented with a large
      ulcerated tumour of the cheek. The histological features favoured a true
      sebaceous carcinoma. Neither squamous nor basal differentiation were seen. Sudan
      stainings were positive. Tumour cells expressed suprabasal keratins and were
      negative for carcinoembryonic antigen, vimentin and S 100 protein. Extraocular
      sebaceous carcinomas occurring without previous irradiation are rare tumours
      which behave aggressively. Treatment regimens are discussed.

PMID- 1350135
TI  - Schnitzler's syndrome (urticaria and macroglobulinemia) associated with
      pseudoxanthoma elasticum.
AB  - Schnitzler's syndrome, first described in 1974, is defined by chronic non
      pruritic urticaria, osteocondentation, and a monoclonal IgM dysproteinemia, but
      without criteria of lymphoproliferative disease. We report a patient with chronic
      urticaria and macroglobulinemia. In addition, he had double monoconal
      dysproteinemia IgM kappa (31.3 g/l) and IgA lambda, osteocondensation, and some
      cutaneous lesions of pseudoxanthoma elasticum. Only 20 cases of Schnitzler's
      syndrome have been reported hitherto. This is the first case associated with
      pseudoxanthoma elasticum, which was localized and discovered at the same time as
      Schnitzler's syndrome. We discuss the possible role of monoclonal immunoglobulin
      in the occurrence of localized elastorrexhis.

PMID- 1350136
TI  - Coeliac-type dental enamel defects in patients with dermatitis herpetiformis.
AB  - The teeth of 30 adult patients with dermatitis herpetiformis and 66 sex- and age
      matched healthy controls were examined for dental enamel defects. Sixteen of the
      patients (53%) with dermatitis herpetiformis, opposed to only one (2%) of the
      healthy controls (p less than 0.001), were found to have coeliactype permanent
      tooth enamel defects. The grades of these defects were milder than those
      described for severe coeliac disease. There was no correlation between the degree
      of enamel defects and jejunal villous atrophy. The present finding of frequent
      coeliactype dental enamel defects in adults with dermatitis herpetiformis
      suggests that these patients were already suffering from subclinical
      gluteninduced enteropathy in early childhood, at the time when the crowns of
      permanent teeth develop.

PMID- 1350137
TI  - Clinical and non-invasive evaluation of 12% ammonium lactate emulsion for the
      treatment of dry skin in atopic and non-atopic subjects.
AB  - Clinical dryness of the leg skin is a common problem among dermatological
      patients. The efficacy and safety of 12% ammonium lactate emulsion (Keratisdin)
      for the treatment of dry skin on the legs of atopic and non-atopic subjects has
      been assessed by clinical criteria and by five different non-invasive methods.
      These methods measure biophysical parameters such as electrical capacitance of
      stratum corneum, skin surface lipids, transepidermal water loss (TEWL), skin
      surface topography (scanning electron microscopy and image analysis) as well as
      the biomechanical properties of the skin. Treatment with the test emulsion
      significantly reduced the severity scores for dryness, desquamation and pruritus
      when measured 15 days later. All patients tested showed a significant increase in
      electrical capacitance, skin surface lipids, extensibility and firmness of the
      skin, and an improvement in the skin barrier function and skin surface
      topography. This study showed that non-invasive techniques are excellent
      complementary tools in clinical studies.

PMID- 1350138
TI  - The in vivo effect of UVB radiation on skin bacteria in patients with atopic
      dermatitis.
AB  - Fourteen patients suffering from atopic dermatitis under treatment with UVB
      radiation were subjected to aerobic bacterial cultures in order to investigate
      whether this ultraviolet waveband has any in vivo germicidal effects, and, if so,
      whether there is a correlation with clinical improvement. Treatments were given 3
      times a week for 8 weeks. Bacterial samples were collected before, midway and
      after the termination of therapy. On the latter two occasions, cultures were
      performed 30 min and 24 h post-UVB irradiation. The main bacteria found were
      Staphylococcus epidermidis and S. aureus. S. aureus carriage was found in 12
      patients in lesional, dermatitic skin, and in 11 patients in clinically non
      lesional skin. UVB radiation was found to have an antimicrobial effect primarily
      concerning S. aureus. Bacterial counts of this organism in lesional skin were
      decreased from a mean of 1.3 x 10(3) to 1.2 x 10(1) bacteria per cm2 skin at the
      8-week 30-min count (p less than 0.01) and 7.5 x 10(1) at the 8-week 24-h count
      (p less than 0.05). The treatment yielded a statistically significant clinical
      improvement.

PMID- 1350139
TI  - Atypical presentation of co-existent Haemophilus ducreyi and Treponema pallidum
      infection in an HIV-positive male.
AB  - A 25-year-old homosexual black male presented with asymmetrical perianal
      ulceration of uncertain clinical origin. Indepth microbiological examination
      revealed the combined presence of Haemophilus ducreyi and Treponema pallidum. The
      atypical clinical appearance may have been due to the changed immunological
      status of the host's being infected with Human Immunodeficiency Virus.

PMID- 1350142
TI  - Lichen planus: an unusual cause of phimosis.
AB  - We report on a 47-year-old man with oral and genital lichen planus. After some
      months of the disease, increasing phimosis developed which had not been present
      before. Retraction of the foreskin was now impossible and sexual intercourse was
      painful. Treatment with triamcinoloneacetonide and etretinate ameliorated the
      phimosis but the patient was still not comfortable and circumcision was
      performed. Histology from the foreskin revealed the typical picture of lichen
      planus. No features of lichen sclerosus et atrophicus were present. This is the
      first published observation of phimosis as a result of lichen planus.

PMID- 1350141
TI  - Transepidermal water loss related to volar forearm sites in humans.
AB  - The aim of this study was to demonstrate differences in human skin transepidermal
      water loss (TEWL) in vivo related to site on volar forearm. Fourteen healthy
      volunteers entered the study and seven sites were tested. After randomization of
      both forearm and measure order, TEWL measurements were performed using the Servo
      Med Evaporimeter. TEWL values next to the wrist were found statistically greater
      than on the other sites. Hence wrist region should preferably be excluded from
      TEWL measurements on forearm.

PMID- 1350140
TI  - Non-specific immunity in patients with primary anogenital warts treated with
      interferon alpha plus cryotherapy or cryotherapy alone.
AB  - Combination treatment of primary anogenital warts with subcutaneous interferon
      alpha 2a plus cryotherapy was no more efficacious than cryotherapy alone.
      Patients with primary AG warts showed no in vitro or in vivo suppression of non
      specific immunity. In patients treated with interferon plus cryotherapy non
      specific cellular immunity was stimulated, both in vitro and in vivo compared
      with patients treated with cryotherapy alone.

PMID- 1350143
TI  - Moisturizers prevent irritant dermatitis.
AB  - The purpose of this study was to investigate the ability of eight different
      moisturizers to prevent irritant dermatitis. Twelve healthy female students
      washed the outer aspect of their upper arms with a liquid detergent for one
      minute twice a day for one week. Seven skin creams and one skin oil were applied
      to 3 x 7 cm areas of the left upper arm just after each washing, while the right
      upper arm was left untreated. Transepidermal water loss (TEWL) (mean) increased
      from 7.1 to 9.3 g/m2/h (p less than 0.001) and laser-Doppler flowmetry (LDF)
      value (mean) decreased from 11.8 to 10.8 arbitrary units (N.S.) in the left upper
      arm, but there was no statistical difference between the eight moisturizers.
      During the second week of the study, the test subjects did not continue washing
      their arms. Eight areas (3 x 7 cm) of the right upper arm were treated with the
      moisturizers twice a day. The mean TEWL value decreased from 20.3 to 8.6 (p less
      than 0.0011) over 7 days, but there were no significant differences between the
      individual moisturizers. The laser-Doppler values showed the same trend as the
      TEWL values. In conclusion, regular use of emollients prevented irritant
      dermatitis from a detergent.

PMID- 1350144
TI  - Nickel contact sensitivity in the guinea pig. An efficient open application test
      method.
AB  - Nickel contact sensitivity was successfully induced in guinea pigs using an open
      epicutaneous application method. Immediately after pretreatment with 1% aqueous
      sodium lauryl sulfate, upper back skin was treated daily for 4 weeks with 0.3%-3%
      nickel sulfate in either a 1% lanolin cream (Vaseline, pH 5 SAD creme) or
      hydroxypropyl cellulose. Weekly intradermal injections with aluminium potassium
      sulfate were used as adjuvant. The animals were challenged twice with a one week
      interval, with nickel sulfate 2% in water and 1% in petrolatum, respectively. The
      response rates in the test groups treated with nickel sulfate 1% or 3% in the
      lanolin cream or 1% in hydroxypropyl cellulose were significantly different from
      the response rate in the control group. Considering both readings at both
      challenges, the frequency of sensitization was 57-93% (8 of 14 to 13 of 14
      animals) in the group treated with 1% in the lanolin cream, 60-100% (9/15 to
      15/15 animals) in the group treated with 3% in the lanolin cream, and 67-75%
      (8/12 to 9/12 animals) in the group treated with 1% in hydroxypropyl cellulose.
      Rechallenge of initially sensitized animals 10 weeks later confirmed that a
      lasting contact allergy had been obtained.

PMID- 1350145
TI  - Drug-triggered pemphigus in a predisposed woman.
AB  - A 31-year-old woman with three pemphigus-prone antigens in her HLA haplotype (B7,
      DR4, DQw7) developed the disease soon after taking a pyrazolone derivative, viz.
      feprazone. The pemphigus lesions persisted despite withdrawal of the drug and
      worsened appreciably when she used ceftriaxone (a new cephalosporin with three
      sulphur atoms) for a bout of acute pharyngitis. Thiol groups formed from the
      metabolic breakdown of ceftriaxone are thought to have promoted acantholysis via
      a biochemical route. Genetic predisposition alone ('the soil') may be essential,
      though not per se sufficient for outbreak of pemphigus; the intervention of
      exogenous, heterogeneous factors ('the seed') often seems decisive in triggering
      full-blown disease.

PMID- 1350146
TI  - Bullous impetigo caused by group A streptococci. A case report.
AB  - Bullous impetigo is considered to be a staphylococcal disease. Staphylococcus
      aureus, phage type 71, produces an epidermolytic toxin, assumed to be the cause
      of bullous formation in the skin. We present a case of bullous impetigo.
      Microbiological tests suggested beta-hemolytic streptococci, group A, M-type 3,
      as the etiological agent. Group A streptococci were isolated from the throat of
      the patient's mother and brother. The strains were shown to be identical, by
      means of DNA-'fingerprinting' and M-typing.

PMID- 1350147
TI  - Morphometry in clinical dermatology.
AB  - Rapid and simple methods are presented which allow the estimation of areas, area
      fraction and contour lengths in clinical dermatology. They are based on point
      counting and intercept measurements using simple grids made on transparent film
      or on overhead foils. Because of their ease of use, these grids allow the
      determination of the size as well as the irregularity of skin lesions even during
      daily clinical work. The applications presented here include the area
      determination of naevi, leg ulcers, wheal and flare reactions and migration areas
      in lymphocyte and macrophage migration assays. Additionally, the determination of
      area fraction in psoriasis and sebutape evaluation is described. Other possible
      applications such as estimation or contour length, and determination of
      irregularity and estimation of the volume of tumours are discussed.

PMID- 1350148
TI  - Birthmarks in 4346 Finnish newborns.
AB  - We examined all babies born live (4346) at two Finnish hospitals in the course of
      one year to determine the frequency of birthmarks, specially pigmented lesions,
      among Finnish newborns. All birthmarks excluding common salmon patches on the
      forehead and neck were recorded and photographed at birth. The babies were re
      examined at the age of three months. Various birthmarks were recorded for 241 of
      4346 babies, i.e. for 5.5% of all newborns. Ninety-one (2.1%) infants had
      congenital pigmented skin lesions, 167 (3.8%) had various vascular lesions and 21
      (0.5%) had other birthmarks. The frequency of congenital melanocytic naevi was
      1.5%. Most of the naevi were less than 20 mm in diameter. Only one child had a
      giant naevus. The frequency of congenital naevi in our study was the same or
      somewhat higher than previously described (1-8) but fewer other pigmented skin
      lesions were found than in previous studies perhaps due to racial differences.

PMID- 1350149
TI  - Relapsing bullous staphyloderma.
AB  - Relapsing eruptions of bullae rapidly turning into pustules were seen in a 69
      year-old woman of good general health. At different times during several months
      of observation, strains of S. aureus were grown from various lesions, including
      one (phage group III) producing enterotoxin C. Systemic involvement except for
      high BSR was absent and repeated blood cultures were negative. Histopathological
      findings resembled impetigo. Antibiotic treatment was effective. As this disease
      does not fit into any of the well-known pustular infectious dermatoses, we
      suggest calling it relapsing bullous staphyloderma.

PMID- 1350150
TI  - Evaluation of port wine stain perfusion by laser Doppler imaging and thermography
      before and after argon laser treatment.
AB  - Thirteen patients with port wine stains (PWS) were treated with argon laser
      therapy. Before and at different points in time following treatment, skin blood
      perfusion and temperature were mapped with laser Doppler imaging and
      thermography. In nine patients no elevation in blood perfusion was observed in
      the PWS in comparison with the surrounding normal skin before treatment. In the
      remaining four patients a significantly (p less than 0.01) higher blood flow was
      recorded within the PWS. Immediately after treatment nine patients showed
      elevated perfusion within the PWS. During the first two days following treatment,
      all patients showed a gradually decreasing hyperperfusion in the borderline
      between the PWS lesion and surrounding skin. Immediately after treatment 10
      patients had a significantly (p less than 0.01) higher temperature in the PWS
      than in normal skin. During the first 24 h following treatment, an elevated
      perfusion was in general accompanied by a tissue temperature increase. Three and
      a half months after argon laser treatment, three patients showed excellent
      clinical results with no remaining PWS spots or scarring. Two of these patients
      had had both elevated perfusion and temperature in the PWS prior to treatment.

PMID- 1350151
TI  - Allogeneic cultured keratinocytes in the treatment of leg ulcers. A pilot study.
AB  - Forty-two patients (10 males and 32 females) with 52 chronic leg ulcers were
      treated with sheets of cultured allogeneic keratinocytes. Sixty-five % of the
      ulcers healed completely and the healing rate differed between various diagnostic
      groups. The best results were obtained in patients with venous ulcers and wounds
      with mixed etiology, whereas less improvement was observed with ischaemic ulcers.
      Rheumatic ulcers also responded well in combination with oral corticosteroids.
      The overall impression was that the grafting procedure markedly enhanced wound
      healing.

PMID- 1350152
TI  - A new micronized 5-methoxypsoralen preparation. Higher bioavailability and lower
      UVA dose requirement.
AB  - A new tablet of micronized 5-methoxypsoralen (5-MOP) and a commonly used tablet
      in therapy (Psoraderm 5) were compared in 12 healthy subjects. Each subject
      ingested 1.2 mg/kg body weight of each formulation on different days.
      Bioavailability and phototoxicity of 5-MOP were compared. The results showed that
      serum and suction blister concentrations were significantly higher and occurred
      earlier after the oral intake of the micronized preparation. A series of
      graduated UVA doses were administered, one dose each time the concentration serum
      peaked, in order to determine the minimum phototoxic dose for each formulation.
      The micronized preparation induced greater photosensitivity than the unmicronized
      one. The micronized 5-MOP tablet may thus allow lower doses of UVA to achieve
      therapeutic results in photochemotherapy and a shortened waiting period following
      ingestion of drug.

PMID- 1350153
TI  - Peptide T in the treatment of severe psoriasis.
AB  - We investigated the effect of treatment with peptide T on severe psoriasis in 5
      patients. Within 2 months, peptide T led to complete remission of all lesions in
      1 patient and to good improvement in 3 others. In 1 patient, no effect was
      observed.

PMID- 1350154
TI  - Successful treatment of chronic skin diseases with clobetasol propionate and a
      hydrocolloid occlusive dressing.
AB  - The lesions of 141 patients with chronic skin diseases unresponsive to therapy
      were treated once a week with clobetasol propionate lotion left under the
      completely occlusive patch Duoderm. In 131 patients the lesions resolved
      completely, while partial remission was observed in the remaining 10. The mean
      interval to complete remission was: for chronic plaque psoriasis, 12 days;
      psoriasis on palms and soles, 2.5 weeks; palmoplantar pustulosis, 2.2 weeks; skin
      lesions of Reiter's syndrome, 3 weeks; chronic lichenified eczema, 2.0 weeks;
      neurodermatitis, 3.1 weeks; breast eczema, 9 days; discoid lupus erythematosus,
      3.7 weeks; lichen planus, 2.8 weeks; sarcoidosis, 4 weeks; and lichen sclerosus
      et atrophicus, 2 weeks. Other conditions benefitting from the treatment were
      pompholyx, necrobiosis lipoidica, granuloma annulare and pretibial myxedema. The
      amount of topical corticosteroids needed was reduced to at most 1/20 and to as
      little as 1/100, compared with common topical steroid preparations.

PMID- 1350155
TI  - Anthralin is a potent inhibitor of pityrosporum orbiculare/ovale in vitro.
AB  - Two strains of Pityrosporum orbiculare/ovale were grown in a liquid medium and
      exposed to different concentrations of the imidazoles ketoconazole and
      clotrimazole as well as anthralin, liquor carbonis detergens and salicylic acid.
      With regard to growth inhibition of yeast cells, the efficacies of anthralin and
      the imidazoles were similar, a half-maximal inhibition being achieved with an
      anthralin concentration of 7 mg/l. Liquor carbonis detergens and salicylic acid
      also inhibited growth of Pityrosporum orbiculare/ovale, but only at much higher
      concentrations. The response to salicylic acid was mainly due to its acid pH.

PMID- 1350156
TI  - Treatment of pityriasis versicolor with a single dose of fluconazole.
AB  - Twenty-four patients with extensive or recurrent pityriasis versicolor were
      treated with a single oral dose of 400 mg of fluconazole. Twenty-three patients
      returned for follow up. Seventeen or 74%, were free of lesions 3 weeks after
      treatment and no recurrences were seen 6 weeks after treatment. The majority of
      the patients found the treatment effective, safe and convenient.

PMID- 1350157
TI  - Eeosinophils in allergic contact dermatitis.

PMID- 1350158
TI  - Growth inhibition of RPMI 8226 human myeloma cells by peripheral blood
      lymphocytes.
AB  - To clarify the components of cellular immunity responsible for defense against
      the clonal development of myeloma cells, we tested the capacity of human
      peripheral blood lymphocytes (PBLs) to inhibit the growth of 3 human myeloma cell
      lines (RPMI 8226, OPM-1, and OPM-2). RPMI 8226 was found to be sensitive to PBLs,
      showing almost complete growth arrest when cultured with PBLs for 72 h.
      Inhibition of the growth of RPMI 8226 cells required direct cell-to-cell contact
      but not presensitization of the PBLs to the target cells, and did not depend on
      the generation of soluble factors. CD3+, CD4-, CD8- and CD16- cells were found to
      be the major subset contributing to inhibition of the growth of RPMI 8226 cells,
      and this growth inhibition was cytostatic rather than cytotoxic. These
      characteristics distinguished it from growth inhibition mediated by the natural
      killer system. Impaired PBL-mediated growth inhibition of RPMI 8226 cells was
      found in patients with various hematologic diseases, including myeloma. It
      therefore appears that the CD3+, CD4-, CD8- and CD16- cell subset might be
      involved in tumor immunity in myeloma.

PMID- 1350159
TI  - Monocytes appearing repeatedly after chemotherapies had an identical
      rearrangement pattern of immunoglobulin with leukemic blasts in a patient with
      CD13+ acute lymphoblastic leukemia.
AB  - We recently encountered a patient with acute lymphoblastic leukemia (ALL) who
      showed temporal monocytosis of an unusually high cell count (5,000-30,000
      monocytoid cells/microliter) five times after treatment with different
      chemotherapies. The leukemic cells expressed B-cell-associated antigens, CD19 and
      CD10, E-rosette receptor, CD2 and monocyte/myeloid antigen, CD13 simultaneously.
      They were peroxidase-negative. One week after the initiation of conventional
      chemotherapy for ALL, the leukemic blasts had disappeared. Alternatively,
      monocytoid cells appeared along with the recovery from nadir status. They showed
      several features of monocytes; they were weakly dot-positive for nonspecific
      esterase, reactive with CD14 and CD13 and Fc gamma-receptor-positive.
      Furthermore, they migrated into a fungally infected joint space. Features
      incompatible with normal monocytes were the absence of peroxidase reactivity, the
      expression of B-cell-associated antigens, CD19 and CD10 and E-rosette receptor,
      CD2. Southern blot hybridization analysis revealed an unexpected result that
      HindIII digested DNA from both leukemic blasts and monocytoid cells had the same
      rearranged band of IgH. Thus, an identical clonality of monocytoid cells,
      temporally appearing after chemotherapies and leukemic lymphoblasts, was
      determined in this patient with CD13+ ALL.

PMID- 1350160
TI  - Successful treatment of chronic adult T-cell leukemia with ubenimex.
AB  - A 38-year-old Japanese man had suffered from trichophyton infection for several
      years. The white blood cell count was 20,300/mm3, including 54% abnormal
      lymphocytes with irregularly convoluted nuclei. Adult T-cell leukemia (ATL) was
      diagnosed based on proliferation of CD4-positive lymphocytes, positive anti-HTLV
      I antibody and monoclonal integration of proviral DNA. By 30 mg/day of ubenimex
      (Bestatin), the abnormal lymphocytes positive for CD4 in the peripheral blood
      were gradually reduced. Complete remission was maintained for 9 months without
      any antineoplastic agents. Ubenimex may have suppressed the growth of ATL cells
      in this patient. Accordingly, ubenimex may prove useful for treating some
      patients with chronic-type ATL.

PMID- 1350162
TI  - Proceedings from the meetings of the Scandinavian and Dutch national orthopedic
      societies, 1991. Abstracts.

PMID- 1350161
TI  - Secretion mode of the harderian gland of rats after stimulation by cholinergic
      secretagogues.
AB  - We studied the morphological changes in rat Harderian glands 30 min after
      injection of cholinergic secretagogues. In controls, the glands exhibited a
      tubuloalveolar structure with relatively wide lumina, in which some osmiophilic
      dense droplets exocytosed from glandular cells were observed. Also two types of
      glandular cells (type A cells and type B cells sometimes showing exocytotic
      figures of lipid-secretory vacuoles) and myoepithelial cells were recognized.
      After injection of carbamylcholine chloride (subcutaneously, 0.1 mg/kg body
      weight), which has both nicotinic and muscarinic actions, many of the alveolar
      lumina dilated and contained a small number of osmiophilic droplets. Exocytotic
      figures in both types of cells and a pronounced decrease in the number of
      vacuoles in the glandular cells were observed. However, there was no evidence of
      apocrine or holocrine secretion. The injection of the higher dose of
      carbamylcholine (1.0 mg/kg) caused fusion of secretory vacuoles in the apical
      cytoplasm and contraction of myoepithelial cells. Most alveoli showed no clear
      lumina; their centers were jammed with cytoplasmic fragments and accumulated
      secretory products. Massive discharge of cytoplasmic fragments containing some
      secretory vacuoles was often observed. This may be classified as apocrine
      secretion. Bethanechol chloride (subcutaneous injection, 1.0 mg/kg), a muscarinic
      agonist, stimulated the Harderian-gland secretion, and enhanced exocytosis was
      observed. The discharge from the glandular cells, following injection of various
      doses of carbamylcholine, were almost inhibited by atropine sulfate, a muscarinic
      antagonist. The present results suggested that the cholinergic systems regulate
      the secretion of rat Harderian-gland cells which have muscarinic receptors.

PMID- 1350164
TI  - Identification of spotted fever group rickettsiae using polymerase chain reaction
      and restriction-endonuclease length polymorphism analysis.
AB  - In order to facilitate the isolation and identification of spotted fever group
      (SFG) rickettsiae from their tick vectors, we used the centrifugation shell vial
      technique or traditional isolation procedures and genotypic identification using
      the restriction fragment length polymorphism analysis of polymerase chain
      amplified fragments. The presence of Rickettsia conorii both in Rhipicephalus
      sanguineus ticks collected in southern France, and in Rhipicephalus simus and
      Haemaphysalis leachi from Zimbabwe was demonstrated. This procedure seems to be
      of particular interest for studying the epidemiology and ecology of SFG
      rickettsiae.

PMID- 1350163
TI  - Alpha 2-receptor-mediated inhibition of intraluminal release of gastric
      somatostatin in anaesthetized rats.
AB  - The aim of the present study was to investigate how the sympathetic nervous
      system affects the vagally induced intragastric release of somatostatin and
      gastrin. Experiments were performed on anaesthetized rats in which the stomach
      was perfused with a dextrane solution (pH approximately 5.9) or dextrane buffer
      (pH 7.4). pH as well as gastrin and somatostatin levels were measured in the
      gastric perfusate when it had passed the stomach. Vagal stimulation caused a
      decrease in perfusate pH and an increase of the intraluminal output of gastrin
      and somatostatin when the stomach was perfused with the dextrane solution pH 5.9.
      Pretreatment with phentolamine (1 mg kg-1) significantly increased and
      pretreatment with clonidine (60 micrograms kg-1 h-1) significantly decreased
      somatostatin release caused by vagal stimulation, whereas gastrin levels remained
      largely unchanged. The effect of clonidine persisted in rats pretreated with
      indomethacin (5 mg kg-1), which per se potentiates the vagally induced luminal
      somatostatin release. When the stomach was perfused with the dextrane buffer pH
      7.4, basal gastrin levels were significantly higher than during perfusion with
      the solution pH 5.9, whereas somatostatin levels remained unchanged. Neither
      somatostatin nor gastrin levels increased following vagal stimulation during
      gastric perfusion with the dextrane buffer pH 7.4. However, following
      pretreatment with phentolamine somatostatin levels increased during these
      conditions.

PMID- 1350165
TI  - Persistence of Rickettsia prowazekii in cotton rat macrophage cultures.
AB  - Rickettsia prowazekii is able to multiply and persist for a long time in cotton
      rat macrophage culture (29-days observation period). Electron microscopic studies
      showed that the structure of Rickettsiae remained intact at different intervals
      post-inoculation (p.i.). In the course of persistence Rickettsiae revealed a
      reduced capacity to infect chick embryos and guinea pigs, however, the infectious
      agent could be isolated at all stages of persistence of cultured cells such as
      fibroblasts of the guinea pig embryo, macrophages of intact cotton rats.

PMID- 1350166
TI  - The effect of monocyte-derived macrophages on the growth of Rickettsia conorii in
      permissive cells.
AB  - We examined whether monocyte-derived macrophages (MdM) incubated with rickettsia
      infected HEp-2 or BGM cells a) affect R. conorii (Boutonneuse fever) growth, and
      b) secrete TNF and IL-1 alpha. BGM and HEp-2 cells were infected with R. conorii
      at multiplicities of infection (MOI) of 1-0.01. After 2 hr of adsorption, the
      cells were washed and MdM were added at an effector to target ratio of between 3
      and 5. At 2, 24, 48, and 96 hr post-infection (p.i.) cells were scraped off; cell
      free medium was collected and TNF and IL-1 levels were determined by ELISA and
      RIA, respectively. MdM caused a 50-70% reduction in the yield of R. conorii in
      HEp-2 cells as compared to the control (infected HEp-2 cells incubated without
      MdM). This reduction was more pronounced at MOI 0.1 and 0.01, than at MOI 1. In
      contrast, no reduction in the rickettsial yield was observed in the BGM cells
      incubated with MdM. TNF and IL-1 alpha levels in the cell-free medium from
      infected HEp-2 cells incubated with MdM were higher (2-5 fold) than those from
      infected BGM cells incubated with MdM. These data suggest the possibility that,
      and the mechanisms whereby, MdM may modulate rickettsia replication in vivo.

PMID- 1350167
TI  - Serum antibodies in rickettsia patients as determined by immunoblotting
      technique.
AB  - The Western-blot technique (WB) was used to determine which polypeptides of
      Israeli spotted fever (ISF) isolates and other spotted fever group rickettssia
      (SFGR) reference isolates (G212, S484, A828) and two reference strains. R.
      Rickettsii (Sheila Smith strain) and R. conorii (Boutonneuse fever), were used as
      antigen sources for the WB. Immunoperoxidase assay (IPA) seropositive (titer
      greater than 80) and seronegative (titer less than) sera were examined with the
      separated polypeptides of the above strains. WB analysis of the rickettsial
      polypeptide-serum reactions showed that R. conorii and the three isolates of ISF
      reacted identically with the sera, except that in the three ISF strains a 175 kD
      protein was present. It was also observed that all of the IPA seropositive sera
      examined reacted with the following polypeptides: 18kD, 20kD, 22kD (28kD to 37 kD
      LPS group), while each seropositive and seronegative serum reacted differently
      with polypeptides 23kD, 42kD, 45kD, 46kD, 52kD, 55kD, 70kD, 82kD, 105kD, 125kD,
      155kD and 175kD. Using this technique, no heat labile polypeptides
      (preelectrophoretic treatment: 100 degrees C for 2 min vs 37 degrees C for 20
      min) were observed in SFGR strains used in this study. Our results indicate that
      the immunoblot technique shows no difference between R. conorii and ISF antigens
      except the existence of 175kD protein antigen in the latter.

PMID- 1350168
TI  - Dynamics of non-specific antibacterial activity of the peritoneal cells of mice
      induced with Coxiella burnetii antigen.
AB  - It was found that primary immunization with Coxiella burnetii antigen increased
      mouse resistance to Salmonella typhimurium infection as evidenced by acceleration
      of bacterial elimination from the peritoneal cavity and a decrease in lethality
      of experimental animals. The existence of two rises of bactericidal activity of
      mouse peritoneal cells was ascertained: the "early" on days 1 and 2, and the
      "late" on day 14 after C. burnetii administration. The first rise was accompanied
      by some increase in the number of peritoneal cells as well as by some change of
      their qualitative representation. The second increase of antibacterial activity
      was detected during the pronounced cellular and humoral immune responses to C.
      burnetii.

PMID- 1350169
TI  - Ultrastructure of viable and inactivated Coxiella burnetii after inoculation of
      mice.
AB  - C3HA mice were inoculated intraperitoneally (i.p.) with viable Coxiella burnetii
      (C.b.) (strain Apodemus flavicollis-Luga, phase I) or C.b. antigen (formalin
      inactivated C.b.); pieces of spleen, liver, omentum, kidney, and suspension of
      peritoneal macrophages were examined by electron microscopy at 1, 7, 14, 21, 28,
      and 42 days post-infection (p.i.). Two main types of viable C.b. cells--small
      dense (DC) and bacteria-like (BC)--were found in omentum, spleen, and peritoneal
      exudate cells beginning from the 1st day p.i. but maximal amount they reached in
      spleen at day 14. Some parasitophorous vacuoles contained damaged BC or lysing
      C.b. cells. C.b. corpuscular antigen was found in phagosomes in ultrathin
      sections of spleen macrophages until 28 days p.i. By 7 days p.i. in omentum 3
      types of parasitophorous phagosomes were described which were supposed to be the
      sites of the antigen utilization. It is assumed that most BC are destroyed in
      omentum macrophages during the 1st week after i.p. injection of the antigen, and
      DC can persist in spleen at least for one month.

PMID- 1350171
TI  - Preliminary characterization of inflammatory infiltrates in response to
      Rickettsia prowazekii reinfection in man: immunohistology.
AB  - The local perivascular mononuclear cell inflammatory infiltrate (PVI) response to
      intradermal (ID) challenge with viable R. prowazekii was studied in a typhus
      immune subject. An immunohistochemical method for specific mononuclear cell
      markers was used on skin punch biopsies taken 6, 24 and 48 hr after challenge. By
      24 to 48 hr, the histologic findings were consistent with a delayed-type
      hypersensitivity reaction (DTHR). Both CD4+ and CD8+ T lymphocytes dominated the
      PVI at 48 h. CD8+ cells entered the PVI more rapidly than CD4+ cells. Local
      control of R. prowazekii challenge in an immune human subject was associated with
      recruitment into the PVI of T lymphocytes which are rich sources of gamma
      interferon, and CD8+ T cells which are potentially cytotoxic for R. typhi
      infected cells.

PMID- 1350170
TI  - Immunoblot analysis of antibody response in mice infected with Coxiella burnetii
      phase I.
AB  - Mouse sera collected from day 4 to day 133 postinfection (p.i.) with phase I
      Coxiella burnetii strain Nine Mile were analysed by immunoblotting with phase I
      C. burnetii cell lysate. Antibodies of IgG class protein antigens were revealed
      already on day 10 p.i. (60, 49 and 27 kD proteins), followed by those to 77 kD
      protein from day 18 p.i. and to further 7 (from 42 to 70 kD) proteins from day 28
      p.i. IgG antibody reaction was observed also with 5 antigens in 14-20 kD region
      corresponding to lipopolysaccharides from day 22 p.i. Surprisingly, antibodies of
      IgM type appeared later (from day 22 p.i.) and were directed only to protein
      antigens, most markedly to 60 and 77 kD proteins. Differences in immunoblot
      patterns observed with the serum collected on day 72 p.i. before and after
      absorption to phase I and phase II C. burnetii cells, and to phase I cells
      treated by trichloroacetic acid (TCA) or KIO4, indicate the surface localization
      of protein phase I antigenic epitopes, which can be destroyed partly by TCA and
      almost completely by KIO4 treatment.

PMID- 1350172
TI  - Protein antigens of genetically related Rickettsia prowazekii strains with
      different virulence.
AB  - The protein antigens of two distinct lines of genetically related strains, namely
      the nonpathogenic strain E and its virulent revertant EVir and of the standard
      virulent strain Breinl were compared in SDS-PAGE and immunoblot assay using
      typhus patient sera and immune rabbit sera. No differences in the polypeptide
      pattern as detected in SDS-PAGE were found between strain E and EVir; the Breinl
      strain differed in a 30 kD protein. The high immunogenicity of the protein
      antigens of E, EVir and Breinl strains was demonstrated by immunoblot assay with
      human sera, which did not show any differences between the strains studied.
      Immunoblot analysis with immune rabbit sera to the strain E, EVir, and Breinl
      showed differences in immunological response to the 70 kD and 60 kD polypeptides
      of low virulent strain E and those of virulent strains EVir and Breinl.

PMID- 1350173
TI  - Comparison of structural polypeptides, detected by immunoblotting technique, in
      the sera of spotted fever group rickettsia positive cases--symptomatic versus
      asymptomatic.
AB  - In an attempt to characterize the nature of symptomatic versus asymptomatic
      spotted fever group rickettsia (SFGR) infection, the immune response to R.
      conorii (boutonneuse fever) structural polypeptides was studied by Western-blot
      immunoassay. Sera from immunoperoxidase assay (IPA), SFGR seropositive (titre
      greater than or equal to 80) individuals, symptomatic and asymptomatic and from
      SFGR seronegative (IPA titre less than 80) individuals living in a kibbutz
      community in the desert region of Southern Israel were examined by immunoblot.
      This community suffered from a very high morbidity rate due to SFGR (21-fold
      higher than the national reported average). The entire community (n-326) has been
      followed-up since 1985, with serial serum samples being examined for specific IgG
      antibodies by IPA. The intensity of the immunoblot reaction correlated with
      specific IgG antibody titres as determined by IPA. This correlation was also
      observed between the decrease in the IgG titre and the strength of the antibody
      antigen reaction by immunoblot over time for a given individual. IPA seropositive
      sera from asymptomatic as well as symptomatic spotted fever cases reacted to 8
      individual polypeptides. In both cases antibodies to 22 kD, 24 kD, 26 kD, 28 kD,
      30 kD, 32 kD, 34 kD, and 37 kD were found. In the IPA seronegative sera,
      antibodies to polypeptides in the range of 24 kD to 32 kD were not detected. The
      lack of detectable differences by immunoblotting between SFGR symptomatic vs,
      asymptomatic cases might be explained by other aspects of the immune response of
      each infected individual, and/or it is possible that virulent and non-virulent
      antigenically closely related SFGR strains infected symptomatic vs. asymptomatic
      individuals.

PMID- 1350174
TI  - Kinetics of specific antibodies in Mediterranean spotted fever determined by
      western blotting and microimmunofluorescence.

PMID- 1350175
TI  - The reactivity between rickettsiae and Weil-Felix test antigens against sera of
      rickettsial disease patients.
AB  - Of the sera which were positive to Rickettsia tsutsugamushi by indirect
      immunoperoxidase test, approximately 80% sera were positive to a Proteus OXK
      antigen by Weil-Felix test at 10 or more days after the onset of fever, while
      only 10% sera were positive within 9 days from the onset of fever. In ELISA using
      the OXK antigen, almost all of the paired sera of tsutsugamushi disease (TD)
      patients increased on the IgM antibody titres with the rise of their titres by
      Weil-Felix test, whereas the IgG antibody titres of these sera were unrelated
      with the titres of Weil-Felix test. We suspect that the reactivity of TD patients
      sera to the OXK antigen in Weil-Felix test was derived from the reactivity of the
      IgM antibody against the OXK antigen common with R. tsutsugamushi. The patient
      sera infected with a Japanese isolate of spotted fever group rickettsia (SFGR)
      cross-reacted with the Thai Tick Typhus (TTT) strain of SFGR by indirect
      immunoperoxidase test. In Weil-Felix test, the reactivity of these sera to OX2
      antigen were higher than that to OX19 antigen, like the sera infected with other
      SFGR, except of R. rickettsii. These sera also reacted with TTT and OX2 antigens
      by ELISA. The titres of IgM antibody against OX2 antigen in the sera in ELISA
      were in parallel with the titres of the sera against OX2 antigen in Weil-Felix
      test, but not the titres of IgG antibody. We suggest that the reactivity of the
      patient sera infected with SFGR to OX2 antigen of Weil-Felix test is dependent on
      the IgM antibody.

PMID- 1350176
TI  - Phenotypic and genotypic heterogeneity of 8 new human Coxiella burnetti isolates.
AB  - Eight new strains of Coxiella burnetii were isolated from chronic Q fever
      patients using centrifugationashell vial technique. Seven patients had
      endocarditis (including one patient with an immunodeficiency syndrome), and one
      had a vascular prosthesis infection. Three prototype strains, Nine Mile phase II,
      Q212 and Priscilla and eight new isolates were cultured in L 929 cells.
      Heterogeneity of their cytopathic effect was observed. DNAs of the eleven strains
      have been isolated and purified by standard procedures. Plasmid DNA was separated
      from chromosomal DNA by a low melting point gel. Electrophoresis in agarose gel
      showed that seven of the eight new strains had plasmids which were about 40 kb
      (plasmid V517 was used as size marker). Endonuclease-restriction analysis of the
      8 human isolates is currently under investigation.

PMID- 1350177
TI  - Immunoblot analysis of IgG subclass antibody response against Coxiella burnetii
      in Balb/c mice.
AB  - Balb/c mice were inoculated with live or inactivated organisms of Coxiella
      burnetii, strain Nine Mile, phase I. Sera collected after different time
      intervals were subjected to immunoblot analysis and results compared with ELISA
      values. Immunoblots were performed with different horseradish peroxidase labelled
      conjugates (goat anti-mouse IgG1, IgG2a, IgG2b, IgG3) and results monitored and
      analysed by laser densitometry. ELISA analysis was performed using the same
      peroxidase labelled goat anti-mouse subclass antibody conjugates. In addition,
      goat anti-mouse IgG(H+L), IgG(H), IgM, and IgA conjugates were used for ELISA
      tests.

PMID- 1350178
TI  - Influence of Coxiella burnetii infection of male mice on their offspring.
AB  - The dramatic spread of Q fever in Poland among cattle kept in isolation from
      natural environment (ticks, wild animals) has suggested the possibility that the
      infection may also be transmitted sexually. To test this hypothesis series of
      experiments have been performed in controlled laboratory conditions. Male mice
      infected with C. burnetii were allowed to mate with healthy female mice. On day
      18 of pregnancy serum IgM antibodies to C. burnetii antigens and bacteria in
      spleen, liver and placenta were detected. The influence of C. burnetii
      transmission between parents of their offspring was investigated. It has been
      found that C. burnetii infection in males diminish the number of fertilized
      females. Their litters are fewer in number and the number of dead embryos is
      increased.

PMID- 1350179
TI  - DNA probes for detecting Coxiella burnetii strains.
AB  - Methods have been developed for the rapid detection of C. burnetii by specific
      hybridization of labelled DNA probes to rickettsial plasmid DNA sequences present
      in clinical samples. One DNA probe detects all C. burnetii strains, while
      additional probes differentiate, between organisms associated with chronic or
      acute disease. Using these probes, C. burnetii can be identified in blood, urine,
      and tissue samples. The plasmid-derived DNA probes detect as few as 10(4)
      organisms and less than 1 ng of Coxiella DNA. Host-cell DNA has no effect on the
      hybridization signal from C. burnetii DNA, and these probes do not cross-react
      with a variety of microorganisms, including both common laboratory contaminants
      and organisms that cause clinical symptoms similar to those of Q fever. The
      sensitivity of the assay is markedly enhanced when the procedure employs the
      polymerase chain reaction (PCR) to amplify C. burnetii DNA. This requires
      construction of oligonucleotide primers to DNA sequences flanking the target
      region of the DNA being amplified. For C. burnetii detection, several sets of
      primers have been prepared. One set is derived from the QpH1 H fragment, a region
      that is shared by all C. burnetii plasmids (homologous sequences are also present
      in the plasmidless strains of C. burnetii). The H primers detect all strains of
      C. burnetii. To differentiate between C. burnetii strains, additional primers,
      specific for DNA sequences that are unique either to chronic or acute disease
      related strains of C. burnetii are employed. PCR amplifies target sequences up to
      10(6)-fold. When DNA hybridization is used in conjunction with PCR, the test can
      detect less than 10 C. burnetii cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350180
TI  - Cloning and expression in Escherichia coli of the 37-, 14-, and/or 16-kilodalton
      antigens genes from Rickettsia prowazekii strain E.
AB  - A gene bank of Rickettsia prowazekii strain E constructed in the phage vector
      lambda EMBL4 was screened for antigen production with anti-R. prowazekii serum.
      One of the immunoreactive clones, grown at 37 degrees C exhibited the expression
      of at least two antigens of molecular weight (M(r)) 37 kD and 14 kD. Subcloning
      and further analysis revealed that the antigens (polypeptides) of Mr 37, 14,
      and/or 16 kD apparently represent structural units of the 138 kD complex antigen.
      Assembly of the above mentioned polypeptides was found to be thermosensitive as
      it took place at 30 degrees C but not at 37 degrees C and resulted in an
      oligomeric structure of M(r) 138 kD. The nucleotide sequence of the gene coding
      for a precursor of the mature polypeptides of Mr 14 and/or 16 kD was determined.

PMID- 1350182
TI  - Inhaled beta agonists.

PMID- 1350181
TI  - Neuroleptic medication and prescription practices with sheltered-care residents:
      a 12-year perspective.
AB  - OBJECTIVES: Most adult residents of sheltered-care facilities (board and care,
      family care, psychosocial rehabilitation, and other supported housing
      arrangements) for the chronically mentally ill receive neuroleptics. These
      facilities house over 300,000 mentally ill residents, but neuroleptic
      prescription practices with this population have not been studied. METHODS: A
      probability sample (n = 393) of all adult former psychiatric patients in
      sheltered care in California was surveyed in 1973; 94% of the located survivors
      (n = 243) were reinterviewed 12 years later. RESULTS: In 1973, 79% received
      neuroleptics; in 1985, 76%. Polypharmacy decreased, and the elderly remained less
      medicated than adults. Yet, mean daily neuroleptic doses doubled, more persons
      received higher doses, and 62% reported adverse effects. Furthermore, high dosing
      was attributed to psychiatrists rather than other physicians, even when
      controlling for residents clinical and sociodemographic characteristics.
      CONCLUSIONS: Neuroleptic drugs became the staple pharmacological treatment for
      mentally ill sheltered-care residents. While physicians more cautiously medicated
      the elderly, they had not reduced doses by 1985, even after a decade of
      treatment. The specialty of the prescriber was an important factor in preference
      for high-dose treatment.

PMID- 1350183
TI  - Inhaled beta agonists.

PMID- 1350184
TI  - Serotype, hemolysin production, and adherence characteristics of strains of
      Escherichia coli causing urinary tract infection in dogs.
AB  - Virulence factors were studied in 82 strains of Escherichia coli isolated from
      the urine of dogs with urinary tract infections. The most frequently expressed O
      antigens were 2, 4, 6, 25, and 22/83. Most strains were K nontypeable. Mannose
      sensitive hemagglutination (MSH) with canine erythrocytes was observed in 71
      strains and mannose-resistant hemagglutination (MRH) was observed in 32 strains.
      Strains that caused MSH of erythrocytes from dogs also caused MSH of erythrocytes
      from guinea pigs. Most strains that caused MRH of human A1P1 erythrocytes also
      reacted with erythrocytes of dogs. Of 22 strains (27%) that agglutinated human
      A1P1 erythrocytes, but not A1p erythrocytes, 17 (77%) had specificity for globo
      A, but did not react with the galactose alpha 1----4galactose beta disaccharide
      receptor. The remaining 5 strains and 2 others that simultaneously expressed an X
      adhesin agglutinated galactose alpha 1----4galactose beta-coated latex beads.
      Bacterial adherence to canine uroepithelial cells from the bladder was most often
      observed in strains expressing MSH, less often observed in strains expressing
      MRH, and least often observed in strains that failed to induce hemagglutination.
      Adherence of MSH strains to canine uroepithelial cells was inhibited by alpha
      methyl-D-mannoside. As a group, MRH strains expressing globo-A- and galactose
      alpha 1----4galactose beta-specific adhesins did not have strong adherence.
      Strains of E coli isolated from dogs with urinary tract infections most commonly
      expressed type-1 fimbriae, and the main mechanism of in vitro adherence to canine
      uroepithelial cells involved a mannose-sensitive mechanism. Overrepresentation of
      globo-A-specific adhesins did not appear to be related to adherence of canine
      uroepithelial cells.

PMID- 1350185
TI  - Efficacy of AHR-13268, an antiallergenic compound, in the management of pruritus
      caused by atopic disease in dogs.
AB  - Twenty-nine pruritic, atopic dogs were entered into a double-blind, placebo
      controlled, crossover study to evaluate the efficacy of an investigational
      antiallergenic compound, AHR-13268. Fourteen dogs were evaluated by a veterinary
      dermatologist (at intervals) and the owner (daily). Fifteen dogs were evaluated
      only by the owner. The mean (+/- SE) owner scores for pruritus, erythema, and
      lesions with placebo treatment (higher score = worse signs) were 3.24 (+/- 0.12),
      2.73 (+/- 0.12), and 2.61 (+/- 0.09), respectively. With drug treatment, the
      corresponding scores were 2.89 (+/- 0.12), 2.50 (+/- 0.12), and 2.25 (+/- 0.09).
      Scores for pruritus and lesions (but not erythema) were significantly better with
      drug treatment than with placebo treatment. Investigator scores showed similar
      trends, but the differences were not great enough to be statistically
      significant. Overall, 11/29 (38%) owners reported their dogs had moderate or
      better improvement from drug capsules, and 4/29 dogs (14%) improved on placebo
      capsules. A variety of adverse effects were reported following both drug (9/29
      dogs) and placebo (8/29 dogs) capsule administration, but were mild and well
      tolerated. Results of this study indicate that AHR-13268 has potential for
      empiric treatment of allergic inhalant dermatitis in some dogs.

PMID- 1350186
TI  - Residency reform: a perspective from the Association of Professors of Medicine.

PMID- 1350187
TI  - Tinkering or real reform? The choice is ours.

PMID- 1350189
TI  - Kinship profiles and their errors.

PMID- 1350188
TI  - Apparent heterozygote deficiencies observed in DNA typing data and their
      implications in forensic applications.
AB  - Restriction fragment length polymorphisms (RFLP) analysis using the Southern blot
      technique can be used to recognize copy number variation of variable number of
      tandem repeats (VNTR) of conserved core sequences at several regions of the human
      genome. This new class of polymorphisms reveals a high degree of genetic
      variation, useful for individual identification purposes. Criticisms against
      forensic applications of such DNA typing data include the limitation of employing
      Hardy-Weinberg expectation of genotype frequencies, since several surveys
      indicate apparent deficiency of heterozygosity (or excess homozygosity) in
      comparison with Hardy-Weinberg expectations. This research postulates an
      alternative explanation of deficiency of apparent heterozygosity which is caused
      by the inability to detect extremely small-sized alleles (called 'non-detectable'
      alleles) due to the sensitivity of Southern gel electrophoresis. We show that the
      presence of 'non-detectable' alleles can produce pseudo-homozygosity and their
      frequencies can be predicted from the observed proportional heterozygote
      deficiency. Furthermore, in the covert presence of such 'non-detectable' alleles,
      we show that the gene-count method provides over-estimates of allele frequencies
      in the sample population, and hence the Hardy-Weinberg predictions of genotype
      frequencies avoid wrongful bias against suspects in forensic applications of DNA
      typing data. Applications of this theory to population data on six VNTR loci in
      US Caucasians and US Blacks suggest that the presence of 'non-detectable' alleles
      could be the major cause of apparent heterozygote deficiency, and the current
      approaches of predicting the population frequency of specific DNA phenotypes are
      practically free of the possible wrongful bias in courtroom applications of DNA
      typing data.

PMID- 1350190
TI  - Chronic neuroleptic treatment: D2 dopamine receptor supersensitivity and striatal
      glutamatergic transmission.
AB  - We studied the in vitro electrical activity of rat neostriatal neurons following
      chronic neuroleptic treatment. In haloperidol-treated rats, unlike naive animals,
      activation of neostriatal D2 dopamine receptors induced a potent presynaptic
      inhibition of glutamate-mediated excitatory synaptic potentials. Haloperidol
      treatment did not affect the intrinsic membrane properties of the neostriatal
      neurons. Pre- and postsynaptic physiological responses to direct and indirect
      gamma-aminobutyric acid (GABA)-ergic and cholinergic agonists were not affected
      by chronic haloperidol treatment. These findings suggest that movement disorders
      induced by chronic neuroleptic treatment may result, at least in part, from a
      hypersensitivity of presynaptic D2 dopamine receptors regulating the release of
      glutamate.

PMID- 1350191
TI  - ANNA 23rd National Symposium. Chicago, April 30-May 3, 1992. Abstracts.

PMID- 1350193
TI  - Dipeptidyl peptidase II- and IV-like activities in gingival tissue and crevicular
      fluid from human periodontitis lesions.
AB  - Gingival tissue and gingival crevicular fluid were collected from patients with
      chronic periodontitis. Gel filtration chromatography of crude tissue extracts
      yielded separate fractions active against Lys-Ala-7-amino-4-trifluoromethyl
      coumarylamide (AFC) at acid pH and Gly-Pro-AFC at alkaline pH. The molecular
      weights, pH optima and inhibitor responses of these activities were consistent
      with those of dipeptidyl peptidases (DPP) II and IV, respectively. When tested
      with the same substrates, crevicular fluid was also found to contain DPP II- and
      IV-like activities with very similar pH profiles and inhibitor responses to those
      in tissue. The close resemblance suggested that the crevicular fluid enzymes were
      derived mainly from inflamed gingival tissues. Slight differences in the DPP II
      like activities might be explained by the additional presence in crevicular fluid
      of enzymes from subgingival bacteria. With use of appropriate buffers, a third
      substrate, Ala-Pro-AFC, gave selective detection of both DPP II- and IV-like
      activities in tissue and crevicular fluid. Assays with Ala-Pro-AFC had the
      advantage of greater sensitivity, especially with DPP II-like activity. Raised
      levels of this enzyme have previously been found in the gingiva of periodontitis
      patients and thus DPP II-like activity in crevicular fluid might prove of value
      in monitoring disease activity.

PMID- 1350192
TI  - Prospective trial comparing the use of sulphasalazine and auranofin as second
      line drugs in patients with rheumatoid arthritis.
AB  - Two hundred patients with rheumatoid arthritis were studied in a prospective open
      trial comparing treatment with sulphasalazine and auranofin in patients with
      active disease over 12 months. The two drugs improved many parameters of disease
      activity at 12, 24, and 48 weeks. At 12 weeks, the group treated with
      sulphasalazine had a lower platelet count (Mann-Whitney U test), erythrocyte
      sedimentation rate, and articular index, with a greater decrease in erythrocyte
      sedimentation rate (Students t test) and C reactive protein between 0 and 12
      weeks. There were no significant differences between sulphasalazine and auranofin
      treatment after 24 and 48 weeks. Life table analysis showed no significant
      differences in the rate of side effects which caused treatment to be stopped.
      Sulphasalazine works more rapidly, may be a more effective disease modifying
      antirheumatic drug, and is as well tolerated as auranofin.

PMID- 1350194
TI  - Inflammatory bowel disease presenting in pregnancy.
AB  - A case of inflammatory bowel disease (IBD) presenting in pregnancy is described.
      Despite previous reports of severe fulminating disease in this type of patient,
      this woman did well with an uncomplicated course; she responded to standard
      medical therapy and there were no fetal complications. IBD should not be a
      contraindication to pregnancy unless the disease is poorly controlled. Pregnancy
      does not increase the risk of relapse of IBD, but should this occur it is more
      likely in the first trimester or in the postpartum period. Treatment of IBD in
      pregnancy should be much the same as in the nonpregnant woman. Corticosteroids
      and sulphasalazine are safe in pregnancy and are the mainstays of medical
      treatment. Surgery should proceed for the usual indications of toxic megacolon
      and perforation. In the group requiring surgery fetal mortality is considerable
      but the maternal outcome is improving. Patients presenting with IBD in pregnancy
      may have more severe disease but recent reports suggest that the outcome for
      mother and infant in this group is improving.

PMID- 1350195
TI  - The homeodomain: a new face for the helix-turn-helix?
AB  - The discovery of conserved protein domains found in many Drosophila and mammalian
      developmental gene products suggests that fundamental developmental processes are
      conserved throughout evolution. Our understanding of development has been
      enhanced by the discovery of the widespread role of the homeodomain (HD). The
      action of HD-containing proteins as transcriptional regulators is mediated
      through a helix-turn-helix motif which confers sequence specific DNA binding.
      Unexpectedly, the well conserved structural homology between the HD and the
      prokaryotic helix-turn-helix proteins contrasts with their divergent types of
      physical interaction with DNA. A C-terminal extension of the HD recognition helix
      has assumed the role that the N-terminus of the prokaryotic helix plays for
      specification of DNA binding preference. However, the HD appears also capable of
      recognizing DNA in an alternative way and its specificity in vivo may be modified
      by regions outside the helix-turn-helix motif. We propose that this intrinsic
      complexity of the HD, as well as its frequent association with other DNA binding
      domains, explains the functional specificity achieved by genes encoding highly
      related HDs.

PMID- 1350196
TI  - Neuropeptides and classical transmitters. Localization and interaction.
AB  - The present article briefly reviews some aspects on the localization and possible
      functional roles of neuropeptides. It is emphasized that a large number of
      peptides can be found in the nervous system and that they in many instances occur
      together with classical transmitters such as acetylcholine and catecholamines in
      the same neurons. In agreement, functional studies have revealed that they
      interact in different ways, both synergistically and antagonistically, with the
      transmitters. In some instances peptides may also have trophic effects. The
      recent cloning of neuronal peptide receptors has further substantiated a
      physiological role for these compounds in the nervous system. Moreover, the
      recent development of peptide antagonists, which pass the blood brain barrier,
      now opens up new possibilities to elucidate the functional role of neuropeptides
      and thus of the coexistence phenomenon.

PMID- 1350197
TI  - Glutamatergic-dopaminergic balance in the brain. Its importance in motor
      disorders and schizophrenia.
AB  - Dopamine appears to be of less importance in the regulation of psychomotor
      functions than was previously thought. A central dopaminergic-glutamatergic
      balance may be important for both akinetic motor disorders and psychosis. In
      Parkinson's disease glutamate antagonists may counteract central glutamatergic
      hyperactivity and may be of value as anti-parkinsonian drugs. An increase of
      dopaminergic activity and/or a reduction of glutamatergic activity may contribute
      to the development of paranoid hallucinatory psychosis in schizophrenic patients
      and of pharmacotoxic psychosis in Parkinson's disease. Because of possibly severe
      side-effects of glutamatergic antagonists and agonists in the treatment of
      akinesia and psychosis, the development of partial glutamate agonists/antagonists
      could be an alternative strategy capable of producing antipsychotic or anti
      kinetic effects with only mild adverse reaction.

PMID- 1350198
TI  - Overexpression of the c-erbB-2/neu-encoded p185 protein in primary lung cancer.
AB  - The c-erbB-2/neu gene encodes a transmembrane protein of 185 kDa (p185) with
      tyrosine kinase activity and extensive sequence homology to epidermal growth
      factor receptor. Amplification and overexpression of the c-erbB-2/neu gene has
      been shown in certain human tumors and is postulated to be important in human
      carcinogenesis. High levels of expression of the c-erbB-2/neu gene have been
      reported in non-small-cell lung cancer (NSCLC) cell lines and primary tumors from
      the United States. Since geographical and cultural factors may contribute to the
      development of certain types of cancer, we examined p185 examined p185 expression
      in 120 tumors from Chinese patients with lung cancers of different cell types and
      used immunohistochemical staining to determine the extent and general
      significance of p185 expression in human primary lung cancer. Our results
      demonstrate that 58.8% of the NSCLCs expressed p185 and that expression of p185
      was observed only in NSCLC and not in small-cell lung cancers. Thirty-three of 41
      adenocarcinomas and 24 of 55 squamous cell carcinomas among the NSCLCs examined
      were found to express p185 at levels different from those of normal lung. For the
      squamous cell carcinomas, p185 expression was correlated with lymph node
      metastasis (P less than 0.01), but for the adenocarcinomas, it was not (P greater
      than 0.05). In addition, expression of p185 in NSCLC was significantly more
      frequent in patients in advanced clinical stages. Our findings indicate that p185
      expression is a frequent event and a general phenomenon in NSCLC and is
      correlated with poor clinical prognostic indicators, suggesting that expression
      of p185 may be of potential prognostic importance in NSCLC.

PMID- 1350199
TI  - Inhibition of human, ovine, and baboon neutrophil elastase with Eglin c and
      secretory leukocyte proteinase inhibitor.
AB  - The association rate constants (kon) of human, ovine, and baboon neutrophil
      elastase with two recombinant serine proteinase inhibitors (Eglin c, secretory
      leukocyte proteinase inhibitor) were compared. The association rate constant of
      sheep leukocyte elastase (SLE) with Eglin c is about 100 times lower (kon = 2.2 x
      10(5) M-1s-1) than that of human elastase (kon = 2.4 x 10(7) M-1s-1). Baboon
      elastase, however, is as effectively blocked with Eglin c (kon = 2.5 x 10(7) M-1s
      1) as human elastase. Secretory leukocyte proteinase inhibitor (SLPI) blocks the
      elastase of all three species with high efficiency; baboon elastase shows the
      highest association rate constant (kon = 5.6 x 10(7) M-1s-1) followed by human
      elastase (kon = 4.1 x 10(7) M-1s-1) and finally sheep elastase (kon = 1.2 x 10(7)
      M-1s-1). These findings demonstrate marked differences in the inhibition kinetic
      properties of ovine and human elastase. Concerning a future clinical application
      of proteinase inhibitors, the baboon seems a more suitable model than sheep to
      evaluate the effects of Eglin c and SLPI, since both inhibitors block baboon and
      human elastase with comparable efficiency.

PMID- 1350200
TI  - Long-term cholinergic denervation caused by early postnatal AF64A lesion prevents
      development of muscarinic receptors in rat hippocampus.
AB  - The effect of early postnatal (day 8) intracerebroventricular injections of the
      putative cholinotoxin ethylcholine aziridinium mustard (AF64A) on development of
      cholinergic innervation and postsynaptic muscarinic acetylcholine receptors in
      the rat hippocampus was examined. The cholinotoxin applied at this stage of
      development leads to a permanent denervation of cholinergic fibres in the
      hippocampus in adulthood demonstrated by (immuno)histochemical methods and
      biochemical assays. Muscarinic receptor expression in the principal neurons of
      dentate gyrus and cornu ammonis was strongly reduced as studied by immunostaining
      with antibodies against muscarinic receptor proteins and binding assays with the
      muscarinic antagonist quinuclidinyl benzilate. Cholinoceptive interneurons and
      somatostatinergic interneurons are not affected by the developmental cholinergic
      lesion. Immunoreactivity to protein kinase C type I as a marker for
      inositolphosphate-related cellular activation systems slightly decreased in the
      apical dendrites of the hippocampal principal neurons. These findings indicate
      that damage to ingrowing cholinergic terminals in the hippocampus in the early
      postnatal period is a critical hazard for development of the muscarinic receptor
      system in the hippocampal principal neurons. These results are discussed for
      their significance to the neural mechanisms that underlie perinatal brain damage
      and associated cognitive dysfunction.

PMID- 1350201
TI  - Molecular cloning and expression of a high affinity L-proline transporter
      expressed in putative glutamatergic pathways of rat brain.
AB  - We have used the polymerase chain reaction (PCR) with degenerate oligonucleotides
      derived from two conserved regions of the norepinephrine and gamma-aminobutyric
      acid transporters to identify novel Na(+)-dependent transporters in rat brain.
      One PCR product hybridized to a 4.0 kb RNA concentrated in subpopulations of
      putative glutamatergic neurons including mitral cells of the olfactory bulb,
      pyramidal cells of layer V of the cerebral cortex, pyramidal cells of the
      piriform cortex, and pyramidal cells of field CA3 of the hippocampus. Transient
      expression of the cognate cDNA conferred Na(+)-dependent L-proline uptake in HeLa
      cells that was saturable (Km = 9.7 microM) and exhibited a pharmacological
      profile similar to that for high affinity L-proline transport in rat brain
      slices. The cloned transporter cDNA predicts a 637 aa protein with 12 putative
      transmembrane domains and exhibits 44%-45% amino acid sequence identity with
      other members of the emerging family of neurotransmitter transporters. These
      findings support a synaptic role for L-proline in specific excitatory pathways in
      the CNS.

PMID- 1350202
TI  - Telencephalon-restricted expression of BF-1, a new member of the HNF-3/fork head
      gene family, in the developing rat brain.
AB  - We have previously characterized a novel transcription factor family in mammals,
      the HNF-3 family, by the members' homology to one another and to the Drosophila
      homeotic gene fork head. The expression of fork head is restricted to the
      anterior and posterior termini of the early fly embryo. Brain factor 1 (BF-1) is
      a new member of this family isolated from rat brain with an expression pattern
      and DNA binding specificity distinct from the HNF-3 genes. Expression is highly
      restricted in the developing neural tube to its rostral end, which gives rise to
      the telencephalon. These results suggest that BF-1 plays an important role in the
      establishment of the regional subdivision of the developing brain and in the
      development of the telencephalon.

PMID- 1350203
TI  - Oxygen or glucose deprivation-induced neuronal injury in cortical cell cultures
      is reduced by tetanus toxin.
AB  - We examined glutamate-mediated neurotoxicity in cortical cell cultures pretreated
      with 1-5 micrograms/ml tetanus toxin to attenuate the Ca(2+)-dependent release of
      neurotransmitters. Efficacy of the tetanus toxin pretreatment was suggested by
      blockade of electrical burst activity induced by Mg2+ removal and by reduction of
      glutamate efflux induced by high K+. Tetanus toxin reduced neuronal injury
      produced by brief exposure to elevated extracellular K+ or to glutamate,
      situations in which release of endogenous excitatory neurotransmitter is likely
      to play a role. Furthermore, although glutamate efflux evoked by anoxic
      conditions may occur largely via Ca(2+)-independent transport, tetanus toxin
      attenuated both glutamate efflux and neuronal injury following combined oxygen
      and glucose deprivation. With prolonged exposure periods, the neuroprotective
      efficacy of tetanus toxin was comparable to that of NMDA receptor antagonists.
      Presynaptic inhibition of Ca(2+)-dependent glutamate release may be a valuable
      approach to attenuating hypoxic-ischemic brain injury.

PMID- 1350204
TI  - Light stimulation of the hypothalamic neuroendocrine system.
AB  - This paper demonstrates that, in the mediation of light, the suprachiasmatic
      nucleus (SCN) functionally associates with the anterior periventricular and
      parvocellular paraventricular neuron systems in rats. Intact rats (group 1) and
      rats undergoing a hemicomplete cutting of the SCN (group 2) were housed in a dark
      room (2-3 weeks) and killed after an exposure to light for 10, 30 or 60 min.
      Other intact animals (group 3) kept in a dark room (2 weeks) were exposed to
      light for 10 min, then stored 60 min in the dark room, and killed in darkness.
      The SCN, anterior periventricular nucleus, and parvocellular paraventricular
      nucleus were examined immunohistochemically using antisera for vasoactive
      intestinal polypeptide (VIP), arginine vasopressin, somatostatin, rat
      corticotropin releasing factor (rCRF), and c-fos protein. In comparison with
      animals kept in darkness, animals exposed for 10 and 30 min to light indicated a
      remarkable reduction of VIP immunoreactivity in the SCN and some increase of CRF
      immunoreactivity in the parvocellular paraventricular nucleus. The diminution of
      VIP immunoreactivity did not occur in the isolated SCN of group 2 animals. In
      group 3, a 10 min-light exposure induced a remarkable enhancement of nuclear c
      fos immunoreactivity in neurons in the ventrolateral region of the SCN, in the
      anterior periventricular nucleus, and in the parvocellular paraventricular
      nucleus, most strongly in the SCN. Double immunolabeling methods have shown that
      VIP, somatostatin, and CRF neurons in the respective nuclei were c-fos positive.

PMID- 1350205
TI  - Enantioselective pharmacokinetics of ethotoin in humans following single oral
      doses of the racemate.
AB  - Racemic ethotoin (1000 mg) was administered orally as a single dose to six
      healthy adult volunteers. Blood samples were collected at appropriate times for
      120 h following the dose. Ethotoin was quantified enantio-selectively in plasma
      using a novel chiral column HPLC procedure. One of the enantiomers of the chiral
      metabolite, 5-phenylhydantoin, was also quantified in the HPLC method. The Cmax
      and AUC0-infinity values for (+)-(S)-ethotoin were significantly greater than
      those for (-)-(R)-ethotoin (ratio of mean AUC0-infinity values 0.88), but the
      elimination half-lives of the isomers were virtually identical [12.35 +/- 5.15 h
      for (-)-(R)-ethotoin; 12.28 +/- 5.34 h for (+)-(S)-ethotoin]. Parameters derived
      from AUC0-infinity (Cl0/F and V(area)/F) also differed slightly between the
      isomers. The data were interpreted as indicating a small difference in the
      absorption of the two isomers; it seemed unlikely, in terms of the identical
      elimination rates, that their metabolic profiles would differ greatly. The 5
      phenylhydantoin was eliminated with a significantly longer half-life (18.69 +/-
      6.11 h) than that of ethotoin. Enantioselectivity in the pharmacokinetics of
      ethotoin is therefore a minor issue.

PMID- 1350206
TI  - Chromatographic resolution of the chiral isomers of several beta-blockers over
      cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase.
AB  - The optical resolution of seven beta-blockers which have in common the N
      isopropyl-3-aryloxy-2-hydroxypropylamine moiety was carried out by HPLC using the
      cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase to
      quantitatively characterize the enantioselectivity of these compounds. The
      capacity factors and separation factors at different column temperature were
      determined with some qualitative trends derived. A compensation effect was
      observed for these compounds where there exists an approximately linear
      relationship between the enantiomeric differences in enthalpic and entropic
      energies.

PMID- 1350208
TI  - Follow-up of retinoblastoma patients having prenatal and perinatal predictions
      for mutant gene carrier status using intragenic polymorphic probes from the RB1
      gene.
AB  - We have carried out presymptomatic prediction of mutant gene carrier status in
      ten individuals with a family history of retinoblastoma. In all cases standard
      linkage studies were employed using intragenic DNA probes which recognise
      restriction fragment length polymorphisms. In four cases foetal DNA samples were
      obtained by chorionic villus sampling, the remaining six were derived from either
      cord blood samples or venipuncture of neonates. We demonstrated that the mutant
      gene was inherited by only one of these patients who has subsequently developed
      bilateral tumours. Six of the other cases have now reached the age beyond which
      it might have been expected that tumours would develop and are all disease free.
      It must be concluded that repeated ophthalmological examination of these and
      future patients shown not to have inherited the mutant gene, is unnecessary.

PMID- 1350209
TI  - Retinogeniculate EPSPs recorded intracellularly in the ferret lateral geniculate
      nucleus in vitro: role of NMDA receptors.
AB  - We used an in vitro preparation of the ferret lateral geniculate nucleus (LGN) to
      examine the role of the NMDA class of excitatory amino acid (EAA) receptors in
      retinogeniculate transmission. Intracellular recordings revealed that blockade of
      NMDA receptors both shortened the time course and reduced the amplitude of fast
      and slow components of excitatory postsynaptic potentials (EPSPs) evoked by optic
      tract stimulation. The amplitude and width of the EPSPs mediated by NMDA
      receptors increased as membrane potential was depolarized towards spike
      threshold. Individual LGN cells were influenced to varying extents by blockade of
      NMDA receptors; NMDA and non-NMDA receptor blockade together attenuated severely
      the entire retinogeniculate EPSP. The dependence of all components of
      retinogeniculate EPSPs (and action potentials) on NMDA receptor activation
      supports the hypothesis that the NMDA receptor participates in fast (less than 10
      ms) synaptic events underlying conventional retinogeniculate transmission. The
      voltage dependence of the NMDA receptor-gated conductance suggests strongly that
      the transmission of retinal information through the LGN is subject to modulation
      by extraretinal inputs that affect the membrane potential of LGN neurons.

PMID- 1350207
TI  - Different types of non-P-glycoprotein mediated multiple drug resistance in
      children with relapsed acute lymphoblastic leukaemia.
AB  - Although cellular drug resistance is considered to be an important cause of the
      poor prognosis of children with relapsed acute lymphoblastic leukaemia (ALL), the
      knowledge of drug resistance in these patients is very limited. Different aspects
      of drug resistance were studied in 17 children with relapsed ALL. The in vitro
      sensitivity profile was determined using the MTT assay. Cells from relapsed
      children were significantly more resistant to 6-thioguanine, prednisolone,
      cytosine arabinoside, daunorubicin (DNR), mustine-HCl and mafosfamide but not to
      L-asparaginase and vincristine (VCR) than cells from 41 children with ALL at
      initial diagnosis. Some relapsed patients showed a general drug resistance while
      others were resistant to only 1-3 drugs. The relevance of the multidrug
      resistance (MDR) model was analysed: In all DNR- and VCR resistant cases a co
      resistance to drugs not involved in the MDR model was found. P-glycoprotein was
      not detected in any of 28 untreated and 14 relapsed samples tested. VCR- and DNR
      accumulation in the most resistant cells were not lower than in sensitive cells.
      Resistance modifiers did not potentiate the cytotoxicity of VCR and DNR. We
      conclude that resistance to anthracyclines and vinca alkaloids in childhood
      relapsed ALL is not due to P-glycoprotein mediated MDR. Different types of drug
      resistance varying from a resistance to only one drug to a general
      chemoresistance, can be detected in children with relapsed ALL. VCR and L
      asparaginase seemed to be only infrequently involved in drug resistance.
      Knowledge of drug resistance might lead to more effective and less toxic
      therapies for children with relapsed ALL.

PMID- 1350210
TI  - Lower respiratory tract infections after abdominal operations: epidemiology and
      risk factors.
AB  - OBJECTIVE: To find out the incidence and aetiology of lower respiratory tract
      infections after abdominal operations and identify predisposing factors. DESIGN:
      Prospective open study. SETTING: Department of General Surgery, Hospital Germans
      Trias i Pujol, Barcelona, Spain. SUBJECTS: 2,083 patients having abdominal
      operations between March 1985 and June 1987 excluding splenectomies, and those
      requiring thoracoabdominal incisions. MAIN OUTCOME MEASURES: The presence of
      three or more of the following: temperature of 38 degrees C or more, cough with
      mucopurulent sputum, raised white cell count, or changes on the chest radiograph
      or bronchogram. RESULTS: 50 patients (2.4%) developed lower respiratory tract
      infections. Micro-organisms were isolated from 15 (30%), the most common being
      Haemophilus influenzae. The most important risk factors were American Society of
      Anesthesiologist's grade, duration of anaesthesia, age, and operations on the
      upper gastrointestinal tract. CONCLUSION: Further work is needed to investigate
      other possible predisposing factors and develop a predictive score.

PMID- 1350211
TI  - Wound infection after cholecystectomy. Correlation between bacteria in bile and
      wound infection after operation on the gallbladder for acute and chronic
      gallstone disease.
AB  - OBJECTIVE: To see if there was a difference in the wound infection rates after
      operation for acute and chronic cholecystitis, and to see if the presence of
      bacteria in the bile had any influence on those rates. DESIGN: Prospective open
      study. SETTING: University hospital. SUBJECTS: 213 Patients undergoing
      cholecystectomy for acute or chronic gallstone disease. MAIN OUTCOME MEASURES:
      Incidence of postoperative wound infection, and of bile cultures growing
      pathogenic organism. RESULTS: There was no difference in wound infection rates
      between patients operated on for acute and those operated on for chronic
      cholecystitis. The presence of bacteria in the bile did not seem to influence the
      wound infection rate in either group. CONCLUSIONS: Early cholecystectomy and
      appropriate antibiotic prophylaxis result in an acceptably low wound infection
      rate, and the growth of bacteria from bile is not predictive of the development
      of wound infection.

PMID- 1350212
TI  - Advantages and disadvantages of using the hydrogen clearance technique to measure
      pancreatic blood flow.
AB  - This study was undertaken to identify the advantages and disadvantages of using
      the hydrogen clearance technique (HCT) to measure pancreatic blood flow (PBF) in
      the opossum over short and long periods. An open study was performed on 8
      opossums. A total of 72 platinum electrodes were implanted into the pancreas. On
      the fifth day 41 additional electrodes were implanted. All implantation sites
      were examined histologically after five days. Measurements of pancreatic blood
      flow were taken every other day for five days. Three measurements were taken from
      each electrode and the mean of the three was used for analysis. In the
      anaesthetized animal mean PBF (SD) was 63.5 (12.8) ml min-1 100 g-1 immediately
      after electrode implantation and 34.3 (11.4) ml min-1 100 g-1 on the 5th
      postoperative day. Of the implanted electrodes, 35% failed during the
      experimental course, mainly as the result of proliferation of scar tissue around
      the electrodes. Mild to moderate fibroproliferation had taken place around the
      platinum tips of the remaining 65%. Primary electrode implantation caused no or
      negligible trauma to the pancreas. We recommend the HCT only for short-term
      measurements of PBF. Implantation of electrodes for any length of time leads to
      inflammatory changes around the platinum tips that cause proliferation of scar
      tissue and lead to failure of the electrodes, misleadingly low PBF recordings,
      and fewer monoexponential clearance curves.

PMID- 1350213
TI  - Pancreatico-duodenectomy: 13-years' experience.
AB  - This paper reports a retrospective study of 51 consecutive pancreatico
      duodenectomies from a Swedish university hospital concerning postoperative
      morbidity, number of reoperations and mortality. Resection of the distal common
      bile duct, duodenum, and head of the pancreas with hemigastrectomy and
      cholecystectomy was done in 48 patients and modified pancreaticoduodenectomy with
      preservation of the pylorus was done in three patients. Three patients (6%) died
      within 30 days. Nine patients required reoperation, three more than once. The
      most common major complications were anastomotic breakdown (n = 7), severe
      hemorrhage (n = 3) and abscess formation (n = 3). We conclude that a low
      postoperative morbidity and mortality can be achieved outside large, specialist
      centres, but the operation should be done by experienced surgeons. The results
      may justify carrying out the operation when the chances of cure are small, but it
      has yet to be evaluated as a palliative procedure.

PMID- 1350214
TI  - Acute mesenteric ischaemia.
AB  - To identify any differences in presentation among the four types of acute
      mesenteric ischaemia, and to correlate time between presentation and treatment
      with outcome, we retrospectively analysed 100 cases of acute mesenteric ischaemia
      at a University hospital diagnosed by radiography (n = 21), at laparotomy (n =
      61), or at necropsy (n = 18). A total of 68 patients died. Mortality was 50% when
      the aetiology was embolic occlusion of the superior mesenteric artery and 95%
      when the occlusion was thrombotic; 67% when the disease was "non"-occlusive; and
      30% in cases of splanchnic vein thrombosis. We conclude that early diagnosis is
      critical for successful management of acute mesenteric ischaemia, but outcome is
      also influenced by the aetiology.

PMID- 1350215
TI  - Giant appendix with diffuse ganglioneuromatosis. An unusual presentation of von
      Recklinghausen's disease.

PMID- 1350216
TI  - Spontaneous rupture of the spleen.
AB  - A 40-year-old woman with bronchial asthma was admitted as a medical emergency
      with suspected myocardial infarction. Spontaneous splenic rupture was diagnosed
      during hospitalization and splenectomy successfully performed. No histopathologic
      changes or signs of previous injury or adhesions were found.

PMID- 1350217
TI  - Subcutaneous avulsion of the breast caused by a seat belt injury. Report on a
      case requiring emergency mastectomy.
AB  - A 60-year-old female car driver wearing a combined three-point lap-shoulder seat
      belt was involved in a head-on-collision. The entire right breast was separated
      from the chest wall, whereas the overlying skin remained intact. The injury
      resulted in a rapid development of a monstrous haematoma in the retromammary
      space, and required emergency mastectomy. Seat belt lesions of the female breast
      are seldom referred in the literature.

PMID- 1350218
TI  - Review of clinical trials of low molecular weight heparins.

PMID- 1350219
TI  - Importance of dehydration in anastomotic and subcutaneous wound healing: an
      experimental study in rats.
AB  - OBJECTIVE: To find out if preoperative and postoperative dehydration adversely
      affect anastomotic and subcutaneous healing. DESIGN: Randomized study. MATERIAL:
      18 Wistar rats. INTERVENTIONS: Dehydration established in nine rats by withdrawal
      of food and water for 24 hours before operation, and by injections of frusemide
      twice daily. Laparotomy and division of intestine 5-8 cm from the ileocaecal
      valve. Implantation of expanded polytetrafluoroethylene (ePTFE) tubes in the
      backs of the necks. All rats killed after five days. MAIN OUTCOME MEASURES:
      Measurements of weight loss and of hydroxyproline per centimetre in the ePTFE
      tubes and standardized biopsy specimens of the intestine. Presence of anastomotic
      dehiscence at necropsy. RESULTS: Preoperative and postoperative dehydration
      caused a 24% weight loss in the experimental group on day 5 compared with 8% in
      the control group. Dehydrated animals accumulated less collagen in the ePTFE
      tubes than control animals (p less than 0.05). There were three anastomotic
      breakdowns in the dehydrated group compared with one in the control group. There
      was a loose but significant correlation between collagen accumulation in the
      anastomoses and the weight of the animal (r = 0.5, p less than 0.05). CONCLUSION:
      Preoperative and postoperative dehydration has a deleterious effect on
      subcutaneous, and to a lesser extent on anastomotic healing in rats.

PMID- 1350220
TI  - Efficacy of recombinant erythropoietin for stimulating erythropoiesis after blood
      loss and surgery. An experimental study in rats.
AB  - Perioperative administration of recombinant human erythropoietin (rEpo) may
      reduce the need for allogeneic blood transfusions by diminishing the time lag
      between blood loss and erythropoiesis and by generating more adequate Epo levels.
      The efficacy of pre- and postoperative rEpo was studied in rats subjected to
      blood loss (20% of the blood volume) and surgery (ileal resection). After 200 U
      rEpo/kg daily for 5 days postoperatively, hemoglobin had increased by 15.7 g/l in
      these rats but by 36.9 g/l in rEpo-treated controls without surgery (p less than
      0.05), indicating an inhibitory effect of surgery on erythropoiesis. A course of
      200 U rEpo/kg/day for 5 days, starting 4 or 2 days before operation and blood
      loss, resulted in significantly higher postoperative hemoglobin levels than in
      untreated controls. Such difference did not occur if rEpo treatment was begun on
      the day of operation. Prolonged (10-day) postoperative rEpo treatment was of
      minor benefit, inducing significant increase in hemoglobin and hematocrit only
      from day 8 onwards. The study indicates that rEpo is a promising agent to obviate
      need for perioperative blood transfusions, provided that the treatment is begun
      before operation.

PMID- 1350221
TI  - Septic shock in rats treated with terbutaline alone and in combination with
      chemotherapeutics, dexamethasone, and infusion of 3% albumin.
AB  - The effects of a beta 2-receptor agonist, terbutaline, on haematocrit and
      survival were studied in rats in which septic shock had been induced by
      intraperitoneal injection of a mean (SD) dose of 6.0 (4.5) x 10(8) live E. coli.
      Untreated septic animals developed haemoconcentration, the mean (SD) haematocrit
      increasing from 47.5 (1.4) to 53.1 (2.2). Mean (SD) survival time was 8.9 (0.6)
      hours, and no animal survived for 24 hours. Terbutaline given as the only
      treatment in doses of 0.1, 0.5, and 2.5 mg/kg before injection of E. coli
      significantly reduced the haemoconcentration, with haematocrit of 51.9, 46.6 and
      47.9, respectively, at 4 hours. Survival was not significantly prolonged. When
      terbutaline was started 5.5 hours after injection of E. coli and given in
      addition to a chemotherapeutic drug (trimethoprim + sulphamethoxazole) and
      dexamethasone, haematocrit were reduced, 24 hour survival improved from 44% to
      68%, and 7 day survival improved from 20% to 48%. We conclude that terbutaline
      given alone counteracts the loss of plasma volume during septicaemia and, when
      combined with a chemotherapeutic and dexamethasone, significantly improves long
      term survival.

PMID- 1350222
TI  - On the value of giving a combination of drugs for the treatment of endotoxaemia
      in pigs.
AB  - OBJECTIVE: To see if treatment with a combination of drugs each directed at a
      different mediator was successful in preventing activation of those mediators in
      experimental endotoxic shock. DESIGN: Controlled study. MATERIAL: 40 juvenile
      pigs. INTERVENTIONS: 33 animals received 0.01 mg/kg endotoxin infusion, the rest
      being given the same volume of saline; 10 of the 33 received no treatment. Of the
      remaining 23, 5 were given combination treatment with methylprednisolone,
      naloxone, ketanserin, promethazine, C1 esterase inhibitor, antithrombin III and
      aprotinin; 7 were given methylprednisolone only; 6 were given the three protease
      inhibitors (C1 esterase inhibitor, antithrombin III and aprotinin); and 5 were
      given naloxone, ketanserin and promethazine. MAIN OUTCOME MEASURES: Assessment of
      haemodynamic, proteolytic, and cellular effects of endotoxaemia. RESULTS: Only
      the combination treatment totally blocked all the effects of the infusion of
      endotoxin. CONCLUSION: As endotoxin affects several mediators, combination
      treatment is necessary to block all its deleterious effects in pigs.

PMID- 1350223
TI  - 4th International TNF Congress. The Netherlands, May 2-6, 1992. Abstracts.

PMID- 1350224
TI  - Characterization of thymic cell subpopulations involved in IL-1- or GM-CSF
      induced IL-6 production.
AB  - IL-6 has been demonstrated by in vitro studies to be a cytokine involved in
      thymocyte activation We show herein that thymocytes cultured at high
      concentrations in the absence of comitogen respond to IL-1 and, to a lesser
      degree, to GM-CSF, by producing IL-6. This phenomenon disappears rapidly with
      decreasing cell densities, suggesting the involvement of a minor cellular
      component of the thymus which may be solely responsible for or cooperate in IL-6
      production. We have analysed several thymic subpopulations for IL-6 production
      and show that accessory cells, and eventually their precursors, are the major if
      not exclusive, producers of this cytokine. Mature steroid-resistant thymocytes do
      not secrete IL-6. Production of IL-6 by total CD4-CD8- thymic cells is largely
      reduced by the depletion of mature accessory cells which express I-A and Mac-1
      antigens. As shown previously, accessory cell precursors within the CD4-CD8-
      compartment are induced to differentiate into M phi and DC in response to IL-1
      and GM-CSF. We provide evidence that this maturation is associated with IL-6
      production. Thymic DC and phagocytic cells of the thymic reticulum (P-TR) in
      vitro produce high levels of IL-6 which are enhanced by GM-CSF or IL-1. These
      factors have a synergistic effect on IL-6 production by total thymocytes, and on
      CD4-CD8- cells that are not depleted for mature I-A+ Mac-1+ accessory
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350225
TI  - Cloning and analysis of the CD18 promoter.
AB  - CD18, the common beta chain of the leukocyte integrin adhesion proteins, is
      expressed exclusively by myeloid cells and lymphocytes. During myeloid
      differentiation, the increase in CD18 cell surface expression is paralleled by
      increased CD18 messenger RNA levels. Nuclear run-on studies show that CD18
      expression is transcriptionally regulated during 12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced HL-60 monocytic differentiation. The CD18 transcriptional
      start site was defined by primer extension and RNAse protection. The gene
      encoding CD18 was cloned and a fragment that overlaps the transcriptional start
      site was isolated. DNA sequence analysis of this promoter fragment identified
      potential AP-1 elements that may mediate the TPA transcriptional response. The
      CD18 promoter also contains a putative binding site for PU.1, a leukocyte
      specific transcription factor. DNA elements resembling those found in other
      myeloid and integrin promoters were identified. The CD18 promoter fragment was
      linked to the luciferase reporter gene, electroporated into the U937 monocytic
      cell line, and its expression increased after exposure to TPA. Thus, CD18 may
      serve as a model for identifying the cis elements and trans-acting factors that
      regulate gene expression during myeloid differentiation.

PMID- 1350226
TI  - Prognostic value of proliferating cell nuclear antigen expression in chronic
      lymphoid leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is a usually indolent disease that can assume
      an aggressive clinical course in some patients. To develop assays that would be
      predictive of how a particular patient's disease would evolve, we studied the
      expression of proliferating cell nuclear antigen (PCNA) by Western blotting in 40
      patients with CLL. The concentration of PCNA, a cofactor for delta DNA-dependent
      DNA polymerase, is indicative of the proliferative state of the cell.
      Significantly lower PCNA levels were observed in earlier stage CLL when compared
      with more advanced disease. The leukemic cell proliferative rate, assessed by
      lymphocyte doubling time and flow cytometry, also correlated significantly with
      the level of PCNA expression. These results suggest that a high level of PCNA in
      the cells of CLL patients at presentation identifies a subgroup of patients whose
      CLL cells have a higher proliferative activity and who may, therefore, have a
      potentially shorter survival.

PMID- 1350227
TI  - Human erythrocyte protein 4.2: isoform expression, differential splicing, and
      chromosomal assignment.
AB  - Human protein 4.2 (P4.2) is a major membrane skeletal protein in erythrocytes.
      Individuals with P4.2 deficiency exhibit spherocytosis and experience various
      degrees of hemolytic anemia, suggesting a role for this protein in maintaining
      stability and integrity of the membrane. Molecular cloning of P4.2 cDNAs showed
      that P4.2 is a transglutaminaselike molecule in erythrocytes but lacks the
      essential cysteine for cross-linking activity. Two cDNA isoforms have been
      identified from a human reticulocyte cDNA library, with the long isoform
      containing a 90-base pair (bp) in-frame insertion encoding an extra 30 amino
      acids near the N-terminus. Characterization of the P4.2 gene suggests
      differential splicing as the mechanism for generating these two cDNA isoforms.
      The donor site for the short isoform (P4.2S) agrees better with the consensus
      than the donor site for the long isoform (P4.2L) does. Expression of P4.2L was
      detected by a long-isoform-specific antibody raised against a peptide within the
      30-amino acid insert. Western blot analyses showed P4.2L to be a minor membrane
      skeletal protein in human erythrocytes with an apparent molecular weight (mol wt)
      of approximately 3 Kd larger than the major protein 4.2, P4.2S. By in situ
      hybridization of a full-length 2.4-kilobase (kb) cDNA to human metaphase
      chromosomes, the gene for P4.2 was mapped to bands q15-q21 of chromosome 15, and
      it is not linked to the gene for coagulation factor XIIIa (plasma
      transglutaminase, TGase).

PMID- 1350228
TI  - Double-intensive therapy in high-risk multiple myeloma.
AB  - A high remission rate is achieved with high-dose melphalan (HDM) in multiple
      myeloma (MM), and autologous transplantation of hematopoietic stem cells allows a
      prompt hematologic recovery after high-dose therapy. We treated 97 patients with
      high-risk MM (group 1:44 advanced MM including 14 primary resistances and 30
      relapses; group 2: 53 newly diagnosed MM) with a first course of HDM. For
      responding patients a second course of high-dose therapy with hematopoietic stem
      cell support was proposed. After the first HDM, the overall response and complete
      remission rates were 71% and 25% with no significant difference between the two
      groups. The median durations of neutropenia and thrombocytopenia were
      significantly longer in group 1 (29.5 days and 32 days, respectively) than in
      group 2 (23 days and 17 days, respectively). This severe myelosuppression led to
      eight toxic deaths and the fact that only 38 of the 69 responders could proceed
      to the second course (three allogenic and 35 autologous transplantations). Among
      the 35 patients undergoing autologous transplantation (10 in group 1, 25 in group
      2), 31 received their marrow unpurged collected after the first HDM, and four
      received peripheral blood stem cells. The median durations of neutropenia and
      thrombocytopenia after autologous transplantation were 24 days and 49 days,
      respectively. Two toxic deaths and nine prolonged thrombocytopenias were
      observed. The median survival for the 97 patients was 24 months (17 months in
      group 1, 37 months in group 2) and the median duration of response was 20 months.
      The only parameters that have a significant impact on the survival are the age
      (+/- 50 years) and the response to HDM. The median survival of the 35 patients
      undergoing autologous transplantation is 41 months, but the median duration of
      remission is 28 months with no plateau of the remission duration curve. Patients
      responding to HDM may have prolonged survival, but even a second course of high
      dose therapy probably cannot eradicate the malignant clone.

PMID- 1350229
TI  - Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte
      macrophage colony-stimulating factor for hematologic support after high-dose
      intensification for breast cancer.
AB  - High-dose therapy with autologous marrow support results in durable complete
      remissions in selected patients with relapsed lymphoma and leukemia who cannot be
      cured with conventional dose therapy. However, substantial morbidity and
      mortality result from the 3- to 6-week period of marrow aplasia until the
      reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth
      factors, particularly used after chemotherapy, can increase the number of
      peripheral blood progenitor cells (PBPCs) present in systemic circulation. The
      reinfusion of PBPCs with marrow has recently been reported to reduce the time to
      recovery of adequate marrow function. This study was designed to determine
      whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs
      alone (without marrow) would result in rapid and reliable hematopoietic
      reconstitution. Sixteen patients with metastatic breast cancer were treated with
      four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction).
      Patients responding after the first two cycles were administered GM-CSF after the
      third and fourth cycles to recruit PBPCs for collection by two leukapheresis per
      cycle. These PBPCs were reinfused as the sole source of hematopoietic support
      after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or
      hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes
      greater than or equal to 500/microL was observed on a median of day 14 (range, 8
      to 57). Transfusion independence of platelets greater than or equal to
      20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three
      patients required the use of a reserve marrow for slow platelet engraftment. In
      retrospect, these patients were characterized by poor baseline bone marrow
      cellularity and poor platelet recovery after AFM induction therapy. When compared
      with 29 historical control patients who had received the same high-dose
      intensification chemotherapy using autologous marrow support, time to
      engraftment, antibiotic days, transfusion requirements, and lengths of hospital
      stay were all significantly improved for the patients receiving PBPCs. Thus,
      autologous PBPCs can be efficiently collected during mobilization by chemotherapy
      and GM-CSF and are an attractive alternative to marrow for hematopoietic support
      after high-dose therapy. The enhanced speed of recovery may reduce the morbidity,
      mortality, and cost of high-dose treatment. Furthermore, PBPC support may enhance
      the effectiveness of high-dose therapy by facilitating multiple courses of
      therapy.

PMID- 1350230
TI  - Ex vivo incubation with growth factors enhances the engraftment of fetal
      hematopoietic cells transplanted in sheep fetuses.
AB  - Hematopoietic stem cells (HSC) transplanted in utero are in competition with
      endogenous HSC; thus, ultimately the graft constitutes a relatively small
      fraction of total HSC pool. To enhance the engraftment of donor cells in sheep
      fetuses, we preincubated these cells, ex vivo, for 16 hours at 37 degrees C with
      the conditioned medium from phytohemagglutinin-stimulated lymphocytes (PHA-LCM)
      before in utero transplantation. PHA-LCM is a rich source of hematopoietic growth
      factors in sheep. Subsequent engraftment was significantly higher in cells
      preincubated with PHA-LCM compared with fresh cells or those incubated with
      control medium only. This was reflected in all markers of the donor cells
      (hemoglobin type, karyotype, and progenitor cell assays). Brief ex vivo
      incubation with PHA-LCM also increased viability of all marrow cells as well as
      total numbers of progenitors. Similar enhancement of engraftment was also noted
      in monkeys after a brief preincubation of donor cells with interleukin-3 (IL-3)
      and granulocyte-macrophage colony-stimulating factor (GM-CSF). We conclude that
      brief (16 hours) ex vivo incubation of donor cells with a source of such growth
      factors as IL-3 and GM-CSF enhances the subsequent engraftment of transplanted
      cells.

PMID- 1350231
TI  - Elderly patients with sustained hypertension.

PMID- 1350232
TI  - Effect of azelastine on the seasonal increase in non-specific bronchial
      responsiveness to methacholine in pollen allergic patients. A randomized, double
      blind placebo-controlled, crossover study.
AB  - Azelastine, a phthalazinone derivative, is a new potent, long acting, orally
      active anti-allergic compound with particularly strong H1-histamine receptor
      antagonistic effects which has been proven to possess in vitro and in vivo a
      number of anti-inflammatory properties. The aim of the present study was to
      investigate whether azelastine would be able to prevent and/or reverse the
      seasonal increase in non-specific bronchial responsiveness to methacholine in
      pollen allergic patients. Twelve atopic patients (5 males, mean age 31 years),
      skin positive exclusively to grass and/or Parietaria pollen extract, with
      rhinitis and mild asthma occurring in the spring for at least two years
      previously, were studied. After a 2 week run-in period, oral azelastine, 4 mg
      twice daily, or placebo, was given for 2 weeks from the start of the pollen
      season, according to a randomized, double-blind design. After 2 weeks, the
      treatments were crossed over. During both the run-in and study periods, patients
      recorded rhinitis and asthma symptoms, additional antihistamine and
      bronchodilator drugs taken and peak expiratory flow measurements. A methacholine
      inhalation test was carried out on four occasions in each patient: before the run
      in period, before the start of the treatment, and at the end of the two 2 week
      treatment periods. Azelastine significantly reduced rhinitis symptoms and the
      need for antihistamine drugs, whereas asthmatic symptoms, use of bronchodilator
      drugs, peak flow recordings and bronchial responsiveness to methacholine were
      unaffected by the treatment. Compliance level and adverse side-effects were not
      significantly different between active treatment and placebo. In the final
      subjective evaluation of the two treatments, eight out of 12 patients preferred
      azelastine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350234
TI  - Modification of DENA-induced hepatocarcinogenesis by CCl4 cirrhosis. Comparison
      of the marker enzyme patterns.
AB  - The modifying action of chronic liver injury on the process of
      hepatocarcinogenesis was investigated. To induce cirrhosis or fibrosis F344 rats
      received CCl4 alone or in combination with phenobarbital, either before (model 1)
      or after (model 2) the application of initiator, diethylnitrosamine (DENA). In
      these models, morphology, tumor incidence as well as polysubstrate monooxygenase
      system, gamma-glutamyltransferase (GGT) and glucose-6-phosphatase (G-6-Pase) were
      studied. The data presented show that in model 1 the tumor incidence was much
      lower than in rats treated with DENA alone. This reduction appeared to be
      associated with the decrease in cytochrome P450 content occurring in model 1
      after DENA administration. Promotion of the hepatocarcinogenic process was
      observed when CCl4 injury followed the application of DENA (model 2). Comparison
      of marker enzymes in cirrhotic livers and in tumors either with or without
      cirrhosis indicated that changes in cytochrome P450 and G-6-Pase were rather the
      results of parenchymal damage, while GGT was elevated only in tumorous livers. In
      tumorous livers none of the xenobiotic metabolizing activities decreased as much
      as the cytochrome P450 content of the same samples. Thus conceivably the
      cytochrome P450 operates more rapidly in tumors than in normal livers.

PMID- 1350233
TI  - Pharmacology of antiarthritic drugs.
AB  - The clinical use of corticosteroids and second-line antirheumatic drugs provides
      relief in many patients but is associated with short-term and long-term toxicity.
      The beneficial effects are evident but are not well understood, particularly for
      the second-line agents. Rheumatoid arthritis is associated with abnormalities in
      macrophage, lymphocyte, and fibroblast functions. Corticosteroids and second-line
      agents appear to alter many of these responses (Table 2). Effects on macrophage
      and other antigen processing and phagocytic cells are common, but T- and B
      lymphocytes also may be affected. Some of these agents have direct anti
      inflammatory properties by inhibiting prostaglandin or leukotriene synthesis. A
      few are able to inhibit fibroblast proliferation and secretion of inflammatory
      mediators. Many other activities are possible. Understanding pharmacokinetics
      also should assist in determining dosing, possible consequences of other
      disorders, and predicting duration of acute effects. A better understanding of
      the disease process in rheumatoid arthritis and other disorders treated with
      these agents will lead to the better therapeutic approaches and, it is hoped, the
      discovery of more specific and less toxic agents.

PMID- 1350235
TI  - The hemodynamic effects of adrenergic blocking agents.
AB  - The various antihypertensive agents reduce blood pressure by different
      mechanisms. Alpha-1 receptor blockers reduce vascular resistance and maintain
      cardiac output. Chronic treatment with beta blockers without intrinsic
      sympathomimetic activity produces a fall in blood pressure which is associated
      with a fall in cardiac index and heart rate. Beta blockers with strong intrinsic
      sympathomimetic activity showed reduced heart rate during exercise. Labetalol
      reduces cardiac output and peripheral vascular resistance with little or no
      reduction in peripheral blood flow. Alpha-1 blockers are suitable for patients
      with active life-styles, with peripheral vascular disorders, or with high blood
      cholesterol levels. Beta blockers are useful in patients who have tachycardia,
      palpitation problems, or angina pectoris, or who have survived a heart attack.
      They should not be used in patients with bronchial asthma, reduced peripheral
      blood flow, or heart failure. Labetalol reduces blood pressure in a somewhat
      larger fraction of patients than the pure alpha- or beta-blocking agents. It is
      hoped that its long-term results will include regression of cardiovascular
      damage, improved quality of life, and increased life expectancy.

PMID- 1350236
TI  - Tl-201 chloride scan in multiple endocrine neoplasia type 2A.

PMID- 1350238
TI  - Electrical Impendance Tomography. 4th European Community workshop. York, 24-27
      July 1991.

PMID- 1350237
TI  - Neuroendocrine and side effect profile of pramipexole, a new dopamine receptor
      agonist, in humans.
AB  - The effects and tolerability of pramipexole, a new dopamine D2-receptor agonist,
      on prolactin, human growth hormone, thyrotropin, cortisol, and corticotropin
      levels were investigated in a randomized, double-blind, crossover study in 12
      healthy volunteers. Single oral doses of 0.1, 0.2, and 0.3 mg pramipexole and
      placebo were studied over a period of 24 hours. Pramipexole decreased serum
      prolactin levels in a dose-dependent manner, with a maximum effect after 2 to 4
      hours. Serum levels of human growth hormone were dose-dependently increased;
      however, this effect was only significant 2 hours after drug administration.
      Furthermore, a slight increase in serum cortisol levels and a slight decrease in
      serum thyrotropin levels was observed. Our findings show for the first time
      pharmacodynamic effects of pramipexole after single oral doses in healthy
      volunteers. The compound was well tolerated and showed an endocrine profile
      similar to other dopamine D2-agonists.

PMID- 1350239
TI  - [The mechanism of action of benzodiazepine and its consequences for therapy].
AB  - Kinetics and mechanism of action of benzodiazepines are at the base of their
      proper use in clinical management of anxiety, tension, panics, and insomnia.
      These important agents have specific receptors within the complex GABA-ergic
      system: according to the most recent studies, GABAA receptors are more important
      than GABAB receptors. The author illustrates the management of anxiety states, as
      well as the treatment of anxiety in children, in old people and of panic attacks.
      Since the use of benzodiazepines has become excessive, the risk of dependence is
      discussed as well as possible alternatives (buspirone, antidepressants). Finally,
      the usefulness of anxiolytic drug treatment is stressed which is one of the
      pivots of psychopharmacology and the study of the GABA-ergic system.

PMID- 1350240
TI  - The structure, role, and regulation of type 1 protein phosphatases.
AB  - Type 1 protein phosphatases (PP-1) comprise a group of widely distributed enzymes
      that specifically dephosphorylate serine and threonine residues of certain
      phosphoproteins. They all contain an isoform of the same catalytic subunit, which
      has an extremely conserved primary structure. One of the properties of PP-1 that
      allows one to distinguish them from other serine/threonine protein phosphatases
      is their sensitivity to inhibition by two proteins, termed inhibitor 1 and
      inhibitor 2, or modulator. The latter protein can also form a 1:1 complex with
      the catalytic subunit that slowly inactivates upon incubation. This complex is
      reactivated in vitro by incubation with MgATP and protein kinase FA/GSK-3. In the
      cell the type 1 catalytic subunit is associated with noncatalytic subunits that
      determine the activity, the substrate specificity, and the subcellular location
      of the phosphatase. PP-1 plays an essential role in glycogen metabolism, calcium
      transport, muscle contraction, intracellular transport, protein synthesis, and
      cell division. The activity of PP-1 is regulated by hormones like insulin,
      glucagon, alpha- and beta-adrenergic agonists, glucocorticoids, and thyroid
      hormones.

PMID- 1350242
TI  - Modern Trends in Orthopaedic Surgery and Pathology. 1st International Meeting.
      Bologna, April 11-13, 1991.

PMID- 1350241
TI  - Retinal microvessels express less gamma-glutamyl transpeptidase than brain
      microvessels.
AB  - In this investigation we localized and compared the level of gamma-glutamyl
      transpeptidase (GGTP) activity in retinal and brain preparations using
      histochemical, enzymatic and in situ hybridization assays. We compared GGTP
      distribution to another microvessel specific enzyme, alkaline phosphatase (AP).
      In the rat brain, GGTP activity was observed in microvessels and choroid plexus
      by a histochemical method. Similar studies in the rat retina revealed activity in
      the pigment epithelium but only a very weak reaction in microvessels.
      Histochemical staining for alkaline phosphatase was observed in both retinal and
      brain microvessels choroid plexus and pigment epithelium. Biochemical analysis
      verified that GGTP activity was significantly lower in retinal than brain
      microvessels, while alkaline phosphatase activity was similar in both types of
      microvessels. GGTP specific activity of bovine brain and retinal microvessels was
      185 +/- 39 mUnits and 8.5 +/- 1.5 mUnits (p less than 0.001), respectively. By
      contrast, alkaline phosphatase specific activity in brain and retinal
      microvessels was 732 +/- 139 and 471 +/- 114 (p greater than 0.1), respectively.
      Choroid plexus and retinal pigment epithelium exhibited similar levels of GGTP
      and alkaline phosphatase. Differences in GGTP expression between retinal and
      brain microvessels were also observed on the mRNA level. In situ hybridization
      studies revealed that brain microvessels expressed four times more GGTP specific
      mRNA than retinal microvessels. We conclude that retinal microvessels do not
      express high levels of GGTP which may make them more vulnerable than brain
      microvessels to injuries mediated by leukotrienes and oxidative stress.

PMID- 1350244
TI  - Abstracts of the 2nd International Symposium on Brain-Gut Interactions.
      Cambridge, United Kingdom, July 7-10, 1992.

PMID- 1350245
TI  - Laser lithotripsy of pancreatic and biliary stones via 3.4 mm and 3.7 mm
      miniscopes: first clinical results.
AB  - The pulsed dye laser is safe and effective in lithotripsy of biliary and
      pancreatic ductal stones, however delivery of the laser energy to the site of the
      calculi is technically difficult. A 3.4 mm miniscope inserted through a standard
      duodenoscope was used for transpapillary laser application under direct vision in
      one patient with an impacted pancreatic stone and in three patients with bile
      duct stones not amenable to treatment by routine endoscopy. Lithotripsy and
      ductal clearance was achieved in 3 of the 4 patients within a single treatment
      session. Percutaneous transhepatic laser lithotripsy via a 3.7 mm miniscope
      succeeded in the patient in whom the peroral approach had failed and in two
      further patients with bile duct stones not accessible by a retrograde approach.
      There were no major complications. The miniscopes provide an appropriate direct
      visual control for laser lithotripsy of pancreatobiliary calculi. This approach
      using miniscopes seems to be an effective, minimally invasive and time-saving
      alternative to conventional endoscopic laser lithotripsy.

PMID- 1350243
TI  - Sulfasalazine. Multiplicity of action.

PMID- 1350247
TI  - Parma.

PMID- 1350246
TI  - An anti-peptide antibody that recognizes the dopamine D2 receptor from bovine
      striatum.
AB  - The bovine dopamine D2 receptor was purified by wheat-germ-agglutinin-Sepharose
      chromatography and affinity chromatography, using the D2-receptor-specific
      agonist N-0434. Purification yields a preparation with a major protein band of 95
      kDa. In order to ascertain the identity of this protein, polyclonal antibodies
      against the dopamine D2 receptor have been raised using synthetic peptides based
      on the predicted amino acid sequence of the cloned D2 receptor. For the initial
      screening of these antibodies, three fusion proteins consisting of beta
      galactosidase and receptor fragments were constructed. One antiserum reacted
      strongly with the corresponding D2 receptor fusion protein, both on Western blots
      and in immunoprecipitation experiments. In each case, recognition was inhibited
      by competition with free peptide. On Western blots of partially purified receptor
      preparations from bovine striatum, the antiserum specifically recognized a 95-kDa
      glycoprotein. From similar preparations, the antiserum precipitated a substantial
      proportion of active D2 receptor, as determined by a decrease in [3H]spiperone
      binding in the supernatant. Active receptor could be released from the
      immunoprecipitate by addition of free peptide. Immunocytochemical analysis of
      cells transiently transfected with DNA coding for the D2 receptor showed specific
      staining of transfected cells. The antibody raised against a sequence in the
      third intracellular loop is able to shift the affinity of the receptor for
      dopamine from high to low, indicating that the antiserum may be interfering with
      receptor-GTP-binding-protein interactions.

PMID- 1350248
TI  - Synergistic effect of IL-3 and IL-6 on highly enriched murine hemopoietic
      progenitors.
AB  - It has been reported that interleukin 6 (IL-6) acts on hemopoietic stem cells in
      synergism with interleukin 3 (IL-3), but it has not yet been clarified whether IL
      6 acts directly on the stem cells or not. To investigate the mechanism of the
      synergism between IL-3 and IL-6, we sorted hemopoietic stem cells from untreated
      murine bone marrow cells using a two-laser fluorescence-activated cell sorter
      (FACS). Cells negative for the lymphohemopoietic lineage (lineage-negative, Lin
      ), with a high affinity to wheat germ agglutinin (WGA+), and showing a low
      expression of Thy-1 antigen (Thy-1low) were sorted and analyzed by in vitro and
      in vivo colony formation. This fraction was 0.4% of the total mononuclear bone
      marrow cells. Approximately 25% of these Lin-WGA+Thy-1low cells showed in vitro
      colony formation, whereas approximately 1% of them formed day-8 and day-12 spleen
      colonies. Thus, it appears that the Lin-WGA+Thy-1low cells were a highly enriched
      stem cell population. By FACS clone sorting, single cells were isolated from the
      enriched stem cell fraction and cultured in semisolid or liquid culture systems.
      Addition of IL-6 to methylcellulose medium containing IL-3 did not significantly
      increase the number of colonies. It is thus suggested that the target cells of IL
      3 and IL-6 are the same as those of IL-3. The secondary colony-forming ability of
      primary colonies that developed in the presence of IL-6 and IL-3 was higher than
      that of colonies formed in the presence of IL-3 alone. In correspondence with
      this finding, the numbers of myeloid colonies and spleen colony-forming units
      (CFU-S) were increased by the incubation of these sorted cells for 7 days with IL
      6 and IL-3 when compared with the effect of IL-3 alone. Therefore, it is
      concluded that IL-6 acts directly on hemopoietic stem cells to enhance their
      proliferation.

PMID- 1350249
TI  - In vitro effect of P-glycoprotein (P-gp) modulators on drug sensitivity of
      leukemic progenitors (CFU-L) in acute myelogenous leukemia (AML).
AB  - Cyclosporine A (CyA), a potent reversant of multidrug resistance (mdr), was
      studied for its effects on the sensitivity of leukemic progenitors (leukemia
      colony-forming units, CFU-L) to daunorubicin (DNR) and mitoxantrone. CyA was
      first compared to verapamil and cefoperazone for reversion of mdr in the mdr1+
      cell line K562/DOX. A dramatic increase of sensitivity to 10(-6) M DNR was noted
      with CyA (0.5 and 1 microgram/ml) and verapamil (1 and 5 micrograms/ml), but not
      for cefoperazone (0.3 and 0.6 mg/ml). The sensitivity of K562/DOX to 10(-6) M
      mitoxantrone was also slightly enhanced by CyA. The change in CFU-L drug
      sensitivity in the presence of CyA was then tested in 12 relapsing/resisting
      patients and in 3 untreated patients with acute myelogenous leukemia (AML). No
      change in CFU-L sensitivity to DNR was noted, despite the presence of a subset of
      P-glycoprotein positive (P-gp+) cells in three out of the ten evaluable cases.
      Among the six evaluable cases tested with mitoxantrone and CyA, an increase of
      50% in CFU-L sensitivity to mitoxantrone was noted in one (of three) P-gp+
      patient. These data suggest that the CFU-L in AML rarely expressed the P-gp and
      that other mechanisms of drug resistance could be involved in AML.

PMID- 1350250
TI  - Glutamate-induced action potentials are preceded by regenerative prepotentials in
      rat hippocampal pyramidal cells in vitro.
AB  - (1) The responses of CA1 pyramidal cells to short glutamate pulses (10-50 ms)
      delivered at sensitive spots in the apical dendrites have been analysed by
      intracellular recording. (2) The glutamate pulses elicited stable depolarizing
      responses in a dose- and frequency-dependent manner. (3) When a single action
      potential with a firing probability around 0.5 was elicited, a subtraction
      procedure showed that a slow depolarizing ramp preceded each spike. We call this
      ramp the glutamate-induced prepotential (GluPP). (4) In contrast to the upward
      convex subthreshold depolarization the GluPP was upward concave. (5) The GluPP
      amplitude and time course increased with depolarization of the membrane, a
      phenomenon which appears to be connected to the elevation of action potential
      threshold. (6) The GluPP was regenerative since once started, it ended in an
      action potential. (7) A specific N-methyl-D-aspartate receptor antagonist, DL-2
      amino-5-phosphonovaleric acid (50 microM) reduced the glutamate-induced
      depolarization, but did not affect the form or amplitude of GluPP, once the
      latter was induced. (8) It is concluded that short glutamate pulses elicited
      action potentials through a prepotential mechanism, similar to the slow
      prepotentials induced by long depolarizing current pulses across the soma
      membrane. (9) A possible physiological role for the GluPP is discussed.

PMID- 1350251
TI  - In vitro release of glutamate and aspartate from zebra finch song control nuclei.
AB  - The release of glutamate and aspartate from a song control nucleus, the robust
      nucleus of the archistriatum (RA) of the zebra finch was examined in slice
      preparations. The RA received inputs from two other song control nuclei, the high
      vocal center (HVc) and the lateral magnocellular nucleus of the anterior
      neostriatum (1MAN). The fibers that innervated the RA from either the HVc or the
      1MAN caused calcium-dependent release of glutamate and aspartate after electrical
      stimulation. It is likely that synapses of the RA from the HVc and the 1MAN
      utilize glutamate or aspartate as a neurotransmitter.

PMID- 1350252
TI  - Reaction of astrocytes in the gerbil hippocampus following transient ischemia:
      immunohistochemical observations with antibodies against glial fibrillary acidic
      protein, glutamine synthetase, and S-100 protein.
AB  - An immunohistochemical method was used to study the distribution and changes with
      time of the astrocytic reaction in the gerbil hippocampus following transient
      ischemia. Three markers were investigated with specific antibodies to glial
      fibrillary acidic protein (GFAP), glutamine synthetase (GS), and S-100 protein.
      On Day 2 after ischemia, and more prominently on Day 3, reactive astrocytes were
      intensely stained for GFAP in the hippocampal formation, especially in the CA1
      region and dentate gyrus. This response by astrocytes preceded CA1 pyramidal cell
      degeneration, which became apparent on Day 5. On Day 5, immunoreactive cells were
      not stained as intensely as on Day 3, but cells in the CA1 region and dentate
      gyrus were still more intensely stained than those in normal animals. GS and S
      100 showed similar changes in distribution after ischemia, although the change in
      GS was less prominent: the hilus of the dentate gyrus was most intensely stained.
      Both immunoreactivities seemed to increase rather transiently on Day 2 or 3 and
      to decrease to the initial level on Day 5. The fact that reactive astrocytes
      appeared in CA1 before the onset of visible neural degeneration indicates that
      signals from indisposed neurons may be transmitted to astrocytes for their quick
      functioning. It is also suggested that degenerative changes occur in the dentate
      gyrus and may be involved in the delayed neural death of CA1 pyramidal cells.
      These observations indicate that astrocytes play a role in the neural
      degeneration induced by ischemia and that several types of astrocytes seem to
      react differently.

PMID- 1350253
TI  - Mesostriatal dopaminergic axons transiently express high levels of NILE during
      development.
AB  - The distribution of nerve growth factor-inducible large external (NILE)
      glycoprotein in the developing mesostriatal dopaminergic system was studied by
      immunolabeling prenatal, postnatal, and adult rat brains for both NILE and
      tyrosine hydroxylase (TH). NILE-immunoreactive (NILE-IR) material outlined the TH
      immunoreactive (TH-IR) neurons in the ventral mesencephalon at ages E14, E15, and
      E16 but not at later ages. Fascicles of TH-IR axons in the developing
      mesostriatal dopaminergic tract were strongly immunoreactive for NILE from E15
      through E20. In the postnatal brain, NILE-IR material no longer clearly outlined
      the fascicles of dopaminergic axons as they ran from the mesencephalon to the
      striatum. In the striatum of postnatal and adult rats, NILE-IR material was
      diffusely distributed through the neuropil. Our observations suggest that NILE
      may play a role in guidance of growing dopaminergic axons in the developing
      mesostriatal tract and aggregation of the dopaminergic axons into fascicles.

PMID- 1350254
TI  - A longitudinal study of age-related loss of noradrenergic nerves and lymphoid
      cells in the rat spleen.
AB  - A longitudinal study of sympathetic noradrenergic (NA) innervation of the spleen
      was carried out in 3-, 8-, 12-, 17-, 21-, and 27-month-old Fischer 344 (F344)
      rats using (i) fluorescence histochemistry for localization of norepinephrine
      (NE); (ii) immunocytochemistry (ICC) for localization of tyrosine hydroxylase
      (TH)-positive nerve fibers alone, and in combination with specific markers for T
      and B lymphocytes (OX19 and anti-mu respectively), and macrophages (ED3); and
      (iii) high-performance liquid chromatography with electrochemical detection for
      quantitation of NE. Fluorescence histochemistry revealed extensive loss of NA
      nerve fibers in all compartments of the spleen in 21- and 27-month-old rats. With
      single-label ICC, a decline in TH+ nerve fibers in all compartments of the spleen
      was observed by 17 months of age and became more severe with advancing age; these
      findings suggest that both the rate-limiting enzyme and the transmitter itself
      (NE) are depleted from sympathetic nerves in aged rat spleen. Double-label ICC
      demonstrated the loss of TH+ nerve fibers in spleen from 17-, 21-, and 27-month
      old rats, and a parallel loss of OX19+ T lymphocytes and ED3+ macrophages in
      these cellular compartments. Neurochemical measurement of NE demonstrated a
      decline in NE per wet weight at 27 months of age. The age-related decline in NA
      innervation of spleen and in the density of specific populations of cells of the
      immune system (T lymphocytes and antigen-presenting ED3+ macrophages), that
      follow remarkably similar time courses, supports functional evidence for dynamic
      interactions between the immune system and NA sympathetic nerves in the spleen,
      and further suggests a causal relationship between these age-related phenomena,
      i.e., that age-related immunosenescence promotes sympathetic denervation of the
      spleen which further compromises immune function. This hypothesis, however,
      requires further testing.

PMID- 1350255
TI  - Evidence for different neurochemical contributions to long-term potentiation and
      to kindling and kindling-induced potentiation: role of NMDA and urethane
      sensitive mechanisms.
AB  - Long-term potentiation (LTP) and kindling share a number of features, and it has
      been suggested that LTP might constitute the cellular mechanism of kindling. This
      question was approached by assessing the effect of urethane anesthesia (0.75 or
      1.5 g/kg) or blockade of NMDA receptors by local infusion of DL-2-amino-5
      phosphonovaleric acid (APV; 7.5 micrograms) on LTP, partial kindling, and
      kindling-induced potentiation (KIP) in the perforant path-dentate gyrus circuit
      of the intact hooded rat. Urethane anesthesia attenuated but did not block LTP
      and completely blocked partial kindling and KIP. APV completely blocked LTP but
      did not block partial kindling or KIP in the unanesthetized rat. These results
      suggest that different neurochemical mechanisms can support LTP on the one hand,
      and kindling and KIP on the other. They are consistent with a contribution by
      NMDA-mediated LTP to kindling and KIP, but they indicate that this contribution
      is not crucial for kindling and KIP in this circuit.

PMID- 1350257
TI  - European Association of Gynaecologists and Obstetricians, 6th meeting. Moscow, 5
      8 June, 1991.

PMID- 1350256
TI  - Distribution of 4a-hydroxytetrahydropterin dehydratase in rat tissues. Comparison
      with the aromatic amino acid hydroxylases.
AB  - A 4a-carbinolamine intermediate is generated stoichiometrically during the
      tetrahydrobiopterin-dependent phenylalanine hydroxylation reaction catalyzed by
      phenylalanine hydroxylase. The dehydration of the carbinolamine is catalyzed by
      the enzyme, 4a-hydroxytetrahydropterin dehydratase. We have now examined the
      distribution of the dehydratase activity in various rat tissues by activity
      measurements and by immunoblot analysis to explore the possibility that the
      dehydratase may also play a role in tyrosine and tryptophan hydroxylation. The
      only two tissues that express relatively high dehydratase activity are liver and
      kidney, which are also the only two tissues that express phenylalanine
      hydroxylase activity. The dehydratase activity was generally very low in those
      tissues which contain high levels of tyrosine and tryptophan hydroxylase
      activity, except for the pineal gland. These results suggest that the dehydratase
      may not play an important role in the regulation of the synthesis of those
      neurotransmitters which are derived from the hydroxylated aromatic amino acids.

PMID- 1350258
TI  - Variability of the insulin gene in American blacks with NIDDM. Analysis by single
      strand conformational polymorphisms.
AB  - Previous studies of the insulin gene--utilized restriction-fragment--length
      polymorphisms as markers for potential mutations at this locus. This indirect
      type of analysis could not define the number of variants that might exist within
      the structural portions and regulatory regions of the gene in non-insulin
      dependent diabetes mellitus (NIDDM) patients. New technology has allowed us to
      examine insulin genes at the single nucleotide level from 100 American black
      NIDDM patients. Genomic DNA from patients was amplified by the polymerase chain
      reaction with primers flanking four regions of the gene: 1) the proximal promoter
      from positions -182 to 42 (including most of exon 1); 2) exon 1 from 14 to 259,
      which included the rest of exon 1 and all of the 1st intron; 3) exon 2 from 216
      to 452; and 4) exon 3 from 1188 to 1433. One of the primers in each reaction was
      32P-end labeled and the resulting products denatured into single strands and
      electrophoresed on nondenaturing sequencing gels such that mobility was a
      function of composition and size (single-strand conformational polymorphism or
      SSCP). Under these conditions, single-base changes in fragments up to 245
      nucleotides were detected. Analysis of the proximal promoter region revealed
      several SSCP patterns in individuals. Direct genomic sequencing of DNA
      representative of these patterns showed the presence of a common C to G change at
      position -56 and a C deletion at position -90 in three patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1350259
TI  - Colocalization of GLUT2 glucose transporter, sodium/glucose cotransporter, and
      gamma-glutamyl transpeptidase in rat kidney with double-peroxidase
      immunocytochemistry.
AB  - Glucose is reabsorbed from the glomerular filtrate in the proximal segment of the
      renal tubule in two stages. The first stage is uphill transport across the brush
      border membrane by Na(+)-glucose cotransport and the second stage is downhill
      transport across the basolateral membrane by facilitated diffusion. Genes for
      both a renal Na(+)-glucose cotransporter (SGLT1) and a renal facilitated glucose
      transporter (GLUT2) have been cloned and sequenced. To examine whether SGLT1 and
      GLUT2 colocalize to the same tubular epithelial cells in rat kidney, double
      immunoperoxidase studies with dual chromogens and paraformaldehyde perfusion
      fixed frozen sections of rat kidney were performed. Antipeptide antisera were
      prepared against rat GLUT2 (amino acids 510-522) and rabbit SGLT1 (amino acids
      402-420). Proximal tubules were identified immunocytochemically with an antiserum
      raised against a synthetic peptide corresponding to the 21 amino acids at the
      COOH-terminal of the heavy chain of rat gamma-glutamyl transpeptidase, which is a
      proximal tubule-specific enzyme. The anti-GLUT2 antiserum strongly stained the
      basolateral membrane of 46% of cortical tubules, whereas the SGLT1 antiserum
      stained the brush border of 56% of the cortical tubules. The gamma-glutamyl
      transpeptidase antiserum also stained the brush border of 51% of the cortical
      tubules. GLUT2 and SGLT1 colocalized to 40% of cortical epithelium, but 16% of
      cortical epithelial cells were immunopositive for brush border SGLT1 and
      immunonegative for basolateral GLUT2. These gamma-glutamyl transpeptidase
      staining results suggest that at least 50% of the tubules in the cortex are
      proximal tubules and that SGLT1 and GLUT2 colocalize to most proximal tubules.
      The fact that SGLT1 antiserum immunoreacted with tubules unreactive to the GLUT2
      antiserum suggests that either the SGLT1 epitope is conserved on a related brush
      border protein or that there is another GLUT transporter responsible for the exit
      of sugar from these proximal tubule cells.

PMID- 1350260
TI  - Immunochemical localization of aminopeptidase M in the alimentary tract of the
      guinea pig and rat.
AB  - Aminopeptidase M (APM) was localized in the kidney and alimentary tract of guinea
      pigs and rats by indirect immunohistochemistry. APM was detected in the brush
      border of the epithelium of the proximal convoluted tubule of the kidney and of
      the small intestine, and it was localized to cells scattered throughout lymphoid
      tissue in the small intestine and colon. The gastric mucosa was unstained. APM
      was localized to numerous fibers supplying the myenteric plexus of the stomach,
      small intestine, and colon. The submucosal plexus was sparsely supplied by
      immunoreactive fibers. Occasional cell bodies were stained in the myenteric
      plexus. Staining was abolished by preabsorption of the primary antibody with APM.
      APM was characterized in membranes prepared from the muscle and mucosa of the
      guinea pig and rat stomach, small intestine, and colon by Western blotting. The
      major immunoreactive protein identified in membranes prepared from all tissues
      had an apparent molecular weight of 140, corresponding to the monomer of APM. In
      the brush border APM has a digestive function, whereas in neural tissue it may
      degrade and inactivate neuropeptides.

PMID- 1350261
TI  - c-Ki-ras mutations in dysplastic fields and cancers in ulcerative colitis.
AB  - A sensitive restriction fragment length polymorphism assay and DNA sequencing
      were used to detect c-Ki-ras mutations in 56 specimens of colonic epithelium from
      18 patients with chronic ulcerative colitis. Mutations were not detected in
      biopsy specimens that were negative or indefinite for dysplasia. In 4 of 8
      patients with high-grade dysplasia, a c-Ki-ras codon 12 or 13 mutation was
      detected. In three colectomy specimens, a wide area of dysplastic cells (greater
      than 10 cm2) contained a specific ras mutation. In two of these specimens, an
      invasive cancer contained a c-Ki-ras mutation identical to that found in adjacent
      dysplastic epithelium. These studies indicate that mutations of c-Ki-ras may be
      an excellent molecular genetic marker to map dysplastic fields and invasive
      cancer in ulcerative colitis.

PMID- 1350262
TI  - Genetic and blood coagulation characterization of "Swedish" families with von
      Willebrand's disease types I and III: new aspects of heredity.
AB  - Twenty-five patients with von Willebrand's disease (vWD) type III were analysed
      with regard to blood coagulation variables and possible deletions. Nine of the
      probands and their families were further investigated with DNA linkage analyses.
      Different patterns of heredity can be suggested in our families with vWD type
      III, on the basis of blood coagulation analyses. The findings suggest
      homozygosity in five families and the possibility of compound heterozygosity or a
      new mutation in the proband in three families. The linkage analyses confirm the
      results of the coagulation analyses. The segregation of the von Willebrand factor
      (vWF) gene can be followed in the families, and carrier diagnosis can be made in
      several of the probands' relatives. The possibility of large deletions in the vWF
      gene of the probands and their parents was investigated with probes representing
      the whole vWF cDNA. No deletions were found.

PMID- 1350263
TI  - Isolation and mapping of polymorphic cosmid clones used for sublocalization of
      the multiple endocrine neoplasia type 1 (MEN1) locus.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is characterized by neoplasia of the
      parathyroids, the pancreas, and the pituitary. Tumorigenesis involves unmasking
      of a recessive mutation at the MEN1 locus, which has been mapped to the
      centromeric part of chromosomal region 11q. In order to localize the MEN1 gene
      further and to make its isolation possible, a number of new markers were
      isolated. Two radiation-reduced somatic cell hybrids were identified that only
      contained markers close to and flanking the MEN1 region. DNA from these hybrids
      was used for the construction of a cosmid library, and clones containing human
      inserts were isolated. In addition, cosmid clones were isolated for locus
      expansion of 7 other markers that were mapped to the 11q12-13.2 region. The 33
      newly isolated clones together with 25 previously published markers from this
      region were analyzed in a panel of radiation-reduced somatic cell hybrids. From
      the hybridization pattern, the region was divided into 11 parts. New restriction
      fragment length polymorphisms were identified in 7 of the newly isolated cosmid
      clones and in one plasmid. These were then used to sublocalize meiotic cross
      overs more precisely in two MEN1 families, thus refining the mapping of the
      disease gene.

PMID- 1350264
TI  - Wiskott-Aldrich syndrome carrier detection with the hypervariable marker M27
      beta.
AB  - Whole-blood cells of obligate carriers of the X-linked Wiskott-Aldrich syndrome
      (WAS) exhibit nonrandom inactivation of the X-chromosomes. However, because of
      the limited polymorphism of the probes available, the X-methylation pattern can
      only be determined in a restricted proportion of females. We thus analysed a
      large set of normal females and members of WAS families, using the recently
      described marker M27 beta, which detects the hyperpolymorphic locus DXS255. The
      probe was used to detect differences in methylation between the active and
      inactive X-chromosome, and the findings were compared with the pattern obtained
      using the well-documented probes from the 5' end of the PGK and HPRT genes. All
      the normal females were found to use either X-chromosome randomly, and there was
      complete correlation between the three probes in the populations studied.
      Segregation analysis performed with M27 beta and other related markers in the WAS
      families was fully in accordance with the X-inactivation data. The use of M27
      beta, for both X-inactivation and segregation analysis of WAS kindreds, provides
      a basis for genetic counselling in the majority of families, including those with
      no surviving males.

PMID- 1350265
TI  - The human fumarylacetoacetase gene: characterisation of restriction fragment
      length polymorphisms and identification of haplotypes in tyrosinemia type 1 and
      pseudodeficiency.
AB  - Deficiency of human fumarylacetoacetase (FAH) activity results in hereditary
      tyrosinemia type I. Using the restriction enzymes BglII, KpnI and StuI and a 1.3
      kb cDNA probe for the FAH gene, we have found 6 restriction fragment length
      polymorphisms (RFLPs). These RFLPs were utilised in 3 tyrosinemia families in
      which one or both parents are carriers of both a tyrosinemia and a
      pseudodeficiency gene for FAH. Full information was obtained in two of these
      families. The polymorphisms identified 6 haplotypes. The haplotype distribution
      was significantly different in 32 unrelated tyrosinemia patients compared with a
      reference population of 100 individuals. The combined polymorphism information
      content was 0.77.

PMID- 1350266
TI  - Prenatal diagnosis of familial hypercholesterolemia caused by the "Lebanese"
      mutation at the low density lipoprotein receptor locus.
AB  - Here, we report the prenatal diagnosis of familial hypercholesterolemia in a
      Christian-Arab family that carries the "Lebanese" mutation, a single base
      substitution that creates a HinfI restriction site, at the low density
      lipoprotein (LDL) receptor locus. Polymerase chain reaction amplification and
      restriction analysis were performed on genomic DNA extracted from a chorionic
      villus sample. In conjunction with karyotype analysis, the fetus was identified
      as a heterozygous female. Analysis of LDL receptor restriction fragment length
      polymorphisms confirmed the presence of a male parent marker and revealed that
      the fetus inherited the mutant gene from its mother. This technique offers a
      simple and rapid diagnostic tool that can be carried out at an early stage of
      gestation. It is recommended for families and population groups with molecularly
      defined LDL receptor mutations.

PMID- 1350267
TI  - A possible association between basic amino acids of position 13 of DRB1 chains
      and autoimmune hepatitis.
AB  - Fifty-one patients with autoimmune hepatitis have been studied for HLA
      association by conventional serology and also by modified polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping. HLA-DR4
      was significantly associated with autoimmune hepatitis (46 of 51 patients,
      90.2%). DNA typing of the DRB1 gene for 43 DR4-positive patients by using the PCR
      RFLP technique revealed that of 43 patients, 33 had DRB1*0405 (Dw15), five had
      DRB1*0406 (DwKT2), four had DRB1*0403 (Dw13a), two had DRB1*0401 (Dw4), two of 43
      had DRB1*0407 (Dw13b) and one had DRB1*0408 (Dw14b). Thus, there was no
      significant difference in Dw frequencies between DR4-positive patients and DR4
      positive healthy subjects. These findings suggest that the DR4-specific sequence
      (Val 11 and His 13 at amino acid positions 11 and 13, respectively), but not
      particular Dw-associated DR4 sequence, in the first domain of the DRB1 chain
      contributes to susceptibility to autoimmune hepatitis among Japanese.
      Interestingly, all five of the DR4-negative patients had the DR2 specificity
      (DRB1*1502 or 1601). Taken together, these results imply that the basic amino
      acids at position 13, which is present only on the DR2 and DR4 B1 molecules (Arg
      on DR2 and His on DR4), are most important for determining the predisposition to
      autoimmune hepatitis.

PMID- 1350268
TI  - DRw52-group haplotypes are frequent acceptors of DRw15-Dw2 DQ genes in DQA1-DRB1
      recombination.

PMID- 1350269
TI  - Signals delivered via the Qa-2 molecule can synergize with limiting anti-CD3
      induced signals to cause T lymphocyte activation.
AB  - Qa-2 is a glycolipid anchored, MHC encoded class I molecule expressed at high
      levels on all murine peripheral T lymphocytes. Anti-Qa-2 antibodies have
      previously been found to stimulate T cells to proliferate in the presence of
      crosslinking antibody and PMA. We have examined the effect of anti-Qa-2
      antibodies on T cells stimulated with a suboptimal concentration of immobilized
      anti-CD3. When anti-Qa-2 antibodies were co-immobilized with limiting anti-CD3,
      in the absence of PMA, a clear augmentation of T cell proliferation was seen.
      Interestingly, the co-stimulatory anti-Qa-2 antibodies could be directed against
      epitopes mapped to either the alpha 3 or the alpha 1/alpha 2 Qa-2 domains. As was
      the case with activation induced by soluble/crosslinked anti-Qa-2 antibodies plus
      PMA, CD8+ T cells were less able to be costimulated with anti-Qa-2 antibodies
      than CD4+ cells. Surprisingly, Ca2+ mobilization was only seen when two anti-Qa-2
      antibodies reactive to separate structural domains were co-crosslinked on the
      surface of Indo-1 loaded T cells with a suboptimal concentration of anti-CD3.
      Collectively these results raise questions regarding the mechanism of Qa-2
      mediated signaling and its potential role in T cell activation.

PMID- 1350270
TI  - Regulation of receptor-mediated shape change in astroglial cells.
AB  - Activation of adenylate cyclase in astroglial cells in culture results in a rapid
      change in cell shape that appears to occur by the active movement of cytoplasm
      from peripheral cell regions to the perinuclear space with processes being formed
      along regions that remain extended. Three series of experiments were designed to
      determine how shape change occurred. First, the Ca(2+)-dependency of shape change
      was determined by reducing intracellular Ca2+ concentrations to less than or
      equal to 50 nM or increasing intracellular Ca2+ concentrations to greater than or
      equal to 1 microM. Neither of these changes significantly affected the rate of
      receptor-mediated shape change. Second the role that longer-lived, acetylated
      microtubules play in receptor-mediated shape change was assessed by visualizing
      microtubules using a polyclonal antibody to brain 6S tubulin or a monoclonal
      antibody to oligomers of tubulin to monitor total tubulin distribution and a
      monoclonal antibody to acetylated tubulin to describe the distribution of these
      microtubules. Three-dimensional distribution of microtubules was observed by
      optical sectioning of cultures using a laser scanning confocal imaging system.
      The distribution of acetylated tubules in control cells was similar to that
      observed with the antibodies to tubulin. Following treatment with 100 nM
      isoproterenol to stimulate shape change, there was a dramatic redistribution of
      microtubules; however, the distribution of acetylated tubules was again similar
      to the total microtubules. Analysis of the optical sections recorded using the
      confocal attachment revealed that while control cells were relatively flat (cell
      height = 4 microns), the perinuclear region of isoproterenol-treated cells
      extended much higher above the substrate (cell height = 13 microns). Third, the
      role of microtubule assembly and disassembly were assessed using colchicine and
      taxol. Results from these experiments suggest that microtubule reassembly is
      necessary for receptor-mediated shape change. Control experiments indicated that
      colchicine or taxol treatment did not inhibit either cAMP synthesis or another
      cAMP-dependent process, receptor-mediated taurine release. Together these results
      indicate that receptor-mediated shape change in astroglial cells occurs by a
      Ca(2+)-independent mechanism that results in active movement of cytoplasm to the
      perinuclear region. This process is dependent on microtubule reassembly
      suggesting that shape change may occur by active movement of material along
      microtubules or by microtubule redistribution.

PMID- 1350271
TI  - Co-cultures of microglia and astrocytes from kainic acid-lesioned adult rat
      hippocampus: effects of glutamate.
AB  - The long-standing question concerning the direct actions of glutamate on the
      membrane potential of astroglial cells in the central nervous system was
      addressed using the in vitro kainic acid-lesioned hippocampal slice preparation
      and primary cell co-cultures of astrocytes and microglia derived from such
      lesions. The ultrastructure of the lesioned hippocampus was examined to aid in
      the identification of the cells appearing in culture. In culture, microglia
      appeared as flat cells, less than 1 micron in thickness at the edge of the cell,
      but thicker (about 5 microns) near the nucleus. The cytoplasm was packed with
      granular inclusions. Microglia appeared in two morphological forms, amoeboid and
      ramified. The amoeboid form was characterized by a cell body with a single
      process, and was always observed 1 day after starting the cell culture. Such
      cells became less frequent after 1 week in culture. The ramified form appeared as
      a rounded cell, devoid of processes, and were frequently observed in older
      cultures (greater than 1 week). Microglia did not round up after exposure to
      dibutyrylcyclic adenosine monophosphate (cAMP), and did not stain for glial
      fibrillary acidic protein (GFAP). An ultrastructural examination of the lesion
      demonstrated that microglia were present and that they contained many cytoplasmic
      granules similar to lipofuscin-containing granules. No filaments were observed in
      the cytoplasm of microglia. By contrast, the cytoplasm of astrocytes in culture
      had far fewer granules, rounded up to dibutyryl-cAMP, exhibited multiple
      processes, and stained for GFAP. In slices, astrocytes had no lipofuscin
      containing granules, but numerous cytoplasmic filaments were present.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1350272
TI  - Serotonin promotes region-specific glial influences on cultured serotonin and
      dopamine neurons.
AB  - To test the hypothesis that glia mediate interactions between embryonic
      serotonergic (5-HT) neurons and dopamine neurons, we studied the effects of 5-HT
      in co-cultures of E14 raphe neurons of mesencephalic dopamine neurons and radial
      glia/astrocytes derived from the same (homotypic) or opposite (heterotypic) brain
      region using a dose (10(-5) M) that would produce 5-HT uptake into glial cells as
      well as activate 5-HT receptors. Morphometric analysis of 5-HT and tyrosine
      hydroxylase (TH) immunoreactive neurons revealed regional differences in the
      effects of 5-HT (and nialamide) on survival, cell soma size, and dendrite-like
      neurite outgrowth in neuronal-glial co-cultures. In general, 5-HT had more
      significant effects on both types of monoamine neuron when they were cultured
      with mesencephalic glia (GSN). Stimulatory effects of 5-HT on growth of TH
      neurons in GSN cultures suggest that developing raphe axons, which reach the
      mesencephalon during the early differentiation of these neurons, may enhance the
      influence of local glial-derived trophic factors. Likewise, the promotion of 5-HT
      neuronal survival in these cultures suggests that glial factors in the
      mesencephalon may contribute to the support of 5-HT neurons in addition to the
      influences of raphe glia. The inhibitory effects of 5-HT on neurite outgrowth by
      raphe neurons in GSN co-cultures indicates enhanced sensitivity of these neurons
      to the inhibitory effects of 5-HT in the presence of mesencephalic glia. The
      region-specific effects of 5-HT and nialamide in glial co-cultures suggest that
      raphe and mesencephalic glia may express different capacities for 5-HT uptake,
      receptors, and/or monoamine oxidase (MAO) activities. These characteristics could
      be important for the specificity of growth-regulatory influences of glial cells
      on the development of brain monoamine neurons.

PMID- 1350274
TI  - Characterization of the heat shock response in Brucella abortus and isolation of
      the genes encoding the GroE heat shock proteins.
AB  - In an effort to define the heat shock response in the bovine intracellular
      pathogen Brucella abortus, a rough variant lacking extensive lipopolysaccharide
      was pulse-labeled with [35S]methionine following exposure to elevated
      temperatures. The major heat shock proteins observed following sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and autoradiography migrate at 70, 62,
      18, and 10 kDa. The maximum response was observed between 42 and 46 degrees C and
      within 2 to 3 h of the shif in temperature and varied slightly for the different
      proteins. Accumulation of the 62-kDa heat shock protein (62-kDa Hsp) was observed
      to continue for up to 5 h following the shift in temperature. In an effort to
      better define the heat shock response and its potential relationship with
      protective immunity, genes encoding the major heat shock proteins were isolated
      from recombinant libraries constructed from B. abortus S19 and S2308 and
      sequenced. The 62-kDa Hsp shares more than 60% amino acid homology with members
      of the GroEL family and is immunoprecipitated with polyclonal antibodies to
      Escherichia coli GroEL and monoclonal antibodies to mycobacterial Hsp 65. Western
      blot (immunoblot) analysis with pooled sera from vaccinated and infected cattle
      revealed that the 62-kDa Hsp is a predominantly recognized antigen. The roles of
      these gene products during environmental stress and in protective immunity
      against brucellosis are under investigation.

PMID- 1350273
TI  - Aggregative adherence fimbriae I of enteroaggregative Escherichia coli mediate
      adherence to HEp-2 cells and hemagglutination of human erythrocytes.
AB  - Strains of enteroaggregative Escherichia coli (EAggEC) have been implicated in
      several studies as important agents of persistent diarrhea among infants in the
      developing world. We have previously shown that the aggregative adherence (AA)
      property of EAggEC is associated with the presence of a 60-MDa plasmid which
      confers AA when introduced into E. coli HB101. Here, we report the cloning of the
      AA determinant from EAggEC strain 17-2 into the 21.5-kb cosmid vector pCVD301.
      TnphoA mutagenesis of the AA cosmid clone pJPN31 implicated an AA region of
      approximately 12 kb. Transmission electron microscopy of HB101 (pJPN31) revealed
      the presence of bundle-forming fimbriae, which were absent in AA- TnphoA
      insertion mutants. The presence of these fimbriae, AA, and hemagglutination (HA)
      of human erythrocytes were all concurrently lost by single-insertion mutations. A
      14-kDa protein was seen on polyacrylamide gel electrophoresis and Western
      blotting (immunoblotting) of surface shear preparations from fimbriated clones.
      Twelve of nineteen volunteers fed EAggEC 17-2 developed rises in antibodies to
      the 14-kDa protein as determined by Western blot. We have termed the cloned
      bundle-forming fimbriae aggregative adherence fimbriae I (AAF/I); positivity with
      a previously described EAggEC probe and human erythrocyte HA appear to correlate
      with the presence of AAF/I.

PMID- 1350275
TI  - Functional expression of heterologous fimbrial subunits mediated by the F41, K88,
      and CS31A determinants of Escherichia coli.
AB  - F41, K88, and CS31A are fimbrial adhesins associated with enterotoxigenic
      Escherichia coli. These adhesins are distinct from one another in the composition
      of their structural subunits and the adherence characteristics associated with
      their expression. Despite these differences, extensive homology exists between
      the genetic determinants mediating the expression of these adhesins, extending
      throughout the region of each determinant encoding the accessory proteins
      involved in adhesin biogenesis. This suggests that the regulatory and assembly
      systems mediating expression of these adhesins may be functionally
      interchangeable. In the present study we demonstrated that the accessory systems
      of the F41, K88, and CS31A determinants are able to mediate the functional
      expression of heterologous fimbrial subunit proteins. Plasmid constructs
      containing the isolated fimbrial subunit gene of the F41 or CS31A determinant
      were prepared and introduced into E. coli harboring the F41, K88, and CS31A
      accessory genes contained on compatible plasmid vectors. The ability of each of
      the three accessory systems to mediate stable expression of the F41 or CS31A
      fimbrial subunit peptide was demonstrated by Western blot (immunoblot) analysis.
      Functional expression of the F41 or CS31A subunit on the bacterial cell surface
      was demonstrated by the ability of these proteins to confer mannose-resistant
      hemagglutination of human erythrocytes or in vitro adherence to epithelial cells,
      respectively. The accessory system of an unrelated adhesin determinant, F1845,
      did not mediate functional expression of F41 adherence. Taken together, these
      data indicate that the genetic determinants mediating expression of the F41, K88,
      and CS31A adhesins are members of a closely related family and suggest that a
      mechanism exists in the family for the more rapid divergence of genes encoding
      antigenic and adhesive determinants.

PMID- 1350276
TI  - Neurotransmitters as neurotrophic factors: a new set of functions.
AB  - At the start of this review, factors were deemed trophic if they stimulated
      mitosis, permitted neural cell survival, promoted neurite sprouting and growth
      cone motility, or turned on a specific neuronal phenotype. The in vitro evidence
      from cell cultures is overwhelming that both neurotransmitters and neuropeptides
      can have such actions. Furthermore, the same chemical can exert several of these
      effects, either on the same or on different cell populations. Perhaps the most
      striking example is that of VIP, which can stimulate not only mitosis, but also
      survival and neurite sprouting of sympathetic ganglion neuroblasts (Pincus et
      al., 1990a,b). The in vivo data to support the in vitro experiments are starting
      to appear. A role for VIP in neurodevelopment is supported by in vivo studies
      that show behavioral deficits produced in neonatal rats by treatment with a VIP
      antagonist (Hill et al., 1991). The work of Shatz' laboratory (Chun et al., 1987;
      Ghosh et al., 1990) suggests that neuropeptide-containing neurons, transiently
      present, serve as guideposts for thalamocortical axons coming in to innervate
      specific cortical areas. Along similar lines, Wolff et al. (1979) demonstrated
      gamma-aminobutyric acid-accumulating glia in embryonic cortex that appeared to
      form axoglial synapses and suggested the possibility that gamma-aminobutyric acid
      released from the glia might play a role in synaptogenesis by increasing the
      number of postsynaptic thickenings. Meshul et al. (1987) have provided evidence
      that astrocytes can regulate synaptic density in the developing cerebellum. The
      work of Zagon and McLaughlin (1986a,b, 1987) has shown that naltrexone, an
      antagonist of the endogenous opioid peptides, affects both cell number and
      neuronal sprouting. Lauder's laboratory (Lauder et al., 1982) has shown a role
      for 5-HT in regulation of the proliferation of numerous cell types. These studies
      illustrate another important point, that neurotransmitters and neuropeptides
      function in communication not only between neurons, but also between neurons and
      glial cells, and between glial cells. Given that astrocytes can express virtually
      all of the neural receptors and can produce at least some of the
      neurotransmitters and neuropeptides, they must now be considered equal partners
      in the processes of intercellular communication in the nervous system, including
      the trophic responses. The actions of neurotransmitters and neuropeptides have to
      be considered in terms of a broad spectrum of actions that range from the trophic
      actions described in this review, to the classic transmitter actions, to
      potential roles in neurotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1350277
TI  - The retinoblastoma gene product suppresses neu oncogene-induced transformation
      via transcriptional repression of neu.
AB  - The retinoblastoma susceptibility gene (Rb) is a tumor suppressor gene involved
      in the etiology of many types of human cancers. However, the molecular mechanisms
      involved in tumor suppression by Rb are largely unknown. The neu gene is a
      dominant transforming oncogene and a member of the growth factor receptor
      tyrosine kinase gene family. Both inactivation of the Rb gene and overexpression
      of the neu gene are involved in human breast and lung cancers. Therefore, it is
      of interest and importance to investigate the potential interactions between Rb
      and neu. Here we show that Rb suppresses neu-induced transformation by focus
      formation assays. This transformation suppression by Rb was further shown to be
      due to transcriptional repression of neu using Rb expressing effector plasmid and
      neu promoter-chloramphenicol acetyltransferase reporter gene. The cis-acting
      element conferring Rb-mediated repression was mapped to a recently identified
      novel enhancer in the neu promoter. The data indicate that the growth factor
      receptor neu is a target for the Rb gene product and transcriptional repression
      of a dominant oncogene expression may be one of the molecular mechanisms of Rb
      mediated tumor suppression.

PMID- 1350278
TI  - The physical and enzymatic properties of Escherichia coli recA protein display
      anion-specific inhibition.
AB  - The enzymatic activities of Escherichia coli recA protein are sensitive to ionic
      composition. Here we report that sodium glutamate (NaGlu) is much less inhibitory
      to the DNA strand exchange, DNA-dependent ATPase, and DNA binding activities of
      the recA protein than is NaCl. Both joint molecule formation and complete
      exchange of DNA strands occur (albeit at reduced rates) at NaGlu concentrations
      as high as 0.5 M whereas concentrations of NaCl greater than 0.2 M are sufficient
      for complete inhibition. The single-stranded DNA (ssDNA)-dependent ATPase
      activity is even less sensitive to inhibition by NaGlu; ATP hydrolysis stimulated
      by M13 ssDNA is unaffected by 0.5 M NaGlu and is further stimulated by E. coli
      ssDNA binding protein approximately 2-fold. Finally, NaGlu has essentially no
      effect on the stability of recA protein-epsilon M13 DNA complexes, with
      concentrations of NaGlu as high as 1.5 M failing to dissociate the complexes.
      Surprisingly, NaGlu also has little effect on the concentration of NaCl required
      to disrupt the recA protein-epsilon M13 DNA complex, demonstrating that
      destabilization is dependent on both the concentration and type of anionic rather
      than cationic species. Quantitative analysis of DNA binding isotherms establishes
      that the intrinsic binding affinity of recA protein is affected by the anionic
      species present and that the cooperativity parameter is relatively unaffected.
      Consequently, the sensitivity of recA protein-ssDNA complexes to disruption by
      NaCl does not result from the competitive effects associated with cation
      displacement from the ssDNA upon protein binding but rather results from anion
      displacement upon complex formation. The magnitude of this anion-specific effect
      on ssDNA binding is large relative to that of other nucleic acid binding
      proteins.

PMID- 1350279
TI  - Glutamate-malate metabolism in liver mitochondria. A model constructed on the
      basis of mitochondrial levels of enzymes, specificity, dissociation constants,
      and stoichiometry of hetero-enzyme complexes.
AB  - The level of aspartate aminotransferase in liver mitochondria was found to be
      approximately 140 microM, or 2-3 orders of magnitude higher than its dissociation
      constant in complexes with the inner mitochondrial membrane and the high
      molecular weight enzymes (M(r) = 1.6 x 10(5) to 2.7 x 10(6)) carbamyl-phosphate
      synthase I, glutamate dehydrogenase, and the alpha-ketoglutarate dehydrogenase
      complex. The total concentration of aminotransferase-binding sites on these
      structures in liver mitochondria was more than sufficient to accommodate all of
      the aminotransferase. Therefore, in liver mitochondria, the aminotransferase
      could be associated with the inner mitochondrial membrane and/or these high
      molecular weight enzymes. The aminotransferase in these hetero-enzyme complexes
      could be supplied with oxalacetate because binding of aminotransferase to the
      high molecular weight enzymes can enhance binding of malate dehydrogenase, and
      binding of both malate dehydrogenase and the aminotransferase facilitated binding
      of fumarase. The level of malate dehydrogenase was found to be so high (140
      microM) in liver mitochondria, compared with that of citrate synthase (25 microM)
      and the pyruvate dehydrogenase complex (0.3 microM), that there would also be a
      sufficient supply of oxalacetate to citrate synthase-pyruvate dehydrogenase.

PMID- 1350281
TI  - The p88 molecular chaperone is identical to the endoplasmic reticulum membrane
      protein, calnexin.
AB  - We previously described a novel molecular chaperone (designated p88) that
      participates in the assembly of murine class I histocompatibility molecules
      (Degen, E., and Williams, D. B. (1991) J. Cell Biol. 112, 1099-1115). Our
      findings suggest that p88 may either promote proper assembly of class I molecules
      or retain them, probably within the endoplasmic reticulum (ER), until assembly of
      the ternary complex of heavy chain, beta 2-microglobulin, and peptide ligand is
      complete. In this report, we compare p88 to calnexin, a calcium-binding 90-kDa
      phosphoprotein of the ER membrane (Wada, I., Rindress, D., Cameron, P. H., Ou, W.
      J., Doherty, J.-J., II, Louvard, D., Bell, A.W., Dignard, D., Thomas, D. Y., and
      Bergeron, J. J. M. (1991) J. Biol. Chem. 266, 19599-19610). We show that p88 and
      calnexin share antigenic epitopes defined by a polyclonal anti-calnexin
      antiserum. Furthermore, both proteins were immunoprecipitated in association with
      an intracellularly retained variant of the class I H-2Kb molecule. Since p88 and
      calnexin were also indistinguishable by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis, were resistant to digestion with endoglycosidase H, and
      exhibited virtually identical patterns of peptide fragments following digestion
      with either V8 protease or trypsin, we conclude that p88 and calnexin represent
      the same protein. The identification of the p88 chaperone as a phosphorylated,
      calcium-binding protein of the ER membrane suggests possible means whereby its
      interaction with class I molecules may be regulated.

PMID- 1350280
TI  - Energy-dependent accumulation of daunorubicin into subcellular compartments of
      human leukemia cells and cytoplasts.
AB  - Anthracycline accumulation was evaluated by flow cytometry or radiolabeled drug
      assays in cells and cytoplasts (enucleated cells) prepared from parental and
      multidrug-resistant human K562 leukemia cells. Treatment with energy inhibitors,
      such as dinitrophenol (DNP) or sodium azide/deoxyglucose, led to a marked
      decrease in daunorubicin accumulation in parental cells and cytoplasts. Another
      ionophore, monensin, also caused a significant decrease in daunorubicin
      accumulation; however, ATPase inhibitors ouabain, vanadate, and N-ethylamaleimide
      had little or no effect. The lysosomatropic agents chloroquine and methylamine
      caused a moderate decrease in anthracycline accumulation. Fluorescence microscopy
      showed that the DNP-sensitive daunorubicin uptake occurred in a nonnuclear
      subcellular compartment. Studies using increasing daunorubicin concentrations
      demonstrated fluorescence quenching that occurred in the nonnuclear, DNP
      sensitive compartment. The effect of inhibitors on the accumulation of rhodamine
      123 and acridine orange strongly implicated lysosomes as the principal
      compartment of this inhibitable daunorubicin accumulation. Cytoplasts from P
      glycoprotein containing multidrug-resistant K562 cells demonstrated a verapamil
      reversible, decreased daunorubicin accumulation that was observed in resistant
      whole cells. Verapamil pretreatment of cytoplasts from resistant cells revealed
      the subcellular DNP-sensitive uptake present in parental cytoplasts. These
      studies demonstrate that cytoplasts are an effective means to study drug
      transport in mammalian cells without nuclear drug binding. Parental K562 cells
      and cytoplasts exhibit an energy-dependent accumulation of daunorubicin into
      cytoplasmic organelles that is also present in resistant cells and cytoplasts
      when P-glycoprotein mediated efflux is inhibited.

PMID- 1350282
TI  - Dietary regulation of stearoyl-CoA desaturase 1 gene expression in mouse liver.
AB  - Expression of the murine liver stearoyl-CoA desaturase gene (SCD1) is induced
      upon feeding fasted mice a fat-free, high carbohydrate diet (Ntambi, J. M.,
      Buhrow, S. A., Kaestner, K. H., Christy, R. J., Sibley, E., Kelly, T. J., and
      Lane, M.D. (1988) J. Biol. Chem. 263, 17291-17300). In the present study, SCD1
      specific RNA riboprobes and cDNA probes were used to study the mechanism for the
      induction of SCD1 mRNA. Based on the time course of induction, the SCD1 mRNA
      increased from 2-fold within 6 h to 45-fold within 36 h. Nuclear run-on
      transcription studies showed that the accumulation of SCD1 mRNA after refeeding
      starved mice a fat-free, high carbohydrate diet was a consequence of the
      transcriptional activation of the SCD1 gene. The SCD1 mRNA level decreased
      rapidly (t1/2 = approximately 4 h) within 24 h when mice fed the fat-free, high
      carbohydrate diet were switched to a regular chow diet. Furthermore, when the fat
      free diet was supplemented with triacylglycerides containing polyunsaturated
      fatty acids, the transcription of the SCD1 gene and the induction of the SCD1
      mRNA were significantly blunted. Triacylglycerides containing saturated and
      monounsaturated fatty acids were without dramatic effects. In contrast, synthesis
      of liver albumin mRNA was little affected by any of these dietary variations,
      indicating that the observed changes in the transcription of the SCD1 gene and
      mRNA levels were specific. These data demonstrate that both dietary carbohydrates
      and polyunsaturated fatty acids or their metabolites directly or indirectly
      regulate the expression of the SCD1 gene in mouse liver.

PMID- 1350283
TI  - Cold stress response in patients with severe burns after beta-blockade.
AB  - Adrenergic receptor blockade has been shown to be of benefit in the treatment of
      adverse cardiovascular changes in patients with burns during the hypermetabolic
      phase. This article examines the stress response to cold exposure in adults and
      children with 33% to 95% total body surface area burns with and without beta
      blockade. Resting energy expenditures were measured by indirect calorimetry; the
      test subjects were exposed to mean temperatures of 27.5 degrees C (room
      temperature) or 24.6 degrees C (cold). The mean resting energy expenditure at
      ambient room temperature in patients with burns without beta-blockade was 1411 +/
      70 kcal/m2/day (mean +/- SEM). This value was 142% of that predicted for normal
      control subjects without burns. When placed in a cold temperature, patients with
      burns significantly increased their resting energy expenditures by 160% of
      predicted values, whereas patients with similar burns and beta-blockade increased
      their resting energy expenditures by 156%. Adults with septic burns had a mean
      resting energy expenditure 198% of the predicted value. These patients did not
      significantly increase their resting energy expenditures when they were exposed
      to cold either with or without beta-blockade. Data suggest that patients with
      septic burns already have a maximal metabolic response and that cold stress does
      not further increase this response. Males, ages 17 to 54 years, were found to
      increase their resting energy expenditures by 11.4 kcal/m2/day for each percent
      total body surface area burn. We conclude that beta-blockade with propranolol in
      therapeutic doses may be used in patients with burns without adversely affecting
      the cold stress response.

PMID- 1350284
TI  - Endometriosis 1991: a discussion document.

PMID- 1350285
TI  - Image animation.

PMID- 1350286
TI  - Effect of xamoterol in a patient with idiopathic autonomic failure.
AB  - We report the effect of xamoterol on autonomic, humoral and haemodynamic function
      in a patient with idiopathic autonomic neuropathy. Xamoterol produced marked
      symptomatic improvement, slightly increased heart rates in the sitting, supine
      and upright tilt positions and higher blood pressures while seated and on
      recovery from upright tilt. There were, however, no differences in blood pressure
      responses following a meal or during head-up tilt. We suggest that before
      ascribing symptomatic benefit to xamoterol in this condition, objective
      haemodynamic improvement should be recorded. Further studies of treatment in
      idiopathic autonomic failure require to be placebo controlled.

PMID- 1350287
TI  - Effects of tannic acid on antigenicity and membrane contrast in ultrastructural
      immunocytochemistry.
AB  - We have modified our previous method for immunogold staining of unosmicated,
      plastic-embedded tissue by addition of tannic acid as a post-fixative to increase
      membrane contrast. Overall cell ultrastructure and organelle membranes, in
      particular, appeared well preserved after this treatment. We evaluated
      quantitatively the effect of tannic acid on the antigenicity of several membrane
      proteins in rat liver and intestine. For all antigens tested, significant
      antigenicity was retained on both intracellular and plasma membranes. However,
      the level of antigenicity decreased with increased concentrations of tannic acid.
      This effect was most apparent on the apical and basolateral membranes of
      hepatocytes and on the apical membrane of enterocytes, surfaces that had been in
      direct contact with the tannic acid fixative. The results indicate that when low
      concentrations of tannic acid are employed, this method yields greatly enhanced
      membrane contrast while preserving sufficient antigenicity to facilitate the
      ultrastructural localization of many membrane and other antigens.

PMID- 1350288
TI  - T-deficient transmembrane signaling in CD4+ T cells of retroviral-induced immune
      deficient mice.
AB  - The defective virus found in the LP-BM5 mixture of murine leukemia viruses
      induces a severe immune deficiency disease in C57BL/6 mice that is characterized
      by the activation and expansion of T and B cells that become unresponsive to
      normal immune stimuli. The nature of the biochemical lesion in these defective
      lymphocyte populations remains unknown. Flow cytometric analysis of the T cell
      population in infected animals has demonstrated expansion of both CD4+ and CD8+
      subsets. Despite chronic expansion in vivo, CD4+ T cells by wk 4 postinfection
      failed to up-regulate cell surface IL-2R expression, produced IL-2, or
      proliferate in vitro in response to either Con A, Staphylococcal enterotoxin
      super-antigens, or anti-CD3 stimulation. Exogenous IL-2 did not restore the
      proliferative response and also failed to up-regulate IL-R expression on CD4+ T
      cells from infected mice, even though basal IL-2R expression was initially
      elevated compared to normals. In contrast, CD4+ T cells from infected mice could
      be induced to proliferate by stimulation with PMA and ionomycin resulting in IL
      2R up-regulation, IL-2 production, and proliferation. Moreover, proliferation
      could also be induced by anti-CD3 plus PMA, although anti-CD3 plus ionomycin was
      without effect. These studies suggest that chronic expansion of CD4+ T cells in
      infected mice is probably not maintained by normal TCR signaling, which appears
      defective in these cells. In addition, the lesion in biochemical signaling
      appears to result in defective activation of protein kinase C, which can be
      overcome by direct activation with PMA.

PMID- 1350289
TI  - Glutamate differentially inhibits the expression of class II MHC antigens on
      astrocytes and microglia.
AB  - MHC molecules are required for Ag recognition by T cells. Inasmuch as cells in
      the central nervous system do not express MHC constitutively, appearance of MHC,
      in inflammatory and degenerative diseases of the brain, may indicate local Ag
      presentation and subsequent immune response. Although both astrocytes and
      microglia are capable of class II MHC expression in vitro, in vivo studies failed
      to show the presence of significant amounts of class II on astrocytes compared to
      microglia. Our study is designed to clarify possible regulatory mechanisms that
      can explain the differences in inducibility of class II MHC between astrocytes
      and microglia in vivo. Using dissociated rat brain cell cultures, we have found
      that glutamate, an excitatory neurotransmitter, exerted a profound inhibitory
      effect on IFN-gamma-induced expression of class II on astrocytes, but not on
      microglia. Both glutamate and norepinephrine, a neurotransmitter previously
      reported to down-regulate class II on astrocytes, inhibited the induction of
      class II on astrocytes by eliminating accumulation of class II MHC mRNA. The
      kinetics of class II mRNA induction by IFN-gamma in the presence of glutamate
      suggested that glutamate may act as a transcriptional inhibitor. It is likely
      that class II induction on astrocytes in vivo may be selectively down-regulated
      by neurotransmitters such as glutamate and norepinephrine.

PMID- 1350290
TI  - Cloning and expression of murine IL-12.
AB  - Human IL-12 (NK cell stimulatory factor, cytotoxic lymphocyte maturation factor)
      is a heterodimeric cytokine that can act as a growth factor for activated human T
      and NK cells, enhance the lytic activity of human NK/lymphokine-activated killer
      cells, and stimulate the production of IFN-gamma by resting human PBMC. Because
      in our hands, human IL-12 did not elicit similar responses in murine lymphocytes,
      we have cloned and expressed the murine IL-12 subunit cDNA in order to obtain
      recombinant protein for murine studies. Comparison of the predicted amino acid
      sequences of the murine subunits with their human counterparts revealed that the
      p40 subunits are more highly conserved than the p35 subunits (70% vs 60%
      identity, respectively). The sizes of the p35 and p40 subunit mRNA were estimated
      to be 1.5 kb and 2.6 kb, respectively. RNA blot analysis showed that p35 mRNA was
      expressed in lymphoid tissues (spleen, thymus) and nonlymphoid tissues (lung,
      brain), whereas p40 mRNA expression was only detected in lymphoid cells.
      Incubation of splenocytes with pokeweed mitogen did not significantly affect p35
      mRNA levels, however, it resulted in a decrease of p40 mRNA. Coexpression of the
      murine p35 and p40 cDNA clones in COS cells resulted in the secretion of IL-12,
      which was active in human and mouse T cell proliferation, murine NK cell
      activation, and murine IFN-gamma induction assays. Transfection of each subunit
      cDNA alone did not result in measurable secreted IL-12 activity. A hybrid
      heterodimer consisting of murine p35 and human p40 subunits retained bioactivity
      on murine cells; however, the combination of human p35 and murine p40 was
      completely inactive on murine cells. These results indicate that the observed
      inability of human IL-12 to act on murine cells is largely determined by the p35
      subunit.

PMID- 1350291
TI  - Regulation of tumor necrosis factor production by adrenaline and beta-adrenergic
      agonists.
AB  - The effects of adrenaline and isoproterenol, a specific beta-adrenergic agonist,
      on TNF production were investigated. Both agents inhibited the production of TNF
      by human blood and THP-1 cells stimulated by LPS. The effect of adrenaline was
      prevented by a beta-receptor antagonist, but not by an alpha-receptor antagonist.
      Levels of TNF mRNA were not reduced by adrenaline. Inhibition of TNF production
      was observed only if cells were first exposed to adrenaline or isoproterenol at
      about the same time as to LPS; incubation of THP-1 cells with isoproterenol for
      24 h before LPS stimulation dramatically increased response, and prevented
      suppression of TNF production by a second dose of isoproterenol. Intracellular
      cAMP levels were increased by adrenaline and isoproterenol, at concentrations
      that inhibited TNF production. However, prolonged incubation of THP-1 cells with
      isoproterenol resulted in depression of cAMP concentrations to below basal
      levels. These data suggest that TNF production can be regulated by beta-receptor
      stimulation, that such regulation is mediated by changes in intracellular cAMP
      concentrations and is exerted at a posttranscriptional level. Adrenaline may be
      an important endogenous regulator of TNF production in sepsis.

PMID- 1350292
TI  - Parallel regulation of IL-4 and IL-5 in human helminth infections.
AB  - To investigate the relationship between cytokine production and the increased
      levels of serum IgE and peripheral eosinophilia commonly accompanying human
      helminth infections, we studied the ability of PBMC of normal (N1) (n = 18) and
      eosinophilic individuals with helminth infections (H1) (n = 9) to produce IL-3,
      IL-4, IL-5, granulocyte-macrophage-CSF, and IFN-gamma in vitro after stimulation
      with PMA (50 ng/ml) and ionomycin (1 microgram/ml). The two groups differed in
      both the levels of serum IgE and eosinophilia. For mitogen-induced production of
      granulocyte-macrophage-CSF and IFN-gamma, there was no difference in cytokine
      production between the two groups. In marked contrast, supernatants from PBMC of
      infected individuals had significantly higher levels of IL-4 (mean = 213 pg/ml
      for N1 and 944 pg/ml for H1, p less than 0.02), IL-5 (mean = 180 pg/ml for N1 and
      1118 pg/ml for HL, p less than 0.001), and IL-3 (mean = 13900 pg/ml for N1, 28029
      pg/ml for H1, p less than 0.05). In addition, helminth-infected patients had
      approximately 5-fold greater numbers of T cells capable of producing IL-5 and 2.5
      fold greater frequency of IL-4-secreting cells than did normal individuals; GM
      CSF- and IFN-gamma-producing T cell numbers were not significantly different in
      the two groups. IL-3-producing cell frequencies could not be evaluated by this
      method. There was a direct correlation between IL-4 production and IL-5
      production at the level of both protein production and frequency of T cells
      capable of producing these cytokines. These data indicate that individuals with
      reactive eosinophilia and elevated serum IgE have an expanded population of
      lymphocytes producing IL-4 and IL-5 and the association of the two suggests that
      the regulation of IL-4 and IL-5 may be linked.

PMID- 1350293
TI  - Fibroblast stimulation in schistosomiasis. XII. Identification of CD4+
      lymphocytes within schistosomal egg granulomas as a source of an apparently novel
      fibroblast growth factor (FsF-1).
AB  - Granulomas that form around Schistosoma mansoni eggs deposited in the liver
      secrete a variety of fibrogenic factors that may provide a molecular link between
      chronic inflammation and hepatic fibrogenesis in schistosomiasis. We recently
      isolated from conditioned medium of egg granuloma cultures a approximately equal
      to 60-kDa heparin-binding growth factor for fibroblasts. Because this protein is
      distinct from other defined heparin-binding growth factors, we designated it
      "fibroblast stimulating factor-1" (FsF-1). We now report that FsF-1 is a
      lymphokine. We prepared IgG antibody against purified FsF-1 and determined that
      it did not cross-react with a variety of growth factors or recombinant
      interleukins. Using two-color flow cytometry of dissociated granuloma cell
      suspensions, we observed that approximately 20% to 25% of granuloma CD4+
      lymphocytes express surface FsF-1. We isolated CD4+ granuloma lymphocytes by FACS
      and observed that these cells spontaneously secrete into culture supernatant a
      fibroblast mitogen that is neutralized by anti-FsF-1 antibody. Furthermore, anti
      FsF-1 can specifically immunoprecipitate a metabolically labeled protein produced
      by the granuloma CD4+ lymphocytes. The labeled protein has the same apparent
      molecular mass (approximately equal to 60 kDa) as FsF-1 purified from granuloma
      culture supernatants. These findings define CD4+ lymphocytes as a source of FsF
      1. Because FsF-1 has biologic and chemical features distinct from most other
      defined lymphokines and from other heparin-binding growth factors, FsF-1 appears
      to be a novel lymphokine.

PMID- 1350294
TI  - Structure of the mouse IL-10 gene and chromosomal localization of the mouse and
      human genes.
AB  - The nucleotide sequence of a 7.2-kb segment containing the mouse IL-10 (mIL-10)
      gene was determined. Comparison to the mIL-10 cDNA sequence (Moore, K. W., et al.
      1990. Science 248:1230; 250:494) revealed the presence of five exons that span
      approximately 5.1 kb of genomic DNA. The noncoding regions of the mIL-10 gene
      contain sequences that have been associated with transcriptional regulation of
      several cytokine genes. The mIL-10 gene was mapped to mouse chromosome 1 and the
      human IL-10 gene was also mapped to human chromosome 1.

PMID- 1350295
TI  - Apparent ineffectiveness of natural killer cells vis-a-vis retrovirus-infected
      targets.
AB  - The role of NK cells in the defense against retroviral infections is ill defined.
      The discovery of the pathogenic human retroviruses and their epidemic spread have
      made more urgent a better understanding of how such infections may be naturally
      controlled. Therefore, a systematic study was undertaken to determine whether NK
      cells obtained from healthy individuals are able to recognize and lyse target
      cells that have been infected with HTLV-I, HTLV-II, or HIV. The studies
      demonstrated that NK cells can recognize retrovirus-infected cells as evidenced
      by rapid conjugation, but that neither freshly isolated, nor IL-2 stimulated
      cells cause lysis of such targets. As has been reported for NK-resistant tumor
      cells, removal of sialic acid residues rendered the retrovirus-infected target
      cells vulnerable to NK cell attack. Although these data do not suggest that
      boosting natural immunity would be a useful treatment modality for patients with
      AIDS or HTLV-related diseases, the observations may help to explain why the small
      number of cells that harbor retroviruses in patients with subclinical infection
      are not eliminated.

PMID- 1350296
TI  - Human intercellular adhesion molecule-1 gene and its expression in the skin.
AB  - Cell adhesion molecules are cell-surface proteins that allow specific cell-cell
      interactions among leukocytes, as well as between leukocytes and other cells.
      Recent studies have shown that the differential expression of selected cell
      adhesion molecules plays a critical role in cutaneous inflammation, immunologic
      responses, and wound repair. Intercellular adhesion molecule-1 (ICAM-1) is a cell
      adhesion molecule that is constitutively expressed on human dermal microvascular
      endothelial cells (HDMEC) and is inducible on human keratinocytes (HK). Its
      regulated expression is vital to the initiation and evolution of localized
      inflammatory processes in the skin. ICAM-1 serves as a specific ligand for
      lymphocyte function-associated antigen-1 (LFA-1), a cell-surface protein
      expressed on all leukocytes. The regulated expression of ICAM-1 allows leukocytes
      to bind to endothelial cells at sites of inflammation and, after exiting into the
      tissue, to interact with specific target cells, such as HK. Furthermore, specific
      cytokines are capable of differentially regulating ICAM-1 expression on HDMEC,
      HK, and other cells. The biologic relevance of ICAM-1 expression in cutaneous
      inflammation is further supported by functional studies demonstrating the
      critical role of ICAM-1/LFA-1 interactions in mediating the binding of peripheral
      blood leukocytes to HDMEC and to HK--cells known to be participants and targets
      in specific cutaneous immunologic responses. Thus, the delineation of precise
      molecular mechanisms that regulate the tissue-specific and cytokine-specific
      expression if ICAM-1 is important to both our understanding of the biology of
      localized inflammation and to the development of directed anti-inflammatory
      therapeutic strategies. Current evidence indicates that ICAM-1 expression is
      regulated at the level of gene transcription. Recently our laboratory has
      isolated and characterized a human genomic clone that contains the 5' regulatory
      region of the ICAM-1 gene. In the current studies, we further describe the
      genomic ICAM-1 clones isolated to date and demonstrate the presence of consensus
      regulatory elements located within the 5' flanking region of the ICAM-1 gene that
      are potentially involved in regulating ICAM-1 gene transcription.

PMID- 1350297
TI  - Comparison of hemagglutinating pili of type b and nontypeable Haemophilus
      influenzae.

PMID- 1350298
TI  - Comparison of the alpha-pilins of Haemophilus influenzae type b strains Eagan
      (p+), M43 (p+), and 770235bof+.

PMID- 1350299
TI  - Capsule loss by Haemophilus influenzae type b results in enhanced adherence to
      and entry into human cells.

PMID- 1350300
TI  - Expression of pili by Haemophilus ducreyi.

PMID- 1350301
TI  - Fimbria-mediated adherence and hemagglutination of Haemophilus influenzae.
AB  - The gram-negative bacterium Haemophilus influenzae expresses morphologically and
      functionally distinct types of fimbriae, of which the LKP fimbriae mediate
      hemagglutination and adherence to human epithelial cells but hamper mucosal
      invasion. Therefore, the both in vivo and in vitro observed fimbrial phase
      variation may contribute to the pathogenesis of the infection. The existence of
      greater than 14 LKP serotypes hampers vaccine development based on fimbriae,
      since a monovalent fimbria vaccine confers protection against only the homologous
      strain. Cloning of the fimbrial genes in Escherichia coli results in the
      expression of morphologically intact fimbriae. Analysis of the cloned DNA
      indicates that a fimbrial gene cluster is necessary for formation of complete
      fimbriae and for fimbria-mediated adherence. The gene encoding the subunit is
      highly conserved among H. influenzae and belongs to the family of E. coli
      fimbriae. The phase variation is transcriptionally regulated by variation of the
      length of the reiterated sequence that forms the promoter region of the subunit
      gene.

PMID- 1350302
TI  - A variable number of tandem repeats locus within the human complement C2 gene is
      associated with a retroposon derived from a human endogenous retrovirus.
AB  - We have previously described multiallelic restriction fragment length
      polymorphisms of the C2 gene, suggesting the presence of a variable number of
      tandem repeats (VNTR) locus. We report here the cloning and sequencing of the
      polymorphic fragments from the two most common alleles of the gene, a and b. The
      results confirm the presence of a VNTR locus consisting of a nucleotide sequence,
      41 bp in average length, repeated tandemly 23 and 17 times in alleles a and b,
      respectively. The difference in the number of repeats between the two alleles is
      due to the deletion/insertion of two noncontiguous segments, 143 and 118 bp long,
      of allele a, and of a 40-bp segment of allele b. The VNTR region is associated
      with a SINE (short interspersed sequence)-type retroposon, SINE-R.C2, located
      within the third intron of the C2 gene. SINE-R.C2 is a member of a previously
      described large retroposon family of the human genome, apparently derived from
      the human endogenous retrovirus, (HERV) K10, which is homologous to the mouse
      mammary tumor virus.

PMID- 1350304
TI  - The present status of akathisia.

PMID- 1350303
TI  - Tumour necrosis factor and interleukin 6 production during interaction between
      activated CD4+ lymphocytes and simian immunodeficiency virus-infected
      macrophages.
AB  - The mechanism for the gradual loss of CD4+ T lymphocytes and the development of
      the slowly progressive inflammatory/degenerative lesions that accompany human
      immunodeficiency virus infection are poorly understood. Using the Simian
      immunodeficiency virus (SIVmac) macaque model of AIDS, we found that persistently
      infected primary macrophages fuse with primary activated CD4+ lymphocytes and
      that this interaction results in production of tumour necrosis factor-alpha (TNF
      alpha) and interleukin 6 (IL-6). An earlier report had shown that SIV-infected
      macaque macrophages fuse with CEM174 cells (a human CD4+ cell line) and cause
      their lysis. In the present report, we have shown that TNF-alpha and IL-6 are
      also produced during the early stages of this interaction. Data from
      cocultivation of infected macrophages with several CD4+ T cell lines, including
      CEM174, suggested that the cytokines are produced by the T cells, and that
      cytokine production is restricted to those cells which not only express CD4, but
      are also capable of fusing with the infected macrophages. These data suggest that
      infected macrophages in vivo could fuse with and eliminate activated CD4+
      lymphocytes and, during this interaction, release cytokines, which would
      contribute to the degenerative and inflammatory lesions characteristic of this
      disease.

PMID- 1350305
TI  - Potentiation of mossy fiber-evoked EPSPs in turtle cerebellar Purkinje cells by
      the metabotropic glutamate receptor agonist 1S,3R-ACPD.
AB  - 1. The effects of the metabotropic glutamate receptor (mGluR) agonist 1S,3R-ACPD
      on excitatory postsynaptic potentials (EPSPs) evoked by stimulation of mossy
      fibers (MF) and parallel fibers (PF) were examined in turtle cerebellar Purkinje
      cells. 2. 1S,3R-ACPD (1-25 microM) reversibly potentiated the amplitude of the MF
      evoked EPSPs and revealed a late, slow EPSP component, but was without effect on
      PF-evoked EPSPs. The potentiation of both components of MF-evoked EPSPs was dose
      dependent, with an ED50 of approximately 3 microM. At higher doses (15-25 microM)
      1S,3R-ACPD produced a direct depolarization of Purkinje cells in 57% of cells
      examined. 3. The enhancement of MF EPSPs by 1S,3R-ACPD was blocked by the N
      methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate (AP
      5), but not by the mGluR antagonist L-2-amino-3-phosphonopionic acid (L-AP3; 1
      mM), or the 1R,3S isomer of ACPD (25-500 microM). 4. The results demonstrate that
      mGluR activation by 1S,3R-ACPD produces a potent, stereospecific facilitation of
      NMDA receptor-mediated transmission at the MF-granule cell synapse.

PMID- 1350306
TI  - Isolated NMDA receptor-mediated synaptic responses express both LTP and LTD.
AB  - 1. The possibility of use-dependent, long-lasting modifications of
      pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated synaptic
      transmission was examined by intracellular recordings from granule cells of the
      hippocampal dentate gyrus in vitro. In the presence of the non-NMDA receptor
      antagonist 6-cyano-7-nitroquinaxaline-2,3-dione (CNQX, 10 microM) robust, long
      term potentiation (LTP) of NMDA receptor-mediated synaptic potentials was induced
      by brief, high (50 Hz) and lower (10 Hz) frequency tetanic stimuli of
      glutamatergic afferents (60 +/- 6%, n = 8, P less than 0.001 and 43 +/- 12%, n =
      3, P less than 0.05, respectively). 2. Hyperpolarization of granule cell membrane
      potential to -100 mV during 50-Hz tetanic stimuli reversibly blocked the
      induction of LTP (-6 +/- 2%, n = 6, P greater than 0.05) indicating that
      simultaneous activation of pre- and postsynaptic elements is a prerequisite for
      potentiation of NMDA receptor-mediated synaptic transmission. In contrast,
      hyperpolarization of the granule cell membrane potential to -100 mV during 10-Hz
      tetanic stimuli resulted in long-term depression (LTD) of NMDA receptor-mediated
      synaptic potentials (-34 +/- 8%, n = 8, P less than 0.01). 3. We also studied the
      role of [Ca2+]i in the induction of LTP and LTD of NMDA receptor-mediated
      synaptic responses. Before tetanization, [Ca2+]i was buffered by iontophoretic
      injections of bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA). BAPTA
      completely blocked the induction of LTP (3 +/- 5%, n = 13) and partially blocked
      LTD (-14.8 +/- 6%, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350307
TI  - Modulation of cortical evoked potentials by stimulation of nucleus raphe magnus
      in rats.
AB  - 1. In pentobarbital sodium-anesthetized rats, we evaluated changes in cortical
      evoked potentials (EPs) associated with electrical and chemical stimulation of
      nucleus raphe magnus (NRM). A condition-test (C-T) paradigm was used. Cortical
      EPs were produced by test stimuli delivered to a hindpaw or the thalamic ventral
      posterior lateral nucleus (VPL; electrical stimulation), or by photic stimulation
      of the eyes or electrical stimulation of contralateral homotopical cortex
      (transcallosal EPs). These test stimuli were then preceded by electrical or
      chemical conditioning stimulation (CS) delivered to NRM through a stereotaxically
      implanted electrode or injection cannula, respectively. Effects of CS on EPs
      produced by the test stimuli were characterized. 2. Electrical CS preceding a
      test stimulus delivered to the foot reduced the amplitude of EPs at thresholds as
      low as 10-25 microA. The magnitude of EP reduction was dependent on CS intensity,
      frequency, and the C-T interval. Optimal parameters were trains of 10 pulses (400
      Hz) delivered at a C-T interval of 5-10 ms. Injection of glutamate and lidocaine
      into NRM demonstrated that these effects were due to activation of NRM neurons
      and not to current spread to medial lemniscus (ML). NRM CS also reduced cortical
      EPs produced by test stimulation in VPL but did not alter EPs from visual
      stimulation or from electrical stimulation of contralateral homotopical cortex.
      3. These findings suggest that NRM CS attenuates EPs by inhibiting thalamic or
      thalamocortical afferent activity. Because NRM CS affected all components of the
      cortical EPs, the effect appears to involve alteration of general sensory
      activity and is not nociception specific.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350308
TI  - Long-term potentiation in slices of kitten visual cortex and the effects of NMDA
      receptor blockade.
AB  - 1. A slice preparation was used to study layer III field potentials (FPs) evoked
      by electrical stimulation of the white matter-layer VI border and their
      potentiation by patterned stimuli. 2. The dependence of the FP on recording
      position was investigated. The maximum field was recorded in layer III at a
      position radial to the site of stimulation. Because this negative FP reflects an
      excitatory synaptic current sink, this site was chosen for all subsequent
      experiments. 3. Under normal recording conditions, components of the layer III FP
      with latencies greater than 3 ms were completely abolished by kynurenate but
      unaffected by 2-amino-5-phosphonovalerate (AP5), indicating that this potential
      reflects the activation of non-NMDA excitatory amino acid receptors. 4. Addition
      of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline methiodide
      (BMI) broadened the field potential and revealed an AP5-sensitive component. By
      filling the recording pipette with BMI, it was possible to substantially reduce
      inhibition locally around the recording site while avoiding stimulus-driven and
      spontaneous epileptiform activity. 5. Tetanic stimulation elicited a long-term
      potentiation (LTP) of the FP in 14 of 17 experiments when the BMI-filled pipette
      method was used. 6. Addition of 100 microM D,L-AP5 significantly reduced the
      average probability and magnitude of LTP. Nonetheless, in 2 of 8 experiments,
      significant LTP was observed after a tetanus in the presence of AP5. Control
      experiments confirmed that this concentration of AP5 was sufficient to maximally
      block cortical NMDA receptors. 7. We conclude that LTP of layer III field
      potentials can be reliably elicited, provided that GABAA-receptor mediated
      inhibition is blocked locally at the site of recording and that NMDA receptors
      are recruited during the conditioning stimulation. However, activation of NMDA
      receptors is apparently not an obligatory step for the induction of use-dependent
      increases in synaptic strength in the kitten striate cortex.

PMID- 1350309
TI  - Selective beta 3-adrenergic agonists of brown adipose tissue and thermogenesis.
      1. [4-[2-[(2-Hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetates.
AB  - The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate
      (8) has been identified as the most interesting member of a series of selective
      beta 3-adrenergic agonists of brown adipose tissue and thermogenesis in the rat.
      In vivo it acts mainly via the related acid 10. Potency was generally markedly
      reduced by placing substituents on the phenyl ring of the phenoxypropanolamine
      unit of 8; only the 2-fluoro analogue 16 had comparable potency to 8. Other
      structure-activity relationships are discussed. Further testing of 8 (ICI 198157)
      has shown that in the rat it stimulates the beta 3-adrenergic receptor in brown
      adipose tissue at doses lower than those at which it affects beta 1 and beta 2
      adrenergic receptors in other tissues. It increases metabolic rate, as judged by
      an increase in oxygen consumption, and in the genetically obese Zucker rat it
      causes a reduced rate of weight gain. This class of compound may be useful in the
      treatment of obesity in man.

PMID- 1350310
TI  - Selective beta 3-adrenergic agonists of brown adipose tissue and thermogenesis.
      2. [4-[2-[(2-Hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetamides.
AB  - The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate
      (1) (R1 = OMe) had previously been identified as the most interesting member of a
      series of selective beta 3-adrenergic agonists of brown adipose tissue and
      thermogenesis in the rat. In vivo it acts mainly via the related acid 1 (R1 =
      OH). Amides have been examined to determine whether they have advantages over the
      ester. In particular, in the rat and dog the half-lives of amides of appropriate
      potency were no longer than those of the ester. The amide (S)-4-[2-[(2-hydroxy-3
      phenoxypropyl)amino]ethoxy]-N-(2- methoxyethyl)phenoxyacetamide [S-27, ICI D7114]
      was selected as having properties consistent with a sustained-release formulation
      should that prove necessary. Unlike the ester it is resistant to hydrolysis in
      the gut lumen. Further testing of ICI D7114 has shown that in the rat, cat, and
      dog it stimulates the beta 3-adrenergic receptor in brown adipose tissue at doses
      lower than those at which it affects beta 1- and beta 2-adrenergic receptors in
      other tissues. Slimming effects were observed in the dog. ICI D7114 may be a
      selective thermogenic agent in man and may be useful in the treatment of obesity
      and diabetes.

PMID- 1350311
TI  - Central nervous system trauma status report, 1991. 7th Conference on Neural
      Trauma, Virginia, September 23-26, 1990 and 8th Annual Neurotrauma Symposium, St.
      Louis, October 27-29, 1990.

PMID- 1350312
TI  - Neurotransmitter-mediated mechanisms of traumatic brain injury: acetylcholine and
      excitatory amino acids.
AB  - Research into traumatic brain injury (TBI), focusing on changes in energy
      metabolism, cerebrovascular dysfunction, and brain parenchymal morphology, has
      not produced complete descriptions of mechanisms mediating the pathophysiology of
      TBI. New studies indicate that neurochemical alterations mediate important
      components of brain physiology associated with TBI, and these alterations may be
      responsive to pharmacologic therapy. We discuss rodent models of TBI, review
      current experimental evidence of muscarinic cholinergic and excitatory amino acid
      (EAA) receptor involvement in its pathophysiology, and address issues relevant to
      the interpretation of these data.

PMID- 1350314
TI  - Second World Congress on Science and Football. Eindhoven, The Netherlands, 22-25
      May 1991. Abstracts.

PMID- 1350313
TI  - Adaptive regulation in skeletal muscle glutamine metabolism in endotoxin-treated
      rats.
AB  - The effects of a single dose of endotoxin (7.5 mg/kg BW) on skeletal muscle
      glutamine metabolism were studied in vivo in rats to gain further understanding
      of the altered glutamine metabolism that characterizes sepsis and other catabolic
      diseases. In endotoxin-treated animals the arterial glutamine concentration fell
      early initially and then increased compared with control values. Twelve hours
      after treatment, the arteriovenous concentration difference for glutamine across
      the hindquarter doubled, resulting in a significant increase in net muscle
      glutamine release in endotoxin-treated rats. As a consequence, the muscle
      glutamine concentration fell in the endotoxin-treated animals by 25%-40%, an
      event that was apparent as early as two hours after endotoxin treatment. Skeletal
      muscle glutaminase activity, the major enzyme of glutamine breakdown, was
      unchanged by endotoxemia, but expression of glutamine synthetase mRNA and
      glutamine synthetase specific activity increased in a time-dependent fashion. The
      glutamine depletion that develops in skeletal muscle during endotoxemia is caused
      by accelerated muscle glutamine release rather than an increase in intracellular
      degradation or a fall in intracellular biosynthesis. The adaptive increase in
      glutamine synthetase expression that occurs requires de novo RNA and protein
      synthesis and may be designed to prevent complete depletion of the intracellular
      glutamine pool.

PMID- 1350315
TI  - Isolation and characterization of the major vegetative RNA polymerase of
      Streptomyces coelicolor A3(2); renaturation of a sigma subunit using GroEL.
AB  - The promoter region of the agarase gene (dagA) of Streptomyces coelicolor A3(2)
      is complex; it consists of four distinct promoters with different -10 and -35
      regions. We report the isolation of a form of RNA polymerase that mediates
      transcription in vitro from the dagAp4 promoter. The core components of this RNA
      polymerase are associated with a polypeptide of c. 66 kDa; holoenzyme
      reconstitution experiments show that the 66 kDa polypeptide functions as a sigma
      factor that directs transcription from the dagAp4 and Bacillus subtilis veg
      promoters in vitro. Alignment of the DNA sequences of these two promoters shows
      that they have bases in common in the -10 and -35 regions and that these
      sequences are similar to those observed for the major RNA polymerases of other
      bacteria. N-terminal amino acid sequence analysis of the 66 kDa polypeptide
      revealed it to be the product of the hrdB gene. Previous experiments showed that
      the predicted amino acid sequence of the hrdB gene product is very similar to the
      major sigma factors of other bacteria and suggested that disruption of the hrdB
      gene is lethal. These observations together lead to the conclusion that we have
      isolated the major RNA polymerase of Streptomyces coelicolor A3(2). We have
      developed an improved protocol for the renaturation of sigma factors that have
      been isolated by preparative sodium dodecyl sulphate/polyacrylamide gel
      electrophoresis (SDS-PAGE). This method involves renaturing the polypeptide in
      the presence of the bacterial chaperonin GroEL. We expect this protocol to find
      general application for renaturation of other polypeptides that have been
      subjected to SDS-PAGE.

PMID- 1350316
TI  - High-frequency rearrangements in the chromosome of Mycoplasma pulmonis correlate
      with phenotypic switching.
AB  - Mycoplasma pulmonis is a murine pathogen that causes chronic respiratory disease
      in laboratory rats and mice. Several examples of high-frequency phenotypic
      switching have been reported for M. pulmonis, the molecular basis of which is
      unknown. We report here that during growth the M. pulmonis chromosome undergoes
      DNA rearrangements at a high frequency. Some of the rearrangements we examined
      correlated with changes in the susceptibility of the cells to mycoplasma virus
      P1, an example of phenotypic switching involving changes in surface antigen
      structure. Other rearrangements, unrelated to phenotypic switching, involved a
      DNA element present in the chromosome in multiple copies. The high level of DNA
      recombination that occurred in M. pulmonis indicates that this may be one of the
      most variable genomes studied to date. High levels of DNA recombination may
      contribute to the unusually high rate of evolution that mycoplasmas are thought
      to be undergoing. Understanding the molecular basis for this phenomenon may
      provide an insight into the chronic nature of many mycoplasmal infections.

PMID- 1350317
TI  - Effects of adrenergic blockers on central nervous system-mediated hyperglycemia
      in fed rats.
AB  - We studied the effect of adrenergic blockade on hepatic venous hyperglycemia and
      the activation of a hepatic glycogenolytic enzyme, phosphorylase-a, in response
      to cerebral cholinergic activation. Neostigmine was injected into the third
      cerebral ventricle of bilaterally adrenodemedullectomized (ADMX) rats, while
      somatostatin and insulin were administered intravenously. Hepatic venous plasma
      glucose concentrations and hepatic phosphorylase-a activity were measured.
      Intracerebroventricular injection of neostigmine (5 x 10(-8) mol) caused
      increases in hepatic venous glucose concentrations and hepatic phosphorylase-a
      activity. Both of these changes were prevented by intraperitoneal (IB)
      pretreatment with phentolamine (5 x 10(-7), 1 x 10(-6) mol) without the
      intervention of insulin secretion, but not by pretreatment with the alpha
      adrenoreceptor antagonist phenoxybenzamine (1 x 10(-6) mol), the beta
      adrenoreceptor antagonist propranolol (1 x 10(-6) mol), the alpha 1-antagonists
      prazosin or bunazosin (1 x 10(-6) mol), the alpha 2-antagonist yohimbine (1 x 10(
      6) mol), or prazosin (5 x 10(-7) mol) plus yohimbine (5 x 10(-7) mol). These
      results suggest that phentolamine prevented brain-mediated hepatic glycogenolysis
      by a mechanism that may not be classified pharmacologically as involving either
      alpha 1- or alpha 2-receptors.

PMID- 1350318
TI  - Drug overdose--reducing the load.
AB  - OBJECTIVE: To review available information about various methods for reducing
      gastrointestinal absorption of a poison or drug. DATA SOURCES: Articles on
      overdose and accidental poisoning generated by the Australian Medlars Service and
      concentrating on the period between 1985 and 1990 were surveyed. Earlier studies
      were included if relevant. STUDY SELECTION AND DATA EXTRACTION: English language
      articles with an emphasis on studies using objective methods to measure
      individual and comparative efficacy of gastrointestinal decontamination
      techniques were selected. A total of 65 articles were reviewed. DATA SYNTHESIS:
      Gastric emptying procedures (gastric lavage or emesis caused by syrup of ipecac)
      are only effective if performed within one hour of drug ingestion. Gastric lavage
      is superior to syrup of ipecac. Oral administration of activated charcoal is more
      effective than either gastric emptying procedure, and is recommended for most
      cases of poisoning. Cathartics (sorbitol) can be used with activated charcoal.
      Whole bowel lavage with polyethylene glycol is indicated in selected cases of
      potentially lethal overdose where the toxic substance cannot be absorbed by
      charcoal and has passed the pylorus. CONCLUSIONS: Children--syrup of ipecac can
      be given at home to children older than 12 months. Most children who reach
      hospital can be treated by charcoal alone. ADULTS--Most patients are managed with
      supportive care and, in the absence of contraindications, a single dose of
      activated charcoal if seen within four hours of ingestion of the poison or drug.
      Gastric lavage is used if the patient presents within one hour of ingestion and
      has clinical features of toxicity.

PMID- 1350319
TI  - Guidelines for the performance of CD4+ T-cell determinations in persons with
      human immunodeficiency virus infection.
AB  - This document has been developed by CDC to give guidance to laboratories
      performing lymphocyte immunophenotyping assays in human immunodeficiency virus
      infected persons. The recommendations in this document reflect current technology
      in a field that is rapidly changing. The recommendations apply to laboratory
      safety, specimen collection, specimen transport, maintenance of specimen
      integrity, specimen processing, flow cytometer quality control, sample analyses,
      data analysis, data storage, data reporting, and quality assurance.

PMID- 1350320
TI  - Chronic selegiline administration transiently decreases tyrosine hydroxylase
      activity and mRNA in the rat nigrostriatal pathway.
AB  - Selegiline, a selective monoamine oxidase type B inhibitor, is beneficial in the
      treatment of Parkinson's disease. However, this beneficial effect is only
      transient, and patients must ultimately resort to treatment with standard
      levodopa therapy. We studied the effects of chronic selegiline treatment on the
      rat nigrostriatal pathway, to elucidate a neurochemical correlate for this
      adaptive clinical response. Selegiline treatment for 3, 7, 14, or 21 days
      decreased tyrosine hydroxylase (the enzyme that catalyzes the rate-limiting step
      in catecholamine biosynthesis) activity in the cell body regions (substantia
      nigra) of the nigrostriatal pathway. However, tyrosine hydroxylase activity
      measurements in the major terminal field region (corpus striatum) of the pathway
      did not correspond to those in the substantia nigra; in the corpus striatum,
      tyrosine hydroxylase activity was decreased at 3 and 7 days of treatment and
      recovered by 14 days. We tested whether the decrease in tyrosine hydroxylase
      activity was mediated by a decrease in tyrosine hydroxylase mRNA. Northern blot
      and RNA dot blot analyses (using a tyrosine hydroxylase-specific cDNA probe) of
      substantia nigra homogenates revealed a significant decrease in tyrosine
      hydroxylase mRNA at 3, 7, and 14 days of selegiline treatment, compared with
      controls. Conversely, after 21 days of selegiline, tyrosine hydroxylase mRNA
      levels were significantly higher (3-fold) than controls; this finding was not
      reflected in substantia nigra tyrosine hydroxylase activity. The 21-day increase
      in mRNA may be associated with the rebound in tyrosine hydroxylase activity
      observed in the corpus striatum. Thus, it is possible that the recovery in
      tyrosine hydroxylase activity in the corpus striatum is mediated through an
      increase in tyrosine hydroxylase protein transport from the substantia nigra to
      the corpus striatum and/or that the tyrosine hydroxylase enzyme exists in a more
      stabilized state during this period of time. These results demonstrate that
      monoamine oxidase type B-selective inhibitory doses of selegiline are capable of
      inducing transient decreases in tyrosine hydroxylase activity and tyrosine
      hydroxylase mRNA levels. Furthermore, these reversible effects may represent
      adaptive responses associated with pharmacological tolerance and the transient
      beneficial actions of this drug in Parkinson's disease.

PMID- 1350321
TI  - Beta 1- and beta 2-adrenergic receptors display subtype-selective coupling to Gs.
AB  - beta-Adrenergic receptor (beta AR) subtypes differ in their affinities for some
      agonists and antagonists and thus may potentially impart different cellular
      effects based on this ligand-binding specificity. However, the possibility that
      there may be subtype-specific events subsequent to ligand binding has not been
      evaluated extensively. In particular, although beta ARs stimulate adenylyl
      cyclase by coupling to the guanine nucleotide-binding protein Gs, no studies have
      directly assessed the coupling efficiencies among isolated beta AR subtypes. We,
      therefore, permanently transfected the mammalian fibroblast cell line CHW-1102
      with beta 1- or beta 2AR cDNAs and studied the coupling characteristics of these
      two receptor subtypes, each expressed at approximately 335 fmol/mg of protein.
      Both receptors mediated equivalent maximal increases in adenylyl cyclase
      activities (6.63 +/- 1.85-fold for beta 1AR versus 6.10 +/- 0.53-fold for beta
      2AR; p = not significant). However, the isoproterenol dose-response curves for
      the beta 2AR were shifted to the left, compared with those for the beta 1AR (EC50
      of 52.3 +/- 2.87 nM and 191 +/- 10.5 nM, respectively; p less than 0.05),
      resulting in an approximately 4-fold greater potency for the beta 2AR versus the
      beta 1AR. Thus, at the submaximal isoproterenol concentration of 30 nM, the beta
      2AR stimulated adenylyl cyclase approximately 50% more than did the beta 1AR.
      This finding was not due to a difference in the affinities of isoproterenol for
      these receptors, which were found to be the same, as determined by competition
      binding studies with 125I-cyanopindolol in the presence of GTP. The ability of
      beta 1- and beta 2ARs to form the high affinity ternary complex was assessed in
      agonist competition studies without guanine nucleotide. We found that, whereas
      the proportion of receptors in the high affinity state was equivalent between the
      two receptor subtypes, the affinity of this state for isoproterenol was
      approximately 5-fold greater for the beta 2AR, compared with the beta 1AR (KH for
      beta 2AR, 11.8 +/- 3.1 nM; KH for beta 1AR, 61.7 +/- 18.3 nM; p less than 0.05).
      In addition, we examined physical and functional coupling of beta 1- and beta
      2ARs to Gs using the agonist epinephrine, which also has equal binding affinity
      for both receptor subtypes. As with isoproterenol, epinephrine was more potent in
      stimulating adenylyl cyclase and promoted a higher affinity ternary complex for
      the beta 2AR. Thus, a greater degree of both physical and functional agonist
      promoted coupling occurs between Gs and beta 2AR, compared with beta 1AR. We
      conclude that coupling to Gs by beta 1- and beta 2ARs is subtype selective and is
      a potentially important distinguishing feature among these members of the beta AR
      family.

PMID- 1350322
TI  - Conservation of the kinaselike regulatory domain is essential for activation of
      the natriuretic peptide receptor guanylyl cyclases.
AB  - The natriuretic peptide receptors, NPR-A and NPR-B, are two members of the newly
      described class of receptor guanylyl cyclases. The kinaselike domain of these
      proteins is an important regulator of the guanylyl cyclase activity. To begin to
      understand the molecular nature of this type of regulation, we made complete and
      partial deletions of the kinase domain in NPR-A and NPR-B. We also made chimeric
      proteins in which the kinase domains of NPR-A and NPR-B were exchanged or
      replaced with kinase domains from structurally similar proteins. Complete
      deletion of the kinase homology domain in NPR-A and NPR-B resulted in
      constitutive activation of the guanylyl cyclase. Various partial deletions of
      this region produced proteins that had no ability to activate the enzyme with or
      without hormone stimulation. The kinase homology domain can be exchanged between
      the two subtypes with no effect on regulation. However, structurally similar
      kinaselike domains, such as from the epidermal growth factor receptor or from the
      heat-stable enterotoxin receptor, another member of the receptor guanylyl cyclase
      family, were not able to regulate the guanylyl cyclase activity correctly. These
      findings suggest that the kinaselike domain of NPR-A and NPR-B requires strict
      sequence conservation to maintain proper regulation of their guanylyl cyclase
      activity.

PMID- 1350323
TI  - X rays induce interallelic homologous recombination at the human thymidine kinase
      gene.
AB  - We have developed a human lymphoblast cell line for the study of interchromosomal
      homologous recombination at the endogenous thymidine kinase (tk) gene on
      chromosome 17 (M. B. Benjamin, H. Potter, D. W. Yandell, and J. B. Little, Proc.
      Natl. Acad. Sci. USA 88:6652-6656, 1991). This cell line (designated 6:86)
      carries unique heterozygous frameshift mutations in exons 4 and 7 of its
      endogenous tk alleles and can revert to TK+ by frame-restoring mutations, gene
      conversion, or reciprocal recombination. Line 6:86 reverts spontaneously to TK+
      at a frequency of 10(-7) to 10(-8), and exposures to X-irradiation or the
      frameshift mutagen ICR-191 induce increased reversion frequencies in a dose
      dependent manner. Another cell line (designated 4:2) carries a homozygous exon 7
      frameshift and is not expected to revert through mechanisms other than frame
      restoring mutation. Line 4:2 reverts to TK+ at a lower spontaneous frequency than
      does 6:86 but can be induced with similar kinetics by ICR-191. In contrast to
      line 6:86, however, X rays did not induce detectable reversion of line 4:2. We
      have characterized a number of 6:86-derived revertants by means of restriction
      fragment length polymorphism analysis at tk and linked loci, single-strand
      conformation polymorphisms, and direct transcript sequencing. For X rays, most
      revertants retain both original mutations in the genomic DNA, and a subset of
      these frameshift-retaining revertants produce frameshift-free message, indicating
      that reversion is the result of reciprocal recombination within the tk gene.
      Frame-restoring point mutations, restoration of original sequences, and phenocopy
      reversion by acquisition of aminopterin resistance were also found among X-ray
      induced revertants, whereas the ICR-191-induced revertants examined show only
      loss of the exon 7 frameshift.

PMID- 1350324
TI  - Negative autoregulation of the neu gene is mediated by a novel enhancer.
AB  - In an attempt to study potential feedback regulation of the neu oncogene, we have
      found that the neu oncogene product specifically represses its own promoter
      activity. Deletion analysis indicated a 140-bp region (nucleotides -312 to -173
      relative to the ATG initiation codon) in the rat neu promoter responsible for neu
      autorepression. Gel shift assays and methylation interference analysis further
      demonstrated that a GGTGGGGGGG sequence (nucleotides -243 to -234 relative to the
      ATG initiation codon) in this 140-bp region interacts with specific protein
      complexes. The GGTGGGGGGG sequence (GTG element), which functions as an enhancer,
      is sufficient to cause neu-mediated repression in a heterologous promoter.
      Furthermore, it produces different gel shift patterns with nuclear extracts from
      neu-transformed cell lines and their parental lines, suggesting that a
      transcriptional factor(s) interacting with this enhancer element has been
      perturbed by the introduction of neu. Taken together, the data presented in this
      report show that (i) the neu oncogene product autorepresses its own promoter,
      (ii) the neu promoter contains a novel enhancer, and (iii) neu autorepression is
      mediated through this enhancer, likely by inhibition of the enhancer activity.

PMID- 1350325
TI  - Multidrug resistance in Leishmania donovani is conferred by amplification of a
      gene homologous to the mammalian mdr1 gene.
AB  - Drug resistance is a major impediment to the effective treatment of parasitic
      diseases. The role of multidrug resistance (mdr) genes and their products in this
      drug resistance phenomenon, however, remains controversial. In order to determine
      whether mdr gene amplification and overexpression can be connected to a multidrug
      resistance phenotype in parasitic protozoa, a mutant strain of Leishmania
      donovani was generated by virtue of its ability to proliferate in medium
      containing increasing concentrations of vinblastine. The vinblastine-resistant
      strain, VINB1000, displayed a cross-resistance to puromycin and the
      anthracyclines, a growth phenotype that could be attributed to an impaired
      ability to accumulate the toxic drugs. By using the polymerase chain reaction,
      two different DNA fragments, LEMDR06 and LEMDRF2, were amplified from leishmanial
      genomic DNA, and each amplified fragment encoded a product that was significantly
      homologous to parts of the mammalian P-glycoprotein. In the VINB1000 strain, the
      mdr gene recognized by the LEMDR06 probe was amplified approximately 50-fold in
      copy number, whereas the mdr genes that hybridized to LEMDRF2 or to a fragment of
      the previously characterized ltpgpA gene were not amplified. Moreover, the
      VINB1000 cell line expressed a LEMDR06 gene transcript of 12.5 kb in size that
      was not detected in the parental wild-type strain. To furnish a functional test
      for mdr gene amplification and expression in L. donovani, the L. donovani gene
      recognized by the LEMDR06 polymerase chain reaction product, ldmdr1, was isolated
      from a genomic library, transfected into wild-type cells, and amplified over 500
      fold by selection in 0.5 mg of G418 per ml. The resulting transfectants were
      resistant to all drugs to which VINB1000 cells were resistant and sensitive to
      all drugs to which VINB1000 cells were sensitive. These studies demonstrate that
      amplification of the ldmdr1 gene either by direct selection or subsequent to
      transfection can confer a drug-resistant phenotype in parasitic protozoa similar
      to that observed for MDR mammalian cells.

PMID- 1350326
TI  - Effect of polymorphism of an MHC-linked transporter on the peptides assembled in
      a class I molecule.
AB  - Short antigenic peptides bound in the groove of class I major histocompatibility
      complex molecules enable T cells to detect intracellular pathogens. It has been
      assumed that structural features of the class I molecule alone select which
      peptides are bound. It is now demonstrated that a complex polymorphism in one of
      the major histocompatibility complex-encoded putative peptide-transporter genes
      is associated with an altered spectrum of bound peptides.

PMID- 1350327
TI  - The spread of Na+ spikes determines the pattern of dendritic Ca2+ entry into
      hippocampal neurons.
AB  - The dendrites of many types of neurons contain voltage-dependent Na+ and Ca2+
      conductances that generate action potentials (see ref. 1 for review). The
      function of these spikes is not well understood, but the Ca2+ entry stimulated by
      spikes probably affects Ca(2+)-dependent processes in dendrites. These include
      synaptic plasticity, cytotoxicity and exocytosis. Several lines of evidence
      suggest that dendritic spikes occur within subregions of the dendrites. To study
      the mechanism that govern the spread of spikes in the dendrites of hippocampal
      pyramidal cells, we imaged Ca2+ entry with Fura-2 (ref. 9) and Na+ entry with a
      newly developed Na(+)-sensitive dye. Our results indicate that Ca2+ entry into
      dendrites is triggered by Na+ spikes that actively invade the dendrites. The
      restricted spatial distribution of Ca2+ entry seems to depend on the spread of
      Na+ spikes in the dendrites, rather than on a limited distribution of Ca2+
      channels. In addition, we have observed an activity-dependent process that
      modulates the invasion of spikes into the dendrites and progressively restricts
      Ca2+ entry to more proximal dendritic regions.

PMID- 1350328
TI  - Changing role of even-skipped during the evolution of insect pattern formation.
AB  - The development of Drosophila is typical of the so-called long germband mode of
      insect development, in which the pattern of segments is established by the end of
      the blastoderm stage. Short germband insects, such as the grasshopper
      Schistocerca americana, by contrast, generate all or most of their metameric
      pattern after the blastoderm stage by the sequential addition of segments during
      caudal elongation. This difference is discernible at the molecular level in the
      pattern of initiation of the segment polarity gene engrailed, and the homeotic
      gene abdominal-A (ref. 5). For example, in both types of insects, engrailed is
      expressed by the highly conserved germband stage in a pattern of regularly spaced
      stripes, one stripe per segment. In Drosophila, the complete pattern is visible
      by the end of the blastoderm stage, although engrailed appears initially in
      alternate segments in a pair-rule pattern that reflects its known control by pair
      rule genes such as even-skipped. In contrast, in the grasshopper, the engrailed
      stripes appear one at a time after the blastoderm stage as the embryo elongates.
      To address the molecular basis for this difference, we have cloned the
      grasshopper homologue of the Drosophila pair-rule gene even-skipped and show that
      it does not serve a pair-rule function in early development, although it does
      have a similar function in both insects during neurogenesis later in development.

PMID- 1350330
TI  - [Vecuronium in pediatric anesthesia. Repeated bolus vs continuous infusion].
AB  - Vecuronium bromide was employed in 26 pediatric patients; 18 received vecuronium
      infusion and 11 intermittent bolus administration. The aim of the study was to
      evaluate the pharmacodynamics of the drug, the lack of cumulative properties, the
      best infusion rate, the possible advantage of the infusion technique.
      Neuromuscular blockade monitoring was performed in all patients. In the results,
      vecuronium shows lack of cumulative properties. The best infusion rate was 0.13
      +/- 0.02 mg/kg/h. The continuous infusion allows the employment of lesser doses
      of the drug than the intermittent administration.

PMID- 1350329
TI  - [Molecular genetic studies in alpha-thalassemia].
AB  - A group of 5,000 patients, suspected of haemolytic anaemia, were investigated
      with molecular genetic methods for deletion types of alpha-thalassemia. In 776
      (15.6%) patients a deletion of one or more alpha-globin genes was found. The same
      group of patients was also investigated for abnormal haemoglobins and beta
      thalassaemia. In about 30% of the patients either an alpha-thalassaemia, an
      abnormal haemoglobin, a beta-thalassaemia, or a combination was diagnosed. In a
      group of patients with a haemoglobinopathy, the frequency of alpha-thalassaemia
      was much higher (i.e. 33%) than in individuals without haemoglobinopathy.
      Preselection of the patients based on the presence of microcytic erythrocytes
      and/or a decreased ADW0.5 of the erythrocytes gave a high incidence of false
      negative and false-positive results. Therefore, haemoglobin examination should
      not be restricted to protein chemistry, but should include molecular genetic
      investigations for deletion types of alpha-thalassaemia.

PMID- 1350331
TI  - [Analgesia-sedation during extracorporeal lithotripsy (ESWL)].
AB  - Personal experience of analgesia-sedation in ESWL is reported, stress being laid
      on the importance of anxiety treatment by means of premedication with
      benzodiazepine. In personal experience, this preventive treatment proved very
      useful in reducing the consumption of opioids and thus in rendering the pain
      experience of patients undergoing treatment less unpleasant. At the same time it
      is reported that in some patients it was necessary to administer benzodiazepines
      with a more marked hypnotic effect. In these cases, the possibility of countering
      the hypnotic effect with a specific antagonist made it possible to resort to
      these drugs in patients who were subjected to ESWL in a day-hospital regime.

PMID- 1350332
TI  - [The medical therapy of peptic ulcer. The state of the art].

PMID- 1350333
TI  - Synaptic inputs to GABAA and GABAB receptors originate from discrete afferent
      neurons.
AB  - gamma-Aminobutyric acid (GABA) inhibits neurons by acting at GABAA and GABAB
      receptors but it is not known whether the two receptors are associated with
      discretely separate afferent inputs or whether GABA released from a single
      presynaptic neuron activates both receptors. Intracellular recordings were used
      to show that, in the lateral amygdala and ventral tegmental area of the rat,
      distinct sets of GABA-containing neurons provide the synaptic input to GABAA and
      GABAB receptors. Synaptic potentials resulting from GABAA receptor activation
      (blocked by bicuculline) and from GABAB receptor activation (blocked by 2
      hydroxysaclofen) occurred spontaneously but as unrelated events. Furthermore, the
      two components of evoked synaptic potentials were differentially inhibited by
      agonists acting presynaptically (muscarine and 5-hydroxytryptamine). The finding
      that GABA acting at GABAA and GABAB receptors originates from distinct sets of
      presynaptic fibers suggests that two groups of GABA-containing neurons might be
      generally distinguishable in the mammalian nervous system.

PMID- 1350334
TI  - Extracellular adenosine 5'-triphosphate-evoked glutamate release in cultured
      hippocampal neurons.
AB  - Characteristics of extracellular ATP-evoked electrical responses in rat
      hippocampal neurons were investigated. Extracellular ATP (100 microM) induced a
      rapid depolarization followed by repetitive firings of spikes in these cells
      under whole-cell current-clamp. In whole-cell voltage-clamp experiments, ATP
      activated 2 types of inward currents that were inhibited by P2-purinoceptor
      blocker suramin (300 microM). One is a small (about -20 pA) sustained current
      which is insensitive to tetrodotoxin (TTX), and the other is a large (-100 to 
      300 pA) transient current which abolished in the presence of 3 microM TTX. The
      ATP-induced transient current was blocked by 6-cyano-7-nitro-quinoxaline-2,3
      dione (CNQX; 30 microM), a non-N-methyl-D-aspartate (non-NMDA) receptor
      antagonist. ATP failed to induce the transient current in the cell which showed
      the desensitization to quisqualic acid (QA; 10 microM), a non-NMDA receptor
      agonist. These findings suggest that ATP directly activates small sustained
      currents, and indirectly induces the transient currents by evoking glutamate
      release.

PMID- 1350335
TI  - NMDA, non-NMDA and glycine receptors mediate binaural interaction in the lateral
      superior olive: physiological evidence from mouse brain slice.
AB  - Binaural interaction was investigated in a 400 microns brain slice taken through
      the mouse lateral superior olive (LSO). Ipsilateral excitatory and contralateral
      inhibitory inputs to LSO neurons were examined by recording physiological
      responses to electrical stimulation of the trapezoid body. Bath application of
      non-N-methyl-D-aspartate (non-NMDA) antagonists blocked ipsilateral excitation
      and strychnine blocked contralateral inhibition. N-methyl-D-aspartate (NMDA) had
      little effect on ipsilateral responses but completely blocked contralateral
      inhibition. These results suggest that ipsilateral excitation is mediated by non
      NMDA receptors and contralateral inhibition by strychnine dependent glycine
      receptors. NMDA receptors may play a role by modulating contralateral inhibition
      in LSO.

PMID- 1350337
TI  - Abstracts of the 20th annual meeting of the British Nuclear Medicine Society.
      London, 6-8 April 1992.

PMID- 1350336
TI  - Reversal by pertussis toxin and N-ethylmaleimide of the facilitation of
      baroreceptor reflex response by somatostatin in the rat.
AB  - We evaluated the transmembrane signaling mechanism that may underlie the
      facilitatory action of somatostatin (SOM) on baroreceptor reflex (BRR), using
      adult, male, Sprague-Dawley rats anesthetized with pentobarbital sodium (40
      mg/kg, i.p.). Intracerebroventricular (i.c.v.) application of SOM (2 nmol)
      promoted a significant elevation in BRR response, induced by phenylephrine (5
      micrograms/kg, i.v.). This potentiatory action of the tetradecapeptide was
      significantly reversed after pretreating animals with bilateral microinjection of
      pertussis toxin (25 ng) or N-ethylmaleimide (2 nmol) into the nucleus tractus
      solitarius (NTS), the terminal site for baroreceptor afferents. These results
      suggest that a pertussis toxin-sensitive GTP-binding regulatory protein, possibly
      Gi, may be involved in the modulation of the BRR by SOM at the NTS.

PMID- 1350338
TI  - Hypnosis or cognitive behavioral training for the reduction of pain and nausea
      during cancer treatment: a controlled clinical trial.
AB  - Few controlled clinical trials have tested the efficacy of psychological
      techniques for reducing cancer pain or post-chemotherapy nausea and emesis. In
      this study, 67 bone marrow transplant patients with hematological malignancies
      were randomly assigned to one of four groups prior to beginning transplantation
      conditioning: (1) hypnosis training (HYP); (2) cognitive behavioral coping skills
      training (CB); (3) therapist contact control (TC); or (4) treatment as usual
      (TAU; no treatment control). Patients completed measures of physical functioning
      (Sickness Impact Profile; SIP) and psychological functioning (Brief Symptom
      Inventory; BSI), which were used as covariates in the analyses. Biodemographic
      variables included gender, age and a risk variable based on diagnosis and number
      of remissions or relapses. Patients in the HYP, CB and TC groups met with a
      clinical psychologist for two pre-transplant training sessions and ten in
      hospital "booster" sessions during the course of transplantation. Forty-five
      patients completed the study and provided all covariate data, and 80% of the time
      series outcome data. Analyses of the principal study variables indicated that
      hypnosis was effective in reducing reported oral pain for patients undergoing
      marrow transplantation. Risk, SIP, and BSI pre-transplant were found to be
      effective predictors of inpatient physical symptoms. Nausea, emesis and opioid
      use did not differ significantly between the treatment groups. The cognitive
      behavioral intervention, as applied in this study, was not effective in reducing
      the symptoms measured.

PMID- 1350339
TI  - Does opiate premedication influence postoperative analgesia? A prospective study.
AB  - The influence of opiate premedication on analgesic requirements postoperatively
      was investigated. Out of 98 patients with a lumbar disc prolapse 50 were
      premedicated with flunitrazepam orally, 48 with pethidine and triflupromazine
      intramuscularly. The operations were performed under inhalational anaesthesia.
      The average time up to the first demand for an analgesic was longer following
      opiate premedication (351 vs. 219 min). Only 45.8% of the patients treated with
      opiates demanded analgesics postoperatively, compared to 80.0% of those who had a
      benzodiazepine premedication (P less than 0.01). These clinical data confirm the
      experimental evidence that pretreatment with opiates diminishes the sustained
      hyperexcitation of the central nervous system caused by peripheral lesions.

PMID- 1350340
TI  - Enhancement of pentazocine analgesia by clonidine.
AB  - Opiate-adrenergic interactions were investigated by studying the effect of the
      selective alpha 2-adrenergic agonist, clonidine, on the analgesia produced by
      intravenous placebo and by the predominantly kappa-opiate agonist, pentazocine,
      in patients with dental postoperative pain. Clonidine did not affect the pain
      level when administered with intravenous placebo. When administered with
      pentazocine, clonidine caused a statistically significant increase in pentazocine
      analgesia. Comparison is made to other opiate-adrenergic interactions and
      possible mechanisms are discussed.

PMID- 1350341
TI  - Comments on I.M.C. Clarke in Pain, 45 (1991) 167-170.

PMID- 1350342
TI  - [Extrauterine adaptation. Interregional Congress of Neonatology. Asiago, October
      12, 1991].

PMID- 1350343
TI  - Is Asacol as effective as sulphasalazine in maintaining remission of Crohn's
      disease and ulcerative colitis?
AB  - To compare the efficacy of Asacol (mesalazine coated with Eudraget-S) as a
      maintenance therapy with that of sulphasalazine, relapse rates of patients with
      ulcerative colitis and Crohn's disease, treated with sulphasalazine or Asacol
      were assessed in a retrospective study. A total of 164 patients were
      investigated, 127 on sulphasalazine and 37 on Asacol. None of the patients on
      Asacol was changed from sulphasalazine because of lack of efficacy to
      sulphasalazine. Relapse rates were measured over a 4 year period. In ulcerative
      colitis these were sulphasalazine 10/77 (13.0%), Asacol 5/20 (25.0%), NS; in all
      Crohn's disease patients, sulphasalazine 12/50 (24.0%), Asacol 11/17 (64.7%); P
      less than 0.0025. In patients with Crohn's disease with ileal involvement,
      relapse rates were sulphasalazine 9/28 (32.1%), Asacol 9/11 (81.6%), P less than
      0.0125; without ileal involvement, sulphasalazine 3/22 (13.6%), Asacol 2/6
      (33.4%), NS. This study suggests that Asacol is as effective as sulphasalazine in
      maintaining remission in ulcerative colitis and in patients with Crohn's disease
      without ileal involvement. Sulphasalazine seems to be more effective than Asacol
      in maintaining remission in patients with Crohn's disease with terminal ileal
      involvement.

PMID- 1350344
TI  - Difficulties in localization and treatment of insulinomas in type 1 multiple
      endocrine adenomatosis (MEA).
AB  - A 15 year old girl with a family history of type 1 multiple endocrine
      adenomatosis presented with reversible neurological disturbances, hypoglycaemia
      and hyperinsulinaemia. Initial radiology was normal, but portal venous sampling
      suggested an insulinoma in the tail of the pancreas which was removed with
      conservation of the spleen. Hypoglycaemia persisted despite high doses of
      diazoxide and intravenous dextrose. A second laparotomy revealed a pancreatic
      endocrine tumour and sub-total pancreatectomy was performed. Histology revealed
      islet cell microadenomatosis. Hypoglycaemia persisted despite treatment with
      somatostatin analogues and 40% intravenous dextrose was required to maintain
      normoglycaemia. A possible lesion near the splenic hilum on computed tomographic
      scan was reported as a splenunculus although further peripheral, hepatic and
      portal venous sampling suggested hepatic or systemic lesions. A positron emission
      scan and selective visceral angiography suggested a lesion in the left upper
      quadrant. Acute lactic acidosis, rhabdomyolysis and renal failure supervened.
      Post mortem revealed the putative 'splenunculus' to be a residual insulinoma,
      whilst the splenic vein was thrombosed, accounting in part for discrepant venous
      sampling data. Hyperinsulinaemia in type 1 multiple endocrine adenomatosis may
      require more aggressive surgical and hormonal intervention than when dealing with
      solitary insulinomas. Insulinomas may mimic developmental abnormalities on
      computed tomographic scanning.

PMID- 1350345
TI  - Immunocytochemical localisation of an FMRFamide-like peptide in the filarial
      nematodes Dirofilaria immitis and Brugia pahangi.
AB  - Immunocytochemical techniques were used to detect FMRFamide-like immunoreactivity
      in adults of the filarial nematodes Dirofilaria immitis and Brugia pahangi. An
      FMRFamide-like peptide was also located in third- and fourth-stage larvae of D.
      immitis. Positive immunoreactivity was observed in all parasites examined,
      irrespective of developmental stage. The major areas of positive immunoreactivity
      were located in the anterior nerve ring, lateral/dorso-ventral nerves, cephalic
      papillary ganglia and lateral ganglia. No staining was seen in the intestine or
      gonads of any parasite. These results indicate that filarial worms possess a
      peptidergic component in their nervous system. The possible role of an FMRFamide
      like peptide in the control of certain physiological events is discussed.

PMID- 1350347
TI  - Proceedings of the 13th annual meeting of the IUPS Commission on Gravitational
      Physiology. Dedicated to Orr Esrey Reynolds. San Antonio, Texas, September 29
      October 3, 1991.

PMID- 1350346
TI  - Neurohumoral responses to isohemic hypervolemia: a model for weightlessness.

PMID- 1350348
TI  - Acute ethanol intoxication may not alter alpha 2-adrenoceptors in the human
      brain.
AB  - The specific binding of the alpha 2-adrenoceptor agonists [3H]clonidine and
      [3H]bromoxidine (UK 14304) was measured in the postmortem brain of ethanol
      intoxicated nonalcoholic subjects (blood ethanol concentration: 1.37 +/- 0.30
      g/l) and matched controls. In the frontal cortex, the density of binding sites
      for [3H]clonidine (Bmax = 58 +/- 7 fmol/mg protein) and [3H]bromoxidine (UK
      14304) (Bmax = 49 +/- 7 fmol/mg protein) in ethanol intoxicated subjects did not
      differ from those in the control groups (Bmax = 68 +/- 4 and 56 +/- 8 fmol/mg
      protein for the respective radioligand). The dissociation constants (KD) were
      also similar in both groups. The binding capacities (Bmax) and KD values for both
      radioligands also were found unchanged in the hypothalamus, amygdala, head of
      caudate, hippocampus and cerebellum. The results demonstrate that, contrary to
      the beta-adrenoceptor, the presence of ethanol in the human brain does not alter
      the high-affinity state of the alpha 2-adrenoceptor in the frontal cortex and
      possibly also in other brain regions.

PMID- 1350349
TI  - Effects of blockade of 5-HT2 receptors and activation of 5-HT1A receptors on the
      exploratory activity of rats in the elevated plus-maze.
AB  - Acute administration of gepirone, a 5-HT1A agonist, caused a dose dependent (1-10
      mg/kg, IP) reduction in the locomotor activity (open and closed arms) of rats
      tested in the elevated plus-maze. However, rats housed in individual cages and
      submitted to chronic treatment with gepirone (10 mg/kg PO) showed a marked
      increase in the percentages of number and time spent in the open arms as compared
      to controls. These results are compatible with the idea that the antiaversive
      effect due to long-term treatment with 5-HT1A agonists is the result of a
      progressive desensitization of the somatodendritic 5-HT autoreceptor with the
      consequent recovery of firing rate of 5-HT neurons along with an activation of
      normosensitive postsynaptic 5-HT neurons. Ketanserin caused a biphasic effects on
      the exploratory behavior of rats in the plus-maze. The lower dose (0.5 mg/kg)
      decreased the aversion to the open arms and the higher dose (1.0 mg/kg) caused an
      unspecific decrease in the overall activity of the animals. Ketanserin is
      supposed to have antagonistic action on 5-HT2 and on alpha-adrenergic receptors.
      As prazosin (0.5-1.0 mg/kg), an alpha-adrenergic receptor blocker, did not
      present any significant effect in the present work it is suggested that the
      effects of the lower dose of ketanserin was due to its high antagonistic action
      on 5-HT2 receptors.

PMID- 1350350
TI  - Effects of acute dopamine depletion on responsiveness to D1 and D2 receptor
      agonists in infant and weanling rat pups.
AB  - The behavioral responses to separate and combined administration of the D1
      agonist SKF-38393 and the D2 agonist quinpirole following acute dopamine (DA)
      depletion via alpha-methyl-p-tyrosine (AMPT) or AMPT/reserpine were examined in
      infant (10-day-old) and weanling (21-day-old) rat pups. At both ages, AMPT
      pretreatment generally had little impact on D1- or D2-agonist-induced responding,
      whereas the greater DA depletion observed following AMPT/reserpine pretreatment
      was generally associated with suppression of both D1 and D2-agonist-typical
      responding. Thus, whereas in adult animals some degree of D1 receptor activation
      by endogenous dopamine appears to be necessary for D2 responding but not vice
      versa (e.g. White et al. 1988), in young animals there appears to be a reciprocal
      co-dependence of these two receptor subtypes, with extensive DA depletion
      suppressing responding to both agonists when administered separately. At 10 days
      of age, some D1 and D2 agonist-induced behaviors that were previously blocked by
      AMPT/reserpine were reinstated following combined administration of both
      agonists. In contrast, no clear evidence for reinstatement was seen following
      administration of the combined agonists to AMPT/reserpine-pretreated weanlings,
      perhaps due to the induction of potential competing behaviors. Whereas DA
      depletion blocked many D1- and D2-induced behaviors, such depletion conversely
      promoted the expression in agonist-treated animals of a number of behaviors that
      were not normally induced by the agonists in non-depleted animals. These
      behaviors typically involved an oral component and included grooming and mouthing
      following SKF-38393 in depleted 10-day-old pups, mouthing following
      administration of either agonist to depleted weanlings, and probing and intense
      self-mutilation (forepaw and tongue biting) following the combined agonists in
      depleted weanlings. This rapid induction of potentiated agonist responsiveness
      following acute DA depletion early in life may have significant implications with
      regard to animal models for the developmental disorder of Lesch-Nyhan syndrome.

PMID- 1350352
TI  - A ketamine-induced rat model of tardive dyskinesia.

PMID- 1350351
TI  - Species differences in the mechanism through which the serotonergic agonists
      indorenate and ipsapirone produce their anxiolytic action.
AB  - The effect of three anxiolytic drugs, indorenate, ipsapirone and diazepam, on the
      burying behaviour of rats and mice was studied. All three drugs induced a
      reduction in burying behaviour interpreted as a reduction in anxiety. However, a
      species difference in the diazepam sensitivity was found: rats showed a clear
      effect after 1.0 mg/kg while already at 0.25 mg/kg an action was observed in
      mice. The serotonergic anxiolytics produced similar responses at similar doses
      (2.5-5.0 mg/kg) in both species. The serotonergic antagonists, pindolol (3.1
      mg/kg), alprenolol (5.0 mg/kg) and methiotepin (0.31 mg/kg), induced a slight
      reduction in the time spent burying but effectively counteracted the anxiolytic
      action of the serotonergic agonists in mice but not in rats. By contrast, in
      rats, the beta blocker, practolol (0.5 mg/kg), was the only drug effective in
      preventing the anxiolytic actions of ipsapirone. The combined treatment of
      indorenate and methiotepin resulted in an impairment of motor coordination and
      ambulatory behaviour in both species studied, thereby suggesting that the lack of
      effect of such combination was mediated by altering the motor behaviour. Finally,
      the reduction in ambulatory behaviour in mice produced by ipsapirone was
      effectively prevented by the antagonists methiotepin, pindolol and alprenolol
      indicating the involvement of a serotonergic receptor in this effect. From these
      results it is concluded that a different mechanism underlies the anxiolytic
      actions of indorenate and ipsapirone in mice and rats.

PMID- 1350353
TI  - Gepirone, a selective serotonin (5HT1A) partial agonist in the treatment of major
      depression.
AB  - 1. The present study assessed the potential antidepressant action of gepirone
      hydrochloride, an azapirone serotonin (5-HT1A) partial agonist in patients with
      major depression. 2. Overall, gepirone demonstrated a significant antidepressant
      activity within the entire patient group (p less than 0.001). However, when
      subjects were stratified based upon the presence or absence of DSM III-R
      melancholic features, the melancholic depressives showed little change in weekly
      depression ratings compared to patients without melancholic symptoms (p less than
      0.001). 3. Similarly, patients who were more severely ill at the pretreatment
      period had less improvement compared to those with more modest illness severity
      (p less than 0.001). 4. These observations compliment those of prior studies
      suggesting antidepressant activity for gepirone. 5. However, a consistent
      efficacy comparable to conventional neuronal reuptake inhibitor antidepressants
      remains to be established in patients with more severe depression characterized
      by melancholic features.

PMID- 1350354
TI  - Influence of some dopaminergic agents on antinociception produced by quinine in
      mice.
AB  - 1. The analgesic effect of quinine and the influence of some dopaminergic agents
      on it were studied in mice. 2. Quinine (25-130mg/kg, ip) effectively elicited
      antinociceptive effect in a dose related manner. 3. D-Amphetamine (2.5-4mg/kg,
      ip), L-dopa (25mg/kg, sc), L-dopa (25mg/kg, sc) plus benserazide (12.5mg/kg, sc),
      alpha-methyl-p-tyrosine (50mg/kg, ip) plus L-dopa (25mg/kg, sc) and pargyline
      (50mg/kg, ip) significantly attenuated the antinociceptive effect of quinine
      (50mg/kg, ip), while DOPS (4mg/kg, ip) did not affect quinine antinociception. 4.
      Pimozide (4mg/kg, ip), L-sulpiride (40mg/kg, ip), SCH 23390 (0.2mg/kg, sc) and
      alpha-methyl-p-tyrosine (50mg/kg, ip) effectively potentiated the antinociceptive
      effects of quinine (50mg/kg, ip). 5. Pimozide (4mg/kg, ip) also antagonised the
      antagonistic effect of d-amphetamine (4mg/kg, ip) on the antinociceptive effect
      of quinine (50mg/kg, ip). 6. These data indicate that quinine elicited
      antinociception dose dependently. Furthermore, the influence of pimozide, L
      sulpiride and SCH 23390 on quinine antinociception suggests the involvement of
      dopaminergic mechanisms.

PMID- 1350355
TI  - Actions of sex hormones on the brain.
AB  - 1. The brain is a target for sex steroid hormones. As a result of sex hormone
      actions on the brain various behavioral changes are observed in animal and man.
      This paper gives a brief overview over the multiple central nervous functions
      that are under modulatory control of sexual hormones and describes the complex
      sex steroid actions on the brain by giving an example for "activating" and
      "organizing" effects of estrogens on noradrenergic neurons in the brain of rats.
      2. Estradiol-17 beta induced sex specific alterations in the turnover of
      noradrenaline in the preoptic area and mediobasal hypothalamus showing "female"
      or "male" responses. 3. Neonatal manipulations of female rat pups by
      testosterone, estradiol-17 beta or 4-hydroxyestradiol-17 beta defeminized the
      "female" response of the noradrenaline turnover in the preoptic area. 4.
      Defeminization was not observed when neonatal females received the non
      aromatizable sex steroid dihydrotestosterone. 5. Activating and organizing
      effects of sex steroids on animal brain as shown here for noradrenergic neurons
      are discussed in relation to the regulation of behavior in man. Special regard is
      given to psychic disorders that might be associated with abnormalities in the
      production or metabolism of or the response to gonadal hormones.

PMID- 1350356
TI  - Lithium reduced synaptic transmission and increased neuronal excitability without
      altering endogenous serotonin, norepinephrine and dopamine in rat hippocampal
      slices in vitro.
AB  - 1. Extracellular field potentials were recorded in the CA1 pyramidal cell layer
      following stimulation of stratum radiatum in rat hippocampal slices during
      superfusion with different concentrations (1, 2, 5, 10, 20, and 30 mM) of lithium
      (Li+). Control slices were exposed similarly to choline (Ch+) or sodium (Na+). 2.
      At high concentrations (greater than or equal to 10 mM), Li+, Ch+ and Na+ reduced
      the amplitude of the field excitatory postsynaptic potential (EPSP). However, Li+
      increased, whereas Ch+ and Na+ reduced the population spike amplitude. Thus, Li+
      specifically enhanced the excitability of CA1 pyramidal cells. 3.
      Electrophysiologically monitored slices, plus an additional group exposed to Li+,
      Ch+ or Na+ without concomitant field potential recordings, were processed for
      measurement of endogenous levels of serotonin (5-HT), norepinephrine (NE) and
      dopamine (DA). The mean endogenous levels of 5-HT and NE were not significantly
      different in 1-30 mM Li+, Ch+ and Na+. Dopamine contents were unchanged after
      exposure to Li+ and Na+, but were reduced by Ch+. 4. The non-specific effects of
      Li+ on synaptic transmission and its specific effects on neuronal excitability
      appeared independent of changes in endogenous 5-HT, NE and DA levels.

PMID- 1350357
TI  - Somatostatin inhibition of gastrin gene expression: involvement of pertussis
      toxin-sensitive and -insensitive pathways.
AB  - These studies were performed to determine the intracellular pathways involved in
      regulating gastrin gene expression. The inclusion of 10(-4) M forskolin or 10(-4)
      M dibutyryl cyclic AMP (DBcAMP) in incubation medium containing dog antral mucosa
      resulted in 249% and 323% increases, respectively, in gastrin mRNA levels. The
      stimulatory effects of forskolin and DBcAMP were both inhibited significantly by
      10(-6) M somatostatin. Preincubation of antral mucosa with pertussis toxin nearly
      abolished the inhibitory effects of somatostatin on gastrin mRNA stimulated by
      forskolin, but had no effect following DBcAMP. To examine whether calcium
      dependent pathways might be involved in regulating gastrin gene expression,
      antral mucosa was incubated with increasing concentrations of calcium or the
      ionophore ionomycin. Both agents produced only modest increases in gastrin mRNA,
      which were abolished by the addition of somatostatin to the incubation medium.
      These studies indicate that somatostatin appears to inhibit gastrin gene
      expression through mechanisms involving both pertussis toxin-sensitive and 
      insensitive pathways.

PMID- 1350358
TI  - Pharmacology and biochemistry. Overview.

PMID- 1350359
TI  - Neuropharmacology of cocaine and ethanol dependence.
AB  - Drug addiction includes two important characteristics, chronic compulsive or
      uncontrollable drug use and a withdrawal syndrome when use of the drug is
      stopped. Animal models for the motivational components of drug dependence have
      been developed allowing a systematic exploration of the neurobiological
      mechanisms of drug dependence. The reinforcing actions of acute cocaine as
      measured by intravenous cocaine self-administration appear to be mediated by the
      presynaptic release of dopamine in the region of the nucleus accumbens and may
      preferentially involve the dopamine D-1 receptor subtype. The nucleus accumbens
      circuitry involved in the reinforcing actions of cocaine may include the ventral
      pallidum and may be modulated by serotonin. Chronic cocaine produces increases in
      brain reward thresholds that may reflect the "dysphoria" and anhedonia associated
      with cocaine dependence and suggests a dysregulation of brain reward systems
      possibly involving dopamine. Reliable measures for the acute reinforcing effects
      of ethanol in nondependent animals have been established in the rat using a lever
      press operant and a taste habituation procedure. Important roles have been
      established for serotonin, GABA, dopamine, and opioids in the acute reinforcing
      properties of ethanol, perhaps acting on some of the same neural circuitry
      subsuming the reinforcing actions of other drugs of abuse. Studies of the
      motivational aspects of ethanol dependence have suggested a functional role for
      brain corticotropin-releasing factor. These results suggest that the neurobiology
      of drug dependence involves not only neurotransmitters that mediate the acute
      reinforcing properties of drugs, but also the aversive motivational and emotional
      aspects of drug withdrawal. Advances in our understanding of brain changes
      associated with the switch from acute effects to chronic actions may provide a
      key to our understanding of not only drug dependence, but also psychopathology
      such as, anxiety, and affective disorders.

PMID- 1350360
TI  - Recent advances in pharmacological research on alcohol. Possible relations with
      cocaine.
AB  - Alcohol dependence is a major public health problem. Studies have shown that a
      person dependent on alcohol often coabuses other substances, such as cocaine.
      Cocaine is a powerful stimulant whereas ethanol is generally considered to be a
      depressant, with some stimulating properties. The subjective effects of these two
      substances in a dependent individual may often appear to be more similar than
      they are different. Animals also self-administer both substances. Basically,
      although both substances have anesthetic properties and both act to functionally
      increase catecholaminergic function, especially that of dopamine, there are some
      differences in their actions. Both alcohol and cocaine have various effects on
      several neurotransmitters and systems, which ultimately interact to produce the
      feeling of well-being avidly sought by many individuals today. This drive often
      eventually produces a dependence which has associated social and medical
      consequences. It seems likely that the neurochemical changes that ensue following
      abuse of these substances underlie the phenomena of dependence, tolerance, and
      subsequent withdrawal. The apparent similarities and differences between these
      two substances will be reviewed in this chapter.

PMID- 1350361
TI  - Molecular mechanisms associated with cocaine effects. Possible relationships with
      effects of ethanol.
AB  - Cocaine has been shown to be a highly addictive and toxic drug. It produces these
      effects and a variety of other physiological and behavioral effects through its
      interactions with several distinct central nervous system receptor sites. We
      present the results of a series of studies that utilized multiple site analyses
      to elucidate which cocaine binding sites influence the reinforcing and toxic
      effects of cocaine and with what proportion of influence. The nature of cocaine
      interactions with monoamine transporters is also discussed, especially with the
      dopamine transporter, which has been shown to be the cocaine binding site that is
      primarily associated with the reinforcing effects of cocaine. We also provide
      evidence that vulnerability to both the toxic and addictive effects of cocaine
      may be significantly influenced by genetic differences in both humans and
      animals. In view of the fact that cocaine is commonly abused in a polydrug
      situation, we present the results of both behavioral and biochemical experiments
      which suggest that common biochemical pathways may mediate the reinforcing or
      addictive properties of drugs of abuse. Finally, we discuss research on the
      biochemical mechanisms associated with effects of ethanol, particularly those
      which may also influence cocaine self-administration and speculate on
      pharmacotherapeutic strategies for concurrent abuse of cocaine and ethanol.

PMID- 1350362
TI  - [Congress of Pneumology of French Language. Montreal, June 1991].

PMID- 1350363
TI  - [Bronchodilator effect of salmeterol and inhibition of bronchial
      hyperreactivity].
AB  - Salmeterol is a new long acting bronchodilator which is specific for beta-2
      adrenergic receptors. Its bronchodilator effects can persist for at least 12
      hours after inhalation. This drug can inhibit the bronchoconstrictor effects of
      methacholine up to 12 hours after inhalation and this effect is proportional to
      the administered dose. Salmeterol improves daily expiratory flow rates and blocks
      exercise-induced bronchoconstriction. A 50 micrograms dose, inhaled before an
      antigenic bronchoprovocation, can markedly reduce for up to 24 hours the
      immediate and late bronchospastic responses to antigen. Moreover, salmeterol
      inhibits the increase in bronchial responsiveness induced by antigenic exposure.
      This latter effect does not seem to be related to a persisting bronchodilatation.
      The responsible mechanisms for this inhibition of allergic response or if its
      effects are only due to a functional antagonism remain to be explored. A
      particularly relevant point would be to determine of salmeterol diminishes or
      blocks the inflammatory bronchial asthmatic reaction.

PMID- 1350364
TI  - [Salmeterol and prolonged treatment of asthma: international clinical data].
AB  - Salmeterol is an original molecule with a selective-beta-2-sympathomimetic effect
      which is intended to a prolonged treatment of asthma. This inhaled preparation
      has a long duration of action which points to its use on a BID regimen. Results
      of the phase III development has been assessed in 2,277 subjects. Salmeterol
      administered at a dose of 50 micrograms morning and evening results in a marked
      increase in FEV1, which remains superior to 15% by comparison with baseline 12
      hours after the last dose in the majority of subjects. In the specific case of
      more severe asthma (FEV1 less than 50% of predicted), the use of 100 micrograms
      morning and evening allows for an extra-improvement in FEV1. In the majority of
      studies, salmeterol has resulted in an almost complete remission of the clinical
      symptomatology: disappearance or major diminution in the use of inhaled
      salbutamol administered as a rescue medication on a PRN basis (during the day and
      at night) and of nocturnal awakenings, global improvement of clinical scores.
      Daily peak expiratory flow rates (morning and night values) are considerably
      improved (greater than or equal to 50 l/min) with a significant reduction of
      daily swings. Lung function tests are also very significantly improved.
      Salmeterol has proved to be largely superior to the comparison medications,
      salbutamol taken at a dose of 200 micrograms four times a day, and optimal
      therapy with theophylline. Clinical acceptability of salmeterol is good and is
      not different from salbutamol.

PMID- 1350365
TI  - [Duration of bronchial protective effect of salmeterol in asthma induced by
      hyperventilation with dry cold air].
AB  - The duration of the blocking effect of salmeterol (50 micrograms), albuterol (200
      micrograms) and placebo was compared in a double-blind study carried out in 12
      adult asthmatic subjects who underwent hyperventilation tests with cold dry air
      on 4 study days. On the first day, the hyperventilation test was carried out at
      various time intervals with spontaneous functional recovery between each test.
      The response was assessed by interpolating the dose of cold dry air causing a 20%
      fall in FEV1 (PD20). On the three other days, the active or placebo medications
      were administered. Spirometry was assessed 15 minutes and 1 hour later. The
      hyperventilation test was then performed and repeated at various time intervals
      after administering the drug. The mean duration of the blocking effect was 0.25
      hour for placebo, 3.5 hours for albuterol, and of 15.9 hours for salmeterol.
      Eight of the 12 subjects still showed some blocking effect eight hours after
      salmeterol by comparison with only one subject after albuterol. The authors
      conclude that salmeterol has a significantly longer effect than albuterol on
      bronchoconstriction induced by hyperventilation.

PMID- 1350366
TI  - [Usefulness of salmeterol in nocturnal asthma: a comparative study with
      theophylline-ketotifen association. A French multicenter group].
AB  - Ninety-six patients with nocturnal asthma (FEV1 = 60-90% pred, reversibility
      greater than or equal to 15%, at least 2 awakenings in the week preceding the
      trial) were included in a double-blind, randomized, crossover, multicenter study
      which compared the efficacy and side effects of inhaled salmeterol (50 micrograms
      morning and evening) to the association theophylline-ketotifen (300 mg and 1 mg
      morning and evening, respectively). The trial included a run-in period of 14 days
      and 2 periods of successive treatment of 28 days each. The efficacy was expressed
      in terms of therapeutic success, defined by the total disappearance of nocturnal
      symptoms during the treatment week. A statistically significant difference (p
      less than 0.01) was found between salmeterol and the association for this
      criteria: during the first period, 46% of subjects treated by salmeterol did not
      present nocturnal awakenings during the last treatment week by comparison with
      15% of subjects taking the association; during the second period, corresponding
      figures were 39% for salmeterol by comparison with 26% for the association.
      Differences were also significant, favoring salmeterol, for other criteria (lung
      function tests, extra-need for salbutamol). Side effects were 5 times more
      frequent for the association (p less than 0.004). Salmeterol is clearly superior
      to the association theophylline-ketotifen in the treatment of nocturnal asthma.

PMID- 1350367
TI  - [Prolonged effect against exercise-induced bronchospasm: salmeterol versus sodium
      cromoglycate].
AB  - Nineteen subjects with isolated exercise-induced asthma (FEV1, FEF25-75%, PEFR,
      FVC greater than 95% predicted values, fall in FEV1 of at least 15% after
      exercise, typical recent symptoms of exercise-induced asthma, no other treatment)
      were entered in a multicenter trial carried out in a double blind, double
      placebo, cross-over manner. After a one-month baseline period, subjects underwent
      an exercise after inhaling 100 micrograms of salmeterol (n = 12) or 40 mg of
      sodium cromoglycate (n = 7). Treatments were alternated before the second
      exercise which took place at least 2 days after the first. Efficacy was assessed
      by examining changes in FEV1, FEF25-75% after exercise carried out 30 minutes and
      7 hours after administering the treatment by comparison with baseline values
      (assessments done 1, 10 and 30 minutes after exercise, lowest of three values
      kept for the analysis of each parameter). FEV1 and FEF25-75% were significantly
      higher 30 minutes after taking salmeterol. Salmeterol was found to be superior to
      sodium cromoglycate for all parameters 7 hours after administering the drug. Both
      treatments were well tolerated. This study confirms that the longer duration of
      effect of salmeterol and its superiority by comparison with the standard
      treatments of exercise-induced asthma.

PMID- 1350368
TI  - [Can the management of patients with asthma be improved at present?].
AB  - The author suggests various means to improve the management of asthma through: 1)
      a multidisciplinary approach; 2) prevention which should include reduction of
      allergenic and offending exposure; 3) a better information and education of
      asthmatic patients; 4) a more objective therapeutic follow-up; 5) a "physical
      medicine". A therapeutic improvement is also needed through a better
      comprehension of asthma by the patient and the physician. Salmeterol is a
      promising medication because of its long bronchodilator and protective effect. A
      better knowledge to define its strategic use of this new drug is needed.

PMID- 1350369
TI  - [Salmeterol: towards new perspectives in the treatment of asthma].
AB  - Asthma is now considered as an inflammatory condition and the purpose of the
      treatment is directed towards the control of inflammation. Recent therapeutic
      guidelines have been proposed and suggested the early use of antiinflammatory
      preparations. Salmeterol has a prolonged bronchodilator and protective effect
      against physical stimuli such as exercise and exposure to cold air. Clinical
      studies have all shown a superiority of salmeterol by comparison with salbutamol
      in the treatment of asthma. Recent in vitro and in vivo studies also suggest that
      salmeterol may have an extra non-bronchodilator effect. Salmeterol appears to be
      a safe preparation if administered at a dose of 50 to 100 micrograms on a BID
      regimen. It has been argued that the regular use of salmeterol can mask the
      worsening of bronchial inflammation although clinical studies have not
      substantiated this potential risk. Other studies are required to answer this
      question. A scheme incorporating salmeterol in the guidelines for the treatment
      of asthma is proposed.

PMID- 1350371
TI  - [Drugs causing augmentation of ventilation].

PMID- 1350370
TI  - [Pharmacological properties of salmeterol].
AB  - Salmeterol is an original molecule characterized by its long duration of action
      (greater than 12 hrs in humans). Salmeterol is a highly selective beta-2 agonist
      that is from 2 to 15 times more potent than salbutamol on beta-2 receptors of
      bronchial smooth muscle and 10,000 times more potent than isoprenaline on beta-1
      receptors. The duration of action of salmeterol on bronchial smooth muscle has
      been shown to be much superior than all other beta-2 sympathomimetics that have
      been studied, including formoterol. Salmeterol has two side chains that are
      linked by a long hydroxycarbon chain. Its long duration of action could be
      explained by the link to the cell membrane through an exo-site which is distinct
      from the beta-2 receptor. In vitro and in the animal model, salmeterol has a
      triple effect: inhibition of the liberation of inflammatory mediators (histamine,
      prostaglandins, leukotrienes), inhibition of cell influx and of protein
      extravasation. The relevance of this effect remains to be establish in humans.

PMID- 1350372
TI  - 3rd International Conference on Education and Training in Occupational Health and
      XIth UOEH International Symposium. Kitakyushu, Japan, 21-23 October 1991.

PMID- 1350373
TI  - From basic research in oncology to clinical application with special reference to
      cancer in women. XIXth meeting of the International Society for Oncodevelopmental
      Biology and Medicine. Siena, October 13-17, 1991. Abstracts.

PMID- 1350374
TI  - Glucagon mediates arginine-induced somatostatin secretion from isolated rat
      pancreatic islets.
AB  - Glucagon has been suggested to be a mediator of intra-islet paracrine effect of
      insulin and somatostatin during nutritive stimulation. The aim of this study was
      to reveal possible intra-islet interactions between insulin, somatostatin and
      glucagon in a batch stimulation model with isolated pancreatic islets. Such
      interactions may influence stimulus-secretion experiments in this experimental
      model. In our hands arginine stimulated somatostatin secretion only in the
      presence of insulin antiserum. Furthermore, arginine-induced glucagon secretion
      was greatly increased following addition of insulin antiserum. The addition of
      glucagon antiserum inhibited these effects of insulin antiserum on somatostatin
      secretion. In conclusion, glucagon apparently represents the central mediator of
      arginine effects on somatostatin secretion in isolated rat pancreatic islets in
      batch stimulation experiments.

PMID- 1350375
TI  - Time-related decrease in diffusion capacity in HIV-infected patients with
      impaired immune function.
AB  - The purpose of this study was to investigate acute and time-related changes in
      lung function, i.e. forced expiratory volume in 1 second (FEV1), vital capacity
      (VC) and transfer factor (KCO) in HIV-infected patients with CD4 cell counts less
      than 400 x 10(6)/l. 66 males with no history of HIV-related pulmonary symptoms
      participated in a prospective lung function study for 9 months with 3-month
      intervals between examinations. 15/66 patients (23%) developed acute pulmonary
      symptoms, i.e. dyspnea (n = 12), cough (n = 13), fever greater than 38 degrees C
      (n = 13) and interstitial infiltrates on the X-ray (n = 9). Among the 51
      asymptomatic patients, a significant time-related decrease in KCO (median
      decrease of 7%) was found, whereas no significant change in FEV1 or VC was
      observed during the study. Baseline KCO, i.e. KCO at entry, was found to be
      significantly higher in the asymptomatic patients (102% predicted (pred.) than in
      those patients who developed pneumonia (88% pred.). Development of pulmonary
      symptoms was both followed by a significant decrease in KCO (median decrease
      17%), FEV1 and VC. We therefore conclude that HIV-infected patients with impaired
      immune function have in the absence of pulmonary symptoms a decrease in KCO. In
      case of pneumonia an acute decrease in both KCO, FEV1 and VC occurs.

PMID- 1350377
TI  - Somatostatin receptor imaging of endocrine gastrointestinal tumors.
AB  - Somatostatin receptors are present on various tumors of neuroendocrine origin. We
      recently developed a technique for the in vivo visualization of somatostatin
      receptor positive tumors, which offers a powerful alternative to tumor imaging
      with labeled monoclonal antibodies. Instead of injecting radiolabeled antibodies
      against the somatostatin receptor, we labeled a somatostatin analogue ([Tyr3]
      octreotide) which is known to bind specifically to the somatostatin receptor, and
      injected this labeled hormone analogue in order to visualize somatostatin
      receptor positive tumors. We previously reported the successful visualization of
      the primary tumors or metastases of various endocrine gastrointestinal tumors
      after injection of the iodinated somatostatin analogue [123I-Tyr3]-octreotide.
      The primary tumors or metastases of 12 out of 13 carcinoids, 3 out of 3
      gastrinomas, 2 out of 4 insulinomas, and 1 out of 1 somatostatinoma were
      visualized. Using 111In-coupled octreotide, we were able to visualize 19 out of
      19 carcinoids, 7 out of 7 gastrinomas, 4 out of 7 insulinomas, 1 out of 1
      glucagonoma, and 3 out of 3 non-functioning endocrine pancreatic tumors, but none
      of 18 exocrine pancreatic tumors. In a large proportion of patients with
      endocrine gastrointestinal tumors, previously unrecognized metastases were
      demonstrated. Also, the absence or presence of in vivo visualization of these
      tumors after the injection of radiolabeled octreotide seems to predict the
      ability of octreotide therapy to control symptoms caused by hormonal secretion
      from these tumors. IN CONCLUSION: 111In-octreotide scintigraphy is a simple and
      sensitive technique for localizing of the primary tumor and its metastases in the
      majority of patients with carcinoids or endocrine pancreatic tumors.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1350376
TI  - [Biological markers of alcoholism].
AB  - Since most patients with an alcohol problem downplay their alcohol consumption,
      reliable tests for detection of alcohol abuse would be of value in clinical
      practice. Single determinations of common laboratory tests such as gamma-glutamyl
      transpeptidase, transaminases or mean corpuscular volume are only of limited
      reliability in detecting alcohol abuse. Most newer parameters, including the
      serum ASAT/ALAT ratio, the ratio of mitochondrial to total ASAT in serum, and
      serum levels of acetaldehyde-hemoglobin adducts or of antibodies against
      acetaldehyde adducts, still do not allow us to discriminate reliably enough
      between alcoholic and nonalcoholic liver diseases. beta-hexosaminidase activity
      and desialylated transferrin levels in serum appear to be the most promising
      tests for detecting alcohol abuse in the future. They require, however,
      additional validation and technical simplification respectively before they are
      suitable for daily clinical use. Thus, it remains valid that no single test can
      replace a careful history, clinical examination and laboratory results in
      detecting patients with alcohol problems.

PMID- 1350378
TI  - [Acral vasospasm in Crohn's disease].
AB  - 55 patients with Crohn's disease and 55 sex- and age-matched healthy controls
      were studied by nailfold capillary microscopy for evidence of microcirculatory
      abnormalities. Digital capillary blood flow measurements in combination with a
      local cooling test were assessed by videocapillaroscopy using the flying-sport
      technique. We found a blood flow stop with cold exposure in 44 of the 55 patients
      with Crohn's disease (mean duration 39 seconds) but in 5 of the 55 control
      subjects only (mean duration 19 seconds). There was no significant difference in
      skin temperature between the two groups. Intravital microscopy of nailfold
      capillaries revealed a marked reduction in capillary density (p less than 0.001)
      compared to normal subjects. The association of vasoconstrictive reaction in
      finger microcirculation of patients with Crohn's disease suggests a vasospastic
      tendency in this disorder.

PMID- 1350379
TI  - Recovery from experimental parkinsonism in primates with GM1 ganglioside
      treatment.
AB  - A parkinsonian syndrome can be produced in nonhuman primates by administration of
      the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Parkinsonian
      like symptoms induced acutely by MPTP were ameliorated after treatment with GM1
      ganglioside, a substance shown to have neurotrophic effects on the damaged
      dopamine system in rodents. Treatment with GM1 ganglioside also increased
      striatal dopamine and metabolite levels and enhanced the dopaminergic innervation
      of the striatum as demonstrated by tyrosine hydroxylase immunohistochemistry.
      These results suggest that GM1 ganglioside may hold promise as a therapeutic
      agent for the treatment of Parkinson's disease.

PMID- 1350380
TI  - New clue found to oncogene's role in breast cancer.

PMID- 1350381
TI  - Identification of heregulin, a specific activator of p185erbB2.
AB  - The proto-oncogene designated erbB2 or HER2 encodes a 185-kilodalton
      transmembrane tyrosine kinase (p185erbB2), whose overexpression has been
      correlated with a poor prognosis in several human malignancies. A 45-kilodalton
      protein heregulin-alpha (HRG-alpha) that specifically induced phosphorylation of
      p185erbB2 was purified from the conditioned medium of a human breast tumor cell
      line. Several complementary DNA clones encoding related HRGs were identified, all
      of which are similar to proteins in the epidermal growth factor family. Scatchard
      analysis of the binding of recombinant HRG to a breast tumor cell line expressing
      p185erbB2 showed a single high affinity binding site [dissociation constant (Kd)
      = 105 +/- 15 picomolar]. Heregulin transcripts were identified in several normal
      tissues and cancer cell lines. The HRGs may represent the natural ligands for
      p185erbB2.

PMID- 1350382
TI  - G protein activation of a hormone-stimulated phosphatase in human tumor cells.
AB  - The growth-inhibiting peptide hormone somatostatin stimulates phosphotyrosine
      phosphatase activity in the human pancreatic cell line MIA PaCa-2. This hormonal
      activation was mediated by a pertussis toxin-sensitive guanosine 5'-triphosphate
      binding protein (G protein) in the membranes of these cells. Activation of this G
      protein by somatostatin stimulated the dephosphorylation of exogenous epidermal
      growth factor receptor prepared from A-431 cells in vitro. This pathway may
      mediate the antineoplastic action of somatostatin in these cells and in human
      tumors and could represent a general mechanism of G protein coupling that is
      utilized by normal cells in the hormonal control of cell growth.

PMID- 1350383
TI  - Heteromeric NMDA receptors: molecular and functional distinction of subtypes.
AB  - The N-methyl D-aspartate (NMDA) receptor subtype of glutamate-gated ion channels
      possesses high calcium permeability and unique voltage-dependent sensitivity to
      magnesium and is modulated by glycine. Molecular cloning identified three
      complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A
      (NR2A), NR2B, and NR2C, which are 55 to 70% identical in sequence. These are
      structurally related, with less than 20% sequence identity, to other excitatory
      amino acid receptor subunits, including the NMDA receptor subunit NMDAR1 (NR1).
      Upon expression in cultured cells, the new subunits yielded prominent, typical
      glutamate- and NMDA-activated currents only when they were in heteromeric
      configurations with NR1. NR1-NR2A and NR1-NR2C channels differed in gating
      behavior and magnesium sensitivity. Such heteromeric NMDA receptor subtypes may
      exist in neurons, since NR1 messenger RNA is synthesized throughout the mature
      rat brain, while NR2 messenger RNA show a differential distribution.

PMID- 1350384
TI  - Biliary laser lithotripsy.
AB  - Laser lithotripsy is an excellent method of fragmenting those biliary stones that
      cannot be removed easily by less technically advanced methods such as basket
      extraction. The energy can be delivered through fine flexible fibers, around 200
      to 320 microns in diameter, that can be passed through the channels of a variety
      of small endoscopes. Currently, the optimal laser seems to a pulsed system
      because of the conversion of light to acoustic energy with minimal heating of the
      surrounding tissues, thus avoiding the chance of tissue injury and perforation.
      The best wavelength seems to be 504 nm, because at this wavelength, there is
      maximum absorption of laser energy by pigment stones, resulting in fragmentation
      using low-energy pulses. With further research, optimal wavelengths and pulse
      durations may emerge.

PMID- 1350385
TI  - Mechanism of action of taxol.

PMID- 1350386
TI  - Postnatal development of T-lymphocyte subpopulations in the intestinal
      intraepithelium and lamina propria in chickens.
AB  - Postnatal development of various T-lymphocyte subpopulations expressing CD3, CD8,
      CD4, and antigen-specific TCR heterodimers alpha beta (TCR2) or gamma delta
      (TCR1) was investigated in two different inbred chicken strains, SC and TK. The
      ratios of jejunum T-cells expressing TCR1 to TCR2 in the intraepithelium of SC
      and TK strains gradually increased after hatching and were 3.40 and 4.28 by 12
      weeks in TK and SC chickens respectively. The ratios of TCR1+ to TCR2(+)-cells in
      intraepithelium and the lamina propria in SC chickens were 0.96 and 1.23 at 8
      weeks and 4.29 and 2.15 at 12 weeks, respectively. Jejunum intraepithelial
      lymphocytes expressing the CD8 antigen increased gradually until 4-6 weeks of age
      and subsequently declined as chickens aged. CD4(+)-cells represented a minor
      subpopulation among the intestinal lymphocyte subpopulations. Therefore, the
      composition of various T-cell subpopulations in the intestine depended upon host
      age, the regions of the gut examined and host genetic background. These results
      suggest that changes in T-cell subpopulations in the intestine may reflect age
      related maturation of the gut-associated lymphoid tissues.

PMID- 1350388
TI  - [Effect of antibiotics on expression of virulence-associated genes].

PMID- 1350389
TI  - European Intestinal Transport Group, 11th meeting. York, England, 29 March-1
      April 1992. Abstracts.

PMID- 1350387
TI  - Completion pancreatectomy following pancreaticoduodenectomy: clinical experience.
AB  - While pancreaticoduodenectomy is today performed with an operative mortality of
      less than 5%, the incidence of significant operative morbidity remains at least
      25%. Albeit rarely, completion pancreatectomy during the early postoperative
      period may be required to manage uncontrolled pancreatic anastomotic leaks. From
      1964 to 1988, pancreaticoduodenectomy was performed on 479 patients at our
      institution, 178 (37%) of whom required re-operation in the early postoperative
      period. Of these, 11 (6%) patients underwent completion pancreatectomy at a mean
      interval of 18 days following Whipple resection. The indications prompting re
      operation included a suspected pancreatic leak (n = 8), intraabdominal hemorrhage
      (n = 2), and pancreaticocutaneous fistula (n = 1). Operative findings
      necessitating completion pancreatectomy included pancreatic anastomotic
      dehiscence with severe surrounding inflammation/necrosis prohibiting
      reanastomosis or repair (n = 10) and necrotizing pancreatitis with uncontrolled
      hemorrhage (1). Seven (64%) of these 11 patients died postoperatively of sepsis
      and multiple organ failure. The mean hospital stay in the 4 surviving patients
      was 46 days (range, 26 to 53 days). These 4 patients survived for a mean period
      of 24 months following hospital dismissal.

PMID- 1350390
TI  - Drugs recently released in Belgium. Esmolol--oxcarbazepine.

PMID- 1350391
TI  - Cutaneous innervation in chronic renal failure patients. An immunohistochemical
      study.
AB  - Most chronic renal failure patients suffer from generalized pruritus. An
      involvement of cutaneous nerve terminals in the pathogenesis of uremic pruritus
      has been suggested. Skin specimens from 24 uremic patients and 10 healthy
      subjects were processed with an indirect immunofluorescence method to investigate
      the presence and distribution of a number of neuronal markers and neuropeptides.
      No difference was found between the two groups in the distribution pattern of the
      positive nerve fibres. However, a reduction in the total number of skin nerve
      terminals in the uremic patients was detected. No correlation could be found
      between the immunohistochemical findings and the clinical features. Our results
      suggest that the skin innervation is altered in most chronic renal failure
      patients, possibly as a consequence of neuropathy.

PMID- 1350392
TI  - Cholinergic and adrenergic sweating in atopic dermatitis.
AB  - Sweating responses to methacholine and adrenaline were compared with an
      evaporimeter in normal-looking back and forearm skin from patients with atopic
      dermatitis (AD) and from non-atopic controls (NA). With both stimulants, the
      sweat rates were higher in forearm than in back skin in both groups, and between
      the two sites the rates showed positive correlations which were statistically
      significant in both groups. With methacholine the responses were slightly
      depressed in both areas in AD. With a low suprathreshold adrenaline concentration
      (5 x 10(-6) mol/l) the responses were equal in both groups but a tenfold higher
      adrenaline concentration elicited an increase of 55% in sweating rates in the
      back skin of NA and a 15% depression in the back skin of AD subjects (p less than
      0.05). On arm skin there was a similar trend, but less marked. Between the
      cholinergic and adrenergic sweating responses a positive correlation was found on
      arm skin in AD, suggesting that the unknown mechanism of sweat depression in AD
      might be the same for both drugs.

PMID- 1350393
TI  - Impairment of some granulocyte functions in Sweet's syndrome.
AB  - Chemotaxis, phagocytic and intracellular killing activities of polymorphonuclear
      leukocytes (PMNL) were investigated in vitro in 7 patients suffering from the
      acute phase of Sweet's syndrome. A moderate but consistent impairment of
      neutrophilic chemotactic activity (NCA) was revealed in all patients.
      Intracellular killing of blastospores of Candida albicans was diminished in 5/7
      patients. Phagocytosis and oxidase activities were within normal levels. These
      results point to an alteration of some PMNL functions in the acute phase of
      Sweet's syndrome.

PMID- 1350394
TI  - Evaluation of thyroid function and anti-thyroid autoantibodies in systemic
      sclerosis.
AB  - Parameters of thyroid metabolism, and the presence of anti-thyroid antibodies
      were investigated in 43 patients with systemic sclerosis. Anti-thyroid antibodies
      were detected in 14 cases. Elevated levels of anti-thyroglobulin antibodies were
      determined in 4 cases, anti-thyroid peroxidase (TPO) antibodies in 11, and anti
      microsomal antibodies in 5. The detection of anti-TPO antibodies gave the most
      remarkable information about the presence of autoimmune thyroiditis. The patients
      with anti-TPO and/or reduced T3 concentration tended to have secondary Sjogren's
      syndrome. Our results provide further evidence that anti-thyroid antibodies might
      be responsible for the remarkable appearance of autoimmune thyroiditis in
      systemic sclerosis.

PMID- 1350395
TI  - Skin cancer after renal transplantation: the causal role of azathioprine.
AB  - In 167 unselected patients with renal allografts, after a lag of 3.5 years the
      prevalence of dysplastic keratotic lesions increased linearly by 6.8%/yr and
      number of lesions also increased. There was no relationship to sun exposure or
      skin type. Malignancies occurred in 5 patients after 9 years. Viral warts
      occurred in 42% but prevalence and extent were not related to time after
      transplantation or keratoses. Comparison with other drugs and diseases suggests
      malignant keratoses are initiated in two stages by the cytotoxic effect of
      azathioprine, the role of immunosuppression remaining unproved. Psoriasis and
      eczema remitted and the prevalence of zoster and fungal disease increased. P.
      orbiculare (but not P. ovale) infection increased, unlike in other states of
      immunosuppression, suggesting the organisms are distinct, not transitional, and
      differently influenced by the different immunodeficient states induced by drugs
      and disease.

PMID- 1350396
TI  - Indication for the identity of palmoplantar keratoderma type Unna-Thost with type
      Vorner. Thost's family revisited 110 years later.
AB  - Palmoplantar keratoderma (PPK) type Unna-Thost is known to be the most common
      form of a hereditary disorder of keratinization of palms and soles. The disease
      is clinically identical with PPK type Vorner which is histologically
      characterized by epidermolytic hyperkeratosis. By reinvestigation of the family
      originally seen by Thost in 1880, the features of epidermolytic hyperkeratosis
      were found histologically confirming the diagnosis PPK of Vorner. This proves the
      identity of PPK type Thost with PPK of Vorner. Because of the histological
      variability of epidermolytic hyperkeratosis, detailed light and electron
      microscopic studies are necessary in cases of diffuse types of PPK.

PMID- 1350397
TI  - Regional distribution of melanocytic naevi in relation to sun exposure, and site
      specific counts predicting total number of naevi.
AB  - The role of exposure to ultraviolet light in the formation of melanocytic naevi
      was analysed by investigating the regional naevus distribution in 310 subjects
      (30-50 years) from a Swedish census file. The lateral aspect of the arms and the
      back had the largest concentration of naevi. The mean naevus count per unit
      surface area was higher in intermittently exposed than in rarely exposed skin (p
      less than 0.001), while the lowest mean count was found in chronically exposed
      skin. These results support the idea that intermittent exposure to ultraviolet
      light has a "naevogenic" effect while chronic exposure might be protective.
      Dysplastic naevi had a distribution pattern quite different from common naevi.
      Considering the distribution pattern solely, dysplastic naevi seem to develop
      independently of exposure to ultraviolet light. The numbers of naevi in different
      skin areas were tested for their power in predicting the total body naevus count.
      The strongest correlations were found between total counts and counts on the
      anterior surface of the thighs and the lateral aspect of the arms. Counts from
      any of these areas will provide a practical and satisfactory estimate of the
      total number of naevi.

PMID- 1350398
TI  - Group G streptococcal infections on a dermatological ward.
AB  - Groups A, B, C and G streptococci were cultured from 63 consecutive in-patients
      recruited between November 1987 and April 1988 and monitored until the end of
      July 1988. Chronic leg ulcers were present in 34 patients. Group G was found in
      34 patients, 25 of whom had pyoderma and 3 had sepsis. Six of the patients had no
      signs of clinical infection, and treatment with antibiotics was therefore
      withheld. Recurrent phlegmon or erysipelas developed in 2 of 28 patients with
      clinical Group G infections. Erysipelas developed some 1-7 months later in 3 of
      the 6 patients who were not initially treated. No significant difference in
      severity or additional medical conditions was found between the patients with
      either Group G or Group A streptococci. In comparison, data on all streptococcal
      cultures at the Department indicated that Group G was isolated 2.6 times as often
      as Group A streptococci for the in-patients, compared with 1.1 for all patients
      seen. It is concluded that Group G streptococcal skin infections must be regarded
      with the same clinical vigilance as Group A infections.

PMID- 1350399
TI  - The unexpectedly rapid response of fungal nail infection to short duration
      therapy.
AB  - To test our hypothesis that, by laying down a fungicidal barrier in the growing
      nail, a short course of antifungal therapy should be effective against
      onychomycosis, we treated 8 subjects with Trichophyton rubrum nail infection with
      terbinafine 125 mg b.d. for 14 days. All but one patient showed marked
      improvement, and 80% of fingernails and 37% of toenails were clinically cured
      after 6 months. Although this confirmed our prediction, the onset of response
      measured by outward movement of affected nail and negative cultures from distal
      nail clippings occurred after as little as 4 weeks. This was too soon for a
      fungicidal barrier to have grown out and indicates that the drug must have been
      carried directly into the diseased distal nail, presumably from newly formed
      ventral nail beneath it. The findings show that 1) short duration therapy,
      perhaps even a single dose, is possible in fungal nail infections; 2) the ventral
      nail provides unexpectedly rapid access of drugs to the site of distal disease.

PMID- 1350400
TI  - A double-blind study of superficial radiotherapy in psoriatic nail dystrophy.
AB  - In a double-blind controlled study, superficial radiotherapy (SRT) was given to
      psoriatic fingernails as three fractionated doses of 150 cGy (90 kV, 5 mA, 1.00
      mm aluminium filter). The treated nails demonstrated a significant fall in
      scoring on a clinical rating scale 10 and 15 weeks after therapy (mean scores =
      4.4 and 4.6 respectively) when compared with a mean pretreatment score of 5.5 at
      week 0 (p less than 0.0001 and p less than 0.05 respectively); the treated nails
      also showed significant clinical improvement when compared with the sham-treated
      nails at weeks 10 and 15 (p less than 0.05). Mean nail thickness in treated nails
      15 weeks after therapy was significantly thinner (mean thickness = 0.75 mm) than
      that of sham-treated nails (0.88 mm, p = 0.005), but the difference was not
      significant at week 20. The rate of linear nail growth was unaffected. SRT
      appears to confer a definite albeit temporary benefit on psoriasis of the nails
      at this dosage.

PMID- 1350401
TI  - Mucosal desquamation in psoriasis.
AB  - Urinary epithelial cell counts were determined in 102 patients with active plaque
      psoriasis. Cell counts were significantly higher in psoriatic patients than in
      the controls. A significant fall in the cell counts was observed after regression
      of psoriasis.

PMID- 1350402
TI  - Lysozyme and IgA concentrations in serum and saliva from psoriatic patients.
AB  - Significantly lower lysozyme concentrations were found in saliva of 15 psoriatic
      patients compared with controls, whereas in serum, lysozyme activity, was
      significantly higher than in controls. The concentrations of IgA in serum of
      psoriatic patients were significantly higher than in controls, whereas in
      patients' saliva IgA concentrations were not significantly different from the
      controls. The findings indicate that lysozyme and IgA may be of significance in
      the pathophysiology of psoriasis.

PMID- 1350403
TI  - The hair root pattern in psoriasis of the scalp.
AB  - Several reports suggest that a localized effluvium of scalp hair may occur in
      patients with psoriasis. The percentages of telogen and catagen hair have been
      claimed to be normal or increased in isolated cases. In the present study the
      anagen/telogen ratio was quantified under standardized conditions in psoriatic
      plaques and uninvolved areas of the scalp in 22 patients and the scalp of 22
      normal controls. This assessment was carried out by light microscopic analysis of
      hair roots, obtained by the hair pluck-method. A consistent increase in the
      percentages of telogen and catagen hair was shown in psoriatic plaques, compared
      with the uninvolved areas. Compared with the scalp of normal controls, this
      percentage was significantly increased in psoriatic plaques, but not in the
      uninvolved areas.

PMID- 1350404
TI  - Folliculitis decalvans. Long-lasting response to combined therapy with fusidic
      acid and zinc.
AB  - In 3 patients, the diagnosis of folliculitis decalvans was based on clinical,
      histopathological and laboratory criteria. All patients responded to a
      combination therapy consisting of oral and topical fusidic acid and oral zinc
      sulphate. The follow-up period exceeded more than one year.

PMID- 1350406
TI  - Acne in pubertal boys undergoing treatment with androgens.
AB  - In the present study, the development of acne lesions was studied in boys deemed
      to be too tall, for which they were treated with injections of androgens. In a
      retrospective and a prospective group of pubertal boys, an increased incidence of
      acne was observed as a consequence of treatment with androgens.

PMID- 1350405
TI  - Eosinophilic pustular folliculitis (Ofuji's disease) and non-Hodgkin lymphoma.
AB  - The authors report the third case of eosinophilic pustular folliculitis (EPF)
      associated with a non-Hodgkin lymphoma. The dermatosis occurred after an
      autologous bone marrow transplantation performed as treatment for the
      lymphoproliferative disorder. Although EPF was initially described as an
      idiopathic disease, the association of some cases with immunologic alterations or
      diseases, such as immunodeficiencies, suggests a possible immunopathologic event
      in the pathogenesis of EPF.

PMID- 1350407
TI  - A double-blind comparison of acitretin and etretinate in the treatment of
      Darier's disease.
AB  - The objective of this double-blind study was to compare the therapeutic effects
      of acitretin with those of etretinate in patients with Darier's disease. Twenty
      six patients (10 males and 16 females) were included in the study. Patients were
      treated with 30 mg daily for the first 4 weeks and with an individually adjusted
      dose (10-50 mg/day) for the subsequent 12 weeks. Remission or marked improvement
      was obtained in 10 of the 13 acitretin-treated patients and in 8 of the 11
      etretinate-treated patients who completed the 16-week treatment. The usual
      mucocutaneous adverse reactions of retinoids were observed in all but one
      patient. There were no significant differences between treatment groups with
      regard to the incidence of these reactions.

PMID- 1350408
TI  - Correlation between cutaneous sarcoidosis and systemic sarcoidosis.
AB  - Twenty patients with cutaneous sarcoidosis and 21 patients carrying isolated skin
      sarcoids were studied. (We use the term 'sarcoid' to emphasize that exclusively
      skin was altered.) Both groups were compared by clinical and histological
      patterns and certain data concerning the state of the mononuclear phagocyte
      system (MPS). It was found that skin lesions in sarcoids and sarcoidosis do not
      differ regarding either in clinical or histological manifestations. The changes
      in the functional activity of monocytes and macrophages were the same. The data
      obtained allow us to suggest that sarcoids should be regarded as a systemic
      disease connected with changes in the MPS reaction.

PMID- 1350409
TI  - Linear alopecia mucinosa along Blaschko lines.
AB  - We present a case of linear reversible non-inflammatory alopecia mucinosa in a 25
      year-old Nigerian patient. The patient exhibited an arciform bald patch on the
      scalp and follicular mucinosis in both lesions. The possible relationships
      between the unusual linear arrangement of alopecia mucinosa along Blaschko's
      lines and lichen striatus are discussed.

PMID- 1350410
TI  - Gingival hyperplasia induced by erythromycin.

PMID- 1350411
TI  - Parathyroid hormone related protein is localized in the granular layer of normal
      skin and in the dermal infiltrates of mycosis fungoides but is absent in
      psoriatic lesions.
AB  - Biopsies of normal and diseased skin were immunohistochemically investigated for
      the presence of parathyroid hormone-related protein (PTH-rp). In normal skin and
      several skin disorders a monoclonal antibody against the 34-68 sequence of PTH-rp
      was found to be exclusively located in the granular layer. PTH-rp could not be
      detected in untreated psoriatic plaque lesions even when a granular layer was
      present. Psoriatic lesions improving after 1-2 weeks' treatment with
      betamethasone or vitamin D3 analogue revealed PTH-rp reactivity just above the
      granular layer. These findings substantiate a possible role for PTH-rp as a
      growth inhibitor. In the dermis the granular layer in the upper part of the hair
      follicles was stained for PTH-rp and the dermal infiltrates in 5 of 10 patients
      were stained with mycosis fungoides.

PMID- 1350412
TI  - Oral acitretin in psoriasis: drug and vitamin A concentrations in plasma, skin
      and adipose tissue.
AB  - The purpose of the present study was to determine the concentrations of acitretin
      and its main metabolite, 13-cis acitretin, in epidermis, subcutis and plasma in
      twelve psoriatic patients treated with 30 mg acitretin orally daily for 6 months.
      In addition, endogenous concentrations of vitamin A were monitored. Blood samples
      and biopsies from normal appearing skin were obtained prior to therapy, after 1
      and 6 months of treatment and finally 1 month after cessation of therapy. Using a
      highly sensitive liquid chromatography method concentrations of synthetic
      retinoids and endogenous retinoid (retinol, 3,4-didehydroretinol) were analysed
      in hydrolyzed tissue samples and plasma. Steady-state concentration of acitretin
      in epidermis (17 +/- 9 ng/g) was reached within 1 month of therapy. There was a
      significant correlation between the individual plasma trough value and the
      epidermal concentration of acitretin after 1 month of therapy. The acitretin
      concentrations in subcutis varied from 15 to 1437 ng/g, but the mean values at 1
      and 6 months of therapy were similar (177 and 227 ng/g, respectively). After
      stopping therapy the acitretin level was below the detection limit in both
      epidermis and serum within 1 month in 9 out of 12 patients. In contrast, only 3
      of the patients were negative for acitretin in subcutis biopsies obtained 1 month
      after stopping therapy. The occurrence of a presumed tissue contaminator with
      characteristics similar to 13-cis acitretin prevented quantitation of this
      metabolite in many subcutis samples. The epidermal, subcutis and serum
      composition of retinol and 3,4-didehydroretinol remained unchanged during
      therapy, indicating no or only minimal interaction between acitretin and
      endogenous vitamin A metabolism.

PMID- 1350413
TI  - Suction blister fluid histamine in fixed drug eruption.
AB  - The histamine concentration was measured from suction blister fluid obtained from
      normal and lesional skin of 8 patients with fixed drug eruption (FDE) caused by
      phenazone salicylate and from that of 2 healthy control subjects. In blister
      fluid samples obtained before peroral challenge with phenazone salicylate, the
      histamine concentrations were below 5 nmol/l both in uninvolved skin and in sites
      of previous FDE lesion (sample 0). After challenge, samples were taken from the
      incipient reaction that was visible after an average of 155 min. Histamine levels
      were significantly elevated in the blister fluid of 2 out of 8 FDE lesions (200
      and 640 nmol/l) but in none of the uninvolved skin (sample 1). Two hours later
      (sample 2) the histamine levels were elevated in both uninvolved (mean 51.4
      nmol/l) and lesional skin (mean 168 nmol/l). After 24 h (sample 3) the
      corresponding mean value was 25.4 nmol/l for uninvolved skin and 108 nmol/l for
      lesional skin. The histamine values in the blister fluid from FDE lesions in
      samples 2 and 3 were significantly higher (p less than 0.05) than those in the
      control blisters of uninvolved skin. An elevation of histamine levels comparable
      to that in the uninvolved skin of FDE patients was seen in the 2 healthy control
      subjects studied. The present study provides direct evidence of early release of
      histamine from mast cells or basophils in FDE and suggests that histamine is one
      of the mediators of clinical symptoms of FDE.

PMID- 1350414
TI  - Cross-reactivity to palladium and nickel studied in the guinea pig.
AB  - In recent years there have been several reports on concomitant patch test
      reactions to palladium and nickel, which belong to the same group in the periodic
      table. Exposure to palladium mainly takes place via dental alloys and jewelry.
      However, the clinical relevance of simultaneous reactivity to these metals is
      unknown. To elucidate the question of cross-reactivity, guinea pigs were induced
      with palladium or nickel and simultaneously challenged with palladium and nickel.
      Animals sensitized to palladium according to the guinea pig maximization test
      method (GPMT) or to a new method by van Hoogstraten & Scheper (H&S) reacted to
      palladium as well as to nickel. On the other hand, animals sensitized to nickel
      according to H&S reacted to nickel but not to palladium. The GPMT shows that
      palladium is a more potent sensitizer than nickel: could palladium be the primary
      sensitizer in humans?

PMID- 1350415
TI  - Simple system to irradiate cultured cells with UVA light.
AB  - We developed a simple system for the irradiation of cultured cells with
      ultraviolet-A (UVA) light, and used it to study the colony-forming ability of
      fibroblasts in culture after UVA treatment. The system requires an ordinary clean
      bench, and the other materials and devices needed, such as dishes with a 35-mm
      diameter, plate glass, and 15-W UVA lamps, are easy to obtain and assemble.
      Neither stirring nor cooling of cells is required, because the fan of the clean
      bench acts as a cooler, and cells are irradiated from the bottom after they have
      settled in the dish. The UVA light incident on cells after its passage through
      both the plate glass and the bottom part of the dish contains so little of UVB
      wavelengths that cell killing by pyrimidine dimers was negligible.

PMID- 1350416
TI  - [Statistical study of a series of cryptorchism cases].
AB  - A study was made on a series of 348 patients with uni- and bilateral cryptorchid,
      a right location being predominant in the former cases, and in the canaliculus
      the most common testicular one. The associated pathology is usually irrelevant.
      In view of the results revealed by optical and ultrastructural histological
      study, the introduction of definitive corrective medical treatment appears to be
      essential within 2 years. Despite existing discrepancies with regard to dosage
      and efficacy of hormonal therapy with HCG or LH-RH analogues we believe they
      should be used at doses no higher than 12000 IU of HCG in order to achieve a
      decrease or ease the surgical treatment. Higher doses would damage the testicle
      or produce early puberty with growth failure. Scrotum-bound funiculolysis is the
      procedure accomplishing a larger amount of therapeutic success and in our
      experience the results are conditioned to the testicle's anatomic location. In
      the event of abdominal testicles or with high canaliculus location, a section of
      the spermatic canals could be performed followed later by auto-transplantations
      using microsurgery procedures.

PMID- 1350417
TI  - A word to the wise on drug diversion.

PMID- 1350419
TI  - Eye movements: a new psychotherapeutic tool.

PMID- 1350418
TI  - Aging: nutrition and the quality of life. Proceedings of a conference. Marbella,
      Spain, November 12-14, 1990.

PMID- 1350420
TI  - Thermogenesis and fructose metabolism in humans.
AB  - Resting metabolic rate was measured in 10 healthy volunteers (25 yr, 73 kg, 182
      cm) for 1 h before and 4 h during intravenous (iv) fructose administration (20%
      at 50 mumol.kg-1.min-1) with (+P) or without (-P) propranolol (100 micrograms/kg,
      1 microgram.kg-1.min-1) during the last 2 h. Some subjects were studied a further
      2 h with fructose infusion and +P or -P in hyperinsulinemic (2.9 pmol.kg-1.min-1)
      euglycemic conditions. Glucose turnover ([3-3H]glucose, 20 muCi bolus and 0.2
      muCi/min) was calculated over 30 min at 0, 2, 4, and 6 h. The thermic effect of
      iv fructose was approximately 7.5% and decreased to 4.9 +/- 0.4% (P less than
      0.01) +P. During the euglycemic clamp the thermic effect was 6.2 +/- 0.9% (-P)
      and 5.3 +/- 0.9% (+P). Hepatic glucose production (HGP) was 11.7 mumol.kg-1.min-1
      (0 h) and did not change after 2 h iv fructose (11.8 +/- 0.5 and 9.8 +/- 0.6
      mumol.kg-1.min-1 -P and +P, respectively) but increased to 13.8 +/- 0.9 (-P) and
      12.9 +/- 0.8 mumol.kg-1.min-1 (+P) (P less than 0.01) after 4 h. HGP was
      suppressed to varying degrees during the euglycemic clamp. It is concluded that
      1) the greater thermic effect of fructose compared with glucose is probably due
      to continued gluconeogenesis (which is suppressed by glucose or glucose-insulin)
      and the energy cost of fructose metabolism to glucose in the liver. 2) There is a
      sympathetically mediated component to the thermic effect of fructose
      (approximately 30%) that is not mediated by elevated plasma insulin
      concentrations similar to those observed with iv glucose.

PMID- 1350421
TI  - Role of transglutaminase and protein cross-linking in the repair of mucosal
      stress erosions.
AB  - We have recently demonstrated that polyamines are absolutely required for gastric
      and duodenal mucosal repair after stress. Polyamines act as substrates for
      transglutaminase and facilitate protein cross-linking. The current study tests
      whether transglutaminase and protein cross-linking are involved in the mechanism
      of mucosal healing. Rats were fasted 22 h, placed in restraint cages, and
      immersed in water to the xiphoid process for 6 h. Animals were killed immediately
      or 4, 12, or 24 h after stress. Gastric and duodenal mucosa were examined
      histologically and grossly, and transglutaminase activity was measured.
      Transglutaminase activity in gastric and duodenal mucosa was increased
      significantly from 0 to 8 h, peaking 4 h after the 6-h stress period. By 12 h,
      enzyme activity in duodenal mucosa had returned to control values while gastric
      mucosal transglutaminase did not decrease to control values until 24 h. Mucosal
      recovery from lesions produced by stress was evident 12 h after stress and was
      almost complete by 24 h. Dansylcadaverine (100 mg/kg, orally), a specific
      inhibitor of protein cross-linking, not only prevented the increases in
      transglutaminase but significantly decreased healing in both tissues. Oral
      administration of the polyamine spermidine (100 mg/kg) immediately after stress
      totally prevented inhibition of repair caused by blocking ornithine decarboxylase
      with difluoromethylornithine (DFMO, 500 mg/kg). Administration of
      dansylcadaverine, together with spermidine, significantly prevented the
      beneficial effect of spermidine on mucosal healing in the DFMO-treated
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350422
TI  - Granulocyte accumulation in postischemic intestine: role of leukocyte adhesion
      glycoprotein CD11/CD18.
AB  - Neutrophils play an important role in ischemia-reperfusion (I/R)-induced vascular
      injury in the small intestine. Monoclonal antibodies against the leukocyte
      adhesion glycoprotein CD11/CD18 afford protection against I/R-induced
      microvascular injury. It has been suggested that the response to I/R differs
      between the various layers of the bowel wall, with relatively few granulocytes
      accumulating in the mucosa compared with the serosa or mesentery. The objectives
      of this study were to determine whether I/R-induced neutrophil accumulation is 1)
      homogenous in the different layers of intestine (mucosa, submucosa, muscle, and
      mesentery) and 2) dependent on the expression and/or activation of the leukocyte
      adhesion glycoprotein CD11/CD18. Neutrophil infiltration was monitored by
      measuring myeloperoxidase activity in mucosa, submucosa, muscle, and mesentery of
      cat small intestine subjected to 3 h ischemia (blood flow reduced to 20% of
      control) and reperfusion. I/R elicited a comparable degree of polymorphonuclear
      (PMN) infiltration in mucosa, submucosa, and mesentery, with the muscularis
      exhibiting a greater response. Pretreatment with the CD18-specific monoclonal
      antibody (IB4) significantly attenuated the I/R-induced PMN accumulation in all
      layers of the bowel wall and mesentery, indicating that the granulocyte
      accumulation elicited by I/R is dependent on the expression and/or activation of
      the leukocyte adhesion molecule CD11/CD18.

PMID- 1350423
TI  - Effects of histamine on guinea pig nasal mucosal secretion.
AB  - A guinea pig model of nasal secretory responses was developed to assess the
      contributions of vascular permeability and glandular secretion in the production
      of nasal secretions. The secretory responses to saline, histamine,
      chlorpheniramine (H1-antagonist), cimetidine (H2 antagonist), and atropine
      (muscarinic antagonist) on ipsilateral and contralateral (reflex) secretory
      responses were analyzed by measurement of total protein (Lowry method), 125I
      labeled bovine serum albumin (125I-BSA; administered intravenously) and guinea
      pig albumin (measured by enzyme-linked immunoabsorbent assay) in nasal
      secretions. Significant, dose-dependent secretion of total protein, 125I-BSA, and
      albumin occurred after histamine provocation on the ipsilateral challenged
      nostril and at several doses on the contralateral (unchallenged) nostril.
      Histamine-induced total protein and albumin secretion were blocked by
      chlorpheniramine but not cimetidine. Atropine pretreatment partially reduced
      total protein secretion. Guinea pig albumin immunoreactive material was detected
      by immunohistochemistry in superficial vessels, interstitial areas, the
      epithelium, between glandular cells of submucosal glands, and in gland lumens.
      Approximately 10% of submucosal gland cells contained albumin immunoreactive
      material in their cytoplasm. Autoradiography demonstrated that intravenously
      injected 125I-BSA moved quickly into extracellular areas and then to the
      epithelium and glands. These observations suggest that histamine stimulates
      vascular permeability, glandular secretion, and sensory nerve stimulation and
      that the ipsilateral and contralateral glandular secretion was at least partly
      due to an atropine-inhibitable cholinergic reflex.

PMID- 1350424
TI  - Exogenous glutathione protects endothelial cells from menadione toxicity.
AB  - Administration of menadione (vitamin K3; 2-methyl-1,4-naphthoquinone) to cultured
      bovine pulmonary artery endothelial cells caused a dose- and time-dependent
      depletion of cellular ATP and depletion of intracellular glutathione (GSH). The
      toxicity of menadione was correlated with an increase of menadione-glutathione
      conjugate in the medium and with an increase in H2O2 generation. Recent studies
      have suggested that GSH may be useful as a pharmacological agent to prevent
      oxidant injury. In the present study, treatment with exogenous GSH prevented the
      loss of cellular GSH and ATP caused by menadione. Protection by extracellular GSH
      involved two mechanisms. In one mechanism, extracellular GSH was degraded by
      gamma-glutamyl transpeptidase, producing substrates for subsequent intracellular
      de novo GSH synthesis. We found that the protective effect of extracellular GSH
      was decreased by inhibiting gamma-glutamyl transpeptidase. In the other
      mechanism, GSH reacted in the medium with menadione to form a conjugate. Although
      formation of the menadione-glutathione conjugate within cells may contribute to
      menadione toxicity, addition of menadione-glutathione conjugate to the medium was
      found to be nontoxic to endothelial cells. Thus exogenous GSH protected
      endothelial cells by two mechanisms: maintenance of intracellular GSH and
      prevention of menadione entrance into cells.

PMID- 1350425
TI  - Burn-induced alterations in cardiac beta-adrenergic receptors.
AB  - Previous studies in our laboratory have demonstrated that burn injury (45% total
      body surface area, 3rd-degree scald burn) diminishes contractile and relaxation
      function in the isolated perfused guinea pig heart. The mechanisms responsible
      for the burn-mediated dysfunction are not well understood. Therefore the purpose
      of this study was to examine the inotropic response to isoproterenol, a beta
      adrenergic agonist, and burn-induced alterations in beta-adrenergic receptors
      (beta-AR) in adult guinea pig hearts. Isoproterenol dose-response curves were
      generated in isolated perfused hearts from sham-burned and burned guinea pigs. In
      addition, binding studies were performed using [125I]iodocyanopindolol on hearts
      from sham-burned and burned guinea pigs. Both the functional response and
      sensitivity to isoproterenol were significantly diminished 24 h after burn
      injury. beta-AR density (binding capacity, Bmax) and affinity were determined by
      Scatchard analysis. Agonist competition curves were performed in the presence or
      absence of 0.1 mM 5'-guanylyl imidodiphosphate. There was no difference in Bmax
      in membranes from sham-burned and burned hearts; however, the affinity of beta-AR
      was significantly decreased after burn injury compared with sham burn
      [dissociation constant = 32.5 +/- 1.9 (mean +/- SE), n = 10, vs. 26.7 +/- 1.7 pM,
      n = 10, P = 0.039]. Furthermore, the fraction of receptors in a high-affinity
      state (those functionally coupled to Gs protein) was significantly decreased
      after burn injury compared with sham burn (41.2 +/- 4.7%, n = 9, vs. 54 +/- 2%, n
      = 9, P = 0.023).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350426
TI  - Neurogenic vasodilator control of rabbit ear blood flow.
AB  - Ear blood flow subserves thermoregulation in the rabbit. The purpose of this
      study was to determine if the increase in rabbit ear blood flow, in response to
      increases in internal temperature (Ti) of approximately 2 degrees C (38.0-40.0
      degrees C), is due to an active vasodilation or a withdrawal of adrenergic
      vasoconstrictor activity. New Zealand White rabbits were chronically instrumented
      with a pulse Doppler flow probe on the central ear artery of the left and right
      ear for the measurement of ear blood flow velocity (EBF, kHz). Catheters were
      also positioned in one occipital artery for selective administration of an alpha
      1-adrenergic antagonist to one ear, while the contralateral ear served as a
      control. During hyperthermia (H) (increase in rectal temperature) alpha 1
      adrenergic blockade had no effect on the maximum EBF (5.95 +/- 0.87 before vs.
      6.11 +/- 1.04 kHz after). However, alpha 1-adrenergic blockade increased resting
      EBF during normothermia from 0.18 +/- 0.04 to 1.23 +/- 0.27 kHz (P less than
      0.05), suggesting that a decrease in alpha 1-adrenergic tone may account for
      approximately 20% of the increase in EBF during heating. The second protocol was
      designed to determine if blockade of the auricular nerve would alter EBF response
      to H. During maximum EBF during H, saline or procainamide was injected in the
      tissue surrounding the auricular nerve. Injection of procainamide decreased EBF
      from 5.99 +/- 0.87 to 0.48 +/- 0.19 kHz, while injection of saline had no effect
      on EBF of the contralateral ear (4.33 +/- 1.16 before vs. 3.97 +/- 1.04 kHz
      after).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350427
TI  - G proteins: implications for psychiatry.
AB  - There is mounting evidence that a family of guanosine triphosphate binding
      proteins (G proteins) play an obligatory role in the transduction of a vast array
      of extracellular, receptor-detected signals across cell membranes to
      intracellular effectors. The author reviews the literature dealing with G protein
      coupling to second messenger generation, the role of G proteins in regulating
      both the convergence and divergence of neurotransmitter action in the CNS, and
      the involvement of G proteins in a variety of clinical conditions, with an
      emphasis on psychiatric conditions and their treatments. G proteins from the
      basis of signal integration in the CNS, endowing the neuron with a large degree
      of functional diversity. Abnormalities in the function and/or expression of G
      proteins have been implicated in a variety of pathophysiologic states, and a
      number of currently available psychotropic drugs affect G proteins. The
      understanding of the mechanisms by which G proteins modulate neuronal activity
      may be one of the keys to understanding the functioning and the complexities of
      the nervous system. Given their widespread, critical roles in the regulation of
      neuronal function, it seems likely that G proteins are involved in the
      pathophysiology of various major psychiatric illnesses. The development of novel,
      site-specific drugs with primary G protein targets remains an exciting prospect
      for the future.

PMID- 1350429
TI  - Patients' opinions concerning side effects of depot neuroleptics.

PMID- 1350428
TI  - Treatment of tardive dyskinesia with vitamin E.
AB  - OBJECTIVE: Vitamin E (alpha-tocopherol), a free-radical scavenger, has been
      reported to improve symptoms of tardive dyskinesia. The authors attempted to
      replicate this finding under more controlled conditions in a larger study group.
      METHOD: Fifteen inpatients and six outpatients with tardive dyskinesia received
      up to 1600 IU/day of vitamin E for 6 weeks in a double-blind, placebo-controlled
      crossover study. Abnormal Involuntary Movement Scale (AIMS) examinations of these
      patients were videotaped and rated independently by two trained raters. Levels of
      neuroleptic medication and vitamin E were measured during both treatment periods.
      Eighteen patients who demonstrated high blood levels of vitamin E were included
      in the data analysis. RESULTS: Vitamin E levels were significantly higher while
      the patients were receiving vitamin E than while they were receiving placebo. For
      all 18 patients, there were no significant differences between AIMS scores after
      receiving vitamin E and AIMS scores after receiving placebo. In agreement with
      previous studies, however, the nine patients who had had tardive dyskinesia for 5
      years or less had significantly lower AIMS scores after receiving vitamin E than
      after receiving placebo. There were no changes in neuroleptic levels during
      vitamin E treatment. CONCLUSIONS: Vitamin E had a minor beneficial effect on
      tardive dyskinesia ratings in a selected group of patients who had had tardive
      dyskinesia for 5 years or less. This effect was not due to an increase in blood
      levels of neuroleptic medications.

PMID- 1350430
TI  - Phencyclidine and schizophrenia.

PMID- 1350431
TI  - Symposium on life transitions and alcohol consumption: work-related issues.

PMID- 1350432
TI  - [Development of continuous monitoring of spontaneous respiration in the
      postoperative phase. 2. Cutaneous oxygen and carbon dioxide partial pressures
      following i.v. bolus application of fentanyl, buprenorphine, naloxone and
      amiphenazole in healthy adult subjects].
AB  - METHODS: In an attempt to develop a noninvasive monitoring technique for patients
      in the early postoperative period, cutaneous O2 and CO2 pressures (pctO2, pctCO2)
      were monitored in ten healthy adult volunteers of both sexes (5 male, 5 female,
      age 29 +/- 5 years, weight 68 +/- 11 kg) who received, in several sessions after
      a 60-min equilibration period, i.v. bolus doses of fentanyl (3 micrograms/kg and,
      60 min later, another 1.5 micrograms/kg), buprenorphine (3 and 1.5
      micrograms/kg), naloxone (1.8 and 0.9 micrograms/kg), and the respiratory
      analeptic amiphenazole (2 and 1 mg/kg) as well as combinations of
      fentanyl/amiphenazole or buprenorphine/naloxone in the aforementioned dosages.
      Data were collected and stored by a personal computer using the TCM3 system with
      a combination electrode for simultaneous measuring of pctO2 and pctCO2 (TINA,
      Radiometer) at 30-s intervals. The overall observation period was 240 min. Means,
      standard deviations, and ranges were calculated for individual data and data
      pooled for 15-min intervals. Groups were compared by means of Student's t-test
      and analysis of variance. RESULTS: Following i.v. fentanyl 3 micrograms/kg, pctO2
      decreased and pctCO2 increased rapidly and statistically significantly. The
      changes were of similar intensity after the first and second doses (1.5
      micrograms/kg) and normalized about 60 min after each injection. In contrast,
      following i.v. buprenorphine (3 and 1.5 micrograms/kg) the cutaneous partial
      pressures changed continuously and progressively during the observation period
      and did not reach the control values after 240 min. Naloxone and amiphenazole
      injections had no obvious influence on the time course of the blood gas tensions.
      If opiates and antagonists were combined, neither the fentanyl/amiphenazole group
      nor the buprenorphine/naloxone group differed significantly from the respective
      opiate groups. DISCUSSION AND CONCLUSION: As was discussed in detail in a
      previous communication, monitoring of opiate-induced respiratory depression must
      be nonstimulant and, preferably, noninvasive. Whereas the precision and/or
      limitations of monitoring partial oxygen saturations by pulse oximetry is well
      documented in the literature, knowledge of the value of cutaneous partial
      pressure monitoring is still limited and controversial for the adult patient
      population. The present study was performed to define the usefulness of cutaneous
      blood gas analysis in healthy volunteers receiving opiate dosages well known in
      recovery room patients. It is concluded that continuous monitoring of pctO2 and
      pctCO2 can indeed detect opiate-induced respiratory depression in adults. The
      well-known difference in respiratory pattern for fentanyl and buprenorphine could
      easily be determined. It was confirmed that naloxone and amiphenazole in the
      dosage range studied do not influence spontaneous respiration in healthy adults.
      Thus, the authors are convinced that continuous monitoring of cutaneous partial
      pressures of oxygen and carbon dioxide is sensitive enough to be used, in
      combination with pulse oximetry, in a monitoring concept for patients recovering
      from surgery and anaesthesia. Results in patients undergoing conventional pain
      management or patient-controlled analgesia with relatively high opiate dosages
      will be presented in following papers. Concerning the controversy about
      clinically relevant interactions between fentanyl and amiphenazole or
      buprenorphine and naloxone, the present study did not confirm any useful
      antagonism. Whether this is due to limitations of cutaneous monitoring, the
      difference between volunteers and patients, or pharmacological reasons must be
      evaluated in further investigations.

PMID- 1350433
TI  - Dual-enzyme fiber-optic biosensor for glutamate based on reduced nicotinamide
      adenine dinucleotide luminescence.
AB  - Response characteristics are presented for a dual-enzyme fiber-optic biosensor
      for glutamate. An enzyme layer composed of glutamate dehydrogenase (GDH) and
      glutamate-pyruvate transaminase (GPT) is used to produce reduced nicotinamide
      adenine dinucleotide (NADH) at the tip of a fiber-optic probe. NADH luminescence
      is monitored through this probe and the measured fluorescence intensity is
      related to the concentration of glutamate. GDH catalyzes the formation of NADH,
      and GPT drives the GDH reaction by removing a reaction product and regenerating
      glutamate. Optimal response is obtained in a pH 7.4 Tris-HCl buffer maintained at
      25 degrees C in the presence of 4 mM NAD+ and 10 mM L-alanine. The temperature
      profile reveals a strong negative temperature effect which is attributed to the
      temperature dependency of NADH luminescence. Under optimal conditions, the sensor
      sensitivity is 0.127 nA/microM over the 1-10 microM concentration range, the
      detection limit is 0.13 microM, and response times range from 4 to 8 min. The
      sensor response is stable for 12 days when stored at 4 degrees C. Selectivity for
      glutamate is excellent over most of the common amino acids as well as ascorbic
      acid, uric acid, taurine, and GABA. Only slight responses were observed for
      glutamine and lysine. The effect of ammonia on the glutamate response was found
      to be minimal at total ammonia nitrogen concentrations as high as 200 microM.

PMID- 1350434
TI  - APIC '92: Nineteenth Annual Conference and International Meeting. San Francisco,
      California, May 31-June 4, 1992. Abstracts.

PMID- 1350436
TI  - Transglutaminase catalyses the modification of glutamine side chains in the C
      terminal region of bovine beta-lactoglobulin.
AB  - The transglutaminase-catalysed incorporation of primary amines (putrescine and
      monodansylcadaverine) into bovine beta-lactoglobulin has been studied. In the
      presence of 1 mM-dithiothreitol between 1 and 2 mol of amine can be incorporated
      per mol of beta-lactoglobulin subunit. There is very little incorporation of
      amines in the absence of reducing agent. By isolating and sequencing the modified
      peptides, the sites of modification have been identified as Gln-159 (preferred)
      and Gln-155. C.d. has been used to study the structure of beta-lactoglobulin over
      a range of pH values and in the presence or absence of dithiothreitol. The
      results are discussed in terms of the X-ray-crystallographically determined
      structure of beta-lactoglobulin.

PMID- 1350435
TI  - Nucleotide regulation of heat-stable enterotoxin receptor binding and of
      guanylate cyclase activation.
AB  - Certain nucleotides were found to regulate the binding of the Escherichia coli
      heat-stable enterotoxin (STa) to its receptor in pig intestinal brush border
      membranes. ATP and adenine nucleotide analogues inhibited 125I-STa binding, while
      guanine nucleotide analogues stimulated binding, with maximal effects at 0.5-1.0
      mM. The strongest inhibitors were adenosine 5'-[beta gamma-imido]triphosphate
      (App[NH]p) (36%) and adenosine 5'-[beta-thio]diphosphate (ADP[S]) (41%).
      Inhibition did not require Mg2+, and was blocked by p
      chloromercuribenzenesulphonate (PCMBS). Stimulation of binding required Mg2+, was
      not prevented by PCMBS and was maximal with GDP[S] (41%). While App[NH]p and
      MgGDP[S] appeared to be acting at different sites, they also interfered with each
      other. These nucleotides exerted only inhibitory effects on STa-stimulated
      guanylate cyclase activity, in contrast with the stimulatory effects of adenine
      nucleotides on atrial natriuretic peptide (ANP)-stimulated guanylate cyclase.
      Inhibition by low concentrations of MgApp[NH]p and MgATP was weaker above 0.1 mM,
      while MgGDP[S] and magnesium guanosine 5'-[gamma-thio]triphosphate (MgGTP[S])
      inhibited in a single phase. Inhibition by MgApp[NH]p, at all concentrations, was
      competitive with the substrate (MgGTP), as was that by MgGDP[S] and MgGTP[S].
      Whereas membrane guanylate cyclases usually show positively co-operative kinetics
      with respect to the substrate, STa-stimulated activity exhibited Michaelis-Menten
      kinetics with respect to MgGTP. This changed to positive co-operativity when
      Lubrol PX was the activator, or when the substrate was MnGTP. These results
      suggest the presence of both a regulatory and a catalytic nucleotide-binding
      site, which do not interact co-operatively with STa activation.

PMID- 1350437
TI  - Expression of Ca2+ receptors in Xenopus oocytes injected with poly(A)+ mRNA from
      a rat calcitonin-secreting cell line.
AB  - Poly(A)+ mRNA extracted from rat calcitonin-secreting cells (rMTC 44-2) was
      injected into Xenopus oocytes. In mRNA-injected oocytes the intracellular Ca2+
      concentration ([Ca2+]i), measured with the Ca2+ indicator dye, fura2, increased
      in response to an elevation of the extracellular Ca2+ ions ([Ca2+]o). In some
      oocytes [Ca2+]i transiently increased in high [Ca2+]o but it did not respond to
      the subsequent alterations of [Ca2+]o. The addition of 10 microM carbonyl cyanide
      m-chlorphenylhydrazone (CCCP) to the extracellular medium restored the dependence
      of [Ca2+]i on [Ca2+]o in such cells. It was concluded that rMTC 44-2 cells
      possessed a receptor which recognizes changes in [Ca2+]o and that these receptors
      can be functionally expressed by microinjection of messenger RNA from rMTC 44-2
      cells into Xenopus oocytes.

PMID- 1350439
TI  - Guidelines for meeting the communication needs of persons with severe
      disabilities. National Joint Committee for the Communicative Needs of Persons
      with Severe Disabilities.
AB  - In summary, the current best practices in the facilitation and enhancement of
      communication among persons with severe disabilities reflect six major tenets:
      (a) communication is social behavior; (b) effective communicative acts can be
      produced in a variety of modes; (c) appropriate communicative functions are those
      that are useful in enabling individuals with disabilities to participate
      productively in interactions with other people; (d) effective intervention must
      also include efforts to modify the physical and social elements of environments
      in ways that ensure that these environments will invite, accept, and respond to
      the communicative acts of persons with severe disabilities; (e) effective
      intervention must fully utilize the naturally occurring interactive contexts
      (e.g., educational, living, leisure, and work) that are experienced by persons
      with severe disabilities; and (f) service delivery must involve family members or
      guardians and professional and paraprofessional personnel. These six tenets have
      resulted in assessment, intervention, and service delivery models that offer
      maximum responsiveness to the need to establish communicative repertoires that
      will allow persons with severe disabilities to function effectively in least
      restrictive environments--in productive interactions with others.

PMID- 1350438
TI  - Familial adenomatous polyposis: identification of a new frameshift mutation of
      the APC gene in an Italian family.
AB  - Familial Adenomatous Polyposis (FAP) is a premalignant disease of the
      gastrointestinal tract inherited as an autosomal dominant trait assigned to
      chromosome 5q21. The 15 exons of the APC gene responsible for the defect were
      amplified from the DNA of one FAP patient. SSCP analysis of the amplified DNA
      revealed a variant conformer of exon 10. The sequencing of the cloned PCR product
      showed a 1 base insertion at position 1370, creating a stop codon four
      nucleotides downstream. SSCP analysis of 20 family members and nucleotide
      sequencing of exon 10 in three affected members confirmed the Mendelian
      inheritance of the mutant allele.

PMID- 1350441
TI  - Evaluation and treatment for tracheoesophageal fistulization/puncture. Ad Hoc
      Committee on Advances in Clinical Practice. American Speech-Language-Hearing
      Association.

PMID- 1350440
TI  - Electrical stimulation for cochlear implant selection and rehabilitation. Ad Hoc
      Committee on Advances in Clinical Practice. American Speech-Language-Hearing
      Association.

PMID- 1350442
TI  - External auditory canal examination and cerumen management. Ad Hoc Committee on
      Advances in Clinical Practice. American Speech-Language-Hearing Association.

PMID- 1350443
TI  - Instrumental diagnostic procedures for swallowing. Ad Hoc Committee on Advances
      in Clinical Practice. American Speech-Language-Hearing Association.

PMID- 1350444
TI  - Neurophysiologic intraoperative monitoring. Ad Hoc Committee on Advances in
      Clinical Practice. American Speech-Language-Hearing Association.

PMID- 1350445
TI  - Vocal tract visualization and imaging. Ad Hoc Committee on Advances in Clinical
      Practice. American Speech-Language-Hearing Association.

PMID- 1350446
TI  - Sedation and topical anesthetics in audiology and speech-language pathology. Ad
      Hoc Committee on Advances in Clinical Practice. American Speech-Language-Hearing
      Association.
AB  - Audiologists and speech-language pathologists who participate in or perform
      procedures on patients who have been medicated for sedation or topical anesthesia
      should appreciate the complex factors which may expose their patients to risk or
      harm. Administration of medications to achieve a desired patient state is a
      medical procedure requiring physician or dentist prescription, physician or
      dentist approval on the conditions of administration and monitoring, and
      physician or dentist availability for provision of emergency care that may be
      required. For these reasons, audiologists and speech-language pathologists should
      address issues of scope of practice as defined by state licensing boards and
      institutional regulatory committees, professional liability, and patient and
      practitioner safety before engaging in procedures on individuals medicated for
      sedation or topical anesthesia. These issues should be defined in specific,
      written protocols that the audiologist and speech-language pathologist develop in
      collaboration with physicians, dentists, and other medical professionals who are
      responsible for patient care. The protocols should specify responsibility for
      each aspect of care and limit procedures to professional settings with immediate
      access to emergency medical care. In all instances, both in development of
      written protocols and in actual professional practice, the comfort and safety of
      the patient must be paramount.

PMID- 1350447
TI  - Balance system assessment. Ad Hoc Committee on Advances in Clinical Practice.
      American Speech-Language-Hearing Association.

PMID- 1350448
TI  - Analgesia induced by electroacupuncture of different frequencies is mediated by
      different types of opioid receptors: another cross-tolerance study.
AB  - The cross-tolerance technique was used to analyze the receptor mechanisms of
      analgesia induced by electroacupuncture (EA) of 2 Hz, 100 Hz, or 2-15 Hz. (1)
      Rats were given EA stimulation of 2 Hz, 100 Hz and 2-15 Hz for 30 min with 30 min
      intervals successively. The percentage increase in tail-flick latency (TFL) was
      taken to indicate the intensity of EA analgesia. Rats made tolerant to repeated
      intrathecal injection of the mu-opioid agonist ohmefentanyl (OMF, 15 pmol, Q2h x
      5) or the delta-opioid agonist DPDPE (10 nmol, Q2h x 5) showed a cross tolerance
      to both 2 Hz- and 2-15 Hz-, but not to 100 Hz-EA analgesia; and rats made
      tolerant to kappa-opioid agonist dynorphin-(1-13) (5 nmol, Q2h x 5) showed a
      cross-tolerance to 100 Hz- and 2-15 Hz-, but not to 2 Hz-EA analgesia; (2) Rats
      made tolerant to 2-15 Hz EA showed cross-tolerance to either 2 Hz- or 100 Hz-EA
      analgesia; (3) Rats made tolerant to either 2 Hz- or 100 Hz-EA were still
      reactive to 2-15 Hz-EA. The results indicate that 2 Hz-EA analgesia is mediated
      by mu- and delta-receptors, 100 Hz-EA analgesia by kappa-receptor, and 2-15 Hz-EA
      analgesia by combined action of mu-, delta- and kappa-receptors in the spinal
      cord of the rats.

PMID- 1350449
TI  - Effects of intraventricular infusion of the N-methyl-D-aspartate (NMDA) receptor
      antagonist AP5 on spatial memory of rats in a radial arm maze.
AB  - Rats were trained to asymptotic performance in an 8-arm radial maze. They then
      received chronic intraventricular infusion of either artificial CSF or the N
      methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5- phosphonopentanoic
      acid (AP5), at a concentration (30 mM) that has been shown previously to prevent
      the induction of long-term potentiation in the dentate gyrus of the hippocampus
      in vivo. Subsequently the rats received another 9 trials in the maze in a quasi
      random order, 3 uninterrupted trials, and another 6 trials each with mid-trial
      delays of 5, 20 or 60 min during which the animals were placed in their home
      cage. The mean number of errors for the AP5 rats did not differ significantly
      from that of the controls in the uninterrupted trials throughout the experiment,
      nor did it differ from that of the controls in any of the 3 delayed trials when
      these were first introduced. However, the control animals performed better at the
      longer delays when these were introduced for the second time, whilst there was no
      such improvement (but rather a deterioration) for the AP5 animals. The impairment
      of performance in the AP5 rats during the second block of delayed trials was
      significant, and independent of the length of the delay. These results show that
      NMDA receptor blockade does not impair working memory in the radial maze per se,
      but that it does prevent an improvement of working memory persistence with
      further training.

PMID- 1350450
TI  - N-methyl-D-aspartate antagonist D-APV selectively disrupts taste-potentiated odor
      aversion learning.
AB  - Two experiments examined the effects of the competitive N-methyl-D-aspartate
      (NMDA) antagonist D-APV (D-2-amino-5-phosphonovalerate) on rats' ability to
      acquire potentiated aversions to the odor element of a taste-odor compound. In
      Experiment 1, pretreatment with D-APV (2.5 micrograms/side icv) caused
      stereospecific deficits in potentiated odor aversion learning but left simple
      taste and odor aversion learning intact. In Experiment 2, pretreatment with D-APV
      had no effect on rats' acquisition of an illness-based odor discrimination task.
      These results parallel those previously obtained using a noncompetitive NMDA
      antagonist (Robinson, Crooks, Shinkman, & Gallagher, 1989) and show that
      interference with NMDA receptors can selectively impair potentiated odor aversion
      learning. These results suggest that NMDA receptors play a critical role in some,
      but not all, forms of learning and memory.

PMID- 1350451
TI  - Altered expression of NGF and P75 NGF-receptor by fibroblasts of injured teeth
      precedes sensory nerve sprouting.
AB  - Profuse sprouting of sensory nerve fibers occurs in tooth pulp by 1-4 days
      following dentin injury. A possible role for nerve growth factor (NGF) in that
      neural response is suggested here by the demonstration that NGF mRNA and protein
      are increased 6 hr after injury to adult rat molars. The enhanced expression of
      NGF mRNA was localized to fibroblasts underlying the injury. A concomitant
      depletion of mRNA encoding the 75 Kd NGF receptor (NGFR) was observed in those
      fibroblasts. The increase in NGF mRNA was transitory and mRNA levels fell below
      normal levels by 2 days after injury. Both NGF and NGFR mRNA remained low
      thereafter in injured pulp. The inverse shifts in fibroblastic mRNA encoding NGF
      and NGFR were not affected by prior denervation of the tissue, or by pretreatment
      with dexamethasone. The regulatory mechanisms therefore must involve endogenous,
      non-neuronal, non-inflammatory factors that are released in response to injury.

PMID- 1350452
TI  - Tamoxifen up-regulates c-erbB-2 expression in oestrogen-responsive breast cancer
      cells in vitro.
AB  - Expression of the c-erbB-2 proto-oncogene is inhibited by oestrogens in oestrogen
      responsive human breast cancer cells, at both mRNA and protein level. Here we
      report that, where the regulation of c-erbB-2 is concerned, tamoxifen displays a
      full anti-oestrogenic activity, enhancing the expression of c-erbB-2 in oestrogen
      receptor-positive cells cultured with untreated fetal calf serum or reversing the
      inhibitory effect of added oestrogens. Meanwhile, tamoxifen strongly inhibited
      cell growth. Tamoxifen was inactive on both c-erbB-2 expression and growth of
      oestrogen receptor-negative cells. These results may have important implications
      to explain occasional failure of tamoxifen therapy in oestrogen receptor-positive
      breast cancers.

PMID- 1350453
TI  - Detection of the HER-2/neu proto-oncogene protein p185erbB2 by a novel monoclonal
      antibody (MAB-145ww) in breast cancer membranes from oestrogen and progesterone
      receptor assays.
AB  - Amplification of the proto-oncogene HER-2/neu and/or overexpression of the
      transmembrane protein p185erbB2 that it encodes occur in approximately 30% of
      human breast and gynaecological cancers seen clinically and are strongly
      associated with an unfavourable outcome. We report on the use of a new monoclonal
      antibody (Mab-145ww) together with immunoblotting for detection of p185erbB2 in
      membranes that remain after routine processing of breast cancer tissue for
      steroid receptor assays. Human breast cancer cell lines SKBR3 and MCF-7 were used
      as high and low controls, respectively, for p185erbB2 expression. Mab-145ww was
      detected p185erbB2 in more than half of the breast cancer specimens; the
      expression was intense in SKBR3 cells, but only faint in MCF-7 cells. These
      results demonstrate that routine processing of cancer tissue for steroid receptor
      status can include providing a preparation with which to assess p185erbB2
      expression and, thus, can provide information potentially useful for the clinical
      management of individual cancer patients.

PMID- 1350454
TI  - Calcitonin and PDN-21 as tumour markers in MEN-2 family screening for medullary
      thyroid carcinoma.
AB  - Calcitonin is expressed in medullary thyroid carcinomas (MTC). It is processed
      from a large molecular weight precursor and is flanked at its C-terminal end by a
      21 aminoacid peptide (PDN-21) formed in equimolar concentrations to calcitonin by
      enzymatic cleavage of the prohormone. This investigation compared basal
      measurements of calcitonin and PDN-21 and the response of the two peptides
      following pentagastrin stimulation in normal controls and in family members with
      C-cell hyperplasia or early neoplasia. The results showed that calcitonin and PDN
      21 may both be used in family screening for the MEN-2 syndrome, but the
      unstimulated circulating concentrations of calcitonin were higher and more
      influenced by C-cell hypersecretion than PDN-21 (P less than 0.01), and the
      increase in stimulated concentrations of calcitonin were significantly higher
      than for PDN-21 (P less than 0.01). These findings may be explained by
      differences with respect to secretion and metabolic clearance rate for the two
      peptides.

PMID- 1350455
TI  - Progress in molecular biology of breast cancer.

PMID- 1350456
TI  - Overexpression of the c-erbB-2 oncoprotein: why does this occur more frequently
      in ductal carcinoma in situ than in invasive mammary carcinoma and is this of
      prognostic significance?
AB  - Overexpression of c-erbB-2 occurs in 60% of in situ and 25% of infiltrating
      ductal carcinomas. We have previously found very strong associations between
      immunohistochemical staining for c-erbB-2 and histological pattern and nuclear
      size in ductal carcinoma in situ (DCIS) and less strong correlation with
      proliferative activity. In a further study of infiltrating ductal carcinomas we
      have found that, in addition to tumours arising from c-erbB-2 positive, large
      celled, rapidly proliferating, comedo carcinomas and c-erbB-2 negative small
      celled cribriform/micropapillary carcinomas with a low proliferative rate, there
      is a third group of c-erbB-2 negative tumours with large nuclei and variable
      proliferative activity. These latter tumours are not seen in pure DCIS suggesting
      that they have a very transient in situ stage. Therefore, although in pure DCIS c
      erbB-2 positively appears to be associated with tumours with a greater invasive
      potential, and c-erbB-2 negativity with tumours having a more favourable
      prognosis, the latter is not necessarily true in infiltrating disease.

PMID- 1350457
TI  - Prevalence of amplification of the oncogenes c-myc, HER2/neu, and int-2 in one
      thousand human breast tumours: correlation with steroid receptors.
AB  - The frequency of oncogene amplification described in the literature shows a large
      fluctuation, which could be attributed to the study of relatively small series of
      tumours, to selection of subgroups of patients, or, especially in retrospective
      studies, to selection of tumour material from the tumour-bank. To address this
      question, we have studied amplification of c-myc, HER2/neu and int-2/bcl-1 genes
      in a series of 1052 collected human breast tumours. The retrospective and
      prospective subgroups in this collected series of tumours were of equal size. c
      myc was amplified in 17.1%, HER2/neu in 18.7% and int-2/bcl-1 in 14.1%, of all
      breast cancer specimens studied. In the retrospective subgroup the prevalence of
      amplification was 18.1% for c-myc; 22.6% for HER2/neu and 11.6% for int-2/bcl-1,
      whereas in the prospective subgroup an incidence of amplification of 16.1%, 15.1%
      and 16.3% for c-myc, HER2/neu and int-2/bcl-1, respectively was observed.
      HER2/neu amplification was negatively correlated with oestrogen receptor (ER) and
      progesterone receptor (PR) status (P less than 0.0001; for both), c-myc
      amplification was more prevalent in the PR-negative subpopulation (P less than
      0.05) and int-2/bcl-1 amplification was positively correlated with ER status (P
      less than 0.001).

PMID- 1350458
TI  - Expression of c-erbB2, TGF-beta 1 and pS2 genes in primary human breast cancers.
AB  - The presence of c-erbB2, TGF-beta 1 and pS2 mRNAs was examined in primary breast
      tumours. The c-erbB2 mRNA was overexpressed in 34% of the tumours. There was a
      positive, statistically significant correlation between c-erbB2 gene
      overexpression and nodal status. TGF-beta 1 mRNA was detected in 84% of the
      tumours, regardless of their clinical status. When possible, the c-erbB2 and TGF
      beta 1 proteins were identified immunohistochemically on frozen sections from the
      same tumours. For TGF-beta 1, the mRNA and immunohistochemical results were
      divergent in 6 cases, 5 of which did contain clearly detectable mRNA but did not
      stain with the antibody. The pS2 mRNA was detected in 22% of the tumours and in
      the BT474 cell line. There was a significant correlation between the presence of
      pS2 mRNA and of oestrogen receptors. No statistically significant correlation was
      observed between pS2 and TGF-beta 1 genes expression and the clinical parameters
      of the tumours.

PMID- 1350459
TI  - A developmental perspective on the pathology and neurochemistry of the temporal
      lobe in schizophrenia.
AB  - Neuropathological, neuroimaging, clinical and epidemiological evidence suggests
      that many cases of schizophrenia are developmental in origin. Dysplastic changes
      in the medial temporal lobes appear to be of particular importance. However,
      research implicating a neurodevelopmental origin for schizophrenia has proceeded
      largely in isolation from knowledge concerning the neurochemistry of the
      disorder. This paper attempts to integrate these disparate lines of research, and
      examines the role of trophic mechanisms in the formation of the hippocampus.
      Those neurotransmitters which have been most consistently found to be abnormal in
      the temporal lobes of schizophrenics (excitatory amino acids and CCK), are
      involved in the control of hippocampal development. We suggest that these
      neurotransmitter findings are the residue of abnormalities in their role as
      trophic factors in foetal or neonatal life, and that the latter contribute to the
      developmental aberrations considered fundamental to schizophrenia.

PMID- 1350461
TI  - Co-engagement of CD3 with LFA-1 or ICAM-1 adhesion molecules enhances the
      frequency of activation of single murine CD4+ and CD8+ T cells and induces
      synthesis of IL-3 and IFN-gamma but not IL-4 or IL-6.
AB  - Interaction between the cell adhesion molecules lymphocyte function-associated
      antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) augments T cell
      activation by increasing the avidity of T cell/antigen-presenting cell (APC)
      binding. To examine whether LFA-1 and ICAM-1 can also contribute to T cell
      activation in the absence of APCs, single murine CD4+ and CD8+ T cells were
      cultured with IL-2 and immobilized antibodies to CD3, CD4 or CD8, and LFA-1 or
      ICAM-1. The combination of anti-CD3, anti-CD4/CD8, and IL-2 stimulated
      approximately 20% of CD4+ cells and 30% of CD8+ cells to proliferate. Inclusion
      of anti-ICAM-1 antibody increased these frequencies to 30 and 40% respectively.
      Maximum activation frequencies were obtained with the combination of anti-CD3,
      anti-CD4/CD8, and anti-LFA-1 which stimulated cell division by approximately 40%
      of single CD4+ cells and at least 60% of single CD8+ cells. Under these
      conditions, 30-40% of the resultant CD4+ clones and greater than 90% of CD8+
      clones secreted IL-3 and IFN-gamma. In addition to responding at higher
      frequencies that CD4+ cells, CD8+ cells formed larger clones which produced 4
      fold higher levels of both cytokines. Although the expression of IL-2, IL-3, IFN
      gamma, granulocyte-macrophage colony stimulating factor and tumor necrosis factor
      alpha could be detected in CD4+ and CD8+ clones at the mRNA level following
      reverse transcription and polymerase chain reaction amplification, neither the
      secreted nor mRNA expression of IL-4 or IL-6 was detected in any of the tested
      clones. It is concluded that co-stimulation of T cells via LFA-1 or ICAM-1 can
      enhance T cell receptor-dependent activation in the absence of accessory cells
      and that this mode of stimulation leads to the expression of a restricted range
      of cytokine genes.

PMID- 1350460
TI  - Elevated IgG anti-histone antibodies in a subgroup of medicated schizophrenic
      patients.
AB  - A total of 57 schizophrenic patients (of which 17 were first-episode, neuroleptic
      naive) and 76 healthy controls were screened for anti-histone IgG antibodies
      using an enzyme immunoassay (ELISA). All patients had significantly higher anti
      histone antibody titers than controls (t = 3.1, p less than 0.003). Previously
      medicated patients had significantly higher titers than neuroleptic-naive first
      episode patients (t = 2.87, p less than 0.006). This study suggests that
      neuroleptic medications are associated with anti-histone antibodies.

PMID- 1350462
TI  - In utero treatment with monoclonal antibody to IL-2 receptor beta-chain
      completely abrogates development of Thy-1+ dendritic epidermal cells.
AB  - Interleukin-2 (IL-2), a crucial growth factor for mature T lymphocytes, is
      produced in fetal thymus under developmental control, although its biological
      significance remains unclear. We found that the two distinct subunits of the IL-2
      receptor, i.e. the alpha-chain (IL-2R alpha) and the beta-chain (IL-2R beta),
      were expressed in an almost mutually exclusive fashion throughout fetal thymus
      ontogeny, and that the blockade of IL-2R beta, a signal transducing component of
      IL-2R, by administering a neutralizing mAb to IL-2R beta resulted in the complete
      and selective disappearance of Thy-1+ skin dendritic epidermal cells. Development
      of any other T cell subsets was uncompromised. This indicates that IL-2 plays a
      crucial role in the development of fetal V gamma 5+ cells and their descendants.

PMID- 1350463
TI  - Identification of an equivalent to murine Thy-1+ dendritic epidermal cells in the
      rat epidermis.
AB  - In the murine epidermis, there exist Thy-1+ dendritic epidermal cells (Thy
      1+DEC). These cells are Thy-1+, CD45+, CD3+ and asialo GM1+ but CD5-, CD4-, CD8-,
      or Ia-1-, and express T cell receptor (TCR) gamma delta. Recently, most of these
      TCR gamma delta of Thy-1 DEC are shown to consist of a V gamma 3-V delta 1
      combination. There has been no evidence that the same type of cell population
      exists in other species except mice. In this study, we investigated the existence
      of a Thy-1+DEC equivalent in the rat epidermis. The epidermal sheets obtained
      from rats were stained with various monoclonal antibodies to rat lymphocytes. We
      developed a monoclonal antibody (1F4) to rat CD3 complex. 1F4 stained thymocytes
      and peripheral T cells and also immunoprecipitated T cell receptor with CD3
      complex. Using 1F4 and a recently developed monoclonal antibody to rat TCR alpha
      beta, we could identify dendritic CD4-, CD8-, CD5-, CD3+, TCR alpha beta- cells
      in the rat epidermis. These CD3+, TCR alpha beta- cells are strong candidates as
      an equivalent to TCR gamma delta + murine Thy-1+ DEC.

PMID- 1350464
TI  - Relation between 25-hydroxyvitamin D3, apolipoprotein A-I, and high density
      lipoprotein cholesterol.
AB  - In a survey of cardiovascular risk factors in 185 men and 173 women of a Belgian
      population group, an independent and highly significant positive correlation was
      found between the serum concentrations of 25-hydroxyvitamin D3 and apolipoprotein
      A-I (p less than 0.001 in both sexes). 25-Hydroxyvitamin D3 also showed a
      positive correlation with high density lipoprotein cholesterol levels (p less
      than 0.05 in men and p less than 0.005 in women). This relation was independent
      of a possible effect of 25-hydroxyvitamin D3 on serum calcium. Taking the
      biological variation of 25-hydroxyvitamin D3 levels (+/- 2 SD = 25 ng/ml) into
      account, these findings could explain variations in the levels of apolipoprotein
      A-I of 15 mg/100 ml and of high density lipoprotein cholesterol of 4 mg/100 ml.

PMID- 1350465
TI  - A DNA polymorphism for LCAT is associated with altered LCAT activity and high
      density lipoprotein size distributions in baboons.
AB  - A polymorphic Pvu II site was mapped to intron 5 of LCAT, the gene encoding
      baboon lecithin: cholesterol acyltransferase (LCAT). In a study of 83 baboons,
      heterozygous baboons (Pv1/Pv2) had significantly higher LCAT enzyme activity
      levels than did baboons homozygous for the more common allele (Pv1/Pv1). LCAT
      genotype explained 6% of the total variation in LCAT enzyme activity. To test for
      allelic effects on cholesterol metabolism, we compared serum concentrations of
      high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I). We
      also compared distributions of cholesterol and apo A-I among three HDL size
      classes (HDL1, HDL2, and HDL3). All measurements were obtained for each baboon
      after long-term feeding of a basal diet low in cholesterol and fat and again
      after 7 weeks on an atherogenic diet. Heterozygous baboons had significantly
      lower serum levels of total cholesterol than did homozygotes. In addition, we
      detected significant effects of LCAT genotype on size distributions of HDL
      cholesterol and apo A-I on both diets but did not detect any genotype-by-diet
      interaction. Heterozygotes had increased amounts of cholesterol and apo A-I in
      HDL3 particles and lower amounts of cholesterol and apo A-I in the larger HDL
      size classes by comparison with homozygotes. Overall, the LCAT polymorphism
      explained a significant proportion of total variation in cholesterol (4-10%) and
      apo A-I (13%) distributions on both diets. Thus, the results indicate that the
      LCAT polymorphism is associated with significant differences in LCAT enzyme
      activity and with alterations in HDL compositions.

PMID- 1350466
TI  - Alterations in substrate utilization in the reperfused myocardium: a direct
      analysis by 13C NMR.
AB  - An alternative 13C NMR method which allows direct determination of substrate
      oxidation in tissue for up to three competing 13C-enriched substrates is
      presented. Oxidation of competing substrates can be measured by 13C NMR
      spectroscopy under non-steady-state conditions if the relative areas of the
      glutamate C3 and C4 resonances can be determined. The accuracy of this
      measurement is limited during brief exposure to 13C-enriched substrates because
      of the low enrichment in the C3 carbon. The glutamate C4 resonance from a tissue
      sample which has oxidized a combination of [1,2-13C]acetate (or a uniformly
      enriched fatty acid mixture) and [3-13C]lactate appears as a nine-line resonance
      consisting of four multiplet components: a singlet (C4S), two doublets with
      differing one-bond coupling constants (C4D34 and C4D45), and a quartet (C4Q). It
      is shown that the sum of the C4S + C4D34 resonance areas versus the C4D45 + C4Q
      resonance areas directly reports the relative utilization of [3-13C]lactate
      versus [1,2-13C]acetate, respectively, regardless of citric acid cycle
      intermediate pool sizes or carbon flux through anaplerotic reactions. We also
      show that homonuclear 13C decoupling of the glutamate C2 resonance collapses the
      C3 resonance multiplet into an apparent triplet (actually, a singlet plus a
      doublet); the relative area of the singlet component reflects the amount of
      unlabeled acetyl-CoA entering the cycle. The method has been used to determine
      the contribution of lactate/acetate/glucose to acetyl-CoA in normoxic and
      reperfused rat hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350467
TI  - A soluble factor and GTP gamma S are required for Dictyostelium discoideum
      guanylate cyclase activity.
AB  - Amoeba of Dictyostelium discoideum show a rapid, transient cGMP synthesis in
      response to chemotactic stimulation. Using Mg(2+)-GTP as a substrate, guanylate
      cyclase (E.C. 4.6.1.2.) activity is found exclusively in the particulate fraction
      of Dictyostelium cells. Here we show that the activity is dependent on the
      presence of the non-hydrolysable GTP-analogue GTP gamma S, which itself is only a
      poor substrate for the enzyme under the prevailing conditions. Evidence is
      presented that a transient exposure of the enzyme to GTP gamma S is sufficient to
      constitutively activate the enzyme. GTP gamma S-dependent activity is found to
      require a factor that can be separated from the enzyme by washing the particulate
      fraction with low salt buffer. Addition of the soluble cell fraction to these
      washed membranes restores enzyme activity.

PMID- 1350468
TI  - Growth hormone and renal glutamine and glutamate handling.
AB  - Growth hormone administration effects a positive nitrogen balance in part by
      recycling glutamine nitrogen as glutamate at the expense of ureagenesis. The
      study presented here focuses on the response of the isolated perfused
      hypophysectomized rat kidney to acute growth hormone administration during
      infusions of either glutamine or glutamate. Growth hormone at 50 nM acutely
      decreases the renal utilization of both glutamine and glutamate while enhancing
      reabsorption of the latter. During glutamine infusions of either 1,000 or 500
      nmol/min, growth hormone markedly reduced net glutamine utilization by 55% at the
      high loads and reversed utilization to release at the lower load; associated with
      decreased glutamine utilization was reduced ammonium production and increased
      glutamate release. Although glutamine reabsorption was unchanged, glutamate
      reabsorption increased and NH4+ excretion decreased. During glutamate infusion of
      180 nmol/min, growth hormone reduced glutamate utilization 66%, the residual
      utilization matching increased glutamate reabsorption was associated with
      enhanced bicarbonate reabsorption and a redistribution of NH4+ release into the
      urine; all three responses were eliminated by amiloride. These responses to
      growth hormone are consonant with reduced glutamate oxidation underlying
      decreased glutamine utilization and accelerated luminal Na+-H+ exchange mediating
      luminal transport, events that are conceivably interrelated.

PMID- 1350469
TI  - Helper T cell memory: more questions than answers.
AB  - The critical participation of helper T cells in immunologic memory of animals is
      clear. Features of antigen-specific CD4 memory cells in primed animals that
      distinguish them from naive cells are their increased frequency, their ability to
      secrete lymphokines in addition to IL-2 and their expression of distinct arrays
      of surface molecules. The latter include increased CD44, CD45RO, LFA-3 and VLA-4
      and decreased CD45RA,B and Mel-14. These differences in surface markers may
      contribute to increased interaction potential for APC, and to distinct patterns
      of recirculation, but direct demonstrations of the former have yet to be
      provided. Other possible distinctions that are also largely hypothetical, include
      distinct requirements for activation and the ability to respond more rapidly to
      stimulation. The factors that regulate the development of memory helper T cells
      are also unknown.

PMID- 1350470
TI  - Carrier detection and prenatal diagnosis of hemophilia A: 5-years experience at a
      hemophilia center.
AB  - The identification of carriers and the prenatal diagnosis of hemophilia A have
      greatly improved with knowledge of the structure of the factor VIII gene. This
      has permitted the defect to be traced in families by using restriction fragment
      length polymorphisms. This study summarizes 5 years' experience at A. Bianchi
      Bonomi Hemophilia and Thrombosis Center and the problems encountered. One hundred
      and forty-four women at risk of hemophilia A from 93 families were referred to
      our center for DNA analysis. Carrier detection was performed in 95 women,
      including 11 who were pregnant. Prenatal diagnosis was performed at 7-14 weeks'
      gestation in 56 pregnant women. We employed two intragenic restriction fragment
      length polymorphisms (XbaI and BclI) and the two extragenic restriction fragment
      length polymorphisms (TaqI and BglII). Combining the results of intra and
      extragenic restriction fragment length polymorphisms with pedigree analysis, a
      diagnosis was reached in approximately 90% of cases. Of the 33 male fetuses, 11
      were affected and 19 not affected. Two cases of recombination between extragenic
      restriction fragment length polymorphisms and the factor VIII locus were found.

PMID- 1350472
TI  - Relationship between duration of illness and plasma concentrations of
      antipsychotics in psychotic patients.

PMID- 1350471
TI  - Didanosine.
AB  - OBJECTIVE: To review the chemistry, intracellular metabolism, pharmacokinetics,
      and clinical experience with didanosine (2',3'-dideoxyinosine [ddI]). DATA
      SOURCES: English-language articles and conference proceedings (indexing terms
      were didanosine, 2',3'-dideoxyinosine, and ddI). STUDY SELECTION: Available Phase
      I studies and abstracts determined to have clinical significance were included.
      DATA EXTRACTION: Clinical experience with ddI is limited to uncontrolled Phase I
      studies and a large "expanded-access" program. The primary outcome parameters
      used to evaluate ddI were the HIV surrogate markers: CD4+ lymphocytes and p24
      antigen. Thus, the clinical data reviewed here must be evaluated critically and
      be considered preliminary until the results of studies comparing ddI with
      zidovudine (ZDV) and combination studies are available. DATA SYNTHESIS:
      Didanosine has been approved for the treatment of HIV infection in patients who
      are unable to tolerate ZDV because of adverse effects (e.g., anemia and
      neutropenia) or who experience clinical or immunologic deterioration while
      receiving ZDV. Compared with ZDV, ddI has a long intracellular half-life and
      negligible bone-marrow toxicity. It also has in vitro activity against ZDV
      resistant strains of HIV. Phase I studies indicate that ddI has a beneficial
      effect on the CD4+ cell counts and HIV p24 antigen concentrations. As a result of
      the acid-labile nature of ddI, oral formulations are buffered or must be mixed
      with antacid to neutralize gastric pH. Bioavailability then averages 20-40
      percent, depending on the dose and formulation given. The plasma half-life, total
      body clearance, and volume of distribution of ddI are one to two hours, 0.7-1
      L/kg/h, and 0.8-1 L/kg, respectively. Painful peripheral neuropathy and
      pancreatitis (dose-limiting toxicities of ddI) occurred in 34 and 9 percent of
      patients in Phase I studies, respectively. CONCLUSIONS: Didanosine has
      demonstrated preliminary efficacy in the treatment of late-stage HIV infection;
      however, its effect on patient survival, its efficacy relative to ZDV, and its
      utility in combination with other agents are still under evaluation.

PMID- 1350474
TI  - Alpha-linolenic acid vs. long-chain n-3 fatty acids in hypertension and
      hyperlipidemia.

PMID- 1350473
TI  - Clinical studies with alpha-linolenic acid and long-chain n-3 fatty acids.

PMID- 1350475
TI  - Relationships of alpha-linolenic acid to platelet fatty acid composition and
      trans content of cholesterol-free foods.

PMID- 1350476
TI  - Regulation of total ovarian glutathione content in the rat.
AB  - Glutathione (GSH) is an important intracellular thiol capable of altering
      metabolism following exposure to certain important biologic toxicants including
      radiation and cyclophosphamide. In order to evaluate the inhibition of
      glutathione synthesis in the ovary, 30-day-old Sprague Dawley rats were treated
      with either saline or 0.6 mumol/kg (0.133 mg/kg), 6.0 mumol/kg (1.33 mg/kg), or
      4.5 mmol/kg (1000 mg/kg) buthionine sulphoximine (BSO) IP and sacrificed at 0, 1,
      2, 4, 6, 8, and 24 h. There was an inhibition of glutathione synthesis with 4.5
      mmol/kg (1000 mg/kg) BSO with a nadir at 8 h (P less than 0.001) and complete
      recovery at 24 h. In the subsequent experiments rats were divided into four
      groups. All animals received either saline or BSO 4.5 mmol/kg/day (1000
      mg/kg/day) from day 27 to 30 of life and either saline or PMSG 5 IU IP on day 29
      of life. BSO reduced ovarian content of GSH (saline-saline compared with BSO
      saline, P less than 0.0001), which was countered by the prior administration of
      PMSG (BSO-saline compared with BSO-PMSG, P less than 0.005). Glutathione levels
      were as follows: saline-saline 4.3 +/- 0.04; saline-PMSG 5.0 +/- 0.4; BSO-saline
      2.13 +/- 0.2; BSO-PMSG 3.24 +/- 0.2 nmol/mg ovary. These findings suggest the
      ovary is susceptible to GSH depletion by in vivo administration of BSO.
      Gonadotropin (PMSG) is capable of effecting a partial return of total ovarian GSH
      content.

PMID- 1350477
TI  - Carvedilol: a new approach to antihypertensive therapy. Proceedings from
      International Symposium on Carvedilol. Berlin, March 14-17, 1991.

PMID- 1350478
TI  - Effects of carvedilol on adrenergic receptor pharmacology in human ventricular
      myocardium and lymphocytes.
AB  - Carvedilol, a new beta-blocker with vasodilating properties due to alpha 1
      blockade, was investigated in preparations of human ventricular myocardium.
      Carvedilol demonstrated a high affinity and is a slightly beta 1-selective
      competitive beta-blocking agent, with a KD for beta 1-receptors of approximately
      4-5 nM and a mild selectivity for beta 1 vs. beta 2 receptors of 6- to 39-fold,
      depending on the method employed to assess subtype potency. In addition,
      carvedilol was also a potent alpha 1-blocking agent, with a beta 1:alpha 1
      blocking relative potency of 1.7-fold. In human lymphocytes containing beta 2
      receptors and in human myocardial membranes containing both beta 1- and beta 2
      receptors carvedilol exhibited the unique property of guanine nucleotide
      modulatable binding. Despite this, no intrinsic sympathomimetic activity of
      carvedilol was detected in preparations of isolated human heart or in myocardial
      membranes. Vasodilation related to alpha 1-blockade and the lack of intrinsic
      activity should translate into improved tolerability and good efficacy in the
      treatment of heart failure.

PMID- 1350479
TI  - Carvedilol and the kidney.
AB  - Antihypertensive drugs have differing effects on renal hemodynamics, tubular
      function, plasma electrolytes, and hormonal responses. Nonselective beta-blockers
      without intrinsic sympathomimetic activities, such as propranolol, have been
      reported to reduce renal blood flow and to cause a modest decrease in glomerular
      filtration rate. Carvedilol is a new multiple action agent displaying
      nonselective beta-blockade without intrinsic sympathicomimetic activity, alpha 1
      adrenoceptor blockade (probably responsible for its vasodilator activity), and
      possibly also calcium antagonist properties. The presence of these different
      pharmacodynamic properties results in a different effect on the kidney as
      compared with, e.g., propranolol. In the dog, intrarenal infusion of carvedilol
      resulted in a renal vasodilator response with preservation of renal blood flow
      and without inducing sodium retention; in contrast, propranolol induced a renal
      vasoconstrictor response and sodium retention in this model. A renal vasodilator
      response to carvedilol was also reported in spontaneously hypertensive rats (SHR)
      and in DOCA-salt SHR. In contrast to labetalol, i.v. infusion of hypotensive
      doses of carvedilol in conscious SHR did not cause sodium retention. Carvedilol
      was effective in controlling hypertension and preserving renal function in a rat
      model of progressive hypertensive renal disease. In patients with essential
      hypertension, carvedilol was reported to reduce renal vascular resistance in the
      presence of reduced perfusion pressure, allowing for normal renal autoregulation
      of renal blood flow. Although a small reduction in glomerular filtration rate was
      seen after acute administration, renal function was preserved during chronic
      treatment. It is concluded from these studies that renal perfusion and renal
      function are well maintained during acute and chronic treatment with
      carvedilol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350480
TI  - Pharmacological profile of beta-adrenoceptor blockers with vasodilating
      properties, especially carvedilol--rationale for clinical use.
AB  - The rationale for the combined use of beta-adrenoceptor antagonists and
      vasodilators is to improve the efficacy of the antihypertensive therapy and to
      reduce the incidence of side effects. If suitable coagents are selected and used
      at appropriate doses, the disadvantages of each separate component (compromised
      blood flow to individual organs, increase in total peripheral resistance,
      unfavorable lipid profile for beta-blockers; stimulation of counter-regulatory
      mechanisms, retention of water and electrolytes for vasodilators) can be
      balanced. In addition, the favorable effects of each (reduction in cardiovascular
      morbidity and mortality for beta-blockers, and favorable hemodynamic profile for
      vasodilators) may be used to advantage. Such a treatment rationale can be
      accomplished by a free combination or by using a dual-acting drug. From the
      practical point of view, the latter may be preferable. The basic requirement for
      such a drug is that the two effects are evoked in the same dose range. Carvedilol
      is a dual-acting drug designed to produce beta-blockade and vasodilation in the
      same dose range. The vasodilation is mediated predominantly by specific alpha 1
      adrenoceptor blockade; at markedly higher concentrations additional vasodilating
      actions can be observed. These effects resemble those of Ca(2+)-antagonistic
      properties. However, they do not contribute to the acute blood-pressure-lowering
      activity, but may be responsible for the increased blood flow to some organs. At
      beta-blocking doses, carvedilol reduces the total peripheral resistance, and
      blood flow to the kidneys is preserved. Cardioprotection has been demonstrated in
      a variety of experimental investigations.

PMID- 1350481
TI  - Clinical pharmacology of carvedilol.
AB  - Animal work has shown that carvedilol is a nonselective beta-blocking drug. It
      has a vasodilator action from alpha-receptor blockade, but there is evidence that
      it has further action to relax smooth muscle, possibly from calcium channel
      antagonism. Carvedilol is lipid soluble and 25% bioavailable, and it has a half
      life of about 7 h. It lowers blood pressure at rest and reduces the tachycardia
      and the rise of blood pressure on exercise. It reduces the level of blood
      pressure reached during isometric exercise or the cold pressor test. Cardiac
      output at rest is maintained, and the haemodynamics in the compromised heart is
      improved. It has an important peripheral vasodilator action, peripheral flow
      being maintained to important organs, e.g. kidneys, despite the fall in blood
      pressure. Exercising renin and noradrenaline levels are increased, as are the
      latter at rest. Carvedilol is lipid neutral. Carvedilol shifts the dose-response
      curve to isoprenaline to the right, as well as to alpha-stimulants such as
      phenylephrine. Responses to angiotensin are little affected. The ratio of beta-
      to alpha-blockade has been found to be 7.6 for 50 mg and 12.5 for 100 mg of
      carvedilol. There is no evidence of a decline in alpha-blockade after 1 week of
      continuous administration.

PMID- 1350483
TI  - Clinical experience with dual-acting drugs in hypertension.
AB  - There are now several antihypertensive agents with dual actions. Among these,
      labetalol has been studied most extensively. The drug has a place in the chronic
      treatment of hypertension and in the therapy of hypertensive emergencies.
      Carvedilol, now available in Germany, has been shown to be effective in different
      forms of hypertension. Celiprolol binds to beta 1- and beta 2-receptors. This
      drug also binds to alpha 2-receptors. It is not clear, at present, whether or not
      this binding property contributes to its antihypertensive effect.

PMID- 1350482
TI  - Antihypertensive effect of carvedilol: a preliminary dose-response study.
AB  - The blood pressure (BP) lowering effect of low doses of antihypertensive agents
      is not usually explored because of the difficulty in detecting small changes in
      BP. Since ambulatory blood pressure monitoring in a cross-over trial design can
      reliably detect differences of 5 mmHg with less than 20 subjects, we have used
      this technique to assess the dose-response curve of a new beta-blocker,
      carvedilol. Twenty subjects were enrolled after diagnostic ambulatory BP
      monitoring had shown a day-time average diastolic BP of over 90 mmHg. Three doses
      of carvedilol (6.25, 12.5 and 25 mg daily) and placebo were then given double
      blind in random order for periods of 4 weeks each. No period effects were
      detected. The antihypertensive effect was statistically significant at doses of
      12.5 mg and 25 mg daily. There was, however, no evidence that 25 mg/day produced
      the peak effect. The lowest dose (6.25 mg/day) produced a small fall in both
      systolic and diastolic BP but neither of these were significant. We conclude that
      doses of 12.5 and 25 mg carvedilol once a day are adequate for the treatment of
      hypertension.

PMID- 1350484
TI  - Antihypertensive profile of carvedilol.
AB  - The spectrum of demands on an antihypertensive agent is constantly increasing. It
      is not only supposed to reduce blood pressure, but also to have a certain profile
      with regard to pathophysiology, hemodynamics, pharmacokinetics, safety, and
      clinical applicability. Carvedilol is a new beta-blocking agent without ISA,
      which causes vasodilation primarily through an alpha 1-blockade. It combines the
      positive effects of alpha 1- and beta-blockade; the negative properties are
      offset by each other. It not only provides theoretical advantages, but also shows
      a favourable hemodynamic profile and is effective and safe. Advantages in both
      primary and secondary prevention can be expected. It can be administered once
      daily, is well suited to patient needs, and can be combined with other
      hypertensive drugs. It also exerts a favorable influence on many secondary
      diseases. The compelling advantages of the drug make it an important addition to
      our armamentarium for the treatment of arterial hypertension as a first-line
      drug.

PMID- 1350486
TI  - Long-term hemodynamic effects of antihypertensive treatment.
AB  - The cardinal hemodynamic disorder in established essential hypertension is
      increased total peripheral resistance. During exercise, the increase in stroke
      volume of the heart is abnormal. A 20-year follow-up study of the hemodynamics in
      essential hypertension demonstrated a progressive increase in total peripheral
      resistance and deterioration of the heart pump function. Long-term treatment with
      antihypertensive agents modifies the circulatory system in different ways.
      Vasodilators (angiotensin converting enzyme inhibitors, alpha 1-blockers, and
      calcium antagonists) all reduce total peripheral resistance, and in general,
      cardiac output, heart rate, and stroke volume remain unchanged. Calcium
      antagonists like verapamil and diltiazem reduce the heart rate approximately 10%
      during exercise, but since stroke volume increases, cardiac output is unchanged.
      Chronic treatment with conventional beta-blockers induces a permanent reduction
      in cardiac output and heart rate during exercise. In contrast, carvedilol--a beta
      1,beta 2-blocker with alpha 1-blocking activity--prevents the immediate increase
      in total peripheral resistance during acute beta-blockade. In 19 patients
      followed by hemodynamic measurements over 6-9 months, blood pressure was well
      controlled by carvedilol. During exercise, total peripheral resistance decreased
      6% (P less than 0.05), and the reductions in heart rate and cardiac index were
      less than on conventional beta-blockade. Echo-Doppler studies showed a
      significant reduction in the intraventricular septum of 13%.

PMID- 1350485
TI  - Comparison of the antihypertensive effects of carvedilol and metoprolol on
      resting and exercise blood pressure.
AB  - The present study was conducted to assess the efficacy and safety of carvedilol
      50 mg as compared to metoprolol 200 mg at rest and during and after a
      standardized bicycle ergometric exercise test. Carvedilol is a novel non
      selective beta-blocker without intrinsic sympathomimetic activity possessing
      vasodilatory properties primarily due to an alpha 1-antagonism in the same dose
      range. Both drugs were effective in reducing systolic and diastolic blood
      pressure at rest and during and after exercise. The reduction of diastolic blood
      pressure was much stronger under carvedilol treatment than under metoprolol
      treatment at all measurement points. Carvedilol was even effective in the
      treatment of patients whose blood pressure was unsatisfactorily controlled by
      metoprolol. This shows the importance of the vasodilation component of
      carvedilol. No serious adverse events were observed. Carvedilol therefore
      promises very well as a powerful and safe drug for the treatment of essential
      arterial hypertension.

PMID- 1350487
TI  - Hemodynamic and metabolic effects of carvedilol: a meta-analysis approach.
AB  - Establishing the overall efficacy or safety of a drug requires a unified
      methodological approach and analysis of all clinical trials to be included. As an
      example, this paper presents the aggregated dose-response relationship of
      efficacy data and a last-value analysis of laboratory data across all studies of
      the antihypertensive drug project carvedilol. Hemodynamic endpoints were
      calculated as change from the baseline blood pressure and pulse after an average
      treatment of 2-4 weeks whereas metabolic endpoints were calculated as changes
      from the baseline until the last day with respect to glucose, potassium,
      creatinine, lipids and liver function (median duration of treatment was 8-12
      weeks). All antihypertensive trials were reanalyzed using an intent-to-treat
      principle. Aggregated efficacy data (mean, standard deviation, sample size) for
      each allocated group within each study were combined by means of meta-analysis
      separately for o.d. or b.i.d. dose regimens. Laboratory data were aggregated
      similarly within each study, using the last active drug as a grouping factor. The
      results showed that the patient population was treated adequately with 25 mg
      carvedilol o.d. The dose response curve for o.d. regimens shows a typical sigmoid
      shape: a steeper increase from 12.5 mg to 25 mg carvedilol, which then flattens
      (25 mg, 50 mg, 100 mg carvedilol o.d.). No superiority of a b.i.d. dose regimen
      over a o.d. dose regimen by means of BP lowering could be detected. There was a
      considerable variation in the results between studies, much bigger than the dose
      response effect, most due to monocentric trials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350488
TI  - The role of alpha- and beta-adrenoceptor blockade in antihypertensive treatment.
AB  - The alpha and beta-adrenoceptors are at present subdivided into alpha 1/alpha 2
      and beta 1/beta 2 (probably also beta 3) subtypes. This subdivision, based on
      functional pharmacological studies, has been largely confirmed by molecular
      biological techniques. At presynaptic sites alpha 2- and beta 2-adrenoceptors are
      known to predominate, whereas both alpha 1/alpha 2- and beta 1/beta 2-receptors
      may be found at postsynaptic sites. This subdivision and classification of
      adrenoceptors, receptor changes in disease, and the availability of agonists and
      antagonists for the various receptor subtypes are discussed as the basis for
      antihypertensive drug therapy. alpha-Adrenoceptor antagonists are vasodilators,
      which owe their antihypertensive activity to arterial vasodilatation, while
      venous dilatation occurs simultaneously. Selective alpha 1-antagonists (prazosin,
      doxazosin) are preferable to the older nonselective compounds like phentolamine.
      beta-Blockers are useful antihypertensive agents used on a very large scale, but
      their mode of action remains unknown in detail. The combination of alpha- and
      beta-adrenoceptor blockade would be attractive, particularly for hemodynamic
      reasons. alpha-Adrenoceptor blockade reduces peripheral vascular resistance but
      also counteracts the vasoconstrictor effect of beta-blockers in the extremities,
      underlying the well-known side-effect of cold hands and feet. beta-Adrenoceptor
      blockade will not only contribute to the hypotensive effect but also suppress
      reflex tachycardia induced by alpha-adrenoceptor blockade.

PMID- 1350489
TI  - Pathophysiology and triggers of acute myocardial infarction: clinical
      implications.
AB  - A new approach to identification of the triggering mechanisms of acute myocardial
      infarction has been provided by the observation that the disease occurs more
      frequently during the morning hours compared to other times of day. This
      circadian variation results primarily from an increased relative risk during the
      initial 2-3 h after awakening and arising. The precise relationship between the
      onset of myocardial infarction and external factors such as activity and meal
      patterns needs to be determined in controlled epidemiologic studies. The possible
      underlying pathophysiologic mechanisms responsible for the circadian pattern of
      myocardial infarction include acute variations of blood pressure, heart rate,
      platelet aggregability and fibrinolytic activity, leading to an increased risk of
      plaque rupture and intracoronary thrombosis. Clinical implications of these
      findings include the need to design preventive regimens to provide maximum
      protection at the time of peak risk of myocardial infarction.

PMID- 1350490
TI  - Left ventricular hypertrophy regression during antihypertensive treatment.
AB  - For more than 20 years hypertrophy regression has been in the focus of
      hypertension research. Many studies in animals have shown impressive reduction of
      left ventricular hypertrophy after medical treatment of hypertension. The most
      important result seems to be that hypertrophy can be almost completely reversed
      in young animals, whereas in older animals regression of left ventricular
      hypertrophy appears to be less complete. Hypertrophy regression in man seems much
      more difficult to prove. The direct correlation between left ventricular muscle
      mass and ECG changes has been disappointing in many studies. Echocardiography is
      able to show a comparatively good impression of left ventricular muscle mass and
      therefore can also demonstrate regression of left ventricular hypertrophy within
      its methodological limits. There is no doubt that today magnetic resonance
      imaging has by far the best imaging quality of all the clinical methods and is
      able to demonstrate both hypertrophy and its regression with incomparable
      accuracy. In the present clinical study hypertrophy regression has been
      demonstrated after 6 months of treatment with Carvedilol.

PMID- 1350491
TI  - Acute hemodynamic effects of carvedilol in comparison with propranolol in
      patients with coronary heart disease.
AB  - In a randomized, double-blind study oral doses of 50 mg carvedilol (Dilatrend)
      were compared with 40 mg propranolol in 16 male patients with coronary heart
      disease, CHD [12 without significant stenoses following percutaneous transluminal
      coronary angioplasty (PTCA), 4 with multivessel disease]. Bicycle ergometry in
      the supine position was performed before and 80 min after drug application;
      measurements were done at rest, during and after exercise. Clinically, the total
      exercise time and the onset of angina and exhaustion were noted, while the
      investigated hemodynamic parameters were heart rate, systemic and pulmonary
      pressures and resistances, cardiac index, and lower limb blood flow. Clinically,
      carvedilol improved the exercise tolerance more than propranolol as regards
      angina and exhaustion. Hemodynamically, carvedilol did not lead, as the classic
      betablocker propranolol does, to an increase in systemic or pulmonary resistance,
      to a decrease in cardiac output, or to an increase of the pulmonary capillary
      wedge pressure during exercise, but instead caused opposite changes. In contrast
      to propranolol, the post exercise lower limb blood flow had increased
      significantly. The differences in action between the two betablockers can be
      explained by the vasodilating properties of carvedilol. Due to these acute
      effects, carvedilol may be preferred to propranolol in the treatment of CHD
      patients with hypertension, peripheral occlusive artery disease, and/or coronary
      vasospasm.

PMID- 1350492
TI  - Can intravenous beta blockade predict long-term haemodynamic benefit in chronic
      congestive heart failure secondary to ischaemic heart disease? A comparison
      between intravenous and oral carvedilol.
AB  - Several studies in the past have shown the long-term beneficial effects of beta
      blockers in congestive heart failure. Despite the interest in this mode of
      therapy, their clinical application has been limited due to their negative
      inotropic effect. A subset of the heart failure patients do not show any
      improvements with standard beta-blocker therapy. Carvedilol, a new, non-selective
      beta-blocking agent with concurrent alpha-blocking properties, was evaluated in
      17 patients with chronic heart failure secondary to ischaemic heart disease. All
      had resting left ventricular ejection fraction less than or equal to 45% and were
      maintained on diuretic therapy. Acute haemodynamic measurements were made after
      intravenous carvedilol (2.5-7.5 mg) and also after chronic therapy for 8 weeks
      (carvedilol 12.5-50 mg b.d.). Radionuclide ventriculography, ambulatory intra
      arterial blood pressure monitoring and right heart catheterization were performed
      before and after 8 weeks of chronic therapy. Twelve patients completed the study
      and 5 were withdrawn. Symptomatic and haemodynamic improvement was demonstrated
      in 11 of the 12 patients after 8 weeks of therapy.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1350493
TI  - Co-prescription of anticholinergic drugs with neuroleptics.

PMID- 1350494
TI  - Effect of psychotropic drugs on excitatory amino acids in patients undergoing
      psychosurgery for depression.
AB  - Samples of ventricular CSF were taken from 52 consecutive patients admitted for
      psychosurgery for intractable depression. Concentrations of asparagine,
      aspartate, glutamine, glutamic acid, and serine were determined. Glutamate and
      aspartate concentrations, implicated in excitotoxic brain damage, were not
      affected by various types of psychotropic drug treatment. Serine, a modulator of
      glutamate responses, was significantly elevated in samples from subjects
      receiving antidepressants. These subjects responded poorly to the operation.
      Psychotropic drugs are unlikely to be neurotoxic. Nevertheless, antidepressants
      may influence excitatory neurotransmission.

PMID- 1350495
TI  - The effect of neuroleptics on cognitive and psychomotor function. A preliminary
      study in healthy volunteers.
AB  - The effects of haloperidol (1 mg), benzhexol (5 mg), diazepam (10 mg) and
      caffeine (400 mg) on subjective and objective measures of cognitive and
      psychomotor function were compared with placebo in 20 healthy volunteers. While
      both diazepam and benzhexol were associated with highly significant impairments
      in subjective altertness, critical flicker fusion threshold and choice reaction
      time (CRT), haloperidol could not be distinguished from placebo in most tests but
      was actually associated with an apparent improvement in CRT (in males) and simple
      visual reaction time. The perceptual maze test detected impairment by benzhexol
      on processing speed but was not sensitive to any other drug effects. Multiple
      dose studies are required to establish if there is a true activating effect of
      haloperidol using a test of sustained attention. No effect of Eysenck personality
      subtype or life events on baseline or drug response data was detected.

PMID- 1350496
TI  - Dissociation of serotoninergic and dopaminergic components in acute effects of 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice.
AB  - Behavioural and neurochemical effects of acute 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) treatment in mice have been studied in order to
      determine the change in the neurotransmitter profile of the following areas of
      the brain: substantia nigra (SN), nucleus caudatus putamen (NCP), limbic system
      (LS; tuberculum olfactorium and nucleus accumbens), medulla oblongata (MO) and
      cerebellum (CER). Subcutaneous administration of MPTP (40 mg/kg) caused
      behavioural syndromes including restlessness, straub tail, hindlimb abduction,
      tremor, jumping, bradykinesia and akinesia in Balb/c mice. There existed a well
      defined biphasic profile of motor activity comprising of an initial excitatory
      phase followed by an inhibitory phase lasting about two and a half and five
      hours, respectively. A significant rise in 5-hydroxytryptamine (5-HT) content
      together with a decreased 5-HT utilization as evidenced by lower 5-hydroxyindole
      acetic acid (5-HIAA) to 5-HT ratio in the above brain areas demarcated the
      excitatory phase, whereas the inhibitory phase was distinguished by a significant
      decrease in dopamine (DA) content along with an increased turnover of the amine
      as shown by a higher homovanillic acid (HVA) to DA ratio in the functionally
      important nuclei of the extrapyramidal system like SN, NCP and LS. Methysergide,
      a nonspecific 5-HT receptor blocker, but not ketanserin, a specific 5-HT2
      antagonist, prevented the occurrence of the initial excitatory phase without
      affecting the depressive phase. Administration of apomorphine, a dopamine
      agonist, 30 minutes prior to MPTP was ineffective, whereas its application 90
      minutes after MPTP prevented the occurrence of bradykinesia and akinesia.
      Interestingly, treatment with haloperidol, the dopamine (D1/D2) antagonist,
      before and after MPTP administration caused an early onset and prolongation of
      the inhibitory phase without affecting the initial hyperexcitement. The results
      provide direct evidence for the involvement of serotoninergic and dopaminergic
      mechanisms in the genesis of the early and late syndromes of acute MPTP poisoning
      respectively.

PMID- 1350498
TI  - Norepinephrine increases angiotensin II binding in rat brain synaptosomes.
AB  - Synaptosomes prepared from rat hypothalamus or brainstem contain specific binding
      sites for [125I]-angiotensin II (AII). Treatment of these synaptosomes with
      norepinephrine (NE) (10-500 microM) for 60 min results in a concentration
      dependent increase in [125I]-AII specific binding which appears to be an increase
      in the number rather than the affinity of these binding sites. This effect of NE
      is qualitatively similar in synaptosomes prepared from neonate (one-day-old) or
      adult (140-day-old) rats. Furthermore, it is antagonized by prazosin (10 microM)
      but not by yohimbine (10 microM), indicating the involvement of alpha 1
      adrenergic receptors. Finally, this effect of NE may involve activation of
      protein kinase C (PKC) because it is mimicked by a PKC agonist (TPA, 0.8 microM;
      60 min) and is blocked by a PKC antagonist (H-7, 100 microM). These results match
      our previous findings on the regulation of AII receptors in neurons cultured from
      the hypothalamus and brainstem of neonate rats and provide strong evidence for a
      role of this catecholamine in the modulation of brain AII receptors.

PMID- 1350497
TI  - Synaptic potentials and effects of amino acid antagonists in the auditory cortex.
AB  - Neurons of in vitro guinea pig and rat auditory cortex receive a complex synaptic
      pattern of afferent information. As many as four synaptic responses to a single
      stimulus pulse to the gray or white matter can occur; an early-EPSP followed,
      sequentially, by an early-IPSP, late-EPSP, and late-IPSP. Paired pulse
      stimulation and pharmacological studies show that the early-IPSP can modify
      information transmission that occurs by way of the early-EPSP. Each of these four
      synaptic responses differed in estimated reversal potential, and each was
      differentially sensitive to antagonism by pharmacological agents. DNQX (6,7
      dinitroquinoxaline-2,3-dione), a quisqualate/kainate receptor antagonist, blocked
      the early-EPSP, and the late-EPSP was blocked by the NMDA receptor antagonist APV
      (D-2-amino-5-phosphonovalerate). The early-IPSP was blocked by the GABA-a
      receptor antagonist bicuculline, and the late-IPSP by the GABA-b receptor
      antagonists 2-OH saclofen or phaclofen. Presentation of stimulus trains, even at
      relatively low intensities, could produce a long-lasting APV-sensitive membrane
      depolarization. Also discussed is the possible role of these synaptic potentials
      in auditory cortical function and plasticity.

PMID- 1350499
TI  - Ethanol inhibits epileptiform activity and NMDA receptor-mediated synaptic
      transmission in rat amygdaloid slices.
AB  - The effect of ethanol on the epileptiform activity induced by Mg(++)-free
      solution was studied in rat amygdalar slices using intracellular recording
      techniques. The spontaneous and evoked epileptiform discharges consisting of an
      initial burst followed by afterdischarges were observed 20-30 min after switching
      to Mg(++)-free medium. Superfusion with ethanol (20-100 mM) reversibly reduced
      the duration of spontaneous and evoked bursting discharges in a concentration
      dependent manner. Synaptic response mediated by N-methyl-D-aspartate (NMDA)
      receptor activation was isolated by application of a solution containing the non
      NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and either
      in Mg(++)-free solution or in the presence of 50 microM bicuculline. Application
      of ethanol reversibly suppressed the duration of NMDA receptor-mediated synaptic
      response. These results suggest that intoxicating concentrations of ethanol
      possess anticonvulsant activity through blocking the NMDA receptor-mediated
      synaptic excitation. In addition, the observed effect of ethanol on NMDA receptor
      mediated synaptic response could be relevant to the cognitive and behavioral
      manifestations seen in some alcoholics.

PMID- 1350501
TI  - Benzodiazepine reversal with flumazenil--a review of the literature.
AB  - Benzodiazepines such as Valium (diazepam) or Versed (midazolam), as used in
      dental procedures for intravenous sedation, have been a boon to the profession.
      Yet in the event of sedation problems, no agent exists that consistently reverses
      all clinical effects of these drugs. This problem does not exist with narcotics,
      frequently employed in tandem with benzodiazepines, since an effective reversal
      agent, Narcan (naloxone hydrochloride), exists. It would be advantageous to
      effectively reverse benzodiazepines in cases of acute emergency with respiratory
      depression or paradoxical reactions, and to allow quick, full recovery after
      short dental procedures. None of the drugs currently available for benzodiazepine
      reversal, such as physostigmine, give consistent clinical results. The purpose of
      this paper is to discuss Flumazenil, a new specific benzodiazepine receptor
      antagonist, and its possible use for dental sedation procedures.

PMID- 1350500
TI  - Subtypes of substantia nigra dopaminergic neurons revealed by apamin:
      autoradiographic and electrophysiological studies.
AB  - In the intact animal, some substantia nigra dopaminergic neurons exhibit regular,
      and some exhibit burst firing patterns. In the in vitro slice preparation,
      however, all dopaminergic neurons exhibit a nonburst firing pattern. Burst firing
      patterns are thought to be regulated, in part, by a small conductance calcium
      activated potassium channel (SK channels). To test whether SK channels reside
      within the midbrain dopaminergic cell regions of the mouse, receptor
      autoradiographic experiments were conducted with the SK channel antagonist, 125I
      apamin. To determine whether SK channels play a role in burst firing pattern
      generation in substantia nigra dopaminergic neurons, changes in firing patterns
      of these cells were examined in the in vitro slice preparation following apamin
      superfusion (1-1000 nM). It was demonstrated that a) specific binding of
      radiolabeled apamin was found within the dopaminergic cell regions of the
      substantia nigra pars compacta, and ventral tegmental area (2.7-4.7 fmol/mg
      tissue); b) the firing patterns of less than half of the dopaminergic neurons
      were changed from a regular pattern to that of a burster with concentrations as
      low as 1 nM, but the firing patterns of many neurons were not changed by the
      drug; and c) blockade of the SK channel did not interfere with the inhibitory
      effects of dopamine on dopaminergic neuronal impulse flow, indicating that the
      known hyperpolarizing effects mediated by this dopamine receptor are not
      importantly mediated via the SK channel.

PMID- 1350502
TI  - The pharmacoepidemiology of treatment-refractory schizophrenia.
AB  - Treatment-refractory schizophrenia is a major clinical problem for which there is
      relatively little scientific information, and no consensus has been reached on
      approaches to treatment. The pharmacotherapy used for 103 patients with a
      diagnosis of schizophrenia or schizoaffective disorder at one psychiatric
      hospital was examined. Data were gathered on neuroleptic choice and dose, the use
      of adjunctive treatments and serum neuroleptic levels. The daily neuroleptic dose
      was compared with that of random samples of patients receiving outpatient
      maintenance treatment, and short-stay patients receiving acute treatment. The
      patients in our sample received high doses of neuroleptics despite a persistent
      lack of response to treatment, and despite the fact that these were in excess of
      the recommended maximum beneficial dose. The appropriateness of this therapy is
      discussed.

PMID- 1350503
TI  - Can drug-induced depressions be identified by their clinical features?
AB  - Drug-induced depression is classified by the DSM-III-R as an organic mood
      syndrome of the depressed type. Because drugs have specific pharmacological
      effects and mechanisms of action, depressive syndromes induced by specific drugs
      may have characteristic clinical features. An awareness of such features would be
      valuable for clinical purposes. This review is an attempt to summarize the
      information on clinical features of drug-induced depressions. The review
      determined that no unique clinical features have been identified for depressive
      syndromes associated with most drugs. However, the literature did suggest that
      depressions associated with oral contraceptive agents may differ significantly
      from non organic major depressive episodes.

PMID- 1350504
TI  - C-erbB-2 oncoprotein expression versus internal mammary lymph node metastases as
      additional prognostic factors in patients with axillary lymph node-positive
      breast cancer.
AB  - The relationship was assessed between c-erbB-2 oncoprotein expression and other
      prognostic factors in breast cancer, such as axillary and internal mammary node
      metastases. The value of these indicators was analyzed in estimating prognosis,
      especially in patients with axillary node-positive breast cancer. These results
      showed that c-erbB-2 is significantly related to clinical stage and axillary node
      metastases. A univariate study revealed that disease-free and overall survival
      were correlated significantly with clinical stage, tumor size, axillary and
      internal mammary node metastases, and 21N status. Among the patients with
      axillary node involvement, however, 21N status did not appear to be a significant
      additional prognostic factor. Internal mammary node metastases were significant.
      In a multivariate study, only axillary and internal mammary node metastases were
      significant prognostic factors for either the entire group of patients or those
      with positive axillary nodes. Therefore, axillary node dissection and biopsy of
      the internal mammary nodes may provide important prognostic information for
      patients with breast cancer.

PMID- 1350505
TI  - Cowden's disease. A case report with analyses at the molecular level.
AB  - Cowden's disease (multiple hamartoma syndrome) is characterized by multiple
      hamartomas of ectodermal, endodermal, and mesodermal origin, a high incidence of
      malignant tumors of the breast and/or thyroid gland, and an autosomal dominant
      pattern of inheritance. Similar to sporadic breast cancer, chromosomal studies
      have not elucidated the cause of this syndrome. The authors report the case of a
      patient with this syndrome and analyze the pattern of amplification or
      rearrangement of three genes: the HER-2/neu oncogene, the ras oncogene, and the
      estrogen-inducible gene, pS-2. All three of these genes were present in single
      copies without translocations. It was noteworthy that three of the most important
      genes currently studied in relation to breast cancer existed in a unamplified
      unrearranged state in this patient. Those with clinical manifestations of
      Cowden's disease may be candidates for prophylactic bilateral total mastectomy,
      and the authors recommend that these patients undergo this procedure by their
      third decade of life. An alternative to this approach would entail monthly self
      examinations, breast examinations by the patient's physician every 3 months,
      bilateral mammograms every 6 to 12 months, and biopsy of any suspicious lesions.
      It is crucial, however, that these patients be identified by their mucocutaneous
      lesions and family history before an underlying malignant lesion develops.

PMID- 1350506
TI  - Multiple drug resistance gene expression in human renal cell cancer is associated
      with the histologic subtype.
AB  - Overexpression of p170 glycoprotein, the product of the multiple drug resistance
      (mdr) gene, has been associated with resistance to various cytotoxic drugs used
      in the treatment of human neoplasms. Normal renal epithelial cells express p170
      as a function of their secretory capacity. Because renal cell carcinomas (RCC)
      respond poorly to chemotherapeutic regimens, p170 expression was studied in
      primary RCC. Such expression was measured in 40 human RCC and normal kidney
      tissues using immunohistochemical staining with the monoclonal antibody C-219.
      Staining intensities of the whole tumor and of different areas of the cryostat
      sections were transformed into digital numbers using an algorithm designed for
      this purpose. In most tumors, an inhomogeneous staining pattern and a correlation
      between grade of differentiation and C-219 immunoreactivity was observed. A
      comparison of the tumors according to their histopathologic subtypes showed clear
      differences. The means (range) of the staining intensities of the different types
      of RCC: clear cell carcinoma Grade 1 (n = 3), 2.0 (2.0 to 2.0); clear cell
      carcinoma Grade 2 (n = 19), 0.8 (0.0 to 2.9); clear cell carcinoma Grade 3 (n =
      5), 0.1 (0.0 to 0.2); tubular carcinoma (n = 4), 2.0 (2.0 to 3.0); anaplastic
      carcinoma (n = 8), 0.05 (0.0 to 0.2); oncocytoma (n = 1), 0.0 (0.0 to 0.0); and
      normal kidney (n = 40), 0.5 (0.0 to 2.0). The differences between anaplastic,
      clear cell, and tubular carcinoma were significant (P less than 0.001 by Kruskal
      Wallis test). In addition, the difference between the three subgroups of clear
      cell carcinoma was significant (P less than 0.01). It was concluded that the
      histopathologic subtypes of RCC correlate with the degree of mdr gene expression,
      as determined by staining with the C-219 monoclonal antibody.

PMID- 1350507
TI  - Multidrug-resistant phenotype of disease-oriented panels of human tumor cell
      lines used for anticancer drug screening.
AB  - Disease-oriented panels of human tumor cell lines used by the National Cancer
      Institute for large-scale in vitro anticancer drug screening were evaluated for
      multidrug-resistant phenotype at the functional (in vitro drug sensitivity) and
      molecular levels. The cell line panels manifested a broad range of sensitivities
      to drugs typically associated with multidrug resistance (MDR) as well as to drugs
      not associated with MDR. Individual cell lines displayed unique and
      characteristic profiles of response. Patterns of correlated response were
      observed among, but not between, MDR and non-MDR drugs. Strong evidence of
      correlated response was limited to drugs sharing an intracellular mechanism of
      action. Several tumor cell lines exhibited a high degree of resistance to MDR
      drugs and relative sensitivity to non-MDR drugs, contained high levels of MDR-1
      mRNA, and expressed cell surface P-glycoprotein detectable with one or more
      monoclonal antibodies. Parallel expression of all of these features representing
      the classic MDR phenotype was observed among members of the colon and renal tumor
      panels. Certain individual cell lines among other panels (lung, ovarian,
      melanoma, and central nervous system) also manifested some aspects of the MDR
      phenotype to various extents. Identification of MDR cell lines used for large
      scale in vitro anticancer drug screening will facilitate interpretation of data
      in a way which may allow identification of new drug leads of potential value in
      treatment of MDR tumor cell populations.

PMID- 1350508
TI  - Increased expression of human ribosomal phosphoprotein P0 messenger RNA in
      hepatocellular carcinoma and colon carcinoma.
AB  - To search for differentially expressed gene products in selected cancers of
      endodermal origin, cDNA libraries derived from mRNA in human hepatocellular
      carcinoma and adjacent grossly normal tissue were generated. From these parent
      libraries, subtracted cDNA libraries of tumor minus normal and normal minus tumor
      tissues were constructed. After screening these subtracted libraries by +/-
      hybridization, a cDNA clone that is overexpressed in hepatocellular carcinoma and
      encodes the human acidic ribosomal phosphoprotein P0 (P0) was identified. We then
      evaluated the expression of this phosphoprotein P0 in human colon carcinoma
      samples. Surgical specimens of primary tumors and liver metastases were examined
      by Northern hybridization of total RNA with one of 2 32P-labeled P0 probes. The
      mRNA level of the P0 was greater in primary colon carcinoma than in paired
      adjacent normal colonic epithelium in 36 of 38 cases; the mean tumor/normal ratio
      was 2.7 (range, up to 13). The tumor/normal ratio, when plotted against the
      Dukes' stage of disease, gave evidence for increasing P0 expression with
      increasing stage of colon carcinoma (P = 0.02). In all 8 cases of paired colon
      carcinoma metastatic to liver and 2 cases of paired primary hepatocellular
      carcinoma, the P0 mRNA level was greater in tumor than in adjacent normal liver
      tissue. The mean tumor/normal ratio was 4.0 (range, up to 11) for the colon
      cancers metastatic to liver and 4.2 for the primary hepatocellular carcinoma
      samples. These findings support a common increased expression of selected gene
      products in different tumors of endodermal origin and suggest that increased P0
      expression, in line with certain other ribosomal proteins, may be associated with
      human colorectal cancer progression and biological aggressiveness.

PMID- 1350509
TI  - Sialyl Lewis(x) antigen as defined by monoclonal antibody AM-3 is a marker of
      dysplasia in the colonic adenoma-carcinoma sequence.
AB  - Monoclonal antibody AM-3 (MAb AM-3) raised against a sialomucin from human
      colorectal carcinoma has previously been shown to define a carbohydrate epitope,
      which is detectable by immunocytochemistry on all investigated colonic carcinomas
      and is expressed in correlation with the grade of dysplasia in colonic adenomas
      (Hanski et al., J. Clin. Pathol., 43: 379-385, 1990). Epitope analyses in solid
      phase enzyme immunoassays revealed that AM-3 antibody recognizes the sialylated
      Lewis(x) sequence on a branched O-linked glycan and its reductively cleaved
      alditol from human amniotic mucins. In comparative binding and binding inhibition
      studies MAbs AM-3 and CSLEX1 displayed reciprocal affinities to mucins versus
      gangliosides. Correspondingly, the weaker binding activities of AM-3 versus CSLEX
      to III3-alpha Fuc-IV3-alpha NeuAc-nLcOse4-Cer or to monogangliosides from human
      granulocytes were measured. Gangliosides from a human colon carcinoma were
      recognized by MAb CSLEX1 exhibiting a broader specificity to various sialyl
      Lewis(x) antigens and by MAb FH6 reactive to sialyl-dimeric Lewis(x) antigen, but
      not by MAb AM-3. In conclusion, MAb AM-3 is distinguished from other sialyl
      Lewis(x)-specific MAbs by its selective reactivity to mucin-carried epitopes on
      the monomeric antigen.

PMID- 1350510
TI  - Acquisition of a tumorigenic phenotype by a rat ventral prostate epithelial cell
      line expressing a transfected activated neu oncogene.
AB  - The neu oncogene has been demonstrated to be a potent transforming gene in rodent
      fibroblasts. The overexpression of the human erbB-2/neu oncogene has been
      implicated in the development and/or prognosis of several human carcinomas
      including that of the prostate. To assess the transforming potential of the
      activated rat neu oncogene in prostatic epithelial carcinogenesis, this
      laboratory has transfected a cloned non-tumorigenic, rat ventral prostate
      epithelial cell line, NbE-1.4, with an activated, point-mutated neu oncogene.
      Transfection of NbE-1.4 cells with the activated neu oncogene expression vector,
      pSV-neu-T (neu-T), resulted in an altered cell morphology, an increase in soft
      agar colony-forming efficiency, and conversion to a tumorigenic phenotype.
      Although the parental NbE-1.4 cells expressed endogenous c-neu mRNA, a reverse
      transcriptase polymerase chain reaction assay determined that the neu-T
      transfected clones expressed only the point-mutated neu-T mRNA. The suppression
      of the c-neu transcripts occurred regardless of the neu-T mRNA level expressed in
      these cell clones. These data provide evidence to show that low-level expression
      of an activated neu oncogene alone was insufficient to transform rat prostate
      epithelial cells. Rather, overexpression of an activated neu oncogene correlated
      well with the acquisition of a tumorigenic phenotype by the NbE-1.4 epithelial
      cell line.

PMID- 1350511
TI  - Ganglioside, adhesion molecule, and HLA antigen expression in basal cell
      carcinoma lesions.
AB  - The antigenic profile of basal cell carcinoma (BCC) cells was analyzed by
      immunoperoxidase staining of 27 surgically removed BCC lesions with
      antiganglioside, antiadhesion molecule, and antihistocompatibility locus antigen
      (HLA) monoclonal antibodies (MoAb). The large majority of BCC lesions were
      stained by antiganglioside MoAb; among the latter the anti-GD3 ganglioside MoAb
      R24 displayed the broadest reactivity. The GD3 ganglioside expression by BCC
      cells, which was corroborated by thin layer chromatography immunostaining with
      MoAb R24, appears to be a proliferation dependent phenomenon. Among the adhesion
      molecules tested vitronectin receptor and CDw44 were found in up to 70% of the
      lesions tested, while intercellular adhesion molecule 1 (ICAM-1) was detected in
      only a low percentage of BCC cells in one lesion. ICAM-1 was not induced on BCC
      cells in five and three lesions removed 24 and 48 h, respectively, following the
      intralesional injection of gamma-interferon. The latter enhanced HLA Class I
      antigen expression and induced ICAM-1 expression by the surrounding
      keratinocytes; furthermore gamma-interferon induced HLA Class II antigen
      expression by a small percentage of BCC cells in three lesions. These results
      suggest that malignant transformation of keratinocytes is associated with a
      selective loss of susceptibility to induction by cytokines of ICAM-1 expression.
      Besides confirming the low HLA Class I and Class II antigen expression by BCC
      cells, the present investigation has shown a differential expression of distinct
      monomorphic determinants of HLA Class I antigens and a lower expression of HLA-A
      antigens than of HLA-B antigens by BCC cells. Furthermore, the present study has
      shown that HLA Class II antigens can be induced on BCC cells by cytokines.

PMID- 1350512
TI  - Effect of a low-tryptophan diet as an adjuvant to conventional neuroleptic
      therapy in schizophrenia.
AB  - Eleven patients with DSM-III-R schizophrenia were entered into a 4-day tryptophan
      (TRP)-deficient diet. The diet lowered total plasma TRP levels in all patients;
      during the diet phase, there was a greater than 50% reduction in mean total
      plasma TRP levels from the pre-diet phase. The low-TRP diet improved performance
      on the Stroop Color and Word Test. These data are especially intriguing in view
      of the suggestion that a deficit in color-word naming is related to frontal lobe
      dysfunction and the possible occurrence of frontal lobe abnormalities in patients
      with schizophrenia. Interestingly, depressive symptomatology did not emerge on
      the TRP-deficient diet, despite the lowering of total plasma TRP levels. There
      were statistically significant improvements noted on objective ratings of the
      severity of psychotic symptomatology; however, these statistical improvements
      were without obvious clinical significance, as the magnitude of the changes on
      the behavioral ratings were minimal. The results of this study suggest that there
      might be some adjuvant potential for a low-TRP diet in the treatment of
      schizophrenia, and that schizophrenia or antipsychotic medications might offer
      some protection against the depressive effects of a TRP-deficient diet.

PMID- 1350513
TI  - Glutamatergic therapy of Huntington's chorea.
AB  - Preclinical evidence suggests that hypofunction of the glutamatergic
      subthalamopallidal tract may contribute to the hyperkinesis in Huntington's
      chorea. The clinical effects of milacemide, a glycine prodrug, were studied in
      seven patients with Huntington's disease under double-blind, placebo-controlled
      conditions. Oral doses of 1,200 mg/day did not alter chorea or cognitive
      dysfunction. Specific modulatory effects of glycine on the NMDA subtype of
      glutamate receptors, rather than the AMPA receptors, which may predominate among
      target neurons of the subthalamus, may explain the therapeutic failure of
      milacemide.

PMID- 1350514
TI  - Cytochromes c1 and b2 are sorted to the intermembrane space of yeast mitochondria
      by a stop-transfer mechanism.
AB  - The pathway by which cytochromes c1 and b2 reach the mitochondrial intermembrane
      space has been controversial. According to the "conservative sorting" hypothesis,
      these proteins are first imported across both outer and inner membranes into the
      matrix, and then are retranslocated across the inner membrane. Our data argue
      against this model: import intermediates of cytochromes c1 and b2 were found only
      outside the inner membrane; maturation of these proteins was independent of the
      matrix-localized hsp60 chaperone; and dihydrofolate reductase linked to the
      presequence of either cytochrome was imported to the intermembrane space in the
      absence of ATP. We conclude that cytochromes c1 and b2 are sorted by a mechanism
      in which translocation through the inner membrane is arrested by a "stop
      transfer" signal in the presequence. The arrested intermediates may be associated
      with a proteinaceous channel in the inner membrane.

PMID- 1350515
TI  - LEAFY controls floral meristem identity in Arabidopsis.
AB  - The first step in flower development is the generation of a floral meristem by
      the inflorescence meristem. We have analyzed how this process is affected by
      mutant alleles of the Arabidopsis gene LEAFY. We show that LEAFY interacts with
      another floral control gene, APETALA1, to promote the transition from
      inflorescence to floral meristem. We have cloned the LEAFY gene, and, consistent
      with the mutant phenotype, we find that LEAFY RNA is expressed strongly in young
      flower primordia. LEAFY expression procedes expression of the homeotic genes
      AGAMOUS and APETALA3, which specify organ identify within the flower.
      Furthermore, we demonstrate that LEAFY is the Arabidopsis homolog of the
      FLORICAULA gene, which controls floral meristem identity in the distantly related
      species Antirrhinum majus.

PMID- 1350516
TI  - Substance abuse.
AB  - The three types of drugs commonly used in sports--therapeutic drugs, performance
      enhancing drugs, and recreational drugs--have been discussed and presented in a
      way that should be helpful to health care providers dealing with athletes. The
      goal of this article has been not only to present information concerning drugs
      but also to raise the awareness level so that abuse of all types of drugs will be
      considered by athletic trainers, physicians, and health care providers when they
      deal with athletes. The role of the physician in the area of drug abuse is no
      different than the physician's role in dealing with any health problem,
      diagnosis, and management. The responsibility of the physician who deals with
      athletes always has been, is, and always will be the health and safety of the
      athlete.

PMID- 1350517
TI  - [Therapy of the adverse effects of neuroleptics].
AB  - The authors analyzed 65 women patients treated with neuroleptics and evaluated
      the results in accordance the SARS scale with regard to side-effects of the
      neuroleptic therapy. They dealt with the problem of convenience of treatment with
      antiparkinsonics to minimize side-effects of neuroleptics.

PMID- 1350518
TI  - [Analysis of RFLP haplotypes in the beta-globin gene cluster and the
      identification of beta-thalassemia genes in patients from Guangdong Province].
AB  - RFLP haplotypes of 69 chromosomes from members of 18 families affected with beta
      thalassemia (beta T) in Guangdong Province were analyzed. 17 haplotypes were
      found. Haplotypes 1, 2 and 3 accounted for most of them and 4 new haplotypes were
      identified, three of which were associated with beta T genes. In 9 families, the
      haplotype data could be used for definitive prenatal diagnosis. In 7 families,
      50% exclusive diagnosis could be achieved. In order to know the frequencies of
      various beta T genes in Guangdong Province and to improve prenatal diagnosis, we
      identified the beta T genes of 46 affected children in Guangdong Province by
      amplifying beta-globin gene sequences with the polymerase chain reaction (PCR)
      and hybridization with allele specific oligonucleotide (ASO) probes. 82 beta T
      genes hybridized with 6 probes. The most common beta T mutations were frameshift
      41/42-TCTT, -28 A----G and IVS-2 nt654 G----T, accounting for 80% of the total.
      In 36 families PCR combined with hybridization using 6 ASO probes could provide
      definitive prenatal diagnosis.

PMID- 1350519
TI  - [Analysis of RFLP haplotypes and point mutations at the phenylalanine hydroxylase
      (PAH) locus in PKU families from north China].
AB  - A study of DNA polymorphisms at the phenylalanine hydroxylase (PAH) locus was
      performed using 28 classical phenylketonuria (PKU) families from North China. In
      the families analyzed, haplotype 4 accounted for 77% of normal chromosomes and
      79% of PKU gene bearing chromosomes. Two new haplotypes, haplotypes 49 and 50,
      were found. On the basis of haplotype analysis, only 37%-40% of PKU carriers in
      North China were heterozygous and therefore informative for linkage studies. Exon
      3 (Arg111----stop) and exon 6 (Tyr204----Cys204) mutations of the PAH gene were
      studied using the polymerase chain reaction (PCR) and allele specific
      oligonucleotide probe hybridization in 42 PKU families from North China. These
      accounted for 3.6% and 9.5% of PKU mutations in North China, respectively.

PMID- 1350520
TI  - Linkage analysis and long QT syndrome. Using genetics to study cardiovascular
      disease.
AB  - BACKGROUND: Recombinant DNA technologies have facilitated the development of a
      set of polymorphic DNA markers covering the human genome. General linkage
      analysis in families predisposed to inherited disease is now feasible. Linkage
      analysis can help identify a disease gene even when relatively little is known
      about the disorder. METHODS AND RESULTS: Using this approach, we have identified
      linkage between a gene that causes the long QT syndrome and DNA markers on
      chromosome 11. CONCLUSIONS: The identification of the chromosomal location of the
      long QT locus is the first step in defining the specific mutations that cause
      this disease.

PMID- 1350522
TI  - Impact of dual-chamber permanent pacing in patients with obstructive hypertrophic
      cardiomyopathy with symptoms refractory to verapamil and beta-adrenergic blocker
      therapy.
AB  - BACKGROUND: Patients with obstructive hypertrophic cardiomyopathy (HCM) with
      symptoms refractory to drugs (beta-blockers or verapamil) are candidates for
      cardiac surgery (left ventricular septal myectomy or mitral valve replacement).
      The present study examines prospectively the ability of dual-chamber (DDD) pacing
      to improve symptoms and relieve left ventricular outflow obstruction in such
      patients. METHODS AND RESULTS: Forty-four consecutive patients with obstructive
      HCM who had failed to benefit from pharmacotherapy underwent treadmill exercise
      tests, echocardiography, and cardiac catheterization before and 1.5-3 months
      after implantation of a DDD pacemaker. Symptoms (angina, dyspnea, palpitations,
      presyncope, and syncope), New York Heart Association functional class status (1.7
      +/- 0.7 versus 3.4 +/- 0.5, p less than 0.00001), and exercise durations were
      improved at follow-up evaluation. This was associated with significant reduction
      in left ventricular outflow tract gradient (38 +/- 38 versus 87 +/- 43 mm Hg, p
      less than 0.0001) and significant increases in cardiac output and systemic
      arterial pressures. Notably, when pacing was discontinued and comparisons were
      made in sinus rhythm, treadmill exercise durations were greater and left
      ventricular outflow tract gradients were less at the follow-up evaluation
      compared with the baseline study. CONCLUSIONS: DDD pacing is an effective
      alternative to surgery in most patients with obstructive HCM with drug-refractory
      symptoms. The beneficial effects of pacing continue to be evident when pacing is
      acutely discontinued.

PMID- 1350521
TI  - Are contraction and relaxation coupled in patients with and without congestive
      heart failure?
AB  - BACKGROUND: Although changes in contractility are often accompanied by changes in
      relaxation, a mathematical model of ventricular coupling has not been described.
      A model we examined suggests a hyperbolic relation between measurements of
      contraction and relaxation. We thus tested the hypothesis that relatively load
      independent measurements of contractility (end-systolic elastance [Ees]) and
      relaxation (the slope of the tau-to-end-systolic pressure relation [R]) were
      coupled. METHODS AND RESULTS: To establish the validity of the model, an
      assessment of Ees and R was made in 30 subjects who underwent sequential digital
      ventriculography and micromanometer pressure measurements during atrial pacing
      (93 +/- 10 min-1) before and after graded doses of nitroprusside. To establish if
      a cyclic AMP (cAMP)-mediated intervention alters coupling, seven of the 30
      subjects were studied before and after 3 months of beta-blockade. To determine if
      a non-cAMP-mediated intervention alters coupling, 12 other patients were studied
      before and after deslanoside. Nonlinear regression analysis for the initial 30
      patients suggested a hyperbolic relation: (Ees) (R) = 1.05 (r = 0.79, p less than
      0.001) with an inflection point near Ees = 1.02 mm Hg/ml. Thus, with normal or
      near-normal contractility, relaxation is normal and not load dependent (R is
      close to 0). With systolic dysfunction, relaxation becomes very afterload
      dependent and so must be normalized for load. After long-term beta-blockade in
      patients with severe left ventricular dysfunction, small improvements in
      contractility (elastance) occurred with larger changes in relaxation, but the
      curve describing the relation was not displaced. Acute administration of
      deslanoside resulted in a large increase in elastance and a smaller change in
      relaxation but did not alter coupling. However, the magnitude of the change in R
      was dependent on the predrug R value. CONCLUSIONS: These data suggest contraction
      and relaxation may be physiologically coupled with relaxation relatively
      preserved in early heart failure and more rapid deterioration in relaxation as
      elastance falls under 1.02 mm Hg/ml. Both beta-blockers (which may act through
      cAMP) and digitalis (which is cAMP independent) improve contraction and
      relaxation, but both mechanisms appear to maintain coupling. The hyperbolic
      relation between contraction and relaxation may have important implications
      regarding therapeutic response and selection of patients for clinical trials in
      heart failure.

PMID- 1350523
TI  - Assay of gamma-glutamyltransferase with amino acid dehydrogenases from Bacillus
      stearothermophilus as auxiliary enzymes.
AB  - A spectrophotometric assay for serum gamma-glutamyltransferase (gamma-GT, EC
      2.3.2.2) based on the increasing absorbance at 340 nm due to NADH formation is
      described. Using gamma-glutamyl dipeptides as the donor substrate, amino acids
      formed by the gamma-glutamyl transfer from the donor substrate to the acceptor
      substrate glycylglycine are stoichiometrically converted by the corresponding
      amino acid dehydrogenases from Bacillus stearothermophilus to produce their keto
      acids and NADH. gamma-Glutamylalanine was found to be the most specific and
      sensitive donor substrate. The method can be mechanized, is free of interference
      and correlates well with conventional methods.

PMID- 1350524
TI  - Clonal heterogeneity of synovial fluid T lymphocytes in inflammatory synovitis.
AB  - Several studies have examined patients with rheumatoid arthritis for the presence
      of oligoclonal populations of synovial T lymphocytes. The results of these
      studies have been conflicting. In this study one patient with rheumatoid
      arthritis and two with other forms of inflammatory synovitis were examined by
      Southern blot analysis of T cell clones generated from synovial fluid by primary
      limiting dilution. Evidence of oligoclonality was documented only in a patient
      with psoriatic arthritis. The distinguishing characteristics of this patient, in
      addition to the diagnosis, included the fact that only one joint was involved,
      the synovitis in the affected joint was of recent onset, and the synovial fluid
      lymphocytes from which the T cells were cloned responded strongly to soluble
      antigens. Because of the association with the strong response to soluble
      antigens, synovial fluid T lymphocytes from another patient with rheumatoid
      arthritis were cloned in response to a crude mycobacterial antigenic mixture.
      Three of the seven clones examined were identical by Southern blot analysis.
      These observations suggest that the presence of oligoclonality is limited in
      patients with inflammatory arthritis. The relationship of a specific antigen
      driven response within the joint to the detection of oligoclonal T cells within
      that joint remains to be determined.

PMID- 1350525
TI  - The rising problems of asthma; mechanisms and management. Introduction.

PMID- 1350526
TI  - Basic pharmacotherapy for asthma.

PMID- 1350527
TI  - Management of respiratory failure. The rising problems of asthma; mechanisms and
      management.

PMID- 1350528
TI  - The emergent approach to asthma.

PMID- 1350529
TI  - [Modification and development of the hypothesis of transmitters in central
      nervous system in schizophrenia].

PMID- 1350530
TI  - Celiprolol--a better beta blocker?

PMID- 1350531
TI  - Mechanism of anteroposterior axis specification in vertebrates. Lessons from the
      amphibians.
AB  - Interest in the problem of anteroposterior specification has quickened because of
      our near understanding of the mechanism in Drosophila and because of the homology
      of Antennapedia-like homeobox gene expression patterns in Drosophila and
      vertebrates. But vertebrates differ from Drosophila because of morphogenetic
      movements and interactions between tissue layers, both intimately associated with
      anteroposterior specification. The purpose of this article is to review classical
      findings and to enquire how far these have been confirmed, refuted or extended by
      modern work. The "pre-molecular" work suggests that there are several steps to
      the process: (i) Formation of anteroposterior pattern in mesoderm during
      gastrulation with posterior dominance. (ii) Regional specific induction of
      ectoderm to form neural plate. (iii) Reciprocal interactions from neural plate to
      mesoderm. (iv) Interactions within neural plate with posterior dominance.
      Unfortunately, almost all the observable markers are in the CNS rather than in
      the mesoderm where the initial specification is thought to occur. This has meant
      that the specification of the mesoderm has been assayed indirectly by
      transplantation methods such as the Einsteckung. New molecular markers now
      supplement morphological ones but they are still mainly in the CNS and not the
      mesoderm. A particular interest attaches to the genes of the Antp-like HOX
      clusters since these may not only be markers but actual coding factors for
      anteroposterior levels. We have a new understanding of mesoderm induction based
      on the discovery of activins and fibroblast growth factors (FGFs) as candidate
      inducing factors. These factors have later consequences for anteroposterior
      pattern with activin tending to induce anterior, and FGF posterior structures.
      Recent work on neural induction has implicated cAMP and protein kinase C (PKC) as
      elements of the signal transduction pathway and has provided new evidence for the
      importance of tangential neural induction. The regional specificity of neural
      induction has been reinvestigated using molecular markers and provides
      conclusions rather similar to the classical work. Defects in the axial pattern
      may be produced by retinoic acid but it remains unclear whether its effects are
      truly coordinate ones or are concentrated in certain regions of high sensitivity.
      In general the molecular studies have supported and reinforced the "pre-molecular
      ones". Important questions still remain: (i) How much pattern is there in the
      mesoderm (how many states?) (ii) How is this pattern generated by the
      invaginating organizer? (iii) Is there one-to-one transmission of codings to the
      neural plate? (iv) What is the nature of the interactions within the neural
      plate? (v) Are the HOX cluster genes really the anteroposterior codings?

PMID- 1350532
TI  - LFB1 and LFB3 homeoproteins are sequentially expressed during kidney development.
AB  - LFB1 (HNF-1/HNF-1 alpha/APF) and LFB3 (vHNF-1/HNF-1 beta) are two homeoproteins
      involved in the transcriptional regulation of several liver-specific genes. Both
      genes are expressed in the polarized epithelia of a wide range of tissues,
      including liver, the digestive tract and kidney. We have analyzed the expression
      pattern of LFB1 and LFB3 in the developing rat kidney by in situ hybridization.
      Our results show that LFB3 transcripts can be detected in mesoderm-derived cells
      as soon as they are induced to differentiate into a polarized epithelium, while
      LFB1 transcripts appear only at a later stage when the three different segments
      of the nephron become apparent. LFB1 transcripts are restricted to the proximal
      and distal tubules, whereas LFB3 is also detected in the collecting ducts.
      Neither LFB1 nor LFB3 are expressed in the glomeruli or in the transition
      epithelia of the ureters and of the urinary bladder, none of which are involved
      in active transport mechanisms. The sequential activation of these two genes is
      also observed in transfilter organ cultures of nephrogenic mesenchyme at
      different stages after induction. This expression pattern suggests that LFB3 and
      LFB1 play a role in two critical stages of the developmentally regulated
      conversion of the nephric mesenchyme into a polarized epithelium: the early
      inductory phase (LFB3) and the postinductory phase (LFB1+LFB3).

PMID- 1350533
TI  - Ten different Polycomb group genes are required for spatial control of the abdA
      and AbdB homeotic products.
AB  - Mutations in genes of the Polycomb (Pc) group cause abnormal segmental
      development due to ectopic expression of the homeotic products of the
      Antennapedia and bithorax complexes. Here the requirements for Pc group genes in
      controlling the abdA and AbdB products of the bithorax complex are described.
      Embryos containing mutations in the genes Polycomb (Pc), extra sex combs (esc),
      Enhancer of zeste [E(z)], polyhomeotic (ph), Sex comb on midleg (Scm), Polycomb
      like (Pcl), Sex comb extra (Sce), Additional sex combs (Asx), Posterior sex combs
      (Psc) and pleiohomeotic (pho) were examined. In every case, both abdA and AbdB
      are expressed outside of their normal domains along the anterior-posterior (A-P)
      axis, consistent with these Pc group products acting in a single pathway or
      molecular complex. The earliest detectable ectopic expression is highest in the
      parasegments immediately adjacent to the normal expression boundary.
      Surprisingly, in the most severe Pc group mutants, the earliest ectopic AbdB is
      distributed in a pair-rule pattern. At all stages, ectopic abdA in the epidermis
      is highest along the anterior edges of the parasegments, in a pattern that mimics
      the normal abdA cell-specific pattern. These examples of highly patterned mis
      expression show that Pc group mutations do not cause indiscriminate activation of
      homeotic products. We suggest that the ectopic expression patterns result from
      factors that normally activate abdA and AbdB only in certain parasegments, but
      that in Pc group mutants these factors gain access to regulatory DNA in all
      parasegments.

PMID- 1350535
TI  - 27th Congress of the European Society for Surgical Research (ESSR). May 20-23,
      1992, Zaragoza, Spain. Abstracts.

PMID- 1350534
TI  - Is 2-propyl-4-pentenoic acid, a hepatotoxic metabolite of valproate, responsible
      for valproate-induced hyperammonemia?
AB  - To investigate the association between valproate metabolism (VPA) and VPA-induced
      hyperammonemia together with the contribution of VPA hepatotoxicity risk factors
      such as young age, polypharmacy, and high serum VPA levels to VPA-induced
      hyperammonemia, plasma ammonia (NH3) levels, serum levels of VPA and its
      metabolites, and biochemical parameters were determined in 98 patients treated
      with VPA (53 monopharmacy cases and 45 polypharmacy cases). In monopharmacy
      patients, plasma NH3 levels did not depend on age, VPA dosage or serum levels.
      Serum level of 2-propyl-4-pentenoic acid (4-en) showed a negative correlation
      with plasma NH3 level in the monopharmacy group. In polypharmacy patients, plasma
      NH3 levels, serum glutamic pyruvic transaminase, and gamma-glutamyl
      transpeptidase were significantly higher, while level/dose VPA ratio, 2-en-VPA
      serum level, and bilirubin were significantly lower than those in monopharmacy
      patients. These results suggest that young age and relatively high VPA serum
      levels within the therapeutic range were unlikely to be risk factors for common
      hyperammonemia associated with VPA therapy and that 4-en was not causally related
      to this adverse effect. The decreased serum level of 2-en-VPA in polypharmacy
      patients may be a reflection of a certain mitochondrial dysfunction, which might
      be a mechanism of the increased NH3 levels. The changes in biochemical parameters
      in polypharmacy patients were considered results of the enzyme-inducing activity
      of coadministered antiepileptic drugs (AEDs).

PMID- 1350537
TI  - IL2- and IL4-dependent proliferation of T-cell clones derived early after
      allogeneic bone marrow transplantation: studies of patients with chronic
      myelogenous leukaemia.
AB  - In an attempt to explore T-cell functions shortly after allogeneic bone marrow
      transplantation more fully, IL2- and IL4-dependent proliferation was assessed on
      CD4+ TCR alpha beta+ T-cell clones derived 4-6 weeks after transplantation. Both
      allogeneic pooled peripheral blood mononuclear cells and Epstein-Barr virus
      transformed B-cell lines (BCL) could function as accessory cells (AC) for PHA
      activation of T-cell clones. Although minimal clonal proliferation was seen when
      the T-cell activation signal was BCL+PHA+IL4, a majority of the clones could
      undergo IL4-dependent proliferation after previous activation with AC+PHA+IL2.
      For certain clones, IL4 also showed an additive effect with IL2. Thus, IL4 was a
      growth factor for a majority of the investigated posttransplant T-cell clones,
      and in vivo modulation of IL4-dependent T-cell functions may thus become a future
      therapeutic possibility to enhance graft-versus-leukaemia effects in bone marrow
      transplant recipients.

PMID- 1350536
TI  - Plasmodium falciparum: characterization of gene R45 encoding a trophozoite
      antigen containing a central block of six amino acid repeats.
AB  - We describe here an antigen, called R45, expressed by the young trophozoites of
      Plasmodium falciparum. This antigen contains a block of tandem repeats of six
      amino acids which are recognized by sera from humans living in endemic areas. The
      R45 gene is located on chromosome 3. It is present in all strains examined and
      shows limited size polymorphism. The C-terminal unique region of the protein
      shows a strong homology with the catalytic domain of the serine protein kinases.
      Interestingly, the central repeats contain a large number of putative
      phosphorylation sites. The implications of these features are discussed.

PMID- 1350538
TI  - Postterm pregnancy: computer analysis of the antepartum fetal heart rate
      patterns.
AB  - The purpose of this study was to establish reference ranges for numerical fetal
      heart rate (FHR) data in postterm pregnancy and to compare them with the patterns
      of fetuses under undisturbed condition at term. FHR was analysed on-line by
      Sonicaid Computer System 8000. A statistically significant decrease in the number
      of accelerations and decrease of variation in postterm pregnancy was observed.
      The duration of high variation (high episodes) in the 42nd week of gestation was
      statistically lower than in the pregnancy at term. These observations should be
      taken into account by clinicians in the interpretation of FHR records in postterm
      pregnancy.

PMID- 1350539
TI  - Placental malaria and pregnancy outcome.
AB  - Malaria parasitemia was assessed in 312 placentae of singleton deliveries in
      Benin. The prevalence rate was 45.19%. The dominant infecting specie was
      Plasmodium falciparum. High density parasitemia of placental smear in 44.68% was
      associated with preterm delivery, low birthweight, intrauterine growth
      retardation and neonatal mortality. Placental histological diagnosis of malaria
      in 57.69% was more frequently associated with intrauterine growth retardation.
      Extraplacental parasitemia decreased but intraplacental parasitemia increased
      with gestational age.

PMID- 1350540
TI  - Prolonged pregnancy: the management dilemma.
AB  - In a prospective randomized study, pregnancies with unfavorable cervix and well
      established gestational age of at least 42 weeks were selected for management by
      either antepartum fetal testing or prostaglandin gel induction of labor. Of the
      108 pregnancies studied, 57 (53%) had labor induced and 51 (47%) continued
      without intervention. Comparison of the two groups showed no difference in
      meconium staining, fetal distress, length of first stage of labor, the need for
      intervention, or the mode of delivery. In terms of Apgar score the neonatal
      outcome was not significantly different but a greater proportion of the babies
      (7.8% versus 1.8%) in the noninduced group required intubation. Our data show
      that there is no particular advantage in letting the pregnancy go beyond 42
      completed weeks of gestation especially if prostaglandin is available for
      induction of labor.

PMID- 1350541
TI  - The challenge of grandmultiparity in Nigerian obstetric practice.
AB  - A retrospective analysis of 733 Nigerian grandmultiparae seen at the University
      of Nigeria Teaching Hospital (UNTH) over a 3 year period was carried out. A high
      incidence of grandmultiparity (11%) was noted, and most of them (62%) belonged to
      the lower socioeconomic class. Anemia, hypertensive diseases, abruptio placentae,
      breech presentation and abnormal lie were significant complications of
      grandmultiparity. The incidence of multiple pregnancy, low birthweight babies,
      cesarean deliveries and perinatal deaths were markedly increased in the
      grandmultipara. Improvement in socioeconomic conditions of the populace, health
      education and widespread practice of family planning are suggested to reduce the
      incidence of grandmultiparity.

PMID- 1350542
TI  - Ventriculoperitoneal shunt and pregnancy.
AB  - A pregnancy in a patient with ventriculoperitoneal (VP) shunt was recently
      managed at the authors's institution. Review of the literature showed only six
      previous case reports. The management of this uncommon neurosurgical condition in
      pregnancy is presented along with a review of the literature. We conclude that
      pregnancy in a patient with a VP shunt for maternal hydrocephalus, generally has
      a normal outcome and that the function of the shunt is unaffected by pregnancy.

PMID- 1350543
TI  - A conservative surgical treatment of cervical pregnancy with active bleeding-
      uterine artery ligation and cervicotomy.
AB  - Cervical pregnancy complicated with massive bleeding usually results in abdominal
      hysterectomy, and thus the patient loses her fertility potential. Conservative
      management to control active hemorrhaging as well as to preserve reproductive
      function is necessary for women who desire more children. We present four
      patients with cervical pregnancy, complicated by life threatening hemorrhage, who
      were successfully treated with uterine artery ligation and cervicotomy.
      Subsequently, one patient had two successful term pregnancies delivered by
      cesarean section.

PMID- 1350544
TI  - Recurrent leiomyoma of the vagina.
AB  - A rare case of huge vaginal leiomyoma recurrence is reported. Vaginal leiomyoma
      is a rare entity and recurrence after its removal is extremely rare. However, if
      recurrence occurs with intact ovarian function ovariectomy should also be done.

PMID- 1350545
TI  - Intravenous leiomyomatosis with massive ascites.
AB  - A case of intravenous leiomyomatosis with massive ascites is reported. This is
      the first such recorded case. The patient was treated with a subtotal abdominal
      hysterectomy and bilateral salpingo-oophorectomy. Pathological examination
      established a vessel wall origin. There is no evidence of recurrence up to 20
      months after initial treatment.

PMID- 1350547
TI  - Proximal tubal obstruction associated with tubal schistosomiasis.
AB  - The gynecologic consequences of schistosomiasis may range from minimal
      inflammation of tubal serosa to more intense reactions involving the periadnexal
      regions. Complete obliteration of the tubal lumen has not been described. We
      describe a case of proximal tubal obstruction associated with tubal
      schistosomiasis.

PMID- 1350546
TI  - Bilateral and synchronous cervical carcinoma in situ in a didelphic uterus.
AB  - A case is reported of a bilateral and synchronous cervical squamous cell
      carcinoma in situ in a patient with uterus didelphys. Bilateral simultaneous
      conizations of both cervices were curative. Theories of tumor origin in such a
      case are discussed.

PMID- 1350548
TI  - A new nonsurgical technique for termination of intrauterine pregnancy associated
      with large multiple uterine leiomyomas.
AB  - Medical termination of a first trimester intrauterine pregnancy associated with
      large and multiple leiomyomas posed a unique problem because the sac was
      inaccessible per vaginum for surgical or vacuum evacuation. The use of
      prostaglandins was contraindicated due to a past history of bronchial asthma. But
      intraamniotic and intraplacental instillation of methotrexate, 25 mg at each
      site, under ultrasound guidance resulted in termination of pregnancy. No side
      effects or complications were observed after the procedure.

PMID- 1350549
TI  - Fatal perforation of endometriotic colon.

PMID- 1350550
TI  - Uterine tamponade-drain for hemorrhage secondary to placenta previa-accreta.

PMID- 1350551
TI  - Automobile passenger restraints for children and pregnant women. ACOG technical
      bulletin number 151--January 1991 (replaces no. 74, December 1983).

PMID- 1350552
TI  - Safety of oral contraceptives for teenagers. ACOG Committee opinion: Committee on
      Adolescent Health Care number 90--February 1991.
AB  - By age 18, 51% of adolescent women will be sexually active. Oral contraceptives
      are a safe method to avoid the potentially disastrous outcome of an unwanted
      pregnancy. The overall risks of taking oral contraceptives are much less than the
      risks of pregnancy (20). Specifically, the risks associated with the use of oral
      contraceptives by teenagers are negligible. Low-dose oral contraceptives have not
      been linked with either heart attack or stroke in contemporary U.S. studies.
      While the risk of thromboembolism in oral contraceptive users as a whole may be
      increased over that of the general population, the risk to teenagers, especially
      those who do not smoke, is minimal. The risk of death from oral contraceptive use
      for teenagers is virtually nil (12). As with all medical choices, the benefits of
      a treatment must be weighed against any potential risks. For adolescents, the
      benefits associated with the use of oral contraceptives outweight the risks,
      particularly those of pregnancy. However, teenagers at risk for sexually
      transmitted diseases should be advised to use a barrier method along with oral
      contraceptives.

PMID- 1350553
TI  - AIDS and women. World Health Organization. International Federation of Gynecology
      and Obstetrics (FIGO).

PMID- 1350554
TI  - Role of alpha-adrenoceptors in the effects of buspirone and 5
      carboxamidotryptamine in rabbit isolated thoracic aorta.
AB  - 1. The role of alpha-adrenoceptors in the vascular effects of buspirone (BUS) and
      5-carboxamidotryptamine (5-CT) was investigated in rabbit thoracic aorta. 2.
      Buspirone produced a concentration-dependent contraction. The non-selective 5-HT1
      and 5-HT2-receptor antagonist methysergide and the 5-HT2 receptor antagonist
      ketanserin did not alter the contractile effect of buspirone. However, the
      competitive antagonist of alpha 1-adrenoceptors, prazosin, shifted the
      concentration-response curve of buspirone to the right without changing the
      maximal response. 3. Benextramine tetrahydrochloride monohydrate (BHC), a
      noncompetitive antagonist of alpha 1-adrenoceptors, inhibited the contraction
      induced by buspirone in a noncompetitive manner. After pretreatment with two
      different concentrations of BHC, the estimated apparent dissociation constants of
      buspirone were found to be identical. 4. In addition, buspirone antagonized the
      concentration-response curve of phenylephrine again showing a similar
      dissociation constant, suggesting a partial agonistic action of buspirone at the
      level of alpha 1-adrenoceptors. 5. The concentration-response curve of 5-HT
      showed two components in the thoracic aorta obtained from reserpine treated and
      untreated animals as verified by different pD2 values. The second component was
      observed with relatively higher concentrations of 5-CT and could be blocked by
      prazosin or BHC. Neither of these compounds altered the first component. After
      Pretreatment with BHC, the first component of 5-CT was competitively antagonized
      by methysergide and ketanserin, having pA2 values of 8.81 and 9.1 respectively.
      6. These results suggest that the contraction induced by buspirone is mainly
      mediated by alpha 1-adrenoceptors, while the higher concentrations of 5-CT caused
      contraction via alpha 1-adrenoceptor stimulation in addition to its 5-HT2
      agonistic effect.

PMID- 1350555
TI  - Global population genetic structure and male-mediated gene flow in the green
      turtle (Chelonia mydas): RFLP analyses of anonymous nuclear loci.
AB  - We introduce an approach for the analysis of Mendelian polymorphisms in nuclear
      DNA (nDNA), using restriction fragment patterns from anonymous single-copy
      regions amplified by the polymerase chain reaction, and apply this method to the
      elucidation of population structure and gene flow in the endangered green turtle,
      Chelonia mydas. Seven anonymous clones isolated from a total cell DNA library
      were sequenced to generate primers for the amplification of nDNA fragments. Nine
      individuals were screened for restriction site polymorphisms at these seven loci,
      using 40 endonucleases. Two loci were monomorphic, while the remainder exhibited
      a total of nine polymorphic restriction sites and three size variants (reflecting
      600-base pair (bp) and 20-bp deletions and a 20-bp insertion). A total of 256
      turtle specimens from 15 nesting populations worldwide were then scored for these
      polymorphisms. Genotypic proportions within populations were in accord with Hardy
      Weinberg expectations. Strong linkage disequilibrium observed among polymorphic
      sites within loci enabled multisite haplotype assignments. Estimates of the
      standardized variance in haplotype frequency among global collections (FST =
      0.17), within the Atlantic-Mediterranean (FST = 0.13), and within the Indian
      Pacific (FST = 0.13), revealed a moderate degree of population substructure.
      Although a previous study concluded that nesting populations appear to be highly
      structured with respect to female (mitochondrial DNA) lineages, estimates of Nm
      based on nDNA data from this study indicate moderate rates of male-mediated gene
      flow. A positive relationship between genetic similarity and geographic proximity
      suggests historical connections and/or contemporary gene flow between particular
      rookery populations, likely via matings on overlapping feeding grounds, migration
      corridors or nonnatal rookeries.

PMID- 1350556
TI  - New molecular markers for the distal end of the t-complex and their relationships
      to mutations affecting mouse development.
AB  - Many mutations affecting mouse development have been mapped to the t-complex of
      mouse chromosome 17. We have obtained 17 cosmid clones as molecular markers for
      this region by screening a hamster-mouse chromosome 17 and 18 cell hybrid cosmid
      library with mouse-specific repetitive elements and mapping positive clones via t
      haplotype vs. C3H restriction fragment length polymorphism (RFLP) analysis.
      Twelve of the clones mapping distal to Leh66B in t-haplotypes are described here.
      Using standard RFLP analysis or simple sequence length polymorphism between t
      haplotypes, exceptional partial t-haplotypes and nested sets of inter-t-haplotype
      recombinants, five cosmids have been mapped in or around In(17)3 and seven in the
      most distal inversion In17(4). More precise mapping of four of the cosmids from
      In(17)4 shows that they will be useful in the molecular identification of some of
      the recessive lethals mapped to the t-complex: two cosmids map between H-2K and
      Crya-1, setting a distal limit in t-haplotypes for the position of the tw5
      lethal, one is inseparable from the tw12 lethal, and one maps distal to tf near
      the t0(t6) lethal and cld.

PMID- 1350557
TI  - Human population genetic studies using hypervariable loci. I. Analysis of
      Assamese, Australian, Cambodian, Caucasian, Chinese and Melanesian populations.
AB  - Population genetic studies, in Australian, Assamese, Cambodian, Chinese,
      Caucasian and Melanesian populations, were performed with several highly
      polymorphic DNA loci. Results showed that the Caucasian and Chinese had the
      highest level of heterozygosity. The size range of the majority of the
      polymorphic DNA fragments of a locus was the same in the different populations.
      The distinguishing feature of each ethnic group was the relative frequency of a
      particular set or group of alleles. For example, alleles greater than 9.0 kb in
      size, in D14S13, or from 4.5 to 4.7 kb, in D18S27, were less than half as
      frequent in Caucasians than in the other populations. Overall, there were groups
      of alleles, at one or more loci, whose frequencies were different among some of
      the ethnic groups and therefore could be used to differentiate one group from the
      other.

PMID- 1350558
TI  - Subtype determination of Drosophila embryonic external sensory organs by
      redundant homeo box genes BarH1 and BarH2.
AB  - BarH1 and BarH2 are two closely related homeo box genes that form a small complex
      at the Bar locus on the X chromosome of Drosophila. By immunostaining, we showed
      that BarH1 and BarH2 proteins are coexpressed in cells belonging to the central
      and peripheral nervous systems in embryos. In external sensory (es) organs, their
      expression was particularly apparent in thecogens (glial cells) and neurons at
      late development. Although deletion of BarH2 caused no appreciable morphological
      change in es organs, the simultaneous deletion of BarH1 and BarH2 led to a
      homeotic change in these organs with consequent conversion from campaniform-like
      sensilla to trichoid sensilla. In contrast, the overexpression of either BarH1 or
      BarH2 resulted in opposite morphological change. It would thus follow that BarH1
      and BarH2 are a pair of redundant homeo box genes required for the subtype
      specification of es organs.

PMID- 1350559
TI  - Mapping functional specificity in the Dfd and Ubx homeo domains.
AB  - To define homeo domain subregions that are important for embryonic targeting
      specificity of homeotic proteins, we generated a series of Deformed/Ultrabithorax
      chimeric genes in which parts of the Deformed homeo box region were substituted
      with Ultrabithorax sequences. Chimeric coding regions were attached to heat shock
      promoters and introduced into the Drosophila genome by P-element transformation.
      After heat-induced ectopic expression in embryos, we examined the cuticular
      phenotypes induced by the resulting chimeric proteins. We also tested the ability
      of the chimeric proteins to regulate transcription units that are normal targets
      of Deformed and Ultrabithorax. Our results indicate that specific amino acid
      residues at the amino end of the Ultrabithorax homeo domain are required to
      specifically regulate Antennapedia transcription; and in the context of a
      Deformed protein, these amino-end residues are sufficient to switch from Deformed
      to Ultrabithorax-like targeting specificity. Although residues in the amino end
      of the homeo domain are also important in determining a Deformed-like targeting
      specificity, other regions of the Deformed homeo domain are also required for
      full activity.

PMID- 1350560
TI  - In vivo analysis of the helix-turn-helix motif of the fushi tarazu homeo domain
      of Drosophila melanogaster.
AB  - We report a systematic mutational analysis of the helix-turn-helix motif (HTH) of
      the fushi tarazu (ftz) homeo domain (HD) of Drosophila. We started out by testing
      the function of chimeric ftz proteins containing either a part of the Sex combs
      reduced (Scr) or the muscle segment homeobox (msh) HDs. By complementation tests
      in transgenic flies, cotransfection assays in cultured Drosophila cells and in
      vitro DNA-binding assays, we have found that the ftz activity is retained in the
      ftz-Scr chimera but is lost in the ftz-msh chimera, which is defective in binding
      to an Antennapedia (Antp)-class target site. Further studies with a series of
      back-mutants of the ftz-msh chimera have revealed that a set of class-specific
      DNA backbone-contacting residues in the HTH, particularly Arg-28 and Arg-43, are
      required for efficient target site recognition and, hence, full ftz activity both
      in vitro and in vivo.

PMID- 1350561
TI  - HlA-DQalpha typing of forensic specimens.

PMID- 1350562
TI  - Terlipressin vs. somatostatin in bleeding esophageal varices: a controlled,
      double-blind study.
AB  - Fifty episodes of bleeding from esophageal or gastric varices in 33 patients with
      cirrhosis were randomized to treatment with either intravenous terlipressin (2 mg
      initially and 1 mg every 4 hr for 24 hr together with bolus injection and
      continuous infusion of placebo) or with somatostatin (250 micrograms as a bolus
      and continuous infusion of 250 micrograms/hr somatostatin for 24 hr and placebo
      injections). Standard therapy with transfusions, fluid and electrolyte correction
      and lactulose was administered in both groups. In the terlipressin group, 22 of
      25 bleeding episodes (88%) were initially stopped by the vasoactive drugs, and in
      the somatostatin group 19 of 25 bleeding episodes (76%) were initially stopped by
      the vasoactive drugs. Two of the three bleeding episodes not arrested by
      terlipressin and five of the six bleeding episodes not arrested by somatostatin
      were controlled by balloon tamponade. In one patient in each group variceal
      bleeding initially could not be stopped, and the patients died. The failure rate
      of the vasoactive treatment alone, including rebleeding episodes within the study
      period, was 20% in the terlipressin group and 32% in the somatostatin group. The
      control rate, including balloon tamponade, was 96% in both groups. The hospital
      mortality rate was 16% (4 of 25) in the terlipressin group and 24% (6 of 25) in
      the somatostatin group. Blood transfusions, use of balloon tamponade and duration
      of bleeding did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350563
TI  - Altered zonal expression of the CD26 antigen (dipeptidyl peptidase IV) in human
      cirrhotic liver.
AB  - Dipeptidyl peptidase IV is a cell surface ectopeptidase with widespread tissue
      distribution. Recently it was shown to display extracellular matrix-binding
      properties; therefore its role in cirrhosis is of interest. The aim of this study
      was to use monoclonal antibodies directed against the human CD26 antigen (which
      has been shown to be dipeptidyl peptidase IV) to study the distribution of this
      molecule in normal human and cirrhotic liver. Identical staining was obtained
      with the three monoclonal antibodies (TaI, 1F7 and TS145) and enzyme
      histochemistry. In normal liver (n = 11) intense staining of hepatic acinar zones
      2 and 3 was present, but little staining was seen in zone I. Hepatocyte staining
      was confined to the bile canalicular domain. In cirrhotic livers (n = 23)
      obtained at transplantation, staining of regenerating nodules without a zonal
      pattern was present. In addition, we saw staining of the lymphoid cell infiltrate
      and proliferating bile ductules. In a minority of cirrhotic biopsy specimens
      (four) staining of the basolateral hepatocyte domain in regenerating nodules was
      seen. Biopsy specimens from hepatic allografts (n = 28) were used as disease
      controls. These samples all showed preferential staining of zones 2 and 3,
      similar to that in normal biopsy specimens. Eleven of these samples showed
      staining of the basolateral and bile canalicular domains. In conclusion, the
      normal acinar distribution of dipeptidyl peptidase IV (zones 2 and 3) is lost in
      cirrhotic nodules. Furthermore, the altered membrane distribution of this
      molecule in cirrhosis and allograft rejection may allow increased hepatocyte
      extracellular matrix interactions during organ remodeling.

PMID- 1350564
TI  - Characterization of membrane transport mechanisms: a summary of the 1991 AASLD
      single topic conference.

PMID- 1350565
TI  - Activated type II collagen reactive T cells are not eliminated by in vivo anti
      CD4 treatment. Implications for therapeutic approaches on autoimmune arthritis.
AB  - Activation of CD4+ T cells plays an important role in type II collagen (CII)
      induced arthritis (CIA). The CD4+ T cell dependency is demonstrated by anti-CD4
      antibody treatment which suppresses CIA in mice if injected before CII
      immunization. The same anti-CD4 treatment at a later stage does not suppress CIA,
      despite extensive elimination of peripheral CD4+ T cells. A possible explanation
      for this discrepancy is that activated T cells might not be as easily influenced
      by the anti-CD4 antibodies as resting T cells. To address this question, the
      proliferative capacity of CII reactive CD4+ lymph node (LN) T cells, in mice
      treated with anti-CD4 antibodies before or after the CII immunization, was
      analyzed. In mice treated before immunization the capacity of LN cells to
      proliferate in vitro was markedly suppressed while in mice receiving anti-CD4
      treatment after immunization it was retained. Flow cytometric analysis revealed
      that the anti-CD4 treatment before and after immunization reduced the number of
      CD4+ LN T cells to the same level. The small population of CD4+ LN cells which
      were left after anti-CD4 treatment of naive mice all expressed CD44, a marker for
      previously activated T cells in mice. We propose that activation render CII
      reactive T cells more resistant to anti-CD4 treatment than virgin T cells are and
      suggest that the lack of therapeutic effect of late anti-CD4 treatment in CIA
      does not necessarily implicate that CD4+ T cells are unimportant in that stage of
      the disease.

PMID- 1350566
TI  - Murine Thy-1+ dendritic epidermal T cell lines express granule-associated
      perforin and a family of granzyme molecules.
AB  - Two T cell receptor gamma/delta + murine dendritic epidermal T cell (DETC) lines
      with cytotoxic potential towards various tumor cell lines are shown to express
      perforin and granzyme A both at the mRNA and protein levels. Furthermore, mRNA
      transcripts for granzyme B and at least one of the other granzymes D, E, F and G
      are detected in amounts equivalent to a murine IL-2-dependent alpha/beta +
      cytotoxic T lymphocyte cell line. Hemolytic granules containing serine-esterase
      (granzyme A) activity are isolated from a DETC line. Thus, cytolytically-active
      Thy-1+ DETC lines contain the granule-associated pore-forming protein, perforin,
      and at least one member of each of the three subgroups of granzyme serine
      esterases (granzyme A, B and D/E/F/G). These data support the proposed role of
      gamma/delta + DETC in immune surveillance, possibly exerting cytolytic functions
      against virus- or parasite-infected, transformed or stressed cells.

PMID- 1350567
TI  - Mechanism of MHC class I downregulation in HIV infected cells.
AB  - HIV infection of CD4+ peripheral blood lymphocytes leads to a loss of MHC class I
      molecules on the surface of the infected cells as detectable by monoclonal
      antibody staining and flow cytometry. Incubation of the infected cells at 26
      degrees C or treatment at 37 degrees C with peptides leads to upregulation of MHC
      class I to levels equal to those found on uninfected cells cultured under the
      same conditions. The data suggest that, after HIV infection, the mechanisms
      responsible for peptide generation, peptide transport and thus stable association
      between peptides and MHC class I molecules are severely affected.

PMID- 1350568
TI  - Development of the cell contact-mediated accessory function for T-cell
      proliferation in a human promyelocytic leukaemia cell line, HL-60, by 1,25
      dihydroxyvitamin D3.
AB  - A human promyelocytic leukaemia cell line, HL-60 cells, did not show accessory
      cell (AC) function to potentiate the proliferation of human T cells induced by
      anti-CD3 antibody coupled to latex beads (alpha T3-L). This was found to be at
      least due to the inability of HL-60 cells to express certain molecules which are
      inducible with interferon-gamma (IFN-gamma) on mature monocytes and are necessary
      for interaction with T cells. HL-60 cells acquired the ability to express such
      surface molecules by stimulation with IFN-gamma when the cells were pretreated
      with 1,25-dihydroxyvitamin D3 (Vit D). The effect of Vit D was reversible, that
      is, the AC function of the HL-60 cells was lost when the cells were cultured in
      Vit D-free medium for 7 days. It was also found that HL-60 cells treated with IFN
      gamma and then with Vit D did not show significant AC function. The flow
      cytometric analysis showed that the expression of HLA-DR and intercellular
      adhesion molecule-1 (ICAM-1) was highly increased on HL-60 cells when stimulated
      with IFN-gamma after treatment with Vit D. The expression of ICAM-1 was also
      induced with IFN-gamma on untreated cells but in lower amounts. Monoclonal
      antibodies against ICAM-1 and HLA-DR inhibited the alpha T3-L-induced T-cell
      proliferation, indicating that these molecules are at least required for contact
      mediated AC function. Thus our study revealed that HL-60 cells express cell
      surface interaction molecules necessary for potentiating the T-cell proliferation
      through two steps, differentiation with Vit D to mature monocyte-like cells
      followed by stimulation with IFN-gamma.

PMID- 1350569
TI  - Progressive changes in CD45RB phenotype and lymphokine production by murine CD4+
      T cells after alloantigen exposure.
AB  - Changes in CD45R expression correlate with changes in phenotype in mouse, rat and
      human T cells. It has been shown in mouse that CD45RB high T cells produce mostly
      interleukin-2 (IL-2) while CD45RB low T cells produce more IL-4 than IL-2 after
      mitogen stimulation in vitro. CD45RB expression also decreases when T cells are
      stimulated. In this study we compared responses of CD45RB high and low CD4+ T
      cells to alloantigens. Although a majority of unstimulated murine T cells from
      unimmunized mice are CD45RB high, we were able to isolate and purify sufficient
      numbers of T cells to study their response to alloantigens. When separated cells
      were stimulated in vitro with alloantigen the CD45RB high T cells became
      heterogeneous for their expression of CD45RB, indicating that high cells decrease
      their expression of CD45RB epitopes. Surprisingly, only CD45RB high T cells from
      unimmunized mice were alloreactive, as measured by proliferation and lymphokine
      secretion. In contrast, both CD45RB high and low populations from mice primed
      with allogeneic spleen were responsive to alloantigens. The 'primary' response of
      T cells from alloantigen-primed mice to third party stimulators is 10-fold
      greater in the CD45RB high population than in the CD45RB low, as would be
      predicted by our results in the primary mixed lymphocyte/leucocyte reaction
      (MLR). Furthermore, the response of CD45RB low T cells from unprimed mice and the
      response to third party alloantigen from primed mice was reconstituted by the
      addition of exogenous IL-2. The response of CD45RB low cells from primed mice was
      specific, as the third party alloresponsive cells were again primarily contained
      within the CD45RB high population. In the CD45RB high population in the secondary
      MLR we observed an increase in the production of IL-4 relative to IL-2.

PMID- 1350570
TI  - The role of T cells in pathogenesis and protective immunity to murine malaria.
AB  - T-cell-mediated immunity to a virulent strain of Plasmodium berghei NK65 (Pb
      NK65) and to an attenuated derivative (Pb XAT) of the strain were examined in CBA
      mice by the administration of monoclonal antibodies against T-cell subsets or
      interferon-gamma (IFN-gamma). The injection of anti-CD8+ or anti-IFN-gamma
      delayed the mortality of mice infected with Pb NK65, although it did not affect
      the parasitaemia. In the late stage of PB NK65 infection, T cells, especially
      CD8+ T cells, were increased in number in the liver at the expense of splenic
      CD8+ T cells. These CD8+ T cells released IFN-gamma in culture without antigen
      stimulation and were thought to induce tumour necrosis factor-alpha (TNF-alpha)
      production by the cells in the liver. In mice infected with Pb XAT, or mice
      primed with Pb XAT and then challenged with Pb NK65, CD4+ T cells had a crucial
      role in preventing parasite growth and in protective immunity. IFN-gamma was
      again the key molecule in protective immunity. These results suggest that T cells
      stimulated with malaria antigen play important roles both in protective immunity
      and pathogenesis depending upon their subsets; CD8+ T cells in pathogenesis, and
      CD4+ T cells in protective immunity. These apparently contradictory responses may
      be mediated by the same cytokine, IFN-gamma.

PMID- 1350572
TI  - Restriction fragment length polymorphism of hsp70 gene, localized in the RT1
      complex, is associated with hypertension in spontaneously hypertensive rats.
AB  - Previous studies from our laboratory have demonstrated that the intermediate
      phenotype of thermosensitivity is present in hypertensive mice and rats.
      Increased expression of hsp70 caused by increased transcription rate was
      demonstrated in vivo, in organs, and in cultured cells from spontaneously
      hypertensive rats and hypertensive mice. In this study, a polymorphism of this
      gene was revealed with BamHI enzyme by using a human hsp70 probe. A 4.4-kb
      fragment was visualized in normotensive rats (Brown-Norway BN.lx and Sprague
      Dawley), and a 3.0-kb fragment was found in spontaneously hypertensive rats (SHR)
      of three different origins and in Wistar and Buffalo rats. Both fragments were
      present in the Wistar-Kyoto rat strain. The present study mapped the polymorphism
      of hsp70 into the RT1 complex in BN.1K and SHR.1N congenic strains. The hsp70
      restriction fragment length polymorphism is associated with a blood pressure
      difference of 15 mm Hg in recombinant inbred strains. These results justify the
      search for a mechanism by which hsp70 could influence blood pressure.

PMID- 1350571
TI  - IgG subclass responses to Theiler's murine encephalomyelitis virus infection and
      immunization suggest a dominant role for Th1 cells in susceptible mouse strains.
AB  - Inbred mouse strains differ in susceptibility to Theiler's murine
      encephalomyelitis virus (TMEV)-induced demyelinating disease. A strong
      correlation between disease susceptibility and delayed-type hypersensitivity
      (DTH) has been previously demonstrated, but no strong correlation between disease
      susceptibility and total anti-TMEV ELISA titres was shown. Since both DTH and
      IgG2a antibody production are regulated by CD4+ Th1 cells, we investigated three
      strains of mice to determine whether antivirus IgG2a antibody levels, like DTH in
      previous studies, correlated with disease susceptibility. Susceptible SJL/J,
      intermediately susceptible C3H/HeJ, and resistant C57BL/6 mice were infected
      intracerebrally (i.c.) with the BeAn strain of TMEV and monitored for clinical
      signs of demyelination and for levels of TMEV-specific antibody of different IgG
      subclasses using a particle concentration fluorescence immunoassay (PCFIA).
      Resistant C57BL/6 mice were found to have significantly lower concentrations of
      total anti-TMEV antibody than susceptible SJL/J mice and intermediately
      susceptible C3H/HeJ mice show variable antibody responses. A predominance of anti
      TMEV IgG2a (Th1 regulated) antibody was seen in susceptible and intermediately
      susceptible mice, whereas resistant mice displayed a predominant anti-TMEV IgG1
      (Th2 regulated) response accompanied by a marked deficiency of IgG2a. In
      contrast, immunization of C57BL/6 mice with UV-inactivated TMEV in adjuvant
      revealed that this strain was not defective either in its ability to generate
      high levels of anti-TMEV antibody or in its ability to produce IgG2a antibody.
      These results suggest that the antivirus IgG subclass profile is dependent upon
      the immunization route, virus viability and/or the use of adjuvant and that the
      levels of antivirus subclasses may be predictive of disease susceptibility.

PMID- 1350573
TI  - Sympathetic modulation of endothelium-derived relaxing factor.
AB  - To determine whether the release of endothelium-derived relaxing factor (EDRF) is
      sympathetically mediated, we studied the effects of beta-blockade by propranolol,
      ganglionic blockade with hexamethonium, or mechanical pithing on the blood
      pressure response to EDRF inhibition in anesthetized rats. We inhibited EDRF with
      10 mg/kg of either NG-monomethyl-L-arginine (L-NMMA) or N omega-nitro-L-arginine
      methyl ester (L-NAME). In controls, L-NMMA and L-NAME increased blood pressure by
      14 +/- 1 (p less than 0.01) and 22 +/- 2 mm Hg (p less than 0.01), respectively.
      Propranolol lowered blood pressure from 98 +/- 3 to 72 +/- 4 mm Hg without
      altering the response to L-NAME (delta 26 +/- 3). This response correlated with
      the resting blood pressure (r = 0.87; p less than 0.001). Hexamethonium (25
      mg/kg) lowered blood pressure from 118 +/- 6 to 85 +/- 4 mm Hg but did not change
      the response to L-NMMA (delta 15 +/- 1). In pithed rats, blood pressure was
      lowered, but the pressor response to L-NAME was unchanged. When blood pressure
      was returned to normotensive levels by angiotensin II, norepinephrine, or
      phenylephrine, L-NAME increased blood pressure by 50 +/- 2, 68 +/- 8, and 109 +/-
      7 mm Hg, respectively (p less than 0.001). We conclude that an intact autonomic
      nervous system is not needed for the pressor response to EDRF inhibition. The
      enhanced response in pithed rats treated with vasoconstrictors may be due to
      removal of the buffering effect of the baroreceptors and the absence of EDRF,
      which would oppose vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350575
TI  - 4th European Congress on Obesity. 7-9 May 1992, Noordwijkerhout, The Netherlands.
      Abstracts.

PMID- 1350574
TI  - Characterization of natriuretic peptide receptors in cultured cells.
AB  - To elucidate physiological and clinical implications of the natriuretic peptide
      family, the expression of receptors for natriuretic peptides has been examined in
      cultured cells (a rat pheochromocytoma cell line [PC12], bovine endothelial
      cells, rat aortic smooth muscle cells, human mesangial cells, and a porcine
      kidney epithelial cell line [LLC-PK1]) by Northern blot analysis and cyclic GMP
      production method for the ANP-A and ANP-B receptors and by Northern blot analysis
      and binding assay for the clearance receptor. The ANP-A receptor was
      predominantly expressed in PC12 cells, bovine endothelial cells, and LLC-PK1
      cells but was barely expressed in rat aortic smooth muscle cells and human
      mesangial cells. By contrast, the ANP-B receptor was the major subtype of the
      biologically active receptors in rat aortic smooth muscle cells and human
      mesangial cells. Only a small amount of the ANP-B receptor was detected in PC12
      cells, bovine endothelial cells, and LLC-PK1 cells. The clearance receptor was
      abundantly expressed in rat aortic smooth muscle cells and human mesangial cells
      and was also present in bovine endothelial cells, but it was undetectable in PC12
      cells and LLC-PK1 cells. These results demonstrate that the expression of three
      natriuretic peptide receptors varies from cell to cell, which is relevant to cell
      or tissue-specific action of the natriuretic peptide family.

PMID- 1350576
TI  - Chronic rhinitis in children.
AB  - One hundred and fifty-one children aged 2-6 years old suffering from chronic
      rhinitis were followed and treated for periods of 3-6 months. Seventy-five
      children were treated with antihistamines (AH) and 76 with antibiotics (AB).
      Significant statistic difference was found between pre-school children and school
      children. The differences were both with the nature of the symptoms, and reaction
      to treatment. While 49% of the school children recovered with AH treatment, only
      14% of the pre-school children did. On the other hand, 58% of the pre-school
      children recovered with AB treatment while only 35% of the older children did.
      From our results it is clear that in many children bacterial infection is the
      cause for chronic rhinitis. In pre-school children it is the main cause, while in
      older children it is the cause in about a third of the cases. It is also
      important to remember that although allergy might be the basic reason for
      rhinitis, in certain age groups a secondary bacterial infection might interfere
      with the efficiency of antiallergic treatment.

PMID- 1350577
TI  - Neuropharmacologic and behavioral actions of clonidine: interactions with central
      neurotransmitters.

PMID- 1350578
TI  - Clinical and electromyographic evidence of carpal tunnel syndrome in a
      hypertensive patient with chronic beta-blocker treatment.
AB  - We describe a case of carpal tunnel syndrome (CTS) in a hypertensive man on long
      term treatment with a beta-blocker, propranolol. The clinical and instrumental
      findings, including MRI at the wrist, excluded all other possible causes of CTS.
      The improvement in symptoms and electromyographic findings on discontinuation of
      the drug suggested that the CTS may have been related to the beta-blocker
      therapy.

PMID- 1350579
TI  - Biosynthesis of antibiotic 1233A (F-244) and preparation of [14C]1233A.
AB  - The biosynthesis of antibiotic 1233A (F-244) was studied by feeding 13C-labeled
      precursors to the producing organism, Scopulariopsis sp. F-244. 13C NMR
      spectroscopy established that 1233A is derived from 4 methionines and 7 acetates.
      Seven acetates are condensed to form a hexaketide and 4 methyl residues from
      methionine are introduced into the main skeleton. The beta-lactone is derived
      from the alpha-carboxylic acid of the hexaketide. Since methionine was
      efficiently incorporated into 1233A, radiolabeled 1233A was prepared
      biosynthetically by feeding [14C]methionine to the producer. As a result,
      [14C]1233A was obtained with high specific radioactivity (27.2 muCi/mumols).

PMID- 1350580
TI  - Role of glutamate as the central neurotransmitter in the hypoxic ventilatory
      response.
AB  - Recent data suggest that the increase in ventilation during hypoxia may be
      related to the release of the excitatory amino acid neurotransmitter glutamate
      centrally. To further investigate this, we studied the effects of MK-801, a
      selective noncompetitive N-methyl-D-aspartate receptor antagonist, on the hypoxic
      ventilatory response in lightly anesthetized spontaneously breathing intact dogs.
      The cardiopulmonary effects of sequential ventriculocisternal perfusion (VCP) at
      the rate of 1 ml/min with mock cerebrospinal fluid (CSF, control) and MK-801 (2
      mM) were compared during normoxia and 8 min of hypoxic challenge with 12% O2.
      Minute ventilation (VE), tidal volume (VT), and respiratory frequency (f) were
      recorded continuously, and hemodynamic parameters [heart rate (HR), blood
      pressure (MAP), cardiac output (CO), pulmonary arterial pressure, and pulmonary
      capillary wedge pressure] were measured periodically. Each dog served as its own
      baseline control before and after each period of sequential VCP under the two
      different O2 conditions. During 15 min of normoxia, there were no significant
      changes in the cardiopulmonary parameters with mock CSF VCP, whereas with MK-801
      VCP for 15 min, VE decreased by approximately 27%, both by reductions in VT and f
      (17 and 9.5%, respectively). HR, MAP, and CO were unchanged. During 8 min of
      hypoxia with mock CSF VCP, VE increased by 171% associated with increased VT and
      f (25 and 125%, respectively). HR, MAP, and CO were likewise augmented. In
      contrast, the hypoxic response during MK-801 VCP was characterized by an
      increased VE of 84%, mainly by a rise in f by 83%, whereas the VT response was
      abolished. The cardiovascular excitation was also inhibited.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1350582
TI  - From abuse to violence: psychophysiological consequences of maltreatment.
AB  - This paper reviews the psychophysiological literature related to violent
      behaviors. It explores the interactions of environmental influences, pain,
      stressors, hormones, and neurotransmitters. It presents ways in which
      maltreatment in the form of abuse or neglect exacerbates preexisting
      psychobiological vulnerabilities. It proposes that whatever forces increase
      impulsivity and irritability, engender hypervigilence and paranoia, diminish
      judgment and verbal competence, and curtail the recognition of pain in the self
      and others, will enhance violence, and presents evidence that maltreatment has
      all of these effects.

PMID- 1350581
TI  - Amisulpride versus bromocriptine in infantile autism: a controlled crossover
      comparative study of two drugs with opposite effects on dopaminergic function.
AB  - An alteration of dopaminergic (DA) function much more complex than simple
      hyperactivity has been evoked in infantile autism. We therefore compared the
      clinical efficacy of a DA antagonist (amisulpride) and a DA agonist
      (bromocriptine) in a randomized, double-blind, crossover trial in 9 children with
      autism, likely severely mentally retarded. Amisulpride acts preferentially on
      specific autistic symptoms whereas bromocriptine acts more on motor hyperactivity
      and attention symptoms. These findings raise the specificity of these two drugs
      which appear to act preferentially on some target symptoms and are consistent
      with some clinical and pharmacological observations showing a sedative effect
      with low doses of DA agonists and a stimulant effect with low doses of DA
      antagonists such as the benzamides.

PMID- 1350583
TI  - Physical map of Campylobacter jejuni TGH9011 and localization of 10 genetic
      markers by use of pulsed-field gel electrophoresis.
AB  - The physical map of Campylobacter jejuni TGH9011 (ATCC 43430) was constructed by
      mapping the three restriction enzyme sites SacII (CCGCGG), SalI (GTCGAC), and
      SmaI (CCCGGG) on the genome of C. jejuni by using pulsed-field gel
      electrophoresis and Southern hybridization. A total of 25 restriction enzyme
      sites were mapped onto the C. jejuni chromosome. The size of the genome was
      reevaluated and was shown to be 1,812.5 kb. Ten C. jejuni genetic markers that
      have been isolated in our laboratory were mapped to specific restriction enzyme
      fragments. Furthermore, we have accurately mapped one of the three rRNA operons
      (rrnA) and have demonstrated a separation of the 16S and 23S rRNA-encoding
      sequences in one of the rRNA operons.

PMID- 1350584
TI  - Interaction between ribulose 1,5-bisphosphate carboxylase/oxygenase activity and
      the ammonia assimilatory system of Rhodobacter sphaeroides.
AB  - The levels of form I and form II ribulose 1,5-bisphosphate carboxylase/oxygenase
      (RubisCO) from Rhodobacter sphaeroides were found to depend on the concentration
      of ammonia supplied to photolithoautotrophically grown cultures. Under conditions
      in which the cells rapidly depleted the available ammonia, the level of in situ
      RubisCO activity decreased to less than 5% maximum activity; even at its maximum
      level under these conditions, the RubisCO activity was only 5% of the activity
      obtained from cultures supplied with saturating levels of ammonia. When cells
      were incubated with somewhat higher but not saturating amounts of ammonia, in
      situ RubisCO activity decreased immediately after the cells depleted the cultures
      of ammonia. The decrease in activity was not due to any detectable degradation of
      RubisCO protein, indicative of some mechanism to regulate the activity of the
      enzyme in response to the intracellular levels of assimilated ammonia.
      Furthermore, under conditions optimum for RubisCO inactivation, in situ RubisCO
      activity in permeabilized whole cells greatly exceeded the levels of enzymatic
      activity determined in vitro in cell extracts. Blockage of ammonia assimilation
      by inhibition of glutamine synthetase with methionine sulfoximine prevented the
      recovery of form I RubisCO from pyruvate-mediated inactivation, suggesting the
      presence of regulatory mechanisms common to both CO2 fixation and ammonia
      assimilation.

PMID- 1350585
TI  - Interaction of inactivated and active ribulose 1,5-bisphosphate
      carboxylase/oxygenase of Rhodobacter sphaeroides with nucleotides and the
      chaperonin 60 (GroEL) protein.
AB  - Purified inactivated form I ribulose 1,5-bisphosphate carboxylase/oxygenase (form
      I RubisCO) of Rhodobacter sphaeroides was activated by ATP and, to some extent,
      by other adenylates and nucleotides. Reactivation in the presence of ATP occurred
      by a time-dependent and concentration-dependent process which appeared to be
      irreversible. The carbamylated form of inactivated form I RubisCO was less
      susceptible to ATP-mediated reactivation than the uncarbamylated inactivated
      enzyme. In some cases, ATP analogs could mimic the reactivation process; one
      analog, adenylyl(beta, gamma-methylene)-diphosphonate, was found to partially
      block ATP-mediated reactivation but could not block reactivation induced by
      Mg(II). Concomitant with the recovery of enzymatic activity, the migration of the
      inactivated form I RubisCO on nondenaturing and sodium dodecyl sulfate gels
      changed from a pattern that was characteristic of inactivated enzyme to a pattern
      that was identical to that of the active protein. It was further found that
      discrete proportions of active enzyme and the chaperonin 60 protein of R.
      sphaeroides aggregated in the presence of ATP. The form I RubisCO is thus
      proposed to contain a specific ATP-binding site that may contribute to both the
      regulation of activity and the assembly of active enzyme.

PMID- 1350586
TI  - rRNA gene organization in the Lyme disease spirochete, Borrelia burgdorferi.
AB  - Lyme disease is the most common vector-borne disease in the United States. The
      causative agent is the spirochete Borrelia burgdorferi. The copy number and
      organization of the genes encoding the rRNAs of this organism were determined.
      There is a single gene for 16S rRNA and two copies each of the 23S rRNA and 5S
      rRNA genes. All of the genes are located within a chromosomal fragment of
      approximately 9.5 to 10.0 kb. The 23S and 5S rRNA genes are tandemly duplicated
      in the order 23S-5S-23S-5S and are apparently not linked to the 16S rRNA gene,
      which is situated over 2 kb upstream from the 23S-5S duplication. The individual
      copies of the 23S-5S duplication are separated by a 182-bp spacer. Within each
      23S-5S unit, an identical 22-bp spacer separates the 23S and 5S rRNA sequences
      from each other. The genome organization of the 23S-5S gene cluster in a number
      of different B. burgdorferi isolates obtained at a number of different
      geographical locations, as well as in several other species of Borrelia, was
      investigated. All isolates of B. burgdorferi tested displayed the tandem
      duplication, whereas the closely related species B. hermsii, B. anserina, and B.
      turicatae all contained a single copy of each of the genes. In addition,
      different geographical isolates of B. burgdorferi can be differentiated on the
      basis of a restriction fragment length polymorphism associated with the 23S-5S
      gene cluster. This polymorphism can be a useful tool for the determination of
      genetic relatedness between different isolates of B. burgdorferi.

PMID- 1350587
TI  - Localization of TraC, a protein involved in assembly of the F conjugative pilus.
AB  - TraC is one of the proteins encoded by the F transfer region of the F conjugative
      plasmid which is required for the assembly of F pilin into the mature F pilus
      structure. Overproduction of this protein from the plasmid pKAS2, which carries
      only traC, resulted in the formation of inclusion bodies from which soluble TraC
      was purified. When small amounts of TraC were produced from pKAS2, the protein
      was localized to the cytoplasm by using anti-TraC antibodies. Similar analysis of
      a set of TraC-alkaline phosphatase fusion proteins localized all of these fusion
      proteins to the cytoplasm. However, when TraC was expressed from the F plasmid,
      much of it appeared associated with the bacterial membrane fraction. Under these
      conditions, TraC does not appear to be part of the tip of the F pilus, as neither
      anti-TraC antibodies nor purified TraC had any effect on the infection of F
      containing bacteria by the filamentous bacteriophage f1. These data suggest that
      TraC is normally associated with the membrane through interactions with other
      proteins specified by the tra region. This interaction may be via the carboxyl
      terminal region of the TraC protein, as a mutant TraC protein containing an Arg
      Cys substitution at amino acid 811 exhibits an interaction with the membrane
      weaker than that of the wild-type protein in the presence of the other Tra
      proteins.

PMID- 1350588
TI  - A discrepancy between the instantaneous and the overall collection efficiency of
      the Fenwal CS3000 for peripheral blood stem cell apheresis.
AB  - The collection efficiency (CE) of the Fenwall CS3000 continuous flow blood cell
      separator in the apheresis of peripheral blood stem cells during haemopoietic
      recovery following myelosuppressive chemotherapy was analysed. Ninety-three
      apheresis were performed in 19 patients using procedure 3 on the Fenwal CS3000.
      The overall CE was calculated from the pre-apheresis cell counts and the stated
      blood volume processed. Instantaneous CE was calculated from cell counts in the
      inlet and return lines. The overall mononuclear cell and granulocyte-macrophage
      colony forming unit CE were 64.0% and 55.8%, respectively, significantly lower
      than the instantaneous CEs of 94.5% and 95.4%, respectively (P = 0.0001, t test,
      for both comparisons). Three factors unrelated to machine performance contributed
      to the lower overall CE despite a high instantaneous CE: (1) A fall in the
      patient's mononuclear cell counts during apheresis leading to an overestimation
      of the cells available for collection, (2) dilution of blood by anti-coagulant,
      and (3) the operational dead space of the Fenwal CS3000. The overall CE corrected
      for these 3 factors approximated the instantaneous CE closely. Thus there is
      little room for further enhancement of machine performance because the Fenwal
      CS3000 is already operating with a very high instantaneous CE. To achieve major
      improvement in the yield of peripheral blood stem cell harvests, more effective
      mobilization protocols and better timing of apheresis are required.

PMID- 1350589
TI  - No major monoclonal lymphocyte population in the thyroid of patients with Graves'
      disease: study of gene rearrangement by restriction fragment length polymorphism
      and polymerase chain reaction.
AB  - The present study aimed at determining the mono-, oligo-, or polyclonal nature of
      intrathyroid lymphocytes at the DNA level in patients with Graves' disease. Two
      techniques were used to seek monoclonal rearrangement in DNA derived from
      intrathyroidal lymphocytes obtained from six patients. The first was restriction
      fragment length polymorphism using two specific probes from the B-chain of T-cell
      receptor and the other from the heavy chain immunoglobulin gene; the second was
      polymerase chain reaction using a couple of specific primers from the variable
      and joining regions of heavy chain immunoglobulins. The results for the patients
      with Graves' disease were compared with those obtained for circulating T-and B
      lymphocytes, granulocytes (negative controls), and T- and B-leukemic cells
      (positive controls). The results with restriction fragment length polymorphism
      favored a polyclonal origin for the lymphocytes in all cases, since no
      rearrangement was visualized. The results with polymerase chain reaction were
      analogous, and the technique was 10 times more sensitive in the detection of
      rearrangement.

PMID- 1350590
TI  - Growth hormone-releasing hormone transcripts in human pituitary adenomas.
AB  - We have investigated the possibility that local production of GHRH within the
      adenohypophysis could be an aetiological factor in the development of human
      pituitary somatotroph and other tumours. We examined 51 human pituitary adenomas
      for GHRH transcripts using in situ hybridization histochemistry. GHRH transcripts
      were identified in 13 of 17 somatotroph adenomas, 4 of 10 corticotrophs, 1 of 6
      lactotrophs and 1 of 18 endocrinologically inactive adenomas. In 11 GHRH
      expressing somatotroph adenomas, SRIH transcripts were also identified. In all
      cases except one (a corticotroph adenoma) the average number of GHRH transcripts
      exceeded that found in the arcuate nucleus of simultaneously hybridized rat brain
      sections. In some pituitary adenomas, GHRH transcripts were clearly localized to
      a discrete subpopulation of cells and in these, the amount of GHRH mRNA per cell
      was comparable to that found in the GHRH-expressing cells of the rat arcuate
      nucleus. Although we have not directly demonstrated an association between the
      two, the identification of localized, high level GHRH gene expression in
      somatotroph adenomas suggests that GHRH may have a role in pituitary adenoma
      formation.

PMID- 1350591
TI  - Neurotransmitter actions in the thalamus and cerebral cortex.
AB  - The postsynaptic actions of glutamate, gamma-aminobutyric acid (GABA),
      acetylcholine, norepinephrine, serotonin, and histamine in the cerebral cortex
      and thalamus and their relevance to the control of thalamocortical activity are
      reviewed. Excitatory and inhibitory amino acids (such as glutamate and GABA) are
      proposed to form the neurotransmitters by which the executative neural networks
      of the neocortex and thalamus process synaptic information. In contrast, the more
      slowly acting neurotransmitters, acetylcholine, norepinephrine, serotonin, and
      histamine, are proposed to control the state of activity and excitability of
      thalamic and cortical neurons and thereby modulate the state of thalamocortical
      activity. Specific examples of the involvement of fast and slow transmitter
      actions in the genesis of epileptic seizures and the determination of sleep-wake
      cycles are given.

PMID- 1350592
TI  - Normal anatomy and neurophysiology of the hippocampal formation.
AB  - This article reviews the anatomy and neurophysiology of the normal hippocampal
      formation, with emphasis on the human hippocampus. The hippocampus receives
      inputs from numerous limbic, cortical, and subcortical areas, primarily via the
      entorhinal cortex and subiculum. The primary pathway of neural activity entering
      the hippocampus is from entorhinal cortex via the perforant path to the dentate
      granule cells, with collaterals to CA1 and CA3 pyramidal cells. Mossy fibers from
      granule cells excite CA3 pyramidal cells and hilar interneurons. CA3 pyramidal
      cells excite CA1 pyramidal cells, with local and commissural excitatory
      collaterals exciting other CA3 pyramidal cells and septum. CA1 pyramidal cells
      send efferent fibers to subiculum, entorhinal cortex, and several subcortical
      areas. The principal excitatory synapses are glutamatergic, with two important
      postsynaptic receptor types, alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic
      acid and N-methyl-D-aspartate. The primary inhibitory transmitter is gamma
      aminobutyric acid (GABA), with two postsynaptic receptor types, GABAA and GABAB.
      A number of modulatory transmitters and neuropeptides are also present.
      Inhibitory local synaptic networks in the hippocampus are described. Membrane ion
      channels in hippocampal neurons, particularly Ca2+ channels and K+ channels, are
      responsible for the regulation and patterning of neural activity. Long-term
      potentiation and axon sprouting are two experimental paradigms of neural
      plasticity presumably involved in hippocampal memory function.

PMID- 1350593
TI  - Subcortical structures and pathways involved in convulsive seizure generation.
AB  - Convulsive seizures in animal models usually involve one or more of the following
      components: (1) limbic motor seizures, (2) explosive running-bouncing clonic
      seizures, and (3) tonic extensor seizures. Each of these components depends on
      specific and experimentally separable anatomic substrates. Limbic motor seizures
      depend on forebrain structures for their initiation and propagation, with the
      prepiriform, piriform, and entorhinal cortices playing a prominent role in
      conjunction with hippocampus, amygdala, substantia innominata, and mediodorsal
      thalamus. In contrast, seizures involving running-bouncing clonus or tonic
      extension depend on neural substrates in the brainstem and do not appear to
      require the integrity of the forebrain for their development or expression. The
      inferior colliculus is a region from which running-bouncing seizures can be
      elicited by chemical or electrical stimulation. Tonic extensor seizures depend on
      the integrity of the nucleus reticularis pontis oralis, but a specific locus
      responsible for triggering these seizures has yet to be identified. Under
      conditions of chronic or repeated seizure activity over prolonged time periods,
      seizures evoked from the hindbrain can recruit forebrain circuits; conversely,
      repeated stimulation of forebrain limbic circuits (e.g., kindling) can modify
      susceptibility to brainstem convulsions. These long-term alterations may result
      from changes in the activity of seizure "gating" pathways, which are circuits
      that influence seizure susceptibility by modulating the threshold for the
      initiation and/or propagation of the seizures. In general, these pathways are not
      part of any core seizure propagation pathway per se. In many cases, the gating
      substrates are relatively nonselective as to the type of seizure they can
      influence. In this category, the substantia nigra and its related circuits within
      the basal ganglia serve a prominent role. In addition, ascending noradrenergic
      projections have been implicated in the regulation of seizure threshold. Other
      gating mechanisms involve thalamic circuitry and pathways originating in
      cerebellum.

PMID- 1350594
TI  - MR angiography of Takayasu arteritis.
AB  - We describe MR angiographic findings utilizing a three-dimensional time-of-flight
      technique and compare the results with angiography in a case of suspected
      Takayasu arteritis involving vessels to the neck and upper extremities.

PMID- 1350595
TI  - Proceedings Workshop on Technological Advances in Intra-oral Model Systems Used
      to Assess Cariogenicity, June 27-28, 1990 and the Consensus Conference on Intra
      oral Models, September 25-26, 1990, Chicago, Illinois.

PMID- 1350596
TI  - Attenuation of the circadian patterns of myocardial ischemia with nifedipine GITS
      in patients with chronic stable angina. N-CAP Study Group.
AB  - The Nifedipine Gastro-Intestinal Therapeutic System (GITS) Circadian Anti
      ischemia Program (N-CAP) was designed to test the effect of nifedipine GITS as
      monotherapy or in combination with a beta-adrenergic blocking agent on the
      circadian pattern of angina and silent ischemia in patients with chronic stable
      angina. At 118 sites in the United States, 1,174 patients were screened for entry
      into this study. To be eligible for participation patients were required to have
      at least two episodes of angina a week and at least two episodes of myocardial
      ischemia during 48-h ambulatory electrocardiographic (ECG) monitoring during the
      baseline placebo period. A total of 207 patients completed all phases of the
      study. Beta-blockers were continued in those patients already receiving them. In
      this 7- to 10-week single-blind placebo withdrawal study, a 1-week placebo run-in
      was followed by up to 5 weeks of single-blind titration with nifedipine GITS, a 4
      week efficacy phase with an established dose and a final single-blind 2-week
      placebo withdrawal period. Ambulatory ECG monitoring was performed at the end of
      each placebo phase and at the end of the efficacy phase with a digital monitoring
      device that was validated in a pilot study. Overall, nifedipine GITS
      significantly reduced the weekly number of anginal episodes from 5.7 to 1.8 (p =
      0.0001) and the number of ischemic events from 7.3 to 4 (p = 0.0001) reported
      during the 48-h monitoring periods, with a significant increase in both during
      the placebo withdrawal period. The baseline circadian pattern of ischemia showed
      an early morning peak and a secondary peak in the afternoon. Nifedipine GITS
      significantly reduced ischemia during the 48-h period when administered as
      monotherapy or in combination with a beta-blocker. Patients were also randomized
      to receive nifedipine GITS in either a morning or an evening dose. The two
      regimens resulted in equal anti-ischemic benefit. The primary side effect of
      nifedipine GITS was edema, which was dose related. In summary, nifedipine GITS
      reduced the number of anginal and ischemic episodes when given alone or in
      combination with a beta-blocker. Nifedipine GITS had a sustained effect: a single
      daily dose was effective over 24 h regardless of whether it was administered in
      the morning or evening. This study also suggests that combination therapy with
      nifedipine GITS and a beta-blocker is especially efficacious in reducing
      ischemia.

PMID- 1350597
TI  - Potential arrhythmogenic role of cyclic adenosine monophosphate (AMP) and
      cytosolic calcium overload: implications for prophylactic effects of beta
      blockers in myocardial infarction and proarrhythmic effects of phosphodiesterase
      inhibitors.
AB  - Activation of the adrenergic nervous system appears to play a crucial role in the
      genesis of fatal arrhythmias associated with the very early stages of acute
      myocardial infarction. The second messenger of beta-adrenergic catecholamine
      stimulation, cyclic adenosine monophosphate (AMP), has established arrhythmogenic
      qualities, acting by an increase in cytosolic calcium, which potentially has
      three adverse electrophysiologic effects. First, stimulation of the transient
      inward current by excess oscillations of cytosolic calcium can invoke delayed
      afterdepolarizations, so that triggered automaticity can develop in otherwise
      quiescent ventricular muscle. Second, cyclic AMP can evoke calcium-dependent slow
      responses in depolarized fibers, so that conditions for reentry are favored.
      Third, excess cytosolic calcium can cause intercellular uncoupling with
      conduction slowing. Focal changes in cyclic AMP and cytosolic calcium promote the
      development of ventricular fibrillation. Beta-adrenergic blockade can limit the
      formation of cyclic AMP in ischemic tissue. Furthermore, by reducing sinus
      tachycardia it can lessen cytosolic calcium overload. Hence, beta-adrenergic
      blockade helps to prevent ventricular fibrillation in the early stages of acute
      myocardial infarction and protects from sudden death in the postinfarction phase.
      In congestive heart failure, abnormalities of cytosolic calcium patterns exist
      with cytosolic calcium overload. It is proposed that the adverse effects of
      phosphodiesterase inhibitors on the mortality rate in patients with congestive
      heart failure can be explained by increased rates of formation of cyclic AMP and
      the development of calcium-dependent arrhythmias. Because calcium is the ultimate
      messenger of cyclic AMP-induced arrhythmias and because cytosolic calcium is
      increased in heart failure, it will be difficult to develop positive inotropic
      agents that are free of the risk of sudden death.

PMID- 1350598
TI  - Neurogenic cutaneous vasodilation in the cat forepaw.
AB  - The present experiments were undertaken to determine, using Laser Doppler
      flowmetry, if elimination of efferent constrictor mechanisms would unmask
      cutaneous vasodilator responses following preganglionic sympathetic nerve
      stimulation in the forepaw of anesthetized cats. We also addressed the question
      of a potential causal relationship between neurally evoked vasodilator and
      sudomotor responses. Three separate anti-adrenergic regimens were utilized: (1)
      acute guanethidine administration (1-2 mg/kg); (2) chronic monoamine depletion
      with reserpine (5 mg/kg) and alpha-methyl-para-tyrosine (2 x 300 mg/kg); and (3)
      alpha-adrenoceptor blockade with prazosin (300 micrograms/kg) and yohimbine (0.5
      mg/kg). Guanethidine treatment produced a significant depression of basal
      cutaneous blood flow whereas alpha-adrenoceptor blockade did not. In all three
      groups, stimulation of the preganglionic thoracic sympathetic nerve trunk
      produced intensity-dependent increases of digital skin blood flow along with near
      maximal sympathetic-cholinergic sudomotor (electrodermal) responses recorded
      simultaneously from the same paw. Vasodilator responses were not altered by
      intravenous propranolol (1 mg/kg) or atropine (1 mg/kg); however, evoked
      sudomotor responses were totally blocked by atropine. Low doses (1.5 mg/kg i.v.)
      of hexamethonium selectively abolished the cutaneous vasodilator responses but
      not concomitantly evoked sudomotor responses. These results demonstrate, using
      direct measurements of blood flow, that cutaneous digital vasodilation can be
      measured in cats following removal of vasoconstrictor mechanisms either pre- or
      postjunctionally. Neither muscarinic nor beta-adrenoceptor mechanisms appear to
      be involved. These experiments also suggest that cutaneous vasodilation is not a
      consequence of concomitant sudomotor activation.

PMID- 1350599
TI  - Safety aspects of outstationed laboratory equipment.

PMID- 1350600
TI  - Typing of methicillin-resistant Staphylococcus aureus with an M13 repeat probe.
AB  - A bacteriophage M13 tandem repeat has been used to probe EcoRI digested genomic
      DNA of methicillin-resistant Staphylococcus aureus (MRSA). The patterns generated
      were found to be useful in typing MRSA and generally confirmed the relationships
      that had previously been recognized in other studies based on antimicrobial
      resistance and plasmid profiles. The epidemic MRSA of London hospitals (EMRSA)
      and the majority of the epidemic MRSA of eastern Australian hospitals (EA MRSA)
      gave the same pattern. However, two isolates previously classified as EA MRSA
      gave a different pattern and a third another pattern. One isolate from Dublin,
      two isolates from Nuneaton and two isolates from Singapore gave the same pattern
      as the two EA MRSA. With the exception of the early or classic MRSA all the other
      isolates examined gave their own distinctive patterns. With one exception the
      classic MRSA belonged to a separate group. The exception was of particular
      interest because it gave the same pattern as the majority of the EA MRSA. This
      suggests that there may be an evolutionary relationship between some of the
      classic MRSA and the EMRSA of London and the EA MRSA of Australia.

PMID- 1350601
TI  - Dynamics of coagulase-negative staphylococcal colonization in patients and
      employees in a surgical intensive care unit.
AB  - Because there is little information about the frequency of carriage of various
      species of coagulase-negative staphylococci (CNS) in hospital staff, we
      prospectively investigated nasal CNS in patients and personnel in a Surgical
      Intensive Care Unit (SICU). The majority of CNS from personnel were
      Staphylococcus epidermiditis. The CNS species from patients on admission were
      more diverse and included multiply antibiotic-resistant S. haemolyticus.
      Patients' CNS became more like CNS colonizing personnel after admission with
      respect to both antimicrobial susceptibility and speciation. Plasmid and
      antibiotic sensitivity profiles of S. epidermidis resistant to multiple
      antibiotics from five patients were identified as those from one employee, but
      there was no evidence that this was of clinical significance. A variety of
      factors influence nasal colonization by CNS in SICUs. The nasal CNS of patients
      change after admission and may become more resistant and less diverse. The
      factors influencing changes in the antibiotic susceptibility and the aetiology of
      CNS infection require further study.

PMID- 1350602
TI  - Experimental pathology of intravenous polyurethane cannulae containing
      disinfectant.
AB  - Cannula tubing (1.6 mm external, 1 mm internal diameter) manufactured from
      medical grade polyurethane containing 2%, 2,4,4'-tri-chloro-2'
      hydroxydiphenylether ('Irgasan', Ciba-Geigy) was found to have no effect other
      than that seen with control ('Irgasan'-free) tubing in the following test
      systems: (i) haemolysis, (ii) endothelial cell cultures, (iii) paravertebral
      muscle of rabbits, (iv) jugular vein of rabbits, (v) cannulation of baboons and
      (vi) clotting times of human platelet-rich plasma. However, the results from (iv)
      showed a significant amount of damage from both inpregnated and control cannulae
      and (v) showed that all detectable 'Irgasan' had been eluted from the portions of
      tubing retained within the animal before the end of the experiment, more rapidly
      than predicted from in-vitro studies. The rate of elution of 'Irgasan' in vivo
      needs to be further investigated, and consideration should be given to developing
      a plastic-disinfectant combination with a slower rate of loss of disinfectant.

PMID- 1350603
TI  - Epidemiology of reported sharps injuries in a tertiary care hospital.
AB  - Over a 12-month period 233 puncture wounds were reported in a 1112-bed tertiary
      medical care centre. Accident forms were reviewed to determine the epidemiology
      of puncture injuries. The nursing department accounted for the majority of all
      puncture injuries (68%). For nurses, medical and surgical units represented those
      clinical areas with the greatest number of puncture injuries. Areas with the
      highest incidence rates, however, included the clinical research centre, the
      emergency room, the surgical intensive care unit and areas where the intravenous
      team operated. Activities involving direct contact of a sharp instrument with a
      patient accounted for the majority of puncture injuries. Disposable syringes and
      loose needles were implicated in 50% of injuries although the incidence of injury
      per individual's low (3.2 out of 100,000 purchased). Recommendations include the
      redesigning of sharp instruments and the focusing of education programmes to
      target personnel for whom incidence rates are the highest.

PMID- 1350604
TI  - Epidemiological role of arthropods detectable in health facilities.
AB  - A total of 161 arthropod specimens were collected from 55 sites in a health care
      facility during July and September 1990. Of the 116 bacterial isolates obtained
      from their body surfaces 6% were from parasites (mosquitoes), 59% from
      eusynanthropic arthropods (Tenebrionid beetles, flies, German cockroaches,
      wasps), 16% from hemisynanthropic arthropods (ants, spiders) and 19% from
      occasionally encountered insects (non-biting midges, moths, beetles). Most (88%)
      of the isolated bacteria were Gram-negative rods of the species E. coli,
      Enterobacter, Klebsiella, Citrobacter, Proteus, Serratia, Pseudomonas and
      Acinetobacter. Gram-positive cocci accounted for 13% of isolates and were
      primarily represented by coagulase-negative staphylococci. The highest isolation
      rates were from body surfaces of flies, German cockroaches, non-biting midges
      (Chironomids) and Tenebrionid beetles. About one third of all isolates were
      resistant to more than three antimicrobials using a standard disc diffusion
      assay. The presence of multiple resistance to antibiotics was observed in two
      thirds of Enterobacter isolates, namely those of Enterobacter cloacae from the
      body surface of Germany cockroaches, in 13% of Citrobacter spp and in 8% of
      Klebsiella spp as well as Acinetobacter calcoaceticus strains. Strains of
      Morganella and Hafnia species were very infrequent but all of them shared
      resistance to the antibiotics tested. In contrast, strains of Serratia spp were
      relatively antibiotic-sensitive. The group of isolated Gram-positive organisms
      was represented by two strains of Staphylococcus hominis and one strain of
      Enterococcus sp, all of them were multiply-resistant to antimicrobials.

PMID- 1350605
TI  - Flavimonas oryzihabitans (CDC group Ve-2) bacteraemia associated with Hickman
      catheters.
AB  - Flavimonas oryzihabitans is a potential pathogen that may infect patients who
      have major medical illnesses, especially those who are undergoing surgery or have
      indwelling venous catheters in situ. Flavimonas oryzihabitans has been isolated
      from a wide range of body sites, and the portals of entry are major wounds or
      implanted foreign materials. We report two cases of F. oryzihabitans bacteraemia
      associated with the use of Hickman catheters for administration of the patients'
      chemotherapeutic agents. However, a common source for these infections could not
      be demonstrated.

PMID- 1350606
TI  - Assessment of risk of microbial contamination by use of multidose containers of
      injectable products.
AB  - At a vaccination centre 200 emptied multidose vials were tested for sterility.
      All vials had contained 10 doses of a vaccine without added preservative. None of
      the 200 vials was culture-positive. The vaccine did not comply with the
      pharmacological test for effectiveness of antimicrobial preservatives.

PMID- 1350607
TI  - Ultraviolet radiation effects on human keratinocyte ICAM-1 expression: UV-induced
      inhibition of cytokine-induced ICAM-1 mRNA expression is transient,
      differentially restored for IFN gamma versus TNF alpha, and followed by ICAM-1
      induction via a TNF alpha-like pathway.
AB  - Human keratinocytes (KC) during the course of inflammatory dermatoses strongly
      express the surface molecule ICAM-1, which plays an important role in the
      generation of the epidermal inflammatory infiltrate by mediating leukocyte
      keratinocyte interactions. Accordingly, KC ICAM-1 expression is known to be
      induced in vivo and in vitro by cytokines either via the TNF alpha/TNF beta or
      via the IFN gamma-mediated pathway. In contrast, ultraviolet (UV) radiation
      previously has been found to potently inhibit cytokine-induced KC ICAM-1 surface
      expression by a sublethal mechanism. In order to further define this novel
      immunosuppressive effect of UV light, the effects of in vitro UV radiation on
      ICAM-1 mRNA expression in transformed human KC (KB cells) were examined.
      Accordingly, UV light (0-100 J/m2) inhibited IFN gamma- as well as TNF alpha
      induced ICAM-1 mRNA expression, if KC were cytokine stimulated immediately after
      irradiation. After a 12-h incubation period, however, IFN gamma responsiveness
      was found to be restored in irradiated cells, whereas restoration of
      responsiveness to TNF alpha required at least a 24-h recovery phase. Moreover, UV
      light alone did not alter ICAM-1 mRNA levels after 4, 12, or 24 h. After 48 h,
      however, a significant increase in ICAM-1 mRNA and surface expression in UV
      irradiated KC could be observed. In addition, this increase could be superinduced
      by stimulation of irradiated KC with IFN gamma, but not with TNF alpha. UV
      induced upregulation of ICAM-1 expression could be mimicked by stimulating
      unirradiated cells with supernatants derived from UV-irradiated cells. Addition
      of biologically active anti-TNF alpha antibodies to UV-irradiated cells or to
      supernatants derived from UV-irradiated KC, however, did not even partially
      abolish this ICAM-1-inducing activity. UV light thus seems to affect KC ICAM-1
      mRNA expression in a biphasic manner: an early period of inhibition of cytokine
      induced ICAM-1 expression is transient and followed by restoration of
      responsiveness to ICAM-1-inducing cytokines. Moreover, UV itself is able to
      induce ICAM-1 mRNA expression at this later time point via a TNF alpha-like
      pathway. These studies identify UV irradiation as a potent modulator of cytokine
      regulated ICAM-1 gene transcription with the capacity to induce both inhibitory
      as well as enhancing effects.

PMID- 1350608
TI  - CD4 antibody therapy and cyclosporin A differentially affect HLA-DR and ICAM-1
      expression in psoriatic skin.

PMID- 1350609
TI  - [Sea urchin sperm-activating peptide: structure, biosynthesis and action
      mechanism].

PMID- 1350610
TI  - Role of oxygen-derived free radical scavengers in the management of recurrent
      attacks of ulcerative colitis: a new approach.
AB  - This double-blind, randomized study investigated the role of oxygen-derived free
      radical scavengers in the management of recurrent attacks of ulcerative colitis.
      To this end, allopurinol (50 mg four times a day) and dimethyl sulfoxide (500 mg
      four times a day) were administered orally. Patients with recurrent attacks of
      moderate proctosigmoidal ulcerative colitis, in spite of prophylaxis with orally
      administered sulfasalazine (2 gm daily), were given 10 mg prednisolone by mouth
      four times a day; 500 mg sulfasalazine by mouth four times a day; and morning and
      evening retention steroid enema (Predsol, 20 mg) alone or with allopurinol or
      dimethyl sulfoxide. After 2 weeks of treatment with sulfasalazine and
      prednisolone alone, 51% of patients (n = 45) were free of symptoms. Addition of
      allopurinol (n = 46) or dimethyl sulfoxide (n = 45) to the mentioned regimen
      controlled the symptoms within 2 weeks in 84% of patients (p less than 0.01).
      During 12 months of prophylactic treatment, 5% of patients (n = 42) who were
      given sulfasalazine (2 gm daily) and allopurinol and 5% of patients (n = 40) who
      were given sulfasalazine (2 gm daily) and dimethyl sulfoxide relapsed compared
      with 25% of patients who were given sulfasalazine (2 gm daily) alone (p less than
      0.05). The results suggest that oxygen-derived free radicals may be involved in
      the mechanism of ulcerative colitis and that removing them may be useful in the
      treatment of attacks and in protecting the colon against recurrence of attacks.

PMID- 1350611
TI  - Hemophilia A carrier detection by restriction fragment length polymorphism
      analysis and discriminant analysis based on ELISA of factor VIII and vWf.
AB  - We performed carrier determination on female subjects from 32 hemophilia A
      kindreds with a combination of restriction fragment length polymorphism analysis
      and discriminant analysis of factor VIII antigen and von Willebrand factor
      antigen analyzed by enzyme-linked immunosorbent assay. Subjects included 25
      obligate carriers, 30 at-risk female subjects from 19 kindreds each with two or
      more male subjects, with hemophilia and 28 at-risk female subjects from 13
      kindreds each with a single sporadic case. Deoxyribonucleic acid (DNA) analysis
      with factor VIII intragenic probes clarified the carrier status of 15 female
      subjects, and extragenic probes classified an additional 14. Discriminant
      analysis, which identified 24 of 25 (96%) obligate carriers with carrier
      probabilities greater than or equal to 0.71 and 37 of 39 (95.0%) normal female
      subjects with probabilities less than or equal to 0.30, was useful for clarifying
      the carrier status of the female subjects who were not helped by DNA analysis and
      those that were classified by extragenic probes alone. Twenty-nine female
      subjects could not be categorized by restriction fragment length polymorphism
      analysis because DNA was unavailable from the subject or from key family members,
      key female subjects were noninformative, or carriership could not be excluded by
      restriction fragment length polymorphism in kindreds with sporadic cases. We
      studied 28 of these female subjects by discriminant analysis; 15 had carrier
      probabilities of greater than or equal to 0.71, 12 less than or equal to 0.30,
      and 1 = 0.35. All carriers by extragenic probes had carrier probability values
      greater than or equal to 0.71, whereas all noncarriers had values less than or
      equal to 0.30. In some families, particularly those in which gonadal mosaicism
      was a possibility, extensive family studies together with DNA and discriminant
      analyses were required for clarifying the source of the mutation, and hence the
      carrier status of the at-risk female subjects. Thus DNA and discriminant analyses
      complement each other, and when combined with careful pedigree analysis, the
      power of carrier determination is increased in some families.

PMID- 1350612
TI  - Analysis of the clonal relationships between strains of Neisseria meningitidis by
      pulsed field gel electrophoresis.
AB  - Fingerprint patterns were generated from strains of Neisseria meningitidis by
      digestion of chromosomal DNA samples with 'rare-site' restriction endonucleases
      and resolution of the resultant fragments by pulsed field gel electrophoresis
      (PFGE). The potential of this technique for the rapid establishment of the clonal
      relationships between different isolates of the meningococcus was investigated.
      The fingerprint patterns from various serogroup A strains, previously assigned to
      clonal subgroups on the basis of their electrophoretic types (ETs), were
      compared. Fingerprints generated with the endonucleases SfiI, SpeI and NheI each
      gave distinctive patterns for the clonal subgroups I-IV of serogroup A. Further,
      the endonucleases SpeI and, particularly, NheI were capable of resolving
      differences between various subgroup III strains isolated at different times and
      geographical locations. Strains isolated during the 'new wave' pandemic, which
      was associated with the Haj, from Europe, America, and Africa, had a
      characteristic fingerprint pattern and appeared to be distinct from 'old wave'
      pandemic strains. The PFGE technique is a relatively rapid and sensitive method
      for establishing clonal relationships among epidemic strains of N. meningitidis.

PMID- 1350613
TI  - Phenomenology and sequelae of 3,4-methylenedioxymethamphetamine use.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) has been at the center of a debate over
      its potential benefits as an adjunct to psychotherapy versus its capability for
      neurotoxic effects and is currently classified as a Schedule 1 drug by the Drug
      Enforcement Administration (DEA). However, as yet, there is very little
      methodological data on the subjective experience of the MDMA-induced state or its
      psychological and behavioral sequelae. The present study was, therefore, designed
      to obtain this kind of information. Twenty psychiatrists who had taken MDMA
      previously were evaluated using a semistructured interview. Subjective experience
      of the actual MDMA-induced state, as well as both short-term (less than 1 week)
      and relatively longer term (greater than 1 week) sequelae, were examined
      retrospectively. Side effects, insight gained, pleasure, and intensity of the
      MDMA experience were evaluated as were the influence of set and setting at the
      time the MDMA was taken and the dosage utilized. Finally, the authors discuss
      methodological problems and limitations of a study of this type.

PMID- 1350614
TI  - The MDMA-neurotoxicity controversy: implications for clinical research with novel
      psychoactive drugs.

PMID- 1350616
TI  - Hypertension in the elderly: focus on risk factors. The Second International
      Congress. 5-7 December 1990, Rome, Italy.

PMID- 1350615
TI  - Four new bioactive polyhydroxylated sterols from the black coral Antipathes
      subpinnata.
AB  - Four new polyoxygenated sterols 2-5 were isolated from the marine black coral
      Antipathes subpinnata. The structures of these compounds, including
      stereochemical details, were deduced by ms, 1H- and 13C-nmr, 1H-1H COSY, and nOe
      difference spectroscopy. Compounds 2-5 are lethal to brine shrimp (Artemia
      salina).

PMID- 1350617
TI  - Plasma gastrin-34 increases during and immediately after breast-feeding in 3-day
      old infants.
AB  - We examined whether plasma gastrin concentration increases during breast-feeding
      in infants. The peptide concentration was measured cross-sectionally before,
      during, and after breast-feeding in healthy, 3-day-old infants (n = 72).
      Somatostatin, a modulator of gastrin release, was also analyzed. Both peptides
      were measured by radioimmunoassay and were further characterized by high
      performance liquid chromatography (HPLC). The (mean +/- SD) concentration of
      gastrin rose significantly from 63 +/- 24 pmol/L before feeding to 92 +/- 32
      pmol/L (p less than 0.01) and 95 +/- 21 pmol/L (p less than 0.01), 5 and 10 min
      after the initiation of sucking, respectively. The gastrin concentration was 102
      +/- 35 pmol/L (p less than 0.01) immediately after feeding. Plasma somatostatin
      concentration was unaffected by feeding. As assessed by HPLC, circulating gastrin
      before, during, and after feeding was found to correspond to gastrin-34, whereas
      circulating somatostatin was found to correspond to somatostatin-14. We conclude
      that in contrast to earlier studies, plasma gastrin concentration increases
      during and immediately after breast-feeding in infants.

PMID- 1350618
TI  - XIIIth European Congress of Perinatal Medicine, Amsterdam, May 12-15, 1992.
      Abstracts.

PMID- 1350619
TI  - Illicitly imported heroin products (1984 to 1989): some physical and chemical
      features indicative of their origin.
AB  - Samples taken from seizures of imported illicit heroin preparations of known
      geographical origin have been examined. The typology developed in two previous
      surveys of illicit heroin products is applicable to many of the samples studied
      in this work, although significant changes have occurred in the chemical profile
      of illicit heroin products from certain geographical regions. It remains
      possible, however, to give an opinion as to the origin of many samples of illicit
      heroin of unknown provenance. The observation in the previous surveys that
      unrelated samples of illicit heroin possess unique chemical profiles has been
      confirmed by the present results.

PMID- 1350620
TI  - Accumulation of polyvinylpyrrolidone within the inflamed paws of adjuvant-induced
      arthritic rats.
AB  - 125I-Labelled polyvinylpyrrolidone ([125I]PVP) of a range of molecular weights
      (mol. wt 10, 40 and 360 kDa) was injected i.v. into adjuvant-induced arthritic
      and normal rats and the blood clearance and tissue distribution of the polymers
      determined. The half-life of PVP in the circulation increased with increasing
      mol. wt; 10, 40 and 360 kDa polymers had mean terminal half-lives of 2.2, 6.9 and
      16.4 h, respectively. Tissue uptake was also found to be mol. wt dependent, the
      largest PVP molecule accumulating to a greater extent in the spleen, liver, lungs
      and paws in both normal and arthritic rats (P less than 0.01) than the two lower
      mol. wt polymers. Accumulation of the polymer in inflamed paws (g tissue)-1
      greatly exceeded that of normal paws (P less than 0.01). This difference was
      particularly noticeable with 360 kDa PVP, where arthritic paws amassed 7 times
      more PVP than normal paws.

PMID- 1350621
TI  - The effect of dinoprost on transport of water and imipramine through rat small
      intestinal membranes.
AB  - The relation between transmucosal fluid movement and its effect on absorption and
      exsorption of imipramine was studied with the in-situ single-pass perfusion
      technique in rats. Dinoprost (prostaglandin F2 alpha, PGF2 alpha) caused a dose
      related inhibition of both absorption and secretion of water across the
      intestinal membrane. When PGF2 alpha was infused at a rate of 5 mumols kg-1 h-1,
      the absorption rate of water decreased from 51.7 to 21.5 mL h-1 and the secretion
      rate decreased from 48.9 to 26.8 mL h-1. Net water flux changed from net water
      absorption (0.9 mL h-1) to net water secretion (5.33 mL h-1) by infusion of PGF2
      alpha. However, absorption and exsorption of imipramine were little affected by
      infusion of PGF2 alpha. The absorption rates of imipramine were 3.03 and 2.36 mg
      h-1 in the absence and presence of PGF2 alpha, respectively. Furthermore, the
      average amounts of imipramine exsorbed into the intestinal lumen in 2 h were 7.82
      and 8.10% in the absence and presence of PGF2 alpha, respectively. Infusion of
      PGF2 alpha also enhanced motility of the small intestine compared with the
      control. From these results, it appears that PGF2 alpha has no effect on the
      absorption and exsorption of imipramine across the intestinal membrane although
      it is reasonable to use PGF2 alpha in the case of patients with overdoses of
      drugs which decrease gastrointestinal motility.

PMID- 1350622
TI  - Opioid properties of some isomeric derivatives of phencyclidine.
AB  - The phencyclidine analogues (+/-)-alpha-, (+/-)-beta-, and (+)-alpha- and and (-)
      alpha-4-hydroxy-3-methyl-4-phenyl-1-(1-phenylcyclohexyl)piperidine, all with
      known relative and absolute stereochemistry, have been prepared, and their
      analgesic potencies related to corresponding prodines. In contrast to the
      prodines, the (+/-)-alpha-phencyclidine analogue was a more potent analgesic than
      its diastereoisomer, while in agreement with observations in the prodine series,
      the 3R,4S-alpha-enantiomer displayed substantially greater potency than its
      mirror image form.

PMID- 1350623
TI  - Alpha 2-adrenoceptor changes during cerebral ageing. The effect of Ginkgo biloba
      extract.
AB  - [3H]Rauwolscine binding to alpha 2-adrenoceptors in cerebral cortex and
      hippocampus membranes of young (4 months) and aged (24 months) Wistar rats has
      been investigated. In aged rats, Bmax values of [3H]rauwolscine binding were
      significantly reduced (25-32%) in the cerebral cortex and hippocampus, as
      compared with the number of alpha 2-adrenoceptors found in young rats. Chronic
      treatment with Ginkgo biloba extract did not alter [3H]rauwolscine binding in the
      hippocampus of young rats, but significantly increased (28%) the [3H]rauwolscine
      binding density in aged rats. These data confirm the previously described age
      related noradrenergic alteration and suggest that noradrenergic activity in aged
      rats is more susceptible to Ginkgo biloba extract treatment.

PMID- 1350624
TI  - Investigation of the interaction mode of phenothiazine neuroleptics with alpha 1
      acid glycoprotein.
AB  - The interaction of phenothiazine neuroleptics with alpha 1-acid glycoprotein
      (AGP) and desialylated AGP (asialoAGP) has been investigated by fluorescence,
      circular dichroism spectroscopy and by equilibrium dialysis. The binding
      parameters of phenothiazines obtained from fluorescence agreed closely with those
      obtained from circular dichroism and equilibrium dialysis. The binding affinities
      (nK) to AGP were slightly higher than binding affinities to asialoAGP. Attempts
      to correlate binding affinities with partition coefficients suggested that
      hydrophobic forces were mainly involved in the binding of phenothiazine
      neuroleptics to AGP and asialoAGP. However, electrostatic interaction was also
      found to be involved as suggested by experimental data obtained from the
      influence of oleic acid and caesium chloride on the drug binding to the two
      proteins.

PMID- 1350625
TI  - Effects of anaesthetic agents on pressor response to beta-blockers in the rat.
AB  - It has been shown that paradoxical pressor response to a beta-adrenoceptor
      antagonist occurs in conscious rats pretreated with an alpha-adrenoceptor
      antagonist. This study examines the influence of anaesthetic agents on mean
      arterial pressure (MAP) response to a beta-blocker. Cumulative dose-response
      curves of propranolol (non-selective), ICI 118,551 (beta 2-selective) and
      atenolol (beta 1-selective) were constructed in phentolamine-treated rats
      anaesthetized with urethane, pentobarbitone or halothane. I.v. injections of all
      three beta-blockers caused dose-dependent increases in MAP in urethane
      anaesthetized rats. In halothane-anaesthetized rats, propranolol and atenolol did
      not alter MAP while ICI 118,551 caused a small dose-dependent increase in MAP. In
      the presence of pentobarbitone, none of the beta-blockers raised MAP. In the
      second series of experiments, a single i.v. bolus dose of propranolol was given
      in phentolamine-treated rats anaesthetized with pentobarbitone, amobarbitone,
      ketamine or chloralose. Propranolol did not affect MAP in rats anaesthetized with
      pentobarbitone, amobarbitone and chloralose but it partially reversed the
      hypotensive effect of phentolamine in ketamine-anaesthetized rats. In the third
      series, propranolol or atenolol was i.v. injected in pentobarbitone-anaesthetized
      rats treated with both phentolamine and adrenaline. Both propranolol and atenolol
      raised MAP. Our results show that anaesthetic agents differentially affect the
      MAP response to a beta-blocker.

PMID- 1350627
TI  - The optical resolution of racemic chlorpheniramine and its stereoselective
      pharmacokinetics in rat plasma.
AB  - An ovomucoid-conjugated column has been developed for the chiral stationary-phase
      liquid chromatographic resolution of racemic chlorpheniramine with a quantitation
      limit of 0.05 microgram mL-1. The assay was used to study the stereoselective
      kinetics of chlorpheniramine enantiomers in rats. After bolus intravenous
      administration of racemic chlorpheniramine maleate (20 mg kg-1), plasma
      concentration of the (-)-form was higher than that of the (+)-form. In the
      elimination phase, the concentrations of (+)- and (-)-chlorpheniramine in the
      plasma declined biexponentially with half-lives of 18.2 and 50.0 min,
      respectively. Although there was no significant difference in blood-to-plasma
      concentration ratio of both enantiomers, the apparent total blood clearance of
      (+)-chlorpheniramine was twice as large as that of the (-)-isomer. Binding of (-)
      chlorpheniramine to rat plasma protein was stronger than that of (+)
      chlorpheniramine suggesting stereoselective pharmacokinetics may be due to a
      difference in the plasma protein binding.

PMID- 1350626
TI  - Diuretic action of the novel loop diuretic torasemide in the presence of
      angiotensin II or endothelin-1 in anaesthetized dogs.
AB  - The effects of torasemide (0.1 and 1 mg kg-1, i.v.) and furosemide (3 mg kg-1) on
      renal haemodynamics and excretory responses in the presence of angiotensin II and
      endothelin-1 was examined in anaesthetized dogs. Angiotensin II or endothelin-1
      was continuously infused into the renal artery throughout the experiment and a
      bolus of torasemide or furosemide was injected into the bracheal vein. Continuous
      intrarenal arterial (i.r.a.) infusion of angiotensin II, at a dose of 5 ng kg-1
      min-1, increased renal vascular resistance (RVR) and decreased renal blood flow
      (RBF) and glomerular filtration rate (GFR), but had no effect on systemic mean
      arterial pressure (MAP). Urinary excretion of sodium (UNaV) and urine flow (UF)
      were significantly decreased during angiotensin II infusion. Intravenous
      injections of torasemide in the presence of angiotensin II caused a dose
      dependent increase in UF, UNaV and urinary excretion of potassium (UKV), while a
      decrease in RVR was accompanied by an increase in RBF. UKV was greater in the
      furosemide group than in the torasemide group, despite both groups having the
      same degree of aquaresis and natriuresis. Continuous i.r.a. infusion of
      endothelin-1, 1.5 ng kg-1 min-1, produced effects similar to those of angiotensin
      II on renal haemodynamics; however, the onset of action was extremely slow
      compared with the effects produced by angiotensin II. Endothelin-1 caused a
      significant decrease in UF, UNaV and UKV only at a later period, despite a
      relatively early depression of renal haemodynamics. Torasemide and furosemide
      also produced a sufficient diuretic action in this model.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1350628
TI  - Method for analysis, and distribution profile, of covalently-linked ferritin
      daunorubicin conjugate in the blood of trypanosome-infected mice.
AB  - Daunorubicin is a highly potent trypanocide in-vitro but is inactive in-vivo.
      When daunorubicin is conjugated to bovine serum albumin or horse spleen ferritin
      using Schiffs base linkages, the complex is trypanocidal in-vitro and in-vivo. We
      have developed novel analytical methods, using HPLC with fluorimetric detection,
      for the quantitation of daunorubicin and doxorubicin in biological samples,
      either as unconjugated drug, or when covalently linked to macromolecules or
      particles. Ferritin-daunorubicin conjugate (25 mg kg-1) was administered
      intraperitoneally to mice infected with monomorphic Trypanosoma brucei
      rhodesiense; peak plasma levels occurred after 1.5 h, and were 5 times higher
      than those resulting from administration of an equivalent amount of unconjugated
      daunorubicin. Plasma levels then declined rapidly (t1/2 for 1-6 h period was 0.58
      and 0.86 h respectively for conjugated and unconjugated daunorubicin). However,
      higher plasma levels were seen 24 h after treatment, suggesting the distribution
      profile of daunorubicin when conjugated to ferritin is multiphasic with resultant
      high levels of daunorubicin obtained for a prolonged time period.

PMID- 1350629
TI  - The influence of beta-cyclodextrin on the solubility and dissolution rate of
      paracetamol solid dispersions.
AB  - The effect of cyclodextrin (beta-CD) on the solubility and dissolution rate of
      various paracetamol dispersion powders (1:1 w/w), and tablets was studied. Lower
      solubility was exhibited by a spray dried solid dispersion made from paracetamol
      Ethocel-Macrogol 6000 (95:2:3). The improvement in solubility was influenced by
      complexation with beta-CD and the crystalline nature of the powder products made
      by different procedures. The difference in crystallinity was confirmed by X-ray
      powder diffraction patterns. The dissolution rate of paracetamol from tablets
      made from the solid dispersions was satisfactory compared with paracetamol alone.
      The differences between the dissolution rate from the examined paracetamol
      tablets resulted from the different solubility of each powder and from the
      structural changes of particles which influenced the consolidation of the tablet
      mass.

PMID- 1350630
TI  - Salivary excretion of mexiletine after bolus intravenous administration in rats.
AB  - Salivary excretion of mexiletine was investigated following bolus intravenous
      administration (10 mg kg-1) in rats. Parotid and mandibular saliva was collected
      separately by stimulating salivation with constant rate infusion of pilocarpine
      (3 mg kg-1 h-1). The mexiletine levels in blood plasma and parotid and mandibular
      saliva declined biexponentially with time in almost parallel fashion. Although
      the mexiletine levels in both types of saliva were lower than that in plasma, the
      drug level in parotid saliva was always higher than that in mandibular saliva.
      Significant correlations were observed when all data relating mexiletine
      concentration in plasma and saliva were included (P less than 0.001). The
      saliva/plasma drug concentration ratios (S/P ratios) did not vary to a large
      extent (0.56 +/- 0.10 for parotid saliva, 0.21 +/- 0.06 for mandibular saliva),
      but there was a consistent tendency for the higher plasma drug levels in the
      distribution phase to produce relatively high S/P ratios for both parotid and
      mandibular saliva. Moreover, the plasma mexiletine levels calculated by the
      equation of Matin et al (1974) employing the observed values for the saliva drug
      level, saliva pH and free fraction of mexiletine in plasma were significantly
      higher than the observed drug levels. Therefore, it is suggested that the
      salivary excretion of mexiletine could not be explained quantitatively by simple,
      passive secretion based on pH-partition theory.

PMID- 1350631
TI  - Comparative pharmacokinetics of tetrahydropyranyl-doxorubicin and doxorubicin in
      rat isolated lung.
AB  - Rat isolated perfused lungs (Sprague-Dawley rats, n = 20) were studied to compare
      the pulmonary uptake of a new anthracycline, tetrahydropyranyl-doxorubicin (THP
      DXR) with that of doxorubicin (DXR). Lung perfusions were initiated with a
      constituted medium containing either drug at concentrations of 1, 10 or 100
      microM. Lungs were perfused by recirculation for 60 min. Thirteen perfusate
      samples were collected over 60 min and subjected to HPLC for assay. The perfusate
      concentration of THP-DXR decreased to 24 +/- 5% of the initial concentration and
      to 8 +/- 2%, 20 and 60 min after the beginning of the infusion, respectively.
      Corresponding values for DXR were 77 +/- 16 and 52 +/- 15%, respectively (P less
      than 0.05). During the THP-DXR perfusion, the area under the perfusate
      concentration vs time curve (AUC) was decreased to one-third and the clearance
      was increased 3-fold (P less than 0.05). The pulmonary concentration of THP-DXR
      reached 0.032 +/- 0.01 mumol g-1 60 min after the beginning of a perfusion of 1
      microM of the drug. This concentration increased to 0.379 +/- 0.11 mumol g-1 when
      the initial dose concentration was 10 microM. Corresponding lung concentrations
      for DXR were 0.013 +/- 0.001 and 0.150 +/- 0.04 mumol g-1, respectively (P less
      than 0.05). The perfusate concentration/initial concentration ratio decreased by
      the same amount whether a 1 or 10 microM initial concentration of either drug was
      used. An initial concentration of 100 microM of THP-DXR, unlike DXR, consistently
      induced oedema in the perfused lung. No metabolite of either drug was revealed
      during the course of our study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350632
TI  - Potassium markedly potentiates the effect of veratridine on dopamine release from
      rat superfused striatal ribbons.
AB  - The effects of veratridine-induced depolarization on [3H]dopamine ([3H]DA)
      release in the presence of a physiological (5 mM) or a depolarizing (25 mM)
      concentration of K+ were studied in-vitro in rat superfused striatal ribbons. A
      combination of the two depolarizing agents induced a marked potentiation in the
      overflow of [3H]DA, giving an overall 3- to 5-fold increase in veratridine
      activity. This potentiation was completely antagonized by tetrodotoxin (100 nM).
      These studies indicated that K(+)-induced depolarization can increase the potency
      of veratridine in releasing dopamine from terminals.

PMID- 1350633
TI  - Torasemide, but not frusemide, increases intracellular cAMP and cGMP content in
      the aorta of the renal hypertensive rat.
AB  - Repeated oral administration of the novel loop diuretic torasemide (3 mg kg-1)
      and frusemide (30 mg kg-1) for 7 days, elicited a significant fall in the
      systolic blood pressure in the one-kidney, one-clip Goldblatt renal hypertensive
      rat (RHR). The hypotensive action was greater in the torasemide group than in the
      frusemide group. Furthermore torasemide increased intracellular cAMP and cGMP
      content in aorta of RHR. Frusemide caused no effect. It is hypothesized that the
      increase in adenosine- or guanosine-nucleotides is involved in the
      antihypertensive action of torasemide, but not in that of frusemide.

PMID- 1350635
TI  - Partition and distribution coefficients of aryloxypropanolamine beta-adrenoceptor
      antagonists.
AB  - n-Octanol/water partition and distribution coefficients of fifteen beta-blockers
      have been measured and the relationships between log P (neutral species), log Pi
      (fully ionized species) and log D7.4 have been examined. A strict correlation
      exists among these three parameters, suggesting that the ionization exerts
      similar effects on the partition behaviour of these drugs.

PMID- 1350634
TI  - Similar central actions of intravenous methohexitone suspension and solution in
      the rabbit.
AB  - The central actions of solutions of methohexitone sodium and suspensions of
      methohexitone given intravenously in equimolar doses have been compared. The
      administrations induced identical anaesthesia. Because, in general, drugs acting
      upon the central nervous system are poorly soluble in water, this finding should
      be useful for routine pharmacological investigations as it avoids the use of
      organic solvents which may themselves affect the central nervous system.

PMID- 1350636
TI  - Comparison of nebuliser efficiency for aerosolizing pentamidine.
AB  - Inhaled pentamidine has become an important method of treatment and prophylaxis
      for Pneumocystis carinii pneumonia and we have compared nebuliser efficiency in
      terms of drug output and droplet sizes in four brands of jet nebuliser (Acorn-22,
      Inspiron, Cirrus, Respirgard II) and one brand of ultrasonic nebuliser (Fisoneb),
      at 2 pentamidine concentrations and 3 flow rates, using a laser particle sizer.
      Droplet size (which varied from 1.2 to 4.7 microns mass median diameter) was
      dependent in all cases, except with the Respirgard II system, on the flow rate of
      the gas driving the equipment and the concentration of pentamidine used. Drug
      output varied significantly between nebuliser brands and for a 300 mg dose of
      pentamidine was: 61% for the Acorn-22, 62% for the Inspiron, 49% for the Fisoneb
      and 43% for the Respirgard II. Both droplet size and drug output are important in
      determining nebuliser efficiency.

PMID- 1350637
TI  - Voltage- and time-dependent inhibition of neuronal calcium channels by a GTP
      binding protein in a mammalian cell line.
AB  - 1. Inhibitory modualtion of the three Ca2+ channel current components by
      neurotransmitters was studied using the whole-cell patch-clamp method in a
      mammalian cell line, NG108-15. 2. In cells differentiated with dibutyryl cyclic
      AMP, both the low-voltage-activated current (ILVA) and omega CgTX-sensitive high
      voltage-activated current (I omega CgTX) could be inhibited by [D-phen2, D
      phen5]enkephalin, acetylcholine and noradrenaline. In contrast, differentiation
      with prostaglandin E1 and theophylline eliminated the agonist-induced inhibition
      of ILVA, but enhanced that of I omega CgTX. The DHP-sensitive high-voltage
      activated current was unaffected by the transmitters in most of the cells. 3. The
      inhibition was prevented by pre-treatment of cells with pertussis toxin,
      suggesting involvement of a G-protein. Long treatment of the cells with phorbol
      ester did not prevent the inhibition. 4. The inhibition was always partial: the
      maximal inhibition was 40% for ILVA and 70% for I omega CgTX. 5. The inhibition
      of ILVA and I omega CgTX was relieved during depolarization. Half-maximal relief
      of inhibition of I omega CgTX was attained at 0 mV, irrespective of agonist
      concentration. 6. The kinetics of removal and re-establishment of inhibition were
      voltage dependent. Both processes were single exponentials and had identical time
      constants at a given membrane potential. Time constants were 124 ms at -40 mV,
      160 ms at 0 mV and 8 ms at 60 mV, at any agonist concentration. 7. Time courses
      of tail currents were unaltered by the inhibition. 8. The inhibition of the omega
      CgTX-sensitive Ca2+ channel can be described as a shift in gating modes; with an
      additional voltage-dependent gating state activated by the agonists. The voltage
      dependent properties of this modulation allow inhibition of Ca2+ channel to be
      overcome by high-frequency trains of action potentials.

PMID- 1350639
TI  - Monitoring neuroleptics.

PMID- 1350638
TI  - Regulation of single quantal efficacy at the snake neuromuscular junction.
AB  - 1. Postsynaptic responses to spontaneous quantal transmitter release have been
      compared among neuromuscular junctions in a thin snake muscle. For each junction
      the type, diameter, and input conductance, G(in) of the postsynaptic muscle fibre
      were determined. Particularly among fibres of a given type, G(in) was directly
      correlated with fibre diameter. 2. Miniature endplate potentials (MEPPs) were
      recorded intracellularly near endplates visualized with Nomarski optics. Mean
      MEPP amplitude decreased with increasing G(in) among fibres in one muscle.
      However, the dependence of mean amplitude upon G(in) was not ohmic, as would be
      expected if the underlying single quantal currents (miniature endplate currents,
      MEPCs) were of similar amplitude at all junctions. Instead, the relation between
      MEPPs and G(in) suggested that mean MEPC amplitudes, calculated as mean MEPP
      amplitude x G(in), increased with increasing G(in). 3. MEPCs were recorded
      directly using the two-microelectrode voltage clamp technique. Mean MEPC
      amplitudes depended systematically on G(in), again such that MEPCs were on
      average larger in fibres with higher G(in). 4. MEPCs were recorded
      extracellularly from small regions of endplates (underlying a few nerve terminal
      boutons). Amplitudes of MEPCs depended on G(in) or fibre diameter in the same
      manner as amplitudes of MEPCs recorded by intracellular voltage clamp. 5. When
      the anticholinesterase agent neostigmine was added to the bath, amplitude and
      duration of MEPPs, MEPCs, and extracellular MEPCs increased. However, the
      systematic dependence of mean MEPC amplitude on G(in) or fibre diameter remained.
      6. Evoked subthreshold endplate potentials (EPPs) were recorded under conditions
      of low extracellular Ca2+. Endplate currents (EPP amplitudes x G(in)) were
      systematically larger in fibres with larger G(in), indicating regulation of
      evoked synaptic current in the muscle. The regulation was found to be due to a
      combination of increased quantal content and larger single quantal currents in
      larger (higher G(in)) fibres. 7. Synaptic size, assessed either by area of
      cholinesterase staining or number of terminal boutons, increased with increasing
      fibre diameter. Assuming that quantal content is proportional to synaptic size,
      this relation was sufficient to account for the observed increase in quantal
      content with increasing G(in) among fibres in the muscle, but was not alone
      sufficient to account for the observed regulation of evoked current. 8. It is
      concluded that the efficacy of individual transmitter quanta released at the
      snake neuromuscular junction is regulated such that large muscle fibres receive
      larger single quantal currents. Regulation of single quantal current contributes
      substantially to overall regulation of synaptic strength in the muscle.

PMID- 1350641
TI  - Pediatric Rheumatology into the 90s. Proceedings. Park City, Utah, March 2-6,
      1991.

PMID- 1350640
TI  - Sulfasalazine induced agranulocytosis treated with granulocyte-macrophage colony
      stimulating factor.
AB  - We report the use of granulocyte-macrophage colony stimulating factor (GM-CSF) in
      a case of rheumatoid arthritis with sulfasalazine induced agranulocytosis,
      leading to a rapid bone marrow recovery within 7 days. This case and 2 others
      reported in the literature emphasize the need for further research into the
      possible role of GM-CSF in the treatment of drug induced agranulocytosis.

PMID- 1350642
TI  - RNase T1 mutant Glu46Gln binds the inhibitors 2'GMP and 2'AMP at the 3' subsite.
AB  - On the basis of molecular dynamics and free-energy perturbation approaches, the
      Glu46Gln (E46Q) mutation in the guanine-specific ribonuclease T1 (RNase T1) was
      predicted to render the enzyme specific for adenine. The E46Q mutant was
      genetically engineered and characterized biochemically and crystallographically
      by investigating the structures of its two complexes with 2'AMP and 2'GMP. The
      ribonuclease E46Q mutant is nearly inactive towards dinucleoside phosphate
      substrates but shows 17% residual activity towards RNA. It binds 2'AMP and 2'GMP
      equally well with dissociation constants of 49 microM and 37 microM, in contrast
      to the wild-type enzyme, which strongly discriminates between these two
      nucleotides, yielding dissociation constants of 36 microM and 0.6 microM. These
      data suggest that the E46Q mutant binds the nucleotides not to the specific
      recognition site but to the subsite at His92. This was confirmed by the crystal
      structures, which also showed that the Gln46 amide is hydrogen bonded to the
      Phe100 N and O atoms, and tightly anchored in this position. This interaction may
      either have locked the guanine recognition site so that 2'AMP and 2'GMP are
      unable to insert, or the contribution to guanine recognition of Glu46 is so
      important that the E46Q mutant is unable to function in recognition of either
      guanine and adenine.

PMID- 1350643
TI  - Small subgroup of aggressive, highly proliferative prostatic carcinomas defined
      by p53 accumulation.
AB  - BACKGROUND: Mutations in the p53 gene resulting in the accumulation of altered
      p53 proteins with prolonged half-life have been found in a large variety of human
      malignancies. PURPOSE: We studied the significance of p53 protein accumulation in
      prostatic carcinoma. METHODS: The material consisted of 137 paraffin-embedded,
      primary prostatic carcinomas. Accumulation of p53 protein was studied by
      immunohistochemical staining using a polyclonal p53-specific CM-1 antibody.
      Proliferation activity was determined by DNA flow cytometry and by
      immunohistochemical detection of proliferative cell nuclear antigen (PCNA) using
      a monoclonal PC10 antibody. RESULTS: Eight (6%) of the tumors showed intense p53
      staining in more than 20% of the tumor cells, 15 (11%) had only lower level
      immunoreactivity, and 114 (83%) showed no staining. High-level p53 accumulation
      was associated with high histologic grade (P less than .001), DNA aneuploidy (P
      less than .05), and high cell proliferation rate as defined by flow cytometric S
      phase analysis (P less than .01) or PCNA expression (P less than .01). High-level
      p53 accumulation predicted short, progression-free interval (P less than .01) and
      poor survival (P less than .001), with about a 12-fold relative risk of death as
      compared with p53-negative cases. Low-level p53 accumulation had no prognostic
      significance. CONCLUSIONS: Accumulation of p53 confers proliferative advantage
      for prostatic carcinoma cells and defines a small subgroup of highly malignant
      carcinomas.

PMID- 1350644
TI  - Reactivity to fucose-binding proteins of Lotus tetragonolobus correlates with
      metastatic phenotype of transitional cell carcinoma of the bladder.
AB  - Expression of binding sites for fucose binding proteins (FBP) of Lotus
      tetragonolobus were immunohistochemically analyzed in surgically extirpated
      specimens from patients with transitional cell carcinoma of the bladder. The
      degree of expression of FBP binding sites in the primary cancerous region
      correlated with the occurrence of lymph node metastasis. Thus, lymph node
      metastases occurred in 15 of 34 cases with high expression of FBP binding sites,
      but did not in 17 cases with low or no FBP binding site expression. All
      metastatic lymph nodes strongly reacted with FBP. In addition, primary lesions at
      the pT3b or pT4 stage more frequently reacted with FBP as compared with those at
      the pTa, pT1 or pT2 stage. Although FBP is known to react both with Gal beta 1---
      4(Fuc alpha 1----3)GlcNAc and Fuc alpha 1----2Gal sequences, comparative staining
      of other carbohydrate markers revealed that the latter structure is not related
      with metastatic potential and stages.

PMID- 1350645
TI  - Modulation of noradrenergic transmission by neuropeptide Y and presynaptic alpha
      2-adrenergic receptors in the hypothalamus of spontaneously hypertensive rats.
AB  - Neuropeptide Y (NPY) has a wide and specific distribution in the central nervous
      system, and is colocalized with catecholamines in specific neuronal systems. In
      this study, in order to investigate the regulatory mechanisms of NPY and
      presynaptic alpha 2-adrenergic receptors on central noradrenergic transmission in
      hypertension, we have examined the effects of NPY and the alpha 2-agonist, UK
      14,304, on (3H)-noradrenaline (NA) release from hypothalamic slices of
      spontaneously hypertensive rats (SHR). Electrical stimulation (1 Hz)-evoked (3H)
      NA release was significantly greater in the hypothalamic slices of SHR than in
      those of Wistar Kyoto rats (WKY). NPY and the alpha 2-agonist, UK 14,304,
      inhibited the stimulation-evoked (3H)-NA release in a dose-related manner. The
      inhibitory effects of NPY and UK 14,304 on NA release were significantly
      attenuated in SHR compared with WKY. These results suggest that NPY and alpha 2
      adrenoceptors might be involved in the regulation of central sympathetic nervous
      activity in hypertension.

PMID- 1350646
TI  - [Expression of c-erbB-2 protein in gastric carcinomas--correlation between
      immunohistochemical study and clinico-pathological factors, DNA ploidy pattern
      and concentration of c-erbB-2 protein in serum].
AB  - Expression of c-erbB-2 protein in carcinoma tissue was examined in 56 patients
      suffered from gastric carcinoma, and the correlation between the expression of c
      erbB-2 protein and clinico-pathological factors, DNA ploidy pattern was also
      examined. Positive expression of c-erbB-2 protein in carcinoma tissue was
      detected in 21/56 (37.5%) cases, and the positive rate (71.4%) in tissue of
      differentiated carcinoma (pap, tub1, tub2) was significantly higher than that in
      tissue of undifferentiated carcinoma (por, sig, muc) (28.6%). No good correlation
      between the expression of c-erbB-2 in tissue and other clinico-pathological
      factors, such as ly, v, n, tumor size, stage of the tumor, and the location of
      the tumor was observed. In DNA ploidy, 70.6% of cases was aneuploid pattern, and
      29.4% of cases was diploid pattern in positive expression of c-erbB-2 protein in
      carcinoma tissue. These results suggest that expression of c-erbB-2 protein is
      involved in promoting DNA synthesis in initial step of differentiated gastric
      carcinoma. The concentration of c-erbB-2 in serum of positive expression of c
      erbB-2 protein in tissue was significantly higher than that in serum of negative
      expression of c-erbB-2 protein in tissue. Good correlation between serum
      concentration of c-erbB-2 protein and clinical stage of the carcinoma was
      observed in positive expression of c-erbB-2 protein in carcinoma tissue. The
      concentration of c-erbB-2 protein in serum can be a sensitive indicator for guess
      the Stage of the gastric carcinoma that express c-erbB-2 protein in carcinoma
      tissue.

PMID- 1350647
TI  - [A case of pancreatic fistula cured spontaneous internal fistulization].

PMID- 1350648
TI  - Analysis of HLA class II genes in Japanese patients with idiopathic membranous
      glomerulonephritis.
AB  - Thirty unrelated Japanese adult patients with idiopathic membranous
      glomerulonephritis (IMG) and 50 unrelated Japanese normal controls were examined
      for HLA class II genes. Both the 3.0 kb DQB and the 6.2 kb DQA restriction
      fragments were simultaneously identified in 86.7% of the patients. These were
      significantly different from the 14% frequency of the fragments in controls
      (relative risk = 39.9; P = 1.7 x 10(-10)). The haplotype DR2-DQwl associated with
      IMG seemed to be Dw2 which was essentially different from the haplotype common to
      the normal Japanese population. Dw12. This was because most of the restriction
      fragment length polymorphism (RFLP) of DQB and DQA of the patients coincided with
      that of homozygous cell lines with Dw2. The DRB probe showed no significant
      differences in the hybridization patterns between the patient group and HLA
      matched controls. These findings indicate that the specific HLA-DQ polymorphism
      correlates primarily with Japanese IMG.

PMID- 1350649
TI  - Inhibition of leukocyte-endothelial adherence following thermal injury.
AB  - Progressive microvascular damage in the tissue adjacent to a cutaneous burn
      injury results in extension of burn size. The role of neutrophils (PMNs) in the
      pathogenesis of microvascular injury was investigated by inhibition of PMN
      adherence to the microvascular endothelium using monoclonal antibodies directed
      to the leukocyte CD18 adhesion complex or its endothelial ligand, intercellular
      adhesion molecule-1 (ICAM-1, CD54). A model of thermal injury was developed using
      New Zealand White rabbits. Under general anesthesia two sets of three full
      thickness burns separated by two 5 x 30-mm zones were produced by applying brass
      probes heated to 100 degrees C to the animals' backs for 30 sec. Cutaneous blood
      flow determinations were obtained for 72 hr. Blood flow measurements were
      performed using a laser doppler blood flowmeter (PF3, Perimed, Piscataway, NJ).
      There were five experimental groups; controls given saline alone, n = 12; animals
      given monoclonal antibody to the PMN CD18 complex, R 15.7 prior to burn injury
      (pre-R15.7, n = 5); animals given R 15.7 30 min after burn injury (post-R 15.7, n
      = 6); animals given the anti ICAM-1 antibody, R 6.5 prior to burn (pre-R 6.5, n =
      6); and animals given the R 6.5 30 min postburn injury (post-R 6.5, n = 6). BF in
      the marginal "zone of stasis" between burn contact sites was significantly higher
      in the antibody-treated animals and administration of the antibodies 30 min after
      injury was as effective as preburn administration in preserving blood
      flow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350650
TI  - Insulin-like growth factors I and II expression in the healing wound.
AB  - Demonstrating temporal variation in the expression of messenger RNA (mRNA) for
      growth factors may give some indication as to whether growth factor synthesis is
      regulated in wound healing. The aim of this study was to evaluate the expression
      of insulin-like growth factors (IGF) I and II in the wound. Two wound models, an
      incisional model and a subcutaneous sponge implant model, were used in this
      study. The RNA was extracted and reverse transcribed and mRNA was amplified using
      polymerase chain reaction (PCR). Semiquantitation of PCR products was
      accomplished using [3H]dGTP incorporation. Levels of expression for both IGF-I
      and -II were found to be low in unwounded skin and at 12 hr postwounding.
      However, in both wound models expression increased substantially from 1 to 21
      days postwounding. Both factors also were found to be expressed by fibroblasts
      and polymorphonuclear leukocytes (PMN). Additionally, two transcripts were found
      for IGF-II, the larger of which appeared to be specific for PMN and possibly
      cells involved in angiogenesis. Levels of message expressed in healing wounds for
      IGF-I and -II appear to be regulated with the highest levels of message found at
      time points coinciding with fibroblast predominance in the wound. Since
      fibroblasts are known to both secrete and respond to IGF-I, it is possible that
      IGF-I and IGF-II are acting to influence fibroblast differentiation and function
      in the later stages of wound healing.

PMID- 1350651
TI  - Demonstration of clonality, by X-linked DNA analysis, in chronic natural killer
      cell lymphocytosis and successful therapy with oral cyclophosphamide.
AB  - The expanded lymphocyte population in large granular lymphocyte (LGL)-leukemia
      carries the phenotypic characteristics of either cytotoxic T lymphocytes
      (CD3+,CD8+) or natural killer (NK) cells (CD3-,CD15+). In the former subset,
      clonality has been demonstrated by T-cell receptor gene rearrangement studies.
      Since NK cells do not rearrange T-cell receptor genes, the neoplastic nature of
      chronic NK cell lymphocytosis has not been well defined. We used X-linked DNA
      analysis to study the clonal nature of an expanded NK cell population in a
      patient with a 3-year history of relative lymphocytosis associated with anemia
      and neutropenia. Southern blot analysis showed no clonal T-cell receptor gene
      rearrangement. The majority of the circulating lymphocytes had a NK cell
      phenotype and demonstrated both direct NK cell-mediated cytotoxicity and antibody
      dependent cellular cytotoxicity. However, the in vitro growth characteristics of
      these cells did not suggest that they were polyclonal expansions of normal NK
      cells. To determine directly the clonal origin of these cells, we performed X
      linked DNA analysis. Density gradient centrifugation methods were used to isolate
      mononuclear cells, and NK cells were positively selected by CD16-immunoconjugated
      magnetic beads. The DNA of these cells was analyzed by restriction fragment
      length polymorphism-methylation strategy and showed a monoclonal pattern of X
      chromosome inactivation while a polyclonal pattern was obtained in corresponding
      skin tissue. Treatment of the patient with oral cyclophosphamide resulted in
      complete hematologic remission. We conclude that chronic NK lymphocytosis may be
      clonal and responsive to immunosuppressive therapy.

PMID- 1350652
TI  - Effect of position 185 mutations of the MDR-1 gene on drug resistance in
      leukaemia.

PMID- 1350653
TI  - Effects of reserpine on tyrosine hydroxylase mRNA levels in locus coeruleus and
      medullary A1 and A2 neurons analyzed by in situ hybridization histochemistry and
      quantitative image analysis methods.
AB  - These studies examined the effects of reserpine on concentrations of
      norepinephrine (NE), dopamine (DA) and epinephrine (EPI) and on levels of
      tyrosine hydroxylase (TH) mRNA in locus coeruleus (LC) and medullary A1 and A2
      neurons. Noradrenergic neurons in these regions first were identified by
      immunocytochemistry and, thereafter, by in situ hybridization histochemistry.
      Levels of TH mRNA were measured by quantitative image analysis methods. Changes
      in catecholamine concentrations in micropunches of these brain regions were
      analyzed by HPLC. Epinephrine was not detected in any of the nuclei examined.
      Twenty-four hours after reserpine treatment, NE concentrations declined in A1, A2
      and LC neurons by 46, 69 and 34% respectively while DA declined only in the
      region of A2 neurons. This reserpine-induced depletion of NE was accompanied by a
      2- to 3-fold increase in TH mRNA levels in LC and A1 neurons but no change in
      message levels occurred in A2 cells 24 h after reserpine. Forty eight hours
      later, message levels in A1 and LC neurons did not differ significantly from the
      elevated 24 h values but TH mRNA levels in A2 neurons now were significantly
      elevated compared to 24 h values. TH mRNA levels 72 h after reserpine did not
      differ from 48 h values in A1, A2 and LC neurons. Thus, TH gene expression in A1
      neurons increases after reserpine treatment in a manner equivalent to that
      observed in LC, adrenal medulla and superior cervical ganglia. The reason why it
      required 48 h for TH mRNA to increase in A2 neurons remains unclear.

PMID- 1350654
TI  - Changes in tyrosine hydroxylase mRNA levels in medullary A1 and A2 neurons and
      locus coeruleus following castration and estrogen replacement in rats.
AB  - Temporal changes in tyrosine hydroxylase (TH) mRNA levels in medullary A1 and A2
      neurons and locus coeruleus (LC) cells were studied 6, 12 and 24 h following
      orchidectomy in rats. Brains from intact controls and sham castrated rats also
      were evaluated at these same time periods. In situ hybridization histochemistry
      and quantitative image analysis techniques were used to quantitate levels of
      cytoplasmic TH mRNA. Neither the time of day nor the stress of sham castration
      affected TH mRNA levels in A1, A2 and LC neurons. In contrast, 6 h following
      castration, TH mRNA levels in A1 neurons had declined significantly. Thereafter,
      there was a linear increase in A1 message levels such that, by 24 h, TH mRNA
      values were significantly higher than those obtained in intact controls.
      Placement of Silastic estrogen capsules immediately after castration prevented
      the 6 h decline in A1 message levels. At 12 h, TH mRNA levels in A1 neurons were
      significantly higher in estrogen-treated rats compared to those of the castrate
      or intact control groups. By 24 h, message levels in A1 neurons of steroid
      treated rats were comparable to the intact control. Neither castration nor
      estrogen treatment altered TH mRNA levels in A2 neurons. TH mRNA levels in LC
      neurons increased significantly 6 h after castration and estrogen produced a
      further significant increase in message levels. Six hours later (12 h), TH mRNA
      values were still higher than controls but, in the estrogen-treated group, these
      levels had declined to those observed in the 12 h castrate group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1350655
TI  - 1H spectroscopic imaging of rat brain at 7 tesla.
AB  - 1H magnetic resonance spectroscopic imaging has been used to obtain metabolite
      maps of the rat brain. The spin-echo-based technique has been evaluated with
      respect to water and lipid suppression and sensitivity. Metabolite maps were
      constructed for choline, creatine + phosphocreatine, amino acids, N-acetyl
      aspartate, and lactate. A spatial resolution of 3 x 3 mm (in plane) with 7-mm
      thick slices was achieved routinely in 60-min (16 x 16 phase encodings)
      acquisitions. For higher intensity resonances, metabolite maps could be
      constructed in as little as 10 min. Results from phantoms and from rats under
      normal and focal ischemia conditions are presented.

PMID- 1350656
TI  - Localized 1H NMR spectra of glutamate in the human brain.
AB  - Localized 1H NMR spectra at TE = 12 ms were obtained from cerebral cortex of
      human subjects using ISIS with surface suppression. The 2.29-ppm resonance was
      assigned to C4 glutamate with contributions from C4 glutamine and GABA using in
      vivo spectral editing and comparison of chemical shift with pure compounds. The
      measured intensity ratio between the 2.29 resonance and the creatine resonance at
      3.03 ppm was in good agreement with the ratio predicted from previously reported
      measurements of glutamate, glutamine, and GABA concentrations in biopsied human
      brain tissue.

PMID- 1350657
TI  - Report on a conference on organic solvents and the nervous system.
AB  - At two scientific conferences in 1985, one in Copenhagen sponsored by the Nordic
      Council of Ministers and the World Health Organization (WHO), the other in
      Raleigh, NC, it was concluded that chronic toxic encephalopathy may develop
      following long-term occupational exposure to organic solvents (1,2). The terms
      organic affective syndrome, mild and severe chronic toxic encephalopathy were
      suggested for this condition describing increasing severity. In May 1990, a
      conference on organic solvents and the nervous system was held in Copenhagen
      sponsored by the Commission of the European Communities and the Danish Ministry
      of the Environment (3). Scientists and representatives from the governments,
      industries, and labour organisations from the EEC and US participated.

PMID- 1350658
TI  - Seroprevalence of HTLV-I and HTLV-II.

PMID- 1350659
TI  - Seroprevalence of HTLV-I and HTLV-II.

PMID- 1350660
TI  - Introns in sequence tags.

PMID- 1350661
TI  - Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV.
AB  - Coronaviruses, like many animal viruses, are characterized by a restricted host
      range and tissue tropism. Transmissible gastroenteritis virus (TGEV), a major
      pathogen causing a fatal diarrhoea in newborn pig, replicates selectively in the
      differentiated enterocytes covering the villi of the small intestine. To
      investigate the molecular determinants of the infection, we characterized the
      surface molecule used by the virus for binding and entry into host cells. Here we
      report that aminopeptidase N, an ectoenzyme abundantly expressed at the apical
      membrane of the enterocytes, serves as a receptor for TGEV. Monoclonal antibodies
      were selected for their ability to block infection by TGEV of porcine cell lines.
      They recognized a brush-border membrane protein of M(r) 150K, which was
      identified as aminopeptidase N by amino-terminal sequencing. Two lines of
      evidence supported the view that the peptidase itself acts as a receptor. First,
      virions bound specifically to aminopeptidase N that was purified to homogeneity.
      Second, recombinant expression of aminopeptidase N conferred infectivity by TGEV
      to an otherwise non-permissive cell line.

PMID- 1350662
TI  - Human aminopeptidase N is a receptor for human coronavirus 229E.
AB  - Human coronaviruses (HCV) in two serogroups represented by HCV-229E and HCV-OC43
      are an important cause of upper respiratory tract infections. Here we report that
      human aminopeptidase N, a cell-surface metalloprotease on intestinal, lung and
      kidney epithelial cells, is a receptor for human coronavirus strain HCV-229E, but
      not for HCV-OC43. A monoclonal antibody, RBS, blocked HCV-229E virus infection of
      human lung fibroblasts, immunoprecipitated aminopeptidase N and inhibited its
      enzymatic activity. HCV-229E-resistant murine fibroblasts became susceptible
      after transfection with complementary DNA encoding human aminopeptidase N. By
      contrast, infection of human cells with HCV-OC43 was not inhibited by antibody
      RBS and expression of aminopeptidase N did not enhance HCV-OC43 replication in
      mouse cells. A mutant aminopeptidase lacking the catalytic site of the enzyme did
      not bind HCV-229E or RBS and did not render murine cells susceptible to HCV-229E
      infection, suggesting that the virus-binding site may lie at or near the active
      site of the human aminopeptidase molecule.

PMID- 1350663
TI  - [National testes registration].

PMID- 1350664
TI  - The Third International Conference on Alzheimer's Disease and Related Disorders.
      July 12-17, 1992, Abano Terme, Italy. Abstracts.

PMID- 1350665
TI  - Pharmacological characterization of dopamine systems in the nucleus accumbens
      core and shell.
AB  - Recent anatomical data suggest that the nucleus accumbens can be parcellated into
      a core region, related to the caudate-putamen, and a shell region, associated
      with the limbic system. We have used pharmacological methods to characterize the
      dopamine innervations of the nucleus accumbens core and shell in the rat.
      Concentrations of both dopamine and serotonin were significantly greater in the
      nucleus accumbens shell than the nucleus accumbens core. Metabolite: amine ratios
      suggested that both dopamine and serotonin utilization are greater in the core.
      However, dopamine turnover (as determined by measuring the rate of decline of
      dopamine after alpha-methyl-p-tyrosine treatment) was not significantly different
      in the two accumbal sectors. Dopamine concentrations in the two nucleus accumbens
      sectors were decreased to an equivalent degree at both 4 and 18 h after reserpine
      administration. In contrast, serotonin concentrations were decreased to a
      significantly greater degree in the nucleus accumbens core than nucleus accumbens
      shell at 4 h, but not 18 h, after reserpine administration. Administration of
      haloperidol increased dopamine utilization in both nucleus accumbens sectors, but
      augmented utilization to a significantly greater degree in the nucleus accumbens
      core. Clozapine increased dopamine utilization to an equivalent degree in both
      nucleus accumbens regions. Short duration immobilization stress selectively
      increased dopamine utilization in the nucleus accumbens shell. These data
      indicate that there are significant differences between the nucleus accumbens
      core and nucleus accumbens shell in basal dopamine metabolism, and indicate that
      the core and shell dopamine innervations can be distinguished on the basis of
      response to both pharmacological and environmental challenges.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1350666
TI  - Pindolol antagonizes the effects on hippocampal rhythmical slow activity of
      clonidine, baclofen and 8-OH-DPAT, but not chlordiazepoxide and sodium
      amylobarbitone.
AB  - Buspirone, benzodiazepines, barbiturates and ethanol all reliably reduce the
      frequency of reticular-elicited hippocampal rhythmical slow activity. In the
      present experiments we tested a number of drugs which are not usually used for
      treating generalized anxiety disorders but which have been reported to have some
      anxiolytic properties. Clonidine (0.3 mg/kg, i.p.), baclofen (6 mg/kg, i.p.) and
      8-hydroxy-di-n-propylamino tetralin (8-OH-DPAT) (2.5 mg/kg, i.p.) all reduced the
      frequency of rhythmical slow activity. The effect of all three drugs was reduced
      by the 5-hydroxytryptamine 1a antagonist pindolol (2 mg/kg, i.p.). Pindolol had
      no effect on the reduction in rhythmical slow activity produced by sodium
      amylobarbitone, as has been previously reported for the benzodiazepine
      chlordiazepoxide. Flumazenil (10 mg/kg, i.p.), a benzodiazepine receptor
      antagonist, reduced the effects of chlordiazepoxide (5 mg/kg, i.p.), but not
      buspirone (10 mg/kg, i.p.). A combination of the selective beta 1 adrenergic
      receptor antagonist metoprolol (20 mg/kg, i.p.) and the beta 2 adrenergic
      receptor antagonist ICI 118,551 (4 mg/kg, i.p.) did not reduce the effects of
      either buspirone (10 mg/kg, i.p.) or diazepam (1 mg/kg, i.p.). These data show
      that there are at least two separate routes through which anxiolytic agents
      reduce the frequency of hippocampal rhythmical slow activity. Buspirone,
      clonidine, baclofen and 8-OH-DPAT act via a system dependent on 5
      hydroxytryptamine 1a receptor activation. Benzodiazepines act via activation of
      the benzodiazepine receptor and probably share with barbiturates action at the
      GABA-benzodiazepine-chloride ionophore complex but do not produce their effects,
      directly or indirectly, by 5-hydroxytryptamine 1a receptor activation.

PMID- 1350667
TI  - Baroreceptor reflex inhibition induced by the stimulation of serotonin3 receptors
      in the nucleus tractus solitarius of the rat.
AB  - Previous studies suggested that in the nucleus tractus solitarius, cardiovascular
      responses to serotonin may involve the simultaneous activation of more than one
      receptor subtype. In the present study, the cardiovascular effects of the local
      application of serotonin and different serotonin3 agonists and antagonists into
      the nucleus tractus solitarius were analysed in intact and unilaterally
      ganglionectomized rats. Unilateral injections of serotonin (5-15 nmol) produced a
      dose-dependent increase in blood pressure and partially antagonized the arterial
      baroreflex responses evoked by an i.v. injection of phenylephrine. Similar blood
      pressures response were obtained after unilateral microinjections of
      phenylbiguanide (5 nmol) and 2-methyl-serotonin (5 nmol), two serotonin3 receptor
      agonists. Bilateral microinjections of serotonin or phenylbiguanide produced more
      pronounced blood pressure effects and antagonized completely the baroreflex
      responses. Both blood pressure and baroreflex effects were antagonized by prior
      injections of specific serotonin3 antagonists such as zacopride (100 pmol) and
      ondansetron (100 pmol). Concomitant autoradiographic studies performed in intact
      and ganglionectomized rats, using [125I]iodozacopride, confirmed that serotonin3
      receptors in the nucleus tractus solitarius are mainly located on vagal afferent
      fibers. In addition, serotonin microinjections made in the nucleus tractus
      solitarius ipsilateral to the ganglionectomy revealed a significant reduction in
      cardiovascular responses compared to intact animals. These results suggest that
      in the nucleus tractus solitarius of the rat, serotonin is involved in the reflex
      regulation of blood pressure through the stimulation of serotonin3 receptors
      presumably located on vagal afferent fibers. Since bicuculline antagonized the
      serotonin-mediated pressor responses, a serotonin3-dependent activation of an
      inhibitory GABAergic system within the nucleus tractus solitarius might be
      involved in blood pressure regulatory mechanisms.

PMID- 1350668
TI  - Confirmation of X-linked inheritance and provisional mapping of the keratosis
      follicularis spinulosa decalvans gene on Xp in a large Dutch family.
AB  - In a large Dutch family with keratosis follicularis spinulosa decalvans (KFSD,
      MIM 308800), DNA linkage analysis was performed in order to locate the gene.
      Pedigree analysis and lod score calculation confirmed X-linked inheritance and
      revealed significant linkage to DNA markers on Xp. A maximum lod score of 5.70 at
      theta = 0.0 was obtained with DXS41 (p99.6). The KFSD gene is tentatively located
      on Xp21.2-p22.2.

PMID- 1350669
TI  - A review of the clinical pharmacokinetics of pilocarpine, moxisylyte
      (thymoxamine), and dapiprazole in the reversal of diagnostic pupillary dilation.
AB  - An alpha-adrenergic blocking drug, dapiprazole, is now marketed in eyedrop form.
      Dapiprazole is being promoted as an agent suitable for reversing the diagnostic
      mydriasis produced by tropicamide or tropicamide and phenylephrine. The mechanism
      of action of dapiprazole is thought to be the same as that of moxisylyte
      (thymoxamine). The human pharmacokinetics for these drugs are reviewed and
      compared to pilocarpine. Published data indicate that either dapiprazole (0.5%)
      or moxisylyte (0.5%) enhance recovery from the mydriasis produced by tropicamide,
      phenylephrine, or their combination. However, because the published studies
      differ substantially in the doses of these mydriatics or in the miotics actually
      used, it is not possible to make any firm recommendations on how many drops of
      these new miotics should be instilled.

PMID- 1350670
TI  - Identification and analysis of the ret proto-oncogene promoter region in
      neuroblastoma cell lines and medullary thyroid carcinomas from MEN2A patients.
AB  - The human ret proto-oncogene (proto-ret), encoding a receptor tyrosine kinase, is
      highly expressed in neuroblastomas, medullary thyroid carcinomas (MTCs) and
      pheochromocytomas, which are all tumors of cells originating from the neural
      crest. In studies on the transcription mechanism of proto-ret, we identified the
      transcription start site and the promoter region by chloramphenicol acetyl
      transferase (CAT) assay. A sequence upstream from the transcription start site (
      167 to +98 bp) showed definite promoter activity in both proto-ret mRNA-positive
      neuroblastoma NB39-nu cells and proto-ret mRNA-negative HeLa cells. The promoter
      sequence had a high GC content and contained four tandemly repeated GC boxes
      without a TATA box. Putative binding sequences for SP-1, AP-2 and epidermal
      growth factor receptor-specific transcription factor (ETF) and also the
      transcription-suppressing factor, GC factor (GCF), were found in the repeated GC
      box region. Southern blot analysis of DNAs of neuroblastoma cell lines and
      primary MTCs showed that the high proto-ret expression in these tumors is not
      caused by gross genetic changes in the promoter region, suggesting the possible
      involvement of a region(s) other than the sequence from -167 to +98 bp or a minor
      genetic change(s) in the promoter region.

PMID- 1350671
TI  - Intragenic homozygous deletion of the WT1 gene in Wilms' tumor.
AB  - One example of intragenic homozygous deletion of the WT1 gene on chromosome 11p13
      was found after screening 42 samples of Wilms' tumor DNA from Japanese patients.
      After construction of a restriction map for the genomic sequence covering the 3'
      half of the gene, the deletion was analysed at the nucleotide sequence level. The
      deletion occurred in the patient's germline on his paternal chromosome, and most
      of the short arm of his maternal chromosome 11 was subsequently lost in the
      tumor. The size of the deletion was about 8 kb, removing exons 6 and 7 and
      resulting in premature termination. The deletion seemed to be created by
      recombination between short homologous sequences found in an Alu repeat, with a
      16-bp duplication left at the junction. This case conforms to a two-hit model for
      the genesis of a certain group of tumors, and supports the hypothesis that WT1 is
      one of the recessive oncogenes responsible for Wilms' tumor.

PMID- 1350672
TI  - Detection of a carrier state in Theileria parva-infected cattle by the polymerase
      chain reaction.
AB  - Two sets of oligonucleotide primers, one derived from a repetitive sequence and
      the other from the gene encoding a 67 kDa sporozoite antigen of Theileria parva,
      were used to amplify parasite DNA from the blood of T. parva-infected carrier
      cattle using the polymerase chain reaction (PCR). PCR amplification products were
      obtained from 15 carrier cattle infected with one of 4 different T. parva stocks.
      Successful amplifications were performed using DNA from 2 cattle infected with T.
      p. parva Pemba Mnarani, 10 cattle infected with T. p. parva Marikebuni, 2 cattle
      infected with T. p. bovis Boleni and 1 animal infected with T. p. lawrencei 7014.
      No amplification products were obtained from any of 7 cattle which had been
      infected with the T. p. parva Muguga stock. A synthetic oligonucleotide, which
      hybridized specifically to T. p. parva Marikebuni DNA among 6 T. parva stocks
      tested, was designed using sequence data from within the region of the T. parva
      genome amplified by the repetitive sequence primers. The oligonucleotide was used
      to probe PCR products and to increase the sensitivity and specificity of carrier
      animal detection. Southern blot analysis using a T. parva repetitive sequence
      probe demonstrated the existence of restriction fragment length polymorphisms
      between parasites isolated from T. p. parva Marikebuni-infected carrier cattle.
      The use of the PCR and other methods of carrier animal detection are discussed.

PMID- 1350674
TI  - Nordtox-92. 2nd Nordic Toxicology Congress. Humans in the toxic environment.
      Mariehamn, Aland Islands, Finland, May 6-10, 1992.

PMID- 1350673
TI  - Renal effects of alpha-adrenoceptor blockade during furosemide diuresis in
      conscious rats.
AB  - Clearance experiments were performed in conscious rats in order to investigate
      whether intravenous infusion of the non-selective alpha-adrenoceptor antagonist
      phentolamine could block compensatory sodium reabsorption during furosemide
      induced volume contraction. By measuring inulin clearance, urinary excretion
      rates of sodium and water, and lithium clearance, the effects on proximal and
      distal nephron segments were dissociated. The renal effect of intravenous
      infusion of 0.3 mg/kg/hr phentolamine (n = 6) was compared with time control
      animals (n = 9). Furosemide was administered as constant intravenous infusion
      (7.5 mg/kg/hr) with simultaneous phentolamine infusion at four dose levels: 0 (n
      = 9), 0.3 (n = 6), 1.0 (n = 7) and 3.0 mg/kg/hr (n = 6). Phentolamine infusion
      reduced norepinephrine-induced increase in blood pressure at all three dose
      levels (n = 5). Phentolamine infusion induced transient antidiuresis and a
      prolonged antinatriuretic response. Compared with rats given furosemide only,
      phentolamine attenuated dose-dependently the diuretic and natriuretic peak
      response to furosemide. This effect was associated with dose-dependent reductions
      in mean arterial pressure. The reduced natriuretic response was due to a reduced
      fractional sodium excretion in the distal nephron segment (at all doses of
      phentolamine) and a reduction of the glomerular filtration rate (1.0 and 3.0
      mg/kg/hr phentolamine). The fractional lithium excretion (FELi) increased to 65
      +/- 3% at 0.3 mg/kg/hr phentolamine during the natriuretic peak response of
      furosemide, while it only increased to 52 +/- 3% during furosemide alone. At
      steady-state conditions (120-180 min. after start of furosemide infusion) after
      infusion with furosemide plus 0.3 mg/kg/hr phentolamine the animals were still
      volume-depleted, but the compensatory tubular Na reabsorption in the proximal
      tubules was inhibited (FELi = 48 +/- 2% versus 39 +/- 1% in rats given furosemide
      alone). During furosemide infusion plasma epinephrine increased 700% and plasma
      norepinephrine increased 50%. These results are compatible with increased
      systemic sympathetic nervous activity and a contributory role of proximal tubular
      alpha-adrenoceptors in mediating compensatory sodium reabsorption during acute
      furosemide-induced volume contraction.

PMID- 1350675
TI  - Kinetic identification of a hydrogen bonding pair in the glucoamylase-maltose
      transition state complex.
AB  - Molecular recognition and site-directed mutagenesis are used in combination to
      identify kinetically, transition state interactions between glucoamylase (GA) and
      the substrate maltose. Earlier studies of mutant Glu180----Gln GA had indicated a
      role in substrate binding for Glu180 (Sierks, M.R., Ford, C., Reilly, P.J. and
      Svensson, B. (1990) Protein Engng, 3, 193-198). Here, changes in activation
      energies calculated from measured kcat/Km values for a series of deoxygenated
      maltose analogues indicate hydrogen bonding between the mutant enzyme and the 3
      OH group of the reducing end sugar ring. Using the same substrate analogues and
      determining activation energies with wild-type GA an additional hydrogen bond
      with the 2-OH group of maltose is attributed to an interaction with the
      carboxylate Glu180. This novel combination of molecular recognition and site
      directed mutagenesis enables an enzyme substrate transition state contact to be
      identified and characterized even without access to the three dimensional
      structure of the enzyme. Given the distant structural relationships between
      glucoamylases and several starch hydrolases (Svensson,B. (1988) FEBS Lett., 230,
      72-76), such identified contacts may ultimately guide tailoring of the activity
      of these related enzymes.

PMID- 1350676
TI  - The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced,
      double-stranded RNA-dependent protein kinase.
AB  - A vaccinia virus-encoded double-stranded RNA-binding protein, p25, has been
      previously implicated in inhibition of the interferon-induced, double-stranded
      RNA-activated protein kinase. In this study, we have identified the vaccinia
      viral gene (WR strain) that encodes p25. Amino acid sequence analysis of a
      chymotryptic fragment of p25 revealed a close match to the vaccinia virus
      (Copenhagen strain) E3L gene. The WR strain E3L gene was cloned and expressed
      either in COS-1 cells or in rabbit reticulocyte lysates in vitro. A M(r) 25,000
      polypeptide that could bind to poly(rI).poly(rC)-agarose and that reacted with
      p25-specific antiserum was produced in each case. In addition, COS cells
      expressing E3L gene products inhibited activation of the double-stranded RNA
      activated protein kinase in extracts from interferon-treated cells. Removal of
      E3L-encoded products by adsorption with anti-p25 antiserum resulted in loss of
      kinase inhibitory activity. These results demonstrate that the vaccinia virus E3L
      gene encodes p25 and that the products of the E3L gene have kinase inhibitory
      activity. Comparison of the deduced amino acid sequence of the E3L gene products
      with the protein sequence data base revealed a region closely related to the
      human interferon-induced, double-stranded RNA-activated protein kinase.

PMID- 1350677
TI  - Asymmetric distribution of oncogene products at mitosis.
AB  - Computer-assisted image analysis was used to demonstrate in exponentially
      proliferating human tumor cells the uneven postmitotic apportionment of several
      oncogene-encoded proteins (ras p21; erbB-2 p185; fos p55; myc p62). This
      observation may provide the explanation for the high degree of heterogeneity of
      postmitotic cells and the asynchrony in cell cycle traverse of cultured cells.

PMID- 1350679
TI  - Phosphorylation of nitrogen regulator I of Escherichia coli induces strong
      cooperative binding to DNA essential for activation of transcription.
AB  - We studied the effect of phosphorylation of nitrogen regulator I (NRI) on its
      binding properties. Both phosphorylated and unphosphorylated NRI bind linearly to
      a single binding site but cooperatively to two adjacent binding sites.
      Cooperative binding of NRI is severely affected by phosphorylation: half-maximal
      binding of NRI-phosphate is at 20-fold lower concentrations than that of
      unphosphorylated NRI. This is more due to a huge increase in the cooperativity
      constant--which is the strength of interaction between two NRI dimers--than to an
      increase in the microscopic binding constant which is the binding affinity to a
      single binding site. In vitro transcription and DNA footprinting experiments
      showed that occupation of a single binding site by NRI is not enough for
      efficient activation and that activation only occurs at a higher NRI
      concentration. We propose an activation mechanism for NRI in which the
      phosphorylation of NRI induces a conformational change in the N-terminal domains
      of the NRI-phosphate dimers, which now interact strongly with each other, leading
      to a tetramerization of NRI upon binding to two adjacent binding sites. We
      propose that not the phosphorylation of NRI itself but rather the tetramerization
      of NRI-phosphate on DNA binding induces the conformational change of the central
      domain to the active conformation.

PMID- 1350678
TI  - Homozygous hereditary C3 deficiency due to a partial gene deletion.
AB  - The molecular mechanism of C3 deficiency in an Afrikaans patient with recurrent
      pyogenic infections was studied. Restriction enzyme analysis showed a gene
      deletion of 800 base pairs (bp) mapping to the alpha chain of C3. Amplification
      of genomic DNA, using the PCR, demonstrated that the deletion included exons 22
      and 23 of the C3 gene. Truncated mRNA was shown in an Epstein-Barr virus
      transformed B-cell line by PCR amplification of first-strand cDNA. A consequence
      of this deletion was that the RNA transcribed 3' to the deletion was out of
      frame, resulting in formation of a stop codon 19 bp downstream from the deletion.
      The molecular basis of the deletion was compatible with homologous recombination
      between two Alu sequences located in introns 21 and 23. An unrelated
      nonconsanguineous relative and two of a sample of 174 Afrikaans-speaking
      individuals were heterozygous carriers of the same gene deletion. The wide
      prevalence of this null allele in this population is probably due to the effects
      of a small founder population. The presence of this deletion in the C3 gene is
      not compatible with production of any functional C3, supporting the idea that
      study of such patients offers a valid model for understanding physiological
      activities of C3 in vivo in humans.

PMID- 1350680
TI  - The gene for an inherited form of deafness maps to chromosome 5q31.
AB  - Primary--i.e., nonsyndromal-postlingual deafness is inherited as an autosomal
      dominant phenotype in a large kindred in Costa Rica. Genetically susceptible
      individuals begin to lose hearing at low frequencies at about age 10 years, after
      language and speaking are learned. Deafness inevitably progresses by age 30 years
      to bilateral hearing loss of all frequencies. Intelligence, fertility, and life
      expectancy are normal. The family traces its ancestry to an affected founder born
      in Costa Rica in 1754. We have mapped the gene for deafness in this kindred to
      chromosome 5q31, between the markers IL9 and GRL, by linkage analysis involving
      99 informative relatives.

PMID- 1350681
TI  - Effects of the dopamine D2 agonists lisuride and CQ 32-084 on rat feeding
      behaviour.
AB  - The influence on rat-feeding behaviour of lisuride and CQ 32-084, agonists at
      dopamine D2 receptors, was examined using two procedures. In a first series of
      experiments, the apparatus was an X-maze baited with food pellets where
      individual fasted rats were observed for 5 min. A number of parameters were
      recorded: latency to tasting and feeding, interval between tasting and feeding,
      total feeding time, and total grooming time. Lisuride (0.05 and 0.1 mg/kg) and CQ
      32-084 (0.05 and 0.5 mg/kg) behaved as stimulants of eating; lisuride (0.4 mg/kg)
      inhibited the phenomenon. Both drugs always antagonized grooming. Subsequently,
      when food intake was determined in the home cages of fasted animals lisuride
      reduced feeding at all doses during the first hour after treatment, while CQ 32
      084 had no effect. The data show that the two compounds display different
      activity on ingestive behaviour according to the dose and experimental model
      used. Discussion centres on the possible dependence of feeding enhancement in the
      X-maze on the anxiolytic activity exerted by low D2 autoreceptorial doses.

PMID- 1350682
TI  - Effects of yohimbine and idazoxan on motor behaviors in male rats.
AB  - Yohimbine, an alpha 2 adrenergic antagonist, facilitates copulatory behaviors in
      male rats. This facilitation may reflect nonspecific activation of behavior
      rather than a more selective activation of copulatory behaviors. The present
      experiments assessed the effects of yohimbine on locomotor behaviors at a dose
      (2.0 mg/kg) known to facilitate sexual behaviors. Experiment 1 used a computer
      pattern-recognition system to classify motor behaviors into specific acts and act
      groups. Male albino rats were tested in three conspecific conditions: estrous
      female, anestrous female, or no conspecific. Yohimbine decreased locomotor
      activity in all three conspecific conditions. Experiment 2 examined the effects
      of yohimbine (2.0 mg/kg) and amphetamine (1.0 mg/kg) on locomotor behavior in a
      photocell-equipped activity measurement system. Amphetamine increased and
      yohimbine decreased locomotor activity. Experiment 3 used the computer pattern
      recognition system to compare the effects of yohimbine and idazoxan, another
      alpha 2 adrenergic antagonist, on motor behaviors. Yohimbine and idazoxan both
      decreased activity but produced different patterns of behavioral change. The
      facilitatory effects of yohimbine on copulatory behaviors at a dose of 2.0 mg/kg
      are apparently not mediated by nonspecific activation of behavior.

PMID- 1350683
TI  - Comparative study of roles of the lobus parolfactorius and intermediate medial
      hyperstriatum ventrale in memory formation in the chick brain.
AB  - Two discrete areas of the chick brain, the intermediate medial hyperstriatum
      ventrale (IMHV) and lobus parolfactorius (LPO), were found to have different
      functions during the formation of memory for a 1-trial peck-avoidance paradigm.
      Glutamate, ouabain, and emetine, known to disrupt short-, intermediate-, and long
      term memory when injected into the IMHV, were injected into the cerebellum and
      LPO. All amnestic agents investigated produced amnesia when injected into the
      IMHV; only one of these agents produced amnesia when injected into the LPO, and
      none of the agents produced amnesia when injected into the cerebellum. The chick
      brain was also found to exhibit hemispheric asymmetries: The left IMHV and LPO
      were more sensitive to the amnestic agents than their corresponding right
      structure. From these data, hypotheses for the roles of these structures during
      memory are proposed.

PMID- 1350684
TI  - Late posttraining memory processing by entorhinal cortex: involvement of NMDA and
      GABAergic receptors.
AB  - The NMDA receptor antagonist, D-2-amino-5-phosphonopentanoic acid (AP5) (5
      micrograms) and the GABAA receptor agonist, muscimol (0.03 microgram) were
      infused bilaterally into the entorhinal cortex of rats 0, 90, 180, or 360 min
      after training in habituation to a novel environment or in step-down inhibitory
      avoidance. Animals were tested for retention 22 h after training in each task.
      AP5 and muscimol were amnestic for both tasks when given 90 or 180 min after
      training, but had no effect when given 0 or 360 min after training. In contrast,
      intraamygdala injections or AP5 or muscimol were amnestic when given 0 but not 90
      min after inhibitory avoidance training. The results indicate that the entorhinal
      cortex plays a late but important role in posttraining memory processing; this
      role involves glutamatergic NMDA receptors and is inhibited by GABAA receptors.
      The intervention of the entorhinal cortex in posttraining memory processing is
      subsequent, and could be secondary, to that of the amygdala and other limbic
      structures.

PMID- 1350685
TI  - [Benzodiazepines in anesthesiology. Clinical applications (II)].

PMID- 1350686
TI  - [Comparative study of vecuronium and atracurium at low doses in minor pediatric
      surgery under combined anesthesia].
AB  - To compare, the time of onset and time of recovery of muscular blockade after use
      of half doses of vecuronium and atracurium, we studied 18 children ASA I who were
      proposed for short lasting pediatric surgery and combined anesthesia. Patients
      were divided into two groups: group V (n = 10) was treated with a single dose of
      0.05 mg/kg of vecuronium and group A (n = 8) with 0.25 mg/kg of atracurium.
      Assessment of muscular relaxation was performed by measuring the
      electromyographic responses to a train of four stimuli applied to the cubital
      nerve at the level of the hypothenar eminence. We administered 0.02 mg/kg of
      atropine, 5 to 10 mg/kg of thiopental, and the muscular relaxing dose together
      with orotracheal intubation when the first stimulus of the train of four stimuli
      was blocked at 90% of its initial value (T90). Maintenance of the anesthetic
      level was performed with 50% of N2O-O2 without inhalational anesthetics. A caudal
      blockade was induced by 1 ml/kg of bupivacaine at 0.25%. We measured the
      following parameters of muscular relaxation: T90, T10 (time at which the 10% of
      the first stimulus reappears), T25 (time of clinical efficacy) and IR (index of
      recovery). Only 60% of patients (6 out of the 10 patients of vecuronium group and
      5 out of the 8 subjects of atracurium group) achieved the T90. This occurred 2.5
      +/- 0.7 min after vecuronium and 3.2 +/- 0.6 min after atracurium. T10 was 13.7
      +/- 4.1 min for vecuronium and 13.3 +/- 4.1 min from atracurium. T25 occurred
      18.2 +/- 6.5 min after vecuronium and 19.4 +/- 2.1 min for atracurium.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1350688
TI  - [Swiss Society of Medical Radiology. 79th annual meeting. Flims, June 12-13,
      1992. Abstracts].

PMID- 1350687
TI  - Mathematical models of complex dose-response relationships: implications for
      experimental design in psychopharmacologic research.
AB  - We develop a mathematical model to account for the complex relationship between
      drug dose and clinical response in psychopharmacologic research. The model
      specifies relationships among drug dose, drug bioavailability, pharmacokinetic
      factors, course moderators, clinical response and the heterogeneity of the
      disorder, and allows for the derivation of results that have implications for
      experimental design in psychopharmacologic research. These results form the basis
      for computer simulations which indicate that random assignment to two fixed doses
      is more powerful and less sensitive to heterogeneity than assignment to
      clinically determined doses. Fixed dose designs, however, tend to overestimate
      the magnitude of drug bioavailability-clinical response relationships. Clinically
      determined dose designs are useful in some experimental situations; their
      effectiveness is enhanced by systematically reducing the clinically determined
      dose. Larger dose reductions improve the ability to detect bioavailability
      clinical response relationships.

PMID- 1350689
TI  - Factors influencing urinary tract retention after elective open cholecystectomy.
AB  - We studied a retrospective cohort of 360 consecutive patients who had undergone
      elective cholecystectomy using general endotracheal anesthesia to determine risk
      factors associated with postoperative retention of the urinary tract. Male
      gender, increased age, a longer operating time and higher total doses of
      analgesic agents given postoperatively were each significantly associated with an
      increase in urinary tract retention. The use of postoperative intravenous patient
      controlled analgesia was associated with increased retention after controlling
      for other risk factors. Physicians should consider inserting a Foley catheter
      preoperatively in patients undergoing a cholecystectomy who are scheduled to
      receive postoperative patient controlled analgesia.

PMID- 1350690
TI  - Bypass surgery for aortitis syndrome: aortocarotid bypass with saphenous vein
      graft.
AB  - In seven patients with Takayasu arteritis, symptomatic cerebral ischemia was
      successfully treated by extracranial bypass surgery. We performed 14 surgical
      procedures, which included aortocarotid bypass, axilloaxillary bypass, carotid
      vertebral bypass, subclavian-carotid bypass, axillocarotid bypass, carotid
      carotid bypass, carotid-subclavian bypass, carotid-axillary bypass, and
      thyreocervical-carotid anastomosis. Among those the aortocarotid bypass was the
      most common procedure performed--six occasions in four cases. The others were
      less common procedures, each performed only one time. The saphenous vein was used
      for the graft in 12 of the procedures. An artificial graft made of Gore-Tex (6-mm
      inner diameter) was utilized in two cases. Patency of the grafts was adequate and
      no mortality or serious postoperative complication was encountered. Asymptomatic
      infarction developed in one patient. We analyze these procedures in detail and
      stress the usefulness of aortocarotid bypass with a saphenous vein graft.

PMID- 1350691
TI  - Selective adrenergic agonists and colon motility in monkeys.
AB  - Sympathetic stimulation during and after laparotomy and other surgical procedures
      may be a factor inducing postoperative ileus. In experiments conducted in fasting
      monkeys, the effects of the selective sympathetic agonists alpha 1
      (phenylephrine), alpha 2 (ST-91), beta 1 (dobutamine), and beta 2 (terbutaline)
      on colon contractile activity were measured. Strain gauges were implanted on the
      colon. Recordings were made for 1 hour (control) and then for an additional hour
      during continuous infusion by one of a range of doses of each drug
      (experimental). The drug doses were chosen to cover both physiologic and
      pharmacologic concentrations. All of the sympathetic agonists caused a dose
      dependent decrease in the frequency of colon contractions. The beta-agonists did
      so at a concentration that is sufficiently low to support a hypothesis that beta
      stimulation leading to inhibition of smooth-muscle contraction may play an
      important role in the genesis of postoperative ileus.

PMID- 1350692
TI  - Relationship between the cytolysins tenebrosin-C from Actinia tenebrosa and
      equinatoxin II from Actinia equina.
AB  - The chemical, physical and biological properties of the cytolysin tenebrosin-C
      from Actinia tenebrosa have been compared with those of equinatoxin II from
      Actinia equina. The two proteins are indistinguishable by reverse-phase and
      cation-exchange HPLC and capillary zone electrophoresis, and give similar peptide
      fragments upon cyanogen bromide cleavage (as judged by the chromatographic
      behaviour, ultraviolet absorption spectra, amino acid composition and N-terminal
      amino acid sequences of the peptides). Their cardiac stimulatory activities are
      identical, and their haemolytic activities are similar, with equinatoxin II
      having slightly greater activity. These data indicate that the two molecules are
      either identical in all 179 amino acid positions, or differ by no more than one
      or two residues. These findings are discussed in the context of the taxonomic
      relationship between the two species of sea anemone.

PMID- 1350693
TI  - How antibodies block HIV infection: paths to an AIDS vaccine.
AB  - We are beginning to understand the mechanism that envelope proteins of the human
      and simian immunodeficiency viruses use to gain entry into host cells. A vaccine
      that can elicit antibodies that bind to the viral epitopes involved in this
      process would thereby prevent HIV infection. This article outlines our progress
      in the development of possible candidates for AIDS vaccines.

PMID- 1350694
TI  - Studies on maternal transmission of scrapie in sheep by embryo transfer.
AB  - The technique of embryo transfer was used to investigate the maternal
      transmission of scrapie in sheep. Embryo donor ewes were experimentally infected
      with scrapie (all eventually developing the disease) and artificially inseminated
      six months later with semen from an uninfected scrapie-susceptible ram. Embryos
      were harvested five and six days after insemination and transferred by
      laparoscopy, unwashed, into recipient ewes which had been genetically selected
      for very low susceptibility to scrapie. Six of the 26 lambs born to these
      recipients developed scrapie.

PMID- 1350696
TI  - [Comparison of the effects of diltiazem and isradipine in adrenergic beta
      receptor blockade in patients with stable angina pectoris].
AB  - In 20 patients with stable angina II-III according to NYHA by means of ergometry
      the effect of short-term administration of dilthiazem (90 mg in three doses),
      placebo and isradipine (5 mg in three doses) in block of beta-receptors of the
      sympathetic nerve (metipranolol 3 x 10 mg/day) was compared. As compared with
      placebo, dilthiazem and isradipine retarded significantly the development of
      stenocardia, reduced the S-T depression in lead V5 and increased the total work
      output during ergometry. Based on the results of this and previous work (9) it
      may be stated that concurrent administration of metipranolol reduced the
      frequency of side-effects of isradipine and prevented the reflex rise of the
      heart rate following its short-terms administration. The authors conclude that
      starting treatment of stable angina with isradipine is safer and more effective
      in combination with metipranolol than when monotherapy is used. Dilthiazem must
      be administered with metipranolol carefully with regard to possible development
      of severe bradycardia and its suitable dose should be established by titration.

PMID- 1350695
TI  - Expression of the c-erbB-2 proto-oncogene product and nuclear DNA content in
      benign and malignant human breast parenchyma.
AB  - The expression of the c-erbB-2 proto-oncogene product was investigated
      immunohistochemically in 474 formalin-fixed and paraffin-embedded human breast
      tissue samples. The series included 32 benign and 26 hyperplastic lesions, 32
      carcinomas in situ and 384 invasive breast carcinomas, 107 of which were less
      than 1 cm in diameter. Cytometric DNA assessments were performed on
      histopathologically or cytodiagnostically identified cell nuclei, using image
      analysis. C-erbB-2 immunoreactivity was not seen in normal parenchyma or in
      benign and hyperplastic lesions. Mammary carcinomas in situ were more frequently
      immunoreactive (59%) than invasive neoplasms (23%). Invasive tumours more than 1
      cm in diameter immunoreacted more often (26%) than small invasive carcinomas
      (16%). C-erbB-2 expression in regional lymph node metastases was the same as in
      the corresponding primary tumours. Significant differences were observed between
      the c-erbB-2 expression in DNA diploid and aneuploid lesions; for carcinomas in
      situ the figures were 40% and 72%, respectively. Invasive carcinomas of DNA
      diploid type rarely showed c-erb-B-2 expression, irrespective of tumour size and
      nodal status (7-11%). DNA aneuploid tumours were more frequently immunoreactive
      with increasing levels during progression (32-41%). Our data indicate that
      genetically stable invasive mammary tumours seem rarely to express the c-erbB-2
      protein, even during progression, whereas genetically unstable invasive neoplasms
      frequently show c-erbB-2 immunoreactivity which increases during tumour
      progression.

PMID- 1350697
TI  - Onset and duration of action of vecuronium in the elderly: comparison with
      adults.
AB  - The onset and duration of action of vecuronium were studied in young adult (n =
      30; mean age 34 +/- 11.1 (s.d.) yr), middle-aged (n = 20; mean age 60 +/- 5.8 yr)
      and elderly patients (n = 30; mean age 80 +/- 4.6 yr) anaesthetised with
      thiopentone, nitrous oxide in oxygen and halothane. Neuromuscular block was
      monitored by applying the train-of-four (TOF) stimulation at 2 Hz to the ulnar
      nerve every 12 s. Half the patients in each group received 0.08 and the other
      half 0.12 mg kg-1 of the relaxant. The time to return of T1 (first response in
      the TOF sequence) to 25% of control was 28 +/- 5.2 (s.d.), 34 +/- 7.1 and 39 +/-
      10.2 min following 0.08 mg kg-1 dose (P less than 0.05 between the elderly and
      young adults) and 45 +/- 9.2, 48 +/- 6.2 and 69 +/- 19.2 min following 0.12 mg kg
      1 dose, respectively, in the three age groups (P less than 0.05 between the
      elderly and the other two groups). The recovery indices (time for 25-75% recovery
      of T1) after the 0.08 mg kg-1 was 9.6 +/- 3.4, 13.6 +/- 5.1 and 17.4 +/- 6.1 min,
      respectively (P less than 0.05 between the elderly and young adults). There was
      no significant difference in any of the parameters between the young adults and
      the middle-aged. The onset of block at each dose was not significantly different
      between the three age groups; however, the time to maximum effect was
      significantly shorter with the higher dose in the young and the middle-aged, but
      not in the elderly. Regression analysis of the data between age and the duration
      of action and recovery index suggested a significant prolongation (P less than
      0.05) of these parameters in the elderly.

PMID- 1350698
TI  - Outcome in untreated schizophrenia: a search for symptoms and traits with
      prognostic meaning in patients admitted to a mental hospital in the
      preneuroleptic era.
AB  - A cohort of schizophrenic patients consecutively admitted to a mental hospital
      for the first time in 1925 was investigated in search of symptoms and traits with
      prognostic meaning. Since Leonhard's diagnostic system was applied, cases with
      mixed symptoms and a favourable outcome were excluded as being neither
      schizophrenic nor manic-depressive. Owing to the admission policy then
      prevailing, cases with clinically less striking and socially less deleterious
      features were underrepresented. The sample (n = 70), so demarcated, was still
      considered fairly appropriate for the purpose of a differential study of outcome
      in nuclear schizophrenia with a life-long follow-up. The best outcome group
      consisted of 33% of the sample; 24% formed an intermediate group, and 43%
      profoundly deteriorated with continuous psychotic symptoms and a total loss of
      social function. Marriage before index admission was the only characteristic
      related to a favourable outcome. Nuclear schizophrenic symptoms, thought
      disturbance, blunted affect and all catatonic symptoms listed in DSM-III were
      related to an unfavourable outcome. When prognostic subgroups were compared
      pairwise, no favourable trait was detectable, and there were no decisive
      differences between the group with the best outcome and the intermediate group.
      When these 2 groups were compared with the group with worst outcome, however,
      significant differences arose with respect to unfavourable characteristics.
      Predictions using a discriminant analytic procedure yielded the same results. The
      hypothesis that affective and atypical signs would also have prognostic meaning
      in nuclear schizophrenia was disproved.

PMID- 1350699
TI  - [Gamma-glutamyltransferase and alcoholic hepatic disease].
AB  - Accepting the principle that Gama-gt values are elevated in alcoholic patients,
      the authors attempted to find out if that enzyme might be helpful in
      distinguishing alcoholics with or without hepatic morphologic lesion. 110
      alcoholic patients with and 57 without histologically proved hepatic lesion were
      studied. The authors conclude that a single determination of Gama-gt lacks
      specificity to detect, among the alcoholic individuals, those who already carry a
      morphologic, nonreversible lesion.

PMID- 1350700
TI  - Atrial fibrillation: current therapeutic approaches.
AB  - Atrial fibrillation is associated with potentially life-threatening strokes.
      Anticoagulation with warfarin or aspirin reduces the risk of embolic events in
      patients with chronic atrial fibrillation and mitral valve stenosis or other
      underlying heart disease. In patients with acute onset of atrial fibrillation,
      anticoagulation is not necessary before cardioversion. However, in patients with
      chronic atrial fibrillation, anticoagulation should be started three weeks before
      cardioversion and continued for four weeks after the return of normal sinus
      rhythm. Quinidine remains the agent most commonly used for medical cardioversion
      in patients who are hemodynamically stable. If a patient is hemodynamically
      unstable or the atrial fibrillation is not corrected with drug therapy, direct
      current electrical cardioversion has a high success rate. Antiarrhythmic
      (quinidine) therapy is often continued indefinitely to help maintain sinus
      rhythm.

PMID- 1350701
TI  - Diagnosis and management of the paranoid patient.
AB  - Patients with symptoms of paranoia often present to primary care physicians. The
      paranoia may range in severity from a mild and largely incidental finding to a
      psychotic symptom. In its more severe forms, paranoia may constitute the chief
      complaint or may interfere with the patient's ability to accept treatment for
      other medical conditions. After an assessment of the severity of the symptoms and
      consideration of an organic etiology, initial treatment is often begun with a
      supportive approach and the prescription of a neuroleptic medication.

PMID- 1350703
TI  - Arrhythmias during the acute phase of reperfusion therapy for acute myocardial
      infarction: effects of beta-adrenergic blockade.
AB  - In 107 patients with acute myocardial infarction, the incidence of ventricular
      arrhythmias during the acute phase of thrombolysis was examined by means of
      Holter monitoring. In patients with a patient infarct-related artery as assessed
      angiographically at 90 minutes, the occurrence of accelerated idioventricular
      rhythms was noted significantly more frequently than in patients with a permanent
      occluded vessel. This arrhythmia peaked in the first 180 minutes after the start
      of thrombolysis. In addition, single ventricular premature beats and runs of
      ventricular tachycardia were also more common in patients with successful
      reperfusion. The effects of acute intravenous administration of beta-blockers
      were examined in 66 patients without contraindications to this therapeutic
      approach. There were no differences in the occurrence of any type of rhythm
      disorders in patients with (n = 43) or without beta-blockade (n = 23). Thus
      ventricular arrhythmias particularly accelerated idioventricular rhythms, and
      single ventricular premature beats occur more frequently in patients with a
      patent infarct artery within the first 24 hours after thrombolysis. Acute
      intravenous beta-blockade does not appear to exert significant antiarrhythmic
      effects during this period.

PMID- 1350702
TI  - Exercise-induced asthma.
AB  - Exercise-induced asthma affects approximately 10 percent of the exercising
      population but often goes undiagnosed. Diagnosis is generally simple if the
      physician is aware of the subtle symptoms that may present during or after
      exercise. Preventive treatment, using a combination of exercise strategies and
      inhaled medications, is often successful. For patients with underlying chronic
      asthma that is exacerbated by exercise, long-term medication with preexercise
      doses is recommended.

PMID- 1350704
TI  - Chronic beta 1-blocker treatment and cardiac beta 2-adrenoceptor function.

PMID- 1350705
TI  - Habitual fish consumption, plasma phospholipid fatty acids, and serum lipids: the
      Tromso study.
AB  - We examined the cross-sectional relationships between the frequency of habitual
      fish consumption, plasma phospholipid fatty acids, and serum lipids and
      lipoproteins in 152 men and women. There was a significant association between
      fish consumption starting from 1 dish/wk and plasma n-3, n-6, and n-9 fatty
      acids. Plasma eicosapentaenoic acid (EPA; 20: 5n-3) reflected fish consumption to
      a greater extent than did docosahexaenoic acid (DHA;22:6n-3). Triglycerides
      decreased (P less than 0.05) with fish consumption. In multivariate analysis in
      which anthropometric and lifestyle factors were controlled for, EPA correlated
      inversely with triglycerides (P less than 0.05) and positively with high-density
      lipoprotein (HDL) cholesterol and apolipoprotein A-I (both P less than 0.001). In
      contrast, DHA did not correlate with triglycerides and showed negative
      associations to HDL cholesterol and apolipoprotein A-I (both P less than 0.001).
      Platelet phospholipid EPA, but not DHA, was associated with lower triglyceride
      and higher HDL-cholesterol concentrations (both P less than 0.05). This study
      suggests that long-term intake of small amounts of fish has biological effects,
      and that EPA and DHA have divergent relations with lipoprotein metabolism.

PMID- 1350706
TI  - Maintenance treatment for Crohn's disease: has the time arrived?

PMID- 1350707
TI  - Composite tumor of the main bile duct producing several regulatory peptides.
AB  - Herein we describe what is, to our knowledge, the first reported case of a
      composite tumor of the main bile duct with epiploon metastases. Glucagon,
      pancreatic polypeptide, and somatostatin-immunoreactive cells were demonstrated
      in these metastases, but not serotonin, gastrin, or insulin-immunoreactive cells.
      The clinical significance of the neuroendocrine cells in the present case is
      discussed.

PMID- 1350708
TI  - Breast cancer in men: risk factors with hormonal implications.
AB  - Cases included in a population-based case-control study of breast cancer in men
      were recruited from 10 geographic areas of the United States from 1983 to 1986.
      Controls, matched to cases on age and geographic area, were selected by random
      digit dialing for men under age 65 years and from Health Care Financing
      Administration files for older men. Results are based on responses from 227 cases
      and 300 controls to questions asked in a standardized personal interview. An
      increased risk of breast cancer was most strongly associated with undescended
      testes and was also related to orchiectomy, orchitis, testicular injury, late
      puberty, and infertility; and a decreasing trend in risk was observed with an
      increasing number of children. Relative risk estimates were also elevated in
      relation to a history of high blood cholesterol, rapid weight gain, benign breast
      conditions, and possibly obesity. These findings suggest that breast cancer in
      men develops in response to androgen deficiency associated with testicular
      dysfunction and under conditions associated with excess estrogen. Risk was also
      found to be elevated in men with a history of amphetamine use, diabetes, and
      cigar smoking and reduced in men with prior head trauma.

PMID- 1350709
TI  - Fenoldopam reverses cyclosporine-induced renal vasoconstriction in kidney
      transplant recipients.
AB  - Cyclosporine causes renal vasoconstriction and reduced renal blood flow that may
      contribute to chronic nephrotoxicity. This effect has not been consistently
      reversed by available pharmacologic agents. The efficacy of orally administered
      fenoldopam, a dopamine-1 (DA-1) agonist with renal vasodilator properties, was
      evaluated in six patients whose condition was stable 3 to 6 months following
      renal transplantation. Glomerular filtration rate (GFR) and effective renal
      plasma flow (ERPF) were measured by inulin and p-aminohippurate (PAH) clearances,
      respectively, at baseline, after the acute oral administration of 100 mg of
      fenoldopam, and following 3 weeks of chronic oral fenoldopam therapy (100 mg
      thrice daily). Mean ERPF increased from 3.15 +/- 0.17 mL/s/1.73 m2 (189 +/- 10
      mL/min/1.73 m2) at baseline to 3.48 +/- 0.17 mL/s/1.73 m2 (209 +/- 10 mL/min/1.73
      m2) 4 hours after acute administration of fenoldopam (P = 0.04). Urine flow rate
      and fractional excretion of sodium also increased after acute administration, but
      not significantly. Mean systolic (SBP) and diastolic blood pressure (DBP)
      decreased maximally by 18 and 6 mm Hg, respectively, and mean pulse rate
      increased maximally by 8 bpm between 75 and 90 minutes after both acute and
      chronic administration. GFR was unchanged following both acute and chronic
      administration. The increase in ERPF was not maintained to the end of the dosing
      interval during chronic administration, probably due to the short half-life of
      fenoldopam. However, the renal vasodilatory response was still observed 3 to 4
      hours after readministration of the drug following 3 weeks of oral dosing. Thus,
      fenoldopam significantly reverses the renal vasoconstriction caused by
      cyclosporine in renal transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350710
TI  - Study questions benefits of New York triplicate-prescription rule for
      benzodiazepines.

PMID- 1350711
TI  - Chest pain of undetermined origin. Proceedings of a symposium. Hot Springs,
      Virginia, October 3-6, 1991.

PMID- 1350712
TI  - The seventh annual Society for Surgery of the Alimentary Tract Ross Laboratories
      Residents and Fellows Research Conference. San Francisco, California, May 9,
      1992. Abstracts.

PMID- 1350713
TI  - Distinct responses of interleukin-6 and other laboratory parameters to treatment
      in a patient with polyarteritis nodosa--a case report.
AB  - The authors describe a patient in whom the serum levels of interleukin-6 (IL-6)
      and other laboratory parameters were monitored. The IL-6 and C-reactive protein
      (CRP) levels, which were extremely high before treatment, declined rapidly with
      administration of prednisolone. Rheumatoid factor, IgG, and platelets count
      declined more gradually. Thus, determination of the serum IL-6 level might be
      useful in diagnosing and monitoring polyarteritis nodosa.

PMID- 1350714
TI  - Healing of segmental grafts of digital pad skin in dogs.
AB  - Pad grafts would be indicated in instances of severe paw trauma when there has
      been loss of the major weight-bearing pads (ie, metatarsal and metacarpal pads)
      as well as loss of the digital pads. A practical technique for replacing pad
      tissue on the remaining paw tissue could avert limb amputation for lack of weight
      bearing tissue in the area. Small segmental digital pad grafts were placed in
      granulation tissue beds in dogs. Although the grafts were from thick pad skin,
      they healed well. However, intervening wound areas did not become covered with
      the heavier keratinized epithelium of the pads. The thinner, more rapidly
      growing, less keratinized epithelium from the wound edges covered most of the
      wound.

PMID- 1350715
TI  - The autonomic nervous system modulates dry air-induced constriction in the canine
      lung periphery.
AB  - To determine the modulatory role of the autonomic nervous system on dry air
      induced bronchoconstriction (AIB) in the canine lung periphery, we examined the
      effect of cholinergic, alpha- and beta-adrenergic, and total autonomic ganglionic
      blockade on AIB. Pretreatment with atropine significantly attenuated AIB by
      approximately 30%, indicating that AIB is partially mediated via a vagal reflex.
      Pretreatment with either phentolamine or propranolol did not affect AIB,
      indicating that alpha- and beta-adrenoceptors, respectively, were not activated
      in response to dry air challenge. In contrast, pretreatment with hexamethonium
      significantly potentiated AIB. In addition, exogenous vasoactive intestinal
      peptide (VIP), a potential neurotransmitter for the nonadrenergic-noncholinergic
      (NANC) inhibitory system, significantly inhibited AIB. We conclude that (1)
      neither alpha- or beta-adrenergic efferents are activated during dry air
      challenge, (2) total autonomic blockade potentiates the response to dry air, and
      (3) VIP attenuates AIB. Based on these observations, we speculate that NANC
      inhibitory activity may be stimulated during dry air challenge and antagonizes
      AIB.

PMID- 1350717
TI  - Chromium and high-density lipoprotein levels in men taking beta-blockers.

PMID- 1350716
TI  - Prevention of first bleeding in cirrhosis. A meta-analysis of randomized trials
      of nonsurgical treatment.
AB  - OBJECTIVE: To assess the effectiveness of beta-blockers and endoscopic
      sclerotherapy in the prevention of first bleeding and reduction of mortality in
      patients with cirrhosis and esophagogastric varices. DATA SOURCES: Pertinent
      studies were selected using MEDLINE (1980 to 1990), reference lists from
      published articles or reviews, and congress abstract lists. STUDY SELECTION:
      Randomized trials comparing beta-blockers or sclerotherapy with a nonactive
      treatment. Nine randomized clinical trials of beta-blockers and 19 trials of
      sclerotherapy were reviewed. Seven trials of beta-blockers and 15 of
      sclerotherapy were published as full papers. DATA EXTRACTION: Crude rates of
      bleeding and death in treated and control groups were extracted from each trial
      by three independent observers according to the intention-to-treat principle. The
      quality of published papers was systematically assessed and scored. DATA
      SYNTHESIS: The Mantel-Haenszel-Peto method was used for statistical evaluation of
      heterogeneity and for pooling of the results. No substantial heterogeneity was
      found, and the incidence of bleeding in trials of beta-blockers was significantly
      reduced (pooled odds ratio, 0.54; 95% CI, 0.39 to 0.74), particularly in patients
      with large or medium-sized varices or in those with varices and a hepatic vein
      pressure gradient above 12 mm Hg; however, only a trend toward reduced mortality
      was obtained. Sclerotherapy trials were highly heterogeneous in the direction of
      the treatment effects on both bleeding (pooled odds ratio, 0.6; CI, 0.49 to 0.74)
      and mortality (pooled odds ratio, 0.76; CI, 0.61 to 0.94). The quality of the
      trials and the rate of bleeding in the untreated groups were the major sources of
      heterogeneity. The favorable results of sclerotherapy were obtained in trials
      with high bleeding rates among controls; several of these trials had a low
      quality score. CONCLUSIONS: Beta-blockers may be recommended for prevention of
      first bleeding in cirrhotic patients with varices who have a high risk for
      bleeding. The effectiveness of sclerotherapy remains undetermined. Further trials
      in high-risk patients may prove useful if improved criteria to predict bleeding
      risk become available.

PMID- 1350718
TI  - Selective D2 receptor stimulation induces dyskinesia in parkinsonian monkeys.
AB  - Stimulation of D1 striatal receptors has been proposed as the main mechanism
      mediating levodopa-induced dyskinesia in Parkinson's disease. We used (+)-PHNO, a
      selective D2 agonist, as the only treatment in 6 cynomolgus monkeys made
      parkinsonian by repeated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      administration. All animals developed choreic dyskinesia after a mean treatment
      period of 12.8 days (range, 1-29). Administration of the D1 antagonist SCH-23390
      1 hour before administration of (+)-PHNO did not change the dyskinesia. These
      results indicate that drug-induced dyskinesia in a primate model of Parkinson's
      disease is not solely induced by D1 receptor activation.

PMID- 1350719
TI  - A histochemical study by light and electron microscopy of the distribution of
      dipeptidyl peptidase-IV activity in the human dental pulp.
AB  - This activity was demonstrated in blood vessels, fibroblast-like cells,
      odontoblasts and Schwann cells surrounding non-myelinated axons. It was present
      on both the luminal and abluminal plasma membrane of endothelial cells. The
      plasma membrane of fibroblast-like cells and their processes had patches of fine
      electron-dense end-product corresponding to DPP-IV activity, while the plasma
      membrane of odontoblasts was loaded with a consistent reaction product. DPP-IV
      activity in the non-myelin-forming Schwann cells was in the plasma membrane of
      the free surface in contact with the extracellular matrix as well as in the
      plasma membrane in close contact with the axolemma. The plasma membrane of
      Schwann cells producing myelin sheath had no positive reaction for DPP-IV. The
      DPP-IV activity in the plasma membrane of fibroblast-like cells and odontoblasts
      may be associated with fibronectin-mediated adhesion to collagen, whereas the
      membrane-bound DPP-IV activity in endothelium and non-myelin-forming Schwann
      cells may be involved in cleavage of neuropeptides of other biologically active
      peptides.

PMID- 1350720
TI  - Alcoholism detection markers in blood samples of road users.
AB  - Alcoholics as participants in road traffic are an international problem. In
      Germany a confiscated driving licence is only given back by the road traffic
      authorities to suspected alcoholics after a medico-psychological examination. The
      problem is: "How can alcoholics be detected among drunken road users." Traffic
      authorities use as a marker of alcoholism only the height of the blood alcohol
      concentration. The limit is a level of 1.6 g alcohol per kg blood, in some
      regions a level of 2.0 g/kg. Our studies show that the blood alcohol level is a
      very weak marker for alcoholism. Better markers are beside the GGT the alcohols
      methanol and isopropanol. They can be detected by congener alcohol analysis.
      Their concentrations are significant elevated by long-lasting drinking like it is
      typical for alcoholics.

PMID- 1350721
TI  - Evolution of the vertebrate Hox homeobox genes.
AB  - One of the most remarkable recent findings in developmental biology has been the
      colinear and homologous relationships shared between the Drosophila HOM-C and
      vertebrate Hox homeobox gene complexes. These relationships pose the question of
      the functional significance of colinearity and its molecular basis. While there
      was much initial resistance to the validity of this comparison, it now appears
      the Hox/HOM homology reflects a broad degree of evolutionary conservation which
      has reawakened interest in comparative embryology and evolution. The evolutionary
      conservation of protein motifs in many gene families (including those for growth
      factors, secreted and membrane bound signalling factors, adhesion molecules,
      cytoplasmic receptor kinases, nuclear receptors and transcription factors) has
      lead to speculation on the extent to which these homology relationships represent
      common developmental processes and underlying molecular mechanisms. Structural
      identifies in a protein may indicate the biochemical/molecular function that a
      protein plays in cellular and developmental processes, without reflecting a
      conserved role in a cascade of developmental events. However, the analysis of
      genes encoding transcription factors has provided evidence suggesting that there
      are gene complexes in arthropods and vertebrates which are true homologues and
      which may share common roles in the specification of regional identity along
      embryonic A-P axis. These genes comprise the Hox/HOM-C homeotic complexes. This
      review will detail some of the evidence for this proposed relationship and will
      speculate on the functional implications.

PMID- 1350722
TI  - Homeobox genes in vertebrate evolution.
AB  - A wide range of anatomical features are shared by all vertebrates, but absent in
      our closest invertebrate relatives. The origin of vertebrate embryogenesis must
      have involved the evolution of new regulatory pathways to control the development
      of new features, but how did this occur? Mutations affecting regulatory genes,
      including those containing homeobox sequences, may have been important: for
      example, perhaps gene duplications allowed recruitment of genes to new roles.
      Here I ask whether comparative data on the genomic organization and expression
      patterns of homeobox genes support this hypothesis. I propose a model in which
      duplications of particular homeobox genes, followed by the acquisition of gene
      specific secondary expression domains, allowed the evolution of the neural crest,
      extensive organogenesis and craniofacial morphogenesis. Specific details of the
      model are amenable to testing by extension of this comparative approach to
      molecular embryology.

PMID- 1350723
TI  - The encounter coupling model for beta-adrenergic receptor/GTP-binding protein
      interaction in the S49 cell. Calculation of the encounter frequency.
AB  - Experiments measuring epinephrine stimulation of the S49 cell have demonstrated
      that the rate of adenylate cyclase activation is partly dependent on the rate of
      turnover of epinephrine occupancy with respect to individual receptors.
      Specifically, it has been shown that a low occupancy of the full receptor
      population by epinephrine promotes a rate of adenylate cyclase activation
      significantly greater than that for a low number of receptors completely occupied
      by epinephrine with which the concentration of bound receptors is the same. This
      finding indicated that the interaction of individual receptors with GTP-binding
      protein (G) occurs on a time scale which is greater than the mean lifetime of the
      epinephrine-receptor complex; during this period of interaction (an "encounter"),
      a receptor can change its occupancy state in the presence of a high binding
      frequency agonist such as epinephrine. Here we present a general analysis, in an
      extension of the Collision Coupling Model of Tolkovsky and Levitzki (Biochemistry
      17: 3795-3810, 1978), of the consequences of encounters (rather than pure
      collisions) for the relationships of receptor occupancy, receptor-agonist complex
      lifetime, and receptor-agonist efficiency to G/adenylate cyclase activation.
      Using this "encounter coupling" model of receptor/G interaction, it is
      demonstrated from a theoretical standpoint that the net rate of G activation can
      depend in part on the agonist binding frequency. The predicted dependence is
      consistent with the data on which the model is based, in which high binding
      frequency increases the activation rate. A special case of the "encounter
      coupling model" allows calculation of the frequency of encounters by an analysis
      of a previous experiment using epinephrine in which the rate of adenylate cyclase
      activation was measured in response to a small number of fully occupied, highly
      efficient receptors. Using those results and the model developed here, the
      encounter frequency was found to be on the order of 100/min in the intact S49
      cell. This calculation relied on knowledge of the rate of inactivation of
      G/adenylate cyclase in intact cells. A method for the measurement of the
      adenylate cyclase inactivation rate is presented. Using this method, the
      adenylate cyclase inactivation rate constant was found to be between 0.8 and
      3.0/min.

PMID- 1350724
TI  - Low density lipoprotein ligand-receptor interactions in normal healthy
      individuals characterized by their XbaI apolipoprotein B DNA polymorphism.
AB  - A DNA restriction fragment length polymorphism (RFLP), observed with the XbaI
      restriction enzyme digestion of peripheral lymphocyte genomic DNA and a 3.5 kb
      probe 3' end of the apolipoprotein B gene, was investigated in 228 normal healthy
      males. Lipoprotein measurements were conducted on fasting plasma and related to
      the genotype; the X2X2 homozygotes (the X2 allele contains the enzyme cutting
      site) had significantly higher plasma cholesterol, low density (LDL) cholesterol
      and LDL apolipoprotein B. Thirty subjects (10 from each of the X1X1, X1X2 and
      X2X2 groups) were recalled and the LDL receptor activity measurements, conducted
      on peripheral venous blood lymphocytes, indicated no significant differences
      between the genotypes. However, when LDLs isolated from these individuals were
      assayed for ligand-receptor interaction with a human embryonic lung fibroblast
      cell line, significantly different maximum binding (Bmax) values in the X2 allele
      bearing individuals were observed. This paradoxically elevated in vitro binding
      and degradation of LDL from X2X2 subjects suggests that the elevated
      concentrations of LDL cholesterol observed with this genotype in vivo does not
      result from a defective ligand-receptor interaction directly related to this
      polymorphism.

PMID- 1350725
TI  - [Physician malpractice in unmonitored delegation of ear canal irrigation to a
      physician assistant].

PMID- 1350726
TI  - Providing Total Care. Proceedings of the 15th annual APON conference. Boston,
      Massachusetts, October 17-19, 1991. Abstracts.

PMID- 1350727
TI  - Imidazoline receptors: a new regulatory concept in blood pressure control.
      Symposium of the American Society of Hypertension meeting. New York, May 15-18,
      1991.

PMID- 1350728
TI  - Imidazoline receptors. A new concept in central regulation of the arterial blood
      pressure.
AB  - Clonidine-like antihypertensive substances bind to nonadrenergic imidazoline
      specific sites within the nucleus reticularis lateralis (NRL), their medullary
      privileged site of action. Rilmenidine, a new central antihypertensive agent, was
      tested in the anesthetized rabbit. For the same hypotensive effect, cumulative
      doses given intracisternally proved 50 times more active than of those given
      systemically. Idazoxan, an alpha 2-adrenergic antagonist structurally related to
      the imidazolines, given centrally as pretreatment proved more potent in
      preventing the hypotensive effects than the same molar dose of yohimbine. When
      injected within the NRL area of the anesthetized rabbit, rilmenidine, like
      clonidine, always exhibited a hypotensive effect. The influence of clonidine and
      rilmenidine upon the NRL noradrenergic neurons involved in the blood pressure
      regulation, and upon those of the locus coeruleus (LC) involved in the sedative
      effect was studied by differential voltammetry. It was observed that rilmenidine
      was two times more selective than clonidine in inhibiting the NRL, as opposed to
      LC, neuronal activity. In addition, binding experiments of tritiated clonidine to
      human cortical and NRL membrane preparations showed that rilmenidine, as compared
      to clonidine, has a two to three times higher selectivity for the imidazoline
      receptors. In conclusion, we are now able to discriminate between the mechanism
      of the hypotensive effect of imidazoline-like drugs and that of their sedative
      action. Rilmenidine is the first example of an hypotensive drug more selective
      for imidazolin preferring receptors than for classical alpha 2-adrenoceptors.

PMID- 1350729
TI  - Nature of [3H]rilmenidine binding to membranes of rat cerebral cortex.
AB  - The binding of [3H]rilmenidine to membranes of rat cerebral cortex was studied in
      order to ascertain which receptor populations this novel antihypertensive
      interacts with in the cortex. A catecholamine-sensitive, alpha 2-adrenoceptor
      binding site was identified which represented up to 50% of specific, 2 nmol/L
      [3H]rilmenidine binding and was displaceable by the catecholamines in the rank
      order epinephrine----norepinephrine----dopamine----isoproterenol. Some
      imidazolines such as clonidine, naphazoline, and idazoxan and the guanidino
      compound guanabenz completely and potently inhibited [3H]rilmenidine binding from
      both catecholamine-sensitive and -insensitive sites. The substituted imidazole
      and guanidine, cimetidine, and amiloride, respectively, showed no affinity for
      [3H]rilmenidine binding. The pharmacologic profile of the catecholamine
      insensitive [3H]rilmenidine site in rat cerebral cortex suggests it may be novel,
      as it has the features of an imidazoline-guanidino-oxazoline binding site.
      However, its identity requires further characterization.

PMID- 1350730
TI  - Characterization of imidazoline-guanidinium receptive sites in renal medulla from
      human kidney.
AB  - Previous studies showed that alpha 2-adrenergic receptors and imidazoline
      guanidinium receptive sites (IGRS) are colocalized in rabbit and human renal
      proximal tubule. In the present study we investigated the localization of these
      two binding sites in the renal medulla from human kidney. Binding studies
      performed with [3H]idazoxan (IGRS ligand) and [3H]rauwolscine (alpha 2-adrenergic
      ligand) showed that, in membrane preparations from renal medulla, the density of
      IGRS was 3.6-fold higher than that of alpha 2-adrenergic receptors (134 +/- 7 v
      37 +/- 5 fmol/mg protein, respectively). These data indicate that imidazoline,
      guanidinium, and oxazoline derivatives could induce their therapeutic effects
      through the interaction with IGRS and/or alpha 2-adrenergic receptors located not
      only in the renal proximal tubule but also in other segments of the nephron.

PMID- 1350732
TI  - Distinctive features of rilmenidine possibly related to its selectivity for
      imidazoline receptors.
AB  - Rilmenidine is an oxazoline derivative with antihypertensive activity which was
      developed to enhance the dissociation between the hypotensive and adverse effect
      profile of centrally acting agents. Experimental studies have indicated that
      rilmenidine is selective for both alpha 2-adrenoceptors (v alpha 1) and newly
      discovered nonadrenergic imidazoline receptors in the brain and in the periphery.
      In experimental studies, rilmenidine differs from clonidine in that it is more
      selective for imidazoline receptors than for alpha 2-adrenoceptors; at
      equihypotensive doses, rilmenidine causes less bradycardia and reduction in
      cardiac output, less sedation, and little or no antinociceptive action compared
      to clonidine. The hypotensive effects of rilmenidine are antagonised by idazoxan
      and yohimbine, but idazoxan (imidazoline structure) is six times more potent than
      yohimbine (a selective alpha 2-antagonist). In isolated renal proximal tubule
      cells, where imidazoline binding has also been shown, rilmenidine inhibits
      reabsorption of sodium. Clinical studies comparing 1 mg rilmenidine with placebo
      demonstrated significant reductions in blood pressure (BP) (61% rilmenidine v 23%
      placebo normalized to 160/90 mm Hg). The reduction in BP was not associated with
      classical alpha 2 side effects such as dry mouth or daytime drowsiness. Compared
      with clonidine (0.15 to 0.3 mg), equihypotensive doses of rilmenidine (1 to 2 mg)
      induced two to three times less dry mouth, daytime drowsiness, and constipation;
      no orthostatic hypotension was reported. Methyldopa (0.5 to 1 mg) v rilmenidine
      (1 to 2 mg) indicated a comparable reduction of BP with significantly less
      weakness, drowsiness, orthostatic dizziness, and dry mouth on rilmenidine; there
      was no evidence of the "clonidine withdrawal syndrome" on drug
      withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350731
TI  - Imidazoline binding sites in fat cells. Localization and pharmacologic
      differentiation from alpha 2-adrenergic receptors.
AB  - Studies were carried out to define the cellular distribution and pharmacologic
      properties of the nonadrenergic [3H]idazoxan binding sites in white fat cells
      from various species (the term "nonadrenergic [3H]idazoxan binding sites" [NAIBS]
      has been retained pending a final decision about their name). NAIBS having quite
      similar binding properties were found in human, rat, hamster, rabbit, and dog fat
      cells. NAIBS are located both in plasma membranes (25 to 35%) and in
      intracellular membranes corresponding to the crude mitochondrial fraction of
      adipose tissue (65 to 75% of the total number of NAIBS found in the particulate
      fraction), while alpha 2-adrenergic receptors are exclusively located on the
      plasma membrane. NAIBS have no affinity for catecholamines but have a noticeable
      affinity for some imidazolinic and guanidinic derivatives. NAIBS are different
      from the "imidazoline receptors" which bind [3H]para-aminoclonidine in central
      nervous system areas. A comparative structure affinity study was performed to
      delineate the respective affinities of various imidazoline derivatives towards
      NAIBS and alpha 2-adrenergic receptors and to try to find selective ligands for
      both sites. Binding properties of the two sites were clearly different. Moreover,
      chronic administration of idazoxan and RX821002 to adult rabbits (4 mg/kg,
      subcutaneously for 7 days), resulted in an up-regulation of alpha 2-adrenoceptors
      in fat cells while the number of NAIBS was unaffected by the treatment. There is
      no clear demonstration of an interaction between NAIBS and G-proteins, adenylate
      cyclase, or lipolytic function in fat cells. Further studies are required to
      define their putative role in fat cells.

PMID- 1350733
TI  - Rilmenidine: a novel approach to first-line treatment of hypertension.
AB  - Rilmenidine (RIL) is a novel antihypertensive drug selectively acting at the
      sites of imidazoline receptors. Compared with diuretics, beta-blockers, Ca2+
      antagonists and angiotensin converting enzyme inhibitors, the four major groups
      recommended by the US Joint National Committee as first-line antihypertensive
      drugs, RIL appears to meet the same criteria of efficacy, safety, and
      acceptability. Rilmenidine dose-dependently decreases blood pressure (BP), acting
      as a vasodilator by decreasing vascular resistance through inhibition of the
      adrenergic nervous system, even while the BP changes due to standing and
      exercise. In comparison with placebo, RIL significantly decreased BP. In double
      blind comparative trials versus first-line diuretics and beta-blockers, RIL
      normalized BP in approximately 60% patients, showing a similar efficacy to other
      drugs. In contrast with hydrochlorothiazide, RIL decreased total cholesterol and
      did not change plasma potassium levels. No tachyphylaxis was observed during long
      term treatment. Central side effects, which have contributed to the limitation of
      the use of alpha 2-agonists as second- or third-line therapy for hypertension,
      were significantly less frequent with RIL than with clonidine or methyldopa.
      Indeed, the incidence of dry mouth and drowsiness during double-blind comparative
      trials versus clonidine and methyldopa was significantly lower with RIL. This
      absence of central side-effects was confirmed in double-blind comparative trials
      versus hydrochlorothiazide and atenolol. In contrast with clonidine, no sodium
      retention or weight gain were observed during chronic treatment with
      RIL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350734
TI  - The development of polyanhydrides for drug delivery applications.
AB  - This paper reviews the development of the polyanhydrides as bioerodible polymers
      for drug delivery applications. The topics include design and synthesis of the
      polymer, physical properties, techniques to fabricate the polymer into drug
      delivery devices, evaluation of biocompatibility, and example applications of the
      polyanhydrides. Discussion of the interrelationship between the physical-chemical
      properties of the polyanhydrides, fabrication methods, and drug release rates is
      included. One section is devoted to a case study to provide a historical
      perspective of the development a polyanhydride-based drug delivery treatment from
      the conception of the idea to the final stages of human clinical trials. This
      section includes an outline of the extensive in vitro and in vivo testing that is
      necessary for development of a new material for biomedical applications.

PMID- 1350735
TI  - Corneal endothelial toxicity of dapiprazole hydrochloride.
AB  - A new adrenergic antagonist designed for topical use to induce pupillary miosis
      has been tested for direct toxicity on isolated rabbit corneal endothelium.
      Dapiprazole hydrochloride was perfused across endothelia in the specular
      microscope at concentrations from 1.25 micrograms/ml to 1000 micrograms/ml. No
      toxicity was observed, as determined by corneal thickness determinations over a 3
      hour perfusion period, until concentrations greater than 125 micrograms/ml were
      reached. At 250 micrograms/ml a swelling rate of 17.8 microns/hour occurred, and
      at 500 micrograms/ml the swelling rate was 17.1 microns/hour; with 1000
      micrograms/ml inducing a swelling rate of 23.3 microns/hour. It is evident that
      the drug concentration that reaches the endothelium after topical application has
      no toxic effect on the cornea, and that the drug should only be used as directed
      and not used as an anterior chamber perfusate.

PMID- 1350736
TI  - Fatty acid profiles of brain phospholipid subclasses of rats fed n - 3
      polyunsaturated fatty acids of marine or vegetable origin. A two generation
      study.
AB  - The effects of dietary n - 3 polyunsaturated fatty acids (PUFA) on fatty acid
      profiles of rat brain phospholipid subclasses as well as on heart
      phosphatidylethanolamine through two generations were examined: Three groups of
      rats were fed 20 weight% fat diets in which approx. 30% of the fatty acids were
      polyunsaturated, either 17% linoleic acid + 13% C20(-) + C22 polyunsaturates from
      fish oil or 17% linoleic + 13% alpha-linolenic acid from linseed oil or 30%
      linoleic acid. The rats of the two generations were killed as adults at 18 weeks
      of age. The results demonstrated that fish oil was a better source than alpha
      linolenic acid for incorporation of n - 3 PUFA into the examined phospholipids.
      This was seen both in brain and heart tissue and in both generations of rats. In
      the brain phosphatidylethanolamine (PE) and phosphatidylserine (PS) similar fatty
      acid profiles were found in 1st and 2nd generation, but fish oil was more
      efficient than 18:3(n - 3) in increasing the levels of 22:6(n - 3), 20:5(n - 3),
      22:5(n - 3) and reducing 20:4(n - 6) and 22:5(n - 6). Fatty acid profiles of
      phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP) and
      phosphatidylinositol-4,5-bisphosphate (PIP2) were affected by dietary fats. In
      PIP and PIP2 of 2nd generation rats 20:4(n - 6) was reduced from 36 to 29%
      following fish oil intake, whereas alpha-linolenic acid had no effects. The
      cholesterol/phospholipid ratio was not affected in the brain, neither was the
      degree of unsaturation of the phospholipids. In heart PE the highest levels of
      20:5(n - 3)(2%) and 22:6(n - 3) (36%) were observed following fish oil intake.
      However, in rats fed alpha-linolenic acid a considerable increase in the level of
      22:6(n - 3) was observed from the 1st (21%) to the 2nd generation (26%).

PMID- 1350738
TI  - [IX Congress of the Spanish Society of Parenteral and Enteral Nutrition. Cadiz,
      June 3-6, 1992. Abstracts].

PMID- 1350737
TI  - Formula alpha-linolenic (18:3(n - 3)) and linoleic (18:2(n - 6)) acid influence
      neonatal piglet liver and brain saturated fatty acids, as well as docosahexaenoic
      acid (22:6(n - 3)).
AB  - Saturated fatty acids can be synthesized de novo and play a role in determining
      properties of structural membranes. The effect of dietary essential fatty acids,
      linoleic acid (18:2(n - 6)) and alpha-linolenic acid (18:3(n - 3)), on the
      saturated fatty acid content of membrane phospholipid has not previously been
      considered in newborn nutrition. The studies report the effect of low (1% fatty
      acids) or high (4%) formula 18:3(n - 3) with low (16%) or high (30-35%) formula
      18:2(n - 6) on the saturated and unsaturated fatty acid composition of liver and
      brain structural lipid of piglets fed formula from birth for 15 days. A
      significant inverse relationship between the formula % 18:3(n - 3), but not
      18:2(n - 6), and the liver phospholipid palmitic acid (16:0) was found. This may
      indicate a possible effect of dietary 18:3(n - 3) on de novo synthesis of 16:0
      and requires further investigation. Monounsaturated fatty acids in both liver and
      brain were significantly lower in response to high 18:3(n - 3) and to high 18:2(n
      - 6) plus low 18:1(n - 9) in the formula. Liver phospholipid and brain total
      lipid % docosahexaenoic acid (22:6(n - 3)) were significantly higher when formula
      containing 4% rather than 1% 18:3(n - 3) was fed, suggesting that 1% 18:3(n - 3)
      may limit tissue (n - 3) fatty acid accretion. These results suggest that future
      studies of essential fatty acid requirements, specifically 18:3(n - 3), should
      consider possible influences on the saturated fatty acids which also play a
      functional role in tissue structural lipids.

PMID- 1350739
TI  - Chronic parastomal ulcers: spectrum of dermatoses.
AB  - Parastomal ulcers that develop after stoma surgery have reportedly been
      associated with recurrent inflammatory bowel disease and chronic infection. We
      report 13 patients with refractory parastomal ulcers, which occurred at a mean of
      11 years after surgery. Parastomal ulcers in eight patients were the result of
      dermatologic conditions (e.g., contact dermatitis, bullous pemphigoid, lichen
      sclerosus et atrophicus, eczema, or psoriasis) or contact ulcers from dermatitis
      of the skin around the stoma and faceplate pressure. These ulcers healed after
      treatment with topical medications at a mean of 4 weeks. Five patients with
      inflammatory bowel disease had pyoderma gangrenosum ulcerations, which healed
      with systemic treatment at a mean of 25 weeks. Thus nonpyoderma gangrenosum
      parastomal ulcerations that occur late after stoma surgery require early
      enterostomal therapy nursing intervention and dermatologic evaluation, since they
      respond rapidly to appropriate local therapy.

PMID- 1350740
TI  - Development of a lethal mast cell disease in mice reconstituted with bone marrow
      cells expressing the v-erbB oncogene.
AB  - An animal model for malignant mastocytosis is described in mice reconstituted
      with bone marrow cells expressing the v-erbB oncogene. The lethal mast cell
      disease is characterized by massive infiltration of bone marrow, spleen, and
      several other visceral organs by connective tissue mast cells, which normally
      reside in the skin and the peritoneal cavity. As is frequently found in malignant
      mastocytosis, the v-erbB-induced mast cell disease was accompanied in some
      primary recipients by an acute myelogenous leukemia (AML) that killed all
      secondary recipients regardless of whether the AML was already evident in the
      primary host. The infiltrating mast cells stained strongly positive with
      berberine sulfate, suggesting that they were terminally differentiated and in
      vitro they showed only a weak proliferative capacity. The leukemias were clonal
      but apparently of different origin than the malignant mast cells, implying the
      transformation of two independent cell populations. Leukemic cells expressed
      various myeloid-specific markers as well as the B220 antigen, normally associated
      with the B-cell lineage. However, the Ig heavy chain genes were still in germ
      line configuration. In culture, these cells proliferated in the absence of
      exogenous growth factors and had the capacity to differentiate into mature
      myeloid cells. Preliminary experiments suggest that v-erbB may use parts of a
      signal transduction pathway normally coupled to the c-kit receptor. The v-erbB
      induced malignant mast cell disease should provide a useful animal model for
      elucidating the cause for malignant mastocytosis in humans and to explore
      possible therapeutic strategies.

PMID- 1350741
TI  - Open versus laparoscopic cholecystectomy: a retrospective comparative study.
AB  - Two groups of 40 patients (31 females, 9 males), matched for age and body mass
      index, who underwent either elective open cholecystectomy (Group I) or elective
      laparoscopic cholecystectomy (Group II) have been studied retrospectively to
      detect differences in operating time, morbidity and mortality, hospital length of
      stay, and use of postoperative analgesics. The two groups of patients had almost
      identical histories of gallstone disease. The median operating time for the
      patients in Group I was 45 min (range 35-95) compared with 90 min (range 50-135)
      in Group II. An intraoperative cholangiogram was performed in 21 of the patients
      in Group I and 22 patients in Group II. There were no deaths in either group. The
      overall complication rate was 22.5% in Group I and 10% in Group II. Median
      postoperative length of stay was 5 days for Group I patients (range 1-19) and 2
      days for Group II patients (range 1-5). All Group I patients required
      postoperative intravenous or intramuscular opiates, while 10% of Group II
      patients did not require any analgesia at all and pain was controlled with oral
      analgesics alone in 16%. Median total morphine dose for Group I patients was 46.9
      mg (range 9.4-180), as compared with only 15.6 mg (6.2-37.5) for Group II
      patients. This study concludes that laparoscopic cholecystectomy led to less
      complications, shorter hospital length of stay, and minimal use of postoperative
      analgesia.

PMID- 1350742
TI  - Chronic leukaemias.
AB  - In recent years many subtypes of CLL and some CML variants have been recognized
      throughout the world by means of careful clinical, epidemiological,
      immunological, molecular biological and viral studies. Most striking has been the
      establishment of a close association between certain immunophenotypical subtypes
      of CLL and infection with HTLV-I and possibly HTLV-II. CLL has consistently been
      shown to have a strong genetic component and a low incidence among Asians, but a
      growing body of evidence also links this major leukaemia type with environmental
      factors including solvents, unidentified farming and other occupational
      exposures. In contrast, CML is characterized by few genetic associations,
      relatively homogenous world-wide distribution, greater frequency in Blacks than
      in Whites, little evidence of viral aetiology, and evidence that exposures to
      ionizing radiation, benzene and possibly other chemical agents are important
      aetiological factors. Most studies suggest that acquired rather than genetic
      factors are of greater importance in the aetiology of CML, but this conclusion is
      somewhat difficult to reconcile with the relatively small variation in incidence
      rates internationally. Common to both disorders in most populations are an
      increasing incidence with age, male predominance, and stability of incidence,
      survival and mortality over the years, exclusive of improved survival of CML
      following allogeneic bone marrow transplantation.

PMID- 1350743
TI  - Insulin, glucagon and somatostatin in fetal rat islets maintained free-floating
      in culture: immunocytochemistry and radioimmunoassay.
AB  - Fetal rat islets maintained free-floating in tissue culture represent a source of
      B-cells. Because we recently noted the occurrence of other cell types during long
      term tissue culture, this in vitro model was used to examine the possible
      development of non B-cells. The changes in the numbers and percentages of B, A
      and D-cells in vitro were estimated by counting the hormone-positive cells after
      immunocytochemical staining. Insulin, glucagon, and somatostatin contents were
      determined in extracts of the cultured tissue. The experiments described here
      showed that the cultured islets maintained their viability over a two-week
      culture period, as evidenced by the increase of both the number of B-cells per
      islet and the DNA content per islet. During the first few days of culture,
      immunocytochemically stained free-floating islets indicated the presence of rare
      A- and D-cells at the periphery of B-cells; thereafter, numerous A- and D-cells
      were seen interdigitating with B-cells. Expressed per islet, the number of A- and
      D-cells increased during the culture; within the endocrine cell population, the
      percentage of these cells increased with time, at the expense of the percentage
      of B-cells. The glucagon and somatostatin contents of the free-floating islets
      were also increased. These converging observations suggest that additional non B
      cells may have been produced by free-floating islets during long-term tissue
      culture.

PMID- 1350744
TI  - Differences in intrinsic efficacy of benzodiazepines are reflected in their
      concentration-EEG effect relationship.
AB  - 1. The relevance of EEG effect parameters as a measure of the central nervous
      system effects of benzodiazepines was evaluated. The concentration-EEG effect
      relationships of the benzodiazepine agonist midazolam, partial agonist
      bretazenil, antagonist flumazenil and inverse agonist Ro 19-4603 were quantified
      and compared with the intrinsic efficacy and affinity of these compounds at the
      gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex. 2. The
      pharmacokinetics and pharmacodynamics of the compounds were determined after a
      single intravenous bolus administration of 5 mg kg-1 midazolam, 2.5 mg kg-1
      bretazenil, 10 mg kg-1 flumazenil or 2.5 mg kg-1 Ro 19-4603 to male Wistar
      derived rats. In a separate experiment the distribution between blood,
      cerebrospinal fluid and brain concentrations of these compounds was determined. A
      sensitive assay was developed to measure bretazenil and Ro 19-4603 concentrations
      in small samples of biological fluids. 3. The benzodiazepine-induced changes in
      amplitudes in the 11.5-30 Hz frequency band, as determined by aperiodic analysis,
      was used as EEG effect measure. Concentration-EEG effect relationships were
      derived by a pharmacokinetic-pharmacodynamic modelling procedure and in the case
      of midazolam, bretazenil and Ro 19-4603 successfully quantified by the sigmoidal
      Emax model. Large differences in maximal effect of midazolam (Emax = 73 +/- 2
      microVs-1), bretazenil (Emax = 19 +/- 1 microVs-1) and Ro 19-4603 (Emax = -6.5 +/
      0.4 microVs-1) were observed, reflecting their differences in intrinsic
      efficacy. A close correlation was found between the EC50 values based on free
      drug concentration and receptor affinity as determined by displacement of [3H]
      flumazenil in a washed brain homogenate at 37 degrees C. In the concentration
      range of receptor saturation flumazenil did not produce any changes in the EEG
      effect measure.4. The study demonstrated that the change in amplitudes in the
      11.5-30 Hz frequency band of the EEG is a relevant measure of the pharmacological
      effect intensity of benzodiazepines, because it seems to reflect their affinity
      and intrinsic efficacy at the central GABA-benzodiazepine receptor complex.

PMID- 1350745
TI  - Interference of cetirizine with the late eosinophil accumulation induced by
      either PAF or compound 48/80.
AB  - 1. The effect of topical or systemic treatment with the histamine H1-receptor
      antagonist, cetirizine, on the rat pleural eosinophil accumulation induced by PAF
      or compound 48/80 was investigated. The number of pleural resident eosinophils
      increased 6 h after the intrathoracic (i.t.) injection of PAF (1
      microgram/cavity), peaked within 24 h and persisted significantly augmented for
      at least 96 h. Compound 48/80 (25 micrograms/cavity) also produced a long lasting
      pleural eosinophilia but this was first noted only 24 h after stimulation. 2.
      Intraperitoneal pretreatment with cetirizine inhibited eosinophilia induced by
      either PAF (ED50 = 19 mg kg-1) or compound 48/80 (ED50 = 14 mg kg-1) whereas
      meclizine, another histamine H1-receptor antagonist, was inactive. 3.
      Administered locally, cetirizine (5 and 15 micrograms/cavity) also dose
      dependently inhibited both PAF- and compound 48/80-induced eosinophilia,
      providing evidence that its inhibitory effect is not due to any action upon
      circulating eosinophils. Consistent with this result, incubation of isolated
      peritoneal eosinophils with cetirizine failed to modify in vitro eosinophil
      migration caused by PAF. 4. Since the late eosinophilia induced by PAF may depend
      on the synthesis of a transferable protein mediator, cetirizine was administered
      to donor or recipient rats in order to determine whether it interferes with the
      generation or with the expression of this protein. We showed that only the
      treatment of recipient rats abolished the transfer of the eosinophilotactic
      activity, indicating that cetirizine does not modify the generation but inhibits
      the expression of this activity. 5. Our findings indicate that cetirizine is able
      to inhibit eosinophil accumulation by acting locally. The mechanism is neither
      related to its recognized ability to antagonize histamine H,-receptors nor to a
      direct action upon circulating eosinophils.

PMID- 1350746
TI  - 5-Methylurapidil may discriminate between alpha 1-adrenoceptors with a high
      affinity for WB4101 in rat lung.
AB  - The alpha 1-adrenoceptors of rat lung with a high affinity for [3H]-prazosin were
      subdivided into two populations (high and low affinity sites) by WB4101 and 5
      methylurapidil but the proportions were different between both drugs. After
      pretreatment with chlorethylclonidine, WB4101 recognized only high affinity
      sites, while 5-methylurapidil still detected high and low affinity sites. These
      results indicate that alpha 1-adrenoceptors with a high affinity for WB4101 are
      not homogeneous in the rat lung, suggesting the possible existence of a new alpha
      1-adrenoceptor subtype in addition to alpha 1A and alpha 1B subtypes.

PMID- 1350747
TI  - The antagonism of benzodiazepine withdrawal effects by the selective
      cholecystokininB receptor antagonist CI-988.
AB  - The ability of a selective cholecystokininB (CCKB) receptor antagonist, CI-988,
      to block benzodiazepine withdrawal effects was examined in mice. The
      discontinuation of twice daily administration of diazepam (1 mg kg-1, i.p.)
      induced withdrawal anxiogenesis and a proconvulsant effect. In contrast, no such
      effects were seen following withdrawal from similar administration of CI-988.
      However, CI-988 dose-dependently (0.001-1.0 mg kg-1, s.c.) antagonized both the
      anxiogenesis and the proconvulsant effect following diazepam-withdrawal.

PMID- 1350748
TI  - Polymyalgia rheumatica and panarteritis nodosa.

PMID- 1350750
TI  - Golgi impregnated somatostatin immunoreactive neurons in lamina II of the rat
      spinal cord.
AB  - The morphology of somatostatin immunoreactive (SOM-I) neurons in lamina (L) II of
      the rat spinal cord was determined using a combination of Golgi impregnation and
      immunohistochemistry. Golgi-impregnated SOM-I neurons that resembled islet,
      stalked and other cells were observed. Islet cells are considered to be
      inhibitory interneurons while stalked cells are excitatory and are thought to
      relay information from primary afferent neurons to L I projection cells. The
      heterogeneous morphology of SOM-I neurons suggest they have diverse functions.

PMID- 1350751
TI  - AIDS is changing nature of doctor-patient relationship, doctors at CMA conference
      told.

PMID- 1350749
TI  - Effects of alpha-methyl-para-tyrosine on monoamine levels in the Japanese quail:
      sex differences and testosterone effects.
AB  - Experiments were performed to obtain more information on the regulation by
      steroids of catecholaminergic systems in the brain of Japanese quail. Dose
      response and time-response experiments were first performed to determine optimal
      conditions for measuring turnover in the quail brain. The norepinephrine and
      dopamine turnover were then estimated in microdissected brain nuclei of birds
      that were either sexually mature or gonadectomized or gonadectomized and treated
      with testosterone. Two major facts that bear direct relationship with the control
      of masculine reproductive behavior were demonstrated. On one hand, the dopamine
      turnover in the medial preoptic nucleus, a sexually dimorphic brain structure
      which is critically implicated in the control of copulatory behavior was much
      higher in male than in female quail irrespective of the hormonal condition of the
      birds. On the other hand, norepinephrine concentrations appeared to be higher in
      several nuclei of the female brain by comparison with males. These sex
      differences might represent part of the causal factors that underlie the sex
      dimorphism in reproductive behavior in quail.

PMID- 1350752
TI  - Generation of a small cell lung cancer variant resistant to lymphokine-activated
      killer (LAK) cells: association with resistance to a LAK cell-derived, cytostatic
      factor.
AB  - Cells of OS2-RA, a human small cell lung cancer line sensitive to lymphokine
      activated killer (LAK) cells, were repeatedly cocultured with human LAK cells.
      Fourteen cycles of the coculture produced a variant, termed OS2-RA-R, capable of
      growing successfully in the presence of LAK cells. OS2-RA-R showed a moderate
      resistance to lysis by LAK cells in 4-h 51Cr release assays. OS2-RA-R acted
      positively as a cold target for lysis of OS2-RA by LAK cells, suggesting no loss
      of the binding site for LAK cells on the cell surface of the variant. On the
      other hand, LAK cells were shown to produce a factor capable of suppressing the
      proliferation of OS2-RA and certain other cell lines but not lymphocytes.
      Interestingly, OS2-RA-R exhibited a substantial resistance to the cytostatic
      activity of LAK cell supernatants. The cytostatic factor, eluted at the 57-kDa
      fraction in gel filtration, showed no activity of interleukin 1, gamma
      interferon, transforming growth factor beta, or tumor necrosis factor. These
      results suggest that LAK cells exhibit antitumor activity through not only rapid
      cytolysis but also slow-acting cytokine production, and the successful growth of
      OS2-RA-R in a coculture with LAK cells is the result of acquiring resistance to
      these two different LAK cell phenomena.

PMID- 1350753
TI  - Resistance to N-benzyladriamycin-14-valerate in mouse J774.2 cells: P
      glycoprotein expression without reduced N-benzyladriamycin-14-valerate
      accumulation.
AB  - N-Benzyladriamycin-14-valerate (AD 198) is a highly lipophilic analogue of
      Adriamycin with novel cytotoxic mechanisms, greater in vivo antitumor activity,
      and the ability to circumvent multidrug resistance due to P-glycoprotein-mediated
      drug efflux or decreased topoisomerase II activity. To identify the mechanism(s)
      which may confer AD 198 resistance, J774.2 mouse macrophage-like cells were
      selected for growth in cytotoxic levels of AD 198 (AD 198R). AD 198R cells
      exhibited over-expression of the mdr1b (P-glycoprotein) gene, cross-resistance to
      Adriamycin and vinblastine, and potentiation of drug cytotoxicity by verapamil.
      However, net intracellular accumulation of AD 198 in AD 198R cells was unchanged
      compared to parental cells, while Adriamycin and vinblastine accumulations were
      reduced 40% and 95%, respectively. AD 198 was localized in the perinuclear region
      of the cytoplasm in both parental and AD 198R cells, with additional vesicular
      compartmentalization in AD 198R cells. Verapamil-induced reversal of AD 198
      resistance coincided with some drug redistribution from cytoplasmic vesicles, but
      without redistribution of AD 198 into the nucleus. These results suggest that AD
      198 resistance was not conferred through a P-glycoprotein-mediated reduction in
      intracellular drug accumulation but through other cytoplasmic mechanisms,
      including, but not limited to, drug compartmentalization.

PMID- 1350754
TI  - Deletion of chromosome 17p loci in breast cancer cells detected by fluorescence
      in situ hybridization.
AB  - Allelic loss of tumor suppressor genes on chromosome 17p has been implicated in
      the progression of breast cancer. This is in principle detectable by fluorescence
      in situ hybridization if the loss occurs by deletion. In order to determine if
      detectable deletions occur in primary breast cancer, we used dual-color
      hybridization with chromosome 17 pericentromeric and region-specific DNA probes
      to study 19 primary breast cancers. The copy numbers of 17 centromere and 17p13.1
      sequences were compared with the loss of heterozygosity (LOH) for probe YNZ22 at
      17p13.3 detected by restriction fragment length polymorphism. Nine of 11 cases
      showing LOH also showed the major population of nuclei with a deletion. The
      remaining two tumors with LOH were trisomic for both the centromere and 17p13.1
      cosmid. In contrast, seven of eight tumors without LOH had no deletions by
      fluorescence in situ hybridization. These data suggest that the dominant
      mechanism of allelic loss at 17p in breast cancer is a physical deletion and that
      analysis of deletions by fluorescence in situ hybridization is a rapid and
      sensitive approach to studying chromosomal aberrations.

PMID- 1350755
TI  - Taxol sensitizes human astrocytoma cells to radiation.
AB  - Taxol is a chemotherapeutic drug which acts by stabilizing microtubules,
      preventing normal mitosis and resulting in a block of the cell cycle at G2 and M.
      The drug is isolated from the yew, Taxus sp. L., and is currently being evaluated
      in a series of Phase II and Phase III clinical trials. Taxol blocks cells in the
      most radiosensitive phases of the cell cycle and thus could act as a cell cycle
      specific radiosensitizer. We report the results of combined taxol-radiation
      exposures in the human Grade III astrocytoma cell line, G18. Taxol is a potent
      inhibitor of G18 cell division; a concentration of 10 nM is cytostatic for a cell
      population observed for at least two doubling times. Cell survival curves for G18
      cells showed a significant concentration-dependent interaction between taxol and
      radiation. Treatment of G18 cells with a fixed taxol concentration and radiation
      dose showed the interaction to be dependent on the duration of taxol exposure and
      consequently the fraction of cells in the G2 or M phase of the cell cycle. The
      sensitizer enhancement ratio for 10 nM taxol at 10% survival is 1.8 and, for 1 nM
      taxol, it is 1.2. These results suggest that appropriate combinations of taxol
      have a more than additive interaction in human tissue culture and may have a role
      in clinical protocols.

PMID- 1350756
TI  - [Evaluation of the 3-stage alleviation of late cancer pain].

PMID- 1350757
TI  - Bilirubin covalently bound to albumin does not interfere with measurement of
      hepatic enzymes by dry chemistry methods (Kodak Ektachem).

PMID- 1350758
TI  - [The metabolic effects of beta-receptor blockers. What is of practical importance
      in antihypertensive therapy?].

PMID- 1350759
TI  - Characterization of multidrug-resistant pituitary tumor cells.
AB  - These studies were designed to investigate the role of P-glycoprotein in an
      endocrine cell line. Drug-resistant pituitary cells were obtained by growing
      GH4C1 cells in the presence of increasing concentrations of colchicine. Cells
      resistant to colchicine at 0.4 micrograms/ml, termed GH4C1/RC.4, exhibited the
      multidrug-resistance phenotype, as the LD50 values for colchicine, puromycin,
      actinomycin D, and doxorubicin were between 8 and 30 times greater than the
      corresponding values for the parental GH4C1 cells. Verapamil at 10 microM
      increased the sensitivity of GH4C1/RC.4 cells to colchicine, puromycin, and
      actinomycin D, almost completely reversing the drug resistance. Flow cytometry
      and fluorescence microscopy were used to demonstrate that GH4C1/RC.4 cells
      retained less rhodamine 123 than GH4C1 cells, and that the rate of efflux of
      rhodamine 123 was much faster for GH4C1/RC.4 cells. Immunocytochemical staining
      with a monoclonal antibody, C219, to the 170-kilodalton P-glycoprotein showed
      directly that GH4C1/RC.4 cells overexpress P-glycoprotein. We used drug-resistant
      pituitary cells to assess the possible role of P-glycoprotein in uptake and
      efflux of several hormones. At equilibrium, GH4C1 and GH4C1/RC.4 cells bound
      similar amounts of [125I]L-triiodothyronine and [125I]L-thyroxine, and verapamil
      did not alter either equilibrium binding or thyroid hormone efflux kinetics.
      Multidrug-resistant GH4C1/RC.4 cells retained less [3H]hydrocortisone than
      parental GH4C1 cells at equilibrium, and verapamil increased the equilibrium
      concentration of [3H]hydrocortisone 3.6-fold. The effect of verapamil was due to
      its ability to reverse multidrug resistance, since two other chemosensitizers,
      quinidine and vinblastine, increased [3H]hydrocortisone retention as effectively
      as verapamil but another calcium channel blocker, nifedipine, had no effect. The
      drug-resistant GH4C1/RC.4 line synthesized more GH (290%) and much less PRL (5%)
      than the parent. Hydrocortisone stimulated GH synthesis and inhibited PRL
      similarly in GH4C1 and GH4C1/RC.4 cells. The results show that the GH4C1/RC.4
      line is multidrug-resistant and overexpresses the 170-kilodalton P-glycoprotein
      and suggest that the P-glycoprotein pump contributes to hydrocortisone kinetics.

PMID- 1350760
TI  - Tamoxifen attenuates pulsatile growth hormone secretion: mediation in part by
      somatostatin.
AB  - Tamoxifen, a partial competitive antagonist to the estrogen receptor, is a potent
      inhibitor of the proliferation of experimental mammary carcinoma in the rat and
      is widely used clinically in the treatment of breast cancer. Blockade of estrogen
      receptors present on neoplastic cells represents the classic mechanism of action
      of tamoxifen, but the drug has a variety of other actions that may contribute to
      its antiproliferative properties. While it is recognized that estrogens play an
      important role in modulating pulsatile GH release, the effect of antagonists to
      sex steroid receptors on GH secretory dynamics has not previously been described.
      In the present study we examined the effect of tamoxifen on pulsatile GH
      secretion in free-moving adult male and female rats. The drug, when administered
      in a manner previously shown to be associated with antineoplastic activity,
      caused a marked suppression of the amplitude of spontaneous GH secretory bursts
      and significantly reduced mean 6-h plasma GH levels in both sexes compared to
      those in their respective peanut oil-injected controls. Inhibition of spontaneous
      GH pulses persisted for up to 7 weeks after tamoxifen administration in both
      sexes. Immunoneutralization of endogenous somatostatin in tamoxifen-treated male
      rats completely restored both GH pulse amplitude (121.6 +/- 9.5 vs. 62.5 +/- 13.5
      ng/ml in tamoxifen-treated rats given normal sheep serum; P less than 0.02) and
      mean 6-h plasma GH levels (53.3 +/- 6.6 vs. 17.9 +/- 3.6 ng/ml in normal sheep
      serum-treated rats; P less than 0.01) to levels observed in our peanut oil
      injected controls. These results demonstrate that 1) tamoxifen has potent
      inhibitory effects on pulsatile GH secretion; and 2) the blunting of GH pulse
      amplitude by tamoxifen is mediated at least in part by increased release of
      endogenous somatostatin. These findings motivate further investigation of the
      clinical significance of tamoxifen-induced suppression of GH secretion in
      relation to the antineoplastic activity of this commonly used drug.

PMID- 1350761
TI  - Purification and sequencing of molluscan insulin-related peptide II from the
      neuroendocrine light green cells in Lymnaea stagnalis.
AB  - The growth-controlling neuroendocrine light green cells of the freshwater snail,
      Lymnaea stagnalis, express a family of genes encoding structurally related, yet
      distinct, molluscan insulin-related peptides (MIPs). In the present study one of
      these peptides, MIP II, has been isolated and structurally identified. MIP II is
      a heterodimer of A and B chains connected by disulfide bonds. Both chains are N
      terminally blocked with pyroglutamate. After cleaving of the A and B chains and
      deblocking with pyroglutamate amino-peptidase their sequences have been
      determined as: A chain: pQRTTNLVCECCFNYCTPDVVRKYCY and B chain:
      pQSSCSLSSRPHPRGICGSNLAGFRAFICSNQNSPS. In comparison with the MIP II sequence
      based on complementary DNA studies, it is clear that the two C-terminal amino
      acid residues of the B chain are posttranslationally removed. In addition, the
      glutamic acid residue in A chain was recovered in very low yields during Edman
      degradation, suggesting that the residue may be posttranslationally modified.

PMID- 1350762
TI  - Modulation of glucocorticoid induction of stably transfected tyrosine
      aminotransferase gene constructs involves elements up-stream of the
      glucocorticoid-responsive element.
AB  - Previous studies have documented that the amount of agonist activity expressed by
      the antiglucocorticoid dexamethasone 21-mesylate (Dex-Mes) for tyrosine
      aminotransferase (TAT) induction in two rat hepatoma cell lines (Fu5-5 and HTC)
      is greater in Fu5-5 cells and could be varied in each cell line with changes in
      cell density. We have proposed that both phenomena are mediated by the binding of
      a trans-acting factor, the concentration or activity of which is lower in HTC
      cells. We have now used DNase-I hypersensitivity studies to identify a possible
      binding site for this factor at around -3.6 kilobases (kb) of the TAT gene. Fu5-5
      and HTC cells were then stably transfected with hybrid constructs either with
      (3.9TATCAT) or without (2.9TATCAT) this region of the TAT gene fused up-stream of
      a chloramphenicol acetyltransferase (CAT) reporter gene. High levels of Dex-Mes
      agonist activity for the induction of CAT activity in Fu5-5 cells were seen only
      with the 3.9TATCAT construct, indicating that the 0.97-kb region unique to this
      construct controlled the high levels of Dex-Mes agonist activity. Furthermore,
      variations in Fu5-5 cell density caused major quantitative changes in the amount
      of Dex-Mes agonist activity only in cells containing the 3.9TATCAT construct,
      consistent with the same 0.97-kb sequences also controlling the variations in Dex
      Mes agonist activity. Additional studies at high and low cell densities revealed
      that the modulation of Dex-Mes agonist activity for both the endogenous TAT gene
      and the transfected TAT/CAT gene was not due to changes in the start site of gene
      transcription. These studies both support our previous hypothesis that modulation
      of Dex-Mes agonist activity results from changes in a trans-acting factor and
      localize a necessary cis-acting element to sequences between -3.9 and -2.9 kb of
      the TAT gene. These studies, thus, define a potentially new element for
      glucocorticoid regulation of TAT gene transcription.

PMID- 1350763
TI  - Transfer of cadmium from a sandy acidic soil to man: a population study.
AB  - This population study included 230 subjects (age range 20-83 years) who consumed
      vegetables grown in kitchen gardens on a sandy acidic soil (mean pH approximately
      6.3). The study investigated the association between the Cd (cadmium) levels in
      blood and urine and the Cd concentration in the soil (range 0.2-44 ppm). Seventy
      six subjects were current smokers and 122 participants lived in a district with
      known Cd pollution. Urinary Cd in the 230 subjects averaged 8.7 nmole/24 hr,
      (range 1.3 to 47 nmole/24 hr) after age adjustment positively correlated with the
      Cd level in the soil; a twofold increase of the Cd concentration in the soil was
      accompanied by a 7% rise in urinary Cd in men (R2 = 0.05; P = 0.04) and by a 4%
      rise in women (R2 = 0.02; P = 0.05). Blood Cd averaged 11.5 nmole/liter (range
      1.8-41 nmole/liter) and was negatively associated with the Cd level in the soil.
      After adjustment for significant covariates (smoking and serum gamma-glutamyl
      transpeptidase in both sexes, and age and serum ferritin in women), a twofold
      increase in the Cd concentration in the soil was accompanied by a 6% decrease in
      blood Cd in men (R2 = 0.03; P = 0.09) and by a 10% decrease in women (R2 = 0.06;
      P less than 0.01). In conclusion, in a rural population, consuming vegetables
      grown on a sandy acidic soil, 2 to 4% of the variance of urinary Cd was directly
      related to the Cd level in the soil. The negative correlation with blood Cd, a
      measure of more recent exposure, was biased by the implementation of preventive
      measures in the polluted district.

PMID- 1350764
TI  - Gadolinium ion inhibits loss of metabolites induced by osmotic shock and large
      stretch-activated channels in bacteria.
AB  - Bacteria subjected to a hypotonic osmotic shock lose internal ions and also
      metabolites, without lysis of the cells. We show that the presence in the shock
      medium, at submillimolar concentrations, of the ion gadolinium, recently shown to
      block stretch-activated channels in Xenopus oocytes [Yang, X.-C. & Sachs, F.
      (1989) Science 243, 1068-1071], was sufficient to inhibit shock-induced release
      of metabolites such as lactose and ATP in Escherichia coli and ATP in
      Streptococcus faecalis. Moreover, gadolinium was observed, in patch-clamp
      experiments, to inhibit the giant stretch-activated channels of E. coli, S.
      faecalis. and Bacillus subtilis. Taken together, these data suggest that stretch
      activated channels are localized in the cytoplasmic membrane of Gram-negative and
      Gram-positive bacteria, where they control the efflux of osmotic solutes, thus
      probably playing a major role in the response to hypotonic osmotic shock.

PMID- 1350765
TI  - GHox-7: a chicken homeobox-containing gene expressed in a fashion consistent with
      a role in patterning events during embryonic chick limb development.
AB  - Homeobox-containing (HOX) genes are thought to be involved in the regulation of
      pattern formation and specification of positional information during vertebrate
      limb development. We report the isolation from a chick limb bud cDNA library of
      several overlapping chicken HOX cDNAs, which on the basis of their nucleotide and
      deduced amino acid sequences have been identified as corresponding to the chicken
      cognate of mouse Hox-7.1. The gene encoding these chicken (Gallus) HOX cDNAs has
      been designated GHox-7, and is a member of a family of vertebrate HOX genes that
      are highly similar in sequence to the Drosophila msh gene. GHox-7 encodes an mRNA
      transcripts of about 1.8-2.0 kb that is expressed at early stages of chick limb
      development. In situ hybridization analysis has revealed that GHox-7 is expressed
      in limb bud mesoderm in a temporal and spatial fashion. This is consistent with
      its involvement in specifying anterior positional identity and/or in the response
      of limb mesenchymal cells to the apical ectodermal ridge (AER), which directs
      polarized proximodistal limb outgrowth. At early stages (stages 20-21) of chick
      limb development when positional values along the anterior-posterior (A-P) axis
      are being specified, GHox-7 exhibits an asymmetric arc of expression extending
      from the anterior border of the limb bud to the mesenchymal cells directly
      subjacent to the AER.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350766
TI  - Expression of the murine Dlx-1 homeobox gene during facial, ocular and limb
      development.
AB  - We have analysed the expression pattern of the mouse homeobox containing gene Dlx
      1. This gene harbors a homeodomain related to that found in the Drosophila distal
      less (dll) gene. In addition to its expression in the developing forebrain, Dlx-1
      is transcribed in several structures containing cells of neural crest origin such
      as the facial mesenchyme and various elements of the peripheral nervous system.
      Dlx-1 transcripts are also detected in the differentiating retina and during limb
      morphogenesis, in the apical ectodermal ridge. The possible involvement of Dlx-1
      during facial, ocular and limb development is discussed.

PMID- 1350767
TI  - Chronic toxicity and carcinogenicity studies with the beta-adrenoceptor
      antagonist levobunolol.
AB  - The chronic toxicity and carcinogenicity of levobunolol, a nonselective beta
      adrenoceptor antagonist, was evaluated in Swiss mice and Wistar rats. The drug
      was administered in the diet to mice at 0, 12, 50, and 200 mg/kg/day for 80 weeks
      and to rats at 0, 0.5, 2, 5, 30, and 180 mg/kg/day for 2 years. In mice, uterine
      leiomyomas were present in 4 of 50 females at 200 mg/kg but not in any other
      group. The incidences of other tumor types, as well as pathologic findings, were
      comparable among groups. In rats, significant body weight gain suppression
      occurred at 5, 30, and 180 mg/kg. Brown discoloration of perianal fur and steel
      gray discoloration of hairless skin were evident in high-dose rats. A generalized
      steel-gray discoloration of internal organs and tissues occurred in the 30 and
      180 mg/kg groups. No other differences between treated and control groups were
      evident. The clinical relevance of the increased incidence of uterine leiomyoma
      in mice is questionable because it occurred only in one species at more than 200
      times the projected therapeutic dose.

PMID- 1350768
TI  - The ocular pathology of Norrie disease in a fetus of 11 weeks' gestational age.
AB  - The ocular pathology of Norrie disease was studied for the first time in a fetus
      of 11 weeks' gestation, following prenatal diagnosis using genetic markers for
      Norrie disease and elective abortion. The eyes were histologically normal, with
      no evidence of primary neuroectodermal maldevelopment of the retina, previously
      postulated to be the cause of the ocular changes. We believe that the retinal and
      other manifestations of Norrie disease are the result of a primary abnormality of
      vascular proliferation, probably in relation to persistent hyperplastic primary
      vitreous after approximately 14 weeks' gestation. We postulate that the ocular
      and otological effects of Norrie disease may be due to a genetically mediated
      abnormality of secretion of, or sensitivity to, angiogenic growth factors at
      endodermal-neuroectodermal interfaces during fetal and postnatal development.

PMID- 1350769
TI  - Alpha 1-adrenergic blockers.

PMID- 1350771
TI  - [Clinical evaluation of N-acetyl-beta-D-glucosaminidase on prediction of diabetic
      nephropathy].
AB  - To assess whether urinary N-acetyl-beta-D-glucosaminidase (NAG) could be used as
      a predictor of diabetic nephropathy, renal tubular enzymes such as NAG and gamma
      glutamyl transpeptidase (gamma GTP), albumin, total protein and beta 2
      microglobulin (BMG) in urine and/or serum were measured in various stages of
      diabetic nephropathy. As a predictor of diabetic nephropathy, urinary NAG was the
      most useful indicator among of them. Urinary gamma GTP had no clinical benefit on
      early detection of diabetic nephropathy although in cis-platin induced
      nephrotoxicity both urinary gamma GTP and NAG increased in parallel. Increase of
      urinary NAG appeared in diabetic patients prior to clinical proteinuria. With
      appearance of proteinuria, urinary NAG more increased. Urinary NAG correlated
      significantly with HbAlc and BMG in serum (sBMG). It is therefore needed for
      clinical application of urinary NAG as a predictor of diabetic nephropathy that
      control states of blood glucose in the patients should be considered. However,
      the results of sequential measurements of urinary NAG, sBMG and HbAlc in 78
      diabetic patients for 18-month period showed that only urinary NAG was a
      responsible factor for elevation of sBMG known as an indicator of deterioration
      of renal function. These results indicate that renal tubular damage may already
      exist in early-stage of diabetic nephropathy, and that increase of urinary NAG
      activity is a useful predictor of diabetic nephropathy.

PMID- 1350770
TI  - [Study of the signal transduction system of platelet alpha 2-adrenergic receptors
      in endogenous depression].
AB  - Researches in the mechanisms of action of antidepressant drugs have recently
      suggested that endogenous depression is related to an altered sensitivity of
      alpha-2 adrenergic receptors. Since this hypothesis is difficult to study in the
      central nervous system of human subjects directly, the alpha-2 adrenergic
      receptors on peripheral-blood platelets have been used as an accessible and
      convenient marker of the receptor function. Although the inhibition of adenylate
      cyclase, via the GTP-binding protein termed Gi, was believed to be the exclusive
      mechanism of alpha-2 adrenergic receptor action in the platelet, this concept has
      become less tenable. We have recently indicated that epinephrine stimulates
      phosphoinositide (PI) hydrolysis by activating alpha-2 adrenergic receptors in
      human platelets [Life Sci., 741-747 44 (1989)]. This method involves the
      measurement of the accumulation of [3H] -inositol-1-phosphate (IP-1) as an index
      of PI hydrolysis; lithium is added to inhibit the metabolism of IP-1, thus giving
      an enhanced signal. In addition, this PI response elicited by epinephrine was
      found to be inhibited in a concentration-dependent manner by treatment of
      platelets with dibutyryl cyclic AMP and 8-bromo-cyclic GMP which are known as
      potent inhibitors for platelet activation, and may therefore be a useful
      biochemical index for the study of the signal transduction system of alpha -2
      adrenergic receptors. In the present study, the platelet alpha-2 adrenergic
      receptor-mediated PI responses were assessed in 15 unmedicated patients with
      endogenous depression and 15 age -and sex-matched control subjects.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1350772
TI  - Effect of adenosine and inosine on carbon tetrachloride-induced liver damage in
      rats.
AB  - Liver damage induced in rats by carbon tetrachloride (CCL4) was obvious
      macroscopically as well as microscopically in stained sections. Levels of
      aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma
      glutamyl transpeptidase (gamma-GT) were also significantly raised. Adenosine and
      inosine effectively countered the damage when these were given before and during
      the period during which CCl4 produces the typical damage. The beneficial effect
      was seen in biochemical as well as pathological studies.

PMID- 1350774
TI  - Life-threatening bradycardic reactions due to beta blocker-diltiazem
      interactions.

PMID- 1350773
TI  - Some aspects of vascular pharmacology of frog (Rana tigrina).
AB  - Vascular autonomic receptors in amphibians exhibit difference from more evolved
      mammalian species. Vascular perfusion studies in frog indicate constrictions by
      prominent muscarinic but rudimentary nicotinic constrictive regulation by
      cholinergic systems. Difference from classical effect-patterns of pharmacological
      interventions, observed in the study, make room to visualise complexity of
      additional regulatory mechanisms.

PMID- 1350775
TI  - [Psoriasis and beta-blockade].
AB  - Psoriasiform skin eruptions during treatment with beta-adrenergic blocking drugs
      have recently attracted increasing attention and led the Bundesgesundheitsamt
      [German Office of Public Health] to publish general information on this issue.
      Today's knowledge on the clinical picture, pharmacology, and the pathogenesis is
      discussed, with reference to the latest experimental data. The blockade of
      keratinocyte beta-adrenergic receptors may play a key role in the aetiopathology
      of this unwanted side-effect.

PMID- 1350776
TI  - Cloning and characterization of the groESL operon from Bacillus subtilis.
AB  - The sequence of the 10 N-terminal amino acids of a Bacillus subtilis protein that
      cross-reacts with antibody to Escherichia coli GroEL was used to design a set of
      degenerate oligonucleotide probes. These probes identified a clone which carries
      almost the entire groESL operon from a B. subtilis subgenomic library. By
      chromosomal walking, an additional fragment carrying the 3' end of groESL and its
      flanking sequence was isolated. Sequence analysis revealed two open reading
      frames (ORFs) in the cloned DNA. The upstream ORF encodes a 10-kDa protein which
      has 47% amino acid identity with E. coli GroES. The downstream ORF encodes a 58
      kDa protein which is 62% identical to E. coli GroEL. A 2.1-kb groESL mRNA from B.
      subtilis was detected independently by Northern (RNA) blot analyses with a groES-
      and a groEL-specific probe. This demonstrated that groES and groEL are in an
      operon. The groESL promoter was located by using a promoter-probing plasmid, and
      the apparent transcription start site was mapped by primer extension analysis.
      The same promoter is utilized under normal and heat shock conditions. This
      promoter has the same features as a typical sigma A promoter. A strain in which
      the groESL operon was under the control of the sucrose-inducible sacB promoter
      was created. With this strain, it was possible to show that both groES and groEL
      are essential genes under both normal and heat shock conditions.

PMID- 1350777
TI  - Cloning, sequencing, mapping, and transcriptional analysis of the groESL operon
      from Bacillus subtilis.
AB  - Using a gene probe of the Escherichia coli groEL gene, a 1.8-kb HindIII fragment
      of chromosomal DNA of Bacillus subtilis was cloned. Upstream sequences were
      isolated as a 3-kb PstI fragment. Sequencing of 2,525 bp revealed two open
      reading frames in the order groES groEL. Alignment of the GroES and GroEL
      proteins with those of eight other eubacteria revealed 50 to 65% and 72 to 84%
      sequence similarity, respectively. Primer extension studies revealed one
      potential transcription start site preceding the groESL operon (S) which was
      activated upon temperature upshift. Northern (RNA) analysis led to the detection
      of two mRNA species of 2.2 and 1.5 kb. RNA dot blot experiments revealed an at
      least 10-fold increase in the amount of specific mRNA from 0 to 5 min
      postinduction, remaining at this high level for 10 min and then decreasing. A 9
      bp inverted repeat within the 5' leader region of the mRNA might be involved in
      regulation of the heat shock response. By using PBS1 transduction, the groESL
      operon was mapped at about 342 degrees.

PMID- 1350778
TI  - Biosynthetic precursors of deazaflavins.
AB  - The incorporation of 13C- and 14C-labeled precursors into 5-deaza-7,8-didemethyl
      8-hydroxyriboflavin (factor F0) was studied with growing cells of
      Methanobacterium thermoautotrophicum. 5-Amino-6-ribitylamino-2,4(1H,3H)
      pyrimidinedione was incorporated into the deazaflavin and into riboflavin without
      dilution. Tyrosine and 4-hydroxyphenylpyruvate were incorporated into the
      deazaflavin and into cellular protein. 4-Hydroxybenzaldehyde was not
      incorporated. A reaction mechanism is proposed for the formation of the
      deazaflavin chromophore from 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione
      and tyrosine or 4-hydroxyphenylpyruvate.

PMID- 1350779
TI  - Development of multipurpose peroxisomes in Candida boidinii grown in oleic acid
      methanol limited continuous cultures.
AB  - We have studied the development and metabolic significance of peroxisomes in the
      yeast Candida boidinii following adaptation of the organism to cultivation
      conditions which require the simultaneous presence and activity of two
      independent peroxisome-mediated pathways for growth. After the addition of
      methanol to oleic acid-grown cells at late exponentional growth, a number of new
      small peroxisomes developed which, apart from the presence of beta-oxidation
      enzymes, were characterized by the presence of enzymes involved in methanol
      metabolism (alcohol oxidase and dihydroxyacetone synthase). The latter proteins,
      however, were absent in the larger organelles which were originally present in
      the oleic acid-grown cells prior to the addition of methanol and which contained
      only enzymes of the beta-oxidation pathway. Subsequent experiments on cells from
      continuous cultures grown on a mixture of oleic acid and methanol at steady-state
      conditions revealed that both the enzymes of the beta-oxidation pathway and those
      involved in methanol metabolism were found in one and the same compartment. Thus,
      under these conditions the cells contained peroxisomes which were concurrently
      involved in the metabolism of two different carbon sources simultaneously used
      for growth. Our results indicated that the heterogeneity in the peroxisomal
      population of a single cell, observed in the transient state following the
      addition of methanol, is only temporary and due to heterogeneity among these
      organelles with respect to their capacity to incorporate newly synthesized matrix
      proteins.

PMID- 1350781
TI  - Characterization of a major polymorphic tandem repeat in Mycobacterium
      tuberculosis and its potential use in the epidemiology of Mycobacterium kansasii
      and Mycobacterium gordonae.
AB  - In this study, the occurrence of repeated DNA sequences in the chromosome of
      Mycobacterium tuberculosis was investigated systematically. By screening a M.
      tuberculosis lambda gt-11 gene library with labeled total chromosomal DNA, five
      strongly hybridizing recombinants were selected, and these contained DNA
      sequences that were present in multiple copies in the chromosome of M.
      tuberculosis. These recombinants all contained repeated sequences belonging to a
      single family of repetitive DNA, which shares homology with a previously
      described repeated sequence present in recombinant pPH7301. Sequences analysis of
      pPH7301 showed the presence of a 10-bp sequence that was tandemly repeated and
      invariably separated by 5-bp unique spacer sequences. Southern blot analysis
      revealed that the majority of the repeated DNA in M. tuberculosis is composed of
      this family of repetitive DNA. Because the 10-bp repeats are slightly
      heterogeneous in sequence, we designated this DNA as a major polymorphic tandem
      repeat, MPTR. The presence of this repeated sequence in various other
      mycobacterial species was investigated. Among the MPTR-containing mycobacterial
      species the chromosomal location of the repetitive DNA is highly variable. The
      potential use of this polymorphism in the epidemiology of mycobacterioses is
      discussed.

PMID- 1350782
TI  - Glu-537, not Glu-461, is the nucleophile in the active site of (lac Z) beta
      galactosidase from Escherichia coli.
AB  - The covalent intermediate formed during catalysis by the lac Z beta-galactosidase
      from Escherichia coli can be trapped by reaction of the enzyme with 2',4'
      dinitrophenyl 2-deoxy-2-fluoro-beta-D-galactopyranoside, thereby inactivating the
      enzyme. Kinetic parameters for this inactivation process with the holo- and apo
      enzymes have been determined. The intermediate so formed turns over only very
      slowly (t1/2 = 11.5 h) resulting in reactivation of the enzyme. The nucleophilic
      amino acid involved has been identified as Glu-537 by using a tritium-labeled
      inactivator to label the enzyme, then cleaving the labeled protein into peptides
      and purifying and sequencing the labeled peptide. This residue is conserved in
      five homologous beta-galactosidases and is different from that (Glu-461) proposed
      to be the nucleophile (Herrchen, M., and Legler, G. (1984) Eur. J. Biochem. 138,
      527-531) on the basis of affinity labeling studies with conduritol C cis-epoxide.
      A role for glutamic acid residue 461 as the acid/base catalyst is proposed and
      justified.

PMID- 1350780
TI  - Proline biosynthesis in Saccharomyces cerevisiae: molecular analysis of the PRO1
      gene, which encodes gamma-glutamyl kinase.
AB  - The PRO1 gene of Saccharomyces cerevisiae encodes the 428-amino-acid protein
      gamma-glutamyl kinase (ATP:L-glutamate 5-phosphotransferase, EC 2.7.2.11), which
      catalyzes the first step in proline biosynthesis. Amino acid sequence comparison
      revealed significant homology between the yeast and Escherichia coli gamma
      glutamyl kinases throughout their lengths. Four close matches to the consensus
      sequence for GCN4 protein binding and one close match to the RAP1 protein-binding
      site were found in the PRO1 upstream region. The response of the PRO1 gene to
      changes in the growth medium was analyzed by measurement of steady-state mRNA
      levels and of beta-galactosidase activity encoded by a PRO1-lacZ gene fusion.
      PRO1 expression was not repressed by exogenous proline and was not induced by the
      presence of glutamate in the growth medium. Although expression of the PRO1 gene
      did not change in response to histidine starvation, both steady-state PRO1 mRNA
      levels and beta-galactosidase activities were elevated in a gcd1 strain and
      reduced in a gcn4 strain. In addition, a pro1 bradytrophic strain became
      completely auxotrophic for proline in a gcn4 strain background. These results
      indicate that PRO1 is regulated by the general amino acid control system.

PMID- 1350784
TI  - Regulation of heme-controlled eukaryotic polypeptide chain initiation factor 2
      alpha-subunit kinase of reticulocyte lysates.
AB  - We have obtained highly purified preparations of the heme-controlled eukaryotic
      initiation factor 2 alpha-subunit (eIF-2 alpha) kinase (HCI) from rabbit
      reticulocyte lysates containing five different polypeptides. One of these is a 87
      kDa (p87) phosphopeptide which appears to show an autokinase activity. The
      controlled digestion with trypsin of HCI preparations leads to the suggestion
      that phosphorylation of p87 is not needed for kinase activity and, furthermore,
      that another 89-kDa polypeptide could be the kinase catalytic subunit. In
      agreement with this, monoclonal antibodies directed against p87 do not interfere
      with eIF-2 alpha kinase activity. Moreover, the anti-p87 antibodies and those
      directed against the mammalian 90-kDa heat shock protein recognize the same p87
      polypeptide from rabbit reticulocyte lysates. Upon incubation of the HCI
      preparation with hemin (5-10 microM), the eIF-2 alpha kinase is converted into an
      inactive form and appears to become associated with related peptides forming high
      molecular weight complexes which can be reversibly activated by 2
      mercaptoethanol. The maintenance of the integrity of the porphyrin ring is
      absolutely required for kinase inactivation and although the presence of metal
      ion is not essential, the iron and cobalt metalloporphyrins are more effective
      than protoporphyrin IX. The formation of the inactive form of HCI by hemin is
      prevented by either N-ethylmaleimide, monoclonal antibodies directed against p87,
      or phosphorylation of p87. The data strongly suggest that hemin regulates eIF-2
      alpha kinase activity by promoting formation of the inactive dimer HCI.p87 via
      disulfide bonds and direct binding of hemin. A model of HCI regulation is
      discussed.

PMID- 1350783
TI  - Identification of Gln726 in nidogen as the amine acceptor in transglutaminase
      catalyzed cross-linking of laminin-nidogen complexes.
AB  - The laminin-nidogen complex, the most abundant noncollagenous component of
      basement membranes, was recently shown to be a specific substrate for tissue
      transglutaminase (Aeschlimann, D., and Paulsson, M. (1991) J. Biol. Chem. 266,
      15308-15317). Saturation experiments to determine the number of amine acceptor
      site(s) indicated a single reactive Gln residue in nidogen and none in laminin.
      Murine nidogen was labeled with [3H]putrescine in the tissue transglutaminase
      catalyzed reaction, and two major radioactively labeled fragments, T70 and T40,
      were isolated after limited trypsin digestion. NH2-terminal sequencing showed
      that T40 is contained in T70 and corresponds to the rodlike structure of nidogen,
      made up of epidermal growth factor-like repeats. Three radioactively labeled
      peptides, obtained by extensive trypsin digestion of reduced and alkylated T40,
      were sequenced. In all a single residue, Gln726, was found to contain label.
      Sequencing of additional peptides, obtained after further treatment of the
      largest radioactively labeled peptide with endoproteinase Asp-N, gave the same
      result. Gln726 is located in an exposed loop between the second and the third EGF
      like repeat in nidogen. This site is also conserved in the human sequence.

PMID- 1350785
TI  - Purification and characterization of the neu/erb B2 ligand-growth factor from
      bovine kidney.
AB  - A neu/erb B2 ligand growth factor (NEL-GF) was purified to homogeneity from
      bovine kidney by a procedure involving ammonium sulfate fractionation (35-70%
      saturation) followed by sequential column chromatography on DEAE-cellulose
      (DE52), Sulfadex (sulfated Sephadex G-50), heparin-Sepharose 4B, and Superdex 75
      (fast protein liquid chromatography). NEL-GF was found to be a 25-kDa polypeptide
      according to the analysis by gel filtration on Superdex 75 and 10% sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. NEL-GF stimulated the tyrosine
      specific autophosphorylation of the neu/erb B2 gene product purified by
      immunoabsorbent and tyrosine-specific phosphorylation of the neu/erb B2 gene
      product in intact dihydrofolate reductase (DHFR/G-8 cells (NIH 3T3 cells
      transfected with rat c-neu). NEL-GF also down-regulated the cell surface neu/erb
      B2 gene product in DHFR/G-8 cells. NEL-GF was mitogenic toward NIH 3T3 cells,
      DHFR/G-8 cells, A431 cells (human epidermoid carcinoma cells), and SK-BR-3 cells
      (human breast carcinoma cells) but inactive toward bovine aorta endothelial
      cells. NEL-GF was sensitive to 0.1% trifluoroacetic acid but resistant to 5% beta
      mercaptoethanol and appeared to be distinct from a neu protein-specific
      activating factor (Davis, J. G., Hamuro, J., Shim, C. Y., Samanta, A., Greene, M.
      I., and Dobashi, K. (1991) Biochem. Biophys. Res. Commun. 179, 1536-1542) and a
      30-kDa glycoprotein which competed with a monoclonal antibody for binding to the
      neu/erb B2 gene product (Lupu, R., Colomer, R., Zugmaier, G., Sarup, J., Shepard,
      M., Slamon, D., and Lippman, M. E. (1990) Science 249, 1552-1555).

PMID- 1350786
TI  - A mutation in GroEL interferes with protein folding by reducing the rate of
      discharge of sequestered polypeptides.
AB  - GroEL140, a mutant Escherichia coli chaperonin unable to support bacteriophage
      lambda head assembly, was purified to near homogeneity and compared to wild type
      GroEL (cpn60). GroEL140 exhibited a 1.5-fold lower ATPase activity relative to
      the wild type protein. The hydrolysis of ATP by both polypeptides was fully
      inhibited by an excess of ATP gamma S and partially inhibited by ADP and 5'
      adenylylimidodiphosphate, suggesting that adenine nucleotides display different
      affinities for the ATP binding site of chaperonins. GroEL140 was more sensitive
      to trypsin digestion compared to wild type GroEL indicating that the mutation
      destabilized the conformation of the mutant. The proteolytic susceptibility of
      both chaperonins was similarly enhanced upon addition of ATP, ADP or non
      hydrolyzable ATP analogs, providing evidence (i) of a conformational change in
      the chaperonin structure which is likely to drive the protein discharge process,
      and (ii) that hydrolysis of ATP is not required to achieve topological
      modifications. GroEL140 retained its ability to bind non-native ribulose
      bisphosphate carboxylase/oxygenase (Rbu-P2-carboxylase), but released bound
      proteins upon addition of ATP and GroES (cpn 10) 6-7-fold less efficiently
      compared to GroEL. This functional defect was shown to be related to a
      suboptimal, but not an absence of, interaction with GroES since (i) GroEL140 and
      GroES were unable to form a complex isolatable by size exclusion chromatography,
      and (ii) increasing the incubation time or the concentration of GroES enhanced
      the amount of refolded Rbu-P2-carboxylase discharged from GroEL140-Rbu-P2
      carboxylase binary complexes. Pulse-chase experiments involving a double
      immunoabsorption technique confirmed that Rbu-P2-carboxylase remained associated
      two times longer with GroEL140 than with GroEL in vivo.

PMID- 1350787
TI  - Liver giant mitochondria revisited.
AB  - AIMS: To examine the correlation between the severity of alcohol induced liver
      damage and the presence of intracytoplasmic red bodies (defined as periodic acid
      Schiff diastase negative, globular, hyaline cytoplasmic inclusions larger in size
      than the hepatocyte nucleolus). To investigate the incidence of intracytoplasmic
      red bodies (ICRBs) in non-alcoholic liver disease. METHODS: Liver biopsy
      specimens from 53 patients with alcoholic liver disease and 50 patients with a
      variety of nonalcohol related liver diseases were examined by light microscopy
      for the presence of ICRBs. For the 53 patients with alcoholic liver disease an
      assessment of recent alcohol consumption was made indirectly from measurements of
      red cell volume (MCV) and plasma gamma-glutamyl transferase (GGT). In addition,
      10 liver biopsies with alcohol induced changes and ICRBs were examined by
      electron microscopy for the presence of mitochondrial aberrations including
      enlargement. RESULTS: ICRBs were detected in 18 of the 53 liver biopsy specimens
      showing alcohol induced changes, and were more abundant in those showing more
      advanced changes. Those patients whose liver specimens contained ICRBs were found
      to have a significantly higher mean plasma GGT activity and mean MCV than those
      individuals whose liver biopsy specimens did not contain ICRBs. Two of the 50
      liver biopsy specimens showing non-alcohol induced changes contained ICRBs. Giant
      mitochondria were not detected by electron microscopy, but this may reflect
      sampling. CONCLUSIONS: The results of this study indicate that ICRBs are
      definitely associated with alcoholic liver disease and are more likely to be
      found in liver biopsy specimens showing more advanced alcohol induced damage, and
      when recent alcohol consumption has been high.

PMID- 1350788
TI  - PCNA and Ki67 expression in breast carcinoma: correlations with clinical and
      biological variables.
AB  - AIMS: To investigate the expression of two cell cycle related antigens
      (proliferating cell nuclear antigen (PCNA) and Ki67 related antigen) in a series
      of breast cancers; and the possible correlations between the PCNA and Ki67
      labelling indexes (PCNA-LI and Ki67-LI) and their associations with other
      biological and clinicopathological variables. METHODS: Ninety six ductal and 10
      lobular carcinoma specimens were investigated. Samples were fixed in formalin and
      in Methacarnoy for localisation of PCNA. Ki67 was immunostained on frozen
      sections. The PCNA-LI and Ki67-LI were evaluated in relation to tumour size,
      mitotic count, histological grade, nodal state as well as receptor content and
      altered expression of the p53 gene. RESULTS: PCNA-LI did not correlate with Ki67
      LI, nor was it associated with any other variable examined. A high KI67-LI (above
      the median value of 13.5) was associated with high grade and mitotic count,
      negative receptor content, and altered expression of the p53 gene, but not with
      other variables. CONCLUSIONS: The PCNA-LI does not seem to be a substitute for
      the Ki67-LI in evaluating the growth fraction in breast cancer.

PMID- 1350789
TI  - c-erbB-2 oncogene product expression and prognosis in gastric carcinoma.
AB  - The prognostic value of c-erbB-2 protein expression was assessed retrospectively
      in 87 "curative" gastrectomy specimens from patients with gastric carcinoma.
      Tumours were stained immunohistochemically with the specific antibody 21N. Eight
      (9%) cases had strong membrane staining, all of which were of the intestinal
      type, and lymph node metastases, which showed concordance of staining in seven
      cases. In contrast to studies in breast cancer, positive cases showed a trend
      towards better five year survival, but this did not reach significance.

PMID- 1350790
TI  - erbB2 expression in breast and other human tumours.

PMID- 1350791
TI  - Antiallergic effect of epinastine (WAL 801 CL) on immediate hypersensitivity
      reactions: (II). Antagonistic effect of epinastine on chemical mediators, mainly
      antihistaminic and anti-PAF effects.
AB  - Anti-histamine and anti-PAF effects of epinastine were tested in rats, guinea
      pigs and rabbits. Epinastine showed a potent histamine H1-blocking effect, but
      the potency was slightly less than that of ketotifen in histamine-induced
      contraction of guinea pig ileum and histamine-induced cutaneous reactions in
      rats. In histamine-induced dye leakage into the nasal cavity tested in rats, the
      drug was slightly more potent than ketotifen and azelastine. Epinastine as well
      as ketotifen suppressed rabbit platelet aggregation induced by PAF at higher
      concentrations compared with WEB 2086, a specific PAF-antagonist. In the
      bronchospasm induced by PAF in guinea pigs, epinastine was more effective than
      ketotifen in inhibiting the bronchoconstriction, while it showed no remarkable
      effect on the hypotension induced by PAF. Epinastine caused a potent antagonistic
      effect on LTC4-induced contraction of isolated guinea pig trachea. In conclusion,
      the potent anti-histamine, anti-PAF and anti-LT effects of epinastine may
      significantly contribute to its antiallergic activity.

PMID- 1350792
TI  - Effects of taxol on the macrophage function. Interactions with some immunological
      parameters.
AB  - The effects of Taxol on some immunological parameters were investigated, in
      vitro, in the murine macrophage cell line J774.1. Mitochondrial dehydrogenase
      activity and (3H) TdR incorporation were shown to be increased in Taxol treated
      cells. Likewise, Taxol induced TNF alpha secretion. But Taxol seemed to be a weak
      inducer of the two interleukins IL-1 and IL-2, since their detection occurred
      late in the cell culture supernatants.

PMID- 1350793
TI  - Abnormalities of glucocorticoid metabolism and the renin-angiotensin system: a
      four-corners approach to the identification of genetic determinants of blood
      pressure.
AB  - AIM: To assess the feasibility and utility of a new method to identify factors
      associated with increased predisposition to high blood pressure in young people.
      SUBJECTS: Eight hundred and sixty-four people aged 16-24 years and their parents.
      SETTING: Ladywell Medical Centre, Edinburgh, Scotland, UK. METHOD: Blood pressure
      was measured in 864 young adults and in both of their parents. Four groups of
      approximately 50 offspring were selected from the corners of a scatter diagram,
      with offspring blood pressure scores on one axis and combined parental blood
      pressure scores on the other. Blood and urine samples were taken for biochemical
      and genetic analyses. RESULTS: Two groups of offspring had parents with high
      blood pressure and two groups had parents with low blood pressure. When parental
      blood pressure was low, comparison of offspring with high and low blood pressure
      revealed significantly higher mean body mass index in offspring with high blood
      pressure, but no significant elevation of biochemical or hormonal variables. When
      parental blood pressure was high, comparison of offspring with high and low blood
      pressure also revealed a significant difference in body mass index, but in
      addition, offspring with high blood pressure and high parental blood pressure had
      higher levels of angiotensinogen, cortisol and 18-OH corticosterone. Restriction
      fragment length polymorphism analysis revealed that 27% of offspring at the
      greatest genetic risk (high personal and parental blood pressure) were homozygous
      for the larger allele of the glucocorticoid receptor gene compared with only 9%
      of those at lowest genetic risk (low personal and parental blood pressure).
      CONCLUSION: The combined biochemical and genetic findings suggest that
      abnormalities of glucocorticoid metabolism and the renin-angiotensin system may
      help to explain genetic predisposition to high blood pressure. The new sampling
      method is practicable and could be applied to the investigation of other
      continuously distributed variables which show familial aggregation.

PMID- 1350794
TI  - Properties of amino acid neurotransmitter receptors of embryonic cortical neurons
      when activated by exogenous and endogenous agonists.
AB  - 1. The properties of receptors for amino acid neurotransmitters expressed by
      developing cortical neurons were studied with the use of whole-cell recording in
      the intact cerebral cortex of embryonic turtles in vitro. The inhibitory agonist
      gamma-aminobutyric acid (GABA) and the excitatory agonist glutamate were focally
      applied to single cells under voltage clamp, and the ionic dependence, voltage
      dependence, and pharmacological sensitivity of the responses were characterized.
      The responses mediated by a glutamate receptor subtype, the N-methyl-D-aspartate
      (NMDA) receptor, produced by glutamate and by evoked release of an endogenous
      excitatory agonist, were compared further. Fluctuation analysis was used to
      characterize the properties of the NMDA channels and the mechanism of action of
      receptor antagonists. 2. When postmitotic neurons first appeared at stage 15, all
      neurons tested responded to GABA with a current that reversed at the equilibrium
      potential for chloride ions and that was sensitive to the GABAA receptor
      antagonist bicuculline methiodide (BMI). As development proceeded, an increasing
      proportion of neurons also responded with a BMI-insensitive current that reversed
      near the equilibrium potential for potassium ions. This current was blocked by
      the GABAB receptor antagonist 3-amino-2-propyl phosponic acid (phaclofen). The
      GABAB agonist baclofen, however, failed to produce a detectable postsynaptic
      current. 3. Neurons at stage 15 showed a biphasic response to glutamate that
      reversed at the equilibrium potential for cations. All neurons tested showed a
      slow, sustained response associated with an increase in current variance compared
      with background, and, as development proceeded, an increasing proportion also
      exhibited a fast, transient response. Both fast and slow responses varied
      linearly with voltage in the absence of Mg2+ ions, but the addition of Mg2+ ions
      to the bathing medium attenuated the slow response at hyperpolarized potentials.
      As a result, the current-voltage relation of the slow response in the presence of
      Mg2+ ions exhibited a region of negative slope conductance, like that of currents
      mediated by NMDA receptors. 4. The fast and slow responses to glutamate differed
      in their pharmacological sensitivity. The fast responses were sensitive to the
      non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whereas
      the slow responses were sensitive to the NMDA receptor antagonist D(-)-2-amino-5
      phosphonovalerate (D-APV). 5. When cells were held at -70 mV, glutamate evoked a
      fluctuating current consisting of channel currents with a mean open time, tau, of
      4.42 +/- 0.47 (SE) ms in early postmitotic neurons at stage 15 and 4.99 +/- 0.38
      ms at stages 17-20.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1350795
TI  - The evolutionary origin of Plasmodium falciparum.

PMID- 1350798
TI  - Experts at Buenos Aires conference predict pandemic of tobacco deaths.

PMID- 1350796
TI  - Which anti-hypertensive to add to a beta-blocker: ACE inhibitor or diuretic?
AB  - Thirty-eight patients already treated with atenolol 50 mg once daily were
      randomly assigned to treatment with either hydrochlorothiazide (12.5-25 mg once
      daily) or lisinopril (10-20 mg once daily) for 8 weeks in a double-blind
      crossover study. Eight weeks' treatment with the combination of ACE inhibitor and
      beta-blocker or the diuretic and beta-blocker produced falls in blood pressure
      (lying: -8.4 +/- 15.4/ -7.3 +/- 80 mmHg and -6.1 +/- 15.3/ -5.2 +/- 8.8 mmHg
      [mean +/- SD] for lisinopril and hydrochlorothiazide respectively; standing: 
      10.2 +/- 14.2/8.2 +/- 9.2 mmHg and -6.8 +/- 14/ -6.3 +/- 10.3 mmHg for lisinopril
      and hydrochlorothiazide respectively) which were not statistically significantly
      different. Heart rate was significantly increased on the combination of beta
      blocker and diuretic (lying: +4.3 +/- 10.7; standing: +3.2 +/- 10.0 beats/min)
      compared with a fall on beta-blocker+ACE inhibitor (lying; -0.5 +/- 7.6;
      standing: -1.5 +/- 7.4). Both therapeutic regimens were equally well tolerated.
      These results suggest that where patients fail to respond to monotherapy with a
      beta-blocker the addition of an ACE inhibitor may be as effective as the more
      traditional option of diuretic therapy.

PMID- 1350797
TI  - Synthesis and antiallergic activity of 11-(aminoalkylidene)-6,11
      dihydrodibenz[b,e]oxepin derivatives.
AB  - A new series of 11-substituted 6,11-dihydrodibenz[b,e]oxepin-2-carboxylic acid
      derivatives was synthesized and demonstrated to be orally active antiallergic
      agents. These compounds are structurally related to 1 (KW-4994), which we had
      reported previously to be a new antiallergic agent. Most compounds synthesized
      exhibited potent inhibitory effects on 48-h homologous passive cutaneous
      anaphylaxis (PCA) in rats and on IgG1-mediated bronchoconstriction in guinea
      pigs. Additionally, compounds possessing a terminal carboxyl group at the 2
      position of the dibenz[b,e]oxepin ring system exhibited inhibitory effects on
      specific [3H]pyrilamine binding to guinea pig cerebellum histamine H1 receptors,
      whereas these demonstrated negligible effects on specific [3H]QNB binding to rat
      striatum muscarinic acetylcholine M1 receptors. Structure-activity relationship
      studies revealed that the following key elements were required for enhanced
      antiallergic activities: (1) a 3-(dimethylamino)propylidene group as the side
      chain at the 11-position, (2) a terminal carboxyl moiety at the 2-position, and
      (3) a dibenzoxepin ring system. Among the compounds synthesized, (Z)-11-[3
      (dimethylamino)propylidene]-6,11-dihydrodibenz [b,e]oxepin-2-acetic acid
      hydrochloride (16) was selected for further evaluation. It had an ED50 value of
      0.049 mg/kg po in the PCA test in rats and an ID50 value of 0.030 mg/kg po in
      inhibiting anaphylactic bronchoconstriction in guinea pigs. Furthermore, it had a
      Ki value of 16 +/- 0.35 nM for the histamine H1 receptor, while it exhibited
      negligible CNS side effects up to a dose of 600 mg/kg po. Compound 16 is now
      under clinical evaluation as KW-4679.

PMID- 1350799
TI  - World tobacco conference resolutions abound.

PMID- 1350800
TI  - H2 receptor antagonist or H. pylori eradication?
AB  - To assess the healing and relapse rate of duodenal ulcer (DU) treated with H2
      receptor antagonists in helicobacter pylori (HP) positive vs negative cases, we
      analysed 95 cases of endoscopically proven duodenal ulcer. H. pylori colonization
      was found in 73 (77%) patients before treatment. No difference was observed in
      the pre-treatment characteristics between patients with HP positive and HP
      negative duodenal ulcers. Healing rates with H2 receptor antagonist at 8 weeks
      were 90% and 91% respectively (NS). No difference in HP colonization was found
      between patients with and without healed ulcerie, 77% and 78% respectively.
      Relapse rate within 1 year was 50% in patients with HP positive vs 73% with HP
      negative cases. We conclude that duodenal ulcer healing and relapse rate is
      related to acid inhibition rather than HP colonization.

PMID- 1350801
TI  - [Clarityn--a 2-year follow-up study and comparison with Teldanex].

PMID- 1350802
TI  - [Recommendations from an expert group: drug therapy of rheumatoid arthritis].

PMID- 1350803
TI  - Morphine responsiveness of chronic pain: double-blind randomised crossover study
      with patient-controlled analgesia.
AB  - There is controversy about whether the lack of response of some chronic pain to
      opioid treatment is absolute or relative. It is widely believed that nociceptive
      pain is responsive to opioids whereas neuropathic pain tends not to be. We have
      used a method of patient-controlled analgesia (PCA) with simultaneous nurse
      observer measurement of analgesia, mood, and adverse effects to address these
      issues. Ten patients with chronic pain were given morphine at two concentrations
      (10 and 30 mg/ml) by PCA in two separate sessions in a double-blind randomised
      crossover study. Before the study a clinical judgment was made as to whether each
      pain was nociceptive or neuropathic. Seven patients showed good analgesic
      responses (more than 70 mm pain relief on a visual-analogue scale) of pain at
      rest, two patients poor responses (less than 30 mm pain relief), and one a
      moderate response with both concentrations (30-70 mm pain relief). The response
      to morphine was consistent (greater and faster relief with the higher
      concentration) in nine patients. Two patients had pain on movement that responded
      moderately to low-concentration morphine and well to the higher concentration.
      All patients with pains judged to be nociceptive showed good analgesic responses
      compared with half of those with neuropathic pain. There was no evidence that
      analgesic responses in patients with neuropathic pain were due to changes in
      mood. This PCA method is a quick and efficient tool to determine the consistency
      of the analgesic response. Such consistency can guide the clinician as to whether
      continued or higher-dose opioid treatment will produce good analgesia. An
      inconsistent response points to the use of other pain-relieving strategies.

PMID- 1350804
TI  - Use of nonoxynol-9 and reduction in rate of gonococcal and chlamydial cervical
      infections.
AB  - The spermicide nonoxynol-9 (N-9) has been used as a contraceptive for over 30
      years, but the use of a vaginal spermicide and condoms for the prevention of
      sexually transmitted infections has not been examined in randomised studies. We
      report a single-blind randomised field trial to assess the effect of N-9 film on
      the rate of gonococcal and chlamydial cervical infection in women at high risk of
      these diseases. 343 women were randomly assigned to use either condoms and N-9
      (186 women) or condoms and a placebo (157). Compliance with condom use was much
      the same in the two groups. Overall, N-9 reduced the rate of cervical infection
      by 25% (rate ratio [RR] 0.75, 95% confidence interval [Cl] 0.5-1.1); in women who
      used N-9 for more than 75% of their coital acts the infection rate was reduced by
      40% (RR 95% Cl 0.3-1.0). The rate of yeast vulvovaginitis or genital ulcers was
      not higher in N-9 users than in placebo users, but the rate of symptomatic
      irritation was increased by 70% (RR 95% Cl 1.1-2.6) among N-9 users. Condom use
      was more protective against cervical infection than N-9 use. The rate of
      infection was 50% (RR 95% Cl 0.3-0.7) lower with 75% than with 0-50% condom
      compliance. The use of a vaginal N-9 spermicide with condoms whenever possible
      seems to be a better strategy than the use of condoms only for prevention of
      gonococcal and chlamydial cervical infection.

PMID- 1350805
TI  - Debrisoquine hydroxylase gene polymorphism and susceptibility to Parkinson's
      disease.
AB  - The pathogenesis of Parkinson's disease may be influenced by genetic and
      environmental factors. Cytochrome P450 mono-oxygenases help to protect against
      toxic environmental compounds and individual variations in cytochrome P450
      expression might, therefore, influence susceptibility to environmentally linked
      diseases. The frequency of mutant CYP2D6 alleles was studied in 229 patients with
      Parkinson's disease and 720 controls. Individuals with a metabolic defect in the
      cytochrome P450 CYP2D6-debrisoquine hydroxylase gene with the poor metaboliser
      phenotype had a 2.54-fold (95% Cl 1.51-4.28) increased risk of Parkinson's
      disease. Determination of CYP2D6 phenotype and genotype may help to identify
      those at greatest risk of Parkinson's disease and may also help to identify the
      environmental or metabolic agents involved in the pathogenesis of this disease.

PMID- 1350806
TI  - Autoantibodies in pet dogs owned by patients with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) occurs in human beings and in dogs. There is
      evidence to suggest that the disease is caused by a transmissible factor that may
      cross the species barrier. We investigated this possibility by looking for
      autoantibodies and serum protein abnormalities in serum samples from 15 pet dogs
      owned by patients with SLE and comparing results with those obtained with serum
      from 10 healthy dogs kept in a controlled environment and 9 dogs with autoimmune
      diseases. We used standard immunological assays modified for use with canine
      samples. Compared with the normal dogs, increased amounts of antibody to double
      stranded DNA were found in serum from the SLE patients' dogs (median optical
      density [405 nm] = 0.117 vs 0.299; p = 0.0001), this latter amount being similar
      to that found in serum from the autoimmune group (0.201; p = 0.6). Abnormal serum
      protein electrophoresis patterns were found in samples from the autoimmune and
      SLE patients' dogs but not the normal dogs. These findings support the idea that
      exposure to common environmental factors or transmissible agents may have a role
      in causing SLE.

PMID- 1350808
TI  - Gingival sequestration of nifedipine in nifedipine-induced gingival overgrowth.
AB  - The mechanism of gingival overgrowth associated with long-term use of nifedipine
      and of other drugs that affect calcium homoeostasis, such as cyclosporin and
      phenytoin, is unknown. With an ultrasensitive assay, we measured the
      pharmacokinetics of nifedipine in plasma and gingival crevicular fluid (GCF) of
      nine patients receiving this drug for angina and hypertension. In seven patients,
      the maximum nifedipine concentration was in the range 15-316 (mean 84 [SD 105])
      times greater in GCF than in plasma. The two patients with low (undetectable) GCF
      nifedipine did not have overgrowth. We propose that gingival tissues sequester
      nifedipine and that the very high nifedipine concentrations predispose the
      tissues to overgrowth.

PMID- 1350807
TI  - Side-branch occlusion during percutaneous transluminal coronary angioplasty.
AB  - Concentrations of creatine kinase (CK) MB mass and cardiac troponin T were
      measured in serial peripheral venous blood samples from 21 patients who underwent
      percutaneous transluminal coronary angioplasty (PTCA). Angiography showed side
      branch occlusion during PTCA without clinical signs of myocardial injury in 5
      patients. After PTCA, CKMB mass concentrations were substantially higher than
      normal in all 5 patients with side-branch occlusion, and troponin T
      concentrations were high in 3. By contrast, only 2 patients and 1 patient,
      respectively, without side-branch occlusion had slight rises in CKMB and troponin
      T. Release of the contractile protein troponin T reflects more severe damage to
      myocytes than simple leakage of CKMB. Therefore, myocardial damage induced by
      side-branch occlusion can be graded by measurement of troponin T in plasma.

PMID- 1350809
TI  - Central-nervous-system dysfunction after warm or hypothermic cardiopulmonary
      bypass.
AB  - The increasing popularity of warm heart surgery led us to assess the effect of
      temperature during cardiopulmonary bypass (CPB) on neuropsychological function
      after coronary surgery. 34 patients enrolled in a randomised trial of
      normothermic versus hypothermic CPB were subjected to a battery of psychomotor
      and memory tests before and after their operations. The mean nasopharyngeal
      temperature for warm CPB was 34.7 (SD 0.5) degrees C and that for hypothermic CPB
      was 27.8 (2.0) degrees C. In all seven neuropsychological tests the postoperative
      scores were better in the warm CPB than in the hypothermic group, although only
      one difference achieved significance (trial-making test A; p less than 0.023).
      Thus, neurological function after normothermic CPB seems to be no worse than that
      after hypothermic procedures.

PMID- 1350810
TI  - Heart disease: in the beginning.

PMID- 1350811
TI  - Childhood cancer, anthracyclines, and the heart.

PMID- 1350812
TI  - Dry eyes and visual acuity.

PMID- 1350813
TI  - Cumulative conception and livebirth rates after in-vitro fertilisation.
AB  - Cumulative conception and livebirth rates related to age and cause of infertility
      provide the most useful estimate of success after in-vitro fertilisation (IVF),
      but limited data are available. It is also uncertain whether the probability of
      pregnancy, livebirth, and pregnancy failure changes with repeated treatment
      cycles. To assess the effects of patients' age and cause of infertility on these
      outcomes, we studied the results of 5055 consecutive IVF cycles (773 clinical
      pregnancies, 518 livebirths) undertaken on 2735 patients in a single IVF unit.
      Cumulative conception and livebirth rates were analysed by the life-table
      approach and differences in rates between age-groups and between causes of
      infertility were measured by the log-rank test and logistic regression modelling.
      Both conception and livebirth rates per cycle declined with age (p less than
      0.001), and cumulative conception and livebirth rates after five treatment cycles
      were about 54% and 45%, respectively, at 20-34 years, compared with 38.7% and
      28.9% at 35-39 years and 20.2% and 14.4% at greater than or equal to 40 years.
      The two rates were significantly different between causal groups (p less than
      0.001 and p = 0.02, respectively) and were lowest in patients with male
      infertility or multiple infertility factors. The pregnancy failure rate was
      higher (p = 0.006) in women over the age of 34 years and there was a significant
      decline in the chances of pregnancy and livebirth per cycle with successive
      treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350815
TI  - Lamotrigine.

PMID- 1350814
TI  - Critical study of consensus analysis.
AB  - Consensus analysis has been proposed as a statistical method by which the
      efficacy of clinical and laboratory tests of inflammatory activity can be
      assessed. This technique is claimed to overcome the need for an external "gold
      standard" as a reference method; instead, the consensus of all tests is used as
      the gold standard. We have evaluated the reliability of consensus analysis using
      data collected from patients with Crohn's disease. Our results demonstrate that
      the technique depends strongly on the correlation structure underlying the set of
      measures of disease used for analysis. This observation was supported by a series
      of conventional cluster analyses of the same set of variables. Furthermore,
      slight modifications of the algorithm had profound effects on the final result.
      We conclude that for the evaluation of tests of inflammatory activity, an
      external reference method, albeit an imperfect one, remains indispensable.

PMID- 1350816
TI  - GP maternity units.

PMID- 1350817
TI  - Selective decontamination of the digestive tract and methicillin-resistant
      Staphylococcus aureus.

PMID- 1350818
TI  - Expression of thrombospondin-related anonymous protein in Plasmodium falciparum
      sporozoites.

PMID- 1350819
TI  - Arsenic, selenium, and African trypanosomiasis.

PMID- 1350820
TI  - Aflatoxin biomarkers.

PMID- 1350821
TI  - Peripheral intravenous nutrition.

PMID- 1350822
TI  - Endotoxin antibody for sepsis in infants.

PMID- 1350823
TI  - Endotoxin antibody for sepsis in infants.

PMID- 1350824
TI  - Laboratory diagnosis of brucella infection: some pitfalls.

PMID- 1350825
TI  - Early confirmation of trisomy 18 in newborn babies.

PMID- 1350826
TI  - Congenital abnormalities (VATER) in baby born to mother using lovastatin.

PMID- 1350827
TI  - Effects of thyrotropin-releasing hormone on fetal heart rate.

PMID- 1350828
TI  - Improvement of patient with amyotrophic lateral sclerosis given ceftriaxone.

PMID- 1350829
TI  - AIDS and the Murdoch press.

PMID- 1350830
TI  - Coronary care for elderly patients.

PMID- 1350831
TI  - Bias due to measurement imprecision.

PMID- 1350832
TI  - European Boards and Colleges.

PMID- 1350833
TI  - Ductal carcinoma-in-situ of the breast.

PMID- 1350834
TI  - Reaction time and transcranial magnetic stimulation.

PMID- 1350835
TI  - Neurological symptoms and coma associated with doxorubicin administration during
      chronic cyclosporin therapy.

PMID- 1350836
TI  - Ciprofloxacin to prevent catheter-associated urinary tract infection.

PMID- 1350837
TI  - Ciprofloxacin to prevent catheter-associated urinary tract infection.

PMID- 1350838
TI  - Loss of heterozygosity, chromosome 7q, and breast cancer.

PMID- 1350839
TI  - Laser micromanipulation of oocytes and sperm.

PMID- 1350840
TI  - Hospital outbreak of hepatitis E.

PMID- 1350841
TI  - HCV and PCR negativity.

PMID- 1350842
TI  - HCV and Sjogren's syndrome.

PMID- 1350843
TI  - Cholesterol in elderly women.

PMID- 1350844
TI  - False-positive immunoassay for Chlamydia in urine.

PMID- 1350845
TI  - Origins of HIV.

PMID- 1350846
TI  - Prevalence of Leishmania infection among AIDS patients.

PMID- 1350847
TI  - Cardiac arrhythmia and Leber's hereditary optic neuropathy.

PMID- 1350848
TI  - Octreotide.

PMID- 1350849
TI  - Successful pregnancy in severe diabetes.

PMID- 1350850
TI  - Effects of the alpha 1-adrenergic agonist cirazoline on locomotion and brown
      adipose tissue thermogenesis in the rat.
AB  - Anorexia is induced by injection of alpha 1-adrenergic receptor agonists into the
      hypothalamic paraventricular nucleus (PVN) in rats. Of the agonists tested to
      date, cirazoline is the most potent when administered either into the PVN or
      systemically. The present experiments assess the effects of systemically
      administered cirazoline, at doses that suppress food intake, on dopamine and
      norepinephrine systems as evident in locomotion and stereotypy and in the
      induction of brown adipose tissue (BAT) thermogenesis. In Experiment 1, adult
      male rats were treated with either vehicle (0) or 0.05, 0.1, 0.2 or 0.4 mg/kg
      cirazoline (IP) prior to 30 minutes assessment of horizontal and vertical
      locomotion and stereotypy in Omnitech activity chambers. Horizontal activity and
      stereotypy were significantly suppressed at 0.05 mg/kg cirazoline but these
      effects waned at higher cirazoline doses. In Experiment 2, interscapular BAT
      temperature in adult male rats was monitored for 30 minutes after injection (IP)
      of either vehicle or 0.4 mg/kg cirazoline. Cirazoline, at 0.4 mg/kg did not
      influence BAT temperature whereas a positive control treatment
      (phenylpropanolamine: 40 mg/kg) rapidly increased BAT temperature during a 15
      minute period after injection. These results suggest that cirazoline-induced
      anorexia is not the result of competing motor responses and that this drug, at a
      dose that produces maximal suppression of feeding, does not alter BAT
      thermogenesis.

PMID- 1350852
TI  - A decade of the AIDS epidemic, report on the Seventh International Conference on
      AIDS, Florence, Italy, 16-21 June 1991.

PMID- 1350851
TI  - Subchronic treatment with metformin produces anorectic effect and reduces
      hyperinsulinemia in genetically obese Zucker rats.
AB  - The effect of subchronic metformin treatment on food intake, weight gain and
      plasma and tissue hormone levels was investigated in genetically obese male
      Zucker rats and in their lean controls. Metformin hydrochloride (320 mg/kg/day
      for 14 days in the drinking water) significantly reduced 24 hour food intake both
      after one and two weeks treatment in obese rats. In contrast, metformin had only
      a transient effect on food intake in lean animals. The reduced food intake was
      associated with body weight decrease, particularly in obese rats. Metformin
      markedly reduced also the hyperinsulinemia of the obese animals without altering
      their plasma glucose or pancreatic insulin content which may reflect an improved
      insulin sensitivity after metformin treatment. Metformin did not change plasma
      corticosterone levels or insulin and somatostatin concentrations in the pancreas.
      Metformin reduced pyloric region somatostatin content in lean rats. It is
      concluded that metformin has an anorectic effect and reduces body weight and
      hyperinsulinemia in genetically obese Zucker rat.

PMID- 1350853
TI  - Prenatal diagnosis of Wilson's disease by analysis of DNA polymorphism.

PMID- 1350855
TI  - Italian Society of Physiology XVIII Spring Meeting. Firenze, Italy, 4-6 April
      1991. Abstracts.

PMID- 1350854
TI  - [Effect of trans-ACPD, a specific agonist of glutamate interacting with
      metabotropic receptors, on synaptic transmission in the rat hippocampus].
AB  - Trans-ACPD, a cyclic analogue of glutamate, has been studied for its influence on
      field potentials and excitatory postsynaptic currents (EPSCs) in the CA1 layer.
      Being applied in concentration 50 microM and above, trans-ACPD completely and
      reversibly inhibited excitatory postsynaptic field potentials but has no effect
      on EPSCs. Trans-ACPD in the same concentration reversibly reduced the amplitude
      of antidromic population spike in the CA1 layer, but has an insignificant effect
      on antidromic population spike in the CA3 layer.

PMID- 1350856
TI  - Italian Society of Physiology XLIII Annual General Congress. Sorrento, Italy, 23
      26 September 1991. Abstracts.

PMID- 1350857
TI  - The bromodomain: a conserved sequence found in human, Drosophila and yeast
      proteins.

PMID- 1350858
TI  - 3rd Joint Meeting of Hungarian, Italian and Polish Pharmacological Societies.
      Modern (Italy), June 8-10, 1992. Proceedings.

PMID- 1350859
TI  - Management of acute MI.

PMID- 1350860
TI  - New drugs for peptic ulcers.

PMID- 1350861
TI  - [Hazards of treatment of psoriasis with sulfasalozine].

PMID- 1350863
TI  - [Swiss Society of Cardiology, Swiss Society of Aeronautic Medicine, annual
      meeting and Swiss Society of Hematology, annual meeting. Geneva, June 11-13,
      1992. Abstracts].

PMID- 1350862
TI  - [DNA markers linked to Huntington's disease (D4S10 and D4S95) in Spanish
      families: preliminary results].
AB  - We have studied six Spanish families with at least one affected member with
      Huntington's disease, using RFLPs from probes linked to the gene. Our results
      suggest a genetic homogeneity in our population and show a 100% of informativity
      with the probes and enzymes used.

PMID- 1350864
TI  - A first in cell transplantation: researchers organize, meet.

PMID- 1350865
TI  - Early stages of motor neuron differentiation revealed by expression of homeobox
      gene Islet-1.
AB  - Motor neurons in the embryonic chick spinal cord express a homeobox gene, Islet
      1, soon after their final mitotic division and before the appearance of other
      differentiated motor neuron properties. The expression of Islet-1 by neural cells
      is regulated by inductive signals from the floor plate and notochord. These
      results establish Islet-1 as the earliest marker of developing motor neurons. The
      molecular nature of the Islet-1 protein suggests that it may be involved in the
      establishment of motor neuron fate.

PMID- 1350866
TI  - [Effects of thyroxine and methimazolum on monamine transmitters in
      preoptic/anterior hypothalamic area and peripheral serum in rats].
AB  - The contents of monamine transmitters in preoptic/anterior hypothalamic (PO/AH)
      area and in the serum of rats injected with thyroxine (T4, 1 mg/100 g body wt/d,
      for 10 d, hypodermic i.) and fed with methimazolum (10 mg/100 g body wt/d, for 15
      d) were assayed by high pressure liquid chromatography with electrochemical
      detector (HPLC-ECD). It was found that the content of dopamine and homovanillic
      acid in PO/AH area showed significant increase (P less than 0.01) associated with
      a slight rise (P greater than 0.05) of 5-hydroxytryptamine (5-HT) and 5
      hydroxyindoleacetic acid (5-HIAA), and with no change of norepinephrine in the
      thyroxine group. After fed with methimazolum, the content of norepinephrine
      decreased significantly (P less than 0.05), but no obvious changes occurred in
      dopamine, homovanillic acid, 5-HT and 5-HIAA. By synchronous analysing of
      monamine transmitters in peripheral serum, it was showed that there was no
      significant linear relationship between the changes of monamine transmitters in
      the brain and in the serum. The correlation between thyroxine and methimazolum on
      the content of monamine transmitters and on the change of body temperature was
      also discussed.

PMID- 1350867
TI  - Calcitonin immunoreactivity and hypercalcitoninemia in two patients with
      sporadic, nonfamilial, gastroenteropancreatic neuroendocrine tumors.
AB  - BACKGROUND: Hypercalcitoninemia in gastroenteropancreatic tumors associated with
      calcitonin immunoreactivity is rare. METHODS: We report here two patients in whom
      pancreatic neuroendocrine tumors both contained and secreted immunoreactive
      calcitonin. Both patients experienced elevated basal calcitonin immunoreactivity.
      RESULTS: The peak responses of immunoreactive calcitonin occurred 5 minutes after
      pentagastrin administration in these two patients and were 30% and 180% above
      basal concentrations corresponding to peak increments of 0.39 and 8.78 ng/ml,
      respectively. The immunoreactive calcitonin response to pentagastrin in these two
      patients was not significantly different from that seen among five patients with
      medullary carcinoma of the thyroid gland. CONCLUSION: It does not appear that
      immunoreactive calcitonin responses to pentagastrin stimulation will discriminate
      between patients with medullary carcinoma of the thyroid gland and those with
      nonfamilial, gastroenteropancreatic neuroendocrine tumors that express calcitonin
      immunoreactivity. In patients with secretory diarrhea and/or flushing, an
      elevated level of immunoreactive calcitonin, in the absence of a thyroid mass in
      the neck, may herald the presence of a gastroenteropancreatic neuroendocrine
      tumor.

PMID- 1350868
TI  - Hormonal and neural blockade prevents the postoperative increase in amino acid
      clearance and urea synthesis.
AB  - The combined effect of continuous blockade of glucagon and cortisol by
      somatostatin and etomidate and thoracic epidural analgesia on hepatic conversion
      of amino nitrogen was studied in eight patients who underwent elective
      cholecystectomy on day 1 after operation and was compared with 16 patients who
      underwent operation without blockade. Surgery increased the plasma clearance of
      total alpha-amino nitrogen from 5.2 +/- 0.3 to 6.6 +/- 0.3 ml/sec (mean +/- sem;
      p less than 0.05). This increase was due to increased elimination by the liver,
      because the hepatic effectiveness for amino nitrogen conversion measured by the
      functional hepatic nitrogen clearance increased from 9 +/- 2 to 16 +/- 4 ml/sec
      (p less than 0.05). In contrast, during the combined neural and hormonal
      blockade, surgery decreased the plasma clearance of amino nitrogen from 5.3 +/-
      0.3 to 3.9 +/- 0.3 ml/sec (p less than 0.05), and the blockade prevented the
      postoperative increase in functional hepatic nitrogen clearance. The results
      suggest that glucagon, cortisol, and afferent neural reflexes are mediators of
      the hepatic contribution to catabolism after operation.

PMID- 1350869
TI  - HLA-DP antigen and Takayasu arteritis.
AB  - Sixty-four patients with Takayasu arteritis and 317 healthy individuals in the
      Japanese population were examined for HLA-A, -B and -C alleles by serological
      typing and for HLA-DR, DQ and DP alleles by DNA typing using PCR/SSOP analysis.
      The frequencies of HLA-Bw52, DRB1*1502, DRB5*0102, DQA1*0103, DQB1*0601 and
      DPB1*0901 alleles were significantly increased and the frequencies of HLA-Bw54,
      DRB1*0405, DRB4*0101, DQA1*0301, DQB1*0401 alleles were significantly decreased.
      Strong linkage disequilibria among the increased alleles and among the decreased
      alleles were evident in the Japanese population. Therefore, the combination or
      haplotype of HLA-Bw52-DRB1*1502-DRB5*0102-DQA1*0103-DQB1*0601 -DPA1*02-DPB1*0901
      may confer susceptibility to Takayasu arteritis while another combination or
      haplotype of HLA-Bw54-DRB1*0405-DRB4*0101-DQA1*0301-DQB1++ +*0401 may confer
      resistance to the disease. Because this is the first evidence for the association
      between an HLA-DP allele and Takayasu arteritis, we examined the nucleotide
      sequences of the DPB1*0901 allele from a patient and her healthy relatives and
      found no difference. The disease is therefore not caused by a mutated DPB1 gene.

PMID- 1350870
TI  - Sequence differences between HLA-B and TNF distinguish different MHC ancestral
      haplotypes.
AB  - The HLA-B locus is extremely polymorphic. We have sequenced a region, CL,
      telomeric of HLA-B that also shows a high degree of allelic variation which we
      have shown previously by RFLP analysis. The polymorphism can be accounted for by
      sequence variation in duplicated, reiterated sequence elements called geometric
      elements. Comparison of the CL1 and CL2 sequences from the 57.1, 8.1, 18.2 and
      7.1 ancestral haplotypes revealed that the lengths of the elements vary, both
      between the duplicated loci within a haplotype and between haplotypes, apparently
      because certain sequences are inserted or deleted. It is possible, using the
      polymerase chain reaction, to amplify these elements in genomic DNA from
      ancestral haplotypes for which sequence data of the CL region are not available
      and to obtain gel patterns which are characteristic of different ancestral
      haplotypes. The most striking feature of the data is the fact that the majority
      of the CL patterns are haplospecific; i.e. have a particular pattern that is
      unique for a particular ancestral haplotype and can be used to type these
      ancestral haplotypes. At least 12 different allelic patterns have been identified
      within a panel of 29 cell lines representing 16 ancestral haplotypes. For these
      16 ancestral haplotypes, all examples of each haplotype have the same CL pattern.
      The haplotypic nature of the patterns confirms that ancestral haplotypes are
      conserved chromosomal segments and that coding and non-coding sequences are
      identical by descent from a remote ancestor.

PMID- 1350871
TI  - Studies of the HLA class II alleles involved in human responses to ragweed
      allergens Ambrosia artemisiifolia V (Ra5S) and Ambrosia trifida V (Ra5G)
AB  - Previous studies have associated skin test sensitivity and specific IgE response
      to Ambrosia artemisiifolia V (Amb a V) with HLA-DR2, and to Ambrosia trifida V
      (Amb t V) with HLA-DRw52 haplotypes in atopic individuals. Using HLA class II
      typing by restriction fragment length polymorphism (RFLP) analysis with DRB, DQB
      and DQA DNA probes to define the HLA-D alleles, we have demonstrated the
      association of the DQw6 in 16 out of 16 (100%) Amb a V-responsive individuals,
      compared to 3 out of 18 (17%) ragweed-sensitive but Amb a V-nonresponsive
      individuals (p = 5.7 x 10(-6), RR greater than 75). We suggest that the DQw6
      association with Amb a V sensitivity may be a reflection of an association with
      the DQA*0102 allele. This suggests an association of a particular HLA class II
      allele with an immune response to a well-characterized antigen (Amb a V). The HLA
      DRw52 haplotypes in the Amb t V-sensitive individuals are not of one particular
      subtype. The HLA-DRw52 association with Amb t V sensitivity may reside in
      homologous DRB1 alleles linked on HLA-DRw52-bearing haplotypes.

PMID- 1350873
TI  - Patient Controlled Analgesia. International Symposium on PCA. Genval, May 9,
      1992.

PMID- 1350872
TI  - The serological definition of HLA-DRBr using 11th workshop reagents.

PMID- 1350874
TI  - The acute pain service.

PMID- 1350875
TI  - Intravenous PCA and postoperative balanced analgesia.

PMID- 1350876
TI  - Pharmacokinetics and patient-controlled analgesia.
AB  - With patient control over dosage regimens as in PCA, the pharmacodynamic
      properties of the opioid analgesic agents emerge as being of greater importance
      than the pharmacokinetic properties in obtaining a salutary result. However, the
      prescription of opioid analgesic agents for PCA is more complex than for the same
      drugs under conventional control. There are major differences in the
      physicochemical, receptor selectivity and pharmacokinetic properties among opioid
      analgesic agents. Improved understanding of these differences, it is contended,
      can lead to more optimized strategies for the clinical management of pain whether
      under conventional or patient control. The impact of these properties on the
      components of the PCA prescription is discussed.

PMID- 1350877
TI  - Patient-controlled analgesia in children.
AB  - The use of patient-controlled analgesia in children and adolescents undergoing
      major surgery is safe and effective provided that patients are carefully
      selected, adequate information is provided to patients, adequate training is
      given to hospital staff and efficacy as well as side-effects are appropriately
      monitored. Practical guidelines and examples of complications are given.

PMID- 1350879
TI  - Safety aspects of PCA.

PMID- 1350878
TI  - Epidural patient controlled analgesia with bupivacaine and sufentanil.

PMID- 1350880
TI  - [Effects of alpha adrenoceptor agonists and antagonists on palpebral fissure and
      lacrimation in mice].
AB  - Ip methoxamine (Met), norepinephrine (NE), xylazine (Xyl), and clonidine (Clo)
      produced dose-related reversal of ptosis induced by reserpine. These agonists had
      equivalent Emax values, however, the order of potency was: Clo greater than Met
      approximately NE greater than Xyl. Met-induced antiptotic action was
      competitively inhibited by prazosin (Pra) (apparent pA2 = 6.86), but not by
      idazoxan (Ida); Xyl-induced antiptotic action was competitively inhibited by Ida
      (apparent pA2 = 6.39), but inhibited by Pra in a noncompetitive manner. These
      results suggested that the eyelids of mice had both alpha-1 and alpha-2
      adrenoceptors. In mice lacrimal gland, Met, and NE elicited dose-related lacrimal
      secretions, however, Xyl and Clo had no such reaction. Lacrimal secretions
      elicited by Met or NE were inhibited by Pra, but not by Ida. These results
      suggested that the lacrimal gland of mice had only alpha-1 adrenoceptor.

PMID- 1350881
TI  - [Central analgesic action of calcitonin and its relationship with central
      monoamine transmitters].
AB  - The analgesic action of calcitonin (0.25 MRC units.kg-1) injected into lateral
      cerebral ventricle was investigated in rats. The pain threshold was evaluated by
      the tail-flick test. The influences of icv naloxone 5 micrograms/rat, a blocker
      of opiate receptor, on the analgesic action of calcitonin were observed. The
      results showed that icv calcitonin produced a significant analgesic action, which
      was reversed by naloxone. While the pain threshold was raised by calcitonin, the
      contents of central monoamines (5-HT, NE, DA) in brain (diencephalon, brain stem)
      were examined by fluorophotometry, which were increased remarkably. It is
      suggested that calcitonin-induced analgesia is related to the opiate receptors
      and the contents of 5-HT, NE, and DA in CNS.

PMID- 1350882
TI  - Acute and long-term effects on myocardial ischemia of intermittent and continuous
      transdermal nitrate therapy in stable angina.
AB  - The aim of this study was to compare the efficacy and safety of continuous and
      intermittent transdermal nitrate therapy using ambulatory electrocardiographic
      (Holter) monitoring. Eighty-five patients with stable angina pectoris and
      positive exercise test results participated during their concomitant antiischemic
      medication in a randomized open trial lasting 12 weeks. After a 3-week run-in
      period with continuous therapy (10 mg/24 hours), patients were randomized to
      either continuous- or intermittent-therapy groups. In the intermittent-therapy
      group the patients removed their patch at night (the mean patch-off period was 10
      hours). Forty-eight-hour Holter monitoring was performed in each patient after
      randomization, and again after 2 and 12 weeks. Eighteen patients withdrew, 9 in
      each group. A total of 11,194 hours of electrocardiography were recorded and 607
      ischemic episodes were detected, of which 79% were asymptomatic and 95% appeared
      during daytime. The number of ischemic episodes per 48 hours with intermittent
      therapy was 3.1 +/- 0.7 (mean +/- SEM) after randomization, 1.8 +/- 0.4 at 2
      weeks and 2.0 +/- 0.6 at 12 weeks. With continuous therapy the respective numbers
      were 3.8 +/- 1.1, 3.5 +/- 0.9 and 4.2 +/- 1.2. The differences were not
      statistically significant because a large number of patients (30%) had no
      ischemic episodes on Holter recording. However, when examining 47 patients with
      episodes during the study, the number of episodes was significantly reduced in
      the intermittent-therapy group (p less than 0.05 at 12 weeks). The changes in
      asymptomatic and symptomatic episodes were concordant. No changes and differences
      between the treatment groups were seen in nighttime episodes.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1350883
TI  - Composition and in vitro corrosion of orthodontic appliances.
AB  - The high incidence of nickel allergy and the increasing use of nickel-containing
      dental biomaterials has been of growing concern. The purpose of this
      investigation was to analyze different types of alloys used in orthodontics, and
      to study whether nickel and chromium will be released from these alloys when
      stored in physiologic saline. Face-bows, brackets, molar bands, and arch wires
      were analyzed. Most of the different parts in the face-bows, brackets, and molar
      bands were similar to conventional 18/8 stainless steel. Except the wires, most
      appliances included a variable amount of silver solder, the greatest in face
      bows. After 14 days in 0.9% sodium chloride (NaCl), the largest amount of nickel
      and chromium were leached out from the face-bows and the least amount from the
      arch wires. Soldered stainless steel face-bows seemed to be very susceptible to
      corrosion. The release of nickel seemed to be related to both the composition and
      the method of manufacture of the appliances, but the release was not proportional
      to the nickel content.

PMID- 1350885
TI  - Correction of sulfatide metabolism after transfer of prosaposin cDNA to cultured
      cells from a patient with SAP-1 deficiency.
AB  - The lysosomal removal of the sulfate moiety from sulfatide requires the action of
      two proteins, arylsulfatase A and sphingolipid activator protein-1 (SAP-1).
      Recently, patients have been identified who have a variant form of metachromatic
      leukodystrophy which is characterized by mutations in the gene coding for SAP-1,
      which is also called "prosaposin." All of the mutations characterized in these
      patients result in (a) deficient mature SAP-1, as determined by immunoblotting
      after SDS-PAGE of tissue and cell extracts, and (b) decreased ability of cultured
      skin fibroblasts to metabolize endocytosed [14C]-sulfatide. We now report the
      insertion of the full-length prosaposin cDNA into the Moloney murine leukemia
      virus-derived retroviral vector, pLJ, and the infection of cultured skin
      fibroblasts from a newly diagnosed and molecularly characterized patient with SAP
      1 deficiency. The cultured cells infected with the prosaposin cDNA construct now
      show both production of normal levels of mature SAP-1 and completely normal
      metabolism of endocytosed [14C]-sulfatide. These studies demonstrate that the
      virally transferred prosaposin cDNA is processed normally and is localized within
      lysosomes, where it is needed for interaction between sulfatide and arylsulfatase
      A. In addition, normal as well as mutant sequences can now be found by allele
      specific oligonucleotide hybridization of PCR-amplified genomic DNA by using
      exonic sequences as primers.

PMID- 1350884
TI  - Recombination of 4p16 DNA markers in an unusual family with Huntington disease.
AB  - The Huntington disease (HD) mutation has been localized to human chromosome 4p16,
      in a 6-Mb region between the D4S10 locus and the 4p telomere. In a report by
      Robbins et al., a family was identified in which an affected individual failed to
      inherit three alleles within the 6-Mb region originating from the parental HD
      chromosome. To explain these results, it was suggested that the HD locus (HD)
      lies close to the telomere and that a recombination event took place between HD
      and the most telomeric marker examined, D4S90. As a test of this telomere
      hypothesis, we examined six members of this family, five of whom are affected
      with HD, for the segregation of 12 polymorphic markers from 4p16, including
      D4S169, which lies within 80 kb of the 4p telomere. We separated, in somatic cell
      hybrids, the chromosomes 4 from each family member, to determine the phase of
      marker alleles on each chromosome. We excluded nonpaternity by performing DNA
      fingerprint analyses on all six family members, and we found no evidence for
      chromosomal rearrangements when we used high-resolution karyotype analysis. We
      found that two affected siblings, including one of the patients originally
      described by Robbins et al., inherited alleles from the non-HD chromosome 4 of
      their affected parents, throughout the 6-Mb region. We found that a third
      affected sibling, also studied by Robbins et al., inherited alleles from the HD
      chromosome 4 of the affected parent, throughout the 6-Mb region. Finally, we
      found that a fourth sibling, who is likely affected with HD, has both a
      recombination event within the 6-Mb region and an additional recombination event
      in a more centromeric region of the short arm of chromosome 4. Our results argue
      against a telomeric location for HD and suggest that the HD mutation in this
      family is either associated with DNA predisposed to double recombination and/or
      gene conversion within the 6-Mb region or is in a gene that is outside this
      region and that is different from that mutated in most other families with HD.

PMID- 1350886
TI  - Limiting subsequent mutagenic events in carriers of hereditary tumor genes.

PMID- 1350887
TI  - Synergistic interaction between alpha 2-adrenergic agonists and benzodiazepines
      in rats.
AB  - Both alpha 2-adrenergic agonists and benzodiazepines exert anxiolytic and
      sedative effects when administered as preoperative medications. Clinical effects
      achieved with a combination of drugs, representative of these classes of
      compounds, is greater than that which could be expected from a simple additive
      response. Therefore, we investigated the nature of the interaction between
      dexmedetomidine, the highly-selective alpha 2-adrenergic agonist, and midazolam
      in a series of in vivo and in vitro studies in rats. Rats were administered
      midazolam, dexmedetomidine, or a combination of midazolam and dexmedetomidine
      intravenously to derive three dose-response curves for loss of righting reflex
      (LRR). LRR was determined in rats in a rotating cage (4 rotations/min) by
      observing whether the rat failed to maintain its upright posture for greater than
      or equal to 15 s exactly 2.5 min after drug administration. The effect of either
      flumazenil (benzodiazepine receptor antagonist) or atipamezole (the alpha 2
      adrenergic antagonist) on the LRR was also determined. A probit analysis was
      performed and an isobologram for the ED50 was derived to assess the nature of the
      interaction. Rat brain membranes were prepared for receptor binding assays using
      [3H]-flumazenil and [3H]-rauwolscine to characterize the benzodiazepine and alpha
      2-adrenergic receptors, respectively. The ability of either midazolam or
      dexmedetomidine to displace the radiolabeled ligand from the alternative receptor
      was assessed. To detect a possible kinetic interaction between the two drugs,
      separate cohorts of rats were administered the two drugs individually or in
      combination at the combination ED50 doses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350888
TI  - The locus coeruleus. Site of hypnotic actions of alpha 2-adrenoceptor agonists?

PMID- 1350889
TI  - A hypnotic response to dexmedetomidine, an alpha 2 agonist, is mediated in the
      locus coeruleus in rats.
AB  - Dexmedetomidine, the highly selective alpha 2-adrenergic agonist, produces a dose
      dependent hypnotic response in rats through a central mechanism. Because the
      locus coeruleus (LC) contains pathways involved in the maintenance of vigilance
      and a high prevalence of alpha 2 adrenoceptors, we investigated the role of this
      brainstem nucleus in the hypnotic response to dexmedetomidine. The experimental
      model consisted of chronic, stereotactically cannulated rats (n = 157) in which
      the hypnotic response to dexmedetomidine was assessed by the duration of the loss
      of their righting reflex. Correct placement of the cannula was confirmed
      histologically at necropsy. The hypnotic response to dexmedetomidine 0.3-333.3
      micrograms administered into the LC increased in a dose-dependent fashion.
      Dexmedetomidine 6.6 micrograms injected 2 mm lateral to the LC did not cause the
      animals to lose their righting response. Atipamezole 0.07 micrograms-12
      micrograms, a selective alpha 2-adrenergic antagonist, blocked the hypnotic
      response to dexmedetomidine 6.6 micrograms when both were administered into the
      LC. Also, atipamezole 0.7-30 micrograms, administered into the LC, blocked in a
      dose-dependent manner the hypnotic response to intraperitoneal (ip)
      dexmedetomidine 50 micrograms.kg-1. Atipamezole injected into the LC did not
      block the hypnotic response to pentobarbital 40 mg.kg-1 ip. Prazosin, an alpha 1
      adrenergic antagonist, 4.2 micrograms into the LC or 1.0 mg.kg-1 ip, did not
      alter the hypnotic response to dexmedetomidine 6.6 micrograms into the LC. The
      present data suggest that alpha 2-adrenergic receptors in the LC appear to be a
      major site for the hypnotic action of dexmedetomidine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1350890
TI  - Developmental toxicity of nondepolarizing muscle relaxants in cultured rat
      embryos.
AB  - Evidence of developmental toxicity of clinically used nondepolarizing muscle
      relaxants was sought in rat embryos grown in culture. Embryos were explanted at 8
      AM on day 9 of gestation (presomite stage, plug day = day 0), and were cultured
      in rotating bottles with medium containing various concentrations of d
      tubocurarine, pancuronium, atracurium, and vecuronium. At 10 AM on day 11 of
      gestation (forelimb bud stage), culture was terminated and embryos were examined
      for general morphology. Treatment with tested agents resulted in dose-dependent
      developmental toxicity; namely, growth retardation seen as decreased crown-rump
      length, decreased number of somite pairs, and morphologic abnormalities. However,
      the concentrations that caused toxicity were at least 30-fold greater than serum
      concentrations clinically achieved in the mother. We conclude that these muscle
      relaxants have a low potential for causing developmental toxicity during
      organogenesis.

PMID- 1350891
TI  - Peripheral vestibular transmission.

PMID- 1350892
TI  - Neurotransmitters in the vestibular commissural system of the cat.
AB  - The present study focused on the transmitters that control the vestibular neural
      activity and, in particular, that regulate commissural inhibition. Extracellular
      spikes of a single vestibular neuron were recorded in decerebrate cats. The seven
      barrels of the electrode, with the exception of the center barrel, were filled
      with transmitter candidates and their specific antagonists, while the center
      barrel was filled with 2 M NaCl for extracellular recording. After isolation of a
      type 1 neuron, chemicals were iontophoretically applied to examine their effects
      on its activity. The results were as follows: (1) GABA and glycine markedly
      decreased spontaneous firing of the neurons, while serotonin did not affect their
      activity. (2) Bicuculline abolished the inhibitory effects of GABA on the
      neurons. (3) Strychine abolished the effects of glycine. (4) Commissural
      inhibition induced by electrical stimulation of the contralateral labyrinth was
      not abolished by strychine but was abolished by bicuculline. We conclude that (1)
      vestibular type 1 neurons are controlled by GABAergic and glycinergic but not
      serotoninergic neurons, and (2) commissural inhibition is activated by the GABAA
      receptor, but not by the GABAB receptor.

PMID- 1350893
TI  - GABA and glycine as inhibitory neurotransmitters in the vestibuloocular reflex.

PMID- 1350894
TI  - Modulation of excitatory transmission at the rat medial vestibular nucleus
      synapse.

PMID- 1350895
TI  - Neurotransmitter and peptide receptors on medial vestibular nucleus neurons.

PMID- 1350896
TI  - Computer-assisted three-dimensional reconstruction and simulations of vestibular
      macular neural connectivities.
AB  - The macular neuroepithelium is morphologically organized as a weighted neural
      network for parallel distributed processing of information. The network is
      continuous across the striola, where some type II hair cells synapse with calyces
      containing type I cells with tufts of opposite directional polarities. Whether
      other hair cell to calyx appositions that lack synapses interact because of
      intercellular potassium accumulation remains an open question. A functionally
      important inference of macular organization is that just as arrays of hair cells
      communicate an entire piece of information to a nerve fiber, so do macular
      subarrays of nerve fibers (not single units) carry the whole coded message to the
      brain stem. Moreover, the size of the network subarray can expand or become more
      limited depending upon the strength and/or duration of the input. It is the
      functioning of the network and its subarrays that must be understood if we are to
      learn how maculas carry out their work and adapt to new environments. Simulations
      of functioning maculas, or subparts, based on precise morphology and known
      physiology are useful tools to gain insights into macular information processing.
      The current simulations of afferent collateral electrical activity are a prelude
      to development of a 3-D model. The simulations demonstrate a relationship between
      geometry and function, with the diameter of the stem apparently being a major
      determinant of electrical activity transmitted to the base in the case of
      collaterals with short stems. Thus, while changes in synaptic number and/or size
      may be an important adaptive mechanism in an altered g environment, changes in
      diameter of the stem is another means of altering outflow. Research on the
      effects of microgravity should be extremely useful in examining the validity of
      this and other concepts of neural adaptation, since maculas are biological linear
      accelerometers ideally suited to the task. Maculas are also extremely interesting
      to study in detail because of the richness of connectivities and submicroscopic
      organization they present. Many of their features are common with more complex
      parts of the brain. It seems possible that knowledge of the three-dimensional
      geometric relationships operative in a functioning macula will contribute much to
      the understanding of the dynamics underlying more complex behavior. Computerized
      approaches greatly facilitate this task and provide an objective method of
      analysis. It is likely that, in the end, simple rules will be found to govern
      optimal neural architectural organization, even at higher cognitive levels. The
      architecture only appears complex because we do not yet grasp its
      meaning.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1350898
TI  - The natural course of multiple endocrine neoplasia type IIb. A study of 18 cases.
AB  - BACKGROUND: Multiple endocrine neoplasia (MEN) type IIb is an autosomal
      dominantly inherited disorder associated with medullary thyroid cancer,
      pheochromocytoma, and a characteristic phenotype. The present study was performed
      to investigate the natural course of the syndrome and to describe its expression.
      METHODS: The medical records of 18 patients with MEN IIb, seven male and 11
      female, were reviewed. RESULTS: The mean age at diagnosis of MEN IIb was 18 years
      (range, 8 to 41 years). All 18 patients had medullary thyroid cancer. In three
      patients, medullary thyroid cancer was diagnosed via screening. In two of these
      patients, the calcitonin value normalized after thyroidectomy. One patient died
      of metastases from medullary thyroid cancer at the age of 20 years (median
      duration of follow-up, 10 years). Eight of the 18 patients had pheochromocytomas.
      All of our patients had neuromas and bumpy lips, and all but one had a marfanoid
      habitus. A large proportion of the patients had intestinal abnormalities (75%),
      thickened corneal nerves (69%), skeletal abnormalities (87%), and delayed puberty
      (43%). CONCLUSIONS: The course of medullary thyroid cancer in MEN IIb is not
      always as aggressive as is generally thought. Periodic examination of relatives
      who are at risk may lead to early diagnosis and curative treatment. Intestinal
      abnormalities, skeletal abnormalities, and delayed puberty are commonly found in
      association with MEN IIb.

PMID- 1350897
TI  - Cytotoxic effects of somatostatin in the cerebellum.

PMID- 1350899
TI  - Acute syphilitic meningitis in a man with seropositivity for human
      immunodeficiency virus infection and normal numbers of CD4 T lymphocytes.
AB  - Coinfection with the human immunodeficiency virus (HIV) and Treponema pallidum
      may predispose to accelerated neurosyphilis. The mechanism underlying this
      interaction is undefined, but usually presumed to result from HIV-induced
      suppression of cell-mediated immunity as reflected in the CD4 T-lymphocyte count.
      We report a patient infected with HIV who developed aggressive neurosyphilis
      despite a CD4 count of 1000/mm3. The CD4 cells constituted 17% of his total
      lymphocytes. Our case suggests that while severe neurosyphilis can occur in HIV
      infected persons with normal absolute CD4 counts, the percentage of CD4 cells may
      be a better indicator of the risk of neurosyphilis. These observations are
      relevant to designing treatment strategies for patients coinfected with HIV and T
      pallidum based on measures of their immunocompetence.

PMID- 1350900
TI  - Long-term outcome in chronic schizophrenia.

PMID- 1350901
TI  - 63rd annual scientific meeting of the Aerospace Medical Association. Miami Beach,
      Florida, May 10-14, 1992. Abstracts.

PMID- 1350903
TI  - Functionally active homodimer of P-glycoprotein in multidrug-resistant tumor
      cells.
AB  - P-glycoprotein plays a key role in multidrug resistance of tumor cells. In order
      to elucidate the possible quarternary structure/function relationship of P
      glycoprotein, we treated multidrug-resistant human leukemia K562/ADM cells with
      the crosslinking reagent, disuccinimidyl suberate. In addition to 180K P
      glycoprotein, a 340K protein was immunoprecipitated with an anti-P-glycoprotein
      monoclonal antibody, MRK-16. The 340K protein is most probably a dimeric P
      glycoprotein, since only the 180K P-glycoprotein was immunoprecipitated with MRK
      16 when K562/ADM cells were treated with the cleavable crosslinking reagent,
      dithiobis(succinimidylpropionate), and analysed under reduced conditions. The
      dimeric P-glycoprotein was photolabeled with [3H]azidopine like the 180K
      monomeric P-glycoprotein and the photolabeling was inhibited by excess amount of
      vincristine and verapamil. The dimeric P-glycoprotein could be a functionally
      active form of the protein involved in the transport of antitumor agents.

PMID- 1350904
TI  - Cloning and nucleotide sequence of a full-length cDNA for human liver gamma
      glutamylcysteine synthetase.
AB  - We have cloned and sequenced a full-length cDNA for human liver gamma
      glutamylcysteine synthetase (GCS), the rate-limiting enzyme in glutathione
      biosynthesis. The cDNA consists of 2634 bp containing an open reading frame
      encoding a protein of 367 amino acids and having a calculated M(r) = 72,773. The
      nucleotide sequence of the cDNA for human liver GCS shares an 84% overall
      similarity with the composite rat GCS sequence deduced from three overlapping
      partial cDNAs (Yan and Meister, JBC 265: 1588-1593, 1990). The deduced amino acid
      sequences are 94% similar. Comparison of Northern blots of total RNA isolated
      from rat kidney or liver with that from human kidney revealed the GCS mRNA to be
      larger in the human tissue (approximately 4.0 kb vs. approximately 3.7 kb). (The
      sequence for the human liver GCS cDNA has been assigned accession number M90656
      in GenBank/EMBL databases.

PMID- 1350902
TI  - Transport of L-glutamine and L-glutamate across sinusoidal membranes of rat
      liver. Effects of starvation, diabetes and corticosteroid treatment.
AB  - There is increasing evidence that membrane transporters for glutamine and
      glutamate are involved in control of liver metabolism in health and disease. We
      therefore investigated the effects of three catabolic states [starvation (60 h),
      diabetes (4 days after streptozotocin treatment) and corticosteroid (8-day
      dexamethasone) treatment] associated with altered hepatic amino acid metabolism
      on the activity of glutamine and glutamate transporters in sinusoidal membrane
      vesicles from livers of treated rats. In control preparations, L-[14C]glutamine
      uptake was largely Na(+)-dependent, but L-[14C]glutamate uptake was largely Na(+)
      independent. Vmax. values for Na(+)-dependent uptake of glutamine and/or
      glutamate exceeded control values (by about 2- and 12-fold respectively) in liver
      membrane vesicles from starved (glutamine), diabetic (glutamate) or steroid
      treated (glutamine and glutamate) rats. The Km values for Na(+)-dependent
      transport of glutamine or glutamate and the rates of their Na(+)-independent
      uptake were not significantly altered by any treatment. Na(+)-independent
      glutamate uptake appeared to include a dicarboxylate-exchange component. The
      patterns of inhibition of glutamine and glutamate uptake by other amino acids
      indicated that the apparent induction of Na(+)-dependent amino acid transport in
      catabolic states included increased functional expression of systems A, N (both
      for glutamine) and X-ag (for glutamate). The results demonstrate that conditions
      resulting in increased secretion of catabolic hormones (e.g. corticosteroid,
      glucagon) are associated with increased capacity for Na(+)-dependent transport of
      amino acids into liver cells from the blood. The modulation of hepatic
      permeability to glutamine and glutamate in these situations may control the
      availability of amino acids for intrahepatic metabolic processes such as
      ureagenesis, ammonia detoxification and gluconeogenesis.

PMID- 1350906
TI  - Major histocompatibility complex genes and susceptibility to systemic lupus
      erythematosus in southern Chinese.
AB  - OBJECTIVE: To investigate the predisposing role of major histocompatibility
      complex (MHC) genes to systemic lupus erythematosus (SLE) in a Chinese
      population. METHODS: Polymorphism in the HLA-DRB, DQB, complement component C4,
      and 21-hydroxylase genes was analyzed by restriction fragment length polymorphism
      analysis and oligonucleotide probing of in vitro-amplified DNA from 88 Chinese
      patients with SLE and 69 matched control subjects. RESULTS: HLA-DRw15 and DQw1
      were significantly more frequent in patients (corrected P less than 0.006,
      relative risk 5.2), but none of the 9 sequence variants of DQw1 were increased.
      The C4A gene deletion usually associated with SLE in Caucasoid and black patients
      was absent from all Chinese subjects, but possession of other C4 deletions and of
      DRw15 conferred the greatest risk (relative risk = 8.3). CONCLUSION: Different
      MHC haplotypes predispose to lupus in Chinese than in other ethnic groups. Our
      data suggest that the susceptibility lies at, or telomeric to, the DR locus, and
      that DRw15 and C4 deletions may act synergistically in conferring disease
      susceptibility.

PMID- 1350905
TI  - Effects of buthionine sulfoximine and diethyl maleate on glutathione turnover in
      the channel catfish.
AB  - Despite the growing use of fish in toxicological studies, little is known
      regarding glutathione (GSH) metabolism and turnover in these aquatic species.
      Therefore, we examined GSH metabolism in the liver and gills of channel catfish
      (Ictalurus punctatus), a commonly employed aquatic toxicological model. Treatment
      of channel catfish with L-buthionine-S,R-sulfoximine (BSO, 400 or 1000 mg/kg,
      i.p.), an inhibitor of GSH biosynthesis, did not deplete hepatic GSH in channel
      catfish. In addition, hepatic GSH concentrations did not fluctuate in catfish
      starved for 3 days, indicating relatively slow turnover of hepatic GSH. However,
      hepatic GSH concentrations were reduced significantly (P less than 0.05) after 7
      days of starvation. Administration of the thiol alkylating agent diethyl maleate
      (DEM, 0.6 mL/kg, i.p.) resulted in depletion of 85% of hepatic GSH at 6 hr post
      DEM, with complete GSH recovery observed at 24 hr post-DEM. Co-administration of
      BSO and DEM (1000 mg/kg, 0.6 mL/kg, respectively) substantially depleted gill GSH
      and eliminated detectable liver GSH. Following BSO/DEM, GSH recovery in hepatic
      mitochondria occurred more rapidly than did liver cytosolic GSH. gamma
      Glutamylcysteine synthetase (GCS) activities were comparable in the 10,000 g
      supernatants of catfish liver and gills (204 +/- 21 and 268 +/- 20 nmol/min/mg
      protein, respectively) whereas gamma-glutamyltranspeptidase (GGT) activity was
      not detected in the 600 g post-nuclear fraction of either liver or gills. In
      conclusion, i.p. administration of DEM was an effective means for achieving short
      term hepatic GSH depletion in channel catfish, whereas co-administration of BSO
      and DEM elicited prolonged and extensive hepatic GSH depletion in this species.
      Like rodents, channel catfish maintained physiologically distinct hepatic
      mitochondrial and cytosolic GSH pools, and also regulated hepatic GSH levels by
      in situ hepatic GSH biosynthesis. However, unlike rodents, there was no evidence
      for a labile hepatic cytosolic GSH pool in channel catfish. These similarities
      and differences need to be considered when designing toxicological studies
      involving the GSH pathway in channel catfish and possibly other fish species.

PMID- 1350907
TI  - Detection and quantification of anti-Ki antibodies by enzyme-linked immunosorbent
      assay using recombinant Ki antigen.
AB  - OBJECTIVE: To establish an enzyme-linked immunosorbent assay (ELISA) for
      detecting anti-Ki antibody, using a bovine recombinant Ki antigen, and studying
      its specificity. METHODS: Sera from 220 patients with various connective tissue
      diseases were screened, and a prospective study of fluctuations in anti-Ki
      antibody and clinical course of a woman with systemic lupus erythematosus (SLE)
      was analyzed, by ELISA: RESULTS: Anti-Ki antibodies were present in 18.9% of
      patients with SLE. The titer of anti-Ki antibody in the woman with SLE rose
      before the onset of pericarditis and pleuritis in this longitudinal study.
      CONCLUSION: ELISA using a recombinant Ki antigen is useful for the diagnosis of
      SLE, and it might be useful in estimating disease activity in patients with SLE.

PMID- 1350908
TI  - Increased levels of circulating intercellular adhesion molecule 1 in Kawasaki
      disease.
AB  - OBJECTIVE: We investigated whether levels of intercellular adhesion molecule 1
      (ICAM-1) antigen shed into the circulation increase during acute Kawasaki disease
      (KD). We also compared ICAM-1 levels in acute KD with those in anaphylactoid
      purpura (AP) and in measles. METHODS: Serum ICAM-1 levels were measured by a
      double-determinant immunoassay using 2 monoclonal antibodies in the FAST (Falcon
      assay screening test) system. Serum levels of tumor necrosis factor alpha (TNF
      alpha) were measured by a specific and sensitive sandwich enzyme immunoassay.
      RESULTS: Patients with KD, but not those with AP or measles, had increased levels
      of shed ICAM-1 antigen in serum samples obtained during acute stages. Moreover,
      during the acute stage, KD patients with coronary artery lesions (CAL) had still
      higher levels of shed ICAM-1 than did those without CAL. We found a positive
      correlation between serum levels of shed ICAM-1 and levels of TNF alpha during
      acute KD. CONCLUSION: Our findings suggest that the serum ICAM-1 level is an
      important immunologic parameter for determining the severity of vascular damage
      during acute KD.

PMID- 1350909
TI  - Successful treatment of human immunodeficiency virus-associated Reiter's syndrome
      with sulfasalazine.

PMID- 1350910
TI  - [Association of a secreting oncocytic tumor of the kidney and a parathyroid
      adenoma].
AB  - An unusual association of a secreting renal oncocytoma and a parathyroid adenoma
      is described. The high level of hypercalcemia and of blood parathormone (PTH 44
      68), partially reduced by nephrectomy and totally normalized by
      parathyroidectomy, as well as the renal tumor PTH evaluation and the
      ultrastructural features showing secretory granules in oncocytic cells of kidney,
      advocate for a double site of PTH secretion. Removal of both tumors permits a
      complete recovering.

PMID- 1350911
TI  - The Hantaviruses, etiologic agents of hemorrhagic fever with renal syndrome: a
      possible cause of hypertension and chronic renal disease in the United States.

PMID- 1350912
TI  - [The controversy: use of beta-stimulants and mortality in asthma: analysis of a
      recent article].

PMID- 1350913
TI  - Regulation and function of cyclic nucleotides.
AB  - Recent work has greatly expanded our knowledge of the structure, regulation and
      diversity of enzymes involved in the synthesis and degradation of cyclic
      nucleotides. This review focuses on recent work that provides insight into the
      structure and function of the cyclases and phosphodiesterases that regulate
      cyclic nucleotide metabolism. Particular emphasis is given to the roles played by
      multiple isoforms of each enzyme system.

PMID- 1350914
TI  - [Location of ctDNA fragment related to CMS in Brassica napus L. var. xiangai].
AB  - The ctDNA of sterile line and its maintainer from Brassica napus L. var. xiangai
      were digested by restriction endonucleases EcoRI, BamHI, PstI and SmaI. Only one
      special fragment E3.2kb was observed in EcoRI restriction pattern of maintainer.
      After being eluted, this fragment was incubated with plasmid pUC9 and then
      transformed E. coli JM83. Through colour screening, clony hybridization and
      electrophoretic analyses, the special clone carrying E3.2 was obtained. The rRNA
      gene probe was used to hybridize with the EcoRI restriction pattern. The result
      showed that E3.2kb fragment is homologous to rRNA gene. And then, we use E3.2
      fragment as probe to hybridize with rRNA gene digested by BamHI, EcoRI, SalII,
      BglII, HindIII and PstI. According to rRNA gene map, E3.2 fragment was located at
      the leader sequence of 16S rRNA gene, from +2.0kb to +5.4kb. Because this 3.4kb
      region was in the inverted repeat region of ctDNA and it is homologous to E3.2kb
      that related to CMS. So probably CMS is related to this 3.4kb region in the
      inverted repeat region of ctDNA.

PMID- 1350915
TI  - Geographical subtypes demonstrated by RFLP following PCR in the LTR region of
      HTLV-I.
AB  - It has been demonstrated that specific mutations, localized in the long terminal
      repeat (LTR) region of HTLV-I, allowed to propose the existence of three HTLV-I
      subtypes. Because some of these mutations created or suppressed the restriction
      sites for ApaI, NdeI, DraI, SacI, MaeIII, and MaeII enzymes, these endonucleases
      were used for characterization of further 30 HTLV-I isolates. Seventeen proviral
      DNA from Japan, five from the Caribbean, one each from French Guyana, the United
      States, and China, two from Ivory Coast, and three from Zaire were tested. The
      DNA used were extracted from 26 in vivo peripheral blood mononuclear cell samples
      and from four cell lines obtained from two Japanese, one Chinese, and one North
      American patients. Digestions were performed on amplified DNA of the LTR region
      (nucleotides 31-768). The results confirm the existence of three subtypes of HTLV
      I according to LTR sequences. Subtype I was observed only in patients from the
      Ivory Coast and Zaire. Subtype II was found in the patient from the French West
      Indies, and in 33% of the samples from Japan. Subtype III was most often observed
      in the Japanese but also in the Zairian patients.

PMID- 1350916
TI  - Brucella abortus stimulates human T cells from uninfected and HIV-infected
      individuals to secrete IFN gamma: implications for use of Brucella abortus as a
      carrier in development of human vaccines.
AB  - Brucella abortus has been characterized as a T-independent type 1 antigen/carrier
      in human and murine antibody responses. In this report it is shown that BA can
      activate human CD3+ T cells to secrete interferon-gamma (IFN gamma). Unlike
      mitogens, such as phytohemagglutinin, this stimulation was associated with
      minimal T-cell proliferation or upregulation of interleukin-2 (IL-2) receptor.
      Monocytes inhibited BA-mediated IFN gamma secretion since their removal resulted
      in increased responses, whereas adding monocytes back to cultures caused
      inhibition. BA elicited IFN gamma from CD4+ and CD8+ T cells, although CD4+ T
      cells secrete significantly more (p less than 0.05) IFN gamma than CD8+ T cells.
      The ability of BA to elicit IFN gamma from human T cells was inhibited in the
      presence of anti-Tac, suggesting that BA also induces IL-2 secretion and that IL
      2 is involved in BA-mediated IFN gamma secretion. Detectable IL-2 secretion was
      induced by BA in the presence of anti-Tac. Exogenous IL-2 acted synergistically
      with BA to enhance IFN gamma secretion, suggesting that the amount of IL-2
      released by BA alone was insufficient for optimal IFN gamma release. Furthermore,
      addition of IL-2 to T cells from individuals with poor or absent responses to BA,
      including individuals infected with HIV-1, restored their ability to secrete IFN
      gamma in response to BA. These data indicate that BA is capable not only of
      activating human B cells but can also induce T cells, probably of the TH1
      phenotype, to secrete IFN gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350918
TI  - Pseudoaneurysm of the gastroduodenal artery arising within a pancreatic
      pseudocyst.
AB  - A case is presented of a 41-year-old man admitted for obstructive jaundice. Work
      up revealed a pseudocyst of the pancreatic head which contained a large
      pseudoaneurysm of the gastroduodenal artery. After an unsuccessful attempt at
      embolization, the patient was treated with an uncomplicated
      pancreaticoduodenectomy.

PMID- 1350917
TI  - Clinical trials referral resource. Clinical trials with 2-chlorodeoxyadenosine.

PMID- 1350919
TI  - Takayasu's arteritis and temporal arteritis.

PMID- 1350920
TI  - Glycosylinositol phospholipid anchors of the scrapie and cellular prion proteins
      contain sialic acid.
AB  - The only identified component of the scrapie prion is PrPSc, a glycosylinositol
      phospholipid (GPI)-linked protein that is derived from the cellular isoform
      (PrPC) by an as yet unknown posttranslational event. Analysis of the PrPSc GPI
      has revealed six different glycoforms, three of which are unprecedented. Two of
      the glycoforms contain N-acetylneuraminic acid, which has not been previously
      reported as a component of any GPI. The largest form of the GPI is proposed to
      have a glycan core consisting of Man alpha-Man alpha-Man-(NeuAc-Gal-GalNAc-)Man
      GlcN-Ino. Identical PrPSc GPI structures were found for two distinct isolates or
      "strains" of prions which specify different incubation times, neuropathology, and
      PrPSc distribution in brains of Syrian hamsters. Limited analysis of the PrPC GPI
      reveals that it also has sialylated glycoforms, arguing that the presence of this
      monosaccharide does not distinguish PrPC from PrPSc.

PMID- 1350921
TI  - Identification of an essential cysteine in the reaction catalyzed by aspartate
      beta-semialdehyde dehydrogenase from Escherichia coli.
AB  - The enzyme L-aspartate-beta-semialdehyde dehydrogenase from Escherichia coli has
      been studied by oligonucleotide-directed mutagenesis. The focus of this
      investigation was to examine the role of a cysteine residue that had been
      previously identified by chemical modification with an active site directed
      reagent (Biellmann et al. (1980) Eur. J. Biochem. 104, 59-64). Substitution of
      this cysteine at position 135 with an alanine results in complete loss of enzyme
      activity. However, changing this cysteine to a serine yields a mutant enzyme with
      a maximum velocity that is 0.3% that of the native enzyme. This C135S mutant has
      retained essentially the same affinity for substrates as the native enzyme, and
      the same overall conformation as reflected in identical behavior on gel
      electrophoresis and in identical fluorescence spectra. The pH profile of the
      native enzyme shows a loss in catalytic activity upon protonation of a group with
      a pKa value of 7.7. The same activity loss is observed at this pH with the serine
      135 mutant, despite the differences in the pKa values for a cysteine sulfhydryl
      and a serine hydroxyl group that have been measured in model compounds. This
      observed pKa value may reflect the protonation of an auxiliary catalyst that
      enhances the reactivity of the active site cysteine nucleophile in the native
      aspartate-beta-semialdehyde dehydrogenase.

PMID- 1350922
TI  - Assay for N-acetylmuramyl-L-alanine amidase in serum by determination of muramic
      acid released from the peptidoglycan of Brevibacterium divaricatum.
AB  - A method is reported for the determination of N-acetylmuramyl-L-alanine amidase
      in serum. Muramic acid, released from the interpeptide bridges of Brevibacterium
      divaricatum peptidoglycan, is measured by a modified colorimetric method. Using
      this procedure, it was possible to determine N-acetylmuramyl-L-alanine amidase in
      aliquots of less than 10 microliters human serum with an incubation time of 10
      min. Amidase activity was found in all the sera tested (n = 11). The relevance of
      this simple and fast assay is discussed.

PMID- 1350923
TI  - Handedness as a risk factor for neuroleptic-induced movement disorders.

PMID- 1350924
TI  - Clozapine and akathisia.

PMID- 1350925
TI  - Prophylaxis for Pneumocystis carinii pneumonia in patients infected with human
      immunodeficiency virus.
AB  - Following the initial observation by Dr. Margaret Fischl that trimethoprim
      sulfamethoxazole can prevent Pneumocystis carinii infection in patients with
      Kaposi's sarcoma, initiating prophylaxis for pneumocystic infection in all
      patients with less than 200 CD4+ cells/mm3 has become accepted practice. This
      prophylactic intervention has been found not only to reduce the development of
      pneumonia due to P. carinii but also to prolong life. Drs. Henry Masur and Joseph
      A. Kovacs first reviewed prophylaxis for P. carinii pneumonia in patients
      infected with the human immunodeficiency virus for the AIDS Commentary 3 years
      ago. They have updated that initial review for this AIDS Commentary, placing
      currently available information into concise clinical perspective and detailing a
      rational plan for the clinician to follow based on results of recent studies.

PMID- 1350926
TI  - A pharmacokinetic study of sulphasalazine and two new formulations of mesalazine.
AB  - We have examined the pharmacokinetics of enteric coated sulphasalazine compared
      with two new formulations of mesalazine. These consisted of microgranules of
      mesalazine coated with Eudragit S in a concentration of either 20 or 25% dry
      lacquer substance; these in turn were enclosed in capsules coated with Eudragit
      L. In-vitro dissolution studies of coated microgranules showed that drug release
      was pH dependent. Studies in 7 normal volunteers showed median peak
      concentrations of 5-amino-salicylic acid and N-acetyl-5-amino-salicylic acid
      occurred at about 6 hours with both microgranular preparations, compared with
      sulphasalazine at 15 h. The microgranule formulation coated with 20% Eudragit S
      gave serum levels and overall systemic absorption similar to values with
      sulphasalazine. This new formulation may be of value for delivering mesalazine
      and other therapeutic agents to the colon.

PMID- 1350928
TI  - Biophysical discussions on biophysics and recombinant DNA: problems, strategies,
      and new questions.

PMID- 1350927
TI  - Effects of acetorphan, an antidiarrhoeal enkephalinase inhibitor, on oro-caecal
      and colonic transit times in healthy volunteers.
AB  - Acetorphan is a potent enkephalinase inhibitor displaying antidiarrhoeal activity
      attributable to its intestinal antisecretory action mediated by endogenous
      enkephalins. The effect of acetorphan on digestive motility was studied in 12
      healthy volunteers. Oro-caecal transit time was evaluated using the
      sulphasalazine/sulphapyridine method and colonic transit times using radiopaque
      markers. These measurements were successively performed after one week treatment
      with an antidiarrhoeal dose of acetorphan (100 mg t.d.s.) or placebo. There was
      no significant modification in transit time linked to acetorphan treatment: total
      oro-caecal times were 303 +/- 32 min vs. 287 +/- 27 min and colonic transit times
      25.8 +/- 5.8 h vs. 31.3 +/- 5.5 h after acetorphan and placebo, respectively
      (means +/- S.E.M.). There was no significant modification either in right
      colonic, left colonic or rectosigmoid segmental transit times, or in the mean
      number of stools. These results, consistent with those from animal studies,
      confirm that, unlike classical antidiarrhoeal mu opiate receptor agonists, which
      act by delaying intestinal transit, acetorphan does not affect the transit.
      Antidiarrhoeal activity not accompanied by a delayed intestinal transit could
      have beneficial therapeutic consequences in the management of infectious
      diarrhoea. In addition, we show that the sulphasalazine and radiopaque markers
      methods can be simultaneously applied in the same study.

PMID- 1350929
TI  - Signal transduction in mesangial cells.
AB  - Phenotype, growth, and functional characteristics of glomerular mesangial
      "myofibroblasts" are under the control of multiple hormones, vasoactive agents,
      autacoids, and cytokines. Several parallel signal transduction pathways couple
      receptor occupancy with functional changes, including phospholipases C, A2, and D
      breakdown of membrane phospholipids, and adenylate/guanylate cyclase activation.
      Changes of cytosolic ion concentrations, cyclic nucleotide accumulation, and
      eicosanoid biosynthesis are currently interpreted as intracellular signals for
      protein kinase activation. Phosphorylation of multiple substrates by
      serine/threonine kinases C, A, and G or by tyrosine kinases directly coupled to
      receptors, is a final step in cell activation. Cross-talk between signal
      transduction pathways, along with the release of eicosanoids and cytokines acting
      as intercellular mediators, provides the potential for interactive regulation of
      glomerular cell functions.

PMID- 1350930
TI  - The glomerular mesangium: from cell biology to clinics. Conference. Fiuggi Terme,
      Italy, September 27-28, 1991.

PMID- 1350933
TI  - Self-injury resulting in amputation among vascular patients: a retrospective
      epidemiological study.
AB  - In the course of 24 months, 164 nontraumatic vascular amputees were accepted for
      prosthetic rehabilitation; 120 (73%) were diabetic and 44 (27%) non-diabetic.
      Subjects were divided into two groups, the first consisting of 114 with
      spontaneous foot infection or gangrene and the second of 50, of whom 44 were
      diabetic and six had peripheral arterial disease on its own. Sixty-five per cent
      of all amputees had fewer than nine years of formal education and 46% were in the
      low-income bracket, but no significant relationship was found between mechanism
      of self-injury and level of education and income. All patients in the second
      group were able to detail ways in which they had injured their feet. The
      relationship between the mechanism of self-injury and the presence of diabetes
      mellitus was found to be highly significant. By instructing in better self-care
      it may be possible to prevent or at least postpone amputation in these patients.

PMID- 1350931
TI  - Characterization of the gene encoding the plastid-located glutamine synthetase of
      Phaseolus vulgaris: regulation of beta-glucuronidase gene fusions in transgenic
      tobacco.
AB  - The gln-delta gene, which encodes the plastid-located glutamine synthetase of
      Phaseolus vulgaris, was cloned and its promoter region was sequenced. Primer
      extension analysis was used to map the two major transcription initiation sites
      which are about 90 nucleotides apart. A fusion of 2.3 kb of the upstream region
      of the gln-delta gene to the reporter gene uidA encoding beta-glucuronidase was
      shown to be expressed in the chlorophyllous cell types of leaves and stems and in
      the root meristem region of transgenic tobacco. Analysis of a series of three 5'
      promoter deletion fusions revealed the presence of a region essential for
      promoter activity between -786 and -327 and regions involved in tissue-specific
      regulation and light regulation between -786 and +43.

PMID- 1350934
TI  - Clinical meaning of GGT activity in follow-up of patients with alcohol-related
      liver injury and cholestasis.
AB  - The dynamics of GGT was investigated in three groups of patients after removing
      some primary causes of GGT increase. Group A included 34 patients with alcohol
      related liver disease, group B included 16 patients with alcoholic liver injury
      and cholestasis, caused by concomitant alcoholic pancreatitis and group C
      included 17 patients with extrahepatic cholestasis, caused by
      choledocholithiasis. Follow-up assays of GGT were performed on the 7th, 14th and
      30th days. Our results showed that the dynamics of GGT was more rapid after
      removing the cause for cholestasis than in stopping alcohol consumption in
      patients with chronic liver diseases. On the 14th day more than a 50% decrease in
      GGT activity was noted in 20% of the patients from groups A and B and in almost
      all cases from group C. On the 30th day, the reference range of GGT was not
      attained by any of the patients with liver disease nor in five patients from
      group C. No significant correlation was found between the severity of liver
      damage and the extent of GGT increase at the beginning and at the end of the
      follow-up period.

PMID- 1350932
TI  - cDNA, amino acid and carbohydrate sequence of barley seed-specific peroxidase BP
      1.
AB  - The major peroxidase of barley seed BP 1 was characterized. Previous studies
      showed a low carbohydrate content, low specific activity and tissue-specific
      expression, and suggested that this basic peroxidase could be particularly useful
      in the elucidation of the structure-function relationship and in the study of the
      biological roles of plant peroxidases (S.K. Rasmussen, K.G. Welinder and J.
      Hejgaard (1991) Plant Mol Biol 16: 317-327). A cDNA library was prepared from
      mRNA isolated from seeds 15 days after flowering. Full-length clones were
      obtained and showed 3' end length variants, a G+C content of 69% in the
      translated region, a 90% G or C preference in the wobble position of the codons
      and a typical signal peptide sequence. N-terminal amino acid sequencing and
      sequence analysis of tryptic peptides verified 98% of the sequence of the mature
      BP 1 which contains 309 amino acid residues. BP 1 is the first characterized
      plant peroxidase which is not blocked by pyroglutamate. BP 1 polymorphism was
      observed. BP 1 is less than 50% identical to other plant peroxidases which, taken
      together with its developmentally dependent expression in the endosperm 15-20
      days after flowering, suggests a unique biological role of this enzyme. The
      barley peroxidase is processed at the C-terminus and might be targeted to the
      vacuole. The single site of glycosylation is located near the C-terminus in the N
      glycosylation sequon -Asn-Cys-Ser- in which Cys forms part of a disulphide
      bridge. The major glycan is a typical plant modified-type structure, Man alpha 1
      6(Xyl beta 1-2)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-3)GlcNAc. The BP 1 gene
      was RFLP-mapped on barley chromosome 3, and we propose Prx5 as the name for this
      new peroxidase locus.

PMID- 1350935
TI  - Haemodynamic effects of roxatidine, an H2-receptor antagonist.
AB  - The haemodynamic effects of roxatidine were investigated in 12 patients with
      congestive heart failure (New York Heart Association class II) in a placebo
      controlled, double-blind, randomized, cross-over study. Impedance and
      mechanocardiography were determined following successive 7-day treatment periods
      with placebo and roxatidine 150 mg once daily. Comparison with placebo values
      showed roxatidine to significantly increase the preejection period (109.7 +/- 2.7
      ms versus 117.3 +/- 2.7 ms, 1.5 h after administration). Heart rate and blood
      pressure remained the same. In contrast to other, newer H2-receptor antagonists,
      which decrease stroke volume and/or cardiac output, roxatidine did not reduce
      these parameters but increased the preejection period and the ratio of the
      preejection period to the left ventricular ejection time, indicating a slight
      negative influence on cardiac performance.

PMID- 1350936
TI  - Disappearance of a pituitary tumor after 15 months of treatment with CV 205-502,
      a new dopamine agonist.
AB  - We report the case of a 27-year-old woman with a prolactin-secreting macroadenoma
      of the pituitary gland who was under treatment with a new dopamine agonist,
      Sandoz CV 205-502. Immediately after diagnosis of a 12 x 10 mm intrasellar
      prolactinoma, treatment with CV 205-502 was begun at a daily dose of 0.075 mg.
      Under this low dose, prolactin in the serum normalized after 4 weeks, the initial
      hormone value being 189.9 ng/ml. After 6 months of therapy there was still a 6 x
      6 mm tumor, and after 15 months of treatment the pathological process could no
      longer be observed with magnetic resonance imaging. In the 20th month of therapy
      the patient became pregnant. An ovulatory menstrual cycle had been present for a
      few months.

PMID- 1350937
TI  - Isolation of clobazam-orosomucoid complexes from patients' sera.
AB  - Orosomucoid, a member of the lipocalin family, may function in the in vivo
      transport of lipophilic compounds such as basic and neutral drugs. We describe
      the identification of 7-chloro-1-methyl-1,5-benzodiazepine-2,4-dione (clobazam)
      bound to the serum orosomucoid from individuals actively taking this
      tranquillizer. This suggests not only that other endogenous factors limit access
      to the benzodiazepine binding site on human serum albumin, but also that the
      differential binding of benzodiazepines and their metabolites by orosomucoid
      should be considered in determining therapeutic doses, particularly in the acute
      phase response.

PMID- 1350939
TI  - Incidence of mixed chimerism using busulfan/cyclophosphamide containing regimens
      in allogeneic bone marrow transplantation.
AB  - The incidence of mixed chimerism (MC) following allogeneic bone marrow
      transplantation (allo-BMT) is in part a measure of the marrow ablative effect of
      preparative regimens. Although the incidence of MC has been reported for many
      patients treated with total body irradiation (TBI), limited data for
      busulfan/cyclophosphamide (BU/CY) recipients have been examined. We performed
      restriction fragment length polymorphism (RFLP) analysis on 68 peripheral blood
      samples from 26 patients treated with BU/CY prior to allo-BMT for chronic
      myelogenous leukemia or acute myeloid leukemia. MC was detected in four of 26
      patients for an overall incidence of 15.4%. Three of four MC patients are alive
      with no evidence of disease at 263 to 795 days post-transplantation. A fourth
      patient is alive at day 501 but developed CNS relapse at day 274. The level of
      recipient origin cells was less than 10% in all samples and detectable MC was
      transitory with an RFLP pattern that reverted to full chimerism. These results
      are comparable to those reported for TBI-containing regimens in patients
      receiving non-T cell-depleted bone marrow. The efficacy of BU/CY in conjunction
      with a T cell depletion still requires exploration.

PMID- 1350938
TI  - Comparison of haematological recovery times and supportive care requirements of
      autologous recovery phase peripheral blood stem cell transplants, autologous bone
      marrow transplants and allogeneic bone marrow transplants.
AB  - The haematological recovery time, infection rate and supportive care requirements
      of patients receiving recovery phase autologous peripheral blood stem cell
      transplants (APBSCT) (n = 38), autologous bone marrow transplants (autoBMT) (n =
      13) and allogeneic bone marrow transplants (alloBMT) (n = 14) were compared with
      respect to the time post-transplant to reach 0.1, 0.5 and 2.0 x 10(9)
      neutrophils/l and 50 and 150 x 10(9) platelets/l, the length of hospitalization,
      fever and antibiotic use, the incidence of documented infection and the number of
      red cell and platelet transfusions. The APBSCT group had a significantly more
      rapid recovery of neutrophils and platelets and their supportive care
      requirements were significantly less than the autoBMT and the alloBMT groups.
      There was no difference between the latter two groups. The most significant
      variables contributing to the differences in haematological recovery times were
      the granulocyte-macrophage progenitor (CFU-GM) dose infused and, to a lesser
      extent, patient age. The APBSCT group received a higher CFU-GM dose of 87 +/- 12
      x 10(4)/kg BW compared with 12 +/- 5 and 17 +/- 3 x 10(4)/kg BW in the autoBMT
      and the alloBMT groups, respectively (p = 0.0001). Patient age showed a negative
      correlation with the rate of recovery because the APBSCT group, which recovered
      faster was also older (48 +/- 2 years, compared with 33 +/- 3 and 31 +/- 2,
      respectively, p = 0.0001). On multivariate analysis, CFU-GM dose was the only
      variable to show a significant correlation with all the haematological recovery
      endpoints studied in these 65 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350940
TI  - Late life schizophrenia and its treatment: pharmacologic issues in older
      schizophrenic patients.
AB  - Schizophrenia in late life includes both chronic early-onset schizophrenia and
      late-onset schizophrenia. Treatment with neuroleptics in relatively low doses is
      often useful in controlling psychotic symptoms in these patients. The value of
      neuroleptics is limited, however, by the risks of side effects such as tardive
      dyskinesia.

PMID- 1350942
TI  - Proceedings of the 18th Collegium Internationale Neuro-Psychopharmacologicum
      Congress. Part B. Nice, France, June 28-July 2, 1992. Abstracts.

PMID- 1350941
TI  - Neuroendocrine differentiation in carcinoma of the prostate. Diagnostic,
      prognostic, and therapeutic implications.
AB  - Endocrine-paracrine cells of the prostate (also known as APUD or neuroendocrine
      cells) constitute, in addition to the basal and exocrine secretory cells, a third
      population of highly specialized epithelial cells in the prostate gland. These
      endocrine-paracrine cells contain, and most likely secrete, serotonin and
      calcitonin, as well as variety of other peptides. Little is known of the
      functional role of these cells, but they probably subserve a paracrine or local
      regulatory role. They may also regulate via endocrine, lumencrine, or neurocrine
      mechanisms. These endocrine-paracrine cells probably play a significant role
      during prostatic growth and differentiation as well as regulating the secretory
      process of the mature gland. Neuroendocrine differentiation in prostatic
      carcinoma occurs in the form of the relatively rare small cell carcinoma and
      carcinoid or carcinoid-like tumor, but most commonly as focal neuroendocrine
      differentiation in a conventional prostatic adenocarcinoma that is a very
      frequent, if not ubiquitous phenomenon, and reflects tumor cell heterogeneity
      mimicking the normal differentiation process. The world's literature on
      neuroendocrine differentiation in prostatic carcinoma is reviewed. Neuroendocrine
      differentiation in all types of prostatic carcinoma appears to correlate with a
      poor prognosis. This correlation is probably multifactorial and may relate to a
      positive correlation with grade, a direct resistance to hormonal manipulation,
      and/or autocrine/paracrine growth factor activity due to the secretion of
      neuroendocrine products. Neuron-specific enolase and chromogranin, as well as
      other neuroendocrine products, may be useful as serum markers in patients with
      prostatic carcinoma with neuroendocrine differentiation. New therapeutic
      strategies need to be developed to treat these tumors. This includes the use of
      specialized protocols that have been effective against neuroendocrine carcinomas
      arising in other organ systems.

PMID- 1350943
TI  - [Echo-Doppler evaluation of the internal mammary artery bypass on the left
      coronary artery: a 4-year follow-up].
AB  - In this study ultrasonographic techniques are suggested to monitor internal
      mammary artery bypass graft on the anterior descending coronary artery. One
      hundred and fourty patients were studied using 3 different ultrasonographic
      methods: zero-crossing continuous wave Doppler, fast Fourier transform (FFT)
      continuous wave Doppler and high resolution echo-Doppler. The patients underwent
      the ultrasonographic examinations 3 times a year for 4 years. By means of FFT
      Doppler analysis and echo-Doppler it was possible to perform the study in 138
      patients and by zero-crossing system in 127 patients. Ultrasonographic techniques
      showed pathologies of the graft in 17 (13%) patients: 15 with obstructive
      pathologies and 2 with haemodetournament of the second intercostal artery.

PMID- 1350944
TI  - Analysis of CD4 gene expression in human fetal brain and neuroblasts.
AB  - 1. The expression of the gene codifying for CD4, the most important human
      immunodeficiency virus type 1 (HIV-1) receptor molecule, was analyzed in 11 fetal
      brains at various gestational ages and in 9 human neuroblastoma (NB) cell lines.
      CD4 gene expression in fetal and malignant neural cells was then compared with
      that observed in a hematopoietic cell line and adult hippocampus. 2. In addition,
      CD4 mRNA was evaluated in two NB cell lines induced to differentiate in vitro
      with retinoic acid (RA) or 1-(5-isoquinolinyl-sulfonyl)-2-methyl piperazine (H7),
      a protein kinase C inhibitor. 3. All fetal brains and NB cell lines express a 1.8
      kb signal when hybridized with pT4BcDNA probe, while a 3.0-kb signal such as
      observed in hematopoietic human cells was found in 1 of 11 fetal brains and in 0
      of 9 NB cell lines. The 1.8-kb signal was lost in all analyzed poly(A)+ mRNA
      samples. 4. Moreover, CD4 gene expression was not induced in either RA- or H7
      treated NB cells at any tested time and dose. The analysis of NB cells by
      polymerase chain reaction failed to demonstrate CD4 expression in either poly(A)+
      or poly(A)- RNA. 5. In conclusion, the results show that the 1.8-kb signal
      observed in RNA extracted from fetal or transformed human neural cells is
      probably due to an aspecific hybridization. However, the gene codifying for CD4
      can rarely be expressed by fetal brain cells early during gestation, in still
      unclear circumstances.

PMID- 1350945
TI  - Nucleotide and deduced amino acid sequence of bovine adrenal medulla chromogranin
      B (secretogranin I).
AB  - 1. A novel 1745-dalton pyroglutamyl peptide (BAM-1745)6 was recently isolated and
      characterized from bovine adrenal medulla chromaffin granules. Its amino acid
      sequence was found to be 93% identical to residues 580-593 of human chromogranin
      B (secretogranin I). 2. Based on this sequence a degenerate oligonucleotide probe
      was synthesized and used to identify a 2.4-kb bovine adrenal medulla chromogranin
      B cDNA. 3. The deduced polypeptide is 647 amino acids long and begins with a
      putative signal sequence of 20 residues as in the human, rat, and mouse proteins.
      Also conserved in the bovine protein is a tyrosine residue which may be sulfated,
      two N-terminal cysteines, and many paired basic amino acids which may serve as
      sites of posttranslational processing. The peptide BAM-1745 is flanked by paired
      basic amino acids and therefore is most likely a product of posttranslational
      processing. Bovine chromogranin B is 67, 58, and 58% identical to the human, rat,
      and mouse chromogranin B proteins, respectively. 4. The carboxyl terminus of
      bovine chromogranin B, including BAM-1745, was found to be the most conserved
      region of the polypeptide and may identify it as an important functional domain.

PMID- 1350947
TI  - Annual Meeting of the Canadian Anaesthetists' Society. Toronto, Ontario, June 5
      9, 1992. Abstracts.

PMID- 1350946
TI  - Vasoactive intestinal polypeptide and acetylcholine coexist with neuropeptide Y,
      dopamine-beta-hydroxylase, tyrosine hydroxylase, substance P or calcitonin gene
      related peptide in neuronal subpopulations in cranial parasympathetic ganglia of
      rat.
AB  - Immunohistochemistry has been used to demonstrate that neuropeptide Y, dopamine
      beta-hydroxylase, calcitonin gene-related peptide or substance P are colocalized
      with vasoactive intestinal polypeptide and choline acetyltransferase in
      subpopulations of neurons in cranial parasympathetic ganglia of rat. These
      comprise the ciliary, sphenopalatine, otic, glossopharyngeal-vagal and internal
      carotid ganglia. In the ciliary and glossopharyngeal-vagal ganglia tyrosine
      hydroxylase is also found in such neurons. The findings emphasize that the
      combined localization of dopamine-beta-hydroxylase and neuropeptide Y or the
      presence of tyrosine hydroxylase is not exclusively a marker for peripheral
      adrenergic neurons. Further, the co-localization of calcitonin gene-related
      peptide and substance P is not a decisive indication that a neuron is sensory in
      nature. It is discussed whether the presence of the enzymes and peptides other
      than vasoactive intestinal polypeptide is a remnant of a different expression
      during ontogenesis or indicates target-specific functions in the adult.

PMID- 1350948
TI  - Update on postoperative pain management.

PMID- 1350949
TI  - Genetic alterations in the 61st codon of the H-ras oncogene isolated from
      archival sections of hepatic hyperplasias, adenomas and carcinomas in control
      groups of B6C3F1 mouse bioassay studies conducted from 1979 to 1986.
AB  - In order to better understand the molecular events in murine
      hepatocarcinogenesis, the frequency and types of mutations in the murine H-ras
      proto-oncogene isolated from 184 independent, spontaneously occurring hepatic
      lesions were determined. Hepatocellular foci, hyperplasias, adenomas and
      carcinomas were obtained from archival samples of control male (134 samples) and
      female (50 samples) B6C3F1 mice used in oncogenicity studies that were conducted
      at Lilly Research Laboratories from 1979 to 1986. The 61st codon region of the H
      ras oncogene from these sections was amplified using the polymerase chain
      reaction. Mutation frequencies were determined by restriction fragment length
      polymorphism analysis. The types of mutations were characterized by allele
      specific oligonucleotide hybridization and confirmed by DNA sequencing. Forty-two
      per cent of the carcinomas, 44% of the adenomas, 42% of the hyperplasias and 29%
      of the foci contained mutations at the 61 codon. The mutation spectra for the
      carcinomas, adenomas and hyperplasias consisted of mostly CAA-AAA transversions,
      followed by CAA-CGA transitions, followed by CAA-CTA transversions. These results
      demonstrate that: (i) the frequency of spontaneous mutations in the H-ras 61st
      codon is equivalent in murine hyperplasias, adenomas and carcinomas, and (ii) sex
      was not a determining factor in either the mutation frequency or mutation
      spectrum for the spontaneous lesions. If these lesions represent successive
      stages in the carcinogenic process, then these results suggest that mutations in
      the 61st codon of H-ras are early events in spontaneous murine
      hepatocarcinogenesis.

PMID- 1350951
TI  - The relationship of HIV-1 viral sequences detected by the polymerase chain
      reaction in haemophilic patients to clinical and other markers of infection.
AB  - A nested primer polymerase chain reaction (PCR) of pol gene sequences of human
      immunodeficiency virus-1 (HIV-1) was applied to whole blood of 31 haemophiliacs
      who were, or had been, positive for HIV p24 antibody (HIVAb) by enzyme linked
      immunosorbent assay (ELISA) and samples from 22 persistently HIVAb negative
      haemophiliacs who had been at risk of contracting HIV from treatment. The results
      were compared with those of p24 HIV antigen determination, T4 cell counts beta 2
      Microglobulin (beta 2M) levels and clinical evidence of progression of HIV
      disease. There was no discrepancy between the PCR results and past or present
      seropositivity for HIVAb. The qualitative PCR was more sensitive than the p24
      antigen assay but the presence of the latter was predictive of progression of
      infection as determined clinically and by falling T4 cell counts and rising
      levels of beta 2M. The results of the PCR are reassuring for HIVAb negative
      haemophiliacs at risk from treatment and to HIVAb negative sexual contacts of
      HIVAb positive persons.

PMID- 1350950
TI  - Differential ontogeny of functional dopamine and muscarinic receptors mediating
      presynaptic inhibition of neurotransmitter release and postsynaptic regulation of
      adenylate cyclase activity in rat striatum.
AB  - To study the ontogeny of functional striatal dopamine (DA) D2 and muscarinic
      receptors we determined the first appearance of the inhibitory effects of
      activation of autoreceptors on neurotransmitter release and that of postsynaptic
      receptors on adenylate cyclase activity in striatal slices of rat foetuses and
      pups. On embryonic day 17 (E17), activation of D2 receptors with LY 171555 (1
      microM) resulted in a 50% inhibition of the electrically evoked release of [3H]DA
      from superfused striata, indicating that D2 autoreceptors are functional at that
      time. Stimulation of adenylate cyclase activity with the Da D1 agonist SK&F 38393
      could also be determined in the striatum on E17. In contrast, inhibition of D1
      stimulated adenylate cyclase activity through activation of postsynaptic D2
      receptors did not occur until postnatal day 14 (P14), whereas activation of
      postsynaptic muscarinic receptors with oxotremorine (1 microM) resulted in 30%
      inhibition already on E17. Endogenous activation of muscarinic receptors with
      physostigmine (1 microM) was ineffective in the prenatal period, but its
      inhibitory effect on D1-stimulated adenylate cyclase increased strongly between
      P7 and P21. Inhibition of striatal [3H]acetylcholine (ACh) release by activation
      of muscarinic receptors could not be determined until P7, because the release of
      the neurotransmitter was not measurable before that day. But on P7, oxotremorine
      and physostigmine (as well as the D2 receptor agonist LY 171555) reduced the
      electrically evoked release of [3H]ACh from striatal slices. Taken together,
      these data show that there is a marked time difference between the coupling of D2
      receptors and that of the D1 and muscarinic receptors to adenylate cyclase in the
      developing striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1350952
TI  - Co-existence of von Willebrand's disease and haemophilia A.

PMID- 1350953
TI  - Effects of membrane plant sterols on excitable cell functions.

PMID- 1350954
TI  - The role of prostaglandin H synthase in 3-methylindole-induced pneumotoxicity in
      goat.
AB  - 1. Aspirin and indomethacin were used to investigate the role of prostaglandin H
      synthase (PHS) system in 3-methylindole (3MI)-induced pneumotoxicity. 2. A
      functional test was developed to detect the inhibitory effect of oral doses of
      aspirin and indomethacin on PHS activity based on thromboxane B2 (TXB2)
      production from thrombin-stimulated platelets in whole blood. 3. Goats which
      received oral doses of aspirin or indomethacin before administration of 3MI (0.1
      g 3MI/kg body wt) showed a reduced severity in clinical signs and pathological
      lesions in the lung than those that received 3MI alone. 4. There was no
      difference in the severity of the disease between the control and the aspirin
      treated animals if aspirin was given after 3MI administration. 5. The protective
      effect of inhibitors when administered before, but not after, 3MI dosing suggests
      it is the inhibition of PHS activity in activation of 3MI, not in production of
      prostanoids which prevented the disease process.

PMID- 1350955
TI  - Response of Xenopus laevis to cadmium administration.
AB  - 1. Levels of copper, zinc and cadmium have been determined in the plasma, liver
      and kidneys of Xenopus laevis. 2. Administration of cadmium by subcutaneous
      injection induces metallothionein synthesis in the liver of Xenopus laevis.
      Cadmium is found to accumulate in both liver and kidneys following injection. 3.
      Cadmium uptake, following injection, is biphasic, suggesting a saturable first
      phase uptake mechanism, followed by a linear second phase. 4. Zinc is displaced
      from the liver by administration of cadmium in a dose-dependent manner.

PMID- 1350956
TI  - Xenobiotic-metabolizing enzyme systems in test fish--IV. Comparative studies of
      liver microsomal and cytosolic hydrolases.
AB  - 1. The initial slopes of the substrate-activity curves of several hydrolases were
      determined in the microsomal and cytosolic fractions of the liver of several fish
      recommended by OECD for the regulatory testing of chemicals. 2. Inter-species
      differences ranged within a factor of 7-17 for the esterases and reached a factor
      of 60 for the amidase. Guppy and carp appeared endowed with hydrolase activities
      which, overall, are much higher than zebra fish, trout and golden orfe. 3. The
      comparison with the rat liver microsomal hydrolases strongly suggests that fish
      are endowed with similar or higher levels of A-esterase and with much less B
      esterase/amidase activities.

PMID- 1350957
TI  - Effect of diethyl maleate on glutathione, hepatic and renal cortical perfusion,
      and portal 6-ketoPGF1 alpha and TxB2 levels in swine.
AB  - 1. Effects of diethyl maleate (DEM) mediated glutathione (GSH) depletion on
      hepatic and renal cortical blood flow (perfusion), plasma GSH, and portal
      prostacyclin (6-ketoPGF1 alpha) and thromboxane (TxB2) were determined in
      anaesthetized swine. 2. Although DEM depleted hepatic GSH to 25% of control,
      plasma GSH increased 10-fold in comparison to controls. DEM caused a drop in
      blood pressure and renal cortical perfusion but had no effect on hepatic
      perfusion or portal 6-ketoPGF1 alpha or TxB2 levels. 3. Possibly, the unexpected
      rise in plasma GSH may have inhibited prostanoid synthesis, preventing any
      alterations in tissue perfusion that may have occurred following tissue GSH
      depletion.

PMID- 1350958
TI  - Properties of cyclic AMP-dependent inward current in two identified neurons of
      the snail Lymnaea stagnalis.
AB  - 1. Intracellular iontophoresis of cyclic AMP induces a slow, inward sodium
      current in identified neurons B1 and RPD1 of Lymnaea stagnalis, which is TTX
      insensitive and voltage independent. 2. High extracellular Ca2+ or Co2+ ions
      cause a reduction in the amplitude of the current, whereas low Ca2+ enhances it.
      3. Agents known to increase intracellular cyclic AMP lead to depolarization and
      increased activity in B1, but RPD1 is unaffected. 4. The properties of cyclic AMP
      stimulated inward current in neurons of L. stagnalis are compared with those of
      similar currents in other gastropod species.

PMID- 1350960
TI  - Effect of cyclosporine treatment on carnitine and myo-inositol in diabetic rats.
AB  - 1. The effect of long-term (20 wk) treatment of cyclosporine A (CyA) was studied
      in urine, blood, liver, kidney and pancreatic concentrations of acid-soluble
      carnitine and free myo-inositol in streptozotocin diabetic rats. 2. Diabetic rats
      excreted significantly higher concentrations of carnitine and myo-inositol; CyA
      prevented the urinary loss of carnitine but not myo-inositol. 3. Blood carnitine
      levels were not different between normal and diabetic rats, however, CyA
      significantly decreased these levels. Conversely, blood myo-inositol
      concentrations were higher in diabetic than in normal rats; CyA prevented this
      increase. 4. Hepatic concentrations of both carnitine and myo-inositol were
      increased in diabetic rats; CyA treatment caused even further increase. 5.
      Pancreas from diabetic rats contained less carnitine and myo-inositol compared to
      normal pancreas. CyA treatment did not affect pancreatic carnitine, but it
      normalized myo-inositol in diabetic rats. 6. The kidney carnitine or myo-inositol
      levels were not influenced either by diabetes or by CyA treatment. 7. These
      results suggest that CyA treatment causes changes in carnitine and myo-inositol
      concentrations in biologic fluids and certain tissues.

PMID- 1350959
TI  - Effects of temperature on the anaesthetic potency of halothane, enflurane and
      ethanol in Daphnia magna (Cladocera: Crustacea).
AB  - 1. The effects of temperature on the anesthetic potencies of halothane, enflurane
      and ethanol have been studied in the water flea Daphnia magna. 2. In the absence
      of anaesthetics, decreasing temperature resulted in decreased activity by the
      daphnids. 3. Potencies in the gas phase decreased with increasing temperature for
      all of the anaesthetics, while aqueous potency decreased for halothane and
      enflurane but increased for ethanol. 4. Enthalpy calculations suggest that the
      observed potency changes for the inhalational anaesthetics cannot be accounted
      for in terms of changing solubility in lipid bilayers but most likely reflect
      more specific interactions with animal target sites.

PMID- 1350961
TI  - Seasonal changes in subcellular distribution of zinc, copper, cadmium and
      metallothionein in the liver of bank vole (Clethrionomys glareolus): a possible
      essential role of cadmium and metallothionein in the hepatic metabolism of
      copper.
AB  - 1. An increase in total Zn concentration in the liver of sexually mature bank
      voles in spring and summer was primarily accompanied by an increase in Zn levels
      in the nuclear and mitochondrial-lysosomal fractions, while in immature voles in
      an analogous situation, Zn tended to concentrate mainly in the post-mitochondrial
      fraction. 2. Seasonal changes in Cu concentration in all subcellular fractions
      followed closely those of total hepatic Cu; however, the mitochondrial-lysosomal
      Cu underwent the most dramatic changes. 3. Multiple regression analysis between
      the concentration of metallothionein (MT) in the postmitochondrial fraction and
      the levels of Zn, Cu and Cd in the particular subcellular fractions showed that
      MT was principally induced by small amounts of Cd concentration of which in the
      liver ranged from 0.019 microgram/g in winter to 1.1 micrograms/g wet wt in
      spring. 4. The analysis revealed further that the level of MT in the post
      mitochondrial fraction concurrently decreased as total hepatic Cu, as well as
      mitochondrial-lysosomal Cu, increased. 5. The data indicate that MT, first
      induced by small amounts of Cd, is involved in the hepatic metabolism of Cu in
      bank voles; most probably the protein sequesters free Cu ions in cytoplasm and
      then transfer them into the mitochondrial-lysosomal fraction.

PMID- 1350962
TI  - Helix aspersa neurons maintain vigorous electrical activity when co-cultured with
      intact H. aspersa ganglia.
AB  - 1. Identified neurons from the right parietal lobe of the circumoesophageal
      ganglion of adult land snails, Helix aspersa, were isolated and placed in primary
      cell culture. 2. The individual neurons were removed from the right parietal lobe
      by microdissection without the aid of exogenous enzymes and plated on poly-L
      lysine coated coverslip in normal Helix Ringer's solution conditioned with Helix
      circumoesphageal ganglia. The neurons become firmly attached to the substrate and
      begin to extend processes within 6 hr. 3. The cells show a dramatic increase in
      electrical activity when they are co-cultured with intact Helix circumoesophageal
      ganglia (1 ganglion/ml). Co-cultured neurons have resting potentials between -45
      and -110 mV, comparable to in situ, show spontaneous action potential firing and
      respond to putative neurotransmitters. Heat-treated conditioned media was
      inactive. 4. When dopamine or serotonin (5-HT) are added, right parietal beating
      neurons, F14-F16 and F29-F32, (i) show a suppression of action potentials
      occurrence; (ii) a decrease in action potential amplitude and duration, and (iii)
      an increase in after-hyperpolarization. 5. Right parietal bursting neuron F1 in
      culture fire action potentials only in a beating mode. Dopamine addition to F1
      suppresses action potential occurrence and causes an increase in action potential
      after-hyperpolarization, but there is only a small decrease in duration of action
      potentials and no significant change in action potential amplitude. 5-HT addition
      to F1 increases the occurrence of action potentials with little or no change in
      action potential shape. 6. This primary cell culture method is an efficient
      system for doing biochemical and electrophysiological studies on individual,
      identified neurons.

PMID- 1350963
TI  - Effects of adenine nucleosides and nucleotides on the isolated heart of the snail
      Helix aspersa and the slug Arion ater.
AB  - 1. Adenine nucleosides and nucleotides were examined for pharmacological activity
      in hearts isolated from the snail Helix aspersa and the slug Arion ater. 2.
      Adenosine, AMP, ADP and ATP (above 100 microM) produced either an excitation or
      an inhibition in the isolated hearts of the snail and slug. 3. 2-Chloroadenosine,
      alpha, beta-methylene ATP and 2-methylthio ATP were inactive at concentrations up
      to 1 mM. 4. Responses were not blocked by any commonly accepted vertebrate
      purinoceptor antagonists, indicating that these purinoceptors are dissimilar to
      vertebrate purinoceptors and cannot be classified according to accepted
      purinoceptor classifications. 5. Electrical field stimulation of the snail heart
      produced frequency-dependent responses: 1-4 Hz produced predominantly excitation,
      8-32 Hz predominantly inhibition. These responses were unaffected by the purines
      up 3 mM.

PMID- 1350965
TI  - Amino acid levels in cerebrospinal fluid of rats after administration of
      pentylenetetrazol.
AB  - 1. We studied the effect of pentylenetetrazol (PTZ)-induced myoclonic jerks and
      generalized clonic-tonic convulsions (GC) on the levels of neurotransmitter amino
      acids in the cisternal CSF of rats. 2. The levels of aspartate, glutamate,
      glycine, and taurine were elevated in the CSF during myoclonic jerks and more
      distinctly immediately after GC. 3. During the recovery period of postictal
      depression seen in EEG (5 min after GC), the CSF levels of transmitter amino
      acids were lower than in the control group. 4. PTZ-induced irritative activity in
      the EEG disappeared in 24 hr but the levels of amino acids remained abnormal. 5.
      Amino acid changes in the CSF following PTZ-induced convulsions might indicate
      that the release of amino acids into the extracellular space is increased before
      and during the propagation of PTZ-induced seizure and decreased during postictal
      depression.

PMID- 1350964
TI  - Production of the cytostatic agent aeroplysinin by the sponge Verongia aerophoba
      in in vitro culture.
AB  - 1. The marine sponge Verongia aerophoba contains two bioactive secondary
      metabolites from tyrosine, (+)-aeroplysinin-1 [3',5'-dibromo-1',2'-dihydroxy-4'-
      methoxycyclohexa-3',5'-dien-1'-yl-methyl-cyanide; abbreviated AP] and
      dibromoverongia-quinol [3',5'-dibromo-1'-hydroxy- 4'-oxocyclohexa-2',5'-dien-1'
      yl-acetamide; abbreviated DV], which display strong cytostatic activity. 2. The
      concentrations causing 50% inhibition of cell growth are 0.47 microM (AP) and
      1.21 microM (DV), resp. 3. Depending on depth regions from which the sponges were
      collected, differences in occurrence of metabolites were observed. 4. AP and DV
      were found to be present in sponges collected at a depth of 5-10 m, whereas only
      DV could be detected in material from deeper regions (20-30 m). 5. AP is present
      only in the surface layers (both the outer and oscular region) of the sponge,
      while in the centre of the sponge only DV is detected. 6. Cubes from sponges,
      collected at a depth of 30 m, were cultivated in seawater in vitro and were found
      to have the capacity (i) to synthesize AP, and (ii) to release this bioactive
      material into the medium under defined conditions. Under optimal conditions
      (light and aeration) 100 g of sponge synthesize and release 13.02 mg of AP during
      a 10-day incubation period. 7. In the dark and without aeration this synthesis
      was prevented. 8. These data show that also under in vitro conditions sponges
      retain the capability of producing bioactive compounds and can be induced to
      produce even substances which they did not secrete in their natural environment.

PMID- 1350966
TI  - Two DNA polymerases from Trypanosoma cruzi: biochemical characterization and
      effects of inhibitors.
AB  - 1. Two DNA polymerases have been partially purified from Trypanosoma cruzi
      epimastigotes by DEAE-cellulose, phosphocellulose, and DNA agarose
      chromatography. 2. Both enzyme activities were characterized by several
      biochemical criteria. 3. They showed different sensitivity to KCl and displayed
      characteristic Mg2+ and Mn2+ requirements, although they exhibited almost
      identical primer-template utilization. 4. The preferred substrates were poly dC
      oligo dG, activated calf thymus DNA, and poly dT-oligo rA. 5. Both enzyme
      fractions are not inhibited by aphidicolin while N-ethylmaleimide and
      phosphonacetic acid inhibited them to different extents. 6. ButylphenyldGTP
      strongly inhibited T. cruzi enzyme fraction I while it had no effect on enzyme
      fraction III. 7. This dGTP analog also inhibited the poly dT-directed
      polymerization of dAMP as described for other mammalian DNA polymerases. Kinetic
      studies indicated that butylphenyldGTP inhibited enzyme fraction I in a non
      competitive fashion.

PMID- 1350967
TI  - Philanthotoxins block glutamatergic transmission in rat hippocampus--I. Reduction
      of high affinity glutamate uptake demonstrated by light microscopy surface
      autoradiography.
AB  - 1. Effects of structural philanthotoxin (PTX) analogues on the high affinity
      uptake of [3H]-L-glutamate by slices of the rat hippocampus were studied using
      light microscopy surface autoradiography. 2. Considering the various effects of
      the PTX-analogues it can be concluded that the presence of an aromatic nucleus in
      the molecule is an important moiety, while the number and distribution of
      positive charges in the polyamine chain seems to be of a still not understood
      importancy.

PMID- 1350968
TI  - Philanthotoxins block glutamatergic transmission in rat hippocampus--II.
      Inhibition of synaptic transmission in the CA1 region.
AB  - 1. Philanthotoxins decrease the amplitude of the population spike (PS), the field
      excitatory postsynaptic potential (f-EPSP), and the presynaptic volley (PV), as
      evoked by Shaffer-collateral-commisural inputs to the CA1 pyramidal cells in the
      rat hippocampus slice. 2. The effects are slow and often not completely
      reversible. 3. Dideaza-philanthotoxin-12 is, in all experiments, the most active
      antagonist showing a very poor recovery. 4. Using a twin pulse the percentual
      decreases of f-EPSP and PV amplitudes are almost identical for the first and
      second response. However, the first PS is much more affected than the second one,
      indicating a possible effect on the inhibiting circuit. 5. Philanthotoxins cause
      a non-competitive inhibition. 6. Besides a possible postsynaptic block and a
      distinct presynaptic effect (preceding paper) a non-postsynaptic effect (on the
      PV) is described.

PMID- 1350969
TI  - Haematological results of vanadium intoxication in Wistar rats.
AB  - 1. Two-month-old rats of the Wistar strain of both sexes received, as sole
      drinking liquid, an aqueous solution of ammonium metavanadate (AMV) of 0.15 mg
      V/cm3 concentration for a period of 4 weeks. 2. A small decrease in the amount of
      food consumed and a significant reduction of the water AMV solution drunk were
      observed, as compared with the food and water taken up by the control group. 3.
      In the peripheral blood a significant decrease in the erythrocyte count and
      haemoglobin level and increased percentage of reticulocytes and
      polychromatophilic erythrocytes were noted. 4. No changes in the activity of
      lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G-6PD) were
      found in the erythrocytes of the animals tested. 5. The increase in the
      neutrophilic granulocyte and lymphocyte count was significant. 6. An inhibitory
      influence of vanadium on the phagocytic activity of granulocytes was observed.

PMID- 1350970
TI  - The localization of FMRFamide in the nervous and somatic tissues of Nereis virens
      and its effects upon the isolated esophagus.
AB  - 1. The tetrapeptide FMRFamide which is present in extracts of Nereis virens was
      localized in various nereid tissues immunohistochemically. 2. Immunoreactive
      FMRFamidergic cells and fibers were found in the supraesophageal (brain) and
      subesophageal ganglia, as well as in the intersegmental ganglia of the ventral
      nerve cord. Immunoreactive fibers were present in the neuropile of, and the
      connectives between, the supraesophageal, subesophageal, and intersegmental
      ganglia. 3. In the periphery immunoreactive FMRFamidergic fibers and a few cell
      bodies were observed in the gut. Sparse fibers were also seen in the body wall,
      parapodia, and cephalic palps. When the antiserum was preabsorbed with FMRFamide,
      no specific immunoreactivity was detected. 4. The esophagus of Nereis, isolated
      and suspended in a tissue bath, responded to FMRFamide with a dose-dependent
      relaxation; threshold was between 30 and 300 nM, and the EC50 was 1.55 +/- 0.60
      microM. Benzoquinonium did not modify this response. 5. Thus, FMRFamide seems to
      be a neurotransmitter in both the central and peripheral nervous system of Nereis
      virens, and may be involved in the control of esophageal motility.

PMID- 1350971
TI  - The utility of spirometry in the diagnosis of reversible airways obstruction.
AB  - Patients with suspected reversible airways obstruction (RAO) sometimes report
      subjective benefit after bronchodilator treatment despite no objective
      spirometric improvement. One possible explanation for this is improvement in
      volume-related or plethysmographic parameters in the absence of spirometric
      improvement. One hundred patients with RAO were assessed before and after inhaled
      bronchodilator to determine the prevalence of improvement by plethysmographic
      parameters in the absence of improvement in spirometric parameters. Spirometry
      alone (FEV1, FVC, and FEF25-75%) identified reversibility of airflow limitation
      in 82 patients. Reversibility was identified by body plethysmography (specific
      conductance [SGaw], thoracic gas volume [TGV], and isovolume maximum expiratory
      flow rates [IVMEF]) in 15 of the remaining patients. The percent predicted FEF25
      75% at baseline was higher in patients who required plethysmography to identify
      reversibility, but could not be used to predict the lack of a spirometric
      response for any individual patient. We conclude that spirometry alone fails to
      identify reversibility in approximately 15 percent of patients, and that most of
      these patients can be identified by additional plethysmographic measurements of
      volume-related parameters. At any one point in time, multiple tests must be used
      together to adequately identify the majority of patients with reversible airways
      obstruction. Improvement in volume-related parameters may explain why some
      patients with RAO improve subjectively with bronchodilators but show no
      spirometric improvement.

PMID- 1350972
TI  - Sudden cardiac death in bronchial asthma, and inhaled beta-adrenergic agonists.

PMID- 1350973
TI  - Infrequent cardiac deaths occur in bronchial asthma.

PMID- 1350974
TI  - Esmolol in the treatment of multifocal atrial tachycardia.
AB  - Multifocal atrial tachycardia (MAT) is a supraventricular tachydysrhythmia
      precipitated by a number of pharmacologic and physiologic disturbances.
      Corrections of these disturbances should take precedence in the treatment of MAT.

PMID- 1350975
TI  - Ibuprofen inhibits adhesion-dependent neutrophil response by a glycoprotein
      unrelated mechanism.
AB  - The anti-inflammatory drug ibuprofen was found to inhibit neutrophil aggregation
      and chemotaxis, triggered by the chemotactic factor N-formyl-methionyl-leucyl
      phenylalanine (FMLP). The drug did not modify the surface expression of the
      glycoprotein CD11b-CD18, required for both aggregation and chemotaxis. Consistent
      with this finding, ibuprofen did not affect the release of lactoferrin from
      secondary granules which contain CD11b-CD18 molecules in their membranes. As the
      drug failed to interfere with the neutrophil oxidant production and primary
      granule release, the results suggest that it acts primarily at the initial steps
      of the neutrophil response during inflammation, i.e. the cell recruitment at
      inflamed tissue sites. Moreover, the data prove that adhesion-dependent
      neutrophil responses required cell processes independent of CD11b-CD18 but
      controlled, at least in part, by ibuprofen-inhibitable pathways.

PMID- 1350976
TI  - Tumor necrosis factor alpha, interleukin 1 and related cytokines in brain
      development: normal and pathological.
AB  - Microglia and astrocytes produce several cytokines including interleukin 1 (IL1)
      and tumor necrosis factor alpha (TNF alpha), which have pleiotropic effects in
      the immune and nervous systems. Recent evidence has come to light that they play
      a role in damage in the central nervous system. This indeed may be the result of
      overproduction of these factors as the consequence of trauma or disease. At lower
      concentrations, however, they may in fact be involved in the normal development
      of the nervous system. A review of brain IL1 and TNF alpha during normal
      development, abnormal development, and pathology is presented here. We have
      speculated as to the association of these cytokines directly and indirectly with
      neural cell migration, proliferation, differentiation, and death.

PMID- 1350977
TI  - Postnatal dietary fat influences mRNAS involved in myelination.
AB  - The synthesis and composition of myelin in the developing mouse central nervous
      system can be influenced by diet. Postnatal maternal fat intake altered nursing
      pup brain and liver fatty acid composition. Peak (day 21) proteolipid protein
      (PLP) and myelin basic protein (MBP) mRNA levels were reduced when pups were
      nursed by mothers fed a fat-free or 5% coconut oil diet. This effect was reversed
      by feeding a corn oil based diet. Oleic acid accounts for about 30% of myelin
      fatty acids. mRNA levels of stearoyl CoA desaturase (SCD), the rate-limiting step
      in oleic acid synthesis, increase in neonatal mouse brain. Postnatal maternal fat
      free feeding reduced day 21 pup brain SCD and LDL receptor, but not
      apolipoprotein (Apo E) E mRNA levels. In contrast to brain, nursing pup hepatic
      SCD mRNA levels were induced, LDL receptor mRNA levels were unaffected and Apo E
      mRNA levels were reduced by postnatal maternal fat-free feeding. Myelin-specific
      mRNA levels are developmentally regulated and influenced by dietary fat. Neonatal
      brain SCD and LDL receptor mRNA levels are also altered by neonatal fat intake.
      The neonatal response to dietary fat is tissue-specific at the mRNA level.

PMID- 1350979
TI  - Maternal tyrosinaemia II: management and successful outcome.
AB  - A 25-year-old woman with tyrosinaemia type II was treated from the 5th week of
      pregnancy with a protein-restricted diet supplemented with a
      tyrosine/phenylalanine-free amino acid mixture. Tyrosine concentrations were
      maintained in the range 100-200 mumol/l by restricting natural protein intake to
      0.16 g/kg per 24 h in early pregnancy, with increases up to 0.38 g/kg per 24 h in
      the last trimester. This treatment maintained plasma phenylalanine concentrations
      in the range 20-40 mumol/l. Maternal weight gain and fetal growth were normal,
      and the mother remained asymptomatic throughout the pregnancy. A normal infant
      was born at term with length, weight and head circumference between the 25-50th
      per centiles.

PMID- 1350978
TI  - Modulation of transcytotic and direct targeting pathways in a polarized thyroid
      cell line.
AB  - Two biosynthetic pathways exist for delivery of membrane proteins to the apical
      surface of epithelial cells, direct transport from the trans-Golgi network (TGN)
      and transcytosis from the basolateral membrane. Different epithelial cells vary
      in the expression of these mechanisms. Two extremes are MDCK cells, that use
      predominantly the direct route and hepatocytes, which deliver all apical proteins
      via the basolateral membrane. To determine how epithelial cells establish a
      particular targeting phenotype, we studied the apical delivery of endogenous
      dipeptidyl peptidase IV (DPPIV) at early and late stages in the development of
      monolayers of a highly polarized epithelial cell line derived from Fischer rat
      thyroid (FRT). In 1 day old monolayers, surface delivery of DPPIV from the TGN
      was unpolarized (50%/50%) but a large basal to apical transcytotic component
      resulted in a polarized apical distribution. In contrast, after 7 days of
      culture, delivery of DPPIV was mainly direct (85%) with no transcytosis of the
      missorted component. A basolateral marker, Ag 35/40 kD, on the other hand, was
      directly targeted (90-98%) at all times. These results indicate that the sorting
      machinery for apical proteins develops independently from the sorting machinery
      for basolateral proteins and that the sorting site relocates progressively from
      the basal membrane to the TGN during development of the epithelium. The transient
      expression of the transcytotic pathway may serve as a salvage pathway for
      missorted apical proteins when the polarized phenotype is being established.

PMID- 1350980
TI  - Induction of high-affinity paf receptor expression during T cell activation.
AB  - Activated human T cells via the CD2 or the CD3 pathways exhibited a higher
      capacity than resting T lymphocytes to incorporate and metabolize [3H]pafacether
      (paf) at 37 degrees C. Resting T lymphocytes lacked specific binding capacity for
      paf, yet high-affinity paf receptors (paf-R) were induced on CD3- or CD2
      dependent activation. This up-regulation in the number of paf-R became apparent
      by day 1 of culture, reached a maximum of about 25,000 sites cell by days 4 to 6
      and subsequently declined. Interestingly, human recombinant interleukin-2 in a
      dose-dependent manner prevented the decrease of high-affinity paf-R expression on
      T cells. By contrast, the receptor affinity was constant throughout the culture
      period. Thus, paf-R at different stages of T cell activation were
      indistinguishable with respect to receptor-ligand interaction, and differed only
      in their number. Together, these data demonstrate that after activation human T
      cells develop membrane high-affinity paf-binding sites. They also suggest for the
      first time that expression of the paf-R are coupled to T cell activation and/or
      differentiation.

PMID- 1350981
TI  - Engagement of class I major histocompatibility complex molecules by cell surface
      CD8 delivers an activation signal.
AB  - Recent evidence has demonstrated that cross-linking class I major
      histocompatibility complex (MHC) molecules on human T cells with monoclonal
      antibodies (mAb) triggers T cell activation. The only known natural ligand for
      MHC class I molecules is CD8. Therefore, the possibility that CD8+ T cells might
      provide activation signals to other T cells by engaging MHC class I molecules was
      examined by culturing CD4+ peripheral blood T cells with Chinese hamster ovary
      cells (CHO) cells that had been transfected with the alpha chain or alpha and
      beta chains of CD8 and assessing interleukin (IL)-2 production. CD4+ T cells did
      not secrete IL-2 when cultured alone, with control or CD8+ CHO cells. In
      contrast, CD4+ T cells produced IL-2 when cultured with CD8+ CHO cells and co
      stimulated with phorbol myristate acetate (PMA) or mAb to CD3 or CD28. PMA
      stimulated substantially less IL-2 when control CHO cells were employed and the
      mAb to CD3 and CD28 did not stimulate IL-2 production in the presence of control
      CHO cells. The co-stimulatory activity of CD8+ CHO cells was completely
      eliminated by mAb to CD8 or MHC class I molecules. The data demonstrate that CD8
      can interact with MHC class I molecules expressed on T cells and deliver a
      costimulatory signal that increases IL-2 production. Thus, engagement of MHC
      class I molecules by its natural ligand, CD8, provides an activation signal to T
      cells. Under some circumstances, such interactions may amplify the responses of T
      cells.

PMID- 1350982
TI  - Changes in expression of CD45R during the development of Th1 and Th2 cell lines.
AB  - Previous studies using anti-CD45R monoclonal antibodies (mAb) have shown that
      normal CD4+ T cells can be separated into virgin and memory cells based on their
      level of expression of CD45R. CD45Rhi (virgin) T cells secrete interleukin (IL)-2
      whereas CD45Rlo (memory) T cells secrete both IL-2 and IL-4. In contrast to these
      results, studies using cultured T cell lines have shown that IL-2-secreting T
      helper cell type 1 (Th1) cells are CD45Rlo and IL-4-secreting Th2 cells are
      CD45Rhi. To resolve this discrepancy, and to determine how the Th1 and Th2 cell
      lines relate to memory CD45Rlo and virgin CD45Rhi CD4+ T cells, we have isolated
      CD45Rlo cells from alloantigen-primed mice and developed allospecific Th1 and Th2
      cell lines. The lymphokines secreted by these lines were then evaluated. Our
      results show that as CD45Rlo T cells develop into in vitro cell lines which
      secrete IL-4, they become CD45Rhi. In contrast, CD45Rlo cells that develop into
      lines which secrete IL-2 maintain their CD45Rlo phenotype. Thus, although both
      Th1 and Th2 cells arise initially from CD45Rlo cells, Th2 cells become CD45Rhi
      during prolonged in vitro culture but, Th1 cells do not.

PMID- 1350983
TI  - Aberrant interleukin (IL)-4 and IL-5 production in vitro by CD4+ helper T cells
      from atopic subjects.
AB  - The cytokine secretion profiles of T cell lines (TCL) specific for purified
      protein derivative (PPD) or streptokinase (SK), contemporarily derived from nine
      atopic and nine nonatopic individuals, were compared. Upon stimulation with
      phorbol myristate acetate (PMA) plus anti-CD3 monoclonal antibody (mAb), all TCL
      from both atopics and nonatopics produced interleukin (IL)-2 and interferon (IFN)
      gamma. The mean IL-2 production by PPD- or SK-specific TCL from both atopics and
      nonatopics was similar, whereas the mean IFN-gamma production by TCL derived from
      atopics was significantly lower. In addition, both PPD- and SK-specific TCL from
      atopics produced detectable amounts of IL-4 and IL-5, whereas the corresponding
      TCL derived from nonatopics did not. A total number of 107 and 99 PPD-specific
      CD4+ T cell clones (TCC) were then derived from TCL of 4 atopic and 4 nonatopic
      donors and assessed for their profile of cytokine production in response to
      stimulation with either PMA plus anti-CD3 mAb or the specific antigen. Under both
      these experimental conditions, virtually all PPD-specific TCC from both atopic
      and nonatopic individuals produced IL-2 and IFN-gamma. In contrast, the great
      majority of PPD-specific TCC derived from nonatopic individuals did not produce
      IL-4 and IL-5, whereas high proportions of PPD-specific TCC derived from atopic
      donors displayed the ability to produce noticeable amounts of IL-4 and IL-5
      besides IL-2 and IFN-gamma. These data indicate that CD4+ T cells from atopic
      individuals are able to produce IL-4 and IL-5 in response to bacterial antigens,
      such as PPD and SK, that usually evoke responses with a restricted type-1 T
      helper (Th1)-like cytokine profile in nonatopic individuals. Aberrant IL-4
      production by Th cells may represent one of the immune alterations responsible
      for enhanced IgE antibody production in atopic people.

PMID- 1350985
TI  - Effects on ingestive behavior in rats of the alpha 1-adrenoceptor agonist
      cirazoline.
AB  - Microinjections of various alpha 1-adrenoceptor agonists including phenylephrine
      and phenylpropanolamine into the paravenricular hypothalamic nucleus (PVN)
      suppress food intake in rats, suggesting that this receptor type might act in
      opposition to previously identified facilatory PVN alpha 2-adrenoceptors in the
      modulation of feeding. In the present experiments, we examine the effects on food
      and water intake of intra-PVN as well as systemic injection of cirazoline, a
      highly potent alpha 1-adrenoceptor agonist. In Experiment 1, intra-PVN
      microinjection of cirazoline (0, 3, 6, 12 and 24 nmol) suppressed food intake
      (ED50 = 23.4 nmol) without significant effects on water intake. In Experiment 2,
      systemic injection of cirazoline (0, 0.05, 0.1, 0.2, 0.4 mg/kg) also markedly
      suppressed food intake (ED50 = 0.05 mg/kg i.p.), with a less potent action on
      water intake (ED50 = 0.22 mg/kg i.p.). The results of this study as well as our
      previous investigations strongly support the notion that alpha 1-adrenoceptors
      within rat PVN act to reliably suppress food intake.

PMID- 1350984
TI  - Sensitivity of T cells to anti-CD3-stimulated suicide is independent of
      functional phenotype.
AB  - We have examined mixed populations and cloned murine CD4+ T cell lines for their
      sensitivity to anti-CD3-stimulated suicide. The sensitivity of CD4+ clones to
      anti-CD3-stimulated suicide is independent of their interleukin-2/interleukin-4
      or interferon-gamma secretion profile or their lytic efficiency in anti-CD3
      redirected lytic assays.

PMID- 1350986
TI  - B-HT 920 stimulates feeding and antagonizes anorexia induced by ACTH and
      immobilisation.
AB  - The influence of immobilisation and i.c.v. injection of ACTH on feeding in rats
      was examined using a new experimental model. An X-maze with alternate open and
      covered arms, each baited with standard laboratory chow was used, where
      individual rats were placed and observed for 5 min. Two essential aspects of the
      behaviour towards food were considered, namely, tasting and feeding. A number of
      parameters were applied to demonstrate the anorectic activity of ACTH and
      immobilisation, in accordance with data obtained using classical procedures for
      feeding analysis. ACTH at the dose used did not modify rat exploratory activity
      and grooming in the X-maze without food pellets. In the same X-maze feeding test,
      B-HT 920, a selective agonist of dopamine D2 receptors and alpha 2-adrenoceptors,
      shown earlier to have anxiolytic- and antidepressive-like properties in rats,
      enhanced appetite and exerted anxiolytic activity when injected i.p. Pretreatment
      with B-HT 920 counteracted the restraint- and ACTH-induced effects. The results
      are discussed in the light of the relation between control of feeding and
      affective disorders. B-HT 920 activity seems to be of particular interest in view
      of its antagonism towards the anorexia elicited by two different agents reputed
      to have in common a key role in the stress-related disturbances of food intake.

PMID- 1350987
TI  - Spontaneous firing level distinguishes the effects of NMDA and non-NMDA receptor
      antagonists on the ganglion cells in the cat retina.
AB  - Different responses of retinal ganglion cells to iontophoretically applied NMDA
      receptor antagonists and non-NMDA receptor antagonists were studied in
      anaesthetized cats. Cells with normal range of spontaneous firing and those with
      abnormally high spontaneous firing levels showed a different response to these
      drugs. Both visually driven and spontaneous firing of cells with 'normal'
      spontaneous firing level were blocked by non-NMDA receptor antagonists, but not
      by NMDA receptor antagonists which often raised spontaneous firing. In contrast,
      the responses of cells with abnormally high spontaneous firing level were blocked
      effectively by NMDA antagonists including MK-801, an NMDA channel blocker, as
      well as by non-NMDA receptor antagonists. The results suggest that under normal
      physiological conditions, NMDA receptors which are not involved in synaptic
      transmission may play a role in reducing the resting discharge level of the
      retinal ganglion cells. NMDA receptors, however, appear to open ion channels in
      response to glutamate input when ganglion cells become abnormally depolarized.

PMID- 1350988
TI  - Possible mechanisms of age-associated reduction of vascular relaxation caused by
      atrial natriuretic peptide.
AB  - We investigated the effect of aging on atrial natriuretic peptide (ANP)-induced
      relaxation and cyclic GMP (cGMP) formation in the rat thoracic aorta. In the
      aorta from young rats (4 weeks old), removal of the endothelium, and treatment
      with the nitric oxide synthesis inhibitor, NG-nitro-L-arginine methyl ester (L
      NAME), the radical scavenger, hemoglobin (Hb), and the soluble guanylate cyclase
      inhibitor, methylene blue (MB), attenuated ANP-induced relaxation and
      considerably reduced ANP-stimulated cGMP formation. With increasing age of the
      rats, the ANP-induced relaxation and cGMP formation in endothelium-intact aorta
      decreased, and Hb, L-NAME and MB no longer inhibited the ANP-induced effects,
      irrespective of whether the endothelium was present or absent. In the arteries
      without endothelium, the age-associated reduction in ANP-induced relaxation was
      less than in arteries with endothelium. Aging also decreased the relaxation
      induced by the soluble guanylate cyclase activator, nitroprusside. Potentiation
      due to the cGMP-phosphodiesterase (cGMP-PDE) inhibitor, M&B 22948, of the ANP
      induced relaxation was greater in aortas from old rats than in those from young
      rats, suggesting that the degradation of cGMP may be accelerated in old rats.
      These results suggest that the relaxant action of ANP on the thoracic aorta from
      young rats is in part modulated by endothelium-derived relaxing factor
      (EDRF/nitric oxide), which in turn activates soluble guanylate cyclase, thus
      elevating the cGMP level. Aging may decrease the ANP-induced relaxation and ANP
      stimulated increase in cGMP level by decreasing the ability of endothelial cells
      to produce EDRF, by decreasing guanylate cyclase activity, and by enhancing cGMP
      PDE activity.

PMID- 1350989
TI  - In vivo labelling of the neuronal dopamine uptake complex in the mouse striatum
      by [3H]GBR 12783.
AB  - Various characteristics of the in vivo striatal binding of [3H]GBR 12783 (1-[2
      (diphenylmethoxy)-ethyl]-4-(3-phenyl-1[3H]-2-propenyl)pipera zine), a specific
      ligand of the neuronal dopamine uptake complex, were determined in mice.
      Increasing doses of the ligand revealed the saturability of the binding at a
      single site with half-maximal saturation at a dose of approximately 7 mumol/kg
      and an apparent maximal number of binding sites (Bmax) of 12.8 pmol/mg protein in
      striatum. Specific binding was prevented by various dopamine uptake blockers,
      pyrovalerone, GBR 13069, GBR 12783, N-[1-2-benzo(b)thiophenyl)cyclohexyl]
      piperidine, cocaine, methylphenidate and was inhibited in a stereoselective
      manner by the enantiomers of nomifensine. Other drugs which are not dopamine
      uptake blockers either did not modify [3H]GBR 12783 binding (the
      diphenylbutylpiperazine derivative flupenthixol) or increased it (the
      diphenylpiperazine derivative flunarizine or the chemically unrelated compounds
      fenfluramine and SKF 525A). A close correlation was found between occupancy of
      the striatal [3H]GBR 12783 binding site and the stimulant locomotor effect of the
      drug. A similar specific striatal binding of [3H]GBR 12783 was evidenced in both
      NMRI and CD1 strains. It was concluded that [3H]GBR 12783 administered in vivo
      provides a measure of the density of dopamine uptake sites in mouse striatum.

PMID- 1350990
TI  - Effects of gentamicin on catecholamine levels in the striatum, hypothalamus,
      adrenal gland and vas deferens.
AB  - The effects of gentamicin, an aminoglycoside antibiotic, on changes in the
      catecholamine levels in the rat striatum, hypothalamus, adrenal medulla and vas
      deferens were studied. When rats were i.v. injected with gentamicin (1.0 mg/kg),
      the catecholamine content of all tissues increased 2-4 h after injection. The
      increases in catecholamine levels induced by gentamicin were about 1.4- to 2.3
      fold those induced by saline. The effect of gentamicin was observed at 0.1 or 0.5
      mg/kg, and was maximal at 2.0 mg/kg. The activity of tyrosine hydroxylase, a rate
      limiting enzyme in catecholamine biosynthesis, was markedly increased in all four
      tissues of rats treated with gentamicin (1.0 mg/kg, 4 h). However, direct
      addition of gentamicin to the tyrosine hydroxylase assay medium did not affect
      tyrosine hydroxylase activity. These data indicate that gentamicin administration
      to rats increases the catecholamine content of both central and peripheral
      catecholamine-containing tissues. The results also suggest that the effect of
      gentamicin is due to an indirect activation of tyrosine hydroxylase.

PMID- 1350991
TI  - A thromboxane A2 synthetase inhibitor retards hypertensive rat diabetic
      nephropathy.
AB  - Spontaneously hypertensive rats (SHR) were injected with streptozotocin (STZ-SHR)
      to induce diabetes. The effect of DP-1904, a thromboxane A2 synthetase inhibitor,
      on diabetic nephropathy was then studied by administering it for 5 months (1 or
      10 mg/kg). DP-1904 did not affect renal 6-keto prostaglandin (PG)F1 alpha
      production in STZ-SHR, but markedly inhibited renal thromboxane (TX) B2
      production, so that the 6-keto PGF1 alpha/TXB2 ratio was significantly increased
      (P less than 0.05). STZ-SHR showed significant uraemia and proteinuria, plus
      increases in urinary gamma-glutamyl-transpeptidase and urinary N-acetyl-beta
      glucosaminidase. DP-1904 significantly decreased (P less than 0.01) the urinary
      changes. STZ-SHR also showed an increase in mesangial periodic acid-Schiff
      positive substance and in relative renal weight, both of which were significantly
      inhibited by DP-1904 (P less than 0.05). Thus, DP-1904 inhibited both TXB2
      production and the progression of renal damage in STZ-SHR.

PMID- 1350993
TI  - Nitric oxide is the endogenous neurotransmitter of bronchodilator nerves in
      humans.
AB  - In human airways, there is a prominent neural bronchodilator mechanism which is
      non-adrenergic. In human tracheal segments, we have demonstrated that this
      response is mediated entirely by nitric oxide (NO), since an inhibitor of NO
      synthesis, L-NG-nitroarginine methyl ester (L-NAME) (10(-4) M) abolishes this
      neural response. Identification of the neurotransmitter of this bronchodilator
      pathway may now make it possible to study its role in physiological control of
      airway calibre and in airway disease.

PMID- 1350992
TI  - Variable alpha 2-adrenoceptor-mediated inhibition of bronchoconstriction and
      peptide release upon activation of pulmonary afferents.
AB  - In the present study, we evaluated the possible regulation by alpha 2-receptor
      agonists (SKF 35886 and UK 14304) of peptide release and functional responses
      upon sensory nerve activation in the guinea-pig lung. The peptide release and
      bronchoconstriction caused by antidromic vagal nerve stimulation (low frequency,
      1 Hz), and a low concentration of capsaicin (10(-8) M) and resiniferatoxin (3 x
      10(-10) M) were attenuated by alpha 2-adrenoceptor agonists. The effects of
      capsaicin and nicotine in high concentrations and high frequency nerve
      stimulation (10 Hz) were influenced to a much smaller extent by alpha 2
      adrenoceptor stimulation. The calcitonin gene-related peptide release evoked by
      bradykinin but not the functional effects was inhibited by alpha 2-adrenoceptor
      activation. It is concluded that alpha 2-adrenoceptor stimulation mainly inhibits
      the release of mediator and/or the bronchoconstriction caused by moderate
      activation of sensory nerves. It is necessary to measure mediator release
      directly to reveal prejunctional effects and not to rely only on indirect
      functional evidence.

PMID- 1350994
TI  - Cardiovascular responses of sinoaortic-denervated rats to intracerebroventricular
      injection of alpha 1- and alpha 2-adrenoceptor agonists.
AB  - The aim of the present work was to analyse the cardiovascular responses induced
      by i.c.v. administration of the alpha 1- and alpha 2-adrenoceptor agonists,
      phenylephrine and clonidine, respectively, in conscious normal and sinoaortic
      denervated rats. Sinoaortic denervation involves changes in central and
      peripheral catecholaminergic pathways. Clonidine (1-10 micrograms) produced a
      dose-dependent rise in blood pressure and a bradycardiac response in sham
      operated animals, whereas in sinoaortic-denervated rats it provoked a brief rise
      in blood pressure followed by a marked fall as well as bradycardia. The responses
      involved mostly activation of central alpha 2-adrenoceptors, but the blood
      pressure responses induced by clonidine in sinoaortic-denervated rats may also
      have involved alpha 1-adrenoceptors. The bradycardia induced by the alpha 2
      agonist in both groups of rats involved preferentially central alpha 2
      adrenoceptors but also partially stimulated alpha 1-adrenoceptors. Phenylephrine,
      at a dose of 10-60 micrograms, induced a rise in blood pressure and a
      bradycardiac response while 90 micrograms produced a biphasic pressure response
      (early transient rise followed by a fall) as well as bradycardia in both sham
      operated and sinoaortic-denervated animals. Phenylephrine activated alpha 1
      adrenoceptors in every case, but the fall in blood pressure and the bradycardia
      also involved alpha 2-adrenoceptors. The responses were significantly higher in
      the sinoaortic-denervated rats than in the sham-operated. Our findings suggest
      that arterial baroreceptor reflexes can modify the effects of alpha-agonists
      initiated in the central nervous system. Sinoaortic denervation preparations
      enable one to unmask the depressor response to clonidine and also demonstrate the
      true magnitude of the phenylephrine response.

PMID- 1350995
TI  - Classification of the beta-adrenoceptor subtype in the rat portal vein: effect of
      altered thyroid hormone levels.
AB  - The potencies of the beta 1-adrenoceptor agonist, noradrenaline, and the beta 2
      adrenoceptor agonist, fenoterol, at beta-adrenoceptors in portal vein were
      examined using preparations isolated from control, methimazole-treated or l
      thyroxine-treated rats. Tissues were preincubated with phenoxybenzamine (1
      mumol/l) to block alpha-adrenoceptors and neuronal and extraneuronal uptake.
      Fenoterol was approximately 400 times more potent than noradrenaline (-log IC50
      7.85 vs. 5.26) in inhibiting the spontaneous contractions of the portal vein. The
      beta 2-adrenoceptor antagonist, ICI 118,551, was approximately 3000 fold more
      potent than the beta 1-adrenoceptor antagonist, atenolol, in blocking the effects
      of fenoterol (pA2 9.32 and 5.88 respectively) and 400 times more potent in
      antagonising noradrenaline (pA2 8.96 vs. 6.23). Treatment of rats with
      methimazole led to decreased myogenic tone, and treatment with thyroxine to
      increased tone. beta-Adrenoceptor binding densities and the relative potencies of
      the agonists and antagonists used were unaffected by methimazole treatment.
      Thyroxine administration was also without effect on the relative potencies of
      these compounds. Our data indicate that although the portal vein is a target
      tissue for thyroxine, as indicated by its influence on myogenic tone, the beta
      adrenoceptor population in this preparation, confirmed to be of the beta 2
      subtype, is unaffected.

PMID- 1350996
TI  - Terguride stimulates locomotor activity at 2 months but not 10 months after 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets.
AB  - The mixed dopamine (DA) agonist/antagonist terguride acts as a DA antagonist on
      normosensitive receptors but shows DA agonistic properties at supersensitive DA
      receptors. Such a compound could offer an alternative to the treatment of
      Parkinson's disease with indirect or direct DA agonists. The present study
      compares the actions of terguride, 4-12 mg/kg i.p., in naive common marmosets
      with its effects in animals rendered parkinsonian by administration of 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2 months or 10 months previously, in
      order to test its antiparkinsonian efficacy. Terguride reduced locomotor activity
      in naive common marmosets, similar to its effects in rodents and in line with the
      DA antagonistic activity of the compound. In marmosets treated with MPTP 2 months
      previously and exhibiting pronounced behavioural motor deficits, terguride
      stimulated locomotor activity, showing DA agonistic properties under these
      conditions. In contrast, the locomotor activity of animals that had recovered
      from MPTP treatment 10 months previously was not altered by terguride. It is
      concluded that terguride has anti-akinetic efficacy in this primate model of
      Parkinson's disease. In addition, terguride offers a unique opportunity to
      differentiate, pharmacologically, the extent of dopaminergic recovery from MPTP
      treatment in this primate species.

PMID- 1350997
TI  - The importance of P and type 1 fimbriae for the persistence of Escherichia coli
      in the human gut.
AB  - The faecal Escherichia coli flora was studied in 89 infants. Each infant was
      followed with a mean of 12 faecal samples (range 5-21) between 0 and 18 months of
      age. All isolates were assayed for P fimbriae and biochemically phenotyped and
      the persistence of each strain (phenotype) in the infant's gut was determined. In
      a subset of strains the occurrence of type 1 fimbriae and adherence to HeLa cells
      was studied. Thirty-one per cent of isolates belonging to strains colonizing for
      longer than 6 months expressed P fimbriae compared to 19% of the isolates from
      strains colonizing 1-6 months or transient strains colonizing less than 1 month.
      Type 1 fimbriae and adherence to HeLa cells occurred similarly often in all
      groups of strains. We conclude that P fimbriae, but not type 1 fimbriae or HeLa
      cell adherence seemed to contribute to the ability of the E. coli strain to
      colonize the human intestine.

PMID- 1350998
TI  - Amino acids and N-acetyl-aspartyl-glutamate as neurotransmitter candidates in the
      monkey retinogeniculate pathways.
AB  - The identity of the neurotransmitter(s) in the mammalian retinogeniculate pathway
      is unclear. To investigate the possibility that some amino acids and certain
      dipeptides, such as N-acetyl-aspartyl-glutamate (NAAG), fulfill this function,
      changes in their concentration were measured in the optic tract, and the
      parvocellular and magnocellular segments of the LGNd of six monkeys (Macaca
      fascicularis), seven days after right optic tractotomy. The LGNd was studied also
      in two additional macaques, three months after occipital lobectomy. Tissue was
      frozen within five minutes of death, regions were dissected with the micropunch
      technique, and substances were analyzed by HPLC. Optic tractotomy induced
      significant, large reductions in NAAG, glutamate and aspartate in the optic tract
      distal to the lesion. Significant decreases in NAAG were also measured in the
      LGNd, and these changes were apparent in both the parvocellular and magnocellular
      segments. A small reduction in glutamate reached significance in the
      parvocellular laminae, and that of aspartate only approached significance in the
      magnocellular division. Occipital lobectomy produced large declines in aspartate
      and glutamate in the LGNd. The results of optic tractotomy support the role of
      NAAG as a neurotransmitter candidate in the monkey retinogeniculate pathways; its
      significant decrease in both geniculate segments suggests that both P- and M-
      retinal axons utilize this substance. Although at times the reductions in
      glutamate or aspartate failed to reach significance, their role cannot be
      excluded. The findings after occipital lobectomy strongly favor these latter
      substances as corticogeniculate and/or geniculocortical transmitters.

PMID- 1350999
TI  - Non-cholinergic effects of acetylcholinesterase in the substantia nigra: a
      possible role for an ATP-sensitive potassium channel.
AB  - Within the substantia nigra acetylcholinesterase has non-cholinergic actions that
      can be demonstrated at both behavioural and cellular levels: the aim of this
      study was, thus, to explore, in the in vitro guinea pig substantia nigra, the
      ionic mechanisms which mediate these non-classical phenomena.
      Acetylcholinesterase had a reversible hyperpolarizing action, via an opening of
      potassium channels, on a selective population of nigral neurons. These neurons
      could be identified by an ability to generate bursts of action potentials and by
      a sensitivity to either amphetamine or to a reduction of glucose in the perfusing
      medium. The acetylcholinesterase-induced hyperpolarization could not be
      attributed to a contaminant in the exogenous solution, since a highly purified
      preparation was even more potent. Furthermore, enzymatic action of any kind could
      be eliminated as boiled acetylcholinesterase was equally efficacious. The effect
      of acetylcholinesterase was not subject to tachyphylaxis and was resistant to
      blockade of potassium channels with tetraethylammonium: since both these
      phenomena are features of the D2 autoreceptor for dopamine within the substantia
      nigra, it seems unlikely that acetylcholinesterase is operating on the same
      target as dendritically released local dopamine. On the other hand, the actions
      of acetylcholinesterase were enhanced by low glucose and blocked by the
      sulfonylurea, tolbutamide. These results strongly suggest that
      acetylcholinesterase can exert a nonenzymatic action and that this action, in the
      substantia nigra, is mediated by an ATP-sensitive potassium channel.

PMID- 1351001
TI  - Selection for class II Mhc heterozygosity by parasites in subterranean mole rats.
AB  - Mhc organization and polymorphism have previously been studied in the four
      chromosomal species of the Spalax ehrenbergi superspecies in Israel,
      serologically, and at the DNA, RFLP and sequence levels of class I and class II
      genes. Here we demonstrate that the observed heterozygosity of Mhc class II genes
      P alpha 1 with 11 alleles, and Q beta, with at least 14 alleles, is positively
      and significantly correlated with infectivities of ectoparasites (gamasid mites)
      and endoparasites (helminths). Mhc heterozygosity is highest in the most infected
      area, which is in the most humid-warm region of the superspecies range, or where
      two zoogeographic regions overlap. We conclude that the evolutionary forces
      responsible for the Mhc class II two-gene polymorphisms include selection for
      increased heterozygosity as a defense strategy against ecto- and endoparasite
      infections.

PMID- 1351002
TI  - The obstetric performance of sickle cell disease patients and homozygous
      hemoglobin C disease patients in Ile-Ife, Nigeria.
AB  - In a 9-year period (1980-1988), 46 delivered hemoglobinopathy patients were
      studied. There was a high incidence of complications during pregnancy. The
      perinatal and maternal mortalities were 13.4% and 9.2% respectively. The
      complications could be minimized by adequate supervision in pregnancy, labor and
      puerperium.

PMID- 1351000
TI  - Evidence that non-NMDA receptors are involved in the excitatory pathway from the
      pedunculopontine region to nigrostriatal dopaminergic neurons.
AB  - Extracellular single-neuron recordings were obtained from electrophysiologically
      identified nigrostriatal neurons in chloral hydrate anesthetized rats, in order
      to test the hypothesis that excitatory amino acid receptors are involved in
      responses of these neurons to electrical stimulation of the pontine region where
      the pedunculopontine nucleus (PPN) is located. The effects of iontophoretic
      application of excitatory amino acids and their antagonists as well as of
      cholinergic antagonists were tested on the fast orthodromic excitation of
      nigrostriatal neurons evoked by stimulation of the PPN region. The N-methyl-D
      aspartate (NMDA) receptor antagonist D-alpha-aminoadipic acid as well as the
      cholinergic receptor antagonists mecamylamine and atropine failed to suppress the
      synaptic excitation of nigral neurons. The NMDA receptor antagonist DL-2-amino-5
      phosphonovalerate exerted a weak depressant action on the synaptic response in a
      few neurons only. On the contrary, the broad spectrum antagonists of excitatory
      amino acid receptors kynurenic acid and gamma-D-glutamyl-amino-methyl-sulphonate
      were found to block simultaneously both the synaptic excitation and the neuronal
      responses to iontophoretic pulses of glutamate while leaving unaffected the
      neuronal responses to local application of acetylcholine or carbachol. The
      competitive antagonist of non-NMDA receptors 6-cyano-2,3-dihydroxy-7-nitro
      quinoxaline suppressed the synaptic excitation at ejection currents which
      antagonized neuronal responses to quisqualate and kainate. These results suggest
      that PPN excitatory fibers synapsing onto pars compacta nigrostriatal neurons
      utilize an excitatory amino acid as a synaptic transmitter acting preferentially
      on non-NMDA receptors.

PMID- 1351003
TI  - Maternal height and the outcome of labor in rural Tanzania.
AB  - The influence of maternal height (standardized for parity and birthweight) on
      obstetrical outcome is studied in 1095 women giving birth in Lugarawa hospital
      and 3869 women delivering in Mbozi hospital, both rural hospitals in the South
      Western Highlands of Tanzania. Short stature was found to increase the need for
      augmentation of labor in primiparae, the need for operative delivery (cesarean
      section/symphyseotomy) in all parity groups and the need for vacuum extraction in
      multiparae. The absence of such an effect of height on perinatal mortality is
      interpreted as the result of obstetric intervention. It is concluded that
      maternal height, which is easy to measure, remains a useful tool to predict
      difficult childbirth and cephalopelvic disproportion.

PMID- 1351004
TI  - Sonographic assessment of the incompetent cervix in pregnancy.
AB  - Ultrasonography (US) was done in 40 women with a history of recurrent
      midtrimester abortion. The results were compared with those of a control group
      who consisted of 53 women with no previous history of abortion and had had at
      least one full term pregnancy with normal vaginal delivery. Mean internal
      cervical os diameters of 16.0 mm and 22.5 mm at 10 and 27 weeks gestation
      respectively were recorded in the cervical incompetent patients while mean values
      of 7.7 mm and 14.5 mm at 13 and 28 weeks gestation were observed in the normal
      control subjects. Full analysis of covariance showed statistically significant
      difference in the internal os diameter between the control group and the cervical
      incompetence cases (t90 = 9.33, P less than 0.001).

PMID- 1351005
TI  - Vaginal microbial flora as a cofactor in the pathogenesis of uterine cervical
      intraepithelial neoplasia.
AB  - The vaginal microbial flora of 106 women with histopathologically confirmed
      cervical intraepithelial neoplasia and 79 women without disease, was evaluated
      for Gardnerella vaginalis, Trichomonas vaginalis, Candida albicans and other
      yeasts. Flora morphology was assessed by gram staining of secretions. Cervical
      cultures were examined for Herpes Simplex virus, Cytomegalovirus and Neisseria
      gonorrhoeae. Chlamydia trachomatis antigens in cervical secretions were detected
      by enzyme immunoassay. Human Papillomavirus was identified by koilocytosis in
      cytologic or histopathologic specimens. Human Papillomavirus infection (P less
      than 0.00001), vaginal infection with Mycoplasma hominis (P = 0.012) and abnormal
      vaginal flora (P = 0.006) were significantly associated with CIN, suggesting that
      CIN may be promoted by vaginal microorganisms in conjunction with human
      papillomavirus cervical infection.

PMID- 1351006
TI  - Health and economic consequences of septic induced abortion.
AB  - Over a period of 7 years, 230 cases of illegally induced abortions complicated by
      sepsis were treated at the University College Hospital, Ibadan, Nigeria. The
      number of terminations complicated by sepsis doubled from 25.4 (between 1981 and
      1985) to 51.0 (between 1986 and 1987) cases per year. Peritonitis was the
      commonest associated complication while maternal mortality was 8.3%. The average
      cost of treatment was US$223.11, while the average monthly earnings was US$45.00.
      Legalization of abortion would have resulted in a saving of US$50,022.28.
      Provision of legal abortion would reduce the incidence of sepsis after
      termination while reproductive health education and information dissemination and
      provision of easily accessible family planning services would greatly reduce the
      number of unwanted pregnancies.

PMID- 1351007
TI  - Cytomegalovirus hepatitis in late pregnancy.
AB  - A case of pregnancy complicated by cytomegalovirus hepatitis is represented. The
      mother had a fulminant disease, but she delivered spontaneously at 31 weeks of
      gestation. The baby was unaffected.

PMID- 1351008
TI  - Growth and rupture of an ovarian endometrioma in pregnancy.
AB  - Pregnancy has long been considered to have beneficial effects on endometriosis.
      We describe a patient who underwent emergency exploratory laparotomy at gestation
      week 35 for rupture of an ovarian endometrioma.

PMID- 1351010
TI  - Maternal oxygen administration and fetal blood flow velocity waveforms in AGA and
      SGA infants.

PMID- 1351009
TI  - Giant broad ligament leiomyoma.
AB  - Giant fibroids are known to arise from the uterus, but occasionally from the
      broad ligament also. A case of giant broad ligament fibroid is reported for its
      rarity, and the diagnostic difficulties it posed are discussed.

PMID- 1351011
TI  - Ectopic pregnancy. ACOG technical bulletin number 150--December 1990 (replaces
      No. 126, March 1989).

PMID- 1351012
TI  - Qualifications and privileges for performing gynecologic laser therapy in the
      lower genital tract. ACOG Committee opinion: Committee on Gynecologic Practice.
      Number 89--December 1990.

PMID- 1351013
TI  - Recommendations on the use of ultrasound and Doppler technology in clinical
      obstetrics and gynecology. FIGO Study Group on the Assessment of New Technology.

PMID- 1351014
TI  - Appropriate technology in maternal and child health. World Health Organization.

PMID- 1351015
TI  - An immunocytochemical study of endocrine cell development in the early fetal
      guinea pig pancreas.
AB  - The presence of insulin, glucagon, pancreatic polypeptide, and somatostatin
      containing cells and their ontogenic changes were investigated
      immunocytochemically in the early fetal pancreas of the guinea pig (Days 25-40).
      In the earliest tissues examined (Day 25 and Day 30) brightly staining glucagon
      cells were the most predominant endocrine cell population, followed by slightly
      fewer and weaker staining pancreatic polypeptide cells. Insulin and somatostatin
      immunoreactive cells were less numerous. At Day 25 all endocrine cells were
      located within the pancreatic tubules where some glucagon cells also coexpressed
      insulin. Similar dual immunoreactivity was present at Day 30. At Day 25 some of
      the pancreatic polypeptide cells also showed coexpression of somatostatin which
      persisted until Days 35-40. At these later stages insulin and somatostatin cells
      were increasingly frequent. Glucagon and pancreatic polypeptide cells were also
      conspicuous. The four endocrine cell types were found either in the pancreatic
      tubules or in the developing islets where they began to acquire an adult-like
      topographic distribution. These studies in the fetal guinea pig show that the
      four islet hormonal cells cytodifferentiate from an early stage. A small
      proportion of endocrine cells coexpress either insulin and glucagon or pancreatic
      polypeptide and somatostatin.

PMID- 1351017
TI  - Comparison of coagulase-negative staphylococci by pulsed-field electrophoresis.
AB  - Five pathogenic strains each of Staphylococcus epidermidis, S. haemolyticus, S.
      lugdunensis and S. schleiferi were analysed by conventional electrophoresis and
      field inversion gel electrophoresis. For these coagulase-negative staphylococci,
      the restriction endonuclease SmaI emerged as the most suitable enzyme for pulsed
      field electrophoresis by providing an adequate number of clearly separated DNA
      fragments. Field inversion gel electrophoresis confirmed the differences among
      strains already discriminated by conventional electrophoresis, and furthermore,
      differentiated strains which had previously appeared identical. Among the species
      that were studied, S. epidermidis showed great genomic diversity with a few
      common bands. On the contrary, S. haemolyticus, S. lugdunensis and S. schleiferi
      showed less diversity. Although these minor variations may be epidemiologically
      significant, this question has to be investigated on a larger number of strains.

PMID- 1351016
TI  - Presence and subcellular localization of tyrosine aminotransferase and p
      hydroxyphenyllactate dehydrogenase in epimastigotes of Trypanosoma cruzi.
AB  - Cell-free extracts of epimastigotes of Trypanosoma cruzi contain tyrosine
      aminotransferase (TAT) and p-hydroxyphenyllactate dehydrogenase (pHPLDH). The TAT
      activity could be separated from aspartate aminotransferase (ASAT) by
      polyacrylamide gel electrophoresis or DEAE-cellulose chromatography; the latter
      procedure also allowed complete separation of pHPLDH. The subcellular
      localization of both T. cruzi enzymes, as determined by digitonin extraction,
      subcellular fractionation by differential centrifugation, and isopycnic
      ultracentrifugation in sucrose gradients, was mainly cytosolic, with low
      mitochondrial activities.

PMID- 1351018
TI  - Structures of the genes encoding the alpha and beta subunits of the Neurospora
      crassa mitochondrial ATP synthase.
AB  - We have isolated and sequenced cDNA and genomic clones encoding the alpha and
      beta subunits of the Neurospora crassa ATP synthase. The genes are not linked to
      each other: atp-1(alpha) maps to either linkage group I or V, and atp-2(beta)
      lies on linkage group II. The two genes resemble each other in having a large
      number of introns, five in atp-1 and seven in atp-2, mostly positioned near their
      5' ends and varying in length from 60-332 bp. The coding regions of both genes
      have a high G+C content (59%) and use a low number of codons, 46 (atp-1) and 44
      (atp-2), a feature associated with highly expressed genes. Northern-blot analysis
      shows both genes are expressed at high levels during mycelial growth. Comparison
      of the exon-intron structures of the beta-subunit-encoding gene with those from
      human and tobacco showed a similar number of introns, several closely positioned,
      but no exact conservation in position, size or sequence of introns.

PMID- 1351019
TI  - Homeobox-containing genes in the newt are organized in clusters similar to other
      vertebrates.
AB  - In vertebrates, the majority of homeobox (HBox) genes are found in four clusters
      and this structural organization is believed to be of functional importance. Many
      HBox genes sustain their expression in the appendages of the adult newt. To
      further understand their regulation, the genomic loci of four newt HBox genes
      (two from the human HBox (HOX)-2 complex and two from the HOX-3 complex) were
      analysed and compared with homologous loci in other vertebrates. Notophthalmus
      viridescens HBox (NvHBox) genes were selected from a lambda EMBL3 library and
      analysed by restriction mapping and nucleotide (nt) sequencing. The nt sequences
      of the NvHBox genes have a very high degree of homology (more than 90%) with the
      human and mouse HBox genes, HOX-3.3, HOX-3.4, HOX-2.7 and HOX-2.8. The sequences
      flanking the HBox are also very homologous to their human and mouse counterparts.
      Moreover, the size of the DNA spacer separating NvHBox-3.3 from NvHBox-3.4, and
      NvHBox-2.7 from NvHBox-2.8 in the newt is similar in the homologous regions of
      the mouse and human, despite there being a C value ten times greater in the newt
      genome. Finally, three of these NvHBox genes are expressed in the limbs of the
      adult newt.

PMID- 1351020
TI  - Expression of a single lignin peroxidase-encoding gene in Phanerochaete
      chrysosporium strain ME446.
AB  - A previously described linked set of lignin peroxidase-encoding genes (Lpo) from
      Phanerochaete chrysosporium (P.c.) ME446 is not expressed under standard growth
      conditions for ligninolytic activity. However, a single unlinked Lpo gene, not
      previously described in P.c. strain ME446, is expressed. The transcription start
      points of this gene are mapped and the gene is assigned to a genetic linkage
      group by the use of restriction-site polymorphism segregation analysis. No
      transcripts from Lpo-related genes, including that normally expressed in ME446,
      could be detected within RNA extracted from three nonligninolytic mutant strains,
      but a hyper-ligninolytic strain showed an increased level of Lpo expression. This
      increase is due to expression of additional Lpo genes, rather than to an
      increased level of transcription from the normally expressed sequence.

PMID- 1351022
TI  - 1991 report concerning recommendations of the DNA Commission of the International
      Society for Forensic Haemogenetics relating to the use of DNA polymorphisms.

PMID- 1351021
TI  - Sequence of the bovine CD18-encoding cDNA: comparison with the human and murine
      glycoproteins.
AB  - The bovine cDNA (CD18) encoding CD18, a cell-surface glycoprotein involved in
      multiple leukocyte functions, was sequenced and compared with the human and
      murine sequences. Portions of the 5'- and 3'-untranslated regions of the
      nucleotide sequences are conserved among the three species, including a 3' A+T
      rich region believed to regulate mRNA stability and translational efficiency. The
      2833-bp bovine sequence coded for a protein of 769 amino acids (aa). Overall, the
      deduced aa sequences were greater than 80% identical among the three species. The
      aa 96-389 and those in the cytoplasmic domain were very highly conserved with
      approx. 95% aa identity. All Cys residues and potential Asn-glycosylation sites
      present in the bovine sequence were also present in the human and murine
      sequences. The aa identity was also found in those regions where mutations were
      found to cause the genetic disease, leukocyte adhesion deficiency. These data
      identify functionally important regions of the CD18 mRNA and protein.

PMID- 1351023
TI  - Statistical analysis of the measurement errors in the determination of fragment
      length in DNA-RFLP analysis.
AB  - DNA from human whole blood samples was digested with the restriction enzyme HinfI
      and RFLP analysis performed using the single locus probes MS1, MS31, MS43a and
      YNH24. The intergel variation of 3291 duplicate measurements of fragment lengths
      in terms of basepairs was investigated. The difference between two measurements
      of the same fragment on different gels increased approximately exponentially with
      increasing fragment length. After transformation of the fragment length into a
      normalized migration distance it was found that the difference between two
      transformed measurements was normally distributed with a S.D. (0.70 mm) which was
      independent of the fragment length. The errors of band 1 and band 2 on the same
      lane were correlated (r2 = 0.8). It is useful in the calculation of frequencies
      and in retrieval procedures and also in the calculation of likelihood ratios to
      be able to use a S.D. which is independent of the fragment length.

PMID- 1351024
TI  - [Does HIV stimulate T-lymphocytes to "suicide"?].

PMID- 1351025
TI  - [Prevention of migraine using bisoprolol. Results of a double-blind study versus
      metoprolol].
AB  - AIMS: Comparison of bisoprolol, a beta-1 selective beta blocker with no intrinsic
      sympathomimetic activity (ISA) and metoprolol, which numerous studies have shown
      to be an effective migraine prophylactic. STUDY DESIGN: Multicentric, cross-over
      study. PATIENTS: 125 patients suffering at least from 3 attacks of classic or
      common migraine a month for at least two years. TREATMENT: Bisoprolol 5 mg given
      once a day, or metoprolol 50 mg given twice a day, for two periods of 12 weeks.
      RESULTS: 125 patients were admitted to the 4-week run-in phase. A comparison of
      the main target: frequency of migraine attacks was thus carried out in 78
      patients (f. = 63, m. = 15). Both substances reduced the average frequency of
      migraine per 28-day period by about 50%. There was no statistically significant
      difference between the two beta-blockers (p greater than 0.05). CONCLUSIONS: The
      results of the study show that 5 mg of bisoprolol and 100 mg of metoprolol a day
      have comparable efficacy for migraine prophylaxis, and show comparable
      tolerability.

PMID- 1351026
TI  - [Interactions of theophylline and H2 receptor antagonists. Interaction modes-
      clinical relevance].
AB  - Basic considerations: peptic ulcers and obstructive diseases occur jointly, since
      cigarette smoking is an important causal factor in both diseases. Major topics:
      The interaction possibilities of theophylline and H2-receptor antagonists on the
      various levels from absorption to elimination of the two drugs are discussed,
      with emphasis being attached to oxidative breakdown in the liver. The clinical
      relevance of such interactions arises from the limited therapeutic spectrum of
      theophylline. CONCLUSIONS: Treatment with both drugs should take account of the
      varying tendency of the individual H2-receptor antagonists to interact.

PMID- 1351027
TI  - [Neuroleptic therapy and suicide--review of the literature and personal results].
AB  - The majority of schizophrenic patients receive neuroleptics (NL) and a relatively
      high number of them commit suicide. Is there a relationship between the two
      variables? Long-term observations failed to demonstrate an interdependence
      between a large-scale introduction of NL in the therapeutic practice and suicide
      rates. There is a relationship between depression and suicide and depressive
      syndroms are frequent in schizophrenic patients. Depressions due to an exclusive
      use of NL probably do occur, but quite seldom so. Also, possible relationships
      between other NL side effects (akathisia, dysphoric reaction to NL) and suicidal
      behavior are not sufficiently supported by the clinical data. Direct comparisons
      in controlled studies (the own study included) between NL therapy of suicide and
      control subjects yielded no consistent results. Suicide promoting effect of NL
      cannot be postulated on the basis of the available data, however, it also cannot
      be fully excluded in individual cases.

PMID- 1351028
TI  - [Clinical symptoms and therapy of status epilepticus].
AB  - The term "status epilepticus" was first coined in 1824 by Calmeil as this
      condition had such a poor prognosis. Although still commonly misused today, from
      the beginning this term actually included all kinds of epileptic seizures, since
      there are as many types of status epileptici as there are seizure types. Status
      epileptici are usually triggered by a combination of factors including sleep
      deprivation, alcohol withdrawal, failure to take medication regularly and fever.
      In status epilepticus epileptic seizures and EEG discharges initially appear to
      be no different from isolated seizures. The longer the status epilepticus
      continues, however, the more atypical the seizures and EEG discharges become.
      Usually status epilepticus ends gradually. Irreversible damage or fatalities may
      occur especially in infants or under certain conditions (e.g. long status
      duration, protracted interval between seizure onset and medical treatment and
      symptomatic etiology). In most cases benzodiazepines and diphenylhydantoine are
      the preferred drugs used for treatment.

PMID- 1351029
TI  - Effects of the right to refuse medication in an emergency psychiatric service.

PMID- 1351031
TI  - Huntington disease in Finland: a molecular and genealogical study.
AB  - Huntington disease (HD) is found at exceptionally low frequency in the Finnish
      population. In this population, linkage disequilibrium was earlier established
      with markers from the D4S10 and D4S43 loci. We now report a continuation to the
      restriction fragment length polymorphism haplotype analysis, in combination with
      a genealogical study of all the Finnish HD families. When the HD pedigrees were
      systematically traced to the 18th century, only one consanguinity was found, and
      a high percentage (28%) of the families had foreign ancestors. The majority of
      the Finnish ancestors were localized to border regions or trade centers of the
      country following the old postal routes. The observed high risk haplotypes formed
      with markers from the D4S10 and D4S43 loci were evenly distributed among the HD
      families in different geographical locations. Consequently, the HD gene(s) has
      most probably arrived in Finland on several occasions via foreign immigrants
      during the last few centuries.

PMID- 1351030
TI  - Phenotype of disease in three patients with identical mutations in methylmalonyl
      CoA mutase.
AB  - We have previously identified a mutation in the gene for methylmalonyl CoA mutase
      in a patient with the mut- phenotype of methylmalonic aciduria. This mutation
      (G717V) interferes with the binding of the deoxyadenosylcobalamin cofactor to the
      apoenzyme producing a mutant holoenzyme that is defective, but not completely
      inactive, in vitro. This report describes the clinical phenotype associated with
      this mutation in the original patient and two additional patients who are
      homozygous for this allele. All three patients presented in the first years of
      life with multiple episodes of life-threatening organic acidosis and
      hyperammonemia. None had evidence of disease in the perinatal period, and all
      three have low-normal intelligence. These three children exhibit a distinctive
      phenotype of disease that is intermediate between the fulminant and benign forms
      of methylmalonic aciduria. These data suggest that this phenotype is the specific
      consequence of the G717V mutation, and that the degree of residual enzyme
      activity associated with the G717V mutation is close to the threshold required in
      vivo for maintaining metabolic homeostasis.

PMID- 1351032
TI  - Genetics of neurofibromatosis 1 in Japan: mutation rate and paternal age effect.
AB  - We have performed formal genetic studies on 26 patients (14 males, 12 females)
      with neurofibromatosis 1 (von Recklinghausen's disease, NF1) in Japan. Family
      studies of 74 members of 18 kindreds revealed that 50% of the cases were caused
      by a new mutation; the mutation rate was assumed to be 7.3-10.5 x 10(-5). A
      tendency of paternal age effect, which was not accounted for by the maternal age
      effect, was observed, but live-birth order had no significant effect. Genetic
      linkage of neurofibromatosis 1 to the NF1 gene or the genetic marker in the
      pericentric region of chromosome 17 was established in 3 informative families.

PMID- 1351033
TI  - Linkage disequilibrium detected between myotonic dystrophy and the anonymous
      marker D19S63 in the Spanish population.
AB  - We used the following polymorphic markers: APOC2 (BanI, BglI, TaqI), CKMM (NcoI,
      TaqI), and D19S63 (PstI) to haplotype 33 Spanish myotonic dystrophy (DM)
      families. We analysed the allele and haplotype frequencies of our sample, and the
      possible association of alleles or haplotypes with the disease. We found a slight
      linkage disequilibrium between APOC2 (BanI) and DM, but no disequilibrium when
      using all other APOC2 and CKMM RFLPs; this agrees with data previously reported.
      In addition, we found a very strong linkage disequilibrium when using D19S63
      (PstI), the + allele being associated with the DM locus. This disequilibrium in
      the Spanish population indicates that D19S63 is very close to the DM locus.

PMID- 1351034
TI  - Loss of normal allele of the APC gene in an adrenocortical carcinoma from a
      patient with familial adenomatous polyposis.
AB  - Endocrine neoplasms have been reported occasionally in patients with familial
      adenomatous polyposis (FAP). An adrenocorotical carcinoma was studied in a
      patient with a family history of FAP. Loss of heterozygosity (LOH) in the region
      close to the adenomatous polyposis coli (APC) gene was detected in this
      carcinoma, and evidence was obtained that there was a loss of the normal allele
      of the APC gene. This is the first demonstration of LOH at the APC locus in
      adrenocortical tumors. The present results and our previous data on LOH in a
      recurring desmoid tumor suggest that the heterozygous mutant/wild-type condition
      of the APC gene may give rise to benign tumors, and that functional loss of this
      gene leads to development of tumors not only in the colon but also in other
      various parts of the body in FAP patients.

PMID- 1351035
TI  - RNA analysis from newborn screening dried blood specimens.
AB  - We have previously demonstrated that DNA can be extracted from the dried blood
      specimen of the type used for newborn screening. The technique presented here
      allows us to extract RNA from newborn screening specimens for cDNA synthesis by
      reverse transcriptase and amplification by the polymerase chain reaction (PCR).
      Products of the PCR reaction are then analyzed by restriction enzymes. This
      method successfully distinguishes beta A and beta S transcripts in unaffected
      (AA), carrier (AS), and affected (SS) individuals. The value of this approach for
      identification of a compound heterozygous patient with S/beta-thalassemia, using
      the original newborn screening specimen, is also demonstrated. This work shows
      that mRNA is stable in dried blood specimens and that analysis of the mRNA
      phenotype can be a useful adjunct in the application of molecular genetic
      technology to newborn screening.

PMID- 1351036
TI  - The molecular basis of beta-thalassemia in Turkey.
AB  - By using oligonucleotide hybridization, restriction endonuclease analysis and
      direct sequencing of amplified genomic DNA, we have been able to characterize 18
      different mutations in the beta-globin genes of 161 beta-thalassemia homozygotes
      and 107 beta-thalassemia heterozygotes from Turkey (429 beta-thalassemia
      chromosomes). Previous studies dealing with beta-thalassemia in Mediterranean
      countries have shown that, in most Mediterranean populations, only a few
      mutations are prevalent. In contrast, beta-thalassemia in Turkey does not seem to
      be associated with a few predominant mutations. The six most frequent alleles,
      IVS-I-110 (G----A), IVS-I-6(T----C), FSC-8 (-AA), IVS-I-1(G----A), -30(T----A)
      and FSC-5 (-CT), account for only 69.3% of the disease genes; indeed, all 26
      mutations assayed represent 85.8% of the disease genes, confirming the
      considerable molecular heterogeneity of beta-thalassemia among Turks, and
      indicating the possible presence of rare, previously undefined, mutations in the
      population. Two mutations observed in this study, IVS-I-116 (T----G) and Cd44(
      C), have not been reported in the Turkish population to date. Since preventive
      medical services, such as genetic counseling and prenatal diagnosis, are greatly
      improved by detailed knowledge of the molecular pathology of beta-thalassemia, we
      strongly believe that the presented data will facilitate the intended
      establishment of a prenatal diagnosis center, based on DNA analysis, in Turkey.

PMID- 1351039
TI  - Transthyretin Pro55, a variant associated with early-onset, aggressive, diffuse
      amyloidosis with cardiac and neurologic involvement.
AB  - Mutations in the protein transthyretin cause amyloidosis involving the heart,
      peripheral nerves, and other organs. A family from West Virginia developed an
      unusually aggressive form of widespread transthyretin amyloidosis. Single-strand
      conformation polymorphism analysis revealed a variant in the transthyretin gene,
      which was found on sequencing to be a T----C transversion at position 2 of codon
      55, corresponding to a Leu----Pro substitution. The variant sequence was
      confirmed by restriction analysis and polymerase chain reaction (PCR)-primer
      introduced restriction analysis.

PMID- 1351038
TI  - Beta-thalassemia major resulting from a compound heterozygosity for the beta
      globin gene mutation: further evidence for multiple origin and migration of the
      thalassemia gene.
AB  - We describe in a Japanese family beta zero-thalassemia resulting from a compound
      heterozygosity for a beta-globin gene mutation. One mutation is a C-to-T
      transition at IVS-2 nucleotide position 654 on the background of Mediterranean
      haplotype IX. Another mutation is a G-to-A transition at IVS-2 nucleotide
      position 1, associated with a novel haplotype XI. The occurrence of these
      mutations on various chromosomal backgrounds provides strong evidence for an
      interplay of gene migration, interallelic gene conversion, and multiple origins
      of the same mutation.

PMID- 1351040
TI  - A rare FokI RFLP in the human dopamine D2 receptor gene (DRD2).
AB  - A new biallelic polymorphism for FokI restriction enzyme due to C----T transition
      in the fourth intron of human DRD2 is described. It must be a usefull marker of
      this candidate gene for several mental disorders.

PMID- 1351037
TI  - Human alpha-globin gene expression is silenced by terminal truncation of
      chromosome 16p beginning immediately 3' of the zeta-globin gene.
AB  - The high level expression of the human alpha-globin genes in erythroid tissue
      appears to require a set of DNaseI hypersensitive sites located upstream of the
      human alpha-globin gene cluster. These sequences, termed the locus control region
      (LCR), include two erythroid specific and a number of less restricted DNaseI
      hypersensitive sites. In this report we describe an individual with alpha
      thalassemia associated with a truncation of the short arm of chromosome 16 that
      removes the LCR region and inactivates the adjacent intact alpha-globin genes.
      This genetic study supports the critical role of the LCR in the transcriptional
      activation of the human alpha-globin gene cluster and substantiates the
      importance of LCR deletions in the etiology of alpha-thalassemia.

PMID- 1351041
TI  - A polymorphic PstI site in intron 2 of the human apolipoprotein C-II gene
      detected by polymerase chain reaction.

PMID- 1351042
TI  - Method for storing Lagenidium (Oomycetes: Lagenidiales).
AB  - Techniques for storing the mosquito pathogenic fungus, Lagenidium, were
      evaluated. A technique, which involves storage of fungal mycelia in sterile
      distilled water of pH 6-7 with 0.0025 M glucose at 30-35 degrees C, was found to
      be useful. When stored in this manner the fungus retained it's larvicidal
      activity for 190 days.

PMID- 1351043
TI  - Congenital adrenal hyperplasia and complete masculinization masquarading as
      sexual precocity and cryptorchidism.

PMID- 1351044
TI  - An attempt to define sets of cooperating genetic alterations in human breast
      cancer.
AB  - The extent and the variation of losses of genetic material were examined in a
      series of 191 human breast cancers by means of a set of 18 polymorphic DNA
      probes, specific of 7 chromosomal arms (1p, 1q, 3p, 11p, 13q, 17p and 18q) known
      to be frequently affected by allele losses. Frequencies of losses of
      heterozygosity ranged from a low of 3.5% (chromosome 13q) to a high of 27%
      (chromosome 3p). The number of sites involved in breast cancer added to the
      frequent occurrence of concomitant losses at several chromosomal arms within the
      same tumor suggest cooperative effects of these LOHs. We were therefore
      interested in assessing the existence of preferential associations between sets
      of LOHs in our panel of tumors. Statistically significant associations were found
      between LOHs at chromosomes 1p and 17p, and between LOHs at chromosomes 11p and
      17p. Furthermore, since all the tumors presently studied had previously been
      analyzed for proto-oncogene amplification at 5 distinct chromosomal sites, we
      tested for associations between LOH and DNA amplification. Such associations were
      indeed observed as exemplified by the correlations observed between the LOH at
      11p and amplification of the erbB2 gene and LOH at 17p and the amplification of
      the flg gene. The only correlation with clinico-pathological parameters that
      could be observed linked the occurrence of LOHs on 11p with recurrent breast
      cancer (p = 0.015). Sets of several LOHs or LOHs and gene amplifications could
      not be significantly related to any marker of tumor aggressiveness.

PMID- 1351045
TI  - Frequent expression of the tumor antigen CAK1 in squamous-cell carcinomas.
AB  - K1 is a murine monoclonal antibody (MAb) derived from a hybridoma generated by
      the fusion of splenocytes of BALB/c mice immunized with a human ovarian tumor
      cell line, OVCAR-3. This antibody reacts strongly with epithelial ovarian tumors
      and mesotheliomas. The antigen recognized by MAb K1, designated CAK1, has
      recently been characterized as a 40-kDa protein probably anchored to the cell
      surface by glycosyl-phosphatidylinositol. Using immunoperoxidase histochemical
      methods, we examined 37 squamous-cell carcinoma (SqCC) samples from cervix, lung,
      esophagus and other origins, and 12 normal squamous epithelia of the cervix and
      esophagus for their reactivity with MAb K1. Of the SqCC specimens, 81% showed K1
      reactivity with variable intensity, but none of 12 normal tissue samples of
      squamous epithelia did so. Two patterns of CAK1 expression in tumor samples were
      found, i.e., a heterogeneous pattern with strong intensity, and a homogeneous
      pattern with weak intensity. Three carcinomas in situ of the larynx, vulva and
      esophagus were moderately positive with K1, suggesting that CAK1 antigen may
      occur in the early stage of carcinogenesis of SqCC. The expression of CAK1 was
      also compared with expression of CA125, HER-2/neu, p53 and P-glycoprotein, and
      MAb K1 was found to react most consistently with SqCC. Since K1 reacts with a
      majority of cervical and esophageal carcinomas but has no detectable reactivity
      in normal epithelia of the cervix uteri and esophagus, MAb K1 could be of value
      as a reagent to help distinguish between normal and neoplastic cells on sections
      as well as in cytological samples.

PMID- 1351046
TI  - Heatstroke and hyperthermias.
AB  - We describe the pathogenesis and the typical clinical and laboratory features of
      the hyperthermia syndromes that may develop during neuroleptic drug treatment,
      environmental exposure or following the use of inhalational anesthetics. Since
      the features are similar and confusion is possible we emphasize the need for
      prompt diagnosis so that appropriate treatment, can be started without delay.
      Hyperthermic reactions have common pathophysiological mechanisms and they may be
      seen as an abnormal individual response to organic and functional stressors.

PMID- 1351047
TI  - Levamisole augments roxatidine's immune modulatory effects in the graft-versus
      host reaction (GVHR).
AB  - Levamisole is known to have anti-anergic properties in immune compromised, but no
      or only marginal effects in immunologically competent subjects. In this study the
      possibility that levamisole would act as an 'immunoadjuvant' with roxatidine, a
      histamine H2 receptor blocker, is explored in healthy animals. Sixteen female,
      inbred Sprague-Dawley rats acted as lymphocyte donors and were treated for 8 days
      with either a roxatidine-levamisole combination, or levamisole alone, or
      roxatidine alone or placebo. Five randomly bred guinea pigs and eight inbred BD
      IX rats acted as lymphocyte acceptors. The in vivo effects of the four treatment
      modalities on transferred lymphocytes were expressed as the sizes of the
      allogeneic and xenogeneic graft-versus-host reactions as well as the
      radioactivity in each AGVHR. The combination of levamisole and roxatidine
      significantly augmented the cell mediated immune response in vivo and resulted in
      the most reactive lymphocytes as indicated by the AGVHR's and XGVHR's. These
      cells mediated reactions with significantly larger wheals as well as more
      lymphocyte proliferation in each reaction site than those caused by either
      levamisole or placebo treatment.

PMID- 1351048
TI  - N-[9H-(2,7-dimethylfluorenyl-9-methoxy)carbonyl]-L-leucine, NPC 15669, prevents
      neutrophil adherence to endothelium and inhibits CD11b/CD18 upregulation.
AB  - NPC 15669, a member of a new class of antiinflammatory agents termed leumedins,
      blocks inflammation in several animal models, including contact dermatitis and
      Arthus reaction, by inhibiting recruitment of neutrophils and lymphocytes into
      inflammatory lesions. These compounds do not block lipid metabolic enzymes, nor
      do they antagonize receptors for various chemoattractants, including LTB4, PAF,
      C5a, and fMLP. This report demonstrates that in vitro, pretreatment of stimulated
      neutrophils with NPC 15669 results in the dose-dependent inhibition of adherence
      to cultured human umbilical vein endothelial cells or to the protein substrate
      keyhole limpet hemocyanin. Adherence of HL-60 cells (a promyelocytic line) is
      unaffected when stimulated endothelial cells are pretreated with NPC 15669. Flow
      cytometric analysis of adhesion molecules expressed on neutrophils revealed that
      pretreatment of neutrophils with NPC 15669 prior to activation inhibits the
      increase in expression of the CD11b and CD18 adhesion molecule subunits. We
      conclude that (1) NPC 15669 acts on neutrophils to block activation-induced
      adherence, and (2) NPC 15669 inhibits the upregulation of the CD11b/CD18 (Mac-1)
      adhesion receptor.

PMID- 1351050
TI  - Cefpirome: a novel extended spectrum cephalosporin. Proceedings of the 17th
      International Congress of Chemotherapy. Berlin, Germany, 23-28 June 1991.

PMID- 1351051
TI  - 1991 Oxford Conference: fifth meeting on control of breathing and its modeling
      perspective.

PMID- 1351052
TI  - Neurogenic inflammation and asthma.
AB  - The release of neurotransmitters may exacerbate the inflammatory response. Such
      neurogenic inflammation has been documented in a number of inflammatory diseases.
      Neurogenic inflammation due to release of neuropeptides from sensory nerves has
      been demonstrated in airways of several species, particularly rodents, and may
      contribute to the inflammatory response in asthmatic airways. Tachykinins
      (substance P and neurokinin A) released from airway sensory nerves may cause
      bronchoconstriction, vasodilatation, plasma exudation, and mucus secretion,
      whereas another sensory neuropeptide, calcitonin generelated peptide, may
      contribute to hyperemia of inflammation. Airway epithelial damage in asthma
      exposes sensory nerves which may become sensitized by inflammatory products
      (including prostaglandins and cytokines) so that neuropeptides are released via a
      local reflex trigger such as bradykinin, resulting in exaggerated inflammation.
      The effects of tachykinins may be amplified further by loss of the major
      degrading enzyme, neutral endopeptidase, from epithelial cells. Direct evidence
      for neurogenic inflammation in asthma is still awaited, however. Several
      strategies for reducing neurogenic inflammation are possible, particularly
      inhibition of neuropeptide release from sensory nerves by stimulating
      prejunctional receptors such as mu-opioid receptors.

PMID- 1351049
TI  - Effects of caudal elevation on testicular function in rats. Separation of effects
      on spermatogenesis and steroidogenesis.
AB  - A variety of biologic processes are perturbed when exposed to microgravity (space
      flight) for more than 7 days, including testicular function. Suspension of rats
      in a special harness (caudal elevation) to induce thoracic pooling of blood
      fluids and remove the support function of the hind limbs is used to mimic, on
      earth, the effects of microgravity encountered during space flight. Typically,
      this induces cryptorchidism in male rats. Three experiments were conducted to
      differentiate the effects of caudal elevation (30 degrees angle) and anatomic
      location of testes on spermatogenesis and steroidogenesis. Rats were subjected to
      caudal elevation for 7 days using either a tail harness (experiments 1 and 2) or
      a whole-body harness (experiment 3). Testes of rats fell into the abdominal
      cavity when a tail harness was used, but ligation of the inguinal canal prevented
      this repositioning. For rats with abdominal testes, testicular weight was reduced
      (P less than 0.05) and histology of testes was abnormal; the number of spermatids
      per gram parenchyma was lower (P less than 0.05) in tail-suspended rats compared
      with control rats. In contrast, spermatogenesis was not affected by caudal
      elevation in most rats in which the inguinal canal was ligated or in rats
      elevated by whole-body harness. Concentrations of testosterone in serum and
      testicular interstitial fluid were lower (P less than 0.05) in suspended rats,
      regardless of the method used for caudal elevation or anatomic location of
      testes. Concentrations of luteinizing hormone in serum were elevated (P less than
      0.05) in rats with intra-abdominal testes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351053
TI  - The effect of repeat action albuterol sulfate (Proventil Repetabs) in nocturnal
      symptoms of asthma.
AB  - At four medical centers, 98 patients with stable asthma, histories of nighttime
      awakening at least three times weekly and nighttime declines of pulmonary
      function of at least 15%, who were not taking oral adrenergic agonists, were
      randomly treated with either oral repeat-action albuterol sulfate (Proventil
      Repetabs), 4 mg in the morning and 4-16 mg at bedtime, or a placebo for 2 weeks.
      All patients were required to have nocturnal symptoms of asthma, with prior use
      of bronchodilators other than oral adrenergic agonists to be eligible for the
      study. The patients maintained a diary of asthma symptom scores and recorded peak
      flow rates at home at bedtime and in the morning. They had spirometry (FEV1, FVC,
      and PEFR) after a 1-week baseline stabilization period, and after 1 and 2 weeks
      of double-blind oral therapy as noted above. Efficacy was evaluated by changes in
      the bedtime and morning peak flow rates, changes in the number of nighttime
      awakenings, results of office spirometry testing, and by physician and patient
      global evaluations of response to therapy. Of the 98 patients in the study, 47
      received oral albuterol, and 51 received placebo. The patients on albuterol had a
      statistically significant reduction in the number of nighttime awakenings (p less
      than or equal to 0.01), as compared with the patients on placebo; this included
      both the average number of awakenings per week (p = 0.04), and the mean number of
      nights with awakenings per week (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351054
TI  - Dynamics of atrial natriuretic factor-guanylate cyclase receptors and receptor
      ligand complexes in cultured glomerular mesangial and renomedullary interstitial
      cells.
AB  - The dynamics of the guanylate cyclase receptor of atrial natriuretic factor (GCA
      ANF receptor) were investigated in cultured glomerular mesangial and
      renomedullary interstitial cells from the rat. In these cells, the GCA-ANF
      receptor did not mediate internalization and lysosomal hydrolysis of 125I-ANF1-28
      and did not undergo ligand-induced endocytosis. Glomerular mesangial cells were
      able, however, to mediate internalization and lysosomal hydrolysis of 125I-ANF1
      28 via clearance ANF (C-ANF) receptors and to promote rapid receptor-mediated
      internalization and lysosomal hydrolysis of 125I-(Sar1) angiotensin II.
      Radioligand specifically bound to surface GCA-ANF receptors was rapidly
      dissociated at 37 degrees C (k(off) greater than 0.8 min-1), with a Q10(30-37
      degrees C) greater than 6. The dissociation was markedly slower at
      subphysiological temperatures (Q10(4-30 degrees C), 2-3) or in the presence of
      0.5 mM amiloride. The results demonstrate that the GCA-ANF receptor, contrary to
      C-ANF receptors and most other polypeptide hormone receptors, is a membrane
      resident protein that does not mediate internalization and lysosomal hydrolysis
      of ligand. The termination of the interaction of ANF with GCA-ANF receptors
      results from a physiological process that leads to rapid dissociation of receptor
      ligand complexes. The unique dynamics of GCA-ANF receptor-ligand complexes are
      likely to contribute importantly to stimulus-response homeostasis of ANF.

PMID- 1351055
TI  - Intercellular adhesion molecule-1 gene expression in human endothelial cells.
      Differential regulation by tumor necrosis factor-alpha and phorbol myristate
      acetate.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is an inducible glycoprotein expressed
      on the surface of inflamed endothelium which mediates in part the extravasation
      of granulocytes into sites of infection or injury. ICAM-1 mRNA is not detected in
      unstimulated human umbilical vein endothelial cells (HUVECs), but accumulates
      transiently following tumor necrosis factor-alpha (TNF-alpha) or phorbol
      myristate acetate (PMA) treatment with maximal steady state levels occurring at 2
      or 4 h, respectively. Pretreating HUVECs with PMA for 72 h down-regulates protein
      kinase C and inhibits the subsequent induction of ICAM-1 mRNA by PMA, but does
      not affect TNF-alpha-induced message accumulation. Nuclear run-on assays showed
      that the ICAM-1 gene is transcribed under basal conditions in HUVECs, and that
      TNF-alpha stimulates transcriptional activity 3- to 4-fold within 30 min of
      treatment. In contrast, PMA has little effect on ICAM-1 gene transcription up to
      4 h following stimulation. Message stability studies established that ICAM-1 mRNA
      induced by PMA has a longer half-life than the TNF-alpha-induced message. These
      results suggest that PMA acts through protein kinase C to up-regulate ICAM-1
      expression primarily at a post-transcriptional level by stabilizing ICAM-1 mRNA,
      whereas TNF-alpha transcriptionally regulates ICAM-1 gene expression through an
      undefined, protein kinase C-independent pathway.

PMID- 1351056
TI  - Regulated coupling of the Neu receptor to phosphatidylinositol 3'-kinase and its
      release by oncogenic activation.
AB  - The neu protooncogene encodes a tyrosine kinase receptor that is involved in the
      regulation of normal growth and malignant transformation. To circumvent the use
      of the incompletely characterized ligand of Neu, we constructed a chimeric
      protein composed of the ligand-binding domain of the epidermal growth factor
      receptor and the transmembrane and cytoplasmic portions of Neu. By expressing
      this Neu-epidermal growth factor receptor chimera (termed NEC), we found that
      following stimulation by the heterologous ligand, the tyrosine kinase of Neu
      became associated with a phosphatidylinositol (PI) kinase activity. The
      association was dependent on the concentration of the ligand and was almost
      maximal within 30 s after ligand binding. The lipid kinase was identified as a
      type I PI 3'-kinase on the basis of its inhibition by Nonidet P-40 and high
      pressure liquid chromatography of the phosphorylated product. To confirm the
      identification of PI 3'-kinase as an effector of Neu, we raised antibodies to the
      alpha-isoform of the regulatory subunit of PI 3'-kinase (p85). Using these
      antibodies, it was possible to directly demonstrate ligand-dependent formation of
      a tyrosine-phosphorylated complex of NEC and PI 3'-kinase. Apparently, both PI 3'
      kinase and phospholipase C gamma, another substrate of the Neu kinase,
      simultaneously associated with the same activated NEC molecule. Nevertheless,
      immunofluorescence localization of PI 3'-kinase revealed no significant cellular
      redistribution of the enzyme after activation of the Neu kinase. Interestingly,
      PI 3'-kinase was localized primarily to the cell nucleus and to confined regions
      of the plasma membrane. Analysis of mutants of the Neu protein indicated that the
      oncogenic point-mutated Neu (Glu664) was permanently coupled to PI 3'-kinase; but
      two nontransforming versions of the oncoprotein, a kinase-defective protein and a
      carboxyl-terminally deleted Neu, were devoid of the constitutive association with
      PI 3'-kinase. Hence, we concluded that phosphatidylinositol 3'-kinase is a
      physiological substrate of the Neu receptor, but the regulation of this coupling
      is released upon oncogenic activation.

PMID- 1351057
TI  - Overexpression of the alpha-thyroid hormone receptor in avian cell lines. Effects
      on expression of the malic enzyme gene are selective and cell-specific.
AB  - The role of the alpha-thyroid hormone receptor (TR alpha) in regulation of
      transcription of the gene for chicken malic enzyme was analyzed in fibroblast
      cell lines normally unresponsive to triiodothyronine (T3). The gene for this
      transcription factor was introduced stably and overexpressed using a replication
      competent retroviral vector. In chick embryo fibroblasts (CEF), overexpression of
      TR alpha decreased malic enzyme activity by 90% in the absence of T3. Addition of
      T3 almost completely restored malic enzyme activity to the level of similarly
      treated control CEF infected with virus lacking TR alpha. These TR alpha-induced
      changes in malic enzyme activity were mediated by alterations in transcription of
      the malic enzyme gene. Similar results were obtained when transcriptional
      activity of TR alpha was analyzed using a transient co-transfection system. Thus,
      the unliganded TR alpha is a transcriptional repressor of the malic enzyme gene;
      binding of T3 to the receptor abolishes this repression. In contrast, stable
      overexpression of TR alpha in QT6 cells had no effect on malic enzyme expression
      in the absence or presence of T3. Nuclear T3 binding was equally high in CEF and
      QT6 cells overexpressing TR alpha. These findings suggest that cell-specific
      factors control the ability of TR alpha to regulate the malic enzyme gene.
      Overexpression of TR alpha in CEF had no effect on the expression of fatty acid
      synthase and acetyl-CoA carboxylase, lipogenic enzymes that are stimulated by T3
      in hepatocytes in culture. Thus, gene-specific factors also may control the
      transcriptional activity of TR alpha.

PMID- 1351059
TI  - Eighth International Symposium on Preparative Chromatography. Arlington,
      Virginia, May 13-15, 1991.

PMID- 1351058
TI  - The glycophosphatidylinositol-anchored Thy-1 molecule interacts with the p60fyn
      protein tyrosine kinase in T cells.
AB  - Stimulation of murine T cells by engagement of the multi-component T cell antigen
      receptor or by cross-linking the Thy-1 molecule leads to a similar response
      characterized by lymphocyte activation and lymphokine production. The early
      biochemical events induced by engaging these molecules also are similar and begin
      with activation of a tyrosine kinase pathway and tyrosine phosphorylation of a
      comparable set of substrates. Previous work demonstrates that the protein
      tyrosine kinase p60fyn is associated with the antigen receptor and therefore it
      may participate in the tyrosine phosphorylations that are observed with antigen
      receptor signaling. In this study we demonstrate that the Thy-1 molecule is also
      associated with p60fyn in a murine T cell hybridoma and in murine thymocytes. The
      interaction is independent of antigen receptor expression. Thy-1 is a member of
      the class of molecules anchored to the plasma membrane by a
      glycophosphatidylinositol (GPI) group. The association of Thy-1 with p60fyn is
      dependent on the GPI linkage, since cleavage of the GPI anchor disrupts the
      interaction. The association of Thy-1 and p60fyn suggests a means by which Thy-1
      cross-linking leads to tyrosine phosphorylation and T cell activation.

PMID- 1351060
TI  - Evidence for the involvement of beta-adrenergic receptors in conditioned
      immunomodulation.
AB  - This study investigates the role of beta-adrenergic receptors in the
      immunomodulatory effects of a conditioned aversive stimulus (CS). A CS is an
      environmental event that is not inherently aversive, but acquires aversive
      properties through pairings with a stimulus such as electric shock. This study
      evaluated the effects of administration of the beta 1-receptor selective
      antagonist atenolol, and the beta 2-receptor antagonist ICI 118,551 on
      conditioned immune alterations. Administration of either antagonist prior to
      presentation of the CS resulted in a dose-dependent attenuation of the CS-induced
      suppression of splenic T-cell proliferative response to concanavalin A,
      phytohemagglutinin, and the combination of ionomycin/phorbol-myristate-acetate.
      Furthermore, both antagonists dose-dependently attenuated the CS-induced
      suppression of gamma-interferon production by concanavalin-A (ConA)-stimulated
      splenocytes. In contrast, neither antagonist significantly attenuated the CS
      induced suppression of the B-cell mitogenic response to LPS, interleukin-2
      production, natural killer cell activity, or mitogenic responsiveness of blood
      lymphocytes. Thus it is likely that multiple mechanisms are involved in CS
      induced immune alterations and these results clearly implicate beta 1 and beta 2
      adrenergic receptors in a subset of immunomodulatory effects.

PMID- 1351061
TI  - Immunomodulatory effects of therapeutic gold compounds. Gold sodium thiomalate
      inhibits the activity of T cell protein kinase C.
AB  - Previous studies have shown that the gold compounds, gold sodium thiomalate (GST)
      and auranofin (AUR), which are effective in the treatment of rheumatoid
      arthritis, inhibit functional activities of a variety of cells, but the
      biochemical basis of their effect is unknown. In the current studies, human T
      cell proliferation and interleukin 2 production by Jurkat cells were inhibited by
      GST or AUR at pharmacologically relevant concentrations. Because it has been
      documented that protein kinase C (PKC) is involved in T cell activation, the
      capacity of gold compounds to inhibit PKC partially purified from Jurkat cells
      was assayed in vitro. GST was found to inhibit PKC in a dose-dependent manner,
      but AUR caused no significant inhibition of PKC at pharmacologically relevant
      concentrations. The inhibitory effect of GST on PKC was abolished by 2
      mercaptoethanol. To investigate the effect of GST on the regulation of PKC in
      vivo, the levels of PKC activity in Jurkat cells were examined. Cytosolic PKC
      activity decreased slowly in a concentration- and time-dependent manner as a
      result of incubation of Jurkat cells with GST. To ascertain whether GST inhibited
      PKC translocation and down-regulation, PKC activities associated with the
      membrane and cystosolic fractions were evaluated after phorbol myristate acetate
      (PMA) stimulation of GST incubated Jurkat cells. Translocation of PKC was
      markedly inhibited by pretreatment of Jurkat cells with GST for 3 d, but the
      capacity of PMA to down-regulate PKC activity in Jurkat cells was not altered by
      GST preincubation. The functional impact of GST-mediated downregulation of PKC in
      Jurkat cells was examined by analyzing PMA-stimulated phosphorylation of CD3.
      Although GST preincubated Jurkat cells exhibited an increased density of CD3, PMA
      stimulated phosphorylation of the gamma chain of CD3 was markedly inhibited.
      Specificity for the inhibitory effect of GST on PKC was suggested by the finding
      that GST did not alter the mitogen-induced increases in inositol trisphosphate
      levels in Jurkat cells. Finally, the mechanism of the GST-induced inhibition of
      PKC was examined in detail, using purified PKC subspecies from rat brain. GST
      inhibited type II PKC more effectively than type III PKC, and also inhibited the
      enzymatic activity of the isolated catalytic fragment of PKC. The inhibitory
      effect of GST on PKC activity could not be explained by competition with
      phospholipid or nonspecific interference with the substrate. These data suggest
      that the immunomodulatory effects of GST may result from its capacity to inhibit
      PKC activity.

PMID- 1351064
TI  - [XXXIVth Congress of the Federation of French-Speaking Gynaecologists and
      Obstetricians. Quebec City, 15-19 June 1992].

PMID- 1351063
TI  - An immunohistochemical study of the telencephalon of the senegal bichir
      (Polypterus senegalus).
AB  - The telencephalon in ray-finned fish (actinopterygians) is everted, in contrast
      to the evaginated telencephalic hemispheres in all other vertebrates. In the more
      derived ray-finned fish, the teleosts, proliferation of neurons and their
      migration from the ependymal zone of the pallium renders comparisons between
      telencephalic cell groups of the teleosts and members of other vertebrate groups
      extremely difficult. The telencephalon of Polypterus (a primitive living ray
      finned fish), although everted, is cytoarchitecturally much simpler than that of
      teleosts. We have thus applied immunohistochemical techniques to the study of the
      telencephalon of Polypterus to help clarify the evolution of the telencephalon in
      teleosts and facilitate comparisons between the telencephalon in ray-finned fish
      and other vertebrates. Antisera against the following neuroactive substances were
      used: 1) serotonin (5HT), 2) tyrosine hydroxylase (TH), 3) substance P (SP), 4)
      leucine-enkephalin (ENK), 5) neuropeptide Y (NPY), and 6) the neurotensin-related
      hexapeptide LANT6. Several features of the labeling patterns obtained suggested
      that the dorsal and ventral subdivisions of the area ventralis are homologous as
      a field to the basal ganglia and septum plus other basal telencephalic regions of
      land vertebrates, sharks and lungfish: 1) an abundance of SP+, NPY+, and ENK+
      fibers; 2) an abundance of TH+ fibers, possibly of posterior tubercle/tegmental
      origin; 3) the presence of an SP+ fiber bundle that appeared to descend from
      basal telencephalic levels and terminate in the posterior tubercle/tegmentum,
      which contain TH+ (possibly dopaminergic) neurons; and 4) an abundance of 5HT+
      fibers, presumably of posterior tubercle/tegmental origin. It was not possible,
      however, to recognize distinct pallidal and striatal subdivisions within the area
      ventralis of Polypterus. The olfactory pallium (P1) was generally poor in most of
      the substances examined, except for the presence of LANT6+ fibers. The P3 pallial
      field was conspicuously rich in SP+ and ENK+ fibers throughout its extent, and
      the caudal and lateral parts of the P2 field were rich in SP+ fibers and ENK+
      fibers. Since this is characteristic of the medial pallial and/or dorsomedial
      pallial walls of the telencephalon in lungfish, sharks, frogs, and reptiles, the
      P3 field and caudolateral part of the P2 field may be homologous to these
      portions of the telencephalon in other vertebrates. More rostromedial parts of P2
      may correspond to those parts of the pallium in land vertebrates that are in
      receipt of specific sensory input from the thalamus, since low neuropeptide
      levels are characteristic of these regions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1351065
TI  - [Evaluation of diagnostic technologies for congenital malformations].

PMID- 1351062
TI  - Major histocompatibility complex class III genes and susceptibility to
      immunoglobulin A deficiency and common variable immunodeficiency.
AB  - We have proposed that significant subsets of individuals with IgA deficiency (IgA
      D) and common variable immunodeficiency (CVID) may represent polar ends of a
      clinical spectrum reflecting a single underlying genetic defect. This proposal
      was supported by our finding that individuals with these immunodeficiencies have
      in common a high incidence of C4A gene deletions and C2 rare gene alleles. Here
      we present our analysis of the MHC haplotypes of 12 IgA-D and 19 CVID individuals
      from 21 families and of 79 of their immediate relatives. MHC haplotypes were
      defined by analyzing polymorphic markers for 11 genes or their products between
      the HLA-DQB1 and the HLA-A genes. Five of the families investigated contained
      more than one immunodeficient individual and all of these included both IgA-D and
      CVID members. Analysis of the data indicated that a small number of MHC
      haplotypes were shared by the majority of immunodeficient individuals. At least
      one of two of these haplotypes was present in 24 of the 31 (77%) immunodeficient
      individuals. No differences in the distribution of these haplotypes were observed
      between IgA-D and CVID individuals. Detailed analysis of these haplotypes
      suggests that a susceptibility gene or genes for both immunodeficiencies are
      located within the class III region of the MHC, possibly between the C4B and C2
      genes.

PMID- 1351066
TI  - [Echography and fetal weight: a re-evaluation].

PMID- 1351067
TI  - [The Doppler: evaluation and significance of anomalies].

PMID- 1351068
TI  - [Current and future indications for umbilical cord puncture].

PMID- 1351069
TI  - [The need for the services of fetal medicine and biology].

PMID- 1351070
TI  - [Molecular biology of the hormonal receptors in the genital tract].

PMID- 1351071
TI  - [Structure and expression of the genes encoding the enzymes for ovarian and
      peripheral steroidogenesis].

PMID- 1351072
TI  - [Role of inhibin and activin during the development and maturation of the
      reproductive system].

PMID- 1351073
TI  - [Prediction and prevention of pre-eclampsia. Importance of new epidemiological
      methods].

PMID- 1351074
TI  - [Biological prediction of pre-eclampsia: the vasoactive substances].

PMID- 1351075
TI  - [Biological tests in the prediction of pre-eclampsia].

PMID- 1351076
TI  - [Prediction and prevention of pre-eclampsia: the Doppler].

PMID- 1351079
TI  - [The progress accomplished and to be accomplished (1980-1992) in the pathogenesis
      and treatment of pre-eclampsia].

PMID- 1351080
TI  - [Medically assisted procreation: when to intervene and where to stop?
      Introduction and problems].

PMID- 1351078
TI  - [Prevention of intrauterine growth retardation and pre-eclampsia by small doses
      of aspirin. Results of the french multicenter trial EPREDA and comparison with
      data in the literature; value of uterine Doppler].

PMID- 1351077
TI  - [Prediction of pre-eclampsia: ambulatory arterial hypertension].

PMID- 1351081
TI  - [What is the role of medically assisted procreation in the treatment of female
      sterility (including unexplained sterility)?].

PMID- 1351082
TI  - [Medically assisted procreation: when to intervene and where to stop. Economic
      aspects].

PMID- 1351083
TI  - [Medically assisted procreation: legal analysis and precepts].

PMID- 1351084
TI  - [Ethical aspects of medically assisted procreation].

PMID- 1351085
TI  - T cell receptor-alpha beta lacking the beta-chain V domain can be expressed at
      the cell surface but prohibits T cell maturation.
AB  - A TCR-beta gene lacking V domain sequences (delta V-TCR-beta) was inserted into
      the germline of mice. Expression of the transgene inhibited endogenous TCR-beta,
      but not TCR-alpha gene rearrangement and expression. The mutated TCR-beta gene
      affected alpha beta T cell development: the common thymocyte pool was normal in
      cell number, with cells expressing CD4 and CD8, but the mature, "CD3bright"
      population expressing either CD4 or CD8 molecules was reduced by 90%. To help
      understand these effects on TCR-beta gene rearrangement and T cell development,
      biosynthesis of the delta V-TCR-beta protein was analyzed in a tumor cell line
      derived from a transgenic mouse. Despite absence of the V domain, the delta V-TCR
      beta chain paired with endogenous TCR-alpha chains and assembled with CD3 gamma, 
      delta, -epsilon, and -zeta components in the endoplasmatic reticulum, followed by
      transport through the Golgi complex to the plasma membrane. Therefore, assembly
      of the complex, and even cell surface expression, may be relevant for allelic
      exclusion of the TCR-beta gene. In the common thymocyte population, the CD3
      components, endogenous TCR-alpha, and the delta V-TCR-beta gene product were
      expressed at the RNA level, but endogenous TCR-beta was not. The TCR-alpha delta
      beta/CD3 complex was present at the cell surface at low levels and was functional
      in terms of anti-CD3-induced Ca2+ mobilization. The observed arrest of alpha beta
      T cell development at the CD4+8+ thymocyte stage indicates that ligand
      recognition by the TCR, with contribution of the beta-chain V domain, is not
      required for transition of CD4-8- thymocytes to the CD4+8+ phenotype, but
      necessary for entry into the "single positive," CD3bright differentiation stage.

PMID- 1351086
TI  - Generation of B cell memory and affinity maturation. Induction with Th1 and Th2 T
      cell clones.
AB  - We used an adoptive transfer system and CD4+ T cell clones with defined
      lymphokine profiles to examine the role of CD4+ T cells and the types of
      lymphokines involved in the development of B cell memory and affinity maturation.
      Keyhole limpet hemocyanin (KLH)-specific CD4+ Th2 clones (which produce IL-4 and
      IL-5 but not IL-2 or IFN-gamma) were capable of inducing B cell memory and
      affinity maturation, after transfer into nude mice or after transfer with
      unprimed B cells into irradiated recipients and immunization with TNP-KLH. In
      addition, KLH-specific Th1 clones, which produce IL-2 and IFN-gamma but not IL-4
      or IL-5, were also effective in inducing B cell memory and high affinity anti-TNP
      specific antibody. The induction of affinity maturation by Th1 clones occurred in
      the absence of IL-4, as anti-IL-4 mAb had no effect on the affinity of the
      response whereas anti-IFN-gamma mAb completely blocked the response. Th1 clones
      induced predominantly IgG2a and IgG3 antibody, although Th2 clones induced
      predominantly IgG1 and IgE antibody. We thus demonstrated that some Th1 as well
      as some Th2 clones can function in vivo to induce Ig synthesis. These results
      also suggest that a single type of T cell with a restricted lymphokine profile
      can induce both the terminal differentiation of B cells into antibody secreting
      cells as well as induce B cell memory and affinity maturation. Moreover, these
      results suggest that B cell memory and affinity maturation can occur either in
      the presence of Th2 clones secreting IL-4 but not IFN-gamma, or alternatively in
      the presence of Th1 clones secreting IFN-gamma but not IL-4.

PMID- 1351087
TI  - Alloantigenicity of human endothelial cells. 1. Frequency and phenotype of human
      T helper lymphocytes that can react to allogeneic endothelial cells.
AB  - To determine the relative ability of allogeneic endothelial cells to stimulate
      helper T lymphocytes (HTL), human PBMC or purified T cells were incubated in
      conventional lymphocyte microcultures or in limiting dilution microcultures with
      allogeneic human umbilical vein endothelia (HUVE), with cytokine-treated
      allogeneic HUVE, or with allogeneic peripheral blood monocytes. These cultures
      were tested for IL-2 production as an index of HTL stimulation. Dose-response
      studies in conventional lymphocyte cultures indicated that allogeneic monocytes
      were better than allogeneic HUVE at stimulating IL-2 production. Limiting
      dilution analyses revealed that untreated HUVE and TNF-treated HUVE stimulated
      small numbers of HTL (approximately 1 HTL/30,000 PBMC), whereas 5 to 10 times
      more HTL were stimulated by IFN-gamma-treated HUVE and 10 to 20 times more HTL
      were stimulated by allogeneic monocytes. Serologic deletion studies revealed that
      most of the high frequency HTL responding to IFN-gamma-treated HUVE were CD4+,
      whereas most of the low frequency HTL responding to nontreated HUVE or to TNF
      treated HUVE were CD8+. Interestingly, mAb to MHC class I and class II molecules,
      which significantly impaired HUVE-induced proliferation, caused little
      interference with HUVE-induced IL-2 production. Finally, polymerase chain
      reaction analysis demonstrated that untreated allogeneic HUVE cells could
      stimulate PBMC to produce mRNA for IFN-gamma, as well as for IL-2. These data
      demonstrate the following hierarchy of allogeneic stimulatory capacity for human
      HTL: monocytes greater than IFN-gamma-treated HUVE much greater than TNF-treated
      HUVE = nontreated HUVE. Further, these data suggest that non-activated allogeneic
      endothelial cells can initiate immune responses by inducing IL-2 and IFN-gamma.
      Because IFN-gamma can induce MHC class II expression by the endothelial cells,
      this could recruit large numbers of CD4+ T cells for IL-2 production.

PMID- 1351088
TI  - Production of transmembrane and secreted forms of tumor necrosis factor (TNF)
      alpha by HIV-1-specific CD4+ cytolytic T lymphocyte clones. Evidence for a TNF
      alpha-independent cytolytic mechanism.
AB  - Candidate AIDS vaccines consisting of recombinant forms of the HIV-1 envelope
      glycoprotein induce, in seronegative human volunteers, an env-specific T cell
      response that includes CD4+, MHC class II-restricted CTL capable of lysing HIV-1
      infected target cells. In this study, we have analyzed the production of the
      cytokines TNF-alpha and lymphotoxin (LT) by a set of env-specific CD4+ human CTL
      clones. TNF-alpha and LT are of interest because of their potential role in
      target cell destruction by CD4+ CTL. Our studies focused on the possibility that
      a cell surface form of TNF-alpha expressed by CTL after physiologic activation
      with target APC might participate in the cytolytic reactions mediated by these
      clones. We found that, upon interaction with target cells expressing env epitopes
      in the context of the appropriate MHC class II molecules, CD4+ CTL released TNF
      alpha with kinetics that were rapid, compared with other cytokines, and that were
      generally similar to the kinetics of target cell destruction. LT secretion was
      not detected during the time course of the cytolytic reactions. A novel flow
      cytometric assay was used to show that physiologic activation of CD4+ CTL with
      target APC induced expression by the CTL of cell surface forms of TNF-alpha.
      Immunoprecipitations from activated, surface-iodinated CTL clones revealed two
      forms of surface TNF-alpha, a 26-kDa form, representing the transmembrane
      precursor of secreted TNF-alpha, as well as the 17-kDa secreted form bound to the
      cell surface. For a subset of CD4+ CTL, we found that treatment of CTL with
      cyclosporin A inhibited Ag-induced production of both transmembrane and secreted
      forms of TNF-alpha but had no effect on cytolysis. Thus, although transmembrane
      and secreted TNF-alpha produced by HIV-1-specific CD4+ CTL may have important
      effects in vivo, the rapid destruction of target APC by the set of CD4+ CTL
      clones described here occurs through a TNF-alpha-independent mechanism.

PMID- 1351089
TI  - The lymphocyte-specific tyrosine protein kinase p56lck is endocytosed in Jurkat
      cells stimulated via CD2.
AB  - Incubation of the human T cells, Jurkat, with two sets of activating anti-CD2 mAb
      (T11(2) + T11(3), D66 + T11(1)) induced delocalization of p56lck and CD2
      receptors from the plasma membrane and increased the tyrosine kinase activity of
      p56lck. The anti-CD2 mAb combination (T11(2) + T11(3)) that produced the most
      rapid increase in p56lck kinase activity also induced the most rapid
      delocalization of the kinase. In stimulated cells, both p56lck and CD2 receptors
      are detected in cytoplasmic vesicles. The internalization of p56lck in endocytic
      vesicles was established by confocal microscopy. By double staining it was shown
      that only part of the p56lck colocalized with the internalized CD2 receptor
      suggesting distinct sorting processes. Internalization of p56lck appeared to be
      specific of CD2 stimulation as: 1) in Jurkat cells triggered with an anti-CD3
      mAb, p56lck was not internalized whereas CD3 receptors were completely
      endocytosed; 2) when cells were stimulated via CD4, the kinase and CD4 receptors
      remained associated with the plasma membrane. In addition, internalization of
      p56lck upon stimulation of CD2 receptors was not modified in CD2+/CD3-Jurkat
      cells indicating that CD3 is not involved in this process. The identification of
      different subcellular localizations of p56lck in resting and stimulated T cells
      should represent an important step in the definition of its functional activity.

PMID- 1351090
TI  - Reduced susceptibility to HIV-1 infection of ethyl-methanesulfonate-treated CEM
      subclones correlates with a blockade in their protein kinase C signaling pathway.
AB  - We have described the isolation of chemically induced CEM subclones that express
      CD4 receptors and bind soluble gp120, yet show a markedly reduced susceptibility
      to infection with HIV-1. Two subclones were found to have an abnormal response to
      the protein kinase C (PKC) activator PMA. PMA treatment induced CD3 and CD25 (IL
      2R) receptors on the parental line and on other ethyl-methanesulfonate-derived
      subclones, but not on these two mutants. Direct assays of PKC activity were
      conducted. Total cellular PKC enzymatic activity was found to be normal in these
      subclones. PMA-induced CD4 down-modulation occurred normally. In addition,
      activation of c-raf kinase was normal. Since HIV-1 long terminal repeat contains
      two functional nuclear factor kB (NF-kB) regulatory elements, we studied the
      ability of PMA to induce NF-kB binding activity by different assays.
      Chloramphenicol acetyl transferase (CAT) assays using the HIV-1 (-139)long
      terminal repeat-CAT construct showed no PMA induction of CAT activity in these
      subclones (unlike the parental line and other subclones). Okadaic acid, an
      inhibitor of phosphatases 1 and 2A, did not overcome the defect in these
      subclones. Gel retardation assays, using a 32P-probe containing the HIV-1 NF-kB
      probe and nuclear extracts from PMA-treated cells, showed significantly reduced
      induction of nuclear NF-kB binding proteins in these two subclones compared with
      wild type CEM and a control subclone. Deoxycholate treatment of cytoplasmic
      extracts from these subclones released much reduced NF-kB binding proteins from
      their cytoplasmic pools. Thus, reduced levels of PKC-induced nuclear NF-kB
      activity in two T cell subclones did not affect their normal cell growth, but
      correlated with a pronounced reduction in their susceptibility to HIV-1
      infection.

PMID- 1351091
TI  - Inhibition of S-phase progression in macrophages is linked to G1/S-phase
      suppression of DNA synthesis genes.
AB  - Some of the important controlling events regulating eukaryotic S-phase
      progression are considered to occur late in the G1 stage of the cell cycle. We
      show here that stimulation of DNA synthesis in bone marrow-derived macrophages
      (BMM) by macrophage CSF-1 is preceded by G1 expression of three genes which
      encode proteins associated with the DNA synthesis machinery--the M1 and M2
      subunits of ribonucleotide reductase and proliferating cell nuclear Ag (PCNA).
      Increased expression for these genes correlated well with the mitogenic response
      and sustained expression required de novo RNA and protein synthesis and also the
      presence of CSF-1 for at least most of G1. Inhibitors of BMM proliferation (LPS,
      TNF-alpha, IFN-gamma, and cAMP elevating agents) suppressed CSF-1-induced
      expression of M1, M2, and PCNA mRNA measured at 22 h. This suppression occurred
      even when added up to 12 h after the CSF-1, a period coinciding with the G1/S
      phase boundary. The delayed kinetics of this effect parallels the ability of
      these agents to maximally inhibit CSF-1-induced BMM DNA synthesis when added at
      similar times. Decreased expression of M1, M2, and PCNA was not merely a
      consequence of DNA synthesis inhibition because the S-phase inhibitor,
      hydroxyurea, did not suppress CSF-1-induced gene expression. These results
      suggest that inhibition of DNA synthesis by antiproliferative agents involves
      inhibition of expression of several genes associated with the DNA synthesis
      machinery.

PMID- 1351092
TI  - CD45 alternative exon expression in murine and human CD4+ T cell subsets.
AB  - Leukocytes express a family of high m.w. glycoproteins called leukocyte common Ag
      (CD45), which are involved in phosphotyrosine signal transduction. Antibodies to
      different CD45 isoforms distinguish functionally different CD4+ T cell subsets in
      humans, rats, and mice. Selected protein isoforms are expressed through a process
      of exon splicing that is cell-type and differentiation-state specific. Splicing
      of the three variable exons, A, B, and C, which encode amino acids located near
      the extracellular amino terminus of the protein, potentially results in
      generation of eight different mRNA transcripts. The purpose of the present study
      was to determine the relative levels of all eight different CD45 transcripts
      present in a panel of murine CD4+ T cell lines and normal murine and human CD4+ T
      cell subsets separated with antibodies to CD45 variable exons. We show, as
      expected, that the broad features of CD45 surface isoform expression in these
      cells can be accounted for by the relative amounts of the eight differentially
      spliced transcripts. Unexpectedly, all the differences in CD45 isoform expression
      among the CD4+ T cell subpopulations that we measured could be accounted for by
      differences in the overall level of variable exon expression. We did not see
      differences among T cell populations in the relative expression of particular
      variable exons. Exon B was always found in greater abundance than exons C or A.
      Of the dual exon species, only AB and BC were found in CD4+ T cells. The AC
      species was undetectable. Human CD4+ T cells, especially those in the naive
      subset, express higher levels of CD45 variable exons than murine CD4+ T cells.

PMID- 1351093
TI  - Multiple endocrine neoplasia syndrome--type 2b. Case report and review.
AB  - The multiple endocrine neoplasia syndromes are an association of tumours of 2 or
      more endocrine glands. Multiple endocrine neoplasia type 2b (MEN 2b) patients
      develop medullary thyroid carcinoma and pheochromocytomas as well as unique
      physical characteristics. Most commonly, MEN2b is inherited with an autosomal
      dominant pattern although sporadic cases are not uncommon. If untreated the
      disease may be lethal. The facial, oral and ocular characteristics are reliable
      markers of the disease. These patients give a history most commonly of slipped
      capital femoral epiphysis, hypertension and life-long diarrhoea and/or
      constipation. MEN2b is most commonly characterised by nodules on the anterior
      aspect of the tongue, thickened lips with nodules, thickened upper eyelids,
      broadened nasal bridge, thickened corneal nerves and dilated, symmetrical,
      pedunculated nodules on the cheek mucosa. The patient described has most of these
      characteristics. Radiographic features of the jaws which have not been previously
      described are reported. These include a markedly enlarged and bifurcated inferior
      alveolar canal and shortened roots of the lower incisor teeth. Due to the
      lethality of the disease, patients who present with the above physical
      characteristics must be further investigated to exclude MEN2b.

PMID- 1351094
TI  - Acute foot compartment syndromes.
AB  - Twelve cases of compartment syndrome of the foot in 10 patients were
      retrospectively reviewed. All were high-energy injuries sustained in a fall from
      a height (six), crush (three), or motor vehicle accident (three). Bone injuries
      of the foot included five calcaneal fractures, three multiple metatarsal and/or
      phalangeal fractures, and two Lisfranc fracture-dislocations with multiple
      metatarsal neck fractures. The most consistent physical finding was tense
      swelling of the foot. The diagnosis was confirmed with compartmental pressure
      measurements in all cases. Decompressive fasciotomies were adequately performed
      by the medial approach of Henry or a combined approach with medial and dorsal
      incisions. An additional lateral incision was used in two instances.

PMID- 1351095
TI  - Characterization of prejunctional alpha-2 adrenergic receptors involved in
      modulation of adrenergic transmitter release in the isolated perfused rat kidney.
AB  - The subclassification of alpha-2 adrenergic receptors into A and B subtypes is
      based on radioligand binding and functional studies. Radioligand binding studies
      also have suggested the existence of C and D subtypes, which have only been
      described as binding sites. This study was designed to determine the subtype of
      prejunctional alpha-2 adrenergic receptor involved in inhibition of
      norepinephrine release from sympathetic nerves in the rat kidney. Electrically
      induced (0.25 Hz, 50 V, 0.5 msec, 10 pulses) fractional tritium overflow was
      measured in kidneys isolated from male Sprague-Dawley rats and prelabeled with
      [3H]norepinephrine. The alpha-2 receptor antagonists rauwolscine and yohimbine
      did not enhance fractional tritium overflow, suggesting the lack of
      autoinhibition at this frequency of stimulation. The alpha-2 receptor agonist, UK
      14,304, inhibited electrically stimulated fractional tritium overflow with an
      ED50 of 4.85 +/- 0.35 nM. pA2 values for various alpha receptor antagonists
      against UK-14,304-induced inhibition of fractional tritium overflow were:
      rauwolscine, 8.8; yohimbine, 8.1; prazosin, 7.4; BAM 1303, 7.5; SKF 104078, 6.4;
      phentolamine, 8.7; WB 4101, 8.1; corynanthine, 6.1; and ARC-239, 7.2. The
      correlation coefficients and slopes of the regression lines between pA2 values of
      alpha receptor antagonists at the prejunctional alpha-2 adrenergic receptor and
      the reported pKi values obtained from radioligand binding studies were: 0.48 and
      0.82; 0.61 and 0.58; 0.53 and 0.85; and 0.89 and 1.05 for the alpha-2A, B, C and
      D adrenergic receptors, respectively. These data suggest that the prejunctional
      alpha-2 adrenergic receptor modulating [3H]norepinephrine release in the rat
      kidney most closely resembles the alpha-2D adrenergic receptor characterized by
      radioligand binding studies.

PMID- 1351096
TI  - Opposite rank order of potency for alpha-2 adrenoceptor agonists on water and
      solute excretion in the rat: two sites and/or receptors?
AB  - Preliminary studies determined that, unlike other purported alpha-2 adrenoceptor
      agonists, 2,6-dimethyl clonidine (2,6-DMC) increased urine flow rate independent
      of vasopressin. We therefore compared the dose-response curves of three alpha-2
      adrenoceptor agonists, clonidine, UK 14,304 and 2,6-DMC. Unilaterally
      nephrectomized Sprague-Dawley rats were anesthetized and the left kidney was
      exposed and the ureter cannulated. A 31-gauge needle was advanced into the renal
      artery to permit direct intrarenal infusion of the study drugs. All three
      agonists produced a dose-related increase in urine flow rate and sodium
      excretion. A clear opposite rank order of potency was observed when the urine
      flow rate was analyzed as free water and osmolar clearance. For free water
      clearance, clonidine much greater than UK 14,304 much greater than 2,6-DMC, with
      2,6-DMC producing little change. The effect on osmolar clearance was opposite
      with 2,6-DMC much greater than clonidine = UK 14,304. The V2 antagonist [1-(beta
      mercapto-beta,beta-pentamethylene-proprionic acid), 2-d-isoleucine,4
      isoleucine]arginine-vasopressin blocked the effects of clonidine but not 2,6-DMC.
      In a water-loaded rat model, 2,6-DMC but not clonidine increased the delivery of
      filtrate out of the proximal segments of the nephron. These results are
      consistent with the postulate that lower doses of 2,6-DMC increase solute
      excretion independent of vasopressin, possibly in proximal segments of the
      nephron. Clonidine on the other hand increases free water clearance and this
      effect is mediated through an interaction with the renal actions of vasopressin.
      Whether these disparate effects represent two distinct receptors or two sites of
      alpha-2 adrenoceptors in the kidney is not known.

PMID- 1351099
TI  - Epidural narcotics: mechanism of action and nursing implications.
AB  - Patients who receive narcotics by epidural injection or infusion have the
      potential to develop pharmacological side effects. Theories of epidural pain
      control and a brief review of spinal anatomy and pain physiology are presented in
      this article. Narcotic medications used for epidural infusion are
      pharmacologically distinguished by their hydrophilic or lipophilic character.
      Important side effects of epidurally administered narcotics, clinical
      presentation, manifestations, and appropriate nursing interventions are
      discussed.

PMID- 1351098
TI  - Possible location and function of neuropeptide Y receptor subtypes in the rat
      mesenteric arterial bed.
AB  - Earlier investigation of the vascular actions of Neuropeptide Y (NPY) led us to
      propose that distinct receptors mediated the prejunctional inhibition of
      periarterial nerve-stimulated norepinephrine (NE) release and the postjunctional
      potentiation of the increase in perfusion pressure elicited by vasoconstrictors.
      These receptors were designated Y2 and Y1, respectively, based on the ability of
      C-terminal fragments to mimic the former action. The present study investigates
      further the involvement of these putative receptor subtypes in the isolated and
      perfused mesenteric arterial bed. [Leu31Pro34]NPY, a novel analog with
      specificity at the Y1 receptors, potentiated the increase in perfusion pressure
      elicited by exogenously administered NE and arginine vasopressin, confirming the
      existence of this NPY subtype postjunctionally. This immediate and prolonged
      potentiation was abolished by phentolamine, attenuated by benextramine and the
      reputed NPY antagonist, PYX1. [11-36]NPY also produced a concentration-dependent
      potentiation of NE-stimulated increase in perfusion pressure suggesting that the
      Y2 receptor subtype may also be present postjunctionally in this model of the
      vascular neuroeffector junction. The finding that the profile of this
      potentiation differed from that elicited by [Leu31Pro34]NPY and, in contrast to
      the latter, was not attenuated by PYX1, intimates the existence of both distinct
      subtypes postjunctionally. [Leu31Pro34]NPY also reduced periarterial nerve
      stimulated release of NE with a concomitant reduction in perfusion pressure
      indicating, in addition to the Y2 subtype, the presence of the Y1 receptor
      prejunctionally in the rat mesenteric arterial bed.

PMID- 1351100
TI  - Biological versus psychosocial.

PMID- 1351101
TI  - The XIV World Congress of the International Society for Heart Research. Kobe,
      Japan, 10-14 May 1992. Abstracts.

PMID- 1351097
TI  - Postnatal development of organic cation transport and mdr gene expression in
      mouse kidney.
AB  - The apical surface of the proximal tubular epithelium is the site of both P
      glycoprotein localization and postulated active secretion of organic cations in
      the mammalian kidney. P-glycoprotein has been shown to act as a pleiotropic drug
      efflux pump across the cell membrane of tumor cells expressing the multidrug
      resistance phenotype, whereas the renal organic anion and organic cation
      secretory systems serve the function of pleiotropic drug transport across the
      proximal tubule epithelium. Because most known substrates for P-glycoprotein are
      organic cations, we tested the hypothesis that the physiological function of this
      protein in the kidney is to mediate renal organic cation secretion. In one
      approach, we compared the postnatal development of organic cation transport with
      that of kidney mdr gene expression. Cimetidine-sensitive uptake of classical
      substrates for renal secretion (N-methyl nicotinamide and tetraethylammonium)
      into kidney slices developed gradually in neonate mice, reaching adult capacity
      in 4 to 6 weeks. P-glycoprotein and its mRNA, as estimated by immunohistochemical
      methods and RNAse protection analysis, were undetectable at birth and were
      expressed abruptly at the adult level between 2 and 3 weeks of age. In another
      approach, classical inhibitors of renal organic cation secretion (cimetidine and
      cyanine 863) failed to reverse resistance to adriamycin in Chinese hamster ovary
      and P388 cell lines, which possess the phenotypic traits of multidrug resistance.
      These results suggest that the cimetidine-sensitive component of organic cation
      secretion is mediated by a protein other than the P-glycoprotein in the mammalian
      kidney.

PMID- 1351102
TI  - Satellite Symposia of the XIV World Congress of the International Society for
      Heart Research. Japan, May 1992. Abstracts.

PMID- 1351103
TI  - Effects of petrochemicals and ultraviolet radiation on epidermal IA expression in
      vitro.
AB  - We previously demonstrated that combined treatment of mice with crude oil and
      longwave ultraviolet radiation (UVA) led to the depletion of IA-positive cells
      from the epidermis. In the present study, we have developed an in vitro screening
      assay for combined effects of purified petrochemicals and UVA on epidermal IA and
      Thy-1 expression. This method involves removal of skin from donor mice prior to
      treatment with chemicals and UVA (20,000 J/m2), followed by in vitro culture and
      subsequent immunoperoxidase staining. In this study, a complete correlation was
      observed in terms of IA-positive cell density among similarly treated cultured
      skin and live mice. In vivo and in vitro studies both indicated that anthracene
      but not phenanthrene or benzo[a]pyrene led to significant depletion of both
      epidermal Langerhans cells and Thy-1-positive dendritic cells when followed by
      UVA treatment. The in vitro assay developed for this study should prove to be a
      valuable tool for the screening of a wide variety of chemicals for contact
      photosensitizing activity.

PMID- 1351104
TI  - Transcellular activation of the human immunodeficiency virus type 1 long terminal
      repeat in T lymphocytes requires CD4-gp120 binding.
AB  - Cells expressing human immunodeficiency virus type 1 (HIV-1) tat can
      transactivate the HIV-1 long terminal repeat (LTR) in cocultured T lymphocytes.
      In this report, we describe the molecular requirements for transcellular
      activation of the LTR in Jurkat cells. An analysis with deletion mutants and
      blocking antibodies demonstrated a requirement for env expression in addition to
      tat expression for transcellular activation to occur. The results suggest that
      the transient association of CD4 and gp120 in cocultured cells is required for
      tat-mediated transcellular activation. The events that follow CD4-gp120 binding
      in transactivation, however, do not require the gp120-neutralizing domain, in
      contrast to HIV-mediated fusion and infection. The consequences of this
      interaction on cellular function are currently under investigation.

PMID- 1351106
TI  - Symposium on Compensatory Mechanisms and their Limitations in Heart Failure. 55th
      annual scientific session of the Japanese Circulation Society. Kyoto, March 31,
      1991.

PMID- 1351107
TI  - [The 76th Congress of the Medico-Legal Society of Japan. Kanazawa, April 21-24,
      1992. Abstracts].

PMID- 1351105
TI  - Role of human T-cell leukemia virus type 1 X region proteins in immortalization
      of primary human lymphocytes in culture.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) immortalizes human CD4+ T lymphocytes
      in culture. Previous studies show that in the context of a herpesvirus saimiri
      vector, the sequence of the X region at the 3' end of the HTLV-1 genome is also
      capable of immortalizing CD4+ lymphocytes in the absence of HTLV-1 structural
      proteins. The X region of HTLV-1 encodes two trans-acting viral proteins, the 42
      kDa Tax protein and the 27-kDa Rex protein. Infection of human cord blood cells
      with herpesvirus saimiri recombinants which contain HTLV-1 X region sequences
      defective for expression of tax, rex, or both tax and rex demonstrates that tax
      function is necessary and sufficient for immortalization of primary human CD4+
      cord blood lymphocytes in culture in the context of the herpesvirus saimiri
      vector.

PMID- 1351108
TI  - [Immunohistochemical detection of carcinoembryonic antigen and P-glycoprotein in
      small cell lung cancer at diagnosis and relapse, with special reference to the
      tissue expression of CEA and response to chemotherapy].
AB  - Small cell lung cancer (SCLC) is one of the most sensitive tumors to drug
      therapy; however, the majority of patients eventually relapse within a few years.
      Emergence of drug resistance is thought to play a major role in the dismal course
      of this disease. However, the mechanism of drug resistance in SCLC still remains
      obscure. Based on the clinical observation that a significant proportion of
      patients with relapsing tumor show an elevated serum carcinoembryonic antigen
      (CEA) concentration while serum neuron-specific enolase (NSE) concentration
      remains normal, we attempted to determine whether the tissue of CEA is indicative
      of a clonal change in SCLC, in contrast with the tissue expression of NSE and P
      glycoprotein (P-gp). We examined 22 SCLC patients with tumor specimens available
      both at diagnosis and at relapse. Of the 22 patients, two had CEA expression at
      diagnosis, and a further three patients showed CEA expression at relapse. It is
      of note that there were two patients whose tumors expressed NSE alone at
      diagnosis but expressed CEA alone at relapse. Serum CEA concentration was
      concordant with the tissue expression of CEA; however, serum NSE concentration
      was not concordant with the tissue expression of NSE. Tumors with CEA expression
      at relapse were generally resistant to salvage chemotherapy, while there was no
      close relationship between the tissue expression of P-gp and refractoriness to
      drugs at relapse. These findings indicate that the tissue expression of CEA in
      SCLC is a marker of a clonal change during chemotherapy, and such a clonal change
      would play a role in the emergence of drug resistance in SCLC.

PMID- 1351109
TI  - [Airway epithelial beta 3-adrenergic receptor--effect on bioelectric properties
      and its mechanism of action].
AB  - To characterize the "atypical" beta-adrenergic receptor (beta 3-adrenergic
      receptor) and its action on ion transport across airway mucosa, we measured the
      bioelectric properties of canine cultured tracheal epithelium under short
      circuited conditions in vitro. Submucosal but mucosal addition of BRL37344, a
      selective beta 3-adrenergic agonist, increased short-circuit current (Isc) in a
      dose-dependent fashion, the EC50 value being 30 fold higher than that of
      isoproterenol. This effect on Isc was accompanied by the accumulation of
      intracellular cyclic AMP, and it was abolished by diphenylamine-2-carboxylate,
      bumetanide, and Cl-free medium, but not by amiloride. Pretreatment of cell with
      beta 1- and beta 2-adrenergic antagonists greatly reduced the Isc response to
      isoproterenol, whereas it had little effect on the BRL37344-induced response. In
      addition, the increase in Isc produced by BRL37344 was competitively antagonized
      by cyanopindolol, but pA2 was significantly different from the case of
      isoproterenol. These results suggest that beta 3-adrenergic receptors exist on
      airway epithelium, and may stimulate Cl secretion across the airway mucosa via
      accumulation of intracellular cyclic AMP.

PMID- 1351110
TI  - [A case of mediastinal teratoma--differentiation from lung abscess and
      bronchogenic carcinoma].
AB  - A 38-year-old man was admitted with persistent productive cough and right
      anterior chest pain. Chest X-ray showed two large masses connected with each
      other, one in the right lung field and the other in the anterior mediastinum. A
      tentative diagnosis of either lung abscess or bronchogenic carcinoma was
      initially made, because of elevated serum tumor markers (SLX and SCC) and
      persisting refractory inflammatory sings. However, open chest drainage revealed a
      few fine hairs and atheromatous materials within the masses, and the diagnosis of
      teratoma was made. We removed these masses, and investigated the reason for the
      elevation of tumor markers. Staining with SLX monoclonal antibody demonstrated
      that the pancreatic tissue in the masses contained SLX. Although this is the
      first reported case of teratoma producing tumor marker (SLX), it is highly
      possible that tumor markers may be elevated in the majority of patients with
      teratoma because of the genesis of this tumor.

PMID- 1351112
TI  - Homeobox genes and congenital malformations.
AB  - In this review we have built a case for abnormal Hox gene expression in human
      congenital malformations without presenting any direct evidence of their
      involvement. This approach is justified by the dramatic advances in developmental
      genetics which emphasize the considerable similarity in the primary processes and
      molecules used to guide early morphogenesis in all species. Hox genes occupy a
      central role in this scheme, being activated in a specific rostral-caudal order
      after initial specification of the basic embryonic axes and, thereafter,
      specifying positional identity by influencing downstream "realizator" genes that
      carry out the position-specific program. These theoretical arguments, together
      with the dramatic results obtained in an evolutionarily similar organism (the
      mouse) using the transgenic and gene deletion approaches, make it highly likely
      that abnormalities in Hox gene structure and expression will soon be implicated
      in specific human congenital malformation syndromes. In parallel with this
      phenotypic analysis, we can expect that the animal models discussed in this
      review will provide greater detail regarding the upstream regulators and
      downstream targets of Hox gene products. Together these approaches promise to
      finally elucidate some of the underlying mechanisms responsible for human
      congenital malformations.

PMID- 1351111
TI  - Activation of B virus (Herpesvirus simiae) in chronically immunosuppressed
      cynomolgus monkeys.
AB  - Three of 14 cynomolgus monkeys given the highest dose of an immunosuppressive
      drug in a 6-month toxicology study developed B virus (Herpesvirus simiae) oral
      lesions after 3 months of dosing. This necessitated early removal of all high
      dose monkeys from the study due to concerns related to B virus. The incidence and
      severity of parasitic (Oesphagostomum sp.) lesions of the large intestine were
      also increased in high-dose animals. Both B virus and Oesophagostomum are
      enzootic in macaques, and the lesions caused by them were considered secondary to
      chronic immunosuppression caused by the highest dose of the test compound.
      Evidence of immunosuppression included decreased lymphocyte counts (B-cells; CD2
      and CD8 T-cells), histopathologic evidence of lymphoid suppression, and serum
      induced inhibition of lymphocyte mitogen responses. Pathogenesis of the B virus
      was apparently associated with both activation of latent virus as well as
      transmission of active virus. Approaches for virologic monitoring of primates and
      for ensuring optimal safety for primate handlers are discussed.

PMID- 1351113
TI  - Role of CD4+ (helper) T cells in the pathogenesis of murine cytomegalovirus
      myocarditis.
AB  - Murine cytomegalovirus causes diffuse myocardial lesions in immunologically
      intact young adult male BALB/cBy mice. The cardiac changes develop in and around
      the small penetrating blood vessels of the heart where perivascular and
      interstitial infiltrates of macrophages and lymphocytes accumulate. Focal lesions
      of the coronary vessels and the endocardium also appear. When infected mice are
      depleted of CD4+ T lymphocytes, myocardial lesions fail to develop even though
      virus replication in the heart is enhanced. Contrary wise, when CD4+ cells are
      adoptively transferred into infected, thymectomized, irradiated, bone marrow
      repleted mice, focal perivascular necrotizing lesions of the heart develop.
      Depletion of CD8+ T lymphocytes fails to influence virus replication and the
      development of cardiac lesions. Endothelial and endocardial cells appear to be
      major sites of virus replication in the heart. Delayed hypersensitivity is
      hypothesized to be the mechanism of cardiac injury in this model system.

PMID- 1351114
TI  - High amount of epsilon-(gamma-glutamyl)lysine cross-links in Mallory bodies.
AB  - Alcoholic hepatitis, the most severe form of alcoholic liver disease, is
      associated with inflammation, liver cell necrosis, and the appearance of Mallory
      bodies (MBs) in hepatocytes. Identical MBs can be experimentally induced in mouse
      livers by chronic griseofulvin or 3,5-diethoxycarbonyl-1,4-dihydrocollidine
      treatment. MBs are filamentous cytoplasmic inclusions containing insoluble high
      molecular weight protein material. Covalent polymerization of intracellular
      proteins may occur through formation of epsilon-(gamma-glutamyl)lysine cross
      links catalyzed by Ca(2+)-dependent transglutaminases. Therefore, isolated
      experimentally-induced MBs were analyzed for the presence of epsilon-(gamma
      glutamyl)lysine bonds. Highly purified MBs contained 19.7 nmole (griseofulvin
      induced) and 14.4 nmoles (3,5-diethoxycarbonyl-1,4-dihydrocollidine induced) of
      isodipeptide linkage, respectively, per mg of protein. These results suggest that
      transglutaminase-induced cross-linking of proteins plays a major role in MB
      formation.

PMID- 1351115
TI  - Functional imaging of epileptic foci with PET and SPECT.
AB  - Functional imaging with PET and SPECT provides valuable information, helping
      lateralize and localize the site of an epileptogenic focus. SPECT imaging has
      been somewhat hampered by lower resolution than PET, and the lack of true
      "metabolic" radiopharmaceuticals, however SPECT perfusion studies may also help
      localize the seizure focus. At present, PET metabolic imaging with FDG is the
      most sensitive functional imaging modality for identifying epileptogenic foci.
      However with the current availability, lower cost and improved visualization, the
      diagnostic and prognostic efficacy of SPECT should increase.

PMID- 1351116
TI  - Antigen Presentation Functions of the MHC. Keystone Symposia on Molecular and
      Cellular Biology. March 5-11, 1992. Abstracts.

PMID- 1351117
TI  - Metal Ion/Molecular Biology Interface. Keystone Symposia on Molecular and
      Cellular Biology. March 13-19, 1992. Abstracts.

PMID- 1351118
TI  - Glycobiology. Keystone Symposia on Molecular and Cellular Biology. March 21-27,
      1992. Abstracts.

PMID- 1351119
TI  - Breast and Prostate Cancer. Keystone Symposia on Molecular and Cellular Biology.
      March 7-13, 1992. Abstracts.

PMID- 1351120
TI  - Spontaneous responsiveness to cytokines by human T-cell leukemias.
AB  - The molecular basis for autonomous growth of malignant forms of human T
      lymphocytes is not known. It can be investigated by functional responses of
      malignant cells in comparison with untransformed counterparts. At least two
      pathways (the CD2 and CD3 pathways) of human T-cell activation have been recently
      defined on the basis of monoclonal antibody activities in vitro, an experimental
      model exists which can be used to investigate which pathway of T-cell triggering
      might be involved in malignant growth. In untransformed T lymphocytes, responses
      to addition of cytokines are strictly controlled by signals which are mediated
      through triggering molecules including CD2 and CD3 and we therefore investigated
      20 freshly recovered human T leukemias with regard to spontaneous growth in
      response to interleukins. The majority of cases (16 out of 20) investigated
      displayed spontaneous responsiveness to cytokines (interleukins 1, 4, and 6),
      which might be related to activation signals mediated through the CD2 pathway.
      The functional repertoire of T leukemias did not correlate with expression of
      differentiation antigens conventionally employed for leukemia typing.

PMID- 1351121
TI  - Adhesion molecule expression does not influence the leukemic behavior of murine T
      cell lymphomas.
AB  - Recirculation and homing properties of normal lymphocytes are controlled by
      interactions with high endothelial venules (HEVs), specialized vessels which
      mediate the extravasation into lymphoid tissues. The present study was aimed at
      elucidating whether lymphoma-derived leukemic cell spreading and peripheral lymph
      node invasion ability are mediated by the recognition mechanisms which
      physiologically regulate normal lymphocyte trafficking. For this purpose, we
      tested the HEV-binding ability and the expression of the lymphocyte homing
      receptor (LHR) for peripheral lymph nodes as well as Pgp-1/CD44, LFA-1 and ICAM-1
      adhesion molecules by the highly leukemic cell line NQ22 in comparison with a
      series of non-leukemic murine T-lymphoma cell lines. Our results indicate that
      the hematogenous spreading as well as peripheral node invasion of lymphoma
      derived leukemic cells may occur independently of LHR expression. In addition,
      our findings seem to rule out that gross quantitative modifications in LFA-1 or
      ICAM-1 antigen expression are associated with differential dissemination
      abilities of transformed lymphoid cells.

PMID- 1351122
TI  - Comparisons between brain dopaminergic neurons of juvenile and aged rats: sex
      related differences.
AB  - It is known that several aspects of dopaminergic neurotransmission deteriorate
      with advanced age. In the present report, we have studied the possible existence
      of sexual differences in these aging-induced changes. Thus, we measured several
      pre- and postsynaptic biochemical parameters, indicative of the activity of
      dopaminergic neurons, in striatum, limbic forebrain and hypothalamic-anterior
      pituitary area of aged (24-26 months) and young (2 months) rats of both sexes.
      Tyrosine hydroxylase (TH) activity, as well as the number of D2-dopaminergic
      receptors, decreased in the striatum of aged rats, especially in the males in
      which the decrease in the number of receptors was associated with an increase in
      their affinity. In addition, the ratio between dopamine (DA) and its
      intraneuronal metabolite, L-3,4-dihydroxyphenyl-acetic acid (DOPAC), which can be
      used as an index of neurotransmitter turnover, was increased in aged females in
      parallel with a decreased DA content. In the limbic forebrain, TH activity was
      also decreased during aging, but only in males, whereas the DOPAC/DA ratio was
      increased in females, although in parallel with an increased DOPAC production.
      Finally, in the hypothalamic-anterior pituitary area, aging only affected the
      females, in which increased plasma prolactin levels were observed. This effect
      might be the result of a low responsiveness of pituitary lactotrophs to DA
      released from hypothalamic neurons, in spite of high prolactin levels producing a
      constant, although ineffective, stimulation of the activity of these neurons, as
      reflected by the high DOPAC content and DOPAC/DA ratio observed in the medial
      basal hypothalamus. In summary, these data allow us to suggest that the activity
      of brain dopaminergic neurons is modified with aging and there are significant
      differences as a function of sex and brain area.

PMID- 1351123
TI  - D-glucose transport systems in rat jejunal brush border membrane: influence of
      ageing.
AB  - Jejunal brush border membranes were isolated from rats of different ages (very
      young, young, adult and old); the gamma-GT specific activity and the vesicle
      volumes were unaffected by ageing, whilst protein content was significantly
      reduced in brush border from old rats. Vesicles were used to investigate the
      kinetics of Na-glucose cotransport under voltage-clamped and zero-trans
      conditions over a wide range of D-glucose concentrations (0.005-70 mM). Results
      provide evidence that in all the ages tested D-glucose can cross the brush border
      membrane both by a passive diffusional component and by two Na-dependent
      saturable transport systems, namely one with high-affinity and low-capacity and
      the other with low-affinity and high-capacity. However, in some old rats only one
      saturable and a very small passive component occur. The two Na-dependent
      transport systems were analyzed to define the stoichiometry of coupling between
      Na and glucose fluxes. In all the ages tested the Na:glucose ratio is higher in
      the high-affinity system than in the low-affinity one. Accordingly the effect of
      a superimposed membrane potential is more evident for the high-affinity transport
      mechanism. In conclusion, D-glucose transport systems seem to be unaffected by
      ageing from very young to adult rats; only in old animals age-related alterations
      can be observed.

PMID- 1351124
TI  - Lifelong ethanol consumption enhances the age-related changes in rat sympathetic
      neurons.
AB  - The effects of aging and chronic ethanol administration on the histochemical and
      morphometric features of rat superior cervical ganglion were studied in a rat
      strain selected for voluntary alcohol consumption. Ethanol was administered to
      the experimental group ad libitum (10% v/v in drinking water) from 3 months to 28
      months of age, the average ethanol intake being 6.4-5.4 g/kg per day. The
      sympathetic neurons of the ethanol consuming rats showed several signs of
      enhanced degeneration, e.g. decreased neuronal packing density, increased amount
      of age-pigment and decreased intensity of catecholamine histofluorescence and
      tyrosine hydroxylase immunoreactivity. The results may indicate a selective
      vulnerability of peripheral sympathetic neurons rather than a universal
      accelerated aging due to chronic ethanol exposure.

PMID- 1351125
TI  - Will I get AIDS?

PMID- 1351126
TI  - Immunisation with canarypox virus expressing rabies glycoprotein.
AB  - Poxviruses have many useful features as vectors for genes that carry immunising
      antigens from other viruses, such as ease of production and induction of cellular
      and humoral immunity, but there is concern about the safety of vaccinia virus. We
      turned to an avian poxvirus (canarypox); this virus undergoes abortive
      replication in mammalian cells that enables presentation of early gene products
      to the immune system. Canarypox virus was used as a vector for the rabies
      glycoprotein G gene. The safety and efficacy of the recombinant (ALVAC-RG; vCP65)
      were tested in several animal species, then it was subjected to a phase 1
      clinical trial. Twenty-five volunteers were randomly assigned to subcutaneous
      injections of the recombinant (three groups [A, B, and C] received two doses each
      of 10(3.5), 10(4.5), and 10(5.5) tissue-culture infectious doses50, respectively)
      or of human diploid cell culture vaccine (HDC; 6.52 international potency units
      per dose). 28 days after the second dose, all nine ALVAC-RG group-C subjects and
      two of three group-B subjects had rabies neutralising antibody concentrations of
      at least 0.5 IU/ml, the level associated with protection in animals. Although the
      geometric mean titre of these antibodies at that time was lower in group C than
      in the ten HDC recipients (4.4 [range 0.9-12.5] vs 11.5 [4.7-25.3] IU/ml), a
      single booster dose at 6 months induced a recall response in volunteers primed
      with either vaccine. Side-effects associated with ALVAC-RG were mild and of short
      duration and occurred at similar frequency to those of HDC vaccine. This study
      has shown the potential of non-replicating poxviruses as vectors for vaccination
      in human beings. Trials of canarypox-virus recombinants at higher doses and by
      other routes of administration are needed.

PMID- 1351127
TI  - Double-blind crossover comparison of human and porcine insulins in patients
      reporting lack of hypoglycaemia awareness.
AB  - There has been much debate about reports that some insulin-treated diabetic
      patients lose awareness of hypoglycaemic symptoms on changing from porcine to
      human insulin. In a double-blind, crossover study, we sought differences between
      porcine and human insulin in the frequency and characteristics of hypoglycaemic
      episodes among patients who reported a reduction of awareness of hypoglycaemia
      after changing treatment. We studied 50 patients referred by their physicians
      because of complaints of lack of awareness of hypoglycaemia on human insulin.
      They had had diabetes for a mean of 20 (SD 12) years and 70% had good or
      acceptable glycaemic control. Each patient was treated in a double-blind manner
      for four 1-month periods, two with human and two with porcine insulin, in random
      order. Only 2 patients correctly identified the sequence of insulin treatments
      used; 8 or 9 would have been expected to do so by chance alone. The mean
      percentage of hypoglycaemic episodes associated with reduced or absent awareness
      was 64% (SD 30%) for human insulin and 69% (31%) for porcine insulin. We could
      find no statistically significant differences between the insulin species with
      respect to glycaemic control or the frequency, timing, severity, or awareness of
      hypoglycaemia. Reduced hypoglycaemia awareness is common with both human and
      porcine insulins.

PMID- 1351128
TI  - Serum beta 2-microglobulin and prediction of progression to AIDS in HIV
      infection.
AB  - Identification of laboratory tests that can help predict progression to acquired
      immunodeficiency syndrome (AIDS) in people infected with human immunodeficiency
      virus (HIV) is important for clinical management and counselling. We have
      assessed the usefulness of CD4 lymphocyte count, serum beta 2-microglobulin
      concentration, and the presence of p24 antigen as predictors of AIDS. We studied
      214 homosexual and bisexual men with well-defined dates of HIV seroconversion.
      For each participant, we defined the baseline date as the earliest date before
      the development of AIDS on which the three laboratory tests were done. beta 2
      microglobulin concentration at baseline was in all analyses an independent
      predictor of AIDS, even after stratification by baseline CD4 count, duration of
      HIV infection, or use of zidovudine before or at baseline. For example, among men
      with at least 0.5 x 10(9)/l CD4 cells who were negative for p24 antigen, the
      risks of AIDS at 12 months and 24 months were 1% and 5%, respectively, for those
      whose beta 2-microglobulin concentrations were below 4.0 mg/l, compared with 17%
      and 27%, respectively for those with beta 2-microglobulin concentrations above
      that cut-off point (p less than 0.001). Among men with an estimated duration of
      infection of 5 years or less, beta 2-microglobulin concentration was the
      strongest independent predictor of AIDS. Measurement of serum beta 2
      microglobulin adds important prognostic information to CD4 count in determining
      the risk of progression to AIDS in HIV-infected subjects, including those whose
      CD4 cell count has not yet fallen.

PMID- 1351129
TI  - Mild cervical dyskaryosis: safety of cytological surveillance.
AB  - How best to manage women who are found on cervical screening to have mild
      dyskaryosis remains controversial. Cytological surveillance misses some lesions
      picked up by colposcopy, but colposcopy is emotionally traumatic for women, the
      majority of whom will have a normal result. To determine what proportion of
      lesions are missed by cytological surveillance, and whether any abnormalities
      persist after colposcopy, we studied, by means of colposcopy and biopsy, the
      prevalence of cervical intraepithelial neoplasia (CIN) and subclinical human
      papillomavirus infection (HPVI) in two groups of patients who had had a first
      smear showing mild dyskaryosis at least 24 months earlier. One group was
      recruited from a centre practising cytological surveillance, with colposcopy for
      patients showing persistent or progressive cytological abnormality. The other
      group all had early colposcopy and treatment. Of 214 patients recruited into the
      cytological surveillance group, 70 (33%) had been referred for colposcopy within
      24 months. Colposcopy of the remaining 144 (after a mean interval of 27 months
      from presentation) revealed that 54 (38%) were disease free, 64 (44%) had
      HPVI/CIN1, 8 (6%) had CIN2, and 18 (12%) had CIN3. A smear at that time
      identified 12 of the 18 (67%) with CIN3 as needing close cytological follow-up (1
      patient) or prompt referral for colposcopy (11 patients). 137 women in the early
      colposcopy group attended for the study colposcopy (after a mean interval of 32
      months from presentation). 37% were found to have some abnormality persisting
      after an earlier colposcopy, but none had CIN3. Cytological surveillance of mild
      dyskaryosis resulted in a 12% risk of patients having a small CIN3 lesion after 2
      years, but this risk was reduced to 4% by the addition of a third repeat smear 12
      months after the second. With such a policy only about a third of women would
      require colposcopy, and the risk of missing serious underlying precancerous
      changes would be low.

PMID- 1351130
TI  - Serological response to "Rochalimaea henselae" antigen in suspected cat-scratch
      disease.
AB  - There are no generally accepted diagnostic tests for cat-scratch disease (CSD),
      the cause of which is unknown. During the development of an indirect fluorescence
      antibody (IFA) test for detection of antibodies to "Rochalimaea henselae", sera
      from patients with CSD were found to have high titres to R henselae antigens.
      Further tests with this assay showed that 36 (88%) of 41 patients with suspected
      CSD had serum titres of 64 or more to R henselae antigen, that there was a low
      prevalence (3%) of substantial titres to R henselae in healthy controls (n =
      107), and that the immune responses to R henselae antigens were specific. These
      data suggest that the R henselae IFA test, or other serological assays based on R
      henselae, may be useful for diagnosis of CSD.

PMID- 1351131
TI  - Taxol.

PMID- 1351132
TI  - Canarypox virus as a vaccine vector.

PMID- 1351133
TI  - Cerebrovascular complications of primary herpes varicella-zoster infection.

PMID- 1351134
TI  - Medicinal Euroadvertising for 1993.

PMID- 1351135
TI  - Clinical implications of metastatic process.

PMID- 1351136
TI  - Natural history of autonomic neuropathy in chronic liver disease.
AB  - To determine the natural history of autonomic neuropathy in chronic liver disease
      we used standard cardiovascular autonomic tests to evaluate prospectively 60
      patients (33 male, 27 female) with initially well-preserved hepatic function. On
      initial testing, 27 patients (45%; median [range] age 56 [32-67] years) had vagal
      neuropathy. Autonomic dysfunction was equally common in patients with alcohol
      related and nonalcoholic-related liver disease. The cumulative 4-year mortality
      rate in patients with vagal neuropathy was 30% compared with 6% in those with
      normal autonomic function. Multiple logistic regression analysis showed that
      presence of vagal neuropathy and severity of hepatic damage were independent
      predictors of mortality. Serial testing showed that whereas disease progression
      occurred in some patients, in others mild abnormalities in autonomic function
      were reversible. Vagal dysfunction is common in well-compensated chronic liver
      disease and its presence identifies a subgroup of patients with a substantially
      worse outlook.

PMID- 1351137
TI  - A looming crisis: health in the Central Asian Republics.

PMID- 1351138
TI  - When science and politics collide.

PMID- 1351139
TI  - Life-sustaining treatment for brain-damaged child.

PMID- 1351141
TI  - HIV-infected children.

PMID- 1351140
TI  - HIV infection from dentist to patients.

PMID- 1351142
TI  - Lower mortality in cancer patients treated with low-molecular-weight versus
      standard heparin.

PMID- 1351143
TI  - Treatment of small cell carcinoma of the lung.

PMID- 1351144
TI  - Management of cancer pain.

PMID- 1351145
TI  - Aggressive endometriosis in bone.

PMID- 1351146
TI  - Diabetes: what sort of prevention?

PMID- 1351147
TI  - Management of intrahepatic cholestasis in pregnancy.

PMID- 1351148
TI  - Percutaneous needle decompression of small bowel.

PMID- 1351149
TI  - Glucose and insulin infusions during labour.

PMID- 1351150
TI  - Non-sexual papillomavirus transmission routes.

PMID- 1351151
TI  - Non-echogenic nuchal oedema as a marker in trisomy 21 screening.

PMID- 1351152
TI  - Protection against immune haemolytic disease of newborn infants by maternal
      monocyte-reactive IgG alloantibodies.

PMID- 1351153
TI  - Alteplase for hepatic veno-occlusive disease after bone-marrow transplantation.

PMID- 1351154
TI  - Outpatient cervical cerclage.

PMID- 1351155
TI  - Cancer of breast among men in electrical occupations.

PMID- 1351156
TI  - Histological grade of breast cancer in younger women.

PMID- 1351157
TI  - Loss of taste and terbinafine.

PMID- 1351158
TI  - Recombinant human erythropoietin for autologous blood donation.

PMID- 1351160
TI  - UK deaths from smoking.

PMID- 1351161
TI  - UK deaths from smoking.

PMID- 1351159
TI  - Obstetric anaesthesia.

PMID- 1351162
TI  - Blood donation.

PMID- 1351163
TI  - Blood donation.

PMID- 1351164
TI  - Priorities for safe motherhood initiative.

PMID- 1351165
TI  - Surgical dinners and overseas women.

PMID- 1351166
TI  - Familial clustering of HCV.

PMID- 1351167
TI  - Treatment of CMV retinitis.

PMID- 1351168
TI  - Prevalence of serum IgG antibodies to hepatitis A virus in Italian haemophiliacs.

PMID- 1351169
TI  - First-dose hypotension, ACE inhibitors, and heart failure in the elderly.

PMID- 1351170
TI  - Enterococcal superinfection in paediatric oncology patients treated with
      imipenem.

PMID- 1351171
TI  - Simvastatin use in children.

PMID- 1351173
TI  - Bioavailability of aluminium.

PMID- 1351172
TI  - Aluminium exposure in children associated with industrial waste.

PMID- 1351174
TI  - Bioavailability of aluminium.

PMID- 1351175
TI  - Bioavailability of aluminium.

PMID- 1351176
TI  - Biliary sludge.

PMID- 1351177
TI  - Kaposi's sarcoma and faecal-oral exposure.

PMID- 1351178
TI  - Kaposi's sarcoma and faecal-oral exposure.

PMID- 1351179
TI  - Postnatal transmission of HIV-1 associated with breast abscess.

PMID- 1351180
TI  - Prisoners' uptake of confidential, named HIV testing.

PMID- 1351181
TI  - Melanoma predicted by clinically atypical moles.

PMID- 1351182
TI  - Spectrophotometric examination of CSF for xanthochromia.

PMID- 1351183
TI  - Effect of allergen avoidance on development of allergic disorders in infancy.
AB  - There is much evidence that the development of allergic disorders may be related
      to early exposure of allergens, including those in breastmilk. We have tried to
      find out whether avoidance of food and inhaled allergens in infancy protects
      against the development of allergic disorders in high-risk infants. In a
      prenatally randomised, controlled study 120 infants with family history of atopy
      and high (greater than 0.5 kU/l) cord-blood concentrations of total IgE were
      allocated randomly to prophylactic and control groups. In the prophylactic group
      (n = 58), lactating mothers avoided allergenic foods (milk, egg, fish, and nuts)
      and avoided feeding their infants these foods and soya, wheat, and orange up to
      the age of 12 months; the infants' bedrooms and living rooms were treated with an
      acaricidal powder and foam every 3 months, and concentrations of Dermatophagoides
      pteronyssinus antigen(Der p l) in dust samples were measured by enzyme-linked
      immunosorbent assay. In the control group (n = 62), the diet of mothers and
      infants was unrestricted; no acaricidal treatment was done and Der p l
      concentrations were measured at birth and at 9 months. A paediatric allergy
      specialist unaware of group assignment examined the infants for allergic
      disorders at 10-12 months. Odds ratios were calculated by logistic regression
      analysis for various factors with control for other confounding variables. At 12
      months, allergic disorders had developed in 25 (40%) control infants and in 8
      (13%) of the prophylactic group (odds ratio 6.34, 95% confidence intervals 2.0
      20.1). The prevalences at 12 months of asthma (4.13, 1.1-15.5) and eczema (3.6,
      1.0-12.5) were also significantly greater in the control group. Parental smoking
      was a significant risk factor for total allergy at 12 months whether only one
      parent smoked (3.97, 1.2-13.6) or both parents smoked (4.72, 1.2-18.2).

PMID- 1351184
TI  - Effects of topical nasal anaesthesia on shift of breathing route in adults.
AB  - The position of the soft palate is known to determine the breathing route, but
      the physiological mechanisms that bring about a shift from nasal to oral
      breathing are unclear. To test the hypothesis that activation of receptors in the
      nasal passage may be involved in reflex initiation of oral breathing after nasal
      obstruction, we investigated respiratory responses to nasal occlusion before and
      after topical lignocaine anaesthesia of the nasal passages. Eleven volunteers
      were fitted with custom-made partitioned face masks, which separated nasal and
      oral passages. Air flow through each passage was detected by changes in airway
      pressure and carbon dioxide concentration. Nine subjects were habitual nasal
      breathers both before and after topical anaesthesia with 4% lignocaine. Among
      these subjects, the time to initiate oral breathing in response to nasal
      occlusion was significantly shorter before anaesthesia than afterwards (mean 4.4
      [SD 2.5] vs 10.8 [7.4] s, p less than 0.01). Similarly, the time to resume nasal
      breathing after release of nasal occlusion was significantly shorter before
      topical anaesthesia than afterwards (6.9 [4.9] vs 12.1 [7.8] s, p less than
      0.01). Topical anaesthesia did not affect respiration rate, end-tidal carbon
      dioxide concentration, or arterial oxygen saturation. These findings suggest that
      in human beings sensory information from receptors in the nasal passage has an
      important role in controlling the shift of breathing route.

PMID- 1351185
TI  - Intraepithelial gamma delta T-cell-receptor lymphocytes and genetic
      susceptibility to coeliac disease.
AB  - Although the proportion of gamma delta T-cell-receptor (TCR)-bearing
      intraepithelial lymphocytes is increased in the jejunum of patients with active
      coeliac disease, an abnormality thought to be specific among those with gluten
      sensitive enteropathy, the factors influencing gamma delta TCR expression remain
      uncertain. We examined the relation between genetic factors associated with
      coeliac disease and intraepithelial gamma delta T lymphocyte distribution in both
      coeliac patients and their healthy first-degree relatives. 41% (45/109) of
      healthy relatives had an increased density of gamma delta T cells in their mucosa
      and 66% had an increased density of alpha beta T cells. By contrast with alpha
      beta T cells, the density of gamma delta cells was significantly associated with
      genetic markers for coeliac disease susceptibility (DR3, DQA, and DQB). We also
      found a dose effect of DQA and DQB genes on the number of intraepithelial gamma
      delta T cells. An increased density of gamma delta T cells in normal jejunal
      mucosa of a healthy individual with appropriate genetic determinants might be
      necessary for the development of the typical lesions of coeliac disease. Routine
      jejunal histological studies should include gamma delta T-cell counts, thus
      allowing early detection of coeliac disease latency.

PMID- 1351186
TI  - No risk of diabetes after insulin-shock treatment.
AB  - Prophylactic insulin treatment is effective in preventing diabetes in animal
      models of insulin-dependent diabetes mellitus (IDDM) but the safety of such
      preventive treatment in prediabetic human subjects remains unclear; insulin is a
      potential autoantigen that could accelerate beta-cell decompensation and onset of
      IDDM. We have investigated whether insulin treatment of non-diabetic subjects
      increases the risk of subsequent development of diabetes in a retrospective study
      of Danish patients who received insulin-shock treatment for psychiatric
      disorders. Mean age of the 481 patients at insulin-shock treatment was 32.6
      (range 12.9-69.6) years. The patients received 59 (6-200) injections of 78 (16
      261) IU bovine/porcine insulin. Hospital records provided an average of 22.0 (0.6
      51.2) years' observation. During the observation time, IDDM developed in only 1
      patient; 1.3 cases would be expected from Danish incidence data (p = 0.75).
      Similarly, there was no significant difference between the observed number of
      cases of non-insulin-dependent diabetes mellitus (NIDDM) and the number expected
      from Danish prevalence data (12 vs 10.2; p = 0.45). We collected blood samples
      from 27 of the patients. All but 2 (who had previously diagnosed NIDDM) had
      normal fasting blood glucose and plasma insulin concentrations, none had islet
      cell antibodies, and only 2 had detectable insulin antibodies. Thus, the risk of
      diabetes was not increased by the use of many insulin injections in these non
      diabetic subjects. We conclude that clinical trials on prevention of IDDM by
      prophylactic insulin treatment can be regarded as safe.

PMID- 1351188
TI  - Growth retardation and immunodeficiency in a patient with mutations in the DNA
      ligase I gene.
AB  - DNA ligases are required for the replication, repair, and recombination of DNA. A
      cell line derived from a young woman with growth retardation, sun sensitivity,
      and immunodeficiencies, who died aged 19 with lymphoma, showed two different
      miscoding mutations at the DNA ligase I locus on chromosome 19, one in each
      allele. One of the mutations was inherited from the mother and has also been
      detected in two healthy brothers. The patient had features similar to those of
      Bloom's syndrome (BS), but cell lines from BS patients do not have mutations in
      the DNA ligase I gene. This patient seems to represent a distinct genetic entity.

PMID- 1351189
TI  - Common aetiological agent for epidemic and sporadic non-A, non-B hepatitis.
AB  - Enterovirus-like particles have been reported in the acute phase of both epidemic
      and sporadic non-A, non-B (NANB) hepatitis. To examine whether these particles
      were the causative agent in the two types of disease, 29 patients with acute
      viral hepatitis in a north Indian epidemic outbreak and 9 with sporadic acute
      disease were investigated. 25 (86%) of 29 patients with epidemic hepatitis and 5
      (56%) of 9 with sporadic disease were diagnosed as having enterically-transmitted
      NANB hepatitis by exclusion. Virus-like particles (VLP) of 30-34 nm were detected
      in stool of 1 patient with epidemic and 1 with sporadic hepatitis. The VLPs
      crossreacted serologically and a specific IgM response was seen in acute epidemic
      and sporadic serum samples. After inoculation with infected stool rhesus monkeys
      had a mild rise in liver enzymes, and bile samples contained VLPs. These results
      suggest that the aetiological agent in epidemic and sporadic disease is the same.

PMID- 1351187
TI  - Thyroid and other organ-specific autoantibodies in healthy centenarians.
AB  - To investigate the prevalence of thyroid autoantibodies in very old subjects, we
      assayed sera from 34 healthy centenarians (7 men, 27 women; age range 100-108
      years) for these antibodies. There was a clear age-dependent increase in
      prevalence of thyroid autoantibodies in sera from 549 control subjects aged 7-85
      years, prevalence in 40 subjects aged 70-85 being significantly greater (p less
      than 0.001, chi 2) than that in 436 subjects aged less than 50. By contrast,
      prevalence of thyroid autoantibodies in centenarians was not significantly
      different from that in controls aged less than 50. Cytofluorimetric analysis of
      peripheral blood lymphocytes showed a striking age-dependent decrease in total
      and CD5+B cells (without changes in their ratio), which reached its nadir in
      centenarians. The age-dependent increase in prevalence of thyroid autoantibodies
      in the elderly is not seen after the ninth decade of life. What relation this
      characteristic has to derangement of circulating B cells is unknown.

PMID- 1351190
TI  - The nose and the respiratory system.

PMID- 1351192
TI  - Vibration therapy for pain.

PMID- 1351191
TI  - Insulin for prophylaxis of insulin-dependent diabetes.

PMID- 1351193
TI  - Detecting vitamin A deficiency early.

PMID- 1351194
TI  - Horse manure after Rio.

PMID- 1351195
TI  - Pandolfi's box: research in Europe.

PMID- 1351196
TI  - Economic benefits of teaching patients with chronic obstructive pulmonary disease
      about their illness. The PASTMA Group.
AB  - By instructing patients in how to deal with their disease financial demands on
      health services may be reduced. 100 consecutive patients (aged 48 to 89) admitted
      to a general medical ward in Denmark with chronic obstructive pulmonary disease
      (COPD) were allocated randomly to receive either "personalized hospital practice"
      (PHP), which includes training in aspects of their disease, or standard hospital
      practice. Changes in "consumption" of health services per patient from 1 year
      before until 1 year after the intervention admission were evaluated in 82 (PHP
      group 42, controls 40) patients who completed the intervention phase. Each group
      contained about the same percentage of asthmatics and smokers. The increase in
      consumption of health services after intervention was on average Kr15,298 per
      patient per year less in the PHP group than in the control group (p = 0.048,
      Wilcoxon test). Consumption of general practitioner services was significantly
      increased in the control group compared with the PHP group (mean [95% Cl] Kr1346
      [549 to 2143] vs -89 [-423 to 245] per patient per year; p = 0.001, Wilcoxon
      test). These differences could not be explained by changes in smoking habits. PHP
      reduces the consumption of health services by patients with COPD, probably by
      increasing patients' knowledge of disease and hence their ability to manage
      themselves.

PMID- 1351197
TI  - Effect of presentation of partogram information on obstetric decision-making.
AB  - The way in which medical information is presented may affect doctors' decision
      making. We have assessed whether changing the appearance of the same information
      on the partogram affects clinical decisions during labour. Sixteen junior
      obstetricians were asked about how they would manage six hypothetical cases of
      difficult labour. Information was given by partogram, in which we varied either
      the relative scales of the x and y axes or whether the latent phase of labour had
      been included. Doctors were more likely to intervene and to intervene more
      actively if the progress of labour curve appeared flat and if the latent phase
      was included. The shape and point of origin of the partogram probably influence
      intervention rates in practice and may partly explain the low rates of caesarean
      section in some hospitals.

PMID- 1351198
TI  - Wine, alcohol, platelets, and the French paradox for coronary heart disease.
AB  - In most countries, high intake of saturated fat is positively related to high
      mortality from coronary heart disease (CHD). However, the situation in France is
      paradoxical in that there is high intake of saturated fat but low mortality from
      CHD. This paradox may be attributable in part to high wine consumption.
      Epidemiological studies indicate that consumption of alcohol at the level of
      intake in France (20-30 g per day) can reduce risk of CHD by at least 40%.
      Alcohol is believed to protect from CHD by preventing atherosclerosis through the
      action of high-density-lipoprotein cholesterol, but serum concentrations of this
      factor are no higher in France than in other countries. Re-examination of
      previous results suggests that, in the main, moderate alcohol intake does not
      prevent CHD through an effect on atherosclerosis, but rather through a
      haemostatic mechanism. Data from Caerphilly, Wales, show that platelet
      aggregation, which is related to CHD, is inhibited significantly by alcohol at
      levels of intake associated with reduced risk of CHD. Inhibition of platelet
      reactivity by wine (alcohol) may be one explanation for protection from CHD in
      France, since pilot studies have shown that platelet reactivity is lower in
      France than in Scotland.

PMID- 1351200
TI  - Reactive airways dysfunction after exposure to teargas.

PMID- 1351199
TI  - Meningitis, schools, and public alarm.

PMID- 1351201
TI  - IGE-mediated reaction to hydroxocobalamin injection in patient with pernicious
      anaemia.

PMID- 1351202
TI  - Extended (29 days) use of intravascular gas exchanger.

PMID- 1351203
TI  - Mycobacterial nucleic acids in sarcoid lesions.

PMID- 1351204
TI  - Helicobacter pylori seropositivity in symptom-free children.

PMID- 1351205
TI  - Mycobacterial nucleic acids in sarcoid lesions.

PMID- 1351206
TI  - Mis-sense mutation of alpha 1-antichymotrypsin gene associated with chronic lung
      disease.

PMID- 1351207
TI  - Diphtheria, pertussis, and tetanus vaccination.

PMID- 1351208
TI  - Cystic fibrosis carrier screening at first diagnosis of pregnancy in general
      practice.

PMID- 1351209
TI  - Population screening for cystic fibrosis.

PMID- 1351210
TI  - Severe dyserythropoiesis and autoimmune thrombocytopenia associated with
      ingestion of kelp supplements.

PMID- 1351211
TI  - Practicability of early treatment of acute stroke. Group for the Understanding of
      the Effects of the Stroke Syndrome; GUESS.

PMID- 1351212
TI  - Subclassification of strokes.

PMID- 1351213
TI  - Tests for renovascular disease.

PMID- 1351214
TI  - Quality of cardiopulmonary resuscitation.

PMID- 1351215
TI  - Quality of cardiopulmonary resuscitation.

PMID- 1351216
TI  - HCV genotypes in chronic hepatitis C and response to interferon.

PMID- 1351217
TI  - Is immunotherapy justified for recurrent spontaneous abortion?

PMID- 1351218
TI  - Abortion.

PMID- 1351219
TI  - Abortion.

PMID- 1351220
TI  - Abortion.

PMID- 1351221
TI  - European boards and colleges.

PMID- 1351222
TI  - NHS trusts and Jehovah's Witnesses.

PMID- 1351223
TI  - Overseas training and doctors from developing countries.

PMID- 1351224
TI  - Digit sucking.

PMID- 1351225
TI  - Diuretics and oedema: how to avoid rebound sodium retention.

PMID- 1351226
TI  - AIDS: the alternative view.

PMID- 1351227
TI  - AIDS: the alternative view.

PMID- 1351228
TI  - AIDS: the alternative view.

PMID- 1351229
TI  - HIV screening in Russia.

PMID- 1351230
TI  - Origin of AIDS.

PMID- 1351231
TI  - HIV-1 viraemia and influenza.

PMID- 1351232
TI  - Insulin autoimmune syndrome and HLA-DR4.

PMID- 1351233
TI  - Mazzotti test for onchocerciasis.

PMID- 1351234
TI  - Factor VIII and factor IX inhibitors in haemophiliacs.

PMID- 1351235
TI  - Factor VIII and factor IX inhibitors in haemophiliacs.

PMID- 1351236
TI  - Fatal pneumocystis pneumonia in asthmatic patient treated with methotrexate.

PMID- 1351237
TI  - Oesophageal candidosis in patients on high-dose inhaled steroids.

PMID- 1351238
TI  - Smoking and quinsy.

PMID- 1351240
TI  - Studies on the structure and function of the N-terminal domain of the
      pneumococcal murein hydrolases.
AB  - The structures of the choline-dependent pneumococcal murein hydrolases, LYTA
      amidase and CPL1 lysozyme, and the choline-independent CPL7 lysozyme were
      analysed by controlled proteolytic digestions. The trypsin cleavage of the CPL1
      and CPL7 lysozymes produced two resistant polypeptides, F1 and F7 respectively,
      corresponding to the N-terminal domain of the enzymes, whereas the amidase LYTA
      was completely hydrolysed by the protease. Interestingly, the F1 and F7 fragments
      showed a low, but significant, choline-independent lysozyme activity. Choline
      reduced the rate of proteolytic hydrolysis of choline-dependent enzymes,
      suggesting that the C-terminal choline-binding domain adopts a more resistant
      conformation in the presence of the ligand. On the other hand, the regions
      encoding the N-terminal domains of the three enzymes have been cloned and
      expressed in Escherichia coli, showing that these domains adopt an active
      conformation even in the absence of their C-terminal domains. The lower activity
      shown by the catalytic domains when compared with that of the complete enzymes
      suggests that the acquisition of a substrate-binding domain represents a
      noticeable evolutionary advantage for enzymes that interact with polymeric
      substrates, allowing them to achieve a higher catalytic efficiency. These results
      strongly reinforce the hypothesis that the pneumococcal murein hydrolases have
      been originated by fusion of two structural and functional independent domains,
      and provide new experimental support to the theory of modular evolution of
      proteins.

PMID- 1351239
TI  - [Epidemiological surveillance of infection by the human immunodeficiency virus
      (HIV) and of the acquired immunodeficiency syndrome (AIDS) in French Polynesia in
      1991].
AB  - The authors make out a statement about HIV infection in French Polynesia at the
      date of 1991 December 31. 96 cases all together of seropositive and AIDS infected
      people were recorded. These patients are young generally (78 p.c. between 21 and
      40 years old) sexually contaminated (72 out of 96) and live in Tahiti island (94
      p.c.). Sex-ratio is 2.8 male/1 female. Among them, we noted 55 p.c. of Europeans,
      38 p.c. of Polynesians and 7 p.c. of Asiatic people. Epidemiological monitoring
      of the infection was made easy because of a set of laws and possibilities of
      detection highly favourable. Progress of the infection is constant, with 20 new
      cases detected each year with a prevalence of 150 cases of AIDS per 1 million of
      inhabitants, French Polynesia could be classified as the 5th or 6th region of
      France as far as the importance of the disease. Clinical, biological and
      epidemiological taking of charge of patients is detailed as well as the
      prevention campaign.

PMID- 1351241
TI  - Isolation and characterization of conditional adherent and non-type 1 fimbriated
      Salmonella typhimurium mutants.
AB  - Mutations in the genes encoding the type 1 fimbriae of Salmonella typhimurium
      were isolated by selecting for the deletion of Tn10 inserted adjacent to the
      chromosomal fim+ genes and screening for the loss of mannose-sensitive
      haemagglutination (HA) activity. S. typhimurium strains with Tn10 insertions in
      ahp were hypersensitive to peroxides, and tetracycline-sensitive derivatives of
      ahp::Tn10 mutants displayed two fim mutant phenotypes. The predominant class of
      fim mutants did not synthesize type 1 fimbriae. A second type of fim mutant
      synthesized type 1 fimbriae and exhibited a conditional lipoic acid requirement
      for HA. A fim-lip conditional mutant synthesized type 1 fimbriae when grown in
      Mueller-Hinton broth but the haemagglutinating activity of the fimbriae was
      dependent upon the addition of lipoic acid to the growth medium. Independently
      isolated lip mutations did not demonstrate a similar pleiotropic effect on HA.
      Western blots of fimbriae extracted from a fim-lip conditional mutant that was
      grown under permissive and restrictive conditions indicated the presence of 33
      and 36.6 kDa proteins in HA+ fimbriae that were absent in HA- fimbriae. The HA+
      phenotype of both conditional and non-fimbriated mutants was restored by
      transformation with cloned genes encoding S. typhimurium type 1 fimbriae.

PMID- 1351242
TI  - The other mediator for adherence of Haemophilus influenzae organisms without
      involvement of fimbriae.
AB  - The number of the nontypeable Haemophilus influenzae (HiN) organisms that adhered
      to the primary mouse fetal lung cells was significantly more than type b
      Haemophilus influenzae (Hib) organisms. The average number of HiN organisms
      adherent to host cells was 2,291/100 host cells (range, 1,654-3,182), but that of
      Hib was markedly reduced to 147/100 host cells (range, 102-238). In this case, P
      value was less than 0.05 by using a paired Student t-test. The sonicated extract
      from HiN TMS11 organisms inhibited adherence of H. influenzae TMS11 organisms to
      monolayer at 76.3% and it inhibited adherence of Hib TMS24 organisms at 92.3%.
      This result indicates that a mediator existing on the surface of HiN organisms
      may be the same as that on type b organisms. The number of detected organisms in
      broncho and lung tissues 3 days after intranasal infection with HiN strains was
      significantly greater than that in infection with Hib strains. Therefore, in
      vitro adhesive capacity of H. influenzae organisms was correlative to infectivity
      by intranasal injection.

PMID- 1351243
TI  - Establishment of a mouse model of cystitis and roles of type 1 fimbriated
      Escherichia coli in its pathogenesis.
AB  - The role of type 1 fimbriae in promoting bladder colonization and the course of
      Escherichia coli cystitis were examined with type 1 fimbriated strains of
      clinically isolated E. coli. In the experiments of mice in vivo, intact bladder
      epithelium showed natural resistance to the adherence of type 1 fimbriated and
      non-fimbriated E. coli. However, the exfoliation of bladder superficial cells by
      trypsinization before the bacterial inoculation promoted the adhesion and
      colonization of type 1 fimbriated E. coli onto bladder epithelium. After
      colonization of E. coli, maximum numbers of E. coli and leukocytes were observed
      3 days after inoculation. Nine days after inoculation, both of E. coli and
      leukocytes disappeared and the regeneration of superficial cells was observed. On
      the other hand, superficial cells in mice injected with phosphate-buffered saline
      or non-fimbriated E. coli regenerated 5 days after trypsinization. The present
      study demonstrated that the removal of superficial cells is essential for the
      adhesion and colonization of type 1 fimbriated E. coli onto bladder epithelium in
      vivo and a new model of E. coli cystitis in mice was established. The model which
      we established is valuable for histopathological, immunological, and therapeutic
      studies.

PMID- 1351244
TI  - Depressed CD4/CD8 ratio in TPHA-negative patients with syphilis.
AB  - The Treponema pallidum hemagglutination assay (TPHA) is a widely used method for
      screening syphilis. We report our experience with six elderly (age 72.4 +/- 8.3
      years) patients with syphilis, whose TPHA was negative. Their cardiolipin (RPR)
      and absorbed fluorescence treponemal tests (FTA-ABS) were positive. TPHA-negative
      patients with syphilis were compared with TPHA-positive syphilitics by
      immunological analysis. We found that both the numbers and the percentage of CD4
      cells in TPHA-negative syphilitics were significantly lower than those in TPHA
      positive syphilitics (722 +/- 142 vs. 1,064 +/- 141/mm3, P less than 0.01: 35.1
      +/- 6.9 vs. 48.4 +/- 6.4%, P less than 0.01) and that the ratio of CD4 to CD8 was
      also lower in TPHA-negative syphilitics compared with TPHA-positive syphilitics
      (1.08 +/- 0.46 vs. 2.24 +/- 1.07, P less than 0.05). These data suggest that the
      TPHA is insufficient for excluding elderly syphilitics because of immunological
      impairment seen in aged patients.

PMID- 1351246
TI  - The R1 gene conferring race-specific resistance to Phytophthora infestans in
      potato is located on potato chromosome V.
AB  - Late blight in potato is caused by the fungus Phytophthora infestans and can
      inflict severe damage on the potato crop. Resistance to P. infestans is either
      based on major dominant R genes conferring vertical, race-specific resistance or
      on "minor" genes inducing horizontal, unspecific resistance. A dihaploid potato
      line was identified which carried the R1 gene, conferring vertical resistance to
      all P. infestans races, with the exception of those homozygous for the recessive
      virulence allele of the locus V1. The F1 progeny of a cross between this
      resistant parent P(R1) and P(r), a line susceptible to all races, was analysed
      for segregation of R1 and of restriction fragment length polymorphism (RFLP)
      markers distributed on the potato RFLP map comprising more than 300 loci. The R1
      locus was mapped to chromosome V in the interval between RFLP markers GP21 and
      GP179. The map position of R1 was found to be very similar to the one of Rx2, a
      dominant locus inducing extreme resistance to potato virus X.

PMID- 1351245
TI  - Construction of a yeast artificial chromosome library of tomato and
      identification of cloned segments linked to two disease resistance loci.
AB  - We have constructed a yeast artificial chromosome (YAC) library of tomato for
      chromosome walking that contains the equivalent of three haploid genomes (22,000
      clones). The source of high molecular weight DNA was leaf protoplasts from the
      tomato cultivars VFNT cherry and Rio Grande-PtoR, which together contain loci
      encoding resistance to six pathogens of tomato. Approximately 11,000 YACs have
      been screened with RFLP markers that cosegregate with Tm-2a and Pto - loci
      conferring resistance to tobacco mosaic virus and Pseudomonas syringae pv.
      tomato, respectively. Five YACs were identified that hybridized to the markers
      and are therefore starting points for chromosome walks to these genes. A subset
      of the library was characterized for the presence of various repetitive sequences
      and YACs were identified that carried TGRI, a repeat clustered near the telomeres
      of most tomato chromosomes, TGRII, an interspersed repeat, and TGRIII, a repeat
      that occurs primarily at centromeric sites. Evaluation of the library for
      organellar sequences revealed that approximately 10% of the clones contain
      chloroplast sequences. Many of these YAC clones appear to contain the entire 155
      kb tomato chloroplast genome. The tomato cultivars used in the library
      construction, in addition to carrying various disease resistance genes, also
      contain the wild-type alleles corresponding to most recessive mutations that have
      been mapped by classical linkage analysis. Thus, in addition to its utility for
      physical mapping and genome studies, this library should be useful for chromosome
      walking to genes corresponding to virtually any phenotype that can be scored in a
      segregating population.

PMID- 1351248
TI  - Second International Congress of Movement Disorders. Munich, Germany, June 24-26,
      1992. Abstracts.

PMID- 1351247
TI  - [Enzyme activity in serum of healthy newborn infants. Normal values of CPK, gamma
      GT, GOT, GLDH. LAP, LDH and HBDH in the first 144 hours of life].
AB  - QUESTION: There are no available enzyme determinations for the neonatal period
      taking in account the considerable changes during the first hours of life.
      Moreover, in former studies the number of probands has been small and no
      standardized and optimized methods have been used for the determinations. It was
      the aim of the presented study to evaluate reference ranges for these enzymes in
      healthy newborns for the first week of life. METHODS: We realized a controlled
      prospective study about the serum activities of CPK, GGT, GOT, GLDH, LAP, LDH,
      and HBDH in healthy newborns (n = 87). The enzyme determinations were done for
      the first time in a serial manner at five fixed times: post partum (cord), 12,
      24, 72, and 144 hours post partum with optimized test-kits. RESULTS: The
      evaluated serum enzyme activities are stated with median, 25th, and 75th
      percentile by rank. We propose these results as reference ranges for these enzyme
      activities during the first 144 hours of life. CONCLUSION: For the first time
      reference ranges for serum enzyme activities concerning the striking activity
      changes during the first hours of life are evaluated for healthy newborn infants.
      These results enable comparative investigations in the case of newborn diseases.

PMID- 1351249
TI  - Chemotherapy of metastatic melanoma.

PMID- 1351250
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 28-1992. A 45-year-old man with confusion, seizures, and few
      focal findings.

PMID- 1351252
TI  - Retraction brain ischaemia: cerebral blood flow, evoked potentials, hypotension
      and hyperventilation in a new animal model.
AB  - Undue intraoperative brain retraction can cause significant neurosurgical
      morbidity. By combining brain retractor blade pressure measurement with
      monitoring of brain electrical activity, one can determine the limits of safe
      brain retraction and then test systematically various therapeutic interventions.
      Cortical evoked potential (EP) mapping and laser-Doppler cerebral blood flow
      (CBF) measurement were undertaken during brain retraction in the miniature swine
      (Sus scrofa). Forelimb somatosensory EP recording during subtemporal retraction
      simulated the pterional and subtemporal approaches, respectively. Retraction
      pressure of 30 mmHg usually resulted in a 50% decrement in EP amplitude after 10
      to 20 minutes in normotensive, normocapnic adult animals. Recovery of EP occurred
      within 5 to 10 minutes of retraction release. The effects of animal age, induced
      hypotension (nitroprusside, MAP approximately 40), and induced hypocapnia
      (hyperventilation, PaCO2 approximately 28) on EP preservation during retraction
      were then investigated, with data reported here from 23 animals (8 to 35 kg). By
      Spearman rank correlation coefficients, early loss of EP was associated with the
      following: lower MAP (p approximately 0.0001), lower CBF (p approximately
      0.0005), lower PaCO2 (p less than 0.001), and older age (p approximately 0.01).
      These results indicate (1) retractors should be relaxed every 10-15 minutes
      whenever possible (for at least 5 minutes), and (2) hypotension, in particular,
      but also hypocapnia (hyperventilation) should not be used indiscriminately.
      Details of this new model of retraction ischaemia are presented.

PMID- 1351251
TI  - Differential sensitivity of cholinergic and GABAergic neurons in chick embryos
      treated intracerebrally with ethanol at 8 days of embryonic age.
AB  - We have shown that in embryos treated with ethanol in ovo during days 1-3, a
      critical period of neuroembryogenesis, cholinergic neuronal phenotypic expression
      is decreased whereas GABAergic and catecholaminergic neuronal populations are
      increased as assessed by neuronal markers choline acetyltransferase (ChAT),
      glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH) respectively. In
      this study, ethanol was administered intracerebrally to embryos at embryonic day
      8, embryos were sacrificed at day 9 and ChAT and GAD activities assayed
      separately in cerebral hemispheres and remaining brain (diencephalon-midbrain and
      optic lobes). We found that ChAT activity was enhanced in the cerebral
      hemispheres only, whereas GAD activity was decreased in both cerebral hemispheres
      and remaining brain. We have concluded that the differential responses of
      neuronal phenotypes to ethanol may reflect compensatory mechanisms to ethanol
      insult. Moreover, these findings emphasize the vulnerability of the GABAergic
      neuronal phenotypes to ethanol neurotoxicity during early brain development in
      the chick.

PMID- 1351253
TI  - Retraction brain ischaemia: mannitol plus nimodipine preserves both cerebral
      blood flow and evoked potentials during normoventilation and hyperventilation.
AB  - In our miniature swine model simulating operating room brain retraction, we
      investigated the effects of mannitol plus nimodipine on cerebral blood flow (CBF)
      and evoked potentials (EP) ipsilateral and contralateral to retraction, in
      comparison with either agent alone, during both normoventilation and
      hyperventilation. We here report results in 27 animals with intravenous mannitol
      (2 g kg-1 over 15 min) and/or nimodipine (1 microgram kg-1 min-1 constant
      infusion). Mannitol plus nimodipine was superior both to controls and to either
      mannitol alone or nimodipine alone in preserving EP amplitude ipsilateral to
      retraction during both normoventilation and hyperventilation. Mannitol alone was
      effective in normoventilation at preserving EP, while nimodipine alone was
      effective in hyperventilation. No significant asymmetries in CBF or EP were seen
      with mannitol plus nimodipine in either normoventilation or hyperventilation. By
      five minutes postretraction CBF had returned to preretraction values for all
      groups, and EP amplitude had returned also except for hyperventilated controls.
      In this model of brain retraction, mannitol plus nimodipine is superior to either
      agent alone in maintaining both CBF and EP when normoventilation and
      hyperventilation are employed. The results are discussed in terms of the possible
      mechanisms for the different and complementary effects of mannitol and
      nimodipine.

PMID- 1351254
TI  - New trend in neuroscience: low-power laser effect on peripheral and central
      nervous system (basic science, preclinical and clinical studies).
AB  - The present review summarizes findings in our continuing study of the use of low
      power laser irradiation (LPLI) in the treatment of severely injured peripheral
      (PNS) and central nervous systems (CNS). The radiation method was proposed by
      Rochkind and has been modified over the last 13 years. LPLI in specific
      wavelengths and energy density maintains the electrophysiological activity of
      severely injured peripheral nerve in rats, preventing scar formation (at injury
      site) as well as degenerative changes in the corresponding motor neurons of the
      spinal cord, thus accelerating regeneration of the injured nerve. Laser
      irradiation applied to the spinal cord of dogs following severe spinal cord
      injury and implantation of a segment of the peripheral nerve into the injured
      area diminished glial scar formation, induced axonal sprouting in the injured
      area and restoration of locomotor function. The use of laser irradiation in
      mammalian CNS transplantation shows that laser therapy prevents extensive glial
      scar formation (a limiting factor in CNS regeneration) between a neural
      transplant and the host brain or spinal cord. Abundant capillaries developed in
      the laser-irradiated transplants, and was of crucial importance in their
      survival. Intraoperative clinical use of laser therapy following surgical
      treatment of the tethered spinal cord (resulting from myelomeningocele,
      lipomyelomeningocele, thickened filum terminale or fibrous scar) increases
      functional activity of the irradiated spinal cord. In a previous experimental
      work, we showed that direct laser treatment on nerve tissue promotes restoration
      of the electrophysiological activity of the severely injured peripheral nerve,
      prevents degenerative changes in neurons of the spinal cord and induces
      proliferation of astrocytes and oligodendrocytes. This suggested a higher
      metabolism in neurons and improved ability for myelin production under the
      influence of laser treatment. The tethering of the spinal cord causes mechanical
      damage to neuronal cell membranes leading to metabolic disturbances in the
      neurons. For this reason, we believe that using LPLI may improve neuronal
      metabolism, prevent neuronal degeneration and promote improved spinal cord
      function and repair. The possible mechanism of LPLI is investigated. Using
      electron paramagnetic resonance in cell culture models, we found that at low
      radiation doses, singlet oxygen is produced by energy transfer from porphyrin
      (not cytochrome as commonly assumed) which is known to be present in the cell. At
      low concentration, singlet oxygen can modulate biochemical processes taking place
      in the cell and trigger accelerated cell division. On the other hand, at high
      concentration, singlet oxygen damages the cell.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1351255
TI  - Changes of superoxide dismutase activity and ascorbic acid in focal cerebral
      ischaemia in rats.
AB  - Free radical reactions are supposed to cause ischaemic brain damage, and active
      oxygens can initiate these chains reaction. If active oxygens play important
      roles in ischaemic brain damage, the activity of superoxide dismutase, scavenger
      of superoxide anion, is supposed to decrease in ischaemic brain. The reduced form
      of ascorbic acid also scavenges superoxide anion. In rat middle cerebral artery
      focal ischaemia, we investigated the changes in superoxide dismutase activity and
      the concentration of reduced ascorbate up to 48 hours. Middle cerebral artery
      territory of each cerebral hemisphere was homogenized. The supernatant was
      divided into two aliquots; one was dialysed to remove ascorbate and the other was
      not. The enzyme activity of the dialysed specimen from the ischaemic hemisphere
      did not decrease within 4 h after the arterial occlusion. The activity of the
      dialysed specimen from the nonischaemic side remained unchanged during the
      examination. Reduced ascorbate levels in nondialysed samples showed similar
      changes to the superoxide dismutase activities in the dialysed samples. Our data
      suggest that ascorbic acid may exert the enzyme activity and that the enzyme
      activity remains at the normal level in the early phase of ischaemia despite the
      irreversible ischaemic changes that take place within 4 h after the onset of
      ischaemia.

PMID- 1351256
TI  - CBF and transcranial Doppler sonography during vasodilatory stress tests in
      patients with common carotid artery occlusion.
AB  - Cerebral blood flow (CBF) and the cerebral vasoreactivity was measured in
      patients with cerebrovascular disease and longstanding occlusion of the common
      carotid artery (CCA). In addition, regional CBF was correlated with transcranial
      doppler (TCD) measurements at baseline and during 6% CO2 inhalation and after
      intravenous administration of 1 g of acetazolamide. Twelve patients with a mean
      age of 62 years (range 45 to 71 years) were included, and the data compared to
      age-matched healthy controls. CBF was measured by intravenous injection of xenon
      133 and SPECT (Tomomatic 564). TCD of the middle cerebral artery (MCA) was done
      by EME TC-64B. A very low global CBF value of 28 +/- 5 (SD) ml 100 g-1 min-1 was
      found at baseline as compared to 55 +/- 5 ml 100 g-1 min-1 in the normal
      controls. During 6% CO2-inhalation and after acetazolamide administration, CBF
      increased by 58 +/- 24% and 51 +/- 21%, respectively, indicating substantial
      collateral supply. Correlative analysis of CBF in the MCA territory and TCD in
      the MCA showed statistical significance only for the pooled data, i.e. compiling
      the data obtained during baseline and the two vasodilatory tests, and then only
      for the mean and peak TCD velocity (e.g. r = 0.59, p less than 0.002, n = 35,
      mean velocity, right side). We conclude that TCD measurements do not predict
      regional CBF in patients with CCA occlusion. The study emphasizes that these two
      methods yield supplementary information, with TCD measurements providing
      information of the circle of Willis and CBF studies of the flow distribution.

PMID- 1351257
TI  - Loss of heterozygosity on the short arm of chromosome 17 in human astrocytomas.
AB  - Using restriction fragment length polymorphism (RFLP) analysis, we demonstrated
      in 4 of 20 patients with astrocytomas loss of heterozygosity on the short arm of
      chromosome 17 (17p), in the telomeric segment distal to DNA marker pEW301 (locus
      D17S58). The loss of heterozygosity may uncover a mutation in a tumour suppressor
      gene and thus lead to or permit tumour formation. The p53 tumour suppressor gene,
      which is localized at 17p13, is a likely candidate for the tumour suppressor gene
      involved. Of the 4 patients with loss of heterozygosity on 17p, one patient had a
      grade I astrocytoma, another patient had a grade II astrocytoma and 2 patients
      had glioblastoma multiforme. Since the loss of heterozygosity on 17p was detected
      in low-grade as well as in high-grade astrocytomas, it is possible that p53
      suppressor gene loss may be an early genetic event in the multistep process of
      astrocytoma formation.

PMID- 1351258
TI  - Cross-resistance pattern in brain tumour cells resistant to antitumour
      chloroethylnitrosoureas.
AB  - We tested acquired resistance and cross-resistance of brain tumour cells after
      repeated treatments of antitumour agents including chloroethylnitrosoureas
      (CENUs) in clinical use for brain tumour chemotherapy. Within ten repeated 2-day
      incubation periods with either 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2
      chloroethyl)-3-nitrosourea hydrochloride (ACNU) or methyl-6-[3-(2-chloroethyl)-3
      nitrosoureido]-6-deoxy-alpha-D-glucopyr anoside (MCNU), brain tumour cells (9L)
      developed high degrees of resistance to these drugs, as evidenced by about 3- and
      6-fold increases, respectively, at the 10% survival dose (SD10). The resistance
      has unchanged with time after termination of challenging treatments. Repeated
      challenges with bleomycin (BLM), cis-diaminedichloroplatinum (II) (CDDP), and
      methotrexate (MTX) did not develop a significant resistance. ACNU-resistant
      (9L/ACNU) cells showed complete cross-resistance to MCNU, and MCNU-resistant
      (9L/MCNU) cells to ACNU. Drug sensitivity to other DNA-damaging agents (BLM, NCS,
      CDDP, etoposide) than CENUs fluctuated to a lesser extent among 9L parent,
      9L/ACNU, and 9L/MCNU cells. These data suggest clinical disadvantage of prolonged
      adjuvant CENU chemotherapy and advantage of combined CENU chemotherapy with other
      agents than CENUs in brain tumours.

PMID- 1351259
TI  - Efficacy of the 21-aminosteroid U74006F in improving neurological recovery after
      spinal cord injury in rats.
AB  - The efficacy of three different regimens of the 21-aminosteroid U74006F in
      counteracting the neurological damage after spinal cord compression causing
      paraparesis in rats was investigated. Three groups of ten animals each were given
      totally 6 mg/kg of U74006F in different regimens beginning one hour after injury
      (A: bolus doses of 1.5 mg/kg at 1, 4, 7 and 10 hours; B: bolus of 1.5 mg/kg at 1
      hour and 4.5 mg/kg as an infusion over the next 9 hours; and C: infusion alone, 6
      mg/kg, given between 1 and 10 hours after trauma). Two groups of ten animals each
      received vehicle alone in administration modes comparable to those of the U74006F
      treated animals. The motor function was assessed daily on the inclined plane. On
      day one, the capacity angle had decreased from about 62 degrees preoperatively to
      28-30 degrees in the two vehicle-treated groups and in group C. In these groups
      there was a similar improvement in neurological function and on day 9 the
      capacity angles were 49-55 degrees. In groups A and B, both of which received a
      bolus dose of U74006F at 1 hour, the neurological outcome improved on day one
      with capacity angles of 38-40 degrees. The difference in neurological function
      between the animals given U74006F as bolus doses and those given vehicle alone
      persisted over the entire observation span until day 9. The data suggest that
      early treatment with a bolus dose seems to be required in order to obtain an
      effect of U74006F on neurological recovery.

PMID- 1351260
TI  - In vitro evidence supporting two mechanisms of action for the anion transport
      inhibitor L-644,711 in cerebral ischaemia.
AB  - L-644,711 is a novel anion channel inhibitor which has previously been shown to
      decrease brain injury in two related rabbit models of cerebral ischaemia. We
      hypothesize two mechanisms of action of L-644,711 for its salutary effects on
      cerebral ischaemia: inhibition of neutrophil function and prevention of
      excitotoxin release from astrocytes. We present in vitro evidence supporting
      these two mechanisms of action. L-644,711 demonstrated a dose dependent
      inhibition of fMLP-induced neutrophil aggregation and superoxide anion release.
      In addition, L-644,711 demonstrated a dose dependent inhibition of glutamate
      release from swollen astrocytes in primary culture. We conclude that L-644,711
      may prevent brain injury in cerebral ischaemia by inhibiting neutrophil function
      and preventing release of glutamate from swollen astrocytes.

PMID- 1351261
TI  - Reversal of epileptic state by patterned electrical stimulation suggested by
      trion model calculations.
AB  - The trion model is based on the Mountcastle columnar organizational principle of
      cortex. A trion represents an idealized minicolumn with three levels of firing
      activity and is highly structured in time and in spatial connections. A network
      of trions has a large repertoire of quasi-stable, periodic spatial-temporal
      firing patterns, MPs, which can be excited and each MP can be readily enhanced by
      a Hebb learning rule. A particular MP present in most repertoires has all trions
      firing together in synchrony, which we identify as the 'Epileptic' MP (EMP). In
      trion model simulations, the EMP can be enhanced via the Hebb rule after
      electrical stimulation so that an epileptic focus with after discharge (about 3-6
      Hz) is formed and spontaneous firing of the EMP occurs (as in kindling).
      Following this, by using a small array of closely-spaced stimulating electrodes
      out of phase, other MPs are enhanced via the Hebb rule eliminating the dominance
      of the EMP. We strongly urge that these predictions be tested in the animal
      models for possible clinical relevance.

PMID- 1351262
TI  - Single optical fibre transducer for pressure measurement.
AB  - In a single optical fibre transducer, light is injected into a fibre through a
      fibre optic coupler, located at some distance from the distal end of the fibre.
      Injected light travels toward the front face of the fibre, where it exits in the
      shape of a cone. then, after reflection from a reflective surface, it is
      readmitted into the same fibre. The reflected beam of light travels back through
      the coupler, exits through the distal end of the fibre and illuminates the
      photosensitive area of a photo diode, where it is converted to an electrical
      current. Depending on which one of the parameters is allowed to vary the amount
      of the returning light, one can build a variety of different sensors. Among them
      are: linear/angular displacement sensors and their derivatives such as pressure
      or force sensors; transmittance sensors such as turbidity and chemical sensors;
      reflectance sensors such as temperature sensors, optical encoders and scanners,
      colourometric and other types of chemical sensors. In the case of the single
      optic fibre transducer (SOFT) made by Pearl Instruments (Chicago, II, USA), the
      reflective surface is made of a thin metal foil with 6 microns thickness and 1.25
      mm diameter. Optical fibres are pf the multimode type with 55 microns diameter.
      Their numerical aperture is equal to 0.66. The SOFT head is 1.25 mm in diameter
      and has an overall length of 50 cm. The disposable part of the system contains
      the head, fibre, protective sheathing and plug. Its operating range is -15 to
      +300 mmHg, and +25 to +45 degrees C, and its resolution is +/- 1 mmHg.

PMID- 1351263
TI  - Neurodevelopment in late infancy after prenatal exposure to benzodiazepines--a
      prospective study.
AB  - Growth and neurodevelopment at 6, 10 and 18 months of age have been studied
      prospectively and longitudinally in a series of 17 children born to mothers who
      used benzodiazepines (BZD) in therapeutic doses as their only psychotropic drug
      throughout pregnancy. The results were compared with a group of 29 children born
      to mothers without any known use of psychotropic drugs. The BZD-exposed children
      caught up their low mean birth-weight, at an early stage, whereas the slightly
      decreased head circumference at birth remained at the same low level. In five
      infants, a pattern of craniofacial anomalies was found. Deviating
      neurodevelopmental and clinical symptoms and signs were common. The gross motor
      development was retarded at 6 and 10 months, but was nearly normal at 18 months.
      Impaired fine motor functions were found on all follow-up occasions. At 18
      months, the most prominent finding was a delayed development of pincer grasp. The
      BZD-exposed children showed deviations in muscle tone and pattern of movements
      more frequently than children in the reference group. The study suggests that the
      use of BZD in therapeutic doses throughout pregnancy can have negative effects on
      the development of children up to 18 months of age. The long-term hazards cannot
      be evaluated from these results. A further follow-up at early school age is
      needed and is in progress.

PMID- 1351264
TI  - Hypothalamic-pituitary-adrenal axis function in chronic schizophrenia:
      association with clinical features.
AB  - The function of the hypothalamic-pituitary-adrenal axis (HPA-axis) and its
      association with clinical features in chronic schizophrenia were investigated.
      Twenty of 33 chronic schizophrenics exhibited an abnormal diurnal variation of
      the saliva cortisol level. The patients with abnormal diurnal variation gave
      higher scores for some negative symptoms than those with normal diurnal
      variation. On the dexamethasone suppression test (DST) of saliva samples, 13 of
      34 chronic schizophrenics were abnormal. The patients with DST nonsuppression
      were more frequently classified into disorganized type and exhibited low scores
      of anxiety compared with the patients with normal suppression. The 9 patients who
      showed abnormal diurnal variation and DST nonsuppression were more frequently
      classified into disorganized type and showed higher scores of negative symptoms
      than the 9 patients who did not show any abnormal cortisol data. These results
      suggest that there might be some disturbance in the function of the HPA-axis in a
      group of chronic schizophrenics and that these patients might have severe
      negative symptoms.

PMID- 1351265
TI  - Effects of sulpiride and oxypertine on the dopaminergic system in the rat
      striatum.
AB  - We have examined the effects of sulpiride, oxypertine and haloperidol on the
      behavioral and biochemical dopamine receptor function in the rat striatum.
      Although acute treatment with haloperidol or oxypertine induced catalepsy,
      tolerance to catalepsy developed following chronic treatment with haloperidol but
      not with oxypertine. Rats treated with acute or chronic sulpiride did not show
      signs of catalepsy. Intracerebroventricular administration of sulpiride, however,
      induced catalepsy and tolerance developed after chronic treatment. After chronic
      treatment with either of these three drugs, dopamine D2 receptors were up
      regulated in the striatum. While acute administration of haloperidol, sulpiride
      or oxypertine increased the concentration of homovanillic acid in the striatum,
      the rate of increases was attenuated following chronic treatment with haloperidol
      or sulpiride, but not with oxypertine. While acute administration of sulpiride or
      oxypertine decreased dopamine, the decrease was attenuated following repeated
      administration of sulpiride but not of oxypertine. These results suggest that the
      unique pharmacological profile of oxypertine may be related to its therapeutic
      effect of activating apathetic patients, and that both sulpiride and oxypertine
      may cause tardive dyskinesia, as haloperidol does.

PMID- 1351266
TI  - Persisting modification of dendritic calcium influx by excitatory amino acid
      stimulation in isolated Ca1 neurons.
AB  - Spatiotemporal changes of the intracellular calcium ion (Ca2+) were recorded by
      digital ratio imaging of fura-2 in pyramidal neurons acutely isolated from the
      adult guinea-pig hippocampus. Increases in calcium were evoked in tetrodotoxin (2
      microM) containing saline either by stimulation with the excitatory amino acids,
      glutamate or N-methyl-D-aspartate, or by depolarization with high potassium (50
      mM). Local stimulation with excitatory amino acids, applied from a microelectrode
      with 1-2-s iontophoretic pulses at the dendrite, induced a rapid increase in
      intracellular Ca2+ predominantly supported by a Ca2+ influx at the site of
      stimulation (primary response). Ca2+ levels recovered within 1-2 min in about one
      half of the neurons examined. In the remaining neurons the initial exposure to
      excitatory amino acids induced a non-recovering gradient of Ca2+, highest at the
      site of stimulation, that lasted for periods of minutes (secondary response).
      Within the population that showed recovery from the initial agonist exposure, a
      second, or in some cases, a third application triggered the sustained, secondary
      response. Pretreatment of neurons with the protein kinase inhibitor sphingosine
      (10 microM) blocked development of the secondary response but had no effect on
      the primary response to the excitatory amino acids. There were no Ca2+ increases
      in Ca(2+)-free medium with either agonist, and responses to N-methyl-D-aspartate
      were blocked by 2-amino-4-phosphovaleric acid and significantly reduced at
      physiological concentrations of Mg2+ (1.8 mM). The maintained gradient of Ca2+
      was supported by a continuous influx of calcium from outside the cell. In
      contrast, dendritic gradients of Ca2+ induced by short exposures to high
      potassium (50 mM, 5 s) collapsed immediately at the end of the stimulus and could
      be repeatedly evoked. Minute-long exposures to high K, induced large, repeatable
      changes in Ca2+ but there was always rapid recovery in normal saline. K
      depolarization applied after excitatory amino acid stimulation produced larger
      Ca2+ changes than the same K stimulus applied before the cell was stimulated with
      the excitatory amino acid. Bath application of GABA (10-100 microM) reduced the
      magnitude of the maintained Ca2+ gradients. The functional significance of the
      extended, secondary response cannot be directly established from these
      measurements on isolated neurons, but its properties could give rise, in part, to
      mechanisms involved in neural plasticity, in kindling epileptogenesis or in
      glutamate-induced toxicity.

PMID- 1351267
TI  - Selective vulnerability of hippocampal CA1 neurons cannot be explained in terms
      of an increase in glutamate concentration during ischemia in the gerbil: brain
      microdialysis study.
AB  - Ischemia-induced selective neuronal injury to field CA1 is not attributable to
      selective glutamate release in field CA1 during ischemia. Excessive release of
      glutamate has been proposed to play a major role in ischemia-induced selective
      neuronal death in field CA1 of the hippocampus. It is well known that, following
      carotid arterial occlusion of 5 min duration in the gerbil, the pyramidal neurons
      in field CA1 show delayed neuronal death, whereas the neurons in field CA3 do not
      show any neuronal degeneration. In the present study, we measured the levels of
      released glutamate during ischemia in field CA1 and field CA3, separately, and
      evaluated whether there are subregional differences in the concentration of
      released glutamate which could be a satisfactory explanation for the selective
      vulnerability of hippocampal neurons to ischemia. Extracellular glutamate levels
      were significantly increased during ischemia in both field CA1 and field CA3. No
      significant differences were detected in the time-course of change in glutamate
      release and the levels of glutamate between field CA1 and field CA3. This result
      indicates that the increased glutamate levels do not play a pivotal part in the
      detrimental effect of glutamate during 5-min ischemia. Some differentiated post
      synaptic organization may act as a crucial factor in the development of ischemia
      induced selective neuronal death in the gerbil hippocampus.

PMID- 1351268
TI  - Inhibition of noradrenergic locus coeruleus neurons by C1 adrenergic cells in the
      rostral ventral medulla.
AB  - Recent anatomical and physiological experiments indicate that the nucleus locus
      coeruleus receives a predominant excitatory amino acid input, as well as a
      substantial inhibitory input, from the nucleus paragigantocellularis in the
      ventrolateral medulla. To determine whether C1 adrenergic neurons are involved in
      the inhibitory projection, the effects of the alpha-2 adrenoceptor antagonist,
      idazoxan, on inhibitory responses of locus coeruleus neurons to
      paragigantocellularis stimulation were characterized in the rat. Intravenous
      administration of idazoxan (0.2-1 mg/kg) attenuated paragigantocellularis-evoked
      inhibition, and often revealed an underlying weak excitation. Intraventricular
      administration of kynurenate, an excitatory amino acid antagonist, eliminated
      excitation from paragigantocellularis and disclosed an underlying inhibitory
      response in many locus coeruleus neurons that were previously excited by
      paragigantocellularis stimulation. These results revealed that about 90% of locus
      coeruleus neurons receive inhibition from the paragigantocellularis. Intravenous
      idazoxan significantly reduced such paragigantocellularis-evoked inhibition,
      completely blocking this response in three of eight locus coeruleus cells tested.
      Idazoxan was much more potent when locally infused into the locus coeruleus.
      Local infusion of idazoxan (0.1-2.5 ng) into locus coeruleus produced a dose
      dependent decrease of paragigantocellularis-evoked inhibition and completely
      blocked the inhibition in 10/33 locus coeruleus neurons, indicating that the site
      of idazoxan action was in the locus coeruleus. These results extend our previous
      anatomical studies of adrenergic input to locus coeruleus, and indicate that C1
      adrenergic neurons in the paragigantocellularis provide a direct inhibitory input
      to the great majority of locus coeruleus noradrenergic neurons. In addition, this
      is the first report of a neuronal response to activation of C1 adrenergic cells
      indicating that these neurons are strongly inhibitory when acting at alpha-2
      receptors in vivo.

PMID- 1351270
TI  - A critical review of the afferent pathways and the potential chemical mediators
      involved in cardiac pain.
AB  - There is considerable evidence that on the anterior surface of the heart (which
      is usually supplied by the left anterior descending and the proximal part of the
      left circumflex coronary arteries), sympathetic efferent reflexes characterized
      by tachycardia and/or hypertension predominate following experimental or
      pathological perturbations. These cardiovascular reflexes are accompanied by an
      increase in presumed nociceptive afferent traffic and, in pathological condition,
      by pain. In these experiments, there is generally no effect of vagotomy on
      afferent nerve traffic, and lower cervical and upper thoracic sympathectomies
      help provide relief from angina. On the other hand, experimental or pathological
      perturbations involving the inferior-posterior surface of the heart (supplied by
      the right and distal parts of the left circumflex coronary arteries), are
      characterized by vagal efferent reflexes, resulting in bradycardia and/or
      hypotension. These reflexes are accompanied by an increase in vagal afferent
      nerve traffic and, in pathological conditions, by pain. In these experiments,
      vagotomy generally abolishes such cardiovascular reflexes, and lower cervical and
      upper thoracic sympathectomies are not effective in the relief from angina.
      Although cardiac sympathetic afferents are unquestionably involved in the central
      transmission of nociceptive information from the heart, it is also likely that
      there is a contributing role from the vagus in cardiac pain. It is important
      experimentally to understand the natural stimulus that gives rise to angina. In
      the clinical situation, a decrease in coronary blood flow or an increase in the
      metabolic demands of the myocardium due to increased work are obvious
      precipitating factors which lead to myocardial ischemia. In the experimental
      situation, occlusion of the coronary arteries is often used as a stimulus which
      mimics myocardial ischemia. As people who frequently experience angina have
      varying degrees of coronary artery disease, it is difficult to accept that the
      state of the coronary arteries of the normal experimental animal bear any
      resemblance to the state of the coronary arteries under pathological conditions.
      That is, the gain of homeostatic reflexes, the basal concentrations of
      neuroactive substances in the plasma, the myocardium and the afferent terminals,
      the excitability of the afferents, access of chemical mediators (e.g. bradykinin,
      5-HT, adenosine, histamine, prostaglandins, potassium, lactate), to afferents,
      and the overall function of the animal are all significantly different. We have
      no idea how control mechanisms have been altered in the person with severe
      coronary artery disease compared to the normal patient or the "normal"
      experimental animal.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1351269
TI  - Serotonin1A facilitation of frog motoneuron responses to afferent stimuli and to
      N-methyl-D-aspartate.
AB  - The effects of serotonin and excitatory amino acids on motoneurons were examined
      by sucrose gap recordings from the ventral root of the isolated, hemisected frog
      spinal cord superfused with magnesium-free, carbonate-buffered Ringer solution.
      Low concentrations of serotonin (0.1 microM) and the serotonin1A agonist 8
      hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT; 0.01 microM) significantly
      increased the duration and amplitude of the polysynaptic components of ventral
      root potentials produced by dorsal root stimulation. The facilitations of the
      ventral root potentials were blocked by the serotonin1A antagonist spiroxatrine,
      but were unaffected by the serotonin2 antagonist ketanserin or the serotonin3
      antagonist 1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,-dichlorobenzoate (MDL
      72222). The actions of 0.1 microM serotonin on motoneuron depolarizations evoked
      by the putative excitatory amino acid transmitters L-glutamate and L-aspartate
      were quite variable, but in the presence of ketanserin (20 microM), small
      consistent increases in amino acid-induced motoneuron depolarizations were
      observed. 8-OH-DPAT significantly enhanced motoneuron depolarizations elicited by
      the selective excitatory amino acid agonist N-methyl-D-aspartate in both normal
      and tetrodotoxin-containing Ringer solution. Quisqualate-induced motoneuron
      depolarizations were also facilitated by 8-OH-DPAT in normal Ringer solution, but
      these increases were eliminated by addition of either tetrodotoxin or the N
      methyl-D-aspartate antagonist D(-)-2-amino-5-phosphonovalerate to the Ringer
      superfusate. Kainate-depolarizations were not altered by low concentrations of
      serotonin or 8-OH-DPAT. Prior exposure of the cord to spiperone, but not
      ketanserin or MDL 72222 blocked the enhancement of N-methyl-D-aspartate-induced
      motoneuron depolarizations by 8-OH-DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351271
TI  - Functionally distinct subpopulations of striatal neurons are differentially
      regulated by GABAergic and dopaminergic inputs--II. In vitro analysis.
AB  - In the companion report [Nisenbaum and Berger (1992) Neuroscience 48, 561-578]
      the contrasting paired impulse responses to stimulation of the corticostriatal
      pathway which define the Type I and Type II subpopulations of striatal neurons
      were shown to reflect differential regulation by GABAergic and dopaminergic
      inputs. More specifically, the decreased probability of spike discharge
      (inhibition) to long interstimulus intervals (60-260 ms) characteristic of Type I
      neurons was found to be dependent on dopaminergic input via D1 receptor
      activation, whereas the inhibition to short interstimulus intervals (10-20 ms)
      distinctive of Type II neurons was found to be mediated by GABAergic input acting
      through GABAA receptor stimulation. The present experiments have further
      investigated the contribution of GABAergic and dopaminergic feedforward and/or
      feedback circuits to the functional identities of Type I and Type II neurons
      using an in vitro corticostriatal slice preparation. In this preparation, the
      cortical afferents to the striatum are preserved, allowing for activation of
      striatal cells in a manner similar to that used in vivo; however, all axons
      arising from midbrain and brainstem structures including the substantia nigra are
      transected, and intrastriatal GABAergic pathways are reduced. Consistent with the
      predicted effect of disrupting these two neurotransmitter pathways, the paired
      impulse responses of striatal neurons recorded in vitro were not similar to the
      responses of either Type I or Type II neurons recorded in vivo. Indeed, the
      paired impulse profiles of striatal neurons recorded in vitro were relatively
      homogeneous in that virtually all cells displayed an increased probability of
      spike discharge (facilitation) to the second impulse of all interstimulus
      intervals (10-500ms) tested. Low concentrations of allosteric agonists for the
      GABAA receptor, pregnanolone (5 microM) and pentobarbital (50 microM),
      selectively inhibited spike discharge in response to short interstimulus
      intervals (10-20 ms) for approximately 40% of the neurons sampled, but produced
      no change in facilitation to longer interstimulus intervals (30-500 ms). The
      agonist-induced inhibition to short interstimulus intervals was blocked by
      bicuculline (10-20 microM), and was not mimicked by the GABAB receptor agonist,
      baclofen (1-5 microM). In addition, application of dopamine (5-10 microM) or the
      D1 receptor agonist, SKF38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3
      benzazepine; 5 microM), inhibited spike discharge to longer interstimulus
      intervals (40-500 ms) for approximately 10% of striatal cells recorded. The
      inhibition to longer interstimulus intervals was blocked by the D1 receptor
      antagonist, SCH23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3
      benzazepin+ ++-7-ol], but not the D2 antagonist, sulpiride.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1351272
TI  - Effects of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-induced
      hemiparkinsonism on the kinematics of a two-dimensional,multijoint arm movement
      in the rhesus monkey.
AB  - The effects of the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6
      tetrahydropyridine (MPTP) on the kinematics of two-dimensional arm movements in
      the primate were studied. Two rhesus monkeys were trained to move a manipulandum
      at various distances and directions in horizontal space from a centrally located
      target box. Several kinematic parameters including reaction time, and time and
      amplitude of peak tangential velocity were analysed. Following an extensive
      control evaluation period, the animals were unilaterally injected with MPTP into
      the internal carotid artery. The animals were restudied for up to 289 days
      following induction of hemiparkinsonism. Larger-amplitude movements (greater than
      3.5 cm) were more severely affected than smaller amplitude movements. Both
      animals exhibited marked changes in the arm movements including increased time-to
      peak velocity and decreased peak velocity. The degree of the kinematic changes
      was spatially dependent, with the decrease in velocity as well as the time-to
      peak velocity being more pronounced for the larger, outward movements. Reaction
      time increased but showed no spatial dependency. Kinematic deficits persisted
      over the entire time-period studied. Also, the kinematic changes were reduced by
      levo-3,4 dihydroxyphenylalanine in a dose-dependent manner. Tyrosine hydroxylase
      immunohistochemistry documented extensive cell loss in the substantia nigra.
      These results show that both the timing as well as the amplitude of the velocity
      profiles are disrupted by MPTP consistent with the known akinesia and
      bradykinesia of parkinsonism. Although abnormalities were present for all
      directions and distances, a spatial dependency to the deficits was detected. The
      observation of more pronounced changes for larger, outward movements suggests a
      role for the basal ganglia in production of larger-amplitude movements directed
      away from the body.

PMID- 1351273
TI  - Partial dopamine agonist therapy of levodopa-induced dyskinesias.
AB  - We administered the partial dopamine agonist terguride under controlled
      conditions to patients with Parkinson's disease (PD), both as monotherapy and in
      conjunction with intravenous levodopa. Terguride produced a dose-dependent
      decrease in levodopa-induced dyskinesias (up to 53%) in seven patients without
      concomitant worsening of parkinsonism, and had no significant antiparkinsonian
      effect when administered alone. Partial dopamine agonists may hold some promise
      in the adjuvant therapy of patients with advanced PD.

PMID- 1351274
TI  - Transmission of spongiform encephalopathy from a familial Creutzfeldt-Jakob
      disease patient of Jewish Libyan origin carrying the PRNP codon 200 mutation.

PMID- 1351275
TI  - [International College of Surgeons Biannual Congress of the Italian Section - IV.
      In honor of Professor Attilio Basile. Messina, Taormina, 7-9 December 1990].

PMID- 1351276
TI  - [Somatostatin in duodenocephalopancreatectomy for neoplastic pathology].

PMID- 1351277
TI  - [Theoretical and physiopharmacological bases of the somatostatin treatment in
      digestive diseases].

PMID- 1351278
TI  - [A clinical study on the use of somatostatin in the treatment of digestive
      hemorrhage caused by stress ulcer].

PMID- 1351279
TI  - [Use of octreotide in the treatment of pancreatic fistula].

PMID- 1351280
TI  - Abstracts of the 8th International Symposium on Radionuclides in Nephrourology.
      Chester, 6-8 May 1992.

PMID- 1351281
TI  - Prolonged beta-agonist infusion does not induce desensitization or down
      regulation of beta-adrenergic receptors in newborn sheep.
AB  - In adult animals, prolonged beta-agonist exposure leads to down-regulation of
      beta-adrenergic receptors and desensitization. Prior evidence from our lab
      suggests that this may not occur in developing animals. To study this, we
      measured the response to graded epinephrine infusion [2.7, 5.5, 13.6, 27.3
      mumol/(kg.min), (0.5, 1.0, 2.5, 5.0 micrograms/(kg.min)], myocardial beta-agonist
      receptor density, and components of the receptor-cyclase system in newborn lambs
      before (n = 6) and after (n = 5) 3 d of continuous isoproterenol administration
      (2 micrograms/kg/min). beta-Adrenergic receptors were measured by radioligand
      binding. Epinephrine dose-response curves were analyzed for the threshold and
      slope for changes in mean blood pressure, systolic blood pressure, and heart rate
      versus plasma epinephrine levels. Despite 3 d of continuous isoproterenol
      infusion, we observed no desensitization of the hemodynamic response to
      epinephrine. There was a reduction in receptor density when expressed per
      membrane protein [155.3 +/- 19.5 (controls) versus 73.2 +/- 3.8 fmol/mg protein
      (agonist exposed), p less than 0.05], but no alteration in receptor density when
      expressed per g cardiac wet weight [258.8 +/- 39.9 (controls) versus 406.8 +/-
      74.0 fmol/g wet weight (agonist exposed)]. There was no alteration in agonist
      affinity or in adenylyl cyclase activity after adjustment for membrane protein
      recovery. Prolonged beta-agonist infusion in newborn lambs does not desensitize
      hemodynamic responses to infused epinephrine. We propose that receptor regulation
      in developing animals is fundamentally different than in adult animals.

PMID- 1351282
TI  - [Beta blockers today].
AB  - Although beta-blockers have held their own as the cornerstones of cardiological
      treatment for almost twenty years, the beneficial effects of these classic agents
      are not always appreciated in clinical work. Simplified hypertensive treatment or
      other factors may sometimes argue for the use of newer medicines, but many
      pathophysiological manifestations of high blood pressure are still best
      controlled with beta-blockers. The range of available preparations has increased
      and new compounds are continually appearing on the market.

PMID- 1351283
TI  - Portuguese man-of-war envenomation.
AB  - Portuguese man-of-war and jellyfish stings are common occurrence in the coastal
      waters of the southern United States. Signs and symptoms of Portuguese man-of-war
      envenomation usually appear immediately following a sting but may be delayed for
      several hours. Reactions are commonly localized and comprise pain, paresthesia,
      and intense burning with a linear, red, papular eruption or urticaria at the
      contact site. Systemic signs may include nausea, myalgia, headache, chills, or
      pallor. Cardiovascular collapse and death have been reported. Venom can be
      inactivated with dilute acetic acid (vinegar), proteolytic meat tenderizer, or
      baking soda. Tentacle debris should be removed. Resolution of symptoms usually
      occurs within 72 hours, without sequelae.

PMID- 1351284
TI  - HIV encephalopathy and dementia.
AB  - As of July 1991, 10 years after the onset of this modern pandemia, it is
      estimated that greater than 1 million persons worldwide have AIDS, 10 million
      people are HIV infected and by the end of the millenium, there will be 40 to 50
      million persons infected. In the United States, 120,000 persons already have died
      of AIDS and 200,000 currently are infected. It has been calculated that by the
      year 2000, primary CNS lymphoma will be more common than meningiomas. Clearly,
      AIDS-related complications involving the CNS and manifested by behavioral and
      neurologic manifestations will remain one of the most common problems for
      physicians worldwide for years to come.

PMID- 1351286
TI  - 6th International Congress of Pediatric Dermatology. Toronto, Ontario, Canada,
      June 8-11, 1992. Abstracts.

PMID- 1351285
TI  - Neurologic complications of drugs. Tardive dyskinesias, neuroleptic malignant
      syndrome, and cocaine-related syndromes.
AB  - Drugs, either self-administered or prescribed by physicians, can result in
      substantial neurologic disability in psychiatric patients. It is clear that the
      use of neuroleptic agents to treat psychiatric illness may result in a variety of
      tardive movement disorders. Most commonly, these take the form of orobuccal
      dyskinesias, but choreic movements of the trunk and extremities, dystonic
      postures, myoclonus, tics, parkinsonism, and akathisic syndromes also may occur.
      The choreic tardive syndromes are thought to occur more commonly in the elderly
      female population, but tardive variants may affect a different population. The
      neuroleptic malignant syndrome carries a significant mortality and remains a
      diagnostic and therapeutic challenge. Early detection and vigorous treatment
      reduces the morbidity and mortality from this condition. Stroke, seizures, and
      various movement disorders may complicate the illicit use of cocaine and
      complicate the rehabilitation of those patients dependent on its use. The
      unsatisfactory treatment of tardive syndromes, neuroleptic malignant syndrome,
      and cocaine-induced neurologic disease underscores our incomplete understanding
      of the neurochemistry of dopamine, the function of newly discovered dopamine
      receptors, and the role they play in maintaining normal emotional and motoric
      function. For now, awareness of the varied neurologic syndromes related to
      neurotransmitter-modulating agents should provide the impetus for careful use of
      these agents and for the continued development of improved drugs for the
      treatment of psychiatric disease.

PMID- 1351287
TI  - Congestive heart failure with normal ejection fraction. A different mechanism
      requiring different therapy.
AB  - Clinicians must remain undaunted when history, physical examination, and chest
      radiography suggest congestive heart failure but left ventricular systolic
      function is normal. Many of these patients have diastolic dysfunction, and
      standard therapy for left ventricular systolic dysfunction is often ineffectual
      or detrimental. Noninvasive testing is subject to many pitfalls but may confirm a
      clinical suspicion and provide indications to treat or to proceed with invasive
      testing. In the absence of clinical signs and symptoms of congestive failure,
      however, abnormal diastolic indexes should not be interpreted as diagnostic of
      diastolic dysfunction and are not an indication to treat.

PMID- 1351288
TI  - Cytoprotective effect of reduced glutathione in hydrogen peroxide-induced
      endothelial cell injury.
AB  - The kinetic effects of hydrogen peroxide (H2O2) on cultured endothelial cells
      isolated from bovine carotid artery were studied. The cytoprotective effects of
      glutathione (GSH) on H2O2-induced cell injury were also investigated. H2O2
      induced a dose- and time-dependent cell injury in cultured endothelial cells.
      H2O2-induced cell injury was blocked by simultaneous treatment by catalase, but
      not by superoxide dismutase. H2O2 also induced endogenous PGI2 biosynthesis, and
      the maximum PGI2 production was reached after 1 h treatment. Stimulation of PGI2
      production was parallel with arachidonate release from H2O2-treated cells.
      However the prostaglandin biosynthesis enzyme activity in cells was inhibited by
      H2O2 treatment. When the cells were treated with GSH, the intracellular GSH
      reached a plateau after 3 h treatment. Both H2O2-induced cell injury and PGI2
      production were significantly inhibited by the 3 h pretreatment with GSH. The
      cytoprotective effect of GSH was completely inhibited by buthionine sulfoximine
      which is a specific inhibitor of gamma-glutamylcysteine synthetase. The results
      indicate that the cytoprotective effect of GSH on H2O2-induced cell injury in
      cultured bovine carotid artery endothelial cells depends on the increase in
      intracellular GSH content.

PMID- 1351289
TI  - Conformational coupling in DNA polymerase information transfer.
AB  - The extraordinary fidelity of DNA replication during forward polymerization and
      exonuclease error correction is largely a function of a conformational change
      that occurs in response to a correct dNTP binding to properly base-paired duplex
      DNA. The conformational change serves as a kinetic barrier to effect the rapid
      incorporation of correct bases while minimizing the rate of polymerization with
      incorrect bases and allowing for selective removal of mismatches. However, in
      spite of the number of attractive features to the conformational change model,
      the evidence in support of such a rate-limiting step is still subject to
      significant uncertainty. It is the challenge of further work on DNA polymerases
      as well as many other enzyme systems to devise new methods to define the
      transient state of the enzyme during catalysis and to relate the kinetic and
      thermodynamic parameters to the enzyme structure.

PMID- 1351290
TI  - Kinesin and myosin ATPases: variations on a theme.
AB  - The enzymes kinesin and myosin are examples of molecular motors which couple ATP
      hydrolysis to directed movement of biological structures. Myosin has been
      extensively studied and its structure and mechanism of coupling are known in
      detail. Much less is known about kinesin, but many of its major properties are
      similar to those of myosin. Both enzymes have two catalytic head groups at the
      end of a long alpha-helical rod. The head groups contain the sites for ATP
      hydrolysis and interaction with their respective partners for movement
      (microtubules or F-actin). In each case the binding and hydrolysis of ATP is
      rapid and the steady state ATPase rate is limited by a slow step in the region of
      product release. This slow release of product is accelerated by interaction with
      actin or microtubules coupled to changes in binding affinity. As there is no
      evidence for a close evolutionary link between kinesin and myosin, these and
      other similarities may represent convergence to set of common functional
      properties which are constrained by the requirements of protein structure and the
      use of ATP hydrolysis as a source of energy. It will be of particular interest to
      determine if these common properties are also shared by the large number of
      divergent proteins which have recently been discovered to possess a domain which
      is homologous to the head group of kinesin.

PMID- 1351291
TI  - The role of nucleoside triphosphate hydrolysis in transducing systems: p21ras and
      muscle.
AB  - A variety of systems use nucleoside triphosphate hydrolysis to control or provide
      energy for biological processes, mediated through protein-protein interactions.
      The nature of this coupling may vary, but often there is a degree of similarity.
      In this paper, two systems are compared: actomyosin in muscle and p21ras in a
      signal transduction pathway as yet undefined. The mechanism of the nucleotide
      triphosphate hydrolysis and the consequent changes in the protein-nucleotide
      complex have been investigated, to understand how the coupling to biological
      function is achieved. The basal nucleoside triphosphatase mechanisms are compared
      and the roles of proteins that activate the hydrolysis, actin and GAP, are
      discussed. The cleavage process was probed by stereochemical techniques to
      determine the basic mechanism, of either a phosphorylated enzyme intermediate or
      direct displacement of nucleoside diphosphate by water. Phosphate-water oxygen
      exchange probes were used to investigate nucleoside triphosphate and inorganic
      phosphate release steps. A new method of probing the kinetics of inorganic
      phosphate release directly has been developed. In muscle, this process seems
      likely to be related directly to force generation. In the GAP-ras system,
      measurement of phosphate release is allowing the mechanism of the GAP-p21ras
      interaction to be probed.

PMID- 1351292
TI  - Nucleotides and divalent cations as effectors and modulators of exocytosis in
      permeabilized rat mast cells.
AB  - The idea that the universal trigger to exocytosis (the terminal step in the
      secretory process) is an elevation of the cytosol concentration of Ca2+, and that
      it is dependent on ATP, is no longer tenable. Working with streptolysin-O
      permeabilized mast cells (and other myeloid cells) we have shown that non
      hydrolysable analogues of GTP can stimulate exocytosis after depletion of Ca2+
      (i.e. at concentrations below 10(-9) M) and ATP. Such Ca2+- and ATP-independent
      exocytosis is strongly dependent on the presence of Mg2+, and the requirement for
      Mg2+ declines as the concentration of Ca2+ is brought up to 10(-7) M. We argue
      that Ca2+ serves to regulate the binding of guanine nucleotides to GE, a GTP
      binding protein that regulates exocytosis through its interaction with CE, a
      calcium-binding protein which serves as an intracellular pseudo-receptor. The
      onset of exocytosis, following provision of Ca2+ and guanine nucleotides to the
      permeabilized cells, is preceded by delays which are sensitive to the order of
      provision of the two effectors (i.e. Ca2+ and guanine nucleotides), the presence
      or absence of Mg2+, and the identity of the activating guanine nucleotide. In
      view of the similarity of these features with the activation kinetics of adenylyl
      cyclase, we argue that GE behaves as a member of the heterotrimeric class of
      signal transducing G-proteins such as GS.

PMID- 1351293
TI  - Studies on the structure and mechanism of H-ras p21.
AB  - Current knowledge of the structure of H-ras p21 is reviewed with particular
      emphasis on the interaction between guanine nucleotides and the active site of
      the protein. The nature of the conformational change induced by GTP hydrolysis is
      discussed. The major change is seen in the region known as the effector loop
      (loop 2), with significant but less well-defined changes occurring in loop 4,
      which is implicated in the GTPase reaction. Other evidence concerning the
      mechanism of GTP hydrolysis and its activation by GAP (GTPase-activating protein)
      is also discussed. Evidence regarding the rate limiting step in the p21 GTPase
      reaction, and the manner in which this and possibly other steps are accelerated
      by GAP, is inconclusive.

PMID- 1351294
TI  - Hormone signalling via G-protein: regulation of phosphatidylinositol 4,5
      bisphosphate hydrolysis by Gq.
AB  - Heterotrimeric GTP-dependent regulatory proteins (G-proteins) mediate modulation
      by many cell surface receptors. Activation of the G-proteins promotes
      dissociation of their alpha and beta gamma subunits. The similarity of behaviour
      of beta gamma subunits derived from a variety of G-proteins has led to their use
      as affinity reagents for the analysis of the more unique alpha subunits. The
      evolution of these uses is presented. One of the more insightful results was the
      isolation of a new class of G-protein alpha subunits (the alpha q subfamily)
      which have been shown to regulate the activity of a phospholipase C (PLC)
      specific for phosphatidylinositols. The experimental evidence leading to this
      conclusion is discussed. The activation by alpha q increases the apparent Vmax of
      the beta isoform of phosphatidylinositol-specific phospholipase C (PLC beta) and
      can be modulated by beta gamma subunits.

PMID- 1351295
TI  - Coupling of ras p21 signalling and GTP hydrolysis by GTPase activating proteins.
AB  - Ras p21 proteins cycle between inactive, GDP-bound forms and active GTP-bound
      forms. Hydrolysis of bound GTP to GDP is mediated by proteins referred to as
      GAPs, two forms of which have been described. The first, p120-GAP, contains
      regions of homologies with tyrosine kinase oncogenes, and interacts with tyrosine
      phosphoproteins as well as with ras proteins; p120-GAP may therefore connect
      signalling pathways that involve tyrosine kinase and ras p21 proteins. The second
      type of GAP is the product of the neurofibromatosis type 1 gene (NF1-GAP). This
      is a protein of 325,000 Da that is defective in patients with NF1; NF1-GAP is
      regulated by signalling lipids, and may serve to connect ras p21 with
      phospholipid second messenger systems. The significance of ras p21 interaction
      with distinct GAPs is discussed.

PMID- 1351296
TI  - The kinetic mechanism of the GAP-activated GTPase of p21 ras.
AB  - Guanine nucleotides modified by acetylation of the ribose moiety with the small
      fluorophore N-methylanthranilic acid(mant) have been shown to bind to p21 ras
      with similar equilibrium and kinetic rate constants as the parent nucleotides.
      Hydrolysis of p21.mantGTP to p21.mantGDP results in a 10% decrease in
      fluorescence intensity occurring at the same rate as the cleavage step. A similar
      process occurs with the non-hydrolysable analogue mantGMP.PNP, and this has led
      to the proposal that a conformational change of p21.mantGTP precedes and controls
      the rate of the cleavage step. The fluorescence change with p21.mantGMP.PNP is
      accelerated in the presence of the C-terminal catalytic domain of GAP, which is
      consistent with this mechanism. The same conformational change does not occur
      with oncogenic mutants of p21 ras, Asp-12 and Val-12, but does occur with the
      weakly oncogenic Pro-12 mutant. Stopped flow measurements of the interaction of
      GAP with p21.mantGTP show an exponential decrease in fluorescence, the rate of
      which does not vary linearly with GAP concentration. These data imply a rapidly
      reversible formation of the p21.mantGTP complex with GAP followed by the
      isomerization of this complex. This is at least 10(5)-fold faster than the same
      process in the absence of GAP.

PMID- 1351297
TI  - Photochemical mapping of the active site of myosin.
AB  - The active sites of myosin from skeletal, smooth and scallop muscle have been
      partly characterized by use of a series of photoreactive analogues of ATP.
      Specific labelling was attained by trapping these analogues in their diphosphate
      forms at the active sites by either cross-linking two reactive thiols (skeletal
      myosin) or by formation of stable vanadate-metal ion transition state-like
      complexes (smooth muscle and scallop myosin). By use of this approach combined
      with appropriate chemistry, several key residues in all three myosins have been
      identified which bind at or near the adenine ring, the ribose ring and to the
      gamma-phosphate of ATP. This information should aid in the solution of the
      crystal structure of the heads of myosin and in defining a detailed structure of
      the ATP binding site.

PMID- 1351298
TI  - The actomyosin ATPase: a two-state system.
AB  - Studies of the interaction between actin and myosin subfragment 1 (S1) in
      solution have shown that the association reaction takes place in at least two
      steps. Initially the association is relatively weak to form a complex called the
      A state which can then isomerize to the R state. The rate and equilibrium
      constants for the isomerization have been measured and are shown to depend upon
      the nucleotide bound to the S1 ATPase site; with ATP bound the A state is
      preferred but as ATP is hydrolysed and the products are sequentially released
      then the complex gradually shifts to the A state. An extensive series of
      experiments have characterized the A-to-R isomerization both in solution and in
      contracting muscle fibres and have shown it to be closely associated with the key
      events in the ATP-driven contraction cycle: the conformational change from the A
      to the R state can be monitored by fluorescent probes on either actin or the
      nucleotide; the isomerization can be perturbed by increases in hydrostatic
      pressure; the actin-induced acceleration of the rate of product release from
      myosin is coupled to the A-to-R isomerization; tropomyosin may control actin and
      myosin interaction by controlling the isomerization step and finally pressure
      perturbations of contracting muscle fibres shows there to be a close coupling
      between the isomerization of acto.S1 and the force generating event of muscle
      contraction.

PMID- 1351299
TI  - Nitrogenase of Klebsiella pneumoniae: an MgATP hydrolysing energy transduction
      system with similarities to actomyosin and p21 ras.
AB  - The mechanism of ATP hydrolysis by nitrogenase shows some similarity to that
      proposed for actomyosin and for GTP hydrolysis by p21 ras. All three systems
      involve the formation of an active complex from two component proteins,
      nucleotide-induced changes in protein conformation, energy transduction that in
      the case of nitrogenase involves a decrease in redox potential of metal centres,
      and a slow dissociation of the protein complex. Metal ion activation (Mg2+ or
      Ca2+) and in-line displacement of ADP by H2O without enzyme phosphorylation are
      also common features. At 5 degrees C, stopped-flow calorimetry shows that the
      kinetic and thermodynamic parameters for endothermic, reversible on-enzyme
      cleavage of MgATP by nitrogenase and myosin subfragment 1 are remarkably similar.
      [18O4]Pi-water exchange studies also show that ATP cleavage on nitrogenase and
      myosin are reversible.

PMID- 1351300
TI  - DNA supercoiling and relaxation by ATP-dependent DNA topoisomerases.
AB  - Bacterial DNA gyrase and the eukaryotic type II DNA topoisomerases are ATPases
      that catalyse the introduction or removal of DNA supercoils and the formation and
      resolution of DNA knots and catenanes. Gyrase is unique in using ATP to drive the
      energetically unfavourable negative supercoiling of DNA, an example of
      mechanochemical coupling: in contrast, eukaryotic topoisomerase II relaxes DNA in
      an ATP-requiring reaction. In each case, the enzyme-DNA complex acts as a 'gate'
      mediating the passage of a DNA segment through a transient enzyme-bridged double
      strand DNA break. We are using a variety of genetic and enzymic approaches to
      probe the nature of these complexes and their mechanism of action. Recent studies
      will be described focusing on the role of DNA wrapping on the A2B2 gyrase
      complex, subunit activities uncovered by using ATP analogues and the coumarin and
      quinolone inhibitors, and the identification and functions of discrete subunit
      domains. Homology between gyrase subunits and the A2 homodimer of eukaryotic topo
      II suggests functional conservation between these proteins. The role of ATP
      hydrolysis by these topoisomerases will be discussed in regard to other energy
      coupling systems.

PMID- 1351301
TI  - Nucleotide hydrolysis regulates the dynamics of actin filaments and microtubules.
AB  - Actin filaments and microtubules are major dynamic components of the cytoskeleton
      of eukaryotic cells. Assembly of these polymers from monomeric actin or tubulin
      occurs with expenditure of energy, because ATP (or GTP) tightly bound to actin
      (or tubulin) is irreversibly hydrolysed during polymerization. Therefore, actin
      filaments an microtubules are dissipative structures. Our purpose has been to
      understand how the dissipation of chemical energy perturbs the laws of reversible
      helical polymerization defined by Oosawa, and affects the dynamics of these
      polymers. A kinetic study has shown that nucleotide is hydrolysed on the polymer
      within at least two steps consecutive to the incorporation of the monomer:
      cleavage of the gamma-phosphoester bond followed by the slower release of Pi;
      only the second reaction appears reversible. Pi release, and not cleavage of the
      gamma-phosphate, is linked to the destabilization of protein-protein interactions
      in the polymer, and therefore plays the role of a conformational switch. The
      dynamic properties of the polymer in the NTP- and NDP-Pi intermediate states of
      the assembly process have been investigated using non-hydrolysable analogues of
      nucleotides and structural analogues of Pi, AlF4- and (BeF3-, H2O). Because
      nucleotide hydrolysis is uncoupled from polymerization, actin filaments and
      microtubules grow with a 'cap' of terminal NTP- and NDP-Pi-subunits that interact
      strongly, and prevent the rapid depolymerization of the unstable core of the
      polymer formed of NDP-subunits. The fact that the dynamic properties of the
      polymer are affected by bound nucleotide results in a nonlinear dependence of the
      rate of elongation on monomer concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351302
TI  - Self-organization of polymer-motor systems in the cytoskeleton.
AB  - Microtubules and actin filaments are organized into dynamic arrays inside cells.
      In this paper I discuss in conceptual form the assembly mechanisms of three
      specific arrays: asters, spindles and leading edge structures. The role of energy
      transducing processes, particularly motor protein activity, in assembly is
      explored. I conclude that dynamic interaction between motor proteins and
      cytoskeletal polymers play a very general role in spatial organization of the
      cytoplasm.

PMID- 1351303
TI  - Flesinoxan shows antidepressant activity in a DRL 72-s screen.
AB  - Schedules which selectively reinforce low rates of responding (DRL, differential
      reinforcement of low rate) distinguish between antidepressants and other types of
      drugs. In a DRL schedule a subject is required to pause for a specified minimum
      period of time between two consecutive responses in order to obtain a reinforcer.
      The dependent variables are rate of responding and rate of reinforcement.
      Response patterns of rats treated with clinically effective antidepressant drugs
      such as imipramine (2.0-32.0 mg/kg) or fluvoxamine (4.0-32.0 mg/kg) are
      characterized by a decrease in response rate and an increase in reinforcement
      rate. Treatment with the 5-HT1A agonist flesinoxan (0.1-3.0 mg/kg) also dose
      dependently decreased response rates while at the same time increasing
      reinforcement rates. Chlordiazepoxide (2.5-20.0 mg/kg) and diazepam (0.25-2.0
      mg/kg) had no effects in the present experiment. d-Amphetamine increased response
      rates at low doses (0.5-2.0 mg/kg), and decreased it at the higher doses (4.0
      mg/kg), but reinforcement rates were unaltered. Overall analysis of the effects
      of haloperidol (0.02-0.32 mg/kg) showed decreased responding and increased
      reinforcement rates. Post hoc analysis, however, clearly differentiated between
      haloperidol's profile and that of the antidepressants. As such, the results of
      the present experiment show that flesinoxan might possess antidepressant activity
      in humans.

PMID- 1351304
TI  - A comparison of various antidepressant drugs demonstrates rapid desensitisation
      of alpha 2-adrenoceptors exclusively by sibutramine hydrochloride.
AB  - The functional status of presynaptic and postsynaptic alpha 2-adrenoceptors in
      murine brain was respectively monitored using the hypoactivity (sedation) and
      mydriasis (pupil dilatation) responses to clonidine (0.1 mg/kg IP). Both
      responses were attenuated 24 h after 3 days of injection of sibutramine
      hydrochloride (3 mg/kg IP). To ascertain whether this property was exclusive to
      sibutramine, the following antidepressant drugs were also tested for their
      ability to down-regulate alpha 2-adrenoceptors rapidly: amitriptyline, doxepin,
      nomifensine, desipramine, amoxapine, fluoxetine, zimeldine, tranylcypromine and
      mianserin. When given for 3 or 5 days at the low dose of 3 mg/kg IP, none of the
      other antidepressants reduced clonidine-induced hypoactivity or mydriasis.
      Furthermore, increasing the dose of amitriptyline, doxepin, nomifensine,
      desipramine, amoxapine and tranylcypromine to 10 mg/kg IP did not enable these
      antidepressants to attenuate the alpha 2-adrenoceptor-mediated responses after 3
      days of treatment. An electroconvulsive shock (ECS; 200 V, 2 s) given once daily
      attenuated clonidine-induced mydriasis, but not hypoactivity, when administered
      for 3 days and both responses when administered for 5 days. In conclusion, this
      comparative study using antidepressant treatments with differing pharmacological
      modes of action demonstrated that sibutramine was the only drug which rapidly
      down-regulated pre- and postsynaptic alpha 2-adrenoceptors. ECS down-regulated
      postsynaptic alpha 2-adrenoceptors when given for 3 days, but required 5 days to
      desensitise both alpha 2-adrenoceptor populations.

PMID- 1351305
TI  - Measurement of depression and negative symptoms in schizophrenia.
AB  - The validity of the Hamilton Depression Scale (HAM-D) as a measure of depressive
      symptomatology in schizophrenic patients is questionable since it was not
      developed for this purpose, nor has it been validated in a schizophrenic
      population. Accordingly, 80 schizophrenic inpatients were administered the HAM-D,
      the 18-item Brief Psychiatric Rating Scale (BPRS), and the Scale for the
      Assessment of Negative Symptoms (SANS) at drug-free baseline and after 4 weeks of
      neuroleptic treatment. The findings revealed that the HAM-D total score was
      nonspecific, while individual HAM-D subfactors provided a better index of various
      symptom complexes. The HAM-D contained a depressive factor that correlated
      strongly with the BPRS depression factor and a negative symptom factor that
      correlated strongly with the SANS and the BPRS negative symptom factor. These
      findings suggest the need to utilize specific assessment techniques rather than
      global measures when assessing depression in schizophrenia.

PMID- 1351306
TI  - [Molecular biology of positional information and positional value in
      morphogenesis].

PMID- 1351307
TI  - [Familial pheochromocytoma in Sipple's syndrome. A comparison between
      scintigraphy with 131I-meta-iodobenzylguanidine, computed tomography and
      echography].

PMID- 1351309
TI  - [New positive inotropic drugs in acute and chronic heart failure].
AB  - Beta-adrenergic stimulants (Dobutamine and Dopamine) and recently introduced
      phosphodiesterase inhibitors (PDI) such as Amrinone, Milrinone, Enoximone and
      Piroximone are the principal inotropic agents for the treatment of acute cardiac
      failure. Most of the hemodynamic effects of these drugs are comparable, but
      peripheral vasodilatation is more marked with PDI. A potential advantage of the
      latter group is the lack of development tolerance, which occurs within 48 to 72
      hours after beta-stimulants. On simultaneous administration, additive effects can
      be observed. Short term clinical results with PDI are good, especially in
      patients with postoperative cardiocirculatory failure, including cardiogenic
      shock. In contrast, long-term oral treatment with Amrinone, Milrinone and
      Enoximone in recent studies was disappointing. Efficacy was not superior to
      Digoxin, and unwanted side effects were frequent. Intermittent instead of
      continuous administration of positive inotropic agents should be evaluated in
      patients with severe congestive heart failure not responding to vasodilators and
      diuretics.

PMID- 1351308
TI  - Estimation of time since exposure for a prevalent cohort.
AB  - In natural history studies of human immunodeficiency virus type 1 (HIV-1)
      infection a substantial proportion of participants are seropositive at time of
      enrollment in the study. These participants form a prevalent subcohort.
      Estimation of the unknown times since exposure to HIV-1 in the prevalent
      subcohort is of primary importance for estimation of the incubation time of AIDS.
      The subset of the cohort that tested negative for antibody to HIV-1 at study
      entry and was observed to seroconvert forms the incident subcohort that provides
      longitudinal data on markers of maturity (that is, duration) of infection. We use
      parametric life table regression models incorporating truncation to describe the
      conditional distribution (imputing model) of the times since seroconversion given
      a vector of the markers of maturity. Using the fitted model and the values of the
      markers of maturity of infection provided by the seroprevalent subcohort at entry
      into the study, we can impute the unknown times since seroconversion for the
      prevalent subcohort. We implement multiple imputation based on a model-robust
      estimate of the covariance matrix of parameters of the imputing model to provide
      confidence intervals for the geometric mean of the time since seroconversion in
      the prevalent subcohort, and to compare maturity of infection of cohorts
      recruited in different cities. The accuracy of imputation is further validated by
      comparisons of imputation-based estimates of AIDS incubation distribution in the
      seroprevalent subcohort with more direct estimates obtained from the seroincident
      subcohort.

PMID- 1351310
TI  - [Primary prevention of varicose bleeding: current status].
AB  - 1. Surgical shunts should be abandoned for prevention of the first bleeding
      because of an increased mortality rate, despite a marked reduction in frequency
      of bleeding. 2. Sclerotherapy is not recommended for clinical practice in
      preventing the first bleeding. The meta-analysis of numerous randomized clinical
      trials shows a small effect on bleeding risk and mortality rate. But these
      effects are remarkably heterogenous in various studies and are compensated by the
      complications of sclerotherapy. 3. Prophylactic treatment with beta-blockers has
      similar results as sclerotherapy documented by meta-analysis of several studies.
      In contrast to sclerotherapy both risk and side effects are minimal. More
      controlled clinical trials are needed to define subgroups of patients with higher
      benefit of the prophylaxis. In individual high-risk patients (size of varices,
      liver dysfunction, red-colour-signs) beta-blocker prophylaxis may have possible
      benefit.

PMID- 1351311
TI  - [Current aspects in the diagnosis of fragile X syndrome].

PMID- 1351312
TI  - [Axonal neuropathy and salazosulfapyridine: slow-acetylator phenotype].
AB  - We report a case of an axonal sensorimotor neuropathy involving
      salazosulphapyridine in a slow-acetylator patient with ulcerative colitis. Rather
      than hypersensitivity the mechanism of the neuropathy can be assumed to be
      toxicity. The role played by the respective different metabolites in the
      occurrence of this uncommon side effect is uncertain.

PMID- 1351313
TI  - [Treatment understanding and compliance in asthma of children. Results of a
      prospective survey].
AB  - Compliance with treatment is a crucial factor in the management of asthmatic
      children which depends on the understanding of the disease and its treatment. The
      understanding of, and compliance with treatment were evaluated by means of a
      questionnaire in 50 parents of asthmatic children. 50% of these parents used anti
      histamines as maintenance treatment and 30% also used these drugs during attacks.
      Half the parents knew about the bronchodilator effects of theophylline and B2
      agonists. 42% and 30% respectively of the parents thought that the side-effects
      of theophylline or corticosteroids were few or inexistent; 86% claimed regular
      attendance to out-patient clinics, but 30% confessed that they had forgotten such
      drugs as theophylline and antihistamines. 50% took the appropriate therapeutic
      measures when confronted with a moderate or severe attack of asthma. Each child
      received 2.3 drugs on average for his or her asthma. This study shows that
      parents have an insufficient knowledge of asthma treatments, and this may
      partially explain the poor compliance with therapy as well as the morbidity and
      mortality associated with childhood asthma.

PMID- 1351314
TI  - [Medullary cancer of the thyroid and multiple endocrine neoplastic syndromes].
AB  - Despite its rarity, medullary thyroid carcinoma which is hereditary in a quarter
      of cases and often associated with multiple endocrine neoplasia 2a and 2b
      syndromes, avises much interest which has lead to the formation of a French
      multidisciplinary group for the study of calcitonin tumors. This collaboration
      has resulted in the establishment of a national register and has broadened the
      knowledge of all specialists concerned. Consequently diagnostic methods are
      improved, becoming quicker, more reliable and also more thorough due to the
      setting up of therapeutic protocols. An immunocytochemical staining for
      calcitonin allows a preoperative diagnosis, providing optimal therapeutic
      conditions for the patients, especially systematic research of pheochromocytoma
      and management by a specialized team. Total thyroidectomy and careful lymph node
      dissection are recommended for all cases. Such progress significantly modifies
      the prognosis of the disease. Family screening, using plasma calcitonin and, in
      the near future, genetic studies will hopefully enable the identification of
      abnormal gene carriers before the clinical stage, thus making total recovery
      possible.

PMID- 1351315
TI  - MHC class II beta-chain expression in the rainbow trout.
AB  - A cDNA clone corresponding to the MHC class II beta-chain of the rainbow trout
      (Oncorhynchus mykiss) has been isolated and used in restriction fragment length
      polymorphism (RFLP) studies in a family of full siblings of rainbow trout. A very
      simple RFLP pattern was detected, suggesting segregation of a homozygote AA
      genotype and a heterozygote AB genotype. The MHC class II beta-chain of the
      rainbow trout seems to be transcribed in the same type of cells as class II genes
      of higher vertebrates even though the cDNA clone recognizes atypical messenger
      sizes of 2.2 kb and 3.6 kb in the analysed family. Surprisingly the transcripts
      seem to be allele-specific for the assigned genotypes.

PMID- 1351317
TI  - Takayasu's arteritis syndrome associated with systemic lupus erythematosus.
AB  - Takayasu's arteritis (TA) rarely coexists with systemic lupus erythematosus
      (SLE). Eighteen cases of TA associated with SLE found by worldwide literature
      search are reviewed, and an additional unique case is reported in association
      with the presence of anti-cardiolipin antibody. Patients with TA and/or SLE have
      similar age of onset and female predominance. The absence of specific SLE markers
      in patients with TA who subsequently develop SLE suggests that the coexistence of
      these conditions may be coincidental. The antiphospholipid syndrome in patients
      with SLE may mimic the occlusive vasculitis of TA.

PMID- 1351316
TI  - Scoring a technical knockout in mice.

PMID- 1351319
TI  - Takayasu's arteritis.

PMID- 1351318
TI  - Tyrosine kinase signal transduction in rheumatoid synovitis.
AB  - Explants of synovial cells in rheumatoid arthritis display a transformed
      phenotype with focus formation and anchorage-independent growth. Many of the
      cytokines that activate these fibroblasts mediate their action through tyrosine
      kinase growth factor receptors. Mechanisms of signal transduction via such
      tyrosine kinases are therefore relevant to the pathogenesis of rheumatoid
      lesions. Data are presented using the neu oncogene product p185neu as a model
      system to explore signal transduction by receptor tyrosine kinases. Evidence is
      shown that increased tyrosine kinase activity in the oncogenic form of this
      protein may result from dimerization of the tyrosine kinase receptor. In the
      normal cellular counterpart of p185neu, dimerization appears to be mediated by
      the action of an as yet unidentified ligand. Dimerization also appears to be
      important in signal transduction mediated by epidermal growth factor, platelet
      derived growth factor, and colony-stimulating factor 1. These cytokines also
      alter the phenotype of rheumatoid synovial fibroblasts to resemble transformed
      fibroblasts. Additionally, preliminary data that suggest increased tyrosine
      kinase activity in rheumatoid arthritis synovia compared with osteoarthritis
      synovia are presented. Molecular characterization of tyrosine kinase receptors
      will be an important direction for future studies of the pathogenesis of
      rheumatoid disease.

PMID- 1351320
TI  - Pharmacological characterization of excitatory synaptic potentials in rat
      basolateral amygdaloid neurons.
AB  - The pharmacological properties of synaptic responses in rat basolateral
      amygdaloid (BLA) neurons were studied using intracellular recording techniques.
      Three distinct types of synaptic potential were evoked by stimulation of the
      adjacent ventral endopyriform nucleus: 1) a fast excitatory postsynaptic
      potential (f-EPSP); 2) a late EPSP (1-EPSP) following the f-EPSP; and 3) a
      multiphasic hyperpolarization following the initial depolarizing potential.
      Superfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective non-N
      methyl-D-aspartate (non-NMDA) receptor antagonist, blocked the f-EPSP in a
      concentration-dependent manner. The ED50 for this effect was around 4 microM. In
      the presence of CNQX, however, a small depolarizing potential remained. This
      residual depolarizing component was markedly enhanced on removing Mg++ from the
      perfusing medium and could subsequently be abolished by DL-2-amino-5
      phosphonovaleate (DL-APV, 50 microM) indicating its mediation via NMDA receptor
      coupled ionophore. The l-EPSP was reversibly blocked by DL-APV. These results
      suggest that the pyriform cortex-amygdala pathway is mediated through excitatory
      amino acids acting on non-NMDA as well as NMDA receptors located on the BLA
      neurons.

PMID- 1351321
TI  - Neonatal 6-OHDA lesions differentially affect striatal D1 and D2 receptors.
AB  - Lesions to the dopamine (DA) system in early postnatal development have different
      behavioral consequences compared to lesions made in adulthood. Intrastriatal
      injections of the neurotoxin 6-hydroxydopamine (6-OHDA) on the day of birth (PO)
      or postnatal day 1 (P1) produce a selective supersensitivity to D1 receptor
      agonists and a subsensitivity to D1 antagonists (Neal and Joyce, 1991a). In this
      paper, we describe the long-term effects of early DA loss on DA receptor
      regulation. Pups received bilateral intrastriatal injections of the neurotoxin 6
      OHDA (4 micrograms per striatum) on PO or P1. Adult rats were killed at 90 days
      of age and the brains were processed for quantitative autoradiography (QAR) or
      tyrosine hydroxylase (TH) immunocytochemistry. Cohorts were tested for the
      behavioral responses to the selective D1 receptor agonist SKF38393 (10 mg/kg).
      Neonatally lesioned rats exhibited increases in abnormal perioral movements in
      response to D1 receptor stimulation. There was a heterogenous and patchy loss (40
      50%) of [3H]mazindol binding to high-affinity DA uptake sites (a marker of DA
      terminal density) and a similar loss of TH-like immunoreactivity within the
      striata of the neonatally lesioned rats. There was also a reduction in the number
      of mu-opioid receptor patches (labelled with [3H]naloxone), a marker for the
      striatal patch compartment, and a similar patchy loss of D1 binding sites
      (labeled with [3H]SCH23390). The binding of [3H]spiroperidol to D2 sites was not
      altered. This is in contrast to the changes observed following adult 6-OHDA
      lesions, wherein there is a significant increase in the number of D2 binding
      sites (Joyce, 1991a,b). The results are discussed with respect to the behavioral
      consequences of neonatal lesions and the differences between neonatal and adult
      lesions.

PMID- 1351322
TI  - Heart allografts in murine systems. The differential activation of Th2-like
      effector cells in peripheral tolerance.
AB  - Activated CD4+ Th2 cells release cytokines (IL-4,-10) that block activation &
      cytokine (IL-2/IFN-gamma) release by proinflammatory T (CD4+,CD8+) effector
      cells. To test the hypothesis that peripheral tolerance to alloantigen is linked
      to differential activation of CD4+ Th2 cells we measured cytokine transcripts in
      heart grafts (C57BL/10----C3H/HeJ) and spleens of mice rendered "tolerant" by
      donor-specific blood transfusion, anti-CD4 mAb pretreatment, and cyclosporine
      administration. The expression of IL-2/IFN-gamma transcripts was reduced greater
      than 90% in grafts from tolerant recipients. IL-4/IL-10 transcripts were
      generally enhanced and persisted in graft and recipient spleen. Accordingly
      adoptive transfer studies were performed to determine whether Th2-like effectors,
      which express Fc receptors (FcR), mediate suppression in this model.
      Unfractionated mononuclear cells (MC) (5 x 10(6), isolated from spleens of heart
      graft recipients made tolerant by DST, prolonged the survival of test grafts
      greater than 90 days in irradiated (680 rads) recipients reconstituted with a
      sufficient number of MC from spleens of naive C3H to precipitate rejection of the
      test graft in 18.2 days (MST, n = 5). Conversely adoptive transfer of inocula
      depleted of FcR+ cells on immune complex columns or with anti-FcR mAb 24G2 caused
      test grafts to be rejected in 8-11 days. These results suggest that peripheral
      tolerance to alloantigen may be linked to differential activation of Th2 cells
      that induce anergy by suppression. The possibility that Th2-like effectors
      mediate peripheral tolerance to self is discussed.

PMID- 1351323
TI  - Effect of University of Wisconsin solution pancreas preservation period on
      function of isolated human islets.

PMID- 1351325
TI  - Second International Symposium on Small Bowel Transplantation. London, Ontario,
      October 3-5, 1991.

PMID- 1351326
TI  - Proceedings of the IIIrd International Congress on Pancreatic and Islet Cell
      Transplantation and Symposium on Artificial Insulin Delivery Systems. Lyon,
      France.

PMID- 1351324
TI  - Reversal of diabetes by the induction of islet cell neogenesis.

PMID- 1351327
TI  - Local immunity in the mammary gland.
AB  - The mammary glands of pregnant and non-pregnant sheep were stimulated by infusion
      of killed Staphylococcus aureus, and the lymphoid cell response delineated with a
      panel of monoclonal antibodies. Seven days after antigen infusion, the mammary
      glands of both pregnant and non-pregnant sheep displayed a striking feature,
      characterised by the presence of numerous CD45R+ MHC class II+ B cells in the
      periductal connective tissues. These cells were seen to be clustering around
      blood capillaries with very prominent endothelial cell lining. Some CD5+ CD4+
      lymphocytes were scattered among the B-cell clusters, whereas a few CD8+
      lymphocytes were seen mainly at the periphery of the B-cell clusters. Fourteen
      days after antigen infusion, numerous plasma cells were observed, most of them
      being of the IgA isotype. Seven days after parturition (approximately 40 days
      after antigen infusion) the number of lymphocytes and plasma cells in the infused
      glands had declined dramatically. These data indicate that B cell and helper T
      cell interaction can take place at the local sites of antigen stimulation in the
      mammary gland.

PMID- 1351328
TI  - [H2-blocker refractory ulcers: what can be done?].
AB  - H2-receptor antagonist refractory ulcers are seldom. Less than 5% of duodenal
      ulcers do not heal under H2-blockers. Today it is more and more accepted that
      duodenal ulcer is only H2-receptor antagonist refractory after a consequent
      therapy with H2-receptor antagonists in a standard dose or high doses for at
      least 2-3 months. The aims of therapy is refractory ulcers include as in non
      refractory ulcers healing, pain relief and relapse prophylaxis. Often there is
      the choice to switch to a more potent antisecretory drug. E.g. ranitidine 300
      mg/die was administered successfully in so-called cimetidine resistant ulcers.
      The specific acid inhibitory profile of omeprazole characterises this substance
      as a promising alternative in the treatment of H2-receptor antagonist refractory
      ulcers. In a large controlled clinical therapeutic trial with omeprazole 20
      mg/die versus ranitidine 300 mg/die, however, no significant differences were
      observed in the 2- and 4-weeks healing rates. In two further controlled studies
      including 99 and 50 patients respectively treated with omeprazole 40 mg/die or
      cimetidine 800 mg/die and ranitidine 300 mg/die significantly higher healing
      rates were observed in favour of omeprazole. H2-blocker resistant ulcers are
      characterised by frequent and rapidly developing relapses. In this cases further
      treatment with H2-blockers in a two- or threefold daily dose has proved to be
      effective treatment. The administration of high omeprazole doses (40-60 mg/die)
      has also produced very convincing clinical results. If the above mentioned
      therapeutic measure do no provide adequate therapeutic results surgical
      procedures--usually resection--are indicated.

PMID- 1351331
TI  - 46th Congress of the Scandinavian Orthopedic Association combined with the
      Hellenic Orthopedic Association. Malmo, Sweden, June 2-5, 1992. Abstracts.

PMID- 1351329
TI  - [Therapeutic possibilities, respective implications in silent ischemia].
AB  - In principle, all forms of treatment applied in patients with symptomatic
      coronary heart disease may likewise be used in silent myocardial ischemia. Based
      on Bayes' theorem, therapeutic measures may only be applied in patients with a
      positive exercise ECG with a high likelihood of coronary heart disease, and/or
      with myocardial ischemia revealed by another, ECG-independent method, such as,
      for example, thallium-scintigraphy. As symptomatic improvement cannot be expected
      in patients with silent myocardial ischemia, therapeutic efficacy can only be
      documented by an improvement in prognosis. Results of controlled randomized
      trials are not available in silent myocardial ischemia; therapeutic
      recommendations can, therefore, only be based on analogous results obtained in
      patients with symptomatic forms of the disease. Apart from reduction of the known
      risk factors of coronary heart disease, aspirin may be given to all patients at
      risk. Among the antiischemic antianginal drugs, beta-receptor blocking agents
      without intrinsic-sympathomimetic activity may be expected to improve prognosis.
      In asymptomatic patients with left-stem stenosis and three-vessel disease with
      impaired left-ventricular function (also, in two-vessel disease with a stenotic
      dominant LAD) aorto-coronary bypass surgery may be considered in order to improve
      prognosis.

PMID- 1351332
TI  - N-methyl-D-aspartate (NMDA) depolarizes glutamate-insensitive neurones in the
      superficial dorsal horn.

PMID- 1351330
TI  - [Breast carcinoma in pregnancy. Clinical, histological and immunohistochemical
      findings].
AB  - The hormonally induced changes in the breast during pregnancy make the diagnosis
      of breast cancer difficult. Furthermore, examinations during pregnancy tend to
      concentrate only on the pregnancy itself. In this report the clinical,
      pathological and immunohistochemical results from 7 patients with breast cancer
      during pregnancy are presented. All women first noticed the tumor by self
      examination. The time periods between discovery of the tumor and medical
      treatment were between 4 and 22 weeks. An overexpression of c-erbB-2-oncogene
      coded transmembrane protein p185 could be demonstrated in 4 cases. Of the seven
      patients, 5 have already passed away. Three of the deceased had p185-positive
      tumors, and died 4, 8 and 21 months after diagnosis. The two p185-negative
      patients lived 34 and 65 months post diagnosis. Despite the small amount of cases
      presented, a trend can be seen that p185 may be an additional prognostic factor
      for breast cancer in pregnancy.

PMID- 1351333
TI  - Rationalizing neuroleptic polypharmacy in chronic schizophrenics: effects of
      changing to a single depot preparation.
AB  - This study investigated the effects of transferring patients on combined depot
      and oral neuroleptics to a single depot preparation; a secondary objective was to
      assess the effects of transferring patients from one depot neuroleptic to
      another. It was found that, whereas transferring from one depot preparation
      (flupenthixol) to another (fluphenazine) had no clear disadvantage for the
      patients, changing over from a combined oral and depot (fluphenazine) regimen to
      equivalent doses of depot alone resulted in an unacceptably high rate of relapse.
      The reasons for this may relate to either the unique pharmacokinetics of these
      drugs or subtle qualitative differences between them. It is suggested that
      caution is necessary whenever attempts are made to rationalize polypharmacy in
      schizophrenic patients.

PMID- 1351334
TI  - Neuroleptic medication and reduced risk of prostate cancer in schizophrenic
      patients.
AB  - A decreased incidence of cancer of the prostate has been demonstrated in a cohort
      of 6168 chronic schizophrenic patients followed up from 1957 to 1984. A case
      control study was performed based on this cohort to determine the possible
      influence of neuroleptic treatment and other factors on the risk of developing
      prostate cancer. Thirty-eight male schizophrenic patients who had developed
      prostate cancer during the observation period were compared with 76 age- and sex
      matched controls from the same cohort. The only significant association was that
      of a reduced risk of prostate cancer among those who had been treated with a
      cumulative dose of high-dose phenothiazines (primarily chlorpromazine) of 15 g or
      more. These patients had been treated with an average daily dose of 145 mg
      chlorpromazine for an average of 12.5 years. No other significant risk factors
      were identified.

PMID- 1351335
TI  - [Collagenous colitis: clinical and histologic improvement after sulfasalazine and
      topical betamethasone].
AB  - We here by report a case of a 42 year-old white woman with an eight-year history
      of watery diarrhea where the rectal biopsies performed in endoscopically normal
      mucosa led to the diagnosis of collagenous colitis, characterized histologically
      by a thickening of the colonic subepithelial basement membrane. A brief review of
      the current etiopathogenic concepts of this entity is done and the importance of
      performing rectal biopsies in patients with unexplained diarrhea and normal
      appearing colon mucosa is stressed. A clinical improvement following therapy with
      Sulfasalazine and Beta-methasone enemas was found in this patient. We discuss the
      current views on the therapy and the difficulties of assessing responses to drugs
      in this condition.

PMID- 1351336
TI  - Electroacupuncture enhances activity of adrenal nucleolar organizer regions in
      ovariectomized rats.
AB  - Nucleolar organizer regions (NORs) may reflect the activity of cell
      differentiation and transcription of nucleolar rDNA; the present paper studied
      nucleolar organizer regions of the adrenal cortex to explore the regulatory
      effect of electroacupuncture (EA). Animals were divided into four groups, the
      ovariectomized electroacupuncture group (OV+EA group, n = 7), the ovariectomized
      group (OV group, n = 4), the EA group (n = 3) and the control group (CT group, n
      = 4). Number of AgNORs of 100 cells from zona fasciculata of the adrenal cortex
      in each case of the four groups was counted at random and the mean+/-SE
      (number/cell) in each group was calculated as follows: OV+EA group, 2.71 +/-
      0.26, OV group, 1.26 +/- 0.15, EA group, 1.21 +/- 0.04 and CT group, 1.48 +/-
      0.03. The mean of AgNORs in OV+EA group differed highly significantly from the
      other three groups (p less than 0.01) as tested with ANOVA and LSD method. No
      significant difference was found among the other three groups. Gross specimen
      examination showed that adrenals in the OV+EA group were significantly heavier
      than those in the other three groups (p less than 0.01). Vaginal smears showed
      that a response like estrogen-induced one with exfoliative cells appeared in the
      OV+EA group. EA had no significant effect on normal rats. The results suggest
      that EA may promote the synthesis and secretion of adrenal steriod hormones, the
      androgen of which will then be transformed into estrogen in other tissues, thus
      compensating the deficiency of estrogen induced by ovariectomy.

PMID- 1351337
TI  - Osteoelectroacupuncture in the management of vertebrogenic pain syndromes in the
      lumbar region and lower extremities.
AB  - The method for a deep electrical stimulation of the osteofibrous formations
      involved in a dystrophic process which can be identified according to the
      criterion of a palpable painfulness or by means of thermography of the projection
      of local hyperthermia sites is described. An evaluation of the results of the
      management of vertebrogenic lumbalgia and lumbo-ischialgia by using the proposed
      method of osteo-electroacupuncture (stimulation by the bipolar asymmetric
      impulses, O.I msec duration, 5-IO Hz frequency, and up to 200 microA current
      intensity) has revealed a statistically significant curtailment of the treatment
      terms and a fewer number of the recurrences when compared to the standard
      schemes.

PMID- 1351338
TI  - Bi-directional transmission of molecular information by photon or electron beams
      passing in the close vicinity of specific molecules, and its clinical and basic
      research applications: 1) Diagnosis of humans or animal patients without any
      direct contact; 2) Light microscopic and electron microscopic localization of
      neuro-transmitters, heavy metals, Oncogen C-fos (AB2), etc. of intracellular fine
      structures of normal and abnormal single cells using light or electro-microscopic
      indirect Bi-Digital O-Ring Test.
AB  - In 1985, Omura, Y. discovered that, when specific molecules were placed anywhere
      in the close vicinity of the path of a light beam (laser), their molecular
      information, as well as information on electrical & magnetic fields, is
      transmitted bi-directionally along the path of this light beam. Namely, this
      information is transmitted in the direction the light beam is projected and
      towards the direction from which the light beam is coming. This finding was
      applied to the following clinical and basic research: 1) In the past, using
      indirect Bi-Digital O-Ring Test, human or animal patients were diagnosed through
      an intermediate third person holding a good electrical conducting probe, the tip
      of which was touching the part of the patient to be examined. However, in order
      to diagnose the patient in isolation from a distance, or a dangerous or
      unmanagable unanesthesized animal, such as a lion or tiger, the author succeeded
      in making a diagnosis by replacing the metal conducting probe with a soft laser
      beam which is held by the one hand of the third person whose index finger is
      placed in close vicinity of the laser beam generated by a battery-powered
      penlight-type solid state laser generator. Thus, diagnosis within visible
      distance, without direct patient contact, became a reality. 2) Using a projection
      light microscope, by giving indirect Bi-Digital O-Ring Test while contacting with
      a fine electro-conductive probe on the magnified fine structure of normal and
      abnormal cells, various normal and abnormal intracellular substances were
      localized through a third person holding a pure reference control substance with
      the same hand that is holding the probe as an intermediary for the indirect Bi
      Digital O-Ring Test. Instead of the photon beam in a light microscope, the author
      found that, using an electron beam passing through the close vicinity of specific
      molecules of specimens in an electron microscope, the molecular information is
      transmitted to the magnified fluorescent screen, and an indirect Bi-Digital O
      Ring Test could be performed through a projected penlight-type solid state soft
      laser beam on the magnified intracellular structure through an observation glass
      window. Using the magnified fine structure of the cells, by either a light
      projection microscopic field or electron microscope, in various cancer cells of
      both humans and animals, Oncogen C-fos (AB2) and mercury were found inside of the
      nucleus. Integrin alpha 5 beta 1 was found on cell membranes and nuclear cell
      membranes of cancer cells. Acetylcholine was not found anywhere within cancer
      cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1351339
TI  - Clinical treatment of temporomandibular joint dysfunction syndrome.

PMID- 1351340
TI  - The origin of the five elements in the traditional theorem of acupuncture: a
      preliminary brief historic enquiry.
AB  - Five Xing is an important integral in the traditional theoretic basis of
      acupuncture and traditional Chinese medicine. The word Xing has been translated
      as Element. However, it actually denotes movement and activity. The word element
      implies a stationary state. Some of the evidence in ancient Chinese literature
      was reviewed to support the hypothesis that Five Xing were originally meant to be
      the Five Xing Xin (Moving Stars, i.e., Planets). By the 4th century B.C.,
      associations of the Stars with human events gradually evolved. However, between
      the 4th and the 6th century A.D., when the Taoist scholar-physicians expanded the
      Five Xing into abstractive concepts, they used the five basic materials as their
      representatives. Since they were basically alchemists and not astronomers, they
      apparently minimized the relationship between the Five Moving Stars and the human
      illnesses. It is, therefore, proposed that the usage of the word Element be
      discontinued and the word Xing be employed as is.

PMID- 1351341
TI  - [Three-dimensional computerized tomography in trauma surgery. A case
      presentation].
AB  - Three-dimensional images of bone structures can easily be reconstructed from
      computed tomography data. The technique and the advantages of contemplating
      reconstructions of bone defects in different directions are described. A special
      software programme allows to combine all data which are given by the standard CT.
      The slice diameter is two millimetres. The reconstruction shows bone surfaces in
      all required views. In traumatic and orthopaedic surgery 3-D-CT is useful in the
      analysis, detection and preoperative planning of comminuted bone injuries of the
      spine, pelvis, knee, shoulder and the calcaneus. With this technique it is
      possible to see the bone in its topographic constellation, to observe fractures
      in unusual directions and to identify fragments from each other. The surgeon gets
      a lot of additional information which is helpful to decide on the incision, the
      reduction and the fixation of fragments. Undesirable effects during operation are
      reduced, which leads to a more accurate treatment and subsequent better results.

PMID- 1351342
TI  - [Limits for recognizing linear fractures of the cranial vault in radiologic
      diagnosis].
AB  - In case of failure to detect a vault fracture in fatal head injury the physician
      is often accused of medical negligence. The material for the study consisted of a
      macerated vault with fractures in different widths. In order to detect the
      threshold of perceptibility it underwent radiographic examination taking pictures
      under different projections. Our finding is that the presence or absence of a
      radiographic fracture depends on the width and direction of the fracture.
      Therefore it is impossible to detect every single linear fracture of the vault in
      routine skull examination. Clinical and medico-legal consequences are discussed.

PMID- 1351343
TI  - [Stabilization of the injured shoulder joint with PDS cord].
AB  - A successful treatment of the acromioclavicular separation is the repair of the
      acromioclavicular and coracoclavicular (CC-)ligaments and a stable reduction of
      the acromioclavicular (AC-)joint. To avoid dangerous breakage and migration of
      the K-wire an abduction humeral splint is necessary immobilizing the injured
      shoulder for 5-6 weeks. In the years 1987-1989 40 patients suffering AC
      separation were treated (34 Tossy III separations, 4 Tossy II separations, 2
      Tossy I separations). In these cases a stable reduction was achieved by a
      transarticular K-wire fixation and a combination of AC- and CC-fixation by loops.
      In 1987 wire loop was used. In 1988 a combination of wire and Polydioxanon (PDS)
      loops was used. The PDS-loop, a slowly resorbable suture material, fixed the CC
      ligament. In 1989 the AC-joint was stabilized by a PDS-loop as well. The
      examination of 31 patients 6-24 months after the operation showed good clinical
      results no matter whether PDS-loops or wire loops were used. The advantage of the
      transarticular K-wire fixation in combination with PDS-loops was the easy
      removal, which could be done in mostly of the cases as an outpatient procedure.
      An operation of the AC-Tossy III separation on patients beyond their 4. decade
      should be well considered. A long time of treatment, remaining pain and a
      limitation of shoulder movement must be expected.

PMID- 1351344
TI  - [Drill wire osteosynthesis in subcapital humerus fractures: percutaneous or open
      procedure?].
AB  - Between 1978 and mid-1990, 135 patients suffering from dislocated, non-luxated
      fracture of the humerus at the anatomical neck (fractura colli anatomici) were
      treated by means of open or closed percutaneous drill wire osteosynthesis. Follow
      up examination after an average of 9 months did not show any significant
      differences between the two surgical approaches in 117 patients, independent of
      the shape of the fracture. However, in about 30% of the cases it was impossible
      to employ the percutaneous approach due to the presence of an obstacle to
      reduction, so that open reduction and fixation was the only choice. A great
      majority of the functional results must be considered as good, fractures of the
      tubercles having the most unfavourable prognosis independent of the surgical
      technique. It is, therefore, recommended to first try closed reduction with
      percutaneous drill wire osteosynthesis. If there are any obstacles to reduction,
      open reduction should be restored to during the surgery session.

PMID- 1351345
TI  - [Treatment of osteomyelitis and reconstructive measures in patients with war
      injuries].
AB  - 54 wartime trauma patients injured by bombs, shell splinters or rockets were
      treated between 1985 and 1989 in the Orthopaedic Clinic of RWTH Aachen. Lesions
      of the lower limbs were dominating (78%). Treatment was often tedious, and up to
      12 operations had to be performed. In 81% one extremity was injured, in 17% two
      extremities were involved. 78% of the patients were already primarily treated at
      home, mostly by amputations. 33% of the patients suffered from bone infections at
      admission. Infections were mostly caused by Staphylococcus aureus or Pseudomonas
      aeruginosa. In 41% of all patients operative treatment for osteomyelitis was
      necessary (37% sequesterectomies, 44% stabilisations with fixateur externe). In
      advanced bone infection amputations were indispensable in 28%. In 27% of our
      wartime trauma patients reconstructive surgery was performed (spongiosa
      transplantations in 91%, stabilisation with fixateur externe in 44%). In none of
      our patients treated with reconstructive surgery an amputation was necessary
      later on.

PMID- 1351347
TI  - [Capsular ligament lesions of the knee joint. 5-9 year results of surgical
      management].
AB  - 5-9 years follow-up results following 26 out of 37 operated injuries of the
      ligaments of the knee are reported. While 18 patients described the result of the
      operation as very good and good, the objective findings presented only 5 stable
      knees.

PMID- 1351346
TI  - [Early management of a fracture of the coxal end of the femur in elderly
      patients].
AB  - The demographical structure of the Federal Republic of Germany leads to an
      increasing number of very old patients in traumatology. Even minor accidents can
      cause severe injuries including operative treatment. In this retrospective study
      the data of 219 patients older than 70 years who had to undergo an operation at
      the femoral neck region are analyzed. The aim of operative management was a very
      early operation and a fixation device, that allows an immediate full weight
      bearing. Fractures of the femoral neck are stabilized by hemiarthroplasty,
      fractures of the trochanteric region with the dynamic hip screw. 90% of our
      patients could be operated within 24 hours, the mortality rate during the first
      14 days was 3%.

PMID- 1351348
TI  - [Damage to the rotator cuff. Legal expertise aspects].

PMID- 1351349
TI  - [Orofacial injuries in skateboard accidents].
AB  - In a clinical study, 25 accidents involving injuries by a fall with a skateboard
      were investigated and classified in respect of epidemiology, accident mechanism
      and injury patterns in the facial region. Accident victims are predominantly boys
      between 7 and 9 years of age. A multiple trauma involving the teeth and the
      dental system in general and the soft parts of the face is defined as a
      characteristic orofacial injury pattern in skateboard accidents. The high
      proportion of damage to the front teeth poses problems of functional and
      aesthetic rehabilitation necessitating long-term treatment courses in children
      and adolescents. Effective prevention of facial injuries may be possible by
      evolving better facial protection systems and by creating areas of playgrounds
      where skateboarders can practise safely.

PMID- 1351350
TI  - [The 96th Congress of Japanese Society of Ophthalmology. Yokohama, May 7-9, 1992.
      Abstracts].

PMID- 1351351
TI  - A review of the literature on the use of ultrasonography in schistosomiasis with
      special reference to its use in field studies. 1. Schistosoma haematobium.
AB  - This review presents an outline of the pathology resulting from Schistosoma
      haematobium infections, and the ways in which the lesions can be investigated.
      The use of ultrasonography is covered in detail. Ultrasonography can provide
      direct information about lesions in internal organs, and thus provide information
      about patterns of morbidity and about the regression of pathological changes
      after treatment. The method has the advantages that it is non-invasive, and is
      also relatively inexpensive and can be used under field conditions.
      Ultrasonography has already been used in a number of epidemiological studies in
      areas where S. haematobium is endemic. The method has proved to be feasible and
      useful. However, the methodology used for ultrasound studies has varied
      considerably, so that it is difficult to make valid comparisons between results
      obtained in different places or at different times. A standardized methodology
      for making observations and recording the results is needed if the full potential
      benefit of using ultrasound in the monitoring of schistosomiasis control projects
      is to be realised. The correlation of results obtained using ultrasound with the
      results of clinical, parasitological and other observations has been investigated
      in a number of studies, but many questions remain to be answered.

PMID- 1351352
TI  - A review of the literature on the use of ultrasonography in schistosomiasis with
      special reference to its use in field studies. 2. Schistosoma mansoni.
AB  - This review presents an outline of the pathology resulting from Schistosoma
      mansoni infections, and the ways in which it can be investigated. The use of
      ultrasonography is covered in detail. Ultrasonography can provide direct
      information about lesions in internal organs, and thus provide information about
      patterns of morbidity and about the regression of pathological changes after
      treatment. The method is non-invasive, and can be used under field conditions.
      Ultrasonography is valuable for the study of hepatosplenic pathology, to detect
      lesions such as the development of periportal fibrosis and the enlargement of the
      portal vein, which can indicate the development of portal hypertension. This may
      lead to a severe outcome, including bleeding from oesophageal varices, which is a
      principal cause of death from S. mansoni infection. A problem with the use of
      ultrasonography is that the mild lesions likely to be observed in population
      surveys are not always easy to assess. Ultrasonography has already been used in a
      number of epidemiological studies of S. mansoni infection, and has proved to be
      feasible and useful. However, the methodology used for ultrasound studies has
      varied considerably, so that it is difficult to make valid comparisons between
      results obtained in different places or at different times. A standardized
      methodology for making observations and recording the results is needed if the
      full potential benefit of using ultrasound in the monitoring of schistosomiasis
      control projects is to be realised.

PMID- 1351353
TI  - A review of the literature on the use of ultrasonography in schistosomiasis with
      special reference to its use in field studies. 3. Schistosoma japonicum.
AB  - This paper gives a brief description of the pathology resulting from Schistosoma
      japonicum infection, and ways in which it can be investigated. It then reviews
      reports of the application of ultrasound in investigating lesions in
      schistosomiasis japonica, including papers published in Chinese and Japanese.
      Ultrasonography has been widely used for the diagnosis of schistosomiasis and for
      the investigation of pathological changes resulting from the infection. Marked
      and characteristic changes are observed in the structure of the liver parenchyma
      in advanced disease. Chronic pathology may be seen as a result of past infection.
      Animal studies have been used to compare ultrasound images with actual
      pathological changes. Ultrasonography can also be used to detect early changes,
      for example periportal fibrosis, which can indicate the development of portal
      hypertension. The problem of differential diagnosis is discussed.

PMID- 1351355
TI  - The use of diagnostic ultrasound in schistosomiasis--attempts at standardization
      of methodology. Cairo Working Group.
AB  - This paper summarises the conclusions of a workshop held in Cairo in 1990 to
      discuss the standardization of the use of diagnostic ultrasound in
      schistosomiasis. For epidemiological purposes, it is very important that
      ultrasound examinations should be carried out and recorded in a standardized way,
      in order to ensure that results obtained in different places and at different
      times can be compared. The workshop did not attempt to produce final
      recommendations, but it did make tentative proposals in a form suitable for field
      testing. The paper discusses the general problems involved in carrying out and
      recording ultrasound examinations in a standardized way. The special points
      involved in assessing lesions due to the three main forms of schistosomiasis are
      then considered in detail. Methodology that can be used in epidemiological work
      with large numbers of people is emphasised.

PMID- 1351354
TI  - Studies on ultrasonographic diagnosis of schistosomiasis japonica in China--a
      review of selected Chinese studies.
AB  - Diagnostic ultrasound has been used in China since the early 1960's in the
      investigation of Schistosoma japonicum infection. This paper presents an overview
      of selected papers from the Chinese literature on the use of ultrasound in
      studies of schistosomiasis japonica, and briefly reports the results of studies
      not yet published elsewhere. The method is compared with other diagnostic
      procedures, and the benefits and limitations of using ultrasound are discussed.

PMID- 1351356
TI  - Liver ultrasound findings in a low prevalence area of S. japonicum in China:
      comparison with history, physical examination, parasitological and serological
      results.
AB  - The paper describes a study carried out in a community in Dongdian township,
      Anhui Province, People's Republic of China. Medical history and the results of a
      physical examination, ultrasound investigation, parasitological and serological
      tests for Schistosoma japonicum infection were compared in 661 persons of 169
      households. A lack of correlation between parasitological and serological
      indicators of infection and morbidity was observed in this area of low (6.4%)
      prevalence and intensity of infection. The prevalence of abnormal ultrasound
      findings in the liver in this population was high (56%), and was significantly
      higher than the prevalence of S. japonicum infection. The abnormal ultrasound
      findings correlated with a history of schistosomiasis, and the correlation
      increased significantly according to the number of times treated and the time
      since the last treatment, which suggested that past parenteral treatment has a
      role in the high rate of abnormal liver ultrasound findings. The significant
      correlation between the qualitative and quantitative serological results and
      abnormal ultrasound parenchymal patterns suggests that cross-reactivity between
      the etiology of the parenchymal disease and these tests is occurring. The
      presence of HBsAg correlated with the composite presence of ultrasound
      abnormalities of the liver parenchyma: increased echogenicity, periportal
      fibrosis and/or nodules and irregular fibrosis, whereas a normal ultrasound
      pattern was associated with the absence of HBV antigenemia.

PMID- 1351357
TI  - Inter-observer variance in ultrasonographical assessment of Schistosoma mansoni
      related morbidity in young schoolchildren.
AB  - 49 Sudanese schoolchildren aged 6-9 years with Schistosoma mansoni infection were
      ultrasonographically examined by two independent observers in a double-blind
      fashion. The first observer recorded normal appearance of the liver in 23 cases,
      whereas the second observer recorded the appearance as normal in 33 cases. There
      were 23 concordant observations. For Grade I periportal fibrosis (PF), 13
      observations were concordant. PF Grade II was rarely observed (2 versus 3 cases),
      and Grade III was not recorded at all. In total, 38 out of 49 observations were
      concordant (77.5%). These preliminary data from two ultrasound observers, from
      observations on a limited number of patients, can be seen as an indication of a
      potential inter-observer variation of around 20% for the distinction between the
      absence of PF and a low level of PF.

PMID- 1351358
TI  - Ultrasound in schistosomiasis--a critical look at methodological issues and
      potential applications.
AB  - This is the concluding paper of a series on the use of diagnostic ultrasound in
      the investigation of schistosomiasis. An earlier chapter in the volume discussed
      standardization of the methodology, and of recording, when ultrasound is used for
      epidemiological purposes. The present paper discusses some other requirements for
      obtaining ultrasound data which can be used to make valid comparisons within and
      between studies. Since there is an inherent variability in the interpretation of
      results from ultrasound images, quality control and the training of observers are
      both essential. It is also necessary to collect more information for each endemic
      setting about possible concomitant diseases which might lead to misinterpretation
      of results. Furthermore, the analysis of the data obtained must be uniform if
      valid comparisons are to be made. A final section considers applications of
      ultrasonography in research and control programmes. The technique should make it
      possible to obtain a better understanding of the extent and distribution of organ
      damage due to schistosomal infection in different geographical areas, and of the
      way in which lesions develop over time, or may regress in response to treatment.
      Since ultrasonography will always remain a relatively labour-intensive and
      expensive technique, it is necessary to establish, in different settings, how its
      findings correlate with the results of parasitological, serological and
      biochemical tests. The ultimate aim is to build up a body of information on the
      potential of ultrasonography, in combination with other procedures, in the
      various possible approaches to morbidity control.

PMID- 1351359
TI  - Advances in echocardiography: a view toward the year 2000. Symposium.
      Williamsburg, Virginia, September 12-14, 1991.

PMID- 1351360
TI  - Dehydroepiandrosterone: antiglucocorticoid action in mice.
AB  - The acute effect of dehydroepiandrosterone (DHEA) and its conjugate, DHEA-sulfate
      (DHEA-S) on glucocorticoid action was tested in vivo using male Swiss-Webster
      mice. The authors found that DHEA and DHEA-S significantly inhibited induction of
      hepatic tyrosine aminotransferase activity, although the former was more potent.
      This inhibition was dose- and time-dependent and was not demonstrable with other
      steroids. The same inhibitory effect of DHEA was seen with kidney tyrosine
      aminotransferase induction, as well as with liver and kidney ornithine
      decarboxylase enzyme activity, another glucocorticoid-induced enzyme. The
      conclusion is that DHEA acts acutely as an antiglucocorticoid and exerts its
      effect in different glucocorticoid-sensitive systems.

PMID- 1351361
TI  - On some technical aspects of direct DNA diagnosis of the fragile X syndrome.
AB  - Direct DNA analysis of fragile X [Fra(X)] mutations has already shown its clear
      superiority for postnatal and prenatal diagnosis of the disorder and for carrier
      detection. However, it is of great importance to have conditions which guarantee
      optimal reliability and sensitivity. Some mutations may be more difficult to
      detect, especially in female carriers: this is the case for small amplifications
      of the CGG repeat (premutations) or for smears which can be generated by the
      instability of the full mutation in somatic tissues. We present the various
      alternatives (probe/enzymes combinations) for Southern blot based diagnosis, the
      possible artefacts and our detailed experimental protocol, which has given
      excellent results on a large number of families. While detection of
      amplification, using for instance EcoRI, appears sufficient for initial testing
      of mentally retarded patients, once the fra(X) diagnosis has been established, we
      favor the use of an EcoRI+EagI digest, which detects both amplification and
      abnormal methylation, for analysis of the family, including carrier detection and
      prenatal diagnosis. We discuss the place of proposed PCR based techniques for
      detection of mutations, or for indirect tracking using polymorphic
      microsatellites in the immediate vicinity of the fra(X) locus.

PMID- 1351363
TI  - Direct DNA analysis of fragile X syndrome in Spanish pedigrees.
AB  - Eleven complete Spanish pedigrees with fragile X syndrome were analysed by
      Southern blotting with the DNA probe StB12.3 previously isolated and described by
      Oberle et al. [1991]. This probe allowed the direct detection of affected males
      and carrier females and was able to distinguish between normal males and normal
      transmitting males (NTMs). One hundred and twenty three individuals were
      analyzed, 115 from the pedigrees and 8 from the general population. Five mosaic
      cases were found (4 males and one female) showing both the premutation and the
      full mutation. One half of the females with the full mutation were mentally
      retarded but no female with mental retardation carried the premutated pattern,
      suggesting that the absence of the full mutation in females is a very good
      criterion for pre-or postnatal diagnosis of normal mental status.

PMID- 1351362
TI  - Characterization of new PCR based markers for mapping and diagnosis: AC
      dinucleotide repeat markers at the DXS237 (GMGX9) and DXS102 (cX38.1) loci.
AB  - Genomic insert DNAs from 45 probes representing 113.4 kb of the X chromosome were
      screened for AC dinucleotide repeat sequence. Two new AC repeat sequences were
      identified with length polymorphism based on variation in repeat copy number. One
      at DXS237 exhibits 44% heterozygosity and is potentially useful for rapid
      diagnosis and mapping of X-linked disorders in Xp22.3. The other, at DXS102 in
      Xq26, has 71% heterozygosity. This marker will improve accuracy of diagnoses by
      linkage for families with Borjeson-Forssman-Lehmann syndrome. Review of the
      literature has identified 31 PCR based markers on the X chromosome, with minimum
      heterozygosity of 50%, applicable to the mapping and diagnosis of X-linked
      disorders.

PMID- 1351365
TI  - Linkage and risk assessment in fragile X families using new DNA probes at Xq27.
AB  - Until recently few polymorphic loci had been genetically mapped close to the
      fragile X syndrome locus [FRAXA]. Six polymorphic loci, DXS369, DXS297, DXS296,
      DXS304, IDS and DXS374, have now been mapped closer to the fragile X FRAXA than
      in the present study. We report the results of genetic linkage analysis of 32
      fragile X [fra(X)] families using 12 polymorphic loci including these new
      markers. Cytogenetic and molecular data were combined in two-point linkage
      analysis for the estimation of lod scores and carrier probabilities in potential
      carriers. Combined with results from previous studies, recombination fractions
      (0) corresponding to the maximum lod scores (Z max) were obtained for each of the
      12 loci versus FRAXA. Recombination fractions between marker loci in the families
      were also calculated. The data were evaluated to determine the efficacy of using
      the strategy suggested by Suthers et al. (1991a) for molecular studies in fra(X)
      families. The large proportion of females heterozygous for at least one locus
      (83%) and of females heterozygous for flanking loci (60%) indicate that this is a
      very useful diagnostic strategy. Use of these new marker loci substantially
      changed the carrier risk estimates for members of 7 of the 32 families from the
      risk estimates previously calculated on the basis of less closely linked probes
      available prior to 1989.

PMID- 1351366
TI  - Abnormal isoform of prion proteins accumulates in the synaptic structures of the
      central nervous system in patients with Creutzfeldt-Jakob disease.
AB  - A new method, which enabled the first immunohistochemical documentation of
      abnormal prion protein (PrP) in all patients with Creutzfeldt-Jakob disease
      (CJD), was established. This method designated as "hydrolytic autoclaving"
      revealed punctate PrPCJD stainings around the neuronal cell bodies and dendrites
      in CJD brains. These punctate stainings were almost identical with that of
      synaptophysin, suggesting PrPCJD accumulations in the synaptic structures.
      Subcellular fractionation revealed that prion protein in Creutzfeldt-Jakob
      disease (PrPCJD) was most concentrated in the synaptosomal fraction. In CJD
      patients with a long clinical course, synaptophysin immunoreactivity decreased,
      and synaptic PrPCJD accumulated with a wider distribution. These results suggest
      that synaptic PrPCJD accumulations might be responsible for the neuronal
      dysfunction and degeneration in CJD.

PMID- 1351364
TI  - Carrier detection of the fragile X syndrome with flanking RFLP markers and
      linkage analysis.
AB  - Linkage analysis was performed in 34 fragile X (fra(X)) families in order to
      study the efficiency of carrier detection using the restriction fragment length
      polymorphisms (RFLPs) closely linked to fra(X) locus (FRAXA). The marker loci
      used were F9, DXS105, DXS98, DXS369, DXS297 and DXS477 proximally and DXS465,
      DXS296, DXS304, DXS52 and F8C distally to FRAXA. Flanking heterozygosity was
      achieved in 60% of the females with a combination of 3 restriction enzymes and 6
      closest RFLP markers. When adding more distant markers and other restriction
      enzymes to the analysis, the proportion of females heterozygous for flanking
      polymorphisms increased to 96%. With RFLP-analysis most (85/91) females at high
      risk of being a carrier could be separated clearly into 2 groups: those with a
      very low and those with a very high risk. The 6 cases with a recombination
      between flanking markers did not benefit from RFLP-analysis.

PMID- 1351367
TI  - Dose-related effects of doxazosin on plasma lipids and aortic fatty streak
      formation in the hypercholesterolemic hamster model.
AB  - Doxazosin, an alpha 1-adrenergic inhibitor, has been shown to decrease
      hypertension and plasma lipids, especially total cholesterol (TC) and low-density
      lipoprotein cholesterol (LDL-C), thus reducing certain risk factors associated
      with increased incidence of cardiovascular disease. One preliminary report
      indicated that the decrease in LDL-C in hypercholesterolemic hamsters treated
      with doxazosin was associated with a reduction in fatty streak formation.
      However, since the effects of doxazosin on plasma lipids, aortic fatty streak
      development, or the relationship between the two have not been studied in a dose
      dependent manner, these effects were further investigated over varying doses of
      doxazosin (0, 1, 5, 10, and 20 mg/kg body wt/day) during a 10-week period.
      Doxazosin administration was associated with a dose-dependent decrease in LDL-C
      of 2%, 29%, 52%, and 60%, whereas the degree of fatty streak formation was
      reduced 11%, 45%, 76%, and 92% compared with controls, with the first
      statistically significant decrease for both parameters at the 10 mg/kg dose.
      Significant correlations between LDL-C concentrations and fatty streak area
      suggest that doxazosin altered aortic lipid infiltration primarily by its effect
      on plasma lipids. However, the 20 mg/kg dose of doxazosin significantly decreased
      lesion area compared with the 10 mg/kg dose without a further effect on plasma
      lipid concentrations. Three animals at these higher doses demonstrated no
      stainable lipid inclusions while maintaining plasma lipid values similar to their
      cohorts. These exceptions to the lipid-lesion relationship raise the possibility
      of additional effects of doxazosin, which may occur independent of or in concert
      with lipoprotein cholesterol lowering, on lesion formation.

PMID- 1351368
TI  - HUT 78 T cells bind to noncytokine-stimulated keratinocytes using a non-CD18
      dependent adhesion pathway.
AB  - The initial in vitro observation that cultured keratinocytes, when treated with
      cytokines such as gamma interferon, increased the binding of T lymphocytes,
      opened up a whole new avenue of research to understand epidermal trafficking
      patterns in inflammatory skin diseases. A growing body of data strongly supports
      the in vivo role of lymphocyte-function-associated antigen-1 (CD18) expression by
      T cells in the binding to intercellular adhesion molecule-1 (CD54) expressing
      keratinocytes. To further explore the molecular basis for other possible adhesive
      interactions involving T cells and skin-derived cellular constituents, the
      authors used 2 cell lines (HUT 78 cells and Jurkat cells) and added them to
      multipassaged human keratinocytes, fibroblasts, and melanocytes. The skin-derived
      cells were treated with cytokines alone, or in combination, with a phorbol ester.
      HUT cells were capable of binding to keratinocytes in the absence of pretreatment
      with cytokines at 25 degrees C, which was not inhibited by anti-CD18 antibodies,
      or sensitive to reducing the temperature of the adhesion assay to 7 degrees C.
      Fibroblasts and melanocytes also constitutively bound HUT cells, but the binding
      to fibroblasts was highly temperature-sensitive. When keratinocytes were
      pretreated for 48 hours with gamma interferon plus phorbol ester, a
      "superadhesive" state was induced, resulting in a synergistically increased
      binding ability of both HUT cells and Jurkat cells. This effect was related to
      quantitative increases in keratinocyte intercellular adhesion molecule-1
      expression. Several other clear-cut qualitative and quantitative differences were
      detectable in the ability of HUT cells and JS cells to bind to nontreated and
      cytokine/phorbol ester-treated keratinocytes, fibroblasts, and melanocytes. These
      results emphasize the complexity of molecular associations underlying T-cell
      trafficking patterns, potentially operative in the dermal and epidermal
      compartments of the skin.

PMID- 1351369
TI  - Thrombospondin and other possible related matrix proteins in malignant and benign
      breast disease. An immunohistochemical study.
AB  - Thrombospondin (TSP), which plays an important hemostatic role, is a 450-kd
      cytoadhesive protein present in the alpha granules of platelets. In vitro
      experiments using cultured malignant cells suggest that it may help to mediate
      malignant cell attachment to extracellular matrix and may be important in cancer
      invasiveness. The authors studied a group of malignant and benign breast tissues
      for the expression of TSP and provide evidence that TSP may have a role in tumor
      invasiveness. Using immunohistochemical techniques, the authors found in 48 fresh
      specimens of breast carcinoma that TSP stained strongly in the desmoplastic
      stroma or at the basement membrane associated with the malignant ductal
      epithelium. Tumor cells abutting these tissues revealed cytoplasmic staining for
      TSP. Stronger TSP staining was seen in the poorly differentiated tumors. These
      findings were compared with those of normal and benign breast tissue, which
      showed no TSP staining apart from reactivity in the large distended cysts of
      fibrocystic disease and faint staining in the stroma of fibroadenomas. Staining
      for integrin was positive in lymphocytes of both malignant and benign breast
      disease and equivocally also in the stromal cells of the breast cancer tissue.
      Immunoreactivity to TSP in tissues was also compared with that of fibronectin,
      laminin, and collagen type I, III, and IV. The overall findings suggest that
      thrombospondin may have a role in the tumor biology of invasiveness.

PMID- 1351370
TI  - Immunocytochemistry of paraneurons in the female urethra of the horse, cattle,
      sheep, and pig.
AB  - The aim of this study is to describe the presence of neuroendocrine (NE) cells
      (paraneurons), producing biogenic amines and/or peptidergic hormones, in the
      female urethra of cattle, sheep, pigs, and horses, by means of histochemical and
      double labeling immunofluorescent techniques. 5-Hydroxy-tryptamine-, chromogranin
      A-, cholecystokinin- and somatostatin-containing NE cells are present in the
      urethral epithelium of all the species studied, with the unique exception of the
      lack of somatostatin cells in the horse. Paraneurons containing 5
      hydroxytryptamine colocalized with chromogranin A or cholecystokinin were also
      found in all subjects. Such active substances are hypothesized to play a role in
      the contraction of the urethral musculature, emission of urogenital fluids, and
      inhibition of endocrine and exocrine secretions.

PMID- 1351371
TI  - Low-dose trimethoprim-sulfamethoxazole prophylaxis for toxoplasmic encephalitis
      in patients with AIDS.
AB  - OBJECTIVE: To determine the efficacy of low-dose trimethoprim-sulfamethoxazole
      (trimethoprim, 160 mg plus sulfamethoxazole, 800 mg; one tablet twice daily, 2
      days per week) as primary prophylaxis against toxoplasmic encephalitis in
      patients with human immunodeficiency virus (HIV) infection and previous
      Pneumocystis carinii pneumonia. DESIGN: A retrospective study. SETTING: Tertiary
      referral teaching hospital. PATIENTS: During a 3-year period after primary
      episodes of P. carinii pneumonia, 60 patients received trimethoprim
      sulfamethoxazole, and 95 patients received pentamidine (aerosolized in 78
      patients and intravenous in 17 patients) as secondary prophylaxis. RESULTS: No
      patient in the trimethoprim-sulfamethoxazole group and no patient seronegative
      for Toxoplasma gondii developed toxoplasmic encephalitis, compared with 12 of 36
      (33%; 95% Cl, 19% to 51%) seropositive patients in the pentamidine group
      (trimethoprim-sulfamethoxazole compared with pentamidine, P = 0.008). A
      significant difference was seen in the time to development of toxoplasmic
      encephalitis between the trimethoprim-sulfamethoxazole group (no case at 1153
      days) and the pentamidine group (median time, 460 days) (P = 0.004). Neither the
      CD4+ lymphocyte count at the start of prophylaxis nor zidovudine therapy during
      the period of prophylaxis influenced the rate of toxoplasmic encephalitis in any
      group. CONCLUSIONS: Low-dose trimethoprim-sulfamethoxazole (four tablets per
      week) appears to be effective prophylaxis against toxoplasmic encephalitis in HIV
      infected patients with previous P. carinii pneumonia. A prospective, randomized,
      controlled study is needed to further evaluate these findings.

PMID- 1351373
TI  - Ontogenetic and Phylogenetic Mechanisms of Neuroimmunomodulation. From Molecular
      Biology to Psychosocial Sciences. 1st International Congress of the International
      Society for Neuroimmunomodulation. Florence, Italy, May 25-28, 1990.

PMID- 1351372
TI  - Gold therapy for rheumatoid arthritis.

PMID- 1351374
TI  - Changes in thymocyte subsets induced by estradiol administration or pregnancy.

PMID- 1351375
TI  - Modulation of experimental allergic encephalomyelitis by somatostatin.

PMID- 1351376
TI  - Effects of social separation on immune function and brain neurotransmitters in
      cebus monkey (C. apella).

PMID- 1351377
TI  - Stress-induced alteration of immune function. Diversity of effects and
      mechanisms.

PMID- 1351378
TI  - Sympathetic nervous system and macrophage function.

PMID- 1351379
TI  - [Langerhans cell in epidermotropic cutaneous T-cell lymphoma. Current data].

PMID- 1351380
TI  - Anticoccidial activities of 7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine
      and other alpha 2 adrenergic agonists.
AB  - Activity against the coccidial pathogen Eimeria tenella in chickens has been
      discovered among alpha 2 adrenergic agonists. The clonidine analog 7-bromo-N-(2
      imidazolidinylidene)-1H-indazol-6-amine was active in feed at 7.5 ppm, a
      concentration similar to the use levels of potent commercial agents, e.g.,
      maduramicin. Additional alpha 2 agonists were also found to have anticoccidial
      activity, for example, the catecholamine nordefrin, which is chemically unrelated
      to clonidine. However, alpha 1 agonists and alpha antagonists were inactive.
      These observations imply that anticoccidial effects reflect involvement of a
      receptor with the characteristics of the vertebrate alpha 2 adrenoceptor. alpha 2
      agonists that permeate the blood-brain barrier (like clonidine) inhibit feed
      intake at efficacious levels, whereas those that are restricted to the peripheral
      compartment (such as catecholamines) do not inhibit feed intake as much. Hence,
      anticoccidial efficacy may be a peripheral adrenergic effect whereas depression
      of feed intake is likely centrally mediated.

PMID- 1351382
TI  - Enhancement of gamma-glutamylcysteine synthetase mRNA in rat kidney by methyl
      mercury.
AB  - Glutathione (GSH), a major cellular antioxidant, is elevated 2- to 3-fold in
      kidneys of rats during prolonged treatment with mercury as methyl mercury
      hydroxide (MMH). Increased renal GSH is accompanied by a dose- and time-related
      elevation in the relative abundance of mRNA hybridizable to a cDNA probe which
      encodes renal gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme
      in GSH synthesis. Renal GCS mRNA is maximally elevated 4.4-fold at 3 weeks
      following initiation of MMH treatment. Enhancement of GSH and GCS mRNA content
      corresponds to a relative sparing of renal cells from oxidative tissue damage
      during MMH exposure. These observations suggest that increased synthesis of GSH
      at the genetic level occurs as an initial adaptive response to mercury-induced
      oxidative stress in kidney cells.

PMID- 1351381
TI  - Further investigation of anticoccidial activity of 7-bromo-N-(2
      imidazolidinylidene)-1H-indazol-6-amine.
AB  - The clonidine analog 7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine
      exhibits potent activity against Eimeria tenella infections in chickens. Disease
      control was abrogated by a selective alpha 2 antagonist, which is consistent with
      the dependence of such activity upon binding to receptors with characteristics of
      the vertebrate alpha 2 adrenoceptor. Lack of significant activity against the
      parasite in tissue culture and our inability to detect significant binding of
      alpha 2 adrenergic ligands to E. tenella imply that the anticoccidial action may
      be an indirect effect mediated by the host. Efficacy varied, depending upon the
      Eimeria species, being greatest for the cecal species E. tenella and less for the
      intestinal species. The effects described differ substantially from previous
      accounts of adrenergic actions on parasitic protozoa. The evidence suggests that
      we have observed a new mechanism of action for antiparasitic drugs.

PMID- 1351383
TI  - [Progress in oncogene and antioncogene research].
AB  - Recent progress in molecular biology of cancer revealed that mutations which
      potentiate the activities of proto-oncogenes create the oncogenes to force the
      growth of tumor cells. On the other hand, inactivation of antioncogenes results
      in the generations of tumor cells. The progression of many tumors to full
      malignancy requires both types of changes of the tumor cell genome.

PMID- 1351385
TI  - [The current status of clinical research on impotence].

PMID- 1351384
TI  - [C-erb B-2 protein in the sera of breast cancer patients].

PMID- 1351386
TI  - [Plasma neuropeptides in affective and anxiety disorders].
AB  - The levels of Neurotensin, VIP, Somatostatin, beta-endorphin and Bombesin have
      been investigated in plasma of 16 depressed and 20 anxious patients. VIP and
      Neurotensin were found significantly decreased in patients vs a group of 20
      controls. Neurotensin levels returned to normal values after recovery. There were
      no significant differences from the normal in the concentrations of Somatostatin,
      beta-endorphin and Bombesin in the disease groups.

PMID- 1351388
TI  - International Congress on Vitamins and Biofactors in Life Science.

PMID- 1351389
TI  - Vitamin D research--First International Congress on Vitamins and Biofactors in
      Life Sciences.

PMID- 1351387
TI  - Characterization of field isolates of suid herpesvirus 1 (Aujeszky's disease
      virus) as derivatives of attenuated vaccine strains.
AB  - Field isolates of suid herpesvirus 1 (Aujeszky's disease virus) from Poland and
      Hungary were identified by restriction fragment pattern analysis as derivatives
      of attenuated vaccine strains. The Polish isolates were found to be related to
      the BUK-TK-900 strain (Suivac A) which is widely used as a live vaccine in
      Poland, and the Hungarian isolates were related to the Bartha K-61 vaccine strain
      widely used in Hungary. Pigs experimentally infected with derivatives of BUK-TK
      900 or BUK-TK-900 itself were found to develop gI-antibodies, while pigs infected
      with derivatives of Bartha K-61 showed a gI-negative response.

PMID- 1351390
TI  - Vitamin K research--First International Congress on Vitamins and Biofactors in
      Life Sciences.

PMID- 1351391
TI  - Structure-function studies of HIV-1: influence of long terminal repeat U3 region
      sequences on virus production.
AB  - DNA sequence analyses of several human immunodeficiency virus (HIV) isolates
      revealed extensive genetic diversity in the env gene and, to a lesser extent, in
      other regions of the viral genome, including the long terminal repeat (LTR)
      sequences. Since the LTRs contain elements responsible for the control of
      transcription, the difference in the LTR region may play a crucial role in the
      overall replication rate of HIV. To evaluate the role of the LTR, we have
      constructed a number of infectious hybrid HIV molecular clones containing LTRs
      from different proviral DNAs linked to the body of the viral genome, and analyzed
      them in a transient expression system. Both parental and hybrid proviral DNAs
      were transfected into human rhabdomyosarcoma cells for monitoring virus
      production. Proviral DNA designate pZ6 (HIVZr6) showed a high level of virus in
      the medium of the transfected culture in comparison to the pHXB2 (HIVHTLV-III)
      and pARV (HIVSF-2) DNAs. Hybrid proviral DNAs containing viral genes from pZ6,
      linked to LTR U3 sequences of pHXB2 and pARV at the 5' end, showed virus
      production similar to the levels observed with pZ6. These results indicate that
      the extent of virus production does not correlate with the LTR U3 sequences, and
      may involve other regions of the viral genome.

PMID- 1351392
TI  - Cellular aspects of early T-cell development.
AB  - Although the nature of the precursor cells seeding the thymus is still uncertain,
      their immediate progeny in the adult murine thymus have now been isolated. These
      lymphoid-restricted, prothymocyte-like cells express CD4, but neither CD4 nor CD8
      seem to be involved in the early steps of T-cell development. Cytokines produced
      by stromal cells are likely to be involved in intrathymic T-cell development, but
      interleukin-2 and interleukin-4 do not appear to be required. There is still no
      satisfactory cell-culture model of intrathymic T-cell development. Current
      culture systems reflect only fragments of the process, or are models of
      extrathymic developmental pathways.

PMID- 1351393
TI  - Thymic selection.
AB  - The ability of T cells to recognize foreign antigens, distinguish them from self
      antigens, and regulate immune responses depends largely on which of the vast
      array of different T-cell receptors they display on their surface, the so called
      T-cell repertoire. Two selection processes, positive and negative selection,
      operate on developing T cells and allow only a subset of all possible T cells to
      differentiate. New developments in transgenic mouse technology and the study of T
      cell signalling are unravelling these fascinating processes.

PMID- 1351394
TI  - Extrathymic T-cell selection.
AB  - The T-cell repertoire is formed during T lymphocyte maturation in the thymus.
      There is, however, increasing evidence that there are additions to, and
      modifications of, this repertoire by extrathymic events. Most importantly, mature
      peripheral T cells are not only susceptible to activation signals but also to
      tolerance induction upon encounter of extrathymic antigen. An understanding of
      these inactivation processes should result in strategies for specific
      immunosuppression in organ transplantation and autoimmune diseases.

PMID- 1351395
TI  - Immunohistochemical evidence for coexistence of methionine-enkephalin and
      tyrosine hydroxylase in neurons of the locus coeruleus complex projecting to the
      spinal cord of the cat.
AB  - Previous studies have revealed the presence of pontospinal neurons with either
      methionine-enkephalin- or tyrosine hydroxylase-like immunoreactivity in the
      dorsolateral pontine tegmentum of the cat. Using a combined fast blue retrograde
      transport technique and simultaneous immunofluorescence histochemistry, the
      present study was designed to reveal the coexistence of enkephalin and tyrosine
      hydroxylase in cat coerulospinal neurons and to determine if and to what extent
      the coerulospinal pathway is heterogeneous. Fast blue-labelled neurons with
      tyrosine hydroxylase- and enkephalin-like immunoreactivities were found in the
      nucleus locus coeruleus, nucleus subcoeruleus, Kolliker-Fuse nucleus, and the
      medial and lateral parabrachial nuclei. Approximately 87% of tyrosine hydroxylase
      like immunoreactive neurons had enkephalin-like immunoreactivity, whereas about
      76% of the enkephalin-like immunoreactive neurons had tyrosine hydroxylase-like
      immunoreactivity. About 71% of all coerulospinal neurons exhibited both tyrosine
      hydroxylase- and enkephalin-like immunoreactivities. These findings indicate that
      coerulospinal activity may lead to spinal cord effects reflecting both
      norepinephrine and enkephalin activity in most cases but do not rule out each
      transmitter's isolated functions.

PMID- 1351396
TI  - Co-expression of tyrosine hydroxylase messenger RNA 1 and 2 in human ventral
      mesencephalon revealed by digoxigenin- and biotin-labelled
      oligodeoxyribonucleotides.
AB  - In situ hybridization experiments, using oligodeoxyribonucleotides specific for
      the two major expressed human tyrosine hydroxylase mRNAs, were performed on human
      brain sections at the level of the mesencephalon. The specificity of the probes
      was ascertained by Northern blot experiments carried out with independently in
      vitro synthesized human tyrosine hydroxylase mRNAs. For in situ hybridization
      experiments, oligodeoxyribonucleotides were labelled with nucleotides tagged with
      digoxigenin or biotin molecules. The hybridized oligonucleotides were detected by
      antibodies coupled with peroxidase and alkaline phosphatase enzymes, which yield,
      with appropriate substrates, brown and purple products, respectively. The
      simultaneous detection of the two mRNAs with digoxigeninated and biotinylated
      probes revealed that these two mRNAs are co-expressed in single cells. The purple
      product obtained with alkaline phosphatase exhibits a discrete distribution
      within the dopaminergic cells suggesting these mRNAs are associated with sub
      cellular structures. Finally, a heterogeneity in the intensity of the labelling
      of reactive cells with both probes was visualized as well as the expression of
      the two mRNA species in neurites.

PMID- 1351397
TI  - Light microscopic radioautographic localization of somatostatin binding sites in
      the brainstem of the rat.
AB  - The distribution of somatostatin binding sites was investigated by light
      microscopic radioautography in the brainstem of the rat following in vitro
      labeling with 125I-Tyr0-DTrp8-somatostatin14. Moderate to high labeling densities
      were detected within the superior colliculus, the locus coeruleus and
      subcoeruleus, the parabrachial complex, the nucleus of the solitary tract and the
      dorsal motor nucleus of the vagus. Most of the white matter was devoid of
      specific somatostatin binding except for fibers of the glossopharyngeal nerve and
      the spinal trigeminal tract. In most of the labeled areas, 125I-somatostatin
      binding was evenly distributed between neuropil and perikarya. In a few
      instances, however, the binding clearly predominated over nerve cell bodies:
      namely in the dorsal motor nucleus of the vagus and in the pontine and medullary
      tegmentum. In the latter two regions, the labeled neurons were identified in
      adjacent sections by tyrosine hydroxylase immunohistochemistry as belonging to
      the A5 and A1 catecholamine cell groups, respectively. These findings, together
      with the confirmed association of somatostatin binding sites with noradrenergic
      neurons in the locus coeruleus, suggest that interactions with catecholaminergic
      systems may represent a major mode of action for somatostatin in the brainstem.

PMID- 1351398
TI  - [Liver enzyme values (gamma-GT, GOT, GPT) in intoxicated drivers at the time of
      the offense].
AB  - The enzyme activities (GGT, GPT, GOT), especially of the gamma-glutamyl
      transpeptidase, is considered to be a sign of alcohol abuse. Of 219 blood samples
      taken from drunken drivers for blood alcohol determination, 81 (37.6%) exhibited
      pathological enzyme activities. In 55.6% of them specifically pathological gamma
      Gt values were found. In the cases with normal enzyme activities the average
      value of blood alcohol concentration was 1.61%, the pathological cases had 1.81%.
      In the latter cases more than 50% of the drunken drivers involved were workers.
      Most of them were 30-49 years old (45%), but also young drivers up to 21 years
      old were represented (about 25%). There was also a difference between the group
      with normal and pathological enzyme activity concerning their drinking behaviour.
      The group with pathological values occurred during the week, the other group was
      mostly arrested at the weekends. Of the total, 6.8% (15) were women, 4 exhibited
      pathological enzyme activities; three of them were 21-29 years, one was 36 years
      old. The data obtained demonstrate that drunken drivers exhibit a tendency to
      alcohol abuse.

PMID- 1351399
TI  - Domains of cellular retinoic acid-binding protein I (CRABP I) expression in the
      hindbrain and neural crest of the mouse embryo.
AB  - We describe here the distribution of cellular retinoic acid-binding protein I
      (CRABP I) in the head of the early mouse embryo from day 8 to day 13 of
      gestation, using both in situ hybridisation to localise mRNA and
      immunocytochemistry to localise protein. The distribution of mRNA and protein was
      found to be identical. CRABP I first appeared in part of the presumptive
      hindbrain of the presomite embryo and then became localised to rhombomeres 2, 4,
      5 and 6. The only other area of expression in the cephalic neuroepithelium was in
      a part of the midbrain roof. The neural crest and its mesenchymal derivatives,
      the branchial arches, expressed CRABP I and crest could be seen streaming from
      the neuroepithelium of individual rhombomeres into particular branchial arches.
      This suggested a fate map could be constructed describing the rhombomeric origin
      of branchial arch mesenchyme. Later in development, axons throughout the
      hindbrain expressed CRABP I. The results are considered in terms of the role of
      retinoic acid in the specification of neuronal phenotype in the hindbrain and in
      axon outgrowth.

PMID- 1351400
TI  - Cell type dependent transcription regulation by chick homeodomain proteins.
AB  - Five chick homeodomain proteins (CHOXs), CHOX-1.7, -1.1, -1.4, -4.2 and -2.6, had
      different transcription-regulating activities in a chick cultured cell line, LMH.
      In particular, CHOX-1.7 highly activated transcription when NP6 was used as the
      target site whereas CHOX-1.4 did not. This was mainly due to differences in the
      activation domains since both proteins bound to NP with almost the same
      affinities in vitro. In LMH cells, they competitively acted on target gene
      transcription. Moreover, the strength of the CHOX-1.4 activation domain depended
      on the cell type. These findings suggest that the effect on a target gene is
      determined by a combination of CHOXs and cell types.

PMID- 1351401
TI  - The presence of a dehydroepiandrosterone-specific receptor binding complex in
      murine T cells.
AB  - We have investigated the ability of dehydroepiandrosterone (DHEA) to alter the
      production of interleukin-2 (IL-2) and to bind to a specific binding complex in
      antiCD3 epsilon activated T cells. Binding activity correlated with the presence
      of a specific DHEA binding complex in the cytosol and nuclei of DHEA-responsive T
      cell hybridomas, as well as in CD4+ and CD8+ cells isolated from peripheral lymph
      nodes of normal mice. Scatchard analysis determined that intact lymphocytes and
      cytosolic fractions contained high affinity binding for [3H]DHEA (approx. 2.6 nM)
      with 1000-7000 binding sites existing per cell. Five of the T-cell hybridomas
      tested both responded to DHEA treatment with increased production of IL-2 and
      also contained specific high affinity [3H]DHEA binding. Four additional T-cell
      hybridomas were found to contain no specific [3H]DHEA binding and were also
      unresponsive to DHEA influences on IL-2 production. Sucrose density gradients
      demonstrated a 3-4s [3H]DHEA binding complex in high salt and a 7-8s binding
      complex in low salt. Specific binding was inhibited by preincubation of the
      cytosol fractions with either trypsin or chymotrypsin, or by heating to 60
      degrees C for 1 h (less than 15% of control). [3H]DHEA binding was unaffected by
      preincubation of the cytosol fractions with ribonuclease, deoxyribonuclease, or
      phospholipase A. The DHEA-protein complexes bound to DNA-cellulose with the
      amount of binding being slightly increased by preincubation at 25 degrees C as
      compared to 4 degrees C. As expected, [3H]DHEA binding was inhibited by the
      addition of unlabeled DHEA, but was also modestly inhibited by
      dihydrotestosterone and cortisol. Binding of DHEA was unaffected by progesterone,
      dexamethasone, estradiol, androsterone, DHEAS, and beta-etiocholanolone at all
      concentrations tested. DHEA was incapable of inhibiting the binding of [3H]DHT to
      the androgen receptor or [3H]dexamethasone to the glucocorticoid receptor.
      Collectively, these findings suggest that murine T cells contain a specific DHEA
      receptor. We believe that DHEA is a steroid hormone that is directly involved in
      the regulation of IL-2 production by both normal and some T-cell hybridomas.

PMID- 1351402
TI  - Resonance Raman microprobe spectroscopy of rhodopsin mutants: effect of
      substitutions in the third transmembrane helix.
AB  - A microprobe system has been developed that can record Raman spectra from as
      little as 2 microL of solution containing only micrograms of biological pigments.
      The apparatus consists of a liquid nitrogen (l-N2)-cooled cold stage, an epi
      illumination microscope, and a substractive-dispersion, double spectrograph
      coupled to a l-N2-cooled CCD detector. Experiments were performed on native
      bovine rhodopsin, rhodopsin expressed in COS cells, and four rhodopsin mutants:
      Glu134 replaced by Gln (E134Q), Glu122 replaced by Gln (E122Q), and Glu113
      replaced by Gln (E113Q) or Ala (E113A). Resonance Raman spectra of
      photostationary steady-state mixtures of 11-cis-rhodopsin, 9-cis-isorhodopsin,
      and all-trans-bathorhodopsin at 77 K were recorded. The Raman spectra of E134Q
      and the wild-type are the same, indicating that Glu134 is not located near the
      chromophore. Substitution at Glu122 also does not affect the C = NH stretching
      vibration of the chromophore. The fingerprint and Schiff base regions of the
      Raman spectra of the 380-nm, pH 7 forms of E113Q and E113A are characteristic of
      unprotonated retinal Schiff bases. The C = NH modes of the approximately 500-nm,
      pH 5 forms of E113Q and E113A in H2O (D2O) are found at 1648 (1629) and 1645
      (1630) cm-1, respectively. These frequencies indicate that the protonated Schiff
      base interacts more weakly with its protein counterion in the Glu113 mutants than
      it does in the native pigment. Furthermore, perturbations of the unique
      bathorhodopsin hydrogen out-of-plane (HOOP) vibrations in E113Q and E113A
      indicate that the strength of the protein perturbation near C12 is weakened
      compared to that in native bathorhodopsin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351404
TI  - Characterization of putative neurotransmitter N-acetyl-aspartyl-glutamic acid and
      some related compounds by fast atom bombardment and tandem mass spectrometry.
AB  - The characterization of the N-blocked neuropeptide N-acetyl-aspartyl-glutamic
      acid and of some related compounds was carried out by negative-ion fast atom
      bombardment mass spectrometry and collision-induced dissociation of the generated
      [M-H]- species. Thorough analysis of the fragment ion spectra allowed
      discrimination between sequence isomeric compounds, and highlighting of
      differences between dipeptides linked in the normal or iso mode.

PMID- 1351403
TI  - Incorporation of dietary oleate, linoleate, alpha-linolenate and
      eicosapentaenoate into the plasma lipid fractions of four strains of rat.
AB  - Four strains of rat (Dark Agouti, DA; Ginger Hooded, GH; Portion, P; Hooded
      Wistar, HW) were fed elemental diets containing different sources of fat at the
      10% (w/w) level. The dietary fats used included the following oils; olive (rich
      in oleate), sunflower (rich in linoleate), linseed (rich in alpha-linolenate) and
      fish (rich in eicosapentaenoate and docosahexaenoate). Differences between
      strains in response to individual diets were modest compared with the much
      greater differences achieved by the dietary treatments. In general, the changes
      in polyunsaturated fatty acid (PUFA) levels in the plasma lipids of all rat
      strains followed the major PUFA in the diet. There were, however, strong
      interactions between dietary n-6 and n-3 PUFA which affected not only the level
      of particular PUFA in lipid fractions but also the lipid fraction in which a
      particular PUFA appeared. Our findings indicate that a response to dietary fats
      in the plasma lipids of one strain of rat can be expected to occur with
      relatively minor variations in other commonly used rat strains.

PMID- 1351405
TI  - Depressive syndromes in schizophrenic patients under neuroleptic therapy. ANI
      Study Group Berlin, Dusseldorf, Gottingen, Munich, Federal Republic of Germany.
AB  - Schizophrenic outpatients (= 364) were assigned at random to three different
      treatment strategies: (1) continuous medication with neuroleptic drugs, (2)
      intermittent medication with crisis intervention and (3) intermittent medication
      with early intervention. Depressive syndromes were rated according to three
      different scales for depressive syndromes (Brief Psychiatric Rating Scale anxious
      depression factor, Arbeitsgemeinschaft fur Methodik und Dokumentation in der
      Psychiatrie/depression, and the self-rating Paranoid Depression Scale) after 1
      and 2 years of treatment. No differences in depression scores were found between
      the three treatment strategies. Comparisons between patients treated with
      neuroleptic drugs at the time and patients without neuroleptics revealed
      significantly higher depression scores in the neuroleptics group in most
      comparisons. No differences were found between patients treated with low versus
      high potency neuroleptics and between oral versus depot neuroleptics. However,
      depression correlated with extrapyramidal symptoms.

PMID- 1351406
TI  - Electron microscopic observation of Taylorella equigenitalis with pili in vivo.

PMID- 1351407
TI  - The inheritance of type I and type III von Willebrand's disease in Israel:
      linkage analysis, carrier detection and prenatal diagnosis using three intragenic
      restriction fragment length polymorphisms.
AB  - Three intragenic restriction fragment length polymorphisms (RFLPs) were used to
      study linkage and analyse the mode of inheritance in type I and type III von
      Willebrand's disease (vWD). In two families linkage was established between Sac I
      RFLPs and the inheritance of type I vWD. RFLP analysis of amniocyte DNA from a
      potentially affected foetus enabled us to establish a prenatal diagnosis of vWD
      in a third family with type I vWD. Linkage was also established in four families
      between the Sac I and two Taq I RFLPs and the inheritance of type III vWD. All
      type III probands were homozygotes and inherited the same mutant vWF allele from
      both parents. Heterozygous carriers from one type III family were phenotypically
      normal and could be detected only by linkage analysis, whereas carriers from the
      remaining three type III families were asymptomatic but had decreased values of
      vWF antigen and activity. RFLP-based linkage analysis of vWD alleles provides a
      way to improve the diagnostic precision, detect carriers, and may be useful for
      prenatal diagnosis of type III vWD.

PMID- 1351408
TI  - Immunocytochemistry and calcium cytochemistry of the mammalian pineal organ: a
      comparison with retina and submammalian pineal organs.
AB  - Morphologically the mammalian pineal organ is a part of the diencephalon. It
      represents a neural tissue histologically ("pineal nervous tissue") and is
      dissimilar to endocrine glands. Submammalian pinealocytes resemble the
      photoreceptor cells of the retina, and some of their cytologic characteristics
      are preserved in the mammalian pinealocytes together with compounds demonstrable
      by cyto- and immunocytochemistry and participating in photochemical transduction.
      In our opinion, the main trend of today's literature on pineal functions--only
      considering the organ as a common endocrine gland--deviates from this structural
      and histochemical basis. In mammals, similar to the lower vertebrates, the
      pinealocytes have a sensory cilium developed to a different extent. The axonic
      processes of pinealocytes form ribbon-containing synapses on secondary pineal
      neurons, and/or neurohormonal terminals on the basal lamina of the surface of the
      pineal nervous tissue facing the perivascular spaces. Ribbon-containing axo
      dendritic synapses were found in the rat, cat, guinea pig, ferret, and hedgehog.
      In the cat, we found GABA-immunoreactive interneurons, while the secondary nerve
      cells, whose axons enter the habenular commissure, were GABA-immunonegative. GABA
      immunogold-labeled axons run between pinealocytes and form axo-dendritic synapses
      on intrapineal neurons. There is a similarity between the light and electron
      microscopic localization of Ca ions in the mammalian and submammalian pineal
      organs and retina of various vertebrates. Calcium pyroantimonate deposits-
      showing the presence of Ca ions--were found in the outer segments of the pineal
      and retinal photoreceptors of the frog. In the rat and human pineal organ,
      calcium accumulated on the plasmalemma of pinealocytes and intercellularly among
      pinealocytes. The formation of pineal concrements in mammals may be connected to
      the high need for Ca exchange of the pinealocytes for their supposed receptor and
      effector functions.

PMID- 1351409
TI  - Neurobiological aspects of panic disorder.
AB  - The limbic system, temporal cortex and the locus coeruleus are important brain
      regions in the neuroanatomy of panic states. There is evidence for beta- and
      alpha 2-adrenoreceptor abnormalities and pre- and post-synaptic serotonergic
      alterations in panic disorder subjects. The anti-panic effects of chronic
      antidepressant drug treatment may relate to their down-regulation of various
      components of noradrenergic function and overall enhancement of serotonergic
      function. The efficacy of benzodiazepine agents in panic disorder and the altered
      sensitivity of panic patients to benzodiazepine agonists and inverse agonists
      suggest that alterations in benzodiazepine/GABA receptors may have a role in this
      disorder. A variety of other pharmacological agents also provoke panic,
      demonstrating that the biological origins of this disorder are quite diverse and
      complicated. Most importantly, a variety of new agents that selectively affect
      different components of these neurotransmitter/receptor systems are being
      developed. These novel agents offer future promise of greater efficacy with less
      adverse effects for individuals with panic disorder.

PMID- 1351410
TI  - Beta-adrenergic agonists for acute, severe asthma.
AB  - OBJECTIVE: To critically review the use of beta-adrenergic agonists in acute,
      severe asthma with particular focus on aerosol administration. DATA SOURCES:
      English language articles published since 1971 on the use of beta-agonists for
      acute asthma. Studies were identified from bibliographies of book chapters,
      review articles, and other research articles. STUDY SELECTION: All studies (21
      total) comparing systemic with inhaled beta-agonists were reviewed, regardless of
      their design or outcome. Selected studies highlighting specific aspects of beta
      agonist use in acute asthma such as beta-agonists versus other bronchodilators,
      aerosol delivery, and intravenous beta-agonists were also reviewed. DATA
      EXTRACTION: Performed subjectively by the authors with specific aspects of
      quality discussed within the body of the article. DATA SYNTHESIS: The beta
      agonists provide superior bronchodilation in acute severe asthma compared with
      either the methylxanthines and/or anticholinergics. The majority of studies found
      aerosolized beta-agonists to be either as effective as or more effective than
      parenteral beta-agonists and to produce fewer adverse cardiovascular effects.
      Studies showing preference for parenteral therapy have either been of poor design
      or used low doses of an aerosolized beta-agonist. Based on studies of aerosol
      delivery, there is no advantage of jet nebulization over metered-dose inhalers;
      however, other aspects, including ease of administration, favor nebulization as
      the delivery method of choice. The articles recommending intravenous beta
      agonists consist of a series of uncontrolled cases. CONCLUSIONS: Aerosolized
      selective beta 2-agonists are the bronchodilator treatments of choice for acute,
      severe asthma. Attention to the details of dosing and delivery are required for
      optimal results. The final dose and dosing interval are determined by the
      patient's response. Intravenous beta-agonists are hazardous and cannot be
      recommended.

PMID- 1351411
TI  - Metered-dose inhalers and nebulizers in the acute setting.
AB  - OBJECTIVE: This article evaluates the current literature comparing beta
      adrenergic agonists administered via metered-dose inhalers (MDIs) with nebulizer
      devices in adult and pediatric patients. These studies focus on the acute
      treatment of asthma or chronic obstructive pulmonary disease in the emergency
      department and other acute care settings. DATA SOURCES: English-language journal
      articles published between 1980 and 1991. STUDY SELECTION: Eight studies that
      compared beta-adrenergic agonists administered via an MDI or an MDI with a
      spacing device versus a nebulizer were identified. All of the studies were either
      poorly designed or had few subjects. By consensus of the authors, all were
      included in the review. DATA EXTRACTION: Studies were assessed according to
      methodologic strength (e.g., prospective, comparative). DATA SYNTHESIS: Five
      studies found no differences between administration methods, one study found
      metered-dose inhalation to be superior, and another found nebulization to be
      superior based on observed improvements in pulmonary function tests. There were
      no significant differences in adverse-reaction rates. When surveyed, subjects
      preferred MDIs to nebulizers. There were marked variations in doses administered
      within and between studies. There was no consideration given to doses potentially
      delivered to the lungs. CONCLUSIONS: There is no significant difference between
      nebulizers and MDIs plus a spacer with regard to the administration of beta
      agonists in the treatment of acute asthma. There are insufficient data to
      conclusively support the role of spacers in this setting. The choice of a
      specific delivery method at this time must be determined on an individual basis,
      taking into account the issues of cost, timeliness of administration, and
      personnel availability.

PMID- 1351413
TI  - Application of restrained minimization, simulated annealing and molecular
      dynamics simulations for the conformational analysis of oligosaccharides.
AB  - The purpose of the present study was to determine the confidence with which the
      small number of 1H NMR nuclear Overhauser effect (NOE) distance constraints
      measurable across glycosidic linkages in oligosaccharides could be used for
      solution conformational analysis. This was assessed by use of these constraints
      in restrained molecular mechanical minimization of the tetrasaccharide Gal beta 1
      ---4(Fuc alpha 1----3)Glc-NAc beta 1----3Gal, a model compound of the Lewis-X
      antigenic determinant. This presents a particularly severe test case in view of
      extreme resonance overlap and a dearth of inter-residue distance constraints. It
      is concluded that these constraints, when used in conventional restrained
      minimization, result in the generation of 'virtual conformations' and local
      minima about glycosidic linkages. However, these restraints are nevertheless
      found to be useful in the initial stages of a conformational analysis strategy
      involving restrained minimization combined with dynamical simulated annealing to
      define more accurately the global minimum energy configuration, together with
      molecular dynamics simulation to explore conformational mobility about this
      minimum. Theoretical ROE values calculated over the time course of the MD
      simulation, using a formalism appropriate for the time scale of the internal
      motion, are compared with those obtained experimentally in the oligosaccharide.

PMID- 1351414
TI  - [Endoscopy in internal medicine seminar 12. Wiesbaden, 25-26 April 1992].

PMID- 1351415
TI  - Structure and function of neuromuscular junctions in the vastus lateralis of man.
      A motor point biopsy study of two groups of patients.
AB  - The properties of neuromuscular junctions (NMJs) in the vastus lateralis of man
      have been studied in motor point biopsy samples and compared with those reported
      for lower vertebrates (frogs and mice). The patients studied had no convincing
      evidence of a primary disturbance of neuromuscular transmission or other
      neurogenic component. Morphological studies were made using a variety of methods
      at the light- and electron-microscope levels. The size of the presynaptic nerve
      terminal and the area of postsynaptic specialization were smaller, relative to
      the size of the muscle fibres, than in the lower vertebrates. In contrast, the
      extent of postsynaptic folding was greater. Intracellular recordings from single
      muscle fibres showed that the duration of synaptic currents was longer than in
      most other vertebrates so far studied and that the number of transmitter 'quanta'
      released by a single nerve impulse, about 20, was lower, probably reflecting the
      small size of the presynaptic terminals. The hypothesis is discussed that in man,
      a relatively weak effect of transmitter on the muscle fibre surface is amplified
      by voltage-dependent sodium channels which have been shown in the rat to be
      concentrated in the depths of the synaptic folds. The implications of this
      hypothesis for the interpretation of pathological findings in myasthenic
      syndromes are also discussed.

PMID- 1351416
TI  - Adenosine modulation of dynorphin B release by hippocampal synaptosomes.
AB  - A rat hippocampal preparation enriched in mossy fiber synaptosomes was employed
      in an attempt to expose any relationship between endogenous adenosine and the
      release of dynorphin B-like immunoreactivity (DynB-LI). Presumptive blockade of
      purinergic receptors increased the spontaneous release of DynB-LI, and reducing
      synaptic adenosine by exogenous adenosine deaminase increased the K(+)-evoked
      release. Evoked release of DynB-LI was reduced by inhibitors of adenosine uptake
      and 5'-nucleotidase. Taken together, these data suggest that adenosine endogenous
      to hippocampal mossy fiber synaptosomes serves to inhibit the release of one of
      the peptide neuromodulators of this preparation, and provide support for the
      concept of autoregulation of release.

PMID- 1351412
TI  - Ocular beta-blockers in glaucoma management. Clinical pharmacological aspects.
AB  - Topical beta-blockers reduce the intraocular pressure (IOP) by blockade of
      sympathetic nerve endings in the ciliary epithelium causing a fall in aqueous
      humour production. Two types of topical beta-blockers are available for use in
      glaucoma: nonselective, which block both beta 1- and beta 2-adrenoceptors; and
      cardioselective, which block only beta 1-receptors. Of the beta-Blockers
      commercially available, timolol, levobunolol, metipranolol and carteolol are
      nonselective, and betaxolol is cardioselective. Twice-daily timolol is probably
      the most effective agent in lowering IOP, although levobunolol is equally
      effective and can be used once daily with little difference in effect. Carteolol
      is used twice daily and any theoretical advantage in diminished side effects
      conferred by its partial beta-agonist activity compared with timolol has not been
      fully substantiated. Metipranolol is effective twice daily and does not have
      partial beta-agonist activity. Betaxolol has an effect comparable to timolol in
      lowering IOP, but is less effective in some patients. beta-Blockers can be used
      with other antiglaucoma medications, but their combined action with epinephrine
      (adrenaline) is suspect, particularly in the case of the nonselective beta
      blockers, and the effect should be assessed in patients on an individual basis.
      Local stinging can be a problem in some patients with betaxolol. The most serious
      side effects of beta-blockers are the exacerbation of chronic obstructive airways
      disease with nonselective agents and the precipitation of bronchospasm in some
      patients. Betaxolol seems relatively free of adverse respiratory effects,
      although this may be dose-related and extreme caution should still be exercised
      in patients with any history of respiratory illness. Because of the lower risk of
      precipitating side effects, betaxolol is probably the beta-blocker of first
      choice for use in glaucoma; timolol or levobunolol are reserved for patients who
      do not respond satisfactorily to betaxolol and are quite free of respiratory
      disease.

PMID- 1351417
TI  - Role of the deep mesencephalic nucleus in the antinociception induced by
      stimulation of the anterior pretectal nucleus in rats.
AB  - The present study showed that the inhibitory effect on the tail-flick reflex (TF)
      of stimulating the deep mesencephalic nucleus (DpMe) was very similar to that
      produced by stimulation of the anterior pretectal nucleus (APtN). An electrolytic
      lesion of the ipsilateral DpMe greatly reduced the inhibitory effect of APtN
      stimulation on the TF. Furthermore, activating the neuronal cell bodies in DpMe
      but not the fibers of passage by microinjection of L-glutamate into this area was
      also shown to elicit inhibition of TF. On the other hand, inhibiting the neuronal
      cells in DpMe by microinjection of gamma-aminobutyric acid produced a marked
      reduction in the APtN-induced inhibition of TF, which was comparable to that
      produced by DpMe lesions. It is suggested that the APtN-induced antinociception
      is, at least in part, mediated via a relay through the DpMe.

PMID- 1351418
TI  - [Decrease of pineal AMPc and TOH activity in the superior cervical ganglia after
      ablation of submaxillary glands in rats].
AB  - In order to investigate a possible functional relationship between the
      submandibular salivary gland (SSG) and the central nervous system (CNS), we have
      extirpated the salivary organs from thirty male rats. Twenty days after ablation
      both the pineal glands and the cervical superior ganglions (CSG) were dissected,
      homogenized and frozen until AMPc and TOH were assayed respectively. We observed
      a significant decrease in pineal AMPc (53.9 +/- 6.2 vs 76.1 +/- 7.6% of maximum
      value; p less than 0.02) which seems to be linked with a significant drop in TOH
      activity measured at CSG level (1.5 +/- 0.6 vs 3.7 +/- 0.9 nmoles of DOPA/h/pair
      GCS; p less than 0.03). Our results suggest that both findings might be due to
      the lack of NGF normally reaching the CSG from SSG. This data reinforces the idea
      of a functional link between SSG and CNS via the pineal gland.

PMID- 1351419
TI  - Gn-RH analogues in obstetrics and gynaecology: focus on leuprorelin acetate.
      Proceedings of a symposium. Stockholm, Sweden, October 12, 1991.

PMID- 1351420
TI  - Progression of Takayasu's aortitis in a young Japanese woman: serial angiographic
      study.
AB  - Progression of Takayasu's aortitis was observed by serial angiography over 2
      years. Acute aortic regurgitation due to marked dilatation of the proximal
      ascending aorta was followed by aneurysmal dilatation of the distal ascending
      aorta. Aneurysmal dilatation of the carotid arteries then developed, with
      subsequent obstruction of both the bilateral vessels by thrombosis.

PMID- 1351421
TI  - A cytoplasmic chaperonin that catalyzes beta-actin folding.
AB  - We have isolated a cytoplasmic chaperonin based on its ability to catalyze the
      folding of denatured beta-actin. The cytoplasmic chaperonin is organized as a
      multisubunit toroid and requires Mg2+ and ATP for activity. The folding reaction
      proceeds via the rapid ATP-independent formation of a binary complex, followed by
      a slower ATP-dependent release of the native product. Electron microscopic
      observations reveal a striking structural change that occurs upon addition of
      Mg2+ and ATP. The eukaryotic cytoplasm thus contains a chaperonin that is
      functionally analagous to its prokaryotic, mitochondrial, and chloroplastic
      counterparts.

PMID- 1351422
TI  - Inhibitory effect of taxol, a microtubule stabilizing agent, on induction of DNA
      synthesis is dependent upon cell lines and growth factors.
AB  - Growth-arrested rat fibroblasts, 3Y1, and human diploid fibroblasts, TIG-1, were
      induced to synthesize DNA by stimulation with various agents such as fetal bovine
      serum (FBS), epidermal growth factor (EGF), colcemid, or colchicine. Taxol, a
      microtubule-stabilizing agent, blocked the induction of DNA synthesis after
      stimulation with colcemid or colchicine in both cell lines. Taxol inhibited the
      induction of DNA synthesis after stimulation with FBS or EGF in TIG-1, but did
      not in 3Y1. 12-O-tetradecanoylphorbol-13-acetate (TPA) induced DNA synthesis in
      TIG-1, which was reduced only partly by taxol. Taxol stabilized or polymerized
      microtubules in both cell lines. These results indicate that the inhibitory
      effect of taxol on the induction of DNA synthesis varied among cell lines and
      among growth factors, and suggest that signal transduction processes may be
      differentiated by taxol sensitivity. In TIG-1 cells, when taxol was added within
      6 h, about halfway into the initiation of DNA synthesis after the addition of FBS
      or EGF, the inhibition of DNA synthesis still occurred. Taxol did not inhibit the
      induction of c-fos and c-myc genes by FBS or EGF stimulation. Colchicine itself
      did not induce these genes in TIG-1. Thus, taxol appeared to inhibit the
      induction of DNA synthesis not by blockage in the early transduction process of
      the growth signal from the cell surface to nuclei but by blockage in processes
      operating in the mid- or late-prereplicative phase.

PMID- 1351423
TI  - Study on stereospecificity of enzyme reaction related to peroxisomal bile acid
      synthesis in rat liver.
AB  - We examined stereoselectivities of enzymes related to bile acid formation in
      hepatic peroxisomes using two stereoisomers of 3 alpha,7 alpha,12 alpha
      trihydroxy-5 beta-cholestanoic acid (THCA) and its coenzyme A (CoA) derivatives.
      The activity of acyl-CoA synthetase for 25 S-THCA was 1.4-times higher than that
      for 25 R-THCA. The difference was also observed after clofibrate-treatment. This
      activity was located in microsomes, differing from palmitoyl-CoA synthetase
      located in mitochondria, peroxisomes and microsomes. There was no
      stereoselectivity in the reaction of peroxisomal fatty acyl-CoA oxidase for THCA
      isomers, and the activity was one tenth of that for acyl-CoA synthetase.
      Considering the overall reaction of peroxisomal bile acid formation, the
      stereoselective difference observed in THCA-CoA synthesis should be denied. Thus,
      the previous finding that the overall formation of bile acid from THCA was not
      stereoselective was further confirmed. Furthermore, the activity for THCA
      oxidation was not induced by clofibric acid, suggesting that there would be
      different isozymes of peroxisomal acyl-CoA oxidase against THCA-CoA and palmitoyl
      CoA.

PMID- 1351424
TI  - Autoradiographic characterization of beta-adrenergic receptor subtype in the
      canine conduction system.
AB  - It has been hypothesized, based on physiological evidence, that there is a
      greater proportion of beta 2-adrenergic receptors on the myocytes of the
      conduction system when compared with the working myocardium. The purpose of these
      studies was to examine beta-adrenergic receptor subtype in the conduction system
      of the dog by using the technique of coverslip autoradiography. Scintillation
      studies of [125I]pindolol binding to ventricular sections demonstrated that
      binding was saturable (dissociation constant of 116 pM), had the correct order of
      potency for a beta-receptor, and was stereoselective. Both betaxolol (beta 1
      selective) and ICI-118,551 (beta 2-selective) competition curves fit a two-site
      model in nonlinear curve-fitting analyses (78% beta 1-receptors).
      Autoradiographic studies determined that the myocytes of the sinoatrial node had
      approximately twice as many autoradiographic grains as the surrounding atrial
      myocytes. The myocytes of the atrioventricular bundle had a number of grains
      similar to the number in surrounding septal myocytes. Autoradiographic inhibition
      curves with betaxolol or ICI-118,551 demonstrated that both the sinoatrial node
      and the atrioventricular bundle had inhibition profiles similar to the
      surrounding myocytes (predominantly beta 1) but unlike the inhibition profiles of
      arterioles (predominantly beta 2). Calculations using the dissociation constants
      derived from the nonlinear curve-fitting analysis and the percent specific
      binding in the presence of 4 x 10(-7) M betaxolol or ICI-118,551 determined that
      the proportion of beta 1- to beta 2-receptors was the same (70-80% beta 1) when
      comparing the sinoatrial node and the surrounding atrial myocytes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1351425
TI  - Role of neutrophil adherence receptors (CD 18) in lung permeability following
      lower torso ischemia.
AB  - Ischemia and reperfusion of the lower torso lead to leukotriene- and neutrophil
      (PMN)-dependent lung injury characterized by lung PMN sequestration, increased
      permeability, and noncardiogenic edema. It is thought that PMNs require adhesion
      to endothelium to alter barrier function. This study tests the role of CD 18, the
      PMN adherence receptor, in mediating lung permeability after lower torso ischemia
      and reperfusion. Anesthetized rabbits (n = 9) underwent 3 hours of bilateral hind
      limb ischemia. Ten minutes after the release of the tourniquets, plasma
      leukotriene B4 levels increased to 395 +/- 85 pg/ml, higher than 129 +/- 35 pg/ml
      in controls (n = 9, p less than 0.01). At this time there was a reduction in
      circulating white blood cells (x 10(3)), 3.56 +/- 0.49/mm3 relative to 6.07 +/-
      0.61/mm3 in controls (p less than 0.01). PMNs were sequestered in the hind limbs,
      indicated by increased myeloperoxidase activity of 1.06 +/- 0.19 units/g compared
      with 0.56 +/- 0.09 units/g in controls (p less than 0.05). Four hours after
      tourniquet release, PMNs were sequestered in the lungs, 52 +/- 4 PMNs per 10 high
      power fields, a value higher than 31.5 +/- 3 PMNs per 10 high-power fields in
      controls; bronchoalveolar lavage fluid protein content increased to 554 +/- 90
      micrograms/ml relative to 277 +/- 46 micrograms/ml in controls; and there was
      lung edema, measured by increased wet weight-to-dry weight ratios of 5.19 +/-
      0.10, higher than 4.29 +/- 0.21 in controls (all p less than 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1351426
TI  - Postnatal changes in AMPA receptor regulation by phospholipase A2 treatment of
      synaptic membranes: temporally differential effects on agonist and antagonist
      binding.
AB  - Previous results have indicated that phospholipase A2 (PLA2) treatment of
      telencephalic membranes produced opposite effects on [3H]amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) binding in neonatal and adult rats. In
      the present study, we compared the effects of PLA2 treatment of telencephalic
      membranes on the binding characteristics of agonists and antagonists of the AMPA
      receptors in the developing rat brain. Whereas PLA2 treatment of telencephalic
      membranes from postnatal day (PND) 5 and 10 animals produced an important
      decrease in [3H]AMPA binding, the same treatment performed on PND 20, 25 and
      adult membranes resulted in a marked increase in [3H]AMPA binding; the shift from
      decreased to increased [3H]AMPA binding occurred at about PND 15. In contrast to
      [3H]AMPA binding, [3H]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) binding was
      substantially reduced following PLA2 treatment at PND 5, 10 and 20, and effect
      due to a decrease in the maximal number of [3H]CNQX binding sites. In adult
      membranes, the effect of PLA2 treatment on [3H]CNQX binding was markedly reduced
      when compared to neonatal membranes. Pretreatment of synaptic membranes with
      PCMBS (a sulfhydryl reagent) increased [3H]AMPA binding in both young (PND 10)
      and adult telencephalic membranes, without significantly changing [3H]CNQX
      binding. The various effects of PLA2 treatment on agonist and antagonist binding
      did not appear to be due to major differences in the pharmacological properties
      of the AMPA receptors at different ages. The present results indicate that the
      characteristics of the binding sites for agonists and antagonists of the AMPA
      receptors are differentially modulated by the lipid environment during the
      postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351427
TI  - Ontogenesis of pyroglutamyl peptidase II activity in rat brain, adenohypophysis
      and pancreas.
AB  - Pyroglutamyl peptidase II (PPII; E.C. 3.4.19.-) is a highly specific membrane
      bound ectoenzyme degrading thyrotropin releasing hormone (TRH). The ontogenesis
      of this enzyme was measured in rat brain regions, adenohypophysis and pancreas.
      In hypothalamus PPII activity was maximal at day 8 postnatal, decreasing to adult
      values at day 45. The postnatal ontogenic patterns in posterior cerebral cortex
      and hypothalamus were similar. In olfactory bulb, two peaks of activity were
      observed (3th and 22nd day) while in adenohypophysis it appeared only at day 8,
      increased to day 30, decreasing thereafter to adult values.

PMID- 1351428
TI  - Increased tyrosine hydroxylase immunoreactivity in the rat cortex following
      prenatal cocaine exposure.
AB  - Cocaine has been found to be a neurobehavioral teratogen in both animals and
      humans. In this study the effects of cocaine on the developing catecholamine
      systems were examined. Rats were treated gestationally with cocaine (40 mg/kg
      s.c.) or saline from gestational day 13 until parturition. On postnatal day 28,
      tyrosine hydroxylase immunocytochemistry was performed. Increases in
      catecholamine fiber densities were observed in the hippocampus, anterior
      cingulate cortex, and parietal cortex in cocaine-treated animals. These findings
      may explain some of the behavioral alterations seen following prenatal cocaine
      exposure.

PMID- 1351429
TI  - Polymorphisms at the GLUT2 (beta-cell/liver) glucose transporter gene and non
      insulin-dependent diabetes mellitus (NIDDM): analysis in affected pedigree
      members.
AB  - The precise genetic defects underlying the etiology of non-insulin-dependent
      diabetes mellitus (NIDDM) have yet to be identified. The beta-cell/liver glucose
      transporter gene GLUT2 represents a good candidate for the etiology of the
      disease, being involved in the glucose signalling for beta-cell insulin release.
      Population association studies of the GLUT2 gene in NIDDM have so far yielded
      controversial results. In order to determine the possible contribution of this
      gene to the inheritance of NIDDM, we have employed a new approach, where two
      polymorphic markers of the GLUT2 locus, detected with the restriction enzyme Taq
      1, were examined for linkage with the disease in a group of 22 Italian pedigrees
      with affected members (n = 50). Departure from independent segregation between
      markers and disease was analyzed by the Affected-Pedigree-Members (APM)
      statistical method. Furthermore, association analysis between the Taq-1 RFLPs at
      the GLUT2 locus and NIDDM was performed in a group of diabetics with a strong
      family history, comprising the 22 probands and 23 other diabetics with an
      affected first-degree relative. The results indicate that there was no
      segregation distortion between the Taq-1 markers of the GLUT2 gene and the
      disease in the pedigrees examined. Also, no significant difference in genotype
      distribution, haplotype and allele frequencies was found between diabetics and
      controls for the two Taq-1 RFLPs. We conclude that genetic variation at the GLUT2
      transporter gene is unlikely to contribute in a major way to the inheritance for
      NIDDM in this Italian population.

PMID- 1351430
TI  - Deletions, duplications and novel restriction fragment length polymorphism in
      Duchenne and Becker muscular dystrophies.
AB  - To determine the mutations of Southern Chinese with Duchenne and Becker muscular
      dystrophies (DMD, BMD), we analysed 28 DMD and BMD patients in 24 unrelated
      families for intragenic deletions and duplications by using cDNA probes covering
      the entire 14 kb of the dystrophin gene. Deletions were detected in nine
      unrelated patients (seven patients by probe 8 and two by probe 2b-3). Gene
      duplications were detected by probe 1-2a in two patients with the duplication
      bands confirmed in both Hind III and Bgl II digests and by densitometry. A third
      patient was found to have a junction fragment with Bgl II and a duplication band
      with Hind III by probe 5b-7. Therefore 50% of the 24 unrelated families were
      found to have either deletions or duplications. A previously undescribed
      restriction fragment length polymorphism (RFLP) was found in one family with
      probe 5b-7 in Bgl II digests which was found to segregate with the disease
      phenotype. This new RFLP was not detected in over 70 unrelated X chromosomes we
      have examined so far, and appeared to be "private" for this family. The presence
      of this new restriction site may or may not be the mutation responsible for the
      disease phenotype.

PMID- 1351431
TI  - Impaired proliferative capacity and abnormal cytokine profile of naive and memory
      CD4 T cells from HIV-seropositive patients.
AB  - Purified naive and memory CD4 T cells from healthy donors, HIV+ asymptomatic
      carriers and AIDS patients were examined for their proliferative activity and
      their pattern of cytokine secretion (IL-4, IL-6, interferon-gamma (IFN-gamma) and
      tumour necrosis factor-alpha (TNF-alpha)) upon stimulation with
      phytohaemagglutinin (PHA), phorbol myristate acetate (PMA) and cross-linked anti
      CD3 MoAb, in the presence of recombinant IL-2 (rIL-2). We found a decrease in the
      proliferative capacity of naive CD4 T cells following stimulation with PHA and
      PMA, and a sharp decline in this response upon cross-linked anti-CD3 stimulation
      in both subsets, although it predominated in the naive subpopulation. In AIDS
      patients, less pronounced impairment of thymidine uptake by the naive subset was
      found upon PHA and cross-linked anti-CD3 MoAb stimulation. In addition, an
      altered secretion pattern of the different cytokines was observed, consisting of
      abnormal secretion of IL-6 by both naive and memory cells, an abnormal pattern of
      IFN-gamma secretion and frequent loss of detectable IL-4 production by HIV
      patients. These abnormalities were even more pronounced in AIDS patients than in
      the asymptomatic carriers. Overall, our results extend previous reports
      indicating functional impairment of memory CD4 subsets in HIV+ subjects by
      showing that this impairment involves naive CD4 T cells.

PMID- 1351432
TI  - Tumour necrosis factor-dependent parasite-killing effects during paroxysms in non
      immune Plasmodium vivax malaria patients.
AB  - Plasmodium vivax malaria infections in non-immune individuals manifest as
      periodic clinical episodes of fever with chills and rigors known as paroxysms. We
      have demonstrated that in non-immune patients the period of paroxysm is
      associated with the transient presence of plasma factors which kill gametocytes,
      the intra-erythrocytic sexual stages of the malaria parasite which transmit the
      infection from humans to mosquito, rendering them non-infectious to mosquitoes.
      Gametocyte killing in paroxysm plasma is mediated by tumour necrosis factor (TNF)
      acting in conjunction with other essential serum factor(s). Plasma TNF levels
      were elevated during a paroxysm. In semi-immune individuals from a P. vivax
      endemic area clinical symptoms of malaria are mild and the parasite killing
      factors are not induced during paroxysm. Serum TNF levels were correspondingly
      lower in endemic patients during a paroxysm. Human peripheral blood mononuclear
      cells (PBMC) can be stimulated in vitro by extracts of P. vivax blood stage
      parasites to produce TNF and associated parasite killing factor(s), thus
      simulating in vitro the events that occur during a paroxysm, this being the
      release of parasite exo-antigens by rupturing schizonts and the subsequent
      induction of PBMC to produce TNF and other parasite-killing factors. We were able
      to show that convalescent serum from P. vivax semi-immune individuals block the
      induction of TNF and parasite-killing factors by malaria antigens in vitro,
      presumably through antibodies that neutralize parasite exo-antigens. Thus,
      individuals living in malaria-endemic areas appear to acquire clinical immunity
      to malaria by avoiding their induction during infection; we have shown that one
      such mechanism is the neutralization of parasite exo-antigens that induce the
      production of parasite killing factors.

PMID- 1351434
TI  - Antineutrophil cytoplasmic antibody (cANCA and pANCA) titers in relation to
      disease activity in patients with necrotizing vasculitis: a longitudinal study.
AB  - The significance of the antineutrophil cytoplasmic antibodies, cANCA or pANCA, in
      relation to disease activity in various types of necrotizing vasculitis was
      assessed in a longitudinal study. Twenty patients, 14 cANCA positive and 6 pANCA
      positive were followed for up to seven years. Eleven of the 14 cANCA positive and
      two out of the 6 pANCA positive patients had Wegener's granulomatosis, two other
      cANCA patient and one pANCA patient had systemic vasculitis, whereas one cANCA
      and three pANCA positive patients had disease limited to the kidneys. Disease
      activity was expressed as a numerical index DAI, based on extent and type of
      organ involvement (DAI greater than or equal to 5 = active disease). At the time
      of disease debut the DAI ranged between 11 and 32, cANCA titers between 18 and
      greater than 1000 U/l, and pANCA titers between 51 and 630 U/l in individual
      patients. With clinical recovery both c- and pANCA titers declined. Clinical
      remission (DAI less than 5) occurred within a mean of 2.5 months (range 1 to 4).
      Almost simultaneously cANCA titers turned negative (less than 10 U/l), although
      one patient remained positive for seven years. pANCA titers remained positive for
      long periods of time in 5/6 patients. Five cANCA patients had clinical
      exacerbations, which in two patients were preceded by seroconversions from - to
      +, lasting 3 and 12 months before the clinical relapse. One additional cANCA
      patient had two serological relapses without signs of clinical activity during a
      2-year follow-up. In conclusion, we saw a close correlation between DAI and cANCA
      titers in individual patients: with decreasing clinical activity (DAI), the cANCA
      titers decrease. Interindividual variation is great; despite a high DAI, the
      cANCA titers may be relatively low. Serological relapses may indicate forthcoming
      clinical relapses. Relapses may develop as late as 5-6 years after onset. pANCA
      titers, on the other hand, tend to remain positive for long periods, despite
      clinical remission.

PMID- 1351435
TI  - Case report: therapeutic bronchial artery embolization in a case of Takayasu's
      arteritis.
AB  - The pulmonary arteries are frequently involved in Takayasu's arteritis with a
      reported incidence of 41-100% in affected individuals. Patients are usually
      asymptomatic, however, often despite extensive pulmonary involvement. We describe
      a patient with Takayasu's arteritis who presented with haemoptysis caused by
      bronchial artery hypertrophy secondary to occlusive pulmonary arterial disease,
      who was treated by bronchial artery embolization. This is, to our knowledge, the
      first reported case of haemoptysis secondary to Takayasu's arteritis successfully
      treated by embolization.

PMID- 1351436
TI  - The pivotal role of the plasma membrane-cytoskeletal complex and of epithelium
      formation in differentiation in animals.
AB  - 1. If a few exceptions are disregarded, the several somatic cell types of a
      differentiated organism all have an identical genome. They all differ in their
      plasma membrane-cytoskeletal complex. 2. Differences in plasma membrane
      properties usually result in differences in ionic concentrations/activities in
      the cytoplasm and nucleoplasm. A basic question therefore is whether there exists
      a causal relationship between the ionic environment of the nucleus and
      differential gene expression/protein synthesis. 3. Development is switched on by
      a "Ca2+ explosion", often accompanied by pH changes and plasma membrane
      depolarisation. The penetration of the spermatozoon in the plasma membrane acts
      as a trigger. 4. All animal species develop from a blastula. At this stage they
      organise themselves as an epithelium enclosing an inner (fluid) compartment. This
      suggests that epithelium formation is absolutely essential in animal development.
      5. As development proceeds, more and more compartments, lined by different
      epithelia, are formed. Differentiated organisms largely consist of folded
      epithelia. Some cells leave their original epithelial environment and become free
      floating (e.g. blood cells) or engage in other types of organisation. 6.
      Epithelial cells have the ability to segregate some membrane proteins, e.g.
      receptors, ion pumps, ion channels etc., so as to make selective transcellular
      transport possible. The cytoskeleton plays an important role in this segregation
      and in the interconnection of epithelial cells. 7. Transembryonic electric
      currents which have been measured by the vibrating probe technique, are due to
      electrogenic ion transport by epithelia. 8. Segregation of membrane proteins is
      not an exclusive property of epithelial cells but it is probably a property of
      all animal cell types, single cells inclusive; asymmetry is the rule, symmetry-
      if it exists at all--the exception. 9. Differences in several plasma membrane
      proteins (receptors, ion transporting molecules, cell adhesion molecules and
      signal transducing systems) are not only causally related to differential
      transcellular transport but also indirectly to differential protein synthesis and
      hence to differentiation. There are already a few well documented examples of
      "electrical" control of gene expression. 10. The major "strategy" which applies
      in differentiation seems to be to keep the genome constant but to change over and
      over its ionic and macromolecular environment, both acting in a complementary
      way. The first one may be considered as the coarse tuning mechanism of gene
      expression-protein synthesis, the second as the fine one. In our opinion this
      might be a principle universal to differentiation processes in all animal
      species.

PMID- 1351433
TI  - CD4+ T cells clear virus but augment disease in mice infected with respiratory
      syncytial virus. Comparison with the effects of CD8+ T cells.
AB  - Respiratory syncytial (RS) virus-specific T cell lines were derived from the
      spleens of BALB/c mice primed by intranasal infection with RS virus. The lines
      were expanded by repeated antigenic stimulation in vitro, and separated into CD4+
      and CD8+ T cell-enriched fractions by immunomagnetic adhesion. The effects of
      passive transfer of these fractions into RS virus infected mice were observed.
      The most severe immunopathological changes were seen in mice receiving CD4+
      cells. Transfer of CD4+, CD8+ or both cell fractions caused RS virus-infected
      mice to become ill and lose weight. Both cell lines caused an increase in the
      severity of lung pathology (as monitored by bronchoalveolar lavage) with the
      appearance of lung haemorrhage and polymorphonuclear cell efflux. In addition,
      recipients of CD4+ cells developed striking pulmonary eosinophilia. In CD4+ cell
      recipients, 5 x 10(5) cells were sufficient to decrease lung virus titre, whereas
      2 x 10(6) CD8+ cells were needed to produce a similar effect. The unseparated T
      cell line and the CD4+ cell fraction secreted significant amounts of IL-3, IL-4
      and IL-5 (P less than 0.001). High levels of IL-2 were produced only by the
      unseparated T cell line. The CD8+ cell fraction secreted IL-3 only. The results
      show that, cell-for-cell, CD4+ cells are more anti-viral and more
      immunopathogenic than CD8+ cells in RS virus infected mice. Such effects may have
      contributed to the augmented disease seen in some infants vaccinated against RS
      virus.

PMID- 1351437
TI  - The effects of surfactants on the permeability of isolated perfused fish gills to
      urea.
AB  - 1. The diffusional transfer capacity of [14C]urea in isolated perfused trout
      (Oncorhynchus mykiss) gills in the presence of sodium n-dodecylsulphate (SDS), n
      dodecyltrimethylammonium bromide (DTAB) and p-t-octylbenzene oxyethylene10
      (Triton X-100) has been measured over a range of surfactant concentrations. 2.
      Urea has been shown to be transported transcellularly through the respiratory
      cells of the gill secondary lamellae by passive diffusion. Each surfactant was
      found to markedly increase the rate of diffusion and the diffusional transfer
      capacity reached a steady-state at a particular surfactant concentration. 3. The
      steady state flux was increased by surfactant in the sequence DTAB greater than
      SDS greater than Triton X-100 and the surfactant concentrations in terms of the
      critical micelle concentration (CMC) at which the diffusional transfer capacities
      reached limiting values were 0.92 x CMC (SDS), 0.53 x CMC (DTAB) and 2.5 x CMC
      (Triton X-100). 4. Compared to interactions between isolated epithelial cells and
      the surfactants, the rates at which the surfactants changed the urea flux were
      slow, suggesting that the mucus layer plays a significant role in protecting the
      epithelial cells of the secondary lamellae from disruption. 5. Relative to the
      other surfactants, DTAB had the most marked effect on both the rate of flux
      change and on the magnitude of the change, at concentrations which are low
      relative to the CMC, suggesting a more specific interaction with the negatively
      charged mucus layer consistent with the toxic effects of quaternary ammonium
      compounds on aquatic organisms.

PMID- 1351438
TI  - Effects of somatostatin on inositol-1,4,5-trisphosphate content in mouse spleen
      lymphocytes.
AB  - 1. The effects of somatostatin-14 (SS) and diazepam in vitro on the content of
      inositol-1,4,5-trisphosphate (IP3) in mouse spleen lymphocytes were investigated.
      2. It was found that the exposure of mouse spleen lymphocytes in vitro to SS
      sharply diminished their IP3 level. 3. Diazepam had no effect on lymphocytes IP3
      content. 4. The inhibition of phosphatydyloinositol (PI) breakdown was suggested
      as one of the mechanisms of the physiological SS action.

PMID- 1351439
TI  - Interaction between cortisol and cortisol-binding protein in silver foxes (Vulpes
      fulvus).
AB  - 1. Selection of silver foxes for domestic behaviour resulted in the parallel
      lowering of both cortisol and cortisol-binding protein (CBP) levels in the blood
      plasma. 2. During seasonal cycles (summer-winter) and after stress an increase in
      cortisol levels is followed by a decrease in CBP activity. 3. It is concluded
      that there are two types of interaction between cortisol and CBP in silver foxes:
      parallel changes in the process of domestication and opposite changes under the
      influence of environmental factors.

PMID- 1351440
TI  - Effect of antiserum to rat adipocytes on growth and body composition of the rat.
AB  - 1. Antibody against intact adipocytes was produced in sheep and was capable of
      binding to intact rat adipocytes using an immunofluorescent assay. An antibody
      dose level was established and subsequently used in vivo. 2. This study
      demonstrated inconsistent response of passive immunization procedures with crude
      antibody against rat adipocytes. Establishment of specific protocols for each
      antibody preparation would be essential for using this immunological approach in
      body fat reduction.

PMID- 1351441
TI  - Antigenic cross-reactions among immunoglobulin of diverse vertebrates
      (elasmobranchs to man) detected using xenoantisera.
AB  - 1. Antisera raised in rabbits and goats against intact immunoglobulins or their
      constituent light and heavy chains from man, mouse and the galapagos shark
      (Carcharhinus galapagenesis) were tested for their reactivity with
      immunoglobulins of elasmobranchs, other lower vertebrates and eutherian and
      prototherian mammals. 2. Xenoantisera directed against human heavy chain isotypes
      allowed the serological identification of IgM and IgG immunoglobulins in the
      echidna (Tachyglossus aculeatus), a monotreme which is one of the most primitive
      species of extant mammals. 3. The antisera to heavy chains reacted to varying
      degrees with purified immunoglobulins of non-mammalian species, including the
      chicken, teleost fish and elasmobranchs in a fashion that was specific for
      immunoglobulins, but was not related to defined human isotypic markers. 4. The
      reactions of some antisera seem to skip species known to possess homologous
      immunoglobulins. 5. Antisera directed against isotypic markers of human kappa and
      lambda light chains reacted with shark light chains in a manner that was specific
      for light chain determinants but was not isotype-related. 6. Antisera directed
      against heavy chains of either sharks or mammals reacted with heavy chains, but
      not with light chains of diverse species. 7. A rabbit antiserum specific for
      shark light chain reacted with human and murine monoclonal lambda chains and with
      two synthetic peptides corresponding to human V lambda Fr3 and Fr4 sequences. 8.
      These results establish that a variety of antigenic markers including
      conformational and linear determinants can be shared among immunoglobulins of
      vertebrates species that had an ancestral divergence more than 400 million years
      ago.

PMID- 1351442
TI  - Stimulation of hepatic thyroxine 5'-deiodinase activity in rainbow trout
      (Oncorhynchus mykiss) by Pacific salmon growth hormone.
AB  - 1. Growth hormone extracted from Pacific salmon pituitaries (sGH) was injected
      intra-peritoneally into rainbow trout to determine sGH effects on plasma levels
      of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and properties of the hepatic 5'
      deiodinase enzyme (5'-D) responsible for T4 to T3 conversion. 2. After 24 hr, sGH
      (0.1 or 0.5 microgram/g) did not alter the plasma T4 level or 5'-D, Km, but
      elevated plasma T3 and especially 5'-D Vmax. 3. Thus sGH, like the previously
      tested human GH, acutely enhances the potential for extra-thyroidal T3 production
      in trout by increasing the functional level of hepatic 5'-D, but without changing
      the plasma T4 level.

PMID- 1351443
TI  - Heat exchange by the pinna of the African elephant (Loxodonta africana).
AB  - 1. Surface temperatures of the pinnae of four female African elephants were
      measured at ambient temperatures between 14 and 32 degrees C using infrared
      thermography. Instantaneous heat losses calculated using those values ranged from
      10.67 to 76.2 W under the observed conditions. 2. Using a value of 17
      kcal/kg/day, those heat losses account for 0.65-4.64% of the animals' standard
      metabolic rates, considering one side of one ear only. 3. A model of heat flow
      across a flat vertical plate was constructed and compared to the actual values.
      Up to 100% of an African elephant's heat loss needs can be met by movement of its
      pinnae and by vasodilation. 4. Thermography indicates that the temperature
      distribution pattern across the pinna changes with ambient temperature and that
      areas of specialized motor control exist.

PMID- 1351444
TI  - Elements of acid-base balance in the European bison, Bison bonasus (L.) in the
      winter period.
AB  - 1. In the blood of 65 European bison divided into four groups (Group 1, 0-3-year
      old males; Group 2, 0-3-year-old females; Group 3, mature bulls, over 3 years
      old; Group 4, mature cows, over 3 years old) the values of pH, pCO2, pO2, base
      excess and bicarbonate level were studied. 2. The studies were carried out in
      winter months, from mid-December to mid-April. 3. No significant differences in
      parameters studied were found between young males and females. 4. All indices
      found in mature bulls and cows showed significant differences between all other
      groups. 5. Most of parameters examined here in European bison are comparable with
      those found in other big ruminants.

PMID- 1351445
TI  - Metabolic rate and evaporative water loss at different ambient temperatures in
      two species of fox: the red fox (Vulpes vulpes) and the Arctic fox (Alopex
      lagopus).
AB  - 1. Resting metabolic rate (RMR) and evaporative water loss (EWL) of adult red and
      arctic foxes were determined over ambient temperature (Ta) ranges of -13-37
      degrees C and -5-30 degrees C as oxygen consumption and amount of water in
      expired air using an open flow system. 2. The average RMR was 2.60 +/- 0.14 W/kg
      for the winter red fox, 2.59 +/- 0.14 W/kg for the summer red fox, and 2.35 +/-
      0.11 W/kg for the winter arctic fox. 3. The rate of increase of RMR was
      significant (P less than 0.05) only for Ta range above 27 degrees C. The slopes
      for this Ta range were 0.152 for the winter red fox, and 0.283 for the winter
      arctic fox. 4. The upper critical temperature (Tuc) of the red fox is probably
      between 30 and 32 degrees C. The Tuc of the arctic fox is probably between 26 and
      28 degrees C. The lower critical temperatures (Tlc) were not reached. 5. A strong
      linear relationship between the EWL and Ta was found for Ta range above 27
      degrees C. The slopes for this Ta range were 0.523 for the winter red fox, and
      1.025 for the winter arctic fox. 6. Probably, there are neither significant
      intraspecific seasonal nor interspecific differences in the RMR and EWL. The two
      species seem to differ only in their critical temperatures.

PMID- 1351446
TI  - Effects of arginine vasotocin, cortisol and adrenergic factors on water balance
      in the toad Bufo bufo: physiology or pharmacology?
AB  - 1. The threshold level of exogenous arginine vasotocin (AVT) for increasing the
      cutaneous water permeability in Bufo bufo was several times higher than has been
      measured in dehydrated frogs and toads. 2. The beta-agonist isoproterenol was
      without effect on water balance in hydrated toads but increased the response to
      large doses of AVT by 25-50%. 3. Implantation of cortisol pellets in water
      acclimated toads enhanced the cutaneous water permeability by a factor of 2-3. 4.
      It is concluded that understanding of water balance in terrestrial anurans may
      depend upon the unravelling of mechanisms that integrate cutaneous water
      transport and diuresis.

PMID- 1351447
TI  - Hypoxia-induced changes in electrophysiological responses and associated calcium
      movements of flounder (Platichthys flesus) heart and gut.
AB  - 1. Flounder hearts subjected to hypoxic conditions showed a reduction in
      contractile force. After 85 min in hypoxia-inducing salines, hearts were almost
      totally quiescent. 2. Membrane potentials were seen to change in hearts during
      hypoxic conditions. The action potential gradually declined in height but
      increased in duration and the resting membrane potential was also seen to
      decrease. 3. Sections of flounder gut, when subjected to identical hypoxic
      conditions as the hearts, showed no significant changes in either mechanical
      activity or membrane potential. 4. Heart and gut tissues were placed in hypoxia
      inducing salines containing 45Ca either immediately or after a previous 3 hr
      exposure to hypoxia-inducing salines. Uptake of 45Ca increased beyond control
      values in both heart and gut subjected immediately to hypoxia. After 3 hr hypoxia
      exposure, uptake of 45Ca was reduced in heart but was not significantly different
      from controls in gut. 5. The changes seen in 45Ca uptake were far greater in
      heart tissue than in gut tissue. 6. In all physiological parameters examined, the
      gut tissue of the flounder is far more tolerant to hypoxic conditions than heart
      tissue.

PMID- 1351448
TI  - The effects of hypoxic stress on the fine structure of the flounder heart
      (Platichthys flesus).
AB  - 1. Flounder hearts were examined by conventional transmission electron
      microscopy. Hearts showed clear evidence of a coronary circulation but no
      intrinsic conduction network or innervation was detected. 2. The box-like cells
      showed many surface inpocketings and many scattered glycogen granules and
      membrane bound liposomes. The nucleus position was variable and the cells
      contained numerous small ovoid mitochondria. 3. Dark staining intercalated discs
      with clear nexal and desmosomal areas separated individual cells. 4. No organized
      T-tubular system or sarcoplasmic reticulum was present but the cells displayed
      abundant surface vesicles which may perform the physiological role of the latter.
      5. Hearts of flounder subjected to 3 weeks hypoxia showed striking changes to the
      mitochondria which were smaller than in controls and there was evidence of
      increased mitochondrial budding and also evidence of mitochondrial necrosis. 6.
      Hypoxically-stressed hearts exhibited normal liposome populations but increased
      glycogen granule deposits. These hearts also showed evidence of myofibril
      degeneration with torn Z discs and with a build up of fibrous material. 7. It is
      concluded that the cellular damage seen in hypoxic cells may be due to excessive
      calcium accumulation or increased catecholamine release.

PMID- 1351449
TI  - Influence of blood sample collection on the haematocrit value of two teleosts:
      rainbow trout (Oncorhynchus mykiss) and European sea bass (Dicentrarchus labrax
      L.).
AB  - 1. The effects of the volume of blood extracted, number of extractions, and
      weight upon the haematocrit value of a freshwater teleost (Oncorhynchus mykiss)
      and a marine one (Dicentrarchus labrax) have been studied. 2. For trout with the
      same weight, the increase in the volume of blood extracted results in a
      significant increase in the haematocrit value. 3. For the same volume of blood
      extracted--in trout of the same weight--the second extraction results in a
      significant increase in the haematocrit value. 4. In sea bass, haematocrit
      variations in relation to the aforementioned parameters are not produced. 5. For
      both species there is a positive and significant correlation between weight (W)
      and haematocrit value (Ht), which coincides with the Ht = aWb model, in the range
      of weights used in this study.

PMID- 1351450
TI  - Skeletal muscle capillarization and fiber types in urban and homing pigeons
      (Columba livia).
AB  - 1. Fiber types, capillary supply and other morphometrical parameters were
      analysed in pectoral, gastrocnemius and pronator muscles of homing and urban
      pigeons. 2. The two kinds of birds were analysed before and after a restrainment
      period of at least 5 months. 3. Only slight differences in fiber type frequencies
      were noted between urban and homing pigeons in control conditions. 4. The effect
      of restrainment on the different parameters studied was unclear in gastrocnemius
      and pronator muscles and negligible in M. pectoralis. 5. Mean diffusion distances
      for oxygen from capillaries were smaller in oxidative fibers; also,
      vascularization indexes were higher for these fiber types. 6. The contribution of
      each fiber type to total sectional ara of muscle remains stable in spite of fiber
      type frequencies heterogeneity.

PMID- 1351452
TI  - Effects of hypoxia on renal function in carp, Cyprinus carpio.
AB  - 1. Changes in urine and blood properties and heart rate (HR) of carp were
      investigated during and following hypoxia. 2. When carp were exposed to hypoxic
      conditions, urine flow in some carp increased immediately. However, it decreased
      gradually with time. Osmotic pressure and Na+, Cl-, Ca2+ and Mg2+ levels in urine
      increased in contrast to urine flow. K+, P, ammonium, and lactic acid levels in
      urine increased gradually. 3. When carp lost their balance, blood pH and plasma
      K+ were lower, and RBC, Ht, Hb, Mg2+, P, ammonium, lactic acid, and glucose in
      plasma were higher than those of the control. 4. As water-dissolved oxygen level
      was restored, urine flow increased immediately and soon decreased to the control
      rate. Other urine properties showed higher values than the initial levels and
      decreased with time. No significant change was found in urinary protein. 5. The
      relationship between HR and urine flow is discussed.

PMID- 1351451
TI  - Characterization of the transport of tri- and dicarboxylates by pig intestinal
      brush-border membrane vesicles.
AB  - 1. Transport of citrate and fumarate across the pig intestinal brush-border
      membrane (BBM) was investigated using isolated BBM vesicles. 2. Citrate and
      fumarate uptake was stimulated by an inwardly directed Na+ gradient consistent
      with Na+/citrate (fumarate) co-transport. Cis-inhibition and trans-stimulation
      experiments strongly suggest the existence of a common transport site for tri-
      and dicarboxylates. 3. The protonated forms of citrate (citrate-1, citrate-2)
      seem to be much better transported than citrate-3, indicated by the strong
      stimulation of citrate uptake at an extravesicular pH of 5.6 compared to pH 7.8.
      4. Uptake of tri- and dicarboxylates seems to be potential-sensitive since
      citrate and in particular fumarate transport was enhanced by an inside negative
      potential difference. 5. Kinetics of succinate transport revealed a single
      carrier-mediated component with apparent kinetic constants of 0.43 nmol/mg
      protein-3 s (Vmax) and 0.14 mmol/l (Km).

PMID- 1351453
TI  - Distribution of 125I-endothelin-1,-2,-3 binding sites in mammalian kidneys.
AB  - 1. Binding sites for 125I-labeled endothelin (ET) isopeptides ET-1, ET-2 and ET-3
      were visualized by autoradiography in the kidneys of man, baboon, rhesus monkey,
      tree shrew, pig and rat. 2. Highest levels of binding for the three isoforms were
      observed in the glomeruli, cortical and medullary vessels of baboon, rhesus
      monkey, pig and rat, whereas there was no noticeable labeling of glomeruli in
      human and tree shrew kidneys. 3. The enrichment of binding sites depended on the
      species and peptide investigated, suggesting different affinities and/or
      densities of a heterogenous population of renal ET receptors.

PMID- 1351454
TI  - A comparison of methods of measuring chromatic activity in the integument of a
      teleost.
AB  - 1. Pallor induced by noradrenalin (5 x 10(-7) mol/kg) injection of dark
      Pseudopleuronectes americanus was measured as increase in skin reflectance and
      the degree of melanosome aggregation determined. 2. Mean skin reflectance
      increased approximately 30% on the Munsell neutral value scale. 3. At maximal
      mean reflectance, melanosomes were fully aggregated in most epidermal
      melanophores, but displayed more variable aggregation in dermal melanophores. 4.
      Individual reflectance estimates did not provide consistent indications of
      melanosome aggregation at maximum pallor. 5. The relative merits of reflectance
      and cellular methods of estimating melanophore activity are discussed with
      particular reference to this species.

PMID- 1351455
TI  - Hematologic and blood chemistry data for the prairie dog (Cynomys ludovicianus).
AB  - 1. The prairie dog has been used extensively for the study of gallstone genesis
      and gallstone dissolution therapies, and has recently been implicated in an
      effort to prevent total parenteral nutrition-associated cholelithiasis with
      intravenous chenodeoxycholate. 2. Towards this effort, it is important that a
      range of normal blood chemistry values be reported for the prairie dog. This
      paper reports the mean values for a complete blood cell count, electrolytes,
      blood urea nitrogen, creatinine, calcium, phosphorus, liver enzymes, total
      bilirubin, protein, albumin, cholesterol, triglycerides and lipids for 45 adult
      prairie dogs. 3. The prairie dog has normochromic, microcytic blood with an
      increased number of red blood cells. The prairie dog also has a high
      concentration of small platelets. 4. The prairie dog has a higher CO2
      concentration with a slightly increased potassium concentration than is found in
      man. The anion gap is 12 with a calculated serum osmolality of 316. The BUN
      concentration is elevated with a 3-fold increase in the AST concentration. 5. The
      prairie dog has lower serum values for cholesterol, VLDL and LDL cholesterol than
      man. In the prairie dog, HDL cholesterol consists of 67% of the total cholesterol
      concentration and the LDL and HDL ratio is 0.3.

PMID- 1351456
TI  - The vasopressor action of angiotensin in the snake Bothrops jararaca.
AB  - 1. Carotid blood pressure from anesthetized B. jararaca snakes was recorded in
      order to study angiotensin action in this reptile. 2. Whereas [Asn1,Val5] AII and
      AIII were less potent than [Asp1,Ile5] AII and [Asp1,Val5] AII, [Sar1,Ile5] AII
      was slightly more potent. 3. Captopril abolished the responses to AI (0.01-3
      micrograms/kg). 4. [Sar1,Ala8] AII was uneffective but [Sar1,Leu8] AII or
      phenoxybenzamine were able to reduce AII vasopressor responses. 5. These results
      led to the conclusion that the vasopressor response of AII in B. jararaca is due
      to an interaction with its own receptor but, part of the AII receptor population
      seems to be coupled to the sympatho-adrenal system. Moreover, structural
      requirements seem to be necessary for the AII response in B. jararaca.

PMID- 1351457
TI  - Effects of salt acclimation on water and urea permeabilities across the frog
      bladder: relationship with intramembrane particle aggregates.
AB  - 1. In salt-acclimated frogs, water and urea bladder permeabilities are markedly
      higher than in tap water-acclimated animals. 2. Intra-membrane particle
      aggregates (IMPA) cover an unusually large surface area of the salt-acclimated
      frog bladder apical plasma membrane. 3. In saline-adapted animals, proteins
      extracted from the apical plasma membrane contain additional species of 19, 26,
      31 and 53-61 kDa. These proteins might be related to the water channels contained
      by IMPA.

PMID- 1351458
TI  - Relationships between calbindin (Mr 28,000) and calcium transport by the eggshell
      gland.
AB  - 1. Eggshell density (mg/cm2) and eggshell gland calbindin decreased in the aged
      hens. 2. Aged hens which laid eggs with a low shell weight and shell density had
      significantly lower intestinal and eggshell gland calbindin as compared with
      those which laid eggs with a high shell weight and shell density. 3. Significant
      correlations were found in aged hens between duodenal or eggshell calbindin and
      shell weight or shell density. 4. The results suggest that: (a) aged hens forming
      light shells absorbed calcium with a lower efficiency than those forming heavy
      shells or than young hens; (b) the decline in shell density in the aged hens is
      caused by a physiological calcium deficiency or by a defect in the hens' ability
      to alter calbindin synthesis in response to calcium needs; (c) in the aged hens,
      the deposition of calcium into the eggshell is dependent on, or at least
      associated with, eggshell gland calbindin.

PMID- 1351460
TI  - The effects of dietary deprivation on body temperature and oxygen consumption in
      black-tailed prairie dogs (Cynomys ludovicianus).
AB  - 1. Body temperature (Tb) and oxygen consumption (VO2) were compared between fed
      (Control), food and water deprived (FWD), and water deprived (WD) black-tailed
      prairie dogs, in the month of January. 2. Mean Tb of Control black-tailed prairie
      dogs (36.2 degrees C) was significantly different from FWD (33.4 degrees C) and
      WD (30.4 degrees C) black-tailed prairie dogs. 3. VO2 was not significantly
      different between FWD and Control black-tailed prairie dogs (4.4 and 4.0 ml
      O2/kg/hr, respectively), while VO2 was significantly different between WD and
      Control animals (2.9 and 4.0 ml O2/kg/hr, respectively). 4. These findings are
      discussed as possible mechanisms for conserving body water.

PMID- 1351459
TI  - Effects of injections of L-alanine, L-glucose and L-ascorbic acid in newly
      hatched turkey poults on glucose metabolism.
AB  - 1. Effects of subcutaneous injections of either L-glucose, L-alanine or L
      ascorbate into newly-hatched, fasted turkey poults were examined. 2. There were
      no effects of injections on blood glucose concentrations at 20 hr post-injection.
      3. Glucose injections inhibited hepatic glucose-6-phosphatase activity while
      alanine injections did not. 4. Both glucose and alanine injections enhanced
      hepatic glycogen reserves at 20 hr post-injection.

PMID- 1351461
TI  - Bile pigments in gallbladder and freshly-secreted hepatic duct bile from fed and
      fasted rainbow trout, Oncorhynchus mykiss.
AB  - 1. Chromatographic analyses of bile pigments in rainbow trout reveal the presence
      of primarily unconjugated biliverdin (BV) and bilirubin (BR) glycosyl conjugates.
      Only trace amounts of unconjugated BR are present in hepatic duct (HD) bile: no
      beta-glucuronidase activity is detectable. 2. The per cent of BV and BR in HD and
      gallbladder biles is similar in fasted trout; however, the per cent of BV is
      significantly increased in HD bile from fed fish. 3. Fasting decreases the rate
      of choleresis but does not alter the excretory rate of endogenous BV or BR. 4.
      Erythrocyte life span is estimated to be approximately 500 days.

PMID- 1351462
TI  - Stimulation of corticosterone secretion by dietary histidine in rats.
AB  - 1. Liver glycogen accumulated within 3 days after the initiation of a histidine
      excess diet. Serum corticosterone increased and serum insulin decreased, but
      plasma glucagon remained unchanged. 2. When 2 mmol (310 mg) of histidine was
      administered to fasted rats, serum corticosterone increased after 5 hr and tended
      to be higher 9 hr after administration. 3. Liver glycogen tended to accumulate
      after 5 hr and had accumulated significantly after 9 hr.

PMID- 1351463
TI  - Digesta retention and fibre digestion in maras (Dolichotis patagonum) and guinea
      pigs.
AB  - 1. Digestibilities of feed and turnover time (1/k), transit time (TT) and mean
      retention time (MRT: 1/k+TT) of fluid and particle markers were measured in maras
      (Dolichotis patagonum) and guinea-pigs (Cavia procellus) fed a diet containing
      50% alfalfa. 2. The digestibility of fibre was similar in both animals, however,
      the digestibilities of crude protein (nitrogen x 6.25) and crude ash were lower
      in the mara than in the guinea-pig. 3. 1/k of the digesta markers were similar in
      both animals, suggesting that the two animals possess similar dilution and
      retention time of digesta in their caecum and proximal colon.

PMID- 1351464
TI  - Lipolytic and diabetogenic effects of native and biosynthetic growth hormone in
      the chicken: a re-evaluation.
AB  - 1. There is controversy as to whether growth hormone (GH) is lipolytic and/or
      diabetogenic in vivo in chickens. The ability of GH to influence circulating
      concentrations of free fatty acids was examined in anaesthetized (suppressing
      endogenous GH secretion) adult and young chickens using three preparations of GH.
      2. Plasma concentrations of free fatty acids were increased following the
      intravenous injection of native bovine GH (50 micrograms/kg to either young or
      adult chickens), recombinant chicken GH (American Cyanamid) (50 micrograms/kg to
      adult chickens) and recombinant chicken GH (Amgen) (50 micrograms/kg to young
      chickens). 3. Similarly, infusion of recombinant chicken GH was accompanied by a
      gradual increase (P less than 0.05, 90 min following start of infusion) in plasma
      concentrations of free fatty acids in both anaesthetized hypophysectomized and
      sham operated young chickens. 4. These data support an acute lipolytic role for
      GH in the chicken. 5. The injection of neither bovine nor chicken GH had any
      consistent effect on circulating concentrations of glucose. Moreover, if GH was
      administered in the presence of glucose, GH had no effect on plasma
      concentrations of glucose. 6. Further evidence for a lack of a diabetogenic role
      for GH comes from the inability of chronic administration of GH to influence the
      decline in plasma concentrations of glucose following challenge with the insulin
      secretagogue, tolabutamide.

PMID- 1351465
TI  - A case of Graves' disease and papillary thyroid carcinoma with predominant
      production of thyroid-stimulation-blocking antibodies (TSBAb) persisted after
      total thyroidectomy.
AB  - A 42-year-old female with Graves' disease and papillary thyroid carcinoma with
      lung metastasis was referred to our hospital. After treatment of thyrotoxicosis
      with methimazole and Lugol's solution, she underwent total thyroidectomy. She was
      then given 131I twice to treat lung metastasis. However, 131I uptake into the
      lung was not clear in the scintigram. Both thyroid-stimulating antibodies (TSAb)
      and thyroid-stimulation-blocking antibodies (TSBAb) were detected in her sera
      before and after the treatments. Compared with TSAb activities, TSBAb activities
      were extremely high. Changes in the titers of these two antibodies were not clear
      after total thyroidectomy. These results indicate that lymphocytes outside the
      thyroid gland are the major source of TSAb and TSBAb in this patient.

PMID- 1351466
TI  - A kindred of multiple endocrine neoplasia type 2B.
AB  - We describe familial cases of multiple endocrine neoplasia (MEN) 2B: A 48-year
      old man is the proband. He had pheochromocytoma, medullary thyroid carcinomas
      (MTCs), parathyroid hyperplasia, mucosal neuromas, eversion of eyelids and
      Marfanoid appearance, and then underwent adrenalectomy and total thyroidectomy.
      Family screening revealed that his two daughters (10 and 8 years old) had mucosal
      neuromas and increased serum calcitonin (CT). Both of them had MTCs but no
      pheochromocytoma, and their MTCs were surgically removed. The father and his
      children have been in favorable condition since the operations. Southern blot
      analysis with 33 polymorphic DNA probes was done in MTCs obtained from two
      daughters. An RBP3 (10q11.2) locus linked to a predisposing gene on chromosome 10
      was uninformative in either patient because of constitutional homozygosity. Loss
      of heterozygosity at the MYCL1 locus on chromosome 1p32 was observed in MTC from
      the younger sister, but no loss of heterozygosity was recognized in other loci
      examined. Deletion of the 1p32 locus may play a role in the development of MEN
      2B.

PMID- 1351467
TI  - The interactions of ethanol with single and repeated doses of suriclone and
      diazepam on physiological and psychomotor functions in normal subjects.
AB  - The effects of diazepam (5 mg t.i.d.), suriclone (0.2 and 0.4 mg t.i.d.) and
      placebo (t.i.d.) were assessed in 12 normal, healthy volunteer subjects after a
      single dose and after treatment for a period of 8 days. A battery of
      physiological, psychomotor and subjective tests was administered on days 1 and 8
      both before and after drug and after a measured dose of ethanol. The effects of
      diazepam on the EEG were characteristic of benzodiazepines-a decrease in the slow
      frequency wave-bands, an increase in fast frequency wave-band and diminished
      evoked response amplitude. Suriclone had similar effects on fast frequency
      activity and evoked response amplitude but, in contrast to diazepam, also
      increased the slow frequency wave-bands after 7 days treatment. Some improvements
      in performance were seen with suriclone on critical flicker fusion, tapping
      speed, spiral maze and digit cancellation. In contrast, suriclone impaired
      performance to a greater extent than diazepam on digit symbol substitution and
      symbol copying. Body sway was also enhanced by suriclone to a greater extent than
      diazepam. Subjective ratings for mood and adverse-effects showed few differences
      between suriclone or diazepam. However, suriclone caused greater gastro
      intestinal disturbances than diazepam, especially after ethanol, and subjects
      rated themselves as more antagonistic and more irritable on suriclone. Ratings
      for calmness suggested that in contrast to diazepam, suriclone had no anxiolytic
      effect. Several of the parameters tested showed a build up of effect with
      diazepam over the treatment period which was not seen with suriclone. It is
      suggested that this difference may be due to differences in elimination
      rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351468
TI  - Use of benzodiazepines and industrial injuries. Service Medical Interentreprises
      de Toulouse, France.
AB  - A one-year case-control study was performed by occupational physicians in 328
      injures people and 662 controls in order to investigate a possible relationship
      between the consumption of benzodiazepines and the occurrence of industrial
      injuries. Benzodiazepine consumption was found to be related to sex (females) and
      age but not to a higher frequency of industrial injuries. It is suggested that
      knowledge of being at risk might be a factor reducing the consumption of
      benzodiazepines.

PMID- 1351470
TI  - Neuroleptic malignant syndrome: description of two cases with prolonged clinical
      course.
AB  - Two cases of neuroleptic malignant syndrome presenting an unusual clinical course
      are reported. The first patient was untreated for the syndrome and recovered
      completely only after four months, while the other one was given dopaminergic and
      myorelaxing drugs only 10 days after the onset of the symptoms and died about six
      months later with an unmodified clinical picture. In both cases the treatment
      seemed to influence the clinical course, a delay or lack of drug intake worsening
      the prognosis.

PMID- 1351469
TI  - The effects of the normal and oncogenic forms of the neu tyrosine kinase, and the
      corresponding forms of an immunoglobulin E receptor/neu tyrosine kinase fusion
      protein, on Xenopus oocyte maturation.
AB  - In this work, we have used Xenopus oocyte maturation as a read-out for examining
      the ability of the neu tyrosine kinase (p185neu) to participate with the
      epidermal growth factor (EGF) receptor in a common signal transduction pathway.
      We find that unlike the case for the EGF receptor, which elicits EGF-dependent
      maturation of these oocytes as reflected by their germinal vesicle breakdown
      (GVBD), neither the normal neu tyrosine kinase (p185val664) nor the oncogenic
      form of neu (p185glu664) are able to effectively trigger this maturation event.
      However, expression of p185glu664 causes a specific and significant promotion of
      the progesterone-induced GVBD, reducing the half-time for this maturation even
      from approximately 9 h to approximately 5 h. Stimulation of the progesterone
      induced GVBD did not occur following the expression of a kinase-deficient p185neu
      protein (in which a lysine residue at position 758 was changed to alanine).
      Essentially identical results were obtained when the mRNAs coding for fusion
      proteins comprised of the extracellular domain of the receptor for immunoglobulin
      E (IgE), and the membrane-spanning and tyrosine kinase domains of normal or
      oncogenic p185neu (designated IgER/p185val664 and IgER/p185glu664, respectively),
      were injected into oocytes. Antigen-induced crosslinking of IgER/p185val164
      proteins expressed in oocytes caused a reduction in the half-time for the
      progesterone-stimulated GVBD from approximately 9 h to approximately 7 h. Thus,
      the aggregation of the membrane-spanning and/or tyrosine kinase domains of
      p185val664 partially mimics the effects of the oncogenic forms of p185neu.
      Overall, the results of these studies suggest that the activation of the p185neu
      tyrosine kinase by a point mutation within its membrane-spanning helix, or an
      aggregation event, can result in the facilitation of oocyte maturation events
      that are elicited by other factors (e.g. progesterone). However, the activated
      p185neu tyrosine kinases are not able to mimic the EGF-stimulated EGF receptor
      tyrosine kinase in triggering oocyte maturation, which suggests that the EGF
      receptor and the p185neu tyrosine kinase do not input into identical signal
      transduction pathways in these cells.

PMID- 1351471
TI  - [Therapeutic consequences of the circadian rhythm. Which measures against early
      morning myocardial ischemia?].

PMID- 1351472
TI  - Effects of quinpirole on autonomic nervous control of heart rate in rats.
AB  - The effects of quinpirole, a specific dopamine DA2 receptor agonist, on autonomic
      nervous control of heart rate, were studied in normotensive pithed rats, by
      analysing its action on the tachycardia and bradycardia evoked by electrical
      stimulation of the cardioaccelerator (10 V; 1 ms; 0.5, 1, 3, 6 Hz) and vagus (10
      V; 1 ms; 3, 6, 9 Hz) nerves respectively. Quinpirole (10-50-100 micrograms kg-1
      iv) reduced the cardioacceleration elicited by electrical stimulation but not
      that by noradrenaline (3 micrograms kg-1 iv). The effect on electrical
      stimulation was blocked by domperidone (0.5 mg kg-1 iv) but not by SCH 23390 (0.2
      mg kg-1 iv) or idazoxan (0.3 mg kg-1 iv). At 1, 5, 10, 30 micrograms kg-1 iv,
      quinpirole decreased vagal but not acetylcholine-induced bradycardia. The effect
      on electrical stimulation was inhibited by domperidone (0.5 mg kg-1 iv) but not
      by SCH 23390 (0.2 mg kg-1 iv), prazosin (0.1 mg kg-1 iv) or idazoxan (0.3 mg kg-1
      iv). The data point to the presence of presynaptic and/or ganglionic dopamine
      receptors in the sympathetic and parasympathetic innervation of the rat heart,
      where stimulation inhibits the release of neuromediators.

PMID- 1351473
TI  - Expression of proliferating cell nuclear antigen in lung cancer: a systematic
      study and correlation with DNA ploidy.
AB  - Heterogeneity of expression of the proliferating cell nuclear antigen (PCNA) was
      assessed immunohistochemically in 156 tissue samples from 33 surgically resected
      pulmonary carcinomas using the monoclonal antibody 19A2. The DNA content of each
      of these samples was measured by flow cytometry. Mean PCNA expression was higher
      in squamous carcinomas than in adenocarcinomas but there was marked intra-tumour
      variation in PCNA index in almost all cases. Intra-tumour heterogeneity of DNA
      content was noted in 11 cases. The PCNA index of these cases (34.1) was higher
      than that of DNA homogeneous cases (19.4). The wide variation in PCNA expression
      between different samples within a tumour would indicate that systematic sampling
      and counting will be necessary in future immunohistochemical studies of cell
      proliferation in tumour material.

PMID- 1351474
TI  - American Indian prehistory as written in the mitochondrial DNA: a review.
AB  - Native Americans have been divided into three linguistic groups: the reasonably
      well-defined Eskaleut and Nadene of northern North America and the highly
      heterogeneous Amerind of North, Central, and South America. The heterogeneity of
      the Amerinds has been proposed to be the result of either multiple independent
      migrations or a single ancient migration with extensive in situ radiation. To
      investigate the origin and interrelationship of the American Indians, we examined
      the mitochondrial DNA (mtDNA) variation in 87 Amerinds (Pima, Maya, and Ticuna of
      North, Central, and South America, respectively), 80 Nadene (Dogrib and Tlingit
      of northwest North America and Navajo of the southwest North America), and 153
      Asians from 7 diverse populations. American Indian mtDNAs were found to be
      directly descended from five founding Asian mtDNAs and to cluster into four
      lineages, each characterized by a different rare Asian mtDNA marker. Lineage A is
      defined by a HaeIII site gain at np 663, lineage B by a 9-bp deletion between the
      COII and tRNA(Lys) genes, lineage C by a HincII site loss at np 13259, and
      lineage D by an AluI site loss at np 5176. The North, Central, and South America
      Amerinds were found to harbor all four lineages, demonstrating that the Amerinds
      originated from a common ancestral genetic stock. The genetic variation of three
      of the four Amerind lineages (A, C, and D) was similar with a mean value of
      0.084%, whereas the sequence variation in the fourth lineage (B) was much lower,
      raising the possibility of an independent arrival. By contrast, the Nadene mtDNAs
      were predominantly from lineage A, with 27% of them having a Nadene-specific RsaI
      site loss at np 16329. The accumulated Nadene variation was only 0.021%. These
      results demonstrate that the Amerind mtDNAs arose from one or maybe two Asian
      migrations that were distinct from the migration of the Nadene and that the
      Amerind populations are about four times older than the Nadene.

PMID- 1351475
TI  - Herpetic stromal keratitis: an immunopathologic disease mediated by CD4+ T
      lymphocytes.
AB  - To investigate the role of T cell subsets in the development of herpetic stromal
      keratitis (HSK) in a well defined model, we used an adoptive transfer approach in
      which thymectomized and T cell-depleted mice [T(-)] were reconstituted with
      different numbers of syngeneic immune T lymphocytes after topical corneal
      challenge with RE strain of herpes simplex virus-1. In vitro stimulated or
      unstimulated immune T cells obtained from cervical and retropharyngeal lymph
      nodes of mice with HSK were used in adoptive transfer experiments. Although T(-)
      mice developed an initial epithelial inflammation, stromal keratitis did not
      occur. Reconstitution experiments revealed that mice that received 2 x 10(7) or
      more unfractionated immune T cells could develop HSK lesions with severity
      comparable to immuno-competent control mice. In mice receiving CD8(+)-depleted
      populations, even fewer cells (5 x 10(6)/mouse) were able to induce significant
      HSK. In contrast, mice that received similar or increased numbers of cells
      depleted of CD4+ T lymphocytes did not develop HSK. Immune T lymphocytes
      transferred to mice that were mock infected on the cornea did not develop HSK,
      indicating that the immunopathogenic cells were virus specific and not merely
      reacting to autoantigens. Histopathologic examination of the diseased corneas
      demonstrated that the stromal inflammation in euthymic normal and T(-)
      reconstituted mice was characterized by extensive polymorphonuclear leukocyte
      infiltration. Scattered lymphocytes, and occasional macrophages also were
      observed. These results provide further evidence that HSK represents an
      immunopathologic process mediated mainly by CD4+ T cells.

PMID- 1351476
TI  - Corneal epithelial glycoproteins exhibit Pseudomonas aeruginosa pilus binding
      activity.
AB  - Adherence of Pseudomonas aeruginosa to the cornea is a requisite step in the
      pathogenesis of bacteria-induced corneal disease. P. aeruginosa is capable of
      attaching to host epithelial cells by its pili, but there is little information
      regarding the epithelial receptors of this adhesin in the cornea. Using nitro
      cellulose blotting of polyacrylamide gels of solubilized adult mouse corneal
      epithelium, four major proteins (molecular weights: 38, 42, 57, and 66 kD) and
      several minor proteins were identified that bound purified pili from strain PAK
      and its hyperpiliated mutant PAK/PR1. These proteins were identified by
      immunoblotting either with pilus-specific monoclonal antibodies, XLR-3 and PK 3B,
      or using peptide PAK 128-144 (OX). The glycosylated nature of the proteins was
      determined using similar gel electrophoresis of corneal epithelial proteins,
      blotting onto nitrocellulose, and staining the blots with lectins conjugated to
      either horseradish peroxidase or alkaline phosphatase. All four major pilus
      binding proteins were stained with concanavalin A lectin (mannose and glucose)
      and either wheat germ agglutinin lectin (WGA, specific for sialic acid and N
      acetylglucosamine) or succinylated WGA lectin (only N-acetylglucosamine).
      Staining for peanut agglutinin lectin (galactose beta(1-3) N-acetylgalactosamine)
      was seen for the 42-, 57-, and 66-kD proteins. The importance of the carbohydrate
      portions of these corneal proteins in pili binding was confirmed by preincubation
      of corneal epithelial blots with periodate or pili with sialic acid, both of
      which abolished the pili binding. These studies indicate that corneal epithelial
      pilus-binding proteins are glycoproteins in nature and that sialic acid may be a
      constituent of these pilus-specific receptors in the adult mouse corneal
      epithelium.

PMID- 1351477
TI  - Re-examination of peripheral blood T cell subsets in dysthyroid orbitopathy.
AB  - Patients with dysthyroid orbitopathy (DO) were grouped according to a
      multifactorial assessment of disease severity and the rate of disease
      progression. Using this system and flow cytometric measurements of T cell subsets
      in the peripheral blood, a significant increase in the percentage of CD4+
      lymphocytes correlated with disease severity in DO patients with progressive
      disease. These observations are consistent with the hypothesis that the CD4+
      peripheral blood T helper cells play a significant role in the progression of DO.

PMID- 1351479
TI  - Cryptorchidism and monorchism in cats: 25 cases (1980-1989).
AB  - Of 1,345 cats admitted for orchiectomy during a 10-year period, 23 (1.7%) were
      cryptorchid and 2 (0.1%) were monorchid. Persian cats were over-represented in
      the cryptorchid population (P = 0.01). Cats were more likely to be unilaterally
      than bilaterally cryptorchid (P = 0.01). A predisposition for location of
      undescended testes (abdominal vs inguinal or right vs left side) was not
      identified in unilateral cryptorchids. All bilateral cryptorchids had abdominally
      located testes. The most common surgical approaches used for orchiectomy of
      cryptorchid cats were a caudal ventral midline incision for inguinal testes and a
      caudal ventral midline celiotomy for abdominal testes.

PMID- 1351478
TI  - Cobalamin deficiency associated with methylmalonic acidemia in a cat.
AB  - A 9-month-old sexually intact male longhair cat was examined because of lethargy,
      anorexia, cold intolerance, and failure to thrive since acquisition at an early
      age. Clinical signs of disease were less pronounced when the cat was fed a low
      protein diet. Anemia, hypoglycemia, low total CO2 content, and hyperammonemia
      were detected. The cat was euthanatized. Urine obtained immediately before
      euthanasia contained a large amount of methylmalonic acid. Total serum cobalamin
      concentration was low. Hepatic methylmalonic-CoA mutase activity, with and
      without the addition of coenzyme adenosylcobalamin, was consistent with a
      cobalamin deficiency. Methylmalonic acidemia secondary to a putative defect in
      cobalamin absorption was diagnosed.

PMID- 1351480
TI  - Novel restriction fragment length polymorphisms in the cellular oncogene SEA.
AB  - The human homologue of the SEA oncogene has been mapped recently to chromosome
      band 11q13. While studying the possible involvement of this gene in the variant
      translocation t(9;22;11) (q34;q11;q13) in a case of chronic myelogenous leukemia,
      we identified novel polymorphisms for XbaI and SacI restriction enzyme sites in
      the SEA gene. Frequency of the polymorphic alleles was studied in 100 samples
      from healthy controls, 94 samples from patients with non-Hodgkin's lymphoma, 25
      samples from patients with benign lymphadenopathy, and 38 samples from patients
      with chronic myelogenous leukemia. XbaI digestion showed a three-allele
      polymorphism with two frequent alleles A (8.0 kb) and B (9.2 kb) and a rare
      allele (5.8 kb). After SacI digestion the probe identified two primary genotypes.
      Genotype I showed two hybridizable DNA fragments, one each of 6.6 and 3.5 kb. In
      genotype II the 3.5 kb fragment was absent, instead two smaller fragments, one
      each of 1.9 kb and 1.6 kb were present. The 6.6 kb fragment (allele AA) had three
      polymorphic sites generating 6.2 kb fragment (allele BB), 7.4 kb fragment (allele
      CC), and 7.8 kb fragment (allele DD). Frequencies of the two genotypes and the
      four alleles followed Mendelian proportions in all the samples studied.
      Furthermore, this study shows the importance of restriction map analysis of DNA
      in the vicinity of the probe of an oncogene to distinguish natural polymorphisms
      from the disease-related rearrangements in the gene.

PMID- 1351481
TI  - Diagnostic confusion in treatment-refractory psychotic patients.
AB  - BACKGROUND: Two surveys of diagnostic practices in the United States suggest that
      many clinicians base their diagnoses on presenting symptoms and pay little
      attention to course and exclusionary criteria. Failure to correctly diagnose
      patients may result in inappropriate therapy and poor treatment response. The
      purpose of the present study was to investigate diagnostic practices. METHODS: We
      made detailed assessments of 50 consecutively admitted treatment-refractory
      psychotic patients and carefully applied DSM-III-R criteria. RESULTS: Referral
      diagnoses were changed in 23 of the 50 patients. Diagnoses of schizophrenia and
      schizoaffective disorder were made far less frequently and mood disorders
      (bipolar disorder and major depression) were diagnosed far more frequently by our
      group than by referring psychiatrists. Patients whose diagnosis was changed were
      more likely to be given mood-stabilizing medication and tended to show more
      improvement than patients whose diagnosis was not changed. CONCLUSIONS: These
      findings raise the possibility that patients may not respond to treatment because
      incorrect diagnoses result in inappropriate treatment.

PMID- 1351482
TI  - Nutritional and hormonal regulation of mRNA levels of lipogenic enzymes in
      primary cultures of rat hepatocytes.
AB  - The effects of nutrients and hormones on the mRNA levels of acetyl-CoA
      carboxylase, fatty acid synthase, malic enzyme, and glucose 6-phosphate
      dehydrogenase were examined in primary cultures of rat hepatocytes during the
      process of induction. The addition of both glucose and insulin to the culture
      medium markedly enhanced the lipogenic enzyme mRNA induction due to either of
      them, in 16 h. Fructose or glycerol proved to be an effective substitute for
      glucose, suggesting that glycolytic metabolites were involved in the mRNA
      induction. It is remarkable that mRNA induction of acetyl-CoA carboxylase was the
      most sensitive to glucose and also to insulin among the lipogenic enzymes.
      Polyunsaturated fatty acids markedly reduced the mRNA induction of lipogenic
      enzymes. Dexamethasone enhanced all the lipogenic enzyme mRNA induction by
      insulin. On the other hand, triiodothyronine addition greatly increased the mRNA
      concentrations of lipogenic enzymes, but dexamethasone decreased rather than
      increased the mRNA induction by triiodothyronine. The effects of insulin on the
      induction of the lipogenic enzyme mRNAs were similar, but those of
      triiodothyronine were not. Triiodothyronine markedly enhanced malic enzyme mRNA
      induction by insulin with dexamethasone, and tended to enhance the induction of
      the acetyl-CoA carboxylase and fatty acid synthase mRNAs, but not that of glucose
      6-phosphate dehydrogenase mRNA. It appeared that insulin and triiodothyronine
      synergistically enhanced lipogenic enzyme mRNA induction by glucose, but the
      mechanisms were different.

PMID- 1351484
TI  - Restriction endonuclease-fragment polymorphisms of oral viridans streptococci,
      compared by conventional and field-inversion gel electrophoresis.
AB  - Oral streptococci formerly classified as Streptococcus sanguis or Streptococcus
      mitis have recently been divided into four species. Two additional species have
      also been proposed for this group. Each species is genetically distinct, but they
      have many traits in common, which makes it difficult for clinical isolates to be
      identified by phenotypic tests. Genotypic comparison may provide an alternative
      approach. This study used DNA fingerprint analysis for comparison of genotypes of
      21 reference strains--classified as Streptococcus gordonii, Streptococcus
      sanguis, Streptococcus oralis, "Streptococcus parasanguis", or "Streptococcus
      crista" in previous DNA hybridization studies--and 17 clinical and laboratory
      strains placed in those groups on the basis of phenotypic tests. HinDIII and
      PvuII digests were run in conventional horizontal agarose gels. SfiI digests of
      reference strains and two laboratory strains were run in field-inversion gels.
      Fingerprint patterns were compared by visual examination, cluster analysis of
      densitometric traces, and lane-matching software. Only two "S. crista" strains
      and two parent mutant lineages showed fingerprint patterns that were identical by
      visual examination. Fingerprint patterns of all other strains were unique.
      Cluster analysis results could not be considered valid, since replicate lanes in
      different gels were not grouped together. HinDIII and PvuII digests contained too
      many bands for correct matching by lane-matching software. SfiI digests were
      correctly matched by computer, with the same results as visual examination.
      Results indicate that the diversity of strains within these streptococcal species
      was too great to permit species identification by DNA fingerprint patterns. This
      genotypic diversity suggests that isolates from unrelated hosts may have been
      separate for long periods of time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351483
TI  - Restriction fragment length polymorphism analysis of the fimbrillin locus, fimA,
      of Porphyromonas gingivalis.
AB  - With hybridization probes derived from the fimbrial locus of Porphyromonas
      gingivalis strain 381, fimA381, restriction fragment length polymorphisms (RFLPs)
      were examined at the fimbrillin locus in 39 human and animal strains of this
      species. The 39 strains were subdivided into nine RFLP groups (I-IX) after
      genomic digests were probed with the internal coding sequence of the fimA381
      gene. Thirty-three strains showed one or more AluI fragments of moderate-to-high
      homology (greater than or equal to 77%) with the internal coding sequence of
      fimA381. These strains were distributed into the first seven RFLP groups, based
      solely on the size of the major hybridizing AluI fragment. Five human strains
      (RFLP Group VIII) had only one AluI fragment that hybridized very poorly with
      this probe. One animal strain did not have homology at all (RFLP Group IX). When
      all AluI fragments that hybridized with fimA381 were analyzed, RFLP groups I-VIII
      were further differentiated into 25 distinct RFLP patterns. Hybridizations were
      also performed with the internal coding sequence of fimA381 to probe PstI genomic
      digests of selected strains that appeared to have lesser homology with fimA381.
      These hybridizations were performed to determine the level and location of the
      region of poor homology within the fimA genes of these strains. The results
      suggested that fimbrial coding sequences are more commonly conserved between
      these strains in the 5'-region of the fimA locus (greater than or equal to 92%
      sequence homology).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351485
TI  - Draft recommendations from the Pew Health Professions Commission.

PMID- 1351486
TI  - Effect of drying period and soil moisture on egg hatch of the tadpole shrimp
      (Notostraca: Triopsidae).
AB  - Tadpole shrimp (Triops spp.) are potential biological control agents against
      larval mosquitoes in temporary ponds and flood-irrigated fields. In some rice
      field situations, however, they may become pests that uproot and eat young rice
      plants. In cursory observations, it has been reported that tadpole shrimp eggs do
      not readily hatch on flooding when the soil or substrate containing eggs is moist
      before flooding. The relationship between drying (moisture content) of soil and
      tadpole shrimp hatch was determined in studies conducted in mesocosms at the
      University of California Aquatic and Vector Control Research facilities at
      Riverside and at Oasis in the Coachella Valley of southern California. In
      laboratory hatching trials, an increase in hatch of Triops longicaudatus
      (LeConte) with declining soil moisture content was demonstrated (t = 8.4, P less
      than 0.001; r2 = 0.76). In field trials in mesocosms at Riverside, egg hatch
      increased with increased drying period and declining soil moisture content (G =
      29.8, P less than 0.01). No hatch of eggs occurred after 3 d of drying, when soil
      moisture content was high, but a high level of hatching occurred after 7 and 14 d
      of drying, when soil moisture declined to low levels. At Oasis, soil moisture did
      not decrease with drying time because of porous soil and capillary action of
      water from adjacent flooded mesocosms and thick vegetation covering the pond
      bottoms. Therefore, hatch rates at Oasis were not associated with the length of
      the drying period (G = 35, P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351487
TI  - AIDS: sharing the challenge--changing attitudes. Conference organized by Anglia
      Polytechnic and Nursing Standard at the Officers' Mess, Imperial War Museum,
      Duxford, England, 2 December 1991.

PMID- 1351488
TI  - The neurohormonal hypothesis: a theory to explain the mechanism of disease
      progression in heart failure.
AB  - Because physicians have traditionally considered heart failure to be a
      hemodynamic disorder, they have described the syndrome of heart failure using
      hemodynamic concepts and have designed treatment strategies to correct the
      hemodynamic derangements of the disease. However, although hemodynamic
      abnormalities may explain the symptoms of heart failure, they are not sufficient
      to explain the progression of heart failure and, ultimately, the death of the
      patient. Therapeutic interventions may improve the hemodynamic status of patients
      but adversely affect their long-term outcome. These findings have raised
      questions about the validity of the hemodynamic hypothesis and suggest that
      alternative mechanisms must play a primary role in advancing the disease process.
      Several lines of evidence suggest that neurohormonal mechanisms play a central
      role in the progression of heart failure. Activation of the sympathetic nervous
      system and renin-angiotensin system exerts a direct deleterious effect on the
      heart that is independent of the hemodynamic actions of these endogenous
      mechanisms. Therapeutic interventions that block the effects of these
      neurohormonal systems favorably alter the natural history of heart failure, and
      such benefits cannot be explained by the effect of these treatments on cardiac
      contractility and ejection fraction. Conversely, pharmacologic agents that
      adversely influence neurohormonal systems in heart failure may increase
      cardiovascular morbidity and mortality, even though they exert favorable
      hemodynamic effects. These observations support the formulation of a
      neurohormonal hypothesis of heart failure and provide the basis for the
      development of novel therapeutic strategies in the next decade.

PMID- 1351489
TI  - Protective effect and duration of action of inhaled formoterol and salbutamol on
      exercise-induced asthma in children.
AB  - The magnitude and duration of protection against exercise-induced asthma (EIA)
      afforded by salbutamol and the new, long-acting beta 2-agonist, formoterol, were
      compared in a double-blind, placebo-controlled crossover study. Twelve children
      with asthma and EIA (greater than 25% fall from baseline at a pretrial exercise
      test) were studied on 3 different days receiving, in random order, either
      formoterol, 12 micrograms, salbutamol, 200 micrograms, or placebo by inhalation.
      The effect on EIA was evaluated by standardized treadmill-exercise tests repeated
      at the following times after medication: 1/2 hour (test 1), 3 hours (test 2),
      and, if the trial drug still demonstrated an effect, 5 1/2 hours (test 3) and 8
      hours (test 4). The mean (SD) maximum percent fall in FEV1 at the pretrial test
      was 45% (14%). Placebo treatment had no effect on EIA. The mean (SD) maximum
      percent fall in FEV1 was 44% (14%) (test 1) and 39% (13%) (test 2) (not
      significant). Salbutamol offered good protection against EIA after 1/2 hour
      (percent fall in FEV1, 18% [18%]; p less than 0.02) but was not significantly
      different from that of placebo after 3 hours, 39% (13%) fall in FEV1. Formoterol
      blocked EIA in all the children and demonstrated a significant effect in most
      children for at least 8 hours. The percent fall in FEV1 after the various tests
      were 8% (16%) (test 1), 10% (9%) (test 2), 18% (15%) (test 3), and 18% (7%) (test
      4; N = 9) (all tests, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351490
TI  - Molten metal burn of the foot: a preventable injury.
AB  - Molten metal burns of the feet remain a common injury to foundry workers. A case
      is reported of a foundry worker who sustained circumferential molten metal burns
      of the distal foot and toes necessitating amputation of four toes. This severe
      injury could easily have been prevented by the use of protective footwear and
      spats.

PMID- 1351491
TI  - Immunocytochemical analysis of chromaffin cell proliferation in vitro.
AB  - The bromodeoxyuridine (BrdU) incorporation technique for immunocytochemical
      labeling of S-phase nuclei was optimized for the study of chromaffin cell
      proliferation. Sequential fixation in ethanol followed by paraformaldehyde, and
      the use of DNAse to render incorporated BrdU accessible to antibody, permitted
      permanent double staining for BrdU and tyrosine hydroxylase. The efficacy of the
      technique was demonstrated in microcultures of dissociated neonatal rat adrenal
      glands, in which chromaffin cells exhibited proliferative responses to nerve
      growth factor and fibroblast growth factor similar to those previously
      demonstrated by autoradiography. Growth factor responsiveness was observed in
      both serum-containing and serum-free medium.

PMID- 1351492
TI  - Antibiotic-resistant enterococci.
AB  - Enterococci have emerged as an important cause of nosocomial infection.
      Successful antibiotic treatment of serious enterococcal infection usually depends
      on the synergistic bactericidal effect achieved by the combination of a cell wall
      active agent, such as ampicillin or a glycopeptide, and an aminoglycoside.
      However, the prevalence of enterococci resistant to one or more of these
      antibiotics is increasing, and has resulted in serious therapeutic difficulties.
      The mechanisms of antibiotic resistance, and the epidemiology, laboratory
      diagnosis and management of infection with antibiotic-resistant enterococci are
      discussed.

PMID- 1351493
TI  - Characterization of methicillin-resistant Staphylococcus aureus associated with
      nosocomial infections in the University Hospital, Kuala Lumpur.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) as a hospital pathogen has
      presented many clinical problems in the University Hospital, Kuala Lumpur,
      Malaysia since 1978. The need for control of spread of these organisms became
      evident by 1985 when it was noted that the incidence of MRSA among S. aureus
      isolated from hospital inpatients had increased from 11.5% in 1979 to 18.8% in
      1985. The characteristics of 50 MRSA isolates associated with nosocomial
      infections in the hospital are described here. The predominant strains produced
      Type IV coagulase and 84% of isolates studied showed moderate to high resistance
      to methicillin with MIC values of 25 mg l-1 or higher. All the MRSA isolates that
      could be phagetyped were susceptible to Group III phages, with 76.6% of the
      isolates being susceptible to phage 85. At least 10 different patterns were
      distinguishable by plasmid typing, the majority of isolates harbouring up to four
      small plasmids.

PMID- 1351494
TI  - Microbiology of postoperative wound infection: a prospective study of 1770
      wounds.
AB  - A prospective study of postoperative wound infection was carried out over a 12
      month period. Intra-operative swabs from the patients' anterior nares, the opened
      viscus and parietes were cultured using standard bacteriological techniques. Of
      the 1770 wounds studied, 167 (9.4%) became infected. Wound infection rates,
      according to clinical wound types, were clean 5.9%, clean-contaminated 10.7%,
      contaminated 24.3% and dirty 52.9%. The figures according to microbiological
      wound types were clean 4.7%, and potentially, lightly and heavily contaminated
      15.3%, 22.1% and 30.2% respectively. The commonest causative organisms were
      Staphylococcus aureus 23.7%, Escherichia coli 16.9%, Staphylococcus epidermidis
      13.5% and Pseudomonas aeruginosa 13.0%. When isolated intra-operatively,
      Enterobacter spp., Proteus spp., Klebsiella spp. and P. aeruginosa appeared to
      have a high probability of causing postoperative wound infection, but the intra
      operative isolation of Bacteroides sp. was a poor predictor of subsequent wound
      infection.

PMID- 1351495
TI  - Bacteriophage phi X-174 as an aerobiological marker for surgical plume generated
      by the electromagnetic field focusing system.
AB  - The aerosol of surgical plume could be measured effectively with the use of
      bacteriophage phi X-174 as a biological marker, in contrast to previous
      methodologies reported by others. Recovery of virus plaque-forming units was
      highest from hydrophobic polytetrafluoro-ethylene membranes compared to
      hydrophobic polycarbonate screen filters or polyvinylidene difluoride depth
      filters, indicating that the method of virus recovery strongly affects the
      utility of a virus as an aerobiological marker. With this new method, surgical
      plume was indeed found in significant amounts when cutting tissue phantoms made
      with agar containing virus. The Electromagnetic Field Focusing System was used,
      which is a new thermal surgical device. The nominal power setting did not appear
      to be a factor in the amount of virus recovered. However, when pulse modulating
      the power by adjusting the crest factor from 1.4 to 4.3, a measure of the duty
      cycle for power delivery which adjusted the device from its cutting to
      haemostatic mode, a nearly five-fold increase in surgical plume, as evidence by
      the recovery of phi X-174 plaque forming units, was seen. The data indicate that
      bacteriophage phi X-174 can be used effectively as an aerobiological marker for
      aerosols generated during clinical procedures, and reinforce the need to use a
      safety vacuum during aerosol generating procedures. The availability of a safe
      and economical biological marker for aerosols from clinical procedures, which may
      lead to acquired infections in hospital personnel, makes evaluation of procedures
      and containment systems markedly easier. The data also indicates that surgical
      plume biohazard may be present in other techniques that employ pulse modulation
      including surgical lasers and electrocauteries.

PMID- 1351496
TI  - Bacterial contamination and the effect of filters in anaesthetic circuits in a
      simulated patient model.
AB  - In order to investigate bacterial contamination of anaesthetic breathing circuits
      and means of prevention of this, six different laboratory experiments were
      performed. These experiments involved the bacterial contamination of Drager
      Narkose Spiromat 650 and Drager AV-1 circle system circuits and of an isolated
      soda lime carbon dioxide absorber. The effects of anaesthetic gas, gas flow rate
      and the incorporation of a hydrophobic membrane heat and moisture exchanging
      bacterial/viral filter (HMEF) at the patient end of these circuits were
      investigated. It was found that without a HMEF the whole interior of the
      anaesthetic circuits became contaminated with bacteria. Components closest to the
      simulated patient showed the highest levels of contamination. Higher gas flows
      were associated with decreased levels of circuit contamination, presumably
      because more bacteria were expelled from the system. Halothane (1 volume %) and
      soda lime were not found to have any demonstrable bactericidal action. The
      presence of a HMEF between the simulated patient and the Y-piece prevented any
      detectable contamination from reaching the circuit. Consequently, the presence of
      a HMEF provides protection of the anaesthetic circuit as well as other patients,
      healthcare workers and the environment.

PMID- 1351497
TI  - Handwashing and disinfection of heavily contaminated hands--effective or
      ineffective?
AB  - Hands are among the principal vehicles for transfer of nosocomial pathogens in
      hospitals. Often, outbreaks of infection are thought to be caused by a lack of
      compliance with handwashing guidelines, rather than due to the inadequacy of the
      handwashing agents used. In this study the effectiveness of proper handwashing
      and the use of three different hand disinfectants: ethanol 70% (E), isopropanol
      40% (I) and alcoholic chlorhexidine (70%) (AC) was compared using three
      volunteers whose fingertips were heavily contaminated with a succession of
      bacteria including: Enterococcus faecalis, Staphylococcus aureus, Escherichia
      coli and Enterobacter cloacae. After each contamination, thorough handwashing and
      application of one disinfectant on the hands were performed three times.
      Fingerprint-samples were taken before and 1 min after application of the
      disinfectants. Thorough handwashing with an ordinary liquid soap ('Sterisol') did
      not reduce the confluent growth of bacteria on fingertips for any of the species
      used (197 examinations). Only AC had a significant effect on fingers heavily
      contaminated with S. aureus (126 examinations; AC compared with E and I; P less
      than 0.0002 and P less than 0.0002 respectively), but did not completely
      eradicate the bacteria. After contamination with Ent. cloacae (118 examinations),
      none of the three agents were particularly effective, but E and AC seemed to be
      somewhat more effective than I (P less than 0.0002 and P less than 0.01
      respectively). When successive contamination was performed using all bacterial
      species, AC was the most effective decontaminant. However, Ent. cloacae was still
      present on the fingertips after 15 repeated courses of handwashing and
      applications of disinfectants. Bathing of hands in AC for 20s completely
      eradicated all bacteria from the hands. The study demonstrates that, when heavily
      contaminated, an ordinary handwashing followed by disinfectants is not enough to
      eradicate potentially pathogenic bacteria from the hands.

PMID- 1351498
TI  - A randomized prospective study to compare cefotetan with cefuroxime plus
      metronidazole as prophylaxis in elective colorectal surgery.
AB  - This study compares the efficacy of cefotetan with the combination of cefuroxime
      plus metronidazole as antibiotic prophylaxis in elective colorectal surgery when
      given over the first 24 h postoperatively. There was no significant difference in
      wound infection rates between the two groups (14.7% for cefotetan and 13.9% for
      cefuroxime plus metronidazole), or the rates of other infective complications.
      Adverse reactions occurred with equal frequency in both treatment groups and no
      serious side effects occurred. Cefotetan is a safe and effective antibiotic for
      use as prophylaxis in elective colorectal surgery. Its advantages are that it is
      a single agent with a spectrum covering both aerobic Gram-negative rods and
      anaerobic organisms and, because of its long half-life, needs only to be given at
      12-hourly intervals.

PMID- 1351499
TI  - Postoperative wound infection at a university hospital in Jeddah, Saudi Arabia.
AB  - A prospective study was made of 1418 surgical wounds at the 250-bed King
      Abdulaziz University Hospital in Jeddah, Saudi Arabia. Daily examinations of
      wounds, cultures of all suspicious wounds and 28 days outpatient clinic follow-up
      were performed. The overall infection rate was 9%. The infection rate after clean
      surgery was 9.5%. High rates of infections were noted after colon resection
      (19%), caesarean section (19%), abdominal hysterectomy (10%) and cholecystectomy
      (10%). The infection rates after appendectomy, mastectomy and herniorrhaphy were
      approximately 7%. A lower rate of infection was seen after thyroidectomy (2%).
      The incidence of infection was significantly related to pre-operative stay in
      hospital and to duration of operation.

PMID- 1351500
TI  - Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate
      chronic infection with Toxoplasma gondii.
AB  - C57BL/6 mice chronically infected with an avirulent strain (ME-49) of Toxoplasma
      gondii were used to study the mechanisms by which T lymphocytes and IFN-gamma
      prevent reactivation of latent infection. Infected animals were treated with mAb,
      either anti-CD8, anti-CD4, anti-CD4 plus anti-CD8, anti-IFN-gamma, or anti-CD4
      plus anti-IFN-gamma and the mice followed for survival, histopathology, cyst
      numbers, and spleen cell cytokine responses. In agreement with previously
      published findings, treatment with anti-IFN-gamma antibodies fully reactivated
      the asymptomatic infection, inducing massive necrotic areas in the brain with the
      appearance of free tachyzoites and death of all animals within 2 wk. Mice treated
      with the combination of anti-CD4 plus anti-CD8 antibodies showed augmented
      pathology and mortality nearly identical to the anti-IFN-gamma- treated animals.
      In contrast, treatment with anti-CD4 or anti-CD8 mAb alone failed to result in
      significantly enhanced brain pathology or mortality. In additional experiments,
      full reactivation of infection was observed in mice treated with anti-CD4 plus
      anti-IFN-gamma indicating that CD4+ lymphocytes are not required for the
      pathology resulting from IFN-gamma neutralization. Cytokine measurements on
      parasite Ag-stimulated spleen cells from mAb-treated mice indicated that both
      CD4+ and CD8+ cells produce IFN-gamma whereas only CD4+ cells contribute to
      parasite Ag-induced IL-2 synthesis. Together, these results suggest that CD4+ and
      CD8+ lymphocytes act additively or synergistically to prevent reactivation of
      chronic T. gondii infection probably through the production of IFN-gamma.

PMID- 1351501
TI  - Migration of recombinant IL-2-activated T and natural killer cells in the
      intercellular space of human H-2 glioma spheroids in vitro. A study on adhesion
      molecules involved.
AB  - The migration of rIL-2-activated T and NK cells into the intercellular space of
      glioma tissue was studied using multicellular spheroids grown from the human H-2
      glioblastoma cell line as targets. Lymphocytes of all analyzed subtypes migrated
      into the spheroids, but CD56+ cells were particularly migratory. Lymphocytes and
      the H-2 tissue expressed adhesion molecule subunits for the following potential
      cell-cell or cell-matrix interactions: alpha 3 beta 1 (VLA-3) to fibronectin,
      laminin, and collagen; alpha 4 beta 1 (VLA-4) and alpha 5 beta 1 (VLA-5) to
      fibronectin; alpha 6 beta 1 (VLA-6) to laminin; alpha 4 beta 1 to VCAM-1; alpha L
      beta 2 (Leu-CAMa/LFA-1) to CD54 (ICAM-1); CD44 to fibronectin, collagen, laminin,
      hyaluronate; CD2 to CD58 (LFA-3); and CD56 (N-CAM) to CD56. In the H-2 tissue,
      CD54 and VCAM-1 were expressed as a gradient. The expression of CD54 was weak in
      the peripheral zone and the expression was stronger in the quiescent deeper zone,
      whereas the distribution of VCAM-1 showed an inversed pattern. The low expression
      of CD54 was up-regulated along the frontier of migrating lymphocytes. The
      migration was almost totally prevented by the anti-CD18 (beta 2) mAb IB4 and
      TS1/18, and also strongly inhibited by the anti-CD54 mAb LB-2. Instead, mAb known
      to inhibit the binding of beta 1 integrins to fibronectin were not significantly
      inhibitory. However, a combination of the GPEILDVPST and GRGDS peptides, which
      compete for the binding of alpha 4 beta 1 and alpha 5 beta 1 to fibronectin and
      may also affect other adhesion systems, partially prevented migration.

PMID- 1351502
TI  - Induction and suppression of delayed-type hypersensitivity to non-MHC antigens
      during lethal graft-versus-host reaction.
AB  - A delayed-type hypersensitivity reaction (DTH) to non-MHC Ag was detected during
      a lethal graft-vs-host reaction (GVH) induced by incompatibility for non-MHC Ag
      alone. In this model, when appropriate doses of B10.D2 bone marrow and lymphoid
      cells are grafted to irradiated (DBA/2 x B10.D2)F1 recipients, the ensuing GVH,
      directed against those DBA/2 non-MHC Ag absent from the B10.D2 background,
      results in virtually 100% mortality in less than 3 mo; donor alloimmunization
      against the host histocompatibility Ag considerably reduces mortality, and
      survival rates of 80 to 100% are common. The experiments reported here show that:
      1) the cell responsible for DTH induction expresses the CD4+ CD8- phenotype; 2)
      CD4+ cells likewise seem to play a predominant role in the pathology of lethal
      GVH in this genetic combination; 3) the alloimmunization protocol that abrogates
      mortality also abolishes GVH-associated DTH; and 4) this suppressive effect, as
      shown elsewhere for the protection against mortality, is mediated by CD4- CD8-
      "double negative" Thy-1+ CD3+ T suppressor cells. Thus, there is a good parallel
      between lethal GVH and its associated DTH as concerns both induction and
      suppression of the two phenomena, suggesting that mortality and DTH may represent
      different manifestations of a common underlying mechanism. Initiation of the
      effector phase of DTH in the adoptive transfer model seems to be dependent on the
      presence of a Thy-1+ double-negative cell in the transfer inoculum; the possible
      relationship of this double-negative cell to the Th-1-type CD4+ DTH-mediating
      cell recently shown to induce lethal GVH is discussed.

PMID- 1351503
TI  - Murine AIDS superantigen reactivity of the T cells bearing V beta 5 T cell
      antigen receptor.
AB  - A B cell line, B6-1710, that expresses the defective virus known to induce murine
      AIDS stimulates a large fraction of nonprimed splenic T cells. Analysis of the T
      cell population responding to the B6-1710 for TCR V beta-chain usage revealed
      that, in addition to the previously reported V beta 5-chain-positive T cells, T
      cells bearing V beta 11 and V beta 12 are also specifically enriched. We have
      established V beta 5+ T cell lines, clones, and hybridomas expressing identical
      TCR with different CD4/CD8 phenotypes and demonstrated that T cell reactivity to
      B6-1710 is, although not absolute, dependent on the presence of CD4 molecules.
      Further analysis of T cell hybridomas with known J beta-chain usage revealed that
      D beta- and J beta-chain usage do not play crucial roles in T cell reactivity to
      B6-1710 B cells. However, T cell hybridomas derived from TCR-V beta gene
      transgenic mice were found to be heterogeneous for their reactivity to B6-1710,
      suggesting that the V alpha-chains associating with the transgenic V beta-chain
      determine T cell responsiveness to B6-1710. These data clearly demonstrate that T
      cell reactivity to a murine AIDS virus expressing B cell line resembles that
      previously reported for Mls-like superantigens.

PMID- 1351504
TI  - The parasporal inclusion of Bacillus thuringiensis subsp. shandongiensis:
      characterization and screening for insecticidal activity.
AB  - The parasporal body of Bacillus thuringiensis subsp. shandongiensis was
      characterized in terms of its structure, protein composition, and toxicological
      properties against several types of insects. The crystals of B. thuringiensis
      shandongiensis appear to consist of a major protein of 144 kDa present in an
      spherical inclusion, as determined by transmission electron microscopy, titration
      curve analysis, and SDS-PAGE of the solubilized crystals. A second protein of ca.
      60 kDa is present in trace amounts and appears to be associated with a small bar
      shaped inclusion. The 144-kDa protein has been characterized by isoelectric point
      determination, N-terminal amino acid sequence analysis, amino acid analysis, and
      immunological cross reactivity. Its N-terminal amino acid sequence differed from
      that of other B. thuringiensis crystal proteins. The 144-kDa protein was not
      immunologically related to the crystal proteins of two toxic serovars (B.
      thuringiensis israelensis and B. thuringiensis kurstaki HD-1) and one nontoxic
      serovar (B. thuringiensis indiana), as shown in immunoblots probed with antiserum
      raised against the 144-kDa B. thuringiensis shandongiensis protein, the B.
      thuringiensis israelensis crystal proteins, and the trypsin resistant fragment of
      B. thuringiensis kurstaki P1 proteins. In contrast to most B. thuringiensis
      serovars, B. thuringiensis shandongiensis crystals did not dissolve at pH 12.
      Solubilization was achieved in sodium bicarbonate at pH 8.3 and in the presence
      of 25 mM dithiothreitol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351506
TI  - ICAM-1 expression in a spontaneously transformed human keratinocyte cell line:
      characterization by a simple cell-ELISA assay.
AB  - Interferon gamma (IFN-gamma) is known to induce ICAM-1 on keratinocytes (KC) in
      vitro, and its expression in vivo is correlated with epidermal T-cell
      infiltration in various dermatoses. However, the mechanisms for this cytokine
      mediated ICAM-1 expression are essentially unknown. We investigated the induction
      of ICAM-1 by IFN-gamma in HaCaT cells, a spontaneously transformed human KC cell
      line, using an immunoperoxidase-ELISA with the monoclonal antibody (MoAb) R6.5.
      HaCaT cells constitutively expressed low levels of ICAM-1, which were upregulated
      by IFN-gamma. The kinetics and dose response were similar to those published for
      primary KC, regardless of whether the HaCaT cells were cultured in low- or high
      calcium medium. ICAM-1 expression was increased significantly at 4 h with 500
      U/ml IFN-gamma, and reached a plateau (approximately 5 x greater than
      constitutive) by 24 h. At concentrations greater than 10 U/ml for 24 h, IFN-gamma
      induced ICAM-1 expression in a dose-dependent fashion (half maximal at 100 U/ml).
      TNF-alpha alone, and in synergistic combination with IFN-gamma, also upregulated
      the expression of HaCaT ICAM-1. IFN-gamma treatment of HaCaT cells increased the
      level of ICAM-1 mRNA and enhanced (approximately 3x) the adherence of
      fluorescently labeled (calcein) human T lymphoblasts, as determined by Northern
      blotting and an in vitro adhesion assay, respectively. Our findings suggest that
      HaCaT cells, in conjunction with a simple immunoperoxidase cell-ELISA, provide a
      reliable system for studying pharmacologic modulation of ICAM-1 on KC.

PMID- 1351505
TI  - Type I keratinocyte transglutaminase: expression in human skin and psoriasis.
AB  - A 92-kD transglutaminase (TGase K), expressed in human cultured keratinocytes and
      stratum corneum, catalyzes a critical step in the formation of the cornified
      envelope of terminal differentiation. A rabbit polyclonal antibody to TGase K was
      used to isolate overlapping cDNA clones from a human keratinocyte cDNA expression
      library. The cDNA clones were sequenced and unequivocally identified as TGase K
      by comparison to the N-terminal amino acid sequences of two cyanogen bromide
      fragments from the purified enzyme. The mRNA for Tgase K is expressed in cultured
      keratinocytes but not in A431 squamous carcinoma cells, in fibroblasts, or in
      other non-epithelial tissues and cells. Although TGase K protein expression is
      limited to the upper layers of normal epidermis, the mRNA is generally present
      throughout the epidermis, suggesting the possibility of post-transcriptional
      regulation. Precocious expression of TGase K protein occurs in psoriasis, and
      quantitative Northern blot analysis of TGase K mRNA from normal and involved
      epidermal biopsies from psoriasis patients suggests that TGase K mRNA levels are
      increased in psoriatic lesions. By using quantitative laser scanning confocal
      microscopy (LSCM) and in situ hybridization, the increase of the TGase K mRNA was
      in the range of 3-7 times in the psoriatic epidermis and was significantly higher
      compared with normal skin and with paired adjacent skin. Quantitative LSCM
      provides a powerful and direct method for analysis of gene expression in skin.

PMID- 1351507
TI  - Effects of ultraviolet radiation on murine epidermal Langerhans cells: doses of
      ultraviolet radiation that modulate ICAM-1 (CD54) expression and inhibit
      Langerhans cell function cause delayed cytotoxicity in vitro.
AB  - Low doses (100 J/m2) of ultraviolet B (UVB) radiation from sunlamp fluorescent
      FS20 tubes inhibit the ability of freshly isolated murine epidermal Langerhans
      cells (LC) to support anti-CD3 MoAb-induced T-cell mitogenesis and selectively
      inhibit the upregulation of ICAM-1 expression by LC without causing appreciable
      cytotoxicity in short-term (less than or equal to 24 h) incubations (J Immunol
      146:3347-3355, 1991). In the present study, epidermal cells (EC) were exposed to
      UVB radiation or were sham-irradiated and cultured for 24, 48, or 72 h when LC
      were recovered, enumerated, and assayed for simultaneous expression of I-A
      antigens and ICAM-1 by flow cytometry. UVB-irradiated LC that had been cultured
      for 24 h exhibited levels of I-A antigens comparable to those on unirradiated LC
      but expressed substantially less ICAM-1. After 48 and 72 h, cultured UVB
      irradiated LC expressed somewhat lower levels of I-A antigens and markedly less
      ICAM-1 than unirradiated controls. Although similar numbers of LC were recovered
      from cultures initiated with UVB-irradiated and unirradiated epidermal cells
      after 24 h, far fewer identifiable LC were recovered from cultures seeded with
      irradiated cells at 48 and 72 h (approximately 50 and approximately 10% of
      control, respectively). The effect of UVB radiation on the survival of LC in
      vitro was not reversible with exogenous TNF alpha (125 U/ml) alone or
      granulocyte/macrophage colony-stimulating factor (5 ng/ml) and IL-1 (50 U/ml) in
      combination, although these cytokines had modest effects on the expression of I-A
      antigens and ICAM-1 by cultured UVB-irradiated LC. Results of survival studies
      performed with enriched LC preparations demonstrated that UVB radiation was
      clearly cytotoxic for LC and did not merely downregulate surface expression of I
      A antigens or alter LC buoyant density. Exposure of LC to radiation from
      blacklight fluorescent (UVA) tubes (0.25 J/cm2) in the presence of 8
      methoxypsoralen (1 micrograms/ml; PUVA) or monochromatic UVC radiation (20 J/m2)
      also inhibited LC accessory cell function. Results of survival studies performed
      with EC that had been exposed to PUVA or UVC radiation before culture were
      similar to those of studies performed with UVB-irradiated cells, although PUVA-
      and UVC-induced LC cytotoxicity was much more pronounced 48 h after culture
      initiation than UVB-induced cytotoxicity. UVA radiation alone augmented LC
      recovery at 24 and 48 h, but did not influence I-A antigen or ICAM-1
      expression.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1351508
TI  - Belgrade virus: a new hantavirus causing severe hemorrhagic fever with renal
      syndrome in Yugoslavia.
AB  - Two biologically and genetically distinct hantaviruses were isolated from blood
      and urine specimens collected from four Yugoslavian patients with clinically
      severe hemorrhagic fever with renal syndrome (HFRS). Viral isolates from three
      patients, designated strains Belgrade 1-3, were distinct from Hantaan, Seoul,
      Puumala, and Prospect Hill viruses as determined by plaque-reduction
      neutralization tests and restriction analysis of enzymatically amplified M
      segment fragments. The fourth isolate, called Kraljevo, was indistinguishable
      from Hantaan virus. Strains Belgrade 1 and 2, like the Kraljevo strain, caused a
      fatal meningoencephalitis in newborn mice inoculated with 100 pfu of virus
      intracerebrally and intraperitoneally. Strain Belgrade 3 was much less
      neurovirulent, requiring 30,000 pfu of virus to cause fatal disease in mice.
      These data indicate that two distinct hantaviruses, one of which constitutes a
      new serotype, cause clinically severe HFRS in Yugoslavia.

PMID- 1351509
TI  - Streptococcal pyrogenic exotoxin A and streptolysin O enhance polymorphonuclear
      leukocyte binding to gelatin matrixes.
AB  - Autopsy data from cases of streptococcal toxic shock demonstrate accumulation of
      polymorphonuclear leukocytes (PMNL) within lung and soft tissue microvasculature.
      Because of the increased prevalence of streptococcal pyrogenic exotoxin A (SPEA)
      producing strains associated with streptococcal toxic shock syndrome, experiments
      were done to determine whether SPEA or streptolysin O (SLO, a thiol-activated
      cytolysin produced by all group A streptococci) could stimulate PMNL-dependent
      adherence mechanisms in vitro. SPEA (0.01-10 micrograms/5.5 x 10(6) PMNL) only
      modestly enhanced PMNL adherence over the entire range of concentrations tested.
      In contrast, SLO-induced PMNL binding was highly dose dependent (maximal binding,
      55.1 +/- 1.6% at 0.5 hemolytic units/5.5 x 10(6) PMNL) and was mediated by
      CD11/CD18 adherence glycoprotein.

PMID- 1351510
TI  - Genetic diversity of penicillin-resistant Neisseria meningitidis.
AB  - The genetic relatedness of 42 penicillin-resistant Neisseria meningitidis
      isolates obtained during a 2-year period from a single hospital was studied by
      multilocus enzyme electrophoresis and by restriction fragment length polymorphism
      (RFLP) analysis of penicillin-binding protein (PBP) 2 genes. The PBP 2 genes of 7
      susceptible strains gave identical RFLP profiles. Sixteen different PBP 2 RFLP
      profiles were found among the 42 resistant strains, but 4 were found in greater
      than 1 resistant isolate. Multilocus enzyme electrophoresis revealed a high level
      of genetic diversity. Four clusters of resistant strains could be distinguished
      at a genetic distance of 0.75. Resistant strains with the most common PBP 2 RFLP
      profile were restricted to one of these clusters and may be derived from a common
      ancestral strain. However, resistant strains with the 3 other common RFLP
      profiles were distributed in two or more of the clusters.

PMID- 1351512
TI  - [Multifunctional calmodulin-dependent protein kinase].

PMID- 1351511
TI  - Immunohistochemical characterization of endocrine cells in experimental exocrine
      pancreatic cancer in the Syrian golden hamster.
AB  - Fifty exocrine pancreatic adenocarcinomas and 57 benign tumors induced in Syrian
      hamsters by N-nitrosobis(2-oxopropyl)amine (BOP) were examined for the presence
      of argyrophil cells antiinsulin, -glucagon, -somatostatin, -pancreatic
      polypeptide (PP), -gastrin/CCK, -vasoactive intestinal polypeptide (VIP), and -
      neuron-specific enolase (NSE) reactive cells. Argyrophil - and antihormone
      reactive cells were found in the normal pancreatic ducts and in the acini, as
      well as in hyperplastic and atypical ducts/ductules, tubular complexes, benign
      lesions, and in 80% of ductal adenocarcinomas. Insulin and antiNSE-reactive cells
      were the most common, followed in decreasing frequency by glucagon, somatostatin,
      and PP cells. Antigastrin-/CCK-and -VIP-reactive cells were found in two cases.
      Argyrophil cells were present in about 60% of the tumors with Grimelius staining
      and in 55% of those with Churukian-Schenk staining. Insulin cells were seen in
      ductal cancer that had grown into a lymph node and in the lymph node metastases
      of another cancer. A novel finding was the presence of argyrophil and insulin
      cells within the lumen of some malignant glandular structures. Coexistence of
      several peptide cells was found in 52% of the cancers. The presence of argyrophil
      and hormone-producing cells in induced pancreatic ductal/ductular lesions further
      strengthens the existence of a close developmental relationship between exocrine
      and endocrine cells of the pancreas.

PMID- 1351513
TI  - [Urodynamic study on urinary disturbance after therapy of uterine cancer].
AB  - It is well known that urinary disturbance often appears after radical
      hysterectomy for uterine cancer and is aggravated by additional radiation
      therapy. The aim of this study is to elucidate the pathogenesis and to establish
      the treatment method of urinary disturbance after therapy for uterine cancer.
      Forty-five patients with urinary disturbance and ten normal controls were
      subjected to this study. Changes in clinical symptoms and findings in the
      Urodynamic study (UDS) in 12 severe cases were investigated before and after
      treatment with beta 2-stimulant (Mabuterol HCL). Clinical symptoms in cases
      treated by radiation therapy alone were rare and mild without any pad exchanges,
      and appeared 5 years after treatment for uterine cancer. Findings of UDS in these
      cases were mild low compliance of detrusor at maximum desire to void (Cmdv) and
      mild low bladder volume at maximum desire to void (Vmdv). In cases treated by
      radical hysterectomy alone, Cmdv decreased immediatelly after the operation and
      then maximum urethral closure pressure (cPura) gradually decreased. Concerning
      the cases treated by radical hysterectomy and radiation, severe low Cmdv and
      severe low Vmdv appeared 5 years after the treatment for uterine cancer in almost
      all cases, and low cPura appeared immediately after the operation in half of the
      cases. Treatment with beta 2-stimulant significantly improved urinary frequency,
      voided volume and urinary incontinence. In UDS findings, Vmdv and Cmdv were
      significantly improved by the treatment with beta 2-stimulant. The functional
      profile length and cPura value were not significantly changed. In uroflowmetry,
      the maximum flow rate and average flow rate were significantly improved by the
      treatment with beta 2-stimulant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351515
TI  - [Neurobiology of the peripheral nervous system].

PMID- 1351514
TI  - [Establishment and characterization of human ovarian fibrosarcoma cell line and
      its sensitivity to anticancer agents].
AB  - We succeeded in establishing a cell line (KEN-3) for subculture from a
      fibrosarcoma which originated in the ovary in a girl aged 17 years. Its
      characteristics and sensitivity to anticancer agents are reported in this paper.
      1. Characteristics of established cell line. Lined cells consist of
      multinucleated giant cells mixed among many spindle-shaped cells. They grow in
      small colonies and have none of the pavement-like arrangement characteristic of
      epithelial tumor cells. The number of chromosomes ranged from 45 to 128 (mode:
      pseudo-triploidy region, 65). The doubling time, cellular density and plating
      efficiency were 76.9 hours, 5.4 x 10(5)/cm2 and 30.2%, respectively. Concerning
      tumor markers, CEA and sialyl SSEA-1 were only produced in small quantities.
      Subculture was possible subcutaneously in the nude mouse with no capacity for the
      production of ascites. 2. Susceptibility to anticancer agents and GP170
      expression. The in vitro susceptibility to about 12 types of anticancer agents
      was investigated with the MTT assay. IC50/PPC was shown to be less than 1 for
      Adriamycin only. The sensitivity to CDDP (IC50/PPC: 4.8) was low, and no
      sensitivity was observed at all to DTIC, which is used frequently for mesenchymal
      tumors. GP170 (mdr-1 products) was positive in established cells in
      immunohistochemical stain.

PMID- 1351516
TI  - [Therapy of pancreatitis].

PMID- 1351517
TI  - [Current concept on therapy of asthma and pollenosis].

PMID- 1351518
TI  - [Diagnosis and therapy of acute gastritis].

PMID- 1351519
TI  - Recent advances in the study of ionizing radiation damage and repair.
AB  - This workshop, organized under the auspices of the EC Concerted Action Programme
      on DNA Repair and Cancer, was held at the CRC Gray Laboratory, Northwood,
      Middlesex, UK, 23-25 October 1991. The 42 participants were drawn mainly from
      laboratories participating in the EC Concerted Action, with a few visitors from
      elsewhere. The discussions centred on the increasing convergence of classical
      radiobiology and biophysics with molecular biology and mammalian cell genetics to
      study mechanisms of DNA strand break accumulation and repair following exposure
      to ionizing radiation. There was a strong emphasis on the application of this
      research both to cancer radiotherapy and to detection of individuals at risk from
      cancer due to exposure to ionizing radiation. The first two days were organized
      as six workshop sessions; on the third day we joined forces with Julie Denekamp
      and dedicated a session to the memory of our late friend and colleague, Nic
      McNally. The rest of this day was devoted to reviews by his colleagues and
      collaborators of the fields of research to which he contributed so much. An
      evening of music and readings, organized by Joanna and Rachel McNally, completed
      the memorial. Here we review the first seven sessions of the workshop,
      emphasizing the more recent approaches and the new information they have given
      us.

PMID- 1351520
TI  - A comparison of the chemical repair rates of free radical precursors of DNA
      damage and cell killing in Chinese hamster V79 cells.
AB  - One of the important temporal stages of radiation action in cellular systems is
      the chemical phase, where oxygen fixation reactions compete with chemical repair
      reactions involving reducing agents such as GSH. Using the gas explosion
      technique it is possible to follow the kinetics of these fast (greater than 1 ms)
      reactions in intact cells. We have compared the chemical repair kinetics of the
      oxygen-dependent free radical precursors leading to DNA single-strand and double
      strand breaks, measured using filter elution techniques, with those leading to
      cell killing in V79 cells. The chemical repair rates for DNA dsb (670s-1 at pH
      7.2 and 380s-1 at pH 9.6) and cell killing (530s-1) were similar. This is in
      agreement with the important role of DNA dsb in radiation induced cell lethality.
      The rate for DNA ssb precursors was significantly slower (210s-1). The difference
      in rate between DNA ssb and dsb precursors may be explained on the basis of a dsb
      free radical precursor consisting of a paired radical, one radical on each
      strand. The instantaneous probability of one or other of these radicals being
      chemically repaired and not proceeding to form a dsb will be twice that of ssb
      radical precursor. This agrees well with the concept of locally multiply damaged
      sites (LMDS) produced from clusters of ionizations in DNA (Ward 1985).

PMID- 1351521
TI  - Characterization of two radiation-induced lesions from DNA: studies using
      nuclease P1.
AB  - Exposure of DNA oligomers to ionizing radiation in oxygenated solution reveals
      that the two lesions formed in highest yield are the 8-hydroxy modification of
      guanine and the formamido remnant of thymine. The effect of these lesions on the
      hydrolysis of the phosphodiester bond by nuclease P1 was studied. Whereas the 8
      hydroxyguanine lesion does not affect hydrolysis of the adjacent 3' phosphoester
      bond by nuclease P1, the formamido lesion markedly retards hydrolysis. Consistent
      with the oligomer results, digestion of irradiated DNA polymer by nuclease P1
      plus acid phosphatase yielded the 8-hydroxyguanine lesion, obtained as the
      modified nucleoside, and the formamido lesion, obtained as a modified
      dinucleotide.

PMID- 1351522
TI  - Constraints on energy deposition and target size of multiply damaged sites
      associated with DNA double-strand breaks.
AB  - We suggest that the observed experimental data on relative double-strand break
      (dsb) yield as a function of radiation quality can act as valuable constraints in
      defining the type of energy deposition which causes this basic lesion in
      radiation biology. Both heavy-ion and alpha-particle data show sufficient trends
      for quantitative comparisons with calculation to be made. We use the technique of
      track-structure simulation and search for energy-deposition clusters (containing
      at least a given number of ionizations in a given diameter) whose relative
      frequencies (compared to sparsely ionizing radiation) correlate with the relative
      biological effects (RBEs) for dsb induction. We conclude that locally multiply
      damaged sites (LMDS) which cause dsb are probably energy depositions of at least
      two to five ionizations localized, respectively, in sites of diameters of 1-4 nm.
      Although our derived cluster sizes should be viewed in light of the quality of
      the experimental data and uncertainties in the computer simulations at the
      nanometre level, it is unlikely that these estimates of cluster sizes would
      change greatly.

PMID- 1351523
TI  - DNA damaging and cell cycle effects of the topoisomerase I poison camptothecin in
      irradiated human cells.
AB  - This study addressed the potential radiosensitizing and DNA-damaging actions of
      the DNA topoisomerase I poison camptothecin (CPT) on SV40 transformed normal
      (MRC5CVI) and ataxia-telangiectasia (AT5BIVA) fibroblast cell lines. In both cell
      lines CPT induced a dose-dependent delay of cells in S phase, followed by a dose
      dependent trapping in G2/M phase. Acute X-irradiation produced patterns of G2/M
      arrest and S-phase delay similar to those observed for CPT in the MRC5CVI cell
      line, but no S phase delay was observed in the AT5BIVA cell line consistent with
      the ataxiatelangiectasia phenotype of this cell line. X-irradiation of CPT
      treated cells resulted in additive prolongation of S phase delay in MRC5CVI
      cultures and additive effects for cell killing in both cell lines. The potential
      for topoisomerase I-DNA cross-linking by CPT was not altered by 24h pretreatment
      with CPT, or by acute X-irradiation. Hypersensitivity of AT5BIVA to CPT was not
      attributable to elevated levels of complex trapping. These findings suggest that
      in a rapidly proliferating human tumour there is unlikely to be synergistic
      therapeutic gain when the two agents are used concurrently, and that previously
      reported radiosensitization by CPT is restricted to G0 phase cells.

PMID- 1351524
TI  - Induction of lacI- mutations in Escherichia coli cells after single and split
      dose irradiation.
AB  - In the lacI system of Escherichia coli, X-ray mutagenesis follows a linear
      quadratic curve with suppression; the survival curve is exponential. Dose
      fractionation leads to nearly complete repair of premutational lesions during an
      incubation interval of 3.5 h. Repair starts with a delay of 1.5-2 h, suggesting
      the involvement of an inducible repair/mutation fixation system. The dose
      dependence of mutagenesis is described by a simple model assuming two hits being
      required. A probable explanation might be that the premutagenic lesions consist
      of two closely spaced lesions on the opposite strands of the DNA molecule.

PMID- 1351525
TI  - The effect of fluoride on photodynamic-induced fluorescence changes of aluminium
      phthalocyanine in Chinese hamster cells.
AB  - Fluence-dependent changes in the fluorescence of aluminium phthalocyanine (AlPc)
      were measured in Chinese hamster ovary (CHO) cells using digital fluorescence
      microscopy of single cells and spectrofluorimetry of cell suspensions. During
      illumination the fluorescence initially increased and later progressively
      decreased. In the presence of fluoride, which protects against phototoxicity of
      AlPc by forming a fluoroaluminium complex, there was no initial increase in
      fluorescence: it decreased about 10 times faster than in the absence of fluoride.
      Qualitatively similar results were observed using single-cell fluorescence
      microscopy, which also showed the dye to be mostly localized in cytoplasmic
      organelles and membranes. The pattern of localization did not change during
      illumination. Concomitant assays of dye extracted from cells revealed little
      photodegradation that could not account for the fluorescence changes. The
      absorption spectra of AlPc-loaded cells showed some aggregation of the dye prior
      to light exposure. During illumination the dye was initially monomerized and
      subsequently progressively reaggregated. In the presence of fluoride no
      monomerization was seen, and the aggregation proceeded at a much faster rate. It
      is concluded that the fluorescence changes are not due to major relocalization of
      AlPc in the cells, but to light-induced monomerization followed by reaggregation.
      The protective effect of fluoride may be due to the enhanced aggregation rate,
      because aggregated dye molecules are photochemically inactive. Because D2(0)
      affects neither the initial enhanced fluorescence in the absence of fluoride nor
      the rapid decrease in its presence it appears that 1O2 is not involved in the
      photodynamic reactions leading to these changes.

PMID- 1351526
TI  - PIXE determination of photosensitizer tissue distribution in mice bearing S180
      tumour sensitized with GaCl-tetrasulphophthalocyanine.

PMID- 1351527
TI  - Study of dose-rate and split-dose effects on the in vitro micronucleus yield in
      human lymphocytes exposed to X-rays.
AB  - This paper reports the effects of changes in dose-rate and dose-fractionation on
      the micronucleus (MN) yield in human lymphocytes exposed to 250 kV X-rays. For
      the investigation of dose-rate effects whole blood samples of four healthy donors
      were irradiated with doses ranging from 1 to 4 Gy given at various dose-rates
      between 0.2 and 40 Gy/h. For the higher doses (3 and 4 Gy) a decline in the MN
      yield became apparent when the dose-rate was reduced below 1.6 Gy/h. This effect
      was enhanced systematically by a further lowering of the dose-rate. For lower
      doses (1 and 2 Gy) the reduction in the MN yield was less pronounced: only a
      small effect was observed for two donors when a dose of 2 Gy was administered at
      a dose-rate of 0.2 Gy/h. In the split-dose experiment a dose of 4 Gy was
      delivered either as a single exposure or in two fractions of 2 Gy, separated by
      time intervals ranging from 30 min to 10 h. A continuous decrease of the MN yield
      with increasing interfraction time is observed: after an initial fast decline a
      further slight reduction in the MN yield occurs. The observed dose-rate and split
      dose effects on the MN yield can be attributed to repair of sublethal damage.

PMID- 1351528
TI  - Induction of chromosome aberrations by monochromatic X-rays with resonance energy
      of phosphorus K-shell absorption edge.
AB  - The induction of chromosome aberrations by monochromatic soft X-rays with
      energies corresponding to the K-shell absorption edge of phosphorus has been
      studied in density-inhibited mouse m5S cells. The frequency of dicentrics was
      markedly enhanced when the cells were irradiated with energy at the K-shell
      resonance peak (2.153 keV) as compared to those at below (2.146 keV) or above
      (2.160 keV) the peak. The quantum efficiency was calculated to be 2.7 x 10(-3)
      for the induction of dicentrics per photoelectric absorption of phosphorus atom
      in DNA, which was comparable to the known efficiencies of X- or gamma-ray-induced
      DNA double-strand breaks. However, comparison of the efficiencies based on the
      absorbed dose indicated that the magnitude of the enhancement was not due solely
      to the selective photoelectric absorption of the phosphorus atoms in DNA, and
      suggested the combined contributions of Auger electrons from phosphorus atoms
      within and outside the DNA molecules.

PMID- 1351529
TI  - Membrane oxidative damage induced by ionizing radiation detected by
      diphenylhexatriene fluorescence lifetime distributions.
AB  - The sensitivity of the fluorescence lifetime of 1,6-diphenyl- 1,3,5-hexatriene
      (DPH) to the dielectric constant of its environment has been used to detect
      oxidative damage to phospholipid membranes induced by ionizing radiation. The DPH
      fluorescence decay in phospholipid vesicles is described well by a continuous
      distribution of lifetime values, reflecting the various DPH depths in the bilayer
      and related to the gradient of the dielectric constant. Ionizing radiation
      oxidizes unsaturated acyl residues of phospholipids, altering the dielectric
      constant across the bilayer, sharpening the distribution of DPH lifetimes and
      increasing the centre of the distribution. Ionizing radiation doses between 22
      and 110 Gy were used, and were effective only in the presence of oxygen. A model
      based on the formation of packing defects in the bilayer describes the
      phenomenon.

PMID- 1351530
TI  - Hypoxia-specific inhibition of recovery from radiation damage by a novel 2
      nitroimidazole with a theophylline side chain.
AB  - A novel 2-nitroimidazole with a theophylline side-chain, 7-(4'-(2-nitroimidazol-1
      yl)-butyl)-theophylline, (NITP) was as efficient a hypoxic-cell radiosensitizer
      as misonidazole. However, if cells were irradiated with NITP under hypoxic
      conditions and then exposed to the drug under aerobic conditions, a much larger
      radiosensitizing effect was observed, partly because of a reduction in the size
      of the shoulder of the survival curve. There was little effect of NITP on the
      radiosensitivity of well oxygenated cells, even with post-irradiation drug
      contact. Split-dose survival curves showed that the drug inhibited recovery from
      radiation damage only when the cells were irradiated under hypoxia but not when
      irradiations were under oxic conditions. A reduction in the size of the shoulder
      of the survival curve should allow the hypoxic-cell radiosensitizing efficiency
      of NITP to be maintained with low doses of radiation used in multifraction cancer
      radiotherapy. Bifunctional drugs containing both electron-affinic and repair
      inhibiting groups may represent a new approach to the synthesis of hypoxic-cell
      targeted adjuncts to radiotherapy.

PMID- 1351531
TI  - The inherent cellular sensitivity to 62.5 MeV(p----Be+) neutrons of human cells
      differing in photon sensitivity.
AB  - The inherent sensitivity of 20 human cell lines to the 62.5 MeV(p----Be+)
      clinical neutron beam at Clatterbridge, UK, has been assessed and compared to
      their sensitivity to 4 MeV photons. The survival curves of the cell lines
      following neutron irradiation were curvilinear, and the inherent neutron
      sensitivity varied by 4.5 fold (0.1 survival level) between the extreme values,
      in the cell lines studied. There was a strong correlation between the sensitivity
      of these human cells to photon and neutron irradiation. It was concluded that
      should these in vitro patterns occur in the clinic, the 4-fold variation in RBE
      and inherent sensitivity to neutrons could result in overall lower local control
      rates following fast neutron therapy than might be anticipated. It suggests the
      need for the development of predictive assays as a potential means of selecting
      tumours most appropriate for neutron therapy.

PMID- 1351532
TI  - Inactivation of C3H 10T1/2 cells by monoenergetic high LET alpha-particles.
AB  - Inactivation of mouse C3H 10T1/2 cells in plateau-phase (7.8 x 10(4) cells/cm2)
      was studied by using alpha-particles from the irradiation facility installed for
      radiobiological experiments at the 3 MV Tandem accelerator, University of Naples.
      Silicon detectors and CR39 plastic track detectors were employed for dosimetric
      purposes. The cells were exposed to high LET monoenergetic alpha-particles
      (energy of 1.8 MeV at the centre of the cell nucleus, track-averaged LET of 177
      keV/micron and dose-rate of 1.1 Gy/min) and low-LET 80 kVp X-rays. The X-ray
      survival curve showed a significant shoulder (alpha/beta = 9 Gy) while the
      survival curve for alpha-particles was close to exponential. The mean lethal dose
      of alpha-particles was 0.77 +/- 0.02 Gy and the RBE was 5.2 at 80% survival and
      3.0 at 5% survival. Survival of exponentially growing cells (2 x 10(4) cells/cm2)
      following irradiation with the alpha-particle beam is also reported. The nuclear
      areas of 10T1/2 cells were measured as 299 +/- 9 micron 2 and 250 +/- 8 micron 2
      for cells in log phase and plateau phase, respectively. The inactivation cross
      section, obtained from the mean lethal dose, was 34 micron 2 and 37 micron 2 for
      cells in log phase and plateau phase, respectively. These values appear to be the
      maximum measured values for the inactivation cross-section of 10T1/2 cells as a
      function of the alpha-particle LET. This saturation cross-section is very similar
      to the saturation values reported in the literature for other mammalian cell
      lines.

PMID- 1351533
TI  - Strontium-90 induced bone tumours in beagle dogs: effects of route of exposure
      and dose rate.
AB  - Bone tumours from beagles exposed by inhalation to 90SrCl2 at the Inhalation
      Toxicology Research Institute (ITRI), by chronic ingestion of 90Sr at the
      Laboratory of Energy-Related Health Research (LEHR), and by injection of 90Sr
      citrate at the University of Utah were analysed to determine if the bone tumour
      characteristics differed among the three studies. The range of average skeletal
      doses at which the bone tumours occurred was similar in all three studies, but
      differences in the skeletal distribution, histological phenotype, and time to
      death were observed. The differences observed were attributed to the difference
      in dose-rate pattern obtained in the chronic ingestion study, in contrast to the
      inhalation and injection studies. In general, however, the differences noted in
      bone tumour characteristics were subtle, and would be unlikely to make an impact
      on models developed to assess the risk of human exposure to 90Sr.

PMID- 1351534
TI  - Effects of the perfluorochemical emulsion FMIQ on the radiation response of EMT6
      tumours.
AB  - The effects of FMIQ, a perfluorochemical emulsion based on perfluoro-N
      methyldecahydroisoquinoline, were examined using BALB/c mice and EMT6 mammary
      carcinomas. The radiobiological effects of FMIQ were similar to those found
      previously for Fluosol in the same tumour/host system. Although the
      perfluorochemical content (20% w/v) and oxygen-carrying capacity of FMIQ are
      similar to those of Fluosol, the formulation of FMIQ offers some advantages over
      that of Fluosol. For example, FMIQ has greater stability during storage. FMIQ
      also is formulated without pluronic F-68 and is based on a perfluorochemical
      (FMIQ) having a shorter tissue dwell time than the perfluorotripropylamine in
      Fluosol; it therefore may produce fewer side-effects than Fluosol. The lifetime
      of the circulating perfluorochemical droplets in BALB/c mice was longer than FMIQ
      than for Fluosol; this could offer an advantage in fractionated radiotherapy.
      These findings give reason to expect that FMIQ may prove to be a better emulsion
      than Fluosol for clinical use as an adjunct to cancer therapy.

PMID- 1351535
TI  - Mls: a link between immunology and retrovirology.
AB  - The nature of the mysterious minor lymphocyte stimulating (Mls) antigens has
      recently been clarified. These molecules which were key elements for our current
      understanding of immune tolerance, have a strong influence on the mouse immune
      system and are encoded by the open reading frame (orf) of endogenous and
      exogenous mouse mammary tumor viruses (MMTV's). The knowledge that these antigens
      are encoded by cancerogenic retroviruses opens an interdisciplinary approach for
      understanding the mechanisms of immune responses and immune tolerance, retroviral
      carcinogenesis, and retroviral strategies for infection.

PMID- 1351536
TI  - The HER-2/neu oncogene in breast cancer: so what is new?

PMID- 1351537
TI  - Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30
      year follow-up.
AB  - PURPOSE: To study retrospectively the long-term prognostic significance of HER-2
      oncoprotein expression in breast cancer (BC). PATIENTS AND METHODS: Two hundred
      nine consecutive female patients with invasive operable BC from a defined urban
      population were observed for a median of 30 years. Tissue expression of HER-2
      oncoprotein was demonstrated by using an immunoperoxidase procedure. RESULTS:
      Fifty-five (26%) patients had cancer and a positive HER-2 oncoprotein stain
      reaction. They had significantly worse 10- and 25-year survival rates than those
      patients who had a negative stain reaction in their cancer (31% v 48% and 31% v
      39%, respectively; P = .004). HER-2 expression was also associated with a poorer
      survival among patients who had axillary nodal metastases (P = .003; n = 104),
      but not among those patients who did not have metastases. HER-2 expression was
      related to the ductal histologic type, poor histologic grade, and high mitotic
      count, but not to tumor size, axillary nodal status, DNA ploidy, or S-phase
      fraction (SPF). In a multivariate analysis among patients with nodal metastases,
      HER-2 expression was an independent prognostic factor (P = .04) that predicted
      poor survival. However, if the entire series was entered onto the analysis, it
      did not emerge as an independent factor. CONCLUSIONS: HER-2 oncoprotein
      expression has long-term prognostic significance for predicting poor survival in
      BC, and it has an independent prognostic value among patients who presented with
      axillary nodal metastases. This result is contradictory to the argument that HER
      2 expression is only a marker for drug resistance because the patients were not
      given adjuvant drug therapy.

PMID- 1351538
TI  - Prognostic importance of c-erbB-2 expression in breast cancer. International
      (Ludwig) Breast Cancer Study Group.
AB  - PURPOSE: To evaluate the prognostic importance of immunocytochemically determined
      c-erbB-2 overexpression in the primary tumors of patients with breast cancer.
      PATIENTS AND METHODS: Primary tumors from 1,506 breast cancer patients (760 node
      negative and 746 node-positive) who were treated in the International (Ludwig)
      Breast Cancer Study Group Trial V were studied. Node-negative patients were
      allocated randomly to either a single cycle of perioperative chemotherapy (PeCT)
      or no adjuvant treatment, and node-positive patients received either a prolonged
      chemotherapy (with tamoxifen for postmenopausal patients) or a single
      perioperative cycle. RESULTS: Tumors from 16% of the node-negative patients and
      19% of the node-positive patients were found to be c-erbB-2-positive. In both
      groups c-erbB-2 positivity correlated with negative progesterone receptors (PR),
      negative estrogen receptors (ER), and high tumor grade. Lobular carcinomas were
      all negative, and, thus support the view that such tumors represent a defined
      subtype of breast carcinoma. The expression of c-erbB-2 was prognostically
      significant for node-positive but not for node-negative patients. However, in
      both subgroups, the prognostic significance was greater for patients who had
      received more adjuvant therapy. For node-positive patients, the effect of
      prolonged-duration therapy on disease-free survival (DFS) was greater for
      patients without c-erbB-2 overexpression (hazards ratio [HR], = 0.57; 95%
      confidence interval [CI], 0.46 to 0.72) than for those with c-erbB-2
      overexpression (HR, 0.77; 95% CI, 0.51 to 1.16). Similarly, for node-negative
      patients, the effect of PeCT on DFS was greater for those without c-erbB-2
      overexpression (HR, 0.82; 95% CI, 0.61 to 1.09) than for those with c-erbB-2
      overexpression (HR, 1.22; 95% CI, 0.66 to 2.25). CONCLUSION: We conclude that
      tumors with overexpression of the c-erbB-2 oncogene are less responsive to
      cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant
      therapy regimens than those with a normal amount of gene product.

PMID- 1351539
TI  - Metabotropic glutamate receptors mediate excitatory transmission in the nucleus
      of the solitary tract.
AB  - Following microinjection into the nucleus tractus solitarius (NTS), the effects
      of glutamate on the baroreceptor reflex are poorly antagonized by kynurenic acid
      and DL-2-amino-5-phosphonovaleric acid, suggesting the possible involvement of
      metabotropic glutamate receptors in this response. The metabotropic glutamate
      receptor agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD)
      depolarized neurons located medial to the tractus solitarius (TS) at the level of
      the area postrema in coronal sections of the rat NTS. This effect was mimicked by
      glutamate and was not blocked by antagonists at alpha-amino-3-hydroxy-5-methyl
      isoxazole-4-propionic acid (AMPA)/kainate or NMDA receptors. 1S,3R-ACPD also
      produced an inward current under voltage clamp that was not accompanied by a rise
      in [Ca2+]i, monitored with the Ca(2+)-sensitive dye fura-2. Conversely, the
      muscarinic agonist carbachol produced an outward current and a rise in [Ca2+]i.
      1S,3R-ACPD reduced both the excitatory and the inhibitory postsynaptic current
      resulting from single electrical stimuli in the region of the TS. High-frequency
      stimulation of the TS produced an inward current in the presence of AMPA/kainate
      and NMDA receptor blockers. This current had similar properties to that produced
      by 1S,3R-ACPD. Thus, metabotropic glutamate receptors may mediate a component of
      excitatory transmission in the NTS.

PMID- 1351540
TI  - Corticotropin-releasing factor: long-lasting facilitation of the acoustic startle
      reflex.
AB  - Intracerebroventricular infusion of corticotropin-releasing factor (CRF) (0.1-1.0
      micrograms) produced a pronounced, dose-dependent enhancement of the acoustic
      startle reflex in rats. This excitatory effect began about 20-30 min after
      infusion, grew steadily over the 2 hr test period, and lasted at least 6 hr.
      Higher doses of CRF (10 micrograms) often produced marked facilitation and then
      inhibition of startle that oscillated repeatedly with a period of 10-20 min. CRF
      enhanced startle did not result from an increase in sensitization produced by
      repetition of the startle stimulus or from a blockade of habituation. Peripheral
      injections of the autonomic ganglionic blockers hexamethonium (10 mg/kg) or
      chlorisondamine (3 mg/kg) slightly attenuated the magnitude of CRF-enhanced
      startle, suggesting a partial role of peripheral sympathetic activation.
      Intracerebroventricular infusion of the CRF antagonist alpha-helical CRF9-41
      (alpha hCRF; 25 or 50 micrograms) blocked CRF-enhanced startle when infused 5 min
      prior to CRF, indicating a central site of action. CRF-enhanced startle also was
      reversed when alpha hCRF was given 90 min after infusion of CRF. This suggests
      that exogenously applied CRF remains in the brain for a very long time after
      administration or that CRF given exogenously initiates a process that results in
      a long-lasting activation of endogenous CRF. Because the startle reflex is
      elevated by both conditioned and unconditioned fear, these data lend further
      support to the idea that CRF infusion produces a behavioral state that resembles
      fear or anxiety. Because startle is mediated by a well-defined neural pathway,
      CRF-enhanced startle may provide a useful behavioral assay to analyze the neural
      systems upon which exogenous CRF acts to produce its behavioral effects.

PMID- 1351541
TI  - Single local interneurons in the locust make central synapses with different
      properties of transmitter release on distinct postsynaptic neurons.
AB  - Quantal analysis has been applied to the inhibitory synapses made by single
      spiking local interneurons onto several nonspiking local interneurons (and
      motorneurons) in the locust CNS. Transmission at these synapses appears to be
      mediated by GABA. The apparent reversal potential of the IPSP and inhibitory
      postsynaptic current were -80 to -85 mV, a value similar to that of the potential
      evoked by pressure-applied GABA. This reversal potential was 25-30 mV more
      negative than the resting potential of the nonspiking interneurons in the
      experimental conditions. The statistical properties of release at these synapses
      were studied by recording simultaneously from pre- and postsynaptic interneurons
      with intracellular electrodes. The distribution of postsynaptic potential
      amplitudes could be described by a simple binomial model, implying uniformity of
      binomial p (probability of release at a single release site) for each synapse.
      The mean quantal amplitude was 290 +/- 110 microV, and the mean quantal content m
      of the IPSPs was 6.25 +/- 2.83. The mean values of binomial n (average size of
      the releasable pool) and p were 13.11 +/- 2.8 and 0.45 +/- 0.16, respectively.
      Numerical simulations of statistical experiments were performed to test whether
      the IPSP amplitude distribution histograms might be misleadingly indicative of
      quantal release. These simulations showed that such a hypothesis was very
      unlikely. When a spiking local interneuron was impaled, several of its target
      interneurons could sometimes be successively sampled. Quantal analysis was then
      performed with the different IPSPs evoked, in identical conditions, by a same
      presynaptic interneuron, and the quantal parameters were compared between the
      synapses. It was found that binomials n and p and their product m generally
      differed between the synapses made by a given spiking interneuron onto different
      target neurons. These results show that quantal contents can vary for the many
      synapses made centrally by one interneuron, and suggest that this variability may
      arise from differences in release probabilities between the sites associated with
      different synapses.

PMID- 1351542
TI  - Clinical implications of autonomic drugs.
AB  - Drugs that influence autonomic function are used more frequently than surgeons
      generally imagine. This article summarizes principles of autonomic pharmacology
      and highlights specific drugs that are useful to the practicing oral and
      maxillofacial surgeon.

PMID- 1351543
TI  - [Interaction between opiates and neurotransmitters/neuromodulators in spinal
      analgesia].
AB  - Systematically administered morphine produces its antinociceptive effects through
      a mechanism involving synergism of the spinal and supraspinal opiate systems.
      Descending inhibitory monoaminergic pathways, including noradrenergic and
      serotonergic descending systems, participate in this production of
      antinociception. Recent studies indicate a synergistic interaction between
      opiates and adrenergic agonists in the spinal cord. The important consideration
      arising from the apparent synergy is that significant antinociceptive effects can
      be achieved with nonspecific doses of either agonist, which alone produces only
      minimal effects. Though synergy between opiates and adrenergic drugs were
      principally considered, there remains the possibility of spinal synergistic
      interactions of opiates and other neurotransmitters/neuromodulators. Since
      decreasing the effective dosage of analgesics may lessen or eliminate the
      complications of spinal opiates or other analgesics, these combined effects will
      be extremely useful for clinical pain management.

PMID- 1351544
TI  - [Can nicardipine potentiate vecuronium induced neuromuscular blockade?].
AB  - The effects of intravenous nicardipine on the neuromuscular blockade produced by
      single bolus injection of vecuronium were studied in surgical patients undergoing
      tracheal intubation. We measured the mechanical response of the abductor pollicis
      muscle to stimulation of the ulnar nerve in a train-of-four sequence at 2 Hz and
      recorded the amplitudes of the first response (T1). Anesthesia was induced with
      thiopental 5 mg.kg-1 with or without nicardipine 10 micrograms.kg-1 followed by
      injection of vecuronium in a dose of either 0.1 or 0.15 mg.kg-1. Onset and
      duration of neuromuscular blockade were judged by percent depression of T1. The
      time intervals for 90% and 100% depression in T1 seen in patients who had
      received vecuronium 0.1 mg.kg-1 with nicardipine (n = 10) were 157.0 +/- 30.8 sec
      and 192.3 +/- 31.2 sec (mean +/- SD), respectively. These values were
      significantly shorter than those observed in patients without nicardipine
      administration (n = 10, P less than 0.05), and were not significantly different
      from the values in patients who had received vecuronium 0.15 mg.kg-1 (n = 10). On
      the other hand, the time for 25% recovery in T1 was uninfluenced by nicardipine.
      Present study indicates that nicardipine pretreatment possibly shortens the onset
      time after minor or moderate dose of vecuronium.

PMID- 1351545
TI  - [Effect of beta adrenergic blocking drugs on the prognostic value of ST-segment
      depression during exercise electrocardiogram testing].
AB  - Exercise testing has been shown to be predictive for future cardiac events in
      patients with established diagnosis of coronary heart disease. Exercise test
      parameters associated with poor prognosis may be unreliable if patient is
      receiving beta adrenergic agents. The purpose of this study was: 1) to compare
      the results of exercise testing performed before and during beta blocking
      therapy, and 2) to determine the role of beta blockers in the prognostic
      significance of the ST-segment response recorded during exercise testing. The
      study population consisted of 518 patients (mean age 52 +/- 7 years) with
      coronary heart disease. The diagnosis was based on the presence of one of the
      following three criteria: 1) typical history and significant ST-segment
      depression on resting or exercise electrocardiogram, 2) history of myocardial
      infarction, 3) significant coronary angiographic abnormalities. In all patients
      symptom-limited exercise test was performed before and two weeks after the onset
      of beta blocker therapy. The data from the first and second tests were estimated
      for significance of differences between the mean values with following results:
      maximal heart rate--135 +/- 21 and 123 +/- 19 bpm (p less than 0.001), maximal
      work load achieved--98 +/- 43 and 109 +/- 44 W (p less than 0.001), maximal
      systolic blood pressure--171 +/- 28 and 163 +/- 26 mmHg (p less than 0.001).
      Occurrence of characteristic ST-segment depression was more frequent during the
      first than during the second test (p less than 0.001).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1351546
TI  - [Cooperation between in hospital and home care, a conference of the Swiss Nursing
      Association's Office for Continuing Education. Home care services also for
      children].

PMID- 1351547
TI  - Intravenous magnesium sulphate in suspected acute myocardial infarction: results
      of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2)
AB  - The cardiovascular actions of the magnesium ion at pharmacological concentrations
      include coronary and systemic vasodilatation, platelet inhibition, and
      antiarrhythmic effects. Magnesium has also been reported to protect myocardial
      tissue in experimental models of ischaemia and reperfusion. Several small
      clinical trials in suspected acute myocardial infarction have suggested that
      early mortality can be reduced by intravenous infusion of magnesium salts in the
      acute phase, but none has been of sufficient size to be conclusive. We therefore
      conducted a randomised, double blind, placebo controlled study in 2316 patients
      with suspected acute myocardial infarction who received either intravenous
      magnesium sulphate (8 mmol over 5 min followed by 65 mmol over 24 h) or
      physiological saline. The primary outcome measure was 28-day mortality, which was
      ascertained in 99.3% of patients. The groups were well balanced for prognostic
      factors. By intention-to-treat analysis mortality from all causes was 7.8% in the
      magnesium group and 10.3% in the placebo group (2p = 0.04), a relative reduction
      of 24% (95% confidence interval 1-43%). Within the coronary care unit the
      incidence of left ventricular failure was reduced by 25% (7-39%) in the magnesium
      group (2p = 0.009). There was no significant difference between the groups in the
      incidence of heart block or the use of antiarrhythmic drugs, direct-current
      cardioversion, or temporary pacing. Myocardial infarction was confirmed in 65% of
      each group, with closely similar rises in cardiac enzymes. The side-effects of
      magnesium treatment were transient flushing, related to speed of injection of the
      loading dose, and an increased incidence of sinus bradycardia (2p = 0.02).
      Exploratory subgroup analyses of 28-day mortality did not indicate any effect
      modification by thrombolysis or aspirin, or by previous treatment with beta
      blockers, calcium antagonists, or diuretics. Intravenous magnesium sulphate is a
      simple, safe, and widely applicable treatment. Its efficacy in reducing early
      mortality of myocardial infarction is comparable to, but independent of, that of
      thrombolytic or antiplatelet therapy.

PMID- 1351548
TI  - 21-Hydroxylase, a major autoantigen in idiopathic Addison's disease.
AB  - Sera from patients with idiopathic Addison's disease commonly react with the zona
      glomerulosa of adrenal cortex. We used high-resolution western blot analysis of
      an adrenal microsomal fraction to investigate the target of these antibodies. A
      protein with an apparent molecular weight of 54 kDa was recognised as the common
      and major component. Sera identifying this autoantigen (from 12 of 16 patients)
      also showed strong immunofluorescence staining of a steroid-producing human
      adrenal adrenocortical cell line, NCI-H295. On application of antisera specific
      for different cytochrome P450 steroidogenic enzymes (side-chain cleavage enzyme,
      21-hydroxylase, 17 alpha-hydroxylase, 11 beta-hydroxylase) the mobility of the 54
      kDa protein in western blots corresponded to that of 21-hydroxylase. This
      parallel behaviour was confirmed by immunoprecipitation, electrophoresis, and
      autoradiography with the various sera and 35S-methionine-labelled NCI-H295 cell
      lysates. Preabsorptions of 35S-methionine-labelled cell lysates with the
      antiserum to 21-hydroxylase, but not with the other enzyme antisera, abolished
      precipitation of the 54 kDa autoantigen with the patient sera. These results
      indicate that 21-hydroxylase (P450c21), prominent in the zona glomerulosa of the
      adrenal cortex, is a major autoantigen in idiopathic Addison's disease.

PMID- 1351549
TI  - Serum concentrations of vitamins A and E and early outcome after ischaemic
      stroke.
AB  - Formation of free radicals and subsequent lipid peroxidation may have an
      important role in tissue injury and neuronal cell death after cerebral ischaemia.
      We conducted a prospective, controlled study to determine whether the endogenous
      antioxidant vitamins A and E had a protective function in acute ischaemic stroke.
      The study population consisted of 80 patients seen at the Free University
      Hospital in Brussels. Entry criteria were occurrence of sudden focal neurological
      deficit lasting more than 3 h; deficit due to acute ischaemia in the territory of
      the middle cerebral artery; and investigation within 24 h of onset of the
      episode. Outcome was assessed within the first 21 days. 80 controls matched for
      age and sex had various neurological disorders other than acute ischaemia. Serum
      concentrations of vitamins A and E were similar in the study and control groups.
      In the study population a serum vitamin A concentration higher than the mean of
      2.27 mumol/l was associated with a higher frequency of complete recovery within
      the first 24 h (p less than 0.05), decreased mortality (p = 0.038), and a better
      outcome as assessed by the Mathew scale of neurological deficit (p less than
      0.03) and the Barthel index. There was no significant difference in outcome
      between patients with vitamin E concentrations above or below the mean of 35.3
      mumol/l. Our results suggest a beneficial effect of a high serum vitamin A
      concentration on early outcome in ischaemic stroke.

PMID- 1351550
TI  - Anti-endothelial antibodies and coronary artery disease after cardiac
      transplantation.
AB  - Accelerated coronary artery disease is the most serious complication after
      cardiac transplantation. The disease has a multifactorial aetiology, with little
      agreement about the relative importance of the various risk factors. We have
      investigated the frequency of anti-endothelial antibodies against human umbilical
      vein endothelial cells by one-dimensional sodium dodecyl sulphate polyacrylamide
      gel electrophoresis and western blotting. Peptide-specific anti-endothelial
      antibodies were found in 15/21 heart transplant recipients with accelerated
      coronary artery disease, and 1/20 transplant patients who had not developed the
      disease. Positive immunofluorescence of patients' serum on frozen sections of
      coronary vessels confirmed the endothelial specificity of antibodies. These
      results provide evidence of an immune aetiology for transplant-associated
      coronary artery disease and could have important implications for its diagnosis
      and therapy.

PMID- 1351551
TI  - Prediction of normal-tissue tolerance to radiotherapy from in-vitro cellular
      radiation sensitivity.
AB  - The success of radiotherapy depends on the total radiation dose, which is limited
      by the tolerance of surrounding normal tissues. Since there is substantial
      variation among patients in normal-tissue radiosensitivity, we have tested the
      hypothesis that in-vitro cellular radiosensitivity is correlated with in-vitro
      normal-tissue responses. We exposed skin fibroblast cell lines from six radiation
      treated patients to various doses of radiation and measured the proportions
      surviving. There was a strong relation between fibroblast sensitivity in vitro
      and normal-tissue reactions, especially acute effects. Assessment of
      radiosensitivity could lead to improved tumour cure rates by enabling radiation
      doses to be tailored to the individual.

PMID- 1351552
TI  - Intravascular ultrasound imaging combined with coronary angioplasty.
AB  - A novel catheter combining ultrasound imaging and coronary balloon angioplasty
      was used in the treatment of 69 coronary-artery lesions in 51 patients. The
      ultrasound transducer enables real-time cross-sectional imaging and qualitative
      and quantitative assessment of the vessel wall before and after angioplasty. The
      combination catheter successfully dilated 67 lesions. There was a characteristic
      three-layered appearance, representing intima, media, and adventitia, in 60
      cases. Intravascular imaging provided information on the vessel wall unobtainable
      by standard contrast angiography in 28 cases and influenced our management in 6
      cases.

PMID- 1351553
TI  - Ear-wave to ventricular shunts.

PMID- 1351554
TI  - Zelen protocols.

PMID- 1351555
TI  - Essential trace elements and thyroid hormones.

PMID- 1351557
TI  - Purr-tenance and physiology.

PMID- 1351556
TI  - Thromboembolism during angiography.

PMID- 1351559
TI  - Intermediate-term results of heart-lung transplantation for cystic fibrosis.
AB  - Between September, 1984, and March, 1991, 79 patients underwent heart-lung
      transplantation for end-stage cystic fibrosis at the Harefield Hospital. Short
      term outcome has already been reported, and we now present intermediate-term
      results. The overall actuarial patient survival was 69% at 1 year, 52% at 2
      years, and 49% at 3 years. 17 patients had diabetes mellitus with a survival of
      62% to 1 year and 51% to 2 years. 23 patients had one or more other possible high
      risk factors, and survival of these patients was 64% at 1 year and 57% at 2
      years, compared with 71% and 49%, respectively, in the low-risk group (n = 56).
      Pseudomonas aeruginosa infection was the most common respiratory infection
      encountered postoperatively. 92% of patients had at least one episode of acute
      rejection during the first 3 postoperative months. Lung function was greatly
      improved after transplantation, the mean forced expiratory volume in 1 s and
      forced vital capacity increasing from 22% and 35% predicted, respectively,
      preoperatively to 68% and 70% predicted, respectively, by the sixth postoperative
      month. This improvement was maintained at 1, 2, and 3 years after
      transplantation. Lymphoproliferative disorders (4 patients) were successfully
      treated. Obliterative bronchiolitis developed in 17 patients and the cumulative
      probability of getting this complication at 1, 2, and 3 years postoperatively was
      17%, 23%, and 48%, respectively. Overall, 7 patients were retransplanted. There
      was no coronary artery disease in the 37 patients who underwent coronary
      angiography at 1 year, 14 at 2 years, and 9 at 3 years after surgery. 58 patients
      donated their hearts for subsequent "domino" heart transplantation. Our 5 1/2
      year experience with heart-lung transplantation is encouraging but the shortage
      of donor organs and the complication of obliterative bronchiolitis are the two
      main obstacles to be overcome.

PMID- 1351558
TI  - Cell migration, chimerism, and graft acceptance.

PMID- 1351560
TI  - Health effects of white-water canoeing.
AB  - There is little quantitative information on the relation between water quality
      and disease attack rates after recreational activities in fresh water. We
      conducted a prospective cohort study to measure the health effects of white-water
      and slalom canoeing in two channels with different degrees of microbial
      contamination. Site A, fed by a lowland river, showed high enterovirus
      concentrations (arithmetic mean 198 pfu per 10 litre and moderate faecal coliform
      concentrations (geometric mean 285/dl); at site B, from an upland impoundment,
      all samples were free of enteroviruses and the geometric mean faecal coliform
      concentration was 22/dl. Between 5 and 7 days after exposure canoeists using site
      A had significantly higher incidences of gastrointestinal and upper respiratory
      symptoms than canoeists using site B or non-exposed controls (spectators). Like
      seawater bathers, fresh-water canoeists can be made ill by sewage contamination.
      The hazard of fresh water may be best measured by counting of viruses rather than
      bacteria.

PMID- 1351562
TI  - The Gallo case: is this really happening?

PMID- 1351561
TI  - Indian medical journals.
AB  - Although Indian doctors produce half the articles published from the third world,
      little has been written about Indian medical journals. We examined 75 of the 113
      serious English-language journals published in India. Of the 22 included in the
      Cumulated Index Medicus only 8 were judged by Indian and foreign referees to be
      of international standard. A survey of Indian authors indicated that foreign
      journals were chosen for the best papers because of their wider circulation,
      better refereeing practices, and punctuality. More than 98% of medical articles
      from India probably go unnoticed by the international medical community.

PMID- 1351563
TI  - Death of child with supraventricular tachycardia.

PMID- 1351564
TI  - Desferrioxamine in acute iron poisoning.

PMID- 1351565
TI  - Desferrioxamine in acute iron poisoning.

PMID- 1351566
TI  - Desferrioxamine in acute iron poisoning.

PMID- 1351567
TI  - Desferrioxamine in acute iron poisoning.

PMID- 1351568
TI  - Desferrioxamine in acute iron poisoning.

PMID- 1351569
TI  - Mode of delivery in HIV-1-infected women.

PMID- 1351570
TI  - Glutathione deficiency and HIV infection.

PMID- 1351571
TI  - T cells, V genes, and HIV.

PMID- 1351572
TI  - Failure to detect human papillomavirus in Kaposi's sarcoma.

PMID- 1351573
TI  - Lack of suppression by ribavirin of HIV viraemia.

PMID- 1351574
TI  - Increasing penicillin resistance in pneumococci in Iceland.

PMID- 1351575
TI  - Contamination of immunoassay controls with hepatitis C virus.

PMID- 1351576
TI  - Detection of antibodies to hepatitis C virus in urine.

PMID- 1351577
TI  - Carbon-adsorbed mitomycin prophylaxis against recurrence of gastric cancer.

PMID- 1351578
TI  - Latex dummies as allergens.

PMID- 1351579
TI  - Laparoscopic pericardial fenestration for malignant pericardial effusion.

PMID- 1351580
TI  - Latex allergy and repeated graft rejections.

PMID- 1351581
TI  - Donor dendritic cell repopulation in recipients after rat-to-mouse bone-marrow
      transplantation.

PMID- 1351582
TI  - Antimyeloperoxidase antibodies and adverse reactions to clozapine.

PMID- 1351583
TI  - Main graft vessels thromboses due to conventional-dose OKT3 in renal
      transplantation.

PMID- 1351584
TI  - Purity of factor VIII concentrates.

PMID- 1351585
TI  - Guidelines for doctors in North America.

PMID- 1351586
TI  - Keeping up with the journals.

PMID- 1351587
TI  - Smoking in the workplace.

PMID- 1351588
TI  - Children with genetic diseases: who should pay?

PMID- 1351589
TI  - Acute weight reduction in junior doctors.

PMID- 1351590
TI  - Compensation for medically acquired AIDS.

PMID- 1351591
TI  - Safety guidelines for use of nitric oxide.

PMID- 1351592
TI  - Acute-phase response in patients given rhIL-3 after chemotherapy.

PMID- 1351593
TI  - Acute-phase response in patients given rhIL-3 after chemotherapy.

PMID- 1351594
TI  - Human growth hormone and restoration of hypoglycaemia awareness.

PMID- 1351595
TI  - Human growth hormone and restoration of hypoglycaemia awareness.

PMID- 1351596
TI  - Insulin-like growth factor I stimulates bone turnover in osteoporosis.

PMID- 1351597
TI  - Insulin resistance and cigarette smoking.

PMID- 1351598
TI  - Decrease of serum Clara cell protein in smokers.

PMID- 1351599
TI  - Leukaemia incidence after iodine-131 exposure.
AB  - Leukaemia is one of the most prominent late effects of exposure to ionising
      radiation. We have studied the incidence of leukaemia among 46,988 Swedish
      patients exposed to iodine-131 (131I) for diagnostic reasons or to treat
      hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared
      with that expected based on incidence data from the general population. The mean
      absorbed dose to the bone marrow was estimated as 14 mGy (range 0.01-2.226). 195
      leukaemias occurred more than 2 years after exposure, and the standardised
      incidence ratio (SIR) was 1.09 (95% confidence interval 0.94-1.25). Similar, but
      again not significantly, increased risks were seen for chronic lymphocytic
      leukaemia (CLL) (SIR = 1.08), a malignant condition not found to be increased
      after irradiation, and for non-CLL (SIR = 1.09). The risk of leukaemia did not
      vary by sex, age, time, or radiation dose from 131I. One reason for the absence
      of a radiation effect, other than chance, includes the possible lowering of risk
      when exposure is protracted over time as occurs with 131I. Excess leukaemia risks
      of more than 25% could thus be excluded with high assurance in this population of
      mainly adults. These results should be reassuring to patients exposed to 131I in
      medical practice and to most individuals exposed to the fall-out from the
      Chernobyl accident.

PMID- 1351600
TI  - Efficacy of traditional Chinese herbal therapy in adult atopic dermatitis.
AB  - There has been considerable interest in traditional Chinese herbal therapy (TCHT)
      as a new treatment for atopic dermatitis. To establish the efficacy and safety of
      this treatment, a daily decoction of a formula containing ten herbs that has been
      found to be beneficial in open studies was tested in a double-blind placebo
      controlled study. 40 adult patients with longstanding, refractory, widespread,
      atopic dermatitis were randomised into two groups to receive 2 months' treatment
      of either the active formulation of herbs (TCHT) or placebo herbs, followed by a
      crossover to the other treatment after a 4-week washout period. The main outcome
      measures were extent and severity of erythema and surface damage as judged by
      standardised body scores. The patients' own assessments of the overall response
      to treatment were also sought. The geometric mean score for erythema at the end
      of active treatment was 12.6 (95% confidence interval [CI] 5.9 to 22.0) and at
      the end of the placebo phase was 113 (65 to 180). The geometric mean score for
      surface damage was 11.3 (5.8 to 21.8) and 111.0 (68 to 182), respectively. The
      95% CI for the mean geometric ratio for the two values with active treatment was
      0.04 to 0.22 for erythema (p less than 0.0005) and 0.04 to 0.27 for surface
      damage (p less than 0.0005). Of the 31 patients who completed the study and
      expressed a preference, 20 preferred that phase of the trial in which they
      received TCHT whereas 4 patients preferred placebo (p less than 0.02). There was
      a subjective improvement in itching (p less than 0.001) and sleep (p less than
      0.078) during the TCHT treatment phase. No side-effects were reported by the
      patients although many commented on the unpalatability of the decoction. TCHT
      seems to benefit patients with atopic dermatitis. Palatability of the treatment
      needs to be improved and its safety assured.

PMID- 1351601
TI  - Pregnancies after intracytoplasmic injection of single spermatozoon into an
      oocyte.
AB  - Intracytoplasmic sperm injection (ICSI) is a promising assisted-fertilisation
      technique that may benefit women who have not become pregnant by in-vitro
      fertilisation (IVF) or subzonal insemination (SUZI) of oocytes. We have used ICSI
      to treat couples with infertility because of severely impaired sperm
      characteristics, and in whom IVF and SUZI had failed. Direct injection of a
      single spermatozoon into the ooplasm was done in 47 metaphase-II oocytes: 38
      oocytes remained intact after injection, 31 became fertilised, and 15 embryos
      were replaced in utero. Four pregnancies occurred after eight treatment cycles-
      two singleton and one twin pregnancy, and a preclinical abortion. Two healthy
      boys have been delivered from the singleton pregnancies and a healthy boy and
      girl from the twin pregnancy.

PMID- 1351602
TI  - Young and unfit?

PMID- 1351603
TI  - Of cabbages and chlorine: cholera in Peru.

PMID- 1351604
TI  - Thrombolysis for pulmonary embolism.

PMID- 1351605
TI  - Noonan's syndrome.

PMID- 1351606
TI  - Outpatients on tape.

PMID- 1351607
TI  - "Friendly fire" in medicine: hormones, homografts, and Creutzfeldt-Jakob disease.

PMID- 1351608
TI  - Waterborne transmission of epidemic cholera in Trujillo, Peru: lessons for a
      continent at risk.
AB  - The epidemic of cholera that began in Peru in January, 1991, marked the first
      such epidemic in South America this century. Subsequently, over 533,000 cases and
      4700 deaths have been reported from nineteen countries in that hemisphere. We
      investigated the epidemic in Trujillo, the second largest city in Peru.
      Trujillo's water supply was unchlorinated and water contamination was common.
      Suspect cholera cases were defined as persons presenting to a health facility
      with acute diarrhoea between Feb 1, and March 31, 1991. We studied a cohort of
      150 patients who had been admitted to hospital and conducted a matched case
      control study with 46 cases and 65 symptom-free and serologically uninfected
      controls; we also carried out a water quality study. By March 31, 1991, 16,400
      cases of suspected cholera (attack rate 2.6%), 6673 hospital admissions, and 71
      deaths (case-fatality rate 0.4%) had been reported in the province of Trujillo.
      79% of stool cultures of patients with diarrhoea presenting to a single hospital
      yielded Vibrio cholerae O1. In the case-control study, drinking unboiled water
      (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.3-7.3), drinking water from
      a household water storage container in which hands had been introduced into the
      water (4.2, 1.2-14.9), and going to a fiesta (social event) (3.6, 1.1-11.1) were
      associated with illness. The water quality study showed progressive contamination
      during distribution and storage in the home: faecal coliform counts were highest
      in water from household storage containers and lowest in city well water. V
      cholerae O1, biotype El Tor, serotype Inaba, was isolated from three city water
      samples. Cholera control measures in Trujillo should focus on treatment of water
      and prevention of contamination during distribution and in the home. Trujillo's
      water and sanitation problems are common in South America; similar control
      measures are needed throughout the continent to prevent spread of epidemic
      cholera.

PMID- 1351609
TI  - Evaluation of endoscopy for early detection of gastric-stump cancer.
AB  - The value of endoscopic surveillance of postgastrectomy patients for the early
      detection of gastric-stump cancer is controversial. Using data from an Amsterdam
      postgastrectomy cohort of 2633 patients, we have done a retrospective analysis of
      the effect on mortality from gastric cancer of endoscopic surveillance in these
      patients. Between 1976 and 1982, 504 symptom-free patients from the Amsterdam
      cohort participated in an endoscopic surveillance programme. All patients were
      followed up until 1988. Relative to the general Dutch population, risk of death
      from gastric cancer was less among patients who took part in surveillance than
      among those who did not participate. However, differences were small and similar
      differences existed for risk of death from lung and colorectal cancers,
      suggesting the presence of selection. Our study seems to confirm that large-scale
      surveillance of postgastrectomy patients is not justified.

PMID- 1351610
TI  - Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von
      Willebrand's disease the link?
AB  - An association between aortic stenosis and haemorrhage from gastrointestinal
      angiodysplasia has been recognised for many years, but no explanation for this
      link has been found. Remarkably, aortic valve replacement, rather than bowel
      resection, corrects the bleeding. Aortic stenosis can be complicated by acquired
      von Willebrand's disease type IIA (vWD-IIA), which is corrected after valve
      replacement, and gastrointestinal angiodysplasia is a common site of bleeding in
      older patients with acquired or congenital vWD. Could the stenotic aortic valve
      lead to an acquired, reversible deficiency of the largest multimers of plasma von
      Willebrand factor (equivalent to vWD-IIA) and thus explain the association with
      gastrointestinal haemorrhage?

PMID- 1351611
TI  - Exitus auditus--no fun.

PMID- 1351612
TI  - Undue burden of abortion.

PMID- 1351613
TI  - DMPA, zalcitabine, and the FDA.

PMID- 1351614
TI  - Decline in 5-year survival rates for cancer of head and neck.

PMID- 1351615
TI  - Coronary atheroma regression trials.

PMID- 1351616
TI  - Prurigo nodularis and aluminium overload in maintenance haemodialysis.

PMID- 1351617
TI  - Topical retinoids for warts and keratoses in transplant recipients.

PMID- 1351618
TI  - Radiation recall induced by tamoxifen.

PMID- 1351620
TI  - Double-blind study of selective decontamination of the digestive tract in
      intensive care.
AB  - Selective decontamination of the digestive tract (SDD), by means of non
      absorbable antibiotics, to prevent infection in intensive-care units (ICUs)
      remains controversial; there is evidence that the regimen reduces the incidence
      of secondary infection, but no convincing reduction in morbidity or mortality has
      been shown and the costs and effect on microbial resistance patterns need further
      study. In a double-blind, placebo-controlled trial, we have tried to find out
      whether SDD should be used routinely in all ICU patients at high risk of
      secondary infection. All patients admitted to the ICU who were thought likely to
      stay in the unit for at least 5 days and to need intubation for longer than 48 h
      were enrolled and randomly allocated to groups receiving placebo or SDD
      (amphotericin, colistin, and tobramycin applied to the oropharynx and enterally);
      all patients received intravenous cefotaxime for 72 h. Of 322 patients
      randomised, 83 were withdrawn (80 ICU stay or duration of intubation too short, 3
      protocol violations). 239 medical, trauma, and surgical patients completed the
      trial period (114 SDD, 125 placebo). There were no differences between SDD and
      placebo groups in incidence of infection (30 [26%] vs 43 [34%] patients; p =
      0.22), duration of ICU stay (mean 16.2 [14.3] vs 16.8 [12.3] days), hospital stay
      (29.9 [SD 25.0] vs 31.9 [22.2] days), or mortality (21 [18%] vs 21 [17%]). SDD
      substantially increased the costs of intensive care. Mechanisms other than
      bacterial colonisation of the gut may bring about substantial numbers of
      secondary infections in ICUs. Routine use of SDD in multidisciplinary ICUs cannot
      be recommended.

PMID- 1351621
TI  - Penicillin-resistant pneumococcal meningitis.

PMID- 1351619
TI  - Penicillin-resistant pneumococcal meningitis.

PMID- 1351622
TI  - Violent death and cholesterol reduction.

PMID- 1351623
TI  - Serological tests to monitor treatment of Helicobacter pylori.

PMID- 1351624
TI  - Serological tests to monitor treatment of Helicobacter pylori.

PMID- 1351625
TI  - HLA-DQB1*03 and cervical intraepithelial neoplasia type III.

PMID- 1351626
TI  - Mycobacterial aetiology of sarcoidosis.

PMID- 1351627
TI  - Dextromethorphan and parkinsonism.

PMID- 1351628
TI  - Tissue polypeptide antigen and pre-eclampsia.

PMID- 1351629
TI  - Psychosocial stress and severe prematurity.

PMID- 1351630
TI  - Lack of association between type 1 diabetes and the glucokinase gene.

PMID- 1351632
TI  - Euthanasia.

PMID- 1351631
TI  - Aspirin-ticlopidin in Kasabach-Merritt syndrome.

PMID- 1351633
TI  - Euthanasia.

PMID- 1351634
TI  - Surgical careers and female doctors.

PMID- 1351635
TI  - Surgical careers and female doctors.

PMID- 1351636
TI  - Blood donation.

PMID- 1351637
TI  - EC oral snuff ban and Sweden.

PMID- 1351638
TI  - Safer sex and women in Africa.

PMID- 1351639
TI  - AIDS in India.

PMID- 1351640
TI  - Origins of HIV.

PMID- 1351641
TI  - Peripartum HIV seroconversion: a cautionary tale.

PMID- 1351642
TI  - Transmission of HIV-1 from seronegative but PCR-positive blood donor.

PMID- 1351643
TI  - Betel nut chewing and asthma.

PMID- 1351645
TI  - Acetic acid to treat Pseudomonas aeruginosa in superficial wounds and burns.

PMID- 1351644
TI  - Guillain-Barre syndrome and ganglioside therapy in Italy.

PMID- 1351646
TI  - Migraine.

PMID- 1351647
TI  - Migraine.

PMID- 1351648
TI  - Migraine.

PMID- 1351649
TI  - Migraine.

PMID- 1351650
TI  - Migraine.

PMID- 1351651
TI  - Fibrinogen genes and peripheral arterial disease.

PMID- 1351652
TI  - Neutralising antibodies against C3NeF in intravenous immunoglobulin.

PMID- 1351653
TI  - Pralidoxime for organophosphorus poisoning.

PMID- 1351655
TI  - [Fatigue, tiredness and weakness].

PMID- 1351654
TI  - Long-term thyroxine treatment and bone mineral density.
AB  - Studies of the effect of thyroxine replacement therapy on bone mineral density
      have given conflicting results; the reductions in bone mass reported by some have
      prompted recommendations that prescribed doses of thyroxine should be reduced. We
      have examined the effect of long-term thyroxine treatment in a large homogeneous
      group of patients; all had undergone thyroidectomy for differentiated thyroid
      cancer but had no history of other thyroid disorders. The 49 patients were
      matched with controls for age, sex, menopausal status, body mass index, smoking
      history, and calcium intake score; in all subjects bone mineral density at
      several femoral and vertebral sites was measured by dual-energy X-ray
      absorptiometry. Despite long-term thyroxine therapy (mean duration 7.9 [range 1
      19] years) at doses (mean 191 [SD 50] micrograms/day) that resulted in higher
      serum thyroxine and lower serum thyrotropin concentrations than in the controls,
      the patients showed no evidence of lower bone mineral density than the controls
      at any site. Nor was bone mineral density correlated with dose, duration of
      therapy, or cumulative intake, or with tests of thyroid function. There was a
      decrease in bone density with age in both groups. We suggest that thyroxine alone
      does not have a significant effect on bone mineral density and hence on risk of
      osteoporotic fractures.

PMID- 1351656
TI  - Neuroendocrine carcinoma in a patient with hairy cell leukemia: a case report.
AB  - Second malignancies are common in hairy cell leukemia. We report a case of a
      neuroendocrine carcinoma arising in a patient who had been diagnosed with hairy
      cell leukemia 6 years earlier. This case is the first report of these two tumors'
      occurring together. The pathogenetic basis for the presence of these two uncommon
      tumors in our patient is discussed.

PMID- 1351657
TI  - Ammonia-induced alterations in the metabolism of glutamate and aspartate in
      neuronal perikarya and synaptosomes of rat cerebellum.
AB  - The effect of subacute and acute doses of ammonium acetate was studied on the
      production of 14CO2 from 14C-labeled glutamate and aspartate by neuronal
      perikarya and synaptosomes isolated from rat cerebellum. Studies with inhibitors
      for aminotransferases (aminooxy acetic acid) and glutamate dehydrogenase
      (glutamic acid diethyl ester) indicated that transamination reactions play a
      major role in this process. There was a suppression in this process in
      hyperammonemic states. Activities of the enzymes, aspartate aminotransferase,
      alanine aminotransferase, glutamate dehydrogenase and glutaminase were decreased
      in both preparations in hyperammonemic states. Activity of glutamine synthetase
      was unaltered.

PMID- 1351658
TI  - Ovarian cancer--unrealistic expectations.

PMID- 1351659
TI  - ATP mediates fast synaptic transmission in mammalian neurons.
AB  - In addition to its diverse functions inside cells, ATP can act at several types
      of cell-surface receptor. One of these (P2X-purinoceptor) is believed to be a
      ligand-gated cation channel. The presence of P2X receptors on autonomic, sensory
      and central neurons suggests that ATP might be released to act as a fast
      excitatory synaptic transmitter. Here we record excitatory synaptic potentials
      and currents from cultured coeliac ganglion neurons which are mimicked by ATP,
      blocked by the P2-purinoceptor antagonist suramin, desensitized by alpha,beta
      methylene-ATP and unaffected by antagonists acting at nicotine, 5
      hydroxytryptamine, N-methyl-D-aspartate (NMDA), non-NMDA glutamate, gamma
      aminobutyric acid (GABA), noradrenaline or adenosine receptors. We conclude that
      ATP is the neurotransmitter at this neuroneuronal synapse.

PMID- 1351660
TI  - [Clinically non-functioning hypophyseal adenomas; diagnostic possibilities and
      therapeutic options].

PMID- 1351661
TI  - [Coma due to overdose of valnoctamide].

PMID- 1351662
TI  - Modulation of glutamate agonist-induced influx of calcium into neurons by gamma-L
      glutamyl and beta-L-aspartyl dipeptides.
AB  - Gamma-L-Glutamate and beta-L-aspartate dipeptides, present in the mammalian brain
      with a yet unknown function, were shown to affect the influx of Ca2+ into
      cultured cerebellar granule cells. The most active peptides, gamma-L-glutamyl-L
      aspartate, gamma-L-glutamyl-L-glutamate and gamma-L-glutamylglycine, enhanced the
      basal influx but inhibited the glutamate-activated influx of Ca2+ in a dose
      dependent manner. Gamma-L-Glutamyl-L-aspartate, the strongest inhibitor of the
      glutamate-activated influx of Ca2+, exhibited selective Mg(2+)-dependent
      antagonism in the N-methyl-D-aspartate (NMDA)-activated influx of Ca2+. This
      finding may explain its previously shown deleterious effects on the long-term
      memory. On the other hand, gamma-L-glutamyl-L-aspartate enhanced alone the entry
      of Ca2+ into neurons. This effect was antagonized by the non-NMDA antagonists 6
      nitro-7-cyanoquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione
      (DNQX), suggesting a non-NMDA receptor-mediated action, that may also be involved
      in excitotoxicity in some neurodegenerative disorders.

PMID- 1351663
TI  - L-homocysteic acid selectively activates N-methyl-D-aspartate receptors of rat
      retinal ganglion cells.
AB  - To explore the possible role of L-homocysteic acid (HCA) as a retinal
      transmitter, whole-cell recordings with patch electrodes were performed on
      isolated rat retinal ganglion cells (RGCs) in culture. HCA elicited an inward
      current at -60 mV. Similar to currents evoked at this potential in RGCs by N
      methyl-D-aspartate (NMDA), HCA-activated currents were of relatively small
      amplitude (10-150 pA), and the noise level increased dramatically during the
      response. When HCA was co-applied with concentrations of NMDA that elicited a
      maximal response, the current was not increased over that of NMDA alone. HCA
      evoked currents were almost completely blocked by the NMDA antagonists D-2-amino
      5-phosphonovalerate (D-AP5), Mg2+, or 7-chlorokynurenate (7-Cl KYN). Unlike its
      effects on other preparations, even millimolar concentrations of HCA did not
      activate kainate-like currents. These observations suggest that HCA specifically
      activates the NMDA receptor-channel complex of rat RGCs.

PMID- 1351664
TI  - The neuroprotective effects of dextromethorphan on guinea pig-derived hippocampal
      slices during hypoxia.
AB  - The purpose of this study was to determine whether dextromethorphan, an opioid
      class antitussive, prevents hypoxia-induced loss of nerve function in an in vitro
      hippocampal slice preparation. The evoked population spike (PS) was recorded from
      CA1 pyramidal cells of guinea pig-derived hippocampal slices. Hippocampal slices
      were superfused with O2 (95%)/CO2 (5%) gassed artificial cerebral spinal fluid
      (ACSF) at 37 degrees C. The PS did not recover during reoxygenation in slices
      that were made hypoxic for 30 min by exposure to N2 (95%)/CO2 (5%) gassed ACSF in
      place of oxygenated ACSF. The PS recovered during reoxygenation, following 30 min
      of hypoxia, in 9 of 10 slices treated with dextromethorphan (100 microM) and in 4
      of 6 slices treated with D,L-2-amino-5-phosphono-valerate (AP-5) (100 microM), an
      NMDA receptor antagonist. The mean PS amplitudes, one hour after perfusion with
      oxygenated ACSF, were 42% and 51%, respectively, of the pre-hypoxia amplitude.
      The PS recovered during reoxygenation in all of seven slices superfused with
      lowered temperature ACSF (25 degrees C) during 30 min of hypoxia. The results
      show that dextromethorphan, like the NMDA antagonist AP-5 and lowered
      temperature, protected neurons from hypoxia-induced injury in the hippocampus.

PMID- 1351665
TI  - A muscle-derived factor antagonizes the neurotoxicity of glutamate in dissociated
      cell cultures of chick telencephalic neurons.
AB  - Excitatory amino acids including glutamate are known to reveal considerable
      neurotoxicity in various nervous systems. Our previous studies revealed that the
      chick muscle extract contains a factor which promotes the survival of
      telencephalic neurons. Further investigations clearly showed that this extract
      contains the factor that antagonizes the neurotoxicity of glutamate in a
      dissociated telencephalic neuronal culture system optimized for detection of the
      toxicity. This factor reduced at least the toxicity mediated by non-N-methyl-D
      aspartate (non-NMDA) receptor.

PMID- 1351666
TI  - Effects of somatostatin on potassium currents in bullfrog sympathetic ganglion
      neurones: possible role of receptor subtypes.
AB  - The effects of whole somatostatin (wSS; somatostatin-28) and cyclic somatostatin
      (cSS; somatostatin-14) were examined on patch-clamped bullfrog sympathetic
      ganglion neurones. In the C-cells, where muscarine produces hyperpolarization,
      wSS was also inhibitory and activated an inwardly-rectifying K+ current; cSS was
      ineffective. By contrast, in the B-cells, where muscarine produces excitatory
      effects, cSS was also excitatory and was more effective than wSS in suppressing a
      voltage-dependent, non-inactivating K(+)-current (IM). These results are
      consistant with the idea that excitatory and inhibitory effects of somatostatin
      derived peptides may be mediated via different receptor subtypes.

PMID- 1351667
TI  - Vagal stimulation and somatostatin potentiate cardiac vagal action in the toad,
      Bufo marinus.
AB  - Cholinergic postganglionic neurones of the cardiac vagus in the toad, Bufo
      marinus, have been shown to contain the peptide somatostatin (SOM), which causes
      direct negative inotropic and chronotropic effects on the heart. In anaesthetised
      toads, high frequency stimulation (10 Hz) of cardiac vagus nerves results in
      prolonged cardiac slowing and potentiation of the cardiac slowing measured in
      response to a train of vagal stimuli at low frequency. Intravenous administration
      of the tetradecapeptide form of SOM also results in prolonged cardiac slowing and
      potentiation of cardiac vagal action. Effects on heart rate of small bolus doses
      of acetylcholine (ACh) were unaltered by administration of SOM, at the same time
      as cardiac vagal slowing was enhanced. It is suggested that SOM is released from
      vagal nerve endings by high frequency stimulation and enhances cardiac vagal
      action by a presynaptic mechanism.

PMID- 1351668
TI  - Role of N-methyl-D-aspartate and opiate receptors in nociception during and after
      ischaemia in rats.
AB  - We have investigated the effects of systemic administration of two N-methyl-D
      aspartate (NMDA) receptor antagonists and two opiate agonists on nociception
      during and after tail ischaemia in conscious rats. The two NMDA receptor
      antagonists, D-2-amino-5-phosphonovalerate (APV) and ketamine hydrochloride, did
      not alter tail flick latencies in rats not subjected to ischaemia but inhibited
      post-ischaemic hyperalgesia (PIH) in a dose-dependent manner. Neither of these
      agents impaired motor function of the rats, as assessed by rotarod performance,
      suggesting a purely sensory antinociceptive effect. The antinociceptive effect of
      APV during reperfusion following ischaemia was not antagonised by the mu-opiate
      receptor antagonist naloxone (1 mg/kg). The two opiate receptor agonists,
      morphine and pethidine, increased tail flick latencies in rats not subjected to
      ischaemia, inhibited PIH in a dose-dependent manner, and also caused significant
      motor malfunction, all in naloxone-reversible fashion. We conclude that the role
      of the NMDA receptor in mediating afferent nociceptive traffic is confined to its
      involvement in neuronal events mediating hyperalgesia.

PMID- 1351669
TI  - [Prenatal diagnosis of mucoviscidosis: indication of enzyme determination and
      molecular biology techniques].
AB  - Prenatal diagnosis of cystic fibrosis established by study of RFLPs flanking the
      gene and, since 1989, by direct detection of the major mutation delta F508 is now
      widely used. However, there are still some indications of prenatal diagnosis by
      microvillar intestinal enzymes analysis. We propose a prenatal diagnosis strategy
      which combines both methods. This diagnosis strategy is applied to families with
      a 1/4 to 1/200 risk. Screening of delta F508 in the general population is
      discussed.

PMID- 1351670
TI  - Drug interaction with alcohol and environmental chemicals.

PMID- 1351671
TI  - [Amalgam war on a high level].

PMID- 1351672
TI  - Effect of microcapsules of luteinizing hormone-releasing hormone antagonist SB-75
      and somatostatin analog RC-160 on endocrine status and tumor growth in the
      Dunning R-3327H rat prostate cancer model.
AB  - Inhibitory effects of sustained delivery systems (microcapsules) of the modern
      antagonist of luteinizing hormone-releasing hormone [Ac-D-Nal(2)1, D-Phe(4Cl)2, D
      Pal(3)3, D-Cit6, D-Ala10]LH-RH (SB-75) or the potent somatostatin analog D-Phe
      Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) were investigated in the Dunning R
      3327H rat prostate cancer model. In the first experiment, the treatment was
      started 4 months after tumor transplantation, when the tumors measured
      approximately 2 cm3. Tumor volumes and weights were significantly reduced by SB
      75 microcapsules releasing 48 micrograms/day or RC-160 microcapsules releasing 38
      micrograms/day given alone, as compared with the control. The combination of
      these two analogs showed a synergistic effect. In the second experiment, the
      treatment was started 7 months after tumor transplantation, when the tumors were
      well developed and measured about 16 cm3. In addition to a significant reduction
      in volume, weight, and growth rate of tumors, histological signs of tumor
      regression were found in the groups treated with SB-75 microcapsules releasing 72
      micrograms/day given alone or in combination with RC-160 microcapsules releasing
      76 micrograms/day, but not with RC-160 alone. No synergistic effect of the
      combination therapy was found in the second experiment. Serum testosterone levels
      decreased to undetectable levels and LH levels were also diminished within 2
      weeks by administration of SB-75 alone or in combination with RC-160. In both
      experiments, the weights of testes, ventral prostate, and seminal vesicles were
      greatly reduced by administration of SB-75 alone or in combination with RC-160.
      Our results suggest that the combined therapy with microcapsules of SB-75 and RC
      160, started soon after the diagnosis of prostate cancer is made, could improve
      therapeutic response.

PMID- 1351674
TI  - Brain concentrations of white spirit components and neurotransmitters following a
      three week inhalation exposure of rats.

PMID- 1351673
TI  - Caffeine moderately antagonizes the effects of triazolam and zopiclone on the
      psychomotor performance of healthy subjects.
AB  - To determine whether caffeine antagonizes the decremental effects of triazolam
      and zopiclone on human performance, oral single doses of 0.250 mg triazolam, 7.5
      mg zopiclone, or respective placebos, with and without 300 mg caffeine, were
      given to parallel groups of student volunteers in two double-blind studies.
      Objective tests and subjective visual analogue ratings were done at baseline and
      30 min. and 90 min. after the intake. In Study I, triazolam produced drowsiness
      at 30 min. but did not differ from the placebo in other tests. Caffeine induced
      alerting effects in various tests and differed from triazolam in some (digit
      substitution, drowsiness, calmness, mental slowness) but not all variables
      measured. Caffeine and triazolam were interpreted as being antagonists. In Study
      II, zopiclone impaired digit substitution and flicker fusion, produced exophoria
      and lowered systolic blood pressure. Caffeine differed from zopiclone in several
      test functions, but it also differed from caffeine + zopiclone whereas zopiclone
      differed from caffeine + zopiclone only in two tests (Maddox wing, systolic blood
      pressure). Thus, zopiclone counteracted the effects of caffeine more easily than
      caffeine counteracted the decremental effects of zopiclone. We conclude that
      triazolam may not differ importantly from diazepam as regards their antagonism
      towards caffeine, whereas further research on the antagonism between zopiclone
      and caffeine needs to be done.

PMID- 1351675
TI  - [Cancer of the pancreas. A plea for resection. 162 operated patients].
AB  - Between 1970 and 1990, 162 patients with carcinoma of the pancreas or the
      periampullary region were operated upon. A prospective study was conducted in 85
      of them who underwent surgery after 1983. The tumour was resected in 63 patients
      (ductal adenocarcinoma in 43, periampullary carcinoma in 20). Biliary and/or
      gastrointestinal bypass was performed in 76 patients, and exploratory laparotomy
      in 23. The operative mortality rate was 3 percent (2/63) among patients with
      resection and 24 percent (24/99) among those with laparotomy with or without
      bypass. The longest survival (median: 33 months) was obtained in patients with
      periampullary tumours; it was 12 months after resection in patients with ductal
      adenocarcinoma and 4 months in the other cases. The preoperative estimate of
      unresectability was erroneous in 36.5 percent of the cases. Periampullary tumours
      were diagnosed only after pathological examination of the lesion removed in 47
      percent. These results are in favour of radical surgery, especially since the
      operative mortality of resection is low and since resection, even palliative,
      gives a better survival rate than mere bypass.

PMID- 1351676
TI  - [Takayasu's disease. Exploration by intra-arterial digital angiography. 50
      cases].
AB  - The long-term prognosis of Takayasu's disease depends on an elective surgical
      treatment which requires full and accurate assessment of the lesions. We present
      here a retrospective study of 50 patients explored before surgery by intra
      arterial digital angiography. In 92 percent of the patients the thoraco-abdominal
      aorta and its branches were well documented on 2 orthogonal projections performed
      in one single session. The high-quality intra-arterial opacification made it
      possible to detect incipient parietal lesions and to evaluate the lesions of the
      small caliber branches and the downstream bed in case of occlusion. These
      advantages, and the absence of morbidity in our experience, make digital
      panarteriography a method of choice to evaluate Takayasu's disease.

PMID- 1351677
TI  - Studies of the cloned 37-kDa subunit of activator 1 (replication factor C) of
      HeLa cells.
AB  - The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase
      epsilon requires the action of two accessory proteins, proliferating cell nuclear
      antigen and activator 1 (A1, also called replication factor C). A1 is an enzyme
      that contains five different subunits (145, 40, 38, 37, and 36.5 kDa). In this
      paper, we describe the isolation of the gene encoding the 37-kDa subunit from
      HeLa cells. This gene was cloned, sequenced, and overexpressed in Escherichia
      coli. The amino acid sequence shows a high degree of homology to the 40-kDa
      subunit of A1; they both contain the identical ATP-binding motif, but in contrast
      to the bacterial expressed 40-kDa protein, the 37-kDa expressed protein did not
      bind ATP. Both the 37- and 40-kDa proteins share substantial homology with the
      phage T4 gene 44 protein and to a lesser extent with the tau and gamma subunits
      of the E. coli DNA polymerase III holoenzyme. Polyclonal antibodies against the
      bacterially expressed 37- and 40-kDa proteins do not crossreact and are specific
      in their interaction. Antibodies against the 37-kDa protein maximally inhibited
      (by 50%) the A1-dependent synthesis of DNA by DNA polymerase delta; antibodies
      against the 40-kDa protein quantitatively inhibited the same reaction. When A1
      dependent synthesis of DNA was partially inhibited by antibodies against the 40
      kDa subunit, the addition of antibodies against the 37-kDa subunit inhibited DNA
      synthesis to a greater extent than the anti-37-kDa antibody alone. These results
      suggest that both the 37- and 40-kDa subunits of A1 are required for the
      biological role of A1 and that they may function differently in this process.

PMID- 1351678
TI  - Spontaneous incorporation of the glycosyl-phosphatidylinositol-linked protein Thy
      1 into cell membranes.
AB  - Thy-1 is a membrane protein that is attached to the plasma membrane by a glycosyl
      phosphatidylinositol anchor. Purified rat brain Thy-1 could be reincorporated
      into the plasma membrane of murine Thy-1- cells directly from aqueous suspension
      and without the use of detergents. A peripheral staining pattern similar to that
      observed for endogenous Thy-1 was achieved. Treatment with phosphatidylinositol
      specific phospholipase C removed nearly all antibody staining due to either
      endogenous or inserted Thy-1. Fluorescence recovery after photobleaching (FRAP)
      was used to compare the lateral mobility of endogenous and inserted Thy-1. Both
      forms exhibited large lateral diffusion coefficients, but with a substantial
      immobile fraction (approximately 50%) indicating that the immobile fraction was
      not due either to chemical differences between inserted and native Thy-1 or to
      some surface Thy-1 molecules having a protein anchor. However, the inserted Thy-1
      failed to activate mouse T lymphocytes upon crosslinking as assayed by
      [3H]thymidine uptake. Since Thy-1 could be directly labeled with rhodamine, the
      effect of the size of the labeling ligand on the mobility obtained by the FRAP
      technique could be explored. Rhodamine-conjugated MRC-OX7 monoclonal antibody or
      its fragments [R-F(ab)2 or R-Fab] were compared with rhodamine as labels for Thy
      1. The measured diffusion coefficients were 1.6 x 10(-9), 2.0 x 10(-9), and 3.2 x
      10(-9) cm2/sec for Thy-1 labeled with R-F(ab)2, R-Fab, and rhodamine,
      respectively; mobile fractions were all in the 40-50% range. Thus, the size of
      the ligand affects the lateral mobility of this labeled membrane protein to a
      measurable extent.

PMID- 1351679
TI  - ERBB2 amplification in breast cancer analyzed by fluorescence in situ
      hybridization.
AB  - We illustrate the use of fluorescence in situ hybridization (FISH) for analysis
      of ERBB2 oncogene copy number, the level of amplification (here defined as the
      ratio of ERBB2 copy number to copy number of chromosome 17 centromeres), and the
      distribution of amplified genes in breast cancer cell lines and uncultured
      primary breast carcinomas. The relative ERBB2 copy number determined by FISH in
      10 breast cancer cell lines correlated strongly with Southern blot results (r =
      0.98) when probes for an identical reference locus were used in the two methods.
      Metaphase analysis of cell lines showed that amplified ERBB2 copies always
      occurred in intrachromosomal clusters but that the number and chromosomal
      location of these clusters varied among the cell lines. In interphase nuclei of
      primary tumors showing ERBB2 amplification (10/44), ERBB2 copies were seen as one
      to four clusters, also suggesting intrachromosomal localization. Regardless of
      the average level of amplification, all these tumors contained highly amplified
      cell subpopulations with at least 25, and sometimes more than 100, ERBB2 copies
      per cell. Tumors that did not show amplification by FISH (34/44) had an average
      of one to five ERBB2 copies scattered randomly in the nuclei and completely
      lacked cells with high copy levels. FISH results on primary tumors were
      concordant with slot blot results on amplification and with immunohistochemical
      detection of overexpression. Quantitative analysis of ERBB2 amplification by FISH
      may improve prognostic assessments based on the pattern of amplification and
      detection of heavily amplified tumor cell subpopulations.

PMID- 1351680
TI  - Genotypic analysis of N-ethyl-N-nitrosourea-induced mutations by Taq I
      restriction fragment length polymorphism/polymerase chain reaction in the c-H
      ras1 gene.
AB  - In genotypic mutation analysis DNA sequence changes are determined without the in
      vivo or in vitro selection of phenotypically altered cells. We have studied the
      induction of base-pair changes by N-ethyl-N-nitrosourea in Taq I endonuclease
      recognition site 2508-2511 (TCGA) of the c-H-ras1 gene in human fibroblasts by
      the restriction fragment length polymorphism/polymerase chain reaction (RFLP/PCR)
      method. This site contains the four bases, and all 12 possible single base-pair
      changes can be monitored. The transition of guanine to adenine at position 2510
      was the major mutation detected by lambda plaque oligonucleotide hybridization
      and quantitative sequence analysis of the RFLP/PCR products. It involves the G
      residue of the CpG sequence of the coding strand. Data calibration with an
      internal mutant standard indicates that absolute frequencies for this transition
      lie in the range of 4-12 x 10(-7). The present study documents the capacity of
      the RFLP/PCR approach to measure mutagen-induced base-pair changes in a specific
      gene sequence without the selection of a phenotypically altered cell.

PMID- 1351681
TI  - Gene conversion in Neisseria gonorrhoeae: evidence for its role in pilus
      antigenic variation.
AB  - Antigenic variation of gonococcal pili results from the unidirectional transfer
      of genetic information from variant-encoding partial pilin genes to an active
      expression locus. Two potential mechanisms that may result in the observed
      alterations of gene linkage and organization are conversion and transformation.
      To determine the relative contributions of these two distinct pathways of
      recombination to pilus variation, gonococcal strains carrying defined frameshift,
      missense, and nonsense mutations within the pilin expression locus were
      constructed. Reversion to a piliated state required correction of the lesions and
      provided a simple means of scoring productive recombination and antigenic
      variation. Examination of the mutants revealed a lack of correspondence between
      the frequencies with which they could be transformed (10(-6) per recipient) and
      the incidence with which they gave rise to revertants (greater than 10(-4) per
      colony-forming unit per generation). Further, the rates of reversion demonstrated
      by these mutants were not altered by growth in the presence of DNase I,
      conditions that abolished intercellular transfer of chromosomal markers during
      cultivation. Through the use of a pilin mutant in which a frameshift mutation
      encompassed the introduction of a restriction endonuclease site, the symmetry of
      recombination that resulted in reversion could be scored by Southern
      hybridization. In all cases examined, the DNA alterations responsible for pilin
      variation were nonreciprocal events. The results favor the model that productive
      pilin gene rearrangements in gonococci arise by gene conversion.

PMID- 1351682
TI  - Fusions near telomeres occur very early in the amplification of CAD genes in
      Syrian hamster cells.
AB  - Previous analyses by fluorescence in situ hybridization of structures present 20
      30 cell generations after the primary events of mammalian gene amplification have
      shown that tens of megabases of DNA separate each copy of the selected gene in
      chromosomal arrays that contain up to 15 copies. Since these structures are very
      unstable, it is necessary to study amplified DNA as soon as possible after it has
      been formed to relate the structures observed to the primary mechanisms that
      generated them. Previously, new amplifications of the CAD gene were analyzed in
      colonies of 10(5) N-(phosphonoacetyl)-L-aspartate-resistant Syrian hamster BHK
      cells. CAD is on the p arm of chromosome B9 and the amplified genes were usually
      found in large extensions of B9p, with one copy in its normal position. We now
      report that dividing drug-resistant cells have been physically separated from
      static drug-sensitive cells, to allow the amplified structures to be observed
      only a few cell generations after they have been formed. The most informative
      results are that about one-third of the newly formed chromosomes carrying
      amplified CAD genes are dicentric and that about half of these carry two B9q
      arms. These observations reveal that recombination between the p telomeric
      regions of two B9 sister chromatids is an important primary event of
      amplification in this system. The resulting dicentric chromosomes can then enter
      bridge-breakage-fusion cycles that provide the means to increase the number of
      CAD genes per cell in successive generations by an asymmetric distribution at
      each cell division.

PMID- 1351683
TI  - Identification of double-stranded RNA-binding domains in the interferon-induced
      double-stranded RNA-activated p68 kinase.
AB  - The double-stranded RNA (dsRNA)-binding domain of the human p68 kinase has been
      localized to the N-terminal half of the enzyme by using progressive deletion
      analysis and in vitro binding assays. To further define the domains responsible
      for binding to dsRNA, we cloned the mouse dsRNA-activated p65 kinase and used
      sequence alignment to identify conserved domains in the N-terminal region.
      Deletions in either of two 12-amino-acid-long and arginine- or lysine-rich
      regions abrogated binding to dsRNA. Moreover, in an in vivo growth inhibition
      assay in the yeast Saccharomyces cerevisiae, these mutants failed to exhibit a
      slow-growth phenotype.

PMID- 1351685
TI  - Rat hepatic microsomal metabolism of oxyprothepine: the role of inhibitors on S
      oxygenation.

PMID- 1351684
TI  - A human serotonin 1D receptor variant (5HT1D beta) encoded by an intronless gene
      on chromosome 6.
AB  - An intronless gene encoding a serotonin receptor (5HT1D beta) has been cloned and
      functionally expressed in mammalian fibroblast cultures. Based on the deduced
      amino acid sequence, the gene encodes a 390-amino acid protein displaying
      considerable homology, within putative transmembrane domains (approximately 75%
      identity) to the canine and human 5HT1D receptors. Membranes prepared from CHO
      cells stably expressing the receptor bound [3H]serotonin with high affinity (Kd 4
      nM) and displayed a pharmacological profile consistent, but not identical, with
      that of the characterized serotonin 5HT1D receptor. Most notably, metergoline and
      serotonergic piperazine derivatives, as a group, display 3- to 8-fold lower
      affinity for the 5HT1D beta receptor than for the 5HT1D receptor, whereas both
      receptors display similar affinities for tryptamine derivatives, including the
      antimigraine drug sumatriptan. Northern blot analysis revealed an mRNA of
      approximately 5.5 kilobases expressed in human and monkey frontal cortex,
      medulla, striatum, hippocampus and amygdala but not in cerebellum, olfactory
      tubercle, and pituitary. The 5HT1D beta gene maps to human chromosome 6. The
      existence of multiple neuronal 5HT1D-like receptors may help account for some of
      the complexities associated with [3H]serotonin binding patterns in native
      membranes.

PMID- 1351686
TI  - The effect of SRIF on the EEG sleep of normal men.
AB  - The aim of this investigation was to evaluate EEG sleep, especially measures of
      delta-wave sleep, during and after the administration of somatostatin (SRIF).
      Eleven normal men, ages 22-37 yr, were administered saline or SRIF (0.1
      microgram/kg/min IV) over 160 min at bedtime. SRIF delayed sleep-related growth
      hormone (GH) secretion without altering the amount of GH available during the
      entire night of sleep. No changes in delta-wave sleep occurred during either the
      first 100 min of sleep or the remainder of the night. Furthermore, all major EEG
      sleep variables were not significantly different between the saline and SRIF
      infusion night. It would not appear that the peripheral administration of this
      dose of SRIF or the subsequent delay of GH release has quantitative effects on
      EEG measures of all-night sleep.

PMID- 1351687
TI  - Non-neuroleptic treatment of behavioral symptoms and agitation in Alzheimer's
      disease and other dementia.
AB  - Both neuroleptic and nonneuroleptic medications are widely used to treat
      symptomatic behaviors in dementia patients. There is a substantial body of
      literature suggesting that neuroleptics are modestly effective in treating these
      symptoms, but the magnitude of their effect is limited. Nonneuroleptic
      medications, such as anticonvulsants and antidepressants, have been advocated as
      useful in treating certain symptoms but have not been as well studied. This
      article critically reviews the published evidence for the effectiveness of
      selected nonneuroleptic medications in treating behavioral symptoms in elderly
      dementia patients, especially those with possible Alzheimer's disease (AD). The
      literature consists almost entirely of clinical series and case reports, making
      interpretations of the efficacy of individual medications difficult. With the
      singular exception of the serotonin uptake blocker citalopram, the few placebo
      controlled studies are of small sample sizes, showing at best very modest
      efficacy for the study medication. Despite their widespread use, there is very
      little published, empirical evidence for the effectiveness of these agents for
      treating behavioral symptoms in elderly dementia patients.

PMID- 1351688
TI  - Disclosure of tardive dyskinesia: effect of written policy on risk disclosure.
AB  - Over half of the states in the country have written statutory and/or regulatory
      policies that require psychiatrists treating inpatients within the state mental
      health system to disclose risks associated with treatment to voluntarily admitted
      patients. A severe side effect associated with the long-term use of neuroleptic
      medication is tardive dyskinesia (TD). A nationwide study was conducted to
      investigate the effect of written risk disclosure policy on psychiatrists' self
      reported disclosure of the risks associated with neuroleptics to individuals
      diagnosed as having schizophrenia of a chronic nature. Participating in the study
      were 520 psychiatrists from 94 state/county mental hospitals located in 35
      states. Fifty-four percent of those psychiatrists reported that they typically
      disclosed TD to the target patient population. The study results did not support
      the hypothesis that the presence of statutory and regulatory policy on disclosure
      of risk results in psychiatrists typically disclosing TD to patients.

PMID- 1351689
TI  - Alternative approaches to the discovery of novel antipsychotic agents.

PMID- 1351690
TI  - [Acute febrile backache revealing hemorrhagic fever with renal syndrome].

PMID- 1351691
TI  - Urinary incontinence in children -- focusing on daytime wetting. Proceedings of a
      workshop. Beaune, France, 11 April 1991.

PMID- 1351692
TI  - Prognostic factors in breast cancer.

PMID- 1351693
TI  - Concurrent adrenal pheochromocytoma and papillary adenocarcinoma of the thyroid
      in a 20-year-old man.
AB  - A 20-year-old man was admitted to Kyushu University Hospital with complaints of
      severe headache and episodic hypertension (200/100 mmHg). Ultrasonograms and
      computed tomographs revealed tumors in the left adrenal region and in the right
      lower lobe of the thyroid gland. Total thyroidectomy and left adrenalectomy were
      performed. The excised thyroid tumor and adrenal tumor were pathologically
      diagnosed as papillary adenocarcinoma and pheochromocytoma, respectively. A
      chromosome analysis revealed no karyotypic abnormality. Whereas the world
      literature records such occurrences in women, this is the first report of a
      simultaneous occurrence of pheochromocytoma and papillary adenocarcinoma of the
      thyroid in a young man.

PMID- 1351695
TI  - [The relation between cognitive deficits and schizophrenic symptoms].
AB  - Reasons are given for explicitly derived requirement that experimental
      psychological investigations of cognitive deficits of schizophrenics should be
      related to their clinical symptoms. Results which verify this relations prove to
      be relevant for prognosis, therapy and rehabilitation of schizophrenic patients.

PMID- 1351694
TI  - Natural scrapie in British sheep: breeds, ages and PrP gene polymorphisms.
AB  - One hundred and sixty-seven sheep of 32 breeds and crossbreeds affected by
      natural scrapie throughout Britain were tested for the presence of restriction
      fragment length polymorphisms of the PrP gene observed when their DNA was
      digested with EcoRI or HindIII. These polymorphisms have already been associated
      with different susceptibilities to experimental scrapie (controlled by alleles of
      the Sip gene) in a flock of Cheviot sheep. In two studies 86 to 92 per cent of
      the sheep were found to carry the PrP gene EcoRI fragment e1 which is associated
      with high susceptibility (or the sA allele of Sip) to experimental scrapie. The
      PrP gene HindIII genotypes of the natural scrapie sheep were not apparently
      associated with differences in susceptibility to scrapie. There was no link
      between the polymorphisms and the age or breed of the affected sheep.

PMID- 1351696
TI  - [Use of pronouns: formal and functional aspects in the early phases of language
      development].
AB  - This article presents findings from empirical studies of the development of the
      use of pronouns in early child language. This presentation includes discussion of
      1) when personal, reflexive, possessive, and indefinite pronominal forms appear
      in child-initiated contexts, 2) which errors emerge, and 3) which communicative
      functions utterances with pronouns have in dialogue. A first comparison of German
      speaking and (American-)English-speaking children's usage is offered, focussing
      in particular on the use of the pronominal forms I/ich, you/du, and my/mein. This
      crosslinguistic comparison reveals differences in the age of first use, but
      simultaneously suggests similarities in functional characteristics of such usage.
      The findings are discussed in connection with the question of the development of
      children's communicative competence.

PMID- 1351697
TI  - Is guanylate cyclase activation through the release of nitric oxide or a related
      compound involved in bradykinin-induced perivascular primary afferent excitation?
AB  - In dogs under light thiopentobarbital anesthesia, intracarotid injection of
      bradykinin (BK) causes a dose-dependent "pain response" represented by hyperpnea,
      bradycardia, vocalization and ipsilateral contraction of the sternocephalic
      muscle. These events result from the activation of primary afferent nerves
      located in the wall of the carotid vessels distributed mainly in occipital artery
      territory. We present evidence indicating that these BK-induced reflex phenomena
      are 1) mediated by the activation of B2 receptors; 2) potentiated by
      prostaglandin E2 (PGE2) and serotonin (5-HT) the latter acting via sub-type 5-HT3
      receptors; 3) reduced by indomethacin and/or NG-nitroarginine, and 4) abolished
      by methylene blue. These results suggest that 5-HT plays a modulatory role on BK
      action; the latter depends on the release of prostaglandins and nitric oxide or a
      related compound and includes the activation of guanylate cyclase which appears
      to be involved in primary afferent excitation.

PMID- 1351698
TI  - Synthesizing embryology and human genetics: paradigms regained.

PMID- 1351699
TI  - gamma-Glutamyltransferase isoenzyme pattern in workers exposed to
      tetrachloroethylene.
AB  - In compliance with the mandatory medical surveillance of workers exposed to
      tetrachloroethylene (PCE) in Italy, isoenzyme fractioning of serum gamma
      glutamyltransferase (GGT) was performed on 141 workers of both sexes and on 130
      control subjects. None of the workers showed any clinical symptoms of liver
      disease and their enzymatic profiles, including AST, ALT, 5'-NU, ALP, and GGT,
      were within the normal reference limits. A statistically significant increase in
      total GGT serum level was found in the exposed subjects, which was associated
      with an increase in one of the two fractions normally present in healthy
      individuals (GGT-2), as well as with the appearance and progressive increase of
      the level of a fraction (GGT-4) considered to be an expression of hepato-biliary
      impairment. Further research is ongoing among these workers, which will clarify
      whether or not electrophoretic GGT tests may be useful in detecting liver
      function changes due to occupational exposure to PCE.

PMID- 1351701
TI  - 3rd International Conference on the Neuronal Ceroid Lipofuscinoses (Batten
      disease). Indianapolis, Indiana, May 30-June 1, 1990.

PMID- 1351700
TI  - Molecular study of 45,X conceptuses: correlation with clinical findings.
AB  - The parental origin of the single X in 45 cases (40 liveborns and 5 fetuses) with
      a 45,X karyotype was studied using polymorphic DNA probes. The single X was
      paternal in origin (Xp) in 10 cases (22.2%) and maternal (Xm) in 35 cases
      (77.8%). Y chromosome material was detected in 1 out of the 35 cases with a 45,Xm
      constitution. Analysis of parental ages and clinical data of the patients with
      respect to the origin of the single X revealed no significant differences between
      the origins.

PMID- 1351702
TI  - Mapping the gene for juvenile onset neuronal ceroid lipofuscinosis to chromosome
      16 by linkage analysis.
AB  - The ceroid-lipofuscinoses are a group of inherited neurodegenerative disorders
      characterised by the accumulation of autofluorescent lipopigment in neurones and
      other cell types. The underlying biochemical defect is unknown. Juvenile onset
      neuronal ceroid lipofuscinosis (Batten disease; Spielmeyer-Vogt disease) is an
      autosomal recessive trait. Linkage studies were undertaken to determine the
      location of the Batten disease (CLN3) mutation. Studies were carried out on 205
      members of 42 families in which there were 76 affected individuals. Families
      originated from 7 North European countries and Canada. Serum samples from 23
      families, including a total of 48 affected children, were tested for a set of
      "classical markers." A positive lod score was found with the haptoglobin (Hp)
      system. The combined male and female maximum lod score was 3.00 at theta = 0.00
      and theta = 0.26, respectively. This provided an indication of localisation to
      the long arm of chromosome 16. Linkage analysis was then carried out in 42
      families using DNA markers for loci on human chromosome 16. The maximal lod score
      between Batten disease and the locus D16S148 calculated for combined sexes was
      6.05. No recombinants were observed. Multilocus analysis using 5 loci indicated
      the most likely order to be HP-D16S151-D16S150-CLN3-D16S148-D16S147. Work is in
      progress to refine the genetic and physical localisation of the Batten disease
      gene using additional markers in this region and a panel of somatic cell hybrids.
      Methods are now available which should allow the gene to be isolated and
      characterised.

PMID- 1351704
TI  - Combined scientific meeting of the Australian Society of Anaesthetists and
      Canadian Anaesthetists's Society, Brisbane, Queensland, October 1991. Abstracts.

PMID- 1351703
TI  - Brief treatment of emergency room patients with panic attacks.
AB  - OBJECTIVE: Most research on treatment for panic disorder has involved chronic
      forms of the illness. To determine the efficacy of early intervention, the
      authors examined the effects of treatment for patients with panic attacks who
      were seen in the emergency room, which is the first point of contact with the
      health delivery system for many persons with panic attacks. METHOD: The subjects
      were 33 patients with panic attacks seen in two emergency rooms. The presence of
      panic attacks was confirmed with a modified version of the Structured Clinical
      Interview for DSM-III-R; approximately 40% of the patients met the DSM-III-R
      criteria for panic disorder with agoraphobia. The patients were randomly assigned
      to groups receiving reassurance (N = 16) or exposure instruction (N = 17). Scores
      on the Fear Questionnaire agoraphobia subscale, Mobility Inventory, and Beck
      Depression Inventory and the frequency of panic attacks were determined at
      baseline, 3 months, and 6 months. RESULTS: The subjects who received exposure
      instruction significantly improved over the 6-month period on depression,
      avoidance, and panic frequency. The reassurance subjects did not improve on any
      measure and eventually reported more agoraphobic avoidance. CONCLUSIONS: These
      results suggest that early intervention with exposure instruction may reduce the
      long-term consequences of panic attacks. The exposure instruction was of value
      even though the subjects had relatively low levels of avoidance at the outset of
      the study.

PMID- 1351706
TI  - On the uptake of Wuchereria bancrofti microfilariae in vector mosquitoes of
      different susceptibility to filarial infections.
AB  - The quantitative uptake of Wuchereria bancrofti microfilariae by mosquito species
      of different susceptibility to filarial infection was studied. There was no
      relationship between the degree of susceptibility and the number of ingested
      microfilariae. However, in all tested mosquito strains the females ingested as a
      mean 1.2-1.9 times more microfilariae of W. bancrofti than expected.

PMID- 1351705
TI  - The influence of atropine dose on recovery from vecuronium-induced neuromuscular
      blockade.
AB  - To determine whether the dose of atropine affects the rate of neostigmine-induced
      recovery from vecuronium-induced neuromuscular blockade, the authors monitored
      isometric adductor pollicis mechanical activity in 36 anesthetized (thiopental,
      fentanyl, nitrous oxide) adult patients (ASA physical status 1 or 2). Once
      surgery was completed and twitch height had spontaneously regained 25% of its
      initial value, the patients were randomly allocated into three groups (A10, A15,
      A20; n = 12 in each group) according to the dose of atropine (10, 15, or 20
      micrograms/kg) that was mixed with 40 micrograms/kg neostigmine. Twitch height,
      train-of-four, and 50- and 100-Hz tetanic fade were recorded for 15 min after the
      administration of the reversal agents. No significant differences were found
      among the three groups in the final twitch height (95% +/- 2%), train-of-four
      (87% +/- 1%, 88% +/- 2%, 89% +/- 1%), and 50-Hz tetanic fade (90% +/- 1%, 94% +/-
      1%, 93% +/- 1%) (mean +/- SEM). Fifteen minutes after reversal, fade in response
      to 100-Hz tetanus was statistically greater in the A10 group than in the two
      other groups (70% +/- 3% of control versus 84% +/- 4% and 81% +/- 2%) (mean +/-
      SEM, P less than 0.05). The present results demonstrate that larger doses of
      atropine facilitate neostigmine's reversal of vecuronium neuromuscular blockade.
      The clinical implications of the differences observed in this study remain to be
      determined.

PMID- 1351707
TI  - Clinical presentation and treatment of black widow spider envenomation: a review
      of 163 cases.
AB  - STUDY OBJECTIVE: To review cases of black widow spider envenomation to describe
      the clinical presentation and evaluate the efficacy of treatment. DESIGN:
      Retrospective chart review. SETTING: An urban toxicology referral center. TYPE OF
      PARTICIPANTS: All patients attended by the toxicology service and discharged from
      our hospital between January 1982 and December 1990 with a diagnosis of black
      widow spider envenomation. INTERVENTIONS: Inclusion criteria were either a
      positive black widow spider identification or a visible envenomation site
      ("target lesion"). Depending on the clinical presentation, patients were
      categorized as grade 1, 2, or 3 in severity. The efficacy and side effects of
      treatment alternative were evaluated. MEASUREMENTS AND MAIN RESULTS: One hundred
      sixty-three patients met the inclusion criteria. The most common sites of
      envenomation were the upper and lower extremities. The most common presenting
      complaint was generalized abdominal, back, and leg pain. One hundred eighteen
      patients initially presented to our institution, and 45 were transfers. Pain
      relief of grade 2 and 3 envenomations was achieved most effectively with either
      black widow spider-specific antivenin alone or a combination of IV opioids and
      muscle relaxants. Fifty-eight patients received antivenin with complete
      resolution of symptoms in a mean time of 31 +/- 26.7 minutes. Of the 118 patients
      initially seen at our institution, the mean total duration of symptoms was 9 +/-
      22.7 hours in patients receiving antivenin and 22 +/- 24.9 hours in patients not
      receiving antivenin. Fifty-two percent of patients not receiving antivenin
      required hospitalization, whereas only 12% of those receiving antivenin were
      admitted. One patient died of severe bronchospasm after receiving antivenin.
      Calcium gluconate was not effective in providing symptomatic relief in this
      series, with 96% of the grade 2 and 3 envenomations treated initially with
      calcium gluconate requiring the addition of IV opioids or other analgesics for
      symptomatic relief. Fifty-five percent of patients initially receiving IV
      morphine and 70% of those initially receiving both IV morphine and
      benzodiazepines obtained symptomatic relief without additional medication.
      CONCLUSION: One hundred sixty-three envenomations by black widow spiders were
      reviewed and graded according to severity with treatment modalities evaluated.
      Although calcium gluconate usually has been considered the first-line treatment
      of severe envenomations by black widow spiders, we found it ineffective for pain
      relief compared with a combination of IV opioids and benzodiazepines. The use of
      antivenin significantly shortened the duration of symptoms in severe
      envenomations.

PMID- 1351708
TI  - [Takayasu's disease disclosed by isolated involvement of the ascending aorta].
AB  - The authors report the histological discovery of a case of Takayasu syndrome
      affecting the ascending aorta. This involvement appearing to concern only the
      aorta, with no symptomatic complaints nor any laboratory abnormalities indicative
      of an inflammatory syndrome, corticosteroids were not prescribed. Management
      consisted of biennial monitoring by transthoracic and transesophageal
      ultrasonography of the aorta and the supra-aortic main vessels together with
      monitoring of laboratory parameters.

PMID- 1351709
TI  - Accessibility and function of human thyroid epithelial cells in monolayer
      culture.
AB  - Measurement of thyroid stimulating immunoglobulins (TSI) has not yet found
      widespread application in the diagnosis and management of Graves' disease. One of
      the problems is the poor and variable sensitivity of the different assays. We
      therefore studied the influence of the accessibility of the basal part of human
      thyroid epithelial cells in monolayer culture on their cAMP response to thyroid
      stimulating hormone (TSH) and TSI. Test media containing either ammoniumsulphate
      precipitated globulin fractions of sera from normal controls and treated or
      untreated patients with Graves' disease or TSH were used to stimulate cAMP
      production by cryopreserved human thyroid epithelial cells in monolayer culture.
      Incubations with and without the use of porous membrane inserts as culture
      surface were compared by univariate parametric and non-parametric testing. It
      appears that more TSH-receptors, probably on the basal part of the thyrocyte, can
      be exposed to the medium by using a porous membrane as culture surface as
      demonstrated by the increased analytical sensitivity of the semi-bioassay of TSH
      and TSI.

PMID- 1351710
TI  - Mucin 4 (MUC4) gene: regional assignment (3q29) and RFLP analysis.
AB  - The use of a probe (JER64) containing a mucin 4 (MUC4) cDNA insert of 1.83 kb
      allowed to assign by in situ hybridization, the MUC4 gene to 3q29. This probe
      detected RFLPs with all restriction enzymes used (BamHI, HindIII, PstI, EcoRI,
      and TaqI). Particularly numerous alleles were observed with PstI, EcoRI and TaqI,
      in a small sample of unrelated DNAs (25 digested with PstI, 8 with EcoRI and 8
      with TaqI). The PIC values were 0.69, 0.63 and 0.70 for PstI, EcoRI and TaqI
      respectively. The polymorphisms observed of variable number of tandem repeat
      (VNTR) type are in relation with the presence of tandemly repeated nucleotide
      sequences in MUC4 gene.

PMID- 1351711
TI  - Adjunctive therapy of experimental meningitis: agents other than steroids.

PMID- 1351712
TI  - Genetic characterization of Legionella pneumophila serogroup 1 associated with
      respiratory disease in Australia.
AB  - Techniques were developed for genetic characterization of Legionella pneumophila
      serogroup 1 by using restriction fragment length polymorphism analysis. Allozyme
      analysis provided an index of the discrimination achieved by restriction fragment
      length polymorphism. Isolates from human cases of legionellosis were examined by
      both methods, and their profiles were compared with reference strains of L.
      pneumophila serogroup 1 obtained from the American Type Culture Collection.
      Eighteen distinct clones were evident among the isolates examined. Both methods
      could be used to trace the source of an outbreak of legionellosis caused by L.
      pneumophila serogroup 1.

PMID- 1351714
TI  - Reactive hyperemia in the nonused internal mammary artery after median
      sternotomy.
AB  - Doppler spectrum analysis was performed in the nonused internal mammary artery in
      a group of patients who underwent myocardial revascularization using the
      contralateral internal mammary artery and in both internal mammary arteries in a
      group of patients who underwent median sternotomy for cardiac surgical procedures
      in which the internal mammary artery was not used. In all nonused internal
      mammary arteries the preoperatively triphasic systolic flow pattern had
      postoperatively converted into a unidirectional systolic flow pattern with a
      large diastolic flow component, characterized by a significant increase in the
      diastolic flow parameters and a significant decrease in the resistance and
      pulsatility indices. This effect had almost subsided at 6 months postoperatively.
      This study indicates that the reactive hyperemia observed in the nonused internal
      mammary artery in the early postoperative period is mainly caused by the
      temporarily increased metabolic demand of the anterior thoracic wall and
      mediastinum, rather than by the metabolic demand of the anterior diaphragm and
      the contralateral rectus abdominis muscle after deprivation of their main
      nutritional vessel.

PMID- 1351713
TI  - Immunohistochemical localization of proliferating cell nuclear antigen/cyclin in
      human skin.
AB  - Expression of proliferating cell nuclear antigen/cyclin (PCNA/cyclin) in skin
      tissue specimens and cultured keratinocytes was studied using a monospecific
      antibody, obtained from a patient with systemic lupus erythematosus, and a
      monoclonal antibody. Indirect immunofluorescent staining revealed that cultured
      keratinocytes obtained from human foreskins expressed PCNA/cyclin as variable
      nuclear patterns in 15-30% of the cells. In normal human skin tissue specimens,
      PCNA/cyclin was demonstrated in only a few basal cells. Interestingly,
      PCNA/cyclin was expressed strongly in almost all the cells of the lowest layer of
      the epidermis adjacent to squamous cell carcinomas, whereas the tumor aggregates
      themselves had no positive staining. In contrast, no such characteristic staining
      was demonstrated in specimens of basal cell carcinoma. The staining pattern of
      PCNA/cyclin was different from that of Ki-67 in the skin tissue specimens. Our
      results suggest that PCNA/cyclin could be a useful marker of cell proliferation.

PMID- 1351715
TI  - Competitive flow from a fully patent coronary artery does not limit acute mammary
      graft flow.
AB  - The shriveled, stenotic mammary graft sometimes observed after internal mammary
      artery (IMA) to coronary artery bypass grafting has been attributed to
      competitive flow from the insufficiently stenosed native coronary vessel. To
      study further the effects of native coronary artery competing flow on IMA graft
      flow, 10 dogs (mean weight, 23.5 +/- 3.69 kg) underwent coronary artery bypass
      grafting using the pedicled left IMA anastomosed to a normal, fully patent
      proximal circumflex (CFX) coronary artery. The procedure was performed through a
      left thoracotomy, off pump, using a brief local occlusion to perform the
      anastomosis. Native in situ IMA flow, CFX flow distal to the anastomosis, and IMA
      graft flow were measured using calibrated electromagnetic flow probes. When the
      CFX proximal to the anastomosis was occluded transiently, IMA flow increased to
      supply 100% of the previously measured distal CFX flow (60.2 +/- 7.9 mL/min).
      When both the IMA graft and CFX proximal to the anastomosis were patent, total
      distal perfusion was maintained (58.9 +/- 7.8 mL/min) and relative IMA graft flow
      (26.5 +/- 3.3 mL/min) was proportional to the relative diameter of the IMA graft
      to the native coronary artery (r = 0.96). The mean flow in the IMA in situ on the
      chest wall before its division was 23.8 +/- 8.1 mL/min. These results suggest
      that, at least acutely in a canine model, IMA graft flow is maintained above in
      situ levels even when grafted to a completely patent coronary artery and that
      acute competitive flow probably does not cause mammary artery shriveling.

PMID- 1351716
TI  - [Cow's milk protein intolerance and hypoallergenic milk].

PMID- 1351717
TI  - Early bile duct carcinoma.
AB  - The clinocopathologic features of seven patients with early bile duct carcinoma
      are reported. Early bile duct carcinoma has been defined as bile duct carcinoma
      limited to the bile duct wall. The seven patients included six men and one woman
      ranging in age from 44 to 77 years. Six patients complained of jaundice and the
      other presented with right hypochondralgia. Ultrasonography showed a dilated
      proximal bile duct in the seven with a polypoid mass in three. Computerized
      tomography showed a dilated biliary tree in the seven together with a polypoid
      mass in two. Direct visualization of the bile duct with endoscopic retrograde
      cholangiography and/or percutaneous transhepatic cholangiography showed a
      polypoid tumour of the bile duct and a dilated proximal biliary tree in all
      seven. Each of the seven polypoid tumours were well differentiated papillary or
      tubular adenocarcinoma restricted to the bile duct wall with minimal stromal
      invasion. There was neither any lymph node metastasis nor perineural invasion.
      Five of the seven patients were doing well at 24-112 months after a complete
      resection. One patient died from multiple liver metastases 21 months after
      intervention. The other patient died from other diseases 138 months after
      operation. These seven cases can be classified as early bile duct carcinoma due
      to both the limited invasion and favourable prognosis. The clinical features of
      the seven patients were quite similar to those of usual bile duct carcinoma.
      However there are still no proper diagnostic clues for early bile duct carcinoma
      and these patients represent fortunate cases that clinicians happened to discover
      by chance.

PMID- 1351719
TI  - Long survivors after pancreatoduodenectomy for pancreas head carcinoma.
AB  - Twelve Japanese patients with pancreas head carcinoma who survived 3 years or
      more after a pancreatoduodenectomy and 50 who survived less than 12 months were
      reviewed clinicopathologically. The 12 patients who survived for greater than or
      equal to 3 years exhibited more favourable prognostic factors: a higher incidence
      of jaundice; a smaller mass; a higher prevalence of an earlier stage tumour and
      adenocarcinoma of differentiated type; and a lower incidence of venous invasion,
      lymph node metastasis, and cancer cells at the surgical margins. However the
      difference was not significant. Univariate log-rank analysis regarding 13
      prognostic variables showed that histologic type was a significant factor but
      multivariate Cox regression analysis failed to reveal an independent significant
      parameter. Nine of the 12 long-term survivors showed lymph node metastasis and
      six of the 12 revealed cancer cells at the surgical margins. Six of the 12 long
      term survivors died from local recurrence and/or distant metastasis 37-78 months
      after operation. Only two patients survived more than 5 years after the
      operation. At the time of writing, one of them was still alive and another was
      dead 78 months after the operation. Pancreatoduodenectomy for pancreas head
      carcinoma infrequently offers a permanent cure for the patients with pancreas
      head carcinoma but sometimes produces a worthwhile long-term survival, even if
      the resected margins were affected by malignant cells or the lymph node
      metastasis was evident.

PMID- 1351718
TI  - Iatrogenic injuries to the extrahepatic biliary tract.
AB  - Iatrogenic injuries to the extrahepatic biliary tract continue to occur and
      result in significant morbidity. Over the last 10 years, 26 patients have been
      referred to Westmead Hospital for management of iatrogenic biliary tract
      injuries. Of these injuries, 22 occurred during cholecystectomy, three during
      hepatectomy and one during a pancreaticoduodenectomy. The principles of avoidance
      and repair are discussed. It is concluded that these injuries, although uncommon,
      continue to occur and that the best treatment results are achieved in specialized
      hepatobiliary units.

PMID- 1351720
TI  - Unexpected growth-stimulatory effect of somatostatin analogue on cultured human
      pancreatic carcinoid cells.
AB  - Therapeutic efficacy of a synthetic somatostatin analogue for the treatment of
      carcinoid tumors is still controversial. In vivo studies performed in our
      laboratory showed that a somatostatin analogue, SMS 201-995, significantly
      inhibited growth of human pancreatic carcinoid (BON) tumors xenotransplanted into
      athymic nude mice. In the present study, however, SMS 201-995 did not inhibit in
      vitro growth of BON cells, but rather SMS 201-995 stimulated growth in a dose
      dependent fashion. The growth-stimulatory effect was likely mediated through the
      reduction of cyclic AMP production. Unsuccessful treatment of certain types of
      carcinoid tumor with SMS 201-995 may be partly due to the direct growth
      stimulatory effect of SMS 201-995 on carcinoid cells.

PMID- 1351721
TI  - Identification of a processed protein related to the human chaperonins (hsp 60)
      protein in mammalian kidney.
AB  - The chaperonin family of proteins, which includes GroEL protein of E. coli, yeast
      heat shock protein (hsp-60) and the ribulose-1-5-bisphosphate carboxylase (Rubis
      Co.) subunit binding protein of plant chloroplasts, shows strong sequence
      homology to the Chinese hamster ovary (CHO) mitochondrial P1 protein. We have
      identified a 60 kDa protein from bovine kidney which by N-terminal sequencing
      gives the amino acid sequence AKDVKFGADARALLMLQGVDLLADA. Bovine whole kidney
      membranes were delipidated, solubilized with octyl glucoside and fractionated
      over an affinity column using the amiloride analog 5-N pyrazine amiloride as the
      ligand. After extensive washing with 200 mM NaCl, the column was eluted with pH
      4.0 buffer. Analysis of column fractions on a 7.5% polyacrylamide gel revealed 3
      4 bands with a predominant band at 60,000 Da. Amino acid analysis after transfer
      to immobilon membranes demonstrated sequence identity to the human HSP (60),
      extending 24 amino acids from the N-terminus, but lacking the leader sequence.
      These data indicate that a processed form of a protein related to the human HSP
      (60) chaperonin is associated with a membrane fraction in the mammalian kidney,
      and that the processed form of the protein binds strongly to an amiloride
      affinity support.

PMID- 1351722
TI  - Selective cell-surface expression of dipeptidyl peptidase IV with mutations at
      the active site sequence.
AB  - The cell surface expression of dipeptidyl peptidase IV (DPPIV) was examined in
      COS-1 cells transfected with its cDNA with or without mutations at the active
      site sequence Gly-Trp-Ser-Tyr-Gly (positions 629-633). Mutants with substitution
      of Trp630----Glu or Ser631----Ala were expressed on the cell surface as normally
      as the wild-type DPPIV, although the mutant with Ala631 had no enzyme activity.
      In contrast, any single substitutions of Gly at positions 629 and 633 resulted in
      no surface expression of the mutants, which were, instead, detected within the
      cells. When Tyr632 was substituted, one mutant (Tyr----Phe) was expressed on the
      surface, whereas the others (Tyr----Gly or Leu) were intracellularly retained.
      These results indicate that the surface expression of DPPIV is critically
      influenced by mutations at the active site sequence.

PMID- 1351723
TI  - Identification of homeobox-containing genes expressed in hematopoietic blast
      cells.
AB  - Among putative candidates involved in commitment and differentiation of
      hematopoietic cells are homeoproteins, a large family of transcription factors
      playing a major role during development. Using a polymerase chain reaction (PCR)
      derived protocol, we have investigated for Antennapedia-like homeobox-containing
      (HOX) gene expression in an enriched population of human hematopoietic
      progenitors. Nine members of HOX 1 and HOX 2 loci were isolated. Together with
      recent studies using established cell lines, this indicates a large
      representation of HOX genes in the hematopoietic compartment and suggests a
      participation of this class of nuclear proteins to early steps of hematopoiesis.

PMID- 1351724
TI  - Ebrotidine--a new H2-receptor antagonist with mucosal strengthening activity.
AB  - The mechanism of gastric mucosal protection by ebrotidine against ethanol-induced
      mucosal injury was investigated in rats treated intragastrically either with the
      drug or vehicle. Results of macroscopic assessment revealed that ebrotidine at
      doses of 50mg and higher/kg body weight effectively prevented mucosal injury, and
      that the maximal protective effect was achieved by 1h. Physicochemical analysis
      established that ebrotidine evoked 30% increase in mucus gel dimension, and
      showed 20% increase in phospholipids, and the content of sulfo- (18%) and
      sialomucins (21%). This was accompanied by 1.4-fold increase in mucus gel
      viscosity, 16% increase in H+ retardation capacity, and 65% increase in
      hydrophobicity. Our data show that ebrotidine is a unique H2-antagonist capable
      of enhancement of the physicochemical characteristics of gastric mucus.

PMID- 1351725
TI  - Effect of nitroso complexes of some transition metals on the activity of soluble
      guanylate cyclase.
AB  - Effects of nitroso complexes of some transition metals (Fe, Co, Cr), differing in
      the character of NO oxidation on the activity of human and rat platelet guanylate
      cyclase were studied. 3 types of nitroso complexes were used: (1) NO group
      carries a positive charge--a nitrosonium cation (Na2[FeNO + (CN)5]
      nitroprusside); (2) NO is neutral--(K3[CrNO(CN)5 and [CoNO(NH3)5]SO4) and (3) NO
      is coordinated as anion NO- (K3[CoNO-(CN)5]. It is shown that the highest
      stimulatory effect is produced by sodium nitroprusside, whose activating action
      is due to the interaction of its NO group with the guanylate cyclase heme.
      Nitroso complexes (Co and Cr) the NO group of which is neutral stimulated
      guanylate cyclase activity insignificantly and this activation was not guanylate
      cyclase heme directed. Nitroso complex (Co) with NO coordinated as anion NO(-)-
      is a guanylate cyclase inhibitor. In contrast to nitroprusside, the nitroso
      complexes used (Co and Cr) have no hypotensive effect. It was concluded that the
      essential requirement for the realization of the hypotensive effect of transition
      metals' nitroso complexes is the ability of these compounds to activate soluble
      guanylate cyclase solely by the heme-dependent mechanism.

PMID- 1351726
TI  - The effects of sulphasalazine and its metabolites on prostaglandin production by
      human mononuclear cells.
AB  - Although it has been proposed that sulphasalazine (SASP) and its metabolite 5
      aminosalicylic acid (5-ASA) act therapeutically by inhibiting production of
      vasoactive and immunoregulatory prostaglandins (PGs), in previous in vitro
      studies these drugs have both inhibited and promoted PG production. This study
      demonstrates that SASP and 5-ASA promote or inhibit peripheral blood mononuclear
      cell PG production depending upon the PG measured, the concentration of the drug,
      and whether the cells were stimulated. Sulphapyridine, the other constituent of
      SASP, only inhibited production. At high concentrations of SASP and 5-ASA the
      viability of mononuclear cells was reduced. The enhancement of PG production and
      toxicity was greater with SASP than 5-ASA, while the PGs most affected by SASP
      were not those most affected by 5-ASA. Thus, in vitro SASP may possess properties
      other than those of 5-ASA and this may explain the different therapeutic
      properties of these two compounds.

PMID- 1351728
TI  - Beta-adrenoceptor blocking effects of two bopindolol metabolites in isolated
      guinea-pig atria.
AB  - The beta-adrenoceptor blocking effects of the bopindolol (Wandonorm, CAS 62658-63
      3) metabolites 18-502 (indole-2,4- methylaminopropoxy(N-tert.butyl)-tartrate) and
      20-785 (indole-2,4-carboxyaminopropoxy(N-tert.butyl] were studied in electrically
      stimulated guinea-pig left atria and in spontaneously beating guinea-pig atria in
      vitro. Both compounds shifted the concentration-response curve of isoprenaline to
      the right, but did not reduce the maximum effect of this drug. For compound 20
      785, pA2 values of 7.44 (left atrium, inotropic effect) and 7.58 (right atrium,
      chronotropic effect) were calculated. The metabolite 18-502 had a much greater
      beta-adrenoceptor blocking potency, as judged from its pA2 values of 9.53 and
      9.48, resp., and in the concentration of 10(-8) mol/l it caused a significant
      flattening of the concentration-response curve of isoprenaline. From these
      results, compound 20-785 can be classified as a competitive beta-adrenoceptor
      antagonist, while for higher concentrations of the metabolite 18-502 additional
      noncompetitive mechanisms of action cannot be excluded.

PMID- 1351727
TI  - Sulfated alkyl oligosaccharides with potent inhibitory effects on human
      immunodeficiency virus infection.
AB  - Compounds with medium relative molecular masses active against human
      immunodeficiency virus (HIV) were synthesized. Sulfated alkyl oligosaccharides
      such as sulfated octadecyl maltohexaoside, sulfated dodecyl laminaripentaoside
      and sulfated dodecyl laminari-oligomer caused 50% inhibition of virus infection
      in the EC50 range of 0.4-0.7 microgram/mL in vitro using the MT-4 cell line and
      HIV-1HTLV-IIIB virus isolate, though sulfated oligosaccharides without alkyl
      groups showed low anti-HIV activities. This anti-HIV activity was close to the
      EC50 of 0.43 microgram/mL for a highly active sulfated polysaccharide curdlan
      sulfate which was reported to inhibit completely the HIV infection at a
      concentration as low as 3.3 micrograms/mL. These compounds were also active
      against HIV-2 and a clinically isolated HIV-1 with reduced AZT sensitivity. For
      such sulfated alkyl oligosaccharides, the mechanism of inhibition of HIV
      infection was assumed to be the inhibition of HIV binding to the cell and to some
      extent the interaction of the alkyl portion with the lipid bilayer of the virus.

PMID- 1351729
TI  - Characterization of plastid 5-aminolevulinate dehydratase (ALAD; EC 4.2.1.24)
      from spinach (Spinacia oleracea L.) by sequencing and comparison with non-plant
      ALAD enzymes.
AB  - We have sequenced 5-aminolevulinate dehydratase (ALAD; EC 2.4.1.24) of a plant. A
      full-length cDNA clone (1727 bp) encoding this enzyme has been identified by
      immunoscreening a lambda gt 11 cDNA library of spinach. ALAD is not a plant
      specific enzyme; however, the plant enzyme differs from the well known ALAD
      enzymes of bacteria, yeast and animals in structural and biochemical properties
      and in that it is located in the plastid. Differences and homologies can be
      traced back to the molecular level. The mature ALAD subunit, whose N-terminus was
      determined by automatic Edman degradation, is a protein of 367 amino acid
      residues and has a Mr of 40,132. This figure is in the range of molecular weights
      of non-plant ALADs. The active centre is highly conserved and the same is true
      for the ion-binding domain, except that 4 cysteines of the non-plant enzymes
      (binding Zn2+) have disappeared and a total of 6 aspartic acids meets the demands
      of Mg(2+)-binding. However, there are more distinct differences. Apart from a
      transit sequence of 56 amino acids targeting the plastid, the N-terminal part of
      the mature plant enzyme differs considerably from non-plant ALAD enzymes. It is
      rich in prolines and hydroxylated amino acids. The apparent Mr on SDS-PAGE is
      45,000 or higher, but up to now posttranslational modifications have not been
      found.

PMID- 1351730
TI  - CD8+ CD11+ suppressor cells in HIV-infected asymptomatic patients: effect on HIV
      specific cytotoxicity.
AB  - CD3+CD8+CD11+ cells were present in the peripheral blood of patients infected
      with asymptomatic human immunodeficiency virus (HIV) in higher percentage (10
      20%) than in normal individuals (3-5%) in this study. These cells, through the
      release of soluble factors, significantly suppressed the effector phase of anti
      HIV cytotoxic activities, both human leukocyte antigen (HLA)-class I or class II
      restricted, and nonrestricted. The effectors were CD8+CD11-, CD4+ T cells, and
      CD16+ cells for HLA-class I, class II restricted, and nonrestricted
      cytotoxicities, respectively. The soluble factors also inhibited natural killer
      cell activity. Thus, this effect was neither HLA-restricted nor antigen-specific.
      These CD3+CD8+CD11+ cells may be an important immunopathogenic factor in HIV
      disease.

PMID- 1351731
TI  - Transmitter release increases intracellular calcium in perisynaptic Schwann cells
      in situ.
AB  - Glial cells isolated from the nervous system are sensitive to neurotransmitters
      and may therefore be involved in synaptic transmission. The sensitivity of
      individual perisynaptic Schwann cells to activity of a single synapse was
      investigated, in situ, at the frog neuromuscular junction by monitoring changes
      in intracellular Ca2+ in the Schwann cells. Motor nerve stimulation induced an
      increase in intracellular Ca2+ in these Schwann cells; this increase was greatly
      reduced when transmitter release was blocked. Furthermore, local application of
      the cotransmitters acetylcholine and ATP evoked Ca2+ responses even in the
      absence of extracellular Ca2+. Successive trains of nerve stimuli or applications
      of transmitters resulted in progressively smaller Ca2+ responses. We conclude
      that transmitter released during synaptic activity can evoke release of
      intracellular Ca2+ in perisynaptic Schwann cells. This Ca2+ signal may play a
      role in the maintenance or modulation of a synapse. These data show that synaptic
      transmission involves three cellular components with both postsynaptic and glial
      components responding to transmitter secretion.

PMID- 1351732
TI  - Calcium waves in astrocytes-filling in the gaps.
AB  - Stimulus-evoked cellular responses are sometimes organized in the form of
      propagating waves of cytoplasmic Ca2+ increase. Ca2+ waves can be elicited in
      cultured astrocytes by the neurotransmitter glutamate; however, the propagation
      mechanism is unknown. Here, qualitative and quantitative features of propagation
      suggest that astrocytic Ca2+ waves are mediated by an intracellular signal that
      crosses intercellular junctions. The role of gap junctions in cell-cell Ca2+ wave
      propagation was specifically tested. Functional gap junctions were demonstrated
      using a noninvasive fluorescence recovery method and the gap junction blockers
      halothane and octanol. Gap junction closure prevented intracellular waves from
      propagating between cells without affecting the velocity of the intracellular
      wave itself. The pivotal role played by the gap junction creates the potential
      for dynamic changes in glial connectivity and long-range glial signaling.

PMID- 1351734
TI  - Ischemic Heart Disease 1991. 2nd Autumn Symposium on Coronary Artery Disease.
      Lisbon, October 10-12, 1991. Abstracts.

PMID- 1351733
TI  - Inhibition of quantal transmitter release in the absence of calcium influx by a G
      protein-linked adenosine receptor at hippocampal synapses.
AB  - Spontaneous miniature excitatory postsynaptic currents (MEPSCs) were recorded by
      whole-cell voltage-clamp techniques in cultured rat hippocampal pyramidal
      neurons. The specific adenosine A1 receptor agonist cyclopentyladenosine (CPA)
      reduced the frequency of MEPSCs without affecting their amplitude distribution or
      kinetic properties. This action was blocked by pretreatment of the cells with
      pertussis toxin. In the presence of divalent cation Ca2+ channel blockers, CPA
      was still effective in reducing the frequency of MEPSCs. It was shown that this
      effect cannot be explained by changes in basal Ca2+ influx. These results suggest
      that neurotransmitters that produce presynaptic inhibition at hippocampal
      synapses utilize several mechanisms, one of which may involve inhibition of some
      component of the quantal release apparatus that occurs independently of
      inhibition of Ca2+ influx.

PMID- 1351735
TI  - Bio-Recognition--International Industrial Biotechnology Conference. Montreal,
      Canada, 1-4 June 1992. Abstracts.

PMID- 1351736
TI  - Dexmedetomidine reduces intraocular pressure, intubation responses and
      anaesthetic requirements in patients undergoing ophthalmic surgery.
AB  - We studied the effects of a single i.v. dose of dexmedetomidine, a highly
      selective and specific alpha 2 adrenoceptor agonist, on intraocular pressure
      (IOP), haemodynamic and sympathoadrenal responses to laryngoscopy and tracheal
      intubation, and on anaesthetic requirements in ophthalmic surgery. Thirty ASA I
      II patients undergoing cataract surgery were allocated randomly to receive either
      dexmedetomidine 0.6 microgram kg-1 or saline placebo i.v. 10 min before induction
      of anaesthesia in a double-blind design. After dexmedetomidine there was a 34%
      (95% confidence interval (CI) 27-43%) reduction in IOP (P less than 0.001) and
      62% (CI 57-68%) decrease in plasma noradrenaline concentrations (P less than
      0.001). After intubation, maximum heart rate was 18% (CI 3-33%, P = 0.036) and
      the maximum IOP 27% (CI 11-43%, P = 0.005) less in the dexmedetomidine group
      compared with the patients treated with placebo. Within 10 min after intubation,
      maximum systolic and diastolic arterial pressures were also significantly (P =
      0.013 and P = 0.020) smaller in the dexmedetomidine group. The induction dose of
      thiopentone was smaller (23% (CI 20-26%) P = 0.012), and the use of isoflurane or
      fentanyl supplements during anaesthesia was less frequent in the dexmedetomidine
      group. The patients premedicated with dexmedetomidine recovered faster from
      anaesthesia (P = 0.042). These results suggest that dexmedetomidine may be a
      useful anaesthetic adjunct in ophthalmic surgery.

PMID- 1351737
TI  - Bradycardia and vecuronium: comparison with alcuronium during cholecystectomy.
AB  - We have compared the incidence of bradycardia in two groups of patients
      undergoing cholecystectomy. Twenty consecutive patients were allocated randomly
      to receive either vecuronium (n = 8) or alcuronium (n = 12) as part of a standard
      anaesthetic technique. Bradycardia was defined as a heart rate less than 50 beat
      min-1. Five episodes of bradycardia occurred with vecuronium and none with
      alcuronium (P less than 0.01).

PMID- 1351738
TI  - Paraphenylenediamine, a contact allergen, induces oxidative stress and ICAM-1
      expression in human keratinocytes.
AB  - In an investigation of the role of keratinocytes in the pre-immunological phase
      of contact allergy, we have studied the effect of paraphenylenediamine (PPD) on
      cell proliferation, membrane lipid peroxidation and the expression of the
      intercellular adhesion molecule 1 (ICAM-1). Because PPD undergoes rapid
      autoxidation in the culture medium, the effect of PPD-modified medium on
      keratinocyte proliferation and ICAM-1 expression was also examined. PPD at low
      concentrations (up to 10 micrograms/ml) and with low exposure times (0.5 h)
      enhanced keratinocyte proliferation, but at high concentrations and with longer
      exposure times resulted in cell stasis and toxicity. These effects and the
      enhanced membrane lipid peroxidation that was also observed can be ascribed to
      the production of superoxide and hydrogen peroxide by the autoxidation of PPD in
      the medium. At non-cytotoxic concentrations, PPD induced ICAM-1 expression on the
      keratinocytes. PPD-modified medium was also cytotoxic to the keratinocytes and
      induced ICAM-1 expression in non-cytotoxic concentrations. It appeared that
      superoxide and hydrogen peroxide were not responsible for the cytotoxicity. These
      results are consistent with the view that oxidative stress may be an essential
      part of the pre-immunological phase in the induction of allergic contact
      dermatitis.

PMID- 1351739
TI  - Tumours of Oddi: diagnosis and surgical treatment.
AB  - A retrospective review of 56 patients operated upon for tumours of Oddi was
      performed in order to determine optimal diagnostic and therapeutic procedures.
      Common presenting symptoms were jaundice (86%) and anemia (21%). Mean size of the
      tumour was 2.3 cm. Five tumours were benign and 51 were malignant. According to
      the classification of Martin, five were grade I: 10 grade II; 18 grade III; and
      18 grade IV. Forty-seven patients underwent resection of the tumour: three local
      excisions for small benign tumors, six ampullectomies (followed in three by a
      Whipples' procedure for recurrence) and 41 Whipples' procedures. The hospital
      mortality was 5.3%, minor complications appeared in 21%. The overall five years
      survival was 41%. It was 75% in grade I, 50% in grade II, 40% in grade III and
      10% in grade IV. The patients who received ampullectomies were alive with a
      follow-up of one, two and three years. All patients operated upon for a benign
      tumour were alive except one who died of cardiac failure. Ultrasonography and
      duodenoscopy are the most useful tests for the diagnosis of tumours of Oddi.
      Prognosis depends on the degree of infiltration of the duodenal wall and the
      presence of positive lymph nodes. Whipples' procedure is best but ampullectomy
      can be used in elderly or poor risk patients. Malignant tumours of the ampullary
      region are infrequent and reported to constitute between 0.02 and five percent of
      all cancers of the digestive tract. With wider application of endoscopic
      techniques, there has been an increasing interest in this group of tumours during
      recent years. In the literature tumours of Oddi are usually reported in the group
      of periampullary tumours, including tumours of the ampulla itself, duodenal wall
      surrounding the ampulla, the distal part of the common bile duct and head of the
      pancreas. We have wanted to distinguish specifically the tumours of the ampulla
      of Vater and have adopted the term tumour of Oddi introduced by Marchal and
      Hureau.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351740
TI  - Third Joint ESRA-ASRA Congress--XI Annual ESRA Congress. Brussels, Belgium, June
      9-12, 1992. Abstracts.

PMID- 1351741
TI  - Antigen binding thermodynamics and antiproliferative effects of chimeric and
      humanized anti-p185HER2 antibody Fab fragments.
AB  - The murine monoclonal antibody 4D5 (anti-p185HER2) inhibits the proliferation of
      human tumor cells overexpressing p185HER2 in vitro and has been "humanized"
      [Carter, P., Presta, L., Gorman, C. M., Ridgway, J. B. B., Henner, D., Wong, W.
      L. T., Rowland, A. M., Kotts, C., Carver, M. E., & Shepard, H. M. (1992) Proc.
      Natl. Acad. Sci. U.S.A. (in press)] for use in human cancer therapy. We have
      determined the antigen binding thermodynamics and the antiproliferative
      activities of chimeric 4D5 Fab (ch4D5 Fab) fragment and a series of eight
      humanized Fab (hu4D5 Fab) fragments differing by amino acid substitutions in the
      framework regions of the variable domains. Fab fragments were expressed by
      secretion from Escherichia coli and purified from fermentation supernatants by
      using affinity chromatography on immobilized streptococcal protein G or
      staphylococcal protein A for ch4D5 and hu4D5, respectively. Circular dichroism
      spectroscopy indicates correct folding of the E. coli produced Fab, and scanning
      calorimetry shows a greater stability for hu4D5 (Tm = 82 degrees C) as compared
      with ch4D5 Fab (Tm = 72 degrees C). KD values for binding to the extracellular
      domain (ECD) of p185HER2 were determined by using a radioimmunoassay; the delta H
      and delta Cp for binding were determined by using isothermal titration
      calorimetry. ch4D5 Fab and one of the humanized variants (hu4D5-8 Fab) bind
      p185HER2-ECD with comparable affinity (delta G degrees = -13.6 kcal mol
      1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351742
TI  - Ancestry of the 4-chlorobenzoate dehalogenase: analysis of amino acid sequence
      identities among families of acyl:adenyl ligases, enoyl-CoA
      hydratases/isomerases, and acyl-CoA thioesterases.
AB  - We have deduced the nucleotide sequence of the genes encoding the three
      components of 4-chlorobenzoate (4-CBA) dehalogenase from Pseudomonas sp. CBS-3
      and examined the origin of these proteins by homology analysis. Open reading
      frame 1 (ORF1) encodes a 30-kDa 4-CBA-coenzyme A dehalogenase related to enoyl
      coenzyme A hydratases functioning in fatty acid beta-oxidation. ORF2 encodes a 57
      kDa protein which activates 4-CBA by acyl adenylation/thioesterification. This 4
      CBA:coenzyme A ligase shares significant sequence similarity with a large group
      of proteins, many of which catalyze similar chemistry in beta-oxidation pathways
      or in siderophore and antibiotic synthetic pathways. These proteins have in
      common a short stretch of sequence, (T,S)(S,G)G(T,S)(T,E)G(L,X)PK(G,-), which is
      particularly highly conserved and which may represent an important new class of
      "signature" sequence. We were unable to find any proteins homologous in sequence
      to the 16-kDa 4-hydroxybenzoate-coenzyme A thioesterase encoded by ORF3. Analysis
      of the chemistry and function of the proteins found to be structurally related to
      the 4-CBA:coenzyme A ligase and the 4-CBA-coenzyme A dehalogenase supports the
      proposal that they evolved from a beta-oxidation pathway.

PMID- 1351743
TI  - Folding and assembly of the Escherichia coli succinyl-CoA synthetase
      heterotetramer without participation of molecular chaperones.
AB  - Succinyl-CoA synthetase of Escherichia coli (alpha 2B2 subunit structure) has
      been shown to fold and assemble without participation by molecular chaperones.
      Renaturation experiments showed that purified bacterial chaperone GroEL has no
      effect on the folding and assembly of the active tetrameric enzyme. When isolated
      35S-labeled alpha or beta subunits were incubated with GroEL in the absence of
      ATP, there was no complex formation between the subunits and GroEL. These in
      vitro results were confirmed by in vivo analysis of the folding and assembly of
      newly synthesized succinyl-CoA synthetase subunits. When expression of the
      subunits was induced in E. coli strains that bear GroEL or GroES temperature
      sensitive mutations, the assembly of active succinyl-CoA synthetase was not
      affected as the temperature was raised to 43 degrees C. These and other
      observations are discussed that indicate that folding and assembly of succinyl
      CoA synthetase may be independent of assistance by any chaperone.

PMID- 1351744
TI  - Characterization of human heart-infiltrating cells after transplantation. V.
      Suppression of donor-specific allogeneic responses by cloned T-cell lines
      isolated from heart biopsy specimens of patients after transplantation.
AB  - In vitro culture of heart biopsy specimens from patients after transplantation in
      media containing recombinant human interleukin-2 led to the exudation of host
      mononuclear-cell infiltrates. Cloned T-cell lines were prepared from such
      infiltrates and studied for donor-specific mixed lymphocyte reaction and
      cytotoxic T-lymphocyte activity. Although most T-cell clones (greater than 50%)
      showed donor-specific reactivity, a small but distinct frequency (2% to 10%) of
      the cloned T-cell lines did not proliferate against donor or third-party
      stimulator cells. Of interest was our finding that addition of these non-donor
      reactive cloned T-cell lines to autologous peripheral blood mononuclear cells
      markedly suppressed their donor-specific, but not third-party major
      histocompatibility complex, unrelated proliferative response and prevented the
      generation of donor, but not third-party, major histocompatibility complex
      unrelated cytotoxic T-lymphocyte function. The suppression was not secondary to
      lysis of donor stimulator cells, lysis of autologous donor-specific CD4+
      lymphoblasts, or by selective consumption of interleukin-2. The suppression was
      mediated at the initiation of sensitization (precursor cell level). These
      suppressor cells expressed CD3, CD8, CD45RO, and the alpha, beta T-cell receptor,
      but not CD4 or CD56. These cloned T-cell lines will provide unique reagents to
      study the molecular basis by which these cells exert their regulatory function.

PMID- 1351745
TI  - Characterization of human heart-infiltrating cells after transplantation. VI.
      Differences in the cytokines produced by individual CD4+ cloned T-cell lines with
      apparently identical antiidiotype-like reactivity.
AB  - Studies of cultures and cloned T-cell lines from mononuclear cell infiltrates in
      cardiac biopsy specimens have provided a unique resource to study the cellular
      basis of human organ allograft rejection. Our laboratory has previously shown
      that biopsy specimens placed on autologous donor MHC-class-II-specific cloned T
      cell lines from previous cardiac biopsies led to the isolation of cloned T-cell
      lines, which appeared to be functionally "antiidiotypic" in nature. Detailed
      functional analysis of such CD4+ individual antiidiotype-reactive cloned T-cell
      lines revealed that although some augmented the proliferative response of
      autologous idiotype-bearing cloned T-cell lines against donor stimulator cells,
      others markedly suppressed the proliferative response; thus, although each of
      these antiidiotype-like reactive cloned T-cell lines appears to specifically
      react with the same idiotype-bearing donor MHC-class-II-specific cloned T-cell
      line, they were functionally heterogeneous. Analysis of cytokines secreted by
      these individual clones showed that the antiidiotype-reactive cloned T-cell lines
      that suppressed the response of idiotype-bearing cells appear to secrete
      predominantly interferon gamma, whereas those antiidiotype-reactive cloned T-cell
      lines that augmented the response do not secrete interferon gamma but secrete
      interleukin-2, -4, and -6. These preliminary data suggest that differences in the
      predominant cytokines secreted by these individual antiidiotype-reactive cloned T
      cell lines may account for their functional differences.

PMID- 1351747
TI  - Glutamine affects glutamate metabolism in isolated rat kidney cortex
      mitochondria.
AB  - The active state respiration of isolated rat kidney cortex mitochondria with 10
      mM glutamate as single substrate is substantially increased by the addition of 10
      mM glutamine. This increase in respiration was accompanied by a higher
      transamination rate and was found to be insensitive to the selective inhibition
      of either the transamination or the desamination pathway of glutamate oxidation.
      These data can be explained by an approximately 2-fold elevated
      intramitochondrial glutamate concentration observed in the additional presence of
      glutamine.

PMID- 1351746
TI  - Enzyme inactivation by metal-catalyzed oxidation of coenzyme Q1.
AB  - Ubiquinol-1 in aerated aqueous solution inactivates several enzymes--alanine
      aminotransferase, alkaline phosphatase, Na+/K(+)-ATPase, creatine kinase and
      glutamine synthetase--but not isocitrate dehydrogenase and malate dehydrogenase.
      Ubiquinone-1 and/or H2O2 do not affect the activity of alkaline phosphatase and
      glutamine synthetase chosen as model enzymes. Dioxygen and transition metal ions,
      even if in trace amounts, are essential for the enzyme inactivation, which indeed
      does not occur under argon atmosphere or in the presence of metal chelators.
      Supplementation with redox-active metal ions (Fe3+ or Cu2+), moreover,
      potentiates alkaline phosphatase inactivation. Since catalase and peroxidase
      protect while superoxide dismutase does not, hydrogen peroxide rather than
      superoxide anion seems to be involved in the inactivation mechanism through which
      oxygen active species (hydroxyl radical or any other equivalent species) are
      produced via a modified Haber-Weiss cycle, triggered by metal-catalyzed oxidation
      of ubiquinol-1. The lack of efficiency of radical scavengers and the almost
      complete protection afforded by enzyme substrates and metal cofactors indicate a
      'site-specific' radical attack as responsible for the oxidative damage.

PMID- 1351748
TI  - Accumulation of transcripts coding for prion protein in human astrocytes during
      infection with human immunodeficiency virus.
AB  - The abnormal isoforms of the normal cellular prion protein (PrP), also termed
      Scrapie-associated fibril protein, are assumed to be one causative factor of
      spongiform encephalopathies. The mRNA of PrP contains stem-loop structures which
      are very similar to the human immunodeficiency virus-1 (HIV-1) cis-acting
      sequence TAR within the LTR; both structures contain the pentanucleotide CUGGG in
      the loop, and the uridine- and adenine-bulge in the stem. In this study, using
      purified HIV-encoded trans-activator, Tat, and HIV-1 TAR-RNA or PrP-mRNA
      containing the stem-loop structure, we demonstrate by use of gel-retardation and
      filter binding assays that Tat binds to TAR- and PrP-RNA with the dissociation
      constants of 2.9 or 37.0 nM, respectively, at a molar ratio of 0.7 mol of Tat to
      1 mol of RNA fragment. The Tat-RNA (TAR or PrP) complexes bind to protein(s) in
      the nuclear matrix, isolated from human astrocytes (glial fibrillary acidic
      protein positive brain cells). Infection of astrocytes with HIV-1 resulted in an
      increased level of PrP mRNA. The data presented led us to assume that certain
      sequences in the PrP mRNA might be targets for proteins acting in trans.

PMID- 1351749
TI  - [Is disclosure in radiology a medical or a legal problem?].

PMID- 1351750
TI  - Effect of beta-agonists on expression of calpain and calpastatin activity in
      skeletal muscle.
AB  - Administration of beta-adrenergic agonists to domestic species can lead to
      skeletal muscle hypertrophy, probably by reducing the rate of myofibrillar
      protein breakdown. Myofibrillar breakdown is associated with the calcium
      dependent proteinase system (calpains I,II and calpastatin) whose activity also
      changes during beta-agonist treatment. A number of growth trials using the
      agonists cimaterol and clenbuterol with cattle, sheep, chicken and rat are
      reported which suggest a general mechanism whereby beta-agonists reduce calpain I
      activity, but increase calpain II and calpastatin activity in skeletal muscle.
      Parallel changes in specific mRNAs indicate that changes in gene expression or
      stabilisation of mRNA could in part explain the changes in activity.

PMID- 1351751
TI  - Electrophysiological effects of atracurium and vecuronium on normal and
      denervated hearts.
AB  - Atracurium and vecuronium offer some advantages with respect to other
      nondepolarizing muscle relaxants. However, their administration has been
      associated with episodes of bradycardia and asystole, the mechanism of which has
      not yet been clarified. In an effort to analyze the effects of these drugs on
      automaticity, refractoriness, and conduction, 30 dogs underwent heterotopic heart
      transplantation to establish a model in which a normal heart (recipient) and a
      denervated heart (donor) could coexist. The electrophysiological studies included
      the determination of cycle length (CL), sinoatrial conduction time (SACT),
      antegrade and retrograde atrio-ventricular (A-V) node and ventricular block
      points (ABP and RBP), as well as effective antegrade and retrograde A-V node
      (ARPAVN and RRPAVN) and ventricular refractory periods (VRPs) in both hearts.
      These parameters were measured in a basal state and after injection of
      pancuronium (0.5 mg/kg) in 10 animals, atracurium (0.5 mg/kg) in another 10 dogs,
      and vecuronium (0.12 mg/kg) in the remaining animals. The results showed that
      pancuronium produced a tachycardia, significantly facilitated A-V conduction in
      the donor and the recipient hearts, and lowered the A-V node refractoriness in
      the donor organ, while atracurium and vecuronium induced no changes from the
      baseline values, either in normal or denervated hearts. Based on the results of
      this study, the episodes of sustained bradycardia reported in association with
      atracurium and vecuronium are attributed to the absence of antagonism of vagal
      stimuli provoked by pancuronium, and/or by surgical or anesthetic manipulations.

PMID- 1351752
TI  - Alpha 2-adrenergic agonists in cardiovascular anesthesia.
AB  - At this time, the unique attributes of alpha 2-agonists in anesthesia lie in
      their ability to blunt the adrenergic response to the stresses of major surgery,
      in patients in whom this response is especially undesirable, without incurring
      the penalty of respiratory depression that attends the use of opioids. It has
      become more and more apparent that sympathetic/adrenergic activation often has
      adverse consequences for patient morbidity and mortality, and modification of
      such activation by drugs may be a valuable option for the anesthesiologist.
      However, at present, the evidence supporting this statement is "soft," such as
      improved hemodynamic and metabolic stability. What must be done is to generate
      solid support in the form of well-designed outcome studies. The potential value
      of alpha 2-agonists is greatest in major surgery in brittle patients involving
      the risk of significant adverse outcome. There are plenty of adequate anesthesia
      regimens to cover lesser surgical interventions. In these cases, it is not the
      choice of a specific anesthetic agent or technique, but rather the competence and
      diligence of the anesthesiologist that is most important for outcome. In
      contrast, in major cardiovascular surgery in high-risk patients, the optimal
      anesthetic approach attains more importance, and is still undecided. The final
      consensus as to whether or not this optimal approach will include the use of
      alpha 2-adrenergic agonists will depend on the results of more extensive clinical
      investigations.

PMID- 1351753
TI  - Loss of heterozygosity on chromosome 16 in hepatocellular carcinoma.
AB  - In order to understand the molecular genetics of human hepatocellular carcinoma
      (HCC) a common chromosomal abnormality in HCC was examined using restriction
      fragment length polymorphism (RFLP) analysis. Sixty-eight HCC specimens were
      examined for loss of heterozygosity at 11 different chromosomal arms including
      1p, 5p, 11p, 11q, 13q, 14q, 15q, 16p, 16q, 18q, and 19q. Losses were not detected
      on chromosome 1, 5, 14, 15 or 19, and the frequencies of losses were low (11-19%)
      for chromosomes 11, 13 and 18. In contrast, loss of heterozygosity was frequently
      observed for three different loci on chromosome 16, the HBA locus at 16p13.3
      (22%), the MT2 locus at 16q21-22.1 (15%) and the HP locus at 16q22.1-22.2 (39%).
      There was no remarkable difference in the frequencies of loss of heterozygosity
      at these loci among HBV related HCC, HCV related HCC and neither virus (NBNC)
      related HCC. Thus, the results indicate that at least three different genetic
      abnormalities in chromosome 16 are commonly observed in various HCC, and that
      this chromosome may have some important role(s) in recessive genetic changes
      which generate this tumour.

PMID- 1351755
TI  - L-serine-O-phosphate blocks NMDA-evoked responses in the ampullae of Lorenzini of
      skates.
AB  - In the present study, we have shown by single afferent unit recording in the
      organs of Lorenzini that L-serine-O-phosphate (L-SOP) decreases the resting
      discharge frequency as well as electrically evoked responses. L-SOP in a
      concentration of 0.1-100 microM antagonizes responses induced by L-glutamate (L
      GLU) and N-methyl-D-aspartate (NMDA) and has no effect on the responses to
      application of kainate (KA) and quisqualate (Q). The results obtained confirm
      previous observations about the existence of NMDA receptors in the afferent
      synapse of the ampullae of Lorenzini.

PMID- 1351754
TI  - Ventral medulla stimulation increases blood pressure and spinal cord amino acid
      release.
AB  - Microdialysis in combination with HPLC and fluorescence detection was used to
      measure the release of endogenous amino acids from the region of the
      intermediolateral cell column of rat thoracic spinal cord in response to
      electrical stimulation of the rostral ventrolateral medulla (RVLM). Stimulation
      of the RVLM led to a marked rise in blood pressure (74 +/- 6 mm Hg) accompanied
      by an immediate increase in the release of glutamate (80%) and aspartate (50%).
      Small increases in the release of glycine and taurine were found, but there were
      no changes in alanine and serine release. These results suggest that the RVLM
      pressor pathway to the thoracic spinal cord may use, at least in part, excitatory
      amino acids as neurotransmitters, supporting previous pharmacological and
      neuroanatomical investigations of this bulbospinal pathway.

PMID- 1351756
TI  - Anxiolytic-like effects of a selective 5-HT1A agonist, S20244, and its
      enantiomers in mice.
AB  - The action of a selective 5-HT1A agonist S20244 and its two enantiomers (+)
      S20499 and (-)-S20500 were assessed in mice. The animals were confronted with a
      free exploratory test especially adapted to reveal behavioural sedation, and with
      a two-box light/dark choice situation validated for the detection of anti-anxiety
      agents. These drugs were found to have anxiolytic properties at low doses, like
      benzodiazepines. Furthermore, the drugs exhibited sedative effects at higher
      doses. These results closely resemble those we found after administration of two
      other 5-HT1A agonists, 8-OH-DPAT and MDL 73005EF (NeuroReport, 1, 267-270, 1990).

PMID- 1351757
TI  - Rat supraoptic neurons are resistant to glutamate neurotoxicity.
AB  - Magnocellular neurosecretory cells of the supraoptic nucleus (SON) are thought to
      be endogenously resistant to glutamate toxicity. In this study, we sought
      physiological and morphological evidence of this resistance in rats that received
      multiple peri-nuclear injections of ibotenate. In this preparation, ibotenate
      produced a large necrotic zone encompassing the SON but not within the nucleus
      itself. Extracellular recordings in vivo from 68 'spared' SON neurons from
      lesioned rats revealed normal patterns of electrical activity. Intracellular
      analysis in vitro from 13 'spared' SON neurons indicated that their intrinsic
      membrane properties, osmosensitivity and spontaneous synaptic activity did not
      differ significantly from that of controls. We conclude that SON neurons retain
      both a morphological and a physiological resistance to glutamate neurotoxicity.

PMID- 1351758
TI  - [Changes in the contents of peptides in the sensory-motor cortex of rats in
      response to post-stimulation convulsive discharges].

PMID- 1351760
TI  - [Morphobiochemical study of the liver in systemic endotoxinemia].
AB  - Dog liver in systemic endotoxemia induced by intravenous injection of E. coli
      lipopolysaccharide in 2 mg/kg dosage has been studied. Morpho- and pathogenetic
      characteristics of developing intoxication have been specified histologically and
      biochemically.

PMID- 1351759
TI  - [Neuromediator provision of the organs of immune system in benzpyrene
      intoxication].
AB  - The density of adrenergic innervation and relative content of catecholamines were
      investigated in rat lymphoid organs under different type of benzpyrene treatment.
      It was found that both ante- and postnatal influence of toxicant leads to a
      decrease of neurotransmitter providing of the thymus, spleen, mesenterial, iliac
      and popliteal lymph nodes. On the contrary, when mixed ante- and postnatal
      benzpyrene influence has place, the adrenergic innervation density and relative
      content of catecholamines are increased. We suppose that benzpyrene treatment of
      pregnant animals has specific "training" effect for monoaminergic systems of
      foetus and causes the increase of neurotransmitter providing of immunocompetent
      organs in conditions of repeat body and toxicant meeting.

PMID- 1351761
TI  - [Structural-functional characteristics of the renal endocrine system after alpha
      1 adrenoreceptor blockade].
AB  - Research Institute of Cardiology, Uzbek Health Ministry Structural and functional
      peculiarities of the renal juxtaglomerular and interstitial cells were studied
      after alpha 1-adreno-blockers were used. The endocrine cells were studied after a
      single and prolonged introduction of the agents. Administration of a single dose
      of the drugs led to hypergranulation in juxtaglomerular cells thus decreasing
      their functional activity and release of the granules from the cells. The
      interstitial cells function intensified. Prolonged administration of alpha 1
      adrenoblockers caused a degranulation process in the juxtaglomerular cells and a
      decrease in their protein-synthetizing structures, namely, renin synthesis, and
      elevation of synthetic process in the interstitial cells.

PMID- 1351762
TI  - Expression of selected human HOX-2 genes in B/T acute lymphoid leukemia and
      interleukin-2/interleukin-1 beta-stimulated natural killer lymphocytes.
AB  - Although the key role of human homeobox (HOX) genes in development is well
      established, their function in adult cells is still under scrutiny. We have
      analyzed, in normal adult blood cell subpopulations, acute lymphoid leukemia
      (ALL) cells lines, and primary blasts, the RNA expression of all HOX-2 cluster
      genes (5'-2.5, 2.4, 2.3, 2.2, 2.1, 2.6, 2.7, 2.8, 2.9, 3') and nine genes in the
      HOX-1, -3, and -4 cluster by Northern blotting, RNAse protection, and/or reverse
      transcriptase polymerase chain reaction (RT-PCR). The analyzed HOX-1, -3, and -4
      genes were never expressed in all tested cell populations. Natural killer (NK)
      cells activated in interleukin-2 (IL-2)/IL-1 beta-treated cultures exhibit a
      gradually increasing, abundant expression of three HOX-2 genes (2.2, 2.6, 2.8),
      while three other genes (2.3, 2.1, 2.7) are expressed at a lower level at late
      culture times. However, no HOX-2 gene is expressed in quiescent lymphocytes (NK,
      B and T [T-cell receptor (TCR) alpha/beta, gamma/delta lymphocytes, thymocytes]
      cells), granulocytes, and monocytes. In B- and T-ALL cell lines, HOX-2 genes are
      expressed according to different patterns: (1) widespread transcription (seven of
      nine genes, including 2.3 and 2.6) in the Peer line bearing the TCR gamma/delta;
      (2) expression of 2.5, 2.2, and 2.6 in the SEZ 627 line, which derives from an
      HTLV-1+ T-helper leukemia; (3) transcription of 2.3 and 2.6 in both the T-ALL CEM
      line and four B-ALL lines (interestingly, CALLA- B-ALL lines are constantly
      2.3/2.6 RNA+); (4) no HOX-2 gene expression was detected in one T- and two B-ALL
      lines. Primary blasts from five T- and five pre-B-ALL showed selective expression
      of one or more HOX-2 genes, namely 2.5, 2.2, 2.6, and 2.7. Our data are
      compatible with the hypothesis that selected HOX-2 genes play a role in the IL
      2/IL-1 beta-induced activation and/or proliferation of normal NK lymphocytes and
      possibly in the oncogenetic process of some T- and B-ALL.

PMID- 1351763
TI  - Formation of a hyperdiploid karyotype in childhood acute lymphoblastic leukemia.
AB  - Hyperdiploidy with greater than or equal to 50 chromosomes is a frequent and
      distinct karyotypic pattern in the malignant cells of children with acute
      lymphoblastic leukemia. To understand better the mechanism of formation of the
      hyperdiploid karyotype, we studied 15 patients using 20 DNA probes that detect
      restriction fragment length polymorphisms. We first examined disomic chromosomes
      for loss of heterozygosity. Two patients had widespread loss of heterozygosity on
      all informative disomic chromosomes, and represent cases of near-haploid leukemia
      in which the chromosomes doubled. One other patient had loss of heterozygosity
      limited to chromosome 3; in this patient all of seven other informative disomic
      chromosomes retained heterozygosity. Loss of heterozygosity was not detected in
      the remaining 12 patients on a total of 87 informative disomic chromosomes. We
      then examined tetrasomic chromosomes for parental dosage. Of the 13 patients in
      whom widespread loss of heterozygosity was not present, 11 patients had tetrasomy
      21; 10 of 11 (91%) had an equal dose of maternal and paternal alleles on
      chromosome 21 and only 1 of 11 (9%) had an unequal dose of parental alleles in a
      3:1 ratio. These results suggest that the hyperdiploid karyotype usually arises
      by simultaneous gain of chromosomes from a diploid karyotype during a single
      abnormal cell division, and occasionally by doubling of chromosomes from a near
      haploid karyotype. The hyperdiploidy in cases without widespread loss of
      heterozygosity is not caused by stepwise or sequential gains from a diploid
      karyotype or by losses from a tetraploid karyotype; the former should result in a
      3:1 parental dosage for 67% of tetrasomic chromosomes (9% observed) and the
      latter should result in loss of heterozygosity for 33% of disomic chromosomes (1%
      observed). Additional studies of the molecular basis for this leukemia subtype
      are warranted.

PMID- 1351764
TI  - Uniparental disomy: a novel mechanism for thalassemia major.

PMID- 1351766
TI  - Evolution of zidovudine dosing.

PMID- 1351765
TI  - [Epidemiological characteristics of HIV-2 infection in Africa].

PMID- 1351767
TI  - Severe chronic diarrhea secondary to celiprolol.

PMID- 1351768
TI  - A young female case of polyarteritis nodosa strongly suspected by typical
      angiographic findings which improved rapidly after prednisolone and
      cyclophosphamide therapy.
AB  - A 16-year-old girl was admitted with the complaints of headache, chest pain, low
      abdominal pain and left hemi-numbness. Her blood pressure was high and plasma
      renin activity and aldosterone levels were elevated. Renal angiography revealed
      vascular stenoses and microaneurysms although the renal artery and its main
      branches were not involved. Polyarteritis nodosa (PN) was strongly suspected and
      oral prednisolone and intravenous pulse therapy of cyclophosphamide were started.
      The second renal angiography which was performed 11 days after the therapy was
      started, showed marked improvement of vascular lesions. This is a case which
      suggests that the angiographic findings of PN can improve very rapidly with
      therapy.

PMID- 1351769
TI  - A set of anonymous DNA clones as markers for mouse gene mapping.

PMID- 1351770
TI  - The development and characterization of a natural killer cell-resistant human
      renal cell carcinoma cell line.
AB  - Natural killer (NK) cells are large granular lymphocytes that are able to
      recognize and lyse a broad spectrum of transformed cells. We report one approach
      to identify NK surface recognition molecules on human tumor targets. A cloned
      renal cell carcinoma (RCC) cell line, 5117GB, sensitive to NK activity, was made
      NK-resistant (5117GBT) by exposure to peripheral blood mononuclear cells. Both
      cell lines were found to be sensitive to lymphokine-activated killer cells. Both
      5117GB and 5117GBT were positive for laminin (25-33%), CD2 (LFA-3 receptor, 95
      98%), CD54 (ICAM-1, 99-100%) and CD58 (LFA-3, 100%). 5117GB was positive for HLA
      ABC while 5117GBT lost detectable HLA-ABC. F(ab')2 fragments of HLA-ABC were not
      able to block NK-mediated cytotoxicity of 5117GB. We identified 6 murine
      monoclonal antibodies that preferentially bind either to sensitive or resistant
      RCC cells. The role of each of the antigens recognized by these antibodies in NK
      mediated lysis is being explored. The development of NK-sensitive and NK
      resistant human solid tumor cell lines may allow further exploration of surface
      molecules involved with NK binding and lysis.

PMID- 1351771
TI  - 5th International Conference on Cell-Mediated Calcification and Matrix Vesicles.
      Hilton Head, South Carolina, November 16-20, 1991.

PMID- 1351772
TI  - Tyrosine hydroxylase expression in non-catecholaminergic cells in cerebellar
      cultures.
AB  - Organotypic cerebellar cultures, some with incorporated portions of brainstem,
      were immunostained after 12-19 days in vitro with three different antibodies to
      tyrosine hydroxylase. Similar cultures were reacted with glyoxylic acid and
      examined for catecholamine histofluorescence. Locus coeruleus and other
      subcortical neurons were positive for tyrosine hydroxylase, as were Purkinje
      cells and outgrowth zone astrocytes. By contrast, only locus coeruleus neurons
      and their axons exhibited catecholamine histofluorescence after reaction with
      glyoxylic acid. These results confirm previously reported in vivo developmental
      studies indicating that tyrosine hydroxylase can be expressed in the absence of
      its normal biosynthetic products, and suggest that tyrosine hydroxylase cannot be
      considered to be a specific marker for catecholaminergic neurons in vitro, as
      well as during development in vivo.

PMID- 1351773
TI  - Glutamate, NMDA and NMDA receptor antagonists: cardiovascular effects of
      intrathecal administration in the rat.
AB  - Selected excitatory amino acids and antagonists were tested for their effects on
      arterial pressure and heart rate when administered intrathecally at the second
      (T2) or ninth (T9) thoracic spinal levels in urethane-anesthetized Sprague-Dawley
      rats with spontaneous or artificial respiration. Intrathecal administration of
      glutamate (1 mumol) and N-methyl-D-aspartic acid (NMDA; 2 nmol) at T9 increased
      arterial pressure and heart rate. The response began within 1 min, peaked at 2-3
      min and persisted for 8-15 min. The maximum changes were 20-25 mm Hg for arterial
      pressure and 40-50 beats/min for heart rate. These responses were prevented by
      systemic administration of hexamethonium (10 mg/kg). Responses to administration
      of NMDA at the two spinal levels were essentially the same. Effects elicited by
      NMDA but not by glutamate were blocked by pretreatment with the NMDA receptor
      antagonists, D,L-2-amino-5-phosphonovaleric acid (APV; 10 nmol, intrathecal
      administration) and ketamine (7 mg/kg, i.v.). Intrathecal administration of APV
      (10, 50 and 200 nmol) at T2 produced dose-dependent decreases in arterial
      pressure without changing heart rate. The results support the hypothesis that
      NMDA receptors are involved in regulation of sympathetic output at the spinal
      level. They also indicate that in this preparation there is a tonic activation of
      NMDA receptors in sympathetic pathways to the vessels but not to the heart.
      Finally, the persistence of the response to glutamate in the presence of NMDA
      receptor antagonists suggests the involvement of non-NMDA receptors in spinal
      control of sympathetic output.

PMID- 1351774
TI  - Peptides for calling? An immunohistochemical study of the avian n.
      intercollicularis.
AB  - We used two phylogenetically distant avian species (dark-eyed junco, hyemalis,
      Passeriformes; domestic pigeon, Columba livia, Columbiformes) to determine the
      immunocytochemical distribution of opioid (leucine-enkephalin, dynorphin B) and
      non-opioid (adrenocorticotropic hormone) peptides in the n. intercollicularis
      (ICo), a midbrain region which plays a central role in the control of
      vocalizations. We found that, in both species, the peptides under study are
      present as fibers and terminal-like structures, and are similarly distributed.
      The n. dorsomedialis intercollicularis division contains much less
      immunoreactivity than the rest of the ICo. Based on this and previous studies, we
      propose that opioid peptides, possibly transported from the preoptic and
      hypothalamic regions of the diencephalon to the ICo, regulate vocal behavior by
      altering respiratory function rather than syringeal mechanisms.

PMID- 1351775
TI  - The non-NMDA antagonists, NBQX and GYKI 52466, protect against cortical and
      striatal cell loss following transient global ischaemia in the rat.
AB  - The cerebroprotective action of non-NMDA receptor blockade has been assessed in a
      model of transient global ischaemia using NBQX, 2,3-dihydro-6-nitro-7-sulphamoyl
      benzo(F)quinoxaline, and GYKI 52466, 1-(amino-phenyl)-4-methyl-7,8-methylendioxy
      5H-2,3-benzodiazepine. HCl. In Wistar rats, prior cauterisation of the vertebral
      arteries was followed by occlusion of the common carotid arteries for 20 min,
      with a 7 day survival period before histological evaluation. NBQX, 40 mg/kg, or
      GYKI 52466, 40 mg/kg, was administered intravenously starting directly after the
      end of carotid occlusion and ending 3 h later. Both compounds produced
      significant protection against selective cell loss in the striatum and cortex.
      Less consistent changes were seen in the hippocampus; protection by NBQX was
      significant in CA3 but neither compound produced significant protection in CA1.
      This pattern of protection is interpreted in terms of a blockade of glutamate's
      action at non-NMDA receptors limited to the initial 3 h of reperfusion.

PMID- 1351776
TI  - C-terminal tail of beta-adrenergic receptors: immunocytochemical localization
      within astrocytes and their relation to catecholaminergic neurons in N. tractus
      solitarii and area postrema.
AB  - beta-Adrenergic receptors (beta AR) in the medial nuclei of tractus solitarii (m
      NTS) and area postrema (AP) may bind to catecholamines released from neurons,
      whereas only the AP has fenestrated capillaries allowing access to circulating
      catecholamines. Since varied autonomic responses are seen following beta AR
      activation of the dorsal vagal complex, including the m-NTS and AP, we
      hypothesized that there might be a cellular basis for varied responses to beta AR
      stimulation that depends on the differential access to circulating
      catecholamines. Therefore, we comparatively examined the ultrastructural
      localization of the beta AR in relation to catecholaminergic neurons in these
      regions. An antibody directed against the C-terminal tail (amino acids 404-418)
      of hamster beta-adrenergic receptor (beta AR404) was used in this study. The
      localization of beta AR404 was achieved by the avidin-biotin peroxidase complex
      (ABC) technique in combination with a pre-embed immunogold labeling method to
      localize tyrosine hydroxylase (TH), the catecholamine-synthesizing enzyme. Within
      m-NTS and at subpostremal border, labeling for beta AR404 was evident along the
      intracellular surface of plasma membranes of small, apparently distal, astrocytic
      processes. Astrocytic processes with beta AR404-immunoreactivity formed multiple,
      thin lamellae around TH-labeled and non-TH neuronal cell bodies and dendrites.
      beta AR404-immunoreactive astrocytes also extended end-feet around blood vessels
      and surrounded groups of axon terminals that were directly juxtaposed to each
      other. Some, but not all, of these axons demonstrated TH-immunoreactivity. Fewer
      beta AR404-immunoreactive astrocytes were detected in AP, regardless of their
      proximity to catecholaminergic processes or blood vessels. The present astrocytic
      localization of beta AR404, together with the earlier, neuronal localization of
      beta AR's third intracellular loop, suggest that the beta AR may be substantially
      different between neurons and astrocytes. The regional difference in the
      prevalence of beta AR404-immunoreactive astrocytes suggests that these receptive
      sites may either: (i) be preferentially activated by catecholamines released from
      terminals rather than circulating catecholamines; or (ii) be down-regulated in AP
      due to blood-born substances, such as catecholamines. The extensive localization
      of beta AR in the border between m-NTS and AP also suggests that
      catecholaminergic activation of these astrocytes may dictate the degree of
      diffusion of catecholamines which are of neuronal or vascular origin. The
      specific localization of beta AR404-immunoreactivity to the more distal portions
      of astrocytes suggests the possibility that astrocytes have restrictive
      distributions of beta AR and that the beta-adrenergic activation lead to
      morphological or chemical changes that are also localized to the distal portions
      of astrocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1351777
TI  - The influence of opioids on local cerebral glucose utilization in the newborn
      pig.
AB  - Topical methionine enkephalin, leucine enkephalin, and dynorphin (10(-6)M)
      previously have been observed to produce prominent pial arteriolar dilation.
      Dilation to these opioids could be caused directly by opioids acting on vascular
      receptors, or indirectly, as a consequence of increased metabolism. Therefore, we
      examined this possibility by determining the influence of opioids on cerebral
      glucose utilization in piglets with closed cranial windows using the
      [14C]deoxyglucose method. Qualitatively, the autoradiographic images expressed as
      a change in relative optical density from vehicle were unchanged by these
      opioids. Quantitatively, the opioids similarly had no effect on cerebral glucose
      utilization (53 +/- 5, 70 +/- 8, 63 +/- 5, and 52 +/- 3, mumol.100 g-1.min-1 for
      vehicle, methionine enkephalin, leucine enkephalin, and dynorphin, respectively).
      In contrast, topical glutamate (10(-3) M) produced similar dilation but increased
      cerebral glucose utilization (41 +/- 3 vs 89 +/- 8 mumol.100 g-1.min-1 for
      vehicle and glutamate, respectively). Therefore, these opioids do not appear to
      produce vascular effects through a change in cerebral metabolic utilization of
      glucose.

PMID- 1351778
TI  - Hypothalamic corticotropin-releasing hormone and opioid peptide neurons:
      functional changes after adrenalectomy and/or castration.
AB  - The influences of short- and long-term castration and adrenalectomy (or both)
      upon corticotropin-releasing hormone (CRH) mRNA levels, CRH peptide levels, and
      endogenous opioid peptide (EOP) content in the hypothalamus, and basal and CRH
      stimulated EOP release in vitro, were examined. Gonadal and adrenal steroids
      regulated the function of these hypothalamic peptidergic systems in terms of
      peptide synthesis, storage pools, and secretion. The steroids were also found to
      alter the sensitivity of EOPergic neurons to CRH. In some cases, evidence was
      obtained for an interaction between gonadal and adrenal steroids in determining
      neuronal function (seen as additive or counteractive effects). A finding of major
      importance was that the response of these peptidergic systems was markedly
      influenced by the duration of steroid deprivation, the results of chronic
      treatment often being opposite to those of acute treatment. Lastly, inspection of
      the data on peptide synthesis, storage and release, revealed that there was no
      simple relationship between these three parameters even within a single type of
      peptidergic neuron.

PMID- 1351779
TI  - Anticonvulsants inhibit rat neuronal somatostatin release.
AB  - Somatostatin (SRIF), a peptide widely distributed in the central nervous system,
      has been implicated in the genesis of seizure activity in a number of animal
      models of epilepsy. We examined the effects of the anticonvulsants, phenytoin,
      carbamazepine and diazepam, on the release of SRIF from dispersed adult rat
      neuronal cells in short-term culture. Each of these agents caused dose-dependent
      inhibition of ouabain-stimulated SRIF release in a well-characterized
      hypothalamic dispersed cell system. We also examined the effects of phenytoin on
      SRIF release from dispersed rat cortical cells and inhibition of stimulated SRIF
      secretion was again observed. These findings support the hypothesis that the
      inhibition of neuronal SRIF release may represent a pharmacological mechanism of
      action of anticonvulsants.

PMID- 1351780
TI  - Role of N-methyl-D-aspartate receptors in dopamine D1-, but not D2-, mediated
      changes in striatal and accumbens neurotensin systems.
AB  - The role of N-methyl-D-aspartate (NMDA) receptors in specific D1 and D2
      regulation of striatal and accumbens neurotensin (NT) systems was investigated.
      As demonstrated previously, stimulation of D1 receptors with multiple
      administrations of SKF 38393 significantly increased striatal and accumbens NT
      content to approximately 145% of control. These responses were completely blocked
      by coadministration of the non-competitive NMDA antagonist, MK 801. Previous
      studies have documented that D2 receptors tonically regulate striatal NT systems.
      Thus, multiple doses of sulpiride, a D2 antagonist, increased striatal NT content
      to 167% of control while quinpirole, a D2 agonist, decreased striatal NT content
      to 58% of control. MK 801 did not alter either striatal NT response to D2
      manipulation. As previously reported, levels of accumbens NT changed only in
      response to D2 blockade and not to D2 stimulation. Thus, sulpiride increased
      accumbens NT content to 138% of control; this was not blocked by the
      coadministration of MK 801. NT content also significantly increased after
      stimulation of glutamate receptors with NMDA. To determine if D1 receptors
      participate in this NMDA-mediated change, the D1 antagonist SCH 23390 was
      coadministered. Blockade of D1 receptors did not significantly alter the response
      of striatal NT systems to NMDA. However, in both striatum and nucleus accumbens,
      the NMDA effect on NT systems appeared to be lessened. In summary, expression of
      D1-, but not D2-mediated changes in striatal and accumbens NT systems are
      markedly dependent on NMDA receptor activity. In comparison, expression of the
      NMDA-mediated changes in the same NT systems do not appear to be as dependent on
      D1 receptor activity.

PMID- 1351782
TI  - Inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in rat
      hippocampus by L-aspartate-beta-hydroxamate.
AB  - The effect of a series of glutamate uptake inhibitors was tested on ibotenate
      stimulated phosphoinositide hydrolysis. The pharmacological profile of the
      inhibitory effect of these compounds on the ibotenate response was quite
      different from that on glutamate uptake. Aspartate-beta-hydroxamate was the most
      potent compound with the L-isomer (IC50 11 +/- 2 microM) being considerably more
      potent than the D-isomer (IC50 104 +/- 12 microM). The effect of the L-aspartate
      beta-hydroxamate was found to be specific for ibotenate and quisqualate
      stimulated phosphoinositide hydrolysis; this compound did not affect hydrolysis
      stimulated by carbachol, K+ or sodium fluoride. The inhibition of the ibotenate
      response was found to involve a non-competitive and irreversible mechanism.

PMID- 1351781
TI  - Effects of chronic treatment with selective agonists on the subtypes of dopamine
      receptors.
AB  - The effects of chronic administration of selective dopaminergic agonists on D1
      and D2 receptor density, affinity and function were measured in Sprague-Dawley
      rats. Animals received daily injections (i.p.) of the D1-selective agonist SKF
      38393 (10 mg/kg), the D2-selective agonist quinpirole (1 mg/kg), SKF-38393 plus
      quinpirole, or saline for 14 days. Quantitative autoradiographic analysis
      revealed that the density of D2 receptors was decreased following chronic
      treatment with quinpirole alone or in combination with SKF-38393 whereas SKF
      38393 by itself had no effect on this receptor. In contrast, the density of D1
      receptors was increased following treatment with SKF-38393. Although quinpirole
      by itself had no effect on D1 receptors, co-administration with SKF-38393
      attenuated the up-regulation of D1 receptors produced by SKF-38393 in the caudate
      putamen and nucleus accumbens but not in the substantia nigra. The up-regulation
      of D1 receptors in response to chronic SKF-38393 may be attributed to the partial
      agonist properties of SKF-38393 which may not provide sufficient D1 receptor
      stimulation to down-regulate the receptor. Quinpirole-induced hypothermia and SKF
      38393-induced hyperthermia were measured before and after chronic agonist
      treatments to examine the effects of these treatments on thermoregulatory
      functions mediated by each receptor subtype. Treatment with quinpirole or
      quinpirole plus SKF-38393 resulted in desensitization of quinpirole-induced
      hypothermia, whereas treatment with SKF-38393 alone had no effect. All of the
      chronic treatments produced sensitization of SKF-38393-induced hyperthermia.
      Since not all treatments result in an increase in the density of D1 receptors, up
      regulation of D1 receptors is not the sole mechanism for this sensitization.

PMID- 1351784
TI  - Hippocampal neuronal responsiveness to NMDA agonists and antagonists in the adult
      rat neonatally treated with MK-801.
AB  - Long-lasting effects of neonatal interference with N-methyl-D-aspartate (NMDA)
      receptors were investigated by measuring responses to micro-iontophoretically
      applied NMDA agonists/antagonist in hippocampal neurons of the adult rat. Rat
      pups were chronically treated with MK-801 from postnatal day 8 through 19 and
      tested at postnatal day 70-100. CA1 cell responses to glutamate were not affected
      by the neonatal treatment. However, a stronger suppression of the NMDA evoked
      response by the NMDA site antagonist amino-5-phosphonovalerate (APV) was
      measured, suggesting a long-lasting configurational change of the NMDA receptor.
      The NMDA evoked responses were equally strong suppressed by MK-801 in both
      groups, suggesting that channel sites were not affected by this treatment.

PMID- 1351783
TI  - The antidepressants fluoxetine, idazoxan and phenelzine alter corticotropin
      releasing hormone and tyrosine hydroxylase mRNA levels in rat brain: therapeutic
      implications.
AB  - Various classes of antidepressant drugs with distinct pharmacologic actions are
      differentially effective in the treatment of classic melancholic depression-
      characterized by pathological hyperarousal and atypical depression--associated
      with lethargy, hypersomnia, and hyperphagia. All antidepressant agents exert
      their therapeutic efficacy only after prolonged administration. In situ
      hybridization histochemistry was used to examine in rats the effects of short
      term (2 weeks) and long-term (8 weeks) administration of 3 different classes of
      activating antidepressant drugs which tend to be preferentially effective in
      treating atypical depressions, on the expression of central nervous system genes
      thought to be dysregulated in major depression. Daily administration (5 mg/kg,
      i.p.) of the selective 5-hydroxytryptophan (5-HT) reuptake inhibitor fluoxetine,
      the selective alpha 2-adrenergic receptor antagonist idazoxan, and the
      nonspecific monoamine oxidase A and B inhibitor phenelzine increased tyrosine
      hydroxylase mRNA levels by 70-150% in the locus coeruleus after 2 weeks of drug
      and by 71-115% after 8 weeks. The 3 drugs decreased corticotropin-releasing
      hormone mRNA levels by 30-48% in the paraventricular nucleus of the hypothalamus.
      The decreases occurred at 8 weeks but not at 2 weeks. No consistent change in
      steroid hormone receptor mRNA levels was seen in the hippocampus with the 3
      drugs, but fluoxetine and idazoxan increased the level of mineralocorticoid
      receptor (MR) and glucocorticoid receptor (GR) mRNA, respectively, after 8 weeks
      of drug administration. Proopiomelanocortin (POMC) mRNA levels in the anterior
      pituitary and plasma adrenocorticotropic-hormone (ACTH) levels were not altered
      after 2 or 8 weeks of drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351785
TI  - A dose-dependent increase of Tau immunostaining is produced by glutamate toxicity
      in primary neuronal cultures.
AB  - Neuronal degeneration was produced in primary cultures by glutamate exposure and
      the modifications of Tau immunoreactivity were analysed in degenerating neurons.
      After 8-12 days of culture, glutamate was applied at different concentrations
      (50, 100, 200 and 500 mumol) in a Na(+)- and Mg(2+)-free solution containing
      calcium. Prior to and 12 hours after glutamate exposure cell death was defined by
      cell counting in each dish. After fixation, neurons were processed for
      immunocytochemistry using a Tau2 monoclonal antibody and a Tau polyclonal
      antibody (Sigma). Tau immunostaining was scored by a blind count of
      immunoreactive cells and a semi-quantitative evaluation. The results show that
      the number of labelled neurons and the magnitude of neuronal immunolabelling are
      both related to the glutamate concentration. Our findings indicate that glutamate
      induces a dose-dependent increase of Tau immunoreactivity directly related to its
      cellular action on neuronal cells.

PMID- 1351786
TI  - Presynaptic site of action underlying the ethanol-induced inhibition of
      norepinephrine release evoked by stimulation of N-methyl-D-aspartate (NMDA)
      receptors in rat cerebral cortex.
AB  - Rat brain cortex synaptosomes pre-incubated with [3H]norepinephrine were used (1)
      to provide evidence that part of the NMDA receptors mediating stimulation of
      norepinephrine (NE) release are located on the noradrenergic varicosities
      themselves, (2) to characterize these receptors and (3) to examine whether
      ethanol specifically inhibits the NMDA-evoked NE release via a presynaptic site
      of action. In synaptosomes superfused with Mg(2+)-free Krebs-Henseleit solution,
      NMDA (2-min exposure) stimulated tritium overflow in a concentration- and glycine
      dependent manner. The stimulatory effect of NMDA was not altered by tetrodotoxin
      but was abolished by omission of Ca2+ from the superfusion fluid and was
      considerably reduced in the presence of 1.2 mM Mg2+. DL-(E)-2-Amino-4-methyl-5
      phosphono-3-pentanoic acid (CGP 37849; a competitive NMDA receptor antagonist)
      produced a parallel shift of the concentration-response curve for NMDA to the
      right, whereas dizocilpine (MK-801; an antagonist at the phencyclidine, PCP,
      recognition site of the NMDA-gated ion channel) reduced the maximum effect of
      NMDA. Ethanol inhibited the NMDA-evoked tritium overflow in a concentration
      dependent manner. In contrast, in synaptosomes superfused with Ca(2+)-free Krebs
      Henseleit solution containing 15 mM K+ throughout, ethanol did not affect the
      tritium overflow evoked by 2 min introduction of 75 microM Ca2+ into the
      superfusion fluid. This Ca(2+)-evoked overflow was also not altered by
      tetrodotoxin and dizocilpine, but was inhibited by the inorganic Ca2+ channel
      antagonist Cd2+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351787
TI  - Capsaicin-sensitive nonadrenergic and noncholinergic depressor response to spinal
      cord stimulation in the pithed rat.
AB  - The effects of capsaicin on nonadrenergic, noncholinergic depressor responses to
      spinal cord stimulation were studied in pithed rats. Mean blood pressure (MBP was
      maintained at a level of 100 mmHg by continuous infusion of methoxamine and
      hexamethonium to block autonomic outflow. Electrical stimulation of the lower
      thoracic region (T9-12) via a pithing rod produced a frequency (1-8 Hz)-dependent
      fall in elevated MBP. The depressor response was abolished by tetrodotoxin,
      whereas atropine, propranolol, and cimetidine plus pyrilamine did not affect the
      response. Capsaicin treatment abolished the depressor response. These results
      suggest that spinal cord stimulation causes neurogenic vasodilation which is
      mediated by capsaicin-sensitive nonadrenergic and noncholinergic vasodilator
      nerves.

PMID- 1351788
TI  - Carbachol-induced theta-like activity in entorhinal cortex slices.
AB  - The present study was conducted for two purposes: the first was to evaluate
      whether activation of cholinergic receptors of the entorhinal cortex in vitro
      (complete deafferentation) with carbachol (100 microM) was capable of producing
      theta (theta)-like slow activity. The second purpose was to determine whether
      carbachol-induced slow waveforms were mediated by muscarinic or nicotinic
      receptors. We demonstrated that carbachol was capable of producing theta-like
      slow activity. This activity was not altered by nicotinic antagonists, (+)
      tubocurarine and hexametonium. Atropine and scopolamine, in contrast, completely
      blocked in vitro induced slow waves, indicating entorhinal muscarinic receptors
      to be actively involved in the mechanism generating cholinergic theta rhythm.

PMID- 1351789
TI  - Presynaptic GABAB receptor activation attenuates synaptic transmission to rat
      sympathetic preganglionic neurons in vitro.
AB  - Intracellular recordings were made from sympathetic preganglionic neurons (SPNs)
      in transverse neonate rat spinal cord slices. Superfusion of gamma-aminobutyric
      acid (GABA; 25-100 microM) or (-)-baclofen (1-30 microM) consistently attenuated
      the excitatory postsynaptic potentials (EPSPs) evoked by stimulation of dorsal
      rootlets or lateral funiculus, without causing a significant change of the
      resting membrane potential and input resistance of the SPNs or of the
      depolarizations induced by pressure applications of glutamate; the IC50 for
      baclofen was 2.5 microM. When superfused at a higher concentration (greater than
      or equal to 500 microM) or ejected by pressure GABA caused a bicuculline
      sensitive membrane hyperpolarization. The enantiomer (+)-baclofen (10-50 microM)
      and the GABAA agonist muscimol (1-10 microM) had no significant effect on the
      EPSPs. The GABAB receptor antagonist 2-hydroxy-saclofen caused a 10 fold
      rightward shift of the baclofen dose-response curve, whereas the GABAA receptor
      antagonist bicuculline (10-50 microM) was ineffective. Glycine had no significant
      effects on the EPSPs in the concentrations (10-100 microM) tested here. The
      results indicate that of the two putative inhibitory transmitters in the spinal
      cord GABA but not glycine depresses EPSPs evoked in the rat SPNs by acting on
      presynaptic GABAB receptors, the activation of which results in a reduction of
      excitatory transmitter release.

PMID- 1351790
TI  - A population-wide profile of prescription drug use in Saskatchewan, 1989.
AB  - OBJECTIVE: To measure the prevalence of prescription drug use in Saskatchewan in
      1989. DESIGN: Retrospective study. PARTICIPANTS: A total of 961,203 Saskatchewan
      residents (including those who died or were born during the study year) who were
      eligible for coverage under the Saskatchewan Prescription Drug Plan. The study
      population represented 94% of the province's total population; those excluded
      were mostly status Indians (for whom a federal plan is available). MAIN RESULTS:
      At least one prescription was received by 66.0% of the study population in 1989.
      The mean number of prescriptions per patient was 8.2, and the mean cost of drug
      material per prescription was $13.95. Females received substantially more
      prescriptions than males; the difference was particularly notable for
      cardiovascular agents, antidepressants and benzodiazepines. In the senior
      population 80.8% received at least one prescription; the mean number of
      prescriptions per patient was 18.4. The most commonly dispensed drug for the
      entire study population was amoxicillin (290 prescriptions per 1000 people);
      triazolam was the most frequently dispensed central nervous system drug (74
      prescriptions per 1000 people). Regional variation in overall drug use was
      remarkably small, although it increased at the drug-class level, especially for
      tranquillizers. The use of cardiovascular drugs was 27% to 32% higher (depending
      on how use was measured) per Regina resident than per Saskatoon resident.
      Benzodiazepines were commonly used on a long-term basis, despite recommendations
      to the contrary. CONCLUSIONS: The results quantify the prevalence of prescription
      drug use, underscore the importance of careful management of drug therapy by
      physicians and pharmacists (especially for seniors), illustrate substantial
      variation in drug therapy strategies and raise questions about utilization of
      benzodiazepines and cardiovascular drugs.

PMID- 1351791
TI  - Confusion, agitation and rigidity: early signs of NMS?

PMID- 1351793
TI  - XIII Congress of the European Society of Paediatric Neurosurgery. Berlin, 31 May
      2 June 1992. Abstracts.

PMID- 1351792
TI  - Reversal of vinblastine resistance by a new staurosporine derivative, NA-382, in
      P388/ADR cells.
AB  - Activities of a newly synthesized compound, N-ethoxycarbonyl-7-oxo-staurosporine
      (NA-382), on cyclic AMP-dependent protein kinase (A-kinase), Ca2+/phospholipid
      dependent protein kinase (C-kinase), and drug resistance were investigated and
      compared with those of staurosporine. Protein kinase-inhibitory activity of NA
      382 was lower but more selective to C-kinase than that of staurosporine. NA-382
      was less toxic to P388 cells and at a non-cytotoxic concentration completely
      reversed the vinblastine (VBL) resistance of Adriamycin-resistant P388 (P388/ADR)
      cells without influence on the effect of VBL on the parental P388/S cells.
      However, the cytotoxicity of staurosporine was too high to give the combination
      effect with VBL. NA-382 dose-dependently increased VBL-accumulation and inhibited
      VBL-efflux in P388/ADR with higher potency than staurosporine. Both compounds
      inhibited the photolabeling of [3H]azidopine on 140-kDa P-glycoprotein in the
      plasma membrane from the resistant cells. These results suggest that a
      staurosporine analog, NA-382, reverses multidrug resistance by inhibiting the
      drug-efflux system or P-glycoprotein.

PMID- 1351794
TI  - Attention-deficit hyperactivity disorder in adults.
AB  - It has been estimated that 30% to 70% of children who are diagnosed as having
      attention-deficit hyperactivity disorder (ADHD) will continue to show symptoms of
      the condition as adults. Since the prevalence of ADHD among school children may
      be 3% or more, its prevalence among adults may be 1% or 2%. The third revised
      edition of the Diagnostic and Statistical Manual (1987) of the American
      Psychiatric Association lists three essential features for the diagnosis of ADHD:
      "developmentally inappropriate inattention, impulsiveness, and hyperactivity."
      Other conditions associated with ADHD in adults include learning disabilities (or
      their sequelae), general anxiety disorder, drug and alcohol abuse, and dysthymic
      and cyclothymic disorders. Strong correlations have been found between ADHD and
      oppositional defiant and conduct disorders in children and an increased risk for
      antisocial disorders in adults. A combination of genetic, biologic, and
      environmental factors appears to be implicated in the etiology of ADHD. The
      management of adult ADHD requires a multimodal approach. The patient needs to be
      informed of the cause of his or her impulsive and often self-destructive
      behavior. Many patients will have learning difficulties that require evaluation
      and remediation by specialists in learning disabilities. Psychotherapy can help
      the patients resolve disturbances in perceptions of self and others and family
      therapy can address difficulties in the adult's relationships with family
      members. Pharmacotherapy of adult ADHD includes the use of central nervous system
      stimulants, such as methylphenidate, dextroamphetamine, and pemoline, of the
      tricyclic antidepressants imipramine and desimipramine, and of other
      antihypertensive, analgesic, and antimanic drugs.

PMID- 1351795
TI  - Effect of bunazosin, a selective alpha 1-adrenoceptor blocker, on ischemic
      myocardium in perfused rat heart.
AB  - The effects of bunazosin on the ischemic myocardium were investigated in
      isolated, perfused working rat hearts. Ischemia decreased the pressure-rate
      product and tissue adenosine triphosphate and creatine phosphate levels.
      Reperfusion did not restore the pressure-rate product nor the adenosine
      triphosphate levels completely. Bunazosin (5 x 10(-7) and 5 x 10(-6) mol/L)
      preserved the levels of adenosine triphosphate and creatine phosphate after 20
      minutes of ischemia and increased the extent of recovery of the pressure-rate
      product during reperfusion. The results suggest that bunazosin protects the
      myocardium against ischemic damage.

PMID- 1351796
TI  - Onset of action of loratadine and placebo and other efficacy variables in
      patients with seasonal allergic rhinitis.
AB  - In a double-blind study, 185 patients with seasonal allergic rhinitis were
      randomly assigned to receive 10 mg of loratadine or placebo once daily for three
      days. On day 1 of treatment, the onset of relief of symptoms within 30 minutes of
      drug administration was reported by 13% of the loratadine-treated patients and by
      4% of the placebo patients (P less than 0.05). At two hours after drug
      administration, 65% of the loratadine-treated patients and 48% of the placebo
      patients reported symptom relief. On day 3, the loratadine-treated patients
      reported a significantly greater relief of symptoms, and according to both
      physician and patient evaluations, the treatment response was significantly
      superior in the loratadine-treated than in the placebo patients. The incidence of
      sedation was 2% in the loratadine group and 1% in the placebo group.

PMID- 1351797
TI  - Effect of the elastase inhibitor eglin C in porcine endotoxin shock.
AB  - We wanted to demonstrate that the neutrophil elastase inhibitor eglin C reduces
      the loss of intravascular protein in endotoxin (LPS) shock and that effective
      concentrations are present in lymph. We used 45 anesthetized miniature pigs in a
      randomized, controlled trial. LPS 10 micrograms/kg/hr was given for 6 hr.
      Recombinant eglin C was given before LPS (250 nmol/kg) and continuously at 250
      nmol/kg/hr (n = 18); septic controls received saline (n = 18); nine nonseptic
      controls were used. Eglin C significantly reduced the loss of intravascular
      protein (plasma volume times plasma protein concentration) from -0.79 g/kg in
      septic controls to 0.42 g/kg in eglin C-treated animals and reduced plasma
      concentration of neutrophil elastase, bound to the leukocyte neutral protease
      inhibitor (LNPI), but systemic hypotension was unchanged. Six additional pigs
      were anesthetized, prepared with a thoracic lymph fistula, and received eglin C
      at 475 nmol/kg/hr; three received saline; three received LPS. Eglin C
      concentrations in lymph were comparable to those in plasma. We conclude that
      eglin C reduced the loss of intravascular protein during LPS shock and attained
      effective concentrations in lymph.

PMID- 1351798
TI  - The role of interleukin 2 (IL-2) and serum-soluble IL-2 receptor cells in
      idiopathic IgA nephropathy.
AB  - Interleukin 2 (IL-2) plays a central role in the immune response and may be
      involved in the derangement of cellular immunoregulation of idiopathic IgA
      nephropathy (IgAN). The aim of this study was to investigate the serum levels and
      production of IL-2 from peripheral blood mononuclear cells (PBMC) and the
      distribution of IL-2 receptor cells and serum-soluble IL-2 receptor cells (sIL
      2R) in patients with IgAN. Twenty-four patients with IgA nephropathy and 11
      healthy controls (age and sex matched) were studied during an infection-free
      period without signs of clinical activity at the moment of the study. Serum IL-2
      concentrations did not differ between patients and controls. The supernatant
      levels of IL-2 taken from 24-hr cultures of PBMC stimulated with
      phytohemagglutinin or tumor necrosis factor increased significantly in the
      patients but not in the controls. The percentage of IL-2R positive cells (CD25+)
      was increased in patients compared with controls. Moreover, IgAN patients had
      increased activated CD4+ lymphocytes when compared with the controls. Serum
      levels of sIL-2R were significantly higher in patients than in controls. There
      were no correlations among renal function, serum IgA levels, and urinary findings
      with cellular subsets or with IL-2 levels. However, sIL-2R was higher in the
      subgroup of patients with episodic macrohematuria and was closely related with
      the presence of red blood cells in the urinary sediment. We conclude that PBMC of
      IgA nephropathy patients have an overproduction of IL-2 after mitogenic
      stimulation, an increased helper T cell activity, increased IL-2R+ cells, and
      elevated serum levels of sIL-2R. These alterations are present in periods of
      apparent clinical inactivity. Finally, sIL-2R is closely related with hematuria,
      providing a good marker for disease activity. Our results suggest a pivotal role
      of IL-2 in cellular immune responses with regard to T cell activation in patients
      with IgAN.

PMID- 1351799
TI  - [Risks in dental practice. Premedication and sedation].

PMID- 1351800
TI  - 4th International Symposium on the Neuronal Ceroid Lipofuscinoses (Batten's
      Disease). Hamburg, June 11-13, 1992. Abstracts.

PMID- 1351801
TI  - [Loss of catecholaminergic neuron in the hypothalamus of multiple system
      atrophy].
AB  - Autonomic failure is one of the primary clinical features of multiple system
      atrophy (MSA); while the hypothalamus is thought to be a higher center regulating
      the autonomic nervous system. In the hypothalamus, catecholamine depletion had
      been confirmed by neurochemical studies but no marked changes had yet been
      demonstrated by pathological studies. Using three MSA and three control cases, we
      evaluated the quantitative changes of catecholamine (CA)-containing neurons in
      the hypothalamus. As markers of CA neurons, neuromelanin (NM)- and tyrosin
      hydroxylase (TH)-containing neurons were stained by Fontana-Masson and the
      immunohistochemical technique alternatively. Serial coronal sections, 10 microns
      thick, were evaluated every tenth section for NM neurons, while two sections were
      evaluated for TH neurons. The distributions of NM and TH neurons were almost
      identical; most of them were clustered in the periventricular and arcuate nuclei.
      The mean numbers of NM and TH neurons per slice were significantly lower in MSAs
      than in the controls (T test, p less than 0.01); the former were 21.0, 31.6, and
      13.7 in MSAs and 78.4, 54.1, and 84.3 in the controls, while the latter were 1.5,
      15.5, and 20.5 in MSAs and 48.0, 62.0, and 50.5 in the controls. The clinico
      pathological correlation was suggested by the significant differences in the
      number of TH neurons between two MSA cases: a case with severe orthostatic
      hypotension and a case with a milder one. The ratio of TH and NM neurons, as
      obtained from the adjusted sections, was constant in all MSA cases, and there was
      a positive statistical correlation, but it altered in each control case.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1351802
TI  - [Tyrosine hydroxylase-immunohistochemical study in the midbrain of experimental
      MPTP parkinsonism].
AB  - We have performed tyrosine hydroxylase (TH)-immunohistochemical study in the
      midbrain of experimental MPTP parkinsonism. Eight female adult crab-eating
      monkeys (macaca fascicularis) were subjected to the experiment and divided into
      four groups. In the acute experimental parkinsonism (group A), a daily dose of
      1.3 mg/kg MPTP was given intravenously for 7 days. Monkeys in the subacute group
      B were injected every other day a dose of 1.0 mg/kg MPTP intravenously for 7-14
      days. Chronic experimental parkinsonism group C was induced by administration of
      a dose of 0.5 mg/kg twice a week intravenously for 120 days. Group D served as a
      control. TH-immunoreactive cells were counted in substantia nigra pars compacta
      (SNc: consisting of lateral, intermediate, medial regions) and paramedian region
      of midbrain. The remaining TH-immunoreactive cells in group A,B and C were
      approximately 65.1%, 46.6% and 32.1% of the control group D. The ratio of TH
      immunoreactive cells in the lateral region of group A, B and C was lower than in
      group D. The TH-immunoreactive ratio in the intermediate and medial region of
      group B and C was lower than in group D. In the medial region of group C, the TH
      immunoreactive ratio was increased than in group B. In the paramedian region of
      all groups, there was no significant differences in the ratio of TH
      immunoreactive cells, but many more TH-immunoreactive nerve fibers were observed
      in group B and C than in group A and D. From the 90th day after MPTP treatment,
      monkeys in group C began to show a gradual recovery from the flexed posture and
      hypokinesia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351803
TI  - [An autopsy case of spinal subdural abscess in the aged--comparative study with
      neuroradiological findings].
AB  - An 82-year-old woman without previous medical problem noticed vague back pain on
      December 31, 1989, and was admitted to a hospital because she developed a fever,
      a rapidly progressive weakness followed by anesthesia of the lower extremities
      and sphincter disturbance. On myelography and myelo-CT, the spinal cord appeared
      to be displaced by an extramedullary mass which partially blocked the subdural
      space at the level of T-9 to L-1. When transferred to our hospital on January 8,
      1990, she was febrile and complaining of headache with meningeal signs.
      Percussion tenderness was present at T-8 to L-1 spinal spinous process.
      Neurological examination revealed that the patient had mild consciousness
      clouding, total paraplegia in the legs, sensory disturbance of a partial degree
      at L-1 to L-3 and totally below L-3, brisk but equal tendon reflexes in the upper
      extremities, areflexia in the legs with positive bilateral Babinski signs and
      sphincter disturbance. Otherwise she was neurologically unremarkable. Acute
      inflammatory reactions were prominent among the laboratory findings on admission.
      A lumbar tap yielded purulent fluid with more than 170,000 cells/mm3, 5,000 mg/dl
      of protein, 44 mg/dl of glucose and culture of the fluid isolated Escherichia
      coli. T1-weighted sagittal MRI disclosed an ill defined mass which showed the
      same or locally higher with gadopentetate dimeglumine (Gd-DTPA) signal intensity
      as soft tissue, compressing the spinal cord anteriorly from T-7 to L-3. The
      lesion was noticed to have a more extensive rostral-caudal extent than was
      inferred from myelography and myelo-CT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351805
TI  - Maturation of the goldfish (Carassius auratus) erythrocyte.
AB  - 1. Cohorts of [3H]thymidine-labelled erythrocytes were examined over a 42-day
      period in goldfish (Carassius auratus L.) recovering from phenylhydrazine HCl
      induced anemia under normoxic conditions at 20 +/- 1 degree C and maintained with
      minimal disturbance on a high nutritional plane. 2. As judged by changes in
      primary and derived hematological variables, maturation required 16-20 days. 3.
      Similar estimates were obtained using cytomorphic variables obtained by image
      analysing methods. 4. These suggest that juvenile red cells in this species can
      be identified on the basis of the following characteristics: major axis less than
      9.2 microM; one-sided surface area not greater than approximately 50 microns2;
      axis ratio greater than 0.774; form factor greater than 0.938. 5. Corresponding
      values for mature cells are: major axis greater than 11.2 microns; area greater
      than 68.5 microns2; axis ratio less than 0.716; form factor less than 0.912. 6.
      These criteria, with values for dividing and karyorrhectic cell numbers, offer a
      basis for more detailed and dynamic characterization of the erythron during
      response to environmental variation than has previously been possible.

PMID- 1351804
TI  - Analgesic oral efficacy of tramadol hydrochloride in postoperative pain.
AB  - Tramadol hydrochloride is a synthetic opiate agonist with a plasma elimination
      half-life of 5 to 6 hours and peak plasma levels at about 1 1/2 hours. It derives
      its activity from attachment to the mu-receptor and blockage of norepinephrine
      reuptake. The purpose of this single-dose, double-blind, placebo-controlled study
      was to determine the analgesic effectiveness of an oral administration of two
      dose levels of tramadol hydrochloride (75 or 150 mg) compared with the
      combination of 650 mg acetaminophen plus 100 mg propoxyphene napsylate in 161
      patients with severe postoperative pain after cesarean section. Analgesia was
      assessed over a 6-hour period. Treatments were compared on the basis of standard
      scales for pain intensity and relief and a number of derived variables based on
      these data. A global rating of the study medication was also used to compare
      treatments. The three active treatments were effective analgesics, statistically
      superior to placebo for many hourly and summary measures. A dose response was
      seen between the two tramadol doses, with the 150 mg dose providing significantly
      greater analgesia over the lower dose. The 75 mg dose of tramadol was generally
      more effective than the acetaminophen-propoxyphene combination after hour 2, and
      significantly so for some hourly time points, as well as for the global rating of
      the medication. The 150 mg dose of tramadol was significantly more effective than
      the acetaminophen-propoxyphene combination from hour 2 through hour 6 for the sum
      of pain intensity differences and total pain relief scores, as well as for the
      global rating of the medication. Tramadol hydrochloride at both dose levels is an
      effective analgesic agent and at 150 mg is statistically superior to the
      acetaminophen-propoxyphene combination. No serious adverse effects were observed;
      however, dizziness was more frequently reported with 150 mg tramadol.

PMID- 1351806
TI  - Localization and soma diameter of rat gluteus medius motoneurons.
AB  - 1. Retrograde transport of horseradish peroxidase was used to examine the
      localization and soma diameter of motoneurons innervating the deep (predominance
      of oxidative fibers) and superficial (predominance of non-oxidative fibers)
      portions of the gluteus medius muscle in rats. 2. The motoneurons innervating the
      deep portion were located caudally within the gluteus medius motoneuron pool and
      had smaller average soma diameter than that of motoneurons innervating the
      superficial portion. 3. These results suggest that the location of the muscle
      fibers within the muscle is related to the location of motoneurons within the
      motoneuron pool, and that the soma diameter of motoneuron innervating oxidative
      muscle fibers may be smaller than those innervating non-oxidative fibers in the
      rat.

PMID- 1351807
TI  - Taurine flux in chicken erythrocytes.
AB  - 1. The intracellular taurine concentration in chick erythrocytes increased with
      age. 2. Erythrocyte taurine influx and efflux rates increased with age. 3.
      Erythrocyte taurine influx decreased when the extracellular sodium concentration
      was below normal physiological concentrations. 4. Under hypo-osmotic conditions,
      taurine efflux from erythrocytes increased. 5. The data suggest that chick
      erythrocyte taurine metabolism changes during early post-hatch development and
      that one taurine function may be as an osmoregulator.

PMID- 1351808
TI  - Pituitary LH content and plasma LH levels following daily GnRH analogue treatment
      in male red-winged blackbirds (Agelaius phoeniceus).
AB  - 1. During the 14-day treatment period, plasma LH levels following GnRH analogue
      (GnRH-A) injections (10.0 micrograms) were significantly reduced after the 6th
      and the 14th injection. 2. One day post-treatment, the LH pituitary content was
      significantly reduced in GnRH-A-treated redwings compared to saline-injected
      controls. 3. Pituitary LH content was significantly higher in GnRH-A treated
      birds compared to control birds 14 and 28 days post-treatment and plasma LH
      levels were similar in both groups. 4. Hypersecretion of LH following GnRH-A
      injections appears to reduce pituitary LH content, acting as a stimulus for its
      synthesis. 5. These results suggest a higher LH synthesis and storage in the
      pituitary gland of the GnRH-A-treated birds compared to the control birds during
      the post-treatment period.

PMID- 1351809
TI  - Water proton ion in leg muscles of crayfish subjected to starvation.
AB  - 1. Using nuclear magnetic resonance, we studied the relationships of in vivo
      water to establish the correlation between the degree of starvation and the spin
      lattice or spin-spin relaxation times (T1 and T2, respectively) of water protons
      in the leg muscles of crayfish (Procambarus clarkii). 2. As the period of
      starvation increased, the water content as a component of body weight increased,
      and the T1 value was proportional to the increase in water content of the leg
      muscles of the crayfish. 3. The T2 value increased exponentially in comparison
      with the T1 value for each corresponding stage. 4. Our studies suggest that the
      state of the body water resulting from starvation was affected by cellular
      environmental change.

PMID- 1351810
TI  - Dietary vanadium and the oxidative state of hepatic and renal pyridine
      nucleotides.
AB  - 1. NAD, NADH, NADP and NADPH were measured in the livers and kidneys of chicks
      receiving 50 mg vanadium/kg diet. 2. There was no effect of dietary vanadium on
      the oxidative states of the nucleotides, although the growth rate was decreased.
      3. The lack of effect of vanadium on the oxidative status of the nucleotides was
      ascribed to the low tissue concentration of vanadium.

PMID- 1351811
TI  - Effect of clenbuterol on skeletal muscle atrophy in mice induced by the
      glucocorticoid dexamethasone.
AB  - 1. The ability of clenbuterol to antagonize the catabolic effect of the
      glucocorticoid dexamethasone on the skeletal muscles, soleus, gastrocnemius and
      extensor digitorum longus was studied in mice. 2. Daily injections of 5 mg
      dexamethasone/kg body weight over 10 days caused a significant (20%) loss of
      muscle weight and protein content in fast twitch but not in slow twitch muscles.
      3. Inclusion of clenbuterol (4 mg/kg) in the diet for the period of dexamethasone
      treatment partly prevented glucocorticoid-induced muscle atrophy, and increasing
      the concentration of clenbuterol to 8 mg/kg diet totally prevented glucocorticoid
      induced protein loss in all muscles.

PMID- 1351812
TI  - The effect of glycine administration on taurine concentration in the rat liver.
AB  - 1. The treatment of rats with glycine (2 mg/g) produced a marked decrease in the
      hepatic taurine content of neonate rats but not of adult rats. 2. The decrease
      observed in taurine concentration in the liver of newborn rats was not found in
      other organs, such as brain or kidney. 3. The results showed that the change in
      hepatic taurine concentration was dose- and time-dependent, suggesting the
      existence of an exchange mechanism between taurine and glycine in the rat liver
      that could participate in regulating the hepatic concentration of these amino
      acids.

PMID- 1351813
TI  - High affinity, Ca2+ specific ATPase and Na+K(+)-ATPase in the gills of a
      supralittoral crab Leptograpsus variegatus.
AB  - 1. The gills of Leptograpsus variegatus contain a high-affinity, Ca(2+)-activated
      ATPase, probably located in the basolateral plasma membrane of the gill
      epithelia. 2. The affinity of the ATPase for Ca2+ is in the micromolar
      concentration range (6-35 mumol/l). 3. The specific activity of the enzyme did
      not change during the moult cycle. The ATPase probably does not contribute
      substantially to increased calcium influx from the medium during the post moult
      period. 4. The enzyme is believed to function as a selective extrusion mechanism
      involved in the maintenance of a low cytosolic Ca2+ level in the epithelial
      cells.

PMID- 1351814
TI  - Fatty liver induced by the addition of excess cystine to a soy-bean protein diet
      in rats.
AB  - 1. The effects of excess cystine added to diets with casein, egg protein, soya
      bean protein and wheat gluten as protein source on liver and serum lipids of rats
      were compared. 2. The addition of excess cystine to a soya-bean protein diet
      produced lipid accumulation in the liver. 3. The addition of excess cystine to
      casein, egg protein and soya-bean protein diets, but not a wheat gluten diet,
      increased serum cholesterol.

PMID- 1351815
TI  - Blood chemistry of reindeer calves (Rangifer tarandus) during the winter season.
AB  - 1. Blood characteristics of reindeer calves fed on lichens were studied during
      the winter. 2. The serum total protein, albumin and globulin concentrations
      decreased during the winter, obviously partly due to protein deficiency in the
      diet. 3. High urea levels in autumn and midwinter were possibly reflections of
      increased stress and/or protein catabolism. 4. Marked lipolysis occurred in late
      winter, and thus increases were observed in fatty acids, glycerol, triglycerides
      and acetoacetate concentrations. 5. Serum sorbitol dehydrogenase (SDH) activity
      increased towards the spring, most probably reflecting changes in the liver. 6. A
      decrease in serum alkaline phosphatase (AP) activity occurred in midwinter due to
      cessation of growth. 7. It can be concluded that all the animals were at least in
      moderate condition throughout the winter and the physiological responses to a
      negative energy balanced reflected good adaptation.

PMID- 1351816
TI  - Long-term effects of dietary monounsaturated and polyunsaturated fatty acids on
      the lipid composition of erythrocyte membranes in dogs.
AB  - 1. Lipid analyses were conducted on erythrocyte membranes from dogs fed for 6
      months with a normal defatted diet supplemented with either olive or sunflower
      oil. 2. Levels of palmitic, stearic and arachidonic acids were only slightly
      affected by dietary fat. 3. The unsaturated fatty acids of n-9 series were
      elevated in all the phospholipid fractions analysed for olive oil-fed dogs while
      the n-6 fatty acids, with the exception of arachidonic acid, were elevated in
      sunflower oil-fed dogs. 4. In the olive oil group the 20:5 (n-3) acid was higher
      than in the sunflower oil group. 5. The unsaturation index and the
      cholesterol/phospholipid ratio increased along the time course in the sunflower
      oil group. Both increases are complementary in order to maintain the constant
      fluidity of membranes.

PMID- 1351817
TI  - Early-life patterns of plasma gut regulatory peptide levels in calves. Effects of
      age, weaning and feeding.
AB  - 1. The effects of age, weaning and feeding on the release of seven gut regulatory
      peptides [gastrin, cholecystokinin (CCK), secretin, vasoactive intestinal peptide
      (VIP), pancreatic polypeptide (PP), motilin and somatostatin] were studied in
      calves either exclusively milk-fed between birth and 91 days (P group) or weaned
      between 22-56 days of age (R group). 2. During the first 3 weeks, the basal
      plasma immunoreactive levels increased with age for secretin, CCK and PP,
      decreased for gastrin, motilin and somatostatin and were unaffected for VIP. The
      changes were particularly rapid for somatostatin and gastrin. After 3 weeks, no
      significant trend was observed with age in the P group. 3. Weaning resulted in an
      increase of basal gastrin, CCK, PP and VIP and in a decrease of basal secretin
      and somatostatin. 4. In the P group, the morning meal was followed 1 hr later by
      an increase of gastrin and CCK, and by a fall of secretin, PP, motilin and
      somatostatin, but no significant effect was observed in VIP. Weaning resulted in
      a reduction of the differences between the fasting and the post-feeding values.
      5. These changes suggest a large involvement of endocrine cells in the adaptation
      of gut tissues, secretions and motility at birth, during the maintenance at the
      pre-ruminant stage and at weaning.

PMID- 1351818
TI  - Dietary arginine requirement of young rainbow trout (Oncorhynchus mykiss).
AB  - 1. Two growth trials were conducted with young rainbow trout (Oncorhynchus
      mykiss) to determine the dietary arginine requirement under conditions of rapid
      weight gain at 15 degrees C. 2. The growth requirement does not exceed 4.2 g
      arginine/16 g dietary nitrogen and, thus, is much lower than the value of 6.0 g
      arginine/16 g dietary nitrogen presently listed by the NRC for Chinook salmon and
      widely applied to all Salmonids. 3. Comparison of the present results with the
      arginine requirement of the chick reveals remarkable similarity despite the
      phylogenetic distance between the two species, and demonstrates the need to re
      evaluate, as anomalously high, the presently-accepted value for Chinook salmon.

PMID- 1351819
TI  - Effects of a beta 2-adrenergic agonist, cimaterol and corticosterone on growth
      and carcass composition of male rats.
AB  - 1. Growth rate and carcass composition were measured in rats treated with
      cimaterol or vehicle only for 21 days, with corticosterone administered during
      the last 7 days of cimaterol or vehicle only treatment. 2. Cimaterol
      significantly stimulated the amount of protein in the carcass as well as
      gastrocnemius and plantaris muscles by 9-15%, and decreased carcass fat by 24%.
      3. Corticosterone treatment significantly decreased protein in the carcass and
      soleus, plantaris and gastrocnemius muscles by 13-33%. 4. The catabolic effects
      of corticosterone on carcass and muscle protein were reduced by pretreatment with
      cimaterol, suggesting that beta-adrenergic agonists may have some potential use
      in preventing muscle wasting during stressed states.

PMID- 1351820
TI  - Active and inactive renin in the plasma of the snake Bothrops jararaca.
AB  - 1. Complementing the work of Gervitz R. K., Hiraichi E., Fichman M. and Lavras A.
      A. C. Comp. Biochem. Physiol. 86A, 503-507 (1987), conditions have been
      established for measuring plasma renin activity (PRA) of the venomous snake
      Bothrops jararaca (Bj). 2. It corresponded to 115.9 +/- 11.5 ng equivalents of
      angiotensin II (AII) per ml of plasma (N = 13). 3. PRA did not increase when Bj
      plasma was submitted to acid-cryo-trypsin Bitis arietans venom activation of
      inactive renin. 4. This may indicate either absence of inactive renin in this
      plasma or lack of its activation, due to the already demonstrated (Nahas L.,
      Kamiguti A. S., Betti F., Martins I. S. S. and Rodrigues M. I., Comp. Biochem.
      Physiol. 69A, 739-743, 1981; Prezoto B. C., Hiraichi E., Abdalla F. M. F. and
      Picarelli Z. P., Comp. Biochem. Physiol. 99C, 135-139, 1991) absence of factor
      XII.

PMID- 1351822
TI  - Major buffering constituents in animal muscle.
AB  - 1. Among the muscles of six fish species, three mammals, and a bird, white muscle
      of skipjack tuna showed the highest buffering capacity (BC) in the pH range 6.5
      7.5, followed by the muscle of little-piked whale, chicken pectoralis minor, and
      mackerel white muscle. 2. Contribution of low-molecular weight components to the
      muscle BC was as high as 48-96%, while the contribution of muscle proteins was
      below 50%. 3. Histidine-related dipeptides and inorganic phosphate were found to
      be major buffering constituents in muscle. 4. The dipeptides accounted for the BC
      differences found between the species and muscle types.

PMID- 1351821
TI  - Redistribution of air within the lungs may potentiate "fright" bradycardia in
      submerged crocodiles (Crocodylus porosus).
AB  - 1. Voluntary undisturbed dives by Crocodylus porosus were short in duration (3.08
      +/- 1.87 min, mean +/- SD) and accompanied by a small but significant bradycardia
      (14.3 +/- 5.9% drop). 2. When crocodiles were disturbed underwater there was a
      rapid onset of "fright" bradycardia, to 65 +/- 6.0% of surface heart rates and
      dive durations were prolonged to 19.6 +/- 1.8 min. 3. The development of "fright"
      bradycardia was not accompanied by any increase in intratracheal pressure or
      expulsion of lung gas. However, sustained contraction of the abdomen and
      expansion of the thorax revealed a redistribution of air anteriorly within the
      lungs. 4. We propose that the redistribution of air within the lungs may generate
      an afferent signal which potentiates the initiation of a severe, dive-prolonging
      bradycardia.

PMID- 1351823
TI  - Mesotocin and oxytocin in the brain and plasma of an Australian marsupial, the
      northern brown bandicoot, Isoodon macrourus.
AB  - 1. Mesotocin (MT) and oxytocin (OT) were measured in the brain and plasma of
      bandicoots using reverse phase high performance liquid chromatography and
      specific radioimmunoassays. 2. MT and OT were found in the pituitary (1.25 +/-
      0.10 micrograms/MT; 0.725 +/- 0.077 micrograms/OT) and hypothalamus (38.37 +/-
      6.46 ng/MT; 19.1 +/- 4.61 ng/OT). Smaller amounts were present in the cerebral
      cortex. 3. Basal plasma concentrations ranged from 1.5 to 8.1 pg/ml for both
      peptides (N = 14) and were elevated by stress. 4. It was concluded that both MT
      and OT are secreted by the bandicoot brain and that stress stimulates secretion.

PMID- 1351824
TI  - Characterization of 2-[125I]iodomelatonin binding sites in the brain of a
      marsupial, Bennett's wallaby (Macropus rufogriseus rufogriseus).
AB  - 1. Specific high affinity binding of 2-[125I]iodomelatonin was detected in the
      brain of the pouch young of a marsupial, Bennett's wallaby. 2. Binding was rapid,
      stable, saturable and reversible. 3. Scatchard analysis indicated a single class
      of high affinity binding sites with an equilibrium dissociation constant (Kd) of
      68 +/- 13 pM, a maximal number of binding sites (Bmax) of 0.7 +/- 0.1 fmol/mg
      protein and a Hill coefficient (nH) of 1.12 +/- 0.10. 4. Specific binding was
      inhibited by GTP (1 mM) indicating that the melatonin receptor is coupled to a
      guanine nucleotide binding protein, and by melatonin and closely related
      analogues with a potency order identical to that reported previously in the brain
      of eutherian mammals, birds and a reptile. 5. These studies suggest that the
      melatonin receptor is well-conserved through evolution.

PMID- 1351825
TI  - In vivo and in vitro protein synthesis of oviducal pars recta by estradiol
      effect.
AB  - 1. Proteins secreted by toad oviductal pars recta are involved in fertilization
      and their biological activity is regulated by estrogens. 2. Effect of 17 beta
      estradiol on protein synthesis was examined on castrated animals by different in
      vivo and in vitro experimental approaches. 3. Different routes of L-[3H]leucine
      administration were assessed. An intralymphatic route was the most efficient for
      incorporating radioactivity per mg of trichloroacetic acid insoluble proteins. 4.
      Ligature of pars recta induces protein synthesis at a similar level to exogenous
      estradiol. 5. Electrophoretic pattern of radioactive proteins did not show
      synthesis of a specific protein related to the zone with biological activity. 6.
      Pars recta releases newly synthesized proteins in vivo into its fluid secretion
      as much as in vitro into culture medium.

PMID- 1351826
TI  - Haematology, red cell metabolism and blood chemistry of the black-faced cormorant
      Leucocarbo fuscescens.
AB  - 1. Haematology, red cell metabolism and blood chemistry of five fledgeling black
      faced cormorants Leucocarbo fuscescens were studied and the results were compared
      with previously reported data on several other sea-birds. 2. The mean erythrocyte
      count of the cormorant is similar to that of penguins but lower than that of
      flying, non-diving sea-birds. The cormorant's red cell mean cell volume (MCV) is
      lower than that of penguins but higher than that of non-diving sea-birds. 3.
      Leucocyte numbers are within expected limits for avian species. 4. Red cell
      enzymes: glucose phosphate isomerase, phosphofructokinase, aldolase and enolase
      are higher in the cormorant than in the little penguin; glyceraldehyde phosphate
      dehydrogenase, monophosphoglyceromutase, pyruvate kinase, lactate dehydrogenase
      and glutathione reductase are lower. 5. Haemoglobin electrophoresis showed a
      typical avian haemoglobin pattern.

PMID- 1351827
TI  - Coupling between the intracellular pH and the active transport of sodium in an
      epithelial cell line from Xenopus laevis.
AB  - 1. The relationship between the rate of active Na+ transport and intracellular pH
      (pHi, measured as the BCECF fluorescence) was studied in A6 monolayers in the
      presence of CO2. The total buffering power (beta total) and its components (beta
      i and beta CO2) were assessed at various pHi. 2. The activity of Na+/H+ and Cl
      /HCO3- exchangers were expressed in A6 cells; both antiports were found to
      participate in pHi homeostasis under standard conditions. 3. Alterations in the
      rate of Na+ transport induced variations in pHi. 4. Na+ transport rate was a
      hyperbolic function of external Na+ concentration. The curve was shifted by
      changing pHi: a mixed inhibition of Na+ transport by pHi was found. 5. The pHi
      appears as a possible mediator coupling the rate of Na+ transport across the
      apical and the basolateral membrane in tight epithelia.

PMID- 1351828
TI  - Accumulation of radiocalcium from the aquatic medium via the cloaca and bucco
      pharynx of Australian freshwater turtles (Chelidae).
AB  - 1. The cloacal and bucco-pharyngeal regions of three species of Australian
      freshwater turtles were experimentally compared for their ability to take up
      radiocalcium directly from the aquatic medium. 2. The cloacal route was at least
      4 times more important than the bucco-pharyngeal route for radiocalcium uptake,
      in each of the three species investigated. 3. Histological examination of
      anatomical regions in the cloaca showed that the cloacal bursae of three species
      (E. dentata, C. longicollis and E. signata) had abundant villi and infolded
      mucosal epithelia that increase the surface area of the epithelium exposed to the
      aquatic medium. 4. Electron microscopic studies on the mucosal epithelium of the
      cloacal bursae showed that it contained many structural characteristics
      indicative of an exchange function and consistent with the cloacal bursae being
      an important site of radiocalcium uptake within the cloaca.

PMID- 1351829
TI  - Changes in myosin and actin filaments in fast skeletal muscle after denervation
      and self-reinnervation.
AB  - 1. Myosin and actin filaments of the contractile apparatus of the denervated and
      self-reinnervated rat leg fast muscle were examined in ultrastructure. In
      parallel, the total contents of actin and of myosin heavy chains (MHC) were
      investigated. The results were compared with the corresponding ones in the slow
      muscle. 2. In the denervated-atrophying fast muscle the myosin filaments
      disappeared before the actin filaments. However, in contrast to the slow muscle,
      the local disproportion between the filaments was soon compensated, and their
      hexagonal arrangement was maintained for about one month after denervation. The
      contents of MHC and actin decreased, but their ratio remained similar to that in
      the controls. 3. In the later stage of atrophy the proportion of myosin to actin
      filaments and the ratio of the corresponding proteins decreased, and the
      hexagonal arrangement of filaments was disturbed. The denervated fast and slow
      muscles became similar (in the latter, such changes occurred during the initial
      weeks after denervation). 4. In the fast muscle recovering after reinnervation
      (on the third week after denervation) the numbers of myosin and actin filaments,
      and the contents of the corresponding proteins increased in parallel and the
      hexagonal arrangement of filaments was maintained (differently than those
      observed in the slow muscle).

PMID- 1351830
TI  - Regional differences for the D-amino acid oxidase-catalysed oxidation of D
      methionine in chicken small intestine.
AB  - 1. Enzymic oxidation of D-[1-14C]methionine (D-met) to 2-keto-4
      methylthiobutanoate (KMB) has been determined using 100,000 g supernatants
      prepared from chicken tissue homogenates. 2. The small intestinal mucosa contains
      substantial oxidative activity towards D-met, which represents about one-half and
      one-tenth the hepatic and renal activity, respectively. 3. KMB is poorly
      decarboxylated and rather transaminated to L-met. 4. The specific activity for D
      met oxidation in the duodenal mucosa is 1.5- and 4.0-fold than in the jejunal and
      ileal mucosa, respectively. 5. The intestinal D-met-oxidizing activity is
      dramatically altered by the D-amino acid oxidase specific inhibitor benzoate.

PMID- 1351831
TI  - Chromosome mapping of the human mitochondrial acetoacetyl-coenzyme A thiolase
      gene to 11q22.3----q23.1 by fluorescence in situ hybridization.

PMID- 1351832
TI  - Assignment of the chicken tyrosine hydroxylase gene to chromosome 6 by FISH.
AB  - The gene for tyrosine hydroxylase, the first and rate-limiting enzyme in the
      biosynthetic pathway of catecholamine neurotransmitters, has been localized in
      situ to chromosome 6 in the chicken. It is the first DNA marker to be reported
      for this telocentric macrochromosome. Use of a 45-kb biotinylated chicken
      specific cosmid probe and a sensitive fluorescent detection system proved to be
      highly efficient, with over 90% of metaphases showing positive hybridization
      signals on one or (usually) both chromosome 6 homologs, in physically mapping
      this single-gene locus.

PMID- 1351833
TI  - Report of the First International Workshop on Human Chromosome 2 mapping 1991.

PMID- 1351834
TI  - Report of the Second International Workshop on Human Chromosome 19 mapping 1992.

PMID- 1351835
TI  - Treatment of enterocutaneous and colocutaneous fistulas with early surgery or
      somatostatin analog.
AB  - Standard therapy of enterocutaneous (ECF) and colocutaneous (CCF) fistulas
      consists of "conservative" management, with surgery reserved for failures of
      maximal medical treatment. We conducted a five-year retrospective review of 28
      patients with low-output ECF and CCF to determine the outcome of early surgical
      and nonsurgical treatment of these conditions. Twelve men and 16 women with a
      mean age of 60 years presented with 22 ECF and 6 CCF. Six patients had early
      operative intervention in an attempt to close their fistulas, while the remaining
      22 patients were treated without surgery. In addition, four of the nonsurgical
      group received parenteral somatostatin analog (SA). None of the surgical patients
      was septic preoperatively (mean WBC = 9.7), the mean preoperative hospital stay
      was 11 days, and no patients required a proximal diverting stoma. All of the
      surgical group resumed normal gastrointestinal function within two weeks, and
      seven of the nine (78 percent) demonstrated no recurrence of the fistula at a
      mean follow-up of 8.3 months. Of the 22 medically treated patients, three of the
      four who received SA healed their fistulas within two weeks. Only two of the
      other 13 medically treated patients (15 percent) healed their fistulas. Early
      surgery or the use of SA should be considered in the treatment of patients with
      low-output intestinal fistulas.

PMID- 1351836
TI  - [Dental alloys and allergy. Case report].
AB  - The case of a 67-year-old woman, who had been wearing an upper partial removable
      denture with a cast metal framework made of CoCrMo alloy for years without any
      problems, is described. After the extraction of a molar tooth a nickel alloy
      retention was soldered to the framework. Following reinsertion allergic reactions
      appeared. The soldered joint showed considerable corrosion. After removing the
      retention and the soldered joint, the allergic reactions disappeared, although an
      epicutanceous test had revealed a positive reaction to cobalt. This case supports
      the high corrosion resistance and biocompatibility reported for CoCrMo alloys in
      the literature and the loss of these properties due to inadequate processing.
      Furthermore, the case illustrates a true allergic reaction. In contrast to the
      rather indiscriminate use of the term allergy to describe various vague
      disorders, this diagnosis should be restricted to clearly identified clinical
      situations.

PMID- 1351837
TI  - A trophoblast-specific factor(s) suppresses circulating prolactin levels and
      increases tyrosine hydroxylase activity in tuberoinfundibular dopaminergic
      neurons.
AB  - Rat choriocarcinoma (Rcho) cells, which are morphologically similar to
      trophoblast giant cells of the normal placenta and produce placental lactogen-I
      in vivo, were used to investigate placental feedback on PRL secretion and
      tuberoinfundibular dopaminergic neuronal activity. Rcho cells were injected into
      female rats either intracerebroventricularly 60-65 h before use or under the
      kidney capsule 10-14 days before use. The following endocrine conditions were
      used: 1) ovariectomized rats with or without bromocriptine treatment, 2) immature
      (40-44 days old) rats, 3) adult cycling (diestrous) rats, and 4) pregnant rats.
      Serum PRL levels in ovariectomized, diestrous, and immature female rats were
      suppressed to less than 20% of control levels by secretions from the Rcho cells.
      Tyrosine hydroxylase (TH) activity in the stalk-median eminence (SME) was
      increased 2-fold above control activity in Rcho-treated ovariectomized and
      immature female rats. When TH activity was reduced to 40% of control levels by 50
      h of bromocriptine treatment, secretions from Rcho cells increased TH activity
      3.5-fold to levels similar to those for Rcho alone. Even though Rcho treatment
      suppressed PRL levels, TH activity in the SME of cycling (diestrous) rats was not
      altered after either central (65 h) or peripheral (12 days) administration of
      cells. TH mRNA levels in the arcuate nuclei were unaltered by Rcho cells in
      immature female and adult cycling rats. TH mRNA levels in ovariectomized rats
      were markedly reduced 75% by 50 h of bromocriptine treatment and modestly reduced
      33% 65 h after injection of Rcho cells. However, Rcho cells partially reversed
      the bromocriptine-induced decline in TH mRNA to levels seen for Rcho cells alone.
      On day 7 of pregnancy, secretions from Rcho cells abolished the nocturnal and
      diurnal PRL surges characteristic of early pregnancy and suppressed circulating
      PRL levels throughout the day to less than 20% of intersurge PRL levels. Rcho
      cells eliminated the semicircadian rhythm in TH activity in the SME, which was
      out of phase with the twice daily PRL surges of early pregnancy. TH activity was
      increased by Rcho factor(s) at 0330 h (nocturnal surge) and 1800 h (diurnal
      surge), but not at 1000 h (intersurge). MMQ cells, pituitary-derived clonal PRL
      secreting cells, similarly terminated the biphasic rhythm of PRL release and
      tuberoinfundibular dopaminergic neuronal activity during early
      pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1351839
TI  - Immunocytochemical colocalization of hypothalamic progestin receptors and
      tyrosine hydroxylase in steroid-treated monkeys.
AB  - Progesterone (P)-induced PRL secretion in estradiol (E)-primed monkeys is not due
      to direct pituitary stimulation, because lactotropes do not express progestin
      receptors (PR). However, the hypothalamus, particularly the tuberoinfundibular
      dopaminergic system (TIDA), plays a major role in the regulation of PRL
      secretion. To determine whether hypothalamic dopamine neurons are progestin
      target cells, the colocalization of PR and tyrosine hydroxylase (TH), a
      phenotypic marker of dopaminergic neurons, was examined with double
      immunocytochemistry. Two methods for visualizing the antigens were applied; the
      first was a dual peroxidase method, and the second was a peroxidase-alkaline
      phosphatase method. In addition, the question of whether E induces PR in dopamine
      neurons was explored. Spayed female monkeys were treated with empty Silastic
      capsules, E-filled capsules for a period of 28 days, or E capsules supplemented
      with P capsules for the last 14 days of E treatment. Only the E- plus P-treated
      monkeys exhibited an increase in serum PRL during the P treatment period. Frontal
      sections at the level of the optic chiasm and arcuate nucleus were examined for
      the colocalization of TH and PR. After E treatment, hypothalamic PR-positive
      cells increased in both intensity and number. Neurons expressing both TH and PR
      were detected in the rostral hypothalamus, lateral to the third ventricle (A11
      rostral) and in a discrete subventricular population (A11-subvent). The lateral
      population continued caudally (A11-caudal). The A11-subvent population exhibited
      little steroid regulation. Of the remaining A11 TH neurons, approximately 20%
      exhibited PR in the spayed and E-treated groups. Addition of P doubled the
      percentage of PR-containing TH neurons in this group. Although very few TH
      positive neurons in the ventral arcuate nucleus contained PR (A12-ventral), many
      double labeled neurons were observed in the dorsal arcuate region (A12-dorsal).
      Ventral arcuate TIDA neurons were not regulated by steroids, but E plus P
      increased PR expression in A12-dorsal. Double labeled cells were rarely seen in
      the zona incerta (A13) or the emerging ventral tegmental area (A10). In summary,
      P probably does not act directly on ventral arcuate TIDA neurons to stimulate PRL
      secretion. However, the frequency of PR-positive dopamine neurons in the A11
      rostral, A11-caudal, and A12-dorsal groups increased with E and P treatment.
      Therefore, the contribution of the PR-positive periventricular dopamine neurons
      to progestin-stimulated PRL secretion may be important.

PMID- 1351840
TI  - ESWL: a method on retreat? II. ESWL or ISWL for difficult bile duct stones.

PMID- 1351838
TI  - Interaction of ethanol with signal transduction mechanisms mediating growth
      hormone release by rat pituitary cells in vitro.
AB  - The effects of ethanol on signal transduction mechanisms of rat GH (rGH) release
      were investigated in primary culture of rat anterior pituitary cells. Ethanol
      (30, 100, and 300 mM) had no significant effect on basal rGH release or cell
      content after a 4-h incubation or on intracellular cAMP levels at 30 min. Ethanol
      did not alter rGRH (10(-11) M)-stimulated rGH release, but at concentrations of
      100 and 300 mM it inhibited rGRH (10(-9) M)-stimulated rGH release by 12% (P less
      than 0.05) and 54% (P less than 0.01). In contrast, a dose-dependent stimulatory
      effect was observed on rGRH-induced cAMP accumulation. Ethanol enhanced the
      inhibitory effect of SRIH (10(-11) and 10(-9) M) on rGH release by up to 24% (P
      less than 0.01). Stimulation of rGH release by cAMP derivatives and forskolin was
      partially inhibited by ethanol, as was cAMP accumulation after forskolin
      treatment. Cholera toxin-stimulated rGH release was also inhibited by ethanol,
      whereas cAMP accumulation was increased. At the higher concentrations, ethanol
      enhanced rGH release after protein kinase-C activation by phorbol ester and after
      stimulation of calcium influx with Ca ionophore. No significant ethanol effect
      was noted on prostaglandin E2-stimulated rGH release, and ethanol did not alter
      rGH mRNA levels or proliferation of a pituitary somatomammotroph cell line. The
      results indicate that ethanol exerts multiple effects on systems mediating GH
      release from the pituitary in vitro. However, the inhibitory influence of ethanol
      on GH secretion is related primarily to the adenylate cyclase-cAMP pathway, which
      represents the major signal transducing system in the somatotroph.

PMID- 1351841
TI  - Basic study on the measuring of fatigue by the minimum audible pressure.
AB  - Nowadays, human senses of vision and hearing receive many stimulations. In
      particular, VDT work is commonly performed by people of all ages. Therefore, in
      order to regulate working hours we need to measure the fatigue due to VDT work.
      The current measuring system depends on the flicker value (CFF). This report
      describes a new measuring system which depends on the measurement of the
      fluctuation in the minimum audible pressure (MAP) while using the increase of
      threshold value as an index of fatigue, and the results of the related
      experiment. In Test 1, the test sound was set at the pure sound of 1,000 Hz. In
      Test 2, an ordinary hearing acuity inspection room was used, using the method of
      limit measurement and headphones (Telephonics, TDH39, MX41/AR). As a result, it
      was verified that the most suitable rate of increasing and decreasing audible
      pressure was by 2 dB or 1 dB. It was proved from these tests that the minimum
      audible pressure could be used satisfactorily as a practical index for absolute
      measurement of hearing sense fatigue.

PMID- 1351842
TI  - Single channel analysis of ketamine interaction with a quisqualate receptor.
AB  - The interactions of the general anaesthetic ketamine with the quisqualate
      sensitive L-glutamate receptor (QUIS-R) of locust muscle have been investigated
      at the single channel level using a M omega seal patch clamp technique. Low
      concentrations (10(-10) to 10(-9) M) of ketamine did not significantly alter the
      kinetics of the QUIS-R channel. Higher concentrations of ketamine decreased the
      probability of the channel being open, the frequency of channel opening and the
      channel mean open time, and increased the channel mean closed time. Probability
      density functions of channel dwell times indicate that during application of
      greater than 10(-8) M ketamine the distribution of channel openings becomes
      restricted mainly to brief events. These results are consistent with the view
      that ketamine blocks the open, and possibly also the closed, channel of locust
      muscle QUIS-R and that this anaesthetic dissociates only slowly from its blocking
      site(s).

PMID- 1351844
TI  - A comparison of the selectivities of SCH 23390 with BW737C89 for D1, D2 and 5-HT2
      binding sites both in vitro and in vivo.
AB  - The in vitro affinities (KIs) for SCH 23390 in D1, D2 and 5-HT2 binding assays
      were 0.4, 631 and 20 nM as compared with 0.3, 79 and 79 nM for BW737C89. The KB
      values, derived from their abilities to right-shift dopamine-mediated dose
      dependent increases in striatal adenylyl cyclase activity, were 0.8 and 0.5 nM
      for SCH 23390 and BW737C89, respectively. Thus, BW737C89 was a highly potent
      dopamine D1 receptor antagonist and, although it was less D1/D2-selective than
      SCH 23390, it was more D1/5-HT2-selective. Both SCH 23390 and BW737C89 (0.1-100
      mumol/kg s.c.) exhibited a selective dose-dependent protection of D1, but not D2,
      binding, from inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline
      (EEDQ, 8 mg/kg s.c.) as measured by [3H]SCH 23390 (D1) and [3H]spiperone (D2)
      binding. The ED50 values for this selective protection of D1 binding were similar
      and were between 1 and 3 mumol/kg s.c. BW737C89 showed no protective effect at
      all on the inactivation of [3H]ketanserin (5-HT2) binding by EEDQ whereas SCH
      23390 started to show protection at doses of 10 mumol/kg s.c. and above. A direct
      comparison of the time course of the effects of pretreatment of a dose of 30
      mumol/kg s.c. of both compounds to protect 5-HT2 binding was carried out. This
      study confirmed the complete lack of protective effect of BW737C89 from 1 to 4 h
      of pretreatment whereas SCH 23390 exhibited 62, 29 and 28% protection at 1, 2 and
      4 h pretreatment respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351843
TI  - The putative polyamine antagonists ifenprodil and SL 82.0715 enhance dopamine
      efflux from rat striatal slices independent of NMDA receptor activation.
AB  - NMDA stimulated the release of endogenous or tritiated dopamine from rat striatal
      slices and tritiated norepinephrine from cortical and hippocampal slices. The
      putative polyamine antagonists ifenprodil and SL 82.0715 inhibited
      [3H]norepinephrine release from cortical and hippocampal slices but enhanced the
      basal efflux of endogenous and tritiated dopamine from striatal slices.
      Incubation of striatal slices in a calcium-free buffer did not ameliorate these
      effects suggesting that the increase in dopamine efflux was not due to a calcium
      dependent release process. Superfusion of striatal slices with 10 microM of
      either ifenprodil, cocaine, or amphetamine resulted in a significant release of
      tritiated dopamine which was reversed when the slices were again superfused with
      non-drug-containing buffer. The release observed in the presence of 10 microM
      ifenprodil (7-fold increase over basal) was intermediate between that observed
      for cocaine (3-fold increase) and amphetamine (12-fold increase). Both ifenprodil
      and SL 82.0715 also blocked the uptake of [3H]dopamine into striatal synaptosomes
      with IC50 values of approximately 1.5 microM. This was again intermediate between
      the values obtained for cocaine (0.43 microM) and amphetamine (4.2 microM). These
      results suggest that ifenprodil and its analog SL 82.0715 may act as indirect
      dopamine agonists by both blocking presynaptic dopamine uptake and by directly
      increasing the basal efflux of dopamine.

PMID- 1351845
TI  - The effect of hypercholesterolaemia and atherosclerosis on alpha-adrenoceptor
      mediated vasoconstriction in conscious rabbits and rabbit aorta.
AB  - Rabbits were fed a diet containing 1% cholesterol for 4 or 8 weeks and the
      constrictor responses to alpha-adrenoceptor agonists, as well as endothelium
      dependent and endothelium-independent dilatation, were examined both in vivo and
      in vitro. The high cholesterol diet caused a significant elevation of plasma
      cholesterol concentration but no macroscopic evidence of atherosclerosis after 4
      weeks whereas after 8 weeks there was a significant development of
      atherosclerotic lesions in the thoracic and abdominal aorta. In conscious rabbits
      pressor responses to the non-selective alpha-adrenoceptor agonist noradrenaline
      and the selective alpha 1-adrenoceptor agonist phenylephrine were enhanced after
      4 weeks but returned to control levels after 8 weeks on the diet. The pressor
      responses to the alpha 2-adrenoceptor agonist B-HT 920 were reduced by the
      development of atherosclerosis. In the isolated thoracic aorta from these rabbits
      contractile responses to noradrenaline were impaired by hypercholesterolaemia
      whereas responses to phenylephrine were unaffected. Endothelium-dependent
      relaxation was impaired by hypercholesterolaemia both in vivo and in vitro after
      4 and 8 weeks on the diet whereas endothelium-independent relaxation was not
      affected. These results indicate that the effect of hypercholesterolaemia on
      alpha-adrenoceptor-mediated constriction is dependent on: (1) the absence or
      presence of atherosclerotic lesions, (2) the size of the artery and (3) the
      subtype of alpha-adrenoceptor involved in the response. There does not appear to
      be any relationship between the loss of endothelium-dependent relaxation in
      hypercholesterolaemia and the observed changes in adrenergic vasoconstriction.

PMID- 1351846
TI  - Autoradiographic localization of [3H]quinpirole binding to dopamine D2 and D3
      receptors in rat brain.
AB  - A radiolabelled form of the dopamine agonist, quinpirole (LY17155), has been
      evaluated as a ligand for dopamine receptors in the rat brain. Quinpirole has
      been reported to be a selective D2 dopamine agonist; however, a recent report has
      indicated that it may have high affinity for a novel dopamine binding site which
      has been termed D3. In rat brain sections, [3H]quinpirole binding exhibited a
      distribution similar to that described for dopamine D2 receptors using either
      agonist or antagonist labelling. High densities of binding could be found in
      caudate-putamen, nucleus accumbens, olfactory tubercle and islands of Calleja.
      When the labelling was done in the presence of 10 microM guanylyl-5'
      imidodiphosphate to convert the dopamine D2 receptor to a 'low affinity agonist
      conformation', binding was inhibited in most brain regions with the notable
      exception of the islands of Calleja which retained most of the [3H]quinpirole
      binding. The guanine nucleotide insensitivity of this binding and distribution of
      this site indicates that [3H]quinpirole is binding to dopamine D3 receptors in
      this region of the brain. Therefore, these results indicate that [3H]quinpirole
      labels a high affinity agonist conformation of dopamine D2 receptors as well as
      dopamine D3 receptors in rat brain. In addition, this study provides the first
      detection the dopamine D3 receptor protein in the brain.

PMID- 1351847
TI  - Effects of presynaptic alpha-adrenoceptors and neuronal reuptake on noradrenaline
      overflow and cardiac response.
AB  - Using an in situ perfused, innervated rat heart model, we studied the effects of
      presynaptic alpha-adrenergic and neuronal reuptake inhibition on evoked
      noradrenaline (NA) overflow and the postsynaptic response by sympathetic ganglion
      stimulation. NA overflow was significantly increased by neuronal reuptake
      inhibitors (desipramine and (+)-oxaprotiline) or by alpha-adrenoceptor
      antagonists (phentolamine and yohimbine), but the inotropic response was
      augmented only by alpha-antagonists. In the presence of desipramine, nerve
      stimulation induced a frequency-dependent increase in NA overflow and
      postsynaptic response, both were enhanced by yohimbine. In the absence of
      desipramine, however, postsynaptic response was potentiated by yohimbine despite
      an unchanged (at 2 and 5 Hz) or even reduced NA overflow (at 10 Hz). Thus, this
      study suggests that NA release and cardiac response are modulated by presynaptic
      alpha-adrenoceptors, and that the neuronal reuptake modifies the amount of NA
      overflow but has little effect on the postsynaptic response.

PMID- 1351848
TI  - Cardiovascular effects of microinjections of quipazine into nuclei of the medulla
      oblongata in anaesthetized cats: comparison with L-glutamate.
AB  - Unilateral microinjections of quipazine (0.9 micrograms in 50 nl) into the
      subretrofacial nucleus produced hypertension and a slight tachycardia associated
      with an increase in renal sympathetic nerve activity. Microinjections of
      quipazine lateral, caudal or rostral to this nucleus failed to alter blood
      pressure and heart rate. Similarly, microinjections of l-glutamate (3 nmol in 15
      nl) into the subretrofacial nucleus elicited hypertension, tachycardia and renal
      sympatho-excitation. The magnitude of the pressor response to quipazine was
      smaller than the response elicited by l-glutamate but its duration was longer.
      Microinjections of quipazine into the lateral tegmental field at l-glutamate
      hypertensive sites failed to alter arterial blood pressure and heart rate. In
      contrast, microinjections of quipazine into the caudal ventrolateral medulla or
      into the nucleus tractus solitarii produced hypotension and sympatho-inhibition.
      These effects were prevented by microinjections of the 5-HT2 receptor
      antagonists, LY 53857 or BW 501C. The present results indicate that stimulation
      of 5-HT2 receptors of the subretrofacial nucleus produces hypertension and
      sympatho-excitation whereas stimulation of 5-HT2 receptors in the caudal
      ventrolateral medulla and in the nucleus tractus solitarii produces hypotension
      and sympatho-inhibition.

PMID- 1351849
TI  - Investigations of prejunctional alpha 2-adrenoceptors in rat atrium, vas deferens
      and submandibular gland.
AB  - We have examined the effects of a series of alpha 2-adrenoceptor antagonists on
      the stimulation-evoked release of tritium from rat atrium, vas deferens and
      submandibular gland pre-incubated with [3H]noradrenaline, and correlated these
      potencies with affinities for the alpha 2A-ligand binding site of human platelet
      and the alpha 2B-ligand binding site of rat kidney. The alpha 2B-selective
      adrenoceptor antagonists prazosin and ARC 239 showed significantly higher, and
      the alpha 2A-selective antagonist BRL 44408 showed significantly lower, potency
      in atrium than in vas deferens and submandibular gland. Yohimbine and BDF 8933
      failed to distinguish between prejunctional alpha 2-adrenoceptors or between
      ligand binding sites. It is concluded that the prejunctional alpha 2-adrenoceptor
      of rat atrium resembles the alpha 2B-ligand binding site, and differs from the
      prejunctional alpha 2-adrenoceptors of rat vas deferens and submandibular gland,
      which resemble the alpha 2A-ligand binding site.

PMID- 1351850
TI  - Effect of alpha 1-adrenoceptor blockade on the development of hypertension in the
      spontaneously hypertensive rat.
AB  - There is a large body of evidence to suggest that the sympathetic nervous system
      plays a critical role in the development of hypertension and vascular medial
      hypertrophy in the spontaneously hypertensive rat (SHR). The synthesis of a water
      soluble, specific alpha 1-adrenoceptor antagonist (terazosin) has permitted an
      examination of the influence of alpha 1-adrenoceptors on those two phenomena.
      Thus, in the present study, terazosin (43 mg/kg per day) was administered to SHR
      and Wistar-Kyoto (WKY) rats from 4.5 to 12 weeks of age, and a number of
      assessments made in vitro and in vivo. In the SHR, the development of
      hypertension was not prevented by terazosin. The drug did not influence blood
      pressure in the WKY. This was despite the fact that animals which had been
      chronically treated with terazosin displayed marked alpha-adrenoceptor blockade
      in vivo. The response of systolic blood pressure to tyramine and noradrenaline
      was significantly reduced in animals which had been chronically treated with
      terazosin. In both the SHR and WKY, chronic administration of terazosin did not
      influence vascular concentrations of 3-methylhistidine, a biochemical marker for
      contractile proteins and vascular medial hypertrophy. The results therefore argue
      against a role of alpha 1-adrenoceptors in the development of hypertension and
      vascular medial hypertrophy in the SHR.

PMID- 1351851
TI  - Rapid fibroblast growth factor-induced increases in protein phosphorylation and
      ornithine decarboxylase activity: regulation by heparin and comparison to nerve
      growth factor-induced increases.
AB  - Fibroblast growth factors (FGFs), like nerve growth factor (NGF), induce
      morphological differentiation of PC12 cells. This activity of FGF is regulated by
      glycosaminoglycans. To further understand the mechanisms of FGF and
      glycosaminoglycan actions in PC12 cells, we studied the regulation of protein
      phosphorylation and ornithine decarboxylase (ODC) activity by FGF in the presence
      and absence of heparin. As with NGF, aFGF and bFGF increased the incorporation of
      radioactive phosphate into the protein tyrosine hydroxylase (TH). The increase in
      TH phosphorylation was localized to the tryptic peptide, T3. Both T3 and T1
      phosphorylations occur in response to NGF, but there was no evidence that aFGF or
      bFGF stimulated the phosphorylation of the T1 peptide. This result suggests
      differential regulation of second messenger systems by NGF and FGF in PC12 cells.
      Heparin, at a concentration that potentiated aFGF-induced neurite outgrowth 100
      fold (100 micrograms/ml), did not alter the ability of aFGF to increase S6
      phosphorylation or ODC activity. One milligram per milliliter of heparin, a
      concentration that inhibited bFGF-induced neurite outgrowth, also inhibited bFGF
      induced increases in S6 phosphorylation and ODC activity. These observations
      suggest (i) that acidic and basic FGF activate a protein kinase, possibly protein
      kinase C, resulting in the phosphorylation of peptide T3 of TH; (ii) that the
      FGFs and NGF share some but not all second messenger systems; (iii) that heparin
      potentiates aFGF actions and inhibits bFGF actions in PC12 cells via distinct
      mechanisms; (iv) that heparin does not potentiate the neurite outgrowth promoting
      activity of aFGF by enhancing binding to its PC12 cell surface receptor; and (v)
      that heparin may coordinately regulate several activities of bFGF (induction of
      protein phosphorylation, ODC and neurite outgrowth) via a common mechanism, most
      likely by inhibiting the productive binding of bFGF to its PC12 cell surface
      receptor.

PMID- 1351852
TI  - Alveolar macrophage populations are distorted in immunocompromised patients with
      pneumonitis.
AB  - Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from
      patients presenting with pneumonitis: 30 human immunodeficiency virus (HIV)
      infected individuals and 12 transplant recipients. Nine normal volunteers acted
      as controls. The cells were washed and cytospins prepared. Monoclonal antibodies
      (MoAbs) and immunoperoxidase methods were used to analyse the expression of HLA
      DR molecules as well as phenotypic macrophage markers. P values apply to the
      differences between medians using the Mann-Whitney test. Median percentages of
      macrophages, lymphocytes and neutrophils were similar in all three groups. No
      differences were found in the median percentages of macrophages expressing the
      monocyte phenotype (MoAb UCHM1, CD14). However, in HIV-infected patients and
      transplant recipients a median of only 45% of macrophages expressed the pan
      macrophage phenotype identified by MoAb EBM11 (CD68) in contrast with 98% in the
      normal volunteers. The AM population expressing the dendritic cell marker (MoAb
      RFD1) was also markedly reduced in both groups of immunocompromised patients (2
      vs 28% in normal volunteers). Transplant recipients had significantly more
      phagocytic cells identified by MoAb RFD7 than the HIV-infected patients (25 vs
      2%), but the numbers were still low when compared with the volunteers (48%). HLA
      DR expression on BAL cells was reduced by 90% in both immunocompromised groups.
      For the transplant recipients, severity of pneumonitis was correlated with
      expression of dendritic cell marker RFD1, (Spearman's rank correlation r = 0.538,
      p less than 0.05) and pan-macrophage marker EBM11 (r = 0.581, p less than 0.05),
      while no such correlation was found in HIV-infected patients. These results
      suggest that a defective macrophage population is probably a serious factor
      contributing to immunosuppression.

PMID- 1351853
TI  - Secretory leucocyte proteinase inhibitor: inhibition of fibronectin degradation
      by neutrophil elastase.
AB  - Degradation of surface-bound fibronectin of the upper respiratory tract by human
      leucocyte elastase (HLE) was shown to favour colonization of these mucosal
      surfaces by Gram-negative bacteria. We investigated the degradation of
      fibronectin by purified HLE and by enzymes released from stimulated human
      polymorphonuclear leucocytes (PMNs), in the presence of recombinant secretory
      leucocyte proteinase inhibitor (rSLPI) and alpha 1-proteinase inhibitor (alpha 1
      PI), the two main inhibitors of HLE within the airways. Our results show that HLE
      degraded fibronectin at concentrations as low as 0.2 nM. To inhibit the
      degradation of fibronectin by pure HLE in an experimental system in which the
      enzyme was premixed with inhibitor, a twofold molar excess of rSLPI and an
      equimolar concentration of alpha 1-PI were required. On the other hand, a
      fivefold molar excess of rSLPI was necessary to inhibit degradation of
      fibronectin by enzymes released from stimulated neutrophils. In order to estimate
      the role of oxidants generated by stimulated PMNs in the activation of the
      inhibitory capacity of rSLPI by stimulated PMNs, we preincubated PMNs with
      antioxidants such as superoxide dismutase, methionine, catalase or Na-azide prior
      to stimulation of the cells. Under these conditions, a threefold molar excess of
      rSLPI over released HLE was required to inhibit the degradation of fibronectin,
      raising the possibility that either exogenous or endogenous antioxidants in the
      lung could be important in improving the efficacy of this therapeutic
      antiprotease. We conclude that a molar excess of rSLPI to HLE is always necessary
      to inhibit fibronectin degradation by HLE, and that addition of antioxidants
      partly prevents the inactivation of rSLPI by oxidants released from stimulated
      PMNs.

PMID- 1351854
TI  - No independent association between HSP70 gene polymorphism and IDDM.
AB  - A role for heat shock proteins (HSPs) in autoimmunity has recently been suggested
      by several authors. Autoantibodies against HSPs have been associated with such
      autoimmune diseases as systemic lupus erythematosus, polymyositis, and the NOD
      mouse model of diabetes. Moreover, genes for the major 70,000-M(r) HSP (HSP70)
      are located within the MHC. To investigate a potential association of an HSP70-2
      gene polymorphism with insulin-dependent diabetes mellitus (IDDM), we analyzed
      restriction-fragment-length polymorphism (RFLP) of this gene in 29 families with
      one or more member affected by IDDM. With the enzyme PstI, as reported
      previously, two HSP70-2 alleles of 8.5- and 9.0-kb were found. The 8.5-kb allele
      was found more frequently on diabetic haplotypes compared with control haplotypes
      (41 of 66 [62%] vs. 20 of 46 [43%], P = 0.03). This association was due to the
      conservation of alleles on extended haplotypes we previously reported to be
      associated with diabetes on initial analysis of families. Twenty-three of 26
      diabetic DR3 haplotypes and 3 of 3 normal DR3 haplotypes and all instances of
      [HLA-B8, SC01, DR3] and [HLA-B18, F1C30, DR3] had the 8.5-kb allele, whereas 0 of
      9 normal DR2 haplotypes and 0 of 2 diabetic DR2 haplotypes had the 8.5-kb allele
      (P = 8 x 10(-7) DR3 vs. DR2 haplotypes). The alleles were equally distributed
      among DR4 haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351855
TI  - [International scientific conference "Ecology of high-altitude regions" (August
      26-31, 1991, Bishkek)].

PMID- 1351856
TI  - [All-Union symposium IV "Stress, adaptation and dysfunctions" (June 27-28, 1991,
      Kishinev)].

PMID- 1351857
TI  - Proliferating cell nuclear antigen expression in normal, preneoplastic, and
      neoplastic colonic epithelium of the rat.
AB  - Expression of the proliferating cell nuclear antigen (PCNA) was examined in
      normal rat intestinal tissues and in carcinogen-treated nonneoplastic and
      neoplastic colonic mucosa. In the normal intestine, PCNA expression was confined
      to the expected region of the proliferative compartment. A strong correlation was
      observed between PCNA labeling index and both [3H]thymidine labeling index (R =
      0.993, P = 0.007) and percent of cells in S phase as determined by flow cytometry
      (R = 0.982, P = 0.018) and between the location of the maximal staining for PCNA
      and [3H]thymidine (R = 0.997, P less than 0.05). In animals treated with
      dimethylhydrazine (DMH), crypt hyperplasia, an increased PCNA labeling index, and
      shifts in both the region of maximal and the upper extent of PCNA expression were
      observed during DMH exposure; significant crypt hyperplasia and expansion of the
      PCNA-positive compartment persisted after completion of DMH injections. The
      patterns of PCNA expression and bromodeoxyuridine incorporation were similar in
      DMH-induced tumors. It is concluded that PCNA immunohistochemistry can be used as
      a reliable marker of the proliferative compartment in both normal and neoplastic
      colonic mucosa.

PMID- 1351858
TI  - Evidence for hormonal inhibition of exocrine pancreatic function by somatostatin
      28 in humans.
AB  - Somatostatin 28 (S-28), originating in gastrointestinal cells, is secreted into
      the circulation and increases in humans after ingestion of a mixed meal. To
      evaluate the possibility that the increased levels of S-28 post cibum might
      modulate the release of enzymes and bicarbonate from the exocrine pancreas, S-28
      was infused intravenously into healthy volunteers to levels seen after food
      intake. During S-28 infusion, the output of lipase, trypsin, amylase, and
      bicarbonate stimulated by either exogenous cholecystokinin octapeptide or
      endogenous signals from intraduodenal administration of tryptophan or a mixture
      of amino acids was significantly reduced. It is concluded that S-28 released from
      the gut during food intake modulates pancreatic exocrine function in humans.

PMID- 1351859
TI  - Increased total vascular capacity in conscious cirrhotic rats.
AB  - The purpose of the present study was to determine the role of the systemic venous
      circulation in the hemodynamic alterations of the cirrhotic disease. Cardiac
      output (thermodilution; n = 8), mean circulatory filling pressure (balloon
      technique; n = 6), and blood volume (Evans blue dye; n = 7) were investigated in
      a rat model of liver cirrhosis without ascites induced by a 12-week
      individualized CCl4/phenobarbital treatment. Compared with control rats,
      conscious cirrhotic rats showed a hyperdynamic circulation characterized by
      normotension, high cardiac output (51 +/- 4.8 vs. 28.6 +/- 1.3 mL.min-1.100 g-1;
      P less than 0.01), and expanded blood volume (6.5 +/- 0.15 vs. 5.4 +/- 0.22
      mL.100 g-1; P less than 0.05). There were no significant differences between
      control and cirrhotic rats in mean circulatory filling pressure (6.40 +/- 0.27
      vs. 5.99 +/- 0.22 mm Hg, respectively) or in the pressure gradient for venous
      return (6.17 +/- 0.19 vs. 5.8 +/- 0.21 mm Hg, respectively). To further examine
      the venous tone, effective vascular compliance was estimated with the vascular
      filling-blood volume relationship by measuring the vascular filling before and
      after rapid changes in volume (+/- 8 mL.kg-1). Compliance was similar in both
      control and cirrhotic rats (3.15 +/- 0.26 and 3.41 +/- 0.21 mL.mm Hg-1), but the
      vascular filling-total blood volume relationship of the cirrhotic rats was
      displaced toward the volume axis. In conclusion, the increase in blood volume
      without changes in mean circulatory filling pressure (or venous tone) of the
      cirrhotic rats indicates a situation with venodilation and elevated total venous
      capacity; this is likely to be an important mechanism that could explain the
      hyperdynamic circulation of the cirrhotic disease.

PMID- 1351860
TI  - International Symposium on Biology of Actinomycetes. Madison, Wisconsin, 11-16
      August 1991.

PMID- 1351861
TI  - Proliferating cell nuclear antigen in oesophageal diseases; correlation with
      transforming growth factor alpha expression.
AB  - This study was designed to correlate mucosal proliferation in Barrett's
      oesophagus with expression of a growth promoting peptide, transforming growth
      factor alpha (TGF alpha). Oesophageal mucosa was studied from 50 patients with
      oesophageal disease who had been treated by oesophagectomy. Histological analysis
      showed a range of oesophageal pathology - 18 patients had gastric type Barrett's
      mucosa, 18 had intestinal type Barrett's mucosa, and 14 had oesophageal
      adenocarcinomas. Sections were stained immunohistochemically for proliferating
      cell nuclear antigen (PCNA) (an index of cellular proliferation) and TGF alpha.
      PCNA immunostaining was seen mainly in the basal cells of the neck/foveolar
      epithelial compartment of the glands in Barrett's oesophagus. However, in mucosa
      with high grade dysplasia, the proliferative compartment extended upwards into
      the superficial layers of the glands. At least 2000 cells were counted in each
      patient to determine the proportion with PCNA immunoreactivity (PCNA labelling
      index). The labelling index was highest in adenocarcinoma (25%) and in Barrett's
      intestinal type mucosa with high grade dysplasia (26%) compared with intestinal
      type mucosa with no significant dysplasia (20%) and Barrett's gastric type mucosa
      (12%). There was a significant positive correlation between PCNA labelling
      indices and TGF alpha expression in Barrett's mucosa (p less than 0.01). In
      glands showing high grade dysplasia, TGF alpha immunoreactivity was seen in the
      same regions of the glands as PCNA immunoreactivity, indicating the possibility
      of involvement of TGF alpha in (pre) neoplastic proliferation in Barrett's
      oesophagus.

PMID- 1351862
TI  - Ha-ras polymorphisms in epithelial ovarian cancer.
AB  - Unusual restriction fragment length polymorphisms (RFLPs) of the Ha-ras locus
      have been found in DNA from leukocytes and tumor tissue of cancer patients. To
      determine whether rare alleles would be observed frequently in patients with
      ovarian cancer, Ha-ras RFLPs were studied in DNA from 42 different ovarian
      epithelial tumors and from the peripheral blood leukocytes of 76 normal
      individuals. Four common, seven intermediate, and seven rare alleles were
      detected overall. Similar fractions of rare alleles were found in DNA from
      ovarian cancers and from the peripheral blood of normal individuals. Thus, the
      frequency of unusual Ha-ras RFLPs did not distinguish patients with ovarian
      cancers from apparently healthy individuals.

PMID- 1351863
TI  - Gastric carcinoma cells with endocrine differentiation show no evidence of
      proliferation.
AB  - The proliferative activity of gastric cancer cells with endocrine features was
      evaluated in five cases by means of a double-immunostaining procedure. The
      endocrine cells were recognized by a monoclonal antibody to chromogranin A (CGA)
      and the proliferative activity by a monoclonal antibody to proliferating cell
      nuclear antigen (PCNA). With the use of two different chromogens it was easy to
      determine whether CGA was located in the cytoplasm and whether PCNA was located
      in the nucleus of the same section. The CGA-positive endocrine cells of the
      normal gastric antral mucosa could be readily distinguished from the PCNA
      positive cells scattered in the mucosal neck zones. Over 1,000 CGA-positive
      cancer cells were counted per case. A few cells (average, less than 1.0%)
      exhibited faint nuclear staining with anti-PCNA; in no instance was unequivocal
      PCNA reactivity demonstrable in the gastric cancer cells with endocrine
      differentiation. By contrast, the PCNA reaction was positive in one fourth to one
      third of the other cancer cells. These observations suggest that gastric cancer
      cells with endocrine features are differentiated and do not participate in the
      cell cycle.

PMID- 1351864
TI  - Fibrohistiocytic differentiation in capillary hemangioblastoma.
AB  - Seven cases of capillary hemangioblastoma from the cerebellum and spinal cord
      were studied by immunohistochemical methods to determine the origin of the
      stromal cells. A subpopulation of factor XIIIa-positive tumor cells was a
      constant feature in hemangioblastomas. These stellate or spindle-shaped cells
      transformed into typical vacuolated stromal cells. Factor VIII-related antigen
      was limited to the vascular endothelium. Glial fibrillary acidic protein was
      present only in entrapped astrocytes. Staining for alpha-1-antitrypsin (alpha
      1AT) and alpha-1-antichymotrypsin (alpha 1 ACT) was occasionally observed in
      stromal cells. It was concluded that the factor XIIIa-positive stromal cells in
      capillary hemangioblastoma indicate fibrohistiocytic differentiation, which is
      part of the differentiation spectrum of hemangiopericytomas.

PMID- 1351865
TI  - Uniparental isodisomy due to duplication of chromosome 21 occurring in somatic
      cells monosomic for chromosome 21.
AB  - Uniparental disomy has been recently recognized as an important phenomenon in non
      Mendelian inheritance of human genetic disorders. Several mechanisms for
      uniparental disomy, i.e., the presence of two homologous chromosomes derived from
      one parent, have been proposed. We studied two independent cases of abnormalities
      of chromosome 21 in which there were abnormal karyotypes at birth but blood cells
      with normal karyotype predominated later in life, and the cells with
      abnormalities disappeared. Uniparental isodisomy was observed in the normal cells
      in these individuals. The uniparental disomy in these families was the result of
      duplication of a chromosome in mitosis after the loss of the homologous abnormal
      chromosome. The duplication can be seen as mechanism for cell survival and is
      called here "compensatory" isodisomy, which provided a selective advantage for
      the cell population with the normal number of chromosomes 21.

PMID- 1351866
TI  - Nonrandom association between Huntington disease and two loci separated by about
      3 Mb on 4p16.3.
AB  - The gene for Huntington disease (HD) has been localized close to the telomere on
      the short arm of chromosome 4. However, refined mapping using recombinant HD
      chromosomes has resulted in conflicting findings and mutually exclusive candidate
      regions. Previously reported significant nonrandom allelic association between
      D4S95 and HD provided support for a more proximal location for the defective
      gene. In this paper, we have analyzed 17 markers, spanning approximately 6 Mb of
      DNA distal to locus D4S62, for nonrandom association to HD. We confirm the
      previous findings of nonrandom allelic association between D4S95 and HD. In
      addition, we provide new data showing significant nonrandom association between
      HD and 3 markers at D4S133 and D4S228, which are approximately 3 Mb telomeric to
      D4S95.

PMID- 1351867
TI  - A cluster of CpG islands at D10S94, near the locus responsible for multiple
      endocrine neoplasia type 2A (MEN2A).
AB  - We report the characterization of a dense cluster of CpG islands at D10S94 in
      proximal 10q11.2. D10S94 is tightly linked to the gene responsible for multiple
      endocrine neoplasia type 2A (MEN 2A), a dominantly inherited tumor syndrome
      characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and/or
      parathyroid adenoma. To date, no recombinants between D10S94 and MEN2A have been
      identified. The gene(s) responsible for two additional dominantly inherited
      disorders involving cancer of the medullary thyroid, MEN 2B (MEN2B), and
      dominantly inherited MTC without additional clinical features (MTC1), also map to
      this region. The gene or genes responsible for these disorders may be located at
      or near the D10S94 locus. A 570-kb long-range restriction map has been generated
      by pulsed-field gel electrophoresis using probes developed during a 160-kb
      bidirectional cosmid walk at D10S94. Six CpG islands are clustered within a 180
      kb region; five fall within a 145-kb NotI restriction fragment that is contained
      in its entirety in our cosmid contig. The SacII, SfiI, and NotI restriction maps
      for lymphoblast and cloned DNA are concordant. These CpG islands may represent
      the 5' ends of candidate genes for MEN2A, MEN2B, and/or MTC1. One gene designated
      mcs94-1, which is associated with one of the CpG islands in this cluster, has
      been isolated and characterized in detail.

PMID- 1351868
TI  - Identification and characterization of a gene at D10S94 in the MEN2A region.
AB  - We have identified a candidate for the gene responsible for multiple endocrine
      neoplasia type 2A (MEN 2A) at D10S94 in proximal 10q11.2. An evolutionarily
      conserved sequence from D10S94 was used as a probe to isolate cDNAs corresponding
      to a gene that we have termed mcs94-1. The gene spans 11 kb and has an
      unmethylated CpG island at its 5' end. The mcs94-1 transcript is approximately
      2.4 kb in length and is widely expressed. It encodes a putative 415-amino-acid
      polypeptide that is similar in sequence to nucleolin, an abundant nucleolar
      protein. Mcs94-1 was examined as a candidate for MEN2A through nucleotide
      sequence analysis of mcs94-1 exons from an MEN 2A chromosome and its wildtype
      homologue from an MEN 2A patient. The major portion of the expressed mcs94-1
      sequence was examined. No differences in sequence were found between the two
      alleles.

PMID- 1351869
TI  - Genetic mapping of four dinucleotide repeat loci, DXS453, DXS458, DXS454, and
      DXS424, on the X chromosome using multiplex polymerase chain reaction.
AB  - Dinucleotide CA repeat sequences in the human genome have been shown to be highly
      polymorphic due to variation in the length of the repeat-containing segment.
      Therefore, these markers can serve as anchor loci in the construction of a high
      resolution genetic map of the human genome. In this study, we improved the
      efficiency of typing dinucleotide repeats using multiplex polymerase chain
      reaction (PCR). Dinucleotide repeat sequences of four previously identified
      markers (DXS453, DXS458, DXS454, and DXS424) on the long arm of the X chromosome
      were simultaneously amplified in a single PCR reaction. This multiplex PCR was
      applied to genotype individuals from the 40 CEPH reference families, and the
      genotypic data were used to determine the map position of the four loci with
      respect to eight reference markers in the Xq region by linkage analysis.

PMID- 1351870
TI  - Human repeat element-mediated PCR: cloning and mapping of chromosome 10 DNA
      markers.
AB  - Repeat element-mediated PCR can facilitate rapid cloning and mapping of human
      chromosomal region-specific DNA markers from somatic cell hybrid DNA. PCR primers
      directed to human repeat elements result in human-specific DNA synthesis;
      template DNA derived from a somatic cell hybrid containing the human chromosomal
      region of interest provides region specificity. We have generated a series of
      repeat element-mediated PCR clones from a reduced complexity somatic cell hybrid
      containing a portion of human chromosome 10. The cloning source retains the
      centromere and tightly linked flanking markers, plus additional chromosome 10
      sequences. Twelve new inter-Alu, two inter-L1, and four inter-Alu/L1 repeat
      element-mediated PCR clones were mapped by hybridization to Southern blots of
      repeat element-mediated PCR products amplified from somatic cell hybrid DNA
      templates. Two inter-Alu clones mapped to the pericentromeric region. We propose
      that a scarcity of Alu elements in the pericentromeric region of chromosome 10
      contributed to the low number of clones obtained from this region. One inter-Alu
      clone, pC11/A1S-6-c23, defines the D10S94 locus, which is tightly linked to MEN2A
      and D10Z1.

PMID- 1351871
TI  - Human HOX4E: a gene strongly expressed in the adult male and female urogenital
      tracts.
AB  - Homeobox-containing genes (Hox genes) are believed to play a fundamental role in
      development and positional identity. Four homologous Hox gene complexes are found
      in humans and mice. Genes at the 3' ends of these complexes tend to be expressed
      rostrally while those at the 5' end are expressed caudally. Whereas complete open
      reading frames have been reported for rostrally expressed 3' Hox genes,
      structural information is lacking for the more 5' genes. Genomic and cDNA clones
      containing the human HOX4E (also known as human Hox 4.5) gene were isolated. The
      gene contains two exons and spans about 5 kb of DNA. The N-terminal portion of
      the HOX4E activation domain contains several consensus sequence elements also
      found in other mammalian AbdB family genes. Further downstream, however, HOX4E
      contains a novel 37-amino-acid stretch containing 30% acidic residues. Northern
      blot analysis of HOX4E expression in adult tissues showed a major human
      transcript of 1.8 kb, the expression of which was largely limited to tissues of
      the male and female urogenital tracts. Expression was particularly strong in the
      uterus. This suggests that aside from its effects during embryogenesis, the HOX4E
      gene may play a continuing role in adult genitourinary tract function.

PMID- 1351872
TI  - The Mouse Genome Project and human genetics. A report from the 5th International
      Mouse Genome Mapping Workshop, Lunteren, Holland.
AB  - Genome-wide mapping efforts are moving toward the establishment of a 1-cM genetic
      map of the entire mouse genome. The bulk of linkage groups conserved between the
      mouse and the human genomes has been identified. Microsatellite mapping has had a
      major impact on the development of genome-wide genetic maps and, in particular,
      on genome-wide searches for polygenic disease loci. Some substantial regions of
      the mouse genome have a marker density of 1 cM or less and many of these regions
      are now physically mapped. Embryonic YAC contigs have been established in some
      physically mapped regions. A unitary, global mouse mapping database--the Mouse
      Genome Database--is under development along with associated software tools.
      Chromosome committees are having a major impact on the establishment and
      verification of chromosome maps through the preparation of published annual
      reports.

PMID- 1351873
TI  - [Shedding of soluble intercellular adhesion molecule 1 (ICAM-1) from melanoma
      cells and the effect on cellular cytotoxicity].
AB  - ICAM-1-mediated cell-cell adhesion is essential for various immunologic
      functions, including non-MHC-restricted cytotoxicity. Shedding of ICAM-1 occurred
      after stimulation of melanoma cells with TNF alpha and IFN gamma. Soluble forms
      of ICAM-1 inhibited the conjugate formation of NK clones with K562 and of LAK
      cells with melanoma cells. Furthermore, the non-MHC-restricted cytotoxicity
      mediated by NK clones or LAK cells could be abrogated by soluble ICAM-1.

PMID- 1351874
TI  - Intercellular adhesion molecule-1 (ICAM-1) expression by lymph node dendritic
      cells: comparison with epidermal Langerhans cells.
AB  - Following skin sensitization of mice, epidermal Langerhans cells (LC) are
      stimulated to migrate via the afferent lymphatics to the draining lymph nodes.
      Previous studies have demonstrated that, while in transit, LC acquire the
      characteristics of mature dendritic cells (DC) and develop into potent
      immunostimulatory cells. In the present study the expression by LC and lymph node
      DC of intercellular adhesion molecule-1 (ICAM-1) has been compared. Freshly
      isolated LC expressed only very low levels of ICAM-1. In contrast lymph node DC,
      irrespective of whether they were isolated from resting lymph nodes or from
      activated lymph nodes draining the site of sensitization with oxazolone,
      exhibited significant membrane ICAM-1. As a substantial proportion of the DC
      found within the draining nodes of skin sensitized mice derive from epidermal LC
      it is apparent that, during migration from the skin, LC are induced to express
      increased ICAM-1. Such is compatible with the development of LC into effective
      antigen presenting cells.

PMID- 1351875
TI  - PFGE mapping and RFLP analysis of the S/D region of the mouse H-2 complex.
AB  - We have constructed a long range restriction map of the S/D segment of the mouse
      H-2 complex by pulsed field gel electrophoresis and hybridization with mouse cDNA
      probes to Bf and Tnfa genes and human cDNA probes to BAT2, BAT3, BAT4, BAT5, and
      BAT6 genes which have recently been mapped to the human HLA complex between C2
      and HLA-B. The distance between the mouse C2 and Tnfa genes was found to be
      approximately 350 kilobases. The position of the mouse Bat genes in this map were
      found to be comparable to the position of the BAT genes in the human HLA complex.
      A panel of recombinant mouse strains was also examined by restriction fragment
      analysis with probes detecting the Hsp70, Bat5, and Tnfa genes. The results
      indicate that recombination in this segment is not random. No recombinants were
      found with crossovers between the C2 and Hsp70 genes and only one recombinant was
      found with a crossover between Tnfa and H-2D. In contrast, the crossover sites of
      16 recombinants were mapped between the Hsp70 and Tnfa genes. Seven of these
      recombinants were found to have crossovers between Hsp70 and Bat5 and three
      recombinants were found to have crossover sites between Bat5 and Tnfa.

PMID- 1351876
TI  - Strong associations between RFLP and protein polymorphisms for CD46.
AB  - Human CD46 (membrane cofactor protein) is a cell surface glycoprotein with
      cofactor activity for the factor I mediated cleavage of components C3b and C4b.
      Using a CD46 cDNA clone, three restriction enzymes give simple two allele
      restriction fragment length polymorphisms (RFLPs) in samples of over 300
      Caucasians. For Pvu II, P1 with a 16.5 kilobase (kb) fragment and P2 with 14.8 kb
      + 1.9 kb fragments have frequencies of .40 and .60. For Hin dIII, H1 with a 4.3
      kb fragment and H2 with a 2.3 kb fragment have similar frequencies. For Bgl. II,
      B1 with a 10 kb fragment and B2 with 8.3 kb + 1.8 kb fragments have frequencies
      of 0.08 and 0.92. There is strong linkage disequilibrium between these
      polymorphic sites. Designating haplotypes by Hin dIII, Pvu II, Bgl II alleles,
      there are two common haplotypes P2, H2, B2 and P1, H1, B2, expected at
      frequencies of .6 and .32, one less common haplotype P1, H1, B1 expected at a
      frequency .08. The two major protein isoforms of CD46, as detected on peripheral
      blood lymphocytes by western blot, of Mr 66,000 (alpha) and 56,000 (beta) are
      determined by differential splicing in production of the mRNA. A strong
      association between protein isoform and RFLP haplotypes in 30 unrelated subjects
      suggests that the splicing preference site is in linkage disequilibrium with the
      RFLPs. The results are consistent with haplotypes P2, H2, B2 and P1, H1, B1
      producing predominantly alpha; P1, H1, B2 producing predominantly beta in about
      72% of cases and alpha in 28% of cases.

PMID- 1351877
TI  - Plasma cell membrane glycoprotein gene Pca-1 (alkaline phosphodiesterase I) is
      linked to the proto-oncogene Myb on mouse chromosome 10.

PMID- 1351878
TI  - National symposium on child nutrition--the Indian scene.

PMID- 1351879
TI  - pap-and pil-related DNA sequences and other virulence determinants associated
      with Escherichia coli isolated from septicemic chickens and turkeys.
AB  - Escherichia coli isolates from septicemic or healthy chickens and turkeys from
      Quebec were serotyped, examined genotypically by using DNA probes specific for
      the pil and pap fimbrial systems and the aerobactin siderophore system, and
      examined phenotypically for lethality in day-old chicks, hemagglutination, serum
      resistance, and aerobactin production. Serogroups O78 and O1 were most common in
      septicemic chickens and turkeys. pap+ isolates from chickens were associated with
      septicemia, and pap+ isolates from turkeys were associated with lethality in day
      old chicks. Four of nine pap+ isolates from septicemic turkeys expressed P
      adhesin, whereas all pap+ isolates from septicemic chickens were negative for P
      adhesin. The pil+ genotype was associated with septicemia in chickens and with
      serum resistance in isolates from turkeys. Mannose-sensitive hemagglutination of
      guinea pig erythrocytes was associated with septicemia in chickens and turkeys,
      although this phenotype was not associated with pil+ isolates from turkeys. Serum
      resistance was associated with isolates from septicemic turkeys and with
      lethality in isolates from chickens. The aerobactin system was associated with
      isolates from septicemic chickens and turkeys. Overall, results indicated that
      (i) genotypic examination may reveal virulence-associated traits which differ
      from the typically expected phenotype and/or are not readily expressed in vitro,
      and (ii) certain phenotypic and genotypic traits associated with E. coli causing
      extraintestinal disease in humans and animals are also associated with E. coli
      causing avian septicemia.

PMID- 1351880
TI  - Oral vaccination of weaned rabbits against enteropathogenic Escherichia coli-like
      E. coli O103 infection: use of heterologous strains harboring lipopolysaccharide
      or adhesin of pathogenic strains.
AB  - To test the importance of lipopolysaccharide (LPS) and adhesin as major antigens
      in vaccination against rabbit enteropathogenic Escherichia coli (EPEC)-like E.
      coli O103 infection, we used two nonpathogenic wild-type strains to immunize
      rabbits at weaning. One of these strains (C127) harbors the O103 LPS but does not
      express the 32,000-molecular-weight adhesin that characterizes the highly
      pathogenic O103 strains. The other (C6) belongs to the O128 serogroup, which does
      not cross-react with the O103 serogroup, but expresses the adhesin. These strains
      were administered orally, either live or after Formalin inactivation. After
      vaccination, the animals were challenged with highly pathogenic O103 strain B10.
      Compared with rabbits vaccinated with the Formalin-killed homologous strain,
      rabbits vaccinated with killed C127 or C6 showed partial but significant
      protection. When given live, these strains colonized more or less heavily the
      digestive tract of the animals and provided nearly complete (C127) or complete
      (C6) protection against challenge. They induced a quick local immune response, as
      judged by fecal immunoglobulin A anti-LPS kinetics. Furthermore, strain C6
      induced an ecological effect of "resistance to colonization" against challenge
      strain B10. This effect may have been due to the adhesin that is shared by both
      strains and to the production of a colicin. Strain C6 could inhibit in vitro the
      growth of highly pathogenic O103 strains. On the whole, our results show that
      adhesins and LPS are important, although probably not exclusive, protection
      inducing components in rabbit EPEC-like colibacillosis and provide insight into
      possible protection of rabbits against EPEC-like E. coli infection with live
      strains.

PMID- 1351881
TI  - Role of T-lymphocyte subsets in Rhodococcus equi infection.
AB  - Rhodococcus equi, a facultative intracellular gram-positive bacterium, can induce
      life-threatening infections in immunocompromised patients, especially those with
      AIDS. We have studied the mechanism of acquired immunity to this pathogen in a
      murine model. Protective immunity was induced by live but not killed bacteria.
      Adoptive transfer of resistance was obtained with spleen cells but not immune
      serum from mice immunized intravenously 30 days earlier with live bacteria. In
      normal mice, an intravenous challenge of 5 x 10(6) CFU of R. equi was cleared
      from the spleen, liver, and lungs within 3 weeks, whereas athymic nude mice were
      unable to clear the bacteria. In vivo depletion with monoclonal antibodies showed
      that both CD4+ and CD8+ T-cell subsets participate in the clearance of bacteria
      and that CD8+ T cells play the major role.

PMID- 1351882
TI  - Passive protection of suckling infant mice against F41-positive enterotoxigenic
      Escherichia coli strains by intravenous inoculation of the dams with monoclonal
      antibodies against F41.
AB  - Ten monoclonal antibodies (MAbs) against five different epitope clusters of
      adhesion factor F41 (two MAbs per cluster) were tested for protection of infant
      mice against an oral challenge with F41-positive enterotoxigenic Escherichia coli
      (ETEC) B2C and B41M. Infant mice suckling dams intravenously inoculated with MAbs
      were orally challenged, and the survival rates were measured for 12 days after
      inoculation and challenge. Irrespective of their epitope specificity, all F41
      MAbs given in a single dose of 4 mg per dam had a protective effect against both
      ETEC strains. In contrast, one K99 MAb of the same isotype and given in the same
      dose as the F41 MAbs did not protect infant mice at all. A reduction in the dose
      of F41 MAbs to 0.032 mg per dam resulted in a decrease in protection. Two
      different MAbs against the same epitope cluster were not necessarily equally
      protective. Combining MAbs two by two, whether the MAbs recognized the same
      epitope cluster or not, resulted in protective activity essentially similar to
      that obtained with each MAb separately, without any improvement. Therefore, one
      MAb against any epitope may be sufficient for protection. Enzyme-linked
      immunosorbent assay (ELISA) titers of MAbs in the serum of dams were similar,
      irrespective of the epitope specificity of the MAbs, and gradually decreased from
      day 1 to day 12 after inoculation. We found a good correlation between colostrum
      and milk ELISA titers of MAbs and serum ELISA titers of MAbs. Colostrum and milk
      MAb titers were 10-fold lower than corresponding serum MAb titers and stayed high
      until day 5 after inoculation. The most protective MAb had the highest ELISA
      titers in colostrum and milk for the first 5 days after inoculation. ETEC strain
      B2C colonized the intestines of infant mice suckling MAb-inoculated mothers until
      day 12 after challenge. Intestinal levels of the challenge strain were high on
      day 2 but never reached the very high numbers (10(9) to 10(10)) described
      previously in a diarrheic infant mouse model. MAbs did not eliminate the
      challenge ETEC strain from the intestines of infant mice.

PMID- 1351884
TI  - Loss of heterozygosity for distal markers on 22q in human gliomas.
AB  - Loss of constitutional heterozygosity as determined through the analysis of
      restriction-fragment-length polymorphism (RFLP) on tumoral and constitutional DNA
      has proven to be helpful to delimit the location of tumor-suppressor genes in the
      human genome. In malignant gliomas this approach indicates that chromosomes 9p,
      10, 17p, and 22 may contain genes of this category involved in its origin and/or
      progression. Regarding chromosome 22, the data so far provided by molecular
      studies confirmed those previously reported by cytogenetic studies, suggesting
      the existence of a sub-group of malignant gliomas characterized by monosomy of
      this chromosome. However, the precise location of the putative glioma suppressor
      gene on chromosome 22 remains ambiguous. We have performed a combined cytogenetic
      and RFLP study on a series of 31 gliomas, looking for structural abnormalities of
      this chromosome. In 3 instances, terminal deletions of the long arm of chromosome
      22 were observed by both methodologies, suggesting that the band q13 region
      distal to the D22S80 marker might be the critical domain non-randomly involved in
      tumor suppression of gliomas.

PMID- 1351883
TI  - Immunization with Porphyromonas (Bacteroides) gingivalis fimbriae protects
      against periodontal destruction.
AB  - Adhesive fimbriae from Porphyromonas gingivalis are cell surface structures which
      may be important in the virulence of this oral pathogen and thus may serve as a
      critical or target antigen. Immunization with highly purified 43-kDa fimbrial
      protein protected against periodontal tissue destruction when tested in the P.
      gingivalis-infected gnotobiotic rat model. A similarly highly purified 75-kDa
      cell surface component did not provide protection. Heat-killed whole-cell and
      sonicated cell surface extracts which contain the 43-kDa protein as well as the
      75-kDa component were protective also. This study indicates that the fimbrial
      protein may serve as a model for the development of effective vaccines against
      periodontitis, a major human oral disease.

PMID- 1351885
TI  - A combination of two immunotoxins exerts synergistic cytotoxic activity against
      human breast-cancer cell lines.
AB  - In previous studies, combinations of immunotoxins reactive with different cell
      surface antigens have exerted additive cytotoxicity against tumor cells in
      culture. In this report we describe a combination of 2 immunotoxins that produce
      synergistic cytotoxic activity. Recombinantly derived ricin A chain (RTA) was
      conjugated with murine monoclonal antibodies (MAbs) 317G5, 260F9, 454A12 and
      741F8 that bound to cell-surface determinants of 42, 55, 180 (transferrin
      receptor) and 185 kDa (HER-2/neu) expressed by the SKBr3 human breast-cancer cell
      line. When inhibition of clonogenic growth was measured in a limiting dilution
      assay, the combination of 260F9-RTA and 454A12-RTA produced synergistic cytotoxic
      activity against SKBr3 and 2 other breast-cancer cell lines. All other
      combinations produced only additive inhibition of clonogenic growth. Simultaneous
      binding of 260F9 and 454A12 was not supra-additive, but sub-populations of cells
      which lacked one or the other antigen could be detected. Kinetic studies of
      internalization, using antibodies conjugated with gold particles, indicated that
      454A12 remained within peripheral endosomes for a longer interval in the presence
      of 260F9. This change in the traffic of the transferrin receptor may contribute
      to synergy between 260F9-RTA and 454A12-RTA.

PMID- 1351886
TI  - The effect of parity, tumor latency and transplantation on the activation of int
      loci in MMTV-induced, transplanted C3H mammary pre-neoplasias and their tumors.
AB  - Mouse mammary tumor virus (MMTV) infection of mammary glands results in proviral
      insertion into host DNA and activation of cellular genes. Clonal expansion of
      cells bearing insertional mutations results in hyperplastic alveolar nodules
      (HAN) and tumors. HAN, transplanted into epithelium-cleared mammary fat pads,
      form hyperplastic alveolar outgrowths (HOGs). Previous work indicates the
      commonly MMTV-activated genes wnt-1 and int-2 are rarely affected in HOGs and HOG
      derived tumors. To determine the basis of the dichotomy between the frequency of
      wnt/int gene activation in HOG-derived tumors and tumors from breeders of the
      identical inbred mouse strain, we compared the activation of wnt-1, int-2 and int
      3 in tumors from virgin and breeding C3H mice, in consecutive primary tumors
      arising in individual C3H breeders and in C3H HOGs at early passages. Activation
      of wnt-1 or int-2 was rare in HOG-derived tumors (6% and 0%) compared with
      primary tumors in breeders (52% and 14%). int-3 was never found to be activated.
      wnt-1 was activated in the same percentage of primary tumors from virgins as from
      breeders. int-2 was activated only in tumors from breeders. wnt-1 activation also
      did not correlate with shorter tumor latency in multiple tumors from individual
      breeders. wnt-1 RNA was not detected in HOGs at early transplant generations,
      however, low levels of wnt-1 RNA were variably found in the epithelium of virgin
      mammary glands. We cannot explain why C3H HOGs and their derivative tumors
      develop without wnt-1 expression when the majority of C3H primary mammary tumors
      possess an MMTV-activated wnt-1 gene.

PMID- 1351887
TI  - Xamoterol in hypertrophic cardiomyopathy: effects on diastolic function and heart
      rate.
AB  - The aims of this study were to determine the effects of the partial beta 1
      adrenergic agonist, xamoterol, on diastolic function and ambulatory heart rate in
      hypertrophic cardiomyopathy. Eleven patients with non-obstructive hypertrophic
      cardiomyopathy were studied with cross-sectional and Doppler echocardiography and
      24-h Holter monitoring before and after a single intravenous dose of xamoterol.
      Resting heart rate (mean +/- SD) increased from 76 +/- 16 before, to 83 +/- 15
      beats/min 15 min after xamoterol, p = 0.03. In the 4-h period after xamoterol,
      maximum heart rate was reduced (127 +/- 21 to 112 +/- 19, p = 0.01) and minimum
      heart increased (60 +/- 16 to 67 +/- 17, p = 0.04) compared to the same 4-h
      period of the previous day. There were no significant changes in cross-sectional
      or Doppler echocardiographic measurements of left ventricular function following
      xamoterol. Xamoterol stabilises the heart rate in hypertrophic cardiomyopathy.
      The absence of a significant effect on Doppler measurements does not preclude a
      beneficial effect on diastolic function. This initial study suggests that
      xamoterol should be further investigated as a new medical therapy for
      hypertrophic cardiomyopathy.

PMID- 1351889
TI  - V Workshop on Gastroduodenal Pathology and Helicobacter Pylori. Dublin, Ireland,
      July 5-7, 1992. Abstracts.

PMID- 1351888
TI  - The application of nebivolol in essential hypertension: a double-blind,
      randomized, placebo-controlled study.
AB  - This randomized, double-blind, placebo-controlled study investigated the effects
      of nebivolol on blood pressure, plasma renin and vasoactive hormones (aldosterone
      and atrial natriuretic peptide) and the heart (arrhythmias, left ventricular mass
      and ejection fraction) in 32 hypertensive Chinese patients aged 25-65 years.
      Patients received either placebo (3 men, 11 women) or nebivolol 5 mg (5 men, 13
      women) once daily for 4 weeks. In the nebivolol group, a significant decrease in
      blood pressures (P less than 0.001) and heart rate (P less than 0.01) was seen.
      Nebivolol therapy also suppressed plasma renin and aldosterone concentration (P
      less than 0.02) but increased plasma atrial natriuretic peptide levels (P less
      than 0.03). No significant changes in routine blood biochemistry were
      demonstrated in either group. There was a tendency for left ventricular mass to
      decline, and left ventricular ejection fraction to rise during nebivolol therapy,
      but these changes did not reach statistical significance. There was no
      significant change in ectopic activity. None of the 32 subjects had adverse
      experiences requiring cessation of therapy. In conclusion, nebivolol in a dose of
      5 mg daily is effective and well tolerated in patients with essential
      hypertension. It suppresses plasma renin and aldosterone and stimulates plasma
      atrial natriuretic peptide.

PMID- 1351890
TI  - [Mosquito bite allergy].

PMID- 1351891
TI  - [ATPase positive epidermal Langerhans cells: inhibition of ATPase by ammonium
      bituminosulfonate (Ichthyol) and pix lithanthracis].
AB  - Both, ammonium bituminosulfonate (Ichthyol) and Pix lithanthracis reduce the
      number of ATPase-positive epidermal Langerhans cells (ELC) in the epidermis of
      BALB/c mice: vaselinum flavum alone vs vaselinum flavum +5% Ichthyol: P less than
      0.01; vaselinum flavum vs vaselinum flavum +5% Pix lithanthracis: P less than
      0.001. In contrast to this, the number of Ia-positive cells was not changed under
      identical conditions. These results allow the conclusion that Ichthyol and Pix
      lianthracis are able to inhibit the enzyme ATPase on the surface of ELC. We infer
      that inhibition of ELC ATPase may be important in the regulation of ELC function
      (inhibition of cutaneous contact hypersensitivity).

PMID- 1351892
TI  - [Clinical manifestations of HTLV-I infection].

PMID- 1351894
TI  - Abstracts of the XIII Congress, International Society of Biomechanics. Perth,
      Australia, 9-13 December 1991.

PMID- 1351893
TI  - Medical management of inflammatory bowel disease in a spider monkey.
AB  - Inflammatory bowel disease was diagnosed in a 3-year-old, captive-born, hand
      raised, female spider monkey (Ateles geoffroyi). The diagnosis was based on
      clinical signs, positive-contrast radiographic series, endoscopy, histologic
      appearance of intestinal biopsy specimens, and the monkey's response to
      treatment. Treatment consisted of oral administration of prednisone,
      sulfasalazine, and trimethoprim-sulfamethoxazole. Supportive care included a
      bland diet and an electrolyte solution given free choice. Although several
      infective agents were considered, this case illustrates that recurrent enteritis
      in primates may be noninfectious and may respond to anti-inflammatory agents.

PMID- 1351895
TI  - Educators' knowledge and attitudes regarding stimulants in the treatment of
      attention deficit hyperactivity disorder.
AB  - Educators often are asked to provide information regarding students' responses to
      medication used for the treatment of attention deficit hyperactivity disorder
      (ADHD). We designed a questionnaire to determine the knowledge and attitudes of
      educators regarding stimulants. Two hundred ninety-one regular classroom and
      special education teachers in two Ohio school systems received the questionnaire;
      the overall response rate was 65%. Our findings suggest that educators generally
      believe stimulants are useful for students with ADHD and that they frequently
      recommend them to parents. However, educators indicated their knowledge of the
      effects of stimulants was limited and that they had received little education
      about stimulants. Physicians requesting input from educators regarding students
      taking stimulants should be aware of the limitations of educators' knowledge and
      participate in the development of programs to improve that knowledge.

PMID- 1351897
TI  - Neurotensin terminals form synapses primarily with neurons lacking detectable
      tyrosine hydroxylase immunoreactivity in the rat substantia nigra and ventral
      tegmental area.
AB  - A light and electron microscopic double antigen localization technique was
      employed to examine the fine structural relationship between neurotensin
      containing axon terminals and dopaminergic neurons in the substantia nigra and
      ventral tegmental area of the rat. At the light microscopic level, neurotensin
      immunoreactive terminals were densely distributed throughout the substantia nigra
      pars compacta and ventral tegmental area in close proximity to tyrosine
      hydroxylase-immunoreactive somata and dendrites. On electron microscopic
      examination, direct synaptic connections were identified between neurotensin
      immunoreactive axon terminals and tyrosine hydroxylase-immunopositive perikarya
      and dendrites. However, only 8.2% and 8.8% of the neurotensin-immunoreactive
      axonal profiles detected in the substantia nigra and ventral tegmental area,
      respectively, were found in direct apposition with tyrosine hydroxylase
      immunostained elements. In turn, only 9.3% and 10.0% of tyrosine hydroxylase
      immunoreactive dendrites sampled from the substantia nigra and ventral tegmental
      area, respectively, were seen in contact with neurotensin immunopositive axon
      terminals. However, neurotensin-immunoreactive and tyrosine hydroxylase
      immunolabelled elements were frequently identified in close anatomical proximity
      (less than 5 microns) to one another. These results are interpreted in light of
      the selective association of neurotensin receptors with dopaminergic neurons in
      the substantia nigra and ventral tegmental area to suggest a predominantly
      parasynaptic mechanism of action for neurotensin in the ventral midbrain.

PMID- 1351898
TI  - Conference report: the efficacy of caries-preventive strategies.

PMID- 1351896
TI  - Heterogeneous development of calbindin-D28K expression in the striatal matrix.
AB  - In the present study, we attempted to trace the development of the striatal
      matrix by analyzing the ontogenetic expression of calbindin-D28K (calbindin), a
      calcium binding protein selectivity expressed in medium-sized neurons of the
      matrix compartment of the mature rat's caudoputamen. The localization of
      calbindin was documented in a series of developing rat brains, as was the
      compartmental location of these cells relative to tyrosine hydroxylase (TH)
      immunostained dopamine islands, sites of future striosomes. Medium-sized striatal
      neurons appeared in the striatum at embryonic day (E) 20, and from their first
      appearance, the calbindin-positive neurons had highly heterogeneous
      distributions. They first formed a latticework of patches and bands in a ventral
      region of the caudoputamen. By postnatal day (P) 7, this early calbindin-positive
      lattice had evolved into a mosaic in which circumscript pockets of low calbindin
      like immunoreactivity appeared in more extensive calbindin-rich surrounds. With
      further development, the mosaic gradually encroached on all but the dorsolateral
      caudoputamen, a district that is calbindin-poor at adulthood. A special lateral
      branch of the striatal calbindin system was also identified, distinct from the
      rest of the calbindin-positive mosaic in several developmental characteristics.
      In the parts of the caudoputamen where the developing calbindin system and
      dopamine island system were both present, the dopamine islands invariably lay in
      calbindin-poor zones. Most dopamine islands, however, only filled parts of the
      corresponding calbindin-poor zones. Moreover, there were some calbindin-poor
      zones for which TH-positive dopamine islands could not be detected. Thus during
      development, calbindin was expressed in the extrastriosomal matrix of the
      striatum, but the matrix could be divided into calbindin-rich and calbindin-poor
      zones. In the calbindin-rich regions, there were patches of especially intense
      calbindin expression and zones of weaker expression. These results suggest that
      there is neurochemical heterogeneity in the striatal matrix during the prolonged
      developmental period in which the early calbindin-positive lattice expands to
      form the calbindin-positive matrix of the mature striatum. Surprisingly,
      calbindin expression in the matrix, although eventually distributed in strictly
      complementary fashion to striosomes, does not originate as a system complementary
      to dopamine islands. The prolonged disparity between the borders of dopamine
      islands and calbindin-poor zones, and the different spatiotemporal schedules of
      development of the islands and the calbindin gaps suggest instead that the final
      match between the borders of striosomes and surrounding matrix results from
      dynamic processes occurring early in postnatal development. Candidate mechanisms
      for the gradual adjustment of these borders are proposed.

PMID- 1351900
TI  - 25 Years of Immunoenzymatic Techniques. International Congress. Athens, Greece,
      September 9-12, 1991.

PMID- 1351899
TI  - Neuroanatomical evidence that vagal afferent nerves do not possess a high
      affinity uptake system for glutamate.
AB  - The ability of vagal and glossopharyngeal afferent neurons to retrogradely
      transport 3H-D-aspartate from the nucleus tractus solitarius to the nodose and
      petrosal ganglia was examined. Injections of 3H-D-aspartate centered in the
      medial NTS at the rostral-caudal level of the area postrema failed to
      consistently label cells in the nodose and petrosal ganglia. In 5 of the 10 rats
      studied no retrogradely labeled neurons were observed in these ganglia
      ipsilateral to the injection site, while in the other 5 rats a small number of
      cells (less than 3%) were labeled. Injections of 3H-D-aspartate into the NTS
      consistently produced retrograde labeling of neurons in the ipsilateral
      paratrigeminal area. In addition, many heavily labeled neurons were observed in
      the injected as well as the contralateral NTS. Injections of 3H-D-asparate into
      the spinal trigeminal nucleus consistently labeled neurons in the trigeminal
      ganglion. Since the uptake and retrograde transport of 3H-D-aspartate appears to
      be characteristic of neurons that use glutamate or aspartate as a
      neurotransmitter, these results suggest that vagal and glossopharyngeal afferents
      are not glutamatergic or aspartatergic.

PMID- 1351901
TI  - Radiation-induced heart disease: review of experimental data on dose response and
      pathogenesis.
AB  - Clinical and experimental heart irradiation can cause a variety of sequelae. A
      single dose of greater than or equal to 15 Gy leads to a reversible exudative
      pericarditis, occurring in dogs, rabbits or rats at around 100 days. Its time
      course is very similar in all species investigated, but there are considerable
      species and strain differences in severity and incidence. After longer, dose
      dependent latency times chronic congestive myocardial failure develops. At
      histological examination myocardial degeneration and necrosis is observed, which
      in some species is accompanied by a variable degree of interstitial fibrosis. In
      rabbits and rats, myocardial degeneration becomes apparent at around 70 days
      after 20 Gy and is preceded by a marked reduction in capillary density as well as
      ultrastructural endothelial cell degeneration. Simultaneously to structural
      capillary damage, a focal loss of the endothelial marker enzyme alkaline
      phosphatase was observed in rats in areas with subsequent myocardial
      degeneration. Cell kinetic studies in rabbits and rats revealed a radiation
      induced wave of increased endothelial cell proliferation at 30-100 days
      postirradiation. In the rat it is exclusively seen in conjunction with alteration
      of endothelial cell marker enzymes. The temporal and spatial pattern of
      proliferative response exludes endothelial cell death in mitosis as the sole
      pathogenetic mechanism causing capillary loss and myocardial degeneration.
      Parallel to development of morphological damage, haemodynamic studies in various
      rats strains revealed a drop in cardiac output and left ventricular ejection
      fraction to about 64% of normal values after 20 Gy. In vivo, this slightly
      reduced cardiac function was then maintained in a steady state for many weeks,
      probably due to a compensatory up-regulation of cardiac beta-adrenergic
      receptors. In denervated working heart preparations in vitro, however, these
      compensatory mechanisms are not effective and stroke volume as well as cardiac
      contractility show a rapid and steady deterioration. In many respects radiation
      induced heart disease conforms to radiobiological concepts of late-responding
      tissues, showing a chronic progressive time-course and a very pronounced
      fractionation effect. However, pathogenesis cannot be understood in terms of
      target cell depletion alone, and experimental evidence indicates the importance
      of alterations of regulatory mechanisms.

PMID- 1351902
TI  - Mutagenic and transforming effects of soft-X-rays with resonance energy of
      phosphorus K-absorption edge.
AB  - Syrian golden hamster embryo (SHE) cells were exposed to synchrotron-produced
      monochromatic X-rays at 5.747 (2.159 keV), 5.763 (2.153 keV) and 5.779 A (2.147
      keV). Although X-rays of all wavelengths induced mutations and chromatid
      aberrations in a dose-dependent manner, when cells were irradiated with 2.153 keV
      X-rays, which correspond to the resonance energy of the phosphorus K-absorption
      edge, the frequencies of mutation and chromatid aberration at equal dose levels
      were higher than for X-rays of the other wavelengths. At equal survival levels,
      however, there was no difference in the frequencies of mutations and chromatid
      aberrations in cells irradiated with soft X-rays. On the other hand, the
      frequency of morphological transformation in cells irradiated with 2.147 keV X
      rays was higher than those irradiated with 2.153 keV and 2.159 keV X-rays. The
      relative biological effectiveness compared to cobalt-60 gamma-rays in
      morphological transformation was 2.8 for 2.147 keV, 1.1 for 2.159 keV and 1.0 for
      2.153 keV at a 37% survival level.

PMID- 1351903
TI  - Gamma-irradiated DNA activates histone H1-specific proteinase of rat liver
      nuclei.
AB  - We investigated the effect of various forms of DNA (double- and single-stranded
      calf thymus DNA, circular plasmid DNA, gamma- and UV-irradiated DNA and DNAase I
      treated double-stranded DNA) aggregated with histones, on the proteolysis of
      these histones by proteinase associated with the rat liver nuclear scaffold. It
      was shown that the nuclear scaffold-associated proteinase is able to degrade
      selectively the histone H1 only in the presence of the DNA containing single
      strand breaks induced by gamma-radiation or DNAase I treatment as well as in the
      presence of heat-denatured DNA. This proteinase is not activated by the double
      stranded circular plasmid DNA or by UV-treated double-stranded DNA. Histone H1
      specific proteinase (HSP) activated by gamma-irradiated DNA is inhibited by
      inhibitors of serine proteinases such as antipain, leupeptin,
      phenylmethylsulphonyl fluoride, as well as by dithiothreitol. The results lead us
      to suggest that DNA-activated HSP from rat liver nuclei is involved in the
      regulation of the access of repair enzymes to the damage portions of DNA within
      chromatin.

PMID- 1351904
TI  - Measurement of radiation-induced damage to DNA at the molecular level.

PMID- 1351905
TI  - 2-deoxy-D-glucose inhibits rejoining of radiation-induced DNA double-strand
      breaks in yeast.
AB  - Effects of 2-deoxy-D-glucose (2-DG) on radiation-induced DNA double-strand breaks
      (dsb) have been studied under non-growth conditions in a respiratory-deficient
      strain of the yeast Saccharomyces cerevisiae. Velocity sedimentation in neutral
      sucrose gradients was used to measure DNA dsb. Addition of 2-DG to the liquid
      holding medium (67 mM phosphate buffer, pH 5, 30 degrees C) at an equimolar
      concentration with glucose (50 mM) reduced the rate and extent of dsb rejoining.
      The inhibition of rejoining mediated by 2-DG is reversible for the majority--but
      not all--of the radiation-induced dsb.

PMID- 1351906
TI  - Effect of aphidicolin on DNA synthesis, PLD-recovery and DNA repair of human
      diploid fibroblasts.
AB  - The effect of aphidicolin, a specific inhibitor of DNA polymerases alpha and
      delta, was studied on DNA synthesis, PLD-recovery and DNA double-strand break
      rejoining in X-irradiated human fibroblasts. In unirradiated, exponentially
      growing cells, aphidicolin (0.5-5 micrograms ml) inhibited DNA synthesis almost
      completely. This effect depended not only on aphidicolin concentration but also
      on the duration of pre-incubation. The action of aphidicolin was found to be
      reversible. When aphidicolin had been removed, colony forming ability was not
      affected in aphidicolin pretreated cells. Aphidicolin pretreated and irradiated
      cells showed a reduction in PLD-recovery, dependent on aphidicolin concentration
      and duration of pretreatment. The initial number of DNA double-strand breaks
      (calibrated by 125I decay) was not affected by aphidicolin. However, after
      incubation for 90 min in the presence of aphidicolin there was a large reduction
      in double-strand break rejoining. With long incubation periods in aphidicolin
      rejoining was almost completely inhibited.

PMID- 1351907
TI  - Frequencies of X-ray-induced chromosome translocations in human peripheral
      lymphocytes as detected by in situ hybridization using chromosome-specific DNA
      libraries.
AB  - In situ hybridization with chromosome-specific DNA libraries was used to analyse
      radiation-induced stable translocations in human peripheral blood lymphocytes.
      These data were compared with radiation-induced unstable-type aberrations
      (dicentrics) in the same samples. The results indicate that far more stable
      aberrations are induced by radiation in comparison to unstable aberrations.

PMID- 1351908
TI  - Induced accumulation of polyubiquitin gene transcripts in HeLa cells after UV
      irradiation and TPA-treatment.
AB  - There are three species of ubiquitin gene transcripts in HeLa cells, termed UbA
      (approximately 0.7 kb), UbB (approximately 1.1 kb) and UbC (approximately 2.5
      kb). In the present report, the UbC transcript was shown to accumulate up to 2.5
      fold after irradiation with UV light or treatment with the phorbol ester 12-O
      tetradecanoyl-phorbol-13-acetate (TPA). The kinetic analysis indicated that the
      induced accumulation of UbC was rapid and transient; maximal accumulation of UbC
      was induced at 2.5 h after UV irradiation or 3 h after TPA treatment. Inhibition
      of a de novo protein synthesis by cycloheximide did not repress the induction of
      UbC after treatment with UV light and TPA. On the other hand, induction of UbA
      and UbB, in most cases, was not observed. UV-inducibility of human ubiquitin
      conjugating enzyme, E2(17k), was also tested. E2(17k) is a protein with high
      sequence similarity to the product of yeast DNA repair gene, RAD6. While the RAD6
      gene has been reported to be inducible by UV light, no change in E2(17k) gene
      transcript was observed after UV irradiation.

PMID- 1351909
TI  - DNA damage induced by hypocrellin-A photosensitization.
AB  - Hypocrellin-A (HC-A) isolated from Hypocrellia bambusae Sacc., is a new and
      effective photosensitizer. Illumination of sarcoma 180 cells with visible light
      in the presence of HC-A leads to a decrease in cell viability and 3H-TdR
      incorporation, causes DNA strand breakage, and results in the selective
      destruction of guanine moieties in DNA. HC-A photosensitization causes an
      increase in the theta 260/theta 280 ratio in the circular dichroism spectra of
      DNA in vitro. Of the four usual 2'-deoxynucleotides illuminated in the presence
      of HC-A only 2'-deoxyguanylic acid was destroyed.

PMID- 1351910
TI  - Effect of heat on induction and repair of DNA strand breaks in X-irradiated CHO
      cells.
AB  - Chinese hamster ovary cells were exposed to various heat treatments followed by X
      irradiation, and the induction and repair of DNA strand breaks was studied using
      the alkaline unwinding technique. Heat treatments alone were found to cause DNA
      strand breakage only for temperatures greater than or equal to 43 degrees C,
      whereas the number of radiation-induced strand breaks was unaffected by
      additional heating. Strand break repair was studied for irradiated cells
      preheated at temperatures ranging from 42 degrees C to 45 degrees C. The total
      repair curve could be separated into three phases, a fast (t = 0-15 min), an
      intermediate (t = 15-120 min) and a slow (t greater than or equal to 120 min)
      phase. All phases were altered when cells were heated either prior to or after
      irradiation. The fast and the intermediate phase could be well interpreted by the
      assumption that irradiation leads to both primary and secondary single-strand
      breaks, the latter being generated by enzymatic incision at sites of damaged
      bases. For irradiation alone, the ratio of all secondary strand breaks to all
      primary breaks was fsec = 1.5 +/- 0.5. This ratio was not altered by preceding
      heat treatments (mean fsec = 1.7 +/- 0.2). The main effect of heating on the
      repair kinetics of single-strand breaks was an increase in the repair half-time
      of primary and secondary breaks (maximum increase by a factor of 3.4), whereas
      the generation of secondary breaks was only slightly retarded (factor 1.3). The
      slow repair phase, which is assumed to represent the repair of DNA double-strand
      breaks, was best described by a single exponential component. The half-time of
      this component was found to increase from tau slow = 170 +/- 70 min for non
      heated cells to tau slow = 345 +/- 80 min for cells heated at 45 degrees C for 20
      min, indicating that heat inhibited the repair of double-strand breaks. For
      irradiation alone, the initial fraction of the slow component was fslow = 0.065
      +/- 0.004. This fraction was enhanced by additional heating, with a maximum
      increase by a factor of 2.7 for cells heated at 45 degrees C for 20 min. This
      elevation cannot be the result of an enhanced induction of double-strand breaks,
      but must be associated with an additional formation of slowly repaired strand
      breaks during repair incubation. These additional strand breaks must arise from
      strand breaks which in non-heated cells are repaired during the fast or
      intermediate phase.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1351911
TI  - Effect of thermotolerance and step-down heating on thermal radiosensitization in
      CHO cells.
AB  - Chinese hamster ovary cells were exposed to single or fractionated heat
      treatments followed by irradiation on ice with graded doses of X-rays. The dose
      response curves obtained were fitted by the linear-quadratic equation -ln(S/S0) =
      alpha D + beta D2 and analysed in terms of TER10%, alpha and beta. Thermal
      enhancement ratio, TER10%, was reduced when heat sensitivity was lowered either
      by chronic (pretreatment 40 degrees C, 16 h) or acute (43 degrees C, 45 min-37
      degrees C, 10 h) thermotolerance, but was enhanced after step-down heating (43-40
      degrees C or 45-40 degrees C). It could be shown that thermal radiosensitization,
      as expressed by TER10%, is modified by thermotolerance or step-down heating only
      to the extent to which cellular survival is modified by the corresponding
      pretreatments. However, the relative change of alpha and beta was found to be
      different for thermotolerance and step-down heating. For thermotolerant cells the
      values for alpha and beta were reduced by about the same factor, whereas step
      down heating caused an increase in both parameters, which was greater for alpha
      than for beta. Data analysis showed that the modification of thermal
      radiosensitization by thermotolerance can be interpreted as if the cells were
      heated at the given temperature for a shorter time, whereas after step-down
      heating the cells responded as if they were exposed to a higher temperature prior
      to irradiation.

PMID- 1351912
TI  - A role for calcium in regulating apoptosis in rat thymocytes irradiated in vitro.
AB  - Thymus-derived lymphocytes undergo death after gamma-irradiation via a pathway
      termed apoptosis, or programmed cell death. An early step in this pathway is the
      production of nucleosome-sized fragments of DNA. DNA fragmentation was used as
      the endpoint in these investigations to examine apoptosis in lymphocytes
      extracted from the rat thymus and irradiated in vitro. In unirradiated thymocytes
      the level of DNA fragmentation rose to 15% by the first hour of culture, where it
      remained approximately constant until the fifth hour. In contrast, thymocytes
      irradiated with a dose of 2.5 Gy exhibited a large and dramatic increase in DNA
      fragmentation beginning 2 h postirradiation. DNA fragmentation measured 6 h after
      irradiation was detected after as little as 0.25 Gy and reached a maximum of 90%
      with 10 Gy. Metabolic control of DNA fragmentation after irradiation was
      evidenced by the suppression of DNA fragmentation when thymocytes were incubated
      with cyclohexamide or actinomycin D. When gamma-irradiated thymocytes were
      incubated with the Ca2+ chelator EGTA, DNA fragmentation was reduced
      significantly. BAPTA-AM, a highly specific intracellular Ca2+ chelator,
      essentially eliminated DNA fragmentation in cells irradiated with 2.5 Gy and,
      unlike EGTA, eliminated the background level of fragmentation in unirradiated
      samples. Therefore, our data are consistent with the possibility that Ca2+ serves
      as a second messenger to induce DNA fragmentation in irradiated thymocytes,
      suggesting a common pathway for cells prompted to enter apoptosis from seemingly
      dissimilar interval events.

PMID- 1351913
TI  - Effect of TPA, okadaic acid and 1 alpha,25-dihydroxyvitamin D3 on neoplastic
      transformation induced by 60Co gamma-rays or 252Cf fission neutrons in Balb/c 3T3
      cells.
AB  - The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), 1 alpha,25
      dihydroxyvitamin D3 [1 alpha,25(OH)2D3] and okadaic acid were individually
      examined on the neoplastic transformation of Balb/c 3T3 cells which were exposed
      to either 60Co gamma-rays or 252Cf fission neutrons. The addition of 1
      alpha,25(OH)2D3, or TPA, enhanced the transformation induced by gamma-rays or low
      doses of fission neutrons. No enhancement was observed by the addition of okadaic
      acid except at toxic concentrations (5 ng/ml) and with higher doses of radiation.
      Moreover, the enhancement of transformation by either 1 alpha,25(OH)2D3 or TPA
      decreased as the radiation dose was increased. The enhancement ratio, calculated
      by least-square analysis from 0 Gy to 1 Gy, was greater for 1 alpha,25(OH)2D3
      than for TPA, and also greater for gamma-ray irradiation than for neutron
      irradiation. These results suggest that the promotion of radiation-induced
      transformation depends on the level of the initial damage caused by radiation;
      and that the differences in the enhancement properties of different chemicals may
      be due to different individual triggering mechanisms involved in the
      transformation process.

PMID- 1351914
TI  - Comment on mechanism of radiation effects with special reference to
      transformation.

PMID- 1351915
TI  - Linear quadratic model of radiocurability on multicellular spheroids of human
      lung adenocarcinoma LCT1 and mouse fibrosarcoma FSA.
AB  - The LCT1 cells derived from a human lung adenocarcinoma and the FSA cells from a
      mouse fibrosarcoma were found to form spheroids. The cure-dose relationship of
      spheroids and the survival curves of their component cells were analysed by using
      a linear-quadratic model for cell survival and a Poisson distribution for cure.
      The analysis resulted in three conclusions: (1) the double minus logarithm of
      cure probability was linearly related to radiation dose, (2) the critical cell
      number was constant at any given cure probability, and (3) cellular
      radiosensitivity was also constant. The experiments seem to meet these conditions
      for each of two kinds of spheroids. Control doses (50%) were 20 Gy for LCT1
      spheroids and 21 Gy for FSA spheroids, both 400 microns in diameter. The analysis
      showed that the lower cellular radiosensitivity and the higher number of
      clonogenic cells made LCT1 spheroids more radioresistant than FSA spheroids and
      that the higher critical number of 130 cells made the LCT1 spheroids more
      sensitive than the FSA spheroids with 18 such cells. The overall radiocurability
      of spheroids was a result of these three opposing effects, indicating that the
      critical cell number can be one important factor in determining the
      radiocurability of multicellular systems.

PMID- 1351916
TI  - Contrasting dose-rate effects of gamma-irradiation on rat salivary gland
      function.
AB  - The aim of this study was to investigate the effects of 60Co irradiation
      delivered at high (HDR) and low (LDR) dose-rates on rat salivary gland function.
      Total-body irradiation (TBI; total doses 7.5, 10 and 12.5 Gy) was applied from a
      60Co source at dose-rates of 1 cGy/min (LDR) and 40 cGy/min (HDR) followed by
      syngeneic bone marrow rescue. Four days before and 1-30 days after TBI,
      submandibular and parotid saliva samples were collected in male albino Wistar
      rats using Lashley cups. Lag phase and flow rate were recorded, and [Na+] and
      [K+] were measured. The severity of salivary gland dysfunction for each dose-rate
      was dependent on total TBI dose in all parameters. LDR irradiation significantly
      enhanced the increase of lag phase, while it tended to further decrease flow rate
      during days 0-3. At later times the reverse effect was seen with significant LDR
      sparing in most cases. The changes in [Na+] and [K+] showed similar trends; LDR
      had an enhancing effect for early damage, while beyond day 3 it consistently
      produced less damage. From this dose-rate study it is concluded that the early
      postirradiation changes in salivary gland function are probably predominantly
      caused by irradiation damage to membrane structures and are less the result of
      reproductive failure. The later changes in salivary gland function are probably
      mainly dependent on repopulation of surviving stem cells.

PMID- 1351917
TI  - Pharmacologic adjunctive therapy for acute myocardial infarction.
AB  - Thrombolysis and PTCA offer reperfusion for limiting infarct size and reducing
      mortality in acute myocardial infarction patients. Heparin, aspirin, nitrates,
      beta-blockers and calcium antagonists are very important in supplementing these
      two primary reperfusion modes. The adjunctive role of these five pharmacologic
      agents is discussed.

PMID- 1351918
TI  - Effect of divalent cations on adhesion of polymorphonuclear leukocytes to matrix
      molecules in vitro.
AB  - Adhesion of N-formyl-methionyl-leucylphenylalanine-stimulated human
      polymorphonuclear leukocytes (PMNs) to dishes coated with laminin, fibronectin,
      or collagen types I and IV was dependent on the presence of magnesium (Mg2+) but
      not calcium (Ca2+). Addition of manganese (Mn2+) in combination with Ca2+ and
      Mg2+ further increased the number of PMNs adhering to the matrix proteins.
      Monoclonal antibody 60.3 (mAb 60.3) was equally effective at inhibiting adhesion
      of PMNs to all the matrix proteins. The presence of Mn2+ (50 microM), in addition
      to 1 mM Ca2+ and Mg2+, required higher concentrations of mAb 60.3 to inhibit
      adhesion of PMNs to collagens type I or IV, suggesting increased affinity of PMNs
      for these substrates. These findings suggest that the PMNs may regulate the
      affinity of CD11/CD18 for multiple ligands by binding different divalent cations
      to the receptor.

PMID- 1351919
TI  - Vitamin A deficiency and glucocorticoid receptor activity in rat liver.
AB  - The influence of vitamin A on the binding properties of hepatic glucocorticoid
      receptors (GR) was studied in young rats 7 weeks after they had been given a diet
      with or without vitamin A. Scatchard analysis showed an increased capacity of
      cytosolic GRs to bind dexamethasone in vitamin A deficiency. In these rats, an
      increase in tyrosine aminotransferase also occurred, and this could be related to
      the increased formation of hormone-GR complexes. Measurement of protein kinase C
      activity showed an increase which might be related to the functional activity of
      GRs.

PMID- 1351920
TI  - The CD3 zeta cytoplasmic domain mediates CD2-induced T cell activation.
AB  - CD2-mediated T lymphocyte activation requires surface expression of CD3-Ti, the T
      cell receptor (TCR) for antigen major histocompatibility complex protein. Given
      the importance of CD3 zeta in TCR signaling, we have directly examined the
      ability of the CD3 zeta cytoplasmic domain to couple CD2 to intracellular signal
      transduction pathways. A cDNA encoding a chimeric protein consisting of the human
      CD3 zeta cytoplasmic domain (amino acid residues 31-142) fused to the CD8 alpha
      extracellular and transmembrane domains (amino acid residues 1-187) was
      transfected into a CD2+CD3-CD8- variant of the human T cell line Jurkat. The
      resulting transfectants expressed the CD8 alpha/CD3 zeta chimeric receptor at the
      cell surface in the absence of other TCR subunits. Stimulation of these
      transfectants with anti-T11(2) + anti-T11(3) monoclonal antibodies (mAbs)
      initiated both a prompt cytosolic free calcium ([Ca2+]i) rise and protein
      tyrosine kinase activation. Stimulation with either intact anti-T11(2) + anti
      T11(3) mAbs or purified F(ab')2 fragments resulted in interleukin 2 (IL-2)
      secretion. In contrast, control cell lines transfected with a cDNA encoding wild
      type CD8 alpha, and thus lacking surface expression of the CD3 zeta cytoplasmic
      domain, failed to show any [Ca2+]i rise, protein tyrosine kinase activation, or
      IL-2 secretion after identical stimulation. These data directly establish the CD3
      zeta cytoplasmic domain as a necessary and sufficient component of the CD3-Ti
      complex involved in T lymphocyte activation through CD2. Moreover, they show that
      CD2 signaling can function in the absence of Fc receptors.

PMID- 1351921
TI  - Murine thymic CD4+ T cell subsets: a subset (Thy0) that secretes diverse
      cytokines and overexpresses the V beta 8 T cell receptor gene family.
AB  - We demonstrate here the presence of a distinct mature CD4+8- T cell subset in
      mouse thymus. This subset, termed "Thy0," is delineated by the absence of 3G11
      expression from about half of the 6C10-/HSAlow/- fraction of CD4+8- thymic cells.
      Thy0 is detectable from the neonatal period and largely contributes the Th0-type
      diverse cytokine production previously reported for the HSAlow/-CD4+ thymic
      population. Further, cells expressing the T cell receptor V beta 8 gene family
      are found at increasing frequency in Thy0 with age, comprising 40-60% of Thy0 in
      adult BALB/c mice. This alteration of V beta 8+ cell frequency is unique to Thy0,
      since no other CD4+ subset in thymus or spleen shows such V beta 8 overusage. All
      functional CD4+ T cell subsets, including Thy0, show appropriate V beta clonal
      deletion associated with endogenous superantigens. Thus, it appears that Thy0 is
      an intrathymically generated secondary cell subset produced after CD4+ T cell
      selection.

PMID- 1351922
TI  - In vivo cellular tropism of human T cell leukemia virus type II (HTLV-II).
AB  - To investigate the in vivo cellular tropism of human T cell leukemia virus type
      II (HTLV-II), subpopulations of fresh peripheral blood mononuclear cells from
      infected individuals were isolated and analyzed by polymerase chain reaction for
      the presence of provirus. In eight of nine patients, HTLV-II was detected
      exclusively in the CD8+ T lymphocyte population. In the remaining patient,
      provirus was also detected in CD4+ T lymphocytes. Provirus was not detected in B
      lymphocytes or monocytes of any patient. These results suggest that in vivo HTLV
      II has a preferential, and perhaps in some cases, an exclusive tropism for CD8+ T
      lymphocytes. The findings contrast sharply with those on HTLV-I where there is a
      preferential tropism for CD4+ T lymphocytes. Although HTLV-II infection has not
      been consistently associated with any lymphoproliferative disorders, the results
      suggest that if these occur, they may be different from those known to be
      associated with HTLV-I.

PMID- 1351923
TI  - Protein phosphorylation in bovine adrenal medullary chromaffin cells: histamine
      stimulated phosphorylation of tyrosine hydroxylase.
AB  - Histamine can cause the release of catecholamines from bovine adrenal medullary
      chromaffin cells by a mechanism distinct from that of the depolarizing agents
      nicotine or high K+ buffer. It was the aim of this study to determine the protein
      phosphorylation responses to histamine in these cells and to compare them with
      those induced by depolarization. A number of proteins showed increases in
      phosphorylation in response to histamine especially when analyzed on two
      dimensional polyacrylamide gel electrophoresis or by phosphopeptide mapping; one
      protein of 20,000 daltons was markedly dephosphorylated. Emphasis was given to
      the effects of histamine on tyrosine hydroxylase (TOH) phosphorylation, because
      this protein showed the most prominent changes on one-dimensional gels. Histamine
      acted via H1 receptors to increase TOH phosphorylation; the response was blocked
      by the H1 antagonist mepyramine and could be mimicked by the H1 agonist
      thiazolylethylamine, but not by the H2 agonist dimaprit. The H3 agonist (R) alpha
      methylhistamine increased TOH phosphorylation at high concentrations, but the
      response was blocked entirely by mepyramine. Histamine rapidly increased the
      phosphorylation of TOH, with a maximum reached within 5 s and maintained for at
      least 30 min. This was in marked contrast to nicotine-stimulated protein
      phosphorylation of TOH, which was rapidly desensitized. The initial
      phosphorylation response to histamine was independent of extracellular Ca2+ for
      at least 3 min, but the sustained response required extracellular Ca2+. This was
      in contrast to the situation with both nicotine and high K+ buffer, which under
      the conditions used here caused a response which was dependent on extracellular
      Ca2+ at all times investigated. In the presence of histamine, the phosphopeptide
      profiles for TOH were essentially the same with or without Ca2+, suggesting that
      the same protein kinases were involved, but at longer times there was evidence of
      new phosphorylation sites. The mechanism or mechanisms whereby histamine
      modulates TOH phosphorylation are discussed with emphasis on the differences from
      depolarizing agents.

PMID- 1351924
TI  - Screening of thiol compounds: depolarization-induced release of glutathione and
      cysteine from rat brain slices.
AB  - Superfusates from rat brain slices were screened for thiol compounds after
      derivatization with monobromobimane by reversed-phase HPLC. Only glutathione and
      cysteine were detected. The Ca(2+)-dependent release of these compounds from
      slices of different regions of rat brain was investigated, applying a highly
      sensitive and reproducible quantification method, based on reduction of
      superfusates with dithiothreitol, reaction of thiols with iodoacetic acid,
      precolumn derivatization with o-phthalaldehyde reagent solution, and analysis
      with reversed-phase HPLC. This methodology allowed determination of reduced and
      total thiols in aliquots of the same superfusates. Mostly reduced glutathione and
      cysteine were released upon K+ depolarization and the Ca2+ dependency suggests
      that they originate from a neuronal compartment. The GSH release was most
      prominent in the mesodiencephalon, cortex, hippocampus, and striatum and lowest
      in the pons-medulla and cerebellum. This underscores a physiologically
      significant role for glutathione in CNS neurotransmission.

PMID- 1351925
TI  - Somatostatin content increases following norepinephrine depletion in frontal
      cortex of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice.
AB  - The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on
      somatostatin (SS)-containing neurons were examined by measuring dopamine,
      norepinephrine (NE), SS, and SS mRNA in striatum and frontal cortex of C57/B16
      mice at various times following treatment with MPTP-HCl (96 mg/kg i.p.). MPTP
      caused a 70% depletion of dopamine in striatum by 1 day and a 40% depletion of NE
      in frontal cortex within 3 days. SS content was increased in frontal cortex 4
      days later, but not in striatum; there were no changes in SS mRNA. Maprotiline, a
      specific NE-uptake blocker, prevented both the depletion of NE and the increase
      of SS in frontal cortex due to MPTP administration. These results support the
      possibility that NE can regulate SS in frontal cortex and are discussed in terms
      of the decrease of SS seen in parkinsonian patients with dementia.

PMID- 1351926
TI  - Pharmacological characterization and autoradiographic localization of histamine
      H2 receptors in human brain identified with [125I]iodoaminopotentidine.
AB  - 125I-Aminopotentidine (125I-APT), a reversible probe of high specific
      radioactivity and high affinity and selectivity for the H2 receptor, was used to
      characterize and localize this histamine receptor subtype in human brain samples
      obtained at autopsy. On membranes of human caudate nucleus, specific 125I-APT
      binding at equilibrium revealed a single component, with a dissociation constant
      of 0.3 nM and maximal capacity of about 100 fmol/mg of protein. At 0.2 nM, 125I
      APT specific binding, as defined with tiotidine, an H2-receptor antagonist
      chemically unrelated to iodoaminopotentidine, represented 40-50% of the total.
      Specific 125I-APT binding was inhibited by a series of typical H2-receptor
      antagonists that displayed apparent dissociation constants closely similar to
      corresponding values at the reference biological system, i.e., guinea pig atrium.
      This indicates that the pharmacology of the H2 receptor is the same in the human
      brain as on this reference system. However, histamine was about 10-fold more
      potent in inhibiting 125I-APT binding to membranes of human brain than of guinea
      pig brain. 125I-APT binding was also inhibited by amitriptyline and mianserin,
      two antidepressant drugs, in micromolar concentrations corresponding to effective
      plasma concentrations of treated patients. The distribution of H2 receptors was
      established autoradiographically with 125I-APT on a series of coronal sections of
      human brain after assessing the pharmacological specificity of the labeling. The
      highest density of 125I-APT sites was found in the basal ganglia, various parts
      of the limbic system, e.g., hippocampus or amygdaloid complex, and the cerebral
      cortex. H2 receptors displayed a laminar distribution in cerebral cortex and
      hippocampal formation. A low density of sites was found in cerebellum as well as
      in hypothalamus, the brain area where all the perikarya and the largest number of
      axons of histaminergic neurons are found. The widespread distribution of H2
      receptors in the human brain is consistent with the alleged modulatory role of
      histamine mediated by this subtype of receptor.

PMID- 1351927
TI  - In vivo partial inactivation of dopamine D1 receptors induces hypersensitivity of
      cortical dopamine-sensitive adenylate cyclase: permissive role of alpha 1
      adrenergic receptors.
AB  - As shown by autoradiography, peripheral injections of N-ethoxycarbonyl-2-ethoxy
      1,2-dihydroquinoline (EEDQ) induced a dose-dependent decrease of [3H]SCH 23390
      and [3H]prazosin high-affinity binding sites in the rat prefrontal cortex. EEDQ
      showed similar efficacy in inactivating cortical and striatal dopamine (DA) D1
      receptors, whereas prazosin-sensitive alpha 1-adrenergic receptors were more
      sensitive to the action of the alkylating agent, as for all doses of EEDQ tested
      (from 0.8 to 3 mg/kg, i.p.), the decrease in cortical [3H]SCH 23390 binding was
      less pronounced than that of [3H]prazosin. The effects of EEDQ on [3H]SCH 23390
      binding and DA-sensitive adenylate cyclase activity were then simultaneously
      compared in individual rats. In the striatum, whatever the dose of EEDQ used, the
      decrease of DA-sensitive adenylate cyclase activity was always lower than that of
      D1 binding sites, suggesting the occurrence of a large proportion of spare D1
      receptors. In the prefrontal cortex, a significant increase in DA-sensitive
      adenylate cyclase activity was observed in rats treated with a low dose of EEDQ
      (0.8 mg/kg), this effect being associated with a slight reduction in [3H]SCH
      23390 binding sites (-20%). Parallel decreases in the enzyme activity and D1
      binding sites were observed with higher doses. The EEDQ-induced supersensitivity
      of DA-sensitive adenylate cyclase did not occur in rats in which the decrease in
      [3H]prazosin binding sites was higher than 35%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351928
TI  - Dopamine depletion preferentially impairs D1- over D2-receptor regulation of
      striatal in vivo acetylcholine release.
AB  - The roles of D2 and D1 dopaminergic receptors on the regulation of striatal
      acetylcholine (ACh) release in vivo were examined for a period of 120 min after
      acute (2 h) or prolonged (16 h) depletion of brain dopamine (DA) by alpha-methyl
      p-tyrosine. The reduction of DA transmission did not affect basal ACh output
      after 2 h but markedly lowered ACh release by 16 h (50%). Acute alpha-methyl-p
      tyrosine pretreatment prevented the reduction of ACh release by the D1 antagonist
      SCH 23390 and its increase by the D2 antagonist, remoxipride, consistent with a
      drastic reduction of DA transmission at both DA receptors. However, 16 h after
      alpha-methyl-p-tyrosine, the effect of remoxipride on ACh release was restored,
      but SCH 23390 still had no effect, suggesting that the D2 inhibitory tone on ACh
      release had recovered, whereas the reduction of the D1 facilitatory influence
      persisted. The D1 facilitatory control of ACh neurotransmission thus appears to
      be more sensitive than the D2 inhibitory control to a reduction in DA
      transmission. The new model of DA-ACh interaction resulting from these data casts
      fresh light on the relationship between changes in DA transmission and
      extrapyramidal motor function.

PMID- 1351929
TI  - Glutamate release in experimental ischaemia of the retina: an approach using
      microdialysis.
AB  - A rabbit eye model of neural ischaemia is described that uses an increased
      pressure in the anterior eye chamber to block the capillary supply to the retina.
      A microdialysis probe placed very close to the retinal surface was used to
      monitor release of amino acids during ischaemia. A large (two- to threefold)
      increase in the release of glutamate and O-phosphoserine (twofold), but not of
      six other amino acids monitored, occurred during initial ischaemia. During
      reperfusion after release of intraocular pressure, much larger (five- to 10-fold)
      increases in the release of these amino acids were observed. Parallel ischaemic
      retinal tissue damage was observed. This damage was prevented by ketamine applied
      locally via a superfusion needle, suggesting that glutamate released during
      ischaemia, and particularly during reperfusion, was responsible for cell death.

PMID- 1351930
TI  - Activation of metabotropic glutamate receptors in the hippocampus increases
      cyclic AMP accumulation.
AB  - The selective metabotropic glutamate receptor agonist trans-1-aminocyclopentane
      1,3-dicarboxylic acid (trans-ACPD) stimulates phosphoinositide hydrolysis and
      elicits several physiological responses in rat hippocampal slices. However,
      recent studies suggest that the physiological effects of trans-ACPD in the
      hippocampus are mediated by activation of a receptor that is distinct from the
      phosphoinositide hydrolysis-linked receptor. Previous experiments indicate that
      cyclic AMP mimics many of the physiological effects of trans-ACPD in hippocampal
      slices. Furthermore, recent cloning and biochemistry experiments indicate that
      multiple metabotropic glutamate receptor subtypes exist, some of which are
      coupled to yet unidentified effector systems. Thus, we performed a series of
      experiments to test the hypothesis that ACPD increases cyclic AMP levels in
      hippocampal slices. We report that 1S,3R- and 1S,3S-ACPD (but not 1R,3S-ACPD)
      induce a concentration-dependent increase in cyclic AMP accumulation in
      hippocampal slices. This effect was blocked by the metabotropic glutamate
      receptor antagonist L-2-amino-3-phosphonoproprionic acid but not by selective
      antagonists of ionotropic glutamate receptors. Furthermore, our results suggest
      that 1S,3R-ACPD-stimulated increases in cyclic AMP accumulation are not secondary
      to increases in cell firing or to activation of phosphoinositide hydrolysis.

PMID- 1351931
TI  - Participation of prostaglandin E2 in dopamine D2 receptor-dependent potentiation
      of arachidonic acid release.
AB  - Stimulation of dopamine D2 receptors potentiates Ca2+ ionophore- or ATP-induced
      arachidonic acid (AA) release in D2 receptor cDNA-transfected Chinese hamster
      ovary (CHO) cells [CHO(D2)]. By using a combination of chromatographic,
      biochemical, and radioimmunochemical techniques, we show here that prostaglandin
      (PG) E2 is a major product of AA metabolism in CHO(D2) cells stimulated with the
      Ca2+ ionophore A23187. Formation of this PG was markedly increased by the
      concomitant application of quinpirole, a D2 receptor agonist. In addition, PGE2
      enhanced D2-dependent amplification of AA release, either when it was added (EC50
      = 100 nM) or when it was produced endogenously, as shown by experiments carried
      out with the cyclooxygenase inhibitor indomethacin. The results suggest that PGE2
      may participate in D2 receptor-mediated potentiation of AA release in CHO(D2)
      cells. They also support a functional role for this PG in the modulation of
      dopaminergic transmission in areas of the CNS, such as amygdala and hypothalamus,
      where high levels of both PGE2 and dopamine D2 receptors are found.

PMID- 1351932
TI  - Dopamine efflux from striatum after chronic nicotine: evidence for autoreceptor
      desensitization.
AB  - We examined the effect of chronic nicotine treatment on dopaminergic activity by
      measuring the effects of D1 and D2 dopamine (DA) receptor agonists and
      antagonists on tritium release from mouse striatum preloaded with [3H]DA. The
      radioactivity released during superfusion was separated on alumina columns and
      the distribution and efflux of [3H]DA and its main 3H-labeled metabolites were
      quantified. After preloading by incubation with [3H]DA, the electrical
      stimulation-evoked tritium overflow was higher in striatum prepared from nicotine
      treated mice, whereas in vitro addition of nicotine caused a similar increase in
      tritium release from striatum of untreated and chronic nicotine-treated mice. The
      overflow of [3H]DA and its 3H-metabolites exhibited similar distribution patterns
      in [3H]DA-preloaded striatum dissected from untreated and chronic nicotine
      pretreated mice, indicating that repeated injections with nicotine did not alter
      the metabolism of [3H]DA taken up by the tissue. (-)-Quinpirole, a selective
      agonist for D2 DA receptors, and apomorphine, a nonselective D1/D2 agonist,
      inhibited the electrical stimulation-induced tritium efflux from striatum of
      untreated mice, whereas (+/-)-sulpiride, a D2 DA receptor antagonist, enhanced
      the evoked release of tritium. These changes in tritium efflux effected by (-)
      quinpirole and (+/-)-sulpiride reflected changes in [3H]DA release and not in DA
      metabolism, as shown by separation of the released radioactivity on alumina
      columns. The D1 receptor agonist (+/-)-SKF-38393 did not affect the tritium
      overflow, whereas the D1 receptor antagonist (+)-SCH-23390 exerted a stimulatory
      action but only at a high concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1351933
TI  - Glutamate, of the endogenous primary alpha-amino acids, is specifically released
      from hair cells by elevated extracellular potassium.
AB  - A hair cell (octavolateralis mechanoreceptor cell) sheet preparation from the
      trout saccular macula was superfused with bicarbonate-based physiological saline.
      Among the primary amine-containing compounds resolved by cation-exchange HPLC,
      glutamate alone was released in a statistically significant manner with elevation
      of extracellular [K+] from 3.5 to 14 mM in the presence of 1.8 mM calcium.
      Release of glutamate averaged 10.9 +/- 2.5 pmol (mean +/- SEM) over a 10-min
      period for a hair cell sheet preparation representing 20 micrograms of cell
      protein. No potassium-evoked release of glutamate was observed in 0 mM calcium/10
      mM magnesium saline, suggesting calcium dependency. Because the sheet
      preparation, by the method of its isolation, contained only the hair cell as the
      intact cell type, release of glutamate, induced by relatively small increases in
      extracellular potassium, can be attributed directly to the receptor cell. The
      specific release of glutamate and its block by magnesium are consistent with the
      hypothesis that glutamate is one neurotransmitter/neuromodulator mediating
      receptoneural transmission in the octavolateralis periphery.

PMID- 1351935
TI  - Synaptic basis for developmental plasticity in a birdsong nucleus.
AB  - The development and adult production of birdsong are subserved by specialized
      brain nuclei, including the robust nucleus of the archistriatum (RA), and its
      afferents originating in the caudal nucleus of the ventral hyperstriatum (HVc)
      and the lateral portion of the magnocellular nucleus of the anterior neostriatum
      (L-MAN). An in vitro brain slice preparation was used to characterize the
      electrophysiological properties of L-MAN and HVc axonal synapses within RA and to
      examine how these synaptic connections change during the course of song
      development. Electrical stimulation of L-MAN and not HVc fibers evoked excitatory
      synaptic potentials from virtually all RA neurons in brain slices prepared from
      male and female zebra finches less than 25 d of age. These "L-MAN" EPSPs were
      blocked substantially by the NMDA receptor antagonist D(-)-2-amino-5
      phosphonopentanoic acid (D-APV; 50-100 microM) and by hyperpolarization of the
      postsynaptic membrane. In contrast, when slices were prepared from male finches
      greater than 35 d of age, electrical stimulation of the L-MAN and the HVc fiber
      tracts evoked synaptic responses from over 70% of RA neurons. Although the L-MAN
      EPSPs resembled those seen in RA before day 25, the "HVc" EPSPs were relatively
      insensitive to D-APV, but almost completely abolished by 6-cyano-7
      nitroquinoxaline-2,3-dione, a non-NMDA glutamate receptor antagonist. These
      experiments indicate that L-MAN and HVc axons make pharmacologically distinct
      synapses on the same RA neurons, and that these synapses first form at different
      stages during development.

PMID- 1351934
TI  - GABA-mediated positive autofeedback loop controls horizontal cell kinetics in
      tiger salamander retina.
AB  - Horizontal cells (HCs) appear to release, and also to be sensitive to, GABA. The
      external GABA concentration is increased with depolarization of the HC membrane
      via an electrogenic GABA transporter. This extracellular GABA opens a GABAA-gated
      Cl- channel in the HC membrane. Since the equilibrium potential for Cl- (ECl) is
      near -20 mV, GABA released by the HC further depolarizes the HC. The GABA
      transporter and the GABAA receptor thus constitute a positive feedback loop in
      the HC membrane. This loop can slow down the kinetics of the light responses in
      HCs. GABA released via the GABA transporter can affect the GABAA receptor,
      probably because diffusion from the extracellular space is normally restricted by
      the intact retinal structure. We therefore used retinal slices rather than
      isolated HCs to maintain that structure. To measure single-cell currents in the
      slice, HCs were electrically uncoupled by including cAMP in the patch pipette.
      Under these conditions, bath application of GABA elicited two currents: (1) a
      picrotoxin-blocked current reversing near ECl, probably mediated by GABAA
      receptors, and (2) a picrotoxin-insensitive current similar to that elicited by
      cis-4-hydroxynipecotic acid (NIP) shown in other preparations to act at the GABA
      transporter. Under physiological conditions, the HC membrane potential is
      controlled by two major conductances, the GABAA-gated Cl- conductance described
      above, and the glutamate-gated conductance modulated by photoreceptor input. A
      bright light flash eliminates the glutamate-gated conductance, leaving only the
      GABA-gated Cl- conductance to control the membrane. With the Cl- conductance a
      significant fraction of the overall membrane conductance the GABAergic positive
      feedback loop can decrease the response kinetics. We increased the ambient
      extracellular GABA concentration by adding 50 microM GABA to the extracellular
      medium. This increased the ambient Cl- conductance, but the transporter still
      modulated Cl- conductance because responses to light stimuli were significantly
      slowed. The slowdown of the HC response could be reversed by interrupting the
      loop in two ways: (1) picrotoxin opened the loop and speeded the responses by
      uncoupling the GABA concentration from control of the membrane conductance, and
      (2) NIP opened the loop by uncoupling the extracellular GABA concentration from
      the Cl- conductance and therefore the membrane potential.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1351936
TI  - Calcium excitability and oscillations in suprachiasmatic nucleus neurons and glia
      in vitro.
AB  - Converging lines of evidence suggest that the hypothalamic suprachiasmatic
      nucleus (SCN) is the site of the endogenous biological clock controlling
      mammalian circadian rhythms. To study the calcium responses of the cellular
      components that make up the clock, computer-controlled digital video and confocal
      scanning laser microscopy were used with the Ca2+ indicator dye fluo-3 to examine
      dispersed SCN cells and SCN explants with repeated sampling over time. Ca2+ plays
      an important second messenger role in a wide variety of cellular mechanisms from
      gene regulation to electrical activity and neurotransmitter release, and may play
      a role in clock function and entrainment. SCN neurons and astrocytes showed an
      intracellular Ca2+ increase in response to glutamate and 5-HT, two major
      neurotransmitters in afferents to the SCN. Astrocytes showed a marked
      heterogeneity in their response to the serial perfusion of different
      transmitters; some responded to both 5-HT and glutamate, some to neither, and
      others to only one or the other. Under constant conditions, most neurons showed
      irregular temporal patterns of Ca2+ transients. Expression of regular neuronal
      oscillations could be blocked by the inhibitory transmitter GABA. Astrocytes, on
      the other hand, showed very regular rhythms of cytoplasmic Ca2+ concentrations
      with periods ranging from 7 to 20 sec. This periodic oscillation could be
      initiated by in vitro application of glutamate, the putative neurotransmitter
      conveying visual input to the SCN critical for clock entrainment. Long-distance
      communication between glial cells, seen as waves of fluorescence moving from cell
      to cell, probably through gap junctions, was induced by glutamate, 5-HT, and ATP.
      These waves increased the period length of cellular Ca2+ rises to 45-70 sec.
      Spontaneously oscillating cells were common in culture medium, serum, or rat
      cerebrospinal fluid, but rare in HEPES buffer. One source for cytoplasmic Ca2+
      increases was an influx of extracellular Ca2+, as seen under depolarizing
      conditions in about 75% of the astroglia studied. All neurotransmitter-induced
      Ca2+ fluxes were not dependent on voltage changes, as Ca2+ oscillations could be
      initiated under both normal and depolarizing conditions. Since neurotransmitters
      could induce a Ca2+ rise in the absence of extracellular Ca2+, the mechanisms of
      ultradian oscillations appear to depend on cycles of intracellular Ca2+ fluxes
      from Ca(2+)-sequestering organelles into the cytoplasm, followed by a subsequent
      Ca2+ reduction. In the adult SCN, fewer astrocytes are found than neurons, yet
      astrocytes frequently surround glutamate-immunoreactive axons in synaptic contact
      with SCN dendrites, isolating neurons from each other while maintaining contact
      with other astrocytes by gap junctions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1351937
TI  - The effect of visual experience on development of NMDA receptor synaptic
      transmission in kitten visual cortex.
AB  - We have studied the effect of dark rearing on the development of excitatory amino
      acid transmission in 6-week-old kittens. In normal kittens, the NMDA component of
      the visual response decreases between 3 and 6 weeks of age for cells located in
      layers IV, V, and VI (Fox et al., 1991). Dark rearing to 6 weeks of age prevents
      this decrease. Subsequent exposure to light allows the decrease to proceed. Ten
      days in the light after 6 weeks in the dark was sufficient to decrease the NMDA
      component of the visual response to the same levels seen in light-reared animals
      of the same age. Comparison of the effect of the non-NMDA antagonist 6-cyano-7
      dinitroquinoxaline-2,3-dione with the NMDA antagonist aminophosphonovalerate
      showed that the changes were due to the relative contributions of NMDA and non
      NMDA receptors to the visual response rather than the overall contribution of
      glutamate receptors. We also studied the receptive field properties of the cells
      in the various groups of kittens. Cells given 4 d in the light after 6 weeks in
      the dark showed increased direction selectivity but little change in response
      firing rate. After 10 d in the light, visual responses did show some recovery
      toward adult values, but neither average firing rates nor the proportion of
      direction-selective cells reached the levels found in normal 6-week-old animals,
      contrary to the suggestion that a short period in the light can reverse the
      effect of dark rearing completely. These results show that the decrease in the
      NMDA component of the visual response seen during normal development of the
      cortex is caused by visual experience. Changes in NMDA receptors and
      developmental events such as geniculocortical afferent segregation and
      acquisition of orientation tuning covary as a function of visual experience
      rather than age, strongly suggesting that NMDA receptors are involved in
      experience-dependent developmental processes.

PMID- 1351938
TI  - Intracellular recordings from neurobiotin-labeled cells in brain slices of the
      rat medial nucleus of the trapezoid body.
AB  - Principal cells in the medial nucleus of the trapezoid body (MNTB) are believed
      to be critical components in the circuit subserving sound localization. These
      cells, located in the superior olivary complex, convert excitatory inputs,
      arriving from the contralateral cochlear nucleus by way of large somatic synapses
      (the calyces of Held), to inhibitory projections onto principal cells in the
      ipsilateral lateral superior olive (LSO). We have characterized a population of
      cells in the rat MNTB using intracellular recording and labeling techniques in a
      brain slice preparation. MNTB principal cells had spherical or ellipsoid somata
      that gave rise to single large-diameter dendrites, which branched extensively and
      often extended beyond the borders of MNTB. Commonly observed axonal projection
      targets included LSO, the superior paraolivary nucleus, and the medial superior
      olive, and occasionally the lateral nucleus of the trapezoid body. The
      projections of individual MNTB cells showed an orderly topography that is
      consistent with the known tonotopic maps of the nuclei. In response to current
      injection, principal cells exhibited several nonlinearities, including
      rectification for depolarizing currents and a "sag" in the membrane potential for
      hyperpolarizing currents. Superthreshold depolarizing currents elicited transient
      firing behavior. Application of the potassium channel blocker 4-aminopyridine
      reduced or eliminated the rectification in the current-voltage relationships and
      caused depolarizing currents to elicit repetitive firing. Stimulation of afferent
      inputs elicited short-latency spikes, presumably driven by calyceal synaptic
      inputs; long-latency, presumably polysynaptic, EPSPs; and short- and long-latency
      IPSPs. The duration of synaptic events was strongly dependent on membrane
      potential, and this effect was probably due to the intrinsic membrane properties
      of the cell. In all cases tested, EPSPs were blocked by CNQX or DNQX, and IPSPs
      were blocked by strychnine. Two injected non-principal cells differed from
      principal cells in their morphologies and physiological characteristics.

PMID- 1351939
TI  - Emission tomography for assessment of diffuse alcoholic liver disease.
AB  - A method of quantitative liver tomoscintigraphy (SPECT) was compared for accuracy
      with planar scintigraphy (PS) in a group of patients with diffuse alcoholic liver
      disease. SPECT sensitivity was also compared with that of transmission computed
      tomography (CT), US, aminopyrine breath test (ABT) and liver chemistries (LC).
      One hundred and fourteen alcoholic patients with proven liver disease and 17
      patients free of liver disease were included. Seven quantitative scintigraphic
      features and a score, including all criteria were considered. With a specificity
      of 95%, the sensitivity was 79% in steatosis and 97% in cirrhosis. SPECT showed a
      better sensitivity than PS (SPECT 89%, PS 66%), especially in patients with
      steatosis. In the same subsets of patients, SPECT sensitivity also compared
      favorably with that of transmission CT (SPECT 92%, CT 65%), ultrasonography
      (SPECT 88%, US 53%) and ABT (SPECT 90%, ABT 63%).

PMID- 1351942
TI  - Lack of deletion of complement C4 and steroid 21-hydroxylase genes in Japanese
      patients with primary Sjogren's syndrome.
AB  - A null allele at C4A (C4AQO) is associated with primary Sjogren's syndrome (SS)
      in Japanese. Since a deletion of the C4A and CyP21A genes is reported to account
      for C4AQO in patients with systemic lupus erythematosus (SLE) in Caucasians, we
      studied the restriction fragment length polymorphism (RFLP) of genomic DNA to
      determine whether similar deletions of the C4A and CyP21A genes occur in Japanese
      patients with SS. Patients with C4AQO did not show the extensive deletion of C4A
      and CyP21A, which would be recognized by the appearance of 8.5 kb/HindIII and 6.4
      kb/TaqI fragments hybridizing with a C4 probe. It is yet to be shown whether the
      lack of expression of C4A genes in Japanese patients with primary SS is due to
      point mutations, or to small deletions or insertions that were not detected by
      the RFLP approach.

PMID- 1351943
TI  - An acute remission of Reiter's syndrome in male patients treated with
      bromocriptine.
AB  - We describe 4 male patients with Reiter's syndrome treated with bromocriptine.
      All 4 had infectious gastroenteritis and chronic Reiter's syndrome with arthritis
      and enthesopathy that persisted despite treatment in 3 with antiinflammatory
      drugs and 1 with sulfasalazine for long periods. In all patients treatment was
      cancelled 8 days before bromocriptine treatment. In 2 patients a dramatic
      improvement was observed 24 h after 2.5 mg/day of bromocriptine. Two patients
      improved after 4 days of bromocriptine treatment (5 mg/day). All 4 patients
      remained asymptomatic for at least 4 months of bromocriptine treatment.
      Bromocriptine may be useful for treating male patients with Reiter's syndrome.

PMID- 1351941
TI  - Pruritus: a practical approach.
AB  - Pruritus is usually caused by a primary disorder of the skin, but can also be
      caused by a systemic disease (Table 1). Some dermatologic conditions that cause
      pruritus can be inconspicuous or nonspecific (Table 2), while others are usually
      apparent on physical examination (Table 3). Classification of pruritus as
      localized (Fig. 1) vs. generalized (Fig. 3) can be helpful in arriving at a
      correct diagnosis. The history and physical examination are the most important
      diagnostic tools, though laboratory testing for systemic disease may be
      necessary. In refractory cases, one should consider occult systemic disease (such
      as malignancy), psychiatric disease (especially depression), and HIV infection.
      Subsequent referral to a dermatologist may be indicted. When treatment of the
      underlying cause of pruritus is not possible, antihistamines and topical agents
      (menthol, phenol, and/or pramoxine) can be helpful.

PMID- 1351944
TI  - Increased expression of CD11b (Mo1) on peripheral blood monocytes of patients
      with rheumatoid arthritis.

PMID- 1351940
TI  - Optimal management strategies for HIV-infected patients who present with cough or
      dyspnea: a cost-effective analysis.
AB  - OBJECTIVE: To determine the effectiveness and costs of alternative management
      strategies for patients infected with the human immunodeficiency virus (HIV) who
      present with pulmonary symptoms. DESIGN: Decision analysis comparing initial
      testing (arterial blood gas analysis, induced sputum analysis, or bronchoscopy
      with bronchoalveolar lavage) with empiric antibiotics (trimethoprim
      sulfamethoxazole or erythromycin). Subsequent steps in management are detailed
      based on the results of initial management. Patients were stratified by initial
      CD4 lymphocyte count (less than 200/mm3, 200-500/mm3, or greater than 500/mm3)
      and results of chest radiography. SETTING: Hypothetical. MEASUREMENTS AND MAIN
      RESULTS: The estimated levels of effectiveness among strategies were relatively
      similar, but costs varied markedly. If potentially reasonable strategies are
      defined as those that have incremental cost-effectiveness ratios below $50,000
      per quality-adjusted life year (QALY), the recommended strategies would be: for
      patients at highest risk for Pneumocystis carinii pneumonia (PCP), with a
      probability of PCP above 30% (CD4 less than 200/mm3 and abnormal chest radiograph
      or prior history of PCP), begin with induced sputum analysis ($34,174/QALY); for
      intermediate-risk patients, with a probability of PCP between 6% and 30% (CD4
      less than 200/mm3, regardless of chest radiograph; or CD4 200-500/mm3, regardless
      of chest radiograph findings), begin with arterial blood gas analysis ($4,593 to
      $8,310/QALY); for low-risk patients, with a probability of PCP below 6% (CD4
      greater than 500/mm3, regardless of chest radiograph findings), begin with one
      week of erythromycin, followed by induced sputum examination if symptoms persist
      ($675 to $3,306/QALY). For highest-risk patients, if empiric trimethoprim
      sulfamethoxazole was considered entirely to be outpatient therapy, it was
      preferred management if the probability of PCP was above 38%. CONCLUSIONS: The
      authors conclude that preferred management strategies are determined more by
      differences in costs than by differences in levels of effectiveness, and that
      they vary depending on the probability of PCP in definable patient subgroups.

PMID- 1351945
TI  - Chemistry and anti-HIV properties of 2'-fluoro-2',3'
      dideoxyarabinofuranosylpyrimidines.
AB  - The synthesis, chemistry, biochemistry, and anti-HIV activity of a series of 1
      (2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)pyrimidines have been studied in
      an attempt to find useful anti-AIDS drugs. Synthesis is carried out via a 2,3
      dideoxyribose intermediate which facilitates the preparation of analogues by
      removing the sugar 3'-hydroxyl group prior to, rather than after, condensation
      with a uracil or cytosine aglycon. The 2'-F-dd-uridine analogues 7a-d (with H, F,
      Cl, and CH3 substitution in the 5-position) as well as the 4-deoxy compound (12b)
      are nonprotective to ATH8 or CEM cells infected with HIV-1. In the corresponding
      cytidine series, the 5-chloro analogue (11) is inactive. However, 2'-fluoro-2',3'
      dideoxyarabinosylcytosine, 10a, and its 5-fluoro analogue, 10b, are both active.
      While neither compounds is a potent as ddC or 5-F-ddC (2b), 10b gives complete
      protection against the cytopathic effects of HIV in both host cell lines. 2'
      Fluoro substitution confers increased chemical and enzymatic stability on
      dideoxynucleosides. Even though dideoxy pyrimidine nucleosides are inherently
      more stable than the corresponding purine analogues toward acid-catalyzed
      cleavage of the glycosidic bond, 2'-fluoro substitution (10a) still increases
      stabilization relative to ddC (2b). No detectable deamination by partially
      purified cytidine deaminase is observed with the 2'-fluoro compounds 10a, 10b, or
      11 under conditions which rapidly deaminate cytidine. A small amount of 2'-F-dd
      ara-U (7a) is formed from 10a in monkey plasma after greater than 24 h of
      exposure. The octanol-water partition coefficients for the dideoxynucleosides in
      this study indicate their hydrophilic character, with log P values varying from 
      0.28 to -1.18.

PMID- 1351946
TI  - The lipoprotein lipase Gly188----Glu mutation in South Africans of Indian
      descent: evidence suggesting common origins and an increased frequency.
AB  - Lipoprotein lipase (LPL) plays a crucial role in the hydrolysis of the
      triglyceride core of circulating chylomicrons and very low density lipoproteins
      (VLDL) and also has a major effect on the levels and lipid composition of high
      density lipoproteins (HDL). LPL deficiency is inherited as an autosomal recessive
      trait and most commonly presents with chylomicronaemia, abdominal pain, and
      eruptive xanthomata. We have previously described a mutation in exon 5 of the LPL
      gene which results in a substitution of glutamic acid for glycine at amino acid
      188. We have now assessed 16 South African LPL deficient patients from nine
      separate kindreds for this mutation. Nine of these probands were homozygous for
      the mutation and were from four families, all of Indian descent. The ancestors of
      these probands have their origins in villages close to Bombay, India, which
      suggests a common ancestral mutation for the four Indian kindreds, particularly
      as the mutant allele in each family carried the identical restriction fragment
      length polymorphism (RFLP) haplotype. The presence of at least nine affected
      subjects in this small community around Cape Town is evidence for a higher than
      expected gene frequency for LPL deficiency in this population.

PMID- 1351947
TI  - Multiple mutation in an extended Duchenne muscular dystrophy family.
AB  - We have investigated an extended pedigree with three cousins affected by Duchenne
      muscular dystrophy with apparent transmission through the male line. However,
      molecular studies have shown that one boy has a de novo duplication, another has
      a deletion, and the molecular mutation has yet to be defined in the third boy.
      All three X chromosomes in the affected boys appear to have a different origin.
      We speculate on the mechanisms by which the Duchenne locus may be particularly
      prone to mutation in this family and the possible involvement of transposons is
      discussed. Whatever the mechanism involved, the occurrence of three different
      mutations in one pedigree is a rare event.

PMID- 1351948
TI  - Understanding chemical dependence.

PMID- 1351949
TI  - Preliminary X-ray crystallographic analysis of intercellular adhesion molecule-1.
AB  - Crystals of the two amino-terminal domains of intercellular adhesion molecule-1,
      the receptor for the major group of human rhinovirus serotypes, diffract to 3.0 A
      resolution. The crystals are trigonal in space group P3(1)21 or P3(2)21 with cell
      dimensions of a = b = 55.7 A, c = 166.3 A, with probably six molecules per unit
      cell.

PMID- 1351950
TI  - From adenylate cyclase to guanylate cyclase. Mutational analysis of a change in
      substrate specificity.
AB  - Adenylate and guanylate cyclases, having different but related substrates, are a
      paradigm for the study of substrate discrimination. A prokaryotic adenylate
      cyclase gene, phylogenetically related to eukaryotic counterparts, was screened
      for mutants remodelling the enzyme's specificity. In a first step, a mutant was
      selected displaying a significant level of guanylate cyclase activity. This was
      due to a point mutation destroying most of the adenylate cyclase activity. A
      second selection step restored most of the original activity. This resulted from
      an additional mutation in the same region, thus permitting the first
      identification of a functional domain in adenylate and guanylate cyclases.

PMID- 1351951
TI  - Cholinergic and opioid mediation of traumatic brain injury.
AB  - There is considerable evidence for the involvement of cholinergic and opioid
      systems in the pathophysiological responses associated with traumatic brain
      injury (TBI). To some extent, interest in this area has been eclipsed by a strong
      focus on, and rapid progress in, studies of the role of excitatory amino acids in
      TBI. We present evidence that both cholinergic and opioid systems are important
      modulators of the pathophysiological response to TBI, potentially equally as
      important as excitatory amino acids. There is a relatively large body of
      experimental data documenting the involvement of these systems in TBI that has
      yielded important principles with general significance for laboratory studies of
      the neuropharmacology of TBI. In fact, the first demonstration of excitotoxic
      mechanisms of TBI involved studies of the role of acetylcholine in experimental
      TBI. There also are clinical data suggesting that modulation of opioid and
      cholinergic systems could benefit patients.

PMID- 1351952
TI  - GABA- and glutamate-activated currents in glial cells of the mouse corpus
      callosum slice.
AB  - Whole-cell transmitter-activated currents were recorded with the patch-clamp
      technique from glial cells in thin frontal brain slices of the corpus callosum.
      In slices from 6- to 8-day-old mice, glioblasts were predominantly found, while
      oligodendrocytes were predominant in slices from 10- to 13-day-old mice. These
      developmental stages could be readily distinguished by their K+ channel pattern
      and their morphology and ultrastructural features. Both cell types expressed GABA
      and glutamate receptors in this in situ preparation. GABA responses showed
      similarities to those described for GABAA receptors, i.e., they were mimicked by
      muscimol, blocked by bicuculline, and enhanced by pentobarbital. Glutamate
      responses showed similarities to those of the kainate/quisqualate receptor
      subtype. The amplitude of GABA-activated currents recorded in oligodendrocytes
      was significantly smaller than that from glioblasts, while glutamate responses
      did not show marked differences in either cell type.

PMID- 1351953
TI  - Detubularization-induced contractile response change of the ileum following
      ileocystoplasty.
AB  - We reported previously that following ileocystoplasty the structure and
      pharmacologic response of the implanted ileum changes towards that of the
      bladder. Specifically, the relaxation response to alpha adrenergic (methoxamine)
      and purinergic (ATP) stimulation reverses to a contractile response one month
      after the ileal segment is surgically made part of the urinary bladder. The
      present study was designed to investigate possible signals for this change and
      also to determine whether bladder responses would mimic the ileum if surgically
      interposed into the ileal stream. Rabbits in group 1 underwent bladder
      interposition into the functioning terminal ileum, rabbits in group 2 underwent
      tubularized ileocystoplasty and rabbits in group 3 underwent detubularized
      ileocystoplasty with urinary diversion. Twelve rabbits survived and were
      available for evaluation; five in group 1, three in group 2 and four in group 3.
      Analysis was done six weeks after surgery. In group 1 animals, the interposed
      bladder showed epithelial changes towards ileum and also a change in its in-vitro
      contractile responses towards that of ileum. In group 2 animals the tubular
      cystoplastic ileum showed minimal functional and morphologic changes. In group 3
      animals, the defunctionalized, detubular cystoplastic ileum showed alpha
      adrenergic and purinergic response changes towards bladder. These results
      indicate that detubularization with interruption in the arrangement of smooth
      muscle fibers as well as the breach in the integrity of neuronal connections is
      likely to be the primary signal for the change in the ileum towards bladder
      induced by cystoplasty. The results can not rule out reinnervation of the
      intestinal segment by bladder nerves. In addition these data demonstrate that the
      pharmacologic response of the bladder changes towards the ileum within six weeks
      after the bladder is surgically made part of the ileum.

PMID- 1351954
TI  - Enhanced expression of "muscle-specific" actin in glomerulonephritis.
AB  - Increased expression of "muscle-specific" actin can be correlated with mesangial
      cell injury and proliferation in the rat. We performed similar
      immunohistochemical studies using two monoclonal antibodies (MoAb) to "muscle
      specific" actins (HHF-35, a MoAb to pan muscle actin and alpha-SM-1, a MoAb to
      alpha-smooth muscle actin) on methyl Carnoy's fixed human renal biopsies which
      demonstrated a wide variety of inflammatory, proliferative, and non-proliferative
      glomerular diseases. Most glomerular diseases were associated with increased
      "smooth-muscle" actin expression. Exceptions almost invariably were disease
      settings without prominent cellular proliferation. As in the rat, there was a
      correlation of induced actin expression with increased glomerular cell
      proliferation, as detected by staining with a MoAb to proliferating cell nuclear
      antigen (PCNA). Double immunolabeling studies with an antibody to the leukocyte
      common antigen showed the great majority of PCNA+ proliferating cells to be
      intrinsic glomerular cells rather than infiltrating leukocytes. These studies
      demonstrate that phenotypic changes of mesangial cells occur in both human and
      experimental glomerulonephritis, and are identifiable in fixed tissue sections.
      These studies also suggest that markers of mesangial cell injury or activation
      and proliferation, such as immunostaining of renal biopsies for "muscle-specific"
      actins, might be useful diagnostic and/or prognostic indicators in proliferative
      or sclerosing glomerular diseases.

PMID- 1351955
TI  - Association of IgM with IgG ANCA in patients presenting with pulmonary
      hemorrhage.
AB  - ANCA are markers for systemic vasculitis such as Wegener's granulomatosis (WG)
      and microscopic polyarteritis (MPA) and are usually of the IgG isotype. However,
      IgM ANCA may rarely occur in isolation, and in these circumstances, we have found
      that they are associated clinically with a syndrome of pulmonary hemorrhage and
      systemic vasculitis. How frequently IgM ANCA may occur in conjunction with IgG
      has not previously been investigated. We report here a study of 24 consecutive
      patients with IgG ANCA-positive systemic vasculitis (14 WG, 10 MPA) in whom we
      determined whether IgM ANCA occurred in association with IgG ANCA, and if so,
      whether this had clinical importance. Eight patients were found to have IgM ANCA
      as well as IgG ANCA, and of these, seven presented with severe pulmonary
      hemorrhage. None of the IgM ANCA-negative patients presented with pulmonary
      hemorrhage. Although the occurrence of pulmonary hemorrhage in ANCA positive
      vasculitis was closely correlated with the presence of IgM ANCA, the antigen
      specificity of these IgM autoantibodies was variable, since both myeloperoxidase
      (4 patients), PR3 (3 patients), and an unknown ANCA antigen (1 patient) were
      found to be targets. We conclude that knowledge of ANCA isotype may have
      important clinical and therapeutic implications for the management of patients
      with systemic vasculitis.

PMID- 1351957
TI  - [Multicenter evaluation of a new local antihistaminic drug (levocabastine)].
AB  - The aim of this prospective, open study was to evaluate the efficacy and
      tolerance of the Levocabastine eye drops in daily practice. 273 patients with
      allergic (rhino)conjunctivitis were treated during 2 weeks. Objective findings
      and subjective assessments made by the patients were analyzed. The global
      efficacy was evaluated by the investigator as good or excellent in 73.8% (eye)
      and 53.6% (nose) of the patients. The results were not age-dependent. The
      tolerance was scored as good or excellent in 89% of the patients. Less than 6% of
      the patients stopped the treatment due to intolerance.

PMID- 1351956
TI  - Renal protective aspects of calcium antagonists. International Workshop.
      Florence, Italy, April 14-16, 1991. Proceedings.

PMID- 1351960
TI  - Fundamental mechanisms of transcription. Keystone Symposia on Molecular and
      Cellular Biology. March 28-April 3, 1992. Abstracts.

PMID- 1351958
TI  - Prevention and Treatment of AIDS. Keystone Symposia on Molecular and Cellular
      Biology. March 27-April 3, 1992. Abstracts.

PMID- 1351959
TI  - Critical research directions in pediatric HIV infection. Keystone Symposia for
      Molecular and Cellular Biology. March 27-31, 1992. Abstracts.

PMID- 1351961
TI  - Advances in understanding neurodegenerative disorders. Keystone Symposia on
      Molecular and Cellular Biology. March 28-April 4, 1992. Abstracts.

PMID- 1351962
TI  - Synapse formation and function: the neuromuscular junction and the central
      nervous system. Keystone Symposia on Molecular and Cellular Biology. March 28
      April 4, 1992. Abstracts.

PMID- 1351963
TI  - Molecular Biology of Human Genetic Disease. Keystone Symposia on Molecular and
      Cellular Biology. April 3-10, 1992. Abstracts.

PMID- 1351964
TI  - Tissue Engineering. Keystone Symposia on Molecular and Cellular Biology. April 3
      10, 1992. Abstracts.

PMID- 1351966
TI  - Crop Improvement via Biotechnology: an International Perspective. Keystone
      Symposia on Molecular and Cellular Biology. April 10-16, 1992. Abstracts.

PMID- 1351965
TI  - Integrins: Cell Adhesion and Transmembrane Communication in Development and
      Disease. Keystone Symposia on Molecular and Cellular Biology. April 3-10, 1992.
      Abstracts.

PMID- 1351967
TI  - Gene Transfer, Replacement and Augmentation. Keystone Symposia on Molecular and
      Cellular Biology. April 3-9, 1992. Abstracts.

PMID- 1351968
TI  - Growth and Differentiation Factors in Vertebrate Development. Keystone Symposia
      on Molecular and Cellular Biology. April 3-10, 1992. Abstracts.

PMID- 1351969
TI  - Beta 2 adrenergic receptors in asthma: a current perspective.
AB  - The role of the beta 2-adrenergic receptor in both the pathogenesis and treatment
      of asthma has been a subject of intense speculation and investigation for 25
      years. The physiological effects of endogenous circulating catecholamines and
      exogenous adrenergic agonists in the lung are mediated by the beta 2-adrenergic
      receptor, which is present on a variety of cell types. Documented effects of beta
      2-adrenergic receptor activation in the human lung include smooth muscle
      relaxation, inhibition of acetylcholine release from cholinergic nerve terminals,
      stimulation of serous and mucous cell secretion, increases in ciliary beat
      frequency, promotion of water movement into the airway lumen by stimulation of
      ion secretion across the apical membrane of epithelial cells, increase in
      bronchial blood flow, reduction in venular permeability, and inhibition of
      mediator release from some, but not all, inflammatory cells. Beta 2-Adrenergic
      receptors are present in normal or increased numbers on asthmatic airway smooth
      muscle but are uncoupled in severe asthma, leading to functional
      hyporesponsiveness, probably due to the effects of inflammatory mediators. There
      is also evidence for dysfunction of beta 2-adrenergic receptors on circulating
      inflammatory cells following mediator release. However, dysfunction of the
      receptors on airway smooth muscle and inflammatory cells is unlikely to be of
      primary importance in the pathogenesis of asthma. There is increasing concern
      that regular beta 2-adrenergic receptor agonist use in the therapy of asthma is
      deleterious. Although a number of theories have been advanced to explain such an
      effect, none is well established and further research is urgently required.

PMID- 1351970
TI  - Formoterol, fenoterol, and salbutamol as partial agonists for relaxation of
      maximally contracted guinea pig tracheae: comparison of relaxation with receptor
      binding.
AB  - In severe asthma attacks beta 2-sympathomimetics lose part of their therapeutic
      efficiency. To elucidate this loss of efficiency in an experimental model we
      compared the relaxant potency of salbutamol (SAL), fenoterol (FEN), formoterol
      (FOR), and (-)-isoprenaline (ISO) in guinea pig tracheae partially and maximally
      precontracted by 0.1 and 60 mumol/L carbachol, respectively. In partially
      precontracted tracheae the beta 2-sympathomimetics exerted maximum relaxation in
      comparison with ISO and low EC50S (nmol/L) for relaxation (SAL, 20; FEN, 5.6;
      FOR, 0.28; and ISO, 2.5). In maximally precontracted tracheae, however, the beta
      2-sympathomimetics were only partial agonists for relaxation with reduced
      intrinsic activities (%) in comparison to ISO (SAL, 59%; FEN, 61%; FOR, 76%) and
      significantly increased EC50S (nmol/L) for relaxation (SAL, 130; FEN, 57; FOR,
      3.0; ISO, 37). To investigate if the high relaxant potency of FOR is correlated
      with a higher binding affinity and/or a higher intrinsic activity for adenylate
      cyclase stimulation than for FEN and SAL, we performed experiments in receptor
      membranes from guinea pig lung. Binding competition of SAL, FEN, and FOR with
      [3H]ICI 118,551 for lung beta 2-adrenoceptors yielded dissociation constants (KD)
      of 320 (SAL), 120 (FEN), and 7.6 (FOR) nmol/L, which exhibited the same ranking
      as EC50S for relaxation. Concentrations of SAL, FEN, and FOR equivalent to 100 KD
      of the respective dissociation constants stimulated beta 2-adrenoceptor-coupled
      adenylate cyclase with different intrinsic activities (%) incomparison to ISO
      (SAL, 61%; FEN, 63%; FOR, 89%) matching intrinsic activities for relaxation. From
      these experiments it may be concluded that FOR might improve drug therapy of
      severe asthma not only due to its long mode of action discovered in clinical
      studies but also due to its high intrinsic activity and receptor affinity.

PMID- 1351971
TI  - Relationship between catalase activity, life span and some parameters associated
      with antioxidant defenses in Drosophila melanogaster.
AB  - This study was conducted on Drosophila melanogaster mutants with different levels
      of catalase activity in order to assess the role of antioxidant defenses in the
      aging process. We present here the analysis of two mutant strains: the
      catn1/catn4 heterozygote which exhibits no detectable catalase activity and the
      catn2 homozygote which exhibits approximately 14% that of the parent reference
      strain. Since insects lack glutathione peroxidase activity, catalase activity
      provides the sole enzymatic mechanism for the removal of H2O2. Average and
      maximum life spans of flies were unaffected by the absence or low levels of
      catalase activity. The mutants however exhibited adaptive responses in their
      metabolic rate or glutathione content. The metabolic rate of flies was
      significantly lowered in the null mutants. Glutathione concentration tended to
      increase in flies with the hypomorphic catalase allele (exhibiting 14% of the
      normal catalase activity). Gamma-glutamylcysteine synthetase activity was
      significantly higher in the null flies. Activities of superoxide dismutase and
      glutathione reductase were unaffected. Results of this study indicate that 14% of
      the normal level of catalase activity allows flies to achieve both a normal life
      span and a normal metabolic potential. Small decreases in certain antioxidant
      defenses, frequently observed during aging, may be functionally not very
      consequential.

PMID- 1351973
TI  - The Lancet's statistical review process: areas for improvement by authors.
AB  - The Lancet now incorporates statistical review of submitted papers which remain
      candidates for publication after conventional review. We summarise here
      criticisms noted by the statistical reviewers for 191 such papers received
      between November, 1990, and June, 1991. Only 54% of papers were deemed acceptable
      or acceptable after revision; the others were either recommended for rejection
      (14%) or for more substantial revision and re-review (32%). Descriptions of
      methods and of results were found inadequate in about half of the papers; about
      one-quarter of papers had inadequate abstracts and conclusions. Major errors of
      inference were made in 48 papers and went hand in hand with major criticisms of
      analysis or design in those papers. The natural focus of statistical review is
      whether conclusions drawn are justified by study design and statistical analysis.
      In this, there is room for improvement by authors.

PMID- 1351974
TI  - The new politics of AIDS.

PMID- 1351972
TI  - Anti-inflammatory drugs in the treatment of allergic disease.
AB  - The treatment of asthma is undergoing significant change with an emphasis on anti
      inflammatory therapy. While glucocorticoids are the most potent anti-inflammatory
      agent, certain patients fail to respond. These patients may be candidates for
      alternative anti-inflammatory therapy, such as troleandomycin, methotrexate,
      gold, hydroxychloroquine, or dapsone. In addition, the application of
      immunomodulator therapy, such as intravenous gamma globulin or cyclosporine, may
      be useful.

PMID- 1351975
TI  - Refusal of treatment by 16-year-old.

PMID- 1351976
TI  - HPV in cervical smears.

PMID- 1351977
TI  - Population movements and cholera spread in Cordillera Province, Santa Cruz
      Department, Bolivia.

PMID- 1351978
TI  - Predisposition and ascaris infection.

PMID- 1351979
TI  - Artificial breeding grounds for mosquito control.

PMID- 1351980
TI  - Corynebacterium pseudodiphtheriticum pulmonary infection in AIDS patients.

PMID- 1351981
TI  - Parvovirus-B19-related pancytopenia in children with HIV infection.

PMID- 1351983
TI  - Cryopreservation of embryos and pregnancy rates after IVF.

PMID- 1351984
TI  - Diagnostic difficulties of HCV serological tests.

PMID- 1351982
TI  - Erbium YAG laser for micromanipulation of oocytes and spermatozoa.

PMID- 1351985
TI  - RIBA-2 band intensity and PCR in HCV infection.

PMID- 1351986
TI  - Antiphospholipid antibodies and recurrent thrombo-occlusive events.

PMID- 1351987
TI  - Fish oil supplementation in pregnancy.

PMID- 1351988
TI  - Medical audit of the investigation of toxoplasmosis associated with pregnancy.

PMID- 1351990
TI  - Chest pain and the oesophagus.

PMID- 1351989
TI  - Aflatoxin biomarkers.

PMID- 1351991
TI  - Abortion.

PMID- 1351992
TI  - Abortion.

PMID- 1351993
TI  - Calcitonin treatment of osteoporosis in Italy.

PMID- 1351994
TI  - Deaths from tobacco.

PMID- 1351995
TI  - Serological evidence for congenital transmission of human herpesvirus 6.

PMID- 1351996
TI  - Breast screening.

PMID- 1351997
TI  - X-ray mammography and breast compression.

PMID- 1351998
TI  - LDL oxidation and coronary atherosclerosis.

PMID- 1351999
TI  - LDL oxidation and coronary atherosclerosis.

PMID- 1352000
TI  - LDL oxidation and coronary atherosclerosis.

PMID- 1352001
TI  - Recurrent Kikuchi's disease.

PMID- 1352002
TI  - Intravenous magnesium loading in chronic fatigue syndrome.

PMID- 1352004
TI  - Dopamine, tremor, and Parkinson's disease.

PMID- 1352003
TI  - Lack of pyramidal tract signs in Parkinson's disease.

PMID- 1352005
TI  - Argyria from excessive use of topical silver sulphadiazine.

PMID- 1352006
TI  - Diclofenac-induced pseudomembranous colitis.

PMID- 1352007
TI  - Peripheral neuropathy associated with fluoroquinolones.

PMID- 1352008
TI  - Cholesterol inhibition, cancer, and coronary heart disease.

PMID- 1352009
TI  - Cholesterol inhibition, cancer, and coronary heart disease.

PMID- 1352010
TI  - Cholesterol inhibition, cancer, and coronary heart disease.

PMID- 1352011
TI  - Prevention of excess neonatal morbidity associated with group B streptococci by
      vaginal chlorhexidine disinfection during labour. The Swedish Chlorhexidine Study
      Group.
AB  - Streptococcus agalactiae transmitted to infants from the vagina during birth is
      an important cause of invasive neonatal infection. We have done a prospective,
      randomised, double-blind, placebo-controlled, multi-centre study of chlorhexidine
      prophylaxis to prevent neonatal disease due to vaginal transmission of S
      agalactiae. On arrival in the delivery room, swabs were taken for culture from
      the vaginas of 4483 women who were expecting a full-term single birth. Vaginal
      flushing was then done with either 60 ml chlorhexidine diacetate (2 g/l) (2238
      women) or saline placebo (2245) and this procedure was repeated every 6 h until
      delivery. The rate of admission of babies to special-care neonatal units within
      48 h of delivery was the primary end point. For babies born to placebo-treated
      women, maternal carriage of S agalactiae was associated with a significant
      increase in the rate of admission compared with non-colonised mothers (5.4 vs
      2.4%; RR 2.31, 95% CI 1.39-3.86; p = 0.002). Chlorhexidine reduced the admission
      rate for infants born of carrier mothers to 2.8% (RR 1.95, 95% CI 0.94-4.03), and
      for infants born to all mothers to 2.0% (RR 1.48, 95% CI 1.01-2.16; p = 0.04).
      Maternal S agalactiae colonisation is associated with excess early neonatal
      morbidity, apparently related to aspiration of the organism, that can be reduced
      with chlorhexidine disinfection of the vagina during labour.

PMID- 1352012
TI  - Physiological effects of emotion: assessment via hypnosis.
AB  - Assessment of the physiological effects of physical and emotional stress has been
      hampered by a lack of suitable laboratory techniques. Since hypnosis can be used
      safely to induce specific emotional states of considerable intensity, we studied
      the effect on distal colonic motility of three hypnotically induced emotions
      (excitement, anger, and happiness) in 18 patients aged 20-48 years with irritable
      bowel syndrome. Colonic motility index was reduced by hypnosis on its own (mean
      change 19.1; 95% CI 0.8, 37.3; p less than 0.05) and this change was accompanied
      by decreases in both pulse (12; 8, 15) and respiration (6; 4, 8) rates (p less
      than 0.001 for both). Anger and excitement increased the colonic motility index
      (50.8; 29.4, 72.2; and 30.4; 8.9, 51.9, respectively; p less than 0.01 for both),
      pulse rate (26; 22, 30; and 28; 24, 32; p less than 0.001 for both), and
      respiration rate (14; 12, 16; and 12; 10, 14; p less than 0.001 for both).
      Happiness further reduced colonic motility although not significantly from that
      observed during hypnosis alone. Changes in motility were mainly due to
      alterations in rate than in amplitude of contractions. Our results indicate that
      hypnosis may help in the investigation of the effects of emotion on physiological
      functions; this approach could be useful outside the gastrointestinal system. Our
      observation that hypnosis strikingly reduces fasting colonic motility may partly
      explain the beneficial effects of this form of therapy in functional bowel
      disorders.

PMID- 1352013
TI  - Growth of human umbilical-cord blood in longterm haemopoietic cultures.
AB  - Cryopreserved human umbilical-cord (HUC) blood is an alternative to bone marrow
      as a source of haemopoietic "stem" cells for HLA-identical transplantation of
      children with leukaemia or Fanconi's anaemia. We have studied the in-vitro growth
      potential of HUC blood in clonogenic assays and in longterm haemopoietic
      cultures. Clonogenic assays showed that HUC blood produced as many haemopoietic
      cell colonies as normal adult bone marrow and a higher proportion of primitive
      cell colonies. In longterm culture on preformed irradiated marrow stroma, both
      progenitor-cell production and lifespan of cultures were significantly greater in
      HUC blood than in normal bone marrow (p = 0.0007). Our findings indicate that the
      quality and quantity of HUC-blood-derived haemopoietic "stem" cells are better
      than those of normal bone marrow. Therefore, single HUC-blood donations are
      probably sufficient for adults requiring transplantation for leukaemia and other
      haemopoietic disorders. Banking of HLA-typed HUC blood to facilitate
      transplantation of patients who lack a family donor should be considered.

PMID- 1352014
TI  - Disseminated "Mycobacterium genavense" infection in patients with AIDS.
AB  - We describe 18 patients with advanced HIV infection, most of whom had a chronic
      illness characterised by fever, diarrhoea, and massive loss of weight. Biopsy and
      necropsy samples revealed abundant acid-fast microorganisms in intestines, liver,
      spleen, lymph nodes, and many other tissues, which did not grow on solid media,
      although limited growth was observed in liquid blood cultures. Using primers
      complementary to bacterial 16S rRNA we amplified DNA sequences from tissue and
      leucocyte extracts and from blood-culture bottles. The sequences obtained were
      unique and suggest that the microorganism is a new member of the genus
      Mycobacterium, for which we propose the name "Mycobacterium genavense".
      Disseminated infection with "M genavense" should be considered in the
      differential diagnosis of HIV-infected patients with extreme immunosuppression,
      wasting, and fever.

PMID- 1352015
TI  - Low cerebrospinal fluid concentration of free gamma-aminobutyric acid in startle
      disease.
AB  - The pathophysiology of startle disease (hyperekplexia) is unknown. Hyperactivity
      of the brainstem reticular formation has been suggested as a cause. We report a
      newborn infant with classic features of startle disease in whom cerebrospinal
      fluid (CSF) concentrations of gamma-aminobutyric acid (GABA) were substantially
      lower than normal during the first weeks of life. She improved greatly on
      clonazepam treatment. We suggest that the signs of this disorder may be due to a
      genetic defect or to delayed maturation resulting in low CSF GABA.

PMID- 1352016
TI  - Detection of Chlamydia trachomatis DNA in joints of reactive arthritis patients
      by polymerase chain reaction.
AB  - In 1986, Chlamydia trachomatis elementary bodies were found by direct
      immunofluorescence (DIF) in synovial-fluid cell deposits and synovial-membrane
      biopsy samples from five of eight patients with sexually acquired reactive
      arthritis (SARA) but in none of eight controls with other types of arthritis.
      Cells from the original slides (stored at 4 degrees C) have now been examined by
      a polymerase chain reaction (PCR) that amplifies DNA for the major outer membrane
      protein of C trachomatis. Chlamydial DNA was found in samples from four DIF
      positive patients, one DIF-negative patient, and one DIF-negative control.
      Overall, there was 80% concordance for DIF and PCR results. This study supports
      our previous finding of chlamydiae in joints in reactive arthritis.

PMID- 1352017
TI  - Steroid anaesthetic agents.

PMID- 1352018
TI  - Pneumococcal vaccination for travel to Spain?

PMID- 1352019
TI  - Reversibility of airflow obstruction: FEV1 vs peak flow.

PMID- 1352020
TI  - Medical schools and NHS reforms: death knell of the Universities Funding Council.

PMID- 1352021
TI  - Diagnosing recurrent suffocation of children.

PMID- 1352022
TI  - Pathophysiology of chronic heart failure.

PMID- 1352023
TI  - Treatment of chronic heart failure.

PMID- 1352024
TI  - Ondansetron + dexamethasone vs metoclopramide + dexamethasone + diphenhydramine
      in prevention of cisplatin-induced emesis. Italian Group For Antiemetic Research.
AB  - Ondansetron, a selective serotonin-receptor antagonist, is an effective
      antiemetic for patients receiving high-dose cisplatin chemotherapy. However, no
      comparison has been made between a combination of a serotonin antagonist and
      dexamethasone, which also has antiemetic properties, with currently available
      antiemetic regimens. 289 consecutive cancer patients receiving cisplatin
      chemotherapy (much greater than 50 mg/m2) were randomised to receive one of the
      following intravenous antiemetic regimens: ondansetron 0.15 mg/kg, before and
      after cisplatin, + dexamethasone 20 mg before cisplatin (treatment A) or
      metoclopramide 3 mg/kg, before and after cisplatin, + dexamethasone +
      diphenhydramine 50 mg before cisplatin (treatment B). From day 2 to day 4, all
      patients received oral metoclopramide and intramuscular dexamethasone. 267
      patients (136 receiving treatment A and 131 treatment (B) were available for
      analysis. Complete protection against emesis was achieved in 107 (78.7%) and 78
      (59.5%) patients, respectively (p less than 0.002). Complete protection was also
      significantly superior for treatment A on day 2 (83.9% vs 68.0%; p less than
      0.006). Complete protection from acute nausea (first 24 h) was achieved in 105
      patients (77.2%) with treatment A and in 86 (65.6%) with treatment B (p less than
      0.051); complete protection from nausea and emesis was achieved in 94 (69.1%)
      patients and 66 (50.4%), respectively (p less than 0.003). Patients receiving
      treatment B noted significantly more sedation than patients receiving treatment A
      (11.8% vs 2.1%; p less than 0.005). Extrapyramidal reactions were present only
      with treatment B (2.7%). Ondansetron + dexamethasone is more effective and better
      tolerated than metoclopramide + dexamethasone + diphenhydramine in the prevention
      of cisplatin-induced nausea and emesis.

PMID- 1352025
TI  - Alpha 1-adrenoceptor blocking properties of spiroxatrine in rat aorta.
AB  - This preliminary study has analyzed the potential ability of the 5-HT1A ligand
      spiroxatrine to interact with vascular alpha 1-adrenoceptors. Norepinephrine and
      the selective alpha 1-adrenoceptor agonist, methoxamine, elicited concentration
      dependent contractions of rat aortic rings. In contrast, (+/-)-spiroxatrine (from
      10(-8) to 3.1X10(-7) M) was devoid of any effect on vascular tone per se, but
      shifted the concentration-response curves of norepinephrine and methoxamine to
      the right in a concentration-dependent manner with pA2 values of 8.48 +/- 0.22
      and 8.93 +/- 0.33, respectively. Endothelium removal did not significantly affect
      the above pA2 values of (+/-)-spiroxatrine. These data, taken in concert, support
      the contention that (+/-)-spiroxatrine displays alpha 1-adrenoceptor blocking
      properties in rat aortic rings.

PMID- 1352026
TI  - Modulation of acute morphine tolerance by corticotropin-releasing factor and
      dynorphin A in the mouse spinal cord.
AB  - Previously, we have demonstrated that intrathecally (i.t.) administered
      corticotropin-releasing factor (CRF) in mice produces stimulus-specific
      antinociception and modulation of morphine-induced antinociception by mechanisms
      involving spinal kappa opioid receptors. Recently, we also have found that CRF
      releases immunoreactive dynorphin A, a putative endogenous kappa opioid receptor
      agonist, from superfused mice spinal cords in vitro. Dynorphin A administered
      intracerebroventricularlly (i.c.v.) to mice has been shown to modulate the
      expression of morphine tolerance. In the present study, the possible modulatory
      effects of i.t. administered CRF as well as dynorphin A on morphine tolerance
      were studied in an acute tolerance model. Subcutaneous administration of 100
      mg/kg of morphine sulfate (MS) to mice caused an acute tolerance to morphine
      induced antinociception. The antinociceptive ED50 of MS was increased from 4.4
      mg/kg (naive mice) to 17.9 mg/kg (4 hours after the injection of 100 mg/kg MS).
      To study the modulatory effects of spinally administered CRF and dynorphin A on
      the expression of morphine tolerance, CRF and dynorphin A were injected i.t. at
      15 min and 5 min, respectively, before testing the tolerant mice by the tail
      flick assay. The antinociceptive ED50 of MS in tolerant mice was decreased to 8.8
      mg/kg and 7.1 mg/kg, respectively, after i.t. administration of CRF (0.1 nmol)
      and dynorphin A (0.2 nmol). In contrast, 0.5 nmol of alpha-helical CRF (9-41), a
      CRF antagonist and 0.4 nmol of norbinaltorphimine, a highly selective kappa
      opioid receptor antagonist, when administered i.t. at 15 min before the tail
      flick test in tolerant mice, increased the antinociceptive ED50 of MS to 56.6
      mg/kg and 88.8 mg/kg, respectively. These data confirmed the modulatory effect of
      dynorphin A on morphine tolerance and suggested that CRF, which releases
      dynorphin A in several central nervous system regions, also plays a modulatory
      role in the expression of morphine tolerance.

PMID- 1352027
TI  - Endocrine and receptor pharmacology of serotonergic anxiolytics, antipsychotics
      and antidepressants.
AB  - Several classes of drugs that modify serotonin (5-HT) neurotransmission are
      either currently used, or are being evaluated for their potential use in the
      treatment of anxiety, schizophrenia, and depression. 5-HT1A agonists are
      considered potential anxiolytics, while some atypical antipsychotics are potent 5
      HT2 antagonists (and also have modest dopamine D2 affinity). Furthermore, there
      is a diverse group of serotonergic drugs that may be effective antidepressants.
      Secretion of ACTH, corticosterone/cortisol, prolactin, renin, oxytocin and
      vasopressin are stimulated by activation of different 5-HT receptor subtypes,
      while other neurotransmitter receptors also influence the secretion of these
      hormones. We compared the receptor binding profiles of 5-HT anxiolytics,
      antipsychotics and antidepressants with their endocrine effects. These
      comparisons could aid in understanding both the therapeutic and side effects of
      these drugs.

PMID- 1352028
TI  - Stress-induced changes in brain Met-enkephalin, Leu-enkephalin and dynorphin
      concentrations.
AB  - Methionine-enkephalin (Met-enkephalin), leucine-enkephalin (Leu-enkephalin) and
      dynorphin A (1-17) (dynorphin A) concentrations in discrete brain areas were
      determined in the mice showing behavioral changes induced by stress using
      radioimmunoassay (RIA). In the present experiment, we used environment-induced
      conditioned suppression of motility and forced swimming-induced immobility. In
      the environment-induced conditioned suppression of motility, Met-enkephalin
      concentration in the striatum and hypothalamus significantly decreased. Leu
      enkephalin concentration in the hypothalamus also decreased. Dynorphin A
      concentration in the striatum decreased, but significantly increased in the
      hypothalamus and pituitary. In the forced swimming-induced immobility, Met
      enkephalin concentration in the striatum significantly decreased. Leu-enkephalin
      concentration in the hypothalamus and pituitary significantly decreased.
      Dynorphin A concentration in the pituitary decreased, but significantly increased
      in the hypothalamus. Our results indicated that the concentrations of Met
      enkephalin, Leu-enkephalin and dynorphin A in the discrete brain areas changed in
      two different stressful situations. These findings suggested that these peptides
      might modulate the behavioral changes induced by stressors.

PMID- 1352029
TI  - Human injuries following jellyfish stings.
AB  - There are approximately 500,000 jellyfish stings every year in the Chesapeake
      Bay. Dr. Burnett describes the mechanism of jellyfish stings, venom components,
      types of reactions, diagnosis, and therapy.

PMID- 1352030
TI  - Interaction of heat-stable enterotoxins with human colonic (T84) cells:
      modulation of the activation of guanylyl cyclase.
AB  - Heat-stable enterotoxins (ST) activate guanylyl cyclase in T84 cells, rapidly and
      specifically. Activation is monitored by cGMP production and occurs at lower
      concentrations of ST than required for eliciting fluid accumulation in suckling
      mice. Atrial natriuretic factor (ANF) neither activates guanylyl cyclase nor
      modulates the response to ST in T84 cells, indicating the absence of receptors
      for ANF on T84 cells. Monitoring the production of cGMP under conditions known to
      alter fluid accumulation in suckling mice is an accurate and quantifiable assay
      of ST activity and its interaction with the receptor. STs produced by Escherichia
      coli, Vibrio cholerae non-01 and Yersinia enterocolitica individually produce
      elevated levels of cGMP in T84 cells, but to differing extents, suggesting that
      this model system can be used to elucidate the different events of ST-receptor
      interactions at the molecular level.

PMID- 1352031
TI  - Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins:
      XXVI. Evolutionary significance of carcinogen-induced embryonic gene activity.
AB  - Besides the major theme of this series of writings--that chemically derepressed
      embryonic genes are fundamental to the mechanisms of carcinogenesis, there appear
      to be other significant aspects to this process. Yeast cells have the ability to
      differentially respond to carcinogens and non-carcinogens by the activation of
      embryonic type genes that are also found in mammals. This strange relationship is
      interpreted here as being due to certain phylogetically conserved genes from
      yeasts existing also in mammals that are used in both organisms for the same
      process. For example, a protooncogene found in yeast cells or embryonic cells
      serves for rapid mitosis. Also yeast mating type genes have high homologies to
      homeotic domains and therefore may be prototype genes of homeotic genes, which
      are embryonic type genes in animals.

PMID- 1352032
TI  - Flumazenil.

PMID- 1352033
TI  - Cationic lipids enhance cellular uptake and activity of phosphorothioate
      antisense oligonucleotides.
AB  - We have investigated the use of a cationic lipid preparation to enhance antisense
      oligonucleotide activity in human umbilical vein endothelial cells. A liposomal
      preparation containing the cationic lipid N-[1-(2,3-dioleyloxy)propyl]-N,N,N
      trimethylammonium chloride (DOTMA) was found to increase by at least 1000-fold
      the potency of an antisense oligonucleotide (ISIS 1570) that hybridizes to the
      AUG translation initiation codon of human intercellular adhesion molecule-1. In
      the presence of 8 microM DOTMA, 6-15-fold more 35S-ISIS 1570 associated with
      cells, at oligonucleotide concentrations from 0.01 to 5 microM, than did in the
      absence of DOTMA. Both 35S-ISIS 1570 association with cells and antisense
      activity were increased as a function of DOTMA concentration and with increasing
      time of incubation with the cationic lipid. Fluorescein-labeled ISIS 1570 was
      used to assess the intracellular distribution of the oligonucleotide in the
      presence and absence of DOTMA. In the absence of DOTMA, the oligonucleotide
      localized to discrete structures in the cytoplasm of the cell, resulting in a
      punctate fluorescence pattern. In the presence of DOTMA, cellular fluorescence
      markedly increased and the oligonucleotide localized within the nucleus, as well
      as to discrete structures in the cytoplasm. Accumulation of the oligonucleotide
      in the nucleus in the presence of DOTMA was time and temperature dependent.
      Nuclear accumulation was inhibited by preincubation of the cells with monensin
      but not chloroquine, NH4Cl, nocodazole, colcemid, or brefeldin A. These data
      demonstrate that cationic lipids increase antisense activity by increasing the
      amount of oligonucleotide associated with cells and altering intracellular
      distribution of the oligonucleotide.

PMID- 1352034
TI  - Lack of apparent receptor reserve at postsynaptic 5-hydroxytryptamine1A receptors
      negatively coupled to adenylyl cyclase activity in rat hippocampal membranes.
AB  - Previous studies have demonstrated the existence of a large receptor reserve for
      agonists at somatodendritic 5-hydroxytryptamine1A (5-HT1A) serotonin receptors in
      the raphe nuclei of the rat. 5-HT1A agonists with anxiolytic properties (e.g.,
      buspirone, gepirone, and ipsapirone) display full intrinsic activity at these
      receptors but are partial agonists at postsynaptic 5-HT1A receptors, which
      suggests that the latter sites may be devoid of a receptor reserve. In the
      present studies, this was directly determined by examining the relationship
      between receptor occupancy and response at postsynaptic 5-HT1A receptors, in rat
      hippocampus, mediating the inhibition of forskolin-stimulated adenylyl cyclase
      activity, using the method of partial irreversible receptor inactivation. Rats
      were treated with vehicle or the irreversible antagonist N-ethoxycarbonyl-2
      ethoxy-1,2-dihydroquinoline (EEDQ), and 24 hr later hippocampi were removed for
      saturation analysis of [3H]8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT)
      binding to 5-HT1A receptors or for adenylyl cyclase assays. EEDQ (1 and 6 mg/kg)
      dose-dependently reduced the maximal number of [3H]8-OH-DPAT binding sites by
      68.5 and 80%, respectively, without altering the Kd. Concentration-response
      curves were generated for inhibition of forskolin-stimulated adenylyl cyclase
      activity by 5-HT and the selective 5-HT1A agonist N,N-dipropyl-5
      carboxamidotryptamine (DP-5-CT). EEDQ treatment dose-dependently reduced the
      maximal inhibitory effect of 5-HT [percentage of inhibition: control, 23.6; EEDQ
      (1 mg/kg), 13.4; EEDQ (6 mg/kg), 8.9], without altering either the slope factor
      (1.01) or the EC50 (96.4 nM). Analogous results were obtained with DP-5-CT
      [percentage of maximal inhibition: control, 24.1; EEDQ (1 mg/kg), 15.2; EEDQ (6
      mg/kg), 10.7), again without changes in slope factor (0.89) or EC50 (9.9 nM).
      Analysis of double-reciprocal plots of equieffective concentrations of agonist,
      followed by calculation of fractional receptor occupancy, revealed a linear
      relationship between receptor occupancy and response for both 5-HT and DP-5-CT
      (i.e., an absence of receptor reserve). The receptor specificity of the effect of
      EEDQ was demonstrated in two ways. First, it was shown that pretreatment of rats
      with the selective 5-HT1A partial agonist BMY 7378 (10 mg/kg) before EEDQ
      afforded substantial protection (about 75%) against loss of the inhibitory effect
      of DP-5-CT on forskolin-stimulated adenylyl cyclase activity. Second, EEDQ did
      not alter the inhibition of forskolin-stimulated adenylyl cyclase activity
      induced by the adenosine A1 receptor agonist phenylisopropyladenosine
      (PIA).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1352035
TI  - Identification of two affinity states of low affinity receptors for Escherichia
      coli heat-stable enterotoxin: correlation of occupation of lower affinity state
      with guanylate cyclase activation.
AB  - Two distinct affinity states of low affinity Escherichia coli heat-stable
      enterotoxin (ST) receptors in rat intestinal membranes, with dissociation
      constants of 0.12 and 2.5 nM, were identified. Kinetic binding studies
      demonstrated biphasic association kinetics, whereas dissociation was unimodal.
      These studies also confirmed that ligand bound to each receptor state in an
      independent bimolecular reaction. In contrast, equilibrium binding studies
      yielded linear Scatchard plots, indicative of a single class of noninteractive
      binding sites, with a Kd = 2.3 nM. Close agreement of the dissociation constants
      determined by kinetic and equilibrium methods suggested that receptors were in
      the lower affinity state at equilibrium. Several models, including binding site
      heterogeneity, cooperativity, and ligand-induced alterations in receptor
      conformation were inconsistent with these observations. Indeed, these data were
      most consistent with a two-step binding process involving a third component.
      Comparison of the ligand dependence of enzyme activation (EC50 = 124 nM) and the
      calculated fractional receptor occupancy of the lower affinity component at 5 min
      (EC50 = 40 nM) demonstrated that occupation of the lower affinity state of low
      affinity ST receptors correlated with guanylate cyclase activation. The close
      correlation between receptor occupation and enzyme activation suggests that there
      are no spare receptors for ST in intestinal membranes. These data resolve the
      previously observed discrepancy between the affinity of receptors for ST and the
      potency of this ligand for activating guanylate cyclase. Receptor affinity state
      alterations may represent a common mechanism for receptor-effector coupling of
      particulate guanylate cyclases.

PMID- 1352036
TI  - Competitive antagonism of glutamate receptor channels by substituted benzazepines
      in cultured cortical neurons.
AB  - Whole-cell recordings from rat cortical neurons in dissociated cell culture were
      used to study the antagonism of glutamate receptors by several lipophilic
      benzazepine analogues of 2,5-dihydro-2,5-dioxo-3-hydroxy-1H-benzazepine (DDHB).
      DDHB and three substituted derivatives, 4-bromo-, 7-methyl-, and 8-methyl-DDHB,
      inhibited the activation of N-methyl-D-aspartate (NMDA) receptors at both the
      NMDA recognition site and the glycine allosteric site. In addition, all four
      compounds blocked the activation of non-NMDA receptors by kainate and L
      glutamate. Antagonism by the four benzazepines was equivalent at holding
      potentials from -80 mV to +50 mV. Both the onset of and recovery from block of
      the agonist-gated currents were complete within seconds. Antagonist affinity was
      calculated from the displacement of steady state concentration-response curves
      for kainate, L-glutamate, glycine, and NMDA, based on the Gaddum-Schild
      relationship (dose ratio = 1 + [antagonist]/KB). The most potent blocker, 8-Me
      DDHB, had an apparent dissociation constant (KB) of 470 nM at the glycine
      allosteric site and 27 microM at the NMDA recognition site. The apparent
      dissociation constant of 8-Me-DDHB for non-NMDA receptors was 6.4 microM when
      kainate was the agonist and 9.6 microM when L-glutamate was the agonist.
      Unsubstituted DDHB showed slightly higher affinity for the NMDA recognition site
      (KB = 16 microM) but was less potent than 8-Me-DDHB at the glycine allosteric
      site and at non-NMDA receptors (KB = 3 and 65 microM, respectively). At all three
      sites, the inhibitory actions of these benzazepine derivatives were consistent
      with a simple competitive mechanism of antagonism. In addition, the antagonist
      potency of the parent compound, DDHB, against kainate, NMDA, and glycine was
      equal to or greater than that of other bicyclic antagonists, including kynurenic
      acid, indole-2-carboxylic acid, and quinoxaline-2,3-dione. Substituted
      benzazepines represent a new class of glutamate receptor antagonists that show
      competitive action, significant potency at multiple sites, and a high degree of
      lipophilicity.

PMID- 1352038
TI  - [Developmental disorders of man. Part 2].
AB  - At the beginning of this century genetics arose out of developmental history
      (Entwicklungsgeschichte) as the science of the causal understanding of
      development. After Spemann's epochal discovery (justifiably rewarded with the
      Nobel Prize in 1935) of the organizer and the beginning of the experimental
      analysis of developmental fields, little or no progress was made until the last
      few years when a virtual revolution occurred in developmental biology. If nothing
      else, this revolution has re-inspired in medicine an enormous respect for
      developmental animal models which are homologous to the human condition in the
      strict sense of the term, both in formal (formalgenetischer) and causal
      (kausalgenetischer) respects. Thus, the earliest stages of development in the
      primary field (during gastrulation) and in the later mosaic of secondary,
      epimorphic fields, represents the harmonically coordinated and epigenetically
      regulated effects of many genes which (with of without imprinting) code for
      cellular adhesion molecules, the peptide regulatory factors, homeobox genes,
      retinoic acid receptors and many other genes. Some of these genes act as
      regulators of DNA transcription, and, until recently no clinically identifiable
      developmental attribute to their function was known in humans. However, just in
      the last few weeks we have witnessed the identification of a gene on 11p13 in
      humans which is a paired box- and homeobox-containing gene as the cause of human
      aniridia, with the identical (homologous) mutation in the mouse Pax-6 gene
      producing the Sey phenotype (small eye).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352039
TI  - Developmental biology. Homing in on the homeobox.

PMID- 1352037
TI  - Peptides from the N-terminus of the atrial natriuretic factor prohormone enhance
      guanylate cyclase activity and increase cyclic GMP levels in a wide variety of
      tissues.
AB  - The 98 amino acid (a.a.) N-terminus of the 126 a.a. atrial natriuretic factor
      (ANF) prohormone contains three peptides consisting of a.a. 1-30 (proANF 1-30),
      a.a. 31-67 (proANF 31-67) and a.a. 79-98 (proANF 79-98) with blood pressure
      lowering, sodium and/or potassium excreting properties similar to atrial
      natriuretic factor (a.a. 99-126, C-terminus of prohormone). ProANF 1-30 and
      proANF 31-67 have separate and distinct receptors from ANF in both vasculature
      and in the kidney to help mediate the above effects. At the cellular level
      proANFs 1-30, 31-67, and 79-98 as well as ANF's effects are mediated by
      enhancement of the guanylate cyclase (EC 4.6.1.2)-cyclic GMP system in
      vasculature and in the kidney. These peptides from the N-terminus of the ANF
      prohormone circulate normally in man and in all animal species tested. The object
      of the present investigation was to determine if these peptides have the ability
      to enhance either guanylate cyclase and/or adenylate cyclase in a variety of
      other tissues in addition to kidney and vasculature. ProANF 1-30, proANF 31-67,
      proANF 79-98, and ANF all increased rat lung, liver, heart and testes, but not
      spleen, particulate guanylate cyclase 2- to 3-fold at their 100 nM
      concentrations. Dose response curves revealed that maximal stimulation of
      particulate guanylate cyclase activity by these newly discovered peptides was at
      their 1 microM concentrations, with no further increase in activity above their 1
      microM concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352040
TI  - What is a chaperonin?

PMID- 1352041
TI  - [Rheumatoid arthritis and anemia; various aspects concerning prevalence,
      pathogenesis, diagnosis and therapy].

PMID- 1352044
TI  - The structure of celiprolol.
AB  - The crystal structure and nuclear magnetic resonance (NMR) spectra and
      assignments of celiprolol, N'-[3-acetyl-4[3-[N-t-butylamino-2
      hydroxypropoxy]phenyl]-N,N- diethylurea, are reported. Celiprolol crystallizes in
      the monoclinic space group, P2(1)/a, with a = 9.081(2), b = 13.800(4), and c =
      17.471(5) A and beta = 95.04(2)degrees. Structure was solved by direct methods;
      structure refinement to R of 0.058. Intermolecular hydrogen-bonding in the
      crystal is discussed. The 1H, 13C, and two-dimensional (2D) NMR spectra of the
      hydrochloride have been obtained and definitive signal assignments made.

PMID- 1352043
TI  - Major histocompatibility complex class I restriction fragment length polymorphism
      analysis in highly inbred chicken lines and lines selected for major
      histocompatibility complex and immunoglobulin production.
AB  - Selected chicken populations were analyzed by restriction fragment length
      polymorphism (RFLP) with a chicken MHC Class I (B-F) cDNA probe. The 13 highly
      inbred chicken lines differed in genetic origin and in MHC (B) haplotype, as
      distinguished by using hemagglutination with antisera against B-G and B-F
      antigens. The S1 sublines differed for B haplotype and antibody response to a
      synthetic polypeptide, GAT. In the highly inbred lines, band-sharing between
      lines from different origins was less than that between lines from same origin,
      showing the influence of the genetic background on chicken MHC Class I gene RFLP.
      In the S1 line, use of three restriction endonucleases (BglII, PvuII, and TaqI)
      produced MHC Class I RFLP patterns that were associated with B haplotype, but not
      with immune response to GAT (IrGAT). A previous study in the authors' laboratory
      also demonstrated an association of MHC Class II beta RFLP patterns with B
      haplotype, but not IrGAT, in the same line, suggesting that IrGAT is not
      controlled by MHC Class I or Class II beta genes.

PMID- 1352042
TI  - Regulation of P-glycoprotein gene expression in hepatocyte cultures and liver
      cell lines by a trans-acting transcriptional repressor.
AB  - Previously we have demonstrated that expression of the multidrug resistance (mdr)
      genes in rat liver and primary rat hepatocyte cultures is induced by exposure to
      2-acetylaminofluorene and 3-methylcholanthrene. The mdr expression induced by
      both of these compounds occurs primarily via increased gene transcription. To
      determine the nature of possible regulatory proteins involved in mdr gene
      regulation we inhibited protein synthesis using cycloheximide or emetine in
      primary rat hepatocyte cultures, mouse (HePa 1), human (Hep G2) and rat (H4-II-E)
      cell lines. Each cell type responded by strongly increasing its steady state mdr1
      mRNA levels. In hepatocytes increased mdr expression was observed after greater
      than 50% inhibition of protein synthesis, and was first detected after 2h of
      protein synthesis inhibition with maximal induction occurring by 24h. Nuclear run
      on analysis showed that the increased steady state mRNA level was due to
      increased gene transcription without alteration of the transcription start site.
      Combined these data indicate that one regulatory mechanism by which mdr gene
      expression is controlled is via a trans-acting transcriptional repressor.

PMID- 1352045
TI  - Physiological and Pharmacological Effects of Camellia sinensis (Tea): First
      Symposium. New York City, March 4-5, 1991.

PMID- 1352047
TI  - X-irradiation enhances in vitro human immunodeficiency virus replication
      correlation with cellular levels of cAMP.
AB  - Total body x-irradiation has been utilized in the treatment of several human
      diseases, including leukemia, where it is followed by bone marrow
      transplantation, and in some autoimmune disorders. Recently, it was reported that
      total body irradiation appeared useful in the treatment of Friend leukemia virus
      infection in mice. In this report, the effect of x-irradiation on the replication
      of human immunodeficiency virus (HIV) in vitro in CD4+ cells was examined. MT-4
      cells and HIV strain human T cell lymphotropic virus Type IIIB were used to
      conduct this study. Infected MT-4 cells were irradiated at the time of infection
      or following infection with x-ray doses of 25-300 cGy. Doses of 50, 150, and 300
      cGy enhanced HIV replication by 1.6-, 2-, and 4.8-fold, respectively. Irradiating
      the cells prior to infection also resulted in similar enhancement of HIV
      replication. This phenomenon was also observed with wild-type HIV isolates grown
      in peripheral blood mononuclear and in HIV chronically infected cells. In
      addition, the enhancement was associated with a radiation-induced increase in
      intracellular levels of cAMP. The use of the cAMP-dependent protein kinase A
      inhibitor, H-8, inhibited HIV replication by 65%. These data suggest that in
      vitro exposure to low doses of x-ray enhances HIV replication partially via a
      cAMP-dependent pathway.

PMID- 1352046
TI  - The binding of bombesin and somatostatin and their analogs to human colon
      cancers.
AB  - Specific receptors for bombesin/gastrin-releasing peptide, somatostatin, and EGF
      were investigated in 15 human colon cancer specimens. Eight of 15 clinical
      specimens (15%) of colon cancer showed the presence of somatostatin receptors.
      Octapeptide somatostatin analogs, RC-160 and RC-121, showed 10 times higher
      binding affinity for somatostatin receptors on colon cancer membranes than
      somatostatin. Analysis of 125I-Tyr4-bombesin binding data revealed the presence
      of specific binding sites in six (40%) specimens of human colon cancer. Scatchard
      analysis of 125I-labeled bombesin indicated a single class of receptors in three
      specimens with an apparent Kd value of 2.5 nM and two classes of receptors with
      high (Kd = 0.4 +/- 0.2 nM) and low affinity (Kd = 1.6 +/- 0.4 microM) in three
      other specimens. The 125I-Tyr4-bombesin binding capacities in the colon cancers
      for high affinity binding sites were from 6 to 228 fmol/mg protein and for low
      affinity binding sites 76 +/- 15 pmol/mg protein. None of the membrane
      preparations made from normal colonic mucosa specimens showed specific binding
      for 125I-Tyr4-bombesin. Five pseudononapeptide (psi 13-14) bombesin (6-14)
      antagonists, with different modifications at Positions 6 and 14, synthesized in
      our laboratory, inhibited the binding of 125I-Tyr4-bombesin in nanomolar
      concentrations. No correlation was found between the degree of differentiation
      and the presence of binding sites for somatostatin or bombesin. Specific binding
      of EGF was detected in 80% of colon cancer specimens. EGF binding capacity in
      colon cancer membranes was on average twice as high as in normal colon mucosa (50
      +/- 21 vs 28 +/- 14 fmol/mg protein, respectively). Specific binding sites for
      somatostatin and EGF, but not bombesin, were also demonstrated in human colon
      cancer cell line HT-29. In HCT-116 colon cancer line only EGF receptors were
      found. These receptor findings and our in vivo studies on inhibition of colon
      cancer growth support the merit of continued evaluation of somatostatin analogs
      and bombesin/gastrin-releasing peptide antagonists in the management of colonic
      carcinoma.

PMID- 1352048
TI  - Feeding behavior and ambulatory activity in rats with D-galactosamine-induced
      hepatic failure.
AB  - This study was undertaken to investigate changes in feeding behavior and
      ambulatory activity, in rats with D-galactosamine (D-GAL)-induced hepatic
      failure. D-GAL was administered (1000 mg/kg) IP at 1800, just before the dark
      phase. The first significant decrease of ambulatory activity in rats with hepatic
      failure was observed between 0000 and 0300 h. A significant increase in drinking
      behavior was observed between 1800 and 2100 h, and a significant decrease was
      observed between 2100 and 0300 h. A significant decrease in food intake occurred
      between 1800 and 2400 h. Thereafter, there was no difference in food intake. In
      conclusion, we demonstrated significant changes in ambulatory activity, drinking
      behavior and food intake produced by D-GAL. A wide variation in systems,
      including monoamine turnover, and amino acid disturbance could be expected in
      these animals, and such changes might also have contributed to the results
      observed.

PMID- 1352049
TI  - The Northwick Park 'Functional' Psychosis Study: diagnosis and outcome.
AB  - Three hundred and twenty-six consecutively admitted patients with functional
      psychotic illnesses to which no diagnostic classification had been applied were
      followed up after 2.5 years. They were examined in social, clinical and
      psychological terms and the CATEGO programme and DSM-III criteria were applied to
      data concerning the index episode to derive diagnostic classifications. The
      deterioration in occupational functioning and the hospital careers of patients
      with diagnostic classifications of schizophrenia were worse than those in the
      other groups and positive and negative features were also more severe in patients
      with a classification of schizophrenia. By contrast, no differences in
      psychological test performance were found between the groups based upon
      diagnostic classification. Impaired psychological test performance was found and
      it was strongly related to concurrent mental state abnormalities, particularly
      negative symptoms. It is concluded that the diagnostic classifications used were
      of limited value in predicting outcome in functional psychosis.

PMID- 1352050
TI  - A placebo controlled trial of remoxipride in the prevention of relapse in chronic
      schizophrenia.
AB  - Sixty-two DSM III chronic schizophrenic inpatients were selected for a double
      blind, placebo controlled, multi-centre, relapse prevention study of remoxipride,
      a selective dopamine (D2)-receptor antagonist. After a 1 month placebo washout,
      23 patients had relapsed and were withdrawn. Of the remaining patients 19 were
      randomised to remoxipride (150-300 mg daily) and 20 to placebo. Their median age
      was 58 years, 26 were male, and the median duration of illness was 33 years.
      After 24 weeks a further total of 8 remoxipride and 17 placebo patients had been
      withdrawn. Excluding three patients withdrawn for reasons other than relapse, the
      comparative relapse rates were 37% and 75%, respectively (P = 0.015). Efficacy
      analyses using clinical global impression (P = 0.04) and change in BPRS scores (P
      = 0.016) were in favour of remoxipride. Extrapyramidal symptoms were minimal in
      both groups. Treatment emergent adverse events were similar in the two groups.
      Remoxipride is therefore of potential value as a safe drug which is both
      effective and well tolerated in the long term management of chronic schizophrenic
      patients.

PMID- 1352051
TI  - Different neuroleptics show common dose and time dependent effects in
      quantitative field potential analysis in freely moving rats.
AB  - Under the assumption that field potentials recorded from particular brain areas
      reflect the net balance of neurotransmitter activities, the dose- and time
      dependent responses induced by intraperitoneal application of different
      neuroleptic drugs are quantified by spectral analysis of the electroencephalogram
      recorded from frontal cortex, hippocampus, striatum and reticular formation. The
      actions of haloperidol, chlorpromazine, clozapine, prothipendyl and thioridazine
      in general were characterized by increases of the spectral power in the alpha 1
      and beta range, at higher dosages also in the theta range. This observed pattern
      of changes is in line with the neuroleptic induced spectral changes reported in
      the literature for other animals and man. In the light of the already known
      effects of other psychoactive drugs on the frequency content of field potentials
      in the rat, it should now be possible to classify different drugs in terms of
      their clinical indication. With respect to the type of neurotransmitter control
      underlying the changes produced by various neuroleptics, it is quite obvious from
      the comparisons with the respective drug effects that dopamine-D1-receptor
      controlled transmission is not responsible for this action. On the basis of
      earlier findings a possible interaction between dopamine-D2 receptor or
      glutamatergic transmitter control is discussed.

PMID- 1352052
TI  - Effects of quinpirole and SKF 38393 alone and in combination in squirrel monkeys
      trained to discriminate cocaine.
AB  - The present study was designed to assess the behavioral similarity of the effects
      of prototype dopamine receptor-subtype selective agonists and cocaine. Squirrel
      monkeys (N = 4) were trained with food reinforcement to press one of two levers
      after administration of IV cocaine (0.3 mg/kg) or the other lever after saline.
      After training, IV cocaine produced reliable responding on the cocaine lever
      (greater than 98%), whereas saline produced reliable responding on the alternate
      lever (greater than 98%). The D2 agonist, quinpirole (0.003-1.0 mg/kg, IM),
      produced dose-related increases in cocaine-appropriate responding, with maximal
      effects of 62%. When delivered IV, quinpirole (0.01-0.17 mg/kg) was approximately
      twice as potent, but no more effective. The D1 agonist, SKF 38393 (0.3-30.0
      mg/kg, IM or 3.0-17.0 mg/kg, IV) failed to produce any significant cocaine
      appropriate responding. Further, pretreatment with SKF 38393 (either 0.3 or 10.0
      mg/kg, IM) did not significantly alter the the quinpirole (0.01-1.0 mg/kg, IM)
      dose-effect curve. The effects of these drugs differ from those previously
      reported in rats, suggesting a species difference that may be of importance in
      evaluating the behavioral pharmacology of cocaine.

PMID- 1352053
TI  - Long-term administration of m-chlorophenylpiperazine (mCPP) to rats induces
      changes in serotonin receptor binding, dopamine levels and locomotor activity
      without altering prolactin and corticosterone secretion.
AB  - Meta-chlorophenylpiperazine (mCPP) is a serotonin (5-HT) agonist with
      antidepressant actions. In order to investigate the effects of chronic mCPP
      treatment the drug was administered to rats for 15 days (5 mg/kg twice daily).
      Controls were administered saline. Long-term mCPP treatment led to a 36% increase
      in [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) binding to 5-HT1a
      receptors in hippocampus and a 74% decrease in [3H]ketanserin binding to 5-HT2
      receptors in cortex, while (-)[125I]iodocyanopindolol ([125I]CYP) binding to 5
      HT1b receptors in hypothalamus and striatum was unchanged. In hypothalamus,
      chronic mCPP treatment decreased the levels of dopamine (DA) but not 5-HT. The
      usual suppression of locomotor activity induced by acute mCPP administration was
      less after long-term mCPP treatment. Brain and plasma levels of mCPP following an
      acute dose were not different between controls and rats previously administered
      mCPP, suggesting that altered rate of metabolism of the drug did not explain the
      tolerance to the mCPP-induced decrease in locomotor activity. mCPP-induced
      prolactin (PRL) and corticosterone release were not changed by previous long-term
      mCPP administration. Thus, chronic mCPP administration to rats induced
      alterations in density of 5-HT receptor subtypes, hypothalamic levels of DA and
      locomotor behavior.

PMID- 1352054
TI  - Effects of remoxipride, a dopamine D-2 antagonist antipsychotic, on sleep-waking
      patterns and EEG activity in rats and rabbits.
AB  - The antipsychotic remoxipride, a selective dopamine D-2 receptor antagonist, was
      studied for its effects on sleep-waking patterns in the rat and
      electroencephalographic (EEG) activity in the rabbit. Haloperidol, which has
      lesser selectivity for D-2 receptors, was used for comparison. In the rat,
      remoxipride (1-10 mg/kg SC) did not affect either total sleep or non-rapid eye
      movement (non-REM) sleep. Only REM was slightly reduced by the high dose of 10
      mg/kg. Haloperidol (0.1-1 mg/kg PO) enhanced duration of both total sleep and non
      REM sleep. In the rabbit, remoxipride (3 and 10 mg/kg IV) induced no significant
      changes of the EEG power spectrum over 0.1-38.5 Hz or individual frequency bands.
      In both cortex and hippocampus the drug did not alter the arousal response to
      acoustic sensory stimuli. Plasma concentration of remoxipride 10 mg/kg IV in
      rabbits declined biexponentially and was 4 and 2 mumol/l at 30 min and 1 h,
      respectively. Haloperidol (0.3 and 1 mg/kg) slowed down the EEG activity,
      enhanced the power spectrum of the cortical and hippocampal activity, and
      significantly reduced the duration of arousal induced by sensory stimuli. The
      results indicate that, unlike haloperidol, remoxipride has weak or no sedative
      effects. The data also provide support to the notion that D-2 receptors are not
      involved in the regulation of states of sleep and sedation.

PMID- 1352055
TI  - Like diazepam, CL 218,872, a selective ligand for the benzodiazepine omega 1
      receptor subtype, impairs place learning in the Morris water maze.
AB  - The sedative, anxiolytic, and amnesic effects of diazepam were compared to those
      of CL 218,872, a triazolopyridazine that has a preferential affinity for the
      benzodiazepine omega 1 receptor subtype. Spontaneous locomotion was assessed
      using a running wheel, anxiety was assessed using an open-field divided into
      central and peripheral areas (thigmotaxis), and amnesia was assessed using the
      Morris water maze. It was found that CL 218,872, like diazepam, depressed
      spontaneous locomotion, reduced anxiety, and impaired place learning in a dose
      dependent manner. Flumazenil, a benzodiazepine receptor antagonist with a similar
      affinity for both omega 1 and omega 2 subtypes, reversed all of the effects of
      diazepam and antagonized the anxiolytic and amnesic effects, and some but not all
      of the sedative effects of CL 218,872. These results suggest that the selective
      activation of the omega 1 receptor subtype by CL 218,872 is sufficient to produce
      sedation, anxiolysis, and amnesia in a manner similar to that produced by the
      coactivation of both the omega 1 and omega 2 receptor subtypes with diazepam.

PMID- 1352056
TI  - 5-HT1C receptor antagonists have anxiolytic-like actions in the rat social
      interaction model.
AB  - The effects of a range of 5-HT receptor antagonists were examined in an animal
      model of anxiety--the social interaction test. Six antagonists with high affinity
      for 5-HT1C receptors; mianserin, (+) mianserin, 1-naphthyl piperazine, ICI 169
      369, pizotifen and LY 53857 all increased the time spent in active social
      interaction by pairs of weight-matched rats under high light unfamiliar
      conditions. As locomotion was only increased by 1-NP and then only at high doses,
      the effect of the drugs is consistent with anxiolysis. These properties were
      shared by the benzodiazepine anxiolytic chlordiazepoxide but not by the specific
      5-HT2 antagonists ketanserin and altanserin, nor by the 5-HT1A and 5-HT1B
      antagonists cyanopindolol and pindolol. Similarly, neither the adrenergic alpha 2
      antagonist idazoxan, the alpha 2 antagonist and putative 5-HT1D partial agonist
      yohimbine nor the H1 antagonist mepyramine had any significant effect. Since
      (+)mianserin, LY 53857 and ICI 169 369 at least have low affinity for 5-HT3
      receptors these receptors are also unlikely to be involved. The results therefore
      imply that the observed anxiolytic effects of the drugs are likely to be mediated
      by 5-HT1C receptor blockade.

PMID- 1352057
TI  - Genetic differences in the rewarding and activating effects of morphine and
      ethanol.
AB  - The influence of genotype on the rewarding and locomotor activating effects of
      morphine and ethanol was examined in the place conditioning paradigm. Two inbred
      mouse strains (C57BL/6J and DBA/2J) were exposed to a differential conditioning
      procedure in which each mouse received four pairings of a distinctive floor
      stimulus with IP injection of morphine (0, 2.5, 5 or 10 mg/kg) or ethanol (0, 1,
      2, 3 or 4 g/kg). A different floor stimulus was paired with saline. Conditioning
      trials lasted 30 min and each experiment concluded with a floor preference test
      in the absence of drug. In accord with previous studies, morphine evoked a dose
      dependent increase in activity during conditioning that was greater in C57BL/6J
      mice than in DBA/2J mice. In contrast, ethanol produced a dose-dependent increase
      in activity that was greater in DBA/2J than in C57BL/6J mice. Both strains showed
      conditioned place preference with morphine, but only the DBA/2J strain showed
      conditioned place preference with ethanol. No conditioned place aversion was
      seen. With both drugs, stronger place preference conditioning was obtained in
      DBA/2J mice, supporting the general conclusion that sensitivity to drug reward is
      influenced by genotype. The fact that the same genotype is more sensitive to the
      rewarding effects of two different drugs supports theories postulating
      commonality in the biological mechanisms of drug reward. Although the outcome of
      the ethanol study supports predictions of the psychomotor stimulant theory of
      addiction concerning the relationship between drug-induced activation and reward,
      the outcome of the morphine study does not.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352058
TI  - Comparison of acute and chronic treatment of various serotonergic agents with
      those of diazepam and idazoxan in the rat elevated X-maze.
AB  - The aim of this study was to use the elevated X-maze to compare acute and chronic
      treatments of a 5-HT1A partial agonist, ipsapirone, a 5-HT2 antagonist,
      ritanserin, and a 5-HT3 antagonist, ondansetron, with those of established
      anxiolytic (diazepam) and anxiogenic (idazoxan) compounds. Acute diazepam (5
      mg/kg IP) produced a significant increase in the percentage open:total entries
      and time and time spent in the end of the open arms (anxiolytic profile) on the
      elevated X-maze. Chronic treatment with diazepam (5 mg/kg IP twice daily for 14
      days) still produced an anxiolytic profile which was not apparent 24 h after
      cessation of chronic treatment (withdrawal). In contrast, idazoxan given both
      acutely (0.25 mg/kg IP) and chronically (0.8 mg/kg/h at a flow rate of 5.5
      microliters/h for 14 days, via osmotic minipumps) resulted in a significant
      decrease in the percentage open:total entries and time and time spent in the end
      of the open arms (anxiogenic profile). Acute administration of ipsapirone had no
      effect on any of the behavioural parameters at doses of 0.01 and 1 mg/kg IP,
      while 0.1 mg/kg IP produced a significant anxiogenic profile. Chronic treatment
      with ipsapirone (0.01, 0.1 and 1 mg/kg IP twice daily for 14 days) had no
      significant effect on rat behaviour on the X-maze but 24 h after ending
      treatment, ipsapirone at the highest dose used (1 mg/kg) produced a significant
      anxiogenic profile which was absent when the animals were tested 7 days after
      cessation of treatment. Ritanserin (0.05 and 0.25 mg/kg IP) had no effect acutely
      on any of the parameters measured but chronic treatment (0.25 mg/kg IP, twice
      daily for 14 days) produced a significant anxiolytic effect which was still
      present 24 h but not 7 days after cessation of treatment. Acute ondansetron
      (0.01, 0.1 and 1 mg/kg IP) had no effect while chronic ondansetron (0.01 mg/kg
      IP, twice daily for 14 days) produced a significant anxiolytic profile which was
      not a result of handling during the chronic dosing schedule, an effect was not
      measureable 24 h after treatment ended. The results demonstrate that the X-maze
      can detect anxiolytic activity in non-benzodiazepine drugs, as ritanserin and
      ondansetron showed anxiolytic profiles but only after chronic treatment. In
      contrast, the X-maze failed to detect any anxiolytic activity with the 5-HT1A
      partial agonist ipsapirone after either acute or chronic treatment.

PMID- 1352059
TI  - The Roman strains of rats as a psychogenetic tool for pharmacological
      investigation of working memory: example with RU 41656.
AB  - This study examined the effects of RU 41656, a dopaminergic D2 agonist, on the
      differential working memory performances and on the differential activities of
      the neurochemical systems of the Roman high (RHA) and Roman low (RLA) avoidance
      strains of rats. Compared with RLA, RHA performed worse in three tests of working
      memory (spontaneous alternation, radial maze and object recognition) and had
      higher levels of exploratory locomotor activity. Hippocampal and frontal cortex
      choline acetyltransferase (ChAT) activities were lower in RHA. Frontal cortex DA
      and DOPAC levels, hippocampal and striatal 5-HT and NA levels were higher in RHA.
      RU 41656 induced a significant improvement in working memory performance of RHA,
      whereas in RLA it had no effect. It decreased exploratory locomotor activity in
      both strains. ChAT activity in hippocampus was not affected by RU 41656 in either
      strain, whereas in frontal cortex it was increased in RHA but not in RLA.
      Hippocampal NA levels were decreased by RU 41656 in RHA but not in RLA. These
      results confirm previous data concerning the promnesic effect of RU 41656 and
      extend the finding that the Roman strains are a psychogenetic model for the
      behavioural, neurochemical and psychopharmacological study of the working memory
      in rats.

PMID- 1352062
TI  - [Pneumology Conference of French Language. Strasbourg, 4-6 June 1992. Abstracts].

PMID- 1352061
TI  - Stress and arousal in sedative and stimulant cigarette smokers.
AB  - Self-reported feelings of stress and arousal were assessed in 18 sedative and 9
      stimulant smokers, over a typical day of smoking. Prior to each cigarette, self
      ratings of stress and arousal were recorded on a brief adjective check list.
      These self-ratings were then repeated following cigarette smoking. These diary
      data were split into four blocks to represent: first cigarette of the day, second
      quartile cigarette, third quartile cigarette, and last cigarette of the day.
      Analysis of variance revealed significant effects of smoking on both stress and
      arousal. Self-rated feelings of stress were significantly reduced following
      cigarette smoking (P less than 0.002); this was found with both subjects groups
      and across all cigarette blocks. Cigarette smoking also led to increased feelings
      of arousal (P less than 0.01), although these changes in arousal differed between
      subject groups (drug x type-of-smoker interaction: P less than 0.03). Stimulant
      smokers showed higher levels of arousal after smoking, across all four cigarette
      blocks. Sedative smokers showed a slight increase in arousal only after their
      first cigarette. These findings were not as predicted by the arousal modulation
      theory of cigarette smoking, which suggests that changes in stress and arousal
      are interdependent. Instead they show that smoking affects stress and arousal in
      quite different ways. Stress and arousal should therefore be recognised as
      independent dimensions within smoking/nicotine research.

PMID- 1352060
TI  - Modulation of MK-801 response by dopaminergic agents in mice.
AB  - Various doses of the non-competitive N-methyl-D-aspartate (NMDA) receptor
      antagonists, MK-801 (0.1-0.5 mg/kg) and ketamine (2.5-10 mg/kg), produced a dose
      dependent increase in stereotypic behaviour in naive mice. MK-801 (0.1 mg/kg) and
      ketamine (2.5 mg/kg) potentiated the stereotypic response of apomorphine (0.1-0.5
      mg/kg) in mice pretreated with reserpine (5 mg/kg, 24 h prior) and alpha-methyl-p
      tyrosine (150 mg/kg, 1 h prior) but not in naive mice. SKF 38393, a D1 dopamine
      agonist, enhanced whereas B-HT 920, a D2 dopamine agonist, reduced the
      stereotypic response of MK-801 in naive mice. The response of MK-801 was blocked
      by pretreatment with haloperidol (0.5 mg/kg), molindone (2.5 mg/kg), clozapine
      (7.5 mg/kg) and SCH 23390 (0.1 mg/kg). The present data suggest involvement of
      endogenous DA transmission in the stimulant action of non-competitive NMDA
      antagonists in mice. Dopamine D1 and D2 receptor stimulation, respectively, exert
      opposing effects on the behavioral expression of MK-801 in mice.

PMID- 1352063
TI  - Reactivity of gamma delta T cells induced by the tumour cell line RPMI 8226:
      functional heterogeneity of clonal populations and role of GroEL heat shock
      proteins.
AB  - The human tumour cell lines RPMI 8226 and Daudi are potent inducers of V gamma 9
      expressing T cells. The inducing element of RPMI 8226 has not been defined but
      evidence suggests that a member of the GroEL heat shock protein (HSP) family (HSP
      58) may have a role in the induction by Daudi cells. The present study examined
      the reactivity patterns of gamma delta T-cell clones generated in response to
      RPMI 8226 and addressed the possible role of HSP 58 in this process. RPMI 8226
      induced a population of V gamma 9 TCR+ cells which were heterogeneous in terms of
      their cell surface markers, patterns of proliferation and cytotoxic responses.
      All clones expressed CD3, CD2, CD18 and CD29. They demonstrated variability in
      expression of CD56, CD8 and HLA-DR. RPMI 8226 stimulated proliferation in
      purified bulk gamma delta cultures and clones. Daudi was also capable of inducing
      these cells to proliferate while mycobacterial products were not effective. The
      clones demonstrated a limited non-MHC-restricted cytotoxicity pattern with some
      evidence of clonal heterogeneity. Although both Daudi and RPMI 8226 were
      sensitive to lysis by the clones, cold inhibition experiments indicated
      differential activity towards these targets. Anti-HSP 58 was inhibitory to gamma
      delta T-cell induction by RPMI 8226, Daudi and mycobacterial products. However,
      the anti-HSP 58 antibody appears to bind to the surface of at least six different
      tumour cell lines with no correlation to their ability to induce gamma delta T
      cells and the anti-HSP 58 inhibited non-gamma delta responses.

PMID- 1352064
TI  - Nearly identical T-cell receptor V-gene usage at birth in two cohorts of
      distinctly different ethnic origin: influence of environment in the final
      maturation in the adult.
AB  - We have previously analysed the T-cell receptor (TCR) V-gene usage in peripheral
      blood T lymphocytes from a group of healthy Scandinavians, and described a biased
      representation (i.e. a statistically significant higher median representation)
      for some of the TCR V genes towards the CD4+ subpopulation. In a subsequent study
      the usage of the same V genes was analysed in single positive (CD4+ CD8- and CD4-
      CD8+) human thymocytes, and a similar type of skewness was noted. These
      observations might be explained by an influence of the specificity of the TCR of
      thymocytes on the maturation into the CD4+ or the CD8+ lineage. Such a model
      would assume an interaction between a common determinant on the major
      histocompatibility complex (MHC) class I or class II molecules, or with a peptide
      that is preferentially presented by either of the two molecules, and the TCR on
      the maturing thymocyte. To investigate the possible influence of a different
      genetic background and environment on skewed TCR V-gene representation, we have
      in this study analysed the TCR V-gene usage in peripheral blood and umbilical
      cord blood lymphocytes obtained from Asians, with a different ethnic and
      environmental background from our previous Scandinavian subjects. In the
      umbilical cord blood lymphocytes the TCR V-gene usage was close to identical
      between the two different ethnic groups in both CD4+ and CD8+ subpopulations.
      Analysing the peripheral blood lymphocyte (PBL) TCR V-gene usage, we found that
      three of the four monoclonal antibodies (MoAb) with a biased reactivity towards
      the CD4+ subpopulation in the Scandinavian group also showed a similar skewed
      reactivity in this study. Thus, the majority of the TCR V genes were used in a
      similar way. Some minor but definite discrepancies could be detected when
      comparing TCR V-gene usage in adult individuals from these two different ethnic
      groups. These differences could be inferred to be due to selective peripheral
      expansion through environmental pressure of T cells utilizing a specific V beta
      gene segment. We conclude that a striking preservation of biased TCR V-gene usage
      does exist in humans of distinctly different ethnic origin.

PMID- 1352065
TI  - Neurotransmitter release from synaptotagmin-deficient clonal variants of PC12
      cells.
AB  - Synaptotagmin (p65) is an abundant synaptic vesicle protein of neurons and
      contains regions similar to the regulatory domain of protein kinase C. These
      domains are thought to be involved in calcium-dependent interaction with membrane
      phospholipids during exocytosis. To assess the functional role of synaptotagmin,
      synaptotagmin-deficient clonal variants of PC12 cells were isolated. All of the
      variant cells released catecholamine and adenosine triphosphate in response to
      elevated intracellular concentrations of calcium, which suggests that
      synaptotagmin is not essential for secretion of catecholamine and adenosine
      triphosphate from PC12 cells.

PMID- 1352066
TI  - Involvement of the N-methyl D-aspartate (NMDA) receptor in synapse elimination
      during cerebellar development.
AB  - In many instances, the establishment of highly specific neuronal connections
      during development results from the rearrangement of axonal projections through
      the trimming of exuberant collaterals or the elimination of functional synapses
      or both. Although the involvement of the N-methyl D-aspartate (NMDA) subtype of
      the glutamate receptor has been demonstrated in the shaping of axonal arbors, its
      participation in the process of selective stabilization of synapses remains an
      open issue. In this study, the effects of chronic in vivo application of D,L-2
      amino-5-phosphonovaleric acid (D,L-APV), a selective antagonist of the NMDA
      receptor, on the synapse elimination process that takes place in the developing
      cerebellum of the rat have been analyzed. D,L-APV treatment prevented the
      regression of supernumerary climbing fiber synapses in 49 percent of the recorded
      Purkinje cells, while the inactive isomer L-APV was ineffective. Thus, activation
      of the NMDA receptor is a critical step in the regression of functional synapses
      during development.

PMID- 1352068
TI  - The antithrombin III gene polymorphism in Japan: examination for haplotypes
      relevant to disordered antithrombin III biosynthesis.
AB  - In the human antithrombin III (AT III) gene of Caucasian, two restriction
      fragment length polymorphism (RFLPs) have been identified and used for the
      linkage analysis of many congenital AT III abnormality and deficiency. In the
      present study, we attempted to examine the existence and distribution of these
      RFLPs in Japanese and utilize them for the molecular survey of the members in the
      AT III Toyama kindred and 4 type Ia deficient families. An AT III cDNA clone was
      isolated by ourselves and served as a hybridization probe. In Japanese, the
      intragenic polymorphism, which is referred to + and - alleles, was evenly
      distributed (.49: .51), and the 5'-length polymorphism, designated as S and F
      alleles, was also conserved at a ratio of .4 to .6. However, the combined
      genotypes of both polymorphisms revealed disproportionate, and + and S, and - and
      F alleles seemed mainly to coexist. AT III genes of the AT III Toyama kindred
      showed the homozygous genotype of -/F, and all affected members of the deficient
      families demonstrated no distinguishable alterations on Southern blots,
      suggesting that a subtle defect in the AT III gene or the "trans-acting"
      disordered mechanism is responsible for the decreased AT III levels. According to
      some reports that a defective AT III gene is the cause of inherited AT III
      deficiency, it was implied that the abnormal AT III gene was located on the
      haplotype of -/F in 3 families and +/F in one. In two deficient families with
      heterozygous genotypes, the RFLPs were considered to bring a clue to determine
      the structural changes.

PMID- 1352069
TI  - Abstracts of the 12th International Congress on Thrombosis. Florence, May 18-23,
      1992.

PMID- 1352067
TI  - Expression of intra-MHC transporter (Ham) genes and class I antigens in diabetes
      susceptible NOD mice.

PMID- 1352070
TI  - [Proceedings of the VI All-Russian Congress of Roentgenologists and Radiologists
      (Radiodiagnosis). Samara, 18-22 May 1992. Abstracts].

PMID- 1352071
TI  - Glomerular extracellular matrices in rat diabetic glomerulopathy by scanning
      electron microscopy.
AB  - Characteristic pathological changes in the glomeruli in diabetic nephropathy
      include expansion of the mesangial matrix and thickening of the glomerular
      basement membrane (GBM). Using an acellular digestion technique combined with
      scanning electron microscopy, the three-dimensional ultrastructural changes in
      glomerular extracellular matrices were studied in rats with diabetic
      glomerulopathy. Diabetes was induced by the intravenous injection of
      streptozotocin and morphological analyses were performed 3, 6 and 11 months after
      the injection. Expansion of mesangial area and GBM thickening became evident with
      time. After treatment with the series of detergents, all cellular components were
      completely removed leaving the extracellular matrices intact. In normal controls,
      the mesangial matrix appeared as fenestrated septa with oval or round stomata
      between the glomerular capillaries. In diabetic glomerulopathy, expansion of
      mesangial matrix and narrowing of the mesangial fenestrae were observed. These
      changes in the mesangial matrices seem to play a vital role in the progression of
      glomerulosclerosis in rat diabetes. A subendothelial thin layer of the GBM was
      continuous with the mesangial matrix. One cause of GBM thickening in
      streptozotocin diabetes may be expansion of the mesangial matrix into the
      peripheral GBM.

PMID- 1352073
TI  - Glycogen phosphorylase hyperactive foci of altered hepatocytes in aged rats.
AB  - In untreated 12- to 24-month-old rats, the enzyme histochemical pattern of 45
      focal hepatic lesions was investigated in serial sections. In addition to
      previously characterized glycogen storage foci, a new type of enzymatically
      altered hepatic focus was found. The outstanding feature of this was an increased
      glycogen phosphorylase activity. The frequent appearance of glycogen
      phosphorylase hyperactive foci simultaneously exhibiting excessive glycogen
      storage suggests a close relationship to the well known glycogen storage foci
      representing an early stage in the sequence of cellular changes which lead to
      hepatic tumors.

PMID- 1352072
TI  - Epithelial differentiation in gliomas, meningiomas and choroid plexus papillomas.
AB  - The immunohistological findings using antibodies to different intermediate
      filaments (glial fibrillary acidic protein, vimentin and two types of
      cytokeratin) and epithelial membrane antigen are described in 89 gliomas, 19
      meningiomas and 8 choroid plexus papillomas (CPPs) from adult patients. All the
      patients had total or subtotal surgical excision of their tumours with clinical
      follow up for between 3 and 7 years. The immunohistological results were
      correlated with the histological features and patient survival. Tumours other
      than low grade astrocytomas, oligodendrogliomas and anaplastic ependymomas
      expressed one or more epithelial markers. This immunohistological evidence of
      epithelial differentiation in the absence of histological epithelial features in
      gliomas confirms that the two are not necessarily correlated. It is concluded
      that the expression of epithelial markers in some intradural tumours may reflect
      aberrant differentiation related to the degree of anaplasia in poorly
      differentiated astrocytomas and glioblastomas. All the patients with anaplastic
      epithelial marker-positive gliomas died within 1 year, whereas only 68% of
      patients with marker-negative tumours died within the follow-up period. In
      ependymomas and meningiomas, the expression of epithelial markers may reflect
      their histogenesis, while in malignant CPPs such expression could denote either
      their aberrant differentiation or histogenetic derivation.

PMID- 1352074
TI  - Immunopathology of alkaline phosphatase-induced granulomatous hepatitis in rats.
AB  - Granulomatous inflammation is a specific type of chronic inflammation in which
      macrophages and T-cell-mediated immunity to the inciting agent play a pivotal
      role. In the present study, granulomatous hepatitis was induced in rats by the
      administration of a single intravenous dose of porcine intestinal alkaline
      phosphatase. The cellular composition of the hepatic granulomas was analyzed in
      situ with a number of recently developed mouse anti-rat monoclonal antibodies to
      cells of the monocyte-macrophage lineage and lymphocyte subsets. Well-developed
      granulomas consisted of aggregates of macrophages with central modification into
      epithelioid cells, a peripheral rim of T- and B-lymphoid cells, including
      considerable numbers of immunoblasts and plasma cells. In addition, the periphery
      of the granulomas contained many fat storing cells, a sinusoidal cell type
      thought to play a central role in hepatic fibrosis. Moreover, intense
      immunostaining for the extracellular matrix proteins fibronectin and collagen
      type III was observed at the periphery of the lesions. The granulomas persisted
      for long periods without eliciting liver cirrhosis. Alkaline phosphatase induced
      hepatic granulomas in the rat may help to elucidate the contribution of cells of
      the B-lineage to chronic granulomatous inflammation.

PMID- 1352075
TI  - Centrifugal separation of carcinoma or atypical cells in voided urine.
AB  - A simple density gradient method was used to separate atypical and cancer cells
      from non-cancer cells in voided urine from patients with transitional cell atypia
      (moderate and grave atypia) and bladder cancer (squamous cell carcinoma and
      transitional cell carcinoma). Prior to cell separation, the Saccomanno preserved
      cells were dispersed by homogenization. After cell separation (5 min x 1400 rpm),
      atypical and cancer cells were enriched up to 20-fold. Also, most of the
      leucocytes (68-98%) and squamous cells (47-82%) were absent from density gradient
      specimen fractions containing the largest percentages of atypical and cancer
      cells. Peak purity ranges of atypical or cancer cells from different sample
      classes showed a large degree of overlap. This permitted the pooling of density
      gradient fractions enriched for atypical or cancer cells, thus increasing the
      efficiency of the method. Also, following centrifugation, the Papanicolaou
      stained specimen fractions showed less background staining than the unprocessed
      controls, and the cells retained diagnostic morphologic features. We infer that
      this method may be a useful, low-cost approach for the morphologic study of
      developing cancers, not only from the urinary bladder, but also from the
      respiratory tract.

PMID- 1352076
TI  - The Epstein-Barr virus encoded membrane protein (LMP) induces phenotypic changes
      in epithelial cells.
AB  - The Epstein-Barr virus (EBV)-encoded membrane protein, LMP, is expressed in a
      proportion of undifferentiated nasopharyngeal carcinomas (NPC). Previous studies
      have shown that the transfection of the gene encoding LMP into a human
      keratinocyte line, RHEK-1, induces morphological alterations and a reduced
      expression of cytokeratins. We have analyzed immunophenotypic changes in the RHEK
      1 line following LMP-transfection and compared these changes with the phenotype
      of NPC biopsies. We demonstrate a downregulation of two epithelial markers, an
      epithelial glycoprotein (EGP) defined by the monoclonal antibody Ber-EP4 and the
      epithelial membrane antigen (EMA). Furthermore, a lymphocyte activation
      associated antigen, CDw70 antigen, which was absent from the parental line was
      expressed in virtually all LMP-transfected cells, whereas no similar effect was
      seen with respect to the CD30 activation antigen. Nine EBV-positive human NPCs,
      six of which were LMP-positive expressed the EGP and EMA. The CDw70 antigen,
      which is not normally present in epithelial cells, was expressed in eight
      biopsies, whereas the CD30 antigen was not detectable. Our findings are in
      keeping with the notion that LMP expression may contribute to the immunophenotype
      of human NPCs.

PMID- 1352077
TI  - c-myc mRNA expression in non-Hodgkin's lymphomas.
AB  - Steady state c-myc mRNA levels determined by Northern blot analysis were examined
      in non-Hodgkin's lymphomas (NHL) of both high (n = 29) and low malignancy (n =
      18), and in non-specific chronic lymphadenitis (n = 6). High grade NHL,
      classified according to the updated Kiel classification, revealed significantly
      larger amounts of c-myc mRNA compared with low grade NHL and lymphadenitis. mRNA
      levels in non-specific lymphadenitis were lower than in low grade NHL, but the
      differences were not statistically significant. No correlation between c-myc mRNA
      levels and the immunologic phenotype was discernible. Growth fractions of the NHL
      were determined by immunostaining with the monoclonal antibody Ki-67. Significant
      correlations between the percentages of Ki-67-positive cells, as well as the
      amounts of c-myc mRNA, and classification into high or low grade NHL were found.
      However, the percentage of Ki-67 positive cells and c-myc mRNA levels in
      individual cases and in the various histologic entities of NHL did not correlate.
      Our results indicate the overexpression of the c-myc gene in NHL, and a highly
      significant correlation of steady state c-myc mRNA levels with the prognosis
      related histomorphologic Kiel classification of NHL into different subgroups of
      low and high grade malignancy.

PMID- 1352078
TI  - Arguments against the prostatic origin of the R-3327 Dunning H tumor.
AB  - The Dunning tumor, originally described as a carcinoma of the rat dorsal
      prostate, has for long been used as an experimental model of prostatic cancer. We
      have recently presented a number of morphological findings that are incompatible
      with the prostatic origin of the H-subline of the Dunning tumor. In this paper,
      biochemical and immunohistochemical markers of rat prostate and mammary gland are
      studied in the R-3327 Dunning H tumor. Pieces of the H tumor were inoculated in
      male or lactating female rats. The electrophoretic protein pattern of Dunning
      tumor extracts was more similar to that of the mammary gland than the
      dorsolateral prostate. Proteins selectively appearing after metabolic labeling in
      Dunning tumors grown in lactating rats corresponded to labeled proteins in
      mammary glands from the same animals. Secretory proteins typical of the lateral
      prostate (SVS II) and dorsal prostate (transglutaminase) could not be detected
      immunohistochemically in the Dunning tumor. Western blot studies of tumor
      extracts and slot blot analysis of RNA preparations from the tumor confirmed the
      absence of SVS II and prostate specific transglutaminase from the Dunning tumor.
      On the other hand, the presence of mammary gland proteins such as milk fat
      globule membrane proteins, lactoperoxidase and lactalbumin were detected in the
      Dunning tumor by immunohistochemistry and Western blotting, but were absent from
      the dorsolateral prostate. Transferrin-mRNA, expressed in the male urogenital
      tract and also in the liver and other tissues, was detected in the mammary gland
      and Dunning tumor, but not in the dorsolateral prostate. The absence of mammary
      gland secretory beta-casein in the Dunning tumor was related to the elevated Ha
      ras oncogene expression in the tumor, previously reported to suppress casein
      expression. The findings clearly demonstrate that the prostate cannot be the
      origin of the Dunning tumor, presently being used in prostatic cancer research.
      The designation prostatic adenocarcinoma for this tumor is therefore invalid.
      Furthermore, the data support our view that mammary gland might be the origin of
      the Dunning tumor, although the derivation from the bulbourethral or the parotid
      glands cannot strictly be excluded.

PMID- 1352079
TI  - [Beta blockers in heart failure?].

PMID- 1352080
TI  - Prolonged QT interval in neonates: benign, transient, or prolonged risk of sudden
      death.
AB  - To determine the factors relating to prognosis, the records of 15 neonates with
      persistent prolongation of the QT interval on the electrocardiogram after the
      fourth day of life were reviewed. Patients were admitted for symptoms (syncope,
      cardiac failure, or seizures), abnormal auscultation with an irregular heart rate
      or bradycardia, or because of a family history of a long QT syndrome. All infants
      had a long QTc, ranging from 0.46 to more than 0.70 second. Eight patients who
      had a QTc over 0.60 second developed severe ventricular arrhythmias (torsades de
      pointes, ventricular tachycardia) or second-degree AV block. Twelve of 15 were
      treated with beta-blocking agents, combined with ventricular pacing in five
      cases. Four infants died in the first month of life; they all had a very long QT
      interval and had experienced ventricular arrhythmias and AV block. Six children
      are still being treated with beta-blocking agents for the long QT syndrome and
      are doing well. In five infants, electrocardiographic abnormalities were
      transient and the QT interval returned to normal within 1 year. Therefore (1)
      prolongation of the QT interval in neonates may be transient or may represent an
      early form of the long QT syndrome and (2) the length of the QT interval may
      provide data on prognosis: those with a QTc less than 0.50 second returned to
      normal; those with a QTc greater than 0.60 second were associated with severe
      arrhythmias and four of eight infants died.

PMID- 1352081
TI  - Conference examines weight loss in America.

PMID- 1352082
TI  - Very-Low-Calorie Diets. Proceedings of a satellite symposium to the 6th
      International Congress on Obesity. Kyoto, Japan, October 18-21, 1990.

PMID- 1352083
TI  - A multicenter, double-blind, randomized, placebo-controlled comparison of
      nocturnal roxatidine in the treatment of active duodenal ulcer disease.
      Multicenter Roxatidine Cooperative Study Group.
AB  - This multicenter randomized, double-blind, 4-wk study compared the new H2
      receptor antagonistic roxatidine (R) to placebo (P) for treatment of
      endoscopically diagnosed active duodenal ulcer disease. Subjects were evaluated
      after 2 and 4 wk of treatment. Those whose ulcer was unhealed at 2 wk received 2
      more weeks of treatment before final evaluation. Ulcer healing (endoscopically
      determined) with roxatidine was more effective than placebo at both wk 0-2 (R =
      33.9%, P = 21.9%, p = 0.018) and wk 2-4 (R = 68.2%, P = 29.7%, p less than
      0.001), with an overall 4-wk effectiveness of 78.9% compared to 44.8% (p less
      than 0.001). At the end of treatment, average maximum ulcer diameter diminished
      83% in R and 50% in P (p less than 0.001). Roxatidine was also more effective
      than placebo in decreasing abdominal pain (p less than 0.001), decreasing the
      number of antacid tablets taken for pain relief (p less than 0.001), improving
      dyspeptic symptoms (p less than 0.001), and permitting return to a normal routine
      for subjects with previous illness-imposed restrictions on work and/or other
      daily activities. The profile of laboratory values and adverse experiences
      demonstrated roxatidine to be safe and well-tolerated. The efficacy of roxatidine
      as evaluated by the healing rate of duodenal ulcer and reduction in abdominal
      pain emphasize its value as an addition to the family of H2-receptor antagonists.

PMID- 1352084
TI  - Kinetics of L-glutamate influx in single barnacle muscle fibers under 0-trans
      conditions.
AB  - The dependence of L-glutamate influx on extracellular Na and L-glutamate
      concentrations was determined using internally dialyzed single muscle fibers of
      Balanus nubilus. Internal Na and glutamate concentrations were held at zero, and
      the cell membrane potential was constant. Flux activation curves for external
      glutamate were measured for five different external Na concentrations, and flux
      activation curves for external Na were measured independently for three different
      external glutamate concentrations. An analysis of alternative kinetic models for
      the transporter mechanism was made and led to the conclusions that under 0-trans
      conditions the Na:glutamate stoichiometry is 1:1, that glutamate first binding to
      the external transporter binding site is the preferred order under most
      extracellular conditions, and that the Na:glutamate coupling is too tight to
      permit measurable Na-independent glutamate uptake by the transporter.

PMID- 1352085
TI  - Ontogeny of prolyl endopeptidase, pyroglutamyl peptidase I, TRH, and its
      metabolites in rat pancreas.
AB  - We demonstrate that two enzymes, soluble unspecific pyroglutamyl peptidase I and
      prolyl endopeptidase, able to degrade thyrotropin-releasing hormone (TRH) in
      vitro were present in pancreas at the early stage of rat development. Specific
      particulate pyroglutamyl peptidase II remained undetectable during ontogenesis.
      Pyroglutamyl peptidase I specific activity increased until day 3 and decreased
      after day 5. Furthermore, prolyl endopeptidase specific activity rose slightly to
      a peak on postnatal day 20. A good correlation between immunoreactive TRH and
      deaminated TRH (TRH-OH) was found in the 1st wk after birth. However, His-Pro
      diketopiperazine (DKP) levels were stable and low during development. We show
      that hot acidic extraction conditions could artefactually generate His-Pro DKP.
      In vivo, active site-directed inhibitors of pyroglutamyl peptidase I and prolyl
      endopeptidase enzymes do not show any TRH-deamidating and/or pyroglutamyl
      peptidase I pathways in neonatal rat pancreas. The data suggest that these two
      enzymes are not involved in intra- or extracellular control of TRH levels in
      neonatal rat pancreas and that pancreatic TRH content appears to be principally
      regulated by biosynthetic steps. Nevertheless, low levels of endogenous His-Pro
      DKP and TRH-OH identified in neonatal rat pancreas suggest that TRH or TRH-like
      peptides may be metabolized in this tissue in intact rats, albeit at low rates.

PMID- 1352086
TI  - Characterization of a membrane tyrosine phosphatase in AR42J cells: regulation by
      somatostatin.
AB  - A phosphotyrosyl protein phosphatase (PTPase) activity has been characterized in
      the plasma membranes of confluent AR42J pancreatic tumor cells using 32P-labeled
      poly(Glu, Tyr) as substrate. Membrane PTPase activity exhibited an apparent
      Michaelis constant of 3 microM and an apparent maximal velocity of 0.9 nmol.min
      1.mg-1. It was inhibited by orthovanadate, zinc, poly(Glu,Tyr) and was stimulated
      by EDTA and dithiothreitol. Gel filtration of solubilized plasma membranes gave a
      peak of enzyme activity at a relative molecular weight of 70,000. Plasma membrane
      PTPase activity was changed during AR42J cell growth. At the beginning of
      culture, the control PTPase activity was minimal. Over the 5 days of culture,
      PTPase activity increased to reach a maximum (3.5-fold over control activity)
      preceding confluency by 2 days. Then the high level of PTPase activity was
      sustained until confluency. Incubation of the cells with the stable somatostatin
      analogue SMS 201-995 (SMS) resulted in a rapid and transient activation of crude
      membrane PTPase activity. Activation reached a maximum level within 5 min of
      addition and return to control levels within 20 min. The effect of SMS was dose
      dependent with half-maximal and maximal activation occurring at 6 pM and 0.1 nM
      SMS respectively.

PMID- 1352087
TI  - Regulation of brush-border enzyme activities and enterocyte migration rates in
      mouse small intestine.
AB  - We adapted the Weiser method, previously used to fractionate enterocytes of rat
      and rabbit intestine, to the much smaller intestine of mice. By histological,
      morphometric, enzymatic, histochemical, and immunocytochemical evidence, the
      method succeeded in removing mouse enterocytes sequentially along the crypt
      villus axis while preserving cell viability and minimizing mixing among cell
      fractions. Activities of three brush-border enzymes [alkaline phosphatase (AP),
      sucrase, and gamma-glutamyl transpeptidase (GGP)] varied simultaneously with
      dietary substrate level, intestinal region, and position along the crypt-villus
      axis. All three enzymes proved to be stimulated by dietary substrate: sucrase by
      dietary sucrose, AP and GGP by dietary protein. We also studied cell migration
      rates and life-times by autoradiography and by our modified Weiser method. By
      both methods, injected [3H]thymidine after short times was virtually confined to
      crypt cells, whereas after 40-48 h it was distributed from the crypt over the
      whole villus except for the villus tip. Villus height decreased twofold from
      duodenum to ileum, parallel to the regional decrease in cell migration rates
      because the cell lifetime of 68 h was independent of region. When we varied
      dietary carbohydrate and protein levels reciprocally while maintaining protein
      above the maintenance level, both cell migration rate and cell lifetime proved
      independent of diet.

PMID- 1352088
TI  - Locus ceruleus modulates migrating myoelectric complex in rats.
AB  - The role of the locus ceruleus (LC) in the control of migrating myoelectric
      complex (MMC) was investigated in rats with lesions induced by injections of 6
      hydroxydopamine (6-OHDA). Control animals received the vehicle alone. MMC was
      recorded in conscious rats chronically fitted with electrodes. After 6-OHDA was
      injected into the LC, lesions of the LC were total, partial (mostly rostral), or
      ineffective. The MMC period was significantly longer in animals with a total or
      partial lesion but was unchanged in animals with an ineffective lesion. No lesion
      of other brain noradrenergic nuclei was observed. The longer MMC period is
      comparable to that obtained after intracerebroventricular injection of 6-OHDA,
      which is responsible for a more diffuse destruction of brain noradrenergic
      systems, including LC itself. Bilateral lesions of the central tegmental tract,
      which carries ascending noradrenergic axons from the medullary and pontine cell
      groups outside the LC, do not alter the MMC cycle. Consequently, the LC is most
      likely the major brain noradrenergic candidate for modulating the MMC pattern in
      rats.

PMID- 1352089
TI  - Effect of vitamin D status on the rapid actions of 1,25-dihydroxycholecalciferol
      in rat colonic membranes.
AB  - Recent studies from our laboratory have demonstrated that the in vitro addition
      of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] rapidly (seconds to minutes)
      stimulated membrane phosphoinositide turnover, translocated protein kinase C from
      the cytosolic to particulate fraction, increased cytosolic calcium ([Ca2+]i), and
      decreased cytoplasmic pH (pHi) via inhibition of Na(+)-H+ exchange in rat colonic
      epithelium of dietary vitamin D-sufficient rats and in Caco-2 cells. In contrast
      to these prior findings, in the present experiments, 1,25(OH)2D3 failed to elicit
      any of these colonic biochemical responses in vitamin D-deficient animals.
      Bethanechol chloride also failed to alter this signal transduction pathway,
      [Ca2+]i, or pHi. In vivo administration of this hormone for 5-7 days, moreover,
      to vitamin D-deficient animals restored the rapid biochemical effects of in vitro
      1,25(OH)2D3 and bethanechol chloride. These studies, therefore, indicate that
      alterations in the vitamin D status of rats modulate the action of 1,25(OH)2D3
      and other agents on the colonic phosphoinositide signal transduction system and
      on [Ca2+]i, which, in turn, may influence important cellular processes in this
      organ such as Na(+)-H+ exchange.

PMID- 1352090
TI  - The absence of teratogenic effects of some analgesics used in anaesthesia.
      Additional evidence from a mouse model.
AB  - The possibility exists that agents used in anaesthesia may have adverse
      teratogenic effects on staff, patients, and developing fetuses. It has been shown
      that a range of neurotropic drugs, when injected into pregnant mice on the 9th
      day of gestation, produce a characteristic group of central nervous system
      malformations in their fetuses. We have studied the possible teratogenicity of
      pethidine, fentanyl, phenoperidine and lignocaine when tested in this way and
      conclude that they appear to have less effect than other neurotropic drugs
      previously tested.

PMID- 1352091
TI  - Esmolol and clonidine--a possible interaction.

PMID- 1352092
TI  - Thymic carcinoid in association with MEN syndromes.
AB  - Although carcinoid tumors in association with multiple endocrine neoplasia
      syndrome (MEN) has been well described, thymic carcinoid in association with MEN
      is extremely rare (only 23 cases in the world literature). A patient with thymic
      carcinoid and MEN-I was treated with surgical resection and postoperative
      radiation therapy, which was later followed by subtotal parathyroidectomy for
      hyperparathyroidism. Four years later, a symptomatic recurrence of his thymic
      carcinoid was resected from below his right clavicle. Six years after his
      original operation, the patient came to the hospital with pancreatitis, and a 5
      cm, distal, pancreatic metastasis was resected. He now has symptomatic paraspinal
      and pleural metastases and is receiving somatostatin. Review of the world's
      literature shows that the majority of patients with thymic carcinoid and MEN-I
      are men with an average age of 37 years. Their clinical course is indolent, and
      surgery represents the only means of cure. Adjuvant chemotherapy and radiation
      therapy confer no survival advantage. The surgical decision making involved in
      treating a patient with thymic carcinoid and hyperparathyroidism associated with
      MEN is also discussed.

PMID- 1352093
TI  - Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis. A risk
      to patients and health care workers.
AB  - OBJECTIVE: To determine the factors associated with the development of multidrug
      resistant tuberculosis among patients at a New York City Hospital and to
      investigate possible nosocomial transmission. DESIGN: A retrospective case
      control study and tuberculin skin test survey. PATIENTS: Twenty-three patients
      with tuberculosis whose isolates were resistant to at least isoniazid and
      rifampin (case patients) were compared with patients with tuberculosis whose
      isolates were susceptible to all agents tested (controls). Tuberculin skin test
      conversion rates were compared among health care workers assigned to wards where
      patients with tuberculosis were frequently or rarely admitted. SETTING: A large,
      teaching hospital in New York City. MEASUREMENTS: Mycobacterium tuberculosis
      isolates from case patients and controls were typed by restriction fragment
      length polymorphism analysis. RESULTS: Case patients were younger (median age, 34
      compared with 42 years; P = 0.006), more likely to be seropositive for HIV (21 of
      23 compared with 11 of 23 patients; odds ratio, 11.5; 95% CI, 1.9 to 117), and
      more likely to have had a previous hospital admission within 7 months before the
      onset of tuberculosis (19 of 23 compared with 5 of 23 patients; odds ratio, 17.1;
      CI, 3.3 to 97), particularly on one ward (12 of 23 compared with 0 of 23
      patients; odds ratio, undefined; P = 0.002). Health care workers assigned to
      wards housing case patients were more likely to have tuberculin skin test
      conversions than were health care workers assigned to other wards (11 of 32
      compared with 1 of 47 health care workers; P less than 0.001). Few (6 of 23) case
      patients were placed in acid-fast bacilli isolation, and no rooms tested had
      negative pressure. Of 16 available multidrug-resistant isolates obtained from
      case patients, 14 had identical banding patterns by restriction fragment length
      polymorphism analysis. In contrast, M. tuberculosis isolates from controls with
      drug-susceptible tuberculosis had patterns distinct from each other and from
      those of case patients. CONCLUSIONS: These data suggest nosocomial transmission
      of multidrug-resistant tuberculosis occurred from patient to patient and from
      patient to health care worker and underscore the need for effective acid-fast
      bacilli isolation facilities and adherence to published infection control
      guidelines in health care institutions.

PMID- 1352094
TI  - Treating sickle cell pain like cancer pain.

PMID- 1352095
TI  - Treating sickle cell pain like cancer pain.

PMID- 1352096
TI  - Plasma endothelin-1 concentrations in polyarteritis nodosa.

PMID- 1352097
TI  - Primary Sjogren's syndrome with antibodies to HTLV-I: clinical and laboratory
      features.
AB  - The prevalence of antibodies to human T lymphotropic virus type I (HTLV-I) was
      studied in patients with primary Sjogren's syndrome. Thirteen of 36 serum samples
      were positive by enzyme linked immunosorbent assay (ELISA) and particle
      agglutination assay for antibodies to HTLV-I and were confirmed by western
      blotting. The presence of antibodies to HTLV-I may signify an HTLV-I carrier
      state. These patients had a high occurrence of extraglandular manifestations such
      as uveitis, myopathy, and recurrent high fever compared with patients who did not
      have antibodies to HTLV-I. Patients with antibodies to HTLV-I had an increased
      spontaneous proliferation of peripheral blood mononuclear cells compared with
      those without the antibodies. The proportions of activated and memory T cells
      (HLA-DR+ CD3+, CD25+ CD3+, and CD29+ CD4+ cells) were higher in HTLV-I carriers
      than in non-carriers. The presence of antibodies to HTLV-I in some patients with
      primary Sjogren's syndrome suggests that HTLV-I may cause primary Sjogren's
      syndrome or its extraglandular manifestations, or both.

PMID- 1352098
TI  - [Neuroleptic malignant syndrome associated with the inadequate antidiuretic
      hormone secretion syndrome].
AB  - Neuroleptic malignant syndrome (NMS) is an adverse reaction of an idiosyncratic
      nature to drugs having antidopaminergic activity. Pathogenesis is largely
      disputed. An NMS case is presented which was triggered by flupentixol and was
      associated with severe hyponatremia (116 mmol/l upon admission). Both clinically
      and analytically, the hyponatraemia fulfills criteria to be considered secondary
      to an inappropriate secretion of antidiuretic hormone (SIADH). Other possible
      causes of hyponatraemia were ruled out. After early treatment with dopaminergic
      agonists and water restriction, both conditions improved in parallel. The
      different pathogenetic possibilities which may explain the temporal coexistence
      of both syndromes in the same patient are discussed. The association of these two
      conditions is in favour of a probable central pathogenetic cause for NMS. On the
      other hand, it is suggested that hyponatraemia may mask the diagnosis of NMS.

PMID- 1352099
TI  - Expression of sialylated Lewis(x) antigen in chronic and neoplastic liver
      diseases.
AB  - Phenotypic expression of sialylated Lewis(x) antigen by means of the monoclonal
      antiserum SNH3 was studied in 87 livers, which included normal and steatotic
      livers and livers with chronic persistent and chronic active hepatitis, alcoholic
      hepatitis, allograft rejection, focal nodular hyperplasia, hepatocellular
      carcinoma, cholangiocarcinoma, metastatic carcinoma, cirrhosis of various causes
      (autoimmune, alcoholic, viral, drug induced, Wilson's disease, and primary
      biliary cirrhosis). The biotin-streptavidin-peroxidase method was used on
      formaldehyde-fixed, paraffin-embedded sections. Sialylated Lewis(x) antigen was
      not demonstrated in normal livers. Hepatocellular expression in a diffuse or
      perinodular honeycomb pattern was seen in cirrhosis, irrespective of cause.
      Sialylated Lewis(x) antigen was also observed in hepatocytes around metastatic
      carcinoma in the absence of inflammation, cirrhosis, or regeneration. Some bile
      ductules, most likely ductular hepatocytes, but not bile ducts, expressed
      sialylated Lewis(x) antigen. Sialylated Lewis(x) antigen was seen diffusely in
      fibrolamellar hepatocellular carcinoma, focally in other hepatocellular
      carcinomas, and either focally or diffusely in cholangiocarcinomas.

PMID- 1352100
TI  - Self-monitoring of panic attacks and retrospective estimates of panic: discordant
      findings.
AB  - An event sampling method was used to study the frequency of panic attacks during
      treatment of agoraphobics. Results revealed a much lower incidence of panic
      attacks in agoraphobics according to self-monitoring than was expected on account
      of their retrospective estimation. When more stringent criteria for panic attacks
      are applied, retrospective overestimation becomes even more apparent. The
      implication of this finding for the classification of panic disorder patients is
      discussed.

PMID- 1352101
TI  - Acute and short-term effects of intraventricular injection of somatostatin and
      LHRH on glutamate and GABA levels in rat brain.
AB  - Glutamate and GABA content in different regions of adult female rat brain were
      determined at 10 and 30 min following intraventricular injection of LHRH or
      somatostatin. Cerebral cortex, cerebellar and hypothalamic glutamate levels were
      significantly elevated at 30 min following injection of 1 micrograms
      somatostatin, whereas hypothalamic glutamate levels were elevated at 10 min
      following a 0.5 micrograms dose. LHRH at a dose of 1 micrograms elevated
      cerebellar and brain stem glutamate levels at 10 and 30 min, whereas a 0.5
      micrograms dose significantly elevated cerebral cortex, cerebellar and
      hypothalamic glutamate levels at 30 min. Third ventricular injection of 1
      micrograms somatostatin produced a significant decrease in hypothalamic GABA
      levels at 10 and 30 min, whereas a 0.5-microgram dose decreased brain stem GABA
      levels at 10 min. LHRH at a dose of 0.1 microgram significantly increased
      cerebral cortex and cerebellar GABA levels at 10 min and brain stem GABA levels
      at 10 and 30 min following injection. Intraventricular injection of LHRH at a
      dose of 0.5 microgram significantly elevated cerebral cortex, cerebellar and
      brain stem GABA levels at 30 min. Hypothalamic GABA levels were elevated at 10
      and 30 min following 0.5 and 1 microgram intraventricular LHRH injection. The
      implications of these results are discussed in relation to probable interaction
      between these neuroactive amino acids and neuropeptides in the rat brain.

PMID- 1352102
TI  - Rapid sequence induction/intubation using intraosseous infusion of vecuronium
      bromide in children.

PMID- 1352103
TI  - The multixenobiotic resistance mechanism in aquatic organisms.
AB  - Many aquatic organisms thrive and reproduce in polluted waters. This fact
      indicates that they are well equipped with a defense system(s) against several
      toxic xenobiotics simultaneously because water pollution is typically caused by a
      mixture of a number of pollutants. We have found that the biochemical mechanism
      underlying such "multixenobiotic" resistance in freshwater and marine mussel, in
      several marine sponges, and in freshwater fish is similar to the mechanism of
      multidrug resistance (MDR) found in tumor cells that became refractory to
      treatment with a variety of chemotherapeutic agents. All these organisms possess
      a verapamil-sensitive potential to bind 2-acetylaminofluorene and vincristine
      onto membrane vesicles. They all express mRNA for mdr1 gene, and mdr1 protein
      product, the glycoprotein P170. Finally, in in vivo experiments, the accumulation
      of xenobiotics is enhanced in all investigated organisms in the presence of
      verapamil, the inhibitor of the P170 extrusion pump. The knowledge that the
      presence of one xenobiotic may block the pumping out, and hence accelerating
      accumulation, of others, may help us to understand and interpret our present and
      past data on different environmental parameters obtained using indicator
      organisms.

PMID- 1352104
TI  - Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5
      blocks acquisition but not expression of fear-potentiated startle to an auditory
      conditioned stimulus.
AB  - The fear-potentiated startle paradigm, in which the amplitude of the startle
      reflex is enhanced in the presence of a stimulus previously paired with
      footshock, was used to measure aversive conditioning after intra-amygdala
      infusion of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist DL-2
      amino-5-phosphonopentanoic acid (AP5). Infusion of 2.5 micrograms/side AP5
      immediately before five noise-footshock pairings on each of 2 consecutive days
      dose-dependently blocked acquisition or consolidation of auditory fear
      potentiated startle, consistent with previous results from our laboratory
      obtained with a visual stimulus. Somatosensory or auditory transmission deficits
      do not appear to be induced by intra-amygdala AP5 because rats reacted normally
      to footshocks and showed reliable potentiated startle expression after pretesting
      AP5 infusion at a dose that blocked acquisition. Together with earlier reports,
      these data suggest that an NMDA-dependent process localized in or near the
      amygdala may be necessary for the acquisition of conditioned fear across
      different sensory modalities.

PMID- 1352105
TI  - Comparative assessment of quantitative HIV viraemia assays.
AB  - OBJECTIVE: To compare two published methods for determining plasma viraemia in
      HIV-seropositive patients, with reference to a cellular viraemia assay. PATIENTS,
      PARTICIPANTS: Three patient groups were defined according to CD4 cell count:
      group I, less than 200 x 10(6)/l (23 patients); group II, 200-500 x 10(6)/l (18
      patients); and group III, greater than 500 x 10(6)/l (13 patients). METHODS: The
      two reported methodologies were applied to all fresh samples, simultaneously and
      on the same day. RESULTS: The two techniques did not differ significantly in the
      detection of plasma viraemia: 82.3% of group I patients and 55% of group II
      patients were positive, while all group III patients were negative. Cellular
      viraemia was positive for 96% of the overall population. CONCLUSIONS: These
      results, obtained in a network of seven French laboratories involved in clinical
      trials, confirm that both plasma viraemia and cellular viraemia are useful
      virological markers.

PMID- 1352106
TI  - Changes in the spectrum of AIDS-defining conditions and decrease in CD4+
      lymphocyte counts at AIDS manifestation in Germany from 1986 to 1991.
AB  - OBJECTIVES: Analysis of changes in the spectrum of AIDS-defining conditions and
      their correlation with CD4+ lymphocyte counts in different risk groups associated
      with HIV transmission. METHODS: Review of data from all adult AIDS cases reported
      in Germany between 1986 and 1991. RESULTS: Among AIDS cases diagnosed between
      1986 and 1991, the proportion of cases with lymphoma and wasting syndrome
      increased, while the proportion of Kaposi's sarcoma decreased. Homosexual men,
      but not intravenous drug users, showed a decrease in the proportion of cases in
      Pneumocystis carinii pneumonia and an increase in the proportions with
      toxoplasmosis and cytomegalovirus infection. The median CD4+ lymphocyte count at
      time of AIDS diagnosis decreased from 73 x 10(6)/l in 1986 (25 and 75
      percentiles, 28 and 212) to 47 x 10(6)/l in 1990 (25 and 75 percentiles, 20 and
      120; P less than 0.01). This decrease was the result of reduced CD4+ lymphocyte
      counts of individuals presenting with opportunistic infections; there was no
      corresponding change for individuals with non-infectious AIDS-defining
      conditions. CONCLUSIONS: AIDS diagnosis is now occurring at a later time in the
      natural history of HIV infection than in 1986, and the relative frequency of
      specific AIDS-defining conditions has changed. Most pronounced is a decrease of
      Pneumocystis carinii pneumonia. Changes in the natural history of HIV infection
      due to therapeutic and prophylactic interventions must be considered when
      interpreting epidemiological data in the course of the AIDS epidemic. These
      changes also have implications for the planning and execution of medical care.

PMID- 1352107
TI  - HIV and HTLV infections in 1305 transfusion-dependent thalassemics in Italy. The
      COOLEYCARE Cooperative Group.
AB  - OBJECTIVE: To evaluate the prevalence of antibodies to HIV-1/2 and HTLV-I/II in
      1305 transfusion-dependent beta-thalassemics treated in 36 centres in Italy.
      DESIGN: Patient serum samples were collected during 1990 and tested in Milan.
      METHODS: Sera were screened using an enzyme-linked immunosorbent assay (ELISA)
      containing viral lysate antigens from HIV-1 and HIV-2, and a particle
      agglutination assay for the detection of antibodies to HTLV-I and HTLV-II.
      Repeatedly reactive samples were examined by Western blot (WB) assays containing
      recombinant and viral lysate antigens. Differential diagnosis was finally made by
      ELISA based on synthetic peptides. RESULTS: Samples from 36 of the 1305 patients
      (2.76%) contained anti-HIV-1 antibodies. In four patients seroconversion occurred
      after the implementation of anti-HIV-1 screening in blood donors in Italy (1985).
      Of the 36 HIV-1-antibody-positive samples, four were HIV-2 [corrected] WB
      indeterminate. These four samples were negative in assays based on specific
      synthetic peptides, suggesting cross-reactivity. Anti-HTLV-I antibodies were
      found in two patients from Sicily and one from Apulia, both southern Italian
      regions. Anti-HTLV-II antibodies were detected in another patient from Sicily.
      CONCLUSIONS: Antibodies to HIV-1, HIV-2, HTLV-I and HTLV-II were detected in
      2.76, 0, 0.23 and 0.08% of patients, respectively. The residual risk of HIV-1
      infection through blood transfusion after the implementation of anti-HIV-1
      screening in blood donors in Italy was approximately 1:50,000 blood units; this
      is based on an approximate number of 200,000 blood units administered to our
      group of patients during 1986-1990 and the occurrence of four new anti-HIV-1
      seroconversions. Seroconversions to HTLV-I/II suggest that these viruses are
      present in Italian blood donors.

PMID- 1352108
TI  - The INVITTOX Data Bank of in-vitro techniques in toxicology.
AB  - The dissemination of information about methods in in-vitro toxicology is subject
      to a number of constraints which are identified and discussed, as are the ways in
      which INVITTOX seeks to address these problems. The continued interest of
      scientists in INVITTOX suggests that a real gap in information provision is being
      filled.

PMID- 1352110
TI  - Differences in the radiotoxicity of two plutonium isotopes in cells in vitro: can
      they be ascribed to different handling by the cells?
AB  - Exposure of Co631 cells to plutonium leads to increasing cell death depending on
      the dose and incubation time. The effects, however, are more pronounced with
      239Pu, than with 238Pu. Uptake and binding of the two radionuclides during a 5-h
      incubation are about equal, but 238Pu is lost more rapidly from the cell. There
      are also differences in the subcellular distribution which lead to a pronounced
      difference in the distribution of radioactivity. The influence of these
      differences in the handling of 238Pu and 239Pu by the cell and of the mass
      difference on the radiotoxicity of the radionuclides is discussed.

PMID- 1352109
TI  - An international appraisal of the minimum duration of chronic animal toxicity
      studies.
AB  - 1. There are international differences in regulatory guidelines for the
      appropriate duration of chronic, two species repeat-dose animal tests for new
      medicines intended for long-term use in man, ranging from 6 months in Europe to
      12 months in Japan and the USA. 2. An adequate data base is necessary to support
      any challenge to the scientific rationale behind regulatory guidelines with
      regard to the design, duration and relevance of toxicity tests of new medicines.
      3. The Centre for Medicines Research has established an international toxicology
      data base which has been expanded to enable a comparison of data obtained within
      6 months, with information from longer periods, for 154 studies. 4. Although new
      findings were revealed after 6 months for 9/75 cases for which pathology data are
      available at 6 and 12 months or longer, and 21/80 with data at 1 or 3 (but not 6
      months) and 12 months or longer, in no instance did these influence the decision
      to drop or further develop the compounds in question. 5. These data suggest that
      a 6-month period of dosing is all that is routinely required for evaluating the
      chronic toxic (excluding carcinogenic) potential of a new chemical entity
      intended for therapeutic use.

PMID- 1352111
TI  - The effect of brassica vegetable consumption on caffeine metabolism in humans.
AB  - Ten healthy volunteers were used in two studies investigating the effect of short
      term Brassica consumption on caffeine metabolism. In the first study volunteers
      were given three Brassica-containing meals, the last one 3 h prior to caffeine
      administration. In the second study volunteers were given two Brassica-containing
      meals and then fasted overnight before caffeine administration. In both studies
      the mean plasma half-life of caffeine was reduced by approximately 20% following
      a Brassica diet, suggesting that Brassica vegetables stimulate caffeine
      metabolism. When caffeine was given 3 h after the last meal, plasma caffeine
      concentrations over 6 h, were increased by up to 27% on the Brassica diet
      compared to controls. This may be due to a transient increased permeability of
      the intestine to caffeine, immediately following Brassica consumption. This
      effect was not seen in the second study where there was a 12-h period between the
      last meal and caffeine administration. There was large interindividual variation
      in the effect of the Brassica diet on caffeine metabolism.

PMID- 1352112
TI  - Acute toxicity in rats of chlorinated hydrocarbons given via the intratracheal
      route.
AB  - 1. The approximate lethal dose (ALD) of six chlorinated hydrocarbons via the
      intratracheal route has been determined in rats and compared with published oral
      LD50 values. 2. The compounds tested in this study were dichloromethane,
      perchloroethylene, trichloroethylene, carbon tetrachloride, chloroform and
      ethylene dichloride. 3. A method of administering the materials intratracheally
      to unanaesthetized animals was developed. 4. The intratracheal ALD of the
      chlorinated hydrocarbons ranged from 3.1 to 17.5% of the oral LD50 and death was
      peracute. 5. Aspiration of chlorinated hydrocarbons may present more of a hazard
      than oral toxicity and should be considered when rendering first aid or emergency
      medical treatment.

PMID- 1352113
TI  - Rat model to investigate the treatment of acute nitrogen dioxide intoxication.
AB  - 1. The pulmonary toxic events induced by acute nitrogen dioxide (NO)2 exposure
      were studied in the rat to develop an inhalation model to investigate therapeutic
      measures. 2. A good correlation was observed between the lung weights and
      severity of the atypical pneumonitis. The pulmonary effects observed, became more
      pronounced with increasing NO2 concentrations (0, 25, 75, 125, 175 or 200 ppm, 1
      ppm NO2 = 1.88 mg m-3 NO2) and exposure times (5, 10, 20 or 30 min). 3. An
      adequate NO2 concentration is 175 ppm, because it can induce a severe lung injury
      without mortality. This makes it possible to investigate suitable therapeutic
      interventions for several days. 4. Following acute inhalatory NO2 intoxication,
      transformation of NO2 to nitrate is presumably more notable than transformation
      to nitrite. 5. The transformation of NO2 to nitrate in lung tissue causes a
      slight increase in the serum nitrite concentration, which does not induce
      measurable formation of methaemoglobin. 6. Presumably, methaemoglobin does not
      contribute to the toxicity of NO2 intoxication.

PMID- 1352114
TI  - Biochemical and histological alterations in rats after acute nitrogen dioxide
      intoxication.
AB  - 1. In previous studies a rat inhalation model was developed to investigate the
      treatment of acute nitrogen dioxide (NO2) intoxication. 2. Biochemical
      parameters, which may be important for the evaluation of lung injury and repair,
      were reviewed and compared with the histology. 3. After exposure to high NO2
      concentrations (75 ppm, 125 ppm or 175 for 10 min) the lung injury observed by
      light microscope was most pronounced after 24 h and became worse with increasing
      concentration. 4. The most sensitive indicators for lung injury in the broncho
      alveolar lavage fluid (BAL) were protein and albumin concentrations, angiotensin
      converting enzyme activity, beta-glucuronidase activity and the presence of
      neutrophil leucocytes. The changes observed in these variables were dose
      dependent. Following exposure to 175 ppm the protein and albumin concentrations
      and the angiotensin converting enzyme activity showed a 100-fold increase, while
      the beta-glucuronidase activity showed a 10-fold increase. 5. Glucose-6-phosphate
      dehydrogenase and glutathione peroxidase in the supernatant of lung homogenate
      and gamma-glutamyl transferase activity in BAL are likely to be the most
      practical parameters for monitoring the phase of repair because their activities
      were maximal at the moment histological changes were reduced in intensity. 6.
      Repair was almost complete 7 d following exposure.

PMID- 1352115
TI  - Elemental mercury vapour toxicity, treatment, and prognosis after acute,
      intensive exposure in chloralkali plant workers. Part I: History,
      neuropsychological findings and chelator effects.
AB  - Mercury poisoning occurred after the acute, prolonged exposure of 53 construction
      workers to elemental mercury. Of those exposed, 26 were evaluated by clinical
      examination and tests of neuropsychological function. Patients received treatment
      with chelation therapy in the first weeks after exposure. Eleven of the patients
      with the highest mercury levels were followed in detail over an extended period.
      Observations included the evaluation of subjective symptoms of distress, using
      the 'Symptom Check List 90-Revised' (SCL-90R) and tests of visual-motor function
      such as 'Trailmaking Parts A and B', 'Finger Tapping', 'Stroop Colour Word Test'
      and 'Grooved Pegboard.' On day 85 +/- 11 (mean +/- s.d.) after exposure, these 11
      men again received either 2,3-dimercaptosuccinic acid (DMSA) or N-acetyl-D, L
      penicillamine (NAP) in a short-term study designed to compare the potential to
      mobilize mercury and the incidence of drug-induced toxicity of these two
      chelating agents. Rapidly resolving metal fume fever was the earliest
      manifestation of symptoms. CNS symptoms and abnormal performance on
      neuropsychological tests persisted over the prolonged period of follow-up. There
      were significant correlations between neuropsychological tests and indices of
      mercury exposure. Serial mercury in the blood and urine verified the long half
      life and large volume of distribution of mercury. Chelation therapy with both
      drugs resulted in the mobilization of a small fraction of the total estimated
      body mercury. However, DMSA was able to increase the excretion of mercury to a
      greater extent than NAP. These observations demonstrate that acute exposure to
      elemental mercury and its vapour induces acute, inorganic mercury toxicity and
      causes long-term, probably irreversible, neurological sequelae.

PMID- 1352116
TI  - Elemental mercury vapour toxicity, treatment, and prognosis after acute,
      intensive exposure in chloralkali plant workers. Part II: Hyperchloraemia and
      genitourinary symptoms.
AB  - Exposure to elemental mercury vapour is known to influence renal function;
      however, severe renal disease has not been consistently identified. Eleven men
      were evaluated for renal disease after acute, massive mercury poisoning.
      Significant hyperchloraemia was identified in this group of patient and a
      reversible renal tubular defect was suggested by low normal serum bicarbonate, a
      normal serum anion gap and a positive urinary anion gap. The only other evidence
      of renal dysfunction was transient, mild proteinuria in one of the 11 patients.
      During this same time period, neuropsychological impairment was identified on a
      test of cognitive and visual-motor function, 'Trailmaking B', in seven of the 11
      patients. Additionally, dysuria and ejaculatory pain occurred without evidence of
      urological disease. These complaints were more frequent in those patients with
      impairment on 'Trailmaking B' suggesting a neurological basis for these symptoms.
      The findings of this study support earlier observations that the brain rather
      than the kidney is the critical target organ after elemental mercury vapour
      exposure.

PMID- 1352117
TI  - Changes in antioxidant lung protection after single intra-tracheal cadmium
      acetate instillation in rats.
AB  - One-hundred male white rats were given a single intratracheal dose of 0, 5 mg kg
      1 cadmium acetate. There was a fall in catalase (CAT) and superoxide dismutase
      (SOD) in lung homogenate throughout the 30 d after treatment. Non-protein
      sulphhydryl (NPSH) content, glucose-6-phosphate dehydrogenase (G-6-PD) and
      glutathione peroxidase (GP) were all increased from days 5 to 15. There was an
      increase in lactate dehydrogenase (LDH) and protein in bronchoalveolar lavage
      fluid (BALF) and in the relative weight of the lungs which provide evidence of
      severe toxic lesions of the lungs. Increased lipid peroxidation provoked by the
      reduced lung antioxidant protective capacity may be an important mechanism in the
      pulmonary damage caused by cadmium.

PMID- 1352119
TI  - Biological and biological-effect monitoring of workers exposed to 4,4'-methylene
      bis(2-chloroaniline).
AB  - 4,4'-Methylene-bis(2-chloroaniline) (MOCA), a curing agent used in polyurethane
      manufacture, is a genotoxic and carcinogenic amine. This study aimed to assess
      occupational exposure to MOCA using as indices: (1) the post-work urinary output
      of MOCA; (2) urinary thioethers, assuming that conjugation with glutathione might
      be a significant pathway for the elimination of putative electrophilic
      metabolites of MOCA; and (3) sister-chromatid exchange (SCE) frequency in
      peripheral lymphocytes as an indicator of genetic damage. Process workers at a
      polyurethane production unit were found to have up to 38 mumol MOCA mol-1
      creatinine in their urine at the end of a work shift. Smaller quantities were
      found in the urine of laboratory and supervisory staff, but none was detected in
      the urine of a group of office and sales staff from an unrelated industry, who
      served as unexposed controls. There was no evidence of MOCA-related urinary
      thioether output. There was a graded increase in SCE frequency from controls to
      process workers, consistent with their apparent exposure to MOCA. Administration
      of MOCA to rats (5 daily i.p. injections of 125 or 250 mg kg-1 resulted in dose
      related increases in MOCA excretion and in lymphocyte SCE frequency, but there
      was no change in thioether output. These results indicate that urinary thioether
      excretion is inappropriate for monitoring MOCA exposure, but that where MOCA
      exposure can be demonstrated, by the presence of MOCA in urine, this is
      associated with genetic damage in both man and in the rat.

PMID- 1352118
TI  - The interactive effect of chlorine, copper and nitrite on methaemoglobin
      formation in red blood cells of Dorset sheep.
AB  - Simultaneous exposure to chemicals which can oxidize the haemoglobin of the red
      blood cell to methaemoglobin is common. Although the effects of some of these
      agents have been documented individually, little research considers the
      interactive effects. In-vitro experiments on the treated blood of female Dorset
      sheep assessed the interactive capacity of chlorite, copper and nitrite to affect
      methaemoglobin formation. All combinations of doses which produced 2.5, 5, 10%
      methaemoglobin were tested in all possible combinations (a total of 80), as were
      the controls. This included data on each chemical alone, each two-way combination
      and the three-way combination. The response is largely additive (the sum of the
      individual effects) except for one of the two-way interactions, chlorite/nitrite
      (P less than .01), which showed antagonism. Chlorite may oxidize nitrite which
      could explain the less-than-additive response. Overall, the result of combining
      these agents on methaemoglobin was additive.

PMID- 1352120
TI  - Alcohol in cerebrospinal fluid (CSF) and alcoholism.
AB  - Alcohol levels were measured in 15 cerebrospinal fluid (CSF) samples and 14 blood
      samples from grade III and IV male alcoholic patients with signs of nervous
      system involvement, and compared with levels detected in 11 CSF samples and 11
      blood samples from abstemious patients or patients with grade I or II alcoholism
      whose CSF had been found to be normal by routine analysis (controls). Among the
      alcoholic patients, alcohol levels were lower in the CSF than in blood, whereas
      the opposite was true for the controls. The possible mechanisms underlying this
      difference are discussed and the need for further study of this topic is
      emphasized.

PMID- 1352121
TI  - ICCCR International Conference on Cancer Prevention: Facts, Maybes and Rumors.
      Bethesda, Maryland, February 12-13, 1991.

PMID- 1352122
TI  - Plasma determination of the enantiomers of SL 84.0418, a new antihyperglycaemic
      drug, by HPLC on a chiral alpha 1-AGP column.
AB  - SL 84.0418 is a new antihyperglycaemic drug. It is an orally active and selective
      alpha 2-adrenoceptor antagonist. This molecule, a pyrroloindole derivative,
      contains an asymmetric center yielding two enantiomers. In order to evaluate the
      pharmacokinetic profile of both enantiomers following oral administration of the
      racemate we have developed an HPLC method for their separation and
      quantification. The liquid-liquid extraction involved three steps with two
      salting-out procedures at pH 11.5 before and after a back-extraction with 0.005 M
      H2SO4. The enantiomers were separated by HPLC on a stainless-steel column (100 x
      4.0 mm) packed with a chiral alpha 1-acid. The UV response was linear from 1 to
      250 ng/ml for both enantiomers. The relative standard deviation (RSD) for
      reproducibility was below 10.7%. Using quality control samples, precision was
      found below 7.8% and accuracy was 108%. Extraction recoveries were ca. 60% for
      both enantiomers and 94% for the internal standard. Column life was brought up to
      2 months, which corresponds to about 1,000 injections of biological extract. No
      guard column was used, but a daily back-flush was carried out. This method is
      suitable for routine analysis and 30 to 40 plasma samples a day can be processed.
      This method allows the definition of the pharmacokinetic profile of both
      enantiomers of SL 84.0418 in human plasma after single oral administration of
      doses as low as 20 mg of the racemic drug.

PMID- 1352123
TI  - Crescentic glomerulonephritis in children.
AB  - Data on patients with crescentic glomerulonephritis (greater than 50% glomeruli
      with crescents), referred to the Hospital for Sick Children during the past 13
      years, were reviewed. Thirty patients (13 male, 17 female) aged 3.7-15.7 years
      (mean 9.5) were evaluated. Initial clinical features included: oedema (24/30),
      hypertension (19/30), gross haematuria (15/30), oliguria (15/30) and a decreased
      glomerular filtration rate (GFR less than 30 ml/min per 1.73 m2) (22/30). Henoch
      Schonlein purpura was present in 9 patients, microscopic polyarteritis in 3,
      polyarteritis nodosa in 1, Wegener's granulomatosis in 1, systemic lupus
      erythematosus in 1, post-streptococcal glomerulonephritis in 2, mesangiocapillary
      glomerulonephritis in 7, anti-glomerular basement membrane glomerulonephritis in
      2, and 4 were idiopathic. In 10 patients 50%-79% of glomeruli were affected by
      crescentic changes (group 1) and in the remaining 20, 80% or more (group 2). The
      crescents were cellular, fibrocellular or fibrous, and the degree of sclerosis
      was assessed. Patients in both groups were treated with plasma exchange,
      corticosteroids, anticoagulants, cyclophosphamide and azathioprine in different
      combinations. On follow-up, 3 patients were dead, 1 was lost to follow-up, 12
      were on dialysis/transplant programmes, 4 had a GFR of less than 30 and 10 a GFR
      of more than 30 ml/min per 1.73 m2. In our experience, 50% progressed to end
      stage renal failure. The interval between disease onset and start of treatment
      was a prognostic factor for outcome. Fibrous crescents were associated with a
      worse outcome than fibrocellular crescents (P less than 0.05). Outcome was not,
      however, related to the percentage of glomeruli affected (P greater than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352124
TI  - Loss of heterozygosity on chromosomes 1 and 11 in carcinoma of the pancreas.
AB  - Little is known of the molecular-genetic changes in carcinoma of the pancreas
      (CaP). In order to investigate the allele loss, or loss of heterozygosity (LOH),
      in CaP, we studied 13 patients with exocrine CaP and two with endocrine CaP using
      restriction fragment length polymorphism analysis. Twenty probes assigned to
      chromosomes 1, 5, 7, 9, 11, 12, 13, 14, 16, 17 and 18 were used. The frequency of
      LOH, or fractional allele loss (FAL), was found in two endocrine tumours to be
      0.333 and 0.455 respectively; and FAL in 13 oxocrine tumours ranged from 0 to
      0.25. Allele loss was shown in both exocrine and endocrine tumours by the probes
      Lambda MS1 at 1p33-35, and pMS51 at 11q13. Probes for other chromosomes have as
      yet shown no consistent LOH. In conclusion, the study showed LOH on chromosomes 1
      and 11 in both exocrine and endocrine CaP.

PMID- 1352126
TI  - Somatostatin in the treatment of paraneoplastic diarrhoea in patients with small
      cell lung cancer.

PMID- 1352125
TI  - Expression of c-erbB-2 protein in papillary thyroid carcinomas.
AB  - c-erbB-2 protein expression was investigated immunohistochemically in frozen
      thyroid tissue specimens from 42 patients using a polyclonal sheep antibody. c
      erbB-2 immunoreactivity was detected in 12 out of 17 papillary carcinomas, while
      no c-erbB-2 protein immunostaining was seen in cases of follicular adenoma (five
      cases), follicular carcinoma (five cases) or medullary carcinoma (one case), nor
      in cases of non-neoplastic tissue, including normal thyroid tissue from tumour
      bearing glands. RNA was extracted from 51 thyroid tissue samples from 34 of the
      above patients, and c-erbB-2 mRNA was analysed by slot-blot hybridisation. c-erbB
      2 mRNA was detectable in all samples, but papillary carcinomas and lymph node
      metastases showed significantly higher levels of c-erbB-2 mRNA compared to non
      neoplastic tissue. The present demonstration of positive c-erbB-2 immunostaining
      in papillary thyroid carcinomas is contradictory to previous findings on formalin
      fixed, paraffin-embedded material, and emphasises the importance of tissue
      quality for c-erbB-2 protein detection.

PMID- 1352127
TI  - Analysis of J beta gene segment usage by CD4+ and CD8+ human peripheral blood T
      lymphocytes.
AB  - Certain T cell antigen receptor V gene products in man have been shown by us and
      others to display a reproducible bias for preferential expression in CD4+ or CD8+
      T cell subsets. In order to investigate whether such a skewed representation of V
      gene segments is also present at the J gene segment level, we tested the relative
      J beta gene usage by V beta 5.1 + T cells, as this V beta gene is biased towards
      CD4+ T cell expression in virtually all individuals. To analyze the usage of the
      13 J beta gene segments, we developed a new approach using V beta 5.1 and C beta
      specific oligonucleotides as 5' and 3' primers respectively for polymerase chain
      reaction (PCR) amplification of cDNA derived from CD4+ or CD8+ peripheral blood
      lymphocyte (PBL) T cells. The PCR products were visualized for reactivity with
      individual J beta 1.1-1.6 and J beta 2.1-2.7 32P-labelled oligonucleotide probes
      using autoradiography and quantitative gel-scanning. Eleven normal blood donors
      provided the PBL T cells. The results showed that in every individual's V beta
      5.1+ T cell populations (CD4 and CD8), all V beta/J beta combinations were used
      although at varying but reproducible levels for each J beta gene. Thus, no
      discernible disallowance of combinations existed. Moreover, we could show that
      six of 13 J beta genes were unequally expressed when compared in pairs with
      regard to expression in CD4+ and CD8+ T cell subsets.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1352128
TI  - The thymic compartment responsible for positive selection of CD4+ T cells.
AB  - Our aim was to assess the generality of the observation that positive selection
      of CD4+ T cells is mediated by MHC class II molecules on epithelial cells of the
      thymic cortex. By appropriate matings of previously established transgenic and
      mutant mouse lines, we were able to produce animals that lacked MHC class II
      molecules; individuals expressing only the class II E complex, but in all the
      usual thymic compartments; animals that had E molecules in the thymic medulla but
      not in the cortex; and, reciprocally, individuals expressing the E complex in the
      thymic cortex but essentially not in the medulla. Those mice which displayed
      class II molecules in the cortex had normal numbers of CD4+CD8- T cells in the
      thymus and CD4+ T cells in the periphery, while 'bare' cortex mice were almost
      devoid of mature CD4 single positive cells. This finding serves to generalize
      observations from previous studies of similar design but limited to assaying
      positive selection of T cells which expressed a single transgenic E-restricted
      TCR or a subset of V beta 6+ TCRs.

PMID- 1352129
TI  - Specific drug binding by purified lipid-reconstituted P-glycoprotein: dependence
      on the lipid composition.
AB  - We fused P-glycoprotein with beta-galactosidase at the C-terminus aiming to study
      the mechanism of drug binding of P-glycoprotein in reconstitution experiments.
      Expression of the fusion protein in NIH 3T3 cells conferred a multidrug-resistant
      phenotype, suggesting that beta-galactosidase fusion at the C-terminus does not
      affect the functions of P-glycoprotein. The fusion protein was partially purified
      by simple immunoprecipitation with anti-beta-galactosidase polyclonal antibody,
      and its [3H]azidopine binding property was investigated in the presence of
      various compositions of liposomes. The purified P-glycoprotein, after
      reconstitution into liposomes, was capable of binding [3H]azidopine. When the
      cholesterol content of liposomes was increased to a weight ratio of 20%, the
      specific binding activity of the partially purified fusion protein was
      stimulated, and when the cholesterol content was increased higher, the binding
      activity decreased. The binding was specifically decreased by competition with
      vinblastine. Stigmasterol was less effective, and ergosterol was the least
      effective in stimulating the specific binding.

PMID- 1352130
TI  - In vivo and in vitro induction of 'tissue' transglutaminase in rat hepatocytes by
      retinoic acid.
AB  - Tissue transglutaminase (tTG) expression was found to be induced in rat liver
      following in vivo retinoic acid (RA) treatment (Piacentini et al. (1988) Biochem.
      J. 253, 33-38). Here we show that the increased enzyme expression in rat liver is
      at least partially the result of the action of RA in parenchymal cells. In fact,
      (a) when hepatocytes are isolated from RA-treated animals their transglutaminase
      protein content is much higher than in similarly isolated control cells; (b)
      higher tTG protein level is also found by immunoelectronmicroscopy in the
      hepatocytes of the RA-treated rats as compared with the very low amount detected
      in the controls; (c) RA induces tTG in hepatocytes under culture conditions as
      well. One of the functions of tTG is to form a protein polymer in dying apoptotic
      cells by epsilon(gamma-glutamyl)lysine and, specifically gamma-glutamylpolyamine
      cross-links (Fesus et al. (1989) FEBS Lett. 245, 150-154). Noteworthy, after in
      vivo and in vitro RA-treatment we could not determine any increase (there was
      even a slight decrease) in the number of the cross-linked apoptotic envelopes. In
      keeping with this is the significant reduction of protein bound gamma
      glutamylpolyamine detected in hepatocytes exposed to RA in culture. These
      findings suggest that the RA-induced tTG in parenchimal cells is an inactive
      form.

PMID- 1352131
TI  - Biotinylated peptides containing a factor XIIIa or a tissue transglutaminase
      reactive glutaminyl residue that block protein cross-linking phenomena by
      becoming incorporated into amine donor sites.
AB  - Biotinylated peptides Biot-Gln-Gln-Ile-Val and Biot-epsilon-Aca-Gln-Gln-Ile-Val
      were shown to act as acceptor substrates for amines in reactions catalyzed by
      both tissue transglutaminase and coagulation factor XIIIa. Moreover, the peptides
      could be employed for specifically blocking the potential amine donor sites of
      protein substrates participating in biological cross-linking with these enzymes.
      The presence of the biotin label allowed for ready detectability of the marked
      donor substrates during the cross-linking of crystallins in lens homogenate by
      the intrinsic transglutaminase and that of the alpha chains of human fibrin by
      factor XIIIa.

PMID- 1352132
TI  - Morphology, DNA ploidy and allele losses on chromosome 11 in sporadic
      hyperparathyroidism and that associated with multiple neoplasia, type 1.
AB  - OBJECTIVE: To analyse different forms of hyperparathyroidism (for example,
      sporadic and multiple endocrine neoplasia type 1 (MEN 1)) by histopathology, DNA
      cytometry and by the presence of allele losses on chromosome 11, thereby
      identifying common characteristics. MATERIAL: Enlarged glands from 26 patients
      with hyperparathyroidism (23 sporadic and 3 MEN 1). Cytometric assessment was
      made of 28 glands. RESULTS: Nine patients had multiple gland disease and 15 had
      single gland disease (14 sporadic and 1 MEN 1). DNA cytometry showed that 18 (15
      sporadic and all 3 MEN 1) were diploid, seven tetraploid, and two aneuploid. Two
      glands from one sporadic case showed different ploidy patterns. Seven patients
      with sporadic and all three with MEN 1 hyperparathyroidism had allele losses for
      chromosome 11 in the analysed glands. CONCLUSION: There were no significant
      differences in histopathological appearances, ploidy, or allele losses among
      abnormal glands from a variety of forms of hyperparathyroidism.

PMID- 1352134
TI  - The possible role of Chlamydia trachomatis in perineal suppurative hidradenitis.
AB  - OBJECTIVE: To find out if there is an association between perineal suppurative
      hidradenitis and Chlamydia trachomatis infection. DESIGN: Open study. SUBJECTS:
      Seven consecutive patients treated for perineal suppurative hidradenitis during
      the past three years, and 10 control subjects who were being treated for acute
      cryptogenic perianal abscesses. MAIN OUTCOME MEASURE: Presence of C. trachomatis
      detected by direct immunofluorescent staining. RESULTS: All but one patient had
      serological evidence of C. trachomatis infection. All 10 control subjects failed
      to react to IgA antibodies to C. trachomatis, and two reacted to IgG antibodies.
      CONCLUSION: There may be a link between C. trachomatis infection and suppurative
      hidradenitis, but it is uncertain whether it is a direct cause or a predisposing
      factor.

PMID- 1352133
TI  - Hyperparathyroidism associated with treatment of manic-depressive disorders by
      lithium.
AB  - OBJECTIVE: To clarify the association between treatment of affective psychiatric
      disorders with lithium, and the development of secondary hyperparathyroidism.
      DESIGN: Retrospective review of medical records, 1973-89. SUBJECTS: 17 patients
      with affective psychiatric disorders who were treated with lithium (n = 6) or
      with tricyclic antidepressant, or neuroleptic, drugs (n = 11) all of whom were
      operated on for hyperparathyroidism. MAIN OUTCOME MEASURE: Duration of lithium
      therapy and parathyroid histology. RESULTS: Parathyroid hyperplasia was present
      in 5 patients who had taken lithium during a median period of 13 years. A
      parathyroid adenoma was found in one patient treated with lithium for three
      years. Ten of the 11 patients who had been treated with tricyclic antidepressant,
      or neuroleptic drugs had a parathyroid adenoma and the remaining one had an
      adenoma as an underlying cause of hyperparathyroidism. CONCLUSION:
      Hyperparathyroidism in patients who have undergone long term treatment with
      lithium is associated with parathyroid hyperplasia. This indicates that lithium
      may exert a chronic stimulus that results in secondary hyperparathyroidism.

PMID- 1352135
TI  - Risk factors in perforated peptic ulcer disease: comparison of a new score system
      with the Mannheim Peritonitis Index.
AB  - OBJECTIVE: To construct a score that would accurately predict outcome for
      patients with perforated peptic ulcers. DESIGN: Retrospective study. SETTING:
      University Hospital. SUBJECTS: 173 patients who were operated on for perforated
      peptic duodenal ulcers over a 14 year period. MAIN OUTCOME MEASURES: Results of
      multivariate discriminant function analysis of derived set of clinical variables
      known to be associated with high mortality, and comparison with the Mannheim
      Peritonitis Index. RESULTS: Serious coexisting medical illness, acute renal
      failure, white cell count of more than 20 x 10(9)/l, and male sex were the most
      significant factors influencing mortality. The Hacettepe score for perforated
      peptic ulcer was established using these four variables. The sensitivity was 83%,
      the specificity 94%, and the overall predictive accuracy 93%. The corresponding
      figures for the Mannheim Peritonitis Index were 75%, 96%, and 94% respectively.
      CONCLUSION: The Hacettepe score is useful in predicting whether a patient will
      survive after perforation of a peptic duodenal ulcer.

PMID- 1352137
TI  - Accurate diagnosis of acute appendicitis: a retrospective and prospective
      analysis of 686 patients.
AB  - OBJECTIVE: To formulate a score system that would make the preoperative diagnosis
      of acute appendicitis more accurate. DESIGN: Retrospective then prospective
      study. SETTING: City University Hospital. SUBJECTS: 536 patients who had their
      appendixes removed between 1981 and 1986 (retrospective study), and 150
      consecutive patients admitted with a presumptive diagnosis of appendicitis
      between 1987 and 1988 (prospective study). MAIN OUTCOME MEASURES: Correlation
      between the histological diagnosis of appendicitis and variables representing
      history, clinical examination, and laboratory investigations. RESULTS: The rate
      of histologically proven negative appendicectomies in the retrospective series
      was 40% and in the prospective series 33%. The variables that were thought to be
      predictive were: male sex, white cell count of greater than 11 x 10(9)/l, history
      of less than 24 hours with no previous complaints, rebound tenderness, shift of
      pain from the epigastrium, and localised guarding, but all criteria had low
      specificities and sensitivities when applied prospectively, and combining the
      scores did not improve them. CONCLUSION: The accurate diagnosis of appendicitis
      depends largely on the experience of the surgeon and is not improved by the
      application of a score system that includes the above variables.

PMID- 1352136
TI  - Effect of proximal gastric vagotomy on the activity of hydrogen, potassium
      stimulated ATPase in the gastric mucosa of patients with duodenal ulcer.
AB  - OBJECTIVE: To find out if there was a correlation between hydrogen, potassium
      stimulated ATPase (H,K-ATPase) activity and gastric acid secretion in patients
      with duodenal ulcers after proximal gastric vagotomy. DESIGN: Retrospective
      study. SETTING: Regional referral center. SUBJECTS: 61 patients with chronic
      duodenal ulcers divided into three groups: patients who had not been operated on
      but had exacerbations of their symptoms (n = 39): those who had been treated
      successfully by proximal gastric vagotomy either less than 1 year ago (n = 7) or
      greater than or equal to 1 year ago (n = 9): and those patients who presented
      with recurrent ulceration after proximal gastric vagotomy (n = 6). MAIN OUTCOME
      MEASURES: Measurement of H,K-ATPase activity and gastric acid secretion. RESULTS:
      There was a decrease in H,K-ATPase activity after effective vagotomy, and enzyme
      activity was the lowest in patients who had been operated on 1 year ago. Both H,K
      ATPase and gastric acid secretion were decreased by proximal gastric vagotomy.
      CONCLUSION: There may be a gradual recovery of gastric H,K-ATPase activity with
      time after proximal gastric vagotomy.

PMID- 1352138
TI  - Patterns of propulsive motility in the human colon after abdominal operations.
AB  - Twenty patients about to undergo elective cholecystectomy who were not using
      laxatives or drugs known to affect gastrointestinal motility and who did not give
      a history of gastrointestinal disease were investigated in a prospective open
      study. Patients swallowed two capsules each containing four radio-opaque markers
      every 12 hours starting 48 hours before operation. The pattern of resolution of
      postoperative colonic paralysis was monitored by serial abdominal radiographs
      taken every 12 hours until motility had returned to the rectum/sigmoid colon. In
      all 17 patients who completed the study propulsive motility started significantly
      earlier in the right colon (mean 61 hours) than in any other part (p less than
      0.01). The gradient of resolution of postoperative colonic paralysis was always
      from proximal to distal, adding to the accumulating body of experimental evidence
      that implicates the right colon to return to normal first.

PMID- 1352140
TI  - Gracilis muscle transposition for sexual dysfunction after proctectomy.

PMID- 1352139
TI  - Association of ploidy and cell proliferation, Dukes' classification, and
      histopathological differentiation in adenocarcinomas of colon and rectum.
AB  - OBJECTIVES: To find out if there is an association between DNA indexes and DNA
      synthesis (S) phase measurements and Dukes' classification and histopathological
      differentiation in colorectal cancers, and to investigate the interrelationship
      between DNA indexes and S phase measurements. DESIGN: Prospective open study.
      MATERIAL: 182 colorectal carcinomas in 181 consecutive patients. INTERVENTION:
      Tumours biopsied immediately after resection or at rectoscopy or colonoscopy.
      RESULTS: One or more aneuploid cell populations were found in 113 of 182
      carcinomas (62%). There was no correlation between Dukes' stage and either degree
      of differentiation or S phase measurements, but there were significant
      correlations between S phase measurements and histological grading (p less than
      0.05), and between the percentage of cells in the S phase and the DNA index when
      values for both diploid and aneuploid tumours were included (p less than 0.001).
      CONCLUSION: The degree of aneuploidy indicates how far tumour cells have
      progressed in their cellular disarrangement, and information about a tumour's
      proliferative capacity is given by the S phase measurements.

PMID- 1352141
TI  - Acral lentiginous melanoma in situ.
AB  - Acral lentiginous melanoma in situ is a rare entity in the broad spectrum of
      melanoma. Although acral lentiginous melanoma is not uncommon, the in situ
      variant seems to have been reported only twice in the literature. An additional
      case is described.

PMID- 1352142
TI  - Traumatic cholecystectomy.
AB  - Avulsion of the gallbladder from its liver bed with detachment from both cystic
      duct and artery is an exceedingly rare consequence of blunt abdominal injury. A
      case is reported in which early recognition by diagnostic peritoneal lavage led
      to successful treatment.

PMID- 1352143
TI  - Acalculous Candida cholecystitis.

PMID- 1352144
TI  - Juxta-anastomotic sacciform dilation: an unusual complication of colonic stapled
      suture.
AB  - The commonest complications of stapling closure in gastrointestinal surgery are
      dehiscence, bleeding at the site of anastomosis and stenosis. Juxta-anastomotic
      sacciform dilation following end-to-side circular stapling anastomosis of the
      left colon is reported as an unusual complication. The case highlights the need
      for careful technique in order to obtain all the advantages offered by staplers.

PMID- 1352145
TI  - Pancreatic pseudocyst causing spontaneous gastric haemorrhage.

PMID- 1352146
TI  - Human endometrial stromal cells and decidual cells express cluster of
      differentiation (CD) 13 antigen/aminopeptidase N and CD10 antigen/neutral
      endopeptidase.
AB  - With specific monoclonal antibodies, we found that human endometrial stromal
      cells and decidual cells express two function-related surface antigens. Indirect
      immunofluorescence staining revealed that both endometrial stromal cells and
      decidual cells during the first trimester of pregnancy expressed cluster of
      differentiation (CD) 13 antigen and CD10 antigen, which are identical to
      aminopeptidase N and neutral endopeptidase, respectively. By flow cytometric
      analysis, CD13 antigen was detected on 82-93% of the examined cells, and CD10
      antigen was detected on 75-93% of the examined cells in endometrial stromal cell
      enriched preparations. Furthermore, peptidase activity was detected in these cell
      preparations by an assay based on the hydrolysis of alanine-p-nitroanilide into p
      nitroaniline and alanine.

PMID- 1352148
TI  - Role of the sympathetic innervation on uterine electromyographic activity in
      nonpregnant ovariectomized sheep under estrogen supplementation.
AB  - The aims of the present study were to characterize the sympathetic innervation of
      the nonpregnant sheep uterus, to determine the catecholamine content in
      myometrium (MYO) and endometrium, and to study the effects of chemical
      sympathectomy (CHSPX) on uterine catecholamine content and on uterine
      electromyographic (EMG) activity recorded from the MYO and mesometrium (MESO) in
      the nonpregnant ovariectomized sheep. After synchronization of estrus, 9
      nonpregnant sheep were anesthetized with halothane, ovariectomized, and fitted
      with vascular catheters and EMG electrodes. Estradiol-17 beta was administered
      intravascularly at a rate of 50 micrograms/24 h for 10 days. CHSPX was induced
      with 6-hydroxy dopamine (20 mg/kg). Uterine tissues were obtained for
      determination of catecholamine content by HPLC and for immunocytochemical
      staining using an antibody against tyrosine hydroxylase (TH). In nonpregnant
      ovariectomized sheep, TH immunostaining was present in nerve fibers located in
      endometrium and MYO. In all layers of the uterus, catecholamine fibers were found
      in the proximity of blood vessels as well as in defined regions of the
      parenchyma. Throughout the uterus, norepinephrine content and TH immunostaining
      were dramatically decreased after CHSPX. CHSPX decreased uterine short EMG event
      activity in both MYO and MESO. Contracture-type activity was not affected in MYO
      and was increased in MESO. We conclude that sympathetic innervation modulates the
      MYO and MESO EMG activity in nonpregnant ovariectomized sheep under estradiol
      supplementation, and that the removal of the sympathetic innervation induces a
      decrease in the spontaneous activity.

PMID- 1352147
TI  - Characterization of rabbit testis beta-galactosidase and arylsulfatase A:
      purification and localization in spermatozoa during the acrosome reaction.
AB  - Examination of the role of carbohydrates in specific recognition between
      spermatozoa and zona pellucida has focussed on understanding the interaction of
      sperm hydrolases or lectin-like molecules with zona pellucida ligands. To
      elucidate the role of specific spermatozoan hydrolases in gamete interaction,
      rabbit testis beta-galactosidase and arylsulfatase A were purified,
      characterized, and localized in spermatozoa. beta-Galactosidase and arylsulfatase
      A co-purified after affinity, size, or reverse-phase chromatography. N-Terminal
      amino acid analysis and enzymatic characterization suggested that neither enzyme
      is a testis-specific isozyme. Size chromatography indicated that both enzymes
      aggregated into macromolecular complexes at pH 4.0, while both dissociated at pH
      8.0. beta-Galactosidase and arylsulfatase A co-localized on the sperm surface and
      in the acrosome and postacrosomal regions of spermatozoa. Throughout the zona
      induced acrosome reaction, both enzymes remained associated with the detached
      acrosomal cap and postacrosomal region of acrosome-reacted spermatozoa. Because
      the acrosome is an acidic subcellular compartment, internal beta-galactosidase
      and arylsulfatase A are probably aggregated in acrosome-intact spermatozoa and
      dissociate as they are exposed to pH increases during the acrosome reaction.

PMID- 1352149
TI  - Evaluation of new oral antimicrobial agents and the experience with cefprozil--a
      broad spectrum oral cephalosporin. Symposium. Amelia Island, Florida, 26-29
      September 1991.

PMID- 1352150
TI  - Molecular analysis provides evidence for the endogenous origin of bacteremia and
      meningitis due to Enterobacter cloacae in an infant.
AB  - We analyzed the restriction fragment length polymorphism (RFLP) of total DNA and
      of ribosomal DNA regions (ribotyping) to document the occurrence of endogenous,
      systemic bacteremia and meningitis due to Enterobacter cloacae in a newborn. Five
      strains of E. cloacae were isolated from this newborn. Three of these strains
      were recovered from stool at counts of 10(8), 10(9), and 10(9) organisms/g of
      feces, respectively; one strain was isolated from blood; and one strain was
      isolated from cerebrospinal fluid. In addition, five epidemiologically unrelated
      strains of E. cloacae were studied for comparison. Our study clearly shows the
      genetic relatedness of the strains isolated sequentially from cultures of stool,
      blood, and cerebrospinal fluid. RFLP analysis of total DNA and ribotyping seem
      particularly well suited to the study of the epidemiology of nosocomial E.
      cloacae strains.

PMID- 1352151
TI  - [New perspectives. Pharmacological approach to arterial hypertension].

PMID- 1352152
TI  - The effect of cytokines on the expression of MHC antigens and ICAM-1 by normal
      and transformed synoviocytes.
AB  - We report the expression on synovial cells of cell surface molecules known to be
      involved in T cell activation by antigen presenting cells. Normal human synovial
      fibroblasts and a human synovial cell line transformed with the SV40 large T
      antigen were used for in vitro stimulation studies with recombinant cytokines. We
      demonstrate an increase in MHC-A, B, C expression in normal synovial cells in
      response to recombinant interferon gamma (r gamma IFN), tumour necrosis factor
      alpha and beta (rTNF alpha and beta) and interleukin-1 (rIL-1 alpha).
      Intercellular adhesion molecular-1 (ICAM-1) expression was increased in parallel
      with MHC Class I. The combination of r gamma IFN and rTNF alpha was additive in
      its effect on ICAM-1 expression. Northern blot analysis suggests that ICAM-1
      expression in synovial cells is controlled at the level of transcription. In
      contrast, MHC Class II (HLA-DR) was only significantly induced by r gamma IFN.
      Other stimuli including interleukin-4 (IL-4), interleukin 6 (IL-6), granulocyte
      macrophage colony stimulating factor (GM-CSF) and prostaglandin E2 (PGE2) did not
      affect the expression of ICAM-1 or MHC Class I and II. Leucocyte function antigen
      3 (LFA-3) expression was not affected by any of the stimuli tested.
      Immunoperoxidase staining of rheumatoid synovial tissue confirmed enhanced in
      vivo expression of ICAM-1 in rheumatoid arthritis. These changes are discussed in
      the context of T cell activation in inflammatory arthritis.

PMID- 1352153
TI  - T cell receptor beta gene polymorphism and rheumatoid arthritis.
AB  - Susceptibility to rheumatoid arthritis is, in part, conferred by genetic factors.
      Previous studies have suggested that inheritance of a particular allele of a
      restriction fragment length polymorphism (RFLP) detected in the T cell receptor
      beta (TCR beta) gene complex is associated with rheumatoid arthritis (RA). We
      have specifically tested this hypothesis in ethnically and geographically matched
      populations of RA patients and controls. We were unable to confirm previous
      observations of a TCR beta association with RA even after stratifying our study
      and control populations by HLA type.

PMID- 1352154
TI  - The diversity of the CD4+ T cell response in influenza.
AB  - We have analyzed the specificity and structural basis of the CD4+ helper T cell
      (Th) response of BALB/c mice to influenza virus. We find that many of the viral
      proteins are recognized by Th, and for one of these proteins we have defined
      eight distinct Th determinants. Moreover, Th that recognize a single determinant
      use structurally diverse T cell receptors, and display many unique specificities
      for the same determinant. These findings demonstrated extensive diversity at
      several levels of the Th response to influenza virus.

PMID- 1352155
TI  - Molecular biology of scrapie-like agents.
AB  - A detailed account is given of the nature of the causal agent of scrapie and
      other transmissible spongiform encephalopathies, with reference to proteinase
      resistant protein and its gene, subviral particles and the prion hypothesis.

PMID- 1352156
TI  - Characterization of a new hybrid mink-mouse clone panel: chromosomal and regional
      assignments of the GLO, ACY, NP, CKBB, ADH2, and ME1 loci in mink (Mustela
      vison).
AB  - To expand the mink map, we established a new panel consisting of 23 mink-mouse
      clones. On the basis of statistical criteria (Wijnen et al. 1977; Burgerhout
      1978), we developed a computer program for choice of clones of the panel.
      Assignments of the following mink genes were achieved with the use of the hybrid
      panel: glyoxalase (GLO), Chromosome (Chr) 1; acetyl acylase (ACY), Chr 5;
      creatine phosphokinase B (CKBB), Chr 10; alcohol dehydrogenase-2 (subunit B)
      (ADH2), Chr 8. Using a series of clones carrying rearrangements involving mink
      Chr 1 and 8, we assigned the gene for ME1 to the short arm of Chr 1 and that for
      ADH2 to Chr 8, in the region 8p12-p24. Mapping results confirm the ones we
      previously obtained with a mink-Chinese hamster panel. However, by means of an
      improved electrophoretic technique, we revised the localization of the gene for
      purine nucleoside phosphorylase (NP), which has been thought to be on mink Chr 2.
      It is reassigned to mink Chr 10.

PMID- 1352157
TI  - The gene for the POU domain transcription factor Oct-6 maps to the distal end of
      mouse chromosome 4.

PMID- 1352159
TI  - Framework multipoint map of the long arm of human chromosome 4 and telomeric
      localization of the gene for FSHD.
AB  - Mapping the long arm of Chromosome (Chr) 4 has assumed medical relevance with the
      establishment of linkage of facioscapulohumeral muscular dystrophy (FSHD) to
      distal 4q markers. We have constructed a multipoint linkage map using DNA markers
      that map to the long arm of Chr 4. Segregation data were collected for 17 DNA
      markers on the multigenerational CEPH mapping families, and data for one marker
      were taken from the published CEPH database. Genotypic information for six of
      these markers was also collected from a set of 24 families that exhibited
      inheritance of FSHD. Multipoint analyses allowed us to construct a map of 12
      loci, connecting two previously separate linkage groups. Significant sex-specific
      differences in recombination were found for some genetic intervals. Four loci
      from the distal region of this map showed linkage with FSHD. A map using these
      terminal markers gave the strongest support for FSHD in the most distal position
      over all other possible positions.

PMID- 1352158
TI  - The musculus-type Y chromosome of the laboratory mouse is of Asian origin.
AB  - Mus musculus domesticus, M.m. bactrianus, M.m. musculus, M.m. castaneus, and M.m.
      molossinus wild mice were investigated for polymorphisms of the Y Chromosome
      (Chr) genes Zinc finger-Y (Zfy) and Sex-determining region-Y (Sry). Zfy divided
      the Y Chrs of these mice into domesticus- (domesticus) and musculus-types
      (musculus, castaneus, molossinus). M.m. bactrianus specimens had both Y Chrs,
      possibly owing to the introgression of a musculus-type Y into this population.
      Sry identified a subpopulation of musculus-type Y chromosomes. This
      subpopulation, designated the molossinus-type, was found in M.m. molossinus, a M.
      musculus subspecies specimen from northern China (Changchun), and laboratory
      mice. The cumulative data suggest that M.m. musculus of northern China and Korea
      are a subpopulation distinct from M.m. musculus of Europe and central China and
      that this subpopulation invaded Japan, giving rise to M.m. molossinus.
      Furthermore, the data suggest that the musculus-type Y of the laboratory mouse
      originated from this subpopulation, corroborating early historical records
      reporting that Chinese and Japanese mice that were imported into Europe for the
      pet trade contributed to the genome of the laboratory mouse.

PMID- 1352161
TI  - The gene coding for variant hepatic nuclear factor 1 (Tcf-2), maps between the
      Edp-1 and Erba genes on mouse chromosome 11.

PMID- 1352160
TI  - The alpha-subunit of the skeletal muscle sodium channel is encoded proximal to Tk
      1 on mouse chromosome 11.
AB  - Recent evidence suggests that the human neuromuscular disorders, hyperkalemic
      periodic paralysis and paramyotonia congenita, are both caused by genetic defects
      in the alpha-subunit of the adult skeletal muscle sodium channel, which maps near
      the growth hormone cluster (GH) on Chromosome (Chr) 17q. In view of the extensive
      homology between this human chromosome and mouse Chr 11, we typed an interspecies
      backcross to determine whether the murine homolog (Scn4a) of this sodium channel
      gene mapped within the conserved chromosomal segment. The cytosolic thymidine
      kinase gene, Tk-1, was also positioned on the genetic map of Chr 11. Both Scn4a
      and Tk-1 showed clear linkage to mouse Chr 11 loci previously typed in this
      backcross, yielding the map order: TrJ-(Re, Hox-2, Krt-1)-Scn4a-Tk-1. No mouse
      mutant that could be considered a model of either hyperkalemic periodic paralysis
      or paramyotonia congenita has been mapped to the appropriate region of mouse Chr
      11. These data incorporate an additional locus into the already considerable
      degree of homology observed for these human and mouse chromosomes. These data are
      also consistent with the view that the conserved segment region may extend to the
      telomere on mouse Chr 11 and on human 17q.

PMID- 1352163
TI  - Lethal graft-versus-host disease in mice directed to multiple minor
      histocompatibility antigens: features of CD8+ and CD4+ T cell responses.
AB  - Lethal graft-versus-host disease (GVHD) can be induced in MHC-matched strain
      combinations which differ in their expression of multiple minor
      histocompatibility (H) antigens. It has been shown that CD8+ T cells play an
      important role in the development of disease directed to the minor H antigens,
      and that initial indications were that highly purified preparations of these
      cells were capable of mediating GVHD, without apparent 'help' from mature donor
      derived CD4+ T cells. To further strengthen this hypothesis, the current study
      was undertaken with the B10.BR----CBA strain combination in which irradiated
      recipient mice were additionally treated with an anti-CD4 monoclonal antibody, as
      a single or repeated injection, to minimize the presence of either residual host
      CD4+ cells or recently generated donor-derived CD4+ cells at later stages of
      disease development. The results indicate that these treatments do not affect the
      GVHD outcome and that the CD8+ cells are indeed capable of inducing disease
      independent of CD4+ 'help'. The addition of donor CD4+ T cells in the inoculum,
      however, does enhance the potential of these CD8+ cells, and is observed with
      both low and high dosages of CD4+ cells. CD4+ T cells, on their own, have also
      been observed to cause GVHD directed to minor H antigens in certain strain
      combinations, and their response has been further characterized in this study.
      Results indicate that CD4+ cells capable of mediating GVHD in the B10.D2----DBA/2
      strain combination can do so over a wide range of recipient irradiation
      exposures. The transfer of high dosages of CD4+ cells only shortens survival
      times of the recipients and does not afford any apparent protection phenomenon as
      previously observed in CD4+ cell mediated anti-class II MHC GVHD. The study also
      indicates that neither CD4+ nor CD8+ cells responsible for GVHD directed to minor
      H antigens seem capable of targeting host stem cell elements.

PMID- 1352162
TI  - Autologous peripheral blood stem cell transplantation after high dose therapy in
      patients with advanced lymphomas.
AB  - Thirty-eight patients with refractory or relapsed non-Hodgkin's lymphoma (19
      patients) or Hodgkin's disease (19 patients) were treated with salvage therapy.
      The peripheral stem cell collection was performed during hematologic recovery
      after myeloablative chemotherapy. In eight patients with Hodgkin's disease the
      number of CFU-GM collected was less than 0.5 x 10(4)/kg and these patients were
      excluded for stem cell transplantation. In the remaining 30 patients, a median of
      4 x 10(4) CFU-GM/kg was collected (range 0.8-100 x 10(4)/kg) by three
      leukaphereses in 25 patients and six to 11 leukaphereses in five patients.
      Conditioning regimens were CBV (eight), BEAM (six), BEAC (10) and
      cyclophosphamide + total body irradiation (TBI) (six). Without TBI, the mean time
      for reaching a granulocyte count greater than 0.5 x 10(9)/l was 18 days and for a
      platelet count greater than 50 x 10(9)/l was 19 days in 23 out of 24 patients.
      With TBI, in five patients the mean time for reaching a granulocyte count greater
      tahn 0.5 x 10(9)/l was 37 days and for a platelet count greater than 50 x 10(9)/l
      was greater than 100 days. Complications were minor. There was only one toxic
      death. The outcome in these patients was similar to that observed in patients who
      received autologous bone marrow transplantation for advanced lymphomas. In
      conclusion, we observed good hematologic recovery except when TBI was used in the
      conditioning regimen.

PMID- 1352164
TI  - A case of probable dissociative disorder.
AB  - The case of a patient with symptoms suggestive of a dissociative disorder is
      presented. The consultant reviews the diagnosis of multiple personality disorder
      (MPD) as defined in DSM-III-R and DSM-IV in relation to the patient's
      dissociative states, hallucinations, memory loss, and other symptoms. He then
      highlights the distinctions among MPD, schizophrenia, borderline personality
      disorder, major depression, and complex partial seizures. After presenting the
      conceptualization of MPD as a chronic posttraumatic stress disorder, he concludes
      with a review of treatment approaches that address the traumatic history and that
      involve hypnosis to gain access to and control dissociative states.

PMID- 1352165
TI  - The Nithsdale schizophrenia surveys. IX: Akathisia, parkinsonism, tardive
      dyskinesia and plasma neuroleptic levels.
AB  - Of all known schizophrenics living in Nithsdale, south-west Scotland, 146 (88%)
      were examined for the presence of the three principal movement disorders
      secondary to antipsychotic medication, namely akathisia, tardive dyskinesia and
      Parkinsonism. Of these, 18% had akathisia, 5% pseudoakathisia, 29% tardive
      dyskinesia, 8% persistent tardive dyskinesia, and 27% Parkinsonism. No movement
      disorder was seen in 445, 36% had one and 20% had more than one movement
      disorder. Plasma neuroleptic levels at the time of clinical assessment were
      measured by the radioreceptor technique. Correlations between dose and plasma
      level were low; the ratio of mean plasma concentration to mean dose was greatest
      with fluphenazine decanoate and lowest for sulpiride. The concentration:dose
      ratio was higher in the elderly. There was no relationship between neuroleptic
      levels and akathisia, Parkinsonism or tardive dyskinesia. Additional psychotropic
      medication influenced neuroleptic levels. In 9% of patients receiving oral
      antipsychotic medication, no drug was detected in plasma.

PMID- 1352166
TI  - Rapid tranquillisation. A survey of emergency prescribing in a general
      psychiatric hospital.
AB  - Rapid tranquillisation--giving a psychotropic to control behavioural disturbances
      -is common in medical practice, yet few surveys describe its use in psychiatric
      populations. Over five months, 102 incidents, involving 60 patients, were
      retrospectively surveyed. Patients most often involved were young white men. The
      commonest diagnosis was affective disorder (manic phase) (39%) followed by
      schizophrenia (33%). Fifteen patients were involved in 57% of the incidents. The
      majority of incidents involved injury to people or damage to property. The most
      frequently used drugs were diazepam and haloperidol, alone or in combination.
      Droperidol, chlorpromazine, sodium amytal and paraldehyde were rarely used.
      Diazepam alone or in combination with haloperidol delivered intravenously was
      most rapidly effective and was associated with greatest staff satisfaction.
      Serious side-effects were rare.

PMID- 1352167
TI  - Neural mechanisms in asthma.
AB  - Neural control of the airways may be abnormal in asthma and neurogenic mechanisms
      may contribute to the pathophysiology of asthma. Cholinergic nerves are the
      predominant bronchoconstrictor pathway in airways and cholinergic
      neurotransmission may be increased in asthma by the effects of inflammatory
      mediators on afferent nerves (reflex effect) and on prejunctional receptors on
      postganglionic nerves. In addition there may be a defect in prejunctional M2
      receptors on cholinergic nerves resulting in increased cholinergic neural
      effects. beta-Adrenoceptor function may be abnormal in asthmatic airways as a
      result of chronic inflammation, but alpha-receptors are probably unimportant in
      regulation of human airway tone. Inhibitory NANC nerves are the only
      bronchodilator pathway in human airways, and there is some evidence that the
      neurotransmitter is predominantly nitric oxide, although vasoactive intestinal
      peptide may be contributory. It is possible that i-NANC function may be abnormal
      in asthma as a consequence of inflammation. Unmyelinated sensory nerves contain a
      variety of potent inflammatory peptides, including substance P and neurokinin A,
      which might be released in chronic inflammation, particularly if there is a
      proliferation of these nerves, increased neuropeptide synthesis or reduced
      metabolism by neutral endopeptidase.

PMID- 1352168
TI  - Asthma. Bronchodilators: new developments.
AB  - This chapter is concerned with recent controversies and new developments in the
      area of established bronchodilators, namely beta-agonists, antimuscarinic drugs
      and methylxanthines. It focuses on the studies concerned with fenoterol and its
      possible role in asthma deaths in New Zealand, the new long-acting beta-agonists
      and the place of beta-agonists in the treatment of asthma. The possible reasons
      for the fact that antimuscarinic drugs have been less effective in general than
      beta-agonists in asthma are explored and the difficulties of using theophylline
      in clinical practice and its role in the treatment of asthma are discussed.

PMID- 1352169
TI  - Asthma. New therapeutic approaches.
AB  - New therapeutic approaches to asthma involve either improvements in existing
      classes of drug, or the development of novel drugs. Over the last 20 years there
      have been no new types of drug introduced, although several new classes of
      compound are now under development. Improvements in existing bronchodilators
      include long-acting inhaled beta 2-agonists, methyl xanthines with a reduced side
      effect profile and M3-selective anticholinergics. New bronchodilators include K+
      channel activators and selective phosphodiesterase inhibitors. Corticosteroids
      are the most effective anti-inflammatory drugs and there are attempts to develop
      inhaled steroids with greater topical potency or increased systemic metabolism,
      or to develop drugs which retain the anti-inflammatory effects of steroids
      without side effects. Steroids are probably effective in asthma by inhibiting the
      synthesis of cytokines and drugs which inhibit cytokine synthesis or receptors
      are now being sought. Inhibitors of mediator synthesis and receptors currently
      under development and leukotriene D4-antagonists are promising. Immunomodulatory
      drugs such as methotrexate, cyclosporin A and gold may be useful in more severe
      asthma, but drugs which modulate the immune abberation of asthma more
      specifically may be of more widespread use in the future. There is no immediate
      prospect of a cure for asthma and a drug which may be taken orally once daily and
      has no side effects would be ideal.

PMID- 1352170
TI  - Asthma. Role of T-lymphocytes and lymphokines.
AB  - It is now widely accepted that bronchial mucosal inflammation is an important
      feature of the pathogenesis of asthma. Lymphocytes probably play a role in all
      inflammatory responses which are antigen driven, since they are the only cells
      which, through the CD3/antigen receptor complex, directly recognise and respond
      to processed antigens. Activated T-lymphocytes, through the release of
      lymphokines, have the capacity to control the amount and nature of inflammatory
      responses. Increasing evidence is accumulating that activated CD4 T-lymphocytes
      participate in the inflammatory reaction observed in the asthmatic bronchial
      mucosa, by secreting lymphokines which attract and activate eosinophils and mast
      cells. CD4 T-lymphocytes may be a potentially important target for glucocorticoid
      therapy in asthma. Further characterisation of the functional properties of these
      cells might allow a definition of asthma in terms of functional abnormalities at
      the cellular level, and may uncover variability in asthma pathogenesis according
      to its aetiology.

PMID- 1352171
TI  - Involvement of cyclic guanosine monophosphate (cGMP) and cytosolic guanylate
      cyclase in the regulation of synaptic ribbon numbers in rat pineal gland.
AB  - In the rat pineal gland N-acetyltransferase (NAT) activity and synaptic ribbon
      (SR) numbers display a circadian rhythm. It is well-known that NAT activity is
      regulated by adrenergic mechanisms involving cyclic adenosine monophosphate
      (cAMP) as a second messenger. However, the mechanism involved in the regulation
      of SR numbers has not been established so far. In the present in vitro study, we
      have investigated the effects of 8-bromo-cyclic guanosine monophosphate (8-bromo
      cGMP), a cyclic guanosine monophosphate (cGMP) analog, and stimulation of
      guanylate cyclase on SR numbers. Incubation with 8-bromo-cGMP increased SR
      numbers in a dose- and time-dependent manner. Further, stimulation of the
      cytosolic guanylate cyclase also resulted in increased SR numbers. Adrenergic
      agonists stimulated cGMP but did not alter SR numbers. These findings suggest
      that cGMP is involved as a second messenger in the regulation of SR numbers.
      Since the adrenergically stimulated increase in cGMP did not influence SR
      numbers, a non-adrenergic cGMP metabolic pathway seems to be involved in the
      regulation of SR numbers in the rat pineal gland.

PMID- 1352172
TI  - Difference in distribution of glutamate-immunoreactive neurons projecting into
      the subretrofacial nucleus in the rostral ventrolateral medulla of SHR and WKY: a
      double-labeling study.
AB  - Glutamate immunoreactivity was found in 19% and 21% of the neurons of the central
      autonomic nuclei projecting into the subretrofacial nucleus (SRF) in the rostral
      ventrolateral medulla of Wistar-Kyoto rat (WKY) and spontaneously hypertensive
      rat (SHR), respectively, using a double-labeling technique in combination with
      glutamate immunocytochemistry. Double-labeled neurons were distributed in 22
      nuclei or subnuclei in the limbic system, hypothalamus, midbrain, pons and
      medulla. The average number of glutamate-immunoreactive neurons per thousand in
      SHR was significantly higher in the ipsilateral lateral parabrachial nucleus (P
      less than 0.05) and Koelliker-Fuse nucleus (P less than 0.01) than in WKY, while
      it was significantly lower in the ipsilateral medial subnucleus (P less than
      0.05) and the commissure subnucleus (P less than 0.05) of the nucleus tractus
      solitarii in SHR than in WKY. The results indicate that: (1) glutamate
      immunoreactive neurons (possibly glutamatergic) in many central autonomic nuclei
      project into the sympathetic vasomotor control neurons in the SRF; (2) the large
      population of glutamate-immunoreactive neurons in the lateral parabrachial
      nucleus and the Koelliker-Fuse nucleus of SHR is likely to increase excitatory
      inputs to the SRF vasomotor control neurons, while the smaller population of
      glutamate-immunoreactive neurons in the medial and commissure subnuclei of the
      nucleus tractus solitarii is likely to decrease excitatory inputs to the
      GABAergic neurons intrinsic to the SRF.

PMID- 1352173
TI  - Neuropeptides in the human superior cervical ganglion.
AB  - Superior cervical ganglia from 7 human cadavers (3-7 h post mortem) were
      immunostained for tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and
      14 different neuropeptides. The results show that ganglionic cells contain TH,
      DBH, neuropeptide Y (NPY), somatostatin, vasoactive intestinal polypeptide (VIP)
      and calcitonin gene-related peptide (CGRP). These substances were present
      predominantly within large ganglionic cells. Inside the ganglion, the number and
      topographical distribution of various types of immunoreactive cells differed from
      one another. NPY and CGRP immunoreactivities were found in some TH-positive
      cells, but that co-localization never exceeded the 30% of the TH cells. Leu
      enkephalin showed a weak immunoreactivity, which was restricted to fibers or
      varicosities. Neuropeptides like substance P, dynorphin A and B, cholecystokinin,
      galanin, corticotropin-releasing factor, thyrotropin-releasing hormone,
      angiotensin II and neurotensin showed no immunoreactivity in the human superior
      cervical ganglion.

PMID- 1352174
TI  - NMDA-induced increase in [Ca2+]i and 45Ca2+ uptake in acutely dissociated brain
      cells derived from adult rats.
AB  - A preparation of acutely dissociated brain cells derived from adult (3-month-old)
      rat has been developed under conditions preserving the metabolic integrity of the
      cells and the function of N-methyl-D-aspartate (NMDA) receptors. The effects of
      glutamate and NMDA on [Ca2+]i measured with fluo3 and 45Ca2+ uptake have been
      studied on preparations derived from hippocampus and cerebral cortex. Glutamate
      (100 microM) and N-methyl-DL-aspartate (200 microM) increased [Ca2+]i by 26-12 nM
      and 23-9 nM after 90 s in cerebral cortex and hippocampus, and stimulated 45Ca2+
      uptake about 16-10% in the same regions. The increases in [Ca2+]i and 45Ca2+
      uptake were inhibited by 40% in the presence of 1 mM MgCl2 and by 90-50% in the
      presence of MK-801. The results indicate (a) that a large fraction of the [Ca2+]i
      response to glutamate in freshly dissociated brain cells from the adult rat
      involves NMDA receptors, (b) when compared with results in newborn rats, there is
      a substantial blunting of the [Ca2+]i increase in adult age.

PMID- 1352175
TI  - Evidence for a postsynaptic action of the serotonergic anxiolytics: ipsapirone,
      indorenate and buspirone.
AB  - In the present experiment we analyzed whether the antianxiety action of the
      serotonergic 1A agonists buspirone (5 mg/kg), ipsapirone (5 mg/kg), indorenate (5
      mg/kg), and 8-OH-DPAT (0.5 mg/kg) were mediated through the stimulation of pre-
      or postsynaptic serotonergic receptors. The experimental anxiety values were
      determined with the burying behavior test, where a reduction in the cumulative
      time of burying behavior was interpreted as a reduction in anxiety. To that
      purpose we analyzed the putative anxiolytic action of these drugs in animals with
      lesion of the serotonergic fibers after the intracerebroventricular (ICV)
      injection of 5,7-dihydroxytyptamine (5,7-DHT, 10 or 150 micrograms/10
      microliters). The neurochemical analysis shows that these treatments produce a
      statistically significant reduction in 5-HT and 5-HIAA levels in various brain
      areas. The results of the behavioral experiments reveal that buspirone,
      ipsapirone, and indorenate produced exactly the same reduction in burying
      behavior in lesioned animals as compared with control rats. The reduction in
      burying behavior produced by 8-OH-DPAT was effectively prevented by the lesion
      with 5,7-DHT. These data suggest that the anxiolytic effect of buspirone,
      ipsapirone, and indorenate is mediated via the stimulation of postsynaptic
      receptors, while the somatodendritic receptors are involved in the antianxiety
      effect of 8-OH-DPAT.

PMID- 1352177
TI  - Bidirectional effect of beta-carboline agonists at the benzodiazepine-GABAA
      receptor chloride ionophore complex on GABA-stimulated 36Cl- uptake.
AB  - beta-Carboline agonists produced a left shift of the GABA concentration-chloride
      uptake curve or a reduction in the maximal increase in GABA-stimulated 36Cl-
      uptake depending on their concentration. The enhancement of the GABA effect
      occurs only at lower beta-carboline and GABA concentrations and is smaller for
      the partial agonist ZK 9126 compared to the full agonist ZK 93423. The opposite
      effect, inhibition of GABA-stimulated chloride conductance, is observed only at
      higher concentrations of beta-carboline agonists and GABA. The reduction of the
      GABA maximal response by the partial agonist ZK 91296 is greater than by the full
      agonist ZK 93423. The transformation of GABA-stimulated 36Cl- uptake data to
      specific chloride influx (36Cl- uptake per nM of GABA) reveals that the GABA
      concentration-response curve consists of three parts characterized by differences
      in the molar effectiveness of GABA relative to the GABA concentration. The molar
      effectiveness of GABA is a measure of the sensitivity of the GABAA receptor
      chloride ionophore complex and shows adaptive changes by this complex to
      increasing concentrations of GABA and/or beta-carboline. We conclude from our
      data that the change from GABA-sensitive to GABA-insensitive conformation of the
      GABAA receptor occurs with increasing concentrations of GABA and/or beta
      carboline. Both conformations maintain positive heterotropic cooperativity with
      beta-carboline binding sites, one responsible for positive and the other
      responsible for negative effects of beta-carboline agonists on chloride uptake.

PMID- 1352176
TI  - Somatostatin receptor elevation in rat striatum after diisopropylfluorophosphate
      administration.
AB  - The acute and chronic administration of diisopropylfluorophosphate (DFP), an
      inhibitor of acetylcholinesterase or of atropine, a blocker of muscarinic
      cholinergic receptors, did not affect somatostatin-like immunoreactivity (SLI)
      content in the striatum of rats. Acute and chronic DFP administration increased
      the number of specific 125I-Tyr11-somatostatin (125I-Tyr11-SS) receptors in cells
      dissociated from the striatum without changing the affinity constant. Although
      the increase could be blocked by pretreatment with atropine, it was not due to a
      direct effect by DFP on somatostatin (SS) receptors, because no rise in 125I
      Tyr11-SS binding was produced by high concentrations of DFP (10(-5) M) when added
      in vitro. The acute administration of atropine alone had no observable effect on
      the number of SS receptors. However, repeated atropine administration produced a
      significant decrease in the 125I-Tyr11-SS binding in cells dissociated from the
      striatum, although the affinity constant was unchanged. The results suggest that
      interactions between somatostatinergic and cholinergic receptors may be of
      importance in the rat striatum.

PMID- 1352178
TI  - Jaw muscle activity, the nucleus accumbens, and dopaminergic agonists: a new
      approach.
AB  - A method was developed to analyze electromyographic (EMG) signals in terms of
      power, viz., a measure for overall muscle activity, and number of seconds marked
      by distinct frequency ranges. With the help of this method, the effects of
      intraaccumbens administration of distilled water, the D1 receptor agonist SK&F
      38393 (SKF; 5 micrograms), the D2 receptor agonist LY 171555 (LY; 10 micrograms),
      and their combination upon the EMG signals of the masseter and the digastric
      muscle were analysed in freely moving rats. Only the combined treatment affected
      the power: The noted increase was limited to the digastric muscle. The
      time/frequency analysis was limited to frequency ranges 3-4 Hz (class A), 4-5 and
      5-6 Hz (class B), and 6-7, 7-8, ..., 12-13, and 13-14 Hz (class C). Apart from a
      small effect of SKF alone and of SKF in combination with LY on class B of the
      masseter muscle, neither SKF nor LY affected class A or B. SKF and LY increased
      and decreased, respectively, class C in both muscles. The data suggest that SKF
      and LY elicited both opposite and synergistic effects. The method is a new tool
      to analyze EMG signals in freely moving rats.

PMID- 1352179
TI  - Presynaptic dopaminergic inhibition of the spinal reflex in rats.
AB  - Dopaminergic influence on spinal monosynaptic transmission was examined in rats.
      Monosynaptic mass reflex (MMR) was recorded from the ventral root L6 following
      supramaximal stimulation (0.2 Hz; 0.1 ms) to the ipsilateral dorsal root L6 in
      spinalized rat under pentobarbitone sodium (40 mg/kg, i.p.) anaesthesia. MMR was
      inhibited by intravenous administration of the dopaminergic agonist, apomorphine
      (50-200 ug/kg) in a dose-dependent manner. The attenuatory effect of apomorphine
      (200 ug/kg i.v.) on the reflex could be reversed by the dopaminergic antagonist
      haloperidol (0.5 mg/kg, i.v.). Under tetanic stimulation (200 Hz; 15s), the
      pretetanic relative inhibition induced by apomorphine (200 ug/kg, i.v.) was
      increased only for a short period immediately after the cessation of tetanic
      stimulation. The results indicate existence of presynaptic dopamine receptors on
      the afferent terminals converging on the motoneurone which may functionally
      modulate the spinal motor output.

PMID- 1352180
TI  - [High level of tumor necrosis factor alpha activity of plasma and serum from
      acute phase hemorrhagic fever with renal syndrome].
AB  - The level of TNF-alpha activity of plasma and serum from HFRS acute phase
      patients was investigated. The level of TNF (tumor necrosis factor) activity of
      plasma and serum from acute phase patients was higher than that of plasma and
      serum from convalescent phase patients or from normal group. The higher TNF
      activity of plasma or serum from acute phase patients was due to TNF-alpha,
      because the TNF activity was almost completely inhibited by polyclonal mouse
      serum against rHuTNF-alpha. Also, the increase in TNF-alpha positive ratio of
      PBMC from acute phase HFRS patients was found as compared to convalescent phase
      patients or to normal group. All these results strongly suggest that high level
      of TNF-alpha activity of plasma and serum may be involved in the development of
      clinic symptoms and pathological lesions during the course of HFRS disease.

PMID- 1352181
TI  - Atherosclerosis in internal mammary arteries selected for coronary artery bypass
      grafting.
AB  - Atheromas are infrequent in the internal mammary artery (IMA) which is now the
      conduit of choice for coronary artery bypass grafting (CABG). Described are two
      cases of significant atherosclerotic stenosis near the distal ends of IMAs
      selected for CABG.

PMID- 1352182
TI  - [Proceedings of the 1992 congress and scientific meeting of the Chinese Medical
      Association. Abstracts].

PMID- 1352183
TI  - Immunohistochemical identification of P-glycoprotein in previously untreated,
      diffuse large cell and immunoblastic lymphomas.
AB  - Expression of P-glycoprotein has been linked to multidrug resistance in cancer
      cell lines and human tumors. We investigated the frequency and clinical
      significance of P-glycoprotein immunoreactivity in 57 previously untreated
      diffuse large cell and immunoblastic lymphomas. Banked frozen tissue, which had
      been obtained prior to chemotherapy, was tested for reactivity with 2 monoclonal
      antibodies (MRK16 and C219) that recognize different domains of P-glycoprotein,
      using an immunoperoxidase technique. Thirteen of 57 lymphomas (23%) showed strong
      staining of greater than 50% of neoplastic cells; 15 of 57 (26%) showed labeling
      of a minority (11-50%) of neoplastic lymphocytes; 14 of 57 (25%) yielded
      equivocal results (reactivity in less than 10% of cells); and 15 of 57 (26%) were
      negative for P-glycoprotein. The 2 monoclonal antibodies were comparable in
      reactivity. Expression of MDR-1 mRNA was determined in 6 cases with sufficient
      available tissue, and did not correlate well with the percentages of cells
      reactive for P-glycoprotein by immunohistochemistry. Thirty-nine of our 57
      patients completed multiagent chemotherapy. Contrary to our expectations, we
      found that P-glycoprotein immunoreactivity did not decrease the likelihood of
      response to induction chemotherapy. Median survival also was not adversely
      affected.

PMID- 1352184
TI  - Taxol blocks processes essential for prostate tumor cell (PC-3 ML) invasion and
      metastases.
AB  - We have examined the antimetastatic effects of taxol on a PC-3 human prostatic
      tumor variant (PC-3 ML) which metastasizes to the lumbar vertebrae in severe
      combined immunodeficiency-carrying (SCID) mice. Immunofluorescence labeling
      indicated that taxol (0.5 to 1.0 microM for 6 h) produced an abnormal bundling of
      microtubules in a dosage-dependent manner. Slot blotting and gelatinase assays
      revealed that taxol inhibited secretion of the M(r) 72,000 and M(r) 92,000 type
      IV collagenases plus a M(r) 57,000 gelatinase. Radioimmunoprecipitation
      measurements confirmed that the drug inhibited both the secretion and the
      synthesis of the M(r) 72,000 collagenase. Taxol also blocked total protein
      secretion but did not influence total protein synthesis or turnover. Boyden
      chamber chemotactic studies further showed that taxol (0.5 to 1.0 microM)
      inhibited invasion of Matrigel. More importantly, studies in SCID mice
      demonstrated that taxol (50 to 250 mg/m2/day) blocked the establishment, growth,
      and long-term survival of PC-3 ML cells.

PMID- 1352185
TI  - Ultrastructural identification and distribution of the adhesion molecules ICAM-1
      and LFA-1 in the vascular and extravascular compartments of the human palatine
      tonsil.
AB  - Immunohistological analysis of sections prepared from human palatine tonsils
      revealed marked differences in the distribution of the adhesion molecule,
      leucocyte function antigen-1 (LFA-1) and its counter receptor, intercellular
      adhesion molecule-1 (ICAM-1). Light microscopy showed that LFA-1 was restricted
      to the leucocytes, particularly the lymphocytes. In contrast, staining of ICAM-1
      was predominantly confined to the vascular endothelium with the greatest
      expression seen on the morphologically distinct high endothelial venules in the
      parafollicular areas; these are the sites that appear to support lymphocyte
      migration. Electron microscopy revealed that ICAM-1 was present on the luminal
      and lateral surfaces of the high endothelium and absent from the abluminal
      surface supported by basal lamina. The ICAM-1 was also absent from those surfaces
      of the endothelium that were in close contact with intravascular lymphocytes.
      Other cells stained by the anti-ICM-1 antibody included dendritic cells, plasma
      cells and epithelial cells in the reticulated crypt epithelium and in the upper
      strata of the non-keratinised stratified squamous epithelium. The high expression
      of LFA-1 was most prominent on lymphocytes, low on antigen-presenting cells and
      activated lymphoid cells, and not detectable on plasma cells, epithelial and
      endothelial cells. We propose that LFA-1/ICAM-1 binding participates in mediating
      the transendothelial migration of lymphocytes across the high endothelial venules
      of palatine tonsil.

PMID- 1352186
TI  - Distribution of catecholaminergic and serotoninergic systems in forebrain and
      midbrain of the newt, Triturus alpestris (Urodela).
AB  - Mapping of monoaminergic systems in the brain of the newt Triturus alpestris was
      achieved with antisera against (1) thyrosine hydroxylase (TH), (2) formaldehyde
      conjugated dopamine (DA), and (3) formaldehyde-conjugated serotonin (5-HT). In
      the telencephalon, the striatum was densely innervated by a large number of 5-HT
      , DA- and TH-immunoreactive (IR) fibers; IR fibers were more scattered in the
      amygdala, the medial and lateral forebrain bundles, and the anterior commissure.
      In the anterior and medial diencephalon, TH-IR perikarya contacting the
      cerebrospinal fluid (CSF-C perikarya) were located in the preoptic recess organ
      (PRO), the organum vasculosum laminae terminalis and the suprachiasmatic nucleus.
      Numerous TH-IR perikarya, not contacting the CSF, were present in the posterior
      preoptic nucleus and the ventral thalamus. At this level, DA-IR CSF-C neurons
      were only located in the PRO. In the posterior diencephalon, large populations of
      5-HT-IR and DA-IR CSF-C perikarya were found in the paraventricular organ (PVO)
      and the nucleus infundibularis dorsalis (NID); the dorsal part of the NID
      additionally presented TH-IR CSF-C perikarya. Most regions of the diencephalon
      showed an intense monoaminergic innervation. In addition, numerous TH-IR, DA-IR
      and 5-HT-IR fibers, originating from the anterior and posterior hypothalamic
      nuclei, extended ventrally and reached the median eminence and the pars
      intermedia of the pituitary gland. In the midbrain, TH-IR perikarya were located
      dorsally in the pretectal area. Ventrally, a large group of TH-IR cell bodies and
      some weakly stained DA-IR and 5-HT-IR neurons were observed in the posterior
      tuberculum. No dopaminergic system equivalent to the substantia nigra was
      revealed. The possible significance of the differences in the distribution of TH
      IR and DA-IR neurons is discussed, with special reference to the CSF-C neurons.

PMID- 1352187
TI  - Gastrulation in the mouse: the role of the homeobox gene goosecoid.
AB  - Mouse goosecoid is a homeobox gene expressed briefly during early gastrulation.
      Its mRNA accumulates as a patch on the side of the epiblast at the site where the
      primitive streak is first formed. goosecoid-expressing cells are then found at
      the anterior end of the developing primitive streak, and finally in the
      anteriormost mesoderm at the tip of the early mouse gastrula, a region that gives
      rise to the head process. Treatment of early mouse embryos with activin results
      in goosecoid mRNA accumulation in the entire epiblast, suggesting that a
      localized signal induces goosecoid expression during development. Transplantation
      experiments indicate that the tip of the murine early gastrula is the equivalent
      of the organizer of the amphibian gastrula.

PMID- 1352190
TI  - The use of psychotropic medications in clinical dermatology.
AB  - In this article, the use of selected psychopharmacologic medications was
      explained in detail. If a patient who is obviously suffering from a psychiatric
      component of his or her disorder that can be responsive to psychopharmacotherapy
      refuses to accept a referral to a psychiatrist or other mental health
      professional, the dermatologist must decide whether to use these medications. If
      he or she decides to use these medications, it should always be remembered that
      the choice of psychopharmacologic treatment depends on the nature of the
      underlying psychopathology-anxiety, psychosis, depression, or compulsion-rather
      than on the dermatologic label such as neurotic excoriations. It is the hope of
      the author that more patients who fall into this interface between psychiatry and
      dermatology will be helped if dermatologists become more familiar with the
      availability and use of these medications.

PMID- 1352189
TI  - Gonadotrophin secretion in vitro by cells of a pituitary tumour from a patient
      with multiple endocrine neoplasia type I.
AB  - OBJECTIVE: The aim was to investigate the hormone secretory products of a
      pituitary tumour from a patient with multiple endocrine neoplasia type I (MEN I)
      utilizing cell culture and immunoassay techniques. DESIGN: Adenoma tissue was
      enzymically dispersed and established in cell culture. Medium was collected for
      hormone measurement after 2 days, and also after 24-hour periods during long-term
      culture. In addition, tissue fixed at surgery was analysed by immunocytochemistry
      and electron microscopy. PATIENT: The subject was a 59-year-old male with a
      clinical history characteristic of familial MEN I syndrome. MEASUREMENTS:
      Pituitary hormones in serum and culture medium were measured by fully
      characterized radioimmunoassays. RESULTS: Preoperative serum LH and FSH levels
      were normal, or slightly elevated, and there was a progressively blunted
      gonadotrophin response to GnRH throughout the 8 years prior to adenomectomy. TRH
      induced a small, paradoxical increase in serum gonadotrophin levels 2 weeks
      preoperatively. Post-operative pituitary hormone responses to standard
      stimulation tests showed an active normal pituitary. In vitro, the pituitary
      tumour cells secreted only gonadotrophins and glycoprotein hormone alpha-subunit.
      The fixed tumour tissue immunostained for alpha-subunit alone, and electron
      microscopy confirmed the presence of secretory granules with diameters of 100-280
      nm. Gonadotrophin secretion continued throughout 77 days in long-term culture,
      but whilst LH was released at a steady rate, that of FSH transiently increased
      between days 29 and 48 in vitro. CONCLUSIONS: These data demonstrate that a
      pituitary tumour associated with the MEN I syndrome secreted gonadotrophins in
      vitro.

PMID- 1352188
TI  - Structure and expression of a plastid-encoded groEL homologous heat-shock gene in
      a thermophilic unicellular red alga.
AB  - A gene homologous to the E. coli groEL locus was identified on the plastid genome
      of the unicellular red alga Cyanidium caldarium strain 14-1-1 (synonym: Galdieria
      sulphuraria). The complete nucleotide sequence was determined and compared to
      bacterial- and nuclear-encoded counterparts of higher plants. At the amino-acid
      level the C. caldarium gene shows 70% homology to the corresponding gene of the
      cyanobacterium Synechococcus and 52% homology to nuclear-encoded counterparts of
      higher plants, respectively. Northern and Western blot experiments were used to
      investigate the dependence of the transcript- and protein-level on culture
      temperature and heat shock.

PMID- 1352191
TI  - Predischarge exercise echocardiography in patients with unstable angina who
      respond to medical treatment.
AB  - The diagnostic and prognostic value of predischarge exercise echocardiography
      (echo) was assessed prospectively in 36 patients with unstable angina soon after
      stabilization on medical treatment. Two-dimensional echo was performed at rest
      and immediately after a symptom-limited exercise test. Patients with previous
      myocardial infarction, coronary revascularization, left bundle-branch block and
      dilated cardiomyopathy were excluded. Left ventricular regional wall motion was
      analyzed visually and a wall motion score index (WMSI) was derived. Patients were
      followed prospectively for an average period of 26 months (range 16-34 months).
      The study end points were a new cardiac event defined as acute myocardial
      infarction or a need for coronary revascularization because of a recurrence of
      severe medically refractory angina. Sixteen patients (44%) had positive exercise
      electrocardiography (ECG), while exercise echo was positive in 22 patients (61%).
      Of 28 patients undergoing coronary angiography, 23 had significant coronary
      artery disease (CAD). The sensitivity of exercise ECG in detecting CAD was 61%
      while the corresponding result was 83% for exercise echo. Cardiac events occurred
      in 21 patients (58%). Exercise ECG was positive in 12 of these patients (57%),
      while a positive exercise echo was found in 17 patients (81%). There were
      significantly more patients with positive exercise echo among patients
      experiencing cardiac events than among those without cardiac events (p less than
      0.01). In patients with CAD, WMSI decreased significantly after exercise (p less
      than 0.05). Exercise WMSI was also significantly lower in patients with CAD than
      in those without CAD (p less than 0.02). Exercise WMSI also discriminated
      patients with cardiac events from those without such events (p less than
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352192
TI  - Leukocyte adhesion deficiency presenting with recurrent otitis media and
      persistent leukocytosis.

PMID- 1352194
TI  - IVth International Symposium for Health Professionals in Rheumatology. Harrogate,
      10-12 June 1992. Abstracts.

PMID- 1352193
TI  - What's new in tocolytics.
AB  - Tocolytic therapy represents the final obstetric end point in the prevention of
      premature births. For the past two decades, betamimetic therapy has been the
      mainstay of tocolytic therapy. Newer agents, indomethacin and nifedipine, offer
      new hope in the treatment of premature labor. With the introduction of these
      newer agents, combination drug therapy appears to be on the horizon.

PMID- 1352195
TI  - A once-daily oral antibiotic: the way ahead in community-acquired infection. A
      Roxithromycin Symposium presented at the 17th International Congress of
      Chemotherapy. Berlin, Germany, 23-27 June 1991.

PMID- 1352196
TI  - Use of alpha-methyl-tyrosine for refractory hypertension in a child with
      neuroblastoma.

PMID- 1352197
TI  - Nosocomial pneumonia in the critically ill: product of aspiration or
      translocation.

PMID- 1352198
TI  - Somatostatin in gastric juice in normal subjects and patients with duodenal
      ulcer.
AB  - Somatostatin in gastric juice was determined in normal subjects and patients with
      duodenal ulcer. Gel exclusion chromatography of gastric juice revealed that the
      main immunoreactivity existed at the position of somatostatin-14. A large amount
      of somatostatin was present in gastric juice, and the quantity increased
      following tetragastrin stimulation. Furthermore, there was a good inverse
      correlation between somatostatin concentration and acidity of gastric juice;
      however, there was no difference between normal subjects and patients with
      duodenal ulcer in the amount of somatostatin released into gastric juice.

PMID- 1352199
TI  - Effects of oleic acid and endogenous bile on duodenal secretion of somatostatin
      in man.
AB  - We studied the effects of intraduodenal oleic acid on the release of somatostatin
      to plasma and the correlation between endogenous bile output and plasma
      somatostatin. In five normal persons infusion of 0, 5, 10, 20, and 40 mM oleic
      acid dose-dependently increased the levels of somatostatin during as well as
      after gallbladder emptying. The difference between somatostatin concentration
      during and after gallbladder emptying was not significant. The amylase secretion
      also was significantly correlated to the dose of fat, whereas the output of bile
      salts was the same for all fat doses used. Our observations indicate that
      intraduodenal oleic acid--and not bile salts--releases somatostatin from the gut.

PMID- 1352200
TI  - Effect of portacaval anastomosis on glutamine synthetase activities in liver,
      brain, and skeletal muscle.
AB  - Glutamine synthetase is responsible for the ATP-dependent amidation of glutamate
      to glutamine. In liver the enzyme is highly localized in perivenous hepatocytes;
      in brain the enzyme is localized in astrocytes. Portacaval anastomosis resulted
      in liver atrophy, hyperammonemia, and up to 90% loss of glutamine synthetase
      activity in liver homogenates. This effect, which appears to be irreversible,
      probably reflects the selective loss of perivenous hepatocytes following
      portacaval anastomosis. Glutamine synthetase activities in brain were unaffected
      by portacaval anastomosis of up to 12 weeks' duration. Enzyme activities in
      homogenates of skeletal muscle, on the other hand, were significantly increased
      at one and four weeks after shunt surgery. These effects were not the result of
      decreased food intake in shunted animals. These findings suggest fundamentally
      different regulatory mechanisms for glutamine synthetase in these tissues.
      Skeletal muscle may thus provide an important alternative site for ammonia
      detoxification after portal-systemic shunting.

PMID- 1352201
TI  - Influence of P-4502E1 induction on benzene metabolism in rat hepatocytes and on
      biliary metabolite excretion.
AB  - The influence of P-4502E1 induction on the metabolite pattern of benzene was
      studied in hepatocytes in vitro and in bile in vivo, and compared with that
      obtained with phenol (the major benzene metabolite). Eight metabolites from
      benzene and four from phenol (including conjugates) represented over 90% of total
      metabolites. Benzene metabolism (0.1 mM) in hepatocytes from isopropanol-treated
      rats (2.5 ml/kg, orally) was 3-fold higher than in corresponding cells from
      control rats, primarily because of increased formation of hydroquinone and
      phenylglutathione. Immunoblotting of microsomes revealed a parallel induction of
      P-4502E1 in hepatocytes from isopropanol-treated rats. In contrast, treatment
      with 3-methylcholanthrene or phenobarbital caused a decrease of P-4502E1,
      together with reduced benzene metabolism at 0.01 mM benzene. Addition of
      isoniazid (5 mM) resulted in a strong inhibition of benzene and phenol
      metabolism. Benzene metabolites were determined in bile following intraperitoneal
      administration of benzene (2.5 and 150 mg/kg). Biliary benzene metabolites were
      increased 2- to 3-fold after isopropanol treatment. Hydroquinone sulfate was
      identified as a major biliary metabolite of phenol. The results suggest that
      treatment with inducers of P-4502E1 leads, even at low benzene exposure, to an
      increased release of potentially myelotoxic metabolites from liver into the
      systemic circulation.

PMID- 1352202
TI  - Identification of the antibiotic hops component, colupulone, as an inducer of
      hepatic cytochrome P-4503A in the mouse.
AB  - A higher level of cytochrome P-450 (P450)-dependent ethylmorphine (EM) N
      demethylase activity was observed in hepatic microsomes from mice fed a natural
      ingredient diet ("crude diet") than in those from mice fed a semi-purified diet
      ("purified diet"). This led to the testing of individual ingredients of the crude
      diet as inducers of the P-450 system. Brewers yeast proved to be the most
      significant inductive component of the crude diet. Further investigation revealed
      that hop components (lupulones) absorbed on yeast during the brewing process were
      responsible for the induction of the P-450 system. The induction of P-450 and
      several P-450-dependent monooxygenase activities (EM N-demethylation, aniline
      hydroxylation, benzo[a]pyrene hydroxylation) by colupulone with respect to dose
      and time course were investigated. The very large increase in EM N-demethylase
      activity elicited by colupulone suggested that P-4503A had been induced. Western
      blot technology verified this speculation. Western blot analysis of microsomal
      protein from mice fed hops, brewers yeast, or the residue of a hexane extract of
      hops supported the conclusion that all of these substances induced P-4503A. These
      substances were also relatively good inducers of P-4502B, but not as inductive of
      this isozyme as the crude diet. This is interpreted to mean that not all of the
      inductive properties of the crude diet are due to hop components. These studies
      question the use of crude commercial diets in studies of P-450 systems. They may
      also challenge some current definitions of "constitutive" and "induced" P-450s.

PMID- 1352203
TI  - Disposition and pharmacokinetics of [14C]finasteride after oral administration in
      humans.
AB  - The disposition of [14C]finasteride, a competitive inhibitor of steroid 5 alpha
      reductase, was investigated after oral administration of 38.1 mg (18.4 microCi)
      of drug in six healthy volunteers. Plasma, urine, and feces were collected for 7
      days and assayed for total radioactivity. Concentrations of finasteride and its
      neutral metabolite, omega-hydroxyfinasteride (monohydroxylated on the t-butyl
      side chain), in plasma and urine were determined by HPLC assay. Mean excretion of
      radioactivity equivalents in urine and feces equaled 39.1 +/- 4.7% and 56.8 +/-
      5.0% of the dose, respectively. The mean peak plasma concentrations reached for
      total radioactivity (ng equivalents), finasteride, and omega-hydroxyfinasteride
      were 596.5 +/- 88.3, 313.8 +/- 99.4, and 73.7 +/- 11.8 ng/ml, respectively, at
      approximately 2 hr; the mean terminal half-life for drug and metabolite was 5.9
      +/- 1.3 and 8.4 +/- 1.7 hr, respectively. Of the 24-hr plasma radioactivity,
      40.9% was finasteride, 11.8% was the neutral metabolite, and 26.7% was
      characterized as an acidic fraction of radioactivity. Binding of [14C]finasteride
      to plasma protein was extensive (91.3 to 89.8%), with a trend suggesting
      concentration dependency (range 0.02 to 2 micrograms/ml). Little of the dose was
      excreted in urine as parent (0.04%) or omega-hydroxyfinasteride (0.4%). Urinary
      excretion of radioactivity was largely in the form of acidic metabolite(s)--18.4
      +/- 1.7% of the dose was eliminated as the omega-monocarboxylic acid metabolite.
      Finasteride was scarcely excreted unchanged in feces. In humans, finasteride is
      extensively metabolized through oxidative pathways.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1352204
TI  - Methacrylonitrile: in vivo metabolism to cyanide in rats, mice, and gerbils.
AB  - Methacrylonitrile (MeAN), a widely used industrial chemical, is metabolized to
      cyanide in rats, mice, and gerbils. Cyanide levels following oral administration
      of 0.5 or 1 LD50 dose of MeAN were determined in blood and organs of treated
      animals. Male Mongolian gerbils were 50-fold more sensitive to MeAN than Sprague
      Dawley rats and about 5-fold more sensitive than were Albino-Swiss mice. The
      signs of MeAN toxicity were typically those of cyanide-related central nervous
      system poisoning in all the three species. The difference was in the time
      required for the onset of these signs. Mice and gerbils developed the toxicity
      signs faster than the rats. All the three species showed a dose-response
      relationship in metabolism of MeAN to cyanide. However, in mice and gerbils, the
      peak blood concentration of cyanide occurred 1 hr following MeAN administration,
      whereas it took 3 hr for rats to reach peak blood cyanide levels. In the rats
      treated with phenobarbital or those starved for 18 hr, the metabolism of MeAN to
      cyanide increased significantly (159-178% and 181-201% of control, respectively),
      and the treatment of rats with CoCl2 resulted in a significant decrease in MeAN
      metabolism to cyanide (60-68% of control). These studies indicate a distinct
      species difference in the toxicity and metabolism of MeAN.

PMID- 1352205
TI  - Identification of biliary metabolites of m-dichlorobenzene in rats.
AB  - At least 12 metabolites were observed in the bile of rats administered with m
      dichlorobenzene in the preliminary experiments by HPLC. Some of them were assumed
      to be conjugates containing phenyl and dihydro-hydroxyphenyl moieties with
      glutathione or cysteine by enzymatic and thermal reactions. To isolate these
      metabolites, the bile collected from 20 rats administered with 500 mg/kg of m
      dichlorobenzene and 300 mg/kg of cysteine was separated into five fractions by
      HPLC. Eighteen metabolites were isolated from these fractions by TLC and HPLC.
      The chemical structure of the major metabolite excreted was determined as trans
      2,4-dichloro-6-(glutathion-S-yl)cyclohexa-2,4-dien+ ++-1-ol by 13C-NMR, 1H-NMR,
      FAB-MS, and some reaction experiments. The metabolite excreted in the secondary
      largest amount was identified as its positional isomer, trans-3,5-dichloro-6
      (glutathion-S-yl)cyclohexa-2,4-dien+ ++-1-ol. Their diastereomers were also
      observed in the bile. trans-2,4-Dichloro-6-(cystein-S-yl)cyclohexa-2,4-dien- 1-ol
      and its positional isomer, which were possibly derived from glutathione
      conjugates above, were also identified. 3,5-Dichlorophenyl conjugates with
      glutathione or cysteine and 3,5-dichlorophenyl mercapturic acid, and their 2,4
      dichlorophenyl isomers, were excreted. Three monochlorophenol conjugates, of
      which chemical structures were still not established, were present in the bile.

PMID- 1352206
TI  - Glucuronidation of the dopamine D-1 receptor antagonists NNC 0756 and NNC 0772 in
      liver microsomes.
AB  - Glucuronidation of the two enantiomeric dopamine D-1 antagonists, NNC 0756 ([(+)
      8-chloro-7-hydroxy-5-(2,3-dihydrobenzofuran-7-yl)-3-methyl- 2,3,4,5,tetrahydro-1H
      3-benzazepine, acetate]) and NNC 0772 [(-)-8-chloro-7-hydroxy-5-(2,3
      dihydrobenzofuran-7-yl)-3-methyl-2,3,4,5- tetrahydro-1H-3-benzazepine, HCl], was
      studied in rat and human liver microsomes. In rats, the reaction exhibited
      biphasic kinetics for both enantiomers as shown by Eadie-Hofstee plots. Both the
      high- and low-affinity reactions showed a high degree of stereoselectivity,
      primarily because of the large differences in Km values. For the high- and low
      affinity reactions, the (-)-enantiomer, NNC 0772, had a 4- and 6-fold higher Km
      value, respectively. The difference in Vmax values were less significant, with
      3.0- and 1.1-fold higher values for the (-)-enantiomer. Treatment of rats with
      known inducers of UDP-glucuronosyltransferases, phenobarbital, and 3-methyl
      cholanthrene, did not change the kinetics of the reaction. Glucuronidation of the
      (+)-enantiomer, NNC 0756, was competitively inhibited in rat liver microsomes by
      the closely related structure, SCH 23388 [S-(-)-8-chloro-7-hydroxy-5-phenyl-3
      methyl-2,3,4,5-tetrahydro-1H-3- benzazepine], with an apparent Ki value of 90
      microM. Morphine and 4-hydroxybiphenyl, both known substrates of
      glucuronosyltransferase, did also inhibit the reaction with Ki values of 604 and
      55 microM, respectively. In contrast to rats, glucuronidation of NNC 0756 in
      human liver microsomes followed Michaelis-Menten kinetics, suggesting the
      involvement of a single form of glucuronosyltransferase or possibly two forms,
      with similar affinity for NNC 0756.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352207
TI  - Stereoselective renal tubular secretion of a new uricosuric diuretic, 6,7
      dichloro-5-(N,N-dimethylsulfamoyl)-2,3-dihydro-2-benzofurancarboxyl ic acid (S
      8666), in cynomolgus monkeys.
AB  - Plasma concentration-time curves and urinary excretion of individual enantiomers
      of unchanged S-8666 and its N-monodemethylated metabolite, M-1, in male
      cynomolgus monkeys were measured after oral administration of racemic S-8666 at
      doses of 5, 10, and 50 mg/kg and also after intravenous injection at doses of 1,
      5, and 10 mg/kg. The Tmax values for individual enantiomers of S-8666 in fasted
      male monkeys were 30 min after oral administration. The AUC values for S(-)-S
      8666 were greater than those for R(+)-S-8666 and oral dose-AUC relationships of
      both enantiomers showed a linearity over the dose range used. Most of the S-8666
      and a trace of M-1 were excreted in the first 24-hr urine, with no evidence of
      stereoselectivity from the amounts excreted. Since large portions were recovered
      from the urine as unchanged S-8666 after intravenous injection, most excretion
      occurs via the kidney. The t1/2 beta values and the Vdss for S(-)-S-8666 after
      intravenous injection were smaller than those for R(+)-S-8666. The CLt and the
      CLr values decreased with increasing intravenous doses, indicating saturation at
      a renal excretion process at high plasma concentrations of S-8666. The CLt and
      CLr values for R(+)-S-8666 were greater than those for the S(-)-enantiomer. The
      unbound fraction of R(+)-S-8666 in plasma was significantly greater than that of
      S(-)-S-8666 [21.6% for R(+), 12.0% for S(-)]. Renal clearance for the unbound
      fraction of S(-)-S-8666 was greater than that of R(+)-S-8666, suggesting
      stereoselective renal tubular secretion.

PMID- 1352208
TI  - Isolation of two immunosuppressive metabolites after in vitro metabolism of
      rapamycin.
AB  - Rapamycin was incubated with human liver microsomes and an NADPH regenerating
      system, the metabolites were purified by semipreparative HPLC, and their
      structures were elucidated by direct chemical ionization and FAB-MS. At least six
      fractions were isolated containing rapamycin metabolites, indicating that
      rapamycin is metabolized by the human liver cytochrome P-450 system. One of these
      metabolites was identified as 41-O-demethyl-rapamycin. A second metabolite was
      hydroxylated in a yet unknown position. These two metabolites retained
      immunosuppressive activity in a phytohemagglutinin-stimulated human lymphocyte
      assay with IC50S of 1 and 1.5 nmol/liter, respectively. Rapamycin was metabolized
      by rat small intestinal microsomes to at least two metabolites, indicating extra
      hepatic metabolism of rapamycin.

PMID- 1352209
TI  - Evidence for urinary excretion of glucuronide conjugates of nicotine, cotinine,
      and trans-3'-hydroxycotinine in smokers.
AB  - Urinary nicotine metabolic output was profiled for 11 smokers who smoked their
      regular cigarette brands ad libitum. Thermospray liquid chromatography/mass
      spectrometry was used to monitor nicotine and eight metabolites, including
      glucuronide conjugates of nicotine, cotinine, and trans-3'-hydroxycotinine that
      were determined indirectly using enzyme hydrolysis. These results were used to
      estimate an average, steady-state concentration in a 24-hr urine sample during ad
      libitum smoking and to assess interindividual variability in the excretion of
      these metabolites. The variability in absolute amount among the nine analytes
      ranged from 35 to 70% for these smokers. The glucuronide conjugates constituted
      an average of 29% of all urinary metabolites monitored in this study. trans-3'
      Hydroxycotinine in the free form constitutes the largest single metabolite in
      smokers' urine, with an average of 35% of the total. The sums of nicotine
      metabolites determined here are very close to the Federal Trade Commission yields
      of nicotine for the total number of cigarettes smoked by these subjects during
      the urine collection interval. These results indicate that a large proportion of
      the nicotine absorbed while smoking can be accounted for as urinary metabolites
      of nicotine, including glucuronide conjugates of nicotine, cotinine, and trans-3'
      hydroxycotinine.

PMID- 1352210
TI  - Comparative metabolism and disposition of furfural and furfuryl alcohol in rats.
AB  - The comparative metabolism and disposition of furfural (FAL) and furfuryl alcohol
      (FOL) were investigated following oral administration of approximately 0.001,
      0.01, and 0.1 of the LD50, corresponding to approximately 0.127, 1.15, and 12.5
      mg/kg for FAL and 0.275, 2.75, and 27.5 mg/kg for FOL. At all doses studied, at
      least 86-89% of the dose of FAL or FOL was absorbed from the gastrointestinal
      tract. FAL and FOL were extensively metabolized prior to excretion. The major
      route of excretion was in urine, where 83-88% of the dose was excreted, whereas 2
      4% was excreted in the feces. Approximately 7% of the dose from rats treated with
      FAL at 12.5 mg/kg was exhaled as 14CO2. At 72 hr following administration, the
      pattern of tissue distribution of radioactivity was similar for both FAL and FOL.
      Liver and kidney contained the highest, and brain the lowest concentrations of
      radioactivity. Generally, the concentrations of radioactivity in tissues were
      proportional to the dose. Almost all of the urinary radioactivity was tentatively
      identified. No FAL or FOL was detected in urine. Furoylglycine was the major
      urinary metabolite (73-80% of dose), and furoic acid (1-6%) and furanacrylic acid
      (3-8%) were the minor metabolites following treatment with either FAL or FOL.
      Therefore, the initial step in the metabolism of FAL and FOL involves the
      oxidation to furoic acid, which is excreted unchanged and decarboxylated to form
      14CO2, conjugated with glycine, or condensed with acetic acid.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1352211
TI  - Metabolism of isoniazid by activated leukocytes. Possible role in drug-induced
      lupus.
AB  - The tuberculostatic agent isoniazid has been implicated in inducing various
      idiosyncratic reactions including drug-induced lupus. The mechanism is unknown
      but may involve a reactive metabolite of the drug. Isoniazid was oxidized by
      activated leukocytes to isonicotinic acid. Myeloperoxidase is likely the enzyme
      in the leukocyte involved, since the oxidation was inhibited by azide, which
      inhibits myeloperoxidase, and by catalase, which catalyzes the breakdown of
      hydrogen peroxide. The same metabolic profile was observed when isoniazid was
      incubated with purified myeloperoxidase and hydrogen peroxide. The rate of the
      reaction was increased in the presence of chloride. Hypochlorous acid was also
      able to oxidize isoniazid to isonicotinic acid. Isoniazid, or an oxidative
      product, inhibited the reaction when high initial substrate concentrations were
      used. Isoniazid is oxidized by activated leukocytes, possibly to a reactive
      intermediate, which may have implications for isoniazid-induced lupus.

PMID- 1352212
TI  - Systemic pharmacokinetics of acitretin, etretinate, isotretinoin, and acetylenic
      retinoids in guinea pigs and obese rats.
AB  - Etretinate, a highly lipophilic retinoid, is known to accumulate in the human
      body with a slow systemic elimination (half-life approximately 100 days) after
      long-term treatment. Retinoids with high lipophilicity and slow body elimination
      have the propensity of eliciting teratogenic effects. Therefore, synthetic
      retinoids with reduced systemic retention are desired. In this study, we
      evaluated the systemic pharmacokinetics of acitretin, etretinate, isotretinoin,
      synthetic acetylenic retinoic acids (AGN 190121, AGN 190186, and AGN 190299), and
      acetylenic retinoates (AGN 190073, AGN 190089, and AGN 190168) in guinea pigs
      following iv doses. Their pharmacokinetics were also measured in obese rats to
      probe the effect of body fat on the drug disposition of retinoids. The acetylenic
      retinoates were hydrolyzed to their corresponding free acids at a much faster
      rate than etretinate in both animal species. All retinoates showed faster body
      clearance and larger volume of distribution than their free acids. In the obese
      rats, longer elimination half-lives and slower body clearance of the retinoids,
      except isotretinoin, were observed as compared to those in the normal rats. These
      results suggest that body fat has a significant effect on drug disposition and
      slows down the systemic clearance of retinoids. Since the synthetic acetylenic
      retinoates rapidly converted to their less lipophilic free acids after systemic
      absorption, the potential accumulation of these retinoids, as reported for
      lipophilic etretinate, were unlikely to occur in humans and animals.

PMID- 1352213
TI  - Correlations between conceptal concentrations of all-trans-retinoic acid and
      dysmorphogenesis after microinjections of all-trans-retinoic acid, 13-cis
      retinoic acid, all-trans-retinoyl-beta-glucuronide, or retinol in cultured whole
      rat embryos.
AB  - Retinol (4,000 ng/ml), all-trans-retinoyl-beta-glucuronide (4,000 ng/ml), and 13
      cis-retinoic acid (1,500 ng/ml) each produced dysmorphogenic effects
      qualitatively similar to those elicited by 250 ng/ml of all-trans-retinoic acid
      after microinjections of the respective individual retinoids into the amniotic
      cavities of cultured whole rat embryos. Subsequent HPLC analyses of the cultured
      whole conceptuses, embryos proper, yolk sacs, and culture media (24 hr after
      microinjections) indicated that conceptal biotransformation of each of the
      retinoids had occurred during the culture period. All-trans-retinoic acid was
      present in the embryos proper at quantitatively similar concentrations (20-100
      nM) after microinjections of the selected quantities of each of the microinjected
      retinoids: retinol, all-trans-retinoyl-beta-glucuronide, 13-cis-retinoic acid, or
      all-trans-retinoic acid. The results suggested that all-trans-retinoic acid acted
      as an ultimate dysmorphogen for the retinoids tested with respect to the
      anomalies monitored in the embryo culture system.

PMID- 1352214
TI  - Metabolism of sodium nifurstyrenate, a veterinary antimicrobial nitrofuran, in
      animals and fish.
AB  - Sodium nifursyrenate [beta-(5-nitro-2-furyl)-p-carboxystyrene sodium salt, NSA
      Na] is an antibacterial nitrofuran which has been widely used for prevention and
      treatment of bacterial infections in fish in Japan. When NSA-Na was anaerobically
      incubated with rabbit liver cytosol and 2-hydroxypyrimidine, 1-(p-carboxyphenyl)
      5-cyano-3-oxo-1,4-pentadiene (cyano-pentadienone), 1-(p-carboxyphenyl)-5-cyano-3
      oxo-1-pentanone (cyano-pentanone), and 1-(p-carboxyphenyl)-5-cyano-3-pentanone
      (cyano-pentanone) were isolated and identified as the metabolites of the
      nitrofuran. In addition, when cyano-pentenone and cyano-pentanone were
      aerobically incubated with the liver preparation and NADPH, 1-(p-carboxyphenyl)-5
      cyano-3-hydroxy-1-pentene (cyano-pentenol) and 1-(p-carboxyphenyl)-5-cyano-3
      pentanol (cyano-pentanol) were also isolated and identified as the metabolites of
      the nitrofuran in its further metabolism, respectively. The anaerobic incubation
      of NSA-Na with rat liver cytosol and 2-hydroxypyrimidine resulted in the
      formation of cyano-pentadienone and cyano-pentanone. In this case, however, cyano
      pentenone was not detectable. On the other hand, when NSA-Na was anaerobically
      incubated with sea bream liver cytosol and NADPH, the formation of cyano
      pentenone, cyano-pentanone, and cyanopentenol, but not cyano-pentadienone, was
      observed. Furthermore, cyano-pentanone was metabolized to cyano-pentanol by the
      fish liver preparation with NADPH under aerobic conditions. When NSA-Na was given
      orally to rabbits, cyano-pentanone, cyano-pentenol, cyano-pentanol, and beta
      (acetamido-2-furyl)-p-carboxystyrene (acetamidofuran) were identified as the
      urinary metabolites of the nitrofuran.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352215
TI  - Availability of glycine and coenzyme A limits glycine conjugation in vivo.
AB  - Using benzoic acid as substrate, this study tested the hypothesis that capacity
      limitation of glycine conjugation in vivo is due to substrate-induced depletion
      of hepatic cosubstrates (i.e., ATP, coenzyme A, and glycine) utilized in the
      conjugation reaction. Benzolyglycine formation was investigated by following the
      disappearance of benzoic acid from blood and appearance of benzoylglycine in
      blood and urine after administration of sodium benzoate (0.2-2 mmol/kg, iv) to
      anesthetized rats whose urine formation was stimulated by mannitol
      administration. Capacity limitation of glycine conjugation is indicated by (a)
      the gradual dose-dependent reduction of benzoate blood clearance from 39
      ml/min/kg at 0.2 mmol/kg benzoate to 3.7 ml/min/kg at 2 mmol/kg, and (b) the
      tendency to attain maximal blood levels and urinary excretion rates of
      benzoylglycine after administration of 0.5-1 mmol/kg benzoate. The maximal
      urinary excretion rate of benzoylglycine after benzoylglycine administration
      exceeded the maximal excretion rate of endogenously formed benzoylglycine
      (approximately 5 mumol/kg/min) 5-fold. This suggests that the urinary excretion
      rate of endogenously formed benzoylglycine reflects the rate of its formation.
      Benzoate depleted hepatic glycine (to 40%) and coenzyme A (to 14%) in a dose
      dependent fashion; however, it did not change ATP levels in liver. The pattern of
      this dose-dependent cosubstrate depletion suggests that benzoate primarily causes
      consumption of hepatic glycine which, at high substrate dosage, leads to marked
      depletion of coenzyme A in the liver. Thus, these observations indicate that
      capacity-limited glycine conjugation may be due to limited availability of
      glycine and coenzyme A for the conjugation process.

PMID- 1352216
TI  - Human hepatic microsomal metabolism of delta 1-tetrahydrocannabinol.
AB  - Hepatic microsomal metabolism of delta 1-tetrahydrocannabinol (THC) has been
      extensively studied in many rodent species, but there have been few reports
      describing such metabolism in humans. Because several THC metabolites are known
      to be pharmacologically active, identifying the P-450 subfamilies responsible for
      their formation is of clinical importance. We have found that, in addition to
      catalyzing the formation of significant amounts of 7-hydroxy-THC, hepatic
      microsomes from nine human livers also formed 6 beta-hydroxy-THC at approximately
      the same rate. In addition, 1 alpha,2 alpha-epoxyhexahydrocannabinol (EHHC) was
      formed at approximately one-third the rate of 7-hydroxy- and 6 beta-hydroxy-THC,
      and small amounts of 6 alpha-hydroxy- and 6-keto-THC were also found.
      Immunoinhibition studies with antibodies raised against human hepatic P-450 2C9,
      or a mouse hepatic P-450 isozyme belonging to the P-450 3A subfamily, revealed
      that P-450 2C9 catalyzed the formation of 7-hydroxy-THC, whereas P-450 3A
      catalyzed the formation of 6 beta-hydroxy-THC, EHHC, and the relatively minor
      metabolites. In contrast, antibodies raised against human P-450 2C8 had no affect
      on human microsomal THC hydroxylation. Excellent correlations were found between
      hepatic microsomal P-450 2C9 and 3A content and 7-hydroxy- and 6 beta-hydroxy-THC
      formation, respectively. In addition, purified P-450 2C9 catalyzed the formation
      of 7-hydroxy-THC at a 7-fold higher rate than that observed with microsomes.
      Microsomal 7-hydroxy-THC formation varied less than 5-fold between the livers,
      suggesting that this activity is normally expressed and probably not subject to
      environmental influences.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352217
TI  - Human hepatic microsomal thiol methyltransferase. Assay conditions, biochemical
      properties, and correlation studies.
AB  - Thiol methyltransferase (TMT) catalyzes the S-methylation of aliphatic sulfhydryl
      drugs and xenobiotic compounds. As a first step in the determination of whether
      genetic control of TMT activity in an easily accessible human cell, the red blood
      cell (RBC), might reflect the regulation of TMT in the human liver, we determined
      optimal conditions for the assay of human hepatic microsomal TMT activity. We
      then used those assay conditions to study the biochemical properties and
      regulation of TMT in the human liver for comparison with the properties of TMT in
      the human RBC. Substrate kinetic studies of hepatic microsomes performed with 2
      mercaptoethanol (2-ME) revealed biphasic kinetics similar to those found in the
      human RBC, with apparent "high-" and "low"-affinity forms of TMT activity. The
      high-affinity form had an optimal pH of 7.2-7.6 and apparent KM values of 9.0
      microM for 2-ME and 7.5 microM for S-adenosyl-L-methionine. The low-affinity form
      had an optimal pH of 8.8 and apparent KM values of 20 mM for 2-ME and 44 microM
      for S-adenosyl-L-methionine. Both forms were inhibited by compounds that also
      inhibited human RBC membrane TMT. The two kinetic forms of hepatic microsomal TMT
      activity were inactivated approximately 50% by heating for 15 min at 53 degrees C
      and, as was found with RBC TMT, had very similar thermal stability
      profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352218
TI  - Urinary metabolic profiles in human and rat of 1,2-dimethyl- and 1,2-diethyl
      substituted 3-hydroxypyridin-4-ones.
AB  - The urinary metabolic profiles of two novel orally active iron chelators, 1,2
      dimethyl-3-hydroxypyridin-4-one (CP20 or L1) and 1,2-diethyl-3-hydroxypyridin-4
      one (CP94), have been studied in rats. The metabolism of CP20 was also studied in
      humans. Four novel metabolites of CP20, and a further three metabolites of CP94
      were characterized. CP20 was found to undergo extensive phase II metabolism at
      the 3-hydroxy position, forming predominantly the O-glucuronide, which accounted
      for 44% of the dose administered in rat and greater than 85% of the dose
      administered in man. The 3-O-methylated CP20 metabolite (metabolite I) accounted
      for 1% of the administered dose in both species, whereas the unmetabolized CP20
      amounted to 10.5% and 4% of the dose administered in the rats and man,
      respectively. In contrast, CP94 was extensively hydroxylated at the 2-ethyl
      position to give its 2-(1-hydroxyethyl) metabolite in the rat, which accounted
      for 40% of the administered dose. The O-glucuronide metabolite of CP94 accounted
      for 13.8% of the administered dose, whereas the unmetabolized CP94 amounted to
      6.9% of the administered dose. At 72 hr, urinary levels of CP20 and CP94 and
      their metabolites in the rat accounted for about 55-60% of the administered dose.
      A large portion of the dose is therefore probably eliminated via the bile. The
      identity of the above metabolites was established using a combination of two or
      more of the following techniques: fast atom bombardment-mass spectroscopy, LC-MS,
      UV-VIS spectroscopy, NMR spectroscopy, specific enzyme hydrolysis assays, and
      chemical synthesis of compounds.

PMID- 1352219
TI  - A metabolic route of omeprazole involving conjugation with glutathione identified
      in the rat.
AB  - A metabolic route of omeprazole involving glutathione has been established
      through identification of endproducts excreted in the urine of rats after oral
      administration of 400 mumol/kg of a mixture of [3H]- and [14C]omeprazole. The
      labeled positions enabled facile tracing of metabolites that were formed through
      fission of omeprazole, producing [3H]pyridine and [14C]benzimidazole metabolites.
      The structures of the metabolites were established by HPLC thermospray MS and
      MS/MS. Two of the metabolites were isolated and characterized by 1H NMR studies.
      The fact that the N-acetylcysteine derivative of the benzimidazole was one of the
      endproducts indicated that the initial reaction involved glutathione. Three
      metabolites reflecting the fate of the pyridine moiety were identified. Their
      proposed formation route is via initial reduction to the pyridylmethylthiol
      compound followed by S-methylation and S-oxidation to the corresponding sulfoxide
      or sulfone. The quantity of metabolites formed via the glutathione route
      identified in urine was about 10% of the dose given, both in male and female
      rats. The male and female rats excreted the same cleaved metabolites and
      approximately equal quantities thereof.

PMID- 1352220
TI  - Stereoselective acetonyl side chain reduction of warfarin and analogs. Partial
      characterization of two cytosolic carbonyl reductases.
AB  - The reductase activity mediating the ketone reduction of the acetonyl side-chain
      of warfarin and analogs has been partially purified from rabbit liver cytosol.
      The reductase activity is resolved in two different fractions (A and B) by DEAE
      Sephacel chromatography. Both fractions reduce the acetonyl group of warfarin
      analogs with marked substrate (R-enantiomers), as well as product
      stereoselectivity (alcohols of the S-configuration). The reductases are NADPH
      dependent, which is absolute for fraction B. The enzyme kinetics of the R
      enantiomers of warfarin and three 4'-derivatives (4'-nitro-, 4'-chloro-, and 4'
      methoxywarfarin) has been investigated. In contrast to fraction B, fraction A is
      sensitive in its KM for 4' substitution: the KM values of 4'-nitro- and chloro
      analogs are approximately 6 times lower than the KM values of the 4'-methoxy
      analog or warfarin itself. On the other hand, the Vmax values of fraction A are
      all in the range of about 1 to 2 nmol/mg x min, whereas the Vmax values of
      fraction B vary from about 1(4'-methoxywarfarin) to 12 (the 4'-nitro analog). The
      intrinsic activities (Vmax/KM) of both enzymes show the same rank order: 4'-nitro
      greater than 4'-chloro greater than 4'-methoxy = warfarin. Warfarin reductase
      activity of both enzymes is not inhibited by pyrazole, sodium barbitone, or
      dicoumarol, but is strongly inhibited by quercetin, indomethacin, furosemide, and
      prostaglandin E2 (PGE2). In addition, fraction A is inhibited by menadione and
      androsterone; fraction B is inhibited by estrone. Various compounds were tested
      as substrates for these enzyme fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352221
TI  - Guinea pig and rat hepatic microsomal metabolism of monocrotaline.
AB  - The comparative metabolism of the pyrrolizidine alkaloid, [14C]monocrotaline, was
      studied using rat and guinea pig hepatic microsomes. Metabolites were quantified
      to the nanomole level using HPLC and radiometric detection.
      Triorthocresylphosphate and carbon monoxide were used to assess the involvement
      of carboxylesterases and cytochrome P-450 in the hepatic microsomal metabolism of
      monocrotaline, respectively. Esterase hydrolysis accounted for 92% of the
      metabolism in the guinea pig; the rat displayed no esterase activity. This result
      may explain the guinea pig's resistance to pyrrolizidine alkaloid toxicity.
      Dehydropyrrole was found to be the major pyrrolic metabolite in the guinea pig,
      although colorimetric analysis indicated multiple pyrrolic moieties in the rat
      microsomal incubations.

PMID- 1352222
TI  - The metabolism of DuP 753, a nonpeptide angiotensin II receptor antagonist, by
      rat, monkey, and human liver slices.
AB  - The in vitro metabolism of DuP 753, a novel nonpeptide angiotensin II receptor
      antagonist, has been investigated in incubations with liver slice preparations
      from rats, monkeys and humans. Metabolites were identified by HPLC/MS, FAB/MS,
      Cl/MS, and/or 1H NMR. In the rat, the primary route of metabolism was oxidative,
      leading to either monohydroxylated or oxidized (carboxylic acid) metabolites,
      whereas in monkeys, glucuronidation of the tetrazole moiety predominated. An
      equal mixture of both oxidized and glucuronic acid-conjugated metabolites was
      isolated from incubations with human liver slices. All metabolites were tested in
      an in vitro assay to determine their activity as angiotensin II receptor
      antagonists. The monohydroxylated products and glucuronic acid conjugates were
      determined to be much less active than DuP 753. Biotransformation to the
      carboxylic acid, however, was shown to dramatically increase the activity of this
      agent. The in vivo duration of action of DuP 753 has been observed to be much
      longer in the rat than in the monkey. This may be explained, at least in part, by
      these in vitro metabolism studies. The predominance of glucuronidation observed
      in incubations with monkey liver slices would yield metabolites with diminished
      activity and might be expected to shorten the in vivo duration of DuP 753 in that
      species. The oxidative conversion to the carboxylic acid metabolite, along with
      the low level of glucuronidation observed in incubations with rat liver slices,
      may be responsible for the prolonged duration observed in vivo in the rat.

PMID- 1352223
TI  - The influence of vitamin K3 treatment on the pharmacokinetics and metabolism of
      (+)-propranolol in the rat.
AB  - The effects of vitamin K3 treatment on the pharmacokinetics and metabolism of (+)
      propranolol and the consequences of hepatic injury associated with vitamin K3
      treatment were examined in groups of male Sprague-Dawley rats. When vitamin K3
      (20 mg/kg) in polyethylene glycol 300 (PEG 300) was coinfused with (+)
      propranolol (2 mg/kg) into the pyloric vein (a tributary flowing directly into
      the hepatic portal vein), a significant decrease in the intrinsic clearance of
      total drug (CLint) from 94.1 +/- 50.1 to 32.9 +/- 11.5 ml/min/kg was observed (p
      less than 0.01 vs. vehicle control). However, a lower dose of vitamin K3 (2 mg/kg
      in PEG 300) had little effect on this parameter. Interestingly, the PEG 300
      vehicle control group exhibited a significantly (p less than 0.05) higher CLint
      than that observed in a saline control group (94.1 +/- 50.1 vs. 45.9 +/- 13.7
      ml/min/kg). This difference appeared to be due to an increase in the free
      fraction of propranolol caused by PEG 300, because in vitro addition of this
      solvent to serum (at estimated in vivo concentrations) with or without added
      vitamin K3 doubled propranolol free fraction. Furthermore, rats that received the
      high dose vitamin K3 (20 mg/kg) treatment exhibited a pronounced increase in the
      serum concentration of enzymes of hepatic origin (alanine aminotransferase and
      sorbitol dehydrogenase) and in the incidence of hepatic necrosis. It was also
      observed that high-dose vitamin K3 treatment caused only minor changes in the
      urinary recovery of propranolol metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352224
TI  - Metabolic fate of menthofuran in rats. Novel oxidative pathways.
AB  - Metabolic fate of menthofuran (II) in rats was investigated. Menthofuran (II) was
      administered orally (200 mg/kg of the body weight/day) to rats for 3 days. The
      following metabolites were isolated from the urine of these animals: p-cresol
      (VI), 5-methyl-2-cyclohexen-1-one (VII), 3-methylcyclohexanone (VIII), 3
      methylcyclohexanol (IX), 4-hydroxy-4-methyl-2-cyclohexen-1-one (V), geranic acid
      (XI), neronic acid (XII), benzoic acid (XIII), and 2-[2'-keto-4'
      methylcyclohexyl]propionic acid (X). Incubation of menthofuran (II) with
      phenobarbital-induced rat liver microsomes in the presence of NADPH and oxygen
      resulted in the formation of a metabolite tentatively identified as 2-Z-(2'-keto
      4'-methylcyclohexylidene)propanal (III; alpha,beta-unsaturated-gamma-keto
      aldehyde). The structure assigned was further supported by trapping this
      metabolite (III) as a cinnoline derivative. Phenobarbital-induced rat liver
      microsomes also converted 4-methyl-2-cyclohexenone (IV) to 4-hydroxy-4-methyl-2
      cyclohexenone (V) and p-cresol (VI) in the presence of NADPH and oxygen. On the
      basis of both in vivo and in vitro studies, a possible mechanism for the
      formation of p-cresol from menthofuran has been proposed.

PMID- 1352225
TI  - Pharmacokinetics of caffeine and its demethylated metabolites in lactating adult
      rabbits and neonatal offspring. Predictions of breast milk to serum concentration
      ratios.
AB  - The purpose of this study was to assess the pharmacokinetics of caffeine and its
      metabolites in the lactating rabbit and suckling pup. The ability of a
      diffusional model to predict milk-to-serum drug concentration ratios (M/S)
      observed in vivo from in vitro experiments was established. The distribution into
      milk of caffeine, paraxanthine, theobromine, and theophylline was measured in
      lactating New Zealand White rabbits following an iv bolus dose of caffeine (5
      mg/kg). M/S ratios were determined in vivo (M/Sobs; caffeine = 0.875 +/- 0.052;
      paraxanthine = 0.358 +/- 0.019; theobromine = 0.829 +/- 0.038; and theophylline =
      0.412 +/- 0.054) under single dose conditions using area under the milk and serum
      concentration-time profiles. Predicted M/S values (M/Spred; caffeine = 0.797 +/-
      0.040; paraxanthine = 0.316 +/- 0.029; theobromine = 0.692 +/- 0.062; and
      theophylline = 0.385 +/- 0.039) were calculated from in vitro measurements of the
      unbound fractions of drug in skim milk and serum (fm and fs, respectively), the
      skim-to-whole milk drug concentration ratio (S/W), milk and serum pH, and the pKa
      of the model compound. The pharmacokinetic profile of caffeine in the suckling
      pup following iv bolus administration (5 mg/kg) was more prolonged compared with
      adult rabbits. The mean systemic clearance of total caffeine (CIs) in the adults
      and the pups was 3.83 +/- 1.94 and 1.14 +/- 0.80 ml/min/kg, respectively. The
      mean unbound systemic clearance (CIs,u) for caffeine was 5.09 +/- 2.60 ml/min/kg
      in the adults and 1.41 +/- 0.71 ml/min/kg in the pups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1352227
TI  - Involvement of the cytochrome P-450IID subfamily in minaprine 4-hydroxylation by
      human hepatic microsomes.
AB  - 4-Hydroxylation of minaprine was measured on microsomal fractions prepared from
      25 different human liver samples. In vitro formation of 4-hydroxyminaprine
      exhibited a large interindividual variability. Indeed, minaprine 4-hydroxylase
      activity ranged between 0.033 and 0.421 nmol/min/mg microsomal protein. Two
      samples presented a particularly low enzyme activity. Minaprine 4-hydroxylation
      followed Michaelis-Menten kinetics with KM and Vmax values of 5.26 microM and
      0.478 nmol/min/mg microsomal protein, respectively, for one particular
      representative sample. The effects of various compounds (substrates or inhibitors
      of cytochrome P-450 isoforms) on 4-hydroxyminaprine formation were investigated.
      Selective substrates for P-450IA [benzo(a)pyrene, theophylline, and phenacetin],
      IIC (hexobarbital), IIE (aniline), and IIIA (erythromycin, nifedipine, and
      troleandomycin) cytochrome subfamilies did not inhibit 4-hydroxyminaprine
      formation. The nonspecific cytochrome P-450 inhibitor, cimetidine, slightly
      inhibited minaprine 4-hydroxylation. The classical substrates of the P-450IID
      cytochrome subfamily (debrisoquine, propranolol, and sparteine) inhibited
      minaprine 4-hydroxylation, as did the known P-450IID specific inhibitor,
      quinidine. These compounds inhibited minaprine 4-hydroxylase with Ki values of
      16.5 (debrisoquine), 14.4 (propranolol), 61.9 (sparteine), and 0.146 microM
      (quinidine). 4-Hydroxyminaprine formation rate was shown not to be correlated
      with the activity of both erythromycin N-demethylase (r = 0.29, non-significant)
      and aniline hydroxylase (r = -0.15, NS). In contrast, minaprine 4-hydroxylase was
      well correlated with both debrisoquine 4-hydroxylase activity (r = 0.501, p less
      than 0.05) and immunoquantified cytochrome P-450IID6 (r = 0.579, p less than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352226
TI  - Alpha-glucoside formation of xenobiotics by rat liver alpha-glucosidases.
AB  - We investigated enzymes participating in alpha-glucoside formation, a novel
      metabolic pathway of xenobiotics in a metabolic study of indeloxazine
      hydrochloride in rats. When rat tissue homogenates and the indeloxazine
      metabolite trans-4-(2-morpholinylmethoxy)-1,2-indandiol (M-2) were incubated, M-2
      alpha-glucoside formation was observed in liver. This reaction was almost
      completely inhibited by the alpha-glucosidase inhibitor acarbose. The liver
      homogenate was then separated into subcellular fractions and an acid alpha
      glucosidase in lysosomes and two neutral alpha-glucosidases in microsomes and
      cytosol were partially purified. The chromatographic behavior and optimum pH of
      the glucosyltransferase activity of each of the enzyme preparations were almost
      identical with those of alpha-glucosidase (hydrolase) activity of the same
      specimen, suggesting the former activity to be also due to alpha-glucosidase.
      Agreeing with their hydrolytic substrate specificities, the acid enzyme
      transferred glucose to M-2 from a series of glucose derivatives, ranging from low
      molecular maltosaccharides to high molecular glycogen, whereas the neutral
      enzymes took only low molecular maltosaccharides as glucosyl donors. These
      results led to the conclusion that the formation of alpha-glucoside conjugates is
      catalyzed by more than one alpha-glucosidase in the liver and uses
      maltosaccharides or glycogen as glucosyl donors. Several other diol structure
      bearing compounds were found in vitro to give rise to alpha-glucoside conjugates,
      and the mechanism of alpha-glucoside formation is discussed.

PMID- 1352228
TI  - Metabolic inversion of (R)-ibuprofen. Epimerization and hydrolysis of ibuprofenyl
      coenzyme A.
AB  - Ibuprofen [(racemic)2-(4-isobutylphenyl)propionic acid] has been proposed but not
      directly demonstrated to undergo unidirectional inversion from the (R)- to the
      (S)-configuration via a coenzyme A (CoA) thioester intermediate. Chemically
      synthesized (R)- and (S)-ibuprofenyl-CoA, and rat and human liver homogenates
      were used to investigate the relative rates of ibuprofenyl-CoA epimerization and
      hydrolysis. Rat whole liver homogenate completely epimerized (R)- or (S)
      ibuprofenyl-CoA, whereas hydrolysis of this intermediate occurred at a much
      slower rate. Rat liver mitochondria was the most efficient at both epimerizing
      and hydrolyzing ibuprofenyl-CoA, whereas rat liver microsomes hydrolyzed
      ibuprofenyl-CoA at a rate similar to whole liver homogenate but had very little
      epimerization activity. Rat liver cytosol was the poorest at hydrolyzing
      ibuprofenyl-CoA but had substantial epimerization capability. Whole liver
      homogenate from human tissue was less efficient at epimerizing but as efficient
      at hydrolyzing ibuprofenyl-CoA as rat whole liver homogenate. No
      stereoselectivity of either epimerization or hydrolysis was noted for any of the
      enzyme preparations studied. This study demonstrates that the inversion of (R)
      ibuprofen occurs, at least in part, via the epimerization of the metabolic
      intermediate, ibuprofenyl-CoA, in both rat and human liver tissues.

PMID- 1352229
TI  - Glucuronidation of zileuton (A-64077) by human hepatic microsomes.

PMID- 1352230
TI  - New evidence of sparteine metabolites in humans.

PMID- 1352232
TI  - Carboxyphosphamide: NMR studies of its stability and cell membrane permeability.

PMID- 1352231
TI  - Stereoselective sulfate conjugation of 4-hydroxypropranolol and terbutaline by
      the human liver phenolsulfotransferases.

PMID- 1352233
TI  - Interactions of a primary N-hydroxy arylamine with rat hepatic aryl
      sulfotransferase IV.

PMID- 1352234
TI  - [Receptor scintigraphy in endocrine gastrointestinal and pancreatic tumors].

PMID- 1352235
TI  - [Therapy of endocrine gastrointestinal-pancreatic tumors with somatostatin analog
      octreotide].

PMID- 1352236
TI  - Molecular analysis of the deletion mutants in the E homeotic complex of the
      silkworm Bombyx mori.
AB  - The E loci in Bombyx mori are expected to contain a homeotic gene complex
      specifying the identities of the larval abdominal segments. However, the
      molecular structure of this complex remains to be determined. We have started to
      analyze the structural changes in the E complex mutations. We used three newly
      isolated Bombyx homeobox genes as probes. These genes are probably homologues of
      the Ultrabithorax (Ubx), abdominal-A (abd-A) and Abdominal-B (Abd-B) in the
      Drosophila bithorax complex, because the amino-acid sequences of the homeobox
      regions in these Bombyx genes are almost identical to those of Drosophila genes.
      We found that the Bombyx Ubx and abd-A genes are deleted in the EN chromosome,
      and the Bombyx abd-A gene is deleted in the ECa chromosome. From these results,
      we conclude that the Bombyx E complex consists of the Ubx, abd-A and possibly Abd
      B genes, which may play similar roles to their homologues in the Drosophila
      bithorax complex.

PMID- 1352237
TI  - SUPERMAN, a regulator of floral homeotic genes in Arabidopsis.
AB  - We describe a locus, SUPERMAN, mutations in which result in extra stamens
      developing at the expense of the central carpels in the Arabidopsis thaliana
      flower. The development of superman flowers, from initial primordium to mature
      flower, is described by scanning electron microscopy. The development of doubly
      and triply mutant strains, constructed with superman alleles and previously
      identified homeotic mutations that cause alterations in floral organ identity, is
      also described. Essentially additive phenotypes are observed in superman agamous
      and superman apetala2 double mutants. The epistatic relationships observed
      between either apetala3 or pistillata and superman alleles suggest that the
      SUPERMAN gene product could be a regulator of these floral homeotic genes. To
      test this, the expression patterns of AGAMOUS and APETALA3 were examined in
      superman flowers. In wild-type flowers, APETALA3 expression is restricted to the
      second and third whorls where it is required for the specification of petals and
      stamens. In contrast, in superman flowers, APETALA3 expression expands to include
      most of the cells that would normally constitute the fourth whorl. This ectopic
      APETALA3 expression is proposed to be one of the causes of the development of the
      extra stamens in superman flowers. The spatial pattern of AGAMOUS expression
      remains unaltered in superman flowers as compared to wild-type flowers. Taken
      together these data indicate that one of the functions of the wild-type SUPERMAN
      gene product is to negatively regulate APETALA3 in the fourth whorl of the
      flower. In addition, superman mutants exhibit a loss of determinacy of the floral
      meristem, an effect that appears to be mediated by the APETALA3 and PISTILLATA
      gene products.

PMID- 1352238
TI  - Sequence and expression pattern of pax-6 are highly conserved between zebrafish
      and mice.
AB  - Despite obvious differences in the patterns of early embryonic development,
      vertebrates share a number of developmental mechanisms and control genes,
      suggesting that they use similar genetic programs at some stages of development.
      To examine this idea, we isolated and characterized one such gene, pax-6, a
      member of the pax gene family, from the zebrafish Brachydanio rerio and
      determined the evolutionary conservation in the structure and expression of this
      gene by comparison to its homolog in mice. We found two alternatively spliced
      forms of the zebrafish pax-6 message. Sequence and expression pattern of the
      zebrafish pax-6 gene are remarkably similar to its murine homolog. pax-6
      expression begins during early neurulation. A stripe of cells in the
      neuroectoderm, including the prospective diencephalon and a part of the
      telencephalon, expresses pax-6 as well as the hindbrain and the ventral spinal
      cord extending from the level of the first rhombomere to the posterior end of the
      CNS. During later development more limited regions of the brain including the
      eye, the olfactory bulb and the pituitary gland express pax-6. Cells at the
      midbrain-hindbrain junction express eng genes and are separated from the
      neighboring pax-6 regions by several cells that express neither gene, indicating
      a complex subdivision of this region. pax-6 expression appears during processes
      when cell-to-cell signalling is thought to be important, for example during
      induction of the eye and regionalization of the spinal cord and brain, suggesting
      that it may be one component mediating the response to inductive interactions.

PMID- 1352239
TI  - An early marker of axial pattern in the chick embryo and its respecification by
      retinoic acid.
AB  - Chick Ghox 2.9 protein, a homeodomain-containing polypeptide, is first detected
      in the mid-gastrula stage embryo and its levels increase rapidly in the late
      gastrula. At this time, the initially narrow band of expression along the
      primitive streak expands laterally to form a shield-like domain that encompasses
      almost the entire posterior region of the embryo and extends anteriorly as far as
      Hensen's node. We have found that this expression domain co-localizes with a
      morphological feature that consists of a stratum of refractile, thickened
      mesoderm. Antibody-staining indicates that Ghox 2.9 protein is present in all
      cells of this mesodermal region. In contrast, expression within the ectoderm
      overlying the region of refractile mesoderm varies considerably. The highest
      levels of expression are found in ectoderm near the streak and surrounding
      Hensen's node, regions that recent fate mapping studies suggest that primarily
      destined to give rise to neurectoderm. At the definitive streak stage (Hamburger
      and Hamilton stage 4) the chick embryo is especially sensitive to the induction
      of axial malformations by retinoic acid. Four hours after the treatment of
      definitive streak embryos with a pulse of retinoic acid the expression of Ghox
      2.9 protein is greatly elevated. This ectopic expression occurs in tissues
      anterior to Hensen's node, including floor plate, notochord, presumptive neural
      plate and lateral plate mesoderm, but does not occur in the anteriormost region
      of the embryo. The ectopic induction of Ghox 2.9 is strongest in ectoderm, and
      weaker in the underlying mesoderm. Endoderm throughout the embryo is
      unresponsive. At stage 11, Ghox 2.9 is normally expressed at high levels within
      rhombomere 4 of the developing hindbrain. In retinoic-acid-treated embryos which
      have developed to this stage, typical rhombomere boundaries are largely absent.
      Nevertheless, Ghox 2.9 is still expressed as a discrete band, but one that is
      widened and displaced to a more anterior position.

PMID- 1352240
TI  - Function of an Ultrabithorax minigene in imaginal cells.
AB  - An Ultrabithorax (Ubx) minigene constructed from three key Ubx control regions is
      capable of supporting development of Ubx null mutants throughout larval life and
      beyond to pharate flies, thereby rescuing the larval lethality due to the
      homeotic mutation. The cuticle of these flies shows that the minigene provides at
      least partial Ubx function in each of the four compartments whose morphogenetic
      pathways are determined by Ubx. We analyse beta-galactosidase patterns in
      imaginal discs conferred by each individual Ubx control region. From the
      comparison of these patterns with Ubx expression in Cbx mutants, we infer that
      long-range repressor elements in the chromosomal Ubx gene play an important role
      in the generation of Ubx expression patterns in imaginal discs. Expression and
      function of our Ubx minigenes indicate that Ubx control regions are capable of
      functioning properly out of context and detached from their normal chromosomal
      location within the homeotic gene complex.

PMID- 1352241
TI  - The mouse has a Polycomb-like chromobox gene.
AB  - The Drosophila gene Polycomb (Pc) has been implicated in the clonal inheritance
      of determined states and is a trans-regulator of the Antennapedia-like homeobox
      genes. Pc shares a region of homology (the chromobox) with the Drosophila gene
      Heterochromatin Protein 1 (HP1), a component of heterochromatin. The Pc chromobox
      has been used to isolate a mouse chromobox gene, M33, which encodes a predicted
      519 amino acid protein. The M33 chromodomain is more similar to that in the Pc
      protein, than that in the HP1 protein. In addition to the chromodomain, the M33
      and Pc proteins also share a region of homology at their C termini. The temporal
      and spatial expression patterns of M33 have been studied by in situ hybridization
      and northern analysis. During the final 10 days of embryonic development, M33
      expression mirrors that of the cell-cycle-specific cyclin B gene. It is therefore
      suggested that the rate of cellular proliferation controls M33 expression. From
      comparisons of the characteristics of M33 with those of Pc it is proposed that
      M33 is a Pc-like chromobox gene. The roles of M33 and Pc in models of cellular
      memory are examined and implications of the memory models addressed.

PMID- 1352242
TI  - The mis-expression of posterior Hox-4 genes in talpid (ta3) mutant wings
      correlates with the absence of anteroposterior polarity.
AB  - Developing chicken wings homozygous for the talpid (ta3/ta3) mutation are
      polydactylous and have defects in the establishment of their anteroposterior
      polarity. We analysed the expression domains of the posteriorly restricted
      homeobox Hox-4 genes in such mutant wings. The Hox-4 genes are now expressed
      right across the anteroposterior axis instead of being expressed just
      posteriorly. This correlates well with the absence of clear morphological
      differences between the talpid3 digits and reinforces the idea that vertebrate
      Hox-4 genes are involved in setting up the limb anteroposterior asymmetry.

PMID- 1352243
TI  - Dopamine agonists and pituitary tumor shrinkage.
AB  - The primary aim of this review has been to clarify the tumor shrinking effects of
      dopamine agonists on pituitary macroadenomas of different cell types. Shrinkage
      is most dramatic for macroprolactinomas and is due to cell size reduction.
      Seventy-nine percent of 271 definite macroprolactinomas were reduced in size by
      at least 25%, and 89% shrank to some degree. Most shrinkage occurs during the
      first 3 months of treatment, although in a minority shrinkage is delayed.
      Dopamine agonist resistance during long-term therapy is exceptional. Drug
      withdrawal nearly always leads to a return of hyperprolactinemia, even after
      several years treatment, although early tumor reexpansion is unusual. About 10%
      of true macroprolactinomas do not shrink with dopamine agonists; the molecular
      mechanisms of such resistance have yet to be determined. Alternative formulations
      of BC and new dopamine agonists (CV 205-502 and cabergoline) are useful for the
      minority of patients unable to tolerate oral BC, but do not seem to further
      improve overall shrinkage rates. The risks of pregnancy have probably been
      overstated, and BC is suitable primary treatment for women with prolactinomas of
      all sizes; the drug can be used safely during pregnancy in the event of
      clinically relevant tumor expansion. The interpretation of different degrees of
      hyperprolactinemia is discussed and management strategies suggested. Most
      patients with macroprolactinomas now avoid surgery, but drug-induced, time
      dependent tumor fibrosis should be remembered if surgery is contemplated.
      Nonfunctioning pituitary tumors are mostly of gonadotroph cell origin and may be
      associated with significant disconnection hyperprolactinaemia. Seventy-six of 84
      well-characterized tumors showed no tumor shrinkage during dopamine agonist
      therapy. Possible explanations include abnormalities of dopamine receptor number
      and function. Preliminary evidence suggests that dopamine agonists may restrain
      the growth of some functionless tumors; most of these tumors, however, can be
      satisfactorily debulked using transsphenoidal surgery. In contrast to
      macroprolactinomas, other functioning pituitary tumors (GH-, TSH-, and ACTH
      secreting) rarely shrink during dopamine agonist therapy, although the number of
      tumors studied is small.

PMID- 1352244
TI  - Basic counterpoint: mechanisms and pathways of gonadal steroid modulation of
      growth hormone secretion.
AB  - In spite of the different patterns of GH secretion observed in male and female
      rats, it can be argued that there are limited differences between the mechanism
      of action of androgens and estrogens as reported in the literature. However, we
      feel that it is possible to organize the available data into a unique
      physiological model explaining the sex-based differences in GH secretion in the
      rat. Thus, it can be proposed that the greater spontaneous GH peaks observed in
      the male with respect to the female rat may be due to an androgen-mediated
      enhancement of both GHRH secretion at the hypothalamic level and GH secretion at
      the pituitary level. The lower GH troughs observed in the male as compared to the
      female rat may be due to increased interpeak somatostatin secretion induced by
      the androgens with respect to the estrogens. It is likely that these high GH
      peaks and low GH troughs establish a recycling mechanism through established
      feedback mechanisms. That is, the high GH peak, induced by GHRH, stimulates
      somatostatin secretion such that a very low GH trough follows. In turn, this low
      GH trough, in the high somatostatin environment, establishes the correct
      neuroendocrine milieu for the next high GH peak, and so on. Additional studies
      will help clarify this model and hopefully provide a better understanding of the
      mechanisms regulating the interaction between gonadal steroids and GH.

PMID- 1352245
TI  - Is xamoterol safe in chronic airflow obstruction?
AB  - We have demonstrated in a group of 10 patients with CAO that treatment with
      xamoterol (200 mg b.i.d. for 7 days) did not alter lung function or respiratory
      symptoms. These results suggest that xamoterol can be used to treat mild heart
      failure in patients with CAO.

PMID- 1352246
TI  - Neuroendocrine effects of ipsapirone on the hypothalamic-pituitary adrenal axis:
      CRF, ACTH and cortisol in healthy volunteers.
AB  - The neuroendocrine effects (changes in plasma CRF, ACTH and cortisol) of single
      and multiple (t.d.s. for 2 days) doses of ipsapirone (BAY Q 7821) 5 and 10 mg
      have been investigated in 6 healthy male volunteers. The study followed a
      balanced complete block, placebo-controlled and double blind design with two
      baseline phases (pre and post-treatment). Volunteers were investigated on
      identical days during 5 successive weeks. The results do not show a specific
      effect of ipsapirone on the hypothalamic-pituitary-adrenal axis when doses in the
      range of 5-30 mg per day were given.

PMID- 1352248
TI  - The effect of ethanol on responses of the isolated rabbit ileocolic artery.
AB  - Antagonist drugs were used to separate the purinergic and adrenergic
      contributions involved in the sympathetic vasopressor responses produced by
      electrical field stimulation in the ileocolic artery of the rabbit. Blocking
      drugs were applied either alone or in various combinations and sequences. The
      effect of ethanol was studied in conditions of alpha-adrenoceptor blockade, P2x
      purinoceptor desensitisation, or in the absence of antagonists. From these
      studies it is concluded that ethanol has a selective potentiating effect on alpha
      adrenoceptor-mediated responses.

PMID- 1352247
TI  - Azelastine reduces allergen-induced nasal response: a clinical and
      rhinomanometric assessment.
AB  - The effect of azelastine 2 mg b.d. p.o. for 10 days on grass pollen-induced nasal
      responses in 16 patients with grass pollen allergic rhinitis has been assessed.
      The study was a double blind, randomized, placebo controlled, crossover trial,
      with a 10-14 day wash-out period. Patients were challenged with grass pollen
      before and after placebo and azelastine. The response was assessed by measurement
      of nasal resistance using active posterior rhinomanometry, by weighing nasal
      secretions, and by counting sneezes. The sensation of nasal obstruction was
      assessed with a visual analogue scale. After measurement of baseline total nasal
      resistance, doubling doses of allergen were sprayed into both nostrils at 15 min
      intervals until the nasal resistance was doubled. Cumulative doses of allergen
      that doubled prechallenge nasal resistance, numbers of sneezes and the amounts of
      nasal secretions were similar before azelastine as well as before and after
      placebo (cumulative dose, mean, (microgram): 2.3, 4.2 and 2.1 respectively,
      N.S.). After azelastine, the cumulative dose of allergen was increased (7.3
      micrograms), and nasal secretions and the number of sneezes were decreased. The
      visual analogue scores were similar before and after azelastine as well as before
      and after the placebo. It is concluded that azelastine reduced the allergen
      induced nasal responses.

PMID- 1352249
TI  - Different effects of peptidase inhibitors on dermorphin- and on [D
      Arg2]dermorphin-induced antinociceptive activity.
AB  - The antinociceptive effects produced by the intracerebroventricular (i.c.v.)
      injection of dermorphin and [D-Arg2]dermorphin were compared in conscious mice,
      using the combined administration of peptidase inhibitors. Nociception was
      assessed using a tail pressure assay. Dermorphin-induced antinociception was not
      potentiated by simultaneous administration of amastatin or captopril as judged
      from the ED50 values. Co-administration of dermorphin and amastatin gave a longer
      duration than with dermorphin alone, whereas there was no significant effect on
      duration with captopril. The antinociceptive activity of dermorphin was
      significantly enhanced when the heptapeptide was injected simultaneously with
      both peptidase inhibitors. This result indicates that the heptapeptide sequence
      is required for the full expression of intrinsic opioid activity of dermorphin.
      In contrast, co-administration of amastatin brought about a significant
      enhancement of the antinociceptive activity induced by i.c.v. administration of
      [D-Arg2]dermorphin, whereas the effect of [D-Arg2]dermorphin was markedly
      decreased by the concurrent administration of captopril or thiorphan. The potency
      of captopril was much greater than that of thiorphan. The present results suggest
      that [D-Arg2]dermorphin may be transformed metabolically to a peptide which has
      potent antinociceptive activity.

PMID- 1352251
TI  - Effects on body temperature in mice differentiate between dopamine D2 receptor
      agonists with high and low efficacies.
AB  - The effects of different dopamine (DA) D2 receptor agonists and the DA D2
      receptor antagonist, emonapride, on body temperature were studied in male mice.
      The aim of the study was to test whether DA D2 receptor agonists ranging from
      full agonists to agonists with low efficacy could be differentiated by means of
      their effect on body temperature. Talipexole induced a marked hypothermia
      (maximum decrease of 6.5 degrees C). Apomorphine, quinelorane, (+)-4-propyl-9
      hydroxy-naphtoxazine((+)-PHNO), and (-)-N-n-propylnorapomorphine ((-)-NPA)
      induced a maximum hypothermia of 3.5-4.1 degrees C. Quinpirole and (+)-3-(3
      hydroxyphenyl)-N-n-propylpiperidine ((+)-3-PPP) induced a less pronounced
      hypothermia (1.7 and 1.5 degrees C), and preclamol ((-)-3-PPP), terguride and 3
      (4-(4-phenyl-1,2,3,6-tetrahydropyridyl)-(1))-butyl)-indole (EMD 23448) had no or
      only a slight effect. Emonapride induced significant hyperthermia at high doses.
      Apomorphine-, quinelorane- and talipexole-induced hypothermia was reversed by
      terguride and preclamol, whereas EMD 23448 partially reversed the apomorphine
      induced hypothermia. The alpha 2-adrenoceptor antagonist, idazoxan, partly
      reversed the effect of talipexole. Quinpirole had no effect on the hypothermic
      effect of the above-mentioned agonists. Pretreatment with the catecholamine
      synthesis inhibitor, alpha-methyl-m-tyrosine, increased significantly the
      hypothermic response to quinpirole, whereas the effect of quinelorane was
      unchanged. It is suggested that the effect of DA D2 agonists on body temperature
      in mice can be used to differentiate between agonists with different
      efficacies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352250
TI  - The effect of some alpha-adrenoceptor antagonists on spontaneous myogenic
      activity in the rat portal vein and the putative involvement of ATP-sensitive K+
      channels.
AB  - In the present study we showed that the alpha-adrenoceptor antagonists
      phentolamine, yohimbine, prazosin, corynanthine and idazoxan, when cumulatively
      applied in high concentrations (1-100 mumol/l), can increase spontaneous myogenic
      activity in the rat portal vein. 5-Methyl-urapidil and rauwolscine were
      ineffective in this respect. Pretreatment with phenoxybenzamine in a
      concentration of 1 mumol/l (20 min), which results in alkylation of all
      functional alpha-adrenoceptors in the rat portal vein, was unable to antagonize
      the increase in spontaneous myogenic activity elicited by phentolamine.
      Antazoline (1-100 mumol/l), a H1 antagonist and 2-substituted imidazoline which
      is devoid of alpha-adrenoceptor blocking properties, exhibited similar effects on
      spontaneous myogenic activity as its structurally closely related analogue
      phentolamine. Since phentolamine is reported to interact with ATP-sensitive K+
      channels we investigated the role of K+ channels in more detail. The K+ channel
      openers cromakalim and diazoxide elicited a decrease in spontaneous myogenic
      activity. Glibenclamide (0.3-3 mumol/l), a selective blocker of ATP-sensitive K+
      channels in cardiac and pancreatic tissues, and phentolamine (1-10 mumol/l)
      shifted the concentration-response curves of cromakalim and diazoxide
      concentration dependently to the right. Yohimbine showed only a modest effect in
      the highest concentration (100 mumol/l) applied. E-4031 (0.01-0.3 mumol/l), a
      sotalol derivative and one of the most selective blockers of the delayed
      rectifier current (Ik) in cardiac tissue, was a potent contractile agent when
      added to the rat portal vein in the same way as the alpha-adrenoceptor
      antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352252
TI  - Persistent supersensitivity of sigma receptors develops during repeated
      methamphetamine treatment.
AB  - Functional changes in sigma receptors were examined after behavioral
      sensitization induced by repeated methamphetamine treatment. Rats received either
      saline or 4 mg/kg methamphetamine for 14 days. (+)3-(3-hydroxyphenyl)-N-(1
      propyl)piperidine ((+)-3-PPP), a sigma receptor agonist, was given as challenge
      after various periods of abstinence. (+)-3-PPP at doses greater than 6 mg/kg
      stimulated several forms of behavior in naive rats. (+)-3-PPP at 12 and 24 mg/kg
      produced more frequent rearing and more intense stereotyped sniffing and
      repetitive head movements in rats previously sensitized with methamphetamine than
      in saline-pretreated rats. The augmented response to (+)-3-PPP in methamphetamine
      treated rats was maintained for at least one month. The augmented response to (+)
      3-PPP was reversed by the combined administration of 100 mg/kg (+/-)-sulpiride, a
      D2 dopamine receptor antagonist, and 30 mg/kg BMY 14802, a sigma receptor
      antagonist. These results suggest that repeated methamphetamine treatment induces
      persistent supersensitivity in sigma receptors and that it may subsequently
      activate the dopamine system.

PMID- 1352253
TI  - Haemodynamic and humoral effects of omega-conotoxin GVIA in normotensive and
      spontaneously hypertensive rats.
AB  - Omega-conotoxin GVIA, a 27-amino acid peptide, has been shown to be a potent and
      selective inhibitor of N-type voltage-operated calcium channels (VOCCs). A single
      intravenous dose of 10 micrograms/kg conotoxin slowly lowered blood pressure by
      41.3 +/- 4.4 and 73.3 +/- 4.6 mm Hg in conscious Wistar-Kyoto rats (WKY) and
      spontaneously hypertensive rats (SHR) respectively without changing the heart
      rate. Plasma renin activity was significantly increased after conotoxin. In
      anaesthetized rats, conotoxin (3 and 10 micrograms/kg) lowered blood pressure and
      heart rate and produced a marked increase in renal vascular conductances.
      Baroreceptor heart rate reflex experiments using methoxamine and sodium
      nitroprusside before and after treatment with conotoxin showed that conotoxin
      almost totally abolished the sympathetic component of the reflex without
      affecting the vagal tone to the heart in both rat strains. Because conotoxin does
      not affect directly the vasculature and heart contractile properties, we suggest
      that the control of presynaptic calcium influx and of neurotransmitter release
      mostly depends on conotoxin-sensitive N-type VOCCs in the peripheral sympathetic
      system of the rat.

PMID- 1352254
TI  - Membrane stabilizing activity and beta-adrenoceptor antagonist-induced
      bradycardia in conscious dogs.
AB  - The atrial effective refractory period (AERP) and atrial and ventricular
      chronotropic effects of the stereoisomers of propranolol, pindolol, metoprolol
      and penbutolol were studied in conscious atrio-ventricular blocked dogs. Atrial
      beta-adrenoceptor blocking activity was assessed for all the drugs against
      isoprenaline. All the drugs except dextro-pindolol lengthened AERP and decreased
      ventricular rate dose relatedly. At comparable levels of atrial beta-adrenoceptor
      blockade, dextro-propranolol, dextro-metoprolol and dextro-penbutolol were more
      potent to induce AERP lengthening than their respective levo-isomers, whereas
      dextro-pindolol was less potent than levo-pindolol. In addition, levo-pindolol
      and levo-metoprolol were more potent to produce ventricular bradycardia than the
      corresponding dextro-isomers, whereas the levo- and dextro-isomers of propranolol
      and penbutolol were equipotent. These results confirm that the ventricular
      bradycardia induced by the different beta-adrenoceptor antagonists is partly due
      to ventricular beta-adrenoceptor blockade and to the membrane stabilizing
      activity of these drugs, and partly to another as yet unknown factor seen
      especially with the levo-isomers and particularly marked with metoprolol.

PMID- 1352255
TI  - Effect of atrial natriuretic peptide on apomorphine-induced stereotyped cage
      climbing behavior in mice.
AB  - In previous experiments, it was observed that rat atrial natriuretic peptide-(1
      28) (ANP-(1-28)) participated in fear-induced learning and memory processes via
      dopaminergic and cholinergic mediation. Since cage-climbing behavior is described
      as a simple test for studying dopaminergic activity in the central nervous
      system, a systemic study was carried out with ANP-(1-28) in order to confirm or
      to exclude the possible involvement of dopamine in the ANP-induced action in the
      brain. The present study demonstrate that ANP-(1-28) facilitated cage-climbing
      behavior in mice in a dose-dependent manner. When combined with apomorphine, the
      peptide potentiated the effect of the dopamine agonist. The effect of ANP-(1-28)
      in combination with apomorphine could be antagonized by a selected dose of
      haloperidol. These data suggest that ANP might be regarded as a dopamine agonist
      modulating agent and that a dopaminergic mechanism is a possible mode of action
      of ANP in the fear-induced learning studied earlier.

PMID- 1352256
TI  - Haloperidol-induced vacuous chewing in rats: suppression by alpha-methyl
      tyrosine.
AB  - Chronic treatment of rats with haloperidol (1 mg/kg twice daily for 4 weeks)
      induced repetitive vacuous chewing movements (VC), that persisted for over 72 h
      after haloperidol withdrawal. Haloperidol-induced VC were inhibited by the s.c.
      administration of the specific dopamine D1, receptor antagonist, SCH 23390 (0.025
      0.100 mg/kg), in a dose-dependent manner, and were totally suppressed by an acute
      challenge with haloperidol (2 mg/kg i.p.) and by the dopamine synthesis
      inhibitor, alpha-methyl-tyrosine (AMT) (200 mg/kg i.p.). In AMT-treated rats, VC
      were reinstated by the administration of the selective D1 agonist, SKF 38393. The
      results support the hypothesis that chronic haloperidol-induced VC are mediated
      by dopamine acting selectively upon D1 receptors.

PMID- 1352257
TI  - Molecular cloning of the cDNAs coding for the two subunits of soluble guanylyl
      cyclase from human brain.
AB  - Complementary DNA clones corresponding to the 70 and 82 kDa subunits of soluble
      guanylyl cyclase from human adult brain have been isolated and sequenced. Their
      respective open reading frames correspond to 619 amino acids (M(r) 70,469) and
      717 amino acids (M(r) 81,324). Southern blots of human genomic DNA using these
      clones as probes give patterns which might be compatible with the presence of
      more than one copy per gene, or pseudogenes, for each subunit in the human
      genome. Comparison of the protein sequence of the large subunit from adult brain
      with the subunit cloned from human fetal brain (Harteneck, C., Wedel, B.,
      Koesling, D., Malekewitz, J., Bohme, E., and Schultz, G. (1991) FEBS Lett. 292,
      217-222) revealed only 34% homology. This result demonstrates the existence of a
      novel large subunit isoform for soluble guanylyl cyclase in human tissues.

PMID- 1352258
TI  - Melanocyte stimulating hormone activation of tyrosinase in B16 mouse melanoma
      cells. Evidence for a differential induction of two distinct isoenzymes.
AB  - Tyrosinase induction in murine malignant melanocytes by alpha MSH is well known,
      but its molecular basis has not been characterized. Treatment of B16 melanoma
      cells with theophylline or alpha MSH mediates a larger induction of tyrosine
      hydroxylase than of dopa oxidase activity in total cell extracts, and in the
      melanosomal and microsomal fractions. No evidence for the modulation of a
      tyrosinase effector was found. SDS-PAGE and specific activity stain demonstrated
      two forms of tyrosinase, with different degrees of induction by theophylline.
      These results agree with the recent proposal that two tyrosinases, encoded by
      different genes, are present in murine melanocytes.

PMID- 1352259
TI  - Volume-activated Cl- secretion and transepithelial vinblastine secretion mediated
      by P-glycoprotein are not correlated in cultured human T84 intestinal epithelial
      layers.
AB  - The relationship between the P-glycoprotein-mediated vinblastine secretion and
      cell-swelling activated Cl- secretion (conductance) in intact epithelial layers
      of human colonic adenocarcinoma T84 cells has been investigated. Whereas
      vinblastine secretion is effectively inhibited by 100 microM 1,9-dideoxy
      forskolin, volume-stimulated Cl- secretion is unaffected. In contrast, 100 microM
      4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) inhibited the volume
      stimulated Cl- secretion, but was without effect upon transepithelial vinblastine
      secretion. In addition, it was noted that some epithelial layers failed to
      express a volume-stimulated Cl- secretion but maintained a normal level of
      secretory vinblastine flux.

PMID- 1352260
TI  - ATP and GTP as alternative energy sources for vinblastine transport by P-170 in
      KB-V1 plasma membrane vesicles.
AB  - Purified plasma membrane vesicles isolated from multidrug-resistant human KB-V1
      cells accumulate [3H]vinblastine in an energy-dependent manner. The accumulation
      of [3H]vinblastine in the presence of ATP is a saturable process. ATP can be
      replaced by other purine nucleotide triphosphates, of which GTP is the most
      efficient.

PMID- 1352261
TI  - Heat shock proteins of barley mitochondria and chloroplasts. Identification of
      organellar hsp 10 and 12: putative chaperonin 10 homologues.
AB  - Tissue slices from barley seedlings were subjected to heat shock and
      metabolically labelled with [35S]methionine and [35S]cysteine. Mitochondria and
      chloroplasts were isolated and shown to contain two novel heat shock proteins of
      10 and 12 kDa, respectively. The possibility that these proteins, like a
      mitochondrial 10 kDa stress protein recently isolated from rat hepatoma cells
      [(1992) Proc. Natl. Acad. Sci. 89, in press] represent eukaryotic chaperonin 10
      homologues is discussed.

PMID- 1352262
TI  - Identification of the atrial natriuretic factor-R1C receptor subtype (B-clone) in
      cultured rat aortic smooth muscle cells.
AB  - The present report demonstrates the presence in cultured rat aortic smooth muscle
      cells of a natriuretic factor receptor subtype with a specificity typical of the
      ANF-R1C (B-clone) receptor subtype. To prove the existence of this receptor
      subtype in this cell line we show that pCNP-(82-103) is the most potent activator
      of the intrinsic guanylate cyclase activity, and that [125I]pCNP-(82-103) binds
      to a specific receptor subtype which is insensitive to the ANF-R2 specific
      ligand, C-ANF. The investigation of its binding characteristics show the rank
      potency order of the natriuretic factors in competing for pCNP binding to be pCNP
      greater than pBNP greater than rANF. Furthermore it was possible to covalently
      photolabel this receptor subtype with underivatized]125I]pCNP and show that it is
      composed of a single subunit of 130 kDa with very high specificity for pCNP.

PMID- 1352263
TI  - Current concepts in the management of rheumatoid arthritis.

PMID- 1352264
TI  - Purification and characterization of an agglutinin of the soft coral Sinularia
      species.
AB  - A D-galactose-specific agglutinin, named sinularian, has been isolated from the
      soft coral Sinularia sp. by affinity chromatography on acid-treated Sepharose 4B
      and by gel filtration on HPLC. Sinularian was a glycoprotein containing 11%
      sugar. It gave a single band corresponding to 78 kDa in SDS-PAGE, irrespective of
      a treatment with 2-mercaptoethanol. Sinularian agglutinated rabbit erythrocytes
      and murine leukemia cells but not sheep or human ABO erythrocytes. Its
      hemagglutinating activity was Ca(++)-independent. Sinularian promoted binding of
      macrophages to tumor cells.

PMID- 1352265
TI  - Restriction endonuclease analysis of chloroplast DNA from streptomycin-resistant
      mutants of Nicotiana plumbaginifolia.
AB  - Chloroplast DNA isolated from wild-type Nicotiana plumbaginifolia and 12
      maternally inherited streptomycin-resistant mutants was digested with various
      restriction enzymes and the resultant patterns were compared. No gross structural
      alterations of the chloroplast genome were detected in any mutants; however,
      variant patterns owing to the gain or loss of a restriction site were found in
      three mutants, SR1007, SR1019, and SR1022. The variant patterns in SR1019 and
      SR1022 are identical and are the results of mutation in the psbG gene coding for
      a chloroplast membrane protein G, and that in SR1007 is due to mutation in the
      16S rRNA gene. Inheritance of the variant patterns in mutants SR1007 and SR1019
      was studied. The results showed that the variant patterns and streptomycin
      resistance were co-transmitted in reciprocal crosses.

PMID- 1352267
TI  - XXIInd World Congress of the International Association of Logopedics and
      Phoniatrics. Hannover, August 9-14, 1992. Abstracts.

PMID- 1352266
TI  - Angina pectoris and silent ischemia in the elderly: a management update.
AB  - Coronary artery disease accompanied by symptomatic and asymptomatic myocardial
      ischemia is a common entity in older patients. The pathophysiology of myocardial
      ischemia is related to an imbalance in myocardial demand and coronary perfusion.
      Treatment strategies for symptomatic myocardial ischemia include correction of
      aggravating medical conditions (eg, anemia or hypertension) and the use of
      nitrates, beta-adrenergic blockers, salicylates, and calcium-entry blockers,
      alone or in combination. Silent myocardial ischemia is also a prevalent condition
      in older individuals, with and without angina pectoris. Treatment regimens are
      similar to those used in symptomatic patients.

PMID- 1352268
TI  - Natural history of small untreated hepatocellular carcinoma in cirrhosis: a
      multivariate analysis of prognostic factors of tumor growth rate and patient
      survival.
AB  - We analyzed the growth pattern of tumor masses and the survival of 39
      asymptomatic Italian patients with a total of 59 small (less than or equal to 5
      cm in diameter) hepatocellular carcinomas arising from cirrhosis. The total
      length of the observation period ranged from 90 to 962 days, with an average of
      364 +/- 229 (mean +/- S.D.). Doubling time ranged from 27.2 to 605.6 days (mean
      +/- S.D., 204.2 +/- 135; median = 171.6 days). Three different growth patterns
      were recognized: (a) tumors with no or very slow initial growth pattern (doubling
      time greater than 200 days), 10 cases (37%); (b) tumors with declining growth
      rate over time, 9 cases (33.4%); and (c) tumors with almost constant growth rate,
      8 cases (29.6%). Using the stepwise discriminant analysis, we found a score based
      on albumin, alcohol intake, number of nodules, echo pattern and histological type
      that allowed a correct prediction of short doubling time (less than or equal to
      150 days) in 55.6%, medium doubling time (151 to 300 days) in 60% and long
      doubling time (greater than 300 days) in 100% of cases. The estimated survival
      rate of the 39 patients, calculated by the Kaplan-Meier method was 81% at 1 yr,
      55.7% at 2 yr and 21% at 3 yr. Stepwise discriminant analysis showed that a score
      based on sex, HBsAg status, alcohol consumption, ascites, gamma
      glutamyltranspeptidase, prothrombin time, Child-Pugh class and all the
      sonographical parameters could predict 2-yr survival in 100% of cases. We
      conclude that great variability of growth patterns exists among and within small
      hepatocellular carcinomas. Prediction of subsequent growth rate is unreliable in
      most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352269
TI  - Hereditary cystatin C amyloid angiopathy: identification of the disease-causing
      mutation and specific diagnosis by polymerase chain reaction based analysis.
AB  - Hereditary cystatin C amyloid angiopathy (HCCAA) is a dominantly inherited
      disease characterized by amyloidosis, dementia and fatal cerebral hemorrhage of
      young adults. A method for rapid and simple diagnosis of HCCAA is described. It
      is based upon oligonucleotide-directed enzymatic amplification of a 275-bp
      genomic DNA segment containing exon 2 of the cystatin C gene from a blood sample,
      followed by digestion of the amplification product with AluI. Loss of an AluI
      recognition site in the amplified DNA segment from HCCAA patients results in a
      deviating band-pattern at agarose gel electrophoresis, compared with that
      obtained from normal subjects or unaffected HCCAA family members. In a population
      of 9 patients with manifest HCCAA, 14 patients with other causes of brain
      hemorrhage and 16 healthy individuals, the diagnostic procedure displayed a
      sensitivity and specificity for HCCAA of 100%. Amplified DNA segments from 4
      HCCAA patients of four different families were analyzed by nucleotide sequencing;
      the HCCAA-causing mutation in all families was found to be a single T----A
      substitution in the codon for amino acid residue 68 of cystatin C.

PMID- 1352270
TI  - Genetic heterogeneity of early-onset familial breast cancer.
AB  - A gene for early-onset familial breast cancer has recently been mapped to the
      chromosome 17q12-23 region. In order to confirm the gene location, we have tested
      an extensive early-onset breast cancer family with 4 markers in this chromosome
      region. Linkage was negative with all 4 markers. This study suggests that there
      is genetic heterogeneity among early-onset breast cancer families.

PMID- 1352271
TI  - Molecular analysis of the gene for the human vitamin-D-binding protein (group
      specific component): allelic differences of the common genetic GC types.
AB  - DNA sequence analysis of the polymerase chain reaction products, including the
      coding region for amino acids 416 and 420, of the vitamin-D-binding protein (DBP,
      group-specific component, GC) shows allele-specific differences. The GC2 and GC1F
      phenotypes have an aspartic acid residue at amino acid position 416, whereas the
      GC1S phenotype has a glutamic acid at this position. In the GC2 phenotype, amino
      acid 420 is a lysine residue, and in the both common GC1 phenotypes, it is a
      threonine residue. The nucleotide exchanges involve a HaeIII (position 416) and a
      StyI (position 420) restriction site: the HaeIII restriction site is specific for
      the GC*1S allele and the StyI restriction site is specific for the GC*2 allele.
      We have tested 140 individual genomic DNA samples for the HaeIII site and 148
      samples for the StyI site by restriction fragment length polymorphism (RFLP)
      analysis with a DBP-specific direct genomic DNA probe, and have compared these
      findings with the GC phenotype classification, by isoelectric focusing (IEF) of
      the corresponding plasma. The results of the HaeIII RFLP analysis and the IEF
      typing were in complete agreement. By using our DNA probe, we could disclose, in
      addition to the StyI site at amino acid position 420, two further StyI site
      downstream: one was specific for the GC*1S allele and another for the GC*1F
      allele. In 147 samples, there was agreement between the IEF GC typing and the
      analysis of the StyI restriction sites. In a single case, the observed result of
      the StyI-digest differed from the result expected after IEF classification:
      homozygous GC 1F-1F by IEF and heterozygous by StyI RFLP analysis. We discuss
      this finding as a recombination event or a possible silent allele in IEF typing.
      The GC polymorphism revealed by Southern blot analysis of StyI-digests provides
      an informative DNA marker system for chromosome 4q11-q13.

PMID- 1352272
TI  - Reciprocal translocation between the proximal regions of the long arms of
      chromosomes 13 and 15 resulting in unbalanced offspring: characterization by
      fluorescence in situ hybridization and DNA analysis.
AB  - We describe two female siblings with similar clinical features consisting of
      hydrocephalus, scaphocephaly, hypotonia, mongoloid eye slant, blepharophimosis,
      micrognathia, supernumerary mouth frenula and mental retardation. Routine
      cytogenetic studies in the elder patient did not reveal any abnormality, and
      initially it was assumed that the syndrome had an autosomal recessive
      inheritance. However, a slightly larger chromosome 13 was seen in routine G
      banded metaphases of the mother and the youngest of the two siblings. A shorter
      chromosome 15 was detected in the mother only. High resolution banding showed
      that the abnormal chromosome 13 contained an extra G-positive band at 13q12. The
      short chromosome 15 in the mother appeared to have a deletion of band q12.
      Fluorescence in situ hybridization using DNA markers specific to chromosomes 13
      and 15 unequivocally showed that the mother was a carrier of a balanced
      reciprocal translocation t(13;15)(q12;q13), whereas the youngest sibling's
      karyotype was 46,XX,-13,+der(15)t(13;15)(q12;q13)mat, resulting in partial
      monosomy 13pter----q12 and partial trisomy 15pter----q13. The proband is thus
      trisomic for the critical region responsible for Prader-Willi syndrome and
      Angelman syndrome; this was confirmed by DNA analysis demonstrating one paternal
      and two maternal alleles from multiallelic marker loci mapping to 15q11-q13. This
      report illustrates the sensitivity and specificity offered by fluorescence in
      situ hybridization and its usefulness in the diagnosis and delineation of subtle
      chromosomal rearrangements.

PMID- 1352273
TI  - A single base mutation in the gene for type III collagen (COL3A1) converts
      glycine 847 to glutamic acid in a family with Ehlers-Danlos syndrome type IV. An
      unaffected family member is mosaic for the mutation.
AB  - Ehlers-Danlos syndrome type IV, an inherited connective tissue disease, is
      usually caused by mutations in the gene for type III collagen. Here, we describe
      a glycine to glutamic acid substitution in a patient with this syndrome. Previous
      studies had shown that fibroblasts from the patient, his mother and brother
      secreted a reduced amount of type III collagen and also produced an overmodified
      form of the protein that was preferentially retained intracellularly. Peptide
      mapping experiments indicated that the mutation was located within cyanogen
      bromide peptide 9. This was supported by chemical cleavage analysis and
      sequencing of cDNA encoding this region. Allele-specific oligonucleotide
      hybridisation of genomic DNA confirmed that a G to A mutation converted Gly 847
      to Glu. The mutation was present in two other affected family members and also in
      a third, who was clinically unaffected. Further analysis of this unaffected
      individual revealed reduced mutant:normal ratios in DNA obtained from both blood
      and hair samples, showing that she was mosaic for the mutation.

PMID- 1352274
TI  - Structural gene aberrations in mucopolysaccharidosis II (Hunter).
AB  - A total of 14 unrelated German patients with X-linked iduronate-2-sulfatase (IDS)
      deficiency (Hunter syndrome, MPS II) showing variable clinical manifestations was
      screened for structural gene aberrations by Southern analysis. Using the IDS cDNA
      clone c2S15 as a probe, no Southern fragments could be detected in blots in the
      severely affected patient G-65 with respect to DNA digested by HindIII, PstI and
      TaqI, suggesting a total loss of the IDS structural gene. In this patient, the
      flanking loci DXS 297, DXS 296 and DXS 466 were tested. The locus DXS 466 is
      involved in the deletion, whereas both of the other loci are present. A normal
      9.0-kb fragment disappeared and an aberrant fragment of 3.5 kb occurred in the
      HindIII blot of patient G-117. A normal Southern pattern was found in PstI and
      TaqI blots of this patient. This result can be interpreted as the generation of
      an additional HindIII restriction site by point mutation in an IDS gene intron.

PMID- 1352276
TI  - A point mutation changes the polymorphisms pattern in a cystic fibrosis carrier
      family.

PMID- 1352275
TI  - Loss of heterozygosity on chromosome 11 in sporadic gastrinomas.
AB  - Gastrinomas are pancreatic endocrine neoplasms that arise either sporadically or
      are inherited as part of the multiple endocrine neoplasia type I syndrome (MENI).
      Loss of heterozygosity (LOH) in the region flanking the MENI gene at chromosome
      11q13 has been documented in a few sporadic and familial pancreatic endocrine
      tumors, but not previously in sporadic gastrinomas. It has therefore been
      suggested that gastrinomas develop by a mechanism different from other tumors
      associated with the MENI syndrome. We report LOH on chromosome 11 in 5 of 11
      sporadic gastrinomas. Four of these tumors have LOH for markers flanking the MENI
      region. Molecular evaluation of segments of chromosomes 3, 13, and 17 known to
      contain cloned or putative tumor suppressor genes fail to show LOH except at one
      locus in one tumor. These data suggest that a tumor suppressor DNA segment exists
      at 11q13 that may be involved in the development of sporadic gastrinomas.

PMID- 1352277
TI  - XIV World Conference on Health Education. Helsinki, Finland, June 16-21, 1991.

PMID- 1352278
TI  - Associated soft tissue injury of fracture of the body of talus.

PMID- 1352279
TI  - An introduction to the possible role of central nervous system structures in
      neuroendocrine-immune systems interaction.
AB  - The involvement of different regions of the brain in the immune response was
      investigated with the aid of small electrolytic lesions. The lesions were placed
      in such a way that they covered different areas of the brain stem, basal ganglia,
      but also some parts of the frontal cortex. The cellular immune response as well
      as DNA synthesis with the aid of labelled precursors was measured. The results
      suggest the possibility of the existence of three circuits. One circuit
      represents catecholaminergic cell group A1-7 in reticular formation, nucleus
      parabrachialis and central ncl. amygdalae. The second circuit represents
      serotonergic rapheal groups B6.8, hypothalamus and ncl. basomedialis of amygdala.
      The third circuit represents ncl. amygdalae and the medial part of frontal
      cortex, namely the cingulate cortex area 1-2. The close correlation between the
      changes of the immune response and the CNS activity was also investigated in the
      experiments with immunosuppressed and immunostimulated animals by measuring of
      the turnover of some neurotransmitters but also by recording
      electrocephalographic activity.

PMID- 1352280
TI  - Papers from the 5th International Conference on Immunopharmacology. Tampa,
      Florida, 26-30 May 1991.

PMID- 1352282
TI  - Erratum and comments re: Critical bandwidth and consonance: their operational
      definitions in relation to cochlear nonlinearity and combination tones (Hear.
      Res. 54, 209-246, 1991).

PMID- 1352283
TI  - Biological control of mosquitoes and other biting flies by Bacillus sphaericus
      and Bacillus thuringiensis.

PMID- 1352281
TI  - Mouse-human chimeric antibody MH171 against the multidrug transporter P
      glycoprotein.
AB  - We have developed a mouse-human chimeric antibody MH171, in which the antigen
      recognizing variable regions of the mouse monoclonal antibody MRK17 are joined
      with the constant regions of human IgG1 antibodies. The MRK17 recognizes
      specifically the multidrug transporter P-glycoprotein and inhibits the growth of
      human multidrug resistant (MDR) tumor cells in vitro and in the xenograft nude
      mouse model system. The established chimeric MH171 antibody forms an apparently
      intact IgG composed of heavy and light chains covalently assembled via disulfide
      bonds in sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis and
      is specific to MDR cell lines with a similar affinity to the original mouse
      MRK17. MH171 also displays strong antibody-dependent cell-mediated cytotoxicity
      to the target cells in vitro, when human mononuclear cells are used as effector
      cells. The chimeric antibody against P-glycoprotein, MH171, should be a useful
      agent in the treatment of human drug-resistant tumors.

PMID- 1352284
TI  - [Pancreaticopleural fistula].
AB  - We describe the case of a patient with a subdiaphragmatic collection and massive
      pleural effusion due to a pancreatico-pleural fistula. The fistulous tract was
      secondary to the extension of an intraabdominal pseudocyst through the
      diaphragmatic hiatus into the mediastinum, where it perforated into the right
      pleural cavity. Spontaneous closure of the fistula occurred after a three-week
      treatment with somatostatin.

PMID- 1352286
TI  - Substitution of the insulin receptor transmembrane domain with the c-neu/erbB2
      transmembrane domain constitutively activates the insulin receptor kinase in
      vitro.
AB  - To examine the role of the transmembrane domain (TM) of the insulin receptor in
      insulin-induced receptor kinase activation, we prepared four mutated insulin
      receptors: 1) a Val938----Asp substitution (IR/TMv----D), 2) insertion of a 3
      amino acid repeat (Val938-Phe939-Leu940) (IR/TM+3), or the entire TM was replaced
      by the corresponding domain of either the 3) platelet-derived growth factor
      (PDGF) receptor (IR/TMPDGFR) or 4) c-neu/erbB2 proto-oncogene product (IR/TMc
      neu). Each mutant receptor was stably expressed in Chinese hamster ovary cells,
      assessed by fluorescence-activated cell sorting, insulin binding, and
      biosynthetic labeling. All mutant receptors exhibited normal affinity for
      insulin. Pulse-chase experiments showed that each proreceptor was processed into
      alpha- and beta-subunits, although the rate of IR/TMV----D conversion was reduced
      approximately 3-fold. With IR/TMPDGFR, IR/TMV----D, and IR/TM+3 basal and insulin
      stimulated levels of autophosphorylation and tyrosine kinase activation were
      normal, both in wheat germ agglutinin (WGA)-purified receptor preparations and
      intact cells. By contrast, following WGA purification or isolation of crude
      membranes, IR/TMc-neu was a constitutively active autokinase and substrate kinase
      in vitro. However, in intact cells insulin-stimulated autophosphorylation and
      kinase activity appeared normal. We conclude that although there is considerable
      latitude in acceptable structure, residues within the insulin receptor
      transmembrane domain can play a functional role in regulation of insulin receptor
      tyrosine kinase activity.

PMID- 1352285
TI  - Chaperonins groEL and groES promote assembly of heterotetramers (alpha 2 beta 2)
      of mammalian mitochondrial branched-chain alpha-keto acid decarboxylase in
      Escherichia coli.
AB  - We have investigated the possible role of chaperonins groEL and groES in the
      folding and assembly of heterotetramers (alpha 2 beta 2) of mammalian
      mitochondrial branched-chain alpha-keto acid decarboxylase (E1) in Escherichia
      coli. The mature E1 alpha subunit fused to maltose-binding protein (MBP) was
      coexpressed with mature E1 beta on the same vector in ES- and EL- mutant strains.
      Only small or trace amounts of active E1 component were obtained.
      Cotransformation of the ES- mutant host with a second vector overexpressing groEL
      and groES resulted in a greater than 500-fold increase in E1-specific activity.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the content
      of both MBP-E1 alpha and E1 beta polypeptides was markedly increased in the
      presence of overexpressed chaperonin proteins. The time course studies showed
      that the increase in E1-specific activity and subunit levels correlated with the
      increase in groEL and groES until the concentration of the chaperonins reached a
      saturating level in the cell. The functional MBP-E1 fusion protein from ES-
      double transformants were purified by amylose resin affinity chromatography. The
      MBP moiety was removed by subsequent digestion with Factor Xa endoprotease,
      followed by Sephacryl S-300HR chromatography. It was found that E1 alpha and E1
      beta assembled into an active 160-kDa species, which was consistent with the
      alpha 2 beta 2 structure of E1. The present results demonstrate that chaperonins
      groEL and groES promote folding and assembly of heterotetrameric proteins of
      mammalian mitochondrial origin.

PMID- 1352287
TI  - Complete amino acid sequence of the human alpha 5 (IV) collagen chain and
      identification of a single-base mutation in exon 23 converting glycine 521 in the
      collagenous domain to cysteine in an Alport syndrome patient.
AB  - We have generated and characterized cDNA clones providing the complete amino acid
      sequence of the human type IV collagen chain whose gene has been shown to be
      mutated in X chromosome-linked Alport syndrome. The entire translation product
      has 1,685 amino acid residues. There is a 26-residue signal peptide, a 1,430
      residue collagenous domain starting with a 14-residue noncollagenous sequence,
      and a Gly-Xaa-Yaa-repeat sequence interrupted at 22 locations, and a 229-residue
      carboxyl-terminal noncollagenous domain. The calculated molecular weight of the
      mature alpha 5(IV) chain is 158,303. Analysis of genomic DNA from members of a
      kindred with Alport syndrome revealed a new HindIII cleavage site within the
      coding sequence of one of the cDNA clones characterized. The proband had a new
      1.25-kilobase HindIII fragment and a lack of a 1.35-kilobase fragment, and his
      mildly affected female cousin had both alleles. The mutation which was located to
      exon 23 was sequenced from a polymerase chain reaction-amplified product, and
      shown to be a G----T change in the coding strand. The mutation changed the GGT
      codon of glycine 521 to cysteine. The same mutation was found in one allele of
      the female cousin. The results were confirmed by allele-specific hybridization
      analyses.

PMID- 1352288
TI  - Selective inhibitors of GTP synthesis impede exocytotic insulin release from
      intact rat islets.
AB  - To investigate whether GTP concentrations can be a regulatory step in exocytotic
      hormone secretion, we treated isolated rat islets with mycophenolic acid (MPA) or
      mizoribine, two selective inhibitors of de novo GTP synthesis. When islets were
      cultured overnight in purine-free medium containing the drug, MPA reduced GTP
      levels by up to 81 +/- 1%; guanine circumvented this block via the nucleotide
      "salvage" pathway. MPA concomitantly inhibited glucose (16.7 mM)-induced insulin
      secretion in batch-type incubations (or perifusions), by up to 68% at 50
      micrograms/ml. Although the inhibition of secretion occurred over a similar
      concentration range as the reduction in total GTP content, the two variables were
      not directly correlated. However, the secretory effects also were prevented by
      adding guanine, but not hypoxanthine or xanthine, to the culture medium. Similar
      results for GTP content and insulin release were seen using mizoribine. Insulin
      content was modestly (-18%) reduced by MPA but indices of fractional release
      (release/insulin content) were also markedly impaired. Although MPA also reduced
      ATP levels more modestly (-39%) and increased UTP (+87%), these were not the
      cause of the secretory defect since adenine restored ATP and UTP nearly to
      normal, but did not alter the reduction in GTP content or insulin secretion. MPA
      also inhibited secretion induced by amino acid or by a phorbol ester but had
      virtually no effect on release induced by a depolarizing concentration of K+,
      suggesting that GTP depletion does not merely impede Ca+ influx or directly block
      Ca(2+)-activated exocytosis. However, a severe reduction of GTP content did not
      prevent the pertussis toxin-sensitive inhibition of insulin release induced by
      epinephrine, suggesting that the function of heterotrimeric GTP-binding proteins
      is not limited by ambient GTP concentrations. Although these studies do not
      elucidate the exact site(s) in the exocytotic cascade which depend on intact GTP
      stores, they do provide the first direct evidence that GTP is required (and can
      be rate limiting) for insulin release.

PMID- 1352289
TI  - Site-directed mutagenesis of serine 40 of rat tyrosine hydroxylase. Effects of
      dopamine and cAMP-dependent phosphorylation on enzyme activity.
AB  - Rat tyrosine hydroxylase expressed with a baculovirus expression system contains
      covalent phosphate and has kinetic parameters consistent with those expected of
      phosphorylated enzyme (Fitzpatrick, P. F., Chlumsky, L. J., Daubner, S. C., and
      O'Malley, K. L. (1990) J. Biol. Chem. 265, 2042-2047). The phosphorylation site
      was identified as serine 40, by purifying the enzyme from cells grown in the
      presence of [32P]phosphate. Replacement of serine 40 with alanine by site
      directed mutagenesis prevented phosphorylation but had little effect on the
      steady-state kinetic parameters at pH 7. Both wild type and S40A tyrosine
      hydroxylase were expressed in Escherichia coli; the kinetic parameters of the
      enzymes purified from bacteria were nearly identical to those of the enzymes
      expressed with the baculovirus system, although the bacterially expressed enzyme
      contained no covalent phosphate. Treatment of this wild type enzyme with cAMP
      dependent protein kinase decreased the KBH4 value about 2-fold but had no effect
      on the Vmax value at pH 7. Treatment with a stoichiometric amount of dopamine
      decreased the Vmax value 15-fold and increased the KBH4 value 2-3-fold.
      Phosphorylation of the dopamine-bound enzyme increased the Vmax value 10-fold and
      decreased the KBH4 value 2-fold. The kinetic parameters of the dopamine-bound
      recombinant enzyme were identical to those of enzyme purified from PC12 cells. In
      contrast, the S40A enzyme was converted to a less active form by treatment with
      dopamine but was not affected by phosphorylating conditions. These results are
      consistent with a model in which the major effect of phosphorylation of serine 40
      is to relieve tyrosine hydroxylase from the inhibitory effects of catecholamines.

PMID- 1352290
TI  - Molecular cloning of rat prostate transglutaminase complementary DNA. The major
      androgen-regulated protein DP1 of rat dorsal prostate and coagulating gland.
AB  - Complementary DNA (cDNA) that codes for a major androgen-dependent secretory
      protein of rat coagulating gland and dorsal prostate, dorsal protein 1 (DP1), was
      isolated by molecular cloning. Recombinant DP1 cDNA clones were identified from a
      bacteriophage lambda gt11 rat coagulating gland expression library using an
      affinity purified polyclonal antibody. Amino acid sequence deduced from DNA
      contained sequences identical with several DP1 cyanogen bromide cleavage
      fragments. Northern blot hybridization of poly(A) RNA isolated from intact rat
      dorsal prostate and coagulating gland revealed a predominant messenger RNA (mRNA)
      species of approximately 3200 nucleotides. Tissue-specific expression of DP1 mRNA
      was indicated by the absence of DP1 mRNA in ventral prostate and other tissues of
      the rat. Expression of DP1 mRNA was androgen-dependent, decreasing approximately
      80% 7 days after castration and increasing rapidly following androgen
      replacement. Southern blot analysis of restriction enzyme-digested rat DNA
      indicated that DP1 is encoded by a single gene and that no major genomic
      rearrangements accounted for its lack of expression in the dorsal prostate
      derived rat Dunning tumor. Sequence comparisons revealed that rat prostate DP1
      shares sequence identity with Factor XIIIa and tissue transglutaminase, including
      the active center, GQCWVF, indicating that DP1 is a member of the
      transglutaminase gene family.

PMID- 1352291
TI  - Somatostatin gene transcription regulated by a bipartite pancreatic islet D-cell
      specific enhancer coupled synergetically to a cAMP response element.
AB  - The insulin-, glucagon-, and somatostatin-producing cells in the pancreatic
      islets derive from a common precursor stem cell and differentiate sequentially
      during embryonic development, thereby providing an informative model for the
      study of the transcriptional mechanisms involved in the control of cell-specific
      gene expression. Relative to the early expression of the glucagon and insulin
      genes on embryonic days 10 and 12, respectively, the expression of the
      somatostatin gene is delayed (day 17). The relatively late expression of the
      somatostatin gene indicates the involvement of both negative and positive
      transcriptional control mechanisms. We show that the expression of the
      somatostatin gene in pancreatic islet cells is accomplished by the interplay of
      both positive and negative cis-regulatory DNA elements. We have characterized the
      functional properties of one of these positive control elements, the somatostatin
      gene upstream enhancer element (SMS-UE). The SMS-UE is a pancreatic islet D-cell
      specific transcriptional regulator that acts synergistically with the cyclic AMP
      response element. Mutation-expression and cell-free transcription analyses show
      that the SMS-UE is a bipartite element with two interdependent functional
      domains. Our results indicate that the SMS-UE is part of a functional unit that
      includes other transcriptional control elements of the somatostatin gene proximal
      promoter, and that they act together to regulate the D-cell-specific
      transcription of the somatostatin gene in the islet cells of the pancreas.

PMID- 1352293
TI  - In vitro mutagenesis of potential N-glycosylation sites of arylsulfatase A.
      Effects on glycosylation, phosphorylation, and intracellular sorting.
AB  - The correct intracellular sorting of lysosomal enzymes such as arylsulfatase A
      depends on the presence of mannose 6-phosphate residues on high mannose type
      oligosaccharides. The arylsulfatase A cDNA contains three potential N
      glycosylation sites, two of which are utilized. We have mutated one or two of the
      N-glycosylation sites and analyzed the glycosylation, phosphorylation, and
      intracellular sorting of the mutant arylsulfatase A polypeptides. The results
      show that each of the three glycosylation sites (I, II, and III) can be
      glycosylated, but glycosylation at sites I and II is mutually exclusive. In
      mutants with one oligosaccharide side chain at positions I, II, or III all side
      chains can acquire mannose 6-phosphate residues irrespective of their location.
      This demonstrates spatial flexibility of the phosphotransferase, which
      specifically recognizes lysosomal enzymes and initiates the addition of mannose 6
      phosphate residues on oligosaccharide side chains. However, these mutants have
      different intracellular sorting efficiencies and seem to use different (mannose 6
      phosphate receptor-dependent and -independent) sorting pathways.

PMID- 1352292
TI  - Somatostatin gene upstream enhancer element activated by a protein complex
      consisting of CREB, Isl-1-like, and alpha-CBF-like transcription factors.
AB  - The expression of the genes encoding the hormones glucagon, insulin,
      somatostatin, and pancreatic polypeptide in the endocrine islets of the pancreas
      is regulated in a cell-specific manner, defining four distinct cellular
      phenotypes (A-, B-, D-, and F-cells, respectively). Binding of nuclear proteins
      to cognate DNA sequences within cis-acting regulatory elements mediates the
      transcriptional events that result in the cell-specific activation or repression
      of gene expression. In a parallel study, we describe the functional properties of
      the SMS-UE, a pancreatic islet D-cell specific enhancer element that regulates
      the expression of the somatostatin gene and contains two interdependent domains,
      A and B. In the studies described herein, we have characterized the nuclear
      proteins that recognize the SMS-UE. Domain A of the SMS-UE is a DNA enhancer
      sequence that is identical to that bound by the ubiquitously distributed CCAAT
      box-binding protein alpha-CBF, a transcription factor that regulates the
      expression of the human chorionic gonadotrophin alpha-subunit gene. The B-domain,
      on the other hand, binds an islet cell-specific protein with characteristics
      similar to those of Isl-1, a transcriptional activator protein that binds to the
      E2 enhancer of the rat insulin-1 gene. In addition, the SMS-UE binds
      transcription factor CREB but not CREM, the close homolog of CREB, on a site
      adjacent to, or overlapping, the 3' end of domain B. We show that the carboxyl
      terminal bZIP domain of CREB binds to the cAMP response element of the
      somatostatin gene but is not sufficient for binding to the SMS-UE, and we present
      evidence suggesting that CREB.SMS-UE binding requires stabilization by a region
      of the protein located within the transactivation domain.

PMID- 1352294
TI  - Tetanus toxin potently stimulates tissue transglutaminase. A possible mechanism
      of neurotoxicity.
AB  - The observation that tetanus toxin (TT) contains two sequences that show homology
      to known transglutaminase (TGase) substrate sites suggested that the toxin and
      TGase might interact. This prediction was confirmed by two pieces of evidence.
      First, TT potently stimulated the enzymatic activity of TGase. The effect was
      maximal at physiological (micromolar) concentrations of the endogenous TGase
      regulators calcium and GTP. Second, TT and TGase displayed marked variations of
      their intrinsic fluorescence properties when they were coincubated, indicating
      the occurrence of binding between them. TT-TGase binding and TGase activation
      occurred at similar concentrations of TT and are probably causally related. The
      activation of TGase, an enzyme present in nerve endings that, when activated, can
      irreversibly cross-link cellular proteins, might mediate the neurotoxic action of
      TT.

PMID- 1352295
TI  - Photoaffinity labeling of the organic cation/H+ exchanger in renal brush border
      membrane vesicles.
AB  - The brush border membrane of the proximal tubule contains two efflux pathways for
      organic cations from the cell to the tubular fluid: a P-glycoprotein and an
      organic cation/H+ exchanger. There is evidence that they transport many of the
      same substrates. Their structural relatedness is unknown and is the subject of
      this report. The experimental approach was to identify the exchanger with
      photoaffinity labeling reagents. The rationale was that if the P-glycoprotein and
      the organic cation/H+ exchanger transport many of the same substrates, then they
      might be photoaffinity labeled by the same reagents. [125I]Iodoarylazidoprazosin
      and [3H]azidopine are two reagents, which have been used, to photoaffinity label
      the P-glycoprotein. We found that several polypeptides were photolabeled in a
      time- and concentration-dependent manner. The photoincorporation into only two of
      these polypeptides (41 and 28 kDa) was blocked extensively by the presence of
      known substrates for the exchanger. The photoaffinity labeling of only the 41-kDa
      polypeptide was affected by treatment with the chemical reagents, N
      ethylmaleimide and dithiothreitol, which are known to affect the exchanger
      reaction. The findings are consistent with the interpretation that a 41-kDa
      polypeptide is, or is a component of, the exchanger.

PMID- 1352296
TI  - Heterozygosity for apolipoprotein E-4Philadelphia(Glu13----Lys, Arg145----Cys) is
      associated with incomplete dominance of type III hyperlipoproteinemia.
AB  - Apolipoprotein (apo) E-4Philadelphia is a double mutant of apoE in which residue
      13 of the mature protein, glutamic acid (GAG), is replaced by lysine (AAG) and
      amino acid 145, arginine (CGT), is converted to cysteine (TGT). These mutations
      result in two restriction fragment length polymorphisms for the enzymes AvaI and
      BbvI, a smaller apparent molecular weight of apoE-4Philadelphia on sodium dodecyl
      polyacrylamide gels, and severe type III hyperlipoproteinemia (HLP) in a 24-year
      old homozygous female (Lohse, P., Mann, W. A., Stein, E. A., and Brewer, H. B.,
      Jr. (1991) J. Biol. Chem. 266, 10479-10484). In the current study, we have
      extended our analysis to include nine additional family members of the
      Philadelphia kindred spanning four generations. DNA and protein analysis
      demonstrated that the originally described propositus is a true homozygote for
      the epsilon-4Philadelphia allele and that six of the nine family members are
      heterozygous for the mutated allele and the normal epsilon-3 allele or, in one
      case, the epsilon-4 allele. Heterozygosity for apoE-4Philadelphia leads to the
      expression of a moderate form of type III HLP without clinical manifestations.
      These results are consistent with a dominant mode of inheritance of this
      dyslipoproteinemia. The simultaneous presence of unaffected individuals,
      heterozygotes, and a homozygote in the Philadelphia kindred makes it possible for
      the first time to demonstrate that the mutant apoE exhibits an incomplete or
      partial dominance of type III HLP. Heterozygosity for the normal epsilon-3 allele
      appears to have an influence on the expression of type III HLP, resulting in a
      phenotype intermediate between that of the two homozygous states.

PMID- 1352297
TI  - International Society for the Study of Custom Prostheses. San Francisco, USA,
      October 17-19, 1991. Abstracts.

PMID- 1352298
TI  - Alterations of the c-erbB2 gene in human breast cancer.
AB  - DNA amplification, RNA overexpression and p185 protein expression of the c-erbB2
      oncogene were investigated in 109 cases of breast cancer with the aim of
      evaluating any correlation between the different methods. A correlation between
      Southern blotting and immunohistochemical analysis of paraffin-embedded material
      was found. Thus, amplification of the c-erbB2 oncogene leads to overexpression of
      the p185 protein. By contrast, no statistical correlation could be shown between
      RNA overexpression, measured by Northern blotting, and immunohistochemical p185
      membrane stainings. It is of special interest that most of the cases that are
      positive for Northern blotting and negative for immunochemistry are negative for
      Southern blotting as well. Contradictory findings between RNA overexpression and
      lack of immunohistochemical staining of p185 give rise to the assumption that a
      defective protein is encoded, which cannot be incorporated into the substructures
      of the tumour cell membrane. When screening for point mutations in the
      transmembrane domain of the c-erbB2 oncogene, no point mutation could be
      detected, either by using the endonuclease FokI, which cuts at position 2012 (the
      point mutation in the neu gene of the rat), or by direct sequencing.

PMID- 1352299
TI  - Expression of Her2/neu oncogene product p185 in correlation to
      clinicopathological and prognostic factors of gastric carcinoma.
AB  - The expression of the Her2/neu gene product p185 was retrospectively analyzed in
      58 patients with gastric carcinoma. The results were correlated to various
      clinicopathological and prognostic factors. Positive membrane staining for p185
      could be detected in 38% of the patients (22/58). Membrane staining was
      significantly greater in well and moderately differentiated tumors of the
      intestinal type when compared with poorly differentiated lesions and carcinomas
      of the diffuse type (P less than 0.01). Positive membrane staining did not
      correlate with site and tumor stage, but T1 lesions had less membrane staining
      than more advanced primary tumors. Overall survival showed no difference between
      p185-positive and negative cases. Multivariate analysis defined a subgroup of
      curatively resected patients with stage III and IV disease that had a
      statistically significant poorer survival when p185 was overexpressed (P =
      0.005). Overexpression of the Her2/neu product p185 appears to be associated with
      intestinal-type gastric carcinoma and may help in identifying a subset of
      patients at increased risk for shorter survival.

PMID- 1352300
TI  - Selective inhibition of protein targeting to the apical domain of MDCK cells by
      brefeldin A.
AB  - Dipeptidyl peptidase IV (DPPIV) is mainly vectorially targeted to the apical
      surface in MDCK cells. BFA was found to abolish the apical targeting of DPPIV.
      This BFA effect could be achieved under conditions where the ER to Golgi
      transport and the total surface expression of DPPIV were essentially unaffected.
      BFA executed its effect during the transport from the trans-Golgi network (TGN)
      to the surface. The inhibition of apical targeting resulted in enhanced mis
      targeting to the basolateral surface. The mistargeted DPPIV was transcytosed back
      to the apical domain only after BFA withdrawal. In contrast, the basolateral
      targeting of uvomorulin was unaffected by BFA. These results established that the
      apical targeting of DPPIV was selectively abolished by BFA.

PMID- 1352301
TI  - A cryptopromoter is activated in the proliferating cell nuclear antigen gene of
      growth arrested cells.
AB  - We have examined the regulation of the proliferating cell nuclear antigen gene
      (PCNA) in a hamster fibroblast cell line (tk-ts13) which is temperature sensitive
      for growth. These tk-ts13 cells, at the restrictive temperature, are growth
      arrested in the G1 phase of the cell cycle. The cells were stably transfected
      with a full length human PCNA gene, and the resulting cell lines (K525 cells)
      were analyzed. We find that, in growth arrested K525 cells, a cryptopromoter is
      activated in the transfected human PCNA gene. The cryptopromoter resides in
      intron 4 which is necessary for proper regulation of the PCNA gene. Removal of
      this intron leads to increased expression of PCNA in cells which have entered the
      G0 state. An Alu sequence residing in intron 4 is implicated as the promoter
      element which is active during growth arrest.

PMID- 1352302
TI  - Reduced mRNA levels for the multidrug-resistance genes in cAMP-dependent protein
      kinase mutant cell lines.
AB  - We have previously shown that in Chinese hamster ovary (CHO) cells, a mutant cell
      line with a defective regulatory subunit (RI) for the cAMP-dependent protein
      kinase (Abraham et al: Mol. Cell. Biol., 7:3098-3106, 1987), and a transfectant
      cell line expressing the same mutant kinase, showed increased sensitivity to a
      number of drugs that are known to be substrates for the multidrug transporter (P
      glycoprotein). In the current study we have investigated the mechanism by which
      cAMP-dependent protein kinase controls drug resistance. We report here that the
      sensitivity of the kinase defective CHO cell lines to multiple drugs results from
      decreased RNA levels for the multidrug-resistance gene. Similar results were
      obtained with mouse Y1 adrenal cells. Wild-type Y1 cells had high levels of P
      glycoprotein due to expression of both the mdr1b and mdr2 genes, whereas the cAMP
      dependent protein kinase mutant Kin 8 cells had decreased RNA levels for these
      genes. A Kin 8 transfectant with restored cAMP-dependent protein kinase activity
      recovered mdr expression, indicating a cause and effect relationship between the
      protein kinase mutations and mdr expression. No changes in nuclear run-off assays
      could be detected, suggesting a non-transcriptional mechanism of regulation. Wild
      type Y1 cells are more drug sensitive despite having higher levels of P
      glycoprotein than the mutant cells. This paradoxical result may be explained by
      the higher rate of synthesis of steroids by the wild-type Y1 cells, which appear
      to be inhibitors of P-glycoprotein transport activity.

PMID- 1352303
TI  - Ubiquinone protects cultured neurons against spontaneous and excitotoxin-induced
      degeneration.
AB  - Ubiquinone is an endogenous quinone with pharmacological actions mainly related
      to its antioxidant properties. Here we report that ubiquinone protects cultured
      cerebellar granule cells against glutamate-induced neurotoxicity. In control
      cultures at 9 days of maturation in vitro (DIV), a 30-min exposure to 100 microM
      glutamate induced neuronal degeneration, as reflected by the great percentage
      (greater than 90%) of cells labeled with propidium iodide 24 h after the
      exposure. Glutamate-induced neuronal death was dramatically reduced in cultures
      treated daily with ubiquinone since the second DIV. In these cultures, glutamate
      failed to induce a "delayed" increase in the influx of 45Ca2+, an established
      parameter of excitotoxicity. Similarly, repeated addition of ubiquinone
      attenuated in a concentration-dependent manner the age-dependent degeneration of
      granule cells that is due to the toxic action of the endogenous glutamate
      progressively released into the medium. These results suggest that ubiquinone may
      be a useful drug in the therapy of acute and chronic neurodegenerative diseases
      related to hyperactivity of excitatory amino acid neurotransmission.

PMID- 1352304
TI  - Adenosine receptor blockade augments interstitial fluid levels of excitatory
      amino acids during cerebral ischemia.
AB  - The excitotoxic hypothesis suggests that cerebral ischemic damage results in part
      from the accumulation of the excitatory and potentially toxic neurotransmitters
      glutamate and aspartate. Adenosine, which also increases during cerebral
      ischemia, is proposed to inhibit neurotransmitter release. The purpose of this
      study was to determine if adenosine receptor blockade exacerbates the
      accumulation of glutamate and aspartate during cerebral ischemia. Microdialysis
      probes, implanted bilaterally in the caudate nucleus of halothane-anesthetized
      rats, were used to (1) assess changes in interstitial fluid (ISF) glutamate,
      aspartate, adenosine, and adenosine metabolites; (2) measure local cerebral blood
      flow (H2 clearance); and (3) deliver 8-(p-sulfophenyl)theophylline (SPT), an
      adenosine receptor antagonist, locally to the brain. The probe on one side of the
      brain was perfused with artificial cerebrospinal fluid (CSF) containing 10(-3) M
      SPT, while the probe on the opposite side received only artificial CSF. Animals
      were exposed to 20 min of ischemia (carotid occlusion+arterial blood pressure =
      50 mm Hg) followed by 60 min of reperfusion. Dialysate glutamate and aspartate
      increased during and after cerebral ischemia, but were increased to a greater
      extent in the presence of adenosine receptor blockade. Likewise, the increase in
      dialysate adenosine and adenosine metabolites was enhanced on the side of locally
      administered SPT. These data suggest that endogenous adenosine attenuates the
      accumulation of glutamate and aspartate during cerebral ischemia.

PMID- 1352305
TI  - 11th International Symposium on High Performance Liquid Chromatography of
      Proteins, Peptides and Polynucleotides. Washington, DC, October 20-23, 1991.

PMID- 1352306
TI  - Measurement of amino acid compositions of glycoprotein systems by gas-phase
      hydrolysis and reversed-phase high-performance liquid chromatography.
AB  - Interest in glycoproteins and their compositions has increased in recent years.
      Work described in this report illustrates the use of an amino acid analysis
      protocol involving gas-phase hydrolysis and reversed-phase high-performance
      liquid chromatography of glycoprotein systems at microgram levels. In other amino
      acid analysis protocols the problem of losses of amino acids of glycoproteins has
      been documented. These losses were due to various reactions, referred to as
      browning or Maillard reactions, which yielded a residue from which amino acids
      were not recoverable. In our work, three glycoprotein systems are examined:
      ovalbumin, sICAM-1, and bovine serum albumin--which is naturally unglycosylated,
      but is spiked with about 30% saccharides. In all three cases, the compositional
      agreement between the molar ratio of amino acids determined empirically and that
      predicted is greater than 90%. Thus it is shown that the adverse effects of
      Maillard-type reactions are avoided, and the presence of carbohydrates causes
      negligible interferences with amino acid analysis performed under the conditions
      described herein.

PMID- 1352308
TI  - Hormone secretion in vitro by plurihormonal pituitary adenomas of the acidophil
      cell line.
AB  - Pituitary tumors producing GH and PRL are morphologically classified as
      monomorphous bihormonal acidophil stem cell adenomas (ASCAs) which cause
      hyperprolactinemia and two tumor types which are usually associated with
      acromegaly, the monomorphous plurihormonal mammosomatotroph adenomas (MSAs) and
      bimorphous mixed somatotroph-lactotroph adenomas. We studied 12 MSAs, 2 ASCAs,
      and 10 mixed adenomas in vitro to assess the secretory behavior of these tumors
      diagnosed by immunohistochemistry and electron microscopy. GH release by MSAs and
      all but one mixed tumor was greater than that of PRL; the opposite was true of
      the ASCAs. One mixed tumor which caused impotence and hyperprolactinemia
      contained predominantly lactotrophs and released greater amounts of PRL than of
      GH in vitro. All 12 MSAs and 6 of 10 mixed tumors released alpha-subunit of
      glycoprotein hormones. Incubation with GHRH increased release of GH and PRL by
      all tumors and of alpha-subunit when present; the responses of all hormones were
      parallel among MSAs whereas among mixed adenomas, GH and alpha-subunit had
      greater responses than PRL. TRH stimulated GH, PRL, and alpha-subunit release by
      MSAs in parallel; among mixed adenomas, PRL response was generally greater than
      that of GH or alpha-subunit. SRIH markedly reduced GH release by all MSAs; it
      inhibited GH and alpha-subunit release by mixed tumors more than it affected PRL.
      Bromocriptine inhibited GH, PRL, and alpha-subunit release by most MSAs and mixed
      tumors but did not inhibit GH or PRL release by ASCAs. This study demonstrates
      release of GH, PRL, and alpha-subunit by these morphologically classified
      plurihormonal tumors in vitro. Variable quantities of GH and PRL released by the
      different tumor types correlate with immunohistochemical and clinical data. The
      dynamic studies indicate that regulation of GH, PRL, and alpha-subunit release
      can be affected by GHRH, TRH, SRIH, and bromocriptine in these adenomas and
      suggest differences in receptor status. Our data strengthen the view that these
      three plurihormonal adenomas of the acidophil cell line are not only
      morphologically but also functionally different and warrant separation.

PMID- 1352307
TI  - Multilocus mapping of the X-linked hypophosphatemic rickets gene.
AB  - X-linked hypophosphatemic rickets (HYP), the most common form of familial
      hypophosphatemic (vitamin D-resistant) rickets, is an X-linked dominant disorder
      characterized by decreased renal tubular phosphate reabsorption and consequent
      hypophosphatemia. Despite the application of a wide variety of biochemical and
      cell biology techniques, controversy exists regarding whether a primary renal
      abnormality underlies the abnormal phosphate transport or if this defect is
      secondary to the effects of a hormonal/metabolic factor. Thus localization of the
      HYP gene and its ultimate cloning may be necessary to elucidate the
      pathophysiology of the disorder. In order to map the human HYP gene we
      investigated several new polymorphic probes for linkage to HYP and constructed a
      map of markers around the gene. The database used to ascertain linkage and
      perform mapping included 5 large HYP kindreds, 40 Centre d'Etudie Polymorphisms
      Humain reference pedigrees, and 19 kindreds which had been obtained for other
      disease linkage studies. Two point LOD scores (odds of linkage, log10) indicate
      that the probes DXS365, DXS257, DXS451, and DXS41 are tightly linked to the HYP
      locus. Indeed, there were no cross-overs between DXS365 and HYP with a peak LOD
      score of 13.98 [recombination fraction (theta) = 0.00]. Moreover, multipoint
      analysis reveals a probable locus order of: Xtel-DXS315-DXS43-DXS257-HYP-DXS41
      DXS4 51-Xcen. The likelihood of HYP occurring between DXS257 and DXS41 is 407:1
      over the next most likely position. DXS365 is located between DXS41 and DXS43 but
      could not be located with respect to HYP and DXS257. Regardless, we have located
      the HYP gene between the flanking markers DXS257 (telomeric) and DXS41
      (centromeric) which are 3.5 centiMorgans apart. Thus, the results of this study
      will facilitate attempts to further localize and eventually clone the gene.

PMID- 1352309
TI  - Clinical and genetic features of adrenocortical lesions in multiple endocrine
      neoplasia type 1.
AB  - In multiple endocrine neoplasia type 1 (MEN-1), benign enlargement of the adrenal
      cortex has been found in about one third of necropsy cases. To elucidate the
      clinical and genetic characteristics of the MEN-1 adrenal lesion, we have
      investigated 33 MEN-1 patients. Twelve individuals (37%) demonstrated adrenal
      enlargement, which was bilateral in 7 of them. Histopathology revealed diffuse
      and nodular cortical hyperplasia, adenomas, and a single case of adrenocortical
      carcinoma. The apparently benign adrenal enlargements were not associated with
      presently ascertainable biochemical disturbances in the hypothalamic-pituitary
      adrenocortical axis, and they were without radiological signs of progression
      during follow-up. The individual developing unilateral adrenocortical carcinoma
      showed rapid adrenal expansion, feminization, and an abnormal urinary steroid
      profile after 4 yr of observation for bilateral minor adrenal enlargements.
      Pancreatic endocrine tumors were significantly overrepresented and present in all
      MEN-1 individuals with adrenal involvement. In agreement with findings in
      sporadic cases, the MEN-1 adrenocortical carcinoma genome showed loss of
      constitutional heterozygosity for alleles at 17p, 13q, 11p, and 11q. The benign
      adrenal lesions retained heterozygosity for the MEN-1 locus at chromosome 11 q
      13. Despite its prevalence and malignant potential, the pituitary-independent
      adrenocortical proliferation does not appear to be a primary lesion in MEN-1, but
      might represent a secondary phenomenon, perhaps related to the pancreatic
      endocrine tumor.

PMID- 1352310
TI  - Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression in primary
      cultures of human brain microvessel endothelial cells by cytokines and
      lipopolysaccharide.
AB  - The expression of intercellular adhesion molecule-1 (ICAM-1) by human cerebral
      endothelium was studied in primary cultures of human brain microvessel
      endothelial cells following treatment with bacterial lipopolysaccharide (LPS),
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and
      interferon-gamma (IFN-gamma). Surface expression of ICAM-1 was examined with the
      immunogold silver staining technique. Intact cerebral endothelial cells
      constitutively express low levels of ICAM-1. Stimulation with LPS and cytokines
      induces upregulation of ICAM-1 which is minimal with IFN-gamma and maximal with
      LPS or a combination of IFN-gamma and TNF-alpha. Upregulation of ICAM-1
      expression is concentration- and time-dependent, is observed as early as 4 h
      following incubation and persists for up to 72 h in the continuous presence of
      LPS or cytokines. The ICAM-1 expression is not reversed by 3 days after removal
      of the LPS or cytokines. These findings may be relevant to the interactions
      between leukocytes and brain microvessel endothelial cells in inflammatory and
      demyelinating diseases of the CNS.

PMID- 1352311
TI  - Characterization of a rat retinal endothelial cell culture and the expression of
      P-glycoprotein in brain and retinal endothelium in vitro.
AB  - Retinal vascular endothelia form one aspect of the blood-retinal barrier and,
      like the blood-brain barrier, control the passage of molecules and cells into the
      parenchyma. To facilitate comparative in vitro studies, rat retinal endothelial
      cells have been cultured and characterised. Using immunocytochemical techniques,
      retinal endothelium was positive for von Willebrand's factor, tight junction
      associated polypeptide (ZO-1) and the transferrin receptor. The cells also
      expressed high-affinity uptake of acetylated low-density lipoprotein. Using the
      monoclonal antibodies JSB-1 and C219, the product of the multidrug resistance
      gene, P-glycoprotein, was found to be expressed on primary cultures of both brain
      and retinal endothelium.

PMID- 1352312
TI  - Langerhans cells, inflammation markers and human papillomavirus infections in
      benign and malignant epithelial tumors from transplant recipients.
AB  - Organ transplant recipients frequently develop warts which progress toward
      premalignant or malignant lesions after a rather long grafting period. The local
      immune responses of such lesions (warts, condyloma acuminata, actinic keratoses,
      Bowen, basal and squamous cell carcinomas) was studied in 32 frozen skin
      specimens taken from 15 male transplant recipients and compared to similar
      lesions from the normal population. We studied the expression of T cell subsets,
      Langerhans cell phenotype, HLA class 1 (beta 2-microglobulin), HLA class 2 (DR
      antigen), and intercellular adhesion molecule 1 (ICAM 1). The presence of HPV
      infection was also considered, using in situ hybridization with biotinylated
      probes in order to examine the correlation with immunological markers. In the
      dermis, the lesions from grafted patients showed a moderate to intense
      inflammatory reaction of HLA-DR-positive cells. Most of these cells were CD4+ and
      CD8+ without any predominance of a single T cell subset. In the epidermis, most
      lesions were characterized by a reduced number of CD1-positive cells; this was
      concomitant with a decrease or a loss of beta 2-microglobulin expression by
      epithelial cells. HLA-DR antigen was not expressed by keratinocytes or tumoral
      cells in any specimen; ICAM 1 antigen was observed in a few cases. The expression
      of these markers was similarly modified with or without the presence of HPV DNA.
      Conversely, most lesions from non-immunocompromised patients, except warts,
      showed intense inflammatory reactions, with a predominance of CD4-positive cells
      and large foci of ICAM 1-positive cells. Expression of activation markers by
      keratinocytes occurred mainly in condylomas and squamous cell carcinomas. In the
      normal population, HPV infection was only detected in papilloma lesions. These
      data indicate, in lesions from grafted patients, a lack of effective immune
      response with partial inhibition of activation markers expressed by
      keratinocytes. It is conceivable that immunosuppressive treatment with solar
      exposure may also be responsible for the local immune deficiency and thus for the
      conversion of benign warts toward malignant lesions in grafted patients.

PMID- 1352314
TI  - Nutrition in the pediatric age group and later cardiovascular disease. Workshop.
      Baden/Vienna, September 17-18, 1990.

PMID- 1352313
TI  - The effects of interferon-beta on phorbol ester or calcium ionophore-induced
      intercellular adhesion molecule-I expression in epidermal carcinoma cells.
AB  - Keratinocyte intercellular adhesion molecule (ICAM)-I expression is induced by
      interferon (IFN)-gamma. It has been previously reported that IFN-beta suppresses
      IFN-gamma-induced ICAM-I expression in A431 cells, a human squamous cell
      carcinoma cell line. In this study, the suppression mechanisms were investigated
      at the post second messenger level. Both 12-O-tetradecanoylphorbol-13-acetate
      (TPA) and calcium ionophore (A23187) induce ICAM-I expression in A431 cells. ICAM
      I expression induced by either was not suppressed with cotreatment with IFN-beta.
      Furthermore, IFN-beta did not inhibit the translocation of protein kinase C (PKC)
      by TPA. It appears that the pathways involved in ICAM-I expression induced by
      activation of PKC or increased in intracellular Ca++ are not affected by IFN
      beta.

PMID- 1352315
TI  - Quantitative image cytometry of hepatocytes expressing gamma-glutamyl
      transpeptidase and glutathione S-transferase in diethylnitrosamine-initiated rats
      treated with phenobarbital and/or phthalate esters.
AB  - Image cytometry was used to quantify the volume of liver expressing two
      histochemical markers associated with neoplasia, gamma-glutamyl transpeptidase
      (GGT) and the placental isozyme of glutathione S-transferase (GST-P). Rats were
      treated with diethylnitrosamine (DENA) followed by phenobarbital (PB), di(2
      ethylhexyl)phthalate (DEHP), or di-n-octyl-phthalate (DOP) for 26 weeks. In one
      series, PB-treated rats were given 2.0%, 0.5%, or 0.1% DEHP in the feed. GGT
      expression was detected diffusely throughout the liver parenchyma in several
      treatment groups so that any enhanced expression in altered foci (AF) and nodules
      (N) was not apparent. GST-P was detected only in AF and N. GST-P may represent a
      second genetic alteration, as GST-P+ AF and N also expressed GGT but not the
      reverse. The peroxisome proliferator DEHP inhibited expression of GGT or GST-P in
      livers of either DENA-treated or DENA+PB-treated rats. With GST-P the reduction
      was correlated to a reduced number of AF and N. In contrast, DEHP's stereoisomer,
      DOP, was as effective as PB in promoting expression of both markers. We conclude
      that image cytometry of hepatocytes expressing GST-P can be used in the bioassay
      of the carcinogenic potential of chemicals that affect liver proliferation.

PMID- 1352317
TI  - Anti-hantavirus antibodies in human sera in Czechoslovakia.
AB  - By indirect immunofluorescence using antigens of hantavirus Hantaan and CG 18-20
      on Vero E6 cells were examined 5,827 samples of sera from 5,299 probands of
      Czechoslovakia. In 49 persons (0.94%) were found antibodies of titres 1:32 and
      higher. Two groups of elderly farm workers showed a cluster of positive
      individuals amounting to 9.9% and 29.4% respectively. The ratio of positivities
      in some other, randomly and specifically selected groups was deep below 1%. The
      partial results for the group of farmers were confirmed by RIA test. Occasionally
      antibodies only to one of the hantavirus serotypes, at other time, to both were
      found. The authors discuss the findings of antibodies of the two serotypes in
      humans as related to the evidenced existence of two hantavirus antigen serotypes
      in animals.

PMID- 1352316
TI  - Serotonin storage and chromogranins: an experimental study in rat gastric
      endocrine cells.
AB  - Chromogranins (Cg) and secretogranins (Sg) are acidic proteins localized in the
      secretory granules of a large variety of endocrine cells collectively named APUD
      cells (amine precursor uptake and decarboxylation). To examine the possible
      function of Cg/Sg as amine storage proteins, enteroendocrine cells of the rat
      gastric antral mucosa, i.e., serotonin-containing enterochromaffin (EC)-cells,
      gastrin (G)-, and somatostatin (D)-cells, were investigated immunohistochemically
      in serial semi-thin sections of controls and after intervention in serotonin
      synthesis. CgA and CgB immunoreactivity was determined semiquantitatively by
      optical density measurements. Experiments included inhibition of serotonin
      synthesis by p-chlorophenylalanine (pCPA), exogenous application of the serotonin
      precursor 5-hydroxytryptophan (5-HTP), and a combination of both treatments. The
      cellular distribution of Cg and the density of its immunoreactivity were closely
      related to the primary content of serotonin and the ability to store serotonin
      after 5-HTP application. Thus, Cg may act as amine-binding proteins in
      enteroendocrine cells, binding most probably being due to ionic interactions
      between Cg and the biogenic amines. EC- and G-cells, however, differed in their
      amine-handling properties and in the response of their Cg immunoreactivity after
      intervention in serotonin synthesis. We conclude, therefore, that the
      physiological function of Cg as amine storage proteins is restricted to endocrine
      cells with an endogenous content of amines. In other endocrine cells, exhibiting
      only a potential amine production, APUD may be considered as a kind of supravital
      staining without physiological significance.

PMID- 1352318
TI  - Characterization and toxicity to mosquito larvae of four Bacillus sphaericus
      strains isolated from Brazilian soils.
AB  - Four Bacillus sphaericus strains, S1, S2, S5, and L2, isolated from Brazilian
      soils, were found to be toxic to larvae of the mosquitoes Culex pipiens and
      Anopheles stephensi at a level similar to that of strain 2362 which is now used
      operationally. Like strain 2362, the four strains belonged to the serotype H5 and
      produced major proteins of apparent molecular weights of 125, 110, 56, and 43
      kDa. These latter two proteins were immunologically related to toxins of the same
      molecular weight as B. sphaericus 2362. Although the four Brazilian strains were
      very similar to strain 2362, gas chromatography analysis of the fatty acids
      revealed that these strains were different from strain 2362 and from each other,
      except for a possible similarity between strains S1 and S5.

PMID- 1352319
TI  - Genomic variations in mosquitocidal strains of Bacillus sphaericus detected by
      M13 DNA fingerprinting.
AB  - The genomic variation of Bacillus sphaericus reference and local strains
      belonging to different serotypes was examined by DNA fingerprinting. A phage M13
      DNA probe detected a number of variable fragments in the restriction digests of
      total strain DNAs. The patterns of band distribution showed a certain homology
      among mosquitocidal strains, expressed by similarity index D and might be a
      reliable criterion for assessing the level of genomic similarity between closely
      related strains. An important advantage of DNA fingerprinting is the
      differentiation of one bacterial strain from another, both expressing common
      phenotype and possessing highly similar genomic portions. The strain variation
      revealed by the M13 probe will be useful for characterization of individual
      strains within a serotype. It could help as well to solve some uncertain cases
      based on the results obtained by other methods of identification.

PMID- 1352320
TI  - [ATP receptor and neurotransmitter release].

PMID- 1352321
TI  - [Proliferative activity of endometrial cells and endometrial cancer cells using
      the monoclonal antibody PCNA].

PMID- 1352322
TI  - Characterization of two new point mutations in the low density lipoprotein
      receptor genes of an English patient with homozygous familial
      hypercholesterolemia.
AB  - Two new point mutations have been detected in the low density lipoprotein (LDL)
      receptor gene of a patient with a clinical diagnosis of homozygous familial
      hypercholesterolemia (FH). The patient is a compound heterozygote, in whom the
      mutant allele inherited from his English father has a single base substitution of
      A for G in exon 3, changing the codon for residue 80 in the mature protein from
      glutamic acid to lysine. The mutant allele inherited from his mother, who is of
      Irish origin, has a single base pair deletion in the codon for residue 743 in
      exon 15 that causes a frameshift and introduces a new stop codon in the adjacent
      position. The glu80 to lys mutation results in a transport-defective phenotype
      and a mature protein that migrates abnormally slowly on nonreduced SDS-PAGE, but
      normally under reducing conditions; this was confirmed by site-directed
      mutagenesis and expression in vitro. The deletion in exon 15 results in a null
      phenotype in which the putative truncated receptor protein cannot be detected in
      cultured skin fibroblasts and the amount of mRNA derived from the allele is
      reduced. The glu80 to lys mutation was found in a further five unrelated
      individuals in a sample of 200 FH patients from the London area and in 11 from a
      sample of 77 FH patients from Manchester. Haplotype analysis suggested that all
      the patients had inherited this allele from a common ancestor. The deletion in
      exon 15 was not found in the London sample, nor in any unrelated individuals in
      the Manchester sample.

PMID- 1352323
TI  - Genetic and dietary interactions in the regulation of HMG-CoA reductase gene
      expression.
AB  - Inbred strains of mice exhibit large genetic variations in hepatic 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase activity. A tissue-specific genetic
      variation between the strains BALB/c and C57BL/6, resulting in about 5-fold
      higher levels in hepatic reductase activity in strain C57BL/6, was examined in
      detail. The activity difference between these two strains could be explained
      entirely by differences in hepatic reductase mRNA levels. In genetic crosses, the
      variation segregated as a single major Mendelian element. Surprisingly, the mode
      of inheritance was recessive since F1 mice exhibited the BALB/c levels of enzyme
      activity. Despite the fact that the rates of hepatic sterol synthesis also
      differed between the strains by a factor of about five, the altered hepatic
      reductase expression did not significantly influence plasma lipoprotein levels.
      The response to a high cholesterol, high fat diet between the strains was
      remarkably different. Thus, in BALB/c mice, both hepatic reductase activity and
      mRNA levels were affected only slightly, if at all, by cholesterol feeding, while
      in strain C57BL/6 mice both were reduced more than 10-fold by cholesterol
      feeding. Several lines of evidence, including analysis of cis-acting regulatory
      elements, the nonadditive mode of inheritance, and genetic studies of the HMG-CoA
      reductase gene locus on mouse chromosome 13, support the possibility that the
      variation in reductase expression is not due to a mutation of the structural gene
      but, rather, is determined by a trans-acting factor controlling reductase mRNA
      levels. The variation provides a striking example, at the molecular level, of the
      importance of dietary-genetic interactions in the control of cholesterol
      metabolism.

PMID- 1352324
TI  - Diabetes incidence in users and non-users of antihypertensive drugs in relation
      to serum insulin, glucose tolerance and degree of adiposity: a 12-year
      prospective population study of women in Gothenburg, Sweden.
AB  - As part of a prospective population study in Gothenburg, Sweden, women aged 50
      years were subjected to an intravenous glucose tolerance test on entry to the
      study and followed up for 12 years. Manifest diabetes was the only end-point
      registered in this part of the study. Of 352 initially non-diabetic women, 17
      (4.8%) subjects developed diabetes, with a fourfold increased risk in women
      taking antihypertensive drugs (diuretics or beta-blockers, or both) compared with
      women who were not taking such medication. The increased risk was observed
      independently of initially measured glucose metabolism variables and degree of
      adiposity, although the incidences were higher overall if the use of
      antihypertensive drugs was combined with fasting hyperinsulinaemia and adiposity.
      This study provides further evidence to support the view that diuretics and beta
      blockers are precipitators of type 2 diabetes mellitus.

PMID- 1352325
TI  - Dural arteriovenous malformation of the transverse sinus with sinus occlusion:
      report of a case.
AB  - We report a case of dural arteriovenous malformation (AVM) of the transverse
      sinus with sinus occlusion. This 49-year-old man developed right parietal lobe
      dysfunction with acute onset. Computed tomography and magnetic resonance imaging
      (MRI) showed a non-hemorrhagic venous infarct in the subcortical white matter of
      the right parietal lobe, and diffusely dilated subcortical veins. Thrombosis of
      the right internal jugular bulb was also revealed on MRI. Cerebral angiography
      showed a dural AVM in the posterior fossa with occlusion of the right transverse
      sinus and retrograde venous drainage into the superior sagittal sinus, causing
      diffuse engorgement of the superficial cortical and the deep intramedullary
      veins. The focal neurologic deficits in this case were due to a non-hemorrhagic
      venous infarct in the subcortical white matter of the right parietal lobe
      secondary to retrograde cortical venous drainage.

PMID- 1352326
TI  - Pseudoathetosis as a presenting symptom of spinal multiple sclerosis.
AB  - We report on a 38-year-old female patient with acute proprioceptive sensory
      impairment and pseudoathetosis in the four limbs, particularly in the fingers of
      both hands. She had great difficulty in buttoning, unbuttoning, using chopsticks
      and writing, because she was no longer able to feel her fingers in space. There
      was a profound loss of position and vibration sensation in all limbs, especially
      in both hands. Pseudoathetoid movement, a rare presentation of multiple
      sclerosis, was observed in the outstretched hands and extended fingers. T1- and
      T2-weighted magnetic resonance imaging (MRI) of the spinal cord revealed an
      inactive intramedullary lesion in the C2-C5 segments. Gadolinium-enhanced MRI
      revealed an active lesion in the posterior columns of the cervical cord at the C3
      vertebral level, which is very likely responsible for pseudoathetoid movement.
      Based on the disseminated lesions in the spinal cord verified by MRI the four
      neurologic manifestations, and the abnormal somatosensory-evoked potentials, we
      made a definitive diagnosis of multiple sclerosis of the spinal cord.

PMID- 1352329
TI  - Motor-evoked potentials in diabetes mellitus.
AB  - By using magnetic stimulation of the motor cortex and in the cervical region,
      conduction time in the central motor pathway was measured in 35 patients with
      diabetes mellitus (DM) and in 41 control subjects. Motor-evoked potentials (MEPs)
      were recorded from the contralateral thenar muscles. Central conduction time
      (CCT) was obtained by subtracting the latency of the spinal MEP from that of the
      scalp MEP. To compare central and peripheral nerve functions, the motor nerve
      conduction velocity (MCV) of the median nerve was also tested in patients with
      DM. In the 35 cases of DM, the mean latency of the cortical MEPs showed a
      significant increase, compared with normal controls; the mean CCT was also
      significantly prolonged in the patient group. There was a good correlation
      between central motor abnormalities and the duration of DM, as well as with
      impairment of the peripheral nervous system. Latencies of greater than two
      standard deviations were defined as abnormal. The abnormal rate in patients with
      DM was 29% for latency of the cortical MEP, 20% for latency of the cervical MEP
      and 37% for the CCT. In addition, there was a 35% abnormal rate for distal
      latency of the median MCV and a 40% abnormal rate for the median MCV. These
      findings support the theory that the metabolic disturbance in DM affects both the
      central and peripheral nervous systems in man. MEP studies provide objective
      measurements of central motor pathways.

PMID- 1352327
TI  - Brachial plexus neuropathy associated with scrub typhus: report of a case.
AB  - We report on a 20-year-old man who had scrub typhus with the unusual neurologic
      complication of brachial plexus neuropathy. The clinical features of fever,
      headache, pneumonitis, eschar, high Weil-Felix OX-K agglutination and Rickettsia
      tsutsugamushi immunofluorescence titers confirmed the diagnosis of scrub typhus.
      Brachial plexus neuropathy was proven by an electrophysiologic examination. He
      had a nearly complete recovery after adequate medical treatment.

PMID- 1352330
TI  - Reduction of herniated temporal lobe in patients with severe head injury and
      uncal herniation.
AB  - Thirty-two patients with severe head injury (Glasgow coma scale 5-7/15) and uncal
      herniation were treated surgically from January 1988 to June 1990. Reduction of
      the herniated temporal lobe in addition to classical surgical procedures
      (craniotomy with evacuation of hematoma and resection of the contused brain) was
      performed in 10 patients (group A). The remaining 22 patients (group B) were
      treated similarly but without reduction of the herniated temporal lobe. In group
      A, there was one operative mortality. Eight patients made a rapid and complete
      recovery of pupil size and light reflex within two days after the operation, and
      one recovered within two months after the operation. The recovery of motor
      strength was also rapid in these nine patients. After three to 20 months
      (average, 11 months) of follow-up, the outcome was good in two patients, and the
      other seven were moderately disabled. In group B, 12 patients (55%) died after
      the operation. When compared with group A, the surviving 10 patients made a
      slower and less satisfactory recovery of oculomotor nerve function and motor
      status, and had a worse outcome after four to 25 months (average, 14 months) of
      follow-up (moderately disabled, six patients; severely disabled, two patients;
      vegetative, two patients). From my experience, it appears that the procedure of
      reduction is simple and seems to result in a more rapid and complete recovery of
      oculomotor nerve function and motor status, and it may even contribute to a
      better overall outcome.

PMID- 1352328
TI  - Therapeutic effect of guar gum in patients with non-insulin-dependent diabetes
      mellitus.
AB  - Diets with a high-fiber content have been shown to produce some beneficial
      effects on metabolic factors in subjects with NIDDM. However, some controversies
      still exist. In this report, the long-term effect of guar gum (Guarina) on both
      glycemic and blood lipid profiles was assessed in a randomized, double-blind and
      cross-over study on 16 (seven male and nine female) subjects with NIDDM. Each
      subject received placebo (P) and Guarina (G) treatment for two eight-week periods
      separated by a four-week period to facilitate wash-out. Fasting plasma glucose
      levels showed significant improvement during G treatment but not during P
      treatment (151.7 +/- 7.9 vs 168.6 +/- 12.2 mg/dl, p less than 0.01 by paired
      Student's t test). Hemoglobin Alc levels decreased significantly during G
      treatment but not during P treatment (6.9 +/- 0.2 vs 7.2 +/- 0.8%, p less than
      0.001). Fasting insulin concentrations also showed significant lowering during G
      treatment but not during P treatment (18.3 +/- 2.1 vs 23.1 +/- 2.9 U/ml, p less
      than 0.005). Other variables, including serum total cholesterol, triglyceride,
      HDLc, LDLc, sodium, potassium, chloride, magnesium and calcium levels showed no
      significant changes during G or P treatment. Ten out of the 16 patients (62.5%)
      suffered from side effects; these included abdominal cramps (one case), diarrhea
      (seven cases) and skin itching (one case). In conclusion, guar gum effectively
      lowers fasting plasma glucose and HbAlc levels in subjects with NIDDM.
      Hyperinsulinemia could also be ameliorated. The effectiveness and side effects of
      guar gum treatment should be cautiously evaluated in each NIDDM subject.

PMID- 1352331
TI  - Effects of timolol and acetazolamide on intraocular pressure elevation following
      argon laser iridotomy.
AB  - To study the effect of hypotensive agents on intraocular pressure elevation
      following argon laser iridotomy, 0.5% timolol maleate topically and acetazolamide
      125 mg orally were given in 39 eyes, one hour prior to laser iridotomy, with 29
      eyes serving as the control. The mean pressure two hours after laser iridotomy
      was 18.9 +/- 7.2 mmHg in the control group and 12.8 +/- 3.9 mmHg in the
      pretreated group. Ocular pressure was elevated from the baseline pressure of the
      prelaser status in two eyes (5%) only in the timolol-acetazolamide treated group
      and in 16 eyes (55%) in the control group. The pressure elevation two hours after
      laser iridotomy was significantly less in the timolol-acetazolamide pretreated
      group.

PMID- 1352333
TI  - Correlation between left ventricular systolic function and dipyridamole thallium
      SPECT redistribution patterns in coronary artery disease.
AB  - The dipyridamole thallium-201 single photon emission computed tomography (SPECT)
      and resting gated blood pool ventriculography were sequentially conducted in 31
      consecutive patients with angiographically proven coronary artery disease. The
      functional significance of various thallium redistribution patterns was assessed.
      The patients with an entirely complete (CR) or partial (PR) redistribution
      pattern had a higher global left ventricular ejection fraction than those with
      combined PR and no redistribution (NR), while patients with an entirely CR
      pattern did not have a statistically better ejection fraction than those with PR.
      Furthermore, myocardial segments with normal perfusion (N) and those with CR or
      PR had a higher regional ejection fraction than those with NR in the infero
      apical area and the septal area. The regional ejection fraction was statistically
      higher in patients with CR than in those with PR in the septal area and higher,
      though not statistically significant, in the infero-apical area. The functional
      difference between groups with N and CR was not significant. Thus, we conclude
      that the redistribution patterns of dipyridamole thallium SPECT are closely
      correlated with systole function. Myocardium, in the presence of redistribution,
      will have a better functional performance in coronary artery disease.

PMID- 1352332
TI  - T lymphocyte changes in open heart surgery.
AB  - To investigate the effect of open heart surgery on T lymphocytes and their
      subpopulations, 20 patients, who had undergone moderate- to high-dose fentanyl
      anesthesia and a cardiopulmonary bypass (CPB), were studied using flow cytometry
      techniques and monoclonal antibodies during and after surgery. The ages of these
      patients ranged from four to 61 years with eight being male and 12 being female.
      The disease entity consisted of four with coronary, six with congenital and 10
      with valvular heart disease. No cyanotic patients were included in this study.
      Peripheral blood samples were collected before anesthesia, immediately before the
      surgical incision, on the first postoperative day (POD1) and on the second
      postoperative day (POD2), respectively. We found no significant changes in the
      percentage of total T cells (T3), or helper (T4) and suppressor (T8) T cells
      during anesthesia before the surgical incision. On POD1, all T lymphocyte subset
      percentages decreased significantly when compared to pre-operative values (total
      T cells: 58.4 +/- 12.6 vs 24.4 +/- 8.4, helper T cells: 33.3 +/- 10.1 vs 15.4 +/-
      6.3, suppressor T cells: 23.0 +/- 6.4 vs 10.0 +/- 4, all p less than 0.001) but
      returned to preoperative levels on POD2. Throughout the study period, there were
      no significant changes in the T helper cell to T suppressor cell ratio. In spite
      of the transient decrease in T lymphocytes and their subpopulations, no clinical
      evidence of infection was noted in any patient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352334
TI  - Effect of estrogen on the serum level of thyroglobulin.
AB  - Thyroglobulin has been widely accepted as a useful parameter for monitoring the
      recurrence of differentiated thyroid carcinoma. In thyroid cell cultures, it has
      been reported that estrogen may stimulate the tgb gene which controls synthesis
      of thyroglobulin by the thyroid follicular cell. Since the serum estrogen levels
      of women fluctuate during the menstrual cycle, pregnancy and menopause,
      thyroglobulin may be unreliable in the follow-up of recurrence of differentiated
      thyroid carcinoma in females if it can be affected by estrogen in vivo. In order
      to clarify the effect of estrogen on thyroglobulin, the sera of 16 men, 42 women
      and 20 children were collected and divided into seven groups. Their serum
      estradiol and thyroglobulin levels were 17.7 +/- 1.8 pg/mL (mean +/- SEM) and
      17.1 +/- 1.6 ng/mL, respectively in 20 children, 26.7 +/- 4.1 pg/mL and 12.9 +/-
      1.2 ng/mL, respectively in 16 males, 151.6 +/- 20.4 pg/mL and 13.7 +/- 4.2 ng/mL,
      respectively in five females on the 10th to 14th days of the menstrual cycle,
      16.7 +/- 1.8 pg/mL and 15.2 +/- 2.1 ng/mL, respectively in 12 postmenopausal
      females, 530.0 +/- 131.0 pg/mL and 14.2 +/- 1.8 ng/mL, respectively in eight
      pregnant women in the first trimester, 3613.9 +/- 1014.2 pg/mL and 12.0 +/- 1.6
      ng/mL, respectively in seven pregnant women in the second trimester and 9246.0 +/
      694.5 pg/mL and 16.4 +/- 2.0 ng/mL, respectively in 10 pregnant women in the
      third trimester. The serum estradiol levels were significantly different (p less
      than 0.005) among these seven groups, but the serum thyroglobulin levels were not
      (p = 0.25). Therefore, serum thyroglobulin levels are not affected by
      estrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352335
TI  - Holter monitoring in patients with Wolff-Parkinson-White syndrome: with special
      reference to intermittent pre-excitation.
AB  - To characterize the intermittency of pre-excitation in patients with Wolff
      Parkinson-White syndrome (W-P-W), we studied the ambulatory electrocardiograms
      (ECGs) of 48 patients (32 men and 16 women with a mean age of 38.5 years) with W
      P-W. As documentation, at least one ECG for each patient had been performed
      during the follow-up period at our clinics. All cardiovascular drugs were
      discontinued for at least two days before Holter ECG monitoring. Through a
      careful beat-to-beat analysis of the QRS complex morphology, we were able to
      classify these patients into three groups: persistent pre-excitation in 26
      (54.2%); intermittent pre-excitation in 17 (35.4%); and no pre-excitation in five
      (10.4%). There was no significant difference in sex, frequency of arrhythmias or
      mean heart rate among the three groups. Among the 17 showing intermittent pre
      excitation, type A W-P-W was more prevalent (12 cases), and the ratio of pre
      excitation to normal beats tended to decrease with age. Conduction normalized
      gradually with an increase in heart rate in 12 patients and suddenly in five
      other cases. There were two patients who showed a period of 2:1 pre-excitation
      intermingled with 1:1 pre-excitation and 1:1 normalized beats. These changes
      occurred with equal frequency both during the daytime and at night. These
      findings suggest that intermittent pre-excitation is a rather frequent phenomenon
      in patients with W-P-W. It occurs more frequently in type A patients and in older
      patients. Therefore, it may be an intermediate phase between manifest and
      concealed W-P-W.

PMID- 1352336
TI  - Detection of mass lesions in the collapsed lung by ultrasonography.
AB  - Ultrasonography is useful in the detection of mass lesions in the collapsed lung,
      using the collapsed lungs as a "sonic window". Twenty-four patients suspected of
      having a tumor causing lung collapse, as shown on their chest radiographs, were
      examined by ultrasonography. Eighteen out of 24 patients were found to have mass
      lesions in their collapsed lungs. Thoracic computed tomography (CT) was also
      performed in 12 of these 18 patients; of those, 11 showed compatibility with
      sonographic findings in the detection of mass lesions in their collapsed lungs.
      The remaining six of these 24 patients with no mass lesions detected by
      ultrasonography were proven to have collapsed lung due to sputum impaction (n =
      2) and lung cancer (n = 4). The fact that four patients had lung cancer that was
      not detectable by ultrasonography, might have been due to relatively small mass
      lesions at deep locations (main or intermediate bronchus) and narrowing of the
      "sonic window" (partial lung collapse). Though it has some limitations,
      ultrasonography is helpful in detecting mass lesions in collapsed lungs. Sono
      guided fine needle aspiration biopsy (SGFNAB) can also be performed
      simultaneously, smoothly and without any major complications. In our series,
      SGFNAB was performed in eight out of 18 patients to make a cytopathologic
      diagnosis. We recommend this safe, convenient, and noninvasive method to screen
      for lesions in the collapsed lung, especially when bronchoscopic examination is
      impossible.

PMID- 1352337
TI  - Localization of obscure gastrointestinal bleeding by technetium 99m-labeled red
      blood cell scintigraphy.
AB  - When a bleeding source from the gastrointestinal (GI) tract cannot be identified
      with conventional diagnostic studies, it is known as GI bleeding of an obscure
      origin. In the past three years, in vivo Technetium 99m-labeled red blood cell
      scintigraphy (RBC scan) has been added to our armamentarium for the diagnosis of
      obscure GI bleeding. Out of a total of 26 cases, the bleeders could be detected
      in 12 or 46.2% by RBC scan. The time required ranged from 15 minutes to 24 hours
      (median, one hour). In 14 patients with active bleeding during the scan period,
      11 had positive scans (sensitivity, 78.6%). In 12 patients with inactive
      bleeding, 11 had negative scans (specificity, 91.7%). Angiography was conducted
      in nine cases, with all showing negative findings; however, six of them had a
      positive focus by RBC scan. Laparotomy was performed in seven scan-positive
      patients, and in three scan-negative patients because of a positive Meckel's scan
      (two cases) or recurrent bleeding (one case). Of the 12 scan-positive patients,
      incorrect localization was noted in two patients due to rapid transit of the
      labeled RBC in the small bowel. False localization could be prevented by
      shortening the sequential imaging interval. It is concluded that an RBC scan is a
      very sensitive and safe tool for detection of GI bleeding of an intermittent
      nature, because the bleeder can be monitored for 24 hours after a single
      injection. It can be used as a preangiographic screening test and to guide the
      surgeon in surgical planning or decision-making.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352338
TI  - Mechanics of acutely shortened canine diaphragm muscle in vitro.
AB  - Acute changes in lung volume, as might be seen in an airway-obstructed patient,
      may lead to different amounts of shortening of the various inspiratory muscles,
      of which the diaphragm is the most important. The purpose of this study is to
      investigate the twitch and contractile characteristics of acutely shortened
      canine diaphragm muscle in vitro during isometric contraction. We found that with
      diaphragmatic muscle shortening from Lo (optimal length, defined as being that
      length at which peak twitch tension was generated) to 70% Lo, the time-to-peak
      tension, half relaxation time and twitch tension were significantly reduced. The
      force-frequency curves, obtained from different muscle lengths, disclosed that
      shorter muscles generate disproportionately less force during low-frequency
      stimulation. These factors may, at least in part, contribute to the vulnerability
      to fatigue of those with shorter diaphragmatic muscle length.

PMID- 1352339
TI  - Conservative treatment of neonatal hydronephrosis.
AB  - From February 1990 to January 1991, 19 cases of hydronephrosis in children of
      less than one year of age were managed at Mackay Memorial Hospital. In the
      majority of these patients, there were evident causes such as ureteropelvic
      junction stenosis, ureterovesical reflux or a posterior urethral valve for which
      definite therapeutic measures were performed. However, some cases had no obvious
      origins and the hydronephrosis was speculated to be from nonobstructive or
      physiologic dilatation of the kidneys. The conventional tools, such as
      intravenous pyelogram or renal ultrasound, which comprise the mainstay of
      diagnosis, provide limited information on renal functional status. Recent
      introduction of the Tc-99m diethylene triamine penta-acetic acid (DTPA) diuretic
      renal scan has enabled us to distinguish between obstructive and nonobstructive
      hydronephrosis and helps us to determine whether or not surgery is necessary. In
      the past year, eight patients with hydronephrosis of less than one year of age
      were diagnosed as nonobstructive after a series of evaluations using renal
      ultrasound, voiding cystourethrography (VCUG) and Tc-99m DTPA diuretic renal
      scan. Follow-up studies by echography or DTPA renal scan revealed spontaneous
      resolution of the dilated collecting systems in these cases and confirms our
      belief that some hydronephrosis in neonates and infants may resolve spontaneously
      and may just be a manifestation of physiologic change during development. The
      value of the Tc-99m DTPA diuretic renal scan in the diagnosis of obstructive
      uropathy is discussed.

PMID- 1352340
TI  - Helicobacter pylori, gastritis and duodenitis in the healing process of duodenal
      ulcer.
AB  - The occurrence of antral gastritis, duodenitis, gastric metaplasia and
      Helicobacter pylori (H. pylori) were compared between 63 endoscopically proven
      duodenal ulcer (DU) patients and 34 non-ulcer dyspepsia (NUD) patients with no
      ulcer history and no ulcer present as documented by endoscopy. The DU group
      showed a significantly higher rate of active antral gastritis (89% vs 41% p less
      than 0.05), a higher antral H. pylori carrying rate (76% vs 27% p less than
      0.01), a higher rate of active chronic duodenitis (75% vs 32% p less than 0.05),
      and a higher rate of gastric metaplasia in the duodenal bulb (68% vs 27% p less
      than 0.05) than the NUD group. The H. pylori carrying rate in the bulb was 16% in
      the DU group and 0% in the NUD group. The difference is evident, although it is
      statistically insignificant. All 10 cases carrying H. pylori in the duodenum in
      the DU group had active chronic duodenitis with gastric metaplasia. Further
      evaluation of the variables (rate of active antral gastritis and duodenitis and
      the carrying rate of H. pylori in the antrum and bulb) showed no difference
      between different ulcer stages (active, healing, or scarred). The above findings
      strongly suggest a close relation between H. pylori and duodenal ulcer. However,
      the low occurrence rate of the bacteria in the bulb can only indicate a partial
      etiologic role of the bacteria in DU. No improvement in antral gastritis,
      duodenitis and H. pylori occurrence, despite the healing of an ulcer, is in
      agreement with the naturally high recurrence rate of duodenal ulcers.

PMID- 1352341
TI  - Infantile osteopetrosis: report of two cases.
AB  - Two cases of infantile osteopetrosis are reported. Both were males aged four and
      eight months at presentation. They presented with osteosclerotic change of the
      bone, leukoerythroblastic anemia, optic atrophy, hepatosplenomegaly and frequent
      infection. The histology of the bone showed thickened bone trabeculae with little
      osteoclastic activity, although in one patient the number of osteoclasts
      increased, while in the other they did not. One received a bone marrow transplant
      (BMT) but died from disseminated cytomegaloviral infection, pulmonary hemorrhage
      and sepsis. The post-transplant marrow histology showed evidence of engraftment
      and osteoclastic activity. The other only received a course of prednisolone,
      which was of little help. His condition has followed a natural course with
      progressive visual impairment and marrow failure. Our cases suggest that
      infantile osteopetrosis should be taken into consideration in dealing with
      infants who present with early marrow failure and that patients of infantile
      osteopetrosis should receive BMT. BMTs appear to be the only cure. They should be
      given as early as possible to avoid major consequences and severe infection.

PMID- 1352342
TI  - Purification of radioiodinated human insulin by high performance liquid
      chromatography for a sensitive radioimmunoassay.
AB  - The optimal sensitivity of a radioimmunoassay depends on the purity of the
      radiolabeled antigen. The conventional purification methods are not complete and
      are time consuming. The combination of a Sep-pak C18 cartridge and high
      performance liquid chromatography (HPLC) for the purification of 125I-labeled
      insulin in our study revealed that the Sep-pak cartridge can serve as the
      preliminary step to remove unreacted radioactive iodide, the reactants, and
      labeled but presumably damaged materials unadsorbed to the cartridge. The
      fractions eluted from the Sep-pak containing high radioactivity and high
      immunoreactivity to the antibody were chosen for further purification by HPLC to
      eliminate undesirable radiolabeled substances with a lesser immunoreactivity. The
      purified radiolabeled insulin was used to develop a sensitive radioimmunoassay
      with detecting limits of 0.03 microU/mL per tube.

PMID- 1352343
TI  - Bilateral severance of thumbs: report of two cases.
AB  - Management of hand injuries is a common practice but bilateral amputation of
      thumbs is very rare. We report on two cases of both thumbs amputated by a similar
      machine. In case 1, the man's left thumb was closed with a composite skin graft
      because the severance was through the middle of the nail. A wrap-around procedure
      was performed to reconstruct the right thumb which was infected after a primary V
      Y advancement flap. The final results were acceptable. Replantation of detached
      thumbs, if possible, achieves the best functional recovery, which was well
      demonstrated in Case 2. Although the interphalangeal joints were arthrodesed, the
      patient was greatly satisfied with the results because of excellent appearance,
      adequate strength and nearly normal sensation. Prevention of bilateral thumb
      injuries is important. The paper-cutting machine on which these accidents
      occurred should be improved in order to prevent further similar catastrophes.

PMID- 1352345
TI  - Simultaneous bilateral tubal pregnancies after in vitro fertilization and embryo
      transfer: report of a case.
AB  - Ectopic pregnancies continue to be a major complication of in vitro fertilization
      and embryo transfer (IVF-ET). A case of bilateral simultaneous tubal pregnancy
      after IVF-ET is described. The patient underwent ovum pick-up (OPU) through a
      laparotomy with concomitant pelvic surgery. Embryo transfer (ET) was performed
      two days after OPU; this resulted in bilateral tubal pregnancies, diagnosed and
      treated one month apart. There are several possible causal mechanisms for the
      increased rate of ectopic pregnancies following IVF-ET. It is important to
      recognize that care in the transfer technique, with respect to the catheter
      position and limiting the volume of transfer medium to 20 microL, and an
      awareness of previous occlusion of the tubal ostia, or of a salpingectomy before
      IVF-ET, can help to minimize this complication rate. Two important points are the
      possibility of a simultaneous bilateral tubal pregnancy after IVF-ET, and the
      necessity of carefully examining both adnexa at the time of surgery for an
      ectopic pregnancy. Early and accurate diagnosis of a simultaneous bilateral
      ectopic pregnancy can prevent the necessity of a second operation and reduce
      maternal morbidity and mortality.

PMID- 1352344
TI  - Lymphokinetic monitoring of a liver transplant recipient treated with OKT3.
AB  - Orthotopic liver transplantation was performed on a 48-year-old female patient
      with end-stage liver disease due to primary biliary cirrhosis. A course of OKT3
      (5 mg/kg intravenously for 14 days) was given as immunosuppressive therapy.
      Lymphocyte population, T lymphocyte subsets and the lymphokine level in the
      peripheral blood were serially measured. Total T cells disappeared in the
      peripheral circulation within 10 minutes after an injection of OKT3. Helper T
      cells and suppressor T cells were also suppressed during the course of treatment.
      The ratio of T4/T8 declined from 2.5 to around 1.3. The serum interleukin-2 and
      the interleukin-2 receptor did not change markedly during treatment. The serum
      neopterin level increased after discontinuation of OKT3. The anti-mouse OKT3
      antibody increased after the ninth day of OKT3 treatment. OKT3 showed potent T
      cell suppressive activity.

PMID- 1352346
TI  - Dietary alpha-linolenic acid deficiency and early uterine development in female
      rats.
AB  - Feeding rats a purified diet containing peanut oil with a low alpha-linolenic
      acid [18:3(n-3)] content resulted in lower amounts of (n-3) polyunsaturated fatty
      acids, mainly docosahexaenoic acid [22:6(n-3)], greater amounts of
      docosapentaenoic acid [22:5(n-6)] in uterus phospholipids, and altered postnatal
      uterus development when compared with rats fed a diet containing peanut and
      rapeseed oils. Maximal differences in uterine growth, as measured by uterine
      weight, protein and DNA content, occurred between d 24 and 30 postpartum and
      disappeared near the end of sexual development (d 40). The induction of the
      progesterone receptor was not affected, and serum estradiol concentrations were
      not significantly reduced in deficient animals. Moreover, growth response of the
      uterus to low doses of 17 beta-estradiol (less than 5 micrograms/kg) was
      significantly reduced in ovariectomized animals fed the diet containing only
      peanut oil. However, the maximal response of the uterus, observed with higher 17
      beta-estradiol doses (5-50 micrograms/kg), was not affected. Because the two
      diets used differed in the content of alpha-linolenic acid, it is likely that
      alpha-linolenic acid deficiency in animals fed the diet containing only peanut
      oil was the cause of the affected uterine development.

PMID- 1352347
TI  - Work-related injuries to the foot. Data from an occupational injury/illness
      surveillance system.
AB  - In 1988, a total of 990 work-related injuries to the foot of employees from
      private-sector companies were characterized in an occupational injury/illness
      surveillance system maintained by a network of occupational health centers. The
      mean age of the worker with a foot injury was 34.2 years (+/- 12.0), with 83%
      occurring among men; 22.3% of the cases were fractures or sprains/strains. Jobs
      involving extensive manual material handling or vehicular operations were the
      most often listed occupations among those with work-related foot injuries. Across
      occupational groups, being struck by an object accounted for 58.4% of the foot
      injuries. Regardless of industry group, metal items and vehicles were related to
      50.7% of all work-related foot injuries. Specifically, foot injuries were found
      to be associated with being struck by boxes, metals, or vehicles, or to being
      caught in, under, or between vehicles or machinery. A peak of work-related
      injuries involving the foot is observed during the summer months.

PMID- 1352348
TI  - Prescribing and use of benzodiazepines: an epidemiologic perspective.

PMID- 1352349
TI  - Controversies in pediatric gastroesophageal reflux.

PMID- 1352350
TI  - Comparative study of interaction mode of diazepines with human serum albumin and
      alpha 1-acid glycoprotein.
AB  - The binding of nine diazepines to human serum albumin (HSA) and to alpha 1-acid
      glycoprotein (AGP) was investigated by means of fluorescence and circular
      dichroism (CD) spectroscopies. The binding parameters of diazepam obtained from
      fluorescence agreed with those obtained from CD measurements. Diazepines have one
      tight binding site on both HSA and AGP. The binding parameters (nK) of the
      diazepine: HSA systems are slightly higher than those of diazepine:AGP systems.
      The relationship between the binding parameters for these two serum proteins and
      the physicochemical parameters of diazepines was studied by multiple regression
      analysis to elucidate the binding mode. Moreover, the effects of long-chain fatty
      acids and cesium chloride on the binding of diazepines to HSA and AGP were also
      studied. The driving force for the binding of diazepines to both proteins appears
      to be hydrophobic interaction. In addition, steric effects and electrostatic
      interactions may also contribute to the binding of diazepines to HSA and AGP,
      respectively.

PMID- 1352351
TI  - Synthesis and antiulcer activity of N-substituted N'-[3-[3
      (piperidinomethyl)phenoxy]propyl]ureas: histamine H2-receptor antagonists with a
      potent mucosal protective activity.
AB  - As an aim toward developing new antiulcer agents, new N-substituted N'-[3-[3
      (piperidinomethyl)phenoxy]propyl]ureas were synthesized and evaluated for
      histamine H2-receptor antagonistic, gastric antisecretory, and gastric mucosal
      protective activities. A QSAR study showed that the most favorable N-substituents
      were electron-donating straight-chain alkyl groups of short length such as ethyl
      group from the viewpoint of dual action, i.e., gastric antisecretory and mucosal
      protective actions. Among the ureas studied, compounds 4, 5, and 8-10 were
      selected as candidates for further study.

PMID- 1352352
TI  - "Mixed inhibitor-prodrug" as a new approach toward systemically active inhibitors
      of enkephalin-degrading enzymes.
AB  - In order to evaluate the possible advantages of potentiating the effects of the
      endogenous enkephalins, to obtain analgesia without the serious drawbacks of
      morphine, it was essential to design systemically active compounds which inhibit
      the two metabolizing enzymes, aminopeptidase N (APN) and neutral endopeptidase
      24.11 (NEP). A new concept combining the idea of "prodrug" and "mixed inhibitor"
      was therefore developed. Given the high efficiency of beta-mercaptoalkylamines as
      APN inhibitors and of N-(mercaptoacyl) amino acids as NEP inhibitors, compounds
      associating these molecules through disulfide or thioester bonds, which are known
      to increase lipophilicity and to favor passage across the blood-brain barrier,
      have been synthesized. An HPLC study indicated that the disulfide bridge was
      resistant to serum enzymes but was cleaved by brain membrane homogenates,
      suggesting that the active inhibitors were released in the central nervous
      system. The validity of the approach was verified by the efficient
      antinociceptive responses obtained in the hot plate test in mice after iv
      administration of disulfide-containing inhibitors (ED50s of from 4 to 26 mg/kg on
      the jump latency time). The analgesic potencies of the "mixed inhibitor-prodrug"
      RB 101 [H2NCH(CH2CH2SCH3)CH2SSCH2CH(CH2Ph)CONHCH( CH2Ph)COOCH2Ph] after iv
      administration were three times greater than those of a similar combined dose of
      its two constitutive moieties. The separation of the two diastereoisomers
      constituting RB 101 showed that the analgesia has a stereochemical dependence,
      the (S,S,S)-isomer being more active than the (S,R,S)-isomer. Furthermore, in the
      tail flick test in the rat, RB 101 gave 38% analgesia at a dose of 80 mg/kg. Due
      to its high efficiency and its longer pharmacological effect, RB 101 was selected
      for a complete study of its analgesic properties.

PMID- 1352353
TI  - New triazine derivatives as potent modulators of multidrug resistance.
AB  - A series of 70 triazine derivatives have been synthesized and tested for their
      capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells
      in vitro, in comparison with verapamil (VRP), a calcium channel antagonist
      currently used in therapy as an antihypertensive drug, which also shows MDR
      modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR
      reversing properties in vitro (300- and 6-fold VRP at 5 microM in DC-3F/AD and KB
      A1 cells, respectively) and induced a strong accumulation of adriamycin. The
      relationship between the increase of ADR accumulation and the fold reversal
      induced by these compounds and their lack of effects on the sensitive DC-3F cells
      suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed
      efflux of cytotoxic agents, as already described for a majority of MDR
      modulators. In vivo, in association with the antitumor drug vincristine (0.25
      mg/kg), 16 (100 mg/kg) increased the T/C by 39% in mice bearing the resistant
      tumor cell line P388/VCR. According to these interesting properties, 16 was
      selected for a clinical development because it was more bioavailable than 34,
      even though it was less active.

PMID- 1352354
TI  - Confirmation of an association between RFLPs at the transforming growth factor
      alpha locus and non-syndromic cleft lip and palate.
AB  - Three RFLPs at the TGFA locus were studied in 60 unrelated British Caucasian
      subjects with non-syndromic cleft lip/palate and 60 controls. A highly
      significant association between the TaqI RFLP and the occurrence of clefting was
      found (chi 2 = 15.04, p = less than 0.001). No significant association was found
      with the two other RFLPs studied (BamHI and RsaI). Haplotypes derived from the
      three RFLPs at the TGFA locus also showed an over-representation of the C2A2B2
      haplotype in cases compared to controls. Analyses of genotypes according to type
      of cleft and the presence or absence of a family history of clefting were also
      carried out. These results provide further support for the role of TGFA as a gene
      of major effect in the development of orofacial clefts in humans.

PMID- 1352355
TI  - No evidence of linkage between the transforming growth factor-alpha gene in
      families with apparently autosomal dominant inheritance of cleft lip and palate.
AB  - Eight families have been identified with cleft lip, with or without cleft palate
      (CL/P), inherited in an apparently autosomal dominant manner. Transforming growth
      factor-alpha (TGFA) has been tested as a candidate gene for clefting in these
      families. Negative lod scores were generated in an autosomal dominant model with
      80% penetrance (Z = -3.152 at theta = 0.05 and Z = -2.49 at theta = 0.05 with
      only affected subjects scored). After testing with a reduced penetrance of 28%,
      less negative lod scores were generated (Z = -0.157 at theta = 0.00), but there
      was still no evidence of linkage. An autosomal recessive model with a penetrance
      of 35% was also tested. Regardless of the model used there was little evidence of
      linkage between TGFA and the CL/P phenotype, which is in contrast to the
      previously published findings of an association between TGFA and CL/P in
      unrelated subjects.

PMID- 1352356
TI  - Terminal 22q deletion associated with a partial deficiency of arylsulphatase A.
AB  - A 7 month old girl with psychomotor retardation, hypotonia, and minor
      malformations was found to have a terminal deletion of the long arm of chromosome
      22, del(22)(q13.31). The partial deficiency of arylsulphatase A (ARSA) and the
      normal level of NADH diaphorase 1 (DIA1) suggests that the ARSA locus can be
      regionally assigned to 22q13.31----qter and the DIA1 locus can be excluded from
      the same segment. This report is the third published case with a terminal 22q
      deletion.

PMID- 1352357
TI  - Low resolution structure of microtubules in solution. Synchrotron X-ray
      scattering and electron microscopy of taxol-induced microtubules assembled from
      purified tubulin in comparison with glycerol and MAP-induced microtubules.
AB  - The structure of microtubules has been characterized to 3 nm resolution employing
      time-resolved X-ray scattering. This has revealed detailed structural features of
      microtubules not observed before in solution. The polymerization of highly
      purified tubulin, induced by the antitumour drug taxol, has been employed as a
      microtubule model system. This assembly reaction requires Mg2+, is optimal at a
      1:1 taxol to tubulin heterodimer molar ratio, proceeds with GTP or GDP and is
      intrinsically reversible. The X-ray scattering profiles are consistent with
      identical non-globular alpha and beta-tubulin monomers ordered within the known
      helical surface lattice of microtubules. Purified tubulin-taxol microtubules have
      a smaller mean diameter (approx. 22 nm) than those induced by microtubule
      associated proteins or glycerol (approx. 24 nm), but nearly identical wall
      substructure to the resolution of the measurements. This is because the majority
      of the former consist of only 12 protofilaments instead of the typical 13
      protofilaments, as confirmed by electron microscopy of thin-sectioned, negatively
      stained and ice-embedded taxol microtubules. It may be concluded that taxol
      induces a slight reduction of the lateral contact curvature between tubulin
      monomers. The main fringe pattern observed in cryo-electron micrographs is
      consistent with a simple 12 protofilament 3-start skewed lattice model.
      Cylindrical closure of this lattice can be achieved by tilting the lattice 0.8
      degrees with respect to the microtubule axis. The closure implies a discontinuity
      in the type of lateral contacts between the tubulin monomers (regardless of
      whether these are of the -alpha-beta- or the -alpha-alpha-/-beta-beta- type),
      which indicates that lateral contacts and the subunit specificity of taxol
      binding are, to a large degree, equivalent.

PMID- 1352358
TI  - Diving for drugs: scientists search the sea.

PMID- 1352359
TI  - Association of overexpression of tumor suppressor protein p53 with rapid cell
      proliferation and poor prognosis in node-negative breast cancer patients.
AB  - BACKGROUND: Recent evidence indicates that a subset of axillary node-negative
      (ANN) breast cancer patients can benefit from adjuvant therapy. Reliable
      prognostic markers are needed, however, to help clinicians identify these
      patients and arrive at more rational treatment decisions. PURPOSE: Mutations of
      the p53 tumor suppressor gene often result in overexpression of the p53 protein.
      In this study, we evaluated the prognostic significance of p53 protein
      overexpression in patients with ANN breast cancer. We also studied the
      association between the tumor cell proliferation rate and overexpression of the
      p53 and c-erbB-2 proteins, both of which have been implicated in cell cycle
      control. The c-erbB-2 protein is the product of the ERBB2 gene. METHODS: Two
      hundred eighty-nine ANN cases were randomly selected from a population-based
      cohort of patients who had not received any kind of adjuvant chemotherapy or
      endocrine therapy. Overexpression of the p53 and c-erbB-2 proteins was studied
      immunohistochemically in archival paraffin-embedded tumor samples, using the CM-1
      polyclonal and the TAb 250 monoclonal antibodies, respectively. The tumor cell
      proliferation rate was measured as the S-phase fraction by DNA flow cytometry.
      Statistical analyses were performed using BMDP software. RESULTS: High-level p53
      protein overexpression, found in 41 of the 289 tumors, was most common in tumors
      with high histologic grade, negative estrogen receptor status, c-erbB-2 protein
      overexpression, DNA index greater than 1.3, or high S-phase fraction. The lowest
      S-phase levels were found in tumors with neither p53 nor c-erbB-2 protein
      overexpression; the highest levels were seen in tumors showing overexpression of
      both proteins (P less than .0001). Both p53 and c-erbB-2 overexpression, as well
      as tumor size, had independent prognostic value in multivariate analysis. Eight
      year survival of patients with p53 protein overexpression was 56% compared with
      81% in patients with no overexpression (relative risk, 3.7; P less than .0001).
      If the S-phase fraction was included in a Cox regression analysis, however, only
      the tumor size and the S-phase fraction emerged as independent predictors of
      survival. CONCLUSIONS: Overexpression of the p53 and c-erbB-2 proteins indicates
      a high malignant potential in ANN breast cancer, but it is not a significant
      prognostic factor independent of the cell proliferation rate. The correlation
      between overexpression of these proteins and an increased S-phase fraction
      suggests that they may confer a proliferative advantage to cancer cells in vivo.

PMID- 1352360
TI  - Regulation of benzodiazepine prescription.

PMID- 1352361
TI  - Regulation of benzodiazepine prescription.

PMID- 1352362
TI  - Regulation of benzodiazepine prescription.

PMID- 1352363
TI  - Prophylactic intravenous immunoglobulin in HIV-infected children with CD4+ counts
      of 0.20 x 10(9)/L or more. Effect on viral, opportunistic, and bacterial
      infections. The National Institute of Child Health and Human Development
      Intravenous Immunoglobulin Clinical Trial Study Group.
AB  - OBJECTIVE: To evaluate the efficacy of intravenous immunoglobulin (IVIG) for
      prevention of viral, opportunistic, and minor bacterial infections in children
      infected with human immunodeficiency virus (HIV). DESIGN: Randomized, double
      blind, placebo-controlled, outpatient clinical trial comparing subjects treated
      with 400 mg of IVIG per kilogram of body weight every 28 days with those given
      albumin placebo. SETTING: Twenty-eight clinical centers in mainland United States
      and Puerto Rico. PATIENTS: Three hundred seventy-six children infected with human
      immunodeficiency virus with clinical or immunologic evidence of HIV disease, 313
      of whom had entry CD4+ counts of at least 0.20 x 10(9)/L (greater than or equal
      to 200/mm3). MAIN OUTCOME MEASURES: The incidence of laboratory-proven and
      clinically diagnosed viral, opportunistic, and bacterial infections. MAIN
      RESULTS: Viral infections and minor bacterial infections contributed more
      frequently to morbidity in children with entry CD4+ counts of at least 0.20 x
      10(9)/L (together over five times as frequent) than did serious bacterial
      infection, the primary outcome measure of the trial. Opportunistic infections
      occurred at a similar rate as laboratory-proven serious bacterial infections. In
      this group of children, IVIG was significantly associated with a decrease in the
      rate of viral infections and minor bacterial infections per 100 patient-years
      (36.0 vs 54.0 episodes of viral infection per 100 patient-years, IVIG vs placebo,
      P = .01; and 115.1 vs 159.7 episodes of minor bacterial infection per 100 patient
      years, IVIG vs placebo, P = .02), as well as a decrease in the rate of serious
      bacterial infections per 100 patient-years (26.4 vs 48.2 episodes per 100 patient
      years; P = .002). There was no apparent difference in the rate of opportunistic
      infections between treatment arms. CONCLUSIONS: Beneficial effect of IVIG was
      seen across multiple infectious outcome measures, with reductions in serious and
      minor viral and bacterial infections observed in children with entry CD4+ counts
      of at least 0.20 x 10(9)/L.

PMID- 1352364
TI  - [Central autonomic mechanism and neurotransmitters].
AB  - Neurotransmitters involved in the central regulation of the autonomic function
      have, to some extent, been elucidated. Substance P, adrenaline and glutamate
      neurons originating from the rostral ventrolateral medulla oblongata (VLM)
      produce a tonic excitation of sympathetic preganglionic neurons. The A1
      noradrenaline neurons in the caudal VLM inhibit sympathetic activity by
      inhibiting neurons in the rostral VLM. In the dorsal medulla, the baroreceptor
      afferents with substance P converge to the adrenaline-neuropeptide Y (NPY)
      interneurons located in the dorsal strip of the nucleus tractus solitarius (NTS).
      These interneurons suppress neuronal activity of the A2 noradrenaline neurons, a
      vasopressor system, by interacting with alpha 2-adrenergic and NPY receptors. The
      area postrema, a circumventricular organ devoid of the blood-brain barrier, has
      access to regulatory information of blood-borne angiotensin II and atrial
      natriuretic peptide at specific receptors on the neuronal elements. The
      information is then transmitted to the NTS and dorsal motor nucleus of the vagus.
      Studies focusing on the physiological and pharmacological profiles of
      neurotransmitters are expected to enhance our knowledge of the central regulation
      of the autonomic function.

PMID- 1352365
TI  - Pharmacotherapy of schizophrenia in Germany.
AB  - The practice of pharmacotherapy of schizophrenia in Germany is based both on
      clinical experience and research findings. Experience and studies emphasize that
      neuroleptic medication is severely limited by side effects including acute
      extrapyramidal syndromes and tardive dyskinesia. Comparing neuroleptic doses in
      both acute and maintenance therapy have clinicians encouraged to evaluate methods
      for treating patients with the lowest effective dose. Other studies have shown
      that the plasma level may be helpful when deciding which is the best treatment
      for the illness. More precise results for determining the optimum dose of
      antipsychotic compounds in the future may be available from positron emission
      tomography (PET), and from fluorine-magnetic-resonance spectroscopy (FMRS). The
      management of patients whose illness are refractory to conventional neuroleptics
      is also discussed. Benzamides and clozapine, both atypical neuroleptics, may be
      more effective than other available compounds for the severely ill, or for
      patients who are unable to tolerate the neurological side effects of typical
      neuroleptics.

PMID- 1352366
TI  - Surgical alterations of the pancreas and insulin-independent glucose disposal.
AB  - Systemic drainage of pancreatic venous effluent and denervation of the pancreas
      that follows pancreatic transplantation has been shown to alter postoperative
      glucose disposal despite elevated levels of peripheral insulin in response to a
      glucose challenge. Since an appreciable fraction of postprandial glucose disposal
      takes place in the absence of insulin (insulin-independent glucose disposal-
      IIGD), we have investigated potential changes in this aspect of carbohydrate
      metabolism before and after bladder-drained pancreatic auto-transplantation
      (PAT/B) as well as partial pancreatectomy (PPx). The hyperglycemic clamp protocol
      with a background infusion of somatostatin was performed on control (PREOP) dogs
      as well as PAT/B and PPx animals. The rate of glucose disposal (M Value) during
      the period of hypoinsulinemia induced by Somatostatin (SST) was measured and
      reported. Whereas glucose disposal during steady state hyperglycemia was
      significantly diminished for both PPx and PAT/B in the absence of SST, IIGD was
      unaltered across all three groups studied. We therefore conclude that surgical
      alteration of the pancreas results in abnormal glucose disposal during steady
      state hyperglycemia despite apparently normal to supranormal levels of peripheral
      insulin, and that alterations in IIGD are not responsible for these differences.

PMID- 1352367
TI  - Drinking habits and laboratory tests in seamen with and without chemical
      exposure.
AB  - The purpose of this study was to evaluate possible differences in drinking habits
      among seamen exposed to organic solvents and other hydrocarbon compounds compared
      to unexposed seamen. Information about alcohol consumption and alcohol-related
      problems was obtained by using an abbreviated version of the Michigan Alcoholism
      Screening Test, as well as additional questions about the quantity of alcohol
      consumption. Also, tests of serum gamma-glutamyl transferase and mean corpuscular
      volume were performed to reveal possible chronic toxic effects of chemical
      exposure and alcohol consumption, as physicians often use these blood tests in
      their health controls of seamen. The relationships between chemical exposure,
      age, smoking and alcohol consumption and results from blood tests were analyzed
      by using multiple regression analyses. Seamen exposed to organic solvents and
      other hydrocarbon compounds had more alcohol-related problems and more months of
      heavy drinking than did unexposed seamen. The previous year's alcohol consumption
      was similar in the two groups. A relationship between alcohol consumption and
      chemical exposure was not found. No correlation was found between chemical
      exposure and the results from the blood tests. Routine monitoring of gamma
      glutamyl transferase and mean corpuscular volume did not seem useful in the
      evaluation of chemical hazards.

PMID- 1352368
TI  - Long- and short-term survivors after pancreatoduodenectomy for ampullary
      carcinoma.
AB  - Out of 36 consecutive patients who underwent a pancreatoduodenectomy for
      carcinoma of the ampulla of Vater, eight patients (long-term survivors) survived
      more than 5 years after surgery, while eight other patients (short-term
      survivors) survived less than 12 months after intervention. Both the eight long
      term survivors and eight short-term survivors were compared
      clinicopathologically. The long-term survivors did have some preferable factors
      such as a high value of peripheral lymphocytes, a low concentration of
      carcinoembryonic antigen, a small protruding tumor, a shallow depth of invasion,
      a well-differentiated histopathologic type, an infrequent venous invasion, and no
      perineural infiltration. However, these differences were not significant. A
      multivariate regression analysis regarding the 18 prognostic variables showed
      that both perineural invasion and the grade of histopathologic differentiation
      were significant parameters. Out of the eight long-term survivors, three patients
      lived more than 10 years while another died from ampullary carcinoma 74 months
      after surgery. Pancreatoduodenectomy not only produces long-term survivors but
      can also effect a complete cure in patients with ampullary carcinoma. A long
      clinical follow-up of more than 5 years after surgical intervention is thus
      warranted.

PMID- 1352369
TI  - 3H-atipamezole binding sites in mouse cerebral cortex: possible involvement of
      alpha 2-adrenoceptors in sexual behavior.
AB  - Atipamezole is a new specific alpha 2-adrenoceptor antagonist. In this study,
      first, the presence of specific 3H-atipamezole binding sites in the sagittal and
      coronal sections of mouse brain was established using autoradiography. In vitro
      experiments with mouse cerebral cortex membranes indicated that d-medetomidine, a
      new alpha 2-adrenoceptor agonist structurally related to atipamezole, displaces
      labelled atipamezole more potently than noradrenaline. The saturation isotherm
      with d-medetomidine demonstrated high affinity binding with the apparent number
      of binding sites KD 1.36 nM and 760 fmol/mg, respectively. In the next series of
      experiments male mice were sacrificed immediately after copulation and cerebral
      cortex 3H-atipamezole and 3H-flumazenil binding was studied. Oxymetazoline and
      prazosin are known to label preferably alpha 2A and alpha 2B subtypes of alpha 2
      adrenoceptors. Therefore, parallelly with noradrenaline both these compounds were
      used to determine non-specific binding of 3H-atipamezole. When noradrenaline or
      oxymetazoline were used as displacing agents copulation caused a significant
      increase of 3H-atipamezole binding sites. No significant changes were observed
      when prazosin was used. 3H-Flumazenil binding remained unchanged by copulation.
      The up-regulation of 3H-atipamezole binding sites indicates that not only alpha 2
      adrenoceptors in the periphery but also in the CNS may participate in the
      regulation of sexual behavior. Moreover, in regulation of sexual behavior central
      alpha 2-adrenoceptors may be more important than benzodiazepine receptors.

PMID- 1352370
TI  - Best mode of expression of acute reversibility of airway obstruction in patients
      with asthma: application to a new beta-2 agonist, RU 42 173.
AB  - Lung function tests must distinguish a true drug-induced bronchial response from
      changes not related to the drug itself, mainly due to intra-individual
      variability. We compared the variability and ability to detect true drug-induced
      bronchodilation of 3 modes of expression of the increase in forced expiratory
      volume in 1 second (delta FEV1) following administration of a 0.25 mg single oral
      dose of RU 42 173, a new beta 2-agonist. The study was performed in 12 patients
      with reversible obstructive asthma in a double-blind, crossover, placebo
      controlled, randomized manner. The variability of each index was assessed by
      calculating the coefficient of variation (SD/mean). True drug-induced
      bronchodilation was assessed by calculating the F value of each index
      corresponding to the ratio of between-treatment to within-group differences.
      Three modes of expression of delta FEV1 were compared: delta FEV1 (L) = the
      absolute increase in FEV1, delta FEV1 (% baseline) and delta FEV1 (% predicted)
      where delta FEV1 (L) is divided by baseline FEV1 or predicted FEV1, respectively.
      A statistically significant increase in FEV1 was found up to respectively 3, 2
      and 4 hours after dosing when using delta FEV1 (L), delta FEV1 (% baseline) and
      delta FEV1 (% predicted). The highest F value was obtained for delta FEV1 (%
      predicted). The coefficient of variation was lower with delta FEV1 (% predicted)
      than delta FEV1 (L) and delta FEV1 (% baseline). In conclusion, RU 42 173 showed
      a bronchodilating effect which appears to be clinically relevant. delta FEV1 (%
      predicted) was to be the least variable and most powerful index and should be
      preferred to delta FEV1 (L) and even more to delta FEV1 (% baseline) to assess
      the acute airway response to a bronchodilator drug.

PMID- 1352371
TI  - Analysis of the effects of dopamine-1 and dopamine-2 receptor agonists on
      coronary flow.
AB  - The coronary flow (CF) at constant perfusion pressure and other hemodynamic
      variables were measured in anesthetized open-chest dogs. At the same doses of 20,
      100, 500 and 2000 nM, the dopamine-1 receptor agonist, fenoldopam, was much more
      potent than dopamine-2 receptor agonist, N-n-propyl-N-n-butyl dopamine (PBDA), in
      increasing CF. Under conditions of constant systemic arterial pressure,
      fenoldopam produced a dose-related increase in maximal +dp/dt (dp/dt) and CF.
      After adrenergic blockade (combined alpha- and beta-adrenoceptor blockade),
      however, both cardiac and coronary effects of fenoldopam were greatly attenuated.
      The coronary effects of both dopamine agonists under uncontrolled arterial
      pressure were apparently greater than those under constant arterial pressure.
      Under conditions of uncontrolled arterial pressure and after adrenergic blockade,
      fenoldopam induced a dose-related decrease in mean arterial pressure (MAP) and
      corresponding increase in CF. SCH23390 and domperidone markedly inhibited the
      coronary effects of fenoldopam and PBDA, respectively. Our data suggest that the
      coronary effects of fenoldopam are predominantly secondary to the fenoldopam
      induced decrease in total peripheral resistance (TPR) at small doses and to its
      positive inotropic action at large doses, while the primary dopaminergic coronary
      vasodilation plays only a minor role and therefore cannot be of physiological
      importance in regulating CF.

PMID- 1352372
TI  - Chronic colitis associated with human immunodeficiency virus infection.
AB  - OBJECTIVE: A clinical and pathological description of chronic colitis associated
      with human immunodeficiency virus (HIV) infection. DESIGN: A retrospective case
      review. SETTING: Tertiary referral institution and specialist gastroenterology
      practice. PATIENTS: A series of six patients with human immunodeficiency virus
      infection and chronic colitis observed for up to four years. RESULTS: The six
      patients had chronic diarrhoea for longer than six months, rectal bleeding,
      abdominal pain and stool leukocytosis. The mucosal pattern on colonoscopy showed
      diffuse proctocolitis, consisting of contact bleeding, superficial ulcerations,
      exudates, and/or loss of vascular pattern. Colonic biopsies showed a persisting
      diffuse colitis characterised principally by a mixed inflammatory cell infiltrate
      (mononuclear cells and neutrophils) and essentially preserved crypt architecture
      after six to 39 months of histological follow-up. The histopathology over this
      time frame was not typical of ulcerative colitis or Crohn's disease, nor of the
      conventionally described forms of infective colitis. HIV nucleic acid was
      identified by insitu hybridisation in colonic biopsies from four patients. In two
      of three patients tested, the presence of HIV DNA was confirmed by Southern blot
      analysis. No other microbial agent could be demonstrated as the cause of
      diarrhoea. At presentation all patients had CD4+ lymphocyte counts greater than
      265 x 10(6)/L and none had the acquired immunodeficiency syndrome. Four patients
      have gone into remission, the other two patients were not in remission at four
      and a half to five years after onset. CONCLUSION: We suggest that chronic colitis
      may represent a new entity related to infection of the colon with human
      immunodeficiency virus.

PMID- 1352373
TI  - Medicolegal aspects of benzodiazepine dependence. Duties and responsibilities of
      doctors.

PMID- 1352374
TI  - Transcript-specific developmental regulation of polyadenylation in Trypanosoma
      brucei mitochondria.
AB  - Transcripts from many mitochondrial genes in kinetoplastids are heterogeneous in
      size, often occurring as 2 distinct size classes, but this cannot be accounted
      for by RNA editing alone. Analyses of transcripts from 6 mitochondrial genes of
      Trypanosoma brucei indicates that the size variation is due to poly(A) tail
      length. A larger fraction of CYb, COI and COII transcripts have longer poly(A)
      tails in procyclic than in bloodstream forms. These transcripts are also more
      abundant in the procyclic forms. In contrast, a more substantial fraction of CR1
      transcripts have longer poly(A) tails in bloodstream than in procyclic forms and
      these transcripts tend to be more abundant in bloodstream forms. Both ND4 and
      MURF1 transcripts show a similar size distribution of poly(A) tail lengths in
      these life cycle states although both transcripts are more abundant in
      bloodstream forms. Furthermore, genes with edited transcripts tend to have longer
      poly(A) tails than unedited transcripts. Transcript abundance is not strictly
      correlated with longer poly(A) tails. Thus, poly(A) length variation appears to
      be developmentally regulated in a transcript-specific fashion in T. brucei. This
      regulation of polyadenylation may influence mitochondrial gene expression as
      polyadenylation can regulate cytoplasmic gene expression in eukaryotes.

PMID- 1352375
TI  - Beta-adrenergic agonists for preterm labor.

PMID- 1352376
TI  - Beta-agonists and death from asthma.

PMID- 1352377
TI  - Beta-agonists and death from asthma.

PMID- 1352378
TI  - Beta-agonists and death from asthma.

PMID- 1352379
TI  - Beta-agonists and death from asthma.

PMID- 1352380
TI  - Prejunctional muscarine receptors in the rabbit ear artery differ from M1, M2 and
      M3 muscarine receptors.
AB  - The ability of several selective muscarine receptor antagonists to inhibit the
      effect of carbachol on prejunctional muscarine receptors on sympathetic nerve
      endings in the rabbit isolated ear artery was investigated to characterise the
      receptor subtype involved. Carbachol did not reduce responses to exogenous
      noradrenaline and the inhibitory effect of carbachol on responses to nerve
      stimulation was unaffected by hexamethonium (10 microM) indicating that the
      effect of the muscarine agonist was exerted prejunctionally and was not modulated
      by nicotine receptor stimulation. The dissociation constants or apparent
      dissociation constants obtained using (+/-)-benzhexol (pKB; 6.63), (R)-benzhexol
      methiodide (8.11), dicyclomine (5.86), (+/-)-telenzepine (7.34), AF-DX 116
      (6.95), himbacine (7.60), (+/-)-hexahydrosiladiphenidol (5.39) and a
      bisquaternary ammonium compound, heptane-1,7-bis(dimethyl-3'-phthalimidopropyl
      ammonium bromide) (5.84), indicate that the muscarine receptor subtype involved
      is not of the M1, M2 or M3 subtype.

PMID- 1352381
TI  - Effects of the novel dopamine DA2-receptor agonist carmoxirole (EMD 45609) on
      noradrenergic and purinergic neurotransmission in rat isolated kidney.
AB  - The effects of the classical dopamine DA2-receptor agonist quinpirole (LY 171555)
      and the recently characterized DA2-receptor agonist, carmoxirole (EMD 45609), on
      neurotransmission in rat isolated kidney were investigated. After preincubation
      with 3H-noradrenaline, the renal nerves were electrically stimulated. The
      stimulation induced (S-I) outflow of radioactivity was taken as an index of
      noradrenaline release. Quinpirole (0.3 mumol/l) inhibited S-I outflow of
      radioactivity and pressor-responses to renal nerve stimulation (RNS) at 1 Hz.
      Both effects of quinpirole were blocked by the DA2-receptor antagonist S(-)
      sulpiride (10 mumol/l). The alpha 1, alpha 2-adrenoceptor antagonist phentolamine
      (1 mumol/l) did not block the inhibitory effect of quinpirole. Carmoxirole (0.003
      and 0.03 mumol/l) did not alter and carmoxirole (0.3 mumol/l) even enhanced S-I
      outflow of radioactivity, however, pressor responses to RNS were markedly reduced
      by carmoxirole (0.003-0.3 mumol/l). Pressor responses to RNS were also markedly
      reduced by the alpha 1-adrenoceptor antagonist prazosin (0.1 mumol/l).
      Carmoxirole (0.3 mumol/l), prazosin (0.1 mumol/l) and phentolamine (1 mumol/l)
      totally abolished pressor responses to exogenous noradrenaline (0.05 mumol/l). In
      contrast, quinpirole (0.3 mumol/l) did not alter pressor responses to exogenous
      noradrenaline (0.05 mumol/l). Furthermore, carmoxirole (0.003-0.3 mumol/l)
      markedly reduced pressor responses induced by the alpha 1-adrenoceptor agonist
      methoxamine (1 mumol/l) but even the highest concentration of carmoxirole (0.3
      mumol/l) had no effect on pressor responses induced by bolus injections of either
      neuropeptide Y (1.5 ng) or angiotensin II (1 ng). Phentolamine (1 mumol/l) by
      itself markedly enhanced S-I outflow of radioactivity and pressor responses to
      RNS were virtually unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352382
TI  - SK&F 104078, a post-junctionally selective alpha 2-adrenoceptor antagonist in the
      human saphenous vein in vitro.
AB  - The present study investigated the effects of SK&F 104078 (6-chloro-9-[(3-methyl
      2-butenyl)oxy]-3-methyl-1H,2,3,4,- tetrahydro-3-benzazapine) at pre- and post
      junctional alpha 2-adrenoceptors in the human isolated saphenous vein.
      Noradrenaline (0.001-100 mumol/l) produced concentration-dependent contractions
      of the human saphenous vein which were competitively antagonised by the alpha 1
      adrenoceptor antagonist prazosin (0.01-1.0 mumol/l) and the alpha 2-adrenoceptor
      antagonist, rauwolscine (0.01-1.0 mumol/l), indicating the presence of both post
      junctional alpha 1- and alpha 2-adrenoceptors in this preparation. The selective
      alpha 2-adrenoceptor agonist, UK-14,304 (0.01-100 mumol/l) also produced
      concentration-dependent contractions of the human saphenous vein which were
      antagonised by both rauwolscine (0.1 mumol/l) and prazosin (0.1 mumol/l). In the
      presence of angiotensin II (0.05 mumol/l), which itself produced a transient
      contraction, rauwolscine (0.1 mumol/l) produced a rightward shift of the UK
      14,304 concentration-response curve while prazosin (0.1 mumol/l) had no effect.
      SK&F 104078 (10.0 mumol/l) under these conditions also produced a rightward shift
      of the concentration-response curve to UK-14,304, but was at least 100-fold less
      potent than rauwolscine. At pre-junctional alpha 2-adrenoceptors, exogenous
      noradrenaline (0.01 and 0.1 mumol/l) induced a concentration-dependent inhibition
      of stimulation-evoked [7-3H]-noradrenaline release from the human saphenous vein
      in vitro, which was antagonised by rauwolscine (0.1 mumol/l) and tolazoline (10.0
      mumol/l) but not by SK&F 104078 (10.0 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352385
TI  - Histamine H3A receptor-mediated inhibition of noradrenaline release in the mouse
      brain cortex.
AB  - Mouse brain cortex slices preincubated with 3H-noradrenaline were superfused with
      physiological salt solution containing desipramine plus a drug with alpha 2
      adrenoceptor antagonist properties, and the effects of histamine receptor ligands
      on the electrically (0.3 Hz) evoked tritium overflow were studied. The evoked
      overflow (from slices superfused with phentolamine) was inhibited by histamine
      (pIC35 6.53), the H3 receptor agonist R-(-)-alpha-methylhistamine (7.47) and its
      S-(+)-enantiomer (5.82) but not influenced by the H1 receptor agonist 2-(2
      thiazolyl)-ethylamine 3.2 mumol/l and the H2 receptor agonist dimaprit 10
      mumol/l. The inhibitory effect of histamine was not affected by the H1 receptor
      antagonist dimetindene 1 mumol/l and the H2 receptor antagonist ranitidine 10
      mumol/l. The concentration-response curve of histamine (determined in the
      presence of rauwolscine) was shifted to the right by the H3 receptor antagonists
      thioperamide (apparent pA2 8.67), impromidine (7.30) and burimamide (6.82) as
      well as by dimaprit (6.16). The pA2 values of the four drugs were compared with
      their affinities for H3A and H3B binding sites in rat brain membranes (West et
      al. 1990 Mol Pharmacol 38:610); a significant correlation was obtained for the
      H3A, but not for the H3B sites. The results suggest that noradrenaline release in
      the mouse brain cortex is inhibited by histamine via H3A receptors and that
      dimaprit is an H3 receptor antagonist of moderate potency.

PMID- 1352383
TI  - Presynaptic alpha 2-adrenoceptors mediating inhibition of noradrenaline and 5
      hydroxytryptamine release in rat cerebral cortex: further characterization as
      different alpha 2-adrenoceptor subtypes.
AB  - In a previous investigation it was suggested that the alpha 2-adrenoceptors
      regulating 3H-noradrenaline (3H-NA) release and the alpha 2-heteroreceptors
      regulating the release of 3H-5-hydroxytryptamine (3H-5-HT) from rat cerebrocortex
      synaptosomes represent different subtypes of the alpha 2-adrenoceptor in that (-)
      mianserin potently blocked the receptors sited on 5-HT terminals but was
      ineffective at the autoreceptors (Raiteri et al. 1983). In this work a number of
      alpha 2-adrenoceptor antagonists were tested against NA as an inhibitor of the K+
      (15 mmol/l)-evoked release of 3H-NA or 3H-5-HT (in presence of 1 mumol/l
      desipramine or citalopram, respectively) from superfused rat neocortex
      synaptosomes. The order of apparent affinity of the antagonists was: idazoxan
      greater than or equal to ORG 20769 (2-amino-4-(1-methyl-1,2,3,6-tetrahydropyridin
      4-yl)-thiazole-5-ca rbonitrile (Z)-2-butenedioate (1:1) salt) greater than ORG
      20350 (5-chloro-4-(1-butyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2- amine (Z)
      2-butenedioate (1:1) salt) greater than or equal to ORG 20091 (5-chloro-4-(1
      methyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2- amine (Z)-2-butenedioate (2:1)
      salt) at the alpha 2-autoreceptor and idazoxan greater than or equal to ORG 20769
      greater than ORG 20091 much greater than ORG 20350 at the alpha 2-heteroreceptor.
      Prazosin (1 mumol/l) or AR-C 239 (1 mumol/l) (2-[2-[4-(o-methoxyphenyl)piperazine
      1-yl]ethyl]-4,4-dimethyl- 1,3(2H,4H)-isoquinolinedione) were ineffective in both
      systems.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352384
TI  - Withdrawal precipitation by benzodiazepine receptor antagonists in dogs
      chronically treated with diazepam or the novel anxiolytic and anticonvulsant beta
      carboline abecarnil.
AB  - The effects of the benzodiazepine (BZ) receptor antagonists flumazenil (Ro 15
      1788) and the beta-carboline ZK 93426 were compared in dogs before and after
      chronic treatment with diazepam or the novel BZ receptor ligand abecarnil (ZK
      112119). Abecarnil, a beta-carboline, is thought to act as partial (low efficacy)
      and/or subtype selective agonist at central BZ receptors. Diazepam and abecarnil
      were administered at doses which, based on previous experiments on anticonvulsant
      activity, resulted in about equieffective drug concentrations during treatment.
      In dogs treated with diazepam, 6 mg/kg/day p.o., for 2 weeks, severe abstinence
      symptoms, including seizures, were precipitated in all animals by i.v. infusion
      of the BZ receptor antagonists, differences being found in the type of symptoms
      caused by flumazenil and ZK 93426. In dogs treated with abecarnil, 4 mg/kg/d
      s.c., for 6 weeks, only relatively mild abstinence symptoms were precipitated by
      infusion of flumazenil or ZK 93426, although pharmacologically active plasma
      concentrations of abecarnil had been maintained throughout the period of
      treatment. This suggests that BZ receptor ligands which act as partial and/or
      selective agonists might be more favourable than traditional agonists, such as
      diazepam, regarding the induction of physical dependence.

PMID- 1352386
TI  - [Mono-therapy with antihypertensive agents: can a choice be made?].

PMID- 1352387
TI  - Effect of nicotine on extracellular levels of neurotransmitters assessed by
      microdialysis in various brain regions: role of glutamic acid.
AB  - We studied the effect of local administration of nicotine on the release of
      monoamines in striatum, substantia nigra, cerebellum, hippocampus, cortex
      (frontal, cingulate), and pontine nucleus and on the release of glutamic acid in
      striatum of rats in vivo, using microdialysis for nicotine administration and for
      measuring extracellular amine and glutamic acid levels. Following nicotine
      administration the extracellular concentration of dopamine increased in all
      regions except cerebellum; serotonin increased in cingulate and frontal cortex;
      and norepinephrine increased in substantia nigra, cingulate cortex, and pontine
      nucleus. Cotinine, the major nicotine metabolite, had no effect at similar
      concentrations. The cholinergic antagonists mecamylamine and atropine, the
      dopaminergic antagonists haloperidol and sulpiride, and the excitatory amino acid
      antagonist kynurenic acid all inhibited the nicotine-induced increase of
      extracellular dopamine in the striatum. The fact that kynurenic acid almost
      completely prevented the effects of nicotine, and nicotine at this concentration
      produced a 6-fold increase of glutamic acid release, suggests that the effect of
      nicotine is mainly mediated via glutamic acid release.

PMID- 1352388
TI  - Increased plasma glutamic acid in a genetic model of epilepsy.
AB  - A significant increase in the plasma levels of glutamic acid and a significant
      decrease in aspartic acid and taurine in epileptic patients and their first
      degree relatives was reported more than a decade ago and an underlying genetic
      basis for these amino acid changes was suggested. The main objective of the
      present study was to determine the plasma levels of glutamic acid, aspartic acid
      and taurine in El mice which are an inbred epileptic mutant mouse strain. The
      results show a significant increase in plasma glutamic acid but no changes in
      aspartic acid or taurine in the epileptic mice as compared to controls. The data
      provide the first evidence of a significant increase in plasma glutamic acid in
      an animal model of hereditary epilepsy and substantiate the hypothesis that a
      genetic defect underlies the elevated plasma glutamic acid levels in association
      with epilepsy. The findings are also compatible with neurochemical and
      neurophysiological evidence implicating glutamic acid in the mechanism of
      seizures.

PMID- 1352389
TI  - Ultrastructure of neurons containing somatostatin in the dentate hilus of the rat
      hippocampus after cerebral ischaemia, and a note on their commissural
      connections.
AB  - In a light microscopical study, we previously showed that more than 80% of
      somatostatin (SS) immunoreactive (-i) neurons in the hilus of the dorsal part of
      the rat dentate gyrus are lost 4 days after ischemia. In order to verify that the
      loss of SS immunostaining is due to an actual loss of the SS-i neurons and not
      merely a loss in expression of SS immunoreactivity, we have now performed an
      ultrastructural study of these neurons before and 40 h after 20 min of global
      cerebral ischaemia in adult rats. The normal SS-i neurons were multipolar and
      fusiform in shape. The SS-i product was associated with the endoplasmic reticulum
      and occasionally the Golgi apparatus. The cell nuclei had indentations of the
      nucleolemma and contained intranuclear rods. After ischaemia, many SS-i neurons
      in the dentate hilus showed increased electron density of both the cell nucleus
      and the cytoplasm. In addition the cytoplasm was heavily vacuolated with the SS-i
      associated with some of these vacuoles. Other SS-i neurons had, in addition to
      the vacuoles a more homogeneous, and abnormal electron lucent nucleus and
      cytoplasm. These ultrastructural changes correspond to previously reported
      irreversible, ischaemic cell changes of neurons. Based on this we conclude that
      the SS immunoreactivity in the dentate hilus of the dorsal hippocampus is lost
      after ischaemia because of neuronal necrosis. As a minor part of this study, we
      examined whether the ischaemia-susceptible SS-i neurons in dentate hilus had
      commissural axonal projections. This was done utilizing double fluorescence
      microscopy of retrograde axonal transport of the fluorescent dye, Fluoro-Gold,
      and the observation that vulnerable SS-i neurons display homogeneously dispersed
      immunostaining 40 h after ischaemia. Fluoro-Gold was injected unilaterally into
      the dorsal dentate gyrus 5 days prior to ischaemia. Then, 40 h after ischaemia,
      sections were stained for SS immunofluorescence, and examined, in the dentate
      hilus contralateral to the injection, for neuronal co-localization of both
      events. Cell counts revealed double-labelling of 13% of all neurons which
      displayed one of the events. This observation suggests that at least some of the
      ischaemia-susceptible SS-i neurons in dentate hilus do project commissurally. The
      pathophysiological significance of ischaemic loss of commissurally projecting SS
      i neurons in dentate hilus remains to be determined.

PMID- 1352390
TI  - Role of locally produced growth hormone-releasing factor in somatostatin
      regulation by fetal rat brain cells in culture.
AB  - To determine the possible physiological role of endogenous growth hormone
      releasing factor (GRF) in the neuronal content and release of cerebral
      somatostatin (SS), we studied the effect of endogenous GRF blockade on the
      immunoreactive SS (IR-SS) content of cells and media in fetal rat cerebral
      cortical and hypothalamic cells in culture. Cells were cultured in minimum
      essential medium (MEM) with 10% fetal calf serum and 10% horse serum. After 7-10
      days in vitro, media were replaced with MEM without sera containing anti-GRF
      immunoglobulins G (IgG) for 1, 5 or 24 h. Controls were incubated with equal
      amounts of IgG from normal rabbit serum (NRS). In another group of experiments,
      cells were incubated with GRF (10(-11) to 10(-7) M) for 1 or 24 h. Long-term
      exposure (24 h) to anti-GRF IgG resulted in decreased media and intracellular IR
      SS content, in both cerebral cortical and hypothalamic cells. 24 h treatment with
      GRF caused a dose-dependent increase in the IR-SS content of cells and media, the
      stimulatory action being abolished by the addition of anti-GRF to plates
      containing 10(-7) M GRF. On the contrary, when cells were exposed to anti-GRF IgG
      for 1 h, IR-SS increased in the media as compared to the control group. Short
      term incubation (1 h) with GRF (10(-9) to 10(-7) M) resulted in a dose-dependent
      inhibition of IR-SS content in the cells and media. This inhibitory action was
      partially prevented by the addition of anti-GRF to plates containing 10(-7) M
      GRF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352391
TI  - Presence of prion protein in peripheral tissues of Libyan Jews with Creutzfeldt
      Jakob disease.
AB  - The prion protein (PrP) gene on chromosome 20 encodes a protein designated PrPC.
      An abnormal, protease-resistant isoform of PrPC, denoted PrPCJD or PrPSc, is
      present in the brains of patients with Creutzfeldt-Jakob disease (CJD). In Libyan
      Jews, CJD segregates with a point mutation at codon 200 of the PrP gene,
      resulting in the substitution of lysine for glutamate. In the present study, we
      examined the presence of PrP in fibroblasts and leukocytes derived from eight CJD
      patients with the codon 200 mutation. In cultured fibroblasts as well as in
      leukocytes, there was a significant increase in PrP as judged by
      immunocytochemistry in addition to immunoblotting. Most of the PrP in fibroblasts
      and leukocytes could be released from the external surface by
      phosphatidylinositol-specific phospholipase C, a property characteristic of PrPC.
      In leukocytes only, part of the protein was protease resistant, resembling
      PrPCJD. The concentration of PrP mRNA was similar in fibroblast lines derived
      from controls and CJD patients. These results suggest that in CJD patients
      carrying a mutation at codon 200 of the PrP gene, the metabolism of PrP, rather
      than PrP synthesis, is abnormal.

PMID- 1352393
TI  - [Characteristics and clinical use of esmolol].
AB  - Esmolol is a specific beta 1-blocker; it is hydrosoluble, without intrinsic
      sympathetic activity. Distribution half-life is 2 minutes and elimination half
      life 9 minutes. Esmolol is hydrolyzed by the blood esterases. Its indications are
      all those where inotropism and heart rate must be briefly and specifically
      diminished using a titration technique: 1) In patients with coronary artery
      disease, or poor cerebral compliance, just before a strong nociceptive stimulus
      like intubation, extubation, skin incision, etc. 2) In patients with coronary
      artery disease, to decrease oxygen consumption by the myocardium. 3) In patients
      with hypertensive episodes per and post-operatively, especially in vascular
      surgery and neurosurgery. 4) In cardiac insufficiency due to obstructive
      cardiomyopathy. 5) In patients with specific cardiac rhythm problems. 6) In all
      patients where propranolol is indicated bu cannot de administered due to its long
      duration of action. Esmolol has to be given either as a mini-infusion at a rate
      of 300-600 micrograms/kg/min for the first 1-2 minutes followed by 200-300
      micrograms/Kg/min or as a bolus (just before a nociceptive stimulus) 1-3 mg/kg.
      When using esmolol, it is important to set limits within which heart rate and
      blood pressure must remain. Over-dosage can occur easily but can be avoided
      without difficulty.

PMID- 1352392
TI  - [Competitive new generation myorelaxants in pediatric neuroanesthesia].
AB  - Two groups of 50 children were included in a study to examine the use of
      atracurium and vecuronium. In both groups, newborns and infants showed a shorter
      onset time and a longer clinical duration of the first dose of the neuromuscular
      blocking drug. The duration of subsequent doses in the various age groups was not
      significantly different. Atracurium and vecuronium both have a short recovery
      index, good cardiovascular stability and do not interfere with ICP. The Authors
      emphasise the importance of monitoring the use of neuromuscular blocking drugs.

PMID- 1352394
TI  - [New anesthetics and myorelaxants. The behavior of intracranial pressure in
      pediatrics].
AB  - The authors, following a report on cerebral physiology in childhood, report their
      experience of ICP and the administration of new drugs in anaesthesiologic
      practice. The effects of isoflurane, propofol, atracurium, vecuronium on ICP are
      reported.

PMID- 1352395
TI  - [Multiple endocrine neoplasia II A syndrome: relationship between age of the
      patient, levels of basal calcitonin and size of the thyroid tumor].
AB  - This paper presents our experience in four families having the multiple endocrine
      neoplasia (MEN) II-A syndrome, with a total of 19 affected patients. All had
      medullary thyroid carcinoma (MTC), 6 also had pheochromocytoma (PH) and 3 had
      hyperparathyroidism. The screening of the members of the families to measure
      basal and pentagastrin response calcitonin (CT) serum levels allowed an early
      diagnosis of medullary thyroid carcinoma, when lesions were only 1 mm in
      diameter. Measurement of vanillymandelic acid, catecholamines and metanephrines
      in 24-hour urine collections allowed the diagnosis of pheochromocytoma in
      patients, some of whom were asymptomatic. A clear relationship was found between
      the age of the patients, the basal serum calcitonin level and size of the MTC.

PMID- 1352396
TI  - Genomic organization of the putative human homeobox proto-oncogene HOX-11 (TCL-3)
      and its endogenous expression in T cells.
AB  - The HOX-11 (TCL-3) gene, which is abnormally expressed in the leukemic cells of
      some patients with T-cell acute lymphoblastic leukemia, is a new member of the
      homeobox gene family. It is structurally altered by the t(10;14) chromosomal
      translocation, resulting in head-to-tail juxtaposition of HOX-11 with the T-cell
      receptor delta-chain gene. In order to understand the normal functions of HOX-11
      and its role in T-cell leukemia, we have determined the exon-intron structure of
      the HOX-11 gene. By using oligonucleotide primers flanking an intron of the HOX
      11 gene, we have developed a quantitative reverse transcription-polymerase chain
      reaction (RT-PCR) assay for the expression of HOX-11. We detected HOX-11
      expression in multiple cell lineages including normal T cells and two T-cell
      lines in which the HOX-11 gene appeared to be unaltered in structure. Our results
      suggest that deregulation of the endogenous expression of HOX-11 in normal T
      cells represents an essential step towards the formation of this type of T-cell
      leukemia.

PMID- 1352397
TI  - erbB-2 autophosphorylation is required for mitogenic action and high-affinity
      substrate coupling.
AB  - Autophosphorylation of gp185erbB-2 in vivo is confined to its carboxy terminus
      and is required for optimal erbB-2 transforming activity under conditions of
      receptor overexpression. It remains unresolved, however, to what extent
      autophosphorylation regulates erbB-2 mitogenic signaling in normal cells, nor is
      the biochemical basis for such a regulatory function known. To address these
      issues, we utilized a chimeric molecule encompassing the extracellular domain of
      the epidermal growth factor (EGF) receptor (EGFR) fused to the transmembrane and
      intracellular domains of the erbB-2 product. In this EGFR/erbB-2 chimera, erbB-2
      kinase activity is regulated by EGF binding. An EGFR/erbB-2 mutant bearing
      multiple Tyr----Phe substitutions at erbB-2 autophosphorylation sites (EGFR/erbB
      2 5P) displayed markedly reduced phosphotyrosine content following EGF
      stimulation in comparison with the non-mutated chimera. When expressed in NR6
      cells, the EGFR/erbB-2 5P mutant was unable to deliver a sizeable mitogenic
      signal when activated by EGF at physiological levels. In intact cells, the 5P
      mutant was still able to stimulate phosphorylation of the gamma isozyme of
      phospholipase C (PLC-gamma), a prototype erbB-2 substrate, although with a
      delayed time course, indicating that the 5P mutation decreased the affinity of
      the erbB-2 kinase for this substrate. This conclusion was further supported by
      the inability of the 5P mutant to associate with PLC-gamma in co
      immunoprecipitation experiments. We infer that a major role of
      autophosphorylation is to increase the affinity of the erbB-2 kinase for its
      cellular substrates, so that, under physiological conditions, autophosphorylation
      is absolutely required for erbB-2 mitogenic signaling.

PMID- 1352398
TI  - Detection of heterozygous mutations in the RB1 gene in retinoblastoma patients
      using single-strand conformation polymorphism analysis and polymerase chain
      reaction sequencing.
AB  - Several families segregating the autosomal dominant form of the hereditary
      retinoblastoma predisposition gene have been analysed for the causative mutation.
      We have used the single-strand conformation polymorphism (SSCP) technique to
      screen for mutations, exon by exon, in the RB1 gene in affected patients from
      these families. The SSCP technique has proved a rapid and simple technique which
      relies on the sequence-dependent migration of single-stranded DNA in a non
      denaturing polyacrylamide gel. Oligonucleotide primers flanking all 27 exons and
      the promoter region of the RB1 gene are reported here. The polymerase chain
      reaction (PCR)-amplified products range in size from 212 to 625 bp and include a
      flanking intron sequence which allows detection of mutations in these regions.
      The sensitivity of SSCP is optimal when DNA fragments are approximately 200 bp
      long. Consequently, restriction enzyme sites for each amplified region were
      identified, reducing the size of the PCR products analysed to less than 250 bp.
      Bands with aberrant migration patterns were observed on SSCP gels in the
      lymphocyte DNA from two patients with bilateral, familial retinoblastoma.
      Sequence analysis of these DNA fragments revealed the causative mutations. These
      consisted of a 1-bp insertion of a T in the coding strand of exon 20 and a G----A
      mutation in the coding strand of exon 14. This approach has proved to be a
      powerful method for the rapid detection of germline mutations in the RB1 gene, a
      programme which can be extended to individuals with new mutations.

PMID- 1352399
TI  - Tetraethylammonium blocks muscarinically evoked secretion in the sheep parotid
      gland by a mechanism additional to its blockade of BK channels.
AB  - Since the secretory cells of the sheep parotid gland contain large numbers of
      high-conductance, voltage- and Ca(2+)-activated K+ channels (BK channels), we
      have used tetraethylammonium (TEA), a commonly employed blocker of BK channels,
      to investigate their role in secretion by this gland. In patch-clamp studies we
      found that 10 mmol/l TEA applied extracellularly inhibits the BK channel but not
      a 30-pS K+ channel also seen in this gland. We then showed by in-vivo perfusion
      that muscarinically evoked secretion is inhibited almost completely by 10 mmol/l
      TEA. We next used microspectrofluorimetry with fura-2 to demonstrate that
      muscarinic agonists cause the intracellular free Ca2+ concentration to increase.
      Unexpectedly, however, we found that 0.3-10 mmol/l TEA inhibited the increase in
      intracellular free Ca2+ induced by 5.0 mumol/l bethanechol or by 0.1 mumol/l
      acetylcholine. Consequently we conclude that the inhibition of muscarinically
      evoked secretion by the sheep parotid gland by TEA cannot be attributed solely to
      blockade of the BK channel--rather it must be attributed, at least in part, to
      blockade of some step in muscarinic signal transduction, for instance, receptor
      agonist binding or Ca2+ release into the cytosol.

PMID- 1352401
TI  - Distribution of FMRFamide-like immunoreactivity in the forebrain of the catfish,
      Clarias batrachus (Linn.).
AB  - The anatomical distribution of FMRFamide-like immunoreactivity in the forebrain
      and pituitary of the catfish, Clarias batrachus, was investigated. Immunoreactive
      cells were observed in the ganglion cells of the nervus terminalis (NT) and in
      the medial olfactory tracts. In the preoptic area, FMRFamide-containing perikarya
      were restricted to the lateral preoptic area, paraventricular subdivision of the
      nucleus preopticus, nucleus suprachiasmaticus and nucleus preopticus
      periventricularis posterior. In the postoptic area, some cells of the nucleus
      postopticus lateralis and nucleus of the horizontal commissure showed moderate
      immunoreactivity. In the tuberal area, immunoreactivity was observed in few cells
      of the nucleus hypothalamicus ventralis and nucleus arcuatus hypothalamicus
      (NAH). Nucleus ventromedialis thalami was the only thalamic nucleus with
      FMRFamide immunoreactivity. Immunoreactive processes were traceable from the NT
      through the medial as well as lateral olfactory tracts into the telencephalon and
      the area ventralis telencephali pars supracommissuralis (Vs). Further caudally,
      the immunoreactive fibers could be traced into discrete areas, including
      habenular and posterior commissures, neurohypophysis and pituitary; isolated
      fibers were also observed in the pineal stalk. A loose network of immunoreactive
      processes was observed in the olfactory bulbs and the entire telencephalon, with
      higher densities in some areas, including Vs. A dense plexus of immunoreactive
      fibers was seen in the pre- and postoptic areas and around the paraventricular
      organ, while relatively few were observed in the thalamus. A high concentration
      of fiber terminals was found in the caudal tuberal area.

PMID- 1352402
TI  - VI International Conference on Early Prenatal Diagnosis of Genetic Diseases "From
      Gametes to Embryo". Milan, May 18-20, 1992. Abstracts.

PMID- 1352403
TI  - Relevance of animal studies to the evaluation of human cancer risk. Proceedings
      of a symposium. Austin, Texas, December 5-8, 1990.

PMID- 1352400
TI  - Identification of a homeobox-containing gene located between lin-45 and unc-24 on
      chromosome IV in the nematode Caenorhabditis elegans.
AB  - Using two primers corresponding to helix 1 and helix 3 regions in the
      homeodomain, we subjected genomic DNA from Caenorhabditis elegans to
      amplification by the polymerase chain reaction. Sequence analysis of the
      amplified products revealed a new homeobox-containing gene, designated ceh-19.
      This gene was located between lin-45 and unc-24 on chromosome IV where no
      homeogene has previously been mapped.

PMID- 1352404
TI  - Age-related changes in opioid peptide concentrations in brain and pituitary of
      spontaneously hypertensive rats. Effect of antihypertensive drugs and comparison
      with deoxycorticosterone acetate and salt hypertension.
AB  - The relationship of age-dependent changes in concentrations of various opioid
      peptides in the brain and pituitary to the development of hypertension was
      studied in the spontaneously hypertensive rat (SHR). Normotensive Wistar-Kyoto
      (WKY) and Sprague-Dawley rats served as controls. Opioids determined were
      dynorphin A (1-8) [DN-A(1-8)], beta-endorphin (BE) and Met-enkephalin (ME). Three
      approaches were used: (1) temporal correlations of opioid concentrations with the
      onset of hypertension in 4-, 8-, 12- and 16-week-old rats; (2) study of opioid
      changes when hypertension development was prevented with antihypertensive drugs
      and (3) determination of possible opioid peptide changes in another rat model of
      hypertension, the deoxycorticosterone acetate (DOCA) + salt model. Opioid peptide
      concentration differences (SHR/WKY) found were as follows. There were much lower
      DN-A(1-8) levels in the SHR hippocampus and hypothalamus at all ages studied. At
      12 and 16 weeks, coincidently with the onset of hypertension, lower levels of BE
      were found in the anterior lobe of the pituitary, but there were higher BE and ME
      levels found in the neurointermediate lobe (NIL). Prevention of hypertension in
      SHR by 8 weeks of oral therapy with guanethidine and hydralazine reversed the BE
      and ME changes in the NIL but not in the anterior lobe. There were no brain or
      pituitary changes in opioid peptide concentrations associated with DOCA-salt
      hypertension. The results are interpreted as supporting a role for altered
      concentrations of brain and pituitary opioids in the genesis of SHR hypertension.

PMID- 1352406
TI  - Physician's assistants in vascular and interventional radiology.

PMID- 1352405
TI  - Effects of anoxia on the biphasic response of isolated strips of rabbit bladder
      to field stimulation, bethanechol, methoxamine and KCl.
AB  - The contractile response of the bladder can be divided into two phases: an
      initial rapid increase in tension and a prolonged period of sustained tension
      (plateau phase). The bladder empties primarily during the plateau phase of the
      contractile response. These two phases can be differentiated using both
      pharmacologic and metabolic agents, indicating that the two phases have
      independent energy requirements. The present study compares the phasic (peak) and
      tonic (plateau) components of the responses of isolated strips of bladder body
      and base to field stimulation, bethanechol, methoxamine and KCl administration.
      New Zealand White rabbits were anesthetized with pentobarbital, and the bladder
      was removed. The bladder was divided between body and base at the level of the
      ureteral orifices. Three strips of bladder body and three strips of bladder base
      were mounted in separate baths containing Tyrode's solution at 37 degrees C and
      equilibrated with 95% O2, 5% CO2. Anoxia was produced by changing the gas mixture
      to 95% nitrogen, 5% CO2. The effects of anoxia on the responses to field
      stimulation, bethanechol, methoxamine and KCl were determined at different times
      after the initiation of anoxia. The results of these studies can be summarized as
      follows: (1) Anoxia induced time-dependent plateau phases of the response to
      field stimulation (2 and 32 Hz). (2) The rate of inhibition of the plateau phase
      was significantly and substantially greater than that of the peak phase in both
      the bladder body and base. (3) Similarly, anoxia inhibited the plateau phase of
      the bladder body's response to bethanechol to a significantly and substantially
      greater degree than anoxia inhibited the peak contraction.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1352407
TI  - [Treatment with somatostatin of pancreatic ascites].
AB  - Pancreatic ascites is an entity defined as amylase levels up to 1.000 U/l in
      ascitic liquid. Frequently, it is secondary to a rupture of pancreatic ductus or
      pseudocyst and foreward communication to peritoneal space. We present a male
      diagnosed of calcified alcoholic chronic pancreatitis with pancreatic ascites
      secondary to a pseudocyst. Combination of parenteral nutrition and sintetic
      cyclic somatostatin was efficient. It would act by reducing pancreatic secretion
      in a long-term manner, which is the final purpose of the treatment. This
      association would be considered as a former tool in ascitic pancreatic patients,
      evacuatory punction or delayed surgery been relegated to a conservatory treatment
      failure or when primary pathology indicate it.

PMID- 1352408
TI  - Humoral responses to a multivalent vaccine in age-matched lambs of different
      bodyweight and nutrition.
AB  - K-agglutination, pilus-enzyme-linked immunosorbent assay (ELISA) and outer
      membrane protein-ELISAs were used to assess humoral responses after vaccination
      with a commercial, multivalent, ovine foot rot vaccine (Dichelobacter nodosus
      whole cells) in three groups of nine-month-old lambs of markedly different
      bodyweight, nutritional history and dietary protein supply. Mean bodyweights of
      lambs in low (L), medium (M) and high (H) bodyweight/nutrition groups were 22, 32
      and 48 kg, respectively, at the time of vaccination. Few significant differences
      in humoral responses to vaccine antigens were found between groups. However,
      lambs in group H tended to have lower levels of antibody to a greater number of
      component antigens than did lambs in the other groups. These results suggest that
      low bodyweight due to poor nutrition is unlikely to affect the response of sheep
      to multivalent foot rot vaccines.

PMID- 1352410
TI  - [A long-term result of coronary artery bypass on left coronary ostial stenosis
      secondary to Takayasu's disease: a case report].
AB  - A 37-year-old woman was admitted to our hospital for post operative coronary
      angiography. At the age of 17, she was diagnosed as having Takayasu's disease and
      at that time prednisolone was administered. At the age of 22, she was operated on
      to receive a coronary artery bypass graft (CABG) because of a 95% isolated
      stenosis in the left coronary ostium. Pathological specimen obtained from the
      ascending aorta demonstrated a proliferative stage of Takayasu's aortitis. After
      the CABG, she married and delivered two children, with the inflammation being
      kept under control by prednisolone. Coronary angiography performed 13 years after
      the operation proved the saphenous vein graft to the left anterior descending
      artery to be still patent. To our knowledge, this case has the longest history of
      a patent CABG used in an operation to correct the ostial stenosis secondary to
      Takayasu's disease. According to the previous reports we collected, the long-term
      patency rate of CABG is 78%, whereas that of ostial endarterectomy is unknown.
      Whether CABG or endarterectomy is better as an operating method for ostial
      stenosis due to aortitis is still a controversial point. We hope that reports of
      further examples will be available in order to help make the final decision.

PMID- 1352409
TI  - Loss of absorptive capacity for sodium and chloride in the colon causes diarrhoea
      in Potomac horse fever.
AB  - Ehrlichia risticii, an obligate intracellular bacterium in the family
      Rickettsiaceae, causes Potomac horse fever which is often associated with severe
      watery diarrhoea. The mechanism of the diarrhoea is unknown. The aim of this
      study was to determine whether sodium and chloride transport, morphology and
      cyclic adenosine 3', 5'-monophosphate (cyclic AMP) content of colonic mucosa was
      altered in E risticii-infected horses. Mucosa-submucosa sheets from the large and
      small colon of nine infected and seven to nine uninfected horses were set up in
      Ussing chambers for measurement of short-circuit current and transepithelial 22Na
      and 36Cl fluxes. Uninfected tissues absorbed both sodium and chloride whereas
      absorption of sodium and chloride was abolished in infected tissues. Bethanechol
      and histamine evoked a concentration-dependent increase in short-circuit current
      in both groups, but the responses were attenuated at all concentrations in
      infected horses. Slight focal degeneration of colonic epithelial cells and loss
      of microvilli from glandular epithelial cells occurred in infected horses. There
      was a significant increase in cyclic AMP content in colonic mucosa of infected
      animals. The results suggest that E risticii infection induces focal microscopic
      degeneration of epithelial cells and an increase in intracellular cyclic AMP in
      colonic mucosa. These alterations are associated with malabsorption of sodium and
      chloride and could cause diarrhoea.

PMID- 1352412
TI  - Evolution of HIV in Africa.

PMID- 1352411
TI  - [Severe diarrhea in AIDS treated with a somatostatin analog. Report of a case].
AB  - We herein report a 30 years old male patient with AIDS and Cryptosporidium
      diarrhea diagnosed by intestinal biopsy. After some days of unsuccessful
      conventional anti-diarrheal treatment, an analog of somatostatin (octreotide
      acetate) Sandostatin was started. The stool volume and the bowel movements
      decreased dramatically and in spite of some collateral effects the patient could
      be clinically improved and discharged from the hospital.

PMID- 1352413
TI  - Mosquito molecular genetics: the hands that feed bite back.

PMID- 1352414
TI  - Selection of drug-resistant bone marrow cells in vivo after retroviral transfer
      of human MDR1.
AB  - Experiments were performed to determine if retroviral-mediated transfer of the
      human multidrug resistance 1 gene (MDR1) into murine bone marrow cells would
      confer drug resistance to the cells and whether the MDR1 gene could be used as a
      dominant selectable marker in vivo. When mice transplanted with bone marrow cells
      containing a transferred MDR1 gene were treated with the cytotoxic drug taxol, a
      substantial enrichment for transduced bone marrow cells was observed. This
      demonstration of positive selection establishes the ability to amplify clones of
      transduced hematopoietic cells in vivo and suggests possible applications in
      human therapy.

PMID- 1352415
TI  - Second primary lesions in the biliary tree after successful resection of
      ampullary carcinoma.
AB  - Two patients are described who had an adenocarcinoma at the site of the
      hepaticojejunostomy 5 and 15 years after pancreaticoduodenectomy for an ampullary
      adenocarcinoma. Both patients had symptoms and signs of biliary obstruction. Both
      tumors were identified by upper endoscopy and resected at laparotomy. In both
      patients the tumor was considered a new primary carcinoma rather than a recurrent
      or metastatic carcinoma. Evidence to support this was the finding of an
      intraepithelial component of the tumor in the resection specimens of both
      patients, the fact that the tumors were on the luminal side of the distal bile
      duct in both cases, lack of other evidence of recurrent or metastatic tumor, and
      the time interval between the pancreaticoduodenectomy and the development of the
      new tumor.

PMID- 1352416
TI  - [Increased liver enzymes: what should be done?].
AB  - The transaminases, alkaline phosphatase (AP) and gamma-glutamyl transferase (G
      GT) are most widely used as indicators of hepatobiliary disease. Elevated serum
      levels of transaminases (AST and ALT) usually indicate hepatocellular damage. ALT
      elevations, however, can also be of extrahepatic origin (muscle). The ratio of
      the transaminases in serum (AST/ALT) and the mitochondrial isoenzyme of AST are
      frequently higher in alcoholic than in non-alcoholic liver diseases. Serum
      activities of AP and G-GT are elevated in cholestasis: Both enzymes, however, are
      not liver-specific and G-GT activity is induced by alcohol and certain drugs. A
      hepatic enzyme pattern (predominant transaminase elevation) should be
      discriminated from a cholestatic pattern (predominant AP and G-GT elevation). The
      most frequent diagnoses in asymptomatic patients with accidentally detected,
      mostly mild to moderate transaminase elevations are: alcoholic liver disease,
      (mostly chronic) viral hepatitis, and already much less frequently, drug induced
      liver disease and non-alcoholic steatosis. Solely if the respective
      investigations are negative or/and the transaminases stay elevated for greater
      than or equal to 6 months despite strict alcohol abstinence, omission of any
      potentially hepatotoxic drug or weight reduction are further steps justified.

PMID- 1352418
TI  - Abstracts of the 6th International Congress of Toxicology. Rome, 28 June-3 July
      1992.

PMID- 1352417
TI  - Registry of DNA polymorphisms within or close to the human factor VIII and factor
      IX genes. For the Factor VIII/IX Subcommittee of the Scientific and
      Standardization Committee of the International Society on Thrombosis and
      Haemostasis.

PMID- 1352419
TI  - Cryptorchidism in newborns with gastroschisis and omphalocele.
AB  - A retrospective study was undertaken to determine if there exists an association
      between cryptorchidism and the intra-abdominal wall defects of gastroschisis and
      omphalocele. The records of 25 newborn male infants (13 with omphalocele, 12 with
      gastroschisis) were examined. In this sample there was no statistically
      significant association between these defects and cryptorchidism in either the
      premature or the full-term infants, when compared with a healthy population.
      Further clinical studies with larger numbers of patients are recommended.

PMID- 1352420
TI  - [Differentiation of fetal lymphocytes with the DP-(dipeptidylpeptidase-) IV
      technique].
AB  - The knowledge about the ontogenicity of the human immune system based on animal
      experiments. In this study expulsed fetus of women with sponeous and arteficial
      abortions were analysed because of the content of T4(+)-lymphocytes in the
      lymphatic tissues. The thymus, spleen, and a piece of the bone marrow were
      dissected, homogenised and the lymphocytes were separated. The identification of
      the T4+ cells was performed by the cytochemical staining of dideptidyl peptidase
      IV (DP IV). It could established that from the 15th to the 26th week of gestation
      the number of T4+ cells increased in the thymus and spleen but not in the bone
      marrow. In cases with rubella infection was the number of T4+ cells in the spleen
      increased if the fetus have had no signs of embryopathy.

PMID- 1352421
TI  - Intrinsic and drug-induced seizures of adult and developing gerbils.
AB  - Seizures elicited by posture change and intraperitoneal administration of
      convulsants were studied ontogenetically in the Mongolian gerbil (Meriones
      unguiculatus). In posture change, the first signs of seizure appeared after age 6
      weeks with maximal frequency at 8-9 weeks. Adults developed complex, but
      stereotyped, seizures. Facial twitch was followed by the generalized convulsion,
      further progressing to trembling of the limbs and then kicking of the hindlimb
      (full seizure) after 55 days of age. Pentylenetetrazole induced a seizure similar
      to the full event in gerbils as young as 37 days of age. The seizure pattern
      elicited by strychnine or glutamate was different from that of
      pentylenetetrazole.

PMID- 1352422
TI  - [Effects of alpha 2-agonist apraclonidine on norepinephrine levels in the rat
      iris-ciliary body].
AB  - In an attempt to estimate the in vivo catecholamine level in rat iris-ciliary
      body, animals were sacrificed by microwave irradiation which rapidly inactivates
      metabolic enzymes. Catecholamine levels in the iris-ciliary body were determined
      by high-performance liquid chromatography with electrochemical detection. The
      norepinephrine level in rat iris-ciliary body per gram tissue protein was 3.56 +/
      0.22 micrograms/g (21.1 +/- 1.3 nmol/g)(mean +/- SEM, n = 7). Neither dopamine
      nor epinephrine were detected. A single instillation of 5 microliters of an 0.05%
      apraclonidine (alpha 2-agonist) to one eye of a rat increased the norepinephrine
      level in the iris-ciliary body by 7.7% one hour after administration (p less than
      0.05).

PMID- 1352423
TI  - Acute pain management in adults: operative procedures. Agency for Health Care
      Policy and Research.

PMID- 1352424
TI  - Turbidimetric assessment of the compatibility of taxol with selected other drugs
      during simulated Y-site injection.
AB  - The compatibility of taxol in 5% dextrose injection with each of 17 other drugs
      during simulated Y-site injection was studied through visual and turbidimetric
      assessment. A 4-mL sample of taxol 1.2 mg/mL in 5% dextrose injection was
      combined with a 4-mL sample of each of 17 drugs at concentrations that are used
      clinically. Each combination was prepared in duplicate, with the order of mixing
      reversed between the two samples. The samples were inspected visually in normal
      fluorescent light, in high-intensity light, and against light and dark
      backgrounds with a 3-diopter magnification lens initially and at 30 minutes, one
      hour, and four hours. A turbidimeter was used to measure the turbidity of each
      drug combination in triplicate initially and at one and four hours after mixing.
      None of the drug combinations resulted in visual evidence of precipitation, color
      change, or gas production, and the turbidity was essentially unchanged over the
      four-hour observation period. Taxol 1.2 mg/mL in 5% dextrose injection exhibited
      no visual or turbidimetric evidence of incompatibility when combined with each of
      17 other drugs during simulated Y-site injection. However, drug combinations for
      which no visual or turbidimetric incompatibility is apparent may not be
      chemically stable; therefore, practitioners should be cautious in applying these
      findings to the clinical setting.

PMID- 1352425
TI  - Advances in outpatient antimicrobial therapy: loracarbef.

PMID- 1352426
TI  - Inflammation and airway reactivity in asthma.
AB  - The increased airway reactivity characteristic of asthma may be due to
      contraction of airway smooth muscle, mucus hypersecretion, edema and thickening
      of airway walls, and the presence of serum proteins and inflammatory cells and
      their products in the airways. Increased airway reactivity in asthma correlates
      with airway epithelial damage and is clearly related to airway inflammation, a
      process that most likely involves a complex interaction among mast cells,
      lymphocytes, eosinophils, and macrophages. Thus, although symptomatic treatment
      of airway narrowing is best accomplished with bronchial smooth muscle relaxants,
      treatment of the basic pathophysiologic defect should attempt to reduce airway
      inflammation. Bronchodilators (inhaled beta-agonists and, occasionally,
      theophylline), which do not decrease airway reactivity, are often used to treat
      the symptoms of patients with mild or episodic asthma; inhaled corticosteroids,
      which do decrease airway inflammation and reactivity, are used to treat patients
      with more severe symptoms. Methotrexate and cromolyn sodium may also be used,
      although their role in treating the underlying pathophysiology remains
      controversial. Identification of new agents that are as effective as
      corticosteroids but that do not produce their side effects would represent a
      major therapeutic advance for patients with asthma.

PMID- 1352427
TI  - Bilateral anophthalmia, esophageal atresia, and right cryptorchidism: a new
      entity?
AB  - We report on a child with bilateral anophthalmia, esophageal atresia, and
      cryptorchidism. This is the first case observed in the Spanish Collaborative
      Study of Congenital Malformations (ECEMC) with this constellation of congenital
      anomalies, and it is similar to that described in 1988 by Rogers. We think that
      it may constitute a new syndrome.

PMID- 1352428
TI  - Apraclonidine and argon laser trabeculoplasty.
AB  - Sixty patients with medically uncontrolled open-angle glaucoma (intraocular
      pressure greater than 21 mm Hg) were randomly assigned to one of two treatment
      regimens with apraclonidine before undergoing 360-degree argon laser
      trabeculoplasty. One drop of apraclonidine 1% was instilled one hour before and
      immediately after laser treatment in 30 eyes or apraclonidine was delivered only
      after trabeculoplasty in 30 eyes. Intraocular pressure before laser treatment,
      number of antiglaucoma medications, and the laser treatment settings were
      comparable between the two groups. The mean and percent change in intraocular
      pressures were similar in both treatment groups one and two hours after
      trabeculoplasty. One drop of apraclonidine 1% instilled immediately after argon
      laser trabeculoplasty prevented intraocular pressure increase one hour and two
      hours postoperatively as effectively as its instillation both one hour before and
      immediately after laser treatment.

PMID- 1352429
TI  - Dopamine DA1 receptor agonist, fenoldopam, reverses glycine-induced
      hyperfiltration in rats.
AB  - Stimulation of dopamine DA1 receptors can prevent glomerular hyperfiltration in
      streptozotocin-induced diabetic rats. In the present study we have therefore
      investigated whether the DA1 agonist, fenoldopam, can prevent glycine-induced
      hyperfiltration. Glomerular filtration rate (GFR) and effective renal plasma flow
      (ERPF) were measured by inulin and p-aminohippurate clearances in conscious
      chronically instrumented rats. Glycine (3.7 mg/min iv; n = 8) significantly
      increased GFR by 37% (from 1.09 +/- 0.53 to 1.49 +/- 0.11 ml.100 g-1.min-1, P
      less than 0.01), ERPF by 23% (from 2.96 +/- 0.30 to 3.64 +/- 0.43 ml.100 g-1.min
      1, P less than 0.05), and filtration fraction (FF) by 13% (from 0.39 +/- 0.04 to
      0.44 +/- 0.05, P less than 0.05). Fenoldopam, at a dose (1 microgram.kg-1.min-1
      iv; n = 8) that increased ERPF by 26%, decreased FF by 13%, but did not change
      GFR, significantly attenuated the glycine-induced hyperfiltration. In the
      presence of fenoldopam, glycine resulted in only an 8% increase in GFR (from 1.08
      +/- 0.07 to 1.17 +/- 0.09 ml.100 g-1.min-1; n = 8). ERPF increased by 20% (from
      3.34 +/- 0.24 to 4.00 +/- 0.21 ml.100 g-1.min-1, P less than 0.05), and FF
      decreased by 13% (from 0.34 +/- 0.03 to 0.29 +/- 0.02, P less than 0.05).
      Infusion of the DA1-selective antagonist, Sch 23390, abolished the effects of
      fenoldopam. Thus DA1 receptor activation can prevent glomerular hyperfiltration
      induced by glycine.

PMID- 1352430
TI  - Intrarenal DA2 dopamine receptor stimulation in the conscious dog.
AB  - DA2 dopamine receptors are present in renal blood vessels and glomeruli.
      Stimulation of DA1 dopamine receptors leads to renal vasodilation, diuresis, and
      natriuresis, but a functional role for renal DA2 receptors is largely unknown. We
      investigated the possible role of DA2 receptors in the control of renal function
      by intrarenal infusion of a highly specific DA2 agonist, LY 171555 (LY), in
      conscious uninephrectomized dogs (n = 5) in metabolic balance at sodium intake of
      40 meq/day. The infusion of LY at 0.5 pmol.kg-1.min-1 did not change the urinary
      sodium excretion or renal hemodynamic function. A significant dose-dependent
      antidiuresis (F = 8.1, P less than 0.0001) and antinatriuresis (F = 93.3, P less
      than 0.0001) and a decrease in filtration fraction (F = 2.3, P less than 0.02)
      occurred as the LY dose was increased from 1.0 to 10.0 pmol.kg-1.min-1. There
      were no changes in systemic plasma renin activity, plasma aldosterone
      concentration, or mean arterial pressure during intrarenal LY administration.
      These data suggest that intrarenal DA2 receptor stimulation with LY decreases
      renal sodium excretion in part by hemodynamic mechanisms. Renal dopamine may act
      at vascular and/or glomerular DA2 receptors to modulate renal function.

PMID- 1352431
TI  - Hypercapnic blood flow reactivity not increased by alpha-blockade or cordotomy in
      piglets.
AB  - We tested the hypothesis that differential sympathetic innervation explains the
      attenuated cerebral blood flow (CBF) response to hypercapnia (hyper) in fore
      brain (fb) compared with brain stem in 1- to 2-wk-old piglets. In pentobarbital
      sodium-anesthetized piglets, CBF (microspheres) was measured during hypocapnia,
      normocapnia (normo), and hypercapnia [arterial CO2 partial pressure (PaCO2) of
      25, 40, and 65 mmHg, respectively] in random sequence. After pretreatment values
      were obtained, piglets were randomized to undergo sham treatment (n = 5), high
      cervical spinal cord transection (n = 6), or pharmacological alpha-adrenergic
      blockade (prazosin 1 mg/kg + yohimbine 1 mg/kg, n = 6). After each experimental
      treatment, CO2 reactivity was again measured. Before experimental manipulation,
      hypercapnic reactivity [(CBFhyper - CBFnormo)/(PaCO2hyper - PaCO2normo)] in brain
      stem was approximately three times greater than in forebrain (e.g., sham; 3.6 +/-
      0.8 vs. 1.2 +/- 0.3 ml.min-1.100 g-1.mmHg-1). Hypercapnic reactivity in forebrain
      was not increased by cord transection (1.4 +/- 0.3 vs. 1.1 +/- 0.2 ml.min-1.100 g
      1.mmHg-1) or alpha-blockade (1.6 +/- 0.6 vs. 1.2 +/- 0.4 ml.min-1.100 g-1.mmHg
      1). Likewise, hypercapnic cerebral vascular resistance (CVR) was unchanged by
      experimental treatment (e.g., CVRfb; cord transection 1.1 +/- 0.1 vs. 1.0 +/-
      0.1; alpha-blockade 1.1 +/- 0.2 vs. 1.0 +/- 0.1 mmHg.ml-1.min-1.100 g-1).
      Hypocapnic vasoconstriction, however, was attenuated by both cord transection and
      alpha-blockade in forebrain and brain stem. We conclude that physiological
      stimulation of the noradrenergic component of the sympathetic nervous system does
      not explain regional differences in CBF reactivity during hypercapnia in 1- to 2
      wk-old piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352432
TI  - Anoxia/reoxygenation-induced neutrophil adherence to cultured endothelial cells.
AB  - Previous studies have shown enhanced neutrophil adhesion to endothelial cells
      exposed to anoxia and then reoxygenated (A/R). To define the molecular basis for
      these observations, we evaluated the relative roles of CD11/CD18 determinants
      (CD11a and CD11b) of neurtrophils and the endothelial adhesion proteins
      intercellular adhesion molecule 1 (ICAM-1) and endothelial-leukocyte adhesion
      molecule 1 (ELAM-1). Human umbilical vein endothelial cell (HUVEC) monolayers
      were exposed to anoxia for 30 min, reoxygenated, and then reacted with 51Cr
      labeled neutrophils in adhesion assays. Neutrophil adhesion to HUVEC exposed to
      A/R was significantly increased (2.7-fold) as compared with that observed with
      normoxic (control) HUVEC. This A/R-induced hyperadherence was significantly
      diminished by monoclonal antibodies (MAb) directed at CD11a, CD11b, CD18 or ICAM
      1, but not by MAb directed at ELAM-1. The inhibitory effects of anti-CD11a and
      anti-CD11b were additive and equivalent to that of anti-CD18 MAb. A/R did not
      elicit increased levels of ICAM-1 or ELAM-1 mRNA or surface protein. However,
      immunofluorescence flow cytometry indicated that incubation of neutrophils in
      supernatants of A/R-conditioned HUVEC elicited an increase of surface CD11b and
      CD18, but not CD11a. Supernatants from A/R-conditioned HUVEC promoted neutrophil
      adherence to naive HUVEC, and this hyperadhesivity was diminished by a platelet
      activating factor (PAF) receptor antagonist and catalase but not by a 5
      lipoxygenase inhibitor, a leukotriene B4 receptor antagonist, or superoxide
      dismutase. These studies indicate that A/R promotes neutrophil adherence via
      CD11a/CD18- and CD11b/CD18-dependent interactions with ICAM-1 that appear to be
      mediated by hydrogen peroxide and PAF.

PMID- 1352433
TI  - Medullary pathways for adrenocorticotropic hormone and vasopressin secretion in
      rabbits.
AB  - We determined, in urethan-anesthetized rabbits, whether pharmacological
      alteration of neuronal function in the ventrolateral medulla oblongata, including
      the A1 area, and in the nucleus tractus solitarii (NTS), alters plasma
      adrenocorticotropic hormone (ACTH) and vasopressin and whether inhibition of
      neuronal function in the ventrolateral medulla impairs the secretion of ACTH
      normally observed in response to hemorrhage or constriction of the inferior vena
      cava. We also tested whether the increase in plasma ACTH and vasopressin after
      pharmacological inhibition of neuronal function in the NTS is dependent on a
      pathway that synapses in the A1 area of the ventrolateral medulla. Activation of
      the A1 area with bicuculline increased both ACTH and vasopressin. Inhibition of
      the NTS with muscimol increased levels of both hormones, as did hemorrhage and
      constriction of the inferior vena cava. Inhibition of neuronal function within
      the A1 area with muscimol eliminated the secretion of vasopressin but did not
      significantly alter the secretion of ACTH, obtained by injecting muscimol into
      the NTS. Injection of muscimol into the A1 area eliminated the secretion of both
      ACTH and vasopressin in response to constriction of the inferior vena cava and,
      in the case of vasopressin, in response to hemorrhage. Although hemorrhage
      initiated secretion of ACTH was significantly reduced by injection of muscimol
      into the A1 area, it was not completely eliminated by these injections or by
      injections of muscimol into a more rostrocaudally extensive region of the medulla
      oblongata. We conclude that the net output from the NTS tonically inhibits
      secretion of both ACTH and vasopressin, reflecting tonic baroreceptor tone. For
      vasopressin, the pathway from the NTS to the hypothalamus is dependent on a
      synapse in the A1 area. For ACTH, there are pathways to the hypothalamus that do
      not synapse in the A1 area, but neurons in this region do have an excitatory
      effect on secretion of ACTH.

PMID- 1352434
TI  - NG-monomethyl-L-arginine and nitroarginine potentiate pressor responsiveness of
      vasoconstrictors in conscious rats.
AB  - NG-monomethyl-L-arginine (NMA) and nitroarginine have been reported to be
      competitive inhibitors of the production of endothelium-derived relaxing factor
      (EDRF). In chronically instrumented conscious rats, we observed that the pressor
      response of NMA was attenuated by pretreatment with L-arginine but not by
      pretreatment with D-arginine, phentolamine, or meclofenamate. Inhibitors of the
      renin-angiotensin system, captopril and [Sar1,Ile5,Thr8]angiotensin II, did not
      significantly affect the pressor response of NMA, either. Ten to fifteen minutes
      after bolus administration of 7-15 mg/kg NMA, when baseline blood pressure was
      virtually restored, the pressor responses of angiotensin II (ANG II),
      norepinephrine, and arginine vasopressin were significantly potentiated by
      approximately 30-40% compared with control values. This potentiation was
      prevented by pretreatment with L- but not D-arginine. It was also observed in
      conscious rats subjected to ganglionic blockade. Likewise, the pressor responses
      of ANG II were significantly increased during infusions of 2 and 5 micrograms/min
      nitroarginine methyl ester (NAME), dosages that raised baseline blood pressure by
      6 +/- 2 and 15 +/- 3 mmHg, respectively. During administration of 5 and 50
      micrograms/min NAME, hypotensive responses of methacholine and histamine were
      only modestly attenuated compared with the responses recorded during infusions of
      phenylephrine, which raised resting blood pressure to comparable levels. Finally,
      in freshly isolated rat aorta, NMA inhibited basal and stimulated production of
      guanosine 3',5'-cyclic monophosphate in a manner comparable to reduced
      hemoglobin, a known inhibitor of EDRF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352435
TI  - The efficacy of MR imaging in subdural empyema.
AB  - MRI findings of a 14-year-old boy with subdural empyema (SE) are reported and
      compared with those of serial CT-scan. He was admitted with fever, headache,
      right hemiplegia and facial palsy. Initial enhanced CT-scan revealed a slit left
      lateral ventricle and a shift in the mid-line structures, but failed to detect
      any SE. MRI at 10 days after admission clearly demonstrated SE as an area of low
      intensity on T1-weight (T1WI) and very high intensity on T2-weight (T2WI). Post
      contrast enhanced MRI (CE-MRI), using Gd-DTPA, showed a contrast enhancement in
      the wall of SE. However, no definite parenchymal abnormal intensity areas were
      detected, suggesting that the diagnosis was made sufficiently early for timely
      treatment and good neurological outcome. CE-MRI proved to be a more powerful and
      better diagnostic procedure than enhanced CT-scan, and was very useful in
      determining the state and development of the disease.

PMID- 1352436
TI  - XVth Congress of the European Academy of Allergology and Clinical Immunology.
      Paris, France, 10-15 May 1992. Abstracts.

PMID- 1352437
TI  - The biochemistry of the neuron: methods and calculations for the analysis of
      neurotransmitter secretion from populations of single cells.
AB  - Methods and calculations for the continuous measurement of secretion of
      radiolabeled neurotransmitter from cultured neuronal cells are demonstrated. The
      method is used to measure the secretion of [3H]-norepinephrine by neuronally
      differentiated PC12 cells in response to a stepwise presentation of a
      depolarizing stimulus. The response is known to be biphasic, consisting of a
      transient burst of secretion (phase I) followed by a plateau of secretion (phase
      II). Habituation, in which cellular secretion is lowered by repetitive
      stimulation of the cells, is shown here to lower uniformly both phases of
      secretion. There thus appears to be a mechanism within the cell that holds
      constant the proportions of phase I and phase II secretion even though the
      overall size of the secretory response may be regulated as a consequence of
      repetitive stimulation. The feasibility of the method for widespread application
      to cultured neuronal cells is demonstrated.

PMID- 1352438
TI  - A strategy for discovering biologically active compounds with high probability in
      traditional Chinese herb remedies: an application of saiboku-to in bronchial
      asthma.
AB  - A novel strategy for discovering biologically active components in traditional
      Chinese herb remedies was performed from a pharmacokinetic view. The hypothesis
      was that the active compounds should appear in blood and urine with appropriate
      blood concentrations and urinary excretion rates after the administration of
      herbal-extract mixtures. In this research, we applied our procedures to Saiboku
      To, one of the most popular Chinese herbal medicines in Japan. Consisting of 10
      different plant extracts, it is used for the treatment of bronchial asthma. The
      analytical method adopted was a rapid-flow fractionation (RFF) for extraction
      fractionation of lipophilic components in urine followed by silica-gel high
      performance liquid chromatography (HPLC) equipped with a multichannel ultraviolet
      (uv) absorption detector. beta-D-Glucuronidase-treated urine samples collected
      before and after the administration of Saiboku-To to healthy and asthmatic
      subjects were treated with the RFF apparatus to afford three pH-dependent
      fractions: strongly acidic (S), weakly acidic (W), and neutral (N). HPLC of these
      fractions, monitored by the multichannel uv detector, showed three new peaks in
      the postadministrative urine: one in the N fraction, two in the W fraction, and
      none in the S fraction. A compound in the N fraction was identified with
      authentic magnolol, a major component in Magnolia officinalis. Two compounds in
      the W fraction were identified by comparison with authentic samples as 8,9
      dihydroxydihydromagnolol and liquiritigenin, metabolites previously isolated from
      M. officinalis and Glycyrrhiza glabra, respectively.

PMID- 1352439
TI  - Tumor-specific methylation patterns of erbB2 (HER2/neu) sequences in gastro
      intestinal cancer.
AB  - To determine whether the sporadically occurring amplification of the oncogene
      erbB2/HER2 in gastrointestinal carcinomas is associated with additional changes
      of this sequence, DNA from 17 colorectal and 5 stomach carcinomas was analyzed
      for copy number, sequence rearrangement and DNA methylation by Southern blot
      hybridization. Amplification was detected in two cases. By applying the
      isochizomers Hpall and Mspl we tested for alterations in the DNA methylation
      status. Whereas in colon tumors with non-amplified erbB2 this status was
      unchanged, one case with erbB2 amplification showed additional MspI bands
      indicating a methylation of the amplified gene sequences. In stomach carcinoma,
      however, we detected differences between tumor and mucosa samples but not between
      amplified and non-amplified tumor samples. Independent of the DNA methylation
      status, significant amounts of the erbB2 oncoprotein were detected in the cases
      with gene amplification; weaker immunostaining of erbB2 was also seen in a few
      additional tumors.

PMID- 1352440
TI  - Inflammatory breast carcinoma: an immunohistochemical study using monoclonal anti
      pHER-2/neu, pS2, cathepsin, ER and PR.
AB  - Immunocytochemical assays were performed on frozen sections of inflammatory
      breast carcinomas (n = 22) using the following monoclonal antibodies (MoAb): anti
      pHER2/neu, cathepsin, pS2, ER, PR and MoAb Ki67. The distribution of these
      proteins, known as prognostic indicators, was evaluated with an image analysis
      system (SAMBA, Alcatel TITN, France). On standard HE stained paraffin sections,
      only about 50% of inflammatory breast tumors exhibited intradermal tumor cell
      emboli. All tumors were strongly pHER/2neu positive. All tumors also, but to a
      lesser degree, were cathepsin and ki67 positive. Conversely, less than 40% were
      faintly ER, PR and pS2 immunoreactive. The results correlated with the high
      degree of malignancy of inflammatory breast carcinomas. Therefore the immuno
      detection of these markers in addition to standard histological techniques
      appears to be a useful tool to evaluate the degree of malignancy of breast
      carcinomas.

PMID- 1352441
TI  - Action of long-chain fatty acids on protein kinase C activity: comparison of
      omega-6 and omega-3 fatty acids.
AB  - The results presented in this paper indicate that long chain free fatty acids
      have a dual modulatory effect on Protein Kinase C (PKC) activity purified from
      rat colon. Saturated (stearic) and monounsaturated (oleic) fatty acids are weak
      activators of PKC in the absence of phosphatidyl serine (PS) and diolein (DO),
      but have no significant effect on the PS/DO stimulated activity. Increasing the
      degree of unsaturation of the fatty acid, such as linolenic, arachidonic and
      eicosapentaenoic acids, also increases their stimulatory action toward
      unstimulated PKC, as well as their inhibition of PS/DO stimulated enzyme
      activity. Within this group of fatty acids there is no significant difference in
      the response of PKC toward omega-6 versus omega-3 type fatty acids. However,
      docosahexaenoic acid, a 22 carbon omega-3 polyunsaturated fatty acid found
      primarily in fish oil affected PKC differently from all other fatty acids
      studied. This compound was unable to stimulate dormant PKC activity, but was a
      highly potent inhibitor of PS/DO stimulated PKC. It is hypothesized that the
      inhibitory action of this omega-3 fatty acid may contribute to the protective
      role of fish oil consumption on colon tumorigenesis.

PMID- 1352442
TI  - Evidence that some Frankia sp. strains are able to cross boundaries between Alnus
      and Elaeagnus host specificity groups.
AB  - Phenotypic and genotypic methods were used to prove the existence of Frankia
      strains isolated from an Elaeagnus sp. that are able to cross the inoculation
      barriers and infect Alnus spp. also. Repeated cycles of inoculation, nodulation,
      and reisolation were performed under axenic conditions. Frankia wild-type strain
      UFI 13270257 and three of its coisolates did exhibit complete infectivity and
      effectiveness on Elaeagnus spp. and Hippophae rhamnoides and variable infectivity
      on Alnus spp. Microscopical observation of host plant roots showed that these
      strains are able to infect Alnus spp. by penetrating deformed root hairs.
      Reisolates obtained from nodules induced on monoxenic Alnus glutinosa, Alnus
      incana, and Elaeagnus angustifolia resembled the parent strains in host
      infectivity range, in planta and in vitro morphophysiology, isoenzymes, and nif
      and rrn restriction fragment length polymorphisms, thus fulfilling Koch's
      postulates on both host plant genera. Alnus and Elaeagnus group-specific
      polymerase chain reaction DNA amplifications, DNA-DNA hybridizations, and partial
      gene sequences coding for 16S rRNA provided evidence for the genetic uniformity
      of wild-type strains and their inclusion into one and the same genomic species,
      clearly belonging to the Elaeagnus group of Frankia species.

PMID- 1352443
TI  - Effect of acetylene on nitrous oxide reduction and sulfide oxidation in batch and
      gradient cultures of Thiobacillus denitrificans.
AB  - Anaerobic enrichment cultures with H2S and N2O as substrates which were
      inoculated with a biofilm sample showed rapid growth and gas formation after 2 to
      3 days at 27 degrees C. By using the deep-agar dilution technique, a pure culture
      was obtained. The strain was tentatively identified as Thiobacillus
      denitrificans. The isolate was used for batch and gradient culture studies under
      denitrifying conditions, oxidizing H2S with concomitant reduction of N2O to N2.
      In batch culture, oxidation of H2S was stepwise, with transient accumulation of
      elemental sulfur; the final oxidation product was SO4(2-). In gradient culture,
      there was no notable accumulation of elemental sulfur and microsensor
      measurements of H2S and N2O showed that H2S was oxidized directly to SO4(2-). In
      the presence of C2H2, however, oxidation of H2S stopped at the level of elemental
      sulfur and no SO4(2-) was produced in either batch or gradient cultures. This is
      a hitherto unknown inhibitory effect of C2H2. The inhibition is suggested to
      occur at the level of sulfite reductase, which catalyzes the oxidation of
      elemental sulfur to SO3(2-) in T. denitrificans. However, reduction of N2O in
      this strain was, surprisingly, not affected by C2H2. The isolate is the first
      chemolithoautotrophic organism shown to reduce N2O in the presence of C2H2.
      Denitrification in natural ecosystems is often quantified as N2O accumulation
      after C2H2 addition. However, the presence of large numbers of similar organisms
      with C2H2-insensitive N2O reduction could lead to underestimation of in situ
      rates.

PMID- 1352444
TI  - Measurements of the distribution of adenylate concentrations and adenylate energy
      charge across Pseudomonas aeruginosa biofilms.
AB  - Adenine nucleotide pools and adenylate energy charge distributions were
      determined by using a laboratory-generated quasi-steady-state Pseudomonas
      aeruginosa biofilm. The method used involved freezing and sectioning of the
      intact biofilm, followed by extraction and assay of the adenylates in the
      sectioned material. Results indicated an increase in adenylate energy charge of
      about 0.2 units from the bottom to the surface of the biofilm. However, energy
      charge values were generally low throughout the biofilm, reaching a maximum of
      only 0.6 units. Of the adenylates measured, AMP was the predominant nucleotide,
      especially in the deeper parts of the biofilm profile.

PMID- 1352445
TI  - Amino acid composition of dentine in permanent human teeth.
AB  - Dentine of permanent mandibular incisors from nine individuals was hydrolysed and
      the amino acid composition determined by ion-exchange chromatography against a
      standard calibrant of 41 amino acids. Nineteen amino acids were detected,
      including small quantities of 1-methylhistidine and asparagine, two amino acids
      whose existence had apparently not been recorded before in human dentine. The
      total content of hydroxylysine plus lysine varied between 2.6 and 3.3 residues
      per 100 (SD, 0.74) in different teeth, which therefore did not support previous
      studies that had proposed a constant total value. This and other quantifiable
      differences between present and previous findings may be the result of the
      different methods and the influence of dietary and other regional factors on
      dentinogenesis.

PMID- 1352447
TI  - Differences in 2-oxoglutarate dehydrogenase regulation in liver and kidney.
AB  - In response to acidosis, renal ammoniagenesis is stimulated, enhancing urinary
      buffering power, while hepatic ammoniagenesis and ureagenesis decrease, so as to
      spare bicarbonate consumed in the urea cycle. 2-Oxoglutarate (2-OG) levels can
      regulate ammoniagenesis in kidney and gluconeogenesis in liver and kidney. Since
      the activity of 2-oxoglutarate dehydrogenase (2-OGDH) has an important influence
      on cellular levels of 2-OG, this study evaluated the effects of pH on 2-OGDH in
      liver and kidney and found that: (1) the isolated enzyme from both organs has the
      same pH-sensitivity; (2) 2-OGDH flux measured in intact mitochondria was
      inhibited by increasing H+ in liver, but stimulated in kidney; (3) transport of 2
      OG into the mitochondria was not rate-limiting; (4) liver mitochondrial 2-OGDH
      exhibited a strong preference for 2-OG generated within the mitochondria from
      glutamate-oxaloacetate transaminase (GOT), suggesting that channelling between
      GOT and 2-OGDH occurs. Since complexation between 2-OGDH and GOT occurs in vitro,
      we propose that the degree of complexation is higher in liver than in kidney,
      such that most of the 2-OGDH may be complexed to GOT in liver. In the liver the
      inherent H(+)-sensitivity of 2-OGDH is masked by the pH-sensitivity of GOT and
      the glutamate-aspartate carrier.

PMID- 1352446
TI  - Purification and characterization of the blue-green rat phaeochromocytoma (PC12)
      tyrosine hydroxylase with a dopamine-Fe(III) complex. Reversal of the endogenous
      feedback inhibition by phosphorylation of serine-40.
AB  - Tyrosine hydroxylase (TH) was purified from tumours of rat phaeochromocytoma
      (PC12) cells by a three-step purification procedure giving 30 mg of pure enzyme
      in 3 days. The enzyme sedimented with an S(eo),w value of 9.2 S and revealed an
      apparent subunit molecular mass of 62 kDa with a minor 60 kDa component. Two
      dimensional gel isoelectric focusing/electrophoresis and tryptic digestion
      revealed that the heterogeneity could be accounted for by limited proteolysis of
      the 62 kDa component and the presence of covalently bound phosphate. The enzyme
      had a strong blue-green colour (epsilon 700 = 3.1 +/- 0.2 mM-iron-1.cm-1). The
      resonance Raman spectrum obtained with lambda excitation = 605 nm revealed the
      presence of an Fe(III)-catecholamine complex in the isolate enzyme, similar to
      that observed in the bovine adrenal enzyme [Andersson, Cox, Que, Flatmark &
      Haavik (1988) J. Biol. Chem. 263, 18621-18626]. In the rat PC12 enzyme, all of
      the iron present (0.53 +/- 0.03 atom per subunit) seems to be chelated by the
      feedback inhibitors (0.49 +/- 0.05 mol of dopamine and 0.10 +/- 0.03 mol of
      noradrenaline per mol of subunit). The e.p.r. spectra at 3.6 K show g-values at
      7.0, 5.2 and 1.9 as observed for other catecholate-complexed enzymes. After
      phosphorylation of serine-40 and addition of L-tyrosine a new rhombic (magnitude
      of E/D = 0.33) e.p.r. species could be observed. Phosphorylation of serine-40 by
      cyclic AMP-dependent protein kinase increased the catalytic activity; depending
      on assay conditions, up to 80-110-fold activation could be observed when measured
      at high TH (i.e. high endogenous catecholamine) concentration.

PMID- 1352448
TI  - G-protein-mediated activation of turkey erythrocyte phospholipase C by beta
      adrenergic and P2y-purinergic receptors.
AB  - Isoprenaline, previously known only to stimulate adenylate cyclase via the
      stimulatory G-protein, Gs, activates turkey erythrocyte ghost phospholipase C
      (PLC) in a dose-dependent manner when GTP or guanosine 5'-[gamma
      thio]triphosphate (GTP[S]) is present. The effect is specific in that it is
      abolished by beta-adrenergic-receptor antagonists. Stimulation of adenosine
      receptors, which also couple to adenylate cyclase via Gs in turkey erythrocytes,
      does not activate PLC, indicating that the stimulation observed in the presence
      of isoprenaline is not due to Gs activation. Furthermore, the stimulation seen is
      independent of cyclic AMP production. Purified turkey erythrocyte PLC is
      activated in an adenosine 5'-[beta-thio]diphosphate (ADP[S]; a P2y-purinergic
      receptor agonist)- or isoprenaline-regulated manner when reconstituted with
      turkey erythrocyte ghosts, demonstrating that a single species of PLC effector
      enzyme can be regulated by both the purinergic and the beta-adrenergic receptor
      populations present in turkey erythrocyte membranes. Pretreatment of intact
      turkey erythrocytes with the P2y agonist ADP[S] causes decreased PLC
      responsiveness of subsequent ghost preparations to ADP[S] stimulation, although
      responses to isoprenaline are unaffected (homologous desensitization). In
      contrast, pretreatment of intact erythrocytes with isoprenaline results in
      heterologous desensitization of both the P2y and the beta-adrenergic receptors.
      These effects occur at the level of receptor-G-protein coupling, since PLC
      stimulation by GTP[S] (which directly activates G-proteins) in the absence of
      agonists is unaffected.

PMID- 1352449
TI  - HLA class II sequence polymorphisms and susceptibility to rheumatoid arthritis in
      Greeks. The HLA-DR beta shared-epitope hypothesis accounts for the disease in
      only a minority of Greek patients.
AB  - OBJECTIVE: In Northern Europeans, rheumatoid arthritis (RA) is strongly
      associated with a relatively conserved pentapeptide sequence of HLA-DR beta found
      notably in the HLA-DR4 subtypes Dw4 and Dw14 and in DR1. A previous serologic
      study of HLA class II polymorphism in a Greek population with RA failed to show
      significant associations with any antigen. METHODS: We characterized HLA-DRB
      polymorphisms in Greek patients with RA and in control subjects by restriction
      fragment length polymorphism analysis. Allelic DRB subtypes were examined by
      polymerase chain reaction amplification and oligonucleotide hybridization.
      RESULTS: DNA analysis in the RA patients showed that although individual HLA-DR
      allelic associations were weak, a relatively conserved HLA-DR beta motif was
      significantly associated with RA in this population of Greek patients. The third
      hypervariable region amino acid sequences QRRAA, QKRAA, or RRRAA were found in
      the HLA-DR beta 1 of 43.5% of the RA patients versus 15.5% of the controls
      (uncorrected P = 0.00004). CONCLUSION: Sequences shown to influence
      susceptibility to RA in patients in the UK also play a role in patients in
      Greece. However, 57% of Greek patients lack the putative HLA-DR beta motif, which
      suggests that considerable immunogenetic heterogeneity underlies disease
      susceptibility in this population.

PMID- 1352450
TI  - T cell receptor gamma variable gene locus polymorphism in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: We sought new susceptibility markers for rheumatoid arthritis (RA)
      among the T cell receptor gamma (TCR gamma) genes. METHODS: We analyzed
      restriction fragment length polymorphisms (RFLP) of the first variable subgroup
      of TCR gamma genes in a group of French control subjects and a group of French RA
      patients. RESULTS: No significant difference in Eco RI RFLP was found between the
      2 study populations: Allele frequencies were virtually identical. There was no
      polymorphism using Hind III. CONCLUSION: These results exclude TCRV gamma I
      polymorphism as a disease susceptibility marker in RA.

PMID- 1352451
TI  - Follicular dendritic cells and their role in HIV infection.
AB  - Recently, much attention has focussed on the role of follicular dendritic cells
      as a reservoir of infectious particles in retroviral, particularly HIV,
      infection. In this report from a recent meeting, Johannes Gerdes and Hans-Dieter
      Flad describe these studies in the context of a growing awareness of the
      morphological, phenotypic and functional heterogeneity of the cells.

PMID- 1352452
TI  - Motor activity and the mesotelencephalic dopamine function. I. High-resolution
      temporal and genetic analysis of open-field behavior.
AB  - In a genetic selection experiment whose goal was to construct congenic
      neurological animal model lines with different mesotelencephalic dopamine
      systems, we produced foundation F2 generations derived from crosses
      (C57BL/6ByJXBALB/cJ and C57BL/6ByJXCXBI/ByJ) between highly inbred mouse lines
      with different dopamine systems. In this report, temporal distribution, latency,
      and genetic variability of open-field (OF) behavioral variables were investigated
      in order to establish a behavioral profile for the various generations and to
      provide behavioral data as a first step towards multivariate studies on
      correlations between OF behaviors and mesencephalic and striatal tyrosine
      hydroxylase activity. Analysis of the behavioral data provided evidence that
      measures of the open-field behaviors varied significantly across time segments of
      the test and that the temporal profiles of several behavioral variables were
      genotype-dependent. It is suggested that (1) OF behaviors have dynamic temporal
      profiles, and (2) temporal-genetic analysis can be a useful auxiliary method in
      the functional interpretation of behavior.

PMID- 1352453
TI  - 4th Scandinavian Breast Cancer Symposium. Porvoo, Finland. June 3-5, 1991.

PMID- 1352454
TI  - A chimeric EGFR/neu receptor in functional analysis of the neu oncoprotein.
AB  - As the factor binding to the neu protein has been unknown, it has not been
      possible to confirm experimentally the proposed growth-factor receptor like
      functions of the neu protein. To approach this problem we constructed a
      recombinant receptor which enabled ligand regulation of the neu tyrosine kinase.
      The hybrid receptor consisted of the extracellular ligand binding, transmembrane
      and protein kinase C-substrate domains joined to the intracellular tyrosine
      kinase and carboxyl-terminal domains of the neu protein. Several properties of
      NIH3T3 cells carrying this construct were tested. We obtained the first
      experimental evidence that the neu proto-oncogene has mitogenic and transforming
      activities only in the presence of a ligand stimulating its tyrosine kinase
      activity. Various cellular and molecular biological parameters indicated that the
      chimeric receptor behaved very similarly to the EGFR. Also, this chimeric
      receptor has allowed us to compare the constitutive oncogenic and the ligand
      activated non-oncogenic activities of the neu tyrosine kinase. In the future we
      plan to focus on characterization of possible differences between EGFR and neu
      signalling in more differentiated cellular backgrounds.

PMID- 1352455
TI  - Mechanisms of multidrug resistance in cancer treatment.
AB  - Advanced breast cancer responds to a range of cytotoxic agents, but resistance
      always develops. Understanding the mechanisms of resistance may provide new
      therapeutic options. There are several major groups of resistance mechanisms. 1)
      The multidrug resistant phenotype. This is due to a membrane pump that can
      extrude a wide range of anticancer drugs--the P-glycoprotein. It is inhibited by
      a range of clinically used calcium channel blockers such as nifedipine and
      verapamil. Several other membrane proteins of 180 KD, 170 KD, 300 KD and 85 KD
      have been reported and are associated with MDR. 2) Glutathione transferences and
      detoxification mechanisms. These are a multigene family of enzymes that conjugate
      glutathione to chemically reactive groups. There are 3 major groups of enzymes-
      acidic, basic and neutral. They have been implicated in resistance to
      doxorubicin, melphalan cisplatinum chlorambucil and other alkylating agents.
      Other protecting systems include metallothionein and selenium dependent
      glutathione peroxidase. HSP27 confers doxorubicin resistance. 3) Topoisomerase
      II. DNA topoisomerases are involved in several aspects of DNA metabolism in
      particular genetic recombination, DNA transcription, chromosome segregation. They
      are a target for doxorubicin, mitoxantrone, VP16. Low levels of expression are
      associated with resistance. However, it is oestrogen inducible and this may be of
      therapeutic value. A novel topo IIb which is more drug resistant has been
      reported. 4) DNA repair. A score or more of genes are involved in the repair of
      DNA damage by drugs and radiation. Defective DNA repair may predispose to cancer
      of the breast and be responsible for adverse radiation reactions. Enhanced repair
      has been shown to be a mechanism of cisplatinum resistance. Several genes are
      inducible by DNA damage and may confer resistance e.g. A45. 5) Drug activation.
      Mitomycin C as well as cyclophosphamide and VP16 require activation for their
      effects. Low levels of cytochrome p450 reductase are associated with MMC
      resistance.

PMID- 1352457
TI  - Osteosarcoma and adult soft tissue sarcomas: present trends. Proceedings of
      international symposium. Aviano, Italy, March 21-22, 1991.

PMID- 1352456
TI  - Multiple endocrine neoplasia type 2 with malignant pheochromocytoma--long term
      follow-up of a case by 131I-meta-iodobenzylguanidine scintigraphy.
AB  - The case of a 33-year-old Japanese man, who has Multiple Endocrine Neoplasia Type
      2 (MEN IIa) (Sipple's syndrome) with malignant pheochromocytoma, is reported. He
      had survived for twelve years since the initial diagnosis of malignant
      pheochromocytoma. Within this period, he had undergone 131I-meta
      iodobenzylguanidine scintigraphy twice, in 1983 and 1990. This is the first case
      in Japan of a longterm surviving patient with malignant pheochromocytoma followed
      up by 131I-MIBG scintigraphy. Although he had no exacerbation of clinical
      symptoms or urinary catecholamine levels, second scintigraphy clearly showed an
      increase in the tumor size, new metastasis of the malignant pheochromocytoma and
      exacerbation of the medullary thyroid carcinoma. Compared with any other
      roentgenological device and hormonal data, 131I-MIBG scintigraphy was seen to be
      a good tool for evaluating the localization and the progression of tumors. 131I
      MIBG scintigraphy is a useful procedure not only for initial diagnosis but also
      for judging progression in a case of advanced malignant pheochromocytoma.

PMID- 1352458
TI  - Intracranial germ cell tumour in association with cryptorchidism.
AB  - An intracranial germ cell tumour (GCT) in a patient with cryptorchidism is
      presented. The known association between testicular GCTs and cryptorchidism
      suggests a possible common predisposition for gonadal and extragonadal tumours.
      To confirm this the frequency of the reported association needs to be defined.

PMID- 1352459
TI  - Response of V beta 8.1+ T cell clones to self Mls-1a: implications for the origin
      of autoreactive T cells.
AB  - Clonal deletion and anergy are two major mechanisms of self-tolerance. However,
      the molecular mechanisms underlying clonal deletion and anergy, as well as the
      threshold of TCR affinity/avidity required for these processes, are not known.
      Expression of the V beta 8.1 TCR correlates with the reactivity of the T cells to
      the minor lymphocyte stimulating locus-1a (Mls-1a) and T cells expressing this
      TCR are deleted in the thymus of Mls-1a mice. Similarly, in TCR V beta 8.1
      transgenic mice, the number of CD4+CD8-T cells is reduced in Mls-1a mice.
      However, small numbers of CD4+CD8-T cells remain in the periphery of adult Mls-1a
      transgenic mice. We have generated T cell clones from TCR V beta 8.1 transgenic
      mice by stimulation of lymph node T cells with C57BL/6 alloantigens.
      Interestingly, CD4+CD8-V beta 8.1+ clones isolated from the transgenic mice of
      Mls-1a background responded to the self-antigen Mls-1a, to which they did not
      respond in primary assay. Reactive patterns of the clones were compared with
      clones derived from Mls-1b mice. Proliferation and cytokine production of the
      clones from Mls-1a mice to the self-antigen Mls-1a were generally reduced when
      compared with clones from Mls-1b mice. More importantly, T cell clones from Mls
      1a mice required more Mls-1a antigen for their activation, and were more
      susceptible to the inhibitory effects of anti-CD4 antibody on the proliferative
      responses to Mls-1a than those from Mls-1b mice. These results suggest that the T
      cell receptor on clones derived from Mls-1a mice have functional but reduced
      affinity/avidity for self-antigen Mls-1a.

PMID- 1352460
TI  - Influence of HLA-DR2, HLA-DPw4, and T cell receptor alpha chain genes on the
      susceptibility to multiple sclerosis.
AB  - In view of our recent report that T cell receptor (TCR) alpha chain restriction
      fragment length polymorphism (RFLP) is associated with multiple sclerosis (MS),
      we have assessed the possibility that HLA-DR2, HLA-DPw4, and TCR alpha chain
      RFLPs may interact to increase the risk of developing MS. Detection of TCR alpha
      chain polymorphisms, and HLA-DR and -DP typing were carried out by RFLP analysis
      on MS patients and healthy controls from the Melbourne metropolitan area.
      Interaction effects among these loci in producing susceptibility to MS were
      assessed by hierarchial log-linear analysis. Although HLA-DR2 was significantly
      associated with MS (chi 2 = 9.30, P = 0.002), no interactive effect between MS
      and HLA-DPw4 was observed. Significant interactions were observed with MS and
      both C alpha and V alpha, with the strongest effect seen with C alpha (chi 2 =
      21.30, P less than 0.001). The combination of DR2/C alpha imparted a relative
      risk of 47. However, when the data were analysed for four and three way
      interactions, no significant effects were seen with MS, DR2, DPw4, V alpha, and C
      alpha, implying that the combined presence of these polymorphic markers is not
      essential for increasing susceptibility to MS.

PMID- 1352461
TI  - Antigen-independent adhesion of CD45RA (naive) and CD45RO (memory) CD4 T cells to
      B cells.
AB  - We found that naive (CD45RA+) CD4 T cells have a lower capacity of adhesion to
      Epstein-Barr virus (EBV) immortalized B cells than memory (CD45RO+) CD4 T cells,
      as judged by conjugate formation. This would appear to be due to differences in
      the expression of adhesion molecules [lymphocyte function-associated antigen
      (LFA)-1, CD2]. However, kinetic studies showed that the degree of adhesion of
      naive T cells to B cells was stable over 60 min while that of memory T cells,
      like that of unseparated CD4 T cells, was characterized by a rapid formation and
      rapid dissociation of conjugates. This could be explained by a difference in the
      sensitivity of naive and memory CD4 T cells to down-regulation of antigen
      independent adhesion by CD4-MHC class II interaction. Indeed, memory T cells also
      adhered stably to MHC class II(-) B cells. The adhesion of memory T cells, but
      not naive T cells, to MHC class II(+) B cells was sensitive to inhibition by
      OKT4a an anti-CD4 antibody, human immunodeficiency (HIV) gp160 (env) protein and
      a 12-mer peptide encompassing the 35-46 sequence of the HLA, DR beta 1 domain and
      previously shown to inhibit activation of HLA class II-restricted CD4 T cell
      responses. Since MHC class II expression did not influence the degree of
      conjugate formation by naive or memory CD4 T cells with B cells, CD4-MHC class II
      interaction does not appear to be involved in binding itself, but may down
      regulate the adhesion of memory but not naive CD4 T cells.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1352462
TI  - Making sense of viral gene sequences. Coevolution of Viruses, their Hosts and
      Vectors sponsored by Fundacion Juan March, Madrid, Spain, December 9-11, 1991.

PMID- 1352463
TI  - The cell biology of membrane transport. Cell Biology and Membrane Transport
      Processes, New Haven, CT, USA, December 5-6, 1991.

PMID- 1352464
TI  - Cardiac allograft vascular disease: a basic science and clinical review.
      Proceedings of an International Conference. St. Louis, Missouri, October 25-26,
      1991.

PMID- 1352465
TI  - Angiopeptin: a treatment for accelerated myointimal hyperplasia?
AB  - Extensive smooth muscle cell proliferation is the major event leading to the
      narrowing or occlusion of the lumen of the coronary arteries of patients
      undergoing heart transplantation or percutaneous transluminal coronary
      angioplasty. The smooth muscle cell proliferation in transplant atherosclerosis
      may be initiated by immunologic events, allowing the vascular smooth muscle cells
      to respond with migration and proliferation to circulating growth factors as well
      as chemoattractants and growth factors released by inflammatory cells and smooth
      muscle cells themselves. The somatostatin analog angiopeptin is a cyclic
      octapeptide that has different binding affinities for different somatostatin
      receptors compared with the parent compound itself. The antiproliferative effects
      of angiopeptin have been demonstrated in vitro in several tumor cell lines. In a
      rabbit model of heterotopic heart transplant-accelerated coronary
      atherosclerosis, angiopeptin has been shown to attenuate myointimal hyperplasia.
      Further studies in simpler models of myointimal hyperplasia have shown that
      angiopeptin will inhibit smooth muscle cell proliferation after vascular injury.
      Further, angiopeptin inhibits thymidine uptake in vitro in pig coronary arteries.
      Angiopeptin also exerts its inhibitory effect at a very early stage after injury:
      an 8-hour delay of treatment abolishes the inhibitory effect of angiopeptin on
      smooth muscle cell proliferation (intimal hyperplasia). On the basis of the
      experimental data, clinical studies of the inhibitory effect of angiopeptin on
      prevention of transplant atherosclerosis in heart transplant patients and
      prevention of restenosis after coronary artery angioplasty are ongoing, as well
      as are studies in patients undergoing saphenous vein coronary artery bypass
      surgery.

PMID- 1352466
TI  - cAMP-dependent protein kinase activation mediated by beta 3-adrenergic receptors
      parallels lipolysis in rat adipocytes.
AB  - Catecholamine-induced lipolysis is chiefly mediated through the recently
      characterized beta 3-adrenergic receptor (AR) in rat adipocytes. Discrepancies
      between the ability of beta 3-AR agonists to stimulate adenylyl cyclase and the
      resulting lipolysis were recently reported. cAMP-dependent protein kinase (A
      kinase) activation induced by these agonists was compared to lipolysis. Agonist
      potencies were similar for A-kinase activity ratios and lipolysis. The same A
      kinase activity ratio to lipolysis relationship was found for the beta 3-AR
      agonists tested.

PMID- 1352467
TI  - The Peptide Protein Bridge. Proceedings from an international symposium. Toronto,
      Canada, June 10-14, 1991.

PMID- 1352469
TI  - Neural transplants: prospects for Alzheimer's disease.
AB  - Neural transplantation has emerged as a useful tool for neurobiologists to
      investigate basic mechanisms of brain function, as well as potential therapies
      for neurodegenerative diseases. At present, intracerebral grafting is not a
      therapy for Alzheimer's disease (AD) or dementia. However, recent developments
      using molecular biological methodologies in combination with grafting have opened
      new avenues to explore new therapeutic approaches and address questions of
      etiology.

PMID- 1352470
TI  - Basic mechanisms of the epilepsies.
AB  - To understand the fundamental pathophysiology of the epilepsies, the chronic
      changes of structure and function in the brain that distinguish them must be
      identified and the basic mechanisms by which these changes come about need to be
      delineated. Recently, progress has been made along these lines, identifying
      morphological and operational differences in epileptic brains, both those from
      humans and those from animals, as well as alterations in gene activation brought
      about by seizures.

PMID- 1352468
TI  - Chlorophyll a/b-binding protein genes are differentially expressed during soybean
      development.
AB  - The levels of chlorophyll a/b-binding protein (Cab) gene polysomal poly(A)+ mRNA
      were quantitated throughout the development of Glycine max L. Cab mRNAs were
      abundant in young expanding leaves, representing 6.1% of the leaf mRNA
      population. Lower Cab mRNA levels were present in embryos, stems, and cotyledons
      of developing seedlings; the lowest levels were found in roots where they
      accounted for 0.04% of the polysomal poly(A)+ mRNA of this organ. To determine
      the contribution of different members of the Cab gene family to the Cab mRNA
      populations, a quantitative S1 nuclease reconstruction assay was developed. Cab3,
      Cab4, and Cab5 mRNAs were detected in all stages examined during soybean
      development but their levels underwent differential changes. Cab3 encodes the
      most abundant Cab mRNA in young leaves, developing embryos, and in Stage VII
      cotyledons from the developing soybean seedling. The levels of Cab mRNAs were
      compared to the levels of ribulose-1,5-bisphosphate carboxylase small subunit
      gene mRNA and differences in their patterns of accumulation were noted.
      Collectively these data indicate that during soybean embryogenesis developmental
      control mechanisms supersede light-regulatory signals.

PMID- 1352471
TI  - Backbone modifications in somatostatin analogues: relation between conformation
      and activity.
AB  - Twenty cyclic and linear analogues of somatostatin have been compared with
      respect to their conformational behavior and biological activity. It appears that
      all active compounds have in common a well defined, predominant backbone
      conformation. For linear peptides, this conformation can only be detected at low
      (-80 degrees C) temperature by NMR measurements. Selectivity is suggested to be
      determined by the nature and topology of the side chains linked to this common
      backbone conformation. The side chain conformation is also only accessible for
      NOE measurements in the low temperature range.

PMID- 1352472
TI  - The psychopharmacology of social phobia.
AB  - The use of psychotropic drugs in the treatment of social phobia has occurred only
      recently. The author reviews the available studies which suggest that medications
      in the beta-blocker group, the monoamine oxidase inhibitors, the benzodiazepines,
      and possibly others are useful in the treatment of social phobia.

PMID- 1352473
TI  - The versatile superficial inferior epigastric artery free flap.
AB  - A series of 27 successful Superficial Inferior Epigastric Artery free flaps were
      analysed for a number of clinical and surgical variables. The anatomy and
      surgical technique of the flap are detailed and its advantages and disadvantages
      relative to other free flaps used for soft tissue contour are considered.
      Analysis of the variety of recipient sites of this flap is presented, as are
      details of the vascular pedicle and our experience with its constancy. It has
      been found to be a safe flap in experienced hands, with an aesthetic donor site
      scar, no functional loss and it lends itself to subsequent recontouring with
      suction assisted lipectomy or open techniques.

PMID- 1352475
TI  - Perineal ectopic testis.

PMID- 1352474
TI  - Evaluation of abnormal biomechanics of the foot and ankle in athletes.
AB  - Athletes often suffer from recurrent or chronic overuse symptoms of the lower
      extremities. During the office visit it is essential to analyse the patient's
      shoes, gait cycle, lower extremities and, especially, the talocrural, subtalar
      and more distal joints of the ankle and foot. The basic (clinical) biomechanical
      analysis can be supplemented by radiographs, treadmill and video analysis and
      mirror table (podoscope) examinations. Ideally, successful pain relief by
      correction of the observed abnormality with an orthotic device completes the
      diagnostic procedure, especially if symptoms return soon after the removal of the
      device. In treatment custom-made, expensive orthotics should not be prescribed
      for overuse symptoms without an obvious malalignment, for asymptomatic athletes
      with a malalignment, or for symptoms in which the causal relationship between the
      biomechanical abnormality and symptoms is difficult to see. Strict indications
      for prescription of orthotics and close cooperation between the attending
      physician, physical therapist and orthotist are prerequisites for obtaining good,
      long-lasting results.

PMID- 1352476
TI  - Orchiopexy: neo-gubernaculum technique.

PMID- 1352477
TI  - The effects of pituitary stalk transection, hypophysectomy and thyroid hormone
      status on insulin-like growth factor 2-, growth hormone releasing hormone-, and
      somatostatin mRNA prevalence in rat brain.
AB  - We have used in situ hybridization histochemistry to determine the effects of
      pituitary stalk transection, hypophysectomy and drug-induced changes in thyroid
      status on mRNA levels encoding insulin-like growth factor 2, somatostatin, and
      growth hormone-releasing factor in the choroid plexus, hypothalamic
      periventricular nucleus, and arcuate nucleus, respectively. Pituitary stalk
      transection and hypophysectomy in Sprague-Dawley rats decreased insulin-like
      growth factor 2 and somatostatin mRNA and increased growth hormone-releasing
      factor mRNA. In each case, the effect of hypophysectomy exceeded that of
      pituitary stalk transection. Treatment with propylthiouracil for 10 days
      decreased somatostatin mRNA, markedly increased growth hormone-releasing factor
      mRNA but had no significant effect on insulin-like growth factor 2 mRNA.
      Treatment with triiodothyronine had no effect on the mRNAs measured. These
      findings corroborate the clinical observation of abnormal somatic growth in
      disturbances of thyroid and growth hormone status and provide further evidence of
      the effects of these metabolic disturbances and of pituitary disconnection and
      hypophysectomy on insulin-like growth factor 2 mRNA prevalence.

PMID- 1352478
TI  - Dopamine-, NMDA- and sigma-receptor antagonists exert differential effects on
      basal and amphetamine-induced changes in neostriatal ascorbate and DOPAC in
      awake, behaving rats.
AB  - Amphetamine and other dopamine agonists elevate the extracellular level of
      neostriatal ascorbate, which has been shown to modulate neuronal function. To
      assess the receptor mechanisms underlying neostriatal ascorbate release, drug
      induced changes in both basal and amphetamine-induced ascorbate release were
      monitored voltammetrically in the neostriatum of freely moving rats. A variety of
      dopamine receptor antagonists decreased basal ascorbate and reversed the increase
      induced by 2.5 mg/kg D-amphetamine. Thus, compared to vehicle treatment,
      administration of classical (haloperidol) and atypical (clozapine) neuroleptics
      or selective D1 (SCH-23390) and D2 (sulpiride) antagonists completely reversed
      the amphetamine-induced rise in ascorbate and also lowered basal levels by 20
      40%. These same effects occurred following injection of dizocilpine (MK-801), a
      non-competitive NMDA antagonist, whereas BMY-14802, a sigma ligand, reversed the
      amphetamine-induced rise without altering basal levels. Simultaneous measurements
      of extracellular DOPAC, a major dopamine metabolite, revealed that haloperidol,
      clozapine, sulpiride and BMY-14802 elevated basal levels and reversed the
      amphetamine-induced decline. Dizocilpine also increased basal DOPAC but failed to
      alter the DOPAC response to amphetamine, whereas both basal and amphetamine
      induced changes in DOPAC were unaffected by SCH-23390. A combination of
      subthreshold doses of SCH-23390 and sulpiride, however, reversed both the
      amphetamine-induced release of ascorbate and the corresponding decline in DOPAC.
      Collectively, these results suggest that whereas dopamine, sigma, and NMDA
      receptors modulate neostriatal ascorbate release, they exert an opposing
      influence on extracellular DOPAC. All drugs attenuated at least some components
      of the amphetamine behavioral response, suggesting a role for multiple mechanisms
      in the behavioral effects of this drug.

PMID- 1352479
TI  - Changes in neurotransmitter parameters in the brain induced by L-cysteine
      injections in the young rat.
AB  - A single subcutaneous injection of L-cysteine (1.2 mg/g body wt.) to 4-day-old
      rats leads to atrophy of the brains examined 27-31 days later. The brains could
      be separated into two groups (type 1 and 2) on account of the degree of atrophy.
      Type-1 lesion, with a brain weight reduction of 20%, was dominated by a severe
      reduction in high-affinity uptake of L-glutamate in CNS regions receiving
      corticofugal fibers such as thalamus and striatum. Glutamate decarboxylase was
      only reduced in cortical structures. In type-2 lesion, with a severe brain
      atrophy of about 50%, high-affinity glutamate uptake was further reduced and
      there was a more pronounced reduction in glutamate decarboxylase activity in
      several brain regions. Cholinergic neurons were less affected by the lesion and
      the levels of choline acetyltransferase showed a relative increase in brain
      regions which partly compensated for their reduction in size.

PMID- 1352480
TI  - Cell proliferative activity in adenomatous hyperplasia of the liver and small
      hepatocellular carcinoma. An immunohistochemical study demonstrating
      proliferating cell nuclear antigen.
AB  - BACKGROUND: Recently, adenomatous hyperplasia (AH) of the liver, a sizable
      parenchymal nodule in the cirrhotic liver, has been considered a preneoplastic
      lesion in human hepatocarcinogenesis. METHODS: The authors evaluated cell
      proliferative activity by immunostaining for proliferating cell nuclear antigen
      (PCNA) in AH (n = 30), small hepatocellular carcinoma (HCC) (n = 14), and their
      surrounding regenerative nodules (SRN). RESULTS: AH was categorized
      histologically as ordinary or atypical. Ordinary AH (n = 8) had no hepatocellular
      atypia, whereas atypical AH (n = 22) was composed of atypical hepatocytes that
      were equivocal as to benignity and malignancy. Three atypical AH contained overt
      malignant foci. The PCNA labeling index of ordinary AH was lower than that of SRN
      and the index of atypical AH was higher than that of SRN except in two cases. The
      PCNA labeling index of malignant foci within atypical AH was higher than that of
      nonmalignant areas of atypical AH and was similar to that of small HCC. For small
      HCC, the PCNA labeling index was much higher than that of SRN and correlated with
      small HCC grades. CONCLUSIONS: These data suggest that ordinary AH is a largely
      developed regenerative nodule with little proliferative activity and that it is
      not a preneoplastic lesion; the data also indicate that atypical AH has much
      proliferative activity, from which malignant foci with greater proliferative
      activity emerge. Atypical AH with or without malignant foci may represent an
      early stage of multi-step hepatocarcinogenesis in humans.

PMID- 1352481
TI  - Transcriptional attenuation following cAMP induction requires PP-1-mediated
      dephosphorylation of CREB.
AB  - We have examined the mechanism by which the transcriptional activity of the cAMP
      responsive factor CREB is attenuated following induction with forskolin.
      Metabolic labeling studies reveal that, after an initial burst of phosphorylation
      in response to cAMP, CREB is dephosphorylated and transcription of the cAMP
      responsive somatostatin gene is correspondingly reduced. The phosphatase
      inhibitor 1 protein and okadaic acid both prevented the dephosphorylation of CREB
      at Ser-133 in PC12 cells and also augmented the transcriptional response to cAMP.
      Of the four Ser/Thr phosphatases described to date, only PP-1 appears to be
      similarly inhibited by these agents. As PP-1 specifically dephosphorylates CREB
      at Ser-133 and inhibits cAMP-dependent transcription, we propose that this
      phosphatase is the major regulator of CREB activity in cAMP-responsive cells.

PMID- 1352482
TI  - The effect of anti-adhesion molecule antibody on the development of collagen
      induced arthritis.
AB  - In order to study how inflammatory cells including autoimmune lymphocytes
      interact with each other to develop collagen-induced arthritis (CIA), we injected
      monoclonal antibodies against mouse LFA-1 and ICAM-1 into DBA/1 mice immunized
      with type II collagen (CII). Both antibodies suppressed the development of CIA.
      These antibodies showed no effect on anti-CII antibody response, although they
      both significantly suppressed DTH response. It was suggested that anti-adhesion
      molecule antibodies suppress CIA mainly through their effect on cell-mediated
      immunity, without affecting humoral immunity under the conditions used.

PMID- 1352483
TI  - Regulation of human cytolytic lymphocyte responses by interleukin-12.
AB  - IL-12 is a heterodimeric cytokine which has been shown to cause the proliferation
      of activated T and NK cells, to enhance the lytic activity of NK cells, and to
      induce IFN-gamma production by resting and activated T and NK cells. We
      previously reported that IL-12 could synergize with IL-2 to activate human LAK
      cells in the presence of hydrocortisone but that IL-12 alone was inactive. We
      herein show that in the absence of hydrocortisone, IL-12 by itself can activate
      human LAK cells. IL-12-induced LAK cell activity was mediated predominantly by
      CD56+ lymphocytes. Activation of LAK cells by IL-12 appeared to be independent of
      IL-2 since it was not inhibited by neutralizing anti-human IL-2. However, IL-12-
      and IL-2-induced LAK cell activation could be partially inhibited by anti-human
      TNF-alpha. Moreover, IL-12 produced in situ appeared to play a role in IL-2
      induced LAK cell activation since rat monoclonal antibodies to human IL-12 could
      partially inhibit the generation of LAK cells in response to IL-2. In addition to
      its effects on LAK cell responses, IL-12 could facilitate specific allogeneic
      human CTL responses. However, IL-12-facilitated CTL responses were blocked by
      neutralizing anti-human IL-2 indicating a requirement for IL-2 produced in situ.
      The ability of IL-12 to facilitate both nonspecific LAK and specific CTL
      responses suggests that it may be useful as a therapeutic agent against some
      tumors and infectious diseases.

PMID- 1352486
TI  - 36th Annual Conference of the Canadian Society of Clinical Chemists. Toronto,
      Canada, May 24-28, 1992. Abstracts.

PMID- 1352485
TI  - Radioisotopic assay of aspartate and alanine aminotransferase.
AB  - The activities of aspartate and alanine aminotransferases in biological samples
      were assessed through a novel and sensitive procedure, based on the conversion of
      [U-14C]2-ketoglutarate to L-[U-14C]glutamate. In human plasma, the generation of
      L-[U-14C]glutamate was proportional to the volume of plasma (20-60 microL) and to
      the length of incubation (30-90 min). The reaction velocity was related to the
      temperature with a Q10 close to 1.7 for aspartate aminotransferase and 2.0 for
      alanine aminotransferase. At 37 degrees C, the 95% confidence interval in healthy
      subjects ranged from 5.1-18.8 U/mL (mean value 11.9 U/L) for aspartate
      aminotransferase and from zero to 20.1 U/L (mean value 9.9 U/L) for alanine
      aminotransferase. The intra-assay coefficient of variation did not exceed 2.5%.
      The present method was also applied to homogenates prepared from rat pancreatic
      islets, liver, heart, parotid glands, and erythrocytes, using no more than 40
      micrograms wet weight of tissue per sample, and could thus be used in small
      biological samples, such as those obtained by needle biopsy.

PMID- 1352484
TI  - IL-3 dependence of a Thy-1lo, B220+, IL-3 receptor-positive antigen-specific DTH
      initiating clone.
AB  - The elicitation of delayed-type hypersensitivity (DTH) reactions in mice is due
      to the sequential action of two different antigen-specific Thy-1+ cells. We have
      previously cloned the early-acting DTH-initiating cell from nude mice that were
      immunized and boosted by contact sensitization with oxazolone (OX). This clone WP
      3.27 produces an antigen-specific factor, OX-F, that acts in an Ag-specific
      manner to initiate DTH. The clone was phenotyped as a Thy-1+, B220+, CD3-, CD4-,
      CD8- cell. In this report, we further detail the characteristics of this unusual
      Ag-specific DTH-initiating cell clone. By flow cytometry analysis, WP-3.27 is Thy
      1lo, Lyt-1+ (CD5+), but CD3-, TCR-alpha beta-, and TCR-gamma delta-. Moreover, WP
      3.27 does not express surface immunoglobulins but expresses B220 (CD45RA), and
      also some macrophage markers such as Mac-1, F4-80, and MHC class II after gamma
      IFN treatment. Interestingly, this clone also expresses IL-3 receptors (IL-3R)
      and not IL-2R. In addition to the Ag-specific DTH-initiating factor, WP-3.27
      constitutively produces IL-3. Inhibition of proliferation of WP-3.27 with an anti
      mouse IL-3 monoclonal antibody suggests that the clone WP-3.27 is IL-3-dependent,
      at least partially. WP-3.27 also constitutively produces IL-1 and IL-6, but not
      TNF-alpha. LPS activation of the clone resulted in a net increase of IL-1, IL-6,
      and TNF-alpha production. Thus, this Ag-specific DTH-initiating cell clone makes
      a unique set of cytokines. Northern blot analysis demonstrated that clone WP-3.27
      transcribes mRNA encoding IL-1, IL-3, IL-6, and TNF-alpha, but not for TNF-beta
      (lymphotoxin). The nature of this unusual cell, which displays characteristics of
      more than one cell lineage, is discussed.

PMID- 1352487
TI  - Pharmacological evaluation of two novel analogues of mianserin: 2-N
      carboxamidinonormianserin (FCC5) and 2-N-carboxamidonormianserin (FCC13).
AB  - 1. The pharmacological properties have been examined of FCC5 (2-N
      carboxamidinonormianserin) and FCC13 (2-N-carboxamidonormianserin), two novel
      analogues of mianserin. 2. FCC5 or FCC13 (100 micrograms/kg, i.v.) caused long
      lasting (greater than 1 h) abolition of 5-hydroxytryptamine (5-HT) and histamine
      induced bronchoconstriction in the anaesthetized guinea-pig. Both analogues had
      no effect (up to 1 mg/kg, i.v.) on bronchoconstriction caused by acetylcholine
      (25-50 micrograms/kg, i.v.). 3. The pressor effects of 5-HT in pithed rats were
      significantly attenuated by FCC5 (0.1 mg/kg, i.v.) or FCC13 (0.5 mg/kg, i.v.). 4.
      Oedema in the rat hind paw caused by intraplantar 5-HT was inhibited by FCC5
      (ID50 0.76 mg/kg, i.p.; 2.7 mg/kg, p.o.) or FCC13 (ID50 0.65 mg/kg, i.p.; 5.8
      mg/kg, p.o.). 5. In the central nervous system (CNS), FCC13 caused antagonism of
      5-HT activity. It inhibited: (i) L-5-hydroxytryptophan (L-5-HTP)-induced head
      twitches in mice (ID50 1.85 mg/kg, i.p.), (ii) fenfluramine-induced facilitation
      of flexor reflex activity (FRA) in spinalized decerebrate rats (SDR) (IC50 0.57
      mg/kg, i.p.). 6. FCC5 (less than or equal to 30 mg/kg, i.p. and less than or
      equal to 3 mg/kg, i.p., respectively) had no effect in either test. In contrast
      to mianserin, it also had no overt central actions as (less than or equal to 30
      mg/kg, i.p.) had no effect on: (i) morphine-induced catalepsy (MIC) or (ii)
      clonidine-induced facilitation of FRA in SDR. However, high doses of FCC13
      inhibited MIC (ID50 20 mg/kg, i.p.), but had no effect on (ii) (less than or
      equal to 10 mg/kg, i.p.). 7. Thus, FCC5 and FCC13 are potent, orally active H1
      and 5-HT receptor antagonists. However, in contrast to FCC13 and mianserin, FCC5
      did not cause CNS-mediated effects.

PMID- 1352488
TI  - Autacoids affecting vascular tone in the human fetal extracorporeal circulation.
AB  - 1. The human fetal extracorporeal circulation is normally a vasodilated, low
      pressure system. 2. As this vasculature lacks innervation, autacoids have been
      postulated as being of great importance in controlling its tone. 3. This has now
      been confirmed by pharmacological in vitro techniques, particularly utilizing
      perfusion of the isolated umbilical cord and placental lobule. 4. The fetal
      umbilical-placental vessels are sensitive to a wide range of vasoconstrictor
      autacoids, some of which can cause intense vasospasm. 5. Thromboxane A2 receptors
      have been identified in both umbilical vein and placental villous vessels. 6.
      Prostacyclin and endothelial cell-derived relaxing factor (or nitric oxide) may
      be largely responsible for the low vascular resistance normally found in the
      fetal extracorporeal circulation. 7. Immediately after birth it is likely that
      stimuli such as cooling, stretching and handling of the umbilical cord cause
      release of eicosanoids and other autacoids from the vessels, leading to their
      complete closure.

PMID- 1352489
TI  - Evolution of phenotypic memory T cells in HIV-1 infected infants and children.
AB  - Infants are reported to be devoid of memory T cells at birth but acquired them
      with time. A cross-sectional study of peripheral blood mononuclear cells from HIV
      infected and uninfected infants and children that bear the CD4R0 antigen was
      undertaken to describe the development of memory T cells. Linear regression lines
      derived from the data revealed increasing percentages of memory CD4 and CD8 cells
      in the uninfected children. Memory CD4 cells in the infected children were
      detected at a frequency equal to or greater than that seen in uninfected children
      until 6 months of age but subsequently declined with age. In contrast, memory CD8
      cells were found to be significantly increased in HIV-infected children early in
      life with a rate of increase similar to that seen in the uninfected population.
      This increase in memory CD8 cells may facilitate the early diagnosis of HIV
      infection.

PMID- 1352490
TI  - 1st International Workshop on Hypertrophic Osteoarthropathy. Florence, Italy,
      June 21-24, 1992.

PMID- 1352491
TI  - Lung mechanics and oxygen consumption during spontaneous ventilation and severe
      heart failure.
AB  - The effects of acute heart failure on lung mechanics and oxygen consumption (VO2)
      during normocarbic spontaneous ventilation were studied in 21 anesthetized pigs.
      Heart failure severe enough to double oxygen extraction (O2ex) was induced with
      intravenous esmolol boluses and infusion. Compared to normal, the inspiratory
      elastic work of breathing (Wel) increased from 335 +/- 371 (mean +/- SD) to 559
      +/- 48 mm Hg.ml (p less than 0.003) during heart failure, lung compliance (CL)
      fell from 121 +/- 144 to 22 +/- 15 ml/mm Hg (p less than 0.05), and respiratory
      power climbed from 140 +/- 200 to 245 +/- 214 mm Hg.ml.min-1 (p less than 0.002).
      These mechanical changes were accompanied by a decrease in both VO2 (221 +/- 61
      to 191 +/- 50 mlO2/min, p less than 0.05) and oxygen delivery (DO2) (680 +/- 240
      to 260 +/- 90 mlO2/min, p less than 0.004). The VO2/DO2 ratio doubled (p less
      than 0.0002), confirming increased O2ex. In conclusion, severe acute heart
      failure decreased CL, and increased Wel and respiratory power significantly. The
      depressed cardiac output limits both DO2, and to some extent, VO2. However, a
      greater proportion of the delivered O2 is consumed, supplying indirect evidence
      which suggests that the respiratory muscles' VO2 increases as a consequence of
      increased power expenditure.

PMID- 1352492
TI  - Bronchiolitis obliterans associated with polyarteritis nodosa.
AB  - Bronchiolitis obliterans with organizing pneumonia (BOOP) has not previously been
      described in association with polyarteritis nodosa (PAN). This report describes a
      patient in whom fulminant systemic PAN followed subacute onset of BOOP, with
      associated pulmonary arteritis.

PMID- 1352493
TI  - [What significance does the obstructive sleep apnea syndrome have postoperatively
      or in the intensive care unit?].

PMID- 1352495
TI  - [Phototoxicity--photoallergy].

PMID- 1352494
TI  - [Liver damage from organic solvents].

PMID- 1352496
TI  - Comparison of casual, ambulatory and self-measured blood pressure in a study of
      nitrendipine vs bisoprolol.
AB  - In a double-blind, placebo-controlled study the antihypertensive efficacy and
      tolerability of a single morning dose of either 10 mg bisoprolol (n = 26) or 20
      mg nitrendipine (n = 27) were investigated. Blood pressure was measured by three
      techniques: (1) Casual blood pressure 24 h after the dose; (2) ambulatory 24-h
      whole-day monitoring; and (3) self-recorded blood pressure in the morning 24 h
      after the dose (6-8 a.m.) and in the evening (6-8 p.m.). After 4 weeks of therapy
      bisoprolol had produced a highly significant reduction in blood pressure as
      assessed by causal, ambulatory day- and night-time monitoring, and self-measured
      morning and evening readings. Bisoprolol was significantly more effective than
      nitrendipine, which did not induce a significant reduction in the ambulatory
      night-time recordings. Whole-day ambulatory blood pressure profiles showed an
      antihypertensive effect of bisoprolol throughout the entire 24-h period. 24-h
      blood pressure curves after nitrendipine demonstrated a markedly shorter duration
      of action, with no reduction in early morning blood pressure. Adverse effects and
      tolerability of the two drugs were comparable. The average changes in systolic
      and diastolic blood pressure after bisoprolol and nitrendipine in 2-h periods of
      ambulatory monitoring (6-8 a.m. and 6-8 p.m.) and self-measured blood pressure (6
      8 a.m. and 6-8 p.m.) showed a good agreement between ambulatory and self-measured
      blood pressure determinations with no significant difference between the methods.
      The results show that 24 h antihypertensive efficacy was more pronounced for
      bisoprolol than for nitrendipine at the doses studied.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1352497
TI  - Does treatment with beta-adrenergic blocking agents cause a decrease in beta 2
      adrenoceptor affinity?
AB  - The effect of beta-adrenoceptor antagonists (BAAs) differing in lipophilicity and
      partial agonist activity (PAA), and a full agonist, on the dissociation constant
      for [125I]-(-)- iodocyanopindolol binding to beta 2-adrenoceptors (KD) has been
      investigated. Twelve healthy, normotensive male volunteers (mean age 22.3 y) were
      treated with different BAAs according to a cross-over design. The drugs used were
      propranolol (highly lipophilic BAA, no PAA), pindolol (moderately lipophilic BAA,
      strong PAA), dilevalol (highly lipophilic BAA, weak PAA) and salbutamol (full
      agonist). Before and after a single dose and an 8 day course of one of the drugs,
      blood pressure and the beta 2-adrenoceptor characteristics of mononuclear
      leukocytes (MNL) were determined. Between the treatment periods, there was a
      washout interval of 14 days. All BAAs decreased the blood pressure, but only
      propranolol lowered heart rate. Treatment with salbutamol decreased the diastolic
      and increased the systolic blood pressure and heart rate. Three hours after the
      single dose of any of the BAAs, a more than 2-fold increase in KD was observed,
      and the increase became larger after 8 days of administration (up to 3.7-fold
      increase). In contrast, no effect on KD was observed after treatment with
      salbutamol. BAAs with PAA and salbutamol induced a 30% decrease in beta 2
      adrenoceptor density. It is concluded that treatment with BAAs, irrespective
      their lipophilicity or PAA, induces a decrease in the affinity of MNL beta 2
      adrenoceptors for antagonists. This phenomenon may help to explain the
      contradictory relationship between the kinetics and dynamics of BAAs.

PMID- 1352498
TI  - Minimal growth requirements of mature T lymphocytes: interleukin (IL)-1 and IL-6
      increase growth rate but not plating efficiency of CD4 cells stimulated with anti
      CD3 and IL-2.
AB  - We show that interleukin (IL)-2 is necessary and sufficient for the proliferation
      of both CD4 and CD8 subsets of peripheral murine T cells activated by plastic
      bound anti-CD3 monoclonal antibodies (mAb). The frequency of proliferating cells
      (f) was 0.32 for CD4 cells and 0.63 for CD8 cells. These frequencies were not
      increased by the addition of IL-1 or IL-6, alone or in combination. These
      cytokines were unable to induce responsiveness to IL-2 in T cells confirming that
      they cannot substitute for the signal delivered via the TcR/CD3 complex. On the
      other hand, IL-1 and IL-6 increase the growth rate of CD4 cells. The addition of
      IL-6 significantly lowered the mean doubling time (dt) of CD4 cells (dt: 26 h vs.
      38 h in the presence of IL-2 alone, p less than 0.01), while the addition of IL
      1, ineffective by itself, combined with IL-6 further increased the growth rate of
      CD4 cells (dt: 23 h, p less than 0.001). The growth rate of CD8 cells stimulated
      with anti-CD3 and IL-2, was markedly faster than that of CD4 cells (dt: 18 h vs.
      38 h, p less than 0.001) and was not significantly influenced by addition of IL-1
      and/or IL-6.

PMID- 1352499
TI  - Induction of homotypic T cell adhesion by triggering of leukocyte function
      associated antigen-1 alpha (CD11a): differential effects on resting and activated
      T cells.
AB  - The leukocyte integrin LFA-1 (CD11a/CD18) plays a key role in many adhesive
      interactions involving cells of the immune system. Recently, it has been shown
      that LFA-1 is not only involved in cell adhesion, but that stimulation of LFA-1
      can also contribute to cell activation. We now demonstrate that triggering of LFA
      1 on T lymphocytes by monoclonal antibodies (mAb) against the LFA-1 alpha chain,
      but not against the LFA-1 beta chain, promotes cell adhesion. Induction of
      homotypic adhesion was only observed in T cells that had been pre-activated with
      anti-CD3 and not in resting peripheral blood T lymphocytes. The induced homotypic
      adhesion is mediated by LFA-itself, because it was inhibited by anti-LFA-1 beta
      mAb. This notion is supported by the temperature and divalent cation dependence
      which is characteristic of LFA-1-mediated adhesion. mAb against ICAM-1 (CD54) did
      not block LFA-1 alpha-induced adhesion. The sensitivity of LFA-1 alpha-induced
      adhesion to H7, which prevents the activation of protein kinase C and protein
      kinase A, and to cytochalasin B, which inhibits microfilament formation, suggests
      that the activation of the LFA-1 pathway through the LFA-1 alpha chain involves
      cell activation and requires an intact cytoskeleton.

PMID- 1352500
TI  - Four CD45/P56lck-associated phosphorproteins (pp29-pp32) undergo alterations in
      human T cell activation.
AB  - In human T lymphocytes a functional complex is formed between the protein
      tyrosine phosphatase CD45, the protein tyrosine kinase p56lck and a
      phosphoprotein, pp32, a possible common substrate. Here we demonstrate that the
      previously described pp32 protein is composed of two distinct molecules (pp29 and
      pp32) in both resting human T lymphocytes and continuously proliferating T
      lymphoma lines. Importantly, T lymphocyte activation employing CD2 monoclonal
      antibodies (mAb), CD3 mAb or phorbol 12, 13 dibutyrate results in loss of pp29
      and pp32 from the CD45/p56lck molecular complex and concomitant association of
      two distinct phosphoproteins with different molecular weights (pp30 and pp31).
      These events appear to be unrelated to clonal T cell growth but rather depend on
      receptor-mediated differentiation signals. Reprecipitation experiments employing
      an antiserum directed at a consensus sequence of GTP-binding proteins suggest
      that all four pp29-pp32 molecules might represent proteins with GTP-binding
      properties. Biochemical analysis of pp29-pp32 employing V8-protease digestion
      indicates that they differ in low-molecular weight fragments of 8, 5, 4.5, 4 and
      3 kDa, respectively.

PMID- 1352501
TI  - Molecular basis for a severe case of leukocyte adhesion deficiency.
AB  - The leukocyte integrins LFA-1, Mac-1 and p150,95 (CD11a/CD18, CD11b/CD18,
      CD11c/CD18) mediate crucial leukocyte adhesive functions in immune and
      inflammatory reactions. Leukocyte adhesion deficiency (LAD) disease is caused by
      the defective expression of these adhesion molecules on leukocytes, and is
      characterized by recurrent infections and impaired pus formation due to the
      blockade of leukocyte migration into inflamed tissues. LAD is originated by
      heterogeneous mutations affecting the CD18 gene and, based on the severity of the
      deficiency, two phenotypes (severe and moderate) have been defined. Biochemical
      and genetic studies have allowed the classification of five different types of
      LAD. We have identified a type V LAD patient (severe phenotype, and normal size
      and levels of both CD18 precursor and CD18 mRNA), and determined its molecular
      basis. Reverse transcription-polymerase chain reaction and cloning and sequencing
      of CD18 cDNA derived from this patient revealed three silent mutations and a
      missense mutation that leads to the substitution of glycine at position 169 for
      an arginine. Analysis of patient-derived cDNA clones revealed the concomitant
      presence of aberrant splicing within the 5' region of the CD18 gene. The
      description of an identical mutation at residue 169 in an unrelated severe LAD
      patient raises the possibility that severe LAD type V is caused by a unique
      genetic defect.

PMID- 1352502
TI  - Genetic control of nonresponsiveness to hepatitis B virus vaccine by an extended
      HLA haplotype.
AB  - We previously reported evidence for a statistical association between the
      serologically determined HLA-Bw54, DR4 and DRw53 alleles and the non-immune
      responsiveness to hepatitis B virus surface antigen (HBsAg) in the Japanese
      population. To identify the locus and allele within the HLA region associated
      with the nonresponsiveness to HBsAg, serological HLA typing, DNA typing of HLA-DQ
      and DP alleles using amplified HLA genes and sequence-specific oligonucleotide
      probes, and restriction fragment length polymorphism (RFLP) analysis of the
      fourth component of complement (C4) genes were performed in healthy unrelated
      Japanese vaccinees who were immunized subcutaneously three times with plasma
      derived HBsAg vaccine. In nonresponders to HBsAg, the frequencies of HLA-Bw54
      cross-reactive epitope group (CREG); (Bw54, Bw55, Bw56 and other Bw22), C4 RFLP
      (6.5 kb + 12.0 kb), DR4, DRw53 and DQw4 (DQA1*0301-DQB1*0401) were increased and
      the frequencies of HLA-DR1, DRw6 and DQw1 were decreased as compared with those
      in healthy unrelated controls. Further analysis revealed that the coexistence of
      HLA-Bw54CREG and DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) was associated with the
      nonresponder group, whereas, donors positive for exclusively either Bw54 CREG or
      DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) were not associated with the nonresponder
      group. Because there is a strong linkage disequilibrium between HLA-Bw54CREG, C4
      RFLP (6.5 kb + 12.0 kb) and HLA-DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) in the
      Japanese population, the extended HLA-Bw54CREG-C4 RFLP (6.5 kb + 12.0 kb)-DR4-DR
      w53-DQw4 (DQA1*0301-DQB1*0401) haplotype may well control nonimmune
      responsiveness to HBsAg. This extended HLA haplotype controls nonresponsiveness
      as a dominant genetic trait because all ten heterozygotes and two of three
      probable homozygotes of this extended HLA haplotype were nonresponders.

PMID- 1352503
TI  - Non-random features of the repertoire expressed by the members of one V kappa
      gene family and of the V-J recombination.

PMID- 1352504
TI  - Effect of apraclonidine on blood-aqueous barrier permeability to plasma protein
      in man.
AB  - Effect of a single instillation of 30 microliters 0.5% apraclonidine on the
      coefficient of protein entry (k(in)), a quantitative index of blood-aqueous
      barrier permeability, was determined in ten normal volunteers. Before and after
      administering the drug to one eye and the vehicle to the other eye of a subject,
      protein concentrations in the anterior chamber were measured using a laser flare
      cell meter. One week later, aqueous flow rate was determined by fluorophotometry
      under the same experimental conditions. The k(in) was calculated from protein
      concentrations in the anterior chamber and the plasma and from aqueous flow rate
      based on a transfer equation formulating the kinetics of protein molecules in the
      anterior chamber. The k(in) showed a significant reduction at 3 and 4 hr after
      drug administration with a maximum decrease of 21 +/- 6% (mean +/- S.E., n = 10)
      at 3 hr, while the aqueous flow rate showed a significant reduction from 2 to 6
      hr with a maximum decrease of 45 +/- 5% at 3 hr. The results indicated that
      topical apraclonidine reduced both blood-aqueous barrier permeability as well as
      aqueous flow rate in humans. This dual reduction may relate to the efficacy of
      this drug in suppressing the post-laser intraocular pressure rises in patients.

PMID- 1352505
TI  - Quinpirole alters quadruped activity in rats from the second postnatal week.
AB  - The present study shows that the effects of quinpirole (1 mg/kg) during the
      second postnatal week but not before resemble the effect of the drug in adult
      rats in increasing quadruped activity, eliminating grooming, reducing lateral
      bending, and stimulating verticalized turning. Quinpirole also modifies the
      morphology of turning behavior, the primary form of coordinated quadruped
      locomotion in neonate laboratory rat pups. Under saline, turning involves lateral
      bending and straightening of the trunk. Under quinpirole, turning includes a
      vertical component of movement ("verticalized turning") instead of the normal
      lateral bending of the trunk. A similar trend of change in turning is induced by
      quinpirole in adult rats: An acute injection reduces lateral bending, and a
      chronic treatment increases verticalization. The induction of vertical turning in
      the second but not the first postnatal week may stem from the normal course of
      development since typical vertical movements of intact rats (supported rearing
      and wall climbing) develop only by the age of 11-14 postnatal days. Verticalized
      turning may be thus a drug-induced expression of an age-related tendency to
      perform vertical movements.

PMID- 1352506
TI  - [The importance of the early ergometry test after a myocardial infarct in
      patients treated with thrombolysis and beta-blockers].

PMID- 1352507
TI  - [National Congress on Cardiology. XXIII National Congress of the National
      Association of Hospital Cardiologists. Firenze, 7-10 June 1992. Abstracts].

PMID- 1352509
TI  - Correlation of c-erbB-2 with invasion and metastasis in human gastric cancer.

PMID- 1352508
TI  - An experimental study on the gastric acid and gut hormone secretion after pylorus
      preserving duodenectomy in dogs.
AB  - To clarify changes in gastric acid and gut hormone secretion after pylorus
      preserving pancreaticoduodenectomy (PPPD), an experimental study was performed
      using a model of pylorus-preserving duodenectomy in dogs previously provided with
      Heidenhain pouch (HP). The duodenectomy involves resection of the duodenum and 10
      cm of the proximal jejunum preserving 2 cm of juxtapyloric duodenum and round
      shaped duodenal wall around pancreatic papilla. Reconstruction was done by
      anastomosing the rho-shaped jejunal loop to gallbladder, juxtapyloric duodenum
      and peripapillar round-shaped duodenal wall with ligation of the common bile
      duct. For these dogs, intravenous glucose tolerance test (IVGTT), oral glucose
      tolerance test (OGTT), meal ingestion test (TM) and histological studies of
      pancreatic specimen obtained at autopsy were performed investigating pancreatic,
      gastric acid and gut hormone secretion. Preservation of endocrine and exocrine
      pancreatic secretion after operation demonstrated our experimental model to be
      adequate for evaluation of the factor of duodenectomy in PPPD on gastric acid and
      gut hormone secretion avoiding the influences of changes in pancreatic secretion.
      Postprandial gastric acid secretion from HP did not change significantly after
      operation. Postprandial secretion of gastrin, glucagon, GIP and enteroglucagon
      did not alter significantly after operation. These results indicated that in the
      clinical PPPD procedure, preservation of more than 2 cm of duodenum from the
      pylorus produced neither postprandial gastric acid hypersecretion, which might be
      cause of postoperative stomal ulcer, nor any change of related gut hormone
      secretion.

PMID- 1352510
TI  - HLA-DQA1 DNA typing in patients with duodenal ulcer by the PCR-RFLP method.

PMID- 1352511
TI  - Effects of converting enzyme inhibition and alpha receptor blockade on the
      angiotensin pressor response in the American alligator.
AB  - This study examines the effects of two converting enzyme inhibitors (captopril
      and enalaprilat) and two alpha-adrenergic receptor antagonists (phentolamine and
      phenoxybenzamine) on the pressor response produced by exogenous angiotensin I
      ([Asp1, Val5, Ser9] ANG I, fowl) and [Val5] angiotensin II (ANG II) in the
      American alligator (Alligator mississippiensis). Bolus administration of ANG I at
      0.1, 0.5, and 1.0 micrograms/kg; ANG II at 0.05, 0.1, and 0.5 micrograms/kg; or
      norepinephrine (NE) at 2 micrograms/kg elicited dose-dependent increases in
      arterial blood pressure. Captopril (0.5 mg/kg/hr) and enalaprilat (300
      micrograms/kg/hr) significantly reduced the response to ANG I, but not ANG II or
      NE. Both phenoxybenzamine (0.25 mg/kg/min) and phentolamine (1 mg/kg/hr)
      effectively blocked the NE pressor response (84 and 88%, respectively) and
      attenuated (42-80%) the pressor effects of ANG I and ANG II. These results
      support previous work suggesting the alligator may possess a renin-angiotensin
      system with characteristics similar to those found in mammals and other
      vertebrates. In addition, the pressor response to exogenously administered ANG I
      and ANG II was attenuated by alpha adrenergic receptor blockade and thus may be
      due, in part, to secondary catecholamine release.

PMID- 1352512
TI  - Modular design of the Enterococcus hirae muramidase-2 and Streptococcus faecalis
      autolysin.
AB  - The mature forms of the extracellular muramidase-2 of Enterococcus hirae and
      Streptococcus faecalis autolysin have very similar primary structures. Each
      consists of an active-site-containing N-terminal domain fused to a multiple
      repeat C-terminal domain. Polypeptide segments occurring at equivalent places in
      these two bacterial wall lytic enzymes have homologues in two phage lysozymes and
      in three functionally unrelated proteins, illustrating the principle that protein
      molecules frequently are constructed from modules that are linked in a single
      polypeptide chain.

PMID- 1352513
TI  - Genetic variation between strains of the Mediterranean fruit fly, Ceratitis
      capitata, detected by DNA fingerprinting.
AB  - DNA fingerprinting has been used to detect genetic variation in the Mediterranean
      fruit fly, Ceratitis capitata. Three different probes have been identified that
      can be used to detect DNA restriction fragment length polymorphisms between
      strains of this species. The strains used in this study differ only in terms of
      their geographic origin or genetic background. One of the probes used is the
      bacteriophage vector M13, and the other two are repetitive sequences derived from
      the medfly genome based on a weak homology to M13. Within a strain, each probe
      produces a consistent restriction fragment profile that is not affected by the
      method or timing of DNA extraction. Between strains, when M13 is used as a probe,
      an average of 10% of the observable bands are polymorphic. Use of the medfly
      genomic sequences as a probe increases the proportion of polymorphic bands
      between strains up to 30%. The fact that genetic differences between even such
      closely related strains can be reliably detected by this method holds great
      promise for studies of insect pests including the ability to monitor the
      movements of pest species, determining the extent of genetic variation in pest
      populations, and in making identifications from otherwise unidentifiable
      material.

PMID- 1352514
TI  - Vitamin A deficiency and colonic electrogenic absorption and secretion in the
      rat.
AB  - The effects of vitamin A deficiency on electrogenic transport in the colon were
      examined in rats made vitamin A deficient at weaning by feeding a vitamin A
      deficient diet for 40 days. A pair fed control group was given the same diet but
      supplemented with soluble vitamin A in their drinking water. The basal and
      stimulated electrogenic secretory and absorptive functions of the muscle stripped
      proximal, mid, and distal colon were examined in vitro using the short circuit
      current (Isc) as the index of net ion transport. A significant increase in the
      basal and secretory Isc (mainly Cl-ions) induced by the cholinergic agonist
      bethanechol was observed in the mid-colon of the vitamin A deficient rats. In the
      distal colon, however, vitamin A deficiency caused a significant reduction in
      both the basal and secretory Isc response to bethanechol compared with the
      vitamin A supplemented pair fed control. Secretory Isc induced by dibutyryl
      cyclic adenosine monophosphate was not significantly altered by vitamin A
      deficiency. The condition abolished the response of the distal colon to luminal
      amiloride (0.1 mmol/l). Thyroid hormone induced reduction in the distal colonic
      response to aldosterone is implicated in this lack of response. This is the first
      experimental linkage between vitamin A action, the thyroid hormone and
      aldosterone on colonic function. The colonic changes induced by vitamin A
      deficiency, namely hypersecretion and a reduced electrogenic distal absorptive
      function, together with the previously described small intestine hypersecretion
      may be the underlying basis for the diarrhoea observed in human and animal
      vitamin A deficiency.

PMID- 1352515
TI  - Mechanism of action of an antifungal antibiotic, RI-331, (S) 2-amino-4-oxo-5
      hydroxypentanoic acid; kinetics of inactivation of homoserine dehydrogenase from
      Saccharomyces cerevisiae.
AB  - An antifungal antibiotic (S) 2-amino-4-oxo-5-hydroxypentanoic acid, inhibited the
      biosynthesis of the aspartate family of amino acids (methionine, isoleucine and
      threonine) followed by the inhibition of protein biosynthesis in Saccharomyces
      cerevisiae. This inhibition was effected by impeding the biosynthesis of their
      common intermediate precursor, homoserine. The inhibition of biosynthesis of
      homoserine by the antibiotic was attributable to inactivation of homoserine
      dehydrogenase [EC 1.1.1.3], which is involved in the conversion of aspartate
      semialdehyde to homoserine in the metabolic pathway leading to threonine,
      methionine and isoleucine. Since such enzymic activity is not present in animal
      cells, the selective antifungal activity of the antibiotic is thus explained.

PMID- 1352517
TI  - International Neuropsychological Society, 14th European Conference. Durham,
      England, July 8-11, 1992. Abstracts.

PMID- 1352518
TI  - DNA polymorphisms in strains of Mycobacterium tuberculosis analyzed by pulsed
      field gel electrophoresis: a tool for epidemiology.
AB  - Mycobacterium tuberculosis isolates were studied by comparing large restriction
      fragment (LRF) patterns produced by digestion of chromosomal DNA with infrequent
      cutting endonucleases and pulsed-field gel electrophoresis. Four cultures of
      H37Rv and 36 clinical isolates of M. tuberculosis were compared by using DraI,
      AsnI, XbaI, and SpeI. DraI and AsnI allowed easy visual separation of 18 of 21
      epidemiologically unrelated strains. XbaI and SpeI allowed discrimination of all
      21 unrelated strains, including the 3 strains inseparable with DraI and AsnI, but
      comparison of LRF patterns was more tedious because of overlapping fragments. A
      total of 26 isolates belonging to 10 clusters of related isolates were compared
      by pulsed-field gel electrophoresis, with all related isolates giving identical
      LRF patterns. These included multiple isolates from the same patient or the same
      family. The same grouping of clustered isolates was obtained when BamHI DNA
      digests were hybridized with two probes from the insertion sequence IS6110. Long
      term laboratory passage of H37Rv produced minimal detectable changes in LRF
      patterns. LRF patterns are useful tools for epidemiologic studies of tuberculosis
      without the need for radioactive or specific DNA probes.

PMID- 1352519
TI  - Use of pulsed-field gel electrophoresis for investigation of hospital outbreaks
      of Acinetobacter baumannii.
AB  - Genomic DNAs from taxonomically and epidemiologically well-defined strains of
      Acinetobacter baumannii were digested with restriction endonucleases that cleave
      with low frequency, and the fragments were separated by pulse-field gel
      electrophoresis. Restriction fragment length polymorphisms were observed.
      Restriction fragment length polymorphism analysis can be used as an
      epidemiological tool to delineate outbreaks of nosocomial infections caused by A.
      baumannii.

PMID- 1352516
TI  - Characterization of Escherichia coli glnL mutations affecting nitrogen
      regulation.
AB  - Nitrogen regulator II (NRII), the product of the Escherichia coli glnL (ntrB)
      gene, regulates the activation of transcription of glnA and the Ntr regulon by
      catalyzing the phosphorylation and dephosphorylation of the transcription factor
      NRI. Previous results have indicated that under conditions of nitrogen excess,
      transcriptional activation is prevented by an NRI-phosphate phosphatase activity
      that is observed when NRII and another signal transduction protein known as PII
      (the glnB product) interact. The availability of PII for this interaction is
      controlled by a uridylytransferase/uridylyl-removing enzyme, encoded by glnD,
      that reversibly modifies PII in response to intracellular signals of nitrogen
      availability. Here we describe the isolation and characterization of missense
      mutations in glnL that suppress the Ntr- phenotype resulting from a leaky glnD
      mutation. The regulation of glnA expression in the pseudorevertants was found to
      vary from complete insensitivity to ammonia in some strains (GlnC phenotype) to
      nearly normal regulation by ammonia in other strains. Sequence analysis indicated
      that in 16 instances suppression was due to point mutations at 14 different
      sites; 10 different mutations resulting in a variety of phenotypes were
      identified in a cluster extending from codons 111 to 154 flanking the site of
      NRII autophosphorylation at His-139. Complementation experiments with multicopy
      plasmids encoding NRII or PII showed that suppression by GlnC glnL alleles was
      eliminated upon introduction of the plasmid encoding NRII but was not affected by
      introduction of the plasmid encoding PII. Conversely, suppression by certain glnL
      alleles that resulted in regulated expression of glnA was eliminated upon
      introduction of either the plasmid encoding NRII or that encoding PII. We
      hypothesize that mutants of the latter type result in a subtle perturbation of
      the NRII-PII interaction and suggest two possible mechanisms for their effects.

PMID- 1352520
TI  - Cerebrospinal fluid neuropeptides in mood disorder and dementia.
AB  - Cerebrospinal fluid (CSF) concentrations of immunoreactive corticotropin
      releasing hormone (CRH) and somatostatin (SRIF) were measured in female
      psychiatric inpatients with DSM-III-R diagnoses of major depression, mania,
      generalized anxiety and somatization disorder. In addition, elderly patients with
      dementia disorders, with or without concomitant major depression, were also
      investigated. CSF SRIF was not significantly different among these groups; on the
      other hand, mean CSF CRH concentrations were significantly higher in major
      depression and in dementia with depression as compared with neurological controls
      with no psychiatric disorders. CSF CRH levels in mania, simple dementia, or
      anxiety or somatization disorder were not significantly different from the
      controls. Background physical or clinical variables did not account for the
      differences in CRH concentrations. It is concluded that CSF CRH elevation may be
      present in some patients with major depression independent of age and an
      underlying dementia disorder.

PMID- 1352521
TI  - Zotepine in the treatment of schizophrenic patients with prevailingly negative
      symptoms. A double-blind trial vs. haloperidol.
AB  - Zotepine, a neuroleptic agent with additional 5-HT2 blocking properties, was
      compared with haloperidol in the treatment of schizophrenic patients with
      predominantly negative symptoms using a double-blind design. During the
      investigation period zotepine treated patients showed significant improvements in
      all rating instruments whereas haloperidol treated patients did not. Patients in
      the zotepine group developed fewer clinical side effects. The results of the
      presented study confirm the positive impressions gained in earlier open trials
      with zotepine.

PMID- 1352522
TI  - Instability of the minisatellite sequence in the first intron of the rat renin
      gene and localization of the gene to chromosome 13q13 between FH and PEPC loci.
AB  - A minisatellite sequence in the first intron of the rat renin gene showed five
      allelic polymorphism in 11 inbred rat strains. A new allelic variant, which was
      thought to be generated in the germ line, was observed in 136 animals of two sets
      of backcross progenies originating from parental strains with different alleles.
      These facts suggested that the minisatellite is genetically unstable. A linkage
      analysis using the backcross progenies confirmed the assignment of renin locus
      (REN) on linkage group (LG) X at a site between FH (fumarate hydratase) and PEPC
      (peptidase) loci. Fluorescence in situ hybridization allowed mapping of the renin
      gene on rat chromosome 13q13.

PMID- 1352523
TI  - The mtDNA genealogy of closely related Drosophila silvestris.
AB  - Genetic, morphological, and behavioral analyses have been used to examine the
      evolutionary dynamics and phylogeny of the rare Hawaiian Drosophila species, D.
      silvestris. Critical to understanding the evolution of this species is the
      examination of the distribution of populations of D. silvestris on the Big Island
      of Hawaii. Behavioral analysis using mating asymmetries and the Kaneshiro
      hypothesis as an indicator of ancestral behavioral state has suggested that flies
      from the northern part of the island are ancestral to those on the southern part
      of the island. Consequently, a sequential pattern of colonization going from
      north to south is predicted for these flies on the east side of the Island of
      Hawaii. We have examined this prediction using mitochondrial DNA (mtDNA)
      restriction site analysis with four-base cutters and DNA sequencing. The
      resulting mtDNA phylogeny based on 23 phylogenetically informative restriction
      sites and two phylogenetically informative DNA sequence characters agrees in part
      with the phylogeny predicted from the behavioral data.

PMID- 1352524
TI  - A program for the estimation of restriction endonuclease site positions from
      restriction fragment size and number: an aid for mitochondrial DNA analysis.

PMID- 1352525
TI  - Thymocyte costimulating antigen is CD26 (dipeptidyl-peptidase IV). Costimulation
      of granulocyte, macrophage, and T lineage cell proliferation via CD26.
AB  - The rat thymocyte costimulating protein appears to be involved in the regulation
      of CD4-/CD8- thymocyte proliferation in vitro. We show that thymocyte
      costimulating protein is dipeptidyl peptidase IV (E.C.N.3.4.14.5) also known as
      CD26. Some bone marrow cells as well as CD4-/CD8- and, and to a lesser extent,
      more differentiated T cells respond by proliferating to a CD26 specific mAb
      mediated costimulus that does not influence dipeptidyl dipeptidase IV enzyme
      activity. This suggests the existence of a CD26-linked regulatory mechanism of
      proliferation that is operational on granulocyte- and macrophage-lineage cells
      and throughout T cell development.

PMID- 1352526
TI  - Contributions of the CD2 and CD28 T lymphocyte activation pathways to the
      regulation of the expression of the colony-stimulating factor (CSF-1) gene.
AB  - The T cell adhesion molecule CD28 provides a costimulatory signal, in combination
      with either CD2 or CD3 mAb. CD28 appears to regulate the expression, by T cells,
      of cytokines normally produced by accessory cells, namely IL-1 alpha, TNF-alpha,
      and CSF-1. The CSF-1 gene is expressed as a 4.0-kb transcript by human T cells
      activated with mAb directed against CD2 and CD28, alone or in combination. A
      kinetic analysis of its expression showed low steady-state levels of the
      transcript after CD2 stimulation, and a transient rise after CD28 stimulation. In
      contrast, a mean fivefold increase in the levels of the transcript was detected
      in CD2 plus CD28-stimulated cells. The potential mechanisms regulating this
      increase were investigated. The half-life of the CSF-1 transcript was identical
      in cells activated with either CD28 or CD2 plus CD28. Transcription of the CSF-1
      gene appeared to undergo attenuation in resting cells as well as in cells
      activated via a single pathway; this attenuation was relieved in part by the
      combined CD2 plus CD28 stimulation. Thus in vitro costimulation via the CD2 and
      CD28 molecules regulates the expression of the CSF-1 gene mainly at the
      transcriptional level.

PMID- 1352527
TI  - Lymphocyte adhesion mediated by lymphocyte function-associated antigen-1. I. Long
      term augmentation by transient increases in intracellular cAMP.
AB  - Lymphocyte adhesion to target cells is mediated, in part, by the interaction of
      lymphocyte function-associated Ag-1 (LFA-1) with intercellular adhesion molecule
      1 (ICAM-1). Cells of the B cell line, JY, express both coreceptors and have been
      used as a model for intercellular adhesion mediated by these molecules. Elevation
      of the intracellular cAMP concentration ([cAMP]i), by any of several reagents,
      for periods as brief as 30 min, led to enhanced intercellular adhesion in a
      concentration dependent manner 5 to 8 h later. Two protein kinase A inhibitors,
      KT5720 and H-89, but not the protein kinase C inhibitor calphostin C, blocked the
      effects of elevated [cAMP]i. These data suggest a role for protein kinase A in
      this response. The adhesion augmented by increased [cAMP]i was due to LFA-1/ICAM
      1 interactions between cells because it was blocked by either anti-LFA-1 or anti
      ICAM-1 mAb. Elevated [cAMP]i induced cell surface patching of LFA-1, but not ICAM
      1, and this redistribution preceded intercellular adhesion. Finally,
      redistribution of LFA-1 was not mediated by the cytoskeleton. These results
      suggest a model in which transient activation of protein kinase A results in
      increased local concentration of LFA-1 at the cell surface and in augmented long
      term adhesion mediated by this integrin.

PMID- 1352528
TI  - Lymphocyte adhesion mediated by lymphocyte function-associated antigen-1. II.
      Interaction between phorbol ester- and cAMP-sensitive pathways.
AB  - Ag independent adhesion between lymphocytes and target cells is mediated in part
      by the interaction between lymphocyte function associated Ag-1 (LFA-1) and its
      coreceptor intercellular adhesion molecule-1 (ICAM-1). Within minutes, PMA
      treatment of JY cells, which express both LFA-1 and ICAM-1, induced capping of
      LFA-1 and augmentation of intercellular adhesion lasting for several hours.
      However, over the course of 15 to 30 min, both of these events were blocked by
      elevation of intracellular cAMP concentration ([cAMP]i) presumably via activation
      of protein kinase A. This short term inhibition of protein kinase C-induced
      adhesion was in contrast to the long term augmentation of adhesion caused by
      increased [cAMP]i as demonstrated in the companion article. Intercellular
      adhesion, due to LFA-1/ICAM-1 interactions, could also be induced by LPS
      treatment of JY cells. At submaximal concentrations, the extent of aggregation
      induced by LPS had two maxima, one at 30 to 60 min and the other with a plateau
      at 5 to 8 h. LPS is known to activate protein kinase C and we show that LPS
      treatment induced increased [cAMP]i. Using inhibitors of protein kinases C and A,
      possible mediators of the two components of adhesion induced by LPS could be
      identified. The early component was abrogated by inhibition of protein kinase C
      although the later component was unaffected. In contrast, an inhibitor of protein
      kinase A had no affect on the early component and attenuated, but did not
      entirely eliminate, the late component. These results suggest a model of
      sequential induction, inhibition, and reinduction of LFA-1/ICAM-1-mediated
      lymphocyte adhesion that is regulated by temporally ordered actions and
      interactions of protein kinases C and A.

PMID- 1352529
TI  - Demonstration of a CD3+ lymphocyte subset in the epidermis of athymic nude mice.
      Evidence for T cell receptor diversity.
AB  - The existence of CD3/TCR-bearing lymphocytes in athymic and thymectomized
      chimeric mice implies that T cell maturation can occur in the absence of a
      thymus. Considering the possibility that the epidermis may be one of the organs
      providing T cell educating stimuli, we attempted to characterize the Thy-1+
      epidermal lymphocyte population of athymic mice. Immunohistologic studies of
      epidermal sheets revealed (1) that Thy-1+ epidermal cells of C57BL/6 nu/nu mice
      are CD5-, CD4-, and predominantly CD8-, and (2) that a minor subset of these
      cells displays anti-CD3 epsilon reactivity. Although these CD3+ epidermal cells
      could hardly be detected at 6 wk of age, they comprised approximately 2% of all
      Thy-1+ epidermal cells in 12-mo-old athymic mice. Most of these CD3+ cells
      expressed TCR-gamma/delta, but TCR-alpha/beta+ cells were also present. TCR
      gamma/delta+ epidermal T cells of athymic mice preferentially expressed TCR V
      gamma 2, V gamma 4, and V gamma 5 specificities rather than TCR V gamma 3 as
      found on DETC of euthymic mice. Using mitogenic stimuli, we have succeeded in
      establishing cell lines and clones from BALB/c nu/nu and C57BL/6 nu/nu epidermis.
      Their marker profile corresponds to that seen on resident CD3+ epidermal cells,
      as well as on a very small subset of CD3+ splenic and lymph node lymphocytes of
      athymic mice. The ontogenetic relationship, if any, between the epidermal and
      lymphoid CD3+, CD5-, CD4-, CD8- cells, has yet to be clarified. Cell lines/clones
      representative of resident CD3+ epidermal cells of nu/nu mice should provide a
      useful tool in the elucidation of homing patterns and functional properties of
      extrathymically matured T cells.

PMID- 1352530
TI  - Cloning and functional expression of the T cell activation antigen CD26.
AB  - A cDNA encoding the T cell activation Ag CD26 was isolated from human PHA
      activated T cells by using an expression cloning method. The nucleotide sequence
      obtained predicts a protein of 766 amino acids of type II membrane topology, with
      six amino acids in the cytoplasmic region. The predicted amino acid sequence of
      the Ag was 85% homologous to that of the dipeptidyl peptidase IV enzyme isolated
      from rat liver. Derivatives of the human leukemic T cell line Jurkat transfected
      with a CD26 expression plasmid were established. Characterization of the CD26 Ag
      expressed by the transfected Jurkat cells revealed that the Ag could be
      immunoprecipitated as a 110-kDa molecule similar to that found on peripheral
      blood T cells and that the Ag had dipeptidyl peptidase IV activity. Functional
      analysis of these Jurkat transfectants showed that cross-linking of the CD26 and
      CD3 Ag with their respective antibodies resulted in enhanced intracellular
      calcium mobilization and IL-2 production. These results provide direct evidence
      that the CD26 Ag plays a role in T cell activation.

PMID- 1352531
TI  - Sequential analysis of T cells in the liver during murine listerial infection.
AB  - Phenotypes and functions of T cells in the liver were studied after an i.p.
      inoculation with viable Listeria monocytogenes in mice. T cells in the liver of
      untreated C3H/HeN mice (C3H; H-2k, Mls-2a) contain Thy-1.2+TCR-alpha beta + cells
      as a majority and Thy-1.2+TCR-gamma delta + cells and Thy-1.2-TCR-gamma delta +
      cells as minorities. The liver of untreated C3H mice did not contain T cells
      expressing V beta 3 and V beta 11, which are potentially autoreactive against
      self-superantigens of Mls-2a and Dvbl, respectively. On days 3 to 6 after
      infection, Thy-1.2-CD4lowTCR-alpha beta + T cells or Thy-1.2-TCR-gamma delta + T
      cells increased significantly in number and proportion in the liver whereas T
      cells with these phenotypes were hardly detected in the spleen, lymph nodes,
      peripheral blood, and peritoneal cavity during the course of the infection. The
      Thy-1.2-CD4lowTCR-alpha beta T cells contained V beta 3 or V beta 11-bearing
      cells in high frequencies. The potentially autoreactive V beta 3- or V beta 11
      bearing T cells disappeared from the liver on day 7 after infection. Furthermore,
      the V beta 3+ and V beta 11+ cells but not V beta 8+ cells disappeared after
      culture for 24 h at 37 degrees C. In vitro stimulation of liver T cells using
      anti-V beta 11 mAb showed no proliferative response. These results suggest that
      the potentially autoreactive clones with Thy-1.2-CD4low phenotypes, which
      increased in number after listerial infection, may be anergized after interaction
      with self-Ag and may be programmed to die. These potentially autoreactive clones
      induced in the liver of Listeria-infected mice may not be functionally relevant
      to the host defense against Listeria.

PMID- 1352533
TI  - The 1st International Conference on the Varicella-Zoster Virus. Harriman, New
      York, 29-31 October 1991.

PMID- 1352532
TI  - Human myoblasts as antigen-presenting cells.
AB  - Human myoblasts, cultured from muscle and purified to greater than 95%, were
      investigated for their capacity to act as facultative APC. The myoblasts reacted
      with antidesmin mAb and had the capacity to fuse into multinucleated myotubes in
      appropriate medium. The expression of HLA class I, HLA-DR, HLA-DP, HLA-DQ,
      intercellular adhesion molecule-1 (ICAM-1/CD54), lymphocyte function-associated
      (LFA) molecules LFA-1 (CD11a/CD18), LFA-2 (CD2), and LFA-3 (CD58) was
      investigated by FACS analysis before and after induction for various times with
      human rIFN-gamma, TNF-alpha, or both. Without cytokine induction, myoblasts
      expressed only HLA-class I and LFA-3. IFN-gamma alone or in combination with TNF
      alpha induced the expression of HLA-DR and ICAM-1 reaching a plateau after 48 h,
      followed by HLA-DP and even later HLA-DQ. TNF-alpha alone induced only ICAM-1.
      The functional capacity of myoblasts to present Ag to CD4+ T cells was
      investigated using autologous T cell lines specific for tuberculin, tetanus
      toxoid, and human myelin basic protein. Noninduced myoblasts or myoblasts treated
      with TNF-alpha alone could not present any of these Ag to the T cells. However,
      myoblasts treated with IFN-gamma induced Ag-specific proliferation. In the
      presence of relevant Ag, myoblasts were killed by the T cells as observed by
      microscopy and measured by 51Cr release. Ag-specific T cell proliferation and
      myoblast killing was inhibited in the presence of anti-DR mAb. These results
      suggest that human myoblasts may act as facultative APC during local immune
      reactions in muscle.

PMID- 1352534
TI  - Do drug regulations affect medical practice?

PMID- 1352535
TI  - Sufentanil: clinical use as postoperative analgesic--epidural/intrathecal route.
AB  - Although morphine and fentanyl remain the predominant epidural opioids,
      sufentanil offers some unique advantages. Because of its greater lipophilicity
      and mu-receptor binding capacity, sufentanil has a faster onset of action and
      longer duration than epidural fentanyl. Compared with morphine, sufentanil has
      been associated with a lower incidence of side effects, particularly delayed
      respiratory depression. The effective doses and adverse effects profile of
      epidural sufentanil are relatively well understood. Ventilatory depression is
      minimal with both bolus and continuous administration. Rapid vascular uptake
      after large epidural bolus, however, has been associated with acute-onset
      respiratory depression and even respiratory arrest. Sufentanil is more ideally
      suited than morphine to continuous epidural administration. The faster onset in
      comparison with fentanyl may make sufentanil the ideal agent for patient
      controlled epidural analgesia. The synergistic effect of combined sufentanil and
      low-concentration bupivacaine offers advantages over sufentanil alone. High doses
      of epidural sufentanil have been uniquely associated with cessation of shivering
      and hypothermia. As with fentanyl, the intrathecal administration of sufentanil
      for postoperative analgesia is limited by its short duration of action.

PMID- 1352536
TI  - Modified taxols, 7. A method for the separation of taxol and cephalomannine.

PMID- 1352537
TI  - Molecular genetics of Leber's hereditary optic neuropathy: study of a six
      generation family from Western Australia.
AB  - Molecular genetic studies were carried out on a 6-generation family from Western
      Australia with Leber's hereditary optic neuropathy. Pedigree analysis confirms
      the maternal inheritance of the genetic lesion underlying the disorder in this
      family. The presence of a recently reported disease-associated mutation at
      nucleotide 11778 of the mtDNA was established in one clinically affected family
      member by the sequencing of an appropriate 1.6 kb PCR-amplified fragment of the
      mtDNA; this mutation leads to an Arg340----His amino acid replacement in the ND4
      subunit of respiratory complex I. The 11778 G to A base substitution is
      associated with the loss of an SfaNI restriction site. Examination of the
      representative members for this site revealed that while only mtDNA carrying this
      substitution could be detected in the leukocytes of 4 family members of the sixth
      generation, the mutated mtDNA was found to co-exist with the normal mtDNA
      population (heteroplasmy) in a clinically unaffected member from the fifth
      generation. This observation suggests that the nt 11778 mutation observed in this
      LHON family is relatively new; the observation of both heteroplasmy and apparent
      homoplasmy of the mtDNA in different family members might reflect the normal
      progression in the establishment of a mitochondrially inherited mutation.

PMID- 1352538
TI  - T-cell phenotypic profiles in the cerebrospinal fluid and peripheral blood of
      multiple sclerosis patients.
AB  - Thirty-nine patients with clinically definite multiple sclerosis (MS) entered the
      study. Of 28 subjects with a relapsing-remitting course, 19 were classified in
      acute relapse, 9 in remission; 11 patients had a progressive course without
      remissions. Furthermore, 6 subjects with inflammatory neurological disease (IND),
      and 10 with non-inflammatory and non-neoplastic neurological disease (NIND) were
      investigated. We simultaneously studied cerebrospinal fluid (CSF) and peripheral
      blood (PB) T-, B- and NK-cell subsets, as defined by following monoclonal
      antibodies: anti-CD3, -CD4, -CD8, -CD19, -CD16, -HLA-DR and -IL-2-R. We found a
      significant increase of CD4+ T-cells compared with controls in CSF, with respect
      to PB, of MS patients, particularly in acute relapse. An increase of HLA-DR+ cell
      percentages in the CSF than in the PB in all MS groups, especially in attacks of
      MS but also in remission, was also observed, with a positive correlation between
      CD4+ T-cell and DR+ cell percentages both in the CSF as well as in the PB of
      relapsing MS patients. These findings, together with the increase of IL-2-R+
      cells in the PB, particularly in relapsing MS, give further support for the
      presence of a systemic T-cell activation in MS.

PMID- 1352539
TI  - The probable conformation of substrates recognized by dipeptidyl-peptidase IV and
      some aspects of the catalytic mechanism derived from theoretical investigations.
AB  - By theoretical conformational investigations of substrates and nonsubstrates of
      the enzyme dipeptidyl-peptidase IV (DP IV) as well as dipeptide-esters using the
      ECEPP83 method we determined the structure of peptides recognized and cleaved by
      the enzyme. From a comparison of all possible structures for the substrates with
      conformations not possible in nonsubstrates we concluded that a single
      conformation explains substrate specificities of DP IV. This conformation is
      characterized by the following dihedral angles: psi 1 = 85 degrees, omega 1 = 180
      degrees, phi 2 = -75 degrees, psi 2 = 80 degrees, and omega 2 = 180 degrees. The
      conclusions were supported by comparisons of molecular electrostatic potentials
      calculated with the molecular graphics program HAMOG.

PMID- 1352540
TI  - Changes in gamma-aminobutyric acid and somatostatin in epileptic cortex
      associated with low-grade gliomas.
AB  - The role of specific neuronal populations in epileptic foci was studied by
      comparing epileptic and non-epileptic cortex removed from patients with low-grade
      gliomas. Epileptic and nearby (within 1 to 2 cm) non-epileptic temporal lobe
      neocortex was identified using electrocorticography. Cortical specimens taken
      from four patients identified as epileptic and nonepileptic were all void of
      tumor infiltration. Somatostatin- and gamma-aminobutyric acid (GABAergic)
      immunoreactive neurons were identified and counted. Although there was no
      significant difference in the overall cell count, the authors found a significant
      decrease in both somatostatin- and GABAergic-immunoreactive neurons (74% and 51%,
      respectively) in the epileptic cortex compared to that in nonepileptic cortex
      from the same patient. It is suggested that these findings demonstrate changes in
      neuronal subpopulations that may account for the onset and propagation of
      epileptiform activity in patients with low-grade gliomas.

PMID- 1352542
TI  - Immunoreactivity for P-170 glycoprotein in malignant mesothelioma and in non
      neoplastic mesothelium of the pleura using the murine monoclonal antibody JSB-1.
AB  - The results of an immunohistochemical study of P-170 glycoprotein
      immunoreactivity in human non-neoplastic mesothelium (35 cases) and in malignant
      mesothelioma (33 cases) using the murine monoclonal antibody JSB-1 are reported.
      The majority of malignant mesothelioma cases exhibited cytoplasmic and membrane
      immunoreactivity in neoplastic cells. These findings are highly significant when
      compared with the absence of immunoreactivity in normal mesothelium.

PMID- 1352541
TI  - Potential for hepatic and renal dysfunction during influenza B infection,
      convalescence, and after induction of secondary viremia.
AB  - Whether infection with influenza B virus alters hepatic function was examined in
      the ferret. Also, the possibility that viral-specific antibodies (Ab) could be
      produced well before their detection in serum was explored. During the febrile
      period of influenza, reductions in the serum potassium, anion gap, ammonia,
      albumin and CPK and elevations of the BUN, creatinine and the GGTP levels
      occurred. With convalescence, the electrolytes, BUN and creatinine normalized,
      FFA, SGPT and CPK levels rose and the serum GGTP rose even further. Hepatic fatty
      acid (FA) oxidation, ornithine transcarbamylase (OTC) and carnitine
      palmitoyltransferase (CPT) activities were minimally altered and liver ATP and
      total lipid content remained normal. Following experimental secondary viremia,
      serum FFA continued to rise, TG decreased and CPK remained elevated while SGPT
      and GGTP levels normalized. In the liver, FA oxidation and OTC rates remained
      unchanged but CPT activity was inhibited and the liver content of ATP was
      significantly reduced. Immune complex (IC) protein recovered from postmicrosomal
      supernatant fractions by polyethylene glycol precipitation was progressively
      increased in livers from convalescent and viremic animals. While the amount of IC
      protein recovered in the spleen also increases during convalescence, this is not
      the case after viremia when the IC formed seem to be processed largely by the
      liver. By SDS/PAGE, the major proteins identified in the IC were IgM and other
      viral proteins. However, the viral proteins could not be validated by immunoblot
      with Ab produced against purified influenza B hemagglutinin (HA) and
      neuraminidase (NA) most probably due to phagocytic alterations of glycoprotein
      immunodeterminants. These findings indicate that during influenza, convalescence
      and post viremia changes in the concentrations of several serum and liver
      components occur that reflect hepatic involvement. Also, antiviral Ab, largely
      IgM, appears to be produced early, complexes with Ag and can be found sequestered
      in both the liver and spleen at a time when Ab is not detectable in the serum.

PMID- 1352543
TI  - Effects of ursodeoxycholic acid on liver function in patients with cystic
      fibrosis and chronic cholestasis.
AB  - Ursodeoxycholic acid, 10 to 20 mg/kg per day, was administered for 1 year to 22
      patients with cystic fibrosis and chronic cholestasis, resulting in significantly
      improved liver enzyme values. However, evidence of cholestasis continued, as
      shown by the pattern of alkaline phosphatase isoenzymes.

PMID- 1352544
TI  - Benign recurrent cholestasis with normal gamma-glutamyl-transpeptidase activity.
AB  - We report two observations of intrahepatic cholestasis with normal serum levels
      of gamma-glutamyl-transpeptidase. These cases fit the diagnostic criteria of
      benign recurrent cholestasis and show that it, like Byler disease, is another
      form of pediatric intrahepatic cholestasis with a normal gamma-glutamyl
      transpeptidase level in the infant.

PMID- 1352545
TI  - Proceedings of the 17th Symposium on Progress in Organic Reactions and Syntheses.
      Fukuoka, November 7-8, 1991. Abstracts.

PMID- 1352546
TI  - Expression of the multidrug-resistant gene in human musculoskeletal tumors.
AB  - We measured the levels of messenger RNA of the human multidrug-resistant (MDR)
      gene in 15 human musculoskeletal tumors. In metastatic tumors and those which did
      not respond to combination chemotherapy, there was an increased expression of
      this gene. No evidence of expressions of the MDR gene was found in the benign
      tumors. The high expression of the MDR gene from musculoskeletal tumors
      apparently induced a multidrug resistance, and this acquired resistance may be
      due to outgrowth of the P-glycoprotein-expressing MDR tumor. Elucidation of
      expression of the MDR gene is an important step in malignant musculoskeletal
      tumors research.

PMID- 1352547
TI  - Functional evidence for multiple gamma-aminobutyric acidB receptor subtypes in
      the rat cerebral cortex.
AB  - The aim of this work was the identification of pharmacologically distinct
      subtypes of gamma-aminobutyric acidB (GABAB) receptors in the central nervous
      system. Inasmuch as GABAB receptors are often sited on axon terminals where they
      mediate inhibition of transmitter release, we chose as models the GABAB receptors
      mediating inhibition of release of 1) endogenous GABA; 2) endogenous glutamate;
      and 3) somatostatin-like immunoreactivity (SRIF-LI). The experimental set up
      consisted of rat cerebrocortical synaptosomes depolarized in superfusion with 12
      or 15 mM KCl. Endogenous GABA and glutamate were measured by high-performance
      liquid chromatography and SRIF-LI by radioimmunoassay. The selective GABAB
      receptor agonist (-)-baclofen inhibited in a concentration-dependent manner the
      K(+)-evoked release of GABA, glutamate and SRIF-Ll with similar potencies and
      efficacies [EC50 values, 1.1-1.5 microM; maximal inhibition, 45-50% at about 10
      microM (-)-baclofen]. The GABAB receptor antagonist phaclofen concentration
      dependently reduced the effects of (-)-baclofen on the release of GABA and SRIF
      Ll but not on the release of glutamate, where it was ineffective up to 1000
      microM. The rank order of potency (Ki values are shown in parentheses) are: SRIF
      Ll (7.8 microM); GABA (10.4 microM); and glutamate (greater than 115 microM). The
      novel GABAB receptor antagonist 3-aminopropyl(diethoxymethyl) phosphinic acid
      (CGP 35348) displayed a different pattern on the three release systems examined
      (Ki values are shown in parentheses): SRIF-Ll (0.38 microM); glutamate (0.48
      microM); and endogenous GABA (greater than 115 microM).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1352548
TI  - Involvement of 5-hydroxytryptamine1A receptors in the modulation of micturition
      reflexes in the anesthetized rat.
AB  - Intravenous administration of the selective 5-hydroxytryptamine (5-HT)1A receptor
      agonist 8-hydroxy-2-(di-N-propylaminotetralin (8-OH-DPAT) and of a low doses of
      buspirone elicited the supraspinal micturition reflex (SMR) in urethane
      anesthetized rats when the urinary bladder was filled with just a subthreshold
      volume of saline (threshold conditions). The effect of i.v. 8-OH-DPAT was
      abolished by hexamethonium or spiroxatrine. When SMR was elicited by bladder
      distension (suprathreshold conditions), i.v. 8-OH-DPAT increased the frequency of
      bladder contractions. In threshold conditions, stimulation of SMR was also
      induced by i.c.v. or by i.t. administration of 8-OH-DPAT and 5-HT but not by
      topical application of 8-OH-DPAT onto the bladder. Guanethidine pretreatment,
      which produced detrusor hyperreflexia, antagonized the effect of both i.c.v. and
      i.t. 8-OH-DPAT. In rats treated with capsaicin as adults, the response to 8-OH
      DPAT was unchanged. In rats treated with capsaicin as newborns, instead, the
      response to i.t. 8-OH-DPAT was abolished and that to i.c.v. 8-OH-DPAT was shifted
      to higher doses. Pretreatment with 5,7-dihyroxytryptamine did not affect the
      response to i.t. 8-OH-DPAT but shifted to higher doses the response to i.c.v. 8
      OH-DPAT. Intravenous administration of spiroxatrine, methysergide, NAN-190 [1-(2
      methoxyphenyl)-4-[4-(2-phtalimido)butyl] piperazine] or high doses of buspirone
      but not of 1-sulpiride inhibited SMR in suprathreshold conditions. The inhibitory
      effect of spiroxatrine, NAN-190 and buspirone was not reduced by guanethidine
      pretreatment. In chronically spinalized animals, i.v. 8-OH-DPAT increased the
      amplitude of the reflex bladder contractions induced by bladder
      distension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352549
TI  - Pharmacological characterization of chick and frog beta adrenergic receptors in
      primary cultures of myocardial cells.
AB  - In membrane preparations derived from primary cultures of chick myocardial cells,
      beta adrenergic receptors modeled for a single low-affinity site for both
      betaxolol (beta-1-selective) and ICI 118551 (beta-2-selective) displacement of
      [125I]iodocyanopindolol (ICYP), indicating that the chick beta receptor is
      pharmacologically distinct from both mammalian beta-1 and beta-2 adrenergic
      receptors with respect to these antagonists. However, the highly beta-1-selective
      compound CGP 20712A was able to distinguish two binding sites on ICYP competition
      curves, a high-affinity "beta-1 site" (75%) and a low-affinity "beta-2 site"
      (25%). Also, in chick heart cell membranes the relative ability of agonists to
      displace ICYP produced a profile typical of beta-1 adrenergic receptors with a
      rank order of potency or efficacy of: isoproterenol greater than epinephrine =
      norephinephrine. When agonist-mediated adenylyl cyclase stimulation was assessed
      the order of potency was slightly different, isoproterenol greater than
      epinephrine greater than or equal to norepinephrine. Additionally, antagonism of
      isoproterenol stimulation of adenylyl cyclase by CGP 20712A yielded a Kb value
      (1.16 +/- 0.35 x 10(-7) M) intermediate between the high and low-affinity binding
      sites of CGP 20712A, suggesting that the low-affinity site is coupled to adenylyl
      cyclase. In membrane preparations of frog myocardial cells, ICYP/antagonist
      competition curves modeled for a mixed population of receptors, with subtype
      percentages varying from 50:50 beta-1:beta-2 to 100% beta-2 depending on the
      specific antagonist used and the individual cell preparation. For ICYP/agonist
      competition binding experiments the relative ability to displace ICYP was
      isoproterenol greater than epinephrine = norepinephrine, a profile typical of
      beta-1 adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352550
TI  - Cytochrome P-450 mediates bioactivation of organic nitrates.
AB  - The cellular mechanism of bioactivation underlying guanylate cyclase activation
      by organic nitrates was investigated. In cultured rat lung fibroblasts (RFL-6
      cells), the inhibitor of cytochrome P-450 proadifen (0.1 mM) decreased cyclic GMP
      stimulation by glyceryl trinitrate (GTN, 1-100 microM) by up to 81%. Cyclic GMP
      stimulation by isoidide dinitrate was inhibited to a similar degree under these
      conditions. However, proadifen did not affect cyclic GMP stimulation by sodium
      nitroprusside that spontaneously releases nitric oxide. Cyclic GMP stimulation in
      RFL-6 cells by GTN remained unaltered in the presence of the inhibitor of
      glutathione S-transferase sulfobromophthalein. In the same cell type, a 24-hr
      pretreatment with the inducer of cytochrome P-450 3-methylcholanthrene (10
      microM) augmented cyclic GMP stimulation by GTN or isoidide dinitrate by up to
      102%. Cultured porcine aortic endothelial cells were found to be without a cyclic
      GMP response to GTN, although sodium nitroprusside produced a marked cyclic GMP
      elevation in these cells. The endothelial cells remained unresponsive to GTN even
      in the presence of N-acetylcysteine (5 mM). Moreover, in a cell-free preparation
      from rat liver, glutathione-dependent biotransformation of GTN was not
      accompanied by activation of soluble guanylate cyclase. These findings suggest
      that in intact cells bioactivation of, i.e., nitric oxide formation from organic
      nitrates is mediated by a cytochrome P-450 enzyme system rather than by
      glutathione S-transferase or free thiols.

PMID- 1352551
TI  - Central effects of quinpirole on blood pressure of spontaneously hypertensive
      rats.
AB  - The i.v. administration of the dopamine D-2 receptor agonist quinpirole induced a
      rapid increase in blood pressure in spontaneously hypertensive rats (SHR). Heart
      rate showed little change. The pressor response to quinpirole was similar in SHR
      and normotensive Wistar-Kyoto rats (WKY) at doses of 0.03 to 0.3 mg/kg but, at 1
      mg/kg, quinpirole induced a greater increase in blood pressure in SHR than in
      WKY. In contrast, although both strains showed a decreased locomotor activity
      after administration of 0.01 to 0.05 mg/kg of quinpirole, only in WKY was
      activity enhanced by 0.25 to 1.25 mg/kg of quinpirole. The i.v. administration of
      the dopamine agonists apomorphine, N-propylnorapomorphine and (R)-(+)-3-(3
      hydroxyphenyl)-N-propylpiperidine, but not the putative presynaptic D-2 agonist
      (S)-(-)-3-(3-hydroxyphenyl)-N- propylpiperidine, induced pressor responses in SHR
      comparable to those after quinpirole administration. The pressor effect of
      quinpirole was enhanced by pretreatment with the peripheral D-2 antagonist
      domperidone, but blocked by the centrally acting dopamine antagonists haloperidol
      or sulpiride. In SHR, which were pretreated centrally with pertussis toxin,
      quinpirole induced a significantly smaller increase in blood pressure than in
      control SHR. Pretreatment centrally with 6-hydroxydopamine had no effect on the
      pressor action of quinpirole in SHR. Thirty minutes after i.v. administration of
      quinpirole, an additional injection of quinpirole did not significantly change
      blood pressure. Increasing the interval between two subsequent injections of
      quinpirole showed that this desensitization slowly reversed, but only after 24 hr
      had the pressor response to quinpirole fully recovered.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1352552
TI  - Serotonin-stimulated release of [3H]dopamine via reversal of the dopamine
      transporter in rat striatum and nucleus accumbens: a comparison with release
      elicited by potassium, N-methyl-D-aspartic acid, glutamic acid and D-amphetamine.
AB  - Release of preloaded radiolabeled dopamine ([3H]DA) elicited by several agents
      from terminal fields of mesolimbic and nigrostriatal projections in rats was
      compared. Several similarities between the two areas were observed. For example,
      potassium, which stimulates release both directly, through altering the potential
      across the membrane of the dopaminergic neuron, as well as indirectly, presumably
      by releasing endogenous excitatory neurotransmitters, exhibited some similarities
      to release stimulated by L-glutamate and N-methyl-D-aspartic acid. These included
      sensitivity to tetrodotoxin (TTX), Mg++ and Ca++. In contrast, release of [3H]DA
      stimulated by serotonin (5-HT), like that stimulated by D-amphetamine, depended
      upon a functional dopamine transport system and was less sensitive to TTX, Mg++
      and Ca++. 5-HT-stimulated [3H]DA release in striatum (STR) and nucleus accumbens
      (NACC) was not modified by antagonists at 5-HT2 or 5-HT3 receptors. Differences
      were observed in release of [3H]DA from STR and NACC. Elevated potassium (20 mM)
      released about twice as much [3H]DA from NACC as it did from STR. 5-HT was also
      able to release more [3H]DA from NACC than from STR. Conversely, D-amphetamine
      released more [3H]DA from STR than from NACC. TTX increased release stimulated by
      potassium in STR, but decreased release stimulated by potassium in NACC. These
      observations suggest that receptor- and non-receptor-mediated mechanisms may
      contribute to regulation of [3H]DA release in mesolimbic and nigrostriatal areas
      of the brain. It is possible that endogenous 5-HT in STR or NACC acts as a local
      regulator of DA release acting via a transport-dependent mechanism.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1352553
TI  - Dihydrexidine, a novel full efficacy D1 dopamine receptor agonist.
AB  - The present work provides a detailed pharmacological characterization of
      dihydrexidine (DHX) (trans-10,11-dihydroxy- 5,6,6a,7,8,12b
      hexahydrobenzo[a]phenanthridine), the first high-potency, full efficacy,
      bioavailable D1 dopamine receptor agonist. DHX represents a new conformationally
      rigid structural class of dopamine receptor ligands. It competes
      stereoselectively and potently for D1 binding sites in rat striatal membranes
      labeled with [3H]SCH23390 with an IC50 of about 10 nM compared to about 30 nM for
      the prototypical D1 agonist SKF38393. Like other dopamine agonists, DHX has a
      shallow competition curve (nH = ca. 0.7) that can be fitted by a two-site model
      consisting of high-affinity (63%; KD = 3 nM) and low-affinity (37%; KD = 75 nM)
      sites. DHX was screened for activity against 40 other binding sites, and was
      inactive (IC50 greater than 10 microM) against all except D2 dopamine receptors
      (IC50 = 130 nM) and alpha 2 adrenoreceptors (IC50 = ca. 230 nM). Functionally,
      DHX is a full efficacy dopamine D1 agonist. In homogenates of rat striatum, DHX
      or dopamine doubles the rate of cyclic AMP synthesis, whereas SKF38393 only
      causes a maximal increase of about 50%. These effects of DHX are blocked by the
      selective D1 antagonist SCH23390, but are not affected by D2, 5
      hydroxytryptamine2, muscarinic, or alpha or beta adrenergic antagonists. Because
      DHX is known to cause D2-like behavioral effects at high doses, the nature of its
      D2 activity was characterized using prolactin release as an end-point. DHX and
      the prototypical D2 agonist quinpirole both caused a significant inhibition of
      the prolactin release induced by 5-hydroxytryptophan. These effects of DHX are
      not due to "indirect" alterations at the presynaptic terminal, because DHX is
      essentially inactive at inhibiting the dopamine uptake system, and does not cause
      the release of dopamine. These data demonstrate the utility of DHX for probing
      the biochemistry and function of D1 dopamine receptors.

PMID- 1352554
TI  - Relationship between brain levels of 3-(3-hydroxyphenyl)-N-n-propylpiperidine HCl
      enantiomers and effects on locomotor activity in rats.
AB  - After s.c. administration of 3-(3-hydroxyphenyl)-N-n-propylpiperidine HCl (3-PPP)
      to rats, plasma and brain levels were monitored in relation to the amount of
      spontaneous locomotor activity. Based on time-course relationships, concentration
      effect curves were elaborated after administration of (-)3-PPP and (+)3-PPP in
      the dose range of 1 to 256 mumol.kg-1. Both enantiomers were readily absorbed and
      distributed, as evidenced by a close correlation between brain and plasma levels,
      brain levels being 7 to 9 times higher than those found in plasma. Plasma half
      lives were 25 and 32 min for (-)3-PPP and (+)3-PPP, respectively. Plotting brain
      concentrations of (-)3-PPP against locomotor activity resulted in a good fit to a
      declining two-phase curve, in all probability reflecting preferential actions at
      pre- and postsynaptic dopamine receptors, respectively. These two underlying
      mechanisms could also be identified from the biphasic effects produced by (+)3
      PPP on locomotor activity: suppression followed by stimulation, respectively.
      Together, these observations provide further support for the contention that at
      low doses, both enantiomers have sedative actions due to stimulation of
      inhibitory autoreceptors. With increasing doses, however, a postsynaptic receptor
      blockade will predominate for a partial agonist like (-)3-PPP, producing
      suppression of locomotion, whereas the full agonist, (+)3-PPP, will produce
      behavioral activation due to stimulation of postsynaptic receptors.

PMID- 1352555
TI  - Neuroanatomical sites mediating the central actions of beta-endorphin as mapped
      by changes in glucose utilization: involvement of mu opioid receptors.
AB  - Local cerebral glucose utilization, which is a correlate of neuronal activity,
      was measured to obtain information on the neuroanatomical sites mediating the
      different behaviors elicited by i.c.v. administration of the opioid peptide beta
      endorphin (beta-END). The selective mu and delta opioid receptor antagonists d
      Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) and ICI 174,864 (N,N-diallyl-Tyr-Aib
      Aib-Phe-Leu-OH), respectively, were used to characterize the opioid receptor type
      involved in the actions of beta-END. beta-END was found to produce profound
      increases in glucose utilization in limbic regions such as the lateral septal
      nucleus, the amygdalo-hippocampal transition area, the nucleus accumbens and the
      hippocampal formation. The ventral hippocampus proved the most sensitive
      structure, displaying increases in glucose utilization of up to 200%; changes in
      the dorsal part amounted up to 100%. Only moderate effects were induced by beta
      END in motor areas, such as the substantia nigra, pars reticulata and the nucleus
      ruber. This regional pattern of changes is assumed to underlie the epileptogenic
      , motivational-, mood- and possibly memory-modulating actions of beta-END. The
      effects of beta-END on local cerebral glucose utilization were blocked by
      pretreatment with the mu antagonist, CTOP, whereas the selective delta opioid
      antagonist ICI 174,864 was less effective. An involvement of predominantly mu
      opioid receptors in the central actions of beta-END is, therefore, suggested.

PMID- 1352556
TI  - Profile of action of a novel 5-hydroxytryptamine1A receptor ligand E-4424 to
      inhibit aversive behavior in the mouse, rat and marmoset.
AB  - E-4424 (2-(4-[4-(4-chloro-1-pyrazolyl)butyl]-1-piperazinyl)pyrimidine) was shown
      to be a 5-hydroxytryptamine1A receptor ligand in radioligand binding assays and
      in an in vitro guinea pig ileum preparation had both 5-hydroxytryptamine1A
      antagonist and agonist effects. The antagonist/agonist ratio of E-4424 was
      greater than in the case of buspirone and ipsapirone. E-4424 was compared to
      diazepam, buspirone and ipsapirone to inhibit the behavioral response to an
      aversive situation in the mouse black and white test box, the rat social
      interaction test and a marmoset human threat test. The acute administration of E
      4424 (0.0001-0.5 mg/kg, i.p.) to the mouse decreased aversion to the white area
      of the test box and was as effective as diazepam (0.125-1.0 mg/kg, i.p.) and much
      more potent than buspirone (0.25-1.0 mg/kg, i.p.) or ipsapirone (0.5-5.0 mg/kg,
      i.p.). E-4424 was also effective in enhancing rat social interaction and reducing
      anxiety-related behaviors in the marmoset and was again more potent than
      diazepam, buspirone or ipsapirone. Withdrawal from a 14-day administration of
      diazepam, cocaine, nicotine or alcohol exacerbated the response to the aversive
      situation in the mouse test. This was not observed after withdrawal from a
      chronic treatment with E-4424, buspirone or ipsapirone. However, E-4424
      administered during drug withdrawal prevented the response caused by withdrawal
      from cocaine, alcohol, nicotine and diazepam: buspirone was ineffective and
      ipsapirone only attenuated that syndrome after alcohol withdrawal.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1352557
TI  - Mosquito and arbovirus ecology in southeastern California, 1986-1990.
AB  - Mosquito abundance and western equine encephalomyelitis (WEE) and St. Louis
      encephalitis (SLE) virus activity were monitored in five valleys in southeastern
      California from June 1986 through April 1990 to study virus overwintering and
      possible dissemination from south to north along geographically defined
      corridors. Culex tarsalis Coquillett predominated in CO2 trap collections and was
      the only species repeatedly infected with WEE and SLE viruses. Abundance peaked
      during April-May and August-October. WEE virus infections in Cx. tarsalis
      generally were detected after the spring peak and were followed approximately 1
      mo later by seroconversions in sentinel chickens. SLE virus infections occurred
      later in the summer but before the fall peak in Cx. tarsalis abundance. Peak Cx.
      tarsalis abundance occurred when monthly temperatures averaged 25 degrees C,
      whereas virus infections generally were detected most frequently when
      temperatures exceeded 29 degrees C. Although the spring increase in Cx. tarsalis
      abundance occurred earlier in southern valleys, the onset of virus activity was
      variable among valleys and did not follow a south to north progression.

PMID- 1352558
TI  - Coronary ostial endarterectomy in Takayasu's aortitis--confirmation of patency
      nine years postsurgically.
AB  - A case of Takayasu's aortitis with severe bilateral coronary ostial stenosis is
      reported. A transaortic coronary endarterectomy was performed and sufficient
      patency was confirmed angiographically 9 years after the operation. This is the
      first report of late coronary angiography after a transaortic coronary ostial
      endarterectomy in Takayasu's aortitis. The efficacy of this procedure for
      coronary ostial stenosis in Takayasu's aortitis is emphasized.

PMID- 1352559
TI  - Neuroleptic malignant syndrome.
AB  - NMS is a life-threatening, hyperpyrexic syndrome that follows the blockage of
      certain central dopaminergic receptor sites; it is commonly associated with the
      use of neuroleptic medications. Clinical signs usually include hyperthermia,
      altered mental status, muscle rigidity, and autonomic instability. Treatment is
      mainly supportive. Dopamine agonists and muscle relaxants are often used in
      therapy; however, their effectiveness has never been adequately determined in
      controlled studies.

PMID- 1352560
TI  - Assessment of X-chromosome inactivation patterns using the hypervariable probe
      M27 beta in normal hemopoietic cells and acute myeloid leukemic blasts.
AB  - The value of the hypervariable X-linked probe M27 beta for use in the analysis of
      X-chromosome inactivation patterns in normal blood and bone marrow cells and in
      the assessment of clonality in acute myeloid leukemia (AML) blast cells has been
      determined. By electrophoresing samples for 30 h, heterozygosity of the M27 beta
      locus was demonstrable in 324/415 females (78%) and this value could be increased
      to 93% by electrophoresing for 50 h. Determination of the X-chromosome
      inactivation patterns in blood and bone marrow samples from hematologically
      normal females was possible in approximately 90% of heterozygous individuals. The
      X-chromosome inactivation ratios obtained with M27 beta were comparable with
      phosphoglycerate kinase or hypoxanthine phosphoribosyl transferase in 46
      individuals heterozygous for one of these genes in addition to M27 beta. The
      results obtained were closely correlated (r = 0.89). In 21 of 35 (60%) AML
      blasts, however, there was hypermethylation of the M27 beta locus and clonal
      analysis was not possible. Hypermethylation was not related to FAB type.

PMID- 1352562
TI  - High level of HTLV-I specific protein expression in a patient with adult T-cell
      leukemia, chronic progressive myelopathy and Kaposi's sarcoma.
AB  - Analysis was made of serum anti-HTLV-I antibodies, virus-specific proteins in
      peripheral blood lymphocytes (PBL) and proviruses in lymphocyte DNA of a patient
      with adult T-cell leukemia (ATL), Kaposi's sarcoma, and chronic myelopathy. Using
      Western blot and PCR (with HIV-1 specific primers), it was shown that Kaposi's
      sarcoma was not linked to HIV infection. Western blot analysis of serum revealed
      antibodies against p19, p24 and Pr 53 of HTLV-I. Examination of proteins in fresh
      PBL by Western blot revealed a high level of HTLV-I specific protein expression.
      Southern blot analysis of the patient's DNA revealed two different sites for HTLV
      I provirus integration.

PMID- 1352561
TI  - Cell-cycle-associated expressions of proliferating cell nuclear antigen and Ki-67
      reactive antigen of bone marrow blast cells in childhood acute leukemia.
AB  - To investigate the growth characteristics of human leukemia cells, the expression
      of proliferation-associated nuclear antigens was examined in relation to cell
      cycle phases in marrow blast cells obtained from 37 untreated children with acute
      leukemia. Ki-67 monoclonal antibody reactive antigen and proliferating cell
      nuclear antigen (PCNA) were measured by the simultaneous flow cytometric analysis
      of DNA and nuclear antigens. The percentage of PCNA-positive cells was always
      higher than that of Ki-67-positive cells in individual patients. The level of
      PCNA was greatly increased in G1 or early S phase, but was generally stable in S
      and G2 phases. Accordingly, most of the cells in the proliferative compartments
      (greater than 2C DNA) showed a high expression of PCNA. In contrast, expression
      of Ki-67 antigen varied greatly from patient to patient, and differed
      significantly in different subtypes of the disease. The level of Ki-67 antigen
      increased with the cell cycle progression, showing maximum expression in late S
      and G2 phases. However, in most of the patients, a distinct population of Ki-67
      negative cells was found not only in G1 phase, but also in the proliferative
      compartments. These results appear to reflect differences in the proliferative
      activity of bone marrow blast cells in childhood acute leukemia.

PMID- 1352563
TI  - Cellular and humoral effects of naftopidil in man.
AB  - The effects of naftopidil on the intracellular concentration and transmembrane
      fluxes of Na+ and K+ in erythrocytes and on the intracellular Na+, K+ and free
      cytosolic Ca2+ concentration in platelets were studied in twenty-four normal male
      subjects, using a double-blind study design. After a run-in period on placebo for
      1 week, the subjects were treated with either placebo (n = 8) or naftopidil 25 mg
      (n = 8) or 50 mg (n = 8) once a day for 4 weeks. Intraerythrocyte Na+
      concentration and the erythrocyte anion carrier were decreased during naftopidil
      administration. No significant effect of naftopidil could be demonstrated on
      ouabain-sensitive Na+ efflux, bumetanide-sensitive Na+ efflux, ouabain,
      bumetanide-resistant Na+ and K+ efflux and Na+, Li(+)-countertransport activity
      in red blood cells or on the intraerythrocyte K+ and Mg2+ concentration. The free
      cytosolic Ca2+ and Na+ concentration in platelets was also decreased during
      naftopidil administration while no effect of naftopidil was found on the
      intracellular K+ and Mg2+ concentration in platelets.

PMID- 1352564
TI  - Effect of preservation solution on results of cadaveric kidney transplantation.
      The European Multicentre Study Group.
AB  - University of Wisconsin (UW) preservation solution has been reported to be
      beneficial for canine organ transplants and for human liver and pancreas
      transplants. To examine whether it affects renal graft survival, a randomised
      multicentre trial was conducted to compare its effect with that of EuroCollins
      solution on delayed graft function, renal function, and patient and graft
      survival in 695 recipients of cadaveric renal transplants. 352 kidneys were
      preserved with UW and 343 with EuroCollins solution. Delayed graft function
      occurred in 23% of the UW group and in 33% of the EuroCollins group (p = 0.003).
      Three factors other than type of preservation fluid were associated with a higher
      incidence of delayed graft function: older donor age, intracerebral haemorrhage
      in the donor, and oliguria in the donor. Renal function as indicated by serum
      creatinine concentration was better in the UW than in the EuroCollins group.
      Patient survival in the UW and EuroCollins groups after 1 year was 95% and 94%,
      respectively. In both groups, delayed graft function reduced 1-year graft
      survival by 15% (p = 0.0001). 1-year graft survival of UW-preserved kidneys was
      6% higher than that of controls (88.2% vs 82.5%, p = 0.04). Delayed graft
      function is significantly associated with a reduction in 1-year graft survival.
      The preservation solution is the most important factor influencing development of
      delayed graft function, and UW solution is superior to EuroCollins solution in
      reducing occurrence of delayed graft function, improving graft function,
      extending graft survival.

PMID- 1352565
TI  - Schizophrenia and city life.
AB  - Prevalence of schizophrenia and rates of first admission to hospital for this
      disorder are higher in most modern industrialised cities, and in urban compared
      with rural areas. The "geographical drift" hypothesis (ie, most schizophrenics
      tend to drift into city areas because of their illness or its prodrome) has
      remained largely unchallenged. We have investigated the association between place
      of upbringing and the incidence of schizophrenia with data from a cohort of
      49,191 male Swedish conscripts linked to the Swedish National Register of
      Psychiatric Care. The incidence of schizophrenia was 1.65 times higher (95%
      confidence interval 1.19-2.28) among men brought up in cities than in those who
      had had a rural upbringing. The association persisted despite adjustment for
      other factors associated with city life such as cannabis use, parental divorce,
      and family history of psychiatric disorder. This finding cannot be explained by
      the widely held notion that people with schizophrenia drift into cities at the
      beginning of their illness. We conclude that undetermined environmental factors
      found in cities increase the risk of schizophrenia.

PMID- 1352566
TI  - Loss of heterozygosity on chromosome 17p and mutant p53 in HPV-negative cervical
      carcinomas.
AB  - Inactivation of the protein product of the wild-type tumour suppressor gene p53
      through complexing of the protein with the E6 oncoprotein of human
      papillomaviruses (HPV) in HPV-infected cells is thought to be important in the
      aetiology of cervical carcinoma. Mutations of p53 have also been reported in HPV
      negative carcinomas, and we now demonstrate loss of heterozygosity (LOH) of
      chromosome region 17p13 (in which p53 is located) in such tumours.
      Immunocytochemical staining with monoclonal antimutant-p53 antibody revealed that
      the carcinomas with LOH on 17p and completely lacking HPV DNA sequences had
      mutant p53. Thus the LOH had apparently resulted in the loss of the wild-type
      allele. Consequently, in both HPV-positive and HPV-negative tumours there is loss
      of function of wild-type p53, in the former because the protein product of the
      p53 gene complexes with that of the viral E6 gene, in the latter because the
      protein is altered, presumably as a result of a direct alteration of the p53 gene
      but possibly because of other post-translational changes. That this mutant allele
      of the tumour suppressor gene may sometimes behave like an oncogene is suggested
      by the presence of more than the expected number of copies of the remaining
      chromosome 17 homologue in some carcinomas.

PMID- 1352568
TI  - AIDS: an opportunity not to be lost.

PMID- 1352567
TI  - Low-dose aspirin and subsequent peripheral arterial surgery in the Physicians'
      Health Study.
AB  - In the US Physicians' Health Study the early termination of the aspirin arm has
      provided the opportunity to test the hypothesis that low-dose aspirin (325 mg on
      alternate days) might affect the subsequent occurrence of peripheral arterial
      surgery. In the study, a randomised double-blind placebo-controlled trial among
      22,071 healthy US male physicians aged 40-84, there were, during an average of
      60.2 months of treatment and follow-up, 56 participants who underwent peripheral
      arterial surgery (20 aspirin, 36 placebo). The relative risk of peripheral artery
      surgery in the aspirin group was 0.54 (95% confidence intervals 0.30-0.95; p =
      0.03). These data indicate that chronic administration of low-dose aspirin to
      apparently healthy men reduced the need for peripheral arterial surgery.

PMID- 1352569
TI  - Discounting health care: only a matter of timing?

PMID- 1352570
TI  - What happened to growth monitoring?

PMID- 1352571
TI  - Diagnosis of Sjogren's syndrome.

PMID- 1352572
TI  - Tripela wantaim.

PMID- 1352573
TI  - Low-molecular-weight heparin versus standard heparin in general and orthopaedic
      surgery: a meta-analysis.
AB  - Low-molecular-weight heparins (LMWHs) have theoretical advantages over standard
      heparin as postoperative thromboprophylactic agents. We conducted a meta-analysis
      of studies reported between 1984 and April, 1991, in which LMWHs were compared
      with standard heparin for postoperative prophylaxis. We included only randomised
      studies (reported in English, French, or German) in which investigators compared
      currently recommended doses of the agents and used adequate screening techniques
      for deep vein thrombosis. For all surgical studies the relative risk (LMWH versus
      standard heparin) for deep vein thrombosis was 0.74 (95% Cl 0.65-0.86), for
      pulmonary embolism 0.43 (95% Cl 0.26-0.72), and for major bleeding 0.98 (95% Cl
      0.69-1.40). Comparable relative risks were observed for the general and
      orthopaedic surgery studies separately. When the analysis for the general surgery
      studies was limited to those of strong methodology, assessed by eight criteria
      defined in advance, the benefit/risk ratio was less favourable--relative risk for
      deep vein thrombosis 0.91 (95% Cl 0.68-1.23), for major bleeding 1.32 (95% Cl
      0.69-2.56). There is at present no convincing evidence that in general surgery
      patients LMWHs, compared with standard heparin, generate a clinically important
      improvement in the benefit to risk ratio. However, LMWHs may be preferable for
      orthopaedic surgery patients, in view of the larger absolute risk reduction for
      venous thrombosis.

PMID- 1352574
TI  - Protein processing in lysosomes: the new therapeutic target in neurodegenerative
      disease.
AB  - A little recognised feature of neurons is their large complement of lysosomes.
      Studies of the accumulation of the abnormal isoform of the prion protein (PrPSC)
      in the prion encephalopathies and the formation of beta/A4 protein from its
      precursor in Alzheimer's disease suggest that generation of these key proteins
      takes place in lysosome-related organelles. The release of hydrolytic enzymes
      from lysosomes may be a primary cause of neuronal damage. Although molecular
      genetic approaches have identified protein mutations central to the main
      neurodegenerative disease, cell biological observations are now beginning to
      unravel the intracellular pathways involved in the molecular pathogenesis of
      neurodegeneration: as a result, it is now appropriate to consider therapeutic
      manipulation of the lysosomal system as an approach to treatment.

PMID- 1352575
TI  - Primary aldosteronism: hypertension with a genetic basis.
AB  - Exciting developments in knowledge of primary aldosteronism include description
      of new subtypes and elucidation of the genetic basis of one variety. Furthermore,
      relatively simple biochemical screening (aldosterone/renin ratio) has disclosed
      that primary aldosteronism is more common than previously thought, by diagnosing
      patients at an earlier, normokalaemic stage. The mutant gene discovered in the
      glucocorticoid-suppressible variety (FHI) codes for an aldosterone biosynythetic
      enzyme normally controlled by angiotensin II, and now controlled by
      corticotropin. The zona fasciculata is hyperplastic and makes aldosterone and
      "hybrid steroids" 18-oxocortisol and 18-hydroxycortisol in excess, in response to
      ACTH but not to angiotensin II. Adrenal tumours have not yet been described in
      this condition. Aldosterone-producing adenomas (Conn's syndrome) are also
      commonly composed of zona fasciculata-like cells, make "hybrid steroids" in
      excess and are very sensitive to ACTH but not to angiotensin II. We have
      described a new variety of aldosterone-producing adenoma which is responsive to
      angiotensin II (AII-responsive APA), consists of at least 20% zona glomerulosa
      like cells, and does not make "hybrid steroids" in excess. We have also described
      a new familial variety of primary aldosteronism that includes tumours and is not
      glucocorticoid-suppressible (FHII). We propose that primary aldosteronism is a
      spectrum of genetic diseases expressed as either hyperplasia or neoplasia, and
      that morphological and genetic diversity explains biochemical and clinical
      behaviour.

PMID- 1352576
TI  - Should antianginal medication be stopped for exercise testing?

PMID- 1352577
TI  - Diet and cancer: causal relation or just wishful thinking?

PMID- 1352578
TI  - Health, but not for all.

PMID- 1352579
TI  - Consent, refusal, and minors.

PMID- 1352580
TI  - Life-threatening reaction after viper bite: detection of venom-specific IgE by
      dot assay.

PMID- 1352581
TI  - ECG recording direct to personal computer.

PMID- 1352582
TI  - Surface coil magnetic resonance imaging of the fetal brain.

PMID- 1352583
TI  - Public health consequences of the civil war in Somalia, April, 1992.

PMID- 1352584
TI  - Emergence in Ontario, Canada, of multiresistant Salmonella typhi from South Asia.

PMID- 1352585
TI  - Vitamin A deficiency and childhood mortality.

PMID- 1352586
TI  - Asthma and wheezing.

PMID- 1352587
TI  - From nose to mouth in breathlessness.

PMID- 1352588
TI  - Ophthalmological screening for CMV retinitis in HIV infection.

PMID- 1352589
TI  - Potentially hazardous compound in a herbal slimming remedy.

PMID- 1352590
TI  - Use of nonoxynol-9.

PMID- 1352591
TI  - Medical training in France.

PMID- 1352592
TI  - Obstetrics in developing countries.

PMID- 1352593
TI  - Treatment of refugees in European countries of asylum.

PMID- 1352594
TI  - Influence of The Lancet on chorionic villus sampling.

PMID- 1352595
TI  - Employment of disabled people.

PMID- 1352596
TI  - The commercial pyramid.

PMID- 1352597
TI  - Debrisoquine 4-hydroxylase (CYP2D) locus and possible susceptibility to
      schizophrenia.

PMID- 1352598
TI  - Intravenous immunoglobulin treatment in multifocal motor neuropathy.

PMID- 1352599
TI  - Ophthalmic artery velocimetry in pregnant women.

PMID- 1352600
TI  - Accelerated progression of renal function loss after two pregnancies in a patient
      with proteinuria.

PMID- 1352601
TI  - 2,8-Dihydroxyadenine crystalluria vs urolithiasis.

PMID- 1352602
TI  - Increased oxygen and exercise performance in chronic heart failure.

PMID- 1352603
TI  - Favourable outcome after plasmapheresis for vincristine overdose.

PMID- 1352604
TI  - Ondansetron in carcinoid syndrome.

PMID- 1352605
TI  - Idarubicin cardiotoxicity in acute myeloid leukaemia.

PMID- 1352606
TI  - Preliminary diagnosis of Parkinson's disease by olfactory bulb pathology.

PMID- 1352608
TI  - Destructive effect of prolonged autoclaving of blood specimens in Guthrie test.

PMID- 1352609
TI  - Efficacy of perioperative nutritional support.

PMID- 1352607
TI  - Primary gastric lymphoma and occupational exposures.

PMID- 1352610
TI  - Chlamydia trachomatis and wheezing.

PMID- 1352611
TI  - Regulation of somatostatin synthesis by GABAA receptor stimulation in mouse
      brain.
AB  - Neuroanatomical data have documented the existence of synaptic contacts between
      gamma-aminobutyric acid (GABA) terminals and periventricular hypothalamic
      somatostatin (SRIF) neurons. In other brain regions, like the cortex or
      hippocampus, GABA and SRIF are colocalized in short interneurons. These
      observations suggest that GABA modulates SRIF neuronal activity. In order to test
      this hypothesis, we studied the effects of the in vivo stimulation of the GABAA
      receptor (muscimol, 0.75 mg/kg + diazepam, 2.5 mg/kg) on SRIF content and
      preproSRIF mRNA levels, in mouse brain. Chronic (7 days), but not acute,
      treatment induced a 38% decrease in hypothalamic SRIF content (as estimated by
      RIA), a 20% decrease in cortex and no effect in the striatum. The decrease in
      hypothalamic and cortical SRIF levels lasted until 24 h after cessation of the
      treatment. In the hypothalamus, prosomatostatin mRNA levels were estimated by
      Northern blot analysis using a 32P-labeled 45-mere oligoprobe. ProSR1F mRNA
      hypothalamic levels were equally (48%) decreased by the acute and chronic
      treatments and remained lower than controls 48 h after the last injection.
      Quantitative in situ hybridization was used to examine the regional distribution
      of GABA-induced acute inhibition of proSR1F mRNA densities, using the same
      oligomere labeled with 35S. ProSR1F mRNA levels were decreased by 35% in the
      periventricular hypothalamic nucleus. In contrast, no significant modification
      was observed in cortex, striatum and hilus of the dentate gyrus of the dorsal
      hippocampus. The present data demonstrate a regionally selective inhibitory
      action of GABA, mediated by GABAA receptors stimulation, on the biosynthetic
      mechanisms of the long projecting neuroendocrine SRIF neurons of the anterior
      periventricular nucleus of the hypothalamus.

PMID- 1352612
TI  - Ethanol blocks the cold-induced increase in thyrotropin-releasing hormone mRNA in
      paraventricular nuclei but not the cold-induced increase in thyrotropin.
AB  - The effects of a single intraperitoneal injection of ethanol (3 g/kg b.wt.) on
      the hypothalamic-pituitary-thyroid system was explored as a possible explanation
      of the hypothermic effect of ethanol. Serum thyroid hormones were significantly
      reduced by ethanol injection, but ethanol did not affect the cold-induced
      increase in serum thyroid hormones or thyroid-stimulating hormone (TSH). Since
      cold-exposure stimulates serum levels of TSH and thyroid hormones by stimulating
      thyroid-releasing hormone (TRH) release from neurons of the PVN, these findings
      demonstrate that ethanol did not block pituitary response to TRH or thyroid
      response to TSH. Paradoxically, ethanol increased cellular levels of TRH mRNA in
      the paraventricular nucleus (PVN), and blocked the cold-induced increase in TRH
      mRNA, suggesting that ethanol uncouples the regulation of TRH gene expression
      from the regulation of TRH release specifically in neurons of the PVN.
      Measurements of the effects of ethanol on TRH mRNA in thalamus, and beta-actin,
      vasopressin, somatostatin and corticotropin-releasing hormone (CRH) mRNAs in the
      PVN in addition to TRH mRNA revealed very specific effects of ethanol on the TRH
      neuronal system.

PMID- 1352613
TI  - Dopamine transporter mRNA: dense expression in ventral midbrain neurons.
AB  - Oligonucleotides and a full-length cDNA encoding a functional dopamine
      transporter (DAT1) hybridize to a 3.7 kb mRNA that is concentrated in mRNA
      prepared from midbrain and absent in specimens from cerebellum or cerebral
      cortex. In situ hybridization reveals substantial hybridization densities
      overlying neurons of the substantia nigra, pars compacta, and the parabrachialis
      pigmentosus region of the ventral tegmental area (VTA). Neurons in the linear and
      paranigral VTA regions display lower levels of expression. Preliminary studies in
      arcuate neurons suggest modest hybridization. Different dopaminergic cell groups
      display different levels of DAT1 dopamine transporter expression.

PMID- 1352614
TI  - Working group on noncoronary cardiovascular disease and exercise in women.

PMID- 1352615
TI  - Involvement of a possible chaperonin in the efficient expression of a cloned
      CryIIA delta-endotoxin gene in Bacillus thuringiensis.
AB  - The Bacillus thuringiensis cryIIA delta-endotoxin gene is found as the third-gene
      in a three-gene operon, with a sporulation-dependent promoter lying upstream of
      the first gene, orf1. We show here that the polypeptide product of the middle
      gene (orf2) is required for efficient expression of the toxin gene. In the
      absence of a functional ORF2 polypeptide the toxin does not form the crystalline
      inclusions characteristic of other known Bacillus thuringiensis toxins. We
      discuss the importance of this finding with respect to the possible role of
      chaperonins in the crystallization of these proteins.

PMID- 1352616
TI  - GroEL proteins from three Pseudomonas species.

PMID- 1352617
TI  - Report of the proceedings of the 26th conference of the Council for International
      Organisation of Medical Sciences, WHO Headquarters, Geneva, Switzerland, 5-7
      February, 1992.

PMID- 1352618
TI  - The vasa vasorum and the paradox of beta-blocker therapy.
AB  - The use of beta-blockers in the treatment of angina, claudication or hypertension
      is a therapeutic paradox. All those conditions feature increased constrictor
      tone, so it appears to make little sense to treat them with drugs which block the
      action of vasodilators. The paradox would disappear, however, if vasodilators
      could be shown to have the ability to increase constrictor tone in certain
      circumstances. This paper argues that they have. It presents evidence that
      isoprenaline, a potent dilator of the dog's saphenous vein, is a powerful
      constrictor of the vein when it is released from the vasa vasorum of the vein.
      Indeed, on a molar basis, it appears to be a more powerful constrictor of the
      vein than exogenous noradrenaline is. Since there is no reason to suppose that
      isoprenaline is unique among dilators in demonstrating this type of bimodal
      behaviour, it is possible to justify the proposal that compounds which are
      normally classified as endogenous dilators may, when released from the
      pathological vasa vasorum which neoproliferate in atherosclerosis, be responsible
      for the constrictor effects associated with claudication, and some forms of
      hypertension and angina. If true then beta-blockade would not be a paradoxical
      choice of treatment for those conditions.

PMID- 1352619
TI  - Management of a major box jellyfish (Chironex fleckeri) sting. Lessons from the
      first minutes and hours.
AB  - OBJECTIVE: To report the management of a serious box jellyfish (Chironex
      fleckeri) envenomation from the first minutes of bystander first aid and
      treatment by ambulance personnel to subsequent treatment in hospital. CLINICAL
      FEATURES: A 14-year-old girl sustained a serious Chironex fleckeri sting. There
      was no loss of consciousness, but the patient suffered severe pain, myocardial
      irritability, acute pulmonary oedema and mild systemic hypotension, due to the
      direct toxic effects of the venom. Thirst was a dominant symptom. INTERVENTION
      AND OUTCOME: Management involved rapid bystander action and call for ambulance
      assistance; and early intervention with oxygen/nitrous oxide administration,
      compression bandaging, antivenom administration and electrocardiographic
      monitoring at the site by ambulance personnel. Echocardiography in hospital three
      hours after the sting showed a normal myocardium. In hospital management resulted
      in recovery. Nocturnal itching of the sting persisted for six weeks. CONCLUSIONS:
      (i) Vinegar dousing may irritate freshly stung skin, but as a nematocyst
      inhibitor vinegar remains an essential part of the first aid treatment for
      cubozoan jellyfish stings. (ii) Compression/immobilisation bandaging was not
      associated with long-term harm to the sting area. (iii) The pain of an
      intramuscular antivenom injection may not be felt by a chirodropid sting victim,
      so safe injection protocols must be strictly observed. (iv) Ambulance services in
      other States whereas there is a risk of box jellyfish (Chironex fleckeri or
      Chiropsalmus quadrigatus) stings should be similarly trained and equipped to deal
      with serious jellyfish envenomations.

PMID- 1352620
TI  - Bon appetit.

PMID- 1352621
TI  - Tourette's syndrome.

PMID- 1352622
TI  - Major depressive disorder.

PMID- 1352623
TI  - Biological correlates of impulsive disruptive behavior disorders: attention
      deficit hyperactivity disorder, conduct disorder, and borderline personality
      disorder.

PMID- 1352625
TI  - Future directions in neuroscience research for twentieth-century child and
      adolescent psychiatry.

PMID- 1352624
TI  - Childhood-onset schizophrenia.

PMID- 1352626
TI  - Biochemistry and pathophysiology of diabetes. Proceedings of conference on
      pathophysiology and treatment of diabetes mellitus. 1990.

PMID- 1352628
TI  - Characterization of 3-carboxy-5-phosphono-1,2,3,4-tetrahydroisoquinoline (SC
      48981), a potent competitive N-methy-D-aspartate (NMDA) receptor antagonist, in
      vitro and in vivo.
AB  - (+/-)-3-Carboxy-5-phosphono-1,2,3,4-tetrahydroisoquinoline (SC-48981), a
      conformationally restricted analog of the potent competitive N-methyl-D-aspartate
      (NMDA) antagonist, 2-amino-5-phosphonopentanoate (AP-5), potently inhibited the
      binding of [3H]glutamate to the N-methyl-D-aspartate (NMDA) receptors with a Ki
      of 1.6 mcM, but with minimal affinity for kaininate and quisqualate receptors (Ki
      greater than 50 mcM), in vitro. Consistent with its ability to antagonize the
      NMDA receptor, SC-48981 decreased the binding of [3H]glycine and [3H]TCP [1-(2
      thienyl)cyclohexylpiperidine] to the NMDA-associated glycine and phencyclidine
      (PCP) recognition sites, in vitro. SC-48981 attenuated levels of basal cGMP and
      harmaline-induced increases in levels of cGMP in the mouse cerebellum, in vivo,
      in a competitive manner, with ED50 values of 5.5 and 8.7 mg/kg, i.p. Direct
      intracerebellar injection of SC-48981 (0.5 microgram) attenuated increases in
      levels of cGMP induced by central injection of the NMDA-associated glycine
      receptor agonist, D-serine and by NMDA itself. Parenteral administration of SC
      48981 (25 mg/kg, s.c.) decreased basal levels of cGMP for up to 3 h. These
      results indicate that SC-48981 represents a novel bioavailable competitive NMDA
      antagonist with a long duration of action.

PMID- 1352629
TI  - Carbamazepine-induced neurotoxicity and its prevention by NMDA in cultured
      cerebellar granule cells.
AB  - Long-term neurotoxicity of carbamazepine was studied in cultured cerebellar
      granule cells. Treatment of cells with carbamazepine for 3 days induced a dose
      dependent neurotoxicity detected by a loss of [3H]ouabain binding to Na+,K(+)
      ATPase, and [3H]N-methyl scopolamine binding to muscarinic cholinergic receptors
      as well as by direct morphologic examination. NMDA protected against
      carbamazepine-induced toxicity and this protection was blocked by 2-amino-5
      phosphono-valerate (APV). The neurotoxicity induced by carbamazepine may be
      involved in the teratogenic and adverse effects of overdose associated with the
      treatment of manic-depressive illness and seizures.

PMID- 1352627
TI  - 7th IPEG Symposium. Boca Raton, Florida, May 23-25, 1992. Abstracts.

PMID- 1352630
TI  - Induction of giant depolarizing potentials by zinc in area CA1 of the rat
      hippocampus does not result from block of GABAB receptors.
AB  - The possibility that zinc (Zn2+) induces giant depolarizing potentials (GDPs) by
      blocking pre- and postsynaptic gamma-aminobutyric acidB (GABAB) receptors in area
      CA1 of rat hippocampal slices was investigated. Monosynaptic GABAA receptor
      mediated fast and GABAB receptor-mediated late inhibitory postsynaptic potentials
      (IPSPs) were evoked in the presence of the excitatory amino acid (EAA) receptor
      antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-amino-5
      phosphonovalerate (APV). Addition of Zn2+ (0.3 mM) resulted in the appearance of
      long-lasting GDPs which obscured monosynaptic late IPSPs. The GABAA receptor
      antagonist bicuculline methiodide (BMI; 30 microM) blocked fast monosynaptic
      IPSPs and GDPs, revealing a monosynaptic late IPSP that was prolonged in the
      presence of Zn2+ and blocked by the GABAB receptor antagonist CGP 35,348 (100
      microM). The selective GABAB receptor agonist baclofen (10 microM) depressed
      monosynaptic IPSPs and population excitatory postsynaptic potentials (pEPSPs) by
      acting at presynaptic GABAB receptors. Depression of synaptic potentials by
      baclofen was unaffected by Zn2+. These results suggest that induction of GDPs in
      area CA1 does not result from an action of Zn2+ at GABAB receptors. We suggest
      instead that Zn2+ induces GDPs by inducing synchronized discharge of GABAergic
      interneurons.

PMID- 1352631
TI  - Cat retinal ganglion cells show transient responses to acetylcholine and
      sustained responses to L-glutamate.
AB  - The neuropharmacological basis for the different receptive field properties of
      cat retinal ganglion cells was investigated using whole cell voltage-clamp
      recordings from acutely dissociated adult tissue. Subclasses of physiologically
      characterised ganglion cells were determined on the basis of (i) their soma
      diameters and (ii) their projection to central visual nuclei (identified by
      microinjection of fluorescent dyes into the lateral geniculate and/or superior
      colliculus). The sensitivities of all categories of ganglion cells, prepared from
      peripheral retina were found to be similar for gamma-amino butyric acid, glycine,
      acetylcholine and glutamate. The kinetics of desensitisation differed among
      receptor subtypes, revealing possible physiologically significant molecular
      specialisations that could be involved in shaping synaptic transmission.

PMID- 1352632
TI  - Selectivity of Thy-1 monoclonal antibodies in enhancing neurite outgrowth.
AB  - Thy-1 monoclonal antibodies (MAbs) have previously been shown to promote neurite
      outgrowth from retinal ganglion cells and a variety of other neurons. We have
      studied the effect on neurite outgrowth of several Thy-1 MAbs with quantitatively
      similar binding properties and found that only certain Thy-1 MAbs promote neurite
      outgrowth. This finding suggests that the antibody effects depend on specific
      interactions with one or more active sites on the Thy-1 glycoprotein.

PMID- 1352633
TI  - Concomitant increases in the extracellular concentrations of excitatory and
      inhibitory amino acids in the rat hippocampus during forebrain ischemia.
AB  - The extracellular concentrations of aspartate, glutamate, glutamine, taurine and
      gamma-aminobutyric acid in the hippocampus were determined during and after
      forebrain ischemia (4-vessel model) in the unanaesthetized rat. Ischemia led to a
      large increase in both inhibitory (taurine and gamma-aminobutyric acid) and
      excitatory amino acids (aspartate, glutamate). These results suggest that in this
      model, as previously proposed in other models of ischemia, the large increase of
      inhibitory amino acids could counterbalance the excitotoxicity due to aspartate
      and glutamate.

PMID- 1352634
TI  - Finding freedom from the frightful fidgets.

PMID- 1352635
TI  - Maternal antibodies in N'Dama calves kept under natural trypanosomiasis risk in
      The Gambia.

PMID- 1352636
TI  - Assistants-at-surgery: recognition of the role of the registered nurse.
AB  - In the Omnibus Budget Reconciliation Act of 1989 (OBRA '89), Congress directed
      the Physician Payment Review Commission (PPRC or "the Commission") to make
      recommendations on payment policies for assistants-at-surgery, including
      physicians, physician assistants (PAs) and registered nurses (RNs). The National
      Association of Orthopaedic Nurses (NAON), via the Government Relations Committee
      and Executive Board, participated in the public hearing on this issue and
      submitted testimony on the role of the RN first assistant during orthopaedic
      surgery. In its 1991 report to Congress, the Commission recommended that
      inappropriate utilization of assistants-at-surgery could be reduced by
      implementing "profiling"--a variety of techniques to examine the use of
      assistants. PPRC failed to comment on policies related to non-physician
      providers, determining that this was a coverage issue, not a payment issue and
      thus outside the scope of their jurisdiction. However, as global surgical payment
      policy is further defined by the Health Care Financing Administration (HCFA) and
      Congress, consideration will again be given to incorporating payment for
      assistants-at-surgery into a comprehensive fee schedule. Recognition of the
      registered nurse as an assistant-at-surgery will continue to be a primary goal of
      NAON.

PMID- 1352638
TI  - Involvement of neurotransmitters in the nucleus tractus solitarii in
      cardiovascular regulation.

PMID- 1352637
TI  - Modulation of neurotransmission in airways.

PMID- 1352639
TI  - [An unusual association: panarteritis nodosa and rheumatoid arthritis as an
      overlapping collagenous syndrome].
AB  - The clinical record of a woman with two connective tissue diseases is presented.
      It started as a necrotizing arteritis with hepatic involvement and chronic
      multineuritis consistent with PAN. After a long period of clinical evolution the
      patient developed a real rheumatoid arthritis with positive RF. This clinical
      picture overlapped clinically and serologically the former one. A good response
      to the steroid therapy and a careful follow-up permitted a satisfactory life to
      this patient for about ten years.

PMID- 1352640
TI  - [Bladder neoplasm in a patient with panarteritis nodosa treated with
      cyclophosphamide].
AB  - Cyclophosphamide is used both in the treatment of malignant and non-malignant
      diseases. Urinary neoplasms secondary to its use have been described. We discuss
      the case of a patient with panarteritis nodosa treated with cyclophosphamide
      during 63 months, with a total dose of 210 grams, and that showed a bladder
      neoplasm 8 years after beginning of the treatment. In patients receiving a total
      dose of cyclophosphamide over 85 grams, a follow-up of ten years minimum should
      be performed aimed to the early detection of secondary neoplasms.

PMID- 1352641
TI  - [The long-term treatment of Takayasu's disease with cyclosporin].

PMID- 1352642
TI  - Epidemiology in Occupational Health. 8th International Symposium. Paris,
      September 10-12, 1991. Papers and Abstracts.

PMID- 1352643
TI  - [Anesthesia 92. Barcelona, 7-12 June 1992. Abstracts].

PMID- 1352644
TI  - [Anesthesia 92. Barcelona, 7-12 June 1992. Abstracts].

PMID- 1352645
TI  - Inhibition of fibroblast proliferation in L-valine reduced selective media.
AB  - A selective cell culture medium, D-valine minimal essential medium (92 mg/l), has
      been developed to inhibit the proliferation of fibroblasts in cell culture
      (Gilbert & Migeon 1975). Substitution of D-valine for L-valine prevents
      fibroblast growth due to the absence of D-amino acid oxidase in these cells. Most
      cell cultures require foetal bovine serum as an essential component of the
      culture media, however foetal bovine serum contains L-valine, negating the value
      of D-valine selective media. To overcome this difficulty, we have produced a
      modified selective media for cell culture, by the dialysis of foetal bovine serum
      and confirmed its ability to inhibit fibroblast growth whilst still allowing the
      proliferation of epithelial cells in culture.

PMID- 1352648
TI  - [The 1991 International Congress of the Association Dentaire Francaise. Interview
      by Michel Perrier].

PMID- 1352646
TI  - Effectiveness of alpha 2-adrenergic receptor stimulation in reducing the central
      toxicity following cholinesterase inhibition.
AB  - Previous studies in this laboratory have demonstrated that the centrally-acting
      alpha 2-adrenergic agonist clonidine can offer significant protection against
      both the acute and chronic toxicity following irreversible cholinesterase
      inactivation with soman. The purpose of this study was to estimate the
      contribution of central mechanisms to soman toxicity in a rat model; and to
      determine the effectiveness of clonidine and a series of related agonists to
      offer protection against the acute and chronic manifestations of this toxicity.
      To investigate the central component of soman toxicity, animals were pretreated
      with the peripherally selective reversible cholinesterase inhibitor
      pyridostigmine, a standard protective agent. Pyridostigmine pretreatment resulted
      in significant improvement in survival following soman administration. However,
      pyridostigmine was not able to inhibit the signs of central soman toxicity,
      including convulsive behavior. Clonidine and several related drugs produced both
      a further reduction in lethality and a significant reduction in the central signs
      of soman toxicity. Signs of delayed toxicity to soman were apparent in rats
      surviving 48 h after administration as measured in open-field locomotor
      monitoring. Again, pyridostigmine did not offer protection against such delayed
      toxicity. When clonidine was included in the regimen, however, significant
      improvement in performance in this measure was observed. These results are
      consistent with our earlier findings of significant protection provided by
      clonidine and related drugs against acute and chronic manifestations of soman
      toxicity and provide further evidence that 1) central toxicity is an important
      contributor to soman's actions, and 2) stimulation of central alpha 2-adrenergic
      receptors limits the expression of this central toxicity.

PMID- 1352647
TI  - Role of diethylnitrosamine, 2-acetylaminofluorene and partial hepatectomy in the
      expression of glutathione-S-transferase-P and gamma-glutamyltranspeptidase in the
      early steps of rat liver carcinogenesis.
AB  - Three factors involved in the Solt and Farber model of rat liver carcinogenesis
      were studied alone and in various combinations: diethylnitrosamine (DEN)
      initiating dose, 2-acetylaminofluorene (2-AAF) feeding and partial hepatectomy.
      The administration of DEN alone (200 mg/kg) was able to switch on glutathione-S
      transferase, placental type (GST-P) expression 3 weeks later at a low level (85
      U/micrograms protein) which was stable for 10 weeks in the absence of
      histopathological lesions. During the same time, gamma-glutamyl transpeptidase
      (GGT) activity presented 2 waves of increase. The feeding of 0.03% 2-AAF for 2
      weeks appeared as a determinant factor in the expression of GST-P protein as well
      as GGT induction (15- and 7-fold versus DEN alone, respectively). The addition of
      partial hepatectomy enhanced again GST-P expression (1.5-fold) and GGT induction
      (2-fold). However, GST-P foci increased in size, not in number while GGT foci
      increased both in size and in number. These data indicated that 2-AAF was a
      crucial component of the selection procedure since partial hepatectomy alone,
      with or without DEN initiation was inefficient in promoting GST-P expression.
      Therefore, 2-AAF would be able to promote the growth of GST-P-positive cells
      initiated by DEN, a mechanism likely responsible for its tumor-promoting effect.

PMID- 1352649
TI  - [The current status of complete ceramic restoration methods].

PMID- 1352650
TI  - [The interface, OP methods. Processes at the interface of implant and implant
      bed. System-specific operational methods].

PMID- 1352651
TI  - [Oral implantology for the dental office].

PMID- 1352652
TI  - [Advancements in the diagnosis and therapy of prostate neoplasms. International
      symposium Enantone/Prostop (Leuprorelin-Depot). Hamburg, 7 March 1992].

PMID- 1352654
TI  - [Effects of MPTP on the mouse retina].
AB  - MPTP is known as a selective neurotoxin which destroys dopamine-containing
      neurons, and induces a model of Parkinson's disease. In the retina, MPTP acts on
      the amacrine cells which contain dopamine. In the present study, C57BL/6J mice
      were treated i.p. with MPTP (cumulative dose, 150 mg/kg), and the role of
      dopamine in the mouse retina was investigated electrophysiologically and
      immunohistochemically. ERGs were recorded before and 10, 30 and 50 days after
      MPTP injection. The amplitude of the oscillatory potentials was greatly reduced,
      and that of the b-wave to a lesser degree, while the a-wave was slightly reduced
      10 days after injection. These ERG changes tended to return to the control level
      50 days after injection. Immunohistochemical analysis showed that 10 days after
      MPTP injection the number of tyrosine hydroxylase positive amacrine cells was
      reduced by approximately 50%, and that these changes had lasted at least until 50
      days after MPTP injection.

PMID- 1352653
TI  - Biological activity of subfractions from scrapie-associated fibrils.
AB  - Subfractions, a nucleic acid fraction and a PrP fraction consisting of PrP17-25,
      a core fragment of PrPsc, were prepared from the scrapie-associated fibril
      enriched fraction from scapie-affected mouse brains. The nucleic acid fraction
      consisted mainly of variously fragmented DNA and no scrapie-specific nucleic acid
      was detected in the fraction by SDS polyacrylamide gel electrophoresis. To
      examine the biological activity, the nucleic acid fraction was either first
      introduced into mouse L-929 cells before or after nuclease treatments, then
      transfected cell lysates prepared 2 weeks later were inoculated into mice, or
      directly inoculated into mice with or without the PrP fraction. The PrP fraction
      alone was also inoculated into mice. Mice inoculated with the transfected cell
      lysates or with the nucleic acid fraction alone showed no scrapie signs during
      their lifespan or the observation period. While 60% of the mice inoculated with
      the PrP fraction alone and 67% of those inoculated with the fraction together
      with the nucleic acid fraction showed clinical signs of scrapie. A nucleic acid
      molecule bound covalently to PrP17-25 was not detected. The results obtained by
      the present procedures so far suggest scrapie infectivity to be associated with
      PrPsc, which does not contain any detectable scrapie-genome molecule as either
      free or covalently bound nucleic acid.

PMID- 1352655
TI  - A Symposium: Management of Heat Failure in the 1990s: A Reassessment of the Role
      of Digoxin Therapy. New York, New York, July 27-28, 1991.

PMID- 1352656
TI  - Current status of non-digitalis positive inotropic drugs.
AB  - Considerable effort and resources have been directed at the development and study
      of positive inotropic drugs over the past 10-15 years. Much has been learned
      about the physiology and pharmacology of myocardial contraction, the application
      of agents to augment contractility, and, importantly, the general and specific
      limitations of positive inotropic therapy. Studies on acute inotropic
      intervention have now shown that a drug's ability to augment overall cardiac
      performance is heavily dependent on its effects on vasculature, vascular control,
      and ventricular-vascular coupling. The clinical research on new agents has served
      to remind us how difficult it is to formulate the "ideal" positive inotropic or
      cardiovascular support drug for the critical care setting. The vast effort to
      develop a chronically and orally administrable drug to replace or even supplement
      digitalis has generally been disappointing. The dopaminergic agents (e.g.,
      ibopamine, levodopa) act primarily via vasodilation and their effectiveness and
      role in managing heart failure remain unresolved. The initial excitement about
      the phosphodiesterase III inhibitors (e.g., amrinone, milrinone, enoximone) has
      been tempered by the results of large well-designed trials indicating variable
      effectiveness and a prominent adverse effect profile. During long-term oral
      administration none of these agents has been shown to improve clinical status or
      exercise capacity beyond that achieved by digoxin, when administered either
      separately or in combination with digoxin. The Prospective Randomized Milrinone
      Survival Evaluation (PROMISE) trial, showing that repeated oral administration of
      milrinone can increase mortality in heart failure, is having a devastating effect
      on the further development of this class of drugs.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1352657
TI  - Redefining the role of digoxin in the treatment of atrial fibrillation.
AB  - Atrial fibrillation (AF) encompasses a variety of discrete clinical syndromes,
      including paroxysmal, chronic, acute, and postoperative. Digoxin, long considered
      the mainstay of therapy for rate control in all types of AF, appears to have only
      modest electrophysiologic effects, which are mediated primarily by the autonomic
      nervous system. Digoxin has less potency than the calcium antagonists or beta
      blocking drugs with respect to atrioventricular nodal blockade. Although less
      potent than calcium antagonists or beta-blocking drugs on the atrioventricular
      node, digoxin provides positive inotropic support, whereas the other 2 agents can
      suppress left ventricular function. Thus, digoxin is the agent of choice in
      patients with AF in the setting of significant left ventricular dysfunction.
      However, in the absence of left ventricular dysfunction, digoxin should be
      considered second-line therapy for the treatment of all AF syndromes.

PMID- 1352659
TI  - The Rett Syndrome. Symposium of the Joint Convention of the 5th International
      Child Neurology Congress and the 3rd Asian and Oceanian Congress of Child
      Neurology. Tokyo, November 4-9, 1990.

PMID- 1352658
TI  - Beta-adrenergic blockade for the treatment of hyperthyroidism.
AB  - PURPOSE: To review the clinical and biochemical effects of beta-adrenergic
      blocking drugs on hyperthyroidism. MATERIALS AND METHODS: Studies published since
      1972 were identified through a computerized search of MEDLINE and extensive
      searching of the bibliographies of the articles identified. Based on an
      understanding of the differences in beta-blocker metabolism in euthyroid and
      hyperthyroid patients, we reviewed the differences in pharmacokinetics and
      metabolic and clinical outcomes during their use in hyperthyroidism, as reported
      in the articles reviewed. RESULTS: beta Blockers have been used to modify the
      severity of the hyperadrenergic symptoms of hyperthyroidism for the past 20
      years. The clinical efficacy of these agents is affected by hyperthyroid-induced
      alterations in their gastrointestinal absorption, hepatic metabolism, and renal
      excretion. The mechanisms whereby these clinical changes are effected is unknown.
      The agents differ in their beta 1 cardioselectivity, membrane-stabilizing
      activity, intrinsic sympathomimetic activity, and lipid solubility. They do not
      appear to alter synthesis or secretion of thyroid hormone by the thyroid gland.
      Their effects on thyroxine metabolism are contradictory. Decreased thyroxine to
      triiodothyronine conversion is caused by some, but not all, beta blockers, and
      this appears to correlate with membrane-stabilizing activity. There does not
      appear to be any alteration in catecholamine sensitivity during beta-adrenergic
      blockade. CONCLUSIONS: The principal mechanism of action of beta blockers in
      hyperthyroidism is to antagonize beta-receptor-mediated effects of
      catecholamines. beta Blockers are effective in treating hypermetabolic symptoms
      in a variety of hyperthyroid states. Used alone, they offer significant
      symptomatic relief. They are also useful adjuvants to antithyroid medications,
      surgery, and radioactive iodide treatment in patients with Graves' disease and
      toxic nodular goiters.

PMID- 1352661
TI  - International Society for Biomedical Research on Alcoholism, 6th Congress.
      Bristol, England, June 21-27, 1992. Abstracts.

PMID- 1352660
TI  - Classical genetic analyses of responses to sedative-hypnotic drugs in crosses
      derived from long-sleep and short-sleep mice.
AB  - A classical (Mendelian) genetic analysis of responses to eight sedative-hypnotic
      compounds (ethanol, urethane, trifluoroethanol, chloral hydrate, barbital,
      paraldehyde, methyprylon, pentobarbital) was conducted in crosses derived from
      mouse lines that were selectively bred for differential duration of anesthesia
      following ethanol. The sleep-time responses of these mice, the long-sleep (LS)
      and short-sleep (SS) mouse lines, as well as the F1, F2 and backcross (F1 x LS,
      F1 x SS) generations were measured. Generally, differences in responses among the
      generations were greater for water soluble compounds than were differences for
      more lipid soluble compounds. Also, the inheritance of responses to water soluble
      compounds could be explained primarily by additive effects of alleles while the
      inheritance patterns for more lipid soluble compounds were more complex. Genetic
      correlation with ethanol response decreased with increasing lipophilicity. These
      results suggest that the selection of the LS-SS mouse lines was specific for
      water soluble anesthetic agents. Because several of these agents are known to act
      at GABA receptors, examination of the interactions of compounds which differ in
      lipid solubility at GABA receptors from LS and SS mice may prove useful in
      elucidating the mechanism of the anesthetic actions of ethanol and other drugs.

PMID- 1352662
TI  - Circulatory responses during electroconvulsive therapy. The comparative effects
      of placebo, esmolol and nitroglycerin.
AB  - Electroconvulsive therapy is usually accompanied by activation of the autonomic
      nervous system, which may be harmful in patients with cerebrovascular or
      ischaemic heart disease. We have compared this haemodynamic response in a series
      of 82 electroconvulsive treatments randomly assigned to receive either
      nitroglycerin 3 micrograms.kg-1, esmolol 2 mg.kg-1 or placebo. These drugs were
      given shortly after the suxamethonium and 2 min before the electroconvulsive
      therapy in all cases. Heart rate was significantly lower with esmolol 1 min after
      therapy as was blood pressure (systolic and diastolic). The pulse rate was higher
      following nitroglycerin than placebo, which in turn was higher than esmolol. The
      three groups did not differ with regard to seizure duration. The results
      demonstrate that esmolol is more effective than nitroglycerin in controlling the
      haemodynamic response to electroconvulsive therapy. With recent emphasis on
      stabilisation of heart rate in preference to blood pressure in at-risk cardiac
      patients, our study suggests that, in the doses selected, esmolol is preferred to
      nitroglycerin to control the heart rate response to electroconvulsive therapy.

PMID- 1352663
TI  - An atypical case of immunodeficiency.

PMID- 1352664
TI  - Diagnostic implications of detection of proteinase K-resistant protein in spleen,
      lymph nodes, and brain of sheep.
AB  - Brain, spleen, and selected lymph nodes from sheep with clinical signs of scrapie
      were analyzed for presence of proteinase K-resistant protein (PrP-res). Diagnosis
      of scrapie on the basis of detection of PrP-res was compared with diagnosis on
      the basis of histologic evaluation of the brain from clinically affected or
      exposed sheep. Proteinase K-resistant protein was found in every brain that was
      histologically positive for scrapie, and in addition, was found in the brain of
      several clinically positive sheep that were not diagnosed as scrapie-positive by
      histologic evaluation. Proteinase K-resistant protein was also found in 87% of
      the spleens and lymph nodes from sheep that had PrP-res detected in brain
      homogenates. Therefore, analysis of sheep brain, spleen, or lymph nodes for PrP
      res provided a diagnostic approach that was superior to histologic examination
      alone for detection of naturally scrapie agent-infected sheep.

PMID- 1352666
TI  - Effects of broxaterol and theophylline on fatigued canine diaphragm in vivo. A
      randomized, controlled study.
AB  - Since broxaterol, a new beta 2-agonist, has been shown to improve contractility
      of fatigued canine diaphragm in vitro, a controlled, randomized study was
      designed to assess its effects on fatigued canine diaphragm in vivo, and compare
      these to the expected inotropic effects of aminophylline. Diaphragm fatigue was
      induced in 21 dogs using electrophrenic stimulation at 20 Hz until
      transdiaphragmatic pressure (Pdi) at 20 Hz was reduced to about 50% of its
      original value. After stabilization of fatigue, animals were randomized in three
      groups. Aminophylline-treated animals received an intravenous bolus of 20 mg/kg,
      broxaterol-treated animals were given an initial bolus of 100 micrograms/kg, and
      control animals obtained an equal load of saline. After 3 h, aminophylline
      treated animals and broxaterol-treated animals received a second dose of 20 mg/kg
      and 200 micrograms/kg, respectively, whereas control animals received a second
      dose of saline. Pdi was measured every 30 min for 6 h. At therapeutic serum
      levels, theophylline did not affect Pdi at any stimulation frequency compared
      with control conditions. In contrast, broxaterol administration resulted in a
      significant (p less than 0.05) and long-lasting increase in Pdi at low
      stimulation frequencies. Pdi at 20 Hz thus increased by 20 +/- 16% 90 min after
      the first bolus, and by 36 +/- 18% 90 min after the second dose. We conclude that
      (1) broxaterol promotes recovery of low-frequency fatigue in a dose-dependent
      way, and (2) theophylline does not improve the force output of fatigued canine
      diaphragm in vivo.

PMID- 1352667
TI  - Oxytocin in Maternal, Sexual, and Social Behaviors. Conference of the New York
      Academy of Sciences. Arlington, Virginia, May 19-22, 1991.

PMID- 1352665
TI  - Short-term interaction of airway and tissue oxygen tensions on ciliary beat
      frequency in dogs.
AB  - The responses of canine tracheal ciliary beat frequency (CBFt) to total lung,
      tracheal lumen, and peripheral lung hyperoxia, to tracheal lumen anoxia with or
      without peripheral lung hypoxia, and to isolated tracheal lumen hyperoxia
      combined with a beta-antagonist were delineated in anesthetized beagle dogs. CBFt
      was measured using a heterodyne laser light-scattering technique. When oxygen
      mixtures were delivered to the whole lung, a dose-dependent increase in maximal
      CBFt was observed from 6.3 +/- 1.0 Hz on air to 13.8 +/- 1.2 Hz on 100% oxygen.
      When oxygen mixtures were delivered to the isolated tracheal lumen, a dose
      dependent increase in maximal CBFt from 6.9 +/- 1.3 Hz on air to 25.7 +/- 6.3 Hz
      on 100% oxygen was observed. CBFt was unchanged under conditions of peripheral
      lung hyperoxia. There were no significant changes from room air baseline CBFt of
      7.6 +/- 1.5 Hz due to either isolated tracheal anoxia alone or in combination
      with alveolar hypoxia. CBFt stimulated with 100% oxygen insuffiated to the
      isolated tracheal lumen decreased from 14.1 +/- 3.2 to 9.5 +/- 1.9 Hz and from
      16.5 +/- 1.2 to 9.7 +/- 1.2 Hz in response to 6 and 18 micrograms/kg of
      intravenous esmolol, respectively. This study demonstrates that short-term, local
      hyperoxia stimulates CBFt and that a pulmonary or systemically derived factor can
      be activated to inhibit this stimulation. It indicates that acute airway anoxia
      and alveolar and blood hypoxia do not suppress ciliary beat frequency. It also
      suggests that the adrenergic system is involved in the oxygen-induced stimulation
      of ciliary beat.

PMID- 1352668
TI  - 1st Biennial Conference of the American Society of Tropical Veterinary Medicine.
      San Juan, Puerto Rico, February 5-8, 1991.

PMID- 1352669
TI  - Biotechnology: a new approach to the diagnosis and control of tick-borne
      hemoparasitic diseases.

PMID- 1352670
TI  - Frontiers in Cosmic Physics. Symposium in memory of Serge Alexander Korff. New
      York, New York, September 13, 1990.

PMID- 1352671
TI  - [High-dose chemotherapy with autologous stem cell transplantation--US-Japan
      Cooperative Cancer Research Program Seminar].

PMID- 1352672
TI  - A case of xeroderma pigmentosum group A diagnosed with a polymerase chain
      reaction (PCR) technique. Usefulness of PCR in the detection of point mutation in
      a patient with a hereditary disease.
AB  - BACKGROUND: The gene responsible for the xeroderma pigmentosum (XP) group A gene
      was recently identified and isolated. Preliminary study with fibroblasts from
      patients with XP group A revealed that most of the Japanese patients with XP
      group A have a point mutation at the 3' splice acceptor site of intron 3. This
      mutation site in the XP group A-complementing gene can be recognized by a
      restriction enzyme, AlwNI. This article describes the usefulness of the
      polymerase chain reaction diagnosis on XP group A. OBSERVATIONS: We tried a
      polymerase chain reaction diagnosis on genomic DNA from a sporadic case of XP
      group A and this child's parents. AlwNI restriction fragment length polymorphism
      of the polymerase chain reaction product showed three bands for his father's and
      mother's DNA, one corresponding to normal and two corresponding to a point
      mutated gene, respectively. A DNA sample from our patient showed two fragments
      indicating that only he has the mutated gene. CONCLUSIONS: This study
      demonstrated that we can know that this patient has group A XP without a
      complementation test that needs a lot of time. Moreover, our study revealed that
      we can detect the hidden mutated XP group A-complementing gene in the pedigree in
      which there is no patient with XP. Furthermore, it may be available soon for
      prenatal diagnosis.

PMID- 1352673
TI  - Late diagnosis of cryptorchidism: a failure of medical screening?
AB  - A retrospective review of hospital and available community records of 47 children
      undergoing orchidopexy in a district hospital was undertaken to determine
      adequacy of screening for cryptorchidism and factors associated with late
      referral. Twenty eight of these boys were previously examined on 108 occasions.
      Diagnosis was missed on 32 occasions and the record of 38 clinical examinations
      did not include position of testes. In the case of 16 boys (four under school age
      and 12 of school age) appropriate action was not taken once the diagnosis was
      made. Diagnosis was reliably made in school aged children but in children under
      the age of 1 year cryptorchidism was frequently missed by the examining doctor.
      It is suggested that criteria for diagnosis and referral should be agreed in any
      surveillance programme. Junior doctors in hospital responsible for routine
      clinical examination of children during admission and clinical medical officers
      or general practitioners during routine clinical examination of boys should be
      clearly instructed to examine and record the position of the testes.

PMID- 1352674
TI  - Does human T-cell lymphotropic virus type I and human immunodeficiency virus type
      1 coinfection accelerate acquired immunodeficiency syndrome? The jury is still
      out.

PMID- 1352675
TI  - The impact of human T-lymphotrophic virus type I/II infection on the prognosis of
      sexually acquired cases of acquired immunodeficiency syndrome.
AB  - Twenty (18%) of 111 Peruvian men with sexually acquired human immunodeficiency
      virus infection were found also to be infected with human T-lymphotrophic virus
      type I or II in a retrospective study. At the time of data evaluation, 75
      patients had reached Centers for Disease Control stage IV (clinical acquired
      immunodeficiency syndrome) and had not received antiviral medication; mortality
      in this group was 63.3% (38/60) among patients infected with human
      immunodeficiency virus alone and 80% (12/15) in the dually infected group. Of the
      50 patients who had died, survival time from onset of stage IV to death was
      shorter in the dually infected group (5.02 +/- 3.27 months) than in those with
      human immunodeficiency virus infection alone (10.07 +/- 4.42 months). In Peru,
      sexually acquired human immunodeficiency virus infection in men is often
      accompanied by human T-lymphotrophic virus type I/II infection, and dual
      retrovirus infection is associated with a shorter survival after onset of
      clinical acquired immunodeficiency syndrome.

PMID- 1352676
TI  - CD4 lymphocyte count as an indicator of delay in seeking human immunodeficiency
      virus-related treatment.
AB  - BACKGROUND: As many as half of patients infected with the human immunodeficiency
      virus who are medically eligible for Pneumocystis prophylaxis and zidovudine
      treatment have not received these treatments. We used the CD4 lymphocyte count as
      an indicator of delay in seeking treatment among patients infected with human
      immunodeficiency virus and assessed whether insurance status was associated with
      the stage of illness when care is initiated. METHODS: Data from 96 patients who
      initiated medical care at a university acquired immunodeficiency syndrome clinic
      from August 1989 to January 1991 were retrospectively reviewed. RESULTS: Patients
      initiated care at a relatively late stage of illness (mean CD4 lymphocyte count,
      0.37 x 10(9)/L [369/mm3]), and 29% were below the threshold for Pneumocystis
      prophylaxis. Patients with private insurance had significantly lower CD4 counts
      (mean, 0.27 x 10(9)/L) than did individuals with public insurance (mean, 0.46 x
      10(9)/L). CD4 counts did not increase during the 18-month study period.
      CONCLUSIONS: The majority of patients infected with human immunodeficiency virus
      are eligible for medical therapy and could benefit by initiating care sooner.
      Private insurance was not associated with initiating early care, supporting
      anecdotal reports that some privately insured individuals may be reluctant to
      seek care for a human immunodeficiency virus-related condition.

PMID- 1352678
TI  - In vivo occupancy of dopamine receptors by antipsychotic drugs.

PMID- 1352677
TI  - Positron emission tomographic analysis of central D1 and D2 dopamine receptor
      occupancy in patients treated with classical neuroleptics and clozapine. Relation
      to extrapyramidal side effects.
AB  - Positron emission tomography and selective radioligands were used to determine D1
      and D2 dopamine receptor occupancy induced by neuroleptics in the basal ganglia
      of drug-treated schizophrenic patients. In 22 patients treated with conventional
      dosages of classical neuroleptics, the D2 occupancy was 70% to 89%. Patients with
      acute extrapyramidal syndromes had a higher D2 occupancy than those without side
      effects. This finding indicates that neuroleptic-induced extrapyramidal syndromes
      are related to the degree of central D2 occupancy induced in the basal ganglia.
      In five patients treated with clozapine, the prototype atypical antipsychotic
      drug, a lower D2 occupancy of 38% to 63% was found. This finding demonstrates
      that clozapine is also "atypical" with respect to the central D2 occupancy in
      patients. During treatment with clozapine, there is a low frequency of
      extrapyramidal syndromes, which accordingly may reflect the comparatively low D2
      occupancy induced by clinical doses of clozapine. Classical neuroleptics, like
      haloperidol or sulpiride, did not cause any evident D1 occupancy, but the
      thioxanthene flupentixol induced a 36% to 44% occupancy. In four patients treated
      with clozapine, the D1 occupancy was 38% to 52%. The D1 occupancy induced by
      clozapine and flupentixol may contribute to the antipsychotic effect of these
      drugs.

PMID- 1352679
TI  - Functional expression of soluble ICAM-1 by baculovirus-infected Sf9 cells.
AB  - Inflammation, metastasis and ischemia are processes that require lymphocyte or
      leukocyte cell recognition and adherence to endothelial counter receptors such as
      ICAM-1. Mapping the sites of interaction of ICAM-1 with LFA-1, the receptor for
      ICAM-1 on lymphocytes, may lead to the design of novel inhibitors of inflammation
      or metastasis. To this end, recombinant soluble ICAM-1 cDNA was engineered into
      the baculovirus expression system, which is capable of expressing large amounts
      of proteins. These constructs were designed to contain a protein leader sequence
      so that the transfected insect cells would secrete the recombinant polypeptide
      into the culture media for ease of isolation. We engineered four constructs of
      ICAM-1 into the baculovirus system and obtained relatively high expression of two
      soluble forms of ICAM-1, a two domain and a five domain form. These truncated
      proteins were isolated and shown to promote adherence of HL-60 cells and Molt-4
      cells. These recombinant soluble proteins also inhibited cell adherence to
      purified intact ICAM-1 isolated from K562 cells.

PMID- 1352680
TI  - Interaction between phosphoinositide turnover system and cyclic AMP pathway for
      the secretion of pancreastatin and somatostatin from QGP-1N cells.
AB  - It is found that secretion of pancreastatin and somatostatin from QGP-1N cells is
      regulated through muscarinic receptor-mediated activation of
      phosphatidylinositide hydrolysis system. In this report, whether the cAMP pathway
      interacts with the phosphoinositide turnover system for the secretion of
      pancreastatin and somatostatin from QGP-1N cells through muscarinic receptors was
      studied. Stimulation of QGP-1N cells with carbachol increased intracellular cAMP
      levels. The carbachol-induced increase in cAMP levels was inhibited by atropine.
      Calcium ionophore (A23187) and phorbol 12-myristate 13-acetate increased cAMP
      synthesis. Dibutyryl cAMP, forskolin and theophylline stimulated secretion of
      pancreastatin and somatostatin. When either dibutyryl cAMP, forskolin or
      theophylline was added in culture medium with A23187, phorbol ester or carbachol,
      a synergistic effect was found on pancreastatin and somatostatin secretion. These
      results suggest that interaction between the phosphoinositide turnover system and
      the cAMP pathway occurs in QGP-1N cells through muscarinic receptor stimulation
      for the secretion of pancreastatin and somatostatin.

PMID- 1352681
TI  - Structures and properties of seven isoforms of the NMDA receptor generated by
      alternative splicing.
AB  - We here report the existence of 6 additional isoforms of the NMDA receptor
      generated via alternative splicing by molecular analysis of cDNA clones isolated
      from a rat forebrain cDNA library. These isoforms possess the structures with an
      insertion at the extracellular amino-terminal region or deletions at two
      different extracellular carboxyl-terminal regions, or those formed by
      combinations of the above insertion and deletions. One of the deletions results
      in the generation of a new carboxyl-terminal sequence. All these isoforms possess
      the ability to induce electrophysiological responses to NMDA and respond to
      various antagonists selective to the NMDA receptor in the Xenopus oocyte
      expression system. In addition, a truncated form of the NMDA receptor also exists
      that contains only the extreme amino-terminal sequence of this protein molecule.
      These data indicate that the NMDA receptor consists of heterogeneous molecules
      that differ in the extracellular sequence of the amino- and carboxyl-terminal
      regions.

PMID- 1352682
TI  - Nitroprusside-sensitive and insensitive guanylate cyclases in retinal rod outer
      segments.
AB  - Rod outer segments of retina contain guanylate cyclase activity both in the
      cytosol and membrane fractions. Though the activity in the cytosol is a small
      fraction of the total activity, it is highly activated by nitroprusside, a nitric
      oxide generating agent. The membrane guanylate cyclase on the other hand is
      unaffected by nitroprusside both before and after solubilization. The effects of
      nitroprusside or nitric oxide on photoreceptor function should therefore be
      mediated by the cytosolic and not the membrane guanylate cyclase.

PMID- 1352683
TI  - Inhibition of cellular glutathione biosynthesis by rifampicin in Mycobacterium
      smegmatis.
AB  - This study was carried out to investigate the mechanism of Rifampicin (RIF)
      induced glutathione (GSH) depletion in M. smegmatis. RIF at various
      concentrations decreased the activities of gamma glutamyl cysteine synthetase
      (GGCS) and GSH synthetase. Maximum decrease in the activities of biosynthetic
      enzymes of GSH was observed when 15 micrograms RIF ml-1 medium was incorporated
      in the growth medium before performing inoculations. The activity of GGCS was
      also decreased when three day grown M. smegmatis was exposed to 60 micrograms RIF
      ml-1 medium for a period of 6 h and 9 h. RIF did not alter the activity of gamma
      glutamyl transferase. The results of the present study demonstrate that the
      depletion caused by RIF in cellular GSH is due to its decreased biosynthesis
      whereas its degradation is not affected in M. smegmatis.

PMID- 1352684
TI  - Amyl nitrite: use as a smooth muscle relaxant in difficult preterm cesarean
      section.
AB  - Amyl nitrite is a smooth muscle relaxant that has been used clinically to
      facilitate uterine relaxation in difficult deliveries. In this retrospective
      study, we evaluate the safety of amyl nitrite use during preterm cesarean
      deliveries, and we assess possible advantageous effects on surgical incision
      choice. Women who received amyl nitrite cesarean section were compared to a
      control group matched for gestational age, fetal presentation, and mode of
      delivery who did not receive amyl nitrite. There were no statistical differences
      between the groups in the independent variables (maternal age, parity, medical or
      obstetric history, type of anesthesia, anesthesia or obstetric attending
      physician, antepartum hematocrit, or neonatal weight). Outcome (dependent)
      variables (estimated blood loss, Apgar scores, postpartum hematocrit, cord gases,
      or postpartum complications) were assessed, and there were no significant
      differences between the groups. Low transverse cesarean section was performed
      more frequently in the amyl nitrite group (58 of 64) than in the comparison group
      (48 of 64) (p less than 0.03). Considering the 128 women with and without amyl
      nitrite together, the decrease in hematocrit observed postpartum was greater
      after classic section (7%) than after low transverse section (4%) (p less than
      0.002). We conclude that the use of amyl nitrite during preterm cesarean section
      poses no threat to mother or fetus and may facilitate delivery by allowing the
      performance of a low transverse rather than a classic cesarean section without
      maternal or neonatal complications.

PMID- 1352685
TI  - C4 polymorphism in multiplex families with insulin dependent diabetes in the
      Tunisian population: standard C4 typing methods and RFLP analysis.
AB  - The polymorphism of C4A and C4B genes was investigated in Tunisian patients with
      insulin dependent diabetes (IDDM) and compared to family members (sibs) and to
      healthy controls. Multiplex families were analysed. A significant increase in
      C4AQO (26.86% vs 6.90%) and C4BQO (40.29% vs 8.28%) phenotypes was noted in IDDM
      patients compared with controls. Using RFLP analysis, we confirmed the high
      frequency of C4 null alleles. We also observed that most of these alleles were
      genes deleted in IDDM patients (72.23% vs 20% for CA4QO and 74.07% vs 16.70% for
      C4BQO). A significant decrease in the C4B long (14.92% vs 67.12%) form of the
      gene was also demonstrated by RFLP analysis compared with controls. Two
      haplotypes were frequently associated with IDDM patients in whom the C4A and C4B
      were deleted genes.

PMID- 1352686
TI  - Activation of CD4+ and CD8+ lymphocyte subsets by streptozotocin in murine
      popliteal lymph node (PLN) test.
AB  - Time-related and dose-related popliteal lymph node (PLN) enlargement and
      lymphocyte subset alterations owing to subcutaneous (s.c.) injection of
      streptozotocin (STZ) into the foot pad were determined in (C57BL/6 x DBA/2)F1
      [B6D2F1] mice. Early cell activation and time-related changes in T and B
      lymphocyte subsets were monitored during the onset of STZ-induced
      lymphoproliferative reaction by flow cytometry and immunophenotyping of
      lymphocyte subsets stained with a panel of monoclonal antibodies. Examination of
      cell size and chromatin decondensing for T and B cell subsets revealed
      differences in their activation profiles during the early phase of STZ-induced
      lymph node enlargement. The kinetics of the reaction showed initial activation
      and proliferation of CD4+ cells associated with accumulation of CD8+ and B cells.
      Subsequently CD8+ cells were activated and proliferated, but there was no
      evidence of early or late B cell activation as shown by the lack of increase in
      cell size or nuclear decondensation and the low and transient synthesis of
      immunoglobulins. The activation characteristics for CD4+ and CD8+ cell subsets in
      STZ-induced node enlargement were found to be analogous with T cell activation in
      acute allogeneic graft-versus-host (GVH) reaction in which the F1 recipient
      differed from the parent at both class I and II MHC loci. Our data support a
      central role for T cell activation in the induction of STZ-related PLN
      enlargement and suggest that recirculatory host B cells can play a major role in
      early node enlargement.

PMID- 1352687
TI  - Expression of c-erbB-2 in in situ and in adjacent invasive ductal adenocarcinomas
      of the female breast.
AB  - Several lines of evidence have demonstrated that expression of the c-erbB-2 gene
      product contributes to the malignant phenotype. We and others have determined
      that c-erbB-2 is substantially expressed in most ductal in situ carcinomas of the
      comedo type, but not in other patterns of ductal carcinoma in situ or in atypical
      ductal hyperplasia of the breast. In the present investigation, by
      immunohistochemistry we inquired whether invasive ductal adenocarcinomas retained
      the c-erbB-2 expression status of the in situ carcinomas from which they derived.
      Of twelve specimens containing both cribriform/micropapillary in situ and
      derivative invasive adenocarcinomas in the same section, all tumor cells were
      negative for c-erbB-2 expression. In thirteen in situ carcinomas of the comedo
      type, with identifiable invasive components, ten had definite c-erbB-2
      expression, and in every case there was comparable c-erbB-2 protein staining of
      in situ and invasive components; in three of these ten cases the staining in the
      in situ component tended to be more intense. These findings imply that a
      significant proportion of invasive mammary adenocarcinomas expressing c-erbB-2
      protein is derived from ductal in situ carcinomas of the comedo type.

PMID- 1352688
TI  - Detection of point mutations in p21ras genes.

PMID- 1352689
TI  - Detection of human retroviruses by PCR.

PMID- 1352690
TI  - Reactivity-based hydrocarbon controls: scientific issues and potential regulatory
      applications.
AB  - The California Air Resources Board and the South Coast Air Quality Management
      District hosted a conference on April 8-9, 1991 to examine the scientific issues
      associated with reactivity-based hydrocarbon controls, and to identify the
      obstacles to potential regulatory applications. Owing to residual uncertainties
      in the underlying science, and the complex emission measurement capabilities
      required for enforcement, a general consensus emerged on the need for further
      research before application of reactivity-based controls. A number of
      recommendations were made for research on the remaining scientific, enforcement,
      and policy issues, many of which have led to cooperative efforts initiated since
      the conference.

PMID- 1352691
TI  - Hox genes: a role for tissue development.

PMID- 1352692
TI  - Regulation of type I and type II transglutaminase in normal human bronchial
      epithelial and lung carcinoma cells.
AB  - In cultured, undifferentiated normal human bronchial epithelial (HBE) cells,
      transglutaminase activity was localized predominantly in the cytosolic fraction
      of cell lysates. Upon squamous differentiation, this cytosolic activity declined
      and was replaced by a 40-fold increase in the activity of particulate (membrane
      associated) transglutaminase. Immunoblot analysis demonstrated that the cytosolic
      transglutaminase was Type II (tissue) transglutaminase and that squamous
      differentiation shifted gene expression to the Type I (epidermal)
      transglutaminase. Retinoic acid, an inhibitor of squamous cell differentiation,
      suppressed the increase in Type I transglutaminase. The decrease in Type II
      transglutaminase activity was unaffected by retinoic acid. Transforming growth
      factor-beta 1 (TGF-beta 1) enhanced Type II transglutaminase activity about 10
      fold in the undifferentiated cells but did not increase Type I transglutaminase
      or cholesterol sulfate, two early markers of squamous differentiation. TGF-beta 2
      was equivalent to TGF-beta 1 in inducing Type II transglutaminase and in
      inhibiting the growth of HBE cells. The differentiation-related and TGF-beta
      induced changes in transglutaminase activity were reflected in the level of
      transglutaminase Type I and Type II protein and mRNA. Expression of
      transglutaminases in lung carcinoma cell lines was variable. No correlation was
      observed between the expression of Type I transglutaminase and the classification
      of the cells as squamous cell carcinoma. Several lung carcinoma cell lines
      exhibited high levels of Type II transglutaminase activity that were increased
      several-fold by TGF-beta 1 treatment. Retinoic acid was ineffective in altering
      transglutaminase expression in most cell lines but induced Type II
      transglutaminase in a time- and dose-dependent manner in NCI-HUT-460
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352693
TI  - [XIII Portuguese Congress of Cardiology. Abstracts].

PMID- 1352694
TI  - Detection of mutations in human DNA.
AB  - Efficient methods for the detection of mutations are of fundamental importance in
      research and in diagnostics. By detection of a DNA sequence alteration that
      cosegregates with a clinical phenotype in an affected family, the gene at fault
      may be identified and assigned a function. Mutation detection methods are also a
      rate-limiting factor for the clinical application of DNA diagnostics. Currently a
      large number of techniques are in use to scan for new mutations and to
      distinguish among previously established sequence variants. Here, some of the
      problems connected with mutation detection are discussed together with principles
      on which current and future mutation detection assays can be based.

PMID- 1352695
TI  - Optimized centrifugation for rapid elution of DNA from agarose gels.
AB  - A simple method has been developed for the isolation of DNA from agarose gels.
      Centrifugation in a low-cost device for 45 s at low speed provides a high yield
      of DNA suitable for further manipulation by restriction enzymes, T4 DNA ligase,
      Taq polymerase, Klenow fragment, and T4 polynucleotide kinase, and also for
      sequencing. In contrast, centrifugation for greater than 1 min leads to coelution
      of substances that inhibit DNA ligase.

PMID- 1352696
TI  - Mechanism of multidrug resistance in human tumour cell lines and complete
      reversion of cellular resistance.
AB  - The biochemical basis of the multidrug-resistant (MDR) phenotype has been
      investigated in drug-resistant sublines derived from LoVo and SW984 human colon
      carcinoma cell lines by doxorubicin selection. Besides drug extrusion through the
      plasma membrane, two further observations, both ascribable to the drug transport
      property of the gp170 glycoprotein, were made. First drug deposition into
      cytoplasmic membranous structures which allows cells to tolerate a high
      intracellular drug concentration since it prevents drugs from reaching their
      cellular target site(s). Secondly drug removal from the complexes formed by
      interaction of drug with target cellular macromolecules, a phenomenon which
      extends its an effect that continues after treatment and appears to be the most
      important resistance mechanism in MDR cells. Treatments based on the gp170
      inhibitory property of verapamil were developed that allowed abrogation of
      resistance in MDR cell lines, a strategy that may be applicable to therapy
      treatments.

PMID- 1352697
TI  - Caring for the cancer patient: managing emesis now. An interactive workshop.
      Proceedings of a satellite symposium to the 6th European Conference on Clinical
      Oncology. Florence, October 1991.

PMID- 1352698
TI  - Segmental determination in Drosophila central nervous system: analysis of the
      abdominal-A region of the bithorax complex.
AB  - The bithorax complex (BX-C) comprises several genes required for the
      diversification of posterior segments in Drosophila. The BX-C genes control
      segment differences not only in the epidermis but in other tissues as well,
      especially in the central nervous system. We have examined the control of one
      segment-specific neural structure: the lateral dots, a paired structure present
      in the first abdominal segment of the larval CNS and absent in all following
      abdominal segments. Our results show that the suppression of lateral dots in
      segments A3 and A4 requires the presence of two active copies of one of the BX-C
      genes, abdominal-A (abd-A). We also show that the adjacent BX-C regions, iab-3
      and iab-4, can act in trans on abd-A not only when the two copies of BX-C are
      paired but also, at least to some extent, when pairing is disturbed.

PMID- 1352699
TI  - Ancestral haplotypes carry haplotypic and haplospecific polymorphisms of BAT1:
      possible relevance to autoimmune disease.
AB  - The human BAT1 gene, located in the central MHC region (approximately 170 kb
      centrometric of HLA-B), is polymorphic and the polymorphism correlates with MHC
      ancestral haplotypes. Allelic RFLP patterns have been assigned to several
      ancestral haplotypes and have been shown to be 'haplotypic' (i.e. found on all
      examples of the same ancestral haplotype) and in some cases 'haplospecific' (i.e.
      unique to one ancestral haplotype). The relevance of the BAT1 polymorphism to
      susceptibility to Myasthenia Gravis (MG) has been investigated. The frequency of
      the BAT1 B allelic pattern is increased in patients with MG (n = 16) compared to
      an equal number of control subjects. The increase is due to the association
      between MG and the 8.1 ancestral haplotype (HLA A1, Cw7, B8, BfS, C4AQ0, C4B1,
      DR3, DQw2).

PMID- 1352700
TI  - Polymorphism in the human B144 gene in different MHC haplotypes.

PMID- 1352701
TI  - Non-radioactive ASO typing for class II--the way forward.

PMID- 1352702
TI  - Functional analysis of chimeric proteins constructed by exchanging homologous
      domains of two P-glycoproteins conferring distinct drug resistance profiles.
AB  - P-Glycoproteins (P-gps) encoded by the mouse mdr1 and mdr3 (Phe939, mdr3F) genes
      confer distinct drug resistance profiles. While the mdr1 and mdr3F clones confer
      comparable levels of vinblastine (VBL) resistance, mdr3F confers actinomycin D
      (ACT) resistance levels 2-fold greater than mdr1, while mdr1 confers resistance
      to colchicine at levels 7-fold greater than mdr3F. We wished to identify in
      chimeric proteins discrete protein domains responsible for the distinct drug
      resistance profiles of mdr1 and mdr3F. Homologous protein domains were exchanged
      in hybrid cDNA clones, and the specific drug resistance profiles conferred by
      chimeric proteins were determined in stably transfected cell clones expressing
      comparable amounts of wild-type or chimeric P-gps. Immunoblotting experiments
      showed that all chimeras were found expressed in membrane-enriched fractions of
      transfected cell clones and all conveyed cellular drug resistance at levels above
      the background of nontransfected drug-sensitive LR73 cells. For VBL, all chimeric
      constructs were found to convey similar levels of resistance. For COL and ACT,
      the levels of resistance conferred by the various chimeras were heterogeneous,
      being similar to either the parental mdr1 or the parental mdr3F clones, or in
      many cases being intermediate between the two. The preferential COL and ACT
      resistance phenotypes of mdr1 and mdr3F, respectively, did not segregate in
      chimeric proteins with any specific protein segment. Taken together, our results
      suggest that the preferential drug resistance phenotypes encoded by the mdr1 and
      mdr3F clones implicate complex interactions between the two homologous halves of
      the respective P-gp.

PMID- 1352703
TI  - The effects of a dopamine antagonist on luteinizing hormone and prolactin release
      in women with anorexia nervosa and in normal controls.
AB  - To evaluate the possible role of central dopaminergic suppression of gonadotropin
      secretion in the genesis of amenorrhea associated with anorexia nervosa (A.N.), a
      central D-2 dopamine receptor blocker was administered to 10 women with A.N. and
      10 regularly menstruating age-matched controls. Serum prolactin and luteinizing
      hormone (LH) levels were measured at -15, 0, 30, 60, 120, and 180 min after
      administration of metoclopramide (10 mg orally). Mean basal prolactin (p less
      than 0.001) and estradiol levels (p less than 0.02) were significantly lower in
      women with A.N. The prolactin response to metoclopramide was significantly
      impaired in women with anorexia nervosa. No correlation was found between the
      prolactin response and percentage ideal body weight. Basal and post-stimulation
      prolactin levels were correlated with estradiol levels. After adjusting for the
      effects of estradiol, significant differences between patients with A.N. and
      controls remained in prolactin levels at baseline (p less than 0.01), 120 min (p
      less than 0.02) and 180 min (p less than 0.05). Metoclopramide did not induce a
      significant rise in LH levels in either the A.N. or control groups. These data
      are consistent with central dopaminergic inhibition of prolactin secretion in
      anorexia nervosa but do not support the hypothesis that central dopaminergic
      inhibition is related to diminished LH release in this state.

PMID- 1352704
TI  - Molecular cloning and sequence analysis of human dipeptidyl peptidase IV, a
      serine proteinase on the cell surface.
AB  - The cDNA coding for the human dipeptidyl peptidase IV (DPPIV) has been isolated
      and sequenced. The nucleotide sequence (3465 bp) of the cDNA contains an open
      reading frame encoding a polypeptide comprising 766 amino acids, one residue less
      than those of rat DPPIV. The predicted amino acid sequence exhibits 84.9%
      identity to that of the rat enzyme, and contains nine potential N-linked
      glycosylation sites, one site more than those in the rat enzyme. A putative
      catalytic triad for serine proteinases, serine, aspartic acid and histidine, are
      found in a completely conserved COOH-terminal region (positions 625-752).

PMID- 1352705
TI  - P-glycoprotein as multidrug transporter: a critical review of current multidrug
      resistant cell lines.
AB  - MDR has been studied extensively in mammalian cell lines. According to usual
      practice, the MDR phenotype is characterized by the following features: cross
      resistance to multiple chemotherapeutic agents (lipophilic cations), defective
      intracellular drug accumulation and retention, overexpression of P-gp (often
      accompanied by gene amplification), and reversal of the phenotype by addition of
      calcium channel blockers. An hypothesis for the function of P-gp has been
      proposed in which P-gp acts as a carrier protein that actively extrudes MDR
      compounds out of the cells. However, basic questions, such as what defines the
      specificity of the pump and how is energy for active efflux transduced, remain to
      be answered. Furthermore, assuming that P-gp acts as a drug transporter, one will
      expect a relationship between P-gp expression and accumulation defects in MDR
      cell lines. A review of papers reporting 97 cell lines selected for resistance to
      the classical MDR compounds has revealed that a connection exists in most of the
      reported cell lines. However, several exceptions can be pointed out. Furthermore,
      only a limited number of well characterized series of sublines with different
      degrees of resistance to a single agent have been reported. In many of these, a
      correlation between P-gp expression and transport properties can not be
      established. Co-amplification of genes adjacent to the mdr1 gene, mutations
      [122], splicing of mdr1 RNA [123], modulation of P-gp by phosphorylation [124] or
      glycosylation [127], or experimental conditions [26,78] could account for some of
      the complexity of the phenotype and the absence of correlation in some of the
      cell lines. However, both cell lines with overexpression of P-gp without
      increased efflux [i.e., 67,75] and cell lines without P-gp expression and
      accumulation defects/increased efflux [i.e., 25,107] have been reported. Thus,
      current results from MDR cell lines contradict--but do not exclude--that P-gp
      acts as multidrug transporter. Other models for the mechanism of resistance have
      been proposed: (1) An energy-dependent permeability barrier working with greater
      efficacy in resistant cells. This hypothesis is supported by studies of influx
      which, although few, all except one demonstrate decreased influx in resistant
      cells; (2) Resistant cells have a greater endosomal volume, and a greater
      exocytotic activity accounts for the efflux.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1352706
TI  - Effects of free and liposome-encapsulated taxol on two brain tumors xenografted
      into nude mice.
AB  - Free taxol and liposome-encapsulated taxol were compared for their antitumoral
      activities on two human brain tumors serially grafted into female athymic mice in
      the scapular region. In the first experiment, a human glioblastoma (15th and 16th
      passages) was studied. In the second experiment, a fast growing human gliosarcoma
      (19th passage) was used. Free taxol and liposomal taxol were administered
      intraperitoneally, at the same dose; 12.5 mg/kg (i.e. 1/15 of the evaluated LD 50
      value). In the first experiment, the treatment was performed for four consecutive
      days, with four courses separated by three rest periods of three days in between.
      Both free taxol and encapsulated taxol produced a statistically significant delay
      in tumor growth, and at the end of the experiment some total tumor regressions
      were obtained. However, liposomes were observed to be more effective in their
      action on the two consecutive passages of the glioblastoma, giving a marked
      increase of the number of total tumor regressions. In the second experiment
      another schedule of treatment was chosen because of the fast growth pattern of
      the xenografted human gliosarcoma: free taxol and liposome-encapsulated taxol
      were administered for five consecutive days and three courses of treatment were
      performed with two rest periods of two days. The two forms of taxol had a
      significant inhibitory effect on gliosarcoma tumor growth; as before
      encapsulation in liposomes was found to increase the anti-tumoral activity of
      taxol, although, in this case no tumor regression was observed.

PMID- 1352707
TI  - Evidence that endogenous somatostatin (SRIF) exerts a tonic inhibitory effect on
      the rat renin--angiotensin--aldosterone system.
AB  - The bolus ip. administration of a SRIF antagonist (SRIF-A) (60 nM/rat)
      significantly increased renin activity (PRA) and plasma aldosterone concentration
      (PAC) in rats, without affecting natremia, kalaemia and the blood levels of ACTH
      or corticosterone. SRIF-A also raised PAC in rats whose renin-angiotensin system
      had been pharmacologically interrupted by combined captopril/angiotensin-II
      infusion and in which PRA was very low. The ip. injection of an equimolar dose of
      SRIF completely reversed these effects of SRIF-A, but the administration of SRIF
      alone did not affect either PRA or PAC. Taken together, these data would suggest
      that, in the rat, endogenous SRIF exerts, under basal conditions, a two-fold
      maximum tonic inhibitory effect on both renin release by kidneys and aldosterone
      secretion by zona glomerulosa cells.

PMID- 1352708
TI  - Protein folding and chaperonins.
AB  - The folding of polypeptide chains in cells, following either translation or
      translocation through membranes, must take place under conditions of extremely
      high protein concentrations. In addition, folding into a correct structure must
      occur in the presence of other rapidly folding species, and at temperatures known
      to destabilize aggregation-prone folding intermediates. To facilitate folding in
      vivo, molecular chaperones have evolved that stabilize protein folding
      intermediates, thus partitioning them towards a pathway leading to the native
      state rather than forming inactive aggregated structures.

PMID- 1352709
TI  - Intrathymic activation events and the generation of IL-4 producer CD4+8-
      thymocytes.
AB  - The generation of mouse CD4+8- thymocytes appears to involve an activation
      process. CD69, an early activation marker, is first expressed on 3% of TCRlo/med
      double-positive thymocytes and peaks (70-90%) at the HSAhi TCRmed CD4+8lo and the
      HSAhi TCRhi CD4+8- stages, before being downmodulated. CD44, a marker of a later
      stage of activation is selectively expressed at the HSAlo CD4+8- stage.
      Functional changes associated with the late activated state, such as the
      transient acquisition of the potential to secrete IL-4 upon stimulation, are also
      induced at the HSAlo CD4+8- stage and are still evident after export to the
      periphery. During thymic selection, interactions of different affinities between
      TCR/CD4 and self ligand/MHC class II, are likely to induce different degrees of
      activation. This may impart different functional capabilities--such as the
      potential to secrete IL-4--to a subset of emerging CD4+ T lymphocytes that
      express TCRs with intermediate affinities for self. Such a pathway may be
      involved in the maintenance of tolerance and the prevention of some deleterious
      autoimmune reactions.

PMID- 1352710
TI  - Induction of CD11a/leukocyte function antigen-1 and CD54/intercellular adhesion
      molecule-1 on hairy cell leukemia cells is accompanied by enhanced susceptibility
      to T-cell but not lymphokine-activated killer-cell cytotoxicity.
AB  - Some B-cell neoplasms, including hairy cell leukemia (HCL), lack expression of
      the adhesion molecule leukocyte function antigen-1 (LFA-1/CD11a). Additionally,
      HCL cells express relatively low amounts of intercellular adhesion molecule-1
      (ICAM-1/CD54) and may therefore be an inappropriate target for recognition by T
      cells or lymphokine-activated killer (LAK) cells. We tested whether these
      molecules were inducible on HCL cells and if induction would lead to enhanced
      susceptibility to lysis by LAK cells or cytolytic T cells. CD11a expression was
      induced by incubation with interferon-alpha (IFN-alpha) or interleukin-4. CD54
      was induced by culturing the cells irrespectively of the addition of cytokines.
      Expression of CD11a and CD54 did not enhance susceptibility to either autologous
      or allogeneous LAK cells. However, induction of these adhesion molecules was
      accompanied by enhanced susceptibility to lysis by cytotoxic T lymphocyte clones.
      This lysis could be reversed by the addition of anti-CD11a and anti-CD54
      antibodies. Finally, we monitored the expression of CD11a and CD54 on HCL cells
      from patients during IFN-alpha therapy. In one of four patients monitored, we
      observed rapid in vivo induction of CD11a and CD54 on the leukemic cells during
      IFN-alpha therapy. These studies provide a model for studying immunosurveillance
      in HCL.

PMID- 1352711
TI  - A homologue of the Drosophila female sterile homeotic (fsh) gene in the class II
      region of the human MHC.
AB  - The RING3 gene maps in the class II region of the human major histocompatibility
      complex, at a CpG island distal of the HLA-DNA gene. RING3 cDNAs were obtained
      from a T cell cDNA library and the longest (4 kb) was sequenced. The sequence
      contained an open reading frame encoding a protein of 754 amino acids. A screen
      of protein databases revealed striking homology between the RING3 protein and the
      Drosophila female sterile homeotic gene (fsh) which is implicated in the
      establishment of segments in the early embryo. Partial sequence homology was also
      observed with some other proteins involved in cell cycle control (CCG1), cell
      division (ftsA) and regulation of cell growth (gamma interferons). This highly
      conserved gene may play an important role in human development. In addition, its
      location in the MHC class II region may be related to some HLA-associated
      diseases.

PMID- 1352712
TI  - The complete nucleotide sequence of region 1 of the CFA/I fimbrial operon of
      human enterotoxigenic Escherichia coli.
AB  - The production of the plasmid-encoded fimbrial antigen CFA/I of enterotoxigenic
      Escherichia coli requires two DNA regions: CFA/I region 1 and CFA/I region 2.
      These two regions are separated by about 40 kb on the wildtype plasmid. CFA/I
      region 1 contains the structural genes, whereas CFA/I region 2 contains a
      positive regulator. The first two genes (cfaA and cfaB) and the cfaD' sequence of
      region 1 have already been described. Here the total nucleotide sequence of
      region 1 is presented. Two new genes in region 1 are described, named cfaC and
      cfaE. The GC content of the genes in region 1 is 33.6% which is substantially
      lower than normally found in E. coli genes (50%). The codon usage also differs
      from the standard codons used in E. coli.

PMID- 1352713
TI  - What's new in neonatal nursing care? 1st International Neonatal Nursing
      Conference.

PMID- 1352714
TI  - A longitudinal study of correlations among tardive dyskinesia, drug-induced
      parkinsonism, and psychosis.
AB  - Tardive dyskinesia (TD) and drug-induced parkinsonism (DIP) have been
      hypothesized to reflect opposing states of dopamine (DA) function. In this
      longitudinal study, 57 psychotic inpatients were rated repeatedly for TD, DIP,
      and psychosis while receiving neuroleptic medication. Cross-sectional
      correlations among TD, DIP, and psychosis were weak or nonexistent. Factor and
      cluster analyses found that 13 patients (23%) were classified into groups
      characterized by the expected negative correlations. Thus, only partial support
      was found for the hypothesis that TD and DIP represent opposing states of DA
      function.

PMID- 1352715
TI  - MRC trial of treating hypertension in older adults.

PMID- 1352716
TI  - MRC trial of treating hypertension in older adults.

PMID- 1352717
TI  - Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)
      subsequent to chemotherapy improves collection of blood stem cells for
      autografting in patients not eligible for bone marrow harvest.
AB  - Fourteen patients with relapsed Hodgkin's disease responded to a salvage therapy
      with Dexa-BEAM (dexamethasone, BCNU, etoposide, Ara-C and melphalan). In seven
      patients a continuous i.v. infusion with recombinant human granulocyte-macrophage
      colony-stimulating factor (rhGM-CSF) was started subsequent to Dexa-BEAM (+rhGM
      CSF) while the other seven patients received no hemopoietic growth factor (-rhGM
      CSF). It was our objective to study the impact of rhGM-CSF on the collection of
      blood-derived hemopoietic stem cells in patients with extensive prior chemo- and
      radiotherapy not eligible for marrow harvest. Compared to baseline, we observed a
      significant increase of colony-forming units granulocyte-macrophage (CFU-GM) in
      the peripheral blood of patients receiving rhGM-CSF (p less than 0.05). On
      average, the yield of total nucleated cells and CFU-GM collected per single
      leukapheresis was 2.2 and 2.4-fold higher in the rhGM-CSF-treated patients
      respectively (p less than 0.05). With rhGM-CSF the interval from the start of
      chemotherapy to the end of blood stem cell collection could be reduced by 6 days
      (p less than 0.05). Following the CBV pretransplant regimen (cyclophosphamide,
      BCNU, etoposide), the reinfusion of rhGM-CSF-exposed stem cells resulted in a
      shorter time of leukocyte recovery (p less than 0.05). The number of CFU-GM/kg
      body weight transplanted was found to be predictive for the time of neutrophil
      recovery (p less than 0.05). In patients with bone marrow hypoplasia or fibrosis,
      rhGM-CSF as part of an effective salvage therapy improves the collection of blood
      stem cells that are capable of restoring hemopoiesis after high-dose
      pretransplant therapy.

PMID- 1352718
TI  - Sympathoinhibitory effects of rilmenidine may be mediated by sites located below
      the brainstem.
AB  - 1. To determine the site of action of rilmenidine, we examined its effets on
      arterial blood pressure (BP), heart rate (HR) and postganglionic renal
      sympathetic nerve activity (RSNA) after intracerebroventricular (i.c.v.)
      administration (300 micrograms kg-1), in groups (all n = 6) of conscious and
      freely moving, pentobarbitone-anaesthetized and pentobarbitone-anaesthetized and
      spinally transected, fifteen week-old male spontaneously hypertensive rats
      (SHRs). 2. In conscious SHRs, which exhibited a low sympathetic nerve activity
      (RSNA: 3.4 +/- 0.9 muV), rilmenidine was inactive on systolic BP (SBP), diastolic
      BP (DBP), HR and RSNA. 3. In intact pentobarbitone-anaesthetized SHRs, which
      exhibited an elevated sympathetic nerve activity (RSNA: 10.6 +/- 0.9 muV),
      rilmenidine exerted potent antihypertensive (delta SBP: -37 +/- 4%; delta DBP: 
      43 +/- 6%), bradycardic (delta HR: -32 +/- 3%) and sympathoinhibitory (delta
      RSNA: -68 +/- 9%) activities. 4. In pentobarbitone-anaesthetized SHRs with
      cervical spinal cord transection, BP was markedly decreased and sympathetic nerve
      activity (RSNA: 10.3 +/- 3.1 muV) returned to the level observed in conscious
      SHRs (RSNA: 3.6 +/- 0.5 muV). In these conditions, rilmenidine remained
      sympathoinhibitory (delta RSNA: -74 +/- 5%). 5. In conclusion, we have shown that
      pentobarbitone-anaesthesia enhances the peripheral sympathetic tone by a central
      action, as the spinal cord transection allows RSNA to return to normal levels and
      that, spinal or ganglionic structures could be a major site of the
      sympathoinhibitory action of rilmenidine.

PMID- 1352719
TI  - Influence of anaesthesia on the cardiovascular effects of rilmenidine and
      clonidine in spontaneously hypertensive rats.
AB  - 1. The acute cardiovascular effects of two alpha 2-adrenoceptor agonists,
      rilmenidine and clonidine, were studied in 15-week-old male spontaneously
      hypertensive rats (SHRs). The effects of these drugs were compared with
      intravenous (i.v.) and intracerebroventricular (i.c.v.) administration in
      conscious and pentobarbitone-anaesthetized SHRs, in which aortic blood pressure
      (BP) was continuously recorded. 2. In conscious SHRs, i.v. doses of either
      rilmenidine (30, 100, 300 micrograms kg-1) or clonidine (3, 10, 30 micrograms kg
      1) induced dose-dependent short-lasting increases in BP followed by moderate
      decreases associated with bradycardia, while the same three doses of both drugs
      given i.c.v. were devoid of BP and heart rate (HR) effects. 3. Pentobarbitone
      anaesthesia increased the sympathetic control of BP and suppressed the cardiac
      baroreflex sensitivity. 4. In anaesthetized SHRs, i.v. injections of the same 3
      doses of rilmenidine and clonidine induced a slight increase in BP, rapidly
      followed by profound and long-lasting BP and HR decreases. Surprisingly, when
      given i.c.v., these 3 doses lowered BP and HR to the same extent but in a more
      progressive manner. 5. The lack of efficacy of both drugs in conscious SHRs after
      the i.c.v. administration of i.v. active doses and the lack of more marked and
      rapid effects in anaesthetized SHRs, after i.c.v. than after i.v. injections,
      question the involvement of a major central site of action for these
      antihypertensive alpha 2-adrenoceptor agonists. Moreover, these results show that
      the cardiovascular effects of these drugs are profoundly influenced by baseline
      sympathetic nervous system activity which is enhanced by pentobarbitone
      anaesthesia.

PMID- 1352720
TI  - Characterization of histamine-H3 receptors controlling non-adrenergic non
      cholinergic contractions of the guinea-pig isolated ileum.
AB  - 1. In the presence of atropine, mepyramine and ranitidine, electric field
      stimulation of the guinea-pig isolated ileum longitudinal muscle-myenteric plexus
      preparation resulted in a two component non-adrenergic non-cholinergic
      contraction. The initial contraction had a duration of approximately 1 s whereas
      the second contraction lasted approximately 10 s. The second contraction was
      completely inhibited by tetrodotoxin (0.2 x 10(-6) M) with minimal effect on the
      initial contraction. Phentolamine (3 x 10(-6) M), propranolol (3 x 10(-6) M) and
      hexamethonium (10(-4) M), did not significantly reduce either component of the
      contractile response. 2. The neurokinin NK1 receptor antagonists, GR82334 and
      GR71251, produced concentration-related (EC50 = 564 and 173 nM respectively)
      inhibitions of the second contraction with no effect on the initial contraction.
      The neurokinin NK2 receptor antagonists MEN 10207 and Ac-Leu-Asp-Gln-Trp-Phe-Gly
      NH2 (R 396), 1 x 10(-9)-10(-5) M, were without effect on either component of the
      contractile response. 3. Concentration-related inhibitions of the second
      contraction, with no effect on the initial contraction, were observed after
      inclusion of the histamine H3 receptor agonists (R)-alpha-methylhistamine (pD2 =
      7.6), N alpha-methylhistamine (pD2 = 7.7) and N alpha,N alpha-dimethylhistamine
      (pD2 = 6.3). Histamine also inhibited the second contraction (pD2 = 6.2) in a
      concentration-related manner but produced a lower maximum inhibitory effect than
      the other agonists tested. 4. Inclusion of the H3 receptor antagonists,
      thioperamide, burimamide, impromidine and phenylbutanoylhistamine, caused
      parallel concentration-related rightward shifts in the concentration-response
      curve to (R)-alpha-methylhistamine. In each case, Schild analysis of these data
      gave slopes not significantly different from unity. Antagonist affinity values
      for thioperamide (pA2 = 8.2), burimamide (pA2 = 7.0) and impromidine (pA2 = 7.0)
      were consistent with values obtained in other assays of the H3 receptor. However,
      phenylbutanoylhistamine (pA2 = 5.8) and betahistine (pKB < 4) had affinities more
      than ten fold lower than values obtained in other assays of the H3 receptor.5.
      Exposure of the tissues to N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (10-6
      M) for 7-30min followed by extensive washing, had no effect on basal
      contractions, but produced a rightward shift in the concentration-response curves
      to (R-alpha-methylhistamine, Nalpha"-methylhistamine, Nalpha",Nalpha
      dimethylhistamine and histamine. This treatment also resulted in a decrease in
      the maximum inhibitory response obtainable. Apparent agonist affinity (pKD)
      values of 7.01, 7.06, 6.09 and 6.13 were estimated for (R)-alpha-methylhistamine,
      Nalpha-methylhistamine, Nalpha',Nalpha"-dimethylhistamine and histamine
      respectively.6. In conclusion, pharmacological analysis has revealed that
      histamine H3 receptors in the guinea-pig ileum modulate the release of non
      adrenergic non-cholinergic neurotransmitters, one of which is probably substance
      P. In addition we have identified N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline
      as an irreversible antagonist at H3 receptors and have used this compound to
      estimate apparent affinity values of agonists at H3 receptors in this
      preparation.

PMID- 1352721
TI  - Release of vasoactive intestinal polypeptide from the rat gastric fundus.
AB  - 1. Auxotonic responses and release of vasoactive intestinal polypeptide-like
      immunoreactivity (VIP-LI) induced by electrical field stimulation (EFS) were
      studied in longitudinal muscle strips from the gastric fundus of reserpinized
      rats suspended between parallel platinum electrodes in Krebs solution containing
      atropine (1 microM), 5-hydroxytryptamine (3 microM) and bovine serum albumin (50
      mg l-1). 2. EFS (supramaximal voltage, 1 ms, 0.25-32.0 Hz, trains of 2 min)
      induced frequency-dependent relaxations. 3. EFS at frequencies greater than or
      equal to 8 Hz also produced significant increases in VIP-LI release. 4. VIP-LI
      release induced by EFS at 16 Hz no longer occurred in the presence of
      tetrodotoxin (1 microM) or a Ca(2+)-free medium. 5. Detection of VIP-LI upon
      activation of inhibitory non-adrenergic, non-cholinergic neurones indicates that
      VIP meets the 'detectable release' criterion for an inhibitory neurotransmitter
      in the rat gastric fundus.

PMID- 1352722
TI  - The effect of adrenoceptor antagonists on the ileal brake mechanism in the rat.
AB  - 1. Studies were carried out in the rat to investigate the effect of adrenoceptor
      antagonists on stomach to caecum transit time under control conditions and during
      ileal infusion of Intralipid. Stomach to caecum transit time (SCTT) of the head
      of the meal was measured by use of environmental hydrogen analysis and the
      distribution of the meal was assessed by a scintigraphic technique. 2. Four
      adrenoceptor antagonists were used in these studies, the alpha 1 antagonist
      prazosin, the alpha 2 antagonist, idazoxan, the beta 1 antagonist atenolol and
      the beta 2 antagonist ICI 118551. 3. None of the antagonists affected SCTT of the
      head of the meal during ileal infusion of saline. However, the alpha 1 and beta 1
      antagonists significantly reversed (P less than 0.05) the delay in SCTT induced
      by ileal infusion of Intralipid whereas the alpha 2 antagonist, idazoxan,
      potentiated this delay (P less than 0.05). 4. Study of the distribution of the
      radiolabelled meal showed that the Intralipid delayed SCTT by slowing both
      gastric emptying (P less than 0.05) and small bowel transit (P less than 0.05).
      5. Prazosin delayed gastric emptying under control conditions (P less than 0.001)
      but did not alter significantly the effect of ileal lipid on the distribution of
      the meal, 100 min or 200 min after gavage.6. The meal distribution was more
      compatible with the hydrogen analysis after administration of the ,beta
      adrenoceptor antagonists. The reversal of the lipid-induced delay in SCTT caused
      by atenolol was associated with more radioactivity in the large intestine 200min
      after the gavage. ICI 118551 had no significant effects on either the
      distribution of the meal or the SCTT of the head of the meal.7. In conclusion,
      the data confirm that the sympathetic nervous system normally modulates or
      mediates the mechanisms that influence gastrointestinal transit in the rat and
      suggest that these mechanisms may be involved in the ileal brake effect.
      Nevertheless the data also suggest that simple measurement of the transit of the
      head of the meal by use of environmental hydrogen analysis may sometimes give a
      misleading impression of the action of drugs on gastrointestinal transit of the
      bulk of a test meal.

PMID- 1352723
TI  - Variations among rheumatologists in prescribing and monitoring of disease
      modifying antirheumatoid drugs.
AB  - One hundred consultant rheumatologists were sent a questionnaire on their
      prescribing pattern, and dose and monitoring schedules of four disease modifying
      antirheumatoid drugs (DMARDs). Seventy-five completed questionnaires were
      received. Sulphasalazine was the most popular first choice DMARD. There was
      general agreement on dose schedules which were similar to those recommended in
      the data sheets although for each drug a minority used different dose schedules.
      There was, however, marked variation among respondents in what was accepted as an
      adequate trial of therapy, in monitoring schedules and in the interpretation of
      results of toxicity monitoring. In many cases these practices differed
      significantly from the data sheet recommendations. These differences in stated
      practice could have financial and medicolegal as well as clinical implications.

PMID- 1352724
TI  - Inherited prion disease with 144 base pair gene insertion. 1. Genealogical and
      molecular studies.
AB  - Genealogical and molecular studies were carried out in four families in which
      early onset dementia is inherited as an autosomal dominant. These studies
      indicated that the four families derive from four siblings whose parents were
      born in the late 18th century in South-East England. The disease was found to be
      closely linked to a 144 bp insertion within the open reading frame of the prion
      protein (PrP) gene with a maximum LOD score of 11.02 at zero recombination.
      Within the general population the PrP gene is polymorphic at codon 129 (allele
      frequency approximately 30% valine, 70% methionine). The insertion in this family
      is always within a methionine-129 allele. The age at death of affected
      individuals whose normal allele encoded methionine at codon 129 was significantly
      lower than those whose normal allele encoded valine. The clinical features which
      were very variable and the neuropathological findings, which sometimes included
      spongiform encephalopathy, but which often did not, are described fully in the
      accompanying article (Collinge et al., 1992).

PMID- 1352725
TI  - Inherited prion disease with 144 base pair gene insertion. 2. Clinical and
      pathological features.
AB  - A large family with autosomal dominant segregation of presenile dementia, and
      other neurological and behavioural features is described. At various times,
      family members have carried diagnoses of Alzheimer's disease, Huntington's
      disease, Parkinson's disease, myoclonic epilepsy, atypical dementia, Pick's
      disease, Creutzfeldt-Jakob disease and Gerstmann-Straussler syndrome. Molecular
      genetic studies have enabled classification of this disease at the molecular
      level as one of the group of inherited prion diseases. Here we describe the
      phenotype of inherited prion disease (PrP 144 bp insertion).

PMID- 1352726
TI  - Behavioural analysis of unilateral monoamine depletion in the marmoset.
AB  - Unilateral stereotaxic injections of 6-hydroxydopamine (6-OHDA) into the
      nigrostriatal bundle of marmosets (Callithrix jacchus) produced substantial
      losses of tyrosine hydroxylase immunoreactive neurons from the substantia nigra,
      and mean dopamine (DA) depletions of 98-99% in the caudate nucleus, putamen and
      nucleus accumbens, and of 91-97% in frontal cortex, on the side of the lesion.
      Noradrenaline (NA) and 5-hydroxytryptamine (5-HT) levels were also affected.
      Behavioural tests conducted pre-operatively and at regular intervals during the 6
      mths following surgery revealed persistent deficits in the lesioned marmosets as
      a group compared with sham-lesioned controls, although individual marmosets
      sometimes recovered or showed no initial deficit on some tests. The main
      behavioural effects of the lesion were as follows: (i) an increase in the time
      spent with the head positioned ipsilaterally with respect to the rest of the
      body; (ii) ipsilateral spontaneous and amphetamine-induced rotation, although
      occasional intermittent periods of contralateral rotation and head biases were
      also recorded; (iii) contralateral apomorphine-induced rotation; (iv) reduced
      spontaneous activity; (v) ipsilateral hand preference on a conveyor belt task,
      although hand skill (measured as percentage errors when the speed of the belt was
      increased) was not affected; (vi) neglect of contralateral stimuli, both at the
      conveyor belt where lesioned monkeys often failed to respond on trials on which
      apple pieces arrived from the contralateral side, and on a test of sensorimotor
      neglect in which adhesive labels were placed around both feet. Comparisons of
      biochemical measures of the lesion with behavioural scores in individual monkeys
      suggest that DA depletions in excess of 95% are essential for long-term
      behavioural deficits.

PMID- 1352727
TI  - Effects of intravenous bicuculline and strychnine on inspiratory inhibitory
      responses in the cat.
AB  - Single shock stimulation of the superior laryngeal nerve (SLN), intercostal nerve
      (ICN), phrenic nerve (PN) or within the medullary respiratory groups (DRG-VRG)
      produces a transient, short-latency attenuation of inspiratory motor activity.
      Trains of stimuli delivered to SLN and ICN cause premature termination of
      inspiration. This study examined involvement of glycine and GABAA receptors in
      these reflex inhibitions. Experiments were conducted in decerebrate, vagotomized,
      and paralyzed cats. Control responses of left PN activity to threshold single
      shock stimulation of SLN, PN, ICN and the DRG-VRG were recorded and the
      thresholds for SLN- and ICN-evoked inspiratory termination were determined. Five
      min after intravenous injection of bicuculline (1 mg/kg) or strychnine (50
      micrograms/kg), the responses to stimulation were again recorded. This procedure
      was reiterated until the cumulative dose elicited marked convulsions. Neither
      drug affected the inspiratory terminating reflexes. Systemic bicuculline had no
      effect on transient inspiratory inhibition. However strychnine prolonged the
      onset latency and the duration of all four inhibitory responses. Since the degree
      of transient inhibition was not lessened (only delayed), it appears that these
      inspiratory inhibitory reflexes do not rely exclusively on actions of glycine or
      GABAA receptors.

PMID- 1352728
TI  - Flow thresholds for extracellular purine catabolite elevation in cat focal
      ischemia.
AB  - Ischemic glutamate excitotoxicity may be counteracted by adenosine which appears
      extracellularly during ischemia as an intermediate purine catabolite and has the
      potential to modulate glutamate release and its receptor action. The present
      study was conducted to evaluate the flow threshold for purine catabolite
      accumulation in relation to that for glutamate elevation in focal ischemia which
      was induced by middle cerebral artery (MCA) occlusion in halothane anesthetized
      cats. Assemblies of platinum electrodes and microdialysis probes were inserted
      into the somatosensory (SF, n = 13) and the auditory (A, n = 9) cortices to
      assess local cerebral blood flow (CBF) using hydrogen clearance and purine
      catabolite (adenosine, inosine and hypoxanthine) as well as glutamate
      concentrations in the dialysate using high-performance liquid chromatography
      (HPLC). In both investigated areas, purine catabolites were elevated if CBF fell
      below 25 ml/100 g/min, while glutamate increased at a flow threshold below 20
      ml/100 g/min. Maximum elevations of adenosine, inosine and hypoxanthine were 76-,
      29- and 11-fold, respectively, that of glutamate was 24-fold. In the range
      between 20 and 25 ml/100 g/min, significant increases of adenosine (5-15-fold)
      were measured, while glutamate did not markedly increase. The elevation of
      adenosine was transient whereas that of inosine, hypoxanthine and glutamate
      persisted over an ischemic period of 3 h. The higher flow threshold for adenosine
      may reflect an inherent but time limited protective mechanism against glutamate
      excitotoxicity.

PMID- 1352729
TI  - Sex differences in subregions of the medial nucleus of the amygdala and the bed
      nucleus of the stria terminalis of the rat.
AB  - Sex differences are described in subregions of two nuclei of the rat brain: the
      medical nucleus of the amygdala (MA) and the bed nucleus of the stria terminalis
      (BNST). The volume of the posterodorsal region of the medial nucleus of the
      amygdala (MApd) is approximately 85% greater and the volume of the encapsulated
      region of the bed nucleus of the stria terminalis (BNSTenc) is approximately 97%
      greater in males than in females. The MApd and BNSTenc are distinct subregions of
      the MA and BNST. They exhibit intense uptake of gonadal hormones and are
      anatomically connected to each other and to other sexually dimorphic nuclei. The
      MA and BNST in general are involved in regulation of several sexually dimorphic
      functions, including aggression, sexual behavior, gonadotropin secretion and
      integration of olfactory information. Precise localization of sex differences in
      subregions of the MA and BNST, such as the MApd and BNSTenc, may facilitate
      understanding of the neural basis of such functions.

PMID- 1352730
TI  - New therapies for ovarian cancer.

PMID- 1352731
TI  - [Fetal and neonatal effects of perimedullary opioids used in obstetrical
      anesthesia].
AB  - The use of spinal or epidural narcotics is more and more frequent in obstetric
      patients since it enhances the analgesia induced by local anesthetics. However,
      specific information regarding their fetal and neonatal effects is rare. Fetal
      effects are mainly dependent on the respiratory and hemodynamic maternal effects,
      and thus usually limited when usual low dosages of intraspinal narcotics are
      used. Neonatal respiratory depression, which is the main neonatal risk, has not
      been fully studied. In contrast, the evaluation of Apgar and neurobehavioral
      scores, performed for all the narcotics used, shows little changes when low
      dosages are used. However, the use of larger dosages epidurally is associated
      with an increased frequency of low neurobehavioral scores. Therefore, the use of
      low dosages of epidural narcotics is recommended since there is little available
      information about the risk of neonatal respiratory depression and no clear
      maternal advantage of higher dosages.

PMID- 1352733
TI  - Stress, agitation, and brain failure in critical care medicine.

PMID- 1352732
TI  - [Bolus esmolol prior to tracheal intubation of the elderly patient].
AB  - Twenty-seven patients 76 +/- 7 years old, ASA I or II, scheduled for short eye
      surgery, were randomized in two groups so as to study and compare the effects of
      esmolol--injected after induction of general anaesthesia, 2 or 3 mg.kg-1--or
      topic laryngeal anaesthesia on the haemodynamic consequences of endotracheal
      intubation. Induction was performed with fentanyl, thiopental and atracurium. The
      rate-pressure product was significantly lower (less than 11.000 b.min-1.mmHg-1)
      in the esmolol group. However 4 patients out of 5 who received the higher dosage
      of esmolol (3 mg.kg-1) had a marked blood pressure fall requiring ephedrine. A
      vascular collapse was observed in one of them but Buffington's ratio never fell
      under the critical value. In all cases small doses of ephedrine were efficient.
      No serious complications were observed in both groups. This preliminary study
      lacked a control group without esmolol or laryngeal spray. On the other hand,
      haemodynamic effects of tracheal intubation could be further studied after bolus
      esmolol or topic anaesthesia in real ASA III cardiovascular patients.

PMID- 1352734
TI  - The role of intercellular adhesion molecule-1 in chronic airway inflammation.
AB  - We have examined the role of intercellular adhesion molecule-1 (ICAM-1) in
      chronic airway inflammation and airway hyperresponsiveness in a primate model of
      asthma. Airway cellular composition was assessed by bronchoalveolar lavage (BAL)
      and airway responsiveness was measured as the bronchoconstrictor response to
      inhaled methacholine. In animals with chronic airway inflammation (increased BAL
      eosinophils) and sustained airway hyperresponsiveness, a 7 day dosing scheme with
      a murine anti-human ICAM-1 monoclonal antibody (R6.5, 2 mg/kg/day; i.v.) did not
      reduce the existing airway inflammation or airway hyperresponsiveness. In
      contrast, a similar dosing scheme with dexamethasone (0.2 mg/kg/day, i.m.) was
      found to significantly reduce both the airway eosinophilia and
      hyperresponsiveness. However, one week after cessation of dexamethasone
      treatment, the airway inflammation and hyperresponsiveness returned to pre
      treatment levels. In further experiments where animals were first treated with
      dexamethasone (7 days) followed by a 7 day treatment with R6.5, the reoccurrence
      of airway inflammation and subsequent increase in airway responsiveness was
      prevented. We conclude that the efficacy of ICAM-1 is primarily associated with
      inhibition of the influx of inflammatory cells into the airways and subsequent
      reduction in airway responsiveness. These data suggest that in lungs with pre
      existing inflammation the modulation of ICAM-1 following treatment with
      glucocorticoids may be a novel and more selective long-term treatment for control
      of the chronic airway inflammation and hyperresponsiveness associated with
      bronchial asthma.

PMID- 1352735
TI  - Medical management of hypertension in childhood.

PMID- 1352737
TI  - Abstracts of papers presented at the 39th European Organization for Caries
      Research (ORCA) Congress. Helsinki, June 24-28, 1992.

PMID- 1352738
TI  - Thapsigargin, an inhibitor of Ca(2+)-ATPase, antagonizes vacuole formation of
      hepatoma cells induced by teleocidin.

PMID- 1352736
TI  - Angiographic morphology in nonspecific aortoarteritis (Takayasu's arteritis): a
      study of 126 patients from north India.
AB  - We have studied the angiographic morphology of nonspecific aortoarteritis, or
      Takayasu's arteritis, in 126 patients who underwent total aortoarteriography by
      intravenous or intraarterial digital subtraction angiography (DSA). Steno
      obstructive lesions were seen in 124 (98.4%) patients and commonly involved the
      abdominal aorta (76.1%), the renal (67.5%), and the subclavian (56.3%) arteries.
      They were usually symptomatic. Aneurysms were seen in 16 (12.7%) patients and
      predominantly involved the descending thoracic aorta (62.5%). They were
      clinically silent. Localized saccular aneurysms (75%) were more common than the
      fusiform variety. Asymptomatic pulmonary artery involvement was seen in 11
      patients (n = 74; 14.9%). Right lung involvement (72.8%) was more common, usually
      as a stenosis or occlusion of a lobar branch in the upper zone. Intravenous DSA
      was usually adequate for establishing the diagnosis. In this population a
      distinct pattern of involvement and the young age at diagnosis were remarkable.

PMID- 1352739
TI  - Reversal of typical multidrug resistance by cyclosporin and its non
      immunosuppressive analogue SDZ PSC 833 in Chinese hamster ovary cells expressing
      the mdr1 phenotype.
AB  - The new non-immunosuppressive cyclosporin derivative SDZ PSC 833 (PSC) is a
      potent agent used to overcome typical multidrug resistance (MDR) associated with
      overexpression of the mdr1 gene encoding for a P-170 glycoprotein. In the present
      study, the efficacy of PSC as compared with cyclosporin was determined in Chinese
      hamster ovary cell lines exhibiting different levels of resistance to colchicine
      (0, 0.1, 0.2 and 10 micrograms/ml, respectively). Low concentrations of PSC (8.2
      nM) increased the cytotoxicity of colchicine in cell lines expressing low levels
      of drug resistance. The concentration resulting in 50% cell survival (LC50 value)
      found for colchicine alone or in combination with PSC in the CHO-A3 cell line
      that was resistant to 100 ng colchicine/ml decreased from greater than 500 to 200
      ng/ml at 8.2 nM PSC and to less than 100 ng/ml at 82 and 820 nM PSC. In the CHO
      A3 cell line that was resistant to 200 ng colchicine/ml, the LC50 values
      decreased from greater than 500 ng/ml for colchicine alone to 500 ng/ml for
      colchicine used in combination with 8.2 nM PSC and to less than 100 ng/ml for
      colchicine combined with 82 or 820 nM PSC. At a concentration of 82 nM PSC, the
      maximal effect in MDR reversal was observed in the cell lines exhibiting moderate
      resistance. In the highly resistant cell line, PSC (820 nM) also reversed
      colchicine resistance. In drug-accumulation experiments, we obtained a 4-fold
      increase in intracellular doxorubicin accumulation using 820 nM PSC. A comparison
      of PSC with cyclosporin revealed that a cyclosporin concentration 20-fold that of
      PSC was required to obtain the same sensitising effect. On the basis of these
      data, it may be concluded that PSC is a most promising chemosensitiser.

PMID- 1352740
TI  - Proliferating cell nuclear antigen (PCNA/cyclin) in plant proliferating cells:
      immunohistochemical and quantitative analysis using autoantibody and murine
      monoclonal antibodies to PCNA.
AB  - Proliferating-cell nuclear antigen (PCNA), also known as cyclin, is synthesized
      in proliferative cells and recently was identified as DNA polymerase-delta
      auxiliary protein. In this paper, the association of PCNA to the proliferative
      cells of plants was analysed using both autoantibodies to PCNA obtained from a
      patient with systemic lupus erythematosus (SLE) and murine monoclonal antibodies.
      By immunohistochemical analysis, nuclei of cells around the growing point in
      soybean root tips reacted strongly with autoantibodies to PCNA in the serum from
      a patient with SLE. The plant PCNA in root tip cells was purified by ammonium
      sulfate fractionation, DEAE chromatography, and affinity chromatography. The
      partially purified plant PCNA was tested by immunoblotting and a 34 kD
      polypeptide reacted with both the human anti-PCNA autoantibody and a mouse
      monoclonal antibody against human PCNA (TOB 7). In addition, the purified plant
      PCNA reacted with both antibodies in enzyme-linked immunosorbent assay (ELISA).
      The binding of anti-PCNA serum to the animal PCNA was blocked by the plant PCNA
      in this ELISA. The association of PCNA with growing cells in plants was further
      confirmed by quantitative sandwich type ELISA using two murine monoclonal
      antibodies to PCNA, TOB7 and TO17. Those results suggested that PCNA in both
      plant and animal cells had the same immunological and biochemical characteristics
      and the plant PCNA might play an important role in cell growth, existing as it
      does in proliferating plant cells. The concentration of PCNA in soybean germ
      extract before germination was less than 5 ng ml-1 (protein concentration, 6.8 mg
      ml-1), but that of the root tip stem including the growing point increased to 887
      ng ml-1 (protein concentration 3.8 mg ml-1) in the second day after germination.

PMID- 1352741
TI  - Mechanisms of subendocardial dysfunction in response to exercise in dogs with
      severe left ventricular hypertrophy.
AB  - The effects of exercise on regional myocardial blood flow and function were
      examined in the presence and absence of beta-adrenergic receptor blockade in 10
      adult conscious dogs with severe left ventricular (LV) hypertrophy induced by
      aortic banding in puppies, which increased the LV weight/body weight ratio by
      87%. Exercise at the most intense level studied increased LV systolic (+87 +/- 8
      mm Hg) and end-diastolic (+28 +/- 5 mm Hg) pressures, systolic (+85 +/- 12 g/cm2)
      and diastolic (+49 +/- 11 g/cm2) wall stresses, and subepicardial wall thickening
      (+0.18 +/- 0.05 mm) but reduced subendocardial wall thickening (-0.45 +/- 0.12
      mm) and full wall thickening (-0.42 +/- 0.13 mm). This was associated with a fall
      in the subendocardial/subepicardial (endo/epi) blood flow ratio to 0.87 +/- 0.06
      from 1.24 +/- 0.08. Subendocardial dysfunction persisted during recovery, at a
      time when transmural blood flow distribution returned to baseline, suggesting
      myocardial stunning. At the least intense level of exercise studied, the endo/epi
      blood flow ratio did not fall (1.27 +/- 0.14), but increases in heart rate (+73
      +/- 8 beats per minute) and LV systolic (+35 +/- 8 g/cm2) and diastolic (+27 +/-
      3 g/cm2) wall stresses were observed, and subendocardial wall thickening fell
      significantly (-0.21 +/- 0.08 mm, p less than 0.05). With anticipation of
      exercise, subendocardial wall thickening was not changed. However, subendocardial
      dysfunction was even evident after 10 beats, i.e., the first 3 seconds of
      exercise, at a time when LV pressures and stresses had not increased. After beta
      adrenergic receptor blockade with propranolol, the most intense level of exercise
      was associated with lesser increases in systolic and diastolic LV wall stresses,
      heart rate, and LV dP/dt, and the endo/epi blood flow ratio was no longer reduced
      below unity (1.17 +/- 0.09). In addition, there were no decreases in
      subendocardial or full wall thickening, and myocardial stunning was no longer
      observed. Thus, the subendocardial hypoperfusion and depression in subendocardial
      wall thickening observed during exercise in dogs with LV hypertrophy was
      prevented by pretreatment with beta-adrenergic receptor blockade. Furthermore,
      the subendocardial dysfunction occurred rapidly, before alterations in LV
      systolic or diastolic wall stress or an alteration in the endo/epi blood flow
      ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1352742
TI  - An impairment of renal tubular DA-1 receptor function as the causative factor for
      diminished natriuresis to volume expansion in spontaneously hypertensive rats.
AB  - It has been demonstrated that endogenous kidney dopamine (DA) contributes to the
      natriuretic response to acute volume expansion (VE). Several studies suggest that
      a defect in renal DA-ergic mechanism may play a role in genetic hypertension in
      humans and rats. The present study was designed to determine the role of renal DA
      and tubular DA-1 receptors in the natriuretic response to VE in age-matched
      spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats of 10-12 weeks
      of age. In pentobarbital-anesthetized rats, VE was carried out by intravenously
      infusing isotonic sodium chloride (5% body weight) over a period of 60 min. This
      maneuver evoked pronounced increases in urine output, urinary sodium excretion
      and urinary DA excretion. However, the natriuretic and diuretic response to VE
      was significantly reduced in SHR, although the increase in urinary DA excretion
      was similar in both SHR and WKY rats. During VE no significant changes in
      glomerular filtration rate or blood pressure were noted in either strain of
      animals, indicating the involvement of renal tubular mechanisms in the
      natriuretic response. In a separate group of SHR and WKY rats, pretreatment with
      DA-1 receptor antagonist SCH 23390 caused significant attenuation of the
      natriuretic and diuretic response to VE in WKY rats but not in SHR, suggesting
      that unlike WKY rats kidney DA was not contributing to the natriuretic response
      to VE in SHR. In another group of animals, the renal effects of exogenously
      administered DA-1 receptor agonist fenoldopam were examined. Fenoldopam (1
      microgram/kg/min) produced significant increases in urine output and urinary
      sodium excretion without causing any alterations in blood pressure or glomerular
      filtration rate in both SHR and WKY rats. However, the interesting observation
      was that fenoldopam-induced diuresis and natriuresis were significantly
      attenuated in SHR compared to the WKY rats. These results show that SHR are not
      able to eliminate an acute increase in sodium load as efficiently as WKY rats,
      which may be at least in part due to a defect in renal tubular DA-1 receptor
      function.

PMID- 1352743
TI  - DA1 receptor mediated regulation of Na(+)-H+ antiport activity in rat renal
      cortical brush border membrane vesicles.
AB  - Our previous studies indicate that dopamine (DA) plays an important role in
      regulating renal sodium (Na+) metabolism during high Na+ intake, and that DA1
      receptors are involved in natriuretic response to acute volume expansion. It has
      also been shown that in addition to the changes in renal hemodynamics, the
      natriuretic response produced by exogenously administered DA and DA1 receptor
      agonists appears to be due to alterations in renal tubular sodium transport
      mechanisms. This study was designed to investigate the DA1 receptor-mediated
      changes in Na(+)-H+ antiport activity in tubular brush border membranes of rat
      kidney. The Na(+)-H+ antiport activity, measured as the amiloride-sensitive Na+
      influx in BBMV, was inhibited by 37%, 46%, 33%, and 42% by 1 microM DA, SKF
      82958, SKF 38393, and fenoldopam respectively. The DA1 antagonist SCH 23390
      increased the antiport activity when given alone, while when administered with an
      agonist it attenuated the effects of the agonist on the antiporter. DA2 agonists
      and antagonists failed to affect the antiport activity. These results indicate
      that the inhibitory effects of DA and DA receptor agonists on Na(+)-H+ antiport
      activity in renal cortical BBMV were mediated by the DA1 receptors.

PMID- 1352744
TI  - Chronic cardiovascular effects of central vasopressin in conscious rats.
AB  - To clarify the cardiovascular effects of central vasopressin (AVP), a chronic
      intracerebroventricular (ICV) infusion of AVP was performed in conscious Wistar
      normotensive rats. Animals were divided into 3 groups: 1) AVP 1 ng/hr (Low), 2)
      AVP 100 ng/hr (High), and 3) saline (control) ICV infusion. After a 6 day control
      period, AVP or saline was continuously infused into the lateral cerebroventricle
      at a rate of 1 microliter/hr using osmotic minipump for 7 days. As a result, a
      dose-related elevation of AVP concentration in CSF was achieved. Systolic blood
      pressure in both Low and High AVP infusion was slightly (7-12 mmHg) but
      significantly higher than that in control. ICV infusion of AVP did not alter
      urine volume, electrolytes excretion or osmolality, and AVP vascular antagonist
      injected intravenously failed to affect mean arterial pressure. Furthermore,
      plasma catecholamines and renin activity did not differ significantly among the
      groups. Thus, chronic ICV infusion of AVP induced the elevation of blood
      pressure, which is due to centrally mediated effect of AVP.

PMID- 1352745
TI  - Normal C3b receptor (CR1) genomic polymorphism in patients with insulin-dependent
      diabetes mellitus (IDDM): is the low erythrocyte CR1 expression an acquired
      phenomenon?
AB  - Expression of the erythrocyte complement receptor (C3bR = CR1 = CD35) and its
      genomic polymorphism (HindIII RFLP) was studied in a group of 80 patients with
      IDDM, 31 healthy siblings and 101 healthy blood donors. Defective CR1 expression
      was found in 26% of the patients with IDDM compared with 9% of the controls (P
      less than 0.05) and 0% of the siblings. The CR1 gene polymorphism of the IDDM
      patients did not significantly differ from that of the controls. The presence of
      a 6.9 kb (L) CR1 gene fragment was associated with a low CR1 expression in the
      patients (P less than 0.05) and especially in the controls (P less than 0.001).
      No significant association was found between the presence or absence of the HLA
      risk antigens for IDDM and CR1 expression. The results confirm that erythrocyte
      CR1 expression is genetically determined, but the CR1 deficiency associated with
      IDDM seems to be an acquired rather than a genetic phenomenon.

PMID- 1352746
TI  - Increased frequency of the long (S) allotype of CR1 (the C3b/C4b receptor, CD35)
      in patients with systemic lupus erythematosus.
AB  - The allotypic forms of the C3b/C4b receptor (CR1, CD35) differ in length, in the
      number of expressed C3b binding sites and thus in their ability to mediate the
      processing of circulating C3- and C4-bearing immune complexes. We have used a
      combination of three informative restriction fragment length polymorphisms
      (RFLPs) to assess the frequencies of the F (most frequent allele comprised of
      four long homologous repeats (LHR)), S (five LHR) and F' (three LHR) alleles of
      the C3b/C4b receptor (CR1, CD35) in a French population of patients with systemic
      lupus erythematosus (SLE) (n = 63) and healthy controls (n = 158). A
      significantly higher frequency of the S phenotype was observed among patients
      (51%) as compared with controls (26%). The F' allele was found in 2/61 patients
      and 1/85 healthy controls, indicating the rare occurrence of the short CR1 allele
      in SLE. This allele is also extremely rare in the normal population. The
      overrepresentation of the S long allele among patients is indicative of a genetic
      linkage between CR1 and susceptibility to SLE.

PMID- 1352747
TI  - Circulating intercellular adhesion molecule-1 (ICAM-1) antigen in sera of
      patients with idiopathic pulmonary fibrosis.
AB  - Intercellular adhesion molecule-1 (ICAM-1), a member of immunoglobulin supergene
      family with a five-domain structure, is known to play an important role in
      inflammatory diseases. An ELISA was developed using two MoAbs against human ICAM
      1 in order to detect the soluble shedding ICAM-1 antigen in sera. We measured
      levels of circulating ICAM-1 antigen in sera of patients with idiopathic
      pulmonary fibrosis (IPF), pulmonary sarcoidosis, hypersensitive pneumonitis,
      bacterial and mycoplasmal pneumonia, and inflammatory diseases of other organs.
      The results clearly demonstrated that IPF had significantly high levels of
      circulating ICAM-1 in sera as compared with other disorders or normal controls.
      Moreover, immunohistochemical analysis with MoAb against human ICAM-1 disclosed
      that in IPF, the expression of ICAM-1 was intensively enhanced on alveolar
      epithelial cells. These results suggest that ICAM-1 may contribute to the
      pathogenesis of IPF.

PMID- 1352748
TI  - Spontaneous development of pancreatitis in the MRL/Mp strain of mice in
      autoimmune mechanism.
AB  - MRL/Mp mice are known to have autoimmune disease-prone genetic background, which
      contributes to the development of a lethal autoimmune disease at an early age in
      association with the lymphoproliferative gene, lpr. In this study, we found that
      MRL/Mp mice, not bearing lpr (MRL/Mp-(+)/+), spontaneously developed pancreatitis
      at a late stage of life, which was histopathologically characterized by
      destruction of pancreatic acinar cells with mononuclear cell infiltration. In
      female 34-38-weeks-old mice the incidence of pancreatitis reached 74%, whereas
      the male mice developed the disease with a reduced incidence, at a later stage of
      life and with a reduced severity. Cell infiltrates in the affected lesions were
      composed predominantly of CD4+ cells and to lesser extent Mac-2+ macrophages.
      Adoptive transfer of the spleen cells obtained from pancreatitis-bearing female
      mice generated pancreatitis in female normal mice, but not in the male mice.
      Transfer of the serum of pancreatitis-bearing mice failed to induce any
      pancreatic lesions. These findings indicate that pancreatitis in MRL/Mp-(+)/+
      mice may be mediated by cellular autoimmune mechanism. This may present a useful
      concept for analysis of the developmental mechanisms of human chronic
      pancreatitis in an aspect of autoimmunity.

PMID- 1352749
TI  - [Neuromyopathy induced by halothane anesthesia and muscle relaxants for status
      asthmaticus--report of 2 patients].
AB  - Two patients with status asthmaticus (a 30-year-old female and a 48-year-old
      male) who developed flaccid quadriplegia and sensory impairment of glove and
      stocking type after treatment with halothane, muscle relaxants (pancuronium and
      vecuronium) and steroid are described. They noted motor and sensory impairment
      immediately after recovery from control ventilation for treatment of status
      asthmaticus. Histochemical examinations of biopsied muscle demonstrated the
      necrosis and regeneration of muscle fibers and small diameters in type I fibers.
      These results suggested that the involvement of muscle (myopathy) was a
      consequence of the harmful action of halothane and muscle relaxants together with
      steroids on muscle fibers with subclinical fragility. The sensory impairment
      (neuropathy) was considered to have been produced mainly by the halothane
      together with muscle relaxants and aminoglycosides.

PMID- 1352750
TI  - Toward a chronotherapy of ovarian cancer with taxol. Part II: Test pilot study on
      circulating CA125.

PMID- 1352751
TI  - Rash promises for topical antihistamines.

PMID- 1352752
TI  - Effects of hyperoxia and beta-adrenergic stimulation on pulmonary surfactant in
      neonatal rabbits.
AB  - To study the effects of hyperoxia and beta-adrenergic stimulation on pulmonary
      surfactant in the neonatal lung, we measured disaturated phosphatidylcholine
      (DSPC) and [14C]choline incorporation into DSPC, obtained from alveolar lavage
      and lung tissue. We used an isolated salt-perfused rabbit lung preparation from
      neonatal rabbits exposed to room air or greater than 95% oxygen for 3 days. There
      were four experimental groups: room air, basal condition; room air, beta
      adrenergic stimulation; hyperoxia, basal conditions; and hyperoxia, beta
      adrenergic stimulation. Hyperoxia caused a significant decrease in lavage and
      intracellular [14C]DSPC specific activity, and a decrease in intracellular DSPC
      suggesting depressed surfactant synthesis. Beta-stimulation in room air caused a
      decrease in lavage DSPC, an increase in DSPC, and [14C]DSPC fraction released,
      consistent with increased uptake for reutilization. With hyperoxia and beta
      stimulation, there is an increase in total DSPC in the lavage; lavage [14C]DSPC
      specific activity is similar to that of the basal hyperoxia group (i.e.,
      depressed compared with the room air state); intracellular [14C]DSPC specific
      activity does not differ from basal, hyperoxia, or beta-stimulated, room air
      groups, all being depressed compared with basal, room air conditions.
      Intracellular DSPC in the beta-stimulated group is less affected by hyperoxia
      than the basal groups. It appears that prolonged exposure to hyperoxia is
      manifested primarily by a decrease in [14C]DSPC specific activity suggesting
      alterations in surfactant synthesis, though DSPC in the lavage is not altered.
      Beta-adrenergic stimulation may enhance release of newly synthesized surfactant
      into the alveoli, and possibly enhances uptake for reutilization. The enhancement
      of surfactant release seems to be preserved after prolonged hyperoxia.

PMID- 1352753
TI  - Paper symposium: Immobilized pH gradients II.

PMID- 1352756
TI  - Homeobox genes and pattern formation in the vertebrate limb.
AB  - The developing vertebrate limb is a powerful system to study genes potentially
      involved in pattern formation. Many such candidate genes encode transcription
      factors belonging to the class of the "homeodomain" proteins. In this short
      review, we discuss the possible functions of different subfamilies of homeobox
      genes. Genes belonging to the Hox family (related to the Drosophila homoeotic
      genes), such as the HOX-1, HOX-3, and HOX-4, complexes are probably among those
      encoding the patterning information. Their differential expression in the
      mesenchymal compartment is proposed to be responsible for the determination of
      the various axial elements. Other homeobox-containing genes are expressed in both
      the mesenchyme of the progress zone and the ectodermal ridge. These genes, Hox
      7.1 and Hox-8.1, are related to the Drosophila msh gene and could be involved in
      epithelial-mesenchymal interactions linking the growth of the system to its
      patterning.

PMID- 1352754
TI  - Two vertebrate homeobox genes related to the Drosophila empty spiracles gene are
      expressed in the embryonic cerebral cortex.
AB  - We cloned two homeobox genes, Emx1 and Emx2, related to empty spiracles, a gene
      expressed in very anterior body regions during early Drosophila embryogenesis,
      and studied their expression in mouse embryos. Emx1 expression is detectable from
      day 9.5 of gestation whereas Emx2 appears to be already expressed in 8.5 day
      embryos. Both genes are expressed in the presumptive cerebral cortex and
      olfactory bulbs. Emx1 is expressed exclusively there, whereas Emx2 is also
      expressed in some neuroectodermal areas in embryonic head including olfactory
      placodes in earlier stages and olfactory epithelia later in development.

PMID- 1352755
TI  - Characterization of the Lactococcus lactis pepN gene encoding an aminopeptidase
      homologous to mammalian aminopeptidase N.
AB  - The nucleotide sequence of the pepN gene from Lactococcus lactis encoding a zinc
      metallo aminopeptidase has been determined. The open reading frame of 2,538 base
      pairs encodes a protein with a calculated M(r) of 95,368, which agrees with the
      apparent M(r) of 95,000 of the gene product which was identified by polyclonal
      antibodies raised against the purified aminopeptidase. The amino acid sequence of
      the aminopeptidase of L. lactis was found to be similar to the corresponding
      enzymes of human, rat and mouse, with almost 30% of the residues identical. Also,
      a highly conserved area was identified which has similarity with the active site
      of thermolysin. A zinc-binding site, as well as the catalytic site for PepN, is
      predicted to lie within this conserved stretch. Putative promoter regions
      upstream of PepN were confirmed by primer extension analysis.

PMID- 1352757
TI  - Retinoid receptors in vertebrate limb development.
AB  - Although the precise role of retinoids in limb development remains obscure, the
      finding that retinoic acid can produce major alterations in limb patterning
      suggests that this ligand might be involved in the process of limb morphogenesis.
      Here we describe the patterns of expression of retinoic acid receptors and
      cytosolic retinoid binding proteins during the course of limb morphogenesis.
      Examining the distribution of these molecules in the limb and correlating their
      presence with important processes in limb development could help elucidate their
      possible functions.

PMID- 1352758
TI  - Molecular cloning of a gene (cfp) encoding the cytoplasmic filament protein P59Nc
      and its genetic relationship to the snowflake locus of Neurospora crassa.
AB  - P59Nc is a 59-kD polypeptide associated with 8-10-nm diameter cellular filaments
      in normal Neurospora crassa strains. Abnormally sized and shaped bundles of these
      structures are present in N. crassa strains carrying mutations at the locus sn
      (snowflake). By using molecular cloning and restriction fragment length
      polymorphism (RFLP) segregation analysis strategies we show here that sn is not
      the genetic locus of P59Nc. Several P59Nc cDNAs were cloned from a N. crassa
      lambda GT11 library after immunoscreening with specific polyclonal anti-P59Nc
      antibodies. Additional longer cDNAs were obtained from a N. crassa cDNA-lambda
      ZAP library. When used as probes in Southern blots of total DNA from wild-type
      strains, multicent-2 (a multiple mutant strain), and snowflake mutants, the P59Nc
      cDNAs revealed comparable patterns of hybridizing bands for all of the
      restriction enzymes tested. Analysis of segregation of BclI and ClaI RFLPs,
      detected in the genomic region of the P59Nc gene (locus cfp: cellular filament
      polypeptide), among a set of strains designed for RFLP mapping, or among selected
      progeny of crosses involving a snowflake parent, respectively, indicate that (i)
      there is in N. crassa a single cfp locus positioned on the right arm of linkage
      group VII between the locus for and the proximal breakpoint of the translocation
      T(VII----I)5936; (ii) the sn mutations in the centromere region of chromosome I
      do not represent translocations of cfp; and (iii) the snowflake mutants possesses
      a normal copy of the P59Nc gene on their chromosomes VII.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1352759
TI  - A molecular marker-based linkage map of Phaseolus vulgaris L.
AB  - A seed and flower color marker (P), nine seed protein, nine isozyme and 224
      restriction fragment length polymorphism marker loci were used to construct a
      linkage map of the common bean, Phaseolus vulgaris L. (n = 11). The mapping
      population consisted of a backcross progeny between the Mesoamerican breeding
      line 'XR-235-1-1' and the Andean cultivar 'Calima'; the former was used as the
      recurrent parent. A bean PstI genomic library enriched for single copy sequences
      (95%) was the source of DNA probes. Sixty percent of the probes tested detected
      polymorphisms between the parental genotypes with at least one of the four
      restriction enzymes used here (DraI, EcoRI, EcoRV and HindIII). The computer
      software Mapmaker was used to determine the linkage relationships and linear
      order of segregating markers. These markers assorted into 11 linkage groups
      covering 960 cM of the bean genome. Partial linkage data were used to estimate
      the total length of the genome at 1200 cM. This estimate and that for the
      physical size of the genome yield an average ratio of 530 kb/cM. The relatively
      small size of the genome makes this crop species a good candidate for the
      isolation of genes via chromosome walking techniques.

PMID- 1352760
TI  - Two isoforms of the kidney androgen-regulated protein are encoded by two alleles
      of a single gene in OF1 mice.
AB  - Two cDNA clones coding for two forms of the mouse kidney androgen-regulated
      protein (KAP) distinguished by their electrophoretic mobilities on SDS gel
      electrophoresis have been isolated from libraries prepared from strains of mice
      having one (BALB/c) or two (OF1) forms of the KAP protein. The corresponding
      mRNAs have identical sizes, as well as identical sequences in their 5' non
      translated regions. The size difference observed between the two proteins is due
      to two point mutations in the coding region of the KAP mRNA, leading to two amino
      acid changes one of which resulted in the substitution of a glycine for a
      glutamic acid. As shown by in vitro transcription/translation experiments, these
      two amino-acid differences are responsible for the shift in the apparent
      molecular weight of the protein on SDS gels. Both forms of the protein are more
      abundant in males than in females. In vitro translation of kidney RNAs isolated
      from six different strains and species of mice revealed the presence of other
      forms of the KAP protein, characterized by small variations of their molecular
      weights. Southern blot analysis data are consistent with the presence of only one
      kap gene in the mouse genome. A restriction fragment length polymorphism has been
      observed, which does not correlate with the protein polymorphism, indicating the
      presence of another allele in the OF1 mouse genome.

PMID- 1352761
TI  - Homology of TcpN, a putative regulatory protein of Vibrio cholerae, to the AraC
      family of transcriptional activators.
AB  - The nucleotide sequence has been determined for the gene designated tcpN,
      encoding a putative regulatory protein within the tcp gene cluster associated
      with the biosynthesis and assembly of the toxin-coregulated pilus of Vibrio
      cholerae. It is preceded by a powerful transcriptional terminator which
      presumably delimits the major tcp operon, but at its 3' end is translationally
      coupled to the gene, tcpJ, encoding the TCP pilin signal peptidase. The tcpN gene
      encodes a putative 276-residue protein of 31,890 Da. This TcpN shows a high
      degree of homology to the transcriptional activators, Rns, associated with pilus
      biosynthesis in enterotoxigenic Escherichia coli, and to VirF, which controls the
      Yersinia virulence regulon. This homology also extends to the C termini of other
      members of the AraC family of transcriptional regulators, including RhaS, RhaR
      and CelD.

PMID- 1352762
TI  - Glutamate accumulation and increased hydroxyl free radical formation in the
      abdominal aorta and heart of gerbil after ischemia/reperfusion insult.
AB  - The concentration of glutamate as well as the hydroxylation of salicylate, as an
      index of hydroxyl free radical formation, has been determined in the abdominal
      aorta and heart of gerbils undergoing an ischemia/reperfusion insult (IRI) and
      compared to control sham-operated gerbils. The amount of glutamate and
      hydroxylated salicylate (dihydroxybenzoic acid, DHBA) was significantly increased
      in both the aorta and heart of IRI-treated gerbils as compared to the aorta and
      in the heart of sham-operated gerbils. Vitamin E (90 mg/kg at 24 and 1 h prior to
      an IRI) pretreatment prevented the increase of both glutamate and DHBA in both
      the aorta and heart of IRI-lesioned gerbils. The results suggest that increases
      in glutamate, perhaps due to the decreased activities of glutamine synthetase,
      are correlated with increased oxygen free radical formation during an
      ischemia/reperfusion insult to the heart.

PMID- 1352763
TI  - [Franz-Gross-Hypertension-Symposium. Regulation of myocardial cells on the
      molecular level, pharmacological and clinical implications. Kronberg, 5-7 March
      1992].

PMID- 1352765
TI  - [Heparin-induced thrombosis-thrombocytopenia syndrome in Crohn disease. Further
      thromboses with oral anticoagulation after discontinuation of heparin].

PMID- 1352764
TI  - Human CD4+ T cells expressing CD45RA acquire the lymphokine gene expression of
      CD45RO+ T-helper cells after activation in vitro.
AB  - CD4+ T cells were separated into subpopulations according to their expression of
      different isoforms of the CD45R molecule, i.e. CD45RA and CD45RO. The separated
      cells were activated with staphylococcal enterotoxin A (SEA) in the presence of
      formalin fixed Raji cells. Each set of cells was activated twice with a 6-day
      interval, and the lymphokine gene expression during the first 3 days after
      initiation of each stimulation was followed by use of polymerase chain reaction
      (PCR) technology. The lymphokine messenger RNA (mRNA) profiles were found to
      differ between the subsets, since after the first stimulation the CD45RA+ cells
      produced mRNA encoding interleukin-2 (IL-2) and IL-1 alpha, whereas the CD45RO+
      cells transcribed genes for IL-1 alpha, IL-2, IL-4, IL-5 and interferon-gamma
      (IFN-gamma). After 6 days of SEA stimulation both populations were mainly CD45RO
      reactive, and when restimulated displayed the lymphokine mRNA profile restricted
      to this subset. These results indicate that the CD45RA subset is a precursor of
      the CD45RO and further strengthen the hypothesis that the former cell population
      represents naive whereas the latter subset represents memory T cells within the
      CD4 subset.

PMID- 1352766
TI  - Cleft palate symposium--the Children's Hospital Temple St--10th January 1992.

PMID- 1352767
TI  - Appraisal and reappraisal of clinical methods: Valsalva manoeuvre.

PMID- 1352768
TI  - Proteolytic processing of the mosquitocidal toxin from Bacillus sphaericus SSII
      1.
AB  - The 97-kDa protein Mtx21, derived from the 100-kDa mosquitocidal protein (Mtx)
      from Bacillus sphaericus SSII-1 by the deletion of the putative signal sequence,
      was expressed as a fusion protein with glutathione S-transferase in Escherichia
      coli, and the fusion protein was purified by affinity chromatography. The fusion
      protein bound to glutathione agarose was cleaved with thrombin to release the
      Mtx21 protein. The 97-kDa Mtx21 protein was found to be toxic to Culex
      quinquefasciatus larvae with a 50% lethal concentration of 15 ng/ml. Treating
      Mtx21 with crude mosquito larval gut extracts gave rise to two major peptides of
      70 and 27 kDa. Treating the 97-kDa Mtx21 protein with trysin also gave rise to a
      similar proteolytic cleavage pattern. N-terminal sequencing showed that the 27
      kDa peptide was derived from the N-terminal region of the 97-kDa protein and that
      the 70-kDa protein was from the C-terminal region of the 97-kDa protein. The 27
      kDa peptide has all the previously identified regions of homology with the
      catalytic peptides of the ADP-ribosyltransferase toxins, such as pertussis toxin
      S1 peptide, while the 70-kDa peptide has three internal regions of homology.

PMID- 1352769
TI  - Evidence that GroEL, not sigma 32, is involved in transcriptional regulation of
      the Vibrio fischeri luminescence genes in Escherichia coli.
AB  - In Escherichia coli, transcription of the inducible Vibrio fischeri luminescence
      operon, luxICDABE, has been reported to require sigma 32, the product of rpoH.
      Consistent with previous studies, we report that an E. coli delta rpoH mutant,
      KY1601 containing luxICDABE and luxR, which codes for the activator of luxICDABE
      transcription on a plasmid (pJE202), was weakly luminescent. Transformation of
      this E. coli strain with a plasmid containing rpoH under the control of the tac
      promoter resulted in high levels of cellular luminescence. However, the level of
      expression of the pJE202 luxICDABE was also high in E. coli 1603, a delta rpoH
      mutant with a second-site mutation that resulted in sigma 32-independent
      overexpression of the groE operon. Apparently, sigma 32 is not directly required
      for the transcription of luxICDABE in E. coli but is required for sufficient
      expression of groE, which is in turn required for the transcription of luxICDABE.
      This conclusion is supported by the finding that E. coli groE mutants containing
      pJE202 were weakly luminescent. In the E. coli delta rpoH mutant KY1601, the
      sigma 32 requirement for the transcription of luxICDABE was partially compensated
      for by the addition of saturating concentrations of the inducer to the culture
      medium and largely compensated for when cells were transformed with a luxR
      overexpression vector. These data support the hypothesis that sigma 32 is not
      required for transcription of luxICDABE. Rather, it appears that the products of
      groE are required for the folding of LuxR into an active protein, like they are
      for the folding of several other proteins.

PMID- 1352770
TI  - Glycerol-induced unraveling of the tight helical conformation of Escherichia coli
      type 1 fimbriae.
AB  - Glycerol was found to unravel the helical conformation of Escherichia coli type 1
      fimbriae without appreciable depolymerization. The linearized fimbrial polymers
      have a diameter of 2 nm, react strongly with a monoclonal antibody directed at an
      inaccessible epitope on native fimbriae, and display greater mannose-binding
      activity and trypsin sensitivity than native fimbriae. Removal of glycerol by
      dialysis results in spontaneous reassembly of the linear polymers into structures
      morphologically, antigenically, and functionally indistinguishable from native
      fimbriae.

PMID- 1352771
TI  - Proline biosynthesis in Saccharomyces cerevisiae: analysis of the PRO3 gene,
      which encodes delta 1-pyrroline-5-carboxylate reductase.

PMID- 1352772
TI  - Biochemical comparisons of the normal and oncogenic forms of insect cell
      expressed neu tyrosine kinases.
AB  - The rat neu oncogene product is a member of the epidermal growth factor (EGF)
      receptor subgroup of the superfamily of growth factor receptor tyrosine kinases.
      The oncogenic activation of the neu protein occurs by a point mutation within its
      transmembrane region which results in an increase in its tyrosine kinase
      activity. Using three different forms of neu expressed in insect cells via
      baculovirus infection, we have examined the biochemical differences between the
      normal and transforming forms of neu and investigated the role of the
      transmembrane domain in its tyrosine kinase activity. One form of neu which was
      expressed in insect cells consisted of the complete tyrosine kinase domain but
      lacked the extracellular and transmembrane regions (designated NTK). The other
      two forms consisted of the tyrosine kinase domain, the transmembrane domain, and
      40 amino acids of the extracellular domain. One of these transmembrane forms of
      neu contained the normal valine residue at position 664 within the transmembrane
      region (MS-N), while the other contained the oncogenic glutamic acid residue at
      this position (MS-T). Direct comparisons of NTK, MS-N, and MS-T have shown that
      the NTK protein is capable of the highest extents of both autophosphorylation
      activity and the tyrosine phosphorylation of exogenous substrate, suggesting that
      the presence of the transmembrane region of neu suppresses the tyrosine kinase
      activity of this receptor. In addition, we have found that the oncogenic point
      mutation within the transmembrane region stimulates the tyrosine kinase activity
      of the neu protein by allowing it to more effectively utilize Mg2+. Overall, the
      results of these studies suggest that the valine to glutamic acid substitution at
      position 664 may at least partially relieve a negative constraint imparted by the
      membrane-spanning domain on the tyrosine kinase activity of neu and enables a
      more effective use of Mg2+ in the catalysis of tyrosine phosphorylation of
      exogenous substrates.

PMID- 1352773
TI  - A new member of the natriuretic peptide family is present in the venom of the
      green mamba (Dendroaspis angusticeps).
AB  - This paper describes the purification, sequence, and biological properties of a
      38-amino acid residue peptide from the venom of Dendroaspis angusticeps which
      shared important sequence homologies with natriuretic peptides. Dendroaspis
      natriuretic peptide (DNP) relaxed aortic strips that had been contracted by 40 mM
      KCl with a potency (K0.5 = 20 nM) similar to that of atrial natriuretic peptide
      (ANP) and larger than that of C type natriuretic peptide (CNP). The relaxing
      actions of ANP and DNP (both at 100 nM) were mutually exclusive. Bovine aortic
      endothelial cells responded to ANP (K0.5 = 3 nM) and DNP (K0.5 = 3 nM) but not to
      CNP by a large activation of guanylate cyclase. Rat aortic myocytes showed larger
      cGMP responses to CNP (K0.5 = 10 nM) than to ANP or DNP (K0.5 = 100 nM). Finally,
      DNP completely prevented the specific 125I-ANP binding to clearance receptors in
      cultured aortic myocytes with a potency (Kd = 10 nM) that was less than that of
      ANP (Kd = 0.3 nM). It is concluded that DNP is a new member of the family of
      natriuretic peptides and that it recognizes ANPA receptors and clearance, ANPc
      receptors, but not CNP-specific ANPB receptors.

PMID- 1352774
TI  - Anion-proton cotransport through the human red blood cell band 3 protein. Role of
      glutamate 681.
AB  - The band 3 protein of the human red blood cell membrane contains a glutamate
      residue that must be protonated in order for divalent (SO4=) anion transport to
      take place at an appreciable rate. The carboxyl side chain on this glutamate
      residue can be converted to the primary alcohol by treatment of intact cells with
      Woodward's reagent K (N-ethyl-5-phenylisoxazolium 3'-sulfonate) followed by
      reductive cleavage with BH4-. Edman degradation of CNBr fragments from band 3
      labeled in intact cells with Woodward's reagent K and [3H]BH4- showed that Glu681
      is heavily labeled under conditions in which Cl- exchange is inhibited, SO4=
      exchange is accelerated, and Cl- conductance is accelerated. No other glutamate
      residue in band 3 is detectably labeled under the conditions of these
      experiments, as demonstrated either by Edman degradation or by the lack of label
      in major known proteolytic fragments. It is concluded that Glu681 is the binding
      site for the H+ that is transported with SO4= during band 3-catalyzed H+/SO4=
      cotransport. This residue is conserved among all species of red cell band 3 (AE1)
      as well as the related proteins AE2 and AE3. Glu681 is the first amino acid
      residue in band 3 which has been identified as a binding site for a transported
      substrate (H+). The functional characteristics of this residue suggest that it
      lies within the transport pathway and can be alternately exposed to the
      intracellular and extracellular media.

PMID- 1352775
TI  - Transcriptional mechanisms of type I collagen gene expression are differentially
      regulated by interleukin-1 beta, tumor necrosis factor alpha, and transforming
      growth factor beta in Ito cells.
AB  - Regulation of the procollagen type I (Pro alpha 1) gene in cultured Ito cells by
      diverse cytokines was studied. Specifically, we have examined the effect of
      interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and
      transforming growth factor beta (TGF beta) on collagen biosynthesis, levels of
      Pro alpha 1 (I) mRNA, and rate of transcription of Pro alpha 1 (I) gene. TGF beta
      stimulated procollagen synthesis at least 2-fold at every concentration tested (5
      20 ng/ml), whereas TNF alpha inhibited it at the same concentrations. In contrast
      to what occurs in dermal fibroblasts, IL-1 beta (5-20 units/ml) preferentially
      inhibited procollagen production as measured by [3H]proline incorporation. A
      similar pattern was obtained when total protein synthesis was analyzed by
      [25S]methionine radiolabeling. Interestingly, while TGF beta-treated cells
      exhibited greater than 3-fold increase in steady-state levels of Pro alpha 1 (I)
      mRNA, the treatment with IL-1 had no effect on procollagen mRNA levels. TNF alpha
      treatment resulted in a 2-fold decrease in the amount of collagen mRNA. The
      treatment with combinations of cytokines indicated that collagen gene expression
      in Ito cells is differentially regulated by these cytokines. Furthermore, nuclear
      run-off transcription experiments were performed. The results obtained suggest
      that TGF beta regulates increasing collagen type I gene expression at
      transcriptional levels, and TNF alpha inhibits the transcriptional rate of Pro
      alpha 1 (I) gene. It is noteworthy that IL-1 beta acts on collagen type I gene
      regulation by a separate mechanism at a posttranscriptional level.

PMID- 1352776
TI  - Characterization of the human lysyl oxidase gene locus.
AB  - Lysyl oxidase (EC 1.4.3.13) is a copper-dependent enzyme acting principally on
      collagen and elastin catalyzing the formation of aldehyde cross-links. It is also
      believed to possess a tumor suppressor activity as the anti-oncogene of ras.
      While rat, human, and mouse lysyl oxidase cDNAs have been cloned, little is known
      about the structure of the gene, its organization, or regulation. This paper
      describes the cloning of an intronic segment of the human lysyl oxidase gene.
      Sequence analysis defined the location of an intron that separates the prepro
      coding segments from the segment encoding the catalytic domain. Genomic
      restriction mapping and gene copy number data established that multiple lysyl
      oxidase mRNA transcripts originate from a single gene and thus are products of
      alternative splicing. Northern analysis of adult and fetal fibroblast RNA showed
      a dominant approximately 4.3-kilobase lysyl oxidase mRNA transcript that varied
      in abundance as a function of cell line. These data are consistent with a complex
      mechanism regulating the expression of the lysyl oxidase gene.

PMID- 1352777
TI  - Alpha 1-adrenoceptor-mediated Ca(2+)-entry from the extracellular fluid and
      Ca(2+)-release from intracellular stores: no role for alpha 1A,B-adrenoceptor
      subtypes in the pithed rat.
AB  - 1. In the present study, we tested the hypothesis that in the pithed rat
      preparation two subtypes of the alpha 1-adrenoceptor are linked to two different
      signal transduction mechanisms, both of which contribute to vasoconstriction, one
      facilitating Ca(2+)-entry from the extracellular fluid (alpha 1A) and one
      promoting the release of Ca2+ from intracellular sources (alpha 1B). 2. The
      selective alpha 1A-adrenoceptor antagonist, 5-methyl-urapidil, and the selective
      alpha 1B-adrenoceptor antagonist, chloroethylclonidine, were unable to
      discriminate between alpha 1-adrenoceptor-mediated pressor responses, which
      relied on an entry of extracellular Ca2+ sensitive to nifedipine and an
      intracellular release of Ca2+ insensitive to nifedipine, respectively. 3.
      Chloroethylclonidine, 12.5 and 25 mg kg-1 i.v., were equieffective, and had only
      minor effects on alpha 1-adrenoceptor-mediated increases in diastolic blood
      pressure. This could be associated with a small decrease in the receptor-reserve
      of the pithed rat preparation due to irreversible receptor blockade by this
      antagonist. These data indicate that chloroethylclonidine-sensitive alpha 1
      adrenoceptors constitute only a minor fraction of the total alpha 1-adrenoceptor
      population on rat arterial resistance vessels. 4. Chloroethylclonidine behaved as
      a partial agonist eliciting a small increase in baseline diastolic blood pressure
      which could be inhibited by Ca(2+)-entry blockade with nifedipine. 5.
      Chloroethylclonidine potentiated the pressor responses elicited by the alpha 2
      adrenoceptor agonists UK-14,304 and azepexole (B-HT 933). 6. No evidence was
      found in the pithed rat that alpha 1-adrenoceptor-mediated Ca(2+)-entry from the
      extracellular fluid and Ca(2+)-release from intracellular stores are mediated by
      alpha 1A and alpha 1B-adrenoceptors, respectively.

PMID- 1352778
TI  - Influence of alpha 1-adrenoceptor blockade and/or 5-HT1A agonism on blood
      pressure and heart rate at rest and during exercise in hypertensive dogs.
AB  - 1. Antihypertensive effects resulting from alpha 1-adrenoceptor blockade and
      stimulation of central nervous 5-HT1A receptors were compared with the effects
      arising from stimulation of 5-HT1A receptors alone during arterial hypertension.
      2. Urapidil and 5-methyl-urapidil were less effective in decreasing arterial
      blood pressure than the lowest dose of the selective 5-HT1A receptor agonist,
      flesinoxan. After the higher dose of urapidil, a certain dampening of
      barareceptor reflex was found which was also seen with flesinoxan. 3. Flesinoxan
      was the only drug which did not reduce the exercise-induced increase in systolic
      arterial blood pressure. 4. Stimulation of 5-HT1A receptors alone, which is
      assumed to occur with flesinoxan, exerted antihypertensive activity only at low
      doses, without inducing reflex tachycardia at rest. 5. Only the combined effects
      of alpha 1-adrenoceptor blockade and 5-HT1A receptor stimulation, as assumed to
      occur with urapidil and 5-methyl-urapidil, lead to both a decrease in arterial
      blood pressure at rest and during exercise.

PMID- 1352779
TI  - Neurotransmitter feedback is not important in modulating the noradrenergic
      component of responses of rat vas deferens to twin pulse electrical field
      stimulation.
AB  - 1. Drug effects on the full time-course of tension responses of the rat vas
      deferens to challenges of twin pulse field stimulation (TPFS) were examined. A
      microprocessor-controlled system was used to regulate stimulus delivery, on-line
      data collection and subsequent data analysis. 2. The second, noradrenergic phase
      of the response to the second stimulus of TPFS was missing when the interpulse
      interval was set at 3 s but was progressively restored as the interpulse interval
      was extended to 120 s. 3. With a 3 s interpulse interval, the missing second
      phase of the response to the second stimulus was not restored by the selective
      alpha 2-adrenoceptor antagonists yohimbine, imiloxan or idazoxan, indicative that
      alpha 2-adrenoceptor-mediated feedback inhibition of noradrenaline release is not
      the predominant mechanism modulating this response component. 4. Incubation with
      the P1-purinoceptor antagonist 8-phenyl-theophylline also failed to restore the
      missing noradrenergic component in the response to the second stimulus of TPFS.
      5. Nevertheless, both responses to TPFS were impaired by the selective alpha 2
      adrenoceptor agonist clonidine and by the P1-purinoceptor agonist 2
      chloroadenosine, indicating the presence of functional presynaptic receptors of
      both types. These agonist-induced inhibitory effects were readily reversed by
      those antagonists which had failed to restore the missing noradrenergic component
      in the second response to TPFS.

PMID- 1352781
TI  - Vimentin expression as a late event in the in vitro differentiation of human
      promonocytic cells.
AB  - The administration of either 12-O-tetradecanoyl phorbol-13-acetate (TPA, 3 x 10(
      8) M), sodium butyrate (SB, 10(-3) M), N6,2'-O-dibutyryladenosine-3':5'-cyclic
      monophosphate (dbcAMP, 10(-3) M), cytosine arabinoside (ara-C, 10(-7) M),
      amsacrine (mAMSA, 10(-7) M) or retinoic acid (RA, 10(-6) M) inhibits the growth
      activity of human promonocytic U-937 cells, by arresting them at G1 or at the
      G1/S border (SB, RA, ara-C), at G2 (mAMSA) or at G1 and G2 (dbcAMP). All these
      agents trigger cell differentiation, as proved by the increased expression of the
      maturation-associated CD11b and CD11c surface antigens, and induce the expression
      of the vimentin gene at both the protein and the mRNA levels. TPA, SB and dbcAMP
      behave as "early" inducers, in the sense that vimentin mRNA levels are rapidly
      increased (hour 6) upon drug administration. In contrast, mAMSA and RA behave as
      "late" inducers, since they do not increase vimentin mRNA levels until 48 to 72
      hours, following the stimulation of surface antigen expression. The action of RA
      is characterized by an initial inhibition period, in which the basal level of
      vimentin mRNA is abolished (hour 24). Nevertheless, this RNA is later re-induced,
      to reach at 72 hours higher levels than in untreated cells. Moreover, RA is
      capable of delaying the early induction of vimentin expression caused by TPA and
      SB, without affecting the normal expression of differentiation markers. Taken
      together, these results strongly suggest that vimentin expression is not required
      at the initial stages of promonocytic cell differentiation, although it could
      play a role at an advanced stage.

PMID- 1352782
TI  - Determination of cabergoline in plasma and urine by high-performance liquid
      chromatography with electrochemical detection.
AB  - A sensitive and selective high-performance liquid chromatographic method for the
      determination of cabergoline in plasma and urine has been developed. After
      buffering plasma and urine samples, cabergoline was extracted with a methylene
      chloride-isooctane mixture, back-extracted into 0.1 M phosphoric acid, then
      analysed by reversed-phase high-performance liquid chromatography. Quantitation
      was achieved by electrochemical detection of the eluate. The linearity, precision
      and accuracy of the method were evaluated. No interference from the biological
      matrices (human plasma and urine) was observed. The assay was still inadequate in
      terms of sensitivity for the quantitation of cabergoline plasma concentrations
      after a single oral dose of 1 mg of the drug to humans, but was successfully used
      in the determination of the urinary excretion of the drug.

PMID- 1352780
TI  - Early disulfide bond formation prevents heterotypic aggregation of membrane
      proteins in a cell-free translation system.
AB  - We previously demonstrated that a heterotypic complex of the two rat
      asialoglycoprotein receptor subunits was assembled during cell-free translation
      (Sawyer, J. T., and D. Doyle. 1990. Proc. Natl. Acad. Sci. USA. 87:4854-4858). We
      have characterized this system further by analyzing polypeptide interactions
      under both reducing and oxidizing translation conditions. This report shows that
      the complex represents a heterogeneous interaction between reduced membrane
      proteins rather than a specific oligomeric structure. In the reduced state
      membrane proteins interact in this system to form aggregates of diverse size and
      composition. The aggregated nascent polypeptides interact with the immunoglobulin
      heavy chain binding protein but this protein is not an integral component of the
      aggregate. Aggregation occurs via the exoplasmic domain, rather than the
      transmembrane domain, and the folding of this domain by the formation of
      intramolecular disulfides, prevents the interaction from occurring. Additionally,
      the folded molecules containing intramolecular disulfides lack high affinity
      binding activity and thus appear to resemble the earliest folding intermediates
      seen in vivo (Olson, J. T., and M. D. Lane. 198. FASEB (Fed. Am. Soc. Exp. Biol.)
      J. 3:1618-1624). These results lead us to suggest that the formation of
      intramolecular disulfides during early biogenesis serves to prevent nonspecific
      associations between nascent polypeptides.

PMID- 1352783
TI  - DNA typing of isolates associated with the 1988 sporotrichosis epidemic.
AB  - DNA typing techniques were used to examine selected clinical and environmental
      isolates of Sporothorix spp. recovered from the 1988 sporotrichosis epidemic in
      multiple states of the United States. Previous studies indicated that isolates in
      one of the six morphologically or physiologically distinct groups (group I)
      obtained from environmental sources were Sporothrix schenckii and were the
      possible etiologic agents responsible for the epidemic. To assess this hypothesis
      at the genetic level, whole-cell DNA was extracted from selected clinical
      isolates and representative members of each of the six environmental groups
      subjected to endonuclease digestion and then analyzed by gel electrophresis. DNA
      types were assigned on the basis of restriction fragment length polymorphism
      patterns. One DNA type was common to clinical and group I isolates but was
      dissimilar from the DNA types exhibited by groups II to VI. In contrast, a
      variety of DNA types were associated with isolates in groups II to VI. The latter
      groups appeared to make up a heterogeneous collection of fungi, with some members
      of the same group having different DNA types but with others from different
      groups possessing identical DNA types. Thus, DNA typing studies confirmed that
      group I environmental isolates are indistinguishable from clinical isolates and
      that group II to VI isolates represent a complex of related fungi with similar
      Sporothrix anamorphs.

PMID- 1352784
TI  - Molecular typing of Staphylococcus aureus on the basis of coagulase gene
      polymorphisms.
AB  - Staphylocoagulase, a major phenotypic determinant of Staphylococcus aureus,
      exists in multiple allelic forms, in part because of the existence of gene
      variants within the 3'-end coding region. This region contains a series of
      repeating 81-bp DNA sequences which differ both in the number of tandem repeats
      and the location of AluI restriction sites among different isolates. Utilizing
      this finding, we developed a novel typing method for S. aureus based on
      polymerase chain reaction amplification of the variable region of the coagulase
      gene followed by AluI restriction enzyme digestion and analysis of restriction
      fragment length polymorphism (RFLP). Among 30 S. aureus isolates studied
      initially, a total of 10 distinct RFLP patterns were observed. There was
      excellent correlation of the RFLP patterns with typing of these isolates by
      multilocus enzyme electrophoresis at 20 chromosomal loci. This coagulase RFLP
      method was used to analyze an additional 39 S. aureus isolates and successfully
      traced the source of an outbreak of methicillin-resistant S. aureus infections at
      a local hospital.

PMID- 1352785
TI  - Insertion element IS1081-associated restriction fragment length polymorphisms in
      Mycobacterium tuberculosis complex species: a reliable tool for recognizing
      Mycobacterium bovis BCG.
AB  - Recently, the insertion element IS1081 from Mycobacterium bovis was identified.
      In this study, the usefulness of IS1081 in the epidemiology of tuberculosis was
      investigated. The host range of this insertion sequence was found to be
      restricted exclusively to the group of Mycobacterium tuberculosis complex
      bacteria, whereas none of the 10 mycobacterial species which do not belong to the
      M. tuberculosis complex contained IS1081-homologous DNA. All 99 M. tuberculosis
      complex strains investigated carried five or six copies of IS1081, and very
      limited IS1081-associated restriction fragment length polymorphisms were observed
      among the strains. Seven different IS1081-containing bands were distinguished in
      each strain, and the patterns differed only in one or two insertion sequence
      containing bands. The banding pattern of M. bovis BCG differed in the presence of
      a 8.0-kb IS1081-containing PvuII fragment which was absent from all other M.
      tuberculosis complex strains.

PMID- 1352786
TI  - Differentiation of slowly growing Mycobacterium species, including Mycobacterium
      tuberculosis, by gene amplification and restriction fragment length polymorphism
      analysis.
AB  - A two-step assay combining a gene amplification step and a restriction fragment
      length polymorphism analysis was developed to differentiate the Mycobacterium
      species that account for greater than 90% of potentially pathogenic isolates and
      greater than 86% of all isolates in clinical laboratories in the United States.
      These species are M. tuberculosis, M. bovis, M. avium, M. intracellulare, M.
      kansasii, and M. gordonae. With lysates of pure cultures as the template, two
      oligonucleotide primers that amplified an approximately 1,380-bp portion of the
      hsp65 gene from all 139 strains of 19 Mycobacterium species tested, but not from
      the 19 non-Mycobacterium species tested, were identified. Digestion of the
      amplicons from 126 strains of the six most commonly isolated Mycobacterium
      species with the restriction enzymes BstNI and XhoI in separate reactions
      generated restriction fragment patterns that were distinctive for each of these
      species, except for those of M. tuberculosis and M. bovis, which were not
      distinguishable. By including size standards in each sample, the restriction
      fragment profiles could be normalized to a fixed distance and the similarities of
      patterns could be calculated by using a computer-aided comparison program. The
      availability of this data base should enable the identification of an unknown
      Mycobacterium strain to the species level by a comparison of the restriction
      fragment pattern of the unknown with the data base of known patterns.

PMID- 1352788
TI  - MRI of pancreatic gastrinomas.
AB  - Pancreatic islet cell tumors are often small and multiple, and preoperative
      diagnosis can be difficult. In a woman with hypergastrinemia, angiography and CT
      each depicted a solitary lesion. Magnetic resonance images, acquired using fat
      suppression, fast spin echo, and contrast material injection, depicted seven
      separate lesions, which were surgically confirmed.

PMID- 1352787
TI  - Use of restriction fragment length polymorphisms resolved by pulsed-field gel
      electrophoresis for subspecies identification of mycobacteria in the
      Mycobacterium avium complex and for isolation of DNA probes.
AB  - Mycobacterial strains from the Mycobacterium avium complex were compared with
      each other and with Mycobacterium phlei isolates by restriction endonuclease
      digestion of chromosomal DNA with SspI and analysis by pulsed-field gel
      electrophoresis. Characteristic profiles were observed for known typed strains,
      and five groups were identified. Primary bovine isolates identified as
      Mycobacterium paratuberculosis by classical methods were shown to fall into both
      the M. paratuberculosis- and M. avium-like groups. M. paratuberculosis 18 was in
      the latter category. Two Mycobacterium intracellulare strains of different
      Schaefer serotypes had different digestion profiles. In addition, this system was
      exploited for the preparation of DNA probes by the isolation, digestion, and
      subcloning of DNA fragments separated by pulsed-field gel electrophoresis. Probe
      JC12 hybridized only to M. avium complex strains, but not to M. phlei, showing
      characteristic hybridization profiles for each of the groups previously
      identified by pulsed-field gel electrophoresis. The approach taken in the study
      lends itself to the comparative analysis of members of the M. avium complex and
      to the isolation and characterization of DNA probes with specificity for these
      mycobacteria.

PMID- 1352789
TI  - The effects of H2-receptor antagonists on exercise refractoriness in asthma.

PMID- 1352790
TI  - Effects of palytoxin on porcine coronary artery rings.
AB  - Palytoxin, in concentrations as low as 100 fM, caused contractions of porcine
      coronary artery rings. Palytoxin concentrations of less than 1 nM caused slowly
      developing contractions which were not maximal even after 2 h. Rings contracted
      by 100 nM palytoxin achieved maximal tension by 10 min and relaxed to 53% of that
      maximum after 2 h. Verapamil (1 microM) reduced the rate of contractions induced
      by 10 nM palytoxin. Exposure of rings to greater than 10 nM palytoxin for 1-2 h
      reduced contractions to potassium 18 h later to 61% of the expected contraction
      and abolished those to palytoxin administered later. Both 10 and 100 nM palytoxin
      depleted potassium from coronary artery rings. Verapamil (10 microM) prevented
      potassium depletion by 10 nM palytoxin, but neither 10 microM verapamil nor 1
      microM nifedipine prevented potassium depletion in rings exposed to 100 nM
      palytoxin. Thus, the contractile action and the potassium depleting action of
      palytoxin on the porcine coronary artery involve mobilization of nifedipine- and
      verapamil-sensitive calcium. Verapamil- and nifedipine-sensitive calcium was not
      required for depletion of potassium by the highest PTX concentration (100 nM),
      however.

PMID- 1352791
TI  - Oral prostaglandin E2 influences the enterochromaffin-like and somatostatin cell
      populations in the oxyntic mucosa of the rat.
AB  - Our aim was to study the effects of long-term oral administration of different
      doses of prostaglandin E2 (PGE2) and of a synthetic analogue on the endocrine
      cells and on selected epithelial cells of the rat oxyntic mucosa. The endocrine
      cells were visualized by immunohistochemical staining and by the Sevier-Munger
      method. Quantification of the mucosal cells was performed at a light-microscopic
      level using stereological methods. The highest dose of 15-R-15
      methylprostaglandin E2 (MePGE2) increased the total volume of enterochromaffin
      like (ECL) cell profiles whereas no changes were observed after treatment with
      PGE2. On the other hand, the total mucosal volume of chromogranin A
      immunoreactive cells was significantly reduced by both doses of natural PGE2. The
      highest dose of PGE2 increased the total volume of somatostatin-immunoreactive
      cells. The serotonin-immunoreactive cells were very few and unaffected by
      treatments. E2 prostaglandins induced hyperplasia and hypertrophy of epithelial
      cells. A selective trophic action on the mucous but not on the parietal cells was
      observed. The area of the parietal cells was increased in rats treated with the
      analogue. The gastric acid content was increased in rats treated with the highest
      doses of E2 prostaglandins. The plasma level of somatostatin was significantly
      increased in rats given MePGE2 and the highest dose of PGE2. The cell population
      of chromogranin A-immunoreactive cells did not reach the levels of the NECL
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352792
TI  - Marine envenomations. Part 2: Invertebrates.
AB  - As more people travel to the oceans for sport diving and other marine-related
      activities, the incidence of marine envenomations has risen. This article is
      designed to give the emergency medicine physician an overview of varying marine
      envenomations, their clinical presentation, and recommended treatment. Part 1 of
      this article dealt with general wound management and vertebrate envenomations.
      Part 2 addresses invertebrate envenomations.

PMID- 1352793
TI  - Improved enzyme immunosorbent assay for mouse prolactin using penicillinase as
      label.
AB  - Enzyme immunosorbent assay (EIA) for mouse prolactin was established by modifying
      a method originally developed for human prolactin by Shrivastav et al. This
      simple, sensitive, rapid, and reproducible assay utilizes penicillinase as the
      labeling enzyme, rabbit anti-mouse prolactin antibody (Ab) and goat anti-rabbit
      Ig Ab as the first and second antibodies. Prolactin reference preparations and
      enzyme-conjugated prolactin were mixed with the first Ab and incubated for 0.5 h
      at 4 degrees C (24-48 h for serum samples). Then, the sample mixture was
      transferred to the wells of microtiter plate coated with the second Ab. After
      being kept at room temperature for 2 h, the plate was washed and filled with
      substrate solution (penicillin V). Absorbance at 620 nm was measured with an
      ELISA reader to quantitate the amount of conjugated prolactin bound to the second
      Ab. The prolactin levels obtained by this assay exhibited good correlation with
      those measured by radioimmunoassay (RIA) (y = 0.95x + 9.14, r = 0.943), and the
      sensitivity of EIA was equivalent to that of RIA (1.7 ng/ml). The CVs of intra
      assay and inter-assay by EIA for mouse serum samples ranged comparably to those
      by RIA.

PMID- 1352794
TI  - Expression and role of integrin receptors in Sezary syndrome.
AB  - The potential role of integrins in the epidermotropism of the atypical
      lymphocytes of Sezary syndrome was studied by monitoring the expression of alpha
      and beta chains and their major ligands in skin biopsies and peripheral blood
      cells in patients at different progression stages. Most mononuclear cell
      integrins were also detected on infiltrating cells including the leukocyte
      complex CD11/CD18, alpha 4 beta 1, and their ligands, ICAM-1 and VCAM-1.
      Conversely, alpha 6 and beta 4 were present only in epidermal basal cells.
      Mononuclear infiltrates of SS were positive for both alpha 3 and alpha 5 chains,
      whereas in inflammatory cutaneous diseases only alpha 5 was expressed, indicating
      that a major feature of Sezary cells is the unique expression of alpha 3 beta 1.
      Significant changes of alpha 3 beta 1 were monitored in the follow-up of Sezary
      patients and correlated with the results of the therapy. The heterodimer alpha 1
      beta 1 was absent from mononuclear cells except in one case. Among matrix
      molecules, laminin and type IV collagen displayed a pattern similar to that of
      the controls, whereas fibronectin and tenascin deposition were apparently
      increased. Circulating Sezary cells, both at diagnosis and during follow-up, were
      alpha 3 and alpha 5 negative and failed to acquire these adhesion molecules after
      mitogenic stimulation. We propose that the expression of alpha 3 beta 1 is a
      distinguishing feature of skin-infiltrating Sezary cells and may be related to
      their epidermotropism. It could also be adopted as an additional parameter of the
      progression and therapeutic stage of Sezary syndrome.

PMID- 1352796
TI  - Simultaneous diagnosis of coagulation factor XIIA (F13A) and plasminogen (PLG)
      phenotypes by polyacrylamide gel isoelectric focusing.
AB  - In this paper, we report a simple rapid method for simultaneous determination of
      Coagulation Factor XIIIA (F13A) and plasminogen (PLG) phenotypes by PAGIF with a
      nominal pH range of 3.5 to 10, followed by immunofixation and silver stain.
      Critical considerations concerning the conditions of molecular separation and
      detection strategies are also presented.

PMID- 1352795
TI  - Aspects of the embryology and neural development of the American lobster.
AB  - It is feasible to study the anatomical, physiological, and biochemical properties
      of identifiable neurons in lobster embryos. To exploit fully the advantages of
      this preparation and to lay the foundation for single-cell studies, our recent
      goals have been to 1) establish a quantitative staging system for embryos, 2)
      document in detail the lobster's embryonic development, 3) determine when
      uniquely identifiable neurons first acquire their transmitter phenotypes, and 4)
      identify particular neurons that may serve developmental functions. Behavioral,
      anatomical, morphometric, and immunocytochemical studies have led to a detailed
      characterization of the growth and maturation of lobster embryos and to the
      adoption of a percent-staging system based upon the eye index of Perkins (Fish.
      Bull., 70:95-99, 1972). It is clear from these studies that the lobster nauplius
      molts at approximately 12% embryonic development (E12%) into a metanauplius,
      which subsequently undergoes a complete molt cycle within the egg. This molt
      cycle climaxes with the emergence of the first-stage larva shortly after
      hatching. Serotonin and proctolin, neurohormones widely distributed in the
      lobster nervous system, appear at different times in development. Serotonin
      immunoreactive neurons begin to appear at approximately E10%, with the adult
      complement being established by E50%. In contrast, proctolin immunoreactive
      neurons appear later and attain their full complement over a protracted period
      including larval and juvenile stages. The development of serotonergic
      deutocerebral neurons and their targets, the olfactory and accessory lobes in the
      brain, are also examined. The olfactory lobes are forming by E10% and have
      acquired their glomerular organization by E50%, whereas the formation of the
      accessory lobes is delayed; the early rudiments of the accessory lobes are seen
      by E50%, and glomeruli do not form until the second larval stage.

PMID- 1352797
TI  - Variations in prion protein and glial fibrillary acidic protein mRNAs in the
      brain of scrapie-infected newborn mouse.
AB  - To begin to understand the molecular basis of cases of Creutzfeldt-Jakob disease
      recently described in young children, the expression of prion protein and glial
      fibrillary acidic protein (GFAP) mRNAs was investigated during the development of
      the brain of scrapie-infected newborn mice. Changes in the time course of
      expression were identified by Northern blot quantification between days 1 and
      172. Although scrapie-infected and control animals showed no detectable changes
      in brain development (first 56 days of life), GFAP mRNAs were found to increase
      significantly as early as day 84. A 10-fold increase in the level of GFAP mRNA
      was observed in brain between day 112 and death (day 172).

PMID- 1352798
TI  - Dynamic observation of dopamine autoreceptor effects in rat striatal slices.
AB  - Fast-scan cyclic voltammetry has been used to measure dopamine (DA) synaptic
      overflow in slices of rat caudate nucleus induced by electrical stimulation with
      one-, two-, and 50-pulse, 10-Hz trains. Synaptic overflow in this preparation is
      shown to be the result of the competing effects of release and cellular uptake.
      Release caused by all pulses was attenuated by the D2 agonist quinpirole (1
      microM). The rapid time response of the measurements (100 ms) allows the
      autoinhibition induced by endogenous, released DA to be resolved in real time.
      The concentration of DA released during the second pulse of a train was 58% of
      that released by the first pulse, an effect that is partially blocked by the
      addition of 2 microM sulpiride, a D2 antagonist, to the perfusion buffer. DA
      release during the first stimulus pulse is unaffected by 2 microM sulpiride,
      suggesting that autoreceptors are not normally occupied in this preparation.
      Release caused by the third pulse was 14% of the first pulse and also could be
      partially enhanced by 2 microM sulpiride. The duration of the inhibition of
      release induced by endogenous DA was estimated by varying the interval between
      one-pulse stimulations until the overflow of DA induced by the second pulse was
      equal to that on the first; a half-time of approximately 17 s was found. The
      addition of picrotoxin (100 microM) and glutamate (10 microM) to the perfusion
      buffer did not affect stimulated release of DA, although the addition of atropine
      (100 microM) attenuated overflow for all the trains tested.

PMID- 1352799
TI  - gamma-Glutamylaminotransferase and transglutaminase in subcellular fractions of
      rat cortex and in cultured astrocytes.
AB  - The subcellular distribution of gamma-glutamylamino-transferase (EC 2.3.2.2) and
      transglutaminase (EC 2.3.2.1) has been investigated in rat brain tissue
      fractionated by a centrifugation and sedimentation technique. Neither of these
      enzymes was enriched in the synaptosomal fraction. Comparing the in vitro grown
      astrocytes with synaptosomes, we find that both of these enzymes may possibly be
      more important in the glial element of the synaptic region. gamma
      Glutamylaminotransferase is most abundant in capillaries, confirming previous
      reports.

PMID- 1352800
TI  - Glutamate and gamma-aminobutyric acid neurotransmitter systems in the acute phase
      of maple syrup urine disease and citrullinemia encephalopathies in newborn
      calves.
AB  - Cerebral cortex tissue was obtained at autopsy from neonatal Poll Hereford calves
      with clinically confirmed maple syrup urine disease (MSUD), neonatal Holstein
      Friesian calves with clinically confirmed citrullinemia, and matched controls.
      From this, synaptosomes were prepared for studies of neurotransmitter amino acid
      uptake and stimulus-induced release, and synaptic plasma membranes were obtained
      for studies of associated postsynaptic receptor binding sites. As well as having
      abnormal brain tissue concentrations of the pathognomic plasma amino acids
      (markedly increased levels of the branched-chain compounds valine, isoleucine,
      and leucine in MSUD; marked elevation of citrulline levels in citrullinemia),
      both groups of diseased animals showed reduced brain tissue concentrations of
      each of the transmitter amino acids glutamate, aspartate, and gamma-aminobutyric
      acid (GABA). Nontransmitter amino acids were generally unaffected in either
      disease. Citrullinemic calves showed a marked increase in brain glutamine
      concentration; in calves with MSUD, the glutamine concentration was raised, but
      to a much lesser extent. The Na(+)-dependent synaptosomal uptake of both
      glutamate and GABA was markedly reduced (to less than 50% of control values in
      both cases) in citrullinemic calves but was unaltered in calves with MSUD.
      Whereas synaptosomes from normal calves showed the expected stimulus-coupled
      release of transmitter amino acids, especially glutamate and aspartate, and no
      response to stimulus of nontransmitter amino acids, there was no increased
      release of transmitter amino acids in response to depolarization in synaptosomes
      from citrullinemic calves.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352801
TI  - Excitatory amino acid-induced phosphoinositide turnover in guinea pig cerebral
      cortical slices: selective enhancement by spermine of the response to DL-1
      aminocyclopentane-trans-1,3-dicarboxylate.
AB  - In the presence of 1 mM spermine, accumulations of 3H labelled inositol
      phosphates elicited by quisqualate (100 microM) and 1-aminocyclopentane-trans-1,3
      dicarboxylate (t-ACPD, 300 microM) were significantly enhanced by 21 and 26%,
      respectively, without a significant alteration in the accumulation elicited by L
      glutamate (10 mM) or DL-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionate (10
      microM). Analysis of concentration-response data indicated that the presence of
      spermine led to an increase in the maximal response to t-ACPD without altering
      the EC50 value. The stimulatory effect of spermine on the accumulation of t-ACPD
      elicited 3H-inositol phosphates was not reversed by ifenprodil or
      diethylenetriamine (putative polyamine site antagonists), by agents that activate
      or inhibit protein kinase C, or by calcium channel blockade, but was abolished in
      the presence of elevated extracellular calcium ion concentration. We conclude
      that spermine enhances the phosphoinositide turnover in guinea pig cerebral
      cortical slices elicited by the "metabotropic" excitatory amino acid receptor.
      The site through which the action of spermine is mediated remains to be defined,
      but it is apparently distinct from that suggested to modulate N-methyl-D
      aspartate receptor activity.

PMID- 1352802
TI  - Abnormalities in amino acid neurotransmitters in discrete brain regions of
      genetically dystonic hamsters.
AB  - The concentrations of 11 amino acids, including the neurotransmitters gamma
      aminobutyric acid, glutamate, aspartate, glycine, and taurine, were determined by
      HPLC in 12 brain regions of genetically dystonic (dtSZ) hamsters and age-matched
      nondystonic controls. Since dystonia in mutant dtSZ hamsters is transient and
      disappears after about 70 days of age, amino acids were determined at the age of
      maximum severity of dystonia (30-40 days) and after disappearance of the disease,
      to examine which neurochemical changes were related to dystonia. In dtSZ hamsters
      with the maximum severity of dystonia, significant changes in concentrations of
      the neurotransmitters gamma-aminobutyric acid, glutamate, aspartate, and taurine
      were found in several regions involved in motor functions, e.g., cerebellum,
      thalamus, and corpus striatum. Most of these changes were not permanent but
      disappeared in parallel with dystonia, implicating a causal relationship between
      altered aminoacidergic neurotransmission and dystonia in mutant dtSZ hamsters.

PMID- 1352803
TI  - Potent inhibition of scrapie-associated PrP accumulation by congo red.
AB  - Transmissible spongiform encephalopathies (prion diseases), Alzheimer's disease,
      and other amyloidoses result in the accumulation of certain abnormally stable
      proteins that are thought by many to play central roles in disease pathogenesis.
      Using scrapie-infected neuroblastoma cells as a model system, we found that Congo
      red, an amyloid-binding dye, potently inhibits the accumulation of the scrapie
      associated, protease-resistant isoform of protein PrP without affecting the
      metabolism of the normal isoform. Growth of the cells with submicromolar
      concentrations of Congo red for 5 days reduced the amount of protease-resistant
      PrP detected in the cultures by greater than 90%. This activity of Congo red
      suggests that it selectively disrupts the conversion of PrP to the protease
      resistant isoform or destabilizes this isoform once it is made. Potential
      therapeutic applications of Congo red are discussed.

PMID- 1352804
TI  - Characterization of descending facilitation and inhibition of spinal nociceptive
      transmission from the nuclei reticularis gigantocellularis and gigantocellularis
      pars alpha in the rat.
AB  - 1. Descending influences produced by focal electrical stimulation in the nuclei
      reticularis gigantocellularis (NGC) and gigantocellularis pars alpha (NGC alpha)
      on spinal nociceptive transmission and the dorsoventral region of spinal white
      matter mediating stimulation-produced modulation were examined in pentobarbital
      sodium-anesthetized, paralyzed rats. Spinal units studied responded to mechanical
      stimuli and noxious heating (50 degrees C) of cutaneous receptive fields confined
      to the glabrous skin of the ipsilateral hind foot. Recording sites were located
      in laminae I-VI of the L3-L5 spinal segments. 2. Electrical stimulation in the
      NGC or NGC alpha produced both facilitation and inhibition of responses of spinal
      units to noxious heating of the skin. At 33 of 57 stimulation sites in the NGC
      and NGC alpha, electrical stimulation produced biphasic effects, facilitating
      responses at lesser intensities (5-25 microA) and inhibiting responses at greater
      intensities (50-100 microA). At 21 other sites in the NGC and NGC alpha,
      electrical stimulation (5-100 microA) only inhibited, and at 3 sites stimulation
      (5-100 microA) only facilitated responses of spinal units to noxious heating of
      the skin. 3. Electrical stimulation in the NGC or NGC alpha contralateral to the
      spinal recording site produced the same magnitude of facilitation/inhibition or
      inhibition of spinal nociceptive transmission as did stimulation in the
      ipsilateral NGC and NGC alpha. 4. The latencies to descending facilitation and
      inhibition of spinal nociceptive transmission from the NGC and NGC alpha were
      estimated by a cumulative sum technique to be 232 and 80 ms, respectively. 5.
      Responses of spinal units to graded heating (42-50 degrees C) of the skin
      exhibited positively accelerating stimulus-response functions (SRF) throughout
      the temperature range tested. Electrical stimulation at lesser, "facilitating"
      intensities produced a parallel, leftward shift of the SRF, whereas stimulation
      at greater, "inhibitory" intensities significantly decreased the slope of the SRF
      without affecting the threshold for response. 6. To determine whether activation
      of cell bodies in the NGC or NGC alpha were capable of replicating the effects of
      electrical stimulation, L-glutamate was microinjected into sites where electrical
      stimulation facilitated at lesser and inhibited at greater intensities the
      responses of spinal units to 50 degrees C heating of the skin. L-Glutamate (5
      nmol) produced a rapid onset, short-lasting and reproducible facilitation of
      nociceptive transmission; glutamate microinjection into the same site at a
      greater dosage (50 nmol) inhibited responses of the same spinal units.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1352805
TI  - APB suppresses synaptic input to retinal horizontal cells in fish: a direct
      action on horizontal cells modulated by intracellular pH.
AB  - 1. Membrane potentials and cone-driven light responses were recorded from the H1
      type horizontal cells in isolated retinas. Membrane potentials and intracellular
      pH were recorded also in enzymatically dissociated solitary horizontal cells. 2.
      In isolated retinas the glutamate analogue 2-amino-4-phosphonobutyrate (APB)
      hyperpolarized horizontal cells and reduced their light responses in a dose
      dependent manner (5-200 microM). 3. The action of APB depended on the formulation
      of the saline; APB was effective in L-15 saline buffered with N-2
      hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) but not in a commonly
      used, nominally CO2-free bicarbonate/Tris-buffered saline. 4. The major factor
      controlling the potency of APB was intracellular pH. APB was ineffective during
      retinal perfusion with NH4Cl-containing or CO2-free bicarbonate saline, both of
      which are known to alkalinize cells. In contrast, APB was effective in salines
      formulated to acidify the retinal neurons. These included both HEPES and Tris
      buffered salines containing a weak acid and bicarbonate/Tris-buffered saline
      gassed with CO2. 5. APB reduced the size of glutamate-evoked depolarizations in
      solitary horizontal cells but had no independent action in the absence of
      glutamate. This reduction of glutamate-induced depolarization was observed in
      salines formulated to block voltage-dependent calcium and potassium currents. 6.
      The magnitude of APB's antagonistic action on solitary horizontal cells increased
      in a dose-dependent manner from 10 to 200 microM. The antagonism was increased by
      intracellular acidification and was reduced or eliminated by alkalinization. 7.
      We conclude that APB can reduce glutamate-evoked and, by inference, the
      photoreceptor neurotransmitter-evoked depolarization of horizontal cells by
      acting directly on the horizontal cells. This effect of APB is modulated by
      intracellular pH.

PMID- 1352806
TI  - Large aspiny cells in the matrix of the rat neostriatum in vitro: physiological
      identification, relation to the compartments and excitatory postsynaptic
      currents.
AB  - 1. Large aspiny neurons (20-60 microns diam) in the neostriatum were studied in
      an in vitro rat slice preparation by whole-cell recording to reveal physiological
      identification from medium-sized spiny projection cells (10-20 microns diam),
      relation to the patch and matrix compartments, and excitatory synaptic inputs.
      Recorded cells were identified by intracellular biocytin staining. Compartmental
      identification was made by calbindinD28K immunohistochemistry in fixed slices. 2.
      Large stained neurons were morphologically heterogeneous and had aspiny or
      sparsely spiny dendrites and dense local axonal branches. They were located in
      the matrix or on the patch-matrix border. Axonal branches of the large aspiny
      cells were preferentially distributed in the matrix and gave off terminal boutons
      there. Some of the secondary dendrites arising from stem dendrites running along
      the border, however, crossed compartment boundaries and made fine branches in a
      patch. 3. Large aspiny cells had less negative resting membrane potentials and
      lower thresholds for spike generation than medium spiny cells. They showed longer
      duration and larger-amplitude afterhyperpolarizations (AHPs) than medium spiny
      cells. During hyperpolarizing current pulses, apparent resistance slowly reduced,
      and a prominent sag was observed in the voltage record, which was absent in
      medium spiny cells. The large aspiny cells showed no spontaneous firing but had a
      tendency to fire repetitive spikes in response to depolarizing current pulses,
      although spike interval tended to increase in later spikes. Spike frequency of
      large aspiny cells increased less with current intensity than that of medium
      spiny cells. 4. Most large aspiny cells were considered to belong to a single
      physiological class, although one large aspiny cells showed shorter-duration AHPs
      than both most other large aspiny cells and medium spiny cells, and little spike
      frequency adaptation. 5. Excitatory postsynaptic currents (EPSCs) of large aspiny
      cells induced by intrastriatal stimulation had two components. An early, linear
      component was blocked by 10 microM 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX),
      a selective antagonist of non-N-methyl-D-aspartate (NMDA) receptors. A later
      component with a nonlinear current-voltage (I-V) relationship was blocked by 50
      microM DL-2-amino-5-phosphonovaleric acid (DL-APV), a selective antagonist of
      NMDA receptors. 6. From these results, four conclusions can be drawn. 1) Most
      large aspiny neostriatal cells in the matrix, although they take heterogeneous
      shapes, belong to one physiological class with long-duration AHPs and a strong
      time-dependent component of anomalous rectification.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1352807
TI  - Effects of opioid and alpha 2-adrenoceptor agonists on the isolated ileum of
      morphine-dependent guinea-pigs during withdrawal and after clonidine treatment.
AB  - The present study was undertaken to investigate the effect of clonidine
      administration to opiate-dependent guinea-pigs after morphine withdrawal on
      subsequent twitch responses of the longitudinal muscle-myenteric plexus
      preparations to electrical field stimulation. The results indicate that
      clonidine, administered immediately after morphine removal, causes tolerance to
      the inhibition exerted by opioid and alpha 2-adrenoceptor agonists on the
      electrically-evoked twitches. Such a finding suggests that the mechanism of
      action of clonidine involves not only its well-known effects on locus coeruleus
      neurons but also that it has specific actions on the myenteric plexus. This work
      shows the existence of interactions between opioid and alpha 2-adrenoceptor on
      the cholinergic neurons present in the isolated ileum.

PMID- 1352808
TI  - Contractile response of human omental arteries to endothelin.
AB  - The effects of endothelin have been studied in isolated arterial segments (0.8-1
      mm in external diam.) of human omental arteries obtained during the course of
      abdominal operations (15 patients, 7 men and 8 women). Paired segments, one
      normal and the other de-endothelized, were mounted for isometric recording of
      tension in organ baths. Endothelin produced concentration-dependent contractions
      with an EC50 value of 5.4 x 10(-9) M. Removal of endothelium did not affect
      significantly endothelin-induced contractions (EC50, 6.7 x 10(-9) M). Removal of
      extracellular calcium or addition of the calcium channel blocker nicardipine (10(
      6) M) diminished but did not abolish responses to endothelin. These results
      indicate that endothelin exerts powerful contractile effects on human isolated
      omental arteries which are independent of the presence of an intact endothelial
      cell layer; this contraction cannot be explained solely by voltage-dependent
      calcium channels.

PMID- 1352810
TI  - Inhibition of dapsone-induced methaemoglobinaemia by cimetidine in the presence
      of trimethoprim in the rat.
AB  - Administration of dapsone in combination with trimethoprim and cimetidine to male
      rats resulted in a marked decrease (P less than 0.05) in measured methaemoglobin
      levels (46.2 +/- 24% Met Hb h) compared with administration of dapsone alone
      (124.5 +/- 24.4% Met Hb h). The elimination half-life of dapsone (814 +/- 351
      min) was more than doubled in the presence of trimethoprim and cimetidine
      compared with control (355 +/- 160 min, P less than 0.05). However, there were no
      significant differences in AUC and clearance when dapsone was administered in
      combination with trimethoprim and cimetidine compared with dapsone alone. Co
      administration of trimethoprim with dapsone in the absence of cimetidine did not
      affect either methaemoglobin formation, AUCs, half-lives, or clearance values of
      dapsone compared with control. There was a threefold increase in the AUC of
      trimethoprim (6296 +/- 2249 micrograms min mL-1) in the presence of dapsone
      compared with trimethoprim alone (2122 +/- 552 micrograms min mL-1). There was
      also a corresponding decrease in the clearance of trimethoprim in the presence of
      dapsone compared with control (19.1 +/- 6.9 vs 60.8 +/- 21.0 mL min-1). However,
      there was no change in the elimination half-life of trimethoprim between the two
      experimental groups (273 +/- 120 vs 292 +/- 54 min). The AUC of trimethoprim
      increased more than threefold in the presence of cimetidine (7100 +/- 1501
      micrograms min mL-1) compared with trimethoprim alone (2122 +/- 552 micrograms
      min mL-1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352809
TI  - Further characterization of the protective effect of 8-cyclopentyl-1,3
      dipropylxanthine on glycerol-induced acute renal failure in the rat.
AB  - In the rat, treatment with the alkylxanthine 8-cyclopentyl-1,3-dipropylxanthine
      (CPX) at a dose of 0.1 mg kg-1 antagonizes adenosine-induced falls in renal blood
      flow and reduces the severity of glycerol-induced acute renal failure. Treatment
      of glycerol-injected rats with 0.03 mg kg-1 of CPX resulted in no significant
      improvements in a range of indices of renal function. However, treatment with 0.1
      or 0.3 mg kg-1 doses of CPX did significantly ameliorate acute renal failure
      although there were no significant differences in the degree of protection of
      renal function afforded by these two doses. In glycerol-injected rats, 0.1 or 0.3
      mg kg-1 CPX administered either as a single dose or repeated doses every 12 h for
      two days did not inhibit renal phosphodiesterase. Thus the beneficial effects of
      CPX can be produced by doses that have no effect on renal phosphodiesterase
      activity whereas 0.1 mg kg-1 of CPX has been shown previously to antagonize the
      actions of adenosine. The findings provide further evidence that the beneficial
      effect of CPX in glycerol-induced acute renal failure is a consequence of
      adenosine antagonism and not phosphodiesterase inhibition.

PMID- 1352811
TI  - Improved transdermal delivery of prostaglandin E1 through hairless mouse skin:
      combined use of carboxymethyl-ethyl-beta-cyclodextrin and penetration enhancers.
AB  - The optimal prescription of transdermal preparations of prostaglandin E1 (PGE1)
      for treatment of peripheral vascular diseases has been investigated. The chemical
      stability of PGE1 in fatty alcohol/propylene glycol (FAPG) ointment was markedly
      improved by carboxymethyl-ethyl-beta-cyclodextrin (CME-beta-CyD). Application of
      a PGE1 ointment containing the penetration enhancer, 1-dodecylazacycloheptane-2
      one (Azone) or 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101), onto the
      skin of hairless mice showed the increase of blood flow in the skin due to the
      vasodilating action of PGE1. In particular, the ointment containing a PGE1-CME
      beta-CyD complex supplemented with HPE-101 showed the most prominent increase of
      the blood flow. Compared with other ointments, this ointment was found to show
      significantly greater transfer of HPE-101 into in-vitro preparations of the skin
      of hairless mice. Transfer of PGE1 into the skin was thought to be facilitated by
      this increased transfer of HPE-101. These results suggest that a combination of
      CME-beta-CyD and HPE-101 is useful for designing PGE1 ointments for topical
      application with good chemical stability and percutaneous permeability.

PMID- 1352812
TI  - Absorption kinetics of cyclosporin in the rat.
AB  - Cyclosporin was administered (6 mg kg-1, i.v.) over 15 min, or (10 mg kg-1) by
      gavage, to two groups of 5 rats. Following i.v. infusion, cyclosporin exhibited
      triphasic behaviour with mean +/- s.e.m. disposition half-lives of 9.0 +/- 1.3
      min, 4.0 +/- 0.5 h and 16.0 +/- 1.7 h. Following oral administration, peak blood
      concentration (Cmax) of 1290 +/- 93 ng mL-1 was reached after 5 h, when
      cyclosporin absorption essentially ceased. The absolute bioavailability (F) of
      cyclosporin was 24.0%. Standard laboratory rat chow consisting of 2% corn oil did
      not appear to alter cyclosporin absorption kinetics.

PMID- 1352813
TI  - Toloxatone pharmacokinetics in the plasma and cerebrospinal fluid of the rabbit.
AB  - The pharmacokinetics of toloxatone (5 and 10 mg kg-1, i.v.) was studied in
      anaesthetized rabbits. There was a biexponential decline in plasma concentration
      with time. No differences were observed in the pharmacokinetic parameters with
      the increase of the dose. The terminal half-life was short (47.4 +/- 2.8 and 41.5
      +/- 4.2 min for 5 and 10 mg kg-1, respectively). The total clearance was 79 +/-
      18 mL min-1 after a dose of 5 mg kg-1 and 106 +/- 40 mL min-1 after a dose of 10
      mg kg-1. The volume of distribution was 5.8 +/- 2.8 (5 mg kg-1) and 5.4 +/- 1.8 L
      (10 mg kg-1). The average percentage of toloxatone bound to plasma protein was
      30% and was not affected by concentrations within the investigated range. In
      cerebrospinal fluid (CSF), the highest concentrations of toloxatone were obtained
      within 15 min after the end of the injection. The CSF level of toloxatone was
      equal to that of plasma unbound toloxatone and declined at a rate similar to
      toloxatone in plasma. These results suggest that the toloxatone passage through
      the blood-brain barrier may be completed by passive diffusion. In addition, the
      unbound plasma concentration would accurately reflect the toloxatone
      concentration in CSF and could be a useful tool for drug monitoring.

PMID- 1352814
TI  - Stomach outline visualization in gastrointestinal transit studies using
      scintigraphy.
AB  - A major disadvantage of gamma scintigraphy in gastrointestinal transit studies is
      the inability to provide adequate delineation of anatomical details. As an aid to
      the important requirement of outlining the stomach to ensure accurate
      quantification of the time at which material empties from this organ, a new
      technique is described, using short half-life 81mKr gas to provide clearer
      identification of the stomach outline and position.

PMID- 1352815
TI  - Contractions induced by phenylephrine and noradrenaline are differently affected
      by endothelium-dependent relaxation in rat aorta.
AB  - In rings of rat aorta precontracted with phenylephrine (10 microM) or
      noradrenaline (10 microM), addition of carbachol (10 microM) produced an
      endothelium-dependent relaxation. However, regardless of the concentration of
      agonist tested, both the intensity and duration of the relaxation were
      significantly less when noradrenaline, rather than phenylephrine, was used as the
      precontracting agent. The different responses observed do not appear to be
      related to destruction of endothelium-derived relaxing factor by autoxidation of
      noradrenaline since neither EDTA (30 microM) nor superoxide dismutase (30 units
      mL-1) improved the relaxation to carbachol. In addition, in endothelium-free
      rings, the noradrenaline (1 microM)-induced contraction was less sensitive than
      the phenylephrine (1 microM)-induced contraction to sodium nitroprusside (0.1
      microM) or to 8-Br-cGMP (300 microM). With phenylephrine-, but not noradrenaline
      , induced contraction, the relaxation triggered by carbachol was significantly
      reduced by pretreatment of the aortic rings with chloroethylclonidine (50
      microM), which inactivates a subpopulation of alpha 1-adrenoceptors. Thus, the
      results confirm that both alkylation sensitive and resistant alpha 1
      adrenoceptors exist in rat aorta and indicate that EDRF may discriminate between
      these two alpha 1-adrenoceptor subtypes which are differently affected by
      phenylephrine and noradrenaline.

PMID- 1352817
TI  - An in-vitro study of chloroquine transport in the rat submaxillary gland.
AB  - The uptake and efflux of chloroquine by the rat submaxillary gland in-vitro were
      studied under various incubation conditions. Variations in the extracellular pH
      significantly affected both the uptake and efflux of the drug. Increasing
      chloroquine concentration significantly decreased the uptake. Uptake was also
      decreased significantly (P less than 0.05) when compared with control conditions
      (pH 7.40, 37.5 degrees C, O2 aeration, 6 x 10(-6) M chloroquine) by the following
      experimental variations: aeration of the incubation medium with N2 instead of O2;
      decrease of bath temperature from 37.5 to 4 degrees C; addition of metabolic
      inhibitors, cyanide (10(-3) M), iodoacetic acid (10(-3) M) and o-nitrophenol (10(
      3) M). Cimetidine (10(-3) M), a known organic cationic inhibitor, had no
      significant effect on chloroquine uptake when compared with control values. These
      results show that the uptake of chloroquine by the rat submaxillary gland in
      vitro is concentration-dependent and this is indicative of possible saturable
      binding sites for the drug in the gland. These results suggest that the transfer
      of chloroquine across the submaxillary gland may be mediated by an active
      transport process. On the other hand, it is possible that the apparent active
      transport process implicated in this study could be a consequence of chloroquine
      ion trapping in the acidic interior of lysosomes.

PMID- 1352816
TI  - Analysis of the effects of adenosine in skinned bovine coronary artery.
AB  - We have investigated the mechanism of adenosine-induced relaxation in relation to
      its effects on intracellular organelles in Triton X-100- and saponin-skinned
      bovine coronary arteries. In intact coronary arteries, high K+ and prostaglandin
      F2 alpha caused sustained contractions, whereas caffeine produced transient
      contractions. Triton X-100 treatment abolished these contractions. However,
      Triton X-100-skinned coronary arteries were responsive to added free calcium.
      There was no significant difference between calcium concentration-response curves
      obtained in the absence and presence of adenosine (50 microM). Unlike Triton X
      100, in saponin-skinned arteries, caffeine produced transient contractions but
      high K+ and prostaglandin F2 alpha did not. Adenosine had no effect on caffeine
      induced contractions in saponin-skinned coronary arteries. These data suggest
      that adenosine had no direct inhibitory effect on either the contractile
      apparatus or calcium release from sarcoplasmic reticulum in coronary arteries.

PMID- 1352818
TI  - Influence of inhibition of extraneuronal uptake and of O-methylation on the
      hyperglycaemia caused by sympathomimetic amines in depancreatized rats.
AB  - This study aimed at testing whether the O-methylating system (extraneuronal
      uptake + O-methylation) modulates, in-vivo, beta-adrenoceptor-mediated responses.
      The influences of U-0521 (3,4-dihydroxymethylpropiophenone, an inhibitor of
      catechol-O-methyl transferase (COMT)) and hydrocortisone (an inhibitor of
      extraneuronal uptake) on the hyperglycaemia evoked by isoprenaline and adrenaline
      were compared. Both inhibitors enhanced the increase of the plasma glucose level
      induced by either isoprenaline (0.36 nmol kg-1 min-1) or adrenaline (0.55 nmol kg
      1 min-1). The enhancement caused by U-0521 developed faster than that caused by
      hydrocortisone, but was of the same magnitude. This is the first report of
      supersensitivity to sympathomimetic amines caused by inhibition of either COMT or
      extraneuronal uptake in-vivo and for a response not involving smooth muscle
      cells.

PMID- 1352819
TI  - Supersensitivity of isolated atria from diabetic rats to adenosine and
      methacholine: modulation by pertussis toxin.
AB  - The chronotropic response of isolated right atria obtained from rats made
      diabetic 14-15 weeks previously by streptozotocin, was compared with age-matched
      controls. Diabetic rat atria are significantly more sensitive to the negative
      chronotropic actions of adenosine and of methacholine. Pretreating both control
      and diabetic rats with 2.5 mg kg-1 pertussis toxin attenuated the negative
      chronotropic effects of methacholine and adenosine on isolated atria, although
      diabetic atria still displayed a significantly greater sensitivity to these
      agonists (P less than 0.05-0.001). The negative chronotropic effects of
      methacholine and adenosine on both control and diabetic atria were abolished
      following pretreatment with higher doses of pertussis toxin (10 mg kg-1). These
      results suggest that pertussis toxin-sensitive G proteins may be involved in the
      supersensitivity of diabetic hearts to methacholine and adenosine.

PMID- 1352820
TI  - Inhibitory effect of 2-hydroxypropyl-beta-cyclodextrin on crystal-growth of
      nifedipine during storage: superior dissolution and oral bioavailability compared
      with polyvinylpyrrolidone K-30.
AB  - To prevent the crystal-growth of nifedipine during storage, 2-hydroxypropyl-beta
      cyclodextrin (HP-beta-CyD) was employed as a hydrophilic drug carrier and
      compared with polyvinylpyrrolidone K-30 (PVP). Amorphous nifedipine powders were
      prepared by spray-drying with HP-beta-CyD or PVP, and their crystal-growing
      behaviour at accelerated storage conditions were examined by X-ray diffraction
      analysis and microscopy. Although PVP initially retarded the crystallization of
      nifedipine, it failed to control the increase of crystal size after prolonged
      storage at 60 degrees C, 75% r.h., resulting in a remarkable decrease in
      dissolution rate in water. In sharp contrast, a relatively fine and uniform size
      of nifedipine crystals was maintained in the HP-beta-CyD system even after
      accelerated storage conditions. The enhanced dissolution observed for all the HP
      beta-CyD systems in a dissolution medium containing 0.1% non-ionic surfactant HCO
      60 were clearly reflected in the in-vivo absorption of nifedipine following oral
      administration to dogs. These results suggest that HP-beta-CyD is particularly
      useful in solving problems encountered on storage of amorphous nifedipine in
      solid dosage forms.

PMID- 1352821
TI  - Effect of physical and chemical properties on drug release from selected
      thermosoftening vehicles.
AB  - The release profile of several drugs, (chlorpheniramine maleate, salicylic acid,
      hydrochlorothiazide, p-hydroxy benzoic acid, sulphafurazole, anhydrous
      theophylline) and the marker (D&C yellow No. 10) was detailed to determine the
      effect of physical and chemical properties on release from selected
      thermosoftening matrices (Gelucire 50/02 and 50/13). At a concentration of drug
      or marker of 2.5% w/w, hydrochlorothiazide showed the slowest release from
      G50/02, due to its low aqueous solubility, while theophylline showed the highest
      release owing to its low mol. wt and moderate aqueous solubility. Release
      reflected two of the selection criteria, aqueous solubility and mol. wt, set
      forth for the drug/markers used in the study. The hydrophobic matrix, G50/02,
      offered no enhancement in drug release and functioned in a manner commensurate
      with other hydrophobic matrices. No hydrogen bonding was noted between any of the
      drugs or markers and the matrix. As drug or marker concentration increased from
      2.5 to 15% w/w, potential hydrogen bonding was noted between p-hydroxy benzoic
      acid and the matrix. Theophylline no longer had the highest release being
      replaced by chlorpheniramine maleate and D&C yellow No. 10. With Gelucire
      excipient G50/13, chlorpheniramine maleate showed the highest release; it
      dissolved within the matrix at experimental temperature and lowered the matrix
      melting point. The matrix swelled upon exposure to the dissolution medium and it
      was from this swollen layer that release occurred. Sulphafurazole,
      hydrochlorothiazide, salicylic acid and p-hydroxy benzoic acid exerted a similar
      effect to chlorpheniramine maleate on the matrix. No hydrogen bonding was
      observed between the drugs and matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352822
TI  - Effect of chronic nicotine treatment and withdrawal on rat striatal D1 and D2
      dopamine receptors.
AB  - The effects on rat striatal dopamine receptors after chronic nicotine
      administration (3 and 12 mg kg-1 day-1), and after withdrawal from chronic
      nicotine (12 mg kg-1 day-1), were studied. After 21 days of continuous minipump
      infusion, the control (saline) and nicotine-treated rats were killed. The
      nicotine-withdrawal rats were killed on day 28, 7 days after pump removal.
      Radioligand studies were performed to determine D1 ([3H]SCH23390) and D2
      ([3H]spiperone) striatal dopamine receptor affinity (Kd) and maximum binding
      (Bmax). Dopamine inhibition of antagonist binding at 3 concentrations and the
      effect of 0.3 mM GTP on binding affinity were examined. No statistically
      significant differences between control and nicotine treatment or withdrawal
      groups were noted in either D1 or D2 receptor Kd or Bmax. Although nicotine has
      been shown to affect nigrostriatal dopamine release, chronic treatment does not
      appear to alter overall striatal dopaminergic receptor binding parameters.

PMID- 1352823
TI  - Calcium-calmodulin-dependent activation of adenylate cyclase in prostaglandin
      induced electrically-monitored intestinal secretion in the rat.
AB  - The calcium-calmodulin antagonist 5-iodo-C8-W7 inhibited the PGE2-induced
      stimulation of cAMP production by isolated enterocytes from rat small intestine.
      It also reduced the secretory response of intestinal sheets to PGE2, measured as
      a rise in short-circuit current. It did not however, inhibit the electrical
      responses to forskolin and dibutyryl cAMP, nor to acetylcholine, a secretagogue
      whose effect is not mediated by cAMP. It is concluded that the receptor-mediated
      activation of adenylate cyclase and the subsequent secretory response are
      dependent upon calcium-calmodulin.

PMID- 1352824
TI  - Alpha 1-adrenoceptor subtypes in the rat ventricular muscle.
AB  - Scatchard analyses of [3H]prazosin binding in rat ventricular muscle membranes
      showed biphasic curves, which identified alpha 1High- and alpha 1Low-affinity
      sites. The alpha 1High-affinity site was completely inhibited by 1 microM
      phenoxybenzamine. The displacement potencies of alpha 1-adrenergic antagonists
      were characterized by [3H]prazosin binding to alpha 1High- and alpha 1Low
      affinity sites in the absence and presence of 1 microM phenoxybenzamine. The
      affinities of most chemicals for alpha 1Low-affinity sites were significantly
      lower than those for alpha 1High-affinity sites, but WB-4101 (2-(2,6-dimethoxy
      phenoxyethyl)aminomethyl-1,4-benzodioxane), arotinolol, cinanserin, nifedipine,
      and p-aminoclonidine had the same affinities for both alpha 1Low- and alpha 1High
      affinity sites. These results show that two alpha 1-adrenoceptor subtypes, alpha
      1High- and alpha 1Low-affinity, are present in the rat heart, and that there are
      physical variations in alpha 1-adrenoceptor binding sites, based on their
      selectivity to antagonists.

PMID- 1352826
TI  - Lung fibrosis in a patient with polyarteritis nodosa receiving cyclophosphamide
      therapy.

PMID- 1352825
TI  - Polyarteritis nodosa confined to calf muscles.
AB  - Two patients who developed pain and tenderness in their calf muscles, without
      other organ system involvement, are described. A gastrocnemius biopsy disclosed
      necrotizing muscular arteritis. Five other reported cases are reviewed and we
      conclude that there is a limited form of polyarteritis nodosa localized to calf
      muscles, with a differentiated and more benign clinical course, a differential
      diagnosis restricted to local pathological processes and prompt response to
      treatment with corticosteroids alone.

PMID- 1352827
TI  - Combined effect of doxazosin and pindolol on blood pressure control and lipid
      concentrations in patients with essential hypertension selected from general
      practice. Hunter Hypertension Research Group.
AB  - Doxazosin, an alpha-adrenergic antagonist with potentially favourable effects on
      lipid status was evaluated in 25 otherwise healthy general practice patients with
      mild to moderate hypertension. A mean dose of 5.7 mg produced a significant fall
      in lying and standing systolic and diastolic blood pressure over an 11 week
      period as well as an 8% increase in HDL cholesterol and a 7.5% decrease in the
      total cholesterol/HDL cholesterol ratio. Following this, the doxazosin dose was
      halved and pindolol, a beta-blocker with intrinsic sympathomimetic activity, was
      added (mean dose 7.8 mg) to maintain blood pressure control. At the completion of
      11 weeks of combined alpha- and beta-blockade, HDL cholesterol and triglyceride
      levels were found to be unaltered when compared to pretreatment; however there
      was a small but significant fall in total cholesterol. This study demonstrates
      that this combination of alpha- and beta-blocking antihypertensive therapy can
      produce potentially favourable blood lipid changes.

PMID- 1352829
TI  - Clinical, basic researchers find common ground in San Diego.

PMID- 1352828
TI  - Comparison of antihypertensive and lipid actions of terazosin and atenolol in
      essential hypertension.
AB  - Terazosin is a selective alpha 1-adrenoceptor antagonist; its actions on the
      serum lipoprotein profile were compared with those of the cardioselective beta
      adrenoceptor antagonist atenolol in 40 patients with mild to moderate
      hypertension. Atenolol and terazosin were titrated over six weeks until blood
      pressure control (diastolic blood pressure less than 90 mmHg or greater than 10
      mmHg fall in blood pressure) or a maximum dose of atenolol 100 mg or terazosin 10
      mg had been achieved. Patients not controlled were then prescribed additional
      diuretic therapy (cyclopenthiazide 0.5 mg and potassium 1200 mg). At each visit
      blood pressure and adverse events were recorded; plasma lipids were measured at
      baseline, six and 12 weeks. During titration there was a linear decrease in
      systolic (-29 mmHg on atenolol and -24 mmHg on terazosin) and diastolic blood
      pressure (-17 and -12 mmHg) in both groups without subsequent change over the
      next six weeks; atenolol reduced heart rate (-11 bpm) without change on
      terazosin. During the initial six weeks the total cholesterol fell in both
      groups; however, there were significant between-treatment differences in
      triglyceride responses with a fall on terazosin and a rise on atenolol. Comparing
      atenolol and terazosin over the total 12 week study (irrespective of thiazide
      treatment) increased triglyceride levels and reduced cholesterol ratios and HDL
      were demonstrated on atenolol, contrasting with reduced triglyceride levels and
      elevated HDL and cholesterol ratios of terazosin.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1352830
TI  - Synaptosomal plasma membrane transport of excitatory sulphur amino acid
      transmitter candidates: kinetic characterisation and analysis of carrier
      specificity.
AB  - The transport kinetics of the excitatory sulphur-containing amino acid (SAA)
      transmitter candidates, L-cysteine sulphinate (L-CSA), L-cysteate (L-CA), L
      homocysteine sulphinate (L-HCSA), and L-homocysteate (L-HCA), together with their
      plasma membrane carrier specificity, was studied in cerebrocortical synaptosome
      fractions by a sensitive high performance liquid chromatographic assay. A high
      affinity uptake system could be demonstrated for L-CSA (Km = 57 +/- 6 microM;
      Vmax = 1.2 +/- 0.1 nmol/min/mg protein) and L-CA (Km = 23 +/- 3 microM; Vmax =
      3.6 +/- 0.1 nmol/min/mg protein), whereas L-HCSA (Km = 502 +/- 152 microM; Vmax =
      6.1 +/- 1.3 nmol/min/mg protein) and L-HCA (Km = 1550 +/- 169 microM; Vmax = 10.3
      +/- 1.1 nmol/min/mg protein) exhibited much lower affinity as transport
      substrates. In all cases, only a single, saturable Na(+)-dependent component of
      uptake could be identified, co-existing with a non-saturable, Na(+)-independent
      influx component. Plasma membrane carrier specificity of the SAAs was established
      following comparison with other high-affinity neurotransmitter systems. High
      affinity L-CSA and L-CA transport and low-affinity L-HCSA and L-HCA transport
      demonstrate strong positive correlations in inhibition profiles when compared
      against each other or individually against the high-affinity transport of L
      [3H]glutamate, L-[3H]aspartate, or D-[3H]aspartate. Moreover, the transport
      systems for the excitatory SAAs exhibited a negative correlation when compared in
      inhibition profiles with the high affinity transport of both [3H] gamma
      aminobutyric acid (GABA) and [3H]taurine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352833
TI  - [Microalbumin excretion in the group of patients with asymptomatic hematuria].
AB  - Urine albumin was determined in patients with chronic glomerular injuries with
      normal renal function, who had shown positive test of microhematuria but negative
      test of proteinuria at any time of our renal clinic. The subjects were divided
      into 4 groups: (1) IgA nephropathy (IgAN); 13, (2) asymptomatic hematuria (AS);
      18, (3) nephrotic syndrome in complete remission (CR); 21 and (4) age matched
      normal subjects; 44. Urine albumin concentration was measured with
      radioimmunoassay in the ambulatory urine, and, in some cases, in the urine
      obtained after supine position for 30 minutes to demonstrate the effect of
      ambulatory physical movement on albumin excretion. Also urine alanine
      aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) were estimated by
      monitoring the absorbance of products released by the enzyme, as the indices of
      tubular function. The results indicated that urine albumin were 8.4 +/- 7.3 mg/g
      Cr (Mean +/- SD) in normal subjects, and 8.8 +/- 8.9 mg/g Cr in CR (vs. controls:
      N.S.), 18.9 +/- 14.5 mg/g Cr in AS (P = 0.0071), and 22.2 +/- 14.9 mg/g Cr in
      IgAN (P = 0.0063). The albumin excretion had no relation with the grade of
      microhematuria and also with the ambulatory physical movement. Moreover, AAP and
      NAG excretion in each group had shown no significant alterations. These results
      indicate that urine albumin increases in IgAN and AS with normal renal function
      and with microhematuria alone, but not in CR. Urine albumin is probably
      glomerular origin, since no abnormality is found in the tubular functions.

PMID- 1352832
TI  - [Recovery of hematopoiesis after high-dose chemotherapy and peripheral blood stem
      cell autografts in children].
AB  - Hematopoietic recovery kinetics were evaluated in 34 children with therapy
      refractory malignant tumors who underwent a total of 35 peripheral blood stem
      cell autografts (PBSCT) after marrow-ablative chemotherapy without total body
      irradiation. A negative correlation was found between the numbers of colony
      forming units of granulocyte-macrophage (CFU-GM) infused per kilogram of the
      patients' body weight and the time of achieving an absolute granulocyte count
      (AGC) of 0.5 x 10(9)/l or a platelet count of 50 x 10(9)/l (granulocyte: r = 
      0.631, p less than 0.001, platelet: r = -0.590, p less than 0.001). The patients
      were classified into three groups; 14 patients who received less than 1 x 10(5)
      CFU-GM/kg (group A), 7 patients who received 1-3 x 10(5) CFU-GM/kg (group B), and
      14 patients who received greater than or equal to 3 x 10(5) CFU-GM/kg (group C).
      The AGC recovered to 0.5 x 10(9)/l by 21 day in group A, 14 day in group B, and
      10 day in group C. The platelet count recovered to 50 x 10(9)/l 102 in group A,
      23 in group B, and 16 day in group C patients. The final platelet infusion was on
      day 60 in group A, day 12 in group B, and day 12 in group C. Transient decrease
      in the blood cell count developed in all patients 3 to 7 weeks after
      transplantation, and two cases developed reversible ITP. In the remaining
      patients, the recovered hematopoietic function was sustained for 1-48 months
      after transplant action.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352834
TI  - [A clinical study of the long-term therapeutic effects of low-dose erythromycin
      in diffuse panbronchiolitis--with special reference to changes in tumor
      associated carbohydrate antigens in serum].
AB  - We investigated the long-term (3-30 months) therapeutic effects of low-dose (300
      600 mg/day) erythromycin in 26 patients with diffuse panbronchiolitis (DPB).
      Significant improvements of pulmonary functions especially in %VC and PaO2 as
      well as respiratory symptoms were shown. However, erythromycin treatment was not
      associated with a significant change in surface phenotypes on peripheral blood
      lymphocytes (CD4, CD8, CD4/CD8). It is well known that serum levels of tumor
      associated carbohydrate antigens such as SLX (sialylated Lewis X-i) and CA19-9
      (sialylated Lewis(a)) are significantly elevated in patients with DPB. In the
      present study, 68.4% (13/19) of DPB patients showed marked elevation of SLX and
      52.9% (9/17) showed marked elevation of CA19-9 levels in serum. These positive
      ratios were significantly decreased by erythromycin treatment to 31.6% (6/19) in
      SLX and 23.4% (4/17) in CA19-9. The mean values of each marker were also
      significantly decreased after erythromycin administration from 54.9 +/- 26.9 U/ml
      to 39.5 +/- 22.1 U/ml for SLX and from 70.5 +/- 77.4 U/ml to 28.8 +/- 37.4 U/ml
      for CA19-9.

PMID- 1352835
TI  - [Sialyl Lewis X-i (SLX) in the bronchoalveolar lavage fluid from patients with
      lung cancer].
AB  - The measurement of serum SLX is thought to be a useful aid in the diagnosis of
      malignant diseases, particularly adenocarcinoma of the lung. In the present
      investigation, we measured and compared SLX values in BALF from affected and
      normal bronchi, obtained from 83 patients. They consisted of 64 males and 19
      females, with mean age of 60 years, consisting of 8 normal controls, 19 cases of
      benign lung disease, and 56 cases of primary lung cancer. SLX value in BALF from
      normal bronchi was significantly higher in patients with lung cancer than in
      normal controls, but there was no significant difference in SLX value between
      lung cancer and benign lung disease. On the other hand, SLX value from affected
      bronchi was significantly higher in patients with lung cancer than in normal
      controls and patients with benign lung disease. The rate of elevated SLX in BALF
      from affected bronchi was significantly higher in patients with lung cancer than
      in those with benign lung disease. These results suggest that measurement of SLX
      levels in BALF from affected bronchi may be a useful method for differential
      diagnosis of primary lung cancer.

PMID- 1352831
TI  - Inhibition of viral and cellular promoters by human wild-type p53.
AB  - Mutation of the p53 tumor suppressor gene is a recurring event in a variety of
      human cancers. Wild-type p53 may regulate cell proliferation and has recently
      been shown to repress transcription from several cellular promoters. We studied
      the effects of wild-type and mutant human p53 on the human proliferating-cell
      nuclear antigen promoter and on several viral promoters including the simian
      virus 40 early promoter-enhancer, the herpes simplex virus type 1 thymidine
      kinase and UL9 promoters, the human cytomegalovirus major immediate-early
      promoter-enhancer, and the long terminal repeat promoters of Rous sarcoma virus,
      human immunodeficiency virus type 1, and human T-cell lymphotropic virus type I.
      HeLa cells were cotransfected with a wild-type or mutant p53 expression vector
      and plasmids containing a chloramphenicol acetyltransferase reporter gene under
      viral (or cellular) promoter control. Expression of wild-type p53 correlated with
      a consistent and significant (6- to 76-fold) reduction of reporter enzyme
      activity. A mutation at amino acid 143 of p53 releases this inhibition
      significantly with all the promoters studied. Expression of a p53 mutated at any
      one of the five amino acid positions 143, 175, 248, 273, and 281 also correlated
      with a much smaller (one- to sixfold) reduction of reporter enzyme activity from
      the herpes simplex virus type 1 thymidine kinase promoter. These mutant forms of
      p53 are found in various cancer cells. Thus, failure of tumor suppression
      correlates with loss of the promoter inhibitory effect of p53.

PMID- 1352836
TI  - Cardiovascular and renal control of blood pressure. Proceedings of a conference.
      Villeneuve-les-Avignon, France, October 31-November 1, 1991.

PMID- 1352838
TI  - [Withdrawal of neuroleptics--a successful project at a nursing home for the
      mentally retarded].

PMID- 1352837
TI  - Amino acid neurotransmitters in hypertension.
AB  - There is compelling evidence for the participation of excitatory and inhibitory
      amino acids in the neural regulation of blood pressure in the normotensive rat.
      This is most clearly evident in the neural pathways which form the baroreceptor
      reflex arc. Excitatory amino acids are contained in baroreceptor afferents,
      neurons in the nucleus tractus solitarius (NTS) and neurons in the rostral
      ventrolateral medulla (RVLM). Inhibitory neurons in the caudal ventrolateral
      medulla (CVLM) contain gamma-aminobutyric acid. Electrophysiological and
      pharmacological evidence indicates that amino acid neurotransmitters are
      critically important to the normal function of these integrative sites in the
      baroreceptor reflex. Spontaneously hypertensive rats (SHR) differ from Wistar
      Kyoto (WKY) controls in their responses to stimulation, inhibition or lesions of
      neurons in the baroreceptor arc. One week after baroreceptor denervation, blood
      pressure is elevated in WKY but not in SHR. Stimulation of the CVLM results in a
      greater fall in pressure in SHR than WKY, whereas injection of tetrodotoxin into
      the CVLM results in a smaller increase in pressure in SHR. Blockade of glutamate
      receptors in the spinal cord attenuates the response to stimulation of the RVLM
      in both SHR and WKY, but reduces resting blood pressure in SHR only. These
      experiments suggest that altered activity in amino acid pathways contributes to
      the pathogenesis of hypertension in SHR.

PMID- 1352839
TI  - [Severe adverse effect of the anti-allergy drug loratadine--warning against
      prolonged use of non-prescription drugs].

PMID- 1352840
TI  - Clonal analysis of Escherichia coli serotype O6 strains from urinary tract
      infections.
AB  - A total of 36 Escherichia coli urinary tract isolates (UTI) of serotype O6, with
      different combinations of capsule (K) and flagellin (H) antigens, were analysed
      according to the outer membrane pattern (OMP), serum resistance properties,
      mannose-resistant hemagglutination using various types of erythrocytes, and also
      for the genetic presence and the expression of P-fimbriae, S fimbriae/F1C
      fimbriae, Type 1 fimbriae, aerobactin and hemolysin. Twenty selected strains were
      further analysed by pulsed field gel electrophoresis (PFGE), elaborating genomic
      profiles by XbaI cleavage and subsequent Southern hybridization to virulence
      associated DNA probes. It could be shown that O6 UTI isolates represent a highly
      heterogeneous group of strains according to the occurrence and combination of
      these traits. Relatedness on the genetic and the phenotypic level was found for
      some of the strains exhibiting the same O:K:H:F serotype. DNA long-range mapping
      further indicated some interesting features, according to the copy number and the
      genomic linkage of virulence genes.

PMID- 1352841
TI  - DNA sequence polymorphism within hominoid species exceeds the number of
      phylogenetically informative characters for a HOX2 locus.
AB  - Within- and between-species variability was examined in a noncoding 238-bp
      segment of the HOX2 cluster. DNA of 4-26 individuals of four species (Pongo
      pygmaeus, Pan troglodytes, Gorilla gorilla, and Homo sapiens) was PCR amplified
      and electrophoresed in a denaturing gradient gel to screen for variability.
      Coupled amplification and sequencing was used to determine the complete sequence
      for each of the different alleles identified, one each in humans and orangutans,
      two in chimpanzees, and four in gorillas. Maximum-parsimony methods were used to
      construct a gene tree for these sequences. Alleles in all four species cluster
      into groups consisting of only one species (i.e., alleles within a species are
      monophyletic). The number of base-pair differences observed among alleles within
      P. troglodytes and within G. gorilla is larger than the number of base-pair
      substitutions that phylogenetically link Pan with Homo. Given these and other
      published data, it is premature to accept any particular phylogenetic tree that
      relates these three genera through two separate speciation events.

PMID- 1352842
TI  - Mitochondrial DNA reveals formation of nonhybrid frogs by natural matings between
      hemiclonal hybrids.
AB  - The European water frog Rana esculenta (RL), a natural hybrid between R.
      ridibunda (RR) and R. lessonae (LL), reproduces by hybridogenesis: haploid
      gametes usually contain an intact chromosome set of R. ridibunda (R); the
      lessonae nuclear genome (L) is lost from the germ line. Hybridity is restored in
      the next generation, via fertilization by syntopic R. lessonae. Matings between
      two hybrids (RL x RL) usually give inviable R. ridibunda (RR) progeny. The adult
      R. ridibunda subpopulation of Trubeschloo, a gravel pit in northern Switzerland,
      consists only of females. Fragment patterns for mitochondrial DNA (mtDNA) of
      these R. ridibunda were identical with those of syntopic R. esculenta and of
      local populations of R. lessonae; they differed from the patterns in eastern
      European populations of R. lessonae and of R. ridibunda mtDNAs (3.7% and 9.3%
      estimated sequence divergence, respectively). In contrast, mtDNAs of two R.
      ridibunda from an introduced Swiss population with both sexes, although different
      (2.7% divergence) from each other, were typical R. ridibunda rather than R.
      lessonae mtDNAs. These data, together with unisexuality, demonstrate conclusively
      that the all-female R. ridibunda population at Trubeschloo originated from
      matings between two R. esculenta. The formation of independently reproducing R.
      ridibunda populations via such hybrid x hybrid matings is precluded because
      progeny of these matings are unisexual. Recombination in the regenerated fertile
      R. ridibunda females, followed by matings with R. lessonae, nevertheless provides
      a mechanism for meiotic reshuffling of genetic material in ridibunda haplotypes
      that is not typically available in hemiclonal lineages.

PMID- 1352843
TI  - Patterns of alcohol consumption in the Kimberley aboriginal population.
AB  - OBJECTIVE: To estimate patterns of alcohol consumption and alcohol-related
      problems among adult Aborigines in the Kimberley region of Western Australia.
      DESIGN: A community survey of adult Aborigines. PARTICIPANTS: A stratified random
      sample of 516 Aboriginal men and women over the age of 15 years in the Kimberley.
      MAIN OUTCOME MEASURES: Participants' reports of their frequency and quantity of
      alcohol consumption, and their lifetime experience of alcohol-related problems;
      and the laboratory measure gamma-glutamyltranspeptidase. RESULTS: Aborigines in
      the Kimberley were more likely to be non-drinkers than non-Aborigines in the
      Australian population, but the majority of drinkers consumed hazardous amounts of
      alcohol: 85% (95% Cl, 82% to 88%) of drinkers in the population were estimated to
      be drinking above the level defined by the National Health and Medical Research
      Council (NHMRC) as harmful. CONCLUSION: Alcohol abuse among Aborigines in the
      Kimberley is a major public health problem which requires urgent action.

PMID- 1352844
TI  - Drug abuse in general practice.

PMID- 1352845
TI  - The pharmacological relief of pain--contemporary issues.
AB  - OBJECTIVE: To provide a general description of the pharmacological principles of
      pain management particularly the management of severe pain with opioid analgetic
      agents. DATA SOURCES: Literature updating previous reviews by the authors in this
      Journal and the Proceedings of the VIth World Congress on Pain, Adelaide, 1-6
      April 1990. STUDY SELECTION: Studies were selected under the subheadings: opioid
      receptors; endogenous opioids; development of new agents; recognition of the need
      to improve analgesia; pharmacokinetics and pharmacodynamics of opioids; and novel
      drug delivery methods. DATA EXTRACTION: The extracted information was more
      descriptive than quantitative. DATA SYNTHESIS: The pharmacological relief of pain
      involves treatment of patients with drugs characterised by extremely large
      interpatient variability in pharmacokinetics and pharmacodynamics by way of an
      extremely complex interaction with endogenous control mechanisms. It is not
      surprising that management of pain in many patients is less than adequate.
      CONCLUSIONS: Although much vigorous interdisciplinary research is being
      undertaken to develop a scientific basis for understanding pain and analgesia,
      improvements in the clinical management of pain can only occur if practitioners
      recognise the need for individualised methods of pain relief and treat their
      patients accordingly.

PMID- 1352847
TI  - HIV and AIDS.

PMID- 1352846
TI  - Drug-induced pulmonary disease.
AB  - OBJECTIVE: To review some of the types of drug-induced pulmonary disease reported
      in Australia. DATA SOURCES: Reports of pulmonary side effects made to the
      Australian Adverse Drug Reaction Advisory Committee between December 1972 and
      March 1991. Reports of drug-induced pulmonary disease from other countries are
      also reviewed. STUDY SELECTION: Only reports involving large patient numbers are
      included in the review to limit the bias likely from limited patient numbers.
      DATA EXTRACTION: The incidence of adverse responses to a range of commonly used
      drugs from other countries is compared with reports to the Australian Adverse
      Drug Reaction Advisory Committee in the last 19 years. DATA SYNTHESIS: Of adverse
      drug reactions reported in Australia in the last 19 years 7.7% were of a
      pulmonary side effect and 55% of these involved a syndrome of airway dysfunction.
      Bronchospasm and cough were the two most common symptoms of airway dysfunction
      and beta-blocking drugs and radio contrast media were the drug groups most
      commonly reported to cause them. These figures are similar to data reported from
      other countries. Some of the more commonly occurring types of drug-induced
      disease affecting either the airways or the lung interstices are reviewed.
      CONCLUSIONS: Medical practitioners should maintain a high index of clinical
      suspicion that any unexplained pulmonary disease could be caused by a drug. Most
      of these reactions are reversible if the drug is withdrawn in time and if
      additional appropriate measures are taken as required.

PMID- 1352848
TI  - Changing patterns of medical treatment in acute myocardial infarction.
      Observations from the Perth MONICA Project 1984-1990.
AB  - TYPE OF STUDY: Descriptive study of trends in the drug therapy for acute
      myocardial infarction. SETTING: Population-based register of acute coronary
      events compiled for the years 1984 to 1990 in the course of the Perth MONICA
      project. CASES: 5294 cases meeting clinical criteria for acute myocardial
      infarction. RESULTS: Striking changes were seen in the use of aspirin before
      admission to hospital (from 4% to 18%). During the stay in hospital the use of
      beta-blockers increased steadily from 52% to 76%, while the use of aspirin
      increased 3.5-fold from 25% to 88% and the use of streptokinase increased 13.5
      fold from 2.4% to 32.4%. The proportion of patients prescribed beta-blockers on
      discharge from hospital increased from 46% to 65% and that for aspirin rose from
      16% to 83%. There were also major relative increases in the use of lipid-lowering
      agents and declines in the use of antiarrhythmic drugs. CONCLUSION: These trends
      in the pharmacological management of myocardial infarction mirror the emerging
      evidence from clinical trials, although the increases in the use of certain types
      of drugs antedated publication of the results of major randomised studies. The
      changes in therapy would partly explain observed improvements in case fatality
      and may have contributed to the decline in coronary mortality observed in the
      Perth community.

PMID- 1352849
TI  - [A case with Graves' disease whose TBII index was decreased after heart surgery].
AB  - This case report describes a patient with Graves' disease who underwent heart
      surgery and we studied changes in thyroid hormone and antithyroid autoantibodies.
      TBII index of this case, which was high value before surgery, was decreased after
      surgery for two years, and the patient did not need any antithyroid drug. It is
      suggested that these changes may be due to cardio-pulmonary bypass and
      administration of steroids during heart surgery. This case indicates that heart
      surgery may influence the clinical course of Graves' disease.

PMID- 1352850
TI  - [Correlation of proliferating cell nuclear antigen (PCNA) labeling rate and
      malignancy in gastric cancer: preliminary report].

PMID- 1352853
TI  - AIDS in obstetrics.

PMID- 1352854
TI  - Epidemiology of HIV infection in pregnant women.

PMID- 1352855
TI  - Human immunodeficiency virus type-1 and tuberculosis in an urbanized,
      hospitalised community in Johannesburg, South Africa.

PMID- 1352852
TI  - Comparative analysis of the intracellular localization of c-Myc, c-Fos, and
      replicative proteins during cell cycle progression.
AB  - In eukaryotic cells, nucleus-cytoplasm exchanges play an important role in
      genomic regulation. We have analyzed the localization of four nuclear antigens in
      different growth conditions: two replicative proteins, DNA polymerase alpha and
      proliferating cell nuclear antigen (PCNA), and two oncogenic regulatory proteins,
      c-Myc and c-Fos. A kinetic study of subcellular localization of these proteins
      has been done. In cultures in which cells were sparse, these proteins were
      detected in the nucleus. When proliferation was stopped by the high density of
      culture cells or by serum starvation, these proteins left the nucleus for the
      cytoplasm with different kinetics. DNA polymerase alpha is the first protein to
      leave the nucleus, with the PCNA protein, c-Fos, and c-Myc leaving the nucleus
      later. In contrast, during serum stimulation c-Fos and c-Myc relocalize into the
      nucleus before the replicative proteins. We also noticed that in sparse cell
      cultures, 10% of the cells exhibit a perinuclear staining for the DNA polymerase
      alpha, PCNA, and c-Myc proteins but not for c-Fos. This peculiar staining was
      also observed as an initial step to nuclear localization after serum stimulation
      and in vivo in Xenopus embryos when the G1 phase is reintroduced in the embryonic
      cell cycle at the mid-blastula stage. We suggest that such staining could reflect
      specific structures involved in the initiation of the S phase.

PMID- 1352851
TI  - Separation of factors required for cleavage and polyadenylation of yeast pre
      mRNA.
AB  - Cleavage and polyadenylation of yeast precursor RNA require at least four
      functionally distinct factors (cleavage factor I [CF I], CF II, polyadenylation
      factor I [PF I], and poly(A) polymerase [PAP]) obtained from yeast whole cell
      extract. Cleavage of precursor occurs upon combination of the CF I and CF II
      fractions. The cleavage reaction proceeds in the absence of PAP or PF I. The
      cleavage factors exhibit low but detectable activity without exogenous ATP but
      are stimulated when this cofactor is included in the reaction. Cleavage by CF I
      and CF II is dependent on the presence of a (UA)6 sequence upstream of the GAL7
      poly(A) site. The factors will also efficiently cleave precursor with the CYC1
      poly(A) site. This RNA does not contain a UA repeat, and processing at this site
      is thought to be directed by a UAG...UAUGUA-type motif. Specific polyadenylation
      of a precleaved GAL7 RNA requires CF I, PF I, and a crude fraction containing PAP
      activity. The PAP fraction can be replaced by recombinant PAP, indicating that
      this enzyme is the only factor in this fraction needed for the reconstituted
      reaction. The poly(A) addition step is also dependent on the UA repeat. Since CF
      I is the only factor necessary for both cleavage and poly(A) addition, it is
      likely that this fraction contains a component which recognizes processing
      signals located upstream of the poly(A) site. The initial separation of
      processing factors in yeast cells suggests both interesting differences from and
      similarities to the mammalian system.

PMID- 1352856
TI  - Vertebrate development. A tool for transgenesis.

PMID- 1352857
TI  - Protein folding. Cytosolic chaperonin confirmed.

PMID- 1352858
TI  - Targeted misexpression of Hox-4.6 in the avian limb bud causes apparent homeotic
      transformations.
AB  - In the limb bud the 5' members of the Hox-4 gene cluster are expressed in a
      nested set of overlapping domains which are progressively restricted in the
      posterior and distal directions. These domains arise early in limb bud
      development and come to approximate the primordia of the major structural
      elements of the limb along the anterior/posterior axis (Fig. 1). This pattern,
      and the fact that surgical manipulations which lead to mirror image duplications
      along the anterior/posterior axis give rise to mirror image duplications of the
      domains of expression of these genes, have led to the proposal that these
      transcription factors specify positional identity along the anterior/posterior
      axis. Here we test this hypothesis directly using replication-competent
      retroviral vectors to expand the domain of expression of the Hox-4.6 gene
      anteriorly during limb development in vivo. We report that alteration of the
      domain of expression of the Hox-4.6 gene in the developing limb leads to
      reproducible pattern alterations consistent with a posterior homeotic
      transformation.

PMID- 1352859
TI  - A case of nephropathia epidemica associated with panhypopituitarism and nephrotic
      syndrome.

PMID- 1352860
TI  - Repetitive injections of L-glutamic acid, in contrast to those of N-methyl-D,L
      aspartic acid, fail to elicit sustained hypothalamic GnRH release in the
      prepubertal male rhesus monkey (Macaca mulatta).
AB  - The purpose of the present study was to examine whether repetitive intravenous
      injections of L-glutamic acid (Glu), like those of N-methyl-D,L-aspartic acid
      (NMA), are able to elicit a sustained train of gonadotropin releasing hormone
      (GnRH) discharges from the hypothalamus of the prepubertal male monkey. In order
      to utilize pituitary luteinizing hormone (LH) secretion as a bioassay of
      hypothalamic GnRH release, the responsiveness of the gonadotroph of the
      prepubertal animals was enhanced prior to the study with a chronic intermittent
      intravenous infusion of the synthetic decapeptide (0.1 microgram/min for 3 min
      every h). Sequential intravenous injections of Glu (150 mg/kg BW) were
      administered at 3-hour intervals for 6 or 24 h. Although the first injection of
      this acidic amino acid elicited a robust discharge of GnRH, subsequent
      stimulation with Glu resulted in GnRH discharges with progressively decreasing
      magnitudes, and by the 9th injection Glu-induced GnRH release was abolished. Peak
      concentrations of circulating Glu following the 1st and 4th Glu injection were
      indistinguishable (3,959 +/- 437 vs. 4,139 +/- 72 nmol/ml, respectively).
      Interestingly, the failure of repetitive intravenous injections of Glu to sustain
      pulsatile GnRH release was not associated with a loss of responsiveness to NMA
      administration, nor was it accompanied by a corresponding decrement in Glu
      induced growth hormone (GH) discharges. As previously demonstrated, repetitive
      intravenous administration of NMA (2-5 mg/kg BW) every 3 h for 9 h sustained
      pulsatile GnRH secretion without decrement. A similar intermittent infusion of
      kainic acid (KA; 1 mg/kg BW every 3 h for 6 h), however, elicited a GnRH response
      that mimicked that observed in response to intermittent Glu treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1352861
TI  - Transmitter content and afferent connections of estrogen-sensitive progestin
      receptor-containing neurons in the primate hypothalamus.
AB  - Progestin receptor-containing cells in the hypothalamus of the adult female green
      monkey (Cercopithecus aethiops) were examined by double-label immunocytochemical
      methods to determine their anatomical location, neurotransmitter content and
      afferent connections. Animals were ovariectomized and administered either
      estradiol valerate or the oil injection vehicle, and were sacrificed after 10
      days of treatment. Using a monoclonal antibody raised against rabbit uterine
      progestin receptor (PR), the distribution of PR-immunoreactive cells in the
      mediobasal hypothalamus and the effect of estrogen treatment on this distribution
      was determined. PR-immunoreactive cells were found throughout the ventromedial
      nucleus (VMN), in the area between the VMN and fornix, and in the medial portion
      of the infundibular nucleus. Estrogen treatment dramatically increased both the
      number of labeled cells and the intensity of immunoreaction product in these
      regions. In double-immunostained sections, boutons immunoreactive for antigens
      indicative of serotonin, pro-opiomelanocortin derived peptides, GABA,
      catecholamine, neuropeptide Y, substance P, cholecystokinin, and somatostatin
      were demonstrated to establish synaptic contact with the soma of PR
      immunoreactive hypothalamic neurons. In colchicine-pretreated animals, all PR
      containing neurons in the mediobasal hypothalamus were found to contain
      immunoreactivity for glutamic acid decarboxylase, the enzyme required for
      synthesis of GABA. No evidence of colocalization with other antigens, including
      LHRH, was observed. Because LHRH neurons are known to receive a rich GABAergic
      innervation PR-containing GABAergic cells may represent steroid-sensitive sites
      of integration for inputs from other neural systems involved in the control of
      gonadotropin secretion.

PMID- 1352862
TI  - Autoradiographic localization of receptors for glucagon-like peptide-1 (7-36)
      amide in rat brain.
AB  - Glucagon-like peptide-1 (GLP-1) has a sparse but well defined distribution in the
      rat brain where it is co-localized with glucagon-like immunoreactivity due to
      other fragments of the glucagon precursor. We have investigated the localization
      of GLP-1 receptors in rat brain using mono-125I-iodinated GLP-1(7-36) amide, the
      biologically active form of the peptide that occurs in brain, as the tracer for
      binding and autoradiographic studies of tissue sections. Displaceable binding of
      the label was sharply localized to discrete areas, being high in mamillary
      nuclei, the arcuate nucleus, nucleus of the solitary tract and the pretectal
      area, intermediate in the lateral septal nuclei, olfactory bulb, dorsal tegmental
      nuclei and the interpenduncular nucleus, and low in other regions. These results
      indicate areas where GLP-1(7-36) amide may have a role as a neurotransmitter or
      neuromodulator.

PMID- 1352863
TI  - Membrane currents induced by L-homocysteic acid in mouse cultured hippocampal
      neurons.
AB  - The concentration-response relationship of membrane currents induced by L
      homocysteic acid was studied on mouse embryonic hippocampal neurons in culture (n
      = 56). In the majority of neurons two phases in the dose-response relationship
      could be distinguished. The first was characterized by responses to 3-100 microM
      L-homocysteic acid which desensitized with a time-constant greater than 1 s in a
      concentration-dependent manner and were antagonized by 30 microM D-L-2-amino-5
      phosphonovaleric acid indicating activation of the N-methyl-D-aspartate
      receptors. At higher concentrations of L-homocysteic acid this component was
      strongly depressed. The second phase was characterized by sustained responses
      that were concentration-dependent (1 mM L-homocysteic acid maximum concentration
      tested) and were not blocked by D-L-2-amino-5-phosphonovaleric acid indicating
      activation of non-N-methyl-D-aspartate receptors. Eight neurons did not exhibit
      these two-phase characteristics in the concentration-response relationship at the
      beginning of the recording. The magnitude of responses to L-homocysteic acid was
      positively related to concentration and the responses were partially blocked by D
      L-2-amino-5-phosphonovaleric acid. In these neurons, however, repeated
      applications of L-homocysteic acid at concentrations 30 microM up to 300 microM
      resulted in a long-lasting, three- to four-fold increase of the membrane current.
      This increase was completely blocked by D-L-2-amino-5-phosphonovaleric acid (50
      100 microM) suggesting that it was produced by activation of receptors.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1352864
TI  - Effects of 6-hydroxydopamine lesions of the prefrontal cortex on tyrosine
      hydroxylase activity in mesolimbic and nigrostriatal dopamine systems.
AB  - The effects of prefrontal cortical dopamine depletion on subcortical dopamine
      function in the rat were examined. 6-Hydroxydopamine lesions of the dopaminergic
      innervation of the prefrontal cortex did not alter concentrations of dopamine or
      its metabolite 3,4-dihydroxyphenylacetic acid in either the striatum or nucleus
      accumbens. Similarly, the activity of the catecholamine biosynthetic enzyme
      tyrosine hydroxylase in the striatal complex was not changed in animals with
      prefrontal cortical lesions. Animals sustaining neurotoxic lesions of the
      prefrontal cortex were challenged with haloperidol in order to activate
      submaximally tyrosine hydroxylase activity. The magnitude of the haloperidol
      induced increase in enzyme activity in the nucleus accumbens was significantly
      greater in lesioned subjects than in control animals. These data suggest that
      lesions of the prefrontal cortical dopamine innervation do not result in
      significant alterations in basal dopaminergic function in the striatal complex.
      However, lesions of the dopaminergic innervation of the prefrontal cortex
      significantly increase the responsiveness of mesolimbic dopamine afferents to
      pharmacological challenge.

PMID- 1352865
TI  - Host dopaminergic afferents affect the development of DARPP-32 immunoreactivity
      in transplanted embryonic striatal neurons.
AB  - Homotopic transplantation provides an interesting way to observe the
      relationships between developing cells and ingrowing host afferents. We have
      performed a complete and selective elimination of the mesostriatal dopaminergic
      system in adult rats to observe the influence of its absence on the development
      and chemical differentiation of embryonic striatal cells. Cell suspensions from
      striatal primordia of 14-15-day-old embryos were transplanted into host striata
      that were (i) neuron-depleted by kainic acid (control group) or (ii) deprived of
      dopamine by 6-hydroxydopamine prior to the neuronal depletion by kainic acid
      (experimental group). The expression of dopamine- and adenosine 3',5'
      monophosphate-regulated phosphoprotein (DARPP-32) by transplanted cells was
      observed in correlation with their innervation by host dopaminergic afferents
      which in turn were identified by tyrosine hydroxylase immunohistochemistry.
      Observations were made between four days and three months after transplantation.
      Four days after transplantation, no immunoreactivity for DARPP-32 was observed in
      transplants of control animals despite the presence of tyrosine hydroxylase
      immunopositive fibers growing from the host to discrete cell clusters in the
      transplant. DARPP-32-labeled cells appeared soon afterwards. Six days after
      transplantation they displayed varying intensities of immunoreaction, ranging
      from just detectable to normal levels and were specifically targeted by
      developing tyrosine hydroxylase-immunopositive fibers. The number of DARPP-32
      labeled cells increased rapidly and they formed increasingly compact clusters.
      Fourteen days after transplantation and afterwards, all the DARPP-32-labeled
      cells displayed an intensity of immunoreaction and a distribution comparable to
      that observed in long-term transplants. Transplants in the experimental hosts
      displayed the same organization and developmental features as the control
      transplants with the exception of DARPP-32 labeling which was not detected before
      eight days after transplantation. Ten days after transplantation, the
      distribution and intensity of DARPP-32 labeling was similar to that observed at
      six days in the control group. The evolution of DARPP-32 labeling after 10 days
      in the experimental group paralleled that observed six days post-transplantation
      and beyond in the control group. Dopaminergic mesostriatal host afferents are
      able to provide developing cells in grafted striatal tissues with normal
      innervation very rapidly. Despite this rapidity, the innervation does not seem to
      have any trophic influence on the general development of the transplant but does
      affect the onset time of the expression of neurochemical markers that are
      directly related to its synaptic function.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1352866
TI  - A mechanism for glutamate toxicity in the C6 glioma cells involving inhibition of
      cystine uptake leading to glutathione depletion.
AB  - We have demonstrated that addition of L-glutamate in millimolar amounts to a
      culture of C6 glioma cells induced cell death within 24 h. The glutamate-induced
      toxicity in the C6 glioma cells was completely suppressed by adding L-cystine
      (0.4-1.0 mM), while the C6 cells degenerated in L-cystine-deprived culture
      medium. Kinetic studies of [35S]cystine and [3H]glutamate uptake showed that
      cystine competitively inhibited glutamate uptake, and conversely glutamate
      inhibited cystine uptake competitively, suggesting that C6 cells have a
      cystine/glutamate antiporter (system CG or Xc) similar to that already described
      in the periphery. Exogenous cystine (1 mM) stimulated a release of endogenous
      glutamate from C6 cells in a Na(+)-independent Cl(-)-dependent fashion. Thus, the
      antiporter normally transports glutamate out of and cystine into the cells. With
      the glutamate analogues tested, there was a good correlation between cytotoxicity
      and inhibition of cystine uptake. The de novo synthesis of glutathione was
      largely dependent upon the uptake of extracellular cystine. Intracellular levels
      of glutathione were dramatically decreased within 8-10 h by culture in glutamate
      added or cystine-free medium. Vitamin E (100 microM), an antioxidant, rescued the
      death of C6 cells induced by glutamate exposure or by culture in cystine-deprived
      medium, but did not restore the apparent decrease of intracellular glutathione.
      Taken together, the present data strongly indicate that glutamate-induced cell
      death is initially due to inhibition of cystine uptake through the antiporter Xc
      system; such inhibition leads to glutathione depletion exposing the cells to
      oxidative stress. Excess of extracellular glutamate introduced from endogenous or
      exogenous roots might disorder this mechanism, resulting in cell death.

PMID- 1352867
TI  - FAMC Intensive Stuttering Treatment Program: ten years of implementation.
AB  - An intensive stuttering treatment program for military service members is
      described. Over a 10-year period, 117 stutters have been treated in a program in
      which graded airflow, tension/relaxation, electromyographic biofeedback, and a
      modified hierarchical desensitization procedure have been used to obtain and
      maintain normally fluent speech. All patients treated have met the criterion of
      less than 1% stuttered words. Of 57 patients followed for from 3-36 months after
      treatment, 42 (74%) have maintained normally fluent speech.

PMID- 1352868
TI  - [Effects of therapy with bis-hemisuccinate of ursodeoxycholic acid bisodium salt
      in patients with chronic hepatitis].
AB  - It has recently been shown that ursodeoxycholic acid administration improves
      liver function tests in patients with chronic liver diseases. Aim of the present
      study was to evaluate an ursodeoxycholic acid derivative (bis-hemisuccinate
      bisodic salt Ursodamor, Farmaceutici Damor, Napoli) in patients with chronic
      hepatitis. Forty patients (15 M, 25 F) with biopsy proven chronic liver disease
      participated to the study. Patients were randomly allocated to two treatment
      groups. Twenty patients (4 PBC, 11 CAH/CPH, 5 cirrhosis) received the
      ursodeoxycholic acid derivate at the dose of 600 mg/day, while 20 patients (1
      PBC, 11 CAH/CPH, 8 cirrhosis) received a placebo. For both groups the treatment
      period was six months. ALT serum levels were significantly reduced in the treated
      group (from 84 +/- 14 to 62 +/- 14 p less than 0.0005) while no significant
      change was observed in the placebo group. In the treated group but not in the
      placebo group alkaline phosphatases and gamma-GT were also significantly reduced
      (from 268 +/- 56 to 160 +/- 23 p less than 0.0005 and from 79 +/- 21 to 45 +/- 10
      p less than 0.0005). In conclusion, our results suggest that the administration
      of the ursodeoxycholic acid derivate, bis-hemisuccinate, bisodic salt, improves
      liver function tests in patients with chronic liver hepatitis. Similarly to
      ursodeoxycholic acid this new derivate probably interferes with bile acid pool
      composition by replacing the more detergent and probably more toxic endogenous
      bile acid.

PMID- 1352869
TI  - Adenosine inhibits the synaptic potentials in rat septal nucleus neurons mediated
      through pre- and postsynaptic A1-adenosine receptors.
AB  - Intracellular and voltage-clamp recordings were made from neurons in rat brain
      slices containing dorsolateral septal nucleus (DLSN), in vitro. Bath application
      of adenosine (100 microM) produced a hyperpolarization (2-15 mV) in 46% of DLSN
      neurons (AH-neurons); in the remaining 54% neurons (non-AH-neurons), no
      hyperpolarization to adenosine was observed. Adenosine (1-300 microM) depressed
      not only the excitatory postsynaptic potential (EPSP) but also the inhibitory
      postsynaptic potential (IPSP) and the late hyperpolarizing potential (LHP) evoked
      by stimulation of the hippocampal CA3 area or the fimbria/fornix pathway in both
      AH- and non-AH-neurons. In non-AH-neurons, adenosine did not block current
      responses resulting from glutamate, muscimol or baclofen applied directly to DLSN
      neurons. In AH-neurons, adenosine partially depressed the baclofen-induced
      outward current. Adenosine did not block the directly-evoked IPSP (monosynaptic
      IPSP) as well as the glutamate-induced (hyperpolarizing) postsynaptic potential
      (PSP) that is mediated by GABA released from interneurons. These results suggest
      that adenosine does not directly inhibit the release of GABA. The effects of
      adenosine was mimicked by selective A1-receptor agonists and was blocked by
      selective A1-receptor antagonists. Pertussis toxin (PTX) blocked the
      hyperpolarization induced by adenosine or baclofen applied exogenously. Adenosine
      consistently produced presynaptic inhibition of the EPSP even in DLSN neurons
      treated with PTX. We conclude that adenosine inhibits neurotransmission between
      the hippocampus and septum through activation of pre- and postsynaptic A1
      receptors which couple with G-proteins of different PTX-sensitivity or with
      distinct transduction processes at pre- vs. postsynaptic sites.

PMID- 1352870
TI  - Escherichia coli virulence factors and 99mTc-dimercaptosuccinic acid renal scan
      in children with febrile urinary tract infection.
AB  - Correlation of virulence factors of Escherichia coli with renal inflammation
      documented by 99mTc-dimercaptosuccinic acid renal scan was undertaken in 59
      children with febrile urinary tract infections to identify more accurately the
      role of bacterial virulence factors in the development of pyelonephritis. P
      fimbriae were present in 63% of isolates from the positive scan group and 83% of
      those from the negative scan group (P = 0.126). Multivariate regression analysis
      showed no significant role for established E. coli virulence factors in the
      development of pyelonephritis. The pap genome was independently associated with
      negative scan (P less than 0.007) and with the absence of reflux (P = 0.031). E.
      coli pyelonephritogenic clone O16:K1:H6 was isolated from negative scan patients
      and did not produce hemolysin. We conclude that P fimbriae are important in the
      development of febrile urinary tract infection regardless of the level of
      infection. Virulent E. coli clones described in prior Scandinavian urinary tract
      infection studies were not common causes of pyelonephritis in our patient
      population.

PMID- 1352871
TI  - Otitis media in children born to human immunodeficiency virus-infected mothers.
AB  - Acute otitis media (AOM) is thought to occur frequently in children infected with
      human immunodeficiency virus (HIV). We compared experience with AOM of 28 HIV
      infected children with that of 33 children who seroreverted to HIV antibody
      negative status by age 18 months. The mean number of episodes/year of AOM for
      children who seroreverted decreased from 1.33 in the first year of life to 0.13
      in the third year, whereas the mean number of episodes/year in HIV-infected
      children increased from 1.89 to 2.40. By age 3 years, all HIV-infected children
      had experienced 1 or more episodes of AOM, and 80% had experienced 6 or more,
      whereas 75% of children who seroreverted had experienced 1 or more episodes, and
      none had had 6 or more. HIV-infected children with normal T4 lymphocyte counts
      had a mean of 1.18 episodes of AOM in the first year of life compared with 2.35
      episodes in HIV-infected children with decreased counts (P = 0.023). HIV-infected
      children with low counts had a nearly 3-fold increased risk of recurrent AOM (47%
      vs. 18%).

PMID- 1352872
TI  - Effect of a beta-adrenergic agonist on glucose transport and insulin-responsive
      glucose transporters (GLUT4) in brown adipose tissue of control and obese fa/fa
      rats.
AB  - A beta-adrenergic agonist specific for brown adipose tissue, Ro 16-8714, was
      administered to control and obese insulin-resistant fa/fa rats and glucose
      utilisation measured in brown adipose tissue using the euglycaemic
      hyperinsulinaemic clamp combined with the injection of 2-deoxyglucose. Treatment
      with the beta-agonist increased basal and insulin-stimulated glucose utilization
      in both groups, resulting in an increased effect of the hormone in treated
      animals. This effect is specific for brown adipose tissue and is not found in
      other insulin-sensitive tissue. The total number of insulin-responsive glucose
      transporters (GLUT4) measured in crude membrane preparations was similar in the
      two groups when expressed per total tissue. They were, however, decreased in the
      fa/fa group when expressed per milligram of tissue. Acute treatment with the beta
      adrenergic agonist increased the total number of GLUT4 in both groups. The
      agonist also increased the amount of mRNA coding for GLUT4 suggesting an effect
      on the transcription and/or on the stability of GLUT4 mRNA.

PMID- 1352873
TI  - Purification of PCNA as a nucleotide excision repair protein.
AB  - Human cell free extracts carry out nucleotide excision repair in vitro. The
      extract is readily separated into two fractions by chromatography on a DEAE
      column. Neither the low salt (0.1 M KCl) nor the high salt (0.8 M KCl) fractions
      are capable of repair synthesis but the combination of the two restore the repair
      synthesis activity. Using the repair synthesis assay we purified a protein of 37
      kDa from the high salt fraction which upon addition to the low salt fraction
      restores repair synthesis activity. Amino acid sequence analysis, amino acid
      composition and immunoblotting with PCNA antibodies revealed that the 37 kDa
      protein is the proliferating cell nuclear antigen (PCNA) known to stimulate DNA
      Polymerases delta and epsilon. By using an assay which specifically measures the
      excision of thymine dimers we found that PCNA is not required for the actual
      excision reaction per se but increases the extent of excision by enabling the
      excision repair enzyme to turn over catalytically.

PMID- 1352875
TI  - Dual regulation of human syncytial adenylyl cyclase.
AB  - The dual (stimulatory and inhibitory) regulation of adenylyl cyclase was studied
      in syncytiotrophoblast basal membranes prepared from term human placenta.
      Stimulation of adenylyl cyclase activity with GTP, non-hydrolyzable GTP analogs,
      isoproterenol and PGE1 was observed, confirming the presence of an intact
      stimulatory pathway in these membranes. Investigations of the inhibitory pathway
      revealed tight coupling of the G-protein, Gi alpha, to catalytic adenylyl
      cyclase, with high doses of GTP producing 80 per cent inhibition of GTP/forskolin
      stimulated activity. Confirming Gi alpha involvement, pertussis toxin (PTX)
      treatment of basal membranes augmented the responses of adenylyl cyclase to both
      GTP and forskolin. In addition, immunoblotting of basal membrane proteins
      revealed the presence of the G-protein subunits, Gs alpha, Gi alpha, and G
      beta/gamma. The response of adenylyl cyclase was measured to a series of agonists
      known to inhibit adenylyl cyclase in other tissues, however a reproducible
      inhibitory effect was produced only by somatostatin (approximately 80 per cent).
      Treatment of basal membranes with PTX caused a degree of reversal of the
      somatostatin-mediated adenylyl cyclase inhibition. However, the intoxication was
      insufficient to restore GTP/forskolin-stimulated activity.

PMID- 1352874
TI  - Predicting antisense oligonucleotide inhibitory efficacy: a computational
      approach using histograms and thermodynamic indices.
AB  - Antisense oligonucleotides (ASOs) are designed to bind to a specific mRNA and
      selectively suppress its translation. To facilitate selection of optimal ASO
      targets, we have developed three thermodynamic indices to evaluate putative
      structural complexes important in ASO action. These indices are: a secondary
      structure score (Sscore), which estimates the strength of local mRNA secondary
      structures at the ASO target site; a duplex score (Dscore), which estimates the
      delta Gformation for the ASO:mRNA target sequence duplex; and a competition score
      (Cscore), which is the difference between the Dscore and the Sscore. We also
      present two histograms to graphically display these indices from different
      regions of the mRNA. The indices are compared to the inhibition reported in five
      studies of ASO-mediated suppression of gene expression. The Dscore is the most
      consistent predictor of ASO efficacy in four of the five studies (r2 from 0.44 to
      0.99), while the results of the fifth study could not be predicted by any
      thermodynamic or physical index. Thus the Dscores and their histogram may prove
      useful in selection of ASO targets.

PMID- 1352876
TI  - Parental bias of Ki-ras oncogenes detected in lung tumors from mouse hybrids.
AB  - A mouse strain with low lung tumor susceptibility (C3H) and a strain with high
      lung tumor susceptibility (A/J) were reciprocally crossed to produce C3A and AC3
      F1 hybrid mice. Ki-ras oncogenes were detected in spontaneous and chemically
      induced lung tumors obtained from the C3A and AC3 mice. To further explore the
      genetics of the Ki-ras gene in mouse lung tumor susceptibility, the parental
      origin of Ki-ras oncogenes detected in lung tumors from the F1 hybrids was
      determined by a strategy based on a 37-base-pair deletion in the second intron of
      the A/J Ki-ras allele. Ki-ras oncogenes were derived from the A/J parent in 38 of
      40 tumors obtained from C3A mice and 30 of 30 tumors from AC3 mice. The
      observation that the activated oncogene in hybrids originates from the
      susceptible parent suggests that the Ki-ras gene is directly linked to mouse lung
      tumor susceptibility. This finding may have implications for pulmonary
      adenocarcinoma development in humans, since Ki-ras oncogenes are detected in 35%
      of this human tumor type.

PMID- 1352877
TI  - Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a
      monoclonal antibody.
AB  - P-glycoprotein (Pgp), encoded by the MDR1 gene, is an active efflux pump for many
      structurally diverse lipophilic compounds. Cellular expression of Pgp results in
      multidrug resistance (MDR) in vitro and is believed to be a clinically relevant
      mechanism for tumor resistance to chemotherapy. We have developed a mouse
      monoclonal antibody, UIC2, that recognizes an extracellular epitope of human Pgp.
      UIC2 inhibited the efflux of Pgp substrates from MDR cells and significantly
      increased the cytotoxicity of Pgp-transported drugs, under the conditions where
      no effect was detectable with other anti-Pgp antibodies. Potentiation of
      cytotoxicity by UIC2 was observed with all the tested drugs associated with MDR
      (vinblastine, vincristine, colchicine, taxol, doxorubicin, etoposide, actinomycin
      D, puromycin, and gramicidin D) but not with any of the drugs to which MDR cells
      are not cross-resistant (methotrexate, 5-fluorouracil, cis-platinum, G418, and
      gentamicin). The inhibitory effect of UIC2 in vitro was as strong as that of
      verapamil (a widely used Pgp inhibitor) at its highest clinically achievable
      concentrations. Our results suggest that UIC2 or its derivatives provide an
      alternative or supplement to chemical agents for the reversal of MDR in clinical
      cancer.

PMID- 1352878
TI  - Recombinant anti-erbB2 immunotoxins containing Pseudomonas exotoxin.
AB  - Immunotoxins were made using five different murine monoclonal antibodies to the
      human erbB2 gene product and LysPE40, a 40-kDa recombinant form of Pseudomonas
      exotoxin (PE) lacking its cell-binding domain. All five conjugates were
      specifically cytotoxic to cancer cell lines overexpressing erbB2 protein. The
      most active conjugate was e23-LysPE40, generated by chemical crosslinking of anti
      erbB2 monoclonal antibody e23 to LysPE40. In addition, a recombinant immunotoxin,
      e23(Fv)PE40, was constructed that consists of the light-chain variable domain of
      e23 connected through a peptide linker to its heavy-chain variable domain, which
      in turn is fused to PE40. The recombinant protein was made in Escherichia coli,
      purified to near homogeneity, and shown to selectively kill cells expressing the
      erbB2 protooncogene. To improve the cytotoxic activity of e23(Fv)PE40, PE40 was
      replaced with a variant, PE38KDEL, in which the carboxyl end of PE is changed
      from Arg-Glu-Asp-Leu-Lys to Lys-Asp-Glu-Leu and amino acids 365-380 of PE are
      deleted. The e23(Fv)PE38KDEL protein inhibits the growth of tumors formed by the
      human gastric cancer cell line N87 in immunodeficient mice.

PMID- 1352879
TI  - Design and synthesis of a CD4 beta-turn mimetic that inhibits human
      immunodeficiency virus envelope glycoprotein gp120 binding and infection of human
      lymphocytes.
AB  - Poor bioavailability, rapid degradation, antigenicity, and high cost often limit
      the use of proteinaceous pharmaceuticals. One goal of structural biochemistry is
      the reduction of complex molecules to small functional units that are amenable to
      high-resolution structural analysis and rapid modification. The dissection of
      complex proteins into small synthetic conformationally restricted components is
      an important step in the design of low molecular weight nonpeptides that mimic
      the activity of the native protein. We have developed a reverse-turn mimetic
      system to explore peptide and protein structure-function relationships. We now
      report the design and synthesis of a small molecule (M(r) 810, as its
      trifluoroacetate salt), water soluble, proteolytically stable mimetic of residues
      Gln40-Thr45 of the complementarity-determining 2-like region of CD4. This mimetic
      has a low micromolar Kd for human T-lymphotropic virus type IIIB gp120 and
      reduces syncytium formation.

PMID- 1352880
TI  - Nitric oxide stimulates the ADP-ribosylation of a 41-kDa cytosolic protein in
      Dictyostelium discoideum.
AB  - Nitric oxide-releasing compounds were shown to activate an ADP-ribosyltransferase
      activity in the cytosol of Dictyostelium discoideum. The enzyme ADP-ribosylated a
      cytosolic protein of approximately 41 kDa, p41. Neither cGMP nor GTP and its
      analogues affected this ADP-ribosylation. p41 differs from other substrates ADP
      ribosylated by cholera, pertussis, or diphtheria toxins. Treatment of ADP
      ribosylated p41 with snake venom phosphodiesterase released adenosine 5'
      monophosphate, indicating a mono-ADP-ribose-protein linkage. This linkage was
      stable to neutral hydroxylamine but was sensitive to mercury ions and
      iodomethane, suggesting an attachment to a cysteine residue. Treatment of intact
      cells with nitric oxide-releasing compounds appeared to stimulate the ADP
      ribosylation of p41 and this modification was reversible.

PMID- 1352881
TI  - Isolation of a gene encoding a chaperonin-like protein by complementation of
      yeast amino acid transport mutants with human cDNA.
AB  - A human cDNA library in lambda-yes plasmid was used to transform a strain of
      Saccharomyces cerevisiae with defects in histidine biosynthesis (his4-401) and
      histidine permease (hip1-614) and with the general amino acid permease (GAP)
      repressed by excess ammonium. We investigated three plasmids complementing the
      transport defect on a medium with a low concentration of histidine. Inserts in
      these plasmids hybridized with human genomic but not yeast genomic DNA,
      indicating their human origin. mRNA corresponding to the human DNA insert was
      produced by each yeast transformant. Complementation of the histidine transport
      defect was confirmed by direct measurement of histidine uptake, which was
      increased 15- to 65-fold in the transformants as compared with the parental
      strain. Competitive inhibition studies, measurement of citrulline uptake, and
      lack of complementation in gap1- strains indicated that the human cDNA genes code
      for proteins that prevent GAP repression by ammonium. The amino acid sequence
      encoded by one of the cDNA clones is related to T-complex proteins, which
      suggests a "chaperonin"-like function. We suggest that the human chaperonin-like
      protein stabilizes the NPR1 gene product and prevents inactivation of GAP.

PMID- 1352882
TI  - High-efficiency receptor-mediated delivery of small and large (48 kilobase gene
      constructs using the endosome-disruption activity of defective or chemically
      inactivated adenovirus particles.
AB  - One limit to successful receptor-mediated gene delivery is the exit of the
      endocytosed material from the endosome. We demonstrate here the delivery of
      marker genes to tissue culture cells using a modification of the receptor
      mediated gene delivery technique that exploits the endosomolytic activity of
      defective adenovirus particles. In particular, greater than 90% of the
      transfected-cell population is found to express a beta-galactosidase gene, and,
      most importantly, this high level of expression can be obtained with psoralen
      inactivated virus particles. Furthermore, because the delivered gene is not
      carried within the genome of the adenovirus particle, the size constraints are
      relieved, and we can, therefore, show the delivery of a 48-kilobase cosmid DNA
      molecule.

PMID- 1352883
TI  - Oncogenic point mutations in exon 20 of the RB1 gene in families showing
      incomplete penetrance and mild expression of the retinoblastoma phenotype.
AB  - The retinoblastoma-predisposition gene, RB1, segregates as an autosomal dominant
      trait with high (90%) penetrance. Certain families, however, show an unusual low
      penetrance phenotype with many individuals being unaffected, unilaterally
      affected, or with evidence of spontaneously regressed tumors. We have used single
      strand conformation polymorphism analysis and PCR sequencing to study two such
      families. Mutations were found in exon 20 of RB1 in both cases. In one family a C
      ---T transition in codon 661 converts an arginine (CGG) to a tryptophan (TGG)
      codon. In this family, incomplete penetrance and mild phenotypic expression were
      observed in virtually all patients, possibly indicating that single amino acid
      changes may modify protein structure/function such that tumorigenesis is not
      inevitable. In the second family the mutation in codon 675 is a G----T
      transversion that converts a glutamine (GAA) to a stop (TAA) codon. However, this
      mutation also occurs near a potential cryptic splice acceptor site, raising the
      possibility of alternative splicing resulting in a less severely disrupted
      protein.

PMID- 1352884
TI  - Genetic, cytogenetic, and molecular analyses of mutations induced by melphalan
      demonstrate high frequencies of heritable deletions and other rearrangements from
      exposure of postspermatogonial stages of the mouse.
AB  - Specific-locus experiments have previously shown melphalan to be mutagenic in all
      male germ-cell stages tested and particularly so in early spermatids. All but 2
      of 24 specific-locus mutations recovered were tested genetically,
      cytogenetically, and/or molecularly. At least 12 of 15 tested mutations recovered
      from postspermatogonial stages but only 1 of 7 mutations recovered from stem-cell
      or differentiating spermatogonia gave evidence of being deletions or other
      rearrangements. Melphalan-induced mutations, thus, confirm the pattern of
      dependence of mutation structure on germ-cell stage that had been shown earlier
      for other chemicals. Results of the present investigation illustrate the
      capabilities of combined genetic, cytogenetic, and molecular analyses for
      characterizing the nature of specific-locus mutations. Fine-structure molecular
      mapping of long regions surrounding specific loci has been greatly facilitated by
      the availability of genetic reagents (particularly, deletion complexes) generated
      in specific-locus experiments over the course of decades. Reciprocally, this
      mapping permits increasingly detailed characterization of the nature of lesions
      induced by mutagenic exposures of germ cells, adding great powers for qualitative
      analysis of mutations to the specific-locus test. Cytogenetic and genetic
      investigations also provide evidence on lesion type, especially for loci at which
      mutations cannot yet be analyzed molecularly. Melphalan, like chlorambucil, can
      generate many mutations, a high proportion of which are deletions and other
      rearrangements, making this chemical valuable for generating mutations (at any
      locus) amenable to molecular access.

PMID- 1352885
TI  - The LIM family transcription factor Isl-1 requires cAMP response element binding
      protein to promote somatostatin expression in pancreatic islet cells.
AB  - Many eukaryotic genes are regulated by cAMP through a conserved cAMP response
      element (CRE). Here we show that, in the pancreatic islet cell line Tu6, a well
      characterized CRE in the somatostatin gene does not provide cAMP responsiveness
      but functions as an essential element for its basal activity. DNA-binding and
      functional analyses indicate that the cAMP-responsive factor CREB regulates
      somatostatin expression in these cells without requirement for phosphorylation at
      the protein kinase A-regulated Ser-133 phosphorylation site. In addition to the
      CRE site, cell-specific expression of the somatostatin gene requires a second
      promoter element, which binds the recently characterized LIM family protein Isl
      1. Thus, Isl-1 and CREB appear to synergize on the somatostatin promoter to
      stimulate high-level expression in Tu6 cells. The ability of CREB to function in
      a phosphorylation-independent manner suggests a mechanism by which this protein
      can regulate gene transcription.

PMID- 1352886
TI  - Murine Hox-1.11 homeobox gene structure and expression.
AB  - The Hox-1.11 gene encodes a protein 372 amino acid residues long that contains a
      conserved pentapeptide, a homeodomain, and an acidic region. The amino acid
      sequence of the homeodomain of Hox-1.11 is identical to that of Hox-2.8, and the
      N-terminal and C-terminal regions of Hox-1.11 are similar to those of human
      HOX2H, which is the equivalent of murine Hox-2.8. The Hox-1.11 gene was shown to
      reside on murine chromosome 6, which contains the Hox-1 cluster of homeobox
      genes. One species of Hox-1.11 poly(A)+ RNA approximately 1.7 kb long was
      detected in mouse embryos, which is most abundant in 12-day-old embryos and
      progressively decreases during further embryonic development. The most anterior
      expression of Hox-1.11 poly(A)+ RNA in 12- to 14-day-old mouse embryos was shown
      by in situ hybridization to be in the mid and posterior hindbrain. Hox-1.11
      poly(A)+ RNA also is expressed in the VII and VIII cranial ganglia, spinal cord,
      spinal ganglia, larynx, lungs, vertebrae, sternum, and intestine.

PMID- 1352888
TI  - Genetic and developmental factors in the olfactory response of Drosophila
      melanogaster larvae to alcohols.
AB  - Olfactory responses of Drosophila melanogaster larvae to a homologous series of
      primary alcohols (methanol ... decanol) were tested. Alcohols at either extreme
      of the chain lengths studied (methanol, ethanol and decanol) evoked no
      significant responses. Heptanol and nonanol both produced dose-independent
      responses, larvae being attracted to heptanol and repulsed by nonanol. The
      remaining alcohols elicited dose-related attractive responses. Responses to
      hexanol and nonanol decline with increasing larval age. Genetic differences were
      found for the response to heptanol, with larvae from a Japanese strain,
      Katsunuma, being indifferent to this substance. Chromosome exchange revealed that
      a major factor involved in the response to heptanol is located on chromosome II;
      factors on chromosome III quantitatively modulate this response. Three mutant
      strains were isolated following EMS mutagenesis of chromosome III. These three
      strains, IndifferentA, IndifferentB and IndifferentC, show incomplete or total
      anosmia when stimulated with nonanol. Adult flies from these strains show similar
      effects. IndifferenB and C strains are dominant over the Canton-S control strain;
      the IndifferentA strain shows semi-dominance. Results are discussed in the light
      of the ecology of Drosophila larvae and the relation between olfactory stimulus
      and receptor conformation and number.

PMID- 1352889
TI  - Cell-specific contact selects transmitter responses in an identified leech
      neuron.
AB  - Serotonergic Retzius (R) neurons of the leech form a Cl-dependent synapse with
      pressure-sensitive (P) neurons both in vivo and in vitro. However, P cells show
      an extrasynaptic, cationic response to application of 5-hydroxytryptamine (5-HT)
      which is reduced upon contact between the neurons in culture. We have examined
      the cellular specificity of the selection of 5-HT responses in the P cell by
      pairing it in culture with a variety of identified neurons. Non-synaptic sensory
      cells, non-serotonergic pre- and postsynaptic partners and serotonergic neurons
      that do not form chemical synapses with the P cell failed to alter its responses
      to 5-HT. The selective reduction of the extrasynaptic response to 5-HT in the P
      cell therefore appears to be induced specifically by contact with its only known
      serotonergic partner during neuronal recognition leading to synapse formation.

PMID- 1352887
TI  - Detection of mutant Ha-ras genes in chemically initiated mouse skin epidermis
      before the development of benign tumors.
AB  - An activated Ha-ras oncogene has been consistently found in chemically initiated
      benign and malignant mouse skin tumors, and an activated ras oncogene has been
      shown to initiate the process of mouse skin carcinogenesis. However, the exact
      timing of mutational activation of the Ha-ras gene relative to application of the
      chemical carcinogen is not known. A sensitive mutation-specific PCR technique was
      used to experimentally address the timing of Ha-ras gene mutational activation.
      This technique can detect mutant Ha-ras alleles in the presence of a very large
      excess of normal ras alleles. Activated Ha-ras genes with 61st codon A----T
      mutations were found in the epidermis of mice 1 week after topical initiation
      with 7,12-dimethylbenz[a]anthracene or urethane by using this assay. These
      results were confirmed by Xba I restriction fragment length polymorphism analysis
      and direct DNA sequencing. One week after initiation is 1-2 months before the
      appearance of benign papillomas that harbor activated Ha-ras oncogenes when the
      initiated mice are promoted with the tumor promoter phorbol 12-myristate 13
      acetate. Our data support the hypothesis that initiated epidermal cells
      containing an activated Ha-ras gene can remain dormant in the skin until a tumor
      promoter induces regenerative hyperplasia that allows for outgrowth of these
      cells with an activated ras oncogene to give rise to a benign papilloma.

PMID- 1352890
TI  - Genomes of diploblastic organisms contain homeoboxes: sequence of eveC, an even
      skipped homologue from the cnidarian Acropora formosa.
AB  - We report the nucleotide sequence of eveC, a cnidarian eve-class homeobox; this
      is the first homeobox to be identified in any diploblastic organism, and is only
      the second eve-class in an invertebrate. Similarity between the predicted amino
      acid sequence of the eveC homeodomain and its insect and vertebrate equivalents
      was approximately 75-80% but, in the case of eveC, a role in segmentation can be
      ruled out. Our findings thus support the 'co-option' hypothesis: homeoboxes were
      an early feature of metazoan genomes, corresponding to the DNA-binding domains of
      more general transcription factors.

PMID- 1352891
TI  - Abnormalities in structure and function of limb skeletal muscle fibres of
      dystrophic mdx mice.
AB  - In this study we have shown that the skeletal muscle fibres from adult (older
      than 26 weeks) mdx mice have gross structural deformities. We have characterized
      the onset and age dependence of this feature in mdx mice. The three dimensional
      structure of these deformities has been visualized in isolated fibres and the
      orientation of these deformities was determined within the muscle by confocal
      laser scanning microscopy. We have also shown that the occurrence of
      morphologically abnormal fibres is greater in muscles with longer fibres
      (extensor digitorum longus (EDL) and soleus, 6-7.3 mm long), than in muscles with
      shorter fibres (flexor digitorum brevis (FDB), 0.3-0.4 mm long). A population of
      post-degenerative fibres, with both central and peripheral nuclei coexistent
      along the length of the fibre, has also been identified in the muscles studied.
      We showed that a mild protocol of lengthening (eccentric) contractions (the
      muscle was stretched by 12% during a tetanic contraction) caused a major
      reduction in the maximal tetanic force subsequently produced by mdx EDL muscle.
      In contrast, maximal tetanic force production in normal soleus, normal EDL and
      mdx soleus muscles was not altered by this protocol. We suggest that the deformed
      fast glycolytic fibres which are found in adult mdx EDL but not in adult mdx
      soleus muscles are the population of fibres damaged by the lengthening protocol.

PMID- 1352892
TI  - Action potential waveforms reveal simultaneous changes in ICa and IK produced by
      5-HT in rat dorsal raphe neurons.
AB  - Action potentials were recorded from serotonergic dorsal raphe (DR) neurons
      acutely isolated from the adult rat brain. Action potential waveforms were used
      as command potentials for whole-cell patch-clamp studies to investigate the Ca2+
      and K+ currents underlying action potentials and the modulatory effects of 5
      Hydroxytryptamine (5-HT) on them. These data were compared with currents elicited
      by using rectangular voltage steps of the type commonly used in voltage-clamp
      experiments. In the same cell, 5-HT simultaneously augmented K+ currents and
      inhibited Ca2+ currents. Experimental conditions were chosen which allowed us to
      examine the action of 5-HT on K+ and Ca2+ currents simultaneously or in
      isolation; 5-HT produced a larger inhibition of calcium current during an action
      potential waveform compared with that measured by using rectangular steps of
      voltage. A possible explanation for this finding is that the maximal inhibition
      is seen immediately after a voltage jump and then decreases with time. Action
      potentials are, in general, so brief that little time-dependent relief of block
      is observed. Most of the inhibition of Ca2+ current resulted from a direct effect
      on Ca2+ channels rather than a shortening of the action potential. The inhibition
      of Ca2+ current by 5-HT also decreased the Ca(2+)-activated K+ currents. These
      results suggest that 5-HT reduces DR neuron excitability by the simultaneous
      activation of K+ channel currents open at the resting potential and the
      suppression of Ca2+ channel currents.

PMID- 1352893
TI  - Effects of pattern element density upon displacement limits for motion detection
      in random binary luminance patterns.
AB  - The upper motion displacement threshold (Dmax) was determined with two-frame
      motion sequences of random binary luminance patterns, over a range of pattern
      element sizes and densities. Dmax was little affected by density at small element
      sizes (less than 5 arcmin), in agreement with previous reports. However, at
      larger element sizes (greater than 9 arcmin) Dmax increased as element density
      was reduced in the range 50-5%. We explain our findings by a model which takes
      into account spatial-frequency filtering prior to motion detection, and the
      effects of pattern density upon the statistics of random binary patterns. We also
      implicate the dependence of Dmax upon the contrast energy of the elements in
      broadband patterns, and provide a direct demonstration that Dmax is contrast
      limited over a wide range of pattern contrasts (72-2.5%). Previous reports that
      Dmax is independent of density should be modified to take into account the
      complex effects of density upon the statistics of random patterns, and the
      existence of physiological filtering prior to motion detection.

PMID- 1352894
TI  - Potassium channels cloned from neuroblastoma cells display slowly inactivating
      outward currents in Xenopus oocytes.
AB  - Messenger RNAs (mRNAs) specific for NGK1 and NGK2 potassium channels were
      synthesized from complementary DNAs (cDNAs) that had been cloned from mouse
      neuroblastoma x rat glioma hybrid NG108-15 cells. Outward pottasium currents were
      evoked by 5 s depolarizing voltage commands in Xenopus oocytes injected with NGK1
      or NGK2-specific mRNAs. The NGK1 or NGK2 currents showed different activation
      and inactivation kinetics, and different pharmacological sensitivities. The
      threshold potential for activation of the NGK2 current (-14 mV) was more positive
      than that for the NGK1 (-36 mV). The NGK2 current showed faster inactivation
      during a 5 s depolarizing pulse than did the NGK1 current. Inactivation was best
      fit by time constants of 0.37, 1.5 and 19 s for the NGK2 current and 4.4 and 19 s
      for NGK1. Extracellularly applied tetraethylammonium chloride (TEA) was 1000
      times more potent on the NGK2 current than the NGK1 current. Furthermore we
      examined outward current following co-injection of an equal amount of mRNAs for
      NGK1 and NGK2. The timecourse of inactivation differed from either alone or from
      a simple sum of the two individual currents. TEA sensitivity could not be
      explained by summation of the two homomultimeric channels. These findings suggest
      that both NGK1 and NGK2 proteins assemble to form heteromultimeric K+ channels in
      addition to homomultimeric K+ channels. NGK2 channels and the heteromultimeric
      channels may be responsible for the native transient outward current with slow
      inactivation in NG108-15 hybrid cells.

PMID- 1352895
TI  - Second messenger imbalance hypothesis of schizophrenia.
AB  - Based on the results of studies on intracellular signaling in platelets of
      schizophrenics, an imbalance of the second messenger system is proposed:
      Diacylglycerol (DG), which activates protein kinase C (PKC), was increased, while
      adenylate cyclase (AC)-cAMP function was decreased. It is proposed that the
      increased DG/PKC function may entail a decrease in inositol 1,4,5-trisphosphate
      (IP3)/Ca2+ function and lowering of phosphoinositide turnover. If such a
      pathological intracellular signaling takes place in the brain, it may cause a
      distorted balance of protein activation via phosphorylation in neurons, resulting
      in some of the deficits of schizophrenia. Neuroleptics have been reported to
      antagonize the above-mentioned pathological processes of intracellular signaling.
      The imbalance hypothesis of the DG/PKC pathway and AC-cAMP pathway is not
      inconsistent with the dopamine hypothesis of schizophrenia, because dopamine
      receptor stimulation is indirectly related to reduction in IP3/Ca2+ function and
      lowering of phosphoinositide metabolism.

PMID- 1352896
TI  - Increased turnover of platelet phosphatidylinositol in schizophrenia.
AB  - The potential role of receptor-stimulated phosphatidylinositol (PI) hydrolysis in
      a signal transduction mechanism has been increasingly recognized. Earlier studies
      have suggested a defect in alpha-adrenergic receptor function in the platelets of
      schizophrenic patients. Little is known, however, about the mechanisms for PI
      synthesis, breakdown, and regulation in schizophrenia. The present study was
      undertaken to investigate the metabolic turnover of inositol phospholipids and
      inositol phosphates by incorporation of [3H]myoinositol or [32P]orthophosphate
      into resting and activated platelets of normal controls and schizophrenic
      patients with and without neuroleptic treatment. After 5 h incubation at 37
      degrees C, the majority of [3H]myoinositol was incorporated into platelet PI.
      Following thrombin-induced platelet activation, there was rapid formation of 3H
      labeled inositol phosphates (IPs) with inositol monophosphate (IP1) being the
      most abundant product. The thrombin-induced formation of platelet IPs was found
      significantly higher in both haloperidol-stabilized and drug-free schizophrenics
      than in normal control subjects. When platelets were prelabeled with
      [32P]orthophosphates, thrombin-induced formation of phosphatidic acid (PA) was
      also significantly higher in haloperidol-stabilized schizophrenics than in normal
      controls. It is thought that thrombin-induced platelet activation is mediated
      through hydrolysis of polyphosphoinositides (poly-PI). The present data thus may
      reflect an increased signal transduction in schizophrenia, which is mediated
      through neuroleptic-regulated inositol phospholipid hydrolysis.

PMID- 1352897
TI  - Inositol phospholipid turnover in platelets of schizophrenic patients.
AB  - Abnormalities in blood cell membrane phospholipid composition and metabolism from
      schizophrenic patients have been reported by many groups of investigators. Among
      membrane phospholipids, inositol phospholipids are of special importance as they
      are involved in transduction system that generates second messengers such as
      inositol trisphosphate and diacylglycerol. Our studies on platelet inositol
      phospholipid turnover suggest a significant increase in platelet
      phosphatidylinositol 4,5-bisphosphate levels, an increased production of inositol
      trisphosphate in neuroleptic-treated and neuroleptic-free schizophrenic patients
      platelets and a reduced calcium release by thrombin in neuroleptic-treated
      schizophrenic patients platelets. The enhanced production of inositol
      trisphosphate may be due to an increase in its precursor phosphatidylinositol 4,5
      bisphosphate with an associated desensitisation of the intracellular inositol
      trisphosphate receptor by neuroleptics, which may explain the diminished calcium
      response to thrombin in schizophrenic patients platelets.

PMID- 1352898
TI  - Administration of AP5, a glutamate antagonist, unmasks glycine analgesic actions
      in the rat.
AB  - The effect of intrathecal (IT) injection of glycine alone or in combination with
      2-amino-5-phosphonopentanoate (AP5) on two nociceptive tests--the vocalization
      threshold to tail-shock (VTTS) and the tail-flick latency (TFL)--was studied in
      ovariectomized Sprague-Dawley rats. IT injection of 400 micrograms glycine
      induced a nonsignificant decrease, that is, in comparison with saline, in both
      nociceptive thresholds. IT AP5 (10 micrograms) provoked a slight but significant
      increase in both nociceptive thresholds within the first 15 min postinjection.
      Combination of both glycine (400 micrograms) and AP5 (10 micrograms) produced
      marked and prolonged analgesia in both tests, which was significantly different
      from that obtained with AP5 alone. The results suggest that IT glycine acting
      through the strychnine-sensitive Gly1 receptor produces analgesia provided its
      effect on the Gly2 receptor linked to the NMDA receptor is prevented by an
      antagonist.

PMID- 1352899
TI  - Reproducibility of time structure in motor activity of rats under nocturnal
      conditions.
AB  - Computer pattern recognition systems for the study of spontaneous rat behavior
      have introduced a new analytical technique, the K functions, that expands the
      definition of experimentally induced changes in behavior. Such studies normally
      evaluate three measures, a measure of the number of initiations of specific
      behavioral acts, a measure of the total time of each act, and a measure of
      behavioral time structure, the K functions. Such measures have been shown to be
      very stable and reproducible among control rats observed under normal light
      conditions. This study examines the stability of results from these three
      measures as applied to nine different groups of control Sprague-Dawley male rats
      observed under red light during their normal nocturnal hours. All three measures
      provided stable and reproducible results, but the measure of time structure, the
      K function analysis, provided the greatest consistency, producing values that
      vary by only a few percent.

PMID- 1352900
TI  - Differential effects of dopamine D2 agonist quinpirole upon the dorsal immobility
      response in rats.
AB  - The effects of various dose levels of systemically injected quinpirole upon the
      dorsal immobility response (DIR) over a time course was investigated in male
      rats. A low dose of quinpirole (0.01 mg/kg) significantly attenuated the duration
      of the DIR following the 10-min interval, whereas the highest dose (1.0 mg/kg)
      had a biphasic effect so that at the 10-min interval the duration of the DIR was
      significantly potentiated and at the 60-min interval the duration of the DIR was
      significantly attenuated. The intermediate dose (0.1 mg/kg) had intermediate
      behavioral effects. The data support the growing evidence that quinpirole has
      differential effects upon behavior over time as a function of the dose levels.
      The present data were discussed in reference to presynaptic and postsynaptic
      dopamine D2 receptor theory.

PMID- 1352901
TI  - Rapid and simultaneous assay of monoamine neurotransmitters and their metabolites
      in discrete brain areas of mice by HPLC with coulometric detection.
AB  - For simultaneous assay of the three monoamine neurotransmitters, norepinephrine,
      dopamine, and serotonin, and four respective metabolites in brain tissue, a rapid
      and simple method using high-performance liquid chromatography with coulometric
      detection is described. Because the present method permits the determination of
      these target substrates within 10 min or less in one chromatographic run, 150
      samples can be analyzed using an autosampler and an integrator in a 24-h period.
      Within-run coefficients of variation for the target substrates in the standard
      solution and the whole brain sample were less than 3% and 2% (n = 40),
      respectively. The quantitative detection limits were 0.01-0.1 pmol. The present
      procedure was applied to measure the target substrates in several discrete brain
      areas in mice.

PMID- 1352903
TI  - L-deprenyl in treating negative symptoms of schizophrenia.

PMID- 1352904
TI  - 9th International Symposium on Gastrointestinal Hormones. Leuven, Belgium, 1-5
      September 1992. Abstracts.

PMID- 1352902
TI  - Symptomatology and electrodermal activity as predictors of neuroleptic response
      in young male schizophrenic inpatients.
AB  - This study examined whether the response to treatment with neuroleptic medication
      in 21 schizophrenic patients could be predicted from symptomatology,
      electrodermal activity, and premorbid adjustment. Positive symptoms and high
      levels of electrodermal activity were associated with a good response to
      conventional neuroleptic drugs. However, multivariate analysis indicated that
      symptomatology was the only independent predictor of treatment response.

PMID- 1352905
TI  - Clonal deletion and anergy: from models to reality. 42nd forum in immunology.

PMID- 1352906
TI  - [Current perspectives in bone marrow transplantation].
AB  - Peripheral blood and umbilical cord blood are promising sources of hemopoietic
      stem cells for autologous as well as allogeneic transplantation. The nature of
      the progenitors responsible for early marrow reconstitution after transplantation
      on one hand and for permanent reconstitution on the other hand is getting more
      precise. Features of the cells responsible for GVHD and of those responsible for
      GVL effect (graft versus leukemia effect) will soon allow a distinct monitoring
      of these two activities. Molecular biology will soon permit genetic labelling of
      the graft and thereby bring more precision for its follow-up and modulation in
      vivo in the post-graft period. Correction of an autologous transplant by
      introduction of the adequate gene in the hematopoietic stem cells in case of
      genetic anomaly at this level, should in the future, as suggested by animal
      studies, allow permanent correction of genetic disorders in patients autografted
      according to such a procedure. Finally, introduction of procedure like antisense
      nucleotides against DNA regions responsible for the malignant proliferation of
      tumoral cell, could extend the therapeutic possibilities of autograft.

PMID- 1352907
TI  - [Diagnostic and therapeutic strategy in Zollinger-Ellison syndrome].

PMID- 1352908
TI  - Gastroprotective and antisecretory effects of ebrotidine.
AB  - This study was designed to assess the gastroprotective and secretory effects of
      ebrotidine, a novel H2-receptor antagonist, in humans. Two groups (A and B) of
      male subjects with normal gastric mucosa were used. Group A (six subjects) was
      treated for 3 days with either ebrotidine or placebo in a randomized, crossover
      study, and on the 4th day 100 ml of 50% ethanol was sprayed on the mucosa via an
      endoscope. Pretreatment with ebrotidine significantly reduced the endoscopic
      score of mucosal damage and deep hemorrhagic lesions caused by ethanol as
      compared with those in placebo-treated subjects. In group B (six subjects) the 24
      h pH-metry was assessed with an intraluminal pH electrode placed in the gastric
      corpus and connected to portable recording apparatus. A single oral dose of
      ebrotidine (800 mg) caused a significant reduction in circadian acidity and
      resulted in a marked and significant inhibition of acid secretion for about 6 h
      on administration. We conclude that ebrotidine is highly effective as a
      gastroprotective agent, and as an H2-receptor antagonist shows a potent
      inhibitory effect on gastric acid secretion in humans.

PMID- 1352909
TI  - Somatostatin cells in the oxyntic mucosa of hypo- or hypergastrinemic rats.
AB  - The present report describes the long-term effects of antrectomy, antrum
      exclusion, portacaval shunt, omeprazole treatment, or the combination of
      omeprazole treatment and portacaval shunt on the number and density of
      somatostatin cells in the oxyntic mucosa of the rat. Antrectomy, which is
      associated with hypogastrinemia, raised the number and density of the
      somatostatin cells, whereas antrum exclusion and omeprazole treatment, which are
      associated with hypergastrinemia, reduced the number and density of the
      somatostatin cells. Portacaval shunt, which is associated with hypogastrinemia,
      increased both the number and the density. Omeprazole treatment of portacaval-
      shunted rats suppressed or even reversed the somatostatin cell hyperplasia after
      portacaval shunt alone. From these findings it is unlikely that gastrin
      stimulates the proliferation of somatostatin cells in the oxyntic mucosa. In
      fact, there seems to be an inverse relationship between the serum gastrin
      concentration and the somatostatin cell number.

PMID- 1352910
TI  - [Current technics in endodontics and traumatology. Interview by Kurt Venner].

PMID- 1352911
TI  - Programmed death of T cells in HIV-1 infection.
AB  - In human immunodeficiency virus (HIV) infection, functional defects and deletion
      of antigen-reactive T cells are more frequent than can be explained by direct
      viral infection. On culturing, both CD4+ and CD8+ T cells from asymptomatic HIV
      infected individuals died as a result of programmed cell death (apoptosis).
      Apoptosis was enhanced by activation with CD3 antibodies. Programmed cell death,
      associated with impaired T cell reactivity, may thus be responsible for the
      deletion of reactive T cells that contributes to HIV-induced immunodeficiency.

PMID- 1352912
TI  - Restoration of viral immunity in immunodeficient humans by the adoptive transfer
      of T cell clones.
AB  - The adoptive transfer of antigen-specific T cells to establish immunity is an
      effective therapy for viral infections and tumors in animal models. The
      application of this approach to human disease would require the isolation and in
      vitro expansion of human antigen-specific T cells and evidence that such T cells
      persist and function in vivo after transfer. Cytomegalovirus-specific CD8+
      cytotoxic T cell (CTL) clones could be isolated from bone marrow donors,
      propagated in vitro, and adoptively transferred to immunodeficient bone marrow
      transplant recipients. No toxicity developed and the clones provided persistent
      reconstitution of CD8+ cytomegalovirus-specific CTL responses.

PMID- 1352914
TI  - A light-microscopic immunocytochemical study of the endocrine pancreas in the
      Australian fat-tailed dunnart (Sminthopsis crassicaudata).
AB  - The endocrine pancreas of the Australian fat-tailed dunnart (Sminthopsis
      crassicaudata) was investigated by means of immunocytochemistry using the avidin
      biotin-peroxidase technique. This was a light microscopic study using this
      established technique and has not been previously investigated. Serial paraffin
      sections were stained individually with primary antibodies for anti-porcine
      glucagon, anti-beef pork insulin, anti-human somatostatin, and anti-avian
      pancreatic polypeptide (APP), anti-bovine pancreatic polypeptide (BPP), anti
      serotonin, anti-porcine motilin, showing the same islet. Cells immunoreactive to
      porcine glucagon, porcine insulin, human somatostatin, APP, BPP were found in
      endocrine islets, but BPP and APP also appear to be scattered amidst the exocrine
      portion. Immunoreactive cells were not observed with serotonin and anti-porcine
      motilin. All controls were negative. These results in the dunnart pancreas has
      shown four types of pancreatic endocrine cells. It has also shown that the
      structure of PP may more closely resemble BPP than APP. This study can be related
      to studies in echidnas (Tachyglossus aculeatus) and Australian possum
      (Trichosurus vulpecula). This is a part of an immunocytochemical study
      investigating the endocrine pancreas in Australian mammals.

PMID- 1352913
TI  - Dendritic cells exposed to human immunodeficiency virus type-1 transmit a
      vigorous cytopathic infection to CD4+ T cells.
AB  - The paucity of virus-laden CD4+ cells in individuals infected with human
      immunodeficiency virus type-1 (HIV-1) contrasts with the greatly reduced numbers
      and function of these lymphocytes. A pathway is described whereby dendritic cells
      carry HIV-1 to uninfected T cells, amplifying the cytopathic effects of small
      amounts of virus. After exposure to HIV-1, dendritic cells continue to present
      superantigens and antigens, forming clusters with T cells that are driven to
      replicate. Infection of the dendritic cells cannot be detected, but the clustered
      T cells form syncytia, release virions, and die. Carriage of HIV-1 by dendritic
      cells may facilitate the lysis and loss of antigen specific CD4+ T cells in
      acquired immunodeficiency syndrome.

PMID- 1352915
TI  - Mucocutaneous abnormalities predicted by lymphocyte counts in patients infected
      with the human immunodeficiency virus.
AB  - Abnormalities of the skin are frequent and troubling problems for patients
      infected with the human immunodeficiency virus (HIV). A number of studies have
      assessed the frequency and severity of diseases of the skin and mucous membranes
      reported from other centers, but relationships between dermatologic signs and
      symptoms and either the lymphocyte count or the helper T-lymphocyte count have
      been infrequently noted. In a prospective study of 6 months' duration, one of us
      (A.F.) examined and questioned 61 HIV-seropositive patients at our infectious
      disease clinic. We found a significant association between the number and
      severity of cutaneous abnormalities and the helper T-cell (CD4) count. A trend
      toward significance was also shown between advanced HIV-disease status or
      decreased CD4 counts and pruritus. Our findings suggest that both the peripheral
      blood lymphocyte count and the helper T-cell count are predictive of the
      frequency, severity, and symptoms of skin diseases.

PMID- 1352916
TI  - [Vascular complications in reconstructive surgery of the foot].
AB  - Even when we assess accurately the preoperative vascular damage of the blood
      vessel we intend to use for reconstruction, difficulties may arise during
      operation which cannot be resolved by routine methods. Microvascular surgery is
      an important part of many modern reconstruction procedures which can be used
      during reconstruction of the extremity. As an example the authors describe
      injuries of the left foot involving loos in a 41-year-old patient who was knocked
      down by a taxi. The defect denuded the bone and loss of soft tissues of the heel
      called for free transfer of a vascularized flap. During operation venous
      thrombosis and subsequently arterial thrombosis developed. The use of an
      interposed vein helped to ensure a sufficient blood supply to the transferred
      tissue. The left foot healed well.

PMID- 1352917
TI  - [Deaths caused by antidepressive agents and neuroleptics].

PMID- 1352918
TI  - Use of internal mammary artery in radiation-induced coronary artery disease.
AB  - In 3 patients who had been subjected to mediastinal irradiation for breast
      cancer, the internal mammary artery was used as a conduit for myocardial
      revascularization. Intraoperatively, in all patients the internal mammary artery
      exhibited excellent blood flow and except for mild adhesions between the
      pericardium and epicardium no unusual technical problems were encountered.
      Preoperative assessment of the internal mammary artery by angiography is
      recommended in patients with radiation-induced coronary artery disease who are
      scheduled to undergo myocardial revascularization with intended use of the
      internal mammary artery.

PMID- 1352919
TI  - Blockade of N-methyl-D-aspartate receptors prevents cyanide-induced neuronal
      injury in primary hippocampal cultures.
AB  - Cyanide-induced alterations of cytosolic calcium levels and cytotoxicity were
      examined in primary cultures of rat hippocampus. Cytosolic free Ca2+ ([Ca2+]i)
      levels were measured in hippocampal neurons using the fluorescent probe, fura 2.
      A concentration-dependent rise in [Ca2+]i occurred rapidly following exposure of
      cells to 0.5-10 mM NaCN. In normal medium (1.3 mM Ca2+), 2 mM NaCN produced an
      increase in [Ca2+]i (172 +/- 27% of control), 45 sec following exposure. Ca2+
      elevation produced by NaCN was blocked by removal of Ca2+ from the external
      medium or by pretreatment with the N-methyl-D-aspartate (NMDA) receptor
      antagonist, 2-amino-5-phosphonovalerate (APV). The cytotoxicity of cyanide,
      assessed by measuring the efflux of lactate dehydrogenase, was blocked by APV.
      These results indicate that in hippocampal neurons, cytosolic Ca2+ accumulation
      induced by cyanide originates from the extracellular compartment and the NMDA
      receptor ionophore is a significant route for Ca2+ entry. It is proposed that
      excitotoxic mechanisms may contribute to altered neuronal homeostasis and injury
      associated with cyanide.

PMID- 1352920
TI  - The effects of liver denervation on the regulation of hepatic biliary secretion.
AB  - Effects of liver denervation on bile formation were studied in eight dogs
      prepared with chronic biliary fistulas. The animals were studied in the basal
      state, after feeding, and during infusion of glucagon 50 ng/kg/min, secretin 2
      U/kg/hr, or somatostatin 200 ng/kg/min. After this first set of experiments the
      animals underwent a total hepatic denervation that consisted of section of the
      hepatic ligaments and a careful dissection of the portal vein, hepatic artery,
      and common duct with stripping of all the surrounding connective tissue and
      topical application of phenol. The above experiments were then repeated.
      Denervation did not modify bile flow, or bile salts, cholesterol, or phospholipid
      concentration or output. Biliary response to glucagon and secretin was similar
      before and after denervation. Somatostatin had an anticholerectic effect in both
      intact and denervated animals, but significantly reduced bile salt output only in
      the intact dogs. Feeding had a choleretic effect pre- and postdenervation, and
      the infusion of somatostatin following feeding decreased bile flow to the same
      degree before and after denervation. In the intact animals the output of all
      three biliary lipids was reduced by somatostatin after feeding but they were
      unaffected by somatostatin after denervation. Moreover, cholesterol and
      phospholipid outputs were stable after feeding in intact animals, but
      significantly decreased after denervation. 14C-erythritol clearance studies
      indicated no change in the canalicular component of bile flow with denervation,
      except again during somatostatin suppression of feeding. These data indicate that
      basal bile flow is normal after denervation but that innervation may play an
      important role in the modulation of responses to somatostatin and more complex
      stimuli such as feeding.

PMID- 1352922
TI  - A simple method for affinity purification and PCR amplification of poly(A)+ mRNA.

PMID- 1352921
TI  - The distribution of the CDW52 molecule on blood cells and characterization of its
      involvement in T cell activation.
AB  - The O97 mouse mAb was used to define, together with the CAMPATH-1 mAb series, the
      CDw52 in the course of the Fourth International Workshop on Human Leucocyte
      Differentiation Antigens. O97 and CAMPATH-1M produce full competitive inhibition
      and react with an epitope dependent on O-linked sugar residues. The two mAb,
      however, display significant differences in reactivity with leukocyte populations
      -in fact the reactivity of O97, which also exerts a powerful cytotoxic effect
      with human C', is similar to mAb from the CAM-PATH-1 series having the broadest
      one. Noteworthy, O97 spares PBL, NK, and LAK precursors, permitting an easy
      purification of these cells; O97 is able to kill long-term colony-forming cells
      in bone marrow culture and characteristically reacts, in contrast to CAMPATH-1M,
      with erythrocytes. Western blotting has revealed a strikingly different molecular
      size on red cells, since CDw52 mAb revealed a broad band ranging from 6-16 kDa,
      instead of the 21-28 kDa revealed from leukocyte extracts. In agreement with
      immunofluorescence data, O97 revealed abundant material from red cells in Western
      blotting, while reactivity of CAMPATH-1M was very faint. Overall, these results
      show that distinct molecular forms of the CDw52 molecules are present on
      different blood cells. We have also characterized an activation signal that can
      be delivered to T cells via the CDw52 molecule by CAMPATH-1M but not by O97. This
      is an accessory signal that can complement a primary activation signal delivered
      via the CD2 pathway but not via the CD3-TcR pathway. This is similar to the
      effects obtained with the CD45R (2H4) mAb, 2H4 and CAMPATH-1M mAb having additive
      effects on T cell activation via CD2.

PMID- 1352923
TI  - Active enantiomers may cause adverse effects in asthma.

PMID- 1352924
TI  - [Health-economic aspects of newer anti-ulcer drugs].
AB  - Peptic ulceration is a common condition and is associated with considerable
      expense. Introduction of H2-blockers in the latter part of the nineteen seventies
      offered a new and effective therapeutic alternative for the patient with chronic
      peptic ulceration. On the basis of a review of the literature, the present
      authors have attempted to assess the consequences of the introduction of H2
      blockers for the expenses of peptic ulceration. Introduction of medication is
      found to have reduced the expenses involved in peptic ulceration on account of
      elective operations but on account of the increased costs of medication, the
      total direct costs involved in the treatment of peptic ulceration have possibly
      increased after the introduction of the medication. Attempts are made to compare
      this with the reduction in the indirect costs achieved by reduction in loss of
      production involved by fewer early retirals and sick leaves on account of peptic
      ulceration, fewer deaths connected with peptic ulceration among young persons
      and, in general, improved quality of life for patients with peptic ulceration
      although it is difficult to provide a valid estimation of the savings involved.

PMID- 1352925
TI  - Characterization and activation requirements of bovine lymphocytes acquiring
      cytotoxic activity after interleukin-2 treatment.
AB  - Interleukin-2 (IL-2) treatment of cells and generation of non-major
      histocompatibility complex (MHC)-restricted cytotoxic cells from peripheral blood
      mononuclear leukocytes (PBML) was studied. Effector-target conjugate assays
      demonstrated that bovine PBML bound but did not lyse K562, HL60S and HL60R cells
      unless activated with IL-2. The magnitude of IL-2-activated killing of tumor
      cells as well as the magnitude of antibody-dependent cellular cytotoxicity
      depended on the IL-2 concentration. A short treatment (12-18 h) of effector cells
      with IL-2 was sufficient for development of cytotoxic activity. Withdrawal of IL
      2 from the culture resulted in a reduction of cytotoxic activity that could be
      restored by further addition of IL-2. Cytotoxic activity of IL-2-activated
      populations obtained after nylon wool or Sephadex G-10 passage, and Percoll
      gradient centrifugation of PBML suggests that lymphokine-activated killer (LAK)
      cell activity in PBML is mainly mediated by a non-adherent lymphocyte lacking
      markers for B-cells. Positive and negative selection experiments using cell
      sorting confirmed these findings and demonstrated that the cell responsible for
      LAK cell activity in cattle belongs to a non-monocyte, non-B, CD2+ lymphocyte
      population. Furthermore, cytotoxic activity could not be generated in CD2+
      populations enriched for cells expressing molecules equivalent to human and
      murine CD4 and CD8. These findings suggest that effector cells mediating non MHC
      restricted cytotoxicity in cattle prevail in a population bearing a CD2+, CD4-,
      CD8- phenotype and that this population depends on the continuous presence of IL
      2 for optimal cytotoxic function.

PMID- 1352926
TI  - Leucocyte adhesion protein deficiency in Irish setter dogs.
AB  - Investigation of 12 Irish setter puppies from six litters with severe recurrent
      infections, neutrophilia and low body weight revealed a leucocyte adhesion
      protein deficiency with a total lack of CD11b and CD18. Their neutrophil function
      was severely impaired with a totally absent capacity to ingest C3b-opsonized
      particles, a significantly impaired capacity to ingest IgG-opsonized particles
      and significantly diminished adherence to nylon wool when compared with
      neutrophils from healthy control dogs. The chemiluminescence of patient
      neutrophils activated by C3b-opsonized particles was, consequently, significantly
      decreased compared with that of control neutrophils, while the respiratory burst
      assayed by phorbolmyristate acid (PMA) stimulated nitroblue tetrazolium (NBT)
      reduction was normal in the patient group. Random migration and chemotactic
      responses of patient and control neutrophils, were similar. The etiology,
      pathogenesis and clinical manifestations of the Irish setter leucocyte adhesion
      deficiency were similar to that of the leucocyte adhesion deficiency in humans.

PMID- 1352927
TI  - [Multicenter study of isradipine in the treatment of hypertension].
AB  - MIS is a one-year Multicentre Isradipine Study of the treatment of essential
      hypertension, in which participated seven centres in Czechoslovakia. The study
      comprised 144 patients with mild or medium severe hypertension. Isradipine
      belongs into the group of dihydropyridine derivatives with a high specific and
      low non-specific affinity to dihydropyridine binding sites of the L-type of
      calcium channels. After a four-week placebo period isradipine treatment (2.5 mg
      (1/2 tablet twice a day/was started. This dose increased to 5 mg (1 tablet twice
      a day) unless normalization of the diastolic pressure was achieved by a smaller
      dose. Monotherapy with isradipine normalized the diastolic pressure (less than 90
      mmHg) in 44% of the hypertonic patients. 56% hypertonics where monotherapy with
      isradipine did not reduce the diastolic pressure below 90 mmHg were treated by a
      combination of isradipine and bopindolol. This group of patients had a
      significantly higher systolic and diastolic pressure, a higher number of
      erythrocytes and thrombocytes at the onset of the investigation. Addition of
      bopindolol to isradipine proved very effective. At the end of the one-year study
      87% of the patients had a normal diastolic pressure. Isradipine as monotherapy
      and combined with bopindolol did not influence the metabolic risk factors of IHD
      and drug tolerance was very good.

PMID- 1352928
TI  - The metabolism of imiloxan hydrochloride in healthy male volunteers.
AB  - 1. The metabolism of imiloxan hydrochloride [(+-)-2-(1-ethyl-2-imidazoyl)methyl
      1,4-benzodioxane hydrochloride], an alpha 2-adrenoceptor antagonist, was studied
      in four male volunteers given a 500 mg oral dose containing 0.48 MBq of the 14C
      labelled material. Compound-related radioactivity was rapidly excreted chiefly in
      the urine within 24 h of dosing. 2. Metabolites derived by initial oxidation on
      either or both the benzodioxane and imidazoyl moieties followed by glucuronic
      acid and sulphate conjugation, and an N-glucuronide of imiloxan were tentatively
      identified in urine. 3. The major urinary metabolites, comprising some 37-41% of
      the dose, appeared to be +-2-(1-ethyl-2-imidazoyl)methyl-1,4-benzodioxane-6/7
      sulphonic acid (19% of dose), [+-2-(1-ethyl-2-imidazoyl)methyl-1,4-benzodioxane-
      6/7-ylium D-glucopyranoside]uronate (10-14% of dose), and a glucuronide conjugate
      of +-2-(1-ethyl-2-imidazoyl-4/5-hydroxy)methyl-1,4-benzodioxane (8% of dose).

PMID- 1352929
TI  - [3rd workshop "Experimental and Clinical Liver Transplantation and Hepatology".
      Wilsede, 21-24 May 1992. Abstracts].

PMID- 1352930
TI  - A randomized placebo controlled trial on the effects of simvastatin, a HMG-CoA
      reductase inhibitor, on blood lipids and fibrinolytic parameters.
AB  - Coronary artery disease is frequently associated with disturbed blood lipids and
      with a deficient blood fibrinolytic capacity. In order to investigate a possible
      link between hypercholesterolemia and hypofibrinolysis, we have investigated the
      effect of simvastatin, a HMG-CoA reductase inhibitor, on blood lipids and
      fibrinolytic parameters in a double blind, randomized, placebo controlled study
      design. Twenty-four male patients, aged between 42 and 65 years, with
      angiographically confirmed coronary artery disease, were selected from a series
      of 731 consecutive patients on the basis of a fasting serum cholesterol level of
      more than 250 mg/dl and a plasma PAI-1 level of more than 60 ng/ml. Patients were
      randomly assigned to 20 mg of simvastatin daily (Group I), or placebo (Group II),
      for four weeks, followed by doubling of the dose for another four weeks. Blood
      samples were obtained at baseline and at 4 and 8 weeks. Groups I and II did not
      differ significantly at baseline. As expected, simvastatin produced a significant
      reduction in serum levels of total cholesterol (33 +/- 12 and 36 +/- 12 percent,
      mean +/- SD, after 4 and 8 weeks respectively, p less than 0.001 vs baseline),
      LDL-cholesterol (36 +/- 5 and 43 +/- 6 percent respectively, p less than 0.001 vs
      baseline) and apolipoprotein-B (20 +/- 29 and 23 +/- 30 percent respectively, p
      less than 0.05 vs baseline), whereas these parameters did not change
      significantly in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352931
TI  - Alfentanil combined with vecuronium or pancuronium: haemodynamic implications.
AB  - Forty-two fit, anticholinergized patients, induced with thiopentone, received
      either vecuronium (V) or pancuronium (P) 0.1 mg/kg, followed by alfentanil 15
      micrograms/kg. The mean heart rate in the Group V was significantly lower than
      that in the Group P. The difference, 10-15 bpm, appeared after alfentanil
      administration, and lasted for 5 min postintubation, when under N2O anaesthesia.
      The Group P patients maintained their arterial pressure closer to the
      preinduction level than did the Group V patients, but a statistically significant
      inter-group difference appeared only at two recording stages. Four Group V
      patients, contrasted to none of the Group P patients (P less than 0.05), were put
      in head-down tilt, or were given atropine, and/or etilephrine for an undue
      decrease in arterial pressure. Compared to vecuronium, pancuronium increased
      heart rate, and protected from arterial hypotension, when combined with low-dose
      alfentanil.

PMID- 1352933
TI  - Transactions of the XXIVth Congress of the Scandinavian Oto-laryngological
      Society. Reykjavik, June 19-22, 1990.

PMID- 1352932
TI  - In situ characterization of mononuclear cells in marginal periodontitis of
      patients with Down's syndrome.
AB  - An indirect immunofluorescence technique on cryostat sections was used to study
      the cellular composition in chronic marginal periodontitis (CMP) of patients with
      Down's syndrome (DS). The findings were compared with CMP lesions in otherwise
      normal patients (NP). The distribution and amount of CD22+ cells (B lymphocytes),
      CD3+ cells (pan T lymphocytes), CD4+ cells (helper T subset), CD8+ cells
      (suppressor/cytotoxic T subset), and CD11c+ cells (in tissue, mainly monocytes
      and macrophages) were investigated. Morphologic studies showed a denser
      inflammatory infiltrate in DS than in NP. Countings showed significant
      differences in cell distribution (p = 0.0003) and cell profiles (p = 0.0273)
      between the two groups. The median CD4+/CD8+ ratio in DS (2.73) was significantly
      higher (p = 0.0024) than found in gingival inflammatory lesions from NP (1.08).
      The present study shows that DS patients have a different, more pronounced,
      immune response in CMP than NP.

PMID- 1352935
TI  - Noradrenaline- and glutamate-induced taurine release from bulk isolated adult rat
      astrocytes.
AB  - The influence of noradrenaline and various agonists of glutamatergic receptors on
      preloaded [3H]taurine release from bulk isolated adult rat brain astrocytes was
      investigated by a superfusion technique. In the presence of 1 mM noradrenaline a
      stimulation of taurine release, resembling that observed in astroglial cultures,
      was preceded by an inhibition of the efflux, thus demonstrating different
      dynamics of noradrenaline-evoked taurine release from that observed with beta
      agonists on cultured astroglia. Application of 1 mM glutamate and kainate
      produced stimulation of the release, while 1 mM N-methyl-D-aspartate (NMDA) and 1
      mM NMDA together with 65 mM K+ had no effect on the [3H]taurine release. These
      data suggest the presence of kainate-sensitive and the absence of NMDA-sensitive
      glutamate receptors on bulk isolated astrocytes, which is consistent with
      previous observations on astrocytes in culture.

PMID- 1352934
TI  - The onset of dopaminergic innervation during ontogeny decreases melanotrope
      proliferation in the intermediate lobe of the rat pituitary.
AB  - The onset of dopaminergic innervation and its effects on melanotrope
      proliferation were investigated in the rat pituitary intermediate lobe. Dopamine,
      and its synthetic rate-limiting enzyme tyrosine hydroxylase, were first detected
      immunohistochemically on late post-natal day 3 or early postnatal day 4. Axon
      density was highest at the neural lobe/intermediate lobe border, and decreased
      toward the pituitary cleft. By postnatal day 10, the adult pattern of tyrosine
      hydroxylase immunoreactivity was established and remained through post-natal day
      14. Neurointermediate lobe dopamine levels, measured by HPLC, correlated well
      with the increased axon density observed in the immunohistochemical studies.
      Dopamine could not be measured by our assay (100 fg limit) until post-natal day 3
      (439.32 fg/NIL). Dopamine concentration increased to 2.09 +/- 0.425 ng at PN 4,
      86.31 +/- 20.42 ng at PN 7, 168.72 +/- 18.37 ng at PN 10. Melanotrope
      proliferation was determined by [3H]thymidine incorporation before and after
      innervation. Concomitant with the onset of innervation, the proliferation index
      dropped from 13.4 +/- 0.01% to 6.5 +/- 0.002% at PN 4, and continued to decrease
      until a level of 3 +/- 0.003% was established by PN 10. To confirm the inhibitory
      action of dopaminergic innervation on melanotrope proliferation, rat neonates
      were injected intracisternally with 150 mg 6-hydroxydopamine to destroy
      dopaminergic axons within the intermediate lobe. Measurement of dopamine
      concentrations in neurointermediate lobes of injected animals showed a decrease
      in dopamine levels as compared to controls. From PN 4 (0.88 +/- 0.165 ng), DA
      levels gradually increased during development: at PN 5, [DA] = 0.689 +/- 0.104
      ng; PN 6 [DA] = 11.60 +/- 2.24 ng; PN 7 [DA] = 20.93 +/- 3.80 ng; and PN 10 [DA]
      = 27.95 +/- 3.46 ng. Melanotrope proliferation also increased in 6
      hydroxydopamine-treated animals. At PN 4, the onset of innervation reduced the
      pre-innervation proliferation index to 8.75 +/- 0.002%, only a 30% reduction in
      contrast to the greater than 50% decrease observed in control animals. A stable
      proliferation level of approximately 7.5% persisted in all subsequent stages with
      6-OHDA administration. Our results demonstrated the time of dopamine innervation
      onset and a characteristic developmental pattern for axons within the rat
      intermediate lobe. The onset of innervation and increased dopamine concentration
      suggests increased dopaminergic control of the melanotropes, illustrated
      specifically by a decrease in their level of proliferation. This is the first
      presentation of evidence showing that dopaminergic innervation within the
      intermediate lobe of the rat pituitary regulates melanotrope proliferation.

PMID- 1352937
TI  - Involvement of arachidonic acid and its metabolites in the inhibitory effect of
      beta-adrenoceptor blocking drugs on blood platelets.
AB  - Propranolol (PRO), alprenolol (ALP), metipranolol (MET) and oxprenolol (OXP)
      inhibited arachidonic acid (AA) liberation from membrane phospholipids,
      malondialdehyde (MDA) formation and thromboxane B2 (TXB2) production in
      stimulated platelets. The inhibition was dose-dependent and with slight
      variations followed the rank order of potency: PRO greater than or equal to ALP
      greater than or equal to MET greater than or equal to OXP. Atenolol (ATE) was
      without any inhibitory effect. Inhibition of the arachidonic acid pathway in
      stimulated platelets may significantly contribute to the antiaggregatory effect
      of beta-adrenoceptor blocking drugs.

PMID- 1352936
TI  - Study of the mechanism of prostacyclin (PgI2) action on myocardial contractility.
AB  - The experiments done on the isolated right ventricle of rat heart suspended in
      the bath for isolated organs with oxygenated Tyrode's solution showed the PgI2
      (2.3 x 10-6 mmol) produced its positive inotropic effect indirectly by promoting
      both beta-adrenoreceptors and calcium entry through slow calcium channels because
      this effect could be blocked by propranolol (2.3 x 10-2 mmol - beta
      adrenoreceptor blocker) or verapamil (4.3 x 10-3 mmol - slow calcium channel
      blocker).

PMID- 1352938
TI  - [Anterior urethral diverticular stones and retrocaval ureter in male: a case
      report and review of literature in Japan].
AB  - A case of diverticular stones in the male anterior urethra with retrocaval ureter
      is reported. A 26-year-old man visited our hospital for examination, who had
      experienced spontaneous stone discharge a few days earlier. Computed tomographic
      (CT) scan with ureteral catheterization and urethrography revealed a retrocaval
      ureter and urethral diverticular stones. Resection of urethral diverticulum with
      7 stones and right ureteroplasty were performed. The urethrography and drip
      infusion pyelography (DIP) 9 months after operation showed no abnormal findings.
      The largest stone was 28 x 22 x 20 mm in size and 20 g in weight. The main
      components were ammonium dihydrogen-urate (70%), carbonate apatite and struvite.
      Histological feature of the epithelium of the urethral diverticulum indicated
      normal skin with hairs. Pathological diagnosis was para-urethral dermoid cyst.
      Our case is the 67th case of the male urethral diverticular stones and the first
      case of those with retrocaval ureter in Japan.

PMID- 1352939
TI  - Pulmonary artery disease in Takayasu's arteritis: angiographic findings.
AB  - One hundred sixteen arteriographic examinations in 98 patients with Takayasu's
      arteritis were studied retrospectively to evaluate the extent of aortic and
      pulmonary disease. Stenosis was the most frequent finding in the aorta and its
      branches, but occlusion, dilatation, and aneurysms were also seen. Adventitial
      vascular structures, consistent with dilated vasa vasorum, were observed in five
      patients (5%) and systemic artery-pulmonary artery communication was seen in six
      (6%). Twenty-one (70%) of 30 patients who had pulmonary arteriography were shown
      to have pulmonary artery involvement. Upper lobe pulmonary arterial branches
      showed abnormalities most frequently; segmental branches, followed by
      subsegmental branches, were most often involved. The frequency of abnormal
      findings on pulmonary arteriograms correlated with the number of involved
      brachiocephalic vessels. Stenotic lesions in the aorta and its branches
      progressed in five (45%) of 11 patients, and those in the pulmonary artery
      progressed in one (33%) of three cases. Takayasu's arteritis characteristically
      involves the systemic and pulmonary arteries, and the extent of arteritis in the
      major branches of the aortic arch appears to correlate with pulmonary arterial
      involvement. Both thoracic and abdominal aortographic studies and pulmonary
      arteriography are necessary to properly diagnose the extent of the disease, and
      angiography should be repeated for appropriate patient follow-up.

PMID- 1352941
TI  - Sipple syndrome with lichen amyloidosis as a paracrinopathy.

PMID- 1352940
TI  - Predictors of the risk of development of acquired immunodeficiency syndrome
      within 24 months among gay men seropositive for human immunodeficiency virus type
      1: a report from the Multicenter AIDS Cohort Study.
AB  - The natural history of infection with human immunodeficiency virus type 1 (HIV-1)
      is characterized by a relentless decline in CD4-positive lymphocytes and the
      ultimate development of acquired immunodeficiency syndrome (AIDS). However,
      variables other than the CD4-positive lymphocyte level contribute to the
      measurement of risk for AIDS and can be used as predictors of AIDS onset. This
      study was undertaken to identify factors that, independently of the CD4-positive
      lymphocyte level, would predict the risk of AIDS over 24 months in a cohort of
      HIV-1 seropositive homosexual men receiving no antiretroviral therapy.
      Demographic, clinical, and laboratory data from 1,325 white, HIV-1 seropositive
      participants in the Multicenter AIDS Cohort Study who have been studied for 4
      years were analyzed with univariate and multivariate methods. To control for
      stage of infection, the baseline percentage of CD4-positive lymphocytes (a known
      marker of disease progression), and the decline of CD4-positive cells during the
      first 6 months of observation were used as continuous variables. The variables
      that were independently associated with an increased risk of developing AIDS
      were: low baseline CD4 percentage, decline in the CD4 percentage during the first
      6 months of follow-up, the presence of serum immunoglobulin A at baseline,
      decrease in hemoglobin during the first 6 months of follow-up, incident fatigue,
      and the interaction of decline in the CD4 percentage and incident thrush. While
      low CD4 percentage and other variables have been previously described as
      prognostic markers, decline in the CD4 percentage and the interaction of that
      decline and incident thrush have not previously been described as being of
      prognostic importance. These variables and the analytic method for estimating
      prognosis may prove useful for selecting and evaluating antiretroviral therapy,
      instituting prophylactic measures against certain opportunistic infections, and
      recruitment into clinical trials. Because study participants received no
      antiretroviral prophylaxis during the period under analysis, the method could be
      used to estimate the prognosis for those receiving investigational treatment were
      they to remain untreated, effectively making any participant in a clinical trial
      his own untreated control.

PMID- 1352942
TI  - Inconsistency of the immunophenotype of Reed-Sternberg cells in simultaneous and
      consecutive specimens from the same patients. A paraffin section evaluation in 56
      patients.
AB  - Both immunophenotypic overlaps between Hodgkin's disease (HD) and non-Hodgkin's
      lymphoma (NHL), and evolution of one into the other have been reported. However,
      the underlying assumption that the antigenic expression of Reed-Sternberg (RS)
      cells is consistent in the same patient has not been evaluated. Such an
      evaluation was undertaken by immunophenotyping paraffin-embedded lymphoid tissue
      biopsies with HD from 56 patients in whom multiple specimens were obtained,
      either simultaneously from different sites or at different times. The panel of
      antibodies we used included: CD3 polyclonal antiserum, DAKO-M1 (CD15), L26
      (CD20), BerH2 (CD30), MT1 (CD43), DAKO-LCA (CD45RB), UCHL1 (CD45R0), LN2 (CD74),
      and DAKO-EMA. The phenotype of RS cells was identical in simultaneous biopsies in
      only 11 of 39 patients (28%) and remained constant in consecutive biopsies in
      only 4 of 21 patients (19%). Major differences (relative to cell lineage specific
      antigens) were observed in 10 of 39 patients with simultaneous biopsies and in 10
      of 21 patients over time; they mainly involved expression of T-cell antigens.
      Minor differences (relative to any other antigen) were observed in 22 of 39
      patients with simultaneous biopsies and in 15 of 21 patients over time; these
      mainly involved CD15 or CD74. This striking variability of the immunophenotype of
      RS cells in the same patient may be due to aberrant marker expression, as a
      result of the neoplastic state, and/or to modulation of antigenic expression in
      relation to the host environment. This inconsistency suggests caution when
      interpreting the relationship between HD and NHL by paraffin immunophenotyping
      alone.

PMID- 1352943
TI  - PCNA expression in cutaneous keratinous neoplasms and verruca vulgaris.
AB  - Using an antibody to PCNA and a standard immunohistochemical system, the authors
      examined normal epidermis and cutaneous neoplasias for expression of PCNA, a
      protein associated with DNA polymerase delta and DNA replication. In squamous
      cell carcinoma in situ (SCCI), a unique expression of PCNA, which frequently
      involved the nuclei of all keratinocytes within the lesion, was found. Heaviest
      staining was in the uppermost layers of the epidermis. PCNA expression ended
      abruptly at the histologic margin of the lesion. Because SCCI can be associated
      with the presence of human papillomavirus (HPV) DNA, the authors evaluated PCNA
      expression in verruca vulgaris and found a pattern similar to that in SCCI.
      Assuming that PCNA expression in these two lesions is related to cell division,
      the authors hypothesize that the mechanisms that control proliferation in SCCI
      may be similar to those operative in verruca vulgaris.

PMID- 1352944
TI  - Bauhinia purpurea--a new paraffin section marker for Reed-Sternberg cells of
      Hodgkin's disease. A comparison with Leu-M1 (CD15), LN2 (CD74), peanut
      agglutinin, and Ber-H2 (CD30).
AB  - Thirty-three cases of Hodgkin's disease (thirteen nodular sclerosis, four
      diffuse, lymphocyte predominance, and sixteen mixed cellularity) were studied
      with Bauhinia purpurea (BPA), peanut agglutinin (PNA), anti-Leu-M1, LN2, and Ber
      H2 by the avidinbiotin-peroxidase complex (ABC) method in paraffin sections. Reed
      Sternberg (RS) cells and variants were stained positively with one or more of the
      reagents in all cases. BPA staining was positive in 32 of 33 cases (97.0%), PNA
      staining was positive in 23 of 33 cases (69.7%), Leu-M1 was positive in 13 of 33
      cases (39.4%), LN2 was positive in 14 of 33 cases (42.4%), and Ber-H2 was
      positive in 24 of 33 cases (72.7%). Many RS cells were stained moderately to
      strongly and were readily recognized in 31 cases (96.9%) of BPA+, 10 (43.5%) of
      PNA+, 8 (61.5%) of Leu-M1+, 6 (42.9%) of LN2+, and 22 (91.7%) of Ber-H2+ cases;
      in the remaining positive cases, the RS cells were found only after careful
      searching. Three staining patterns were recognized: paranuclear, diffuse
      cytoplasmic, and membranous. These three patterns were obtained with all markers
      except for LN2. LN2 showed diffuse cytoplasmic staining in most of the positive
      cells, and a few cells showed paranuclear deposits. BPA reactivity was not
      affected by formalin fixation or paraffin embedding. Except for RS cells, BPA
      also showed dense cytoplasmic staining reaction with macrophage-histiocytes.
      Sixty cases of non-Hodgkin's diffuse lymphomas (30 T- and 30 B-cell origin) were
      also studied. Tumor cells were not stained with BPA, PNA, and Leu-M1, but stained
      positively with LN2 in six T-cell lymphomas and thirteen B-cell lymphomas, and
      with Ber-H2 in six T-cell lymphomas and one B-cell lymphoma. In conclusion, to
      facilitate the detection of RS cells and related variants in paraffin sections,
      BPA can be accepted as a useful marker due to its high-detection rate,
      reproducible staining pattern, and resistance to fixatives.

PMID- 1352945
TI  - Restriction fragment length polymorphism analysis of ERBB2 oncogene by capillary
      electrophoresis.
AB  - Capillary electrophoresis (CE) with a sieving buffer containing ethidium bromide
      was applied to the detection of PCR-amplified RFLP samples. With CE, in contrast
      to agarose gel electrophoresis, run times are short, i.e., typically less than 30
      min, the capillary can be re-used, and full automation is feasible. The addition
      of ethidium bromide to the buffer system in conjunction with a field
      amplification injection technique led to increased sample detectability and
      resolution. Migration time precision was better than 0.2% RSD with a
      approximately 12-bp resolution for the DNA fragment sizes of interest. RFLP
      samples were analyzed for homo- or heterozygosity based on the presence of 500-
      and/or 520-bp DNA fragments. Special software was used to correct for run-to-run
      migration time variations, thus facilitating genotype assignment.

PMID- 1352946
TI  - Assay of apical membrane enzymes based on fluorogenic substrates.
AB  - A series of enzymatic rate assays are described. The assays are based on coumarin
      derivatives that are fluorogenic substrates for the enzymes dipeptidase IV,
      aminopeptidase N, alkaline phosphatase, and gamma-glutamyltransferase. These
      simple assays are rapid and offer improved sensitivity over established
      colorimetric methods. The substrates have apparent affinities for the enzymes of
      5-250 microM. L-Glutamic acid gamma-(7-amido-4-methylcoumarin) is characterized
      as a substrate of gamma-glutamyltransferase on the basis of inhibition of
      enzymatic cleavage when the glycylglycine acceptor molecule is omitted and
      inhibition of the enzymatic reaction by addition of glycine. Assay conditions for
      the four enzymes are established such that less than 0.6% of the substrate is
      consumed, fluorescence is proportional to enzymatic product, and results may be
      directly compared to established colorimetric assays. Intestinal epithelial cells
      are used both to establish appropriate assay conditions and to demonstrate the
      utility of the assays.

PMID- 1352947
TI  - Determination of glutamic acid decarboxylase activity and inhibition by an H2O2
      sensing glutamic acid oxidase biosensor.
AB  - The catalytic activity of the enzyme L-glutamic acid decarboxylase (GAD) is
      determined by an amperometric method based on a recently developed glutamate
      selective biosensor. The biosensor is composed of an amperometric H2O2 electrode
      and a biocatalytic membrane containing the enzyme glutamic acid oxidase (GAO).
      The biosensor allows the direct and continuous measurement of GA levels by
      monitoring the H2O2 produced at the electrode interface as a coproduct of the GAO
      catalyzed GA oxidation to alpha-ketoglutaric acid. Since GA is transformed to
      gamma-aminobutyric acid and CO2 under the catalytic activity of GAD, the rate of
      GA consumption in solution, monitored by the GAO biosensor, represents a reliable
      measure of GAD catalytic activity. Additional experiments performed in the
      presence of different concentrations of the GAD inhibitor valproic acid have
      shown the suitability of the proposed approach for the study of GAD inhibitors
      also. Discussion of the main experimental characteristics of this new analytical
      method is given in terms of sensitivity, reproducibility, and reliability of the
      experimental results and ease, time, and cost of operation.

PMID- 1352948
TI  - A fluorometric, high-performance liquid chromatographic assay for
      transglutaminase activity.
AB  - A fluorometric, high-performance liquid chromatographic assay for
      transglutaminase activity is described. The method uses the small synthetic
      peptide benzyloxycarbonyl-L-glutaminylglycine and the fluorescent amine
      monodansylcadaverine as substrates. Very small amounts of substrates and enzyme
      are required for this assay. The reaction product is separated from substrates on
      a reversed-phase, C-18 column, using an isocratic elution solvent consisting of
      50% methanol in water, and is detected fluorometrically with didansylcadaverine
      as standard. A detection limit of 31 pmol of product per injection was measured.
      An apparent Km of 34.7 +/- 2.4 mM was determined for the peptide substrate with
      purified guinea pig liver enzyme. Using this assay, a series of alkyl aldehydes
      was shown to inhibit transglutaminase. Modification of this assay using either
      gradient or isocratic elution with various proportions of acetonitrile (0.1%
      trifluoroacetic acid)/water (0.1% trifluoroacetic acid) afforded assays for a
      series of glutamine-containing peptides including substance P, alpha-endorphin,
      and two small, synthetic peptides. The assay is suitable for measurement of
      transglutaminase activity with purified enzyme or with crude preparations. This
      method provides a sensitive, quantitative assay for the determination of
      substrate and inhibitor properties of small peptides toward transglutaminases.

PMID- 1352949
TI  - Esmolol is more effective than sodium nitroprusside in reducing blood loss during
      orthognathic surgery.
AB  - The goal of this study was to compare the efficacy of esmolol and sodium
      nitroprusside (SNP) as primary drugs for producing controlled hypotension and
      limiting blood loss during orthognathic surgery. Thirty ASA physical status I and
      II patients (mean age 22 yr) undergoing LeFort I maxillary osteotomies were
      randomly assigned to receive either esmolol (n = 15) or SNP (n = 15) as the
      primary drug to induce hypotension. All patients received a balanced anesthetic
      technique including isoflurane, with controlled hypotension during the
      downfracture of the maxilla. Patients assigned to the esmolol treatment group
      received boluses of 500 micrograms/kg of esmolol, followed by a continuous
      infusion of 100-300 micrograms.kg-1.min-1, and the SNP treatment group received a
      continuous infusion of SNP at 0.25-4.00 micrograms.kg-1.min-1; both infusions
      were titrated to obtain a mean arterial blood pressure within the target range of
      55-65 mm Hg. The mean arterial blood pressure during the hypotensive period was
      58.7 +/- 0.7 (mean +/- SEM) and 61.8 +/- 0.4 mm Hg for esmolol and SNP,
      respectively (P less than 0.001). In addition, 40% +/- 4% of the observed values
      in the esmolol group and 53% +/- 3% in the SNP group were outside the target
      range for mean arterial blood pressure (difference significant at P less than
      0.05), and a greater proportion of the deviations were above 65 mm Hg in the SNP
      group than in the esmolol group (0.64 vs 0.46, respectively, P less than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352950
TI  - Intracranial pressure effects of dexmedetomidine in rabbits.
AB  - The alpha 2-adrenergic receptor agonist dexmedetomidine produces an anesthetic
      state in a variety of species. Although its effects on cerebral blood flow and
      the electroencephalogram have been investigated, the effect of this drug on
      intracranial pressure (ICP) has not been reported previously. Dexmedetomidine
      therefore was intravenously administered to 24 New Zealand white rabbits that had
      been anesthetized with halothane and mechanically ventilated to maintain a
      constant arterial CO2 tension (PaCO2) between 34 and 39 mm Hg. After placement of
      an arterial catheter and ventricular cannula, baseline measurements of monitored
      variables, including heart rate, mean arterial blood pressure, ICP, end-tidal
      CO2, body temperature, and arterial blood gases, were recorded. Dexmedetomidine
      (20, 80, or 320 micrograms/kg IV) or saline solution was then infused over a 10
      min period. The ICP transiently decreased by 31% in the 20-micrograms/kg group
      (from a mean value of 9.4 +/- 1.3 [SEM] to 6.5 +/- 1.0 mm Hg, P less than 0.05).
      In the 320-micrograms/kg group, ICP remained unchanged over the course of the
      study despite a significant increase in arterial blood pressure (32 mm Hg). The
      effects of dexmedetomidine on ICP were next investigated in the presence of
      intracranial hypertension produced by a cryogenic lesion (mean baseline ICP 16.8
      mm Hg). In addition to the previously monitored variables, sagittal sinus blood
      flow was measured by the hydrogen clearance technique before and after the
      administration of dexmedetomidine (320 micrograms/kg IV). In these experiments,
      dexmedetomidine was associated with a 14% decrease in sagittal sinus blood flow
      that was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1352951
TI  - The Neurobiology of Drug and Alcohol Addiction. New York Academy of Sciences
      conference. Spokane, Washington, July 23-26, 1991.

PMID- 1352952
TI  - Alcohol self-administration: role of mesolimbic dopamine.
AB  - It appears clear that ethanol reinforcement, like that of many abused drugs,
      utilizes the mesolimbic DA pathways. From the data presented on microinjection of
      DA agonists and antagonists, it would seem that only part of the regulatory
      process controlling ethanol drinking is directly involved with this pathway. Once
      drinking has begun, the DA antagonist raclopride results in a rapid termination
      of drinking. This appears to be a blocking effect of what may be conditioned
      reinforcement resulting from prior ethanol reinforcement initiation procedures.
      Microinjection of the DA agonists d-amphetamine and quinpirole prolonged
      drinking, with little signs of normal termination apparent in the 30-min session
      in many animals. This appeared to be the result of interference with normal
      termination processes. While it remains to be demonstrated that oral ethanol
      consumption results in the release of DA in the nucleus accumbens, evidence from
      prior work and the present studies support a role for the mesolimbic DA system in
      ethanol reinforcement.

PMID- 1352953
TI  - Behavioral sensitization induced by psychostimulants or stress: search for a
      molecular basis and evidence for a CRF-dependent phenomenon.

PMID- 1352954
TI  - Effects of withdrawal from chronic cocaine administration on behavior and beta
      adrenergic and serotonergic brain receptors in rat.

PMID- 1352955
TI  - Evaluation of anxiolytic action of ondansetron in rats during withdrawal from
      chronic chlordiazepoxide.

PMID- 1352958
TI  - Tooth mutilations in pre-Columbian Peru and Chile and modern-day Nigeria.
AB  - Tooth mutilation or adornment in ancient Peru and Chile is discussed as well as
      that seen in present day Nigeria. Dental mutilation must be recognized
      (diagnosed) for what it is and discouraged in order to prevent dentoalveolar
      pathology and tooth loss.

PMID- 1352956
TI  - GABA and nucleus accumbens glutamate neurotransmission modulate ethanol self
      administration in rats.

PMID- 1352957
TI  - Common intracellular actions of chronic morphine and cocaine in dopaminergic
      brain reward regions.

PMID- 1352959
TI  - Ethacrynic acid inhibition of microtubule assembly in vitro.
AB  - Ethacrynic acid (ECA) is a sulfhydryl reactive diuretic drug. Recent studies show
      that ocular administration of ECA may have potential efficacy for treatment of
      glaucoma. ECA affects cell shape in cultured cells from the eye outflow pathway
      and the microtubule system is disrupted. We have studied the effect of ECA on
      microtubule protein (MTP) (tubulin and microtubule-associated proteins) and
      purified tubulin assembly. Fifty percent inhibition of MTP (1.8 mg/ml) assembly
      was found at 70 microM ECA in buffer and 410 microM ECA in 30% glycerol in
      buffer. If all sulfhydryl groups were attributed to tubulin, then approximately
      two sulfhydryls were blocked at 50% inhibition. Tubulin (2 mg/ml) assembly showed
      50% inhibition at 175 microM ECA and approximately 2 sulfhydryl groups were lost.
      Increasing ECA preincubation times (0-60 min) with tubulin showed that the longer
      the preincubation time, the longer the lag time, and the slower the rate of
      assembly and that the percentage of inhibition was proportional to the ECA
      preincubation time. The number of blocked sulfhydryls also increased with
      preincubation time. Approximately two sulfhydryls were blocked at 50% inhibition
      of assembly. The critical concentration for assembly increased twofold when
      tubulin was preincubated with 0.1 mM ECA, suggesting a loss of active tubulin.
      Fifty percent inhibition of taxol-induced MTP and tubulin assembly occurred at
      190 and 280 microM ECA, respectively, with 3.6 to 3.8 sulfhydryls blocked,
      respectively. Taxol protects microtubules from disassembly by ECA, suggesting
      that the ECA binding key sulfhydryls are blocked in the microtubule. These
      results suggest that ECA reacts slowly with tubulin and blocks sulfhydryl groups
      important for assembly. Microtubule-associated proteins and glycerol protect the
      sulfhydryls and so more ECA is necessary to inhibit assembly. Since the number of
      blocked sulfhydryls is greater at 50% inhibition for taxol-induced microtubules,
      sulfhydryl blocked tubulin incompetent to assemble under normal conditions may be
      induced to do so with taxol.

PMID- 1352960
TI  - Characterization of a full-length, active-site mutant of diphtheria toxin.
AB  - A full-length recombinant mutant of diphtheria toxin containing serine in place
      of a crucial active-site glutamate has been purified and characterized. The
      serine substitution caused a minor structural alteration in the toxin as measured
      by trypsinolysis. ADP-ribosyltransferase activity and cytotoxicity of the mutant
      were both decreased by approximately 500-fold. A similar reduction in
      cytotoxicity was found when the enzymic fragments of both the wild-type and
      mutant toxins were introduced into the cytosol of fibroblasts by osmotically
      lysing pinosomes. The mutation did not alter the binding of the toxin to cell
      surface receptors and had no apparent effect on membrane translocation. The
      results suggest that the decreased cytotoxicity of the mutant is solely due to
      the reduced ADP-ribosyltransferase activity.

PMID- 1352962
TI  - Induction of remission in a patient with Takayasu's arteritis by low dose pulses
      of methotrexate.
AB  - A 42 year old woman with Takayasu's arteritis responded to treatment with
      prednisone (60 mg daily) but developed severe side effects. Cyclophosphamide
      treatment did not produce a clinical improvement or steroid sparing effect. A
      treatment trial with a weekly pulse of low dose methotrexate improved her
      symptoms and the patency of her occluded left subclavian artery.

PMID- 1352961
TI  - Ankylosing spondylitis and HLA-B27: restriction fragment length polymorphism and
      sequencing of an HLA-B27 allele from a patient with ankylosing spondylitis.
AB  - Two groups of patients with ankylosing spondylitis (AS) from England and Poland
      were examined for restriction fragment length polymorphisms (RFLPs) associated
      with the disease. No preferential association was found between the 9.2 kb PvuII
      fragment in HLA-B27 positive patients with AS compared with HLA-B27 healthy
      subjects as had been previously reported. In the English group, however, a 14 kb
      PvuII fragment was more common in HLA-B27 positive subjects with AS than in
      normal controls. Also 4.6 and 3.7 kb PvuII fragments were more prevalent in
      subjects without AS than in the group with AS, but these results were confined to
      the English group. Furthermore, the sequence of an HLA-B*2705 gene isolated from
      a patient with AS was examined, and no significant differences were found
      compared with the sequence isolated from a healthy subject. There do not seem to
      be significant genetic differences in the coding or in the regulatory region in
      HLA-B27 alleles, in subjects with or without AS.

PMID- 1352964
TI  - Conference report: 9th International Congress of Radiation Research. Toronto,
      Canada, July 7-12, 1991.

PMID- 1352963
TI  - The Zollinger-Ellison syndrome. A collective surgical experience.
AB  - A retrospective study of 90 surgically treated patients with the Zollinger
      Ellison syndrome seen from 1958 through 1990 was performed. Fifteen patients had
      Zollinger-Ellison syndrome as a manifestation of multiple endocrine neoplasia
      type I. Preoperative tumor localization was positive in 46% of 54 patients
      studied. Gastrinomas were identified in 66% of patients, 38% of the tumors being
      malignant. Postoperative eugastrinemia was achieved in 11% of patients after a
      variety of surgical procedures. Exploratory laparotomy provides the only chance
      for cure and identifies the significant prognostic factors associated with long
      term patient survival: small tumor size, extrapancreatic primary, and absence of
      tumor metastases.

PMID- 1352965
TI  - Correlation among oxysterol potencies in the regulation of the degradation of 3
      hydroxy-3-methylglutaryl CoA reductase, the repression of 3-hydroxy-3
      methylglutaryl CoA synthase and affinities for the oxysterol receptor.
AB  - 25-Hydroxycholesterol regulates cholesterol biosynthesis by two mechanisms:
      repression of the transcription of the genes for several cholesterogenic enzymes
      and acceleration of the degradation of the enzyme 3-hydroxy-3-methylglutaryl CoA
      reductase. In the present work the structural features which govern oxysterol
      potency were determined separately for each regulatory mechanism. Regulation of
      degradation was tested using a 3-hydroxy-3-methylglutaryl CoA reductase-beta
      galactosidase fusion protein. Repression of enzyme synthesis was tested by
      measuring 3-hydroxy-3-methylglutaryl CoA synthase activity since this protein is
      not regulated by a degradative mechanism. Oxysterol activities were highly
      correlated between the two assays (R = .959) demonstrating that the degradative
      and repressor mechanisms share an element which determines oxysterol regulatory
      potency. Correlation of these results with previous data for the affinity of
      these oxysterols for the oxysterol receptor suggests that the receptor is the
      element involved in both these regulatory pathways.

PMID- 1352966
TI  - Inhibition of receptor-stimulated guanylyl cyclase by intracellular calcium ions
      in Dictyostelium cells.
AB  - In Dictyostelium discoideum extracellular cAMP stimulates guanylyl cyclase and
      phospholipase C; the latter enzyme produces Ins(1,4,5)P3 which releases Ca2+ from
      internal stores. The following data indicate that intracellular Ca2+ ions inhibit
      guanylyl cyclase activity. 1) In vitro, Ca2+ inhibits guanylyl cyclase with IC50
      = 41 nM Ca2+ and Hill-coefficient of 2.1. 2) Extracellular Ca2+ does not affect
      basal cGMP levels of intact cells. In electro-permeabilized cells, however, cGMP
      levels are reduced by 85% within 45 s after addition of 10(-6) M Ca2+ to the
      medium; halfmaximal reduction occurs at 200 nM extracellular Ca2+. 3) Receptor
      stimulated activation of guanylyl cyclase in electro-permeabilized cells is also
      inhibited by extracellular Ca2+ with half-maximal effect at 200 nM Ca2+. 4) In
      several mutants an inverse correlation exists between receptor-stimulated
      Ins(1,4,5)P3 production and cGMP formation. We conclude that receptor-stimulated
      cytosolic Ca2+ elevation is a negative regulator of receptor-stimulated guanylyl
      cyclase.

PMID- 1352967
TI  - Amide bond cleavage monitored continuously through detection of a
      dansylcadaverine leaving group.
AB  - The transglutaminase-catalyzed incorporation of the fluorescent amine,
      dansylcadaverine, into casein derivatives, such as N,N-dimethylcasein, is
      accompanied by a large increase in intensity of emission (Lorand et al., Anal.
      Biochem. 44, 221-231, 1971). We have sought to make use of this sensitive
      detection device for the continuous, on-line monitoring of an amide-splitting
      reaction in which dansylcadaverine served as the leaving group. The
      transglutaminase-coupled test system comprised gamma-glutamyldansylcadaverine as
      the first substrate and gamma-glutamylamine cyclotransferase as the enzyme
      responsible for releasing dansylcadaverine from the gamma-amide. At close to
      saturating levels of transglutaminase, the measured rate of increase of
      fluorescence, i.e. the steady-state rate of dansylcadaverine incorporation into
      N,N-dimethylcasein, showed a near-linear relationship with the concentration of
      gamma-glutamylamine cyclotransferase present in the assay mixture. The general
      approach developed may be applicable to the assay of other amide cleaving
      enzymes.

PMID- 1352968
TI  - Differential expression of the neu oncogene in mouse liver and pancreatic cell
      lines.
AB  - To study the tissue-specific expression of neu oncogene, we used two mouse tumor
      cell lines derived from liver, Hep1-a, and pancreatic, 266-6, tumors as a model
      system. The endogenous neu gene is expressed in Hep1-a but not in 266-6 cells. We
      demonstrate in this report that differential expression of the neu gene in these
      two cell lines is mainly regulated at transcriptional level. The neu promoter
      sequence responsible for the differential regulation is localized within a 90 bp
      region and it is possibly due to lack of a specific positive transcription
      factor(s) interacting with this region in 266-6 cells.

PMID- 1352969
TI  - Hsp60/chaperonin gene expression and differentiation of human colon
      adenocarcinoma and multipotent leukaemic cells.
AB  - Elevated mitochondrial gene expression is an early event in the switch from
      proliferation to differentiation of the human colon adenocarcinoma cell line,
      HT29, promoted by trehalose replacement of exogenous glucose. Here we report the
      isolation and elevated expression of hsp60, the gene encoding chaperonin, a
      mitochondrial protein required for assembly of mitochondrial and cellular
      proteins. In contrast to HT29, leukaemic cells (HL60 and K562) neither
      differentiated nor altered their mitochondrial gene expression after treatment
      with trehalose. However, differentiation of these cells, as promoted by 12-O
      tetradecanoylphorbol-13-acetate actually resulted in decreased levels of hsp60
      mRNA expression as well as mitochondrial RNA expression, suggesting significant
      differences in involvement of mitochondria in the differentiation of these cell
      lineages.

PMID- 1352970
TI  - An immunomodulatory protein, Ling Zhi-8, facilitates cellular interaction through
      modulation of adhesion molecules.
AB  - Ling Zhi-8 (LZ-8), a novel immunomodulatory protein, markedly enhanced the
      expression of CD11b, but not CD11a, CD13, CD14, CD18, CD33 or HLA-DR, on the U937
      cell line in a dose-dependent fashion. It also induced ICAM-1 expression on
      vascular endothelial cells and significantly augmented gamma - interferon-induced
      cellular binding between vascular endothelial cells and U937. Furthermore, LZ-8
      increased the expression of CD2, but not VLA4, VLA5 or LFA3, on MOLT4 and
      enhanced rosette formation between human T cells and sheep red blood cells. These
      data suggest that LZ-8 exerts its pharmacological effect by modulating adhesion
      molecules on immunocompetent cells.

PMID- 1352971
TI  - Is a point mutation in the mitochondrial ND2 gene associated with Alzheimer's
      disease.
AB  - A specific mitochondrial DNA mutation at position 5460 in the ND2 gene of the
      human mitochondrial genome was recently reported to exist in 10 of 19 patients
      with Alzheimer's disease, implying an association between this mtDNA mutation and
      the occurrence of the disease. We have analyzed tissues from 15 patients with
      Alzheimer's disease for the presence of the ND2 mutation, and have not been able
      to confirm these findings. We believe that this mutation is not specifically
      associated with Alzheimer's disease, but rather, is a neutral polymorphism
      present in the population.

PMID- 1352972
TI  - Stearoyl-CoA desaturase gene expression in lymphocytes.
AB  - B lymphocytes from the spleens of normal (BALB/c) and autoimmune (MRL/lpr)
      strains of mice express the SCD-2 form of stearoyl-CoA desaturase as opposed to
      the SCD-1 form of the gene which is expressed in liver. However, whereas BALB/c T
      cells did not express SCD-1 or SCD-2, both BALB/c thymocytes and MRL/lpr T cells
      expressed SCD-2, suggesting a developmental down-regulation of SCD-2 within the T
      cell lineage. Northern analyses also revealed the expression of SCD-2 in the T
      cell lines BW5147, CTLL-2 and HT-2 and in BCL1, a B cell line. SCD-1 expression
      was not detected in any of the lymphoid cells tested. Finally, we show that SCD-2
      gene expression is inhibited by arachidonic acid (20:4). These results
      demonstrate the complexity of SCD-2 regulation in lymphoid cells.

PMID- 1352973
TI  - Stereoisomers of calcium antagonists which differ markedly in their potencies as
      calcium blockers are equally effective in modulating drug transport by P
      glycoprotein.
AB  - The (-)-isomer of verapamil is 10-fold more potent as a calcium antagonist than
      the (+)-isomer. However, both enantiomers are equally effective in increasing
      cellular accumulation of anticancer drugs [Gruber et al., Int J Cancer 41: 224
      226, 1988]. In addition to verapamil, there exists a wide variety of
      stereoisomers with phenylalkylamines and dihydropyridine structures which
      markedly differ in their potency as calcium antagonists. We have tested these
      drugs for their ability to increase intracellular accumulation of [3H]vinblastine
      ([3H]VBL) in a doxorubicin-resistant cell line (F4-6RADR) derived from the Friend
      mouse leukemia cell line (F4-6P) and in COS-7 monkey kidney cells. Both cell
      types express substantial amounts of multidrug resistance gene 1 mRNA and P
      glycoprotein as revealed by RNA and immuno blot analysis. The enantiomers with
      phenylalkylamine structures [(+/-)-verapamil; (+/-)-devapamil; (+/-)-emopamil)]
      and with dihydropyridine structures [(+/-)-isradipine; (+/-)-nimodipine; (+/-)
      felodipine; (+/-)-nitrendipine; (+/-)-niguldipine] increased [3H]VBL accumulation
      in both cell lines at micromolar concentrations. Although the stereoisomers of
      these drugs differ markedly in their potency as calcium channel blockers they
      were about equally effective in increasing VBL levels in the cells. There was no
      substantial difference in the potencies of the phenylalkylamine drugs in
      affecting cellular [3H]VBL transport. Major potency differences, however, were
      observed in the dihydropyridine drug series with the niguldipine isomers as the
      most effective drugs. Moreover, the niguldipine enantiomers were equally as
      effective in reversing VBL resistance in F4-6RADR cells as were the verapamil
      enantiomers. Since (-)-niguldipine (B859-35) displays a 45-fold lower affinity
      for calcium channel binding sites than (+)-niguldipine, but is equally potent in
      inhibiting drug transport by P-glycoprotein and in reversing drug resistance, it
      may be, in addition to (+)-verapamil, another useful candidate drug for the
      treatment of multidrug resistance in cancer patients.

PMID- 1352974
TI  - Apolipoprotein B gene polymorphisms, lipoproteins and coronary atherosclerosis: a
      study of young myocardial infarction survivors and healthy population-based
      individuals.
AB  - Association studies were carried out in a sample of 87 patients from Sweden who
      had survived a myocardial infarction (MI) before the age of 45, and 91 age
      matched healthy individuals, to compare the impact of polymorphisms at the
      apolipoprotein (apo) E and B gene loci on among-individual differences in plasma
      lipid traits and progression of atherosclerosis. In the group of healthy
      individuals, polymorphisms creating the common apo E isoforms were, as expected,
      associated with significant differences in total and low density lipoprotein
      (LDL) cholesterol (11.7% and 11.6% of sample variance). For apo B, the
      polymorphism with the largest effect on apo B levels (16% of sample variance) was
      the C to T transition 265 bp 5' of the cap site, in the promoter (detectable by
      MspI). Both this polymorphism and the threonine2488 neutral substitution
      (detectable by XbaI) were associated with significant effects on LDL-cholesterol
      (8.3% and 9.3% of sample variance, respectively). The asparagine/serine4311
      polymorphism was associated with a significant effect on high density lipoprotein
      (HDL) cholesterol alone, and there was no significant association with the
      glutamate/lysine4154 polymorphism (detectable by EcoRI) or the leucine-alanine
      leucine (LAL) insertion/deletion polymorphism in the signal peptide. In the
      patients, polymorphisms creating the three common apo E isoforms were associated
      with large effects on cholesterol, apo B and triglyceride levels (19.9%, 20.3%
      and 23.9% of sample variance) of similar magnitude as in the healthy individuals.
      Apo B polymorphisms were found to be associated with much smaller effects on
      lipid traits than in the healthy individuals. The only significant association
      was between the asparagine/serine4311 polymorphism and HDL-triglyceride levels.
      However, global severity of coronary atherosclerosis at the first angiography was
      found to be significantly associated with the LAL insertion/deletion polymorphism
      (P = 0.008). Thus variation at the apo B gene locus is associated with the
      development of atherosclerosis, but the data suggests that this may act through
      mechanisms not directly related to effects on measured lipid traits.

PMID- 1352975
TI  - The MspI restriction fragment length polymorphism 3' to the apolipoprotein A-II
      gene: relationships with lipids, apolipoproteins, and premature coronary artery
      disease.
AB  - In previous studies, a restriction fragment length polymorphism (RFLP) has been
      identified using MspI restriction endonuclease in the 3' region of the apo A-II
      gene. The rare variant site for this MspI (M2) has been reported to be associated
      with higher levels of HDL cholesterol and apo A-II. We have studied the frequency
      and lipid associations of this RFLP in a population of 168 coronary artery
      disease (CAD) male and female patients, who had more than 50% narrowing of one or
      more arteries prior to age 60 years, as well as 255 aged-matched males and
      females from the Framingham Offspring Study. We also studied 31 kindreds in which
      the proband had premature CAD. The frequency of the M2 allele was higher in CAD
      cases (0.20) than in the controls (0.13) (P less than 0.05). In general, those
      subjects carrying the M2 allele had lower HDL cholesterol and apo A-I plasma
      levels; however, this difference was only significant (P less than 0.02 and
      0.002, respectively) in females with CAD. No cosegregation of the M2 allele with
      hypoalphalipoproteinemia was found in 31 kindreds studied. However, in both
      generations there was a trend for those subjects carrying the M2 allele to have
      lower HDL cholesterol levels than those carrying the M1 allele. Sequence analysis
      of the apo A-II gene of subjects homozygous for either the M1 (n = 1) or the M2
      allele (n = 2) revealed that this RFLP is due to a T----C single base mutation
      528 bp 3' to the apo A-II gene. In the subjects homozygous for the M2 allele no
      other mutations were found within the coding region of the apo A-II gene that
      could result in changes in the primary sequence of the protein. These data
      indicate that the MspI RFLP 3' to the apo A-II gene is somewhat more frequent in
      the CAD group. However, there was no significant association between this RFLP
      and any of the parameters examined. In conclusion, this DNA marker lacks the
      specificity to be clinically useful for CAD risk assessment in the population
      studied.

PMID- 1352976
TI  - High density lipoproteins: physiopathology and clinical relevance.
AB  - On September 13-14 1991 a Symposium on High Density Lipoproteins: Physiopathology
      and Clinical Relevance was held in Bellagio (Italy). This Symposium was aimed at
      discussing various aspects of HDL from epidemiology to the most recent advances
      in the understanding of HDL metabolism and factors (diets, drugs) affecting their
      levels.

PMID- 1352977
TI  - The acute effects of a loading dose of phenylalanine in unipolar depressed
      patients with and without tardive dyskinesia.
AB  - The effects of a loading dose of 100 mg/kg phenylalanine (PHE) were assessed in
      three groups of DSM-III-R diagnosed unipolar depressed patients: patients with
      tardive dyskinesia (TD) (n = 11); patients exposed to neuroleptics (NLs) but
      without TD (n = 10); and patients never exposed to NLs (n = 10). No significant
      differences were obtained in fasting and 2 hour postloading PHE plasma levels
      between the groups. A statistically significant correlation was found between
      Abnormal Involuntary Movements Scale total scores and postloading PHE plasma
      levels (p less than .05). Three TD patients showed unusually large increases in
      PHE plasma levels and PHE:large neutral amino acid ratios. Abnormalities in PHE
      metabolism may contribute to the development and severity of TD in some NL
      treated unipolar depressed patients.

PMID- 1352978
TI  - Proceedings of the 6th US-USSR Symposium on Arterial Hypertension. Soviet Union,
      May 30-June 1, 1990.

PMID- 1352979
TI  - Management of essential hypertension in patients with different degrees of left
      ventricular hypertrophy. Multicenter trial.
AB  - Three hundred and four hypertensive patients with different degrees of left
      ventricular hypertrophy (LVH) were recruited and followed for 4 years. The
      patients were randomized into two groups: Group I (150 patients) was treated with
      a combination of hypotensive drugs including beta-blockers, and group II (154
      patients) was treated with the same combination of drugs including diuretics
      instead of beta-blockers. By the end of the fourth year, 60 endpoints were
      recorded: 17 strokes, 13 myocardial infarctions, and 30 cases of chronic coronary
      insufficiency. Mortality was statistically higher in group II (7 of 154 or 5% v 1
      of 150 or 1%) (P less than .035), but there was no difference between the groups
      in the incidence of nonfatal endpoints. These data confirm that beta-blockers can
      reduce mortality associated with the complications presented in hypertensive
      patients. Increased left ventricular myocardial mass (greater than 200 g,
      according to Teichholz' formula) was shown to have prognostic value for the
      development of complications. In patients with LVMM greater than 200 g, the
      probability of fatal complications was higher (P less than .007), as was the
      probability of nonfatal myocardial infarction (P less than .01), development of
      coronary artery disease (P less than .02), and all complications (P less than
      .0003). Regression of LVH to less than 200 g (according to Teichholz' formula)
      improved prognosis.

PMID- 1352980
TI  - B-HT 920 activates dopamine D2 receptors coupled to inhibition of adenylate
      cyclase activity.
AB  - In homogenates of female rat anterior pituitary, the azepine derivative B-HT 920
      inhibited the forskolin-stimulated adenylate cyclase activity with an EC50 value
      of 0.35 microM. In male rat anterior pituitary, B-HT 920 curtailed the
      stimulation of adenylate cyclase activity by vasoactive intestinal peptide with
      an EC50 of 0.20 microM. In synaptic plasma membranes of rat striatum, B-HT 920
      significantly reduced basal adenylate cyclase activity with an EC50 of 0.68
      microM. Both in pituitary and striatum, the B-HT 920 inhibition was counteracted
      by the dopamine (DA) D2 receptor antagonist 1-sulpiride, but not by the alpha 2
      adrenergic antagonist yohimbine. These results indicate that B-HT 920 is capable
      of activating DA D2 receptors negatively coupled to adenylate cyclase activity.

PMID- 1352981
TI  - Monitoring glutamine in mammalian cell cultures using an amperometric biosensor.
AB  - An amperometric biosensor has been developed for monitoring glutamine in the
      pulsed-batch cultivation of murine hybridoma cells. Glutamine oxidase was cross
      linked with bovine serum albumin (BSA) via glutaraldehyde activation and
      deposited on a preactivated nylon membrane. Glutaminase was then immobilized on
      the protein layer and the resulting membrane was attached to the sensing area of
      a hydrogen peroxide probe (platinum vs silver/silver chloride polarized at +0.7
      V). An orthogonal test was performed to optimize the activity of the membrane for
      glutamine with respect to the concentrations of glutamate oxidase, BSA,
      glutaminase and glutaraldehyde. There was an excellent linear relationship
      between the biosensor's response and glutamine in the range 0.1-3 mM. The
      determination of glutamine could be performed in 2 min and each membrane was
      reused for at least 300 consecutive analyses. The data obtained also agreed well
      with those high-performance liquid chromatography, thus validating the
      applicability of the biosensor.

PMID- 1352982
TI  - Metabotropic glutamate receptors are required for the induction of long-term
      potentiation.
AB  - Recent observations have led to the suggestion that the metabotropic glutamate
      receptor may play a role in the induction or maintenance of long-term
      potentiation (LTP). However, experimental evidence supporting a role for this
      receptor in the induction of LTP is still inconclusive and controversial. Here we
      report that, in rat dorsolateral septal nucleus (DLSN) neurons, which have the
      highest density of metabotropic receptors and show functional responses, the
      induction of LTP is not blocked by the NMDA receptor antagonist 2-amino-5
      phosphonovalerate, but is blocked by two putative metabotropic glutamate receptor
      antagonists, L-2-amino-3-phosphonopropionic acid and L-2-amino-4
      phosphonobutyrate. Furthermore, superfusion of (1S,3R)-1-aminocyclopentane-1,3
      dicarboxylic acid, a selective metabotropic glutamate agonist, resulted in a long
      lasting potentiation of synaptic transmission similar to that induced by tetanic
      stimuli. Our results demonstrated that activation of postsynaptic metabotropic
      receptors is both necessary and sufficient for the induction of LTP in the DLSN,
      and we suggest that such a mechanism may be important at other CNS synapses.

PMID- 1352983
TI  - The kinetics of the response to glutamate and kainate in neurons of the avian
      cochlear nucleus.
AB  - Neurons in the nucleus magnocellularis (nMAG) of the chicken precisely transmit
      auditory nerve activity via glutamatergic synapses. Using techniques for rapid
      application of solutions, we have explored the properties of CNQX-sensitive
      glutamate receptors in whole cells and outside-out patches from the nMAG.
      Glutamate-evoked current in patches desensitized biphasically to less than 1% of
      the peak current, with a fast time constant of 960 microseconds at 22 degrees C,
      decreasing to 570 microseconds at 33 degrees C. Dose-response studies using
      kainate indicated that at least two agonist molecules bind to gate the channel.
      We propose a kinetic model that quantitatively describes our experimental
      observations. The rapid kinetics of this receptor are well suited to allow phase
      locking of synaptic signals to auditory stimuli.

PMID- 1352984
TI  - Regional expression of three homeobox transcripts in the inner ear of zebrafish
      embryos.
AB  - The inner ear of all jawed vertebrates arises from the epithelium of the otic
      vesicle and contains three semicircular canals, otoliths, and sets of sensory
      neurons, all positioned precisely within the cranium to detect head orientation
      and movement. The msh-C gene and two new homebox genes, msh-D and a gene related
      to distal-less, dlx-3, are each expressed in distinct regions of the otic vesicle
      during its early development in zebrafish embryos. Cells in the ectoderm express
      dlx-3 before induction of the otic vesicle, suggesting that dlx-3 has an early
      function in this process. Later, cells aligned with the future axes of the
      semicircular canals specifically express either dlx-3 or msh-D. Even later,
      sensory hair cells express msh-C and msh-D, while other cells of the epithelium
      express dlx-3. The early expression of these genes could specify the orientation
      and morphogenesis of the inner ear, whereas their later expression could specify
      the fates of particular cell types.

PMID- 1352985
TI  - Tissue-specific transcription of the rat tyrosine hydroxylase gene requires
      synergy between an AP-1 motif and an overlapping E box-containing dyad.
AB  - Transcription of tyrosine hydroxylase (TH), the rate-limiting enzyme in
      catecholamine biosynthesis, is regulated in a tissue-specific manner. We have
      identified sequences from -205 to -182 as the minimal enhancer for TH in
      pheochromocytoma cells using site-directed mutagenesis. This segment
      (TGATTCAGAGGCAGGTGCCTGTGA) is composed of an AP-1 motif (TGATTCA) and an
      overlapping 20 bp dyad whose core resembles an E box site (CANNTG). Interaction
      between the two elements is necessary both in vivo and in vitro: mutation of
      either element caused a 65%-95% reduction in transcription, and the combination
      of the two elements conferred cell-specific activation on a heterologous
      promoter; separation of the two elements by an additional helical turn not only
      disrupted a DNA-protein complex unique to the two elements, but also abolished
      expression in vivo. Therefore, we conclude that the interaction between the AP-1
      and the E box dyad motifs is responsible for cell-specific TH expression.

PMID- 1352986
TI  - A new Conus peptide ligand for mammalian presynaptic Ca2+ channels.
AB  - Voltage-sensitive Ca2+ channels that control neurotransmitter release are blocked
      by omega-conotoxin (omega-CgTx) GVIA from the marine snail Conus geographus, the
      most widely used inhibitor of neurotransmitter release. However, many mammalian
      synapses are omega-CgTx-GVIA insensitive. We describe a new Conus peptide, omega
      CgTx-MVIIC, that is an effective inhibitor of omega-CgTx-GVIA-resistant synaptic
      transmission. Ca2+ channel targets that are inhibited by omega-CgTx-MVIIC but not
      by omega-CgTx-GVIA include those mediating depolarization-induced 45Ca2+ uptake
      in rat synaptosome preparations, "P" currents in cerebellar Purkinje cells, and a
      subset of omega-CgTx-GVIA-resistant currents in CA1 hippocampal pyramidal cells.
      The characterization of omega-CgTx-MVIIC by a combination of molecular genetics
      and chemical synthesis defines a general approach for obtaining ligands with
      novel receptor subtype specificity from Conus.

PMID- 1352987
TI  - Sympathetic neurons mediate developmental change in cardiac sodium channel gating
      through long-term neurotransmitter action.
AB  - Innervation of nerve and muscle cells during development is often accompanied by
      changes in the expression and function of ion channels in the postsynaptic cell.
      However, the signaling pathways whereby the presynaptic nerve influences the
      properties of the postsynaptic cell are less well understood. Indirect evidence
      suggests that cardiac voltage-gated Na+ channels undergo important changes during
      development. Here, we compare directly single voltage-gated Na+ channel currents
      from neonatal and adult rat ventricular myocytes and report a negative shift in
      the voltage dependence of channel gating during development, leading to a
      significant speeding of channel activation and inactivation at a fixed membrane
      potential. These developmental changes can be mimicked in vitro by innervation of
      neonatal myocytes with sympathetic neurons. The effect of sympathetic neurons is
      blocked by the beta-adrenergic receptor antagonist propranolol and is mimicked by
      prolonged coculture of neonatal myocytes with a membrane-permeable cAMP analog.
      Thus presynaptic neurons can control the developmental phenotype of ion channels
      in a postsynaptic cell through a classic receptor-mediated neurotransmitter
      action that involves a defined second messenger pathway.

PMID- 1352988
TI  - Impairment of carbamazepine-10, 11-epoxide elimination by valnoctamide, a
      valpromide isomer, in healthy subjects.
AB  - The effect of the valpromide isomer valnoctamide (VCD, 200 mg three times daily
      for 8 days), an over-the-counter tranquillizer, on the elimination kinetics of a
      single oral dose of carbamazepine-10, 11-epoxide (CBZ-E, 100 mg) was investigated
      in healthy subjects. During VCD treatment, the half-life of CBZ-E was prolonged
      significantly compared with control (19.7 +/- 6.7 h vs 6.9 +/- 2.0 h, means +/-
      s.d., P less than 0.01), and its oral clearance decreased four-fold (from 109.6
      +/- 30.7 to 28.8 +/- 11.1 ml h-1 kg-1, P less than 0.01). These findings indicate
      that VCM, like valpromide, strongly inhibits epoxide hydrolase in vivo.

PMID- 1352989
TI  - Extracellular calcium mimics the actions of platelet-derived growth factor on
      mouse fibroblasts.
AB  - Microprecipitates of calcium phosphate (CaPO4) can substitute for platelet
      derived growth factor (PDGF) to stimulate the growth of cultured 3T3 cells. In
      two-part complementation assays, CaPO4 behaves as a PDGF-like "competence factor"
      -that is, the mitogenic response to CaPO4 is enhanced synergistically by
      "progression factors" contained in platelet-poor plasma. In studies described
      here, we show that early cytoplasmic and intranuclear events in the mitogenic
      response to CaPO4 are equivalent to those induced by PDGF. However, no net
      increase in tyrosine kinase activity of either the PDGF-alpha or PDGF-beta
      receptor is seen following exposure to CaPO4. Our data suggest that calcium acts
      within the cell, regulating events which normally proceed from activation of PDGF
      receptors. Alternatively, microprecipitates of CaPO4 could act externally by
      activating a growth factor receptor which escapes detection with available
      reagents.

PMID- 1352991
TI  - 7th European BioEnergetics Conference (EBEC). Helsinki, Finland, 26-31 July,
      1992.

PMID- 1352990
TI  - Modulation of P-glycoprotein phosphorylation and drug transport by sodium
      butyrate.
AB  - P-Glycoprotein (Pgp) expression in cell lines derived from tumors arising from
      cells which normally express Pgp can be increased by sodium butyrate and other
      differentiating agents. Although the Pgp level increased 25-fold after sodium
      butyrate treatment in SW620 human colon carcinoma cells, the intracellular
      accumulation of vinblastine, adriamycin, and actinomycin D increased rather than
      decreased. In contrast, colchicine showed the expected decrease in accumulation,
      as a result of increased efflux. Likewise, treatment of a Pgp-expressing
      multidrug-resistant SW620 subline with sodium butyrate resulted in active
      interference with Pgp function. This effect was partially reversed by phorbol
      esters with a resulting decrease in the accumulation of vinblastine, adriamycin,
      and actinomycin D. Sodium butyrate, while increasing Pgp levels, inhibited the
      phosphorylation of Pgp. Time course studies revealed a tight relationship between
      decreased Pgp phosphorylation and increased vinblastine accumulation after sodium
      butyrate treatment. Either treatment with phorbol esters or withdrawal of sodium
      butyrate increased Pgp phosphorylation while decreasing vinblastine accumulation.
      These studies suggest that the specificity of Pgp transport can be modulated by
      phosphorylation and that vinblastine, adriamycin, or actinomycin D transport, but
      not that of colchicine, is diminished after dephosphorylation by sodium butyrate.

PMID- 1352992
TI  - A bioenergetic approach to the nerve terminal.

PMID- 1352993
TI  - Proteolytic processing of human lysosomal arylsulfatase A.
AB  - Arylsulfatase A purified from human placenta contained an unreported component
      with an apparent molecular mass of 7 kDa in addition to the two known components
      with apparent molecular masses of 58 and 50 kDa. The detailed relationship
      between the 58 kDa component and the 50 kDa component is as yet unknown. The
      present study was undertaken to define the structure of the subunits of the
      sulfatase. The N-terminal sequence of the 50 kDa component was identical to that
      of the 58 kDa component. Furthermore, the peptide maps of the 50 kDa component,
      which was separately digested with trypsin and Achromobacter proteinase I, were
      quite similar to those of the 58 kDa one. Through sequence analysis of the
      incompatible peaks in the peptide maps, the 50 kDa component was found to lack a
      sequence from Val-445 to the C-terminus. On the other hand, the N-terminal
      sequence of the 7 kDa component began with Ala-448, though there was a minor
      sequence commencing with Thr-449. These observations suggest that the 50 and 7
      kDa components were produced by limited proteolysis near the C-terminus of the 58
      kDa component. Through analysis using unreducing SDS-PAGE, the 58 and the 7 kDa
      components were found to be linked by disulphide bonds. Arylsulfatase A purified
      from human liver was also composed of the same subunits as the placental one.
      This finding suggests that human arylsulfatase A undergoes similar proteolytic
      processing regardless of the tissue involved.

PMID- 1352994
TI  - MK-801 selectively protects mouse arcuate neurons in vivo against glutamate
      toxicity.
AB  - The receptor mediating glutamate toxicity in vivo has not yet been identified.
      The effects of NMDA antagonist MK-801 and the AMPA antagonist NBQX were studied
      on glutamate toxicity in the arcuate nucleus of newborn and adult mice.
      Morphometric methods were used to determine the effects of antagonists on
      glutamate toxicity. In the developing arcuate, MK-801 abolished glutamate
      neurotoxicity whereas NBQX has no effect. MK-801, but not NBQX, afforded
      significant but not complete protection in mature arcuate neurons. The residual
      toxicity could not be blocked by co-administration of NBQX which paradoxically
      partially inhibited the protective effect of MK-801. The results show that
      throughout development, glutamate neurotoxicity in the arcuate nucleus is
      predominantly mediated by NMDA receptors.

PMID- 1352995
TI  - Glutamate receptors mediate acoustic input to the reticular brain stem.
AB  - Previous studies have shown that many neurons of the pontine reticular brain stem
      respond to acoustic stimulation. However, it was not clear which neurotransmitter
      is involved in the mediation of auditory information. As glutamate appears to be
      a prominent transmitter in the auditory system, we iontophoretically applied
      antagonists of the AMPA/kainate- and NMDA-receptors to reticular neurons. Both
      glutamate antagonists reduced the acoustically evoked response, with the
      AMPA/kainate-receptor antagonist being more efficient. As the neurons showed a
      short latency and a high intensity threshold to the acoustic stimuli and most of
      them appeared to project into the spinal cord, we conclude that glutamate
      receptors on reticulospinal pontine brain stem neurons probably mediate auditory
      short-latency behaviour, such as the startle response.

PMID- 1352996
TI  - Nucleotide sequence of a gene from Phanerochaete chrysosporium that shows
      homology to the facA gene of Aspergillus nidulans.
AB  - Heterologous hybridisation was used to isolate a genomic DNA sequence from
      Phanerochaete chrysosporium using the facA (acetyl CoA synthetase) gene from
      Aspergillus nidulans as a probe. The cloned sequence hybridises to a 2.2 kb
      transcript in poly(A)+ RNA prepared from mycelium grown on acetate as the sole
      carbon source. Comparison of the DNA sequence obtained with those of the A.
      nidulans facA and N. crassa acu5 genes reveals an ORF that appears to be
      interrupted by five typical fungal introns. Two possible candidates for the
      translation initiation codon were observed. Homology with the facA and acu5 genes
      is revealed after the second ATG codon.

PMID- 1352997
TI  - Bronchodilator-resistive cough in atopic patients: bronchial reversibility and
      hyperresponsiveness.
AB  - The number of atopic patients presenting only chronic non-productive cough
      appears to be increasing. This study was conducted to confirm the existence of
      non-asthmatic cough associated with atopy. We prospectively examined atopic
      findings, therapeutic effects of inhaled procaterol, azelastin, and/or
      glucocorticoids, improvement of FEV1 by bronchodilator therapy and bronchial
      responsiveness to methacholine in 20 patients. The cough was relieved by inhaled
      procaterol in 10 patients (Group 2) but not in the other 10 patients (Group 1).
      The increase in FEV1 by inhaled salbutamol following aminophylline injection was
      significantly less in Group 1 than in Group 2. Bronchial responsiveness to
      methacholine was normal in Group 1 while that in Group 2 was hyperreactive. These
      findings indicate that there is atopic non-asthmatic bronchodilator-resistive
      cough (Group 1) which is a different entity from bronchodilator-responsive cough
      (Group 2), or the so-called "cough variant asthma".

PMID- 1352998
TI  - Unilateral facial swelling and exophthalmos in a patient with polyarteritis
      nodosa.
AB  - A patient with polyarteritis nodosa (PN) presenting with exophthalmos and facial
      swelling, which are rarely found in PN, is reported. The patient, a 27-year-old
      male, complained of painful facial swelling and diplopia. Physical examinations
      showed facial swelling around the right orbit and exophthalmos. After admission,
      he experienced myalgia in both calves. Laboratory studies disclosed leukocytosis
      and liver dysfunction. Celiac and renal angiograms showed aneurysms. A biopsy
      specimen of his left calf showed an arterial inflammatory process. The patient
      was diagnosed as having PN. He had an excellent response to corticosteroids, with
      prompt improvement.

PMID- 1352999
TI  - CSF corticotropin-releasing hormone and somatostatin in major depression:
      response to antidepressant treatment and relapse.
AB  - Immunoreactive corticotropin-releasing hormone (CRH) and somatostatin (SRIF) were
      measured in the cerebrospinal fluid (CSF) of 24 female in-patients, suffering
      from DSM-III-R major depression, both before and after antidepressant treatment.
      In the total group there were no significant differences between pre- and post
      treatment CSF-CRH and SRIF concentrations despite satisfactory clinical
      improvement in each patient. However, there was a significant post-treatment
      reduction of the CSF-CRH concentration in the 15 patients who remained depression
      free for at least 6 months following treatment, in contrast to the tendency for
      elevation in those 9 subjects who relapsed within 6 months. CSF-SRIF showed no
      similar pattern. High, or even increasing, CSF-CRH concentration during
      antidepressant treatment may indicate lack of normalization of an underlying
      process in major depression despite symptomatic improvement and predicted early
      relapse.

PMID- 1353000
TI  - Additive effects of chronic treatment with antidepressant drugs and intermittent
      treatment with a dopamine agonist.
AB  - Locomotor activity in response to the D2/D3 agonist quinpirole was studied in
      male rats treated chronically (25-40 days) with imipramine, amitriptyline or
      mianserin (5 mg/kg/day). All three antidepressants potentiated the response to
      quinpirole. Repeated administration of quinpirole at 3-day intervals also caused
      a marked increase in the locomotor response to quinpirole. Imipramine-treated
      animals were more active than vehicle-treated animals on all quinpirole trials.
      Animals tested in the locomotor activity apparatus for the first time following
      their fifth quinpirole injection showed sensitization, but to a lesser extent
      than animals tested repeatedly under quinpirole. This context-independent
      sensitization was potentiated by all three antidepressants. We discuss the
      potential clinical relevance of these results.

PMID- 1353002
TI  - Impact of neuropharmacology in the 1990s--treatment strategies for anxiety
      disorders and insomnia. Task Force of the Collegium Internationale Neuro
      Psychopharmacologicum (CINP).

PMID- 1353001
TI  - Sigma receptor modulation of the muscle relaxant action of eperisone.
AB  - We examined the mechanism of the muscle relaxant action of eperisone, using
      Straub tail and binding studies. In vivo, eperisone (50 and 100 mg/kg i.p.)
      produced a dose-dependent inhibition of the Straub tail in mice and this
      inhibitory effect was significantly reversed by haloperidol (0.5 mg/kg i.p.).
      This drug in itself had no effect on the Straub tail. Sulpiride (50 mg/kg i.p.)
      failed to reverse the inhibitory effect of eperisone. In vitro, (+)-3-(3
      [3H]hydroxyphenyl)-N-(1-propylpiperidine) ((+)-[3H]3-PPP) specific binding, in
      rat brain membrane, was prevented by eperisone and the IC50 value was 0.43 nM.
      The muscle relaxant action of eperisone may be modulated by sigma receptors.

PMID- 1353004
TI  - Nonoperative treatment of neurosurgical infections.
AB  - The indications for nonsurgical management of CNS infections manifested by
      collections of pus are very limited. In general, such management is restricted to
      neurologically intact patients who are unable to undergo the needed surgical
      procedure and in whom the organism can be identified presumptively from other
      cultures. In such circumstances, brain abscesses less than 1.5 cm in diameter,
      small subdural empyemas, some spinal epidural abscesses, and many cases of spinal
      osteomyelitis can be successfully treated with prolonged intravenous antibiotic
      therapy. In patients who are unable to tolerate a neurosurgical procedure, the
      presence of an infectious CNS mass lesion is not hopeless and vigorous medical
      therapy offers the possibility of cure.

PMID- 1353005
TI  - Infections of the dural spaces.
AB  - Suppuration involving the epidural and subdural spaces is a rare occurrence in
      modern neurosurgical practice. Early diagnosis and appropriate treatment of
      infections of the dural spaces may avert the high incidence of neurologic
      disability and death traditionally associated with them, however. Prompt
      neurosurgical intervention in the treatment of these lesions has been the
      standard with which all other therapies have been compared.

PMID- 1353003
TI  - Mouse F9 teratocarcinoma stem cells expressing the stably transfected homeobox
      gene Hox 1.6 exhibit an altered morphology.
AB  - Expression of the murine homeobox gene Hox 1.6 rapidly increases in F9
      teratocarcinoma cells when these cells are induced with retinoic acid to
      differentiate into primitive and parietal endoderm. Hox 1.6 encodes a putative
      transcriptional regulatory protein which may function as a secondary regulator of
      gene expression during the differentiation process. To examine the role of the
      Hox 1.6 gene, we have stably transfected F9 stem cells with a cDNA containing the
      complete coding sequence of Hox 1.6 under the control of the mouse
      metallothionein promoter. Two clonally distinct cell lines that express high
      levels of the transfected Hox 1.6 gene have been isolated and characterized. We
      show that expression of the transfected Hox 1.6 gene in F9 cells dramatically
      alters the stem cell morphology. However, the transfected cells do not
      differentiate in the absence of retinoic acid treatment, nor are they prevented
      from differentiating in response to such treatments. We therefore suggest that
      the Hox 1.6 gene controls the expression of genes which influence changes in F9
      cell morphology during RA-induced differentiation.

PMID- 1353006
TI  - Peripheral blood stem cell transplantation.
AB  - Haematopoietic stem cells are usually sessile within the bone marrow
      microenvironment. However, small numbers do circulate in the peripheral blood of
      normal individuals, and following chemotherapy and/or intravenous growth factors,
      a substantial transient rise in circulating stem cells occurs. Leukocytes
      harvested by cytapheresis at this time can be used for autologous reconstitution
      of the haematopoietic and lymphoid systems following high dosage
      chemo/radiotherapy for the treatment of malignant disease. Peripheral blood stem
      cell transplants give rise to similar disease response rates as autologous bone
      marrow transplants, but have the advantage of more rapid haematopoietic
      reconstitution, and in addition can be offered to patients in whom marrow harvest
      is not feasible due to bone marrow damage or infiltration. This article reviews
      the theoretical and historical background to haematopoietic stem cell research,
      current clinical practice in peripheral blood stem cell mobilisation and
      harvesting, addresses the potential advantages and disadvantages compared to bone
      marrow transplantation, and assesses current experience of comparative efficacy.

PMID- 1353007
TI  - A microcomputer FORTRAN program for rapid determination of lethal concentrations
      of biocides in mosquito control.
AB  - Probit analysis calculations are highly useful in biology and related sciences.
      Since the statistical calculations and tests required are quite involved, the use
      of an automatic computer program is desirable. The description of the
      computational procedures and use of the computer program with suitable examples
      from mosquito control programmes are discussed.

PMID- 1353008
TI  - Homozygosity for the transthyretin-Met30-gene in seven individuals with familial
      amyloidosis with polyneuropathy detected by restriction enzyme analysis of
      amplified genomic DNA sequences.
AB  - Familial amyloidotic polyneuropathy (FAP) with a mutation in position 30 of
      transthyretin (TTR) (previously called prealbumin) is an autosomal dominant
      inherited disorder characterized by varying degrees of peripheral neuropathy,
      nephropathy, gastrointestinal problems, and vitreous amyloid. We have earlier
      diagnosed homozygosity for the TTR-Met30-gene using Southern analysis in four
      Swedish individuals. We have found it possible to detect homozygosity for the Met
      30 mutation by amplifying discrete regions of the TTR-gene using polymerase chain
      reaction (PCR), and the amplification products restricted with NsiI analysed by
      gel electrophoresis. Clinical data on seven homozygous individuals, including
      three new cases, are presented.

PMID- 1353009
TI  - Pregnancy and its effect on HIV/AIDS.

PMID- 1353010
TI  - Cranial nerve involvement in childhood polyarteritis nodosa.
AB  - Amongst a variety of neurological manifestations of childhood polyarteritis
      nodosa, cranial nerve involvement is unusual. We report 4 cases with cranial
      nerve palsies in a series of 36 biopsy-proven patients. Two cases presented with
      IIIrd nerve palsy alone, one with right IIIrd and left IVth nerve palsy, and one
      with peripheral VIIth nerve paresis. All 4 patients showed good response to
      prednisolone and cyclophosphamide treatment. Cranial nerve involvement in
      childhood polyarteritis nodosa seems not so rare when patients are followed on
      long term basis.

PMID- 1353011
TI  - Chronic treatment with L-threonine in amyotrophic lateral sclerosis: a pilot
      study.
AB  - Thirty patients suffering from amyotrophic lateral sclerosis were included in an
      open therapeutical trial. They were randomized to receive either L-threonine
      (Thr), a precursor of the inhibitory amino acid glycine, or vitamin B or
      carnitine. Thirteen patients (9 patients on Thr and 4 control subjects) completed
      the 1-year trial. No statistical differences were observed between the treated
      group and the control patients in the decline of the clinical assessment score.
      Nevertheless, Thr-treated patients complained less frequently of respiratory
      failure than the control group despite bulbar involvement being more common in
      the Thr group at entry.

PMID- 1353012
TI  - Reconstruction of the burned foot.
AB  - Burns of the feet pose unique and difficult problems in initial management,
      reconstruction, and the attainment of long-term functional results. The primary
      reconstructive goals for this region are unimpeded ambulation and weightbearing.
      These objectives can be achieved by adherence to established principles of wound
      management, a clear delineation of the reconstructive requirements of the foot,
      and a team approach toward attaining these goals.

PMID- 1353013
TI  - Polycystic kidney disease. International workshop.

PMID- 1353015
TI  - 58th Annual International Scientific Assembly. Chicago, October 25-29, 1992.
      Abstracts.

PMID- 1353016
TI  - Effect of ionic strength in immunocytochemical detection of the proliferation
      associated nuclear antigens p120, PCNA, and the protein reacting with Ki-67
      antibody.
AB  - This study was aimed at revealing whether or not ionic interactions between the
      epitope of the antigen detected by Ki-67 antibody, or the proliferation
      associated proteins PCNA or p120, and neighboring cellular constituents impede
      detectability of these antigens in HL-60 cells by indirect immunofluorescence
      assay. To this end, the ionic strength (NaCl concentration) of the solutions in
      which cells were suspended during their fixation with 0.5% paraformaldehyde was
      increased, to up to 1.65 M NaCl, to weaken the intra- and/or intermolecular ionic
      interactions during the process of crosslinking, and the cells were then
      immunostained. Fluorescence of cells reacting with Ki-67 antibody was maximally
      increased after their treatment with 1.15 M NaCl; the average increase was nearly
      110% above the level seen with the standard methodology utilizing 0.15 M NaCl.
      The increase was greater for cells in the G1 phase of the cell cycle compared to
      cells in S or G2. Fluorescence of cells stained with the PCNA antibody was
      maximally enhanced after cell treatment with 0.65 M NaCl. The enhancement,
      however, varied depending on the source of the antibody; it was nearly 200% in
      the case of the antibody provided by Boehringer and over 100% by DAKO. Detection
      of the nucleolar antigen p120 was not significantly affected by 0.65-1.65 M NaCl.
      The data indicate that ionic interactions between cellular constituents indeed
      play a role in masking the epitope of PCNA and the antigen detected by Ki
      67.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353014
TI  - Zuclopenthixol, melperone and haloperidol/levomepromazine in the elderly. Meta
      analysis of two double-blind trials at 15 nursing homes in Norway.
AB  - A meta-analysis was carried out of the data from two double-blind, multi-centre
      studies with identical methodology which compared the effectiveness of treatment
      of elderly patients with zuclopenthixol and with other antipsychotic drugs. In
      one study, patients were treated for 4 weeks with either zuclopenthixol or
      melperone; in the other, with either zuclopenthixol or a combination of
      haloperidol and levomepromazine. The meta-analysis evaluated the results of 96
      patients, 49 in the zuclopenthixol group and 47 in the comparison group. Doses,
      which were adjusted to individual patient's needs, were low as shown by the
      percentages of defined daily doses for each of the study drugs. The results
      indicated that all three treatment alternatives were effective in the treatment
      of elderly patients with symptoms of agitation and hostility/aggressiveness.
      There was a trend, however, for zuclopenthixol to have a more rapid onset of
      effect. Zuclopenthixol also has the advantage for both patients and nursing staff
      that dosage is once daily. Only few and mild side-effects were reported with the
      three drug regimens.

PMID- 1353017
TI  - The intravenous self-administration of antihistamines by rhesus monkeys.
AB  - Rhesus monkeys were trained to lever press for infusions of cocaine during daily,
      1-h experimental sessions. Following stabilization of the cocaine-maintained
      baselines, various antihistamines were substituted for cocaine to determine
      whether they would be self-administered. The results indicated that all monkeys
      tested self-administered tripelennamine and chlorpheniramine. One monkey out of
      the four self-administered pyrilamine, but only at a single (300 microgram/kg)
      high dose. Phenyltoloxamine, cimetidine and hydroxyzine were not self
      administered. These results further illuminate differences amongst H1 antagonists
      in their potential for self-administration and, when examined in context with
      other reports, suggest that stimulant-like properties may help mediate their
      reinforcing effects when present.

PMID- 1353018
TI  - Proceedings of the 8th International Symposium on Endoscopic Ultrasonography.
      Munich, June 15, 1991.

PMID- 1353019
TI  - Endoscopic ultrasonography in the preoperative localization of pancreatic
      endocrine tumors.

PMID- 1353020
TI  - Kinetics of daunorubicin transport by P-glycoprotein of intact cancer cells.
AB  - Drug permeation across the plasma membrane of multidrug-resistant cells depends
      on the kinetics of the P-glycoprotein-mediated pump activity as well as on the
      passive permeation of the drug. We here demonstrate a method to characterize
      kinetically the pump in intact cells. To this purpose, we examined the membrane
      transport properties of daunorubicin in various sensitive cancer cell lines and
      in their multidrug resistant (MDR) counterparts. First, we determined the passive
      permeability coefficient for daunorubicin. Then, using a flow-through system, the
      drug flux into the cell was measured after inhibition of the P-glycoprotein
      mediated efflux pump. Combining the two results allowed us to calculate the
      intracellular free concentration of the drug. In the steady-state, the pump rate
      must equal the net rate of passive diffusion of the drug and, therefore, the same
      experiments gave us the pumping rate of daunorubicin. These experiments were then
      repeated at various extracellular drug concentrations. By plotting the pumping
      rate versus the intracellular drug concentration, we then characterized the P
      glycoprotein kinetically. Four independent methods were used to measure the
      passive permeability coefficient for the cell line A2780. Similar values were
      obtained. Maximal pump rates (Vmax) showed a good correlation with the amount of
      P-glycoprotein in the cell lines used. We obtained saturation curves for the
      variation of the pump rates with the intracellular daunorubicin concentrations.
      These curves were typical for positive cooperativity, which provides evidence
      that at least two binding sites for daunorubicin are present on the active
      transport system of daunorubicin. The apparent Km values for P-glycoprotein
      mediated transport, the intracellular free cytosolic daunorubicin concentrations
      at half-maximal velocity for the cell lines used, were approximately 1.5 microM.
      Except for the cell lines with the highest amount of P-glycoprotein, the passive
      efflux rate of daunorubicin proved to be a substantial part of the total
      daunorubicin efflux rate for the cell lines used. In cell lines with relatively
      low levels of P-glycoprotein, passive daunorubicin efflux was even the main route
      of daunorubicin transport from the cells, determining the intracellular steady
      state concentrations of daunorubicin.

PMID- 1353021
TI  - XIVth Congress of the European Society of Cardiology. Barcelona, Spain, 30 August
      3 September 1992. Abstracts.

PMID- 1353022
TI  - A TaqI polymorphism in the human interleukin-1 beta (IL-1 beta) gene correlates
      with IL-1 beta secretion in vitro.
AB  - In the present study we searched for restriction fragment length polymorphisms
      (RFLP) in the human interleukin-1 beta (IL-1 beta) gene and for correlations to
      monocyte (Mo) function in non-related healthy donors and insulin-dependent
      diabetic patients. We demonstrated a diallelic polymorphism with the restriction
      enzyme TaqI consisting of fragments of 9.4 kb and 13.4 kb. No differences in
      allele or genotype frequencies of this RFLP were observed between randomly
      selected controls and randomly selected patients with insulin-dependent diabetes
      mellitus (IDDM). However, when analysing IDDM patients negative for HLA-DR3 and 
      DR4, our data demonstrate that the 13.4 kb allele is more frequent in this group
      compared to a matched control group. The functional impact of this RFLP was
      studied by analysing in vitro stimulated Mo IL-1 beta response. An IL-1 beta
      allele dosage effect on secretory capacity was observed after LPS-stimulation:
      13.4/13.4 kb homozygous individuals secreted significantly more IL-1 beta than
      9.4/13.4 kb heterozygous individuals, who secreted significantly more than
      9.4/9.4 kb homozygous individuals. Analyses of supernatants from LPS-stimulated
      Mo cultures from individuals with each TaqI IL-1 beta genotype revealed no
      differences in the mouse thymocyte co-stimulatory assay when compared on a molar
      basis, indicating that the TaqI polymorphism gave rise only to quantitative
      differences in expression levels and probably not to a mutant IL-1 beta.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1353023
TI  - Mechanism of catalysis of Fe(II) oxidation by ferritin H chains.
AB  - Recombinant H chain ferritins bearing site-directed amino acid substitutions at
      their ferroxidase centres have been used to study the mechanism of catalysis of
      Fe(II) oxidation by this protein. UV-difference spectra have been obtained at
      various times after the aerobic addition of Fe(II) to the recombinants. These
      indicate that the first product of Fe(II) oxidation by wild type H chain
      apoferritin is an Fe(III) mu-oxo-bridged dimer. This suggests that fast oxidation
      is achieved by 2-electron transfer from two Fe(II) to dioxygen. Modelling of
      Fe(III) dimer binding to human H chain apoferritin shows a solvent-accessible
      site, which resembles that of ribonucleotide reductase in its ligands.
      Substitution of these ligands by other amino acids usually prevents dimer
      formation and leads to greatly reduced Fe(II) oxidation rates.

PMID- 1353024
TI  - Nucleotide sequence of a cDNA encoding human tumor necrosis factor beta from B
      lymphoblastoid cell RPMI 1788.
AB  - Published sequences of cDNA for human tumor necrosis factor beta (TNF-beta) have
      a discrepancy within the coding region as well as exon 1. To resolve these
      discrepancies we have re-isolated TNF-beta cDNA from the human B cell
      lymphoblastoid cell line, RPMI 1788, and determined its DNA sequence. Results
      indicate that amino acid 26 is threonine (Thr) instead of asparagine (Asn). In
      contrast to published sequences, the sequence of the exon 1 region corresponded
      to the genomic sequence of TNF-beta. From our studies we conclude that the TNF
      beta gene of the human B cell lymphoblastoid cell line, RPMI 1788, is homologous
      with respect to the TNF-beta gene.

PMID- 1353025
TI  - Formation and quantification of protein complexes between peroxisomal alcohol
      oxidase and GroEL.
AB  - We have studied the use of yeast peroxisomal alcohol oxidase (AO) as a model
      protein for in vitro binding by GroEL. Dilution of denatured AO in neutral buffer
      leads to aggregation of the protein, which is prevented by the addition of GroEL.
      Formation of complexes between GroEL and denatured AO was demonstrated by a gel
      shift assay using non-denaturing polyacrylamide gel electrophoresis, and
      quantified by laser-densitometry of the gels. In the presence of MgAMP-PNP or
      MgADP the affinity of GroEL for AO was enhanced. Under these conditions up to 70%
      of the purified GroEL formed a complex with this protein. Release was stimulated
      at room temperature by MgATP, and was further enhanced by addition of GroES.

PMID- 1353026
TI  - Characterization of the pcp gene encoding the pyrrolidone carboxyl peptidase of
      Bacillus subtilis.
AB  - Pyrrolidone carboxyl peptidase (EC 3.4.11.8) (Pcp) is an enzyme that catalyzes
      the removal of the N-terminal pyroglutamyl group from some peptides or proteins.
      Its value in protein chemistry and bacterial diagnosis makes this enzyme an
      interesting subject of study. The present paper reports for the first time the
      cloning and characterization of a pyrrolidone carboxyl peptidase gene (pcp). This
      gene is present in a single copy in the genome of Bacillus subtilis as indicated
      by Southern blot hybridization analysis. The pcp transcripts were analyzed in
      Escherichia coli by Northern blot hybridization and S1 nuclease mapping. The
      deduced amino acid sequence predicts a protein of 215 amino acids with a
      calculated molecular weight of 23,777 Da. The pcp gene has been over-expressed in
      E. coli, allowing the identification and partial characterization of Pcp protein.

PMID- 1353027
TI  - Computational approach towards the three-dimensional structure of E. coli
      tyrosine aminotransferase.
AB  - We present a new model for E. coli tyrosine aminotransferase based on the X-ray
      structures of the wild type and Val39Leu mutant of E. coli aspartate
      aminotransferase and computer simulation studies. Active site characteristics of
      the model are correlated with experimental observations on the specificity of
      these enzymes towards aromatic/dicarboxylic acid substrates.

PMID- 1353029
TI  - [The TSH receptor gene and the pathogenesis of Graves' disease].
AB  - The molecular cloning of the thyrotropin (TSH) receptor cDNA has led to advances
      in understanding the structure and function of the molecule and the pathogenesis
      of autoimmune thyroid disease. The recombinant TSH receptors expressed on
      mammalian cells are now available for TSAb and TBIAb assays. TBI assay in this
      system is much more sensitive than the conventional method. The binding sites for
      TSH and TSAb/TBIAb have been studied with epitope library, synthetic peptides,
      anti-peptide sera and mutagenesis. Some of these data, however, are confusing and
      undefined. The binding sites for TSH and TSAb/TBIAb are very likely to span the
      entire region of the extracellular domain of the TSH receptor with discontinuous
      contact points, and seem to be different from each other on N-terminal half, but
      similar on C-terminal half, of the extracellular domain of the receptor. However,
      the determination of the precise amino acids involved may be very difficult
      without monoclonal anti-TSH receptor antibodies.

PMID- 1353028
TI  - The effect of two dopaminergic drugs on menstrual function and psychological
      state in hyperprolactinemia.
AB  - OBJECTIVE: To investigate the effect of dopaminergic drugs on the well being in
      hyperprolactinemic patients. DESIGN: A psychometric test for well being, the SCL
      90, was applied at baseline and in the 24th week of a double-blind randomized
      prospective study comparing the effectiveness and safety of the new dopamine d2
      agonist CV 205-502 with bromocriptine. SETTING: Outpatient department of a
      university clinic for obstetrics and gynecology. PATIENTS: Twenty-four women with
      hyperprolactinemia, 9 of whom had a prolactinoma. Twenty had been treated before,
      and 11 were known to react unfavorably to bromocriptine. RESULTS: The
      effectiveness of CV 205-502 was identical to bromocriptine: its tolerability
      appeared to be better, especially in the initial phase of treatment. At baseline,
      the mean scores of the SCL-90 were significantly elevated over the reference
      values. Sixteen patients had normal scores. The elevations were caused by 8
      patients with scores in the range found in psychiatric disease (211 +/- 30 [SD]
      [CV 205-502] and 182 +/- 32 [bromocriptine]). They were depressed, anxious, and
      hostile. At 24 weeks, the patients treated with CV 205-502 scored better (130 +/-
      23.5) in the SCL-90 than the patients treated with bromocriptine (149.5 +/- 20).
      CONCLUSION: The markedly increased well being in patients treated with CV 205-502
      cannot be explained by its better tolerability and is probably caused by a
      specific central activity of CV 205-502. Further research into the antidepressive
      properties of this compound is warranted.

PMID- 1353030
TI  - Non-alpha 2-adrenoceptor idazoxan binding sites; a new target for drug
      development.

PMID- 1353032
TI  - The MboI polymorphism at codon 192 of the human tyrosinase gene is present in
      Asians and Afrocaribbeans.

PMID- 1353031
TI  - Post-thymic T cell development in rats: an update.

PMID- 1353033
TI  - In vitro modelling of a mechanism of drug-related hypersensitivity.

PMID- 1353034
TI  - The modification of bovine beta-casein using transglutaminase purified from
      guinea pig liver.

PMID- 1353035
TI  - Identification of a novel particulate pyroglutamate aminopeptidase from bovine
      brain.

PMID- 1353036
TI  - Analysis of the mechanism of resistance of 7 novel MDR variants.

PMID- 1353037
TI  - Preliminary studies of a monoclonal antibody raised to the over expressed plasma
      membrane associated glycoprotein of a multidrug resistant cell line.

PMID- 1353038
TI  - Molecular cloning approach for a putative ethylene receptor gene in Arabidopsis.

PMID- 1353039
TI  - Measurement of erbB-2 oncoprotein in human breast cancers by ELISA.

PMID- 1353041
TI  - Expression of drug-metabolizing enzymes and P-170 glycoprotein in colorectal
      carcinoma and normal mucosa.
AB  - Resistance to chemotherapy is a significant problem in the treatment of
      colorectal carcinomas. To obtain insight into the mechanism of drug resistance,
      the expression of P-170 glycoprotein and biotransformation enzymes that are
      potentially able to contribute to drug resistance were investigated in paired
      samples of normal mucosa and tumors from 24 patients with colorectal cancer. In
      the tumors, glutathione S-transferase (GST) enzyme activity and content of GST-pi
      and P-170 glycoprotein were increased significantly compared with normal mucosa
      (P less than 0.03, P less than 0.003, and P less than 0.02, respectively). In
      contrast, GST-alpha and -mu, present in minor amounts compared with GST-pi, were
      downregulated in the tumor. Cytochrome P-450(4,5,6) and UDP-glucuronyltransferase
      (towards 4-nitrophenol and bilirubin) levels were significantly lower in the
      tumors (P less than 0.0001 and P less than 0.0002, respectively). Because
      decreased expression of cytochrome P-450 and increased levels of GST-pi and the P
      170 glycoprotein have been implicated in (multi)drug resistance, these findings
      strongly suggest that in colorectal tumors the inherent resistance is
      multifactorial. Research to overcome this resistance should therefore be directed
      toward a combined treatment that eliminates all of these different mechanisms.

PMID- 1353040
TI  - Molecular strategies in genetic diagnosis of transthyretin-related hereditary
      amyloidosis.
AB  - Transthyretin-related hereditary (TTR) amyloidoses represent a clinically
      heterogeneous group of diseases associated with various point mutations of the
      TTR gene. We propose a molecular strategy for the diagnosis of this group of
      disorders.

PMID- 1353042
TI  - Mucin and protein release in the rabbit jejunum: effects of bethanechol and vagal
      nerve stimulation.
AB  - The role of the vagus nerve and cholinergic mechanisms in the control of rabbit
      jejunal mucin and protein release was investigated in vivo. In anesthetized
      animals, a 10-cm segment of the jejunum was cannulated and perfused with saline.
      Perfusate was collected and analyzed for mucin (by immunoassay) and protein.
      Bilateral cervical vagotomy had no effect on basal mucin or protein output,
      suggesting that the vagus nerve does not exert a tonic control on jejunal
      macromolecule secretion. Electrical stimulation of the vagi did not alter mucin
      release, even in the presence of muscarinic cholinergic (scopolamine) or
      adrenergic (propranolol and phentolamine) blockade. In contrast, protein output
      increased significantly after vagal stimulation, an effect inhibited by
      scopolamine. In both vagotomized and vagally intact rabbits, the cholinergic
      agonist bethanechol (200 micrograms/kg intraperitoneally) induced a scopolamine
      sensitive increase in both mucin and protein output. Predominantly serum proteins
      were released into intestinal perfusates after vagal or cholinergic stimulation.
      It is concluded that the extrinsic vagus nerve does not regulate rabbit jejunal
      mucin secretion in vivo and that cholinergic control of intestinal goblet cells
      is implemented entirely by the intrinsic enteric nervous system. In addition,
      cholinergic or vagal stimulation increases intestinal vascular and epithelial
      permeability, resulting in the passage of serum proteins into the lumen, possibly
      by opening tight junctions and paracellular pathways.

PMID- 1353043
TI  - Maintenance of remission in Crohn's disease: is 5'-aminosalicylic acid the
      answer?

PMID- 1353044
TI  - The tricky business of testing drugs for gastroparesis.

PMID- 1353045
TI  - Apolipoprotein B-gene DNA polymorphisms (XbaI and EcoRI), serum lipids, and
      apolipoproteins in healthy Chinese.
AB  - The frequency of restriction fragment length polymorphisms (RFLPs) of the
      apolipoprotein B (apo B) gene, detected by XbaI and EcoRI, and their influence on
      serum lipids and apolipoproteins were studied in healthy Chinese of both sexes in
      Singapore. A total of 221 subjects (150 males, 71 females) were investigated for
      the XbaI and 159 subjects for the EcoRI polymorphisms, while serum lipids and
      apolipoprotein levels were available for 196 subjects. The frequency of the X2
      allele was found to be significantly lower in the Chinese than that reported in
      Caucasians from the United Kingdom (0.09 vs. 0.51, P less than 0.001). The
      haplotype frequencies were also significantly different between the Chinese and
      Caucasians with a higher frequency of X1R1 in the former compared to the latter
      (0.85 vs. 0.34, P less than 0.0001). The distribution of RFLP genotypes at both
      of the restriction sites was at Hardy-Weinberg equilibrium in all groups. The
      influence of the apo B RFLPs on serum lipids and apolipoprotein levels (apo AI,
      AII, and B) was studied by both residual and multiple regression analyses
      considering age, sex, body mass index (BMI), and genotypes as independent
      variables in all possible combinations. No association was observed between the
      apo B genotypes and serum lipids or apolipoprotein levels except for high density
      lipoprotein cholesterol (HDLC), apo AI and AII, with the X2 being associated with
      significantly lower levels of HDLC as well as apo AI and AII, the effect being
      stronger in males. These data raise the possibility that the mechanism of
      reported association between apo B polymorphism and coronary artery disease may
      be through effects on HDLC.

PMID- 1353046
TI  - DNA-binding activity of the murine homeodomain protein Hox-2.3 produced by a
      hybrid phage T7/vaccinia virus system.
AB  - Homeobox-containing genes encode transcription factors that, via the homeodomain,
      bind specifically to DNA. To study the DNA-binding properties of the murine
      homeodomain-containing protein, Hox-2.3, a hybrid expression system was used,
      combining gene expression by recombinant vaccinia virus (reVV) with bacteriophage
      T7 transcription. Expression was achieved by co-infecting HeLa cells with two
      reVVs, one expressing the T7-RNA polymerase-encoding gene directed by the VV
      promoter, P7.5, and another containing the Hox-2.3 coding sequence under control
      of a T7 promoter [Fuerst et al., Mol. Cell. Biol. 7 (1987) 2538-2544]. Co
      infected HeLa cells produced large amounts of full-length Hox-2.3 protein.
      Cytoplasmic and nuclear extracts from these cells were used to examine DNA
      binding specificity in vitro. reVV-produced Hox-2.3 protein bound to oligos that
      contained one or several copies of the common homeodomain-binding site, 5'-TCA
      ATTAAAT, and to a lesser extent to multiple (TAA) repeats. Using Southwestern
      blot analysis, no Hox-2.3-binding sites were detected in a region of the Hox-2
      cluster containing the Hox-2.3, Hox-2.4 and Hox-2.5 genes.

PMID- 1353047
TI  - A Xenopus borealis homeobox gene expressed preferentially in posterior ectoderm.
AB  - We have isolated a new homeobox-encoding gene (XhoxB.1) from Xenopus borealis
      which has a homeobox exon identical to that of the murine Hox1.7 gene, except for
      one amino acid. XhoxB.1 transcripts of 2.1 and 7.0 kb are first detected at the
      late gastrula stage, accumulate until the tailbud stage and are most abundant in
      the posterior third of the dorsal part of the embryo.

PMID- 1353048
TI  - Complications of peptic ulcer disease before and after the introduction of H2
      receptor antagonists.
AB  - This study was undertaken in order to evaluate the incidence of operations for
      bleeding, perforated and obstructing peptic ulcers in a defined population before
      and after the introduction of H2-receptor antagonists. The annual incidence of
      surgery for all peptic ulcer complications increased slightly, from 6.9 per 10(5)
      individuals in 1977 to 14.2 per 10(5) in 1989 (n.s.), whereas the annual
      incidence of operations for ulcer bleeding and perforation remained relatively
      stable, varying from 2.8 to 8.9 per 10(5) inhabitants and from 2.3 to 7.5 per
      10(5) inhabitants during the study period. Operations performed for gastric
      outlet obstruction did not increase, varying from 0.8 to 2.2 per 10(5)
      individuals over the study period. The annual proportion of emergency operations
      did not increase. Young men and old women were often operated on for bleeding (p
      less than 0.0001) and perforated ulcers (p less than 0.01). Duodenal ulcer
      bleeding and perforation were more frequent in the young patient groups. Overall
      mortality after operations performed for bleeding was 15%, and that after
      operations for perforation or obstruction, 17% and 8%, respectively. The mean age
      of the fatalities, 63 +/- 13 years, was significantly higher than that of those
      who survived after operation, 53 +/- 15 years (p 0.0001). Mortality was higher
      after operations for gastric ulcer complications (22%) than after operations for
      duodenal ulcer complications (10%) (p less than 0.01).

PMID- 1353049
TI  - Complications associated with total parenteral nutrition in infants with short
      bowel syndrome.
AB  - The use of total parenteral nutrition (TPN) in five out of six infants with short
      bowel syndrome (SBS) adaptation permitted enteral nutrition. The duration of TPN
      depended on the extent of the resection, whether it was proximal or distal, and
      the adaptation of the residual gut. Residual bowel measuring 10 cm required
      prolonged TPN in the sixth infant and was not compatible with survival. Catheter
      related complications were infection, malposition and dislodgement of the
      catheter. Metabolic complications were easily controlled by regulating the
      concentration of the infusate and the rate of the infusion. Osteopenia was common
      in prolonged TPN and was corrected with vitamin D supplementation. Cholestasis
      was the most common complication. It was demonstrated with elevation of gamma
      glutamyl-transpeptidase levels which became evident as early as six weeks after
      the introduction of TPN. Serum bilirubin and transaminase elevations were later
      manifestations. One infant died of hepatic decompensation. Late morphological
      manifestations were those of cholestatic changes with fibrosis. The biochemical
      abnormalities of cholestasis were reversible provided TPN was discontinued at an
      early stage.

PMID- 1353050
TI  - Effects of exogenous somatostatin and insulin on islet amyloid polypeptide
      (amylin) release from perfused rat pancreas.
AB  - This study examined the effects of exogenous somatostatin and insulin on the
      release of islet amyloid polypeptide (IAPP), or amylin, from the isolated
      perfused rat pancreas. Somatostatin inhibited the release of both amylin and
      insulin from the perfused pancreas to the same extent. The infusion of 10 nM
      somatostatin resulted in 40% inhibition of the secretion of both amylin and
      insulin induced by 11.1 mM glucose and 10 mM arginine, and this inhibition was
      significantly increased to 70% by the infusion of 100 nM somatostatin (p less
      than 0.05). The amylin/insulin molar ratios remained constant at 0.8% and were
      not changed by the infusion of somatostatin. On the other hand exogenous insulin
      at a concentration of 1.8 nM did not affect the release of amylin induced by 11.1
      mM glucose and 10 mM arginine, whereas 180 nM insulin slightly, although not
      significantly, inhibited the release of amylin by 15%. These findings suggest
      that the release of amylin may be negatively regulated by somatostatin and that
      circulating insulin may have no direct effect on the release of amylin at least
      at a physiological concentration.

PMID- 1353051
TI  - A new polymorphic site in the G6PD gene.
AB  - A polymorphic restriction site has been found in intron 11 of the gene for
      glucose-6-phosphate dehydrogenase (G6PD). This site is produced by a T----C
      substitution 13 bp upstream of exon 12, producing an NlaIII restriction site. In
      various populations there was a strong association between a T at nt 1311 of the
      G6PD cDNA and the presence of the NlaIII restriction site. Among African
      Americans, however, the presence of a C at nt 1311 was sometimes associated with
      the presence of a polymorphic NlaIII site.

PMID- 1353052
TI  - Exclusion of stromelysin-1, stromelysin-2, interstitial collagenase and
      fibronectin genes as the mutant loci in a family with recessive epidermolysis
      bullosa dystrophica and a form of cerebellar ataxia.
AB  - The interstitial collagenase gene (CLG), one of the main candidates in severe
      generalized recessive epidermolysis bullosa dystrophica (SGREBD), is closely
      linked to the stromelysin-1 (STMY1) and stromelysin-2 (STMY2) genes. These three
      loci map on chromosome 11 (q21-q22.3), where they constitute a cluster of genes
      coding for metalloproteinases involved in the degradation of the extracellular
      matrix (ECM). A recessive form of cerebellar ataxia of post-puberal onset (CLA1)
      has also been assigned to chromosome 11 (q14-q21). Since useful restriction
      fragment length polymorphisms (RFLPs) for the CLG gene are not available, we have
      studied the inheritance of the marker TaqI RFLP of the STMY1 gene in a North
      Italian family with a child affected by SGREBD, and his two sisters showing
      cerebellar ataxia (CA) of post-puberal onset. We have also studied the MspI RFLP
      of the fibronectin gene (FN1), which is located on chromosome 2q34-q36, and which
      codes for non-collagenous matrix proteins. Since we did not observe the
      segregation of the pathological phenotypes with STMY1 and FN1 RFLPs, we excluded
      the involvement of these genes in both the SGREBD and CA present in this family.
      The exclusion of the STMY1 gene indicates that the mutation causing SGREBD cannot
      be located in the CLG and/or STMY2 genes because of their proximity to the STMY1
      locus. These data also indicate that the CA form here reported is not
      attributable to alterations in regions close to the collagenase cluster on
      chromosome 11.

PMID- 1353053
TI  - Reduced recombination and paternal age effect in Klinefelter syndrome.
AB  - The parental origin of the additional sex chromosome was studied in 47 cases with
      an XXY sex chromosome constitution. In 23 cases (49%), the error occurred during
      the first paternal meiotic division. Maternal origin of the additional chromosome
      was found in the remaining 24 cases (51%). Centromeric homo- versus
      heterozygosity could be determined in 18 out of the 24 maternally derived cases.
      According to the centromeric status and recombination rate, the nondisjunction
      was attributable in 9 cases (50%) to an error at the first maternal meiotic
      division, in 7 cases (39%) to an error at the second maternal meiotic division
      and in 2 cases (11%) to a nullo-chiasmata nondisjunction at meiosis II or to
      postzygotic mitotic error. No recombination, and in particular none in the
      pericentromeric region, was found in any of the 9 cases due to nondisjunction at
      the first maternal meiotic division. Significantly increased paternal age was
      found in the paternally derived cases. Maternal age was significantly higher in
      the maternally derived cases due to a meiotic I error compared with those due to
      a meiotic II error. There were no significant clinical differences between
      patients with respect to the origin of the additional X chromosome.

PMID- 1353054
TI  - A 530kb YAC contig tightly linked to the Friedreich ataxia locus contains five
      CpG clusters and a new highly polymorphic microsatellite.
AB  - Friedreich ataxia (FA) is a severe autosomal recessive neurodegenerative disease.
      The defective gene has been previously assigned to chromosome 9q13-q21 by
      demonstration of tight linkage to the two independent loci D9S15 and D9S5.
      Linkage data indicate that FRDA is at less than 1 cM from both markers. Previous
      physical mapping has shown that probes defining D9S15 (MCT112) and D9S5 (26P) are
      less than 260 kb apart and are surrounded by at least six CpG clusters within 450
      kb, which might indicate the presence of "candidate" genes for FA. We isolated
      and characterized a 530 kb YAC (yeast artificial chromosome) contig that contains
      five of the CpG clusters. The YACs were used to search for new polymorphic
      markers needed to map FRDA precisely with respect to the cloned segment. In
      particular, we found a (CA)n microsatellite polymorphism, GS4, that detects 13
      alleles with a PIC value of 0.83 and allows the definition of haplotypes
      extending over 310 kb when used in combination with polymorphic markers at D9S5
      and D9S15.

PMID- 1353055
TI  - Three DNA markers for hypophosphataemic rickets.
AB  - This paper presents three markers, 16D/E, pHMAI (DXS208), and CRI-L1391 (DXS274),
      that show close linkage for X-linked hypophosphataemic rickets (HYP). DXS274 is
      closely linked to HYP (theta max = 0.00, Zmax = 4.20), and DXS41 (99.6), (theta
      max = 0.00, Zmax = 5.20). Marker 16D/E maps distal to the disease locus (theta
      max = 0.05, Zmax = 3.11). The pHMAI probe recognises the same restriction
      fragment length polymorphism (RFLP) as 99.6. Multipoint analysis suggests that
      the most probable order of loci is Xpter-(DXS43, 16D/E)-HYP-DXS274-(DXS208,
      DXS41)-Xcen. The location of DXS274 distal to HYP cannot be excluded, as no
      recombinants were observed between DXS274 and HYP, or between DXS274 and
      DXS41/DXS208. One of the families contains a large number of recombinants, four
      of which are double recombinants. This most probably means that the disease in
      this family maps elsewhere on the X chromosome or on an autosome, indicating
      locus heterogeneity.

PMID- 1353056
TI  - Alpha I/65 hereditary elliptocytosis in southern Italy: evidence for an African
      origin.
AB  - alpha I/65 Hereditary elliptocytosis (HE) is due to the duplication of TTG codon
      154 (leucine) of alpha-spectrin and is associated with a constant haplotype. It
      was encountered exclusively in African and American Blacks, and in North
      Africans. We assumed that it diffused from the Benin-Togo area to Northern
      Africa. We now report two South Italian families with alpha I/65 HE. The
      phenotype fully conformed to previous descriptions. The mode of transmission was
      dominant; however, the manifestations were more pronounced when the common, low
      expression level alpha V/41 allele occurred in trans to the alpha I/65 allele,
      also conforming to previous records. The mutation underlying alpha I/65 HE turned
      out to be, again, the duplication of TTG codon 154 and the associated haplotype
      was the same as that encountered previously (+-+; XbaI, PvuII, MspI). Thus, the
      alpha I/65 allele found in Italy must have been introduced from North Africa
      across the Sicilian channel and would ultimately have originated from the Benin
      Togo area. It would witness the same migratory stream as that followed by the
      Benin type haemoglobin S allele, which is also present in Southern Italy.

PMID- 1353057
TI  - Refined regional assignment of the human tissue factor pathway inhibitor (TFPI)
      gene to chromosome band 2q32 by non-isotopic in situ hybridization.

PMID- 1353058
TI  - PCR detection of a BclI RFLP in the G6PD gene of Caucasians.
AB  - We have calculated the frequencies of two alleles of the glucose-6-phosphate
      dehydrogenase gene in a randomly selected group of Caucasians. Allele 1 has a
      frequency of 82%, whereas that of allele 2 is 18%.

PMID- 1353059
TI  - Two PstI polymorphisms for the urokinase-type plasminogen activator receptor gene
      (PLAUR).
AB  - The cDNA probe puPAR-2 detects two PstI polymorphisms in the urokinase-type
      plasminogen activator receptor gene (PLAUR). This probe and the polymorphic
      system are described.

PMID- 1353060
TI  - Analysis of the basis of resistance and susceptibility of CD4+ T cells to human
      immunodeficiency virus (HIV)-gp120 induced anergy.
AB  - The resistance and susceptibility of T cells to human immunodeficiency virus
      (HIV)-gp120 induced anergy was examined. Antigen-dependent proliferation of
      polyclonal T cells was markedly inhibited by gp120, whereas from the analysis of
      monoclonal populations, T cells resistant to the effects of gp120 could be
      identified. Similarly, exposure of monoclonal T cells to gp120 in the absence of
      accessory cells, also demonstrated that some T cells could resist the induction
      of anergy. Loss of antigen recognition was associated with phenotypic modulation
      of CD3 and CD28, which was not observed in T cells resistant to functional
      inactivation by gp120. Modulation of CD4 was not related to induction of anergy
      in the monoclonal T cells examined in this study. Inhibition of T-cell responses
      by anti-CD4 antibodies was compared to that by gp120. Anti-CD4 antibodies, which
      cross-compete with gp120 for binding to CD4, inhibited the response to antigen of
      monoclonal T cells. In contrast, no tolerogenic signals were delivered by
      pretreating T cells with the anti-CD4 antibodies in the absence of accessory
      cells, indicating that inhibition was due to abrogation of the interaction of CD4
      with major histocompatibility complex (MHC) class II molecules expressed on
      accessory cells. Although the free CD4-binding region peptide of gp120 could
      inhibit polyclonal T-cell responses, only the carrier-bound peptide was able to
      modulate cloned T cells, suggesting a conformational requirement for functional
      inactivation through engagement of CD4. The results reported here using clonal
      CD4+ T-cell populations demonstrate that effects of gp120 on antigen-dependent
      proliferation are not uniform, and that therapeutic intervention might be
      directed at T-cell populations identified as susceptible to HIV-gp120 induced
      anergy.

PMID- 1353061
TI  - CD4+ T cells control measles virus infection of the central nervous system.
AB  - CD4+ T-cell lines with specificity for individual measles virus (MV) structural
      proteins were obtained from immunized Lewis rats. Isolated viral proteins, either
      purified from virions or bacterially expressed were used as antigens for
      immunological assays. All the cell lines secreted interferon-gamma (IFN-gamma)
      and interleukin-2 (IL-2), but were only weakly cytotoxic to autologous MV
      infected astrocytes. When cultured together with memory splenic B lymphocytes
      these T cells did not induce secretion of MV-specific antibodies. The in vivo
      function of the T-cell lines was investigated in our MV-encephalitis model in the
      Lewis rat. Within 24 hr of intracerebral infection, adoptive transfer of single
      MV protein-specific T cells either decreased or prevented the subsequent clinical
      and histological disease depending on the MV-protein specificity of the cell
      lines. Furthermore, there was an earlier and enhanced viral clearance from the
      CNS, without a change in the anti-MV antibody titres of serum and cerebrospinal
      fluid (CSF) of the recipients and the control-infected animals. Prior depletion
      of CD8+ T lymphocytes in the recipient animals did not abrogate the protection
      conferred by CD4+ T-cell lines, indicating that the acute viral CNS disease is
      being efficiently controlled by virus-specific CD4+ T cells.

PMID- 1353062
TI  - The organotin-induced thymus atrophy, characterized by depletion of CD4+ CD8+
      thymocytes, is preceded by a reduction of the immature CD4- CD8+ TcR alpha beta
      /low CD2high thymoblast subset.
AB  - Thymic changes in the rat induced by the thymus atrophy-inducing organotin
      compound di-n-butyltin dichloride (DBTC) were examined using FACS analyses. The
      number of CD4+CD8+ thymocytes was reduced by DBTC treatment from Day 2 onwards
      and reached minimum level on Days 4 and 5 after dosing. On these days the CD4-CD8
      and both the CD4-CD8+ and CD4+CD8- subsets were not affected. On Day 2 we
      observed a reduced proportion of transferrin receptor (CD71)-positive CD4-OX44-
      cells, representing the cycling immature CD4-CD8+ cells, and of CD71+OX44- cells,
      representing the cycling CD4+CD8+ cells, but not of CD71+CD4-CD8- cells. When
      compared to controls, the FSChigh cell population of DBTC-treated rats contained
      less CD4-OX44- and OX44- cells, which were further characterized as CD2high and T
      cell receptor (TcR)alpha beta- low. Moreover, fewer TcR alpha beta high cells
      were detected in the OX44- thymoblast subset of DBTC-treated rats. The number of
      CD4-CD8- thymoblasts appeared marginally decreased while the numbers of CD4+OX44+
      cells, representing mature CD4+ cells, were not affected. These data indicate
      that DBTC causes a preferential initial depletion of immature CD4-CD8+CD2high TcR
      alpha beta-low thymoblasts. This initial event may result in a decreased
      formation of CD4+CD8+ thymoblasts and of small CD4+CD8+ thymocytes. These
      characteristics of the initially depleted subset indicate a specific anti
      proliferative effect of DBTC and may give clues for the mechanism involved in the
      induction of thymus atrophy.

PMID- 1353063
TI  - Role of adhesion molecules in lymphokine-activated killer cell killing of bladder
      cancer cells: further evidence for a third ligand for leucocyte function
      associated antigen-1.
AB  - The lysis of eight human bladder cancer cell lines by lymphokine-activated killer
      cells (LAK) was found to be partially dependent upon the expression by the target
      cell of either intercellular adhesion molecule-1 (ICAM-1) or intercellular
      adhesion molecule-2 (ICAM-2). Using adhesion blockade studies these molecules
      were found to contribute towards sensitivity to lysis. Tumour lines of low grade
      (G1) did not constitutively express ICAM-1, but were found to express ICAM-2.
      High grade cells (G2, G3), however, only constitutively expressed ICAM-1 on their
      cell surface. Interferon-gamma (IFN-gamma) induced and augmented the expression
      of ICAM-1 by all except one of the cell lines (UMUC3) in a dose- and time
      dependent manner. This was accompanied by an increased susceptibility to
      lymphokine-activated killer mediated cytolysis. Anti-ICAM-1 antibodies partially
      inhibited the increase in cell lysis due to IFN-gamma. However, this inhibition
      was not complete. When effector cells were treated with antibodies to leucocyte
      function-associated antigen-1 (LFA-1) the inhibition of lysis was greater and
      ranged from 72 to 96% with a mean of 87% inhibition. These results suggest that
      the increased sensitivity of IFN-gamma-treated bladder cancer cell lines to LAK
      cells is partially attributable to the induction of ICAM-1. However, blocking of
      ICAM-1 with antibodies could only partially inhibit the increased LFA-1-dependent
      lysis. This supports recent evidence for the existence of an additional ligand
      for LFA-1, other than ICAM-1 and ICAM-2.

PMID- 1353065
TI  - International workshop on technology assessment of PACS. The Netherlands, May 26
      27, 1991.

PMID- 1353064
TI  - Expression of interleukin-6 receptor on blood lymphocytes without in vitro
      activation.
AB  - A monoclonal antibody against the interleukin-6 receptor (IL-6R) has been used in
      a high-sensitivity immunofluorescence technique to study receptor expression on
      unstimulated blood lymphocytes. Most CD4 cells express IL-6 receptor, whilst a
      small and variable proportion of CD8 and B cells are positive. CD4+ cells express
      higher levels of receptor than CD8+ T cells, and CD45RO+ cells express higher
      levels than CD45RA cells.

PMID- 1353066
TI  - Molecular probe analysis of Shigella dysenteriae type 1 isolates from 1940 to
      1987.
AB  - Fourteen strains of Shigella dysenteriae type 1 (Shiga bacillus) isolated from
      people in diverse locations from 1940 to 1987 were studied. Southern
      hybridization with three cloned Escherichia coli genes, Shiga-like toxin I
      (SLTI), frd, and ompF, was used to determine restriction fragment length
      polymorphism (RFLP) of the genomic DNA of these strains. Digestion with each of
      four restriction endonucleases generated fragments of identical size to which the
      frd and ompF hybridized for each of the 14 strains, indicating the conservation
      of these genes and their flanking sequences. In contrast, after digestion with
      HindIII, EcoRV, and ClaI and probing with SLTI, there were RFLP among the
      strains. The results showed three clones of the Shiga bacillus, and suggested
      that dissemination of a single clone may continue for decades within a wide
      geographical area.

PMID- 1353067
TI  - Insect peptide hormones, an overview of the present literature.
AB  - A comprehensive overview of the recent state of the art of insect peptide
      hormones with chemical structures is presented. An increased interest in insect
      neuropeptides and dynamic development of that research area has been influenced
      by a rapid improvement of instrumentation necessary for isolation and structural
      characterization. Several research teams have studied the relationships between
      biological properties of insect and vertebrate peptide hormones. Thus hormones
      from the AKH family can be considered glucagon counterparts, whereas the
      myotropic hormones such as proctolin and Lem-PK (LPK) are a substance P
      equivalent. Insect melanization hormones Bom-MRCH in their structural
      characteristics and properties resemble those of mammal MSH, and leucosulfakinins
      Lem-SK-I and -II show some similarities with gastrin II and cholecystokinin.
      Bombyxin-II (Bom-PTTH-II) reveals a structural homology with human insulin and
      similar biological properties to adenocorticotropic mammal hormone. Allatostatin
      (Dip-JHS-I) may be compared to somatostatin as it can be inferred from the
      observations that this peptide modulates JH secretion in cockroach, Blattella
      germanica. Determination of the primary structure of eclosion hormones Mas-EH and
      Bom-EH-II as well as the amino acid sequence of allatotropin and allatostatin is
      a significant contribution to the understanding of the molecular mechanisms of
      metamorphosis and insect development.

PMID- 1353068
TI  - Preparation of protected peptide amides using the Fmoc chemical protocol.
      Comparison of resins for solid phase synthesis.
AB  - Different resins were examined for their potential use in the solid phase
      synthesis of protected peptide amides using the 9-fluorenylmethoxycarbonyl (Fmoc)
      chemical protocol. The model protected peptide amide BocTyr-Gly-Gly-Phe-Leu
      Arg(Pmc)NH2 (1) was synthesized on both the acid-labile 4-(2',4'-dimethoxyphenyl
      Fmoc-aminomethyl)phenoxy resin (Rink amide resin) (2) and on resins containing
      the base-labile linker 4-hydroxymethylbenzoic acid. Of the resins examined only
      the methylbenzhydrylamine resin containing the 4-hydroxymethylbenzoic acid
      linkage, which was cleaved by ammonolysis in isopropanol, gave the model peptide
      1 in good overall yield (53% including functionalization). Thus the synthesis of
      protected peptide amides by solid phase synthesis using Fmoc-protected amino
      acids with t-butyl-type side chain protecting groups is feasible. The choice of
      peptide-resin linkage and its cleavage conditions, however, are critical to the
      success of such syntheses. The potential application of this synthetic strategy
      to the preparation of novel peptide amides is discussed.

PMID- 1353069
TI  - Hb City of Hope [beta 69(E13)Gly----Ser] in Italy: association of the gene with
      haplotype IX.
AB  - Hb City of Hope [beta 69(E13)Gly----Ser] was detected by reversed phase high
      performance liquid chromatography in an asymptomatic carrier from Naples,
      Southern Italy. The amino acid substitution, identified by fast atom bombardment
      mass spectrometry, was due to a TGG----TGA substitution as assessed by DNA
      sequencing. Analysis of the chromosomal background indicates that the globin gene
      cluster containing the mutant gene has most probably been rearranged by a
      recombination event, since the mutation was associated with restriction fragment
      length polymorphism haplotype IX, instead of haplotype I, as previously reported.

PMID- 1353070
TI  - An immunohistochemical study of the catecholamine synthesizing enzymes and
      neuropeptides in the female guinea-pig uterus and vagina.
AB  - The uterus and vagina of the guinea pig have been examined, region by region, for
      acetylcholinesterase, tyrosine hydroxylase, dopamine beta-hydroxylase and
      aromatic amino acid decarboxylase activity, as well as for the neuropeptides,
      neuropeptide Y, vasoactive intestinal peptide, substance P, enkephalin and
      somatostatin. No acetylcholinesterase activity was localized in the uterus,
      though it was present in associated paracervical ganglion tissues. Of the
      catecholamine-synthesizing enzymes, tyrosine hydroxylase and dopamine beta
      hydroxylase activity was found virtually throughout the reproductive tract,
      whereas aromatic amino acid decarboxylase activity was restricted in its
      distribution. Neuropeptide distribution was quite varied. Neuropeptide Y was
      found throughout the endometrium/submucosa but only in the muscularis of the
      vagina and not in the myometrium. Substance P was localized in the vagina and
      uterine horn, though not the body of the uterus. Vasoactive intestinal peptide
      was present in all regions of the endometrium/submucosa, but not in the
      myometrium of the uterine horn. Enkephalin and somatostatin were not localized in
      any part of the reproductive tract examined, apart from paracervical ganglion
      tissues. The types and significance of the nerves supplying the reproductive
      tract are discussed.

PMID- 1353071
TI  - Hypothalamic neurotransmitter concentrations and meat quality in stressed pigs
      offered excess dietary tryptophan and tyrosine.
AB  - Pale, soft, exudative (PSE) pork occurs, for the most part, from environmental
      stress on the pig. Amino acid intake may be related to stress susceptibility
      through hormone and neurotransmitter induction. Two experiments were conducted to
      determine whether supplementation of 5 g of tryptophan (TRP) or 10 g of tyrosine
      (TYR) per kilogram of a 14% CP diet would alter the response of pigs to stress as
      measured by hypothalamic neurotransmitter concentrations and incidence of PSE.
      Twenty-four (Exp. 1) and 36 (Exp. 2) 92-kg pigs were offered one of three diets:
      control, TRP-, or TYR-supplemented for 5 d before slaughter. Dietary TRP or TYR
      supplementation in Exp. 1. doubled (P less than .05) plasma TRP and TYR
      concentrations, respectively, and increased (P less than .05) 5
      hydroxytryptamine, dihydroxyphenyl ethylamine, dihydroxyphenyl acetic acid, and
      homovanillic acid concentrations in the hypothalamus. Pigs that exhibited stress
      at slaughter had lower (P less than .05) hypothalamic concentrations of
      epinephrine, norepinephrine, and 5-hydroxytryptamine. In Exp. 2, pigs were
      trucked 55 km to a commercial meat packing facility and slaughtered without a
      rest period. This handling procedure was designed to invoke a high incidence of
      PSE pork and thus be a strong test of treatments. Supplemental dietary amino
      acids seemed to alter the frequency distribution of the severity of PSE pork.
      These data indicate that dietary manipulation of amino acid precursors of
      neurotransmitters may offer a practical means of reducing stress response in
      swine.

PMID- 1353072
TI  - Human mammary epithelial cells in primary culture reflect c-myc and c-erbB-2 gene
      copy number in tissue.

PMID- 1353073
TI  - Serial cultivation of normal human keratinocytes: a defined system for studying
      the regulation of growth and differentiation.
AB  - We have developed a defined method for human epidermal keratinocyte culture. The
      minimally supplemented basal medium supported establishment of primary cultures
      from neonatal foreskin in a defined environment. It also supported serial
      cultivation and rapid expansion of cell number. Casein replaced serum for defined
      cryopreservation. Cells were serially cultivated in medium containing 0.08 mM
      calcium. The rate of cell division however remained high after addition of 1.8 mM
      calcium. The particulate transglutaminase activity of the cultures was low at
      confluence, even in the presence of 1.88 mM calcium, indicating an enrichment of
      the basal cell population. Culture with small amounts (0.3%) of chelated serum
      increased particulate transglutaminase activity approximately 2.2-fold in low
      calcium cultures and approximately 3.5-fold in high calcium cultures. A gradual
      reduction in growth rate of serum-treated cultures upon serial cultivation also
      indicated a depletion of cells with basal cell character. Bovine hypothalamic
      extract and cholera toxin were able to avert, in part, the differentiation
      promoting effects of serum. Keratinocytes serially cultivated in the defined
      medium maintained the ability to develop normally into a morphologically
      differentiated epidermis.

PMID- 1353074
TI  - Gamma glutamyl transpeptidase in meningitis.
AB  - Gamma glutamyl transpeptidase (GGTP) was measured serially in cerebrospinal fluid
      (CSF) and serum in 23 cases of meningitis (15 pyogenic and 8 tuberculous
      meningitis) and an equal number of age and sex matched healthy controls, to find
      out its diagnostic and prognostic significance in meningitis. GGTP activity was
      significantly elevated (p less than 0.001) in CSF and serum in meningitis as
      compared to control subjects. Levels were significantly higher in pyogenic as
      compared to tuberculous meningitis (p less than 0.001) and in CSF than in serum
      (p less than 0.001). The maximum elevation was seen on the 1st day and thereafter
      the activity declined in the majority (65.2%) of cases. However, in 3 cases of
      pyogenic meningitis and 5 cases of tuberculous meningitis, the GGTP activity on
      subsequent estimation increased serially; all these 8 cases died. It is concluded
      that CSF GGTP activity is significantly elevated in meningitis and serial rise in
      its activity is associated with poor prognosis and even fatal outcome.

PMID- 1353075
TI  - Misuse of antacid and H2 receptor antagonists in routine clinical practice.

PMID- 1353076
TI  - Dephosphorylation of the guanylyl cyclase-A receptor causes desensitization.
AB  - Atrial natriuretic peptide (ANP) binds to the guanylyl cyclase-A (GC-A) receptor
      found in tissues such as the kidney and adrenal gland, resulting in marked
      elevations of the intracellular signaling molecule, cGMP. Here, GC-A is shown to
      exist as a phosphoprotein when expressed in human embryonic 293 cells. The 32P is
      principally associated with phosphoserine, with only trace amounts of
      phosphothreonine. The addition of ANP causes a time-dependent dephosphorylation
      of the receptor, as well as desensitization, which is not due to an ANP-mediated
      decrease in the amount of receptor protein. The mobility of GC-A on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis increases after treatment of
      cells with ANP, and protein phosphatase 2A induces the same mobility shift. The
      protein phosphatase also catalyzes dephosphorylation of GC-A, and this is
      directly correlated with decreases in ANP-stimulatable guanylyl cyclase activity.
      Okadaic acid, an inhibitor of protein phosphatase 2A, blocks both the
      dephosphorylation and the desensitization. Therefore, in contrast to many other
      cell surface receptors, GC-A is desensitized by ligand-induced dephosphorylation.

PMID- 1353077
TI  - Immunoprecipitation of alpha 2a-adrenergic receptor-GTP-binding protein complexes
      using GTP-binding protein selective antisera. Changes in receptor/GTP-binding
      protein interaction following agonist binding.
AB  - The nature of the interaction of cloned alpha 2a-adrenergic receptors from LLC
      PK1-O clone cells with G proteins was investigated using an immunoprecipitation
      approach. Following solubilization of the alpha 2a receptors, antiserum 8730,
      which is directed against the C-terminal region of Gi alpha, immunoprecipitated
      alpha 2a receptor-Gi alpha complexes. The immunoprecipitation was specific since
      it could be blocked by the peptide to which antiserum 8730 was generated.
      Antisera 3646 (anti-Gi alpha 1), 1521 (anti-Gi alpha 2), and 1518 (anti-Gi alpha
      3) immunoprecipitated solubilized alpha 2a receptor-Gi alpha complexes,
      indicating that all three Gi alpha subtypes couple with the alpha 2a receptor.
      Antiserum 9072, which is directed against the C-terminal region of G(o)alpha,
      immunoprecipitated solubilized alpha 2a receptor-G alpha complexes indicating
      that these receptors are also coupled to G(o)alpha. Antiserum 8132, which is
      directed against G beta 36, immunoprecipitated solubilized alpha 2a receptors
      while the G beta 35 antiserum 8129, did not, indicating that alpha 2a receptors
      selectively associate with G beta 36. The binding of the partial agonist p
      aminoclonidine to the solubilized alpha 2a receptor alters the association of the
      receptor with G proteins. Following p-aminoclonidine binding to the solubilized
      alpha 2a receptor, the ability of the C-terminal directed G alpha antisera 8730
      and 9072 to coimmunoprecipitate the alpha 2a receptor-G alpha complex was greatly
      reduced. The effect of p-aminoclonidine was concentration dependent, mimicked by
      the full agonist UK 14304 and blocked by the alpha 2 receptor antagonist
      yohimbine. In contrast, antisera directed against internal regions of Gi alpha
      and G(o)alpha, immunoprecipitated the agonist-bound and agonist-free alpha 2a
      receptor equally well. These findings indicate that following the binding of
      agonists to the alpha 2a receptor, Gi alpha and G(o)alpha remain physically
      associated with the receptor but either the conformation of G alpha linked to the
      receptor or the conformation of the receptor itself is modified such that the
      epitope for the C-terminal directed anti-Gi alpha and anti-G(o)alpha antisera are
      not accessible. These agonist-induced conformational changes in the alpha 2a
      receptor-G alpha complex may be important for the activation of the G protein and
      the stimulation of the alpha 2a receptor signal transduction pathway.

PMID- 1353078
TI  - Free amino acid dynamics in marine methanogens. beta-Amino acids as compatible
      solutes.
AB  - Methanogenic archaebacteria respond to osmotic stress by accumulating a series of
      organic molecules which function as compatible solutes. In two strains of marine
      methanogenic archaebacteria, Methanogenium cariaci and Methanococcus
      thermolithotrophicus, four key organic solutes are observed: L-alpha-glutamate,
      beta-glutamate, N epsilon-acetyl-beta-lysine, and betaine. The first three of
      these are synthesized de novo; betaine is transported into the Mg. cariaci cells
      from the medium. Mesophilic Mg. cariaci will preferentially transport betaine
      from the extracellular medium if it is present to counterbalance the external
      NaCl. In its absence it synthesizes N epsilon-acetyl-beta-lysine as the dominant
      osmolyte. This zwitterionic compound occurs at levels in Mg. cariaci which are
      considerably greater (based on mumol/mg of protein) than in Mc.
      thermolithotrophicus grown in media of the same ionic strength. Intracellular
      potassium ion concentrations, determined by 39K NMR spectroscopy and atomic
      absorption, differ significantly in the two cells. In Mc. thermolithotrophicus,
      intracellular K+ is balanced by the total concentration of anionic amino acid
      species, glutamate, and beta-glutamate. Turnover of the organic solutes has been
      monitored using 13C-pulse/12C-chase, and 15N-pulse/14N-chase experiments. Both
      beta-amino acids exhibit slower turnover rates when compared to L-alpha-glutamate
      or aspartate, consistent with their roles as compatible solutes. Biosynthetic
      information for the beta-amino acids is also provided by 13C-labeling
      experiments. beta-Glutamate shows a lag in 13C uptake from 13CO2, indicative of
      its biosynthesis from a precursor (probably a macromolecule) not in equilibrium
      with the soluble L-alpha-glutamate pool. Confirmation of a novel route for beta
      glutamate synthesis and the production of the beta-lysine moiety from the
      diaminopimelate pathway is deduced from [13C2]acetate labeling patterns.

PMID- 1353079
TI  - Monoclonal antibodies against the extracellular domain of the erbB-2 receptor
      function as partial ligand agonists.
AB  - In this paper we describe the isolation and characterization of four monoclonal
      antibodies (FRP5, FSP16, FWP51, and FSP77) which specifically recognize the human
      erbB-2 protein. All of the antibodies recognize epitopes on the extracellular
      domain of the receptor protein. FRP5 and FSP16 compete with one another for
      binding while FWP51 and FSP77 each recognize a different epitope. The effects of
      the antibodies on the erbB-2 receptor protein have been analyzed. Two different
      erbB-2-expressing cell lines, SKBR3 breast tumor cells and HC11 R111 cells, were
      examined. The SKBR3 cells express approximately 1 x 10(6) molecules of the erbB-2
      protein/cell; HC11 R111 cells, a clone of mouse mammary epithelial cells derived
      by transfection of a human erbB-2 expression plasmid, contain 10-fold less erbB-2
      protein than the SKBR3 cells. Treatment of the two cell lines with FRP5, FSP16,
      and FWP51 led to a rapid increase in the phosphotyrosine content of the erbB-2
      protein. Three of the antibodies, FRP5, FSP16, and FSP77, stimulated the turnover
      of the erbB-2 protein. Binding of the antibodies did not stimulate DNA synthesis
      in HC11 R111 cells. Thus, the erbB-2-specific monoclonal antibodies behave as
      partial ligand agonists. The antibodies were examined for their effects upon the
      growth of SKBR3 and HC11 R111 cells. The growth of SKBR3 cells was inhibited by
      90% following long term treatment of the cells with FSP77.

PMID- 1353080
TI  - Only three mutations account for almost all defective alleles causing adenine
      phosphoribosyltransferase deficiency in Japanese patients.
AB  - We analyzed mutant alleles of adenine phosphoribosyltransferase (APRT) deficiency
      in Japanese patients. Among 141 defective APRT alleles from 72 different
      families, 96 (68%), 30 (21%), and 10 (7%) had an ATG to ACG missense mutation at
      codon 136 (APRT*J allele), TGG to TGA nonsense mutation at codon 98, and
      duplication of a 4-bp sequence in exon 3, respectively. The disease-causing
      mutations of only four (3%) of all the alleles among Japanese remain to be
      elucidated. Thus, a diagnosis can be made for most of the Japanese APRT-deficient
      patients by identifying only three disease-causing mutations. All of the
      different alleles with the same mutation had the same haplotype, except for
      APRT*J alleles, thereby suggesting that alleles with the same mutation in
      different families were derived from the same ancestral gene. Evidence for a
      crossover or gene conversion event within the APRT gene was observed in an APRT*J
      mutant allele. Distribution of mutant alleles encoding APRT deficiency among the
      Japanese was similar to that seen in cystic fibrosis genes among Caucasians and
      Tay-Sachs genes among the Ashkenazi Jews.

PMID- 1353083
TI  - Terazosin: a new alpha adrenoceptor blocking drug.
AB  - Terazosin (Hytrin; Abbott Laboratories, North Chicago, IL) is a new, selective
      alpha 1-adrenoceptor blocking agent used on once-a-day basis for therapy of mild
      to-moderate hypertension. Its pharmacologic properties are similar to those of
      prazosin. Terazosin however, differs from prazosin in that its water solubility
      is 25 times greater than that of prazosin and its elimination half-life is about
      three times that of prazosin. Greater water solubility facilitates intravenous
      formulation, and longer half-life allows once-daily administration of terazosin.
      Terazosin is effective in lowering blood pressure and has a beneficial effect on
      plasma lipid profile. The major advantage of terazosin compared with prazosin,
      however, is its long duration of action. Terazosin is safe and effective when
      used in combination with diuretics and other antihypertensive agents, and in the
      long-term treatment of patients with mild to moderate essential hypertension.

PMID- 1353081
TI  - Recombinant interleukin-12 suppresses the synthesis of immunoglobulin E by
      interleukin-4 stimulated human lymphocytes.
AB  - Interleukin-12 is a recently discovered lymphokine displaying an array of in
      vitro activities suggesting a major role in protective immunity against
      infectious agents like viruses. This study provides evidence that IL-12 may also
      be implicated in the selection of the immunoglobulin isotypes. We show that
      picomolar concentrations of rIL-12 markedly inhibit the synthesis of IgE by IL-4
      stimulated PBMC. The suppression of IgE is observed at the protein and at the
      mRNA levels, it is isotype specific, and it is abolished by neutralizing anti-IL
      12 mAbs. IL-12 may suppress IgE synthesis by: (a) inducing the production of IFN
      gamma, a known inhibitor of IgE synthesis and (b) by a novel mechanism which is
      IFN-gamma independent. The best evidence for this is from studies on IgE
      synthesis by IL-4-plus hydrocortisone-stimulated umbilical cord blood
      lymphocytes, which do not produce detectable amounts of IFN-gamma. In such
      cultures, rIL-12 inhibits IgE synthesis even in the presence of a large excess of
      neutralizing anti-IFN-gamma mAb.

PMID- 1353082
TI  - Papillon-Lefevre syndrome. Characterization of peripheral blood and gingival
      lymphocytes with monoclonal antibodies.
AB  - A 14-year-old boy with typical features of Papillon-Lefevre syndrome (PLS) is
      presented. The purpose of this report was to study the immunopheno-typic features
      of the peripheral blood and gingival tissue lymphocytes with monoclonal
      antibodies in the patient. Peripheral blood T-cells, helper-T cells, suppressor-T
      cells, HLA-DR+ cells and IL-2R+ cells were determined using appropriate
      monoclonal antibodies and indirect immunofluorescence methods. B-cells were
      identified using the direct immunofluorescence technique. The gingival tissue was
      processed for both histopathological and immunohistological examinations.
      Gingival tissue lymphocytes were identified using monoclonal and polyclonal
      antibodies with the immunoperoxidase technique. Although we have not detected any
      significant alterations in the peripheral blood B-cell and T-cell populations, NK
      cells were significantly increased. HLA-DR+ cells and IL-2R+ cells were within
      normal limits. Histopathology of the diseased tissue revealed predominance of
      plasma cells in the lamina propria. The majority of the plasma cells were bearing
      IgG isotype. Most of the CD3+ T-cells were located beneath the pocket epithelium
      with an almost equal distribution of CD4+ and CD8+ T-lymphocytes, in situ. These
      findings indicate that PLS is a IgG+ plasma cell dominated lesion with the
      participation of T-lymphocytes, having similar distributions of both subsets.
      While the etiopathogenesis of the syndrome still has to be elucidated, these
      immunohistological findings could be used for further studies in this intriguing
      entity.

PMID- 1353084
TI  - Physical restraint use and cognitive decline among nursing home residents.
AB  - OBJECTIVE: This study investigated the association between physical restraint use
      and decline in cognition. DESIGN: Cohort analytic study describing changes in
      resident characteristics. SETTING: Eight nursing homes, both urban and suburban,
      operated by a proprietary corporation in a large metropolitan area. PARTICIPANTS:
      437 nursing home admissions, with 201 remaining at 1 year. MAIN OUTCOME MEASURES:
      Cognitive status was measured by geropsychiatrists, using the Folstein Mini
      Mental State Exam, during a psychiatric evaluation of the resident. Daily
      restraint use was documented from nursing orders. Observations were made at 2
      weeks, 10 weeks, and 1 year. RESULTS: Restraint use alone and in combination with
      neuroleptic use was associated with poor cognition. Other variables associated
      with poor cognitive scores were: ADL impairment, poor adaptive behavior, and
      longer time in the nursing home. The use of neuroleptics alone was not
      significant. Variables which were associated with good cognitive status were:
      being non-ambulatory but without dementia and having strong social support.
      CONCLUSIONS: These findings raise the possibility that restraint use may
      contribute to cognitive impairment, specifically among residents who have
      moderate to no cognitive impairment at admission; however, the findings do not
      exclude an alternative explanation that residents undergoing cognitive decline
      are more likely to be put in restraints. Further research is needed to understand
      whether factors which can be manipulated contribute to cognitive decline.

PMID- 1353085
TI  - Microbial contamination of brushes used for preoperative shaving.
AB  - Microbial contamination of brushes used for preoperative shaving was
      investigated. Of the 24 brushed examined, 18 were contaminated with 10(6)-10(9)
      colony forming units (cfu) per brush. Non-fermentative Gram-negative bacilli such
      as Pseudomonas aeruginosa and Xanthomonas maltophilia, and yeast-like fungi such
      as Candida parapsilosis were the primary contaminants. The mean bacterial count
      on the skin after the use of contaminated brushes (having a mean bacterial count
      2.2 x 10(8) cfu) in 14 subjects was 4.6 x 10(5) cfu 25 cm-2, which was about 100
      times (p less than 0.001) the control level. Contaminated brushes could not be
      disinfected with 80% ethyl alcohol, 0.1% sodium hypochlorite or 0.5%
      chlorhexidine. These findings suggest that the use of brushes should be avoided
      for preoperative shaving with a razor, and that sterile gauze and shaving foam
      should be used instead of a brush and soap.

PMID- 1353086
TI  - Bacterial contamination of enteral feeds as a possible risk of nosocomial
      infection.
AB  - The degree of microbiological contamination in enteral diets was studied and the
      possible infectious complications that could arise in the patient after
      administration of an enteral feed were evaluated. Of the 208 diets studied, 56
      (26.9%) were contaminated and 152 (73.1%) were sterile. Of the 56 contaminated
      diets, 11 could be used as delivered, but the other 45 required further
      modification. Of the patients who had received enteral feeding, 43 developed
      gastrointestinal symptoms in the first 24 h (fever, vomiting, abdominal pain and
      diarrhoea). Twenty-nine (67.4%) had received a contaminated diet and 14 (32.6%)
      an uncontaminated one. We conclude that contamination of enteral feeds may
      constitute a risk factor for nosocomial infection, and consider it necessary to
      carry out epidemiological surveillance in order to control the factors which may
      lead to contamination of enteral diets.

PMID- 1353087
TI  - Partial characterization of an endemic strain of a methicillin- and
      aminoglycoside-resistant Staphylococcus aureus (MARSA) homogeneously resistant to
      beta-lactam antibiotics.
AB  - Selected strains of methicillin- and aminoglycoside-resistant Staphylococcus
      aureus (MARSA) were subjected to a preliminary examination. They were
      representative of a larger group collected in a routine clinical microbiology
      laboratory over a period of 2 years. MARSA was endemic in the associated
      hospital. The characteristics investigated were antimicrobial resistance, the
      production of beta-lactamase, free and bound coagulase, protein A, DNA-ase,
      urease, lipase and pigment. The MARSA strains were generally indistinguishable,
      other than in their antimicrobial resistances. The resistance to methicillin was
      completely homogeneous. Except with imipenem, growth extended to the edge of
      discs containing methicillin and the other beta-lactam antibiotics tested when
      the strains were cultured at 37 degrees C on media without added salt.
      Homogeneous resistance may confer an epidemiological advantage on strains of this
      phenotype.

PMID- 1353088
TI  - Staphylococcus aureus still colonizes the untreated neonatal umbilicus.
AB  - Two different neonatal umbilical cord treatment regimens were studied
      prospectively. Although a greater proportion of cords had separated by the
      seventh day in those babies not treated with topical antiseptics (47% vs. 26%),
      there was a significant excess (53% vs. 30%) of umbilical colonization by
      Staphylococcus aureus compared to those neonates whose cords were treated with
      alcohol wipes and hexachlorophane powder. The main purpose of treating cords is
      to prevent significant S. aureus colonization, and therefore current proposals to
      stop antiseptic treatment of umbilical cords should be disregarded.

PMID- 1353089
TI  - Handwashing in a neonatal intensive care nursery: product acceptability and
      effectiveness of chlorhexidine gluconate 4% and triclosan 1%.
AB  - The effectiveness of triclosan 1% w/v against methicillin-resistant
      Staphylococcus aureus (MRSA) and its effect on skin were compared with
      chlorhexidine gluconate 4% w/v ('Hibiclens') in a 7-week trial. Clinical
      information of MRSA rates obtained during the previous 10 months and results from
      earlier user acceptability trials were included. The average number of new cases
      of MRSA per week was reduced from 3.4 to 0.14 (P less than 0.0001) in the
      experimental ward whilst no significant changes occurred in the control ward.
      Staff reported less skin damage and a higher rate of acceptance with the
      experimental product. Based on results of the trial, a proposal to introduce
      triclosan for a 12-month study period has been accepted.

PMID- 1353090
TI  - Evaluation of a commercial chemiluminescent gene probe system 'AccuProbe' for the
      rapid differentiation of mycobacteria, including 'MAIC X', isolated from blood
      and other sites, from patients with AIDS.
AB  - Optimal therapy of mycobacterial infections in acquired immunodeficiency syndrome
      (AIDS) is difficult to achieve because of the time needed for a conventional
      culture to differentiate between Mycobacterium avium-intracellulare complex
      (MAIC) and Mycobacterium tuberculosis complex (MTBC). The recent commercial
      availability of gene probing techniques has introduced the potential for more
      rapid differentiation. We have evaluated the suitability of this technique. The
      specificity of the chemiluminescent gene probe system 'AccuProbe' was determined
      for differentiating mycobacterial isolates from 114 AIDS patients. 'AccuProbe'
      was 100% specific for MTBC isolates (21 of 21 isolates). Using two separate
      probes to MAIC and 'M. avium-intracellulare complex subtype X' (MAIC-X),
      'AccuProbe' was 96% specific (87 of 91 isolates) with 5% of isolates belonging to
      the MAIC-X group. There were no cross-reactions between any of the probes. Using
      a modification of the manufacturer's protocol, 'AccuProbe' was used in a 6-month
      trial for the rapid differentiation of mycobacteria grown from 'Bactec' blood
      culture. Fifty-seven isolates (31 patients) from 805 Bactec 13A blood cultures
      (510 patients) were investigated. Ninety-nine per cent of isolates were able to
      be identified after a mean incubation period of 2.1 weeks (SD 1.2 weeks). Ninety
      three per cent of isolates were reported with a presumptive identification the
      same day and 99% by the day after the culture flagged positive.

PMID- 1353091
TI  - Failure of ciprofloxacin to eradicate carriage of Salmonella.

PMID- 1353092
TI  - Non-tuberculous mycobacteria in a hospital's piped water supply.

PMID- 1353093
TI  - 'Silverline', a device for the prevention of nosocomial bacteriuria?

PMID- 1353094
TI  - Efficacy of topical antiseptics on staphylococcal colonization of neonates.

PMID- 1353095
TI  - Nosocomial bacteraemia in hospital staff caused by Haemophilus influenzae type b.

PMID- 1353096
TI  - Recovery of coliforms from the hands of nurses and patients: activities leading
      to contamination.
AB  - Coliform type organisms were recovered from the hands of nurses and patients in
      an Orthopaedic Hospital. Coliforms were frequently recovered from nurses' hands
      after touching patients' washing materials and clothing as well as after bed
      making, sluice room activities and handling clean or dirty linen and curtains.
      The recovery rates were higher in wards for spinally injured patients than in the
      surgical wards. Coliforms were recovered with similar frequencies, to those from
      nurses, from the hands of patients in both types of wards.

PMID- 1353097
TI  - Rapid genotyping shows the absence of cross-contamination in Enterobacter cloacae
      nosocomial infections.
AB  - Restriction fragment length polymorphism analysis (RFLP) of total DNA and rDNA
      regions was used for the epidemiological evaluation of 10 Enterobacter cloacae
      nosocomial isolates obtained from nine patients in our hospital. Five of these
      patients were hospitalized during overlapping periods, thus raising the question
      of cross-contamination. A single biochemical pattern and antibiotic
      susceptibility profile was observed for all isolates but one. In contrast, based
      on the results of total DNA and rDNA RFLP patterns, the genetic unrelatedness of
      the isolates was clearly shown, thus excluding a common source of contamination
      or patient-to-patient transfer.

PMID- 1353098
TI  - Induction of competence to respond to IL-4 by CD4+ T helper type 1 cells requires
      costimulation.
AB  - Rested murine CD4+ Th1 clones do not produce IL-4, but have previously been shown
      to be capable of responding to IL-4 if they are first activated with Ag and APC.
      In this study, we have examined the activation requirements for induction of
      competence to respond to IL-4 in these clones. TCR occupancy alone (given either
      as chemically fixed APC and Ag, anti-CD3, Con A, or ionomycin and PMA) was
      inadequate, but the addition of a source of costimulation to any of these stimuli
      resulted in complete induction of competence to respond to IL-4. Pretreatment of
      the Th1 clones with TCR occupancy alone induced an anergic state from which
      subsequent full stimulation with Ag and APC failed to give IL-4 responsiveness.
      Pretreatment of the cells with IL-2 alone was an inadequate signal to induce IL-4
      responsiveness and only a partial response was obtained when TCR occupancy was
      combined with IL-2. Addition of anti-IL-2 and anti-IL-2R antibodies during full
      activation with APC and Ag gave a 50% inhibition of competence induction. These
      results demonstrate that costimulation, in addition to its role in IL-2
      production, is an important second signal for inducing T cells to become
      competent to respond to IL-4.

PMID- 1353099
TI  - Immunoregulation in cancer-bearing hosts. Down-regulation of gene expression and
      cytotoxic function in CD8+ T cells.
AB  - The causes of the decreased immune responsiveness in tumor-bearing hosts are
      incompletely understood. The impact of a decreased immune response in cancer
      patients on the clinical response in immunotherapy trials has not been evaluated.
      The present report demonstrates a marked decrease in the therapeutic efficacy of
      adoptively transferred T lymphocytes obtained from murine hosts bearing tumor for
      greater than 30 days [late tumor-bearing mice (TBM)] as compared with normal mice
      and mice bearing tumor for less than 21 days (early TBM). In vitro analysis of
      the functions of the T lymphocytes from late TBM showed an apparently normal
      proliferative response to anti-CD3 and IL-2 with adequate lymphokine production
      from CD4+ cells, but a significant decrease in the cytotoxic function of CD8+
      cells. The decreased cytotoxicity was not because of cell-mediated suppression.
      The expression of granzyme B mRNA was significantly delayed and decreased in
      magnitude in CD8+ cells from late TBM. Culture supernatants from two unrelated
      tumor cell lines were able to inhibit the cytotoxic activity of normal CD8+ cells
      in vitro. The tumor-derived suppressive factor is not transforming growth factor
      beta (TGF-beta), but it has not been further characterized. The data suggest that
      one potential mechanism responsible for immunologic defects in patients with
      large tumor burdens is a tumor-induced defect that compromises the function of
      CD8+ effector T cells.

PMID- 1353100
TI  - Influence of resistant and susceptible genotype, IL-1, and lymphoid organ on
      Trichinella spiralis-induced cytokine secretion.
AB  - The relative importance of cell-mediated inflammatory responses and antibody
      mediated responses in controlling parasitic helminth infection is debated. To
      study the relationship between these responses and resistance or susceptibility
      to primary Trichinella spiralis infection, we infected resistant AKR mice and
      susceptible B10.BR mice and analyzed the lymphokines IL-2, IFN-gamma, and IL-5
      produced by their T cells as a function of time and lymphoid organ. IL-2
      secretors occurred maximally between days 3 and 6 postinfection, whereas IL-5
      secretors peaked between days 6 and 9. Previously, we found that IFN-gamma
      producers peaked before day 6, whereas IL-4 producers peaked between days 6 and
      9. Most cytokine secretors were CD4+. The simultaneous development of IL-2- and
      IFN-gamma-secreting cells, and IL-4- and IL-5-secreting cells, suggests that the
      infection may be stimulating T cells to differentiate into cells capable of
      secreting specific cytokine sets, analogous to the postulated Th1 and Th2
      subsets. In the spleen and mesenteric lymph nodes, cells from B10.BR mice
      secreted more IL-5 than cells from AKR mice, as we found previously for IL-4. For
      both strains, mesenteric lymph node cells produced more IL-5 than splenocytes.
      The AKR mesenteric lymph node cells produced more IL-2 than the B10.BR cells, but
      the reverse occurred in splenocytes. The AKR peripheral lymph node cells also
      secreted more IFN-gamma than the B10.BR cells, but the strains were equivalent
      for peritoneal exudate cell IFN-gamma production. Thus, the lymphoid organ
      microenvironment plays an important role in regulating cytokine-secreting cell
      development in this system. We also tested the possible regulatory role of IL-1.
      Exogenous rIL-1 alpha increased IFN-gamma secretion early but not late in
      mesenteric lymph node cells from both strains; this reflected an increased IFN
      gamma-secreting cell frequency, not a change in IFN-gamma mRNA transcript level.
      Exogenous rIL-1 alpha did not consistently affect IL-2, IL-4, or IL-5 secretion.
      These data suggest that IL-1 alpha availability in vivo may regulate IFN-gamma
      secreting cell development. In sum, early activation of IFN-gamma-secreting T
      cells in lymph nodes, with little subsequent activation of IL-4- and IL-5
      secreting cells, distinguished the resistant from susceptible strain responses to
      T. spiralis infection, and IL-1 alpha and lymphoid organ environment influence
      IFN-gamma-secreting cell activation.

PMID- 1353101
TI  - Cross-linking of sialophorin (CD43) induces neutrophil aggregation in a CD18
      dependent and a CD18-independent way.
AB  - Normal human neutrophils bound an as yet unclustered mAb designated BS-1. The Ag
      immunoprecipitated with BS-1 was blotted by CD43 mAb (and vice versa), and is
      therefore identical to the large sialoglycoprotein. The CD43 Ag expression on the
      neutrophil surface is decreased upon neutrophil activation with the
      chemoattractant FMLP or with PMA. This can be (at least partially) explained by
      the release of CD43+ material with an altered electrophoretic mobility into the
      extracellular medium of the neutrophils upon activation. Cross-linking of the
      CD43 Ag with BS-1 also invoked neutrophil activation by itself: F(ab)2 fragments
      of BS-1-induced neutrophil aggregation, in contrast to F(ab) fragments. Neither
      respiratory burst activity nor a significant rise in intracellular Ca2+ level or
      actin polymerization were observed. The transient neutrophil aggregation response
      was largely CD18 dependent, especially in the initial phase of homotypic
      clustering. However, a significant CD18-independent mechanism contributed
      thereafter to the neutrophil aggregation, as was further substantiated by the use
      of cultured T (and EBV-transformed B) cell clones of a patient with a leukocyte
      adhesion deficiency. CD43 is the first molecule described on neutrophils able to
      induce adhesive properties in a dual fashion.

PMID- 1353102
TI  - Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1
      gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical
      trial. The AIDS Vaccine Clinical Trials Network.
AB  - The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1)
      gp160 recombinant vaccinia virus (HIVAC-1e) vaccine was evaluated in vaccinia
      naive, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n =
      36) were randomized to receive HIVAC-1e or control vaccinia virus at two dosages
      by bifurcated needle puncture at 0 and 2 months; 12 HIVAC-1e and 6 control
      vaccinia virus recipients received either 10(6) or 10(7) pfu/mL at each
      inoculation. There was no significant difference in lesion size, level of viral
      replication, or systemic symptoms after vaccination with HIVAC-1e or control
      vaccinia virus. Of 22 HIVAC-1e recipients with lesion formation, 16 developed low
      titer gp160-specific antibody responses detectable by Western blot. The peak
      response occurred between days 70 and 120 and was still detectable at day 365 in
      9 of 18 vaccinees. gp160-specific lymphoproliferative responses were detected in
      5 of 10 vaccinees. Vaccination with HIVAC-1e was safe in vaccinia-naive, healthy
      adults and could induce both humoral and cell-mediated gp160-specific immune
      responses.

PMID- 1353104
TI  - Human herpesvirus 6 does not enhance human T cell lymphotropic virus type I (HTLV
      I) expression in the HTLV-I-transformed cell line MT4.

PMID- 1353103
TI  - Quantitation of human immunodeficiency virus provirus and circulating virus:
      relationship with immunologic parameters.
AB  - Virologic and seroimmunologic parameters were determined in 56 persons infected
      with human immunodeficiency virus (HIV). The provirus level varied from 10 to
      100,000/10(6) CD4+ lymphocytes, and genomic HIV RNA was detectable in 39 of 56
      patients at a relative concentration varying from 10 to greater than 250
      copies/mL of serum. Provirus expressed as copies per 10(6) CD4+ lymphocytes and
      as circulating virus per milliliter of serum increased with disease progression
      and decrease of CD4+ cell concentration. The mean provirus concentration
      expressed per milliliter of blood varied little among categories of patients with
      various levels of CD4+ cells, but there was a progressive increase of circulating
      HIV genomic RNA. These virologic data suggest that during the course of HIV
      infection, an increasing proportion of the remaining CD4+ lymphocytes harbor the
      HIV genome and produce infectious virus. Finally, there was a marked correlation
      between increased provirus and genomic RNA concentration and three
      seroimmunologic markers: decrease in CD4+ cell count, p24 antigenemia, and
      disappearance of antibodies to HIV core antigen.

PMID- 1353105
TI  - Degenerative changes in the function of neuromuscular junctions of Manduca sexta
      during metamorphosis.
AB  - In Manduca sexta the decline in neuromuscular function during metamorphic
      degeneration was compared in two muscles which differed characteristically with
      regard to pre- and postsynaptic physiological properties. In both muscles,
      morphological evidence indicated that a significant number of the active zones
      within the population of neuromuscular junctions on a given fiber were
      nonfunctional. Nevertheless, the degenerating nerve terminals were able to
      produce an above-threshold excitatory junction potential (EJP) which was
      facilitated in a manner characteristic of the muscle being observed. Abnormal
      findings during the early stages of degeneration included a larger than normal
      EJP, a decline in EJP amplitude over a 20 min period even with low frequencies of
      stimulation, an increase in EJP duration, a decline in muscle fiber resting
      potential amplitude with age, a decrease or disappearance of post-tetanic
      potentiation and long-term facilitation, and an increased likelihood that the
      motor nerve would fail to conduct a stimulus. The two muscles were qualitatively
      similar but quantitatively different with regard to these degenerative changes.
      It is suggested that this combination of relatively normal function with abnormal
      properties might be associated with the withdrawal of glial processes from the
      neuromuscular junctions, changes in the cable properties associated with
      shrivelling of the muscle fibers, and a decline in the metabolic functions
      supporting both muscle fiber resting potentials and those underlying transmitter
      synthesis, mobilization and release.

PMID- 1353106
TI  - Further analysis of nucleic acids in purified scrapie prion preparations by
      improved return refocusing gel electrophoresis.
AB  - Although increasingly unlikely, the possibility of a scrapie-specific nucleic
      acid carried by infectious prion particles is still unresolved. Return refocusing
      gel electrophoresis was developed to detect homogeneous and heterogeneous nucleic
      acids extracted from highly purified scrapie prion preparations. This method was
      improved with respect to the size range from 13 to 1100 nucleotides (nt) over
      which analyses could be performed. The yield of nucleic acid, particularly of
      small DNA oligonucleotides and polyadenylated RNA, was determined after
      deproteinization and two-phase extraction. Despite extensive nuclease digestions
      some small polynucleotides remained. Although a scrapie-specific nucleic acid
      cannot be excluded, the results further define the possible characteristics of a
      hypothetical molecule. If homogeneous in size, such a molecule would be less than
      80 nt in length at a particle-to-infectivity ratio near unity, if heterogeneous,
      scrapie-specific nucleic acids would have to include molecules smaller than 240
      nt.

PMID- 1353107
TI  - Cloning and sequencing of Puumala virus Sotkamo strain S and M RNA segments:
      evidence for strain variation in hantaviruses and expression of the nucleocapsid
      protein.
AB  - The prototype Puumala virus (PV) Sotkamo strain small (S) and medium (M) RNA
      genome segments were amplified by the polymerase chain reaction (PCR), cloned and
      sequenced. The S segment is 1830 nucleotides long with an open reading frame
      coding for 433 amino acids. The identity to the PV Hallnas strain was 83% at the
      nucleotide and 96% at the amino acid level. The M segment in the Sotkamo strain
      is 3616 nucleotides long and contains one open reading frame of 1148 amino acids
      with 83% nucleotide and 94% amino acid identity to the Hallnas strain. Most amino
      acid changes were conservative and the five predicted glycosylation sites are
      identical. The amino acid identity to the prototype hantavirus, Hantaan virus,
      was 62 and 54% for S and M segments, respectively. The coding region of the S
      segment was further amplified by PCR, ligated to pEX vectors and expressed in
      Escherichia coli as a beta-galactosidase fusion protein and was seen to be
      specifically detected by nephropathia epidemica sera in immunoblotting.

PMID- 1353108
TI  - Relationship between HOX2 homeobox gene expression and the human cytomegalovirus
      immediate early genes.
AB  - The human embryonal carcinoma cell line NT2/D1 is known to be non-permissive for
      human cytomegalovirus (HCMV) but becomes permissive after being induced to
      differentiate by retinoic acid (RA). Because homeobox genes have been reported to
      be specifically activated in the RA-differentiated NT2/D1 cells, we investigated
      the possible correlation between expression of homeobox (HOX) 2 genes and
      expression of the immediate early (IE) genes of HCMV both in NT2/D1 cells and in
      HCMV permissive human embryonic lung (HEL) cells. HCMV infection did not induce
      activation of the HOX2A, HOX2E and HOX2I genes in undifferentiated NT2/D1 cells
      nor affect their activation in the RA-differentiated NT2/D1 cells. By in situ
      hybridization using a HOX2A RNA probe, HOX2A transcript-positive cells appeared
      as clusters in RA-differentiated NT2/D1 cells. Viral antigen-positive cells
      detected by immunofluorescence using an antibody specific for the IE-1 antigen of
      HCMV appeared as clusters among the population of cells in which the HOX2A
      transcript was detected. The HOX2A gene only was expressed in HEL cells, however
      none of the HOX2 genes was expressed in non-permissive HeLa, Raji or mouse
      embryonic cells. These results suggest that activation of the HOX2A may be
      necessary for the expression of IE genes. HCMV infection markedly increased the
      expression of the HOX2E gene in HEL cells in the presence, but not in the
      absence, of cycloheximide. Ultraviolet-inactivated HCMV also displayed this
      effect. On the other hand, HCMV infection suppressed expression of the HOX2A gene
      to some degree at the early and late phases of infection in HEL cells. Activation
      of the HOX2E gene by HCMV might possibly have a role in virus-induced abnormal
      embryogenesis.

PMID- 1353109
TI  - Selective inhibition of complex I by N-methylisoquinolinium ion and N-methyl
      1,2,3,4-tetrahydroisoquinoline in isolated mitochondria prepared from mouse
      brain.
AB  - 1,2,3,4-Tetrahydroisoquinoline (TIQ), which is structurally similar to MPTP, has
      been found in human brain and has been reported to inhibit the mitochondrial
      respiration as does 1-methyl-4-phenylpyridinium ion (MPP+). However, the potency
      of inhibition by TIQ is less than that of MPP+. In this study, we report the
      effects of N-methyl-1,2,3,4-tetrahydroisoquinoline (N-Me-TIQ) and N
      methylisoquinolinium ion (N-Me-IQ+) on the mitochondrial electron transport
      system using mitochondria prepared from mouse brains. Five mM N-Me-TIQ and 500
      microM N-Me-IQ+ inhibited complex I activity to 54% and 63% of the control,
      respectively. The IC50 of N-Me-TIQ and N-Me-IQ+ were approximately 6.5 mM and 650
      microM, respectively. Neither substance inhibited complex II, III and IV
      activities. Kinetic analyses of N-Me-IQ+ on complex I activity revealed
      uncompetitive inhibition against NADH and non-competitive inhibition against
      ubiquinone. These inhibitory characteristics were the same to those of MPP+ and
      the inhibitory potency of N-Me-IQ+ on complex I activity was stronger than that
      of MPP+.

PMID- 1353110
TI  - The cardiovascular effects of alpha-receptor blocking agents.
AB  - OBJECTIVE: To characterize selective alpha 1-adrenergic blockers as
      antihypertensive agents, particularly doxazosin. CHARACTERISTICS OF ALPHA
      BLOCKERS: These agents lower elevated blood pressure by reducing peripheral
      arterial resistance without increasing the heart rate or reducing cardiac output.
      They also reduce left ventricular hypertrophy; improve an atherogenic lipid
      profile; reduce the risk of thrombotic complications; reduce the formation of
      fatty streaks, the precursor of advanced athersclerosis; have no adverse
      metabolic effects in diabetic hypertensives; have a comparable side-effect
      profile to that of other antihypertensive drugs; and are cost-effective.
      CONCLUSIONS: In addition to reducing high blood pressure, the alpha-blockers
      reduce a number of other cardiovascular risk factors. In attempts to solve the
      hypertension-coronary dilemma, these additional effects may prove to be of
      crucial importance.

PMID- 1353111
TI  - The case for beta-blockers as first-line antihypertensive therapy.
AB  - REASON FOR TREATMENT: In patients with asymptomatic high blood pressure,
      antihypertensive treatment is initiated for only one reason, to prevent the
      hypertensive sequelae of myocardial infarction, stroke and heart failure.
      MORBIDITY, MORTALITY AND SURROGATE ENDPOINTS: Only diuretics and beta-blockers
      have been shown to benefit hypertensive patients in terms of the hard endpoints
      morbidity and mortality. beta-Blockers and diuretics are cheaper than newer drugs
      and thus represent good value for money. It is not acceptable to use drug effects
      on plasma lipids or insulin resistance as measures of the effects on coronary
      heart disease, since dihydropyridine calcium antagonists improve these parameters
      while significantly increasing coronary heart disease events in the acute and
      chronic ischaemic situation. PATIENT PROFILING: Diuretics. Diuretics appear
      particularly suited to elderly hypertensives, especially those with isolated
      systolic hypertension, but they may increase cardiac events in younger and middle
      aged diabetic and non-diabetic hypertensives. Angiotensin converting enzyme (ACE)
      inhibitors. ACE inhibitors are undoubtedly valuable in the presence of left
      ventricular dysfunction, and possibly in the diabetic in maintaining good renal
      function. beta-Blockers. beta-Blockers are particularly well suited to younger
      and middle-aged hypertensives at all blood pressure levels, especially white
      males; where ischaemia and/or stress is a factor, beta-blockers can significantly
      reduce the incidence of myocardial infarction and strokes. beta-Blockers benefit
      elderly hypertensives by preventing strokes and may prevent coronary heart
      disease if prescribed with a diuretic.

PMID- 1353112
TI  - Thiazide diuretics: first-line therapy for hypertension.
AB  - PURPOSE: To compare low-dose thiazides to beta-blockers, angiotensin converting
      enzyme (ACE) inhibitors, calcium antagonists and alpha-blockers for simplicity,
      tolerability, efficacy, safety and cost-effectiveness as first-line treatment for
      hypertension. METHOD: Review of short-term comparative studies, and the outcome
      of long-term trials with vascular complications of hypertension as endpoints.
      SIMPLICITY: Among the advantages of thiazides are a flat dose-response; no dose
      titration; effectiveness when used once a day; no first-dose hypotension; and few
      contra-indications. TOLERABILITY: Thiazides are the best tolerated agents in
      patients over the age of 60 years and in younger women. They sometimes cause gout
      and impotence in younger men, in whom beta-blockers are equally acceptable first
      line therapy. EFFICACY: Thiazide-based regimens have consistently reduced
      vascular complications of hypertension, the real measure of efficacy. There is
      little evidence that regimens based on other drugs are effective in this sense.
      SAFETY: Concerns that thiazide-induced biochemical changes cause coronary events
      are baseless. An overview of outcome trials shows that thiazide-based treatment
      reduces coronary events significantly, and the reduction is not significantly
      different from that predicted by epidemiological data. Thiazide-based therapy has
      also reduced coronary events significantly and substantially in elderly patients
      with isolated systolic hypertension. COST-EFFECTIVENESS: Low-dose thiazide
      treatment needs minimal monitoring, and has proved most cost-effective in formal
      analyses. CONCLUSION: Low-dose thiazide treatment is a clear first-line choice
      for patients aged over 60 years and younger women, except those with diabetes or
      gout. In younger men there is little to choose between thiazides and beta
      blockers.

PMID- 1353113
TI  - The correct antidote for beta-antagonists.

PMID- 1353114
TI  - [Immunohistochemical study of the human olfactory system].
AB  - Taurine (2-aminoethane sulfonic acid) and carnosine (beta-alanyl-L-histidine) are
      found in large quantities in the olfactory epithelium and bulb. Taurine is a
      structurally simple amino acid, and has been reported to have several putative
      roles, such as neurotransmitter, neuromodulator, neurogrowth factor and to
      function in membrane stabilization. Carnosine, on the other hand, has been
      suggested as a putative neurotransmitter in the olfactory system. We have
      succeeded in visualizing taurine- and carnosine-like immunoreactivities (LI) in
      the human olfactory mucosa, and also carnosine-LI in the human olfactory bulb.
      For this investigation, we collected specimens of the human olfactory bulb by
      autopsy and from the olfactory mucosa by biopsy, and compared localization of
      taurine- and carnosine-LI in several cases. By means of biopsy using Nakano's
      forceps, samples of olfactory mucosa were obtained from 5 cases: a 17 year old
      female, 23 year old male, 46 year old male, 47 year old male, and a 57 year old
      male. The olfactory bulb of a 1 month old male was collected at autopsy. These
      specimens were processed for immunohistochemical study according to the
      peroxidase-antiperoxidase (PAP) method. In the olfactory epithelium, taurine-LI
      was demonstrated in some primary olfactory neurons, and in basal cells. Carnosine
      LI was observed only in primary olfactory neurons, i.e., dendrites, vesicles and
      axonal bundles of olfactory receptor cells, but not in basal cells. In the
      olfactory bulb, the olfactory nerve layer and the glomerular layer showed
      carnosine-LI positive reactions. Therefore, taurine and carnosine may possibly
      coexist in some olfactory neurons. Olfactory receptor cells are classified as
      sensory neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353115
TI  - Dermatopathological aspects of restrictive dermopathy.
AB  - We present an immunopathological and electronmicroscopic study of the skin of two
      newborns affected by restrictive dermopathy. Evidence of abnormal maturation was
      found in the epidermis, cutaneous appendages, dermis, and hypodermis. Our
      observations confirm two previous descriptions. We emphasize some unreported data
      concerning the L1 antigen and Factor XIIIa in the skin. The L1 antigen is
      expressed in the interadnexal epidermis, but not in hair follicles. This is the
      reverse pattern compared with normal skin. Factor XIIIa is poorly expressed in
      dermal dendrocytes, which appear rare compared with controls. The multiple
      defects in maturation found in all cutaneous tissues suggest a qualitative or
      quantitative aberration in control mechanisms of tissue interactions.

PMID- 1353116
TI  - 3-[4-[1-(6-Fluorobenzo[b]thiophen-3-yl)-4-piperazinyl]butyl]- 2,5,5-trimethyl-4
      thiazolidinone: a new atypical antipsychotic agent for the treatment of
      schizophrenia.

PMID- 1353117
TI  - Chronic beta-blockade transregulates inhibitory A1 adenosine and muscarinic M2
      receptors of the adenylyl cyclase system.
AB  - Chronic beta-blockade has evolved to an important therapeutic strategy in
      medicine. Not all its therapeutic effects may be explained by its direct action
      on the beta-adrenergic system. We therefore investigated if chronic beta-blockade
      in vivo or in isolated cell systems may modulate also inhibitory receptors of the
      adenylyl cyclase system. Chronic treatment with metoprolol for 6 days (10 mg/day)
      induced an increase of beta-adrenergic receptors in rat cardiac plasma membranes
      (53 +/- 8 vs 80 +/- 12 fmol/mg protein). Simultaneously the density of cardiac
      muscarinic M2 receptors decreased significantly from 150 +/- 17 to 110 +/- 12
      fmol/mg protein without any change of the affinity of the receptors for their
      agonists or antagonists. By this mechanism chronic beta-blockade leads to an
      unexpected impairment of the muscarinic-mediated inhibition of the adenylyl
      cyclase. This transregulation of inhibitory receptors by chronic beta-blockade
      was not restricted to the heart but also reduced the muscarinic receptors of rat
      lung (35 +/- 4 vs 24 +/- 3 fmol/mg protein). Additionally, other inhibitory
      receptors of the adenylyl cyclase system such as the A1 adenosine receptors of
      rat brain were reduced by chronic beta-blockade (532 +/- 32 vs 444 +/- 26 fmol/mg
      protein). This transregulation of A1 adenosine receptors occurred only after
      chronic beta-blockade with the active stereoisomer (-)-metoprolol whereas the (+)
      isomer was ineffective. The ability of the remaining A1 adenosine receptors to
      form the agonist-promoted high affinity state was unaltered. Their reduction,
      however, was sufficient to abolish the phenylisopropyl-mediated inhibition of the
      adenylyl cyclase. To evaluate if this regulation of various inhibitory receptors
      in different organs may represent a general cellular regulation mechanism, we
      investigated whether this transregulation also occurred in isolated cells.
      Isolated smooth muscle cells derived from the vas deferens (DDT1 MF-2) were
      cultivated in the presence of the beta-blocker atenolol (10(-5) M) for 3 days.
      Chronic beta-blockade in these isolated cells induced an increase of beta
      adrenergic receptors and concomitantly a significant decrease of A1 adenosine
      receptors (460 +/- 42 vs 368 +/- 18 fmol/mg protein). The affinity of the A1
      adenosine receptors for their agonists and antagonists and the ability of the
      remaining receptors to form the agonist-promoted high affinity state remained
      unaltered. In contrast, the reduction of receptor density greatly impaired the
      adenosine-mediated inhibition of the adenylyl cyclase. These data demonstrate
      that chronic beta-blockade leads to a functionally significant reduction of
      inhibitory receptors of the adenylyl cyclase system.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1353118
TI  - A case of simultaneous bilateral nonseminomatous testicular tumors in persistent
      mullerian duct syndrome.
AB  - Persistent mullerian duct syndrome is characteristically associated with
      unilateral or bilateral cryptorchidism. Like other undescended testes, these
      gonads are at an increased risk of malignant transformation. We report a case of
      synchronous bilateral mixed germ cell tumors in the cryptorchid testes of a
      patient with the persistent mullerian duct syndrome.

PMID- 1353119
TI  - Establishment and characterization of doxorubicin-resistant human bladder cancer
      cell line, KK47/ADM.
AB  - A human bladder cancer cell line resistant to doxorubicin, KK47/ADM has been
      established in vitro by exposing KK47 parent cells to progressively higher
      concentrations of the drug over a period of 16 months. The KK47/ADM was 271 times
      more resistant to doxorubicin than the KK47 parent. The KK47/ADM exhibited cross
      resistance to doxorubicin derivatives (pirarubicin, epirubicin), vinca alkaloids
      (vinblastine, vincristine) and etoposide, but not to cisplatin, carboplatin,
      mitomycin C, peplomycin and methotrexate. Unlike the KK47 parent, about 70% of
      the KK47/ADM cells showed a positive reaction with monoclonal antibody against P
      glycoprotein, MRK16. Uptake and efflux studies with [14C]doxorubicin indicated
      that the resistance exhibited by the KK47/ADM line was mainly due to a lower
      accumulation of the drug caused by an increased active efflux, and these were
      reversed in the presence of verapamil. Although verapamil enhanced doxorubicin
      sensitivity of KK47/ADM, a complete overcoming of the resistance could not be
      obtained. These two lines with different chemosensitivity are thus considered to
      be a useful model for developing new chemotherapeutic strategies against
      multidrug resistant bladder cancer.

PMID- 1353120
TI  - [Ganglionic blocking drugs].

PMID- 1353121
TI  - [Alpha-adrenergic receptor blockade].

PMID- 1353122
TI  - [Beta-blockers].

PMID- 1353123
TI  - Nocturnal myoclonus observed in a patient with neuroleptic-induced akathisia.
AB  - An all-night polysomnogram was twice recorded in a patient with neuroleptic
      induced akathisia (NIA). The polysomnogram revealed nocturnal myoclonus. After
      disappearance of akathisia by the administration of clonazepam, we recorded the
      second polysomnogram. At the second examination, sleep efficacy increased and the
      total number of nocturnal myoclonus decreased remarkably. The mean inter-movement
      interval of nocturnal myoclonus prolonged. These findings suggest a close
      relationship between the mechanisms of neuroleptic-induced akathisia and
      nocturnal myoclonus.

PMID- 1353124
TI  - A study of clinical response to different kinds of neuroleptics in first time
      medicated schizophrenics.
AB  - Clinical responses to different kinds of neuroleptics in fresh schizophrenics
      were prospectively investigated. The scales used were the Global Assessment Scale
      (GAS), Brief Psychiatric Rating Scale (BPRS) and Psychiatric Evaluation Scale
      (PES). The 48 subjects were classified into three groups, 16 in the phenothiazine
      response group, 19 in the butyrophenone response group and 13 in the nonresponse
      group. For the schizophrenics who displayed negative symptoms such as motor
      retardation and blunted affect, while displaying milder positive symptoms,
      phenothiazine drugs were effective. Contrarily, for the schizophrenics who
      displayed severe positive symptoms such as hallucination and delusion while
      displaying milder negative symptoms, butyrophenone drugs were effective. Large
      dosages of the drug did not enhance the curative effect in most cases.

PMID- 1353125
TI  - Convulsive seizures in schizophrenic patients induced by zotepine administration.
AB  - One hundred twenty-nine schizophrenic inpatients who were administered zotepine
      were studied to see if they had zotepine-induced convulsive seizures. Twenty-two
      patients had grand mal seizures during the administration periods. The incidence
      of the seizure was 17.1% and was higher than that in previous reports. The
      average duration of zotepine administration before the seizure was 48.3 days. The
      incidence of the seizure was closely related to the daily dosage of zotepine, but
      there was no significant correlation between the daily dosage of zotepine and the
      duration of administration before the onset of the seizure. The patients who
      received a combined administration with the higher dose of zotepine and other
      phenothiazines were revealed to be more likely to have the seizure. In addition,
      young patients and patients with a past history of head injuries showed a high
      incidence of the seizure with the administration of zotepine.

PMID- 1353126
TI  - Voluntary intake of alcohol is attenuated by ipsapirone in mice and role of 5
      HT1A receptor.
AB  - Emerging evidences have suggested that the brain serotonin (5-hydroxytryptamine,
      5-HT) neurotransmitter system is involved in the compulsive alcohol-seeking
      behaviors in humans and animal models. The aim of this study is to examine the
      effect of ipsapirone, which is a specific 5-HT1A agonist with a
      pyrimidinylpiperazine structure, on alcohol consumption in mice (C57BL/6J) by a
      voluntary alcohol intake paradigm. When the consumed alcohol was expressed as
      g/kg B.W., the total 12-day amount was significantly lower in the ipsapirone
      treated mice than in the saline-treated mice. However, 5-HT1A receptor binding
      sites labeled with [3H]8-OH-DPAT in hippocampal membranes did not differ
      significantly in either the total number of binding sites (Bmax) or dissociation
      constant (Kd) between the two groups. The possible mechanism regarding the role
      of ipsapirone that attenuated the alcohol consumption, and its relationship to
      the subtyping 5-HT receptors are further discussed.

PMID- 1353127
TI  - A case of tardive Tourette-like syndrome.
AB  - We have had experience in treating tardive Tourette-like syndrome on a chronic
      schizophrenic patient. The patient was a 38-year-old woman. A diagnosis of
      schizophrenia was made in 1971 and she received repeated medications for 17
      years. In 1989, she began to show vocal tic with coprolalia and motor tic. The
      medications were haloperidol 18 mg, zotepine 200 mg, levomepromazine 100 mg,
      biperiden 3 mg and nitrazepam 10 mg at the beginning of Tourette-like syndrome.
      We have tried to change the medications but this tardive Tourette-like syndrome
      continued to hang on. However, the symptoms gradually improved after a change in
      drugs; cessation of biperiden 3 mg and the administration of clonazepam 3 mg. The
      present case suggested that tardive Tourette-like syndrome might be a subtype of
      neuroleptic-associated tardive syndromes which might be treated with clonazepam.

PMID- 1353128
TI  - Regression in schizophrenia and its therapeutic value.
AB  - Using the regression evaluation scale, 25 schizophrenic patients were classified
      into three groups of Dissolution/autism (DAUG), Dissolution----attachment (DATG)
      and Non-regression (NRG). The regression of DAUG was of the type in which autism
      occurred when destructiveness emerged, while the regression of DATG was of the
      type in which attachment occurred when destructiveness emerged. This suggests
      that the regressive phenomena are an actualized form of the approach complex. In
      order to determine the factors distinguishing these two groups, I investigated
      psychiatric symptoms, mother-child relationships, premorbid personalities and
      therapeutic interventions. I believe that these factors form a continuity in
      which they interrelatedly determine the regressive state. Foremost among them, I
      stressed the importance of the mother-child relationship.

PMID- 1353129
TI  - Acute cyclosporine nephrotoxicity--prototype for a renal membrane signalling
      disorder.

PMID- 1353130
TI  - Reciprocal alterations of GMP reductase and IMP dehydrogenase activities during
      differentiation in HL-60 leukemia cells.
AB  - The study was undertaken to elucidate the regulatory roles of GMP reductase
      (GMPR) and IMP dehydrogenase (IMPDH) on purine interconversion during
      differentiation. Treatment of HL-60 cells with retinoic acid (1 microM) induced
      granulocytic differentiation which was accompanied with a 2.4-fold increase in
      GMPR and 55% decrease in IMPDH activities. Maturation induced by 12-O
      tetradecanoylphorbol 13-acetate or dimethylsulfoxide was also associated with
      similar reciprocal alterations. Incubation with guanosine (200 microM), which
      expands the guanine nucleotide pool, elevated GMPR (1.9-fold) and decreased IMPDH
      (73%) activities. The synchronous and opposing alterations in GMPR and IMPDH
      activities should amplify the metabolic response due to differentiation or
      guanylate pool expansion.

PMID- 1353131
TI  - Induction of CD13 expression on fresh myeloid leukaemia: correlation of CD13
      expression with aminopeptidase-N activity.
AB  - CD13 has proved to be a useful cell surface marker for depicting haematopoietic
      cells of the myeloid and monocytic lineages. Sequence data has shown CD13 to bear
      strong homology to Aminopeptidase-N. Expression of this antigen on myeloid
      leukaemic cells is, however, variable. We have looked at the effects of a phorbol
      ester PMA and a haematopoietic growth factor GM-CSF on the expression of CD13
      displayed by a selected group of myeloid leukaemias at presentation and by normal
      peripheral blood granulocytes. We have found that PMA but not GM-CSF was able to
      stimulate CD13 expression on fresh myeloid leukaemic cells but granulocytes were
      stimulated by either PMA or GM-CSF. In addition, we have correlated CD13
      expression with Aminopeptidase-N enzyme activity on fresh myeloid leukaemic
      cells. These results suggest that CD13 is functionally active on leukaemic cells
      and normal granulocytes.

PMID- 1353132
TI  - Molecular analysis of an ataxia telangiectasia T-cell clone with a chromosomal
      translocation t(14;18)--evidence for a breakpoint in the T-cell receptor delta
      chain gene.
AB  - We established a clonal T-cell line with a reciprocal chromosomal translocation
      t(14;18)(q11;q23) from a patient with ataxia telangiectasia (AT) and T-cell
      chronic lymphocytic leukemia (T-CLL). The tumor cells and the derived T-cell line
      were compared with respect to phenotype, karyotype, and rearrangement pattern.
      Restriction fragment analyses of the T-cell receptor (TCR)-delta gene, which is
      located within the TCR-alpha gene on chromosome 14q11, indicated that the
      breakpoint is located within the TCR-delta locus, splitting the TCR-delta gene
      between the variable and joining segments. This specific chromosomal
      translocation was only detected in the derived T-cell line and may be involved in
      the genesis of T-cell malignancies in AT.

PMID- 1353133
TI  - Nephropathies and exposure to perchloroethylene in dry-cleaners.
AB  - Even in specific risk groups, the relation between exposure to organic solvents
      and chronic renal diseases remains controversial. Thus, in a collaborative
      European study, we assessed the renal effects of occupational exposure to
      perchloroethylene (PCE) in dry-cleaners compared with matched controls who were
      simultaneously examined. Single high and low molecular weight proteins, kidney
      derived antigens and enzymes, and prostanoids were measured in urine. beta 2
      microglobulin, creatinine, laminin fragments, and anti-glomerular basement
      membrane antibodies were also measured in serum. A canonical function based on 23
      such variables correctly classified 93% of individuals as either PCE-exposed or
      controls; with 13 markers, group membership was identified in 87% of subjects.
      Increased high molecular weight protein in urine was frequently (17/50 vs 1/50, p
      less than 0.0001) associated with tubular alterations. Changes were consistent
      with diffuse abnormalities along the nephron in workers exposed to low levels of
      PCE (median 15 parts per million). Generalised membrane disturbances might
      account for the increased release of laminin fragments, fibronectin, and
      glycosaminoglycans, for high molecular weight proteinuria, and for the increased
      shedding of epithelial membrane components from tubular cells with different
      location along the nephron (brush-border antigens and Tamm-Horsfall
      glycoprotein). These findings of early renal changes indicate that solvent
      exposed subjects, especially dry-cleaners, need to be monitored for the possible
      development of chronic renal diseases.

PMID- 1353135
TI  - Clozapine, single photon emission tomography, and the D2 dopamine receptor
      blockade hypothesis of schizophrenia.
AB  - According to the dopamine hypothesis of schizophrenia, D2 receptor blockade is
      essential for a drug to have antipsychotic potency, and antipsychotic potency and
      D2 blockade are linearly related in vitro. To test this assumption in vivo, we
      have compared clinical response with central D2 dopamine receptor availability
      measured by 123I-iodobenzamide single photon emission tomography in two groups of
      schizophrenic patients. 6 patients were on typical antipsychotic drugs and 10
      were on the atypical antipsychotic clozapine, including 2 patients from the first
      group. The patients on typical antipsychotics showed poor therapeutic response
      despite D2 receptor blockade. Significant clinical improvement occurred in all
      patients on clozapine, but at a lower level of D2 blockade by the drug. These
      findings suggest a more complex relation between D2 blockade and clinical
      efficacy than was previously thought.

PMID- 1353134
TI  - Randomised trial of cardiotocography alone or with ST waveform analysis for
      intrapartum monitoring.
AB  - It is possible to record the fetal electrocardiographic waveform (ECG) from the
      scalp electrode used in labour for detection of fetal heart rate. Animal and
      observational studies of changes in the ST waveform of the ECG during hypoxia
      suggest that a combination of heart rate and ST waveform analysis might improve
      the predictive value of intrapartum monitoring. In a randomised trial, we have
      studied intervention rates and neonatal outcome for high-risk labours monitored
      either by conventional cardiotocography (CTG) or by ST waveform analysis plus
      CTG. 1200 women with pregnancy of at least 34 weeks' gestation were assigned to
      the groups when the decision to apply a fetal scalp electrode was made. Neonatal
      outcome was assessed by umbilical-cord blood gas analysis, Apgar scores,
      resuscitation needed, and postnatal course. All recordings were retrospectively
      viewed by an observer unaware of clinical details to check adherence to the trial
      protocol. The addition of ST waveform monitoring to CTG substantially reduced the
      proportion of deliveries for fetal distress (ST + CTG 27/615 vs CTG 58/606; p
      less than 0.001). The groups did not differ in rate of operative delivery for
      other reasons, incidence of asphyxia at birth, or neonatal outcome. Metabolic
      acidosis and low 5 min Apgar scores were less common in the ST + CTG than the CTG
      group, but not significantly so. The only case of birth asphyxia in the ST + CTG
      group was identified by both heart rate and ST changes. The review of recordings
      showed that the reduction in intervention rate was among cases with CTG patterns
      classified as normal or intermediate, whereas there was no difference in
      intervention rates among cases with abnormal recordings. Our findings confirm
      that ST waveform analysis discriminates CTG changes in labour and that our
      protocol for interpretation is safe. Further randomised studies are warranted.

PMID- 1353136
TI  - Improved diagnosis of Pneumocystis carinii infection by polymerase chain reaction
      on induced sputum and blood.
AB  - Detection of Pneumocystis carinii by the polymerase chain reaction (PCR) may
      facilitate non-invasive diagnosis of P carinii pneumonia and study of its
      epidemiology. We have compared the sensitivity and specificity of two PCR methods
      with those of conventional staining for detection of P carinii in induced sputum,
      bronchoalveolar lavage fluid (BAL), and blood. Of 71 sputum samples, 17 were from
      patients with microbiologically confirmed P carinii pneumonia. A nested PCR
      method correctly identified the presence of P carinii in all 17 (100% sensitive,
      95% confidence interval [CI] 81-100%) and found no organisms in 50 of 54
      microbiologically negative samples (93% specific, 95% CI 82-98%). PCR with a
      single primer pair was 71% sensitive (44-90%) and 94% specific (85-99%). The
      sensitivity of conventional staining methods (direct and indirect fluorescence
      antibody and toluidine-blue-O tests) was significantly less (38-53%) than that of
      nested PCR (p less than 0.05). In BAL, neither PCR method was significantly
      better than the conventional staining methods. P carinii was detected in BAL or
      sputum from 10 immunocompromised patients without microbiological evidence of P
      carinii pneumonia, which suggests that symptom-free carriers or subclinical
      infection can exist. P carinii was detected by nested PCR in blood from 2 of 3
      patients with disseminated pneumocystosis but in only 1 of 11 patients with P
      carinii infection restricted to the lungs. Nested PCR on induced sputum is more
      sensitive than conventional staining methods for the diagnosis of P carinii
      pneumonia and provides a non-invasive method of detecting disseminated disease.

PMID- 1353137
TI  - Effect of stereotactic thalamic lesion on essential tremor.
AB  - The cause of essential (low-frequency) tremor is unknown and its relation to
      physiological (high-frequency) tremor is unclear. We assessed essential tremor in
      one patient before and after a stereotactic thalamic lesion. The procedure
      changed the size of the tremor in the right hand but not in the left. Persistence
      of a low-frequency component suggested that essential tremor was an additional
      feature superimposed on physiological tremor in this patient. The focus of
      essential tremor seems to be an autonomous central generator that is independent
      of physiological tremor mechanisms.

PMID- 1353138
TI  - CD8 lymphocytosis and pseudotumoral splenomegaly in HIV infection.
AB  - Three patients infected with human immunodeficiency virus (HIV) presented with
      pseudotumoral splenomegaly, CD8 lymphocytosis (3.5-5.1 x 10(9)/l), and
      hypergammaglobulinaemia. Spleen and bone marrow showed diffuse CD8 lymphocyte and
      plasma-cell infiltration. Amplification of the T-cell-receptor gamma chain gene
      did not reveal any clonal T-cell population. Phenotypic analysis showed a
      predominance of CD8/CD57 suppressor T cells with expression of activation markers
      (DR and CD38). No cytotoxic T lymphocytes specific for HIV could be detected. The
      three patients shared the HLA haplotype A1, B8, DR3. The association with this
      haplotype suggests a genetically determined host immune response to HIV.

PMID- 1353139
TI  - Screening for cystic fibrosis.

PMID- 1353140
TI  - Colorectal cancer: new evidence for the adenoma/carcinoma sequence.

PMID- 1353142
TI  - Negative investigations.

PMID- 1353141
TI  - Multipurpose spermicides.

PMID- 1353143
TI  - Prenatal screening for cystic fibrosis.
AB  - Screening for carriers of CF (cystic fibrosis) is now possible but the best way
      of delivering such a service is unknown. In one model 4348 women attending
      antenatal clinics in an Edinburgh maternity hospital were invited to participate
      in a trial of prenatal screening. Mouthwash samples were tested for six CF
      alleles (85% of mutant genes) and when a woman was found to be a CF carrier her
      partner was also tested. Heterozygous couples were offered prenatal diagnosis.
      609 (14%) women declined to enter the trial and another 574 (13%) were not
      screened, usually because of late booking. Among the remaining 3165 women there
      were 111 carriers of a CF gene (1 in 29). 4 of these 111 had carrier partners and
      these couples opted for prenatal diagnosis, the 1 pregnancy with an affected
      fetus being terminated. The psychological impact of screening was assessed by the
      general health questionnaire. There was a significant increase in stress at the
      time of the test result among women identified as carriers. However, this
      disappeared when their male partners tested normal and did not reappear later in
      the pregnancy. By providing time for couples to discuss the possibility of
      screening and by offering the test at a point (the antenatal booking clinic) at
      which most pregnant women are seen, this approach has advantages, provided that
      counselling is readily available.

PMID- 1353144
TI  - Psychological and social consequences of community carrier screening programme
      for cystic fibrosis.
AB  - We have assessed the effect of screening for cystic fibrosis (CF) carrier status
      on anxiety levels, attitudes, knowledge and actions of participants in a pilot
      programme conducted through primary health care services. Over 3000 individuals
      were screened and 100 carriers with no previous family history were identified.
      Varying degrees of anxiety were found to be associated initially with a positive
      result, but most of this was allayed by genetic counselling, and we find no
      adverse long-term psychological consequences in carriers. Most discussed carrier
      status with their partner (89%), parents, other relatives and also with friends;
      87% of partners to whom testing was suggested have been screened. Those testing
      positive indicated that knowledge of carrier status would be considered in future
      reproductive decisions, and after 6 months carriers retained a reasonable level
      of knowledge about CF and its inheritance. Carriers and non-carriers uniformly
      approve of screening and are glad to have been tested. Knowledge of CF in the
      sample of non-carriers has also increased after testing, suggesting screening may
      improve understanding of CF among the entire target population. Fears of possible
      social costs of screening may be ill-founded.

PMID- 1353145
TI  - Thrombolytic therapy for patients with myocardial infarction presenting after six
      hours.

PMID- 1353146
TI  - Healing rituals and sacred serpents.
AB  - Votive tablets found during the excavation of shrines of the Graeco-Roman god of
      medicine (Asklepios or Aesculapius) associate the healing of superficial lesions
      with contact with the oral cavity of non-poisonous serpents. We suggest that this
      may have been the empirical exploitation of the healing properties of salivary
      growth factors. By immunohistochemistry and immunoblotting we demonstrate the
      expression of the epidermal growth factor and its receptor in the oral, upper
      digestive, and salivary epithelia of Elaphe quatuorlineata, a species probably
      used in healing rituals.

PMID- 1353147
TI  - Tobacco litigation (USA, UK, and Australia).

PMID- 1353148
TI  - Oxidised LDL and progression of atherosclerosis.

PMID- 1353149
TI  - Oxidised LDL and progression of atherosclerosis.

PMID- 1353150
TI  - Oxidised LDL and progression of atherosclerosis.

PMID- 1353151
TI  - Air emboli in human donor liver.

PMID- 1353152
TI  - Factor XII deficiency and central retinal vein occlusion.

PMID- 1353153
TI  - Prenatal diagnosis of myotonic dystrophy by direct mutation analysis.

PMID- 1353154
TI  - Detection of minimum mutation carriers in myotonic dystrophy.

PMID- 1353156
TI  - Partogram presentation and obstetric decision-making.

PMID- 1353155
TI  - Clarithromycin and omeprazole for Helicobacter pylori.

PMID- 1353158
TI  - Value of the obstetric partogram.

PMID- 1353157
TI  - Pseudohemiparetic parkinsonism.

PMID- 1353159
TI  - Endometriosis and spontaneous rupture of utero-ovarian vessels during pregnancy.

PMID- 1353160
TI  - Bioavailability of interleukin-2 after reconstitution with albumin.

PMID- 1353161
TI  - Cold chain deficiencies in Central Asian Republics.

PMID- 1353162
TI  - Health of the Nation.

PMID- 1353163
TI  - Cost of sumatriptan.

PMID- 1353164
TI  - Euthanasia.

PMID- 1353165
TI  - Citation of original research.

PMID- 1353166
TI  - Episodic arthritis in cystic fibrosis.

PMID- 1353167
TI  - Hepatitis A vaccination.

PMID- 1353168
TI  - Crossreactions between Legionella and Campylobacter spp.

PMID- 1353170
TI  - Axillary node dissection in breast cancer.

PMID- 1353169
TI  - Emerging quinolone resistance in campylobacters.

PMID- 1353171
TI  - Axillary nodes dissection in breast cancer.

PMID- 1353172
TI  - Axillary nodes dissection in breast cancer.

PMID- 1353173
TI  - Axillary nodes dissection in breast cancer.

PMID- 1353174
TI  - Axillary nodes dissection in breast cancer.

PMID- 1353175
TI  - Axillary nodes dissection in breast cancer.

PMID- 1353176
TI  - Bristol Cancer Help Centre.

PMID- 1353177
TI  - IUDs and pelvic inflammatory disease.

PMID- 1353178
TI  - Evaluation of anti-HCV capsid indeterminate serum samples.

PMID- 1353179
TI  - Detection of HCV in seronegative donors with raised ALT.

PMID- 1353180
TI  - Persistence of antibodies to Trypanosoma brucei gambiense after treatment of
      human trypanosomiasis in Uganda.

PMID- 1353181
TI  - African trypanosomiasis: more aggressive treatment or more aggressive research?

PMID- 1353182
TI  - Eosinophilia, clozapine, and pancreatitis.

PMID- 1353183
TI  - Hepatic injury associated with itraconazole.

PMID- 1353184
TI  - Loss of taste and terbinafine.

PMID- 1353185
TI  - Immunisation of infants in Iceland against Haemophilus influenzae type b.

PMID- 1353186
TI  - Factor VIII inhibitors in haemophiliacs.

PMID- 1353187
TI  - Loss of red-green colour vision after exposure to arc light.

PMID- 1353188
TI  - Safety of roxithromycin.

PMID- 1353189
TI  - Modulation of multidrug-resistant multiple myeloma by cyclosporin. The Leukaemia
      Group of the EORTC and the HOVON.
AB  - Resistance to chemotherapy in refractory multiple myeloma is frequently
      associated with expression of multidrug resistance (MDR). In resistant cells,
      intracellular accumulation of doxorubicin and vincristine does not occur because
      the MDR-1 gene product, a membrane glycoprotein (PgP), is an energy-dependent
      efflux pump. Cyclosporin is one of several non-cytotoxic drugs that can block the
      function of PgP. In a prospective study, we assessed the possibility that
      cyclosporin could be used clinically to modulate MDR. We studied 21 patients with
      multiple myeloma; disease had progressed during primary chemotherapy in 6 and was
      resistant to VAD (vincristine, doxorubicin, dexamethasone) in 15. The patients
      received cyclosporin by continuous infusion during VAD treatment; there were
      three cyclosporin dosage groups (5, 7.5, 10 mg/kg daily). Serum cyclosporin
      concentrations adequate for MDR modulation were reached in all patients receiving
      7.5 or 10 mg/kg daily. 47% (7) of the VAD-refractory patients and 48% (10) of the
      whole group responded to VAD. Before treatment, MDR-1 expression was present in
      12 patients. After VAD plus cyclosporin, no MDR-1-positive plasma cells were
      present in 6 of 8 patients tested. The response rate in MDR-1-positive patients
      was 58% compared with 33% in all our patients. Toxic effects were mild and
      reversible and did not include nephrotoxic or serious cardiovascular side
      effects. 12 months after the start of treatment, survival was 85%, and disease
      free survival at a median of 9 months after the response was 65%. Thus, in
      multiple myeloma clinical resistance to VAD can be circumvented by cyclosporin,
      which enables the cytotoxic drugs to eliminate resistant myeloma cells.

PMID- 1353190
TI  - Abnormal expression of wild type p53 protein in normal cells of a cancer family
      patient.
AB  - Mutations in the p53 gene are the commonest specific genetic change in human
      cancer. In normal tissues, p53 protein is present in such low quantities that it
      is not readily detectable by immunochemical techniques. However, in many tumour
      cells large amounts of p53 protein accumulate and can be seen by simple
      immunohistochemical staining; this is generally attributed to the accumulation of
      stabilised, mutant protein. We have found a mother and daughter, who both have a
      history of breast cancer, who show strong immunohistochemical staining of p53 in
      most of their normal epithelial and mesenchymal cells. Their family has a history
      of multiple cancers developing at an early age. Detailed protein analysis and
      gene sequencing of material obtained from cultured cells, grown from a skin
      biopsy taken from the daughter, suggest that her cells contained large quantities
      of normal (unmutated) p53. We suggest that this phenotype defines a new inherited
      cancer susceptibility syndrome that is distinct from the germ-line mutations in
      p53 found in some Li-Fraumeni families. This new syndrome affects p53 tumour
      suppressor function through an indirect mechanism that stabilises normal p53. It
      remains to be established whether this mechanism also contributes to the
      accumulation of p53 in sporadic cancers.

PMID- 1353191
TI  - Growth hormone response to clonidine in central and peripheral primary autonomic
      failure.
AB  - Patients with primary autonomic failure may have either pure autonomic failure
      (PAF) or multiple system atrophy (MSA) in which there is additional neurological
      involvement. Distinction between PAF and MSA at an early stage is important
      because a wide range of complications is associated with MSA, which has a poor
      response to drug therapy and a less favourable prognosis. We have investigated
      the growth hormone (GH) releasing effects of clonidine in patients with PAF and
      MSA to see whether this hormonal response could serve as a neuroendocrine marker
      to distinguish between the groups. Age-matched normal subjects were studied as
      controls. Both groups of patients had severe postural hypotension due to primary
      sympathetic failure of presumed central origin in MSA and peripheral origin in
      PAF. After clonidine, plasma GH concentrations increased in controls and PAF,
      with no change in MSA. Changes in plasma glucose and insulin concentrations were
      similar in all groups. Clonidine, therefore, stimulates growth hormone release in
      PAF but not MSA and may serve as a neuroendocrine marker in differentiating
      patients with MSA and a central autonomic defect from those with PAF with a
      peripheral defect.

PMID- 1353193
TI  - Simian immunodeficiency virus needlestick accident in a laboratory worker.
AB  - The macaque monkey infected with simian immunodeficiency virus (SIV) is an animal
      model of the acquired immunodeficiency syndrome. We investigated a laboratory
      worker who was exposed by needlestick accident to blood from an SIV-infected
      macaque. Seroreactivity to SIV developed within 3 months of exposure, with
      antibody titres peaking from the third to the fifth month and declining
      thereafter. Polymerase chain reaction for SIV sequences and cultures of
      peripheral-blood mononuclear cells failed to show infection. Inoculation of an
      SIV-negative monkey with blood from the worker did not cause infection. Animal
      care and laboratory workers should adhere strictly to recommended procedures to
      avoid accidental exposures when working with SIV-infected animals or specimens.

PMID- 1353192
TI  - Vitamin A supplementation and child survival.
AB  - Previous studies of the effect of 6-monthly vitamin A supplementation on child
      mortality have given conflicting results. In other trials, more frequent doses of
      vitamin A have significantly reduced mortality among children at risk of vitamin
      A deficiency. We have done a double-blind, placebo-controlled trial of vitamin A
      supplementation in the Sudan among 28,753 children aged 9-72 months at risk of
      vitamin A deficiency. Children were assigned to receive either 200,000 IU vitamin
      A and 40 IU vitamin E every 6 months (vitamin A group) or 40 IU vitamin E alone
      (placebo group). During the 18 months of follow-up, there were 120 deaths
      (8.4/1000) in the vitamin A group and 112 (7.9/1000) in the placebo group
      (relative risk 1.06, 95% confidence interval 0.82-1.37). Controlling for
      geographic site, round of observation, anthropometry, morbidity, dietary intake
      of vitamin A, sex, and all baseline differences between the two groups did not
      change the results. Children living in poor and unsanitary environments, younger
      children, and those sick, stunted, wasted, or consuming diets low in vitamin A
      were at a significantly higher risk of dying. The lack of an effect of large-dose
      vitamin A supplementation on mortality, despite a clear association between
      dietary vitamin A and mortality, underscores the need to identify factors that
      modify the efficacy of vitamin A supplements as a public-health measure. Reducing
      poverty, improvements in sanitation, and access to adequate diets should remain
      the main goals to improve child survival.

PMID- 1353194
TI  - Acquired immunodeficiency without evidence of infection with human
      immunodeficiency virus types 1 and 2.
AB  - There have been three published cases of acquired immunodeficiency in which no
      evidence for infection with human immunodeficiency virus (HIV) types 1 and 2 was
      found. We have identified five other individuals, from the New York City area
      (four who have known risk factors for HIV infection), with profound CD4 depletion
      and clinical syndromes consistent with definitions of the acquired
      immunodeficiency syndrome (AIDS) or AIDS-related complex. None had evidence of
      HIV-1, 2 infection, as judged by multiple serologies over several years, standard
      viral co-cultures for HIV p24 Gag antigen, and proviral DNA amplification by
      polymerase chain reaction.

PMID- 1353195
TI  - Trimming hedges.

PMID- 1353196
TI  - Stapled anastomoses and colon cancer recurrence.

PMID- 1353197
TI  - Specialist medical training and the EC: secrets are edged tools.

PMID- 1353198
TI  - Pyridinium crosslinks as markers of bone resorption.

PMID- 1353199
TI  - Cricket under stress.

PMID- 1353200
TI  - AIDS minus HIV?

PMID- 1353201
TI  - Seasonal cryptogenic organising pneumonia with biochemical cholestasis: a new
      clinical entity.
AB  - The term cryptogenic organising pneumonia has been used for the combination of
      dyspnoea, cough, pleuritic pain, widespread shadows on chest radiographs, and
      histological evidence of intra-alveolar organisation with buds of granulation
      tissue within the alveoli. We report 12 patients with seasonal recurrence of this
      disorder for between 3 and 11 years. In all 12 patients, symptoms recurred
      between late February and early May every year, tending to increase in severity
      each year, and resolved between June and January. Chest radiography and computed
      tomography showed bilateral consolidation. Lung biopsy samples showed intra
      alveolar buds of granulation tissue. There were many neutrophils within the
      lumina of medium-sized airways and terminal bronchioles showed evidence of
      obstruction by granulation tissue. Functionally, the predominant defect was
      restrictive and only 2 patients (life-long non-smokers) had airflow limitation.
      All 12 patients had very high activities of liver enzymes, suggesting
      intrahepatic cholestasis, but no other evidence of liver disease. Cultures of
      blood, sputum, lung tissue, and bronchoalveolar lavage fluid, viral screening,
      and complement fixation tests were consistently negative. In all patients all
      abnormalities responded rapidly to oral steroid therapy. These findings suggest a
      seasonal syndrome of organising pneumonia and biochemical abnormalities
      indicative of intrahepatic cholestasis. No aetiological factor has been
      identified, but the nature and periodicity of the illness point to an inhaled
      agent present in the environment for a limited period every year.

PMID- 1353203
TI  - A fresh look at the atherogenic remnant hypothesis.

PMID- 1353202
TI  - Treatment of small hepatocellular carcinomas.
AB  - There is growing interest in screening to detect symptomless hepatocellular
      carcinoma (HCC), which should be easier to treat than symptomatic tumours.
      Combined alpha-fetoprotein and ultrasound monitoring can detect HCCs of 1 cm, and
      Lipiodol retention can be detected in tumours smaller than 1 cm. A number of
      treatment options are available. Surgical resection may be curative in selected
      patients with a single small tumour, but the cirrhotic patient is left with a
      diseased liver and the risk of tumour recurrence or death from underlying liver
      dysfunction. Orthotopic liver transplantation is a rational treatment for
      patients with decompensating cirrhosis and a small HCC, but it is expensive and
      necessitates immunosuppression. A variety of targeted or local therapies, either
      individually or in combination, can be used to treat HCC. These include
      percutaneous alcohol injection into an HCC, which may be an alternative to
      surgical resection. Tumour necrosis can be seen after targeted Lipiodol
      chemotherapy or radiotherapy. Transcatheter arterial embolisation selectively
      embolises the feeding artery, and can be combined with Lipiodol chemotherapy.
      Small tumours are thus amenable to treatment, even in patients who cannot have
      surgery. Screening and treatment for symptomless HCC seems justified, unless
      controlled trials teach us differently.

PMID- 1353204
TI  - Margaret Thatcher's tobacco temptation.

PMID- 1353205
TI  - Right to refuse treatment.

PMID- 1353206
TI  - Human insulin and hypoglycaemia.

PMID- 1353207
TI  - Human insulin and hypoglycaemia.

PMID- 1353208
TI  - Human insulin and hypoglycaemia.

PMID- 1353209
TI  - Botulism and Guillain-Barre syndrome.

PMID- 1353210
TI  - Autoantibodies in pet dogs of patients with systemic lupus erythematosus.

PMID- 1353211
TI  - Misoprostol-associated fever in cirrhotic patient.

PMID- 1353212
TI  - Adult Schonlein-Henoch purpura after enalapril.

PMID- 1353213
TI  - Hyperpyrexia induced by 3,4-methylenedioxyamphetamine ("Eve")

PMID- 1353214
TI  - Transmission of hepatitis C with pasteurised factor VIII.

PMID- 1353215
TI  - Migration of "endo-clips" into common bile-duct after laparoscopic
      cholecystectomy.

PMID- 1353216
TI  - Cutaneous anthrax due to penicillin-resistant Bacillus anthracis transmitted by
      an insect bite.

PMID- 1353217
TI  - Prediction of outcome in fulminant hepatic failure by serum human hepatocyte
      growth factor.

PMID- 1353218
TI  - Costs of medline and CD-ROM searching.

PMID- 1353219
TI  - Epidemiology in central and eastern Europe.

PMID- 1353220
TI  - Audit and research.

PMID- 1353221
TI  - Banking umbilical cord blood.

PMID- 1353222
TI  - Natural family planning in developing countries.

PMID- 1353223
TI  - Mefloquine prophylaxis against malaria for female travellers of childbearing age.

PMID- 1353224
TI  - Treatment of primaquine-resistant Plasmodium vivax malaria.

PMID- 1353225
TI  - Responsiveness of chronic pain to morphine.

PMID- 1353226
TI  - Responsiveness of chronic pain to morphine.

PMID- 1353227
TI  - Stapling device for vaginal hysterectomy.

PMID- 1353228
TI  - Which heparin for proximal deep-vein thrombosis?

PMID- 1353229
TI  - Oestrogen and progesterone receptor status in breast cancer and development of
      endometrial abnormalities.

PMID- 1353230
TI  - Radiotherapy and ductal carcinoma-in-situ of breast.

PMID- 1353231
TI  - Wine and coronary heart disease.

PMID- 1353232
TI  - Wine and coronary heart disease.

PMID- 1353233
TI  - Wine and coronary heart disease.

PMID- 1353234
TI  - Wine and coronary heart disease.

PMID- 1353236
TI  - "Herd immunity" and the meningococcal vaccine trial in Norway.

PMID- 1353235
TI  - Wine and coronary heart disease.

PMID- 1353237
TI  - Pathogenesis of Crohn's disease.

PMID- 1353238
TI  - Leukoencephalopathy in children with t(1;19) acute lymphoblastic leukaemia.

PMID- 1353239
TI  - Sustained haematological response to high-dose oral alfacalcidol in patients with
      myelodysplastic syndromes.

PMID- 1353240
TI  - Serum cholesterol and long-term death rates from suicide, accidents, or violence.
      Seven Countries Study Group.

PMID- 1353241
TI  - Clinical outcome of Borrelia burgdorferi related dilated cardiomyopathy after
      antibiotic treatment.

PMID- 1353242
TI  - Alga or bacterium?

PMID- 1353243
TI  - Autonomic neuropathy and prolongation of QT-interval in liver disease.

PMID- 1353244
TI  - Supersensitivity of sigma receptors after repeated administration of cocaine.
AB  - We investigated the role of sigma receptors in the expression of behavioral
      sensitization induced by cocaine. Rats received intraperitoneal injections of
      either 20 mg/kg cocaine or saline once daily for 14 consecutive days. Cocaine
      treated rats became sensitized. After a 5-day abstinence period, a challenge dose
      of (+)-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine ((+)-3-PPP), a sigma receptor
      agonist, was administered. (+)-3-PPP at doses of 12 and 24 mg/kg induced
      significantly more frequent rearing and more potent stereotypy consisting of
      repetitive head movement and sniffing in cocaine-sensitized rats than in saline
      pretreated rats. These enhanced responses to (+)-3-PPP lasted for at least a
      month. The enhanced responses to (+)-3-PPP were attenuated by 30 mg/kg BMY 14802,
      a putative sigma antagonist, and also attenuated by 100 mg/kg (+/-)-sulpiride, a
      D2 dopamine antagonist. These findings show that repeated administration of
      cocaine produces lasting supersensitivity of simga receptors, which may induce
      subsequent activation of dopaminergic transmission.

PMID- 1353245
TI  - Drugs that cause sexual dysfunction: an update.

PMID- 1353246
TI  - Unexplained CD4+ T-lymphocyte depletion in persons without evident HIV infection-
      United States.
AB  - Since 1989, 21 persons with unexplained CD4+ T-lymphocyte depletion, but without
      evident human immunodeficiency virus (HIV) infection, have been described (1-12).
      These reports included persons who have resided in the United States and six
      other countries and who sought medical care for conditions often associated with
      immune deficiency. Some of these cases were also described at the VII
      International Conference on AIDS/III STD World Congress in Amsterdam. In
      addition, CDC has received reports of five persons from three states who have had
      persistently low CD4+ T-cell levels but who have had no evidence of HIV infection
      or underlying disease processes or therapies known to be associated with T-cell
      depletion. In some of these five patients, opportunistic infections were
      diagnosed that frequently occur in persons with acquired immunodeficiency
      syndrome (AIDS). This report describes preliminary clinical and laboratory
      findings from an ongoing investigation by CDC of these five patients.

PMID- 1353247
TI  - Pharmacological characteristics of alpha 2-adrenergic receptors: comparison of
      pharmacologically defined subtypes with subtypes identified by molecular cloning.
AB  - On the basis of extensive radioligand data and more limited functional data,
      three pharmacological subtypes of alpha 2-adrenergic receptors have been
      identified. More recently, three human genes or cDNAs for alpha 2-adrenergic
      receptors have been identified by molecular cloning. The relationship, however,
      among the pharmacologically defined subtypes and those identified by molecular
      cloning has not been clear. In order to resolve this issue, we have compared the
      pharmacological characteristics of the receptors identified by molecular cloning
      and expressed in COS-7 cells with the characteristics of the pharmacologically
      defined receptors in their respective prototypic tissue or cell line. The
      affinities (Ki values) of 12 subtype-selective alpha 2-adrenergic antagonists
      were determined for the alpha 2 receptor in the six preparations, by radioligand
      binding. Correlation analyses of the pKi values indicate that the alpha 2A
      subtype, as defined in the HT29 cell line, the alpha 2B receptor of the neonatal
      rat lung, and the alpha 2C subtype, as defined in an oppossum kidney cell line,
      correspond to the cloned human alpha 2-C10, alpha 2-C2, and alpha 2-C4 receptor
      subtypes, respectively.

PMID- 1353248
TI  - Up-regulation of N-methyl-D-aspartate receptors on cultured cortical neurons
      after exposure to antagonists.
AB  - The density of N-methyl-D-aspartate (NMDA) receptors on membranes prepared from
      cultured cortical neurons was determined using binding assays with [125I]I-MK-801
      after exposure of cultures to antagonists of the NMDA receptor complex. The
      density of binding sites for [125I]I-MK-801 was increased by 40-80% after
      exposure to D-2-amino-5-phosphonopentanoic acid (D-AP5), with no change in the
      number or viability of neurons. The effect of D-AP5 was concentration dependent,
      with an EC50 of 10 microM. Up-regulation of NMDA receptors was observed after 2-7
      days but not after 1 day of exposure to 100 microM D-AP5. The density of NMDA
      receptors was also increased after exposure of cells to CGS 19755 and MK-801 but
      not after exposure to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. The
      binding of [3H]AMPA was unaltered after exposure to D-AP5. These results
      demonstrate that the density of NMDA receptors on cultured neurons can be
      selectively up-regulated by exposure to NMDA receptor antagonists. Increases in
      the density of NMDA receptors occurring in vivo could complicate therapeutic
      approaches to the treatment of neurological disorders.

PMID- 1353249
TI  - Cloning of two mouse genes encoding alpha 2-adrenergic receptor subtypes and
      identification of a single amino acid in the mouse alpha 2-C10 homolog
      responsible for an interspecies variation in antagonist binding.
AB  - Molecular cloning and ligand binding studies have shown the alpha 2 class of
      adrenergic receptor (alpha 2-AR) to be a family of at least three related
      subtypes in humans. These studies have not, however, identified distinct subtype
      specific functions for these receptors in vivo. It should be possible to extend
      the analysis of alpha 2-AR subtype function to the animal level through the use
      of experimental mammalian embryology in mice. To begin this process, we have
      isolated two mouse genomic clones encoding alpha 2-AR subtypes and expressed
      these genes in COS-7 cells for binding studies. Sequence homology and ligand
      binding data allow the assignment of one clone (M alpha 2-4H) as the mouse
      homolog of the human alpha 2-C4 subtype. The other clone (M alpha 2-10H) closely
      resembles the human alpha 2-C10 subtype in sequence but binds with significantly
      lower affinity to yohimbine and rauwolscine, members of a distinct class of bulky
      alpha 2-selective antagonists commonly used to evaluate alpha 2-AR function in
      vivo. To define the domain(s) responsible for this unusual binding property, we
      constructed a series of M alpha 2-10H/human alpha 2-C10 chimeric receptors.
      Analysis of these receptors identified a conservative Cys201 to Ser201 change in
      the fifth transmembrane domain of M alpha 2-10H as being responsible for the low
      affinity of the mouse receptor for yohimbine.

PMID- 1353250
TI  - Pharmacological properties of two cloned somatostatin receptors.
AB  - Previous studies have shown that at least two subtypes of somatostatin (SRIF)
      receptors (SRIF1 and SRIF2) are expressed in mammalian cells. SRIF1 receptors
      have high affinity for MK 678, whereas SRIF2 receptors have no affinity for MK
      678 but selectively bind peptides with structures similar to that of CGP 23996.
      Recently, two SRIF receptor genes have been cloned from human and mouse genomic
      libraries. In the present study, the pharmacological properties of these two
      cloned SRIF receptors, expressed in Chinese hamster ovary (CHO) cells, were
      investigated, to determine whether they have any similarity to the previously
      described SRIF1 and SRIF2 receptor subtypes. Both cloned receptors could be
      labeled with 125I-Tyr11-SRIF and exhibited high affinity for SRIF. The SSTR1
      receptor could also bind CGP 23996-like compounds but not MK 678. In contrast,
      the SSTR2 receptor was insensitive to CGP 23996-like compounds but bound MK 678
      with high affinity. These findings indicate that the peptide specificities of the
      cloned SSTR1 and SSTR2 receptors differ from each other. Pretreatment of CHO
      cells expressing the two cloned SRIF receptors with SRIF abolished high affinity
      agonist binding to the cloned SSTR2 receptor but not the cloned SSTR1 receptor.
      Agonist binding to SSTR1 receptors was not significantly affected by guanosine-5'
      )-(3-thiotriphosphate) or pertussis toxin pretreatment, whereas agonist binding
      to SSTR2 receptors was inhibited by both treatments. These findings suggest that
      SSTR2 receptors can be regulated and they associate with pertussis toxin
      sensitive guanine nucleotide-binding proteins, whereas SSTR1 receptors do not.
      SRIF is a potent inhibitor of adenylyl cyclase activity in mammalian cells.
      However, neither the cloned SSTR2 nor SSTR1 receptor mediated SRIF inhibition of
      adenylyl cyclase activity in stably transformed CHO cells or COS-1 cells
      transiently expressing the cloned receptors, suggesting that neither cloned
      receptor couples to adenylyl cyclase. The results of these studies indicate that
      the two cloned SRIF receptors have different pharmacological properties. The
      characteristics of the cloned SSTR2 receptor are similar to those of the
      previously described SRIF1 receptor, and the characteristics of the cloned SSTR1
      receptor are similar to those of the previously described SRIF2 receptor.

PMID- 1353251
TI  - Expression of c-fos in human and murine multidrug-resistant cells.
AB  - In both mouse sarcoma 180 and human KB cells selected for the multiple drug
      resistance (MDR) phenotype, there is an elevation in the steady state mRNA level
      of c-fos. There is no detectable gene amplification for c-fos, nor is there any
      significant change in the rate of mRNA transcription or degradation, suggesting
      that other factors are responsible for the increased expression level in
      resistance. Cells selected for resistance to methotrexate, a drug not in the MDR
      group, do not have an increase in c-fos mRNA expression. When drug-sensitive
      cells are exposed for 30 min to an ED50 concentration of vinblastine, Adriamycin,
      colchicine, or VP-16, but not to methotrexate or cisplatin, there is a 3-6-fold
      induction in the level of c-fos message. Because the former drugs are members of
      the MDR class and the latter are not, the results are consistent with the
      hypothesis that induction of c-fos by low levels of cytotoxic drugs may be an
      early event in the acquisition of the MDR phenotype. If this were the case, then
      c-fos would be expected to act in concert with c-jun to control transcription by
      binding to a specific DNA regulatory site. Consistent with this explanation is
      the existence of an AP-1 sequence in the promotor region for the P-glycoprotein
      gene (mdr1), as well as the fact that c-jun is also overexpressed in MDR cells.

PMID- 1353252
TI  - Persistent paralysis in critically ill patients after long-term administration of
      vecuronium.
AB  - BACKGROUND: The muscle relaxant vecuronium is sometimes administered to
      facilitate mechanical ventilation. Neuromuscular paralysis lasting up to seven
      days may occur after the termination of long-term administration (i.e., more than
      two days) of vecuronium in critically ill patients. We investigated the role of
      clinical factors and plasma concentrations of vecuronium and its metabolite in
      causing this prolonged neuromuscular blockade. METHODS: We studied 16 critically
      ill adult patients (8 women and 8 men) who had received vecuronium to facilitate
      mechanical ventilation for at least two consecutive days. Clinical factors and
      plasma concentrations of vecuronium and 3-desacetylvecuronium, the active
      metabolite of vecuronium, were compared in patients with and without prolonged
      neuromuscular blockade. In addition, we performed detailed pharmacokinetic
      studies in the patients without prolonged neuromuscular blockade. RESULTS: Seven
      of the 16 patients had prolonged neuromuscular blockade, lasting from six hours
      to more than seven days, after the termination of vecuronium therapy. These seven
      patients, six of whom were women, had higher plasma magnesium concentrations and
      lower arterial blood pH values than the nine patients without prolonged
      neuromuscular blockade. They also had higher plasma concentrations of 3
      desacetylvecuronium and a higher frequency of renal failure (seven of seven
      patients vs. four of nine patients, P less than 0.03). In the patients without
      prolonged neuromuscular blockade, the mean (+/- SD) plasma clearance, elimination
      half-life, and volume of distribution of vecuronium were 2.5 +/- 1.0 ml per
      kilogram of body weight per minute, 299 +/- 154 minutes, and 1.1 +/- 0.6 liters
      per kilogram, respectively. CONCLUSIONS: Prolonged neuromuscular blockade after
      the termination of long-term treatment with vecuronium is associated with
      metabolic acidosis, elevated plasma magnesium concentrations, female sex, and
      probably more important, the presence of renal failure and high plasma
      concentrations of 3-desacetylvecuronium.

PMID- 1353253
TI  - Mutual interaction of histamine H3-receptors and alpha 2-adrenoceptors on
      noradrenergic terminals in mouse and rat brain cortex.
AB  - Brain cortex slices were preincubated with 3H-noradrenaline and superfused with
      physiological salt solution containing desipramine. We studied the inhibition of
      the electrically evoked tritium overflow caused by histamine in the presence of
      alpha-adrenoceptor ligands (mouse and rat brain cortex), and the inhibition
      caused by talipexole (the former B-HT 920) in the presence of H3-receptor ligands
      (mouse brain cortex). In mouse brain cortex slices, the inhibitory effect of
      histamine on the tritium overflow evoked by 36 pulses, 0.3 Hz was not changed by
      the alpha 1-adrenoceptor antagonist prazosin, but increased by the alpha 2
      adrenoceptor antagonist rauwolscine. When the current strength or the duration of
      electrical pulses was reduced to compensate for the increase in evoked tritium
      overflow produced by rauwolscine, the latter still enhanced the effect of
      histamine. The histamine-induced inhibition of tritium overflow evoked by 360
      pulses, 3 Hz was not affected by the alpha 1-adrenoceptor agonist phenylephrine
      but attenuated by the alpha 2-adrenoceptor agonist talipexole. Finally, the
      inhibition by histamine of the tritium overflow evoked by 3 pulses, 100 Hz was
      attenuated by talipexole but not affected by rauwolscine. Conversely, the
      inhibitory effect of talipexole on tritium overflow elicited by 360 pulses, 3 Hz
      was slightly attenuated by the H3-receptor agonist R-(-)-alpha-methylhistamine
      but not affected by the H3-receptor antagonist thioperamide. In rat brain cortex
      slices, histamine only tended to inhibit tritium overflow evoked by 360 pulses, 3
      Hz, both in the absence of alpha-adrenoceptor antagonists and in the presence of
      prazosin. However, histamine markedly inhibited the evoked overflow in the
      presence of rauwolscine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353255
TI  - [Changes in somatosensory evoked potentials in pharmacogenic myoclonia].
AB  - Transient increases of the early cortical somatosensory evoked potentials (SSEP)
      were observed in 9 patients who received antidepressant and/or neuroleptic
      treatment. All patients developed myoclonus, and 2 had grand mal seizures. Three
      cases--one 20-, one 17- and one 15-year-old patient--are presented in detail.
      Similar observations have been reported in elderly patients. Possible underlying
      mechanisms and the potential value of the SSEP in identifying and monitoring
      patients at risk of developing psychotropic drug-induced side-effects are briefly
      discussed.

PMID- 1353254
TI  - Alpha 2-autoreceptor-mediated modulation of tyrosine hydroxylase activity in
      noradrenergic regions of the rat brain in vivo.
AB  - The physiological importance of brain alpha 2-adrenoceptors in controlling the
      activity of tyrosine hydroxylase in noradrenergic regions was investigated using
      the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after decarboxylase
      inhibition as a measure of the rate of tyrosine hydroxylation (and synthesis of
      noradrenaline) in vivo. In the hypothalamus and cerebral cortex, clonidine (0.025
      1 mg/kg, i.p.) decreased (18%-43%) and idazoxan (0.1-80 mg/kg, i.p.) increased
      (20%-73%) the synthesis of DOPA in a dose-dependent manner. Moreover,
      pretreatment with idazoxan (0.1 mg/kg) antagonized the effect of clonidine (0.1
      mg/kg) in the hypothalamus. After treatment with reserpine (5 mg/kg, s.c., 18 h
      before decapitation) and depletion of noradrenaline, clonidine (0.5 mg/kg)
      continued to decrease (50%-55%) but idazoxan (20 mg/kg) failed to increase the
      synthesis of DOPA, which suggested the involvement of an alpha-auto-receptor
      mechanism. Acute treatments of rats (not exposed to reserpine) with a wide
      variety of adrenoceptor agonists such as guanfacine 6, B-HT920, xylazine,
      bromoxidine (1 mg/kg) and antagonists such as yohimbine, phentolamine, prazosin
      (10 or 20 mg/kg) resulted in significant decreases (15%-55%) or increases (21%
      99%) in the synthesis of DOPA in both brain regions. However, other agonists
      (oxymetazoline, azepexole, tramazoline, methoxamine) and antagonists (tolazoline,
      dihydroergotamine, phenoxybenzamine, propranolol) did not modify the synthesis of
      DOPA. In the hypothalamus and cerebral cortex the effects of the drugs were
      consistent with the selectivity of alpha-adrenoceptor agonists and antagonists
      (except prazosin) for an alpha 2-adrenoceptor. The results also suggest that the
      alpha 2-autoreceptor that modulates the synthesis of noradrenaline in the rat
      brain appears to belong to the prazosin-sensitive alpha 2B-subtype.

PMID- 1353256
TI  - L-glutamate inhibition of an inward potassium current in neonatal neurons from
      the nucleus of the solitary tract.
AB  - Neurons isolated from the nucleus of the solitary tract (NTS) of 1- to 4-day-old
      rats were cultured for a study of the glutamatergic responses in this region of
      the medulla. Whole cell currents were examined under voltage clamp after 6-14
      days in culture. An inwardly rectifying potassium current was identified in
      107/174 cells. The presence of this K+ current diminished with time in culture
      from greater than 80% of the cells at day 6 to less than 30% of the cells after
      day 10. The current was inhibited by L-glutamate (IC50 = 10 microM).

PMID- 1353257
TI  - MK-801, a non-competitive antagonist of NMDA receptor, prevents methamphetamine
      induced decrease of striatal dopamine uptake sites in the rat striatum.
AB  - We investigated the effects of MK-801, a non-competitive antagonist of NMDA
      receptor, on methamphetamine-induced decrease in dopamine (DA) uptake sites in
      the rat striatum. Repeated administrations of an escalating dose of
      methamphetamine (2.5, 5, 7.5, 10 mg/kg s.c. x2, every other day for a week)
      produced decreased DA uptake sites assayed by binding with [3H]GBR 12935 in the
      striatum. Co-administration of MK-801 and methamphetamine significantly prevented
      the methamphetamine-induced decrease in striatal [3H]GBR 12935 binding.
      Administration of MK-801 alone did not affect [3H]GBR 12935 binding. These
      results suggest that some neurochemical effects of methamphetamine may be
      mediated via mechanism involving excitatory amino acids.

PMID- 1353258
TI  - Studies on the origin of rat hippocampal dihydroxyphenylacetic acid using
      microdialysis.
AB  - With a dialysis probe implanted in the rat ventral hippocampus we have monitored
      effects on noradrenaline (NA) and dihydroxyphenylacetic acid (DOPAC) of the
      infusion through the dialysis probe of drugs acting at dopaminergic and
      noradrenergic presynaptic autoreceptors; clonidine and idazoxan produced changes
      in the extracellular concentration of both NA and DOPAC, whereas LY171555 and
      sulpiride had no effect on NA but produced changes in the concentration of DOPAC.
      The combined effect of clonidine and LY171555 on DOPAC was additive. Hippocampal
      DOPAC is therefore derived from both the noradrenergic and the dopaminergic
      projection to the hippocampus.

PMID- 1353259
TI  - Receptor-coupled uptake of valproate in rat astroglial primary cultures.
AB  - Various receptor ligands were investigated for their effects on the uptake of the
      antiepileptic drug valproic acid (VPA) in primary astroglial cultures from
      cerebral cortex of neonatal rats. After stimulation with the alpha 1-adrenoceptor
      agonist phenylephrine, 5-hydroxytryptamine (5-HT) or the glutamate receptor
      agonists glutamate, quisqualate and kainate, the Vmax and Km values for the drug
      transport increased. On the contrary, after exposure to the alpha 2-adrenoceptor
      agonist clonidine, Vmax and Km decreased. The effects were reversed in comparison
      to the control level in the presence of selective receptor antagonists. The data
      indicate a specific coupling between receptors and the uptake system for VPA.
      Furthermore, the results may have significant implications, as they suggest that
      receptors on astrocytes can be involved in the local regulation of drug transport
      in brain.

PMID- 1353260
TI  - Cardiovascular responses to feeding in newborn piglets.
AB  - Cardiovascular responses to feeding have been observed in several species during
      various periods of development and have been implicated in the development of
      cardiovascular regulation. In the rat, these responses are characterized by short
      lasting, large increases in blood pressure (BP) and moderate increases in heart
      rate. These responses appear to be sympathetically mediated because pretreatment
      with ganglionic blockers eliminates the increase in BP associated with milk
      ingestion. The present study was designed to determine if similar cardiovascular
      responses occur during feeding in the newborn piglet. Piglets were obtained on
      postnatal d 2 and fed a milk diet via automatic feeder 6 times a day. On
      postnatal d 6, the piglets were instrumented with an external carotid artery
      catheter and an internal jugular vein catheter. On postnatal d 8 and 9, direct
      arterial BP and heart rate were recorded during feeding. BP responses to milk
      ingestion were immediate, and they reached a maximum increase of 50% above
      baseline on both test days and followed a response profile similar to that
      previously described in the 15-d-old rat. An increase in heart rate was also
      observed, reaching a maximum of 42% above baseline. The results show that early
      in life piglets have large cardiovascular responses to milk ingestion similar to
      those observed in young rats and human infants. These responses appear to model
      the cardiovascular responses to feeding observed in human infants and might be
      useful as a noninvasive method for assessing neonatal autonomic reactivity. These
      responses also have the potential to cause adverse effects in newborns already at
      risk for cardiovascular and cerebrovascular disease.

PMID- 1353261
TI  - Conference report: IVth meeting of European Placenta Group (EPG): joint with the
      Rochester Trophoblast Conference (RTC), 22-26 September 1991.

PMID- 1353262
TI  - Synthesis and histamine H2-receptor activity of heterocyclic impromidine
      analogues.
AB  - Analogues of the H2-agonist impromidine with unsubstituted or substituted
      aromatic or non-aromatic heterocycles instead of the 5-methylimidazole group were
      prepared via the benzoylguanidine method and tested for H2-agonistic and H1
      antagonistic activity in the guinea-pig isolated right atrium and ileum,
      respectively. Compounds with unsubstituted 2- or 3-pyridyl, 2-pyrazinyl, or 5
      pyrimidyl thioether portion proved to be about equipotent in the atrium (about 2
      4x histamine). Highest potency was found in the 5-chloro-3
      pyridylthioethylguanidine 8h, that is about 20 times more potent as an H2-agonist
      than histamine, corresponding to about 8 times the activity of the unsubstituted
      parent compound 8g. It is demonstrated by the piperidinyl- and morpholinylalkyl
      guanidines 8m-o that an aromatic ring is not required in the affinity-conferring
      moiety of H2-agonists (8n: 1.3x histamine). Replacement of the (5-methylimidazol
      4-yl)methylthio group in the H2-antagonist cimetidine by halogenated pyridyl,
      pyrazinyl and pyrimidinyl thioethers resulted in compounds inactive as H2
      antagonists, giving further evidence for differences in the structural
      requirements of the affinity-conferring portions of H2-agonists and antagonists
      and their mode of interaction with the receptor protein.

PMID- 1353263
TI  - Age-dependent choice of sexual partners and the transmission dynamics of HIV in
      Sub-Saharan Africa.
AB  - A mathematical model of the transmission of HIV-1 within heterosexual populations
      in Sub-Saharan Africa is described and its properties analysed. The model
      incorporates epidemiological and demographic processes and extends previous work
      in this area via the inclusion of age and sex dependency in rates of sexual
      partner change, and sexual partner choice dependent on age. Parameter assignments
      are made on the basis of current data on the transmission dynamics of HIV-1 and
      the demography of human populations in Africa. Both age-dependent rates of sexual
      activity and the sexual contact of males with females younger than themselves act
      to enhance the predicted demographic impact. With realistic parameter values, the
      model suggests AIDS is able to reverse the sign of population growth rates from
      positive to negative values over a timescale of a few decades. The sensitivity of
      this prediction is examined in relation to changes in the pattern of sexual
      contact between different age classes of females and males, different patterns of
      change in the age-dependent rate of sexual partner change, different assumptions
      concerning the doubling time of the epidemic in its early stages, and the
      relative efficiencies of viral transmission between men and women, and vice
      versa. The impact AIDS is predicted to have on the number of young and elderly
      persons as a fraction of the number of productive adults (the dependancy ratio)
      is examined under various assumptions concerning the weighting to be applied to
      mirror the burden imposed by the care of those with AIDS. The paper includes an
      assessment of the influence of the timing of changes in sexual behaviour, or the
      promotion of the use of condoms, on the predicted course of the epidemic. The
      paper concludes with a discussion of data needs and the model refinements
      required to more accurately mirror current understanding of the epidemiology of
      HIV-1.

PMID- 1353264
TI  - Cholinergic interneurons in the feeding system of the pond snail Lymnaea
      stagnalis. I. Cholinergic receptors on feeding neurons.
AB  - All the identified feeding motoneurons of Lymnaea respond to bath or
      iontophoretically applied acetylcholine (ACh). Three kinds of receptors (one
      excitatory, one fast inhibitory and one slow inhibitory) were distinguished
      pharmacologically. The agonist TMA (tetramethylammonium) activates all three
      receptors, being weakest at the slow inhibitory receptor. PTMA
      (phenyltrimethylammonium) is less potent than TMA and is ineffective at the slow
      inhibitory receptor, which is the only receptor sensitive to arecoline. At 0.5 mM
      the antagonists HMT (hexamethonium) and ATR (atropine) selectively block the
      excitatory response, while PTMA reduces the response to ACh at all three
      receptors. d-TC (curare) antagonizes only the fast excitatory and the fast
      inhibitory responses, but MeXCh (methylxylocholine) blocks the fast excitatory
      and slow inhibitory responses solely. For each of the feeding motoneurons, the
      sign of the cholinergic response (excitation or inhibition) is the same as the
      synaptic input received in the N1 phase of the feeding rhythm.

PMID- 1353266
TI  - Cholinergic interneurons in the feeding system of the pond snail Lymnaea
      stagnalis. III. Pharmacological dissection of the feeding rhythm.
AB  - The feeding activity of the pond snail Lymnaea stagnalis was stimulated by
      depolarization of a modulatory interneuron (SO) or of a N1 pattern-generating
      interneuron. The cholinergic antagonists phenyltrimethylammonium (PTMA),
      methylxylocholine (MeXCh), hexamethonium (HMT) and atropine (ATR) were applied at
      0.5 mM in the bath and their effects on the rhythmic feeding pattern were
      monitored. Each of the antagonists slowed or blocked the feeding rhythm. The
      block was due to interference in the pattern generating network, not to
      disturbance of modulatory inputs. The experimental results favour a model in
      which the alternation of protraction (N1) and retraction (N2) phases occurs by
      recurrent inhibition. The results would be more difficult to explain on the
      reciprocal inhibition model. When all the N1 output was blocked, the N1 neurons
      fired rhythmic bursts endogenously.

PMID- 1353265
TI  - Cholinergic interneurons in the feeding system of the pond snail Lymnaea
      stagnalis. II. N1 interneurons make cholinergic synapses with feeding
      motoneurons.
AB  - The N1 neurons are a population of interneurons active during the protraction
      phase of the feeding rhythm. All the N1 neurons are coupled by electrical
      synapses which persist in a high Mg/low Ca saline which blocks chemical synapses.
      Individual N1 spikes produce discrete electrotonic postsynaptic potentials (PSPS)
      in other N1 cells, but the coupling is not strong enough to ensure 1:1 firing.
      Bursts of N1 spikes generate compound PSPS in the feeding motoneurons. The sign
      (excitation or inhibition) of the N1 input corresponds with the synaptic barrage
      recorded during the protraction phase. Discrete PSPS are only resolved in a Hi-Di
      saline. Their variation in latency and number can be explained by variation in
      electrotonic propagation within the electrically coupled network of N1 cells. The
      excitatory postsynaptic potentials (ESPS) in the 1 cell are reduced by 0.5 mM
      antagonists hexamethonium (HMT), atropine (ATR), curare (d-TC) and by
      methylxylocholine (MeXCh), all of which block the excitatory cholinergic receptor
      (Elliott et al. (Phil. Trans. R. Soc. Lond. 336, 157-166 (Preceding paper.)
      (1992)). The 1 cell EPSPS were transiently blocked by phenyltrimethylammonium
      (PTMA), which is both an agonist and antagonist at the 1 cell excitatory
      acetylcholine (ACh) receptor (Elliott et al. 1992). The inhibitory postsynaptic
      potential (IPSP) in the 3 cell is blocked by bath applications of MeXCh and PTMA,
      which both abolish the response of the 3 cell to ACh (Elliott et. al. 1992). The
      effects of the cholinergic antagonists on the response of 4 cluster and 5 cells
      to N1 stimulation matches their response to ACh (Elliott et al. 1992). It is
      concluded that the population of N1 cells are multiaction, premotor cholinergic
      interneurons.

PMID- 1353267
TI  - Cerebellar cortex: its simulation and the relevance of Marr's theory.
AB  - Marr's theory of the cerebellar cortex as an associative learning device is one
      of the best examples of a theory that directly relates the function of a neural
      system to its neural structure. However, although he assigned a precise function
      to each of the identified cell types of the cerebellar cortex, many of the
      crucial aspects of the implementation of his theory remained unspecified. We
      attempted to resolve these difficulties by constructing a computer simulation
      which contained a direct representation of the 13,000 mossy fibres and the
      200,000 granule cells associated with a single Purkinje cell of the cerebellar
      cortex, together with the supporting Golgi, basket and stellate cells. In this
      paper we present a detailed explanation of Marr's theory based upon an analogy
      between Marr's cerebellar model and an abstract model called the associative net.
      Although some of Marr's assumptions contravene neuroanatomical findings, we found
      that in general terms his conclusion that each Purkinje cell can learn to respond
      to a large number of different patterns of activity in the mossy fibres is
      substantially correct. However, we found that this system has a lower capacity
      and acts more stochastically than he envisaged. The biologically realistic
      simulated structure that we designed can be used to assess the computational
      capabilities of other network theories of the cerebellum.

PMID- 1353268
TI  - Modelling mechanically stable muscle architectures.
AB  - This paper presents a planar architectural model for an activated skeletal
      muscle, with mechanical equilibrium throughout the muscle belly. The model can
      predict the shape of the muscle fibres and tendinous sheets as well as the
      internal pressure distribution in the central longitudinal plane (perpendicular
      to the tendinous sheets) of uni- and bipennate muscle bellies. Mechanically
      stable solutions for muscle architectures were calculated by equating the
      pressure developed by curved muscle fibres with the pressure under a curved
      tendinous sheet. The pressure distribution under a tendinous sheet is determined
      by its tension, its curvature and the tensile stress of the attached muscle
      fibres. Dissections showed a good resemblance of the architecture of embalmed
      muscles with those from our simulations. Calculated maximum pressures are in the
      same order of magnitude as pressure measurements from the literature. Our model
      predicts that intramuscular blood flow can be blocked during sustained
      contraction, as several experimental studies have indeed demonstrated. The volume
      fractions of muscle fibres and interfibre space in the muscle belly were also
      calculated. The planar models predict a too low volume fraction for the muscle
      fibres (about 45% for the bipennate models with a straight central aponeurosis,
      and about 60% for the simulated unipennate muscle). It is discussed how, in a
      real muscle, this volume problem can be solved by a special three-dimensional
      arrangement of muscle fibres in combination with varying widths of the tendinous
      sheets.

PMID- 1353269
TI  - [Neuroleptic malignant syndrome--a case report].
AB  - The occurrence of a malignant neuroleptic syndromes accompanied by urinary
      retention under the treatment with fluphenazine and prothipendyl in a mentally
      disabled psychotic is reported. Early recognition of the syndrome and immediate
      termination of the neuroleptic treatment lead to its spontaneous remission.
      Subsequent neuroleptic treatment by clozapine was tolerated without further
      complications.

PMID- 1353271
TI  - 4th Asian-Pacific Congress of Nephrology (continued). Beijing, People's Republic
      of China, October 15-20, 1990. Abstracts.

PMID- 1353270
TI  - Diseases of the adrenal medulla.

PMID- 1353272
TI  - Urodynamic evaluation of patients following spinal cord injury.

PMID- 1353273
TI  - Nitric oxide: first in a new class of neurotransmitters.

PMID- 1353274
TI  - Effects of the novel NMDA receptor antagonist, CGP 39551, on field potentials and
      the induction and expression of LTP in the dentate gyrus in vivo.
AB  - The effects of the novel competitive N-methyl-D-aspartate (NMDA) receptor
      antagonist, CGP 39551 [the carboxyethylester of CGP 37849; DL-(E)-2-amino-4
      methyl-5-phosphono-3-pentenoic acid], on extracellular field potentials and long
      term potentiation (LTP) induced in the dentate gyrus by stimulation of the
      perforant path were studied in anesthetized rats. CGP 39551 attenuated the
      population spike (PS) and excitatory postsynaptic potential (EPSP) amplitude of
      dentate field potentials, reduced the NMDA receptor-mediated component of train
      evoked burst potentials, and prevented the induction of LTP. The decrease in PS
      and EPSP amplitude produced by CGP 39551 was observed mainly in non-potentiated
      synaptic populations; potentiated field potentials were only minimally affected
      by drug treatment. These results are consistent with receptors may contribute in
      a tonic manner to the state of dentate granule cell excitability. Finally, the
      differential modulation of potentiated and non-potentiated synapses by CGP 39551
      suggests that a change in some properties of postsynaptic AMPA receptors is
      involved in the expression of LTP.

PMID- 1353275
TI  - GABAB receptor-mediated inhibitory postsynaptic potentials evoked by electrical
      stimulation and by glutamate stimulation of interneurons in stratum lacunosum
      moleculare in hippocampal CA1 pyramidal cells in vitro.
AB  - Following micropressure application of glutamate (500 microM) in stratum
      lacunosum-moleculare (L-M), inhibitory postsynaptic potentials (glut-IPSPs) were
      recorded in CA1 pyramidal cells. These glut-IPSPs were blocked by tetrodotoxin (1
      microM) and, thus, were probably generated by the activation of local
      interneurons. The effects of pharmacological antagonists on glut-IPSPs and on
      electrically-evoked early and late IPSPs were assessed in the same cells during
      the same application of the antagonist. Local application of the GABAB antagonist
      2-OH saclofen (1-4 mM) reduced both glut-IPSPs and late IPSPs but not early
      IPSPs. In contrast, the GABAB antagonist phaclofen (20 mM) reduced late IPSPs but
      not early IPSPs but not early IPSPs or glut-IPSPs. Early IPSPs were blocked by
      the GABAA antagonists bicuculline and picrotoxin but late IPSPs and glut-IPSPs
      were not. Repetitive electrical stimulation depressed early and late IPSPs as
      well as glut-IPSPs, suggesting that interneurons activated with glutamate were
      also stimulated electrically. Thus, interneurons in str. lacunosum-moleculare
      appear to inhibit pyramidal cells via a GABAB receptor-mediated IPSP. The
      discrepancy in the pharmacological profile of the GABAB glut-IPSPs and of the
      GABAB late IPSPs may suggest the presence of two GABAB mechanisms in CA1
      pyramidal cells.

PMID- 1353276
TI  - Changes in extracellular glutamate concentration produced in the rat striatum by
      repeated ischemia.
AB  - BACKGROUND AND PURPOSE: Evidence suggesting that ischemia-induced neuronal damage
      may be linked to an extracellular overflow of glutamate has accumulated, and
      previous studies have shown that repetitive ischemic insults may have a
      cumulative effect. The purpose of this study was to investigate changes in the
      extracellular glutamate concentration produced by repeated brief ischemic
      episodes of varied severity. METHODS: Four consecutive 3- or 5-minute periods of
      bilateral hemispheric ischemia were produced in rats, each ischemic period
      followed by 27 minutes of reperfusion. Extracellular glutamate in the striatum
      was monitored using microdialysis, and the electroencephalogram and extracellular
      direct current potential were recorded in the same tissue site to assess the
      severity of ischemia. RESULTS: The results suggest that the kinetics of the
      increase in the extracellular glutamate concentration produced by a brief
      ischemic episode are similar, irrespective of whether it is a single insult or
      part of a repeated sequence. In all cases, the extracellular glutamate
      concentration increased throughout ischemia and returned to its preischemic level
      early during reperfusion. The pattern of changes in the ischemia-induced
      glutamate overflow during repetitive insults varied with the severity of
      ischemia, in common with the pattern of changes in the direct current potential,
      supporting the concept that ionic changes associated with anoxic depolarization
      are a major determinant of ischemia-induced glutamate overflow. CONCLUSIONS:
      There may be no cumulative effect of brief repeated episodes of ischemia on the
      extracellular glutamate concentration, even though repeated 5-minute ischemic
      episodes apparently caused progressive deterioration of ionic homeostasis in some
      cases.

PMID- 1353277
TI  - Catecholamine synthesizing enzymes in 70 cases of functioning and non-functioning
      phaeochromocytoma and extra-adrenal paraganglioma.
AB  - Immunohistochemical localization of the catecholamine synthesizing enzymes,
      tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), dopamine
      beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT), was
      investigated in 70 cases of functioning and non-functioning phaeochromocytomas
      comprising 52 of adrenal and 18 of extra-adrenal origin. Of 59 functioning
      tumours, 30 were mixed epinephrine and norepinephrine-producing (mixed type) and
      29 were norepinephrine-producing tumours. TH, AADC and DBH were detected in all
      functioning phaeochromocytomas, but PNMT was limited to the mixed-type
      phaeochromocytomas. Non-functioning phaeochromocytomas were divided into two
      groups, comprising a complete type, which induced neither elevated plasma
      catecholamines nor their metabolites in urine, and an incomplete type which
      exhibited no elevated plasma catecholamines, but showed a slightly high urinary
      vanillylmandelic acid level. In the non-functioning complete-type tumours,
      immunoreactive TH was negative, but the incomplete tumours of the adrenal medulla
      had all four enzymes, and corresponded to a mixed-type phaeochromocytoma. AADC
      and DBH were present universally in all functioning and non-functioning tumours,
      including TH-negative tumours. TH is a rate-limiting enzyme of catecholamine
      biosynthesis and deficiency of TH is an important feature of extra-adrenal non
      functioning phaeochromocytomas.

PMID- 1353278
TI  - [New, in Austria registered specialty drugs. Hivid (2',3'-dideoxycytidine; ddC)].

PMID- 1353280
TI  - Wound Healing of the Ocular Surface. The 8th Paulo Foundation International
      Medical Symposium. Helsinki, August 1991.

PMID- 1353281
TI  - Interaction between the middle ear and the inner ear. Proceedings of 4th
      International Academic Otologic Workshop. Umea, Sweden. August 26-28, 1990.

PMID- 1353279
TI  - Immunohistochemical study of kuru plaques using antibodies against synthetic
      prion protein peptides.
AB  - Prion protein (PrP) is a protein closely associated with the transmission of
      scrapie and Creutzfeldt-Jakob disease (CJD). Kuru plaques are composed of this
      protein. PrP33-35 is converted to protease-resistant PrP27-30 by proteinase K
      digestion. It has not yet been determined which of these PrPs is present in kuru
      plaques in vivo. Accordingly we synthesized two peptides (peptide-N and peptide
      M) that, respectively, corresponded to the protease-sensitive and protease
      resistant portions of PrP33-35, based on the amino acid sequence deduced from
      human PrP cDNA. These two synthetic peptides were used to immunize rabbits and
      produce antisera (anti-N and anti-M). Both antisera stained kuru plaques in a
      patient with Gerstmann-Straussler syndrome and one with CJD. Peptide-N has an
      amino acid sequence which does not exist in PrP27-30. Staining of kuru plaques by
      the antiserum against peptide-N indicated that the entire molecule, including the
      N-terminal portion of PrP33-35, was deposited in the kuru plaques.

PMID- 1353282
TI  - Beta-agonists and surfactant in eustachian tube function.
AB  - The presence of surface tension lowering substances (surfactants) is demonstrable
      in the Eustachian tube (ET) and the middle ear, both in animals and in humans. In
      the lungs, beta-adrenoceptor agonists stimulate the secretion of surfactant; and
      it has been suggested that beta-agonists have a similar effect both in the ET and
      the middle ear, because opening of the ET is facilitated by the non-selective
      beta-agonist, isoprenaline in the rat, and by the beta 2-agonist, terbutaline, in
      humans. Two studies are described: In one, children with otitis media with
      effusion took terbutaline or placebo twice a day for two weeks and no significant
      differences were found between the effects of the two treatments; in the other
      study, it was shown that surfactant markedly facilitated the opening of the
      Eustachian tube. Lung surfactant prepared from pigs and instilled as a single
      dose into the middle ear of healthy rats reduced the air pressure necessary to
      open the Eustachian tube by as much as 15-20% for as long as the experiments
      lasted (i.e., around one hour). Thus, possibilities of facilitating the opening
      of the Eustachian tube do in fact exist.

PMID- 1353283
TI  - Cue exposure and learning theory.
AB  - The implications are discussed for cue exposure treatment of four theoretical
      issues; (a) spontaneous recovery, (b) response competition, (c) generalization,
      and (d) the cognitive basis of conditioning. It is suggested that practical cue
      exposure treatment will not be as straight-forward as initial trials have
      suggested.

PMID- 1353284
TI  - Neurobiology of Essential Fatty Acids. Proceedings of a symposium. Palm Cove, Far
      North Queensland, Australia, July 10-12, 1991.

PMID- 1353286
TI  - Long chain omega 3 polyunsaturates in formula-fed term infants.

PMID- 1353285
TI  - Modulation of glutamate release from hippocampal mossy fiber nerve endings by
      arachidonic acid and eicosanoids.
AB  - Arachidonic acid has been implicated in normal synaptic transmission processes,
      including those related to the development of hippocampal long-term synaptic
      potentiation. Hippocampal mossy fiber (MF) synaptosomes were used to investigate
      the role of arachidonate in the evoked accumulation of presynaptic Ca2+ and the
      release of endogenous glutamate, since these nerve terminals express long-term
      potentiation and selectively release glutamate as the excitatory transmitter. It
      was demonstrated that membrane depolarization evoked the accumulation of Ca2+,
      the release of glutamate, and the production of unesterified arachidonic acid.
      These events may be functionally related, since exogenous arachidonate and
      phospholipase A2 activation mimicked the effects of depolarization on Ca2+
      availability and glutamate release, while secretion processes were attenuated in
      the presence of phospholipase A2 inhibitors. In addition, pretreatment of the
      nerve terminals with arachidonate or melittin allowed for the facilitated release
      of glutamate in response to a subsequent depolarizing stimulus. Inhibition of
      cyclooxygenase or lipoxygenase activities also potentiated presynaptic responses
      to membrane depolarization. In contrast, 12-lipoxygenase products attenuated the
      depolarization-evoked accumulation of intraterminal free Ca2+ and glutamate
      release. It is suggested that arachidonic acid acts as a positive modulator of
      mossy fiber secretion processes, including those involved in the increased
      glutamate release required for the induction of long-term potentiation, while 12
      lipoxygenase metabolites provide negative feedback signals designed to limit
      neurotransmitter secretion.

PMID- 1353287
TI  - Reciprocal regulation of fatty acid release in the brain by GABA and glutamate.
AB  - Several model systems have been used to test the hypothesis that the release of
      FFA in the brain is regulated by depolarization of neurons. This FFA release is
      likely the result of the activation of phospholipase A2. The increased neuronal
      activity that occurs due to synchronous depolarization during seizures causes
      activation of phospholipase A2. Decreasing neuronal activity by administering the
      anxiolytic, diazepam, appears to decrease the activity of phospholipase A2. The
      GABA antagonist, bicuculline, which causes depolarization by negating the
      hyperpolarizing tone imposed on neurons by GABA, causes FFA release in
      synaptosomes and in neurons in tissue culture. Likewise, the glutamate agonist,
      kainic acid, which depolarizes neurons by opening sodium channels, increases the
      activity of phospholipase A2. PC-specific phospholipase C, another enzyme
      important in the generation of the second messenger, DG, is also activated by
      depolarization. Several important questions remain to be answered. The site of
      FFA release, in terms of the pre-vs. postsynaptic membrane, is not clear,
      although the experiments with synaptosomes support the hypothesis that activation
      of phospholipase A2 may be an important regulator of presynaptic events. This
      idea has also been suggested by studies on the phenomenon of long-term
      potentiation, where free 20:4 or its metabolites may be involved in presynaptic
      facilitation of neurotransmitter release (Freeman et al., 1990; Massicotte et
      al., 1990; Williams et al., 1989; also see Dorman, this volume). The activation
      of the PI cycle and subsequent stimulation of protein kinase C may be a
      postsynaptic event important in the integration of inputs at the dendrite and
      soma or a presynaptic event involved in the modulation of neurotransmitter
      release (Taniyama et al., 1990; El-Fakahany et al., 1990; also see Nishizuka,
      this volume). Therefore the stimulation of a PC-specific phospholipase C, which
      is capable of generating large amounts of DG over a prolonged period of time
      (Exton, 1990; Martinson et al., 1990; Diaz-Laviada et al., 1990), could occur at
      either site. Another important question is the role of FFA and DG in affecting
      cell-cell signaling events, particularly with regard to ion fluxes. Modulation of
      an acetylcholine-linked K+ channel in the heart by FFA and their oxygenation
      products has been reported (Kim and Clapham, 1989). The cardiac muscarinic
      receptor is linked to a hyperpolarizing K+ channel via a G protein.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1353288
TI  - [Pulmonary embolism caused by liver tissue].
AB  - Embolism of hepatic tissue to the lung in coincidence with severe injury to the
      liver is a rare complication. We report on a case of a 22-year old motor-cyclist
      who was involved in a traffic accident and incured a blunt abdominal trauma. The
      autopsy revealed a crushed right hepatic lobe. Careful microscopically
      investigations of the lungs showed multiple small emboli composed primarily of
      hepatic tissue in pulmonary arterial branches.

PMID- 1353289
TI  - [Fat embolism and fracture, a review of the literature].
AB  - The reasons of fat embolism as well as the following fat embolism syndrome are
      most likely long bone fractures, especially if the femur is participated. On the
      other hand there are cases, where a severe concussion of the entire body caused
      fat embolism. But it is also supposed, that intramedullary reaming as well as the
      insertion of knee- and hip-prostheses could be a releasing factor, because the
      applicated pressure on the medullary canal can cause a fat release in the
      systemic blood system. The morbidity depends on age and fracture, which is on
      fractures between 0.9 and 2%. The most affected group are people between 18 and
      28 years of age. The fat embolism is manifesting at 46-60% of the patients in the
      first 24 hours and over 90% of the patients are affected in the first three days.
      If you look at the metabolic changes, you will find shortly after the fracturing
      process a rapid increase of free fatty acids (FFA), as well as an increase of the
      plasmatic enzyme levels (lipase, GPT, GOT, GLDH, LDH, etc.), catecholamines and
      glucocorticoids. In order to discuss the pathogenesis in a fairly complete way,
      you have to take different theories into consideration, because several parallel
      running processes--which are influencing each other--are leading to the syndrome.
      Infloating theory: Proceeding on the assumption that contents of the bone marrow
      are floating out of the fracture gap into the venous system and are leading to
      fat embolism in the lungs. Lipase theory: You can diagnose in 50-70% of the
      fracture patients an increase of the lipase level, which is correlating with the
      manifestation of the fat embolism. The lipase releases fat from the body
      depositories in addition to the fat, who is coming out of the fracture gap. Shock
      and coagulation theory: During shock the microcirculation is decelerated, the
      blood viscosity is increased and the suspension stability of the cellular blood
      components is decreased, which is leading to the sludging phenomenon. So the
      capillaries of the lungs and the brain are a kind of sludge filter of the blood,
      that is changed in its suspensions stability. Free fatty acids theory: Primary
      existing capillary defects are reasonable caused by free fatty acids (FFA). They
      are hydrolyzed of the neutral fats and are histotoxic for the walls of the blood
      vessels.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1353290
TI  - [Thromboembolism complications in orthopedics and traumatology. A prospective
      study of 598 operated patients].
AB  - From 1.10.-31.12. 1989, 598 patients who underwent orthopaedic surgery in the
      Staatliche Orthopadische Klinik were examined by a pre-, intra- and postoperative
      questionnaire up to 3 months from the date of operation. All patients were
      separated into 4 groups corresponding to the calculated risk and duration of the
      operation. 46 patients in Group I, who underwent minor surgery, received 3 x 5000
      I.E. Heparin subcutaneously. 243 patients in Group II received besides 3 x 5000
      I.E. Heparin, 500 ml HAES 6% preoperatively. They underwent operations of greater
      intensity and duration at the upper and lower extremities. 302 patients of Group
      III were given 3 x 5000 I.E. heparin and 500 ml 6% dextrane 60 preoperatively
      because of severe operations (pelvis, hip). 7 high-risk patients received apart
      from 3 x 5000 I.E. Heparin subcutaneously 500 ml 6% dextrane 60 preoperatively
      and 250ml 10% dextrane 40 postoperatively for 5 days. In Group I we had 2.2%
      thromboembolic complications, whereas in Group II 1.7% and in Group III 3.3%
      complications with thrombosis and pulmonary embolism occurred. This was proved by
      pulmonary scintigraphy and phlebography. No such complications were seen in Group
      IV. The total incidence of deep vein thrombosis was 2.0% and of pulmonary
      embolism 0.5%. These results show the importance of preoperative risk check and
      individual prophylaxis of thromboembolic complications in orthopaedic and
      traumatologic surgery.

PMID- 1353291
TI  - [Importance of the Segond avulsion fracture as a sign of complex ligamentous knee
      injury].
AB  - The Segond fracture is a small bony avulsion of the lateral tibial condyle. A
      study of 11 patients, treated between 1986 and 1990, points out the importance of
      this injury. In our series all patients showed an additional major ligamentous
      damage. 10 patients had an injury of the anterior cruciate ligament. This
      harmless "lateral capsular sign" on the standard x-ray of the knee-joint should
      give reason for further diagnostic measures, mainly the arthroscopic examination.

PMID- 1353292
TI  - [Importance of measuring stability and function in knee ligament surgery].
AB  - To compare results in knee ligament surgery between different surgeons and
      between different centers, too, is difficult. We investigated if an improvement
      can be achieved by using easy to handle methods of measurement. The long-term
      results of 180 patients who underwent ACL surgery between 1983 and 1986 (n = 191)
      were evaluated. For international comparing of our results we used the scoring of
      the OAK (Orthopadische Arbeitsgemeinschaft Knie). In addition stability was
      measured by use of the KT-1000 arthrometer and function by "one leg hop for
      distance". Together with different usual functional tests those two methods were
      investigated for being comparable, practicable, and relevant. We found that both
      measurements came up to these conditions. We succeeded in rating the patients'
      result by measuring KT-1000 and one leg hop for distance. Examination after knee
      ligament surgery has to contain these two parameters for international
      comparison.

PMID- 1353293
TI  - [Expert assessment of so-called post-thrombotic syndrome in compulsory accident
      insurance].
AB  - Expertising a late damage after thrombosis requires most careful investigation of
      the findings, a detailed description of the damage, and a definition of the
      impairment of functions. This is imperative for arriving at an administrative
      decision to implement the conclusions arrived at by the expert without committing
      a legal error by such implementation. Estimation and determination of the damage
      and of awarding a reasonable compensation requires a detailed consideration of
      the circumstances of each case and observance of the legal principle of equal
      rights.

PMID- 1353294
TI  - [A simple method for repositioning metatarsal fractures].
AB  - Because of small direct contact to the fracture fragments reduction of metatarsal
      fractures can be achieved only indirectly by applying traction to the toes. In
      this article a method for simple direct manipulation of the distal main fragment
      of metatarsal fractures is described: A K-wire is drilled in dorsi plantar
      direction across the head of the fractured metatarsal and mounted on a traction
      bow. In this manner the distal fracture fragment can be moved in all directions
      and placed exactly onto the proximal fragment. All 8 patients with multiple
      metatarsal fractures could be treated by closed reduction and percutaneous
      pinning. The described method allows simple and precise reduction of metatarsal
      fractures, reduced x-ray exposure of the surgeon's hand by short operation times,
      and manipulation for fracture reduction outside the x-ray beam.

PMID- 1353295
TI  - [Accidents with bicycles and motorcycles. The injury pattern, costs, and
      possibilities for prevention].
AB  - This review comprises all 641 patients subjected to inpatient treatment in 1976,
      1980 and 1984 at the Basel district hospital after accidents involving bicycles
      or motorcycles. A study of the case histories--supplemented by phone
      conversations--yielded the following results: Accidents involving bicycles or
      motor-driven bicycles were seen in all age groups, but motorcycle accidents
      occurred exclusively among the younger generation. Whereas motorcycle accidents
      mostly happened during joyrides, accidents with bicycles or mobikes mainly
      occurred on the way to work. The incidence rate was highest during summertime and
      in the rush hours at noon or in the evening. Motorcycle accidents resulted in
      more severe injuries, longer hospitalisation, longer periods of disability and
      higher costs than bicycle or mobike accidents the latter being mainly
      characterised by mostly slight head injuries and the former by injuries of the
      legs and arms.

PMID- 1353296
TI  - [Gunshot injuries--their incidence and surgical problems].
AB  - Since the time when firearms became readily available, surgeons have had to deal
      with the gunshot wounds which have presented for treatment. In middle europe, in
      peace time, gunshot wounds account for only a small percentage of the total
      number of trauma cases seen. This is reflected in our patient census in which a
      mere 0.065% of cases were associated with such injuries. It would seem that a
      relevant knowledge of the technical and physical attributes of firearms is
      important. With this understanding, the formulation of an according treatment
      plan is made easier. Gunshot wounds are frequently not confined to the
      extremities. The trauma surgeon, who largely deals with limb injuries, is now
      confronted with an increasing number of chest and trunk wounds and their
      particular therapeutic consequences.

PMID- 1353297
TI  - Selective dopamine-1 receptor agonist augments regional myocardial blood flow:
      comparison of fenoldopam and dopamine.
AB  - A new class of vasodilators exhibiting selective dopamine-1 receptor agonist
      activity is being introduced into clinical practice. Inasmuch as various
      vasodilators either augment or decrease myocardial blood flow ("coronary steal")
      depending on their pharmacologic action, the goal of this study was to assess the
      effects of fenoldopam (selective dopamine-1 receptor agonist) and dopamine
      (nonselective dopamine-1 receptor agonist) on regional myocardial blood flow in
      the presence of coronary occlusion. Accordingly, in 16 dogs anesthetized with
      pentobarbital, the left anterior descending coronary artery was occluded.
      Cardiovascular and renal hemodynamic effects were measured before and after
      intravenous infusion of renal equipotent doses of either fenoldopam (n = 9, 0.1
      micrograms/kg/min) or dopamine (n = 7, 1 micrograms/kg/min). Both fenoldopam and
      dopamine caused a significant and comparable increase in renal blood flow.
      Fenoldopam but not dopamine significantly decreased the calculated peripheral
      vascular resistance and subsequently increased cardiac output. Dopamine had no
      effect on regional myocardial blood flow. In contrast, fenoldopam augmented
      transmural myocardial blood flow in normal (from 114 +/- 10 to 188 +/- 27 ml/100
      gm/min, p less than 0.02) and ischemic border myocardium (from 45 +/- 5 to 68 +/-
      11 ml/100 gm/min, p less than 0.03 and p less than 0.02 vs dopamine). There was a
      significant increase in blood flow to both the endocardial and epicardial layers
      of normal and ischemic border myocardium. These changes were accompanied by a
      significant reduction in coronary vascular resistance in the normal
      myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353298
TI  - Biochemical mechanisms involved in the beta-blocker-induced changes in serum
      lipoproteins.

PMID- 1353300
TI  - Pathological case of the month. Medullary thyroid carcinoma in multiple endocrine
      neoplasia type IIB.

PMID- 1353299
TI  - CD4 status and P24 antigenemia. Are they useful predictors of survival in HIV
      infected children receiving antiretroviral therapy?
AB  - OBJECTIVE: To determine the relationship between CD4 status and the P24 antigen
      level and survival in children infected with the human immunodeficiency virus.
      DESIGN: Cohort, case-control. SETTING: Clinical Center at the National Institutes
      of Health, Bethesda, Md. PARTICIPANTS: One hundred forty-seven children infected
      with the human immunodeficiency virus enrolled in antiretroviral therapy
      protocols at the National Cancer Institute were reviewed and the relationships
      between CD4 counts, P24 antigenemia, and death were analyzed. INTERVENTIONS:
      None. MEASUREMENTS/MAIN RESULTS: The presence of a very low CD count, less than
      21% of the lower limit of normal values for age (equivalent to 0.05 x 10(9)/L in
      an adult), was associated with a significantly increased risk of death within 2
      years. Although the risk of death was highest for children with CD4 counts below
      this level and who had detectable P24 antigen levels, P24 antigenemia by itself
      contributed little to the prognostic value of the CD4 count alone. However, it
      was also notable that a group of children with low CD4 counts also experienced
      prolonged survival. CONCLUSIONS: The association between low CD4 counts and death
      suggests that the age-adjusted CD4 count should be used as a marker to guide
      therapeutic intervention. At the same time, the presence of a very low CD4 count
      alone should not be considered a reason for therapeutic nihilism.

PMID- 1353301
TI  - Adrenergic and nonadrenergic cotransmitters inhibit insulin secretion during
      sympathetic stimulation in dogs.
AB  - Vascular and biochemical responses to pancreatic sympathetic nerve stimulation
      were investigated in the blood-perfused pancreas of anesthetized dogs. During
      sympathetic nerve stimulation, pancreatic perfusion pressure and norepinephrine
      release increased, whereas insulin secretion decreased. The latter effect did not
      occur after pretreatment with the alpha 2-adrenoceptor antagonist idazoxan.
      However, after beta-adrenoceptor blockade with propranolol, neither single
      administration of idazoxan nor the alpha 1-adrenoceptor antagonist prazosin or
      glibenclamide, a blocker of ATP-modulated K+ channels, affected the decrease in
      insulin secretion induced by sympathetic nerve stimulation. In contrast, the
      combination of glibenclamide with idazoxan markedly antagonised the decrease in
      insulin release evoked by the latter procedure. After depletion of catecholamines
      with syrosingopine, the stimulation-induced inhibition of insulin secretion
      remained unchanged even though no increases in pancreas perfusion pressure or
      norepinephrine release were observed. In this preparation, glibenclamide
      inhibited the decrease in insulin release by 50%. In animals pretreated with the
      neuronal blocking agent bretylium, all of the responses to sympathetic nerve
      stimulation were abolished. These results indicate that the inhibitory effects
      exerted by the sympathetic nervous system on insulin secretion are mediated not
      only by the classical neurotransmitter norepinephrine acting on alpha 2
      adrenoceptors but also by a nonadrenergic cotransmitter that can maintain
      transmission under conditions of catecholamine deficiency. The postulated
      nonadrenergic cotransmitter(s) acts, at least partly, via the opening of ATP
      modulated K+ channels blockable by glibenclamide, and its release can be
      prevented by the neuronal blocking agent bretylium.

PMID- 1353302
TI  - Effects of erythromycin in the dog upper gastrointestinal tract.
AB  - The effects of erythromycin on motor and electrical behavior of the antrum,
      pylorus, and duodenum were determined in chronically instrumented, awake dogs.
      Erythromycin infusion resulted in an abrupt, powerful increase in motility. The
      motility index increased 18-fold in the antrum, 15-fold in the pylorus, and 8
      fold in the duodenum. Bradyarrhythmia with a 30% decrease in slow-wave frequency
      occurred in all animals. Retrograde giant contractions in association with
      retching and vomiting occurred in 88% of the dogs. Neostigmine was less potent
      than erythromycin in increasing motility. Hexamethonium given intra-arterially
      during erythromycin infusion abolished motility for 7.2 +/- 2.9 min and intra
      arterial atropine did so for 51 +/- 25 min. Hexamethonium or atropine restored
      the electrical slow-wave frequency. The results provide evidence that
      erythromycin action involves cholinergic pathways including ganglionic
      transmission.

PMID- 1353303
TI  - Guanylate cyclase inhibitors: effect on inhibitory junction potentials in
      esophageal smooth muscle.
AB  - Electrical field stimulation (EFS) of nerves intrinsic to the opossum lower
      esophageal sphincter (LES) produces LES relaxation, an increase in its guanosine
      3',5'-cyclic monophosphate (cGMP) content, and hyperpolarization of its circular
      muscle membrane potential difference. Activation of esophageal nerves produces an
      analogous hyperpolarization of the circular esophageal smooth muscle. These
      studies test the hypothesis that cGMP is an intracellular mediator of this
      hyperpolarization. The transmembrane potential difference of circular smooth
      muscle cells was recorded with glass microelectrodes. Nerve-mediated smooth
      muscle hyperpolarization was evoked by EFS (1 ms, 50 V pulses). Forskolin, an
      activator of adenylate cyclase, and sodium nitroprusside, an activator of
      guanylate cyclase, produced hyperpolarization. Cystamine and methylene blue,
      inhibitors of guanylate cyclase, blocked the hyperpolarization elicited by sodium
      nitroprusside, but not that by forskolin. Both also reversibly abolished the
      hyperpolarization evoked by EFS. Membrane-permeable derivatives of cGMP produced
      a concentration-dependent hyperpolarization. These data support the hypothesis
      that cGMP is an intracellular mediator of nerve-induced esophageal smooth muscle
      hyperpolarization.

PMID- 1353304
TI  - Guanylate cyclase inhibitors: effect on tone, relaxation, and cGMP content of
      lower esophageal sphincter.
AB  - Relaxation of the lower esophageal sphincter (LES) results from activation of its
      intrinsic innervation. This relaxation is associated temporally with an increase
      in the guanosine 3',5'-cyclic monophosphate (cGMP) content of the muscle. This
      study tests the hypothesis that variations in the production of cGMP mediate
      resting LES tone and nerve-induced relaxation. We examined the effects of
      guanylate cyclase inhibitors, such as cystamine and methylene blue (MB), on the
      resting tone, resting membrane potential, electrical field stimulation (EFS)
      induced relaxation, and cGMP content of circular smooth muscle from the LES of
      the opossum. Strips of sphincter muscle were placed in a tissue bath and
      stretched to 125% resting length. Both cystamine and MB increased the resting
      tone of LES muscle in a concentration-dependent manner (EC50 = 1.1 +/- 0.2, n =
      12, and 1.6 +/- 0.4 mM, n = 10, respectively). The increase in tone by cystamine
      was not blocked by tetrodotoxin, atropine, or propranolol. Cystamine (1 mM) did
      not alter the resting membrane potential of circular muscle cells of the LES. The
      removal of extracellular Ca2+ by the addition of ethylene glycol-bis(beta
      aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA, 4 mM) and nifedipine (1
      microM) shortened the duration but not the amplitude of the response to
      cystamine. Pretreatment with caffeine (5 mM) in the presence of EGTA and
      nifedipine to deplete intracellular Ca2+ stores blocked the increase in tone by
      cystamine. Cystamine (1 mM) failed to inhibit LES relaxation induced by EFS.
      Carbachol, at a concentration that induced a similar increase in base-line tone,
      attenuated the nerve-mediated relaxation. Cystamine did not alter basal cGMP
      levels, but inhibited the rise in cGMP induced by EFS. The data indicate that
      cystamine increases LES tone but does not inhibit EFS-induced relaxation, even
      though it inhibits EFS-induced increases in cGMP content. The increase in tone is
      dependent on the presence of intracellular Ca2+ stores.

PMID- 1353305
TI  - Pulmonary arterial hypoxic contraction: signal transduction.
AB  - The response of isolated rat pulmonary arteries to acute hypoxia has previously
      been reported to be biphasic, consisting of an initial rapid contraction of short
      duration, followed by partial relaxation (phase 1) and then a second slowly
      developed but sustained contraction (phase 2). The purpose of this study was to
      determine the following: 1) whether products from the endothelium might be
      required, 2) whether extra- and/or intracellular calcium or protein kinase C
      might be second messengers in mediating the pulmonary arterial hypoxic
      contraction, and 3) whether or not guanosine 3',5'-cyclic monophosphate (cGMP),
      endothelium-derived relaxing factor (EDRF), prostaglandin I2 (PGI2) or A2
      adenosine receptor activation is involved in phase 1 relaxation. Neither Ca(2+)
      free media nor verapamil (a Ca2+ channel blocker) altered the phase 1
      contraction, but the phase 2 contraction was abolished by either of these
      treatments. Ryanodine (a sarcoplasmic reticulum Ca2+ depleter) had no effect on
      phase 1 contraction. H-7 (a PKC inhibitor) inhibited the phase 2 contraction,
      whereas it had no effect on phase 1 contraction. Removal of the endothelium
      abolished phase 1 contraction in either Ca(2+)-free media or normal Ca2+ media
      but did not alter phase 2 contraction or phase 1 relaxation. Neither methylene
      blue (guanylate cyclase inhibitor), N omega-nitro-L-arginine, (EDRF blocker),
      acetylsalicylic acid (cyclooxygenase inhibitor), xanthine amino congener
      (adenosine receptor blocker), nor glybenclamide blocked the phase 1
      relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353306
TI  - Selective induction of intercellular adhesion molecule-1 by interferon-gamma in
      human airway epithelial cells.
AB  - To evaluate the factors controlling migration of leukocytes into pulmonary airway
      epithelium, we determined the biochemical mechanisms responsible for the
      regulation of intercellular adhesion molecule-1 (ICAM-1) expression on cultured
      monolayers of human tracheal epithelial cells (HTECs) or SV40 virus-transformed
      human bronchial epithelial cells (BEAS-2B). Validation experiments with human
      umbilical vein endothelial cells (HUVECs) demonstrated little detectable ICAM-1
      expression on unstimulated cells or on cells incubated with interferon-gamma (IFN
      gamma), but HUVEC monolayers responded to interleukin-1 beta (IL-1 beta) or tumor
      necrosis factor-alpha (TNF-alpha) with significant increases in ICAM-1 and ICAM-1
      dependent adherence of polymorphonuclear leukocytes (PMNs). HTEC monolayers also
      exhibited no significant basal ICAM-1 expression but, in contrast to HUVEC
      monolayers, had marked increases in ICAM-1 expression and ICAM-1-dependent PMN
      adherence only after incubation with IFN-gamma (and not after IL-1 beta or TNF
      alpha) treatment. BEAS-2B cells also exhibited relatively selective IFN-gamma
      stimulation of ICAM-1 expression and ICAM-1-dependent PMN adherence but (like
      late passage HTEC) showed significant basal ICAM-1 expression. Differences in IFN
      gamma effect on ICAM-1 levels between HUVEC and HTEC monolayers were not due to
      differences in number or responsiveness of IFN-gamma receptors, because both cell
      types exhibited a similar number of receptors and other IFN-gamma-dependent
      responses of HUVECs remained active. In all analyses, ICAM-1 mRNA levels
      correlated closely with detection of ICAM-1 on the cell surface.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1353307
TI  - Renal receptors for atrial and C-type natriuretic peptides in the rat.
AB  - Receptors for alpha-atrial natriuretic peptide (alpha-ANP) and C-type natriuretic
      peptide [CNP-(1-22)] were quantified in kidneys from adult Wistar rats by in
      vitro autoradiography. 125I-labeled alpha-ANP (100 pM) bound reversibly to
      glomeruli, outer medullary vasa recta, and inner medulla with an apparent
      dissociation constant (Kd) of 3-6 nM. The presence of 10 microM des
      [Gln18,Ser19,Gly20,Leu21,Gly22]ANP-(4- 23) (C-ANP), a specific ligand of the ANPR
      C subtype of alpha-ANP receptor, inhibited approximately 50% of the glomerular
      binding of 125I-alpha-ANP, and this moiety of glomerular binding was also
      inhibited by CNP-(1-22) with an apparent inhibitory constant (Ki) of 10.47 +/-
      7.59 nM. C-ANP and CNP-(1-22) showed little affinity for the medullary binding
      sites of alpha-ANP. 125I-[Tyr0]CNP-(1-22) (110 pM) bound solely to glomeruli and
      was competitively displaced by increasing concentrations of [Tyr0]CNP-(1-22) with
      an apparent Kd of 1.42 +/- 0.48 nM. Binding of increasing concentrations (25 pM
      to 1 nM) of 125I-[Tyr0]CNP-(1-22) in the presence or absence of 1 microM
      [Tyr0]CNP-(1-22) also demonstrated a high affinity (Kd of 0.41 +/- 0.07 nM) for
      the glomerular binding of 125I-[Tyr0]CNP-(1-22). Bound 125I-[Tyr0]CNP-(1-22)
      could be displaced by excess alpha-ANP and excess CNP-(1-22), both with high
      affinities. The glomerular binding of 125I-[Tyr0]CNP-(1-22) was also prevented by
      10 microM C-ANP. Guanosine 3',5'-cyclic monophosphate produced by isolated
      glomeruli was measured by radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353309
TI  - Lower brain stem controls cardiac ANF secretion.
AB  - The purpose of these studies was to investigate whether the central nervous
      system (CNS) can modulate the plasma level of atrial natriuretic factor (ANF). In
      anesthetized, spontaneously breathing rats, electrical stimulation was
      stereotaxically applied bilaterally to four medullary nuclei: 1) the rostral
      nucleus of the solitary tract (rNTS), 2) the intermediate portion of the NTS
      (iNTS), 3) the ventrolateral nucleus ambiguus (NA) 0.3 mm rostral to obex, and 4)
      the rostral ventrolateral medulla (RVL). Electrical stimulation of the rNTS and
      RVL caused a 55 +/- 18% (P less than 0.025, n = 6) and 187 +/- 80% (P less than
      0.001, n = 5) increase in plasma ANF, respectively, compared with baseline (56-88
      pg/ml), whereas sham stimulations had no effect on plasma ANF release. In
      contrast, electrical stimulation of the iNTS and the NA elicited a 35 +/- 6 (P
      less than 0.01, n = 7) and 31 +/- 6% (P less than 0.05, n = 5) decrease in plasma
      ANF, respectively. In artificially ventilated rats, unilateral electrical
      stimulation of the RVL induced a 94 +/- 39 (left RVL, n = 6, P less than 0.01)
      and 186 +/- 68% (right RVL, P less than 0.01, n = 5) increase in plasma ANF over
      baseline. Unilateral microinjection of L-glutamate into RVL also resulted in a 81
      +/- 23% (n = 9, P less than 0.01) increase in plasma ANF compared with baseline
      and vehicle control injections. These results suggest that activation of the
      central sympathetic system potently stimulates the secretion of cardiac ANF.

PMID- 1353308
TI  - Dynorphin, naloxone, and overflow of norepinephrine during cardiac nerve
      stimulation in dogs.
AB  - The effects of dynorphin-(1-9) and naloxone on norepinephrine (NE) overflow and
      myocardial contractility were determined during left cardiac nerve stimulation in
      the anesthetized dog. Stimulation-induced increases in NE overflow from the left
      ventricle were monitored during control conditions, during infusion of dynorphin
      (1-9), during dynorphin plus naloxone, and after naloxone alone. Four electrical
      stimulations were applied for 1 min at 20-min intervals. Repeated left cardiac
      nerve stimulations (control group) reduced stimulated NE overflow 50-60% by 1 h.
      If stimulations were only conducted at 0 and 1 h, the decline in NE overflow was
      not observed. Intracoronary dynorphin (2 nmol.min-1.kg-1, 20 min) lowered the
      stimulation-induced increase in NE overflow further and reduced first time
      derivative of left ventricular pressure (dP/dt) and myocardial O2 consumption
      responses. Naloxone (100 micrograms/kg) prevented all of the dynorphin-mediated
      effects. When given alone, naloxone increased both NE overflow and left
      ventricular dP/dt during stimulation and prevented or significantly delayed the
      gradual decline in overflow observed in stimulated controls. A postjunctional
      effect of dynorphin was evaluated by comparing contractile responses to the
      intracoronary infusion of NE before and during dynorphin. Dynorphin did not alter
      contractile function at rest or during NE infusion. In summary, dynorphin-(1-9)
      depresses nerve stimulation-induced, cardiac NE overflow, and myocardial
      contractility in a naloxone-reversible fashion. Alone, naloxone appears to
      regulate stimulated NE overflow through a qualitatively different mechanism.
      Endogenous opioids may normally moderate myocardial function during cardiac nerve
      stimulation by regulating junctional NE concentrations through a combination of
      effects on NE release and/or its subsequent reuptake.

PMID- 1353310
TI  - Pituitary-adrenal responses to head-up tilt in humans: effect of H1- and H2
      receptor blockade.
AB  - Effects of the histamine H1- or H2-receptor antagonists mepyramine (Mep) and
      cimetidine (Cim) on neuroendocrine and cardiovascular responses to 50 degrees
      head-up tilt were evaluated in seven human males. Central hypovolemia was
      characterized by two phases. The first is a normotensive phase with increases in
      heart rate (HR), total peripheral resistance (TPR), and decrease in cardiac
      output. Plasma adrenocorticotropic hormone, beta-endorphin, cortisol,
      catecholamines, and renin activity increased moderately. Normotension lasted 39
      +/- 7 min during infusion of saline but was reduced by Mep [18 +/- 3 min, F(2,12)
      = 9.60, P less than 0.01] and was unaffected by Cim (44 +/- 4 min). The second is
      a hypotensive phase associated with presyncopal symptoms (hypovolemic shock) and
      decreases in HR and TPR and a further increase in pituitary-adrenal and
      sympathoadrenal activity. Decreases in mean arterial pressure and TPR were
      augmented by Mep, which inhibited release of norepinephrine. Cim inhibited
      epinephrine release without affecting the development of hypovolemic shock. It is
      concluded that histaminergic mechanisms are involved in activation of the
      sympathoadrenal system but not in the pituitary-adrenal axis during central
      hypovolemia in humans.

PMID- 1353311
TI  - Adrenergic regulation of neonatal brown fat adenylyl cyclase and Gs alpha
      activity.
AB  - Norepinephrine (NE)-stimulated adenylyl cyclase (AC) activity increases during
      the perinatal period in rat brown adipose tissue (BAT), and this increase is
      associated with changes in the activities of both the catalytic subunit (C) and
      Gs alpha, the GTP-binding protein that mediates activation of C. The present
      study examined the role of the sympathetic nervous system in the postnatal
      sensitization of AC. The sympathetic innervation of BAT increased 7- to 13-fold
      after birth, and this increase was temporally correlated with the postnatal
      enhancement of AC responsiveness. 6-hydroxydopamine (6-HDA) treatment of neonates
      reduced tyrosine hydroxylase levels by greater than 90%. This treatment greatly
      reduced the perinatal increase in NE- and NaF-stimulated AC and completely
      abolished the increase in forskolin-Mn(2+)-stimulated activity. However,
      sympathectomy did not alter the postnatal increase in Gs alpha-specific activity
      and did not prevent the postnatal reduction in Gs alpha levels. These results
      demonstrate that the sympathetic innervation of BAT develops fully after birth
      and is essential for the postnatal increase in the activity of C but not of Gs
      alpha.

PMID- 1353312
TI  - Possible mediation by luminal somatostatin of bombesin-induced satiety in the
      cat.
AB  - Intravenous bombesin produced a dose-related stimulation of luminal gastric
      somatostatin output and a concomitant dose-dependent inhibition of food intake in
      the gastric fistula cat. Maximal food intake inhibition was observed at 1,280
      pmol.kg-1.h-1 and corresponded to 65 +/- 7% (P less than 0.01). These effects of
      bombesin were dose dependently abolished by the specific bombesin-receptor
      antagonist, [Leu13-psi(CH2NH)-Leu14]bombesin. Furthermore, intragastric
      administration of somatostatin-14, at doses corresponding to those found in the
      gastric lumen in response to intravenously administered bombesin, significantly
      inhibited the first 30 min of food intake. This administration had however no
      effect on total (daily) food intake. We therefore suggest that luminal gastric
      somatostatin could at least account for bombesin-induced short-term satiety.

PMID- 1353313
TI  - Bright light treatment of behavioral and sleep disturbances in patients with
      Alzheimer's disease.
AB  - OBJECTIVE: The authors tested the hypothesis that evening bright light pulses
      would improve sleep-wake patterns and reduce agitation in patients with
      Alzheimer's disease who have severe sundowning (a syndrome of recurring confusion
      and increased agitation in the late afternoon or early evening) and sleep
      disorders. METHOD: Ten inpatients with Alzheimer's disease on a research ward of
      a veterans' hospital were studied in an open clinical trial. All patients had
      sundowning behavior and sleep disturbances. After a week of baseline
      measurements, patients received 2 hours/day of exposure to bright light between
      7:00 p.m. and 9:00 p.m. for 1 week. During the baseline week, the treatment week,
      and a posttreatment week, patients were rated by nurses for agitation, sleep-wake
      patterns, use of restraints, and use of prescribed-as-needed medication. On the
      last 2 days of each week, patients wore activity monitors. Activity counts were
      analyzed for circadian rhythmicity. RESULTS: Clinical ratings of sleep
      wakefulness on the evening nursing shift improved with light treatment in eight
      of the 10 patients. The proportion of total daily activity occurring during the
      nighttime decreased during the light-treatment week. The relative amplitude of
      the circadian locomotor activity rhythm, a measure of its stability, increased
      during the light-treatment week. More severe sundowning at baseline predicted
      greater clinical improvement. CONCLUSIONS: Evening bright light pulses may
      ameliorate sleep-wake cycle disturbances in some patients with Alzheimer's
      disease. This effect may be mediated through a chronobiological mechanism.

PMID- 1353314
TI  - Toward a brain map of auditory hallucinations.
AB  - OBJECTIVE: This study asks whether auditory hallucinations are reflected in a
      distinctive metabolic map of the brain. METHOD: Regional brain metabolism was
      measured by positron emission tomography with [18F]-fluorodeoxyglucose in 12 DSM
      III schizophrenic patients who experienced auditory hallucinations during glucose
      uptake and 10 who did not. All patients were free of neuroleptics and 19 had
      never been treated with neuroleptics. Nine patients were reexamined after 1 year
      to assess effects of neuroleptic treatment. RESULTS: Compared with the patients
      who did not experience hallucinations, the patients who did experience
      hallucinations had significantly lower relative metabolism in auditory and
      Wernicke's regions and a trend toward higher metabolism in the right hemisphere
      homologue of Broca's region. Hallucination scores correlated positively and
      significantly with relative metabolism in the striatum and anterior cingulate
      regions. Neuroleptic treatment resulted in a significant increase in striatal
      metabolism and a reduced frontal-parietal ratio, which was significantly
      correlated with a decrease in hallucination scores. CONCLUSIONS: Auditory
      hallucinations involve language regions of the cortex in a pattern similar to
      that seen in normal subjects listening to their own voices but different in that
      left prefrontal regions are not activated. The striatum plays a critical role in
      auditory hallucinations.

PMID- 1353315
TI  - Painful sensory symptoms in neuroleptic-induced extrapyramidal syndromes.
AB  - OBJECTIVE: The authors tested the hypothesis that neuroleptic-induced
      extrapyramidal syndromes are associated with painful sensations objectively
      conforming to the characteristics of primary sensory symptoms as reported in
      idiopathic and postencephalitic parkinsonism. METHOD: The frequency of subjective
      painful sensory symptoms and their relation to neuroleptic-induced extrapyramidal
      syndromes were examined in a consecutive series of 107 psychiatric patients newly
      admitted to acute care units at a teaching hospital. Patients without illnesses
      or conditions likely to be associated with pain were included in the study if
      they had a diagnosis other than organic mental syndromes and were receiving
      psychotropic medications as prescribed by their treating physicians. Structured
      interviews with a modified version of the McGill Pain Questionnaire to assess
      sensory complaints and neurological examinations for neuroleptic-induced
      extrapyramidal syndromes (parkinsonism and akathisia) were conducted
      independently by two raters blind to each other's findings and patients'
      medication status. RESULTS: Fourteen (23%) of 60 patients receiving neuroleptics
      reported experiences of spontaneous pain subjectively attributed to
      pharmacological treatment, compared with only one (2%) of 47 patients receiving
      psychotropic medications other than neuroleptics. There was no difference between
      these two groups in subjective complaints of paresthesia (8% versus 9%). Twelve
      (55%) of the 22 patients with neuroleptic-induced extrapyramidal syndromes
      reported pain, compared with only two (5%) of the 38 patients who received
      neuroleptics but did not experience extrapyramidal syndromes. CONCLUSIONS:
      Although consonant with the study hypothesis, these results should be regarded as
      preliminary and interpreted conservatively in the light of the methodological
      limitations of the study.

PMID- 1353316
TI  - Prevalence of tardive dyskinesia, tardive dystonia, and respiratory dyskinesia
      among Chinese psychiatric patients in Hong Kong.
AB  - OBJECTIVE: Only scanty information on the prevalence of tardive dyskinesia in
      Chinese patients has been available. This study was undertaken to examine the
      prevalence of tardive dyskinesia, tardive dystonia, and respiratory dyskinesia in
      Chinese psychiatric patients in Hong Kong. METHOD: All inpatients of a mental
      hospital in Hong Kong, except those in the admission and children's wards, were
      surveyed with the Abnormal Involuntary Movement Scale, and standard research
      criteria were used to establish the diagnosis of tardive dyskinesia. In addition,
      patients were screened for tardive dystonia, according to published criteria, and
      for respiratory dyskinesia by physical examination and laboratory tests. RESULTS:
      Among the 917 patients surveyed, the prevalence rates were 9.3% for tardive
      dyskinesia, 0.4% for tardive dystonia, and 1.2% for respiratory dyskinesia. With
      multivariate analysis, greater age and a lower current dose of antipsychotic, but
      not the presence of mood disorder, were factors found to be significantly
      associated with tardive dyskinesia. CONCLUSIONS: The prevalence rates were much
      lower than those found in Western studies. This may indicate that there is an
      ethnic difference in the prevalence of these conditions. Prospective cross
      cultural studies are necessary to explore this possibility.

PMID- 1353317
TI  - CSF beta-endorphin and dynorphin in bulimia nervosa.
AB  - OBJECTIVE: Preclinical and clinical evidence suggests that central opioid
      dysfunction may play a role in the pathophysiology of the eating disorders. In
      particular, endogenous opioids are known to regulate feeding behavior, mood,
      perception, and neuroendocrine function, all of which are disturbed in patients
      with eating disorders. Although low concentrations of CSF beta-endorphin have
      been reported in low-weight patients with anorexia nervosa, central opioid
      activity in normal-weight patients with bulimia nervosa has not been reported.
      The authors therefore measured CSF concentrations of beta-endorphin and dynorphin
      in drug-free female patients with DSM-III-R-defined bulimia nervosa and normal
      comparison subjects. METHOD: After 4 days of a low monoamine diet and overnight
      bed rest, CSF was obtained (12-26 cc) from 11 women with bulimia and 17 normal
      comparison subjects (eight women and nine men). RESULTS: The women with bulimia
      had significantly lower CSF concentrations of beta-endorphin than did the female
      comparison subjects. However, CSF concentrations of dynorphin were not
      significantly different in patients and female or male comparison subjects. beta
      Endorphin concentrations were inversely correlated with Beck Depression Inventory
      scores and the depression subscale of the Eating Disorders Inventory.
      CONCLUSIONS: These data support a role for central opiates in the mediation of
      the pathophysiology of the signs and symptoms of bulimia nervosa, although it is
      impossible to rule out the effects of depression on the results.

PMID- 1353318
TI  - Rare presentation of tardive dyskinesia.

PMID- 1353319
TI  - Prevalence of abnormal movement disorders associated with neuroleptics.

PMID- 1353320
TI  - Involuntary facial movements, not all medication-induced.

PMID- 1353321
TI  - Psychodynamic psychiatry in the "decade of the brain".
AB  - OBJECTIVE AND METHOD: To illustrate the continued relevance of psychodynamic
      thinking in the practice of contemporary psychiatry, the author reviews a number
      of studies that demonstrate the intimate connection between psychosocial and
      neurophysiological factors in the etiology and pathogenesis of psychiatric
      disorders. A survey of three specific anxiety disorders illustrates the complex
      interaction between mind and brain in these disorders. RESULTS: Research on both
      primates and humans suggests that psychological influences result in permanent
      alterations of a neurobiological nature. Similarly, psychological interventions
      in a treatment context may have a profound impact on neurophysiology. Clinical
      case examples demonstrate that "biologically based" disorders may be rich in
      unconscious meaning. Clinical understanding of the meaning of symptoms may be
      instrumental in ensuring patients' compliance with pharmacotherapy regimens and
      in the removal of other resistances to treatment. CONCLUSIONS: In contemporary
      psychiatry, a psychodynamic perspective must be preserved. Without it, meaning
      will be lost, and both diagnostic understanding and informed treatment planning
      will suffer as a result.

PMID- 1353322
TI  - Transduction of psychosocial stress into the neurobiology of recurrent affective
      disorder.
AB  - Early clinical observations and recent systematic studies overwhelmingly document
      a greater role for psychosocial stressors in association with the first episode
      of major affective disorder than with subsequent episodes. The author postulates
      that both sensitization to stressors and episode sensitization occur and become
      encoded at the level of gene expression. In particular, stressors and the
      biochemical concomitants of the episodes themselves can induce the protooncogene
      c-fos and related transcription factors, which then affect the expression of
      transmitters, receptors, and neuropeptides that alter responsivity in a long
      lasting fashion. Thus, both stressors and episodes may leave residual traces and
      vulnerabilities to further occurrences of affective illness. These data and
      concepts suggest that the biochemical and anatomical substrates underlying the
      affective disorders evolve over time as a function of recurrences, as does
      pharmacological responsivity. This formulation highlights the critical importance
      of early intervention in the illness in order to prevent malignant transformation
      to rapid cycling, spontaneous episodes, and refractoriness to drug treatment.

PMID- 1353323
TI  - Pancreaticoduodenectomy.
AB  - Few major abdominal operations have undergone the extent of dramatic change as
      that associated with pancreaticoduodenectomy in the last 20 years. The
      precipitous drop in the mortality rate most likely has a multifaceted
      explanation. Possibilities include the concentration of the operations at
      specialized centers, the improvement in the quality of critical care and
      anesthesia, and the improvement in the skill and experience of surgeons
      performing the procedure. Concomitant with the drop in the morality rate has been
      an increase in the resectability rate, along with the early encouraging evidence
      of improved long-term survival. However, many aspects of the technical portion of
      the procedure, particularly the pancreaticojejunostomy, need to be evaluated in
      prospective trials. The changes in the mortality and resectability rates make the
      operation more widely available to a larger number of patients, and the
      effectiveness of pancreaticoduodenectomy even for palliation is now well
      established.

PMID- 1353325
TI  - [XVIII Spanish Congress of Pediatrics and I Extraordinary Congress of the ALAPE.
      Seville, 9-13 June 1992].

PMID- 1353326
TI  - Neurotoxins and Neurodegenerative Disease. New York Academy of Sciences
      conference. New York, New York, May 6-8, 1991.

PMID- 1353324
TI  - [The SPECT demonstration of an improvement in cerebral perfusion in a female
      patient with Takayasu's disease following carotid revascularization].
AB  - Computed tomography and magnetic resonance imaging play an important role in the
      diagnosis of cerebrovascular disease, but only in the morphological aspect. To
      assess changes in cerebral perfusion are necessary functional images techniques
      such as positron emission tomography (PET) and single-photon emission computed
      tomography (SPECT). By these methods we can evaluate the cerebral hemodynamics to
      better understand the significance of chronic ischemia as a stroke risk factor
      for patients with carotid stenosis. A case of improvement of cerebral blood flow
      demonstrated by SPECT after carotid revascularization in a young woman with
      Takayasu's disease is described.

PMID- 1353327
TI  - Excitotoxins: possible mechanisms of action.

PMID- 1353329
TI  - Modulatory action of kainic acid on glutamate release from rat brain cortical
      synaptosomes.

PMID- 1353328
TI  - Neurotoxin-related research: from the laboratory to the clinic.

PMID- 1353330
TI  - The potential neurotoxin 2-OH-dopamine is an inhibitor of arylsulfatase.

PMID- 1353331
TI  - Neurotoxicity of an MPTP analogue, 2'CH3-MPTP, on monoaminergic systems in the
      mouse brain.

PMID- 1353332
TI  - The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) alters
      immune function when given in combination with diethyldithiocarbamate (DDC).

PMID- 1353333
TI  - Subcellular compartmentation of 2'methyl MPP+ can explain differences in toxicity
      to adrenal chromaffin cells.

PMID- 1353334
TI  - Excitatory amino acid-evoked calcium influx and calcium-dependent neurotoxicity
      in rat cortical cultures.

PMID- 1353335
TI  - Comparison of the release of exogenous and endogenous excitatory amino acids from
      rat cerebral cortex.

PMID- 1353336
TI  - NMDA receptors, cellular edema, and metabolic stress.

PMID- 1353337
TI  - Midbrain dopaminergic cell loss in Parkinson's disease and MPTP-induced
      parkinsonism: sparing of calbindin-D28k-containing cells.
AB  - Computer imaging and immunohistochemical staining techniques were used to
      determine which midbrain dopaminergic (DA) cells are spared in Parkinson's
      disease (PD), and in animals treated with the DA neurotoxin 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP), and whether the spared cells contain the
      calcium-binding protein, calbindin-D28k (CaBP). The PD patients had more than 55%
      fewer midbrain DA neurons than age-matched normal subjects. The cell loss
      occurred within the combined substantia nigra and retrorubral area (greater than
      61%; DA nuclei A9 and A8, respectively), and the ventral tegmental area (greater
      than 42%; DA nucleus A10). The cell loss was greatest within the ventral portion
      of the nucleus A9. A similar pattern of DA cell loss was observed in MPTP-treated
      Macaca fascicularis monkeys. The CaBP-containing cells were located specifically
      in the cell regions spared by PD and by MPTP-treatment in both monkeys and
      C57BL/6 mice. These data suggest that PD and MPTP both destroy the same
      population of midbrain DA neurons within nuclei A8, A9, and A10, and that perhaps
      CaBP protects the DA neurons from cell death caused by both PD and MPTP.

PMID- 1353338
TI  - Calcitonin Gene-related Peptide. The First Decade of a Novel Pleiotropic
      Neuropeptide. Proceedings of an International Symposium. Graz, Austria, July 28
      31, 1991.

PMID- 1353339
TI  - Immunoneutralization studies with calcitonin gene-related peptide.

PMID- 1353340
TI  - Late-onset metachromatic leukodystrophy: molecular pathology in two siblings.
AB  - We report on a new allele at the arylsulfatase A (ARSA) locus causing late-onset
      metachromatic leukodystrophy (MLD). In that allele arginine84, a residue that is
      highly conserved in the arylsulfatase gene family, is replaced by glutamine. In
      contrast to alleles that cause early-onset MLD, the arginine84 to glutamine
      substitution is associated with some residual ARSA activity. A comparison of
      genotypes, ARSA activities, and clinical data on 4 individuals carrying the
      allele of 81 patients with MLD examined, further validates the concept that
      different degrees of residual ARSA activity are the basis of phenotypical
      variation in MLD.

PMID- 1353341
TI  - Creutzfeldt-Jakob disease cosegregates with the codon 178Asn PRNP mutation in
      families of European origin.
AB  - We recently discovered an amino acid-altering heterozygous mutation in codon 178
      of the PRNP amyloid precursor gene in patients with familial Creutzfeldt-Jakob
      disease. This mutation is now shown to be associated with the occurrence of
      disease in 7 unrelated families of Western European origin, among which a total
      of 65 members are known to have died from Creutzfeldt-Jakob disease. The mutation
      was detected in each of 17 tested patients, including at least 1 affected member
      of each family, and in 16 of 36 of their first-degree relatives, but not in
      affected families with other mutations, patients with the nonfamilial form of the
      disease, or 83 healthy control individuals. Linkage analysis in two informative
      families yielded a lod score of 5.30, which, because no recombinants were found,
      strongly suggests that codon 178Asn is the actual disease mutation.

PMID- 1353342
TI  - Phenotypic characteristics of familial Creutzfeldt-Jakob disease associated with
      the codon 178Asn PRNP mutation.
AB  - A group of 43 patients from seven families affected by Creutzfeldt-Jakob disease
      (CJD) with the codon 178Asn mutation of the PRNP amyloid precursor gene is
      compared to a group of 211 patients with the sporadic form of the disease. As a
      group, the patients with the codon 178Asn mutation had an earlier age at onset of
      illness (almost always presenting as an insidious loss of memory), a longer
      duration of illness, and an absence of periodic electroencephalographic activity.
      Transmission of disease to primates was accomplished using brain tissue
      homogenates from 6 of 10 patients, resulting in significantly shorter incubation
      periods than those due to sporadic CJD inocula. These findings are interpreted
      and discussed in terms of possible differences in the temporospatial evolution of
      damage to the brain, and of accelerated induction of polymerized amyloid protein
      by its mutationally altered template precursor.

PMID- 1353343
TI  - GM1 gangliosidosis in adults: clinical and molecular analysis of 16 Japanese
      patients.
AB  - Clinical findings were compared with the results of molecular analysis in 16
      Japanese patients from 10 unrelated families with the adult/chronic form of GM1
      gangliosidosis. Age of onset ranged from 3 to 30 years. Major clinical
      manifestations were gait and speech disturbances caused by persistent muscle
      hypertonia. Dystonic postures and movements, facial grimacing, and parkinsonian
      manifestations were commonly seen. Cerebellar signs, myoclonus, severe
      intellectual impairment, dysmorphism, or visceromegaly were not observed. A
      common single-base substitution, 51Ile(ATC)----Thr(ACC), reported in a previous
      study of ours, was confirmed in 14 patients by the Bsu36I restriction site
      analysis; one was a compound heterozygote with another mutation (457Arg[CGA]---
      Gln[CAA]) and the others were homozygotes of this mutation. Clinically, the
      compound-heterozygous patient showed more severe neurological manifestations and
      a more rapid clinical course than those of homozygotes. The homozygotes showed
      considerable variations in the age of onset and subsequent clinical course. The
      51Ile----Thr mutant allele expressed a significant amount of beta-galactosidase
      activity, whereas the 457Arg----Gln mutant allele expressed extremely low
      activity in human GM1 gangliosidosis fibroblasts. We conclude that these gene
      mutations causing different residual enzyme activities are related to the
      severity of clinical manifestations, but some other genetic or environmental
      factors contribute to clinical heterogeneity. The Bsu36I restriction site
      analysis was performed in 7 families and provided clear results for the diagnosis
      of heterozygotes as well as homozygotes of this specific clinical form of GM1
      gangliosidosis. The technique is applicable to prenatal diagnosis and genetic
      counseling.

PMID- 1353344
TI  - Uncommon phenotype for a codon 178 mutation of the human PrP gene.

PMID- 1353346
TI  - Surgical reconstruction of an ascending aortic dissection in Takayasu's
      arteritis.
AB  - A 45-year-old Japanese woman with Stanford type A dissecting aortic aneurysm
      underwent a reconstructive operation on the ascending aorta. Histopathological
      diagnosis was Takayasu's arteritis in the chronic and inactive phase. It is very
      rare that a dissecting aortic aneurysm results from Takayasu's arteritis. Long
      standing hypertension and fragility of the aortic media due to disruption of
      elastic fibers were suspected to cause dissection in the entire aorta in this
      case.

PMID- 1353345
TI  - Assessment of genetic diversity and population structure of Xanthomonas oryzae
      pv. oryzae with a repetitive DNA element.
AB  - A repetitive DNA element cloned from Xanthomonas oryzae pv. oryzae was used to
      assess the population structure and genetic diversity of 98 strains of X. oryzae
      pv. oryzae collected between 1972 and 1988 from the Philippine Islands. Genomic
      DNA from X. oryzae pv. oryzae was digested with EcoRI and analyzed for
      restriction fragment length polymorphisms (RFLPs) with repetitive DNA element as
      a probe. Twenty-seven RFLP types were identified; there was no overlap of RFLP
      types among the six races from the Philippines. Most variability (20 RFLP types)
      was found in strains of races 1, 2, and 3, which were isolated from tropical
      lowland areas. Four RFLP types (all race 5) were found among strains isolated
      from cultivars grown in the temperate highlands. The genetic diversity of the
      total population of X. oryzae pv. oryzae was 0.93, of which 42% was due to
      genetic differentiation between races. The genetic diversities of strains
      collected in 1972 to 1976, 1977 to 1981, and 1982 to 1986, were 0.89, 0.90, and
      0.92, respectively, suggesting a consistently high level of variability in the
      pathogen population over the past 15 years. Cluster analysis based on RFLP
      banding patterns showed five groupings at 85% similarity. The majority of strains
      from a given race were contained within one cluster, except for race 3 strains,
      which were distributed in three of the five clusters.

PMID- 1353347
TI  - Periodontal bone loss in mice induced by different periodontopathic organisms.
AB  - Periodontal bone loss in mice orally inoculated with Peptostreptococcus
      anaerobius, Pept. magnus and Actinobacillus actinomycetemcomitans was compared to
      that in sham-inoculated mice. Six-to-8-week-old BALB/c mice were inoculated with
      1 x 10(5), 1 x 10(7) or 1 x 10(9) colony-forming units (c.f.u.) of bacteria in 50
      microliters of medium. Ten mice received each concentration of bacteria and 10
      sham-inoculated mice acted as controls. Five mice from each of the groups were
      killed 6 weeks after inoculation and the remaining five mice at 12 weeks. Right
      hemimandibles were defleshed, stained and bone loss was measured using an image
      analyser. All the organisms tested were associated with bone loss. Animals that
      had received Pept. anaerobius and Pept. magnus had up to 18% more bone loss than
      those sham inoculated. In contrast, mice inoculated with A. actinomycetemcomitans
      had up to 38% more bone loss than the sham-inoculated animals, this amount of
      loss occurring at the lowest inoculation of 1 x 10(5) c.f.u. These data
      demonstrate a differential ability of micro-organisms to cause periodontal bone
      loss in mice.

PMID- 1353350
TI  - Hemodynamic responses and activity tolerance to stair climbing during the second
      week post-myocardial infarction.
AB  - The purpose of this study was to evaluate the hemodynamic responses and activity
      tolerance to stair climbing of second week post-myocardial infarction (MI)
      patients. Forty MI patients were stratified into beta-blocker medication users
      and non-users and randomly assigned to the experimental or control conditions.
      The 21 experimental subjects performed a walk/stair climb, and the 19 control
      subjects, a walk/stand activity protocol. Changes in heart rate and blood
      pressure from before, to immediately after both the walk/stair and walk/stand
      activity protocols were clinically small. No significant differences existed in
      the distribution of hemodynamic signs among the experimental and control
      subjects. However, proportionately more experimental than control subjects had
      symptoms of activity intolerance (7/21 vs 1/19; p less than 0.05). No correlation
      existed between activity (in) tolerance and either days post-MI or time required
      for stair climbing. Based upon these preliminary findings, assessment of
      tolerance to stair climbing activities is warranted during the second week post
      MI.

PMID- 1353349
TI  - [Current ideas on hay fever and its treatment].
AB  - Etiological treatment of atopic dermatitis cannot be considered without taking
      account of all the data of the syndrome: Search for the etiological; mechanism;
      Treatment of the cause and skin changes; Preventative treatment of infection;
      Above all, treatment of pruritus that determines the final state of the skin by
      the consequent scratching and the future psychological condition from the
      implicated prolonged suffering. Even though it may be difficult, responsible
      allergens must be detected and the entire range of allergy treatments tried. The
      local treatments to give a good skin condition must be understood. Finally, it is
      essential to educate the parents for the best possible family effort.

PMID- 1353348
TI  - Growth-hormone-prolactin interactions in the regulation of mammary and adipose
      tissue acetyl-CoA carboxylase activity and gene expression in lactating rats.
AB  - The factors and mechanisms responsible for the reciprocal changes in lipogenesis
      in rat mammary gland and adipose tissue during the lactation cycle have been
      investigated. Lactation decreased the activation status and mRNA concentration of
      acetyl-CoA carboxylase in adipose tissue. Litter removal decreased the mRNA
      concentration of acetyl-CoA carboxylase in the mammary gland and increased the
      enzyme's mRNA concentration and activation status in adipose tissue. Lowering
      serum prolactin concentration in lactating rats decreased the amount of mammary
      acetyl-CoA carboxylase mRNA and increased that of adipose tissue, and increased
      the activation status of the enzyme in adipose tissue. Decreasing serum growth
      hormone (GH) alone had little effect on acetyl-CoA carboxylase in lactating rats,
      although it did lower pup growth rate and serum concentration of insulin-like
      growth factor-I. Lowering serum GH concentration exacerbated the effects of
      decreasing serum prolactin on mammary-gland (but not adipose-tissue) acetyl-CoA
      carboxylase mRNA and further increased the rise in activation status of the
      adipose-tissue enzyme induced by decreasing serum prolactin. Changes in acetyl
      CoA carboxylase mRNA in both mammary and adipose tissue were paralleled by
      changes in total enzyme activity except after litter removal, when there was a
      disproportionately large decrease in total enzyme activity of the mammary gland.
      Thus prolactin has a major and GH a minor role in the regulation of acetyl-CoA
      carboxylase activity during lactation. Changes in mammary activity in response to
      prolactin and GH are primarily due to alterations in gene transcription, whereas
      adaptation in adipose tissue involves both changes in gene transcription and
      activation status.

PMID- 1353351
TI  - Chronic ethanol treatment of rats and the myocardial beta-adrenoceptors.
AB  - We examined the effect of chronic treatment with ethanol on the dynamics of beta
      adrenoceptor binding in left ventricular myocardium of rats. After treatment with
      BAAM (20 mg/kg i.p.), an irreversible inhibitor of beta-adrenoceptors, the
      inhibition of beta-adrenoceptor binding was less, and the recovery of receptor
      binding was faster in chronically ethanol-treated rats compared to the control
      animals given equicaloric dextrin maltose treatment. When intracellular beta
      adrenoceptor recycling was inhibited with colchicine, cytoplasmic left
      ventricular beta-adrenoceptor binding was greater in ethanol-treated compared to
      dextrin maltose-treated animals. We conclude that the previously reported
      decreased functional activity of the beta-adrenoceptor-mediated system probably
      reflects the contribution of ethanol-mediated effects not entirely restricted to
      the receptor-binding mechanisms.

PMID- 1353352
TI  - The role of growth factors in embryonic induction in Xenopus laevis.
AB  - Establishment of the body pattern in all animals, and especially in vertebrate
      embryos, depends on cell interactions. During the cleavage and blastula stages in
      amphibians, signal(s) from the vegetal region induce the equatorial region to
      become mesoderm. Two types of peptide growth factors have been shown by explant
      culture experiments to be active in mesoderm induction. First, there are several
      isoforms of fibroblast growth factor (FGF), including aFGF, bFGF, and hst/kFGF.
      FGF induces ventral, but not the most dorsal, levels of mesodermal tissue; bFGF
      and its mRNA, and an FGF receptor and its mRNA, are present in the embryo. Thus,
      FGF probably has a role in mesoderm induction, but is unlikely to be the sole
      inducing agent in vivo. Second, members of the transforming growth factor-beta
      (TGF-beta) family. TGF-beta 2 and TGF-beta 3 are active in induction, but the
      most powerful inducing factors are the distant relatives of TGF-beta named
      activin A and activin B, which are capable of inducing all types of mesoderm. An
      important question relates to the establishment of polarity during the induction
      of mesoderm. While all regions of the animal hemisphere of frog embryos are
      competent to respond to activins by mesoderm differentiation, only explants that
      include cells close to the equator form structures with some organization along
      dorsoventral and anteroposterior axes. These observations suggest that cells in
      the blastula animal hemisphere are already polarized to some extent, although
      inducers are required to make this polarity explicit.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1353353
TI  - TGF-beta family factors in Drosophila morphogenesis.
AB  - Many Drosophila genes have now been identified with substantial sequence
      similarity to vertebrate protooncogenes and growth factors. Some of these have
      been isolated directly by cross-hybridization with vertebrate probes and some
      have been recognized in the sequences of genes cloned because of their intiguing
      mutant phenotypes. An example of a gene isolated for its interesting development
      functions but with homology to a vertebrate growth factor is the Drosophila
      decapentaplegic gene (dpp). An example of a Drosophila gene isolated by virtue of
      its sequence conservation is the vgr/60A gene. Both dpp and vgr/60A are members
      of the transforming growth factor-beta family and are most similar to the human
      bone morphogenetic proteins. The regulation of the dpp gene by several different
      groups of pattern formation genes including the dorsal/ventral group, the
      terminal group, the segment polarity genes, and the homeotic genes indicates that
      many events in embryogenesis require the cell to cell communication mediated by
      the secreted dpp protein. The temporal and spatial pattern of vgr/60A expression
      differs from that of dpp indicating that it may be regulated by different pattern
      information genes. The experimental advantages of the Drosophila system should
      permit a better understanding of the importance of growth factor homologs in
      specific developmental events, aid in establishing the functional interactions
      between these regulatory molecules, and identify new genes that are important for
      the biological functions of growth factors. It is likely that some of the newly
      identified genes will have vertebrate homologs and the analysis of these may be
      helpful in studies on vertebrate development and tumor biology.

PMID- 1353354
TI  - TGF-beta and related proteins in development, an MCDB/ISU symposium. Ames, Iowa,
      September 20-23, 1991.

PMID- 1353355
TI  - Intrathecal diamorphine-bupivacaine during labour.

PMID- 1353356
TI  - Probable resistance to vecuronium involving the 17-hydroxy metabolite.

PMID- 1353357
TI  - [Italian Association of Visceral Synthesis and Mini-Invasive Surgery, 3rd
      National Congress. Ischia, May 26-28, 1991].

PMID- 1353358
TI  - ["Telescopic" pancreatico-jejunal anastomosis after duodenocephalopancreatectomy
      for cancer].
AB  - The Authors report their experience and a review of the literature on the
      "telescopic" pancreatojejunostomy following pancreatoduodenectomy. The
      alternative modalities proposed for the management of the pancreatic stump and
      their results are also described. Although no technique seems free from
      complications, the relatively low rate of anastomotic leaking (7.9%) encountered
      convinced the Authors to adopt this technique on routine basis.

PMID- 1353359
TI  - [Duodenocephalopancreatectomy with preservation of the pylorus in ampullary
      cancer].
AB  - The Authors report their experience in the surgical management of ampullary
      cancer using the Longmire-Traverso technique of pancreatoduodenectomy with
      pylorus preservation. They consider this operation as the most functional in
      restoring digestive continuity.

PMID- 1353360
TI  - ["Telescopic" terminoterminal pancreatico-jejunal anastomosis after
      duodenocephalopancreatectomy].
AB  - Pancreaticojejunostomy represents the most important step of the reconstructive
      process following pancreaticoduodenectomy. Anastomotic dehiscence at this level
      accounts for two thirds of total postoperative mortality. In order to reduce the
      incidence of anastomotic complications, we have recently adopted a new technique
      of "telescopic" end-to-end-pancreaticojejunostomy where, differently from our
      previous technique, we are not any longer invaginating the small bowel over the
      pancreatic stump. Our preliminary results obtained in 5 consecutive patients
      appear to be promising.

PMID- 1353361
TI  - [Personal trends concerning pancreatic head or periampullary neoplasms].
AB  - On the basis of his recent experience with twelve consecutive cases of
      periampullary or pancreatic head carcinoma, the Author reports on some technical
      aspects of reconstruction following pancreaticoduodenectomy. Preference is
      expressed for the end-to-end jejunopancreatic anastomosis of the residual stump
      as this act never caused significant complications.

PMID- 1353362
TI  - [Jejunal mucosectomy as a preliminary technique of pancreatico-jejunal
      anastomosis].
AB  - The Authors describe mucosectomy as a preliminary technique to pancreatico
      jejunal anastomosis. The removal of the last few centimeters of the jejunal
      mucosa enhances the perfect adhesion of the loop to the pancreatic parenchyma.
      Results seem to confirm theory: in our experience, "telescopic" technique
      associated with mucosectomy and somatostatin administration prevented so far
      anastomotic leakages.

PMID- 1353363
TI  - [Immediate and early results in pancreatic resections using a stapler].

PMID- 1353364
TI  - Cell proliferation of transitional cell bladder tumours determined by PCNA/cyclin
      immunostaining and its prognostic value.
AB  - Cell proliferation of transitional cell bladder cancer (TCC) was determined by
      PCNA (proliferating cell nuclear antigen)/cyclin immunostaining in 178 TCCs and
      the results were related to established prognostic factors, progression and
      survival during a mean follow-up period of 10 years. The fraction of PCNA/cyclin
      positive nuclei was related to T-category (P = 0.008), papillary status, WHO
      grade, DNA ploidy, S phase fraction, M/V index (volume corrected mitotic index)
      and AgNORs (silver stained nucleolar organiser regions) (for all P less than
      0.001). TCCs presenting with pelvic lymph node metastasis at diagnosis had a
      significantly higher growth fraction than the tumours confined to the bladder
      wall (P less than 0.001). The fraction of PCNA/cyclin positive nuclei predicted
      progression in T-, N- and M-categories (P less than 0.001). In Ta-T1 tumours high
      fraction of PCNA/cyclin positive nuclei predicted metastasis (P = 0.019). In
      survival analysis the fraction of PCNA/cyclin positive nuclei predicted survival
      in the entire cohort (P less than 0.001) and in Ta-T1 tumours (P = 0.0005). In a
      multivariate survival analysis the fraction of PCNA/cyclin positive nuclei showed
      independent predictive value in the entire cohort (P = 0.046), in papillary
      tumours (P = 0.006) and in Ta-T1 tumours (P = 0.015). The results show that the
      growth fraction as determined by PCNA/cyclin immunostaining is a significant
      prognostic variable in TCC.

PMID- 1353365
TI  - Large-scale culture system of human CD4+ helper/killer T cells for the
      application to adoptive tumour immunotherapy.
AB  - A simple method for the rapid expansion of human CD4+ T cells with both helper
      and killer functions was established. CD4+ T cells separated from peripheral
      blood mononuclear cells using immunomagnetic beads were stimulated with
      immobilised OKT-3 monoclonal antibody (mAb) plus recombinant interleukin 2 (rIL
      2) in 96 well culture plates. After 6 day-culture, the CD4+ T cells were
      restimulated by immobilised OKT-3 mAb for an additional 24 h, then inoculated
      into concentrated rotary-tissue culture bag and cultured for further 9 days. This
      procedure yielded a 3000-fold increase in cell number (about 3-5 x 10(9) per
      bag). Most of the cells (over 96%) continued to express CD4+ antigen and retained
      their capacity to produce IL-2. The activated CD4+ T cells showed marked
      cytotoxicity against Fc receptor positive tumour cells in the presence of OKT-3
      mAb. Moreover, we succeeded in a specific targeting of the expanded CD4+
      helper/killer T cells to c-erb B-2 positive tumour cells by means of anti-CD3 x
      anti-c-erb B-2 bispecific antibody. These results suggested that our established
      simple system will be available for the expansion of large number of CD4+
      helper/killer T cells which may provide an efficient strategy for adoptive tumour
      immunotherapy.

PMID- 1353366
TI  - Bucindolol, a beta blocker, decreased ventricular fibrillation and maintained
      mechanical function in a pig model of acute myocardial ischemia.
AB  - Bucindolol is a new beta blocker with marked vasodilatory properties and
      intrinsic sympathomimetic activity. We tested its potential effect against
      ventricular fibrillation (VF), in a pig model of acute myocardial ischemia.
      Bucindolol 6 mg/kg IV was administered in two equally divided doses, the first 30
      minutes prior to, and the second 10 minutes after, ligation of the anterior
      descending coronary artery (CAL) in anesthetized open-chest pigs. Bucindolol
      decreased the incidence of VF to 1/11 versus 14/16 in the control group (p less
      than 0.005). Bucindolol also decreased the duration of ventricular tachycardia,
      15 +/- 8 seconds versus 104 +/- 32 seconds in the control group (p less than
      0.01). Bucindolol maintained LVmaxdP/dt at predrug and pre-CAL values, whereas
      LVmaxdP/dt was decreased by CAL in the control group. Bucindolol decreased
      arterial pressure and heart rate. Bucindolol increased blood flow in the
      peripheral ischemic zone (24.6 +/- 1.8% versus 16.2 +/- 1.7% (percent of pre-CAL
      value) in controls, p less than 0.002), as well as in the nonischemic zones
      (periischemic zone: 126.4 +/- 6.1% versus 96.7 +/- 4.8% in the control group, p
      less than 0.0005; remote nonischemic zone: 126.6 +/- 7.1% versus 87.1 +/- 4.3% of
      pre-CAL value in the control group, p less than 0.0001). Bucindolol had marked
      antiarrhythmic effects that were associated with beneficial effects on the
      mechanical function of the left ventricle and on blood flow to the ischemic
      myocardium.

PMID- 1353367
TI  - Exercise tolerance with nebivolol and atenolol.
AB  - Patients treated with beta-blocking agents often complain of fatigue during
      exercise. Exercise capacity is decreased under this condition. Nebivolol is a new
      beta 1-adrenoceptor antagonist with a particular hemodynamic profile, which might
      be due to an ancillary property. Five milligrams once daily seems the optimal
      dose for antihypertensive treatment. In a double-blind, placebo-controlled
      crossover study, the effects of nebivolol on maximal and endurance exercise
      capacity are compared with those of atenolol in healthy volunteers. The
      hemodynamic and metabolic effects during exercise are also studied. Nebivolol 5
      mg once daily and atenolol 100 mg once daily decrease blood pressure at rest
      similarly. At these dosages nebivolol shows a smaller decrease in heart rate than
      atenolol. During exercise, the rise in systolic blood pressure and heart rate is
      less depressed with nebivolol than with atenolol. In contrast to atenolol,
      nebivolol does not decrease maximal and endurance exercise capacity, and does not
      increase perceived exertion significantly. Changes in hemodynamics influence
      maximal exercise capacity. Since nebivolol has less effect on exercise
      hemodynamics than atenolol, this might explain why maximal work capacity is not
      changed during nebivolol. During endurance exercise metabolic effects are thought
      to be more important. Under nebivolol glycerol and NEFA production is less
      depressed during exercise and might explain the preserved endurance capacity.
      These data suggest less beta blockade during nebivolol than during atenolol at
      the dosages used in this study. In conclusion, at a dose known to be
      antihypertensive, nebivolol does not alter exercise capacity significantly in
      healthy volunteers.

PMID- 1353368
TI  - Comparison of bisoprolol and diazepam in the treatment of cardiac neurosis.
AB  - In order to compare the beta blockers bisoprolol and diazepam in the treatment of
      cardiac neurosis, 40 patients (16 males and 24 females, mean age: 39 +/- 11
      years) were examined in a double-blind, crossover study. Following a 4-week
      placebo period, patients were randomized to receive either bisoprolol 10 mg daily
      or diazepam 5 mg twice daily for 4 weeks. After a second 4-week washout period on
      placebo, patients were switched to the alternative regimen for a further 4 weeks.
      At the end of the placebo periods and during each phase of treatment, the
      following parameters were evaluated: somatic symptoms by self-assessment
      questionnaire, anxiety state by Hamilton rating scale, reaction time to both
      acoustic and visual stimuli, blood pressure, and heart rate. Both treatments were
      effective in reducing somatic symptoms of cardiac neurosis, but bisoprolol was
      significantly more effective than diazepam (p less than 0.01). On the contrary,
      diazepam was superior to bisoprolol in improving the Hamilton scale related to
      psychic symptoms. Only diazepam prolonged reaction times. Both treatments were
      well tolerated; however, 12 patients complained of drowsiness and nine of
      sedation under diazepam. In conclusion, bisoprolol appeared to be as effective as
      diazepam in the treatment of cardiac neurosis, but with better effects on somatic
      symptoms and without affecting patients' psychomotor performance.

PMID- 1353369
TI  - The relationship of structural brain imaging parameters to antipsychotic
      treatment response: a review.
AB  - Over the last decade, a number of studies have attempted to relate brain
      morphology to treatment response to neuroleptics. This approach has scientific
      potential to define subtypes of schizophrenia as well as potential clinical
      utility. In the present report, a review of 33 studies, including a meta
      analysis, is provided. Although the overall test of the effect was not
      significant, the analysis revealed marked heterogeneity in the results of the
      various studies. The following factors were significant predictors of effect
      size: age, illness duration and age of onset of the patient cohort, the
      percentage of patients with marked structural abnormality included in the study
      overall, the duration of treatment and the degree of symptom improvement in the
      study overall. The following factors were unrelated to study effect size: date of
      study, gender, and the presence of a washout period. In future studies, attention
      to the parameters utilized in the meta-analysis should help to clarify the
      strength and generality of the relationship between brain morphology and
      treatment response.

PMID- 1353371
TI  - Solution structure of the Lewis x oligosaccharide determined by NMR spectroscopy
      and molecular dynamics simulations.
AB  - The Lewis x (Lex) determinant is a trisaccharide fragment that has been
      implicated as a specific differentiation antigen, as a tumor antigen, and as a
      key component of the ligand for the endothelial leukocyte adhesion molecule, ELAM
      1. High-resolution nuclear magnetic resonance spectroscopy shows it to have a
      relatively rigid structure. Only a small range of glycosidic dihedral angles in
      the trisaccharide produce simulated nuclear Overhauser effect spectra agreeing
      with data measured for the human milk pentasaccharide, lacto-N-fucopentaose-3,
      which contains the Lex determinant. Independently, the same average structure for
      the Lex determinant arises from in vacuo molecular dynamics simulations. The
      proposed conformation of the Lex trisaccharide is very similar to that recently
      determined for the closely related Lea trisaccharide. In agreement with the
      recent finding that both sialylated Lea and Lex react with ELAM-1, the results
      presented here show that the Lea and Lex determinants contain very similar
      carbohydrate domains.

PMID- 1353370
TI  - 50 kD prolactin binding protein in schizophrenics on neuroleptic medication.
AB  - Serum samples from 15 age-matched normal male subjects and 15 male schizophrenic
      patients on neuroleptic medication were subjected to immunoprecipitation with
      anti-human prolactin (PRL) and analysis of the immunoprecipitate by two
      dimensional gel electrophoresis. We report the unexpected immunoprecipitation of
      large amounts of an approximately 50 kD protein in 12/15 of the schizophrenic
      patients. Preliminary analyses suggest that this 50 kD protein may be an IgG
      heavy chain. Since total levels of IgG and each of the IgG subclasses are the
      same in the normal and schizophrenic group, the increased amount of the 50 kD
      protein in the schizophrenics is clearly specific to anti PRL precipitation.
      Since the anti-PRL does not directly recognize either the 50 kD protein or any
      immunoglobulin light chains in the precipitate, we suggest that the 50 kD protein
      is precipitated because it is bound to PRL. Perhaps immunoglobulin binding of PRL
      is a mechanism used to compensate for chronically elevated PRL levels during
      neuroleptic treatment.

PMID- 1353373
TI  - Protein Biosynthesis. Part I. International conference proceedings. Pushchino,
      Russia, August 26-September 23, 1991.

PMID- 1353372
TI  - Lipophilic beta-blockers inhibit monocyte and endothelial cell-mediated
      modification of low density lipoproteins.
AB  - The effects of propranolol, pindolol and metoprolol on the modification of low
      density lipoprotein (LDL) by U937 monocyte-like cells, endothelial cells and
      copper ions were studied by determination of the lipid peroxidation product
      content and measurement of the relative electrophoretic mobility of the particle.
      Propranolol and pindolol inhibited LDL oxidation by U937 cells in a dose
      dependent manner from 10 to 100 microM, whereas metoprolol had no effect. In the
      case of LDL modification by endothelial cells, all the three beta-blockers were
      efficient within the same range of concentrations, and the order of potency was
      propranolol greater than pindolol greater than metoprolol. In vitro oxidation of
      LDL in the presence of copper ions was also inhibited by propranolol; pindolol
      and metoprolol had no significant protective effect in this system. These results
      concerning the inhibitory action of beta-blockers were confirmed by testing the
      degradation of modified LDL by J774 macrophages. Although the concentrations of
      the drugs utilized in this study are relatively high, in long-term treatment beta
      blockers might accumulate in target tissues, and the protective effect of
      propranolol against LDL oxidation might be involved in its inhibitory action on
      atherosclerosis previously reported in animal models.

PMID- 1353374
TI  - Protein biosynthesis. Part II. International conference. Pushchino, Russia, 26
      August-3 September 1991.

PMID- 1353375
TI  - Bone marrow transplantations and viral infections. Symposium. Tubingen, Federal
      Republic of Germany, May 31-June 1, 1991.

PMID- 1353376
TI  - 4-Methoxytranylcypromine, a monoamine oxidase inhibitor: effects on biogenic
      amines in rat brain following chronic administration.
AB  - 4-Methoxytranylcypromine (MeOTCP), a ring-substituted analogue of the monoamine
      oxidase (MAO)-inhibiting antidepressant tranylcypromine (TCP), was investigated
      in the rat after chronic (28-day) administration and the results compared with
      those observed with TCP using equimolar doses of both drugs. At the dose tested,
      MeOTCP produced a greater inhibition of type A MAO in brain, liver, and heart
      than did TCP. Both drugs caused a reduction in the specific binding to beta
      adrenergic and tryptamine receptors in cortex from brain. MeOTCP produced a
      marked increase in 5-hydroxytryptamine levels in pons-medulla, hypothalamus, and
      hippocampus relative to values in vehicle-treated rats and also produced a
      significant increase in these levels over those observed in the TCP-treated rats.

PMID- 1353377
TI  - Antidepressant-like effects of dopamine agonists in an animal model of
      depression.
AB  - Chronic exposure to mild unpredictable stress (CMS) has previously been found to
      cause an antidepressant-reversible decrease in the consumption of palatable sweet
      solutions. There is evidence that the effect of antidepressants in this model is
      mediated by an increase in transmission at dopamine (DA) synpases. The present
      study investigated whether another treatment known to increase the functional
      responsiveness of DA systems, intermittent administration of DA agonists, would
      have antidepressant-like effects. In three experiments in rats, CMS-induced
      decreases in sucrose consumption were reversed by three to four twice-weekly
      injections of quinpirole (100-200 micrograms/kg) or bromocriptine (2.5 mg/kg).
      The effects lasted for several weeks, and when they waned, could be reinstated by
      a single additional injection of quinpirole. As with tricyclic antidepressants,
      the effect of quinpirole was reversed by raclopride, administered acutely
      immediately prior to a sucrose consumption test; there were no changes in sucrose
      intake in nonstressed control animals. The results suggest that intermittent
      administration of DA agonists merits investigation as a novel strategy for the
      treatment of depression.

PMID- 1353378
TI  - Adverse effects of sulphasalazine.

PMID- 1353380
TI  - 2-Chlorodeoxyadenosine: an active agent in the treatment of cutaneous T-cell
      lymphoma.
AB  - Cutaneous T-cell lymphomas are disfiguring malignant lymphoproliferative
      disorders for which standard therapy has been principally palliative. 2
      Chlorodeoxyadenosine (2-CdA), a new purine analogue resistant to degradation by
      adenosine deaminase that has substantial activity against lymphoid neoplasms, was
      administered to 16 patients with cutaneous involvement by T-cell lymphoma. All
      patients had failed topical treatment modalities and/or systemic therapies.
      Fifteen patients were evaluable; one patient was not evaluable due to incomplete
      therapy and follow-up. The overall response rate was 47%. Three of 15 patients
      (20%) achieved complete responses and four of 15 patients (27%) achieved partial
      responses. The median duration of response was 5 months. One patient remains in
      unmaintained complete remission at 52+ months. Therapy was well tolerated.
      Myelosuppression was the principal toxicity encountered, occurring in 8 of 15
      (53%) patients. 2-CdA is an effective new agent for the treatment of cutaneous T
      cell lymphoma and warrants further study both as a single agent and in
      combination regimens.

PMID- 1353379
TI  - Correlation of CD2 expression with PML gene breakpoints in patients with acute
      promyelocytic leukemia.
AB  - The chromosomal translocation t(15;17)(q22:21) of acute promyelocytic leukemia
      (APL) fuses PML, a novel gene, with RAR alpha, a retinoic acid receptor gene. PML
      RAR hybrid transcripts were studied in 18 cases of APL using RNA-PCR. Two forms
      were noted: one designated 5', producing a 439-bp chimeric fragment, and a 3'
      form, producing a pair of fragments of 765 bp and 909 bp. 5' forms were found in
      7 of the 18 cases while the other 11 patients expressed the 3' forms. The
      chromosome 15 specific probes K3 and K2 were used to study genomic breakpoints in
      12 APL patients. Comparison of these results with RNA PCR in 11 patients for whom
      both were available yielded a rearrangement pattern predictive of whether the
      hybrid transcript was 5' or 3'. In this way, an additional three patients in whom
      DNA but not RNA was available were identified as having 3' (downstream)
      breakpoints and, therefore, 3' hybrid forms. Thus, 21 cases categorized as having
      5' or 3' PML-RAR transcripts were analyzed for various phenotypic differences.
      Surface phenotyping of leukemic promyelocytes demonstrated expression of the CD2
      antigen in all cases with the 5' splice variant. Only 1 of 11 cases with the 3'
      form showed CD2 expression. This difference is significant at P = .001.

PMID- 1353382
TI  - Geographic origin of the Y chromosomes in "old" inbred strains of mice.
AB  - Six distinct Y Chromosomes (Chr) were identified among 39 standard inbred strains
      of mice with five probes that identified Y Chr-specific restriction fragments on
      Southern blots. Three Y Chr types, distributed among 31 strains, were of Asian
      Mus musculus origin. The remaining three Y Chr types, distributed among eight
      strains, were of M. domesticus origin. The Asian source of the M. musculus Y Chr
      was confirmed by determining the DNA sequence of 221 bp from an open reading
      frame within the Sry (sex determining region Y) gene (Gubbay et al., Nature 346:
      245-250, 1990) in three inbred strains (C57BL/6J, AKR/J, and SWR/J) and comparing
      the sequence to the homologous sequences derived from wild caught European and
      Asian M. musculus males. These data indicate that a minimum of six male mice
      contributed to the formation of the old inbred strains.

PMID- 1353381
TI  - Morphometric evaluation of populations of neuronal profiles (cell bodies,
      dendrites, and nerve terminals) in the central nervous system.
AB  - Morphometric techniques have been developed to quantitatively characterize groups
      of transmitter-identified neuronal profiles, such as cell groups, dendrite and
      nerve terminal fields. These morphometric techniques will be illustrated by
      introducing some general tools for image analysis which can be considered as a
      background for the present specific applications. The following methods have been
      included: (1) methods to identify and quantitatively characterize, from both
      numerical and geometrical standpoints, groups of profiles in a two- and three
      dimensional frame; (2) methods to evaluate the evenness of a certain distribution
      of profiles in the plane; (3) methods to identify subgroups of profiles based on
      their different spatial or optical density; and (4) methods to compare the
      distributions of two or more groups of profiles. The applications of these
      general tools to some neuroanatomical problems, such as cell group definition and
      description, have been illustrated. Practical examples performed on
      immunocytochemical preparations of neuronal profile populations are also given.
      Finally, the potentiality of numerical classification to classify and compare
      morphometric data has been shown. As an example, numerical classification methods
      have been applied to the morphometric and microdensitometric analysis of
      adrenaline/neuropeptide Y costoring neuronal systems of the brainstem in adult
      and aged rats.

PMID- 1353383
TI  - The gene for proliferating cell nuclear antigen (Pcna) maps to mouse chromosome
      2.
AB  - The structural gene for proliferating cell nuclear antigen (Pcna) has been mapped
      to mouse Chromosome (Chr) 2 by use of a PCR-based assay. With somatic cell
      hybrids, Pcna was mapped between the T(2;4)13H and T(2;4)1Sn breakpoints. An
      interspecific backcross was employed to map Pcna 1.9 +/- 1.3 cM distal to Il-lb.
      This was confirmed by mapping Pcna in the BXH recombinant inbred (RI) strains; no
      recombinants were seen between Il-la and Pcna. In addition, a PCNA-related
      sequence (Pcna-rsl) was mapped to Chr 19 in the BXH RI strains.

PMID- 1353385
TI  - Clinical Autonomic Research Society Proceedings. Abstracts.

PMID- 1353384
TI  - The vasodilating effect of spinal dorsal column stimulation is mediated by
      sympathetic nerves.
AB  - Spinal dorsal column stimulation has been used in the treatment of a patient with
      a painful vasospastic condition in the right arm following surgical sympathectomy
      on the left side. After sympathectomy the left arm became constantly dry and warm
      and consistently lacked skin vasomotor (laser Doppler flowmetry) responses to
      arousing stimuli, indicating a complete loss of sympathetic vasomotor
      innervation. The return of minimal sudomotor (skin resistance) responses to
      mental stress 2 years after sympathectomy indicated a partial reinnervation of
      sweat glands. Immediately after sympathectomy, the contralateral right arm became
      increasingly cold and cyanotic and the patient complained of chronic painful
      coldness and severe cold-intolerance in the right arm. Attempts to
      pharmacologically vasodilate the arm with felodipine did not affect the local
      vasoconstriction and pain. Dorsal column stimulation (associated with symmetrical
      paraesthesia in both arms) induced an immediate and marked (ten-fold) increase in
      skin blood flow in the right arm (and in the leg), whereas skin blood flow in the
      left arm remained unaffected. The lack of vasomotor response in the left arm was
      not due to maximal vasodilatation at rest, since skin blood flow in the left arm
      showed a normal capacity for axon reflex vasodilatation following antidromic
      activation of sensory afferents. The results suggest that the marked
      vasodilatation induced by dorsal column stimulation is mediated by sympathetic
      vasomotor fibres, via modulation of central neuronal circuits involved in the
      regulation of skin sympathetic discharge.

PMID- 1353386
TI  - A study of the alpha-1 adrenoceptor blocker prazosin in the prophylactic
      management of autonomic dysreflexia in high spinal cord injury patients.
AB  - The ability of the alpha-1 adrenoceptor antagonist, prazosin, to reduce the
      severity and duration of episodes of autonomic dysreflexia was studied in
      cervical and high thoracic spinal cord injury patients with documented episodes
      of autonomic dysreflexia. Sixteen patients participated in a double blind
      parallel group study comparing prazosin 3 mg b.d. with placebo given for 2 weeks.
      Both groups were matched for age, sex and baseline severity of autonomic
      dysreflexia episodes. Prazosin was well tolerated and did not produce a
      significant lowering of resting blood pressure. Compared to baseline
      measurements, patients allocated to prazosin therapy were found to have fewer
      severe episodes of autonomic dysreflexia and during these episodes to have
      significant reductions in average rise in systolic and diastolic blood pressure,
      symptom duration and requirement for acute antihypertensive medication. The
      severity of headache during individual autonomic dysreflexia episodes was also
      diminished with prazosin therapy. No symptom parameter was significantly altered
      by placebo therapy. It is concluded that prazosin is superior to placebo in the
      prophylactic management of autonomic dysreflexia and that these findings are
      consistent with suggestions that alpha-1 adrenoceptors play an important role in
      the pathogenesis of this syndrome.

PMID- 1353387
TI  - Thrombospondin: a new attachment protein in preretinal traction membranes.
AB  - Thrombospondin (TSP), an adhesive integrin-binding protein of plasma and
      platelets, was detected in preretinal traction membranes from patients with
      idiopathic (8/8) and traumatic (7/8) proliferative vitreoretinopathy (PVR) and
      proliferative diabetic retinopathy (PDR) (6/8). TSP immunoreactivity was compared
      to the pattern of von Willebrand factor, plasma transglutaminase (blood
      coagulation factor XIII), fibronectin, and mononuclear phagocytes, using double
      label immunofluorescence microscopy. TSP was partially colocalised with the
      endothelial cell marker, von Willebrand factor, in PDR. The codistribution of
      catalytic factor XIII and two cross-linking substrates, fibronectin and TSP,
      suggests a functional role of the enzyme in the extracellular matrix build-up in
      PVR and PDR. No significant TSP synthesis by mononuclear phagocytes was observed.
      Western blotting indicated a plasmin-mediated intravitreal breakdown of
      presumably plasmatic TSP in PVR and PDR.

PMID- 1353388
TI  - Early clinical results with the neuroleptic roxindole (EMD 49,980) in the
      treatment of schizophrenia--an open study.
AB  - The neuroleptic effect and tolerability of roxindole (EMD 49,980), an agonist of
      the dopamine-D2 autoreceptor, was studied during a 4 week treatment period in 7
      patients with paranoid-hallucinatory schizophrenia (ICD-9: 295.3). In patients
      with a daily dosage of up to 4.5 mg/day, there was no improvement as measured
      with the total score of the BPRS scale. In contrast, patients with a daily dosage
      of up to 30 mg/day showed a slight improvement, especially in items associated
      with negative symptoms. In 3 patients there were slight adverse events
      (dizziness, hypersalivation, hypotonia, nausea/vomiting, miction disturbance)
      which were probably connected with the intake of roxindole.

PMID- 1353389
TI  - Acute renal failure after ecstasy.

PMID- 1353390
TI  - Ecstasy and the dance of death.

PMID- 1353392
TI  - Neural changes in acute arthritis in monkeys. II. Increased glutamate
      immunoreactivity in the medial articular nerve.
AB  - Glutamate and other excitatory amino acids have been shown to play a key role in
      nociception and the hyperalgesia associated with the acute inflammatory response.
      In an effort to understand more fully the role of Glu in this process, we
      determined that there is Glu in a percentage of axons in the medial articular
      nerve (MAN) of monkeys, a source of preterminal afferent fibers innervating the
      knee joint. After induction of the experimental knee joint inflammation with a
      kaolin/carrageenan mixture, comparison was made of the percentage of Glu positive
      axons in the MAN on the side of the inflammation versus the contralateral MAN
      using post-embedding immunogold electron microscopic methods. A doubling in the
      percentage of Glu-containing axons was observed on the side of the experimental
      arthritis as compared to the MAN of the other side or of uninjected controls. Glu
      positive axons were unmyelinated or were included in the small, thinly myelinated
      group in control nerves. Following induction of the inflammation, axonal diameter
      measurements revealed an increase in Glu content primarily in the small, thinly
      myelinated axons, which correspond to the group III afferent fibers. These
      increases were observed in the anesthetized preparation only when injection of
      kaolin/carrageenan was combined with joint flexion and mechanical stimulation.
      The dramatic increase in percentages of fibers stainable for Glu in the MAN
      following the induction of inflammation suggests that Glu content is greatly
      increased in the afferent fibers and may be a major contributor to the enhanced
      responses of sensory neurons in inflammatory states such as arthritis.

PMID- 1353394
TI  - Undescended testis--the need for a standard classification.

PMID- 1353393
TI  - Absence of prion protein mutation in bipolar manic-depressive patients.

PMID- 1353391
TI  - Neurotransmitter release: facilitation and three-dimensional diffusion of
      intracellular calcium.
AB  - In order to account for the time courses of both evoked release and facilitation,
      in the framework of the Ca2+ hypothesis, Fogelson and Zucker (1985, Biophys. J.
      48, 1003-1017) suggested treating diffusion of Ca2+, once it enters through the
      Ca2+ channels, as a three-dimensional process (three-dimensional diffusion
      model). This model is examined here as a refined version of the "Ca(2+)-theory"
      for neurotransmitter release. The three-dimensional model was suggested to
      account for both the time course of release and that of facilitation. As such, it
      has been examined here as to its ability to predict the dependence of the
      amplitude and time course of facilitation under various experimental conditions.
      It is demonstrated that the three-dimensional diffusion model predicts the time
      course of facilitation to be insensitive to temperature. It also predicts the
      amplitude and time course of facilitation to be independent of extracellular Ca2+
      concentration. Moreover, it predicts that inhibition of the [Na+]o in equilibrium
      with [Ca2+]i exchange does not alter facilitation. These predictions are not
      upheld by the experimental results. Facilitation is prolonged upon reduction in
      temperature. The amplitude of facilitation declines and its duration is prolonged
      upon increase in extracellular Ca2+ concentration. Finally, inhibition of the
      [Na+]o in equilibrium with [Ca2+]i exchange prolongs facilitation but does not
      alter the time course of evoked release after an impulse.

PMID- 1353395
TI  - Laparoscopic excision of an intra-abdominal testis.

PMID- 1353396
TI  - Ten-year review of treatment of the undescended testis in the west of Ireland.
AB  - Advances continue to be made in the treatment of the undescended testis, and
      treatment recommendations are continually changing. We reviewed 543 patients
      admitted for treatment of undescended testes in the 10-year period 1977 to 1986.
      The side and position of the testis were recorded, the patient's age at operation
      and the procedure carried out. The presence of an associated inguinal hernia was
      noted. The necessity for reoperation was recorded and predisposing factors
      sought. We found the mean age at operation to be 9.5 years and this decreased
      significantly over the study period. Dartos pouch orchiopexy was the commonest
      operation (69%). No significant link was found between the procedure performed or
      the presence of a hernia and the need for further procedures; 2.7% of patients
      required such further procedures. A coherent classification of position is
      lacking for abnormally descended testes. We report a classification which we used
      to tackle this situation.

PMID- 1353397
TI  - Surgical outcome of orchiopexy. I. Previously unoperated testes.
AB  - A total of 1209 undescended testes in 961 boys who had no previous surgery for
      this problem have been reviewed with particular regard to the outcome of surgery
      in relation to the pre-operative and intra-operative assessment of the position
      of the testis. A third of impalpable testes were found at operation in the
      abdomen, a third in the inguinal canal and a quarter in the superficial inguinal
      pouch; 1% of all testes and 7% of impalpable testes were absent; 96% of all
      testes reached the scrotum at operation and this figure included 69% of abdominal
      and 94% of canalicular testes. In all 24 testes were excised--7 of which were
      abdominal, 8 canalicular and 9 were in the superficial inguinal pouch. The
      generalisation that the higher the undescended testis before operation the poorer
      the result, does not always hold true.

PMID- 1353398
TI  - Activation of kappa-opioid receptors inhibits depolarisation-evoked exocytosis
      but not the rise in intracellular Ca2+ in secretory nerve terminals of the
      neurohypophysis.
AB  - Nerve endings of the magnocellular neurohypophysial neurones possess kappa-opioid
      receptors. Using a preparation of isolated terminals from the neurohypophysis we
      studied kappa-opioid effects on secretion of oxytocin and vasopressin and on
      intracellular Ca2+ concentration ([Ca2+]i) measured fluorimetrically or using
      digital video imaging with Fura-2. The dihydropyridine Ca(2+)-channel antagonist
      nicardipine reduced [Ca2+]i responses to K(+)-depolarisation (30-40 mM K+) by 55
      75% and inhibited evoked secretion of oxytocin and vasopressin to a similar
      extent. The selective kappa-receptor agonist D-Pro10 Dynorphin A 1-11 (DPDYN)
      substantially inhibited K+ evoked secretion of oxytocin by 40-90% and secretion
      of arginine vasopressin (AVP) by 20-50%. DPDYN caused only a 10% reduction in the
      average total population [Ca2+]i response to K+ depolarisation. No sub-population
      of inhibitory responses was observed when samples of individual terminal [Ca2+]i
      responses were examined with imaging. Although kappa-receptors are coupled to
      Ca(2+)-channels at neuronal somata our data suggest that alternative effector
      mechanisms operate in these secretory nerve endings.

PMID- 1353399
TI  - Neuroprotective effects of phenyl-t-butyl-nitrone in gerbil global brain ischemia
      and in cultured rat cerebellar neurons.
AB  - We examined the ability of phenyl-t-butyl-nitrone (PBN), an electron spin
      trapper, to attenuate ischemia-induced forebrain edema and hippocampal CA1
      neuronal loss in gerbils, and to protect rat cerebellar neurons in primary
      culture from glutamate-induced toxicity. PBN, given i.p. at 75 or 150 mg/kg 30
      min before ischemia (5 min occlusion), increased survival (at 7 days) of CA1
      neurons from 60 +/- 14 (vehicle-treated, n = 17) to 95 +/- 15 (P less than 0.05,
      n = 15) and 145 +/- 3 (P less than 0.01, n = 15), respectively. When gerbils were
      treated with PBN (50 mg/kg, i.p.) immediately and 6 h after reperfusion, followed
      by b.i.d. for an additional 2 days, CA1 neurons survival improved from 35 +/- 9
      (vehicle, n = 20, 6 min occlusion) to 106 +/- 17 (P less than 0.01, n = 13). In
      gerbils exposed to a more severe ischemia (10 min), pretreatment with 150 mg/kg
      PBN increased the survival of CA1 neurons from 6 +/- 6 (vehicle) to 27 +/- 10 (P
      less than 0.05, n = 11). Pretreatment with PBN, at 150 mg/kg, reduced forebrain
      edema (following 15 min ischemia) by 24.7% (P less than 0.01, n = 16). PBN at 50
      mg/kg, i.p. had no hypothermic effect and at 75 or 150 mg/kg caused a transient
      hypothermia. The presence of PBN in the brain was confirmed in microdialysis
      samples and brain tissue extract using HPLC. In vitro, PBN protected rat
      cerebellar neurons against 100 microM glutamate-induced toxicity with an EC50
      value of 2.7 mM. Our results further support the concept that free radicals
      contribute to brain injury following ischemia and suggest the potential
      therapeutic application of electron spin trappers in stroke.

PMID- 1353400
TI  - Glycine response in isolated dorsal cochlear nucleus of C57BL/6J mouse.
AB  - Pharmacological properties of glycine (Gly)-induced Cl- current (ICl) in the
      dorsal cochlear nucleus (DCN) neurons acutely dissociated from C57BL/6J mouse
      were investigated in the whole-cell configuration of the patch-clamp technique.
      Gly-induced ICl increased in a sigmoidal manner with higher Gly concentrations.
      Strychnine blocked the Gly response competitively at low and non-competitively at
      high concentrations. Both glutamate (Glu) and N-methyl-D-aspartate (NMDA)
      responses were augmented by adding 10(-6) M Gly, at which concentration Gly did
      not induce any ICl. This facilitation was not affected by strychnine. Our results
      clearly show the existence of strychnine-sensitive and -insensitive glycine
      receptors in the DCN neurons.

PMID- 1353401
TI  - Voltage-gated potassium current and resonance in the toadfish saccular hair cell.
AB  - Resonance of the membrane potential in response to a perturbing current has been
      demonstrated in sensory hair cells of many acoustico-lateralis systems and
      modelled as the result of the interaction of passive membrane properties and the
      magnitude and kinetics of activation and deactivation of an outward calcium
      activated potassium current (IKCa) and an inward calcium current (ICa). However,
      the majority of the hair cells of the toadfish saccule have, in addition to IKCa,
      a voltage-gated potassium current (IK) active in the same membrane potential
      range as IKCa but with considerably slower activation and deactivation kinetics.
      Additionally, some of these cells have an A current (IA). In the present work,
      the resonance of cells with these three outward potassium currents were compared
      with those from cells containing only IKCa. Hair cells with only IKCa produced a
      high-quality factor (Q) resonance with symmetrical ringing at current onset and
      termination. In many cells having the IK, resonance could be evoked as a high Q
      ringing only at the onset of the current pulse. The resonance at command onset
      was dependent on the presence of IKCa and could be converted into a spike by
      blocking the IKCa with TEA. Some hair cells with IKCa and IK produced spikes
      rather than resonance at all holding potentials tested. This spiking was seen in
      cells with low levels of IKCa or slowly activating IKCa and with cells with IA.
      The presence of cells with such different response modes implies a difference
      between hair cells in their role in sensory coding.

PMID- 1353402
TI  - Chronic exposure to alcohol during development alters the responses to excitatory
      amino acids in cultured Purkinje neurons.
AB  - The effects of chronic alcohol exposure during development on the responses
      evoked by glutamate and the selective excitatory amino acid receptor agonists
      quisqualate (Quis) and kainate were studied in cultured cerebellar Purkinje
      neurons. The cultures were treated with 22 mM or 44 mM ethanol continuously for
      one or two weeks during the main period of morphological and physiological
      development. Extracellular recordings used for most studies characterized the
      responses to all 3 agonists as initial increase in simple spike firing, usually
      including a period of burst activity, followed by reduced activity or total
      inhibition, then return to control firing pattern. Analysis of these responses
      and background spontaneous activity showed several significant differences
      between control and ethanol treated Purkinje neurons. Background spontaneous
      firing, agonist evoked firing, the initial period of activity of the response to
      Quis, and the inhibitory period of the response to glutamate were all
      significantly reduced in the chronically treated neurons; the inhibitory period
      of the response to kainate was significantly increased. In contrast to the
      effects of chronic ethanol exposure, acutely administered ethanol significantly
      increased background spontaneous firing and the inhibitory period of the response
      to Quis. Thus, administering both acute and chronic ethanol altered the responses
      evoked by excitatory amino acids in the developing Purkinje neurons. The effect
      of chronic ethanol exposure on some response components was similar for all
      agonists tested and may be linked to changes in intrinsic membrane properties.
      However, alterations in the inhibitory component of the agonist responses were
      agonist specific, indicating that receptor-linked actions of ethanol were
      involved.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353403
TI  - In vivo modulation of excitatory amino acid receptors: microdialysis studies on N
      methyl-D-aspartate-evoked striatal dopamine release and effects of antagonists.
AB  - Striatal dopamine (DA) release was measured following intrastriatal (i.s.)
      administration of N-methyl-D-aspartate (NMDA) to unanesthetized, freely-moving
      rats. One hour after insertion of a removable microdialysis probe and perfusion
      with normal Ringer's solution, a modified Ringer's solution containing 100 mM
      potassium (high-K+ Ringer's) was used to standardize the preparation. DA release
      following i.s. administration of NMDA (12.5 mM in normal Ringer's) was dose
      dependent. When NMDA (12.5 mM) was administered in high-K+ Ringer's, DA release
      was greatly potentiated. Administration of the competitive NMDA receptor
      antagonist aminophosphonovalerate (APV) in normal Ringer's prior to treatment
      with NMDA in high-K+ Ringer's resulted in a significant reduction of DA release
      compared to control animals. In contrast, administration of APV priot to
      treatment with NMDA in normal Ringer's resulted in a significantly increased
      release of DA compared to controls. Administration of the non-competitive NMDA
      antagonist, dextromethorphan (DXT) prior to treatment with NMDA in normal
      Ringer's or NMDA in high-K+ Ringer's caused significant reductions of DA release
      compared to controls. Intrastriatal DXT also caused dose-dependent inhibition of
      high-K+ Ringer's-induced DA release. Similarly, administration of the non
      specific calcium channel blocker, cadmium, prior to treatment with NMDA resulted
      in a significant decrease when compared to control values. Results of this study
      indicate that dose-dependent NMDA-induced striatal DA release is greatly
      potentiated by potassium suggesting that under physiological conditions in vivo,
      striatal NMDA receptors are mostly inactivated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353404
TI  - Differences in neuronal and glial cell phenotypic expression in neuron-glia
      cocultures: influence of glia-conditioned media and living glial cell substrata.
AB  - Neuron-glia cocultures were prepared using, as a source for glial cells, either
      C6 glia (2B clone) of early (2B23) or late (2B111) passages or advanced passages
      of glial cells derived from primary cultures prepared from aged mouse cerebral
      hemispheres (MACH). Six-day-old chick embryo cerebral hemispheres (E6CH) were the
      source of neuron-enriched cultures. Glutamine synthetase (GS) activity was used
      as a marker for astrocytes and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP)
      activity was used as a marker for oligodendrocytes. GS activity was markedly
      enhanced in cocultures of E6CH neurons and 2B23 glioblastic cells, whereas GS
      activity was reduced in cocultures of E6CH neurons and 2B111 astrocytic glia. In
      contrast, CNP activity was enhanced in cocultures of C6 glial cells with E6CH
      neurons. Glial cells from aged mouse brain did not respond to coculturing with
      E6CH neurons. It appears from these findings that neuronal input enhances the
      differentiation of glioblastic cells to either astrocytic or oligodendrocytic
      expression, whereas it decreases the activity of committed astrocytes. In
      contrast, glial cells from aged mouse brain do not respond to neuronal input.
      Choline acetyltransferase (ChAT) activity, a marker for cholinergic neurons, was
      enhanced only when E6CH cultures were grown in conditioned medium (CM) from 2B23
      glioblastic cells. In contrast, ChAT activity was markedly diminished when E6CH
      neurons were cocultured with MACH glial cells but not when grown in CM from MACH
      glial cells. Thus, humoral factors from immature glial cells appear to enhance
      cholinergic neuronal phenotypic expression whereas cell-cell membrane contacts
      with aged glial cells diminish cholinergic phenotypic expression. The findings
      present supportive evidence that neuron-glia interrelationships are age
      dependent.

PMID- 1353405
TI  - [Schizophrenia and Wilson's disease].
AB  - An 18 year-old male first presented a clinical picture of acute psychosis with
      two recurrences at ages 22 and 23. The diagnosis made at that time was paranoid
      schizophrenia. Twelve years after his first psychiatric hospitalization, it was
      discovered that he was suffering from Wilson's disease. In retrospect, the
      clinical picture was atypical, notably with an important neurologic involvement
      mainly parkinsonism almost uncontrollable and aggravated with neuroleptics. The
      chelating treatment with d-penicillamine resulted in partial improvement of the
      neurological involvement because the extrapyramidal and neurovegetative symptoms
      persisted. The psychiatric symptoms improved with fewer neuroleptics than during
      the 12 previous years. However, neuroleptics had to be continued because of the
      delay in diagnosing the illness, which diminished the efficiency of the single
      chelating treatment. The clinical presentation and therapeutic response of this
      patient strongly suggest a link between the cerebral intoxication by copper and
      the psychiatric symptoms.

PMID- 1353406
TI  - American Cancer Society National Conference on New Oncologic Agents. Dallas,
      Texas, February 6-8, 1991.

PMID- 1353407
TI  - A new chromosomal breakpoint in Ph positive, bcr negative chronic myelogenous
      leukemia. Report of a case.
AB  - We report a new case of Ph positive chronic myeloid leukemia (CML) without the
      classical rearrangement in Mbcr. By Southern blot analysis the molecular
      breakpoint was mapped 3 to 8 kb upstream of Mbcr. This region has not been shown
      to be rearranged in any other described case of CML. We did not detect any
      specific abnormal BCR-ABL transcript even with the use of the very sensitive RNA
      PCR technique.

PMID- 1353408
TI  - Loss of heterozygosity at D3S2 locus of short arm of chromosome 3 in chronic
      myelogenous leukemia.
AB  - Loss of heterozygosity (LOH) on the short arm of chromosome 3 was studied in four
      patients with chronic myelogenous leukemia (CML). The bcr gene rearrangement
      negative spleen cells and a B-cell line were used as normal tissue controls. Five
      probes showing restriction fragment length polymorphisms (RFLP) and a variable
      number of tandem repeats on chromosome 3 were used. DNA patterns in Southern
      blotting were compared between normal cells and leukemic cells. One of the four
      patients had LOH at the D3S2 locus mapped to 3p14.3-3p21.3. The LOH was detected
      in the blastic phase, but not in the chronic phase. This patient showed normal
      chromosomes 3 in the blastic phase. These data suggest the possibility of the
      existence of LOH in CML, occurring as a secondary event in the blastic phase, and
      which might have been induced by submicroscopic deletion or somatic
      recombination.

PMID- 1353409
TI  - Detection of DNA alterations in human bladder tumors by DNA fingerprint analyses.
AB  - DNA fingerprint analyses were used to examine the constitutional and tumor DNA
      from 22 bladder tumor patients. DNA alterations, such as loss of bands, new
      bands, and intensity shifts were observed in 10 of the 22 patients. The most
      frequent DNA alteration, occurring in 80% of the patients, was a complete loss of
      one or several bands. Fingerprint abnormalities were present both in low
      malignant superficial tumors and in high-malignant invasive tumors, but were also
      lacking in the latter group. Apparently no relationship exists between
      fingerprint abnormalities and gross chromosomal aberrations or the proportion of
      S-phase cells as measured by flow cytometry or development of recurrent tumors
      during a limited observation period. Thus, whether fingerprint aberrations
      express genetic alterations directly involved in the malignancy potential of
      bladder carcinoma remains an open question.

PMID- 1353410
TI  - Difference in the response of neu and ras oncogene-induced rat mammary carcinomas
      to early and late ovariectomy.
AB  - Rat mammary carcinomas were induced by directly inserting activated neu or ras
      genes into in situ rat mammary ductal cells using replication-defective
      retroviral vectors. neu was over 200 times more potent than ras in inducing rat
      mammary carcinomas. Ovariectomy 2 days postinfection dramatically reduced the
      occurrence of carcinomas induced by neu and extended their latency. In general,
      early ovariectomy had much less effect on the occurrence of carcinomas induced by
      ras and had no significant effect on their latency. Carcinomas induced by neu in
      ovariectomized rats had down-regulated estrogen receptor and progesterone
      receptor, while those induced by ras had only down-regulated progesterone
      receptor. Fully progressed mammary carcinomas in intact rats induced by both neu
      and ras had a similar response to ovariectomy, with an approximate regression
      rate of 60%. These data suggest that the activation of ras, but not neu, can
      replace at least some functions performed by ovarian hormones in the early phases
      of mammary carcinogenesis. These data also suggest a role for antiestrogen drug
      therapy in the prevention of neu-associated breast cancer.

PMID- 1353411
TI  - Evidence for a tumor suppressor gene on chromosome 19q associated with human
      astrocytomas, oligodendrogliomas, and mixed gliomas.
AB  - Previous studies have shown frequent allelic losses of chromosomes 9p, 10, 17p,
      and 22q in glial tumors. Other researchers have briefly reported that glial
      tumors may also show allelic losses of chromosome 19, suggesting a putative tumor
      suppressor gene locus on this chromosome (D. T. Ransom et al., Proc. Am. Assoc.
      Cancer Res., 32:302, 1991). To evaluate whether loss of chromosome 19 alleles is
      common in glial tumors of different types and grades, we performed Southern blot
      restriction fragment length polymorphism analysis for multiple chromosome 19 loci
      in 122 gliomas from 116 patients. Twenty-nine tumors had loss of constitutional
      heterozygosity of 19q, and four tumors had partial deletions of 19q. Allelic
      losses on 19q were restricted to grade III anaplastic astrocytomas (4/9) and
      grade IV glioblastomas (11/46), grade II oligodendrogliomas (2/5) and grade III
      anaplastic oligodendrogliomas (2/2), and grade II (5/8) and grade III (5/7) mixed
      oligoastrocytomas. These data demonstrate genetic similarities between
      astrocytomas, oligodendrogliomas, and mixed glial tumors and indicate the
      presence of a glial tumor suppressor gene on chromosome 19q.

PMID- 1353412
TI  - Adenovirus E1A targets key regulators of cell proliferation.
AB  - Studies of E1A support the notion that small DNA tumour viruses target cellular
      pathways at key points that are amenable to regulation. In the case of E1A, these
      targets appear to be points of control of cellular proliferation and, in
      particular, proteins that regulate the progression of cells from G0 and G1 phases
      of the cell cycle into the S phase. In several cases, recent studies have
      identified complexes between the viral targets and other cellular proteins. These
      interactions may provide insight not only into the mechanism of E1A mediated
      transformation but also into the control of proliferation in normal cells.

PMID- 1353413
TI  - Functional evidence for human tumour suppressor genes: chromosome and molecular
      genetic studies.
AB  - There is now ample genetic and some functional evidence for the existence of
      tumour suppressor genes. Although much of the functional evidence has been
      derived from somatic cell hybrid and chromosome transfer studies, it is critical
      that cloned candidate tumour suppressor genes be used in such functional assays.
      Our experience with RB and p53 indicates that much will be learned about the
      control of the cell cycle from studies of tumour suppressor genes. However, the
      handful of candidate genes cloned to date also indicates a variety of cellular
      localizations and cellular functions. Thus, just as oncogenes seem to act to
      promote growth at many levels of metabolic control, it would seem that tumour
      suppressor genes act in complementary ways to control cell proliferation. The
      molecular genetic study of cancer has truly entered an exciting phase.

PMID- 1353414
TI  - Cardiovascular mass and ventricular function after celiprolol in Wistar-Kyoto and
      spontaneously hypertensive rats.
AB  - OBJECTIVE: The effects of a new beta 1 adrenergic receptor blocking agent with
      beta 2 receptor agonistic properties on cardiovascular mass, left ventricular
      function, and aortic distensibility were studied in Wistar-Kyoto (WKY) and
      spontaneously hypertensive (SHR) rats. METHODS: 20 male SHR and 20 male WKY rats
      (10 treated and 10 untreated) aged 22 weeks were studied after three weeks of
      treatment. Cardiovascular mass was measured and left ventricular function was
      assessed using electromagnetic flowmetry while rapidly infusing whole blood at
      pharmacologically reduced mean arterial pressure and at pretreatment arterial
      pressure levels. Aortic distensibility was assessed by obtaining pressure-volume
      relationships in isolated aortic segments. RESULTS: Mean arterial pressure was
      reduced without changing cardiac output in SHR (p less than 0.01); it remained
      unchanged in WKY despite reduced cardiac output. Most noteworthy, and like no
      other agent studied to date, celiprolol significantly reduced both left and right
      ventricular as well as aortic mass in both WKY and SHR. Despite these similar
      mass reductions, celiprolol improved left ventricular function (p less than 0.01)
      and aortic distensibility (p less than 0.05) only in the SHR, a function
      maintained even when mean arterial pressure was increased abruptly to
      pretreatment levels. CONCLUSIONS: Unlike other beta receptor blockers (or any
      other agent studied in the SHR), celiprolol was effective in reducing mass of
      right and left ventricles and of aorta; decreasing mean arterial pressure through
      a fall in total peripheral resistance; and improving left ventricular function
      and aortic distensibility in the SHR. In contrast, while these structural changes
      were also produced in WKY, they were not associated with similar functional
      responses. These findings provide further support for the thesis of a structural
      and haemodynamic dissociation in antihypertensive therapy.

PMID- 1353416
TI  - [Subdural empyema. Present possibilities of diagnosis and therapy].
AB  - The authors give an account of their experience with the diagnosis and treatment
      of subdural empyema. In 1953-1991 in the neurosurgical department in Olomouc a
      total of five patients with this diagnosis were treated. None of them died. In
      all patients before operation symptoms of meningeal irritation, fever and in four
      patients a focal neurological symptomatology was observed. The authors reached
      the conclusion that the best surgical approach is craniotomy or craniectomy which
      should be preferred to minor surgical operations. Treatment of the primary
      inflammatory focus leading to the development of subdural empyema must be part of
      the intracranial operation. Regular postoperative follow-up of the patient by
      means of CT makes it possible to detect in time relapses and leads to early
      surgical operation. The authors mention experience focused on possible errors in
      the CT diagnosis. The creation of the picture of subdural collection precedes
      oedema of the hemisphere with a shift of the structures in the median line. The
      subdural collection occurs in the subsequent stage of development of the disease.

PMID- 1353415
TI  - Effects of alpha and beta adrenergic blockade on coronary arterial microvessels
      in the beating canine heart.
AB  - OBJECTIVE: The aim was to clarify the effects of alpha and beta adrenergic
      blockade on coronary arterial microvessels and to assess the role of alpha and
      beta adrenergic tone in normally beating hearts. METHODS: 47 anaesthetised open
      chest dogs were studied. The diameters of epicardial arterial microvessels were
      measured in beating hearts using an incident light fluorescence microscope
      equipped with a floating objective. Drugs were infused into the left anterior
      descending coronary artery keeping the heart rate and aortic pressure at control
      levels. To examine the effect of alpha adrenergic blockade, phentolamine (100
      micrograms.kg-1) was given in the absence or presence of beta adrenergic blockade
      (propranolol 50 micrograms.kg-1). To examine the effect of beta adrenergic
      blockade, propranolol (50 micrograms.kg-1) or three doses of ICI 118,551 (a
      selective beta 2 antagonist, 0.1, 0.5, and 1.0 microgram.kg-1.min-1) was given.
      RESULTS: Coronary arterial microvessels were divided into three groups according
      to the control diameters (D) of small (D less than 100 microns), medium (100 less
      than or equal to D less than 200 microns) and large (D greater than or equal to
      200 microns) groups. In the absence of beta adrenergic blockade, phentolamine
      significantly dilated all vessel groups: small +19.6 (SEM 5.6)%, medium
      +5.8(2.3)%, large +5.3(0.9)%. In the presence of beta adrenergic blockade, the
      vasodilator effect of phentolamine was completely abolished. Propranolol
      constricted all vessel groups: small -3.6(1.1)%, medium -4.8(1.0)%, large 
      3.5(1.0)%. ICI 118,551 significantly constricted the large vessel group [
      2.5(0.6)%] at the mid dose, and the medium and large vessel groups [medium 
      3.1(0.8)%, large -3.5(1.3)%] at the highest dose. CONCLUSIONS: These data
      indicate that (1) the vasodilator effect of phentolamine is induced by beta
      adrenergic stimulation; (2) resting alpha adrenergic tone of coronary arterial
      microvessels is minimal in normally beating hearts, and (3) resting beta
      adrenergic tone may play a physiological role in coronary arterial microvessels,
      and beta 2 adrenergic tone predominates in arterial microvessels greater than 100
      microns in diameter.

PMID- 1353417
TI  - Are the cytosolic components of the nuclear, ER, and mitochondrial import
      apparatus functionally related?

PMID- 1353418
TI  - H-2M3 presents a Listeria monocytogenes peptide to cytotoxic T lymphocytes.
AB  - We report evidence that a major histocompatibility complex-encoded nonclassic
      class I molecule presents a foreign peptide to cytotoxic T lymphocytes (CTL)
      during an infection. Mice immunized with virulent Listeria monocytogenes generate
      CD8+ CTL with alpha beta receptors specific for a bacterial peptide presented by
      a conserved class I molecule encoded in the M region of the major
      histocompatibility complex. The Listeria peptide is digested by carboxypeptidase
      Y but resists aminopeptidase M, and only peptides with N-formyl methionine
      competitively block its presentation to CTL. Transfection with the H-2M3d gene
      enables a negative (H-2w17) cell line to present the bacterial peptide. One
      function, therefore, of H-2M3 is to present bacterial peptides to CTL during
      infection.

PMID- 1353419
TI  - Inhibition of smooth muscle cell proliferation by an antisense
      oligodeoxynucleotide targeting the messenger RNA encoding proliferating cell
      nuclear antigen.
AB  - BACKGROUND: The process by which normally quiescent vascular smooth muscle cells
      (SMCs) change into proliferating cells, which express and respond to multiple
      growth factors, plays a major role in restenosis after coronary angioplasty. We
      are attempting to inhibit SMC proliferation by interventions that inhibit
      specific factors involved in signal transduction pathways leading to cell
      division. To date, all studies taking this approach have attempted to block the
      effects of mitogens acting on the cell surface. In contrast, we have focused on a
      strategy that bypasses cell surface-mediated events by directly inhibiting the
      expression of proliferating cell nuclear antigen (PCNA), an intranuclear protein
      that functions in a final common pathway shared by diverse mitogen-induced
      signals. In the present investigation, we determined whether antisense
      oligodeoxynucleotides (ODNs) complementary to the messenger RNA of PCNA will
      inhibit PCNA expression and thereby reduce SMC proliferation. METHODS AND
      RESULTS: When antisense ODNs (15- or 18-mer), modified to inhibit their
      degradation, are introduced into the medium of rat aortic SMCs in concentrations
      ranging from 10 to 100 microM, the 18-mer ODN, in a concentration-related manner,
      decreases SMC growth (as assessed by cell counting) by more than 50%. This effect
      persists for at least 9 days. An ODN with the same nucleotides but a scrambled
      sequence has little effect. Western blots and immunocytochemistry indicate that
      the antisense ODN reduces expression of PCNA protein. CONCLUSIONS: Our results
      demonstrate that an antisense ODN directed at the messenger RNA of PCNA decreases
      expression of the PCNA gene product and reduces SMC proliferation. In addition,
      these results provide an important impetus to initiating in vivo studies to
      determine the feasibility of antisense strategies in the prevention of coronary
      restenosis.

PMID- 1353420
TI  - Enhancement of the force-frequency effect on myocardial contractility by
      adrenergic stimulation in conscious dogs.
AB  - BACKGROUND: The influence of changes in heart rate on myocardial contractility
      (the force-frequency effect) differs under various experimental conditions,
      including the anesthetized versus the conscious state. METHODS AND RESULTS: To
      assess the influence of beta-adrenergic stimulation on force-frequency effects on
      myocardial contraction and relaxation, seven instrumented conscious dogs were
      studied in which heart rate could be controlled by atrial pacing after the
      intrinsic rate was slowed with a bradycardiac agent (UL-FS 49 0.5-0.75 mg/kg).
      Left ventricular (LV) pressure was measured with a micromanometer under resting
      conditions and during dobutamine infusion at low, intermediate, and high doses
      (2.7, 5.4, and 10.7 micrograms/kg/min). At each dose, heart rate was
      progressively increased from 100 to 210 beats per minute. In the absence of
      dobutamine (control), no significant positive force-frequency effect was detected
      on LV dP/dtmax; this was probably due to the known effect of the observed
      decrease in preload to reduce LV dP/dtmax, thereby offsetting an effect of the
      force-frequency response to increased dP/dt. However, during dobutamine
      infusions, the force-frequency effect was observed to increase significantly in a
      dose-dependent manner with increases in heart rate. An increase in heart rate
      from 100 to 210 beats per minute increased LV dP/dtmax by 12.4 +/- 12.5% with low
      dose, 22.7 +/- 13.1% with intermediate-dose, and 27.5 +/- 8.9% with high-dose
      dobutamine. Changes in preload and aortic pressure were within the same ranges
      under control conditions and at each of the three dobutamine doses. The time
      constant of LV pressure fall (tau) was significantly shorter with increases in
      heart rate during control, but only the highest dobutamine dose caused further
      significant shortening in tau with increased heart rate. CONCLUSIONS: These data
      indicate that there is a pronounced dose-dependent action of beta-adrenergic
      stimulation to enhance force-frequency-induced contractile responses in normal
      conscious dogs.

PMID- 1353421
TI  - Hemodynamic and reflex sympathetic control of transmural activation and rate of
      ventricular tachycardia in ischemic and hypertrophic ventricular myocardium of
      the dog.
AB  - BACKGROUND: A previous study found that the electrophysiological response to
      ischemia is altered in hypertrophic myocardium, resulting in prolonged transmural
      activation time (TAT) associated with induction of sustained monomorphic
      ventricular tachycardia. This study investigated the role of hemodynamics in
      modulating TAT and the cycle length of induced ventricular tachycardia (VT) in
      dogs with left ventricular hypertrophy (LVH). METHODS AND RESULTS: Anesthetized
      open-chest dogs underwent 3 hours of uninterrupted circumflex coronary occlusion.
      During atrial drive, TAT was recorded between endocardial and epicardial bipolar
      pairs on the same multipolar plunge needle placed in nonischemic and ischemic
      zones, documented by triphenyltetrazolium chloride staining. TAT and VT induced
      by up to three extrastimuli were studied during hypertension (control), during
      normotension produced most frequently by nitroprusside infusion (3-6
      micrograms/kg/min), and during further hypertension most frequently produced by
      phenylephrine infusion (1-5 micrograms/kg/min). Twenty-five dogs with chronic
      hypertension and LVH (group 1) produced by a single-kidney renal clamp mechanism
      and 15 control dogs were studied. In the latter, neither intervention altered
      TAT, and no VT was inducible. In group 1, however, nitroprusside reversibly
      prolonged TAT within the ischemic zone (mean +/- SEM, 31 +/- 3 to 34 +/- 3 msec,
      p less than 0.005) and cycle length of induced VT (204 +/- 19 to 240 +/- 17 msec,
      p less than 0.01). Phenylephrine reversibly shortened both TAT in the ischemic
      zone (33 +/- 2 to 28 +/- 2 msec, p less than 0.05) and cycle length of VT (219 +/
      17 to 165 +/- 11 msec, p less than 0.025). Cycle length of VT and TAT were
      dissociated from blood pressure elevation in two dogs with LVH; when blood
      pressure was elevated by sympathetic nerve stimulation, cycle length of VT and
      TAT were prolonged. In 11 dogs with LVH (group 2), prolongation of TAT with
      nitroprusside infusion was prevented by intravenous metoprolol (1.0 mg/kg). Of 12
      dogs with LVH and inducible VT (group 3), seven still had VT inducible after
      metoprolol, but the cycle length of VT was still prolonged with nitroprusside
      infusion. CONCLUSIONS: These results suggest that 1) TAT in acutely ischemic LVH
      was uniquely responsive to hemodynamic influences, an effect prevented by beta
      blockade with metoprolol, and 2) the cycle length of VT was also uniquely
      regulated by hemodynamic influences but not blocked by metoprolol.

PMID- 1353422
TI  - N-methyl-D-aspartate antagonists suppress the development of frog symmetric
      monocular optokynetic nystagmus observed after unilateral visual deprivation.
AB  - In monocular vision, frogs display a unidirectional optokinetic nystagmus (OKN),
      reacting only to temporal-nasal (T-N) stimulation. The OKN N-T component is
      almost absent. However, prolonged monocular visual deprivation by unilateral
      eyelid suture provoked the appearance of the N-T component. The analysis of
      search coil recordings showed that the slow phase velocity gain of both T-N and N
      T components became similar. Chronic administration of N-methyl-D-aspartate
      (NMDA) antagonists for the duration of deprivation prevented the appearance of a
      symmetrical monocular OKN in frogs: following repeated intraperitoneal injections
      of either MK 801, CGS 19755 or intrapretectal microinjections of 2-amino-5
      phosphonovalerate (APV), the N-T component did not appear, and OKN remained
      asymmetrical. Thus NMDA receptors appear to be involved in the control of the
      plasticity process which allows monocular OKN of adult lower vertebrates to
      become symmetrical.

PMID- 1353424
TI  - Scintigraphic study of extra-adrenal ganglioneuroma in a patient with overlap
      between multiple endocrine neoplasia types 1 and 2.
AB  - A 27-year-old woman was diagnosed with a pituitary prolactinoma. Seven years
      later, when she was 34, an abdominal mass was incidentally discovered and
      ascribed to the right adrenal gland on the basis of evidence from
      ultrasonography, computed tomography, and arteriography. Adrenal scintigraphy
      with Se-75 selenomethylcholesterol imaged both adrenal glands, but the right
      gland was distorted, suggesting external compression. I-131 MIBG was not taken up
      by the mass. At surgery, an extra-adrenal ganglioneuroma was found and excised.
      This case represents an overlap between multiple endocrine neoplasia types 1 and
      2. The failure of the ganglioneuroma to concentrate MIBG was likely caused by
      secretory inactivity of a biologically mature tumor.

PMID- 1353423
TI  - Involvement of dipeptidyl peptidase IV in an in vivo immune response.
AB  - Dipeptidyl peptidase IV (DP IV) is a serine protease that selectively cleaves X
      Pro dipeptides from polypeptides and proteins. Among blood cells, this enzyme
      occurs preferentially on the surface of CD4+ T cells and the amount of enzyme
      activity increases with T cell activation. In previous work, two potent and
      specific peptidyl-boronic acid inhibitors of DP IV, Ala-boroPro and Pro-boroPro,
      were synthesized and Pro-boroPro was shown to suppress antigen-specific
      proliferative responses of T cells in vitro. In this study, we tested the in vivo
      effects of these inhibitors. Subcutaneous injection of Ala-boroPro or Pro-boroPro
      into BALB/c mice inhibited DP IV activity in serum and spleen cell suspensions.
      Repeated injections of more than 10 micrograms of Ala-boroPro or Pro-boroPro at
      12 h intervals maintained in vivo DP IV activity at less than 30% of the normal
      level. Repeated injections of the inhibitors during the primary, secondary or
      tertiary immune response to bovine serum albumin (BSA) reduced anti-BSA antibody
      production. Without inhibitor, immunization with BSA was followed by a temporary
      decrease in serum DP IV activity and then by enhanced serum enzyme activity after
      several days. These results provide the first direct evidence that DP IV plays an
      important role in immune response in vivo.

PMID- 1353426
TI  - Hematopoietic stem cells. Animal models and human transplantation. Introduction.

PMID- 1353425
TI  - [Effects of beta blocking agent iontophoresis by modulated sinusoidal current].
AB  - The action of the transcutaneous application of propranolol using modulated
      sinusoidal current iontophoresis was studied. When this way of administration is
      used, the drug, while maintaining its negative chronotropic effect, loses the
      negative inotropic one. Investigations were performed on 58 men aged 32 to 62 who
      underwent an aortocoronary bypass for myocardial ischemia. Thirty-four patients
      had already had myocardial infarction. The drug reduced the heart rate and
      increased cardiac contractility. Moreover, the study showed that only the
      levogyral isomer of propranolol (the only active one) passes through the skin.

PMID- 1353427
TI  - Hematopoietic stem cells. Animal models and human transplantation.

PMID- 1353428
TI  - The fetal liver as a source of stem cells for transplantation into fetuses in
      utero.

PMID- 1353429
TI  - Human umbilical cord blood as a source of transplantable hematopoietic stem and
      progenitor cells.

PMID- 1353430
TI  - Biology and clinical application of peripheral blood stem cells.

PMID- 1353431
TI  - Gene transfer into hematopoietic stem cells: prospects for human gene therapy.

PMID- 1353432
TI  - Gene transfer into hematopoietic stem cells.

PMID- 1353433
TI  - Clonal analysis of hematopoietic stem cell development in vivo.

PMID- 1353434
TI  - What we have learned from retroviral marking of hematopoietic stem cells.

PMID- 1353435
TI  - Status of high proliferative potential colony-forming cells in the hematopoietic
      stem cell hierarchy.

PMID- 1353436
TI  - Characterization of several classes of mouse hematopoietic progenitor cells.

PMID- 1353437
TI  - Symposium on Cocaine: Scientific and Social Dimensions. London, 20-22 July 1991.

PMID- 1353438
TI  - The prion protein gene: a role in mouse embryogenesis?
AB  - The neural membrane glycoprotein PrP (prion protein) has a key role in the
      development of scrapie and related neurodegenerative diseases. During
      pathogenesis, PrP accumulates in and around cells of the brain from which it can
      be isolated in a disease-specific, protease-resistant form. Although the
      involvement of PrP in the pathology of these diseases has long been known, the
      normal function of PrP remains unknown. Previous studies have shown that the PrP
      gene is expressed tissue specifically in adult animals, the highest levels in the
      brain, with intermediate levels in heart and lung and low levels in spleen.
      Prenatally, PrP mRNA has been detected in the brain of rat and hamster just prior
      to birth. In this study we have examined the expression of the PrP gene during
      mouse embryonic development by in situ hybridisation and observed dramatic
      regional and temporal gene expression in the embryo. Transcripts were detected in
      developing brain and spinal cord by 13.5 days. In addition, PrP gene expression
      was detected in the peripheral nervous system, in ganglia and nerve trunks of the
      sympathetic nervous system and neural cell populations of sensory organs.
      Expression of the PrP gene was not limited to neuronal cells, but was also
      detected in specific non-neuronal cell populations of the 13.5 and 16.5 day
      embryos and in extra-embryonic tissues from 6.5 days. This cell-specific
      expression suggests a pleiotropic role for PrP during development.

PMID- 1353439
TI  - Engrailed expression in the anterior lineage compartment of the developing wing
      blade of Drosophila.
AB  - The developing wing of Drosophila melanogaster was examined at larval and pupal
      stages of development to determine whether the anterior-posterior lineage
      boundary, as identified by lineage restrictions, was congruent with the
      boundaries defined by the expression of posterior-specific (engrailed, invected),
      and anterior-specific (cubitus interruptus-D) genes. The lineage boundary was
      identified by marking mitotic recombinant clones, using an enhancer trap line
      with ubiquitous beta-gal expression in imaginal tissues; clones of +/+ cells were
      identified by their lack of beta-gal expression. Domains of gene expression were
      localized using antibodies and gene specific lacZ constructs. Surprisingly, it
      was found that engrailed expression extended a small distance into the anterior
      lineage compartment of the wing blade, as identified with anti-en/inv mAb, anti
      en polyclonal antiserum, or an en-promoter-lacZ insert, ryxho25. This anterior
      expression was not present in early third instar discs, but appeared during
      subsequent larval and pupal development. In contrast, the expression of cubitus
      interruptus-D, as identified using the ci-Dplac insert, appeared to be limited to
      the anterior lineage compartment. Thus, en expression is not limited to cells
      from the posterior lineage compartment, and en and ci-D activities can overlap in
      a region just anterior to the lineage compartment boundary in the developing
      wing. The lineage boundary could also be identified by a line of aligned cells in
      the prospective wing blade region of wandering third instar discs. A
      decapentaplegic-lacZ construct was expressed in a stripe several cells anterior
      to the lineage boundary, and did not define or overlap into the posterior lineage
      compartment.

PMID- 1353440
TI  - Homeotic genes have specific functional roles in the establishment of the
      Drosophila embryonic peripheral nervous system.
AB  - The Drosophila embryonic peripheral nervous system (PNS) contains segment
      specific spatial patterns of sensory organs which derive from the ectoderm. Many
      studies have established that the homeotic genes of Drosophila control segment
      specific characteristics of the epidermis, and more recently these genes have
      also been shown to control gut morphogenesis through their expression in the
      visceral mesoderm (Tremml, G. and Bienz, M. (1989), EMBO J. 8, 2677-2685). We
      report here the roles of homeotic genes in establishing the spatial patterns of
      sensory organs in the embryonic PNS. The PNS was examined in embryos homozygous
      for mutations in the homeotic genes Sex combs reduced (Scr), Antennapedia (Antp),
      Ultrabithorax (Ubx), abdominal-A (abd-A) and Abdominal-B (Abd-B) with antibodies
      that label specific subsets of sensory organs. Our results suggest that the
      homeotic genes have specific roles in establishing the correct spatial patterns
      of sensory organs in their normal domains of expression. In addition, we also
      report the effects of ectopic expression of the homeotic genes labial (lab),
      Deformed (Dfd), Scr, Antp or Ubx on the normal development of sensory organs in
      the embryonic PNS. Interestingly, while previous studies have concluded that
      ectopic expression of the homeotic genes Dfd, Scr and Antp has no effect on the
      segmental identity of the abdominal segments, our results demonstrate that this
      is not true. We show that ectopic expression of these genes does result in the
      disruption of the developing PNS in the abdomen. Our results are suggestive of a
      role for the homeotic gene products in regulating genes which are necessary for
      generating sensory progenitor cells in the developing PNS.

PMID- 1353441
TI  - Transplantation of encapsulated canine islets into spontaneously diabetic BB/Wor
      rats without immunosuppression.
AB  - Extended survival of canine islet xenografts implanted in spontaneously diabetic
      BB/Wor rats has been achieved by islet encapsulation inside cylindrical chambers
      fabricated from permselective acrylic membranes. Intraperitoneal implantation of
      the encapsulated islets reversed the diabetic state of the 10 recipients within
      24 h. Plasma glucose levels declined from a preimplantation level of 459 +/- 30
      to 102 +/- 14 mg/dl during the first 10 days. All of the animals sustained these
      levels for at least 1 month, and 2 animals for at least 2 and 8 months,
      respectively. To confirm that glucose homeostasis resulted from the encapsulated
      islet grafts, the implants were removed from 2 rats 1 month postimplantation,
      whereas a third was removed at 2 months. Hyperglycemia was observed immediately
      in all 3 animals, with glucose levels rising from 100 +/- 3 to 510 +/- 43 mg/dl
      within 1 day. In contrast, diabetic control rats (n = 4) receiving
      nonencapsulated islets became hyperglycemic in less than 1 week. The iv glucose
      tolerance test K value (decline in glucose levels, percent per min) at 10 days
      was 2.3 +/- 0.4 compared with 0.6 +/- 0.1 (P less than 0.005) and 3.1 +/- 0.1 (P
      less than 0.02) for untreated diabetic (n = 4) and normal control (n = 4) groups.
      Histological analyses and electron microscopy of long term functioning grafts
      revealed well preserved islets, with hormone-producing alpha-, beta-, and delta
      cells; the membranes were generally free of fibrosis and host cell adherence.
      These results demonstrate that permselective artificial membranes can protect
      discordant islet xenografts from both graft rejection and autoimmune destruction
      for more than 1 month in an animal model that is similar in several respects to
      human type I diabetes.

PMID- 1353442
TI  - Estradiol selectively regulates agonist binding sites on the N-methyl-D-aspartate
      receptor complex in the CA1 region of the hippocampus.
AB  - Estradiol alters cognitive function and lowers the threshold for seizures in
      women and laboratory animals. Both of these activities are modulated by the
      excitatory neurotransmitter glutamate in the hippocampus. To assess the
      hypothesis that estradiol increases the sensitivity of the hippocampus to
      glutamate activation by increasing glutamate binding sites, the densities of N
      methyl-D-aspartate (NMDA) agonist sites (determined by NMDA displaced glutamate),
      competitive antagonist sites (CGP 39653), noncompetitive antagonist sites (MK801)
      as well as the non-NMDA glutamate receptors for kainate and AMPA (using kainate
      and CNQX, respectively) were measured using autoradiographic procedures. Two days
      of estradiol treatment increased the density of NMDA agonist, but not of
      competitive nor noncompetitive NMDA antagonist binding sites exclusively in the
      CA1 region of the hippocampus. The density of noncompetitive NMDA antagonist
      sites, however, was decreased in the dentate gyrus by estradiol treatment.
      Ovarian steroids had no effect on the density of kainate or AMPA receptors in any
      region of the hippocampus examined. These data indicate that the agonist and
      antagonist binding sites on the NMDA receptor/ion channel complex are regulated
      independently by an as yet unidentified mechanism, and that this regulation
      exhibits regional specificity in the hippocampus. The increase in NMDA agonist
      sites with ovarian hormone treatment should result in an increase in the
      sensitivity of the hippocampus to glutamate activation which may mediate some of
      the effects of estradiol on learning and epileptic seizure activity.

PMID- 1353443
TI  - PC12 rat pheochromocytoma cells synthesize dynorphin. Its secretion is modulated
      by nicotine and nerve growth factor.
AB  - The PC12 is a cloned rat pheochromocytoma cell line that retains a number of
      chromaffin cell characteristics, such as the presence of nicotinic cholinergic
      receptors, the synthesis and secretion of catecholamines, and the expression of a
      number of neuropeptide genes. The PC12 cell line is a useful model for the study
      of neuronal development, since PC12 cells can be induced to differentiate toward
      sympathetic neurons after exposure to nerve growth factor (NGF). PC12 cells can
      also be induced to differentiate toward the opposite direction, i.e. toward
      mature chromaffin cells. Morphological and biochemical changes mark the
      differentiation of PC12 cells toward either direction. Among the substances
      proposed as biochemical markers of PC12 cell differentiation toward chromaffin
      cells is the endogenous opioid precursor proenkephalin and its posttranslational
      peptide products. Indeed, the proenkephalin gene is expressed in both adrenal
      chromaffin and PC12 cells. The secretion of enkephalins from PC12 cells increases
      by several-fold after differentiation toward chromaffin cells. On the other hand,
      prodynorphin (another endogenous opioid precursor) is not present in normal
      adrenal chromaffin cells, but it is synthesized by human pheochromocytomas. It,
      thus, appears that dedifferentiation of chromaffin cells induces expression of
      the prodynorphin gene. Consequently, the aim of this study was to determine
      whether the rat pheochromocytoma-derived PC12 cell line expresses the
      prodynorphin gene, if it secretes dynorphins, and if the NGF-induced
      differentiation of PC12 cells toward sympathetic neurons affects the secretion of
      the latter. We found the following. 1) PC12 cells synthesize prodynorphin and
      secrete its peptide products. 2) The size of the prodynorphin transcript and the
      mol wt of its dominant form of dynorphin appear to be similar or identical to
      those of prodynorphin in rat anterior pituitary. 3) PC12 dynorphin secretion is
      increased, in a dose-dependent manner, after nicotinic cholinergic stimulation,
      an effect blocked by the specific nicotine antagonist hexamethonium. Thus, it
      appears that after cholinergic stimulation, PC12 dynorphin is cosecreted with
      catecholamines, a phenomenon described for a number of neuropeptides, including
      the proenkephalin-derived opioids. 4) The NGF-mediated differentiation of PC12
      cells into sympathetic neurons exerted a stimulatory effect on basal, nicotine
      induced, and depolarization-dependent dynorphin secretion. However, NGF did not
      shift the nicotine dose-response curve of dynorphin secretion. In conclusion, it
      appears that while changes in the secretion of proenkephalin-derived peptides may
      serve as a marker of PC12 cell differentiation toward chromaffin cells, an
      increase in the secretion of prodynorphin-derived peptides may represent a marker
      of NGF-induced differentiation of PC12 cells toward sympathetic neurons.

PMID- 1353444
TI  - Growth hormone receptor messenger ribonucleic acid distribution in the adult male
      rat brain and its colocalization in hypothalamic somatostatin neurons.
AB  - The activity of both somatostatin (SS) and GH-releasing hormone (GHRH) neurons
      within several hypothalamic nuclei is regulated, in part, by the feedback effects
      of GH. However, whether GH, or its intermediate, insulin-like growth factor I,
      acts on these neurons to alter the synthesis and release of SS and GHRH is
      unknown. We argued that if GH itself acts directly on the brain to govern its own
      secretion, then regions of the brain containing SS and GHRH neurons may express
      the GH receptor gene. We tested this hypothesis by performing in situ
      hybridization for GH receptor messenger RNA (mRNA) and mapping its distribution
      in the brain. We observed GH receptor mRNA-containing cells in various brain
      regions including the thalamus, septal region, hippocampus, dentate gyrus,
      amygdala, and hypothalamus. Next we sought evidence for expression of the GH
      receptor mRNA by SS neurons in the hypothalamus. We addressed this by performing
      a double-label in situ hybridization to identify neurons expressing both SS mRNA
      and GH receptor mRNA. We report that SS neurons in the periventricular nucleus
      and in the paraventricular nucleus coexpress the GH receptor gene, whereas few,
      if any, of the SS neurons in the cortex express detectable amounts of the GH
      receptor mRNA. These findings suggest that GH acts directly on the brain and
      participates in the regulation of its own secretion through a direct action on
      hypothalamic SS neurons.

PMID- 1353445
TI  - Polycomb and polyhomeotic are constituents of a multimeric protein complex in
      chromatin of Drosophila melanogaster.
AB  - The polycomb group (Pc-G) genes are responsible for maintaining the repressed
      state of homeotic genes during development. It has been suggested that the Pc-G
      exerts its transcriptional control by regulating higher order chromatin
      structure. In particular, the finding of genetic and molecular similarities to
      components involved in heterochromatin formation, led to the proposal that
      homeotic genes are permanently repressed by mechanisms similar to those
      responsible for heterochromatin compaction. Because of synergistic effects, Pc-G
      gene products are thought to act in a multimeric complex. Using
      immunoprecipitation we show that two members of the Pc-G, Polycomb and
      polyhomeotic, are constituents of a soluble multimeric protein complex. Size
      fractionation indicates that a large portion of the two proteins are found in a
      distinct complex of molecular weight 2-5 x 10(6) Da. During embryogenesis the two
      proteins show the same spatial distribution. In addition, by double
      immunofluorescence labelling we can demonstrate that Polycomb and polyhomeotic
      have exactly the same binding patterns on polytene chromosomes of larval salivary
      glands. We propose that some Pc-G proteins act in multimeric complexes to compact
      the chromatin of stably repressed genes like the homeotic regulators.

PMID- 1353446
TI  - Selection for high-level chloroquine resistance results in deamplification of the
      pfmdr1 gene and increased sensitivity to mefloquine in Plasmodium falciparum.
AB  - A chloroquine resistant cloned isolate of Plasmodium falciparum, FAC8, which
      carries an amplification in the pfmdr1 gene was selected for high-level
      chloroquine resistance, resulting in a cell line resistant to a 10-fold higher
      concentration of chloroquine. These cells were found to have lost the
      amplification in pfmdr1 and to no longer over-produce the protein product termed
      P-glycoprotein homologue 1 (Pgh1). The pfmdr1 gene from this highly resistant
      cell line was not found to encode any amino acid changes that would account for
      increased resistance. Verapamil, which reverses chloroquine resistance in FAC8,
      also reversed high-level chloroquine resistance. Furthermore, verapamil caused a
      biphasic reversal of chloroquine resistance as the high-level resistance was very
      sensitive to low amounts of verapamil. These data suggest that over-expression of
      the P-glycoprotein homologue is incompatible with high levels of chloroquine
      resistance. In order to show that these results were applicable to other
      chloroquine selected lines, two additional mutants were selected for resistance
      to high levels of chloroquine. In both cases they were found to deamplify pfmdr1.
      Interestingly, while the level of chloroquine resistance of these mutants
      increased, they became more sensitive to mefloquine. This suggests a linkage
      between the copy number of the pfmdr1 gene and the level of chloroquine and
      mefloquine resistance.

PMID- 1353448
TI  - Presentation of superantigen by human T cell clones: a model of T-T cell
      interaction.
AB  - Superantigens (SAg) interact with T lymphocytes bearing particular V beta
      sequences as part of their T cell receptor (TcR). The interaction, however,
      requires the presence of major histocompatibility complex (MHC) class II
      molecules on antigen-presenting cell (APC). In peculiar circumstances, MHC class
      II+ T cell clones (TCC) have been shown to present peptides and selected antigens
      interacting with antigen-specific TCC in the absence of APC. In this report we
      studied the capacity of SAg to mediate a T-T cell interaction, investigating the
      TCC ability to present a panel of staphylococcal enteroxins (SE) independently of
      the presence of added APC. Upon exposure to a broad range of SE concentrations,
      MHC class II+ TCC showed an intense proliferative response even in the absence of
      professional APC. Diverse SE optimally stimulated responder TCC at different
      concentrations. The proliferation was inhibited by anti-DR monoclonal antibodies,
      both in the presence and in the absence of APC. The SE activation of TCC in the
      absence of APC induced the same series of phenotypic variations as that observed
      following the TCC stimulation with APC. Irradiated TCC efficiently presented
      membrane-bound SE to responder TCC as well as professional APC. These results
      show that a single cell of a given clone effectively presents the SE to other
      cells of the same clone, and provide evidence that SAg can efficiently mediate T
      T cell interaction. In addition, the possibility also exists that one cell of the
      clone can actually undergo an auto-stimulation via SAg-mediated interactions
      between its own TcR and MHC class II molecule. It has recently been suggested
      that the V beta-selective depletion of T cells observed in acquired
      immunodeficiency syndrome (AIDS) patients might be a consequence of the
      interaction between a human immunodeficiency virus (HIV)-encoded SAg and T cells
      expressing a SAg complementary V beta. We suggest that the hypothesized HIV
      encoded SAg might mediate T-T cell interactions that could play a relevant role
      in the V beta-selective depletion of T lymphocytes observed in HIV-infected
      patients.

PMID- 1353449
TI  - Synthesis and characterization of biotinylated and photoactivatable neuroleptics.
      Novel bifunctional probes for dopamine receptors.
AB  - We have synthesized and characterized a series of novel derivatives of
      established antagonists of the neurotransmitter dopamine, i.e. butyrophenones,
      hexahydrocarbolines and phenothiazines. All derivatives were biotinylated, some
      of them carried an additional (photoactivatable) azido group. In the case of
      butyrophenones, the structural modifications were introduced at the aliphatic
      keto group and/or the heterocyclic ring system, both modifications resulting in
      significant decreases in binding affinity to dopamine D2 and dopamine D1 receptor
      subtypes. Biotinylation of hexahydrocarbolines significantly increased their
      binding affinity to D1 receptors, with the affinity for D2 receptors increasing
      only slightly, or remaining approximately the same, as compared to the parent
      compound. As a consequence, the derivatized hexahydrocarbolines behaved as
      nonselective antagonists of dopamine. Biotinylation of phenothiazines increased
      their binding affinity to both main subtypes of dopamine receptors by at least
      one order of magnitude, resulting in binding affinities in the nM range. These
      derivatives bound to both D1 and D2 receptor subtypes. In three of the
      biotinylated derivatives the photoactivatable azido group was introduced. These
      compounds bound to synaptosomal membranes from bovine caudate nuclei with similar
      affinity and subtype specificity as the biotinylated derivatives, and
      photoaffinity labelling was shown to proceed under mild conditions and
      selectively. These novel bifunctional ligands may become useful tools in the
      purification and characterization of dopamine receptors including their
      visualization and localization in the central nervous system and in tissue
      culture.

PMID- 1353447
TI  - Alternative polyadenylation of the amyloid protein precursor mRNA regulates
      translation.
AB  - The sequence of several cDNAs encoding the amyloid protein precursor showed that
      two polyadenylation sites of the mRNA are utilized; RNA blot analysis with
      different riboprobes indicated that this explains the difference between the two
      major 3.2 and 3.4 kb mRNAs found in the human brain. These two mRNAs, which
      contain the whole sequence of the natural molecules, were synthesized by in vitro
      transcription and translated in Xenopus oocytes. The long mRNA using the second
      polyadenylation site produced more protein than the short mRNA. The sequence
      contained within the two polyadenylation sites used in the 3' untranslated region
      of the amyloid protein precursor mRNA was also able to increase the production of
      the chicken lysozyme or the chloramphenicol acetyl transferase, as demonstrated
      by in vivo translation of different chimeric mRNAs obtained by in vitro
      transcription. This difference in protein production was also observed when
      chimeric cDNA constructs were transfected into Chinese hamster ovary cells. Since
      long mRNAs are not more stable than short mRNAs, the sequence contained within
      the two polyadenylation sites of the amyloid protein precursor mRNA increases the
      translation.

PMID- 1353450
TI  - Alpha 1-adrenoceptors in parotid cells: age does not alter the ratio of alpha 1A
      and alpha 1B subtypes.
AB  - Epinephrine stimulation of 45Ca2+ efflux and inositol 1,4,5-trisphosphate
      ((1,4,5)IP3) production in parotid cell aggregates from mature rats was greatly
      inhibited (approximately 70%) by WB 4101 and 5-methylurapidil as compared to a
      small decrease by chloroethylclonidine (approximately 30%). The combination of WB
      4101 or 5-methylurapidil and chloroethylclonidine completely blocked the action
      of epinephrine. The same relative inhibition was observed with senescent animals.
      The results suggest (1) that rat parotids contain both alpha 1-adrenoceptor
      subtypes, i.e., alpha 1A and alpha 1B, in an approximate functional ratio of
      70:30, (2) that this relative ratio is not altered during aging, and (3) that
      both receptors partially mediate 45Ca2+ efflux and (1,4,5)IP3 production in this
      system.

PMID- 1353452
TI  - Subchronic treatment of rats with remoxipride fails to modify sigma binding sites
      in the brain.
AB  - The effects of 14 days' treatment of rats with haloperidol, remoxipride or both
      combined on the sigma binding sites in whole brain and liver were determined. The
      compounds were given subcutaneously via osmotic minipumps at a dose of 0.25
      mg/rat/day (corresponding to about 1 mg/kg body weight/day at start) for
      haloperidol and 2.5 mg/rat/day (10 mg/kg/day) for remoxipride hydrochloride. The
      sigma recognition sites were determined after a washout period of 2 days with the
      radioligand [3H](+)-N-propyl-3-(3-hydroxyphenyl)piperidine ([3H](+)-3-PPP). It
      was found that the haloperidol treatment but not the remoxipride treatment
      decreased the density of the sigma sites in the brain, without any effect on the
      affinities of the ligands. Haloperidol had no effect on the binding of [3H](+)-3
      PPP to the sigma recognition sites in the liver.

PMID- 1353451
TI  - Subtypes of alpha 1-adrenoceptors in DDT1 MF-2 and BC3H-1 clonal cell lines.
AB  - We examined which subtype(s) of alpha 1-adrenoceptors are expressed in the widely
      used DDT1 MF-2 and BC3H-1 cell lines. Pretreatment with chloroethylclonidine
      (CEC) inactivated 76-85% of the specific [125I]BE 2254 binding sites in membrane
      preparations from both cell lines. Competition with subtype-selective competitive
      antagonists showed primarily the alpha 1B subtype in both cell lines. However, in
      BC3H-1 cells 5-methyl-urapidil showed complex behavior suggesting that about half
      of the binding sites had a lower affinity. Chloroethylclonidine pretreatment
      eliminated [3H]inositol phosphate responses to norepinephrine in both cell lines.
      Measurement of intracellular Ca2+ with fura-2 in DDT1 MF-2 cells showed that
      norepinephrine induced a complex response involving both transient and sustained
      components. Chloroethylclonidine pretreatment blocked both responses, while
      chelation of extracellular Ca2+ left the transient response intact but eliminated
      the sustained component. These results support previous work that these cell
      lines contain alpha 1B-adrenoceptors linked to inositol phosphate formation and
      mobilization of intracellular Ca2+. However, these results show that alpha 1B
      adrenoceptors can be linked to Ca2+ influx as well as intracellular mobilization,
      and support the existence of pharmacologically distinct alpha 1B variants.

PMID- 1353453
TI  - Bilateral distribution of aminopeptidase activities in selected structures of a
      photoneuroendocrine circuit and other rat brain areas.
AB  - Provided that soluble aminopeptidases, the most abundant proteolytic enzymes
      found in brain, are involved in the metabolism of several neuropeptides, their
      activity could be a reflect of neuropeptide function. Therefore, in order to
      analyze their rate of participation, we have measured 4 soluble aminopeptidase
      activities: leucine aminopeptidase, arginine aminopeptidase, aspartate
      aminopeptidase, and pyroglutamate aminopeptidase, using arylamide derivatives as
      substrates, in selected structures integrating the photoneuroendocrine circuit
      related to the melatonin rhythm generating system and other rat brain areas. The
      regional distribution of all the activities was heterogenous: a 3-fold (leucine-,
      arginine- and aspartate-aminopeptidase) and 5-fold (pyroglutamate aminopeptidase)
      difference was observed between the regions with the highest and lowest activity.
      Significant differences were displayed between the left and right retina for
      pyroglutamate aminopeptidase and arginine aminopeptidase activities. High levels
      of pyroglutamate aminopeptidase were evident in the retina and adenohypophysis,
      which is consistent with a role for thyrotropin releasing hormone in
      photoreceptive mechanisms, and support its well established role in controlling
      thyrotropin releasing hormone in anterior pituitary. The presence of a high
      activity rate of aspartate aminopeptidase in adenohypophysis implies an active
      participation of angiotensin peptides at this level.

PMID- 1353454
TI  - Inhibitory effect of somatostatin on abnormal GH response to TRH in primary
      hypothyroidism.
AB  - Thyrotropin releasing hormone (TRH) does not promote GH secretion in normal
      subjects but it stimulates GH in a proportion of hypothyroid patients. In this
      study the response of GH to thyrotropin releasing hormone (TRH) was evaluated in
      21 patients with primary hypothyroidism of different origin: 12 with autoimmune
      thyroiditis, 3 idiopathic, 3 congenital, 3 iatrogenic. 11 of these patients had
      never been treated, the others were tested after a drug-free period of at least
      two weeks. Basal plasma concentration of GH was normal in all patients; after TRH
      administration, a significant increase in plasma GH was observed in 4 patients.
      In these responsive patients, somatostatin infusion inhibited the abnormal GH
      response to TRH. It is suggested that the abnormal GH response to TRH in primary
      hypothyroidism might be caused by a relative deficiency of somatostatinergic
      control, which is corrected by exogenous somatostatin administration.

PMID- 1353455
TI  - Cycloheximide can rescue heat-shocked L cells from death by blocking stress
      induced apoptosis.
AB  - Cultured mouse L cells undergo apoptosis upon 1 h heat shock at 43 and 45 degrees
      C. Morphologically characteristic apoptotic cells begin to appear soon after the
      shock. Immunohistochemistry with anti-transglutaminase antibody shows that in
      most treated cells the enzyme is induced. Its activation results in the formation
      of highly cross-linked detergent-resistant apoptotic bodies during recovery.
      Cycloheximide added during hyperthermic stress inhibits the appearance of
      apoptotic bodies, showing that heat-shock-induced apoptosis is dependent on
      protein neosynthesis. The analysis of colony-forming ability of heat-shocked L
      cells shows a survival of 5% at 43 degrees C and less than 0.02% at 45 degrees C.
      When protein synthesis is inhibited during heat shock the fraction of surviving
      cells increases to 23% at 43 degrees C and 0.9% at 45 degrees C. This suggest
      that part of the cells that die upon heat shock are not heavily damaged and would
      have survived in the presence of a block in protein synthesis.

PMID- 1353456
TI  - Structure and identity of a late-replicating and transcriptionally active gene.
AB  - Eukaryotic genes are usually replicated early during S-phase in the cell lineages
      in which they are expressed. Using partially characterized cDNA probes, we
      recently established two exceptions to this rule in the slime mold Physarum
      polycephalum. In this paper, we analyzed the structure and the identity of one of
      these two genes. By genomic cloning and Southern analysis we demonstrate that it
      is a single-copy gene and decipher the structure of the two alleles by taking
      advantage of a restriction fragment length polymorphism. By cDNA cloning and
      sequencing, we deduced the amino acid coding capacity of the mRNA. Finally, we
      confirmed the late replication of this abundantly expressed gene by "gene dosage"
      analysis, an experiment that did not require any drug treatment of the cell. Our
      results provide for the characterization and the structure of the first
      developmentally regulated gene known to be replicated late in S-phase and
      abundantly expressed within a eukaryotic cell.

PMID- 1353457
TI  - Effects of glucagon and an analogue of cAMP on tyrosine aminotransferase in
      isolated chick embryo hepatocytes.
AB  - Hepatocytes were isolated from 17-day-old chick embryos by the use of
      collagenase. Glucagon and dibutyryl cAMP (bt2cAMP), individually or in
      combination, stimulated tyrosine aminotransferase (TAT) activity and synthesis in
      the isolated hepatocytes; maximal stimulation occurred 4 h after exposure of
      hepatocytes to the inducers. The stimulatory effects produced by glucagon and
      bt2cAMP were abolished by treatment of hepatocytes with cordycepin or
      cycloheximide. The effects of the hormone and the cyclic nucleotide were not
      additive. The induction of the enzyme by glucagon suggests a physiological role
      for the hormone in the expression of TAT activity during chick embryonic
      development.

PMID- 1353458
TI  - Two types of proliferating cell nuclear antigen (PCNA) complex formation in
      quiescent normal and xeroderma pigmentosum group A fibroblasts following
      ultraviolet light (uv) irradiation.
AB  - We examined the relationship between the formation of proliferating cell nuclear
      antigen (PCNA) complex with DNA and nucleotide excision repair in human
      fibroblasts following ultraviolet light (uv) irradiation. PCNA complex formation
      was detected by the immunofluorescence method after methanol fixation and
      nucleotide excision repair activity was detected as the unscheduled DNA synthesis
      (UDS) by autoradiography labeled with [3H]thymidine. Quiescent normal cells
      showed a strong punctuated pattern of PCNA staining 5 min to 3 h and UDS 3 h
      after 10 J/m2 of uv irradiation, but they no longer showed PCNA staining and UDS
      24 h after irradiation. In contrast, xeroderma pigmentosum group A (XP-A) cells,
      which lack UDS activity, did not show PCNA staining up to 30 min after
      irradiation; however, unexpectedly, they were stained 3 h and even 24 h after
      irradiation with their staining pattern being different from that in normal
      cells. Namely, the fluorescence spots in XP-A cells were larger in size and much
      smaller in number than those in normal cells. When XP-A cells were fused with
      normal cells with polyethylene glycol treatment, nuclei of XP-A cells showed a
      PCNA staining pattern similar to that of normal cells at 30 min, which was no
      longer detected 24 h after irradiation. These results suggest that there exist
      two types of PCNA complex formation, nucleotide excision repair-related and 
      unrelated, in human fibroblasts following uv irradiation.

PMID- 1353459
TI  - Theileria parva: CD4+ helper and cytotoxic T-cell clones react with a schizont
      derived antigen associated with the surface of Theileria parva-infected
      lymphocytes.
AB  - Theileria parva is a protozoan parasite which infects and transforms bovine
      lymphocytes, resulting in a fatal lymphoproliferative disease. There is evidence
      that immunity to the intralymphocytic schizont stage is mediated by T cells. We
      have previously reported derivation of CD4+ T-cell clones which recognize
      parasite-derived antigens presented on the surface of infected cells in
      conjunction with MHC molecules and partial characterization of the antigens. The
      present study further evaluated one of these antigens, demonstrating that it
      could be derived from cells infected with different parasite stocks as well as
      from purified theilerial schizonts and that it was recognized by primed, but not
      unprimed, bovine lymphocytes including cytolytic CD4+ T cells. Using a cloned
      CD4+ cytolytic cell line, lysis of schizont-infected cells was shown to be MHC
      restricted but not parasite-strain restricted. In addition we demonstrated that T
      cells which respond to the HSS antigen preparation were generated in cattle
      immunized with parasites from any of the three subspecies of T. parva. The
      antigenic material was fractionated by sequential subjection to anion-exchange
      chromatography, hydroxylapatite chromatography, and gel filtration using HPLC,
      which resulted in recovery of approximately 20% of the antigenic material with
      more than 10(6)-fold purification in selected fractions. To assess the molecular
      size of the proteins in the highly purified antigenic fractions, the T. parva
      infected lymphocytes were metabolically labeled before fractionation with 3H
      amino acids and the material was analyzed by SDS-polyacrylamide gel
      electrophoresis and liquid scintillation counting of gel slices. The major
      protein in these fractions had a molecular mass of 9-10 kDa.

PMID- 1353461
TI  - NO., CO and .OH. Endogenous soluble guanylyl cyclase-activating factors.
AB  - Several low molecular weight compounds are capable of activating soluble guanylyl
      cyclase. Recent evidence suggests that some of these are formed under
      physiological conditions: the nitric oxide radical, carbon monoxide and the
      hydroxyl radical. Thus, multiple signal transduction pathways appear to exist
      that form a family of guanylyl cyclase activating factors and thereby regulate
      the intracellular cyclic guanosine 3',5'-monophosphate level.

PMID- 1353460
TI  - A farnesyl arabinoside as an enhancer of glucose transport in rat adipocytes from
      a soft coral, Sinularia sp.
AB  - Separation of a lipophilic extract of a soft coral, Sinularia sp., assayed by
      enhancement of glucose transport in rat adipocytes, gave farnesyl 4-O-beta-D
      arabinopyranosyl-beta-D-arabinopyranoside-2,2',3- triacetate (1a) whose structure
      was determined by spectroscopy. Enhancers of glucose transport may be useful for
      the prevention and treatment of diabetic disorders.

PMID- 1353462
TI  - Neurotransmitter transporters. A novel family of integral plasma membrane
      proteins.
AB  - The re-uptake of neurotransmitters into the nerve terminal terminates synaptic
      transmission at most central synapses and constitutes a key step in the
      modulation of synaptic efficacy. Recently, the cloning of several Na(+)-driven
      neurotransmitter transporters has resulted in the description of a novel family
      of homologous membrane proteins, each with 12 transmembrane segments. These
      transporters constitute major targets of widely used drugs, and modulation of
      transporter gene expression and/or activity may represent an important substrate
      for plasticity in the nervous system.

PMID- 1353463
TI  - Expression of the LH/CG receptor gene in rat ovarian tissue is regulated by an
      extensive alternative splicing of the primary transcript.
AB  - Luteinizing hormone/chorionic gonadotropin (LH/CG) receptor complementary DNA
      (cDNA) isoforms were amplified using pseudopregnant rat ovarian total RNA as a
      template and the primers reaching over the coding regions at both ends in a
      reverse transcriptase-polymerase chain reaction (RT-PCR). Agarose gel
      electrophoresis of the PCR products revealed three bands corresponding to about
      2.1, 2.0 and 1.8 kilobases (kb). Subcloning of pooled PCR products into EcoRI
      site of pUCBM20 resulted in 167 clones, from which five different restriction
      patterns were obtained by digestion with EcoRI and HaeIII. One clone of each was
      further characterized. It could be predicted from the nucleotide sequences that
      the clone rLHR2100 encoded a full-length receptor (a 674 amino acid mature
      protein), the clone rLHR2075 lacked part of exon IX (nucleotides 693-717) and
      encoded a truncated 225 amino acid mature protein, the clone rLHR1950 lacked
      exons III and IV (nucleotides 246-395) and encoded a nearly full-length protein
      (a 624 amino acid mature protein), and the clones rLHR1834 and rLHR1759 lacked
      the same part of exon XI (nucleotides 960-1225), with exon V (nucleotides 396
      470) also absent in the latter, the deletion in exon XI leading both these clones
      to premature termination. The clone rLHR1834 encoded a 316 amino acid mature
      protein and rLHR1759 a 291 amino acid mature protein, respectively. The sequence
      data suggest that all of these isoforms contain the putative signal sequence and
      are derived from a single copy gene via alternative splicing. These results point
      further to the fact that the expression of the 90 kDa LH/CG receptor is regulated
      via an extensive alternative splicing of the receptor gene primary transcript.

PMID- 1353464
TI  - The effects of peptide histidine isoleucine on antral gastrin and somatostatin.
AB  - The present studies were directed to determine whether peptide histidine
      isoleucine (PHI) affects expression of the gastrin and somatostatin genes and
      whether such effects may be functionally linked. In separate experiments, the
      effects of PHI on medium gastrin and somatostatin concentrations, the
      incorporation of 35S-labelled amino acids into newly synthesized gastrin and
      somatostatin, and steady state gastrin and somatostatin mRNA were determined. PHI
      inhibited basal expression of the gastrin gene at all levels examined, while no
      significant effect on basal somatostatin gene expression could be detected. PHI
      also decreased carbachol-stimulated antral gastrin release and simultaneously
      increased somatostatin release. However, in contrast to its structural analogues,
      secretin and gastric inhibitory peptide, the immunoneutralization of endogenous
      somatostatin by the administration of specific antibodies did not affect
      significantly the capacity of PHI to inhibit gastrin release into the culture
      medium stimulated by carbachol. The results of these studies indicate that PHI
      exerts a physiological inhibitory effect on antral gastrin cells and that this
      inhibition may occur at several steps along the biosynthetic pathway. In
      addition, unlike its structural analogues, PHI inhibition of carbachol-stimulated
      gastrin release is not functionally linked to its stimulatory effects on
      somatostatin release.

PMID- 1353465
TI  - Gastroprotective and ulcer-healing activities of a new H2-receptor antagonist:
      ebrotidine.
AB  - Ebrotidine is a novel H2-receptor antagonist that exhibits both gastroprotective
      and ulcer-healing properties. Gastroprotection afforded by ebrotidine against
      ethanol damage was observed only after intragastric, but not parenteral
      administration, and it was accompanied by an increase in the mucosal blood flow.
      Ranitidine given at the same dose (100 mg/kg i.g. or s.c.) did not show any
      protective activity. When administered twice daily at various doses (1-100 mg/kg)
      for 10 days, ebrotidine reduced dose dependently the area of chronic gastric
      ulcers, and it was accompanied by significantly higher contents of epidermal
      growth factor (EGF) in the ulcer bed than in the intact mucosa. Administration of
      ranitidine resulted in a similar rate of ulcer healing and in a similar
      accumulation of EGF in the ulcer area to that observed after ebrotidine, but the
      increments in plasma gastrin levels in rats treated with ranitidine were observed
      at lower doses than in tests with ebrotidine. Concurrent administration of
      indomethacin delayed ulcer healing and reduced the accumulation of EGF in the
      ulcer area, but did not affect the ulcer healing by ebrotidine or ranitidine. We
      conclude that ebrotidine but not ranitidine shows gastroprotective activity, but
      it enhances the healing of chronic ulcerations in a similar manner to ranitidine.

PMID- 1353466
TI  - Effect of aspirin and indomethacin on epidermal growth factor secretion in
      duodenal tissue fragments cultivated in vitro.
AB  - The aim of the present study was to determine the effect of aspirin and
      indomethacin on epidermal growth factor (EGF) secretion in duodenal tissue
      fragments cultivated in vitro. The fragments were obtained from healthy subjects
      by gastroscopy, cultured in McCoy's medium and gassed with 95% O2 and 5% CO2 at
      37 degrees C. After an incubation of 30 min, the culture medium was decanted, and
      the quantity of hormone determined by radioimmunoassay. The mean EGF level
      detected in the medium was 10.94 ng/mg protein tissue. The addition of aspirin
      (final concentration 10(-7) M) to the medium reduced mean EGF levels to 7.5 ng/mg
      (p less than 0.05), whereas aspirin 10(-8) M did not produce such a modification.
      The addition of indomethacin (final concentration 10(-8) M) decreased mean EGF
      levels to 5.37 ng/mg (p less than 0.001). In all experimental conditions, the
      addition of anti-somatostatin (SRIF) antibodies determined a remarkable increase
      in EGF (p less than 0.01). The results of this study show aspirin and
      indomethacin to be direct, not SRIF-mediated inhibitors of EGF release.

PMID- 1353467
TI  - Diversity among mouse motor nerve terminals with respect to release transmitter
      quanta.
AB  - 1. The aim of this work was to reexamine whether a positive correlation exists
      between the frequency (F, sec-1) of miniature endplate potentials (m.e.p.ps) and
      the quantal content (m) of endplate potentials (e.p.ps) or between quantal
      content, frequency and twin-pulse facilitation of transmitter release at a large
      number of neuromuscular junctions in the mouse. 2. The values of F and m were
      both measured intracellularly at endplates of mouse diaphragm in a high Mg2+/low
      Ca2+ bathing solution. 3. Values of both F and m varied from junction to
      junction. Smaller values of F were correlated with smaller values of m, and vice
      versa, resulting in a linear relationships. Histograms of F and m were skewed
      towards smaller values. 4. E.p.ps evoked by twin pulses gave the quantal contents
      of the first (m1) and second (m2) responses. 5. The ratio of m2 to m1 varied from
      junction to junction. A histogram of this ratio was skewed towards smaller
      values. 6. The ratio of m2 to m1 showed larger fluctuations at junctions with
      smaller values of F or m1 but was focused around 1 at junctions with larger
      values of F or m1. 7. The skewed parts of the histograms of F, m and m2/m1
      accounted for the major population of junctions. 8. These results support the
      hypothesis that an intrinsic ability to release transmitter plays a role in
      regulation of the evoked output of transmitter at neuromuscular junctions in the
      mouse. 9. Such an ability is not correlated with the twin-pulse facilitation of
      transmitter release.

PMID- 1353468
TI  - Interaction of tertatolol at the "atypical" or beta 3-adrenoceptor in guinea-pig
      ileum.
AB  - 1. Experiments were performed to investigate the possible interaction between
      tertatolol and the "atypical" beta-adrenoceptor present in guinea-pig ileum. 2.
      In the electrically field stimulated guinea-pig ileum, both isoprenaline and BRL
      37344 produce concentration-dependent inhibition of the "twitch" response. 3.
      Schild regression analysis of the interaction between isoprenaline and tertatolol
      indicated two sites of action and yielded an apparent pA2 value for tertatolol of
      6.8 at the "atypical" beta-adrenoceptor. 4. BRL-37344 selectively activated the
      "atypical" beta-adrenoceptor and tertatolol again yielded an apparent pA2 value
      of 6.7 and 6.8.

PMID- 1353469
TI  - Vasodilatation of canine cerebral arteries by nicorandil, pinacidil and
      lemakalim.
AB  - 1. Nicorandil, pinacidil and lemakalim relaxed precontracted rings of canine
      cerebral artery. 2. The order of potency was lemakalim greater than nicorandil
      approximately equal to pinacidil, but all these agents were less effective than
      nimodipine. 3. The effects of nicorandil were inhibited by methylene blue but not
      by glibenclamide, while the effects of pinacidil and lemakalim were inhibited by
      glibenclamide but not by methylene blue. 4. Thus nicorandil probably causes
      relaxation mostly by effects on guanylate cyclase while lemakalim and pinacidil
      produce the same effect by action at ATP-dependent potassium channels.

PMID- 1353470
TI  - [Restriction polymorphism of mitochondrial DNA among Russian residents of Western
      Siberia].
AB  - Hereditary polymorphism of mitochondrial DNA is described for 5 restriction
      enzymes: BamHI, HindIII, PstI, PvuII and SacI in 60 Russian individuals living in
      Tomsk. 13 morphotypes of mitochondrial DNA were revealed as a whole for the
      enzymes analysed. Comparative analysis of mitochondrial DNA morphs and
      morphotypes with the literature data was conducted.

PMID- 1353471
TI  - [DNA polymorphism in the Russian population. Analysis of dna restriction fragment
      length polymorphism in seven loci of the nuclear genome].
AB  - Using the method for polymerase chain reaction the polymorphism of eight markers
      of the nuclear DNA was studied. In a sample of Russians taken at random (N = 118)
      from predominantly southern and central regions of Russia, allele frequencies
      were determined for restriction sites HindIII at HBG-2 and PAH loci, AvaII at the
      HBB locus, MspI at the ApoB locus, PstI at D7S8, HincII at LDLR, TaqI and BamHI
      at the DSX164. Comparative data for different world regions are presented.

PMID- 1353472
TI  - Structure and lens expression of the gene encoding chicken beta A3/A1-crystallin.
AB  - The beta A1- and beta A3-crystallins are major polypeptides in the lenses of
      vertebrates. We present evidence that a single beta A3/A1 gene encodes these two
      proteins in the chicken. The beta A3/A1 gene has been sequenced and its
      functional promoter identified in transfection experiments. The chicken beta
      A3/A1 gene has the same structure as the human orthologue: six exons with
      standard splice sites and two alternative start codons from which the protein
      products are apparently translated. Northern analysis revealed an abundant 0.9-kb
      transcript in the lenses of 1-2-day-old chickens and no detectable transcripts in
      the rest of the eye, brain, heart, kidney, liver or skeletal muscle. The 5'
      flanking sequence of the chicken beta A3/A1 gene is very similar to that of the
      human and mouse genes, suggesting conservation of important putative regulatory
      sequences in addition to the TATA box. A thymidine-rich element (bp -218 to -163)
      and a potential AP-1-binding site (bp -264 to -258) are present within the
      chicken 5'-flanking region. A DNA fragment from -382 to +22 of the chicken beta
      A3/A1 gene is sufficient to promote expression of the bacterial cat gene in
      transfected chicken primary lens epithelial cells, but not in transfected dermal
      fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353473
TI  - Identification and partial characterization of a somatostatin-14 binding protein
      on rat liver plasma membranes.
AB  - Binding of somatostatin-14 to rat liver plasma membranes was characterized with
      125-labeled[tyr11] somatostatin-14. Binding at 24 degrees C reached a plateau at
      50 min and was reversible by synthetic somatostatin-14. Scatchard analysis
      revealed a single class of binding sites (affinity constant = 2.4 +/- 0.2 nmol/L,
      binding capacity = 148 +/- 0.02 fmol/mg protein). Specificity for somatostatin-14
      was demonstrated by the inhibition of 125I-[tyr11]somatostatin-14 binding by
      biologically active somatostatin analogs but not by a biologically inactive
      somatostatin analog or unrelated peptides. The radioiodinated binding site
      complex could be cross-linked with disuccinimidyl suberate. Analysis by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and gel autoradiography
      revealed a 70,000-Da band. Dithiothreitol, a reducing reagent, did not alter the
      mobility of the band, and the band could be abolished in the presence of 10
      mumol/L synthetic somatostatin-14. Covalently cross-linked, iodinated binding
      protein complexes could be solubilized by the nonreducing detergents Zwittergent
      3-12 and 3-([3-cholamidopropyl] diethylammonio)-1-propanesulfonic acid (CHAPS).
      Solubilized complex bound to wheat-germ agglutinin-agarose columns and was eluted
      by N,N',N"-triacetylchitotriose. Binding to wheat-germ agglutinin agarose columns
      was lost after pretreatment with endo-beta-N-acetylglucosaminidase F. Binding
      studies with liver plasma membranes, 125I-labeled[tyrosine11]somatostatin-14 and
      guanine nucleotides showed inhibition of binding in the presence of guanine
      nucleotides. These results indicate that the purified rat liver plasma membranes
      contain a specific binding protein for somatostatin-14, the binding protein
      appears to be glycosylated and somatostatin-14 binding to rat liver plasma
      membranes may be regulated by G proteins.

PMID- 1353474
TI  - Isolation and high-resolution mapping of new DNA markers from the pericentromeric
      region of chromosome 10.
AB  - The gene responsible for multiple endocrine neoplasia type 2A (MEN 2A) has been
      localized to the pericentromeric region of chromosome 10. Several markers that
      fail to recombine with MEN2A have been identified, including D10Z1, D10S94,
      D10S97, and D10S102. Meiotic mapping in the MEN2A region is limited by the
      paucity of critical crossovers identified and by the dramatically reduced rates
      of recombination in males. Additional approaches to mapping loci in the
      pericentromeric region of chromosome 10 are required. We have undertaken the
      generation of a detailed physical map by radiation hybrid mapping. Here we report
      the development of a radiation hybrid panel and its use in the mapping of new DNA
      markers in pericentromeric chromosome 10. The radiation-reduced hybrids used for
      mapping studies all retain small subchromosomal fragments that include both
      D10S94 and D10Z1. One hybrid was selected as the source of DNA for cloning. One
      hundred five human recombinant clones were isolated from a lambda library made
      with pp11A DNA. We have completed regional mapping of 22 of those clones using
      our radiation hybrid mapping panel. Seven markers have been identified and, when
      taken together with previously meiotically mapped markers, define eight radiation
      hybrid map intervals between D10S34 and RBP3. The identical order is found for a
      number of these using either the radiation hybrid mapping panel or the meiotic
      mapping panel. We believe that this combination cloning and mapping approach will
      facilitate the precise positioning of new markers in pericentromeric chromosome
      10 and will help in refining further the localization of MEN2A.

PMID- 1353475
TI  - A high-resolution meiotic mapping panel for the pericentromeric region of
      chromosome 10.
AB  - Familial multiple endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited
      cancer syndrome characterized by tumors in tissues derived from the neural crest.
      The disease manifests as medullary carcinoma of the thyroid, pheochromocytoma,
      and hyperparathyroidism. The MEN2A locus has been mapped near the centromere of
      chromosome 10 by linkage analysis. Statistical analyses have not resolved the
      location of MEN2A among several close markers. We have used our family material
      to refine the positions of 36 identified and confirmed crossovers among the
      markers most closely linked to MEN2A. This high-resolution meiotic mapping panel
      will help order loci in this pericentromeric region and narrow the region in
      which MEN2A maps.

PMID- 1353476
TI  - A preliminary linkage map of the chicken genome.
AB  - We have used backcross progeny from a cross between two inbred lines of chickens
      to construct a linkage map of the chicken. The map currently consists of 100
      loci, identified using either anonymous cloned fragments of genomic DNA or
      sequences corresponding to cloned genes. Parent birds were derived from two lines
      of White Leghorn chickens, which differ in susceptibility to a number of
      diseases. Restriction fragment length variants were identified by comparison of
      the DNA of these two parent birds using a panel of seven restriction enzyme
      digests and the segregation pattern observed in progeny of these two birds.
      Restriction fragment length variants were detected for approximately 41% of the
      clones tested, whether these were known genes or random genomic fragments. This
      high level of variability was also reflected in the presence of variation within
      the parental lines for some clones. The overall size of the linkage groups and
      the progressively higher incidence of linkage as further clones were added
      suggests that the map covers the majority of the genome, although it is unlikely
      that there are marker loci on all the microchromosomes. The present map will be
      of use in locating genes affecting disease resistance, but also illustrates the
      relative ease with which such maps for the chicken can be constructed.

PMID- 1353477
TI  - Genomic organization of a polymorphic duplicated region centromeric of HLA-B.
AB  - The region between tumor necrosis factor (TNF) and HLA-B in the central major
      histocompatibility complex (MHC) is polymorphic and associated with several
      autoimmune diseases. The polymorphisms are haplospecific or haplotypic and
      retained within the same MHC ancestral haplotype (AH). We have cloned this region
      from four AHs into lambda bacteriophage and found that a highly polymorphic
      region in the TNF-HLA-B interval is duplicated. Clones from this region isolated
      from three MHC AHs show two populations. The regions, designated CL1 and CL2,
      have different sizes of Bam HI fragments carrying the duplicated sequences. These
      fragments correspond to those seen after Bam HI restriction fragment length
      polymorphism (RFLP) analysis of genomic DNA from the same cell lines. Pulsed
      field gel electrophoresis analysis shows that both CL1 and CL2 are in the central
      MHC and are about 16 kilobases apart. DNA cloning and RFLP analysis demonstrate
      that the CL region is highly polymorphic but retained within an MHC AH.
      Polymorphism and duplication are common characteristics of the genes found in the
      MHC and therefore the CL sequences have the potential to be interesting in this
      respect.

PMID- 1353478
TI  - Interaction of H-2Eb with an IAP retrotransposon in the A20/2J B cell lymphoma.
AB  - In the A20/2J BALB/c B cell lymphoma, Southern analysis revealed an insertion of
      approximately 6 kilobases of DNA into the first intron of one Ebd-allele. Two
      observations suggest that the rearrangement did not occur recently in the A20/2J
      subline. Firstly, normal and altered Ebd-alleles are present in equal numbers,
      and secondly, the LB 27.4 and LS 102.9 somatic cell hybrids formed at an earlier
      date both possess the rearrangement. Sequences of two cDNA clones, lambda Eb-7
      and lambda Eb-125, selected from an A20/2J cDNA library prepared from poly [A+]
      RNA indicate that the rearranged Ebd-allele directs the synthesis of atypical Eb
      transcripts. The clones contain Eb sequence linked to a portion of retroviral
      like intracisternal A-particle (IAP) genomic sequence, and they appear to be
      copies of mRNA produced by splicing between a 5' donor site in the retroviral
      transcript and the 3' acceptor site of the Eb gene's first intron. The longer
      lambda Eb-125 insert corresponds to RNA that initiated in the 5'-untranslated
      region of the Eb gene. The 3'-end of the first Eb exon joins to long terminal
      repeat sequence, and retroviral sequence extends up to the splice junction with
      the second Eb exon; 3' of the junction, the lambda Eb-125 sequence corresponds to
      that of a correctly spliced Eb transcript. It seems feasible that the cDNA clones
      represent hybrid RNA synthesized by read-through transcription of the Eb coding
      region and an IAP element inserted into the first intron of the rearranged Ebd
      allele.

PMID- 1353479
TI  - Detection of susceptibility alleles to insulin-dependent diabetes mellitus at the
      DQB1 locus by artificial PCR-RFLP.

PMID- 1353480
TI  - Molecular genotyping of recombinant congenic lines provides evidence for crossing
      over within the B-G region of the major histocompatibility complex of the
      chicken.

PMID- 1353481
TI  - Interaction of capsulate Haemophilus influenzae with human airway mucosa in
      vitro.
AB  - Two pairs of isogenic capsulate and noncapsulate and one pair of capsulate
      fimbriate and nonfimbriate strains of Haemophilus influenzae type b were studied
      in an organ culture of human respiratory mucosa. Over 24 h, the numbers of
      recovered bacteria increased from the original inoculum size of 10(5) to 10(8)
      CFU/ml. Transmission electron microscopy and scanning electron microscopy showed
      that noncapsulate organisms caused significant epithelial damage, whereas
      capsulate strains did not. Association of noncapsulate bacteria with damaged
      epithelial cells was observed by 14 h of incubation. In contrast, capsulate
      organisms were associated with a dense, thick, gel-like matrix which was observed
      above the epithelial surface. These capsulate organisms were not seen to
      associate with the epithelial surface (by transmission electron microscopy),
      though they were occasionally seen adhering to cells by scanning electron
      microscopy. Fimbriate capsulate H. influenzae showed increased adherence to
      buccal cells compared with nonfimbriate capsulate organisms. There was also
      association of fimbriate capsulate bacteria with damaged organ culture epithelium
      in one of four experiments. It is concluded that both capsule and fimbriae affect
      the interaction of H. influenzae with human airway mucosa in vitro by influencing
      adherence to and damage of the epithelium.

PMID- 1353482
TI  - Role of carbohydrate recognition domains of pertussis toxin in adherence of
      Bordetella pertussis to human macrophages.
AB  - Pertussis toxin (PT) and filamentous hemagglutinin can each mediate the
      association of Bordetella pertussis with human macrophages. Adherence via
      filamentous hemagglutinin leads to integrin-mediated entry and survival of the
      bacteria within the human cell. We determined the contribution of PT to bacterial
      adherence to human macrophages. Plating macrophages on wells coated with
      recombinant PT subunit 2 (S2) or S3 decreased PT-dependent bacterial binding by
      greater than 60%; S1, S4, and S5 were ineffective. S3-dependent adherence was
      reduced 63% +/- 8% by sialic acid, while S2-dependent adherence was reduced 53%
      +/- 11% by galactose. Loss of the carbohydrate recognition properties of S2 by
      deletion of residues 40 to 54 or site-specific mutations at Asn-93, His-47, or
      Arg-50 eliminated the ability of the subunit protein to competitively inhibit
      bacterial binding. Peptides corresponding to residues 28 to 45 of S2 and S3
      competitively inhibited adherence. Treatment of macrophages with antibodies to
      Le(a) or Le(x) but not CD14, CD15, CD18, or HLA interfered with PT-mediated
      binding. Exposure of the macrophages to the B oligomer, S2, or S3 increased
      binding to the CD11b/CD18 integrin. These results indicate that the carbohydrate
      recognition domains of both S2 and S3 participate in adherence of B. pertussis to
      human macrophages. The PT receptor(s), as yet unidentified, appears to carry the
      Le(a) or Le(x) determinants and is functionally capable of modulating integrin
      mediated binding to the macrophage.

PMID- 1353484
TI  - Identification of type 4 pili in Kingella denitrificans.
AB  - Kingella denitrificans is an occasionally pathogenic member of the family
      Neisseriaceae and is a member of the normal respiratory flora. Electron
      microscopy, colony morphology types, DNA transformation patterns, and immunoblots
      suggest that K. denitrificans and K. kingae have type 4 pili. This was confirmed
      by N-terminal amino acid sequencing for K. denitrificans.

PMID- 1353483
TI  - Roles of the pap- and prs-encoded adhesins in Escherichia coli adherence to human
      uroepithelial cells.
AB  - In this study, we reexamined the structural prerequisites for the attachment of P
      fimbriated Escherichia coli to human urinary tract epithelial cells. The
      epithelial cells were obtained from A1P1 nonsecretor individuals, who express the
      globoseries of glycolipids without the ABH blood group determinants, and from
      A1P1 secretor individuals, who in addition express globo-A, a receptor for the
      prsJ96 adhesin. The wild-type E. coli strains J96, AD110, and IA2 and the
      recombinant clones HB101 papJ96, HB101 prsJ96, HB101 papIA2, and HB101 papAD110
      were tested for binding. They expressed P fimbriae, as defined by P blood group
      dependent agglutination of human erythrocytes of the globoseries, but differed in
      reactivity with galactose alpha 1-4galactose beta (Gal alpha 1-4Gal beta)-latex
      beads, isolated glycolipids of the globoseries, sheep erythrocytes, and
      uroepithelial cells. Three different patterns of binding were represented among
      the recombinant clones. HB101 papIA2 and HB101 papAD110 agglutinated sheep
      erythrocytes and Gal alpha 1-4Gal beta-latex beads and attached to both secretor
      and nonsecretor epithelial cells. HB101 prsJ96 agglutinated sheep erythrocytes,
      reacted poorly with Gal alpha 1-4Gal beta-latex beads, and attached to A1
      secretor but not to A1 nonsecretor epithelial cells. HB101 papJ96 agglutinated
      Gal alpha 1-4Gal beta-latex beads but not sheep erythrocytes and attached poorly
      to human uroepithelial cells. The receptors relevant for adhesion were analyzed
      by inhibition with glycolipids in suspension. The sheep erythrocyte agglutination
      and attachment to secretor and nonsecretor epithelial cells of HB101 papIA2 and
      HB101 papAD110 were inhibited by globotetraosylceramide, while the Forssman
      glycolipid had no effect. The sheep erythrocyte reactivity and attachment to
      secretor epithelial cells of HB101 prsJ96 were inhibited by the Forssman
      glycolipid. These results permitted three conclusions. First, the expression of
      functionally active Gal alpha 1-4Gal beta-specific adhesins, as in HB101 papJ96,
      was not sufficient to make E. coli competent to attach to human uroepithelial
      cells. Attachment required P fimbriae of the papIA2 or papAD110 type. Second, the
      sheep erythrocyte reactivity of P-fimbriated strains could not be attributed
      solely to recognition of the Forssman glycolipid and may not be used to define
      the prsJ96-encoded phenotype. Third, the P-fimbrial adhesins which mediate
      secretor state-independent attachment to human uroepithelial cells recognized
      receptor epitopes provided by globotetraosylceramide.

PMID- 1353485
TI  - Expression of c-sis and c-fos genes in human meningiomas and neurinomas.
AB  - The HindIII c-sis RFLP was analyzed in constitutional and tumor DNAs of 19
      meningioma patients. Loss of a c-sis allele (allele I in all cases) was observed
      in 6 out of 10 tumors from heterozygous patients. No alteration in the structure
      or dosage of the c-sis gene was detected in any tumor sample. Northern analysis
      of c-sis evidenced sis transcripts in 7 out of 8 meningiomas which were amenable
      to analysis. All tumors expressing c-sis also expressed c-fos, suggesting that
      the autocrine loop elicited by sis activation may have c-fos as its nuclear
      target. Co-expression of c-sis and c-fos was also observed in 5 neuromas out of 7
      analyzed. Very high levels of fos-mRNA were observed in 2 neuromas, but were not
      found to be caused by apparent alteration or amplification of the c-fos gene.

PMID- 1353486
TI  - Epinephrine increases facility of outflow and cyclic AMP content in the human eye
      in vitro.
AB  - The physiologic mechanism that underlies the epinephrine-induced increase in
      facility of outflow (C) in glaucomatous human eyes and normal primate eyes is not
      completely understood. In this study, a recently developed in vitro human eye
      perfusion model was used to simultaneously monitor facility and cyclic adenosine
      monophosphate (AMP) changes in response to epinephrine (EPI). In this system, EPI
      (2.5 x 10(-5) mol/l) resulted in a maximal 44% increase in C, with an ED50
      occurring at approximately 8 x 10(-6) mol/l. The C-increasing effect of 10(-5)
      mol/l EPI was unaffected by 10(-6) mol/l phentolamine. However, it was completely
      blocked in the presence of 10(-6) mol/l timolol or 2 x 10(-7) mol/l ICI118,551,
      suggesting the involvement of beta-2 adrenergic receptors. In biochemical
      studies, 10(-5) mol/l EPI induced a 12- to 14-fold increase in cyclic AMP in the
      perfusate of treated eyes. This increase was blocked by ICI118,551. In isolated
      intact human trabecular tissue, a 10 min incubation with 10(-5) EPI stimulated
      cyclic AMP by a factor of 2.7 over control levels. After 90 min, cyclic AMP
      levels were increased 4.2 fold over control levels. Collectively, these results
      show that the intraocular pressure lowering effect of EPI in the human eye is
      mediated, at least in part, by an increase in facility of outflow. Furthermore,
      the facility increase appears to be mediated by beta-2 adrenergic receptors and
      is correlated in time with increased cyclic AMP production.

PMID- 1353487
TI  - Association between IgE response against Bet v I, the major allergen of birch
      pollen, and HLA-DRB alleles.
AB  - The association of the human IgE response against Bet v I, the major allergen of
      birch pollen, and the HLA-DR and DQ phenotype was studied. Birch pollen allergic
      patients showed a typical case history, positive skin-prick test, and positive
      RAST with birch pollen extracts. They were divided into two groups. Group I (n =
      37) consisted of individuals generating IgE antibodies that selectively reacted
      with Bet v I. Their serum IgE did not react with minor allergens from birch
      pollen as tested by immunoblot analysis, nor did they show a response against
      allergens from a panel of grass and other tree pollen or perennial allergens from
      animals and fungi as determined by skin-prick test. Patients belonging to group
      II (n = 34) possessed IgE reacting with Bet v I plus one or more additional
      allergens. The control group consisted of 637 healthy blood donors. Comparison of
      the frequencies of RFLP-defined HLA-DR and DQ alleles in patients and the control
      group revealed that the distribution of DRB3 alleles in group I patients differed
      significantly from that in the control group: A higher frequency of the DRw52a/c
      alleles in comparison to the control group (pcorr less than 0.02) was observed.
      In addition, alleles defined by nucleotide sequences coding for the amino acid
      sequence tyrosine-phenylalanine-histidine at positions 30-32 of the beta chain of
      DR molecules were found with a higher frequency in patient group I (pcorr less
      than 0.02), too. These alleles comprise DRw52a/c and some DRB1 alleles.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1353488
TI  - Molecular characterization of a recombinant HLA-DR1/DR2 haplotype.
AB  - Serologic analysis of two families identified an HLA-DR haplotype in which DR1
      and DR2 cosegregated. DNA-RFLP analysis of these families with an HLA-DRB probe
      revealed a pattern of hybridization suggestive of a recombination between DR1 and
      DR15. Following amplification, cloning, and nucleotide sequencing of HLA-DRB-gene
      second-exon DNA sequences, three DRB amplification products associated with the
      novel haplotype were identified: these corresponded to DRB1*0101, DR2 pseudogene,
      and DRB5*0101. Clones representing the DRB1*1501 and DR1 pseudogenes were not
      identified: oligonucleotide typing with DRB1*1501-specific probes confirmed the
      absence of this gene within the DR1/DR2 haplotype. We postulate that the DR1/DR2
      haplotype represents a recombinant between those of DR1-Dw1 and DR15-Dw2, and
      that the crossing-over may have been between the DRB1*0101 gene and the DR2
      pseudogene. This is further supported by DNA-RFLP analysis with HLA-DQB and DQA
      CDNA probes, which revealed conserved linkage genes between the DQB1*0501,
      DQA1*0101, and DRB1*0101 genes.

PMID- 1353489
TI  - Therapy of small breast cancer: a prospective study on 1036 patients with special
      emphasis on prognostic factors.
AB  - In 1983, The German Breast Cancer Study Group, sponsored by the Federal Ministry
      of Research and Technology, started a prospective multicenter trial on the
      treatment of early breast cancer pT1 pN0 M0. Treatment consisted of initial
      tumorectomy with microscopically free margins and lower axillary dissection.
      After conformation of a pT1 pN0-stage, additional treatment was either mastectomy
      or adjuvant radiotherapy (50 Gy in 25 fractions to the entire breast plus 12 Gy
      electron boost). In medially located tumors, the parasternal and supraclavicular
      area was also irradiated with 50 Gy. A randomization between both treatment
      modalities was initially planned but was not feasible and abandoned. Nearly all
      patients were treated according to their own choice. From November 1983 through
      December 1989, 1119 patients were recruited. Eighty-three were excluded from the
      protocol. Out of the remaining 1036 patients, 733 (71%) underwent breast
      preservation and 303 (29%) mastectomy. A detailed pathohistological examination
      of all tumorectomy specimens was performed in a pathologic reference center.
      Oncogen overexpression was evaluated by immunohistological detection of the
      transmembrane protein p-185 (corresponding to c-erb-B2) in 425 cases. After a
      median follow-up of 48 months, the frequency of local recurrences (4.7%),
      regional recurrences (1%), and distant metastases (5.4%) was the same in the
      breast preservation group and the mastectomy group. The 3-year disease-free
      survival was 90% after breast preservation and 88% after mastectomy (p = 0.21).
      In the breast preserving group, 24 patients with microscopically involved margins
      had a poorer disease-free survival than the study group (75% vs 90% after 3
      years). The width of the margins had no impact on prognosis. Other prognostic
      factors in an univariate and multivariate analysis were tumor size and tumor
      grade. Age, menopausal status, hormone receptor status, histological tumor type,
      and treatment (mastectomy vs breast preservation) were not significant. P-185
      expression was dependent on tumor grade and was the strongest prognostic factor
      in an univariate and multivariate analysis (p less than 0.001). The results
      emphasize the central role of tumor grade for prognosis and suggest the
      independent prognostic significance of the c-erb-B2 oncogen (corresponding to p
      185) in pN0-patients.

PMID- 1353490
TI  - Reports from Symposia on Circulatory Shock and Cardiopulmonary Resuscitation.

PMID- 1353491
TI  - Current issues on asthma drugs: impact on clinical trial methodology.

PMID- 1353493
TI  - Injection site reactions.

PMID- 1353492
TI  - Should chronic treatment-refractory akathisia be an indication for the use of
      clozapine in schizophrenic patients?
AB  - BACKGROUND: Clozapine, an atypical neuroleptic, is an effective medication in a
      subgroup of schizophrenic patients who have either failed to respond to the
      typical neuroleptics or experienced intolerable side effects such as neuroleptic
      malignant syndrome and disabling tardive dyskinesia. Its efficacy for persistent
      and disabling akathisia is less clear. Akathisia, especially the chronic and
      disabling form, can be a treatment dilemma for the clinician and the patient.
      METHOD: We describe three representative case illustrations of schizophrenic
      patients who had severe, persistent treatment-resistant akathisia. Two of them
      had refractory psychoses and the third had multiple disabling side effects during
      treatment with typical neuroleptics. Two had tardive dyskinesia. These patients
      were treated with clozapine while other neuroleptics were discontinued. RESULTS:
      During a 2-year follow-up, these patients made impressive social and vocational
      strides coinciding with a fairly rapid remission of akathisia (under 3 months)
      and a lesser though notable improvement in the psychoses. Tardive dyskinesia also
      remitted, though over a period of 6 to 12 months. CONCLUSION: Our experience
      leads us to suggest a trial of clozapine in a subgroup of schizophrenic patients,
      who in addition to refractory psychoses have persistent disabling akathisia.
      However, given the risk of agranulocytosis with clozapine, we suggest that the
      usual treatment strategies for akathisia be tried before clozapine is initiated
      in the approved manner. Future controlled trials of clozapine that specifically
      investigate persistent akathisia may answer this question more conclusively.

PMID- 1353494
TI  - Glutamate transport into synaptic vesicles. Roles of membrane potential, pH
      gradient, and intravesicular pH.
AB  - Glutamate, the major excitatory neurotransmitter in the mammalian central nervous
      system, is transported into bovine synaptic vesicles in a manner that is ATP
      dependent and requires a vesicular electrochemical proton gradient. We studied
      the electrical and chemical elements of this driving force and evaluated the
      effects of chloride on transport. Increasing concentrations of Cl- were found to
      increase the steady-state ATP-dependent vesicular pH gradient (delta pH) and were
      found to concomitantly decrease the vesicular membrane potential (delta psi). Low
      millimolar chloride concentrations, which cause 3-6-fold stimulation of vesicular
      glutamate uptake, caused small but measurable increases in delta pH and decreases
      in delta psi, when compared to control vesicles in the absence of chloride.
      Nigericin in potassium buffers was used to alter the relative proportions of
      delta pH and delta psi. Compared to controls, at all chloride concentrations
      tested, nigericin virtually abolished delta pH and increased the vesicle interior
      positive delta psi. Concomitantly, nigericin increased ATP-dependent glutamate
      uptake in 0-1 mM chloride but decreased glutamate uptake in 4 mM (45%), 20 mM
      (80%), and 140 mM (75%) Cl- (where delta pH in the absence of nigericin was
      large). These findings suggest that either delta psi, delta pH, or a combination
      can drive glutamate uptake, but to different degrees. In the presence of 4 mM Cl
      , where uptake is optimal, both delta psi and delta pH contribute to the driving
      force for uptake. When the extravesicular pH was increased from 7.4 to 8.0, more
      Cl- was required to stimulate vesicular glutamate uptake. In the absence of Cl-,
      as extravesicular pH was lowered to 6.8, uptake was over 3-fold greater than it
      was at pH 7.4. As extravesicular pH was reduced from 8.0 toward 6.8, less Cl- was
      required for maximal stimulation. Decreasing the extravesicular pH from 8.0 to
      6.8 in the absence of Cl- significantly increased glutamate uptake activity, even
      though proton-pumping ATPase activity actually decreased about 45% under
      identical conditions. In the absence of chloride, nigericin increased glutamate
      uptake at all the pH values tested except pH 8.0. Glutamate uptake at pH 6.8 in
      the presence of nigericin was over 6-fold greater than uptake at pH 7.4 in the
      absence of nigericin. We conclude from these experiments that optimal ATP
      dependent glutamate uptake requires a large delta psi and a small delta
      pH.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1353496
TI  - Assembly of plant ferredoxin-NADP+ oxidoreductase in Escherichia coli requires
      GroE molecular chaperones.
AB  - We have recently reported the expression in Escherichia coli of an enzymatically
      competent ferredoxin-NADP+ oxidoreductase from cloned pea genes encoding either
      the mature enzyme or its precursor protein (Ceccarelli, E. A., Viale, A. M.,
      Krapp, A. R., and Carrillo, N. (1991) J. Biol. Chem. 266, 14283-14287).
      Processing to the mature form by bacterial protease(s) and FAD assembly occurred
      in the bacterial cytosol. Expression of ferredoxin-NADP+ reductase in chaperonin
      deficient (groE-) mutants of E. coli resulted in partial reductase assembly at
      permissive growth temperatures (i.e. 30 degrees C), and in total breakdown of
      holoenzyme assembly, and accumulation as aggregated inclusion bodies at non
      permissive temperatures (i.e. 42 degrees C). Coexpression in these mutants of a
      cloned groESL operon from the phototrophic bacterium Chromatium vinosum resulted
      in partial or total recoveries of ferredoxin-NADP+ reductase assembly. The
      overall results indicate that bacterial chaperonins are required for the
      productive folding/assembly of eucaryotic ferredoxin-NADP+ reductase expressed in
      E. coli.

PMID- 1353495
TI  - Inhibition by glucagon of the cGMP-inhibited low-Km cAMP phosphodiesterase in
      heart is mediated by a pertussis toxin-sensitive G-protein.
AB  - We have recently reported that glucagon activated the L-type Ca2+ channel current
      in frog ventricular myocytes and showed that this was linked to the inhibition of
      a membrane-bound low-Km cAMP phosphodiesterase (PDE) (Mery, P. F., Brechler, V.,
      Pavoine, C., Pecker, F., and Fischmeister, R. (1990) Nature 345, 158-161). We
      show here that the inhibition of membrane-bound PDE activity by glucagon depends
      on guanine nucleotides, a reproducible inhibition of 40% being obtained with 0.1
      microM glucagon in the presence of 10 microM GTP, with GTP greater than GTP gamma
      S, while GDP and ATP gamma S were without effect. Glucagon had no effect on the
      cytosolic low-Km cAMP PDE, assayed with or without 10 microM GTP. Glucagon
      inhibition of membrane-bound PDE activity was not affected by pretreatment of the
      ventricle particulate fraction with cholera toxin. However, it was abolished
      after pertussis toxin pretreatment. Mastoparan, a wasp venom peptide known to
      activate G(i)/G(o) proteins directly, mimicked the effect of glucagon. PDE
      inhibition by glucagon was additive with the inhibition induced by Ro 20-1724,
      but was prevented by milrinone. This was correlated with an increase by glucagon
      of cAMP levels in frog ventricular cells which was not additive with the increase
      in cAMP due to milrinone. We conclude that glucagon specifically inhibits the
      cGMP-inhibited, milrinone-sensitive PDE (CGI-PDE). Insensitivity of
      adenylylcyclase to glucagon and inhibition by the peptide of a low-Km cAMP PDE
      were not restricted to frog heart, but also occurred in mouse and guinea pig
      heart. These results confirm that two mechanisms mediate the action of glucagon
      in heart: one is the activation of adenylylcyclase through Gs, and the other
      relies on the inhibition of the membrane-bound low-Km CGI-PDE, via a pertussis
      toxin-sensitive G-protein.

PMID- 1353497
TI  - Purification of a pituitary receptor for somatostatin. The utility of
      biotinylated somatostatin analogs.
AB  - A somatostatin (SRIF) receptor and its associated Gi regulatory proteins was
      purified from GH4C1 rat pituitary cells by: 1) saturation of the membrane-bound
      receptor with biotinyl-NH-[Leu8,D-Trp22,Tyr25] SRIF28 (bio-S28); 2)
      solubilization of receptor-ligand (R.L) complex with deoxycholate
      lysophosphatidylcholine (D.L); 3) adsorption of solubilized receptor-ligand
      complex to immobilized streptavidin; and 4) elution of receptor and G-protein by
      GTP. The receptor, a glycoprotein with an average M(r) of 85,000, was then
      purified to substantial homogeneity on immobilized wheat germ agglutinin. The 85
      kDa glycoprotein was identified as a SRIF receptor by several criteria. (a) It
      had the same size as the chemically cross-linked R.[125I]L complex. (b) Yield of
      the purified protein increased and plateaued in the same range of bio-S28
      concentrations where specific high affinity binding reached saturation. (c) It
      was copurified with appropriate G-protein subunits. The 85-kDa receptor and two
      other proteins with M(r) values of 35,000 and 40,000, the sizes of G beta and G
      alpha, did not appear in eluates from control streptavidin columns done with SRIF
      receptors loaded with nonbiotinylated S14. The 40-kDa protein was identified as a
      Gi alpha by ADP-ribosylation from [32P]NAD catalyzed by pertussis toxin. (d) Both
      the chemically cross-linked R.[125I]L complex and SRIF receptor purified from
      [35S]methionine-labeled GH4C1 cells were reduced in size to about 38 kDa by
      endoglycosidase F. (e) Amino acid sequence from the purified receptor was nearly
      identical with that of a recently cloned SRIF receptor subtype.

PMID- 1353498
TI  - Solubilization and partial purification of somatostatin-28 preferring receptors
      from hamster pancreatic beta cells.
AB  - Somatostatin-28 (SRIF-28) preferring receptors were solubilized from hamster beta
      cell insulinoma using the zwitterionic detergent 3-[(3-cholamidopropyl)
      dimethylammonio]-1-propanesulfonate. The binding of the iodinated [Leu8-D-TRP22
      Tyr25]SRIF-28 analog (referred to as 125I[LWY] SRIF-28) to the solubilized
      fraction was time-dependent, saturable, and reversible. Scatchard analysis of
      equilibrium binding data indicated that the solubilized extract contained two
      classes of SRIF-28-binding sites: a high affinity site (Kd = 0.3 nM and Bmax = 1
      pmol/mg protein) and a low affinity site (Kd = 13 nM and Bmax = 4.7 pmol/mg
      protein). The binding of 125I[LWY]SRIF-28 to solubilized SRIF-28 receptors was
      sensitive to the GTP analog guanosine-5'-O-thiotriphosphate, suggesting that
      receptors are functionally linked to a G-protein. By anion-exchange
      chromatography of the solubilized extract followed by chromatography on wheat
      germ agglutinin, a 46-fold purification of SRIF-28 receptors was obtained. At
      this stage of purification, only high affinity sites were found (Kd = 1 nM) and
      the GTP effect was not maintained. A specific protein of 37 kDa was identified by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis after photoaffinity
      labeling. We suggest that this protein is the putative SRIF-28 receptor or a
      subunit thereof.

PMID- 1353499
TI  - Transient aggregation of nascent thyroglobulin in the endoplasmic reticulum:
      relationship to the molecular chaperone, BiP.
AB  - Because of its unusual length, nascent thyroglobulin (Tg) requires a long time
      after translocation into the endoplasmic reticulum (ER) to assume its mature
      tertiary structure. Thus, Tg is an ideal molecule for the study of protein
      folding and export from the ER, and is an excellent potential substrate for
      molecular chaperones. During the first 15 min after biosynthesis, Tg is found in
      transient aggregates with and without interchain disulfide bonds, which precede
      the formation of free monomers (and ultimately dimers) within the ER. By
      immunoprecipitation, newly synthesized Tg was associated with the binding protein
      (BiP); association was maximal at the earliest chase times. Much of the Tg
      released from BiP by the addition of Mg-ATP was found in aggregates containing
      interchain disulfide bonds; other BiP-associated Tg represented non-covalent
      aggregates and unfolded free monomers. Importantly, the immediate precursor to Tg
      dimer was a compact monomer which did not associate with BiP. The average
      stoichiometry of BiP/Tg interaction involved nearly 10 BiP molecules per Tg
      molecule. Cycloheximide was used to reduced the ER concentration of Tg relative
      to chaperones, with subsequent removal of the drug in order to rapidly restore Tg
      synthesis. After this treatment, nascent Tg aggregates were no longer detectable.
      The data suggest a model of folding of exportable proteins in which nascent
      polypeptides immediately upon translocation into the ER interact with BiP. Early
      interaction with BiP may help in presenting nascent polypeptides to other helper
      molecules that catalyze folding, thereby preventing aggregation or driving
      aggregate dissolution in the ER.

PMID- 1353500
TI  - Bethanechol inhibition of chicken intestinal brush border Na/H exchange: role of
      protein kinase C and other calcium-dependent processes.
AB  - Bethanechol, a muscarinic agonist, inhibits the initial rate of amiloride
      sensitive Na uptake by intact mucosa of avian small intestine as well as by
      isolated chicken villus enterocytes, an effect that is maximal at 90 seconds and
      reverses by 6 minutes. Bethanechol similarly decreases intracellular pH in
      isolated cells suspended in bicarbonate-free buffer in a time course similar to
      inhibition of enterocyte Na uptake, suggesting inhibition of Na/H exchange. In
      brush border membrane vesicles rapidly prepared from cells stimulated with
      bethanechol, proton-dependent 22Na uptake is transiently inhibited in a time
      course similar to inhibition of cell Na uptake. Bethanechol also stimulates
      transient translocation of protein kinase C from the cytosol to the particulate
      fraction, a portion of this activity translocating to the brush border membrane.
      To determine the calcium dependence of bethanechol's action, enterocytes were
      loaded with varying concentrations of the calcium buffering agent quin-2.
      Inhibition of cell Na uptake by the calcium ionophore ionomycin could be
      completely reversed by quin-2 buffering in a concentration-dependent manner. In
      contrast, quin-2 buffering had little or no effect on the inhibition of Na uptake
      caused by the protein kinase C activators phorbol esters and
      oleoylacetylglycerol. Bethanechol's inhibitory effects were partially, but not
      completely reversed by quin-2 buffering. These data suggest that the effects of
      bethanechol on chicken villus enterocyte brush border Na/H exchange are mediated
      by calcium-dependent process(es) as well as by protein kinase C.

PMID- 1353502
TI  - 15th International Symposium on Column Liquid Chromatography. Part II. Basel,
      June 3-7, 1991.

PMID- 1353501
TI  - Metabolic effects of beta 2-agonists.
AB  - Catecholamines produce a number of biochemical changes most of which result from
      stimulation of beta 2-receptors. Interest in these metabolic effects has
      increased recently as a consequence of the concern over the relatively high
      mortality from acute asthma attacks. In this review the data on the impact of
      beta 2-agonists on glucose production, insulin release and lipolysis are
      presented. Thereafter the subject of hypokalaemia, the mechanism for its
      production by beta 2-agonists and its relevance to cardiac arrhythmias are
      considered in detail. Finally the fall in plasma magnesium and the possible role
      of beta 2-agonists in the production of lactic acidosis are discussed.

PMID- 1353503
TI  - Biochemical separation technology. Papers presented at the honorary symposium on
      the occasion of the 70th birthday of Jerker O. Porath. Uppsala, June 16-19, 1991.

PMID- 1353504
TI  - The effect of changing somatostatin tone on the pituitary growth hormone and
      thyroid-stimulating hormone responses to their respective releasing factor
      stimuli.
AB  - Somatostatin (SS) inhibits GH and TSH secretion, but its role in modulating their
      pulsatility is unclear. We studied GH and TSH responses to GH-releasing hormone
      (GHRH) and TRH stimulation upon a variable background infusion of saline, SS-(1
      14) at 20 and 100 micrograms/m2.h, and oral pyridostigmine (30 and 60 mg) in six
      adult males. Basal GH levels were unaffected by SS-(1-14). Deconvolution analysis
      of serum GH values demonstrated that the pituitary responded to two GHRH stimuli
      90 min apart without attenuation of the second response. The higher dose of SS-(1
      14) significantly blunted the first GH response; second GH responses were further
      attenuated by both SS-(1-14) doses. Maximum GH release and "switch-off" rates for
      both stimuli were reduced without changes in the 50% secretion time.
      Pyridostigmine enhanced the first GH response to GHRH with an increase in the GH
      release rate; second GH responses were not augmented. GH secretion was prolonged
      by pyridostigmine, although the 50% secretion time remained unchanged. Peak
      stimulated serum TSH was attenuated by both SS-(1-14) doses, but pyridostigmine
      had no effect. All other TSH parameters examined were unaffected. We conclude
      that the GH response to GHRH is dependent on SS tone, but that the thyrotroph is
      not tonically inhibited by SS. SS attenuates the rate of GH release without
      changing the duration of secretion and appears important in terminating GH
      secretion.

PMID- 1353505
TI  - Somatostatin receptors on thyrotropin-secreting pituitary adenomas: comparison
      with the inhibitory effects of octreotide upon in vivo and in vitro hormonal
      secretions.
AB  - The in vivo and in vitro inhibitory effects of a somatostatin (SRIH) analog,
      octreotide, upon TSH, alpha-subunit, GH, and PRL have been studied, as well as
      SRIH receptors and their coupling to adenylate cyclase, in nine TSH-secreting
      pituitary adenomas. From in vivo and cell culture studies, the TSH- and alpha
      subunit-secreting adenomas appeared heterogeneous, with four out of the nine
      tumors cosecreting GH and/or PRL. A single sc injection of octreotide (100
      micrograms) lowered plasma concentration of TSH by 40 +/- 5% (mean +/- SE of 5),
      of alpha-subunit by 27 +/- 9% (n = 5), of GH by 60 +/- 5% (n = 4), and of PRL by
      27 +/- 9% (n = 4). In cells cultures, octreotide (10(-8) mol/L) inhibited equally
      TSH, alpha-subunit, and GH release. 125I-Tyr0-DTrp8-SRIH binding sites were
      measurable in the nine TSH-secreting adenomas either on membrane preparations (n
      = 6; Bmax: 152 +/- 73 fmol/mg protein) or on frozen sections by radioautography
      (n = 3). Their density was variable among TSH adenomas and was lower than that
      measured in GH-secreting adenomas but higher than in nonfunctioning tumors. Two
      out of three TSH-secreting adenoma displayed an heterogeneous distribution of
      125I-Tyr0-DTrp8-SRIH binding sites. 125I-Tyr0-DTrp8-SRIH specific binding was
      inhibited by guanosine triphosphate (GTP: 10(-4) mol/L). SRIH inhibited adenylate
      cyclase in 5/5 TSH-secreting adenomas and a good correlation (r = 0.92, P less
      than 0.02) was found between 125I-Tyr0-DTrp8-SRIH binding capacity (Bmax) and
      maximal adenylate cyclase inhibition by SRIH. These results demonstrate in vivo
      and in vitro inhibition of TSH, alpha-subunit, PRL, and GH secretion by
      octreotide in TSH-secreting pituitary adenomas. Functional SRIH receptors are
      present on these tumors and the effect of SRIH on hormonal secretion could be
      mediated, at least in part, by inhibition of adenylate cyclase. These findings
      support the medical treatment of this rare type of tumors by SRIH analogs.

PMID- 1353506
TI  - The influence of different beta-blocking drugs on the peripheral circulation in
      Raynaud's phenomenon and in hypertension.
AB  - In a double-blind, randomized, placebo-controlled study, the authors investigated
      the effects of different beta-adrenoceptor blocking drugs on the peripheral
      circulation. A single intravenous injection of the nonselective beta-blocker
      propranolol (0.20 mg/kg), the beta 1-selective adrenoceptor blocker metoprolol
      (0.25 mg/kg), and the nonselective beta-blocker with partial agonistic activity
      (PAA) pindolol (0.04 mg/kg) and of placebo (saline) was given to eight patients
      with a primary Raynaud's phenomenon and to nine untreated patients with primary
      hypertension. The authors measured finger skin temperature (FST), and laser
      Doppler estimated finger skin blood flux (LDF) before, during, and after a
      standardized finger cooling test, performed 25 minutes after the administration
      of the drugs. In both patients groups propranolol, metoprolol, and pindolol had
      no significant effect on FST and LDF in the first 25 minutes after administration
      both in comparison to baseline value and to placebo. Also, no significant
      differences were found in the recoveries of FST and LDF after cold challenge
      between all drugs and placebo in both groups. The authors conclude that no
      adverse effect of any type of beta-adrenoceptor blocker in comparison to placebo
      could be detected after a single administration on both the baseline finger skin
      perfusion and the recovery after cold-induced vasoconstriction. In addition, the
      authors could not demonstrate a favorable effect of beta 1-selectivity or PAA in
      comparison to a nonselective beta-adrenoceptor blocker without PAA, in any group.

PMID- 1353507
TI  - Comparative effects of a new cardioselective beta-blocker nebivolol and
      nifedipine sustained-release on 24-hour ambulatory blood pressure and plasma
      lipoproteins.
AB  - This double-blind, parallel-group study compared the effects of nebivolol, a
      novel cardioselective beta-blocker, with those of nifedipine sustained-release on
      24-hour ambulatory blood pressure and plasma lipoprotein levels. After a washout
      period of 8 weeks, 51 patients with mild to moderate essential hypertension were
      randomized to double-blind treatment with either nebivolol 5 mg once a day (n =
      26) or nifedipine sustained-release 20 mg bid (n = 25) over a period of 12 weeks.
      Both treatments produced similar and significant (P = .0001) reduction in office
      blood pressure as well as in 24-hour, work, awake, and sleep ambulatory blood
      pressure. The clinical response (diastolic blood pressure less than 90 mmHg or
      decreased by greater than or equal to 10 mmHg) rate was 69% for nebivolol and 59%
      for nifedipine, respectively. Moreover, the nebivolol and nifedipine treatment
      induced decreases in mean 24-hour ambulatory blood pressure were similar to the
      decreases in clinic blood pressure. Furthermore, the percentages of "blood
      pressure loads" (awake greater than 140/90 mmHg and asleep greater than 120/80
      mmHg) were lowered significantly (P = .0001), from 60% to 29% with nebivolol and
      from 60% to 39% with nifedipine. Mean ambulatory heart rate was reduced (P =
      .0001) from 79 +/- 7 to 68 +/- 7 beats/minute during nebivolol therapy and from
      80 +/- 9 to 79 +/- 7 (not significant) with nifedipine. Total plasma cholesterol
      and low-density lipoprotein levels decreased significantly (P less than .05) by 5
      and 8%, respectively, after nebivolol treatment, and each decreased by 3% after
      nifedipine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353508
TI  - Conventional screening for enteropathogenic Escherichia coli in the UK. Is it
      appropriate or necessary?
AB  - Enteropathogenic Escherichia coli (EPEC) is a well-recognized cause of infantile
      diarrhoea in the developing countries. In the developed countries, however, the
      incidence of EPEC associated outbreaks has dramatically declined. The last major
      outbreak in the UK was reported in 1980. This paper reviews the recent advances
      in the field of pathogenesis of diarrhoea caused by EPEC and questions the need
      to screen routinely for EPEC by conventional serological methods used in clinical
      microbiology laboratories in the UK.

PMID- 1353509
TI  - The role of hospital infection control in the quality system of hospitals.
AB  - Like other highly specialized fields, quality systems have their own vocabulary
      which we must be familiar with; it has been internationally standardized. This
      standard should be adhered to in order to avoid unnecessary ambiguities and
      confusion, and to facilitate exchange of information between disciplines. We, in
      the infection control field, are quality pioneers in hospitals. We have, within
      our discipline, created quality systems and practised quality surveillance for
      decades. This must be recognized. Medical quality audits intended for comparisons
      between hospitals, services and wards require measurable quality criteria and
      comparable measures for the presence of all relevant patient-related risk
      factors. To specify quality within our field we need much more detailed
      information on the effect and cost of infection control practices, as well as the
      costs of the infections we intend to control. To progress one step further,
      patients or their representatives, politicians, need to express what monetary
      value should be put on health, namely freedom from infection and its
      consequences.

PMID- 1353510
TI  - Cost-effectiveness analysis of the use of chlorhexidine detergent in preoperative
      whole-body disinfection in wound infection prophylaxis.
AB  - A total of 3482 general surgical patients entered a trial in which they had a
      chlorhexidine or placebo detergent shower three times before elective clean wound
      or potentially contaminated surgery. Patients who showered with a chlorhexidine
      detergent (N = 1744) had a significant reduction in skin flora compared with
      those who showered with a placebo detergent (N = 1738). The majority of wound
      infections occurred outside hospital (312 outpatient infections vs. 201 inpatient
      infections). Wound infection rates were similar in the chlorhexidine and placebo
      groups (5.79% vs. 5.75% for inpatient infections and 8.54% vs. 9.38% for
      outpatient infections). The average hospital cost of both non-infected and
      infected patients was higher in the chlorhexidine group. The average cost of a
      non-infected chlorhexidine patient was 847.95 pounds as opposed to 804.60 pounds
      for a non-infected placebo patient, whilst the average cost of an infected
      patient was 1459.70 pounds (chlorhexidine) and 1414.22 pounds (placebo). A cross
      match comparison of patients undergoing vascular surgery revealed no statistical
      significance in the difference between the two experimental groups. Patients were
      matched for age, sex, type of operation and surgeon. We conclude that
      preoperative whole-body disinfection with a chlorhexidine detergent is not a cost
      effective treatment for reducing wound infection.

PMID- 1353511
TI  - Microbial growth and blockage of sub-floor drains in a renal dialysis centre: a
      problem highlighted.
AB  - The accumulation of microorganisms embedded in biofilm within the drainage
      pipework leading from individual dialysis monitors in a renal dialysis centre,
      represents a significant threat to the safe operation of the whole centre due to
      blockage of the pipes and overflow of waste water. Attempts to disperse the
      growth with chemicals and disinfectants have been unsuccessful. Only mechanical
      rodding has removed the deposit, and regrowth has occurred. Those planning new
      dialysis centres should ensure that effluent pipework is readily accessible with
      multiple rodding eyes and is made of material able to withstand rodding and
      chemicals.

PMID- 1353512
TI  - Staphylococcus aureus colonization of the newborn in a Darlington hospital.
AB  - Evidence from research studies suggests a relationship between neonatal infection
      with Staphylococcus aureus and the level of umbilical colonization. During a 3
      month prospective study (September-December 1990) the incidence and levels of S.
      aureus colonization were determined for all 370 live births in the Darlington
      Unit by taking swabs at 48 h and 8/9 days from the base of the umbilical cord.
      Infants were situated in one of four locations (The Special Care Unit, one of two
      wards or home) and the location at the time of swabbing was recorded. The overall
      percentages colonized at 48 h and 8/9 d were 68% and 65% respectively. Forty
      eight hours after delivery, 49% showed a high level of S. aureus colonization.
      Although the percentage of infants colonized with S. aureus was almost identical
      at each sampling, only 62% were culture-positive on both occasions. Between 48 h
      and 8/9 days, 12% (44) of infants developed S. aureus infections of whom 35
      showed heavy growth. Statistical analysis showed a significant relationship
      between levels of colonization at the two sampling times but no relationship
      between location and levels of colonization over the time period.

PMID- 1353513
TI  - Outbreak of Mycoplasma pneumoniae infection among hospital personnel studied by a
      nucleic acid hybridization test.
AB  - An outbreak of Mycoplasma pneumoniae (MP) infection occurred during the period
      March-May 1989 among the personnel of the Accident and Emergency Department of
      the Kuopio University Hospital, Kuopio, Finland. The index patient was a young
      male orderly, who fell ill with severe pneumonia. His tracheal mucus sample
      proved to be strongly positive for MP when tested by a commercial DNA-RNA
      hybridization test (Gen-Probe). After the index patient two additional staff
      members (an orderly and a nurse) fell ill with pneumonia and 66 others showed
      symptoms of upper respiratory infection or fever. The most frequent symptoms were
      a sore throat, a cough, rhinitis and headaches. All 97 employees of the
      department were tested for the presence of MP in April-May 1989 using throat
      swabs as test material. Forty-three (44%) were found to be positive for MP by the
      'Gen-Probe' test. Eight (19%) of the MP positive staff were completely
      asymptomatic. The MP positive staff were retested about 3 weeks later, whereupon
      40 (93%) had become negative. Most of the persons involved in this outbreak
      suffered only from mild respiratory symptoms, suggesting that MP outbreaks like
      the present one may easily pass unnoticed.

PMID- 1353514
TI  - A randomized study on the effect of bladder irrigation with povidone-iodine
      before removal of an indwelling catheter.
AB  - We have evaluated the effect of povidone-iodine (PVP-I) bladder irrigation prior
      to catheter removal on subsequent bacteriuria. Of 264 patients, 138 received PVP
      I irrigation and 126 were controls. Both groups were similar with respect to
      duration of catheterization and bacteriuria before removal of the catheter. Of
      497 cultures taken after catheter removal 99 (20%) were positive. This included
      52 of 233 in the control group (22%) and 47 of 264 in the study group (18%).
      Patients with positive cultures had a significantly longer period of
      catheterization. Our trial did not demonstrate that PVP-I bladder irrigation
      before catheter removal reduces subsequent bacteriuria.

PMID- 1353515
TI  - A study of 245 infected surgical wounds in Singapore.
AB  - The aims of the study were to correlate the laboratory detection rate of wound
      infections with the actual wound infection rate, and to analyse the bacteriology
      of these wounds to provide a rationale for antibiotic usage in prophylaxis and
      treatment of surgical wound infections. The wound infection rate in a general
      surgical unit was determined using the most comprehensive surveillance available
      to us and was correlated with the laboratory detection rate. A correlation
      coefficient of 0.8 was obtained, allowing a reasonable estimation of the actual
      wound infection rate from laboratory data. Review of the bacteriology of
      consecutive infected surgical wounds over a 4 year period in a university
      hospital, revealed that the commonest organisms cultured were Staphylococcus
      aureus, Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, enterococci
      and beta-haemolytic streptococci. Methicillin-resistant S. aureus (MRSA) caused
      50% of all staphylococcal wound infections. All MRSA isolates were sensitive to
      fusidic acid and vancomycin. All the non-MRSA isolates of S. aureus were
      sensitive to cephalexin. Some 89% of E. coli were sensitive to gentamicin, with
      93% and 100% sensitive to cefuroxime and ceftriaxone respectively. Klebsiella
      isolates have shown an increased resistance to aminoglycosides, with a new strain
      from one patient, isolated in 1990, resistant to penicillins, aminoglycosides and
      third generation cephalosporins. Pseudomonas spp., enterococci and beta
      haemolytic streptococci did not show a change in resistance patterns over the
      same time period.

PMID- 1353516
TI  - Teeth in the fracture line.
AB  - The department of maxillo-facial surgery in Cologne University has, for some 15
      years, routinely treated patients with mandibular fractures, in which a tooth
      lies in the fracture line, by means of Champy miniplates. A review of such cases
      was conducted to determine the viability of such teeth not electively extracted
      at the time of fracture reduction. It was found that only rarely did the
      "salvaged" tooth subsequently require extraction and we believe our results
      should encourage the clinician to attempt to retain "fracture line" teeth unless
      there is an absolute contraindication.

PMID- 1353517
TI  - Taxol, a microtubule-stabilizing antineoplastic agent, induces expression of
      tumor necrosis factor alpha and interleukin-1 in macrophages.
AB  - Taxol, a naturally occurring diterpene with antitumor activity, induces tubulin
      polymerization to generate abnormally stable and nonfunctional microtubules.
      Previously, we showed that taxol has lipopolysaccharide (LPS)-like effects on
      macrophages. As LPS is a potent inducer of macrophage cytokine production, we
      investigated whether a similar effect is exerted by taxol. In a dose-dependent
      manner, LPS-free taxol induced release of biologically active tumor necrosis
      factor alpha (TNF) by inflammatory murine macrophages. Taxol-induced production
      of TNF was inhibitable by interleukin-10. By Northern blot, taxol (10 and 1
      microM) induced TNF mRNA expression to an extent similar to LPS. Induction of TNF
      mRNA by 10 microM taxol was detectable at 45 min of stimulation, maximal at 90
      min, and evident for at least 8 h. The same low concentration of taxol also
      induced interleukin 1 (IL-1) alpha and beta mRNA expression. We conclude that
      taxol triggers macrophages for TNF and IL-1 production. These LPS-like effects of
      taxol might contribute to its antitumor activity.

PMID- 1353519
TI  - Nobel seminar: Molecular medicine--cell biology in disease. The mevalonate
      pathway--a link between cellular cholesterol homeostasis and growth regulation.

PMID- 1353518
TI  - Expression and distribution of CD11a/CD18 and CD54 during human T cell-B cell
      interactions.
AB  - Interactions between intercellular adhesion molecule 1 (ICAM-1, CD54) and
      leukocyte function-associated antigen 1 (LFA-1, CD11a/CD18) play a critical role
      in T cell-B cell collaboration. The current experiments were carried out to
      determine the expression and distribution of these adhesion molecules on human
      peripheral T cells and B cells during T cell-B cell collaboration. Resting CD4+ T
      cells were largely ICAM-1 negative, whereas immobilized anti-CD3 monoclonal
      antibody (mAb) rapidly induced ICAM-1 expression. By contrast, most B cells
      expressed ICAM-1 before activation, and further increases in density were noted
      with stimulation. Both B cells and CD4+ T cells expressed LFA-1 before
      activation, although the density on CD4+ T cells was considerably greater. A
      double staining method for electron microscopic analysis was developed that
      permitted analysis of the expression and distribution of ICAM-1 to be assessed
      during T cell-B cell collaboration. Under the experimental conditions examined, B
      cells showed a uniform distribution of ICAM-1. In contrast, ICAM-1 was highly
      mobile on the surface of CD4+ T cells. If the T cells were not fixed, staining,
      even at 4 degrees C, caused rapid redistribution of ICAM-1 into aggregates.
      However, by fixing cells before the staining procedures, the distribution of ICAM
      1 on CD4+ T cells could be accurately assessed. Most (85%) of the fixed activated
      CD4+ T cells showed a uniform distribution of ICAM-1. However, when activated
      CD4+ T cells were cocultured with B cells, redistribution of ICAM-1 on CD4+ T
      cells but not B cells occurred, such that the majority (85%) was found at or
      immediately adjacent to the point of attachment to the B cells. No redistribution
      of LFA-1 on either T cells or B cells was found. These findings suggest that
      rapid changes in density of ICAM-1 expression and the mobility of ICAM-1 on
      activated T cells may play a role in providing activation signals to B cells
      during T cell-B cell collaboration.

PMID- 1353520
TI  - Nobel seminar: Molecular medicine--cell biology in disease. Cancer and HIV: from
      viral genes to therapy?

PMID- 1353521
TI  - Complications of nephropathia epidemica: three cases.
AB  - Haemorrhagic fever with renal syndrome (HFRS) in Scandinavia is called
      nephropathia epidemica (NE), and is caused by the Puumala-virus, which belongs to
      the Hanta-virus genus. The clinical course of NE is mostly benign, complications
      are uncommon, and deaths are rarely observed. We report the cases of three
      patients who developed serious complications in the course of NE caused by the
      Puumala-virus. One patient died within 24 h after admission, another developed
      progressive neuromuscular dysfunction (Guillain-Barre syndrome) which required
      auxiliary ventilation for several weeks before a slow recovery, and a third
      patient developed empty sella syndrome with pituitary gland insufficiency. In the
      first two cases the diagnosis of NE was confirmed by a rapid avidity assay for
      IgG antibody against Puumala-virus. In the third case the clinical course, and
      demonstration of NE immunity 16 years later, suggested that NE might have caused
      the hypopituitarism. Some patients with NE caused by the Puumala-virus may
      require intensive-care treatment, and the development of late complications such
      as empty sella syndrome and hypopituitarism should be taken into consideration.

PMID- 1353522
TI  - Detection of serum IgM antibodies to glomerular basement membrane in two cases of
      nephropathia epidemica.
AB  - We report two serologically verified cases of nephropathia epidemica (NE) who
      developed high serum levels of non-Goodpasture IgM antibodies against glomerular
      basement membrane (anti GBM) in the acute phase of the disease. Moreover, in one
      of the patients a renal biopsy showed granular deposits of complement factor 3
      along the glomerular capillary walls. The possible pathogenic significance of
      these findings is discussed.

PMID- 1353524
TI  - Papers presented at the 38th Annual International Congress of the British
      Association of Paediatric Surgeons. Budapest, Hungary, July 24-26, 1991.

PMID- 1353523
TI  - Dysfunction of natural killer cells in human immunodeficiency virus-infected
      children with or without Pneumocystis carinii pneumonia.
AB  - The development of Pneumocystis carinii pneumonia (PCP) in human immunodeficiency
      virus (HIV)-infected children with normal T-cell numbers is contrary to previous
      experience with HIV-infected adults, in whom low CD4+ T-cell numbers predict
      susceptibility to PCP. To determine whether PCP in HIV-infected children reflects
      a qualitative T-cell or other immune defect, we studied four HIV-infected
      children who also had PCP and 10 others without PCP for T-cell and natural killer
      (NK) cell function. Most of the HIV-infected children had normal T-cell numbers
      for age, and all had CD4+ T-cell numbers greater than those predictive of PCP in
      HIV-infected adults. All HIV-infected children had normal T-cell function in
      vitro. The HIV-infected children as a whole had deficient NK cell cytolysis. We
      obtained a significant interactive effect of age by health status for NK cell
      function between patients and age-matched control subjects. All HIV-infected
      children with defective NK cell function failed to enhance their NK cell
      cytolysis when their mononuclear cells were stimulated with recombinant
      interferon alfa (r-IFN-alpha). This NK cell defect in HIV-infected children may
      facilitate the development of secondary infection.

PMID- 1353525
TI  - Management of renal hypertension in children with Takayasu's arteritis using
      renal autografting or allograft transplantation in selected circumstances and
      total lymphoid irradiation.
AB  - In a decade from 1980, 11 children aged 3 to 11 years presented with Takayasu's
      arteritis (TA). All were severely hypertensive. Operative correction was offered
      to 10 of 11 children presenting with renovascular hypertension (RVH) including
      cardiac failure alone in 1 and both renal and cardiac failure in 8, a result of
      TA involving renal arteries by stenosis or occlusion. Nine patients had renal
      autotransplantation to an heterotopic site in the pelvis. Seven of 12 kidneys
      were salvaged by autotransplant with relief of RVH. Renal artery stenosis was
      successfully corrected by this procedure in 5 patients. Autotransplantation
      failed in 4 patients, 1 of whom subsequently had a successful allograft
      transplant. One patient was treated primarily by cadaver allograft
      transplantation. One patient whose autotransplant failed had a functioning
      contralateral kidney and is well with controlled RVH. One patient died prior to
      any treatment. Patient survival improved with the use of total lymphoid
      irradiation in the most recent 7 patients.

PMID- 1353526
TI  - The natural course of cryptorchidism in rats and the efficacy of orchidopexy or
      orchidectomy in its treatment before and after puberty.
AB  - Both clinical and experimental evidence suggest that fertility is impaired in
      unilateral cryptorchidism. To investigate the effect of the undescended testis on
      the contralateral descended gonad, a new experimental model based on natural
      cryptorchidism in rats was designed. Seventy male Buffalo rats with an
      undescended right testis noted at the age of 30 days were used. Fifty healthy
      animals served as a controls. The natural course of cryptorchidism was
      investigated at the ages of 30, 90, and 180 days. The effects of orchiopexy and
      orchiectomy performed in cryptorchid animals before and after puberty were
      evaluated at the age of 180 days. Both nonoperated and operated animals were
      mated at the age of 150 days in order to estimate their fertility. The animals
      were killed at 30, 90, and 180 days of life and the testes were removed. In each
      excised testis testicular weight and seminiferous tubular diameters were measured
      and the maturity of the germinal epithelium was determined using the Johnsen
      testicular biopsy score. The experiment demonstrated reduced testicular weight
      and seminiferous tubular diameters in undescended testis already at 30 days and
      arrest of spermatogenesis at the spermatocytes stage at 90 and 180 days. There
      was no significant difference between contralateral descended testes and controls
      at the age of 30 and 90 days, but at 180 days the degenerative changes were
      identical with those in the cryptorchid testes. Cryptorchid rats were completely
      infertile. Both orchiopexy and orchiectomy prevented the damage to the
      contralateral testis. A significant improvement in size and spermatogenesis was
      recorded in most cases of the surgically descended testes.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1353527
TI  - Intrascrotal CGRP 8-37 causes a delay in testicular descent in mice.
AB  - The genitofemoral nerve is a key factor in the inguinoscrotal descent of the
      testis. The effect of androgens may be mediated via the central nervous system,
      which in turn secretes the neurotransmitter calcitonin gene-related peptide
      (CGRP) at the genitofemoral nerve endings, to cause testicular descent. The
      effect of endogenous CGRP was examined by weekly injections of a vehicle with or
      without synthetic antagonist (CGRP 8-37) into the developing scrotum of neonatal
      mice. The descent of the testis was delayed in the experimental group compared
      with the control group. At 2 weeks of age 43% of controls had descended testes
      compared with 0% of experimental animals. At 3 weeks of age 17% of experimentals
      still had undescended testes, whereas all testes were descended in controls. At 4
      weeks 3 testes remained undescended in the experimental group. It is concluded
      that the CGRP antagonist can retard testicular descent. This result is consistent
      with the hypothesis that CGRP is an important intermediary in testicular descent.

PMID- 1353528
TI  - Pheochromocytoma in children: 15 cases.
AB  - Pheochromocytoma is an uncommon tumor in childhood; nevertheless, 20% of all
      pheochromocytomas are found in the pediatric population. Fifteen children have
      been treated in our institution from 1962 to 1990. One percent of patients
      referred over the same period for investigation of high blood pressure were found
      to have a pheochromocytoma. The majority of patients have hypertension. It varies
      in intensity and is paroxysmal in about half the patients. Many pediatric cases
      of unilateral, bilateral, extra-adrenal, familial, and recurrent
      pheochromocytomas have been reported. We reviewed our 28 years experience with
      this tumor and concentrated on the diagnosis, the preoperative and operative
      management, and the occurrence of the multiple endocrine neoplasia syndromes.

PMID- 1353529
TI  - Neutrophil modulation by Actinobacillus actinomycetemcomitans. I. Chemotaxis,
      surface receptor expression and F-actin polymerization.
AB  - Localized juvenile periodontitis is an early onset periodontitis, usually
      localized to molars and incisors. Patients usually present with decreased
      chemotaxis of systemic neutrophils (PMNs) and infection with Actinobacillus
      actinomycetemcomitans. The pathogenic mechanisms involved have not been
      clarified. The purpose of this study was to determine if an extract of A.
      actinomycetemcomitans could induce changes in PMN chemotaxis similar to those
      reported in LJP patients. It was demonstrated that the bacterial extract was
      chemotactic for neutrophils. When neutrophils were pre-incubated with the
      bacterial extract, chemotaxis toward zymosan-activated serum, FMLP and the
      bacterial extract was inhibited in two different chemotaxis assays (Boyden
      chamber and under-agarose). Bacterial extract had no effect on random migration
      in either assay. Pre-incubation with the extract induced increased expression of
      CD11b/CD18 (Mac-1), Gp110, and FMLP receptors and increased F-actin
      polymerization following FMLP or PMA stimulation compared to cells not treated
      with the extract. Treatment of the bacterial extract with proteinase K or phenol
      extraction reversed the PMN chemotaxis inhibition activity, but increased
      significantly the random migration of PMNs. Heating the bacterial extract to 56
      degrees C had no effect on its activity. The component(s) in the bacterial
      extract that inhibits chemotaxis is therefore a protein(s), not sensitive to 56
      degrees C, and is not endotoxin. This study suggests that A.
      actinomycetemcomitans may contribute to the pathogenesis of localized juvenile
      periodontitis by inhibiting chemotaxis. Interference with chemotaxis by A.
      actinomycetemcomitans, however, occurs through a mechanism other than inhibition
      of actin assembly, reduction of CD11b/CD18 or Gp110 expression, or
      blockage/downregulation of FMLP receptors.

PMID- 1353530
TI  - Abstracts of the 4th International Symposium on Drug Analysis. Liege, Belgium, 5
      8 May 1992.

PMID- 1353531
TI  - Tissue expansion as an alternative to skin grafting for closure of skin deficits.
AB  - Recent advances in the technical aspects of tissue expanders for closure of skin
      deficits have led to an overall reduction in the high rate of complications
      typically associated with their usage. The authors provide a review of the recent
      refinements in the technique of the tissue expansion process. A discussion of
      current and future applications using this technique in the treatment of various
      lower extremity pathologies, including clubfoot, is presented. A case report on
      the use of a subcutaneous tissue expander for the treatment of a failed skin
      graft of the medial ankle is included.

PMID- 1353533
TI  - 7th European Conference on Cell and Molecular Biology of Ciliates. Toledo, Spain,
      September 2-6, 1991. Abstracts.

PMID- 1353532
TI  - Epidemiology of podiatric injuries in US Marine recruits undergoing basic
      training.
AB  - The authors determined the incidence of podiatric injuries that occurred during
      233,946 recruit days at risk among US Marine Corps recruits undergoing basic
      training at the Marine Corps Recruit Depot, San Diego, CA, between February 5 and
      April 25, 1990. Training-related initial injuries to the foot occurred at a rate
      of 3.0 new injuries per 1,000 recruit days. The highest specific rates of injury
      occurred with stress fractures to the foot (0.56 per 1,000 recruit days), ankle
      sprains (0.53 per 1,000 recruit days), and Achilles tendinitis (0.39 per 1,000
      recruit days).

PMID- 1353534
TI  - The aggregation of the 5' insulin gene polymorphism in insulin dependent (type I)
      diabetes mellitus families.
AB  - Population studies have suggested an increased frequency of small DNA insertions
      (class I alleles) 5' to the insulin gene in insulin dependent (type I) diabetes
      mellitus (IDDM). The present study examined this relationship within families.
      Forty-one families with at least one diabetic offspring were studied. Analysis of
      the insulin gene polymorphism was performed by digestion of DNA with Bg1I, SstI,
      RsaI, or PvuII and hybridisation with an insulin gene probe or polymorphic region
      specific probes. An increased frequency of class I alleles was found among the
      parents of diabetics (p = 0.02), as well as a trend towards increased frequency
      of parents homozygous for class I alleles and matings of two homozygous subjects.
      This increased homozygosity for class I alleles was present in non-diabetic sibs
      as well (p = 0.01). These results show that ascertainment through an offspring
      with IDDM selects for families with high frequencies of homozygosity for the
      class I allele and thus suggests that the insulin gene polymorphism is indeed
      providing part of the genetic predisposition to IDDM. When the major portion of
      genetic predisposition is provided by other genes (estimates are that HLA
      accounts for 30 to 70% in IDDM), identification of additional susceptibility
      genes becomes difficult. Even when formal linkage analysis is uninformative, our
      studies indicate that analysis for aggregation of specific alleles within
      families is a useful approach to this problem.

PMID- 1353535
TI  - Site specific screening for point mutations in ornithine transcarbamylase
      deficiency.
AB  - Ornithine transcarbamylase (OTC) deficiency is a frequent X linked disorder of
      the urea cycle which is responsible for lethal neonatal hyperammonaemia in males
      and for various clinical symptoms in heterozygous females. In order to improve
      the efficiency of our screening for mutant genotypes, we focused on molecular
      domains of functional or structural importance in the OTC gene, namely the
      carbamyl phosphate binding domain (encoded by the third exon) and the MspI
      restriction sites (CCGG) of the coding sequence (located in exons 2 and 7
      respectively), as they contain mutation hot spots (CpG doublets). Using this
      procedure, we were able to identify three new mutant genotypes in OTC deficient
      children including one nonsense mutation (E 87 K, G 50 ter, G 162 R). Since
      genetic counselling for OTC deficiency is frequently difficult, molecular
      screening directed towards specific sites of the coding sequence could allow
      rapid detection of mutant genotypes and help solve diagnostic problems,
      especially when carrier status cannot be clarified easily.

PMID- 1353536
TI  - Genetic variation at fibrinogen loci and plasma fibrinogen levels.
AB  - In view of the controversy regarding genetic variation at the fibrinogen loci and
      plasma fibrinogen levels, we have analysed DNA polymorphisms at the alpha (TaqI),
      beta (BclI and HaeIII), and gamma (KpnI/SacI) fibrinogen loci in 247 subjects
      whose plasma fibrinogen was determined by clotting and nephelometric assays.
      Strong linkage disequilibrium was found between the alpha/TaqI and
      gamma/KpnI/SacI markers and between the beta/BclI and beta/HaeIII markers. A
      lesser association was found between the alpha/TaqI and beta/BclI loci, beta/BclI
      and gamma/KpnI/SacI markers, alpha/TaqI and beta/HaeIII markers, and the
      gamma/KpnI/SacI and beta/HaeIII markers. This is consistent with the known
      physical order of these loci and suggests a relative excess of recombination in
      the alpha/gamma to beta interval. Plasma fibrinogen levels, by either assay
      method, when corrected or uncorrected for age, sex, and smoking habit, did not
      show any statistically significant associations with the four fibrinogen
      polymorphisms examined at the alpha, beta, and gamma fibrinogen loci either
      singly or when analysed as a haplotype.

PMID- 1353537
TI  - Researchers gain insights into suppressor gene function.

PMID- 1353538
TI  - Correlation of HER-2/neu amplification with expression and with other prognostic
      factors in 1103 breast cancers.

PMID- 1353539
TI  - Cytoskeletal elements regulate the distribution of nerve growth factor receptors
      in PC12 cells.
AB  - Nerve growth factor receptor (NGFR)-like immunoreactivity (IR) was studied in
      PC12 cells treated for 96 hr with NGF (40 ng/ml), using immunogold labeling and
      electron microscopic morphometric analysis. The cells were exposed to the anti
      NGFR antibody 192-IgG, followed by immunoglobulin (IgG) conjugated with colloidal
      gold. PC12 cells exhibited occasional gold label (positive NGFR-IR) on all
      surfaces. Cells treated with colcemid (0.05 micrograms/ml) or cytochalasin D (2
      micrograms/ml), which limit microtubule (MT) and microfilament (MF) formation,
      respectively, displayed an increased NGFR-IR in terms of gold labeling. NGFR-IR
      was also seen on taxol (0.85 micrograms/ml)-exposed cells, an agent that promotes
      MT assembly. Cells treated simultaneously with cytochalasin D and taxol had a
      dramatically augmented NGFR-IR on their surfaces, which exceeded levels obtained
      with either agent alone. Prominent NGFR-IR was localized frequently in coated
      endocytotic vesicles, in smooth endoplasmic reticulum, and in secondary
      multivesicular lysosomes, in both treated and untreated cells. The results
      suggest that a large number of NGFRs (positive NGFR-IR) in PC12 cells are cryptic
      and not available for ligand binding. Changes in cytoskeletal organization that
      may affect mobility of integral membrane proteins can modulate the distribution
      of NGFR-IR on neuronal surfaces.

PMID- 1353540
TI  - Buserelin treatment of cryptorchidism: a randomized, double-blind, placebo
      controlled study.
AB  - The objectives of the study were to determine whether a low dose of a luteinizing
      hormone-releasing hormone analogue (buserelin) has an effect on testicular
      descent, if buserelin affects germ cell maturation and epididymal development,
      the incidence of retractile testes in the controlled trials, and if the
      subsequent administration of human chorionic gonadotropin has any effect on the
      groups treated. The study was double blind, placebo controlled in which patients
      with cryptorchidism were assigned randomly into 3 groups: buserelin treatment
      (22), surgical treatment (18) or placebo control group (19). The 3 groups of
      patients were similar before treatment in regard to testicular position,
      chronological and bone age, height and weight, luteinizing hormone, follicle
      stimulating hormone, testosterone, penile size and the volume of the
      contralateral testis. Buserelin (20 micrograms). administered daily in a nasal
      spray significantly induced testicular descent compared to the group treated with
      a placebo (p less than 0.01). A normal epididymis was found more often in boys
      with successful descent (p less than 0.003). Boys treated with buserelin had the
      highest number and the best maturation index of the germ cells; human chorionic
      gonadotropin influenced the descent in both groups but it was more efficacious
      when it was administered after treatment with buserelin, although it had no
      additional effect on germ cell maturation. None of the boys had retractile
      testes. Buserelin was capable of inducing testicular descent in addition to
      increasing simultaneously the number of germ cells and provoking further
      development of the epididymis.

PMID- 1353541
TI  - Is a testis located at the superficial inguinal pouch (Denis Browne pouch)
      comparable to a true cryptorchid testis?
AB  - In a clinical study 96 prepubertal boys with 100 testes located in the
      superficial inguinal pouch underwent routine orchiopexy. Of 65 patients 45 (69%)
      who had received hormonal treatment before the surgical procedure had a closed
      processus vaginalis compared with only 11 of 35 (31%) who had not (p less than
      0.0002). A normal epididymis was also present significantly more often in those
      patients receiving hormonal treatment than in those who did not (p less than
      0.039). While those testes located in the superficial inguinal pouch had
      significantly better histology and a greater number of germ cells than those
      located in a high inguinal or abdominal position (p less than 0.01), the number
      of germ cells per tubule was nonetheless lower than that seen in the normal
      controls (p less than 0.01). In conclusion, a testis located at the superficial
      inguinal pouch behaves as a true cryptorchid testis. Furthermore, hormonal
      treatment before surgery has a significant effect on epididymal development and
      closure of the processus vaginalis.

PMID- 1353542
TI  - Epididymal anomalies associated with hydrocele/hernia and cryptorchidism:
      implications regarding testicular descent.
AB  - Controversy exists regarding the role of the epididymis in testicular descent, as
      epididymal abnormalities have been reported in 36 to 79% of boys with an
      undescended testis. Although most undescended testes are associated with a patent
      processus vaginalis, the incidence of epididymal abnormalities in descended
      testes with a patent processus has not been reported. Epididymal morphology was
      examined in 81 boys with a hydrocele/hernia without cryptorchidism (90 testes)
      and 100 children undergoing orchiopexy (115 testes). Boys with an intra-abdominal
      undescended testis were excluded. Among 48 boys with a hydrocele/hernia 24 (50%)
      had an epididymal abnormality if the processus was patent and communicated with
      the testis (complete hernia), compared to 4 of 42 patients (10%) if there was not
      a communication with the testis (p less than 0.01). Among the 96 children with an
      undescended testis 68 (71%) had an epididymal abnormality if there was a patent
      processus, compared to 3 of 19 boys (16%) without a patent processus (p less than
      0.01). These data suggest that most epididymal abnormalities probably do not
      contribute to testicular maldescent.

PMID- 1353543
TI  - An absent testis is associated with contralateral testicular hypertrophy.
AB  - Surgical exploration was done in 109 boys ages birth through 9 years with
      unilateral impalpable testes by physical examination under anesthesia. Of the
      patients 51 (47%) had an absent testis and 58 had intra-abdominal testes. At open
      biopsy of the contralateral descended testis the 3 dimensions of the exposed
      testis were recorded and testicular volume was calculated. The mean volume of the
      contralateral descended testes of boys with an absent testis was greater than
      that of boys with intra-abdominal testes at all ages. The differences were
      significant (p = 0.0019 to 0.0117) from birth through year 4 but not from years 5
      through 9. However, the standard deviations ranged from 27 to 74% of the means,
      and there was broad overlap of the volumes of the 2 groups. These findings
      indicate that, although the volume of the contralateral descended testis of boys
      with an absent testis is significantly greater than that of boys with intra
      abdominal testes, the volume of the contralateral descended testis is not a
      reliable criterion for differentiating an absent testis from an intra-abdominal
      testis in a boy with a unilateral impalpable testis. Surgical exploration
      continues to be the method of choice for making the diagnosis of an absent
      testis.

PMID- 1353544
TI  - The management of the impalpable testis by surgery alone.
AB  - We evaluated 68 prepubertal boys with 84 impalpable testes who were operated upon
      without using any other diagnostic maneuvers. Of the testes 18 (22%) were absent
      (anorchism or 'vanished') and 38 (45%) could be placed in a scrotal position with
      standard orchiopexy. A staged, Fowler-Stephens or microvascular procedure was
      required for 28 testes (33%), involving orchiectomy in 2 cases, and succeeded in
      a scrotal position for another 24 testes. In 1 boy 2 testes were fixed outside
      the inguinal canal. Reexamination after 3 to 9 years showed that 42 of 55
      operated testes (76%) were in scrotal position without atrophy, 10 had atrophied
      and 3 were removed at the second stage operation. We conclude that an exclusive
      surgical approach has the advantage of providing diagnosis and therapy, and,
      therefore, it is an effective method.

PMID- 1353545
TI  - The value of laparoscopy for 106 impalpable testes relative to clinical
      presentation.
AB  - Laparoscopy was done in 104 consecutive patients with 106 impalpable testes.
      Three clinical presentations were identified and the value of laparoscopy in each
      was analyzed. 1) For unilateral impalpable and contralateral normal testes
      laparoscopic identification of testicular absence was made in 27% of the cases
      and intra-abdominal testes were found in 16%. Therefore, laparoscopy was of value
      in 43% of the cases. 2) For bilateral undescended testes (1 or both impalpable)
      laparoscopy was diagnostic in 75% of the cases (17% had blind-ending spermatic
      vessels above the internal ring and 58% had intra-abdominal testes). 3) For
      patients with previous negative inguinal exploration laparoscopic diagnosis was
      made in 100%.

PMID- 1353546
TI  - Laparoscopy for nonpalpable testes in childhood: is inguinal exploration also
      necessary when vas and vessels exit the inguinal ring?
AB  - Laparoscopy has proved to be a safe method for determining the status for
      nonpalpable testes. In a combined series 52 boys with 57 nonpalpable testes were
      evaluated laparoscopically. Of the 57 nonpalpable testes 26 were located above
      the internal inguinal ring (abdominal), 4 were found more distally, and blind
      ending vas and vessels terminated in the abdomen in 3, and beyond the internal
      ring (vanished testes) in 24. Of 29 abdominal testes primary orchiopexy was
      performed in 15, 4 were removed, the vessels were transected (Fowler-Stephens) in
      5, stage 1 of staged repairs was done in 2, distinct laparoscopic evidence of
      blind-ending vessels and vas obviated further surgery in 2, and testis was not
      identified either laparoscopically or by abdominal exploration. Finally, inguinal
      exploration in 28 children in whom vas and vessels were found to exit the
      internal ring resulted in localization of 4 testes that were brought into the
      scrotum. Removal of 23 testicular nubbins and their evaluation histologically
      resulted in identification of viable tubular structures in 3. We recommend
      inguinal exploration in all children who on laparoscopy are found to have vas and
      vessels exit the internal ring, and removal of testicular nubbins.

PMID- 1353547
TI  - Stimulation of Na absorption by the antiasthmatic kampo drug Saiboku-to in
      cultured airway epithelium.
AB  - To study the effect of the Kampo drug Saiboku-to (TJ-96) on ion transport
      function of airway epithelial cells, we studied bioelectric properties of
      cultured tracheal epithelium from dogs under short-circuit conditions in vitro.
      Addition of TJ-96 (1 mg/ml) to the mucosal solution of the Ussing chamber
      increased the epithelial short-circuit current (SCC) from 6.5 +/- 0.7 to 11.4 +/-
      1.6 microA/cm2 (P less than 0.001). This effect was dose-dependent, with the
      maximal increase from the baseline value and the concentration required to
      produce a half-maximal effect (EC50) being 70.5 +/- 12.6% (P less than 0.001) and
      3 micrograms/ml, respectively; and there were corresponding increases in
      transepithelial potential difference and cell conductance. Submucosal addition of
      TJ-96 likewise increased SCC, although the magnitude of the response was smaller
      as compared with the response to the mucosal addition. The TJ-96-induced increase
      in SCC was not affected by diphenylamine-2-carboxylate or furosemide but
      abolished by amiloride. Intracellular cyclic AMP levels were dose-dependently
      increased by TJ-96. These results indicate that TJ-96 may selectively stimulate
      Na absorption across the tracheal epithelium, probably through intracellular
      accumulation of cyclic AMP.

PMID- 1353549
TI  - Tissue distribution of methylenedioxymethamphetamine.
AB  - Two cases of death involving methylenedioxymethamphetamine (MDMA) are reported;
      one case is a fatal acute overdose and the other is a drug-related death. The
      tissue distribution of MDMA is reported in both cases.

PMID- 1353548
TI  - Solid-phase extraction and GC/MS confirmation of barbiturates from human urine.
AB  - A highly selective and sensitive procedure has been developed for isolating and
      identifying barbiturates in human urine. With a new disposable bonded silica gel
      solid-phase extraction (SPE) column and hexobarbital as an internal standard
      (IS), amobarbital, butabarbital, pentobarbital, phenobarbital, secobarbital, and
      methaqualone were selectively isolated from endogenous urine components.
      Capillary gas chromatography/ion trap mass spectrometry (GC/MS) analysis of the
      extracts generated a full mass spectrum for the detection, identification, and
      quantitation of barbiturates. Linear quantitative response curves for the drugs
      have been generated over a concentration range of 20-500 ng/mL. Overall
      extraction efficiencies for drugs averaged greater than 90%, and the quantitative
      response curves exhibited correlation coefficients of 0.996 to 0.999.

PMID- 1353550
TI  - Specific point mutations that activate v-abl are not found in Philadelphia
      negative chronic myeloid leukaemia, Philadelphia-negative acute lymphoblastic
      leukaemia or blast transformation of chronic myeloid leukaemia.
AB  - The involvement of the BCRlABL fusion gene in patients with Philadelphia (Ph)
      chromosome positive chronic myeloid leukaemia (CML) and acute lymphoblastic
      leukaemia (ALL) is well characterised, but the molecular events underlying the
      cases of Ph-negative CML and ALL that lack BCR gene involvement and those that
      cause transformation of Ph-positive CML are unknown. The murine ABL gene can be
      activated by genetic events that do not involve the BCR gene, including the
      introduction of two specific point mutations in exons VII and XI respectively, as
      found in the homologous sequence of the v-abl oncogene. We therefore sought
      evidence for analogous point mutations in the ABL gene in patients with Ph
      negative, BCR-negative CML (n = 25), Ph-negative ALL (n = 18) and in Ph-positive
      CML in transformation (n = 28). We used restriction fragment length polymorphism
      and single strand conformational polymorphism techniques to analyse DNA amplified
      fragments of selected ABL coding regions from leukaemia cells. We identified only
      normal wild-type DNA sequences. The absence of these transforming point mutations
      does not exclude the possibility that the ABL gene in such patients could be
      activated by other means.

PMID- 1353551
TI  - XbaI RFLP of ETS-1 oncogene in chronic B-cell leukaemia.
AB  - The influence of a polymorphic variant of the ETS-1 oncogene on the
      predisposition to develop chronic B-cell leukemia (CLL) was investigated. A total
      of 59 patients with CLL and 59 controls were examined for the frequency of an
      XbaI restriction fragment length polymorphism RFLP of the ETS-1 oncogene which
      has been reported to occur more frequently in patients with hematological
      malignancies than in normal controls. We found no significant difference in the
      allele frequency between the CLL patients and the normal controls. These data
      suggest that the presence of the XbaI RFLP is not associated with CLL.

PMID- 1353552
TI  - Remission induction of acute promyelocytic leukemia by all-trans-retinoic acid:
      molecular evidence of restoration of normal hematopoiesis after differentiation
      and subsequent extinction of leukemic clone.
AB  - Sequential molecular and cellular changes during remission induction were
      investigated in a case of acute promyelocytic leukemia (APL) treated with all
      trans-retinoic acid (ATRA). By means of clonality analysis, the assessment of the
      retinoic acid receptor alpha gene alterations, as well as conventional cytologic
      studies, it was demonstrated that remission induction of APL by ATRA proceeds in
      two steps: first, the differentiation of the leukemic clone to mature
      granulocytes and its subsequent extinction; second, proliferation/differentiation
      of the residual normal clones to restore polyclonal hematopoiesis.

PMID- 1353553
TI  - Maternal inheritance of atopic IgE responsiveness on chromosome 11q.
AB  - Atopy is a common familial state underlying allergic asthma and rhinitis. Lately,
      we have assigned a gene for atopy to chromosome 11q by linkage to the marker
      D11S97. Since previous studies have suggested that the risk of atopy is higher
      for children of atopic mothers than for those of atopic fathers, we sought
      differences between maternal and paternal patterns of transmission at the 11q13
      locus among pairs of siblings in families affected by atopy. When we defined
      atopy as the presence of a positive skinprick test (greater than or equal to 2
      mm) to any of a panel of common allergens, a higher than normal concentration of
      total serum IgE, or a positive radioallergosorbent test for a specific IgE, we
      found that 125 (62%) of the sibling-pairs affected by atopy shared the maternal
      11q13 allele and 78 (38%) did not. This distribution differs significantly from
      the expected 50/50 distribution (p = 0.001). Of paternally derived alleles, 83
      (46%) were shared and 96 (54%) were not (not significantly different from 50/50).
      The result was similar whatever definition of atopy was used and with other
      genetic markers on 11q. These findings show that transmission of atopy at the
      chromosome 11q locus is detectable only through the maternal line. The pattern of
      inheritance is consistent either with paternal genomic imprinting or with
      maternal modification of developing immune responses.

PMID- 1353554
TI  - Toxicity and deaths from 3,4-methylenedioxymethamphetamine ("ecstasy")
AB  - The risk of adverse reactions to 3,4-methylenedioxymethamphetamine (MDMA), more
      commonly known as "ecstasy", is now widely known in both the USA and UK, but the
      patterns of illness remain varied. We report our experience during 1990 and 1991.
      There has been a recent increase in cases of severe toxicity following
      recreational misuse of small amounts of MDMA. Among 7 fatalities, the pattern of
      toxicity included fulminant hyperthermia, convulsions, disseminated intravascular
      coagulation, rhabdomyolysis, and acute renal failure. Until now, there have been
      few reports of this type of toxicity from MDMA, which may be related both to the
      potential of the drug to alter thermoregulation and to the circumstances of
      misuse. In addition, we have monitored 7 cases of hepatotoxicity and suspect that
      the frequency of this complication is increasing; a history of MDMA misuse should
      be sought in young people presenting with unexplained jaundice or hepatomegaly.
      We also describe 5 subjects involved in road traffic accidents in whom MDMA was
      identified. Misuse of MDMA can have severe acute toxic effects; few data are
      available concerning long-term morbidity, and this deserves close monitoring in
      future.

PMID- 1353555
TI  - Influence of cross-sex transmission on measles mortality in rural Senegal.
AB  - Previous studies of measles mortality in West Africa have shown a significantly
      higher case-fatality rate (CFR) among girls than among boys. This study aimed to
      find out whether the male/female difference in CFR is related to different risks
      for boys and girls of being infected as secondary rather than index cases and of
      transmission from someone of the same or the opposite sex. The study was
      conducted in Niakhar, a rural area of Senegal (population 24,000). All cases of
      measles reported between March, 1983, and December, 1986, were investigated to
      determine source of infection and pattern of transmission. For each case, the
      closest source of infection was judged the most likely. Death was attributed to
      measles if it occurred within 6 weeks of the onset of rash. Girls had a higher
      measles CFR than boys (53 deaths/722 cases [7.3%] vs 45/778 [5.8%]); the relative
      risk of death was 1.30 (95% confidence interval [CI] 0.89-1.90). Secondary cases
      infected by a child of the opposite sex had a 2.44 (1.48-4.02) times higher risk
      of death than did secondary cases infected by a child of the same sex. The risk
      of cross-sex transmission of infection was significantly greater for female than
      for male secondary cases (1.26 [1.09-1.47]). When this difference in risk of
      exposure to infection from the opposite sex was taken into account, the
      difference in risk of death between girls and boys disappeared (1.06 [0.66
      1.69]). Within families, the CFR was higher in huts with 1 boy and 1 girl
      affected than in huts of either 2 boys or 2 girls affected (relative risk 2.16
      [0.99-4.70]). Measles infection contracted from a person of the opposite sex is
      more severe. Variation in exposure may be an important determinant of sex
      differences in case fatality.

PMID- 1353556
TI  - Chromosome status of untransferred (spare) embryos and probability of pregnancy
      after in-vitro fertilisation.
AB  - Many spontaneous abortions are associated with chromosomal abnormality of the
      fetus. In in-vitro fertilisation (IVF) the chromosome status of untransferred
      ("spare") embryos and subsequent fate (pregnancy or not) of the transferred
      sibling embryos might be related. Since the spare and transferred embryos of a
      patient's cycle genetically are full siblings, the inherited chromosomal
      abnormalities in spare embryos have a 50% probability of also appearing in
      transferred embryos. We have tested whether chromosome analysis of spare embryos
      has predictive power for transferred embryos. 48 couples with a total of 437
      embryos were selected because their spare embryos (1-4 per couple; 76 total) were
      successfully analysed for chromosome status. 16 patients became pregnant. These
      women produced a higher proportion of chromosomally normal spare embryos (9/24;
      37.5%) than those who did not achieve pregnancy (1/52; 1.9%). The proportion of
      patients who had only normal embryos was significantly higher (p = 0.012) in the
      pregnant group than in the non-pregnant group, and the proportion of patients who
      had only abnormal embryos was significantly higher (p = 0.001) in the non
      pregnant group. Patients with preclinical and clinical pregnancy losses had only
      chromosomally abnormal spare embryos; by contrast, 50% of spare embryos from
      patients with ectopic pregnancies were normal. The proportion of spare embryos
      that were normal (13%, 10/76), was similar to the livebirth rate of 11% per
      transferred embryo (19 infants from 171 transferred embryos). These results
      suggest that chromosome analysis of spare embryos may have predictive value for
      their transferred sibling embryos. We conclude that improving detection of
      chromosomally normal embryos for transfer should improve the success rate in IVF.

PMID- 1353557
TI  - Magnetic resonance imaging of anal fistulae.
AB  - Success of surgery for an anal fistula depends on accurate assessment of the
      fistula; however, such assessment is technically difficult. We have done a
      prospective study that determined the accuracy of magnetic resonance imaging
      (MRI) in demonstrating the course of fistulae, by comparing MRI scan
      interpretations with subsequent operative findings. 16 patients (mean [range] age
      42 [24-66] years) had MRI followed by surgery within a mean of 22 (1-101) days.
      MRI scan interpretations agreed precisely with independently documented operative
      findings in 14 of 16 patients. MRI is an accurate method of delineating anal
      fistulae, and should be considered for patients with difficult fistulae that
      recur despite skilled attention because it demonstrates abnormalities that might
      otherwise be missed.

PMID- 1353558
TI  - Risk of pneumonia in patients previously treated in hospital for pneumonia.
AB  - Although elderly patients who are admitted to hospital for any disease have a
      higher risk of pneumonia subsequently, whether those treated in hospital for
      pneumonia are at even greater risk is unknown. Therefore we retrospectively
      assessed morbidity and mortality due to pneumonia after discharge in 573
      consecutive patients admitted to hospital for pneumonia, gastrointestinal
      infection, renal infection, or erysipelas. Average follow-up was 34 months. The
      incidence rate for pneumonia was 5.45 times higher in the group of patients
      discharged after pneumonia than in the other groups combined (95% confidence
      interval 2.89-10.26; p less than 0.001), and this group also had more deaths due
      to pneumonia (p = 0.06). For patients 50 years or older Streptococcus pneumoniae
      is the main cause of pneumonia. Pneumococcal vaccination after hospital treatment
      for an episode of pneumonia might be a cost-effective means of preventing disease
      in this group.

PMID- 1353560
TI  - The cancer epidemic: fact or misinterpretation?

PMID- 1353559
TI  - Effect of indomethacin plus ranitidine in advanced melanoma patients on high-dose
      interleukin-2.
AB  - Preclinical models of advanced melanoma have shown that chronic indomethacin
      therapy combined with interleukin 2 (IL-2) can eradicate experimental metastases.
      A phase II trial was done in patients with advanced melanoma. Indomethacin and
      ranitidine were begun at least one week before IL-2. Of the objective responses
      in 3 patients, 2 were achieved on ranitidine and indomethacin alone, before start
      of IL-2. Indomethacin and ranitidine may be responsible for some responses in
      melanoma patients previously attributed to IL-2.

PMID- 1353561
TI  - Penicillin, ceftazidime, and the epilepsies.

PMID- 1353562
TI  - Selection for audit.

PMID- 1353563
TI  - Alpha 1-antitrypsin, Z, and the liver.

PMID- 1353564
TI  - Muscling in on clenbuterol.

PMID- 1353565
TI  - Pathophysiology of obesity.

PMID- 1353566
TI  - Treatment of obesity.

PMID- 1353567
TI  - Look at the patient, not the notes.

PMID- 1353568
TI  - A fifty-year follow-up of congenital rubella.
AB  - 50 patients with congenital rubella, born in 1939-43, were reviewed in 1967. Here
      we report their outcome in 1991. Since 1967, there have been 7 deaths (3
      cardiovascular, 3 malignant disease, 1 AIDS). 40 had full clinical assessment.
      The prevalence of diabetes mellitus is similar to that in 1967: 4 of the 5
      reported diabetic then, remain so, and there is 1 new case. 1 subject has
      malignant melanoma and 3 have died from cancer. Although the incidence of
      malignant disease is not increased, the death rate is (standardised mortality
      rate 6.0, 95% CI 1.24-17.57). Longer follow-up will be required to confirm this
      observation.

PMID- 1353569
TI  - AIDS without HIV?

PMID- 1353570
TI  - Consulting about children with HIV.

PMID- 1353571
TI  - Prophylactic vancomycin to prevent staphylococcal septicaemia in very-low-birth
      weight infants.

PMID- 1353572
TI  - Inhalation injury with a new infant safety device in a child.

PMID- 1353573
TI  - Interferon alfa for linear IgA bullous dermatosis.

PMID- 1353574
TI  - Response of cyclophosphamide-resistant Wegener's granulomatosis to etoposide.

PMID- 1353575
TI  - Magnesium and chronic fatigue syndrome.

PMID- 1353576
TI  - Detection of long-lasting antibody to hepatitis E virus in a US traveller to
      Pakistan.

PMID- 1353577
TI  - High HCV prevalence in Egyptian blood donors.

PMID- 1353578
TI  - Myocarditis caused by Chlamydia pneumoniae (TWAR) and sudden unexpected death in
      a Swedish elite orienteer.

PMID- 1353579
TI  - "Stress hormones" and bungee-jumping.

PMID- 1353580
TI  - Desferrioxamine and pulmonary injury.

PMID- 1353581
TI  - First-trimester transabdominal fetoscopy.

PMID- 1353582
TI  - Autoimmune Addison's disease and 21-hydroxylase.

PMID- 1353583
TI  - Autoantibodies in Down's syndrome.

PMID- 1353584
TI  - Vigabatrin for startle-disease with altered cerebrospinal-fluid free gamma
      aminobutyric acid.

PMID- 1353585
TI  - Changes of allele-specific expression of apo(a) gene in infants during first year
      of life.

PMID- 1353586
TI  - Education of patients about chronic obstructive pulmonary disease.

PMID- 1353587
TI  - How Israel tackled homoeopathy.

PMID- 1353588
TI  - Zinc metabolism in hypothyroidism.

PMID- 1353590
TI  - False sonographic appearance of endometrial neoplasia in postmenopausal women
      treated with tamoxifen.

PMID- 1353589
TI  - Combination chemotherapy for myelomatosis.

PMID- 1353591
TI  - Measurement of mood and hypnosis.

PMID- 1353592
TI  - How safe is BCG vaccination in children born to HIV-positive mothers?

PMID- 1353593
TI  - Contribution of maternal viral load to HIV-1 transmission.

PMID- 1353594
TI  - Bone minerals and levothyroxine.

PMID- 1353595
TI  - Bone minerals and levothyroxine.

PMID- 1353596
TI  - Bone minerals and levothyroxine.

PMID- 1353597
TI  - Bone minerals and levothyroxine.

PMID- 1353598
TI  - Leukaemia after iodine-131 exposure.

PMID- 1353599
TI  - Antibiotic resistance in pneumococcal meningitis.

PMID- 1353600
TI  - Antibiotic resistance to pneumococcal meningitis.

PMID- 1353601
TI  - Antibiotic resistance to pneumococcal meningitis.

PMID- 1353602
TI  - Variations in the expression of pili: the effect on adherence of Neisseria
      meningitidis to human epithelial and endothelial cells.
AB  - The effect of variations in Neisseria meningitidis pili on bacterial interactions
      with three epithelial cell lines as well as human umbilical vein endothelial
      cells was studied using a panel of seven strains expressing Class I or Class II
      pili. Comparison of adherence of piliated and pilus-deficient variants of each
      strain to epithelial cells suggested that Class I pili may mediate bacterial
      adherence with all three epithelial cell lines. In contrast, Class II pili of the
      strains used did not increase bacterial adherence to Hep-2 larynx carcinoma
      cells, although an increase in adherence to Chang conjunctival and A549 lung
      carcinoma epithelial cells was observed in the Class II pili-expressing strains.
      In addition to these interclass functional variations, differences in adherence
      to epithelial cells were also observed among Class I and Class II strains.
      Functionally different pilin variants of one Class I strain, MC58, were obtained
      by single colony isolation. One piliated variant was identified which had
      concurrently lost the ability to adhere to both Chang and Hep-2 cells ('non
      adherent' phenotype; adherence of less than 2 bacteria per cell). In addition,
      several adherent pilin variants were isolated from non-adherent Pil- and Pil+
      bacteria by selection on Chang cells (adherence of 10-25 bacteria per cell). In
      contrast to epithelial cells, all variant pili, whether of Class I or Class II,
      adhered to endothelial cells in substantially larger numbers (greater than 50
      bacteria per cell) and therefore implied the existence of distinct mechanisms in
      pilus-facilitated interactions of N. meningitidis with endothelial and epithelial
      cells.

PMID- 1353603
TI  - Psychoactive drug prescribing in the Tasmanian community.
AB  - OBJECTIVE: To gather data on the prescribing of psychoactive drugs
      (benzodiazepines, antidepressants and antipsychotics) using a network of
      Tasmanian community pharmacies. DESIGN SETTING AND PARTICIPANTS: The prescribing
      of psychoactive drugs in the community was studied during 1989 using data
      retrospectively obtained from computerised dispensing systems in 11 community
      pharmacies in Tasmania. The data collection procedure included all prescriptions
      dispensed in the pharmacies, irrespective of supply under the Pharmaceutical
      Benefits Scheme, the Repatriation Pharmaceutical Benefits Scheme or as a private
      prescription. MAIN OUTCOME MEASURES: Results of the pooled data were quantified
      by both the number of prescriptions and the defined daily doses (DDDs) dispensed
      for the psychoactive drugs. RESULTS: When extrapolated to the population of
      Tasmania, the estimated annual prescribing rates for the benzodiazepines,
      antidepressants and antipsychotics (including lithium) were 853.3, 316.2 and 54.8
      prescriptions per 1000 persons, respectively. Prescriptions for the psychoactive
      drugs accounted for 13.2% of all prescriptions dispensed. In terms of DDDs, the
      estimated prescribing rates for the total Tasmanian population for the
      benzodiazepines, antidepressants and antipsychotics were 47.8, 12.5 and 2.1 DDDs
      per 1000 persons per day, respectively. The rate of benzodiazepine prescribing
      appeared to be high in comparison with the limited Australian data available. The
      relative prescribing rates of the long acting benzodiazepine hypnotics,
      flunitrazepam and nitrazepam, were also disturbingly high. CONCLUSIONS: This
      study has demonstrated the potential value of comprehensive
      pharmacoepidemiological data obtained from a network of community pharmacists and
      will form the basis for future studies using an expanded collection procedure.

PMID- 1353605
TI  - Absence of markers for HTLV infection among australian injecting drug users.

PMID- 1353604
TI  - Medical management of pituitary tumours.

PMID- 1353606
TI  - Update: CD4+ T-lymphocytopenia in persons without evident HIV infection--United
      States.
AB  - On July 31, 1992, CDC reported five cases of CD4+ T-lymphocytopenia in persons
      without evident human immunodeficiency virus (HIV) infection in the United
      States. As of August 5, 1992, CDC has received reports of nine additional persons
      with similar clinical presentations. All persons who have been reported to CDC
      meet the three criteria for CD4+ T-lymphocytopenia without evident HIV infection.
      Another 21 persons suspected to have this condition have been described, 10 of
      whom reside in the United States. This report summarizes the 14 cases reported to
      CDC and provides information on the national surveillance system established to
      determine the prevalence and distribution of this condition.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1353607
TI  - A controlled trial comparing continued zidovudine with didanosine in human
      immunodeficiency virus infection. The NIAID AIDS Clinical Trials Group.
AB  - BACKGROUND: Although zidovudine is effective in patients with human
      immunodeficiency virus (HIV) infection, its efficacy may decline with prolonged
      use. Didanosine is another inhibitor of HIV reverse transcriptase. We evaluated
      the effectiveness of changing anti-HIV treatment from zidovudine to didanosine.
      METHODS: This multicenter, double-blind study involved 913 patients who had
      tolerated zidovudine for at least 16 weeks. The patients had the acquired
      immunodeficiency syndrome (AIDS), AIDS-related complex with less than or equal to
      300 CD4 cells per cubic milliliter, or asymptomatic HIV infection with less than
      or equal to 200 CD4 cells per cubic milliliter. They were randomly assigned to
      receive 600 mg per day of zidovudine, 750 mg per day of didanosine, or 500 mg per
      day of didanosine. RESULTS: There were significantly fewer new AIDS-defining
      events and deaths among the 298 subjects assigned to 500 mg per day of didanosine
      than among the subjects who continued to receive zidovudine (relative risk, 1.39;
      95 percent confidence interval, 1.06 to 1.82; P = 0.015). With 750 mg of
      didanosine, there was no clear benefit over zidovudine (relative risk, 1.10; 95
      percent confidence interval, 0.86 to 1.42). The efficacy of didanosine was
      unrelated to the duration of previous zidovudine treatment. In the two didanosine
      groups, there were improvements in the number of CD4 cells (P less than 0.001 for
      both groups) and in p24 antigen levels (P = 0.03 in the 500-mg group; P = 0.005
      in the 750-mg group), as compared with the zidovudine group. CONCLUSIONS:
      Changing treatment from zidovudine to 500 mg per day of didanosine appears to
      slow the progression of HIV disease.

PMID- 1353608
TI  - Deformed autoregulatory element from Drosophila functions in a conserved manner
      in transgenic mice.
AB  - The striking similarities in the structure, organization and anterior-posterior
      expression patterns between the murine Hox gene system and the Drosophila
      homeotic gene complexes, called HOM-C (ref. 3), may point to highly conserved
      mechanisms for specifying positional identities (reviewed in ref. 4). Strong
      support for this concept lies in the observation of conserved colinearity between
      the genomic order of the Hox/HOM genes and their unique successive expression
      domains along the anterior-posterior axes of both mouse and fly embryos. These
      unique and precise expression patterns appear to be facilitated by multiple cis
      regulatory elements (reviewed in ref. 5). One of the few elements characterized
      in detail is the autoregulatory enhancer of the homeotic gene Deformed (Dfd),
      which supports expression in subregions of posterior head segments of Drosophila
      embryos. Here we present evidence that this enhancer is capable of conferring
      reporter gene expression to a discrete subregion of the hindbrain in transgenic
      mouse embryos. Remarkably, this anterior-posterior subregion lies within the
      common anterior expression domain of the Dfd cognate Hox genes in the postotic
      hindbrain. Our results indicate that the Dfd autoregulatory enhancer is part of a
      highly conserved mechanism for establishing region-specific gene expression along
      the anterior-posterior axis of the embryo.

PMID- 1353609
TI  - A human HOX4B regulatory element provides head-specific expression in Drosophila
      embryos.
AB  - Like other homeobox genes of the Antennapedia and bithorax complexes
      (collectively called the HOM complex), the Drosophila Deformed (Dfd) gene has
      structural homologues in the Hox/HOX complexes of mouse and humans, one of which
      is human HOX4B (refs 3, 4). Previous experiments indicated that HOX4B protein can
      specifically activate the expression of the endogenous Dfd transcription unit in
      Drosophila embryos and larvae. We therefore asked whether HOX4B cis-regulatory
      elements could mimic the function of a Dfd autoregulatory element in Drosophila
      embryos. Here we show that a HOX4B upstream element can surprisingly provide
      expression in a posterior head segment of Drosophila. One possible mechanism for
      the axial position-specificity of the human element may involve the conservation
      of a Dfd-specific autoregulatory circuit in both arthropod and chordate lineages.
      This possibility is supported by the finding that a Drosophila Dfd autoregulatory
      element supplies spatially localized expression in the hindbrain of mouse
      embryos.

PMID- 1353610
TI  - Faster superoxide dismutase mutants designed by enhancing electrostatic guidance.
AB  - The enzyme Cu, Zn superoxide dismutase (SOD) protects against oxidative damage by
      dismuting the superoxide radical O2-. to molecular oxygen and hydrogen peroxide
      at the active-site Cu ion in a reaction that is rate-limited by diffusion and
      enhanced by electrostatic guidance. SOD has evolved to be one of the fastest
      enzymes known (V(max) approximately 2 x 10(9) M-1 s-1). The new crystal
      structures of human SOD show that amino-acid site chains that are implicated in
      electrostatic guidance (Glu 132, Glu 133 and Lys 136) form a hydrogen-bonding
      network. Here we show that site-specific mutants that increase local positive
      charge while maintaining this orienting network (Glu----Gln) have faster reaction
      rates and increased ionic-strength dependence, matching brownian dynamics
      simulations incorporating electrostatic terms. Increased positive charge alone is
      insufficient: one charge reversal (Glu----Lys) mutant is slower than the
      equivalent charge neutralization (Glu----Gln) mutant, showing that the newly
      introduced positive charge disrupts the orienting network. Thus,
      electrostatically facilitated diffusion rates can be increased by design,
      provided the detailed structural integrity of the active-site electrostatic
      network is maintained.

PMID- 1353611
TI  - Neurobiology. Modules for molecules.

PMID- 1353612
TI  - [The treatment of disturbed behavior in patients with dementia].

PMID- 1353613
TI  - Kappa opioid agonists inhibit transmitter release from guinea pig hippocampal
      mossy fiber synaptosomes.
AB  - Opioid agonists specific for the mu, delta, and kappa opioid receptor subtypes
      were tested for their ability to modulate potassium-evoked release of L-glutamate
      and dynorphin B-like immunoreactivity from guinea pig hippocampal mossy fiber
      synaptosomes. The kappa opioid agonists U-62,066E and (-) ethylketocyclazocine,
      but not the mu agonist [D-Ala2,N-MePhe4,Gly5-ol]-enkephalin (DAGO) nor the delta
      agonist [D-Pen2,5]enkephalin (DPDE), inhibited the potassium-evoked release of L
      glutamate and dynorphin B-like immunoreactivity. U-62,066E, but not DAGO or DPDE,
      also inhibited the potassium-evoked rise in mossy fiber synaptosomal cytosolic
      Ca2+ levels, indicating a possible mechanism for kappa agonist inhibition of
      transmitter release. DAGO and DPDE were found to be without any effect on
      cytosolic Ca2+ levels or transmitter release in this preparation. The U-62,066E
      inhibition of the potassium-evoked rise in synaptosomal cytosolic Ca2+ levels was
      partially attenuated by the opioid antagonist quadazocine and insensitive to the
      delta-opioid specific antagonist ICI 174,864 and the mu opioid-preferring
      antagonists naloxone and naltrexone. Quadazocine also reversed U-62,066E
      inhibition of the potassium-evoked release of L-glutamate, but not dynorphin B
      like immunoreactivity. These results suggest that kappa opioid agonists inhibit
      transmitter release from mossy fiber terminals through both kappa opioid and non
      kappa opioid receptor mediated mechanisms.

PMID- 1353615
TI  - Colocalization of somatostatin receptors and growth hormone-releasing factor
      immunoreactivity in neurons of the rat arcuate nucleus.
AB  - Recent studies from our group have demonstrated an association of [125I]-labeled
      somatostatin (SRIF)-binding sites with a subpopulation of arcuate (ARC) neurons.
      The distribution of these cells was similar to that of growth hormone-releasing
      factor (GRF)-immunoreactive neurons, which led us to propose that at least some
      SRIF receptors may be directly localized to GRF-containing cells. To test this
      hypothesis, we have visualized radiolabeled SRIF-binding sites and GRF
      immunoreactivity (ir) in adjacent sections of the hypothalamus, by combined
      radioautography and immunohistochemistry. Adult male rats were sacrificed by
      decapitation and the brains were rapidly frozen and serially sectioned on a
      cryostat. Fifteen pairs of adjacent 6-microns-thick sections, taken at 100
      microns intervals through the rostrocaudal extent of the ARC nucleus, were
      alternately processed for [125I]-SRIF radioautography and GRF
      immunohistochemistry. GRF-ir and [125I]-SRIF-labeled cells were mapped at each
      level and quantified with the aid of a camera lucida. The maps were subsequently
      superimposed to determine the extent of [125I]-SRIF/GRF-ir colocalization. GRF-ir
      perikarya [13.2 +/- 4.4 (mean +/- SE) cells per section] were mainly localized in
      the ventrolateral portion of the ARC nucleus and predominated within the caudal
      most tier. [125I]-SRIF-labeled cells (35.6 +/- 6.5 cells per section) were more
      numerous, more evenly distributed, and extended further rostrally and caudally
      than GRF-ir cells. Superimposition of the camera lucida maps indicated that,
      overall, 33.5 +/- 10.8% of the GRF-ir cells were labeled with [125I]-SRIF in
      adjacent sections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353614
TI  - Selective effects of cyanide (100 microM) on the excitatory amino acid-induced
      elevation of intracellular calcium levels in neuronal culture.
AB  - The effect of low concentrations of cyanide on the excitatory amino acid-induced
      elevations of intracellular calcium levels ([Ca2+]i) was studied in cerebellar
      granule cells using ratio fluorometry with fura-2. Glutamate, kainate, N-methyl-D
      aspartate (NMDA), quisqualate (50 microM, each) and membrane depolarization by 40
      mM KCl caused elevations of [Ca2+]i which were 10-, 10-, 3-, 2.3-, 10-fold over
      baseline levels, respectively. Cyanide, 100 microM, greatly augmented the
      increases in [Ca2+]i induced by glutamate, kainate and NMDA but not those induced
      by quisqualate or KCl. In the absence of these excitatory amino acids, cyanide
      had no significant effect in concentrations up to 400 microM. Elevations of
      [Ca2+]i induced by quisqualate and KCl were not significantly augmented by higher
      concentrations of cyanide (400 microM). Selective antagonists could block the
      effect of cyanide+the respective agonist; however, the calcium channel blockers,
      lanthanum and diltiazem lowered both NMDA- and kainate-induced elevations of
      [Ca2+]i, yet neither blocked increases in calcium when 100 microM cyanide was
      added. Collectively, these data support an interaction of cyanide with the
      excitatory amino acid receptor.

PMID- 1353616
TI  - Growth hormone-releasing hormone-synthesizing neurons are a subpopulation of
      somatostatin receptor-labelled cells in the rat arcuate nucleus: a combined in
      situ hybridization and receptor light-microscopic radioautographic study.
AB  - Distribution of growth-hormone-releasing hormone (GHRH) cell bodies and
      somatostatin binding sites were compared in the mediobasal hypothalamus of the
      rat. GHRH-synthesizing neurons were visualized by in situ hybridization, using as
      35S-labelled synthetic oligonucleotide (45 mere), and 125I-Tyr0-DTrp8
      somatostatin (125I-SRIH) binding sites by light-microscopic radioautography on
      adjacent 20-microns-thick frozen mirror sections. GHRH mRNA hybridizing cells
      were detected mostly in the ventrolateral portion of the arcuate nucleus (ARC)
      and around the perimeter of the ventromedial nucleus (VMN). Comparison with the
      distribution of pericellular 125I-SRIH binding sites allowed to differentiate
      three types of cells: (1) GHRH perikarya not associated with pericellular 125I
      SRIH binding sites around the perimeter of the VMN, (2) 125I-SRIH-labelled cells,
      not associated with GHRH perikarya in the periventricular zone along the dorsal
      part of the third ventricle, and (3) in the ventrolateral portion of the ARC,
      GHRH mRNA-labelled neurons had the same distribution as 125I-SRIH-labelled cells.
      Furthermore, on adjacent sections, the number of both labelled cells were
      correlated (r = 0.68; p less than 0.001). In this last population, the extent of
      colocalization of 125I-SRIH binding sites on GHRH mRNA-labelled neurons was
      further investigated in adjacent 5-microns-thick sections. The proportions of
      cells GHRH mRNA and 125I-SRIH allowed to differentiate three subdivisions of the
      arcuate: the periventricular (PV), ventrobasal (VB) and lateral portions. In the
      PV-ARC, 27% of GHRH-synthesizing cells were coidentified as 125I-labelled while
      only 6% of 125I-labelled cells contained GHRH mRNA. In the VB-ARC the proportion
      of double-labelled cells was equivalent (31 and 26%, respectively for GHRH mRNA
      and 125I-SRIH).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353617
TI  - Rett syndrome: stimulation of endogenous biogenic amines.
AB  - Transient hypercapnic hyperoxemia was induced in two Rett syndrome children by
      the administration of a gaseous mixture of 80% O2 and 20% CO2. Time course
      studies of neurotransmitters and their metabolites showed an immediate and marked
      increase in central biogenic amine turnover following inhalation of the gas
      mixture. The increased turnover of biogenic amines was associated with improved
      clinical changes. This suggests a coupled relationship and provides further
      support for an etiological role of neurotransmitter dysfunction in Rett syndrome.
      In a complementary study, elevation of pulmonary CO2 by application of a simple
      rebreathing device resulted in improvement of abnormal blood gases and
      elimination of the Cheyne-Stokes-like respiratory pattern of the Rett syndrome.
      Near normalization of the EEG occurred when a normal respiratory pattern was
      imposed by means of a respirator. Taken together, these results lead to the
      preliminary conclusion that cerebral hypoxemia secondary to abnormal respiratory
      function may contribute to diminished production of biogenic amines in Rett
      syndrome.

PMID- 1353618
TI  - Enhancement of extracellular protein concentrations during long-term potentiation
      in the rat hippocampal slice.
AB  - The possibility that the enhancement of extracellular protein concentrations
      during long-term potentiation is related to the maintenance of long-term
      potentiation was examined in area CA1 of rat hippocampal slices. First, we found
      that during the 3 h after induction, long-term potentiation maintenance was
      correlated with a persistent enhancement of extracellular protein concentrations.
      Second, when the protein synthesis inhibitor cycloheximide was applied 10-15 min
      before long-term potentiation induction, the drug blocked both the maintenance of
      long-term potentiation and the elevation of extracellular protein concentrations.
      These results suggest that the elevation of extracellular protein concentrations
      requires new protein synthesis. The results further indicate that the newly
      synthesized proteins may play a role in the maintenance of long-term
      potentiation.

PMID- 1353619
TI  - Actions of acetylcholinesterase in the guinea-pig cerebellar cortex in vitro.
AB  - Acetylcholinesterase is released in a calcium-dependent manner when afferents of
      the cerebellar cortex are stimulated. Since cholinergic transmission is probably
      insignificant in the cerebellar cortex, the esterase itself might serve as a
      transmitter or modulator. Therefore, the effect of acetylcholinesterase in the
      cerebellum was investigated in slices of guinea-pig cerebella during
      intracellular recording from Purkinje cell somata or dendrites. Addition of
      acetylcholinesterase (20 U/ml) to the superfusion medium did not change the
      membrane potential or the input resistance of the Purkinje cells. Thus, esterase
      does not act like a classical transmitter. The threshold for Na+ spikes generated
      by intracellular current injection was unaffected, but the threshold for Ca2+
      spikes was increased. This increase was abolished by tetrodotoxin (1 microM).
      Furthermore, when Ca2+ currents were blocked by substituting Mn2+ for Ca2+ (2 mM)
      a decrease in a Na+ plateau potential was seen in the presence of esterase. The
      effect of acetylcholinesterase of Ca2+ spikes is therefore most likely due to a
      reduction of the non-inactivating Na+ current of the Purkinje cell membrane. When
      present this current contributes to activation of Ca2+ spikes in dendrites.
      Acetylcholinesterase also enhanced the response of Purkinje cells to the
      excitatory amino acids glutamate and aspartate thought to be transmitters in the
      cerebellar cortex. The responses became larger and faster in the presence of
      esterase. Responses to climbing fibre stimulation were also enhanced by
      acetylcholinesterase. The late part of this synaptic response was increased. The
      potentiation by esterase of responses of Purkinje cells to excitatory amino acids
      and to climbing fibre stimulation may be mediated through interference with
      transmitter uptake, because it was prevented by treatment with DL-2-amino-4
      phosphonobutyric acid (0.5 mM) and di-hydrokainate (0.1 mM). None of the effects
      of esterase was due to hydrolysis of acetylcholine because irreversible
      inhibition of the catalytic site of the enzyme with soman did not prevent the
      actions. The observations were specific for acetylcholinesterase.
      Butyrylcholinesterase (20-40 U/ml) showed none of the effects. It is concluded
      that acetylcholinesterase in the cerebellar cortex seems to mediate a novel type
      of modulation by two separate mechanisms. Esterase reduces the tendency towards
      Ca2+ spike generation in Purkinje cells. Ca2+ spikes are followed by
      afterhyperpolarizations and in their absence firing of Na+ spikes at higher
      frequencies is possible. Secondly, there is an enhancement of the action of
      excitatory transmitters so that the extended operating range can be utilized.

PMID- 1353620
TI  - Extracellular dopamine in striatum: influence of nerve impulse activity in medial
      forebrain bundle and local glutamatergic input.
AB  - Microdialysis probes were used to measure dopamine in, and to administer
      glutamate receptor antagonists and agonists to, the striatum of unanesthetized
      rats. Antagonists used were: kynurenate, 2-amino-5-phosphonovalerate and 6-cyano
      7-nitroquinoxaline-2,3-dione. Agonists used were: N-methyl-D-aspartate and
      kainate. In some rats an additional dialysis probe was implanted in medial
      forebrain bundle for infusion of tetrodotoxin (10 microM) to block action
      potential propagation along dopaminergic axons in this pathway. The latter
      treatment reduced dopamine in striatal dialysate to below detectable levels (less
      than 0.5 pg). The quantity of dopamine in striatal dialysate was not reduced by
      the local application of glutamate receptor antagonists. At lower concentrations,
      the receptor antagonists failed to alter significantly the quantity of dopamine,
      whereas the highest concentration of each antagonist increased the amount of
      dopamine in the dialysate. At the highest concentration tested (0.75 mM or 1.0
      mM), as well as at a lower concentration (0.1 mM), 2-amino-5-phosphonovalerate
      and 6-cyano-7-nitroquinoxaline-2,3-dione blocked the dopamine-releasing effects
      of exogenously applied N-methyl-D-aspartate (1.0 mM) or kainate (0.1 mM),
      respectively. Thus, concentrations of glutamate receptor antagonists that
      produced effective pharmacological blockade of the respective receptors had no
      effect on the basal amount of dopamine in striatal extracellular fluid. Finally,
      N-methyl-D-aspartate and kainate produced a significant elevation in
      extracellular dopamine during the infusion of tetrodotoxin into the medial
      forebrain bundle, indicating that impulse activity in this pathway is not
      necessary for dopamine release produced by glutamate receptor agonists.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1353621
TI  - Aminopeptidases in the circumventricular organs of the mouse brain: a
      histochemical study.
AB  - The localization of four membrane-bound aminopeptidases--aminopeptidase A,
      aminopeptidase M, dipeptidylpeptidase IV, and gamma-glutamyl transpeptidase-
      known as characteristic enzymes of the blood-brain barrier was studied in the
      microvasculature of some circumventricular organs of the mouse brain (subfornical
      organ, area postrema, choroid plexus, and neurohypophysis). Enzyme activities
      were demonstrated histochemically in chloroform-acetone-pretreated cryostat
      sections applying an azo-coupling method. Reactions were evaluated using light
      microscopy and end-point microdensitometry. The results revealed differences in
      microvascular enzyme pattern between circumventricular organs and regions having
      a blood-brain barrier. Moreover, the cytochemical picture of the
      circumventricular organs themselves was not uniform. Dipeptidylpeptidase IV
      reaction showed a strongly reduced activity in the microvessels of all studied
      circumventricular organs. On the other hand, aminopeptidase M seemed to be
      present in both the leaky and the tight capillaries. Only a low activity of
      aminopeptidase A was found in parts of the choroid endothelium and the
      subfornical organ microvasculature. gamma-Glutamyl transpeptidase could neither
      be detected in the capillary part of the choroid plexus nor in the
      neurohypophysis. We are led to conclude that at least dipeptidylpeptidase IV
      might be involved in special mechanisms of the blood-brain barrier.

PMID- 1353622
TI  - Striatal monoamine neurotransmitters and metabolites in dominantly inherited
      olivopontocerebellar atrophy.
AB  - We measured the levels of the monoamine neurotransmitters and metabolites in
      striatum of 14 patients with end-stage dominantly inherited olivopontocerebellar
      atrophy (OPCA). On average, dopamine levels were reduced in putamen (-53%),
      caudate (-35%), and nucleus accumbens (-31%). However, individual patient values
      showed a wide variation, indicating that mild to moderate striatal dopamine loss
      is a common but not constant feature of OPCA. Seven patients had marked putamen
      dopamine loss (-62% to -81%) but without evidence of correspondingly severe
      substantia nigra cell damage; this suggests the possibility of a "dying-back"
      phenomenon in which nerve terminal loss precedes cell body degeneration. Severe
      substantia nigra cell loss with almost total (-95% to -99%) putamen and caudate
      dopamine depletion was present in two patients; however, none of the 14 patients
      had had a clinical diagnosis of parkinsonism or was receiving antiparkinsonian
      medication. Mean striatal serotonin levels were normal, whereas concentrations of
      the serotonin metabolite 5-hydroxyindoleacetic acid were elevated by 47% to 63%;
      this suggests increased activity of raphe dorsalis serotonin neurons innervating
      the striatum, which might aggravate the functional consequences of the dopamine
      deficit.

PMID- 1353623
TI  - N-acetyl-L-aspartate and other amino acid metabolites in Alzheimer's disease
      brain: a preliminary proton nuclear magnetic resonance study.
AB  - We used proton nuclear magnetic resonance spectroscopy in this preliminary study
      of perchloric acid extracts of 12 Alzheimer's disease (AD) and five control brain
      samples to measure the relative levels of taurine, aspartate, glutamine,
      glutamate, gamma-aminobutyric acid (GABA), and the putative neuronal marker, N
      acetyl-L-aspartate (NAA). We found no significant changes in taurine, aspartate,
      or glutamine. NAA was lower in AD compared with control, and this decrease
      correlated with the number of senile plaques and neurofibrillary tangles in
      adjacent tissue sections. GABA levels also were lower in AD brain. Glutamate
      levels were greater in AD than control and showed a close, inverse correlation
      with NAA levels. These findings suggest that the decrease in NAA reflects
      neuronal loss and that remaining neurons could be exposed to a relative excess of
      glutamate and a relative lack of GABA. If present in the neurotransmitter pool,
      this imbalance could result in neurotoxic cell damage. This hypothesis is further
      supported by in vitro and in vivo phosphorus 31 nuclear magnetic resonance
      findings.

PMID- 1353624
TI  - Pretreatment with NMDA antagonists limits release of excitatory amino acids
      following traumatic brain injury.
AB  - After central nervous system (CNS) trauma, there are marked elevations in the
      extracellular levels of excitatory amino acids (EAA), which are believed to
      contribute to delayed tissue damage. Administration of N-methyl-D-aspartate
      (NMDA) receptor antagonists reduces injury severity after brain or spinal cord
      trauma, presumably by blocking the postsynaptic NMDA receptor. In the present
      studies, levels of extracellular amino acids were monitored by microdialysis
      during, and after, a moderately severe fluid-percussion brain injury to rats.
      Pretreatment (15 min prior to injury) with the non-competitive NMDA antagonist
      dextrorphan or the competitive NMDA antagonist CGS 19755 significantly attenuated
      the post-traumatic increase in extracellular glutamate. Pretreatment with
      dextrorphan attenuated the post-traumatic increase in extracellular levels of
      aspartate; although these differences did not reach significance when examined as
      absolute values, they were significant when analyzed as percent increase over pre
      trauma baseline levels. These results are consistent with recent experiments and
      suggest that NMDA antagonists may limit the release of glutamate and aspartate
      after trauma through a presynaptic mechanism.

PMID- 1353625
TI  - [Effect of psychotropic drugs on vigilance and motor performances].
AB  - This review paper deals with the impact of psychotropic drugs on vigilance,
      awakening and motricity. Antidepressants can be divided into 3 categories,
      depending on the subject's awakening: sedatives with a strong anticholinergic
      component, compounds devoid of positive or negative impact on cognition and
      stimulating antidepressants. The principal effect of lithium is to lengthen the
      reaction time. Taken acutely, neuroleptics produce alterations of fine motor
      gestures, but when taken chronically they spare the functioning of cognition.
      Benzodiazepines act on vigilance in various ways, depending on their half-life
      and on their plasma peak time after oral administration. The effect of
      anticonvulsants on cognition is more pronounced with phenytoin and barbiturates
      than with carbamazepine or valproate sodium. The problems of comparative analysis
      in this field and the trends in current studies are underlined.

PMID- 1353626
TI  - [Prevention of gastroduodenal lesions induced by non-steroidal anti-inflammatory
      agents. Economic analysis from a survey of 356 physicians].
AB  - In order to obtain information on prescribing habits concerning the prevention of
      gastroduodenal lesions induced by non-steroidal anti-inflammatory agents (NSAI),
      356 physicians practicing in 2 French departments were asked to fill a posted
      questionnaire. Fifty-one percent of these doctors gave an assessable answer.
      Among these, 84 percent occasionally prescribe "gastric protectors" associated
      with NSAI's in 32 percent of the prescriptions. They use antacids (48 percent),
      anti-H2 products (27 percent), sucralfate (11 percent) or prostaglandins (13
      percent). This represents a daily cost of additional treatment ranging from 0.87
      to 2.49 francs. If fibroscopies and further consultations necessitated by the
      prescription of NSAI's are taken into account, then 86 to 140 percent must be
      added to the cost of NSAI's. The profitability of these preventive measures in
      terms of public health will be really estimated only when the number of severe
      gastroduodenal lesions effectively prevented by taking topical gastric protectors
      or anti-secretory agents will be known.

PMID- 1353627
TI  - The pancreatic duct cell.
AB  - A conference entitled "The Pancreatic Duct Cell: Physiology and Pathophysiology"
      was held September 26-29, 1991, at the Engineering Society Club of Baltimore. The
      conference was organized by a committee consisting of John Williams of the
      University of Michigan (Co-Chair), Daniel Longnecker of Dartmouth Medical School
      (Co-Chair), Barry Agent of Newcastle Upon Tyne, Raymond Frizzell of the
      University of Alabama at Birmingham, Sherwood Githens of the University of New
      Orleans, and Sarah Kalser of the NIDDK. The meeting was sponsored by the NIDDK
      with contributions from NCI, NIDR, ADAMHA, and the American Gastroenterological
      Association. About 100 investigators from the United States, England, Canada,
      Germany, Norway, and Israel attended the conference. The participants were based
      in a number of distinct disciplines including both basic and clinical sciences.
      While the main focus was on pancreatic ducts, comparison of salivary and bile
      ducts was also included.

PMID- 1353628
TI  - The suppression of olfactory bulbectomy-induced muricide by antidepressants and
      antihistamines via histamine H1 receptor blocking.
AB  - The effects of antidepressants [(+)-oxaprotiline, (-)-oxaprotiline, imipramine,
      maprotiline, and trazodone] and antihistamines (mepyramine, dimethindene,
      ketotifen, methapyrilene, and antazoline) on muricidal behaviour in olfactory
      bulbectomized rats were investigated. All drugs except for dimethindene, which
      only minimally passes across the blood-brain barrier, suppressed muricide. The
      drugs which have high affinity for histamine H1 receptor showed potent
      suppressive effect on muricide. It is suggested that the central histaminergic
      system is involved via H1 receptors in the expression of muricide in olfactory
      bulbectomized rats.

PMID- 1353629
TI  - Adrenal hormones in rats before and after stress-experience: effects of
      ipsapirone.
AB  - The present study was designed to investigate the effects of the anxiolytic 5
      HT1A receptor agonist ipsapirone on the hormonal responses in rats under
      nonstress and stress conditions by means of repeated blood sampling through an
      intracardiac catheter. Ipsapirone was given in doses of 2.5, 5, 10, and 20 mg/kg
      (IP) under nonstress conditions in the home cages of the rats. Plasma
      corticosterone levels increased in a dose-dependent way in the dose range of 5 to
      20 mg/kg, whereas the plasma catecholamines were only significantly increased
      with the highest dose of the drug. The effect of ipsapirone in control and in
      stressed rats was studied with the selected dose of 5 mg/kg. Conditioned fear of
      inescapable electric footshock (0.6 mA, AC for 3 s) given one day earlier was
      used as stressor. Surprisingly, ipsapirone potentiated the magnitude of the
      neuroendocrine responses. Rats receiving an inescapable footshock 1 day earlier
      showed a further elevated corticosterone response to the 5-HT1A receptor agonist
      ipsapirone even before exposing them to the conditioned stress situation. The
      present findings suggest that if an animal has no possibilities to escape or
      avoid a noxious event, functional hypersensitivity will develop in the
      serotonergic neuronal system, which is reflected in the increased responsiveness
      of the HPA axis to a 5-HT1A agonist challenge.

PMID- 1353630
TI  - Alpha 2-adrenergic modulation of pancreatic glucagon secretion in rats.
AB  - The present study was designed to clarify the mechanism of adrenergic modulation
      of pancreatic glucagon secretion in rats under physiological conditions by 1)
      epinephrine infusion alone or together with adrenergic blockers and 2)
      administration of adrenergic agonists. Intravenous infusion of epinephrine alone
      (1 microgram/kg/min, equal to 0.7 nmol/kg/min) caused a significant increase in
      glucagon secretion. Phentolamine (an alpha blocker) or yohimbine (an alpha 2
      blocker) administration completely inhibited the increase of glucagon secretion
      caused by epinephrine infusion, but neither the administration of bunazosin (an
      alpha 1 blocker) nor beta blockers inhibited it. Infusion of clonidine (an alpha
      2 agonist) caused significant increase of glucagon secretion even at a low dose
      of 0.5 nmol/kg/min, although infusion of neither an alpha 1 nor a beta 2 agonist
      caused it even at the high dose of 40.0 nmol/kg/min. It is concluded that the
      alpha 2 receptor mechanism plays the most important role in the adrenergic
      modulation of glucagon secretion in rats under physiological conditions.

PMID- 1353631
TI  - Influence of the acute stress on agonist-stimulated phosphoinositide hydrolysis
      in the rat cerebral cortex.
AB  - 1. The present study was carried out in order to elucidate the influence of the
      acute stress on alpha 1-adrenergic, serotonin-2 (5-HT2) and muscarinic
      cholinergic (M-Ach) receptors-mediated phosphoinositide (PI) hydrolysis in rat
      cerebral cortex slices. 2. In rat cerebral cortex slices, noradrenaline (NA),
      serotonin (5-HT) and carbachol stimulated [3H]inositol-monophosphate (IP1)
      accumulation in a concentration-dependent manner. 3. The forced swimming test
      (FST) for 15 min induced a significant reduction of 5-HT-stimulated [3H]IP1
      accumulation, but this stress situation did not produce a significant alteration
      of NA- and carbachol-stimulated [3H]IP1 accumulation. 4. The FST for 15 min did
      not affect the density and affinity of alpha 1-adrenergic, 5-HT2 and M-Ach
      receptors. 5. In a mild acute stress situation, the intracellular signal
      transduction mediated by 5-HT was promptly inhibited as compared to the signal
      transduction mediated by NA or carbachol. This inhibition may be induced by an
      acute uncoupling of 5-HT2 receptor-mediated intracellular signal transduction.

PMID- 1353632
TI  - A model of interaction between Entamoeba histolytica and Shigella flexneri.
AB  - The establishment of a relationship between Entamoeba histolytica and certain
      bacteria may contribute to the expression and/or enhancement of the pathogenicity
      of this parasite. Recent experiments have shown that bacteria expressing mannose
      binding lectins on their surface could attach to mannose-containing molecules on
      the surface of amoebae. In this study, we established a model of interaction
      between. E. histolytica and Shigella flexneri. Using well-characterized mutants
      of S. flexneri, we studied the role of type I pili expression and the invasive
      phenotype of S. flexneri in the interaction between amoebae and the bacteria.
      Type I pili expression allowed attachment and subsequent internalization of S.
      flexneri by amoebae, these events were not observed in isogenic strains that did
      not express type I pili. Invasive as well as non-invasive variants of S. flexneri
      expressing type I pili were slowly digested by amoebae following internalization.
      Morphological studies showed that the specific features of the interaction depend
      on the dynamics of the distribution of mannose residues on the amoebic membrane
      during the interaction.

PMID- 1353633
TI  - CD4+ cells and CD4+ percent as risk markers for Pneumocystis carinii pneumonia
      (PCP): implications for primary PCP prophylaxis.
AB  - The incidence of Pneumocystis carinii pneumonia (PCP) during 2 years in HIV
      infected patients with less than or equal to 100 x 10(6)/l CD4+ cells, less than
      or equal to 200 x 10(6)/l CD4+ cells and less than 20% CD4+ cells of total T
      lymphocytes were compared. The relative PCP risk in 57 patients with less than or
      equal to 100 CD4+ cells was more than twice higher than in 120 patients with less
      than or equal to 200 CD4+ cells. The latter had almost twice higher relative PCP
      risk than 271 patients with less than or equal to 20% CD4+ cells. Only 3/56
      patients who acquired PCP had greater than 200 CD4+ cells and 15/56 patients had
      greater than 100 CD4+ cells. Centers for Disease Control (CDC) recommends primary
      PCP prophylaxis in HIV-infected patients when the number of CD4+ cells is less
      than 200 x 10(6)/l or when the CD4+ is less than 20. On the basis of the
      presented data we suggest that primary prophylaxis is considered only when CD4+
      cells fall below 200 x 10(6)/l.

PMID- 1353634
TI  - Limited clinical usefulness of tests for P-fimbriated Escherichia coli in
      patients with urinary tract infections.

PMID- 1353635
TI  - From macro to microdoses -- reference values for toxic metals. Proceedings of a
      workshop. Brescia, Italy, April 5, 1990.

PMID- 1353636
TI  - A comparison of dilution adjustment methods for urinary enzymes.
AB  - Urinary dilution adjustment methods can be used to reduce the intra-individual
      variability in concentrations of metals and other substances in urine due to
      variability in urinary flow. In this study linear and non-linear dilution
      adjustments with urinary flow, creatinine (CREAT) and urinary density (UD) were
      compared for the urinary enzymes alanine amino peptidase (AAP), beta
      galactosidase (beta GAL) and N-acetyl-beta, D-glucosaminidase (NAG). The most
      optimal dilution adjustment for AAP was: AAPadjusted =
      AAPmeasured/(CREATmeasured)0.824 The optimal dilution adjustment for beta GAL
      was: beta GALadjusted = beta GALmeasured/(CREATmeasured)0.878 For NAG the optimal
      dilution adjustment parameter was the conventional linear adjustment with SG. It
      could not be determined whether urinary dilution methods can be useful for
      population based reference intervals of urinary enzymes. If personal reference
      intervals can be calculated, urinary dilution adjustment methods may be useful by
      reduction of intraindividual variability.

PMID- 1353637
TI  - A Mac-1 antibody reduces liver and lung injury but not neutrophil sequestration
      after intestinal ischemia-reperfusion.
AB  - BACKGROUND: Intestinal ischemia and reperfusion (I/R) result in
      leukosequestration and injury to the liver and lungs. The adherence-dependent
      oxidative burst of neutrophils requires cell adhesion through the Mac-1 integrin.
      Neutrophil-mediated tissue injury may depend on this specific cell adhesion
      event. This study tests the effect of a Mac-1 (CD 11b) monoclonal antibody (MAb)
      (R17) on liver and lung injury after intestinal I/R. METHODS: After collaterals
      were ligated in anesthetized rats, the superior mesenteric artery was clamped for
      60 minutes followed by 3 hours of reperfusion. Animals were treated with saline
      solution, R17, or nonspecific immunoglobulin M. Another nonischemic group of rats
      were sham controls. Lung and intestinal polymorphonuclear leukocyte sequestration
      was assessed by measurement of myeloperoxidase and lung permeability by
      bronchoalveolar lavage blood concentration ratio of 125I-labeled bovine serum
      albumin. RESULTS: At 3 hours of reperfusion lung and intestinal myeloperoxidase
      and lung permeability were increased. Treatment with R17 MAb did not reduce
      intestinal or lung myeloperoxidase but prevented increased lung permeability.
      Similarly, after treatment with saline solution, liver polymorphonuclear
      leukocyte sequestration increased after 3 hours of reperfusion, and serum alanine
      aminotransferase level rose eightfold. R17 MAb did not significantly reduce liver
      neutrophil sequestration; however, it reduced alanine aminotransferase level more
      than 50% when compared to saline solution controls. At 3 hours of reperfusion
      there was a leukocytosis (white blood cell count, 14.9 +/- 1.0 x 10(3)/mm3 vs 6.0
      +/- 0.8 in sham [p less than 0.05]). The white blood cell count was unaffected by
      R17 MAb. CONCLUSIONS: These data indicate that a MAb to the neutrophil Mac-1
      integrin reduces lung and liver injury after intestinal I/R but does not reduce
      lung or intestinal leukosequestration.

PMID- 1353638
TI  - Amplification of the HER-2/neu protooncogene in human endocrine tumors.
AB  - BACKGROUND: Amplification of HER-2/neu, a protooncogene related to the epidermal
      growth factor receptor, has prognostic significance in patients with breast
      cancer. Alterations in protooncogenes have not been determined for endocrine
      tumors in which prognosis is difficult to predict. We have addressed the question
      of whether amplification of HER-2/neu or epidermal growth factor receptor occurs
      in DNA from human endocrine tumor lines and have sought to characterize the HER
      2/neu gene and its products in carcinoid tumors of the gut. METHODS: The
      differential polymerase chain reaction procedure was used to detect genomic
      amplification in DNA samples from human endocrine tumor cell lines (BON, SIM,
      STAN) and from paraffin-embedded samples of carcinoid tumors. Sequencing
      techniques were used to determine whether mutations of the transmembrane domain
      of HER-2/neu existed. We then further characterized the gene products (RNA and
      protein) in carcinoid tumors. RESULTS: Amplification of HER-2/neu was identified
      in all three endocrine tumor cell lines. HER-2/neu amplification was found in
      four of 10 carcinoid tumors of the gut; three of these four tumors were invasive
      or metastatic. In addition, HER-2/neu mRNA and protein were expressed in
      carcinoid tumors. CONCLUSIONS: Amplification of the HER-2/neu protooncogene
      occurs in endocrine tumors of the gut; quantitation of the actual copy number may
      be an important prognostic determinant. The unique human endocrine cell lines,
      established in our laboratory, will be useful models to further examine the
      significance of alterations of the HER-2/neu gene in endocrine tumors.

PMID- 1353639
TI  - Presymptomatic identification of carriers of the multiple endocrine neoplasia
      type 2A gene using flanking DNA markers.
AB  - BACKGROUND: Because the predisposition locus for multiple endocrine neoplasia
      type 2A (MEN2A) has been mapped to chromosome 10 by genetic linkage analysis, it
      has become possible to identify gene carriers by following the transmission of
      linked genetic markers from affected parents to offspring at risk for MEN2A. We
      have applied a highly accurate genetic test to presymptomatic diagnosis of gene
      carriers in several large kindreds with MEN2A. METHODS: DNA was extracted from
      300 individuals in six kindreds with MEN2A and used for genotyping studies with
      DNA markers flanking the MEN2A locus. Genotype data were used to predict the
      inheritance of the MEN2A gene in kindred members at risk according to previously
      calculated map distances and the program LINKAGE: RESULTS: Ninety-five percent of
      individuals were informative with markers flanking the MEN2A locus. Of 130
      patients at risk, 26 (20%) were predicted to be MEN2A gene carriers, 100% (77%)
      were noncarriers, and 4 (3%) were recombinant and their gene carrier status could
      not be determined. Gene carrier prediction probabilities were calculated at
      greater than 98% in 94% of these patients. CONCLUSIONS: We conclude that genetic
      testing with flanking DNA markers is a highly accurate method for the
      presymptomatic identification of MEN2A gene carriers and allows for diagnosis at
      an earlier stage than does traditional calcitonin testing.

PMID- 1353640
TI  - Decreased leukocyte adhesion with anti-CD18 monoclonal antibodies is mediated by
      receptor internalization.
AB  - BACKGROUND: Adhesion of polymorphonuclear leukocytes (PMNs) to endothelial cells
      is mediated partially by CD11/CD18 integrins. The purpose of this study was to
      define (1) the response of PMNs to anti-CD18 monoclonal antibody binding, and (2)
      the mechanism responsible for anti-CD18 monoclonal antibody-mediated decreases in
      PMN adhesion to endothelial cells. METHODS: Canine PMN O2- production,
      myeloperoxidase, and lysozyme release in response to the anti-CD18 monoclonal
      antibody IB4 were measured by standard assays. To examine endocytosis of CD18
      receptors, PMNs incubated with IB4 and a fluorescein isothiocyanate secondary
      antibody were analyzed by flow cytometry. RESULTS: Treatment of PMNs with IB4 did
      not stimulate O2- production or degranulation but decreased adhesion of 51Cr
      labeled PMNs to ex vivo canine aorta. Incubation of PMNs at 25 degrees C resulted
      in a decrease in fluorescence intensity that was not affected by NaN3 or vanadate
      but was blocked by NaF, 4 degrees C, and bafilomycin, which prevents endosomal
      acidification. Treatment with an antifluorescein antibody decreased the
      fluorescence intensity in NaF and 4 degrees C, but not in bafilomycin-treated
      neutrophils. CONCLUSIONS: IB4 decreases PMN-endothelial cell adhesion but does
      not stimulate neutrophil oxidative metabolism or degranulation. These data
      suggest that reduced adhesion may be the result of internalization of the
      CD18/IB4 complex. Anti-CD18 monoclonal antibodies may be useful in preventing PMN
      adhesion without the potentially deleterious effects of cell activation.

PMID- 1353641
TI  - Independent modulation of enterocyte migration and proliferation by growth
      factors, matrix proteins, and pharmacologic agents in an in vitro model of
      mucosal healing.
AB  - BACKGROUND: Gastrointestinal mucosa heals by restitution and proliferation. These
      are difficult to distinguish in vivo. METHODS: Human Caco-2 enterocytes were
      cultured on matrix proteins (collagen I, laminin, fibronectin) with growth
      factors (epidermal growth factor [EGF] and transforming growth factor-beta 1 [TGF
      beta 1]) and the tyrosine kinase and prostaglandin inhibitors genistein and
      indomethacin. Healing was modeled by means of monolayer expansion, proliferation
      by means of 3H-thymidine uptake, and restitution by means of mitomycin-blocked
      migration. RESULTS: Changing matrix composition failed to alter proliferation,
      but collagen I stimulated migration more than laminin or fibronectin
      (laminin/collagen, 68% +/- 2%; p less than 0.05). EGF (30 ng/ml) increased
      proliferation on both collagen (225% +/- 11% of basal) and laminin (206% +/- 26%)
      but increased migration only over laminin (210% +/- 17%) (all, p less than 0.05).
      TGF-beta 1 (200 pg/ml) stimulated migration over laminin (187% +/- 18%, p less
      than 0.005) but inhibited migration over collagen (89% +/- 3%, p less than 0.01)
      and did not affect 3H-thymidine uptake. When cultured on laminin, EGF but not TGF
      beta 1 altered organization of the alpha 2 integrin subunit. Genistein (100
      mumol/L) inhibited basal and EGF-stimulated 3H-thymidine uptake. In addition, it
      prevented EGF stimulation of replication-blocked migration (81% +/- 10% vs 190%
      +/- 20% of basal, p less than 0.0001) without altering basal replication-blocked
      migration. Indomethacin (10(-5) mol/L) did not alter migration but inhibited
      basal and EGF-stimulated proliferation by 7% +/- 1% (each, p less than 0.005).
      CONCLUSIONS: Restitution and proliferation appear independently regulated by
      matrix and growth factors. It may be possible to individually target specific
      phases of mucosal healing by means of pharmacologic agents.

PMID- 1353642
TI  - Immune status of asymptomatic HIV-infected hemophiliacs: randomized, prospective,
      two-year comparison of treatment with a high-purity or an intermediate-purity
      factor VIII concentrate.
AB  - It has been postulated that high-purity factor VIII (FVIII) concentrates, since
      they contain less alloantigenic proteins than intermediate-purity concentrates,
      might cause lesser deterioration of the immune systems of hemophilic patients
      infected with the human immunodeficiency virus (HIV). To evaluate this
      hypothesis, we have prospectively compared T-lymphocytes subsets and delayed
      hypersensitivity reactions to skin tests in 17 asymptomatic HIV-positive
      hemophiliacs randomly assigned to continue treatment with an intermediate-purity
      concentrate with those of 16 hemophiliacs changed to a high-purity concentrate.
      For both groups, during the 24-month follow-up period CD4 cell counts showed
      similar rates of fall from baseline values. There was also no difference in the
      number of patients anergic to skin tests. Three patients treated with the
      intermediate purity concentrate and one treated with the high-purity concentrate
      developed symptoms of HIV infection. On the whole, no striking benefit is
      conferred to the immune status of asymptomatic HIV-positive hemophiliacs by using
      this high-purity concentrate for 2 years.

PMID- 1353643
TI  - Activation of bovine plasma benzylamine oxidase (BzAO) by 1-methyl-4-(2
      methylphenyl)-1,2,3,6-tetrahydropyridine.
AB  - We have shown previously that certain analogues of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) are potent inhibitors of human and bovine plasma
      benzylamine oxidase (BzAO: EC 1.4.3.6). Inhibition was competitive, reversible
      and allosteric. Under certain conditions competitive inhibitors of allosteric
      enzymes can act as allosteric activators. In the present work, 1-methyl-4-(2
      methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH3MPTP) was found to activate
      bovine plasma BzAO at low substrate and 2'-CH3MPTP concentrations. At higher 2'
      CH3MPTP concentrations, the activation was negated.

PMID- 1353644
TI  - [The role of intermediate filaments in forming cellular processes induced in
      fibroblasts by the tumor promoter TPA].
AB  - A tumor promoter phorbol 12-myristate 13-acetate (PMA) induces characteristic
      reversible changes in the cell shape in certain fibroblastic lines. This reaction
      to PMA may be regarded as a prototype of reorganizations involving formation of
      stable cytoplasmic processes. Two specific drugs, Taxol and Colcemid, were used
      to study the role of microtubules and vimentin-containing intermediate filaments
      (IF) in the development of PMA-induced reorganizations. A short (I h) exposure to
      PMA induced formation of processes in the control cells rather than in the
      Colcemid treated cells having depolymerized microtubules and the IF that
      collapsed around the nucleus. A longer (3-4 h) exposure to PMA of the colcemid
      treated cells induced a partial reversal of the IF collapse; those parts of
      peripheral lamellae that contained IF were transformed into narrow noncontractile
      processes. It is suggested that the local interaction of the IF with the actin
      system is an essential step in the formation of processes from lamellae.

PMID- 1353645
TI  - Distribution of polymorphic HLA-DR and -DQ alleles as determined by restriction
      fragment length polymorphism analysis in an Austrian population.
AB  - The restriction fragment length polymorphism (RFLP) of HLA-DR beta, -DQ alpha and
      -DQ beta genes was analyzed in 637 unrelated individuals from the Austrian
      population. The restriction enzyme was Taq I, and three exon-specific probes were
      applied. The gene frequencies, the Hardy-Weinberg equilibrium in DR beta and DQ
      loci, linkage disequilibria between the loci and haplotype frequencies are
      calculated. Rare associations between DR and DQ loci are described. Two RFLP
      patterns are demonstrated which were unique in the overall 1,000 individuals
      tested so far.

PMID- 1353646
TI  - Combination of GM-CSF and cytosine in myelodysplasia results in improved
      neutrophil function.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) was given concurrently
      with low-dose cytosine arabinoside for 3 weeks to patients with myelodysplasia.
      Neutrophil activation as evidenced by increased chemiluminescence and reduced
      surface expression of CD16 was consistently seen during therapy. An attendant
      fall in chemotaxis was also observed. These effects occurred even when neutrophil
      counts did not rise significantly at lower doses of GM-CSF. Although no
      improvement in anaemia or thrombocytopenia was observed, the neutrophil counts
      became normal during therapy without significant expansion of marrow cellularity
      or colony-forming ability. No major toxicities were observed, even at higher
      dosages of GM-CSF.

PMID- 1353648
TI  - Ultrastructural localization of dipeptidylpeptidase IV in the glomerulum of the
      rat kidney.

PMID- 1353647
TI  - Immunohistochemical localization of calcitonin gene-related peptide and
      cotransmitters in a subpopulation of post-ganglionic neurons in the porcine
      inferior mesenteric ganglion.
AB  - Applying double-fluorescence immunohistochemistry, adrenergic and non-adrenergic
      postganglionic sympathetic neurons, in the porcine inferior mesenteric ganglion
      (IMG) are subdivided according to size and cotransmitter content. Calcitonin gene
      related peptide (CGRP)-immunoreactive (IR) neurons are demonstrated to belong to
      the non-adrenergic, i.e. tyrosine hydroxylase- and DOPAmine-beta-hydroxylase-(D
      beta H)-negative subpopulation of postganglionic perikarya. Virtually all of the
      CGRP-IR postganglionic neurons exhibit colocalization with somatostatin (SOM),
      and, some of them with neuropeptide tyrosine (NPY). Additionally, NPY-, SOM-, and
      NPY/SOM-IR subpopulations of adrenergic and non-adrenergic neurons are observed.
      CGRP-immunoreactivity is seen in dense networks of intraganglionic varicose nerve
      fibres, adjacent to the TH- and SOM-IR neurons. NPY-IR perikarya are sparsely
      supplied by CGRP-IR fibres. SOM- and NPY-IR nerve fibres also exist in the
      inferior mesenteric ganglion. The functional relevance of CGRP-IR postganglionic
      neurons, as well as target organs of these neurons remain to be elucidated.

PMID- 1353649
TI  - Glutamate and GABA levels in CSF from patients affected by dementia and olivo
      ponto-cerebellar atrophy.
AB  - The modifications in the CSF content of glutamate and GABA in patients afflicted
      with primary degenerative dementia (PDD) and olivo-ponto-cerebellar atrophy
      (OPCA) have been evaluated. Control subjects (with disk herniation) were also
      included in the study. The amino-acids assays were carried out utilizing
      enzymatic-bioluminescence technique. GABA levels in controls were 803 +/- 98 (n =
      7) and in demented patients 702 +/- 98 (n = 7) pmol/ml. Glutamate levels were
      2067 +/- 244 (n = 10) in controls, 1190 +/- 81 (n = 16) pmol/ml (vs controls p
      less than 0.01) in demented patients, and 1116 +/- 146 (vs controls p less than
      0.01) in OPCA patients. These results suggest that CSF glutamate levels in
      severely demented patients might be a result of generalized neuronal loss in the
      brain with a reactive gliosis.

PMID- 1353651
TI  - Auricular acupuncture for smoking.

PMID- 1353650
TI  - Common factors contributing to intractable pain and medical problems with
      insufficient drug uptake in areas to be treated, and their pathogenesis and
      treatment: Part I. Combined use of medication with acupuncture, (+) Qi gong
      energy-stored material, soft laser or electrical stimulation.
AB  - Most frequently encountered causes of intractable pain and intractable medical
      problems, including headache, post-herpetic neuralgia, tinnitus with hearing
      difficulty, brachial essential hypertension, cephalic hypertension and
      hypotension, arrhythmia, stroke, osteo-arthritis, Minamata disease, Alzheimer's
      disease and neuromuscular problems, such as Amyotrophic Lateral Sclerosis, and
      cancer are often found to be due to co-existence of 1) viral or bacterial
      infection, 2) localized microcirculatory disturbances, 3) localized deposits of
      heavy metals, such as lead or mercury, in affected areas of the body, 4) with or
      without additional harmful environmental electro-magnetic or electric fields from
      household electrical devices in close vicinity, which create microcirculatory
      disturbances and reduced acetylcholine. The main reason why medications known to
      be effective prove ineffective with intractable medical problems, the authors
      found, is that even effective medications often cannot reach these affected areas
      in sufficient therapeutic doses, even though the medications can reach the normal
      parts of the body and result in side effects when doses are excessive. These
      conditions are often difficult to treat or may be considered incurable in both
      Western and Oriental medicine. As solutions to these problems, the authors found
      some of the following methods can improve circulation and selectively enhance
      drug uptake: 1) Acupuncture, 2) Low pulse repetition rate electrical stimulation
      (1-2 pulses/second), 3) (+) Qi Gong energy, 4) Soft lasers using Ga-As diode
      laser or He-Ne gas laser, 5) Certain electro-magnetic fields or rapidly changing
      or moving electric or magnetic fields, 6) Heat or moxibustion, 7) Individually
      selected Calcium Channel Blockers, 8) Individually selected Oriental herb
      medicines known to reduce or eliminate circulatory disturbances. Each method has
      advantages and limitations and therefore the individually optimal method has to
      be selected. Applications of (+) Qi Gong energy stored paper or cloth every 4
      hours, along with effective medications, were often found to be effective, as
      Qigongnized materials can often be used repeatedly, as long as they are not
      exposed to rapidly changing electric, magnetic or electro-magnetic fields.
      Application of (+) Qi Gong energy-stored paper or cloth, soft laser or changing
      electric field for 30-60 seconds on the area above the medulla oblongata,
      vertebral arteries or endocrine representation area at the tail of pancreas
      reduced or eliminated microcirculatory disturbances and enhanced drug
      uptake.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1353652
TI  - Clinical research on treating senile dementia by combining acupuncture with
      acupoint-injection.
AB  - Combining acupuncture with acupoint-injection of aceglutamidi has been used in
      treating 38 cases of senile dementia. Our experiment showed that the therapy is
      effective for the cases of multi-infarct dementia, the rate of success being
      42.85% and of improvement 42.86%, the total efficacy rate being 85.71%. The
      rating was based on the revised Hasegawa Dementia Scale and the Functional
      Activity Questionnaire. In addition, it has been observed that the component of
      high density lipid-cholesterone increased significantly after treatment.

PMID- 1353653
TI  - Detection of extraordinary large bio-magnetic field strength from human hand
      during external Qi emission.
AB  - It is generally accepted that more than 10(-6) gauss order magnetism was not
      detected in normal human condition. However, we detected 10(-3) gauss (mGauss)
      order bio-magnetic field strength from the palm in special persons who emitted
      External Qi ("Chi" or "Ki"). This detection was possible by special arranged
      magnetic field detection system, consisted of a pair of 2 identical coils with
      80,000 turns and a high sensitivity amplifier. Each of the coils were rolled
      80,000 turns accurately, and were connected in series in opposite direction,
      actuating as a gradiometer. We measure bio-magnetic field strength in 37 subjects
      with this detection system. The only 3 subjects of them exhibited strong bio
      magnetic field of 2 to 4 mGauss in frequency range of 4 to 10 Hz. This magnetic
      field strength was greater than that of normal human bio-magnetism by 1,000 times
      at least. A simultaneous measurement of bio-magnetic field strength and its
      corresponding bio-electric current was examined in one subject. During exhibiting
      such strong bio-magnetism, its corresponding electric current was not detectable.
      Therefore, the extra-ordinary large bio-magnetic field strength can not derive
      from internal body current alone, hence the origin of the large bio-magnetism is
      still unknown. We suppose that the extraordinary large bio-magnetic field
      strength might be originated from "Qi" energy in the oriental medicine or in the
      oriental traditional philosophy.

PMID- 1353654
TI  - Acupuncture-like stimulation with codetron for rehabilitation of patients with
      chronic pain syndrome and osteoarthritis.
AB  - Acupuncture is one of the oldest healing methods which is used in traditional
      medicine. In the modern medicine, we are witnessing a renaissance of this ancient
      treatment applied mainly in the management of chronic pain. A number of modern
      technological changes are being applied to replace, or modify, the classical
      needle treatment. Among many modalities used today is the novel addition in
      Transcutaneous Electrical Nerve Stimulation (TENS) called CODETRON which delivers
      acupuncture-like stimulation in a random order. CODETRON was developed by a
      Canadian Scientist and had been evaluated in a clinical trial in a
      multidisciplinary pain clinic on patients who came for acupuncture therapy over a
      period of two years. Indications, effectiveness and experiences with this form of
      treatment are presented. In addition, results obtained from a six week double
      blind randomized placebo controlled pilot trial of osteoarthritis of the hip/knee
      with CODETRON which was conducted later. The results were highly suggestive of
      the beneficial effect of this nonhabituating mode of therapy and confirmed our
      initial uncontrolled trial results.

PMID- 1353655
TI  - Treating poisonings: focus on syrup of ipecac.
AB  - The awareness of poison prevention is increasing despite an alarming incidence of
      accidental and intentional poisonings in the United States. During 1990, 72
      poison centers throughout the United States, serving a population of 191.7
      million, submitted to the American Association of Poison Control Centers data
      collection system 1,713,462 cases of poisonings, which included 612 deaths.
      Emetic agents, when used properly, can reduce the extent and severity of
      improperly ingested medications, selected household products, and other toxic
      chemicals. The pharmacist can play a valuable role in distributing information
      about poison control centers, poison prevention, and appropriate treatment of
      poisonings.

PMID- 1353656
TI  - Commentary: management of acute poisoning.

PMID- 1353657
TI  - Assessment of ventricular performance after chronic beta-adrenergic blockade in
      the Marfan syndrome.

PMID- 1353658
TI  - Sulfasalazine desensitization in children and adolescents with chronic
      inflammatory bowel disease.
AB  - Sulfasalazine is an important therapeutic agent in the management of chronic
      inflammatory bowel disease (CIBD). Unfortunately, adverse reactions to this drug
      have been reported in 5-55% of treated patients. These include dose-related side
      effects like nausea, malaise, and headache or hypersensitivity reactions such as
      rash, fever, hives, arthralgia, hepatitis, etc. Studies in adults with successful
      reintroduction of sulfasalazine after a desensitization program have been
      reported; however, with regard to children, no such data are available. Fourteen
      children and adolescents (5-16 yr old) diagnosed to have CIBD manifested
      hypersensitivity to sulfasalazine within 2 months of onset of treatment. All had
      pancolitis--secondary to Crohn's disease (CD) in four and to ulcerative colitis
      (UC) in 10. All of them were on steroids. Sulfasalazine was discontinued in all
      after symptoms of hypersensitivity developed. Three patients with severe reaction
      were diagnosed prior to desensitization experience. Desensitization, beginning
      with 5-50 mg of sulfasalazine/day, was attempted in the other 11 children. The
      dose was gradually increased by 5-50 mg increments every 3 days. Desensitization
      was successful in only five children, who were ultimately able to tolerate 1.5
      3.0 g of sulfasalazine daily again. In the rest (six of 11 patients), oral 5-ASA
      (Asacol) was administered, and three could not tolerate it. One of these three
      with intolerance to Asacol required colectomy. One did not tolerate Asacol or
      Dipentum. Our findings suggest that sulfasalazine desensitization should be
      attempted in all patients developing hypersensitivity reactions before trying
      alternative therapy.

PMID- 1353659
TI  - Physicians' assistants doing endoscopy?

PMID- 1353660
TI  - Physician assistants in gastroenterology: should they perform endoscopy?
AB  - New technology and increased screening examinations continue to cause the demand
      for gastrointestinal endoscopic procedures to mushroom. Hospitals administered by
      the Department of Veterans Affairs, public health care facilities, and health
      maintenance organizations struggle to meet this demand because of limited
      resources for expansion of space or staff. For the past 3 yr, we have used a
      physician assistant in our endoscopy laboratory to assist with and perform
      endoscopic procedures. The benefits for our hospital include increased staff
      efficiency, improved housestaff education, and ability to perform an increased
      number of procedures with existing staff.

PMID- 1353661
TI  - Optimizing the information obtained from continuous 24-hour gastric pH
      monitoring.
AB  - Our objective in performing this study was to determine the best way to summarize
      experimental data obtained from 24-h continuous intragastric pH-metry. For this
      purpose, we reviewed 605 circadian intragastric pH recordings performed under
      different clinical conditions. Included were 82 normal subjects, 126 patients
      with active duodenal ulcer, 272 ulcer patients in clinical remission treated with
      a single bedtime dose (at 10 PM) of various H2 antagonists and 125 patients with
      active ulcer treated with a single morning dose (8 AM) of omeprazole. For each
      group, we calculated the time spent at different pH levels scaled with 0.1
      incremental steps in three different time intervals: 24 h (5 PM to 4:59 PM),
      daytime (8 AM to 7:59 PM), and nighttime (8 PM to 7:59 AM). Then we calculated
      the mean and the median pH, as well as the time spent in min greater than 3.0 pH
      units over a mainly drug-related time window (8 PM to 7:59 AM) for each treatment
      and its respective placebo group. The mean and the median pH, as well as the time
      spent in minutes greater than 1.2 pH units over 24 h were also calculated for the
      untreated groups of normal subjects and duodenal ulcer patients. Considering the
      individual pH recordings, bi- or plurimodal density distributions of pHs were
      found in more than 90% of the 605 subjects, no matter the time window and the
      clinical condition examined, and log-normal distributions were found in only
      three cases. Considering the groups instead of single pH recordings, conversely,
      normal subjects and duodenal ulcer patients showed average left-skewed unimodal
      density distributions, whereas bimodal patterns were the rule in the groups of
      patients treated with H2 antagonists and omeprazole. The time spent greater than
      3.0 pH units was the most powerful acidity index in assessing drug effectiveness
      in the various subsets of antisecretory compounds, in that the Student's t test
      values obtained with this variable were almost invariably higher than those
      obtained with the mean and median pH levels. Also, the time spent greater than
      1.2 pH units was the most powerful summary variable in differentiating normal
      subjects from duodenal ulcer patients (p less than 0.01, compared with the mean
      and median pH). We conclude that the time spent above a given pH threshold of
      interest is a more accurate index than the mean and median pH in summarizing
      gastric acidity changes under all clinical conditions, and this is because it
      better represents the experimental pH measurements from which it comes.

PMID- 1353662
TI  - Diagnostic value of serum gamma-glutamyl transferase isoenzyme for hepatocellular
      carcinoma: a 10-year study.
AB  - Serum gamma-glutamyl transferase (GGT) was separated into nine to 11 isoenzyme
      bands (designated as GGT I-XI) by vertical slab electrophoresis on polyacrylamide
      gradient gel. The diagnostic value of GGT isoenzyme II (GGT II) for
      hepatocellular carcinoma (HCC) was studied, and the results were as follows: 1)
      GGT II was positive in 90% of 90 cases of HCC, and negative in most patients with
      acute and chronic viral hepatitis, extrahepatic tumors, in pregnant women, and in
      healthy controls; 2) the positive rate of GGT II assay was higher than that of
      alkaline phosphatase isoenzyme I (ALP I), alpha-fetoprotein (AFP), and alpha 1
      antitrypsin (AAT) in 101 cases of HCC. In cases in which the AFP was greater than
      50 ng/ml or less than 50 ng/ml, the positive rates of GGT II were 70.8% and 75
      100%, respectively; 3) of 14 cases of small-size HCC, the positive rate of GGT II
      was 78.6%, which was higher than that of AFP (50%), AAT (28.6%), and ALP I (0%);
      4) of 62 cases that were false-positive for GGT II assay, 24.2% developed into
      HCC during a follow-up of 2.1-20 months. In subjects with persistent and
      recurrent positivity of GGT II, 86.7% and 22.2%, respectively, developed HCC. No
      patient with temporal positivity of GGT II developed HCC. The results show that
      GGT II can be applied as an additional marker for HCC, and is valuable not only
      for the diagnosis of clinical HCC, but for the detection of small or subclinical
      HCC. Periodic follow-up with assay of GGT II in patients at high risk for HCC may
      predict the development of hepatoma.

PMID- 1353663
TI  - Expected behavior of conditional linkage disequilibrium.
AB  - The ubiquitousness of RFLPs in the human genome has greatly helped the mapping of
      human disease genes, and it has been suggested that population measures of
      association between disease and marker loci could help with this mapping. For
      rare diseases, random samples are taken from within disease genotypes in order to
      obtain reasonable sample sizes, but this sampling strategy requires a
      modification of the usual measures of association. We present theoretical
      predictions for the mean and variance of such a modified measure, under the
      assumption that the disease gene is maintained at a constant low frequency in the
      population. The coefficient of variation of this modified measure is large enough
      that caution is needed in using the measure to locate disease genes, and,
      furthermore, the coefficient of variation cannot be made arbitrarily small by
      increasing sample size. The modified association measure is calculated for
      recently published data on cystic fibrosis.

PMID- 1353665
TI  - Spondyloepiphyseal dysplasia in a Cape Town family: linkage with the gene for
      type II collagen (COL2A1).
AB  - A moderately severe form of autosomal dominant (AD) spondyloepiphyseal dysplasia
      (SED) has been documented in 14 individuals in 3 generations of a family in Cape
      Town, South Africa. Affected persons had a short trunk; radiographic
      investigations indicated that skeletal involvement was worst in the hips and
      spine. Linkage studies with restriction fragment length polymorphisms (RFLPs)
      associated with the COL2A1 gene and the phenotype yielded a maximal LOD score of
      4.51 at theta = 0.00. This result suggests that the structural locus for type II
      collagen is primarily involved in the pathogenesis of this form of SED.

PMID- 1353664
TI  - Molecular abnormalities of a human glucose-6-phosphate dehydrogenase variant
      associated with undetectable enzyme activity and immunologically cross-reacting
      material.
AB  - Among a large number of glucose-6-phosphate dehydrogenase (G6PD) variants
      associated with different severity of clinical manifestations, enzyme deficiency,
      and kinetic abnormalities found in humans, only one variant exhibits no
      measurable activity and lacks an immunologically cross-reacting material in blood
      cells and other tissues. The mRNA content of the patient's lymphoblastoid cells
      was found to be normal, and the size of mRNA was also normal (i.e., approximately
      2.4 kb). Western blot hybridization indicated that the patient's cells did not
      produce cross-reacting material. The variant mRNA was reverse transcribed and
      amplified by PCR. Nucleotide sequencing of the variant cDNA showed the existence
      of three nucleotide base changes, i.e., a C----G at nucleotide 317 (counting from
      adenine of the initiation codon), which should cause Ser----Cys substitution at
      the 106th position (counting from the initiation Met); a C----T at nucleotide
      544, which induces the Arg----Trp at the 182d position; and a C----T at
      nucleotide 592, which induces Arg----Cys at the 198th position of the protein.
      The existence of three mutation sites was confirmed by sequencing of selected
      regions of the variant gene. No base deletion or frameshift mutation was found in
      the variant cDNA. No nucleotide change was detected in the extended 5' region,
      which included the most distal cap site. When the variant cDNA was expressed in
      Escherichia coli, the G6PD activity was approximately 2% of that expressed by the
      normal cDNA, and cross-reacting material was undetectable. However, when the
      variant mRNA was expressed in the in vitro translation system of rabbit
      reticulocytes, the variant protein was produced. These results suggest that
      extremely rapid in vivo degradation or precipitation of the variant enzyme
      induced by the three amino acid substitutions could be the major cause of the
      molecular deficiency.

PMID- 1353668
TI  - Malignant melanoma: a symposium report. Proceedings of the Third Annual Melanoma
      Conference. St. Petersburg, Florida, March 1991.

PMID- 1353666
TI  - Cytogenetic, biochemical, and molecular analyses of a 22q13 deletion.
AB  - We report on a 3-year-old boy with a terminal deletion of 22q. The activity of
      alpha-N-acetylgalactosaminidase was normal while arylsulfatase A activity was
      reduced. Molecular analysis demonstrated the lack of paternal alleles of D22S45
      and D22S55.

PMID- 1353669
TI  - Potential histamine H2-receptor antagonists: synthesis and pharmacological
      activity of derivatives containing acylamino-furazan moieties.
AB  - Analogues of 3-amino-4-[2-[(5-dimethylaminomethyl-2-furyl)methylthio]ethylamino]
      furazan (1) containing carbonyl groups joined to the amino functions linked to
      the furazan system have been synthetized and investigated for their H2-antagonist
      properties on the isolated guinea pig right atrium. The presence of the carbonyl
      group lowers the activity in respect to the corresponding leads. The decrease in
      activity is only by 1-2 orders of magnitude in the 3-acylamino-furazan series
      versus inactivity in the 4-acylamino isomers and in the diacylated series.

PMID- 1353667
TI  - Iontophoretic study of speed of action of various muscle relaxants.
AB  - The speed of action of nondepolarizing muscle relaxants is inversely related to
      potency. The hypothesis that this effect occurs at the end plate was tested in a
      frog (Rana pipiens) cutaneous pectoris muscle preparation. Brief acetylcholine
      pulses (10-100 ms) were applied iontophoretically from a central barrel of a
      triple-barrelled microelectrode located near an end plate. Long pulses (10-200 s)
      of muscle relaxant (gallamine, rocuronium, d-tubocurarine, atracurium,
      vecuronium, pancuronium, and doxacurium) were applied from one of two other
      barrels. The responses were a voltage change at the end plate, measured with an
      intracellular electrode. To evaluate potency, intracellular voltage changes
      following iontophoretic acetylcholine pulses were measured after application of
      various concentrations of muscle relaxants. The following were the equilibrium
      dissociation constants, which represent concentration of relaxant for 50%
      inhibition of response (mean plus or minus standard deviation): gallamine, 4.56
      +/- 0.44 microM (n = 5); rocuronium, 0.71 +/- 0.09 microM (n = 6); d
      tubocurarine, 0.59 +/- 0.07 microM (n = 4); atracurium, 0.31 +/- 0.03 microM (n =
      4); vecuronium, 0.23 +/- 0.02 microM (n = 5); pancuronium, 0.18 +/- 0.03 microM
      (n = 3); doxacurium, 0.11 +/- 0.03 microM (n = 5). Both onset and offset of
      effect of muscle relaxant proceeded with an exponential time course.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1353670
TI  - Papers presented at the 99th Scientific Session of the Western Surgical
      Association. Colorado Springs, Colorado, November 15-18, 1991.

PMID- 1353671
TI  - Complications following pancreaticoduodenectomy. Current management.
AB  - From 1980 to 1989, 279 patients underwent pancreaticoduodenectomy at a single
      institution with a postoperative mortality of 4%. The aim of this study was to
      determine incidence, origin, and present management strategy of early
      complications following this operation. Significant morbidity occurred in 46% of
      the patients, including delayed gastric emptying (23%), pancreaticojejunal
      anastomotic leak (17%), intra-abdominal sepsis (10%), biliary-enteric anastomotic
      leak (9%), gastrointestinal tract bleeding (5%), and intra-abdominal hemorrhage
      (3%). Complications were associated with advanced age, prolonged operations, and
      increased operative blood loss. Most complications were managed nonoperatively.
      Mortality was increased when a reoperation was required, a biliary-enteric leak
      occurred, or an intra-abdominal abscess developed. Pancreaticoduodenectomy
      continues to carry a high postoperative morbidity; however, operative mortality
      is low, and management of complications has been made simpler with more
      sophisticated, nonoperative therapeutic options.

PMID- 1353672
TI  - Drug-induced movement disorders in institutionalised adults with mental
      retardation: clinical characteristics and risk factors.
AB  - Fifty-three institutionalised adults with mental retardation, the majority
      (73.5%) moderate to severe, were examined for drug-induced movement disorders.
      Using a global AIMS score of 2 or more, 16 (34%) of the 47 subjects who had been
      exposed to neuroleptics had tardive dyskinesia (TD). Three of these had developed
      the dyskinesia upon withdrawal of neuroleptics. The dyskinetic movements were
      mainly seen in the lingual, perioral and other facial muscles. Two (33%) out of 6
      subjects with no history of exposure to neuroleptics also had similar dyskinetic
      movements. The total neuroleptic dose significantly, and age marginally, but not
      sex, brain damage or level of mental retardation, emerged as risk factors for TD.
      Two (3.7%) subjects had definite akathisia and 16 (30.8%) significant
      extrapyramidal side effects. This study supports the findings of previous studies
      of considerable neurological adverse effects of neuroleptics in this patient
      group and cautions against their injudicious use. It provides further evidence
      for some putative risk factors for TD and is noteworthy for its lack of support
      for the contentious issue of brain damage as a risk factor.

PMID- 1353673
TI  - Neuroleptic prescription for Chinese schizophrenics in Hong Kong.
AB  - There are very few studies on the pattern of neuroleptic prescription for
      schizophrenics in Asia. 106 schizophrenic patients in a psychiatric unit of a
      general teaching hospital in Hong Kong were surveyed. The mean daily dose (in
      chlorpromazine equivalent) was low (568.5mg). The mean daily dose of high potency
      agents was four times that of low potency agents. A high frequency of use of
      anticholinergic drugs may indicate that Chinese are more susceptible to acute
      extrapyramidal side-effects.

PMID- 1353674
TI  - Beta-blockers: propranolol, metoprolol, atenolol, pindolol, alprenolol and
      timolol, manifest atherogenicity on in vitro, ex vivo and in vivo models.
      Elimination of propranolol atherogenic effects by papaverine.
AB  - The addition of the beta-blockers propranolol, metoprolol, atenolol, pindolol,
      alprenolol and timolol to a culture of peritoneal macrophages or smooth muscle
      cells induced an increase in the intracellular cholesterol content. Blood serum
      obtained from a rabbit after a peroral administration of beta-blockers also
      induced cholesterol accumulation. This property of drug or blood serum obtained
      after peroral administration is conventionally referred to as atherogenic
      potential or atherogenicity. Regular administration of propranolol during a 21
      day period evoked stable atherogenicity of rabbit blood serum. This was
      accompanied by stimulation of manifestations of atherosclerosis in the aorta
      deendothelialized with a balloon catheter. Propranolol increased neointimal
      thickening, lipid accumulation, an increase in cell number and in the collagen
      content. In vitro, the combination of propranolol with papaverine eliminated the
      atherogenic effect of propranolol which manifested itself as stimulation of
      cholesterol accumulation in cultured cells. Simultaneous peroral administration
      of propranolol and papaverine prevented the appearance of serum atherogenicity.
      Papaverine eliminated neointimal thickening, an increase in cell number and in
      the lipid and collagen contents evoked by propranolol. Papaverine itself had no
      effect on these parameters. Thus, the atherogenicity of propranolol as well as
      capacity of papaverine to eliminate beta-blocker atherogenicity revealed in cell
      culture was confirmed in vivo. We hope that these results may be useful in the
      development of new drugs and optimization of antiatherosclerotic drug therapy.

PMID- 1353675
TI  - Long QT syndrome presenting as a seizure.
AB  - A 21-year-old woman was brought to the emergency department after being found
      unconscious in a hotel lobby. On presentation, she was awake but confused. The
      initial evaluation revealed no evidence of trauma, metabolic abnormality, drug
      ingestion, or intracranial process. The only abnormality noted was
      electrocardiographic, and included a long QT interval as well as occasional
      atrial and junctional beats within a normal sinus rhythm. While in the department
      the patient developed tonic-clonic activity and was concurrently noted to have
      developed ventricular tachycardia. A precordial thump was given with the
      simultaneous cessation of the arrythmia and the seizure. After definitive
      electrophysiologic study, the diagnosis of long QT syndrome was made. Treatment
      consisting of beta blockade and pacemaker insertion prevented further arrythmia
      or seizure activity. Long QT syndrome should be considered a possible etiology in
      any patient presenting with new onset seizures, especially in the young.

PMID- 1353676
TI  - High pressure industrial steam washer injury resulting in digital amputation.
AB  - High pressure washers are increasingly used to clean industrial machinery. We
      report a case of severe full skin thickness burn resulting from momentary
      exposure to the jet of steam.

PMID- 1353677
TI  - Neurologic complications of bacterial meningitis in children.

PMID- 1353678
TI  - Does a subparalysing dose of vecuronium enhance diaphragm fatigue?
AB  - We have examined, in six healthy volunteers, the effect of a subparalysing dose
      of vecuronium on the development of diaphragm fatigue. Vecuronium was given as a
      0.5-mg bolus i.v. followed by 0.5 mg infused over 30 min; as a control, saline
      was given in random order. Diaphragm strength was assessed by measuring
      transdiaphragm pressure and by electromyography. Diaphragm fatigue was induced by
      breathing against an inspiratory resistance. The plasma concentration of
      vecuronium varied between 15 and 30 ng ml-1 15 min after administration of
      vecuronium was started. Peripheral neuromuscular block was not detected in any
      subject. Diaphragm fatigue developed within the same period in both groups: mean
      334 (SD 166) s after saline and 345 (190) s after vecuronium. The
      electromyographic pattern of diaphragm fatigue and the time constant of
      relaxation of transdiaphragm pressure after fatigue were similar in both groups.
      We conclude that, at low plasma concentrations of vecuronium, similar to those
      present in the postoperative period, there was no predisposition to diaphragm
      fatigue.

PMID- 1353679
TI  - Effect of doxapram on neostigmine evoked antagonism of vecuronium neuromuscular
      block.
AB  - We have examined the effect of doxapram on neostigmine-evoked antagonism of
      vecuronium neuromuscular block in a double-blind study in anaesthetized patients.
      Neuromuscular transmission was measured with a Datex Relaxograph. The mean time
      to recovery of the first contraction of the train-of-four (T1) from 25% to 75%
      was significantly longer in the presence of doxapram (138 (SEM 21) s; n = 23)
      than in its absence (95 (13) s; n = 29) (P = 0.014). The recovery of the train-of
      four ratio was prolonged also in the presence of doxapram, although this
      difference was not statistically significant.

PMID- 1353680
TI  - Effect of doxapram on the rate of recovery from atracurium and vecuronium
      neuromuscular block.
AB  - We have studied the effect of doxapram on the rates of spontaneous and
      neostigmine-induced recovery from neuromuscular block with atracurium and
      vecuronium, by measurement of the time to recovery of T1 (first twitch in the
      train-of-four) from 25 to 75% of control (recovery index, RI). After each
      neuromuscular blocking drug, RI was measured without administering either
      doxapram or neostigmine (control group), or after administration of doxapram 1 mg
      kg-1, neostigmine 50 micrograms kg-1 or a combination of doxapram and
      neostigmine, in groups of 10 patients. RI was significantly longer after
      vecuronium in the presence of doxapram compared with control (20.1 min vs 14.6
      min). There was no significant difference in the RI after atracurium in the
      presence of doxapram compared with control (12.5 min vs 11.8 min) or when
      neostigmine was administered with or without doxapram (2.4 min vs 2.4 min,
      respectively after vecuronium; 3.3 min vs 2.9 min, respectively, after
      atracurium).

PMID- 1353681
TI  - Corticosteroids and resistance to vecuronium.

PMID- 1353682
TI  - Stereoselectivity at alpha-adrenoreceptor subtypes: observations with the
      enantiomers of WB 4101 separated through their amides of N-tosyl-(S)-proline.
AB  - We present a chromatographic method for the separation and determination of the
      optical purity of the enantiomers of WB 4101 [(+/-)-1], one of the most potent
      and selective alpha 1-adrenoreceptor antagonists. (+/-)-1 was converted into the
      amide of N-tosyl-(S)-proline. The two diastereoisomers were separated on silica
      gel and analysed by HPLC reversed phase. The analytical method described is both
      accurate and sensitive and allows the optical purity to be determined at very low
      concentrations and to obtain WB 4101 enantiomers with a purity of more than
      99.95%.

PMID- 1353683
TI  - Expression of multidrug resistance gene mdr1 mRNA in a subset of normal bone
      marrow cells.
AB  - The multidrug resistance gene mdr1, encoding P-glycoprotein (P-gp), can be
      expressed at high levels in tumour cells derived from normal tissues with
      constitutive high expression of this gene. In myelogenous leukaemia, the
      incidence of increased expression of mdr1 gene contrasts with the low expression
      of this gene in normal bone marrow (b.m.). To detect cells expressing mdr1 gene
      in normal and post-chemotherapy b.m., we used in situ RNA hybridization and RNA
      phenotyping by the polymerase chain reaction for mdr1 mRNA detection. The
      presence of P-gp was evaluated by immunocytochemistry with MRK16. Fifteen b.m.
      (eight normal and seven post chemotherapy) were tested by in situ hybridization
      and either PCR (three b.m.) or immunocytochemistry (11 b.m.) or both (one b.m.).
      With in situ mRNA hybridization, a subset (7.7% +/- 3.1%) of b.m. cells expressed
      mdr1 mRNA in all cases tested, with no significant differences between normal
      b.m. and post chemotherapy b.m. 18% of myeloid recognizable cells and 7% of the
      cells with lymphoid morphology expressed mdr1 mRNA. By RNA phenotyping, the four
      samples tested for in situ hybridization and two additional post chemotherapy
      b.m. expressed mdr1. MRK16 was unable to detect a significant number of cells
      expressing P-gp either by immunocytochemistry in the 12 b.m. tested for in situ
      hybridization (0% in nine cases; 0.4%, 1% and 3% of positive cells in three
      cases), or by flow cytometry in six additional normal b.m. (0-1.4% positive
      cells).

PMID- 1353684
TI  - Kinetics of dipeptidyl peptidase IV proteolysis of growth hormone-releasing
      factor and analogs.
AB  - The kinetics and selectivity of proteolysis of synthetic human growth hormone
      releasing factor and analogs by purified human placental dipeptidyl peptidase IV
      (DPP IV) were studied by HPLC. The initial rates of Ala2-Asp3 cleavage (pH 7.8,
      37 degrees C, So = 0.15 mM) were all approx. 5 mumol min-1 mg-1 for the parent
      hormone, GRF(1-44)-NH2, and the fragments, GRF(1-29)-NH2 and GRF(1-20)-NH2. Lower
      activities observed for GRF(1-11)-OH, GRF(1-3)-OH, and cyclic lactam analogs
      indicate S1'-Sn' binding. Assays of [Trp6]-GRF(1-29)-NH2 versus [D-Trp6]-GFR(1
      29)-NH2 indicate an S4' binding cavity. Peptides with D-configuration at P2, P1
      or P1' and desNH2Tyr1 and N-MeTyr1 analogs of GRF were not cleaved. Catalytic
      parameters for the P1-substituted analogs [X2,Ala15]-GRF(1-29)-NH2 were found to
      vary with X as follows, Km: Abu less than Ala less than Pro less than Val less
      than Ser less than Gly much less than Leu; kcat: Pro greater than Ala greater
      than Abu greater than Ser greater than Gly much greater than Leu greater than
      Val; kcat/Km: Abu greater than Pro greater than Ala much greater than Ser greater
      than Gly = Val much greater than Leu. Km is at a minimum and kcat/Km at a
      maximum, for a hydrophobic P1 side-chain of about 0.25 nm in length, i.e., the
      ethyl side-chain of alpha-aminobutyric acid (Abu) is very close to optimal. These
      results further define the S1 selectivity of DPP IV and may be useful in the
      design of DPP IV resistant GRF analogs that can be produced by recombinant DNA
      methods and the design of DPP IV inhibitors.

PMID- 1353685
TI  - Identification of transglutaminase substrates in HT29 colon cancer cells: use of
      5-(biotinamido)pentylamine as a transglutaminase-specific probe.
AB  - A biotinamine probe, 5-(biotinamido)pentylamine, was used for biotin-labeling of
      proteins in HT29 colon cancer cell extracts by endogenous transglutaminase
      activity. The biotin-labeled protein substrates were isolated and recovered by
      avidin-affinity chromatography. The proteins were separated using SDS
      polyacrylamide gel electrophoresis, electroblotted onto a polyvinylidene
      difluoride membrane, visualized using Coomassie blue, cut out, and sequenced.
      Amino acid sequence data identified human fructose-1,6-bisphosphate aldolase A,
      an intracellular protein, as a substrate for cellular transglutaminase.

PMID- 1353686
TI  - Retroviral gene therapy and its application in oncohematology.
AB  - A symposium entitled "Foetal and Neonatal Cell Transplantation and Retroviral
      Gene Therapy" recently organized under the aegis of the Merieux Foundation in
      Annecy, France, brought together 100 scientists and clinicians from European
      countries and the United States. The last day of the meeting focused on
      retroviral gene therapy in oncohematology. The speakers provided the basis for
      therapeutic applications of gene transfer and showed practical directions to be
      followed in the near future. Although it may be mainly restricted to in vitro
      manipulation of human cells at start, gene therapy is already applicable to the
      treatment of genetic disorders, cancer, and viral infections. The reality of gene
      therapy was well illustrated by the nature of the questions raised by clinicians
      and scientists during the meeting.

PMID- 1353687
TI  - Mitochondrial DNA polymorphism in dogs.
AB  - Mitochondrial DNA (mtDNA) polymorphism was studied in 20 mongrel dogs using 14
      restriction enzymes. The polymorphism was observed in the cleavage patterns of
      Apa I, EcoR I, EcoR V, Hinc II and Sty I. Three morphs using EcoR I and Apa I and
      two morphs using EcoR V, Hinc II and Sty I were found. However, no polymorphism
      was detected in the cleavage patterns of BamH I, Bgl II, Hae II, Hind III, Pst I,
      Sca I, Stu I and Xba I. The examined dogs were classified in seven types using
      five restriction endonucleases which recognized six nucleotide sequences. The
      value of nucleotide diversity was estimated to be 0.0055. A phylogenetic tree
      constructed by genetic distances among seven restriction types showed at least
      two clusters of mtDNA.

PMID- 1353688
TI  - Endocrine cell populations in the pancreas of diabetic WBN/Kob rats.
AB  - Numerical changes of insulin-, glucagon- and somatostatin-positive cells in the
      pancreas of WBN/Kob male rats with spontaneously occurring diabetes were
      examined. The rats examined were divided into three different age groups: Groups
      I (12 weeks old) and II (33 weeks old) were clinically prediabetic and group III
      (60-90 weeks old) was diabetic. Serum glucose value was in the normal range in
      groups I and II, while it was much higher in group III. B and A cells were
      markedly decreased in number in groups II and III. In group II, the ratio of B to
      A cells was normally preserved, though the total endocrine cell number was
      markedly decreased as compared with that in group I. In group III, the percentage
      of B cells was decreased significantly. The normal ratio in group II seemed to
      keep serum glucose within the normal level. In addition to the total endocrine
      cell reduction, an altered ratio of B and A cells was considered to cause the
      diabetic condition.

PMID- 1353689
TI  - Acid-induced autoagglutination found in chicken pathogenic Escherichia coli
      strain.
AB  - Chicken pathogenic Escherichia coli strains were found to autoagglutinate in a
      static culture of trypticase soy broth (TSB). One strain, designated PDI-386, was
      further studied for its autoagglutinating property. Acidity in the cultured
      medium caused by glucose degradation induced the autoagglutination. The bacterial
      cells grown in a glucose-free L-broth could be aggregated by adding acid, which
      suggests a potentiality of autoagglutination of the strain grown in the L-broth.
      The autoagglutinating parent (Agg) formed small colonies with irregular edges
      like rough colonies on the TS agar, whereas its non-autoagglutinating variant
      (Nag) formed larger smooth colonies with a perfectly round edge. The Nag colony
      was easily generated from the Agg colony on the TS agar. The autoagglutinating
      property was very unstable when the bacteria was passed in the TSB, but rather
      stable in the L-broth. Under electron microscope, the Agg were found to possess
      pili of more than 20 microns in length. However, the phenotypic expression of
      autoagglutination did not correlate with that of mannose-sensitive
      hemagglutination against guinea pig erythrocytes. Incubation of the Nag in the L
      broth at room temperature for more than 10 days provoked the reversion of the
      autoagglutination. There was no difference between the Agg and the Nag in terms
      of surface hydrophobicity, sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) patterns of membrane proteins and LPS, and plasmid
      profiles. The virulence of the Agg was higher than that of the Nag. The
      autoagglutination property is, however, so unstable that the pathogenicity of E.
      coli isolates from chickens should be carefully evaluated.

PMID- 1353690
TI  - Neurobiology and psychopathological states: are we looking in the right place?

PMID- 1353691
TI  - Effect of substituted benzamides on prolactin secretion in the rat.

PMID- 1353693
TI  - The action of interferon alpha on human carcinoid tumours.
AB  - The action of IFN-alpha has been studied in patients with carcinoid tumours. More
      than 300 patients have been treated with IFN-alpha for long periods of time
      (median 2.5 years). IFN-alpha exerts many pleiotrophic effects in carcinoid
      tumours. Antiproliferative effects are manifest mainly by a cell cycle block in
      GO-G1 phase and prolongation of the S-phase. Hormone synthesis is impaired with
      reduced circulating hormone levels after IFN-alpha therapy and the mechanism
      includes reduction of mRNA expression for various hormones. Induction in vitro of
      the nuclear enzyme 2'-5-A synthetase in tumour cells correlates with biochemical
      response and might account for reduced mRNA expression. IFN-alpha induces
      significantly increased intratumoral fibrosis in carcinoid metastases without
      significant changes in tumour size. Finally IFN-alpha causes alteration of the
      major histocompatibility complex (MHC) with increased expression of class I
      antigens on the tumour cells. The net result of all these effects of IFN-alpha is
      an antitumour effect in 70-80% of carcinoid tumour patients with biochemical
      control and abrogated tumour growth for extended periods of time. However, when
      IFN-alpha therapy is withdrawn tumour progression occurs within 3-9 months,
      indicating a controlling but not curing effect.

PMID- 1353692
TI  - Functional analysis of the promoter region of a nodule-enhanced glutamine
      synthetase gene from Phaseolus vulgaris L.
AB  - The 5'-flanking region of gln-gamma, the nodule-enhanced glutamine synthetase
      gene from Phaseolus vulgaris L., has been analysed for cis-regulatory elements
      using a series of 5' deletions and hybrid gln-gamma:: CaMV 35S promoters. The
      promoters were fused to the uidA reporter gene and their activities tested in two
      heterologous expression systems. In the first system, the chimaeric genes were
      transferred to Lotus corniculatus L. using Agrobacterium rhizogenes and their
      expression was studied in nodulated hairy roots. In the second system, the
      constructs were electroporated into tobacco mesophyll protoplasts. The results of
      the 5' deletion analysis showed that the sequence between -597 and -21 (relative
      to the ATG codon) was sufficient for nodule-specific expression of the chimaeric
      gene in nodulated hairy roots, and revealed the existence of at least two
      positive regulatory elements. Sequences located between -2000 and -597 were able
      to stimulate expression in nodules but not protoplasts, while the region from 
      597 to -354 enhanced expression in both nodules and protoplasts. Results obtained
      with the hybrid gln-gamma::35S promoters showed that two overlapping restriction
      fragments (-516/-343 and -474/-293) were able to stimulate expression from a
      heterologous promoter in an orientation-dependent manner. Previous work has
      demonstrated the presence of conserved A/T-rich binding sites for nuclear
      proteins in the region between -516 and -446, and their possible role in
      regulating gln-gamma expression is discussed.

PMID- 1353695
TI  - [Several aspects of the diagnosis of cardiomyopathies and patient management
      policy].

PMID- 1353694
TI  - Genetic linkage analysis in recombinant inbred mice of P40, a putative clone for
      the high-affinity laminin receptor.
AB  - Recombinant inbred (RI) mice were used to genetically map sequences of a 43-kDa
      protein, P40, that was originally identified as a high-affinity laminin receptor.
      More recent data have implicated this protein in development of the retina
      (Rabacchi et al. Development 109: 521-531, 1990), possibly via its proposed
      function in protein translation (G. Brawerman, personal communication). We have
      identified, in Southern blots, a set of P40-related sequences in BXD recombinant
      inbred mouse DNA. Ten restriction fragment length polymorphisms (RFLPs) segregate
      among the RI strains and display strain distribution patterns (SDPs) which are
      linked in varying degrees to previously typed loci on Chromosomes (Chrs) 1, 3, 6,
      9, 11, 14, and 19. An intronic DNA probe from an incompletely processed P40 mRNA
      transcript overlaps with two of these loci mapping near the cholecystokinin gene
      locus on the distal arm of Chr 9 and to another site on the distal arm of Chr 6,
      suggesting that functional genes probably reside at least at these two sites.
      These P40 loci comprise part of a multimember gene family that is well dispersed
      in the mouse genome.

PMID- 1353696
TI  - [Clinico-morphological features of the stomach in subjects who had hemorrhagic
      fever with renal syndrome].

PMID- 1353697
TI  - Synaptic excitation mediated by glutamate-gated ion channels.
AB  - Excitatory synaptic transmission in the central nervous system relies
      predominantly on stimulation of L-glutamate-gated ion channels in postsynaptic
      membranes. Activation of these channels not only mediates millisecond to
      millisecond signalling but can also have long term influences on synaptogenesis
      and synaptic plasticity. Recent work has resolved some longstanding problems
      involving the identity of the transmitter, the postsynaptic localization of the
      receptor subtypes, and the time course of the transmitter in the synaptic cleft.

PMID- 1353698
TI  - Nitric oxide and neurons.
AB  - In the past 2 years powerful evidence has emerged to suggest that nitric oxide
      functions as a neurotransmitter in both the central and peripheral nervous
      systems. Recent evidence suggests that it may play a role in mediating forms of
      synaptic plasticity such as long-term potentiation in the CA1 region of the
      hippocampus, and long-term depression in the cerebellum. Abnormal secretion of
      nitric oxide may be responsible for the neurotoxicity mediated by NMDA receptors
      that results in the pathophysiology of strokes and neurodegenerative diseases.

PMID- 1353699
TI  - Signal transduction and regulation of neurotrophins.
AB  - Our understanding of the molecular nature of neurotrophic interactions has been
      greatly enhanced by the recent isolation and characterization of several new
      neurotrophic factors and their receptors. Neurotrophic factors have been found to
      be regulated by neuronal activity in the central nervous system, and may be
      involved in activity-dependent processes throughout development and maturity.

PMID- 1353700
TI  - Relationship of inherent resistance to doxorubicin, proliferative activity and
      expression of P-glycoprotein 170, and glutathione S-transferase-pi in human lung
      tumors.
AB  - BACKGROUND: This study analyzed whether proliferative activity and expression of
      P-glycoprotein 170 (P-170) or glutathione S-transferase-pi (GST-pi) in human non
      small cell lung carcinomas (NSCLC) represent independent factors in resistance to
      doxorubicin or whether an association exists between these factors. METHODS:
      Thirty-six patients with previously untreated NSCLC participated in the study.
      The thymidine labelling index (TLI) was measured for detection of proliferative
      activity, and immunohistochemistry was used for detection of P-170 and GST-pi.
      The resistance of tumors was determined in vitro by the nucleotide incorporation
      assay. RESULTS: Negative correlations between TLI and P-170 (P = 0.0009) or GST
      pi (P = 0.007) were found. Positive correlations existed between resistance to
      doxorubicin in vitro and P-170 (P = 0.005) or GST-pi (P less than 0.0001).
      Expression of P-170 and GST-pi showed highly significant (P less than 0.0001)
      positive correlation. CONCLUSIONS: The results demonstrate that a significant
      positive relationship between P-170 and GST-pi in NSCLC exists and that the
      expression is increased in resistant tumors and in tumors with a low
      proliferative activity.

PMID- 1353701
TI  - Significance of c-erbB-2 amplification and DNA aneuploidy. Analysis in 78
      patients with node-negative breast cancer.
AB  - BACKGROUND: Amplification of the c-erbB-2 protooncogene and DNA aneuploidy have
      been reported to correlate with poor patient prognosis in human breast cancer.
      Several studies have investigated the prognostic value of these two factors in
      heterogeneous populations of patients with node-positive and node-negative
      disease. This study evaluated, on a series of patients with node-negative
      disease, whether c-erbB-2 proto-oncogene amplification and cellular DNA content
      could identify a subset of patients who, without adjuvant therapy, are destined
      to experience a relapse. METHODS: Paraffin-embedded tissues of 78 patients were
      evaluated for cellular DNA content using flow cytometric analysis. Amplification
      of c-erbB-2 was determined on the same group of patients using slot-blot
      hybridization. The majority of patients were matched with control subjects for
      the following five clinicopathologic criteria: size of primary tumor, menopausal
      status, estrogen receptor, anniversary year of initial treatment, and age at
      treatment. Long-term follow-up (5-16 years) was available for each patient, none
      of whom received any form of adjuvant therapy. RESULTS: The presence of an
      abnormal DNA stemline was found in 47% (37 of 78) of the tissue specimens,
      whereas only 10% (8 of 78) of the tumors expressed from 3-fold to 22-fold c-erbB
      2 amplification. Combined c-erbB-2 amplification and DNA aneuploidy occurred in a
      small group of patients (n = 4), all of whom experienced relapse. The four
      remaining tumors having excessive gene copy numbers had a diploid DNA
      distribution. CONCLUSIONS: The results indicate that tumors that overexpress the
      c-erbB-2 proto-oncogene have variable amounts of DNA and that c-erbB-2
      amplification and DNA ploidy analysis provide limited predictive information of
      relapse in patients with node-negative breast cancer. Although the combination of
      c-erbB-2 amplification and DNA aneuploidy may be a predictor of poor prognosis in
      a small number of patients, neither measurement alone is effective in identifying
      patients at increased risk of recurrence of disease.

PMID- 1353702
TI  - Hormone-regulated apoptosis results from reentry of differentiated prostate cells
      onto a defective cell cycle.
AB  - Castration initiates extensive apoptosis of the secretory epithelial cells lining
      the ducts of the rat ventral prostate, resulting in the striking regression of
      this male sexual accessory tissue. We had previously described the paradox of
      finding similar cascades of gene activity (c-fos greater than c-myc greater than
      hsp-70) induced during the early period of ventral prostate regression and during
      the regrowth of the ventral prostate gland initiated by testosterone
      replenishment. This common pattern of protooncogene expression during periods of
      predominant cellular apoptosis or proliferation caused us to examine further the
      possibility that the two cellular events occur through identical early molecular
      pathways. In the present study we demonstrate that apoptotic prostate epithelial
      cells incorporate bromodeoxyuridine into nuclear high-molecular-weight DNA prior
      to nuclear DNA fragmentation. The DNA synthetic activity occurs in coordination
      with a massive induction of proliferative cell nuclear antigen, a proliferation
      marker, in the nuclei of androgen-deprived prostatic epithelial cells. Moreover,
      this activity is also associated with the increased expression of mRNA encoding
      p53, a suppressor gene well known as a cell cycle-blocking agent. Our data
      indicate that quiescent (G0) prostate epithelial cells undergo apoptosis due to
      two sequential events initiated by testosterone depletion. The first event is the
      active reentry of these cells into the cell cycle. The second event is the
      apoptotic destruction resulting from the inability of the differentiated cells to
      successfully complete this cycle.

PMID- 1353703
TI  - Cytogenetic alterations associated with P-glycoprotein- and non-P-glycoprotein
      mediated multidrug resistance in SW-1573 human lung tumor cell lines.
AB  - Multidrug resistance can be induced in mammalian cells by selection with a single
      cytotoxic agent. Overproduction of the energy-dependent drug efflux pump P
      glycoprotein, encoded by the mdr1 gene, has been identified as the cause of one
      form of multidrug resistance. The molecular basis of other forms of multidrug
      resistance is unknown. Doxorubicin selection of the human squamous lung cancer
      cell line SW-1573 resulted in multidrug-resistant sublines in which a non-P
      glycoprotein-mediated form of multidrug resistance precedes mdr1 expression. Here
      we present a cytogenetic analysis of both non-P-glycoprotein-mediated multidrug
      resistant and P-glycoprotein-mediated multidrug-resistant sublines derived from
      SW-1573. Three independently derived non-P-glycoprotein-mediated multidrug
      resistant sublines showed a heterozygous deletion of the short arm of chromosome
      2 (p23-pter), whereas alterations of chromosome 7 were present in the P
      glycoprotein-mediated multidrug-resistant cell lines. In one series of clonally
      derived P-glycoprotein-mediated multidrug-resistant sublines, mdr1 overexpression
      was accompanied by various markers of chromosome 7 with breakpoints at 7q22, the
      mdr1 gene being known to be located at 7q21.1. Our data suggest that in SW-1573
      cells acquisition of non-P-glycoprotein-mediated multidrug resistance is
      accompanied by a specific deletion or a translocation involving the short arm of
      chromosome 2, whereas in the emergence of P-glycoprotein-mediated multidrug
      resistance a rearrangement of the long arm of chromosome 7 is a critical event.

PMID- 1353704
TI  - Human T-cell leukemia virus type I or a related retrovirus in patients with
      mycosis fungoides/Sezary syndrome and Kaposi's sarcoma.
AB  - Antibodies reactive with human T-cell leukemia virus type I (HTLV-I) proteins
      p19, p24, gp46, p56, and gp68 were detected in four of 27 patients with mycosis
      fungoides/Sezary syndrome (MF/SS) and one patient with Kaposi's sarcoma using
      radioimmunoprecipitation and Western blot analysis. Seroreactivity patterns to
      HTLV-I proteins of MF/SS sera were indeterminate or limited in comparison with
      sera of patients with adult T-cell leukemia/lymphoma. HTLV-I gag- and tax/rex
      specific DNA was demonstrated in peripheral blood from three of the MF/SS
      patients and from the patient with Kaposi's sarcoma by the polymerase chain
      reaction. HTLV-I-specific DNA sequences were not detected in a cohort of seven
      seronegative MF/SS patients. The frequency of HTLV-I infection was four of 27 or
      14.8% among the MF/SS patients, which is several hundredfold higher than in
      normal blood donors. The present data suggest a possible association of HTLV-I or
      a related retrovirus with mycosis fungoides/Sezary syndrome and Kaposi's sarcoma.

PMID- 1353705
TI  - Monoclonal antibody MRK16 reverses the multidrug resistance of multidrug
      resistant transgenic mice.
AB  - Using multidrug-resistant (MDR)-transgenic mice, whose bone marrow cells express
      the human MDR1 gene at a level approximately equal to that found in many human
      cancers, we determined the efficacy of human-specific anti-P-glycoprotein
      monoclonal antibody MRK16 in overcoming multidrug resistance in an intact animal.
      MRK16 alone (2 mg) did not significantly affect the WBC counts of the MDR
      transgenic mice, but MRK16, as well as the F(ab')2 fragments of MRK16, led to a
      dose-dependent circumvention of bone marrow resistance against daunomycin,
      doxorubicin, vincristine, vinblastine, etoposide, and taxol. This sensitizing
      effect could not be enhanced by combining MRK16 with low molecular weight
      chemosensitizing agents such as verapamil, quinine, quinidine, or cyclosporin A.
      We also investigated the concept of specifically targeting and killing multidrug
      resistant cells by using MRK16 coupled to Pseudomonas exotoxin (PE). MRK16-PE
      resulted in a dose-dependent killing of bone marrow cells in MDR-transgenic mice,
      whereas no bone marrow toxicity was observed in normal control mice.
      Administration of excess MRK16 prior to injection of MRK16-PE successfully
      blocked the effect of MRK16-PE. MOPC-PE, a non-MDR-related control monoclonal
      antibody conjugate, did not target and kill multidrug-resistant bone marrow cells
      in MDR-transgenic mice. Thus, these immunological approaches to reversing
      multidrug resistance appear to be both specific and effective.

PMID- 1353707
TI  - Immunoelectron microscopic localization of thiolases, beta-oxidation enzymes of
      an n-alkane-utilizable yeast, Candida tropicalis.
AB  - The location of acetoacetyl-CoA thiolase (T-I) and 3-ketoacyl-CoA thiolase (T
      III), enzymes of the fatty acid beta-oxidation system, was studied in n-alkane
      grown Candida tropicalis cells by immunoelectron microscopy using a post
      embedding method with colloidal gold conjugated IgG. The deposition of gold
      particles for T-I was detected in the microbodies and cytoplasm and that of gold
      particles for T-III specifically in the microbodies. The double labeling
      technique confirmed that T-I and T-III occurred concurrently in a microbody and T
      I also in cytoplasm. These results were consistent with the biochemical data
      based on subcellular fractionation and indicated that the yeast beta-oxidation
      system operates efficiently only in the microbodies.

PMID- 1353706
TI  - Combined antimicrotubule activity of estramustine and taxol in human prostatic
      carcinoma cell lines.
AB  - Estramustine (EM) and taxol, two antimicrotubule agents with distinct and
      apparently opposing mechanisms of action, were found to be effective in
      combination in the preclinical treatment of EM-resistant and sensitive, wild-type
      human prostatic carcinoma cell lines. Estramustine combined with 1 nM taxol
      (concentration 100-fold less than that measured in plasma of patients treated
      with taxol) produced greater than additive effects on the inhibition of cell
      survival of both wild-type and EM-resistant cells. When taxol was used with
      another microtubule-destabilizing drug, vinblastine, no significantly increased
      cytotoxicity was observed. Other effects on wild-type and EM-resistant cells
      produced by the combination of EM and taxol included (a) an increased proportion
      of the cells in the S phase of the cell cycle; (b) no mitotic block; and (c) an
      increase in the percentage of micronucleated cells from a control value of less
      than 1% to greater than 20% after drug treatment. Immunofluorescent microscopic
      analysis of the effect of this drug combination on the mitotic spindle apparatus
      revealed specific examples of aberrant mitotic figures, including multiple
      asters, cells with two distinct spindles, and tripolar spindles able to traverse
      mitosis and complete cytokinesis. These data provide supportive preclinical
      evidence for the potential development of an EM/taxol combination clinical
      regimen either for prostate or other cancers.

PMID- 1353708
TI  - A comparison of esmolol and labetalol for the treatment of perioperative
      hypertension in geriatric ambulatory surgical patients.
AB  - This is an open randomized study comparing the efficacy and safety of i.v.
      esmolol and labetalol in the treatment of perioperative hypertension in
      ambulatory surgery. Twenty-two elderly patients undergoing cataract surgery under
      local anaesthesia were studied. The main inclusion criteria were development of
      systolic blood pressure greater than 200 mmHg or diastolic greater than 100 mmHg.
      Esmolol was given as a bolus 500 micrograms.kg-1 i.v. followed by a maintenance
      infusion (150-300 micrograms.kg-1.min-1). Labetalol was given as a bolus of 5 mg
      i.v. followed by 5 mg increments as needed up to a maximum of 1 mg.kg-1. Esmolol
      and labetalol both produced reductions in systolic and diastolic blood pressure
      (P less than 0.05) within ten minutes of administration which lasted for at least
      two hours. Reduction of blood pressure by esmolol was accompanied by a decrease
      in HR (P less than 0.05). Two patients developed extreme bradycardia (HR less
      than 50 beats.min-1) and esmolol had to be discontinued. Labetalol, in contrast,
      induced only a moderate decrease in HR. None of the patients treated with
      labetalol experienced any prolonged side effects such as orthostatic hypotension.
      In conclusion, esmolol may produce considerable bradycardia in elderly patients
      when hypertension is not accompanied by tachycardia. Labetalol was easier to
      administer in the ambulatory setting and one-tenth the cost of esmolol.

PMID- 1353709
TI  - Enzyme-linked immunosorbent assay of c-erbB-2 oncoprotein in breast cancer.
AB  - Amplification or increased expression of the c-erbB-2 gene has previously been
      reported to be a prognostic marker for breast cancer. Gene amplification is
      usually measured by Southern blotting, whereas increased protein expression is
      usually detected by immunocytochemistry. We measured c-erbB-2 protein with an
      enzyme-linked immunosorbent assay (ELISA). High concentrations of oncoprotein
      were found in 25 of 161 (16%) primary breast cancers and in 3 of 6 (50%) breast
      cancer metastases. High concentrations were not found in normal breast tissue or
      benign breast tumors. In the primary cancers, high concentrations of c-erbB-2
      protein were found more frequently (a) in estrogen receptor-negative tumors than
      in estrogen receptor-positive tumors, (b) in progesterone receptor-negative
      tumors than in progesterone-positive tumors, and (c) in axillary node-positive
      cancers than in node-negative cancers. Patients with tumors containing high
      amounts of the c-erbB-2 protein had a significantly shorter (P less than 0.001)
      disease-free interval and overall survival rate than did patients with low
      amounts. We conclude that assay of c-erbB-2 protein by ELISA is simple, rapid,
      and quantitative and offers important prognostic information in breast cancer.

PMID- 1353710
TI  - Preventive Medicine: Challenges and Opportunities for Clinical Laboratories.
      Proceedings of the 15th annual Arnold O. Beckman Conference on Clinical
      Chemistry. Newport Beach, California, January 19-21, 1992.

PMID- 1353711
TI  - Monoclonal antibody to MALA-2 (ICAM-1) reduces acute autoimmune nephritis in kdkd
      mice.
AB  - Hereditary tubulointerstitial nephritis is a prominent cause of renal failure in
      humans. A variety of animal models utilizing immunologically induced nephritis
      have been developed. The kdkd congenic variant of the CBA/Ca mouse has normal
      kidneys at birth but develops progressive, lethal autoimmune nephritis beginning
      at approximately Week 8. The destruction of renal tubular epithelium in mediated
      by a population of antigen-specific, H-2Kk-restricted, Lyt-2+, L3T4- T cells. The
      present experiments demonstrate that systemic treatment with anti-ICAM-1
      monoclonal antibody reduces kidney disease in kdkd mice. Anti-ICAM-1 mab
      localizes to inflammatory sites in the kidney and effects a significant reduction
      in leukocyte infiltration. Concomitantly, urine protein levels of anti-ICAM-1
      treated mice are significantly reduced. The use of anti-adhesion molecule
      monoclonal antibodies that alter leukocyte activity and/or trafficking may be
      useful therapies for certain autoimmune disorders.

PMID- 1353712
TI  - Effect of anti-CD4 antibody treatment on inflammatory arthritis in MRL-lpr/lpr
      mice.
AB  - MRL-lpr/lpr mice develop an inflammatory arthritis in association with other
      manifestations of autoimmunity. Although a variety of immune cell disturbances
      have been described in these mice, the relationship of these abnormalities to the
      pathogenesis of arthritis has not yet been determined; the role of T cells is
      especially unclear since synovial hypertrophy and joint erosions have been noted
      in some studies in the absence of a significant T cell infiltrate. Therefore, to
      determine if T cells are required for arthritis in MRL-lpr/lpr mice, we evaluated
      the effects of prolonged treatment with a monoclonal anti-CD4 antibody. Knee
      joints from treated mice had markedly reduced arthritis compared to saline
      treated control animals as measured by the degree of synovial hypertrophy and
      inflammation. Nephritis in these mice was concomitantly reduced. In contrast,
      rheumatoid factor levels were not affected by CD4+ cell depletion, despite
      significant effects on anti-DNA. These results indicate that in MRL-lpr/lpr mice
      anti-CD4 therapy can inhibit arthritis, suggesting an important role of T cells
      in the pathogenesis of this lesion.

PMID- 1353713
TI  - Daily chronic headache.

PMID- 1353714
TI  - BASREP: a method for maintaining euglycemia during somatostatin suppression of
      pancreatic secretion.
AB  - A glucagon infusion algorithm has been developed to reestablish basal glycemia
      when pancreatic insulin and glucagon secretion are inhibited by somatostatin
      (SRIF). When insulin alone is infused intraportally during SRIF to replace
      endogenous hormone release, hypoglycemia is generated by the combined actions of
      both peptides. In the presence of SRIF infusion, the normal physiologic response
      to hypoglycemia, i.e. stimulation of glucagon secretion and glucagon-induced
      increase in hepatic glucose production, has been prevented. Our computer
      algorithm, "BASREP", was designed to mimic the normal pancreatic
      counterregulatory response by substituting endogenous alpha-cell secretion with
      exogenous intraportal infusion. Sequential measurements of glucose concentration
      are analyzed with a minimal mathematical model of glucose disappearance, adapted
      to include a variable to describe glucagon stimulation of hepatic glucose
      production. Based upon the observed change in plasma glucose, BASREP computes
      after every sample the infusion rate of glucagon necessary to stimulate glucose
      production and maintain desired glucose level. This method minimizes
      instabilities and should prove useful in future investigations of glucose
      metabolism.

PMID- 1353715
TI  - Akinesia: a syndrome common to parkinsonism, retarded depression, and negative
      symptoms of schizophrenia.
AB  - A distinct hypokinetic syndrome appears to exist across several different
      neuropsychiatric diagnoses, involving (1) slowed motor activity with difficulty
      initiating and sustaining behaviors, (2) anhedonia with depressed mood and
      reduced affective range, and (3) cognitive impairment. Specifically, three well
      recognized states--parkinsonism, retarded depression, and the negative symptoms
      of schizophrenia--prominently feature the components of this syndrome, and
      reduced dopamine turnover in the brain has been hypothesized to play a part in
      the pathophysiology of each. While aspects of this conceptualization remain
      controversial, it generates testable hypotheses that could have implications for
      the understanding and treatment of these states.

PMID- 1353717
TI  - Interaction between corticosteroid and beta-agonist drugs. Biochemical and
      cardiovascular effects in normal subjects.
AB  - The aim of this study was to investigate whether the administration of prednisone
      potentiates any of the acute biochemical and cardiovascular effects of high-dose
      inhaled beta-agonist drugs. These agents are known to cause dose-related changes
      in plasma potassium and glucose, as well as ECG changes in heart rate, corrected
      QT interval (QTc), T wave, and U wave. On theoretical grounds, the concomitant
      use of systemic corticosteroids might enhance these actions. Twenty-four healthy
      subjects were randomized to receive one of three treatments: salbutamol 5 mg or
      fenoterol 5 mg or normal saline solution. Each drug was administered twice, 30
      min apart by nebulizer, and the procedure was repeated after each subject had
      received prednisone 30 mg daily for one week. Plasma potassium and glucose levels
      were measured, and ECGs were obtained after each treatment, together with 12-h
      Holter monitoring for arrhythmias. Changes in plasma potassium and glucose
      following nebulized beta-agonist were significantly greater after treatment with
      prednisone. Baseline potassium level fell from 3.75 mmol/L (95 percent CI 3.61,
      3.89) to 3.50 mmol/L (95 percent CI 3.36, 3.64), and thereafter all values were
      significantly lower at each time point (p = 0.003). The lowest mean plasma
      potassium was obtained 90 min after fenoterol administration with prednisone
      pretreatment: 2.78 mmol/L (95 percent CI 2.44, 3.13). Increases in heart rate and
      QTc interval following both beta-agonist drugs were significant, but T-wave
      amplitude reductions did not reach significance. Prednisone treatment did not
      significantly alter the cardiovascular responses. Supraventricular and
      ventricular ectopic activity was related to beta-agonist use, but no potentiating
      effect was noted following steroid treatment. We conclude that the acute
      biochemical effects of beta-agonist administration are augmented by prior
      treatment with prednisone, but this is not the case for ECG effects. However, the
      degree of hypokalemia noted as a result of this drug interaction may be of
      clinical significance in the hypoxic conditions of acute airways obstruction.

PMID- 1353716
TI  - Akathisia: clinical phenomenology and relationship to tardive dyskinesia.
AB  - Akathisia and tardive dyskinesia (TD) are disorders of movement that are often
      associated with administration of antipsychotic medication. We surveyed 196
      outpatients in a schizophrenia clinic, all receiving antipsychotic medication,
      for the presence of these disorders. Clinical global ratings of akathisia were
      reliable. Akathisia was found in 36% of patients, and TD in 23.5%. Akathisia was
      disproportionately common in patients receiving high-potency neuroleptics. The
      data affirmed recent revisions in the dose-equivalence formulas used with
      fluphenazine decanoate. Akathisia and TD did not seem to be interrelated. Because
      akathisia is common and often limits medication dose and contributes to
      noncompliance, psychiatrists must take this into account when prescribing
      antipsychotic medication.

PMID- 1353718
TI  - Rapid onset of action of inhaled formoterol in asthmatic patients.
AB  - Twelve patients with stable asthma (mean age, 39 years; asthma duration, 11
      years; mean forced expiratory volume in 1 s, 65 percent of predicted; and
      reversibility, 31 percent) were studied in a double-blind crossover trial. The
      patients were studied during three test days. Airway resistance and specific
      airway conductance (Raw and SGaw) were measured using a body plethysmograph and
      pulse rate, blood pressure, tremor, and subjective effects were recorded before
      and 1, 3, 5, 10, 15, 30, 60, and 120 min after the test doses. A baseline Raw
      variability of +/- 20 percent was allowed between the test days. Formoterol 12
      micrograms, 24 micrograms, and terbutaline 500 micrograms were given in a spacer
      (Nebulator) in a randomized double-blind crossover manner as two puffs with a 30
      s interval in between. The effect of formoterol 12 micrograms on Raw was
      significantly better than terbutaline after 3, 5, 10, 60, and 120 min. Formoterol
      24 micrograms was significantly better than terbutaline as soon as 3 min after
      inhalation and at every point in time after that. Formoterol 24 micrograms tended
      to be better than formoterol 12 micrograms but the differences were not
      significant at any point in time. All three treatments were well-tolerated. No
      differences were observed for pulse rate, blood pressure, tremor, or
      palpitations. The overall onset of bronchodilatation after formoterol 12 and 24
      micrograms was faster than after terbutaline 500 micrograms. The tolerability of
      formoterol was good.

PMID- 1353720
TI  - Gold salts and somatostatin: a new combined analgesic treatment for psoriatic
      arthritis.
AB  - In a group of patients affected with psoriatic arthritis the effects of the
      association between gold salts (GS) and somatostatin (SOM), in comparison with
      two groups treated with SOM and GS respectively, were investigated. Sixty
      patients with psoriatic arthritis were selected and randomly allocated in three
      groups of twenty patients each. Group 1 received SOM infusion (250 micrograms/h
      for 96 h) and was assessed at baseline and 1, 15, 30, 60, 90 and 120 days after;
      Group 2 received intramuscular GS and was assessed at baseline, four months
      later, and then every month for four months; Group 3 received GS for 8 months; at
      the fourth month SOM was infused (as in Group 1) and the patients assessed at
      baseline four months later and then as Group 1. Assessment was made with the
      Ritchie index, pain scale and morning stiffness evaluation. Growth hormone was
      assayed in Group 1 every 4 h for 24 h the day before and the day after SOM
      infusion. The association between GS and SOM demonstrated a particular analgesic
      activity, effective on joint pain and tenderness, that lasted for all four months
      of follow-up. SOM showed a good response only after 15 and 30 days, and GS proved
      to be effective at about the sixth month of treatment. Side effects were reported
      in Group 1 (abdominal cramps, mild erythrodermia and supraventricular
      arrhythmia). A growth hormone circadian rhythm was found in psoriatic patients
      both before and after SOM treatment. The beneficial effect of the SOM/GS
      combination is demonstrated in psoriatic arthritis.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1353719
TI  - Variable expression of P-glycoprotein in normal, inflamed, and dysplastic areas
      in ulcerative colitis.
AB  - Screening programs for the detection of cancer in ulcerative colitis are inexact
      and not always successful in finding early, curable cancers. P-glycoprotein is a
      membrane-based, energy-dependent protein found in varying degrees within normal
      human tissue. P-glycoprotein is overexpressed in malignant tumors, particularly
      colorectal cancer, and is known to convey resistance to certain anticancer drugs
      by acting as a membrane "pump." The purpose of this study was to determine the
      expression of this protein in inflamed and premalignant colonic epithelium,
      compare its expression with normal controls, and assess its potential use as a
      screening tool for high-risk patients with ulcerative colitis. Using
      immunohistochemical techniques, the colons of 21 patients (10 with dysplasia)
      with ulcerative colitis were stained with monoclonal antibody C-219 (MAbC219)
      specific for P-glycoprotein. P-glycoprotein was expressed in 38 percent of normal
      areas, 71 percent of inflamed areas (P = 0.0156), and 70 percent of dysplastic
      areas. Comparing the level of expression when progressing from normal to inflamed
      areas within a given patient, 11 patients (52 percent) showed increased
      expression, 8 (38 percent) showed equal expression, and only 2 (10 percent)
      showed decreased expression (P = 0.0225). Comparing expression when progressing
      from inflamed to dysplastic areas (10 patients), 7 showed equal expression and 3
      showed increased expression (P = 0.25). Increasing duration of disease was
      associated with a significant increase in P-glycoprotein expression, but only in
      histologically normal areas. Duration of disease had no effect on P-glycoprotein
      expression in inflamed or dysplastic areas. Similarly, when surgery was performed
      for elective reasons, there was a significant overexpression of P-glycoprotein,
      but only in histologically normal areas. Our findings suggest that the increase
      in P-glycoprotein expression from normal to inflamed and dysplastic areas
      reflects the premalignant nature of ulcerative colitis and occurs early in the
      course of the disease. Further research needs to be done to determine its role in
      cancer surveillance.

PMID- 1353722
TI  - [Long-term therapy after an acute myocardial infarct].

PMID- 1353721
TI  - [The prevention of Pneumocystis carinii pneumonia by pentamidine inhalation].
AB  - 167 HIV-positive patients (155 men, 12 women; mean age 31 [18-61] years) with CD4
      lymphocyte counts below 250/microliter every 4 weeks received 300 mg pentamidine
      per aerosol inhalation during out-patient visits, as prophylaxis against
      Pneumocystis carinii. 89 patients were clinically in the AIDS stage and 33 in the
      AIDS-related complex (ARC) stage. 29 patients had a lymphadenopathy syndrome,
      while 16 were asymptomatic. 130 patients received primary prophylaxis, while 37
      who had previously had an attack of Pneumocystis carinii pneumonia were given
      pentamidine as secondary prophylaxis. During a mean observation period of 8
      months three patients developed Pneumocystis carinii pneumonia (1.7%): their CD4
      lymphocyte count was under 20/microliters. Pentamidine inhalation reduced the
      incidence of a first attack of pneumonia to 0.18% per month and recurrence to
      0.32% per month. These figures confirm the great effectiveness of primary and
      secondary prophylaxis with pentamidine inhalation.

PMID- 1353723
TI  - Lysosomal acid phosphatase is not involved in the dephosphorylation of mannose 6
      phosphate containing lysosomal proteins.
AB  - The mannose 6-phosphate (Man6P) residues that are necessary for the targeting of
      newly synthesized lysosomal proteins are dephosphorylated after delivery of
      lysosomal proteins to lysosomes. To examine the role of lysosomal acid
      phosphatase (LAP) for the dephosphorylation of Man6P residues in lysosomal
      proteins, the phosphorylation of endogenous lysosomal proteins and of
      internalized arylsulfatase A was analyzed in mouse L-cells that overexpress human
      LAP. Non-transfected L-cells dephosphorylate endogenous lysosomal proteins slowly
      (half time approximately 13 h) as well as internalized arylsulfatase A. A more
      than 100-fold overexpression of LAP in these cells did not affect the
      dephosphorylation rate. Control experiments showed that the internalized
      arylsulfatase A and overexpressed LAP partially colocalize and that under in
      vitro conditions purified LAP does not dephosphorylate arylsulfatase A. Taken
      together, these results indicate that LAP is not the mannose 6-phosphatase that
      dephosphorylates lysosomal proteins after their delivery to lysosomes.

PMID- 1353724
TI  - Immunocytochemical evidence for in vitro release of glutamate and GABA from
      separate nerve terminal populations in the rat pontine nuclei.
AB  - A quantitative electron microscopic immunocytochemical method was used to study
      the synaptic handling of glutamate and GABA in slice preparations from the rat
      pontine nuclei. Slices were subjected to a depolarizing stimulus (55 mM K+, 20
      min) in the presence of a physiological or low Ca(2+)-concentration.
      Depolarization at physiological [Ca2+] evoked a depletion of glutamate-like
      immunoreactivity from nerve terminals that contain round vesicles and establish
      asymmetric synaptic contacts. When depolarization was induced in the presence of
      only 0.1 mM Ca2+ (10 mM Mg2+ added), the loss of glutamate was significantly
      reduced or abolished, indicative of a Ca(2+)-dependent component of glutamate
      release. By means of a double-labeling immunocytochemical method we could
      identify a population of nerve terminals that displayed strong GABA-like
      immunoreactivity, and a level of glutamate-like immunoreactivity that was low but
      yet clearly above background level. This type of terminal contains elongated or
      pleomorphic vesicles and establishes symmetric synaptic contacts. In these
      terminals, depolarization evoked a Ca(2+)-dependent depletion of GABA-like
      immunoreactivity, but failed to change the level of glutamate-like
      immunoreactivity. The present study demonstrates that two different types of
      nerve terminal in the rat pontine nuclei contain releasable pools of glutamate
      and GABA, respectively, and that the GABA-releasing terminals also contain a non
      releasable pool of glutamate. The glutamate of the latter pool could act as
      precursor of GABA.

PMID- 1353726
TI  - Correlation of MDR1/P-170 expression with daunorubicin uptake and sensitivity of
      leukemic progenitors in acute myeloid leukemia.
AB  - Prior studies have shown that multidrug resistance gene products may be detected
      in acute myeloid leukemia (AML) cells, and are associated with poor response to
      therapy. We studied whether P-170 expression was associated with in vitro
      daunorubicin (DNR) accumulation and sensitivity of leukemic clonogenic cells (CFU
      L) to DNR in 16 newly diagnosed AML samples. P-170 expression was assessed by
      indirect immunofluorescence using the monoclonal antibody MRK16. DNR cellular
      content was measured by flow cytometry after short incubation with increasing
      concentrations of DNR, and was not correlated with P-170 expression, although
      there was a trend for higher values in P-170-negative samples. The sensitivity of
      CFU-L was studied in a semisolid culture assay by calculating the dose of DNR
      inhibiting the growth of 90% of CFU-L (D90). The D90 was significantly higher in
      P-170-positive than in P-170-negative samples (mean = 1.68 +/- 0.42 microgram/ml
      versus 0.97 +/- 0.35 micrograms/ml respectively, p less than 0.005). Eight of 9
      cases achieving complete remission (CR) after intensive chemotherapy were P-170
      negative, whereas 7 of 7 nonresponders were P-170-positive (p less than 10(-5)).
      D90 was significantly lower for patients achieving CR than for those who did not
      achieve CR (1.12 +/- 0.55 micrograms/ml versus 1.59 +/- 0.37 micrograms/ml, p =
      0.04). It is concluded that P-170 expression is correlated with in vitro
      resistance of clonogenic cells to DNR and may be one mechanism of resistance to
      chemotherapy.

PMID- 1353725
TI  - Locus coeruleus bursts induced by glutamate trigger delayed perforant path spike
      amplitude potentiation in the dentate gyrus.
AB  - Glutamate pressure ejections in the vicinity of locus coeruleus (LC) neurons have
      been shown to produce both short and long-lasting potentiation of perforant path
      (PP) evoked population spike amplitude in the dentate gyrus (DG). These effects
      of LC-glutamate activation resemble those produced by direct application of NE in
      vitro or in vivo. The present study monitored the cellular response of LC neurons
      to local glutamate ejections concomitant with stimulation of the PP evoked
      potential. Double barrel micropipettes or 33 ga cannula-electrode assemblies
      permitted LC unit recording and glutamate ejection at or near the same site in
      urethane anesthetized rats. Glutamate ejections produced a burst of LC activity
      lasting 250-400 ms and followed by a depression of unit activity lasting 4.6 min.
      The maximal spike potentiation produced by LC activation was 158%. The first
      spike to exceed the control range occurred 34 s after the LC burst. Comparable
      silent intervals in LC unit activity induced by systemic clonidine were not
      accompanied by population spike amplitude potentiation. The mean duration of
      potentiation was 4.4 min except in four cases where responses remained
      potentiated for the duration of the experiment. The duration of potentiation was
      not correlated with the termination of LC depression. LC units recovered to
      baseline rates following glutamate induced depression of activity. The occurrence
      of potentiation appeared to require that glutamate activation reach a critical
      number of LC neurons since small glutamate ejections could produce a local burst
      without eliciting potentiation. Long-lasting changes were also related to larger
      glutamate volumes (100 nl).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353727
TI  - Spontaneous conversion of PrPC to PrPSc.
AB  - Octa-repeats of prion proteins (PrP) contain histidine and tryptophan residues
      which are known to function as ligands for transition metals. It is proposed that
      the spontaneous conversion of the PrPC (cellular) isoform into PrPSc (scrapie)
      isoform may be triggered by the coordination of these metals.

PMID- 1353729
TI  - Putative nucleotide binding sites of guinea pig liver transglutaminase.
AB  - Three peptides corresponding to glycine-rich internal sequences of the guinea pig
      liver transglutaminase molecule were synthesized. These were peptide 1 (amino
      acid residues 520-544), peptide 2 (amino acid residues 345-367) and peptide 3
      (amino acid residues 45-69). All of the synthetic peptides demonstrated
      significant binding ability for both ATP and GTP. Peptide 1 was the best
      protector of transglutaminase activity from both ATP and GTP inhibition, while
      peptides 2 and 3 protected the activity only from GTP inhibition. The data shown
      here lead us to propose putative binding site(s) for ATP and GTP guinea pig liver
      transglutaminase.

PMID- 1353728
TI  - Pre-translational regulation by glucocorticoid of fatty acid and
      phosphatidylcholine synthesis in type II cells from fetal rat lung.
AB  - Exposure to fibroblast-conditioned cortisol-containing medium increased fatty
      acid synthase activity and fatty acid synthase, acetyl-CoA carboxylase and ATP
      citrate lyase mRNA abundance in fetal type II alveolar epithelial cells. Both
      fibroblast conditioning and cortisol in the medium were required for maximal
      effect on the mRNA levels, indicating involvement of mesenchymal-epithelial
      interaction in the cortisol effects. The observed effects provide evidence for an
      earlier hypothesis that increased activity of CTP:phosphocholine
      cytidylyltransferase in lung tissue caused by glucocorticoid is due to increased
      fatty acid synthesis. However, evidence suggesting pre-translational regulation
      of this enzyme by glucocorticoid was also found.

PMID- 1353730
TI  - The apical sorting signal on human aminopeptidase N is not located in the stalk
      but in the catalytic head group.
AB  - Human aminopeptidase N carries an apical sorting signal on its ectodomain
      necessary for its correct transport to the apical membrane in Madin-Darby canine
      kidney cells. To determine whether the apical sorting signal is localized in the
      serine/threonine rich stalk or in the catalytic head group, anchor/stalk-minus
      aminopeptidase N, consisting of the hemagglutinin signal peptide and the
      catalytic head group of human aminopeptidase N, was expressed in MDCK cells.
      Anchor/stalk-minus aminopeptidase N was secreted mainly to the apical side. The
      catalytic head group of human aminopeptidase N thus carries an apical sorting
      signal.

PMID- 1353731
TI  - One step purification and characterization of the pyrrolidone carboxyl peptidase
      of Streptococcus pyogenes over-expressed in Escherichia coli.
AB  - Pyrrolidone carboxyl peptidase (EC 3.4.11.8) (Pcp), an enzyme which selectively
      removes pyrrolidone carboxylic acid (PCA) from some PCA-peptides and -proteins,
      was demonstrated in bacteria and in plant, animal and human tissues. In this
      paper we describe the purification to homogeneity of the enzyme of Streptococcus
      pyogenes, over-expressed in Escherichia coli. This was achieved, for the first
      time in one step, by hydrophobic interaction chromatography. Analysis under non
      denaturing conditions revealed a molecular mass of 85 kDa and in the presence of
      sodium dodecyl sulfate gave a molecular mass of 23.5 kDa. Investigations on
      enzymatic properties showed that the Pcp over-expressed in E. coli disclosed
      properties similar to those found for the enzyme extracted from S. pyogenes or
      for some other Pcps studied previously. Thus the over-expressed enzyme should
      serve as a suitable source for N-terminal unblocking prior to some PCA protein
      sequencing.

PMID- 1353732
TI  - Phosphorylated cystatin alpha is a natural substrate of epidermal
      transglutaminase for formation of skin cornified envelope.
AB  - Both keratohyalin granules (KHG) and cornified envelopes were stained
      histochemically in an indirect immunofluorescent study by antiphosphorylated
      cystatin alpha antibody, indicating that phosphorylated cystatin alpha is a
      component of the cornified envelope proteins. When phosphorylated cystatin alpha
      (P-cystatin alpha) was incubated with epidermal transglutaminase (TGase) and Ca2+
      ions, polymerized protein was produced by formation of epsilon-(gamma
      glutamyl)lysine cross-linking peptide bonds between lysine residues of cystatin
      alpha and glutamine residues of suitable protein(s) in the enzyme preparation.
      However, phosphorylated and non-phosphorylated cystatins were polymerized to
      similar extents by the TGase. Immunofluorescent and immunoelectron microscopic
      observations revealed that P-cystatin alpha could be detected in vivo in the KHG
      and cornified envelopes. Treatment of sphingosine, a specific inhibitor of
      protein kinase C, markedly suppressed the incorporation of cystatin alpha into
      KHG. Thus phosphorylation of cystatin alpha by protein kinase C may play an
      important role in targeting cystatin alpha into KHG.

PMID- 1353733
TI  - [A hypothalamic hormone-somatostatin--from endocrinology to neurophysiology].
AB  - The densest distribution of somatostatin (SRIF) neuron perikarya is localized in
      the hypothalamic periventricular nucleus (Pe) close to the third ventricle, from
      which many fibers are projected to the median eminence. The release of SRIF in
      the neurohemal organ into the anterior pituitary modulates GH secretion from
      pituitary somatotrophs. When SRIF input from the hypothalamus to rat anterior
      pituitary is reduced by either neurosurgery or SRIF antiserum iv injection, the
      responsiveness of the pituitaries to human GH releasing factor (hGRF) in an in
      vitro perifusion system is markedly attenuated. Moreover, SRIF pretreatment
      facilitates the GH release response of dispersed anterior pituitary cells to
      hGRF. The long lasting SRIF effect to sensitize somatotrophs appears to take
      place beyond cAMP formation or as an unknown distal effect. These findings
      indicate that SRIF neurons in the Pe play a role in maintaining the pituitary
      responsiveness to GRF in addition to the original action to inhibit GH secretion.
      Neuronal networks between Pe-SRIF neurons, and intra- and extrahypothalamic
      nuclei are identified by Pe stimulation test on GRF-GH secretion. In addition to
      the physiological role in maintaining pituitary responsiveness, Pe SRIF neurons
      have a wide influence on specific SRIF receptor binding in various brain regions
      as well as in the anterior pituitary. Shortly after lesioning the Pe neurons,
      there is a continuous increase in plasma GH level with a transient increase in
      specific binding of 125I-Tyr 11-SRIF-14 to the anterior pituitary. Furthermore,
      there is a similar but a little longer increase in binding of the radioligand to
      some brain areas such as the cerebral cortex, hippocampus, and amygdala nuclei.
      However, neuronal connections between the SRIF neurons and nuclei which are up
      regulated by the lesioning have not been fully proven. When the labeled ligand is
      infused into the lateral ventricle, it is rapidly and widely distributed in many
      periventricular structures in the lateral and third ventricles. These findings
      suggest that SRIF produced in the Pe neurons is transported to other brain areas
      via cerebrospinal fluid in addition to neuronal connections for modulating the
      activity of neurons which have SRIF receptors. Thus, hypothalamic Pe SRIF neurons
      have dualistic roles for controlling anterior pituitary function and modulating
      CNS neuron activity.

PMID- 1353734
TI  - A novel homeobox gene expressed in the anterior neural plate of the Xenopus
      embryo.
AB  - To obtain gene sequences controlling the early steps of amphibian neurogenesis,
      we have performed differential screening of a subtractive cDNA library prepared
      by a novel PCR-based method from a single presumptive neural plate of a Xenopus
      laevis late-gastrula embryo. As a result we have isolated a fragment of a novel
      homeobox gene (named XANF-1, for Xenopus anterior neural folds). This gene is
      expressed predominantly in the anterior part of the developing nervous system.
      Such preferential localization of XANF-1 mRNA is established from its initially
      homogenous distribution in ectoderm of early gastrula. This change in the
      expression pattern is conditioned by a differential influence of various mesoderm
      regions on ectoderm: anterior mesoderm activates XANF-1 expression in the
      overlying ectoderm, whereas posterior axial and ventral mesoderm areas inhibit
      it. The data obtained demonstrate for the first time that selection of genes for
      specific expression in the CNS of the early vertebrate embryo is affected not
      only by chordamesoderm (a neural inductor) but also by ventral mesoderm.

PMID- 1353735
TI  - DNA fingerprinting and analysis of population structure in the chestnut blight
      fungus, Cryphonectria parasitica.
AB  - We analyzed DNA fingerprints in the chestnut blight fungus, Cryphonectria
      parasitica, for stability, inheritance, linkage and variability in a natural
      population. DNA fingerprints resulting from hybridization with a dispersed
      moderately repetitive DNA sequence of C. parasitica in plasmid pMS5.1 hybridized
      to 6-17 restriction fragments per individual isolate. In a laboratory cross and
      from progeny from a single perithecium collected from a field population, the
      presence/absence of 11 fragments in the laboratory cross and 12 fragments in the
      field progeny set segregated in 1:1 ratios. Two fragments in each progeny set
      cosegregated; no other linkage was detected among the segregating fragments.
      Mutations, identified by missing bands, were detected for only one fragment in
      which 4 of 43 progeny lacked a band present in both parents; no novel fragments
      were detected in any progeny. All other fragments appeared to be stably
      inherited. Hybridization patterns did not change during vegetative growth or
      sporulation. However, fingerprint patterns of single conidial isolates of strains
      EP155 and EP67 were found to be heterogenous due to mutations that occurred
      during culturing in the laboratory since these strains were first isolated in
      1976-1977. In a population sample of 39 C. parasitica isolates, we found 33
      different fingerprint patterns with pMS5.1. Most isolates differed from all other
      isolates by the presence or absence of several fragments. Six fingerprint
      patterns each occurred twice. Isolates with identical fingerprints occurred in
      cankers on the same chestnut stems three times; isolates within the other three
      pairs were isolated from cankers more than 5 m apart. The null hypothesis of
      random mating in this population could not be rejected if the six putative clones
      were removed from the analysis. Thus, a rough estimate of the clonal fraction of
      this population is 6 in 39 isolates (15.4%).

PMID- 1353736
TI  - Effect of wing scalloping mutations on cut expression and sense organ
      differentiation in the Drosophila wing margin.
AB  - A number of wing scalloping mutations have been examined to determine their
      effects on the mutant phenotype of cut mutations and on the expression of the Cut
      protein. The mutations fall into two broad classes, those which interact
      synergistically with weak cut wing mutations to produce a more extreme wing
      phenotype than either mutation alone and those that have a simple additive effect
      with weak cut wing mutations. The synergistically interacting mutations are
      alleles of the Notch, Serrate and scalloped genes. These mutations affect
      development of the wing margin in a manner similar to the cut wing mutations. The
      mutations inactivate the cut transcriptional enhancer for the wing margin
      mechanoreceptors and noninnervated bristles and prevent differentiation of the
      organs. Surprisingly, reduction of Notch activity in the wing margin does not
      have the effect of converting epidermal cells to a neural fate as it does in
      other tissues of ectodermal origin. Rather, it prevents the differentiation of
      the wing margin mechanoreceptors and noninnervated bristles.

PMID- 1353737
TI  - Epistasis and the genetic divergence of photoperiodism between populations of the
      pitcher-plant mosquito, Wyeomyia smithii.
AB  - Parallel crosses between each of two southern (ancestral) and one northern
      (derived) population of the pitcher-plant mosquito, Wyeomyia smithii, were made
      to determine the genetic components of population divergence in critical
      photoperiod, a phenological trait that measures adaptation to seasonality along a
      climatic gradient. Joint scaling tests were used to analyze means and variances
      of first- and second-generation hybrids in order to determine whether nonadditive
      genetic variance, especially epistatic variance, contributed to divergence in
      critical photoperiod. In both crosses, digenic epistatic effects were highly
      significant, indicating that genetic divergence cannot have resulted solely from
      differences in additively acting loci. For one cross that could be tested
      directly for such effects, higher order epistasis and/or linkage did not
      contribute to the divergence of critical photoperiod between the constituent
      populations.

PMID- 1353738
TI  - A genetic map of the mouse suitable for typing intraspecific crosses.
AB  - We report the construction of a genetic linkage map of the mouse, consisting
      entirely of genetic markers that can be rapidly typed by polymerase chain
      reaction and that show a high degree of polymorphism among inbred laboratory
      strains. Specifically, the map contains 317 simple sequence length polymorphisms
      at an average spacing of 4.3 cM and is detectably linked to approximately 99% of
      the mouse genome. In typical crosses between inbred laboratory strains, about 50%
      of the markers are polymorphic, making it straightforward to follow inheritance
      in almost any cross.

PMID- 1353740
TI  - The Ustilago maydis pyr3 gene: sequence and transcriptional analysis.
AB  - The pyr3 gene of Ustilago maydis encodes a 391-amino acid (aa) polypeptide. The
      sequence has identifies with dihydro-orotases (DHOases) from other organisms, but
      is most related to sequences of other monofunctional enzymes. The polypeptide
      contains the three domains conserved in other DHOases. The polypeptide encoded by
      the pyr3-1 allele has an aa change seven residues away from the C-terminal
      conserved domain. Transcription start point (tsp) is 58 nucleotides upstream from
      the start codon, and is in a region characterised by CTTT and CATC motifs. In the
      absence of TATA and CAAT boxes, these motifs might be important in
      transcriptional regulation. Gene disruption experiments suggest that the pyr3
      gene product might have another function in addition to that in pyrimidine
      biosynthesis.

PMID- 1353739
TI  - Transition from rapid processive to slow nonprocessive polyadenylation by
      vaccinia virus poly(A) polymerase catalytic subunit is regulated by the net
      length of the poly(A) tail.
AB  - The mRNA of vaccinia virus, like that of eukaryotes, possesses a poly(A) tail.
      VP55, the catalytic subunit of the heterodimeric vaccinia virus poly(A)
      polymerase, was overexpressed and purified to near homogeneity. VP55
      polyadenylated a 30-mer primer representing the 3' end of a vaccinia virus mRNA
      bimodally: 30-35 adenylates were added in a rapid, processive, initial burst,
      after which polyadenylation decelerated dramatically and became nonprocessive.
      Polyadenylation of variants of the 30-mer primer, which contained preformed 3'
      oligo(A) extensions, showed that the transition between the two modes of
      polyadenylation was regulated by the net length of the 3'-oligo(A) tail rather
      than the number of adenylate additions catalyzed by VP55. Primers comprising
      oligo(A) alone were polyadenylated only if they were greater than 34 nucleotides
      in length and, then, only in the slow nonprocessive mode. These data support a
      dynamic model whereby the mode of polyadenylation by VP55 is regulated by
      sequences within the 3' 30-35 nucleotides of the mRNA: Polyadenylation is rapid
      and processive until a net 3'-oligo(A) length of 30-35 nucleotides is achieved.
      Consistent with this, excess oligo(A) did not compete with the 30-mer primer for
      rapid processive polyadenylation. The primer specificity of VP55 may contribute
      to the selective polyadenylation of newly formed mRNA.

PMID- 1353741
TI  - Sulphasalazine induced renal failure.
AB  - Two men with longstanding ulcerative colitis who were treated with sulphasalazine
      for several years and who developed chronic renal failure are reported. Renal
      biopsy specimens showed histological changes consistent with drug induced chronic
      intestinal nephritis. Extensive investigation made other causes of chronic renal
      failure unlikely. One of these patients underwent renal transplantation, the
      other has impaired but stable renal function.

PMID- 1353743
TI  - Effect of aminophenols (5-ASA and 4-ASA) on colonic interleukin-1 generation.
AB  - The effect of 5-ASA and 4-ASA, drugs used for the treatment of inflammatory bowel
      disease, on modulation of experimental colitis and on colonic generation of
      interleukin-1 was evaluated. Three weeks of treatment with 5-ASA or 4-ASA (50
      micrograms/kg) and one week of treatment with 5-ASA significantly decreased
      colonic interleukin-1 generation and the extent and severity of inflammation in a
      rat model of colitis induced by trinitrobenzene sulphonic acid. Colonic biopsies
      were obtained from patients with active ulcerative colitis and organ cultured 24
      hours in the absence or presence of the following drugs: sulphasalazine,
      sulphapyridine, 5-ASA and 4-ASA (25-100 micrograms/ml). Interleukin-1 content in
      tissue cultured in the presence of 5-ASA (100 micrograms/ml) was two-thirds of
      its content in tissue cultured in drug free medium and its release into the
      medium was decreased by 50%. Sulphasalazine 50 micrograms/ml significantly
      decreased by 33% the tissue content but did not affect interleukin-1 release and
      a higher dose was not more effective. Sulphapyridine and 4-ASA in doses up to 100
      micrograms/ml did not affect either interleukin-1 colonic content or its release
      into the culture medium. We conclude that pharmacological suppression of colonic
      interleukin-1 generation may be one, although not the sole mechanism to explain
      the therapeutic efficacy of 5-ASA in the treatment of inflammatory bowel disease.

PMID- 1353742
TI  - Treatment of ulcerative colitis with fish oil supplementation: a prospective 12
      month randomised controlled trial.
AB  - The effect of fish oil on the course of ulcerative colitis was investigated in a
      randomised blinded controlled study. Eighty seven patients received supplements
      of 20 ml HiEPA fish oil as triglyceride (4.5 g of eicosapentaenoic acid) or olive
      oil placebo daily for one year. The oils were given in addition to standard drug
      therapy and trial entry was stratified for disease activity. Fish oil
      significantly increased the eicosapentaenoic acid content of rectal mucosa to
      3.2% of total fatty acids at six months, compared with 0.63% for patients on
      olive oil. This was associated with increased synthesis of leukotriene B5, and
      53% suppression of leukotriene B4 synthesis by ionophore--stimulated neutrophils.
      Leukotriene B4 suppression persisted for at least two months after treatment was
      stopped. Treatment with fish oil resulted in measurable, but only limited
      clinical benefit. For patients entering the trial in relapse (n = 53), there was
      a significant reduction in corticosteroid requirement after one and two months
      treatment. There was a trend towards achieving remission (off corticosteroids)
      faster in the patients on fish oil, although differences were not significant.
      For patients in remission at trial entry or during the trial (n = 69), there was
      no significant difference in the rate of relapse by log rank analysis. We
      conclude that fish oil supplementation produces a modest corticosteroid sparing
      effect in active disease, but there is no benefit in maintenance therapy.

PMID- 1353744
TI  - [Effects of ifenprodil on the adenosine triphosphatase of guinea pig liver
      mitochondria].
AB  - The effects of ifenprodil on adenosine triphosphatase (ATPase) activity were
      examined using guinea pig liver mitochondria. 1) Intact mitochondrial ATPase
      activity was stimulated by ifenprodil in a concentration-dependent manner, this
      effect being further potentiated with dinitrophenol. The stimulation by
      ifenprodil appeared with only ATP among four nucleotides as substrate. Mg2+ and
      Ca2+ attenuated the effect of ifenprodil. Ifenprodil abolished the KCN-induced
      inhibition. 2) Heat-treated mitochondrial ATPase activity, kept for 60 min at 50
      degrees C, was decreased in a concentration-dependent manner by ifenprodil. The
      inhibitory effect of ifenprodil was abolished by Mg2+ and Ca2+. These results
      indicate that ifenprodil has two behaviors, acceleration of a latent ATPase and
      inhibition of an activated ATPase. These findings, together with our previous
      data, suggest that ifenprodil seems to affect the actions of Mg2+ and Ca2+ on
      mitochondrial ATPase by directly affecting the membrane, and these mechanisms may
      be involved in its anti-cyanide effect.

PMID- 1353745
TI  - [Pharmacologic profile of urapidil. Consequences for use as an antihypertensive
      drug].
AB  - Urapidil, a phenylpiperazine-substituted derivative of uracil, is an example of
      an anti-hypertensive which lowers elevated blood pressure via at least two
      different mechanisms. As such, it belongs to the multifactorial or hybrid anti
      hypertensives. Urapidil is a peripherally acting alpha 1-adrenoceptor antagonist,
      and, in this regard, is comparable with prazosin and its successor compounds
      (e.g. doxazosin). In addition, urapidil lowers elevated blood pressure via a
      central mechanism which is new and differs from that of the classical
      antihypertensives with a central nervous effect (clonidine, etc.). This
      additional mechanism favourably influences the side effect profile of urapidil.

PMID- 1353746
TI  - [Another AIDS drug. Azidothymidine--dideoxycytidine].

PMID- 1353747
TI  - [Compliance in therapy of schizophrenic patients with neuroleptics--an overview].
AB  - In connection with the efforts to improve the prophylaxis against relapse in
      schizophrenic patients, the topic of non-compliance to therapy with neuroleptics
      is gaining interest in scientific research. The importance of this problem has
      been underestimated in the past. Starting with a review of the current state of
      research, the article provides an overview of the various determinants of
      compliance. The conclusions made are discussed in terms of optimizing therapy
      possibilities. Central to this point are less psychopharmacological options but
      more process- related aspects of the doctor/patient relationship. Fully informed
      consent of the patient is aimed at; providing him with detailed information on
      the purposes and the side-effects of neuroleptic therapy is discussed in terms of
      its consequences regarding compliant behaviour.

PMID- 1353748
TI  - Monoclonal antibody OPD4 detects neoplastic T cells but does not distinguish
      between CD4 and CD8 neoplastic T cells in paraffin tissue sections.
AB  - Monoclonal antibody (MoAb) OPD4, reported to preferentially react with benign CD4
      T cells in formalin-fixed tissue sections, was examined for its reactivity with
      56 T-cell neoplasms after formalin or Bouin's fixation to determine if it also
      preferentially detects neoplastic CD4 T cells in paraffin tissue sections.
      Monoclonal antibody OPD4 did not preferentially detect neoplastic CD4 T cells,
      since it reacted with 22 of 38 (58%) CD4-positive compared with nine of 14 (64%)
      CD4-negative T-cell neoplasms. However, MoAb OPD4 appears to detect neoplastic T
      cells in Bouin's-fixed (11 of 20 cases [55%]) about as well as in formalin-fixed
      (20 of 32 cases [63%]) tissues. Since MoAb OPD4 does not preferentially react
      with neoplastic CD4 T cells, the utility of this MoAb as a pan-T-cell marker in
      routinely processed tissues was also explored and compared with that of Leu-22,
      UCHL-1, and CD3. All four antibodies reacted with approximately the same
      percentage of T-cell malignancies (51% to 57%). However, examination of different
      clinicopathologic groups and types of fixative highlighted differences.
      Monoclonal antibodies OPD4 and Leu-22 reacted with 62%, while CD3 detected only
      41% of formalin-fixed, postthymic T-cell neoplasms. OPD4, UCHL-1, and CD3 each
      reacted with 55%, but Leu-22 recognized only 45% of Bouin's-fixed, postthymic T
      cell malignancies. OPD4 reacted with none, but CD3 reacted with all four T-cell
      lymphoblastic lymphomas. Various antibody combinations were examined to determine
      an optimal panel for the recognition of T-cell neoplasms in paraffin sections.
      The combination of MoAbs OPD4 and Leu-22 detected 86% of postthymic T-cell
      neoplasms in formalin-fixed tissue sections. Furthermore, MoAb OPD4 appears to be
      relatively specific for T-cell neoplasms, detecting 31 of 56 (55%) T-cell
      malignancies, while only reacting with two of 39 (5%) B-cell neoplasms.
      Therefore, while not preferentially reactive with neoplastic CD4 T cells, MoAb
      OPD4 may be useful as a pan-T-cell marker of postthymic T-cell neoplasms in
      routinely processed, formalin-fixed tissues, especially when used in conjunction
      with MoAb Leu-22.

PMID- 1353749
TI  - Identification of novel human T-cell receptor V beta gene segments by the
      anchored-polymerase chain reaction.
AB  - We have studied the diversity of the expressed human T-cell receptor (TCR) beta
      chain repertoire by analysis of mRNA from unstimulated peripheral blood T-cells.
      The anchored-polymerase chain reaction (PCR) was used to isolate TCRB
      transcripts. Of 20 full or near full-length functional transcripts sequenced, two
      were novel TCRVB gene segments. They have strong sequence similarities to the
      known TCRBV5, and 8 subfamilies. Southern blot analysis and sequence-specific
      oligonucleotide hybridization confirmed: a) that these sequences are present in
      genomic DNA; b) their relationship to the known TCRBV families. A TCRBV sequence
      similar to a recently identified novel TCRBV24 subfamily was also found. We show
      by southern blotting that this sequence forms a single member subfamily, and by
      deletion analysis of T-cell lines, we have mapped this sequence to lie between
      the genes which encode the TCRBV8.1 and TCRBV5.3 gene segments. The results show
      that the anchored PCR is a powerful tool in the analysis of the TCR repertoire,
      which may contain more V gene segments than previously defined.

PMID- 1353750
TI  - Efficacy and effects on pulmonary function tests of weekly 600 mg aerosol
      pentamidine as prophylaxis against Pneumocystis carinii pneumonia.
AB  - A prospective study was designed to evaluate the efficacy and effects on
      pulmonary function tests of weekly 600 mg aerosolised pentamidine as prophylaxis
      against Pneumocystis carinii pneumonia (PCP) amongst two groups of patients
      infected with the human immunodeficiency virus. Group 1 (primary prophylaxis)
      consisted of patients with either diseases indicative of AIDS other than PCP or
      whose absolute CD4 positive lymphocyte count was below 200/mm3, and Group 2
      (secondary prophylaxis) comprised patients with previous proven episodes of PCP.
      Fifty-five patients (30-Group 1, 25-Group 2) were studied over a period of 36
      months, and no patients reached a study end point of either relapse or death due
      to PCP after a mean duration of treatment of 14.9 months (range 9-36 months).
      There were no significant differences between the pulmonary function tests
      (forced expiratory volume in the first second, forced vital capacity and carbon
      monoxide diffusion capacity) performed at the start and end of the study on both
      groups of surviving patients. Ten patients (18%) reported coughing and eight
      patients (15%) were documented to have bronchoconstriction, which was found to be
      preventable by prior administration of disodiumcromoglycate. The results showed
      that weekly 600 mg aerosolised pentamidine is effective and well tolerated for
      primary and secondary prophylaxis against PCP without additional adverse effects.
      Further prospective randomized trials are needed to determine whether doses
      higher than the current recommended 300 mg monthly dosage of aerosolised
      pentamidine provide more efficacy before such an alternative prophylactic
      treatment is generally adopted for patients who cannot tolerate other systemic
      agents.

PMID- 1353751
TI  - Pancreaticojejunostomy and pancreatic leakage after pancreaticoduodenectomy.
AB  - Some techniques of pancreaticojejunostomy have been introduced with reference to
      pancreatic leakage from the pancreaticojejunal anastomosis. Pancreatic leakage
      (+/- ) occurred in 21.4% of pancreaticojejunostomy patients and pancreatic
      leakage (+) in 9.5%. The frequency of pancreatic leakage tended to be higher in
      cases where the pancreatic duct was undilated and the remaining distal segment of
      the pancreas had a soft tissue. Pancreatic leakage led to secondary complication
      in none of the patients in our series, but further technical refinement of
      pancreaticojejunostomy is warranted to reduce the frequency of pancreatic leakage
      to zero.

PMID- 1353753
TI  - Novel complications with HTLV-1-associated myelopathy/tropical spastic
      paraparesis: interstitial cystitis and persistent prostatitis.
AB  - Lower urinary symptoms associated with HTLV-1-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP) are common, but have been regarded as 'neurogenic'
      due to spinal involvements. However, in some cases, these symptoms are
      persistent, progressive, and not directly correlated with the severity of other
      neurologic symptoms of the lower spinal cord. These findings prompted us to
      locate organic lesions in the lower urinary tract and to correlate them with HTLV
      1 infection. Among 35 HAM patients with lower urinary symptoms, we found 4 cases
      with the symptoms persistent and progressive: 3 with contracted bladder and
      another with persistent prostatitis. Histological or cytological examinations
      indicated local lymphocytic infiltrations in the lower urinary tract in all
      cases: 3 by the infiltration in the bladder and the other by a high concentration
      of lymphocytes in expressed prostatic secretions. Of 3 cases whose urinary
      samples were available, 2 showed significant increase in the concentration of
      urinary anti-HTLV-1 antibody of IgA class. The urinary IgA antibody of the third
      case was not elevated, but the sample had been obtained after resection of the
      affected bladder. None of the control cases showed significant anti-HTLV-1 IgA
      antibody in urine except for a case of gross hematuria due to chemotherapy
      directed against adult T-cell leukemia. We suggest inclusion of these processes
      into the spectrum of complications for HAM/TSP. The elevated excretion of anti
      HTLV-1 of IgA class in urine may be an indicator of these complications.

PMID- 1353752
TI  - In vitro anti-tumor activity of anti-c-erbB-2 x anti-CD3 epsilon bifunctional
      monoclonal antibody.
AB  - With the aim of developing an effective cancer immunotherapy for common
      epithelial cancer, a new class of bifunctional antibody (BFA) was developed; one
      arm of this BFA recognized c-erbB-2 gene product, and the other arm recognized
      CD3 epsilon, a T-cell specific surface antigen. Application of this BFA with
      human peripheral blood lymphocytes exhibited specific anti-tumor activity in
      vitro on a breast tumor cell line, ZR-75-1, which expressed abundant c-erbB-2
      gene product on its cell surface. These results indicate that BFA recognizing an
      oncogene product on cell surface is a potential new agent for cancer
      immunotherapy.

PMID- 1353756
TI  - The changing pattern of the splenic lymphocyte subsets in tumor-bearing mice
      after oral treatment with OK-432.
AB  - The aim of this study was to investigate the influence of oral administration of
      OK-432 on the tumor growth of tumor-bearing mice. In addition, the changing
      pattern of the splenic lymphocyte subsets of tumor-bearing mice was evaluated by
      flow cytometry. OK-432 at a dose of 0.1, 1 or 10 KE was administered orally every
      3 days or every other day for 30 days to subcutaneously Meth A tumor-inoculated
      mice. The tumor growth was significantly inhibited in the 1 KE every 3 days
      group, in the 1 KE every other day group and in the 10 KE every 3 days group. In
      the 10 KE every other day group, OK-432 inhibited the tumor growth on days 10 and
      20, while the agent did not show a marked inhibitory effect on day 30. The
      percentages of splenic L3T4-positive cells and splenic asialo GM1-positive cells
      were significantly increased in the 1 KE every other day group, while the
      Lyt2+/Thy1.2+ ratio was decreased. On the other hand, in the 10 KE every other
      day group, OK-432 showed no effect on the percentages of splenic L3T4-positive
      cells and Lyt2+/Thy1.2+ ratio on days 20 and 30. Our results suggest that the
      antitumor effect of oral administration of OK-432 may be correlated with the
      changing pattern of L3T4-positive cells and Lyt2+/Thy1.2+ ratio.

PMID- 1353755
TI  - Effector cell analysis of human multidrug-resistant cell killing by mouse-human
      chimeric antibody against P-glycoprotein.
AB  - A mouse-human chimeric monoclonal antibody (mAb), MH162, against P-glycoprotein
      was previously found to be more effective than an all-mouse mAb (MRK16) in lysis
      of multidrug-resistant (MDR) tumor cells by blood mononuclear cells. The present
      study was performed to identify the effector cells responsible for the chimeric
      mAb-dependent cell-mediated cytotoxicity (ADCC) against MDR cells. The ADCC
      reaction was assessed by a 6-h 51Cr release assay. Highly purified lymphocytes
      (greater than 99%), monocytes (greater than 99%) and neutrophils (greater than
      96%) were obtained from peripheral blood of the same healthy donors. A comparison
      of these three effector cell populations showed no difference between MH162 and
      its all-murine counterpart MRK16 in MDR cell lysis by monocytes or neutrophils.
      But MH162 was more effective than MRK16 in lymphocyte-mediated lysis of the MDR
      cells. The lymphocytes responsible for this ADCC had CD16+ Fc receptors.
      Pretreatment of monocytes with colony-stimulating factors (IL-3, GM-CSF and M
      CSF) caused significant increase in their MH162-mediated lysis of MDR cells.
      Another anti-P-glycoprotein chimeric mAb (MH171) was also more effective than its
      murine counterpart MRK17 in lymphocyte-mediated lysis of MDR cells. These
      findings suggest that mouse-human chimeric mAbs may be useful therapeutically for
      in vivo destruction of MDR cancer cells by the ADCC reaction.

PMID- 1353757
TI  - Skeletal muscle protein metabolism and serum growth hormone, insulin, and
      cortisol concentrations in growing steers implanted with estradiol-17 beta,
      trenbolone acetate, or estradiol-17 beta plus trenbolone acetate.
AB  - Skeletal muscle protein degradation, measured by urinary N tau-methylhistidine
      excretion, and circulating concentrations of growth hormone (GH), insulin (INS),
      and cortisol (CT) were monitored in steers before and after implantation with
      estradiol-17 beta (E2; 24 mg) and trenbolone acetate (TBA; 300 mg). Yearling
      crossbred steers (n = 43) were randomly assigned to four treatment groups in a 2
      x 2 factorial arrangement: nonimplanted controls (C); TBA; E2; and TBA plus E2
      (TBA+E2). A subgroup (Block 1) of 16 steers was bled on d -12, 31, and 72 after
      implanting. Deposition of skeletal muscle protein was markedly increased (P less
      than .001) by E2 and TBA+E2 treatment. This response occurred mainly within the
      first 40 d after implantation and declined (P less than .001) in concert with
      decreasing (P less than .01) concentration of serum E2. Anabolic steroid
      treatment did not affect the rate of skeletal muscle protein breakdown. There was
      no apparent relationship between reduced serum CT concentration (linear effect; P
      less than .01) in TBA-treated steers and skeletal muscle protein degradation
      rate. Blood concentration and pulse activity of INS were not affected by anabolic
      steroid administration. Both TBA- and TBA+E2-implanted steers displayed a linear
      decrease (P less than .05) in serum GH concentration over time, which was similar
      to C. Lowered mean GH concentration resulted from a reduction (TBA main effect; P
      less than .05) in pulse amplitude of GH. Unlike TBA, TBA+E2, and C, only E2
      maintained serum GH concentrations over time. Although increased muscle protein
      deposition was evident in TBA+E2-treated steers, an obvious causal relationship
      between this response and circulating GH, INS, and CT was not revealed. These
      results do not support the concept that combined androgenic agent and estrogen
      administration effectively reduce bovine muscle protein degradation by static
      modulation of circulating endogenous anabolic and antianabolic hormones.

PMID- 1353754
TI  - Activation of the mouse proliferating cell nuclear antigen gene promoter by
      adenovirus type 12 E1A proteins.
AB  - A plasmid carrying the 5'-flanking region (-1584 to +47 with respect to the
      transcription initiation site) of the mouse proliferating cell nuclear antigen
      (PCNA) gene was fused with the chloramphenicol acetyltransferase (CAT) gene, and
      then cotransfected into mouse N18TG2 cells with expression plasmids for the
      adenovirus type 12 E1 genes. Expression of E1A gene products elevated the CAT
      expression by 5- to 9-fold, but expression of the E1B gene product did not. RNase
      protection analysis revealed that the activation of the PCNA gene promoter by E1A
      was at the transcription step. Both the 13S E1A and the 12S E1A activated the
      PCNA gene promoter, indicating that the activation domain of E1A resides in a
      common region(s) of 13S and 12S E1A products. The major target region of E1A was
      mapped within the 68 base-pair region (-21 to +47) of the PCNA gene, which
      includes consensus sequences for transcription factors PEA3 and E2F, although the
      upstream region (-83 to -21) including ATF(CREB)-binding consensus had an
      additional effect in the transactivation.

PMID- 1353758
TI  - Further studies on some physical and biochemical characteristics of
      asaccharolytic pigmented Bacteroides of feline origin.
AB  - The ultrastructure of the appendages of 24 strains of asaccharolytic pigmented
      Bacteroides spp. of cats was studied by transmission electron microscopy. All
      strains examined by thin section showed abundant fimbriae, outer membrane
      vesicles and capsules. Negative staining showed fimbriae which varied from long,
      fine and wavy in Bact. salivosus and cat Group 2 to shorter, less abundant and
      thicker fimbriae in cat strains of Bact. gingivalis as well as type strains of
      Porphyromonas gingivalis and P. asaccharolytica. Capsular material was very thick
      amorphous in human P. gingivalis, cat strains of Bact. gingivalis and in P.
      assaccharolytica but fine and fibrillary in preparations of Bact. salivosus and
      cat Group 2 organisms. Wet india ink preparations showed a large capsule although
      those of Bact. salivosus and Group 2 appeared largest. Five-day Group 2 broth
      cultures featured a thick ropy growth consistent with a large accumulation of
      extracellular slime. Enzymatic activities of the 24 strains measured by API ZYM
      system as well as the conventional biochemical tests showed it was possible to
      differentiate reliably Bact. salivosus from the other cat strains of
      asaccharolytic pigmented Bacteroides species and from human P. gingivalis and P.
      endodontalis by a combination of these tests. These tests suggest that Bact.
      salivosus is unlikely to belong to the genus Prevotella. Its place within the
      genus Porphyromonas is still to be determined.

PMID- 1353759
TI  - Effect of mechanical removal of pili on gliding motility of Myxococcus xanthus.
AB  - Gliding motility of Myxococcus xanthus is governed by both the adventurous (A)
      and the social (S) motility gene systems. The presence of pili has previously
      been shown to be correlated with a genetically intact S-motility system (D.
      Kaiser, Proc. Natl. Acad. Sci. USA 76:5952-5956, 1979). The purpose of the
      present work was to study the direct effect of mechanical removal of pill on the
      social motility of M. xanthus. Depiliation resulted in (i) a loss of streaming
      motility of A- S+ mutants, i.e., strains which are able to move by virtue of the
      S-motility system only, (ii) no effect on motility in A+ S- mutants, i.e.,
      strains capable of movement by the A-motility system only, and (iii) a
      retardation of streaming speed in the wild-type strain (A+ S+). Cell-cell
      cohesion, another characteristic of social behavior, was not affected by
      mechanical removal of pill. The observation that mechanical depiliation perturbed
      the motility of strains which rely on the S-motility system strongly supports a
      role for pili in social motility of M. xanthus.

PMID- 1353760
TI  - Biosynthetic thiolase from Zoogloea ramigera. Mutagenesis of the putative active
      site base Cys-378 to Ser-378 changes the partitioning of the acetyl S-enzyme
      intermediate.
AB  - The proposed active-site base Cys-378 of thiolase, responsible for deprotonation
      of acetyl-CoA, has been converted to a less acidic residue Ser-378 by
      mutagenesis. Comparison of the CD spectra and dimethyl suberimidate cross-linking
      experiments of the wild type, mutant Ser-378, and Gly-378 enzymes indicated that
      there have been no major conformational changes. The Ser-378 enzyme retains 0.1%
      of the Vmax of wild type in the direction of acetoacetyl-CoA thiolytic cleavage
      and 0.07% of the Vmax in the Claisen condensation direction. Analysis of the
      acetyl S-enzyme intermediate partitioning, that is capture of the acetyl enzyme
      by 1) the thiolate of coenzyme A relative to 2) the C-2 carbanion of acetyl-CoA,
      is changed to favor reaction 2 in the case of the Ser-378 mutant enzyme.

PMID- 1353761
TI  - Evidence for synthesis of scrapie prion proteins in the endocytic pathway.
AB  - Infectious scrapie prions are composed largely, if not entirely, of an abnormal
      isoform of the prion protein (PrP) which is designated PrPSc. A chromosomal gene
      encodes both the cellular prion protein (PrPC) as well as PrPSc. Pulse-chase
      experiments with scrapie-infected cultured cells indicate that PrPSc is formed by
      a post-translational process. PrP is translated in the endoplasmic reticulum,
      modified as it passes through the Golgi, and is transported to the cell surface.
      Release of nascent PrP from the cell surface by phosphatidylinositol-specific
      phospholipase C or hydrolysis with dispase prevented PrPSc synthesis. At 18
      degrees C, the synthesis of PrPSc was inhibited under conditions that other
      investigators report a blockage of endosomal fusion with lysosomes. Our results
      suggest that PrPSc synthesis occurs after PrP transits from the cell surface.
      Whether all of the PrP molecules have an equal likelihood to be converted into
      PrPSc or only a distinct subset is eligible for conversion remains to be
      established. Identifying the subcellular compartment(s) of PrPSc synthesis should
      be of considerable importance in defining the molecular changes that distinguish
      PrPSc from PrPC.

PMID- 1353762
TI  - Conalbumin-conjugated silica gel, a new chiral stationary phase for high
      performance liquid chromatography.
AB  - A new chiral stationary phase using conalbumin (from chicken egg white) was
      developed for high-performance liquid chromatography. Chiral resolution of
      racemic azelastine, an antiallergic drug, was achieved on a conalbumin-conjugated
      silica gel column. The effects of the pH, the concentration of organic solvents
      and salts in the mobile phase, and the temperature on the capacity factor and
      resolution of racemic azelastine were examined. This column shows good stability
      and can separate optical isomers with an aqueous mobile phase. It should be very
      useful in studies on pharmacokinetics and in clinical chemistry.

PMID- 1353763
TI  - Prazosin suppresses development of axonal damage in rats inoculated for
      experimental allergic encephalomyelitis.
AB  - The effectiveness of the alpha 1-adrenergic antagonist prazosin for preventing
      monoaminergic axonal damage in the spinal cords of rats that were inoculated for
      experimental allergic encephalomyelitis (EAE) was assessed using
      immunohistochemistry. Prazosin injections (2 mg, i.p.) given twice daily from day
      7 to day 15 postinoculation significantly reduced paralysis, spinal cord
      inflammation and monoaminergic axonal damage compared to saline injections. A
      close positive correlation between severity of inflammation and severity of
      axonal damage was found for both prazosin- and saline-treated rats that were
      inoculated for EAE. These findings confirmed previous observations of suppression
      of the development of clinical signs of EAE by prazosin treatment and supported
      the hypothesis that some factor associated with spinal cord inflammation may be
      responsible for the bulbospinal monoaminergic axonal damage that occurs during
      EAE.

PMID- 1353764
TI  - Receptor guanylyl cyclases.
AB  - Three different guanylyl cyclase cell receptors are known, but others will likely
      be discovered within the next few years. The general function of these receptors
      appear to relate to the regulation of fluid volume or fluid movement. New
      receptors, or possibly the currently known receptors, therefore, may be
      discovered in areas of the body where fluid volume regulation is important. Such
      fluids whose volume or composition might be regulated by guanylyl cyclase
      receptors include synovial fluid, uterine/oviductal luminal fluid, follicular
      fluid, aqueous humor, cerebral spinal fluid, seminiferous tubule luminal fluid,
      epididymal luminal fluid, seminal plasma, and airway luminal fluid. The function
      of the heterodimeric forms of guanylyl cyclase appear to relate to a primary
      regulation of nitric oxide (or similar molecules) concentrations, which are in
      turn regulated by a Ca2+/calmodulin-sensitive nitric oxide synthase.

PMID- 1353765
TI  - Insulin and glucocorticoid dependence of hepatic gamma-glutamylcysteine
      synthetase and glutathione synthesis in the rat. Studies in cultured hepatocytes
      and in vivo.
AB  - We reported that glucagon and phenylephrine decrease hepatocyte GSH by inhibiting
      gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH
      synthesis (Lu, S.C., J. Kuhlenkamp, C. Garcia-Ruiz, and N. Kaplowitz. 1991. J.
      Clin. Invest. 88:260-269). In contrast, we have found that insulin (In, 1
      microgram/ml) and hydrocortisone (HC, 50 nM) increased GSH of cultured
      hepatocytes up to 50-70% (earliest significant change at 6 h) with either
      methionine or cystine alone as the sole sulfur amino acid in the medium. The
      effect of In occurred independent of glucose concentration in the medium. Changes
      in steady-state cellular cysteine levels, cell volume, GSH efflux, or expression
      of gamma-glutamyl transpeptidase were excluded as possible mechanisms. Both
      hormones are known to induce cystine/glutamate transport, but this was excluded
      as the predominant mechanism since the induction in cystine uptake required a lag
      period of greater than 6 h, and the increase in cell GSH still occurred when
      cystine uptake was blocked. Assay of GSH synthesis in extracts of detergent
      treated cells revealed that In and HC increased the activity of GCS by 45-65%
      (earliest significant change at 4 h) but not GSH synthetase. In and HC treatment
      increased the Vmax of GCS by 31-43% with no change in Km. Both the hormone
      mediated increase in cell GSH and GCS activity were blocked with either
      cycloheximide or actinomycin D. Finally, when studied in vivo, streptozotocin
      treated diabetic and adrenalectomized rats exhibited lower hepatic GSH levels and
      GCS activities than respective controls. Both of these abnormalities were
      prevented with hormone replacement. Thus, both in vitro and in vivo, In and
      glucocorticoids are required for normal expression of GCS.

PMID- 1353766
TI  - Interaction between alpha 2-adrenergic and angiotensin II systems in the control
      of glomerular hemodynamics as assessed by renal micropuncture in the rat.
AB  - The hypothesis that renal alpha 2 adrenoceptors influence nephron filtration rate
      (SNGFR) via interaction with angiotensin II (AII) was tested by renal
      micropuncture. The physical determinants of SNGFR were assessed in adult male
      Munich Wistar rats 5-7 d after ipsilateral surgical renal denervation (DNX). DNX
      was performed to isolate inhibitory central and presynaptic alpha 2 adrenoceptors
      from end-organ receptors within the kidney. Two experimental protocols were
      employed: one to test whether prior AII receptor blockade with saralasin would
      alter the glomerular hemodynamic response to alpha 2 adrenoceptor stimulation
      with the selective agonist B-HT 933 under euvolemic conditions, and the other to
      test whether B-HT 933 would alter the response to exogenous AII under conditions
      of plasma volume expansion. In euvolemic rats, B-HT 933 caused SNGFR to decline
      as the result of a decrease in glomerular ultrafiltration coefficient (LpA), an
      effect that was blocked by saralasin. After plasma volume expansion, B-HT 933
      showed no primary effect on LpA but heightened the response of arterial blood
      pressure, glomerular transcapillary pressure gradient, and LpA to AII. The
      parallel results of these converse experiments suggest a complementary
      interaction between renal alpha 2-adrenergic and AII systems in the control of
      LpA.

PMID- 1353768
TI  - Round table conference on ventilatory failure, Brussels, Belgium, March 16-18,
      1991.
AB  - It was possible to reach agreement on several important issues relating to VF.
      First, the phenomenon of CO2 retention may have both pathophysiologic and
      compensatory components. There is increased awareness of the nature, intensity,
      and significance of the cross-talk between the ventilatory control center and the
      pump itself, as expressed in breathing pattern and indices of ventilatory drive.
      We are learning to interpret that information more effectively to assess
      functional reserve. Second, knowledge concerning the relative importance of
      various muscle groups is still incomplete, and the impact of disease on muscle
      function, lung mechanics, and ventilatory control is not fully understood.
      Dynamic hyperinflation and sleep disturbances provide two clear examples of
      conditions whose wide-ranging influence on drive, workload, and muscle function
      was, until quite recently, under appreciated. Finally, there was a general
      consensus that our therapeutic approaches to VF should be modified to reflect
      improved understanding of the pathogenesis of CO2 retention and iatrogenic lung
      injury. In the acute setting, measures to limit alveolar distention, such as
      controlling airway pressure, revising blood gas targets, and/or using adjunctive
      methods for blood gas exchange may avoid barotraumatic edema and rupture. The
      potential for non-invasive ventilation to avert intubation, facilitate ventilator
      withdrawal, and help patients with chronic VF to achieve compensation without
      machine dependence is now being actively investigated. This two day conference
      proved a stimulating forum for interchange of ideas regarding the state of the
      field, and allowed many opportunities for scientific interaction, both during
      outside the formal program.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353769
TI  - Do interactional capacities based on observed behaviour interfere with
      improvement in severely depressed patients? A longitudinal study.
AB  - This study examined whether the interaction of severely depressed patients and a
      psychiatrist was related to the course of depression during hospitalization.
      Interactional processes were defined on the basis of directly observed behaviour
      displayed during an interview and by the use of ethological methods. The
      behavioural structure of the interaction could be described by five factors. The
      severity of depression and the level of the behaviour factors were assessed just
      after admission (at baseline) and 10 weeks later. Patients were divided a
      posteriori into non-improved patients (N = 13) and improved patients (N = 18).
      Patients who did not improve displayed more 'speaking-effort' (looking,
      gesticulating, head movements during speech) and less 'active-listening' (head
      movements and intensive body touching during listening to the psychiatrist) than
      those who did improve. These factors increased over time in the improved patients
      but not in the non-improved patients suggesting that they may play a role in the
      maintenance of depression. The study illustrates the possible value of an
      ethological approach in the study of interactional processes.

PMID- 1353767
TI  - Both immunity and hyperresponsiveness to Pneumocystis carinii result from
      transfer of CD4+ but not CD8+ T cells into severe combined immunodeficiency mice.
AB  - The opportunistic pathogen Pneumocystis carinii (Pc) is considered to be the
      leading cause of morbidity in patients with AIDS. It is important, therefore, to
      determine the immunological mechanisms of resistance to Pc. We have taken
      advantage of the lack of both T and B lymphocytes in severe combined
      immunodeficiency (scid) mice to determine the critical factors in resistance to
      spontaneously acquired Pc pneumonia. Using adoptive transfer of unfractionated or
      fractionated lymphocyte subsets or hyperimmune serum from congenic normal donors,
      we have demonstrated that effective immunity to Pc results from the action of
      CD4+ but not CD8+ T cells (in the absence of antibody) or from humoral immunity
      (in the absence of T cells). However, responses of CD4+ T cells (but not
      antibody) to already well-established burdens of Pc are often accompanied by a
      fatal hyperinflammatory reaction. The activity of CD4+ T cells against Pc thus
      illustrates a broadly applicable principle that T cell immunity represents a
      critical balance between consequences beneficial and harmful to the host.

PMID- 1353770
TI  - Dermatofibrosarcoma protuberans: 4 years after local trauma.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a low grade, fibrohistiocytic malignant
      soft tissue tumor that arises infrequently in the foot and ankle region. It most
      frequently demonstrates a "storiform" histologic pattern, and if incompletely
      excised, may be recurrent, more anaplastic and metastatic. Soft tissue plain film
      radiography, as well as magnetic resonance imaging (MRI) help outline the tumor
      and involved tissues, which is beneficial in staging, determining surgical
      approach and evaluation of therapy. Definitive diagnosis is made by biopsy. A
      dermatofibrosarcoma protuberans is reported in the foot of a 14-year-old female
      patient, 4 years after trauma to the site.

PMID- 1353771
TI  - Pregnancy and Takayasu's aorto-arteritis.

PMID- 1353773
TI  - Radical effects on mutation spectra in lambda phage.
AB  - Mutations in the lambda repressor gene cI (710 bp) were induced by 60Co-gamma
      radiation in dissolved lambda phage DNA. After in vitro DNA packaging to lambda
      phage particles (pack phage) and phenotypic expression of the mutants, DNA was
      sequenced directly. Two-thirds of mutations were located in the amino terminus
      region of the gene without any signs of hotspots. Changes consisted of (+1)
      insertions (25%) and base substitutions (75%). Transitions were exclusively G/C
      to A/T. Transversions were mostly G/C to C/G and few G/C to T/A. We did not find
      A/T to T/A transversions, A/T to G/C transitions, deletions and gross
      rearrangements. In most of the base substitutions a pre-existing base pair had
      been replaced by an A/T pair; this might come from 'non-instructional sites' like
      abasic sites. Several mechanisms for base substitutions are considered.

PMID- 1353772
TI  - Repair of ionizing radiation damage in primate alpha DNA transfected into rat
      cells.
AB  - The time-course of repair of irradiated primate alpha DNA was studied after
      transfection and recovery from rat NRK cells. Rat cells were chosen for
      transfection because they have no alpha DNA. Plasmid pBUC4 alpha 10, containing
      10 tandem 172 bp alpha DNA subunits in its 5 kbp DNA, was irradiated and
      introduced into the rat cells by electroporation. The transfected alpha DNA was
      then recovered from NRK nuclei free of extraneous rat DNA, permitting study of
      the fate of the transfected alpha DNA in time-course experiments. alpha DNA
      continuously entered nuclei for processing in the first 2.5 h after transfection.
      The pool of damaged bases in alpha DNA in NRK nuclei was detectable 2.5 h after
      transfection. Radiation-induced alpha DNA fragments of electrophoretic mobility
      intermediate between those of unit nucleotide length were prominent in sequencing
      gel analyses of alpha DNA for 5-150 min after transfection. These intermediate
      mobility fragments initially disappeared with T 1/2 of 6-20 min. The alpha DNAs
      of intermediate mobility are presumed to be intermediates in DNA repair. Residual
      DNA base damage which had not been processed in the transfected cells could later
      be unmasked in vitro by conversion to strand breaks by beta-elimination using
      heat and piperidine or endonuclease III of E. coli. Irradiation of the recipient
      NRK cells with 5 Gy 4 hours before transfection prolonged the time during which
      intermediate mobility species could be found, consistent with the increased
      frequency of intermediate mobility species observed in DNA of monkey CV-1 cells
      pretreated with small doses of radiation before 300 Gy (Bases et al. 1990).

PMID- 1353774
TI  - Detection of single-strand breaks and base damage in DNA of blood cells from
      leukaemia patients receiving chemo- and radiotherapy.
AB  - Chemotherapy combined with total-body irradiation (TBI), a conditioning regimen
      for bone-marrow transplantation (BMT), causes lesions in the cellular DNA of the
      patients treated. To understand possible consequences of the DNA damage induced
      during such treatment, information is required about the nature of the damage,
      the level of induction and its persistence, and about the importance of the
      various lesions for cell-lethality and/or mutation induction. Recently, we
      developed a sensitive immunochemical method to quantify single-strand breaks
      (SSB) in the DNA of mammalian cells. In addition, a modification of the so-called
      alkaline elution technique was introduced which allows quantification of SSB
      together with base damage (SSB+BD). These methods have now been applied
      successfully to study the in vivo induction and repair of DNA damage in WBC of
      leukaemia patients who prior to BMT were treated with cyclophosphamide (CY) and
      received TBI. SSB and SSB+BD were determined after two treatments with CY (60 mg
      kg-1) followed by TBI (4.5-8.6Gy). The CY treatments gave rise to rather
      persistent SSB. In addition to these, radiation-induced SSB and SSB+BD could be
      detected shortly after TBI. However, 105 min after TBI, these SSB could be
      observed no longer, as a result of rapid repair.

PMID- 1353775
TI  - Oncogenes in X-ray-transformed C3H 10T1/2 mouse cells and in X-ray-induced mouse
      fibrosarcoma (RIF-1) cells.
AB  - In order to better understand the molecular basis of X-ray induced carcinogenesis
      we have investigated RNA levels of oncogenes in an X-ray transformed C3H 10T1/2
      fibroblast line (XTD) and RIF-1 cells isolated from an X-ray-induced fibrosarcoma
      in a C3H mouse. Steady-state levels of K-ras, H-ras, N-ras, abl, sis, src, and
      fos were unchanged in the X-ray-transformed cells compared with non-transformed
      C3H 10T1/2 cells. However, myc and raf mRNA levels were increased dramatically in
      the transformed cells. Data further suggests a possible alteration in processing
      of raf RNA in the XTD cells. Southern blot analysis of secondary transfectants
      induced with XTD DNA indicated that the oncogenic phenotype did not segregate
      with the myc or raf loci; nor with nine other oncogenes analysed.

PMID- 1353776
TI  - Rapid translocation frequency analysis in humans decades after exposure to
      ionizing radiation.
AB  - This paper presents an analysis of the utility of fluorescence in situ
      hybridization (FISH) with whole-chromosome probes for measurement of the genomic
      frequency of translocations found in the peripheral blood of individuals exposed
      to ionizing radiation. First, we derive the equation: Fp = 2.05fp(1-fp)FG,
      relating the translocation frequency, Fp, measured using FISH to the genomic
      translocation frequency, FG, where fp is the fraction of the genome covered by
      the composite probe. We demonstrate the validity of this equation by showing
      that: (a) translocation detection efficiency predicted by the equation is
      consistent with experimental data as fp is changed; (b) translocation frequency
      dose-response curves measured in vitro using FISH agree well with dicentric
      frequency dose-response curves measured in vitro using conventional cytogenetic
      procedures; and (c) the genomic translocation frequencies estimated from FISH
      measurements for 20 Hiroshima A-bomb survivors and four workers exposed to
      ionizing radiation during the Y-12 criticality accident are approximately the
      same as the translocation frequencies measured using G-banding. We also show that
      translocation frequency dose response curves estimated using FISH are similar for
      Hiroshima A-bomb survivors and for first division lymphocytes irradiated in
      vitro. We conclude with a discussion of the potential utility of translocation
      frequency analysis for assessment of the level of acute radiation exposure
      independent of the time between analysis and exposure.

PMID- 1353777
TI  - Radioprotection mediated by the haemopoietic stimulation conferred by AM5: a
      protein-associated polysaccharide.
AB  - The haemopoietic and radioprotective effects of a protein-associated
      polysaccharide named AM5, have been studied following i.v. injection in mice. A
      dose-related accumulation of the splenic granulocyte-macrophage colony-forming
      units (CFU-GM) and colony-forming units in the spleen (CFU-S) was observed in
      mice treated with doses ranging from 0.1 to 0.4 mg/kg of AM5. The accumulation of
      splenic CFU-S, CFU-GM and BFU-e (erythroid burst-forming units) was always
      maximal 5 days after treatment with 0.4 mg/kg of AM5, with increases over control
      values between 300% and 500%. When the number of haemopoietic progenitors was
      quantified in the bone marrow, only slight increases of CFU-S were obtained,
      corresponding to the administration of low doses of AM5 (0.1 mg/kg). However,
      significant increases of circulating CFU-S were observed following administration
      of higher doses of AM5, suggesting a mobilization of haemopoietic progenitors
      from this organ. A faster recovery of spleen CFU-GM was observed in mice treated
      with 0.4 mg/kg of AM5 3 days or 1 day prior to a sublethal irradiation, and at
      this later time AM5 produced a significant survival enhancement from 10% to 90%
      in mice irradiated with 7.6 Gy X-rays. This effect was correlated with an
      increase in the nadir of leucocytes, characteristic of the radiation syndrome.

PMID- 1353778
TI  - Radioreductive effect of bestatin (Ubenimex) in BALB/c mice.
AB  - The radioreductive effect of Bestatin (Ubenimex), a biological response modifier,
      was examined in BALB/c mice. Consecutive daily administrations from day 0 to day
      3 after lethal irradiation resulted in a dose reduction factor (DRF) of 1.03. In
      haematological studies Bestatin enhanced the recovery of peripheral leucocytes in
      sublethally irradiated mice by activating colony-stimulating factors (CSF) in
      serum, leading to enhanced recovery of GM-CFC. There was no enhancement of CSF in
      BALB/c nude mice. On the other hand, Bestatin showed no effect on day 12 CFU-S
      and day 7 CFU-S after the sublethal irradiation, though there was a trend that
      the drug stimulated numbers of day 7 CFU-S after irradiation. These results
      strongly suggest that Bestatin enhanced the CSF activity by modulating T cell
      function, resulting in the augmentation of peripheral leucocytes and prolongation
      of survival of irradiated mice. This drug now used in the clinic proved to be
      modestly effective.

PMID- 1353779
TI  - Cytotoxicity, uptake and dissolution of 241AmO2 particles in dog alveolar
      macrophages in vitro.
AB  - Because alveolar macrophages play a role in the pulmonary clearance of inhaled
      particles, experiments were conducted to investigate the toxicity of 241AmO2
      particles to alveolar macrophages and the role of these macrophages in the
      dissolution of 241AmO2 particles. Beagle dog pulmonary alveolar macrophages
      obtained by bronchopulmonary lavage were exposed in vitro to selected
      concentrations of 241AmO2. Macrophage viability determined by trypan-blue dye
      exclusion technique and the ability of the alveolar macrophages to phagocytose
      opsonized sheep red blood cells were the measures of 241AmO2 toxicity. The uptake
      of 241AmO2 particles was studied as a function of time. In addition, the
      dissolution of 241AmO2 by macrophages was determined for periods up to 72 h.
      After 20 h exposure to concentrations of 241Am higher than 4.63 kBq/ml, the
      phagocytic ability of macrophages was reduced, whereas no significant change in
      cell viability was observed at this concentration. Significant cell killing
      occurred at concentrations higher than 18.5 kBq/ml. After 72 h in the cultures,
      10% of the 241AmO2 was dissolved by the alveolar macrophages. These findings
      imply that the inhalation of radioactive particles such as 241AmO2 particles
      might cause a reduction in the alveolar macrophage population in the lungs. In
      addition, the dissolution of 241AmO2 particles by alveolar macrophages might play
      a role in the short-term pulmonary clearance of inhaled 241AmO2 particles in the
      beagle dog.

PMID- 1353780
TI  - An interspecies comparison of the phagocytosis and dissolution of 241AmO2
      particles by rat, dog and monkey alveolar macrophages in vitro.
AB  - Because of the role that alveolar macrophages (PAM) play in the pulmonary
      clearance of inhaled particles via mechanical transport and dissolution,
      understanding the uptake and dissolution of particles by these cells might
      provide insight into the mechanisms of particle dissolution in lungs of various
      species and hence facilitate the extrapolation of animal data to humans.
      Therefore, experiments were conducted to study the phagocytosis and dissolution
      of 241AmO2 particles by rat, dog and monkey PAM in vitro. Rat, dog and monkey PAM
      were exposed for up to 72 h to 0.19, 0.93 or 4.6 kBq/ml 241Am, after which cell
      viability was determined. The 241Am concentration, 4.63 kBq/ml, was used for the
      phagocytosis and dissolution experiments. The phagocytosis and dissolution of
      241AmO2 particles were followed up to 20 and 72 h, respectively. Dog and monkey
      PAM took up 241AmO2 particles at similar rates, whereas rat PAM phagocytosed only
      60% of the amount phagocytosed by dog and monkey PAM at 20 h. The PAM of the
      three species dissolved 241AmO2 particles at similar rates; 8-10% was dissolved
      by 72 h. The results of the 241AmO2 uptake in vitro may reflect in vivo
      situations, where the differences in uptake seen in vitro would probably diminish
      at later times after exposure. The dissolution results imply that the dissolution
      of 241AmO2 particles by alveolar macrophages of the three species might be
      species-independent. This, at least, might be true for dog and monkey, where in
      vivo data have shown that 241AmO2 was translocated similarly in both species.
      Finally, the alveolar macrophage culture system provides a useful simulation to
      investigate uptake and dissolution of inhaled particles.

PMID- 1353781
TI  - Model of DNA damage induced by radiations of various qualities.
AB  - A theoretical model permitting estimation of yields of various DNA damages
      induced by radiations of varying qualities is described. It is based on the Monte
      Carlo track structure simulation and DNA structure, and links physical,
      physicochemical and chemical stages of radiation action. Direct and indirect
      effects are not strictly distinguished but treated cooperatively. Good agreement
      between calculated and measured initial yields of double-strand breaks was
      observed. Other multiple and single damages of DNA are studied. When radiation
      quality is changed there are quantitative and qualitative transitions in the
      damage spectrum. The proportion of multiple damage in the damage spectrum is
      about 30% for low-LET radiations and increases considerably with increasing
      ionization density.

PMID- 1353782
TI  - Incidence of brain tumours in rats exposed to an aerosol of 239PuO2.
AB  - Incidence of brain tumours was investigated in 3390 female and male Wistar rats
      exposed to an aerosol of 239PuO2, or as sham-exposed controls. Lung doses ranged
      from 0.05 to 22 Gy. In females, six brain tumours were found in 1058 control rats
      (incidence, 0.6%) and 24 brain tumours in 2134 rats exposed to Pu (incidence,
      1.1%); the survival-adjusted level of significance was p = 0.29 for comparing
      control with exposed females. In males, two brain tumours were found in 60
      control rats (incidence, 3.3%) and seven brain tumours in 138 rats exposed to Pu
      (incidence, 5.1%); the survival-adjusted level of significance was p = 0.33.
      Brain tumour incidence was about five times greater in male than in female rats
      (p = 0.0001), demonstrating a highly significant sex difference in brain tumour
      incidence. Tumour types were distributed similarly among control and Pu-exposed
      groups of both sexes; most tumours were astrocytomas. Mean lifespans for rats
      with brain tumours were not significantly different between control and Pu
      exposed rats. Plutonium was not detected on autoradiograms of the brain. These
      results, like those for plutonium workers, show an increase of brain tumours
      which cannot be demonstrated statistically to be related to radiation exposure.

PMID- 1353783
TI  - Monoamines and neuropeptides as transmitters in the sedentary polychaete
      Sabellastarte magnifica: actions on the longitudinal muscle of the body wall.
AB  - Pharmacological studies on the body wall musculature of the sedentary polychaete
      Sabellastarte magnifica show a potential neurotransmitter role for monoamines and
      neuropeptides in this organism. All catecholamines induced contraction of
      longitudinal muscle strips, while serotonin and the neuropeptides FMRFamide and
      substance P caused a relaxation of both resting and active muscle. In addition,
      we demonstrate catecholaminergic and serotonergic pathways in the nervous system
      of this sabellid, using immunohistochemistry and catecholamine-induced
      fluorescence. The presence of neuropeptide-containing fibers in the nervous
      system of this polychaete has been previously reported. Together these results
      suggest that catecholamines act as excitatory transmitters on the longitudinal
      muscle cells of the body wall of S. magnifica, while serotonin and FMRFamide, and
      possible substance P, are inhibitory transmitters. The possibility of coexistence
      of serotonin and FMRFamide within the same neuronal cell bodies and fibers of
      this polychaete is also explored.

PMID- 1353784
TI  - Isolation and characterization of a ntrC mutant of Bradyrhizobium (Parasponia)
      sp. ANU289.
AB  - A mutant of Bradyrhizobium (Parasponia) sp. ANU289 affected in the regulation of
      nitrogen metabolism was isolated. The mutant, designated ANU293, was unable to
      induce ammonium transport (Amt), nitrate reductase (NR) or glutamine synthetase
      II (GSII) activities under conditions that induce these activities in the wild
      type. However, glutamine synthetase I (GSI), which is expressed constitutively in
      the wild-type, was present at normal levels in the mutant. The mutant also
      retained the ability to fix nitrogen in vitro and in planta, although nodule
      development on siratro (Macroptilium atropurpureum) was retarded. Southern blot
      analysis showed that ntrC, the product of which is involved in regulation of
      nitrogen metabolism, is the site of pSUP1021 insertion in ANU293. These results
      indicate that the transcriptional activator NtrC is required for the expression
      of Amt, NR and GSII, but not GSI or nitrogenase in Bradyrhizobium (Parasponia)
      sp. ANU289.

PMID- 1353785
TI  - Evaluation of a ribosomal RNA gene probe for the identification of species and
      subspecies within the genus Staphylococcus.
AB  - To evaluate a 16S rRNA gene probe for the identification of staphylococcal
      species and subspecies, we have augmented previous studies involving 12
      staphylococcal species by analysing the remaining 16 species currently classified
      in the genus Staphylococcus. HindIII- and EcoRI-restricted DNA of isolates from
      validly described species of Staphylococcus was probed with radiolabelled plasmid
      pBA2 containing 16S rDNA from Bacillus subtilis. The Dice coefficient was used to
      assess similarity between the 74 HindIII- and the 81 EcoRI-hybridization patterns
      obtained from a total of 271 isolates belonging to 31 staphylococcal taxa (28
      species, of which three include two subspecies). The use of HindIII yielded a
      better discrimination of the staphylococci than the use of EcoRI. All of the
      isolates belonging to the same species or subspecies, except S. hyicus isolates,
      were recovered as homogeneous clusters using their HindIII hybridization
      patterns. The phenotypically close taxa were clearly distinguished. Thus, the
      method presented in this study constitutes a powerful tool for the identification
      of taxa within the genus Staphylococcus.

PMID- 1353786
TI  - The molecular analysis of synonymy among medically important yeasts within the
      genus Candida.
AB  - Three sets of medically important yeasts, Candida albicans, C. tropicalis, and C.
      krusei, were compared with their putative synonyms (C. langeronii and C.
      claussenii, C. paratropicalis, and Itssatchenkia orientalis, respectively) to
      determine if these synonyms are genetically distinguishable from each other.
      Pulsed-field electrophoresis and hybridization to species-specific probes were
      used to accomplish this goal. The species-specific probes for C. albicans and C.
      tropicalis have been previously described (27A and CT13.8, respectively) whereas
      the probe for C. krusei (CK3) was cloned in this study. No distinguishing
      characteristics between synonyms were identified, thus supporting the current
      taxonomic treatment of these organisms.

PMID- 1353787
TI  - Effect of pH on glutamine content derived from exogenous glutamate in astrocytes.
AB  - A shift in pH from 7.4 to 7.8 in the incubation solution caused a 3.4-fold
      increase in the free glutamine content of mouse cerebral astrocytes that were
      incubated with glutamate (100 microM) and ammonium (100 microM). This large and
      reversible steady-state increase in glutamine content was accompanied by smaller
      transient increases in the following: (a) net formation of glutamine; (b)
      clearance of glutamate from the incubation solution; and (c) glutamate content.
      The content of glutamine was reduced markedly by omission of either glutamate or
      ammonium from the incubation solution, or by inhibition of glutamine synthetase
      activity with methionine sulfoximine. The rate at which glutamine was exported
      from the astrocytes was unaffected by the pH change. The effects of pH on the
      concentration of free ammonia or on glutamate uptake do not appear to mediate the
      increase in glutamine content. Uptake of exogenous glutamine was little affected
      by the pH change. Therefore, possible mediation of the effect by an increase in
      intracellular pH must be considered. The response to altered pH described here
      may provide a cellular basis for the increased level of brain glutamine observed
      in hyperammonemia.

PMID- 1353788
TI  - Distribution of protein phosphatase inhibitor-1 in brain and peripheral tissues
      of various species: comparison with DARPP-32.
AB  - The distribution of inhibitor-1, a cyclic AMP-regulated inhibitor of protein
      phosphatase-1, was analyzed in various brain regions and peripheral tissues of
      various species by immunolabeling of sodium dodecyl sulfate-poly-acrylamide gel
      transfers using specific antibodies. The distribution of inhibitor-1 was directly
      compared to that of DARPP-32, a structurally related cyclic AMP-regulated
      inhibitor of protein phosphatase-1. In rat CNS, a single immunoreactive protein
      of M(r) 30,000, identified as inhibitor-1, was widely distributed. In contrast,
      DARPP-32 was highly concentrated in the basal ganglia. Inhibitor-1 was detected
      in brain tissue from frog (M(r) 27,000), turtle (M(r) 29,000/33,000), canary
      (M(r) 26,000), pigeon (M(r) 28,000), mouse (M(r) 30,500), rabbit (M(r) 26,500),
      cow (M(r) 27,000), and monkey (M(r) 27,500), but not from goldfish. Inhibitor-1
      was detected at various levels in most peripheral tissues of the species studied;
      however, it was not detectable in certain tissues of particular species (e.g.,
      rat and cow liver). DARPP-32 was detected in brain tissue of all the species
      tested except frog and goldfish, but was not detectable in most peripheral
      tissues. Both inhibitor-1 and DARPP-32 were concentrated in the cytosol and
      synaptosomal cytosol of rat striatum. The developmental expressions of inhibitor
      1 and DARPP-32 in rat striatum differed: the level of inhibitor-1 peaked in the
      first postnatal week and then declined by the third postnatal week, whereas the
      level of DARPP-32 increased to a peak level by the third postnatal week and
      remained elevated thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353789
TI  - Striatal protection induced by lesioning the substantia nigra of rats subjected
      to focal ischemia.
AB  - Unilateral 6-hydroxydopamine lesion of the substantia nigra reduced the volume of
      striatal necrosis and suppressed the increase in extracellular glutamate
      concentration in the striatum induced by middle cerebral artery occlusion in
      rats. These results indicate that the dopaminergic nigrostriatal pathway is
      highly involved in the vulnerability of the striatum to ischemia and suggest that
      glutamate-dopamine interactions may play a key role in the striatal ischemic
      insult.

PMID- 1353791
TI  - Activation by nitric oxide of guanylate cyclase in endothelial cells from brain
      capillaries.
AB  - Endothelial cells (ECs) from brain microvessels respond to exogenous nitric oxide
      (NO) donor molecules (N-ethoxycarbonyl-3-morpholinosydnonimine and sodium
      nitroprusside) with large (greater than 15-fold) increases in cyclic GMP (cGMP)
      levels. Comparable actions of sodium nitroprusside were observed in vascular
      smooth muscle cells and in neuroblastoma cells. Coculturing brain capillary ECs
      in the presence of N1E-115 neuroblastoma cells increased their cGMP levels
      fourfold. A further increase was observed in the presence of 50 nM neurotensin,
      although brain capillary ECs lack receptor sites for neurotensin. The
      neuroblastoma cell-dependent formation of cGMP was suppressed by 0.1 mM L-NG
      monomethylarginine, indicating that NO, produced by N1E-115 cells in response to
      neurotensin, activated guanylate cyclase in brain capillary ECs. Similarly,
      culturing brain capillary ECs in the presence of aortic ECs increased their cGMP
      content in a manner that was amplified by bradykinin and that was inhibited by L
      NG-monomethylarginine. Bradykinin had no action in pure cultures of brain
      capillary ECs. It is concluded that brain capillary ECs express high levels of
      guanylate cyclase activity that could be activated by exogenous NO donor
      molecules and by NO produced by neuroblastoma cells and by aortic ECs in response
      to specific agonists. Brain capillary ECs are thus potential target cells for
      brain-derived NO.

PMID- 1353790
TI  - Glutamate inhibits adenylate cyclase activity in dispersed rat hippocampal cells
      directly via an N-methyl-D-aspartate-like metabotropic receptor.
AB  - Three major subtypes of glutamate receptors that are coupled to cation channels-
      N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methylisoxazole
      4-propionate (AMPA) receptors--are known as ionotropic receptors in the mammalian
      CNS. Recently, an additional subtype that is coupled to GTP binding proteins and
      stimulates (or inhibits) metabolism of phosphoinositides has been proposed as a
      metabotropic receptor. Incubation of dispersed hippocampal cells from adult rats
      with glutamate or NMDA decreased forskolin-stimulated cyclic AMP (cAMP)
      accumulation; half-maximal effects were obtained with 5.6 +/- 2.2 and 6.4 +/- 2.3
      microM, respectively. Kainate and quisqualate were less potent. The effect of
      glutamate was antagonized by 2,3-diaminopropionate and 2-amino-5
      phosphonovalerate, NMDA/glutamate receptor antagonists, but not by 0.5 microM
      Joro spider toxin, a specific blocker of the AMPA receptor. The inhibitory effect
      of glutamate on cAMP formation was not blocked by 2 microM tetrodotoxin or by the
      absence of Ca2+. In hippocampal membranes, glutamate, similar to carbachol,
      inhibited adenylate cyclase activity in a GTP-dependent manner. These findings
      suggest that the glutamate inhibition of adenylate cyclase is direct and is not
      due to a result of the release of other neurotransmitters. The effect of
      glutamate on cAMP accumulation was observed in an assay medium containing 0.7 mM
      MgCl2, which is known to inhibit both ionotropic NMDA receptor/channels in the
      hippocampus and metabotropic NMDA receptors in the cerebellum. The inhibitory
      effect of glutamate was abolished by pertussis toxin treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1353792
TI  - Regulatory interactions among axon terminals affecting the release of different
      transmitters from rat striatal slices under hypoxic and hypoglycemic conditions.
AB  - An in vitro model of ischemia was utilized to study the effects of both oxygen
      and glucose depletion on transmitter release from rat striatal slices. The
      spontaneous and stimulation-evoked releases of tritiated dopamine, gamma
      aminobutyric acid, glutamate, and acetylcholine were measured. Hypoxia increased
      the evoked release of glutamate and dopamine without effect on the resting
      release. In contrast, hypoglycemia itself increased the resting release of
      dopamine. Hypoxia in combination with hypoglycemia provoked a massive release of
      glutamate, dopamine, and gamma-aminobutyric acid. The effect on acetylcholine
      release was less pronounced. Ca2+ withdrawal partly reduced the effect of hypoxia
      combined with hypoglycemia on dopamine release and application of tetrodotoxin (1
      microM) abolished it. MK-801 (3 microM), an N-methyl-D-aspartate receptor
      antagonist, attenuated the effect of hypoxia and hypoglycemia on [3H]dopamine
      release. omega-Conotoxin (0.1 microM) had a similar effect on stimulation-evoked
      release under a hypoxic condition. The D2 receptor antagonist sulpiride (100
      microM) failed to enhance the release of [3H]acetylcholine in hypoxia combined
      with hypoglycemia. It was suggested that in response to hypoxia combined with
      hypoglycemia there is a massive release of glutamate due to the increased firing
      rate which in turn releases dopamine from the axon terminals through stimulation
      of presynaptic N-methyl-D-aspartate receptors. Dopaminergic inhibitory control on
      ACh release seems not to be operative under conditions of hypoxia combined with
      hypoglycemia.

PMID- 1353793
TI  - The role of NMDA and non-NMDA excitatory amino acid receptors in the excitation
      of primate spinothalamic tract neurons by mechanical, chemical, thermal, and
      electrical stimuli.
AB  - The role of excitatory amino acids (EAAs) in the excitation of monkey
      spinothalamic tract (STT) neurons following activation of cutaneous primary
      afferent fibers by noxious and non-noxious stimuli was investigated. The
      responses of STT neurons to either NMDA or non-NMDA EAA ligands were blocked by
      infusion of specific antagonists through a microdialysis fiber into the region
      surrounding the cells. Our results show that blockade of non-NMDA receptors
      results in a nearly complete elimination of the responses of STT neurons to all
      stimuli. Blockade of NMDA receptors results in an attenuation of the responses to
      noxious stimuli but, in addition, prevents the development of the sensitization
      of STT neurons that is often observed after intradermal injection of capsaicin.
      These observations further support a role of EAAs in the transmission of sensory
      information from primary afferent fibers to dorsal horn neurons and a role for
      NMDA receptors in the generation of hyperalgesia.

PMID- 1353795
TI  - Proceedings of the 19th Symposium on Pharmacological Activity and Mechanism.
      Kyoto, November 21-22, 1991. Abstracts.

PMID- 1353794
TI  - Long-term and short-term electrophysiological effects of estrogen on the synaptic
      properties of hippocampal CA1 neurons.
AB  - The ovarian steroids exert both long-term and short-term actions on neurons
      involving different cellular mechanisms. We have investigated the long-term and
      short-term effects of estrogen on the electrophysiological properties of CA1
      neurons utilizing intracellular recordings in hippocampal slices prepared from
      ovariectomized female rats. An in vivo estrogen-priming paradigm was used to
      examine long-term genomic actions of estrogen. Subcutaneous estrogen injections 2
      d prior to recording had no effect on the intrinsic membrane properties of CA1
      neurons, but increased synaptic excitability by prolonging the EPSP and inducing
      repetitive firing in response to Schaffer collateral stimulation. Short-term
      effects of estrogen that presumedly involve direct membrane interactions were
      tested by application of steroids directly to the slice. Superfusion of 17 beta
      estradiol, but not 17 alpha-estradiol, caused a rapid and reversible increase in
      the amplitude of the Schaffer collateral-activated EPSP. This potentiation of the
      EPSP by 17 beta-estradiol still occurred in the presence of the NMDA antagonist 2
      amino-5-phosphonovalerate, but was blocked by the non-NMDA antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione. Depolarizing responses to iontophoretic pulses of
      exogenous glutamate were also potentiated by 17 beta-estradiol, suggesting a post
      synaptic site of action. In addition, 17 beta-estradiol potentiated the responses
      to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, kainate, and
      quisqualate, but not NMDA, further implicating non-NMDA receptors in the short
      term action of estrogen. In contrast, 17 beta-estradiol had no effect on
      responses to exogenous GABA or on the Schaffer collateral-induced late
      IPSP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353796
TI  - Synthesis and antihistaminic activity of some thiazolidin-4-ones.
AB  - A new series of 2-(4- and 3-substituted phenyl)-3-[3-(N,N-dimethylamino) propyl]
      1,3-thiazolidin-4-ones were synthesized, characterized, and evaluated for their
      ability to inhibit the contractions induced by histamine on guinea pig ileum. The
      measurement of pA2 values suggested that the reported compounds showed H1
      antagonism. The more active compounds 5, 9, and 13 exhibited activity close to
      that of mepyramine.

PMID- 1353797
TI  - Spatial and temporal distribution of resting female mosquitoes (Diptera:
      Culicidae) in the coastal plain of North Carolina.
AB  - The spatial and temporal distribution of 28 species of female mosquitoes resting
      in natural (swamp, woods, and swamp-woods ecotone) and human-made (beneath
      bridges) habitats in blackwater stream-associated ecosystems in Duplin County,
      N.C., was determined by sampling with a D-Vac vacuum aspirator during 1984 and
      1985. Two types of resting distributions were evident. In type one, species
      including Aedes atlanticus Dyar & Knab, Ae. canadensis (Theobald), Ae.
      triseriatus (Say), and Psorophora ferox (von Humboldt) rested predominantly on
      vegetation and were not collected beneath bridges. In type two, species including
      Anopheles punctipennis (Say), Culex erraticus (Dyar & Knab), Cx. peccator Dyar &
      Knab, Cx. pipiens L. and Cx. quinquefasciatus Say and their hybrids, Cx. restuans
      Theobald, Cx. territans Walker, and Uranotaenia sapphirina (Osten Sacken) rested
      on vegetation, in natural shelters in swamp habitats, and beneath bridges.
      Differences in the proportion of gravid mosquitoes among habitats were evident
      for Ae. canadensis, An. punctipennis, Cx. pipiens and Cx. quinquefasciatus and
      their hybrids, Cx. restuans, Cx. territans, Ps. ferox, and Ur. sapphirina,
      indicating that gonotrophic condition may influence resting site selection.

PMID- 1353798
TI  - Statistical appraisal of the weight-wing length relationship of mosquitoes.
AB  - The relationship between wing length and body weight of mosquitoes was examined
      by comparing the fit of regressions using logarithmic and cubic transformations.
      A two-parameter line using a double logarithmic transformation provided the best
      fit, and we found no evidence to justify the use of wing length cubed as a
      transformation. Wing length was not directly proportional to body weight, but
      rather increased at a lesser rate than did body weight. Equations that predict
      body weight from wing length may not be an appropriate substitute for weighing
      mosquitoes, when studying the extremes of size in populations.

PMID- 1353799
TI  - Let's all support the Hospice Six.

PMID- 1353800
TI  - [Somatostatin analogues: a therapeutic tool in proliferative diabetic
      retinopathy?].

PMID- 1353801
TI  - Aortic valve replacement for Takayasu's arteritis.
AB  - We report 12 cases of aortic valve replacement performed for Takayasu's arteritis
      and discuss the genesis of aortic regurgitation and the clinical outcome after
      aortic valve replacement. This group of twelve patients who underwent aortic
      valve replacement between April 1982 and March 1990 included four male and eight
      female patients, aged 24 to 67 years (mean age 48 years). Preoperative
      angiography showed systemic multiple stenoocclusive or aneurysmal dilated
      vascular lesions in addition to aortic regurgitation. The multiple lesions
      included a lesion in the aortic arch branch in nine (75%), in the pulmonary
      artery in seven (58%), an aneurysmal dilation in the ascending aorta of more than
      6 cm in four (33%), a coronary lesion in four (33%), a thoracic aortic lesion in
      six (50%), and a lesion in the abdominal aorta and its visceral branch in six
      (50%). Simple aortic valve replacement alone was performed in two patients and in
      combination with another operation in ten patients, with aortic root
      reconstruction in two, ascending aortic plication in three, coronary artery
      bypass grafting in two, aortic arch branch bypass grafting in one, aortic arch
      branch bypass grafting and coronary ostium endarterectomy in one, and mitral
      valve replacement and ascending aortic plication in one. There was no operative
      death, and only one patient died later, 18 months after the operation, because of
      secondary amyloidosis. The postoperative recovery of the clinical status and
      cardiac function was good. Intraoperative observations suggested that aortic
      valve regurgitation may be caused by an extension of aortitis, although
      histopathologic examinations of the valve showed nonspecific findings. One of the
      characteristic problems in Takayasu's arteritis is the necessity for prednisolone
      administration in some patients preoperatively or postoperatively, or both. We
      conclude that aortic valve replacement for patients with Takayasu's arteritis is
      an effective and safe treatment. Our data related to the genesis of aortic
      regurgitation in Takayasu's arteritis remain insufficient to draw conclusions,
      and further analysis is planned.

PMID- 1353802
TI  - Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in
      non-insulin-dependent diabetes mellitus.
AB  - Raised urinary albumin excretion (UAE) is associated with an increased risk of
      cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM). We
      have examined the role of endothelial dysfunction as a possible explanation for
      this association in 94 NIDDM patients by investigating UAE, new cardiovascular
      events, and plasma concentration of von Willebrand factor (vWF), an indicator of
      endothelial dysfunction. At baseline, 66 patients had normal UAE (less than 15
      micrograms/min), which remained normal in 33 (group 1) and increased in 33 (to
      median 31.5 micrograms/min, group 2). In 28 patients, baseline UAE was abnormal
      (67.1 micrograms/min, group 3). Follow-up ranged between 9 and 53 months. vWF did
      not change in group 1 (median 128% at baseline and 123% at follow-up), but
      increased in group 2 (from 116 to 219%, p less than 0.0001) and group 3 (from 157
      to 207%, p = 0.0005). Baseline level of and change in vWF were strongly related
      to the development of microalbuminuria (R2 = 0.60, p less than 0.0001), but
      cardiovascular risk factors were not (R2 = 0.14). Raised baseline UAE was
      associated with an increased risk of new cardiovascular events only in patients
      with vWF concentrations above the median (relative risk 3.66, 95% CI 1.3-11.9)
      and not in patients with lower vWF (0.19, 0.01-1.33). In addition, the
      cardiovascular risk associated with increased UAE was modified by low compared
      with high concentrations of serum high density lipoprotein cholesterol (2.86
      [1.03-8.48] vs 0.15 [0.01-1.43]). Dysfunction of vascular endothelium may be a
      link between albuminuria and atherosclerotic cardiovascular disease in NIDDM.

PMID- 1353803
TI  - Randomised controlled trial of nasal nicotine spray in smoking cessation.
AB  - Studies with nicotine chewing gum and nicotine skin patches indicate that
      nicotine replacement can help people to give up smoking. The rapidity with which
      nicotine is absorbed when given as a nasal spray suggests that it might be
      effective for those for whom the other means of replacement are too slow. The
      efficacy and safety of a nasal nicotine spray as an adjunct to group treatment
      for stopping smoking were assessed in a randomised, double-blind, placebo
      controlled trial in which 227 cigarette smokers attending the Maudsley Hospital
      Smokers Clinic received 4 weeks of supportive group treatment plus active
      nicotine (0.5 mg per shot) or placebo nasal spray. The main end-point was
      biochemically validated complete abstinence from smoking from the third week of
      group treatment until the 12-month follow-up. Side-effects were assessed by self
      reports and, where necessary, by physical examination. Of subjects assigned to
      active treatment 26% (n = 30) were validated abstinent throughout the year,
      compared with 10% (n = 11) of those assigned to placebo (relative abstinence rate
      2.6, 95% CI 1.5-4.5, p less than 0.001). The advantage of the active spray was
      greatest in the heaviest smokers. Plasma nicotine concentrations from the spray
      were typically between one-half and three-quarters of baseline smoking levels.
      Tobacco-withdrawal symptoms, craving for cigarettes, and weight gain in abstinent
      subjects were reduced by the active spray. Minor irritant side-effects were
      frequent in both active and placebo sprays, but only 2 subjects had the spray
      discontinued as a result. No serious adverse effects were encountered. Nasal
      nicotine spray combined with supportive group treatment is an effective aid to
      smoking cessation.

PMID- 1353804
TI  - Randomised study of two doses of cisplatin with cyclophosphamide in epithelial
      ovarian cancer.
AB  - Cisplatin is generally accepted to be the most active cytotoxic agent for the
      treatment of ovarian cancer but the optimum dose remains unclear. We have
      performed a randomised trial to assess the importance of cisplatin dose in the
      treatment of advanced epithelial ovarian cancer. Patients were randomly assigned
      treatment with 50 mg/m2 (low dose) or 100 mg/m2 (high dose) cisplatin plus 750
      mg/m2 cyclophosphamide, for a maximum of six cycles with intervals of 3 weeks. We
      planned to recruit 300 patients, but an interim analysis on the first 165
      indicated a highly significant survival difference (p = 0.0008). Recruitment was
      therefore stopped and the trial patients were followed-up for 12 months longer.
      The relative progression rate (high-dose/low-dose) after 12 months' extra follow
      up was 0.55 (95% confidence interval 0.37-0.81, p = 0.003) and the relative death
      rate 0.53 (0.34-0.81, p = 0.003). Overall median survival was 69 weeks in the low
      dose group and 114 weeks in the high-dose group. Residual disease extent before
      chemotherapy had an important influence--patients with lesions of less than 2 cm
      did best; if given high-dose cisplatin their median survival was 3 years. 56 low
      dose and 45 high-dose patients completed six cycles of chemotherapy; 15 and 9
      patients, respectively, were withdrawn early because of progressive disease and
      treatment was stopped in 6 and 25, respectively, because of unacceptable side
      effects or patient refusal. Toxic effects were significantly greater in the high
      dose group, especially those on the nervous system and ears, alopecia, vomiting,
      and anaemia. Although the higher dose of cisplatin clearly leads to better
      results in terms of survival, its overall clinical benefit in the management of
      ovarian cancer will depend on further improvements in measures to alleviate toxic
      effects.

PMID- 1353805
TI  - Postoperative morbidity among symptom-free alcohol misusers.
AB  - Retrospective studies suggest that there is an increased postoperative morbidity
      among alcohol misusers. We have prospectively studied the risk of alcohol intake
      among patients undergoing surgery. We investigated 15 symptom-free subjects who
      required colorectal surgery and who were drinking at least 60 g of alcohol per
      day. These patients were matched for sex, nutrition, age, weight, cardiovascular
      and pulmonary disease, diagnosis, anaesthesia, and surgery to 15 control subjects
      who were consuming below 25 g of alcohol daily. Those drinking at least 60 g of
      alcohol per day developed more postoperative complications than controls (67% vs
      20%, p less than 0.05) and hospital stay was prolonged (20 vs 12 days, p less
      than 0.05). Preoperatively, alcohol misusers had reduced left ventricular
      ejection fraction (median, 54% vs 68%, p less than 0.01). Delayed
      hypersensitivity responses were smaller in the alcohol group before (53 mm2 vs 78
      mm2, p less than 0.05) and after (18 mm2 vs 55 mm2, p less than 0.01) surgery.
      Alcohol misusers had longer bleeding times during the first postoperative week (p
      less than 0.01). Surgical stress responses, as assessed by changes in plasma
      cortisol and catecholamines, were higher among alcoholics (p less than 0.05).
      Postoperative morbidity is increased in symptom-free alcohol misusers. The
      mechanism is probably subclinical cardiac insufficiency, immunosuppression, and
      decreased haemostatic function. Preoperative alcohol consumption may be a more
      important risk factor than previously thought.

PMID- 1353806
TI  - Prevalence of HIV-1 and HIV-2 mixed infections in Cote d'Ivoire.
AB  - We have investigated the cause of dual serological reactivity to human
      immunodeficiency virus (HIV) types 1 and 2, a common occurrence in West Africa.
      Serum specimens from 111 individuals from Cote d'Ivoire classified by commercial
      western blot as HIV-1 (n = 15), HIV-2 (32), and dually reactive (64) were further
      tested by more specific serological tests (a synthetic peptide enzyme immunoassay
      [Pepti-LAV 1/2] and western blots prepared from antigen in which oligomeric forms
      of the transmembrane protein were disrupted by trichloroacetic acid [WB-TCA]).
      Peripheral blood mononuclear cells were tested for HIV-1 and HIV-2 with the
      polymerase chain reaction (PCR) and virus culture. Of 104 samples that were
      concordant by both WB-TCA and Pepti-LAV, 82 (79%) were confirmed by PCR results.
      Virus culture was concordant with serology for specimens (35/38) in which any
      virus was detected. Our findings indicate that mixed HIV-1/HIV-2 infections are
      common in Cote d'Ivoire, and suggest that natural infection by one HIV type does
      not prevent heterologous infection.

PMID- 1353807
TI  - Virological and polymerase chain reaction studies of HIV-1/HIV-2 dual infection
      in Cote d'Ivoire.
AB  - Dual serological reactivity to the human immunodeficiency virus (HIV) types 1 and
      2 is common in Cote d'Ivoire. To assess whether dual infection is the reason for
      dual seropositivity we sought HIV-1 and HIV-2 proviral DNA in primary uncultured
      peripheral blood mononuclear cells from selected seropositive patients in Cote
      d'Ivoire with the polymerase chain reaction (PCR). PCR on primary lymphocytes in
      36 dually seropositive samples revealed the presence of both HIV-1 and HIV-2
      proviral DNA in 12 cases and the presence of HIV-1 only in 24 cases. In 18 of
      these 36 samples a virus was isolated and identified by PCR. HIV-1 was isolated
      from the 9 specimens with only HIV-1 proviral DNA in the primary lymphocytes.
      Among dually PCR-positive samples, 2 viral isolates reacted with both HIV-1 and
      HIV-2 primers; and only HIV-2 (n = 1) or HIV-1 (n = 6) strains were isolated from
      the other samples. The findings show that surveys based on serology may
      overestimate the prevalence of mixed infections in areas where both HIV-1 and HIV
      2 occur.

PMID- 1353808
TI  - Typhoid vaccination: weighing the options.

PMID- 1353809
TI  - Tumour pH.

PMID- 1353810
TI  - Magnetic resonance imaging in epilepsy.

PMID- 1353811
TI  - On the falsification of ideas.

PMID- 1353812
TI  - When a patient says no.

PMID- 1353813
TI  - Black-white mortality differences by family income.
AB  - Death rates among US black men and women under 75 years of age are higher than
      for their white counterparts. The explanation for this excess risk, though
      attributed to socioeconomic factors, remains unclear. We calculated mortality
      rates by family income for blacks and whites in a representative sample of the US
      population (National Longitudinal Mortality Study). For persons aged less than 65
      years of age, mortality rates are lower in those with higher family income for
      both blacks and whites, and both men and women. However, at each level of income,
      blacks have higher mortality than whites. Higher levels of family income are also
      associated with lower death rates from cardiovascular disease, cancer, and deaths
      from causes other than cardiovascular disease or cancer. After adjustment for
      income, blacks have higher death rates from each of these three general causes.
      For subjects below 65 years, the mortality gradient by income is larger than the
      gradient by race. The differences in mortality rates by race not accounted for by
      income may be due to other differences such as access to health care, type or
      quality of medical care, or behavioral risk factors that disadvantage black
      populations.

PMID- 1353814
TI  - Childhood deaths in Africa: uses and limitations of verbal autopsies.
AB  - The verbal autopsy (VA) is an epidemiological tool that is widely used to ascribe
      causes of death by interviewing bereaved relatives of children who were not under
      medical supervision at the time of death. This technique was assessed by
      comparison with a prospective survey of 303 childhood deaths at a district
      hospital in Kenya where medically confirmed diagnoses were available. Common
      causes of death were detected by VA with specificities greater than 80%.
      Sensitivity of the VA technique was greater than 75% for measles, neonatal
      tetanus, malnutrition, and trauma-related deaths; however, malaria, anaemia,
      acute respiratory-tract infection, gastroenteritis, and meningitis were detected
      with sensitivities of less than 50%. There may have been unwarranted optimism in
      the ability of VAs to detect some of the major causes of death, such as malaria,
      in African children. VA used in malaria-specific intervention trials should be
      interpreted with caution and only in the light of known sensitivities and
      specificities.

PMID- 1353815
TI  - Classical migraine: symptoms between visual aura and headache onset.
AB  - The gap between the end of the visual aura and headache onset in classical
      migraine has been called the free interval. In a retrospective study of twenty
      five migraineurs who had noted a gap, only three reported feeling normal at that
      time: twenty-two described alterations in mood, detachment from the environment
      or other people, fears, disturbances of speech or thought, or somatic symptoms.
      The interval lasted less than an hour in seventeen of the twenty-two but in five
      persisted for 1 to 5 hours. These symptoms suggest involvement of the frontal and
      temporal cortices as well as the hypothalamus; they do not conform to Leao's
      spreading depression or a vascular mechanism, but are in keeping with a diffuse
      cerebral process with focal manifestations.

PMID- 1353816
TI  - The innocent research worker.

PMID- 1353817
TI  - Uncelebrated triumph of dental health.

PMID- 1353818
TI  - France: doctors face charges over HIV-infected blood.

PMID- 1353820
TI  - X-ray mammography and breast compression.

PMID- 1353819
TI  - X-ray mammography and breast compression.

PMID- 1353821
TI  - Emergence of Vibrio cholerae O1 resistant to vibriostatic agent 0/129.

PMID- 1353822
TI  - Sunlight and cholera.

PMID- 1353823
TI  - Comparison of nutrient composition of refugee rations and pet foods.

PMID- 1353824
TI  - Diagnosis of Leber's hereditary optic neuropathy without neurological
      abnormalities.

PMID- 1353825
TI  - Remission of Leber's hereditary optic neuropathy with idebenone.

PMID- 1353826
TI  - Effects of dual-chamber pacing in hypertrophic cardiomyopathy without
      obstruction.

PMID- 1353827
TI  - Effects of dual-chamber pacing in hypertrophic cardiomyopathy without
      obstruction.

PMID- 1353828
TI  - Mitochondrial DNA mutations in the myelodysplastic syndrome.

PMID- 1353829
TI  - Prognostic value of serum beta 2-microglobulin in HIV infection.

PMID- 1353830
TI  - Prognostic value of serum beta 2-microglobulin in HIV infection.

PMID- 1353831
TI  - TNF alpha in stool as marker of intestinal inflammation.

PMID- 1353832
TI  - Tumour metastasis.

PMID- 1353833
TI  - Autoimmune haemolytic anaemia associated with transitional cell carcinoma.

PMID- 1353834
TI  - Paraneoplastic limbic encephalitis presenting as acute viral encephalitis.

PMID- 1353835
TI  - AIDS in Cuba.

PMID- 1353836
TI  - Health of the Nation and back pain.

PMID- 1353837
TI  - Ganglioside therapy and overuse of coadjuvants in Italy.

PMID- 1353838
TI  - Complacency bias in clinical trials.

PMID- 1353839
TI  - Emergence of blinding malnutrition in Iraq.

PMID- 1353841
TI  - Reversible blocking of peripheral inputs and writing in patients with cerebellar
      tremors.

PMID- 1353840
TI  - Randomised consent trials.

PMID- 1353842
TI  - Tests for renal vascular disease.

PMID- 1353843
TI  - Prophylactic insulin.

PMID- 1353844
TI  - Insulin resistance and cigarette smoking.

PMID- 1353845
TI  - Prophylactic insulin.

PMID- 1353846
TI  - Genetics of hypertension.

PMID- 1353847
TI  - Pneumococcal vaccination and travel to Spain.

PMID- 1353848
TI  - Vascular autoantibodies in amyotrophic lateral sclerosis.

PMID- 1353849
TI  - Avoidance of hyperergic reactions after booster tetanus toxoid vaccination.

PMID- 1353850
TI  - Failure of ceftriaxone for amyotrophic lateral sclerosis.

PMID- 1353851
TI  - Secondary leukaemias after etoposide.

PMID- 1353852
TI  - Bradycardia after amphotericin, irradiation, and anthracycline.

PMID- 1353853
TI  - Immunohistochemical study of c-erbB-2 oncoprotein overexpression in human major
      salivary gland carcinoma: an indicator of aggressiveness.
AB  - In order to analyze the correlation between immunohistochemical positivity for c
      erbB-2 oncoprotein and prognosis in patients with malignant salivary gland
      tumors, 59 cases of malignant tumors of the major salivary glands, including 35
      parotid gland, 20 submaxillary gland and 4 sublingual gland tumors, were studied
      immunohistochemically using a polyclonal antibody against c-erbB-2 oncoprotein.
      Positive staining was observed in 13 (22%) of the 59 cases. Interestingly,
      positive results were obtained only in adenocarcinoma (6/20) and carcinoma in
      pleomorphic adenoma (7/15), and not in any other histological types such as
      adenoid cystic carcinoma, mucoepidermoid tumor, and squamous cell carcinoma.
      There was no correlation between the degree of differentiation of adenocarcinoma
      and c-erbB-2 positivity. Since the carcinoma in pleomorphic adenoma positive for
      c-erbB-2 oncoprotein was adenocarcinoma, adenocarcinoma and adenocarcinoma in
      pleomorphic adenoma were placed together (n = 33), and the presence or absence of
      c-erbB-2 oncoprotein in this group was examined for correlation with patients'
      survival and other clinicopathological features, including clinical stage, tumor
      size, surgical margins, and lymph node status. The c-erbB-2-positive tumors
      tended to be more advanced and larger than negative tumors. Similarly, c-erbB-2
      positive tumors were difficult to resect completely, were associated with lymph
      node metastasis more frequently, and showed lower disease-free survival than
      negative cases (P less than .05). We conclude that immunohistochemical positivity
      for c-erbB-2 is an indicator of aggressiveness in both adenocarcinoma and
      adenocarcinoma in pleomorphic adenoma of the major salivary glands.

PMID- 1353854
TI  - Regulation of nerve growth factor and nerve growth factor receptor production by
      NMDA in C6 glioma cells.
AB  - The synthesis of nerve growth factor (NGF) and nerve growth factor receptor
      (NGFR) were studied in a C6 glioma cell line by Northern blot hybridization. In
      response to a glutamate agonist N-methyl-D-aspartic acid (NMDA), NGF mRNA
      increased by up to 2-fold after 4-12 h of culture. The non-NMDA receptor
      agonists, quisqualate and kainate, did not induce any increase of NGF mRNA, and
      kainate actually produced a decrease. The increase in NGF mRNA in response to
      NMDA was dose-dependent at 1, 5 and 10 microM. NGF receptor (NGFR) mRNA showed
      changes in expression which were similar to those for NGF mRNA, but were less
      marked. The specific glutamate antagonist 2-aminophosphonovaleric acid (APV)
      blocked the increase of NGF mRNA produced by NMDA. In the absence of Ca2+, an
      increase of NGF mRNA was still observed but in the presence of 1 mM ethylglycol
      bis-(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA), NGF mRNA production
      abolished. The mechanism producing an increase in NGF mRNA by NMDA may be
      mediated by cyclic AMP since intracellular cyclic AMP and NGF mRNA levels both
      increased following treatment with NMDA or dibutyryl cyclic AMP.

PMID- 1353855
TI  - Modulation of tyrosine hydroxylase gene expression in the rat adrenal gland by
      exercise: effects of age.
AB  - Both aging and exercise are associated with alterations in circulating levels of
      catecholamines. To determine the interactions of age and exercise on tyrosine
      hydroxylase (TH) activity and TH mRNA, Fischer-344 female rats aged 5 months
      (young) and 25 months (old) were trained by treadmill running for 10 weeks. The
      elevation in maximum oxygen consumption in both groups was equivalent following
      exercise, indicating that training had occurred. In control rats, both TH
      activity and TH mRNA were greater in the older groups when compared with the
      younger animals. In young rats, exercise decreased TH activity by 25% and TH mRNA
      by 27%. In older rats, exercise was not associated with a decrease in TH activity
      and TH mRNA. Choline acetyltransferase activity (ChAT) was decreased and glutamic
      acid decarboxylase activity (GAD) was increased by exercise in young rats. The
      decrease in ChAT activity and increase in GAD activity suggest that trans
      synaptic mechanisms play a role in the exercise-induced alteration of TH gene
      expression. Neither ChAT nor GAD was altered by exercise in older groups. Our
      data suggest that the previously reported diminution in catecholamines associated
      with exercise may be due to a decrease in TH mRNA and a resulting decrease in TH
      activity. There was no effect of exercise in the old rats, supporting previous
      observations that the plasticity of the sympathoadrenal system diminishes with
      age.

PMID- 1353858
TI  - Oral mesalamine for ulcerative colitis.

PMID- 1353856
TI  - Molecular aspects of the regulation of tyrosine hydroxylase by testosterone.
AB  - Previous studies have demonstrated that the sympathetic hypogastric ganglia (HG)
      are dependent upon the continued presence of testosterone for normal development
      and maintenance of tyrosine hydroxylase (TH) activity. The regulation of TH by
      testosterone has been examined further to determine whether the reduction in TH
      activity following castration is associated with changes in levels of TH protein
      and mRNA. TH protein was measured by immunotitration of HG homogenates using a TH
      specific antibody, and TH-specific mRNA was detected by hybridization of dot
      blots of total RNA isolated from HG with a cDNA probe coding for TH. The results
      show that tyrosine hydroxylase activity, protein and mRNA are coordinately
      reduced in a graded fashion at 1, 2 and 4 weeks following castration.
      Testosterone replacement therapy immediately following castration prevents the
      decrease in TH levels. The results indicate that gonadal steroids regulate the
      biosynthesis of TH in the HG. Testosterone may control TH either directly by
      interacting with neurons of the HG, or indirectly by altering levels of trophic
      factors in the target tissues.

PMID- 1353857
TI  - Hippocampal neuropeptide Y mRNA is reduced in a strain of learned helpless
      resistant rats.
AB  - The learned helpless rat is considered to be one of the better animal models of
      depression. A genetically inbred strain with a high vulnerability to develop
      helplessness (LH), as well as a highly resistant strain (NLH) have both been
      developed. Since the brain peptide neuropeptide Y (NPY) is involved in the
      regulation of a number of behaviors known to be altered in clinical depression as
      well as in learned helplessness, we measured the relative level of NPY mRNA in
      the hippocampus and cortex of control Sprague Dawley (SD), LH and NLH rats. We
      find that NLH rats have approximately a 30-35% decrease in basal hippocampal NPY
      mRNA compared with SD and LH rats. By contrast, cortical NPY mRNA and hippocampal
      pre-proenkephalin and somatostatin mRNA levels were not significantly different
      in the 3 strains. The data suggest that the regulation of NPY gene expression may
      be involved in the reduced vulnerability of NLH rats to develop learned
      helplessness.

PMID- 1353859
TI  - Media mishandle medical news.

PMID- 1353860
TI  - Correction: a new interpretation of a chicken transforming growth factor-beta 4
      complementary DNA.

PMID- 1353861
TI  - Familial amyloid polyneuropathy related to transthyretin Gly42 in a Japanese
      family.
AB  - A Japanese family is described in which 6 persons showed familial amyloid
      polyneuropathy (FAP). Mean ages of onset were 38 for 4 males and 54 for 2
      females. Three of the 6 became emaciated and died after 4 to 10 years. In 5,
      muscular weakness and autonomic dysfunction were the initial symptoms followed by
      sensory disturbances. Amyloidotic cardiomyopathy was present in 3 of the
      subjects. Amyloid deposits showed an immunohistological relation to transthyretin
      (TTR). Analysis of 1 patient's TTR gene revealed a single base change (A----G)
      that led to amino acid substitution (Glu42----Gly). This base change produced a
      new restriction site for endonuclease Cfr13 I in exon 2. Polymorphic analysis of
      the length of the Cfr13 I-restriction fragment confirmed the base change, and
      made it possible to detect the mutant TTR Gly42 gene in the FAP subjects. Amino
      acid sequencing analysis showed a variant of TTR Gly42 in 1 patient's serum.

PMID- 1353862
TI  - Case of the month: germline mosaicism in carriers of Duchenne muscular dystrophy.
AB  - Carrier testing in a Duchenne muscular dystrophy (DMD) family resulted in the
      identification of a case of germline mosaicism. Using dystrophin cDNA probes,
      this phenomenon was ascertained by the demonstration of a deletion junction
      fragment present in the DNA of the affected patient and one sister but absent in
      the mother's DNA. As a result of this finding carrier risk estimations, based on
      restriction fragment length polymorphism (RFLP) studies, were significantly
      altered. The case demonstrates the importance of cDNA deletion carrier testing
      and the counseling implications of germline mosaicism.

PMID- 1353863
TI  - The mysterious virus called "isn't".

PMID- 1353864
TI  - Development and evolution. Mice and flies head to head.

PMID- 1353865
TI  - Nested expression domains of four homeobox genes in developing rostral brain.
AB  - Insight into the genetic control of the identity of specific regions along the
      body axis of vertebrates has resulted primarily from the study of vertebrate
      homologues of regulatory genes operating in the Drosophila trunk, but little is
      known about the development of most anterior regions of the body either in flies
      or vertebrates. Three Drosophila genes have been identified that are important in
      controlling the development of the head, two of which, empty spiracles and
      orthodenticle, have been cloned and shown to contain a homeobox. We previously
      cloned and characterized Emx1 and Emx2, two mouse genes related to empty
      spiracles that are expressed in restricted regions of the developing forebrain,
      including the presumptive cerebral cortex and olfactory bulbs. Here we report the
      identification of Otx1 and Otx2, which are related to orthodenticle. We have
      compared the expression domains of the four genes in the developing rostral brain
      of mouse embryos at a developmental stage, day 10 post coitum, when they are all
      expressed. Otx2 is expressed in every dorsal and most ventral regions of
      telencephalon, diencephalon and mesencephalon. The Otx1 expression domain is
      similar to that of Otx2, but contained within it. The Emx2 expression domain is
      comprised of dorsal telencephalon and small diencephalic regions, both dorsally
      and ventrally. Finally, Emx1 expression is exclusively confined to the dorsal
      telencephalon. Thus at the time when regional specification of major brain
      regions takes place, the expression domains of the four genes seem to be
      continuous regions contained within each other in the sequence Emx1 less than
      Emx2 less than Otx1 less than Otx2.

PMID- 1353866
TI  - [Tardive dystonia].
AB  - Two patients with tardive dystonia are presented. Tardive dystonia is a late
      onset side effect of dopamine antagonist, which occurs in approximately 2% of the
      patients in the course of treatment with neuroleptic medication. The dystonia
      usually starts by affecting the musculature of face and (or) neck and is often
      progressive to a segmental localization. Of differential diagnostic importance
      are: conversion disorder, acute dystonia, Wilson's disease, idiopathic dystonia
      and dystonia triggered by other agents. Treatment starts with reevaluation of the
      need for ongoing neuroleptic treatment. Investigation of the pharmacotherapy of
      the dystonia concerns mostly treatment with dopamine depletors or with high doses
      of anticholinergic agents. Improvement of 50% of the patients is reported,
      although total recovery is rare. Many other substances and also some physical
      methods (ECT and surgery) have been used with varying results.

PMID- 1353868
TI  - European Dialysis and Transplant Association--European Renal Association XXIXth
      annual congress. Paris, France, 28 June-1 July 1992. Abstracts.

PMID- 1353867
TI  - Lipid and lipoprotein (a) concentrations in renal transplant patients.
AB  - Lipid and lipoprotein concentrations, including lipoprotein (a), were measured in
      67 clinically stable renal allograft recipients and compared with age- and sex
      matched controls. Median lipoprotein (a) concentrations were significantly
      elevated in the transplant group (P = 0.048), with the distribution of apoprotein
      (a) isoforms being similar between the two groups. The transplant group also
      demonstrated significant elevations in cholesterol (P less than 0.0001),
      triglycerides (P = 0.0007) and low-density lipoprotein cholesterol (P less than
      0.0001). There was no significant difference in high-density lipoprotein
      cholesterol concentrations between the groups although there was the expected
      tendency for higher values in females. Lipoprotein abnormalities are common
      following renal transplantation and these patients also demonstrate elevated
      lipoprotein (a) values. This unique lipoprotein is known to be atherogenic and
      may contribute to the development of vascular disease, which is a common mode of
      death in these patients.

PMID- 1353869
TI  - An acquired knowledge about the universe.

PMID- 1353870
TI  - [The reflection of our planet].

PMID- 1353871
TI  - Reactivity of P-glycoprotein monoclonal antibodies in childhood cancers.
AB  - P-Glycoprotein (P-gp), the product of the mdr-1 gene, is implicated in the
      development of chemoresistance in a variety of, mostly adult, cancers. Its role
      in paediatric tumours, most of which are non-epithelial in origin, has yet to be
      fully elucidated. A study was undertaken to investigate reactivity of two P-gp
      monoclonal antibodies (MAbs), JBS-1 and MRK16, recognising cytoplasmic and
      surface epitopes, respectively, of the P-gp molecule, in a variety of newly
      diagnosed and relapsed childhood cancers. P-gp was not expressed in any of 36
      tumours examined (neuroblastoma 13, nephroblastoma 12, rhabdomyosarcoma 6,
      lymphoma 3, teratoma 1, Ewings 1), 14 of whom had chemoresistant disease.
      Reactivity to both MAbs was also investigated in patients with acute leukaemia.
      Out of 10 diagnostic acute lymphoblastic leukaemia (ALL) samples, a positive
      reaction with JSB-1 was observed in 1 patient who failed to remit on standard
      induction therapy and in 3 of 6 patients in ALL relapse, only 1 of whom showed
      low grade positivity with MRK16. Both MAbs reacted positively in 1 patient with
      acute non-lymphocytic leukaemia (ANLL) at diagnosis who achieved remission with
      teniposide and cytosine arabinoside, but relapsed 7 months later and was again
      positive with both Mabs. JSB-1 also showed varying degrees of positivity in 4 out
      of 4 other patients in ANLL relapse. It would therefore appear that P-gp is
      unlikely to mediate chemoresistance in most solid tumours of childhood, but may
      well play a major role in the development of chemoresistance in acute leukaemia.

PMID- 1353872
TI  - [Beta-blockers and migraine].
AB  - Five beta-blocking agents are effective as long-term prophylactic treatment of
      migraine: propranolol, metoprolol, timolol, atenolol and nadolol. Propranolol has
      been most extensively studied and proved effective in 19 of 21 controlled trials.
      The optimal dose should be determined on a case-by-case basis, by increasing the
      daily dosage gradually. Among the properties of beta-blockers, the only one which
      appears to be correlated--albeit negatively--with effectiveness on migraine is
      intrinsic sympathomimetic activity (ISA): drugs without ISA are effective against
      migraine whereas partial agonists are not. The mode of action of beta-blockers in
      migraine is still poorly understood; one of the most cogent current hypotheses
      involves reduction of brain catecholaminergic hyperactivity.

PMID- 1353873
TI  - [Calcium channel blockers and prevention of migraine].
AB  - Calcium antagonists have been proposed for the prophylactic treatment of migraine
      because of their putative vasodilating antispasmodic effect and of their action
      against the cellular consequences of brain hypoxia. Published reports of
      controlled double-blind studies of calcium antagonists for the prophylactic
      treatment of migraine are reviewed herein. The effectiveness of verapamil,
      diltiazem, and nifedipine in this indication cannot be considered as firmly
      demonstrated, when problems with trial design and the amount of available data
      are taken into account. Nimodipine failed to demonstrate significant
      effectiveness in migraine with or without an aura. In contrast, the ability of a
      diphenylpiperazine, flunarizine, to decrease the incidence of migraine attacks in
      patients with common or classical migraine has been firmly demonstrated, although
      there is less evidence of this agent's effectiveness on the duration and severity
      of attacks. The percentage of patients who respond to flunarizine seems
      comparable to the percentages of propranolol or pizotifen responders. However,
      flunarizine is associated with unpleasant (weight gain) or severe (extrapyramidal
      or depressive symptoms) adverse effects which limit its place to that of a second
      line drug. Lastly, the analysis of these studies failed to disclose a correlation
      between calcium movements across the cell membrane and effectiveness for the
      prevention of migraine attacks. Flunarizine's effect in migraine probably
      involves monoamine mechanisms which bear no relation to calcium.

PMID- 1353874
TI  - [Serotonin agonists and antagonists in migraine].
AB  - Serotonin agonists (for the acute treatment of attacks) and antagonists (for
      prophylactic treatment) are the most widely used drugs to treat migraine.
      However, their effectiveness is not complete and their use is limited by side
      effects. The activity and presumptive mode of action of these drugs provide
      support for the role of serotonin in the pathophysiology of migraine and suggest
      that the trigeminal-vascular system is at the center of the attack; however,
      other factors and mechanisms may also be involved.

PMID- 1353875
TI  - Presence of acetyl-transferases and adenylyl-transferases in gentamicin-resistant
      transconjugants.
AB  - The aim of this work was to test the production of aminoglycoside modifying
      enzymes in 20 gentamicin-resistant transconjugants obtained from clinical strains
      of Entero-bacteriaceae. The susceptibility to aminoglycosides was determined by
      disc diffusion method and agar dilution method according to European Committee
      for Clinical Laboratory Standards, 1988. The transfer of gentamicin-resistance R
      plasmids was made by conjugation on a solid medium with recipients E. coli K12.
      Phosphocellulose paper binding assay with 14C acetyl. CoA and 14C.ATP by Haas and
      Dowding was performed to reveal the enzyme production. Four different acetyl
      transferases have been found: AAC/3/I, AAC/3/-V, AAC/3/-IV which modify
      gentamicin, and AAC/6'/-I with activity on amikacin. Only two of the
      transconjugants showed adenylyl-transferase activity:AAD/2"/. Some of strains
      tested possessed two enzymes. The most interesting finding was that the majority
      of strains owned AAC/3/-IV, which modifies apramycin. This was be explained with
      the fact that apramycin is still in a large use for animal husbandry in Bulgaria.
      IN CONCLUSION: four different acetyl-transferases: AAC/3/-I, AAC/3/-V, AAC/3/-IV
      and AAC/6'/-I and the adenylyl-transferase AAD/2"/ were found to be the
      biochemical mechanisms of resistance to aminoglycosides in 20 gentamicin
      resistant transconjugants.

PMID- 1353876
TI  - Gastrointestinal decontamination. Which method is best?
AB  - Why has ipecac syrup become less popular in emergency management of poisoning and
      overdose? When should gastric lavage, activated charcoal, cathartics, or a
      combination of methods be used? Which patients are candidates for whole-bowel
      irrigation with polyethylene glycol-electrolyte solution? Drs Harris and Kingston
      answer these questions and present their recommendations for each of the
      available management options.

PMID- 1353878
TI  - Neu oncogene expression in ovarian tumors: a quantitative study.
AB  - We studied neu mRNA expression by slot blot analysis and protein product
      expression by capture ELISA and immunohistochemistry in 57 primary and metastatic
      ovarian neoplasms, two paraovarian leiomyosarcomas, and eight normal ovaries.
      Some 61% of ovarian tumors but none of the paraovarian neoplasms or normal
      ovaries overexpressed neu mRNA. A total of 96% of the ovarian tumors that
      overexpressed neu were of epithelial type. Epithelial ovarian tumors had
      significantly higher amounts of the neu oncogene product as determined by capture
      ELISA than either germ cell and stromal tumors or normal ovaries (p less than
      0.025). Different subtypes of ovarian carcinomas had significantly different
      amounts of neu oncogene product as measured by capture ELISA; endometrioid tumors
      had the highest, and poorly differentiated carcinomas not otherwise specified had
      the lowest (p less than 0.025). ELISA values, mRNA overexpression, and
      immunohistochemical staining intensity did not correlate with stage at diagnosis
      or architectural or nuclear grade in ovarian tumors. We conclude that capture
      ELISA is a simple, effective way to measure the neu oncogene protein product and
      that there is a good correlation between ELISA levels and immunohistochemical
      staining intensity. However, ELISA values did not correlate with stage or
      histologic prognostic factors in ovarian neoplasms.

PMID- 1353877
TI  - Discerning malignancy in human adrenocortical neoplasms: utility of DNA flow
      cytometry and immunohistochemistry.
AB  - In order to evaluate more objective laboratory methods that may help practicing
      pathologists to discern malignancy in human adrenocortical neoplasms, we have
      examined cellular DNA content by flow cytometry and immunohistochemical
      distribution of c-myc, vimentin, proliferating cell nuclear antigen (PCNA), and
      epidermal growth factor receptor (EGFR) in 15 cases of human adrenocortical
      neoplasms (nine carcinomas and six adenomas). All of these examinations were
      performed on routinely processed surgical pathology specimens. All carcinoma
      cases met Weiss's histologic criteria. Seven of eight adrenocortical carcinomas
      demonstrated aneuploid DNA content, while all adenomas were diploid by flow
      cytometry. c-myc oncoprotein was observed both in cytoplasms and nuclei in all
      carcinomas but only in nuclei in adenomas. Vimentin was present in all carcinoma
      cases examined but was also observed in three of six cases of adenoma. There were
      no clinical or histologic differences between vimentin-positive and vimentin
      negative adenomas. Immunoreactivity of PCNA and EGFR was observed in all the
      cases examined. There were no significant differences in distribution or patterns
      of immunoreactivity between adrenocortical carcinoma and adenoma. Therefore, we
      conclude that only DNA ploidy examined by flow cytometry and immunolocalization
      patterns of c-myc oncoprotein expression have any practical value in the
      pathologic evaluation of adrenocortical neoplasms. Careful morphologic and/or
      clinical studies are still considered to be the best available methods in
      discerning malignancy in resected human adrenocortical neoplasms.

PMID- 1353879
TI  - Delayed acute measles inclusion body encephalitis in a 9-year-old girl:
      ultrastructural, immunohistochemical, and in situ hybridization studies.
AB  - A 9-yr-old girl developed delayed acute measles inclusion body encephalitis,
      which was different from subacute sclerosing panencephalitis (SSPE) in clinical
      course. Measles virus was demonstrated by electron microscopy,
      immunohistochemistry, and in situ hybridization. Contrary to the most previous
      reports, matrix (M) protein was present in the brain, cerebrospinal fluid, and
      serum and was demonstrated by Western blot analysis and in situ hybridization.
      The hybridization was performed by a nonradioactive digoxigenin method.

PMID- 1353880
TI  - c-erbB-2 expression in primary gastric carcinomas and their metastases.
AB  - In an attempt to evaluate the relationship between c-erbB-2 expression and/or
      gene amplification, DNA ploidy and morphology, wall penetration, lymphatic
      permeation, and vascular invasion, we studied a series of 87 primary gastric
      carcinomas and their respective metastases (n = 335) using immunohistochemistry
      and performed DNA analysis of 30 primary tumors and 10 metastases from eight
      cases. Flow cytometry of fresh or frozen material was performed in 79 primary
      tumors. Five out of 87 primary tumors (5.7%) and 17 out of 335 lymph node
      metastases (5.1%) showed unequivocal membrane immunostaining for c-erbB-2. Seven
      out of 30 primary tumors (23.3%) showed gene amplification while amplification
      was identified in four out of 10 metastases (40.0%) from three patients. Eight
      tumors (9.2%) showed c-erbB-2 protein immunoreactivity, gene amplification, or
      both. One of these cases showed c-erbB-2 protein immunoreactivity only in the
      metastatic deposits, while gene amplification could be identified in the primary
      tumor. Three primary tumors showed gene amplification, but immunoreactive cells
      could not be identified. In no case was protein overexpression identified in the
      absence of gene amplification. Five cases with c-erbB-2 expression/amplification
      were well/moderately differentiated, and all the eight cases with c-erbB-2
      expression/amplification disclosed aggressive features. Lymphatic
      permeation/lymph node metastases were found in all the cases and seven cases
      showed vascular invasion as well. In one case, there was also a liver metastasis.
      Two cases were early gastric carcinomas (T1sm) showing lymphatic permeation/nodal
      metastases and venous invasion. Six cases were aneuploid.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1353881
TI  - Nucleolar organizer regions in human esophageal disorders: comparison with
      proliferating cell nuclear antigen by immunostaining.
AB  - A silver colloid technique to demonstrate nucleolar organizer region-associated
      proteins (AgNORs) was performed on sections of 15 samples of human esophageal
      tissue, including five nonpathological esophageal epithelium, two esophageal
      dysplasia of the squamous epithelium, and eight esophageal squamous cell
      carcinomas. Initially we examined various protocols for AgNOR staining. Staining
      performed on 4% paraformaldehyde-fixed paraffin-embedded specimens with an
      incubation time of 30 min yielded the most satisfactory results. In
      nonpathological esophageal epithelium, the mean number of AgNOR counts per
      nucleus in the four layers of esophageal epithelium was greatest in the parabasal
      layer and was statistically significant. No significant differences were observed
      among the mean number of AgNOR counts per nucleus in the nonpathological
      parabasal layer, dysplasia, and carcinoma. Positive correlation was observed
      between the PCNA labeling index of esophageal disorders and the mean number of
      AgNOR particles per nucleus. Therefore, in esophageal disorders, the AgNOR
      staining per nucleus appears to correlate with proliferative activity but is of
      little practical value in discerning malignancy and/or aggressive biological
      behaviors.

PMID- 1353882
TI  - Contribution of trans-acting factor alleles to normal physiological variability:
      vitamin D receptor gene polymorphism and circulating osteocalcin.
AB  - Osteocalcin, the most abundant noncollagenous protein in bone, is a marker of
      bone turnover in normal and disease states. Its synthesis is induced by
      calcitriol, the active hormonal form of vitamin D, through the vitamin D receptor
      and a specific vitamin D-responsive element in the osteocalcin gene promoter.
      Serum concentrations of osteocalcin are under strong genetic influence. To
      ascertain whether variability in circulating osteocalcin levels may reflect
      allelic variation in the vitamin D receptor gene, we have analyzed the
      relationship between frequent restriction fragment length polymorphisms (RFLPs,
      detected by endonucleases Bsm I, EcoRV, and Apa I) that define human vitamin D
      receptor alleles and serum osteocalcin in a cohort of normal subjects. In 91
      Caucasian subjects, RFLPs in the vitamin D receptor gene predicted circulating
      osteocalcin levels (P less than 0.0001) independent of age or menopause effects.
      Since the osteocalcin gene and the vitamin D receptor gene are encoded on
      different chromosomes, the interaction between these two genes occurs in trans.
      Thus, common alleles of this trans-acting factor, the vitamin D receptor, are
      functionally different and contribute to "normal" physiological variability in
      osteocalcin levels. Preliminary analysis in monozygotic and dizygotic twin pairs
      indicates that the greater diversity in lumbar spine density between the
      dizygotic pairs can be explained by divergence in vitamin D receptor alleles.
      Variations in this receptor and other transacting factor genes may confound
      physiological studies of regulation of target genes and will need to be
      considered in future human and animal studies. This approach to genetic analysis
      provides a paradigm for the study of functional variation in trans-acting factors
      and the role such variation may play in the generation and evolution of
      physiological diversity.

PMID- 1353883
TI  - Chemical modification of Glu-953 of the alpha chain of Na+,K(+)-ATPase associated
      with inactivation of cation occlusion.
AB  - We have investigated the role, number, and identity of glutamate (or aspartate)
      residues involved in cation occlusion on Na+, K(+)-ATPase, using the carboxyl
      reagent N,N'-dicyclohexylcarbodiimide (DCCD). Extensive use is made of
      selectively trypsinized Na+,K(+)-ATPase--the so-called "19-kDa membranes"-
      containing a 19-kDa COOH-terminal, smaller (8-11 kDa) membrane-embedded fragments
      of the alpha chain, and a largely intact beta chain; these membranes have normal
      Rb+ and Na+ occlusion capacities. The 19-kDa peptide and a smaller (approximately
      9 kDa) unidentified peptide(s) are labeled by [14C]DCCD in a Rb(+)-protectable
      fashion. Rb(+)-protected [14C]DCCD incorporation into the "19 kDa membranes" and
      into native Na+,K(+)-ATPase is linearly correlated with inactivation of Rb+
      occlusion. Similar linear correlations are observed when Rb(+)-protected
      [14C]DCCD incorporation is measured by examination of labeling of 19-kDa peptide
      purified from "19-kDa membranes" or of alpha chain purified from native enzyme.
      Stoichiometries, estimated by extrapolation, are as follows: (for "19-kDa
      membranes") close to one DCCD per Rb+ site and one DCCD per 19-kDa peptide; and
      (for native enzyme) close to two DCCD per phosphoenzyme and two DCCD per alpha
      chain. We suggest that each of two K+ (or Na+) sites contains a carboxyl group,
      one located in the 19-kDa peptide and one elsewhere in the alpha chain. After
      cyanogen bromide digestion of purified, labeled alpha chain, or of 19-kDa
      peptide, a labeled fragment of apparent M(r) approximately 4 kDa was detected and
      was identified as that with NH2-terminal Lys-943. Rb(+)-protected [14C]DCCD
      incorporation was associated almost exclusively with Glu-953. We suggest that the
      cation occlusion "cage" consists of ligating groups donated by different trans
      membrane segments and includes two carboxyl groups such as Glu-953 (and perhaps
      Glu-327) as well as neutral groups, in two K+ (or Na+) sites, but only neutral
      groups in the third Na+ site.

PMID- 1353884
TI  - A role for microtubules in sorting endocytic vesicles in rat hepatocytes.
AB  - The vectorial nature of hepatocyte receptor-mediated endocytosis (RME) and its
      susceptibility to cytoskeletal disruptors has suggested that a polarized network
      of microtubules plays a vital role in directed movement during sorting. Using as
      markers a well-known ligand, asialoorosomucoid, and its receptor, we have
      isolated endocytic vesicles that bind directly to and interact with stabilized
      endogenous hepatocyte microtubules at specific times during a synchronous,
      experimentally initiated, single wave of RME. Both ligand- and receptor
      containing vesicles copelleted with microtubules in the absence of ATP but did
      not pellet under similar conditions when microtubules were not polymerized. When
      5 mM ATP was added to preparations of microtubule-bound vesicles, ligand
      containing vesicles were released into the supernatant, while receptor-containing
      vesicles remained immobilized on the microtubules. Release of ligand-containing
      vesicles from microtubules was prevented by monensin treatment during the
      endocytic wave. Several proteins, including the microtubule motor protein
      cytoplasmic dynein, were present in these preparations and were released from
      microtubule pellets by ATP addition concomitantly with ligand. These results
      suggest that receptor domains within the endosome can be immobilized by
      attachment to microtubules so that, following monensin-sensitive dissociation of
      ligand from receptor, ligand-containing vesicles can be pulled along microtubules
      away from the receptor domains by a motor molecule, such as cytoplasmic dynein,
      thereby delineating sorting.

PMID- 1353886
TI  - The A alpha mating locus of Schizophyllum commune encodes two dissimilar
      multiallelic homeodomain proteins.
AB  - The A alpha mating locus is one of four multiallelic loci that govern sexual
      development in the basidiomycete fungus Schizophyllum commune. We have determined
      the nucleotide sequence encoding three A alpha mating types, A alpha 1, A alpha
      3, and A alpha 4. We have found that the locus for A alpha 3 and A alpha 4
      consists of two genes: Y and Z. The locus for A alpha 1 encodes only one gene, Y.
      The Z polypeptides encoded by different alleles exhibit 42% identity. The Y
      polypeptides exhibit 49-54% identity. The finding that the deduced Z and Y
      polypeptides have homeodomain motifs suggests that these polypeptides may be DNA
      binding regulatory proteins that control the expression of developmental genes.
      The deduced Z polypeptide also has acidic regions that might be functionally
      analogous to the acidic regions in yeast GAL4 and GCN4 that activate
      transcription. The Y polypeptide has a serine-rich region and a basic region that
      shows some identity to the lysine-rich region of H1 histones.

PMID- 1353885
TI  - Dopamine transporter mRNA content in human substantia nigra decreases
      precipitously with age.
AB  - The dopamine transporter is the primary means of inactivating synaptic dopamine
      as well as a major site of action for psychostimulants (such as cocaine and
      amphetamine) and for neurotoxins that induce parkinsonism. In the present study,
      a human dopamine transporter partial cDNA clone obtained by polymerase chain
      reaction exhibited 87% and 89% identity at the nucleic acid and amino acid
      levels, respectively, with transmembrane domains 3-5 of the rat homolog. This
      clone was used to quantitate human dopamine transporter mRNA by nuclease
      protection assay. The postmortem content of dopamine transporter mRNA in the
      substantia nigrae of 18- to 57-yr-old subjects was relatively constant, while in
      subjects greater than 57 yr old, a precipitous (greater than 95%) decline in
      substantia nigra dopamine transporter mRNA was evident. In contrast, tyrosine
      hydroxylase mRNA in the same samples declined in a linear manner with increasing
      age. In situ hybridization experiments confirmed the profound loss of dopamine
      transporter gene expression in melanin-positive (presumptive dopamine) nigral
      neurons. These data may begin to shed light on compensatory changes occurring in
      human dopamine neurons during normal aging.

PMID- 1353887
TI  - Functional analysis of the homeodomain-related proteins of the A alpha locus of
      Schizophyllum commune.
AB  - DNA-mediated transformation was used to correlate function with putative genes
      from three alternative A alpha mating-type loci (A alpha 1, A alpha 3, and A
      alpha 4) of Schizophyllum commune. Each DNA was tested in at least nine haploid
      strains, one for each of the nine A alpha mating types found in the world-wide
      population of S. commune. The Y and Z genes (tentatively identified by sequence
      analysis elsewhere) individually activate A alpha-regulated development when
      transformed into any strain with a different A alpha mating type. The only
      exceptions are when the Y alleles of A alpha 3 or A alpha 4 (i.e., Y3 or Y4,
      respectively) are introduced into an A alpha 1 strain (the A alpha 1 locus
      encodes Y1 but lacks a Z gene). These observations indicate that A alpha
      regulated development is activated by the interaction (direct or indirect) of
      products from different genes (e.g., Z3 and Y1) rather than from different
      alleles of the same gene (e.g., Y1 and Y3). Therefore, the activating interaction
      is of the form ZiYj where i not equal to j and i and j are the A alpha mating
      types from which the Z and Y polypeptides, respectively, are derived.
      Transformations with truncated or mutagenized genes begin to define essential
      regions of the genes and their products. Activity is in some cases dependent upon
      the particular A alpha mating type of the recipient. A working hypothesis for the
      activation of A alpha-regulated development is proposed.

PMID- 1353888
TI  - A distinct cytoplasmic domain of CD2 regulates ligand avidity and T-cell
      responsiveness to antigen.
AB  - The T-cell glycoprotein CD2 not only contributes to intercellular adhesion but
      also plays a direct role in T-cell activation. Here we demonstrate that the
      interaction of CD2 with its ligand lymphocyte function-associated antigen 3
      (CD58) is regulated by T-cell receptor-CD3 signaling. T-cell receptor-CD3
      crosslinking by specific antigen or monoclonal antibodies rapidly increases the
      avidity with which cell-surface CD2 binds immunoaffinity-purified CD58.
      Mutational analysis of the CD2 cytoplasmic domain demonstrates that the carboxyl
      terminal asparagine is essential for T-cell receptor-induced changes in CD2
      avidity but is not essential for CD2-mediated signaling, establishing that the
      cytoplasmic portion of CD2 consists of distinct functional domains. Furthermore,
      cell lines expressing CD2 molecules incapable of avidity regulation exhibit a
      marked deficiency in an antigen-specific response. Thus, the regulation of CD2
      adhesiveness has a profound effect on the ability of CD2 to enhance antigen
      responsiveness. These observations demonstrate that adhesion strengthening
      resulting from increased CD2 avidity contributes directly to T-cell
      responsiveness independently of CD2-mediated signal transduction.

PMID- 1353889
TI  - Cloning, expression, and localization of a rat brain high-affinity glycine
      transporter.
AB  - A cDNA clone encoding a glycine transporter has been isolated from rat brain by a
      combined PCR and plaque-hybridization strategy. mRNA synthesized from this clone
      (designated GLYT1) directs the expression of sodium- and chloride-dependent, high
      affinity uptake of [3H]glycine by Xenopus oocytes. [3H]Glycine transport mediated
      by clone GLYT1 is blocked by sarcosine but is not blocked by methyl
      aminoisobutyric acid or L-alanine, a substrate specificity similar to that
      described for a previously identified glycine-uptake system called system Gly. In
      situ hybridization reveals that GLYT1 is prominently expressed in the cervical
      spinal cord and brainstem, two regions of the central nervous system where
      glycine is a putative neurotransmitter. GLYT1 is also strongly expressed in the
      cerebellum and olfactory bulb and is expressed at lower levels in other brain
      regions. The open reading frame of the GLYT1 cDNA predicts a protein containing
      633 amino acids with a molecular mass of approximately 70 kDA. The primary
      structure and hydropathicity profile of GLYT1 protein reveal that this protein is
      a member of the sodium- and chloride-dependent superfamily of transporters that
      utilize neurotransmitters and related substances as substrates.

PMID- 1353892
TI  - Regionally selective deficits in uptake sites for glutamate and gamma
      aminobutyric acid in the basal ganglia in schizophrenia.
AB  - In a post-mortem study of schizophrenic and control subjects, the sodium
      dependent binding of D-[3H]aspartate and [3H]nipecotic acid were used to
      investigate uptake sites of glutamate and gamma-aminobutyric acid (GABA),
      respectively, in subcortical brain regions. Binding to the glutamate uptake site
      was substantially reduced in both the putamen and lateral pallidum of the
      schizophrenic subjects. Binding to the GABA uptake site was substantially reduced
      in the putamen; smaller reductions were apparent in the caudate nucleus and
      lateral pallidum. The results suggest that glutamatergic and GABAergic mechanisms
      in the basal ganglia are abnormal in schizophrenia. These abnormalities could be
      relevant to the development of psychosis but could also relate to the spectrum of
      mild motor disturbances often described in the disease.

PMID- 1353890
TI  - Dermorphin-related peptides from the skin of Phyllomedusa bicolor and their
      amidated analogs activate two mu opioid receptor subtypes that modulate
      antinociception and catalepsy in the rat.
AB  - Three naturally occurring dermorphin-like peptides from the skin of the frog
      Phyllomedusa bicolor, the related carboxyl-terminal amides, and some substituted
      analogs were synthesized, their binding profiles to opioid receptors were
      determined, and their biological activities were studied in isolated organ
      preparations and intact animals. The opioid binding profile revealed a very high
      selectivity of these peptides for mu sites and suggested the existence of two
      receptor subtypes, of high and low affinity. The peptides tested acted as potent
      mu opioid agonists on isolated organ preparations. They were several times more
      active in inhibiting electrically evoked contractions in guinea pig ileum than in
      mouse vas deferens. When injected into the lateral brain ventricle or peritoneum
      of rats, the high-affinity-site-preferring ligand, [Lys7-NH2]dermorphin, behaved
      as a potent analgesic agent. By contrast, the low-affinity-site-preferring
      ligand, [Trp4,Asn7-NH2]dermorphin, produced a weak antinociception but an intense
      catalepsy.

PMID- 1353893
TI  - [A possible role of neuroimmunoendocrine interactions and development of post
      irradiation pathology].
AB  - On the basis of the literature a postulate is proposed that the immune system
      contributes to regulating the intensity and direction of endocrine and nervous
      system functions in normal conditions and after the effect of ionizing radiation.
      The role of neuroimmunoendocrine interactions and their impairment in the
      realization of stochastic and nonstochastic sequelae of irradiation at various
      levels of radiation affecting the organism under normal conditions and in a
      combination with other unfavourable factors.

PMID- 1353891
TI  - Two distinct mechanisms alter p53 in breast cancer: mutation and nuclear
      exclusion.
AB  - Twenty-seven cases of inflammatory breast cancer were screened for the presence
      of the p53 protein by immunocytochemical methods using a monoclonal antibody
      directed against the p53 protein. Three groups were detected: 8 cases (30%) had
      high levels of p53 in the nucleus of the cancer cells; 9 cases (33%) had a
      complete lack of detectable staining; 10 cases (37%) showed a pattern of
      cytoplasmic staining with nuclear sparing. Nucleotide sequence analysis of p53
      cDNAs derived from the samples with cytoplasmic staining revealed only wild-type
      p53 alleles in 6 out of 7 cases. An eighth case was determined to be wild type by
      a single-strand conformation polymorphism. In contrast, the samples containing
      nuclear p53 contained a variety of missense mutations and a nonsense mutation.
      The p53 cDNAs from 3 of the tumors that lacked detectable p53 staining were
      analyzed, and all 3 had wild-type nucleotide sequences. Interestingly, a case of
      normal lactating breast tissue also showed intense cytoplasmic staining for p53
      with nuclear sparing. These data suggest that some breast cancers that contain
      the wild-type form of p53 protein may inactivate its tumor-suppressing activity
      by sequestering this protein in the cytoplasm, away from its site of action in
      the cell nucleus. The detection of cytoplasmic p53 in normal lactating breast
      tissue could suggest that this is the mechanism employed in specific
      physiological situations to permit transient cell proliferation. This observation
      could explain how some breast cancer tissues inactivate p53 function without
      mutation.

PMID- 1353894
TI  - [Neuromediator adaptation of the cerebral cortex and brain stem structures after
      radiation exposure].
AB  - In experiments with male Wistar rats a decreased receptor binding of 3H
      corticosterone and impairment of neuromediator adaptation in the brain structures
      responsible for the regulation of animal and vegetative functions were observed 6
      months after the effect of external radiation (0.5 Gy) and a mixture of external
      radiation and 131I (6.5 microCi/kg). These processes, being partly arrested by
      neurotropin, lay the neurochemical basis for the development of diencephalic
      syndrome.

PMID- 1353895
TI  - Culture of neuronal cells from postnatal rat brain: application to the study of
      neurotrophic factors.
AB  - 1. The authors developed a primary culture technique for neuronal cells from
      postnatal rat brains and studied the effects of neurotrophic factors on the
      naturally developed neurons. 2. We demonstrated changes in the neurotrophic role
      of nerve growth factor (NGF) during the developmental stages of the rat: NGF was
      shown to act as a differentiation factor in the early stages and as a survival
      factor later. 3. It appeared that interleukin-6 (IL-6) supported the survival of
      septal cholinergic neurons obtained from 10-day-old rats. IL-6, however, did not
      induce the differentiation of embryonic rat septal cholinergic neurons. IL-6
      improved the survival of mesencephalic catecholaminergic neurons from postnatal
      and embryonic rat brains, which have known not to be response to NGF.

PMID- 1353897
TI  - Neuroleptic-induced movement disorders and body iron status.
AB  - 1. The distribution of iron in the human brain, what is known about its
      biological functions, and the interaction of neuroleptics with iron suggest that
      this trace metal may play an important role in the pathogenesis of neuroleptic
      induced movement disorders (NIMD). 2. The availability of magnetic resonance
      imaging has made some of the hypotheses testable in human subjects. 3. This
      article is a brief overview of the current literature on the association between
      NIMD and brain iron.

PMID- 1353898
TI  - [Current aspects of extrapyramidal disorders].
AB  - Within the past decade, the harmonious anatomic aspect of the basal ganglia has
      changed for inhomogeneous structures filled up with a wealth of neurotransmitters
      and receptor subtypes with massive vertical and horizontal interconnections,
      asking for new mathematical concepts like parallel distributed processing of
      computation to approach their respective functions. Moreover, not only the motor
      control, but also some important aspects of cognition, eye motions, and limbic
      functions seem to be processed in the basal ganglia. Their overall threshold of
      activity seems to be under the bipolar control of the substantia nigra and the
      subthalamic nucleus; this results in hyper or hypokinetic syndromes. Few
      practical or therapeutical results have come out from the last radiological
      technologies and biochemical studies of extrapyramidal disorders, but the wealth
      of information brings hope for new issues from the knowledge in molecular
      biology, neuropharmacology, and from earlier diagnosis of these diseases in the
      future.

PMID- 1353899
TI  - [Tall statures. Somatostatin analogs against centimeters].

PMID- 1353896
TI  - Social phobia: biological aspects and pharmacotherapy.
AB  - 1. Social phobia is one of the anxiety disorders that until recently, had not
      been thoroughly investigated. 2. Social phobia is a relatively common anxiety
      disorder that appears to have a genetic basis. 3. There are certain physiological
      aspects of social phobia that separate it from the other anxiety disorders. 4.
      Support for a dopaminergic abnormality related to social phobia is supported by
      investigation studies and pharmacotherapy. 5. There are a number of studies
      reporting success in the treatment of social phobia with medications.

PMID- 1353900
TI  - [Recent progresses in the biology of schizophrenia].
AB  - Investigations designed to improve our understanding of the physiopathology of
      schizophrenia are progressing along various, but no necessarily exclusive, lines.
      The most important aspects of the recently established biological data and their
      potential value are discussed and compared to classical hypotheses and results.

PMID- 1353901
TI  - Sulphasalazine therapy in rheumatoid arthritis. A two-year study and follow-up of
      clinical results.
AB  - Sulphasalazine is among the many drugs in the secondary line of antirheumatic
      efficacy that have both immunosuppressive and auto-inflammatory properties.
      Twenty-six patients with definite rheumatoid arthritis (RA) were treated for two
      years with sulphasalazine in a minimum dose of 1 g per day. Four patients
      presented untoward effects such as: marked physical asthenia, erythema and
      changes of the dysproteinemia tests which all disappeared when the drug was
      withdrawn. The first favourable results in the joint inflammation appeared after
      4 weeks. Significant clinical and biologic changes were observed at the end of
      the study thus suggesting the therapeutic value of sulphasalazine in RA.

PMID- 1353902
TI  - Pharmacologic treatment of bladder hyperactivity after augmentation and
      substitution enterocystoplasty.

PMID- 1353903
TI  - [Guided tissue regeneration].

PMID- 1353904
TI  - New virus reports roil AIDS meeting.

PMID- 1353905
TI  - Calcium-dependent transmitter secretion reconstituted in Xenopus oocytes:
      requirement for synaptophysin.
AB  - Calcium-dependent glutamate secretion was reconstituted in Xenopus oocytes by
      injecting the oocyte with total rat cerebellar messenger RNA (mRNA). Co-injection
      of total mRNA with antisense oligonucleotides to synaptophysin message decreased
      the expression of synaptophysin in the oocyte and reduced the calcium-dependent
      secretion. A similar effect on secretion was observed for oocytes injected with
      total mRNA together with an antibody to rat synaptophysin. These results indicate
      that synaptophysin is necessary for transmitter secretion and that the oocyte
      expression system may be useful for dissecting the molecular events associated
      with the secretory process.

PMID- 1353907
TI  - [The 1st Seminar on Bioethics].

PMID- 1353906
TI  - [Theoretical models and the crisis of identity in Portuguese nursing].

PMID- 1353908
TI  - [The "Geriatric Care" Seminar. 19, 20 and 21 February 1992].

PMID- 1353909
TI  - [The terminal patient].

PMID- 1353910
TI  - A mutation in codon 717 of the CHO-K1 elongation factor 2 gene prevents the first
      step in the biosynthesis of diphthamide.
AB  - The histidine residue at position 715 of elongation factor 2 (EF-2) is
      posttranslationally modified in a series of enzymatic reactions to 2-[3
      carboxyamido-3-(trimethylammonio)-propyl]histidine, which has been given the
      trivial name diphthamide. The diphthamide residue of EF-2 is the target site for
      ADP ribosylation by diphtheria toxin and Pseudomonas exotoxin A. ADP-ribosylated
      EF-2 does not function in protein synthesis. EF-2 that has not been
      posttranslationally modified at histidine 715 is resistant to ADP ribosylation by
      these toxins. In this report we show that a G-to-A transition in the first
      position of codon 717 of the EF-2 gene results in substitution of arginine for
      glycine and prevents addition of the side chain of diphthamide to histidine 715
      of EF-2. EF-2 produced by the mutant gene is fully functional in protein
      synthesis.

PMID- 1353911
TI  - The significance of HLA-DRB1 matching in clinical renal transplantation.
AB  - We analyzed the genotype for HLA-DRB1 alleles by digestion of polymerase chain
      reaction-amplified genes with the restriction endonucleases (PCR-RFLP) method to
      investigate the influence of HLA-DR antigen "splits" at the DRB1 gene level on
      the incidence of acute graft rejection in the renal transplant. For all patients,
      the incidence of acute rejection was proportional to the number of the
      serological HLA mismatch (0% in patients with two-haplotype match; 18% with HLA
      A, -B, and -DR zero mismatch; 33% with HLA-DR zero mismatch; and 48% with HLA-DR
      one mismatch). For the patients with serological HLA-DR zero mismatch, the
      incidence of acute rejection in patients with HLA-DRB1 one mismatch (10/13: 77%)
      was significantly higher than that in those with zero mismatch (2/27: 7%). It was
      concluded that genotyping for HLA-DRB1 alleles would be beneficial in predicting
      acute rejection in patients with serological HLA-DR zero mismatch, although no
      difference was noted in the graft survivals.

PMID- 1353912
TI  - Mediation of skin allograft rejection in scid mice by CD4+ and CD8+ T cells.
AB  - We analyzed the role of CD4+ and CD8+ T cells in H-2-disparate skin allograft
      rejection in the mutant mouse strain C.B-17/Icr scid with severe combined
      immunodeficiency. On the day of skin allografting, scid mice were adoptively
      transferred with negatively selected CD4+ or CD8+ splenocytes from normal
      unsensitized C.B-17/Icr mice. These populations were obtained using a double-mAb-
      plus--complement elimination protocol using anti-CD4 or anti-CD8 mAb that
      resulted in no detectable CD4+ or CD8+ cells by FACS and negligible numbers of
      cytolytic T lymphocytes by limiting dilution analysis in anti-CD8 treated
      populations. Spleen cells were removed from grafted mice at the time of rejection
      and were tested in vitro for antidonor reactivity in several assays: mixed
      lymphocyte culture, cell-mediated lympholysis, and LDA for CTL and for IL-2
      producing HTL. The presence of Thy 1.2+, CD4+, or CD8+ cells was determined by
      FACS. All control C.B-17 mice and scid mice adoptively transferred with
      nondepleted CD4+, and CD8+ cells rejected skin allografts with similar mean
      survival times (15.6 +/- 1.5, 18.8 +/- 3.4, 18.0 +/- 5.4, respectively), whereas
      control scid mice retain skin allografts indefinitely (all greater than 100
      days). C.B-17 syngeneic grafts survived indefinitely in all groups. At the time
      of rejection, splenocytes from scid mice receiving CD4+ cells had negligible
      donor-specific cytotoxicity in CML and negligible numbers of CTL by LDA, but
      demonstrated a good proliferative response in MLC and IL-2-producing cells by LDA
      (frequency = 1/1764). There were no detectable CD8+ cells present by FACS
      analysis. Conversely, splenocytes from scid mice adoptively transferred with CD8+
      cells had strong donor-specific cytotoxicity in CML (58.8% +/- 16.1%) and CTL by
      LDA (frequency = 1/3448), but no significant proliferation was detected in MLC.
      There were no detectable CD4+ cells by FACS, but there were small numbers of IL-2
      producing cells by LDA (frequency = 1/10,204). These data demonstrate that CD4+
      cells adoptively transferred into scid mice are capable of mediating skin
      allograft rejection in the absence of any detectable CD8+ cells or significant
      functional cytolytic activity. The adoptive transfer of CD8+ cells also results
      in skin allograft rejection in the absence of detectable CD4+ cells. The
      detection of small numbers of IL-2 secreting cells in these mice may indicate
      that CD(8+)-mediated allograft rejection in this model is dependent on IL-2
      secreting CD8+ cells.

PMID- 1353913
TI  - Prolongation of allograft and xenograft survival in mice by anti-CD2 monoclonal
      antibodies.
AB  - Anti-CD2 monoclonal antibodies (mAb) were used to influence graft survival in two
      transplantation models. Xenogeneic rat islets were transplanted intraportally
      into mice. Anti-CD2 mAb prolonged xenograft survival and was synergistic with UVB
      irradiation in prolonging survival. Anti-CD2 mAb was also more potent than an
      anti-CD4 mAb in this model. Allogeneic cardiac grafts were transplanted across an
      entire H-2 difference and anti-CD2 mAb prolonged allograft survival in a dose
      dependent fashion. Kinetic experiments revealed that anti-CD2 mAb was most potent
      when administered at the time of allografting. A delay in administration of mAb
      markedly reduced its immunosuppressive effects. Furthermore, additional doses of
      mAb given after the initial doses provided no increased immunosuppression and
      anti-CD2 mAbs did not delay rejection of second-set allografts. These findings
      support the notion that anti-CD2 mAbs interfere with afferent immunity and that
      CD2 is most important during the initial steps of an immune response.
      Investigation of the effect of anti-CD2 mAb on cellular immune functions
      demonstrated, in agreement with previous results, that it caused antigenic down
      modulation of CD2 with relative sparing of CD3, CD4, and CD8 cell surface
      expression. Concomitantly the MLR, CTL, and NK responses were suppressed.

PMID- 1353914
TI  - Evidence that therapeutic strategies targeted at CD4+ cells modulate accelerated
      rejection of cardiac allografts in sensitized rats by different mechanisms.
AB  - (LEW x BN)F1 cardiac allografts are rejected within 36 hr in LEW rats
      presensitized with BN skin grafts 7 days earlier (acute rejection occurs within 8
      days). We have previously described the effects of individual CD4 (BWH-4), CD25
      (IL-2R, ART-18) mAbs, and CsA therapeutic regimens upon cardiac allograft
      survival in sensitized hosts. The present studies were designed to probe an
      adjunctive use of ART-18 or CsA upon BWH-4-mediated suppression of accelerated
      graft injury. Sequential therapy with BWH-4 and ART-18 in the sensitization phase
      (days -7 to -1) and effector phase (from day 0, the day of cardiac transplant),
      respectively, prolonged graft survival additively to c. 22 days. Treatment with
      BWH-4 markedly diminished host humoral response against ART-18 preparation. BWH-4
      given in concert with subtherapeutic dose of CsA produced graft survival
      comparable to that induced by mAb alone (c. 13 days) with concomitant decreased
      host anti-BWH-4 response. None of the combined regimens affected the frequency of
      circulating CD4+ cells, as compared with that exerted by BWH-4 monotherapy. Thus
      this study defines principles and some mechanistic aspects of optimal
      immunosuppressive strategies potentiating the effects of CD4-targeted therapy.

PMID- 1353915
TI  - T cell subsets required for in vivo and in vitro responses to single and multiple
      minor histocompatibility antigens.
AB  - The requirement for helper T cells in the in vivo and in vitro T cell response to
      a diverse panel of minor histocompatibility antigens in mice was investigated.
      Target H antigens included: (a) multiple antigens distinguishing H-2-matched,
      inbred strains, and (b) single H antigens, including H-4, H-3, and the male
      specific (H-Y) antigen. The involvement of helper T cells in skin allograft
      rejection and CTL priming was evaluated by pretreating graft recipients with anti
      CD4 antibody. Anti-CD4 treatment had no effect on rejection of H-3- and H-4
      incompatible skin grafts, but slowed rejection of male and BALB.B skin grafts.
      Comparable pretreatment with anti-CD4 antibody in vivo eliminated the priming of
      H-4-specific CTL, multiple B10.BR anti-CBA/J CTL, and all but a minor C57BL/6
      anti-BALB.B CTL population. However, CTL specific for the two classes of H
      antigens, single and multiple minor H antigens, differed in their in vitro
      requirements for CD4+ helper T cells: (a) multiple antigen-specific CTL required
      CD4+ helper T cells for optimal expansion, and (b) CTL specific for single H
      antigens expanded in the absence of helper T cells. The CTL specific for all
      tested H antigens were CD8+ T cells. These results suggest that CD4+ helper T
      cells are not always required for effective skin allograft rejection or CTL
      expansion in vitro; the requirement for helper T cells is apparently dependent
      upon the identity of the stimulatory minor H antigen(s). This variable dependency
      contrasts with the evident requirement for helper T cells in the in vivo priming
      of CTL specific for minor H antigens.

PMID- 1353917
TI  - 2nd Congress of the Asian Transplantation Society. Proceedings. Taipei, Taiwan,
      November 26-28, 1991.

PMID- 1353916
TI  - T cell receptor V beta gene usage in HLA-DR1-reactive human T cell populations.
      The predominance of V beta 8.
AB  - The functional specificity and T cell receptor (TCR) V beta gene expression of
      three class II HLA-DR1-reactive human T cell populations were examined. WP2, a
      renal allograft-derived, long-term CD4+ T cell line, was specifically cytotoxic
      for DR1, one of the mismatched antigens present on the allograft. Initial studies
      of WP2 using six TCR V beta-specific mAb revealed a predominance of T cells
      expressing a member of the V beta 8 gene family. A smaller, yet significant,
      number of cells expressed TCR using V beta 5.1. Semiquantitative V beta-specific
      polymerase chain reaction (PCR) analyses of RNA derived from this T cell line
      confirmed the presence of V beta 8 and V beta 5.1 messages. The PCR signal for V
      beta 8 was the strongest, followed by those for V beta 4 and V beta 5. An earlier
      WP2 culture had a very similar PCR profile, with a dominant signal for V beta 8,
      although signals for V beta 4 and V beta 5 were considerably lower. Previous PCR
      analyses of eight other renal allograft-derived, long-term T cell lines, grown
      under identical in vitro conditions, revealed no other example of predominant
      usage of V beta 8. We established two replicate long-term, anti-DR1 mixed
      lymphocyte reactions using PBL from two unrelated normal donors as responder and
      stimulator. The MLR were given alloantigen every 10 days, and RNA was obtained
      from the cultured cells immediately prior to each stimulation. PCR analyses of
      RNA taken at 10-day intervals over a total of 60-70 days indicated that, although
      the MLR were initially quite heterogeneous with regard to V beta message
      expression, by the end of the fourth or fifth Ag cycle the predominant PCR
      signals observed in both MLR were for V beta 8. These results suggest that T
      cells using V beta 8 gene-encoded segments as part of their TCR may have a
      selective advantage in responses to DR1.

PMID- 1353918
TI  - Expression of intercellular adhesion molecule-1 and perforin on kidney allograft
      rejection.

PMID- 1353919
TI  - Expression of ICAM-1 and HLA-DR antigens by tubular cells and immune cell
      infiltration in human renal allografts.

PMID- 1353920
TI  - Cadaveric renal transplantation and HLA-DPB1 genotype compatibility.

PMID- 1353921
TI  - Sequential measurements of urine GP-DAP as a new indicator of renal allograft
      rejection.

PMID- 1353922
TI  - The expression of LFA-1/ICAM-1 in liver transplantation in rats.

PMID- 1353924
TI  - 10 years of cyclosporine in clinical practice. Past, present, and future research
      in transplantation immunology. Symposium proceedings. Basel, Switzerland,
      November 11-12, 1991.

PMID- 1353923
TI  - Histologic and immunohistochemical evaluation of deoxyspergualin-treated rat
      renal transplants.

PMID- 1353925
TI  - Scope and design of the GUSI international research program.
AB  - During the 1980s a large new simulated underwater saturation diving system was
      constructed at GKSS, Geesthacht, Germany. This German Underwater Simulator (GUSI)
      has performed over 18 trimix (helium, 5% nitrogen, oxygen) dives with 115 divers
      at depths to 600 m, including 9 to 450 m or deeper for a total of 2672 man-days
      of saturation and 994 days of welding and other work. From October 1989, an
      international research program was initiated to permit scientists from other
      countries to carry out physiologic and medical research during these working
      dives. The results of the first year's program from 3 dives, GUSI 14, 16, and 17,
      all to 450 m, are described in this special edition of Undersea Biomedical
      Research. This brief paper gives the scope, design, and objectives of the
      program, the dive profiles, and the scientists and projects involved.

PMID- 1353926
TI  - Effect of mental task load on fronto-central theta activity in a deep saturation
      dive to 450 msw.
AB  - The increase of theta activity (4-7 Hz) in the electroencephalogram (EEG) during
      deep diving is commonly attributed to pathophysiologic mechanisms underlying the
      high pressure neurologic syndrome. The aim of this study was to clarify whether
      more precise cognitive aspects of the condition may be described in which theta
      activity occurs during a deep dive. Among 4 divers who were repeatedly examined
      during the GUSI 14 dive to 450 msw, 3 divers exhibited a pronounced correlation
      between short-term memory load, as varied by the memory set size of Sternberg's
      memory search task (MST), and the size of a distinct peak in the theta band of
      the EEG-power spectrum. The power of this peak was greatest in the fronto-central
      electrode position (Fz), increased dramatically during MST-performance at
      pressure, and failed to subside fully 1 day before surfacing. Despite the close
      dependency of observed theta activity on cognitive demands, no consistent
      correlation with performance measures (mean reaction time and errors) was found.
      In one diver, theta waves of similar morphology appeared in the resting EEG and
      increased significantly during the dive. We suggest two alternative explanations
      for the positive interaction of memory load and hyperbaric exposure on Fz-theta:
      a) Both factors induce a state of increased mental effort or selectivity of
      attention, known to be accompanied by frontal theta activity from normobaric
      studies. b) Pressure abnormally facilitates or patterns rhythmical excitations
      underlying theta activity that would occur naturally to a lesser extent during
      certain mental activities, learning, or repetitive short-term memory operations.

PMID- 1353927
TI  - Evaluation of energy requirements from body mass, lean body mass, fat content,
      and energy intake in GUSI dives.
AB  - This study reports the changes in body composition measured during 6 deep
      saturation dives, the depths and the working hours performed during the dives,
      and the effects of these parameters on the energy requirements. Changes in lean
      body mass could be avoided if the working days amounted to 40-45% of the total
      dive time. Energy requirement depended not only on working days but also on the
      diving depth. Physical work at great depth requires a disproportional increase in
      the energy requirements beginning between 200 and 360 m. Under working conditions
      at 450 msw, energy requirements increased about 30% relative to the total energy
      needs under normal conditions.

PMID- 1353928
TI  - An investigation of cardiovascular reflexes during a trimix saturation dive to
      450 msw (GUSI 17).
AB  - The study examines the hypothesis that the carotid sinus heart rate baroreflex
      responses are changed in human subjects on exposure to 450 msw. Baroreceptor
      reflex changes in heart rate (expressed as ms/mmHg applied pressure) were evoked
      by application of negative or positive pressure to a cuff surrounding the neck.
      At 450 msw using trimix, the mean resting heart rate of divers slowed
      significantly from 64 +/- 1.3 beats/min at surface to 55 +/- 1.4 beats/min at 450
      msw, respiratory rate decreased from 15 +/- 1.4 at surface to 11 +/- 2 at 450
      msw, and sinus arrhythmia increased. There was no change in arterial blood
      pressure. Baroreceptor reflex sensitivity to an increased carotid sinus
      transmural pressure was reduced from 5.6 +/- 2.9 (mean +/- SEM) at surface to 2.4
      +/- 0.8 ms.mmHg-1 at 450 msw; sensitivity to decreased carotid sinus transmural
      pressure increased from 2.2 +/- 0.4 ms.mmHg-1 at surface to 5.1 +/- 0.2 ms.mmHg-1
      at 450 msw. A progressive shortening of cardiac interval during breath hold in
      expiration was also noted. When this shortening of interval was incorporated into
      the analysis of baroreceptor reflex sensitivity, no significant change in
      sensitivity was observed but the overall baroreflex stimulus-response
      relationship shifted downward.

PMID- 1353929
TI  - Urinary vasopressin and aldosterone and plasma volume during a saturation dive to
      450 m.
AB  - Urinary vasopressin (VP), aldosterone (ALDO), osmotic substances, sodium
      excretion, and plasma volume were assessed in 4 healthy male divers during 2
      predive control days, 2 compression days, 6 days at 46 atm abs, and 26 days of
      decompression with stops at 37 and 27 atm abs. At pressure the ambient gas was
      trimix (0.5 atm abs O2:5% N2:remainder He). All urine was collected throughout
      the dive. Samples were divided into daytime (0700-1900) and nighttime (1900
      0700). Indocyanine green dye dilution was used to determine plasma volume at
      predive 1, 46, and 24 atm abs. In agreement with previous dives at 31 atm abs,
      there was a decrease in VP excretion during compression lasting until return to 1
      atm abs (P less than 0.05). Also similar to the shallower dives at 31 atm abs,
      the normal diurnal pattern of VP excretion, daytime higher than nighttime (P less
      than 0.05), disappeared at pressure. Urine osmolality showed alterations
      compatible with responses to VP. In contrast to previous studies at 31 atm abs,
      but in agreement with a previous study at 49.5 atm abs, there was no sustained
      increase in urinary ALDO excretion and only a transient natriuresis during the
      compression phase, followed by a reduced sodium excretion. In confirmation of
      earlier conclusions from indirect evidence, direct measurements of plasma volume
      indicated a reduction of about 20% (P less than 0.05) at 46 atm abs which
      remained reduced after decompression to 24 atm abs.

PMID- 1353930
TI  - The metabolism of piperidine-type phenothiazine antipsychotic agents. I.
      Sulforidazine in the rat.
AB  - 1. The metabolism of the piperidine-type, phenothiazine antipsychotic agent,
      sulforidazine, was studied in female rats after a 20 mg/kg single oral dose. 2.
      Compounds identified in urine were sulforidazine, sulforidazine ring sulphoxide,
      the lactam of sulforidazine, the lactam of sulforidazine ring sulphoxide, two
      diastereomers of N-desmethylsulforidazine ring sulphoxide and a phenolic
      derivative of sulforidazine. 3. Metabolites were separated by h.p.l.c. prior to
      mass spectrometric or g.l.c.-mass spectrometric analysis. Except in the case of
      the phenolic metabolite, structures were confirmed by direct comparison of
      electron impact mass spectra and chromatographic behaviour with those of
      authentic samples. To facilitate identification of the phenolic metabolite the
      crude urinary extract was treated with a silylating reagent and analysed by
      h.p.l.c.-mass spectrometry with a plasmaspray interface. 4. Despite the
      availability of authentic standards of sulforidazine N-oxide and sulforidazine
      N,S-dioxide neither of these compounds could be identified in urinary extracts
      obtained from rats. 5. Sulforidazine underwent extensive metabolism in rats as
      only 2.3 +/- 0.4% (n = 5) of the dose was present as unchanged sulforidazine in
      24 h urine. The lactam of sulforidazine (0.1 +/- 0.1%) was a minor metabolite
      whereas the lactam of sulforidazine ring sulphoxide was 3.2 +/- 2.6% dose. 6.
      Sulforidazine sulphoxide (12.1 +/- 1.6%) was a major metabolite and its
      diastereomers were present in similar amounts.

PMID- 1353931
TI  - [Drug dependence in therapy of chronic pain].
AB  - The use of drugs in pain therapy is characterized by the fear of addiction. As a
      result strong analgesics are underused. To compensate the missing analgesic
      effect the additional use of psychotropic drugs is common. There is still little
      knowledge that just this therapeutic strategy of underuse leads to iatrogenic
      addiction. To avoid misunderstandings and irritations in the discussion around
      addiction, there must be clearly distinguished between physical and psychological
      dependence. There is sufficient evidence that especially tranquilizers and mixed
      analgesics induce the development of psychological dependence. In pain therapy
      there is no indication for these substances. In contrast opioids can be used
      without causing psychological dependence, presuming the guidelines of drug
      therapy in chronic pain (e.g. WHO guidelines) are attended.

PMID- 1353932
TI  - [Antihypertensive therapy and modification of metabolic risk factors (glucose and
      lipid metabolism)].
AB  - Meta-analysis of several large interventional trials in patients with mild to
      moderate hypertension has shown that coronary events are reduced to a much lesser
      extent than expected. One of the possible explanations for this are the metabolic
      side-effects of diuretics and betablockers used in these trials that may
      counteract their beneficial blood-pressure-lowering effect. Diuretics, especially
      thiazide, increase total cholesterol (+5%) and LDL-cholesterol (+10%), while
      betablockers decrease HDL-cholesterol (-5%) and increase triglycerides (+20%).
      Calcium antagonists and ACE-inhibitors do not affect lipids, and alpha-blockers
      have some beneficial effects. Regarding the carbohydrate metabolism, diuretics
      and betablockers decrease insulin sensitivity, increase plasma insulin, LDL
      cholesterol, and triglycerides, and reduce HDL-cholesterol. Calcium channel
      blockers are neutral, while alpha-blockers and ACE-inhibitors improve glucose
      tolerance and reduce insulin resistance. To date, the clinical relevance of this
      side-effects is not known. Controlled, long-term trials in hypertensive patients
      with calcium channel blockers, ACE-inhibitors, and alpha-blockers are needed.

PMID- 1353933
TI  - [Duration of the effect and dose-response relationship of ridazolol in patients
      with coronary heart disease].
AB  - The dose-effect relation and duration of action of 10 mg, 20 mg, 40 mg, and 80 mg
      ridazolol on ischemic ST-segment depression in exercise-ECG were determined in a
      randomized, double-blind, acute, cross-over study of 15 patients with confirmed
      coronary artery disease and reproducible ST-segment depression. Maximal reduction
      of ST-segment depression in comparison to placebo during constant exercise was
      0.16 vs. 0.25 mm (n.s.) after 10 mg, 0.09 vs. 0.25 mm (p less than 0.01) after 20
      mg, 0.11 vs. 0.25 mm (p less than 0.01) after 40 mg, and 0.07 vs. 0.25 mm (p less
      than 0.01) after 80 mg ridazolol. A remarkable reduction of ST-segment depression
      under placebo was seen in the third and fifth hours after application. Systolic
      blood pressure under exercise was reduced significantly after 80 mg ridazolol
      (145 vs. 176 mm Hg; (p less than 0.05) over a period of 5 h. Heart-rate was
      reduced significantly after 80 mg ridazolol (102 vs. 131/min; p less than 0.05)
      for 5 h. Rate-pressure product after 20 mg (174 vs. 234 mm Hg/min; p less than
      0.01), 40 mg (169 vs. 234 mm Hg/min; p less than 0.01), and 80 mg (153 vs. 234 mm
      Hg/min; p less than 0.01) ridazolol was reduced significantly over 3 to 5 h. 20,
      40 and 80 mg ridazolol show a good antianginal and antihypertensive efficacy.
      Blood pressure and heart-rate under exercise were significantly reduced over 5 h.
      In contrast, improvement of ST-segment depression only lasted 1 h. Ridazolol was
      well tolerated.

PMID- 1353934
TI  - [The antidystrophic effect of the action of beta-adrenoblockaders in local damage
      to the nervous system].
AB  - It has been established that the lesion of the sciatic nerve, accompanied by a
      disturbance of normal neurotrophic provision of a kidney as a result of coming to
      the organ of the perverted nervous stimuli (by the neuro-conductive path through
      sympathetic nerves and by participation of the hypothalamus--hypophysis-
      peripheral glands system), leads to disturbance of functioning of mineral
      corticoid receptors of kidneys. It has been also established that simultaneous
      pharmacological blockade of neuro-conductive and humoral pathways of transmission
      to the kidney of pathological stimuli from the central stump of the cut sciatic
      nerve prevents the development of trophic organ disturbances, tested by the state
      of the kidney mineral-corticoid receptor apparatus, while pharmacological
      stimulation of sympathetic nervous system leads to the greater disturbance of
      aldosterone reception by the cells of kidney channels. A valid conclusion can be
      made that propranolol is a substance, which may weaken possible non-adequate
      reactions of peripheral tissues to the action of physiologically active
      substances during the development of the consequences of the lesion of the
      nervous system and thus to prevent the development of neurogenic dystrophies.

PMID- 1353936
TI  - Advances in enzyme regulation. Proceedings of the 32nd Symposium on Regulation of
      Enzyme Activity and Synthesis in Normal and Neoplastic Tissues. Indianapolis,
      Indiana, September 30-October 1, 1991.

PMID- 1353937
TI  - Soluble guanylate cyclase of platelets: function and regulation in normal and
      pathological states.
AB  - Chromatography of 105,000 x g supernatants of human and rat platelets on DEAE
      cellulose yielded identical elution profiles containing 2 protein fractions
      (peaks I and II). Only peak II was found to possess guanylate cyclase activity.
      In the spectrum of the 105,000 x g supernatant of human platelets the absorption
      maximum was specified at 410 nm (the Soret band) which disappeared from the
      spectrum of the active protein fraction (peak II) but was detected in the
      nonactive fraction (peak I). The enzyme preparation was obtained in the heme
      deficient form. In the experiments with rat platelets, the Soret band was absent
      from the corresponding spectra and the enzyme was not activated by sodium
      nitroprusside; i.e., in soluble guanylate cyclase of rat platelets, unlike the
      generally accepted notion, the heme is not a prosthetic group of the enzyme. It
      was shown that carnosine (beta-alanyl-L-histidine), a water-soluble antioxidant,
      inhibits guanylate cyclase activation by sodium nitroprusside. This inhibitory
      effect is caused by the interaction of carnosine with the guanylate cyclase heme
      and can be used for evaluating the degree of saturation of the enzyme with the
      heme. ADP-induced aggregation of human platelets (donors) is accompanied by a
      fall in the basal guanylate cyclase activity (with Mg2+) and the enhancement of
      the enzyme stimulation with sodium nitroprusside, protoporphyrin IX, arachidonic
      acid and L-arginine with simultaneous cGMP elevation in platelets. A hypothetic
      scheme of the regulatory role of cGMP in platelet aggregation is proposed. In the
      experiments with the acute myocardial ischemia of rats, 15 min after the surgery
      a sharp fall in the platelet guanylate cyclase activity accompanied by a decrease
      in the enzyme activity in the ischemic zone of the left ventricle of heart took
      place. The results provided evidence of the high sensitivity of platelet
      guanylate cyclase to pathological changes occurring in the myocardium at the
      earliest stages of the development of pathology.

PMID- 1353935
TI  - [The effect of dopamine receptor stimulation on the motor and stereotypic
      activities of mice with different genotypes].
AB  - On mice of 8 highly inbred strains--BALB/c, DBA/2, C57B1/6, CBA, DD, CC57Br,
      C3H/He, A/He--the role was studied of dopamine receptors of the first and second
      types (D1 and D2) in the regulation of the general motor activity and stereotypic
      climbing. Significant dependence was shown of these types of dopamine-dependent
      behaviour on the genotype. Agonist of D1/D2 receptors, apomorphine decreased the
      motor activity of animals of the all studied strains, and this effect
      significantly depended on the genotype. The inhibition of locomotion after
      selective stimulation of D2 receptors (by LY 171555) was significant.
      Distribution of mouse strains according to expressiveness of climbing after
      administration of apomorphine differed from their distribution by the level of
      motor activity. Selective stimulation of D1 receptors, on the whole, elicited
      climbing of lesser intensity than D1/D2 activation (excluding CBA strain), and
      administration of D2 agonist did not induce it at all. Probably, for full
      expression of behavioural reactions the interaction between D1 and D2 receptors
      is required.

PMID- 1353938
TI  - Regulation of GTP biosynthesis.
AB  - In the regulation of GTP biosynthesis, complex interactions are observed. A major
      factor is the behavior of the activity of IMPDH, the rate-limiting enzyme of de
      novo GTP biosynthesis, and the activity of GPRT, the salvage enzyme of guanylate
      production. The activities of GMP synthase, GMP kinase and nucleoside-diphosphate
      kinase are also relevant. In neoplastic transformation, the activities and
      amounts of all these biosynthetic enzymes are elevated as shown by kinetic assays
      and by immunotitration for IMPDH. In cancer cells, the up-regulation of guanylate
      biosynthesis is amplified by the concurrent decrease in activities of the
      catabolic enzymes, nucleotidase, nucleoside phosphorylase, and the rate-limiting
      purine catabolic enzyme, xanthine oxidase. The up-regulation of the capacity for
      GTP biosynthesis is also manifested in the stepped-up capacity of the overall
      pathways of de novo and salvage guanylate production. The linking with neoplasia
      is also seen in the elevation of the activities of IMPDH and GMP synthase and de
      novo and salvage pathways as the proliferative program is expressed as cancer
      cells enter log phase in tissue culture. The activity of GMP reductase showed no
      linkage with neoplastic or normal cell proliferation; however, in induced
      differentiation in HL-60 cells the activity increased concurrently with the
      decline in the activity of IMPDH. This reciprocal regulation of the two enzymes
      is observed in differentiation induced by retinoic acid, DMSO or TPA in HL-60
      cells. In support of enzyme-pattern-targeted chemotherapy, evidence was provided
      for synergistic chemotherapy with tiazofurin (inhibitor of IMPDH) and
      hypoxanthine (competitive inhibitor of GPRT and guanine salvage activity) in
      patients and in tissue culture cell lines. These investigations should contribute
      to the clarification of the controlling factors of GMP biosynthesis, the role of
      the various enzymes, the behavior of GMP reductase in mammalian cells and the
      application of the approaches of enzyme-pattern-targeted chemotherapy in
      patients.

PMID- 1353939
TI  - Genetic analysis of 24 French families with multiple endocrine neoplasia type 2A.
AB  - The gene for multiple endocrine neoplasia type 2A (MEN2A) has been mapped to the
      pericentromeric region of chromosome 10 by linkage analysis. Thirty-four families
      with multiple cases of medullary carcinoma of the thyroid (MTC), including 24
      families with origins in France, have been typed with nine polymorphic markers
      spanning the centromere of chromosome 10. No recombination was observed between
      the MEN2A locus and either of the four loci D10Z1 (lod score 12.79), D10S102 (lod
      score 6.38), D10S94 (lod score 7.76), and D10S34 (lod score 5.94). There was no
      evidence for genetic linkage heterogeneity in the panel of 34 families.
      Haplotypes were constructed for a total of 11 polymorphisms in the MEN2A region,
      for mutation-bearing chromosomes in 24 French families and for 100 spouse
      controls. One haplotype was present in four MEN2A families but was not observed
      in any control (P less than .01). Two additional families share a core segment of
      this haplotype near the MEN2A gene. It is likely that these six families have a
      common affected ancestor. Because the incidence of pheochromocytoma among
      carriers varies from 0% to 74% within these six families, it is probable that
      additional factors modify the expression of the MEN2A gene.

PMID- 1353942
TI  - The Effects of Cigarette Smoking: A Global Perspective. Symposium proceedings.
      Washington, D.C., July 1991.

PMID- 1353940
TI  - Osteogenesis imperfecta type I is commonly due to a COL1A1 null allele of type I
      collagen.
AB  - Dermal fibroblasts from most individuals with osteogenesis imperfecta (OI) type I
      produce about half the normal amount of type I procollagen, as a result of
      decreased synthesis of one of its constituent chains, pro alpha 1 (I). To test
      the hypothesis that decreased synthesis of pro alpha (I) chains results from
      mutations in the COL1A1 gene, we used primer extension with nucleotide-specific
      chain termination to measure the contribution of individual COL1A1 alleles to the
      mRNA pool in fibroblasts from affected individuals. A polymorphic MnlI
      restriction endonuclease site in the 3'-untranslated region of COL1A1 was used to
      distinguish the transcripts of the two alleles in heterozygous individuals.
      Twenty-three individuals from 21 unrelated families were studied. In each case
      there was marked diminution in steady-state mRNA levels from one COL1A1 allele.
      Loss of an allele through deletion or rearrangement was not the cause of the
      diminished COL1A1 mRNA levels. Primer extension with nucleotide-specific chain
      termination allows identification of the mutant COL1A1 allele in cell strains
      that are heterozygous for an expressed polymorphism. It is applicable to sporadic
      cases, to small families, and to large families in whom key individuals are
      uninformative at the polymorphic sites used in linkage analysis, making it a
      useful adjunct to the biochemical screening of collagenous proteins for OI.

PMID- 1353941
TI  - Associations between mutations and a VNTR in the human phenylalanine hydroxylase
      gene.
AB  - The HindIII RFLP in the human phenylalanine hydroxylase (PAH) gene is caused by
      the presence of an AT-rich (70%) minisatellite region. This region contains
      various multiple of 30-bp tandem repeats and is located 3 kb downstream of the
      final exon of the gene. PCR-mediated amplification of this region from haplotyped
      PAH chromosomes indicates that the previously reported 4.0-kb HindIII allele
      contains three of these repeats, while the 4.4-kb HindIII allele contains 12 of
      these repeats. The 4.2-kb HindIII fragment can contain six, seven, eight, or nine
      copies of this repeat. These variations permit more detailed analysis of mutant
      haplotypes 1, 5, 6, and, possibly, others. Kindred analysis in phenylketonuria
      families demonstrates Mendelian segregation of these VNTR alleles, as well as
      associations between these alleles and certain PAH mutations. The R261Q mutation,
      associated with haplotype 1, is associated almost exclusively with an allele
      containing eight repeats; the R408W mutation, when occurring on a haplotype 1
      background, may also be associated with the eight-repeat VNTR allele. Other PAH
      mutations associated with haplotype 1, R252W and P281L, do not appear to
      segregate with specific VNTR alleles. The IVS-10 mutation, when associated with
      haplotype 6, is associated exclusively with an allele containing seven repeats.
      The combined use of this VNTR system and the existing RFLP haplotype system will
      increase the performance of prenatal diagnostic tests based on haplotype
      analysis. In addition, this VNTR may prove useful in studies concerning the
      origins and distributions of PAH mutations in different human populations.

PMID- 1353943
TI  - Nicotine and the central nervous system: biobehavioral effects of cigarette
      smoking.
AB  - The effects of nicotine, like those of other drugs with potential for abuse and
      dependence, are centrally mediated. The impact of nicotine on the central nervous
      system is neuroregulatory in nature, affecting biochemical and physiological
      functions in a manner that reinforces drug-taking behavior. Dose-dependent
      neurotransmitter and neuroendocrine effects occur as plasma nicotine levels rise
      when a cigarette is smoked. Circulating levels of norepinephrine and epinephrine
      increase, and the bioavailability of dopamine is altered as well. Among the
      neuroendocrine effects are release of arginine vasopressin, beta-endorphin,
      adrenocorticotropic hormone, and cortisol. Notably, several of these
      neurochemicals are psychoactive and/or known to modulate behavior. Thus,
      affective states or cognitive demands may be favorably modified (at least
      temporarily) by nicotine intake. When nicotine is inhaled, the neuroregulatory
      effects just described are immediately available and the reinforcing effects of
      the drug are maximized. On the other hand, nicotine gum and most other nicotine
      replacement vehicles in current use have a slower onset of action, resulting in
      less reinforcement value. Recent data suggest that smoking cessation rates may be
      optimized by tailoring the dose of nicotine replacement (for example, 2 or 5 mg
      of nicotine gum) to the individual degree of nicotine dependence. In view of the
      dynamic interactions between the neuroregulatory effects of nicotine and a host
      of environmental conditions, nicotine replacement therapy is best carried out in
      combination with behavior modification techniques.

PMID- 1353944
TI  - Sinusitis in HIV-1 infection.
AB  - PURPOSE: To determine the clinical and radiographic characteristics of sinusitis
      in patients with human immunodeficiency virus type 1 (HIV-1) infection. PATIENTS
      AND METHODS: A retrospective study was performed that identified all HIV-1
      infected patients with sinus radiographs, sinus computed tomograms, or magnetic
      resonance imaging of the head between 1982 and 1989 (n = 145). Medical record
      review detailed the clinical course and laboratory parameters in all patients.
      RESULTS: Eighty-nine patients had radiographic evidence of sinusitis; 75 patients
      had adequate clinical data and comprise the study group. Acute sinusitis was seen
      in 10 patients (13%), while all 75 patients had mucosal thickening indicative of
      chronic sinusitis. Fifty patients (67%) were symptomatic with fever, nasal
      congestion or discharge, and headache being the most common symptoms; nineteen
      patients (25%) were asymptomatic when their radiographs showed active disease.
      The mean CD4 count for the group was 276 cells/mm3; 32 (43%) had CD4 counts less
      than or equal to 100 cells/mm3. Twenty-three patients (31%) received antibiotics
      orally, parenterally, or both. CONCLUSIONS: Sinusitis appears to occur frequently
      in HIV-infected patients, is often asymptomatic, may be recurrent or refractory,
      and may be associated with declining immunocompetence in HIV-infected patients.

PMID- 1353945
TI  - The primary structure of the prion protein influences the distribution of
      abnormal prion protein in the central nervous system.
AB  - We immunohistochemically examined tissue sections from patients with prion
      protein (PrP) polymorphism using hydrolytic autoclaving enhancement. Abnormal PrP
      accumulations could be classified into plaque formations (plaque-type) and the
      diffuse gray matter stainings including synaptic structures (synaptic-type).
      Insertional polymorphism, a point mutation in codon 102 or 117/129, and a
      polymorphism in codon 129 (Val129) result in plaque-type PrP accumulations. The
      patients with codon 102 mutation also have synaptic-type PrP accumulations.
      However, a point mutation in codon 200 did not show plaque-type accumulations,
      and only showed synaptic-type PrP accumulations. Likewise, sporadic Creutzfeldt
      Jakob disease patients without any known mutations only have synaptic type
      accumulations. These results imply that the primary structures of PrP influence
      the phenotype of prion diseases, especially in abnormal PrP distributions of the
      central nervous system.

PMID- 1353947
TI  - Towards a definition of transnationalism. Introductory remarks and research
      questions.

PMID- 1353948
TI  - Psychophysiology and Experimental Psychopathology. A tribute to Samuel Sutton.
      New York, New York, March 18, 1987.

PMID- 1353946
TI  - Malignant fibrous histiocytoma. Proliferative compartment and heterogeneity of
      "histiocytic" cells.
AB  - To elucidate the precise origin and characteristics of the proliferating cells in
      malignant fibrous histiocytoma (MFH), the authors analyzed 33 MFH tumors, using
      immunohistochemical techniques with a panel of 12 antibodies. All three types of
      MFH cells (spindle cells, polygonal cells, and bizarre giant cells) stained
      positively for mesenchymal antigens (FU3 and vimentin) but did not stain for
      macrophage/histiocyte markers (HAM 56 and CD68). Therefore, the MFH cells may not
      represent true histiocytes, although they may be mesenchymal-derived cells
      behaving as "facultative histiocytes" with superficial resemblance to actual
      histiocytes. Normal histiocytes in the stroma tested positive for
      macrophage/histiocyte antigens; the most common cells were HAM 56-positive cells
      constituting 30-80% of nonneoplastic stromal cells, followed by those positive
      for CD68 (10-50%), Mac 387 (less than 2%), and S-100 protein (less than 1%). Our
      results indicate the presence of heterogeneity of "histiocytic" cells in MFH.
      Proliferating-cell nuclear antigen (PCNA) was expressed not only in the spindle
      and polygonal MFH cells but also in the bizarre giant cells. These findings
      suggest that all three types of MFH cells participate in the proliferative
      compartment of MFH. Uneven PCNA staining of the irregular nuclear segments of the
      bizarre giant cells may result in abnormal DNA synthesis, possibly contributing
      to the marked diversity of nuclear morphology in MFH. Touton-type and osteoclast
      like giant cells did not stain for PCNA but stained positively for histiocytic
      markers. Therefore, these giant cells may lack proliferative activity and
      probably result from normal histiocytes fusing together.

PMID- 1353949
TI  - P3 and schizophrenia.

PMID- 1353950
TI  - Biochemistry of peroxisomes.

PMID- 1353951
TI  - The biochemistry of 3'-end cleavage and polyadenylation of messenger RNA
      precursors.

PMID- 1353952
TI  - Bacteriophage phi 105clz induces the GroEL-homologue protein in Bacillus
      subtilis.
AB  - Using two-dimensional polyacrylamide gel electrophoresis, the GroEL homologue of
      Bacillus subtilis was shown to be induced upon infection with phi 105clz, a clear
      plaque mutant of the temperate bacteriophage phi 105. Western blotting of one
      dimensional polyacrylamide gels also showed the induction of the GroEL homologue
      when cells were infected with phi 105clz.

PMID- 1353954
TI  - College of American Pathologists Conference XXI, Validation of Clinical
      Laboratory Methods and Instruments. October 21-23, 1991.

PMID- 1353953
TI  - Clinical and laboratory correlates of human immunodeficiency virus infection in a
      cohort of intravenous drug users from New York, NY.
AB  - BACKGROUND: The human immunodeficiency virus (HIV) epidemic has increasingly
      involved intravenous drug users. Few studies have attempted to define its
      clinical and laboratory characteristics in this population. METHODS: We recruited
      223 intravenous drug users from New York, NY, for a prospective study of the
      natural course of HIV infection. Medical history, physical examination, medical
      staging, and immunologic assessments were performed at 6-month intervals. We
      examined the baseline findings among this cohort. RESULTS: Of the total cohort,
      65.9% were men and 34.1% were women, with 70.9% African American, 12.6% white,
      11.7% white Latino, and 4.9% black Latino. At baseline, 44.4% were HIV negative
      and 55.6% were HIV positive. No significant association was noted between
      ethnicity, gender, and serologic status. Also no significant difference was noted
      for homelessness either across serologic status or gender. There was a trend
      toward an association between gender and use of drugs during the week before
      interview; the women showed higher drug use. A significant association was noted
      between HIV serologic status and reported history of pneumonia, oral candidiasis,
      cough, night sweats, fever, and lymphadenopathy on physical examination. In a
      regression model, white blood cell count, hematocrit, symptom/sign complex score,
      and CD4 cell number were significantly associated with HIV status. CONCLUSION:
      This study provided important historical, clinical, and immunologic
      characteristics that are useful in the identification and evaluation of the HIV
      infected intravenous drug user.

PMID- 1353955
TI  - Receptor systems in the non-failing human heart.
AB  - Catecholamines acting through beta 1- and beta 2-adrenoceptors cause positive
      inotropic and chronotropic effects in the human heart. In recent years, however,
      evidence has accumulated that in the human heart also other receptor systems can
      affect heart rate and/or contractility. Positive inotropic effects can be
      mediated by receptor systems acting through accumulation of intracellular cAMP
      (Gs-protein coupled receptors such as 5-HT4-like, histamine H2, and vasoactive
      intestinal peptide) or by receptor systems acting independent of cAMP possibly
      through the phospholipase C/diacylglycerol/inositol-1,4,5-trisphosphate pathway
      (such as alpha 1-adrenergic, angiotensin II, and endothelin). In the non-failing
      human heart, however, activation of all these receptor systems induces only
      submaximal positive inotropic effects when compared with those caused by beta
      adrenoceptor stimulation, indicating that in humans the cardiac beta-adrenoceptor
      Gs-protein-adenylate cyclase pathway is the most powerful mechanism to increase
      heart rate and contractility. On the other hand, at least three receptor systems
      acting through inhibition of cAMP formation (Gi-protein coupled receptors) exist
      in the human heart: muscarinic M2-, adenosine A1-, and somatostatin-receptors.
      Activation of M2- and A1-receptors causes negative inotropic effects in the non
      failing human heart: in atria activation of both receptors causes decreases in
      basal as well as in isoprenaline-stimulated force of contraction, but in
      ventricles only isoprenaline-stimulated force of contraction is depressed.

PMID- 1353956
TI  - Cellular and molecular alterations in the failing human heart. Symposium.
      Gargellen, Montafon, Austria, June 1991.

PMID- 1353957
TI  - Nutrition and Cardiovascular Risks. 29th Symposium of the Group of European
      Nutritionists. Balatonfoldvar, Hungary, April 24-26, 1991.

PMID- 1353959
TI  - Interaction of P-glycoprotein with a hydrophobic component of rat urine.
AB  - The presence of an endogenous P-glycoprotein substrate in rat urine was examined
      by testing the ability of a hydrophobic extract to reverse multidrug resistance
      in CHO cells and to inhibit [3H]azidopine photolabelling. The accumulation of
      several hydrophobic drugs and dyes, known to be transported by P-glycoprotein,
      was dramatically enhanced in multidrug-resistant CHO cells (CHRC5) by a component
      contained in a hydrophobic extract prepared from rat urine by octadecyl (C18)
      reverse phase chromatography. The biological action of this urinary component
      involves a direct interaction with P-glycoprotein since it blocked photolabelling
      of the protein with [3H]azidopine. The effective concentration of the substance
      required to enhance drug accumulation and inhibit photolabelling was similar and
      within the range of its urinary content. These results suggest that a hydrophobic
      substance in urine may be an endogenous substrate of kidney P-glycoprotein.

PMID- 1353958
TI  - Sequence of the complete cDNA and the 5' structure of the human sucrase
      isomaltase gene. Possible homology with a yeast glucoamylase.
AB  - The complete sequence of the 6 kb cDNA and the 5' genomic structure are reported
      for the gene coding for the human intestinal brush border hydrolase sucrase
      isomaltase. The human sucrase-isomaltase cDNA shows a high level of identity
      (83%) with that of the rabbit enzyme, indicating that the protein shares the same
      structural domains in both species. In addition to the previously reported
      homology with lysosomal alpha-glucosidase, the sucrase and isomaltase subunits
      also appear to be homologous to a yeast glucoamylase. A 14 kb human genomic clone
      has been isolated which includes the first three exons and the first two introns
      of the gene, as well as 9.5 kb 5' to the major start site of transcription. The
      first exon comprises 62 bp of untranslated sequence and the second starts exactly
      at the initiation ATG codon. Typical CAAT and TATA boxes are seen upstream of the
      first exon. A genetic polymorphism is described which involves a PstI site in the
      second intron. Southern blotting, sequencing and mRNA studies indicate that the
      structures of the sucrase-isomaltase gene and its mRNA are unaltered in the two
      human colon cancer cell lines Caco-2 and HT-29 in comparison with normal human
      small intestine.

PMID- 1353961
TI  - Total prevention of the development of in vitro tolerance to organic nitrates.
      Experiments with antioxidants.
AB  - The nearly total inhibition of development of pharmacological tolerance to an
      organic nitrate is reported here for the first time. The development of in vitro
      tolerance in the rabbit aorta to isosorbide-5-mononitrate (CAS 87-33-2) was
      potently inhibited by five structurally unrelated antioxidants--diaminodurol,
      ascorbic acid, potassium sulphite, pyrogallol and quercetin. Diaminodurol,
      ascorbic acid and potassium sulphite decreased, but quercetin increased, the
      spasmolytic activity of isosorbide-5-mononitrate. Diaminodurol, potassium
      sulphite, quercetin and ascorbic acid potently inhibited the spasmolytic activity
      of nitric oxide (NO). Quercetin also inhibited the development of in vitro
      tolerance to glyceryl trinitrate. It is suggested that tolerance to organic
      nitrates is the result of biochemical damage caused by a reactive intermediate
      such as NO. To test this possibility directly the effect of pretreatment with NO
      on the spasmolytic activity of glyceryl trinitrate (CAS 55-63-0) was examined.
      This pretreatment produced a small but significant tolerance to glyceryl
      trinitrate and to SIN-1 (3-morpholinosydnone imine), which also acts through
      guanylate cyclase. There was no effect on the activity of the unrelated
      vasodilators nitrendipine and theophylline. It is concluded that the reaction
      between NO and soluble quanylate cyclase is a real but minor cause of tolerance
      to organic nitrates. Other possible mechanisms of tolerance development are
      discussed.

PMID- 1353962
TI  - Inhibition of human phospholipase C by aurothiomalate and (triethylphosphine)
      gold complexes.
AB  - The effect of several gold complexes on the activity of phospholipase C from
      human blood platelets was studied in vitro. Aurothiomalate and auranofin--2
      agents used for the chrysotherapy of rheumatoid arthritis--, gold chloride,
      (triethylphosphine)gold chloride, and 5 newly synthesized (triethylphosphine)gold
      complexes dose-dependently inhibited the enzyme with IC50 values between 0.8
      mumol/l ((triethylphosphine)gold chloride) and over 100 mumol/l (auranofin). None
      of the compounds affected phospholipase A2 from human polymorphonuclear
      leukocytes at concentrations up to 100 mumol/l. Inhibition of phospholipase C by
      (triethylphosphine)gold chloride, aurothiomalate, and compound 3 was not
      significantly different at substrate concentrations of 20 and 100 mumol/l
      phosphatidylinositol, suggesting that these gold complexes do not inhibit
      phospholipase C by competing with the substrate. After confirming the Ca2+
      dependence of the human platelet phospholipase C by demonstrating inhibition by
      the Ca2+ chelators EDTA and EGTA--but no inhibition by the Zn2+ chelator 1,10
      phenanthroline--the inhibition of the enzyme by (triethylphosphine)gold chloride,
      aurothiomalate, and compound 3 was studied at 3 different concentrations of Ca2+
      in the range of 0.2 to 2 mmol/l. Inhibition by (triethylphosphine)gold chloride
      was not affected by changes of Ca2+, whereas inhibition by aurothiomalate and
      compound 3 was markedly suppressed by increasing the Ca2+ concentration.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1353960
TI  - Alterations in expression and structure of the DNA repair gene XRCC1.
AB  - The repair-associated gene XRCC1 was previously cloned by complementing the
      hamster mutant EM9, which has a high rate of spontaneous SCE and hypersensitivity
      to DNA damaging agents. In analyzing XRCC1 gene expression, similar levels of
      steady-state mRNA were found in normal cells, Bloom's syndrome cells with altered
      SCE, and in squamous carcinoma cells with differential X-ray sensitivity. An
      EcoRI restriction fragment-length polymorphism previously identified in XRCC1 did
      not correlate with the repair phenotypes of these cells. The mRNA of XRCC1
      decreased to 20-40% after treatment of cells with a DNA damaging agent. XRCC1
      also showed tissue specific expression in rats. The mRNA levels were high in
      testis (7-8 fold), ovary (3-4 fold) and brain (4-5 fold), when compared with
      those in intestine, liver and spleen (1-2 fold). These data and the high levels
      of XRCC1 protein detected in testis indicate that XRCC1 may play an important
      role in DNA processing during meiogenesis and recombination in germ cells.

PMID- 1353964
TI  - 9th International Conference on Methods in Protein Sequence Analysis. Otsu,
      Japan, September 20-24, 1992. Abstracts.

PMID- 1353963
TI  - Dyskinesia and neuroleptic exposure in elderly psychiatric inpatients.
AB  - A wide variation in prevalence rates of tardive dyskinesia and spontaneous
      orofacial dyskinesia has been reported in the elderly. To clarify these
      discrepancies, we studied 45 patients over the age of 60 years admitted to a
      short-term psychiatric unit. Standardized criteria for the diagnosis of
      dyskinesia were used. We found a rate of tardive dyskinesia of only 21% (7/33) in
      our patients having a history of neuroleptic exposure. We found no cases (0/12)
      of spontaneous orofacial dyskinesia. There was a significant association between
      tardive dyskinesia and psychiatric diagnosis, with the highest rate of tardive
      dyskinesia in those patients with schizophrenic disorders, followed by those with
      organic disorders and mood disorders, respectively. There was also a significant
      association between the presence of tardive dyskinesia and radiographic evidence
      of cortical atrophy, and a trend towards an association with leukoencephalopathy.
      Our results suggest that published rates of tardive and spontaneous dyskinesia in
      the elderly may overestimate the prevalence of these disorders, especially among
      geriatric patients with acute psychiatric presentations.

PMID- 1353965
TI  - Expression of c-erb B-2/neu proto-oncogene in human prostatic cancer tissues and
      cell lines.
AB  - Both amplification and overexpression of c-erb B-2/neu have been associated with
      the progression and possible prognosis of a number of human cancers. In this
      study, we demonstrated that c-erb B-2/neu may also play an important role in
      human prostate cancer. Our conclusion is based on the following observations: (1)
      A monoclonal antibody raised against a peptide sequence from the C-terminal
      domain of the human c-erb B-2/neu gene product reacted positively with 68.7% (11
      of 16) of the human prostatic cancer tissue extracts analyzed by western blot
      procedure. These results were supported by the immunohistochemical staining of
      the prostatic cancer specimens; 80% (12 of 15) showed positive staining,
      primarily around the plasma membranes of the prostatic cancer cells. c-erb B
      2/neu oncoprotein was not detectable in normal prostate tissues (five examined by
      immunohistochemical staining and three by western blotting) or in human benign
      prostatic hyperplasia (two examined by immunohistochemical staining and six by
      western blotting) and was expressed less abundantly with lower intensity in
      "normal" human prostate tissues adjacent to cancerous prostate tissue (5 of 12
      examined by immunohistochemical staining). We observed no evidence of c-erb B
      2/neu gene amplification in 10 fresh human prostatic cancer specimens examined by
      Southern blotting and in the cultured human prostatic cancer cell lines PC-3, DU
      145, and LNCaP. (2) The c-erb B-2/neu protein was detected in both androgen
      receptor-positive (LNCaP) and -negative (PC-3 and DU-145) human prostate cancer
      cell lines. Positive immunostaining of c-erb B-2/neu protein was found to be
      associated predominantly with the plasma membranes of PC-3 cells, but was also
      found to be widespread in the cytoplasmic region of the LNCaP cells and in the
      perinuclear region of the DU-145 cells. (3) Like prostate-specific antigen (PSA)
      expression, c-erb B-2/neu mRNA expression was also positively regulated by
      androgen in androgen-receptor-positive LNCaP cells in vitro and LNCaP tumors in
      vivo. When LNCaP tumors were grown in castrated male hosts, levels of c-erb B
      2/neu and PSA mRNA expression decreased initially, but rebounded at 3 wk to
      levels comparable to those expressed by tumors maintained in intact adult male
      hosts.

PMID- 1353966
TI  - Multidrug resistance in human cancer.

PMID- 1353967
TI  - Glutathione S-transferase in chemotherapy resistance and in carcinogenesis.
AB  - Cytosolic glutathione S-transferases are composed of two monomeric subunits.
      These monomers are the products of different gene families designated alpha, mu,
      and pi. Dimerization yields either homodimeric or heterodimeric holoenzymes
      within the same family. The members of this complex group of proteins have been
      linked to the detoxification of environmental chemicals and carcinogens, and have
      been shown to be overexpressed in normal and tumor cells following exposure to
      cytotoxic drugs. They also are overexpressed in carcinogen-induced rat liver
      preneoplastic nodules in rat liver. In all of these cases, the changes in
      expression of glutathione S-transferases are paralleled by increased resistance
      to cytotoxic chemicals. The degree of resistance is related to the substrate
      specificity of the isozyme. The relationship of the glutathione S-transferase
      genes to drug resistance has been directly demonstrated by gene transfer studies,
      where cDNAs encoding the various subunits of glutathione S-transferase have been
      transfected into a variety of cell types. This review discusses the results of
      numerous studies that associate resistance to alkylating agents with
      overexpression of protective detoxifying glutathione S-transferase enzymes.

PMID- 1353968
TI  - Multifactorial resistance to antineoplastic agents in drug-resistant P388 murine
      leukemia, Chinese hamster ovary, and human HeLa cells, with emphasis on the role
      of DNA topoisomerase II.
AB  - The role of DNA topoisomerase II in multifactorial resistance to antineoplastic
      agents is reviewed. We have previously observed that in Adriamycin (ADR)
      resistant P388 murine leukemia cells, DNA topoisomerase II enzyme content and
      cleavage and catalytic activities were all reduced and correlated with drug
      sensitivity. A subsequent study provided evidence for an allelic mutation of the
      gene for DNA topoisomerase II as a possible molecular mechanism underlying the
      enzyme alterations. To ascertain how universal were these observations, a study
      was undertaken of DNA topoisomerase II (topo II) in other cell lines resistant
      either to ADR or another topo-II-interactive drug, mitoxantrone. In ADR-resistant
      Chinese hamster ovary (CHO) cells, topo II cleavage and catalytic activities and
      the gene product were all reduced; however, only cleavage activity correlated
      with drug sensitivity. No differences were noted between ADR-sensitive and 
      resistant CHO cells by Northern or Southern blot analysis, raising the
      possibility that the enzyme in resistant cells may be regulated at a
      posttranscriptional level. Findings on a gel retardation or immunoblot band
      depletion assay showed that the enzyme in CHO/ADR-1 cells failed to bind to the
      DNA-drug-enzyme complex, suggesting a qualitative as well as quantitative enzyme
      alteration in those cells. Mitoxantrone-resistant HeLa cells (Mito-1) displayed
      not only a lower level of cleavage activity but also of enzyme content and
      catalytic activity, relative to the parental drug-sensitive HeLa cells. As with
      the CHO cells, no differences were noted between mitoxantrone-sensitive and 
      resistant HeLa cells on Northern and Southern blot analyses, suggesting that
      enzyme regulation in these resistant cells may also be at a posttranscriptional
      level. There was no evidence of enzyme binding to DNA-drug-enzyme complex in
      resistant HeLa/Mito-1 cells, once again suggesting the presence of a qualitative
      enzyme alteration. The findings in both ADR-resistant CHO cells and mitoxantrone
      resistant HeLa cells do not exclude the possibility that subtle changes in the
      topoisomerase II gene, such as point mutations, may account for these enzyme
      changes. The apparent qualitative changes observed in enzyme may result from
      posttranslational modifications such as phosphorylation.

PMID- 1353969
TI  - L-histidinol in experimental cancer chemotherapy: improving the selectivity and
      efficacy of anticancer drugs, eliminating metastatic disease and reversing the
      multidrug-resistant phenotype.
AB  - Human cancer chemotherapy is limited by two major problems: the failure of
      commonly used anticancer drugs to act against tumor cells in a specific manner
      and the ability of malignant cells to resist killing by antineoplastic agents.
      Experimentally, both of these problems can be solved by using L-histidinol in
      combination with conventional anticancer drugs. A structural analogue of the
      essential amino acid L-histidine and an inhibitor of protein biosynthesis. L
      histidinol improves the selectivity and the efficacy of a variety of cancer drugs
      in several transplantable murine tumors. Furthermore, L-histidinol circumvents
      the drug-resistant traits of a variety of cancer cells, including those showing
      multidrug resistance. This review will summarize these properties of L
      histidinol, present new evidence on its ability to increase the vulnerability of
      both drug-sensitive and drug-resistant human leukemia cells to various anticancer
      drugs, and show that, in addition to inhibiting protein synthesis, L-histidinol
      acts as an intracellular histamine antagonist. The establishment of a connection
      between the latter mechanism and the capacity to modulate anticancer drug action
      has resulted in a clinical trial in the treatment of human cancer.

PMID- 1353970
TI  - Microtubule distribution during fertilization in the rabbit.
AB  - The distribution of microtubules was studied during fertilization of the rabbit
      oocyte by immunofluorescence microscopy after staining with an anti-alpha-tubulin
      antibody. In ovulated oocytes, microtubules were found exclusively in the meiotic
      spindle. At fertilization, the paternal centrosome generated sperm astral
      microtubules. During pronuclear development, the sperm aster increased in size,
      and microtubules extended from the male pronucleus to the egg center and towards
      the female pronucleus. These observations indicate that microtubules emanating
      from the sperm centrosome were involved in the movements leading to the union of
      the male and female pronuclei. At late pronuclear stage, microtubules surrounded
      the adjacent pronuclei. The mitotic spindle that emerged from the perinuclear
      microtubules contained broad anastral poles.

PMID- 1353972
TI  - G protein-coupled mechanisms and nervous signaling.

PMID- 1353971
TI  - Multiple sites of Hox-7 expression during mouse embryogenesis: comparison with
      retinoic acid receptor mRNA localization.
AB  - We report results from a study of Hox-7 expression during mouse embryonic and
      fetal development and compare the localization of Hox-7 transcripts with those of
      the retinoic acid receptors. Transcripts were detected by in situ hybridization.
      Hox-7 expression occurs in (1) cephalic neural crest and its derivatives, (2)
      sites of ectomesodermal interaction, (3) extraembryonic tissues, and (4)
      endocardial cells. Hox-7 does not seem to be involved in defining rostrocaudal
      boundaries, but instead appears to be expressed along the proximodistal axes at
      these sites. We further investigated the active sites of morphogenesis, which
      involve an ectomesodermal interaction (e.g., limb buds, visceral arches),
      including genital tubercle and tail ridge. These are regions highly positive for
      Hox-7 transcripts, and many are known to be sites for the expression of gamma
      retinoic acid receptors (RARs) and cellular retinoic acid binding proteins. Most
      regions that express Hox-7 are subregions of gamma-RAR expression. In the
      developing limb bud, expression of Hox-7 takes place in the interdigital region,
      where it overlaps areas of beta-RAR expression.

PMID- 1353973
TI  - c-fos proto-oncogene expression in bronchial biopsies of asthmatics.
AB  - c-fos, a proto-oncogene regulating the transcription of many genes, plays a
      critical role in the cell cycle and differentiation and may be involved in the
      regulation of inflammation in asthma. Very low levels of c-fos are detectable in
      most human cells, and its expression is rapidly and transiently increased by
      multiple factors, some of which are involved in the airways inflammation of
      asthma (histamine, eicosanoids, and cytokines). The presence of c-fos protein, as
      detected by immunofluorescence, and the immunoreactivity of PCNA, a cell
      proliferation marker, were examined in bronchial biopsies obtained from 12
      asthmatics and 10 normal subjects. Biopsies of eight of 12 asthmatics expressed c
      fos versus none of 10 normal subjects. The expression was heterogeneous and
      localized to cells positive for anti-cytokeratin monoclonal antibody, indicating
      their epithelial origin. On the other hand, PCNA immunoreactivity was only
      observed in one asthmatic and one control subject but it was not related with c
      fos expression. This study demonstrates the induction of c-fos in epithelial
      cells of asthmatics, suggesting a role for this proto-oncogene in activation
      rather than in proliferation.

PMID- 1353974
TI  - The role of CD18-mediated adhesion in neutrophil sequestration induced by
      infusion of activated plasma in rabbits.
AB  - Infusion of activated plasma induces neutropenia and sequestration of neutrophils
      within the microvasculature. This study examined the role of the adhesion
      glycoprotein complex, CD11/CD18, in this sequestration. Rabbits pretreated with
      either the anti-CD18 monoclonal antibody (mAb) 60.3 or saline were given
      infusions of zymosan-activated plasma (ZAP) or saline. The effect of mAb 60.3 on
      the changes in circulating neutrophil counts, radiolabeled neutrophil kinetics in
      the lung, and the pulmonary microvascular accumulation of neutrophils induced by
      ZAP infusion was determined. The data show that pretreatment with mAb 60.3 did
      not inhibit either the rate of onset or the severity of the neutropenia but
      prevented the sustained neutropenia. In addition, mAb 60.3 completely prevented
      the ZAP-induced changes in radiolabeled neutrophil kinetics and largely inhibited
      the accumulation of neutrophils within the capillaries and the small vessels when
      evaluated after 15 min of ZAP infusion. We conclude that neutrophil accumulation
      is a two-step process, the first occurring through a CD18-independent mechanism
      that may involve a stimulus-induced decrease in neutrophil deformability and acts
      to slow neutrophil transit through the lung. The second step requires CD18
      dependent adhesion and is needed for prolonged accumulation of neutrophils within
      the pulmonary microvasculature.

PMID- 1353975
TI  - Expression and function of beta 2 integrins on alveolar macrophages from human
      and nonhuman primates.
AB  - The alveolar macrophage (AM) participates in diverse, adherence-related
      activities required for host defense and the inflammatory response. The beta 2
      integrins (the CD11/CD18 heterodimer) mediate some of these activities on
      circulating leukocytes and peritoneal macrophages. We investigated expression of
      the CD11/CD18 leukocyte integrin subunits on AMs obtained by bronchoalveolar
      lavage of human and nonhuman primates. We also determined the role of the
      CD11/CD18 complex in AM chemotaxis and adherence to A549 alveolar epithelial cell
      monolayers. Immunofluorescence flow cytometry indicated that the CD11a/CD18
      complex was expressed in high levels and CD11b/CD18 and CD11c/CD18 in lower
      levels on the AM surface. Northern blot analysis indicated the presence of CD11a,
      CD11c, and CD18 mRNA in the AMs. Smaller quantities of CD11b mRNA were also
      found. AM chemotaxis to zymosan-activated serum was markedly inhibited by a
      monoclonal antibody to CD18. In addition, adherence of AMs to A549 cells
      (stimulated by tumor necrosis factor to upregulate intercellular adhesion
      molecule-1 expression) was decreased from 30.3 +/- 5.0 to 20.8 +/- 2.4% (P less
      than 0.05) by the same monoclonal antibody. We conclude that: (1) AMs obtained
      from human and nonhuman primates constitutively express predominantly CD11a/CD18
      surface antigen and mRNA, (2) chemotaxis of AMs is CD18 dependent, and (3)
      adhesion of AMs to an alveolar epithelial cell monolayer is partly but not
      completely dependent on the beta 2 integrins.

PMID- 1353976
TI  - Induction of ICAM-1 expression on human airway epithelial cells by inflammatory
      cytokines: effects on neutrophil-epithelial cell adhesion.
AB  - Inflammation of the human airways in diseases such as chronic bronchitis, cystic
      fibrosis with Pseudomonas endobronchial infection, and possibly asthma during
      late-phase reactions involves a local influx of neutrophils (PMN) that may
      participate in airway epithelial injury. PMN-mediated cellular injury is most
      efficient under conditions of PMN-target cell adhesion. PMN express adhesive
      glycoproteins of the CD11/CD18 family that are counter-receptors for
      intercellular adhesion molecule-1 (ICAM-1), found on various cell types. We
      proposed that adherence by PMN to human airway epithelial cells via ICAM-1 might
      be an important mechanism in inflammatory airway diseases. We found that although
      PMN adhere poorly (less than 5%) to monolayers of human tracheal epithelial cells
      (TEC) in primary culture, they adhere readily (45 to 50%) to an SV40-immortalized
      line of human TEC, designated 9HTEo-. We also found 6-fold greater surface
      expression of ICAM-1 on 9HTEo- compared with primary TEC. Blocking surface ICAM-1
      on 9HTEo- cells with specific monoclonal antibody inhibited PMN adherence by
      about 50%. Thus, ICAM-1 plays a major role in this adherence, although it is
      possible that other epithelial ligands contribute also. Antibodies to CD11a,
      CD11b, and CD18 on PMN also inhibited PMN-epithelial adherence. Treatment of
      primary TEC monolayers with the proinflammatory cytokines interleukin-1 (IL-1) or
      tumor necrosis factor-alpha (TNF-alpha) caused a 3- to 4-fold increase in both
      cell surface ICAM-1 expression and support of PMN adhesion.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1353977
TI  - Coronary "open" endarterectomy and reconstruction: short- and long-term results
      of the revascularization with saphenous vein versus IMA-graft.
AB  - From June 1984 to December 1990, 96 patients underwent "open" coronary
      endarterectomy and reconstruction. In 50 patients (group 1), a saphenous vein
      (SV) graft was used to reconstruct and bypass 54 coronary vessels. In 46 patients
      (group 2), 46 coronary vessels were reconstructed with an SV patch and then
      bypassed with the internal mammary artery (IMA): Seventy-four LAD coronary
      arteries (36 in group 1 and 38 in group 2) were treated with these procedures.
      Operative mortality was 8% in group 1 and 2.1% in group 2. Five patients (10%) in
      group 1 and 1 patient (2.1%) in group 2 developed perioperative myocardial
      infarction. The early postoperative patency of the reconstructed vessels was
      84.6% in group 1 and 92.5% in group 2. Angiographic controls were performed
      between 30 and 36 months after operation in 18 patients (72%) of group 1 and in
      16 patients (69%) of group 2 with patency rates of 66.7% and 81.5%, respectively.
      A further angiographic study performed between 54 and 60 months after operation
      of 9/22 patients of group 1 and 5/9 patients of group 2 did not show any
      additional closure of the endarterectomized vessels. Three- and 5-year survival
      analyzed by the Kaplan-Meier method was 79.6% and 69.7%, respectively, in group 1
      and 86.8% for both the 3- and 5-year survival in group 2. After a mean follow-up
      of 51.0 and 35.5 months, 62.8% of the surviving patients of group 1 and 75.6% of
      group 2 were asymptomatic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1353978
TI  - Internal mammary artery bypass graft for impaired coronary perfusion after
      neonatal arterial switch operation.
AB  - Myocardial ischaemia caused by perfusion impairment of translocated coronary
      arteries is the major cause of perioperative mortality after neonatal arterial
      switch operation for transposition of the great arteries. We report the
      successful use of the right internal mammary artery as a bypass graft to a
      dominant right coronary artery to treat insufficient perfusion of this artery in
      a newborn. Eight months later, coronary angiography showed a full blood supply of
      the right coronary artery across the internal mammary anastomosis. After a follow
      up period of more than 30 months, somatic development, electrocardiogram and
      echocardiographically determined contractility of both ventricles are practically
      normal indicating regular function of the bypass graft.

PMID- 1353980
TI  - [National congress 1992].

PMID- 1353979
TI  - An immunohistochemical study on the pancreatic endocrine cells of the three-toed
      sloth, Bradypus variegatus.
AB  - The cellular composition and relative frequency of the occurrence of pancreatic
      endocrine cells were studied immunohistochemically in a primitive eutherian and
      arboreal folivore, the three-toed sloth, since previous histochemical and
      ultrastructural studies on the endocrine pancreas of the sloth have detected only
      a single islet cell type, the A cell. In the sloth pancreas, four types of
      endocrine cells immunoreactive for glucagon, insulin, somatostatin and serotonin
      (5-hydroxytryptamine) were found as reported in the pancreas of human and common
      experimental mammals, but pancreatic polypeptide-immunoreactive cells were not
      detected by either avian- or bovine-pancreatic polypeptide antiserum. The
      endocrine cells were distributed mainly in the islets and partly also in the
      exocrine tissue including the pancreatic ducts. Larger or smaller clusters
      consisting of glucagon- and insulin-immunoreactive cells were also found
      frequently in the interlobular connective tissue. In the islets, glucagon- and
      insulin-immunoreactive cells were the most prominent cell type, while
      somatostatin- and serotonin-immunoreactive cells were sparse. The most striking
      feature in the sloth pancreas is the high frequency of glucagon-immunoreactive
      cells, because these cells are by far less in number than insulin-immunoreactive
      cells in the islets of human and common experimental mammals. This appears to be
      an intriguing characteristic of the sloth pancreas in a possible relation to the
      animal's unique metabolic system and the phylogenetical position.

PMID- 1353981
TI  - Clinical characteristics of haemorrhagic fever with renal syndrome in children.
AB  - From January 1988 to September 1989, seven patients (4 girls and 3 boys, aged 3
      12 years) with haemorrhagic fever with renal syndrome (HFRS) were hospitalised at
      the University Children's Hospital in Belgrade. In four patients the disease
      appeared as a family outbreak, the others were sporadic cases. In six patients
      the clinical presentation was suggestive of HFRS, as they had fever with
      headache, myalgia, sore throat and gastrointestinal illness followed by renal
      abnormalities. However, severe haemorrhagic syndrome with petechia, haematoma,
      haematemesis and melaena was present in one patient only. Renal disease presented
      as nephritic syndrome and/or acute renal failure. Five patients recovered after 2
      3 weeks without sequellae, one patient had decreased renal function 17 months
      after the start of the disease and the remaining patient died. In six patients
      the diagnosis of HFRS was confirmed serologically by a significant rise in
      antibody titres against hantaviruses, while in the patient with the fetal and
      fulminant course of the disease, the diagnosis was established on the basis of
      epidemiological and autopsy findings. We suggest that children living in endemic
      areas who develop an ill-defined, febrile and gastrointestinal disease with renal
      dysfunction should be evaluated for HFRS.

PMID- 1353982
TI  - Expression and modification of Hox 2.1 protein in mouse embryos.
AB  - A polyclonal antibody, alpha Hox 2.1a, has been generated and used to
      immunolocalize Hox 2.1 protein in mouse embryos. Protein is present in nuclei of
      all tissues previously shown to express Hox 2.1 RNA. In addition, protein is seen
      in somites and proximal regions of the limb buds, tissues in which Hox 2.1 RNA
      expression was not clearly detected previously by in situ hybridization. At the 7
      somite stage, protein is detectable in the neural tube up to the level of somite
      1, but later retracts to a more posterior position. Immunoblot, in vitro
      translation, and immunoprecipitation experiments were carried out to characterize
      the Hox 2.1 protein. The results show that the Hox 2.1 gene produces at least two
      related phosphorylated proteins present in different proportions in different
      tissues.

PMID- 1353983
TI  - Hox-3.6: isolation and characterization of a new murine homeobox gene located in
      the 5' region of the Hox-3 cluster.
AB  - Most members of the murine Hox gene system can be grouped into two subclasses
      based on their structural similarity to either one of the Drosophila homeotic
      genes Antennapedia (Antp) or Abdominal B (AbdB). All the AbdB-like genes reported
      thus far are located in the 5' region of their respective cluster. We describe
      here the isolation, structural characterization and spatio-temporal expression
      pattern of a new AbdB-like homeobox gene designated Hox-3.6 that is located in
      the 5' region of the Hox-3 cluster. Hox-3.6 has an extreme posterior expression
      domain in embryos of 12.5 days of gestation, a feature that has thus far only
      been observed for the 5' most genes of the Hox-4 cluster. Like the other members
      of the AbdB subfamily, Hox-3.6 exhibits spatially restricted expression in the
      hindlimb bud, but the expression domain is antero-proximal in contrast to the
      postero-distal domain reported for its cognate gene Hox-4.5. Structural analysis
      of the 5' region revealed the presence of a 35 bp sequence which shares homology
      and relative 5' position with an upstream sequence present in its two nearest
      downstream neighbors, Hox-3.2 and -3.1.

PMID- 1353984
TI  - Euro-Canadian study with taxol hits a record.

PMID- 1353985
TI  - Maturation of CD4-8- alpha/beta TCR+ T cells induced by CD2-stimulation in vivo
      and in vitro.
AB  - Newly generated ('virgin') rat thymocytes of the immature CD4+8+ double positive
      (DP) subset were treated in suspension culture for 2 days with the stimulatory
      pair of anti-CD2 monoclonal antibodies OX-54 and OX-55. Approximately 50% of the
      recovered cells had downregulated CD4 and CD8 and upregulated the T cell antigen
      receptor (TCR). CD2-stimulated, but not control thymocytes proliferated in
      response to TCR plus IL-2 stimulation. In vivo, postnatal injection of OX-54/55
      led to a dramatic and selective increase in functionally mature CD4-CD8- double
      negative (DN) alpha/beta--TCR(high) thymocytes and peripheral T cells. These
      findings show that CD2 stimulation can promote T cell differentiation and suggest
      that DN TCR(high) thymocytes can be generated from DP thymocytes via alternative
      pathways of T cell maturation.

PMID- 1353986
TI  - Anesthesia considerations in thoracic trauma.

PMID- 1353987
TI  - Interleukin-2 induces tumor necrosis factor-alpha production by activated human T
      cells via a cyclosporin-sensitive pathway.
AB  - We examined requirements for TNF-alpha production by purified human blood T
      cells, completely depleted of monocyte-accessory cells, under different
      conditions of stimulation. Activation of T cells with immobilized anti-CD3
      induced the appearance of mRNA for TNF-alpha and of functionally active TNF-alpha
      in the culture supernatant. Anti-CD3-induced TNF-alpha production could be
      inhibited by blocking the IL-2R with a combination of anti-Tac and Mik beta 1
      (mAbs against the p55 and p75 chain of the IL-2R respectively) thus indicating an
      essential role of IL-2 in TNF-alpha induction. When purified T cells were
      activated with a combination of two anti-CD2 mAbs (9-1 and 9.6), additional
      signals (rIL-2 or rIL-1 beta or anti-CD28) were required for TNF-alpha mRNA
      production and protein secretion. rIL-1 beta supported anti-CD2-induced TNF-alpha
      production indirectly through an IL-2-dependent pathway. These same helper
      signals also enhanced TNF-alpha production by anti-CD3-stimulated T cells. IL-4,
      IL-6, GM-CSF and IFN-gamma had no effect on TNF-alpha production by T cells
      activated via either pathway. Addition of rIL-1 beta alone, rIL-2 alone or
      endotoxins to resting human T cells did not induce detectable amounts of TNF
      alpha. Both helper/inducer CD4(+) and suppressor/cytotoxic CD8(+) subsets of T
      cells were shown to produce TNF-alpha upon stimulation. We conclude that CD3 or
      CD2 triggering are not sufficient for TNF-alpha production by T cells, but that
      the latter is dependent (apparently at the transcriptional level) on the
      interaction of IL-2 with its functionally active cell surface receptors. We could
      further demonstrate that TNF-alpha production was completely blocked by
      cyclosporin A. The inhibitory effect of this agent on TNF-alpha production was
      also observed in the presence of rIL-2, thus excluding an indirect effect through
      inhibition of IL-2 production.

PMID- 1353988
TI  - Florence: cytokines and T-cell subsets.
AB  - The second international congress on cytokines, held in Florence (March 23-25,
      1992), has been marked by the presentation of recent data about cytokine
      deficient mice obtained by homologous recombination which, contrary to
      expectation, exhibit normal T and B cell development. The cloning of a few new
      cytokines and receptors were also reported as well as recent advances in the
      knowledge of the oldest members of this quickly growing family. The meeting has
      also been marked by a great number of reports providing insights into T cell
      dependent immune response. Participants provided evidence, through their
      different experimental models, that functional T helper dichotomy, TH1 versus
      TH2, was of physiological relevance both in mice and humans, while other reports
      highlighted the differential regulation of these T lymphocytes subsets. An
      interesting discussion took place about their differentiation process and the
      harmonization of the concepts of naive, memory and effector T cells with the T
      subset classification according to cytokine production profile.

PMID- 1353989
TI  - What's new about tumor necrosis factors? Report on the fourth TNF International
      Congress.

PMID- 1353990
TI  - Clinical challenges in pediatric renal transplantation. Proceedings of 2nd North
      American Pediatric Renal Transplantation Cooperative Study (NAPRTCS) Workshop.
      Boston, April 17-18, 1991.

PMID- 1353991
TI  - Effect of dexmedetomidine, an alpha 2-adrenergic agonist, in the isolated heart.
AB  - Dexmedetomidine (DM) was studied in the isolated dog heart in the form of a
      Starling heart-lung preparation, (HLP). Hearts were subjected to increased
      loading by (a) increasing cardiac output, and (b) increasing systemic resistance.
      Results are depicted by cardiac function curves, prepared by plotting left atrial
      pressure against either systemic cardiac output or mean arterial pressure. DM,
      given in divided doses up to 44 micrograms, had no effect on heart rate or
      cardiac function, nor did injection of 0.5 mg of atipamezole, a selective alpha 2
      antagonist. Additional injections of very large doses of DM, up to 4,444
      micrograms, caused an increase in heart rate and a leftward shift of the function
      curves, ie, positive chronotropic and inotropic effects. Plasma catecholamine
      levels increased markedly between the 444 micrograms and the 4,444 micrograms
      cumulative doses of DM. Administration of 1 mg of prazosin had no effect, but 1
      mg of propranolol returned the rate to baseline and markedly shifted function
      curves to the right and depressed their slopes. Thus, whereas low doses
      (corresponding to between 1 and 30 micrograms/kg in intact animals) of DM, given
      acutely IV, have been shown to depress cardiac function in intact and denervated
      dogs, this effect is not due to a direct effect on the myocardium. High doses,
      far beyond doses maximally effective in intact animals and man, release
      catecholamines from cardiac stores. Plasma DM levels after low doses in the HLP
      were between 1 to 10 times those seen in intact animals and human volunteers
      after the usual doses given clinically for their central effects. Because DM
      caused no myocardial depressant effect in the isolated, blood-perfused canine
      HLP, decreases in cardiac function seen after this drug is given to intact and
      autonomically denervated dogs must be due to factor(s) other than a direct action
      on the myocardium.

PMID- 1353992
TI  - Combination of pancuronium and vecuronium.

PMID- 1353993
TI  - Possibility of HTLV-I transmission from wife with ATL to husband.

PMID- 1353994
TI  - Multidrug resistance (MDR1) in acute myelogenous leukemia: is it time to test?

PMID- 1353995
TI  - Identification of a point mutation in factor XIII A subunit deficiency.
AB  - Oligonucleotide primers have been designed for the amplification of all 15 exons
      of the human coagulation factor XIII A subunit gene. Each exon and its intron
      flanking regions has been amplified and sequenced from a patient with severe A
      subunit deficiency. A single G to A transition in the last base of exon 14 has
      been identified in the homozygous proband and in his heterozygous parents. The
      mutation would result in the substitution 681 Arg to His in the mature protein
      product. However, because the mutation is at a splice junction, the deficiency
      may result from a defect in pre-messenger RNA splicing.

PMID- 1353996
TI  - The skin as a target organ for the investigation of antiallergic drugs:
      comparison between cetirizine and terfenadine.
AB  - Two double-blind clinical pharmacology studies were performed in atopics in order
      to compare the inhibitory effects of cetirizine (CTZ) 2 HCl and terfenadine (TER)
      on histamine and antigen-induced skin reactions. In the first study, the subjects
      took single intakes of CTZ 10 mg and TER 60 mg. In the second study, they took
      CTZ 10 mg once a day and TER 60 mg b.i.d. for 3 weeks. CTZ was more effective
      than TER in inhibiting histamine skin reactivity. CTZ and TER were equally
      effective in inhibiting antigen-induced reactions. There was no tachyphylaxis,
      either for CTZ or for TER.

PMID- 1353997
TI  - Kimura's disease with marked proliferation of HLA-DR+CD4+ T cells in the skin,
      lymph node and peripheral blood.
AB  - A 41-year-old female had atopic dermatitis-like skin lesions since the age of 21,
      and for the past 6 years many skin tumors developed on the body, lower
      extremities and other areas. The histological picture of the tumor, eosinophilia
      and high IgE in the peripheral blood were consistent with a diagnosis of Kimura's
      disease. Although the tumors were markedly reduced by oral prednisolone
      administration, thereafter papules appeared disseminated over the body with
      swelling of superficial lymph nodes. Immunohistochemical examination indicated
      marked proliferation of HLA-DR+CD4+ T cells in the skin and lymph nodes, and two
      color flow cytometry confirmed it in the lymph nodes and peripheral blood.

PMID- 1353998
TI  - Peripheral blood stem cell transplantation: historical perspective, current
      status, and prospects for the future.

PMID- 1353999
TI  - Drugs for treatment of peptic ulcers.
AB  - Pharmacologic management of peptic ulcer disease continues to evolve with the
      introduction of diverse types of new therapeutic agents. The ideal aims of
      treatment of peptic ulcer disease are to relieve pain, heal the ulcer, and delay
      ulcer recurrence. This article provides a broad perspective on the pharmacology
      and therapeutic actions of antiulcer drugs. To date, no drug meets all goals of
      therapy. Drug treatment of peptic ulcers is targeted at either counteracting
      aggressive factors or stimulating the mucosal defense. Drugs that inhibit or
      neutralize gastric acid secretion include histamine H2-receptor antagonists,
      proton pump inhibitors, anticholinergics, prostaglandins, and antacids. H2
      receptor antagonists have become first-line drugs for treatment of uncomplicated
      duodenal ulcers, gastric ulcers, prevention of ulcer relapse, and mild
      esophagitis. However, H2-receptor antagonists, like other gastric
      antisecretory/antiulcer drugs, have high rates of ulcer recurrence following
      discontinuation of therapy. They therefore need to be administered continuously
      in patients prone to such recurrences. Omeprazole has emerged as a major drug for
      the treatment of severe erosive esophagitis, refractory ulcers, and Zollinger
      Ellison syndrome. The major disadvantage of proton pump inhibitors is the concern
      for their long-term safety. The roles of M1-antimuscarinic agents and antacids
      have not been fully defined. Misoprostol, effective for the treatment of gastric
      and duodenal ulcers, is now the only drug that prevents ulcers induced by
      nonsteroidal anti-inflammatory drugs. Mucosal protective drugs that do not
      inhibit gastric acid secretion include sucralfate and organic bismuth salts.
      Sucralfate is a nonsystemic, well-tolerated, effective drug for treatment of
      duodenal ulcers and prevention of duodenal ulcer relapse. The organic bismuth
      salt bismuth subcitrate is efficacious in the treatment of duodenal and gastric
      ulcers. Furthermore, it has also been established that it alters the course of
      ulcer recurrence. However, bismuth encephalopathy is a major toxicity concern
      that needs to be addressed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354000
TI  - [Progress on mechanism and countermeasure study on senility in China].

PMID- 1354001
TI  - [Symposium on image diagnosis of clinical traditional Chinese medicine syndrome
      and types of common diseases].

PMID- 1354002
TI  - Distinguishing neuroleptic malignant syndrome (NMS) from NMS-like acute medical
      illnesses: a study of 34 cases.
AB  - A study of 34 hospitalized patients with suspected neuroleptic malignant syndrome
      (NMS) found that 24 had NMS and the other 10 had acute, usually serious, medical
      problems. There were no demographic, psychopathologic, or treatment-related
      differences between the groups. NMS patients had more dehydration, cogwheeling,
      diaphoresis, disorientation, drooling, dysphagia, and rigidity and higher
      diastolic blood pressure. The groups had similar fevers, heart rates, creatine
      kinase levels, and white blood cell counts. Three non-NMS patients died during
      their acute illnesses. Results suggest that considering NMS as a diagnosis and
      ruling out other acute illnesses such as pneumonia are equally important when a
      patient on neuroleptic medication becomes medically ill.

PMID- 1354003
TI  - In the realm of the homeodomain.

PMID- 1354006
TI  - Lateral hypothalamic area neurotransmission and neuromodulation of the specific
      cardiac effects of insular cortex stimulation.
AB  - Microstimulation of the rat posterior insular cortex in phase with the ECG R wave
      elicits pure cardiac effects unaccompanied by changes in blood pressure or
      respiration. This technique has successfully demonstrated cardiac chronotropic
      organisation and arrhythmogenesis within the insula. Pathways exist linking the
      insular cortex with the lateral hypothalamic area (LHA). Similarly, the LHA has
      previously been shown to mediate the sympathetic and blood pressure effects of
      insular cortex stimulation. Therefore it was anticipated that the tachycardia
      elicited by insular phasic microstimulation would be responsive to LHA
      manipulations. Insular tachycardia sites in 28 chloralose-anesthetised male
      Wistar rats were phasically stimulated once with each cardiac cycle using 500
      microA for 1 min before and after microinfusions (390 nl) into the LHA. The
      insular tachycardia response was abolished by LHA microinfusions of the synaptic
      blocker cobaltous chloride (4 mM). LHA microinjection of kynurenic acid (250 mM)
      attenuated insular tachycardia by 95%. Microinjection of naloxone (30 mM)
      similarly attenuated the tachycardia by 95%. Met-enkephalin (3.5 mM) was without
      effect on this response whereas Leu-enkephalin (3.5 mM) and neuropeptide Y (0.01
      mM) (NPY) doubled the magnitude of the tachycardia. Dynorphin (0.12 mM), a
      specific kappa opioid receptor agonist, augmented the response to stimulation of
      insular tachycardia sites 8-fold. Consequently, it is suggested that the LHA
      contains an obligatory synapse mediating insular tachycardia and that glutamate
      is the likely neurotransmitter at this site. Neuromodulation of insular
      tachycardia may be effected by opiate kappa and NPY receptors, a finding of
      considerable clinical relevance.

PMID- 1354004
TI  - Effects of ionizing radiation on a plant genome: analysis of two Arabidopsis
      transparent testa mutations.
AB  - Ionizing radiation is known to cause chromosomal alterations such as inversions
      and deletions and has been used extensively for inducing mutations. In
      Arabidopsis, two methods for the isolation of genes identified on the basis of
      mutant phenotypes--genomic subtraction and chromosome walking--either rely on or
      are greatly facilitated by the availability of these types of mutations. This
      article gives a detailed characterization of ionizing radiation-induced mutations
      in plants. The Arabidopsis genes encoding chalcone flavanone isomerase (CHI) and
      dihydroflavonol 4-reductase (DFR) were cloned and found to correspond to two
      transparent testa loci. A CHI allele, generated by fast-neutron irradiation,
      consisted of an inversion within the gene. A 272-bp fragment from 38 centimorgans
      away on the same chromosome was transferred to one end of this inversion. A DFR
      allele, induced by x-irradiation, contained two deletions and an inversion of the
      2.8-centimorgan intervening region. Sequence analysis of the break points in both
      mutants indicate that repair of radiation-induced damage involves mechanisms
      similar or identical to those that mediate the integration of foreign sequences
      into the genome. The chromosome rearrangements found in these mutants have
      important implications for the use of ionizing radiation-induced alleles in
      classical and molecular genetic experiments in plants.

PMID- 1354005
TI  - Role of NMDA receptors in hypothalamic facilitation of feline defensive rage
      elicited from the midbrain periaqueductal gray.
AB  - The present study tested the hypothesis that the pathway from the medial
      hypothalamus to the midbrain periaqueductal gray (PAG) subserving defensive rage
      behavior in the cat facilitates the occurrence of this response when elicited
      from the PAG by utilizing excitatory amino acids as a neurotransmitter or
      neuromodulator. Cannula electrodes were implanted into the PAG for the
      elicitation of defensive rage behavior as well as for microinjections of
      excitatory amino acid antagonists and N-methyl-D-aspartic acid (NMDA). Monopolar
      stimulating electrodes were also implanted into the medial hypothalamus from
      which this response could also be elicited and, when stimulated at subthreshold
      levels for elicitation of behavior, could also facilitate the occurrence of PAG
      elicited defensive rage. Initially, dual stimulation of the PAG and medial
      hypothalamus facilitated the occurrence of defensive rage elicited from the PAG.
      Then, the identical dual stimulation paradigm was repeated with the same current
      parameters following the infusion of various antagonists for different receptors
      into the PAG defensive rage sites. The results indicate that infusion of either
      kynurenic acid [(0.1-2.0 nmol), a non-selective excitatory amino acid receptor
      antagonist] or D-2-amino-7-phosphonoheptanoic acid (AP7) [(0.1-2.0 nmol), a
      specific NMDA receptor antagonist], produced a dose and time dependent blockade
      of the facilitatory effects of medial hypothalamic stimulation. In contrast,
      microinjections of relatively larger doses of 6-cyano-7-nitroquinoxaline-2,3
      dione (CNQX) [(4 nmol), a non-NMDA receptor (quisqualate and kainate) antagonist]
      or atropine [(4.4 nmol), a muscarinic receptor antagonist] had little effect upon
      medial hypothalamically elicited facilitation of the PAG response. In a second
      experiment, NMDA [0.1-1.0 nmol] was microinjected directly into PAG defensive
      rage sites in the absence of medial hypothalamic stimulation. In these animals,
      drug infusion mimicked the effects of dual stimulation by producing a dose and
      time dependent decrease in response latencies. A third experiment was designed to
      further test the hypothesis by neuroanatomical methods. Here, the retrograde
      label, Fluoro-Gold, was microinjected into defensive rage sites within the PAG
      and following a survival time of 5-6 days, the animals were sacrificed. The
      brains were then processed for immunocytochemical analysis of cells that
      immunoreact positively for aspartate and glutamate. The results indicated the
      presence of many retrogradely labelled and immunocytochemically positive cells
      within the rostro-caudal extent of the medial hypothalamus as well as others that
      were double labelled.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1354007
TI  - Somatotopic organization of tyrosine hydroxylase expression in the rat locus
      coeruleus: long term effect of RU24722.
AB  - Tyrosine hydroxylase (TH) tissue concentration was determined by immunostaining
      of tissue sections directly transferred onto nitrocellulose membranes in the
      restricted region of the noradrenergic perikarya of the locus coeruleus (LC)
      along its postero-anterior axis. TH containing cells were systematically counted
      on adjacent post fixed sections stained by immunohistochemistry. The absolute
      quantity of TH was estimated in each section and was found to be linearly related
      to the number of TH immuno-positive cells found in the adjacent section. The
      ratio between these two parameters was thus used as an index of the cellular
      concentration of TH in noradrenergic cells. In the LC of control rats, the TH
      cellular concentration was lower (-39%) in the anterior than in the posterior
      half of the structure. Three days after an injection of 20 mg/kg of RU24722, an
      eburnamine derivative known to increase the quantity of TH in the LC, increases
      in quantities of TH were found in both portions of the LC. Moreover in the
      posterior LC the increase in the amount of TH resulted from a significant
      increase in the number of TH-immunopositive cells. In the anterior part, however,
      it was primarily the result of a significant increase in TH cellular
      concentration. Throughout the LC there was an increase in the cellular
      concentration of TH which was inversely proportional to the concentrations found
      in control animals. TH mRNA content was measured by a quantitative in situ
      hybridization in sections of both the posterior and anterior LC one day after a
      single injection of RU24722 at the same dose. The quantity of TH mRNA was
      significantly increased in both parts. The number of TH mRNA-expressing neurons
      also increased, especially in the anterior LC. Thus the effects at the level of
      TH protein and TH mRNA were strikingly parallel though increase in TH protein
      occurred later than the increase in the TH mRNA. These results suggest that in
      the rat LC: (1) there is a significant population of 'sleeping cells' in which TH
      expression is either inactivated or, at a low level of activation; (2) TH
      cellular concentration could exert a retrocontrol on its own expression in cells
      of the LC that contained TH and (3) TH expression appears to be regulated by
      different selective mechanisms in these two different subpopulations of
      noradrenergic cells within the LC.

PMID- 1354008
TI  - Glutamate-immunoreactive synapses on retrogradely-labelled sympathetic
      preganglionic neurons in rat thoracic spinal cord.
AB  - Retrograde tracing with cholera toxin B subunit (CTB) combined with post
      embedding immunogold labelling was used to demonstrate the presence of glutamate
      immunoreactive synapses on sympathetic preganglionic neurons that project to the
      adrenal medulla or to the superior cervical ganglion in rat thoracic spinal cord.
      At the electron microscope level, glutamate-immunoreactive synapses were found on
      retrogradely labelled nerve cell bodies and on dendrites of all sizes. Two-thirds
      of the vesicle-containing axon profiles that were directly apposed to, or
      synapsed on, CTB-immunoreactive sympathoadrenal neurons were glutamate positive.
      The proportion of glutamate-immunoreactive contacts and synapses on
      sympathoadrenal neurons decreased to zero when the anti-glutamate antiserum was
      absorbed with increasing concentrations of glutamate from 0.1 mM to 10 mM. Double
      immunogold labelling for glutamate and gamma-aminobutyric acid (GABA) showed that
      glutamate-immunoreactive profiles did not contain GABA and that GABA
      immunoreactive profiles did not contain glutamate. These results suggest that
      glutamate is the major excitatory neurotransmitter to sympathoadrenal neurons and
      possibly to other sympathetic preganglionic neurons in the intermediolateral cell
      column of the spinal cord.

PMID- 1354009
TI  - Glutamate antagonists applied to midbody spinal cord segments reduce the
      excitability of the fictive rostral scratch reflex in the turtle.
AB  - Glutamate antagonists applied to the cutaneous-processing region of the rostral
      scratch circuit in turtles reduced the excitability of the rostral scratch
      reflex. Segments D3-D6 (D3 = 3rd postcervical) of the midbody spinal cord receive
      cutaneous afferents from the rostral scratch receptive field and perform the
      initial integration of this cutaneous sensory input. These cutaneous-processing
      segments are located anterior to the rostral scratch motor pattern generator that
      resides mainly in segments D7-D10 located in and near the hindlimb enlargement.
      We prepared 1 or 2 of the midbody segments for bath application of glutamate
      antagonists in preparations with a complete transection of the spinal cord
      anterior to segment D3. Each preparation was immobilized by neuromuscular
      blockade and fictive scratch motor output was recorded from hindlimb muscle
      nerves. Application of the NMDA N-methyl-D-aspartate) antagonist APV (D-2-amino-5
      phosphonovaleric acid, 50 microM) to a midbody segment significantly reduced the
      motor burst frequency of rostral scratch responses evoked by 3-Hz electrical
      stimulation of a site in that segment's dermatome. These data suggest that NMDA
      receptors contribute to cutaneous processing in the rostral scratch circuit.
      Application of APV to a midbody segment also reduced the magnitude of temporal
      summation in the scratch circuit in response to electrical stimuli delivered to
      the shell at 4- to 5-s intervals. Temporal summation was monitored at the level
      of hindlimb motor output as well as at the level of unit activity from 'long
      afterdischarge' neurons in the midbody segments. Our observations are consistent
      with the hypothesis that NMDA receptors contribute to the prolonged activation of
      'long-afterdischarge' neurons and the multisecond storage of excitation in the
      scratch reflex pathway.

PMID- 1354010
TI  - Kappa opiate receptors mediate tail-shock induced antinociception at spinal
      levels.
AB  - Previous work has demonstrated that 3 pharmacologically and neuroanatomically
      distinct analgesia systems can be sequentially activated by increasing numbers of
      transcutaneous tail-shock. To date, the categorization of the early (after 2 tail
      shocks) and late (after 80-100 tail-shocks) analgesias as opiate-mediated has
      been based on the ability of systemic naltrexone and morphine tolerance to block
      these effects. In contrast, the analgesia observed after 5-40 tail-shocks is
      unaffected by these manipulations, leading to its categorization as non-opiate.
      The present work and the following companion paper were aimed at identifying the
      neuroanatomical loci at which endogenous opiates exert their analgesic effects in
      this tail-shock paradigm and, further, to identify which opiate receptor subtypes
      are involved. The 3 experiments included in the present paper focus on the role
      of spinal opiates in tail-shock induced analgesia. The first experiment
      demonstrates that the tail-shock parameters used do not directly activate pain
      suppressive circuitry within the spinal cord, but rather activate centrifugal
      pain modulation circuitry originating within the brain. The last two experiments
      examine the effect of intrathecal microinjection of either naltrexone (a
      relatively non-selective opiate receptor antagonist), binaltorphimine (kappa
      receptor antagonist), Cys2-Tyr3-Orn5-Pen7-amide (CTOP) (mu receptor antagonist),
      or naltrindole (delta receptor antagonist). Taken together, these latter 2
      experiments demonstrate that both the early (after 2 shocks) and late (after 80
      100 shocks) opiate analgesias are mediated by kappa opiate receptors within the
      spinal cord.

PMID- 1354011
TI  - Effects of microtubule stabilization and destabilization on tau immunoreactivity
      in cultured hippocampal neurons.
AB  - Tau immunoreactivity is altered in neurofibrillary tangles (NFT) and degenerating
      neurites in Alzheimer's disease (AD). In addition, cytoskeletal proteins
      including tau are excessively phosphorylated in AD. Previous data indicated that
      calcium influx can cause antigenic changes in tau in cultured rat hippocampal and
      human cortical neurons similar to those seen in NFT. The present study used
      cultured hippocampal neurons to test the hypothesis that disruption of
      microtubules is a key event leading to altered antigenic properties of tau that
      result from calcium influx. As previously reported, we found that glutamate (100
      500 microM) and calcium ionophore A23187 (0.5-1 microM) elevated intraneuronal
      calcium levels and caused a reduction in microtubules, a marked increase in
      staining with Alz-50 and 5E2, and a decrease in tau-1 immunoreactivity. The
      microtubule-disrupting agent colchicine (1 microM) caused increased
      immunoreactivity of neurons towards tau antibodies Alz-50 and 5E2, and these
      effects of colchicine occurred in the absence of an increase in intracellular
      calcium levels. The microtubule-stabilizing drug taxol (100 nM) reduced neuronal
      immunoreactivity towards Alz-50 and 5E2 in untreated cultures and in cultures
      exposed to glutamate or A23187. Western blot analysis indicated that A23187
      caused a reduction in tau levels which was partially prevented by taxol,
      suggesting that tau associated with microtubules is less susceptible to calcium
      mediated degradation. Acid phosphatase treatment increased neuronal
      immunoreactivity towards tau-1 and reduced immunoreactivity towards Alz-50. The
      calcium-induced alterations in tau immunoreactivity were, and the colchicine
      induced alterations were not, affected by acid phosphatase treatment. Taken
      together, the data indicate that microtubule depolymerization can cause antigenic
      changes in tau similar to those seen in NFT independently of an increase in
      intraneuronal calcium levels. Stabilization of microtubules prevented the
      antigenic changes in tau suggesting that microtubules affect the availability
      and/or properties of epitopes on tau that are recognized by antibodies that stain
      NFT.

PMID- 1354013
TI  - Smooth muscle. Symposia of the Canadian Federation of Biological Societies.
      Kingston, Ontario, June 8-10, 1991.

PMID- 1354014
TI  - Proceedings of the 18th Collegium Internationale Neuro-Psychopharmacologium
      Congress. Nice, France, June 28-July 2, 1992.

PMID- 1354012
TI  - Age-related changes in cortico-releasing factor, somatostatin, neuropeptide Y,
      methionine enkephalin and beta-endorphin in specific rat brain areas.
AB  - We investigated the age-related changes in the tissular protein, cortico
      releasing factor (CRF), somatostatin (SOM), neuropeptide Y(NPY), methionine
      enkephalin (M-ENK) and beta-endorphin (beta-END) levels in frontal cortex,
      hippocampus, striatum and hypothalamus of young (4-month-old), mature (18-month
      old) and senescent (26-month-old) Wistar male rats, bred in a specific pathogen
      free environment. Between the age of 4 and 18 months, the tissular protein levels
      increased in all 4 structures studied. The CRF and SOM levels increased in the
      hippocampus, while the NPY levels decreased. During this time, the NPY content
      increased in the striatum, whereas the SOM and M-Enk striatal levels decreased.
      Concomitantly, the NPY and beta-End levels decreased in the hypothalamus.
      Interestingly, no significant variations were found to occur in the frontal
      cortex whatever the neuropeptide studied. Between the age of 18 and 26 months, no
      significant changes in the tissular protein levels were detected, except in the
      hippocampus. The changes in the neuropeptide concentrations observed during this
      period depended on the neuropeptide and the brain structure studied. The CRF and
      beta-End levels decreased in the frontal cortex and the hypothalamus,
      respectively. The NPY peptidergic systems seem to be preferentially affected by
      aging processes since 3 out of the 4 structures studied--the frontal cortex, the
      striatum and the hypothalamus--showed a decrease in their tissular NPY content.
      During the same period, none of the 5 neuropeptides studied were affected in the
      hippocampus.

PMID- 1354016
TI  - Benzodiazepines: tolerance and withdrawal: the clinician's point of view.

PMID- 1354017
TI  - Epidemiology of benzodiazepine dependence.

PMID- 1354018
TI  - Abuse and dependence on the benzodiazepines.

PMID- 1354015
TI  - The pharmacology of benzodiazepine tolerance and withdrawal.

PMID- 1354019
TI  - Human studies of relative abuse liability of benzodiazepines and novel
      sedatives/anxiolytics.

PMID- 1354020
TI  - Benzodiazepines and other psychotropic drugs abused by patients in a methadone
      maintenance program: familiarity and preference.

PMID- 1354021
TI  - Glutamate and anoxic-ischemic cell death in neurons and astrocytes.

PMID- 1354022
TI  - Possible mechanism of sustained neuronal death induced by excessive glutamate and
      endogenous glutamate release; its protection by flunarizine and presence of glia
      cells in cultured cerebellar granule cells.

PMID- 1354023
TI  - Stress, corticotropin-releasing factor neurons, and the actions of
      benzodiazepines.

PMID- 1354024
TI  - Intrinsic activity of DA agonists.

PMID- 1354025
TI  - Interaction of antidepressant drugs with phosphoinositide turnover in human
      platelets and rat brain.

PMID- 1354026
TI  - The expression of neuroreceptor genes and benzodiazepine tolerance.

PMID- 1354028
TI  - Relevance of pharmacokinetic studies on antipsychotics in the management of
      schizophrenic disorders.

PMID- 1354027
TI  - Can brain region-selective dopamine (DA) receptor blockers preferentially act on
      schizophrenia subtypes?

PMID- 1354029
TI  - Bayesian feedback methods for optimising therapy.

PMID- 1354030
TI  - Social isolation and individual differences: behavioural and dopaminergic
      responses to psychomotor stimulants.

PMID- 1354031
TI  - Bromerguride--an ergoline derivative with atypical neuroleptic properties.

PMID- 1354032
TI  - Limbic selective neuroleptics.

PMID- 1354033
TI  - Pharmacological profile of the atypical neuroleptic sertindole.

PMID- 1354034
TI  - Preclinical and clinical properties of the atypical antipsychotic drug
      remoxipride.

PMID- 1354035
TI  - Future directions in antipsychotic drug research.

PMID- 1354036
TI  - Trait-like abnormalities in the sleep of patients with psychoses.

PMID- 1354037
TI  - Colocalization of neuropeptides and classical neurotransmitters--functional
      significance.

PMID- 1354039
TI  - Biochemical and neuropeptide alterations in Alzheimer's disease.

PMID- 1354038
TI  - Somatostatin: a neuropeptide system pathologically altered in Alzheimer's disease
      and depression.

PMID- 1354040
TI  - Benzodiazepines and memory.

PMID- 1354041
TI  - Preclinical and early clinical studies with BW 1370U87, a reversible competitive
      MAO-A inhibitor.

PMID- 1354042
TI  - Mechanism of action of benzodiazepine hypnotics.

PMID- 1354043
TI  - Antidepressants and sleep disorders in affective illness.

PMID- 1354044
TI  - Clinical effectiveness of antidepressants and antipsychotics in chronic benign
      pain.

PMID- 1354045
TI  - Partial allosteric modulation of GABAA receptor: molecular mechanisms and
      clinical implications.

PMID- 1354046
TI  - Alpidem from pharmacology to clinic.

PMID- 1354047
TI  - Abuse liability of bretazenil and other partial agonists.

PMID- 1354048
TI  - The dopamine D3 receptor as a key target for antipsychotics.

PMID- 1354049
TI  - The differential coupling mechanism of dopamine D-2 receptor subtypes: importance
      for the actions of neuroleptic drugs.

PMID- 1354050
TI  - The significance of the D2 dopamine receptor in schizophrenia as studied with
      PET.

PMID- 1354051
TI  - Selective dopamine D-2 receptor antagonists with an atypical neuroleptic profile.

PMID- 1354052
TI  - PET studies of dopamine receptors in relation to antipsychotic drug treatment.

PMID- 1354053
TI  - In vivo assessment of dopaminergic variables in schizophrenia.

PMID- 1354054
TI  - PET studies of drug interaction with brain regional glucose metabolism.

PMID- 1354055
TI  - Neurotransmitters, related circuitry and neuropathology relevant to
      schizophrenia.

PMID- 1354056
TI  - Studies of plasma catecholamine metabolites in acute psychosis.

PMID- 1354057
TI  - Relationship of plasma HVA and treatment response in a large series of patients
      with schizophrenia.

PMID- 1354058
TI  - Measurements of plasma homovanillic acid in schizophrenic patients.

PMID- 1354060
TI  - Evaluation of anxiolytics in normals and patients.

PMID- 1354059
TI  - Usefulness of animal models with newer anxiolytics.

PMID- 1354061
TI  - Clinical efficacy of selective anxiolytic compounds.

PMID- 1354062
TI  - Subtypes of serotonin receptors and anxiolytic drugs: model systems for the study
      of 5-HT receptors.

PMID- 1354064
TI  - A phase-overlapping anhedonia-model (animal-volunteer-patient) to predict the
      effects of neuroleptics.

PMID- 1354063
TI  - Neuroleptics and the ability of animals to experience pleasure.

PMID- 1354065
TI  - Effects of corticosteroids and neurosteroids on sleep EEG.

PMID- 1354066
TI  - Influence of gonadal hormones on neurotransmitters, receptor, cognition and mood.

PMID- 1354067
TI  - Psychometric evaluation of neuroleptics: a review.

PMID- 1354068
TI  - Interaction between aminergic systems in mesolimbic structures: the importance of
      5-HT2, D2 and D1 receptors in the olfactory tubercle for the atypical profile of
      neuroleptics.
AB  - This study shows that the 5-HT2 antagonists ketanserin and ritanserin which on
      top of administration of classical neuroleptics reduces negative symptoms in
      schizophrenia as well as extrapyramidal side effects, are the most potent
      inhibitors of the dopamine-specific responses of the olfactory tubercle (OT);
      like atypical neuroleptics (2), they are far less effective when injected in the
      nucleus accumbens (ACC). We suggest that 5-HT2, D2 and/or D1 antagonism within
      the olfactory tubercle is necessary, but not sufficient for the atypical profile
      of neuroleptics.

PMID- 1354069
TI  - A mixed depressive syndrome.

PMID- 1354070
TI  - Neural substrate of sensitization to psychostimulants.

PMID- 1354071
TI  - PET dopamine D2 receptors and susceptibility to methamphetamine psychosis.

PMID- 1354072
TI  - Differential development of therapeutic drugs for psychosis.

PMID- 1354073
TI  - Pilot studies on the effect of SL 82.0715 in psychotic syndromes.

PMID- 1354075
TI  - Interethnic differences in drug oxidation. Implications for the utilization of
      antidepressants and neuroleptics.

PMID- 1354074
TI  - Conditioned release of neurotransmitters as measured by microdialysis.
AB  - The purpose of this research was to measure conditioned release of
      neurotransmitters in vivo and to study their role as neuromodulators in neural
      circuits controlling food intake. 1. Extracellular serotonin (5HT) was measured
      in the hypothalamus during (a) injection of the anorectic drug d-fenfluramine,
      (b) a normal meal and (c) during the taste of a flavor that previously had been
      paired with nausea. All these situations increased 5HT, suggesting it plays a
      role in suppression of food intake. 2. Extracellular dopamine (DA) in the nucleus
      accumbens (NAC) was released (a) during eating and (b) by a conditioned taste
      associated with intragastric infusion of carbohydrate, but (c) DA decreased in
      response to a taste that had been paired with nausea. Thus some DA projections to
      the NAC may modulate circuits that reinforce eating safe food. Drugs that release
      DA mimic, in part, this safe food effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354076
TI  - Selective inhibition of normal murine myelopoiesis "in vitro" by a Hox 2.3
      antisense oligodeoxynucleotide.
AB  - Multiple homeobox genes are expressed in haematopoietic cell lineages and their
      expression is cell-type specific. Thus we hypothesized that certain homeobox
      genes may play an important role in the process of haematopoiesis. To prove that
      issue, normal murine bone marrow cells were stimulated with appropriate Colony
      Stimulating Factors in the presence of mouse homeobox gene (Hox 2.3) sense or
      antisense oligodeoxynucleotides and the effects on the haematopoietic colony
      formation were examined. Treatment of the cells to Hox 2.3 antisense
      oligodeoxynucleotides led to a selective inhibition of myeloid colony formation,
      both in size and in numbers, but without significant effect on erythroid and
      megakaryocytic haematopoiesis. Exposure to Hox 2.3 sense oligodeoxynucleotides
      (no-oligomers), had no such effect. It was further showed that inhibition of
      myelopoiesis by Hox 2.3 antisense oligodeoxynucleotides was dependent on the
      differentiation stage of target cells. These findings demonstrated that Hox 2.3
      gene plays a critical role in regulating normal murine myelopoiesis.

PMID- 1354077
TI  - Effects of ionophore X-537A on spontaneous transmitter release and the
      ultrastructure of locust neuromuscular junctions.
AB  - The spontaneous quantal release of neurotransmitter and the fine structure of a
      glutamatergic synapse has been examined in the presence of ionophore X-537A. Bath
      applications of X-537A to extensor tibiae nerve-muscle preparations of locust,
      Schistocerca gregaria, increased the frequency of miniature excitatory post
      synaptic potentials (min. e.p.s.p.'s). This action was completely reversible, if
      preparations were exposed to ionophore for less than 60 min. Application of
      ionophore for longer times, i.e., longer than 60 min., transiently elevated min.
      e.p.s.p. frequency to greater than 100/s. Following this period of high activity,
      miniature frequency declined to 0.4/s and were mostly of "giant" miniature
      potentials type. The frequency and amplitude of these "giant" miniature
      potentials remained unchanged after subsequent washing with standard saline.
      Exposure of nerve terminals to ionophore for 60 min. produced no ultrastructure
      changes. Longer ionophore treatments, however, led to depletion of synaptic
      vesicles, damaged mitochondria and disintegration of microtubules and
      neurofilaments within nerve terminals, suggesting irreversible changes at the
      locust neuromuscular junction.

PMID- 1354078
TI  - Cytoskeletal changes accompanying ACTH-induced steroidogenesis in cultured
      embryonic adrenal gland cells from the Pekin duck.
AB  - Cells derived from the adrenal glands of duck embryos immediately prior to
      hatching were grown in culture and used to study the morphological and
      cytoskeletal changes and steroidogenic responses induced by 1-24 ACTH. Changes in
      the cytoskeletal components were observed by rhodamine-phalloidin staining for
      actin and by staining the tubulin immunoreactive components with FITC. The
      cultures were comprised of a small population of chromaffin cells and a larger
      population of steroidogenic cells. The chromaffin cells were distinguished by
      their tyrosine hydroxylase immunoreactivity. The steroidogenic cells were
      characterized by the presence of sudanophilic lipid droplets, numerous
      mitochondria, abundant smooth endoplasmic reticulum, microtubules distributed as
      a fairly even network throughout the cytoplasm, and microfilaments that formed an
      extensive and elaborate system of stress fibers with many parallel arrays. The
      cells readily responded to stimulation with ACTH by releasing corticosterone,
      aldosterone and deoxycorticosterone. Stimulation with ACTH also induced changes
      in both the cell morphology and the cytoskeleton. Exposure of the cells to Krebs
      Henseleit buffer containing 1-24 ACTH caused them to form numerous fine
      filopodia, to lose their stress fibers, and to form a thick ring of actin at the
      periphery of the cell. In addition, many cells became extremely arborized with
      many long branched dendritic processes. The morphological changes appeared to be
      related to a redistribution of the actin components, and may be explained only in
      part by the rounding up or retraction of the cytoplasm. The results strongly
      suggest an involvement of the actin components of the cytoskeleton in the
      steroidogenic response to corticotropic stimulation.

PMID- 1354079
TI  - The alpha 2-adrenergic receptor system in the hypothalamus of the Pekin duck.
AB  - In the present study, we have employed the monoradioiodinated alpha 2-agonist
      clonidine ([125I]-CLO) to characterize duck hypothalamic alpha 2-adrenoceptors
      and to localize alpha 2-specific binding sites in the duck brain. To validate the
      alpha 2-specificity of [125I]-CLO using an enriched duck hypothalamic membrane
      fraction, a radioreceptor assay was established by altering the membrane protein
      concentration, time, temperature and ionic milieu of incubation, and in the
      presence or absence of protease inhibitors. Competitive displacement studies
      revealed the following sequence of potency to displace [125I]-CLO: yohimbine
      greater than (-)-epinephrine greater than clonidine greater than (-)
      norepinephrine greater than phentolamine greater than (-)-phenylephrine greater
      than (-)-isoproterenol greater than prazosin. The non-hydrolyzable guanosine 5'
      triphosphate analog guanylylimidodiphosphate markedly inhibited [125I]-CLO
      binding suggestive of G-protein involvement. With regard to the histological
      distribution, diencephalic structures, such as the habenula and the nucleus
      reticularis of the thalamus, were densely labeled by [125I]-CLO. In the
      hypothalamus, alpha 2-adrenoceptors were detected in the antidiuretic hormone
      synthesizing nucleus paraventricularis, the nucleus praeopticus medialis, the
      nucleus anterior medialis hypothalami, the nucleus magnocellularis praeopticus,
      the nucleus commissurae pallii, the nucleus inferior hypothalami and the regio
      lateralis hypothalami. Circumventricular organs, such as the plexus choroidei,
      organum subfornicale, organum paraventriculare and the corpus pineale, were
      endowed with alpha 2-specific binding sites, as were the cell layers of the
      tectum opticum. In addition, telencephalic structures revealed high receptor
      densities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354080
TI  - Symptomatic angina secondary to coronary-subclavian steal syndrome treated
      successfully by percutaneous transluminal angioplasty of the subclavian artery.
AB  - Subclavian artery stenosis causing severely symptomatic angina in a patient with
      a previous left internal mammary artery bypass to the left anterior descending
      artery was treated successfully with percutaneous transluminal angioplasty.
      Baseline arteriography clearly revealed subclavian and coronary steal by evidence
      of competitive flow of nonopacified blood from the left vertebral artery.
      Although there was a difference of only 15 mm Hg between the right and left
      brachial arteries, there was a palpable difference in the upstroke of these
      pulses. The stenosis in the subclavian artery was successfully dilated with
      percutaneous transluminal angioplasty. Angiographic evidence of subclavian steal
      resolved following balloon dilatation, and the patient's angina was completely
      resolved.

PMID- 1354082
TI  - Possible enhancing effect of the immunosuppressive agent, 6-mercaptopurine(6-MP)
      on focal lesion development in cirrhotic liver induced by carbon tetrachloride
      but not furfural in F344 rats.
AB  - The modifying effects of an immunosuppressive agent, 6-mercaptopurine (6-MP), on
      development of focal lesions in liver cirrhosis models induced by carbon
      tetrachloride (CCl4) or furfural were studied in male F344 rats. Feeding of 6-MP
      at 50 p.p.m. for 20 weeks to animals with pre-existing liver cirrhosis caused
      immunosuppression, and significantly enhanced the induction of gamma
      glutamyltranspeptidase (GGT)-positive foci and nodules in the CCl4 but not
      furfural case. Glutathione S-transferase P (GST-P)-positive preneoplastic lesions
      were not affected. Moreover, phenobarbital (PB) also enhanced the induction of
      GGT-positive hepatocellular lesions only in the CCl4-induced liver cirrhosis
      model, no promotion influence being exerted after treatment with the non
      carcinogenic furfural. This study, therefore, suggests that 6-MP can enhance the
      induction of one type of preneoplastic foci and nodules and that essential
      differences exist between focal lesions arising in cirrhotic livers caused by
      CCl4 as opposed to furfural.

PMID- 1354081
TI  - Chloroform inhibits the development of diethylnitrosamine-initiated,
      phenobarbital-promoted gamma-glutamyltranspeptidase and placental form
      glutathione S-transferase-positive foci in rat liver.
AB  - In this study we demonstrate that chloroform, a widely used industrial solvent, a
      medicinal chemical and a common drinking water contaminant, reduces the number of
      detectable preneoplastic enzyme-altered foci [gamma-glutamyltranspeptidase
      positive (GGT+) and placental form glutathione S-transferase-positive (GST-P+)]
      in the liver of male Fischer 344 rats. The animals were given a partial
      hepatectomy and 18 h later received a single oral dose of either 0.5 mmol/kg
      diethylnitrosamine (DENA) or saline. Two weeks later, groups of 12 animals were
      started on drinking water containing phenobarbital with varying concentrations
      (200-1800 mg/l) of chloroform fro 12 weeks. Treated and control animals were
      killed and the number and the volume of GGT+ and GST-P+ expressing hepatic foci
      were tabulated. The numbers of foci per unit volume (and per unit area), the
      percent focal volume and the focal liver were reduced by chloroform in a dose
      dependent manner. The mean focal volume was not influenced by chloroform. A
      plausible explanation for these results could be that chloroform exerts its focal
      inhibitory effect either by selectively killing the putative initiated cells, by
      retarding the inherent growth rate of enzyme-altered cells or by reducing the
      effectiveness of the promoter, phenobarbital. The available evidence suggests
      that the first hypothesis is the most likely explanation for these observations.
      These results are consistent with earlier studies showing that chloroform
      inhibits tumorigenesis in rodents.

PMID- 1354083
TI  - Characterization of the promotion of altered hepatic foci by 2,3,7,8
      tetrachlorodibenzo-p-dioxin in the female rat.
AB  - Previous studies have suggested that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      acts as a promoting agent in various organ systems including the rat liver. Since
      a major characteristic of the stage of tumor promotion is its operational
      reversibility, we have assessed whether TCDD-induced promotion is reversible in a
      two-stage model of hepatocarcinogenesis. In this model, female Fischer F344 rats
      were administered a single, intragastric dose of the initiating agent,
      diethylnitrosamine (DEN, 10 mg/kg), at the peak of proliferation induced by a
      partial hepatectomy. TCDD was then administered biweekly (0.14 micrograms/kg,
      s.c.) for 1, 3 or 5 months. One group of animals was killed at each of these time
      points, while a second group was maintained for each time point for an additional
      6 months in the absence of further TCDD. Four serial frozen sections of liver
      were each stained with a different enzyme marker of altered hepatic foci (AHF).
      The AHF were identified and the number and volume fraction determined by
      quantitative stereology. Exposure to TCDD resulted in an increase in the number
      and size of AHF in the initiated relative to the uninitiated rats. Increasing the
      duration of promotion with TCDD led to an increase in the number of AHF per
      liver, the volume fraction of the liver occupied by AHF and the number of markers
      expressed aberrantly by a single AHF. Discontinuation of TCDD administration for
      6 months before killing the animals resulted in a decrease in the total number of
      AHF observed, but those AHF that remained increased in size with an overall
      increase in volume fraction of AHF. Analysis of the size class distribution for
      AHF for each of the periods of TCDD promotion revealed an increase in the larger
      AHF but a decrease in the smaller, thereby resulting in an overall decrease in
      number of AHF with an increase in the volume fraction of AHF. Increasing the
      duration of the TCDD exposure prior to its withdrawal led to an increased AHF
      size, phenotypic complexity and number of AHF remaining after cessation of TCDD
      administration. Although the levels of TCDD in livers of rats 6 months after
      cessation of TCDD administration were still greater than background, they were
      markedly reduced compared to immediately after administration. Thus, cessation of
      exposure to TCDD after a brief duration led to a reversal of its promotional
      effects on the majority of AHF, while prolonged exposure led to maintained
      promotion of a minority of AHF.

PMID- 1354084
TI  - A comparison of guanfacine, bunazosin, atenolol and nadolol on blood pressure and
      plasma noradrenaline responses to cold pressor testing.
AB  - 1. The role of the presynaptic adrenoceptor subtypes in man was investigated
      based on observation of the changes in blood pressure (delta BP) and plasma
      noradrenaline concentration (delta NA) with the cold pressor test (CPT). 2. The
      CPT was well reproducible for BP and NA when performed at a 2 week interval in
      patients with mild hypertension. 3. After administration for 4 weeks, guanfacine
      (Gf; alpha 2-adrenoceptor agonist) decreased the delta NA response to CPT. 4.
      After administration for 2 or 4 weeks, bunazosin (Bu; alpha 1-adrenoceptor
      antagonist) atenolol (At; beta 1-adrenoceptor antagonist) and nadolol (Nd; non
      selective beta-adrenoceptor antagonist) did not affect the delta NA response to
      CPT. 5. Both Gf and Bu decreased the systolic blood pressure response (delta SBP)
      to CPT after 4 weeks of the administration. Neither At nor Nd significantly
      changed the delta SBP response to CPT. 6. It is likely that Gf stimulated the
      presynaptic alpha 2 adrenoceptors at the sympathetic nerve endings as well as the
      central alpha 2 adrenoceptors, inhibiting the release of noradrenaline. It is
      unlikely that Bu, At and Nd exerted any clearly defined action on the presynaptic
      adrenoceptors in human hypertensive subjects.

PMID- 1354087
TI  - 4th International Congress of the Metastasis Research Society. Science and
      Medicine in Cancer Metastasis. Paris, France, 31 August-4 September 1992.
      Abstracts.

PMID- 1354085
TI  - Amlodipine combined with beta blockade for chronic angina: results of a
      multicenter, placebo-controlled, randomized double-blind study.
AB  - Amlodipine, a potent long-acting dihydropyridine calcium antagonist, was compared
      with placebo in a parallel, randomized, double-blind study in 134 patients with
      chronic stable angina pectoris maintained on beta-adrenergic blocking agents.
      After a single-blind, two-week placebo period, patients were randomized to
      receive either amlodipine (2.5, 5, and 10 mg) or placebo once daily for four
      weeks. The effects of amlodipine on maximal exercise time, work, time to angina
      onset, and subjective indices including angina frequency, nitroglycerin tablet
      consumption, and patient and investigator ratings were assessed. Each dose of
      amlodipine produced increases in exercise time and calculated total work
      accomplished compared to baseline. Improvements at 5 and 10 mg were significantly
      greater than placebo which produced no significant change (p less than 0.05).
      Qualitative improvements in the severity of angina were produced by amlodipine at
      5 and 10 mg daily assessed by patient-rating questionnaires (p less than 0.05).
      Reductions in angina frequency attacks per week and weekly nitroglycerin tablet
      consumption occurred but were not statistically significant when compared with
      placebo. Adverse effects observed during amlodipine treatment prompted
      discontinuation of treatment in only 2 out of 100 patients. Three patients
      discontinued treatment for reported lack of efficacy. No laboratory abnormalities
      prompted treatment discontinuation and minor side effects of dizziness, nausea,
      headache, and fatigue were observed infrequently. The results of this controlled,
      large-scale multicenter trial suggest that amlodipine significantly increased
      exercise capacity and was well tolerated when added to the antianginal regimen of
      patients remaining symptomatic while receiving beta-blocking agents.

PMID- 1354086
TI  - The effects of beta blockade with (epanolol) and without (atenolol) intrinsic
      sympathomimetic activity in stable angina pectoris. The Visacor Study Group.
AB  - Beta blockade constitutes efficient therapy for stable angina pectoris. The
      effects of lowering blood pressure and heart rate with such treatment are not
      always desired. Epanolol is a beta 1-selective partial agonist with minor effects
      on blood pressure and heart rate at rest. Atenolol is a pure beta 1-selective
      antagonist with more pronounced effects on blood pressure and heart rate at rest.
      The effects of epanolol, 200 mg o.d., and atenolol, 100 mg o.d., were compared in
      173 middle-aged patients with stable angina pectoris in a randomized, double
      blind, parallel group-controlled study for one year. No significant differences
      were shown in angina attack rate, nitrate consumption, or exercise performance.
      Resting heart rate and blood pressure were significantly lower on atenolol.
      Epanolol tended to be better tolerated than atenolol, as shown by visual analogue
      scales of well-being, activity, energy, and warm extremities, further supported
      by fewer reports on possible adverse reactions. In conclusion, epanolol appears
      to be as effective as atenolol and better tolerated in patients with stable
      angina pectoris.

PMID- 1354088
TI  - Prevention of overuse injuries of the foot by improved shoe shock attenuation. A
      randomized prospective study.
AB  - In a randomized prospective study among 390 recruits, the hypothesis that
      improved shoe shock attenuation could lessen the incidence of overuse injuries
      was tested. During the 14 weeks of training, 90% of the recruits sustained
      overuse injuries. Recruits training in a modified basketball shoe had a
      statistically significant lower incidence of metatarsal stress fractures and foot
      overuse injuries, compared with standard infantry boots, but their overall
      incidence of overuse injuries was not reduced. The effect of improved shoe shock
      attenuation was limited to those overuse injuries resulting from vertical impact
      loads.

PMID- 1354089
TI  - Some comparative aspects of drug metabolism in nubian goats (Capra hircus),
      desert sheep (Ovis aries) and dromedary camels (Camelus dromedarius).

PMID- 1354090
TI  - Effects of catecholamines on the isolated aorta of the snake Bothrops jararaca.
AB  - 1. Effects of catecholamines in snakes have been examined using an aorta
      preparation isolated from Bothrops jararaca. Adrenaline, noradrenaline and
      isoprenaline produced dose-dependent contractions on this preparation. The
      relative potency was adrenaline greater than noradrenaline greater than
      isoprenaline. 2. Phentolamine displaced, to the right, the concentration-response
      curve of the three catecholamines tested, showing the presence of alpha
      adrenoceptors in this preparation. 3. Isoprenaline has never produced a
      relaxation, even when the aorta was first contracted by BaCl2 and pretreated with
      phentolamine, indicating that beta-adrenoceptors are absent in this preparation.
      4. In this Bothrops jararaca preparation, exclusively neuronal uptake was found,
      thus demonstrating that its existence was preserved during evolution.

PMID- 1354091
TI  - Hepatic metabolism of artemisinin drugs--III. Induction of hydrogen peroxide
      production in rat liver microsomes by artemisinin drugs.
AB  - 1. In this communication, induction of hydrogen peroxide production by the
      semisynthetic antimalarial drugs of the artemisinin class (beta-arteether, beta
      artelinic acid and dihydroartemisinin) in rat liver microsomes, is reported. 2.
      Endogenous, NADPH-dependent, production of hydrogen peroxide in rat liver
      microsomes was enhanced in the presence of arteether and artelinic acid, but not
      in the presence of dihydroartemisinin. 3. NADPH-dependent metabolism of arteether
      and artelinic acid was closely coupled to the drug-induced production of hydrogen
      peroxide. 4. The redox cycle of cytochrome P-450 was presented, which describes
      satisfactorily both the endogenous and the drug-assisted hydrogen peroxide
      production in rat liver microsomes; also, the rate-limiting step of the cycle was
      identified.

PMID- 1354092
TI  - Effects of copper, cadmium and nickel on liver and kidney glutathione redox cycle
      of rats (Rattus sp.).
AB  - 1. Glutathione redox cycle alterations induced by acute treatment of nickel,
      cadmium and copper, have been investigated in liver and kidney of adult male
      rats. 2. In liver, nickel treatment decreased GSH and GSSG levels, followed by a
      significant rebound in GSH content. Copper produced drastic reduction in the
      GSH/GSSG ratio, while cadmium treatment altered GSSG concentrations. 3. In
      kidney, the glutathione redox cycle remained unaltered after cadmium or nickel
      exposure, whereas copper caused similar changes to those observed in liver. 4.
      Hepatic glucose-6-P dehydrogenase and GSSG-reductase activities decreased after
      copper or nickel injection. GSH-S-transferase activity was altered in various
      ways, depending on the organ and the metal.

PMID- 1354093
TI  - Influx of zinc by channel catfish (Ictalurus punctatus): uptake from external
      environmental solutions.
AB  - 1. Channel catfish (Ictalurus punctatus) take up zinc (measured with 65Zn) from
      external ambient solutions in a concentration dependent manner. At a
      concentration of 10(-6)M Zn, this uptake is equivalent to 0.4% of the total body
      Zn each day. 2. Zinc influx was increased by external acid conditions (decreasing
      pH from 7.3 to 5). 3. Elevated Ca2+ and Cd2+, but not Al3+, concentrations
      markedly decreased the uptake of Zn. 4. These observations may be relevant to
      circumstances that occur under natural conditions, and influence the zinc
      nutrition and toxicity of the fish.

PMID- 1354094
TI  - Catecholamine secretion from adrenal chromaffin cells of the toad (Caudiverbera
      caudiverbera): effect of monensin.
AB  - 1. Stimulus-secretion coupling studies were carried out on adrenal chromaffin
      tissue from the toad. Catecholamine (CA) secretion was generated in response to
      acetylcholine (ACh) or high K+. 2. The response to ACh was found to be dependent
      on the presence of external Ca2+. The secretion induced by ACh or high K+ was
      inhibited by the Ca-channel blockers CoCl2 and nifedipine. 3. The specific Na+/H+
      ionophore, monensin, induced a strong secretory response only if Na+ was present
      in the Ringer. Monensin's effect did not depend on external Ca2+ and was
      unaffected by the channel blockers tetrodotoxin or CoCl2. 4. Secretion induced by
      monensin was exocytotic as was shown by measuring ATP release using a
      photoluminescence, luciferine/luciferase assay. 5. In conclusion, in the toad, as
      in higher species, stimulus-secretion coupling involves Ca2+ entry from the
      external medium, possibly through voltage-dependent channels. Monensin is a
      potent secretagogue and the mechanism by which the ensuing elevation of
      intracellular Na+ concentration might induce a secretory response remains to be
      determined.

PMID- 1354095
TI  - The effects of gamma-aminobutyric acid on voltage-clamped motoneurons of the
      lobster cardiac ganglion.
AB  - 1. We examined the electrophysiological and pharmacological effects of GABA on
      voltage-clamped motoneurons of the lobster cardiac ganglion. 2. GABA caused a
      dose-dependent current (EC50 = 0.7 mM), which reversed at the estimated Cl-
      equilibrium potential. 3. The conductance activated by GABA was voltage
      dependent, increasing as a non-linear function of depolarization. 4. A Na(+)
      dependent GABA uptake mechanism was only weakly sensitive to nipecotic acid. 5.
      Picrotoxin inhibited the GABA response, but bicuculline had no effect. 6. We
      conclude that the effect of GABA in the lobster cardiac ganglion is similar to
      its effect on other crustacean neuromuscular tissues and on vertebrate GABAA
      receptors. 7. There appear to be differences among species with respect to the
      physiology and pharmacology of the Na(+)-dependent GABA transporter. 8. The
      effect of GABA is also similar to the ionic mechanism underlying the action of
      histamine in the cardiac ganglion.

PMID- 1354096
TI  - The in vitro efficacy of reuterin on the culture and bloodstream forms of
      Trypanosoma brucei brucei.
AB  - 1. The in vitro effects of a new antibiotic, reuterin, were determined for
      culture and bloodstream forms of Trypanosoma brucei brucei. It inhibited growth
      of the culture forms and motility, viability and DNA and protein syntheses of
      culture and bloodstream forms. 2. Reuterin administered with inhibitors of
      ribonucleotide reductase (hydroxyurea and deoxyadenosine) was synergistic only
      for growth of the culture form of the parasite. 3. Reuterin was trypanocidal at
      lower doses than DFMO, Mel B, and Suramin and was antagonistic when used with
      these drugs.

PMID- 1354097
TI  - Aflatoxin and glutathione in domestic fowl (Gallus domesticus)--I. Glutathione
      elevation and attenuation by high dietary methionine.
AB  - 1. Changes in hepatic and renal glutathione (GSH) and plasma aspartate
      aminotransferase (AST) following single or daily oral doses of aflatoxin B1
      (AFB1, 2 mg/kg BW) or corn oil vehicle (1 ml/kg BW) were determined in male
      chickens (14-21-day-old). 2. Plasma AST and hepatic GSH increased 2 and 8 hr,
      respectively, following a single AFB1 dose. 3. Hepatic GSH continued to increase
      through 5 daily doses of AFB1, but there were no differences in AST levels on
      days 1-5. Feeding a diet containing 150% of NRC requirement for methionine
      attenuated the AFB1-induced increase in hepatic GSH. Renal GSH was unaffected by
      AFB1 or dietary treatment.

PMID- 1354098
TI  - Mytilus-inhibitory peptide analogues isolated from the ganglia of a pulmonate
      mollusc, Achatina fulica.
AB  - 1. Ten peptides that showed an inhibitory effect on phasic contraction of the
      ABRM of Mytilus were isolated from the ganglia of the African giant snail,
      Achatina fulica. 2. Seven of the peptides were shown to be hexapeptides having 
      Pro-Xaa-Phe-Val-NH2 as a common structure, which was previously shown to be a
      characteristic of Mytilus inhibitory peptides (MIPs). 3. The remaining three were
      pentadecapeptides, each of which consisted of two MIP-related hexapeptides linked
      by -Gly-Arg-Arg-.

PMID- 1354100
TI  - Blood morphology in quails after poisoning with fenitrothion.
AB  - 1. The purpose of this study was to determine changes in the blood of Pharaoh
      quails after fenitrothion intoxication, to define the duration of disturbances
      caused by intoxication and to examine possible sex differences in the birds'
      reaction to intoxication. 2. Fenitrothion reduced the number of erythrocytes,
      haemoglobin level and haematocrit value, but increased erythroblast and
      reticulocyte numbers. 3. Fenitrothion caused neutrophilic leucocytosis with
      lymphopaenia and eosinopaenia. 4. In males, changes in the blood appeared far
      earlier than in females and they underwent compensation earlier, i.e. 3 weeks
      after intoxication the majority of the haematological parameters reached values
      similar to those of the controls.

PMID- 1354099
TI  - Metal redistribution in largemouth bass (Micropterus salmoides) in response to
      restrainment stress and dietary cadmium: role of metallothionein and other metal
      binding proteins.
AB  - 1. Fish stressed by restrainment displayed elevated serum cortisol, copper and
      zinc levels; dietary cadmium had no effect. 2. Stress/dietary cadmium increased
      liver copper levels in a metal pool containing metallothionein and non
      metallothionein proteins but decreased intestinal zinc bound as low molecular
      weight forms. 3. After restrainment, zinc losses occurred in dorsal skeletal
      muscle, ovary and spleen: copper decreased in intestine and pyloric caecum. 4.
      Dietary cadmium altered intestinal zinc distribution and raised hepatic Cu
      binding protein levels but did not alter plasma zinc, copper or cortisol levels.
      5. Alterations in zinc and copper concentrations during stress contrast with
      mammalian models.

PMID- 1354102
TI  - Acute toxicity of ammonia to Atlantic salmon (Salmo salar) parr.
AB  - 1. Atlantic salmon (Salmo salar) parr were exposed to (NH4)2SO4 solutions in
      static systems with aerated, soft water for 96 hr. The 96 hr-LC50 for un-ionized
      ammonia (expressed as mg/l NH3-N) ranged from 0.031 (2.1 degrees C) to 0.111
      (17.1 degrees C) at pH 6.0 and from 0.030 (1.8 degrees C) to 0.146 (12.5 degrees
      C) at pH 6.4. 2. No mortality, was found in a KCl solution and a physiological
      salt solution with chloride concentrations approximately equivalent to the
      chloride concentration in a NH4Cl solution giving 45% mortality, and to the
      ammonia concentration in a (NH4)2SO4 solution giving 35% mortality, all solutions
      tested at pH 6.0 and 2 degrees C.

PMID- 1354101
TI  - Neuropeptide F: primary structure from the tubellarian, Artioposthia triangulata.
AB  - 1. A neuropeptide exhibiting vertebrate pancreatic polypeptide immunoreactivity
      has been isolated and sequenced from extracts of the terrestrial turbellarian,
      Artioposthia triangulata. 2. This neuropeptide, designated neuropeptide F,
      consists of 36 amino acid residues terminating in a phenylalaninamide. 3. The
      full primary structure was established as:
      KVVHLRPRSSFSSEDEYQIYLRNVSKYIQLYGRPRF.NH2. The molecular mass, deduced from this
      sequence, was 4433 Da. 4. This neuropeptide exhibits C-terminal homology with
      neuropeptide F (Moniezia expansa) and with the vertebrate neuropeptide
      Y/pancreatic polypeptide superfamily of which it may represent a phylogenetic
      precursor.

PMID- 1354105
TI  - Furosemide decreases eggshell thickness and inhibits 45Ca2+ uptake by a
      subcellular fraction of eggshell gland mucosa of the domestic fowl.
AB  - 1. Administration of furosemide to egg-laying domestic fowl (single p.o. dose 100
      mg/bird) caused a decrease in the thickness of the shell of eggs laid the next
      day. 2. Furosemide administration in vivo caused a 37% decrease in the uptake of
      45Ca2+ by a subcellular fraction of the eggshell gland mucosa (mainly composed of
      cell fragments and plasma membranes). 3. Furosemide treatment did not affect
      calcium concentrations in plasma or shell gland fluid but did cause a significant
      increase in the calcium concentration in shell gland mucosa. 4. It is concluded
      that the eggshell-thinning effect of furosemide is localized to an inhibitory
      effect on plasma membrane calcium transport in the eggshell gland mucosa. 5.
      These findings are discussed and compared with the effects of other drugs and
      toxic substances known to influence eggshell formation in birds.

PMID- 1354104
TI  - The effects of ethanol on intracellular potassium and the membrane potential of
      an identified crab motor axon.
AB  - 1. Observations were made on the fast bender excitor axon in autotomized crab
      walking limbs bathed in normal crab saline, and in salines made up with 0.2 M
      sucrose or 0.2 M ethanol. Microelectrode techniques were used to measure the
      resting membrane potential and the intracellular level of potassium. 2. Sucrose
      saline had little effect on the membrane potential or the intracellular level of
      potassium. Ethanol-saline hyperpolarized the membrane potential by about 3 mV and
      increased the level of intracellular potassium. 3. The ethanol-induced changes in
      intracellular potassium levels and membrane potential took place with the same
      time course. Further, the changes in membrane potential could be accounted for by
      changes in the equilibrium potential for potassium, Ek as predicted by the Nernst
      equation.

PMID- 1354103
TI  - Involvement of non-classical 5-HT receptor in serotonin and cisapride induced
      secretion in hen colon.
AB  - 1. In hen colon 5-HT induces a tetrodotoxin-resistant, bumetanide-sensitive,
      chloride secretion, positively coupled with adenylate cyclase activity. 2. The 5
      HT receptor mediating this response seems non-classical since it cannot be
      blocked by 5-HT1-like, 5-HT2 or 5-HT3 antagonists. 3. Effects are presented of
      new putative 5-HT agonists and antagonists on short circuit current and cord
      conductance in the hen colon, using the Ussing chamber technique. 4. The
      substituted benzamides, cisapride and BRL 24924, induced a dose-dependent short
      circuit currents but both with less potency than 5-HT. 5. Cisapride mediated this
      dose-dependent bumetanide sensitive response mainly by release of acetylcholine,
      since atropine reduced cisapride response by 70%. 6. Neither BRL 24924, 5-HTP-DP,
      ketanserin, ICS 205-930, prazosin, yohimbine, atropine nor piroxicam, covering
      the 5-HT1P, 5-HT2P, 5-HT2, 5-HT3, 5-HT4, adrenergic and muscarinic receptor types
      and the prostaglandin synthesis, altered 5-HT induced increases in short circuit
      current and cord conductance. 7. Results suggest (a) cisapride mediates it's
      response mainly by releasing acetylcholine, which then stimulates muscarinic
      receptors to release 5-HT. (b) Involvement of a non-classical 5-HT receptor
      subtype in 5-HT induced chloride secretion in hen colon.

PMID- 1354106
TI  - Receptors mediating the actions of 5-hydroxytryptamine on the isolated retractor
      muscle of the penis preparations from Archachatina marginata (Swainson).
AB  - 1. The effects of some 5-hydroxytryptamine (5-HT) receptor agonist and
      antagonists on the isolated retractor muscle of the penis of Archachatina
      marginata were investigated. 2. Both 5-hydroxytryptamine and lysergic acid
      diethylamide (LSD) contracted the preparations. The mean pD2 values obtained for
      5-HT and LSD were 5.26 +/- 0.21 (N = 10) and 6.3 +/- 0.36 (N = 8) respectively.
      3. 5-Methoxy, N,N,-dimethyltryptamine (5-MeODMT; N = 6)
      trifluoromethylphenylpiperazine (TFMPP; N = 6) alpha-methyl 5-hydroxytryptamine
      (alpha-Me-5-HT); N = 6) and both L and DL-5-hydroxytryptophan (L-5-HTP; N = 6, DL
      5-HTP; N = 6) did not contract the preparations even when concentrations up to
      10(-4) M were administered. 4. Ketanserin (10(-8)-10(-6) M) produced rightward
      shift of the concentration-response curve of 5-HT. (pA2 = 8.0 +/- 0.25, slope =
      0.34 +/- 0.03; N = 6). 5. The contractions of the RMP to 5-HT were not
      antagonised by either LY53857 or ICS 205-930. 6. The present study does not
      reveal the presence of 5-HT1-like or 5HT2 receptors on the RMP. However 5-HT3
      receptors do not seem to exist on this invertebrate smooth muscle.

PMID- 1354107
TI  - The most primitive heart in the animal kingdom contains the atrial natriuretic
      peptide hormonal system.
AB  - 1. The newly described atrial natriuretic peptide hormonal system appears to play
      an important role in the endocrine control of sodium and water metabolism in
      human and vertebrate animals, but neither atrial natriuretic factor (ANF, C
      terminal amino acids (a.a.) 99-126 a.a. prohormone) nor the rest of the ANF
      prohormone have ever been demonstrated in the heart of an invertebrate. 2. The
      present investigation was designed to determine whether the earthworm, Lumbricus
      terrestis, the first animal in the phylogenic tree with any form of heart, has
      either ANF and/or the 98 a.a. N-terminus of the ANF prohormone. 3. Both an ANF
      like peptide (189 +/- 32 ng/g of tissue) and the N-terminus of the ANF prohormone
      like peptide (1985 +/- 27 ng/g of tissue) were present in the earthworm heart at
      concentrations significantly higher (P less than 0.001) than in rat (Rattus
      norvegicus) heart ventricles. 4. This newly-described hormonal system, thus,
      appears to be present in a much larger proportion of the animal kingdom than
      previously thought, including invertebrates as well as vertebrates.

PMID- 1354108
TI  - Acute toxicity of ozone against morphology of gill and erythrocytes of Japanese
      charr (Salvelinus leucomaenis).
AB  - 1. Acute toxicity of ozone exposure to Japanese charr (Salvelinus leucomaenis)
      was studied histopathologically, and hematologically on gill tissue and red blood
      cells (RBC) under different ozone concentrations (0-0.7 ppm). 2. Exposure of
      ozone above 0.7 ppm led to characteristic symptoms and all died of choking in 30
      min. 3. Many swollen RBC were seen under the scanning electron microscope. 4. RBC
      congestion was serious in the gill where degeneration of lamellar epithelium was
      observed. However, injury to chloride cells was not clear.

PMID- 1354109
TI  - Binding of the benzodiazepine ligand [3H]-RO 15-1788 to membrane preparations of
      the rabbit and turtle retina.
AB  - 1. We have studied the binding of [3H]-RO 15-1788 to membrane preparations of the
      retina of rabbit (Lepus cunicula) and turtle (Pseudemys scripta elegans). 2. In
      both species, [3H]-RO 15-1788 binding was maximal at 0 degrees C and decreased
      with increasing temperature. It was saturable, protein concentration-dependent
      and specific. Flunitrazepam, unlabelled RO 15-1788 and ethyl-beta-carboline were
      the most effective displacers, whereas RO 5,4864 was ineffective. 3. In both
      turtle and rabbit retina, Scatchard analysis indicated the presence of a single
      binding site for [3H]-RO 15-1788. The KD was 0.75 nM in both turtle and rabbit,
      while the Bmax were 520 and 250 fmol/mg protein in turtle and rabbit
      respectively. A study of the association rate of [3H]-RO 15-1788 binding revealed
      faster kinetics in turtle, as compared to rabbit.

PMID- 1354111
TI  - L-carnitine protects fish against acute ammonia toxicity.
AB  - 1. Juvenile chinook salmon (Oncorhynchus tshawytscha) were injected
      intraperitoneally (i.p.) with 0.25 M mannitol followed 1 hr later by an i.p.
      challenge of ammonium acetate. 2. At 10.75 mmol ammonium acetate/kg body weight,
      98% of the fish showed signs of ammonium toxicity and 69% died. 3. Substitution
      of L-carnitine (10-16 mmol/kg) for mannitol afforded striking protection from the
      subsequent challenge with ammonium acetate; 67% showed no signs of ammonia
      toxicity and only 4% died. 4. Of other quaternary amines tested, trimethylamine
      oxide also afforded protection, but betaine and choline did not.

PMID- 1354110
TI  - Possible site of action of 2-methylserotonin in inducing relaxation of
      acetylcholine-induced contraction in the molluscan (Mytilus edulis) smooth
      muscle.
AB  - 1. The present study investigated the presence of 5-HT3 receptor using 2
      methylserotonin (2-Me-5-HT) in the smooth muscle of Mytilus ABRM. 2. 2-Me-5-HT
      relaxed the acetylcholine-induced contraction in a dose-dependent manner ranging
      from 10(-6) to 3 x 10(-4) M (pD2 = 5.55 +/- 0.32). 3. 2-Me-5-HT-induced
      relaxation was antagonized by 3 x 10(-5) M ketanserin in a competitive manner
      (pA2 = 5.14 +/- 0.1), but not by cypropheptadine, mianserin, MDL 72222 or ICS 205
      930 at a concentration of 3 x 10(-5) M. 4. 2-Me-5-HT (3 x 10(-4) M) did not alter
      the content of cyclic AMP and cyclic GMP in the ABRM. 5. These findings suggested
      that the 2-Me-5-HT-induced relaxation was mediated through 5-HT2-like receptors
      and was not linked to cyclic AMP or GMP systems, and, further, that 5-HT3
      receptor subtype was not present in the ABRM.

PMID- 1354112
TI  - Morphological changes on nerves and histopathological effects on liver and kidney
      of rats by pentachlorophenol (PCP).
AB  - 1. The chronic toxicity of pentachlorophenol (PCP) was studied in rats after 90
      120 days of oral administration ad libitum of 0.3-3 mM PCP aqueous solutions. 2.
      Morphological studies of their sciatic nerves were performed by optical and
      electron microscopy. 3. They showed degenerative changes in about 10% of the A
      and B type of nerve fibers. 4. The myelin sheath was discontinued by complete
      separation in several concentric rings while some other parts of the nerve
      exhibited a variable loss of neurotubules, neurofilaments and other axoplasmic
      components. 5. However, the C type of nerve fibers, the blood vessels and the
      perineurium did not show any morphologic alteration. 6. It was also found that in
      the liver PCP caused hemodynamic vein changes and injury in the hepatocytes such
      as cellular swelling and vacuolar degeneration. 7. The damage in the kidney
      occurred primarily in the glomeruli and secondarily in the proximal tubules
      causing turbid tumefaction and the formation of casts in the tubular lumen.

PMID- 1354114
TI  - Effects of chromium during pH change on blood coagulation in Tilapia sparrmanii
      (Cichlidae).
AB  - 1. Tilapia sparrmanii was exposed to 0.098 mg/l potassium dichromate. 2. The
      effect of chromium on blood coagulation was measured with a thrombelastograph at
      a pH of 5, 7.4 and 9 over 96 hr, as well as an uncontrolled pH after 2 weeks of
      exposure. 3. The prolonged kinetic times and reduced maximal amplitudes at a pH
      of 7, 4 and 9, differed significantly from the control values. 4.
      Thrombelastograms reflected a decrease in the clotting ability of fish blood,
      with an increase in pH, which is typical of thrombocytopenia. 5. It was evident
      that the exposure of fish to chromium led to clotting defects that caused
      internal bleeding.

PMID- 1354113
TI  - Inhibition of the sodium transport by pentachlorophenol (PCP) in toad skin
      (Pleurodema thaul).
AB  - 1. The effects of pentachlorophenol (PCP) were studied in vitro on an active
      ionic transporting epithelium. Ussing's technique was applied on the isolated
      Pleurodema thaul skin. 2. Concentrations of PCP in the range 0.003-0.043 mM
      caused an irreversible dose-dependent inhibition in both the short-circuit
      current and the potential difference. 3. Parameters of an electrical equivalent
      circuit were calculated applying the Isaacon's amiloride test. 4. It was also
      shown that PCP produced a significant increase in the O2 consumption of the skin.
      5. The inhibitory action of PCP on active sodium transport in terms of the
      equivalent electrical circuit and the increased oxygen consumption points to an
      uncoupling action of PCP on the oxidative phosphorylation.

PMID- 1354115
TI  - The effect of hexavalent chromium at different pH values on the haematology of
      Tilapia sparrmanii (Cichlidae).
AB  - 1. The haematology of Tilapia sparrmanii (Smith) was investigated after exposure
      to 0.098 mg.l-1 hexavalent chromium at three different pH values. 2.
      Statistically significant changes occurred between the values of parameters of
      experimental and control fish. 3. At lower pH values erythrocytosis and
      leucocytosis were evident. 4. At an alkaline (9) pH anaemic and leucopenic
      conditions were observed. 5. T. sparrmanii adapted to chronic exposure to
      hexavalent chromium.

PMID- 1354116
TI  - W-7, a calmodulin antagonist, and contracture of malignant hyperthermia
      susceptible skeletal muscle.
AB  - 1. In malignant hyperthermia susceptible muscle fibers, the calmodulin
      antagonist, W-7 (10 microM), evoked contractures and potentiated halothene (3%)
      induced contracture. No effect was seen at 0.1 or 1.0 microM) W-7. 2. Dantrolene
      sodium (6 microM) prevented and reversed W-7 induced contracture: nifedipine did
      not. 3. In chemically skinned fibers, 10 microM, 1.0 microM, and 0.1 microM W-7
      released 100%, 30%, and 10% of stored calcium respectively, and the effect of 10
      microM W-7 was irreversible in that the SR was unable to re-sequestor calcium
      after exposure to the drug. 4. The release of calcium by W-7 was not prevented by
      exogenously added calmodulin (3 microM), nor mimicked by mastoparan (10 microM).
      5. Calcium release by W-7 appears to be independent of calmodulin inhibition.

PMID- 1354117
TI  - Beta 2-adrenergic regulation of urea permeability of the Bufo bufo bladder.
AB  - 1. Isoprenaline strongly increases the urea permeability of the bladder of Bufo
      bufo. This effect is due to its interaction with beta 2-adrenoreceptors,
      activating, in turn, the adenyl cyclase. 2. In order to ensure the regulation of
      urea permeability, the isoprenaline effect is present even in pathophysiological
      conditions, inhibiting the vasopressin action.

PMID- 1354118
TI  - The action of a series of glutamic acid analogues on Helix neuronal glutamate
      receptors.
AB  - 1. Intracellular recordings were made from identified Helix central neurones,
      sensitive to L-glutamate. 2. Out of a range of substituted glutamate analogues,
      only the L- and D-isomers of thio-glutamate possessed clear glutamate-like
      activity. 3. On neurones excited by L-glutamate, the EC50 values for L-glutamate,
      gamma-thio-L-glutamate and gamma-thio-D-glutamate were 30 microM, 20 microM and
      greater than 1 mM, respectively. 4. On neurones inhibited by L-glutamate, the
      EC50 values for L-glutamate, gamma-thio-L-glutamate and gamma-thio-D-glutamate
      were 6.0 microM, 0.7 microM and greater than 200 microM, respectively. 5. It is
      concluded that, unlike the situation with thio derivatives of GABA, thio
      derivatives of glutamate possess potent glutamate-like activity.

PMID- 1354120
TI  - Effects of naloxone on membrane potential of identified neurons of Helix aspersa.
AB  - 1. The action of naloxone, at doses that antagonize the inhibitory actions of
      opioid agonists in mammals, was tested in identified cells of Helix aspersa. 2.
      Naloxone was able to modify the membrane potential of some cells without prior
      exposure to opiate agonists. Some cells were depolarized and others were
      hyperpolarized. 3. Met-enkephalin was also effective in eliciting changes in
      membrane potential of some cells, and failed in others, some of which responded
      to naloxone, and was able to partially antagonize the effect of naloxone. 4. The
      electrophysiological responsiveness of this preparation to opioid agonists and
      antagonists makes this mollusc a suitable model for the study of opioid
      dependence and naloxone pharmacology.

PMID- 1354119
TI  - Comparative assessment of the effect of aflatoxin B1 on hepatic dysfunction in
      some mammalian and avian species.
AB  - 1. Aflatoxin B1 (1.5 mg/kg body weight, i.p.) was administered to rats, mice,
      quail and chickens to examine the comparative effect on hepatic microsomal drug
      metabolizing enzymes, cytosolic glutathione S-transferase and serum enzymes. 2.
      Administration of aflatoxin B1 to rats resulted in a significant decrease in
      microsomal cytochrome P-450, NADPH-cytochrome c reductase, activities of
      aminopyrine N-demethylase, aniline hydroxylase, cytosolic glutathione S
      transferase and liver glutathione content. However, no significant changes in
      these parameters were seen in mice. 3. Quail showed a significant decrease in the
      content of cytochrome P-450 and the activities of aminopyrine N-demethylase,
      aniline hydroxylase and cytosolic glutathione S-transferase. A similar treatment
      did not affect these biotransformation enzymes in chickens. 4. The activities of
      serum enzymes, sorbitol dehydrogenase, alanine aminotransferase and aspartate
      aminotransferase were increased significantly in rats and quail. Mice exhibited a
      significant increase in the activities of sorbitol dehydrogenase and aspartate
      aminotransferase, while chickens showed a significant increase only in alanine
      aminotransferase.

PMID- 1354121
TI  - Effect of Bothrops asper (Fer-De-Lance) snake venom on erythrocyte membrane. A
      comparative study.
AB  - 1. The effect of Bothrops asper venom on erythrocytes of different species, sheep
      erythrocyte ghost vesicles and liposomes made of phospholipids from sheep
      erythrocytes was studied. 2. B. asper venom had a direct hemolytic effect on
      mouse erythrocytes, but no lytic activity on goat, rabbit, horse, toad and sheep
      erythrocytes. Human erythrocytes were lysed only in the presence of bovine serum
      albumin and Ca2+. 3. Although the phospholipase A2 activity in the venom might be
      involved in the lytic effect on mouse erythrocytes, there is also evidence of
      direct lytic factor(s) acting in the absence of calcium ions. 4. Sheep
      erythrocytes were modified in order to study the basis of their resistance.
      Enhancement of membrane fluidity and variation of pH were of no consequence for
      the resistance of sheep erythrocytes to the action of venom. 5. The
      reorganization of membranes that takes place during ghost or liposome preparation
      made them susceptible to B. asper venom-induced disruption. Thus the resistance
      of sheep erythrocytes seems related to the accessibility of the target.

PMID- 1354122
TI  - Aflatoxin and glutathione in domestic fowl (Gallus domesticus)--II. Effects on
      hepatic blood flow.
AB  - 1. The effect of aflatoxin on plasma aspartate aminotransferase (AST), protein,
      and hepatic glutathione (GSH) and hepatic blood flow (perfusion), were determined
      in 3-week-old male chickens. 2. Daily aflatoxin gavage (2 mg/kg body wt, in corn
      oil) for 5 and 10 days elevated plasma AST and hepatic GSH, and depressed plasma
      protein and hepatic perfusion. Also, renal GSH was elevated after 10 days of
      aflatoxin treatment. 3. Birds given aflatoxin for 10 days followed by a 10-day
      recovery period exhibited tissue GSH, plasma AST and protein levels that were not
      different from control, but hepatic perfusion remained depressed.

PMID- 1354123
TI  - Identification of a novel 5-HTN (Nematoda) receptor from Ascaris suum muscle.
AB  - 1. The abilities of various serotonergic drugs to bind with the 5-HT receptor of
      Ascaris suum muscle and to affect cyclic AMP levels in muscle tissue were
      examined. 2. Ligands which selectively interact with either the 5-HT1 or the 5
      HT2 receptor in mammalian systems interact with the 5-HT receptor from A. suum
      muscle and increase cyclic AMP levels. 3. No binding of 5-HT3 ligands to 5-HT
      receptors from A. suum muscle was observed. 4. The 5-HT receptor of A. suum
      muscle should be called the 5-HTN (for Nematoda) receptor because its
      pharmacological and biochemical behaviors were different from those of mammalian
      5-HT receptors.

PMID- 1354124
TI  - Combined effect of fascioliasis and diethylnitrosamine carcinogenesis on the
      activity of the rat liver monooxygenase system.
AB  - 1. The activity of the rat liver monooxygenase system after single and combined
      treatment with Fasciola hepatica and diethylnitrosamine (DENA) has been studied
      in a 27-week experiment. 2. The changes in lever drug metabolism were due mainly
      to F. hepatica with DENA having a modulating effect only. 3. The results are
      discussed with reference to earlier data of ours concerning the effects of
      stimulation or inhibition of DENA-induced liver carcinogenesis against a
      background of acute or chronic fascioliasis.

PMID- 1354125
TI  - Quantitative characterization of beta-adrenergic receptor subtypes in porcine
      adipocytes.
AB  - 1. Two populations of beta-adrenergic receptor (beta AR) subtypes and their
      proportions were characterized in adipocytes isolated from subcutaneous adipose
      tissue of castrated male crossbred pigs (60-85 kg). 2. Specific binding of the
      radioligand 125I-iodopindolol (IPIN) to crude plasma membranes (70-90% of total
      binding) reached equilibrium conditions in 30 min (38 degrees C), was tissue
      concentration-dependent, stereospecific and saturable (bmax = 168 +/- 5.8 fmol/mg
      protein). 3. Displacement curves by ICI 89,406 were best-fit by a two site model
      (P less than 0.01) that indicated the presence of two receptor populations and
      selectivity of IPIN for the beta 2AR subtype. 4. Forty-five percent of the
      receptors had a high affinity for ICI 89,406, Ki = 2.27 +/- 0.68 nM and were
      classified as beta 1AR.

PMID- 1354127
TI  - Serotonin-immunoreactive neurons in the ventral nerve cord of the larva of the
      Eastern spruce budworm, Choristoneura fumiferana.
AB  - 1. Using indirect immunofluorescent method, the distribution of serotonin
      immunoreactivity was examined in the ventral nerve cord of the larva of the
      Eastern spruce budworm, Choristoneura fumiferana. 2. There were two pairs of
      serially homologous serotonin immunoreactive neurons per ganglion. 3. The
      subesophageal ganglion which develops from the fusion of three neuromeres had
      accordingly, six pairs of immunoreactive neurons. 4. The neurons were positioned
      ventrolaterally at the posterior end of the ganglia and distributed in a
      bilaterally symmetrical fashion. 5. The axonal processes from serotonin
      immunoreactive neurons projected to the contralateral side of the hemiganglion
      through a ventral commissure and formed an extensive network of fibers on the
      dorsal side of each ganglion.

PMID- 1354126
TI  - Ethanol-inducible microsomal aniline hydroxylase activity and cytochrome P-450
      isozymes in adult hen liver.
AB  - 1. Cytochrome P-450 was induced in adult hen liver by administering 15% ethanol
      in drinking water and compared with other inducers such as phenobarbital and beta
      naphthoflavone. 2. Aniline was the only substrate whose turnover was induced by
      ethanol treatment when measured in the presence of 100 microM alpha
      naphthoflavone. 3. The inhibitor alpha-naphthoflavone differentiated aniline and
      p-nitrophenol hydroxylase activities, while p-hydroxyphenyl imidazole and SKF
      differentiated p-nitrophenol hydroxylase activity between ethanol- and beta
      naphthoflavone-induced microsomes. 4. Ethanol treatment also slightly induced
      some P-450 isozymes related to phenobarbital and beta-naphthoflavone inducers.

PMID- 1354128
TI  - Impact of cadmium on the mummichog Fundulus heteroclitus and the role of calcium
      in suppressing heavy metal toxicity.
AB  - 1. Freshwater adapted mummichogs (Fundulus heteroclitus) were exposed to cadmium.
      In soft water (less than or equal to 5 mg/l CaCO3), the 4-day safe (TL100) and
      sublethal (TL50) tolerance limits (TLs) for cadmium were 0.14 microgram/l and
      12.2 micrograms/l, respectively. 2. Survival declined with increasing cadmium
      concentration and the length of exposure. The toxicity of cadmium was reduced in
      water with high calcium concentration (200 mg/l CaCO3). Pre-exposure to calcium
      also prolonged the survival in cadmium-containing water. 3. The mummichog appears
      to be extremely well suited for monitoring environmental cadmium poisoning.

PMID- 1354130
TI  - Chelating agent reversal of cadmium effects on ionic transport in the isolated
      frog skin (Rana temporaria).
AB  - 1. The application of 1 mM CdCl2 to the outside surface of frog skin causes a
      large increase in the potential difference (PD) across the skin and in the short
      circuit current (SCC); the subsequent addition of selected dithiocarbamate
      chelating agents (which by themselves have no effect on PD or SCC) restored both
      electrical parameters to values close to initial levels. 2. The response observed
      on addition of the chelating agents indicates that the effect of CdCl2 is
      reversible and that the complexed ions do not possess the ability to initiate
      corresponding changes in the transepithelial ion transport processes in the frog
      skin.

PMID- 1354129
TI  - Physiological properties of liver, gonads and muscle during maturation of female
      Atlantic salmon, Salmo salar. Comparison between a control and xenobiotics
      containing fish feed.
AB  - 1. Atlantic salmon, Salmo salar, in their 4th year were maintained in a sea-based
      farm in the Baltic Sea, salinity 0.2-0.4%. The fish were fed a control diet or a
      diet containing, among the lipid-soluble xenobiotics, 60 parts of dioxin per
      10(12) parts of fish oil. 2. In the fish that attained sexual maturity the liver
      and gonadal wet weight increased, but decreased after stripping of the roe.
      Vitellogenesis was also apparent as an elevated level of plasma vitellogenin
      which was higher after than 2 months prior to removal of the roe. 3. In muscle
      protein content was highest prior to the removal of the roe. RNA content
      decreased with time. Following the taking of the roe glycogen content and acid
      proteinase activity were elevated. 4. Comparison between the feeding groups
      showed, in the fish fed the experimental diet, a higher gonadal wet weight and
      plasma vitellogenin content, and in muscle, after stripping of the roe, a lower
      glycogen content and an elevated level of acid proteinase activity.

PMID- 1354131
TI  - Effects of pressure and gaseous anesthetics on the aggregation of human blood
      platelets and marine sponge cells: similarities in responses.
AB  - 1. Aggregation of blood platelets and marine sponge cells was inhibited by
      nitrous oxide (N2O) and helium (He) at elevated pressure but potentiated by xenon
      (Xe) despite the fact that Xe and N2O are equipotent gaseous anesthetics. 2. The
      above aggregations are dependent on an extracellular source of calcium. 3.
      Platelet aggregation induced by phorbol myristate is independent of extracellular
      calcium and was inhibited by both N2O and Xe and by high pressures of He. 4. The
      results argue against a common mechanism for Xe and N2O and suggest that pressure
      may affect calcium interactions with binding site.

PMID- 1354132
TI  - The effects of clonidine and three 2-imidazoline derivatives on the secretion of
      protein and some electrolytes by rat submandibular and parotid glands.
AB  - 1. Three imidazoline analogues of clonidine were potent secretagogues for the
      parotid and submandibular glands at relatively high doses. 2. Salivation in
      response to clonidine was completely abolished by prazosin, phentolamine,
      phenoxybenzamine and dihydroergotamine. 3. The gamma-type of proteins was
      secreted in response to three of the analogues, whereas with p-aminoclonidine the
      alpha-type of proteins was secreted by the submandibular gland. 4. Albumin was
      specifically secreted by the submandibular gland in response to clonidine but not
      to isoproterenol or phenylephrine.

PMID- 1354133
TI  - Phase-shifting of a neuronal circadian pacemaker in Bulla gouldiana by
      pentylenetetrazol.
AB  - 1. The convulsant agent pentylenetetrazol generates compound action potential
      activity from the circadian pacemaker cells in the Bulla retina. 2. The phase
      response curve to 3 hr pulses of pentylenetetrazol consists of only phase delays
      which occur following pulses delivered in the early subjective night. 3. Phase
      shifts to pentylenetetrazol are independent of extracellular calcium since they
      persist in a low-calcium EGTA solution.

PMID- 1354134
TI  - The autonomic innervation of the large intestine of the toad (Bufo marinus).
AB  - 1. A study was made of the pelvic and the splanchnic nerve supplies to the toad
      large intestine. 2. Stimulation of pelvic nerve fibres in the 9th and 10th spinal
      nerves caused a series of contractions of the circular muscle, only the first of
      which was abolished by hyoscine. The entire response was blocked by d
      tubocurarine. The response was not affected by capsaicin treatment. 3.
      Stimulation of the splanchnic nerves caused a rapid contraction followed by a
      prolonged relaxation. The relaxation was abolished by bretylium. The contraction
      was selectively antagonised by prolonged exposure to capsaicin. Splanchnic nerve
      stimulation also caused a slow, prolonged excitation that was abolished by
      bretylium. 4. Application of adrenaline caused relaxation of circularly cut
      strips of large intestinal wall, whereas substance P, acetylcholine, 5
      hydroxytryptamine, somatostatin and galanin caused contraction. 5. The results
      suggest that stimulation of the pelvic nerves releases acetylcholine and a non
      cholinergic co-transmitter from peripheral postganglionic neurons. Both the
      inhibitory response to splanchnic nerve stimulation and the subsequent slow
      excitation appear to be mediated by adrenergic nerves. The rapid capsaicin
      sensitive excitation is likely to be due to release of substance P from
      antidromically activated afferent nerve fibres in the splanchnic outflow.

PMID- 1354135
TI  - Induction of cadmium tolerance in two clones of Daphnia magna straus.
AB  - 1. The abilities of two different genotypes of Daphnia magna to develop cadmium
      resistance through physiological adaptation, after pre-exposure to sublethal
      concentrations of Cd, Zn and Cd/Zn mixtures, was investigated. 2. The induced
      elevation in cadmium tolerance was shown to be associated with an increase in the
      body concentration of metallothionein-like proteins. 3. The highly significant
      difference in acute responses to cadmium between the two clones reduced after pre
      exposure. 4. Differences in cadmium tolerance were shown to be associated with
      differences in cadmium uptake.

PMID- 1354136
TI  - Effects of a benzodiazepine on the muscle membrane architecture of the rat
      diaphragm. A freeze-fracture study.
AB  - 1. Midazolam increases, stimulation-independently, the amount of intermembraneous
      particles on the sarcolemma of the muscle fibres of the diaphragm. 2. Midazolam
      does not affect the amount of orthogonal arrays of particles on the sarcolemma.
      3. Possible mechanisms for the action of midazolam are discussed.

PMID- 1354137
TI  - Penetration, excretion and metabolism of 14C malathion in susceptible and
      resistant strains of Plutella xylostella.
AB  - 1. The rate of penetration 14C malathion into the larvae of the diamondback moth,
      Plutella xylostella L., was found to be significantly different in an R-strain
      and S-strain. The rate of penetration was more rapid in the R-strain during the
      first hour after treatment. 2. The rate of metabolism in vivo and the rate of
      excretion were also higher in the R-strain compared with the S-strain. 3. The
      main metabolites produced in both strains were malathion dicarboxylic acid and
      desmethyl malathion. 4. The mechanism of insecticide resistance in Plutella
      xylostella L. is multifactorial, and involves a higher rate of penetration into
      the larvae of the R-strain, a higher activity of enzymes involved in its
      metabolism, and a higher level of excretion of the toxic compounds from the body
      of the R-strain compared with the S-strain.

PMID- 1354138
TI  - Influence of the nutritional state of Triatoma infestans over the insecticidal
      activity of DDT.
AB  - 1. The influence of nutritional state over topical insecticidal activity of DDT
      in nymph II of Triatoma infestans was analyzed. 2. DDT LD50 for starved nymph II
      was more than 150 micrograms/insect, while for nymph II fed to repletion on
      artificial feeder, was 0.79(0.50-3.13) micrograms/insect and a similar result was
      obtained for nymph II fed on pigeons (1.09(0.36-7.55) micrograms/insect). 3. A
      very slow penetration rate of 14C-DDT was obtained in non fed insects (4.4%
      penetrated 46 hr after treatment) in correspondence with 0% of mortality. 8.5% of
      14C-DDT was not recovered from the cuticle 2 hr after topication of fed nymph in
      correspondence with a 100% of mortality at 24 hr.

PMID- 1354139
TI  - The dynamics of MS-222 anaesthesia in a marine teleost (Pagrus auratus:
      Sparidae).
AB  - 1. MS-222 anaesthesia of the marine teleost Pagrus auratus caused a dose
      dependent elevation in haematocrit. 2. At 60 mg/l MS-222 the elevated haematocrit
      was fully accounted for by erythrocyte swelling, but at 100 mg/l red cell count
      also increased. 3. Uptake of anaesthetic in all tissues was rapid and the rate of
      onset of anaesthesia was dose-dependent. 4. Stage III level of anaesthesia (loss
      of equilibrium) was correlated with critical levels of MS-222 in the blood and
      brain. 5. The presence of acetylated derivatives of MS-222 in the blood
      demonstrated degradation of the anaesthetic, and high levels in the liver and
      kidney suggested that these organs were the sites of drug metabolism.

PMID- 1354140
TI  - Isolation and characterization of a Cd-binding protein from Allolobophora
      caliginosa (Annelida, Oligochaeta): distinction from metallothioneins.
AB  - 1. One Cd-binding peak was detected after gel filtration chromatography on
      Sephadex G75 in an extract from Allolobophora caliginosa contaminated with Cd. 2.
      Two subsequent cation-exchange chromatographies allowed the isolation of a Cd
      binding protein which was called Cd-BP14. This protein is a monomer with a
      molecular weight of 14 kDa and has an isoelectric point of 6.5. 3. Amino acid
      analysis showed the presence of a high level of aromatic amino acids and a lack
      of cysteine. 4. On the basis of these results we conclude that Cd-BP14 is
      different from metallothioneins described in mammals or other invertebrates.

PMID- 1354141
TI  - Reductive biotransformation of xenobiotics by the sheep ruminal content.
AB  - 1. Sheep ruminal content was able to reduce nitro groups from nitrobenzene and
      azo groups from dimethylamino-azobenzene. 2. Results might be of interest in
      relation to ruminants exposed to environmental chemicals via oral route. 3.
      Biotransformation of xenobiotics in rumen might give to deleterious products
      appearing later in meat and/or milk or harming the ruminant itself.

PMID- 1354142
TI  - Comparison of cadmium, mercury and calcium accumulations by isolated hepatocytes
      of the small skate (Raja erinacea) and rat.
AB  - 1. Accumulation of calcium, cadmium and mercury by isolated hepatocytes of the
      small skate (Raja erinacea) and rat was examined at 14 and 37 degrees C,
      respectively. 2. Metal uptakes by both species were biphasic, with rat cells
      accumulating more metal than the skate cells. 3. Total accumulation after 30 min
      was in the order: mercury = cadmium much greater than calcium. 4. In both species
      calcium and cadmium accumulations were reduced at 4 degrees C, while mercury
      accumulation was not. 5. Cd accumulation was increased by Cu and Hg in both
      species. 6. Hg accumulation was inhibited by Cu in both species, and increased by
      Cd only in the rat cells.

PMID- 1354143
TI  - Differential haemotoxic effect of PCB congeners in the common shrimp, Crangon
      crangon.
AB  - 1. Specimens of the common shrimp, Crangon crangon, were exposed to sub-acute
      logarithmically separated concentrations (ranging from 0.05 microgram to 500
      micrograms l-1) of two structurally dissimilar PCB congeners (PCB 15 and PCB 77)
      for five days in vitro. 2. Mortality, recoverable haemolymph volume, haemocyte
      count, plasma protein and haemolymph osmolarity were determined for test animals
      together with levels of haemolymph cell prophenoloxidase, an indicator of immune
      potential. 3. Sub-acute concentrations of PCB 15, but not PCB 77, produced
      significant decreases in haemocyte count and phenoloxidase activity with a marked
      increase in recoverable haemolymph volume. 4. No effect was observed on
      haemolymph osmolarity or plasma protein levels with either PCB 77 or PCB 15.

PMID- 1354144
TI  - Bioconcentration of atrazine in the banded tilapia, Tilapia sparrmanii.
AB  - 1. The bioconcentration of atrazine was determined in the liver, muscle, heart,
      gonads and brain of Tilapia sparrmanii exposed to high concentrations of
      atrazine. 2. The highest concentrations were recorded in the ovaries (50.6
      micrograms/g) and in the liver (40.1 +/- 5.5 micrograms/g). This may be
      attributed to the higher lipid content of these organs, while the liver also
      accumulates atrazine as a result of its detoxification function. 3. The
      bioaccumulation factors for atrazine in the liver, muscle, heart, gonads and
      brain ranged from 0.9 to 20.0. Bioconcentration of atrazine in banded tilapia was
      found to be low, even after exposure to external atrazine concentration much
      higher than detected in natural surface water.

PMID- 1354146
TI  - The metabolism of noradrenaline in the sheep and the effect of dry matter intake
      upon the production of a metabolite, urinary vanillylmandelic acid.
AB  - 1. The metabolism of noradrenaline was investigated in the sheep using 3H
      noradrenaline injected subcutaneously or intravenously. 2. Analysis of urine
      collected over 24 hr showed that the bulk of 3H-noradrenaline was rapidly
      degraded and excreted via the urine. The principle metabolite was the conjugated
      amine as well as monohydroxy phenyl glycol and vanillylmandelic acid (VMA)
      previously reported for the rat. 3. Urinary VMA from lambs of two breeds noted
      for differences in fat (Southdown and Suffolk) increased curvilinearly with dry
      matter intake and there was a significant breed difference in regression with
      intake. 4. It is feasible that differences in noradrenaline production could
      contribute to differences in body composition between breeds.

PMID- 1354145
TI  - L-sorbose does not cause hemolysis in dog erythrocytes with inherited high Na, K
      ATPase activity.
AB  - 1. The hemolytic effect of L-sorbose on canine erythrocytes characterized by
      inherited high Na, K-ATPase activity and a high potassium concentration (HK RBCs)
      was compared with that on normal canine erythrocytes (LK RBCs). 2. Dogs having HK
      RBCs (HK dogs) revealed no clinical and hematological changes after
      administration of L-sorbose, whereas normal dogs (LK dogs) developed severe
      hemolytic anemia associated with hemoglobinuria and marked decreases of
      erythrocyte ATP concentrations. 3. In vitro, L-sorbose induced hemolysis in LK
      RBCs along with the depression of both ATP and lactate formation in these cells,
      but not in HK RBCs. The inhibition of glycolysis by L-sorbose in LK RBCs,
      however, was not observed when glucose-6-phosphate was used as a substrate
      instead of glucose. 4. These results suggest that the disparity of susceptibility
      to sorbose-induced hemolysis may be due to the difference in erythrocyte
      metabolism between HK and LK RBCs, especially the high activity of hexokinase in
      HK cells, which was 2-fold greater than that in LK RBCs.

PMID- 1354147
TI  - Duck lymphocytes--V. Transformation responses to phorbol ester and calcium
      ionophore.
AB  - 1. Lymphocytes purified from duck blood and spleen were cultured in the presence
      of phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187.
      Stimulation was assessed by the incorporation of [3H]thymidine after 3 days'
      culture. 2. PMA stimulated over a wide range of concentrations, with maximum
      stimulation at final concentrations of 5 x 10(-7)-5 x 10(-8) M/litre. A23187 was
      effective in the range 5 x 10(-6)-5 x 10(-7) M/litre and also, in some
      experiments using spleen lymphocytes, at 5 x 10(-11)-5 x 10(-12) M/litre. 3.
      Synergism was observed between PMA and A23187, the pattern depending on the
      concentrations of these reagents employed. Synergism was also observed between
      PMA and suboptimum concentrations of phytohaemagglutinin (PHA), wheat germ
      agglutinin (WGA), pokeweed mitogen (PWM) and Bandeiraea simplicifolia seed
      extract (BSS), but not with concanavalin A (Con A), lentil lectin (LL) or Helix
      pomatia lectin (HP). Similarly, synergism occurred between A23187 and WGA or PWM,
      but not with PHA, BSS, Con A, LL or HP. 4. Mitomycin C and cycloheximide
      inhibited the response of duck lymphocytes to PMA, A23187 and lectins.
      Cyclosporin A inhibited responses to lectins but not to PMA or A23187. Neither
      hydrocortisone nor indomethacin inhibited responses to lectins, PMA or A23187. 5.
      These results indicate that activation of duck lymphocytes occurs by virtue of
      similar intracellular messenger pathways to those operating in mammalian
      lymphocytes.

PMID- 1354148
TI  - Chaperones and matchmakers: inhibitors and stimulators of protein
      phosphorylation.

PMID- 1354149
TI  - Molecular studies on trypanothione reductase: an antiparasitic target enzyme.

PMID- 1354150
TI  - Systematic desensitization of oral hypersensitivity in a patient with a closed
      head injury.
AB  - A 36-year-old man who had sustained a closed head injury displayed extreme fear
      of being stimulated in the oral cavity, of being presented with foods, and of
      swallowing. The patient's fear increased his muscle tone and hypersensitivity in
      the facial and oral area, thereby preventing assessment of his dysphagia. We
      describe the use of systematic desensitization to alleviate the patient's fear
      thus allowing successful completion of a videofluoroscopic barium swallow
      examination.

PMID- 1354151
TI  - [The bactericidal efficiency of ultrasonic in the root canal].
AB  - The objective of this paper was to determine the quantitative bactericidal
      efficiency of ultrasonic in the root canal. Four test organisms found frequently
      in the root canal were compared. The result showed ultrasonic can kill the test
      organisms effectively in the root canals. The best bactericidal efficiency
      occurred at 4 or 5 min. of ultrasonic though the more efficiency as the time
      longer. Bactericidal irrigation could increase the bactericidal efficiency of
      ultrasonic and its bactericidal action similar to irrigation bactericidal
      property.

PMID- 1354152
TI  - [Advances in clinical treatment of anxiety disorders].

PMID- 1354153
TI  - [Immediate effect and family history of the type I, II schizophrenia].
AB  - 34 cases of the type I Schizophrenia and 30 cases of the type II schizophrenia
      had been studied in immediate effect and family history. Symptomatic changes were
      tested by SANS and SAPS. The results showed that type I group was more cases of
      prominent effect and social function revival, less the time of prominent effect,
      less meam daily in hospital, less the time of happening psychosis disease and the
      positive family history than the type II group. (P less than 0.005, P less than
      0.05). But no statistical significance in comparison of the all-dose of
      antipsychotic drugs between the two groups (P greater than 0.05).

PMID- 1354154
TI  - H2-receptor antagonist nonresponders and omeprazole.

PMID- 1354155
TI  - Zollinger-Ellison syndrome, antisecretory treatment, and body weight.

PMID- 1354156
TI  - [New therapy attempts in duodenal and stomach ulcers].

PMID- 1354157
TI  - Urinary and serum gamma glutamyl transpeptidase in relation to urinary pH and
      proteinuria in healthy thoroughbred horses in training.

PMID- 1354158
TI  - Defective monocyte oxidative metabolism in a child with Smith-Lemli-Opitz
      syndrome.
AB  - We present a patient with Smith-Lemli-Opitz syndrome with immunodeficiency. The
      patient suffered numerous infectious episodes, atopic dermatitis and wheezing.
      Immunological investigations demonstrated severely reduced oxidative burst
      responsiveness of the blood monocytes, whereas chemotaxis, phagocytosis and
      interleukin-1 production were normal. Tests of neutrophils and lymphocytes were
      normal excluding previously described immune deficiency disorders. The father
      proved to have diminished monocyte oxidative metabolism as well, whereas the
      mother had normal monocyte function. The genetic and immunological aspects are
      discussed in relation to the syndrome.

PMID- 1354159
TI  - The value of laparoscopy in the management of the impalpable cryptorchid testis.
AB  - From January 1981 till October 1991, 47 diagnostic laparoscopies were performed
      in 50 impalpable testicles. In total, 28 intra-abdominal testes were found. In 14
      cases no testes were found, but a deferential duct and vessels were seen. In 7
      cases the diagnosis of testicular agenesia was made. One laparoscopy was a
      technical failure. We bring our results of this safe and reliable procedure, and
      discuss our management. A review of treatment options for intra-abdominal testes
      is given.

PMID- 1354160
TI  - Central obesity and hyperinsulinaemia in women are associated with polymorphism
      in the 5' flanking region of the human insulin gene.
AB  - Obesity is a multifactorial disease with a marked genetic component. The
      situation is further complicated by the heterogeneity of obesity demonstrated by
      the topographical distribution of body fat, e.g. upper body (central) and lower
      body (gluteal) obesity. Furthermore, the distribution of fat shows a stronger
      heritable tendency compared with total body fat. Central obesity is characterized
      by hyperinsulinaemia and insulin resistance, a feature in common with non-insulin
      dependent diabetes mellitus, hypertension and atherosclerosis. In order to study
      the molecular genetics of central obesity we have examined 56 severely obese
      (mean body mass index 40), unrelated British Caucasoid young non-diabetic women
      for associations of restriction fragment length polymorphism of candidate genes
      with anthropometric measurements and indices of insulin secretion and resistance.
      The candidate genes examined were insulin receptor, insulin sensitive glucose
      transporter and insulin. An association of the class 3 allele of the
      hypervariable region in the 5' flanking region of the insulin gene was found with
      upper segment obesity (P = 0.005). Furthermore, the class 3 allele was also
      associated with fasting hyperinsulinaemia (P = 0.01), stimulated insulin
      secretion (P = 0.01) and insulin resistance as calculated from the homeostatic
      model of assessment (HOMA; P = 0.008). No such associations were found with the
      other candidate genes studied. This data suggests that polymorphisms in the 5'
      flanking region of the insulin gene may affect expression of the gene and thereby
      modulate insulin production in severely obese female subjects.

PMID- 1354161
TI  - Combination of a delta opioid receptor agonist but not a mu opioid receptor
      agonist with the D1-selective dopamine receptor agonist SKF 38393 markedly
      potentiates different behaviors in mice.
AB  - The effects of intracerebroventricular injections of opioid peptides selective
      for mu or delta opioid receptors on behaviors induced by the D1 dopamine agonist
      SKF 38393 were investigated by using multi-dimensional behavioral analyses. A
      10.0 mg/kg dose of SKF 38393 produced a marked increase in grooming behavior. The
      SKF 38393 (10.0 mg/kg)-induced increase in grooming behavior was clearly
      antagonized by SCH 23390 (0.03 mg/kg), a D1 dopamine antagonist, but not by S(-)
      sulpiride (10.0 mg/kg), a D2 dopamine antagonist. [D-Ala2,MePhe4,Gly5
      ol]enkephalin (DAMGO) (0.003 and 0.01 microgram), a mu-selective agonist, or [D
      Pen2,L-Pen5]enkephalin (DPLPE) (0.3 or 1.0 microgram), a delta-selective agonist,
      failed to affect spontaneous behaviors. The combination of DPLPE (0.3 and 1.0
      microgram) but not of DAMGO (0.003 and 0.01 microgram) with SKF 38393 (10.0
      mg/kg) produced a marked increase in linear locomotion and circuling away from
      the side receiving the peptide, whereas grooming behavior was not affected. The
      effects induced by DPLPE (1.0 microgram) plus SKF 38393 (10.0 mg/kg) were fully
      reversed by the delta-selective opioid antagonist naltrindole (10.0 mg/kg), SCH
      23390 (0.03 mg/kg) and S(-)-sulpiride (10.0 mg/kg). These findings suggest that
      delta but not mu opioid systems interact with D1 dopamine receptors, resulting in
      a marked increase in linear locomotion and contralateral circuling without
      causing marked changes in grooming behavior.

PMID- 1354162
TI  - An inhibitory effect of isoprenaline on stimulation-induced noradrenaline release
      from rat atria.
AB  - Isoprenaline (0.1 microM), in the presence of phentolamine (1 microM) to block
      autoinhibitory alpha-adrenoceptors, significantly increased the efflux of
      radioactivity produced by field stimulation (2 Hz for 60 s) from rat isolated
      atria in which the noradrenergic transmitter stores had been labelled with
      [3H]noradrenaline. This facilitatory effect of isoprenaline on noradrenergic
      transmission was not affected by the selective beta 1-adrenoceptor antagonist CGP
      20712A (0.3 microM). However, the selective beta 2-adrenoceptor antagonist ICI
      118551 (0.1 microM) not only abolished the facilitatory effect of isoprenaline
      but reversed it to an inhibitory effect, indicating that the prejunctional beta
      adrenoceptors subserving facilitation of noradrenergic transmission in rat atria
      are of the beta 2-subtype. The inhibitory effect of isoprenaline that was
      revealed by blockade of beta 2-adrenoceptors was abolished by atenolol (3 microM)
      in a concentration which markedly reduced the effect of isoprenaline on the rate
      of atrial beating. This finding suggests that activation of beta 1-adrenoceptors
      on atrial myocytes by isoprenaline may have resulted in release of one or more
      substance(s) which inhibited stimulation-induced release of noradrenaline,
      presumably by activating prejunctional receptors. The inhibitory effect of
      isoprenaline on noradrenergic transmission was not affected by the prostaglandin
      synthesis inhibitor indomethacin (10 microM) suggesting that prostaglandins were
      not involved.

PMID- 1354163
TI  - Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line:
      comparison with D2 receptor.
AB  - Two cell lines were created by transfecting cDNAs of the human D2 receptor or the
      recently cloned human D3 receptor to CHO cells, and the properties of
      [125I]iodosulpride binding to membranes of these cells were compared. In cell
      lines expressing the D2 receptor subtype where the selectable marker, a
      phleomycin-resistance gene, was cotransfected in a different plasmid, a stable
      expression could be maintained for only few passages. In cell lines expressing
      the D3 receptor subtype, the selectable marker, a dihydrofolate reductase gene,
      was cotransfected in the same plasmid and a stable expression could be obtained.
      In addition, the D3 receptor gene could be amplified in these latter cell lines
      and a high expression level reached (up to 10(6) binding sites per cell). Sodium
      and, to a lesser extent, lithium similarly increased [125I]iodosulpride binding
      to D2 and D3 receptors. In the absence of guanylnucleotide, dopamine had a 24
      fold higher apparent affinity at D3 than at D2 receptors. Gpp(NH)p induced
      rightward shift and steepening of dopamine competition curves at either subtype
      but the effects were more marked at D2 than at D3 receptors. Several agonists and
      antagonists, previously regarded as autoreceptor-selective, displayed higher
      affinities at D3 than at D2 receptors. Although most antagonists used as
      antipsychotics displayed high affinities at the D3 receptor, all were more potent
      at the D2 receptor. However, the ratio of Ki values varied over about 10-fold
      among these compounds, suggesting that they realize differential dopamine
      receptor subtype occupancy during treatments and that this might be reflected in
      their clinical profile.

PMID- 1354164
TI  - Persistent innervation of the rat neocortex by basal forebrain cholinergic
      neurons despite the massive reduction of cortical target neurons. II.
      Neurochemical analysis.
AB  - A significant reduction in the activity of cholinergic enzymes in the neocortex
      is one of the characteristic neurochemical abnormalities in Alzheimer's disease.
      The withdrawal of cholinergic innervation is thought to be due to atrophy and
      degeneration of the cholinergic neurons of the basal forebrain, postulated to
      occur as a consequence of the loss of postsynaptic target neurons and trophic
      factors synthesized by these target cells. To directly test the dependence of
      basal forebrain cholinergic innervation on the presence of target neurons,
      pregnant rats were administered moderate doses of methylazoxymethanol acetate on
      Gestational Days 14 and 15. This results in a 40-70% reduction of cortical
      neurons in offspring of treated dams, but has no significant effect on the
      genesis of basal forebrain cholinergic neurons. In this paper, neurochemical
      analysis of cholinergic enzymes (ChAT and AchE) in 2-month-old offspring reveals
      that the basal forebrain innervates the hypocellular cortex in apparently normal
      fashion, despite the loss of target neurons. The cholinergic innervation of basal
      forebrain target regions was examined at various times through 20 months of age
      and was found to retain the initial high levels of enzymatic activity, without
      any evidence of loss of cholinergic innervation. The preservation of cholinergic
      innervation over 20 months despite the massive loss of target neurons contradicts
      the theory of dependence of basal forebrain cholinergic neurons on target-derived
      trophic support. These results suggest that the degeneration of basal forebrain
      cholinergic neurons in Alzheimer's disease is due to phenomena more complex than
      a reduction in the availability of trophic factors.

PMID- 1354165
TI  - L1 substrate enhances outgrowth of tyrosine hydroxylase-immunoreactive neurites
      in mesencephalic cell culture.
AB  - We have evaluated neurite outgrowth from mesencephalic tyrosine hydroxylase
      positive neurons grown in vitro on different substrates. Cultures of ventral
      mesencephalon from rat embryos (E13) were plated on plastic dishes coated with
      the following substrates: L1, L2/HNK-1 "residual" (mainly J1/160 but also
      tenascin), MAG antigens from mouse brains, laminin, fibronectin, poly-L-lysine,
      RGD peptide, and plastic alone. After 3, 4, and 6 days in vitro, the cultures
      were stained using an antibody against tyrosine hydroxylase (TH), and the length
      of TH-positive neurites was measured by computer-assisted image analysis in a
      double-blind fashion. L1 antigen had a significant positive effect on neurite
      outgrowth compared to the other substrates studied. Laminin and fibronectin were
      also favorable substrates. In cultures treated with cytosine arabinoside to
      prevent mitoses and glial proliferation, the positive effect of L1 was abolished,
      but laminin still had a stimulatory effect. These data indicate that L1 may be
      indirectly involved in differentiation or axonal elongation of substantia nigra
      dopaminergic neurons and suggest a complex effect involving both neurons and glia
      on dopaminergic neurite development.

PMID- 1354166
TI  - Effect of chronic treatment with (+)-PHNO, a D2 agonist in MPTP-treated monkeys.
AB  - A group of four drug naive Macaca fascicularis were rendered parkinsonian with
      the neurotoxin 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine and then treated
      chronically with (+)-PHNO, a potent D2 agonist. After several days, dyskinesia
      appeared in all animals. At this point, the daily dose of (+)-PHNO was replaced
      by a dose of the D1 agonist CY 208-243. The substitution by CY 208-243 reproduced
      the same dyskinesia observed with (+)-PHNO. The administration of the DA
      synthesis inhibitor AMPT (alpha-methyl-p-tyrosine methyl ester) blocked the
      dyskinetic and antiparkinsonian effect of (+)-PHNO, and those effects were
      reestablished by the addition of a subthreshold dose of CY 208-243. Our results
      show that a selective D2 agonist is capable of inducing dyskinesia and suggest
      some kind of cooperation between D1 and D2 receptors in the antiparkinsonian and
      dyskinetic effect produced by (+)-PHNO.

PMID- 1354168
TI  - Recombinant interleukin-2 (rIL-2) in acquired immune deficiency syndrome (AIDS):
      preliminary report in patients with lymphoma associated with HIV infection.
AB  - In an ongoing phase II study, 12 patients with lymphoma and HIV infection were
      treated with zidovudine (ZDV) and recombinant interleukin-2 (rIL-2) to evaluate
      if this association may produce beneficial effect on the immunologic status and
      the outcome of lymphoma. The protocol included daily doses of rIL-2 at 6 MIU/m2
      over 5 days in c.i. per week for a total 4 courses; ZDV was associated at 600
      mg/d in the period under study. An improved CD4 count, exceeding 2- to 4-fold the
      basal count, was obtained in patients with a basal CD4 number greater than
      100/microliters accompanied by a significant increase of NK and LAK activity (p
      less than 0.001). From the clinical point of view the reduction of tumor
      manifestation was proportional to CD4 basal number; 2 patients from those with
      CD4 greater than 100/microliters obtained a complete remission after rIL-2 and
      ZVD. The p24 antigen, taken as parameter of viral replication, remained
      invariably negative after rIL-2 and ZDV in patients already negative and became
      negative in 1 patient previously positive. Our conclusion is that the association
      of rIL-2 and AZT is safe and useful in patients with lymphoma and HIV infection.

PMID- 1354167
TI  - Hypoxia increases extracellular concentrations of excitatory and inhibitory
      neurotransmitters in subsequently induced seizure: in vivo microdialysis study in
      the rabbit.
AB  - It is uncertain whether a brief hypoxic exposure exerts long lasting effects on
      central nervous system amino acid neurotransmission. The purpose of this study
      was to test the hypothesis that a short period of hypoxia would affect release of
      excitatory and inhibitory amino acids during subsequent bicuculline-induced
      seizure. Utilizing in vivo microdialysis in cerebral cortex of rabbits, we
      observed no significant increase in extracellular fluid (ECF) concentrations of
      the excitatory amino acids, glutamate and aspartate, or the inhibitory amino
      acids, GABA and taurine, during a 30-min exposure to hypoxia (FiO2 = 0.08). In
      addition, there was no significant change in these amino acids during
      uncomplicated seizure. However, when seizure was complicated by a preceding
      period of hypoxia, there was a marked and progressive rise in both excitatory and
      inhibitory amino acids in ECF. We conclude that a short period of hypoxia, which
      itself does not cause changes in ECF concentrations of excitatory amino acids,
      may nonetheless contribute to neuronal injury by altering the levels of ECF amino
      acids during a subsequent insult.

PMID- 1354169
TI  - Study designs of adverse events in asthma treatment.

PMID- 1354170
TI  - Beta-agonists--friends or foes?

PMID- 1354171
TI  - Regular beta-agonist therapy--the quality of the evidence.

PMID- 1354172
TI  - Essential catalytic role of Glu134 in endo-beta-1,3-1,4-D-glucan 4
      glucanohydrolase from B. licheniformis as determined by site-directed
      mutagenesis.
AB  - Site-directed mutagenesis experiments designed to identify the active site of
      Bacillus licheniformis endo-beta-1,3-1,4-D-glucan 4-glucanohydrolase (beta
      glucanase) have been performed. Putative catalytic residues were chosen on the
      basis of sequence similarity analysis to viral and eukaryotic lysozymes. Four
      mutant enzymes were expressed and purified from recombinant E. coli and their
      kinetics analysed with barley beta-glucan. Replacement of Glu134 by Gln produced
      a mutant (E134Q) that retains less than 0.3% of the wild-type activity. The other
      mutants, D133N, E160Q and D179N, are active but show different kinetic parameters
      relative to wild-type indicative of their participation in substrate binding and
      transition-state complex stabilization. Glu134 is essential for activity; it is
      comprised in a region of high sequence similarity to the active site of T4
      lysozyme and matches the position of the general acid catalyst. These results
      strongly support a lysozyme-like mechanism for this family of Bacillus beta
      glucan hydrolases with Glu134 being the essential acid catalyst.

PMID- 1354173
TI  - A novel specific binding site for anxiolytic homophthalazines in the rat brain.
AB  - Radioligand binding studies were performed in order to elucidate the mechanism of
      action of anxiolytic-neuroleptic homophthalazines. Rat striatal membrane
      preparations were found to bind 3H-EGIS 6775 [3H-GYKI-52 322, 3H-(1-(4
      aminophenyl)-4-methyl-7,8-dimethoxy-5H-homophthalazine)] in a specific and
      displaceable manner. Several other brain regions tested were devoid of similar
      binding activity. Saturation analysis revealed that binding affinity was in the
      10(-8)-10(-7) M range. Binding was enhanced by Mg2+ ions and, to a smaller extent
      by Ca2+ ions. The binding principle was sensitive to heat or trypsin treatment.
      This specific binding site appears, according to competition studies, different
      from the receptors whose presence in the rat striatum has been reported earlier.

PMID- 1354174
TI  - [Effect of hypoxic hypoxia on the endocrine function of the pancreas in rats].

PMID- 1354175
TI  - [Effect of various neurotropic drugs on chronic hyperreflexia in rats after
      cordotomy].
AB  - Substances modulating calcium permeability of cell membrane (verapamil imidazol,
      4-aminopyridine), decreasing motor activity (meprobamate) and blocking
      adrenoreceptors (clophelin, propranolol, droperidol, aminazine++ have been
      studied for their action on the monosynaptic discharge of the ventral roots (MD
      VR) reinforced due to chronic cutting of the spinal cord. It is found that
      verapamil and meprobamate depress more strongly MD VR of rats with chronic
      cutting of the spinal cord than of those with the acute one. Imidazol and 4
      aminopyridine reinforcing MD VR of rats with acute cutting of the spinal cord
      have no influence on the analogous index of rats with chronic cutting of the
      spinal cord. Adrenoblockers do not change the amplitude of MD VR in both groups
      of the animals.

PMID- 1354176
TI  - Delegation of responsibilities in maternal care in developing countries. Workshop
      on obstetric and maternal care. Singapore, September 8-10, 1991.

PMID- 1354177
TI  - Maternal mortality: community-based interventions.
AB  - Maternal mortality is one of the great neglected problems of health care in
      developing countries. The World Health Organization estimates that approximately
      500,000 women die each year from pregnancy-related causes, over 98% of these
      deaths occurring in the developing world, where maternal mortality is as much as
      100 times higher than rates seen in industrialized countries. The most common
      causes include obstructed labor and ruptured uterus, postpartum hemorrhage,
      eclampsia, postpartum infection and complications of illegal abortion. It is
      suggested that no new or costly technologies are needed; rather that appropriate
      priority setting and allocation of needed resources are essential to the solution
      of the problem. There are few interventions that hold much hope of success at the
      village level, although antibiotics, ergotrate, and sedatives might be
      productively utilized, after appropriate training. Overall, however, networks of
      maternity care facilities, trained personnel, and means of transport are
      necessary to provide needed emergency maternity care services.

PMID- 1354178
TI  - General principles in delegation of maternity functions to community-based health
      workers.
AB  - Following a review of the general principles in delegation of responsibility, the
      functions to be delegated are presented together with minimal criteria for
      training to acquire required skills. Problems arising from delegation are
      reviewed as well as possible solutions which include modification of some
      standard procedures. It is concluded, drawing from case summaries, that effective
      delegation needs strong leadership of maternal health teams buttressed with
      national political, professional, and community support.

PMID- 1354179
TI  - Rural maternity care in Sierra Leone.
AB  - The training and duties of a new category of health worker, the Maternal and
      Child Health Aide, is described. She is a literate women recruited from the place
      where she will eventually work. She has become the immediate supervisor of the
      traditional birth attendants (TBAs), who continue to conduct most deliveries in
      Sierra Leone.

PMID- 1354180
TI  - Delegation of responsibility in maternity care in Karawa rural health zone,
      Zaire.
AB  - Karawa Health Zone (KHZ) located in northwestern Zaire, comprises 19,000 km2 with
      about 340,000 inhabitants. As part of an expanding primary health care program,
      KHZ officials instituted an extensive outreach program to increase access of
      women to maternity care. General practitioner (GP) doctors, nurses, midwives,
      auxiliaries, and traditional birth attendants share responsibilities in
      delivering maternity care services. Nurses and midwives perform most of the
      obstetric functions at the Karawa Hospital Maternity Center. Data from 1988 to
      1990 show that nurses and midwives attended 98% of normal deliveries and 81% of
      the complicated ones. Selected nurses performed cesarean section routinely. There
      was no significant difference in maternal and neonatal outcomes for cesarean
      section performed by nurses and GPs. Physicians on staff provided support through
      monitoring, supervision, training, and care for the most complicated cases.

PMID- 1354181
TI  - Mozambique--delegation of responsibility in the area of maternal care.
AB  - The shortage of physicians in Mozambique has necessitated the training and
      delegation of maternity care to other available health personnel, such as
      traditional birth attendants, midwives, and nurses. In addition, surgical
      technicians have been trained to perform major surgical procedures, including
      cesarean sections and hysterectomies.

PMID- 1354182
TI  - Life-saving skills training for midwives: report on the Ghanaian experience.
AB  - The shortage of rural-based physicians in Ghana has led to a decision to provide
      short term courses to rural midwives on the treatment of those obstetric
      conditions that are the main causes of maternal mortality. A description of this
      ongoing training is provided.

PMID- 1354184
TI  - Appropriate training for maternal health and the attributes of the trainer.
AB  - This review describes the qualities which those who are trainers in safe
      motherhood and other programs should display. The educational principles and
      objectives for maternal health workers, based on the tasks which they have to do
      and expressed in the skills and competences they must attain, are related to
      practical methods of training. Problem-based learning is advocated and the value
      of distance education for rural workers is discussed.

PMID- 1354183
TI  - Delegation of obstetric care in Indonesia.
AB  - An intervention and a control area were selected. Results of the intervention,
      which consisted of training TBAs, midwives, and health center doctors, were
      positive inasmuch as there was an increase in referrals of breech presentation,
      prolonged labor and intrapartum fever in the intervention area. Pregnant women in
      general were also more often referred in the intervention area as compared to the
      control area. The same outcome was seen in referrals of neonates weighing under
      2000 or more than 4000 g. At the district hospital level, a great number of
      procedures were left to general practitioners with quite satisfactory results.
      Conclusions drawn from our experience are that: (1) obstetric care must of
      necessity be delegated to TBAs, midwives, and general practitioners; (2) TBAs can
      be taught to recognize danger signs; (3) general practitioners are able to do
      such procedures as curettage, vacuum or forceps deliveries, and manual removal of
      placenta.

PMID- 1354185
TI  - Traditional birth attendant training: sharing experiences.
AB  - The experiences in TBA training in five countries are contrasted. Successful
      training must impart improved skills to the TBAs and follow-up that both provides
      continuing support and meets the self-interest of the TBAs. The preference of
      mothers for services of TBAs is explained.

PMID- 1354186
TI  - Criteria for the selection of experiences and content in midwifery education.
AB  - Selection of content and learning experiences for any educational endeavor is
      based on the aim and objectives for setting up the program, and the competencies
      required of graduates of the school. To exclude those experiences that will lead
      to skill in the management of obstetric emergencies, and at the same time expect
      midwives to function independently in rural communities is a negation of basic
      curriculum planning principles. The range of experiences available to the
      contemporary curriculum planner in the health field is infinite. However, due to
      the changing nature of societal needs in the health field, and the rapid
      obsolescence of previously held assumptions about health care services and the
      role of midwives, selection of experiences requires creativity and well defined
      criteria for judgment. Those suggested in this paper are validity,
      comprehensiveness, pattern, balance, relevance, and continuity. The six criteria
      are discussed to show the relevance of each to some of the current weaknesses in
      midwifery education in Nigeria.

PMID- 1354187
TI  - Alternative model for low risk obstetric care in Third World rural and peri-urban
      areas.
AB  - The Program for Integrated Health Care (PROAIS) has devised ways and means of
      reaching the traditional birth attendant, here called empiric midwife and
      training her to offer adequate, hygienic care at delivery for her low-risk
      patients. She is taught to recognize the high-risk patient and to send her to the
      weekly prenatal clinics staffed by physicians and registered nurses. The empiric
      midwife can also be taught prenatal care, detection of cervical and breast
      cancer, family planning, and the importance of breastfeeding. These women are
      considered colleagues by their formal medical counterparts and are treated as
      such. More recently some of the more capable have been placed on County Health
      Department payrolls.

PMID- 1354188
TI  - Evaluation of maternal health programs: approaches, methods and indicators.
AB  - Evaluation of maternal health services is an essential function of any health
      system. Single or multiple aspects of a program can be evaluated but they must be
      clearly defined. To assess success of a program the dimensions of coverage,
      equity, quality, women's satisfaction, efficiency and cost-effectiveness must be
      considered. These can be measured according to some standard criteria, and
      various methods are described, including randomized clinical trials, randomized
      community trials, before and after studies, and observational studies, including
      the case-control approach and confidential inquiries into maternal deaths.
      Indicators to assess effectiveness of a maternal health program may relate to
      structure, i.e., available resources or organizational arrangement; process,
      including changes in quantity of services provided; or outcome indicators that
      measure maternal mortality or morbidity.

PMID- 1354189
TI  - Midwives: key rural health workers in maternity care.
AB  - The most acceptable and attainable rural health worker for maternity care is
      frequently the traditional birth attendant or other personnel lacking clinical
      skills to treat life-threatening emergencies. When first referral level
      facilities are also poorly staffed and ill-equipped to deal with these
      emergencies, this again points to the need for training of and delegation to the
      trained midwife in rural areas. Unfortunately, their number is declining in rural
      areas of some countries most in need, e.g., Tanzania. Elsewhere, midwifery skills
      and knowledge have been integrated into basic nursing education, but practical
      skills are only developed postbasically when midwife educators are expert
      clinicians. The graduates of such training could be delegated responsibility for
      many lifesaving procedures in obstetric care. Successful clinical experience in
      use of these responsibilities will earn the midwife's needed community reputation
      as a trusted health worker.

PMID- 1354190
TI  - Somatostatin is an essential paracrine link in acid inhibition of gastrin
      secretion.
AB  - We studied the functional coupling between antral somatostatin and gastrin cells
      in pigs using isolated perfused preparations of the antrum with intact supply of
      the vagus nerves. Luminal acidification significantly inhibited gastrin secretion
      to 61 +/- 3% of basal secretion and increased somatostatin output 9-fold. Intra
      arterial infusion of somatostatin to concentrations of 10(-10) and 10(-9) mol/l
      inhibited gastrin secretion to 18 +/- 9 and 33 +/- 11% of basal secretion.
      Electrical stimulation of the vagus nerves and intra-arterial infusion of gastrin
      releasing polypeptide (GRP; 10(-9) mol/l) significantly increased both gastrin
      and somatostatin secretion. Addition to the perfusate of Fab fragments of
      somatostatin antibodies abolished the effect of somatostatin at 10(-10) mol/l and
      the acid inhibition of gastrin secretion, but had no effect on the response to
      vagus stimulation of GRP infusion. We conclude that a local release of
      somatostatin is essential for the acid-induced inhibition of gastrin secretion,
      whereas changes in the local somatostatin concentration are unlikely to play a
      major role in vagally or GRP-induced gastrin secretion.

PMID- 1354191
TI  - Expression of a zebrafish caudal homeobox gene correlates with the establishment
      of posterior cell lineages at gastrulation.
AB  - This paper deals with the first identification of a caudal cDNA containing a
      homeobox of the Drosophila caudal family in the zebrafish. A cDNA library from
      late gastrula stage embryos was constructed and screened with a mouse Cdx 1
      homeobox probe. A 1.6 kb cDNA clone containing a homeobox related to other caudal
      homeoboxes was isolated and called cdx[Zf-cad1]. Analysis of the predicted 301
      amino acid translation product reveals additional regions of homology outside the
      homeodomain with other members of the caudal family. Particularly, the cdx[Zf
      cad1] putative protein shares a conserved N-terminal region with its chicken
      homolog CHox-cad. Transcripts are first detected just before the onset of
      gastrulation. At the beginning of gastrulation, a single 1.8 kb cdx[Zf-cad1]
      transcript is located near the blastoderm margin with a high level of expression
      restricted to the epiblast. At this stage, the hypoblast is clearly negative. At
      the end of gastrulation, cdx[Zf-cad1] is widely expressed in vegetal (i.e.
      prospective posterior) epiblast and hypoblast, with a somewhat weaker expression
      in the dorsal hypoblast. During somitogenesis, cdx[Zf-cad1] exhibits a posterior
      regionalization in the neurectoderm. In contrast, no expression is detected in
      the mesoderm of 22 h embryos (late somitogenesis). Posterior endoderm is also
      positive at this stage. cdx[Zf-cad1] transcripts cease to be detected about 48 h
      after fertilization. They are undetectable in the adult, particularly in female
      gonads. The pattern of cdx[Zf-cad1] expression during and after gastrulation is
      consistent with its possible involvement in the regionalization of the embryo at
      these stages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354192
TI  - [Conference: "Individual human psychophysiologic features and professional
      activity" (November 13-15. 1991, Cherkassy)].

PMID- 1354193
TI  - HLA class II molecules and autoimmune hepatitis susceptibility in Japanese
      patients.
AB  - To investigate the association between autoimmune hepatitis and HLA alleles in
      Japanese patients, serological typing and class II genotyping were performed
      using the polymerase chain reaction-restriction fragment length polymorphisms
      (PCR-RFLP) method. Serological typing showed that HLA-B54, -DR4, -DR53, and -DQ4
      were significantly more frequent in patients with autoimmune hepatitis than in
      controls. HLA-DR4 was most frequently associated with autoimmune hepatitis
      (88.7%). In PCR-RFLP typing, the frequency of DRB1*0405 was significantly higher
      in autoimmune hepatitis than in controls. However, there was no significant
      difference in the frequency of Dw between the patients and the controls who were
      DR4-positive. The significant increase observed in DQA1*0301 and DQB1*0401 was
      explained by a linkage disequilibrium with DR4. Six DR4-negative patients had
      DR2, but there was no significant difference in the frequency of the DR2
      associated Dw-alleles compared with the DR2-positive controls. No DPB1 allele was
      significantly associated with autoimmune hepatitis. These findings suggest that
      the basic amino acid at position 13, which is present only on the DR2 and DR4 B1
      molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to
      autoimmune hepatitis among the Japanese.

PMID- 1354194
TI  - Dental nonsteroidal anti-inflammatory drugs and prostaglandin-based drug
      interactions, Part two.

PMID- 1354196
TI  - Characterization of Serpulina (Treponema) hyodysenteriae and related intestinal
      spirochetes by ribosomal RNA gene restriction patterns.
AB  - Serpulina (Treponema) hyodysenteriae strain A-1 partially purified rRNA, labelled
      with photobiotin, was used as a non-radioactive probe to identify the rRNA gene
      restriction patterns of S. hyodysenteriae strains and other spirochetes. Sau3A
      restriction enzyme digests resulted in similar rRNA gene restriction patterns in
      S. hyodysenteriae strains from five different countries. Some S. hyodysenteriae
      strains could be differentiated by variations in their rRNA gene restriction
      patterns after cleavage of DNA by restriction enzymes SspI or BglII. S. innocens
      and Treponema succinifaciens, non-pathogenic pig intestinal spirochetes, had rRNA
      gene restriction patterns that differed markedly from the S. hyodysenteriae
      patterns, and from each other.

PMID- 1354195
TI  - Rapid identification of bacteria of the Comamonadaceae with amplified ribosomal
      DNA-restriction analysis (ARDRA).
AB  - Ribosomal rRNA gene fragments (rDNA) encompassing the 16S rDNA, the 16S-23S rDNA
      spacer region and part of the 23S rDNA of 95 strains belonging to 13 well
      described taxa of the eubacterial family Comamonadaceae (beta subclass of the
      Proteobacteria or rRNA superfamily III) were enzymatically amplified using
      conserved primers. The fragments of approximately 2400 base pairs were subjected
      to restriction analysis. Restriction fragment length patterns obtained with HinfI
      enabled us to distinguish 9 of the 13 taxa studied. Restriction with CfoI was
      necessary to differentiate Acidovorax delafieldii from A. temperans and
      Hydrogenophaga flava from H. pseudoflava. The results indicate that amplified
      rDNA restriction analysis is a simple and reliable tool for the identification of
      bacterial species.

PMID- 1354197
TI  - [Elevated serum levels of ICAM-1 in Wegener's granulomatosis].
AB  - Circulating soluble ICAM-1 (sICAM-1) isoforms are known to be elevated in
      inflammatory and autoimmune disorders (SLE, RA). A correlation between levels of
      circulating sICAM-1 and disease activity was described (5). In sera from 31
      patients suffering from histologically confirmed Wegener's granulomatosis (WG)
      elevated levels of ICAM-1 were now detected in this primary systemic vasculitis.
      In generalized active disease circulating ICAM-1 levels were significantly higher
      when compared to remission and healthy control individuals. Sera from WG patients
      collected during intercurrent infections while on immunosuppressive drugs showed
      no elevation of circulating ICAM-1.

PMID- 1354198
TI  - [Enhanced lymphocyte proliferation in the presence of epidermal cells of HIV
      infected patients in vitro].
AB  - Clinical observations show that the HIV infection is often associated with
      affections of the skin. In order to examine the involvement of the epidermal
      immune system in the HIV infection, we determined accessory cell function of
      epidermal cells from HIV-1-infected patients. For this we measured the
      proliferative response of enriched CD(4+)-T-lymphocytes from HIV-infected
      patients and noninfected controls to stimulation with anti-CD3 and IL-2 in the
      presence of epidermal cells; the enhancement of the response is dependent on the
      presence of functionally intact accessory cells. The capacity of epidermal cells
      to increase the anti-CD3-stimulated T-cell proliferative response was
      significantly enhanced in HIV patients (CDC III/IVA) as compared with noninfected
      donors. It is discussed, whether the increased activity of epidermal cells from
      HIV-infected patients may be responsible for several of the dermal lesions in the
      course of an HIV infection as due to an enhanced production and release of
      epidermal cell-derived cytokines.

PMID- 1354199
TI  - Presence of functional receptors for the Escherichia coli heat-stable enterotoxin
      in the gastrointestinal tract of the chicken.
AB  - Receptors for the Escherichia coli heat-stable enterotoxin (STa) were shown to be
      present throughout the digestive tract of the chicken, with binding activity
      present not only in the intestinal epithelium but also in the intestinal smooth
      muscle. Brush border membrane vesicles (BBMV) purified from chicken enterocyte
      homogenates and plasma membranes (SMPM) purified from intestinal smooth muscle
      homogenates were compared with pig enterocyte BBMV. All had similar 125I-STa
      binding affinities, but the 50% effective concentration for STa activation of
      guanylate cyclase was higher in SMPM than in BBMV. Maximal STa-stimulated
      guanylate cyclase activities were similar in chicken and pig BBMV and were seven-
      to eightfold higher than in SMPM, and the STa receptor density was five- to
      sixfold higher. Patterns unique to each membrane were demonstrated after affinity
      labelling of STa receptors with 125I-STa, sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis, and autoradiography. The results demonstrated STa-stimulated
      guanylate cyclase activity in birds as well as mammals and suggested that there
      are different functional STa receptors in chicken BBMV and SMPM.

PMID- 1354201
TI  - Immune CD4+ T cells specific for Theileria parva-infected lymphocytes recognize a
      24-kilodalton protein.
AB  - Theileria parva is a protozoan parasite that infects and transforms bovine
      lymphocytes. Here we report the partial purification of a T. parva-specific
      protein from infected lymphocytes that is recognized by CD4+ parasite-specific T
      cell clones derived from immune cattle. T. parva-infected lymphocytes were
      homogenized in Dulbecco's phosphate-buffered saline in the presence of protease
      inhibitors. The antigen was purified from a postmicrosomal supernatant by using a
      combination of DEAE-cellulose chromatography and hydroxylapatite column
      chromatography. After labelling with 125I, the antigen preparation was subjected
      to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and found to contain
      8 to 10 proteins. This preparation was subjected to chromatography in phosphate
      buffered saline on HPLC TSK-250/125 columns coupled in tandem. A radiolabelled
      protein of M(r) 24,000 correlated with antigenic activity.

PMID- 1354200
TI  - Genetic relationship of putative colonization factor O166 to colonization factor
      antigen I and coli surface antigen 4 of enterotoxigenic Escherichia coli.
AB  - Plasmid DNA from two strains of enterotoxigenic Escherichia coli harboring genes
      encoding coli surface antigen 4 (CS4) and from seven Indian enterotoxigenic E.
      coli isolates cross-hybridized at low stringency but not at high stringency with
      two polynucleotide probes derived from the colonization factor antigen I (CFA/I)
      operon. Low-stringency Southern blot hybridization of PstI-digested plasmid DNA
      from the seven Indian isolates yielded characteristic restriction fragment
      patterns, distinct from those of CS4- and CFA/I-associated plasmid DNA. Two of
      the Indian strains were transformed with a recombinant plasmid harboring the cfaD
      gene, which encodes a positive regulator of CFA/I and CS4 genes. The cfaD
      transformants produced large amounts of putative colonization factor O166
      (PCFO166) irrespective of whether the nutrient agar contained bile salts, a
      growth factor otherwise required for adequate PCFO166 expression. A considerable
      interstrain variation in the level of PCFO166 production could be explained by
      differences in the proportion of bacteria that were fimbriated, as visualized by
      electron microscopy. The N-terminal amino acid sequence of PCFO166 fimbrial
      protein showed a high degree of homology with the corresponding sequences of
      CFA/I and CS4.

PMID- 1354202
TI  - P-glycoprotein transports corticosterone and is photoaffinity-labeled by the
      steroid.
AB  - Multi-drug-resistant cells overproduce a 130-180-kDa integral membrane
      phosphoglycoprotein known as P-glycoprotein which acts as an energy-dependent
      drug efflux pump. While P-glycoprotein has been shown to transport hydrophobic
      anti-tumor drugs out of multi-drug-resistant cells in tissue culture, its
      endogenous substrates remain unknown. This report shows that 3H-corticosterone
      can specifically photoaffinity label P-glycoprotein. Furthermore, corticosterone
      is effluxed from multi-drug-resistant cells by P-glycoprotein. These data suggest
      that corticosterone may be an endogenous substrate for P-glycoprotein.

PMID- 1354203
TI  - Differentiation-related expression of adhesion molecules and receptors on human
      neuroblastoma tissues, cell lines and variants.
AB  - The expression of cellular adhesion molecules (CAM) involved in cell adhesion and
      immune recognition was measured on neuroblastoma tissue samples, on a
      neuroblastoma (NB) cell line, SK-N-SH, and on 3 phenotypically different
      variants, SH-SY5Y, SH-EP, SH-IN, representing neuronal, Schwannian/glial or
      intermediate NB-cell types. Immunohistochemical analysis of CAM expression by NB
      and related tumors at different stages of differentiation revealed a co
      expression of several CAM (ICAM-1/CD54, LFA-3, VLA-2 and HLA-ABC) associated with
      low stages and more highly differentiated NB tumors and peripheral
      neuroepitheliomas (PN). In contrast, N-CAM was uniformly expressed on all NB
      tumors. Flow cytometric analysis of CAM surface expression by SK-N-SH and variant
      cells revealed highly variable phenotypes. Expression of ICAM-1, LFA-3, VLA-2 and
      HLA-ABC molecules was associated with the epithelial cell type represented by the
      SH-EP variant. In contrast, low expression of these molecules and high expression
      of N-CAM was associated with the neuronal SH-SY5Y cells. Exposure of the NB cells
      to differentiation inducers (retinoic acid, 5'-bromodeoxyuridine and phorbol
      esters) and cytokines (tau-interferon, alpha-tumor necrosis factor) resulted in a
      variable up-regulation of the expression of all CAMs, except N-CAM, regardless of
      the type of differentiation induced. In an attempt to establish a link between
      the pattern of expression of CAM on NB cells and their susceptibility to natural
      killer (NK) or lymphokine-activated killer (LAK) cell lysis, the analysis
      revealed that NB cells expressing CAM and a differentiated phenotype were less
      susceptible to NK lysis, but no difference in the sensitivity of the NB cell
      types to LAK effectors was observed. Treatment of NB target cells with cytokines
      or PMA decreased their susceptibility to NK and LAK lysis, while induction of
      differentiation with RA or BUdR resulted in no changes in the sensitivity to NK
      and LAK lysis. In conclusion, expression of HLA-ABC and several co-regulated CAMs
      was shown to be associated with a differentiated phenotype in NB, with an overall
      decreased sensitivity to NK/LAK effector cells.

PMID- 1354204
TI  - 'Abraham ... laughed'.

PMID- 1354205
TI  - Reproductive outcome following two ectopic gestations: results after conservative
      surgery.
AB  - In an 11-year period, 106 women were treated for two ectopic pregnancies (EP).
      Thirty-one had been surgically sterilized by the second operation. Of the 75
      women with at least one patent tube, 70 (93%) were followed up regarding
      pregnancy outcome, with a mean follow-up period of 4.5 years. Fifty women had had
      a desire for pregnancy after treatment for the second EP. Of these, 26 (52%) did
      not achieve any conception; 16 (32%) experienced at least one more EP, and 13
      (26%) had at least one intrauterine pregnancy. There were a total of 46
      pregnancies, of which 21 (46%) were ectopic and 16 (35%) were carried on term.
      When conservative surgical techniques had been performed at the first EP, the
      number of intrauterine pregnancies achieved after the second EP was doubled, and
      the risk for a third EP was not raised. There was found no statistical difference
      in laterality of the second EP when the first operation was conservative. It is
      concluded that women experiencing repeat EP have severely impaired future
      fertility, with a high risk of a third EP if they conceive.

PMID- 1354206
TI  - Human urinary glycosaminoglycans as accurate method for ovulation detection.
AB  - Urinary glycosaminoglycans (GAGs) content showed a characteristic pattern of
      fluctuation during normal and hormonally induced cycles with a distinct peak at
      ovulation. This peak of maximal GAGs concentration (106.7 +/- 46.2 micrograms/mL
      in urine) was centered according to the day of the midcycle LH surge, which
      serves as the reference point, designated day 0. All cycles are presumed to be
      ovulatory on the basis of biphasic BBT nadir, ultrasonographic studies, and
      progesterone assays (greater than 5 ng/mL of serum) during the secretory phase.
      In hormonally induced menstrual cycles, a noticeable increase in GAGs
      concentration (70%) was observed. This indirect evidence suggests a possible
      correlation between GAGs content and hormonal effect. All types of GAGs, with the
      exception of heparin, have been found in urine, chondroitin sulfate C being the
      major component at time of ovulation. These results strongly suggest that urinary
      GAGs determination is a precise method for ovulation detection.

PMID- 1354207
TI  - Cervical cerclage in uterine malformations.
AB  - This retrospective study represents our experience with cervical cerclage
      (suture) in pregnancies with uterine malformation. Seventeen patients with
      uterine malformations were involved. In these patients, the outcome of 31
      gestations with cervical cerclage was evaluated. Uterine malformation was
      associated with cervical incompetence in 41% of the patients. Term delivery rate
      and fetal loss were observed in 56% and 26% of pregnancies, respectively. Infant
      salvage was not significantly different regardless of whether cervical
      incompetence was present or absent. A prolonged hospital stay and frequent use of
      tocolysis were noted during gestations with cerclage. Our data suggest that the
      outcome of pregnancies with uterine malformation was not improved by cervical
      cerclage when the indication for cerclage was the malformation itself.

PMID- 1354208
TI  - Comparison of intrauterine insemination, intracervical insemination, and timed
      intercourse in women treated with human menopausal gonadotropin.
AB  - The effects of intrauterine insemination (IUI), intracervical insemination (ICI),
      and timed intercourse (TI) in women who were treated with human menopausal
      gonadotropin (hMG) for anovulation were evaluated. The pregnancy rates per cycle
      following IUI (70 cycles), ICI (62 cycles) and TI (158 cycles) were 20%, 9.6%,
      and 17.7%, respectively; these differences are not statistically significant. The
      abortion rate and the multiple pregnancy rate were also not significantly
      different. This report suggests that in women who are undergoing treatment with
      hMG, there is no added benefit from artificial insemination (either intrauterine
      or intracervical insemination) over timed intercourse.

PMID- 1354209
TI  - On the relationship between endocrine and ovulatory abnormalities, and polycystic
      ovaries as diagnosed by ultrasonography.
AB  - The present study was undertaken to investigate the relationship between serum
      testosterone levels, the menstrual cycle, and polycystic ovaries as shown by
      ultrasonographic methods. The patients were divided into four groups: (1) cases
      with normal-appearing ovaries and with regular menstruation (control); (2) cases
      with normal ovaries on ultrasound, but with abnormalities of the menstrual cycle
      (MA); (3) cases with polycystic ovaries, but normal menstrual cycle (PCO); (4)
      cases with both polycystic ovaries and menstrual abnormalities (PCOMA). The
      results were as follows. (1) The ovarian area was significantly larger in the
      PCOMA group than in the control group. (2) The number of cases with elevated LH
      (greater than 30 mIU/mL) was significantly higher in the PCOMA group than in the
      other groups. (3) In comparison with controls, the percentage of cases with
      LH/FSH ratios greater than 3.0 was significantly higher in all three groups. (4)
      The estrone/17 beta-estradiol ratio for the PCOMA group was significantly greater
      than those of the other groups. (5) The testosterone levels of the PCO and PCOMA
      group were significantly greater than the control value. (6) The percentage of
      endocrine criteria (LH greater than 30 mIU/mL or LH/FSH ratio greater than 3.0,
      estrone/17 beta estradiol ratio greater than 1.0 testosterone greater than 75,
      greater than 100, and greater than 125 ng/dL) for PCOMA was significantly higher
      than that of the MA group and the control group, but not significantly greater
      than the PCO group. It is suggested that morphological changes in the ovaries
      show a closer correlation with abnormalities of endocrine function than does the
      presence or absence of abnormalities of the menstrual cycle.

PMID- 1354210
TI  - CA 125 levels in monitoring therapy for endometriosis and in prediction of
      recurrence.
AB  - CA 125 levels were measured in the serum of 18 patients with laparoscopically
      diagnosed stage 2 to stage 4 endometriosis (American Fertility Society
      classification) and in eight normally cycling control women. All endometriosis
      patients were treated medically with either Danazol or Buserelin. CA 125 levels
      were measured during treatment and during the 18-month follow-up period. The mean
      CA 125 level in women with endometriosis was significantly higher than that
      observed in normal women (28.6 +/- 5.1 (+/- SE) units/mL vs. 11.1 +/- 1.1
      units/mL). However, there was considerable overlap of values between controls and
      patients with stage 2 disease. The levels in patients with stage 3 or stage 4
      disease were always greater than 20 units/mL. There was a significant positive
      correlation (r = .51) between the implant score and CA 125 levels, while there
      was no correlation between the total score (which includes adhesions and
      implants) and the CA 125 levels. Four of the patients who had recurrence of
      symptoms approximately 1 year after treatment had CA 125 levels close to
      pretreatment levels, and recurrence of endometriosis was confirmed by
      laparoscopy. The CA 125 levels in the rest of the patients remained suppressed
      during the follow-up periods. These results indicate that (1) CA 125 level can
      predict active endometriosis lesions in patients with stage 3 and stage 4
      endometriosis, but is of no value for predicting adhesions; (2) CA 125 levels are
      useful in monitoring therapy during treatment; (3) during the follow-up period,
      elevations in CA 125 might predict recurrence of disease in women with stage 3
      and stage 4 endometriosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354211
TI  - Morphological and quantitative study of multinucleated bodies appearing in rat
      seminiferous tubules after bilateral caput epididymectomy.
AB  - Adult Wistar rats were bilaterally caput epididymectomized and the effects on
      testicular germinal epithelium and formation of multinucleated bodies were
      studied and quantified at 2, 4, 7, 14, 21, and 28 days after surgery. Sham
      operated and bilaterally efferentectomized animals served as controls. No
      alterations were found in sham-operated animals. Efferentectomized animals showed
      a progressive alteration of the seminiferous tubule epithelium and a (very
      occasional) presence of multinucleated bodies. Epididymectomized animals
      presented a progressive degeneration of the germinal epithelium, which was almost
      complete at 28 days. This epithelial degeneration was accompanied by the
      formation of multinucleated bodies from germinal cells, whose number and
      characteristics varied with the experimental interval. The multinucleated bodies
      described here resemble the multinucleated cells mentioned by other authors. They
      do not seem to be cellular; instead, they appear to be debris, since electron
      microscopic observations do not reveal a plasma membrane.

PMID- 1354212
TI  - Characteristics of natural conceptual cycles occurring in a prospective study of
      sex preselection: fertility awareness symptoms, hormone levels, sperm survival,
      and pregnancy outcome.
AB  - A prospective study of sex preselection provided the opportunity to characterize
      the fertile menstrual cycle. We describe from 91 natural conceptual cycles, or
      sub-groups thereof, cervical mucus symptoms, basal body temperature (BBT)
      changes, hormonal characteristics, and the outcome of pregnancy. The cervical
      mucus symptoms defined a potential fertile period of 10 days' average length,
      with the "peak" mucus symptom occurring at a mean of day 15.5 of the cycle. A
      fertile period of 9 to 10 days was also indicated by pregnancies resulting from
      single acts of intercourse between -6 and +3 days from ovulation. The BBT chart
      was biphasic in 73 of 76 cycles. The duration of the LH surge as observed in
      early morning urine samples averaged five days, with the peak occurring 1.4 days
      after the onset. Considerable inter-subject variability was seen in the LH
      excretion levels. Hormone measurements of peripheral plasma during the luteal
      phase showed the first detectable presence of hCG between day 7 and day 13 after
      conception. Progesterone concentrations in the midluteal phase exceeded 20 nmol/L
      and tended to be higher than in a comparison group of nonfertile cycles, whereas
      the estradiol concentrations were similar in fertile and nonfertile cycles. The
      birth sex ratio favored males when intercourse preceded ovulation/fertilization
      by two days or longer. While this association was statistically significant, the
      number of pregnancies involved is too small to conclude that the relationship is
      real.

PMID- 1354214
TI  - American Veterinary Medical Association (AVMA) food safety workshop. Arlington,
      Virginia, March 11-13, 1992.

PMID- 1354215
TI  - A producer's perspective of food safety issues.

PMID- 1354213
TI  - Excess of taurine supplementation in rat: effects on GABA-related amino acids in
      developing nervous tissues.
AB  - The effects of taurine supplementation on GABA-related amino acid homeostasis in
      developing nervous tissues of suckling rats were studied. In the first two weeks
      of postnatal growth, cerebral cortex and cerebellum appear more accessible to
      taurine supplementation in comparison to retina; in addition, different changes
      in excitatory/inhibitory amino acids were observed. After the 5th day of life, in
      the retina and cerebellum of taurine-supplemented pups a decrease in GABA levels
      was found; in contrast, in cerebral cortex GABA content significantly increased
      throughout 20 days of postnatal growth. In all nervous tissues studied (except
      for cerebellum) glutamine concentration increased at the 5th day; then in
      cerebellum and in retina, but not in cerebral cortex, a significant decrease
      until the 20th day occurred. Furthermore, in cerebellum and retina taurine
      supplementation decreased glutamate levels, in comparison to controls, at the
      10th and until the 20th day of postnatal life, respectively, whereas in cerebral
      cortex an increase in glutamate level was observed only at the 5th day. In
      conclusion, taurine supplementation, in excess to the usual amount from the
      mother's milk, affected the glutamate compartments in various cell types. The
      changes in GABA-related amino acid concentrations in cerebral cortex, cerebellum,
      and retina may depend on the different pattern of the metabolic processes at
      different maturative stages.

PMID- 1354216
TI  - HLA gene analysis in a Japanese family with hypertrophic cardiomyopathy by
      restriction fragment length polymorphism.
AB  - A large Japanese family with hypertrophic cardiomyopathy (HCM) was examined (n =
      61). Ten of 14 affected family members who showed HCM on the basis of
      electrocardiography and two-dimensional echocardiography were subjected to human
      leukocyte antigen (HL-A)-A,B,C typing by the lymphocyte cytotoxicity test and D,
      DR typing by restriction fragment length polymorphism (RFLP). As control, the HLA
      genotype of 14 non-affected family members was analyzed. HLA typing of the
      affected subjects with HCM revealed a very close association (67%) of HLA-DR
      (4w8) among A,B,C,D and DR. However, the LOD scores of HLA-DR4 and -DR w8 were
      0.693 (theta = 0.35) and 0.642 (theta = 0.30) respectively. These data suggest
      that HLA-loci, analyzed on the basis of RFLP, may not be related with familial
      HCM with or without obstruction.

PMID- 1354217
TI  - Purification and characterization of dipeptidyl peptidase IV in rat liver
      lysosomal membranes.
AB  - Dipeptidyl peptidase IV (m-DPP IV) in rat liver lysosomal membranes was purified
      about 50-fold over the lysosomal membranes with 38% recovery to apparent
      homogeneity, as determined from the pattern on polyacrylamide gel electrophoresis
      in the presence and in the absence of SDS. The enzyme amounts to about 3% of
      lysosomal membrane protein constituents. The purification procedures included:
      extraction of lysosomal membranes by Triton X-100, WGA-Sepharose affinity
      chromatography, hydroxylapatite chromatography, ion exchange chromatography, and
      preparative polyacrylamide gel electrophoresis. The enzyme (M(r) 240,000) is
      composed of two identical subunits with an apparent molecular weight of 110,000.
      The enzyme contains about 12.4% carbohydrate and the carbohydrate moiety was
      composed of mannose, galactose, fucose, N-acetylglucosamine, and neuraminic acid
      in a molar ratio of 14:17:2:24:11. Susceptibility to neuraminidase and
      immunoreactivity of the enzyme in intact tritosomes were examined to study the
      topology of the enzyme in tritosomal membranes. Neuraminidase susceptibility and
      immunoreactivity of the enzyme were not observed in the intact tritosomes until
      the tritosomes had been disrupted by osmotic shock. This result indicated that
      both the oligosaccharide chains and the main protein portion of the enzyme are on
      the inside surface of the tritosomal membranes. Subcellular localization of DPP
      IV was determined by means of enzyme immunoassay, which indicated that bile
      canalicular membranes and lysosomal membranes are the major sites of
      localization, and DPP IV activity in lysosomes was separated into a membrane
      bound form (60%) and a soluble form (40%). Immunoelectron microscopy clearly
      confirmed that DPP IV occurs not only in the bile canalicular domain but also in
      the lysosomes of rat liver.

PMID- 1354218
TI  - Characterization of the bacterially expressed Drosophila engrailed homeodomain.
AB  - To investigate the mechanism of DNA recognition by the homeodomain, truncated
      proteins containing the entire homeodomain encoded by the Drosophila engrailed
      gene were expressed in Escherichia coli. Each protein was accumulated to an
      amount representing more than 40% of the total bacterial protein and recovered in
      the soluble fraction. Of the three truncated proteins, the shortest one (71 amino
      acid residues) was further purified by conventional chromatography. The purified
      engrailed homeodomain (En-HD) protected a DNA sequence, TTAATT, the core element
      of consensus sequences recognized by many other homeodomain proteins, from DNase
      I digestion. UV-CD spectra of the En-HD showed that it mainly consisted of alpha
      helix. Based on one-dimensional 1H-NMR spectra, the tertiary structure of the En
      HD was shown to be stable against temperature up to 50 degrees C and low pH. The
      low pH resistance of the protein was also demonstrated by UV-CD measurement.
      Thus, the current over-production system provides an active and stable
      homeodomain, which is suitable for structure-function analysis.

PMID- 1354219
TI  - Nuclear distribution of PCNA during embryonic development in Xenopus laevis: a
      reinvestigation of early cell cycles.
AB  - The immunocytological distribution of the proliferating cell nuclear antigen
      (PCNA), a protein involved in DNA replication, has been examined during the early
      development of Xenopus laevis. The protein is uniformly detected in nuclei during
      early stages up to the neurula stage. PCNA is detected by its distinctive
      cyclical pattern during early development, remaining detectable only during the
      period of S phase of each cell cycle. Immunological detection of PCNA is
      therefore a useful and specific non-isotopic marker of S-phase cells in the
      embryo. PCNA associates with typical karyomeric structures, suggesting that DNA
      replication starts before the nuclear compartment is entirely formed. At the
      midblastula transition, a new pattern of PCNA staining becomes apparent. First, a
      new type of PCNA staining is detected at the nuclear periphery. Second, mitotic
      clusters with different PCNA distributions suggest that the onset of
      desynchronization of the cell cycle at this stage is not random.

PMID- 1354220
TI  - Ability to organize microtubules in taxol-treated mitotic PtK2 cells goes with
      the SPN antigen and not with the centrosome.
AB  - The SPN antigen plays an essential role in mitosis, since microinjection of
      antibodies causes mitotic arrest. Here we show, by examination of the relative
      locations of SPN antigen, the centrosomal 5051 antigen and tubulin in normal
      mitotic, and in taxol-treated mitotic cells, that the SPN antigen is involved in
      organizing the microtubules of the spindle. The 210 kDa protein defined as SPN
      antigen relocates from the nuclear matrix to the centrosome at prophase, remains
      associated with the poles at metaphase and anaphase, and dissociates from the
      centrosomes in telophase. In taxol-treated mitotic cells, SPN staining shows a
      striking redistribution while 5051 antigen remains associated with centrosomes.
      SPN antigen is seen at the plasma membrane end of the rearranged microtubules.
      SPN antigen is always at the center of the multiple microtubule asters (5 to 20
      per cell) induced by taxol, whereas 5051 again remains associated with the
      centrosomal complex (1 to 2 foci per cell). Microtubule nucleation is associated
      with the SPN antigen rather than with the 5051 antigen. Microinjection of SPN-3
      antibody into taxol-treated mitotic PtK2 cells causes disruption of the asters as
      judged by tubulin staining of the same cells. Finally, SPN antigen extracted in
      soluble form from synchronized mitotic HeLa cells binds to, and sediments with,
      pig brain microtubules stabilized by taxol. This association of SPN antigen with
      microtubules is partially dissociated by 0.5 M NaCl but not by 5 mM ATP. Thus SPN
      antigen binds to microtubules in vitro and seems to act as a microtubular minus
      end organizer in mitotic cells in vivo.

PMID- 1354221
TI  - Comparison of serologic typing, sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis protein analysis, and genetic restriction fragment length
      polymorphism analysis for identification of rickettsiae: characterization of two
      new rickettsial strains.
AB  - In 1990, 17 adult Rhipicephalus turanicus ticks were collected in the south of
      France. Two spotted fever group rickettsiae, Mtu1 and Mtu5, were isolated from
      the hemolymphs of two of these ticks by the centrifugation shell-vial technique
      by using HEL cells. These isolates were compared with reference spotted fever
      group rickettsial serotypes by using three identification methods:
      microimmunofluorescence serologic typing, sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE), and polymerase chain reaction followed by
      restriction endonuclease fragment length polymorphism analysis. The results
      obtained by all these techniques showed that Mtu1 and Mtu5 are each previously
      undescribed rickettsial serotypes. A comparison of the three methods used to
      identify the isolates led us to the conclusion that, in large-scale
      epidemiological studies, the simplest way to identify isolates in ticks is to
      first use the polymerase chain reaction-restriction fragment length polymorphism
      analysis directly on triturated ticks as a screening method to detect interesting
      rickettsiae, and then attempt to isolate rickettsiae from ticks for
      identification by microimmunofluorescence and SDS-PAGE, both of which are time
      consuming and expensive to carry out.

PMID- 1354222
TI  - Ribotyping provides efficient differentiation of nosocomial Serratia marcescens
      isolates in a pediatric hospital.
AB  - Ribotyping with a nonradioactive probing system was used for the epidemiological
      evaluation of 15 Serratia marcescens nosocomial strains isolated from the stools
      of 12 children with no apparent illness in five different hospital wards over a
      20-day period. Our results indicate that the occurrence of S. marcescens
      colonization was the result of the spread of a single epidemiological strain in
      the hematology ward, the oncology ward, and the gastroenterology ward and in two
      neonates in the neonatology ward, suggesting cross-contamination between the
      patients in these four wards. This isolate was genotypically unrelated to the
      bacterial strain found in the three other patients in the neonatology ward.
      Interestingly, one patient in the neonatology ward harbored these two
      genotypically different strains. Finally, the patient in the intensive care unit
      was colonized with a different strain. We find ribotyping to be a more reliable
      technique than biochemical typing. The results of ribotyping are more easily
      interpreted than are those of total DNA analysis, with an equivalent degree of
      discrimination.

PMID- 1354223
TI  - DNA polymorphisms in methicillin-susceptible and methicillin-resistant strains of
      Staphylococcus aureus.
AB  - Restriction fragment length polymorphisms in methicillin-susceptible and
      methicillin-resistant (MRSA) strains of Staphylococcus aureus isolated in the
      same hospital over a 4-month period were studied by using SmaI and ApaI digestion
      of genomic DNA and pulsed-field gel electrophoresis. Each of the 20 methicillin
      susceptible strains had a unique SmaI pattern, but the 27 MRSA strains showed
      only seven SmaI patterns. More than half of the SmaI fragments in all of these
      seven patterns were identical, as were those in the patterns from two unrelated
      MRSA strains. Digestion with ApaI, which cuts staphylococcus DNA into at least
      twice as many fragments, confirmed the results obtained with SmaI. Lastly, the
      plasmid contents of MRSA strains showing identical SmaI and ApaI electrophoretic
      patterns were not identical. These results are interpreted as supporting the
      hypothesis that all MRSA strains arose from a single clone and emphasize the need
      to use several methods in epidemiological investigations of MRSA outbreaks.

PMID- 1354224
TI  - Typing of Histoplasma capsulatum by restriction fragment length polymorphisms in
      a nuclear gene.
AB  - We previously described yps-3, a Histoplasma-specific nuclear gene probe useful
      in the identification of Histoplasma capsulatum. By using restriction fragment
      length polymorphisms (RFLPs) of DNA detected by the yps-3 gene and mitochondrial
      DNA, 76 clinical and soil isolates of H. capsulatum were classified. The majority
      of North American isolates obtained from endemic regions of the midwestern United
      States were members of the previously characterized class 2, although four
      clinical isolates from different patients with AIDS from that region were grouped
      in class 1 with the temperature-sensitive Downs strain. A Florida soil isolate
      (FLS1) was placed in class 4 on the basis of RFLP with both probes. Two American
      Type Culture Collection strains (G184B and G186B) from Panama were grouped into
      class 3 by this analysis. A group of five H. capsulatum isolates obtained from
      patients with AIDS in New York City were typed into a new class 5 on the basis of
      yps-3 polymorphisms; those organisms fell into two broad mitochondrial DNA
      patterns, designated 5b and 5c. Two new isolates from Panama were also members of
      this broad yps-3 class 5 group, but they exhibited a distinct mitochondrial DNA
      profile (class 5a). A sixth class was detected in DNA obtained from a patient
      with AIDS from Panama; that DNA had unique RFLP profiles with respect to both
      probes. These observations suggest that the Histoplasma-specific yps-3 gene probe
      is a sensitive tool for typing H. capsulatum in clinical specimens. Additionally,
      these studies provide molecular support for the hypothesis that AIDS-associated
      histoplasmosis in nonendemic areas is due to reactivation of a previously
      acquired infection.

PMID- 1354226
TI  - The effects of cetirizine on the adhesion of human eosinophils and neutrophils to
      cultured human umbilical vein endothelial cells.

PMID- 1354225
TI  - Inhibitory effect of cetirizine on the bronchial eosinophil recruitment induced
      by allergen inhalation challenge in allergic patients with asthma.
AB  - In patients with asthma there is a recruitment of eosinophils in bronchoalveolar
      lavage fluid (BALF) after the late asthmatic reaction (LAR). Cetirizine is a
      selective H1 antagonist that inhibits the eosinophil recruitment induced by
      allergen in the skin. The aim of this study was to evaluate whether cetirizine
      was able to inhibit the LAR-induced inflammatory reaction. Twelve allergic
      asymptomatic subjects with asthma (aged 18 to 58 years) without any treatment
      were enrolled in the study; FEV1 was greater than 83% predicted in each case. An
      allergen inhalation-challenge test was performed to assess the presence of an
      LAR. In a double-blind, randomized, placebo-controlled study, the patients were
      treated for 8 days with either cetirizine, 15 mg twice a day (six patients, group
      1), or placebo (six patients, group 2). On day 8, a second allergen inhalation
      challenge test with the same allergen was performed, and BAL was realized 24
      hours later; as usual 250 ml of saline was instilled by 50 ml aliquots, and the
      first recovery was analyzed separately. In each case, the LAR observed after
      treatment was similar to the first one. In placebo-treated patients, an increased
      number of cells, mainly eosinophils, was observed in the first recovery of BALF
      compared with the number in subsequent recoveries. These numbers were
      significantly higher than numbers observed in cetirizine-treated patients.
      Cetirizine did not modify significantly the allergen inhalation-challenge test,
      but it inhibited the recruitment of inflammatory cells, mainly eosinophils.

PMID- 1354227
TI  - In vivo growth hormone (GH) response to human GH-releasing factor (GRF) or
      somatostatin (SRIF) in foetal pigs.
AB  - The short-term effect of hypothalamic GRF and SRIF on the pituitary release of GH
      at different stages of gestation has been studied. In the present experiment
      eighteen gilts were used, six at each of 66, 88 and 110 days of gestation.
      Ventral laparotomy was performed under general anaesthesia and a section of
      uterus was exteriorized. Blood samples were obtained from the umbilical vein of
      three foetuses per gilt just prior to the injection of each foetus with either
      saline, 5 micrograms/kg of hGRF (1-44)NH2 or 50 micrograms/kg of SRIF into the
      umbilical vein. Additional blood samples were obtained 15, 30, 45 and 60 min post
      injection. Serum samples were radioimmuno-assayed for GH (porcine). There was a
      treatment by gestational age interaction (P less than 0.01) on mean GH
      concentrations, area under the GH curve and GH peaks. While treatments had no
      effect (P greater than 0.1) on GH variables at 66 days of gestation, the area
      under the GH curve was slightly increased by GRF (P = 0.14) at day 88 and all GH
      variables were significantly increased (P less than 0.01)) by GRF at 110 days of
      gestation. There was a quadratic effect of time post-injection on GH
      concentrations at 88 (P less than 0.05) and 110 (P less than 0.001) days of
      gestation. There was no effect of SRIF injection (P greater than 0.1) on GH
      concentrations at any gestational age. In conclusion, the foetal pituitary
      responsiveness to GRF develops with foetal age and is maximal at the end of
      gestation, whereas there is no short-term response to a bolus of SRIF at any
      stage of gestation.

PMID- 1354228
TI  - Diseases of the intestine mimicking Crohn's disease.
AB  - We describe five patients who were initially thought to have Crohn's disease and
      were treated accordingly. The original diagnosis was based upon clinical
      presentation, roentgenograms, and histological examination, but subsequent follow
      up showed that diagnosis to be in error. The following diagnoses were established
      instead: tuberculosis, Actinomyces Israeli infection, reaction to gold therapy,
      metastatic cancer, and linitis plastica. We stress the importance of considering
      conditions that can mimic Crohn's disease.

PMID- 1354229
TI  - Altered IFN-gamma and IL-4 pattern lymphokine secretion in mice partially
      depleted of CD4 T cells by anti-CD4 monoclonal antibody.
AB  - Complete elimination of CD4 cells by in vivo treatment with anti-CD4 mAb may
      result in B cell polyclonal activation. Additionally, mice treated with doses of
      anti-CD4 that eliminate half the CD4 cells produced higher anti-SRBC antibody
      responses than controls. This suggests that partial CD4 depletion enhances Th2
      like function. To test this hypothesis we examined Th1 and Th2 lymphokine
      potential in mice partially depleted of CD4 cells. We measured IL-4 and IFN-gamma
      secretion by stimulated unfractionated spleen cells and analyzed activated,
      purified CD4 cells by RNA in situ hybridization to determine the percentage of
      IFN-gamma- or IL-4-producing cells. Unfractionated splenocytes from partially CD4
      depleted mice secreted more IL-4 and less IFN-gamma than splenocytes from control
      mice. In situ hybridization proved that CD4 cells from partially depleted mice
      contained a higher percentage of IL-4 and a lower percentage of IFN-gamma
      producing cells than controls. These results indicate that treatment with a dose
      of mAb resulting in partial CD4 depletion may permit increased Th2-like
      lymphokine expression. This study also provides evidence that cells committed to
      Th2-like function exist in vivo in mice.

PMID- 1354230
TI  - In vivo induction of apoptosis in immature thymocytes by staphylococcal
      enterotoxin B.
AB  - Staphylococcal enterotoxins are potent T cell mitogens. Recent studies have shown
      that the binding of these toxins to class II MHC molecules on accessory cells is
      essential for the stimulation of T cells which bear specific V beta segment of
      TCR. In the present study we show that i.v. administration of staphylococcal
      enterotoxin B (SEB) results in an enlargement of spleen and lymph nodes but
      causes thymus atrophy. Elimination of CD4+CD8+ cells predominantly accounted for
      the shrinkage of thymus, and the lowest level of this cell population was reached
      4 days after SEB injection. Furthermore, this decrease in CD4+CD8+ cells was
      accompanied by a relative increase in the percentages of CD4+CD8-, CD4-CD8+ and
      CD4-CD8- cells, whereas their absolute numbers actually reduced on day 4. The
      thymus shrinkage involved apoptosis which was characterized by DNA fragmentation
      and morphologic changes. The depletion of Thy-1 high, TCR-alpha beta low and TCR
      alpha beta intermediate cells also occurred with a kinetic correlated to the
      reduction of CD4+CD8+ cells. Our results further showed that the percentages of V
      beta 8+ cells reduced 12 h post SEB injection, increased after 2 days, and
      decreased again thereafter. SEB thus causes both apoptotic and stimulative
      effects in the thymus. Apparently, the tremendous loss of double-positive cells
      (greater than 90% in cell number on day 4) is not simply due to the reduction of
      V beta 8+ cells, the possible modulatory effect of other factors or hormones
      which may play a role in the cell death is discussed.

PMID- 1354231
TI  - Participation of the CD27 antigen in the regulation of IL-2-activated human
      natural killer cells.
AB  - The CD27 Ag is expressed by the majority of resting T lymphocytes and appears to
      play a crucial role in T cell activation. We found that some resting peripheral
      blood NK cells also express CD27. Furthermore, CD27 expression was up-regulated
      on NK cells stimulated by IL-2. The cytolytic activity of IL-2-activated, but not
      resting, NK cells was inhibited by an anti-CD27 mAb (anti-1A4). However, anti-1A4
      did not affect conjugate formation between IL-2-activated NK cells and tumor cell
      targets. In contrast, anti-1A4 inhibited CD2-mediated calcium mobilization and
      the serine esterase activity of NK cell granules. These inhibitory effects could
      be mediated in part by increase in intracellular cAMP levels induced by anti-1A4.
      Our results suggest that the CD27 Ag plays an important role in the regulation of
      activated NK cells.

PMID- 1354232
TI  - CD2 triggering stimulates the formation of platelet-activating factor-acether
      from alkyl-arachidonoyl-glycerophosphocholine in a human CD4+ T lymphocyte clone.
AB  - A human CD4+ T lymphocyte clone synthesized platelet-activating factor (PAF)
      acether when stimulated via the CD2 pathway. PAF-acether was characterized by
      biochemical and biophysical properties and precursor-product relationships (alkyl
      acyl-sn-glycero-3-phosphocholine (GPC)----alkyl-lyso-GPC (lyso-PAF)----PAF
      acether) were demonstrated. The clone contained substantial amounts of alkyl-acyl
      GPC. i) Hydrolysis of alkyl-acyl-GPC upon CD2 stimulation was evidenced:
      [3H]alkyl-lyso-GPC was formed from [3H]alkyl-acyl-GPC in [3H] alkyl-labeled
      cells; alkyl-lyso-GPC production was also bioassayed after CD2 triggering. ii)
      The rate of arachidonate transfer from diacyl-GPC to alkyl-acyl-GPC increased
      after CD2 stimulation of the [3H]arachidonate-labeled P28D T cells, demonstrating
      alkyl-lyso-GPC formation. iii) Comparison of the molecular species of the
      produced PAF-acether with those of arachidonate-containing alkyl-acyl-GPC raises
      the possibility that the produced PAF-acether is related to alkyl-arachidonoyl
      GPC.

PMID- 1354233
TI  - Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T
      cells.
AB  - The role and interdependence of CD8+ and CD4+ alpha beta-T cells in the acute
      response after respiratory infection with the murine parainfluenza type 1 virus,
      Sendai virus, has been analyzed for H-2b mice. Enrichment of CD8+ virus-specific
      CTL effectors in the lungs of immunologically intact C57BL/6 animals coincided
      with the clearance of the virus from this site by day 10 after infection. Removal
      of the CD4+ T cells by in vivo mAb treatment did not affect appreciably either
      the recruitment of CD8+ T cells to the infected lung, or their development into
      virus-specific cytotoxic effectors. In contrast, depletion of the CD8+ subset
      delayed virus clearance, although most mice survived the infection. Transgenic H
      2b F3 mice homozygous (-/-) for a beta 2 microglobulin (beta 2-m) gene
      disruption, which lack both class I MHC glycoproteins and mature CD8+ alpha beta
      T cells, showed a comparable, delayed clearance of Sendai virus from the lung.
      Virus-specific, class II MHC-restricted CTL were demonstrated in both freshly
      isolated bronchoalveolar lavage populations and cultured lymph node and spleen
      tissue from the beta 2-m (-/-) transgenics. Treatment of the beta 2-m (-/-) mice
      with the mAb to CD4 led to delayed virus clearance and death, which was also the
      case for normal mice that were depleted simultaneously of the CD4+ and CD8+
      subsets. These results indicate that, although classical class I MHC-restricted
      CD8+ cytotoxic T cells normally play a dominant role in the recovery of mice
      acutely infected with Sendai virus, alternative mechanisms involving CD4+ T cells
      exist and can compensate, in time, for the loss of CD8+ T cell function.

PMID- 1354234
TI  - Divalent cation substitution reveals CD18- and very late antigen-dependent
      pathways that mediate human neutrophil adherence to fibronectin.
AB  - We investigated the mechanisms by which Mn2+ alters human neutrophil (PMN)
      adherence to various connective tissue proteins. Substitution of Mn2+ for Ca2+
      and Mg2+ significantly increased adhesion of human PMN to plastic well coated
      with fibronectin, fibrinogen, and laminin but not gelatin. Anti-CD18 mAb almost
      completely blocked adherence to laminin, partly blocked adherence to fibrinogen,
      but did not inhibit adhesion to fibronectin at all. In contrast, anti-very late
      antigen (VLA)-5 mAb antibodies significantly reduced Mn(2+)-mediated PMN
      adherence to fibronectin, but not to laminin or fibrinogen, demonstrating that
      VLA-5-mediated PMN adherence to fibronectin, but not to fibrinogen or laminin.
      This was supported by experiments in which synthetic GRGDSP peptide significantly
      inhibited Mn(2+)-mediated adherence to fibronectin, but not to laminin or
      fibrinogen. Activation of PMN with phorbol ester or C5a stimulated VLA-5-mediated
      adhesion to fibronectin, but the contribution of VLA-5 to the forces mediating
      adherence could only be detected when CD18 function was either blocked with mAb,
      or when CD18 was congenitally absent. VLA-5 mediated adhesion was also more
      transient than CD18-dependent adhesion. These data further confirm the presence
      of PMN VLA integrins and demonstrate that PMN VLA-5 contributes to stimulated PMN
      adherence to fibronectin.

PMID- 1354236
TI  - Differentiation-related changes in quantitative binding of immunomagnetic beads.
AB  - Experiments have been carried out to demonstrate that cell viability and
      phenotypic characteristics are not affected by exposure to constant magnetic
      fields or growth in the presence of Dynabeads. This paper also demonstrates that
      the changes in the surface concentration of the antigens, SSEA-1 (stage-specific
      embryonic antigen-1) and histocompatibility antigen (MHC H2-Db) during
      differentiation as determined by flow cytometric analysis, are mirrored by
      changes in the numbers of bound immunomagnetic particles (Dynabeads) targeted
      with monoclonal antibodies to these cell surface antigens. These results clearly
      indicate that the numbers of beads bound to cells reflect the numbers of specific
      surface antigens present on the cells.

PMID- 1354235
TI  - IL-4 controls the selective endothelium-driven transmigration of eosinophils from
      allergic individuals.
AB  - The mechanism leading to selective accumulation of eosinophils in allergic
      inflamed tissue is still unknown. In this article, transendothelial migration of
      circulating eosinophils from normal and allergic individuals is characterized by
      means of human umbilical vein endothelial cells cultivated on extracellular
      matrix from human fibroblasts. IL-4 pretreatment of these vascular constructs
      induced adherence and impressive layer penetration of eosinophils but not of
      neutrophils. For layer penetration, blood eosinophils from nonallergic donors
      needed in vitro priming by granulocyte/macrophage-CSF, IL-3, or IL-5. In
      contrast, freshly isolated blood eosinophils from a group of patients with atopic
      dermatitis spontaneously penetrated IL-4-activated vascular constructs. The here
      described selective pathway of eosinophil transmigration was 1) specifically
      induced by IL-4; 2) inhibited by the IL-4 specific, neutralizing mAb 8F12; and 3)
      dependent upon endothelial mRNA synthesis. Both eosinophil adherence and
      transmigration were present at an IL-4 concentration of 1 U/ml. The effect of
      endothelial preincubation with IL-4 culminated at 16 h and persisted up to 48 h.
      A linear increase of subendothelial accumulating eosinophils was observed within
      2 h, reaching almost 100% after 4 h of coincubation. From inhibition experiments
      using different mAb, we conclude that the integrins CD11a/CD18, CD11b/CD18, and
      very late Ag-4 (CDw49d/CD29) are involved in this selective pathway of eosinophil
      transmigration. Taken together, this study demonstrates a novel mechanism which
      allows in vitro or in vivo primed eosinophils to leave the vascular compartment
      without influencing emigration of neutrophils.

PMID- 1354237
TI  - Activation of human immunodeficiency virus by herpes simplex virus.
AB  - Heterologous viruses have been examined for their ability to accelerate the
      course of infection with the human immunodeficiency virus (HIV) type 1. In this
      study, ACH-2 cells persistently infected with HIV-1 exhibited augmented HIV-1
      replication as a result of superinfection with herpes simplex virus (HSV) type 1.
      Using HSV-1 mutants with deletions in the genes encoding immediate-early proteins
      ICP0, ICP4, and ICP27, it was found that ICP0 and ICP27, but not ICP4, were
      essential for up-regulation of HIV replication. Northern blot analysis showed
      that this activation of HIV was characterized by an initial rise in the level of
      the small, subgenomic (2.0 and 4.3 kb) mRNA species, followed by an increase in
      the level of unspliced genomic (9.2 kb) mRNA. Such a shift in transcriptional
      phase recapitulates the early-to-late transition seen in single-step growth
      curves of acute HIV-1 infection. Thus, HSV can activate HIV-1 from latency in ACH
      2 cells, this activation of HIV is independent of productive HSV replication
      since the delta ICP4 deletion mutant is replication-incompetent, and this
      activation is evident as an increase in the steady-state levels of HIV
      transcripts.

PMID- 1354238
TI  - [Role of p185c-erbB2 in endometrial cancer growth in vitro].
AB  - Human endometrial adenocarcinoma cells (Ishikawa line) constitutively express c
      erbB2 coded oncoprotein p185erbB2 (p185) which is believed to be an orphan
      receptor for an unknown growth factor. Since we have shown that expression of
      p185 in primary lesions of endometrial cancer correlates well with high frequency
      of lymph node++ metastases and that the metastatic cells in the nodes strongly
      expressed p185, the role of the oncoprotein in processes of metastases was
      studied. Culturing the cells in the presence of 15% FCS and with monoclonal
      antibody to the extracellular domain of p185 (CB-1) inhibited cell growth and
      attenuated p185 expression on Western blotting, whereas no change occurred with
      the control antibody. Cells cultured without FCS achieved only approximately 1/3
      growth compared to cells with FCS, and further suppression of growth was observed
      after adding CB-1. When cells were cultured on human term amnion, basement
      membrane invasion with p185 expression was observed. In nude mice,
      intraperitoneal seeding resulted in implant formation which was also associated
      with positive p185 as well as cyclin immunohistochemistry. In the two
      experiments, treatment of cells with CB-1 inhibited invasion or implant
      formation. The present study suggests that a signal through p185 receptor
      molecules acts as a trigger for early proliferation, and interaction with the
      host may enhance up-regulation of p185.

PMID- 1354239
TI  - [A new method for diagnosis of amniotic fluid embolism by means of monoclonal
      antibody TKH-2 that recognizes mucin-type glycoprotein, a component in meconium].
AB  - Five monoclonal antibodies (moABs TKH-2, MA54, MA61, B72.3, and CC49), directed
      toward the O-linked mucin-type glycoprotein, showed signs of specific reactivity
      with human meconium. The reactivity of these moABs with meconium extract was
      examined by solid-phase ELISA with different native and sialidase-treated
      glycoproteins. All moABs react with meconium extract, whereas the reactivities of
      TKH-2, MA54, and MA61 are sialidase sensitive and the reactivity of TKH-2 with
      meconium extract was only inhibited by ovine submaxillary mucin (OSM), indicating
      that TKH-2 is the most sensitive and specific antibody clearly directed to the
      sialyl Tn antigen in meconium. The possible application of TKH-2 to diagnose
      amniotic fluid embolism (AFE) has been prelimiarily investigated. We demonstrated
      that the concentration of sialyl Tn antigen in the serum of patients with AFE was
      significantly increased, indicating that meconium was released into the maternal
      circulation. Our method for detecting sialyl Tn antigen in the serum of AFE
      patients is a direct way to demonstrate the release of meconium into the maternal
      circulation, and is a simple, rapid, non-invasive and sensitive method for the
      diagnosis of AFE.

PMID- 1354240
TI  - [Molecular constitution of human arylsulfatase A and its alteration in cancer].
AB  - Arylsulfatase A (ASA) was purified from human placenta, ovary, and ovarian cancer
      tissue. The purified ASA was composed of three non-identical peptides of 58 kDa,
      50 kDa, and 10 kDa on polyacrylamide gel electrophoresis in the presence of SDS
      (SDS-PAGE). The N-terminal sequence of the 58 kDa peptide was found to be
      identical with that of the 50 kDa on analysis with a protein sequencer. The
      peptide map of the 58 kDa peptide was quite similar to that of the 50 kDa except
      for some peaks. The 50 kDa peptide lacked the peptide from the residue Val445 to
      the C-terminus of the amino acid sequence deduced from the ASA cDNA. Four
      different peptides yielded by the 10 kDa peptide on HPLC had sequences near the C
      terminal side. These results suggest that the 50 kDa peptide and the 10 kDa
      peptide are yielded by the same peptide as the 58 kDa peptide on proteolytic
      processing. Ovarian ASA showed the same pattern on SDS-PAGE as placental ASA.
      Ovarian cancer ASA was mainly composed of the 58 kDa band, and in addition the 50
      kDa band decreased. The carbohydrate chain of ovarian cancer ASA was more
      resistant to endo-beta-N-acetylglucosaminidase H than that of normal ovary. These
      finding suggest that the processing of both the oligosaccharide chains and the
      protein unit is modified in ovarian cancer.

PMID- 1354241
TI  - Long-term excess of endogenous calcitonin in patients with medullary thyroid
      carcinoma does not affect bone mineral density.
AB  - In a cross-sectional study of 39 patients with medullary thyroid carcinoma (MTC),
      we have investigated the effects of long-term calcitonin excess on bone mineral
      density. Bone mineral density was measured by dual X-ray absorptiometry at the
      lumbar spine between the second and fourth vertebra and by single photon
      absorptiometry at the distal forearm. The mean observation time of each patient
      between diagnosis of tumour and measurement of bone mineral density was 62.4
      months (range 1-158 months). The mean calcitonin serum level was 14.4
      micrograms/l at the time of measurement of bone mineral density. All patients
      were substituted with 150-200 micrograms L-thyroxine daily. At both sites, the
      mean bone mineral densities of all patients with MTC were not significantly
      different from controls. Patients with normal calcitonin levels (below 0.2
      micrograms/l) after treatment had a normal bone mineral density of the spine but
      significantly (P less than 0.05) reduced bone mineral density values of the
      forearm. This was due to the decreased body surface areas of patients in this
      subgroup. Patients with multiple endocrine neoplasia type IIa had significantly
      higher bone mineral densities. Other bone-influencing factors, such as
      postoperative hypoparathyroidism, calcium intake, diarrhoea, menopause, tumour
      stage, previous anti-tumour treatment, or thyroxine substitution dose, did not
      affect bone mineral density. We thus conclude that long-term excess of endogenous
      calcitonin in patients with MTC has no positive effect on bone mineral density.

PMID- 1354242
TI  - The alpha chain gene of H-2O has an unexpected location in the major
      histocompatibility complex.
AB  - A previously unknown major histocompatibility complex class II molecule
      consisting of the beta chain encoded by the H-2Ob gene and an unknown alpha chain
      was recently described. We now report that the alpha chain occurs in two allelic
      forms distinguished by charge difference. Using inbred recombinant mouse strains
      we were able to map the H-2Oa gene to a location between the A.TL and B10.MBR
      recombination points. Cosmids covering this region were used to isolate the gene.
      Sequence analysis revealed that the H-2Oa gene is the murine equivalent of the
      human HLA-DNA gene. These results indicate that the human HLA-DNA gene, the
      existence of which has long been known, is indeed coding for DO alpha, the alpha
      chain pairing with DO beta.

PMID- 1354243
TI  - Evidence for an alpha/beta T cell-independent mechanism of resistance to
      mycobacteria. Bacillus-Calmette-Guerin causes progressive infection in severe
      combined immunodeficient mice, but not in nude mice or in mice depleted of CD4+
      and CD8+ T cells.
AB  - Depleting thymectomized mice of CD4+ T cells, or CD4+ plus CD8+ T cells, rendered
      them incapable of resolving Bacillus-Calmette-Guerin (BCG) infection in their
      lives, spleens, kidneys, and lungs. However, it did not render them incapable of
      stabilizing infection in the latter three organs after an initial period of BCG
      growth. Athymic nude mice showed a similar capacity to control BCG growth in
      these organs after a certain stage of infection. In contrast, congenitally severe
      combined immunodeficient (SCID) mice appeared to offer no resistance to BCG
      infection, in that the organism grew progressively in all organs of these mice
      and was lethal for them beginning on day 55 of infection. The results suggest
      that, although CD4+ T cells are important for resolving BCG infection, an
      alpha/beta T cell-independent mechanism of resistance can be acquired at 2-3 wk
      of infection that is capable of inhibiting further BCG growth in all organs
      except the lungs. Because this mechanism is absent from SCID mice, it is likely
      that it depends on the functions of gamma/delta T cells, B cells, or both types
      of cells. In keeping with this possibility is the additional finding that SCID
      mice engrafted with lymph node cells depleted of CD4+ or CD8+ T cells were
      capable of expressing an appreciable level of resistance against BCG infection.

PMID- 1354244
TI  - Mechanism of the rejection of major histocompatibility complex class I-disparate
      murine skin grafts: rejection can be mediated by CD4+ cells activated by allo
      class I + II antigen in CD8+ cell-depleted hosts.
AB  - In the preceding article, we analyzed the immunohistochemical rejection mechanism
      of major histocompatibility complex (MHC) class I (H-2K)-disparate murine skin
      grafts, and showed that only CD8+ cells infiltrated at the site of the epithelial
      tissue of MHC class I-disparate graft. We also showed that perfect survival of
      MHC class I-disparate grafts were attained in thymectomized recipients treated
      with anti-Lyt-2 monoclonal antibody. In this report, we showed that these long
      surviving allo-class I grafts were rejected in the absence of CD8+ cells by
      stimulation with allo-MHC class I + II-disparate graft as the second stimulation.
      Furthermore, it was immunohistochemically revealed that under that condition, a
      large number of CD4+ cells infiltrated into the epithelial tissue of these long
      surviving class I grafts, which were going to be rejected 2-5 d after the
      transplantation of a second graft with MHC class I + II difference. This result
      directly shows that CD4+ cells are able to became effectors for the rejection of
      allo-MHC class I (H-2K) skin graft.

PMID- 1354245
TI  - Discussion of "Effects of presumptive test reagents on the ability to obtain
      restriction fragment length polymorphism (RFLP) patterns from human blood and
      semen stains".

PMID- 1354246
TI  - Evaluation of four deoxyribonucleic acid (DNA) extraction protocols for DNA yield
      and variation in restriction fragment length polymorphism (RFLP) sizes under
      varying gel conditions.
AB  - This study originated from discussions and recommendations of the Technical
      Working Group on DNA Analysis Methods (TWGDAM). Four bloodstain deoxyribonucleic
      acid (DNA) extraction protocols and five semen stain DNA extraction protocols
      were evaluated. Nine laboratories participated in the extraction of DNA from 20
      bloodstains and 20 semen stains using each protocol. All blood and semen stains
      originated from a single donor and were prepared under uniform conditions to
      permit the direct comparison of DNA yields and restriction fragment lengths. The
      extracted DNA from approximately 600 bloodstains and 700 semen stains was
      quantified by yield gel analysis and a slot blot hybridization technique. The
      extracted DNA was digested and restriction fragment length polymorphism (RFLP)
      patterns were generated using three single-locus probes. The RFLP sizing data
      produced from the blood and semen stains were evaluated with respect to (1) DNA
      extraction method, (2) gel length, (3) agarose type, (4) presence or absence of
      ethidium bromide in the gel, and (5) fragment sizes obtained from DNA isolated
      directly from the donor's liquid blood. This study demonstrates conclusively that
      high-molecular-weight DNA can be isolated using either organic or nonorganic DNA
      extraction protocols and that the resulting RFLP sizes are highly reproducible
      regardless of gel length, agarose type, or presence/absence of ethidium bromide.

PMID- 1354247
TI  - Application of Empore C-8 extraction disks for screening urine in systematic
      toxicological analysis.
AB  - Solid-phase extraction (SPE) by means of disposable columns has become a widely
      accepted technique for sample pretreatment in toxicology, both for directed
      analyses and for screening analyses. However, the sample capacity in SPE is
      usually limited to a few millilitres. Therefore, we have investigated to what
      extent these problems can be overcome by using Empore extraction disks,
      consisting of chemically modified C-8 reversed-phase silica, embedded in an inert
      polytetrafluoroethylene (PTFE) matrix. Human urine was selected as the matrix and
      dexetimide and mepyramine were initially used as test drugs because these drugs
      were available in tritiated form. Additional drugs investigated included codeine,
      hexobarbital, imipramine, methamphetamine, and nitrazepam. In these
      investigations, the sample capacity for untreated urine was at least 25 mL, and
      analyte quantities up to 250 micrograms could be retained by these filters.
      Washing with water/methanol mixtures was successful in removing substantial
      amounts of endogenous interferences, and methanol proved to be an acceptable
      eluent. Thus, these disks seem to have interesting potential for toxicological
      analysis in that sample concentration and cleanup can be achieved at the same
      time.

PMID- 1354248
TI  - Effect of storage conditions on restriction fragment length polymorphism (RFLP)
      analysis of deoxyribonucleic acid (DNA) bound to positively charged nylon
      membranes.
AB  - The ability to generate an autoradiogram from deoxyribonucleic acid (DNA)
      immobilized on a positively charged nylon membrane could be compromised by the
      storage conditions of the membrane. HaeIII-digested human DNA was size
      fractionated and transferred to two types of positively charged nylon membranes.
      The membranes were stored at -20 degrees C, 4 degrees C, and ambient temperature
      and humidity for times ranging from 1 day to 13 weeks, then hybridized to
      variable number of tandem repeat (VNTR) probes to examine the effect of the
      storage conditions on the membrane-bound DNAs. It was shown that such membranes
      could be successfully hybridized and rehybridized if they were stored at -20 or 4
      degrees C, but storage under ambient conditions reduced or eliminated the
      likelihood of successful hybridization.

PMID- 1354249
TI  - Non-cast titanium restorations in fixed prosthodontics.
AB  - The problems encountered in casting titanium in dentistry have not been
      completely resolved. The Procera system forms crowns by means of a combination of
      spark-erosion and milling. The accuracy of fit was examined before and after
      ceramic veneering both in vitro and in vivo. Before veneering, on conical
      surfaces space widths were approximately 53 microns in vitro and 69 microns in
      vivo. At shoulders and occlusal surfaces, spaces of about 430 microns were
      measured in vitro and of about 500 microns were measured in vivo. After ceramic
      veneering, slight increases in space widths could be observed. The metal-ceramic
      compound was tested by the 3-point bending test (DIN) and the bending test (ISO).
      The DIN test was satisfactory, but not the ISO test. It is concluded that
      titanium crowns processed by the Procera System are suitable for clinical usage,
      if the space widths at shoulders and the occlusal surface and the special
      requirements of tooth preparation are taken into account.

PMID- 1354250
TI  - Synthesis and binding to beta-adrenergic receptors of p-aminobenzyl analogues of
      practolol and atenolol.
AB  - The p-aminobenzyl analogues (8a and 8b, respectively) of the cardioselective beta
      adrenergic receptor antagonists practolol and atenolol were prepared from the
      corresponding phenoxymethyloxiranes in 30 and 13% yields, respectively. The
      dissociation constants for the beta-adrenergic receptor were measured in membrane
      preparations of rat heart and lung. In membranes from the heart (which contain
      mostly beta 1-adrenergic receptors), the affinities of the derivatives and parent
      compounds were similar. By contrast, in membranes from the lung (which contain
      mostly beta 2-adrenergic receptors), the derivatives were more potent than the
      parent compounds. Thus, the cardioselectivities of the p-aminobenzyl analogues 8a
      and 8b were about one-sixth those of the respective parents.

PMID- 1354251
TI  - Characterization of the beta adrenoceptor subtype(s) mediating the positive
      inotropic effects of epinine, dopamine, dobutamine, denopamine and xamoterol in
      isolated human right atrium.
AB  - In patients with chronic heart failure cardiac beta-1 adrenoceptors are reduced,
      whereas beta-2 adrenoceptor changes vary depending on the etiology of the
      disease. Beta Adrenoceptor agonists can be used for short-term inotropic support
      in chronic heart failure; their clinical efficacy might depend on which beta
      adrenoceptor subtype(s) mediates their positive inotropic effect. Thus, the beta
      adrenoceptor subtype(s) involved in the positive inotropic effects of clinically
      used beta adrenoceptor agonists was characterized on isolated electrically driven
      human right atria by the use of the selective beta-1 adrenoceptor antagonist CGP
      20712 A (300 nmol/l) and/or the selective beta-2 adrenoceptor antagonist ICI
      118,551 (30 nmol/l). Epinine evoked positive inotropic effects through
      stimulation of beta-1 and beta-2 adrenoceptors to about the same degree, whereas
      dobutamine acted mainly at beta-1 adrenoceptors but had a significant beta-2
      adrenoceptor component. Both agonists were full agonists causing the same maximum
      increase in contractile force (Emax) as did isoprenaline or Ca++ (Emax = 1.0). In
      contrast, denopamine was a partial selective beta-1 adrenoceptor agonist (Emax =
      0.75-0.85). Dopamine was in the presence of uptake1-blockade (by 5 mumol/l
      phenoxybenzamine) a partial agonist (Emax = 0.60-0.70) acting selectively at beta
      1 adrenoceptors; in the absence of uptake1-blockade, however, dopamine was a full
      agonist, indicating that part of its positive inotropic effect is indirect via
      the release of endogenous noradrenaline. Xamoterol did not exert positive
      inotropic effects, but concentration-dependently slightly decreased basal force
      of contraction.

PMID- 1354252
TI  - An antagonist/partial agonist at the polyamine recognition site of the N-methyl-D
      aspartate receptor that alters the properties of the glutamate recognition site.
AB  - The effects of N-(3-aminopropyl)-1,10-diaminodecane (APDA10) on the N-methyl-D
      aspartate (NMDA) receptor/ion channel complex were investigated. In the presence
      of 100 microM glutamate and 100 microM glycine, APDA10 had biphasic effects on
      the binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten5,10-imin
      e (MK-801) to NMDA receptors on well washed synaptic plasma membranes. The
      maximal stimulation of binding by APDA10 was less than that seen with spermine.
      In the presence of glutamate and glycine, APDA10 attenuated the stimulatory
      effect of spermine and the inhibitory effect of 1,10-diaminodecane. In the
      nominal absence of glutamate and glycine, APDA10 had no effect on the binding of
      [3H]MK-801, but antagonized the stimulatory effect of spermine on the binding of
      [3H] MK-801. These data suggest that APDA10 acts as a mixed antagonist/partial
      agonist at the polyamine recognition site, and that the partial agonist
      properties of APDA10 are dependent on the activation state of the receptor
      complex. An increase in the potency of the glutamate site antagonists D-2-amino-5
      phosphonovaleric acid and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid
      for inhibiting the binding of [3H]MK-801 was seen in the presence of APDA10.
      APDA10 also increased the affinity of binding of [3H]3-(2-carboxypiperazin-4-yl)
      propyl-1-phosphonic acid to the NMDA receptor complex but had no effect on the
      binding of [3H]glycine. These data suggest that the polyamine APDA10 may alter
      the properties of the glutamate recognition site on the NMDA receptor complex.

PMID- 1354253
TI  - The behavioral pharmacology of olanzapine, a novel "atypical" antipsychotic
      agent.
AB  - Olanzapine (LY170053, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]
      benzodiazepine) is a novel "atypical" antipsychotic agent with 5
      hydroxytryptamine2.dopamine D1/D2 antagonist activity and anticholinergic
      properties. In behavioral studies, olanzapine (1.25-10 mg/kg, p.o.) antagonizes
      apomorphine-induced climbing behavior in mice, demonstrating that the compound
      possesses D1/D2 antagonist activity in vivo. Olanzapine (0.3-20 mg/kg, p.o.)
      antagonizes 5-hydroxytryptophan-induced head twitches in mice at doses much lower
      than those required to block the climbing response, confirming that in vivo, the
      compound is a more potent 5-hydroxytryptamine2 antagonist than dopamine
      antagonist. Olanzapine (2.5-10 mg/kg, p.o.) also antagonized oxotremorine-induced
      tremor in mice. In a conditioned avoidance paradigm in rats, olanzapine inhibits
      the avoidance response with an ED50 of 4.7 mg/kg p.o; however, unlike other
      antipsychotic agents, catalepsy is only observed at much higher doses (ED50 39.4
      mg/kg, p.o.). These data would suggest that the compound will be less likely to
      produce undesirable extrapyramidal symptoms. Unlike "typical" antipsychotics,
      olanzapine (1.25-5 mg/kg p.o.) increases responding during the conflict component
      of a modified Geller Seifter test, demonstrating that the compound may also
      possess anxiolytic activity. In another series of experiments, olanzapine (1.25
      mg/kg, i.p.) produced clozapine-appropriate responding in a drug discrimination
      model in which animals had been trained to discriminate clozapine (5 mg/kg, i.p.)
      from vehicle. On the basis of these results, it would therefore be predicted that
      olanzapine will have an atypical profile and will be less likely to induce
      undesirable extrapyramidal symptoms than currently available drugs.

PMID- 1354254
TI  - Parasympatholytic effects of vecuronium are mediated by nicotinic and muscarinic
      receptors in hearts of anesthetized dogs.
AB  - We investigated the blocking effects of vecuronium and pancuronium on the
      negative chronotropic and dromotropic responses to stimulation of the
      parasympathetic nerves in the anesthetized, open-chest dog. We stimulated the
      intracardiac parasympathetic nerves to the SA nodal region (SAP stimulation) or
      to the atrioventricular nodal region (AVP stimulation). SAP stimulation or AVP
      stimulation selectively decreased heart rate or increased atrioventricular
      conduction time, respectively. Vecuronium and pancuronium inhibited the
      chronotropic response to SAP stimulation and the dromotropic response to AVP
      stimulation in a dose-dependent manner. The ID50 of each drug for the dromotropic
      response was less than that for the chronotropic response. The blocking effect of
      vecuronium on the negative cardiac responses to parasympathetic stimulation was
      about 10-fold less potent than that of pancuronium. These results suggest that
      the blocking effects of vecuronium and pancuronium on the negative chronotropic
      and dromotropic responses to parasympathetic stimulation differ from those of
      atropine in the heart. In the isolated right atrium perfused with blood from the
      support dog, vecuronium, injected into the external jugular vein of the support
      dog, dose-dependently inhibited the negative chronotropic and inotropic responses
      to carbachol or SAP stimulation and the negative followed by positive
      chronotropic and inotropic responses to nicotine. The ID50 values for carbachol,
      nicotine and SAP stimulation were not significantly different. These results
      suggest that parasympatholytic effects of vecuronium are mediated by not only
      muscarinic receptors but also neuronal nicotinic receptors in hearts of
      anesthetized dogs.

PMID- 1354255
TI  - gamma-Glutamyltransferase-dependent biliary-hepatic recycling of methyl mercury
      in the guinea pig.
AB  - After secretion into bile, glutathione (GSH) and GSH-conjugates are catabolized
      by gamma-glutamyltransferase (gamma-GT) and dipeptidases yielding glutamate,
      cysteine, glycine and cysteine S-conjugates, and these products are then
      partially reabsorbed from the biliary tree. Because methyl mercury is thought to
      be secreted into bile as a GSH- complex, it may be subject to a similar
      intrahepatic cycle, thus delaying its elimination. To examine this possibility
      guinea pigs were dosed with 203Hg-methyl mercury (10 mumol/kg i.v.), followed by
      a retrograde intrabiliary infusion of Krebs-Henseleit buffer (control) or
      acivicin (an inhibitor of gamma-GT). Acivicin increased biliary excretion of
      203Hg by 41%, and GSH from 0.14 +/- 0.10 to 2.02 +/- 0.26 nmol/min.g of liver.
      Bile analyzed by gel filtration chromatography revealed that CH(3)203Hg-GSH
      accounted for most of this increased 203Hg excretion. When CH(3)203Hg-complexes
      of GSH, cysteine and albumin were introduced directly into the biliary tree by
      retrograde infusion, 203Hg recovery in bile was significantly lower than recovery
      of the nonabsorbable marker [14C]sucrose, ranging from 26.0 +/- 2.9% for
      CH(3)203Hg-cysteine to 48.7 +/- 5.1% for CH(3)203Hg-albumin and approximately 60%
      for [14C]sucrose. Acivicin pretreatment significantly increased 203Hg excretion
      into bile after retrograde infusion of CH(3)203Hg-GSH, whereas 203Hg recovery
      after retrograde infusion of CH(3)203Hg-cysteine remained constant.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1354256
TI  - Poly-L-aspartic acid does but triiodothyronine does not protect against
      gentamicin-induced cytotoxicity in the porcine kidney cell line LLC-PK1.
AB  - This study investigated the protective effect of thyroid hormone and poly-L
      aspartic acid (PAA) in an in vitro model of gentamicin nephrotoxicity. LLC-PK1
      porcine renal cells were grown in Medium 199 supplemented with either fetal
      bovine serum or thyroid hormone-depleted fetal bovine serum. After a
      preincubation with or without 30 nM L-triiodothyronine for 3 days, or 0.1 mM PAA
      for 1 hr, cells were coincubated with 1 mM gentamicin for an additional 3 days.
      Determinations were made of the following indicators of cell damage and/or
      viability: the numbers of detached dead cells, the total lactate dehydrogenase
      activity and its percentage release and gamma-glutamyl transpeptidase activity.
      Preincubation with L-triiodothyronine did not protect from gentamicin-induced
      cell death but did reduce cellular accumulation of gentamicin (3.2 +/- 0.8
      micrograms/mg of protein vs. 5.2 +/- 1.8 micrograms/mg of protein in controls; P
      less than .05). In contrast, preincubation with 0.1 mM PAA decreased gentamicin
      induced cell death (gentamicin: 685 +/- 416% of control dead cells and 487 +/-
      48% of control lactate dehydrogenase release; PAA + gentamicin: 164 +/- 63% of
      control dead cells and 257 +/- 85% of control lactate dehydrogenase release; P
      less than .05) but failed to attenuate inhibition by gentamicin of gamma-glutamyl
      transpeptidase activity (gentamicin: 69 +/- 7% of control; PAA+gentamicin: 76 +/-
      3% of control) and failed to alter cellular gentamicin levels. Protection against
      gentamicin nephrotoxicity by L-triiodothyronine was not demonstrated in LLC-PK1
      cells, indicating that its protective effect in vivo is likely due to a systemic
      effect of the hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354257
TI  - Comparison of the D1-dopamine agonists SKF-38393 and A-68930 in neonatal 6
      hydroxydopamine-lesioned rats: behavioral effects and induction of c-fos-like
      immunoreactivity.
AB  - Administration of the selective D1-dopamine receptor agonist 2,3,4,5-tetrahydro
      7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SKF-38393) to neonatal 6-hydroxydopamine
      lesioned rats results in profound behavioral manifestations and induction of
      striatal c-fos-like immunoreactivity. The full D1-dopamine agonist I,[R,S]1
      aminomethyl-3,4-dihydro-5,6-dihydroxy-3-phenyl-1H-2-benzopyran hydrochloride (A
      68930), like SKF-38393, produced a dose-dependent, D1-selective increase in
      locomotor activity and striatal c-fos-like immunoreactivity. These responses were
      antagonized by a D1-dopamine antagonist, but not by a D2-dopamine antagonist. A
      68930 produced locomotor activation at a lower dose than SKF-38393, but no dose
      of A-68930 was able to produce the magnitude of locomotor activation seen with
      SKF-38393. Both A-68930 and SKF-38393 induced similar stereotyped behaviors and
      possessed similar propensities to induce self-injurious behavior in neonatally
      lesioned rats; however, A-68930 was significantly more potent than SKF-38393 in
      inducing these behaviors. When either SKF-38393 or A-68930 were administered
      repeatedly at 2-week intervals, behavioral sensitization (priming) occurred.
      However, unlike SKF-38393, a high dose of A-68930 produced seizure activity and
      markedly desensitized D1-dopamine receptor activation for up to 3 days after
      administration. These results with A-68930 provide additional evidence that the
      specific behavioral and biochemical responses observed in neonatally lesioned
      rats after SKF-38393 administration are due to actions on D1-dopamine receptors,
      and indicate that A-68930 provides a new tool for investigating D1-dopamine
      receptor function.

PMID- 1354260
TI  - Effect of benzoyl peroxide on two-stage oral carcinogenesis and gamma-glutamyl
      transpeptidase in hamsters.
AB  - Hamster buccal pouches were treated with 7,12-dimethylbenz(a)anthracene (DMBA)
      triweekly for 3 wk and subsequently with 40% benzoyl peroxide (BP) in acetone for
      up to 27 wk. BP treatment resulted in a marked hyperplasiogenic effect and a weak
      tumor promoting effect. Whereas most carcinogens and tumor promoters induce gamma
      glutamyl transpeptidase (GGT) activity, BP diminished its activity as compared to
      controls. Comparable results have also been noted in the liver, where a group of
      newly isolated hepatocarcinogens, peroxisome proliferators (PP), also
      characteristically deplete the GGT activity and placental glutathione S
      transferase (GST-P), another tumor marker.

PMID- 1354258
TI  - Excitatory and inhibitory synaptic currents and receptors in rat medial septal
      neurones.
AB  - 1. A thin-slice preparation was used to study the postsynaptic potentials and the
      underlying currents of visually identified rat medial septal (MS) neurones under
      tight-seal voltage- and current-clamp conditions. 2. Upon stimulation of the
      afferent fibres, all MS neurones exhibited a sequence of excitatory-inhibitory
      postsynaptic potentials (EPSP-IPSP). Under voltage clamp, with potassium
      glutamate as internal solution and at negative holding potentials (Vh), this
      synaptic pattern appeared as an initial inward current followed by a longer
      lasting outward current. 3. The inward postsynaptic current was completely
      abolished by 5 microM-6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) whereas the
      outward current disappeared in the presence of 10 microM-bicuculline. Thus the
      major excitatory and inhibitory synaptic inputs were identified as being due to
      activation of quisqualate/kainate glutamatergic and gamma-aminobutyric acid
      (GABAA) receptors, respectively. 4. At positive Vh a CNQX-resistant component of
      the excitatory postsynaptic current (EPSC) was revealed. This component was
      slower than the one mediated by the quisqualate receptor and was abolished by 3
      3(2-carboxypiperazine-4-yl)propyl-1-phosphonate (CPP), indicating that N-methyl-D
      aspartate (NMDA) receptors are involved in excitatory synaptic transmission in MS
      cells. The existence of the two main subtypes (NMDA and non-NMDA) of
      glutamatergic receptors in MS neurones was also confirmed by the responses of the
      neurones to bath application of the different agonists (glutamate, quisqualate,
      kainate and NMDA). 5. The CNQX-sensitive EPSC had a reversal potential near 0 mV.
      The fast rise time (approximately 0.7 ms) indicates a somatic location of the
      excitatory synapses. The relaxation kinetics of the fast EPSC were fitted by a
      single exponential function with a time constant of 1.13 +/- 0.1 ms. This
      parameter was independent of Vh. Fast EPSCs were blocked by CNQX in a dose
      dependent manner (dissociation constant, KD = 0.2 microM). 6. Inhibitory
      postsynaptic currents (IPSCs) were studied in symmetrical chloride solutions
      after blockade of the excitatory receptors. The current-voltage relation was
      linear and reversed at 0 mV. The IPSCs had a fast rise time and their decay was
      best fitted by the sum of two exponentials with time constant of approximately 20
      and 50 ms (Vh = -60 mV). The IPSCs were abolished by bicuculline (KD = 1 microM),
      a selective antagonist of GABAA receptors. As expected, bath application of GABA
      produced large whole-cell currents. 7. In many cells, in addition to the usual
      EPSP-IPSP sequence, failures of either the EPSP or the IPSP were frequently
      observed during the experimental protocol.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1354259
TI  - Potassium channels opened by noradrenaline and other transmitters in excised
      membrane patches of guinea-pig submucosal neurones.
AB  - 1. Unitary potassium currents were recorded in outside-out patches of membrane
      from guinea-pig submucosal neurones. The actions of alpha 2-adrenoceptor
      agonists, somatostatin and [Met5]enkephalin were studied. 2. Three main groups of
      background potassium channels were active. At -70 mV with 160 mM-potassium on
      both sides of the membrane, they had conductances of 30-65 (small), 120-160
      (intermediate) and 220-260 pS (large). 3. The open channel current-voltage
      relation showed only constant-field rectification. Extracellular barium (2 mM)
      and caesium (2 mM) decreased inward but not outward currents. Tetraethylammonium
      (10 mM) had no effect. 4. Noradrenaline, somatostatin and [Met5]enkephalin each
      increased the open probability of all three classes of channel when two or more
      unitary amplitude channels were active in the membrane patch. Agonists were
      ineffective when no channel, or a single channel, was discernible in the patch.
      Agonists did not cause the appearance of unitary currents distinct from those
      seen prior to their application. 5. The effect of the agonists required
      intracellular guanosine 5'-triphosphate. 6. The results show that the
      hyperpolarization of submucosal plexus neurones by noradrenaline, somatostatin
      and [Met5]enkephalin results from the increased opening of at least three types
      of background potassium channel, and that the coupling from the receptors to the
      channels is maintained in excised membrane patches.

PMID- 1354261
TI  - An improved technique for processing an overdenture on implants.
AB  - This article shows an alternate procedure for making an overdenture on implants.
      This method helps to eliminate a chairside reline for the dentist by directly
      incorporating the clips into the heat-cured acrylic resin. The procedure is
      divided into three main sections. The first section deals with the impressions,
      casts, and records. The second section relates to the making of the bar, and the
      third section shows the assembling of the clips.

PMID- 1354262
TI  - Bar-retained overdentures for implants--technical aspects.
AB  - The principles of the laboratory procedures for making overdentures retained by
      bar abutments on ITI implant fixtures are described, and details of producing the
      master casts, making a soldered bar, and processing a prosthesis incorporating a
      cobalt-chromium alloy strengthener are given.

PMID- 1354263
TI  - Oxygen isosteric derivatives of 3-(3-hydroxyphenyl)-N-n-propylpiperidine.
AB  - Some substituted 3-phenylmorpholines (10a-e,j,k) and 3-thienylmorpholines
      (10f,g), isosteres of 3-(3-hydroxy-phenyl)-N-n-propylpiperidine (3-PPP), were
      prepared and submitted to binding assays on D-2 dopaminergic and 5-HT1 and 5-HT2
      serotonergic receptors, in comparison with 3-PPP and its analogue 3a,b. The
      results show the loss of D-2 affinity for all morpholines, while a certain
      activity was still observable for piperidine derivatives. Regarding the
      serotonergic affinity, only chloro and methoxy derivatives (10a-d) were
      moderately active on the 5-HT1A receptor, either when the substituent was in the
      C-2 or C-3 position, whereas no tested compounds showed affinity toward the 5-HT2
      receptor.

PMID- 1354264
TI  - Disodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino] propyl]-1,3
      benzodioxole-2,2-dicarboxylate (CL 316,243). A potent beta-adrenergic agonist
      virtually specific for beta 3 receptors. A promising antidiabetic and antiobesity
      agent.

PMID- 1354265
TI  - The Mammalian Myocardium. Biochemical and Physiological Mechanisms Underlying the
      Heartbeat. A 2nd International Symposium. Leeds, England, 26-29 July 1992.
      Abstracts.

PMID- 1354266
TI  - Phylogenetic analysis of the thiolase family. Implications for the evolutionary
      origin of peroxisomes.
AB  - The thiolase family is a widespread group of proteins present in prokaryotes and
      three cellular compartments of eukaryotes. This fact makes this family
      interesting in order to study the evolutionary process of eukaryotes. Using the
      sequence of peroxisomal thiolase from Saccharomyces cerevisiae recently obtained
      by us and the other known thiolase sequences, a phylogenetic analysis has been
      carried out. It shows that all these proteins derived from a primitive enzyme,
      present in the common ancestor of eubacteria and eukaryotes, which evolved into
      different specialized thiolases confined to various cell compartments. The
      evolutionary tree obtained is compatible with the endosymbiotic theory for the
      origin of peroxisomes.

PMID- 1354269
TI  - [Study on adrenergic acid secretion using isolated parietal cells of guinea
      pigs].
AB  - In order to investigate the effect of adrenergic nerve system on acid secretion
      at the cell-levels, acid secretion of isolated parietal cells stimulated by
      various adrenergic agonists was observed by measuring the accumulation of 14C
      aminopyrine (A.P.). Both isoproterenol, beta receptor agonist, and salbutamol,
      beta-2 receptor selective agonist, increased A.P. accumulation, whereas
      dobutamine, beta-1 receptor selective agonist, showed no effect. And beta-2
      receptor on parietal cells was detected by binding assay. These data may suggest
      that parietal cells have beta-2 receptors through which acid secretion will
      occur.

PMID- 1354267
TI  - Regulated adenovirus mRNA 3'-end formation in a coupled in vitro transcription
      processing system.
AB  - The adenovirus major late transcription unit encodes five poly(A) sites whose use
      during infection is regulated. Early in the infection, the 5'-most site, L1, is
      used preferentially, whereas late in infection, all sites are used equivalently.
      Previous in vivo experiments indicated that regulatory sequences flank the AAUAAA
      and GU-rich elements of the L1 poly(A) site. We have developed an in vitro
      coupled transcription-processing system for studying the function of these
      regulatory sequences in HeLa cell nuclear extracts. The in vitro analysis using
      this system shows that predominant use of the L1 poly(A) site, as mediated by the
      upstream regulatory sequence, is independent of transcription. Furthermore, the
      reaction conditions are favorable to both 3'-end processing and splicing, making
      this system generally useful for the study of posttranscriptional processes.

PMID- 1354268
TI  - Somatostatin in the management of gastrointestinal fistulas: a multicenter trial.

PMID- 1354270
TI  - Cell surface aminopeptidase A and N activities in human glomerular epithelial
      cells.
AB  - Cell surface aminopeptidases N (APN) and A (APA) have been characterized on
      cultured human glomerular epithelial cells and a SV40-transformed cell line
      derived from them. APN had a wide substrate specificity whereas APA only attacked
      peptides with an acidic N terminal amino acid. Both enzymes also differed by
      their sensitivity to divalent cations and to aminopeptidase inhibitors.
      Phorbolmyristate acetate (PMA) stimulated APN but not APA expression after a lag
      time of 12 hours. An increase of twice the basal value was observed with 10 ng.ml
      1 PMA. This effect was confirmed by immunofluorescence staining using a specific
      anti-APN monoclonal antibody. Both ecto- and total enzyme activities were
      stimulated by PMA. The effect of PMA was suppressed by H7, a PKC inhibitor, and
      cycloheximide, an inhibitor of protein synthesis. Thrombin (1 to 2.5 U.ml-1) and
      interferon (IFN)-gamma (100 U.ml-1) also stimulated APN activity, the latter
      after longer exposure of the cells. APA activity was increased by 8-bromo-cAMP
      and two cAMP-stimulating agents, forskolin and isobutylmethylxanthine (IBMX). A
      twofold increase above basal value was obtained with 100 microM forskolin after
      72 hours of treatment. cAMP-stimulated APA activity was suppressed by
      cycloheximide. Dexamethasone also stimulated APA activity. The effects of
      forskolin and dexamethasone were additive. These results demonstrate that APN and
      APA in glomerular epithelial cells are under different regulations: mitogens and
      IFN-gamma for APN, cAMP and glucocorticoids for APA. This selective expression
      may imply possible functional consequences in glomerular diseases.

PMID- 1354271
TI  - Tetranectin, a plasminogen kringle 4-binding protein. Cloning and gene expression
      pattern in human colon cancer.
AB  - BACKGROUND: Tetranectin is a recently discovered protein that binds to kringle 4
      region of plasminogen (Clemmensen I, Petersen LC, Kluft C. Eur J Biochem 1986;
      156:327. EXPERIMENTAL DESIGN: The mRNA encoding human tetranectin was cloned by
      using degenerate primers in a reverse transcriptase reaction followed by
      polymerase chain reaction amplification. The resulting polymerase chain reaction
      product was examined by DNA sequencing and subsequently used as probe for
      screening a human placental cDNA library. A full length cDNA clone (TET-1) was
      isolated, characterized, and used for Northern blot and in situ hybridization.
      RESULTS: DNA sequencing analysis revealed a 874-base pair cDNA containing an open
      reading frame of 606 base pairs encoding 202 amino acids. A classical signal
      peptide was present starting with the initiation methionine. The mature
      tetranectin chain consisted of 181 amino acids (M(r) = 20,169). The 3' noncoding
      region contained a single polyadenylation signal and a 26-residue poly A tail.
      The predicted amino acid sequence of the mature tetranectin chain showed, except
      for one amino acid, complete identity to that obtained by sequencing of the
      native protein (Fuhlendorff J, Clemmensen I, Magnusson S, Biochemistry
      1987;26:6757). Northern blot of poly A+ revealed a single band of approximately 1
      kb. Northern blot analysis of poly A+ isolated from a series of normal human
      tissues (lung, liver, spleen, kidney, and pancreas) revealed a distinct
      hybridization band that was especially prominent in the lungs and spleen. No
      hybridization signal was detected in three carcinoma cell lines examined in
      parallel. Northern blot analysis of poly A+ RNA isolated from solid tumors
      revealed a tetranectin specific mRNA band. In situ hybridizations on tissue
      sections of colon carcinomas and normal colon tissues revealed a strong and
      distinct hybridization signal of stromal cells in colon carcinomas but not in
      tumor cells. Only a few stromal cells were labeled in the normal colon.
      Immunohistochemically, tetranectin was found in a fibrillar-like pattern in the
      extracellular matrix around the tumor islands and was not detectable in the
      normal colon stromal tissue. Plasminogen exhibited a similar immunohistochemical
      staining pattern as tetranectin. CONCLUSIONS: Human tetranectin cDNA comprises
      874 base pairs including a 606-base pair open reading frame encoding 202 amino
      acids including a classical signal peptide. This protein is produced locally by
      cells of the stromal compartment of tumors and is deposited into the
      extracellular matrix. Since tetranectin binds to plasminogen we hypothesize that
      it could function as an anchor and/or reservoir for plasminogen and similar
      substances that regulate tumor invasion and metastasis as well as tumor
      angiogenesis.

PMID- 1354272
TI  - The use of radioreceptor assays for the determination of benzodiazepines in
      biological samples: a review.
AB  - Benzodiazepines are the most widely prescribed class of psychotropes. The
      demonstration of specific, high affinity binding sites for benzodiazepines in
      mammalian brain has provided a basis for a radioreceptor assay (RRA) of these
      compounds in biological samples (fluids or tissues). The RRA permits the
      simultaneous measurement of the benzodiazepine molecules that bind to the
      receptor, providing a total estimate of all pharmacologically active forms of the
      drug, which is useful in drug monitoring and in the intensive care of patients.
      After a complete description of the methodological aspects of this technique, the
      results obtained in therapeutic monitoring and in toxicological analysis are
      reviewed, and the advantages and disadvantages of this method are examined.

PMID- 1354273
TI  - Nursing's identity crisis.

PMID- 1354274
TI  - Prevention of serious cardiac events by low-dose aspirin in patients with silent
      myocardial ischaemia. The Research Group on Instability in Coronary Artery
      Disease in Southeast Sweden.
AB  - On exercise testing after an episode of unstable coronary artery disease (CAD;
      unstable angina or non-Q-wave myocardial infarction), a proportion of patients
      show ST-segment depression, indicating myocardial ischaemia, but do not report
      concomitant symptoms of angina. Treatment of such "silent" ischaemia aims mainly
      to reduce the risk of subsequent cardiac events. We have studied the effect of
      low-dose aspirin in patients with myocardial ischaemia defined at the
      predischarge test as silent (though patients might have had symptomatic ischaemia
      at other times) or symptomatic. 740 men with unstable CAD aged 70 years or less
      underwent symptom-limited exercise testing before hospital discharge; 144 showed
      ST depression without pain and 230 ST depression with simultaneous chest pain. Of
      the silent ischaemia group, 67 were randomly assigned placebo and 77 aspirin (75
      mg daily); the corresponding numbers in the symptomatic group were 125 and 105.
      Angina symptoms were less common in the silent than in the symptomatic ischaemia
      group both before inclusion and during follow-up, and a greater proportion of the
      silent ischaemia group were included because of myocardial infarction. In both
      ischaemia groups aspirin treatment reduced the risk of subsequent myocardial
      infarction or death by 3 months' follow-up (silent 4% of aspirin-treated vs 21%
      of placebo-treated patients, p = 0.004; symptomatic 9% vs 18%, p = 0.05); at 12
      months' follow-up a significant benefit of aspirin was still apparent in the
      silent ischaemia group (9% vs 28%, p = 0.005) but not in the symptomatic group
      (13% vs 22%, p = 0.109). Low-dose aspirin reduced the risk of subsequent
      myocardial infarction at least as well in silent as in symptomatic myocardial
      ischaemia. Since improvement of outlook is the main treatment objective in
      symptom-free patients, aspirin should be a mainstay of their treatment.

PMID- 1354275
TI  - Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion
      after curative resection for colorectal adenocarcinoma.
AB  - About half the patients treated with curative resection for colorectal cancer do
      not survive long-term. Adjuvant chemotherapy given during and after surgery may
      prevent hepatic metastases and improve patient survival. In patients with
      colorectal cancer, we have done a multicentre, randomised controlled trial
      comparing five-year survival after intraportal infusion of fluorouracil (1 g per
      day) plus heparin (10,000 U per day) (130 patients) or heparin alone (123) during
      curative resection and for 7 days thereafter, or after resection alone (145).
      There was no reduction in liver metastasis or increased overall survival
      advantage in either active-treatment arm of the study. However, patients who had
      stage III, Dukes' C (lymph-node-positive) tumours resected and were treated with
      fluorouracil plus heparin had a significant (p less than 0.03) survival advantage
      of about 16% compared with surgery-only controls. Further study of intraportal
      infusion of chemotherapeutic agent as adjuvant treatment to surgery in patients
      with colorectal cancer appears worthwhile.

PMID- 1354276
TI  - Effects of ribose on exercise-induced ischaemia in stable coronary artery
      disease.
AB  - There is no established treatment specifically aimed at protecting or restoring
      cardiac energy metabolism, which is greatly impaired by ischaemia. Even after
      reperfusion, myocardial content of ATP remains low for more than 72 h. Long-term
      post-ischaemic dysfunction and irreversibility of ischaemic damage have been
      associated with low ATP content. Evidence that the pentose sugar ribose
      stimulates ATP synthesis and improves cardiac function led us to test the
      possibility that ribose increases tolerance to myocardial ischaemia in patients
      with coronary artery disease (CAD). 20 men with documented severe CAD underwent
      two symptom-limited treadmill exercise tests on 2 consecutive days; we postulated
      that the ischaemia induced might bring about changes in ATP metabolism lasting
      for several days. Patients whose baseline tests showed reproducibility were
      randomly allocated 3 days of treatment with placebo or ribose 60 g daily in four
      doses by mouth. Exercise testing was repeated after treatment on day 5. At that
      time mean (95% confidence interval) treadmill walking time until 1 mm ST-segment
      depression was significantly greater in the ribose than in the placebo group (276
      [220-331] vs 223 [188-259] s; p = 0.002). The groups did not differ significantly
      in time to moderate angina. In the ribose-treated group the changes from baseline
      to day 5 in both time to ST depression and time to moderate angina were
      significant (p less than 0.005), but these changes were not significant in the
      placebo group. In patients with CAD, administration of ribose by mouth for 3 days
      improved the heart's tolerance to ischaemia. The presumed effects on cardiac
      energy metabolism offer new possibilities for adjunctive medical treatment of
      myocardial ischaemia.

PMID- 1354277
TI  - Antibodies to silicone elastomers and reactions to ventriculoperitoneal shunts.
AB  - Silicone elastomers used to make medical implants and prostheses are generally
      believed to be biologically inert. However, we have seen two patients who showed
      severe, apparently immunemediated, reactions to ventriculoperitoneal (VP) shunts.
      We used an enzyme-linked immunosorbent assay in which Silastic tubing served as
      the solid-phase antigen to test serum from the two patients, five other VP shunt
      patients without inflammatory reactions, and nine healthy adults. IgG binding to
      Silastic tubing was consistently higher in the two patients than in the healthy
      or patient controls. The IgG seemed to be binding specifically, since IgG Fab
      fragments also bound to the tubing, and preincubation of serum with Silastic or
      silylated proteins removed most of the activity. These findings show that
      specific immune reactivity to elastomers of polydimethylsiloxane can develop in
      human beings.

PMID- 1354278
TI  - Cardiac resuscitation with percutaneous cardiopulmonary support.
AB  - Percutaneous cardiopulmonary support (CPS) was initiated in 9 patients to provide
      haemodynamic stability after failure of conventional resuscitation. 4 patients
      were in cardiogenic shock and 4 remained in asystole, with 1 in resistant
      ventricular fibrillation, after cardiac arrest. During CPS for those in
      cardiogenic shock, the mean intra-arterial pressures ranged from 65 to 100 mm Hg
      (mean 84), at flow rates of between 3 to 5 l/min (mean 3.9). 2 patients underwent
      technically successful coronary angioplasty. No patient in this group survived.
      In the cardiac arrest group, acceptable mean intra-arterial blood pressures were
      achieved (mean 95, range 90-100 mm Hg) at flow rates of between 2 to 3 l/min
      (mean 2.6). All 5 subjects underwent technically successful coronary angioplasty
      whilst on CPS. 4 survived. 2 were alive and well at 12 months follow-up, 1 of
      whom had returned to work; the third is alive and well at 4 months.

PMID- 1354280
TI  - Cytoreduction in ovarian cancer.

PMID- 1354279
TI  - Bleeding oesophageal varices: IST, EVL, or TIPS.

PMID- 1354281
TI  - Prognostic factors in breast cancer: biology or chronology?

PMID- 1354282
TI  - Traitors to their sex?

PMID- 1354283
TI  - More brevity in The Lancet.

PMID- 1354284
TI  - Should patients with Bjork-Shiley valves undergo prophylactic replacement?
AB  - About 85,000 patients have undergone replacement of diseased heart valves with
      prosthetic Bjork-Shiley convexo-concave (CC) valves. These valves are prone to
      fracture of the outlet strut, which leads to acute valve failure that is usually
      fatal. Should patients with these valves undergo prophylactic replacement to
      avoid fracture? The incidence of strut fracture varies between 0% and 1.5% per
      year, depending on valve opening angle (60 degrees or 70 degrees), diameter (less
      than 29 mm or greater than or equal to 29 mm), and location (aortic or mitral).
      Other factors include the patient's life expectancy and the expected morbidity
      and mortality associated with reoperation. We have used decision analysis to
      identify the patients most likely to benefit from prophylactic reoperation. The
      incidence of outlet strut fracture was estimated from the data of three large
      studies on CC valves, and stratified by opening angle, diameter, and location. A
      Markov decision analysis model was used to estimate life expectancy for patients
      undergoing prophylactic valve replacement and for those not undergoing
      reoperation. Prophylactic valve replacement does not benefit patients with CC
      valves that have low strut fracture risks (60 degrees aortic valves and less than
      29 mm, 60 degrees mitral valves). For most patients with CC valves that have high
      strut fracture risks (greater than or equal to 29 mm, 70 degrees CC),
      prophylactic valve replacement increases life expectancy. However, elderly
      patients with such valves benefit from prophylactic reoperation only if the risk
      of operative mortality is low. Patient age and operative risk are most important
      in recommendations for patients with CC valves that have intermediate strut
      fracture risks (less than 29 mm, 70 degrees valves and greater than or equal to
      29 mm, 60 degrees mitral valves). For all patients and their doctors facing the
      difficult decision on whether to replace CC valves, individual estimates of
      operative mortality risk that take account of both patient-specific and
      institution-specific factors are essential.

PMID- 1354285
TI  - Effect of blood transfusion on survival among children in a Kenyan hospital.
AB  - In Africa, blood transfusions are frequently given to treat severe paediatric
      anaemia. Because of the risk of HIV transmission, identification of when
      transfusion will reduce the risk of death for severely anaemic children has
      become increasingly important. For all children admitted to a Kenyan hospital
      from October, 1989, to October, 1990, we collected data on clinical presentation,
      haemoglobin (Hb), receipt of transfusion, and in-hospital survival. Of 2433
      admissions, 29% (684) had severe anaemia (Hb less than 5.0 g/dl), and 20% (483)
      received blood transfusions. Based on laboratory criteria only, children with Hb
      less than 3.9 g/dl who were transfused had lower mortality than those with Hb
      less than 3.9 g/dl who were not transfused, but this finding applied only to
      children transfused on the day of admission (odds ratio [OR] 0.30; 95% Cl 0.14,
      0.61) or the day after admission (OR 0.37; 95% Cl 0.14, 1.00). Based on a
      combination of laboratory and clinical criteria, children with clinical signs of
      respiratory distress and Hb less than 4.7 g/dl who were transfused had lower
      morality than those who were not (OR 0.19; 95% Cl 0.09, 0.41). Among children
      without respiratory distress, there was no association between receipt of
      transfusion and mortality, irrespective of admission Hb. The frequency of blood
      transfusion can be reduced and survival enhanced by targeting blood to those
      children with severe anaemia and clinical signs of respiratory distress, and by
      using transfusion early in the course of hospitalisation.

PMID- 1354286
TI  - Meta-analysis of intervention trials on case-management of pneumonia in community
      settings.
AB  - To appraise the effectiveness of the pneumonia case-management strategy in
      improving child survival, we have done a meta-analysis of six published
      intervention trials. The results of a seventh published study and two unpublished
      studies were also reviewed. The six published studies satisfied our criteria for
      methodological soundness. The reduction in mortality rate (control group minus
      intervention group) was estimated for each study, and for all the studies
      together. For total infant mortality, the overall reduction was 15.9 (95%
      confidence interval 10.6-21.1) deaths per 1000 livebirths; infant mortality due
      to acute lower respiratory infection was reduced by 10.7 (4.8-16.7) deaths/1000
      livebirths. Mortality among children under 5 years was decreased by 36
      deaths/1000 livebirths. The pooled estimates of relative risk are consistent with
      a 20% reduction in infant mortality and a 25% reduction in under-5 mortality.
      There was no clear association across the studies between the effect of the
      pneumonia case-management and extent of co-interventions such as immunisation and
      oral rehydration therapy. The consistency of findings of all the studies, despite
      differences in design and methods, shows that the case-management strategy has a
      substantial effect on infant and under-5 mortality, at least in settings with
      infant mortality rates of 90/1000 livebirths or more. It is important to find out
      the most efficient ways of implementing this strategy and integrating it into
      primary health care.

PMID- 1354287
TI  - The cardiovascular system of barosaurus: an educated guess.

PMID- 1354288
TI  - Retraction, comment, and errata policies of the US National Library of Medicine.

PMID- 1354289
TI  - HIV transmission and the law.

PMID- 1354290
TI  - Misuse of calcium antagonists after myocardial infarction.

PMID- 1354291
TI  - Known vitamin K intake and management of poorly controlled oral anticoagulant
      therapy.

PMID- 1354292
TI  - Asystole and cardiogenic shock due to combined treatment with verapamil and
      flecainide.

PMID- 1354294
TI  - Potential hazards in estimation of gastric intramucosal pH.

PMID- 1354293
TI  - Alteplase for hepatic veno-occlusive disease after bone marrow transplantation.

PMID- 1354295
TI  - Continuous monitoring of glucose with a transcutaneous microdialysis probe.

PMID- 1354296
TI  - Development of type 1 diabetes mellitus during interferon alfa therapy for
      chronic HCV hepatitis.

PMID- 1354297
TI  - Treatment of hypercholesterolaemia in children.

PMID- 1354298
TI  - L-arginine plasma concentrations in hypercholesterolaemia.

PMID- 1354299
TI  - Non-surgical left ventricular preparation for arterial switch in transposition of
      the great arteries.

PMID- 1354300
TI  - Glove powder introduced in the circulation by autotransfusion and severe cardiac
      failure.

PMID- 1354301
TI  - Larva migrans syndrome: toxocara, ascaris, or both?

PMID- 1354302
TI  - Crossreactions between Legionella and Campylobacter spp.

PMID- 1354303
TI  - Crossreactions between Legionella and Campylobacter spp.

PMID- 1354304
TI  - Cefuroxime resistance in Haemophilus influenzae.

PMID- 1354305
TI  - Cytological surveillance for mild cervical dyskaryosis.

PMID- 1354306
TI  - Cytological surveillance for mild cervical dyskaryosis.

PMID- 1354307
TI  - Health of the nation and sexually transmitted diseases.

PMID- 1354308
TI  - Specialist medical training and the EC.

PMID- 1354309
TI  - Specialist medical training and the EC.

PMID- 1354310
TI  - Philosophy of science.

PMID- 1354311
TI  - "Early intervention" in psychiatric emergencies.

PMID- 1354312
TI  - Prevention of atopic disease in children.

PMID- 1354314
TI  - Naturally occurring "Rochalimaea henselae" infection in domestic cat.

PMID- 1354313
TI  - Traveller's diarrhoea associated with cyanobacterium-like bodies.

PMID- 1354315
TI  - Acute meningoencephalitis associated with seroconversion to "Afipia felis".

PMID- 1354316
TI  - Cities, winter birth, and schizophrenia.

PMID- 1354317
TI  - Antibodies to HIV-1 in urine of children of HIV-1-infected women.

PMID- 1354318
TI  - Cities, winter birth, and schizophrenia.

PMID- 1354320
TI  - Serological evidence for culture-negative listeriosis of central nervous system.

PMID- 1354319
TI  - Ganciclovir/foscarnet for cytomegalovirus meningoencephalitis in AIDS.

PMID- 1354321
TI  - Requisite structural characteristics for benzodiazepine inhibition of
      triiodothyronine uptake into a human liver cell line.
AB  - Previously, we reported potent inhibition of triiodo-L-thyronine (T3) cellular
      uptake into a human liver cell line (HepG2) by central and peripheral receptor
      specific benzodiazepine (BZ) compounds and our working hypothesis of BZ's as
      direct competitors for the iodothyronine transporter, displacing T3 but not
      acting as a substrate for transport. In this report, we list other reported
      uptake inhibitors and compare them to 23 benzodiazepine receptor ligands, in
      their potency to inhibit cellular uptake of T3. The most potent inhibitors are
      restricted to the benzodiazepine class. From the BZ structure-activity
      relationship (SAR) for inhibition, we see that the nonfused phenyl ring may be
      essential for activity and the strongest relationship is seen with substitution
      at R2' where Cl greater than F greater than H. Substitution at R4' and hydroxyl
      substitution at R3 enhances potency as will alkyl groups at R1 or on the
      imidazole group in the 1,2-annelated series. With R7 substitution, Cl is
      preferred over NO2 but not necessarily H when R4' = Cl; this may reflect a
      slightly different orientation of the molecule with large aliphatic R1 groups
      and/or R4' substitution. The carbonyl at R2 in the 1,4 benzodiazepine series,
      enhances their potency. The resultant structure-activity relationship highlights
      the importance of the halogen-substituted nonfused phenyl ring and seems unique
      relative to other described benzodiazepine sites and/or effects.

PMID- 1354322
TI  - Adrenoceptor mechanisms in the cardiovascular effects of cocaine in conscious
      squirrel monkeys.
AB  - The purpose of the current experiment was to study the role of various
      adrenoceptor subtypes in the cardiovascular response to cocaine in conscious
      squirrel monkeys. A variety of adrenoceptor antagonists were administered i.v.
      prior to the administration of 0.3 mg/kg cocaine (i.v.). Cocaine alone produced
      an increase in both blood pressure and heart rate. The non-selective alpha
      adrenoceptor antagonist phentolamine produced a dose-dependent antagonism of the
      pressor effect of cocaine, as did the alpha-1 selective antagonist prazosin. The
      alpha-2 selective antagonist yohimbine had no effect on the pressor effect of
      cocaine. The non-selective beta antagonist propranolol enhanced the pressor
      effect of cocaine as did the beta-1 selective antagonist atenolol. However, the
      effect of atenolol was not dose-dependent. The beta-2 selective antagonist ICI
      118,551 and labetalol, which blocks both alpha and beta adrenoceptors, did not
      alter the pressor effect of cocaine. Propranolol, atenolol, and labetalol all
      antagonized the tachycardiac effect of cocaine in a dose-dependent manner, while
      the beta-2 antagonist ICI 118,551 did not. Phentolamine, prazosin and yohimbine
      also reduced the tachycardiac effect of cocaine, although these effects were dose
      dependent only for yohimbine, which also significantly elevated baseline heart
      rate. These results indicate that alpha-1 adrenoceptor mechanisms mediate the
      pressor effect of cocaine, while beta-1 adrenoceptor mechanisms are involved in
      the tachycardiac effect of cocaine in squirrel monkeys. Propranolol potentiated
      cocaine's pressor effect through beta-2 independent mechanisms. Thus, neither
      alpha-2 nor beta-2 adrenoceptor mechanisms appear to be involved in cocaine's
      cardiovascular effects.

PMID- 1354323
TI  - Short echo time proton spectroscopy of human brain using a gradient head coil.
AB  - Short echo time, single voxel localized proton spectroscopy was accomplished
      using a stimulated echo (STEAM) sequence running on a Siemens 1.5-T system with a
      head coil incorporating the Z and Y gradients. Spectra from the temporal lobe,
      the cerebellum and mid brain were acquired from a group of normal volunteers
      using the following parameters: voxel size = 8 ml, TE = 22 msec, 512 signal
      averages and TR = 1.7 sec. STEAM spectra acquired with the small diameter
      gradients showed significantly fewer artifacts at short TE, allowing the
      observation of glutamate/glutamine, GABA, taurine, and inositol in addition to
      the prominent resonance of choline, creatine/phosphocreatine and N
      acetylaspartate (NAA). The levels of chlorine, creatine and NAA were found to be
      significantly different in the three regions of the brain examined.

PMID- 1354324
TI  - Age and serotype dependent binding of K88 fimbriae to porcine intestinal
      receptors.
AB  - The porcine small intestine contains several polypeptides that could function as
      receptors for K88-positive Escherichia coli. The mucus fraction contained three
      proteins with molecular weights of 25, 35 and 60 kDa respectively, which showed a
      high affinity for K88-positive E. coli cells, whereas brush borders contained a
      16 kDa protein and a set of proteins ranging from 40-70 kDa. Depending on the K88
      serotype tested, differences in binding to these proteins were observed. In
      particular, E. coli cells carrying K88ad fimbriae exhibited only a rather weak
      binding to mucus proteins. The influence of age of the pig on the presence of K88
      receptors was also investigated. One-week-old and 35-days-old post-weaning
      piglets were shown to contain K88 receptors in their mucus while these receptors
      were hardly detectable in the mucus of 6-month-old pigs. The presence of
      receptors in the brush border fraction was shown to be independent of age. The
      binding of K88 fimbriae to mucus proteins was blocked using a lectin of Euonymus
      europeaus which specifically recognizes the Gal alpha(1-3)Gal sequence,
      indicating that this disaccharide forms a significant part of the receptor
      structure.

PMID- 1354325
TI  - GM-CSF production by CD4+ T-lymphocytes is selectively impaired during the course
      of HIV-1 infection. A possible indication of a preferential lesion of a specific
      subset of peripheral blood CD4+ T-lymphocytes.
AB  - The production of granulocyte/macrophage-colony stimulating factor (GM-CSF),
      interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) were
      evaluated in the supernatants of short-term cultures of purified CD4+ T
      lymphocytes and enriched monocytes obtained from peripheral blood (PB) of 35 HIV
      1 seropositive (+) asymptomatic individuals, stages I-II of the Walter Reed (WR)
      classification, 15 HIV (+) symptomatic patients (WR V-VI) and 40 HIV-1
      seronegative normal blood donors. IL-1 beta and TNF-alpha production by either
      enriched monocytes or isolated CD4+ T-cells, was similar in HIV-1 (+)
      asymptomatic, symptomatic subjects and normal controls. GM-CSF level in enriched
      monocyte culture supernatants did not show any significant difference in the
      three groups of subjects under investigation. On the other hand, GM-CSF
      production by isolated CD4+ T-lymphocytes was two-fold decreased in HIV-1 (+)
      asymptomatic subjects and five-fold decreased in HIV-1 (+) symptomatic patients
      with respect to normal blood donors. The decline in GM-CSF production was clearly
      correlated with viral isolation from patient's PB light density mononuclear cells
      (r = -0.920, p less than 0.01). The selective and progressive decline in GM-CSF
      production by CD4+ T-lymphocytes, starting from early stages of HIV-1 infection,
      suggest a preferential lesion of a specific subset of CD4+ T-lymphocytes
      characterized by an intense production of GM-CSF and may contribute to explain
      the deranged inflammatory and immune responses which characterize the course of
      HIV-1 infection.

PMID- 1354326
TI  - Application of immunohistochemical techniques to sural nerve biopsies.
AB  - The role of immunohistochemistry in the day-to-day diagnostic work of a
      peripheral nerve laboratory is not yet clearly established, although for
      conditions such as amyloid neuropathy, immunohistochemistry appears to be a
      useful adjunct to conventional techniques. Immunohistochemistry has provided new
      information about some neuropathies in which immune dysfunction is believed to
      play a central role. Immunohistochemical data about normal human nerve are
      scarce; a better appreciation of the normal cellular constituents of nerve,
      particularly the endoneurium, is needed. In the future, the techniques may be a
      means to understand better the pathogenesis of other types of neuropathy, such as
      inherited or toxic neuropathies, or to examine fundamental pathologic events such
      as axonal degeneration.

PMID- 1354327
TI  - Availability of flow cytometric immunophenotyping of lymphocytes to hospital
      patients--United States, 1990.
AB  - The pathogenesis of disease caused by human immunodeficiency virus (HIV) is
      largely attributable to the decrease in T-lymphocytes bearing the CD4 cell
      surface molecule (CD4 + T-lymphocytes) (1). The percentage of CD4 + T-lymphocytes
      among total lymphocytes and the percentages of other lymphocyte subpopulations
      (e.g., CD8 + T-lymphocytes) are generally measured by flow cytometric
      immunophenotyping (FCl) (also called immunophenotyping by flow cytometry [2], T
      lymphocyte immunophenotyping [3], and fluorescence-activated cell sorting). FCl
      results are frequently used to guide the treatment of HIV-infected persons. To
      assess the availability of FCl to hospital patients, in 1990, the National Public
      Health and Hospital Institute (NPHHI), a private, nonprofit research institute,
      surveyed hospitals about their provision of FCl to patients. This report presents
      findings from the survey.

PMID- 1354328
TI  - Identification of a novel transglutaminase from the filarial parasite Brugia
      malayi and its role in growth and development.
AB  - Recently, we reported the presence of a putative transglutaminase in adult female
      worms of Brugia malayi [1]. The enzyme activity was shown to be essential for in
      utero growth and development of microfilariae. Here, we demonstrate that adult
      worms of B. malayi have a large amount of epsilon-(gamma-glutamyl)lysine
      isopeptide bonds, a product of physiologically active transglutaminase. A 25-kDa
      immunoreactive band detected in female worm extracts by a monospecific monoclonal
      antibody (CUB 7401) against guinea pig liver transglutaminase was associated with
      the enzymatic activity. Unlike the mammalian enzyme, the parasite enzyme did not
      require Ca2+ for its catalytic activity. Furthermore, in utero developing
      embryos, especially during early stages of development, contained very high
      amounts of this enzyme. Adult female worms contained several proteins that could
      serve as suitable substrates for the enzyme. Inhibition of the enzyme activity by
      an enzyme-specific pseudosubstrate, monodansylcadaverine, led to a time- and dose
      dependent inhibition of microfilariae production and release by gravid female
      worms. The inhibition of microfilariae production was due to the inhibition of
      transglutaminase-catalyzed crosslinking of parasite proteins that in turn seemed
      to be essential for in utero growth and development of the embryos. The results
      suggest that transglutaminase-catalyzed reactions may play an important role
      during early development of embryos to mature microfilariae inside the adult
      female worms of filarial parasites.

PMID- 1354329
TI  - [The effect of 2,4-dichlorophenol on enzyme activities and other parameters in
      parenchymatous organs of rats].
AB  - After repeated administration of 2,4-dichlorophenol the aminopeptidases AAP and
      LAP, and the alkaline phosphatase in various organs were influenced. The
      treatment causes stimulatory or inhibitory activities. Also with histological and
      histochemical methods damages could be detected.

PMID- 1354330
TI  - Hydra and the homeobox.

PMID- 1354331
TI  - [New aspects in the diagnosis, pathogenesis and therapy of schizophrenic negative
      symptoms].
AB  - The treatment of negative symptoms requires a thorough diagnostic assessment.
      Their lack of homogeneity has important clinical implications. Negative symptoms
      are unspecific for schizophrenia, differ in cause and manifestation, and may
      appear at all stages of the illness. There is much evidence for the responsivity
      of negative symptoms to pharmacological and psychosocial treatment. This paper
      gives a short survey of the historical development of the concept of negative
      symptoms, the development of scales specifically measuring both negative and
      positive symptoms, and various recently discussed hypotheses concerning
      pathogenesis and treatment strategies. Important is a therapeutic concept
      individually adjusted to the patient's needs, including pharmacological,
      psychotherapeutic and social measures.

PMID- 1354332
TI  - [Pisa syndrome].
AB  - The Pisa Syndrome is a rare dystonic syndrome, first described by Ekbom et al.
      1972 as a side effect of neuroleptic therapy and subsequently by Patel et al.
      1991 as a symptom of dementia of the Alzheimer type. It consists of tonic flexion
      of the trunk to one side, accompanied by a slight rotation. The presentation of
      three clinical cases, including one without neuroleptic but with thymoleptic
      medication, is followed by etiological and therapeutical considerations as well
      as data concerning the prevalence of this rare syndrome. Finally, the question of
      a possible psychogenesis of this condition is discussed.

PMID- 1354333
TI  - [Adult form of metachromatic leukodystrophy with predominantly psychotic
      manifestations].
AB  - This is a report of one of the few cases of an adult form of metachromatic
      leukodystrophy with almost exclusively psychiatric symptoms. This should point
      out the importance of a careful organic diagnostic assessment in all patients
      with the first manifestation of a psychiatric disease. In this case an
      investigation of the patient's family confirmed the heterozygote genetic origin
      of the disease.

PMID- 1354334
TI  - GABAergic influences on somatostatin secretion from hypothalamic neurons cultured
      in defined medium.
AB  - The effects of GABAergic influences intrinsic to the hypothalamus on the
      secretion of somatostatin were studied using cultured fetal rat hypothalamic
      neurons. The existence of GABAergic neurons within the cultures was confirmed by
      immunocytochemistry. These neurons appeared to be actively secreting GABA as
      antagonism of GABAA receptors with bicuculline and picrotoxinin caused a dose
      dependent increase in the release of immunoreactive somatostatin (SRIF), which
      was Ca(2+)-dependent. Although exogenous GABA inhibited SRIF secretion at
      concentrations of 10(-6) M and greater, muscimol, a GABAA agonist, inhibited SRIF
      release at 10(-8) M, whereas baclofen, a GABAB agonist, required concentrations
      two orders of magnitude greater to produce an effect. Phaclofen, a GABAB
      antagonist, was inactive (10(-8)-10(-4) M). A GABA uptake inhibitor, SKF 89976A,
      produced a dose-dependent inhibition of SRIF release. These results, therefore,
      support a role for intrahypothalamic GABA neurons in the regulation of SRIF
      secretion in the neonatal rat, predominantly via a type A receptor, and provide
      further evidence for a neuroendocrine role for GABA in controlling growth hormone
      secretion.

PMID- 1354335
TI  - Dopaminergic regulation of luteinizing hormone-releasing hormone release at the
      median eminence level: immunocytochemical and physiological evidence in hens.
AB  - Theoretically, the most effective inhibitory control of hypophysiotropic
      luteinizing hormone-releasing hormone (LHRH) release might occur through a
      presynaptic inhibition of LHRH neuronal terminals at the median eminence (ME)
      level. Since: (a) we have recently reported the existence of synaptic contacts
      between dopamine- and LHRH-containing processes in the ewe ME, and (b)
      nutritional deprivation induces an ovulatory failure in both birds and mammals,
      we have assessed the possibility that the anovulatory state induced by feed
      withdrawal (FW) in laying hens, might be caused by a dopaminergic inhibition of
      LHRH release at the ME level. Laying hens at the start (35 weeks old) and end (75
      weeks old) of their commercial egg-laying life were killed at 0, 1, 2 and 4 days
      after FW. Serum luteinizing hormone (LH) and progesterone (P4), in vitro release
      of LHRH by isolated ME, and LHRH content in ME and preoptic area (POA) were
      determined by RIA. ME content of dopamine (DA) and its main metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC) were assessed by LCED. The distribution of
      LHRH and tyrosine hydroxylase (TH)-containing processes at the ME level of the
      hen was determined immunocytochemically. In the hen, LHRH-containing cell bodies
      are localized in the anterior hypothalamus and medial POA. LHRH-containing axons
      project toward the ME and infundibulum through the ventral-lateral hypothalamus.
      TH-containing perikarya are concentrated in the arcuate nucleus and in the
      adjacent part of the periventricular nucleus, dorsal to the arcuate. TH
      containing axons converge toward the ME and descend into the infundibulum. Dense
      concentrations of TH- and LHRH-containing processes are located in the lateral
      and mediobasal portions of the external layer of the ME, providing opportunities
      for synaptic interactions between them. Ovulatory failure and regression of the
      ovary and reproductive tract occurred 2-3 days after FW at the end, but not at
      the beginning of the hen's commercial egg-laying life. After FW, hens at the end
      of their productive life had higher (p less than 0.01) tuberoinfundibular DA
      turnover, produced less LHRH, and had lower serum LH and P4 than hens undergoing
      FW at the beginning of their productive life. In addition, in vitro release of
      HRH from denervated ME tissue of hens undergoing FW at the end of their
      commercial egg-laying life was higher and was reversed in a dose-dependent
      fashion by DA, but not by serotonin. Thus, the ovulatory failure associated with
      FW in laying hens might be caused by a presynaptic inhibition of in vivo LHRH
      release at the level of ME hypothalamic neuronal terminals.

PMID- 1354336
TI  - Dynorphin-processing endopeptidase in the rat anterior pituitary lactotrophic
      cell line, GH4C1.
AB  - Several peptide hormones and neurotransmitters are produced by cleavage at the
      monobasic processing sites. An endoprotease capable of cleaving a dynorphin
      peptide at the monobasic processing site is secreted from the rat anterior
      pituitary lactotrophic cell line, GH4C1. When characterized by fast protein
      liquid chromatography using an ion exchange column, the majority of the
      endoprotease activity elutes as a single symmetrical peak around 0.3 M NaCl. The
      protease inhibitor profile suggests that the activity is due to putative thiol
      protease. These enzymatic properties are similar to a monobasic processing enzyme
      previously found in bovine pituitary and in the rat brain. The secretory pathway
      which contains the enzyme activity in GH4C1 cells was characterized by
      stimulation of secretion by thyrotropin releasing hormone, forskolin, phorbol
      ester, or potassium chloride. The secretion of the enzyme activity was
      substantially increased by these compounds suggesting that the GH4C1 cells
      secrete the activity via the regulated pathway. A hormonal treatment of the GH4C1
      cells which has been previously shown to produce a substantial increase in the
      number of secretory granules and ir-prolactin has been found in this study to
      elevate this enzyme activity 2-fold. This increase is similar to that seen in the
      carboxypeptidase E activity, another putative peptide hormone processing enzyme
      activity. These data suggest that the peptide processing activity is regulated to
      a small but significant extent and is coordinately regulated with
      carboxypeptidase E activity.

PMID- 1354337
TI  - Release of endogenous amino acids, including homocysteic acid and cysteine
      sulphinic acid, from rat hippocampal slices evoked by electrical stimulation of
      Schaffer collateral-commissural fibres.
AB  - This study examined the release of endogenous amino acids from acute hippocampal
      slices, upon stimulation of the Schaffer collateral-commissural fibres. One
      minute samples of superfusate were collected via a cannula placed over the CA1
      stratum radiatum, and were analysed by reversed-phase high performance liquid
      chromatography. Evoked potentials were recorded to ascertain stimulation
      efficacy. Four minutes of continuous 50 Hz stimulation produced a tetrodotoxin
      sensitive release of aspartate and glycine in the second minute of stimulation,
      as well as a tetrodotoxin-sensitive release of cysteine sulphinic acid, during
      stimulation and of homocysteic acid, following stimulation. Such 50 Hz
      stimulation also produced a tetrodotoxin-insensitive decrease in methionine
      levels, but no significant changes in any of the other 15 amino acids measured.
      Four minutes of continuous 1 Hz stimulation produced no changes in the levels of
      any of the amino acids measured, but four 600-ms trains of 100 Hz stimulation,
      which, unlike the 1 Hz stimulation, produced long-term potentiation, resulted in
      significant increases in levels of cysteine sulphinic acid and homocysteic acid,
      but not of any of the other amino acids measured. These results suggest that
      aspartate, glycine, homocysteic acid, and cysteine sulphinic acid play a role in
      synaptic transmission in the Schaffer collateral-commissural fibres, and that
      cysteine sulphinic acid and homocysteic acid may be released specifically by high
      frequency stimulation.

PMID- 1354338
TI  - Comparison of neuronal inositol 1,4,5-trisphosphate 3-kinase and receptor mRNA
      distributions in the adult rat brain using in situ hybridization histochemistry.
AB  - As a result of its interaction with a specific receptor, inositol 1,4,5
      trisphosphate mobilizes intracellular calcium. The metabolism of inositol 1,4,5
      trisphosphate is rather complex: inositol 1,4,5-trisphosphate 3-kinase produces
      inositol 1,3,4,5-tetrakisphosphate, a putative second messenger. In order to
      elucidate inositol 1,3,4,5-tetrakisphosphate function, a comparative in situ
      hybridization study of the distributions of inositol 1,4,5-trisphosphate 3-kinase
      and receptor mRNAs was performed in the adult rat brain using oligonucleotides
      derived from their cDNA sequences. The neuronal distributions of the mRNA for the
      receptor were larger than for the kinase. Highest levels of both mRNAs were found
      in the cerebellar Purkinje cells, where they were enriched in their neuronal
      perikarya and to a lesser extent in their dendrites. In addition to the
      cerebellum, mRNAs were mainly detected in the hippocampal pyramidal cells of the
      CA1 sector of the Ammon's horn and in the granule cells of the dentate gyrus, and
      also in a majority of the neurons in the cortical layers II-III and V, especially
      in the frontal cortex and cingulate cortex; caudate-putamen, accumbens, olfactory
      tubercle and Calleja islets; claustrum; anterior olfactory nucleus; taenia tecta;
      piriform cortex; dorsolateral septum; bed nucleus stria terminalis; amygdala;
      hippocampal CA2-4 sectors and subiculum. The inositol 1,4,5-trisphosphate
      receptor mRNA but not kinase mRNA was found in a majority of the neurons in the
      thalamus, especially in the parafascicular nucleus; hypothalamus, especially the
      medial hypothalamus; substantia nigra pars compacta and ventral tegmental area;
      superior colliculus; lateral interpeduncular nucleus and central gray. Taking
      into account the limitation in sensitivity of the technique, both mRNAs were not
      detected in glial cells and in the olfactory bulb; basal nucleus of Meynert,
      diagonal band nuclei; medial septal nucleus; substantia innominata; globus
      pallidus; entopeduncular nucleus; substantia nigra pars reticulata; ventral
      pallidum; subthalamic nucleus; spinal cord and dorsal root ganglia. In
      conclusion, cerebellum and hippocampus appear to contain almost similar levels of
      kinase mRNA. This is in contrast to receptor mRNA levels which were at much
      higher levels in the cerebellum when compared with the hippocampus. For this
      reason, we have chosen hippocampal CA1 pyramidal cells and dentate gyrus granule
      cells for studying inositol 1,4,5-trisphosphate 3-kinase function.

PMID- 1354339
TI  - Neurotensin increases tyrosine hydroxylase messenger RNA-positive neurons in
      substantia nigra after retrograde axonal transport.
AB  - In previous studies we have shown that labelled neurotensin injected into the rat
      striatum was found to be transported retrogradely in dopaminergic neurons through
      a process which was receptor and microtubule dependent. Now, we show, by in situ
      hybridization, the consequences of the striatal injection of neurotensin on the
      gene expression of tyrosine hydroxylase in the substantia nigra. Rats were
      injected with neurotensin or its fragments in the striatum of one side and with
      saline or the inactive fragment on the other. The number of nigral cells
      expressing tyrosine hydroxylase mRNA was found to increase by 40% after injection
      of neurotensin or its active fragment (neurotensin 8-13). In the same
      experimental conditions, the inactive fragment (neurotensin 1-8) was without
      effect. Time-course experiments revealed that the tyrosine hydroxylase mRNA was
      increased 4 h after neurotensin injection but not at 1 or 16 h. The fact that the
      increase of mRNA parallels the appearance of labelled neurotensin in the
      substantia nigra indicates that the changes in the gene expression of tyrosine
      hydroxylase might be the consequence of the retrograde axonal transport of
      neurotensin. These results represent the first evidence for the existence of a
      long-distance retrograde signalling process in which the neuropeptide and
      presumably its receptor may serve as information molecule between synapses and
      the cell body.

PMID- 1354340
TI  - Physiological effects of chronic and acute application of N-methyl-D-aspartate
      and 5-amino-phosphonovaleric acid to the optic tectum of Rana pipiens frogs.
AB  - Visually elicited activity contributes to the formation of orderly connections in
      the optic tectum of frogs. Glutamate receptors of the N-methyl-D-aspartate class
      participate in this process. Blocking those receptors interferes with activity
      dependent refinement of maps in normal frogs and of ocular dominance bands in
      surgically produced animals with three eyes. Chronic application of N-methyl-D
      aspartate sharpens the bands. The possibility that 5-amino-phosphonovaleric acid
      depresses tectal responsiveness was motivation for studying the effects of 5
      amino-phosphonovaleric acid and N-methyl-D-aspartate applied both chronically and
      acutely. We evaluated tectal responsiveness to visual input by presenting flashes
      of light to one eye and recording responses in the ipsilateral tectal lobe. This
      method reveals the output of the tectal cells contralateral to the stimulated
      eye. These cells project via the nucleus isthmi to the opposite tectal lobe. We
      also mapped the receptive field dimensions of the crossed isthmotectal axons. Our
      results show that acute topical application of 500 microM or 1 mM N-methyl-D
      aspartate dramatically increases spontaneous activity, while 100 microM N-methyl
      D-aspartate causes little change. Chronic treatment with N-methyl-D-aspartate at
      a low dose (estimated to be in the micromolar range) shown to influence
      retinotectal mapping, reduces response latencies but produces no statistically
      significant changes in tectal cell firing rates or receptive field size. Acute
      application of 5-amino-phosphonovaleric acid produces complex results: 10 microM
      produces no changes in firing, 100 microM 5-amino-phosphonovaleric acid decreases
      firing, and doses of 500-100 microM increase the firing.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1354341
TI  - Peroxide effects on [3H]L-glutamate release by synaptosomes isolated from the
      cerebral cortex.
AB  - Basal (non-depolarized) and high K(+)-stimulated [3H]L-glutamate release in the
      presence and absence of Ca2+ were assessed using presynaptic nerve terminals
      (synaptosomes) isolated from the cerebral cortex of the guinea pig. Basal
      glutamate release was found to be Ca(2+)-independent and was significantly
      increased following treatment with hydrogen peroxide (H2O2). On the other hand,
      depolarization-induced release had both a Ca(2+)-dependent and Ca(2+)-independent
      component. Both components of stimulated release were suppressed by H2O2. In
      fact, Ca(2+)-dependent evoked release was virtually eliminated by H2O2
      pretreatment. The data suggest that H2O2 exerts a differential effect on the
      neurochemical mechanisms involved in basal and stimulated glutamate release at
      the presynaptic nerve terminal.

PMID- 1354342
TI  - Tau antigenic changes induced by glutamate in rat primary culture model: a
      biochemical approach.
AB  - Primary neuronal cultures were treated with glutamate to induce an increase of
      Tau immunoreactivity similar to that observed in Alzheimer's disease. The Tau
      profile of neurones in culture before and after exposure to glutamate was
      analyzed on immunoblots with anti-Tau, anti-paired helical filaments (PHF) and
      antibody specific for modified Tau. Differences were observed between treated and
      control cultures: glutamate induced a shift of immunodetection from the lowest to
      the highest molecular weight Tau isoform and an acidification of Tau proteins.
      However, these modifications are not exactly those observed in Alzheimer's
      disease since we were not able to detect 'Alzheimer-type' epitopes on Tau
      proteins after the glutamate exposure.

PMID- 1354343
TI  - Pertussis toxin pretreatment abolishes the inhibitory effect of riluzole and
      carbachol on D-[3H]aspartate release from cultured cerebellar granule cells.
AB  - The release of D-[3H]aspartate from cultured cerebellar granule cells evoked by
      glutamic acid can be inhibited by riluzole and the muscarinic agonist carbachol.
      The combined application of maximally efficacious concentrations of riluzole and
      carbachol produces no greater inhibition than that seen with either agent alone,
      indicating that a common mechanism is involved. The effects of both agents are
      abolished when the cells have been pretreated with pertussis toxin, which
      suggests that this mechanism may involve a GTP-binding protein. The effect of
      pertussis toxin pretreatment is not mimicked by cholera toxin, nor does pertussis
      toxin pretreatment interfere with the inhibitory effect of the competitive
      excitatory amino acid receptor antagonist D-alpha-aminoadipic acid.

PMID- 1354345
TI  - [Student meeting in Lower Austria].

PMID- 1354344
TI  - Clinical experiences with platinum and etoposide therapy in lung cancer.

PMID- 1354346
TI  - Characterization of a paired box- and homeobox-containing quail gene (Pax-QNR)
      expressed in the neuroretina.
AB  - The retina is an integral part of the central nervous system, and consists of two
      layers, the outer pigmented layer and the inner sensory layer or neuroretina
      (NR). The NR layer contains several strata of cells (glial and neuronal) derived
      from proliferating neuroectodermal precursors that differentiate after terminal
      mitosis. In vitro, NR cells can differentiate not only into neuronal and glial
      types, but also into pigment and lens cells. Quail (Coturnix coturnix japonica)
      NR cells (QNR) infected with MC29 transforming retrovirus become pigmented after
      several passages in vitro. In order to characterize the genes expressed in these
      pigmented MC29 QNR, a cDNA library was prepared from these cells. After
      differential screening we have isolated a cDNA clone which identifies an RNA
      expressed in NR but not in the pigmented layer of the retina. This cDNA encodes a
      protein related to that of Drosophila, mouse and zebrafish paired box- and
      homeobox-containing segmentation genes and is called Pax-QNR. The expression of
      Pax-QNR in the NR is confined to the ganglionic cell layer and to the lower part
      of the inner nuclear layer containing the amacrine or correlation neurones.

PMID- 1354347
TI  - Transient expression of the Epstein-Barr virus LMP1 gene in human primary B cells
      induces cellular activation and DNA synthesis.
AB  - The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) and Epstein
      Barr virus nuclear antigen 2 (EBNA2) are expressed in EBV-immortalized human B
      cells. It has previously been shown that transfection of the LMP1 and EBNA2 genes
      into Burkitt's lymphoma cell lines results in the up-regulation of CD23, CD21,
      ICAM-1 and LFA-1 cell-surface proteins. In the present study, the effects of
      transient expression of the LMP1 and EBNA2 genes were studied in normal primary
      human B cells pretreated with UV-inactivated EBV particles. To identify and
      purify cells which express the transfected DNA we used a gene encoding a surface
      molecule, CD2, as a co-transfection marker. We show that transient expression of
      the LMP1 gene, from heterologous promoters, is sufficient to induce cellular
      enlargement and up-regulation of surface expression of the activation markers
      CD23, CD21, ICAM-1 and LFA-1 in primary B cells. Most importantly, we show that
      transient expression of the LMP1 gene is sufficient to induce DNA synthesis in
      human primary B cells. Transient EBNA2 expression enhanced the effect of
      transient LMP1 expression on CD21 and CD23 cell-surface expression but, under our
      experimental conditions, inhibited the induction of DNA synthesis by LMP1. We
      conclude that activation of primary B cells with inactivated EBV particles,
      followed by transient expression of only two viral genes, EBNA2 and LMP1, is
      sufficient to reconstitute some of the early events of B-cell immortalization by
      EBV.

PMID- 1354348
TI  - Transformation mediated by the human HER-2 gene independent of the epidermal
      growth factor receptor.
AB  - Amplification of the HER-2 (c-erbB-2) gene and overexpression of the p185HER-2
      gene product is found in approximately one-third of primary human breast and
      ovarian cancers and is associated with a poor clinical outcome of early relapse
      and death. The HER-2 gene encodes a cell-surface growth factor receptor with
      intrinsic tyrosine kinase activity. Wild-type human HER-2 has been shown to act
      as a potent oncogene when over-expressed in mouse fibroblasts. Recent data
      suggest that the mechanism by which HER-2 mediates transformation requires the
      interaction of the epidermal growth factor (EGF) receptor. To test whether
      overexpression of normal human HER-2 can transform cells independently of the EGF
      receptor, we have introduced multiple copies of HER-2 into the EGF receptor
      negative cell line, NR6, and have performed assays for both transformation and
      tumorigenicity. Engineered NR6 cells that overexpress the HER-2 gene product
      display a highly transformed and tumorigenic phenotype as compared with control
      cells. Additionally, a monoclonal antibody to the extracellular domain of the HER
      2 receptor is able to inhibit the proliferation of the overexpressing cells in
      vitro as well as tumor growth in vivo. This study provides clear evidence that
      HER-2-mediated transformation can be achieved independently of the EGF receptor.

PMID- 1354350
TI  - Recent developments on valproate and its metabolites. Proceedings of a workshop.
      Nijmegen, The Netherlands, 25 January 1991.

PMID- 1354349
TI  - Pharmacological, toxicological and neurochemical effects of delta 2(E)-valproate
      in animals.

PMID- 1354351
TI  - Quality in Pharmacotherapy. 21st European Symposium on Clinical Pharmacy.
      Copenhagen, Denmark, 14-17 October 1992. Abstracts.

PMID- 1354352
TI  - Incomplete stroma formation after allogeneic marrow or autologous blood stem cell
      transplantation.
AB  - Long term and semi-solid culture techniques were used to evaluate the quality of
      stroma produced by bone marrow from 33 normal subjects and 57 patients (46
      allogeneic bone marrow and 11 autologous blood stem cell transplant recipients).
      Bone marrow from transplant recipients was capable of sustained CFU-GM and
      nucleated cell production in long term culture. However, only 13% of the marrow
      investigated developed a complete, confluent stromal layer. These stromal
      abnormalities were observed in spite of complete hematopoietic reconstitution
      after transplantation and rarely improved with time. Our results suggest that the
      hematopoietic microenvironment is very fragile and susceptible to long term
      damage as a result of chemotherapy and the conditioning regimes used prior to
      transplantation.

PMID- 1354353
TI  - Proceedings of the XXVI National Congress of the Italian Society of Pharmacology.
      Naples, Italy, September 29-October 3, 1992. Abstracts.

PMID- 1354354
TI  - Prolactin release from perifused human decidual explants; effects of decidual
      prolactin-releasing factor (PRL-RF) and prolactin release-inhibitory factor (PRL
      IF).
AB  - The dynamics of prolactin release from human decidual explants were studied under
      basal conditions, in response to decidual prolactin-releasing factor (PRL-RF),
      and in response to PRL-RF in the presence of decidual prolactin release
      inhibitory factor (PRL-IF) or other factors known to inhibit prolactin release in
      static cultures. Explants were perifused with medium at a rate of 6 ml/h, and the
      medium was collected at 5 min intervals. The explants released prolactin for up
      to 20 h without evidence of cell necrosis, with the rate of prolactin decreasing
      gradually from 3.9 +/- 0.1 ng/5 min during the first 2 h to 2.2 +/- 0.1 ng/5 min
      during the last 2 h of exposure. PRL-RF, a 23.5 KMr protein released by the
      placenta, stimulated a dose-dependent increase in prolactin release from the
      perifused explants that occurred within the first 5 min of exposure and persisted
      until the exposure to the releasing factor was discontinued. PRL-IF, a 35-45 K Mr
      protein released by the decidua, caused a dose-dependent inhibition of PRL-RF
      mediated prolactin release. Dibutyryl cAMP, cholera toxin, sn-1, 2
      dioctonylglycerol, PMA, and arachidonic acid, which inhibit basal prolactin
      release from static decidual cultures, also caused a dose-dependent inhibition of
      prolactin release in response to PRL-RF. In each instance, the maximal dose of
      the agents tested inhibited PRL-RF-mediated prolactin release by greater than 84
      per cent. These results indicate that the stimulation of prolactin by PRL-RF is
      inhibited by PRL-IF and pharmacologic agents that inhibit basal prolactin
      release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354355
TI  - Carboxyl-terminal deletion and point mutations decrease the transforming
      potential of the activated rat neu oncogene product.
AB  - The rat neu oncogene encodes a constitutively activated growth factor
      receptor/transmembrane tyrosine kinase, p185Tneu, that is structurally similar to
      yet distinct from the epidermal growth factor receptor. To explore the role of
      the carboxyl-terminal region and of putative autophosphorylation sites in
      regulating the activity of the rat p185Tneu (T, transforming) protein, we used
      site-directed mutagenesis to generate a p185Tneu mutant in which a putative
      tyrosine autophosphorylation site (residue 1253) at the extreme carboxyl terminus
      was replaced by a phenylalanine residue and a mutant in which the carboxyl
      terminal 122 amino acids were deleted. These proteins were expressed in NIH 3T3
      cells at comparable levels and exhibited similar autophosphorylation activity,
      exogenous substrate phosphorylation ability, oligomerization levels, and
      responsiveness to a partially purified neu-activating factor. However, the mutant
      p185Tneu proteins displayed a decreased transforming capacity both in vitro and
      in vivo. This analysis demonstrated that the carboxyl-terminal domain and at
      least one putative tyrosine autophosphorylation site of p185Tneu play a role in
      positively regulating the cell growth-regulating properties of the neu protein.

PMID- 1354356
TI  - Segmental determination in Drosophila conferred by hunchback (hb), a repressor of
      the homeotic gene Ultrabithorax (Ubx).
AB  - The activity of homeotic genes in Drosophila cells determines segment-specific
      morphogenesis. Here, we provide evidence that the product of hunchback (hb), a
      segmentation gene, acts as a direct repressor or "silencer" of the homeotic gene
      Ultrabithorax (Ubx) and thus prevents ectopic activity of this gene: we show, by
      stable integration of reporter gene constructs, that hb protein binding sites are
      capable of repressing at a distance the activity of an embryonic Ubx enhancer
      outside the Ubx expression domain. This silencing activity is observed at
      advanced embryonic stages, at a time when the hb gene product is no longer
      detectable or required, and is dependent on the function of Polycomb (Pc). We
      propose a working hypothesis as to how hb protein in a "hit-and-run" fashion may
      effect stable and heritable silencing of the Ubx gene throughout advanced stages
      of development, thus mediating repression of this homeotic gene outside its realm
      of function.

PMID- 1354358
TI  - Multiple kinetic states underlying macroscopic M-currents in bullfrog sympathetic
      neurons.
AB  - M-current is a time- and voltage-dependent potassium current which is
      suppressible by muscarinic receptor activation. We have used curve fitting and
      noise analysis to determine if macroscopic M-currents deviate from a previously
      predicted simple two-state kinetic scheme. The M-current was best described by
      three kinetically distinct components: 'fast' (tau 0), 'intermediate' (tau 1) and
      'slow' (tau 2) time constants. The 'fast' (tau 0) and 'intermediate' (tau 1)
      components were identified from the spectra of M-current noise at potentials
      positive to the cells' resting membrane potential. The 'intermediate' (tau 1) and
      'slow' (tau 2) components were seen by curve fitting M-current deactivation
      currents. The 'intermediate' (tau 1) time constant was voltage dependent
      (decreasing e-fold in 23 mV), but voltage dependence of the 'fast' (tau 0) and
      'slow' (tau 2) components was not obvious. All kinetic components were sensitive
      to muscarine, with the 'intermediate' (tau 1) and 'slow' (tau 2) being equally
      so. These data suggest that all components may derive from the same channel
      population, and that the M-channel may have at least four kinetic states.

PMID- 1354359
TI  - Putative immunolocalization of the mechanoelectrical transduction channels in
      mammalian cochlear hair cells.
AB  - Hair cells bear an apical bundle of stereocilia arranged in serried rows.
      Deflection of the bundle controls the opening and closing of mechanoelectrical
      transduction channels, thereby altering the conductance across the apical plasma
      membrane. Two locations for these channels have been proposed in the bundle,
      either near the bases of the stereocilia or towards their tips. One hypothesis
      that is consistent with the latter possibility suggests that fine extracellular
      filaments, which run between the tips of the shorter stereocilia and the sides of
      the taller stereocilia behind, operate the channels. Determining the precise
      position of the channels is essential to test this hypothesis. We have therefore
      attempted to localize them immunocytochemically. Because hair-cell transduction
      is amiloride sensitive, the channels may have an amiloride-binding site
      associated with them. We have therefore used a polyclonal antibody raised against
      another amiloride-sensitive ion channel to hunt for them. This antibody
      recognizes a 62-64 kDa band in immunoblots of cochlear tissue, and produces
      discrete labelling in the hair bundle. This is most concentrated just below the
      tips of the shorter stereocilia, coinciding with a region of specialization in
      the closely apposed membranes of the short and tall stereocilia but not with
      either end of the tip link.

PMID- 1354357
TI  - Regional mapping of prion proteins in brain.
AB  - Scrapie is characterized by the accumulation of a protease-resistant isoform of
      the prion protein PrPSc. Limited proteolysis and chaotropes were used to map the
      distribution of PrPSc in cryostat sections of scrapie-infected brain blotted onto
      nitrocellulose membranes, designated histoblots. Proteolysis was omitted in order
      to map the cellular isoform of the prion protein (PrPC) in uninfected brains.
      Compared with immunohistochemistry, histoblots increased the sensitivity for
      PrPSc detection and showed different patterns of PrPSc accumulation. In Syrian
      hamsters with Sc237 scrapie, the most intense PrPSc signals occurred in sites
      with relatively little PrPC, suggesting that aberrant localization of prion
      protein may be an important feature in the pathogenesis of prion diseases.
      Immunostaining of PrPSc in white-matter tracts suggested that prions spread along
      neuroanatomical pathways. PrPSc immunostaining in histoblots was quantitated by
      densitometry, permitting assessment of the extent of PrPSc accumulation within
      specific structures. Histoblots were also useful in localizing PrPCJD and beta/A4
      amyloid peptide in the brains of patients with Creutzfeldt-Jakob disease and
      Alzheimer disease, respectively.

PMID- 1354361
TI  - Error-prone signalling.
AB  - The handicap principle of Zahavi is potentially of great importance to the study
      of biological communication. Existing models of the handicap principle, however,
      make the unrealistic assumption that communication is error free. It seems
      possible, therefore, that Zahavi's arguments do not apply to real signalling
      systems, in which some degree of error is inevitable. Here, we present a general
      evolutionarily stable strategy (ESS) model of the handicap principle which
      incorporates perceptual error. We show that, for a wide range of error functions,
      error-prone signalling systems must be honest at equilibrium. Perceptual error is
      thus unlikely to threaten the validity of the handicap principle. Our model
      represents a step towards greater realism, and also opens up new possibilities
      for biological signalling theory. Concurrent displays, direct perception of
      quality, and the evolution of 'amplifiers' and 'attenuators' are all probable
      features of real signalling systems, yet handicap models based on the assumption
      of error-free communication cannot accommodate these possibilities.

PMID- 1354360
TI  - Motor practice and neurophysiological adaptation in the cerebellum: a positron
      tomography study.
AB  - We have used positron tomography (PET) to demonstrate that some parts of the
      motor system exhibit physiological adaptation during the repeated performance of
      a simple motor task, but others do not. In contrast to the primary sensori-motor
      cortex, the cerebellum exhibits a decrease in physiological activation (increases
      in regional blood flow during performance) with practice. A new application of
      factorial experimental design to PET activation studies was used to make these
      measurements in four normal males. This design allowed adaptation to be examined
      by testing for an interaction between regional cerebral blood flow (rCBF)
      increases brought about by a motor task and the number of trials (time). These
      findings are interpreted as the neurophysiological correlates of synaptic changes
      in the cerebellum associated with motor learning in man.

PMID- 1354364
TI  - Oncogenes, anti-oncogenes and the immune response to cancer: a mathematical
      model.
AB  - We develop a mathematical model for the initial growth of a tumour after a
      mutation in which either an oncogene is expressed or an anti-oncogene (i.e.
      tumour suppressor gene) is lost. Our model incorporates mitotic control by
      several biochemicals, with quite different regulatory characteristics, and we
      consider mutations affecting the cellular response to these control mechanisms.
      Our mathematical representation of these mutations reflects the current
      understanding of the roles of oncogenes and anti-oncogenes in controlling cell
      proliferation. Numerical solutions of our model, for biologically relevant
      parameter values, show that the different types of mutations have quite different
      effects. Mutations affecting the cell response to chemical regulators, or
      resulting in autonomy from such regulators, cause an advancing wave of tumour
      cells and a receding wave of normal cells. By contrast, mutations affecting the
      production of a mitotic regulator cause a slow localized increase in the numbers
      of both normal and mutant cells. We extend our model to investigate the possible
      effects of an immune response to cancer by including a first order removal of
      mutant cells. When this removal rate exceeds a critical value, the immune system
      can suppress tumour growth; we derive an expression for this critical value as a
      function of the parameters characterizing the mutation. Our results suggest that
      the effectiveness of the immune response after an oncogenic mutation depends
      crucially on the way in which the mutation affects the biochemical control of
      cell division.

PMID- 1354362
TI  - Response to fibronectin-integrin interaction in leukaemia cells: delayed
      enhancing of a K+ current.
AB  - In murine erythroleukaemia cells, the response of ion channels was followed
      before and after contact with fibronectin-coated latex microspheres. Patch-clamp
      experiments in 'whole-cell' and in 'cell-attached' configurations showed that
      cell adhesion to fibronectin promoted plasma membrane hyperpolarization mediated
      by activation of potassium channels that were indistinguishable from calcium
      dependent potassium channels K(Ca) in these cells. K+ current increase began in 5
      6 min and was completed about 10 min after the first contact. The timecourse of
      this process recorded from 'whole-cell' was very similar to that followed in
      intact cells by observing the increase of single channel currents. The open
      probability of single channels in the patch increased after contact, revealing
      that this activation is propagated at distance from the adhesion site. The slow
      onset of the effect suggests the presence of a complex regulatory pathway between
      fibronectin-integrin binding and activation of potassium channels. Decreasing
      cytoplasmic free Ca2+ concentration to pCa 9 diminished, but did not inhibit, the
      response. The current induced by fibronectin was not blocked by apamin, alpha
      charybdotoxin or glibenclamide, but was abolished by high concentrations of
      tetraethylammonium (TEA). These data suggest for the first time the existence of
      a specific regulative connection between integrin receptors and ionic channels.

PMID- 1354363
TI  - Interaction of avidin with the lipoyl domains in the pyruvate dehydrogenase
      multienzyme complex: three-dimensional location and similarity to biotinyl
      domains in carboxylases.
AB  - Avidin can form intermolecular cross-links between particles of the pyruvate
      dehydrogenase multienzyme complex from various sources. Avidin does this by
      binding to lipoic acid-containing regions of the dihydrolipoamide
      acetyltransferase polypeptide chains that comprise the structural core of the
      complex. It is inferred that the lipoyl domains of the acetyltransferase chain
      extend outwards from the interior of the enzyme particle, interdigitating between
      the subunits of the other two enzymes bound peripherally in the assembled
      structure, with the lipoyl-lysine residues capable of reaching to within at least
      1-2 nm of the outer surface of the enzyme complex (diameter ca. 37 nm). The
      distribution of enzymic activities between different domains of the
      dihydrolipoamide acetyltransferase chain implies that considerable movement of
      the lipoyl domains is a feature of the catalytic activity of the enzyme complex.
      There is evidence that the lipoyl domain of the 2-oxo acid dehydrogenase
      complexes is similar in structure to a domain that binds the cofactor biotin,
      also in amide linkage with a specific lysine residue, in the biotin-dependent
      class of carboxylases.

PMID- 1354365
TI  - Amplification and rearrangement of a prokaryotic metallothionein locus smt in
      Synechococcus PCC 6301 selected for tolerance to cadmium.
AB  - Metal-tolerant cyanobacteria have been isolated from metal-polluted aquatic
      environments and also selected in culture, but no genes which confer metal
      tolerance have been described. To investigate the possibility that amplification
      of a prokaryotic metallothionein gene (smtA), or rearrangement of the smt locus,
      could be involved in the development of Cd tolerance in Synechococcus PCC 6301,
      Cd-tolerant lines were selected by stepwise adaptation of a Synechococcus
      culture. An increase in smtA gene copy number and the appearance of unique
      additional smtA restriction fragments (both larger and smaller) were detected in
      these tolerant lines (tolerant to 0.8 microM Cd, 1.3 microM Cd and 1.7 microM
      Cd). Stepwise adaptation was repeated by using a culture of Synechococcus PCC
      6301 inoculated from a single plated colony to obtain four new lines (tolerant to
      1.4 microM Cd, 1.8 microM Cd, 2.6 microM Cd and 3.2 microM Cd). Amplification of
      the smtA gene and development of unique smtA restriction fragments (larger and
      smaller) were once again detected in these tolerant lines. Amplification and
      rearrangement of the smt locus were only detected in the seven Cd-tolerant lines,
      with no evidence of amplification or rearrangement in the non-tolerant lines from
      which they were derived. As a control, another gene, psaE, was also monitored in
      these cell lines. There was no evidence of amplification or rearrangement of psaE
      in the non-tolerant or any of the Cd-tolerant lines.

PMID- 1354366
TI  - Isolation of deacetoxycephalosporin C from fermentation broths of Penicillium
      chrysogenum transformants: construction of a new fungal biosynthetic pathway.
AB  - Deacetoxycephalosporin C (DAOC), a precursor of cephalosporins excreted by
      Cephalosporium and Streptomyces species, has been produced in Penicillium
      chrysogenum transformed with DNA containing a hybrid penicillin N expandase gene
      (cefEh) and a hybrid isopenicillin N epimerase gene (cefDh). DAOC from a P.
      chrysogenum transformant was identified by ultraviolet light (UV), high
      performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) and
      mass spectrum analyses. P. chrysogenum transformed with DNA containing cefEh
      without cefDh did not produce DAOC. Untransformed P. chrysogenum produced
      penicillin V (phenoxymethylpenicillin) but not DAOC. Transformants also produced
      penicillin V but, in general, less than untransformed P. chrysogenum. The cefEh
      and cefDh genes were constructed by replacing the open reading frame (ORF) of
      cloned P. chrysogenum pcbC and penDE genes with the ORF of the Streptomyces
      clavuligerus expandase gene, cefE, and the ORF of the Streptomyces lipmanii
      epimerase gene, cefD, respectively. Analyses of representative transformants
      suggested that production of DAOC occurred via cefEh and cefDh genes stably
      integrated in the P. chrysogenum genome. DNA from untransformed P. chrysogenum
      did not hybridize to cefE or cefD gene probes.

PMID- 1354367
TI  - Dichromats detect colour-camouflaged objects that are not detected by
      trichromats.
AB  - To explain the surprisingly high frequency of congenital red-green colour
      blindness, the suggestion has been made that dichromats might be at an advantage
      in breaking certain kinds of colour camouflage. We have compared the performance
      of dichromats and normal observers in a task in which texture is camouflaged by
      colour. The texture elements in a target area differed in either orientation or
      size from the background elements. In one condition, the texture elements were
      all of the same colour; in the camouflage condition they were randomly coloured
      red or green. For trichromats, it proved to be more difficult to detect the
      target region in the camouflage condition, even though colour was completely
      irrelevant to the task. Dichromats (n = 7) did not show this effect, and indeed
      performed better than trichromats in the camouflage condition. We conclude that
      colour can interfere with segregation based upon texture, and that dichromats are
      less susceptible to such interference.

PMID- 1354368
TI  - Auditory processing of complex sounds: an overview.
AB  - The past 30 years has seen a remarkable development in our understanding of how
      the auditory system--particularly the peripheral system--processes complex
      sounds. Perhaps the most significant has been our understanding of the mechanisms
      underlying auditory frequency selectivity and their importance for normal and
      impaired auditory processing. Physiologically vulnerable cochlear filtering can
      account for many aspects of our normal and impaired psychophysical frequency
      selectivity with important consequences for the perception of complex sounds. For
      normal hearing, remarkable mechanisms in the organ of Corti, involving
      enhancement of mechanical tuning (in mammals probably by feedback of electro
      mechanically generated energy from the hair cells), produce exquisite tuning,
      reflected in the tuning properties of cochlear nerve fibres. Recent comparisons
      of physiological (cochlear nerve) and psychophysical frequency selectivity in the
      same species indicate that the ear's overall frequency selectivity can be
      accounted for by this cochlear filtering, at least in bandwidth terms. Because
      this cochlear filtering is physiologically vulnerable, it deteriorates in
      deleterious conditions of the cochlea--hypoxia, disease, drugs, noise
      overexposure, mechanical disturbance--and is reflected in impaired psychophysical
      frequency selectivity. This is a fundamental feature of sensorineural hearing
      loss of cochlear origin, and is of diagnostic value. This cochlear filtering,
      particularly as reflected in the temporal patterns of cochlear fibres to complex
      sounds, is remarkably robust over a wide range of stimulus levels. Furthermore,
      cochlear filtering properties are a prime determinant of the 'place' and 'time'
      coding of frequency at the cochlear nerve level, both of which appear to be
      involved in pitch perception. The problem of how the place and time coding of
      complex sounds is effected over the ear's remarkably wide dynamic range is
      briefly addressed. In the auditory brainstem, particularly the dorsal cochlear
      nucleus, are inhibitory mechanisms responsible for enhancing the spectral and
      temporal contrasts in complex sounds. These mechanisms are now being dissected
      neuropharmacologically. At the cortical level, mechanisms are evident that are
      capable of abstracting biologically relevant features of complex sounds.
      Fundamental studies of how the auditory system encodes and processes complex
      sounds are vital to promising recent applications in the diagnosis and
      rehabilitation of the hearing impaired.

PMID- 1354370
TI  - Sensory transduction and frequency selectivity in the basal turn of the guinea
      pig cochlea.
AB  - Receptor potentials recorded from outer hair cells (OHC) and inner hair cells
      (IHC) in the basal high-frequency turn were compared. The DC component of the IHC
      receptor potential is maximized to ensure that IHCS can signal a voltage response
      to high-frequency tones. The OHC DC component is minimized so that OHCS transduce
      in the most sensitive region of their operating range. The phase and magnitude of
      OHC receptor potentials were recorded as an indicator of the magnitude and phase
      of the energy which is fed back to the basilar membrane to provide the basis for
      the sharp tuning and fine sensitivity of the cochlea to tones. IHC receptor
      potentials were recorded to assess the net effect of the feedback on the
      mechanics of the cochlea. It was concluded that OHCS generate feedback which
      enhances the IHC responses only at the best frequency. At frequencies below CF,
      IHC DC responses are elicited only when the OHC AC responses begin to saturate.

PMID- 1354369
TI  - Basilar membrane responses to two-tone and broadband stimuli.
AB  - The responses to sound of mammalian cochlear neurons exhibit many nonlinearities,
      some of which (such as two-tone rate suppression and intermodulation distortion)
      are highly frequency specific, being strongly tuned to the characteristic
      frequency (CF) of the neuron. With the goal of establishing the cochlear origin
      of these auditory-nerve nonlinearities, mechanical responses to clicks and to
      pairs of tones were studied in relatively healthy chinchilla cochleae at a basal
      site of the basilar membrane with CF of 8-10 kHz. Responses were also obtained in
      cochleae in which hair cell receptor potentials were reduced by systemic
      furosemide injection. Vibrations were recorded using either the Mossbauer
      technique or laser Doppler-shift velocimetry. Responses to tone pairs contained
      intermodulation distortion products whose magnitudes as a function of stimulus
      frequency and intensity were comparable to those of distortion products in
      cochlear afferent responses. Responses to CF tones could be selectively
      suppressed by tones with frequency either higher or lower than CF; in most
      respects, mechanical two-tone suppression resembled rate suppression in cochlear
      afferents. Responses to clicks displayed a CF-specific compressive nonlinearity,
      similar to that present in responses to single tones, which could be profoundly
      and selectively reduced by furosemide. The present findings firmly support the
      hypothesis that all CF-specific nonlinearities present in the auditory nerve
      originate in analogous phenomena of basilar membrane vibration. However, because
      of their lability, it is almost certain that the mechanical nonlinearities
      themselves originate in outer hair cells.

PMID- 1354371
TI  - Evidence that adaptation of suppression cannot account for auditory enhancement
      or enhanced forward masking.
AB  - Delaying the onset of a signal relative to the onset of a simultaneous notched
      masker often improves the ability of listeners to 'hear out' the signal at both
      threshold and suprathreshold levels. Viemeister & Bacon (J. acoust. Soc. Am., 71,
      1502-1507 (1982)) suggested that such auditory enhancement effects could be
      accounted for if the suppression produced by the masker on the signal frequency
      adapted, thereby releasing the signal from suppression. In support of their
      hypothesis, Viemeister & Bacon reported that a masker preceded by an enhancer
      having no component at the signal frequency produced more forward masking than
      did the masker by itself. Here evidence is provided from five new experiments
      showing that adaptation of psychophysical two-tone suppression is inadequate to
      account either for auditory enhancement effects or for the enhanced forward
      masking demonstrated by Viemeister & Bacon.

PMID- 1354372
TI  - Masking release for gap detection.
AB  - In random noise, masking is influenced almost entirely by noise components in a
      narrow band around the signal frequency. However, when the noise is not random,
      but has a modulation pattern which is coherent across frequency, noise components
      relatively remote from the signal frequency can actually produce a release from
      masking. This masking release has been called comodulation masking release (CMR).
      The present research investigated whether a similar release from masking occurs
      in the analysis of a suprathreshold signal. Specifically, the ability to detect
      the presence of a temporal gap was investigated in conditions which do and do not
      result in CMR for detection threshold. Similar conditions were investigated for
      the masking level difference (a binaural masking release phenomenon). The results
      indicated that suprathreshold masking release for gap detection occurred for both
      the masking-level difference (MLD) and for CMR. However, masking release for gap
      detection was generally smaller than that obtained for detection threshold. The
      largest gap detection masking release effects obtained corresponded to relatively
      low levels of stimulation, where gap detection was relatively poor.

PMID- 1354373
TI  - Modulation discrimination interference and auditory grouping.
AB  - The detection of a change in the modulation pattern of a (target) carrier
      frequency, fc (for example a change in the depth of amplitude or frequency
      modulation, AM or FM) can be adversely affected by the presence of other
      modulated sounds (maskers) at frequencies remote from fc, an effect called
      modulation discrimination interference (MDI). MDI cannot be explained in terms of
      interaction of the sounds in the peripheral auditory system. It may result partly
      from a tendency for sounds which are modulated in a similar way to be
      perceptually 'grouped', i.e. heard as a single sound. To test this idea, MDI for
      the detection of a change in AM depth was measured as a function of stimulus
      variables known to affect perceptual grouping, namely overall duration and onset
      and offset asynchrony between the masking and target sounds. In parallel
      experiments, subjects were presented with a series of pairs of sounds, the target
      alone and the target with maskers, and were asked to rate how clearly the
      modulation of the target could be heard in the complex mixture. The results
      suggest that two factors contribute to MDI. One factor is difficulty in hearing a
      pitch corresponding to the target frequency. This factor appears to be strongly
      affected by perceptual grouping. Its effects can be reduced or abolished by
      asynchronous gating of the target and masker. The second factor is a specific
      difficulty in hearing the modulation of the target, or in distinguishing that
      modulation from the modulation of other sounds that are present. This factor has
      effects even under conditions promoting perceptual segregation of the target and
      masker.

PMID- 1354374
TI  - The psychophysics of concurrent sound segregation.
AB  - To perceptually separate concurrent complex sounds, normally hearing listeners
      simultaneously combine information across a wide range of frequency components.
      Three psychoacoustical experiments are described which investigate different
      forms of this across-frequency processing. The first two experiments investigate
      the role of coherence of frequency modulation (FM) between widely separated
      frequency components of a complex sound. The first experiment bolsters existing
      evidence that, for harmonic sounds, listeners can discriminate coherent from
      incoherent FM, but only by detecting the mistuning that arises from incoherent
      FM. The second demonstrates that, for inharmonic sounds, coherence of FM has no
      effect on the phenomenon of modulation detection interference (see Moore &
      Shailer, this symposium) once within-channel cues (combination tones and beating)
      are masked by background noise. It is concluded that there is not an across
      frequency mechanism specific to the detection of FM incoherence. The third
      experiment investigates the extent to which the detection of mistuning of one
      component of a harmonic complex is impaired by an interfering sound (the
      'interferer') with a frequency spectrum similar to that of the mistuned
      component. When the interferer is gated on and off with the harmonic complex, it
      has only a small effect provided that its level is more than 3 dB below that of
      the target. However, when the interferer starts before and ends after the
      complex, thresholds are elevated more, and this elevation occurs even for low
      level interferers. Explanations of this effect in terms of adaptation and of
      auditory streaming are discussed.

PMID- 1354375
TI  - Auditory segregation of competing voices: absence of effects of FM or AM
      coherence.
AB  - Four experiments sought evidence that listeners can use coherent changes in the
      frequency or amplitude of harmonics to segregate concurrent vowels. Segregation
      was not helped by giving the harmonics of competing vowels different patterns of
      frequency or amplitude modulation. However, modulating the frequencies of the
      components of one vowel was beneficial when the other vowel was not modulated,
      provided that both vowels were composed of components placed randomly in
      frequency. In addition, staggering the onsets of the two vowels, so that the
      amplitude of one vowel increased abruptly while the amplitude of the other was
      stationary, was also beneficial. Thus, the results demonstrate that listeners can
      group changing harmonics and can segregate them from stationary harmonics, but
      cannot use coherence of change to separate two sets of changing harmonics.

PMID- 1354376
TI  - Temporal information in speech: acoustic, auditory and linguistic aspects.
AB  - The temporal properties of speech appear to play a more important role in
      linguistic contrasts than has hitherto been appreciated. Therefore, a new
      framework for describing the acoustic structure of speech based purely on
      temporal aspects has been developed. From this point of view, speech can be said
      to be comprised of three main temporal features, based on dominant fluctuation
      rates: envelope, periodicity, and fine-structure. Each feature has distinct
      acoustic manifestations, auditory and perceptual correlates, and roles in
      linguistic contrasts. The applicability of this three-featured temporal system is
      discussed in relation to hearing-impaired and normal listeners.

PMID- 1354377
TI  - Pitch related to spectral edges of broadband signals.
AB  - A complex tone often evokes a pitch sensation associated with its extreme
      spectral components, besides the holistic pitch associated with its fundamental
      frequency. We studied the edge pitch created at the upper spectral edge of
      complexes with a low-pass spectrum by asking subjects to adjust the frequency of
      a sinusoidal comparison tone to the perceived pitch. Measurements were performed
      for different values of the fundamental frequency and of the upper frequency of
      the complex as well as for three different phase relations of the harmonic
      components. For a wide range of these parameters the subjects could adjust the
      comparison tone with a high accuracy, measured as the standard deviation of
      repeated adjustments, to a frequency close to the nominal edge frequency. The
      detailed dependence of the matching accuracy on temporal parameters of the
      harmonic complexes suggests that the perception of the edge pitch in harmonic
      signals is related to the temporal resolution of the hearing system. This
      resolution depends primarily on the time constants of basilar-membrane filters
      and on additional limitations due to neuronal processes.

PMID- 1354378
TI  - Perception of timbral analogies.
AB  - Recent studies have investigated the structure of perceptual relations among
      musical instrument timbres by multidimensional scaling (MDS) techniques. These
      studies have employed both acoustically produced tones and digitally synthesized
      imitations and hybrids of acoustic instrument tones. The analyses of
      dissimilarity ratings for all pairs of a set of tones are usually represented as
      geometrical structures in a two- or three-dimensional Euclidean space in which
      the shared 'perceptual' axes are shown to have a qualitative correspondence to
      acoustic properties such as spectral energy distribution, onset characteristics
      and degree of change in spectral distribution over the duration of the tone. The
      present study took as a point of departure a MDS analysis for complex, synthetic
      tones with the aim of testing whether musician and non-musician listeners used
      the relations defined by the perceptual space to perform an analogies task of the
      sort: timbre A is to timbre B as timbre C is to which of two possible timbres, D
      or D'? A parallelogram model was used to select the D timbres: if the relation
      between A and B is represented as a vector with both magnitude and direction
      components, then the appropriate D should form a vector with C having similar
      magnitude and direction in the timbre space. Aside from conceptual difficulties
      with the task for both non-musicians and composers, choices for both groups
      provide support for the parallelogram model indicating a capacity in listeners to
      perceive abstract relations among the timbres of complex sounds without specific
      training in such a task.

PMID- 1354379
TI  - Some new pitch paradoxes and their implications.
AB  - This paper explores two new paradoxical sound patterns. The tones used to produce
      these patterns consist of six octave-related harmonics, whose amplitudes are
      scaled by a bell-shaped spectral envelope; these tones are clearly defined in
      terms of pitch class (C, C#, D, and so on) but are poorly defined in terms of
      height. One pattern consists of two tones that are separated by a half-octave. It
      is heard as ascending when played in one key, yet as descending when played in a
      different key. Further, when the pattern is played in any one key it is heard as
      ascending by some listeners but as descending by others (the tritone paradox).
      Another pattern that consists of simultaneous pairs of tones displays related
      properties (the semitone paradox). It is shown that the way the tritone paradox
      is perceived correlates with the speech characteristics of the listener,
      including his or her linguistic dialect. The findings suggest that the same,
      culturally acquired representation of pitch classes influences both speech
      production and also perception of this musical pattern.

PMID- 1354380
TI  - Coding of envelope modulation in the auditory nerve and anteroventral cochlear
      nucleus.
AB  - We have investigated responses of the auditory nerve fibres (ANFS) and
      anteroventral cochlear nucleus (AVCN) units to narrowband 'single-formant'
      stimuli (SFSS). We found that low and medium spontaneous rate (SR) ANFS maintain
      greater amplitude modulation (AM) in their responses at high sound levels than do
      high SR units when sound level is considered in dB SPL. However, this
      partitioning of high and low SR units disappears if sound level is considered in
      dB relative to unit threshold. Stimuli with carrier frequencies away from unit
      best frequency (BF) were found to generate higher AM in responses at high sound
      levels than that observed even in most low and medium SR units for stimuli with
      carrier frequencies near BF. AVCN units were shown to have increased modulation
      depth in their responses when compared with high SR ANFS with similar BFS and to
      have increased or comparable modulation depth when compared with low SR ANFS. At
      sound levels where AM almost completely disappears in high SR ANFS, most AVCN
      units we studied still show significant AM in their responses. Using a dendritic
      model, we investigated possible mechanisms of enhanced AM in AVCN units,
      including the convergence of inputs from different SR groups of ANFS and a
      postsynaptic threshold mechanism in the soma.

PMID- 1354381
TI  - Modelling the sensitivity of cells in the anteroventral cochlear nucleus to
      spatiotemporal discharge patterns.
AB  - This study investigates a potential mechanism for the processing of acoustic
      information that is encoded in the spatiotemporal discharge patterns of auditory
      nerve (AN) fibres. Recent physiological evidence has demonstrated that some low
      frequency cells in the anteroventral cochlear nucleus (AVCN) are sensitive to
      manipulations of the phase spectrum of complex sounds (Carney 1990b). These
      manipulations result in systematic changes in the spatiotemporal discharge
      patterns across groups of low-frequency AN fibres having different characteristic
      frequencies (CFS). One interpretation of these results is that these neurons in
      the AVCN receive convergent inputs from AN fibres with different CFS, and that
      the cells perform a coincidence detection or cross-correlation upon their inputs.
      This report presents a model that was developed to test this interpretation.

PMID- 1354382
TI  - Neural organization and responses to complex stimuli in the dorsal cochlear
      nucleus.
AB  - The dorsal division of the cochlear nucleus (DCN) is the most complex of its
      subdivisions in terms of both anatomical organization and physiological response
      types. Hypotheses about the functional role of the DCN in hearing are as yet
      primitive, in part because the organizational complexity of the DCN has made
      development of a comprehensive and predictive model of its input-output
      processing difficult. The responses of DCN cells to complex stimuli, especially
      filtered noise, are interesting because they demonstrate properties that cannot
      be predicted, without further assumptions, from responses to narrow band stimuli,
      such as tones. In this paper, we discuss the functional organization of the DCN,
      i.e. the morphological organization of synaptic connections within the nucleus
      and the nature of synaptic interactions between its cells. We then discuss the
      responses of DCN principal cells to filtered noise stimuli that model the
      spectral sound localization cues produced by the pinna. These data imply that the
      DCN plays a role in interpreting sound localization cues; supporting evidence for
      such a role is discussed.

PMID- 1354383
TI  - Binaural masking and sensitivity to interaural delay in the inferior colliculus.
AB  - The binaural masking level difference (BMLD) is a psychophysical effect whereby
      signals masked by a noise at one ear become unmasked by sounds reaching the
      other. BMLD effects are largest at low frequencies where they depend on signal
      phase, suggesting that part of the physiological mechanism responsible for the
      BMLD resides in cells that are sensitive to interaural time disparities. We have
      investigated a physiological basis for unmasking in the responses of delay
      sensitive cells in the central nucleus of the inferior colliculus in
      anaesthetized guinea pigs. The masking effects of a binaurally presented noise,
      as a function of the masker delay, were quantified by measuring the number of
      discharges synchronized to the signal, and by measuring the masked threshold. The
      noise level for masking was lowest at the best delay for the noise. The mean
      magnitude of the unmasking across our neural population was similar to the human
      psychophysical BMLD under the same signal and masker conditions.

PMID- 1354384
TI  - Philosophy and stimulus design for neuroethology of complex-sound processing.
AB  - In research on the neural mechanisms for the processing of biologically important
      sounds such as species-specific sounds and sounds produced by prey and predators,
      it is necessary to study responses of central auditory neurons to biologically
      important sounds, information-bearing elements (IBEs) in them, and tone bursts.
      The tone bursts or constant-frequency (CF) components can be an IBE in many
      species of animals. Information-bearing parameters characterizing these sounds
      must be systematically varied, and tuning of neurons to individual parameters
      must be studied. The measurement of a tuning curve must be performed not only for
      excitatory responses, but also for inhibitory and facilitative responses, if any.
      The selectivity of a neuron to a particular type of sound must be tested for
      whether it is level-tolerant. Responses to complex sounds can probably be
      explained on the basis of those to IBEs and tone bursts, so that the use of the
      tone bursts, even though they are not IBEs, is as essential as that of the
      biologically important sounds.

PMID- 1354385
TI  - Molecular characteristics of excitatory amino acid receptors.

PMID- 1354387
TI  - Neurotransmitter actions in the thalamus and cerebral cortex and their role in
      neuromodulation of thalamocortical activity.

PMID- 1354386
TI  - Effect of ammonium ions on synaptic transmission in the mammalian central nervous
      system.
AB  - It is not surprising that a compound with such unique properties as NH3/NH4+,
      should have a large variety of biochemical and neurological effects and to find
      itself implicated in many pathological conditions. Its undissociated (NH3) or
      dissociated (NH4+) forms, having different physicochemical properties, enter
      neurons and other cells through differing pathways. These two forms then change
      internal pH in opposite directions, and initiate a variety of regulatory
      processes that attempt to overcome these pH changes. In addition, ammonia has a
      central role in normal intermediary metabolism, and when present in excess, it
      can disturb reversible reactions in which it participates. The challenge in
      interpreting these various observations lies in the difficulty in assigning to
      them a role in the generation of symptoms seen in experimental and clinical
      hyperammonemias. In this review we have attempted to summarize information
      available on the effects of ammonium ions on synaptic transmission, a central
      process in nervous system function. Evidence has been presented to show that
      ammonium ions, in pathologically relevant concentrations, interfere with
      glutamatergic excitatory transmission, not by decreasing the release of
      glutamate, but by preventing its action on post-synaptic AMPA receptors.
      Furthermore, NH4+ depolarizes neurons to a variable degree, without consistently
      changing membrane resistance, probably by reducing [K+]i. A decrease in EK+ may
      also be responsible for decreasing the effectiveness of the outward chloride
      pump, thus explaining the well known inhibitory effect of NH4+ on the
      hyperpolarizing IPSP. There is a consensus of opinion that chronic hyperammonemia
      increases 5HT turnover and this may be responsible for altered sleep patterns
      seen in hepatic encephalopathy. There does not seem to be a consistent effect on
      catecholaminergic transmission in hyperammonemias. However, chronic
      hyperammonemia causes pathological changes in perineuronal astrocytes, which may
      lead to a reduced uptake of released glutamate and a decreased detoxification of
      ammonia by the brain. Chronic moderate increase in extracellular glutamate
      results in a down-regulation of NMDA receptors, while the decreased
      detoxification of ammonia makes the central nervous system more vulnerable to a
      sudden hyperammonemia, due, for instance, to an increased dietary intake of
      proteins or to gastrointestinal bleeding in patients with liver disease. Clearly,
      data summarized in this review represent only the beginning in the elucidation of
      the mechanism of ammonia neurotoxicity. It should help, we hope, to direct future
      investigations towards some of the questions that need to be answered.

PMID- 1354389
TI  - [XXXII Congress of Stomatology and Maxillofacial Surgery. Strasbourg, October 1
      5, 1991].

PMID- 1354388
TI  - [Hepatotoxicity caused by glafenin. Apropos of 2 cases].

PMID- 1354390
TI  - Non-MHC-restricted T-cell interaction with B cells: role of the T-cell receptor.
AB  - Non-specific antibody production usually accompanies the T-cell-regulated B-cell
      response. In this paper the mechanisms involved in non-MHC-restricted T-B-cell
      interaction were studied. As previously shown for NK cells, activated B cells
      induce IFN-gamma and TNF alpha production in non-MHC-restricted cytotoxic T
      lymphocytes (NrCTL). Using an in vitro model system, we demonstrate that direct
      cell-cell interactions are required to induce these cytokines in NrCTL. Receptor
      ligand systems involved are leucocyte function antigen-1/intercellular adhesion
      molecule-1 (LFA-1/ICAM-1)(CD11a, CD18/CD54), T11/LFA-3 (CD2/CD58), and the
      clonotypic T-cell receptor (TCR) structure NKTa of JT9/JT10 with its non-MHC
      related target antigen TNKtar (4F2). Cytokine production can be induced by
      activating monoclonal antibodies against CD2R. Antibodies against the clonotypic
      TCR (NKTa) or CD3 had no cytokine-inducing effect on NrCTL cultured alone, but
      were able to retrieve the effect of blocking the target antigen on co-cultured B
      cells. We could further demonstrate that the inhibition of the TCR/target antigen
      interaction could be overcome by close cell-cell contact culture conditions. From
      these findings it is concluded that the role of the TCR in non-MHC-restricted
      cell-cell interaction is to facilitate LFA-1/ICAM-1-mediated effector target
      adhesion in a specific way rather than to mediate direct activating signals upon
      lymphokine production or cytotoxicity.

PMID- 1354391
TI  - Control of Trypanosoma cruzi infection in mice deprived of T-cell help.
AB  - The role of CD4+ T lymphocytes in the resistance of BALB/c mice to Trypanosoma
      cruzi was examined by in vivo depletion using monoclonal anti-CD4 antibodies
      (MoAbs). When the administration of MoAbs was initiated 2 days before, or 5 to 12
      days after the infection (dpi) with 50 bloodstream-form trypomastigotes of the
      Tulahuen strain, mice showed an enhanced susceptibility to the parasite. Specific
      IgG, but not IgM responses, were inhibited in anti-CD4-treated and infected mice.
      However, when anti-CD4 treatment of mice was delayed until the 8th week of
      infection, neither a reactivation of the infection as determined by mortality or
      parasitaemia, nor a modulation of the titre of anti-T. cruzi IgG antibodies was
      detected. Furthermore, mice chronically infected with T. cruzi and deprived of
      CD4+ T cells resisted the challenge with 50,000 trypomastigotes (approximately
      1000 LD50). Secondary antibody responses against parasite antigens were inhibited
      after in vitro depletion of CD4+ cells in chronically infected mice before
      boosting with T. cruzi antigens. However, recipients of CD4 or T-cell-depleted
      spleen cells from mice chronically infected with T. cruzi were protected when
      challenged with the parasite. The possibility that the parasite control is
      maintained by long-lived B cells capable of rapid differentiation into IgG
      secreting plasma cells in the absence of T helper cells is discussed considering
      the present data.

PMID- 1354392
TI  - Treatment of rheumatoid arthritis with single dose or weekly pulses of chimaeric
      anti-CD4 monoclonal antibody.
AB  - The aetiology of rheumatoid arthritis is unknown but CD4+ T cells are known to be
      involved in its pathogenesis. Because of this, anti-CD4 monoclonal antibody has
      been used in open studies with clinical benefit in up to 60% of patients. We have
      used a chimaeric anti-CD4 monoclonal antibody (cM-T412, Centocor) in a
      randomized, double-blinded, placebo controlled trial as treatment for rheumatoid
      arthritis. Nine patients with active rheumatoid arthritis resistant to
      traditional disease-modifying drugs were recruited. Four received an intravenous
      50 mg bolus of antibody, and three received 50 mg weekly for four consecutive
      weeks. Two patients received placebo. Despite a marked reduction (P less than
      0.001) in peripheral blood CD4+ lymphocytes, there was no significant clinical
      improvement in any of these patients. The decrease in CD4+ lymphocyte number
      lasted one week after a single 50 mg dose of cM-T412 but was more prolonged in
      the patients who received four infusions. CD8+ T cells, CD16+ cytotoxic cells and
      CD14+ monocytes showed only a transient reduction. It may be concluded that the
      therapeutic efficacy of anti-CD4 therapy is not directly related to CD4+ T-cell
      lymphopenia.

PMID- 1354393
TI  - Differential display of eukaryotic messenger RNA by means of the polymerase chain
      reaction.
AB  - Effective methods are needed to identify and isolate those genes that are
      differentially expressed in various cells or under altered conditions. This
      report describes a method to separate and clone individual messenger RNAs (mRNAs)
      by means of the polymerase chain reaction. The key element is to use a set of
      oligonucleotide primers, one being anchored to the polyadenylate tail of a subset
      of mRNAs, the other being short and arbitrary in sequence so that it anneals at
      different positions relative to the first primer. The mRNA subpopulations defined
      by these primer pairs were amplified after reverse transcription and resolved on
      a DNA sequencing gel. When multiple primer sets were used, reproducible patterns
      of amplified complementary DNA fragments were obtained that showed strong
      dependence on sequence specificity of either primer.

PMID- 1354394
TI  - A point mutation of the alpha 2-adrenoceptor that blocks coupling to potassium
      but not calcium currents.
AB  - The alpha 2A-adrenergic receptor (adrenoceptor) was stably expressed in AtT20
      mouse pituitary tumor cells; adrenoceptor agonists inhibited adenylyl cyclase,
      inhibited voltage-dependent calcium currents, and increased inwardly rectifying
      potassium currents. An aspartic acid residue (Asp79) highly conserved among
      guanine nucleotide-binding protein (G protein)-coupled receptors was mutated to
      asparagine; in cells transfected with the mutant alpha 2-receptor, agonists
      inhibited adenylyl cyclase and calcium currents but did not increase potassium
      currents. Because distinct G proteins appear to couple adrenoceptors to potassium
      and calcium currents, the present findings suggest that the mutant alpha 2
      adrenoceptor cannot achieve the conformation necessary to activate G proteins
      that mediate potassium channel activation.

PMID- 1354395
TI  - [The mosquito hypothetically considered as an agent of yellow fever transmission.
      1881].

PMID- 1354396
TI  - Membrane properties of identified mesencephalic dopamine neurons in primary
      dissociated cell culture.
AB  - Dopamine (DA)-containing neurons in primary dissociated cell cultures derived
      from the embryonic mouse mesencephalon (day E13) were studied by histochemical
      and electrophysiological techniques. DA neurons exhibited two distinct
      morphologies, fusiform and multipolar, tended to reside in groups and organize
      dendrites into common fascicles. While these neurons expressed the cell-surface
      marker acetylcholinesterase, the presence of this enzyme could not be used to
      identify DA neurons unequivocally, since it was also observed in nondopaminergic
      cells. Neurons were therefore identified as DA by their distinct morphology, and
      this identification was validated with a double-labeling procedure that entailed
      the intracellular deposition of a fluorescent dye (Lucifer yellow or ethidium
      bromide), followed by processing for tyrosine hydroxylase immunocytochemistry. DA
      neurons identified in this manner were observed to have resting membrane
      potentials between -50 and -75 mV, input resistances of 50-360 M omega, and
      membrane time constants of 4.1-14.1 msec. Forty-seven percent of these cells
      displayed spontaneous activity that was irregular in nature and often contained
      bursts (burst length was between two and six action potentials). The DA neurons
      displayed a variety of ionic conductances, including (1) a Na+ conductance (gNa)
      that underlies the action potential, (2) Ca2+ conductances (gCa) that mediate the
      nonsomatic low- and high-threshold spikes observed, and (3) at least three K+
      conductances (gK). Voltage-clamp analysis revealed several distinct transmembrane
      ionic currents, including (1) a large, rapidly inactivating tetrodotoxin
      sensitive inward Na+ current (INa), (2) a 4-aminopyridine-sensitive, transient
      early outward K+ current that required a conditioning hyperpolarization of the
      membrane to be activated by a subsequent depolarization (A-current, IA), (3) a
      slowly developing inward current that was seen only after a conditioning
      hyperpolarization of the membrane and that was dependent on the presence of
      external Ca2+ ions (ICa), and (4) a late-onset, noninactivating K+ current.
      Between 25% and 54% of the late-onset K+ current was Ca(2+)-dependent and was not
      affected by tetraethylammonium ions. This current was termed IAHP. The remaining
      current was not sensitive to changes in the extracellular Ca2+ concentration but
      was blocked by external tetraethylammonium. This current was termed IK. The
      direct pressure application of DA (1-200 microM) onto the soma dose-dependently
      hyperpolarized these neurons; this effect was potentiated by the presence of the
      catecholamine reuptake blocker cocaine hydrochloride (10-200 microM). Under
      voltage-clamp conditions, DA was observed to increase IK significantly and had
      little effect on IAHP.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1354397
TI  - Induction of long-term potentiation in the basolateral amygdala does not depend
      on NMDA receptor activation.
AB  - Long-term potentiation (LTP) can be induced in the lateral and basolateral
      amygdala by stimulating synaptic afferents in the external capsule (EC). We
      examined the sensitivity of amygdaloid LTP to the NMDA receptor antagonist 2
      amino-5-phosphonopentanoate (AP5), which is known to block LTP induction in the
      Schaffer collateral/CA1 synapses in the hippocampus. While relatively high
      concentrations (100 microM) of DL-AP5 were effective in preventing LTP induction
      in the lateral and basolateral amygdala in vitro, the same concentrations also
      significantly depressed synaptic responses to low-frequency stimulation.
      Furthermore, at 50 microM, a concentration sufficient to block both synaptic
      responses mediated by NMDA receptors and LTP induction in the hippocampus and
      neocortex, AP5 did not affect the probability of inducing LTP in the amygdala.
      Application of 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), which
      blocks non-NMDA excitatory amino acid receptors, reduced the monosynaptic
      response to EC stimulation by 85%. The remaining CNQX-insensitive response did
      not appear to be mediated by NMDA-type receptors, since it was not reduced by 50
      or 100 microM AP5, and showed none of the voltage sensitivity characteristic of
      NMDA responses. These data suggest that while the induction of LTP in the
      amygdala produced by EC stimulation is blocked by high doses of AP5, plasticity
      at these synapses probably does not require activation of NMDA receptors.

PMID- 1354398
TI  - Microiontophoretic studies of the effects of D-1 and D-2 receptor agonists on
      type I caudate nucleus neurons: lack of synergistic interaction.
AB  - Several lines of evidence have suggested there may be a physiologically relevant
      form of synergistic interaction between D-1 and D-2 dopamine (DA) receptors
      located on postsynaptic neurons in the forebrain that receive a dopaminergic
      innervation. Because of the theoretical importance of such an interaction with
      respect to understanding the normal physiology of dopaminergic systems, we
      evaluated effects of D-1 and D-2 selective agonists, applied
      microiontophoretically, on the spontaneous electrical activity of a single,
      identifiable subpopulation of neurons within the caudate nucleus, the type I
      striatal neuron, in locally anesthetized, gallamine-paralyzed rats. It was
      observed that the D-2 receptor agonist quinpirole (QUIN) produced biphasic
      effects on cell firing rate. Low ejection currents significantly increased firing
      rate, while higher currents produced an inhibition. Similar effects were observed
      for the D-1 agonists SKF 38393; however, the overall excitations observed at low
      ejection currents were far less than those observed for QUIN. When these two
      agonists were applied concurrently, a simple additive effect (but not synergism)
      was always observed. The acute reduction of striatal levels of DA, by as much as
      84% (with pretreatment with alpha-methyl-p-tyrosine, AMPT), did not alter the
      responsiveness of type I striatal neurons to the DA receptor agonists applied
      alone or in combination. These observed effects were not altered either by
      chloral hydrate anesthesia (in which glutamate-driven activity was studied) or by
      a more severe depletion of striatal DA levels (98% depletion produced by combined
      pretreatment with AMPT and reserpine).

PMID- 1354399
TI  - Differential modulation by dopamine of responses evoked by excitatory amino acids
      in human cortex.
AB  - The responses of human neocortical neurons to iontophoretic application of
      excitatory amino acids and their modulation by dopamine (DA) were studied in
      vitro. Brain slices were obtained from children undergoing surgery for
      intractable epilepsy. Application of N-methyl-D-aspartate (NMDA) to the slices
      induced slow depolarizations accompanied by decreased input conductances and
      sustained action potentials in cortical neurons. Glutamate produced rapid
      depolarizations and firing with few changes in input conductances. Quisqualate
      also induced depolarization and firing, but input conductances increased during
      the rising phase of the membrane depolarization. Iontophoretic application of DA
      alone produced no change in membrane potential or input conductance. However,
      when DA was applied in conjunction with the excitatory amino acids, it produced
      contrasting effects. With either bath application of DA or when iontophoresis of
      DA preceded application of NMDA, the amplitude of the membrane depolarizations
      and the number of action potentials were increased, whereas the latency of these
      responses decreased. In contrast, DA decreased the amplitude of the
      depolarizations and the number of action potentials evoked by glutamate or
      quisqualate. The fact that DA affects responses to NMDA and glutamate or
      quisqualate in opposite directions is of considerable importance to the
      understanding of cellular mechanisms of neuromodulation and the role of DA in
      cognitive processing and in epilepsy.

PMID- 1354401
TI  - Modification of atracurium or vecuronium blockade and their reversal by
      succinylcholine in the cat.
AB  - The interaction between succinylcholine (SCC) and non-depolarizers, atracurium or
      vecuronium was investigated in 36 cats of either sex using the sciatic nerve
      anterior tibialis muscle preparation. Additionally, the relation of SCC to
      pseudocholinesterase activity was examined. The duration of action of vecuronium
      (6.5 +/- 1.3 to 7.3 +/- 2.2 minutes) in cats pretreated with SCC was greater than
      those (2.0 +/- 0.6 minutes) in non-pretreated cats. However, SCC had no influence
      on the duration of atracurium. The serum pseudocholinesterase activity was
      decreased after the injection of atracurium or neostigmine in contrast to
      vecuronium. The authors conclude that the prior administration of SCC prolongs
      the duration of vecuronium but not that of atracurium, and pseudocholinesterase
      activity is not related to the prolonging effect of SCC.

PMID- 1354400
TI  - Annulate lamellae in a large cell lung carcinoma cell line with high expression
      of tyrosine kinase receptor and proto-oncogenes.
AB  - The morphology, karyotype, in vitro growth properties, and expression of tyrosine
      kinase receptors and proto-oncogenes are reported for a newly established large
      cell undifferentiated lung carcinoma cell line (RVH-6849). The results were
      analyzed concomitantly with those for two well-established cell lines from an
      adenocarcinoma of the lung (A549) and a squamous cell carcinoma (A431). All three
      cell lines demonstrated common ultrastructural features of epithelial cells, but
      only RVH-6849 had frequent aggregates of centrioles and annulate lamellae (AL)
      and was polyploid, having five to seven copies of chromosome 7 by karyotype
      analysis. All three cell lines expressed transforming growth factor alpha (TGF
      alpha), epidermal growth factor receptor (EGFR), c-erb B-2, and c-met genes. RVH
      6849 cells, however, expressed the most messenger RNA (mRNA) for TGF-alpha, c-erb
      B-2, and c-met. Only EGFR mRNA was expressed more in the other two cell lines,
      especially in A431 cells. AL represent an exaggerated form of the nuclear
      membrane-pore complex that is found in actively proliferating cells such as germ
      and some neoplastic cells. AL are suspected to be involved in the deposition or
      processing of mRNA: The enhanced coexpression of AL and mRNAs of three tyrosine
      kinase-containing receptors in RVH-6849 cells may represent such a relationship.

PMID- 1354403
TI  - Proceedings of the 29th Scandinavian Congress of Neurology. Aarhus, Denmark, June
      17-20, 1992. Abstracts.

PMID- 1354402
TI  - The origin of brainstem noradrenergic and serotonergic projections to the spinal
      cord dorsal horn in the rat.
AB  - Although it has been proposed that the locus coeruleus is the predominant, if not
      exclusive, brainstem origin of the noradrenergic innervation of the spinal dorsal
      horn, pharmacological studies argue otherwise. In this study we made localized
      injections of the retrograde tracer wheatgerm agglutinin conjugated to apo
      horseradish peroxidase gold (WGA:apoHRP-Au), in conjunction with
      immunocytochemical labeling for tyrosine hydroxylase (TH) or serotonin (5-HT), to
      identify the brainstem source of the noradrenaline (NA) and 5-HT innervation of
      the dorsal horn of the rat. Our studies were concentrated in the C5 spinal
      segment. The pattern of labeling was only studied in animals in which the tracer
      injection was restricted to the dorsal horn. In these rats, TH-immunoreactive
      neurons in widespread regions of the brainstem, including the locus coeruleus,
      subcoeruleus, A5, and A7 cell groups, were found to project to the dorsal horn.
      In terms of absolute numbers of double-labeled cells, no one noradrenergic cell
      group predominated. As expected, dorsal-horn-projecting 5-HT-immunoreactive
      neurons were found within the 5-HT populations of the rostroventromedial medulla
      and caudal pons, including the nucleus raphe magnus, nucleus
      paragigantocellularis (PGi), and ventral portions of the nucleus
      gigantocellularis (Gi). The majority of retrogradely labeled 5-HT-immunoreactive
      cells were, however, located off the midline, in the ipsilateral PGi and ventral
      Gi. Finally, a large number of retrogradely labeled, non-5-HT cells were found
      intermingled among the 5-HT cells of this region. Our results provide evidence
      that the noradrenergic regulation of nociceptive transmission at the spinal cord
      level arises from direct spinal projections of several brainstem noradrenergic
      cell groups.

PMID- 1354404
TI  - Ovarian cancer, a prevailing challenge. Proceedings of a nordic symposium.
      Stenungsbaden, May 10-11, 1991.

PMID- 1354405
TI  - Role of chemotherapy in the future treatment of ovarian cancer.
AB  - Platinum-based chemotherapy has led to an improvement in complete response rates
      and duration of median remission, but has only given a modest improvement in
      overall survival in patients with advanced ovarian cancer. Chemotherapy will in
      the future focus upon: (1) improving the complete remission rate with new
      induction regimens; (2) identifying strategies capable of converting partial
      remission into complete remission; (3) preventing or delaying recurrences in
      patients who do achieve a complete remission; (4) identifying mechanisms of
      antineoplastic drug resistance and pharmacologic techniques capable of reversing
      drug resistance. Among the treatment approaches being utilized are high-dose
      chemotherapy with autologous bone marrow transplantation, development of new
      chemotherapeutic regimens which include Taxol and hexamethylmelamine, and
      intraperitoneal chemotherapy. In addition, our understanding of the mechanisms of
      antineoplastic drug resistance has led to the development of novel therapeutic
      approaches. It has been demonstrated that resistance to platinum and alkylating
      agents is associated with both increased concentrations of cellular glutathione
      (GSH) as well as an increased capacity of tumor cells to repair damage to DNA.
      Inhibition of GSH biosynthesis with buthionine sulfoximine (BSO), a synthetic
      inhibitor of the enzyme gamma glutamyl cysteine synthetase, has led to the
      potentiation of alkylating agent activity in vitro and in vivo. A phase I trial
      of BSO plus melphalan is currently in progress and a trial of BSO plus
      carboplatin is planned. Inhibition of the DNA repair process with aphidicolin
      potentiates the cytotoxicity of cisplatin in drug-resistant tumor cells. Clinical
      trials of aphidicolin plus cisplatin await the completion of ongoing phase I
      trials of aphidicolin.

PMID- 1354406
TI  - [Clinicopharmacology of Arduan].
AB  - The paper presents clinicopharmacological investigations of Arduan carried out in
      Hungary and in other countries. The aim of the research work is to find an ideal
      muscle relaxant without side-effects, which are mainly cardiovascular.
      Pipecuronium bromide (Arduan) is a compound with steroid structure; it has a long
      duration of action and, most importantly, it does not affect circulation. The
      properties of pipecuronium bromide will be discussed and compared to those of
      pancuronium and vecuronium bromide.

PMID- 1354407
TI  - Myocardial potassium balance associated with regional ischaemia in the pig:
      effects of beta-adrenoceptor blockade, duration of ischaemia and preceding
      ischaemic periods.
AB  - The effects of beta-adrenoceptor blockade, duration of ischaemia and preceding
      ischaemic periods on ischaemia-induced changes in myocardial K+ balance were
      studied in 12 open-chest pigs. Coronary venous blood was directed through a shunt
      from the coronary sinus to the right atrium. Continuous recordings of arterial,
      shunt blood [K+] and shunt flow enabled us to compute myocardial K+ balance
      during and after consecutive 2-, 2-, 5-, 10- and 2-min periods of regional
      ischaemia separated by 30 min of reperfusion. beta-adrenoceptor blockade
      (propranolol 1 mg kg-1 i.v.) given between the first and second ischaemic period
      did not alter the effects of 2 min ischaemia on myocardial K+ balance. Total K+
      losses induced by 2, 5 and 10 min of ischaemia were 67.1 (40.6-93.3), 106.7 (69.4
      176.8) and 192.2 (117.7-332.6) mumol 100 g-1, respectively. Thus, the plateau
      observed in extracellular [K+] between 2 and 10 min of regional ischaemia could,
      at least partly, be explained by continuous drainage of K+ from ischaemic
      myocardium into the surrounding normally perfused tissue. The total K+ loss
      induced by the second and last 2-min ischaemic period were 67.1 (40.6-93.3) and
      35.6 (23.1-53.6) mumol 100 g-1 (P less than 0.001), respectively. This reduction
      shows that ion homeostasis during ischaemia was greatly changed in myocardium
      which had been 'preconditioned' and 'stunned' by 5 plus 10 min of ischaemia.
      Total amount, maximal rate and duration of post-ischaemic K+ reuptake increased
      with the duration of the preceding ischaemia. Moreover, K+ re-uptake after 2 min
      of ischaemia and the number of sarcolemmal Na/K pumps ([3H]ouabain binding), were
      normal in stunned myocardium. From these observations we conclude that
      progressive stimulation of the Na/K-pump occurred when ischaemia was prolonged
      from 2 to 10 min, and that Na/K-pump function was preserved in stunned
      myocardium.

PMID- 1354408
TI  - Establishment and characterization of an etoposide-resistant human small cell
      lung cancer cell line.
AB  - An etoposide-resistant subline, SBC-3/ETP, from a human small cell lung cancer
      cell line, SBC-3, was developed by continuous exposure to increasing
      concentrations of etoposide in culture. The SBC-3/ETP was 52.1-fold more
      resistant to etoposide than the parent cell line. The SBC-3/ETP was highly cross
      resistant to teniposide, adriamycin, vinca alkaloids, 4
      hydroperoxycyclophosphamide, CPT-11 and mitomycin C, and marginally cross
      resistant to cisplatin, while the subline showed a collateral sensitivity to
      bleomycin. Topoisomerase I activity in the SBC-3/ETP was reduced to an extent of
      one half and topoisomerase II activity to an extent of one eighth in comparison
      with those of the SBC-3. Intracellular accumulation of [3H]-etoposide in the SBC
      3/ETP was significantly lower in comparison to the SBC-3. An overexpression of
      MDR1 mRNA, and the presence of its product, P-glycoprotein, were detected in the
      SBC-3/ETP by Northern blotting and flowcytometry using a monoclonal antibody of
      the protein, MRK16. These results indicate that a decreased activity of
      topoisomerase II is the major factor for the development of etoposide resistance,
      and that an overexpression of the MDR1 gene is responsible, in part, for the
      development of resistance to the drug and some structurally unrelated compounds
      such as adriamycin and vinca alkaloids.

PMID- 1354410
TI  - 9th European Congress of Neurosurgery. Moscow, June 23-29, 1991.

PMID- 1354409
TI  - Hormonal profiles in Italian late-onset adrenal hyperplasia correlate with HLA
      class III polymorphisms.
AB  - To investigate the genetic polymorphisms of the HLA region in late-onset adrenal
      hyperplasia, 13 Italian patients affected by the disease were analyzed for: (1)
      HLA-A and -B typing; (2) restriction fragment length polymorphism (RFLP) of DR
      beta, DQ beta, DQ alpha, 21-hydroxylase A and B genes; (3) fourth complement
      fraction loci A and B (C4A and C4B), second complement fraction (C2) and
      properdin B factor (Bf) complement typing; (4) hormonal characteristics
      associated with some HLA haplotypes. HLA alleles B14 and DR beta 1 were found to
      be significantly more frequent in patients with respect to controls (relative
      risk: 8.7 and 7.2, p less than 0.001 and p less than 0.0001, respectively). Also
      C4B*2, 1 duplication was more frequent in patients than in normal subjects (23%
      vs. 1.5%, p less than 0.0001). Moreover, patients carrying a duplicated C4B (as
      well as those having the B14 antigen) showed higher 17-hydroxyprogesterone levels
      after ACTH stimulation. RFLP analysis of 21-hydroxylase genes with a specific
      probe revealed a duplication of 21-hydroxylase A gene in 40% of patients. All
      these individuals carried the C4A*2 B*2,1 phenotype and 75% of them displayed a
      clearly recognizable duplication at the C4B locus. These data support the
      hypothesis that in late-onset adrenal hyperplasia the 21-hydroxylase A
      pseudogene, even if inactive, may play a negative role in the regulation of 21
      hydroxylase biosynthesis. Furthermore, we suggest analyzing class III phenotypes
      to screen the enzymatic defect.

PMID- 1354411
TI  - [Effect of 8-hydroxycarteolol in normal human eyes].
AB  - The authors studied the ocular hypotensive effect of 8-hydroxycarteolol, a main
      metabolite of carteolol in normal human eyes, after topical administration in a
      double masked randomized study. After instillation of 0.01%, 0.1%, 0.5% and 1%
      ophthalmic solutions of 8-hydroxycarteolol, statistically significant reduction
      of intraocular pressure was observed 8 and 24 hours after administration (p less
      than 0.05). It's maximum reduction of intraocular pressure, 1.6 +/- 0.5 mmHg was
      produced 24 hours after treatment by 0.1% solution. However, diurnal variation of
      IOP did not show a statistically significant difference.

PMID- 1354412
TI  - Phorbol ester-induced hairy cell features on chronic lymphocytic leukemia cells
      in vitro.
AB  - Leukemic cells from eight patients with chronic lymphocytic leukemia were
      isolated and cultured in the continuous presence of 12-O-tetradecanoylphorbol 13
      acetate (TPA) at a concentration of 1.6 x 10(-9) M for 4-10 days. Aliquots of
      cells were then analyzed at intervals of 24-72 hr for changes in morphology, acid
      phosphatase staining (AP), and expression of two hairy cell-associated surface
      antigens, HCL1 (CD22, Leu 14) and HCL3 (CD11c, Leu M5). All cases studied showed
      typical B-CLL phenotype, and only a small proportion of cells expressed CD22 and
      CD11c (mean 7% and 4.9%, respectively). TPA treatment induced the coexpression of
      CD22 (mean 49%) and CD11c (mean 48%) and tartrate-resistant acid phosphatase in
      seven of eight cases. Morphologically, cells in TPA cultures expressed hairy cell
      features that were evident in light and electron microscopic studies.
      Collectively these changes indicate that TPA can induce hairy cell features on
      CLL cells in vitro, suggesting the later maturational stage of HCL compared with
      CLL.

PMID- 1354413
TI  - Tardive dyskinesia in elderly psychiatric patients: a 5-year study.
AB  - OBJECTIVE: The authors investigated the prevalence of tardive dyskinesia among
      elderly psychiatric patients who had never received neuroleptic medication before
      their first hospitalization. METHOD: The study was performed in the geriatric
      psychiatry unit of a university-affiliated hospital in Canada and involved all
      first-admission patients admitted from September 1984 through August 1989 who had
      never taken neuroleptic drugs. In September and October 1989, the patients who
      were available for follow-up were examined and given ratings on the Abnormal
      Involuntary Movement Scale to establish the presence or absence of tardive
      dyskinesia. The patients' records were reviewed for information on age,
      diagnosis, duration of hospitalization, neuroleptic treatment received after
      admission, anticholinergic drugs received, and drug-free periods. RESULTS: Of the
      162 patients who were available and whose data were analyzed, a total of 99 had
      been treated with neuroleptics, and 35 (35.4%) of these were found to have
      tardive dyskinesia. Two of the 35 also had tardive dystonia. Significantly more
      patients with major depression than patients with primary degenerative dementia
      or delusional psychosis had tardive dyskinesia. CONCLUSIONS: This study confirms
      the higher vulnerability of elderly psychiatric patients treated with
      neuroleptics to the development of tardive dyskinesia. The authors stress that
      caution is especially necessary when neuroleptics are prescribed for older
      patients with major affective disorders.

PMID- 1354414
TI  - Vector density gradients and the epidemiology of urban malaria in Dakar, Senegal.
AB  - The dispersion of anopheline mosquitoes from their breeding places and its impact
      on malaria epidemiology has been investigated in Dakar, Senegal, where malaria is
      hypoendemic and almost exclusively transmitted by Anopheles arabiensis. Pyrethrum
      spray collections were carried out along a 910-meter area starting from a
      district bordering on a permanent marsh and continuing into the center of the
      city. According to the distance from the marsh, vector density (the number of An.
      arabiensis per 100 rooms) at 0-160, 160-285, 285-410, 410-535, 535-660, 660-785,
      and 785-910 meters was 84, 40, 5, 2, 2, 0.4, and 0, respectively, during the dry
      season, and 414, 229, 110, 84, 99, 69, and 21, respectively, during the rainy
      season. The proportion of 8-11-year-old children with negative immunofluorescent
      antibody test results for Plasmodium falciparum was 17%, 28%, 44%, 54%, 50%, 63%,
      and 73%, respectively, in these different sections. Malaria prevalence in the
      community was maximum in the area bordering on the marsh where it ranged from 1%
      to 15% (average 6%) according to age and season of the year. These findings show
      the epidemiologic importance of vector density gradients in Dakar. The
      implications for malaria control in urban areas are discussed.

PMID- 1354415
TI  - Molecular characterization of Mexican stocks of Trypanosoma cruzi using total
      DNA.
AB  - Seventeen Mexican Trypanosoma cruzi stocks and five South American reference
      strains were analyzed by Hind III restriction fragment length polymorphisms
      associated with ribosomal RNA gene spacers and by HinfI digestion patterns of
      total DNA. Our findings demonstrate the occurrence of genetic heterogeneity
      within these stocks. Hierarchic and non-hierarchic clustering of these molecular
      characters allowed the formation of groups that correlate with the geographic
      origin of the stocks. The HinfI digestion pattern permitted the identification of
      DNA fragments from the kinetoplast maxi-circles, and therefore represents a
      simple and convenient method for conducting epidemiologic surveys in laboratories
      in developing countries.

PMID- 1354416
TI  - Grouping of hantaviruses by small (S) genome segment polymerase chain reaction
      and amplification of viral RNA from wild-caught rats.
AB  - A single pair of consensus primers in the polymerase chain reaction (PCR)
      amplified a conserved region of the small genome segment of twenty hantavirus
      isolates. Isolates tested included representatives of the four recognized
      hantaviruses, Hantaan, Seoul, Puumala and Prospect Hill, as well as isolates from
      Mus musculus (Leakey), Bandicota indica (Thailand 749), and Suncus murinus
      (Thottapalayam). Viruses from the Nairovirus and Phlebovirus genera yielded
      negative results. The amplification products were 281-nucleotide pairs (np) in
      length, with the exception of Thottapalayam, which had an amplification product
      of approximately 320 np. Products of all isolates were detected by Southern
      hybridization with a 32P-labeled Hantaan 76-118 amplicon, while an
      oligonucleotide probe to a conserved region of the amplified fragment failed to
      detect some isolates of Seoul and Puumala viruses. Restriction endonuclease
      analysis allowed three groupings: Hantaan-like viruses, Seoul-like viruses, and a
      diverse group of patterns for the other viruses. Differences were found within
      the Seoul-like virus group by this method, whereas the Hantaan-like viruses were
      shown to be similar. RNA extracted from tissues of seropositive and seronegative
      rats trapped in Baltimore showed the practical application of the test.
      Hantavirus-specific RNA was detected in 12 (92%) of 13 seropositive rats, but not
      in seronegative rats. This simple method for detecting and characterizing
      hantaviruses has potential for epidemiologic studies and for diagnosing human
      hantavirus infections.

PMID- 1354417
TI  - Dendrocyte population in cutaneous and extracutaneous Kaposi's sarcoma.
AB  - In order to investigate the hypothesis that the spindle cells of Kaposi's sarcoma
      originate from dendrocytes, we stained 22 cases of cutaneous and extracutaneous
      Kaposi's sarcoma for the presence of factor XIIIa. We selected eight lesions from
      the skin, five from the oral mucosa, four from gastrointestinal mucosa, three
      from lymph nodes, and one each from esophagus and conjunctiva for this study. The
      majority of cutaneous and lymph node Kaposi's sarcoma lesions had a considerable
      number of dendrocytes admixed with the spindle tumor cells. Of the five oral
      mucosal lesions only three showed a focal presence of dendrocytes. No dendrocytes
      were observed in the lesions biopsied from the gastrointestinal mucosa,
      esophagus, and conjunctiva. Our findings suggest that the proliferation of
      dendrocytes seen within the lesions of Kaposi's sarcoma in the skin and lymph
      nodes probably represents a nonspecific host response in organs where they are
      normally present, and it is unlikely that they constitute the neoplastic cells of
      Kaposi's sarcoma.

PMID- 1354418
TI  - Multinucleate cell angiohistiocytoma.
AB  - We report a case of multinucleate cell angiohistiocytoma occurring in a 50-year
      old woman and presenting with a 4-year history of asymptomatic red papules on the
      face. Histologically, there was a dermal vascular proliferation associated with
      numerous multinucleate cells. Immunohistochemical studies showed vascular spaces
      surrounded with mature vascular endothelial cells, and the presence of numerous
      interstitial factor XIIIa+ cells. Multinucleate cells exhibited intermediate
      filaments of the vimentin type, but were not stained by endothelial cell or
      macrophage markers, and were factor XIIIa-. This condition must be addressed in
      the differential diagnosis of other skin vascular proliferations, such as
      Kaposi's sarcoma and angiofibromas.

PMID- 1354419
TI  - FMRFamide-like immunoreactivity in the brain and pituitary of the goldfish,
      Carassius auratus.
AB  - The distribution of FMRFamide-like immunoreactivity was determined in the brain
      and the pituitary of the goldfish, Carassius auratus. Immunoreactive perikarya
      were observed in the olfactory nerve, nucleus entopeduncularis, nucleus
      anterioris periventricularis, nucleus posterioris periventricularis, lateral part
      of the nucleus lateralis tuberis pars posterioris, midbrain tegmentum, and
      medulla oblongata. Immunoreactive fibers were widely distributed in the brain, in
      particular in the ventral telencephalon and the hypothalamus. A few
      immunoreactive nerve fibers were observed in the pituitary. The findings are
      discussed in relation to male sexual behavior and the involvement of FMRFamide
      like peptide in pituitary functions in the goldfish.

PMID- 1354420
TI  - Multiple restriction fragment length polymorphisms in the porcine calcium release
      channel gene (CRC): assignment to the halothane (HAL) linkage group.
AB  - Two cDNA probes for the porcine calcium release channel gene (CRC) were used in
      restriction fragment length polymorphism (RFLP) analysis in an attempt to develop
      genetic markers linked to the malignant hyperthermia (stress susceptibility) gene
      (HAL). Three TaqI RFLPs, denoted CRC1-CRC3, each composed of two alleles, were
      detected. RFLPs were also detected with MspI and PvuII, but the MspI RFLP
      correlated completely with CRC3 in this material and the PvuII RFLP could not be
      scored reliably due to a minute size difference between the two allelic
      fragments. The autosomal codominant inheritance of these RFLP loci was confirmed
      by family analyses. Significant evidence for genetic linkage between the
      CRC1/CRC3 loci and the A1BG locus in the HAL linkage group confirmed a previous
      assignment of the CRC gene to chromosome 6 in the pig.

PMID- 1354421
TI  - An Eco RI restriction fragment length polymorphism at the bovine HEXB locus.

PMID- 1354422
TI  - Restriction fragment polymorphisms at the chicken anion transporter (band 3)
      locus.

PMID- 1354423
TI  - Restriction fragment length polymorphism analysis of major histocompatibility
      complex class IV (B-G) genotypes in meat-type chickens.
AB  - Restriction fragment length polymorphism (RFLP) was used as a molecular
      genotyping approach to characterize differences in major histocompatibility
      complex class IV genes in meat-type chickens. A high level of polymorphism was
      observed following digestion with each of the two restriction endonucleases PvuII
      and BglII. Examination of DNA from 54 chickens revealed 23 polymorphic fragments.
      Application of RFLP techniques in the analysis of family groups should make
      possible the determination of B-G genotypes in the meat type chickens.

PMID- 1354424
TI  - [Results of a survey carried out on postgraduate training during MAPAR 1991].

PMID- 1354425
TI  - Listeriosis in patients with chronic lymphocytic leukemia who were treated with
      fludarabine and prednisone.
AB  - OBJECTIVE: To determine whether therapy with fludarabine plus prednisone in
      patients with chronic lymphocytic leukemia increases the risk for developing
      listeriosis. DESIGN: Retrospective cohort study based on hospital surveillance
      data. SETTING: Referral cancer center. PARTICIPANTS: A total of 795 patients with
      chronic lymphocytic leukemia who received care at The University of Texas M. D.
      Anderson Cancer Center between 1980 and 1990. INTERVENTIONS: Patients were
      treated with fludarabine alone or fludarabine and prednisone. MEASUREMENTS: The
      listeriosis attack rate was analyzed according to the type of treatment received.
      RESULTS: Seven of 408 patients in the fludarabine group developed listeriosis
      (1.7%; 95% Cl, 0.2% to 6%) compared with 0 of 387 patients who received
      conventional chemotherapy alone (0% to 0.9%; P = 0.015). The 7 patients were
      among 248 patients who were treated with both fludarabine and prednisone; none of
      160 patients treated with fludarabine alone developed listeriosis (P = 0.045 by
      the Fisher exact test). A dramatic reduction in CD4 counts occurred in patients
      after fludarabine and prednisone treatment and coincided with the development of
      listeriosis. CONCLUSION: The administration of fludarabine plus prednisone is
      associated with an increased incidence of listeriosis in patients with chronic
      lymphocytic leukemia. The depletion of CD4 cells may underlie the pathogenesis.

PMID- 1354426
TI  - Prolonged weakness after long-term infusion of vecuronium bromide.

PMID- 1354428
TI  - The proliferative fraction in lymph nodes: a comparison of proliferating cell
      nuclear antigen morphometry to flow cytometry.
AB  - A monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin) has
      recently become available. This antibody, as opposed to Ki-67, can be used on
      formalin-fixed, paraffin embedded tissue sections and allows retrospective
      comparison of PCNA positivity to percent S + G2 + M of the cell cycle. To compare
      fresh lymphoma deoxyribonucleic acid (DNA) analysis with PCNA activity on fixed,
      paraffin-embedded sections, prospective flow cytometric studies of cell cycle
      analysis were performed on lymph nodes removed from 10 patients for diagnosis.
      Six patients had T-cell lymphoma, two had B-cell lymphoma, and two were benign.
      Using the peroxidase-antiperoxidase method, the nuclear positivity of archival
      lymphoma cases was also examined. To quantify PCNA positivity, a unique
      morphometric method was employed that utilized digital imaging by high definition
      television and ELAS (Earth Land Application Software), a geoscience software used
      extensively for color quantitation of remote sensed data. The immunologic percent
      PCNA positivity was 26.1 +/- 20 vs. percent S + G2 + M by flow cytometry of 22.4
      +/- 10 with a correlation coefficient (r) of 0.55. This r-value compared
      favorably to data generated for Ki-67 in solid malignant neoplasms. The six more
      concordant cases had a percent PCNA positivity of 26.5 +/- 10.0 and a percent S +
      G2 + M of 27.3 +/- 8.6, r = 0.96. Our study is unique in that it compared fresh
      lymphoma DNA analysis data with paraffin PCNA data. It is our conclusion that
      immunologic PCNA positivity in paraffin sections correlates with fresh flow
      cytometric S + G2 + M in lymph nodes, although careful attention must be paid to
      the area of the node quantified for PCNA.

PMID- 1354429
TI  - Mitochondrial and nuclear variants in a U.S. black population: origins of a
      hybrid population.
AB  - The maternal transmission of mitochondria in higher eukaryotes makes it possible
      to distinguish between reciprocal matings, since offspring possess the
      mitochondrial DNA variants received from the mother. This possibility can be
      extended to hybrid populations, the mitochondrial frequencies reflecting the
      relative maternal contributions from the parental populations. Nuclear variations
      reflect the relative genetic contributions of the parental populations,
      irrespective of parental sex. The U.S. Black population is a hybrid of West
      African and European populations. The African-European matings that contributed
      to the present Black population are traditionally considered to have been almost
      exclusively between African females and European males. We have studied nuclear
      and mitochondrial variants in a sample of U.S. Blacks, comparing them with
      published frequencies from African and Caucasian groups. Our results suggest that
      the mitochondria of present-day American Blacks are derived from Caucasians to an
      extent similar to nuclear genes. In contrast to traditional beliefs, the
      contribution from Caucasian females is of the same magnitude as that from
      Caucasian males.

PMID- 1354427
TI  - Cerebrospinal fluid analysis in human immunodeficiency virus infection.
AB  - Cerebrospinal fluid (CSF) analytes were evaluated in 59 human immunodeficiency
      virus (HIV+) individuals to assess neurological involvement. Glucose, total
      protein, cell counts, p24 antigen, CSF: serum albumin/IgG ratios, and oligoclonal
      bands were measured. Eighty percent of samples showed abnormalities in one or
      more analyte. In some patients samples, these abnormalities could mimic those of
      secondary opportunistic infection when none was present. The presence of
      oligoclonal banding in CSF (31 percent) and disturbances in CSF: serum
      albumin/IgG ratio (30 percent) were related to decreases in serum CD4+
      lymphocytes. Disturbances in CSF: Serum albumin/IgG ratio were also related to
      severity of non-neurological HIV disease staging. Cerebrospinal fluid oligoclonal
      bands were distinct from that found in serum in the same subjects. Since immune
      complexes between immunoglobulins and enzymes are observed in these same
      patients, these oligoclonal bands may result in artifactually elevated enzyme
      results secondary to decreased clearance leading to erroneous clinical decisions.
      There was no significant relationship between any abnormalities and the presence
      of neurologic disease as established by a wide variety of other studies. It is
      important to recognize the limits of CSF interpretation in this patient group.

PMID- 1354430
TI  - Expression of several resistance mechanisms in untreated human kidney and lung
      carcinomas.
AB  - Thirty human renal cell carcinomas and 94 non-small cell lung carcinomas of
      previously untreated patients were analyzed for the presence of P-glycoprotein,
      glutathione S-transferase-pi and topoisomerase II by means of
      immunohistochemistry. In the renal cell carcinomas investigated, two resistance
      markers were seen in 53% and three resistance markers in 36% of the cases. In
      only three tumors was one resistance mechanism observed. In the 94 non-small cell
      lung carcinomas 34% had two and 20% three resistance mechanisms, whereas 24% of
      the tumors revealed only one resistance mechanism. For determining the resistance
      of the tumors against drugs an in vitro short-term test was used. Only 12% of the
      sensitive lung tumors had more than one resistance mechanism, whereas 70% of the
      resistant tumors did. Thus a significant relationship exists between the
      resistance measured in vitro and the overexpression of P-glycoprotein or
      glutathione S-transferase-pi and the down-regulation of topoisomerase II.

PMID- 1354431
TI  - DNA synthesis enzymes and proliferating cell nuclear antigen in normal and
      neoplastic nerve cells.
AB  - The activity of nuclear DNA polymerases alpha, beta and delta/epsilon, uracil-DNA
      glycosylase, thymidine kinase and the presence of Proliferating Cell Nuclear
      Antigen (PCNA) have been examined in developing rat glial cells, in rat and human
      glioma, in human neuroblastoma and in differentiated neuroblastoma cell lines in
      vitro. During glial development the activity of all enzymes tested, except DNA
      polymerase beta, markedly decreased, suggesting their coordinate regulation in
      respect to the proliferative state of the cells. Glioma and neuroblastoma cell
      lines restore the enzymatic activities that were no longer expressed in normal
      adult cells. Neuroblastoma cell lines induced to differentiate in vitro by
      retinoic acid showed a decline of the activities of DNA polymerase alpha, DNA
      polymerase delta/epsilon, uracil-DNA glycosylase and thymidine kinase similar to
      that observed during in vivo differentiation. We also demonstrate that PCNA is
      not detectable in glial and neuronal cells at all developmental stages, but can
      be found in tumor nerve cells. A possible use of enzymatic assays or anti-PCNA
      antibodies to detect brain tumors is discussed.

PMID- 1354433
TI  - Study of immune-associated antigens (IL-1 and ICAM-1) in normal human
      keratinocytes treated by sodium lauryl sulphate.

PMID- 1354432
TI  - Pharmacokinetics of cefpodoxime proxetil and interactions with an antacid and an
      H2 receptor antagonist.
AB  - Cefpodoxime proxetil is a new oral esterified cephem antibiotic with a broad
      antibacterial spectrum. The dissolution of cefpodoxime proxetil is pH dependent.
      The objectives of this study were to characterize the pharmacokinetics of
      cefpodoxime proxetil in two different oral doses and to examine possible
      interactions with an antacid, aluminum magnesium hydroxide (Maalox 70), and an H2
      receptor antagonist, famotidine. Two studies involving the same 10 healthy
      volunteers were performed. In the first study, cefpodoxime proxetil was
      administered in two doses, 0.1 and 0.2 g. In the second study, two interventions
      were performed in a randomized crossover design. For one intervention, the
      volunteers were pretreated with 40 mg of famotidine 1 h before 0.2 g of
      cefpodoxime proxetil was administered. In the second trial, participants were
      given 10 ml of Maalox 70 2 h and 10 ml of Maalox 70 15 min before they received
      0.2 g of cefpodoxime proxetil. Serum and urine concentrations were determined by
      high-performance liquid chromatography. For the statistical evaluation, these
      data were tested by using the pharmacokinetics of 0.2 g of cefpodoxime proxetil
      from the first study. The maximum concentrations were 1.19 +/- 0.32 mg/liter
      after 0.1 g of cefpodoxime proxetil and 2.54 +/- 0.64 mg/liter after 0.2 g of
      cefpodoxime proxetil. The elimination half-lives were 149 min for 0.1 g and 172
      min for 0.2 g of cefpodoxime proxetil. The total increase in the area under the
      concentration-time curve (AUC) was dose dependent. Combination with Maalox 70
      caused a reduction in the AUC from 14.0 +/- 3.9 to 8.44 +/- 1.85 mg.h/liter.
      After famotidine, the AUC decreased to 8.36 +/- 2.0 mg . h/liter. Corresponding
      changes were registered for the maximum concentration of drug in serum, 24-h
      urine recovery, and the time to maximum concentration of drug serum. Cefpodoxime
      proxetil was well tolerated without any seriously adverse drug reactions.

PMID- 1354434
TI  - Pregnancy in aplastic anemia treated with fetal liver and bone marrow hemopoietic
      cells and antithymocyte globulin.
AB  - This report describes a patient who had severe refractory anemia and
      thrombocytopenia during her first pregnancy. She had a remission after delivery
      but two years later aplastic anemia refractory to steroid and splenectomy
      developed. After treatment with steroids and antithymocyte globulin the patient
      had repeated infusions of hemopoietic cells derived from fetal liver and bone
      marrow, leading to a 7-year remission during which time she had a further
      successful pregnancy. The patient had a relapse one year later.

PMID- 1354435
TI  - The advantages of pylorus-preserving pancreatoduodenectomy in malignant disease
      of the pancreas and periampullary region.
AB  - The aim of this study was to establish whether the pylorus-preserving
      pancreatoduodenectomy (PPPD) is a safe and radical procedure in malignant disease
      of the head of the pancreas and periampullary region, without increased morbidity
      and mortality rates compared with the standard Whipple's procedure. During the
      period 1984 to 1990, a Whipple's procedure (n = 44) or PPPD (n = 47) was
      performed in 91 patient. In-hospital mortality rates were 2% after PPPD and 5%
      after Whipple's procedure. Median duration of the resection procedure and median
      blood loss in the PPPD group were 210 minutes and 1800 mL, respectively. After
      Whipple's procedure, these figures were 255 minutes and 2500 mL, both
      significantly different (p less than 0.01) as compared with PPPD. No difference
      was found during follow-up with respect to days of gastric suctioning, start of
      liquid diet, normal diet, complaints of ulcer disease, postoperative
      complications, recurrence of disease, and survival. In all patients, curative
      resection was performed with comparable TNM (tumor, nodes, metastases) staging.
      The number of tumor-containing duodenal or gastric resection margins did not
      differ in both groups of patients (two patients after PPPD, two patients after
      Whipple's procedure). Hospital stay was significantly (p = 0.02) shorter after
      PPPD; median 14 days, compared with median 18 days after Whipple's procedure. The
      advantage of the PPPD is that it is an easier and less time-consuming operation,
      with less blood loss, a shorter hospital stay, and better weight gain (p = 0.02)
      during follow-up. In conclusion, PPPD is a safe and radical procedure for cancer
      in the head of the pancreas or periampullary region, with the same survival and
      appearance of locoregional recurrence and distant metastases as after standard
      Whipple's resection.

PMID- 1354436
TI  - The vertebrate limb: a model system to study the Hox/HOM gene network during
      development and evolution.
AB  - The potential of the vertebrate limb as a model system to study developmental
      mechanisms is particularly well illustrated by the analysis of the Hox gene
      network. These genes are probably involved in the establishment of patterns
      encoding positional information. Their functional organisation during both limb
      and trunk development are very similar and seem to involve the progressive
      activation in time, along the chromosome, of a battery of genes whose products
      could differentially instruct those cells where they are expressed. This process
      may be common to all organisms that develop according to an anterior-posterior
      morphogenetic progression. The possible linkage of this system to a particular
      mechanism of segmentation as well as its phylogenetic implications are discussed.

PMID- 1354437
TI  - A new restriction fragment length polymorphism of the ceruloplasmin gene in rat.
AB  - Using a cDNA probe of the ceruloplasmin (CP) gene, a new restriction fragment
      length polymorphism (RFLP) was detected in inbred strains of rat with the
      restriction enzyme KpnI. The RFLP behaved as a codominant trait on a single
      autosomal locus. Two alleles of the CP gene, which were tentatively designated as
      CP-A and CP-B, were almost equally distributed in 10 inbred strains. These
      indicate that the RFLP of the CP gene is a useful marker locus of the rat. We
      utilized this CP gene polymorphism for the investigation of the pathogenesis of
      the aberrant hepatic copper metabolism in LEC mutant rat, since CP has a pivotal
      role in copper metabolism in the liver. Using backcross progenies originating
      from LEC and BN rats, we found that the CP gene is not associated with the excess
      hepatic copper accumulation and the deficiency in serum CP activity, both of
      which are congenital abnormal phenotypes exhibited in LEC mutant rat.

PMID- 1354438
TI  - Amino acid transport in multidrug-resistant Chinese hamster ovary cells.
AB  - In the process of assessing the effect of anthracycline drugs on cellular
      membrane function in cultured multidrug resistant (MDR) and its parental cells,
      experiments were undertaken to investigate the kinetics of neutral amino acid
      membrane transport (the sodium dependent A and ASC systems). P-glycoprotein, a
      high molecular weight energy requiring integral membrane protein responsible for
      actively pumping drugs out of cells, has been shown to be overexpressed in MDR
      cells. It was our hypothesis that its presence might affect other membrane energy
      requiring systems such as amino acid transport. On establishing the
      concentrations of P-glycoprotein by western blotting in the two cell lines to be
      studied, the kinetics of membrane transport of the neutral amino acids alpha
      aminoisobutyric acid (AIB) and serine (SER) were investigated using the CHRC5
      multidrug resistant and AUX B1 parental Chinese hamster ovary (CHO) cells. In
      CHRC5 cells, the amount and rate (Vmax) of accumulated amino acids, was
      significantly depressed when compared to AUX B1 cells, however, there was no
      difference in the rates of amino acid efflux between these two cell lines. Using
      1,6-diphenyl 1,3,5-hexatriene (DPH) polarization to evaluate the state of
      membrane fluidity in the two cell lines studied, it was seen that CHRC5 cells
      showed a slightly lower degree of polarization than that observed in AUX B1
      cells. These results suggest, that the P-glycoprotein does not alter amino acid
      transport directly but may modify the activity or numbers of functional transport
      carriers.

PMID- 1354439
TI  - Synthesis of a 11-deoxyprostanoid in the area of preclavulones: (+-)-8,12-trans
      (5Z-14Z)-9-oxo-prosta-5,14-dienoic acid from 2-allyl-2-cyclopenten-1-one.
AB  - Following our research on the arachidonic acid metabolites and their derivatives
      with potential biological activity, we describe the synthesis of the (+-)-8,12
      trans-(5Z, 14Z)-9-oxo-prosta-5,14-dienoic acid, a 11-deoxyprostanoid correlated
      to the class of Preclavulones, one of the unusual families of marine eicosanoids
      from the coral Clavularia Viridis with considerable biological interest.

PMID- 1354440
TI  - Congress of the German Society of Hygiene and Microbiology. Munster, September 30
      October 2, 1991. Abstracts.

PMID- 1354441
TI  - 2nd Congress on Immunointervention in Autoimmune Disease. Paris, 13-16, 1991.

PMID- 1354443
TI  - Selective impairment of long-term but not short-term conditional fear by the N
      methyl-D-aspartate antagonist APV.
AB  - Previous research has indicated that the competitive N-methyl-D-aspartate (NMDA)
      antagonist APV (DL-2-amino-5-phosphonovalerate) prevents the Pavlovian
      conditioning of fear to contextual stimuli when tested 24 hr, but not
      immediately, after training. The present study investigated this differential
      time-dependent effect of APV on fear conditioning. Rats were given either APV or
      saline and presented with 3 footshocks in a distinctive chamber. Promptly after
      the shock, rats that had received APV exhibited a species-typical fear response
      freezing. However, the freezing lasted for only a short period of time (less than
      3 min) compared with that of controls. An immediate-shock procedure showed that
      freezing was entirely a conditional response to the chamber. In addition, the
      results of a savings test suggest that APV impairs storage rather than retrieval
      processes. These results indicate that there are two temporally distinct
      associative fear processes, a short-term NMDA-independent conditional fear and a
      long-term NMDA-dependent conditional fear.

PMID- 1354442
TI  - Additive effects of c-erbB-2, c-Ha-ras, and transforming growth factor-alpha
      genes on in vitro transformation of human mammary epithelial cells.
AB  - MCF-10A cells are a spontaneously immortalized untransformed human mammary
      epithelial cell line. We have previously shown that overexpression of a human
      point-mutated c-Ha-ras proto-oncogene, the rat c-neu (c-erbB-2) proto-oncogene,
      or the human transforming growth factor-alpha (TGF-alpha) gene in MCF-10A cells
      leads to in vitro transformation of such cells. To ascertain whether the
      introduction of two of these genes into MCF-10A human mammary epithelial cells
      induces a completely tumorigenic phenotype, we infected MCF-10A Ha-ras and MCF
      10A TGF-alpha cells with a recombinant retroviral vector containing the human c
      erbB-2 proto-oncogene and the hygromycin-resistance gene. Ten MCF-10A TGF-alpha/c
      erbB-2 (MCF-10A TE) and 10 MCF-10A Ha-ras/c-erbB-2 (MCF-10A HE) hygromycin
      resistant clones were randomly selected and expanded into cell lines. MCF-10A TE
      and MCF-10A HE clones expressed a 10-fold to 40-fold increase in p185 erbB-2
      protein levels compared with parental uninfected cells. These cells exhibited a
      fourfold increase in their growth rate in serum-free medium and showed a strongly
      reduced mitogenic response to exogenous epidermal growth factor or TGF-alpha
      compared with MCF-10A cells. Moreover, both MCF-10A TE and MCF-10A HE clones
      exhibited a fivefold to 20-fold higher cloning efficiency in soft agar than MCF
      10A Ha-ras, MCF-10A c-erbB-2, or MCF-10A TGF-alpha clones. However, neither MCF
      10A TE nor MCF-10A HE cells were able to grow as tumors in vivo when they were
      injected into nude mice. These results suggest that c-Ha-ras, c-erbB-2, and TGF
      alpha genes have an additive effect on the in vitro transformation of an
      immortalized human mammary epithelial cell line, but that additional genetic
      changes such as activation of other proto-oncogenes or inactivation of a tumor
      suppressor gene may be necessary to elicit a fully tumorigenic phenotype.

PMID- 1354444
TI  - Delayed-nonmatching-to-sample performance is impaired by extensive, but not by
      limited, lesions of the thalamus in the rat.
AB  - Two experiments were conducted to determine whether lesions affecting limited
      areas of the thalamus can impair the performance of rats on a spatial delayed
      nonmatching-to-sample (DNMTS) task trained before surgery. In Experiment 1, DNMTS
      was not affected by lesions produced by injecting 5 microliters of 1 mM N-methyl
      D-aspartate into either the midline thalamus (n = 16) or bilaterally 1.0 mm from
      the midline (n = 16). In experiment 2, radio-frequency lesions were made 1.0 mm
      lateral to the midline at 3 anterior-posterior locations that destroyed the full
      rostral-caudal extent of the lateral internal medullary lamina (L-IML; n = 8), or
      at single anterior-posterior locations that destroyed either the anterior (n = 8)
      or posterior (n = 8) portions of the L-IML site. Although complete L-IML lesions
      disrupted DNMTS performance to an extent comparable to that of another study
      (Mair & Lacourse, 1992), lesions that were restricted to either the anterior or
      posterior portion of the L-IML site had no significant effect on this task.

PMID- 1354446
TI  - Equivalent recognition of HIV proteins, Env, Gag and Pol, by CD4+ and CD8+
      cytotoxic T-lymphocytes.
AB  - OBJECTIVES: Cytotoxic T-lymphocytes (CTL) appear to be an important defense
      mechanism against HIV infection. This study proposes to examine the major
      histocompatibility complex (MHC)-restricted HIV-1 Env-, Gag- and Pol-specific CTL
      activities in HIV-infected asymptomatic patients. DESIGN: CD4+ and CD8+ CTL were
      examined to establish whether the same HIV-1 protein (Env, Gag or Pol) was
      recognized by both CD4+ and CD8+ CTL with MHC antigen restriction. METHODS:
      Peripheral blood mononuclear cells, CD4+ and CD8+ T-cells from 17 HIV-infected
      asymptomatic patients and 10 HIV-seronegative individuals were examined for HIV-1
      Env-, Gag- and Pol-specific MHC-restricted cytotoxicity using autologous and
      heterologous B-lymphoblastoid cell lines infected with vaccinia recombinant
      expressing HIV-1 Env, Gag and Pol proteins as targets. RESULTS: CD4+ and CD8+ CTL
      specific for the HIV-1 Env, Gag and Pol were demonstrated in the peripheral
      blood. DR4 and DQw2 were possible sites of MHC class II restriction of CD4+ CTL.
      Possible MHC class I restriction sites of CD8+ CTL included A2 and B8 for Env, A1
      and A2 for Gag, and A2 and B8 for Pol antigen. CONCLUSIONS: These observations
      should help to define more precisely the nature and elements of protective
      immunity and to evaluate AIDS vaccine strategies.

PMID- 1354447
TI  - Biphasic rate of CD4+ cell count decline during progression to AIDS correlates
      with HIV-1 phenotype.
AB  - OBJECTIVE: To determine the kinetics of decline of CD4+ lymphocytes in HIV-1
      infected asymptomatic homosexual men. METHODS: CD4+ lymphocytes were enumerated
      in a cohort of 187 HIV-1-infected initially asymptomatic homosexual men seen at 3
      month intervals over 5 years. During follow-up, 45 men progressed to AIDS
      (excluding cases presenting with Kaposi's sarcoma). Correlation between rate of
      CD4+ cell decline and presence of a particular HIV-1 biological phenotype was
      analysed in 43 participants. RESULTS: CD4+ cell counts declined slowly and
      continuously in HIV-1-seropositive men who remained asymptomatic during follow
      up. A biphasic CD4+ cell count decline was observed in the group who developed
      AIDS: the decline was slow and steady (5.6 x 10(6)/l per month, similar to that
      observed in the asymptomatic group) until 18 months before AIDS diagnosis, but
      became three to five times faster thereafter. Rapid CD4+ cell decline was
      significantly related to syncytium-inducing, fast-replicating HIV-1 isolates;
      during the period of slow and steady CD4+ cell count decline, non-syncytium
      inducing isolates were predominant. CONCLUSIONS: At an average of 18 months
      preceding AIDS diagnosis, a three to fivefold increase in the rate of loss of
      CD4+ lymphocytes occurs, and may be related to the appearance of a more virulent
      HIV-1 phenotype.

PMID- 1354445
TI  - Adverse effects of systemic opioid analgesics.
AB  - Adverse effects of opioids are multiple. They are most often receptor-mediated
      and inseparable from their desired effects. The most severe mishaps with opioids
      are related to their respiratory depressant effect, which is widely influenced by
      factors such as pain, previous opioid experience and awareness. Other relevant
      central nervous system effects of opioids include cough suppression, nausea and
      vomiting, rigidity, pruritus and miosis. The cardiovascular adverse effects of
      opioids are mainly related to histamine release and differ widely between
      agonists and agonist-antagonists. Gastrointestinal effects such as constipation,
      reflux and spasms of the bile duct are well described. Adverse effects on
      endocrine, immunological and haematological functions are possible, while
      allergic reactions are extremely rare. The adverse effects of long term use are
      overestimated. Systemic toxicity is negligible and development of tolerance is
      minimal while treating pain. In the clinical setting of pain control, addiction
      and withdrawal do not pose significant problems. Nevertheless, the possible
      effects of opioids on the unborn child should always be considered. Overall,
      opioids show a good record of safety. Their use should not be unduly limited by
      unfounded fears of adverse effects, but these effects should be avoided by
      anticipation and prevention.

PMID- 1354448
TI  - Clinical and laboratory predictors of survival in Gambian patients with
      symptomatic HIV-1 or HIV-2 infection.
AB  - OBJECTIVES: To determine which clinical and immunological features of patients
      with symptomatic HIV-1 and HIV-2 infection best predict survival in The Gambia.
      METHODS: All patients presenting to two hospitals in The Gambia between January
      1987 and June 1990 with symptoms or signs suggesting chronic HIV infection were
      tested for HIV-1 and HIV-2 antibodies. Eighteen HIV-1 and 31 HIV-2-infected
      patients were recruited to the study, investigated intensively on admission and
      followed up until the end of 1990. Presenting clinical features, such as
      Karnofsky score, diagnosis of AIDS according to World Health Organization Bangui
      or Centers for Disease Control criteria and number of associated infections,
      together with five immunological measurements, as well as type of HIV infection,
      were related to length of survival using proportional hazard models fitted to
      Kaplan-Meier plots of survival times. RESULTS: Karnofsky score and diagnosis of
      AIDS were the best clinical predictors of survival. Type of HIV infection or
      number of associated infections did not predict outcome. The most powerful
      laboratory predictors were log(e) serum neopterin level, CD4 cell count and
      log(e) serum beta 2-microglobulin (beta 2M) level. The estimated median survival
      times (90% confidence interval) of the HIV-1 and HIV-2-infected were six (4-11)
      and 13 (9-20) months, respectively. These survival times do not differ
      significantly. CONCLUSIONS: The Karnofsky score and measurements of serum
      neopterin or beta 2M, which are easier and cheaper to perform than CD4 counts,
      may prove to be useful guides to prognosis for HIV infection in Africa.

PMID- 1354450
TI  - Application of the World Health Organization system for HIV infection in a cohort
      of homosexual men in developing a prognostically meaningful staging system.
AB  - OBJECTIVE: Validation of a modified version of the recently proposed World Health
      Organization (WHO) staging system for HIV infection and disease in a cohort of
      homosexual men. METHODS: Five hundred and thirty HIV-positive men followed for a
      median of 51 months (range, 1-98 months) were eligible for analysis. Subjects
      were classified into stages at their first seropositive visit and at all
      subsequent visits. RESULTS: As of 1 April 1991, 136 subjects (26%) had progressed
      to stage IV of the modified WHO system on the basis of their CD4 lymphocyte
      counts, and 78 subjects (15%) had died. Kaplan-Meier estimates for progression to
      stage IV from stages I, II and III were 52.8 +/- 7.5% over 6.6 years, 58.1 +/-
      7.1% over 5.9 years and 66.5 +/- 9.7% over 5.7 years (log-rank P = 0.0001).
      Estimated median times to stage IV were 6.4, 5.3 and 3.8 years from stages I, II
      and III, respectively. Estimated median times to death were 10.9, 8.2, 6.3 and
      1.7 years from stages I to IV, respectively. Results remained unchanged when CD4
      lymphocyte count was replaced with lymphocyte count in the laboratory axis of the
      staging system. CONCLUSIONS: The proposed staging scheme, based on the WHO
      system, provides a prognostically meaningful classification for HIV infection in
      a cohort of homosexual men. Furthermore, the use of absolute lymphocyte count as
      a valid alternative for CD4 lymphocyte count has implications for the
      applicability of this system in many parts of the world where diagnostic
      resources are limited.

PMID- 1354451
TI  - CD4 lymphocyte depletion prior to the development of AIDS.

PMID- 1354449
TI  - Vapreotide, a somatostatin analogue, in cryptosporidiosis and other AIDS-related
      diarrhoeal diseases.
AB  - OBJECTIVE: To evaluate the efficacy and tolerance of vapreotide, a new
      somatostatin analogue, in the treatment of refractory AIDS-related diarrhoea.
      DESIGN: An open, non-comparative pilot trial. SETTING: The trial was conducted in
      10 medical centres in France. PATIENTS, PARTICIPANTS: Thirty-four AIDS patients
      with chronic diarrhoea unresponsive to conventional antidiarrhoeal therapy were
      enrolled. Cryptosporidiosis was diagnosed in 21 out of 30 evaluable patients.
      Mean number of stools prior to therapy was 10.1 +/- 4.9 per day (range, 3-20
      stools per day). INTERVENTION: After initial baseline studies, patients received
      subcutaneous vapreotide at escalating doses of 400 (23 patients) or 500
      micrograms (seven patients), between two and six times daily. MAIN OUTCOME
      MEASURES: Efficacy was assessed after 14 days of therapy, when it was found to be
      effective. Responders were offered the opportunity to continue receiving therapy.
      RESULTS: Four patients demonstrated a complete response and 12 a partial response
      with greater than 50% reduction in daily stool emission. Fourteen patients did
      not respond to doses up to 2400 micrograms/day. Patients with conditions other
      than cryptosporidiosis had a significantly higher probability of response (P =
      0.013), as did those with milder diarrhoea (less than 10 stools per day). Median
      duration of response was 1.5 months (range, 0.5-5 months); relapse occurred in
      five out of eight responders despite maintenance therapy. Toxicity was minimal.
      CONCLUSIONS: We conclude that AIDS patients with diarrhoea not caused by
      Cryptosporidium may benefit from vapreotide therapy.

PMID- 1354452
TI  - Oligonucleotide hybridization used to detect short non-contiguous sequences.
AB  - We describe the use of an oligonucleotide construction as a hybridization probe
      to detect short noncontiguous regions of sequence identity. Oligonucleotides
      complementary to various portions of the conserved heptamer and nonamer sequences
      flanking immunoglobulin variable region genes at the 3' end were used in this
      model system. We show that short oligonucleotides alone (7 bp or 9 bp) cannot be
      used as hybridization probes, but a construction containing both conserved
      sequences linked by a bridge will hybridize. The bridge is formed by degenerate
      bases (any base potentially at each position) and serves to maintain the spacing
      originally present between heptamer and nonamer. We show that such a bridging
      oligonucleotide probe can be used for hybridization analysis both on Southern
      blots and in bacterial screening.

PMID- 1354453
TI  - Converting restriction sites by filling in 5' extensions.

PMID- 1354454
TI  - Immunotoxic effects of MPT-IP containing 60% methylparathion in mice.
AB  - The effects of a single large and repeated small doses of MPT-IP (the industrial
      product used to produce Wofatox EC 50) containing 60% methylparathion, on the
      humoral and cellular immunoreactivity of CFLP mice were investigated.
      Administration of a single LD50/2 dose 3 d prior to immunization caused a 40%
      increase in the number of splenic PFC on the 5th day but no significant increase
      in serum antibody titre on the 7th day after immunization. Treatment for 4 weeks
      with an LD50/40 dose resulted in a 100% increase in splenic PFC, also not
      associated with a change in serum antibody titre. Under the same conditions and
      LD50/20 dose had no effect on these parameters. Neither the single large nor the
      repeated small doses had any effect on the intensity or time course of a DTH
      reaction. The results show that MPT-IP has an immunotoxic potential in mice under
      certain experimental conditions.

PMID- 1354455
TI  - Assessment of pentachlorophenol exposure in humans using the clearance concept.
AB  - 1. Pentachlorophenol (PeCP), a widely-used wood preservative, is a ubiquitous
      compound which has been found to be carcinogenic in mice. The objective of this
      study is to assess the average net daily intake of PeCP in cohorts of individuals
      who are: (1) not specifically exposed to PeCP, (2) residents of homes made of
      PeCP-treated logs and (3) occupationally exposed to PeCP. 2. The average net
      daily intake was calculated using a basic pharmacokinetic principle, the
      clearance (CL) concept: net daily intake equals CL (in 1 d-1) times the average
      steady-state concentration of PeCP in plasma (Css). Css values reported in the
      literature were used for the calculations. 3. Because the two definitive studies
      on PeCP toxicokinetics in humans have given conflicting results, kinetic
      information from human exposure to PeCP was reviewed. Plasma clearance was
      estimated from retrospective analysis of urine and plasma concentrations measured
      in people after long-term exposure to PeCP. An overall clearance of 0.425 l d-1
      was obtained. 4. In groups of individuals who are not specifically exposed to
      PeCP, net daily intake estimated in eight countries varied from 5 micrograms
      (Nigeria) to 37 micrograms (The Netherlands). Net intake was between 51
      micrograms d-1 and 157 micrograms d-1 in residents of homes made of PeCP-treated
      logs. In individuals occupationally exposed to PeCP, net daily intake varied
      widely (from 35 micrograms to about 24,000 micrograms) depending on the type of
      work.

PMID- 1354456
TI  - Dangerous mixture of household detergents in an old-style toilet: a case report
      with simulation experiments of the working environment and warning of potential
      hazard relevant to the general environment.
AB  - A housewife cleaned toilet porcelain connected directly to a sewage storage tank
      with a mixture of cleaning agents; sodium hypochlorite (NaOCl) and hydrochloric
      acid (HCl) solutions. She complained of insomnia on the night after cleaning and
      suffered from severe metabolic acidosis with extremely low blood pH, PCO2 and
      bicarbonate values. She recovered from the acidosis after bicarbonate
      transfusion, plasmapheresis and plasma exchange. Permanent blindness ensued,
      however, from the third day after the event. These clinical symptoms suggested
      that the toxic substances responsible were chloramine and methyl chloride. Their
      generation was confirmed by in-vitro experiments, mixing NaOCl, HCl and pooled
      urine from normal people. In the simulation, the methyl chloride level far
      exceeded (100,000 ppm) the maximal allowable concentration recommended (ca 400
      ppm) by the American Conference of Governmental Industrial Hygienists (ACGIH).
      Chloramine's toxic actions were confirmed using purified enzyme assay, and the
      inhibition of carbonic anhydrase and aldehyde dehydrogenase and the enhancement
      of superoxide dismutase activity were confirmed in neutral pH. The patient's
      clinical symptoms suggested that insomnia and permanent blindness seemed to be
      partly ascribable to chronic repetitive exposure to methyl chloride; catching a
      cold, drug intake and alcohol intake, in addition, precipitated the patient's
      visual loss. The possibility of this kind of intoxication with such a mixture of
      agents may lie latent in any situation where sewage or garbage are exposed to the
      open air.

PMID- 1354458
TI  - 1H-NMR spectroscopy as a means of monitoring nephrotoxicity as exemplified by
      studies with cephaloridine.
AB  - 1. Male albino rats were dosed intravenously with either 0.9% saline or
      cephaloridine in saline at doses of 650, 750 or 950 mg kg-1 d-1 for 7 d. 2. Urine
      analysis on day 3, after two doses of cephaloridine showed dose-related increases
      in glucose, total protein, N-acetyl beta-D-glucosaminidase, gamma
      glutamyltranspeptidase, alkaline phosphatase and lactate dehydrogenase. 1H-NMR
      spectroscopy showed corresponding disturbed profiles of products of intermediary
      metabolism indicative of a disruption of renal function. 3. By day 6, after five
      doses of cephaloridine, analysis by both 1H-NMR and conventional methods showed
      that all indices had returned to normal. 1H-NMR was demonstrated to provide
      useful complementary information to conventional techniques on the time course of
      the onset of the nephrotoxicity and the recovery phase, and was at least as
      sensitive as conventional urine analysis.

PMID- 1354457
TI  - Elevation of lead in human blood from its controlled ingestion in beer.
AB  - 1. Nine volunteers ingested high levels of lead in beer over a 28-d period. The
      increase in blood lead varied by a factor of about two. There was a similar two
      fold variability in the whole-body uptake (mean 14%) of a single oral dose of the
      short-lived tracer 203Pb. 2. The average elevations led to estimates of the
      potential increment from consumption of alcoholic beverages which accord broadly
      with epidemiological observation and which, if relevant to intakes of lead in
      table wine, raise the possibility of considerably elevated levels in the blood of
      avid consumers. 3. Rate constants inferred for removal of stable lead from blood
      were lower than reported following intake of the tracer, reflecting feedback of
      lead from other compartments.

PMID- 1354459
TI  - Aldrin and dieldrin residues in human fat, milk and blood serum collected from
      Delhi.
AB  - 1. Aldrin and dieldrin residues were monitored in the fat, breast milk and blood
      serum from female residents of Delhi. 2. The average aldrin and dieldrin contents
      were 0.048 and 0.099 ppb in adipose tissue, 0.003 and 0.060 ppb in breast milk
      and 0.004 and 0.002 ppb in blood serum, respectively. 3. The older donors
      contained higher levels of aldrin and dieldrin in their adipose tissue. 4.
      Primagravidae contained more of these chemicals in their breast milk. 5. A
      positive correlation was observed between the aldrin concentration in adipose
      tissue and breast milk, and that in adipose tissue and blood serum. Similarly, a
      significant correlation was found between dieldrin in adipose tissue and blood
      serum. 6. The levels of aldrin and dieldrin were low in samples from residents of
      Delhi when compared to those in developed countries.

PMID- 1354460
TI  - Fatal cyanide poisoning from cassava-based meal.
AB  - Three patients admitted to the Accident and Emergency Unit of Lagos University
      Teaching Hospital (LUTH) after eating a cassava based meal 'Gari' died shortly
      after admission. The patients vomited and complained of abdominal pain
      immediately after the meal. They were unconscious with renal failure and died of
      cardiopulmonary arrest. The cyanide levels in the blood and urine averaged 1.12
      and 0.54 mg l-1, respectively. Cassava contains cyanogenic glycosides which
      slowly release cyanide and this may have been responsible for the death of these
      patients. There is an urgent need to establish maximum tolerable levels of
      cyanide in 'Gari' and other cassava food products.

PMID- 1354461
TI  - Toxicological findings after fatal fenfluramine self-poisoning.
AB  - A fatal case involving the suicidal ingestion of fenfluramine is presented. The
      drug was quantified using gas chromatography. The blood concentration of
      fenfluramine was 7.46 mg l-1. Chronic use of fenfluramine was clearly
      demonstrated by the presence of drug in hair at 14.1 ng mg-1.

PMID- 1354462
TI  - An acute mercuric mercury poisoning: chemical speciation of hair mercury shows a
      peak of inorganic mercury value.
AB  - A woman ingested a dose of sublimate (approximately 0.9 g) in an attempted
      suicide. She survived and recovered in response to a combination of therapies
      including chelate (BAL) therapy, plasma exchange, haemodialysis and peritoneal
      dialysis. Serum inorganic mercury concentration, urinary inorganic mercury
      excretion and hair inorganic and organic mercury and selenium concentrations,
      along the length from the scalp to the distal part, were measured. Longitudinal
      analysis of hair, revealed a peak in inorganic mercury corresponding to the time
      of mercury ingestion. Organic mercury and selenium in the hair had different
      patterns of longitudinal variation from that of inorganic mercury. The biological
      half-life (23.5 d) of serum inorganic mercury levels was in good agreement with
      values previously reported in the literature.

PMID- 1354463
TI  - Does bismuth chelate influence lornoxicam absorption?

PMID- 1354464
TI  - Carcinogenicity of sulphadimidine.

PMID- 1354465
TI  - Cobalamin deficiency and the pathogenesis of nervous system disease.
AB  - Neuropathy commonly complicates cobalamin (Cb1) deficiency in humans, monkeys,
      fruit bats, and pigs. The neuropathy is characterized by demyelination of the
      posterolateral columns of the spinal cord (subacute combined degeneration). The
      lesion was thought to arise primarily from impairment of the adenosylcobalamin
      dependent methylmalonyl CoA mutase reaction, leading to the formation of abnormal
      odd-chain and branched-chain fatty acids and their incorporation into myelin with
      resultant demyelination. Data from recently developed animal models of the Cb1
      neuropathy induced by exposure to nitrous oxide do not substantiate this
      hypothesis, but rather identify impairment of the methylcobalamin-dependent
      methionine synthetase reaction as the more important basic defect. The key
      evidence for this hypothesis is the ability of methionine to delay the onset of
      Cb1 neuropathy in experimental Cb1 deficiency. In the Cb1-deficient pig,
      adenosylhomocysteine accumulates in neural tissue, presumably owing to the
      inability to recycle homocysteine via the defective methionine synthetase
      reaction. Accumulation of adenosylhomocysteine results in a fall in the
      adenosylmethionine:adenosylhomocysteine methylation ratio, and this change is
      believed to cause defective methylation and demyelination in the nervous system.
      However, in the Cb1 neuropathy in the fruit bat, adenosylhomocysteine does not
      accumulate in the nervous system, the methylation ratio does not change, and no
      defect can be demonstrated in the methylation of myelin lipid or basic protein.
      Although a central role for methionine in the pathogenesis of the Cb1 neuropathy
      has been established, defective methylation attendant upon impairment of the
      methionine synthetase reaction may not be the universal defect underlying the Cb1
      neuropathy. This would suggest that the methionine effect could be mediated via
      its role in formate metabolism or polyamine synthesis, or by some as yet
      unidentified pathway.

PMID- 1354466
TI  - CD8+ cell anti-HIV activity: nonlytic suppression of virus replication.

PMID- 1354468
TI  - FDA's policy statement for the development of new stereoisomeric drugs.

PMID- 1354467
TI  - CD4-binding of gp130 micelles isolated from SIVagmTYO-7.
AB  - The binding and binding inhibition of the SIVagmTYO-7 external glycoprotein gp130
      in micellar form to the CD4 molecule on human Molt-4 clone 8 cells was
      investigated. The best binding of gp130 to Molt-4 clone 8 cells occurred at pH
      5.5 to 6.5 at 37 degrees C after 4 h or at room temperature after 10 h. The
      dissociation constant of this reaction was 0.2-0.4 nM, with both soluble CD4 or
      CD4 on Molt-4 clone 8 cells. This value is close to 0.15 nM determined for the
      antihuman CD4 monoclonal antibody 30F16H5. After partial deglycosylation of
      gp130, a 90 kD product arose which still bound to CD4. Fully deglycosylated gp130
      of 60 kD was still immunoprecipitable, but had lost the CD4 binding activity.
      Lens culinaris agglutinin was able to inhibit the gp130-CD4 interaction very
      efficiently, while the agglutinin of Phaseolus vulgaris was half as efficient and
      Canavalia ensiformis was inefficient. CD4 binding of gp130 micelles was also
      inhibited with several anti CD4 monoclonal antibodies directed against the OKT4a
      epitope as well as with soluble recombinant CD4.

PMID- 1354469
TI  - Taxol improves outlook for lung, breast, and ovarian cancer.

PMID- 1354470
TI  - Regulation of mucosal immune responses by T lymphocytes: the effect of chronic
      CD4+ T cell deficiency on IgA synthesis.
AB  - Mechanisms of immune defence at the mucosal surface has been elucidated by recent
      advances in molecular and cellular immunology. IgA is undoubtedly the most
      important defense factor in the mucosal immune system. It has been shown that T
      cells are essential for the induction and regulation of IgA synthesis. In T cell
      regulation of IgA synthesis, various cytokines (e.g., TGF-beta, IL-2, IL-5, and
      IL-6) which are secreted by CD4+ T cells, play important roles for the induction
      and regulation of IgA isotype switching and terminal differentiation of sIgA+ B
      cells to become IgA producing cells. The chronic treatment of mice with anti-CD4
      mAb induced a market deficiency of CD4+ T cells in both mucosal and systemic
      tissues. IgA plasma cells were significantly reduced in treated mice when
      compared with normal mice (greater than 80% reduction), while the numbers of
      sIgA+ B cells in IgA inductive sites (e.g., PP) remained normal. CD4+ Th cells
      are a critical element for the induction of appropriate IgA responses in mucosal
      associated tissues. Elucidation of the precise cellular and molecular network for
      the regulation of mucosal immune defense system is important and useful for the
      consideration of prevention of infectious diseases. In this regard, the effective
      and sophisticated mucosal administration of vaccines using the concept of the
      common mucosal immune system should induce effective immune responses which
      prevent the pathogen from entering the host through large surface areas of
      mucosal membranes. This goal cannot be achieved without a more complete
      understanding of regulatory T cells and cytokines for mucosal immune responses.

PMID- 1354471
TI  - Innervation of mucosal immune cells in the gastrointestinal tract.
AB  - There is mounting evidence for interactions between the immune and peripheral
      nervous systems. Many regulatory molecules are candidate mediators for
      communication between inflammatory cells and nerves; however, the extent of
      targeting of neurotransmitters (and interleukins) as intersystem messengers has
      been somewhat overlooked. Lymphoid tissues are well supplied by nerves and the
      gastrointestinal lamina propria, which is populated by a variety of immune cell
      types, is densely innervated. One-half to two-thirds of mast cells are closely
      apposed to nerves in the intestinal mucosa, in both rodents and humans, and nerve
      stimulation has been reported to cause mast cell activation. Although less
      extensively studied, both eosinophils and plasma cells in the gastrointestinal
      mucosa are also positioned for interaction with nerves, and intra-epithelial
      leukocytes may be subject to diffusible neurally-derived mediators. Peyer's
      patches are relatively sparsely innervated but appear to express neuropeptide
      receptors in inflammatory conditions. Although the nerves in the mucosa have
      traditionally been thought of as a static component, recent experiments suggest
      that these may undergo extensive remodelling during nematode-induced
      inflammation. Such data suggest a dynamic interplay between the immune and
      nervous systems during inflammatory episodes in the gut, although considerable
      work is still needed to determine the importance of neuro-immune interactions in
      gastrointestinal homeostasis and inflammation.

PMID- 1354472
TI  - Global programme on AIDS. Unexplained CD4+ T-lymphocyte depletion in persons
      without evident HIV infection.

PMID- 1354474
TI  - Cancer in the very young child. Symposium proceedings. Leeds, 26-28 September
      1990.

PMID- 1354475
TI  - Psychiatry: all you need is drugs?

PMID- 1354473
TI  - Somatostatin binding in normal and malignant human gastrointestinal mucosa.
AB  - Somatostatin is a regulatory peptide implicated in the control of cellular
      proliferation in epithelial tissues and this regulation may occur directly via
      membrane bound receptor activation. The aim of this study was to investigate
      somatostatin binding in human gastrointestinal cancer and normal mucosa. Plasma
      membranes were prepared from specimens of tumour and normal mucosa from 51
      patients undergoing surgical resection for malignancy (28 gastric, 23
      colorectal). Using a competitive displacement assay, specific 125I-tyrosine-11
      somatostatin-14 binding to plasma membranes was assessed and and characterised in
      terms of receptor affinity (Kd) and maximum binding capacity (Bmax) as determined
      by Scatchard analysis. Specific low affinity (Kd = 166 nM), high capacity (Bmax =
      1.2 pmol mg-1 protein) somatostatin binding was demonstrated in 22 of the gastric
      cancers and 17 of the colorectal cancers (Kd = 140 nM, Bmax = 1.8 pmol mg-1
      protein). Similar affinity and binding capacity was demonstrable in normal
      mucosal samples. High affinity receptors for somatostatin were expressed by one
      gastric carcinoma (Kd = 0.9 nM; Bmax = 0.23 pmol mg-1 protein). Thus, low
      affinity, high capacity binding is a common feature of gastrointestinal tumours
      and normal mucosa, and high affinity receptors may occasionally be demonstrated.
      The functional significance of these low affinity binding sites requires
      elucidation to determine whether long-acting somatostatin analogues may have
      therapeutic benefit in gastrointestinal malignancy.

PMID- 1354476
TI  - Extended role: weathering the storm. Interview by Charlotte Alderman.

PMID- 1354477
TI  - Low-frequency restriction fragment analysis of Frankia strains (Actinomycetales).
AB  - Low-frequency restriction fragment analysis of more than 100 strains of the genus
      Frankia showed that restriction enzyme DraI (recognition site, TTT'AAA) gave rise
      to large DNA fragments (200 to 1,500 kb), which, when they were subjected to
      cluster analysis, reflected the host plants from which the strains were isolated.
      Our results support the conclusions of Lalonde and his colleagues (M. Lalonde, L.
      Simon, J. Bousquet, and A. Seguin, p. 671-680, in H. Bothe, F. J. de Bruijn, and
      W. E. Newton, ed., Nitrogen Fixation: Hundred Years After, 1988; P. Normand, P.
      Simonet, and R. Bardin, Mol. Gen. Genet. 213:238-246, 1988) and Fernandez et al.
      (M. P. Fernandez, H. Meugnier, P. A. D. Grimont, and R. Bardin, Int. J. Syst.
      Bacteriol. 39:424-429, 1989) that various biochemical and genomic analyses can
      give rise to groupings of Frankia strains that are consistent with the host
      plants from which the strains are isolated and that the resulting groups may form
      a basis for defining Frankia species.

PMID- 1354478
TI  - Differentiation of the subspecies of Campylobacter fetus by genomic sizing.
AB  - Campylobacter fetus subsp. fetus and C. fetus subsp. venerealis are currently
      differentiated by tolerance to glycine and by their epidemiology. Analysis of C.
      fetus DNA by pulsed-field gel electrophoresis, after digestion with the
      restriction endonucleases SmaI and SalI, was used to differentiate between the
      subspecies. All strains presently identified as C. fetus subsp. fetus had a
      genomic size of 1.1 Mb, whereas the majority of the C. fetus subsp. venerealis
      strains had a genomic size of 1.3 Mb. An additional group of strains, which were
      previously described as C. fetus subsp. venerealis biovar "intermedius" and were
      able to tolerate higher concentrations of glycine than the rest of the C. fetus
      subsp. venerealis strains, had an average genome size of 1.5 Mb. We suggest that
      pulsed-field gel electrophoresis may be useful as an additional aid in the
      differentiation of C. fetus strains at the subspecies level.

PMID- 1354479
TI  - Ribosomal DNA restriction analysis reveals genetic heterogeneity in Saccharomyces
      cerevisiae Meyen ex Hansen.
AB  - A ribosomal DNA restriction analysis of 17 strains belonging to the Saccharomyces
      cerevisiae complex revealed two major groups, one of which corresponded to
      Saccharomyces bayanus. Our results generally correlate with previously reported
      genetic and molecular data and support the conclusion that S. bayanus should be
      reinstated as a separate taxon.

PMID- 1354480
TI  - 6th Annual North American Cystic Fibrosis Conference. Washington, D.C., October
      15-18, 1992. Proceedings and Abstracts.

PMID- 1354481
TI  - Some technical parameters influencing the precision and accuracy of fragment size
      determination for RFLP's.
AB  - A comparison was carried out between 3 computer-assisted systems for the
      estimation of DNA fragment length: (1) the "Digitab" system (developed at our
      institute), (2) the FBI analysis system (FBI Quantico, USA) and (3) the BioImage
      system (Waters/Millipore, USA). Both the FBI system and the BioImage system were
      found to be much more precise than the manual Digitab system. In an additional
      experiment, a possible influence of the field strength on the "accuracy" of
      fragment size measurement was checked. Lowering the field strength to approx.
      1V/cm led to a statistically significant increase in the measured fragment size.

PMID- 1354482
TI  - Forensic identification of urine samples.
AB  - VNTR polymorphisms were investigated for the possible individualisation of human
      urine samples with reference to doping cases in sport. Investigations were
      carried out with the RFLP single locus system YNH24/Hinf I and the PCR-VNTR
      systems Apo B and COL2A1 (AMPFLPs) as well as SE 33 and TC 11 (STRs). Urine
      samples were tested using 3 different volumes (10 ml, 1 ml and 0.1 ml) after 2
      days and 2-5 weeks storage at 4 degrees C. Positive results were obtained for STR
      systems in all cases and with the smallest volume of urine tested (0.1 ml). The
      AMPFLP systems gave positive results in 4 out of 8 (Apo B) and 5 out of 8
      (COL2A1) samples and YNH24 was successful in 1 out of 3 samples. Negative results
      were obtained for the AMPFLP systems and YNH24 after longer storage periods
      whereas the STRs were positive.

PMID- 1354483
TI  - DNA recommendations--1992 report concerning recommendations of the DNA Commission
      of the International Society for Forensic Haemogenetics relating to the use of
      PCR-based polymorphisms.

PMID- 1354484
TI  - Sodium nitroprusside alters dark voltage and light responses in isolated retinal
      rods during whole-cell recording.
AB  - Dark voltage and light responses of isolated retinal rods of Rana esculenta were
      investigated by employing the whole-cell patch-clamp technique. When the
      recording pipette was filled with a medium devoid of nucleotides, a spontaneous
      hyperpolarization of the dark voltage partly due to a diffusional loss of cGMP
      and its precursor GTP and a retardation in the recovery of the light responses
      was observed. The larger part of the retardation of the light responses was
      prevented by 1 mM ATP. Addition of GTP attenuated the hyperpolarization, but did
      not abolish it completely. When the nitric-oxide-releasing substance sodium
      nitroprusside plus GTP was applied, the tendency of hyperpolarization disappeared
      and a stable dark voltage or even a slight depolarization was measured during the
      whole-cell recording period. Similar results were also obtained when GTP was
      given in combination with either EGTA or IBMX which are both known to interfere
      with the cGMP regulating enzymes in retinal rods. In addition to its effects on
      the dark voltage, an acceleration of the recovery phase of the light responses by
      sodium nitroprusside was also observed. Our observations strongly suggest that
      sodium nitroprusside activates guanylate cyclase in photoreceptors, as it does in
      other tissues, but we cannot exclude with certainty an effect on the
      phosphodiesterase.

PMID- 1354485
TI  - Circulating intercellular adhesion molecule-1 in melanoma patients: induction by
      interleukin-2 therapy.
AB  - Intercellular adhesion molecule-1 (ICAM-1, CD54), a molecule bound to the cell
      surface membrane, mediates various cell-cell interactions in inflammation and
      immunosurveillance. By means of a new specific enzyme-linked immunosorbent assay
      (ELISA) for soluble ICAM-1, free circulating ICAM-1 was measured in serum from
      five healthy volunteers, 10 melanoma patients at different stages of their
      disease, and eight patients receiving high-dose interleukin-2 (IL-2) for
      metastatic melanoma. No correlation between the concentration of circulating ICAM
      1 and the tumor burden could be detected. In melanoma patients receiving high
      dose IL-2, we observed an increase of circulating ICAM-1 of up to 200%, compared
      to the concentration prior to therapy, ranging between 4 and 13 ng/ml. The
      increase in circulating ICAM-1 was associated with the induction of tumor
      necrosis factor-alpha and interferon-gamma.

PMID- 1354486
TI  - Mediated Na(+)-independent transport of L-glutamate and L-cystine in 1- and 2
      cell mouse conceptuses.
AB  - L-Glutamate and L-cystine appeared to compete for transport via a mediated Na(+)
      independent transport process in 1- and 2-cell conceptuses. Not only did these
      substances competitively inhibit each others' uptake by conceptuses, but their Ki
      values for inhibition were about equal to their Km values for transport in 1-cell
      conceptuses. Moreover, the transport process interacted strongly with L-amino
      acids that had 3-6 atoms in a chain between their negatively charged groups,
      whereas it interacted weakly or not at all with amino acids that did not have
      these characteristics or that were N-methylated. Transport of anionic amino acids
      was not altered greatly by pH in the range 4.5-8.0, but transport of L-cystine
      was much faster at higher pH values. The slower cystine transport at lower pH
      values was due primarily to protonation of its second amino group. A small
      increase in the degree of deprotonation of cystine's carboxyl groups also
      probably contributed slightly to its faster transport at higher pH values. By all
      of these criteria, the transport process in conceptuses appears to be a form of
      amino acid transport system xc-. System xc- activity was several-fold higher in 1
      than in 2-cell conceptuses. Similarly, L-glutamate uptake by unfertilized eggs
      was relatively rapid, whereas it was much slower in immature, fully-grown
      oocytes. System xc- activity in 1-cell conceptuses also appeared to increase in
      response to the oxidative stress of culture, whereas no such increase was
      observed for 2-cell conceptuses. We suggest that this transient increase in the
      activity of system xc- activity during development of 2-cell conceptuses from
      immature, fully-grown oocytes could help protect unfertilized and fertilized eggs
      from oxidative stresses in situ.

PMID- 1354487
TI  - Proton transfer roles of lysine 64 and glutamic acid 64 replacing histidine 64 in
      the active site of human carbonic anhydrase II.
AB  - The CO2 hydration activities of cloned human carbonic anhydrase II (carbonate
      hydro-lyase, EC 4.2.1.1) and variants with Lys, Glu, Gln or Ala replacing His at
      sequence position 64 have been measured in a variety of different buffers in the
      pH range 6-9. The variants with Lys-64, Gln-64 and Ala-64 showed non-Michaelis
      Menten behavior under some conditions, apparent substrate inhibition being
      prominent near pH 9. However, asymptotic Michaelis-Menten parameters could be
      estimated for the limit of low substrate concentrations. All variants show
      distinct buffer specificities, and imidazole derivatives, Ches and phosphate
      buffers yield higher kcat values that Bicine, Taps and Mops buffers under
      otherwise similar conditions. These results are interpreted in terms of different
      pathways for a rate-limiting proton transfer. In unmodified enzyme, the very high
      catalytic activity depends on His-64 functioning as an efficient proton transfer
      group, but this pathway is not available in the variants with Gln-64 and Ala-64.
      Imidazoles, Ches and phosphate are thought to participate in a metal center-to
      buffer proton transfer pathway, whereas Bicine, Taps, Mops and Mes appear to lack
      this capacity, so that the rate-limiting proton transfer occurs in a metal center
      to-bulk water pathway for these variants. The Lys-64 and Glu-64 variants give
      significantly higher kcat values in Taps, Mops and Mes buffers than the Ala-64
      and Gln-64 variants. The pH dependencies of these kcat values are compatible with
      the hypothesis that Lys-64 and Glu-64 can function as proton transfer groups.
      Thus, at pH near 9, Lys-64 appears to be only 5-times less efficient than His-64,
      while Glu-64 is inefficient. At pH 6, Lys-64 is an inefficient proton transfer
      group, but Glu-64 is only 2-3-times less efficient than His-64. The data indicate
      that Lys-64 and Glu-64 have pKa values near 8 and below 6, respectively.

PMID- 1354488
TI  - Expression of haptoglobin receptors in human hepatoma cells.
AB  - The uptake of radio-labeled hemoglobin-haptoglobin complex (Hb-Hp) by human
      hepatoma PLC/PRF/5 and HepG2 cells was investigated in an attempt to characterize
      the uptake process and intracellular transport. Human hepatoma cells took up Hb
      Hp in a receptor-mediated manner. Scatchard analysis of binding revealed that
      PLC/PRF/5 and HepG2 cells exhibited about 21,000 and 63,000 haptoglobin
      receptors/cell, with a dissociation constant (Kd) of 8.0 and 17 nM, respectively.
      Human hepatocytes in primary culture also expressed about 84,000 receptors/cells,
      with a Kd of 7.4 nM. The hemoglobin-haptoglobin complex was internalized and
      subsequently the internalized Hb-Hp was slowly degraded in the cells.
      Preincubation of the cells with Hb-Hp resulted in a decrease in binding of the
      radioactive Hb-Hp to the cell surface, and was accompanied with an accumulation
      of intracellular receptors. The uptake of Hb-Hp by the cells was not inhibited by
      100 microM chloroquine or by 10 mM methylamine, but was inhibited by 50 microM
      monodansylcadaverine. Hemoglobin-heme taken up by the cells induced microsomal
      heme oxygenase. Thus, human hepatoma PLC/PRF/5 and HepG2 cells can take up Hb-Hp
      by haptoglobin receptor-mediated endocytosis and Hb-Hp probably causes
      translocation of the haptoglobin receptors from the cell surface to the cell
      interior where they can be degraded. The internalized heme-moiety of hemoglobin
      can regulate the expression of heme oxygenase.

PMID- 1354489
TI  - Influence of wearing masks on the density of airborne bacteria in the vicinity of
      the surgical wound.
AB  - To find out if the wearing of masks influenced the number of colony forming units
      (CFU) of bacteria in the vicinity of the wound, 14 operations on the thyroid
      gland were divided in 30 min periods during which personnel were randomly
      allocated to wear or not to wear masks. There was at least one period with, and
      one without masks during each operation. Air was sampled 20 cm from the wound
      using a Sartorius membrane filter sampler. There were no significant differences
      between the groups in either numbers of CFU or species of pathogenic bacteria
      found.

PMID- 1354490
TI  - Effect of suture technique on early healing of intestinal anastomoses in rats.
AB  - OBJECTIVE: To see if the site and tension of sutures had any influence on early
      breaking strength in intestinal anastomoses. MATERIAL: 161 Male Wistar rats.
      INTERVENTIONS: First experiment: after laparotomy and division of the ileum an
      inverted end to end anastomosis was made in a single layer with 14 interrupted
      sutures of 7/0 polypropylene. All sutures were inserted 3 mm from the cut edges.
      The rats were randomly allocated to one of four groups according to the size of
      the loop of suture used: tight (n = 38), 0.4 mm (n = 22), 0.9 mm (n = 35), or 2.0
      mm (n = 24). Second experiment: the method used was the same except that sutures
      were placed 1.5 mm from the cut edges and the rats were randomly allocated to one
      of two groups according to the size of loop of suture--tight (n = 20), or 0.9 mm
      (n = 22). MAIN OUTCOME MEASURES: Breaking strength measured in a tensiometer
      (both experiments); and myeloperoxidase activity/g tissue, hydroxyproline content
      and solubility/biopsy specimen (first experiment only). RESULTS: Breaking
      strength decreased proportionally the tighter the sutures were tied, and the
      differences were significantly greater when the sutures were placed closer to the
      cut edges. Anastomotic myeloperoxidase activity, hydroxyproline content, and
      soluble: total hydroxyproline ratio were similar in all groups. CONCLUSION: Tight
      sutures may promote proteolytic tissue degradation by reducing the local
      availability of circulating proteinase inhibitors.

PMID- 1354491
TI  - Stab wounds to the pericardium and heart: an analysis of 85 consecutive patients.
AB  - OBJECTIVE: To audit all stab wounds of the pericardium and heart treated by a
      policy of immediate exploration over a period of 17 years, and identify any
      factors predictive of outcome. DESIGN: Retrospective study. SETTING: Urban
      referral centre. SUBJECTS: 85 consecutive patients with stab wounds of
      pericardium and heart. INTERVENTIONS: Immediate exploration. MAIN OUTCOME
      MEASURES: Mortality and morbidity. RESULTS: Eleven patients died (13%), 10 of
      them on the operating table. No powerful predictor of outcome was identified, but
      measurable blood pressure on admission (p = 0.04) and a low cardiac trauma index
      score (p = 0.07) seemed to be associated with survival. CONCLUSION: Some
      unrecordable factors--for example, the skill of the team on duty--may have had a
      considerable influence on outcome.

PMID- 1354492
TI  - Catheter-related complications of continuous ambulatory peritoneal dialysis.
AB  - OBJECTIVE: To assess the effectiveness of continuous ambulatory peritoneal
      dialysis (CAPD) with particular reference to morbidity. DESIGN: Open study.
      SETTING: Two city general hospitals. SUBJECTS: 104 Adults and 11 children with
      end stage renal failure. MAIN OUTCOME MEASURE: Morbidity. RESULTS: There were 29
      complications (25%), the most common being obstruction of the tube (n = 8, 7%),
      and migration of the tube (n = 7, 6%). Others were peritonitis (n = 5),
      haemorrhage (n = 4), infection at the exit site (n = 3), and leakage of fluid (n
      = 2). All were readily treatable. CONCLUSIONS: Fixing the catheter in two places
      may prevent its migration. The complication rate of CAPD is acceptable, and in
      children with end stage renal failure it is a suitable alternative to
      haemodialysis while they are waiting for renal transplantation.

PMID- 1354493
TI  - Assessment of the physiological importance of iliac artery stenosis by laser
      Doppler flowmetry in pigs.
AB  - OBJECTIVE: To test the hypothesis that a curve with two peak values (double hump)
      recorded by laser Doppler flowmetry over the skin of the lower limb during
      postocclusive hyperaemia reflects pathological vascular resistance in the
      aortoiliac segment. DESIGN: Open study. MATERIAL: Six Norwegian Landrace pigs.
      INTERVENTION: Arterial stenoses were induced in the external iliac arteries. MAIN
      OUTCOME MEASURES: Presence of double humped laser Doppler curves, relative
      decrease in laser Doppler flux between the two peaks, and time taken to reach
      peak hyperaemic flux. RESULTS: Double humped curves were seen only when arterial
      stenoses were present. The relative decrease in laser Doppler flux between the
      two peaks, and the time to reach peak hyperaemic flux were related to the blood
      pressure gradient (mmHg) at the stenosis (r = 0.88 and 0.83, p less than 0.0001).
      The laser Doppler curve pattern can be explained by similar dynamic changes in
      arterial blood pressure distal to the tourniquet during hyperaemia. CONCLUSION:
      These results confirm the hypothesis, and suggest that laser Doppler flowmetry
      recordings of postocclusive hyperaemia may be a non-invasive way of assessing the
      condition of the iliac artery.

PMID- 1354495
TI  - Hypercalcaemia and pancreatic ultrastructure in cats.
AB  - OBJECTIVE: To study the effects of local and systemic infusions of calcium on the
      ultrastructure of the pancreas in cats. DESIGN: Controlled study. INTERVENTIONS:
      Three groups of four cats each had local infusions (into the splenic artery) of
      calcium gluconate 0.6 mmol/kg.hour or potassium chloride 1.1 mmol/kg.hour, or
      sodium chloride 0.9%, for three hours. Two groups of eight cats each had systemic
      infusions (into the jugular vein) of either calcium gluconate 0.6 mmol/kg.hour or
      sodium chloride 0.9%, for twelve hours. In the group that was given calcium, the
      infusion rate was reduced after three hours to 0.3 mmol/kg.hour to maintain the
      hypercalcaemic state for a further nine hours. RESULTS: Local infusion of calcium
      caused destruction of acinar cells with hydropic degeneration of nuclei,
      discharge of cell organelles into the interstitial spaces, and extravasation of
      red blood cells but no apparent damage to the capillaries. There were no
      ultrastructural changes of any importance in the groups that received potassium
      or sodium chloride. Systemic infusion of calcium resulted in a 1.8 fold increase
      in the ionised calcium concentration in the serum, progressive signs of
      overstimulation of the Golgi apparatus with hypertrophy, fusion of condensing
      vacuoles, and disruption of the acinar cell polarization. This was followed by
      clumping of nuclear chromatin and destruction of acinar cells. CONCLUSION: Acute
      pancreatitis in cats can result from stimulation and destruction of acinar cells
      by hypercalcaemia.

PMID- 1354494
TI  - Association between haematoma after inguinal hernia repair and site of heparin
      injection.
AB  - OBJECTIVE: To see if subcutaneous heparin prophylaxis against deep vein
      thrombosis and pulmonary embolism given into the abdominal wall caused more
      haematomas after repair of inguinal hernia than the same dose given into the
      shoulder. DESIGN: Random control trial. SETTING: District hospital. SUBJECTS: 101
      consecutive patients admitted for elective inguinal hernia repair. INTERVENTIONS:
      Four injections of sodium heparin 5,000 IU given either into the abdominal wall
      or the shoulder, the first two hours, before, and the last 24 hours after
      operation. MAIN OUTCOME MEASURE: Incidence of haematoma after operation. RESULTS:
      There was no significant difference in the incidence of haematoma between the
      groups. Haematoma formation was associated with a fall in systolic blood pressure
      of more than 25% (p = 0.055), which in turn was significantly associated with age
      over 60 years (p less than 0.0003). CONCLUSION: Injection of heparin
      subcutaneously into the abdominal wall does not lead to more wound haematomas
      than injection into the shoulder. Haematoma formation seems to be associated with
      a drop in systolic blood pressure of 25% or more, and thus requires further
      investigation.

PMID- 1354496
TI  - Peroperative endotoxin concentrations in portal and peripheral venous blood in
      patients undergoing right hemicolectomy for carcinoma.
AB  - OBJECTIVE: To find out the incidence of systemic and portal endotoxaemia in a
      homogeneous group of patients with colonic cancer undergoing a standard
      operation, and to compare them with a control group with benign disease. DESIGN:
      Open study. SETTING: Department of Surgery, Stockholm Soderhospital. SUBJECTS: 15
      of 17 consecutive patients admitted for right hemicolectomy for cancer, and four
      control subjects (one with angiodysplasia, and three with ulcerative colitis) who
      were to undergo right hemicolectomy and proctocolectomy. INTERVENTION: After
      mobilisation of the colon, 10 ml samples of blood were taken simultaneously from
      a mesocolic vein, and from an antecubital vein, for assay of endotoxin. RESULTS:
      Raised concentrations of endotoxin were found in the portal blood of 4 of the 15
      patients with cancer, and in two of the four with benign disease. One of the four
      with cancer also had a raised value in peripheral blood. There was no correlation
      between increased endotoxin concentration and tumour size, Dukes' stage, or
      development of infective complications. CONCLUSION: Pronounced concentrations of
      endotoxin are found only rarely in patients undergoing right hemicolectomy for
      cancer. The most likely explanation is translocation of endotoxin through mucosa
      damaged by an ulcerating tumour.

PMID- 1354497
TI  - Postoperative follow-up of patients with colorectal carcinoma by colonoscopy.
AB  - OBJECTIVE: To find out if colonoscopy is of use in the follow-up of patients who
      have been operated on for colorectal carcinoma. DESIGN: Retrospective study.
      SETTING: Department of diagnostic radiology, university hospital. SUBJECTS: 390
      consecutive patients operated on for colorectal carcinoma during the 10-year
      period 1981 to 1990. MAIN OUTCOME MEASURES: Number of recurrences, synchronous of
      metachronous tumours, and number and size of adenomas found on colonoscopy.
      RESULTS: Neoplastic lesions were found in 175 (45%) of the 390 patients studied.
      There were 14 anastomotic recurrences and 12 new primary carcinomas. At operation
      for recurrent tumours Dukes' A or B lesions were found in half of the 14 patients
      who had no symptoms, and a quarter of the 12 who had had symptoms. Those with
      recurrent carcinoma were younger than those without. Adenomas 1 cm in diameter or
      more were found in 44 patients and 104 had adenomas less than 1 cm. In addition
      one carcinoid was found. CONCLUSION: Colonoscopy gave a high yield of neoplastic
      lesions when used to follow-up patients after resection of colorectal carcinoma,
      particularly at six months, and resulted in half the recurrent carcinomas being
      diagnosed before the patients had symptoms. We recommend its use for follow-up of
      high risk patients, but further studies are needed to establish the optimum time
      intervals.

PMID- 1354498
TI  - New operative technique for recurrent pelvic malignancy. Omental wrapping and
      transfer of gracilis myocutaneous island flap.

PMID- 1354499
TI  - Digital gangrene after accidental intra-arterial injection of phenytoin
      (epanutin).
AB  - A case is described in which inadvertent intra-arterial injection of phenytoin
      led to digital gangrene, with arteriography showing occlusion of the digital
      arteries, necessitating amputation of fingers. The high alkalinity of phenytoin
      is strongly irritant to vessel walls. Intravenous injection of phenytoin should
      be given only with great care and in emergencies, preferably avoiding the cubital
      fossa.

PMID- 1354501
TI  - Primary benign ulcer of the gall bladder.
AB  - It is sometimes impossible to come to a final diagnosis in patients with
      dyspepsia and upper abdominal pain in spite of extensive investigation. Such
      patients are usually given vague diagnoses like "non-ulcer dyspepsia" and they
      represent an important diagnostic challenge.

PMID- 1354500
TI  - Decrease in arterial ketone body ratio indicating graft dysfunction after liver
      transplantation.
AB  - In 3 cases of living related liver transplantation, arterial ketone body ratio
      (AKBR) showed secondary decrease in the early postoperative period, indicating
      the graft dysfunction more rapidly and sensitively than other liver function
      tests. Significance of AKBR for monitoring the graft function in postoperative
      management after liver transplantation is discussed.

PMID- 1354502
TI  - A troublesome colostomy treated with liposuction.

PMID- 1354503
TI  - Time course of transmitter release calculated from simulations of a calcium
      diffusion model.
AB  - A three-dimensional presynaptic calcium diffusion model developed to account for
      characteristics of transmitter release was modified to provide for binding of
      calcium to a receptor and subsequent triggering of exocytosis. When low affinity
      (20 microM) and rapid kinetics were assumed for the calcium receptor triggering
      exocytosis, and stimulus parameters were selected to match those of experiments,
      the simulations predicted a virtual invariance of the time course of transmitter
      release to paired stimulation, stimulation with pulses of different amplitude,
      and stimulation in different calcium solutions. The large temperature sensitivity
      of experimental release time course was explained by a temperature sensitivity of
      the model's final rate limiting exocytotic process. Inclusion of calcium tail
      currents and a saturable buffer with finite binding kinetics resulted in high
      peak calcium transients near release sites, exceeding 100 microM. Models with a
      single class of calcium binding site to the secretory trigger molecule failed to
      produce sufficient synaptic facilitation under this condition. When at least one
      calcium ion binds to a different site having higher affinity and slow kinetics,
      facilitation again reaches levels similar to those seen experimentally. It is
      possible that the neurosecretory trigger molecule reacts with calcium at more
      than one class of binding site.

PMID- 1354504
TI  - Enzymatic and chemical demethylenation of (methylenedioxy)amphetamine and
      (methylenedioxy)methamphetamine by rat brain microsomes.
AB  - The metabolism of (methylenedioxy)amphetamine (MDA) and
      (methylenedioxy)methamphetamine (MDMA) was examined in microsomal preparations
      from rat brains. The products generated from MDA and MDMA were identified as
      dihydroxyamphetamine (DHA) and dihydroxymethamphetamine (DHMA), respectively. The
      demethylenation reaction required NADPH and was strongly inhibited by CO/O2 (4:1
      v/v), suggesting that the formation of DHA and DHMA is mediated by cytochrome
      P450. The conversion was inhibited by desipramine, imipramine, and methimazole,
      whereas SKF-525A and alpha-naphthoflavone had little effect. Lineweaver-Burk
      plots of MDA and MDMA demethylenation were biphasic in both cases, indicating
      that multiple isozymes may participate in the oxidation. The microsomal
      preparation showed no significant stereoselectivity in the demethylenation of
      either MDA or MDMA. Catechol formation differed with the incubation buffer and
      was 2.6 times greater when phosphate rather than HEPES buffer was used. This
      difference disappeared, however, when desferrioxamine B methanesulfonate
      (desferal) and hydroxyl radical (.OH) scavenging agents were added to either
      buffer. The demethylenation was also sensitive to catalase and was stimulated by
      the addition of ferric ion and EDTA to the microsomal incubation mixture. These
      results indicate that the demethylenation of MDA and MDMA by rat brain microsomes
      has a cytochrome P450-mediated component as well as a chemical component
      involving .OH.

PMID- 1354506
TI  - Gestational trophoblastic diseases: recent advances in the understanding of
      cytogenetics, histopathology, and natural history.
AB  - Our understanding of gestational trophoblastic diseases has progressed
      considerably in recent years in terms of our knowledge of their cytogenetic
      origin, histopathology, and natural history. Advances in molecular biology have
      been applied to the study of gestational trophoblastic diseases, providing new
      insights into their pathogenesis. Molecular biologic studies have now clearly
      demonstrated that complete molar pregnancies result from fertilization of an
      anuclear, "empty" ovum. Improved understanding of the cytogenetics and biology of
      gestational trophoblastic diseases may well contribute to further advances in
      patient care.

PMID- 1354505
TI  - Nonsurgical treatment of urinary incontinence.
AB  - Genuine stress urinary incontinence can be treated by surgical or nonsurgical
      methods. Conservative treatments include pelvic muscle exercises, hormonal and
      nonhormonal pharmacologic therapy, and functional electrical stimulation with
      vaginal or anal electrodes. All of these methods improve or cure stress
      incontinence in a significant proportion of selected women, with less cost and
      morbidity. Patients with genuine stress incontinence generally should have a
      trial of conservative therapy before corrective surgery is offered. Behavioral
      and pharmacologic methods, alone and in combination, are used for women with
      detrusor instability. Behavioral regimens, including bladder retraining and
      biofeedback, are particularly effective for urge and stress incontinence, but are
      dependent on compliance and motivation of both patient and caregiver. Drug
      therapy is effective, but with potential morbidity. As with genuine stress
      incontinence, surgical methods should only be employed for patients with detrusor
      instability who do not respond to nonsurgical treatment.

PMID- 1354507
TI  - Alzheimer's disease: relationship of cognition and behavior to neurochemistry.
AB  - Alzheimer's disease is characterized by loss of cells and synapses in specific
      neural systems. The development of more effective therapies will depend on
      understanding the relationships between this pathology and the cognitive and
      behavioral impairments. In this review, focusing primarily on work in our
      laboratory, we will examine both classic and neuropeptide neurotransmitter
      systems and will discuss conceptual and methodological problems in relating
      clinical and biological measures.

PMID- 1354508
TI  - Circulating levels and liver tissue distribution of intercellular adhesion
      molecule-1 during beta-interferon therapy of hepatitis C virus-associated chronic
      active liver disease.
AB  - Intercellular adhesion molecule-1, an immunoglobulin supergene family member, is
      known to account for important steps in cell activation and the immune response.
      By a non-isotopic slot-dot immunoblotting assay, we measured circulating levels
      of intercellular adhesion molecule-1 in 26 patients with hepatitis C virus
      associated chronic active liver disease before and after beta-interferon therapy,
      in 6 patients with non-A, non-B acute self-limiting hepatitis and in 13 healthy
      subjects. Circulating intercellular adhesion molecule-1 was found in 10 of 13
      (77%) normal controls at low concentrations which were not statistically
      different from those measured in patients with hepatitis C virus-associated
      chronic active liver disease responsive to beta-interferon, whereas significantly
      higher levels were found in unresponsive patients. Higher serum intercellular
      adhesion molecule-1 levels were found in 4 of 10 (40%) beta-interferon-responsive
      patients compared with 13 of 16 (18%) unresponsive patients. Intercellular
      adhesion molecule-1 levels persisted after discontinuation of beta-interferon
      treatment and did not correlate with hepatocytolysis (as indicated by alanine
      aminotransferase serum activity) either in chronic active liver disease or acute
      hepatitis. However, a good correlation was found between intercellular adhesion
      molecule-1 and its expression on liver cells, thus emphasizing that induced
      circulating levels may reflect the state of activation at the sites of the
      inflammatory process. These data strongly support the view that intercellular
      adhesion molecule-1 plays an important role in liver cell damage in hepatitis C
      virus-associated acute and chronic liver disease, and that its circulating levels
      may be a good prognostic parameter of responsiveness to beta-interferon therapy.

PMID- 1354509
TI  - Suspected chemoreceptors in coelenterates and ctenophores.
AB  - Chemoreceptors in coelenterates and ctenophores have not been identified with
      certainty. Among prospective chemoreceptive cells are the sensory nerve cells,
      the cnidocyst-bearing cnidocytes, and the epitheliomuscular cells that are likely
      to be involved in feeding or aggression. Both behaviors are mediated by
      coordinated chemical and mechanical reception. This is reflected in the close
      apposition of putative chemo- and mechanoreceptors. Among the structures that
      have been designated as likely chemo- and/or mechanoreceptors are stereocilia,
      kinocilia, and/or microvilli which are universally present on all the putative
      chemoreceptor complexes, while gland cells and mucous secretions are prevalent.
      Evidence that the actin-containing stereocilia are chemically modulated
      mechanoreceptors is presented for several forms.

PMID- 1354510
TI  - Narcotic use in the hospital: reasonably safe?
AB  - OBJECTIVE: To determine the causes and frequency of overdoses associated with the
      administration of opioid analgesics in hospitalized patients. DESIGN: Case
      series. SETTING: Two acute care teaching hospitals. PATIENTS: Eighty-one
      hospitalized patients who received naloxone for a clinically suspected narcotic
      overdose. INTERVENTIONS: Three investigators reviewed each patient who received
      naloxone during a 12-month period. The patients were judged to have a narcotic
      overdose if caregivers documented an immediate improvement in mental status,
      respiratory rate, or blood pressure after naloxone administration. MAIN OUTCOME
      MEASURES: The number and causes of narcotic overdoses were determined. The
      frequency of morphine and meperidine overdoses was calculated. The number of
      incidents reported using incident or adverse drug reaction reports or the
      appropriate International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9-CM) code. RESULTS: In the 22 overdoses that occurred, 14 (64
      percent) were caused by medication prescribing, compounding, or administration
      errors and potentially were preventable. The remaining eight patients experienced
      an overdose despite receiving appropriate amounts of opioids. The frequency of
      overdoses was 0.4 and 0.2 percent of total patients receiving morphine or
      meperidine, respectively, at the two hospitals. Nonreporting of these narcotic
      overdoses was frequent. In one hospital, 1 incident report and 3 adverse drug
      reactions were reported for 17 overdoses. At the second hospital, 1 incident
      report and 1 adverse drug reaction were reported for 6 overdoses. None of the
      patient charts included an ICD-9-CM code that documented the problem.
      CONCLUSIONS: The causes of overdoses are not limited to prescribing and
      administration errors. Some patients, despite proper execution of appropriate
      orders, develop a narcotic overdose. Caregivers must be aware of this problem and
      monitor patients for a decrease in mental status and respiratory rate. In
      addition, we conclude that an important number of hospitalized patients develop
      an overdose even though the frequency is low related to the number of patients
      receiving narcotics.

PMID- 1354511
TI  - Propafenone-induced liver injury.
AB  - OBJECTIVE: To describe propafenone-induced liver injury. DESIGN: Retrospective
      case report. SETTING: Referred care in a large tertiary care center. Laboratory
      tests were performed at the auxiliary site and the tertiary care center. PATIENT:
      A 71-year-old woman with atrial fibrillation developed elevations of greater than
      two times the upper limit of normal in alkaline phosphatase (ALK), alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), and gamma
      glutamyltransferase (GGT) after initiation of propafenone therapy. INTERVENTIONS:
      Studies included serial measurements of ALK, ALT, AST, and GGT. RESULTS: The
      patient developed elevations of greater than two times the upper limit of normal
      in ALK, ALT, and AST, one month after initiating propafenone therapy. The
      propafenone dose was decreased from 900 to 675 mg/d and, ten days later, the ALK,
      ALT, and AST were decreased slightly, but still above the upper limit of normal.
      One month later, serum transaminases had returned to baseline, but propafenone
      therapy was discontinued because of recurrent atrial fibrillation, persistent
      elevation in ALK, and elevation in GGT. Two months after discontinuing
      propafenone, serum aminotransaminase and ALK concentrations had normalized and
      GGT had decreased and remained only slightly elevated. CONCLUSIONS: The
      occurrence of liver injury secondary to propafenone therapy is rare. Reported
      cases appear to be secondary to hepatocellular injury, cholestasis, or a
      combination of the two. In this case, the pattern demonstrated by elevations in
      liver enzymes may be classified as acute cholestatic liver injury. Because the
      reported incidence is 0.1-0.2 percent and there are no known fatalities secondary
      to propafenone liver injury, routine monitoring of liver function tests in all
      patients receiving propafenone cannot be recommended at this time. Baseline liver
      function tests prior to initiating propafenone therapy with follow-up laboratory
      studies one month later are recommended in patients with known liver dysfunction.
      If elevations are noted, a reduction in dose may result in lower liver enzyme
      concentrations, although discontinuation of therapy may be required in some
      cases.

PMID- 1354512
TI  - Familial primary hyperparathyroidism: study of the pedigree in three generations.
AB  - The familial occurrence of primary hyperparathyroidism in which the proband is a
      55-year-old man is reported. His 58-year-old sister and 40-year-old brother had
      undergone partial parathyroidectomy, and histological examination revealed
      hyperplasia in both cases. Their father and a daughter of the proband had a
      history of nephrolithiasis. The three siblings showed high levels of plasma
      parathyroid hormone (even the two postoperative cases). All of them had a history
      of nephrolithiasis and peptic ulcers. In the proband, image studies did not
      reveal any abnormality in the neck region. At present, the three cases do not
      exhibit any abnormalities in the pancreas or the pituitary by imaging studies and
      endocrine tests.

PMID- 1354513
TI  - Proceedings of the Workshop on General Population Exposure to Gasoline.
      Annapolis, Maryland, 12-14 December 1990.

PMID- 1354515
TI  - Proceedings of the symposium on Foetal and Neonatal Cell Transplantation and
      Retroviral Gene Therapy. Annecy, France, January 5-8, 1992.

PMID- 1354514
TI  - Physician failure to record alcohol use history when prescribing benzodiazepines.
AB  - The purpose of this pilot study was (1) to determine the proportion of patients
      in an ambulatory medical clinic who have an alcohol history recorded when
      prescribed benzodiazepines, and (2) to assess the adequacy of the alcohol history
      when obtained. Medical records of 35 outpatients who obtained prescriptions for
      benzodiazepines at a large inner-city teaching hospital medical clinic were
      audited. In none of the records was there evidence that the physician had
      sufficient knowledge of the patient's alcohol use to safely prescribe a
      benzodiazepine. In 57% of the records, no information about alcohol use was
      recorded. In the remaining 15 medical records, the information recorded was
      limited. The implications of prescribing benzodiazepines without knowledge of
      drinking status are discussed.

PMID- 1354517
TI  - Human cord blood: a source of transplantable stem cells?
AB  - In a preliminary study we have shown that optimally collected human umbilical
      cord (HUC) blood cells grow significantly better in long term cultures (LTC) than
      normal adult marrow cells (NBM) p = 0.0007. The LTC findings are supported by the
      observation in clonogenic assay that a similar number of GM-CFC colonies can be
      grown from HUC blood and NBM mononuclear cells (MNC). Also there is a trend
      towards a higher proportion of primitive erythroid (BFU-E) and primitive
      megakaryocyte colonies (MK-CFC containing greater than 20 cells) in HUC blood
      compared with NBM. We suggest that further work on the feasibility of a HLA
      typed, cryopreserved HUC blood bank as a source of unrelated haemopoietic 'stem'
      cells for clinical transplantation is indicated.

PMID- 1354516
TI  - Hematopoietic progenitors cells in cord blood.
AB  - Human umbilical cord blood was evaluated as an alternative to bone marrow as a
      source of stem cells for hematopoietic transplantation. In order to define an
      optimal collection procedure, we have studied the parameters that influence the
      collection, handling and storage of cord blood. We have attempted to correlate
      the quality of the samples with obstetrical and neonatal parameters. Using
      culture techniques we have studied the long term viability of the cells. Cell
      separation was also investigated. Our results suggest that most of the sample
      collected could be suitable for transplantation, in term of progenitors. However
      the observed variability between samples suggest that an efficient control of the
      quality of the samples is important.

PMID- 1354518
TI  - Clinical applications of stem cell transfusion from cord blood and rationale for
      cord blood banking.
AB  - Umbilical cord blood collected and cryopreserved at birth contains enough
      hematopoietic progenitor stem cells for engraftment. HLA identical sibling cord
      blood transplant has been performed for the first time, in a child with Fanconi
      anemia. Three years latter, this child is alive with a complete donor type bone
      marrow. Since this first attempt, several other patients with other diseases have
      been transplanted successfully. Cord blood banking is a safe and easy procedure.
      Due to the high proliferative capacity of neonatal hematopoietic progenitors and
      to the relative immunological functional immaturity of neonatal lymphocytes cord
      blood cells could be used for matched unrelated or partially mismatched
      transplants.

PMID- 1354519
TI  - Fetal liver transplants.
AB  - Transplants of hematopoietic stem cells derived from fetal liver during the
      second trimester of pregnancy can restore hematopoiesis in animals and humans
      with bone marrow failure. These cells also have a reduced likelihood of causing
      graft-versus-host disease. Because fetal liver derived hematopoietic stem cells
      are relatively pure and considerable proliferative potential, they may be
      reasonable targets for studies of gene modification. Other possible uses of fetal
      liver derived stem cells are also considered as are results of fetal liver
      transplants in animals and humans. These data are compared to alternative sources
      of hematopoietic stem cells including bone marrow and umbilical cord and adult
      blood.

PMID- 1354520
TI  - In utero transplantation of stem cells in humans: immunological aspects and
      clinical follow-up of patients.
AB  - Four human fetuses were treated by transplantation of human fetal liver stem
      cells. Two of them had severe immunodeficiency disease and the two other ones had
      thalassemia major. Three of these in utero transplants were followed by
      engraftment. The three patients are now born: the first one is now very healthy
      thanks to the reconstitution of cell-mediated immunity associated with this
      transplant, and he lives normally at home; the two other ones, who have been more
      recently treated, have a significant improvement of their condition and they also
      live normally at home. This procedure, for the first time used in humans, has
      therefore demonstrated its feasibility and its efficacy: during early fetal
      development, foreign cells engraft readily and may result in cure or significant
      correction of a large variety of inherited diseases.

PMID- 1354521
TI  - T cell repertoire and tolerance after fetal stem cell transplantation.
AB  - We studied the T cell repertoire and the mechanism of tolerance in two patients
      with severe combined immunodeficiency transplanted with HLA mismatched fetal
      liver stem cells. They are 17 and 5 years old now, healthy, and show normal
      immunoresponses to recall antigens. Their T cells are of donor origin, whereas
      monocytes and B cells remained of the host. The NK cells have different sources
      since in one patient they derive from the donor and in the other one from the
      host. Despite the HLA mismatch between donor and host cells, no acute or chronic
      graft-versus-host disease was observed. In vitro experiments with PBMC showed
      specific nonresponsiveness for the HLA antigens expressed by the host cells.
      However, an extensive clonal analysis showed that CD4+ and CD8+ host-reactive T
      cell clones recognizing class II and class I HLA molecules of the host,
      respectively, were present in the peripheral blood of both patients. Limiting
      dilution experiments indicated that the frequency of CD8+ host-reactive cells was
      in the same range as that observed for alloreactive T cells. In contrast, no
      donor reactive CD8+ T cells could be isolated. Host-reactive CD4+ and CD8+ T cell
      clones were normal in their capacity to produce IL-2, IFN-gamma, GM-CSF and IL-5,
      but they failed completely to synthesize IL-4. In addition, CD4+ T cell clones
      from patient RV secreted very high levels of IL-10. Interestingly, exogenous IL
      10 was able to inhibit the proliferative responses of the CD4+ host-reactive T
      cell clones. Our data demonstrate that host-reactive cells are not deleted from
      the donor T cell repertoire following allogenic fetal liver stem cell
      transplantation. Therefore, in vivo tolerance between the host and the donor is
      maintained by a peripheral autoregulatory mechanism in which cytokines may play a
      role.

PMID- 1354522
TI  - Proliferative and differentiative potential of murine yolk sac and fetal stem
      cells.

PMID- 1354523
TI  - HIV-triggered killing of booby trapped cells prevents viral spread in an HIV
      infected cell population.

PMID- 1354524
TI  - Embryonic chimeras and hemopoietic system development.

PMID- 1354525
TI  - Primary immunodeficiencies: molecular aspects and treatment.

PMID- 1354526
TI  - HLA typing by serology and by molecular biology of fetal and cord-blood cells.

PMID- 1354527
TI  - Clinical and biological aspects of human umbilical cord blood as a source of
      transplantable hematopoietic stem and progenitor cells.
AB  - Presented is a short review of the current status fo the clinical and biological
      aspects of using human umbilical cord blood as a source of transplantable
      hematopoietic stem and progenitor cells.

PMID- 1354528
TI  - The SCID-hu mouse: a small animal model for the analysis of human hematolymphoid
      differentiation and function.

PMID- 1354529
TI  - SCID-hu mice as a model to study tolerance after fetal stem cell transplantation.
AB  - SCID-hu mice were constructed with human fetal liver and human fetal thymus,
      obtained from the same or from different donors. Hematopoietic cells originating
      from the fetal liver migrate to the fetal thymus and give rise to medullary and
      cortico-medullary macrophages and dendritic cells. Thymic epithelial cells remain
      of thymic donor origin. The fetal liver donor derived stem cells differentiate in
      this environment into double positive and finally single positive CD4 or CD8
      expressing T cells. The TCR V beta repertoire generated at the double positive
      stage is identical to that generated in the thymus of the donor. Thymic selection
      induces changes in V beta usage comparable to those previously reported for
      normal human thymus. Single-positive, functionally mature, and mainly TCR alpha
      beta+ T cells reach the peripheral blood compartment of the SCID-hu mice. These T
      cells are able of specific proliferative and cytotoxic alloresponses. No
      autoreactivity is observed. Single positive T cells which differentiated in the
      thymus of SCID-hu mice transplanted with liver and thymus of two different donors
      are tolerant to the HLA antigens of both donors. By limiting dilution analysis,
      it could be demonstrated that tolerance to the fetal liver donor is due to clonal
      deletion whereas tolerance to the fetal thymus donor is not. These data show that
      human T cell development is progressing normally in these mice and gives rise to
      a mature, functional and polyclonal T cell repertoire which is comparable to that
      observed in normal individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354530
TI  - Human-ovine xenogenic transplantation of stem cells in utero.
AB  - The preimmune status of the early gestational age fetus provides a permissive
      environment that bypasses the immunological barrier and permits the engraftment
      and expression of hemopoietic stem cells (HSC). We used in utero approach to
      establish long term (greater than 2 years) engraftment and expression of human
      fetal liver HSC in sheep. Engraftment occurred in 40% (13 of 33) of the
      recipients. Of 5 live born sheep, all were chimeric. Engraftment was
      multilineage, involving lymphoid, myeloid and erythroid donor (human) cells.
      Interestingly, these progenitors have continued to exhibit responsiveness to
      human specific growth factors both in vitro and in vivo. Therefore, the
      integration of human HSC into the hemopoietic framework of the host appeared to
      be incomplete, with donor progenitors retaining certain phenotypic
      characteristics that may be exploited to preferentially manipulate the donor
      (human) cell population in these animals. Donor HSC primarily seeded the host
      bone marrow. Since the donor cells were of liver origin and the host liver at the
      time of transplantation was the major hemopoietic organ, this near exclusive
      seeding to the marrow indicates the greater affinity of marrow for the homing
      HSC. Nonetheless, no cells of donor origin appeared in the host circulation until
      the perinatal period, suggesting that donor HSC expand with the developing marrow
      spaces, but do not undergo terminal differentiation. The absence of a significant
      immunological barrier and the availability of expanding marrow homing sites
      render the fetus an excellent host (and donor) for HSC transplantation.

PMID- 1354531
TI  - The child conceived to give life. The point of view of the hematologist.
AB  - The different modalities of stem cell transplantation and the indication of each
      of them are briefly discussed. Transplantation can be successfully applied in
      hematologic diseases or in congenital disorders.

PMID- 1354532
TI  - The child conceived to give life.
AB  - Bone Marrow Transplantation (BMT) demands a living compatible donor. Some parents
      will conceive a child "for BMT". These pregnancies have three main
      characteristics. The traumatic situation of the impending death of a child, the
      inevitable uncertainty of their issue, of BMT results, the intrusion of biology
      into the family dynamics.

PMID- 1354533
TI  - In utero transplantation of stem cells in humans: technical aspects and clinical
      experience during pregnancy.
AB  - Four fetal patients have received fetal liver cell transplants in utero, at the
      fertilization ages of 12-28 weeks. Depending on the age, intraperitoneal
      injection or intravenous infusion into the umbilical vein was used, under
      ultrasonic guidance. In three of the four cases, engraftment has been obtained
      and has resulted in cure or significant improvement of the inherited disease.

PMID- 1354534
TI  - Integrated multimodal therapy of children with attention-deficit hyperactivity
      disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) affects about 3-9% of children in
      the United States. It is a complex, multidetermined ailment that causes profound
      difficulty not only for the children but also for their families and those in the
      broader social environment (e.g., schools). Although medication helps an ADHD
      child's day-to-day functioning, it is less effective in producing long-lasting
      improvement when used alone. The author therefore discusses the rationale and
      techniques for multimodal treatment, including the use of education, cognitive
      behavioral therapy, behavior modification, and structural and dynamic therapy, as
      well as medication. He emphasizes that the use of multiple modalities produces
      therapeutic benefit greater than the sum of each modality's contribution. The
      author's basic premise is that psychodynamic understanding is crucial in
      determining how to combine various therapies and make them mutually facilitative.

PMID- 1354536
TI  - Inhibition by salmeterol of increased vascular permeability and granulocyte
      accumulation in guinea-pig lung and skin.
AB  - 1. The long-acting beta 2-adrenoceptor agonist, salmeterol has been evaluated for
      its anti-inflammatory effects in the guinea-pig lung and skin. 2. Salmeterol,
      administered in bronchodilator doses to conscious guinea-pigs by both oral (0.01
      1.0 mg kg-1) and inhaled (nebulizer concentration, 0.001-1.0 mg ml-1) routes,
      inhibited histamine-induced plasma protein extravasation (PPE) into the airway
      lumen. 3. Inhibition of PPE by salmeterol was long-lasting (greater than 6 h) and
      was inhibited by prior administration of propranolol (1 mg kg-1, s.c.),
      indicating an effect mediated by beta-adrenoceptors. 4. Inhaled salbutamol
      (nebulizer concentration, 0.001-1.0 mg ml-1) also inhibited PPE in guinea-pig
      lung but, in contrast to salmeterol, this effect was short-lived with substantial
      loss of activity 2 h after administration. 5. Inhaled salmeterol (0.1 mg ml-1)
      and salbutamol (1.0 mg ml-1) inhibited the accumulation of neutrophils in guinea
      pig lung in response to lipopolysaccharide (100 micrograms ml-1). Salmeterol, but
      not salbutamol, inhibited the infiltration of eosinophils into the airway lumen
      in response to platelet activating factor (100 micrograms ml-1). These effects of
      salmeterol were blocked by prior administration of propranolol (5 mg kg-1, s.c.),
      indicating that they were also beta-adrenoceptor-mediated. 6. Oral salmeterol (10
      mg kg-1, p.o.), but not salbutamol (10 and 100 mg kg-1, p.o.), inhibited zymosan
      induced granulocyte accumulation and PPE in guinea-pig skin. Lower doses of
      salmeterol (0.1 and 1 mg kg-1) inhibited PPE, but not granulocyte
      accumulation.The effects of salmeterol were blocked by prior administration of
      propranolol (1mgkg-', s.c.). Both salmeterol and salbutamol inhibited histamine
      induced PPE in guinea-pig skin.7. Intradermal salmeterol (10-'mol per site), but
      not salbutamol, was also effective in inhibiting zymosan-induced granulocyte
      accumulation and PPE in guinea-pig skin.8. It is concluded that salmeterol, at
      bronchodilator doses in the guinea-pig, inhibits granulocyte accumulation and
      PPE, possibly by an action on the vasculature. As this profile of activity is not
      shared by the shorter-acting compound, salbutamol, it would seem that anti
      inflammatory activity is associated with beta-adrenoceptor agonism of long
      duration. The implications of these findings for the use of salmeterol in the
      treatment of bronchial asthma are discussed.

PMID- 1354535
TI  - Formoterol and salbutamol inhibit bradykinin- and histamine-induced airway
      microvascular leakage in guinea-pig.
AB  - 1. The effects of the beta 2-adrenoceptor agonists, salbutamol and formoterol, on
      the increase of microvascular permeability induced by histamine or bradykinin in
      guinea-pig airways have been studied in vivo. Extravasation of intravenously
      injected Evans blue dye was used as an index of permeability. The effects of
      salbutamol and formoterol on the increase in pulmonary airway resistance induced
      by histamine or bradykinin have also been studied. 2. The increase in pulmonary
      airway resistance induced by histamine or bradykinin was totally inhibited by
      salbutamol and formoterol. The ED50 of the two mediators were 0.59 +/- 0.21 (n =
      5) and 0.20 +/- 0.14 (n = 5) micrograms kg-1 respectively for salbutamol, and
      0.13 +/- 0.12 (n = 6) and 0.02 +/- 0.01 (n = 6) micrograms kg-1 respectively for
      formoterol. 3. Salbutamol (10 and 30 micrograms kg-1) and formoterol (1 and 10
      micrograms kg-1) inhibited the increase of microvascular permeability induced by
      histamine (30 micrograms kg-1) in the guinea-pig airways. The inhibitory effect
      was predominant in the trachea and the main bronchi, with a maximum inhibition of
      20 to 50%. The two drugs had little or no inhibitory effect on the other
      structures studied, viz. nasal mucosa, larynx, proximal and distal intrapulmonary
      airways. 4. Salbutamol and formoterol (1 and 10 micrograms kg-1) abolished the
      increase in microvascular permeability induced by bradykinin (0.3 micrograms kg
      1). This inhibitory effect of two beta-adrenoceptor stimulants was predominant in
      the trachea and the nasal mucosa where it was observed with 1 microgram kg-1 of
      the beta-adrenoceptor agonists.In the main bronchi, and in the proximal and
      distal intrapulmonary airways, the effects of bradykinin were abolished by 10 pg
      kg- of formoterol and salbutamol.5. The effects of bradykinin, but not those of
      histamine, were significantly reduced (nasal mucosa, main bronchi and distal
      intrapulmonary airways) or abolished (trachea, proximal intrapulmonary airways)
      by morphine 10mgkg-1, i.v. These results suggest that an indirect effect, through
      non-adrenergic noncholinergic (NANC) nerves is involved in the action of
      bradykinin on the microvascular permeability.6. In conclusion, intravenously
      injected beta-adrenoceptor stimulants can inhibit, partially or totally, the
      increase of airways microvascular permeability induced by intravenous histamine
      or bradykinin. However, these effects require doses that are higher than those
      that inhibit the increase in pulmonary airway resistance induced by these
      mediators. As suggested by the results obtained with morphine, the higher
      efficacy of beta2-adrenoceptor agonists versus bradykinin may occur through
      activation of presynaptic receptors of the non-adrenergic non-cholinergic (NANC)
      nerves preventing release of inflammatory neuropeptides such as substance P and
      neurokinin A.

PMID- 1354537
TI  - Evidence for an atypical, or beta 3-adrenoceptor in ferret tracheal epithelium.
AB  - 1. A preparation of the ferret trachea in vitro was used to examine the effects
      of three selective beta-adrenoceptor agonists on lysozyme secretion from
      submucosal gland serous cells and epithelial albumin transport into tracheal
      mucus following sustained, submaximal stimulation of mucus production with
      methacholine (20 microM). 2. Prenalterol, salbutamol and BRL 37344 all enhanced
      methacholine-induced albumin output. BRL 37344 was 10,000 times more potent than
      salbutamol, and salbutamol was slightly more potent than prenalterol. The
      concentrations required to increase albumin output by 100% (EC100%) were 1.4 nM,
      0.7 mM and approximately 1.0 mM for BRL 37344, salbutamol and prenalterol,
      respectively. All three agonists inhibited methacholine-induced lysozyme output,
      with salbutamol being 60 times more potent than BRL 37344, and BRL 37344 being
      approximately 100 times more potent than prenalterol. 3. The selective beta 2
      adrenoceptor antagonist, ICI 118551, inhibited the increase in albumin output
      produced by BRL 37344, but much more potent at inhibiting the response to
      salbutamol; the pA2 for ICI 118551 was 5.55 and 7.18 (P less than 0.001) when the
      agonist was BRL 37344 and salbutamol, respectively. ICI 118551 also attenuated
      the inhibition of lysozyme output produced by the two agonists, but was 10-30
      times more potent at inhibiting this response than the albumin response to BRL
      37344 and salbutamol. 4. The greater potency (4-5 orders of magnitude) of BRL
      37344, compared to the beta 1- (prenalterol) and beta 2- (salbutamol)
      adrenoceptor selective agonists, in stimulating methacholine-induced albumin
      transport suggests that tracheal epithelium possess an atypical, or beta 3
      adrenoceptor similar to that previously reported for adipocytes and
      gastrointestinal smooth muscle. The weak antagonism of the response to BRL 37344
      by ICI 118551 would also be consistent with an atypical adrenoceptor mediating
      the albumin transport response. Inhibition of methacholine-induced serous cell
      lysozyme output would appear to be mediated predominantly by beta2
      adrenoceptors.5. In view of the possible beneficial protective effects of albumin
      in airway surface liquid, selective beta3-agonists like BRL 37344 might have
      potential value in the prevention and/or treatment of inflammatory airway
      disease.

PMID- 1354538
TI  - Alpha-adrenoceptor modulation of the efferent function of capsaicin-sensitive
      sensory neurones in guinea-pig isolated atria.
AB  - 1. Transmural nerve stimulation of guinea-pig atria, obtained from animals
      pretreated with reserpine (5 mg kg-1, i.p.), in the presence of atropine 1 microM
      and of the beta-adrenoceptor blocker CGP 20712A 1 microM, induced a positive
      inotropic effect which was reduced by the calcitonin gene-related peptide (CGRP)
      antagonist hCGRP-(8-37) and abolished by pretreatment with capsaicin 1 microM. 2.
      Noradrenaline concentration-dependently (0.01-10 microM) reduced the increase in
      cardiac contractility induced by transmural nerve stimulation. The inhibitory
      effect of noradrenaline was antagonized by yohimbine (0.5-1 microM), in a dose
      dependent manner. Prazosin (0.5-1 microM) antagonized the effect of noradrenaline
      and this effect was independent of concentration. 3. In the presence of
      yohimbine, the lower part of the inhibitory-response curve for noradrenaline was
      slightly but significantly shifted by prazosin. A similar degree of antagonism
      was observed in the presence of 1 microM phenoxybenzamine. 4. The selective alpha
      2 agonists BHT 920 and clonidine reduced, in the same concentration-range (0.01-1
      microM), the cardiac response to transmural nerve stimulation in a yohimbine
      sensitive fashion. 5. Phenylephrine (0.1-100 microM) and methoxamine (1-300
      microM) also induced an inhibitory effect on transmural nerve stimulation. The
      effect of phenylephrine was antagonized by yohimbine (1 microM) more efficiently
      than by prazosin (0.5 microM). 6. These results are in keeping with the presence
      of inhibitory prejunctional alpha 2-adrenoceptors on cardiac sensory nerve
      endings which modulate the efferent function of capsaicin-sensitive neurones.

PMID- 1354539
TI  - Cardiovascular actions of a new selective postjunctional alpha-adrenoceptor
      antagonist, SK&F 104856, in normotensive and hypertensive dogs.
AB  - 1. SK&F 104856 (2-vinyl-7-chloro-3,4,5,6-tetrahydro-4-
      methylthieno[4,3,2ef][3]benzazepine) is a novel postjunctional alpha 1- and alpha
      2-adrenoceptor antagonist. 2. SK&F 104856 as well as prazosin and SK&F 86466
      reduced blood pressure in the anaesthetized normotensive dog. 3. SK&F 86466 and
      rauwolscine but not SK&F 104856 or prazosin, produced a marked increase in
      myocardial contractility which corresponds with their ability to block
      prejunctional alpha 2-adrenoceptors. 4. Intravenous or oral administration of
      SK&F 104856 resulted in dose-dependent antihypertensive responses in 1-kidney, 1
      clip (1-K, 1-C) Goldblatt hypertensive dogs with baseline blood pressure of
      approximately 140 mmHg. At 0.1 and 1 mg kg-1, i.v., mean arterial blood pressure
      fell by 11 +/- 5 and 23 +/- 5 mmHg, respectively. At 3 and 10 mg kg-1, p.o.,
      blood pressure fell by 9 +/- 3 and 22 +/- 5 mmHg, respectively. At 10 mg kg-1,
      p.o., the antihypertensive effect of SK&F 104856 was still evident at 4 h. 5. The
      data indicate that SK&F 104856 shows selectivity in vivo for postjunctional
      versus prejunctional alpha-adrenoceptors and is a potent and long-acting
      antihypertensive agent in 1-K, 1-C Goldblatt hypertensive dogs.

PMID- 1354540
TI  - Effects of peptidase inhibition on angiotensin receptor agonist and antagonist
      potency in rabbit isolated thoracic aorta.
AB  - 1. Experiments were performed with peptidase inhibitors on rabbit aortic strip
      preparations, to determine whether endogenous peptidase activity can influence
      the potency estimates for angiotensin receptor agonists and antagonists in this
      tissue. 2. Angiotensin II (A II) and angiotensin III (A III) both induced
      concentration-related contractions of rabbit aortic strip preparations. A III was
      approximately 38 fold less potent than A II, and the gradient of the A III
      concentration-response curve (1.00 +/- 0.04) was significantly more shallow than
      that (1.76 +/- 0.05) of the A II curve. 3. Neither the aminopeptidase-A and -M
      inhibitor, amastatin, nor the aminopeptidase-B and -M inhibitor, bestatin,
      affected the potency of, or the maximum response to, A II. In contrast, the
      potency of A III was increased by both amastatin and bestatin. Amastatin had the
      most marked effect and at 10 microM caused approximately a 12 fold increase in
      the potency of A III (EC50 values, 102 nM and 8.6 nM in the absence and presence
      of amastatin, respectively), and also significantly steepened the gradient of the
      A III concentration-response curve. Amastatin did not affect the position or
      shape of the concentration-response curve to the alpha 1-adrenoceptor agonist,
      phenylephrine. Finally, the carboxypeptidase-N inhibitor, D-L-mercaptomethyl-3
      guanidine-ethylpropanoic acid (MERGETPA) did not change the position or shape of
      the concentration-response curves to either A II or A III.4. In the presence of
      amastatin, the potency of the peptide angiotensin receptor antagonist, Ile7-A III
      (100nM-l microM ), was increased approximately 13 fold (pA2, with A II as the
      agonist, 7.0 +/- 0.1 and 8.1 +/- 0.1, in the absence and presence of amastatin,
      respectively). However, the potency of the nonpeptide angiotensin receptor
      antagonist, DuP 753 (30-300 nM), was little affected by amastatin (pA2, 8.2 +/-
      0.1 and 8.1 +/- 0.1 in the absence and presence of amastatin, respectively).5.
      The results of this study suggest that endogenous aminopeptidase activity in the
      rabbit thoracic aorta can profoundly affect estimates of the potency of peptide
      angiotensin receptor agonists and antagonists.A suitable aminopeptidase inhibitor
      should therefore be included in studies, using this tissue, which aim to classify
      angiotensin receptor subtype(s) based on the rank order of peptide angiotensin
      receptor agonist and/or antagonist potencies.

PMID- 1354541
TI  - Manifestations of acute opiate withdrawal contracture in rabbit jejunum after mu
      , kappa- and delta-receptor agonist exposure.
AB  - 1. Following a 5 min in vitro exposure to morphine (1.3 x 10(-7) M), U-50,488H
      (2.5 x 10(-8) M) and deltorphin (1.6 x 10(-8)-6.5 x 10(-9) M), the rabbit
      isolated jejunum exhibited a precipitated contracture after the addition of
      naloxone (2.75 x 10(-7) M). 2. The precipitated responses to U-50,488H and
      deltorphin but not to morphine were reproducible in the same tissue. 3. The
      precipitated contractures were blocked completely by tetrodotoxin (3 x 10(-7) M),
      partially by atropine (1.5 x 10(-7) M) and not affected by hexamethonium (1.4 x
      10(-5) M). 4. Naloxone administration (2.75 x 10(-7) M) before the agonist
      prevented the development of the adaptive response to morphine and U-50,488H but
      not to deltorphin. 5. The selective antagonists norbinaltorphimine (2.7 x 10(-8)
      2.7 x 10(-9) M) and naltrindole (1.1 x 10(-7) M) prevented the adaptive response
      development only to the respective agonists. 6. The opioid agonists partially
      inhibited the spontaneous activity of the tissue. This study has shown that
      independent activation of mu-, kappa- and delta-opioid receptors can induce
      dependence in this isolated tissue. Rabbit jejunum is a suitable tissue for
      studying the acute effects of opioids on the adaptative processes determined by
      their administration.

PMID- 1354542
TI  - Beta-adrenoceptor agonist stimulation of acid secretion by rat stomach in vitro
      is mediated by 'atypical' beta-adrenoceptors.
AB  - 1. A previous study showed beta-adrenoceptor agonists stimulated acid secretion
      by rat stomach in vitro. The receptors could not be classed as either the beta 1-
      or beta 2-subtype. This study examines the effect of 2 'atypical' beta-agonists
      on acid secretion. 2. Basal and isoprenaline-stimulated acid secretion were
      compared in tissues bathed either in HEPES/O2- or HCO3-/CO2-buffer. Basal
      secretion was underestimated in HCO3- by an amount equal to the rate of base
      section. Tissues responded well in HEPES buffer and there was no base secretion
      following acid inhibition with SCH 28080. HEPES was used for the study. 3. SR
      58611A stimulated acid in a concentration-related way (0.1-5 microM). Maximum
      response at 1 microM was equal to the response to a maximal concentration of
      isoprenaline. BRL 37344 (1 microM) also stimulated to the same extent. 4.
      Responses to isoprenaline (5 microM) and SR 58611A (1 microM) were reduced by
      propranolol (10 microM) but not by alprenolol (10 microM) or by practolol (12.5
      microM) plus ICI 118551 (1 microM). 5. Exposure to SR 58611A (1 microM) led to
      desensitization to isoprenaline but not to bethanechol (1 microM) or histamine
      (50 microM). 6. We conclude that a HEPES/O2-buffer is advantageous when measuring
      gastric acid secretion in vitro and the stimulatory effect of beta-adrenoceptor
      agonists is mediated by 'atypical' receptors.

PMID- 1354543
TI  - The non-adrenergic, non-cholinergic response counteracts changes in guinea-pig
      airway tone with and without sympathetic activation.
AB  - 1. We examined whether the non-adrenergic, non-cholinergic (NANC) neural response
      can counteract changes in smooth-muscle tone with and without simultaneous
      sympathetic activation in guinea-pig airways. 2. Isolated airway preparations
      were pretreated with indomethacin (10 microM) and incubated with either atropine
      (1 microM) and guanethidine (10 microM) or atropine (1 microM) alone. The
      response to electrical field stimulation (EFS: 1200 mA, 0.5 ms, 3 Hz for 240 s)
      was studied at various levels of tone prior to EFS: first without induced tone,
      then at a moderate tone induced by histamine (0.3 microM) and finally at a high
      tone induced by histamine (6 microM). 3. The response to EFS was a contraction
      when the tone prior to EFS was low and a relaxation when the tone prior to EFS
      was high. These responses converged towards a similar level of tone, in the
      distal trachea and in the main bronchus, with and without guanethidine. 4. The
      mean (s.e. mean) level of tone towards which the responses to EFS converged was
      lower after incubation with atropine alone compared with incubation with atropine
      and guanethidine, both in the distal trachea [8 (1)% compared with 30 (6)% of
      maximum tone] and in the main bronchus [28 (4)% compared with 57 (2)% of maximum
      tone]. In separate experiments, the guanethidine-induced effect on the responses
      to EFS was imitated by propranolol (1 microM) but not by prazosin (0.3 microM)
      and yohimbine (1 microM). 5. These findings indicate that the NANC neural
      response can counteract changes in airway smooth-muscle tone via a contraction or
      via a relaxation, depending on the tone prior to activation.This stabilizing
      effect on tone does not appear to depend upon adrenergic activation per se. The
      level of tone towards which the NANC responses converge can, however, be reduced
      by beta-adrenoceptor activation, thus suggesting an interaction which provides
      protection from severe airway smooth-muscle contraction.

PMID- 1354544
TI  - Release of endogenous adenosine and its metabolites by the activation of NMDA
      receptors in the rat hippocampus in vivo.
AB  - 1. The effects of N-methyl-D-aspartate (NMDA), KCl, and veratridine on the
      release of endogenous adenosine and its metabolites, inosine and hypoxanthine,
      from the rat hippocampus have been studied by in vivo microdialysis. 2. In the
      hippocampus of rats anaesthetized with urethane the adenosine level reached a
      stable state estimated at 0.93 microM during the first 2 h after the implantation
      of the dialysis probe. NMDA (50 microM to 25 mM) in the perfusate evoked a
      concentration-dependent release of adenosine, inosine and hypoxanthine with an
      EC50 of 180 microM. The release was reduced by 93% by the specific NMDA receptor
      antagonist 2-amino-5-phosphonopentanoic acid (2-AP5) at 200 microM, indicating an
      NMDA receptor-mediated process. In addition, the 100 mM KCl-evoked release of
      adenosine was also substantially reduced by 77% by 2-AP5, suggesting that a large
      component of the K(+)-evoked release is NMDA-receptor-mediated. 3. Perfusion with
      zero-Ca2+ artificial cerebrospinal fluid attenuated the NMDA-evoked release of
      adenosine only by 16% (not significant) but depressed the K(+)-evoked release by
      62%, indicating that most of the NMDA-evoked release is directly receptor
      mediated, whereas a large component of the K(+)-evoked release could be via the
      release of an excitatory amino acid acting at the NMDA receptors.

PMID- 1354545
TI  - Characterization of muscarinic receptors that mediate contraction of guinea-pig
      isolated trachea to choline esters: effect of removing epithelium.
AB  - 1. The muscarinic receptor subtype that mediates contraction of guinea-pig
      trachea, in the presence and absence of epithelium, to acetic and carbamic acid
      choline esters was determined by use of preferential muscarinic receptor
      antagonists: pirenzepine (M1 receptor), methoctramine (M2 receptor) and 4
      diphenylacetoxy-N-methylpiperidine (4-DAMP) (M3 receptor). 2. Acetylcholine
      (ACh), methacholine (MeCh), carbachol (CCh), bethanechol (BeCh) and oxotremorine
      induced concentration-dependent contraction of guinea-pig isolated tracheal
      strips in the presence and absence of epithelium. Contraction to acetic choline
      esters (ACh and MeCh) was augmented by removal of the epithelium, whereas
      contraction to carbamic acid choline esters (CCh and BeCh) and oxotremorine was
      not influenced by removal of the epithelium. 3. Pirenzepine, methoctramine and 4
      DAMP caused parallel rightward displacements of the concentration-contraction
      curves to the muscarinic agonists. The pA2 values (determined from Arunlakshana
      Schild graphs) for pirenzepine and 4-DAMP in guinea-pig trachea in the presence
      of epithelium were: ACh as the agonist, 7.6 and 9.0, respectively; CCh as the
      agonist, 7.6 and 9.1, respectively. The apparent pKB values for methoctramine
      with the same system were: ACh as the agonist, 5.6; CCh as the agonist, 5.6.
      Similar values were obtained with MeCh, BeCh and oxotremorine as the agonists.
      These values were agonist- and epithelium-independent. 4. It is concluded from
      the pA2 and apparent pKB values obtained for the muscarinic receptor antagonists
      used in this study that contraction of guinea-pig isolated trachea, with and
      without epithelium, to both acetic and carbamic acid choline esters is mediated
      via the muscarinic M3 receptor subtype.Differential contractile responses of
      guinea-pig trachea to acetic and carbamic acid choline esters upon the mechanical
      removal of the epithelium may not be explained by activation of different
      muscarinic receptor subtypes by these agonists.

PMID- 1354546
TI  - Cooling and response to adrenoceptor agonists of rabbit ear and femoral artery:
      role of the endothelium.
AB  - 1. The effects of cooling on the response of the rabbit central ear (cutaneous)
      and femoral (non-cutaneous) arteries to stimulation of adrenoceptors and the role
      of the endothelium in these effects, were studied in 2 mm long cylindrical
      segments. 2. Concentration-response curves for noradrenaline (10(-9)-3 x 10(-4)
      M), phenylephrine (alpha 1-adrenoceptor agonist, 10(-9)-3 x 10(-4) M) and B-HT
      920 (alpha 2-adrenoceptor agonist, 10(-7)-10(-3) M) were recorded isometrically
      in arteries with and without endothelium at 37 degrees C and at 24 degrees C
      (cooling). To analyze further the endothelial mechanisms in the responses to
      adrenoceptor stimulation during cooling, the effects of the adrenoceptor agonists
      on ear arteries in the presence of NG-nitro-L-arginine methyl esther (L-NAME)
      (10(-5) M) were also determined. 3. In every condition tested, the three
      adrenoceptor agonists produced a concentration-dependent arterial contraction and
      the order of potency in ear and femoral arteries was noradrenaline greater than
      or equal to phenylephrine greater than B-HT 920. The response of ear and femoral
      arteries to phenylephrine or B-HT 920 was blocked by prazosin (10(-6) M).
      Yohimbine (10(-6) M) decreased slightly the response of ear arteries and
      increased that of femoral arteries to B-HT 920. 4. The sensitivity of both ear
      and femoral arteries to the three adrenoceptor agonists was significantly lower
      at 24 degrees C than at 37 degrees C. 5. In ear arteries, endothelium removal or
      treatment with L-NAME did not influence the response at 37 degrees C, but did
      increase it during cooling to adrenoceptor stimulation.In femoral arteries,
      endothelium removal increased the sensitivity to noradrenaline and, especially,
      to B-HT 920 at 37 degrees C, but did not affect the response at 24 degrees C.6.
      The results suggest that: (a) rabbit ear and femoral arteries are equipped mainly
      with alpha 1-adrenoceptors;(b) at 37 degrees C, the contraction of the ear artery
      to adrenoceptor agonists is mostly endothelium-independent, and in the femoral
      artery the contraction to alpha 2-adrenoceptor activation is endothelium
      dependent; (c) cooling inhibits the contraction to adrenoceptor agonists in both
      ear and femoral arteries: in the ear artery probably by increasing the
      availability of endothelial nitric oxide, but in the femoral artery by depressing
      the sensitivity of alpha-adrenoceptors in the smooth musculature.7. The results
      suggest that the endothelium may modulate the adrenoceptor response of cutaneous
      arteries during changes in temperature.

PMID- 1354547
TI  - Selective reduction of glutamate in the rat superior colliculus and dorsal
      lateral geniculate nucleus after contralateral enucleation.
AB  - The effects of afferent lesions on the levels of glutamate, aspartate and gamma
      aminobutyric acid (GABA) in the laminae of the superior colliculus (SC) and
      dorsal lateral geniculate nucleus (dLGN) of the rat were studied, using
      microassay methods for these amino acids. The analysis was performed 12-14 days
      after left eye enucleation, or ablation of right visual cortical area, or both
      left eye enucleation and ablation of right visual cortex. Superficial gray layer
      (SGL) and deep layers in the SC were dissected out from the thin-sectioned,
      freeze-dried sample. In the dLGN, the outer and inner laminae were separately
      dissected. The glutamate contents in the upper half of SGL and outer lamina of
      dLGN contralateral to eye enucleation decreased significantly (15%). Combination
      of eye enucleation and visual cortical ablation further decreased the glutamate
      content in the upper half of the right SGL (29.3%). On the other hand, aspartate
      and GABA concentrations in the SC and dLGN exhibited no significant reduction
      after deafferentations. These results indicate that the retino-tectal and retino
      geniculate pathway of the rat may be glutamatergic in nature.

PMID- 1354548
TI  - Somatostatin receptors in the human cerebellum during development.
AB  - The ontogeny of somatostatin receptors (SRIF-R) was studied in the human
      cerebellum from mid-gestation to the 15th month postnatal. The brains were
      collected 3-26 h after death, from 18 fetuses and infants, and from 4 adults aged
      from 48 to 82. SRIF-R were characterized by membrane-binding assay and their
      localization was determined by in vitro autoradiography. Both techniques were
      conducted with two radio-ligands: [125I-Tyr0, DTrp8]S14 and D-Phe-Cys-125I-Tyr
      DTrp-Lys-Thr- ol (125I-SMS 204-090). Membrane-binding studies carried out with
      each radioligand showed the presence of a single population of saturable, high
      affinity binding sites. Neither were the Kd values for either ligand (assessed by
      Scatchard analysis) changed appreciably during development, mean Kd values being
      0.36 +/- 0.04 nM and 0.56 +/- 0.11 nM for [125I-Tyr0,DTrp8]S14 and 125I-SMS 204
      090, respectively. Although inter-individual fluctuations of the Bmax were
      observed, the concentration of SRIF-R in the cerebellum of fetuses and infants up
      to 8 months appeared to be at least 2- to 10-fold higher than in the adult
      cerebellum. No appreciable differences in the Bmax values were found using either
      radioligand. The highest density of SRIF-R was observed in the cerebellar cortex
      of fetuses, in particular in the external granule cell layer (EGC), where stem
      cells of the granule cells are generated and enter the differentiation process. A
      high density of SRIF-R also occurred in the internal granule cell layer.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1354549
TI  - Deficits in the somatostatin SS1 receptor sub-type in frontal and temporal
      cortices in Alzheimer's disease.
AB  - The aim of this study was to evaluate the possible differential alterations of
      somatostatin (SRIF) receptor sub-types in Alzheimer's disease (AD). Consequently
      the binding profile of cortical SRIF receptors were examined in normal and AD
      brains using non-selective ([125I]Tyr0, D-Trp8-SRIF14) and SS1 receptor sub-type
      selective ([125I]SMS204-090) radioligands. Maximal binding capacities, but not
      affinities, were reduced for both ligands in the temporal cortex. In contrast,
      only the maximal binding capacity of [125I]SMS204-090 was significantly reduced
      (68%) in the frontal cortex; no alterations were detected using the non-selective
      probe. This reveals that while the maximal binding capacity of the SS1 receptor
      sub-type is altered in frontal and temporal cortices in AD, other putative
      cortical SRIF receptor classes (such as SS2 sites) are not as broadly affected.
      This could be of significance for eventual therapeutic approaches using SRIF
      related analogues.

PMID- 1354550
TI  - NBQX, an AMPA antagonist, reduces glutamate-mediated brain edema.
AB  - Glutamate (2.5 mg) was administered after the blood-brain barrier had been opened
      by a unilateral intracarotid infusion of 5 mg protamine sulfate in rats. Whereas
      the brain specific gravity, measured 24 h later, did not differ between the
      injected and non-injected side after protamine alone, glutamate significantly
      reduced the specific gravity in the right hemisphere indicating brain edema (P
      less than 0.01). NBQX, a potent AMPA receptor antagonist, significantly reduced
      the edema (P less than 0.01) and completely inhibited the glutamate mediated
      increase in albumin content in cerebrospinal fluid (P less than 0.01).

PMID- 1354551
TI  - In vivo microdialysis of amino acid neurotransmitters in the hippocampus in
      amygdaloid kindled rat.
AB  - Extracellular concentrations of gamma-aminobutyric acid (GABA), glutamate (Glu)
      and aspartate (Asp) were determined by microdialysis in rat hippocampus during
      various amygdaloid kindled stages. The values of GABA and Glu were increased 3-4
      times in C2-C3 stages in comparison with the values in control animals. After
      reaching the C5 stages, these values were increased 3-7 times. However, the
      concentration of Asp decreased depending on the kindling stage, reaching the
      lowest value of 33% in comparison with the normal value. The observed changes may
      be related to kindling induced seizures.

PMID- 1354552
TI  - G proteins are involved in the regulation of transmitter release at an Aplysia
      cholinergic synapse.
AB  - At an identified cholinergic synapse of the Aplysia buccal ganglion, presynaptic
      injections of guanosine 5'-O-3-thiotriphosphate (GTP-gamma-S) depressed the
      amplitude of evoked postsynaptic responses. This reduction of acetylcholine (ACh)
      release by GTP-gamma-S, prevented by pre-injection of guanosine 5'-O-2
      thiodiphosphate (GDP-beta-S) in the presynaptic neuron, was due to a reduction of
      the number of ACh quanta released. The mean amplitude of the evoked miniature
      postsynaptic current (MPSC) was unchanged. The presynaptic Ca2+ influx was
      lowered.

PMID- 1354553
TI  - Potassium-induced long-term potentiation in rat hippocampal slices.
AB  - We observed that a transient increase in extracellular potassium concentration
      (50 mM for 40 s) was sufficient to induce long-term potentiation (LTP) of
      synaptic transmission in area CA1 of the hippocampal slice. Potassium-induced
      potentiation of the Schaffer collateral/commissural synapses demonstrated several
      features characteristic of tetanus-induced LTP: (1) population excitatory post
      synaptic potential (EPSP) amplitudes were enhanced to a similar magnitude (on
      average 70% above baseline) which (2) lasted for more than 20 min; (3) induction
      was blocked by bath application of the specific N-methyl-D-aspartate (NMDA)
      receptor antagonist D-2-amino-5-phosphonovalerate (D-APV), and (4) was attenuated
      by reduction of the concentration of calcium in the extracellular medium.
      Induction of either potassium-induced LTP or tetanus-induced LTP occluded the
      subsequent expression of the other. Finally, exposure to high potassium in the
      absence of electrical stimulation was sufficient to induce LTP. Taken together,
      these data indicate that brief depolarizing stimuli other than tetanus can induce
      LTP. Because potassium-induced LTP is not restricted to the subset of afferents
      examined electrophysiologically, such a method could facilitate analyses of the
      biochemical events underlying both the induction and expression of LTP.

PMID- 1354554
TI  - The effect of glutamate antagonists on c-fos expression induced in spinal neurons
      by irritation of the lower urinary tract.
AB  - Chemical irritation of the lower urinary tract (LUT) of the rat increases the
      expression of c-fos in neurons in the dorsal horn, dorsal commissure and
      intermediolateral region of the spinal cord. The role of glutamatergic synapses
      in this response was examined using two glutamate receptor antagonists, MK-801
      (an NMDA antagonist) and CNQX (an AMPA antagonist). In rats with an intact spinal
      cord, MK-801 (3.5 mg/kg, i.v.) administered 15 min before bladder irritation
      decreased (50-60%) the number of c-fos-positive cells in all regions of the cord.
      A smaller dose of MK-801 (0.8 mg/kg, i.v.) was ineffective. In spinal transected
      rats (4-7 days prior to the experiment) MK-801 (3.5 mg/kg, i.v.) decreased c-fos
      expression only in the medial dorsal horn. CNQX (1.2 mg/kg, i.v.) was ineffective
      in both preparations. These results indicate that activation of NMDA receptors at
      glutamate synapses in the central nervous system may play a role in the
      processing of nociceptive input from the LUT and may also be involved in reflex
      pathways mediating micturition.

PMID- 1354555
TI  - Asymmetric elevation of striatal dopamine D2 receptors in the chakragati mouse:
      neurobehavioral dysfunction in a transgenic insertional mutant.
AB  - We have previously reported the discovery of a transgenic insertional mutant,
      recently named the chakragati (ckr) mouse, which displays lateralized circling,
      locomotor hyperactivity, hyperreactivity, as well as body weight deficits. Since
      lateralized dopamine function is associated with circling behavior we sought to
      determine whether dopamine (DA) D1 and D2 receptors were asymmetrically
      distributed in the striata of adolescent and adult ckr mice using receptor
      autoradiography. Stereotypic and rotational responses to quinpirole served as
      behavioral indices of D2 receptor function. The ckr mice showed hemispherically
      asymmetric elevations in DA D2 receptors in the lateral subregions of the
      striatum whereas medial regions of the striatum were symmetrically and
      bilaterally elevated (overall elevation = 30%). As a group, ckr mice had higher
      D2 receptor levels on the side which was contralateral to the preferred direction
      of spontaneous nocturnal rotation. Striatal D1 receptors and mesolimbic D2 and D1
      receptors of ckr mice were neither elevated nor differentially asymmetric. Young
      adult ckr mice showed dose-dependent increases in net rotations in response to
      quinpirole whereas normal mice showed no change from baseline levels. Both groups
      showed similar stereotypic responses. Older adult ckr mice, however, showed dose
      dependent reductions in rotation after quinpirole whereas normal mice turned at
      baseline levels. Older ckr mice also displayed significantly greater stereotyped
      sniffing behavior. This unique mutant provides a novel genetic model of basal
      ganglia dysfunction, and may be useful in studying aspects of neuropsychiatric
      disorders associated with dopaminergic abnormalities.

PMID- 1354556
TI  - Comparison of neuroendocrine and behavioral effects of ipsapirone, a 5-HT1A
      agonist, in three stress paradigms: immobilization, forced swim and conditioned
      fear.
AB  - Ipsapirone is an anxiolytic drug and a serotonin1A (5-HT1A) agonist. The aim of
      the present study was to investigate the effects of low doses of ipsapirone on
      the hormonal and behavioral response to three stress procedures: immobilization,
      forced swim and conditioned emotional response (CER). We examined the effect of
      ipsapirone (0.1, 0.5 or 1.0 mg/kg) on plasma renin concentration (PRC), adrenal
      corticotropic hormone (ACTH), corticosterone, prolactin and defecation in rats
      exposed to immobilization, forced swim or CER stress. All three stressors
      significantly elevated all the hormone levels (P less than 0.01). Immobilization
      induced elevations of PRC, and corticosterone were inhibited by the highest doses
      of ipsapirone (0.5 and 1 mg/kg, i.p.). However, ipsapirone did not modify the
      immobilization-induced elevations of plasma ACTH, prolactin or defecation.
      Ipsapirone was relatively ineffective at reducing the endocrine responses to
      forced swim. Ipsapirone reduced some, but not all of the hormonal responses to
      CER stress. CER-induced elevations of corticosterone and prolactin were not
      inhibited by ipsapirone. However, the ACTH response to CER was significantly (P
      less than 0.01) inhibited by all doses of ipsapirone and the highest dose of
      ipsapirone attenuated the renin response. In contrast with the hormonal
      responses, ipsapirone inhibited all of the behavioral responses to CER stress.
      Ipsapirone inhibited CER-induced freezing behavior and defecation, while dose
      dependently reversing the suppressive effect of CER on exploring, grooming and
      rearing behaviors. In conclusion, there is a dissociation between the influence
      of ipsapirone on the endocrine and behavioral responses to CER stress. Ipsapirone
      also has differential effects on the neuroendocrine response to the three
      stressors studied. Ipsapirone was most effective in attenuating the hormonal
      responses to CER, followed by immobilization and swim stress. Of the hormones
      studied, the stimulation of renin secretion after exposure to the three stressors
      was most sensitive to ipsapirone, while corticosterone and prolactin were the
      least sensitive to ipsapirone.

PMID- 1354557
TI  - Dynorphin A-(1-17) and dynorphin B are released from in vitro superfused rat
      hypothalami. Effects of depolarizing agents and ovariectomy.
AB  - We measured the release of immunoreactive (ir) dynorphin (dyn) A-(1-17) and dyn B
      from the rat hypothalamus by an in vitro superfusion technique. The system was
      validated on the basis of the recovery and stability of radiolabeled peptides
      added to the superfused hypothalami. These were detected as authentic peptides by
      reverse-phase high-performance liquid chromatography (rp-HPLC) only in the
      presence of a cocktail of peptidase inhibitors added to the superfusion medium.
      We observed spontaneous release of ir-dyn B, evaluated by a validated
      radioimmunoassay in the superfusates, that was increased by potassium and
      veratridine depolarization. It was calcium-dependent and tetrodotoxin-sensitive.
      We could not evaluate ir-dyn A-(1-17) directly in the superfusates, because the
      peptidase inhibitors added to the medium significantly altered the tracer
      antibody reaction. To obviate this problem, pooled superfusate samples were
      purified on C18 cartridges and assayed by rp-HPLC. Rp-HPLC analysis of
      superfusates revealed two molecular forms with the same retention time as
      authentic dyn A-(1-17) and dyn B which were four times higher in K(+)-stimulated
      fractions. We could not detect dyn A-(1-32), comprising dyn A-(1-17) and dyn B,
      even though this peptide is recognized by the antibodies used in this study and
      is detected in acetic acid extracts of the rat hypothalamus. The spontaneous and
      K(+)-evoked release of ir-dyn A-(1-17) and ir-dyn B were significantly higher in
      2-week ovariectomized rats, in parallel with the increase of their content in the
      anterior hypothalamus preoptic area.

PMID- 1354558
TI  - Action potentials produce a long-term enhancement of M-current in frog
      sympathetic ganglion.
AB  - M-current is a voltage-gated K+ current that can be turned off by the muscarinic
      action of acetylcholine. We examined the effects of postsynaptic action potential
      firing on the level of M-current in B-cells of the bullfrog sympathetic ganglion.
      High frequency stimulation of action potentials induced an approximately two-fold
      increase in the level of the M-current that could last up to 35 min. The
      'enhanced' M-current was similar to the 'resting' one in its time-dependence,
      voltage-dependence and sensitivity to neurotransmitters. Experiments were
      undertaken to examine the functional consequences of the enhanced M-current.
      Following high frequency stimulation the number of spikes evoked by depolarizing
      current was reduced. In addition, the excitatory postsynaptic potential (EPSP)
      evoked by maximal input became subthreshold, thereby blocking information flow
      through the ganglion cell. These results indicate that the enhancement of M
      current by spikes provides a negative feedback mechanism for the control of
      excitability. It has been reported that postsynaptic stimulation of ganglion
      cells also produces a long-term increase in the nicotinic EPSP, but we were
      unable to confirm this observation.

PMID- 1354559
TI  - Insulin-specific sensitization of cultured cerebrocortical neurons to glutamate
      excitotoxicity.
AB  - The effect of insulin on the sensitivity of neurons to excitatory amino acid
      induced cytotoxic cell death was examined in primary cultures of the rat cerebral
      cortex. Cells developed for two weeks in serum supplemented medium in the
      presence or absence of insulin, insulin-like growth factor or b-fibroblast growth
      factor. Excitotoxic cell death was induced by 1 mmol/l glutamate, N-methyl-D
      aspartate, kainate or quisqualate. The vulnerability of cells was evaluated by
      the measurement of lactate dehydrogenase release due to cytotoxic injury. In
      contrast to the moderate evaluation of protein content by all the 3 growth
      factors, only insulin increased the vulnerability of cells to the neurotoxic
      effects of glutamate and of the 3 excitatory amino acid receptor agonists
      examined. Our results show that the induction of vulnerability in cortical
      cultures is a specific action of insulin and not a general effect of growth
      factors. Moreover, the increased vulnerability to N-methyl-D-aspartate,
      quisqualate and kainate suggests that the effect of insulin is exerted through
      intracellular mechanisms other than a selective induction of one subpopulation of
      excitatory amino acid receptors.

PMID- 1354560
TI  - Glutamate selectively increases the high-threshold Ca2+ channel current in
      sensory and hippocampal neurons.
AB  - Previous studies resulted in conflicting conclusions that glutamate application
      either decreases or increases the activity of Ca2+ channels in hippocampal
      neurons. We studied whole-cell Ca2+ currents (ICa) in chick dorsal root ganglion
      neurons and rat hippocampal cells. For both cell types glutamate (1-30 microM)
      increased high-threshold Ca2+ current. It was independent of the charge carriers,
      Ca2+ or Ba2+. Low-threshold Ca2+ channel current and the fast sodium current were
      not changed with glutamate application. The effect developed within 1-2 min and
      then further facilitated after washout of the agonist. A second application of
      glutamate produced no additional increase in ICa. No changes in the time-course
      of whole-cell currents were observed, suggesting that glutamate recruits 'sleepy'
      Ca2+ channels. Whatever its mechanism, overlasting increase of ICa by glutamate
      may be important in neuronal plasticity.

PMID- 1354561
TI  - Presumptive adrenergic neurons containing phenylethanolamine N-methyltransferase
      immunoreactivity in the medulla oblongata of neonatal swine.
AB  - Given the importance of the swine (Sus scrofa) as an animal model for human
      development, physiology and disease, neurons containing the epinephrine
      synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT), were mapped
      in the medulla oblongata of neonatal swine as a first step in identifying their
      roles in central autonomic control. Neurons were labeled immunocytochemically by
      using an antiserum to PNMT raised in rabbits against trypsin-treated enzyme
      purified from the bovine adrenal gland. The general regional organization of
      neurons expressing PNMT (-like) immunoreactivity (ir) in the neonatal swine was
      similar to data obtained in other species and, in some aspects, more closely
      resembled the pattern observed in the primate brain. Immunolabeled cells appeared
      to be more abundant and caudally more extensive than observed in other adult
      animals. PNMT-immunoreactive (ir) neuronal somata, however, were largely confined
      to the reticular formation in the ventrolateral quadrant and the nucleus tractus
      solitarii (NTS) and more restricted in distribution than those expressing
      tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (D beta H)-ir on serial
      transverse sections. A close correspondence was observed between the
      distributions of TH- and PNMT-ir neurons and processes throughout the C1 and C2
      areas. However, in the C1 and C3 regions TH-ir neurons outnumbered those
      containing D beta H and PNMT-ir. In contrast, cell groups enriched in PNMT-ir
      neurons and processes were characterized by relatively weak D beta H-ir. In the
      ventrolateral medulla (VLM), PNMT-ir cell bodies were concentrated rostrally and
      extended from the caudal pole of the facial nucleus to a level posterior to the
      calamus scriptorius. The rostral VLM was characterized by an admixture of bipolar
      and multipolar primarily medium-diameter immunostained neurons. A prominent cell
      column (condensation) organized ventromedially to the nucleus ambiguus pars
      compactus (NAc). A loosely organized cluster bordered the lateral aspect of the
      special visceral efferent column; another smaller aggregate was located in the
      ventromedial reticular formation adjacent to the inferior olive. At middle
      medullary levels, PNMT-ir neurons formed two distinct subgroups (dorsal and
      ventral) interrupted by a band of precerebellar relay neurons that extended
      between the medial and lateral limbs of the lateral reticular nucleus of Walberg.
      At obex, the dorsal cell group formed a diagonal array and assumed a position
      dorsal and dorsolateral to the medial limb of LRN. This group was distinguished
      by bipolar neurons with axes of orientation directed perpendicularly to the
      majority of neurons in the rostal VLM or those lying near the caudal
      ventromedullary surface.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1354562
TI  - The effect of hypoxia on neurotransmitter phenotype of forebrain cholinergic
      neurons.
AB  - The effect of hypoxia on the neurotransmitter phenotype of rat forebrain
      cholinergic neurons was analyzed using a dissociated fetal rat culture system.
      The aims of this study were to examine the feasibility of using choline
      acetyltransferase (ChAT) activity as a measure of cell injury and/or recovery, to
      measure the time course of hypoxic effects on ChAT activity, to determine how
      changes in ChAT activity at 48 h post-injury relate to microscopic changes and
      LDH release into the medium during that time, and finally to explore the possible
      mechanisms of hypoxic injury in this model. At exposure to 0.5-1.5% O2 there was
      a time-dependent decrease in ChAT activity when cells were harvested 48 h after
      exposure. Forty-eight hours after 8-9 h hypoxic exposure ChAT activity was 50-60%
      that of controls without any alteration in morphology of neurons. An 8 h exposure
      to hypoxic conditions caused a post-exposure time-dependent decrease in ChAT
      activity to 20% of control level at 72 h. Thereafter there was spontaneous
      recovery of phenotype to 60% of control which remained stable between 5 and 7
      days post-exposure. Loss of neurotransmitter phenotype was not well correlated
      with other measures of cytotoxicity including morphological changes and LDH
      release. The loss of phenotype observed with hypoxia was mimicked by glutamate
      and kainate but not by NMDA. Consistent with these observations, neither APV nor
      AP3 significantly altered the effect of hypoxia on forebrain cholinergic neurons,
      while the addition of APV and CNQX in combination protected the phenotype of
      these neurons only if there was 50% or less loss of phenotype following
      hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354563
TI  - Activation of kappa-opioid receptors depresses electrically evoked excitatory
      postsynaptic potentials on 5-HT-sensitive neurones in the rat dorsal raphe
      nucleus in vitro.
AB  - Intracellular recordings from dorsal raphe neurones in slices from rat brains
      were used to study the actions of kappa-opioid receptor agonists on an excitatory
      postsynaptic potential (epsp) evoked by local electrical stimulation of afferent
      terminals. The epsp was observed on all 5-HT-sensitive neurones and was blocked
      by 1 microM TTX. The epsp was reduced in a dose-dependent manner by the specific
      kappa-opioid receptor agonist [5R-(5 alpha,7 alpha,8 beta)]-N-methyl-N-[7-(1
      pyrrolidinyl)-1- oxaspiro[4.5]dec-8-yl]-4-benzofuranacetamide monohydrochloride
      (CI-977) (1-100 nM). The effects of CI-977 were blocked by the specific kappa
      opioid receptor antagonist norbinaltorphimine (NorBNI) (0.1-1 microM). In the
      presence of the GABAA receptor antagonists picrotoxin and bicuculline (30
      microM), CI-977 still had its depressant action on the epsp. Application of the
      excitatory amino acid receptor antagonists either kynurenic acid (0.5-1 mM) or 6
      cyano-2,3-dihydro-7-nitro-quinoxaline-2,3-dione (CNQX) (30 microM) and DL-2-amino
      5-phosphonovaleric acid (APV) reduced both the peak and area of the epsp
      suggesting that the main component of the epsp evoked by electrical stimulation
      was largely due to release of excitatory amino acids from afferent terminals.
      Using potassium chloride-filled recording electrodes an epsp which was only
      partially occluded by kynurenic acid or CNQX and APV was seen on some neurones,
      this residual epsp was insensitive to CI-977 but was blocked by 30 microM
      picrotoxin and bicuculline. The specific mu-opioid receptor agonist, DAGOL, had
      no consistent effect on the fast epsp. Longer duration electrical stimuli
      produced a slow inhibitory postsynaptic potential (ipsp) and a long duration
      increase in firing. CI-977 did not affect either the slow 5-HT-mediated ipsp
      which was blocked by spiperone or the slow noradrenaline-mediated increase in
      firing which was sensitive to prazosin. CI-977 did not change the depolarizing
      response to brief applications of either glutamic acid or N-methyl-D-aspartic
      acid (NMDA). CI-977, NorBNI, naloxone, DAGOL, picrotoxin, bicuculline and
      kynurenic acid had no consistent effects on the resting postsynaptic membrane
      potential or conductance. Under voltage-clamp conditions CI-977 had no effect on
      a membrane current resembling IA. These results suggest that kappa-opioid
      receptors are present on the terminals of afferents which release excitatory
      amino acids onto the 5-HT-sensitive neurones in the raphe.

PMID- 1354564
TI  - Lateral hypothalamus and local stimulation induced postsynaptic responses in zona
      incerta neurons in an in vitro slice preparation of the rat.
AB  - Postsynaptic potentials evoked in the zona incerta (ZI) neurons were studied in
      in vitro slice preparations. Lateral hypothalamus (LH) and local stimulation
      evoked fast IPSPs, fast EPSPs, and slow EPSPs. The amplitude of the slow EPSPs
      increased when the neuron was hyperpolarized by a low intensity current injection
      but was blocked when it was hyperpolarized with a strong current. The slow EPSPs
      were reversibly suppressed by an application of 50 microM DL-2-amino-5
      phosphonovaleric acid (APV) and 20 microM 3-[(+/-)-2-carboxypiperazine-4-yl-]
      propyl-1-phosphonic acid (CPP). The slow EPSPs were augmented in Mg-free medium
      and by train pulse stimulation. Pressure application of NMDA induced a
      depolarization similar to the slow EPSP. On the other hand, the fast EPSPs showed
      a conventional voltage dependency and were antagonized by kynurenic acid but not
      by APV or CPP. The fast IPSPs were completely blocked by 10 microM bicuculline
      methiodide. The results indicate that LH and local stimulation evoked
      monosynaptic fast EPSPs and slow EPSPs mediated by N-methyl-D-aspartate (NMDA)
      and non-NMDA receptors, respectively. The IPSPs appear to be mediated by GABAA
      receptors and regulate the expression of NMDA receptor-mediated slow EPSPs.

PMID- 1354565
TI  - Dopamine microinjected into the nucleus ambiguus elicits vagal bradycardia in
      spinal rats.
AB  - To investigate the effects of dopamine (DA) on vagal efferent activity, DA was
      microinjected into the right nucleus ambiguus (NA) in rats. Experiments were done
      in 19 urethane anaesthetized, artificially ventilated spinal (C1) rats. Sites in
      the right NA containing cardioinhibitory neurons were identified by observing a
      marked and reproducible decrease in heart rate (HR; 64.9 + 2.8 bpm; n = 36)
      elicited by microinjecting L-glutamate (GLU; 1.5. nmol in 10 nl). No decreases in
      arterial pressure (AP) were obtained at these sites. Microinjection of DA (1-15
      nmol in 10 nl) into 24 of these 36 sites caused a dose-dependent decrease in HR.
      The responses to 1 nmol and 3 nmol DA were blocked by (+/-)-sulpiride, a specific
      D2 receptor antagonist (0.1 nmol in 10 nl). A higher dose of (+/-)-sulpiride (1
      nmol in 10 nl) was required to block the responses to 15 nmol of DA. Bradycardia
      elicited by even the lowest amount of DA (1 nmol) was not blocked by SCH-23390, a
      specific D1 receptor antagonist. These experiments demonstrate that the
      bradycardia caused by microinjection of DA into the NA is due to the excitation
      of dopamine D2 receptors present on vagal preganglionic cardioinhibitory neurons
      controlling HR.

PMID- 1354566
TI  - Comparative inhibition profiles of three non-sedating antihistamines assessed by
      an extended Lewis model.
AB  - Antihistaminic drugs are widely prescribed across a multitude of medical
      specialties such as Allergy and Dermatology. The potentially serious sedative
      effect of these valuable agents has previously restricted their full use and the
      choice of drug has been dictated more by individual patient acceptability than by
      any laboratory demonstrations of comparative efficacy. Unsurprisingly therefore,
      there is a trend towards prescribing those newer preparations which leave the
      central nervous system unclouded. We have studied the most frequently prescribed
      non-sedating antihistamine preparations, terfenadine (Triludan, Triludan Forte),
      cetirizine (Zirtek) and loratadine (Clarityn) in pharmacodynamic and relative
      efficacy trials using a quantifiable and reproducible extension of the classic
      Lewis model. The results indicate that two preparations, terfenadine 120 mg
      (Triludan Forte) and cetirizine 10 mg (Zirtek) are superior to their immediate
      rivals in degree of efficacy and/or speed of action. These results should assist
      clinicians in the positioning of effective, rapidly acting antihistamines for the
      symptomatic treatment of immediate hypersensitivity reactions such as urticaria
      and rhinitis.

PMID- 1354567
TI  - Beta agonists and asthma mortality: deja vu.

PMID- 1354568
TI  - Changes in acute myocardial infarction risk and patterns of practice for patients
      older and younger than 70 years, 1987-90.
AB  - OBJECTIVE: To evaluate temporal changes in risk and patterns of hospital practice
      for acute myocardial infarction (AMI). DESIGN/PATIENTS: Retrospective analysis of
      age-related medical therapy and outcome of 342 consecutive patients (132 at least
      70 years old and 210 younger than 70) with AMI between July 1, 1989, and June 30,
      1990, and comparison with data from two previous analyses of AMI practice in 1987
      (n = 207) and 1988-89 (n = 402). SETTING: Tertiary care medical centre.
      INTERVENTIONS: No direct interventions; results of the two previous AMI practice
      pattern analyses, however, were propagated during the practice time of the most
      recent analysis. RESULTS: In 1989-90, hospital mortality was higher (19%) among
      patients at least 70 years old compared with patients younger than 70 (8%) (P
      less than 0.01). Therapies proven by repeated clinical trials to be effective in
      reducing AMI risk were all used less frequently in patients aged at least 70
      years: thrombolysis (20 versus 43%); beta-blockers (41 versus 62%);
      acetylsalicylic acid (71 versus 87%); and nitrates (86 versus 97%).
      Qualitatively, these age-specific patterns of AMI mortality and therapy were
      similar to previous studies. Quantitatively, however, comparing 1987 with 1989-90
      demonstrated parallel and marked increases in the use of all proven medications
      in both age groups, ranging from 42 to 230% (P less than 0.01). There was also a
      significant overall decrease in mortality from the 1987 patient cohort (20%) to
      the 1989-90 cohort (13%) (P less than 0.05). The decrease in mortality was
      entirely due to decreased mortality within the group 70 years or older; 35% in
      1987 versus 19% in 1989-90 (P less than 0.05). Mortality in the AMI patients
      younger than 70 years old remained unchanged from 1987 to 1989-90. CONCLUSIONS:
      Pattern of practice analyses were associated with, and may have contributed to,
      improved patient care and outcomes in AMI. Increased use of effective AMI medical
      therapy had a greater benefit in elderly higher risk AMI patients than lower risk
      younger patients. Persisting age-specific differences in AMI therapy may respond
      to more direct quality improvement measures, such as critical path management.

PMID- 1354571
TI  - [Laboratory-confirmed cases of hemorrhagic fever with renal syndrome which
      occurred in Breclav 1989-1990].
AB  - The authors describe the first three cases with a serologically confirmed
      hantaviral aetiology in the Czech Republic. It is the causal agent of
      haemorrhagic fever with renal syndrome, western type (strain CG 18-20, identical
      with the Puumala prototype). All patients come from a locality where since 1984
      very actively a natural focus of hantaviral infection was investigated in small
      mammals, and where formerly groups of farmers were found with a high herd
      immunity with hantavirus. The disease was present in a mild to medium severe form
      with some sequelae. In the discussion the authors draw attention to the necessity
      of wider use of aetiological diagnosis in suspect diseases.

PMID- 1354570
TI  - [Use of DNA analysis in medicine].
AB  - Advances in genetic engineering influence to an increasing extent a number of
      medical disciplines. DNA analysis can be used in the diagnosis of hereditary
      diseases, in investigations of malignant processes, in forensic medicine and for
      detection of infectious pathogens. Two main methodical approaches to DNA
      analysis, Southern's method and procedures based on primer directed enzymatic
      amplification of DNA by the PCR method, resolve the complicated detection of
      slight changes in the vast volume of human genetic information. Cystic fibrosis
      may serve as an example of a serious hereditary disease the diagnosis of which
      improved greatly after introduction of DNA analysis. The diagnosis of this
      disease is nowadays possible by direct analysis of mutations and indirectly by
      investigations of the link between the disease and DNA polymorphisms.

PMID- 1354569
TI  - Contemporary medical management of left ventricular dysfunction and congestive
      heart failure.
AB  - OBJECTIVE: The primary purpose of this review was to address the following
      question: based on the best available evidence, what should be the current
      medical management of congestive heart failure (CHF)? DATA SOURCES: The major
      sources for this review were from searches of the English language literature,
      including computer and bibliography reviews, of all randomized, controlled
      clinical trials and overview analyses of positive inotropic agents,
      preload/afterload reduction agents and beta-blocker medications in CHF. STUDY
      SELECTION: The number of studies reviewed was approximately 40. The major
      criterion for selection was that the studies be of CHF patients in randomized
      controlled clinical trials, particularly with a mortality/survival endpoint.
      Additional clinical trials of nonmortality endpoints in CHF patients and
      mortality trials in non-CHF patients were also selected to support possible
      pathophysiological insights for future CHF trials. DATA EXTRACTION: The data,
      particularly for the accompanying tables, were initially extracted by a single
      reviewer using common qualitative guidelines as far as was possible within the
      different temporal, etiological and geographic frameworks of the original
      component studies. Conclusions are drawn from this data synthesis and from
      published overviews. DATA SYNTHESIS: Angiotensin converting enzyme (ACE)
      inhibition therapy is effective in reducing mortality and morbidity in severe
      left ventricular dysfunction and CHF. Other systemic vasodilators may also be
      beneficial. The effects of digitalis on survival and morbidity in CHF are
      presently uncertain, but should be resolved in the near future. Other inotropic
      agents, at least in the long term, are clinically detrimental. Diuretics decrease
      morbidity, but their effect on mortality in CHF remains unknown. Beta-blocker and
      magnesium therapy offer promise in CHF, but await definitive clinical trials
      evaluation. CONCLUSIONS: The current medical therapy of CHF should definitely
      include ACE inhibitors, probably diuretics and possibly other vasodilators.
      Further viable trials of promising new, and older heretofore under-evaluated, CHF
      therapies are needed. Additionally, innovative strategies are needed to deal with
      this disease which has an increasing prevalence. Two strategies, primary
      prevention of CHF and a 'Heart Function Clinic', are discussed.

PMID- 1354572
TI  - [New findings on alpha-hemolytic strains of E. coli in urinary tract infections.
      I. alpha-hemolysin and adhesins].
AB  - Alphahaemolysin (AH) is one of the important factors of virulence of E. coli
      strains in urinary infections. The synthesis and secretion of AH is coded by four
      HLA genes which in the majority of strains are located on the chromosome.
      Alphahaemolytic strains possess fimbrial and non-fimbrial adhesins.

PMID- 1354573
TI  - Octreotide decreased liver metabolic activity in patients with hepatitis B
      surface antigen-positive cirrhosis.
AB  - The influence of octreotide and somatostatin on liver metabolic activity were
      studied in 16 patients with cirrhosis that was positive for hepatitis B surface
      antigen (HBsAg). In patients receiving a 50 micrograms bolus and a 50
      micrograms/hr infusion of octreotide, the hepatic blood flow, hepatic clearance,
      and the maximum velocity/metabolic elimination rate constant (Vmax/km) were
      significantly reduced after octreotide infusion compared with basal values.
      Similarly, the hepatic blood flow, hepatic clearance, and Vmax/km were
      significantly decreased in patients receiving a 250 micrograms bolus and a 250
      micrograms/hr infusion of somatostatin. The extraction ratio and the systemic
      hemodynamic values, including cardiac index, heart rate, mean arterial pressure,
      and systemic vascular resistance, showed no significant changes in patients
      receiving either octreotide or somatostatin. These findings suggest that, as with
      somatostatin, octreotide reduced hepatic blood flow and impaired liver metabolic
      activity in patients with HBsAg-positive cirrhosis. These effects may have
      important clinical implications in the management of bleeding esophageal varices
      in patients with cirrhosis.

PMID- 1354574
TI  - Comparison of insulin-like growth factor interaction with satellite cells and
      embryonic myoblasts derived from the turkey.
AB  - 1. The interaction of insulin-like growth factors (IGFs) with receptors on clonal
      derived turkey satellite cells and embryonic myoblasts was compared using
      competitive binding assays and affinity cross-linking analysis. 2. Although
      [125I]IGF-I and [125I]IGF-II were displaced similarly by IGF-I and IGF-II within
      cell lines (P greater than 0.05), displacement, and therefore dissociation
      constants, differed between cell lines (P less than 0.0001). 3. Receptor cross
      linking analysis using iodinated IGFs suggests that both IGF-I and IGF-II
      interact with the type I receptor on turkey embryonic and posthatch myogenic
      cells.

PMID- 1354575
TI  - Effect of triiodothyronine on cAMP-dependent and cAMP-independent protein kinase
      activities in developing chick embryo liver.
AB  - 1. Changes in liver cytosol cAMP-dependent kinase and cAMP-independent growth
      related quercetin-inhibited casein kinase activities during chick embryo
      development were studied. 2. Both kinase activities were found to increase
      continuously during the experimental period. 3. Upon treatment of embryos with
      triiodothyronine, an activation of cAMP-dependent kinase A and cAMP-independent
      casein kinase was observed which was most pronounced on days 12 and 14.

PMID- 1354576
TI  - Adaptation effect of sucrose on the salt taste response.
AB  - 1. Intracellular recordings from mouse taste receptor cells were made to study
      cellular adaptation properties. 2. The sugar and salt receptor mechanisms of
      mammalian taste cells were investigated with cross-adaptation experiments. 3. The
      responding of taste cells to sucrose as well as to NaCl does not contradict the
      independency of their binding mechanisms. 4. With a mixture of sucrose and NaCl,
      different adsorption mechanisms are observed. 5. From these observations, it was
      concluded that adaptation occurs in the taste receptor cell.

PMID- 1354577
TI  - Oxygen dependency of synaptic transmission at the squid Loligo pealei giant
      synapse.
AB  - 1. Synaptic transmission at the squid giant synapse was blocked in 45 min by
      exposure to 0.02 atm oxygen but was maintained for more than 90 min in air (0.21
      atm oxygen) or pure oxygen (1 atm). 2. Excitatory post-synaptic potential
      amplitude decreased in 0.02 atm oxygen but did not change in either 1 or 0.21 atm
      oxygen. Fast facilitation was increased in 0.02 atm oxygen only. 3. Post-synaptic
      resting membrane potential (Vm) and input resistance (Ro) remained unchanged in 1
      or 0.21 atm oxygen but Ro was increased in 0.02 atm oxygen. 4. Our results
      suggest that severe hypoxia decreased the release of transmitter from the pre
      synaptic terminal.

PMID- 1354578
TI  - D-glucose transport activities in erythrocytes and hepatocytes of dogs, cats and
      cattle.
AB  - 1. The activities of D-glucose transport and hexokinase were investigated in
      erythrocytes or hepatocytes of dogs, cats and cattle. 2. The mean D-glucose
      transport activity in erythrocytes of dogs was 6.0 nmol/min/mg protein, half the
      value of hepatocytes. 3. The activities of D-glucose transport in erythrocytes
      and hepatocytes or hepatic hexokinase of cats were about one-third of those of
      dogs. 4. Cattle with low blood glucose concentrations showed considerably low
      activities of D-glucose transport and hexokinase, about one-third of those of
      dogs.

PMID- 1354579
TI  - Seasonal temperature and its influence on plasma corticosterone,
      triiodothyronine, thyroxine, plasma protein and packed cell volume in mature male
      chickens.
AB  - 1. The relationship between seasonal changes in environmental temperature and
      hematological parameters was investigated in mature, single comb white leghorn
      (SCWL) male chickens. 2. Samples of blood plasma, obtained monthly from two
      groups of birds over two separate 12 month periods, were analysed for
      corticosterone (CT), 3,5,3'-triiodothyronine (T3), thyroxine (T4), plasma protein
      (PP), and packed cell volume (PCV). 3. Statistical analyses revealed that blood
      plasma concentrations of T3 were significantly correlated negatively with monthly
      dry-bulb temperatures. 4. There were no consistent or significant relationships
      between monthly dry-bulb temperature and CT, T4, PP or PCV over the two 12 month
      periods. 5. The results of this study indicate that blood plasma concentrations
      of T3 are influenced by season of year in mature, male domestic fowl.

PMID- 1354580
TI  - Comparative hematology in marine fish.
AB  - 1. A comparative study involving 80 species (14 ray, 14 shark and 52 teleost
      species) of marine fish found at the southeastern Brazilian coast is presented.
      2. Active species displayed higher values for all hematological parameters
      studied when compared to the less active forms. 3. Mean values of hematocrit,
      hemoglobin concentration and red blood cell counts increased according to the
      sequence: rays, sharks, teleosts. 4. As a group, cartilaginous fish blood
      displayed larger and fewer erythrocytes containing more hemoglobin than teleosts;
      mean cell hemoglobin concentration was significantly higher in rays and sharks
      than in teleosts. 5. For all but the hemoglobin concentration, the hematological
      values studied revealed a marked contrast between bony and cartilaginous fishes
      which suggests distinct ways to accomplish their oxygen demands.

PMID- 1354581
TI  - Erythrocytic nucleoside triphosphates in marine fish.
AB  - 1. Whole blood purine nucleotides were determined in 19 species of selachians and
      27 species of marine teleosts. Concomitant ATP and GTP were revealed inside the
      erythrocytes of almost all species studied. 2. ATP seems to be the main potential
      modulator of oxygen affinity in rays, sharks and teleosts, and GTP was not
      detected in only two teleost species. 3. The mean erythrocytic NTP concentration
      and the ratio between NTP and intraerythrocytic Hb concentrations in rays were
      the lowest (2.3 mM and 0.6 respectively), increasing in sharks (3.8 mM and 1.0),
      and further in teleosts (5.9 mM and 2.1). 4. The intraerythrocytic phosphate
      contents probably reflect different adaptative strategies associated with the
      fish habits and habitats, and with the Root effect expression.

PMID- 1354582
TI  - The effects of feeding triiodothyronine on reproductively inhibited prairie
      deermice (Peromyscus maniculatus bairdii) from laboratory populations.
AB  - 1. Two reproductively inhibited populations were given 250 ng triiodothyronine
      (T3) per gram of food for 35 days to elevate the reduced serum thyroid hormone
      concentration previously demonstrated in reproductively inhibited animals and to
      determine if the treatment would promote recovery. 2. Per capita food intake was
      significantly increased but per cent body fat tended to decrease and body weight
      did not significantly increase during T3 treatment. 3. Mean testis and seminal
      vesicle weights of T3-treated males were significantly increased and testis
      histology indicated some increase in spermatogenesis. 4. Mean ovary weights of T3
      treated females only tended to increase although the uterine weights were
      significantly increased and ovarian histology revealed a significant increase in
      preovulatory follicles. 5. The limited recovery of reproductively inhibited
      animals may indicate that thyroid activity per se is related to, but not the
      direct cause of, the reproductive inhibition observed in populations.

PMID- 1354583
TI  - Oxytocin and vasopressin change the activity of the contractile vacuole in
      Tetrahymena: newer contributions to the phylogeny of hormones and hormone
      receptors.
AB  - 1. Primary interaction with oxytocin accounted for a significant prolongation of
      the time interval between two systolic contractions of the contractile vacuole in
      Tetrahymena, whereas primary interaction with vasopressin had no appreciable
      influence on that functional parameter. 2. Primary treatment (imprinting) with
      vasopressin increased sensitivity to vasopressin and reduced responsiveness to
      oxytocin. 3. Primary treatment (imprinting) with oxytocin did not increase
      cellular response either to oxytocin or to vasopressin on second exposure. 4.
      Oxytocin, which is chemically related to the antidiuretic hormone vasopressin,
      influences the water metabolism in protozoa; vasopressin develops a similar
      effect after imprinting. 5. The experimental observations allow conclusions on
      certain events involved in the phylogenesis of hormones and receptors.

PMID- 1354584
TI  - Temporal evaluation of fatty acid-binding protein (FABP) activity in association
      with the development of atherosclerosis in the rabbit.
AB  - 1. The relationship between atherosclerosis development and changes in arterial
      fatty acid binding protein (FABP) activity was investigated in the aortas of New
      Zealand rabbits which were fed an atherogenic diet containing 1% cholesterol and
      3% peanut oil for 16 weeks. 2. At 4-week intervals, FABP activity, cholesterol
      and microsomal acylCoA:cholesterol acyltransferase (ACAT) activity were
      determined in aortic tissue and serum cholesterol was measured; age-matched
      normal rabbits served as control comparators. 3. Serum cholesterol increased from
      35 mg/dl in the normal rabbits to 2290 mg/dl in the 16-week cholesterol-fed
      rabbits. 4. The microsomal fraction isolated from cholesterol-fed rabbit aortas
      exhibited a progressive elevation in ACAT activity as time on the diet increased.
      By 12-16 weeks, ACAT activity had increased approximately 10-fold relative to
      normal activity. 5. Arterial cholesterol content of the cholesterol-fed animals
      increased from less than 2 mg/g wet weight to greater than 10 mg/g wet weight at
      12 and 16 weeks. In contrast, arterial FABP activity gradually decreased with
      time on the cholesterol diet; a significant decrease (P less than 0.05) was
      observed at 16 weeks, where palmitoyl CoA binding was decreased from 61.0 to 36.3
      pmol/mg protein. 6. In the cholesterol-fed rabbits, total arterial cholesterol
      and ACAT activity showed a significant (P less than 0.05) inverse correlation to
      FABP activity with correlation coefficients of -0.93 and -0.95, respectively. 7.
      Additionally, FABP activity increased significantly (P less than 0.05) in the 16
      week normal rabbit as compared to the 4-week normal rabbit, suggesting an age
      dependent interaction.

PMID- 1354585
TI  - Effect of lithocholic acid feeding on plasma lipoproteins and binding of
      radioiodinated human lipoproteins to hepatic membranes in rats.
AB  - 1. Male Sprague-Dawley rats fed diets containing 0.25% lithocholic acid for 6
      weeks exhibited elevated serum cholesterol. 2. The rats were fed diets containing
      5 or 20% fat with and without the lithocholate and/or oxytetracycline-HCl. 3. The
      cholesterol elevation was associated with high density lipoprotein (HDL) and not
      very low density lipoprotein (VLDL) or low density lipoprotein (LDL). 4. Specific
      binding of human [125I]HDL to hepatic membranes was lowered in lithocholate-fed
      rats, but binding of human [125I]LDL to these membranes was not affected.

PMID- 1354586
TI  - The influence of dietary protein on carcass composition and sexual maturity in a
      randombred population of Japanese quail (R1) and a subline of R1 selected for
      increased body weight.
AB  - 1. Selection for body weight in Japanese quail has altered the protein
      requirements for growth and reproductive development in the selected line and
      randombred control population from which it was developed. 2. In both the
      selected and randombred lines, the protein requirement for growth is different
      from that for maximal reproductive development.

PMID- 1354587
TI  - Growth and development of lines of Japanese quail (Coturnix coturnix japonica)
      divergently selected for body weight at 4 weeks of age.
AB  - 1. Divergent selection for body weight resulted in significant increases and
      decreases in body weight and the relative weight of the pectoralis major breast
      muscle in heavy (HW) and light weight (LW) strains of Japanese quail compared
      with a randombred control strain (R1). 2. The relative weights of the abdominal
      fat pad and total carcass lipid were increased in the HW strain, particularly in
      the females. 3. Sexual maturity was similar in HW and R1 hens but was delayed in
      the LW hens. HW hens laid significantly more double-yolked eggs.

PMID- 1354588
TI  - Changes in plasma glucagon, insulin and tissue metabolites associated with
      prolonged fasting in brown trout (Salmo trutta fario) during two different
      seasons of the year.
AB  - 1. Pyrenean brown trout juveniles (Salmo trutta fario) were fasted for 50 days in
      late winter (experiment 1) and summer (experiment 2). Plasma insulin, glucagon
      and glucose and some metabolites in plasma and in tissues were analysed. 2.
      Glucagon increased significantly on the 3rd day of fasting in the winter
      experiment (controls 653.7 +/- 92.4 pg/ml, fasted 912.7 +/- 135.2 pg/ml), and the
      same tendency was observed on the 5th day in the summer experiment (controls
      430.5 +/- 56.2 pg/ml, fasted 555.5 +/- 95.3 pg/ml). During this initial period of
      fasting, plasma glucose was maintained in both experiments (75.5 +/- 4.7-67.6 +/-
      4.1 mg/100 ml), but from day 8, glucose and glucagon decreased simultaneously. 3.
      Insulin decreased from the beginning of fasting, reaching lowest values after 50
      days of fasting (winter experiment: controls 6.4 +/- 0.3 ng/ml, fasted 1.6 +/-
      0.1 ng/ml; summer experiment: controls 4.8 +/- 0.1 ng/ml, fasted 1.2 +/- 0.2
      ng/ml). Glucagon/insulin molar ratio (G/I) increased after 3 days in the winter
      experiment (controls 0.21 +/- 0.02, fasted 0.39 +/- 0.05), while in the summer
      experiment, the ratio rose from day 5 and reached a peak at day 30 (controls 0.16
      +/- 0.02, fasted 0.48 +/- 0.07). 4. Muscle proteins were significantly mobilized
      after 50 days of fasting. Visceral index decreased significantly after day 15
      while liver glycogen was already significantly lower at day 8. However, in the
      summer experiment, a transitory increase of liver glycogen was observed at day
      30, coinciding with the peak of G/I.

PMID- 1354589
TI  - The influence of high dietary protein, energy and mineral intake on deficient
      young camel (Camelus dromedarius)--I. Changes in metabolic profiles and growth
      performance.
AB  - 1. The main forage for camels in northern Djibouti (mangrove with Avicennia
      marina) is very poor in nitrogen and energy. In a trial, 32 young camels (less
      than 2 years old) were used in four groups of eight each. 2. All the camels
      received mangrove as basal diet ad lib. 3. After 1 month, the camels received
      mineral supplementation in copper and zinc (groups 1 and 3) or/and a concentrate
      rich in protein and energy (groups 2 and 3) or continued with the basal diet
      (controls). 4. Any supplementation was stopped after 2 months for 1 month. 5.
      Growth performance was 550 g/day (concentrate-supplemented camels) and 570 g/day
      (concentrate+mineral-supplemented camels). 6. The growth was negative for the two
      others groups (-260 g/day). 7. Food intake of mangrove was slightly more
      important with mineral supplementation only and with mineral+concentrate
      supplementation. 8. The changes in metabolic profiles have shown an important
      catabolism in non-supplemented animals, an increase of urea and free fatty acid
      concentrations in plasma and a decrease of glucose concentrations. 9. Three
      camels died in the control group with symptoms of starvation and signs of liver
      damage (increase of liver enzymes glutamate dehydrogenase and gamma-glutamyl
      transferase).

PMID- 1354590
TI  - The influence of high dietary protein, energy and mineral intake on deficient
      young camel (Camelus dromedarius)--II. Changes in mineral status.
AB  - 1. Mangrove Avicennia marina is poor in some trace elements such as copper, zinc
      and manganese. In a trial we used 32 young camels divided into four groups. 2.
      Groups 1 and 3 were supplemented with copper and zinc in drinking water after 1
      month of mangrove feeding. 3. Groups 2 and 3 received concentrate rich in protein
      and energy. The supplementation was stopped after 2 months. 4. All the camels
      were deficient in trace elements at the beginning of mineral supplementation. 5.
      The plasma concentration of copper increased significantly up to normal levels
      (less than 70 micrograms/100 ml) in energy protein supplemented groups, but the
      quantity supplied (100 mg of copper sulphate/day) was not sufficient to maintain
      this level after the end of supplementation. 6. The original zinc deficiency was
      too severe to observe a significant effect of the mineral supplementation. 7.
      Calcium, magnesium and phosphorus levels were improved during the supplementation
      period in protein-energy supplemented groups. 8. A high interaction between
      mineral absorption and quality of the diet was observed. A well-balanced diet
      seems essential to avoid deficient mineral status.

PMID- 1354591
TI  - Report of the Second International Workshop on Human Chromosome 16 Mapping.

PMID- 1354592
TI  - 2nd International Workshop on Human Chromosome 16 Mapping. Adelaide, South
      Australia, February 26-28, 1992. Abstracts.

PMID- 1354593
TI  - Third International Workshop on Human Chromosome 17 Mapping.
AB  - Highlights of the meeting this year include progress in merging two independently
      derived genetic maps, expansion of the composite hybrid breakpoint map, and
      enhancements in working group communications through the chromosome 17 file
      server at Baylor. Progress is also being made in developing STS primers for
      framework markers and reference markers. The task remains of fully reconciling
      the framework map and composite breakpoint map with the list of chromosome 17
      reference markers (Solomon and Ledbetter, 1991). There remain several gaps in the
      overall map, particularly near the distal end of the long arm, where there has
      been limited activity.

PMID- 1354594
TI  - Detection of retinoblastoma gene copy number in metaphase chromosomes and
      interphase nuclei by fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) was applied to detect the copy number
      of the retinoblastoma (RB1) tumor suppressor gene in metaphase chromosomes and
      interphase nuclei. We used 14 lambda phage clones spanning the whole RB1 gene
      region as a probe and obtained a specific hybridization signal in normal
      metaphase chromosomes at 13q14. Normal interphase nuclei showed two RB1 signals
      in about 90% of cases, whereas two cell lines with cytogenetically defined
      deletions involving the RB1 gene showed only one hybridization signal in about
      80% of the nuclei. Analogous changes were detected in metaphase chromosomes.
      Multicolor FISH with subsets of the phage clones allowed visualization of
      subregions within the 200-kb gene in interphase nuclei. Analysis of clinical
      breast cancer samples showed that most of the cells contained two copies of the
      RB1 gene, even when restriction fragment length polymorphism analysis showed loss
      of heterozygosity (LOH) at the RB1 locus. This indicates that LOH at the RB1
      locus in breast cancer cells probably involves mechanisms other than physical
      deletion.

PMID- 1354595
TI  - Localization of two new DNA markers on the linkage map of human chromosome 6q.
AB  - Recently, an autosomal homolog of the dystrophin gene (DMDL) was identified on
      chromosome 6q24. As part of our analysis of the DMDL locus, we endeavoured to
      isolate DNA markers to further define the genetic map of this region. We have
      isolated and characterized two new genetic markers in the region of the DMDL
      locus, the RFLP D6S129 and a (CA)n dinucleotide repeat polymorphism within the
      DMDL gene itself and have positioned them on the existing genetic map of
      chromosome 6q. These markers will be important in testing the hypothesis that the
      DMDL gene is the locus responsible for autosomal forms of neuromuscular disease.

PMID- 1354596
TI  - Linkage of the thyroid peroxidase locus (Tpo) to markers in the proximal part of
      chromosome 12 of the mouse.

PMID- 1354598
TI  - 30th Annual American Cytogenetics Conference. Virginia Beach, Virginia, March 15
      18, 1992. Abstracts.

PMID- 1354597
TI  - Localization of mouse parathyroid hormone-like peptide gene (Pthlh) to distal
      chromosome 6 using interspecific backcross mice and in situ hybridization.
AB  - The single copy parathyroid hormone-like peptide gene (Pthlh) was mapped to
      distal mouse chromosome 6 using genetic linkage analysis with a panel of DNA
      samples from interspecific backcross mice. In all 114 meiotic events examined,
      the Pthlh locus cosegregated with the locus for the Kirsten ras-2 gene (Kras-2)
      which was previously localized to distal mouse chromosome 6. In addition, Pthlh
      was localized to chromosome 6 band F-G and the mouse parathyroid hormone Pth was
      localized to chromosome 7 band F, by in situ hybridization. These studies confirm
      the previous localization of Pthlh to mouse chromosome 6 using somatic cell
      hybrids and show that the Pthlh/PTHLH locus is a part of a conserved linkage
      group between distal mouse chromosome 6 and the proximal segment of the short arm
      of human chromosome 12.

PMID- 1354599
TI  - [Early summer meningoencephalitis vaccination].

PMID- 1354600
TI  - Inguinal hernia in paediatric age-group: Ibadan experience.
AB  - Ninety-nine children with inguinal hernia undergoing elective surgery over a 2
      year period at the University College Hospital, Ibadan, were studied. These were
      all indirect inguinal hernias. There was a male-female ratio of 5.6:1. Fifty-six
      per cent of cases were located on the right side, twenty-eight per cent of cases
      on the left side, and fifteen per cent were bilateral. Ipsilateral hydrocoeles
      and ipsilateral undescended testes were in 8% and 19% of cases respectively.
      There was no significant morbidity, mortality or recurrence in this series.

PMID- 1354601
TI  - Evidence for protein kinase-C mediation of the neurotensin-induced activation of
      tyrosine hydroxylase in tuberoinfundibular dopaminergic neurons.
AB  - The purpose of the present study was to determine whether neurotensin acts within
      the arcuate nucleus/median eminence to activate tyrosine hydroxylase (TH) within
      tuberoinfundibular dopamine neurons. The role of Ca2+/phospholipid-dependent
      protein kinase (protein kinase-C) in the regulation of TH and its involvement in
      the neurotensin-induced activation of TH within tuberoinfundibular dopamine
      (TIDA) neurons also was investigated. The activity of TH within TIDA neurons was
      assessed by quantification of the formation of 3,4-dihydroxyphenylalanine in the
      arcuate nucleus/median eminence after inhibition of 3,4-dihydroxyphenylalanine
      decarboxylase. Neurotensin (0.1-10 nM) increased the activity of TH within the
      arcuate nucleus/median eminence under in vitro conditions by approximately 80%.
      The activity of TH in the arcuate nucleus/median eminence also was increased
      approximately 55% by the phorbol ester 12-O-tetradecanoyl(phorbol-13-acetate) (1
      100 nM), which activates protein kinase-C. Sphingosine (10 microM), an inhibitor
      of protein kinase-C, attenuated the activation of TH within TIDA neurons that was
      induced by both 12-O-tetradecanoyl(phorbol-13-acetate) and neurotensin.
      Sphingosine alone did not alter the activity of TH, nor did it alter the
      (Bu)2cAMP-induced activation of TH in the arcuate nucleus/median eminence. It is
      concluded that neurotensin acts directly within the arcuate nucleus/median
      eminence to activate TIDA neurons. Furthermore, it is suggested that the activity
      of TH within these neurons is enhanced after the activation of protein kinase-C
      and that protein kinase-C may mediate the neurotensin-induced activation of TH
      within these hypothalamic dopamine neurons.

PMID- 1354602
TI  - Beta 1-adrenergic regulation of the GT1 gonadotropin-releasing hormone (GnRH)
      neuronal cell lines: stimulation of GnRH release via receptors positively coupled
      to adenylate cyclase.
AB  - The release of GnRH evoked by norepinephrine (NE) was studied in GT1 GnRH
      neuronal cell lines in superfusion and static cultures. GnRH release from static
      cultured GT1-7 cells was stimulated by NE in a dose-dependent fashion. This
      effect was mimicked by the nonsubtype-selective beta-adrenergic agonist
      isoproterenol and blocked by the beta-adrenergic antagonist propranolol and the
      beta 1-adrenergic subtype-specific antagonist CGP 20712A. However, the
      stimulation of GnRH release by NE was not affected by the beta 2-, alpha-, alpha
      1-, or alpha 2-adrenergic antagonists ICI 118.551, phentolamine, prazosin, or
      yohimbine, respectively. Superfusion of GT1-1 cells with NE for 60-100 min
      resulted in rapid and sustained increases in GnRH secretion. The NE-stimulated
      GnRH release showed a higher amplitude and longer duration than the spontaneous
      GnRH pulses characteristic of GT1-1 cells. In parallel to the stimulation of GnRH
      release, NE also rapidly increased (first observed at 60 sec) the intracellular
      concentration of cAMP in isobutylmethylxanthine-pretreated GT1-1 and GT1-7 cells
      in a dose-dependent fashion. The stimulation of intracellular cAMP concentration
      was also mimicked by isoproterenol and blocked by propranolol and CGP 20712A. In
      addition, GT1 cells express beta 1- but not beta 2-adrenergic receptor mRNA, as
      probed by Northern blot analysis. These results demonstrate a direct stimulatory
      effect of NE on GnRH neurons. The pharmacological evidence and the mRNA analysis
      are consistent with NE acting through a beta 1-adrenergic receptor positively
      coupled to adenylate cyclase.

PMID- 1354603
TI  - Transcriptional antagonism of phorbol ester-mediated induction of plasminogen
      activator inhibitor types 1 and 2 by cyclic adenosine 3',5'-monophosphate.
AB  - Gene expression of plasminogen activator inhibitor (PAI) types 1 and 2 is
      modulated by the protein kinase-C (PKC) and cAMP-dependent protein kinase-A (PKA)
      signal transduction pathways. To determine whether the PKC and PKA pathways
      functionally interact during modulation of PAI gene expression, we assessed
      changes in gene transcription rates, mRNA, and antigen levels of PAI-1 and PAI-2
      in HT-1080 fibrosarcoma cells treated with the PKC activator phorbol 12-myristate
      13-acetate (PMA), alone or in combination with cAMP agonists and analogs. PMA
      produced a transient increase in PAI-1 and a sustained increase in PAI-2, which
      was evident at the level of gene transcription and mRNA. Treatment with the cAMP
      agonist forskolin or the cAMP analog 8-bromo-cAMP decreased constitutive and PMA
      mediated expression of PAI-1 mRNA. PAI-2 mRNA was below detection limits in
      nontreated and cAMP-treated cells. However, elevated levels of cAMP reduced the
      stimulatory effect of PMA on PAI-2 mRNA. The antagonism of the PMA effect by cAMP
      was evident at the level of gene transcription, suggesting that the end point of
      the functional interplay between the PKC and PKA pathways requires modulation of
      a nuclear transcription factor(s). Our results suggest that the PKC- and PKA
      dependent signaling pathways have counteractive effects on transcriptional
      expression of the PAI-1 and PAI-2 genes in HT-1080 cells.

PMID- 1354605
TI  - Beta-endorphin innervation of dopamine neurons in the rat hypothalamus: a light
      and electron microscopic double immunostaining study.
AB  - Pharmacological data suggest that opiates, acting indirectly via the
      catecholaminergic system, are involved in the inhibition of LH release and the
      stimulation of PRL secretion. The aim of this study was to demonstrate on the
      ultrastructural level whether beta-endorphin-immunoreactive fibers form synaptic
      contacts with hypothalamic dopaminergic neurons. Light and electron microscopic
      double immunostaining experiments were performed on vibratome sections prepared
      from the hypothalamus of acrolein-fixed female rat brains. Immunoreactivity for
      beta-endorphin was visualized by a dark blue to black nickel ammonium sulfate
      intensified diaminobenzidine reaction, and in a consecutive immunostaining
      procedure, the tyrosine hydroxylase-immunoreactive dopamine cells were labeled
      with the brown diaminobenzidine reaction product. Under the light microscope,
      beta-endorphin axon terminals were found to contact dopamine cell bodies and
      dendrites throughout the hypothalamus. The majority of opiate target dopamine
      neurons were found in the periventricular area, retrochiasmatic area, and lateral
      part of the zona incerta. A much smaller number was observed in the dorsomedial
      hypothalamic nucleus and the anterior hypothalamus, and only a very few dopamine
      cells could be detected in contact with beta-endorphin axons in the arcuate
      nucleus (particularly in the posterior part where the beta-endorphin cells are
      located) and the medial part of the zona incerta. After light microscopic
      examination and color photography, the double immunostained sections were
      embedded for correlated electron microscopy to verify and characterize the
      putative synaptic connections. Electron microscopy revealed symmetric synaptic
      connections between beta-endorphin-immunoreactive boutons and tyrosine
      hydroxylase-immunopositive cell bodies and dendrites. These results together with
      the observation of dopamine innervation of LHRH-producing neurons and
      progesterone receptor-containing cells indicate that neurons of the hypothalamic
      dopaminergic system probably mediate opiate effects on hypophyseal hormone
      secretion.

PMID- 1354604
TI  - Influence of gastric acid on circulating somatostatin-14 and -28 released after
      insulin-induced hypoglycemia in conscious dogs.
AB  - Insulin hypoglycemia is a potent mechanism for somatostatin secretion into the
      circulation. Whether the associated increase in gastric acid mediates the rise of
      one or both principle molecular forms of somatostatin, somatostatin-14 (S-14) and
      somatostatin-28 (S-28), was examined in four conscious dogs. Somatostatin
      molecular forms were separated by gel filtration chromatography after extraction
      of acidified plasma on octadecyl silyl cartridges and quantified by RIA. Basal
      plasma levels of S-14 and S-28 were 3.4 +/- 0.2 and 4.1 +/- 0.6 fmol/ml,
      respectively. After hypoglycemia induced by insulin, plasma S-14 increased by
      29.5 +/- 3.9 fmol/ml (P less than 0.001), and plasma S-28 increased by 7.2 +/-
      0.9 fmol/ml (P less than 0.01). Suppression of hypoglycemia-mediated gastric acid
      secretion after the administration of omeprazole or ranitidine inhibited
      elevations of S-14 by 82 +/- 6% (P less than 0.001) and 81 +/- 7% (P less than
      0.001), respectively, but had no effect on the rise of S-28. Atropine (50
      micrograms/kg, iv), which also suppresses gastric acid secretion after insulin
      hypoglycemia, decreased S-14 by 59 +/- 3% (P less than 0.01) without influencing
      S-28. Atropine given after omeprazole treatment, however, increased S-14 levels
      observed after atropine (P less than 0.001) or omeprazole (P less than 0.001)
      alone and was equivalent to control levels. S-28 remained unaltered after
      atropine and omeprazole treatment. These results in conscious dogs indicate that
      after vagal stimulation induced by insulin hypoglycemia 1) both S-14 and S-28 are
      released into the circulation, but S-14 predominates; 2) gastric acid contributes
      directly to the stimulation of S-14, but not S-28, secretion; 3) muscarinic
      inhibitory mechanisms participate in the regulation of S-14 secretion, and this
      mechanism is amplified when vagally stimulated gastric acid secretion is
      suppressed; and 4) nonmuscarinic mechanisms mediate in part S-28 secretion. This
      study suggests the presence of a reciprocal functional relationship between
      gastric acid secretion and circulating S-14 that is mediated by vagal muscarinic
      mechanisms.

PMID- 1354607
TI  - Report from the DDW 1992, San Francisco, May 10-13.

PMID- 1354606
TI  - Cross-talk between excitatory and inhibitory amino acids in the regulation of
      luteinizing hormone-releasing hormone secretion.
AB  - Inhibitory (IAA) and excitatory amino acid (EAA) neurotransmitters appear to play
      an important role in regulating reproductive functions. L-Glutamic acid (GLU),
      the major representative of the EAA system, stimulates LHRH release from arcuate
      nucleus-median eminence (AN-ME) fragments in vitro. Several studies have provided
      evidence for considering gamma-aminobutyric acid (GABA), a major IAA
      neurotransmitter, as another regulator of LHRH secretion. Recent reports have
      indicated that a cross-talk between GABA and GLU participates in the regulation
      of synaptic transmission in the brain. In concert with this notion, we present
      evidence indicating that this cross-talk between GABA and GLU appears to be also
      involved in neuroendocrinological paradigms. In this respect, bicuculline, a GABA
      A receptor antagonist, blocked GLU-evoked LHRH secretion from AN-ME fragments in
      vitro without affecting basal LHRH release. In addition, activation of GABA-A
      receptors by muscimol (MUS) stimulated basal LHRH secretion. Interestingly, when
      MUS and GLU were added together to the incubation medium, an additive,
      stimulatory effect was observed. These observations clearly indicate that a
      GABAergic mechanism participates, via GABA-A receptors, in GLU-induced LHRH
      secretion from terminals of the ME. Furthermore, GABA-B receptors appear to
      negatively modulate the effects of GLU. Activation of GABA-B receptors by
      baclofen (BAC) blocked GLU-induced LHRH secretion, while phaclofen, a GABA-B
      receptor antagonist, reversed this effect. In summary, our data provide evidence
      for a cross-talk between EAA and IAA systems in the regulation of LHRH release,
      and, therefore, in the control of gonadal function.

PMID- 1354608
TI  - Errors in sizing bands of hypervariable DNA profiles on autoradiograms: are they
      Gaussian?
AB  - The accuracy of procedures for sizing hypervariable restriction fragments by
      Southern blot analysis (SBA) has been tested under three different experimental
      conditions: (i) intrablot serial analyses: three heterozygous DNA profiles were
      tested 14 times each in the same gel electrophoresis; (ii) intralaboratory
      analyses: we replicated three profiles (six autoradiographic bands) in over 100
      SBA experiments; (iii) interlaboratory analyses: 15 serial measurements produced
      in a recent collaborative study (Forensic Sci. Int. 1991, 49, 1-15) were taken
      into account. In these three cases, a typical U-shaped correlation curve between
      molecular size and coefficient of variation was found. We explain decrease of
      accuracy at both extremities of the gels in terms of: (i) enlarged shapes of
      bands and mean electrophoretic resolution at the cathode; (ii) diffusion and
      blurring of bands at the anodal edge. The three populations of data were
      subjected to a chi 2 test and to the Kolmogorov-Smirnov test in order to verify
      their compliance with normal distribution. Twenty-three out of 27 tests indicated
      no significant deviation from the assumption of Gaussian distribution. We
      recommend the adoption of tests for normality to validate the use of symmetric
      confidence intervals for calculating gene frequencies and asserting a match
      between adjacent bands.

PMID- 1354609
TI  - Deletion studies to reveal the basis for size discrepancy in proliferating cell
      nuclear antigen.
AB  - Proliferating cell nuclear antigen (PCNA), an essential component for DNA
      replication in eukaryotes, is a highly conserved nonhistone nuclear protein of
      261 amino acids. The molecular weight of mammalian PCNA, estimated by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), differs notably
      from that predicted by the cDNA sequences, that is, 36,000 in comparison with
      29,261 and 28,748 for human and rat PCNA, respectively. To investigate if this
      discrepancy is due to posttranslational modifications, we studied the PCNA
      protein synthesized by an in vitro transcription/translation system as well as
      the protein overproduced in bacteria. We found that both PCNA protein samples
      were indistinguishable from the authentic protein from the protein mobility in
      SDS-PAGE. The finding indicates that the size discrepancy is not due to the
      posttranslational modifications. Hence, the size discrepancy may be due to the
      protein sequence per se, namely a sequence-related anomaly in SDS-PAGE. Results
      from the analyses of a series of PCNA derivatives with various lengths of C- or N
      terminal deletion indicate that the putative sequence is in the region of
      residues 128-150.

PMID- 1354610
TI  - v-erbB oncogene expression accounts for most variations in protein synthesis
      after avian erythroblastosis virus infection of chicken embryo fibroblasts: a two
      dimensional electrophoresis study.
AB  - The effect of the v-erbA and/or v-erbB oncogenes on cellular gene expression was
      investigated after separation by two-dimensional polyacrylamide gel
      electrophoresis of [35S]methionine-labelled proteins from chicken embryo
      fibroblasts (CEF), infected by either the avian erythroblastosis virus (AEV)
      carrying both oncogenes, or by viruses carrying only one of them. We observed
      significant changes in the synthesis of 34 proteins in AEV-transformed CEF as
      compared with control cells. The synthesis of 24 of them was increased while the
      synthesis of the other 10 proteins was decreased. The expression of v-erbB alone
      is necessary and sufficient to induce changes in the synthesis of 27 proteins
      while the 7 remaining modifications are observed only in cells expressing v-erbB
      together with v-erbA. Moreover, the deregulation of protein synthesis by v-erbB
      expressing viruses was correlated with the morphological transformation state of
      cells.

PMID- 1354611
TI  - Common accessory genes for the Bordetella pertussis filamentous hemagglutinin and
      fimbriae share sequence similarities with the papC and papD gene families.
AB  - The Bordetella pertussis filamentous hemagglutinin (FHA) is a major virulence
      factor responsible for attachment, one of the early events in bacterial
      pathogenesis. Deletion of its structural gene, fhaB, or a Tn5 insertion in fhaA,
      downstream of fhaB, resulted in a FHA- and fimbriae- phenotype, although fhaB and
      the fim genes are not linked. The fhaB downstream region therefore most likely
      encodes accessory proteins required for the biosynthesis of FHA and fimbriae,
      despite the lack of sequence similarities between these two proteins. The
      nucleotide sequence of this area contains the open reading frames fhaD and fhaA,
      whose products share sequence similarities with the papD and papC gene products,
      respectively. PapD is a periplasmic chaperone protein able to bind to the
      Escherichia coli P pilin subunits and to transport them towards the outer
      membrane protein PapC which is responsible for pilus membrane translocation. An
      additional open reading frame, fhaE, is located downstream of fhaA. Its amino
      acid sequence shares similarities with those of the fimbrial subunits. Deletion
      analyses suggest that fhaB and the downstream genes can be transcribed as a
      polycistronic operon, and primer extension analysis revealed the presence of a
      second promoter between fhaB and fhaD.

PMID- 1354612
TI  - Phosphorylation of CREB affects its binding to high and low affinity sites:
      implications for cAMP induced gene transcription.
AB  - Cyclic AMP treatment of hepatoma cells leads to increased protein binding at the
      cyclic AMP response element (CRE) of the tyrosine aminotransferase (TAT) gene in
      vivo, as revealed by genomic footprinting, whereas no increase is observed at the
      CRE of the phosphoenolpyruvate carboxykinase (PEPCK) gene. Several criteria
      establish that the 43 kDa CREB protein is interacting with both of these sites.
      Two classes of CRE with different affinity for CREB are described. One class,
      including the TATCRE, is characterized by asymmetric and weak binding sites
      (CGTCA), whereas the second class containing symmetrical TGACGTCA sites shows a
      much higher binding affinity for CREB. Both classes show an increase in binding
      after phosphorylation of CREB by protein kinase A (PKA). An in vivo
      phosphorylation-dependent change in binding of CREB increases the occupancy of
      weak binding sites used for transactivation, such as the TATCRE, while high
      affinity sites may have constitutive binding of transcriptionally active and
      inactive CREB dimers, as demonstrated by in vivo footprinting at the PEPCK CRE.
      Thus, lower basal level and higher relative stimulation of transcription by
      cyclic AMP through low affinity CREs should result, allowing finely tuned control
      of gene activation.

PMID- 1354615
TI  - Plasma endogenous opioid levels in acute myocardial infarction patients, with and
      without pain.
AB  - Plasma levels of beta-endorphin, met-enkephalin and dynorphin were assessed in
      acute myocardial infarction (AMI) patients, with and without pain (group I: no
      pain, N = 12; group II: severe pain, N = 16). Plasma opioid peptide concentration
      was measured on admission to hospital (between 1 and 3 h after the myocardial
      infarction onset), at 7, 12, 24 h and at 2, 3 and 4 days. A transient increase in
      plasma beta-endorphin levels was found in AMI patients with severe pain, the
      levels normalizing within 12-18 h when pain had ceased. No changes in beta
      endorphin concentration were observed in AMI patients without pain. Compared with
      healthy subjects, low levels of met-enkephalin were found in both groups of AMI
      patients throughout the study. Low levels of dynorphin were observed in patients
      with no pain while in the other patients initial low levels of dynorphin
      normalized when pain ceased. Blood pressure, heart rate and central venous
      pressure values were normal and did not correlate with plasma opioid levels. The
      results suggest that endogenous opioids do not affect pain in the early phase of
      myocardial infarction. The rise in beta-endorphin concentration observed in
      patients with severe pain seems to be induced by pain stress.

PMID- 1354614
TI  - Zmhox1a, the product of a novel maize homeobox gene, interacts with the Shrunken
      26 bp feedback control element.
AB  - A new maize homeobox gene was isolated by screening a lambda gt11 expression
      library with the 26 bp Shrunken feedback control element. Zmhox1a (Zea mays
      homeobox) is an unidentified maize gene mapping to the long arm of chromosome 8.
      It is a member of a new class of maize homeobox genes only distantly related to
      the Knotted class. The 3.1 kb Zmhox1a transcript can be detected in different
      maize tissues and encodes a polypeptide of 719 amino acids. Western blotting
      experiments detect the native 112 or 115 kDa protein in nuclear protein extracts,
      the nuclear localization being compatible with a function in transcriptional
      control. No Zmhox1a protein is detected in maize roots despite the presence of
      the Zmhox1a transcript; this may indicate a post-transcriptional control
      mechanism. A highly acidic central region of the Zmhox1a polypeptide implies a
      transcriptional activator function. The carboxy-terminal part of the maize
      homeodomain protein is related to the human Oct2 transcription factor, but
      homology to the POU specific domain is restricted to the POU-B subdomain. It was
      confirmed by DNase I footprinting experiments that DNA binding of the Zmhox1a
      homeodomain was at three sites flanking the TATA-box of the Shrunken promoter.

PMID- 1354613
TI  - Transcriptional repression of band 3 and CAII in v-erbA transformed erythroblasts
      accounts for an important part of the leukaemic phenotype.
AB  - The v-erbA oncogene confers two prominent properties on transformed
      erythroblasts: a block of spontaneous differentiation and tolerance to wide
      variations in the pH or ionic strength of culture medium. V-erbA acts as a
      constitutive repressor of erythrocyte-specific gene transcription, arresting the
      expression of at least three different erythroid genes: the erythrocyte anion
      transporter (band 3), carbonic anhydrase II (CAII) and delta-aminolevulinate
      synthase (ALA-S). To test whether or not the v-erbA induced repression of these
      genes is causally related to the v-erbA induced leukaemic phenotype, we have
      reintroduced the genes for band 3 or CAII into transformed erythroblasts via
      retrovirus vectors. We show here that such erythroblasts, expressing v-erbA,
      require the same narrow range of medium pH and ion concentration for growth as do
      transformed erythroblasts lacking v-erbA, i.e. the v-erbA induced tolerance to pH
      variation was abrogated. The v-erbA induced differentiation block, however,
      remained unaffected by the re-expression of band 3 and was only slightly affected
      by the re-expression of CAII. Our experiments show that the two v-erbA-related
      'erythroblast transformation parameters' are separable: suppression of band 3 and
      CAII accounts for one parameter (pH/ion tolerance), while the second parameter
      (differentiation block) must involve v-erbA regulation of a different set of
      target genes.

PMID- 1354616
TI  - Comparative effects of epanolol and diltiazem on exercise performance and
      respiratory gas exchange in angina pectoris.
AB  - The effects of epanolol (a new selective beta-adrenoceptor antagonist), diltiazem
      and placebo were compared in a group of 16 patients with chronic stable angina
      pectoris. Each patient received each treatment in random order. Diltiazem reduced
      weekly angina attack rate from 7.2 (95% CI 3.9-10.5) to 3.9 (1.9-5.9) (P less
      than 0.01), whereas a lesser reduction was observed after epanolol. Both drugs
      produced a small but significant (P less than 0.05) increase in treadmill
      exercise time (placebo 474 s (374-574), epanolol 527 s (431-623) and diltiazem
      554 s (462-646). However, aerobic work capacity, assessed by peak achieved oxygen
      consumption, was not different from the placebo value of 21.2 (18.0-24.4) ml.min
      1.kg-1, and clearly subnormal when compared to age- and sex-matched controls
      (33.0 (30.1-35.9) ml.min-1.kg-1). Ventilatory abnormalities and increased lactate
      levels on active treatment were observed at peak exercise only. We conclude that
      the cardiodepressant effects of both active drugs limit blood supply to working
      skeletal muscle, and that chest pain may be replaced by dyspnoea or fatigue as
      the limiting factors to exercise.

PMID- 1354617
TI  - Effects of mental and physical stress on plasma catecholamine levels before and
      after beta-adrenoceptor blocker treatment.
AB  - In a study in mild hypertensives, the impact of mental and physical stress on
      plasma epinephrine (E), norepinephrine (NE), and on their ratio (NE/E) was
      evaluated. The effect of two beta-adrenoceptor blocking drugs, atenolol and
      bopindolol, on plasma catecholamine levels was also examined. Each stressful
      stimulus significantly increased the NE and E levels compared to rest. The
      increase was progressive from mental stress, through the handgrip test to the
      treadmill test. A slight decrease in the NE/E ratio was observed following mental
      stress and the handgrip test, while this ratio increased during the treadmill
      test. No significant impact of beta blocking treatment on catecholamine levels
      was observed under any test condition.

PMID- 1354619
TI  - Peripheral hematopoietic stem cell transplantation: current concepts.
AB  - As methods for increasing stem cells are perfected and alternate regimens for
      transplantation developed, PSCT will undoubtedly see wider application in
      combination with BMT and may ultimately replace BMT. The initial encouraging
      results with PSCT so far portend a major therapeutic role of this modality in the
      approach to hematologic and oncologic diseases. Prospective randomized trials
      comparing PSCT and BMT in a variety of clinical settings are needed and are
      already underway.

PMID- 1354618
TI  - Acute effect of an alpha 1-adrenoceptor antagonist on urinary sodium excretion,
      plasma atrial natriuretic peptide, arginine vasopressin, and the renin
      aldosterone system in healthy subjects.
AB  - To elucidate the mechanism underlying the sodium retention caused by alpha 1
      adrenoceptor blockade in man, a placebo-controlled, randomised, double-blind
      study has been made of the acute effects of bunazosin an alpha 1-antagonist, on
      urinary sodium excretion, atrial natriuretic peptide (ANP), arginine vasopressin
      (AVP), and the renin-aldosterone system in 7 healthy men. A single oral dose of
      bunazosin 2.0 mg caused a significant reduction (P less than 0.05) in urinary
      sodium excretion after 0-2 h, 2-4 h, and 4-6 h. The mean values for plasma ANP,
      AVP, aldosterone, and cortisol concentrations at those times were similar after
      placebo and bunazosin, and plasma renin activity was significantly increased 2
      and 4 h after bunazosin. Pretreatment with oral enalapril 10 mg, an angiotensin
      converting enzyme inhibitor, did not prevent the bunazosin-induced reduction in
      urinary sodium excretion. There was a significant positive correlation between
      the drug-induced changes in blood pressure and urinary sodium excretion. The
      results suggest that ANP, AVP, and renin-aldosterone may play little role in the
      sodium retention caused by acute alpha 1-adrenoceptor blockade in man.

PMID- 1354621
TI  - European Atherosclerosis Congress (56th EAS meeting). Cagliari, Italy, October 10
      13, 1992.

PMID- 1354620
TI  - Effects of escalating doses of recombinant human interleukin-2 in correcting
      functional T-cell defects following autologous bone marrow transplantation for
      lymphomas and solid tumors.
AB  - High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT)
      in the treatment of malignancies is often associated with immune deficiency
      following transplantation, possibly contributing to tumor relapse or fatal
      infection. Interleukin 2 (IL-2), which enhances major histocompatibility complex
      (MHC)-unrestricted cytotoxicity in vitro, can be applied in vivo as immunotherapy
      to reduce these potential complications. Recombinant human IL-2 (rIL-2) was
      administered by continuous i.v. infusion for four courses in 19 patients
      following ABMT for lymphomas and solid tumors. The patients were assigned to five
      groups of escalating doses of rIL-2 ranging from 3 to 30 x 10(6) IU/m2/day. The
      immunological effects and toxicity were monitored. After a transient reduction of
      lymphocytes in the peripheral blood, a significant lymphocytosis was observed
      during the rIL-2 infusion with an augmentation of CD2+, CD25+, and CD8(+)-Ia+ T
      cells and a dose-related increase of CD56+ lymphocytes. Natural killer (NK)
      activity appeared enhanced in patients treated with as little as 6 x 10(6)
      IU/m2/day. No statistically significant increase in lymphokine-activated killer
      (LAK) activity was seen after rIL-2, when compared to LAK activity following ABMT
      prior to rIL-2 administration. Administration of exogenous rIL-2 to patients who
      have undergone ablative chemotherapy and ABMT has a role in restoring defective T
      cell function. Further trials defining those patients most likely to benefit from
      rIL-2 integrated with ablative chemotherapy and ABMT are now warranted.

PMID- 1354623
TI  - Application of cladistics to the analysis of genotype-phenotype relationships.
AB  - We seek to understand the relative contribution of allelic variations of a
      particular gene to the determination of an individual's risk of atherosclerosis
      or hypertension. Work in progress is focusing on the identification and
      characterization of mutations in candidate genes that are known to be involved in
      determining the phenotypic expression of intermediate biochemical and
      physiological traits that are in the pathway of causation between genetic
      variation and variation in risk of disease. The statistical strategy described in
      this paper is designed to aid geneticists and molecular biologists in their
      search to find the DNA sequences responsible for the genetic component of
      variation in these traits. With this information we will have a more complete
      understanding of the nature of the organization of the genetic variation
      responsible for quantitative variation in risk of disease. It will then be
      possible to fully evaluate the utility of measured genetic information in
      predicting the risk of common diseases having a complex multifactorial etiology,
      such as atherosclerosis and hypertension.

PMID- 1354625
TI  - European general practice research workshop. October 10-13, 1991. Abstracts.

PMID- 1354622
TI  - RFLPs of the LDL-receptor gene: their use in the diagnosis of FH and in
      evaluation of different levels of gene expression on normal subjects.
AB  - The usefulness of the RFLPs of the LDL-receptor gene in early diagnosis of
      Familial Hypercholesterolemia (FH) was investigated in 122 FH-families. Four
      RFLPs, produced by digestion with the enzymes PvuII, ApaLI and AvaII/XbaI were
      able to detect the affected gene and to follow the inheritance of the disease in
      72 out of 97 families (74%). In the remaining 25 families, unambiguous diagnosis
      was possible in 66% of the cases by use of PvuII, ApaLI and BstEII/EcoRI RFLPs.
      The RFLPs were also useful to distinguish true homozygotes from compound
      heterozygotes and to detect families where recombination events occurred or where
      hypercholesterolemia was not due to a defect of the LDL-receptor gene. In a
      normal population PvuII RFLP account for 9.6% of the total variance of the LDL
      cholesterol levels adjusted for confounding variables. The P2 allele was
      associated with lower LDL cholesterol concentrations (average excess -9.1 mg/dl).
      This finding allows us to presume there is a DNA sequence, close to the variable
      PvuII cutting site in intron 15, which could act as an enhancer of the LDL
      receptor gene expression.

PMID- 1354624
TI  - Apo C-II deficiency type Bari.
AB  - We formerly studied an Italian family with apo C-II deficiency. Two probands were
      homozygous for the defect (unmeasurable circulating apolipoprotein C-II and
      absence of C-II bands on immunoelectrophoresis). We documented the synthesis of
      the protein at the intestinal level in the probands with immunohistological
      techniques. With the purpose of investigating the molecular basis of the defect,
      Southern analysis, polymerase chain reaction (PCR) amplification and sequence
      analysis were carried out on one of the two cases. We identified a point mutation
      C to G transversion in the third exon of the gene causing a premature stop codon.
      Our hypothesis is that the truncated protein of 36 aa., instead of 79 aa., lacks
      its functional domain. This causes inefficiency in the activation of lipoprotein
      lipase (LPL) and the instability of the circulating molecule, which could have an
      higher catabolic rate compared to a normal protein. The faster disappearance from
      the circulating compartment make it unmeasurable. The mutation destroys a Rsa I
      site, present in the normal gene sequence. We suggest the use of this site for a
      rapid Restriction Fragment Length Polymorphism (RFLP) on PCR amplification
      products to screen this defect in the Italian population.

PMID- 1354626
TI  - Streptomyces lividans possesses a GroEL-like chaperonin.
AB  - Streptomyces lividans grown at 45 degrees C produces a GroEL-like chaperonin.
      This protein is specifically synthesized in bacterial cell cultures upon heat
      shock induction. It has a similar size (62 kDa) to the GroEL-like proteins from
      Escherichia coli and Bacillus subtilus and shows immunological cross-reaction
      with serum raised against GroEL from E. coli. The S. lividans 62-kDa protein
      assembles into oligomers around 20S that show a morphology consistent with a
      barrel showing six-fold and seven-fold symmetries as previously described in E.
      coli and B. subtilis.

PMID- 1354627
TI  - Latex hypersensitivity reactions despite prophylaxis.
AB  - Latex rubber hypersensitivity represents a significant problem facing the
      medical, surgical, radiologic, and dental professions. As a tertiary care center,
      the Childrens Hospital of Philadelphia has a large population of patients with
      spina bifida and complex genitourinary anomalies; a number of these children have
      latex rubber allergy, which may first present as intraoperative anaphylaxis.
      Although there is no substitute for complete antigen avoidance, all medical
      products containing latex rubber may not have suitable alternatives. Therefore,
      we have formulated a protocol to prevent perioperative reactions through the use
      of prophylactic medications and the limitation of latex exposure. This regimen
      includes steroids, antihistamines, and bronchodilators when indicated. In four
      children, prophylaxis failed perioperatively because of parenteral infusion of
      latex rubber proteins.

PMID- 1354628
TI  - [Are gestagens suitable for lowering the membrane potential of the uterine muscle
      and eliminating the need for beta-mimetics?].

PMID- 1354629
TI  - [In which pregnancy trimester is therapy with beta-mimetics of value? Beta
      receptor density in the course of pregnancy?].

PMID- 1354630
TI  - [Comparison of the effects of benzodiazepine and non-benzodiazepine anxiolytics
      on agonistic behavior in male mice].
AB  - The present study investigated whether there is any difference between the
      effects of benzodiazepine and non-benzodiazepine anxiolytics on agonistic
      behavior in male mice, using an ethopharmacological technique. Agonistic behavior
      was evoked using a resident-intruder paradigm. The effects of four doses of the
      following drugs were assessed in either resident or intruder mice: diazepam
      (vehicle, 1, 2.5 and 5 mg/kg, p.o.) and tandospirone (vehicle, 2.5, 5 and 10
      mg/kg, p.o.). Residents and intruders were drugged on alternate test days, and
      all animals received different sequences of each of the drug conditions according
      to a random schedule. The injection-test interval was 30 min. When a resident
      mice were treated with either diazepam or tandospirone, the frequency of attack
      bite was suppressed significantly in a dose-dependent manner. When intruder mice
      were treated with diazepam, attack bites by untreated residents were
      significantly increased, whereas tandospirone was ineffective. Although diazepam
      caused a significant decrease in both locomotion and rearing, tandospirone did
      not cause motor dysfunction. These evidence indicate that tandospirone, a 5-HT1A
      receptor agonist, has different pharmacological properties from diazepam.

PMID- 1354631
TI  - [Effects of IGN-2098, a new histamine H2-receptor antagonist, on gastric
      secretion and gastric and duodenal lesions induced in rats. Comparison with
      roxatidine].
AB  - A new compound, IGN-2098 [5,6-dimethyl-2-[4-<3-(1-piperidinomethyl) phenoxy>cis
      butenylamino]-4-(1H)-pyrimidone.2HCl], was found to be a potential histamine H2
      receptor antagonist in the guinea pig atrium. IGN-2098, given p.o., significantly
      and persistently (for more than 12 hr) inhibited the basal gastric secretion in
      pylorus-ligated rats. The agent also significantly inhibited the basal gastric
      secretion when given by the s.c.-, i.d.- or i.p.-route. Stimulated gastric
      secretion in fistula rats in response to histamine, carbachol or pentagastrin was
      also significantly inhibited with IGN-2098 given s.c. Pretreatment with IGN-2098
      (p.o.) significantly protected the gastric mucosa against pylorus ligation-,
      water-immersion stress-, histamine-, indomethacin-, HCl.aspirin-, and HCl.ethanol
      induced gastric lesions. In addition, the agent significantly protected the
      duodenal mucosa against mepirizole-induced ulcers. Based upon the ED50 values,
      the antisecretory effects on histamine, carbachol or pentagastrin-stimulated acid
      secretion were 6.0, 37.0 or 80 times more potent than roxatidine, respectively.
      As to the anti-lesion effects on HCl.aspirin-induced gastric lesions or
      mepirizole-induced duodenal ulcers, IGN-2098 was 8.1 or 14.8 times more potent
      than roxatidine, respectively. These results suggest that IGN-2098 will be a
      useful drug for the treatment of gastric and duodenal lesions in man.

PMID- 1354632
TI  - Importance of imidazoline receptors in the cardiovascular responses to clonidine
      and rilmenidine in conscious rabbits.
AB  - The present paper summarizes our studies concerning the involvement of
      imidazoline and alpha 2-adrenoceptors in the cardiovascular actions of centrally
      acting drugs rilmenidine, clonidine and methyldopa. We have found that they
      produce very similar cardiovascular autonomic effects which relate directly to
      the function of central monoamine neurotransmitters. They mimic certain elements
      of the noradrenergic neuron system in the central nervous system, in particular
      the brainstem actions which involve hypotension, bradycardia and resetting of the
      baroreceptor heart rate reflex. By contrast they turn off serotonergic pathways
      that are pressor, produce tachycardia and inhibit the baroreceptor heart rate
      reflex. Recent studies using specific receptors antagonist drugs idazoxan and 2
      methoxy-idazoxan indicate that in conscious rabbits the imidazoline receptor
      actions of rilmenidine is of primary importance at doses which would be
      considered clinically relevant. We further conclude that the alpha 2
      adrenoceptors and the imidazoline receptors are likely to be located in series
      i.e. along the same cardiovascular autonomic pathways in the brainstem but
      presumably at different sites.

PMID- 1354633
TI  - Clinical pharmacology of imidazolines and related compounds.

PMID- 1354636
TI  - Cell-cell interactions: clues to hepatocyte heterogeneity and beyond?

PMID- 1354634
TI  - Individualized treatment of duodenal ulcer disease. A pilot study.
AB  - A substantial number of duodenal ulcer (DU) patients relapse despite maintenance
      treatment with antisecretory drugs. The influence of certain risk factors and the
      heterogeneity of the disease could explain such behavior. The present
      prospective, open study compares the one-year clinical outcome (with upper GI
      endoscopy at the beginning of the study, at 6 and 12 months, and at every
      symptomatic relapse) of four groups of DU subjects, consecutively recruited from
      December 1987 to December 1988, separated in accordance with whether or not a
      bleeding DU episode had previously occurred, and whether or not an evaluation of
      gastric acid secretion had been made. Thus, Group I (17 patients; 12 males, 5
      females) included heavy smokers and/or gastric acid hypersecretors; Group II (13
      patients; 12 males, 1 female) non- or light smokers non-hypersecretors; Group III
      (34 patients; 22 males, 12 females) subjects with unknown gastric acid secretion;
      Group IV (33 patients; 30 males, 3 females) previously bleeding DU patients. All
      patients, except those in Group II (who were left untreated), were given
      ranitidine 150 mg at bedtime. The outcome of Groups I+II was compared with that
      of Group III (considered as "standard therapy") and Group IV patients, the latter
      presumably with a low risk of relapse because of the low prevalence of smokers.
      STATISTICS: Chi-square test, Fisher's exact test, analysis of variance and the
      logrank test. During the year of follow-up, 27/97 patients withdrew from the
      study, while 18 had a DU relapse (remission rates 82.1% +/- 7.4% in Groups I+II,
      70.5% +/- 8.4% in Group III, 87.5% +/- 5.9% in Group IV).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1354635
TI  - Detection of circulating intercellular adhesion molecule-1 in chronic liver
      diseases.
AB  - The leucocyte adhesion molecule intercellular adhesion molecule-1 is induced on
      bile ducts in patients with primary biliary cirrhosis and primary sclerosing
      cholangitis and may be involved in targeting immune damage to these structures.
      It has recently been reported that, when activated, in vitro lymphocytes release
      a soluble form of intercellular adhesion molecule-1 that can also be detected in
      human serum. Because it is functionally active, this circulating intercellular
      adhesion molecule-1 might play a role in regulating inflammation by blocking
      adhesion. We used an enzyme-linked immunosorbent assay to detect circulating
      intercellular adhesion molecule-1 in the serum of patients with primary biliary
      cirrhosis and primary sclerosing cholangitis. Levels of circulating intercellular
      adhesion molecule-1 were markedly elevated in primary biliary cirrhosis and
      primary sclerosing cholangitis when compared with other chronic liver diseases.
      Circulating intercellular adhesion molecule-1 is probably derived from activated
      lymphocytes rather than from bile ducts because biliary epithelial cells from
      patients with primary biliary cirrhosis did not release circulating intercellular
      adhesion molecule-1 when stimulated to express the membrane-bound molecule in
      vitro. These studies are the first to demonstrate circulating intercellular
      adhesion molecule-1 in chronic inflammatory diseases that are characterized by
      strong tissue expression of intercellular adhesion molecule-1 and as such suggest
      a potential immunoregulatory role for circulating adhesion molecules. The very
      high levels detected in primary biliary cirrhosis and primary sclerosing
      cholangitis probably reflect lymphocyte activation, which is further evidence of
      immune pathogeneses for these diseases.

PMID- 1354637
TI  - A high-resolution cytogenetic map of human chromosome 3: localization of 291 new
      cosmid markers by direct R-banding fluorescence in situ hybridization.
AB  - We localized 291 new cosmid markers (including 65 RFLPs) on human chromosome 3 by
      direct R-banding fluorescence in situ hybridization. This system, which is based
      on fluorescence in situ hybridization combined with replicated prometaphase R
      bands, allows the direct visualization of signals on R-banded prometaphases
      stained with propidium iodide and provides a more rapid and efficient method for
      genome mapping of cosmid clones. The signals of 291 markers examined here were
      localized preferentially to R-positive bands throughout chromosome 3. The
      detailed map positions of 366 clones and the characterization of 142 RFLPs,
      including the preliminary data reported by Yamakawa et al. (1991, Genomics 9: 536
      543; and 11: 565-572), are summarized. This high-resolution cytogenetic map
      (average distance of 0.58 Mb), in conjunction with a genetic linkage map, can
      facilitate the analysis of chromosomal and molecular aberrations in genetic
      diseases and cancers. Furthermore, these mapping data will provide many useful
      landmarks for the construction of contig maps of chromosome 3.

PMID- 1354638
TI  - An interspecific linkage map of mouse chromosome 15 positioned with respect to
      the centromere.
AB  - We have used an interspecific backcross between C57BL/6J and Mus spretus to
      derive a molecular genetic linkage map of chromosome 15 that includes 25
      molecular markers and spans 93% of the estimated length of chromosome 15. Using a
      second interspecific backcross that was analyzed with a centromere-specific
      marker, we were also able to position our map with respect to the chromosome 15
      centromere. This map provides molecular access to many discrete regions on
      chromosome 15, thus providing a framework for establishing relationships between
      cloned DNA markers and known mouse mutations and for identifying homologous genes
      in mice and humans that may be involved in disease.

PMID- 1354640
TI  - A multipoint genetic linkage map of mouse chromosome 18.
AB  - We have mapped 13 loci on mouse Chromosome 18 by Southern blot analysis of
      restriction fragment length polymorphisms among progeny from an interspecific
      backcross: (C57BL/6J X Mus spretus) X M. spretus. Complete haplotype analysis of
      136 of these progeny was used to establish gene order and estimate genetic
      distances between loci. The gene order (from centromere to telomere) and
      recombination distances (in centimorgans) were as follows: PGK-1rs5-4.3-Tpi-10
      11.8-(Egr-1, Hmg17-rs9)-2.1-Fgfa-2.2-Grl-1-10.1-(Cdx-1, Csfmr, Pdgfrb, Pdea,
      Rps14)-2.1-Adrb-2-22.9-Mbp. Pgk-1rs5, Tpi-10, Hmg17-rs9, and Rps14 had not been
      previously mapped in the mouse; Egr-1 had only been syntenically assigned to
      mouse Chr 18. Nine of the loci, spanning 18 cM, have homologs on the distal long
      arm of human Chr5--a region rich in genes encoding growth factors and receptors.
      An additional previously unmapped gene, Drd-1, predicted to be on mouse Chr 18
      based on its human chromosomal location, was mapped to the middle region of mouse
      Chr 13.

PMID- 1354639
TI  - Isolation of 1001 new markers from human chromosome 11, excluding the region of
      11p13-p15.5, and their sublocalization by a new series of radiation-reduced
      somatic cell hybrids.
AB  - The determination of the physical map of human chromosome 11 will require more
      clones than are currently available. We have isolated an additional 1001 new
      markers in a bacteriophage vector from a somatic cell hybrid cell line that
      contains most of chromosome 11, except the middle of the short arm. These markers
      were localized to five different regions, 11p15-pter, 11p12-cen, 11q11-q14, 11q14
      q23, and 11q23-qter, by a panel of previously characterized somatic cell hybrids.
      The region 11q11-14 harbors genes that have been shown to be important in breast
      cancer, B-cell lymphomas, centrocytic lymphomas, asthma, and multiple endocrine
      neoplasia, type 1 (MEN1). To determine the positions of the recombinant clones
      located there, we developed a new series of radiation-reduced somatic cell
      hybrids. These hybrids, together with those previously characterized, allowed us
      to map the 11q11-q14 markers into 11 separate segregation groups.

PMID- 1354641
TI  - DLX2 (TES1), a homeobox gene of the Distal-less family, assigned to conserved
      regions on human and mouse chromosomes 2.
AB  - Dlx-2 (also called Tes-1), a mammalian member of the Distal-less family of
      homeobox genes, is expressed during murine fetal development in spatially
      restricted domains of the forebrain. Searching for a candidate neurological
      mutation that might involve this gene, we have assigned the human and mouse loci
      to regions of conserved synteny on human chromosome 2, region cen--q33, and mouse
      chromosome 2 by Southern analysis of somatic cell hybrid lines. An EcoRI
      dimorphism, discovered in common inbred laboratory strains, was used for
      recombinant inbred strain mapping. The results place Dlx-2/Tes-1 near the Hox-4
      cluster on mouse chromosome 2.

PMID- 1354642
TI  - Polymorphisms and deduced amino acid substitutions in the coding sequence of the
      ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia.
AB  - Twenty-one polymorphic sequence variants of the RYR1 gene, including 13
      restriction fragment length polymorphisms (RFLPs), were identified by sequence
      analysis of human ryanodine receptor (RYR1) cDNAs from three individuals
      predisposed to malignant hyperthermia (MH). All RFLPs were detectable in PCR
      amplified products, and their segregation was consistent with our initial finding
      of linkage to MH in the nine families previously informative for one or more
      intragenic markers (MacLennan et al., 1990, Nature 343:559-561). Four amino acid
      substitutions were identified in the study: Arg for Gly248, Cys for Arg470, Leu
      for Pro1785, and Cys for Gly2059. Of 45 families tested, a single family
      presented the Arg for Gly248 substitution where it segregated with malignant
      hyperthermia, making it a candidate mutation for predisposition to MH in man. The
      other three polymorphic substitutions failed to segregate with malignant
      hyperthermia in those families in which they occurred, implying that they
      represent polymorphisms with little or no effect on the function of the RYR1
      gene.

PMID- 1354643
TI  - Isolation and mapping of 88 new RFLP markers on human chromosome 8.
AB  - To obtain new RFLP markers for construction of a high-resolution map of human
      chromosome 8, a cosmid library was constructed from a somatic hybrid cell that
      contained chromosome 8 as the only human component in mouse genomic background.
      Eighty-eight new RFLP markers were isolated and characterized, and 71 of them
      were sublocalized to chromosomal bands by fluorescent in situ hybridization
      (FISH). Of these, 36 were localized to the short arm, 34 to the long arm, and 1
      to the centromeric region. Five markers defined VNTR loci. This work represents
      the first extensive isolation and physical mapping of RFLP markers on human
      chromosome 8. These new markers will serve as useful resources for linkage
      mapping of loci for inherited diseases and for efforts to identify a putative
      tumor suppressor gene(s) on chromosome 8.

PMID- 1354644
TI  - A molecular genetic linkage map of mouse chromosome 18 reveals extensive linkage
      conservation with human chromosomes 5 and 18.
AB  - An interspecific backcross between C57BL/6J and Mus spretus was used to generate
      a molecular genetic linkage map of mouse chromosome 18 that includes 23 molecular
      markers and spans approximately 86% of the estimated length of the chromosome.
      The Apc, Camk2a, D18Fcr1, D18Fcr2, D18Leh1, D18Leh2, Dcc, Emb-rs3, Fgfa, Fim
      2/Csfmr, Gnal, Grl-1, Grp, Hk-1rs1, Ii, Kns, Lmnb, Mbp, Mcc, Mtv-38, Palb,
      Pdgfrb, and Tpl-2 genes were mapped relative to each other in one interspecific
      backcross. A second interspecific backcross and a centromere-specific DNA
      satellite probe were used to determine the distance of the most proximal
      chromosome 18 marker to the centromere. The interspecific map extends the known
      regions of linkage homology between mouse chromosome 18 and human chromosomes 5
      and 18 and identifies a new homology segment with human chromosome 10p. It also
      provides molecular access to many regions of mouse chromosome 18 for the first
      time.

PMID- 1354645
TI  - Extension of the physical map in the region of the mouse X chromosome homologous
      to human Xq28 and identification of an exception to conserved linkage.
AB  - We have extended our pulsed-field gel map of the region of the mouse X chromosome
      homologous to human Xq28 to include the loci Gdx (DXS254Eh), P3 (DXS253Eh), G6pd,
      Cf-8, and F8a. Gdx, P3, and G6pd are demonstrated to be physically linked to the
      X-linked visual pigment locus (Rsvp) within a maximal distance of 340 kb, while
      G6pd and Cf-8 are approximately 900 kb apart. These studies favor a gene order of
      cen-Rsvp-Gdx-P3-G6pd-(Cf-8)-tel and extend the physical map of this region to 5
      million bp. In conjunction with previous physical mapping studies in both mouse
      and human, the results suggest conserved linkage for loci in this region of the
      mouse X chromosome and human Xq28. However, employing pulsed-field gel
      electrophoresis and genetic pedigree analysis of interspecific backcross progeny,
      we have found close linkage of a clone encoding a mouse homolog for human factor
      VIII-associated gene A (F8A) to DXPas8, thus revealing the first exception to
      conserved gene order between murine and human loci in the region.

PMID- 1354647
TI  - Regional localization of three convertases, PC1 (Nec-1), PC2 (Nec-2), and furin
      (Fur), on mouse chromosomes.
AB  - The genes for three convertases, PC1 (Nec-1), PC2 (Nec-2), and furin (Fur), have
      been regionally localized on chromosomes 13, 2, and 7, respectively, by
      interspecific backcross analysis. These results refine previous localizations by
      in situ hybridization as well as confirm and extend known regions of homology
      between mouse and human chromosomes.

PMID- 1354646
TI  - Identification of 57 conventional RFLP and 6 VNTR systems with 32 DNA clones on
      chromosome 11p15.
AB  - Fifty-four clones containing human inserts were selected from a cosmid library
      constructed from a somatic cell hybrid containing chromosome 11p15.3-p15.5 as its
      only human complement. In 32 of these clones, 63 polymorphic systems were
      identified with a panel of restriction enzymes: 57 conventional RFLP systems and
      6 highly polymorphic VNTR systems. Although we examined the cosmid with only
      seven enzymes, 18 clones (including 6 VNTRs) were polymorphic with three or more
      enzymes. The results suggested that DNA sequences on the peritelomeric region of
      chromosome 11p tend to be highly variable. Because these markers are highly
      informative, they will be excellent resources for investigations of hereditary
      diseases and tumor suppressor genes in this region of chromosome 11.

PMID- 1354648
TI  - Assignment of the gene coding for hepatocyte growth factor-like protein to mouse
      chromosome 9.
AB  - The gene coding for hepatocyte growth factor-like protein has been localized to
      mouse chromosome 9 at a locus (Hgfl) distal to the Trf locus. The likely gene
      order in this region is centromere-Trf-Gnai-2-Hgfl-Cck. The region surrounding
      the Hgfl locus shows homology of syntenty to band p21 on human chromosome 3.

PMID- 1354649
TI  - Blood glucose response to stress hormone exposure in healthy man and insulin
      dependent diabetic patients: prediction by computer modeling.
AB  - To establish a qualitative and quantitative model of blood glucose response to
      stress hormone exposure, healthy subjects (HS) on and off somatostatin (250
      micrograms/h) as well as insulin dependent diabetic patients were infused with
      either epinephrine (E), glucagon (G), cortisol (F), growth hormone (GH) or with a
      cocktail of these hormones raising plasma stress hormones to values seen in
      severe diabetic ketoacidosis. The developed input/output model consists of two
      submodels interconnected in series plus two additional submodels for correction
      of gains describing both sensitivity of tissue response and utilisation as well
      as provision of glucose. It was shown and confirmed experimentally that blood
      glucose response to stress hormones was essentially nonlinear. Furthermore, the
      mathematical models for healthy subjects and for insulin dependent diabetic
      patients proved to be of the same structure and differed only in the values of
      some typical parameters. The model raises the possibility to describe and in part
      to predict blood glucose response to stress hormone exposure in healthy man and
      insulin dependent diabetic patients.

PMID- 1354650
TI  - Expression of cytokines by recombinant vaccinia viruses: a model for studying
      cytokines in virus infections in vivo.

PMID- 1354652
TI  - The importance of Th2 cytokines in protective immunity to nematodes.

PMID- 1354651
TI  - Role of T-cell derived cytokines in the downregulation of immune responses in
      parasitic and retroviral infection.
AB  - Parasitic infection is frequently accompanied by a downregulation in host cell
      mediated immunity. Recent studies suggest that this modulation of helper T cells
      and effector cell function can at least in part be attributed to the action of a
      set of inhibitory cytokines produced by T lymphocytes as well as by a number of
      other cell types. The best characterized of these inhibitory lymphokines are IL
      4, IL-10 and TGF-beta. Interestingly, both IL-4 and IL-10 are produced by the Th2
      but not the Th1 subset of CD4+ helper cells. The former subset dominates in many
      situations of chronic or exacerbated parasitic infection and is thought to
      suppress Th1 function as a consequence of the cross-regulatory activity of these
      two cytokines. The latter hypothesis is supported by recent experiments
      demonstrating that mAb-mediated neutralization of IL-10 reverses suppressed IFN
      gamma responses and/or disease susceptibility in mice with parasitic infections.
      In vivo neutralization of TGF-beta has also been reported to increase host
      resistance to parasite challenge. In addition to suppressing T-cell
      differentiation, function or proliferation, IL-4, IL-10 and TGF-beta each inhibit
      the ability of IFN-gamma to activate macrophages for killing of both
      intracellular and extracellular parasites. Moreover, the three cytokines are able
      to synergize with each other in downregulating these parasiticidal effects.
      Interestingly, each of the cytokines inhibits the production of reactive nitrogen
      oxides, an effector mechanism previously demonstrated to play a major role in
      parasite killing by activated macrophages. In the case of IL-10, this suppression
      of nitrogen oxide production appears to result from an inhibition of TNF-alpha
      synthesis leading to defective macrophage stimulation. While distant from
      parasites in their biology and phylogeny, some retroviruses also appear to induce
      an over-production in downregulatory cytokines which is closely associated with
      the onset of immunodeficiency. Thus, in an animal model involving infection of
      mice with LP-BM5 MuLV and in human HIV infection, Th2 (IL-10 and/or IL-4)
      cytokine synthesis is increased while Th1 (IFN-gamma and/or IL-2) cytokine
      production is suppressed. These observations suggest that cytokine-mediated cross
      regulation may play a role in the pathogenesis of acquired immune deficiency
      disease, contributing both to the progression of retroviral infection and the
      increase in susceptibility to opportunistic infections and malignancy.
      Observations of similar cytokine cross-regulatory activities in organisms as
      diverse as helminths, protozoa and retroviruses predict that comparable
      mechanisms may operate in a wide variety of infectious diseases.

PMID- 1354653
TI  - Effect of organophosphate pesticides on glutaminase synthetase activity in rat
      brain.
AB  - Of the organophosphate pesticides studied, dichlorvos inhibited significantly
      both, phosphate-activated glutaminase and alpha-keto acid-activated glutaminase,
      while monocorotophos inhibited moderately alpha-keto acid activated glutaminase
      in rat brain. Phosphamidon inhibited glutamine synthetase activity negligibly.

PMID- 1354654
TI  - Occurrence of colonization factor antigens I & II in enterotoxigenic Escherichia
      coli associated diarrhoea in Iran & correlation with severity of disease.
AB  - The occurrence of colonization factor antigens I and II (CFA/I and II) and type 1
      somatic pili was investigated in 197 enterotoxigenic Esch. coli (ETEC) isolated
      from 197 patients of diarrhoea (aged under 3 yr) during February 1985 to March
      1986 in Tehran, Iran. Among ETEC strains, 154 strains were heat-stable
      enterotoxin (ST) producers, 27 strains were heat-labile enterotoxin (LT)
      producers, and 16 strains produced both toxins. Sixty five (33%) strains showed
      mannose-resistant haemagglutination (MRHA) of human and/or bovine erythrocytes;
      of these, 51 (86%) strains were positive for CFA/I and II. Seventy one (36%)
      strains also exhibited type 1 somatic pili. CFA/I was found in 4 (15%) LT
      producing, 24 (16%) ST producing, and 2 (13%) LT/ST producing strains. In
      contrast, CFA/II was only found in ST producing strains (17 strains) and those
      producing both toxins (4 strains). Patients having CFAs-positive ETEC strains had
      a significantly (P less than 0.001) higher number of stool evacuation per day and
      a longer duration of diarrhoea than those having CFAs-negative strains. Fifty
      nine patients had mixed infections of ETEC strains and other enteropathogens.
      CFA/I or II (CFAs)-positive and CFAs-negative ETEC strains were found in 17 and
      42 patients with mixed infections respectively. The mean number of stool
      evacuations per day was much higher in patients with ETEC and rotavirus than
      those with only ETEC infection (P less than 0.001). However, severity of the
      disease was not affected by the presence or absence of CFA/I or II in ETEC
      strains found in these patients.

PMID- 1354655
TI  - Undescended testis: evaluation by magnetic resonance imaging.
AB  - We describe our experience of prospective magnetic resonance imaging (MRI) study
      in patients of undescended testis, with a 1.5 T equipment using body coil. There
      were thirty two patients, aged 1.5 to 14 years with a mean age of nine years.
      Surgical follow up was obtained for thirty one patients. We were able to indicate
      the position of 26 testes in 22 patients and absence of five testes in three
      patients. MRI was falsely positive and negative for five and two testes,
      respectively. Testicular tissue at ectopic site was identified by presence of
      characteristic signal intensity pattern, mediastinum testis and its location
      along empty spermatic canal in cases of inguinal testis either singly or in
      combination. MRI was able to detect atrophic changes in four testes, confirmed on
      surgery. The study concludes that MR imaging is useful in the localization and
      tissue characterization of a non palpable testis. However, it is not sensitive
      enough for complete exclusion of the diagnosis of an undescended testis. Thus a
      surgical or laproscopic exploration may be needed further in selective cases for
      the management of patient.

PMID- 1354658
TI  - Hypercholesterolemia in a young woman.

PMID- 1354656
TI  - Myocardial anti-ischemic characteristics of a novel class of beta-adrenoceptor
      blockers.
AB  - The effect of different beta-adrenoceptor blockers on free radical-mediated
      cardiac membrane lipid peroxidation (CMLP) was compared to their beta-blocking
      potency (pA2). CMLP was determined by the measurement of malondialdehyde (MDA)
      formation in rat cardiac membrane homogenates exposed to a free radical
      generating system (FeCL3/ADP/DHF) in the presence or absence of the beta
      adrenoceptor blockers (1-1,000 microM). beta-adrenoceptor blocking potency (pA2)
      was determined using guinea pig right atria stimulated with isoproterenol. The
      catechol containing beta-blocker (DCC-10255) was shown to be a potent inhibitor
      of CMLP via an iron-dependent mechanism. On the other hand, the non-catechol beta
      adrenoceptor blocker, timolol, was shown to be a weak inhibitor of CMLP.
      Furthermore, dl- and d-propranolol were active and equipotent though less potent
      than DCC-10255 in inhibiting CMLP. The myocardial cytoprotective efficacy for
      catechol and non-catechol beta-adrenoceptor blockers was evaluated in an isolated
      rat myocyte model. It was demonstrated that catechol-containing agents with
      either strong or weak beta-adrenoceptor blockade possess a relatively potent in
      vitro antioxidant and myocardial cytoprotective efficacy against free radical
      mediated CMLP and myocyte injury, respectively. It is concluded that the
      inhibition of CMLP by beta-adrenoceptor blockers is independent of their beta
      adrenoceptor blockade.

PMID- 1354659
TI  - Postmenopausal hormone replacement in a perimenopausal woman.

PMID- 1354657
TI  - Comparative review of third-generation progestins.
AB  - Desogestrel, gestodene, and norgestimate represent a new generation of progestins
      designed for use in oral contraceptives. A high degree of efficacy has been
      retained in these progestins, and the adverse metabolic impact exhibited by older
      progestins has been reduced considerably. The clinical profile of each progestin,
      as it is marketed in Europe in combination with ethinyl estradiol, is reviewed.
      Direct comparisons are made whenever applicable. The major advantages of these
      formulations over the older combined oral contraceptives are that they have less
      effect on lipid metabolism and on carbohydrate metabolism, and they are less
      androgenic. The clinical implications of these findings are discussed.

PMID- 1354660
TI  - Older patients and oral contraceptives.

PMID- 1354661
TI  - Women, lipoproteins, and cardiovascular disease risk.
AB  - Women, like men, are susceptible to coronary atherosclerosis. Like men, more
      women die of heart disease than all forms of cancer combined. Coronary
      atherosclerosis is the result of the interplay of a number of factors, the most
      important of which are abnormal levels of circulating lipoproteins. As more has
      become known about the mechanisms by which abnormal levels of circulating
      lipoproteins promote atherosclerosis, certain risk factors have emerged as
      concerns for women, including: (1) diabetes mellitus as a risk factor, perhaps
      through its more profound effects on circulating lipoproteins; (2) serum
      triglyceride levels, and (3) changes in high-density lipoprotein cholesterol. The
      widespread use of exogenous hormones in women as both oral contraceptives and
      postmenopausal hormone replacement may also play a role in developing
      atherosclerosis. In general, estrogen affects circulating lipoprotein levels
      favorably, whereas progestins have the opposite effect. The effects of
      estrogen/progestin combinations in either oral contraceptives or postmenopausal
      hormone replacement will depend on the relative dose and potency of each of these
      constituents. Epidemiologic studies indicate that the use of oral contraceptives
      has no profound effect on the long-term risk of heart disease, whereas unopposed
      estrogen (without progestin) in postmenopausal hormone replacement therapy may
      lower that risk considerably. Recent U.S. and European guidelines for the
      detection, evaluation, and treatment of hypercholesterolemia in adults make it
      imperative that obstetrician-gynecologists, in their dual role as primary-care
      physicians and prescribers of exogenous hormones, be aware of and informed about
      the relationship between circulating lipids and lipoproteins and coronary heart
      disease in women.

PMID- 1354662
TI  - Diabetes mellitus, hypertriglyceridemia, and heart disease risk in women.
AB  - Coronary heart disease is the most common cause of death in men and women in
      developed countries. Three primary risk factors--high serum cholesterol
      concentration, hypertension, and cigarette smoking--are known to increase the
      risk in both men and women more or less equally, although the latter two risk
      factors are a somewhat greater risk to men. This paper reviews two additional
      risk factors whose impact may be greater in women: diabetes and
      hypertriglyceridemia. Understanding how diabetes and hypertriglyceridemia act
      differently in women may explain some of the sex differences in the risk of heart
      disease.

PMID- 1354663
TI  - Mechanism of action/effects of androgens on lipid metabolism.
AB  - The strongest predictors of cardiovascular disease in women have been shown to be
      diabetes, high blood pressure, cigarette smoking, and, to a lesser degree,
      hypertriglyceridemia. The difference in risk between men and premenopausal women
      has been explained by the following widely held hypothesis: androgens lower
      plasma concentrations of high-density lipoprotein (HDL), particularly the HDL-2
      subfraction, and increase plasma concentrations of low-density lipoprotein (LDL).
      In contrast, estrogens have the opposite effect, raising plasma concentrations of
      HDL, particularly HDL-2, and lowering plasma concentrations of LDL. After the
      menopause, it is believed that the protective effect of estrogens in women is
      lost and the incidence of heart disease rises to equal that in men. This paper
      provides a brief review of the effect of endogenous and exogenous androgens on
      lipoprotein metabolism in men and women, and considers the relevance of these
      findings to the choice of progestogens used in oral contraceptive preparations.

PMID- 1354664
TI  - Steroids and lipid metabolism: mechanism of action.
AB  - The effects of steroids on hepatic metabolism depend on the preexisting metabolic
      status of the individual and the structure, dosage, and, to a certain extent, the
      route of administration of the steroid compound. Oral administration of synthetic
      estrogen causes an increase in hepatic production of very-low-density lipoprotein
      (causing in turn an increase in triglyceride levels), an increase in coagulation
      factors, and an increase in high-density-lipoprotein cholesterol, which is
      related to a decrease in hepatic lipase activity. Parenteral administration of
      estrogen does not appear to cause any such modification. The effects of
      progestogen on hepatic metabolism are dependent on the androgenic activity of the
      specific progestogen administered. A progestogen with greater androgenic activity
      causes a decrease in high-density-lipoprotein cholesterol, which is related to an
      increase in hepatic lipase activity. This article reviews the effects of steroids
      (both estrogens and progestogens) on the mechanisms of action in lipid
      metabolism.

PMID- 1354665
TI  - Effects of hormone replacement therapy.
AB  - According to the World Health Organization, the global life expectancy at birth
      was 55 years in 1974, will be 63 years in 2000, and will be close to 70 years in
      the year 2025. By the year 2025, approximately 20% of the world's population will
      be more than 60 years old, and the problems associated with hormonal changes
      become significant with more than one third of a woman's expected life
      concentrated in the postmenopausal years. Much evidence suggests that the use of
      postmenopausal estrogen substantially reduces the morbidity and mortality of
      coronary heart disease, and to date, low-dose estrogen therapy is the single most
      effective method for prevention of osteoporosis. However, only hysterectomized
      women can use estrogen alone because of the risk of endometrial cancer associated
      with unopposed estrogen therapy. Thus, women with an intact uterus must use
      estrogen in combination with progestogen to avoid this risk, but the different
      progestogens may variously modify the beneficial effects of estrogen on
      lipoproteins, and, ultimately, coronary heart disease. Although hormone
      replacement therapy during menopause soon will be one of the major areas of
      preventive medicine, the effects of estrogen in combination with different
      progestins on coronary heart disease, blood pressure, blood coagulation, bone
      density, and the central nervous system have not been investigated adequately.
      This paper reviews the current knowledge of known or suspected effects.

PMID- 1354666
TI  - Ganglia within the gut, heart, urinary bladder, and airways: studies in tissue
      culture.

PMID- 1354667
TI  - New developments in magnetic resonance contrast media. A global perspective on
      Gadoteridol. Symposium proceedings. San Francisco, August 16, 1991.

PMID- 1354669
TI  - Intravenous recombinant secretory leukoprotease inhibitor augments antineutrophil
      elastase defense.
AB  - Secretory leukoprotease inhibitor (SLPI), a 12-kDa serine antiprotease, normally
      protects the upper airway epithelial surface from attack by neutrophil elastase
      (NE). In the context that a variety of inflammatory lung diseases are
      characterized by large neutrophil burdens with resultant high levels of NE in the
      lung, recombinant SLPI (rSLPI), a molecule identical to natural SLPI, may be an
      effective means to augment the anti-NE protective screen of the lung. To
      determine whether intravenous rSLPI will augment respiratory tract and epithelial
      surface levels of SLPI and anti-NE capacity, rSLPI was administered intravenously
      to sheep and SLPI levels were quantified in plasma, lung lymph (as a measure of
      lung interstitial levels), lung epithelial lining fluid (ELF), and urine. rSLPI
      (1 g) was administered over 10 min, and after 30 min plasma levels of SLPI were 8
      microM and decreased with a half-life of 1.8 h. Lymph SLPI levels paralleled the
      plasma levels: 4 h after infusion the lymph-to-plasma ratio was 0.8. ELF SLPI
      levels paralleled the lymph levels: 4 h after infusion the ELF-to-lymph ratio was
      0.3. Western analysis demonstrated intact SLPI in lymph and ELF, and functional
      analysis showed increases in lymph and ELF anti-NE capacity that paralleled the
      levels of SLPI. As might be expected from a protein with a molecular mass of 12
      kDa, urine excretion was high, with 20% of the SLPI excreted over 5 h. However,
      if the rate of infusion was slowed, SLPI excretion decreased significantly, with
      a 3-h infusion associated with 9% excretion and a 12-h infusion associated with
      less than 0.2% excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354668
TI  - Augmentation by bispecific F(ab')2 reactive with P-glycoprotein and CD3 of
      cytotoxicity of human effector cells on P-glycoprotein positive human renal
      cancer cells.
AB  - A bispecific F(ba')2 was constructed that was composed of two Fab fragments, one
      derived from anti-CD3 monoclonal antibody (mAb) (OKT3) and the other from anti P
      glycoprotein mAb (MRK 16). This bispecific F(ab')2 enhanced the binding and
      cytotoxicity of human peripheral blood mononuclear cells (PBMCs) on P
      glycoprotein-positive human kidney cancer cells (ADMHK/E). It had no effect on
      the cytotoxicity of PBMCs on P-glycoprotein-negative HK/E cells [long-term
      cultured HK/E (LCHK/E)]. Control F(ab')2 composed of OKT3 or MRK16 alone did not
      influence the cytotoxicity of PBMCs on ADMHK/E cells. These findings suggest that
      the MRK16-OKT3 bispecific F(ab')2 may be therapeutically beneficial in treatment
      of human multidrug-resistant cancers.

PMID- 1354670
TI  - Characterization of a simian virus 40-transformed human podocyte cell line
      producing type IV collagen and exhibiting polarized response to atrial
      natriuretic peptide.
AB  - Biology of glomerular visceral epithelial cells ("podocytes") and their role in
      inflammatory process remain obscure, partly because of the lack of well
      differentiated podocyte cultures. We have established a human cell line by
      transfecting with a replication-defective SV40 plasmid (pSVHB1), a primary
      culture of podocytes derived from an enriched preparation of unencapsulated
      glomeruli free of tubule and Bowman's capsule contaminants. Podocyte specificity
      of the primary culture was assessed by a dual immunomorphological and functional
      approach. The resulting cell line (HGVEC.SV1) was cloned and the clonal cells
      were adapted to hormonally defined medium supplemented with only 2% newborn
      bovine serum. Clone A4 has been exhibiting over 35 passages, a combination of
      markers unique to podocytes, including expression of vimentin, podocalyxin,
      ectoenzymes (CALLA antigen and mRNA), heparan-sulfate proteoglycans (molecular
      mass of core protein = 75 kDa), and production of type IV collagen (alpha 1 and
      alpha 5 chains) established by immunoprecipitation and Northern blot analysis.
      Cytokeratin was detected in rare cellular foci and the search of Von Willebrand
      factor was negative. This clonal cell line has been used to demonstrate: (1) that
      human podocytes are highly sensitive to atrial natriuretic peptide (ANP) which
      induced a dose-dependent increase in cGMP production (x20 at 0.5 microM ANP), and
      (2) that secretion of ANP-stimulated cGMP is dramatically polarized as 93% of
      extracellular cGMP were released in the apical medium when filter-grown HGVEC.
      SV1A4 cells were stimulated at their basal pole.

PMID- 1354671
TI  - Restoration of proliferating cell nuclear antigen (PCNA) complex formation in
      xeroderma pigmentosum group A cells following cis-diamminedichloroplatinum (II)
      treatment by cell fusion with normal cells.
AB  - We examined the role of the factor deficient in xeroderma pigmentosum group A (XP
      A) cells in the formation of proliferating cell nuclear antigen (PCNA) complex
      with DNA in the DNA repair process in human fibroblasts following cis
      diamminedichloroplatinum (CDDP)-treatment. Immunofluorescence staining after
      methanol fixation was used to detect the PCNA complex formation. When quiescent
      normal cells were PCNA-stained at 3 h after 100 microM CDDP treatment for 1 h,
      almost all nuclei of the cells showed a punctuated staining pattern. On the other
      hand, nuclei of XP-A cells were not stained. These results were the same with the
      findings following 10J/m2 of ultraviolet light (UV)-irradiation. The quantitative
      analysis of the PCNA immunofluorescence intensity of normal cells revealed that
      the mean intensity was increased by 4.8 times by the CDDP-treatment and 6.1 times
      by the UV-irradiation, compared with that of untreated cells. The intensities
      among nuclei ranged widely in both treatments. In contrast, the mean intensity
      was not increased in XP-A cells by the same treatments. However, when XP-A cells
      were fused with normal cells with polyethylene glycol (PEG) treatment, the nuclei
      of the XP-A cells showed positive PCNA-staining following CDDP-treatment or UV
      irradiation in almost all cases. These results suggest that the PCNA complex
      formation may play a role in the DNA repair process after the step where the
      factor deficient in XP-A cells is involved following CDDP-treatment as well as
      following UV-irradiation.

PMID- 1354672
TI  - Conditions for assembly of tubulin-based structures in unfertilized sea urchin
      eggs. Spirals, monasters and cytasters.
AB  - Cytasters were induced in the unfertilized eggs of the sea urchin Lytechinus
      pictus by two different methods: (1) treatment with hexylene glycol or taxol,
      which are known to lower the tubulin critical concentration in vitro, but do not
      activate the nuclear cycle, and (2) by raising the cytoplasmic pH from that of
      unfertilized cytoplasm to that of fertilized, which activated the nuclear cycle
      and initiated tubulin polymerization. In the unactivated eggs, with increasing
      concentrations of the inducing agents, temperature and duration of treatment,
      microtubule structures that formed showed a progression from loose microtubule
      networks and spiral arrays to tightly organized cytasters. In eggs incubated in
      sea water containing 2.5 or 10 mM ammonium acetate titrated with HCl or NaOH in
      steps from pH 5.0 to pH 9.0, the nuclear cycle and tubulin polymerization were
      initiated at about pH 7.0. The degree of development attainable after three hours
      was dependent on the pH, with spirals forming at the threshold level of pH 7.0,
      monasters at pH 7.5, and at pH 8.5 cells formed cytasters, multipolar spindles
      and even completed multipolar divisions. In unactivated eggs, tubulin was made
      available by lowering of the tubulin critical concentration; in activated eggs it
      was made available from some previously unavailable store. The evidence suggests
      that the amount of assembly-competent tubulin available, regardless of how it is
      made available, determines the type of structure that is formed, with microtubule
      bundles and spirals at the lower concentrations and functional cytasters at the
      upper. We also describe some details of cytaster formation, including the role of
      microtubule interactions and the movement of dense granules to the aster centers
      in hexylene glycol-treated eggs.

PMID- 1354673
TI  - Radioimmunoassay for the synthetic ergoline derivative cabergoline in biological
      fluids.
AB  - An antiserum against cabergoline, a powerful dopamine-agonist under clinical
      trials for the treatment of Parkinson's disease and hyperprolactinemia, has been
      raised in rabbits by immunization with an immunogen produced by conjugation of
      cabergoline to bovine serum albumin. The antiserum was able to bind a derivative
      of cabergoline labelled with tritium and was able to distinguish the drug
      molecule from some of its close related compounds and from other agents that
      could be simultaneously present in plasma from patients undergoing treatment with
      cabergoline. The antiserum and the tritium labelled hapten were used to develop a
      radioimmunoassay for cabergoline determination in human plasma and urine. A
      linear relationship between cabergoline added and % radioactivity bound was found
      in the range 1.9-500 pg/tube. The addition in the assay of 200 microliters human
      plasma or 25 microliters urine did not affect the specific and the non-specific
      binding of the radiolabelled hapten so enabling us to obtain a final sensitivity
      of about 12 pg/ml plasma and 120 pg/ml urine. The assay was validated in terms of
      reproducibility, precision and accuracy over the whole range of concentrations
      tested both in plasma and urine. The plasma concentrations at the steady state in
      a patient with Parkinson's disease who had received the drug at single oral daily
      doses of 3, 5 and 7 mg were determined using the assay.

PMID- 1354674
TI  - Immunoglobulins in milk from cows immunized with oral strains of Actinomyces,
      Prevotella, Porphyromonas, and Fusobacterium.
AB  - Immunization of pregnant cows with bacteria leads to the presence of high
      concentrations of specific antibodies in colostrum and milk. A total of 14 cows
      was immunized with single strains of heat-killed oral bacteria or pools of
      strains of Actinomyces, Porphyromonas, Prevotella, and Fusobacterium. Two cows
      were treated with adjuvant alone. The mean percentages of IgG1, IgG2, IgM, and
      IgA in all of the milks were 83.8, 3.8, 9.3, and 3.1, respectively. ELISA and
      whole cell agglutination assays demonstrated high titers in the milks from the
      cows immunized with either individual strains or the bacterial pools. The highest
      titers determined by ELISA belonged to the IgG1 isotype and in several milks were
      64-fold greater than titers in milk from cows treated with adjuvant alone. The
      concentrations of all antibodies and the titers determined by ELISA and whole
      cell agglutination assays markedly decreased from the first to the sixth
      milkings. The functional specificity of the antibodies was demonstrated by
      agglutination tests against a wide range of bacteria including members of
      Actinomyces, Fusobacterium, Porphyromonas, Prevotella, Streptococcus,
      Eubacterium, Propionibacterium, Peptostreptococcus, Bacteroides, Actinobacillus,
      Haemophilus, Capnocytophaga, and Wolinella. Minimal cross-reactions with bacteria
      in other genera were observed with all of the milks. High-titer milk preparations
      have been obtained from immunized cows, and the capacity of the bovine antibodies
      to agglutinate target bacteria indicates their potential usefulness in oral
      passive immunization studies.

PMID- 1354675
TI  - Common purslane: a source of omega-3 fatty acids and antioxidants.
AB  - omega-3 fatty acids, alpha-tocopherol, ascorbic acid, beta-carotene and
      glutathione determined in leaves of purslane (Portulaca oleracea), grown in both
      a controlled growth chamber and in the wild, were compared in composition to
      spinach. Leaves from both samples of purslane contained higher amounts of alpha
      linolenic acid (18:3w3) than did leaves of spinach. Chamber-grown purslane
      contained the highest amount of 18:3w3. Samples from the two kinds of purslane
      contained higher leaves of alpha-tocopherol, ascorbic acid and glutathione than
      did spinach. Chamber-grown purslane was richer in all three and the amount of
      alpha-tocopherol was seven times higher than that found in spinach, whereas
      spinach was slightly higher in beta-carotene. One hundred grams of fresh purslane
      leaves (one serving) contain about 300-400 mg of 18:3w3; 12.2 mg of alpha
      tocopherol; 26.6 mg of ascorbic acid; 1.9 mg of beta-carotene; and 14.8 mg of
      glutathione. We confirm that purslane is a nutritious food rich in omega-3 fatty
      acids and antioxidants.

PMID- 1354676
TI  - Long-term haemodynamic effects of a 4-week regimen of nipradilol, a new beta
      blocker with nitrovasodilating properties, in patients with portal hypertension
      due to cirrhosis. A comparative study with propranolol.
AB  - To study the long-term effects of pharmacological combination therapy, a
      comparison was made of the haemodynamic changes in patients with cirrhosis and
      portal hypertension following a 4-week treatment of propranolol or nipradilol, a
      new nonselective beta-blocker with nitrovasodilating effect. Nipradilol (12
      mg/dag, n = 12) significantly diminished wedged hepatic venous pressure (WHVP, 25
      +/- 16%), the hepatic venous pressure gradient (HVPG, 20 +/- 12%), and estimated
      hepatic blood flow (EHBF, 18 +/- 16%). Propranolol (30 mg/day, n = 11) also
      caused a significant reduction in WHVP (22 +/- 21%) and HVPG (24 +/- 21%), but
      not in EHBF. The percentage of portal pressure reduction and the frequency of
      nonresponders did not differ between the nipradilol and propranolol groups. Both
      agents reduced heart rate by approx. 20%. Nipradilol, however, did not cause a
      significant reduction in cardiac index (CI) versus a 14% reduction by
      propranolol. Pulmonary capillary wedge pressure and central venous pressure, an
      index of preload, were decreased slightly in the nipradilol group. When
      nonresponders were excluded, there was a significant correlation of the
      percentage of reduction between WHVP and CI or systemic vascular resistance, in
      the nipradilol group. These results indicate that nipradilol may have potent
      hypotensive effects on portal hypertension, similar but not superior to
      propranolol. Nipradilol, at the dosage used in the present study, did not appear
      to exert a nitrovasodilating effect to enhance the portal pressure reduction
      induced by beta-blocking action.

PMID- 1354677
TI  - Detection of proliferating cell nuclear antigen in diagnostic histopathology.
AB  - We describe the effects of tissue preservation, fixation time, and hydrolytic
      treatment on the detection of proliferating cell nuclear antigen (PCNA) by
      immunoperoxidase staining with three commercial anti-PCNA antibodies (19A2, 19F4,
      PC10). Our goal was to provide guidelines for PCNA immunohistochemistry in
      formalin-fixed, paraffin-embedded specimens. In proliferative cell compartments,
      nuclear staining was achieved with all three antibodies. In some cases PCNA was
      also expressed in non-proliferative, histologically normal tissues associated
      with tumors or other lesions elsewhere. In most autopsy specimens PNCA
      immunoreactivity was markedly diminished as compared with similar surgical
      specimens. Incubation overnight with primary antibody at 4 degrees C enhanced
      PCNA immunoreactivity over incubation at 42 degrees C for 45 min. Pre-treatment
      with 2 N HCl did not increase staining. Staining with the PC10 antibody was much
      better preserved than staining with the antibodies 19A2 and 19F4 after prolonged
      formalin fixation of surgical specimens and in tissues obtained at autopsy. With
      all three antibodies, however, PCNA immunoreactivity was well preserved during
      formalin fixation for 8-24 hr and during fixation delays for 8 hr at room
      temperature. This indicates that PCNA is stable under conditions routinely
      encountered in diagnostic surgical pathology and facilitates its potential use as
      a diagnostic proliferation marker.

PMID- 1354678
TI  - Generation and characterization of IL-2-activated veto cells.
AB  - The regulation of in vivo cytolytic response is important in a model of murine
      graft-vs-host disease induced by the injection of parental splenocytes into
      unirradiated B6D2F1 recipients. Injection of C57BL/6J spleen cells into B6D2F1
      recipients results in an acute form of graft-vs-host disease that is
      characterized by the presence of CTL and suppressor cells, runting, and
      occasionally death. In contrast, injection of DBA/2J spleen cells into B6D2F1
      recipients results in a chronic form of graft-vs-host disease that is
      characterized by the lack of in vivo CTL and hyperproduction of Ig and
      autoantibodies that results in an SLE-like syndrome. One reason for the lack of
      donor antirecipient CTL after injection of DBA/2J donor cells is that B6D2F1
      recipient cells functionally inactivate the donor DBA/2J CTL precursor cells by
      expressing veto activity. These B6D2F1 veto cells are radiosensitive, inhibited
      by anti-CD8 antibodies, found primarily in lymph nodes, and were further
      characterized by testing the response of these inhibitory cells to lymphokines.
      These studies indicate that IL-2 can potentiate the activity of the veto cells
      induced in vivo and veto cells with a similar phenotype can be generated by in
      vitro incubation of naive lymph node cells with IL-2. These cells have been
      designated as IL-2-activated veto cells or LAV cells. IL-2 did not increase
      inhibitory activity by increasing the number of CD8+ cells or the number of CD8
      molecules on the LAV cell surface but by altering the activation state of the LAV
      cell. The inhibitory capabilities of antibodies binding various cell surface
      molecules indicated that CD2 and intercellular adhesion molecule-1 molecules in
      addition to CD8 molecules played a role in the function of LAV cells.

PMID- 1354679
TI  - Fetal skin: a site of dendritic epidermal T cell development.
AB  - Thy-1 Ag and CD3-associated TCR-gamma (V gamma 3)/delta (V delta 1) are
      coexpressed on virtually all dendritic epidermal T cells (DETC) in the adult
      mouse. In contrast, day 16 fetal mouse skin contains small numbers of CD45+/Thy
      1+/CD3- but no CD3+ cells. To see whether the CD45+/Thy-1+/CD3- fetal skin cells
      can qualify as DETC precursors, we transplanted day 16 fetal skin of C57BL/6 (Thy
      1.2) mice onto adult B6Pl-Thy-1a (Thy-1.1) animals. At certain time points after
      transplantation, grafts were analyzed for the presence of Thy-1 and CD3/TCR Ag.
      Examination of the grafts, 4 days after transplantation, revealed the presence of
      few donor-type Thy-1.2+/CD3- and some Thy-1.2+/CD3+ epidermal cells of either
      round or dendritic configuration. At 10 weeks after transplantation, essentially
      all CD45+/Thy-1.2+ epidermal cells were anti-TCR V gamma 3 and anti-CD3-reactive,
      displayed a uniformly dendritic configuration, and, thus, represent DETC. Our
      assumption that CD45+/Thy-1+/CD3- cells are the only lymphocytes within day 16
      fetal skin gained additional support by the observations: 1) that unfractionated
      as well as anti-CD45 gated single cell suspensions prepared from day 16 fetal
      skin were consistently devoid of anti-CD3 epsilon and anti-TCR V gamma 3-reactive
      cells; and 2) that stimulation of these cell suspensions with either Con A plus
      IL-2 or IL-2 alone regularly resulted in the outgrowth of CD45+/Thy-1+/CD3-/TCR V
      gamma 3- cells, but never in the appearance of CD45+/Thy-1+/CD3+/TCR V gamma 3+
      cells. Our additional finding that Con A plus IL-2- or IL-2-stimulated day 16
      fetal skin cells and cell lines derived therefrom contain transcripts of some
      (CD3 gamma, TCR C beta, TCR C gamma 1, TCR C gamma 4) but not of other (CD3
      delta, CD3 epsilon, TCR C alpha, TCR C delta) genes encoding the CD3/TCR complex
      suggests that Thy-1+/CD3- fetal murine skin cells are of T cell lineage. We
      therefore propose that the fetal skin microenvironment can provide the stimuli
      promoting growth and maturation of CD3/TCR V gamma 3/V delta 1-expressing DETC
      from their CD3- precursors.

PMID- 1354680
TI  - Impaired calcium mobilization in CD4+ and CD8+ T cells in a retrovirus-induced
      immunodeficiency syndrome, murine AIDS.
AB  - After infection with LP-BM5 murine leukemia viruses, susceptible strains of mice
      develop a severe and progressive immunodeficiency disease, termed murine AIDS
      (MAIDS), features of which include markedly impaired T cell response to mitogens
      or specific Ag stimulation and decreased production of IL-2. Since an elevation
      of intracellular calcium concentration resulting from binding of Ag to the TCR is
      associated with IL-2 production, T cells from mice either uninfected or infected
      with LP-BM5 murine leukemia viruses were examined by a calcium mobilization
      assay. Both CD4+ and CD8+ T cells from infected mice manifested impaired calcium
      mobilization responses upon in vitro stimulation with anti-CD3 mAb or Con A. The
      abnormalities appeared early after virus inoculation and showed no difference in
      time course between subsets of T cells. Frequencies of prestimulation calcium
      positive cells among both CD4+ and CD8+ cells in mice with MAIDS were
      significantly higher than those for uninfected mice. These abnormalities were
      associated with presence of the MAIDS-inducing defective virus genome, but were
      not induced by infection of mice genetically resistant to development of MAIDS or
      with nonpathogenic helper murine leukemia virus, a virus component that induces
      high spontaneous proliferation of T cells, even in MAIDS-resistant mice.

PMID- 1354681
TI  - Effects of CD4 synthetic peptides on HIV type I envelope glycoprotein function.
AB  - Benzylated derivatives of a peptide (CD4(81-92)) representing the CDR3-like
      region of CD4 were previously found to inhibit gp120 binding, HIV-1 infectivity,
      and syncytium formation. These results have been interpreted to indicate a role
      for the corresponding CD4 region in these processes. The peptide
      (TbYICbEbVEDQKAcEE) is the prototype of a series of similar CD4(81-92)
      derivatives. We report that this peptide noncompetitively inhibits binding to CD4
      of both gp120 and a mAb (MAX.16H5), both of which recognize the CDR2-like region
      of CD4. The binding of an antibody (Leu 3a) that is directed against a different
      area of the D1 domain of CD4 was also inhibited. The peptide derivative inhibited
      both HIV-1- and HTLV-1-mediated syncytium formation in the same concentration
      range. Nonbenzylated cyclic and linear peptides representing the CDR3-like region
      of CD4 (CD4(84-101)) had only minor effects on gp120 binding which were not
      sequence specific. The results of this study suggest that the effects of
      benzylated CD4(81-92) derivatives on HIV-1 binding or fusion should not be used
      to reach conclusions about the function of the corresponding CD4 region.

PMID- 1354682
TI  - [A surgical case of thoracic aortic aneurysm due to Takayasu's aortitis
      associated with ulcerative colitis].
AB  - We experienced a case of thoracic aortic aneurysm due to Takayasu's aortitis
      associated with ulcerative colitis. Steroid was medicated to control inflammation
      and operation was performed. The ascending aorta, aortic arch, brachiocephalic
      artery, and left carotid artery were replaced by artificial graft. We made
      elephant trunk type anastomosis at the distal side of the graft to provide for
      growth of the aneurysm after operation. This was a rare case considered
      autoimmune overlapping syndrome, and its background was complicated by HLA-Bw52
      and parasitic Metagonimus Yokogawai. Relationship between steroid medication and
      progression of the disease is not certain yet. Postoperative course is
      uneventful, no recurrence of inflammation is seen and the aneurysm is not
      enlarged until now.

PMID- 1354683
TI  - Detection of bcr/c-abl mRNA in chronic myelogenous leukemia by polymerase chain
      reaction to identify chromosome translocation.
AB  - The hallmark of chronic myelogenous leukemia (CML) is the Philadelphia chromosome
      (Ph1) which is caused by a translocation of the c-abl gene from chromosome 9 to
      the breakpoint cluster region (bcr) on chromosome 22. Polymerase chain reaction
      (PCR) can be used to detect the chimeric bcr/c-abl mRNA as evidence of the
      translocation. We applied a very simple and quick method of isolating cytoplasmic
      RNA, as well as reverse transcription and PCR in detecting bcr/c-abl mRNA of
      seven CML patients in various stages. Our results showed that only a small amount
      of either peripheral blood or bone marrow material was required for the
      expression of the bcr/c-abl mRNA. This is a very fast and time-saving method
      since a one-step method of cytoplasmic RNA isolation is used instead of the
      several steps in total RNA isolation as published in other literature.

PMID- 1354684
TI  - Investigation into allergic response in patients with chronic sinusitis.
AB  - We attempted to investigate the role of nasal allergy in sinusitis to elucidate
      whether it results from an immediate-type allergic reaction of the sinus mucosa
      or from allergic edema-induced sinus ostial obstruction. Forty-two patients with
      chronic sinusitis were selected for allergen skin tests, measurements of serum
      total and specific IgE, and sinus tissue-specific IgE. The data were then
      correlated to examinations of nasal mucosal scrapings and histopathology of the
      sinus mucosa. We found that serum levels of total IgE and house dust mite
      specific IgE antibodies were significantly higher in patients (n = 12) allergic
      to house dust than in the nonatopics (n = 30; p less than 0.0001). There was no
      difference in the sinus tissue-specific IgE antibody. Eosinophils and basophilic
      cells in epithelial scrapings from the inferior turbinates, assessed by Hansel
      staining, were high in 66.7% and 50% of the atopic patients, respectively, and
      36.7% and 26.7% of the nonatopics, respectively. The rates were influenced by the
      existence of infection and nasal polyps. The increase in eosinophils, mast cells
      and plasma cells, assessed by histopathologic examination, were not prevalent in
      the sinus mucosa of atopic patients. It is concluded that nasal allergy may be a
      predisposing factor to sinusitis and that the pathologic change of the sinus
      mucosa is mainly secondary, due to sinus ostial obstruction.

PMID- 1354685
TI  - Changes in activity of cytochrome oxidase in the cochleae of guinea pigs with
      experimental endolymphatic hydrops.
AB  - Cochlear dysfunction may indicate inadequate generation of intracellular
      metabolic energy which is necessary for the regulation of the transport of ions
      and fluid as well as production of electro-energy in the cochlea. Changes in
      cochlear function in the early stages of endolymphatic hydrops attributed to
      dysfunction of the sensory hair cells and stria vascularis were investigated. The
      main source of metabolic energy, produced by intracellular respiration, is
      located in the stria vascularis and sensory hair cells. Since cytochrome oxidase
      is one of the most important respiratory enzymes, vibratome sections of hydropic
      and normal cochleae were stained cytochemically for cytochrome oxidase activity
      in this study. Decreased activity of this enzyme was consistently shown in the
      normal-appearing outer hair cells and stria vascularis, as well as the
      degenerated hair cells and stria vascularis, of the higher turns of the hydropic
      cochlea. The results coincide with those in other studies of electrophysiologic
      changes in cochlear function in hydropic animals. A decrease in the activity of
      respiratory enzymes was noted before the destruction of the cellular structures.
      The activity of cytochrome oxidase may serve as a useful indicator for
      demonstrating the functional status of cochlear hair cells and stria vascularis.

PMID- 1354687
TI  - Effect of tocopherol on platelet aggregation in non-insulin-dependent diabetes
      mellitus: ex vivo and in vitro studies.
AB  - Tocopherol has been shown to have antiplatelet effects in insulin-dependent
      diabetes mellitus. However, its antiplatelet effect in non-insulin-dependent
      diabetes mellitus (NIDDM) remains to be established. In this report, the
      antiplatelet effect of tocopherol was assessed in a randomized, double-blind and
      crossover study of 15 NIDDM subjects. Each subject received tocopherol (dl-alpha
      tocopherol nicotinate, 200 mg, tid) and a placebo for two six-week treatment
      periods separated by a three-week period in between for wash-out. The mechanisms
      of the antiplatelet effect of tocopherol were also studied in vitro. A
      significant decrease in platelet reactivity was observed after tocopherol
      treatment as compared with the pretest, and the magnitude of the decrease during
      tocopherol treatment was significantly evident when compared with that of the
      placebo treatment, as assessed by collagen (5, 10 micrograms/mL)-induced platelet
      aggregation of whole blood. A dose-dependent reduction in both ADP-and collagen
      induced platelet aggregation was observed with tocopherol from 0.1 to 3.0 mM in
      vitro. No corresponding changes in ATP secretion and thromboxane synthesis were
      observed. Tocopherol also significantly inhibited fibrinogen-induced aggregation
      of elastase-treated platelets at a concentration of 0.1 mM. We demonstrated that
      platelet aggregation of whole blood ex vivo, among 15 NIDDM subjects was
      suppressed in tocopherol treatment, so tocopherol may have an antiplatelet effect
      in NIDDM subjects. The inhibitory effect of the platelet aggregation of
      tocopherol may be partially accomplished through interference with fibrinogen
      binding towards its receptor.

PMID- 1354686
TI  - Diurnal variation of insulin sensitivity in NIDDM patients and normal subjects.
AB  - A modified insulin suppression test was adopted to assess the diurnal variation
      in insulin sensitivity and insulin clearance in 14 non-insulin-dependent diabetes
      mellitus (NIDDM) patients and eight age-, sex- and weight-matched normal
      subjects. The modified insulin suppression test was combined with an infusion of
      regular insulin, 30 mU/min x m2; glucose, 6 mg/kg x min; and somatostatin, 500
      micrograms/h, for 120 minutes followed by only a somatostatin infusion for 60
      minutes. Blood samplings were performed at appropriate times to obtain data on
      steady-state plasma insulin (SSPI), steady-state plasma glucose (SSPG as an index
      of insulin sensitivity), metabolic clearance and the half disappearance time
      (T1/2) of insulin. Blood specimens were also obtained during SSPI for measurement
      of erythrocyte insulin receptor binding. Each subject took the insulin
      suppression test twice. One test was started at 8 am and the other at 4 pm; each
      test was preceded by 16 hours of fasting. The order of the insulin suppression
      tests in each subject was randomized and balanced. In normal subjects, the SSPG
      level was lower in the morning than in the afternoon (118.0 +/- 43.6 vs 150.3 +/-
      34.2 mg/dL, p less than 0.05). The NIDDM patients had a higher SSPG in the
      morning (217.7 +/- 51.4 vs 188.3 +/- 40.6 mg/dL, p less than 0.01). There was no
      diurnal difference in insulin clearance or the T1/2 in either normal subjects or
      NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354688
TI  - Prenatal cytogenetic diagnosis in amniocentesis.
AB  - From 1982 to 1990, cytogenetic studies were successfully conducted in 2,975
      (96.19%) of the 3,096 pregnant women who underwent amniocentesis. The average
      maternal age was 33.7 years and the average gestational age was 18.1 weeks.
      Common indications of amniocentesis included advanced maternal age (AMA)
      (54.76%), previous fetus with chromosomal aberrations (6.82%) or gross anomalies
      (5.01%), intrauterine gross anomaly (4.97%) and maternal exposure to drugs or
      radiation (5.28%). Among the 89 cases (2.99%) with detected chromosomal
      aberrations, 53 were numeric (31 trisomies, 21 sex chromosome aberrations and one
      tripoidy) and 36 were structural (six de novo and 30 hereditary structural
      rearrangement). The incidence of chromosomal aberrations was 2.03% in cases with
      AMA. While only four of the 143 cases with previous fetal trisomy 21 had
      recurrence, the recurrent rate was 90.91% in 11 cases with previous fetal
      chromosomal translocation. Thirty (20.27%) of the 148 cases with abnormal
      sonograms showed chromosomal aberrations. Certain congenital anomalies are
      closely associated with cytogenetic changes: duodenal atresia and trisomy 21;
      cystic hygroma and 45,X; and polyhydramnios and trisomy 18. Only two of the 157
      cases with indications of drug or radiation exposure had abnormal cytogenetic
      studies. Two of the 53 cases with detected numerical aberrations (47,XXY and
      47,XXX) and 27 cases with hereditary structural rearrangement elected to continue
      their pregnancies. All of these babies were delivered without gross anomalies.
      This study suggests that for prenatal diagnosis. However, complementary measures,
      such as routine antenatal ultrasound and maternal serum alphafetoprotein, should
      be added to increase the efficacy of genetic amniocentesis.

PMID- 1354689
TI  - Serum gastrin levels in children with peptic ulcer disease.
AB  - Fasting serum gastrin values were measured by radioimmunoassay in 53 children
      with peptic ulcer disease. The mean fasting serum gastrin levels for children
      with chronic duodenal ulcer, acute gastric ulcer, acute duodenal ulcer who were
      younger than two years old and acute duodenal ulcer who were older than two years
      old were: 46.2 +/- 25.7 pg/mL, 46.9 +/- 43.5 pg/mL, 47.9 +/- 12.0 pg/mL and 37.5
      +/- 17.8 pg/mL, respectively. Children with peptic ulcer disease did not have
      elevated fasting serum gastrin levels when compared with age-matched controls. We
      conclude that a fasting serum gastrin value cannot be used as a screening test
      for peptic ulcer disease in children, except for Zollinger-Ellison syndrome.

PMID- 1354690
TI  - Breast milk beta-glucuronidase in breast milk jaundice.
AB  - Breast milk jaundice (BMJ) is the most common etiology of prolonged unconjugated
      hyperbilirubinemia in a newborn infant. The pathogenesis of BMJ has been studied
      by many investigators, yet the etiology still remains uncertain. A prospective
      study was done to examine the role of breast milk beta-glucuronidase in BMJ in
      healthy full-term Chinese newborns. There were 71 infants in the formula-fed
      group (FF group), 28 in the breast-fed group (BF group) and 27 in the mixed
      feeding group (MF group). Study infants were followed at the well-baby clinic for
      at least two months. Enzyme activity in maternal breast milk and infants' stools
      decreased significantly during the first week postpartum. There was no intergroup
      difference in fecal enzyme activity for the different age groups. Significantly
      more infants in the BF group (35.7%) developed prolonged unconjugated
      hyperbilirubinemia than did infants in the FF group (2.8%) and the MF group (0%).
      We did not find higher enzyme activity in breast milk or stools of infants with
      BMJ than in infants without BMJ. We, therefore, conclude that breast milk beta
      glucuronidase is not related to the development of BMJ.

PMID- 1354691
TI  - Comparison of different ligature materials used for T-tube esophageal exclusion.
AB  - Four different ligature materials--plain catgut, chromic catgut, dexon and silk-
      were used for ligature of the distal arm during T-tube exclusion of the cervical
      esophagus in 12 dogs. Ligature by plain catgut was maintained for only a short
      period, but the duration of esophageal occlusion with the other three ligature
      materials was around 10 days. Ligated esophageal segments were examined grossly
      and histologically two months after the procedure. The diameter of the esophageal
      lumen in the ligated segments had become smaller compared with the neighboring
      normal esophageal lumen. The most prominent histologic changes were atrophy and
      fibrosis of the muscle coat, vessel congestion and inflammatory cell infiltration
      in the ligated segments. These tissue reactions were more severe in the chromic
      catgut and silk ligatures. Among the 11 evaluable dogs, four had symptoms of
      dysphagia after removal of the T-tube. All four dogs had a sinus discharge and
      granuloma formation at the T-tube esophagostoma. The diameter of the esophageal
      lumen was more constricted in dogs with dysphagia. Among the four ligature
      materials, dexon had the advantages of a long duration of occlusion, less tissue
      fibrosis and little sequel of esophageal stenosis, making it the most suitable
      for ligature during esophageal exclusion.

PMID- 1354692
TI  - Meningeal carcinomatosis from solid tumors: clinical analysis of 42 cases.
AB  - From January 1984 to June 1990, we observed 42 patients with meningeal
      carcinomatosis, 20 men and 22 women, aged 21 to 80 years (median age, 53 years).
      The two most common primary malignancies were lung cancer (50%) and breast cancer
      (31%). Sixty-four per cent was adenocarcinoma. On the first lumbar puncture, 86%
      had malignant cells in the cerebrospinal fluid. The findings of brain computed
      tomography were hydrocephalus (62%), contrast enhancement in the cerebral sulci
      or basal cisterns (31%), concomitant parenchymal metastases (15%) and normal scan
      (18%). In five out of seven cases, myelography showed irregular filling defects
      over the spinal cord or cauda equina. Treatment results were evaluated in 24
      patients. Eight received radiation therapy (RT) alone, and 16 had combined
      therapy with RT plus intrathecal methotrexate (IT MTX). Of the patients who
      received RT alone, only one patient with lung carcinoma was stabilized
      clinically. Of the cases receiving combined therapy, seven improved clinically.
      Six of these were patients with breast carcinoma who received IT MTX via Ommaya
      reservoir. The latter had a median survival of 23 weeks. The follow-up period of
      the entire group of patients ranged from one day to 50 weeks. The median survival
      was four weeks. Based on this study, combined therapy with RT and IT MTX is
      indicated for breast carcinoma with meningeal carcinomatosis, but the therapeutic
      effects are uncertain for lung carcinoma and other malignancies.

PMID- 1354693
TI  - Calcaneocuboid joint deformity in clubfoot.
AB  - In the management of congenital clubfoot, recent attention has been given to the
      deformity of the calcaneocuboid joint in addition to the changes in the
      talonavicular, talocalcaneal and ankle joints. Fifty-five patients with 86
      clubfeet operated on in the past six years were retrospectively studied.
      Radiographically, the calcaneocuboid subluxations were graded from I to IV by the
      Thoemtz classification. The grading has some correlation with the gross
      deformity, although there is no statistical data to confirm it. Postoperatively,
      those with grade I feet seemed to have satisfactory results with a posterior
      release only or with a posteromedial release. Grade II-III feet generally
      required extensive posteromedial and lateral release. Those who had a
      calcaneocuboid release and reduction obtained better correction than those who
      did not. We conclude that calcaneocuboid subluxation should be appraised
      preoperatively and reduced during surgery in order to achieve good results.

PMID- 1354694
TI  - Results of Senning operation for transposition of great arteries.
AB  - We report our results with 10 infants and children who underwent atrial repair
      using the Senning operation between 1985 and 1990. All cases had abdominal situs
      solitus, levocardia and atrio-ventricular concordance (D-bulboventricular loop).
      Nine patients had simple D-transposition of the great arteries without
      ventricular septal defects (VSD) or left ventricular outflow tract obstruction.
      The other patient had a double outlet right ventricle with subpulmonic VSD and
      pulmonary hypertension (PHT) and underwent a palliative Senning procedure. All
      patients had a balloon atrial septostomy (BAS) before surgery, except for one
      with Taussig-Bing syndrome. One patient had a Blalock-Hanlon operation after BAS.
      The age at the time of surgery ranged from two months to four years seven months
      (mean: 22 months) and weight ranged from 4.3-12 kg. There were two hospital
      mortalities including the patient with VSD and PHT. All of the patients had
      echocardiographic examinations and six of the eight survivors received cardiac
      recatheterization four to 19 months (mean: 7.4 months) postoperatively. No baffle
      leaks were noted in the survivors. Two patients had both mild tricuspid
      regurgitation and slightly decreased right ventricular contractility, and one
      patient had a pressure gradient of 6 mmHg between the superior vena cava and neo
      right atrium. The clinical follow-up interval was eight to 64 months (mean: 31.4
      months). All survivors showed a sinus rhythm on their latest electrocardiogram
      and were participating in normal daily activities without medication.

PMID- 1354695
TI  - Management of bony defects in open grade III fractures.
AB  - Early soft tissue reconstruction is recommended in treating open grade III
      fractures. Yet, there are still controversies regarding the way to handle bony
      defects when the soft tissue reconstruction is completed. This is a retrospective
      study to evaluate various methods of treating bony defects after soft tissue
      reconstruction in open fractures. From May 1985 to June 1988, we experienced 16
      cases of open grade III fractures of the extremities with bony defects which
      received either local treatment with flap transfers (five cases) or free flap
      transfers (11 cases). The bony defects ranged from 3 cm to 10 cm in length.
      Cancellous bone grafting was performed in nine cases, and two of them received
      internal fixation at the same time. Seven cases received vascularized bone grafts
      (six fibulas and one iliac bone). Our results showed that bone grafting, with
      either a conventional cancellous bone graft or a vascularized bone graft, is
      useful in treating bony defects after soft tissue reconstruction. Internal
      fixation of the fractures after removing an extraskeletal fixator has the
      disadvantages of soft tissue breakdown and of possible infection. Early
      posterolateral bone grafting was beneficial if a cancellous bone graft was used
      on the tibia. Double free tissue transfers were quite useful, and we did not lose
      any free tissue transfers in our series. Vascularized bone grafts should be
      considered in cases where the osseous gap is greater than 6 cm, or where the
      recipient bed is bad.

PMID- 1354696
TI  - Clinical efficacy of transluminal extraction coronary atherectomy.
AB  - Mechanical revascularization has revolutionized the treatment of coronary artery
      disease. The transluminal extraction-endarterectomy catheter (TEC) system was
      developed recently and permits the excision and extraction of atherosclerotic
      lesions of the coronary artery and the bypass graft. The system includes a motor
      driven flexible torque catheter with rotating conical shaped stainless steel
      blades distally. The proximal end of the TEC system consists of a mechanical
      housing which controls the vacuum, the rotating cutter (750 RPM) and the cutter
      excursion (4 cm). After safety testing of the TEC system in dogs and human
      peripheral arterial disease, percutaneous transluminal coronary atherectomies
      employing the TEC have been performed in 25 patients (six women, 19 men, mean
      age, 64 +/- 12 years) with the diameter of the stenosis greater than or equal to
      75% in one or more coronary arteries. Twenty-eight atherosclerotic lesions were
      treated in 26 native coronary arteries. The overall success rate (less than 50%
      residual stenosis in all lesions) was 92%. There was one instance of hematoma
      proximal to the excised target lesion, and one instance of atherectomized debris
      embolization. There were no instances of dissection, perforation, coronary spasms
      or death related to the procedure. The results indicate that the TEC system can
      be used safely and effectively to treat coronary artery disease with a high
      success rate.

PMID- 1354697
TI  - Lumbar lordosis: normal adults.
AB  - Lumbar curvatures in 149 normal adults from the general population were studied.
      There were 76 men and 73 women with an average age of 50 years. The mean values
      of lumbar lordotic angle (LLA), lumbosacral angle (LSA) and sacral inclination
      angle (SIA) were 33.2 +/- 12.1 degrees, 11.4 +/- 4.7 degrees and 26.4 +/- 10
      degrees, respectively. A high correlation was noted between LLA and SIA (r =
      0.883, p = 0.0001). LLA is an ideal parameter for the evaluation of lumbar
      lordosis. The normal value of LLA can be defined as 20-45 degrees with a range of
      1 SD. No significant differences were noted in these three angles between males
      and females in any age group (LLA, p = 0.647; LSA, p = 0.80; SLA, p = 0.189).
      Also, X-ray findings indicated there were no significant differences between
      these three angles in spondylotic spines and those spines with a normal
      appearance from X-ray finding. The average LLA increased with age. Significant
      lumbar lordotic angle differences were noted between those patients less than 35
      years of age and those greater than 60 years, as well as in the 35-60 age group
      and the greater than 60 age group (p = 0.0056).

PMID- 1354698
TI  - Locomotor strategies before independent walking: prospective study of 50 mentally
      retarded children.
AB  - To investigate the association between pre-walking locomotor strategies and
      psychomotor developments in children with mental retardation (MR), 50 children
      with non-specific MR were included in this study. There were 29 boys and 21
      girls, 96% of whom had moderate to severe MR. They were followed from 4-53 months
      to 25-99 months of age, and their follow-up periods ranged from 10 to 48 months
      (mean 30 months). According to the pre-walking locomotor strategies, these
      children were categorized into three groups: the crawling group (n = 34) who used
      crawling or creeping as their main locomotion pattern before independent walking;
      the shuffling group (n = 9) who used shuffling prior to independent walking; and
      the direct-walking group (n = 7) who did not have any other locomotor strategies
      except rolling. In almost all motor developmental milestones, children in the
      direct-walking group developed earlier than those in the crawling and shuffling
      groups. Children in the crawling group had more advanced developments than those
      in the shuffling group. The difference in the mean ratio developmental quotients
      of the Bayley Mental Scale among the three groups was not significant. The
      present study showed that crawling may not be a necessary prerequisite for early
      ambulation or better cognitive function in MR children.

PMID- 1354699
TI  - Pelvic actinomycosis with colo-ileo-vesical fistula formation: report of a case.
AB  - Pelvic actinomycosis with multiple fistular formation is rarely reported in the
      literature. We herein present a case of pelvic actinomycosis with sigmoid colo
      ileovesical fistulae in a 36-year-old intrauterine device (IUD) user. She was
      admitted to the hospital because of general malaise, weight loss and bilateral
      palpable adnexal masses. Sonography showed bilateral adnexal masses which
      contained many echolucent spots. A barium enema examination revealed sigmoid colo
      ileo-vesical fistulae. A computed tomographic scan showed bilateral cystic
      adnexal masses, bilateral hydronephrosis and hydroureter. Preoperatively, pelvic
      malignancy was suspected. An exploratory laparotomy was performed. Bilateral tubo
      ovarian abscesses with extensive adhesions were found. Pathologic examination of
      the operative specimen revealed pelvic actinomycosis. The patient was treated
      with penicillin for 14 weeks and had a stable clinical course.

PMID- 1354700
TI  - CT findings of pediatric thoracic actinomycosis: report of four cases.
AB  - Thoracic actinomycosis is an uncommon disease, which may mimic malignancy,
      lymphoma or tuberculosis of the chest. In the past three years, four cases of
      thoracic actinomycosis have been found in children at our hospital. Their
      computed tomography (CT) findings included pulmonary infiltrates, a chest wall
      mass, pleural and pericardial effusion, mediastinum involvement and rib changes.
      Although the final diagnosis of Actinomyces infection depends on a bacterial
      culture and pathology, CT can play an important role in establishing the
      diagnosis and evaluating the extent of the disease.

PMID- 1354701
TI  - Acute pseudo-obstruction of the colon following partial splenic artery
      embolization: report of a case.
AB  - This is a case of a 45-year-old woman suffering from liver cirrhosis with
      hypersplenism who received a partial splenic artery embolization with gelfoam
      pieces. Thrombocytopenia and leukopenia improved immediately after treatment.
      Marked abdominal distention, metallic bowel sounds and combined small and large
      bowel distension with air-fluid levels as shown on a plain abdominal X ray were
      noted on the fifth day after the embolization procedure. Laparotomy was
      performed. No mechanical obstruction was found during surgery. Acute pseudo
      obstruction of the colon (Ogilvie's syndrome) was diagnosed. This condition was
      considered to be a complication of the partial splenic artery embolization and
      has not hitherto been reported.

PMID- 1354702
TI  - Circumaortic left renal vein: report of a case.
AB  - Circumaortic left renal vein is an uncommon anomaly which has not been previously
      reported in Taiwan. We describe a case of circumaortic left renal vein in a 15
      year-old girl who presented with intermittent hematuria. Angiogram revealed
      double left renal veins in the form of a venous collar. Computed tomography
      depicted the preaortic and retroaortic left renal veins clearly. In a survey of
      hematuria, circumaortic renal vein should be taken into consideration in a
      differential diagnosis, and an appreciation of the specific radiologic findings
      can help to establish the diagnosis easily. In addition, preoperative recognition
      of this uncommon anomaly is of supreme importance in a retroperitoneal operation
      in order to avoid massive bleeding.

PMID- 1354703
TI  - Postnatal development of GABAergic neurons in the gerbil cochlear nucleus: pre
      embedding and post-embedding immunocytochemical staining.
AB  - The purpose of this investigation was to compare the results obtained when
      plastic-embedded sections and vibratome-sliced sections were used to localize
      gamma-aminobutyric acid immunoreactivity (GABA-IR) in the gerbil cochlear nucleus
      (CN) during postnatal development. GABA-IR was mainly located in the perikarya of
      the neurons of the gerbil CN. At two days old, GABA-IR was found in plastic
      sections. No discernible GABA-IR was found in the vibratome slices at three to
      four days. At eight days, anti-GABA labeled cells were randomly located in the
      superficial and deep layer of the dorsal cochlear nucleus (DCN) in the vibratome
      sections, whereas they were mainly accumulated in the vicinity of the granule
      layer between the junction of the DCN and posteroventral cochlear nucleus (PVCN)
      in the plastic sections. At 14 days, anti-GABA labeled cells were reduced in
      number in the superficial third of the DCN in the vibratome slices and reduced in
      number in the junction between the DCN and PVCN in the plastic sections. At that
      time, a striking change was the formation of lamellation of the anti-GABA labeled
      cells mainly located in the middle third (fusiform layer) of the DCN in the
      plastic sections. A similar pattern of lamellation was found in the vibratome
      slices at 17-18 days. At three, four, six and eight weeks, the anti-GABA labeled
      cells were mainly located in the ventral part of the DCN close to the choroidal
      plexuses and the ventral part of the PVCN in the plastic sections. At six to 15
      months old, distinct anti-GABA labeled cells were located in the fusiform layer
      of the DCN and scattered in the PVCN in the plastic sections. Another striking
      change at this age was that numerous vacuoles with a mesh-like network were
      present in the PVCN.

PMID- 1354704
TI  - Plasma renin activity, aldosterone level, serum and urinary electrolytes in
      normal pregnant women aged 35 and older.
AB  - Plasma renin activity (PRA), the plasma aldosterone (PA) level, and serum and
      urinary electrolytes were measured in 39 elderly pregnant women of greater than
      or equal to 35 (Group 1) and in 60 pregnant women less than 35 (Group 2) every
      four weeks from the 20th week of gestation to the fourth week postpartum. The PRA
      and PA levels increased in both groups. The PA levels increased after the 20th
      week and reached a peak at the 32nd week of gestation, while PRA decreased after
      the 20th week of gestation. This dissociation was observed in both groups. Daily
      urinary sodium excretion in Group 1 was higher than that of Group 2, while daily
      potassium excretion was not different between the two groups. Higher aldosterone
      secretion was observed after the 20th week of pregnancy in Group 1. It is
      concluded that pregnancy in older women is associated with higher sodium
      excretion and aldosterone secretion.

PMID- 1354705
TI  - Peripheral and intracardiac concentrations of atrial natriuretic peptide in
      patients with heart disease.
AB  - To study the relationship between the plasma concentration of the atrial
      natriuretic peptide (ANP) and heart function and to discern the secretion pathway
      of ANP, we determined the peripheral plasma concentration of ANP in 18 heart
      patients and the intracardiac concentration of ANP in six heart patients during
      cardiac catheterization. All plasma was extracted through a Sep-Pak C18 cartridge
      by acid alcohol. The concentration of ANP was determined by a sensitive and
      specific radioimmunoassay method. We found that the plasma ANP concentration
      (pg/mL) in heart patients (ranging from 12 to 139, mean = 36.1 +/- 28.9) was
      statistically higher than that in normal adults (ranging from 8 to 20, mean =
      12.4 +/- 3.3, n = 16; p less than 0.05). The ANP level in heart patients was
      inversely correlated with the left ventricular ejection fraction (r = -0.53, p
      less than 0.05) evaluated by radionuclide angiocardiography. The intracardiac
      level of ANP was 88 +/- 58 at the superior vena cava, 77 +/- 55 at the inferior
      vena cava, 124 +/- 68 at the right atrium, 98 +/- 64 at the right ventricle, 107
      +/- 58 at the pulmonary artery, 98 +/- 52 at the left ventricle, 109 +/- 73 at
      the aorta and greater than 351 at the coronary sinus. In conclusion, ANP is
      mainly secreted via the coronary sinus into the atrial cavity. The peripheral
      plasma ANP concentration is higher in heart patients. It increases as the left
      ventricular ejection fraction decreases. Therefore, plasma ANP concentration may
      be a useful indicator for the assessment of cardiac function.

PMID- 1354706
TI  - Metformin-induced lactic acidosis: report of a case.
AB  - Lactic acidosis associated with diabetic patients receiving metformin therapy is
      rare but may cause significant morbidity and mortality. In nearly all reported
      cases of metformin-associated lactic acidosis, contraindications to its use were
      noted, especially renal insufficiency. We describe a 59-year-old diabetic man
      treated with metformin for more than three years. During the third year of use,
      he experienced progressive renal function impairment, and during the final month
      of use, he became azotemic. He was maintained on continuous ambulatory peritoneal
      dialysis. Several days prior to admission, he suffered from epigastralgia, nausea
      and vomiting, followed by progressive dyspnea which was Kussmaul in nature.
      Profound hypotension developed and he sank progressively into a coma. Wide-anion
      gap metabolic acidosis without ketonemia was detected. His blood lactate level
      was elevated and metformin-induced lactic acidosis was substantiated. An elevated
      plasma metformin level of greater than 50 mg/mL was determined later by high
      performance chromatography. Rigorous treatment including bicarbonate therapy,
      bicarbonate hemodialysis and vasoactive agents as well as supportive measures
      were provided. With a return of pH to normal, the hypotension resolved and his
      consciousness level slowly improved. Our patient survived this disastrous event,
      but some neurologic sequelae remained. In order to avoid this life-threatening
      metabolic disturbance, patients with any contraindications should not be
      prescribed metformin.

PMID- 1354707
TI  - [Primary lung cancer in Taiwan].

PMID- 1354708
TI  - [Uterine cervical cancer in Taiwan].

PMID- 1354709
TI  - [Investigation of the profile of selected trace metals in genetically obese
      (ob/ob) and lean (+/?) mice].
AB  - Trace metals are known to have important effects on the activity of
      metalloenzymes and insulin secretion and to be involved in the etiology of
      various diseases. This study was designed to investigate the distribution and
      concentration of selected trace metals in the tissues of genetically obese mice,
      which were known to have hyperinsulinemia. Different phenotypes (ob/ob; +/?) and
      sexes of 4, 8, 12 week-old mice were killed by decapitation. Metal levels (Zn,
      Cu, Cd, Cr) in the brain, liver, serum, hair and carcass were determined by an
      atomic absorption spectrometer. The results showed that obese mice had lower
      concentrations of zinc in the serum, hair, liver and carcass than lean controls
      (p less than 0.05), but there was no difference in the brain. Obese mice also had
      a low carcass cadmium concentration (p less than 0.01), which depended on the sex
      age interaction. When expressed in terms of total content, obese mice had higher
      total liver zinc and carcass chromium contents (p less than 0.05). Obese mice had
      a higher total carcass copper content at 8 weeks of age. Serum and carcass zinc
      were showed to be inversely related to body fat in obese mice. The results
      indicate that zinc may play a special role in thermoregulation and fat metabolism
      in the liver of obese mice. The tissue distribution and absorption of zinc may
      have an important correlation in the development of obesity. The roles of copper,
      cadmium and chromium are still obscure, the related regulations are still open
      for further questions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354710
TI  - [An animal model for colon cancer metastases to the lung and establishment of
      metastatic cancer cell line].
AB  - Death, in most colon cancer patients, is not caused by their primary tumors.
      Instead, metastasis is the major cause of morbidity and death. There are few
      appropriate animal models to investigate the complexity of the metastatic
      process. Therefore, the pathogenesis of the metastasis process is not clearly
      understood. We injected SW480 cells into the cecal wall of athymic nude mice to
      develop an animal model for colon cancer metastasis and to produce a
      metastasizing tumor. After metastatic foci formed in the murine lung, we
      established a metastatic cancer cell line, named CC-ML1, by in vitro primary
      culture. The characteristics of CC-ML1 were (1) a shorter doubling time; (2) a
      slightly higher metastatic rate and number of colonies; and (3) less
      morphological variation than those of SW480. Our research suggests that a higher
      metastatic potential may be found in CC-ML1 than in SW480 after the advanced
      cycles of the metastatic process. Thus, the primary animal model in this study
      may be useful in future studies of cells with a high metastatic potential in the
      pathogenesis of colon cancer metastases.

PMID- 1354711
TI  - [A study of perigastric lymph node metastasis in patients with early gastric
      cancer].
AB  - The prognosis after a gastrectomy for early gastric cancer (EGC) is favorable.
      Among 115 patients with early gastric cancer since 1983, 96 patients have
      received a radical gastrecomy (RG) and 19 have received a simple gastrectomy
      (SG). The cancer was confined to the mucosa in 47 cases and had invaded into the
      submucosa in 68 cases. Perigastric lymph nodes metastasis was observed in 17
      patients (14.8%). The metastatic rate for mucosal cancer was 2.1% and that of
      submucosal cancer was 23.5% (p less than 0.005). Advanced nodal metastasis was
      occasionally visible in a few patients with submucosal cancer. The macroscopic
      pattern, size, primary site and differentiation of the cancer and the age and sex
      of the patients did not influence the rate of nodal metastasis. A follow-up study
      of 61 patients with EGC operated on before 1988 was carried out, the 5-year
      survival rate of RG was 92.9% and that of SG was 84.2% (p = 0.3109). The 5-year
      survival rate for mucosal cancer for RG was 100% and that for was 90.9% (p =
      0.3048). The 5-year survival rate for submucosa] cancer for RG was 89.3% and that
      for SG was 75.0% (p = 0.0685). We suggest that RG be mandatory for EGC unless the
      depth of invasion is confined to the mucosa in the preoperative diagnosis, or if
      gross advanced metastasis is present to obtain more accurate postoperative
      staging and to achieve a curative resection. However, SG is still an alternative
      treatment for EGC if a patient's condition is poor or for extremely old patients.

PMID- 1354712
TI  - [Intraoperative pleural lavage in lung cancer patients].
AB  - In lung cancer patients, pleural effusion may or may not be present even if
      cancer cells have invaded the pleura. Using the traditional staging methods, not
      all pleural metastasis can be detected before the presence of pleural effusion.
      We performed intraoperative pleural lavage on 38 patients who underwent a
      thoracotomy due to tumors of the lungs. The first lavage (lavage 1) was performed
      just after the pleural cavity was open; the second lavage (lavage 2) was
      performed after all surgical procedures were completed (including lung resection
      and mediastinal lymph node dissection). Totally 12 of the 32 primary lung cancer
      patients were found to have positive lavage 1 cytology; 13 had positive lavage 2
      cytology. In 13 patients whose visceral pleura was invaded by tumor, 11 had a
      positive lavage 1, 10 had a positive lavage 2. For prediction of positive lavage
      1 cytology from visceral pleural involvement, the accuracy was 90.6%, the
      sensitivity was 84.6%, the specificity was 94.7%, the positive predictive rate
      was 91.7%, the negative predictive rate was 90.0%. For lavage 2, the accuracy was
      81.2%, the sensitivity was 76.9%, the specificity was 84.2%, the positive
      predictive rate was 76.9%, the negative predictive rate was 84.2%. Stage of
      disease and cell type seemed to have no relationship to the incidence of positive
      lavage fluid cytology. Further investigation is recommended to evaluate the
      prognosis of patients with positive lavage fluid cytology.

PMID- 1354713
TI  - [Secular trends in mortality for cerebrovascular diseases in Taiwan (1959-1989)].
AB  - Cerebrovascular disease (CVD) is predominantly a disease of the elderly, and its
      morbidity effects increase with advancing age. In Taiwan, the increasing
      proportion of the elderly, as a result of medical progress and improved health
      care in the past 30 years, is largely responsible for the apparent increase in
      the number of CVD deaths. From 1963 to 1981, CVD was the leading cause of death.
      The crude mortality rate (CMR) and age-specific mortality rate (ASMR) of CVD by
      sex were derived from vital statistical data from 1959 to 1989 in Taiwan. The age
      adjusted mortality rate (AAMR) using the standard world population of WHO and the
      cumulative mortality rate (CUMR) from birth to less than 80 years of age were
      calculated. Before 1983, the total number of CVD deaths had increased steadily
      for 30 years. In 1989, the CMR was 76.6/100,000 in men and 67.7/100,000 in women.
      The highest AAMR was 158.5/100,000 in 1973 for men and 130.2/100,000 in 1972 for
      women, and the lowest AAMR was 91.3/100,000 in 1989 for men and 81.1/100,000 in
      1972 for women. The highest CUMR was 26.3% in 1968 for men and 20.8% in 1972 for
      women, and the lowest CUMR was 14.5% in 1989 for men and 13.6% in 1989 for women.
      The AAMR and CUMR for both sexes reached a maximum in 1972 and began to decline
      thereafter. The declines in AAMR and CUMR were averaging 2%/yr for both sexes
      after 1972 and were averaging 5%/yr for men and 4%/yr for women after 1983. This
      declining trend in CVD deaths in Taiwan began later and has been slower than
      similar trends in Japan and the U.S.

PMID- 1354714
TI  - [Effects of PGE1 on penile blood flow].
AB  - From February to July in 1989, 47 patients came to our O.P.D. with the chief
      complaint of impotence. The average age was 48.3 +/- 10.7 y/o. We applied
      intracoporeal injection of prostaglandin PGE1 (20 mg); and evaluated its penile
      blood flow effect by color duplex scanning (Acuson 128). The erectile responses
      of the test showed that: 6 patients (12.8%) had normal response: and 16 patients
      (34%) had imperfect response. Altogether, the total positive response rate was
      46.8%, and 25 patients (53.2%) showed impaired response. The onset of response
      was 9.1 +/- 3.6 minutes and the duration of erection was 59.2 +/- 24.7 minutes.
      The percentage of diameter change of both deep arteries after injection was Rt:
      58.1 +/- 41.5%; left: 52.3 +/- 35.6%. The peak velocity of right cavernosal
      arterial flow after intracoporeal injection was 35.5 +/- 15.9 cm/sec; and that of
      the left side was 33.2 +/- 16.9 cm/sec. There was no correlation between the
      increment of peak velocity of the deep arterial flow and the erection grade. The
      same phenomenon was also found between the increased change in the diameter of
      the deep artery and the erection grade. 16 patients (34.1%) experienced tolerable
      pain during the procedure. Two patients (4.3%) experienced dizzines and
      discomfort due to venous leakage. No priapism was found. This study suggests PGE1
      may be an excellent potential alternative to other vasoactive drug with less
      complication in the diagnosis and treatment of impotence. But the cost and
      stability were its shortcoming.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354715
TI  - [Thyroid function tests in acute drug intoxication].
AB  - It is well known that thyroid function tests may be changed in non-thyroidal
      illnesses. To understand the influence of acute drug intoxication on thyroid
      function tests, 31 drug intoxicated patients without previous thyroid disorders
      and systemic diseases were included in our study. T3, T4, TSH, and resin T3
      uptake were checked as soon as they arrived at our emergency service and were
      compared to that of 58 healthy volunteers. Within 31 patients, 14 were
      intoxicated by organophosphorous compounds, 6 by sedatives and hypnotics, 3 by
      strong acid, 2 by paraquet, 2 by rodenticides (warfarin), 2 by lysol and the
      other 2 were intoxicated by acetaminophen. The mean T3 and TSH levels were
      significantly lower in the drug intoxicated group. Among the 31 patients, 14
      (45.2%) had a low T3, 2 (6.5%) had a low T3 and T4, and 6 (19.3%) had an elevated
      T4. All of the patients with an elevated T4 were intoxicated by organophosphates.
      If we divided the 31 patients into 2 subgroups: organophosphate intoxicated group
      and non-organophosphate intoxicated group, T4 and FT4I were significantly higher
      in the former group. Thyroid function tests became normal after treatment in 27
      patients, discharged in good general condition. T3 and T4 became extremely low in
      4 patients before they expired. The present study confirms that acute drug
      intoxication, like other non-thyroidal illnesses, affects thyroid function tests.
      Acute organophosphate intoxication may cause transient hyperthyroxinemia.

PMID- 1354716
TI  - [Uterine lipoleiomyoma with calcification: report of a case].
AB  - Uterine lipoleiomyoma is uncommon and has received little attention from
      gynecologists. We report a case of uterine lipoleiomyoma with subsequent pelvic
      abscess after rupture of the appendix. Its clinical picture mimicked uterine
      malignancy. The patient was a 60-year-old woman, who presented with a 2-week
      period of lower abdominal pain which was exacerbated 10 days later. After
      admission, gynecologic examination revealed a large pelvic mass of firm
      consistency. On a plain film of the abdomen, there was a large calcified mass in
      the pelvis. Pelvic ultrasound demonstrated a 15 yen 12 yen 12 cm mass with strong
      echogenicity in the margin, but the central component of the mass was attenuating
      and revealed a poorly defined echogenic mass. A computed tomography scan of the
      pelvis demonstrated a well-encapsulated mass that was predominantly the density
      of fat (-65 Hounsfield unit) in the central part, with calcification present in
      the peripheral layer of the mass. There was also a cystic lesion measuring 3 yen
      2.5 yen 1.5 cm in the right adnexal area. A preoperative diagnosis of uterine
      lipoleiomyoma with necrosis, liposarcoma of the uterus or teratocarcinoma of the
      ovary was made by the CT scan. A diagnostic dilatation and curettage (D&C)
      revealed a uterine cavity length of 12 cm by sounding, and the specimen showed no
      malignant tissue. Therefore, the preoperative suspicion of ovarian
      teratocarcinoma could be excluded. The patient underwent an exploratory
      laparotomy, multiple pockets of pelvic abscess, enlargement of the uterus and
      induration of omentum surrounding the appendix were found.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1354717
TI  - [Chronic chromate intoxication with renal tubular damage--report of a case].
AB  - A 46-year-old male chromium plating worker visited our hospital due to
      rhinorrhea, sneezing and cough with blood-tinged sputum for more than 10 years.
      He also had skin ulceration and chronic dermatitis on both hands Medical therapy
      was inefficient. Physical examinations revealed nasal septum perforation, severe
      inflammation of the nasopharynx cavity, and eczema of both hands. Laboratory
      investigations showed significant tubule proteinuria, enzymuria, hypercalciuria,
      etc. It is evident that renal tube damage was present in this patient. The blood
      chromium level was 25 ng/mL, and the 24-hour urine chromium excretion level was
      2.8 mg/day. A pulmonary function test showed reduced functional residual capacity
      (FRC), which may be due to either long-term smoking or chromate acid exposure. To
      our knowledge this is the first case of renal tubal damage induced by chronic
      chromate intoxication Taiwan. Further evaluation of the occupational safety and
      health of chromium plating workers is needed on this island.

PMID- 1354718
TI  - [Nasopharyngeal carcinoma in Taiwan].

PMID- 1354719
TI  - Ubiquitin-reactive axons have a widespread distribution and are unrelated to
      prion protein plaques in Creutzfeldt-Jakob disease.
AB  - The amyloid plaques of Alzheimer disease (AD) are surrounded by dystrophic axons
      that contain ubiquitinated dense bodies. To investigate whether deposits of other
      types of amyloid cause axonal degeneration we studied 5 cases of Creutzfeldt
      Jakob disease (CJD) with immunocytochemical methods using ubiquitin and prion
      protein (PrP) antisera. One of these cases contained PrP plaques in the
      cerebellum. In all cases dystrophic axons, which contain ubiquitinated dense
      bodies, were observed in neocortical and cerebellar grey matter, in absence of
      PrP-reactive amyloid deposits. Only a minority of PrP plaques present in the
      cerebellum was associated with ubiquitin positive neurites. The results indicate
      that, unlike in AD, the occurrence of ubiquitinated dystrophic axons is
      independent from amyloid deposition in CJD and is likely to be a primary
      phenomenon.

PMID- 1354720
TI  - Dissociated neurons of the pupal honeybee brain in cell culture.
AB  - Primary cell cultures were prepared from specific regions of the pupal honeybee
      brain which are involved in proboscis extension learning. Defined areas could be
      dissociated purely by mechanical treatment. We show that cultured neurons
      regenerate new neurites and remain viable for up to three weeks in a serum-free,
      chemically-defined medium. Several labelling techniques were employed to identify
      subpopulations of cultured neurons. For example, acetylcholinesterase staining;
      fluorescent beads to distinguish identified cell populations of co-cultured brain
      areas; various markers for surface antigens such as a monoclonal antibody to
      olfactory projection neurons of the antennoglomerular tracts and monopolar cells
      of the optic lobes, as well as anti-HRP immunoreactivity and alpha-bungarotoxin
      binding; and various antisera for detecting transmitter phenotype. The appearance
      of transmitter-immunoreactive cells agreed closely with that expected from their
      known distribution in situ. Our results suggest that cultured cells retain
      surface properties and transmitter phenotype of their in vivo counterparts,
      despite differences in basic morphology. Thus our culture system provides the
      important initial step for future in vitro investigations of the cellular and
      electrophysiological properties of neurons mediating proboscis extension
      learning.

PMID- 1354721
TI  - The effect of 5-lipoxygenase inhibition on blood-brain barrier permeability in
      experimental brain tumors.
AB  - To determine if leukotrienes are important mediators of vascular permeability in
      brain tumors, the effect of 5-lipoxygenase inhibitors on blood-tumor barrier
      permeability in rats harboring HK Walker 256 brain tumors was examined using
      quantitative autoradiography with alpha-14C-aminoisobutyric acid. The 5
      lipoxygenase enzyme converts arachidonic acid to leukotrienes. Three 5
      lipoxygenase inhibitors were utilized: BW755C, nordihydroguaiaretic acid, and AA
      861. All three 5-lipoxygenase inhibitors significantly decreased vascular
      permeability both within the tumors and in brain adjacent to tumor. This suggests
      that capillary permeability in and adjacent to tumors is influenced by endogenous
      leukotrienes and that leukotrienes play an important role in brain tumor edema.

PMID- 1354722
TI  - Oral benzodiazepines and conscious sedation: a review.
AB  - A large number of benzodiazepines have been studied for use as sedatives and for
      their anxiolytic potential as premedicants for outpatient surgery. Potent, new,
      orally-administered drugs with short half-lives, rapid onset, and minimal
      residual effects have been developed. Dose-dependent amnesia is also produced by
      some of these agents. Advances in understanding receptor physiology have shed
      light on specific pharmacologic activities and aided the discovery of
      benzodiazepine antagonists with antidote properties. While these drugs have
      relatively low toxicity, dose-related oversedation remains a risk in susceptible
      patients, especially when combined with other sedatives.

PMID- 1354723
TI  - Delayed hypersensitivity skin tests in prognosis of human immunodeficiency virus
      infection.
AB  - Delayed hypersensitivity skin tests (DHST) with recall antigens were investigated
      as prognostic markers in five different approaches. In the first study, 42
      acquired immunodeficiency syndrome (AIDS) patients (IVb, IVcl, IVd, and IVe; MMWR
      35:334-339, 1986) 26 AIDS-related complex (ARC) patients (IVa and IVc2), and 98
      asymptomatic patients (II and III) were evaluated with candidin, tricophytin, PPD
      and streptokinase-streptodornase. In the second study, 10 patients (II and III)
      were evaluated sequentially with the same antigens. In the third, 45 patients
      with at least two positive skin tests ("reactors") were followed for one year and
      evaluated every 6 months with the same antigens. In the fourth, 16 "reactors"
      were followed and evaluated every 3 months with the same antigens. We measured
      the interval from the time at which patients first presented with only one or no
      positive DHST until the development of ARC or AIDS. In the last study, the
      correlation between absolute number of CD4+ lymphocytes and the number of DHST
      was studied in 151 patients. We found that the decrease in reactiveness to DHST
      correlated directly with the progression to AIDS, demonstrating the usefulness of
      this simple procedure as a valid prognostic marker.

PMID- 1354724
TI  - Conference on equivalency and superiority claims for products for gingivitis and
      periodontitis. Chicago, Illinois, May 14-16, 1991.

PMID- 1354725
TI  - Evaluation of ion-exchange microspheres as carriers for the anticancer drug
      doxorubicin: in-vitro studies.
AB  - A comparison study of doxorubicin loading, release characteristics and stability
      within sodium and hydrogen forms of ion-exchange resin microspheres has been
      performed. It was demonstrated that resins in the Na+ form, although having lower
      drug loading capacity, showed similar release profiles to resins in the H+ form
      but still maintain all the drug activity. Resins in the H+ form, despite having
      high drug loading capacity, caused drug degradation within microspheres due to
      their strong acidic nature. Therefore, in comparison with the H+ form, resins in
      the Na+ form can be considered as better carriers for doxorubicin in terms of
      sustaining the release of drug and maintaining drug activity. Other factors such
      as the degree of resin cross-linkage and drug/resin mixing time have also been
      examined in relation to drug loading and release characteristics. Overall, this
      study demonstrated the significance of the characteristics of matrix materials
      and their influence on the drug activity and microsphere performance in-vitro.

PMID- 1354726
TI  - Effects of proteolytic enzyme inhibitors as absorption enhancers on the
      transdermal iontophoretic delivery of calcitonin in rats.
AB  - The effects of proteolytic enzyme inhibitors, aprotinin, soybean trypsin
      inhibitor and camostat mesilate as absorption enhancers on the transdermal
      iontophoretic delivery of salmon calcitonin (SCT) have been examined in rats. The
      dermal absorption of SCT was evaluated with hypocalcaemic effect. Application of
      SCT (12.5 int. units/rat) onto abdominal skin did not produce any hypocalcaemic
      effect. This produced a small hypocalcaemic effect with cationic iontophoresis
      (drug phase, anode; reference phase, cathode; high frequency pulses of 1 V at 10
      kHz, 2h). Furthermore, camostat mesilate (1 mM) and aprotinin (10(6) int. units
      mL-1) enhanced the hypocalcaemic effects on the application of SCT with
      iontophoresis. These hypocalcaemic effects were highest with the pH 4.0
      preparation compared with those of the pH 5.5, pH 7.0 and pH 8.0 preparations.
      However, soybean trypsin inhibitor did not change the hypocalcaemic effects. This
      was because the soybean trypsin inhibitor is a relatively high molecular weight
      peptide (mol. wt 8000) and an anion at used pH, and therefore was not absorbed
      through rat skins with cation iontophoresis.

PMID- 1354727
TI  - Effect of a perfluorochemical emulsion on the rat hepatic mixed function oxidase
      system.
AB  - The perfluorochemical components of synthetic oxygen transporting emulsions may
      persist in hepatic tissue. After a single 30% blood exchange with the
      perfluorochemical emulsion, Fluosol-DA 20%, the effects on the microsomal
      metabolism of 7-methoxycoumarin and 7-ethoxycoumarin were studied over a 9-week
      period. Fluosol-DA treated animals were compared with controls (sham) and
      hetastarch-treated controls. Changes in dealkylase activities were compared with
      induction by phenobarbitone and 3-methylcholanthrene. The liver to body weight
      ratio increased by 49% in Fluosol-DA-treated rats over the controls at 1 week and
      the microsomal protein was increased in the Fluosol-DA-treated rats after 4 and 9
      weeks. Fluosol-DA treatment induced 7-methoxycoumarin demethylase with peak
      differences occurring at 1 week and a Vmax 75% greater than controls. Fluosol-DA
      was a more potent inducer of demethylase than phenobarbitone. In addition, 7
      ethoxycoumarin de-ethylase was induced by Fluosol-DA with a peak induction at 4
      weeks. The Vmax at 4 weeks in Fluosol-DA-treated rats was 122% greater than
      control. In this case, Fluosol-DA produced less induction in de-ethylase than 3
      methylcholanthrene. These studies show that Fluosol-DA induces more than one form
      of cytochrome P450 and the effects resemble those of phenobarbitone more than
      those of 3-methylcholanthrene. Hetastarch, a plasma expander, did not affect
      liver weights, microsomal protein content, or the cytochrome P450 system.

PMID- 1354729
TI  - Effect of calcium channel blockers on postprandial gastrointestinal motility in
      the dog.
AB  - We have compared the ability of nifedipine and lacidipine, a new 1,4
      dihydropyridine, to interfere with postprandial gastrointestinal motility. Five
      conscious dogs, fitted with 8 bipolar electrodes along the gastrointestinal
      tract, were studied. Gastrointestinal spike activity was evaluated by means of a
      computer system. Lacidipine (8 micrograms kg-1) was administered as an i.v. bolus
      immediately followed by a 10 micrograms kg-1 h-1 i.v. infusion for 3 h, starting
      30 min before a standard meal. This dose of lacidipine decreased systolic blood
      pressure by approximately 20%. Nifedipine was used at equihypotensive doses (30
      micrograms kg-1 i.v. bolus followed by 300 micrograms kg-1 h-1 i.v. infusion).
      Lacidipine had no effect on either gastric or intestinal postprandial spike
      activity. Nifedipine significantly delayed the appearance of the fed pattern and
      reduced the number of spikes in the small bowel, while it had no effect on
      gastric spike activity. We conclude that equihypotensive doses of lacidipine and
      nifedipine differ in their effects on the gastrointestinal tract, lacidipine
      having a better cardiovascular selectivity profile than nifedipine, and that the
      sensitivity to nifedipine varies in different parts of the gut.

PMID- 1354728
TI  - Time course of PAF formation by gastrointestinal tissue in rats after castor oil
      challenge.
AB  - When castor oil was administered by gavage to rats, the duodenum and jejunum, but
      not the stomach, produced large amounts of platelet activating factor 3-7 h after
      oil challenge with a peak at 3 h. Intraluminal release of acid phosphatase was
      also markedly increased in the duodenum and jejunum of castor oil-treated rats,
      especially 3-5 h after oil challenge. No increase was observed in the stomach.
      There was a correlation between elevated release of acid phosphatase and
      intestinal hyperaemia.

PMID- 1354731
TI  - Effect of cocaine on tritium overflow evoked from vasa deferentia previously
      loaded with [3H]noradrenaline by stimulation using different types of electrode.
AB  - In mouse and guinea-pig vasa deferentia previously incubated with
      [3H]noradrenaline, electrical stimulation applied through parallel electrodes
      (transmurally) increased overflow of tritium 2- to 5-fold above the resting
      value. Electrical stimulation applied using methods involving more substantial
      conduction of nerve impulses in neuronal elements in the tissues evoked a tritium
      overflow which was smaller (70%) than that evoked by transmural stimulation.
      Cinchocaine (25 microM), tetrodotoxin (0.5 microM) or the absence of calcium
      effectively abolished evoked overflow in both tissues whichever method of
      stimulation was used. In mouse vas deferens, cocaine (10 microM) did not alter
      overflow evoked by either transmural or axonal stimulation while 100 microM
      produced a reduction. In guinea-pig vas deferens, cocaine (10 microM) produced a
      statistically significant increase in evoked overflow of about 50% or more with
      both transmural and axonal stimulation. As in mouse vas deferens, 100 microM
      cocaine produced a reduction. It is concluded that the action of cocaine is
      independent of these methods of stimulation and that some difference in the
      arrangement of the noradrenergic nerves in the two species may account for the
      differential effect of cocaine observed.

PMID- 1354730
TI  - Different sites of action for alpha 2-adrenoceptor antagonists in the modulation
      of noradrenaline release and contraction response in the vas deferens of the rat.
AB  - Rat vas deferens was prepared, loaded with [3H]noradrenaline, and superfused to
      measure the release of tritium in resting conditions and in response to
      electrical field stimulation. The alpha 2-adrenoceptor antagonists yohimbine, CH
      38083 (7,8-(methylenedioxi)-14 alpha-hydroxyalloberbane HCl), and idazoxan
      increased the electrically induced release of tritium in a concentration
      dependent manner, whereas noradrenaline and the alpha 2-adrenoceptor agonist
      xylazine exerted opposite effects. The inhibitory effect of noradrenaline on
      electrically induced tritium release was antagonized by yohimbine, CH-38083, and
      idazoxan. Of the alpha 2-adrenoceptor antagonists tested, yohimbine and CH-38083
      reversed the xylazine-induced inhibition of tritium release, and idazoxan was
      found to be completely ineffective against xylazine. Idazoxan, yohimbine and CH
      38083 antagonized the inhibitory effect of xylazine on electrical stimulation
      induced contractions of the vas deferens, as was evidenced by the apparent pA2
      values. We conclude from the present experiments that noradrenaline and xylazine
      inhibit noradrenaline release by acting on distinct prejunctional alpha 2
      adrenoceptors and that the receptor subtype that responds to xylazine is
      insensitive to idazoxan. In addition, inhibition by xylazine of contractility but
      not of noradrenaline release was antagonized by idazoxan, suggesting that besides
      noradrenergic neurotransmission, other motor transmitter systems (purinergic) may
      also be involved in the inhibition by alpha 2-adrenoceptor antagonists of
      mechanical responses in the rat vas deferens.

PMID- 1354732
TI  - Effects of (+/-)-, (+)- and (-)-celiprolol on the rat left atria and portal vein.
AB  - Differing effects of (+/-)-celiprolol at beta-adrenoceptors have been reported.
      The effects of (+/-)-, (+)- and (-)-celiprolol on the contractile responses of
      the rat left atria and portal vein have therefore been studied. (+/-)-Celiprolol
      did not augment the responses of the atria to electrical stimulation and is
      therefore not an agonist at beta 1-adrenoceptors. Prolonged treatment with (+/-)
      celiprolol attenuated the contractile activity of the vein and this effect was
      blocked by ICI 118,551 and is therefore mediated by agonism at beta 2
      adrenoceptors. The pA2 values for (+/-)-, (+)- and (-)-celiprolol at the beta 1
      adrenoceptors of the atria were 8.0, 6.0 and 8.6, respectively. On the protal
      vein, (+/-)- and (-)-celiprolol produced non-parallel rightward shifts of log
      isoprenaline attenuation curves with a reduction in isoprenaline maximum
      responses. This effect of (+/-)-celiprolol on the vein was not due to slowly
      reversible antagonism, as the inhibitory effect of (+/-)-celiprolol was readily
      reversible.

PMID- 1354733
TI  - A possible mechanism of endothelium-dependent relaxation induced by pirarubicin
      and carbachol in rat isolated aorta.
AB  - The mechanism of endothelium-dependent relaxation induced by pirarubicin, (2''R)
      4'-O-tetrahydropyranyladriamycin, THP, or carbachol was investigated in the rat
      isolated aorta. The relaxant effect of THP (1.5 x 10(-6)-4.5 x 10(-5) M) or
      carbachol (10(-8)-10(-4) M) on the aorta with endothelium was decreased by
      lowering Ca2+ in the medium. The relaxation induced by THP was not inhibited by
      pretreatment with verapamil (10(-6)-10(-5) M), and that induced by carbachol was
      only partially inhibited. However, on replacement of all but 20 mM Na+ with
      either Li+ or choline, the THP- or carbachol-induced relaxation was inhibited.
      Furthermore, the relaxing effect of THP or carbachol was inhibited by
      pretreatment with amiloride (10(-4)-3 x 10(-4) M), with ouabain (10(-4)-10(-3)
      M), or with K(+)-depletion. These results suggest that the THP- or carbachol
      induced relaxation depending on endothelium was affected by modifying the calcium
      ion concentration, and that a Na(+)-Ca2+ exchange process is involved.

PMID- 1354735
TI  - Renal clearance-lipophilicity relationships of some organic acids in rabbits,
      rats and mice.
AB  - The effect of lipophilicity on the renal clearance for a group of weak organic
      acids (benzoic, phenylacetic and hippuric acid derivatives) was studied in
      rabbits, rats and mice. These compounds are eliminated in the kidney by
      glomerular filtration and undergo both tubular secretion and tubular
      reabsorption. For quantification of the effect of lipophilicity, an equation
      [formula: see text] was employed, where CLR represents renal clearance of the
      parent drug, ERPF is effective renal plasma flow, D is the partition coefficient
      of the acids between octanol and water, and a and b are constants. In
      interspecies comparison, the values of parameters a and b are similar indicating
      no significant interspecies differences in this route of elimination.

PMID- 1354734
TI  - Anorectic activity of fluoxetine and norfluoxetine in rats: relationship between
      brain concentrations and in-vitro potencies on monoaminergic mechanisms.
AB  - The present study was aimed at establishing the importance of brain monoamine
      uptake and release mechanisms in the anorectic activity of fluoxetine, relating
      them to the actual brain concentrations of the parent drug and its metabolite
      norfluoxetine after anorectic doses in rats. Both compounds showed anorectic
      activity when administered intraperitoneally, norfluoxetine being slightly more
      active (ED50 = 22.9 mumol kg-1) than fluoxetine (ED50 = 35.0 mumol kg-1) despite
      the fact that the metabolite is about ten times less potent than the parent drug
      in inhibiting 5-hydroxytryptamine (5-HT) uptake. Comparing the brain
      concentrations of norfluoxetine, in terms of maximum concentrations (Cmax) and
      area under the curve (AUC), after the ED50 of fluoxetine or synthetic
      norfluoxetine, it also appeared that the metabolite plays a major role in the
      anorectic effect of the parent drug in rats. Brain Cmax of fluoxetine (48.7
      microM) and norfluoxetine (21.7 and 27.3 microM after metabolite and drug,
      respectively) were several times those blocking 5-HT uptake in-vitro (0.5
      microM), making it unlikely that fluoxetine (directly or through its metabolite)
      reduces food intake by specifically blocking 5-HT neuronal uptake. Brain Cmax of
      fluoxetine but particularly norfluoxetine were more compatible with those capable
      in-vitro of affecting catecholaminergic mechanisms, such as inhibition of
      dopamine and noradrenaline uptake and enhancement of dopamine release. These
      results together with recent in-vitro findings that the parent compound and its
      active metabolite induce tritium release from hippocampal synaptosomes previously
      loaded with [3H]5-HT suggest that mechanisms other than inhibition of 5-HT uptake
      are involved in the anorectic action of these compounds in rats.

PMID- 1354736
TI  - Physiochemical interactions of praziquantel, oxamniquine and tablet excipients.
AB  - A differential scanning calorimetry and infrared spectrophotometry study of
      potential interactions between oxamniquine and praziquantel, two synergistic anti
      parasitic drugs, indicated that they did not interact on fusion. Mixtures of the
      two drugs with each of nine common pharmaceutical excipients (Ac-Di-Sol, Avicel,
      Crospovidone, calcium phosphate, magnesium stearate, starch, lactose, PEG 6000,
      stearic acid) appeared to interact only with stearic acid. These results
      suggested that a combination solid dosage form was feasible.

PMID- 1354737
TI  - Physicochemical properties of oxamniquine indicate a new polymorphic form.
AB  - New dissolution rate, chemical stability and thermal analysis data are reported
      for an anti-schistosomal drug, oxamniquine. A slow dissolution rate (40-70% in 1
      h) was found, which may contribute to its erratic clinical response. The drug was
      found to be chemically stable in water for at least 21 days at 37 degrees C.
      Dissolution rate and thermal analysis evidence is presented for a previously
      unreported polymorph (Form III). This form appears to be intermediate in physical
      stability between the known Forms I and II.

PMID- 1354738
TI  - Investigation of the 5-HT receptor mediating relaxation in guinea-pig proximal
      colon.
AB  - 5-Hydroxytryptamine (5-HT) induced concentration-related relaxations (EC50 = 9.1
      microM) of guinea-pig proximal colon pretreated with ketanserin (1 microM) and
      ondansetron (10 microM). This 5-HT-induced effect was neuronally mediated since
      it was blocked by tetrodotoxin (0.3 microM). 5-Carboxamidotryptamine was a full
      agonist and ten times more potent than 5-HT. alpha-Methyl-5-HT was a partial
      agonist. 2-Methyl-5-HT was without effect. Methysergide and metergoline were
      antagonists of 5-HT producing parallel shifts at 0.1 microM but unsurmountable
      antagonism at higher concentrations. pKB values of 8.0 and 7.3 were calculated
      for methysergide and metergoline, respectively. This study has identified a 5-HT
      induced relaxation of guinea-pig proximal colon which is mediated via a neuronal
      5-HT1-like receptor. However, the subtype has yet to be established.

PMID- 1354739
TI  - Haemolytic action of N-alkylpolymethylenediamines.
AB  - The haemolytic action of various N-alkyl derivatives (lauryl; C12H25-, myristyl;
      C14H29-, palmityl; C16H33-) of 1,3-diaminopropane, 1,4-diaminobutane, 1,5
      diaminopentate, 1,6-diaminohexane, 1,7-diaminoheptane, 1,8-diaminooctane was
      examined using rabbit red blood cells. The activities of the various derivatives
      were compared with those of antiplaque agents commonly used as mouthwashes;
      cetylpyridinium chloride (CP) and chlorhexidine acetate (CH). The haemolytic
      activities of these agents were dependent on the length of the N-alkyl chain,
      whereas the number of methylene groups between the nitrogen atoms had little
      effect. The order of potency was CP, N-palmityl derivatives, N-myristyl
      derivatives greater than N-lauryl derivatives greater than CH which was similar
      to the order of the antiplaque effect evaluated in-vitro.

PMID- 1354740
TI  - The use of albumin microspheres in the treatment of carrageenan-induced
      inflammation in the rat.
AB  - Free hydrocortisone, hydrocortisone incorporated into microspheres and empty
      microspheres have been administered orally to rats with carrageenan-induced
      hindpaw inflammation. Hydrocortisone administered in particles was effective at a
      lower dose than free steroid in reducing inflammation. Inflammatory exudates were
      able to release steroid from the microspheres by proteolytic degradation.

PMID- 1354741
TI  - Effects of morphine: an electrophysiological study on guinea-pig papillary
      muscle.
AB  - Intracellular microelectrodes were used to study the electrophysiological effects
      of morphine on guinea-pig papillary muscle. Morphine (5 x 10(-4) M) caused a
      significant decrease in the maximum rate of depolarization. At high
      concentrations (5 x 10(-3) M) morphine induced a decrease in the action potential
      amplitude and a prolongation of the action potential duration. The administration
      of naloxone (10(-7) M) partially antagonized the cardiac electrophysiological
      effects of morphine. These results suggest that the electrophysiological effects
      of morphine may be due to an interaction with opioid receptors.

PMID- 1354742
TI  - Inhibition by diltiazem of left ventricle collagen proliferation during
      renovascular hypertension development in rats.
AB  - Diltiazem administered in drinking water (0.7 mg mL-1) to Goldblatt two kidney
      one clip rats over 16 weeks did not prevent the development of hypertension and
      left ventricular hypertrophy (LVH). When the collagen content of the left
      ventricles was assayed (as hydroxyproline), it was found that the fibrosis,
      characteristic of LVH, was inhibited by diltiazem treatment, despite the fact
      that hypertension and LVH had developed. This study provides some indirect
      evidence for the notion that the collagen and myocyte compartments of the
      myocardium are under separate influences during LVH development in renovascular
      hypertension.

PMID- 1354743
TI  - Attempts to improve the Pharmacopoeial water-holding capacity test for absorbent
      dressings.

PMID- 1354744
TI  - Interaction of arteether with the red blood cell in-vitro and its possible
      importance in the interpretation of plasma concentrations in-vivo.

PMID- 1354746
TI  - International symposium: Automated analysis of radiation induced chromosome
      aberrations. Tokyo, July 3-4, 1991.

PMID- 1354745
TI  - Peptidergic regulation of the Limulus midgut.
AB  - 1. The morphology and innervation of the midgut (intestine) in the horseshoe
      crab, Limulus polyphemus was investigated. The organization of this tissue was
      examined with routine histology. Radioimmunoassay, immunohistochemistry and high
      performance liquid chromatography were employed to detect, localize and identify
      peptidergic innervation of the midgut. The actions of synthetic and native
      proctolin-like and FMRFamide-like peptides were compared on the isolated midgut
      preparation. 2. Levels of proctolin and FMRFamide were determined in extracts of
      Limulus midgut tissue using radioimmunoassay. High levels of proctolin-like
      immunoreactivity (69.5 +/- 11.3 ng/g) were detected, while levels of FMRFamide
      like immunoreactivity (0.8 +/- 0.2 ng/g) were less. Proctolin levels were equally
      distributed, while the levels of FMRFamide-like immunoreactivity exhibited an
      anterior bias. 3. Proctolin- and FMRFamide-like immunoreactivities in the Limulus
      midgut were localized with immunohistochemistry. Proctolin- and FMRFamide
      immunoreactive elements were detected in intestinal nerve branches and individual
      fibers running along the surface of the midgut in whole-mount preparations. In
      sectioned tissue, staining for these peptides was observed throughout the midgut,
      typically associated with muscle bands and fibers. Only a few immunoreactive cell
      bodies were observed. 4. Proctolin, and several FMRFamide-like peptides produced
      distinct and opposing actions on the isolated Limulus midgut preparation.
      Proctolin elicited contracture and rhythmic contractions of this tissue, while
      FMRFamide and N-terminally extended analogs of FLRFamide relaxed gut tension.
      FMRFamide-like peptides partially reversed the excitatory actions of proctolin.
      5. Proctolin- and FMRFamide-like peptides in Limulus midgut extracts were
      partially characterized with high performance liquid chromatography. One peak of
      proctolin-like activity was detected on a linear gradient of 18 to 31.5%
      acetonitrile. The native proctolin-like peptide produced excitatory actions on
      the isolated midgut preparation which were indistinguishable from those produced
      by synthetic proctolin. Several peaks of FMRFamide-like bioactivity (Busycon
      radula protractor muscle assay) were detected with a linear gradient of 5 to 30%
      acetonitrile. Fractions from two distinct peaks produced FMRFamide-like
      inhibitory effects on the isolated Limulus midgut preparation. These findings
      suggest a role for proctolin-like and FMRFamide-like peptides as regulators of
      intestinal motility in Limulus.

PMID- 1354747
TI  - Labelling of rat brain beta-adrenoceptors: (3H)CGP-12177 or
      (125I)iodocyanopindolol?
AB  - Binding of (125I)iodocyanopindolol (ICYP) and (3H)CGP-12177 to rat brain
      homogenates was characterized and compared. ICYP was shown to bind to both beta
      adrenergic and serotonin1B (5HT1B) receptors whereas (3H)CGP-12177 only labelled
      the first ones. The addition of 10 microM serotonin (5HT) prevented ICYP binding
      to 5HT receptors and under these experimental conditions both ligands labelled a
      similar total number of beta-adrenoceptors in the different rat brain regions.
      ICYP displayed a higher affinity for cerebellar (mainly beta 2-subtype) than for
      cerebral cortex beta-adrenoceptors (mainly beta 1-subtype) suggesting a subtype
      selectivity. A multiple displacement binding approach using CGP-20712A, a beta 1
      subtype ligand, as competitor revealed a 2.6 fold selectivity of ICYP for the
      beta 2-adrenoceptor subtype. On the other hand, (3H)CGP-12177 binds only to beta
      adrenoceptors and is not subtype selective in the rat brain homogenate.
      Considering both its high specificity and its lack of subtype selectivity (3H)CGP
      12177 seems to be a more suitable ligand than ICYP to non-selectively label beta
      adrenoceptors in rat brain.

PMID- 1354748
TI  - The revised Bethesda System for reporting cervical/vaginal cytologic diagnoses:
      report of the 1991 Bethesda workshop.

PMID- 1354749
TI  - Prenatal care and delivery in an agoraphobic woman. A case report.
AB  - Agoraphobia is a psychiatric illness that can cause patients to become
      functionally homebound. Although the obstetric care of women with agoraphobia has
      not been described previously, it is likely that the problem is more prevalent
      than recognized. A pregnant woman initially believed she would be unable to
      travel to the hospital for delivery. She was given prenatal care and
      psychotherapy at home; a safe hospital delivery was achieved. The management plan
      included the in-depth involvement of two physicians, physician preparation for a
      potential home delivery, patient education about obstetric risks and the
      harmlessness of agoraphobic panic attacks, and psychologic and marital therapy.
      Strategies for minimizing medicolegal risks were employed.

PMID- 1354750
TI  - N-(5,5-diacetoxypent-1-yl)doxorubicin: a new intensely potent doxorubicin
      analogue.
AB  - N-(5,5-Diacetoxypent-1-yl)doxorubicin (DAPDOX) (3), a new, water-soluble analogue
      of doxorubicin, has been synthesized by coupling doxorubicin with 5-oxopentane
      1,1-diacetate in the presence of NaBH3CN. This analogue was designed to be
      converted to the corresponding aldehyde, N-(5-oxopent-1-yl)doxorubicin, in the
      presence of carboxylate hydrolases, enzymes that are ubiquitous in tissue. DAPDOX
      had a half-life of several days in 0.05 M phosphate or 0.05 M acetate buffer
      solution at pH 4.0. However, in 0.05 M phosphate buffer at pH 7.4 in the presence
      of 20 unit equiv of porcine liver carboxylate esterase, the half-life of DAPDOX
      was less than 1 min. N-(5-acetoxypent-1-yl)doxorubicin (4), which should give
      rise to N-(5-hydroxypent-1-yl)doxorubicin on esterase-mediated hydrolysis, and N
      (pent-1-yl)doxorubicin (5), were also prepared for comparative biological
      studies. DAPDOX was 150 times more potent than doxorubicin at inhibiting the
      growth of Chinese hamster ovary (CHO) cells in culture. The compound retained the
      same degree of potency against a CHO subline 100-fold resistant to doxorubicin
      (CHO/DOX) that expressed elevated levels of P-glycoprotein. Compounds 4 and 5, on
      the other hand, were no more effective than doxorubicin at inhibiting the growth
      of CHO cells and were 4-7-fold less potent against the CHO/DOX subline. DAPDOX is
      representative of a new structural class of doxorubicin analogues with unique
      chemical and biological properties.

PMID- 1354751
TI  - Novel thiosemicarbazones derived from formyl- and acyldiazines: synthesis,
      effects on cell proliferation, and synergism with antiviral agents.
AB  - The synthesis of a series of novel thiosemicarbazones (TSC's) derived from
      various alkyl diazinyl (3-pyridazinyl, 4-pyrimidinyl, 2-pyrazinyl) ketones and 3
      pyridazinecarbaldehyde and their evaluation against herpes simplex virus (HSV)
      and human immunodeficiency virus (HIV) as well as the determination of their
      cytotoxicity are described. In addition, the effects of combination of such TSC's
      with the well-known antiviral drugs acyclovir (ACV) and 3'-azido-3'
      deoxythymidine (AZT) were studied. Under our experimental conditions, i.e.
      determination of virus-induced cytopathic effect upon infection of HUT78 cells
      with HSV-1 and upon infection of MT4 cells with HIV-1, no antiviral activity
      could be detected with any of the TSC's. However, pronounced effects on
      proliferation of these rapidly growing T4 lymphocyte cell lines were observed.
      Clear structure-activity relationships with regard to these cytotoxic effects
      could be established: compared to pyridine, pyrazine, or pyrimidine-derived TSC's
      most of the 3-pyridazinyl congeners investigated are less cytotoxic; introduction
      of a methyl group into C-6 of the pyridazine system or prolongation of the acyl
      moiety in these compounds has essentially no influence; all compounds bearing an
      N,N-dimethylamino or a cycloamino substituent are much more toxic than those with
      an NH2 or NHR substituent; the nature of R in the latter type of compounds has
      only moderate influence. It has been reported that combination of TSC's with the
      antiviral agent acyclovir (ACV) results in potentiation of this well-known drug.
      We evaluated the potential of our series of novel TSC's in combination with ACV
      for inhibition of HSV-1-induced cytopathic effect in HUT78 cells and in
      combination with 3'-azido-3'-deoxythymidine (AZT) for inhibition of HIV-1-induced
      cytopathic effect in MT4 cells. Only four compounds out of this series, all
      characterized by an unsubstituted NH2 group, exhibited moderate synergism with
      the above mentioned antiviral drugs. Our results do not support the previously
      expressed opinion that TSC's are selective antiviral agents. In our test systems
      no evidence for inhibition of virus-induced cytopathic effect was obtained. The
      TSC derivatives exhibited a broad range of cytotoxic effects, some at
      concentrations considerably below those reported to have antiviral efficacy.
      Several of our novel diazine-derived compounds proved advantageous over the
      previously described pyridine analogues with regard to cytotoxicity. Moderate
      synergism could be detected for relatively noncytotoxic TSC's with the antiviral
      drugs ACV (antiherpes) and AZT (anti-HIV).

PMID- 1354753
TI  - Does transurethral laser ureterolithotripsy justify its cost?
AB  - A prospective consecutive series of 64 patients who underwent transurethral laser
      ureterolithotripsy using a 7.2F semirigid ureteroscope was compared to the
      immediately preceding consecutive series of 98 patients who had undergone
      ultrasound lithotripsy using rigid 9.5F or 12.5F ureteroscopes. The distribution
      of the calculi by size and composition in both series was similar. There was a
      higher proportion of upper ureteral calculi in the laser lithotripsy series. The
      success rate for a first attempt at laser lithotripsy was 92.2% versus 71.4% for
      the ultrasound series (p less than 0.01). When the stone could be reached
      ultrasound and laser lithotripsy had a fragmentation rate of 97%. The principal
      reason for the difference in results was the poorer ability to reach calculi when
      using the larger rigid ureteroscopes. One patient who had failed ultrasound
      lithotripsy was successfully treated with laser lithotripsy a year later. The
      overall morbidity was less for laser lithotripsy. The 3-year cost-benefit
      analysis revealed a smaller difference in cost than expected and the 5-year
      analysis was advantageous for laser lithotripsy because of its higher success
      rate. Savings were also realized in the laser series because of the higher
      proportion of subjects treated as outpatients, and a lower mean duration of
      hospitalization and time missed from work. For our center with an annual work
      load of approximately 100 cases laser lithotripsy achieved a superior cost
      benefit ratio.

PMID- 1354752
TI  - Development of renal toxicity in F344 rats gavaged with mercuric chloride for 2
      weeks, or 2, 4, 6, 15, and 24 months.
AB  - Both sexes of F344 rats were gavaged with maximal tolerated doses of mercuric
      chloride for periods from 2 wk to up to 2 yr to investigate chronic
      nephrotoxicity and potential carcinogenicity. The toxicity of mercuric chloride
      was excessive after 2 wk of exposure to doses ranging from 1.25 to 20 mg/kg,
      compromising renal function by selectively destroying cells of the proximal
      tubules, and eliciting marked elevations in urinary biomarker enzymes diagnostic
      for acute renal tubule necrosis. In the 2-wk studies, urinary alkaline
      phosphatase and aspartate amino-transferase were most sensitive to renal mercury
      toxicity among a panel of six enzymes, exhibiting twofold increases above
      controls at the 5.0 mg/kg dose, before changes in the other enzymes occurred.
      Urinary lactate dehydrogenase was the most responsive enzyme, with up to 11-fold
      increases in activity above controls. In response to mercuric chloride exposure
      of 5.0 mg/kg for 2-6 mo, the greatest and most persistent increases in elevation
      of urinary enzyme activities were exhibited by alkaline phosphatase and gamma
      glutamyl transferase, which increased two-to threefold above controls. At this
      interval, the maximal severity of the renal lesions in both sexes of rats was
      graded as minimal to mild. Beyond 6 mo none of the urinary enzymes measured in
      this study was adequate as biomarkers of nephrotoxicity, although the severity of
      the renal lesions had progressed. Mercury accumulated in a dose-related fashion
      primarily in the kidney, and to a lesser extent in the liver. The severity of the
      renal lesions was increased by continued exposure to mercuric chloride, as tissue
      concentrations of mercury rose in proportion to dose. Mercuric chloride treatment
      for 2 yr clearly exacerbated the severity of the spontaneous nephrotoxicity
      prevalent in aging F344 rats. The excessive mortality that occurred in the male
      rats was probably due to a combination of these factors. No renal tumors were
      detected in rats, possibly because the potential for their development was
      reduced; however, direct tissue contact with mercury induced squamous-cell
      papillomas of the forestomach in both sexes.

PMID- 1354754
TI  - Still a mystery but 'not likely' a virus.

PMID- 1354755
TI  - From the Centers for Disease Control. Update: CD4+ T-lymphocytopenia in persons
      without evident HIV infection--United States.

PMID- 1354756
TI  - From the Centers for Disease Control. Unexplained CD4+ T-lymphocyte depletion,
      persons without evident HIV infection.

PMID- 1354757
TI  - [Treatment of leukemia and malignant lymphoma of children by autologous
      circulating stem cell transplantation--evaluation of 57 cases by a multicenter
      study].

PMID- 1354758
TI  - [Autologous peripheral blood stem cell transplantation--an evaluation in adults].

PMID- 1354759
TI  - [Clinical applications of ion-sensor].
AB  - The coulometric measurement technique offers a rapid, accurate and precise method
      for measuring iron in liquid samples. It is well-known that analytical
      interferences common to colorimetric methods essentially do not exist in this
      procedure. However, this study shows that various drugs, such as chondroitin iron
      sulfate, deferoxamine mesylate, and salazosulfapyridine have strongly positive
      effects on the most contemporary determination of serum iron. The study of the
      analytical interference of drugs is important for precise and accurate
      measurement of desirable or undesirable pharmacological effects. New drugs and
      new methods should be systematically studied in this manner.

PMID- 1354760
TI  - L-365,260, a potent CCK-B/gastrin receptor antagonist, suppresses gastric acid
      secretion induced by histamine and bethanechol as well as pentagastrin in rats.
AB  - We evaluated the effects of a potent cholecystokinin (CCK)-B/gastrin receptor
      antagonist, L-365,260 (3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4
      benzodiazepin - 3-yl)-N'-( 3-methylphenyl) urea); a selective CCK-A receptor
      antagonist, devazepide (L-364,718); and cimetidine on gastric acid secretion
      induced by pentagastrin, histamine and bethanechol in anesthetized rats. We also
      evaluated the effects of L-365,260 and cimetidine on acid secretion in pylorus
      ligated rats. Intravenous administration of L-365,260, L-364,718 and cimetidine
      dose-dependently reduced acid secretion induced by pentagastrin (20 nmol/kg/hr),
      with ED50 values of 0.63, 19.1 and 2.5 mumol/kg, respectively. Of interest was
      the finding that L-365,260, like cimetidine, dose-dependently inhibited acid
      secretion induced by histamine (100 mumol/kg/hr) and bethanechol (5 mumol/kg/hr)
      with ED50 values of 5.9 and 4.3 mumol/kg, respectively. L-364,718, even at 30
      mumol/kg, i.v., had only a slight effect on histamine- or bethanechol-induced
      acid secretion. Gastric acid secretion was suppressed by treatment with L-365,260
      (3-100 mumol/kg, i.v.) and cimetidine (11.9-396.4 mumol/kg, i.v.) in pylorus
      ligated rats, with ED50 values of 13.3 and 96.9 mumol/kg, respectively. These
      results indicate that L-365,260 suppresses acid secretion induced by histamine
      and bethanechol in rats and that the gastrin receptor plays an important role in
      acid secretion in pylorus-ligated rats.

PMID- 1354762
TI  - Proceedings of the International Symposium "Smooth Muscle". Fukuoka, Japan,
      January 29-February 1, 1992.

PMID- 1354761
TI  - Selectivity of bevantolol hydrochloride towards alpha- and beta-adrenoceptor
      subtypes in rat cerebral cortex.
AB  - Selectivity of bevantolol hydrochloride (NC-1400) towards alpha- and beta
      adrenoceptor subtypes of rat cerebral cortex was examined in binding experiments
      and compared with propranolol. Bevantolol biphasically displaced the 3H
      dihydroalprenolol binding. The affinity of bevantolol to beta 1-adrenoceptor was
      equal to that of propranolol. Bevantolol displaced 3H-prazosin binding
      monophasically but not 3H-p-aminoclonidine binding. These results suggest that
      bevantolol is a beta 1-adrenoceptor antagonist with a relatively high affinity to
      alpha 1-adrenoceptor subtypes.

PMID- 1354763
TI  - Noradrenaline-ATP cotransmission: operation in blood vessels and cotransmitter
      release ratios.

PMID- 1354764
TI  - Mechanism of action of nitric oxide: heme-dependent activation of guanylate
      cyclase represents a unifying signal transduction mechanism.

PMID- 1354765
TI  - Nitric oxide as a non-adrenergic, non-cholinergic neurotransmitter in the
      gastrointestinal tract.

PMID- 1354766
TI  - Interactions of R(+)- and S(-)-isomers of beta-adrenergic partial agonists with
      the high affinity site of beta-adrenoceptors.

PMID- 1354767
TI  - Intracellular calcium changes induced by alpha 1-receptor stimulation in guinea
      pig vas deferens.

PMID- 1354768
TI  - Nitric oxide is the likely inhibitory neurotransmitter of erection in the human
      penis.

PMID- 1354769
TI  - Effects of L-nitroarginine on alpha-agonists-induced contraction of Wistar Kyoto
      rats.

PMID- 1354770
TI  - Nitric oxide (NO) as non-adrenergic non-cholinergic neurotransmitter in human
      corpus cavernosum.

PMID- 1354771
TI  - Serotonergic mechanisms in anxiolytic effect of tandospirone in the Vogel
      conflict test.
AB  - To clarify which 5-HT1A receptors, autoreceptors located in the raphe nuclei or
      post-synaptic receptors in the forebrain areas receiving a 5-HT input, mediate
      the anticonflict action of tandospirone (a 5-HT1A receptor-related anxiolytics),
      the behavioral effects of tandospirone were studied in 5,7-dihydroxytryptamine
      (5,7-DHT) treated rats. By measuring both monoamines and their metabolite levels
      and densities of [3H]8-OH-DPAT binding in 5,7-DHT-treated rat brain, we confirmed
      that pretreatment with 5,7-DHT destroyed 5-HT neurons selectively without
      affecting postsynaptic 5-HT1A receptors located on the postsynaptic neurons. This
      selective destruction produced no significant changes in the drinking behavior of
      rats in either punished or unpunished sessions of the Vogel conflict test.
      Furthermore, this destruction altered neither the effect of tandospirone on
      punished responding in this procedure nor the potency of tandospirone to induce a
      flat body posture in rats, which is known as the "serotonin behavioral syndrome".
      These results suggested that the anticonflict action of tandospirone may be
      produced, at least in part, by binding to postsynaptic 5-HT1A receptors and
      activating them as agonists, and not to 5-HT1A autoreceptors located on the cell
      bodies of 5-HT neurons.

PMID- 1354773
TI  - [Differentiation and maturation of excurrent duct system of rat testes].
AB  - The present study was designed to investigate relations of gamma-Glutamyl
      transpeptidase (gamma-GTP) activities to morphological differentiation and
      maturation of rat testicular excurrent duct system including rete testis,
      efferent ductuli and epididymal ducts. Animals used were Wistar rats aged from 3
      days to 12 weeks. Histochemical demonstration of gamma-GTP activities was carried
      out by the method of Rutenburg et al. (1969). Morphological differentiation of
      the epithelium and structure of the rete testis occurred between 2 and 3 weeks
      and completed by the age of 6 weeks, which was accompanied by induction and
      deletion of gamma-GTP activity. Morphological differentiation and maturation of
      the epithelium of the efferent ductuli and the epididymal ducts became evident by
      the age of 4 weeks and gamma-GTP was active in both epithelial cells throughout
      the period examined. Since the maturation of rete testis epithelium was found to
      proceed as observed as Sertoli cells, the origin and functions of the rete testis
      epithelium and Sertoli cells are considered to be identical. The simultaneous
      development of the efferent ductuli and the epididymal ducts suggests that both
      tissues originate from mesonephric ducts and have similar functions, although
      mature epithelial cells of both tissues are completely different.

PMID- 1354772
TI  - Sympathetic nerve stimulation activates both beta 1- and beta 2-adrenoceptors of
      SA and AV nodes in anesthetized dog hearts.
AB  - We investigated blocking effects of the selective beta 1-adrenoceptor blocker
      atenolol (0.1-100 micrograms/kg, i.v.), the selective beta 2-adrenoceptor blocker
      ICI 118,551 (1-1000 micrograms/kg, i.v.) and the combination of the two drugs on
      positive chronotropic and dromotropic responses to norepinephrine (NE) released
      by stimulation of the sympathetic nerves in anesthetized, neurally decentralized,
      open-chest dogs after atropine was given. Stimulation of the intracardiac
      sympathetic nerves to the SA nodal region or to the AV nodal region selectively
      increased heart rate or decreased AV conduction time, respectively. ICI 118,551
      inhibited the chronotropic or dromotropic response to each stimulation in a dose
      dependent manner, but its inhibition of the dromotropic response was less than
      that of the chronotropic response. Atenolol similarly inhibited either the
      positive chronotropic or dromotropic response to each stimulation in a dose
      related manner. The combination of atenolol and ICI 118,551 attenuated the
      responses to each stimulation more than atenolol alone. These data indicate that
      sympathetic nerve stimulation activates both beta 1- and beta 2-adrenoceptors of
      the SA and AV nodes and that the proportion of beta 2-adrenoceptor-mediated
      effects on the AV node is less than that on the SA node. These results suggest
      that neurally released NE in part controls physiological functional cardiac
      responses mediated through beta 2-adrenoceptors, in addition to the responses
      predominantly mediated through beta 1-adrenoceptors.

PMID- 1354775
TI  - [Reflex delay of urination in a patient with hemorrhagic fever with renal
      syndrome].

PMID- 1354774
TI  - [Pulmonary edema in patients with hemorrhagic fever with renal syndrome].
AB  - Eight patients suffering from hemorrhagic fever with renal syndrome (HFRS)
      running a severe course complicated by pulmonary edema developed absolute
      hyperhistaminemia and hyperserotoninemia, histamine and serotonin accumulation in
      tissues. These amines inactivation in blood and lungs and excretion of
      catecholamines with urine got disturbed. High blood and lung tissue levels of
      biologically active substances resultant in enhanced permeability of the vascular
      wall and alveolar epithelium, hemodynamic disturbances due to hypoexcretory
      hypercatecholaminemia are thought to underlie the occurrence of this grave HFRS
      complication.

PMID- 1354776
TI  - Measurement of free cytosolic calcium in single cells: method and application.
AB  - Intracellular calcium [Ca2+]i acts as an important intracellular messenger system
      for secretion and synthesis, cell growth and differentiation. In order to
      demonstrate definitively that a change in [Ca2+]i is responsible for a
      physiological event, one has to measure [Ca2+]i directly within intact cells and
      correlate the time course of any [Ca2+]i changes with the biological response.
      Measurement of [Ca2+]i was done in a single cell preloaded with fluorescent Ca
      indicator fura2 using a fluorescent unit (lonoquant) consisting of an inverted
      microscope (Zeiss IM 35) equipped with a mercury lamp and a rotating filter wheel
      containing filters at wavelengths of 340 and 380 nm. Cells were alternately
      excited and emission signals of fura 2-loaded cells were collected by a
      photomultiplier and recorded on-line on a computer screen. As a model system, the
      rat C-cell carcinoma cell line rMTC 6-23 secreting calcitonin was used. An acute
      elevation of extracellular calcium resulted in an increase in [Ca2+]i within 5
      sec and rapid release of preformed calcitonin. This tight linkage between
      extracellular calcium and [Ca2+]i is mediated via Ca influx through voltage
      dependent Ca channels. These channels are modulated by intracellular cAMP,
      yielding a rhythmic oscillation of [Ca2+]i, as well as by extracellular
      somatostatin blocking the Ca channel and the increase of [Ca2+]i via a pertussis
      toxin sensitive Gi protein. The change in [Ca2+]i is associated with changes in
      calcitonin secretion, confirming the stimulus secretion coupling via voltage
      dependent Ca channels in C-cells.

PMID- 1354777
TI  - [Clozapine--an atypical neuroleptic with a unique clinical profile].

PMID- 1354778
TI  - [Five points for better treatment of alcoholics in health care services].

PMID- 1354779
TI  - [Yaws and influenza in Columbus' baggage to the new world].

PMID- 1354780
TI  - [Adrenergic beta 2-agonists are to be considered more as friends than enemies].

PMID- 1354781
TI  - Coeliac disease, epilepsy, and cerebral calcifications. The Italian Working Group
      on Coeliac Disease and Epilepsy.
AB  - There have been anecdotal reports of an association between coeliac disease and
      epilepsy with cerebral calcifications that resemble those of the Sturge-Weber
      syndrome. A series of patients who had epilepsy with calcifications, in whom
      coeliac disease (CD) was incidentally observed, prompted us to study this
      association. 43 patients (15 male, age range 4.6-30.7 years) were selected from
      two series. 31 patients with cerebral calcifications of unexplained origin and
      epilepsy (series A) underwent intestinal biopsy. 12 patients with CD and epilepsy
      (series B) underwent computed tomography. Antibodies to gluten, folic acid serum
      concentrations, were measured, and HLA typing was done in most patients. 24 of
      the series A patients were identified as having CD on the basis of a flat
      intestinal mucosa (15/22 with a high concentration of serum antigluten), and 5
      series B patients showed cerebral calcifications, giving a total of 29 cases with
      the combination of CD, epilepsy, and cerebral calcifications (CEC). In 27 of
      these CEC patients, calcifications were located in the parieto-occipital regions.
      Only 2 of the series A patients had gastrointestinal symptoms at the time of
      intestinal biopsy; most patients had recurrent diarrhoea, anaemia, and other
      symptoms suggestive of CD in the first 3 years of life. The epilepsy in CEC
      patients was poorly responsive to antiepileptic drugs. Gluten-free diet
      beneficially affected the course of epilepsy only when started soon after
      epilepsy onset. Cases of "atypical Sturge-Weber syndrome" (characterised by
      serpiginous cerebral calcifications and epilepsy without facial port-wine naevus)
      should be reviewed, and CD should be ruled out in all cases of epilepsy and
      cerebral calcifications of unexplained origin.

PMID- 1354782
TI  - Primary pancreatic beta-cell secretory defect caused by mutations in glucokinase
      gene in kindreds of maturity onset diabetes of the young.
AB  - Maturity-onset diabetes of the young (MODY), characterised by non-insulin
      dependent diabetes mellitus (NIDDM) with an early age of onset, is a genetically
      heterogeneous disorder. In most MODY kindreds described in France, chronic
      hyperglycaemia is caused by mutations in the gene encoding pancreatic beta-cell
      and liver glucokinase (GCK). We here report the beta-cell secretory profiles of
      nine patients from four GCK-linked MODY kindreds. First-phase insulin secretion
      assessed by an intravenous glucose test was comparable in patients and seven
      controls. However, beta-cell secretory response to continuous glucose stimulus
      during a hyperglycaemic glucose clamp was significantly reduced: mean plasma
      insulin values of 12 (SD 7) vs 40 (11) mU/l (p = 0.0001) and mean plasma C
      peptide values 1.20 (0.30) vs 2.61 (0.37) (p = 0.0001). This secretory profile is
      different from those for NIDDM with late age of onset or MODY not linked to GCK.
      Fasting plasma insulin and C-peptide in patients were inappropriately low in
      relation to concomitant plasma glucose level. Furthermore, during a
      hyperinsulinaemic euglycaemic clamp, endogenous insulin secretion at euglycaemia
      (5 mmol/l) was suppressed in patients but not in controls. These results suggest
      that mutant GCK may lead to chronic hyperglycaemia by raising the threshold of
      circulating glucose level which induces insulin secretion. These data provide the
      first demonstration of a primary pancreatic secretory defect associated with a
      form of NIDDM.

PMID- 1354783
TI  - Immunodeficiency presenting as hypergammaglobulinaemia with IgG2 subclass
      deficiency.
AB  - Recurrent bacterial infections, lymphadenopathy, and failure to thrive are
      unlikely to be attributed to immune deficiency if they occur in the presence of
      hypergammaglobulinaemia, and other explanations will usually be sought. We
      describe eight patients who presented with all these features in infancy or early
      childhood. Deficiencies of immunoglobulin and antibody production were initially
      discounted, and the children were referred for investigation of possible
      lymphoma, autoimmune disease, or chronic viral infection. The patients were later
      referred to us for more detailed immunological investigation, which revealed low
      levels of IgG2 and poor specific antibody production to common pathogens.
      Treatment with intravenous immunoglobulin resulted in resolution of signs and
      symptoms in all patients. Thus we have shown that hypergammaglobulinaemia does
      not preclude the presence of immunoglobulin/antibody deficiency. We suggest that
      investigation of children with high levels of IgG and features of
      immunodeficiency should include IgG subclass analysis.

PMID- 1354784
TI  - Filovirus clearance in non-human primates.
AB  - There has been concern in the USA and Europe about filovirus outbreaks in
      recently imported monkeys, and possible transmission to human beings. Healthy
      monkeys have been found to have low-titre immunofluorescence antibody (IFA) to
      Asian filoviruses (Reston and Pennsylvania viruses) as well as to the African
      filoviruses that caused fulminating human outbreaks in the 1970s (Ebola [Zaire]
      and Sudan viruses). We have assessed whether such monkeys are a risk to man. We
      studied 42 non-human primates; 31 were experimentally infected with African and
      Asian filoviruses, 6 were infected during a documented Reston filovirus outbreak,
      and 5 had serological evidence suggestive of recent filovirus infection. During
      the first 15 days after infection, virus could be routinely recovered from serum
      or biopsy or necropsy tissue, and Asian filovirus RNA could be detected by
      polymerase chain reaction. 20 to 600 days after challenge, filovirus could no
      longer be recovered nor viral RNA detected in 141 serum, liver, spleen, or kidney
      specimens. Animals surviving filovirus infection develop high-titre, cross
      reacting filovirus-specific antibody 14 to 21 days after infection, and this
      coincides with virus clearance. Healthy monkeys with low-titre filovirus antibody
      may be regarded as uninfected.

PMID- 1354785
TI  - Low cerebrospinal-fluid concentrations of soluble amyloid beta-protein precursor
      in hereditary Alzheimer's disease.
AB  - In Alzheimer's disease, deposits of amyloid beta-protein are apparently derived
      from intracellular processing of a large precursor protein. We have measured
      concentrations of this precursor in cerebrospinal fluid (CSF) from six members of
      a family affected by presenile Alzheimer's disease associated with a point
      mutation of the precursor gene. One gene carrier with clinical signs of the
      disorder had low CSF concentrations of the precursor, similar to those of three
      patients with sporadic Alzheimer's disease subsequently confirmed at necropsy.
      Two symptom-free gene carriers had CSF precursor concentrations similar to those
      of non-demented controls, though the value was lower in one, who had deficits
      revealed on neuropsychological testing, than in the other. These findings suggest
      that low concentrations of soluble amyloid precursor proteins in the CSF reflect
      the process that results in amyloid plaque formation and vascular deposition in
      Alzheimer's disease.

PMID- 1354786
TI  - Genetic basis of NIDDM.

PMID- 1354787
TI  - Cardiopulmonary resuscitation, AIDS, and public panic.

PMID- 1354788
TI  - Rubbish!

PMID- 1354789
TI  - Charging for health services in the Third World.

PMID- 1354790
TI  - Lymphocyte traffic.

PMID- 1354791
TI  - Pathogenesis of non-insulin-dependent diabetes mellitus in the black population
      of southern Africa.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is an important health problem in
      the black population of southern Africa. Whether the primary cause of NIDDM is
      insulin secretory dysfunction or peripheral insulin resistance is unknown. In
      westernised populations it is believed that insulin resistance and
      hyperinsulinaemia occur in the early stages of disease, followed later by
      progressive impairment of insulin secretion. However, we suggest that in the
      southern African black population a decrease in the mass of functioning beta
      cells is an important event, making these people vulnerable to the deleterious
      effects of insulin resistance induced by obesity and other factors. These
      abnormalities are, in turn, associated with insulin receptor down-regulation. An
      accelerated decline in beta-cell function then follows in susceptible
      individuals, ultimately producing striking insulinopenia. Insulinopenic NIDDM in
      black southern Africans may partly explain why this population has a
      comparatively low incidence of macrovascular complications and also predicts a
      short-lived therapeutic response to oral sulphonylureas in most patients.

PMID- 1354792
TI  - Impact of user fees on attendance at a referral centre for sexually transmitted
      diseases in Kenya.
AB  - We investigated the impact of a short-lived policy of charging fees to patients
      attending public-sector outpatient health facilities in Kenya by collecting data
      on attendance at Nairobi's Special Treatment Clinic for sexually transmitted
      diseases (STDs) before (23 months), during (9 months), and after (15 months) the
      user-charge period. During the user-charge period, the seasonally adjusted total
      mean monthly attendance of men decreased significantly to 40% (95% CI 36-45) of
      that before fees were levied. Attendance rose in the post-user-charge period, but
      reached only 64% (59-68) of the pre-user-charge level. For women, the adjusted
      total mean monthly attendance during the user-charge period was reduced
      significantly to 65% (55-77) of the pre-user-charge level. Mean monthly
      attendance by women rose in the post-user-charge period to 22% (9-37) above the
      pre-user-charge level. There was no evidence of an increase in attendance over
      the course of the user-charge period among either men or women. The introduction
      of user fees probably increased the number of untreated STDs in the population,
      with potentially serious long-term health implications. The user-fee experience
      in Kenya should be carefully evaluated before similar measures are introduced
      elsewhere.

PMID- 1354793
TI  - The role of amyloid beta-protein in Alzheimer's disease.
AB  - Deposition of amyloid beta-protein in the brain has been regarded as the central
      event in Alzheimer's disease; however, amyloid beta-protein precursor is an
      endogenous protein, probably with neurotrophic functions. An alternative
      hypothesis is that amyloid beta-protein is involved in the disease process
      secondarily, as a protective reactant when brain cells are injured. Insufficiency
      of amyloid beta-protein precursor, whether because of a genetic defect or in
      relation to the action of environmental factors, then allows development of
      Alzheimer changes.

PMID- 1354795
TI  - Research faces a rare budget slump.

PMID- 1354794
TI  - In defence of insulin: a critique of syndrome X.

PMID- 1354796
TI  - HIV-negative AIDS.

PMID- 1354797
TI  - Transplantation 1992.

PMID- 1354798
TI  - Zambia: drought in Monze.

PMID- 1354799
TI  - US growth hormone trials to be reviewed.

PMID- 1354800
TI  - HIV prevention and homosexual men.

PMID- 1354801
TI  - Prognostic factors in medulloblastoma.

PMID- 1354802
TI  - Diagnosis of recurrent suffocation of children.

PMID- 1354803
TI  - Diagnosis of recurrent suffocation of children.

PMID- 1354804
TI  - Inappropriate sensor application in pulse oximetry.

PMID- 1354805
TI  - Attack rate of exanthem subitum in Japan.

PMID- 1354806
TI  - Intrauterine transmission of human herpesvirus 6.

PMID- 1354807
TI  - Dietary magnesium and prediction of heart disease.

PMID- 1354808
TI  - Striking identity between HIV-1 envelope glycoprotein gp120 and its CD4 receptor.

PMID- 1354809
TI  - AIDS minus HIV?

PMID- 1354810
TI  - Lack of activity of zidovudine against Ureaplasma urealyticum and Mycoplasma
      hominis.

PMID- 1354811
TI  - Origin of HIV-1.

PMID- 1354812
TI  - Effect of type of haematology analyser on CD4 count.

PMID- 1354813
TI  - Cerebral MRS in infant with suspected Reye's syndrome.

PMID- 1354814
TI  - Comparisons of olsalazine and mesalazine in prevention of relapse in ulcerative
      colitis.

PMID- 1354815
TI  - Serum L-arginine in hypercholesterolaemia.

PMID- 1354816
TI  - Recording of outpatient consultations.

PMID- 1354817
TI  - Recording of outpatient consultations.

PMID- 1354818
TI  - Vitamin A deficiency and childhood mortality.

PMID- 1354819
TI  - Soft tissue sarcoma, aplastic anaemia, and exposure to pesticides.

PMID- 1354820
TI  - Midwife's view of reports on maternity services.

PMID- 1354821
TI  - Vincristine for thrombotic thrombocytopenic purpura.

PMID- 1354822
TI  - Screening for cystic fibrosis carriers.

PMID- 1354823
TI  - Thrombolysis for postoperative pulmonary embolism.

PMID- 1354824
TI  - Thrombolysis for postoperative pulmonary embolism.

PMID- 1354825
TI  - Excessive megakaryocyte migration after thrombolytic therapy and benefit of
      aspirin with streptokinase.

PMID- 1354827
TI  - Helicobacter pylori infection in early infancy.

PMID- 1354828
TI  - Rapid interphase FISH diagnosis of trisomy 18 on blood smears.

PMID- 1354826
TI  - Magnetic resonance imaging of the hepatic veins in split liver transplantation.

PMID- 1354829
TI  - Isotretinoin and the axial skeleton.

PMID- 1354831
TI  - Retraction: effects of interleukin-1 on platelet counts.

PMID- 1354830
TI  - Neurological symptoms associated with cyclosporin plus doxorubicin.

PMID- 1354832
TI  - The POT1 gene for yeast peroxisomal thiolase is subject to three different
      mechanisms of regulation.
AB  - The Saccharomyces cerevisiae POT1 gene is, as are other yeast peroxisomal protein
      genes, inducible by fatty acids and repressible by glucose. We have now found
      that it is also induced during the stationary phase of the culture. To
      investigate these three regulatory circuits, we have studied the mRNA levels of
      regulatory mutants as well as the changes in chromatin structure upon gene
      activation. We conclude that the regulation of transcriptional activity in
      glucose repression, oleate induction, and stationary phase induction follow
      different molecular mechanisms. We suggest that this multiplicity of regulatory
      mechanisms may represent a general rule for the yeast peroxisomal protein genes.

PMID- 1354833
TI  - PulO, a component of the pullulanase secretion pathway of Klebsiella oxytoca,
      correctly and efficiently processes gonococcal type IV prepilin in Escherichia
      coli.
AB  - The PulO protein required for extracellular secretion of pullulanase by
      Klebsiella oxytoca is known to be highly homologous to two type IV prepilin
      peptidases, namely XcpA(PilD) (Pseudomonas aeruginosa) and TcpJ (Vibrio
      cholerae). The predicted prepilin peptidase activity of PulO was confirmed by
      showing that it could correctly process the product of the cloned pilE.1 type IV
      pilin structural gene from Neisseria gonorrhoeae in Escherichia coli. The P.
      aeruginosa prepilin peptidase and another putative prepilin peptidase, ComC from
      Bacillus subtilis, also processed prePilE. Subcellular fractionation showed that
      the pilE gene product that had been processed by PulO remained associated with
      the cytoplasmic membrane, as did the unprocessed precursor. PulO was also shown
      to process three of the four prePilE-PhoA hybrids tested. Southern hybridization
      experiments suggest that a pulO homologue is present in the N. gonorrhoeae
      chromosome.

PMID- 1354834
TI  - Mycobacteria contain two groEL genes: the second Mycobacterium leprae groEL gene
      is arranged in an operon with groES.
AB  - In contrast to other bacterial species, mycobacteria were thus far considered to
      contain groEL and groES genes that are present on separate loci on their
      chromosomes, Here, by screening a Mycobacterium leprae lambda gt11 expression
      library with serum from an Ethiopian lepromatous leprosy patient, two DNA clones
      were isolated that contain a groEL gene arranged in an operon with a groES gene.
      The complete DNA sequence of this groESL operon was determined. The predicted
      amino acid sequences of the GroES and GroEL proteins encoded by this operon are
      85-90% and 59-61% homologous to the sequences from previously characterized
      mycobacterial GroES and GroEL proteins. Southern blotting analyses with M. leprae
      groES- and groEL-specific probes demonstrate that similar groESL homologous DNA
      is present in the genomes of other mycobacteria, including Mycobacterium
      tuberculosis. This strongly suggests that mycobacteria contain a groESL operon in
      addition to a separately arranged second groEL gene. Using five T-cell clones
      from two leprosy patients as probes, expression of the M. leprae GroES protein in
      Escherichia coli after heat shock was demonstrated. Four of these clones
      recognized the same M. leprae-specific GroES-derived peptide in a DR2-restricted
      fashion. No expression of the groEL gene from this operon was detected in E. coli
      after heat shock, as tested with a panel of T-cell clones and monoclonal
      antibodies reactive to previously described GroEL proteins of mycobacteria.

PMID- 1354835
TI  - [Age-related changes in mosquito insecticide resistance and their relation to the
      mechanisms of detoxication].
AB  - The mechanisms of DDT, permethrin and malathion resistance were determined
      indirectly by means of synergists inhibiting the detoxification enzymes. It was
      found that metabolic resistance dependent on glutathione-S-transferase, MFO and
      carboxylesterase is the most liable to age changes. Such changes are less
      expressive in mosquitos which have supposedly kdr-resistance. In young mosquitos
      (1-2 days) of all species, the rate of synergism is relatively low and fails to
      explain high resistance which is usual for juvenile specimen.

PMID- 1354836
TI  - [The efficacy of a combined preparation based on Bacillus sphaericus and Bac.
      thuringiensis H-14 against the larvae of blood-sucking mosquitoes].
AB  - The optimal bactoculicide/sphaerolarvicide ratio in combination using against
      Aedes aegypti larvae was established in laboratory by selection. The field trials
      of the selected BS/BT sample containing the ingredients in titer: bactoculicide
      83, sphaerolarvicide-17 were conducted in the arid area of Central Asia. With 1
      g/m2, complete mortality of Culex, Aedes and Anopheles larvae was obtained with
      the residual larvicidal action of 15 days. It is recommended to carry out more
      large-scale trials of the preparation against Anopheles larvae in different
      regions.

PMID- 1354837
TI  - [A comparative evaluation of the activity of pyrethroid-based insecticidal
      preparations].
AB  - A comparative analysis of the results of experimental trials of 12 new effective
      insecticide agents synthesized in the USSR and abroad, containing permethrin,
      deltamethrin, cypermethrin, cyfenothrin, etophenprox and neopinamine as active
      ingredients, against flies, mosquitos, fleas, bedbugs and cockroaches was made.
      The LD50 data in microgrammes per g and millilitres per litre and the LC50 data
      in grammes per sq m are given. All the tested preparations are allowed to use in
      medical desinsection practice.

PMID- 1354839
TI  - The acu-1 gene of Coprinus cinereus is a regulatory gene required for induction
      of acetate utilisation enzymes.
AB  - We have isolated a gene from Coprinus cinereus which cross-hybridises to the facA
      and acu-5 genes of Aspergillus nidulans and Neurospora crassa, respectively.
      These genes encode acetyl-CoA synthetase, an enzyme which is inducible by acetate
      and required for growth on acetate as sole carbon source. We have designated the
      C. cinereus gene acs-1 and have used transformation to demonstrate its functional
      homology to the ascomycete genes by complementation of an N. crassa acu-5
      mutation. The acs-1 gene has never been identified by mutation; mutations leading
      to loss of acetyl-CoA synthetase function map to another gene, acu-1. Using
      Northern analyses we have shown that acu-1 has a regulatory function that is
      required for acetate-induced transcription of acs-1 and of another acetate
      utilisation gene, acu-7, the isocitrate lyase structural gene.

PMID- 1354838
TI  - Positive and negative cis-regulatory elements in the bithoraxoid region of the
      Drosophila Ultrabithorax gene.
AB  - The Ultrabithorax (Ubx) gene is required during embryogenesis and larval
      development to specify the third thoracic and first abdominal segments of
      Drosophila melanogaster. Mutations in the bithoraxoid (bxd) region, a 40 kb DNA
      stretch upstream of the Ubx promoter, affect cis-regulatory elements responsible
      for the ectodermal expression of the Ubx gene in the posterior compartment of the
      third thoracic segment and anterior compartment of the first abdominal segment.
      Our genetic data and the available molecular information are used to map the
      adult epidermal cis-regulatory elements within the bxd region. Genetic
      combinations involving mutations affecting the bxd region show that (1) redundant
      or cooperatively acting sequences are required for Ubx gene expression in the
      anterior compartment of the first abdominal segment, and (2) the expression of
      Ubx in the posterior compartment of the third thoracic segment is modulated by
      positive and negative cis-regulatory elements.

PMID- 1354840
TI  - Human glucokinase gene: isolation, structural characterization, and
      identification of a microsatellite repeat polymorphism.
AB  - The gene encoding human glucokinase (ATP:D-hexose 6-phosphotransferase, EC
      2.7.1.1), a major component of glucose sensing in pancreatic islet beta-cells,
      was isolated and characterized. The gene was shown by Southern blotting to exist
      as a single copy in the genome which mapped to chromosome 7p. It contained 12
      exons including two tissue-specific first exons, one active in islet beta-cells
      (1B), and the other active in liver (1H), and one optional cassette exon which
      was expressed as a minor form in the liver. Thus the three previously reported
      isoforms of glucokinase mRNA were the result of tissue-specific activation of
      separate liver and islet promoters and subsequent alternative splicing events.
      Eleven exons, including 1H and the optional cassette exon 2A, were scattered over
      16 kilobase (kb) in the genome, while exon 1B was separated from the rest by at
      least 20 kb. Although the islet promoter was found to lack a TATA box, a major
      transcript from the islet promoter was mapped 486 nucleotides upstream of the
      translation initiation site. The presence in the islet glucokinase promoter of
      the potential control element GCCACCAG, a homology of the regulatory element
      present in both human insulin (GCCACCGG) and rat insulin (GCCATCTG) genes,
      implied a possible tissue-specific regulatory role of this element. The liver
      promoter was found to contain a TATA box-like sequence, and transcription was
      initiated predominantly at 168 nucleotides upstream of the translation initiation
      site of the major isoform. A new highly polymorphic microsatellite, composed of a
      compound imperfect dinucleotide repeat [GT]15[GA]8CA[GA]7CA[GA]3AA[GA]2, was
      mapped 6 kb upstream of islet exon 1. A polymerase chain reaction-based assay was
      developed, and seven different sized alleles were identified in American Blacks.
      The sequence information reported here, along with the new polymorphic marker,
      will make it possible to clarify the molecular basis of potential glucokinase
      defects in noninsulin-dependent diabetes mellitus patients and may further
      elucidate the nature of genetic susceptibility to the development of this common
      metabolic disease.

PMID- 1354841
TI  - Heterologous desensitization of the human dopamine D1 receptor in Y1 adrenal
      cells and in a desensitization-resistant Y1 mutant.
AB  - In previous studies, mutant clones (designated Y1DR) were isolated that resisted
      ACTH-induced homologous desensitization of adenylyl cyclase. The Y1DR mutation
      also conferred resistance to the homologous desensitization induced by agonist
      stimulation of transfected beta 2-adrenergic receptors. These observations
      suggested that ACTH and beta 2-adrenergic agonists homologously desensitized
      adenylyl cyclase in Y1 cells by a common mechanism. In the present study,
      parental Y1 cells (Y1DS) and the Y1DR mutant were transfected with the gene
      encoding the human dopamine D1 receptor and examined for regulation of adenylyl
      cyclase by dopaminergic agonists. Transformants were isolated from both cell
      lines and shown to respond to dopamine agonists with increases in adenylyl
      cyclase activity. Treatment of the Y1DS transformants with ACTH promoted a rapid,
      homologous desensitization of adenylyl cyclase and had little effect on the
      responses to dopamine or NaF; treatment of Y1DS with dopaminergic agonists
      promoted a slower rate of heterologous desensitization that diminished
      responsiveness of the adenylyl cyclase system to dopamine, ACTH, and NaF. Y1DR
      cells transfected with the dopamine D1 receptor were resistant to the
      heterologous desensitization of adenylyl cyclase induced by dopaminergic
      agonists. These latter observations suggest that the pathways of homologous
      desensitization and heterologous desensitization converge at a common point in
      the desensitization pathway defined by the DR mutation in Y1 cells.

PMID- 1354842
TI  - Comparison of glutamine synthetases from brains of genetically epilepsy prone and
      genetically epilepsy resistant rats.
AB  - Since glutamine synthetase (GS) has been proposed as the primary enzyme in the
      regulation of glutamate metabolism in the central nervous system and since
      inhibition of the activity of this enzyme in vivo leads to seizures, it has been
      proposed that an abnormality in the structure or function of this enzyme could be
      responsible for the induction of seizures in epilepsy prone rats. To test this
      hypothesis the glutamine synthetases were purified from the brains of both
      genetically epilepsy prone rats (GEPR) and their progenitors, genetically
      epilepsy resistant rats (GERR). The enzymes were compared using both SDS-PAGE and
      isoelectric focusing. The immunoreactivities of equal amounts of protein were
      determined using the ELISA technique, and the regulation of the glutamine
      synthetase activities by Mn2+/Mg2+ ratios were compared. The only difference
      found between the glutamine synthetases from the two strains was a slightly lower
      specific activity of the enzyme from the epilepsy prone animals.

PMID- 1354843
TI  - Alpha-methyl-para-tyrosine pretreatment protects from striatal neuronal death
      induced by four-vessel occlusion in the rat.
AB  - Rats were treated with alpha-methyl-para-tyrosine (AMT, 250 mg/kg, i.p), an
      hydroxylase inhibitor, in order to decrease brain levels of catecholamines. Six
      hours later, when cerebral dopamine (DA) and norepinephrine were reduced by about
      80%, a transient forebrain ischemia of 30 min duration was induced by four-vessel
      occlusion technique. Evaluation of brain damage 72 hours after ischemia showed
      that AMT treatment significantly decreased neuronal necrosis in the striatum but
      had no cytoprotective effect in the CA1 sector of the hippocampus and in the
      neocortex. AMT treatment reduced mortality within the ischemic period but did not
      affect either the mortality within the recirculation period or the postischemic
      neurologic deficit. These results suggest that the striatal cytoprotective effect
      of AMT is linked to cerebral DA depletion and that excessive release of DA during
      ischemia or dopaminergic hyperactivity during recirculation play a detrimental
      role in the development of ischemic cell damage in the striatum.

PMID- 1354844
TI  - [The usefulness of dietetic supplementation in feeding after gastric and
      pancreatic surgeries].
AB  - We evaluated the efficacy of an oral artificial supplementation in 22 patients
      who underwent surgery for gastric or pancreatic cancer. From 8th to 14th
      postoperative day, 11 patients (cases) received a diet consistent in their REE,
      and an oral integrator (40% of REE); controls received only the diet. On 7th and
      15th day, nutritional and anthropometric parameters were evaluated, and
      bioelectrical impedance analysis (BIA) was performed to assess body composition.
      The dietary caloric input was similar in cases (1154 kcal, 86.0% of REE) and
      controls (1393 kcal, 92.3% of REE). Due to the integrator, cases reached 121.4%
      of REE (p less than 0.001). The nutritional and anthropometric parameters studied
      did not show significant variations in the two groups, but BIA showed a decrease
      of fat mass in controls with respect to cases (p less than 0.02). Our results
      demonstrate that the oral artificial supplementation was well tolerated, and did
      not reduce food intake, but induced a significant increase of total caloric
      input.

PMID- 1354845
TI  - Measuring the neuromodulatory effects of drugs in man with positron emission
      tomography.
AB  - Cognitive activation in conjunction with pharmacological challenge was used to
      demonstrate neuromodulation in man. Using positron emission tomography (PET),
      measurements of regional cerebral blood flow were made during the performance of
      memory tasks, before and after the administration of apomorphine (dopamine
      agonist), buspirone (5-HT1A partial agonist) or placebo. Drug effects on memory
      induced increases in regional cerebral blood flow were assessed, on a voxel-by
      voxel basis, using statistical parametric mapping. Increases of regional cerebral
      blood flow in response to the memory challenge were attenuated by apomorphine in
      the dorsolateral prefrontal cortex and augmented in the retrosplenial region of
      the posterior cingulate. Conversely, buspirone attenuated blood flow increases in
      the retrosplenial region. These interactions between drugs and a cognitive
      challenge can best be interpreted as neuromodulatory effects.

PMID- 1354846
TI  - Differential effects of in vivo estrogen administration on hypothalamic growth
      hormone releasing hormone and somatostatin gene expression.
AB  - The aim of this study was to investigate the effect of in vivo estrogen
      administration on hypothalamic growth hormone releasing hormone (GHRH) and
      somatostatin (SS) gene expression. We found that estrogen administration
      (estradiol valerate 250 micrograms/every 3 days, subcutaneously) to male rats
      induced a decrease in both hypothalamic GHRH mRNA levels and GHRH content, that
      was significant after 3 and 8 days of treatment. In contrast SS mRNA levels were
      transiently elevated after 1 and 3 days of estrogen administration, returning to
      normal values after 8 days of treatment. These data suggest that the existence of
      sexual dimorphism in GH secretion in the rat could be mediated to some extent by
      gonadal hormones regulating somatostatin and GHRH gene expression in the
      hypothalamus.

PMID- 1354847
TI  - Developmental changes in enzymatic systems involved in protection against
      peroxidation in isolated rat brain microvessels.
AB  - Activities of 3 enzymes involved in the major detoxification pathway for
      peroxides were assessed in rat brain microvessels. Between the 7th and 60th day
      after birth, glutathione peroxidase specific activity remained constant in
      microvessels, while glutathione reductase specific activity increased from day 14
      to day 60. On the other hand, the specific activity of these two enzymes evolved
      similarly in total brain homogenate: they increased between day 7 and day 30, and
      then reached a plateau. In contrast, catalase specific activity in microvessels
      was markedly decreased from day 7 to day 60. A significant decrease in this
      enzyme specific activity was also observed in brain homogenate during
      development. However, in microvessels, catalase specific activity remained higher
      than that of brain homogenate throughout the time period studied. Our results
      support the idea that enzymatic mechanisms against peroxidative damage are
      required in early age, and could be potent at the level of the blood-brain
      barrier.

PMID- 1354848
TI  - Regional variation of excitatory and inhibitory amino acid-induced responses in
      rat dissociated CNS neurons.
AB  - Regional differences in glutamate (Glu), aspartate (Asp), gamma-aminobutyric acid
      (GABA) and glycine (Gly) responses in CNS neurons were investigated by means of
      the whole-cell mode of the patch-clamp technique. The neurons were freshly
      dissociated from rat cortex, limbic system (hippocampal CA1 region), diencephalon
      (ventromedial hypothalamus), medulla (nucleus paragigantocellularis lateralis)
      and spinal cord (spinal dorsal horn). The current amplitudes induced by Glu and
      GABA did not show any regional differences whereas those of Asp- and Gly-induced
      responses were significantly different among CNS regions. The enhancement of Asp
      response by Gly was observed in all regions, and the facilitatory ratio did not
      differ among these regions. Even though the NMDA response in cortical neurons was
      significantly greater than that in spinal neurons, the ratios of NMDA response
      facilitation by Gly were also the same in both regions. When the current
      amplitudes induced by individual amino acids were estimated for the unit surface
      area of respective neurons (current density), the Glu, Asp and Gly responses
      showed regional heterogeneity whereas the GABA response did not.

PMID- 1354849
TI  - Congenital ectopic vas deferens with hypospadias.
AB  - A case of an ectopic vas deferens of an undescended testis is presented which was
      associated with hypospadias. These abnormalities came to light because of the
      systematic approach we have adopted for the investigation of hypospadias in our
      hospital.

PMID- 1354850
TI  - My opinion: NPs and PAs should work together.

PMID- 1354851
TI  - Efficient isolation and mapping of rad genes of the fungus Coprinus cinereus
      using chromosome-specific libraries.
AB  - We have constructed cosmid libraries from electrophoretically separated
      chromosomes of the basidiomycete Coprinus cinereus. These libraries greatly
      facilitate the isolation of genes by complementation of mutant phenotypes and are
      particularly useful for map-based cloning strategies. From a library constructed
      from two co-migrating C.cinereus chromosomes, we isolated a clone that
      complements the C.cinereus rad9-1 mutation. Examination of this clone showed that
      it complements both the repair and meiotic defects of this mutant. Restriction
      fragment length polymorphism mapping using a portion of this clone showed that it
      maps to the rad9 locus. In addition, a single copy of transforming DNA is
      sufficient to complement the rad9-1 defects. Thus, we believe we have cloned the
      rad9 gene itself. We also used a chromosome-specific library and backcrossed
      isolates to rapidly identify a cosmid clone which is tightly linked to the rad11
      locus and is therefore a suitable starting point for a chromosome walk. These
      rapid methods of gene mapping and isolation should be applicable to any organism
      with separable chromosomes.

PMID- 1354852
TI  - cDNA cloning of a novel heterogeneous nuclear ribonucleoprotein gene homologue in
      Caenorhabditis elegans using hamster prion protein cDNA as a hybridization probe.
AB  - The mammalian prion protein (PrPc) is a cellular protein of unknown function, an
      altered isoform of which (PrPsc) is a component of the infectious particle
      (prion) thought to be responsible for spongiform encephalopathies in humans and
      animals. The evolutionary conservation of the PrP gene has been reported in the
      genomes of many vertebrates as well as certain invertebrates. In the genome of
      nematode Caenorhabditis elegans, the sequence capable of hybridizing with the
      mammalian PrP cDNA probe has been demonstrated, predicting the presence of the
      PrP gene homologue in C.elegans. In this study, Southern analysis with the
      hamster PrP cDNA (HaPrP) probe confirmed the previous observation. Moreover,
      Northern analysis revealed that the sequence is actively transcribed in adult
      worms. Thus, we screened C.elegans cDNA libraries with the HaPrP probe and
      isolated a cDNA that hybridizes to the same sequence in C.elegans that hybridized
      with the HaPrP probe in the Southern and Northern analyses. The deduced amino
      acid sequence of this cDNA, however, is substantially homologous with
      heterogeneous nuclear ribonucleoprotein (hnRNP) core proteins rather than
      mammalian PrPc. The hnRNPs contain the glycine-rich domain in the C-terminal half
      of the molecule, which also seemed to be in PrPc at the N-terminal half of the
      molecule. Both of the glycine-rich domains are composed of tracts with high G + C
      content, indicating that these tracts may due to the hybridizing signals. These
      results suggest that this cDNA clone is derived from a novel hnRNP gene homologue
      in C.elegans but not from a predicted PrP gene homologue.

PMID- 1354853
TI  - Identification of the abdominal-A homologue from Aedes aegypti and structural
      comparisons among related genes.

PMID- 1354854
TI  - Calf thymus RF-C as an essential component for DNA polymerase delta and epsilon
      holoenzymes function.
AB  - By using a complementation assay that enabled DNA polymerase delta and DNA
      polymerase epsilon to replicate a singly-DNA primed M13 DNA in the presence of
      proliferating cell nuclear antigen (PCNA) and Escherichia coli single-stranded
      DNA binding protein (SSB), we have purified from calf thymus in a five step
      procedure a multipolypeptide complex with molecular masses of polypeptides of
      155, 70, 60, 58, 39 (doublet), 38 (doublet) and 36 kDa. The protein is very
      likely replication factor C (Tsurimoto, T. and Stillman, B. (1989) Mol. Cell.
      Biol. 9, 609-619). This conclusion is based on biochemical and physicochemical
      data and the finding that it contains a DNA stimulated ATPase which is under
      certain conditions stimulated by PCNA. Together RF-C, PCNA and ATP convert DNA
      polymerases delta and epsilon to holoenzyme forms, which were able to replicate
      efficiently SSB-covered singly-DNA primed M13 DNA. Calf thymus RF-C could form a
      primer recognition complex on a 3'-OH primer terminus in the presence of calf
      thymus PCNA and ATP. Holoenzyme complexes of DNA polymerase delta and epsilon
      could be isolated suggesting that these enzymes directly interact with the
      auxiliary proteins in a similar way. Under optimal replication conditions on
      singly-DNA primed M13 DNA the DNA synthesis rate of DNA polymerase delta was
      higher than of DNA polymerase epsilon. Based on these functional date possible
      roles of these two DNA polymerases in eukaryotic DNA replication are discussed.

PMID- 1354855
TI  - Structure of the gene encoding hepatocyte nuclear factor 1 (HNF1).
AB  - Genomic clones have been isolated that cover the entire gene for the
      transcription factor HNF1 (hepatocyte nuclear factor 1). This protein governs the
      expression of many genes, synthesized in the liver in a tissue-specific manner.
      We have determined the intron/exon structure of the HNF1 gene, which is strictly
      conserved between rat and mouse and estimate that it spans not more than 40kb in
      the rat genome. Whereas most homeoprotein genes do not contain introns within the
      homeodomain, HNF1 displays an intron between the regions encoding the second and
      the third helices. We discuss possible evolutionary mechanisms leading to this
      homeobox intron/exon pattern.

PMID- 1354856
TI  - Variable inhibition of cell-free translation by HIV-1 transcript leader
      sequences.
AB  - The 5' ends of all human immunodeficiency virus type I (HIV-1) transcripts have
      the potential to coordinately regulate translation of HIV-1 mRNAs. Conflicting
      observations of the translational impact of these sequences in various systems
      stimulated these analyses of translation in reticulocyte lysates. We report a
      sensitive, rapid, quantitative, and inexpensive cell-free translation assay in
      which translational efficiency is monitored by enzymatic assay of the translation
      products. Using this assay and conventional radiolabeling assays, we demonstrate
      that the HIV-1 transcript leader inhibits downstream translation and that the
      stem-loop structure is required. Under our assay conditions, this inhibition
      occurs predominantly in cis and is not mediated by the 68 kD, interferon-induced,
      double-stranded RNA-activated kinase (p68). However, under other assay conditions
      the HIV-1 leader may activate p68 and inhibit translation in trans. We show that
      variation between individual preparations of cell-free extracts can dramatically
      alter the magnitude of the translational inhibition by the HIV-1 leader. Further,
      we provide evidence that a heat-labile factor is required for efficient
      translation of transcripts containing the HIV-1 leader. These observations
      provide a foundation for identifying factors required for translation of HIV-1
      transcripts.

PMID- 1354857
TI  - Control of intestinal motility by different receptor systems.

PMID- 1354858
TI  - Genomic aspects of drug-induced xenogenization of murine tumors.

PMID- 1354859
TI  - Pharmacological modulation of development and plasticity in nigro striatal
      dopaminergic neurons.

PMID- 1354860
TI  - A comparative study of B-HT 920 and diazepam in the X-maze feeding test.

PMID- 1354862
TI  - Biochemical and functional identification of dopamine receptors in rat brown
      adipose tissue.

PMID- 1354861
TI  - Niaprazine vs chlordesmethyldiazepam in sleep disturbances in pediatric
      outpatients.

PMID- 1354863
TI  - GABA and glutamate receptors as therapeutic targets in neurodegenerative
      disorders.

PMID- 1354864
TI  - Alpha- and beta-adrenoceptors in hypertension: molecular biology and
      pharmacological studies.
AB  - Recent years have witnessed astonishing progress in our understanding of the
      molecular basis of adrenoceptor structure, function and regulation and revealed
      an unexpected heterogeneity of adrenoceptors demonstrating the existence of at
      least 11 subtypes. This paper discusses the implications of these advances on
      studies regarding a specific role of adrenoceptors in the development of genetic
      hypertension. The available data indicate that among the alpha-adrenoceptor
      subtypes the alpha 2A-adrenoceptor is the most likely candidate for an alteration
      specifically linked to genetic hypertension in the animal model of the
      spontaneously hypertensive rat and possibly in some patients. Alterations of
      other alpha-adrenoceptor subtypes may be specific for some forms of genetic
      hypertension but are unlikely to play an important role for blood pressure
      regulation. Most beta-adrenoceptor alterations appear to occur secondary to blood
      pressure elevation independently of whether hypertension has occurred on a
      genetic basis or not. Moreover, the mechanisms regulating alpha- and beta
      adrenoceptor responsiveness upon prolonged agonist exposure may be altered in
      hypertension and thereby contribute to the pathophysiology of this disease.

PMID- 1354865
TI  - Serotonergic receptors and drugs in hypertension.
AB  - The possible role of 5-hydroxytryptamine (5HT) and 5HT-receptors in hypertension,
      already suggested by Page in 1954, has been subject to a renaissance of interest
      owing to the development of antihypertensive drugs which interact with 5HT
      receptors. These drugs, like ketanserin, urapidil and flesinoxan are used as
      tools to study the role of 5HT and its receptors in hypertension. Some arguments
      would plead in favour of a certain role of 5HT and 5HT-receptors in the
      pathogenesis and maintenance of hypertension: hyperresponsiveness of blood
      vessels from hypertensive patients and animals to 5HT-induced constriction; the
      antihypertensive/vasodilator activity of the 5HT2-receptor antagonist ketanserin;
      enhanced sensitivity of platelets from hypertensives to 5HT. However, there are
      also several arguments which do not support a causal role of 5HT in hypertensive
      disease: 5HT is not a generally accepted pressor agent, whereas its concentration
      in the circulating blood is subthreshold; the 5HT2-receptor antagonist ketanserin
      is the only agent of this type which lowers blood pressure, other 5HT2-receptor
      blockers (ritanserin; LY 53587) being inactive. The various data and arguments
      available do not unequivocally support a relevant role of peripheral 5HT and its
      receptors in hypertensive disease. 5HT2-receptor blockade may, however, have a
      favourable effect on the microcirculation under pathological conditions. The
      stimulation of central 5HT1A-receptors by drugs like urapidil, 8-OH-DPAT or
      flesinoxan, has been demonstrated to induce peripheral sympathoinhibition and a
      fall in blood pressure. This mechanism appears to be a novel target for centrally
      acting antihypertensives, clearly different from that of clonidine and related
      drugs, which are centrally acting alpha 2-adrenoceptor agonists.

PMID- 1354867
TI  - [Macrocarcinoidosis of the stomach in a MEN 1 patient with Zollinger-Ellison
      syndrome and hyperparathyroidism].

PMID- 1354866
TI  - Five years' experience of prenatal diagnosis of cystic fibrosis in the former
      U.S.S.R.
AB  - From a total of 490 cystic fibrosis (CF) high-risk families under supervision
      (mostly Russian Slavs from the European part of the country), DNA data including
      both direct screening for some CF gene (CFTR) mutations (delF508, G551D and
      1677delTA) and allelic polymorphism studies with tightly CF linked DNA markers
      were collected from 261 families. All full families (129) and 86 CF families with
      a decreased index child were found to be either fully (42 per cent) or partially
      (40 per cent) informative for DNA analysis. Prenatal diagnosis (PD) was carried
      out in 161 CF families. Microvillar enzyme (MVE) assay was applied to all 140 PD
      at the second trimester either as a single test (88) or in conjunction with DNA
      analysis (52). The frequency of false-negative results of the MVE assay was 1.3
      per cent and that of false-positive results, as judged by the albumin meconium
      test, was 5.0 per cent. Ambiguous results of MVE analysis were found in 30 cases,
      12 of which were verified by DNA analysis. Molecular diagnosis of CF at the first
      trimester was carried out in 21 cases and four pregnancies were terminated.
      Altogether, 39 pregnancies with a predicted high risk of CF fetuses were
      terminated. The low average frequency of delF508 in CF chromosomes of Russian
      Slavs (50 per cent), its remarkable inter-population variation, and the
      significant proportion of at-risk families without an affected child determine
      the necessity of combined molecular and biochemical (MVE assay) approaches for
      efficient prenatal diagnosis of CF in the former U.S.S.R.

PMID- 1354868
TI  - [Supraselective vagotomy. Long-term results in the treatment of duodenal ulcer].

PMID- 1354869
TI  - [Drug resistance genes].
AB  - Among the different mechanisms of multidrug resistance, the overexpression of the
      mdr1 gene has been actively investigated during the last 5 years. This gene
      encodes a 170 kDa protein, named P-gp, a member of a transporter superfamily, the
      ABC (ATP Binding Cassette) proteins. P-gp actively expels out of the tumoral cell
      different drugs like anthracyclins, vinca alkaloids, epipodophyllotoxins. The
      involvement of mdr1 gene in clinical drug resistance is now demonstrated, and
      several trials using P-gp modulators and chemotherapy are going on in resisting
      tumors. Other intrinsic drug resistance mechanisms, such as increase of
      intracellular glutathione content or decrease of topoisomerase activity, could be
      involved in clinical drug resistance.

PMID- 1354870
TI  - Pathobiology of the Dentin/Pulp Complex. International conference. Charlotte,
      North Carolina, May 25-29, 1991.

PMID- 1354871
TI  - Root resorption following traumatic dental injuries.
AB  - Permanent teeth are usually not attacked by osteoclasts despite their situation
      in a site where active bone resorption constantly takes place as a result of
      local and systemic osteoclast activating factors. This fact points to
      antiresorption factors residing in both the periodontal ligament (PDL) and the
      pulp. Concerning the PDL homeostasis factor (i.e. permanency of a separation
      between the alveolar socket and the root surface and protection of the root
      surface against osteoclastic activity), recent studies have shown that this
      factor, at least with respect to trauma and wound healing, is linked to, and
      probably resides in, the cementoblast layer and/or the cells next to this layer.
      If there is loss of this tissue integrity, root resorption may occur; especially
      if non-PDL derived cells gain access to the site. With respect to the pulp, no
      systematic research has been performed regarding the homeostasis of this
      structure (i.e. permanency of the pulpal organ with its specific anatomy and
      functional stability). In evaluating the events where resorption does occur, it
      appears that the loss of tissue components within the pulp (including
      odontoblasts) implies a risk of root canal resorption if nonpulpally derived
      cells gain access to the site. Root resorption following traumatic dental
      injuries, whether located along the root surface or within the root canal appears
      to be a sequel to wound healing events, where a significant amount of the PDL or
      pulp has been lost due to the effect of acute trauma. The goal of these processes
      is removal of injured tissue from zones of trauma, space creation for
      neovascularization or control of infection. Irrespective of the goal, these
      processes have a potential for root resorption. The type of tissue repair, i.e.
      repair originating from the dental pulp, the PDL or bone or a combination, seems
      to be of importance in determining the risk of root resorption during the healing
      process.

PMID- 1354872
TI  - Regulation of tumor necrosis factor receptors on phagocytes.

PMID- 1354873
TI  - Response of blood serum constituents to production of and recovery from a
      kwashiorkor-like syndrome in the young pig.
AB  - Twenty-six 3-week-old genetically obese pigs were fed in two experiments to
      determine the serum chemistry profile during severe protein malnutrition and
      repletion. Severe protein deficiency was produced in pigs fed the high-fat, low
      protein diet (growth failure, rough hair, low serum total protein and albumin).
      In Experiment 1, blood was sampled from the anterior vena cava of each pig five
      times during depletion and three times during repletion to determine serum total
      cholesterol, high density lipoprotein (HDL)-cholesterol, triglycerides, total
      protein, albumin, glucose, Ca, inorganic P, Mg, Na, K, Cl, total bilirubin, urea
      N, creatinine, alkaline phosphatase, alanine aminotransferase, aspartate
      aminotransferase, and gamma-glutamyltransferase. In Experiment 2, blood was
      sampled weekly for 8 weeks for serum total cholesterol, HDL-cholesterol,
      triglycerides, albumin, glucose, Ca, P, Mg and alkaline phosphatase. HDL
      cholesterol was increased (P less than 0.01) and albumin was decreased (P less
      than 0.01) in protein-deficient pigs in both experiments. Creatinine, total
      bilirubin, gamma-glutamyltransferase, alanine aminotransferase, and aspartate
      aminotransferase were elevated in protein-deficient pigs compared with controls
      after 7 weeks of depletion. Inorganic P (P less than 0.01), Ca (P less than
      0.01), and Mg (P less than 0.05) concentrations were depressed in protein
      depleted pigs compared with controls in both experiments. After 8 weeks of
      repletion in Experiment 1, all elements except inorganic P were similar in the
      two groups. Short-term, severe, protein malnutrition affected lipid, electrolyte,
      and structural mineral metabolism and indices of liver function in the absence of
      parasites, diarrhea, and infection. The effects were reversed after 8 weeks of
      repletion. We conclude that the elevated serum cholesterol in protein deficiency
      is related primarily to an increase in the HDL fraction.

PMID- 1354874
TI  - Cardioprotective effects of the vasodilator/beta-adrenoceptor blocker,
      carvedilol, in two models of myocardial infarction in the rat.
AB  - The purpose of this study was to evaluate the cardioprotective effects of
      carvedilol, a beta-adrenergic blocker and vasodilator, in two models of ischemic
      myocardial damage in the rat. Following coronary artery occlusion for 0.5 h and
      reperfusion for 24 h (MI/R group), left ventricular (LV) injury was determined by
      planimetric analysis of triphenyltetrazolium chloride-stained tissue, and
      polymorphonuclear leukocyte infiltration was assessed by measuring
      myeloperoxidase (MPO) activity. In the vehicle-treated MI/R group, infarct size
      was 14.2 +/- 1.3% of the LV (n = 16), and MPO activity was increased to 2.8 +/-
      0.7 from 0.14 +/- 0.03 U/g tissue in the vehicle-treated sham-occluded group (p
      less than 0.01). Carvedilol (1 mg/kg i.v., 15 min prior to coronary artery
      occlusion and at 3.5 h following reperfusion) reduced myocardial infarct size to
      7.5 +/- 1.2% of the LV (n = 14; p less than 0.01) and attenuated the increase in
      MPO activity to 1.4 +/- 0.4 U/g tissue (p less than 0.05). A lower dose of
      carvedilol (i.e. 0.3 mg/kg i.v.) did not limit myocardial infarct size or the
      increase in MPO activity. In a model of permanent coronary artery occlusion, 24
      hour survival was reduced from 85% in sham-occluded animals (n = 38) to 44% in
      the vehicle-treated MI group (n = 84; p less than 0.01). In comparison to the
      vehicle-treated MI group, carvedilol (0.3 mg/kg i.v., 15 min prior to coronary
      artery occlusion and 1 mg/kg 4 h after occlusion) improved survival by 55% (n =
      64; p less than 0.05, compared to the vehicle-treated MI group), whereas the same
      dose of propranolol (n = 42) had no significant effect on survival. These results
      indicate that carvedilol reduces myocardial ischemia/reperfusion injury, and
      significantly improves survival in a permanent coronary artery occlusion model of
      myocardial infarction.

PMID- 1354875
TI  - Effect of pinacidil on spontaneous and evoked contractile activity.
AB  - Uninhibited bladder contractions have been associated with a variety of bladder
      dysfunctions including outlet obstruction, neurogenic bladder, incontinence, and
      other neurologic and nonneurogenic bladder disorders. One class of compounds that
      is gaining popularity and support for the treatment of hyperreflexia is potassium
      channel openers, such as pinacidil and cromakalim. In general, these agents act
      by hyperpolarizing the smooth muscle membrane, resulting in an increase in
      membrane stability which in turn would be expected to inhibit spontaneous and
      evoked contraction. It is the purpose of this study to compare the potency and
      selectivity of pinacidil at inhibiting both hyperreflexia in vivo, and several
      forms of in vitro contractile stimulation in the rabbit. The following is a
      summary of the results. (1) Pinacidil is an effective inhibitor of hyperreflexia
      in the in vivo rabbit model. (2) Pinacidil is a substantially more potent
      inhibitor of the amplitude of the hyperreflexia than the frequency. (3) Pinacidil
      was substantially more potent at inhibiting the contractile response to 2-Hz
      stimulation than to 32-Hz stimulation, but was equally effective at inhibiting
      field stimulation of the bladder base and body. (4) Pinacidil was significantly
      more potent at inhibiting the peak response to field stimulation than the rate of
      tension generation. (5) Pinacidil was equally potent and effective at inhibiting
      the phasic and tonic components of the response to field stimulation. (6)
      Pinacidil was a more potent inhibitor of methoxamine stimulation of the bladder
      base than bethanechol stimulation of the bladder body. (7) Pinacidil was a
      noncompetitive or mixed inhibitor of both methoxamine and bethanechol
      stimulation, whereas it was a competitive inhibitor of KCl stimulation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1354876
TI  - Receptor protection studies with phenoxybenzamine indicate that a single alpha 1
      adrenoceptor may be coupled to two signal transduction processes in vascular
      smooth muscle.
AB  - Full alpha 1-adrenoceptor agonists, such as (-)-norepinephrine, produce
      vasoconstriction in the rat aorta primarily through the mobilization of
      intracellular stores of calcium, whereas partial alpha 1-adrenoceptor agonists,
      such as (-)-dobutamine, produce vasoconstriction primarily through the
      translocation of extracellular calcium. The different pools of calcium utilized
      by full and partial alpha 1-adrenoceptor agonists have been proposed to result
      from the activation of different alpha 1-adrenoceptor subtypes. The irreversible
      alpha 1-adrenoceptor antagonist, phenoxybenzamine, selectively eliminates only
      that component of an alpha 1-adrenoceptor-mediated response in the rat aorta that
      is dependent upon the mobilization of intracellular stores of calcium. In order
      to determine whether in the rat aorta there exist two distinct alpha 1
      adrenoceptor subtypes linked separately to the mobilization of intracellular and
      extracellular calcium, we utilized the full and partial alpha 1-adrenoceptor
      agonists, (-)-norepinephrine and (-)-dobutamine, respectively, and the
      irreversible antagonist, phenoxy-benzamine, as pharmacologic tools in a classical
      receptor-protection study to probe these alpha 1-adrenoceptor-mediated
      vasoconstrictor process(es). Our logic was that if the intracellular and
      extracellular pools of calcium were coupled to different alpha 1-adrenoceptor
      subtypes, then only (-)-norepinephrine, and not (-)-dobutamine, would protect
      against alpha 1-adrenoceptor alkylation by phenoxybenzamine, since
      phenoxybenzamine only eliminates the process that depends on intracellular
      calcium. Alternatively, if both (-)-norepinephrine and (-)-dobutamine produce a
      similar degree of alpha 1-adrenoceptor protection against phenoxybenzamine, our
      results would suggest that a single alpha 1-adrenoceptor subtype exists which
      activates both the translocation of extracellular calcium and the mobilization of
      intracellular calcium. Phenoxybenzamine (30 nM) abolished contractions of the rat
      aorta produced by (-)-norepinephrine, as expected. Pretreatment of the tissues
      with either (-)-norepinephrine or (-)-dobutamine, at concentrations that produced
      equivalent degrees of alpha 1-adrenoceptor occupancy, resulted in equal
      protection against alkylation of alpha 1-adrenoceptors by phenoxybenzamine,
      arguing against the existence of two distinct alpha 1-adrenoceptor subtypes in
      the rat aorta. These results are consistent with our previous hypothesis that two
      different signal-transduction processes may be activated in the rat aorta by a
      single alpha 1-adrenoceptor population, with the intrinsic efficacy of the
      agonist determining which signal-transduction process is activated.

PMID- 1354877
TI  - Dynorphin receptor changes in hippocampus of the spontaneously hypertensive rat.
AB  - Dynorphin receptor binding sites in hippocampal membrane preparations were
      assessed in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 4, 8,
      12 and 16 weeks of age. At 4 weeks of age, before hypertension is manifested,
      SHRs had significantly more hippocampal dynorphin receptor binding sites than WKY
      controls. At 8, 12 and 16 weeks of age, however, when hypertension is seen, SHRs
      showed significantly fewer hippocampal binding sites than WKY rats. No receptor
      affinity changes for dynorphin were seen between the two strains of rats at any
      age. These results suggest that hippocampal receptor changes involving the opioid
      system may play a role in the central component of blood pressure control.

PMID- 1354878
TI  - [Drug management and therapy resistance. A cross-sectional study of schizophrenic
      patients in a large psychiatric hospital].
AB  - In a cross-sectional study 473 schizophrenic patients of a great psychiatric
      hospital were served. It was looked for differences in patients' characteristics
      and pharmacotherapy according to the therapeutic-functional structure of the
      hospital (admission-Unit, sociotherapeutic and long-time wards). Differences in
      drug-management became evident on basis of a regimen, which applies high doses
      (number of psychotropic drugs, chlorpromacin-units) in general, despite
      recommendations in the literature. The treatment refractory patients in the long
      time wards are found to be heterogeneous and the authors suggest alternative
      pharmacological and psychosocial interventions.

PMID- 1354880
TI  - [Acute dyskinesia as the cause of jaw dislocation].
AB  - A case of an acute dyskinesia of a young, schizophrenic woman caused by
      neuroleptic therapy is reported. The acute dyskinesia was the reason for a
      complete luxation in the jaw-joint. The patient showed phenomenons (brain
      atrophy, cognitive dysfunction, negative symptoms) which are discussed to be
      connected with acute dyskinesia. They also are a danger-signal regarding the
      beginning of a tardive dyskinesia.

PMID- 1354879
TI  - [Neuroleptic malignant syndrome--a case report on diagnosis, differential
      diagnosis and therapy of a life threatening complication of treatment with
      neuroleptics].
AB  - The neuroleptic malignant syndrome is a potentially lethal consequence of
      treatment with neuroleptics. It is possible that a patient, suffering from
      neuroleptic malignant syndrome now, had no such illness in the past, while being
      treated with neuroleptics; furthermore he may respond well to rechallenge with
      the original agent in the future. The malignant neuroleptic syndrome of a 29 year
      old man, whom we treated with benperidole, is described. The course of the
      disease and the differential-diagnosis is stated. The ways of treatment with
      bromocriptine, dantrolene sodium and amantadine, as described in the literature,
      are presented. As the neuroleptic malignant syndrome ist rare many cases should
      be collected in order to enhance the knowledge of the etiology and the
      pathogenesis of that life--threatening complication of treatment with neuroleptic
      drugs.

PMID- 1354881
TI  - [Effect of combined pharmaco- and psychotherapy in schizophrenia ambulatory care
      on rehospitalization incidents and treatment costs].
AB  - For a total of 89 outpatients of a schizophrenia outpatient clinic, the times of
      hospitalization up to 5 years before treatment in this institution, have been
      compared to the frequency of rehospitalization within up to 5 years of
      posthospital care. This treatment contained between 1 1/2 and 2 years neuroleptic
      medication (one half as long-term prophylaxis, the other half as interval
      medication) and psychotherapy in form of single talk of partly in groups for
      patients and their relatives. Thru this, the duration of hospitalization, before
      10 weeks by average per anno, could be reduced to 2.1 weeks yearly. Time
      intensive and multi-dimensional posthospital care able to reduce the duration of
      hospitalizations essentially. This has also a positive influence on the total
      costs of treatment. The positive effect lasts only in part, by the end of
      posthospital care the times of rehospitalization increase slightly, especially by
      repeated sick patients.

PMID- 1354882
TI  - [Quality assurance in the psychiatric hospital--joint medical-pharmaceutical
      visits].
AB  - The authors report on two years of experience collected during jointly performed
      medico-pharmaceutical visits in a psychiatric hospital. From the viewpoint of
      quality assurance and quality control such a procedure has now gained topical
      importance. Attention is drawn to problematic drug regimens and interactions
      between drugs.

PMID- 1354885
TI  - 7th International Symposium of Nephrology at Montecatini. Montecatini-Terme,
      Italy, October 14-16, 1991. Abstracts.

PMID- 1354883
TI  - Attentional fatigue following breast cancer surgery.
AB  - Attentional fatigue usually follows intense use of mental effort and is
      manifested as a decreased capacity to concentrate, that is, to direct attention.
      The purpose of this study was to examine the capacity to direct attention in
      persons with cancer during the initial phase of illness. The sample consisted of
      32 women without cognitive or affective disorders who underwent surgery for
      localized (Stage I or II) breast cancer. Subjects manifested attentional deficits
      of varying intensity on a battery of tests of directed attention on the day
      before discharge from the hospital, which was a mean of 3 days following
      mastectomy or breast conservation surgery. Unexpectedly, the two surgical groups
      did not differ significantly in attentional capacity and functioning. Attentional
      test scores were not significantly correlated with narcotic pain medication
      interval, mood state, or self-ratings of attentional functioning. However, as
      number of days postsurgery increased, attentional performance decreased. The
      theoretical basis for further examination of attentional fatigue in people with
      cancer or other life-threatening illnesses is discussed.

PMID- 1354884
TI  - Factors affecting severity of injury and recovery of function. Proceedings of the
      International Symposium on Acute Renal Failure. Chapel Hill, North Carolina,
      October 2-4, 1991.

PMID- 1354886
TI  - A seroepidemiological survey of antibodies to HTLV-I/HTLV-II in selected
      population groups in Paraguay.
AB  - Between March 1987 and November 1989 a cross-sectional serological survey was
      conducted on 884 residents of Paraguay to obtain data on the prevalence of
      antibodies to human T-cell leukemia virus type I/II (HTLV-I/II). Sera from 8/884
      individuals (0.9%) were positive, confirmed by Western blotting and
      radioimmunoprecipitation (RIPA). This study shows that HTLV-I/II is very rare (or
      absent) among the general (healthy) population (0/338) and ethnic Japanese
      (0/227) in Paraguay. However, it can be detected at a rate of 2-3% in prostitutes
      (4/178) and homosexuals (4/117), suggesting sexual transmission as an important
      route for spread of HTLV-I/II in Paraguay.

PMID- 1354887
TI  - A seroepidemiological study of HTLV-1 infection in Nepal.
AB  - A seroepidemiological survey of antibodies to human T-lymphotropic retrovirus
      type-1 (HTLV-1) was carried out among 413 residents of Chitwan, Dhapakhel and
      Katmandu in Nepal. Donor screening was first carried out by the gelatin particle
      agglutination (PA) tests and positive sera were retested by an improved PA test,
      indirect immunofluorescence (IF) and Western blotting (WB). Nine sera showed
      positive reaction in the first PA screening. Among these positive sera, 1 serum
      was positive in the improved PA test and the IF test but negative in the WB test.
      This study suggests that the prevalence of HTLV-1 in Nepalese people is
      negligible.

PMID- 1354888
TI  - 'Mystery' virus meets the skeptics.

PMID- 1354889
TI  - Maintenance of in vivo tolerance by persistence of antigen.
AB  - T cells of the immune system respond only to foreign antigens because those cells
      with reactivity for self proteins are either deleted during their development or
      rendered nonresponsive (anergic). The maintenance of the nonresponsive state was
      found to require the continual exposure of the anergic T cells to antigen. When
      anergic T cells were removed from the self antigen by adoptive transfer to a
      mouse strain lacking the antigen or by in vitro culture, nonresponsiveness was
      reversed and the anergic cells returned to normal functional status.

PMID- 1354890
TI  - [Testicular autotransplant and laparoscopic orchiectomy in a case of bilateral
      adult cryptorchism].
AB  - B.L. a 27 year old bilaterally cryptorchid patient underwent right testicular
      autotransplantation in the presence of a quite normal testis. After one year the
      patency of microsurgical anastomosis was confirmed by means Doppler flowmetry and
      scrotal echography demonstrated the presence into the scrotum of a testis
      provided of a normal echogenicity. Left laparoscopic orchiectomy was planned. A
      small semilunar skin incision was made just below the rime of the umbilicus.
      Veress needle was introduced: as soon as the needle pierced the parietal
      peritoneum, its spring mechanism was released allowing the sharp needle point to
      retract leaving only the blunt tip protruding. Carbon dioxide gas was insufflated
      through the side part of the Veress needle until adequate abdominal distension
      was achieved. After having removed the Veress needle, the laparoscope on its
      sharp-pointed trocar was introduced into the peritoneal cavity and left testis
      was easily localized. Four trocars were introduced up to proceed to laparoscopic
      orchiectomy. The patient was discharged two days after. In our opinion in the
      presence of a bilateral cryptorchism in the adult, is better to plan a
      monolateral autotransplantation. After having verified the long-term result of
      microsurgery we can decide if a contralateral orchiectomy has to be planned.

PMID- 1354891
TI  - Concomitant chemoradiotherapy for solid tumors: rationale and clinical
      experience. Proceedings of a seminar. Chicago, Illinois, September 26-27, 1991.

PMID- 1354892
TI  - IVIG: Current role in bone marrow transplant, malignancy, and immune hematologic
      disorders. Symposium proceedings. Scottsdale, Arizona, October 10-13, 1990.

PMID- 1354893
TI  - [The current trends in thrombolytic therapy with different indications].

PMID- 1354894
TI  - [The content of gastrin, bombesin and somatostatin in the blood and gastric juice
      of patients with duodenal and gastric peptic ulcer].
AB  - Ninety patients suffering from peptic ulcer and 25 healthy subjects were examined
      for the content of gastrin, bombesin and somatostatin in blood and gastric juice.
      Among patients with duodenal ulcer, 2 groups were distinguished: group I included
      patients in whom peptic ulcer occurred before 30 years; the majority of the
      patients manifested blood hypergastrinemia, a decrease of bombesin concentration
      and normal somatostatin concentration; gastric juice was characterized by a
      lowering of somatostatin concentration and unchanged gastrin concentration; group
      II was made up of patients who developed peptic ulcer after 30: in the majority
      of the patients, gastrin concentration was reduced under basal conditions, after
      loading it was unchanged; in part of the patients, blood somatostatin
      concentration was elevated, in 16 in exacerbation and in 19 in remission; in the
      remainder, it was unchanged. The concentration of bombesin in blood remained
      unchanged. In gastric juice, gastrin concentration was increased only after
      histamine administration, somatostatin concentration was unchanged whatever the
      disease stage. In patients with gastric ulcer, gastrin concentration in blood was
      elevated only under basal conditions, being unchanged in gastric juice
      irrespective of the disease stage. Meanwhile, the concentration of bombesin was
      lowered both under basal conditions and after insulin administration, the
      concentration of somatostatin was decreased both in blood and gastric juice
      whatever the disease stage.

PMID- 1354895
TI  - Neural tube and other developmental anomalies in the guinea pig following
      maternal hyperthermia during early neural tube development.
AB  - Guinea pigs were exposed to hyperthermia for 1 hr once or twice on day 11, 12,
      13, or 14 (E11-E14) of pregnancy. The mean rectal temperatures were elevated by
      3.4 degrees C-4.0 degrees C. This treatment resulted in a marked elevation of
      rates of resorption and developmental defects in embryos examined at day E23. The
      defects observed were those affecting the neural tube (NTD) (exencephaly,
      encephaloceles, and microphthalmia), kyphosis/scoliosis, branchial arch defects,
      and pericardial edema. Embryos with NTD and kyphosis/scoliosis have not been
      found among newborn guinea pigs to date following maternal heat exposure on days
      E12-E14. It appears that embryos with these defects are filtered out by
      resorption or abortion by days E30-E35.

PMID- 1354896
TI  - Modulation of cyclophosphamide mutagenicity by vitamin C in the in vivo rodent
      micronucleus assay.
AB  - The modulatory effect of vitamin C (Vit C) on the mutagenic effect of the
      antineoplastic drug cyclophosphamide (CP) was assessed in the in vivo
      micronucleus test in Swiss mice. Simultaneous oral administration of Vit C with
      i.p. administration of CP was found to decrease the frequency of micronucleated
      polychromatic erythrocytes elevated by CP. Vit C exhibited a significant
      antimutagenic effect over a wide dose range (1.56-200 mg/kg). The dose-response
      relationship was highly significant. These results demonstrated the ability of
      the in vivo micronucleus test to detect in vivo modulation of CP mutagenicity by
      Vit C. Our earlier results and those from other laboratories also indicate that
      this model system is suitable for primary in vivo screening of modulation of
      mutagenesis.

PMID- 1354897
TI  - Tobramycin-induced changes in renal histology of fetal and newborn Sprague-Dawley
      rats.
AB  - Effects on renal development were studied using tobramycin (TBM) as a model
      compound. Pregnant Sprague-Dawley rats were injected i.p. with TBM at 30 or 60
      mg/kg body weight/day on gestational days (GD) 10-19. Kidneys from dams and
      conceptuses were examined on GD 20 and on postnatal day (PD) 9. The dosing
      regimen caused in dams moderate proximal tubular alterations and increased
      concentrations in serum creatinine. Fetal kidneys showed granularity and swelling
      of proximal tubule cells at the 30 mg/kg dose, poor glomerular differentiation at
      the 60 mg/kg dose, increased glomerular density at both doses, and no changes on
      macroscopic examination at either dose. In newborns were observed a moderate
      developmental delay and tubular lesions at the higher dose, and dose-related
      increases of glomerular density and relative medullary area at both doses. All
      findings were more pronounced in males. A maturational disruption of the tubular
      structures possibly leading to increased glomerular density was attributed to TBM
      exposure during renal organogenesis in the rat.

PMID- 1354898
TI  - Evaluation in a battery of in vivo assays of four in vitro genotoxins proved to
      be noncarcinogens in rodents.
AB  - 2-Chlorethanol, 8-hydroxyquinoline, 2,6-toluenediamine, and eugenol, previously
      found to behave as genotoxins in in vitro systems and as noncarcinogens in
      rodents, were evaluated for their ability to induce genotoxic effects in vivo.
      Rats were given by gavage a single or two successive doses equal to one-half the
      corresponding LD50, killed at different times after treatment, and examined for
      the following end points: the frequency of both micronucleated polychromatic
      erythrocytes in the bone marrow and micronucleated hepatocytes (after partial
      hepatectomy); the in vivo-in vitro induction of DNA fragmentation, as measured by
      the alkaline elution technique, and of unscheduled DNA synthesis, as measured by
      autoradiography, in hepatocyte primary cultures. The two latter end points were
      also evaluated after in vitro exposure of hepatocytes to log-spaced subtoxic
      concentrations. 2-Chloroethanol, 8-hydroxyquinoline, and eugenol never produced
      effects indicative of genotoxic activity. The same happened with 2,6
      toluenediamine, with the exception of a significant increase over controls in the
      amounts of DNA damage and repair displayed by hepatocyte cultures obtained from
      rats given two 1/2 LD50 separated by a 24 h interval. Our results, which, apart
      the above mentioned exception, are in concordance with the rodent carcinogenicity
      results, contribute to underline the role of in vivo short-term tests for the
      detection of potential genotoxic carcinogens.

PMID- 1354899
TI  - Diphenylhydantoin is not genotoxic in a battery of short-term cytogenetic assays.
AB  - 5,5-Diphenylhydantoin (DPH) is an antiepileptic drug associated with an increase
      in malformations in infants born to women taking DPH during pregnancy. Positive
      and negative results have been reported by various investigators for in vivo and
      in vitro chromosome aberration (CAB) assays, in vivo and in vitro sister
      chromatid exchange (SCE) assays, and in vivo micronucleus tests (MNT). In this
      laboratory, DPH was tested in an in vitro CAB assay using Chinese hamster ovary
      cells with and without an S-9 activation system, an in vivo SCE assay in female
      CD-1 mice, an in vivo MNT, using both male and female CD-1 mice, and a
      transplacental micronucleus test. The results from this comprehensive battery of
      cytogenetic tests were uniformly negative and support a conclusion that the known
      teratogen, DPH, is not clastogenic.

PMID- 1354900
TI  - Monoclonal antibody-based enzyme-linked immunoassays for the measurement of
      palytoxin in biological samples.
AB  - Mouse monoclonal and rabbit polyclonal antibodies were produced against
      conjugates of keyhole limpet hemocyanin and chemically defined palytoxin haptens.
      Palytoxin haptens were produced by derivatization of the primary amino group with
      sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate or succinimidyl
      3-(2-pyridyldithio)propionate. Selected antibodies were used to develop five
      palytoxin-specific enzyme-linked immunoassay formats for the quantitation of
      palytoxin in biological matrices, including crude extracts of Palythoa
      tuberculosa. The formats developed include an indirect competitive inhibition
      enzyme-linked immunoassay, two types of direct competitive inhibition enzyme
      linked immunoassays, and both indirect and direct sandwich enzyme-linked
      immunosorbent assays. The sandwich enzyme-linked immunosorbent assays are capable
      of detecting as little as 10 pg palytoxin per test, but may be subject to matrix
      interference. The direct competitive inhibition enzyme-linked immunoassays detect
      as little as 30 pg palytoxin per test with a total assay time of only 4 hr. The
      enzyme-linked immunoassays do not cross-react with the other marine toxins
      tested, but do cross-react with certain non-toxic, treated preparations of
      palytoxin. The enzyme-linked immunoassays were used to quantitate palytoxin in P.
      tuberculosa extracts and to monitor toxin isolation. These enzyme-linked
      immunoassay systems can substitute for the mouse bioassay of palytoxin, providing
      a rapid, sensitive, and accurate means of toxin detection.

PMID- 1354901
TI  - Beachside preparation of jellyfish nematocyst tentacles.
AB  - A comparison of methods for preparing a jellyfish nematocyst suspension from sea
      nettle (Chrysaora quinquecirrha) fishing tentacles at the beachside was
      conducted. Autolysis of the tentacle followed by straining and sedimentation on
      ice was found to be a satisfactory technique. This procedure utilized a tea
      strainer, plastic cup and conical centrifuge tube, all of which could be made
      available at a minimally equipped laboratory.

PMID- 1354902
TI  - Cardiac alpha 1-adrenoceptors mediate positive inotropy via myofibrillar
      sensitization.

PMID- 1354903
TI  - Pharmacological prospects for alpha 2-adrenoceptor antagonist therapy.
AB  - The discovery of various alpha 2-adrenoceptor subtypes in numerous tissues and
      studies of alpha 2-adrenoceptor-mediated mechanisms has generated considerable
      interest in their physiological functions. It has also increased possibilities
      for the design of new pharmacological tools and for the study of the
      pharmacological impact of new drugs. Alpha 2-adrenoceptors are located pre- and
      postsynaptically both in the central noradrenergic pathways and on the autonomic
      nerve endings. It is difficult to dissociate alpha 2-adrenoceptor-mediated
      autoregulation, involving presynaptic receptors, from actions dependent on post-
      and extrajunctional alpha 2-adrenoceptor activation. A lot of alpha 2
      adrenoceptors are subject to permanent tonic activation by the sympathetic
      nervous system. Max Lafontan and colleagues review the major actions of alpha 2
      adrenoceptors and consider the sites of impact of alpha 2-antagonists that could
      initiate further research for putative applications of these drugs. Many of the
      possible targets for alpha 2-adrenoceptor antagonists have not yet been explored
      clinically.

PMID- 1354904
TI  - [Pattern of choice in preparation of attempted suicide by poisoning--with
      particular reference to changes in the pattern of prescriptions].
AB  - This investigation was initiated in 1990 to investigate the choice of preparation
      in cases of attempted suicide treated in the Emergency Unit in Odense University
      Hospital during the past decade. The results show that 1) an increase has
      occurred particularly among young women in the use of analgesics obtainable
      without prescription (e.g. 13% of young women employed paracetamol as the toxic
      agent), 2) the number of persons employed dextropropoxyphene did not decrease and
      3) a great increase was observed in the number of cases of poisoning with
      ketobemodoni chloridum. In 1985, several barbiturates were withdrawn from the
      Danish Medical Codex and this was followed by a decrease in the number of cases
      of poisoning among women but not among men. At present, approximately 10% of men
      who poison themselves still employ barbiturates. The number of cases of poisoning
      with barbiturates in men is thus not reduced but phenobarbital is the preparation
      of choice. The authors conclude that more attention and care should be paid when
      prescribing dextropropoxyphene, ketobemodoni chloridum and phenobarbital and the
      availability of paracetamol without prescription must be debated critically.

PMID- 1354905
TI  - Nitric oxide mediates relaxation in rabbit and human corpus cavernosum smooth
      muscle.
AB  - We investigated in vitro the relaxant effect of exogenous acetylcholine (ACh) and
      electric-field stimulation (EFS) on rabbit and human corpus cavernosum smooth
      muscle strips (CC) precontracted with phenylephrine. The effects of EFS and ACh
      were monitored alone, after muscarinic receptor blockade and after inhibition of
      nitric oxide (NO) formation with L-N-nitro-arginine (L-NOARG). In rabbit and
      human CC, both atropine and L-NOARG abolished the relaxant effects of ACh. The
      relaxant effects of EFS, however, were only slightly reduced by atropine to 97.5
      +/- 17.5% in human CC and to 89.0 +/- 6.1% in rabbit CC. L-NOARG further reduced
      the EFS effects to 0.8 +/- 1.7% in human CC and to 16.2 +/- 8.7% in rabbit CC. In
      strips obtained from impotent patients with diabetes mellitus, the relaxant
      effects appeared to be significantly less than in strips from nondiabetic
      impotent men. Tetrodotoxin blocked the relaxant EFS effects in human and rabbit
      strips completely. The data indicate the important role of NO in cholinergically
      induced relaxation of cavernous smooth muscle in rabbits and humans. Our findings
      support the idea of NO as the nonadrenergic noncholinergic neurotransmitter in
      penile erection in both species. Rabbit erectile tissue might serve as an in
      vitro animal model for further investigation.

PMID- 1354908
TI  - [Third generation beta blockers in the treatment of hypertension].
AB  - Beta-blockers of the third generation are hybrid antihypertensive drugs which
      reduce the blood pressure by two mechanisms--by beta-blocking and by a dilatating
      action. The author presents experience assembled in Czechoslovakia with
      bopindolol and nebivolol which belong into the class of these substances.
      Treatment with beta-blockers is effective also in hypertension in elderly
      subjects. The author mentions a group of extensive investigations conducted
      abroad, comparing beta-blockers and diuretics in the treatment of hypertension.
      From the analysis it is apparent that beta-blockers exert a favourable effect
      also in primary prevention of ischaemic heart disease. In the conclusion the
      author deals with the strategy of treatment of hypertension associated with other
      diseases, using different types of beta-blockers.

PMID- 1354907
TI  - Acute poisonings with ethyle loflazepate, flunitrazepam, prazepam and triazolam
      in children.
AB  - Even though acute poisonings with benzodiazepines are extremely common, less is
      known of the clinical toxicity of recent derivatives, particularly in children.
      1,989 cases involving ethyle loflazepate, flunitrazepam, prazepam or triazolam
      recorded at the Lyons Poison Center and due to 1 compound and associated with
      clinical symptoms were selected for study. Children less than 16-y of age
      accounted for 482 cases. Sleepiness, agitation and ataxia were significantly more
      frequent in the children. Hypotonia was seldom observed but was indicative of
      severe poisoning. The dangerous toxic dose of these compounds in children is
      suggested to be 0.78-0.90 mg ethyle loflazepate/kg, 0.26-0.29 mg
      flunitrazepam/kg, 7.80-9.00 mg prazepam/kg and 0.06-0.07 mg triazolam/kg. These
      results are in keeping with the relatively low acute toxicity of the older
      benzodiazepines.

PMID- 1354906
TI  - Alpha-adrenoceptor function before and after chemical sympathectomy in human and
      feline detrusor muscles.
AB  - Isolated bladder segments from man and cat were treated with 6-hydroxydopamine (6
      OHDA) in vitro. Chemical sympathectomy was evaluated with fluorescence microscopy
      and found to be very similar to the effect of 6-OHDA administered in vivo to
      cats. Isometric smooth muscle contractile responses were induced by field
      stimulation (FS). The amplitude of the responses increased after denervation. The
      effects of alpha-adrenoceptor agonists and antagonists on the FS-induced
      contractile responses were compared before and after treatment with 6-OHDA. The
      reduction in the contractile responses after the addition of noradrenaline to the
      feline bladder strips was more pronounced after treatment. Phentolamine induced
      an increase in contractile responses before treatment, an effect not seen
      afterwards in human bladder strips but which persisted in feline bladder strips.
      Selective alpha-adrenoceptor agonists did not alter the contractile responses in
      denervated strips. It is suggested that the function of the alpha-adrenoceptors
      in the detrusor is to inhibit neuronally mediated contractile responses of smooth
      muscle.

PMID- 1354909
TI  - International Workshop on CEDIA Assays. Vienna, 1-3 September 1991.

PMID- 1354910
TI  - [Drug prevention and therapy of acute gastroduodenal lesions (stress ulcers)].
AB  - The incidence of acute lesions of the gastroduodenal mucosa is high in intensive
      care patients. A disturbed balance between aggressive and defensive factors is
      the cause of the mucosal damage. H2-receptor antagonists reduce gastric acidity,
      the most important aggressive agent, and are, therefore, still the drugs of
      choice for the prevention of stress ulcerations. Bleeding from mucosal lesions is
      the most common complication of stress ulcers. In addition to endoscopic and
      surgical techniques to stop bleeding, and prevent rebleeding, medical treatment
      with drugs like omeprazole have gained importance in recent years.

PMID- 1354911
TI  - Carrier detection in agammaglobulinemia by X chromosome inactivation analysis.
AB  - Using a recently developed strategy to analyze patterns of X chromosome
      inactivation in cell populations, we found that two mothers and a sister were
      carriers in three atypical or sporadic cases of patients with agammaglobulinemia,
      two of whom were brothers. In this study, a phosphoglycerate kinase 1 (PGK1) gene
      probe was used to detect patterns of methylation of X-chromosome genes. A random
      pattern of X inactivation was observed in isolated peripheral blood granulocytes.
      In contrast, one of the two X chromosomes was preferentially active in the
      Epstein-Barr virus (EBV)-transformed peripheral B cells of the family members of
      these patients. The volume of the blood specimen could be significantly reduced
      using EBV-transformed B cell lines which contained multiple clones. The analysis
      described here can be used to distinguish between X-linked agammaglobulinemia
      (XLA) and other forms of a- or hypo-gammaglobulinemia as well as to detect the
      carrier state.

PMID- 1354912
TI  - Neurosteroids: an overview.

PMID- 1354913
TI  - Different sites of action of neurosteroids and benzodiazepines on natural and
      recombinant GABAA receptors.

PMID- 1354914
TI  - Pharmacology of a GABAA receptor coupled steroid recognition site.

PMID- 1354915
TI  - Pharmacologically distinct GABAB receptor subtypes modulate neurotransmitter
      release in the rat brain cortex.

PMID- 1354916
TI  - "Peripheral" benzodiazepine recognition sites may be involved in the rapid
      tolerance to the sedative effects of benzodiazepines in rats.

PMID- 1354917
TI  - Tolerance to anticonvulsant effects of clobazam, diazepam, and clonazepam in
      genetically epilepsy prone rats.

PMID- 1354918
TI  - GABA- and glutamate-gated ion channels as molecular sites of alcohol and
      anesthetic action.
AB  - The evidence presented above indicates that GABA- and glutamate-activated ion
      channels are molecular sites of alcohol and anesthetic action. In view of the
      important role that these channels play in CNS excitability, it seems likely that
      the actions of alcohol and anesthetics on these channels contribute significantly
      to the behavioral effects of these agents. Although the behavioral effects of
      alcohol and anesthetics may well result from a combination of actions on
      different ion channels and other molecular sites in the CNS, it is of interest to
      consider whether the actions of these agents on particular types of ion channels
      may contribute to particular behavioral effects. In this regard, it should be
      noted that benzodiazepines potentiate GABAA responses, but do not produce
      intoxication or general anesthesia in their clinical dose range. Benzodiazepines
      are widely used clinically, primarily for their anxiolytic actions (26),
      suggesting that the potentiation of GABAA responses by ethanol and barbiturates
      may contribute to the anxiolytic effects of these agents. Since kainate and
      quisqualate channels mediate fast excitatory transmission in the CNS, inhibition
      of kainate and quisqualate receptor-activated responses would be expected to
      result in general CNS depression. This suggests that inhibition of kainate and
      quisqualate receptor-mediated responses may contribute to the general anesthetic
      effects of ethanol, trichloroethanol and barbiturates. NMDA channels are thought
      to mediate complex excitatory neural phenomena and cognitive function. In view of
      this, the observation that ethanol inhibits NMDA receptor-mediated responses over
      the concentration range that produces intoxication and the correlation between
      the potency of different alcohols for inhibiting NMDA-activated current and their
      potency for producing intoxication suggest that ethanol-induced inhibition of
      NMDA receptor-mediated responses may contribute to the intoxicating effects of
      ethanol. Although these speculations are no doubt oversimplifications, the
      recognition that GABA- and glutamate-gated ion channels are molecular sites of
      alcohol and anesthetic action provides a basis for investigating the molecular
      mechanisms involved in the action of these agents and the behavioral significance
      of those actions.

PMID- 1354919
TI  - What are the differences between abecarnil and conventional benzodiazepine
      anxiolytics?

PMID- 1354920
TI  - The first double-blind, placebo-controlled trial of a partial benzodiazepine
      agonist, abecarnil (ZK 112-119), in generalized anxiety disorder.

PMID- 1354921
TI  - Functional modulation of cloned GABAA receptors expressed in Xenopus oocytes.

PMID- 1354922
TI  - Neurosteroids and GABAA receptor function.

PMID- 1354923
TI  - Taurine: nutritional value and mechanisms of action. Proceedings of the Waltham
      Symposium on Taurine and Cat Nutrition and of the International Taurine
      Symposium. Orange Beach, Alabama, October 8-10, 1991.

PMID- 1354924
TI  - L-glutamate-induced swelling of cultured astrocytes.

PMID- 1354925
TI  - GABA and taurine serve as respectively a neurotransmitter and an osmolyte in
      cultured cerebral cortical neurons.

PMID- 1354926
TI  - Potassium-stimulated release of taurine in a crude retinal preparation obtained
      from the rat is calcium independent.

PMID- 1354927
TI  - Levocabastine: pharmacological profile of a highly effective inhibitor of
      allergic reactions.
AB  - Levocabastine, selected from a series of cyclohexylpiperidine derivatives
      protects rats from compound 48/80-induced anaphylactic shock for at least 16 h at
      the oral dose of 0.0015 mg/kg. At the same dose histamine skin reactions and at
      slightly higher doses passive cutaneous anaphylactic reactions are inhibited.
      Blockade of passive cutaneous anaphylactic reactions is obtained with
      levocabastine, despite absence of peripheral serotonin antagonism and any other
      known non-specific action that may facilitate inhibition of passive anaphylaxis.
      In dogs allergic reactions are inhibited at oral doses 40 times lower than
      ketotifen. In guinea-pigs orally and topically administered levocabastine are
      remarkably effective against allergic conjunctivitis.

PMID- 1354928
TI  - Epidemiology of Plasmodium falciparum in a rice field and a savanna area in
      Burkina Faso. Comparative study on the acquired immunoprotection in native
      populations.
AB  - A longitudinal study, including entomological, parasitological, immunological and
      clinical data, was carried out in a rice field and a savanna village in Burkina
      Faso. In this study, the authors followed the evolution of several
      parasitological parameters in order to compare the level of immunoprotection in
      children of these two areas. In particular, the percentages of recently
      'infected' or 'recovered' children were calculated, during the interval
      separating two consecutive surveys. In both areas, parasite densities quickly
      increased in children from 0 to 14 years old, immediately after the beginning of
      the transmission period. In savanna, during the rainy season (May-October),
      parasite densities decreased and the proportion of recently 'recovered' children
      from 0 to 4 years old (becoming parasitologically negative between two
      consecutive surveys) was very low. On the other hand, parasite densities
      decreased and the recovery rate was higher in children from 10 to 14 years old
      before the end of the rainy season, while the transmission was going on. In the
      rice field area, Plasmodium falciparum densities decreased only at the end of the
      transmission period (December) and had the same levels as those found in savanna,
      in spite of a lower inoculation rate. The second peak of transmission seemed
      neither to increase the proportion of recovered children, nor to boost the
      immunoprotection of these children.

PMID- 1354929
TI  - Failure of chemoprophylaxis against bovine trypanosomiasis on Galana Ranch in
      Kenya.
AB  - The duration of prophylaxis provided by 1 mg kg-1 bodyweight of homidium bromide
      was compared with that provided by 1 mg kg-1 bodyweight of isometamidium chloride
      in a 12 month field trial involving 90 Boran cattle exposed to trypanosome
      challenge on Galana Ranch in Kenya. Weekly trypanosome prevalences of over 30%
      were observed during 4 of the 12 months. During these periods of heavy challenge,
      parasites were detected 2-3 weeks after administration of both homidium bromide
      and isometamidium chloride. Both prophylactic drugs were administered, on a group
      basis, eight times over the 12 month trial and in addition individual infections
      were also treated with diminazene aceturate. Isometamidium chloride provided
      slightly longer periods of prophylaxis than homidium bromide, 28.4 days compared
      with 25.4 days. There was a highly significant difference in the productivity of
      the two groups during a period of poor grazing. 27% of the isometamidium chloride
      herd died from a severe wasting condition with substantial liver damage evident
      on post mortem. The condition was not observed in the homidium bromide herd. The
      surviving animals in the isometamidium chloride herd had a mean annual weight
      gain of 24 kg less than that recorded in the homidium bromide herd.

PMID- 1354930
TI  - Absence of the LiTat 1.3 (CATT antigen) gene in Trypanosoma brucei gambiense
      stocks from Cameroon.
AB  - Antibodies to the variable antigen type (VAT) designated LiTat 1.3 are common in
      sera from parasitologically confirmed patients with gambian sleeping sickness.
      For this reason, LiTat 1.3 has been considered a suitable antigen for detecting
      Trypanosoma brucei gambiense in the Card Agglutination Test for Trypanosomiasis
      (CATT; Testryp-CATT, Smith Kline-RIT). However, surveys in the T.b. gambiense
      endemic focus of Fontem in Cameroon have suggested that expression of LiTat 1.3
      might be rare or absent. We show here that the gene for LiTat 1.3 was indeed
      absent from some T.b. gambiense stocks isolated from this focus, and a LiTat 1.3
      like gene was present in others. The divergent gene differed from the cloned
      version of LiTat 1.3. In addition, antibodies to LiTat 1.3 could not be detected
      in rabbits infected with either of the two kinds of T.b. gambiense from the
      Fontem area. We suggest that the absence of LiTat 1.3 expression in this focus
      may have important implications for the epidemiology and control of sleeping
      sickness, especially if heavy reliance is placed on the CATT.

PMID- 1354931
TI  - The antibody response to well-defined malaria antigens after acute malaria in
      individuals living under continuous malaria transmission.
AB  - The IgG and IgM antibody responses to the C-terminal 783 amino acids of the P.
      falciparum glutamate-rich protein, GLURP489-1271, expressed as an E. coli fusion
      protein, the IgG response to a 18-mer synthetic peptide EDKNEKGQHEIVEVEEIL
      (GLURP899-916) representing the C-terminal repeats of GLURP, and a synthetic
      peptide (EENV)6 representing the C-terminal repeats from Pf155/RESA, were
      investigated longitudinally in 13 children and 7 adults living under conditions
      of continuous, intense malaria transmission. Some subjects did not recognize the
      antigens after malaria infection, and in subjects recognizing the antigens, the
      responses were often short-lived. In adults, the antibody responses to the
      GLURP489-1271 fusion protein and the (EENV)6 peptide peaked after 2 weeks, and
      not all individuals responded to all antigens. The antibody response, even
      against large fragments of conserved antigens, is not uniformly elicited by
      natural malaria infection in previously primed donors.

PMID- 1354932
TI  - Eye lesions, blindness and visual impairment in the Taraba river valley, Nigeria
      and their relation to onchocercal microfilariae in skin.
AB  - 2876 persons in fourteen communities in the Taraba River Valley, Nigeria were
      examined for eye lesions and tested for visual acuity using the 'tumbling E'. The
      individuals were also examined for microfilaria of Onchocerca volvulus. More than
      one-tenth of the population were blind, while another 16.1% had visual
      impairment. The prevalence of blindness was in excess of 20% in six communities,
      with one community recording 71.9% blindness rate. All forms of visual
      involvement increased with age but were similar between sexes. Eye lesions were
      related to the level of vision. Both eye lesions and vision deteriorate with
      increase in age. Vision seems to worsen with increase in prevalence and intensity
      of O. volvulus. Large microfilarial loads were associated with severe eye damage
      and blindness. These findings indicate that the Taraba river valley could be one
      of West Africa's worst foci of onchocercal blindness.

PMID- 1354933
TI  - Evaluation of haematuria as an indirect screening test for schistosomiasis
      haematobium: a population-based study in the White Nile province, Sudan.
AB  - Haematuria elicited in the history, seen macroscopically or detected by reagent
      strips, was used as an indirect screening test for Schistosoma haematobium
      infection in Um-Hani Irrigation Scheme in the White Nile province, Sudan. These
      approaches were used separately or combined in different sequences. Reagent
      strips alone detected 81% of cases and 88% of those who excreted 50 egg/10 ml of
      urine or more. The sequence of observation of gross haematuria followed by
      screening with reagent strips and then taking history of haematuria had the
      highest sensitivity of all the orders, 0.87, and it saved 18% of reagent strips.
      If history and inspection were done first, followed by reagent strips, the
      sensitivity would be 0.86 and 47% of strips would be saved. The specificity of
      haematuria as a diagnostic index for schistosomiasis, however, was low.

PMID- 1354934
TI  - Glossina fuscipes fuscipes and Glossina palpalis palpalis as joint vectors of
      sleeping sickness in the focus of Nola-Bilolo in the Central African Republic.

PMID- 1354935
TI  - The isolation of the sheath/epicuticle of Brugia pahangi microfilariae.

PMID- 1354936
TI  - A symposium: Use of flecainide for the treatment of supraventricular arrhythmias.
      Amsterdam, The Netherlands, August 17, 1991.

PMID- 1354937
TI  - Effect of maximal medical therapy on refractoriness of unstable angina pectoris.
AB  - A group of 125 patients with unstable angina were studied over a 5-year period to
      define the incidence of refractory unstable angina in the current era of 5-drug
      medical therapy with intravenous heparin, aspirin, nitrates, calcium antagonists
      and beta blockers. All patients had greater than 20 minutes of chest pain at rest
      with reversible electrocardiographic changes occurring in the absence of
      myocardial infarction. Patients were considered refractory only if chest pain
      continued despite treatment with maximal 5-drug therapy. At the time of transfer
      to the center, 65 patients continued to have ischemic chest pain at rest and were
      considered "medically refractory" by their referring physicians. A more
      aggressive medical regimen was used, and 54 patients (83%) were rendered chest
      pain-free. Of the 11 truly refractory patients (8.8%), coronary arteriography
      revealed an increased likelihood of left main or 3-vessel disease (7 of 11 vs 26
      of 114; p = 0.01). In-hospital treatment strategies for the 114 patients
      stabilized with medical therapy included continued medical therapy (n = 37),
      coronary angioplasty (n = 46) and bypass grafting (n = 31). The rate of
      myocardial infarction or death in patients managed medically was 3%. Coronary
      angioplasty in medically stabilized patients was complicated by an abrupt closure
      rate of 26%, and a 17% rate of myocardial infarction, death or need for emergency
      bypass grafting. Medically stabilized patients undergoing bypass grafting had a
      9% rate of myocardial infarction or death. Unstable angina truly refractory to
      current, maximal medical therapy is infrequent (8.8%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1354939
TI  - The Bethesda System for reporting cervical/vaginal cytologic diagnoses. Report of
      the 1991 Bethesda workshop.

PMID- 1354938
TI  - Effects of acute and chronic ibopamine administration on resting and exercise
      hemodynamics, plasma catecholamines and functional capacity of patients with
      chronic congestive heart failure.
AB  - The effects of acute and chronic ibopamine treatment on resting and exercise
      hemodynamics, exercise capacity and plasma catecholamines were evaluated in 25
      patients with chronic heart failure, using a double-blind, parallel, placebo
      controlled design. During 2 months of therapy with either placebo or ibopamine
      (100 mg, 3 times daily), 1 patient was withdrawn from each group for worsening
      heart failure, New York Heart Association functional class improved in 4 patients
      on ibopamine and in 1 on placebo, and furosemide dose could be decreased in 4 on
      ibopamine and in no patient on placebo. Acute ibopamine administration induced,
      in comparison with placebo, a significant increase of cardiac and stroke volume
      indexes both at rest and peak exercise, with a reduction of systemic vascular
      resistance. These hemodynamic changes were maintained also after chronic therapy,
      with no evidence of tolerance development. Exercise capacity (evaluated as peak
      exercise duration and oxygen consumption, and ventilatory threshold) did not
      significantly change. Resting and peak exercise norepinephrine plasma levels were
      significantly reduced after both acute and chronic ibopamine administration.
      Thus, the hemodynamic and neurohumoral effects of ibopamine make this drug
      potentially useful for the chronic treatment of congestive heart failure.

PMID- 1354940
TI  - The proliferative cell fraction in cytology specimens. A study of human
      esophageal carcinoma.
AB  - Immunostaining of cell cycle-related antigens, especially Ki-67, DNA polymerase
      alpha, and proliferating cell nuclear antigen, has become an important method to
      assess the proliferative activity of tumors. These three nuclear antigens were
      studied by immunohistochemical analysis of cytologic smears. These smears were
      obtained by scraping the cut surface of 10 cases of esophageal squamous cell
      carcinoma and were fixed and prepared by different methods. The results were
      compared with those of tissue sections to apply the immunocytochemical findings
      of these antigens to cytology specimens. Smears that were placed on Denhardt- or
      Neoprene-coated slides and subsequently fixed in 4% paraformaldehyde and methanol
      exhibited the best cell adherence to the slides, had minimal loss of
      antigenicity, and had good preservation of cell morphologic features for all
      three antigens examined. The percentage of positive tumor cells in the cytology
      smear was generally in good agreement with that in the tissue section. For these
      three antigens, proliferating cell nuclear antigen demonstrated a much higher
      percentage of positive cells than either Ki-67 or DNA polymerase alpha, in both
      the smears and the tissue sections. In summary, Ki-67, DNA polymerase alpha, and
      proliferating cell nuclear antigen can be immunolocalized successfully in
      cytology smears and may become another parameter to assess the proliferative
      activity of tumors in the field of diagnostic pathology.

PMID- 1354941
TI  - Hormone and autacoid regulation of cAMP production in rat IMCD subsegments.
AB  - The inner medullary collecting duct (IMCD) of the rat consists of two
      structurally and functionally distinct segments, i.e., the initial and the
      terminal IMCD. To identify factors that may regulate the transport function in
      the IMCD segments, we assessed whether catecholamines, carbachol, prostaglandin
      E2 (PGE2), bradykinin, glucagon, calcitonin, parathyroid hormone, or epidermal
      growth factor affects adenosine 3',5'-cyclic monophosphate (cAMP) production in
      microdissected tubules in the presence and absence of arginine vasopressin (AVP,
      0.1 nM). All experiments were performed in the presence of 3-isobutyl-1
      methylxanthine, and cAMP was measured by radioimmunoassay. Epinephrine (greater
      than or equal to 50 nM) and clonidine (greater than or equal to 1 microM)
      markedly decreased AVP-induced cAMP levels in both IMCD segments. However,
      phenylephrine did not show an effect. The inhibitory effect of epinephrine was
      blocked by yohimbine (50 nM) but not by prazosin (50 nM). In isolated perfused
      terminal IMCDs, epinephrine inhibited AVP-stimulated urea permeability.
      Isoproterenol (1 microM), in the absence of AVP, caused a significant increase in
      cAMP level only in the initial IMCD. Propranolol (1 microM) inhibited this
      isoproterenol effect, but atenolol did not. Dopamine (less than or equal to 1
      microM) had no effect on cAMP levels in either IMCD segment. Carbachol, PGE2, and
      the various peptide hormones had no effect on cAMP levels (+/- AVP) in either
      IMCD segment. We conclude that an adrenergic beta 2-receptor is present only in
      the initial IMCD, where its occupation increases cAMP production. We conclude
      also that an adrenergic alpha 2-receptor is present in both IMCD segments, where
      its occupation inhibits AVP-induced cAMP production.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1354942
TI  - Characteristics and development of myocardial stunning in the pig.
AB  - Regional left ventricular function associated with consecutive ischemic periods
      of 2, 2, 5, 10, and 2 min was recorded by ultrasonic technique in pentobarbital
      anesthetized pigs. All systolic and diastolic derangements first appeared after 5
      min of ischemia, and all worsened after 10 min of ischemia. Percent systolic
      segment length shortening reached nadirs 23 (17-29)% (P less than 0.001) and 54
      (45-65)% (P less than 0.001) below baseline 30 min after 5 and 10 min of
      ischemia. During reperfusion all recorded systolic and diastolic variables
      transiently recovered and then deteriorated with a closely similar time course.
      This covariance indicates that systolic and diastolic derangements are causally
      related, and because diastolic compliance was preserved in stunned myocardium we
      conclude that all derangements largely result from reduced systolic tension
      development. Transient postischemic hypercontractility followed all occlusions
      and was not attenuated by beta-blockade and not mimicked by hyperemia alone.
      Postischemic hypercontractility was greatly enhanced in stunned myocardium, and
      we hypothesize that more pronounced and sustained postischemic elevation of
      intracellular Ca2+ concentration explains this observation.

PMID- 1354943
TI  - Surgical and pharmacological dissociation of cardiovascular and emetic responses
      to intragastric CuSO4.
AB  - Under control (intact and laparotomized) conditions, arterial pressure of urethan
      anesthetized ferrets rose significantly in response to intragastric copper
      sulfate (CuSO4; 10 ml of 5 mg/ml). CuSO4 was emetic 75-90% of the time, and a
      cardiovascular response always immediately preceded and accompanied emetic
      responses. The cardiovascular response was significantly reduced or abolished by
      hexamethonium (0.35 mg/kg) pretreatment combined with atropine methyl bromide (1
      mg/kg). Addition of the alpha 2-receptor antagonist 2,3-dichloro-alpha
      methylbenzylamine HCl (DCMB, 10 mg/kg) and the beta-receptor antagonist
      propranolol (3 mg/kg) to the hexamethonium and atropine combination prevented its
      reduction of the cardiovascular response. Given individually, these agents did
      not alter cardiovascular response, nor did yohimbine (0.30 mg/kg), RS(+/-)
      zacopride (0.30 mg/kg), or granisetron (0.50 mg/kg). Only RS(+/-)-zacopride
      significantly reduced incidence of emesis. Atropine methyl bromide alone, with
      hexamethonium, or with hexamethonium, propranolol, and DCMB significantly delayed
      the first emetic episode. Conversely, bilateral abdominal vagotomy significantly
      reduced the number of vomiting animals without affecting cardiovascular response.
      These results suggest that the neural pathways mediating the two events are not
      identical. In another series of experiments, a significantly greater proportion
      of animals vomited in response to intragastric CuSO4 than to intraduodenal CuSO4,
      suggesting that the primary site of CuSO4 action in the ferret is the stomach.

PMID- 1354944
TI  - Excitatory amino acids may mediate nucleus tractus solitarius input to rat
      parabrachial neurons.
AB  - The pontine parabrachial nucleus (PBN) is a recipient of predominantly excitatory
      input from the nucleus of the solitary tract (NTS). The presence of glutamate
      like immunoreactivity at these brain stem sites suggests a role for excitatory
      amino acids (EAAs) in neurotransmission within the projection. We utilized
      electrophysiological studies in vivo to examine the ability of specific EAA
      antagonists, applied locally, to alter glutamate (GLU)-induced and NTS-evoked
      excitation of PBN neurons. Nonselective EAA antagonist kynurenic acid (KYN), the
      selective N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonovalerate
      (APV), and non-NMDA quinoxalinedione group of blockers 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX) and 6-nitro-7-sulfamobenzoquinoxaline-2,3-dione (NBQX) were
      applied by iontophoresis or micropressure ejection from multibarreled pipettes
      attached to the recording electrode. Extracellular recordings in urethan
      anesthetized rats were obtained from 58 PBN neurons that displayed an excitatory
      response following electrical stimulation within the NTS. Poststimulus histogram
      data revealed that NTS-evoked excitation could be reversibly blocked by KYN, APV,
      and CNQX in 21/37 (57%), 11/21 (52%), and 10/19 cells (53%), respectively. Both
      NMDA and non-NMDA antagonists reversibly attenuated or blocked GLU-evoked
      excitation in 21 of 29 PBN neurons. These observations suggest a role for both
      NMDA and non-NMDA receptors in mediating the excitatory input from NTS to the
      PBN.

PMID- 1354945
TI  - Influence of levocabastine suspension on ciliary beat frequency and mucociliary
      clearance.
AB  - The effects of levocabastine, a new fast-acting, highly potent H1-antagonist, on
      nasal ciliary epithelial function were investigated in an in vitro and in vivo
      study. In the in vitro study, a suspension of levocabastine in Locke-Ringer
      solution was applied to 10 bioptic specimens of ciliated human adenoid tissue.
      Each specimen was exposed to the test solution for 60 min. Ciliary beat frequency
      (CBF) was recorded with a photoelectric recording device at 10-min intervals.
      There were small, insignificant decreases in CBF, which were minimal compared to
      that observed with ciliotoxic agents. In the in vivo study, 8 healthy volunteers
      were given, intranasally, one droplet of the levocabastine suspension.
      Mucociliary transit time (MTT) was measured by placing a saccharin particle
      drenched in indigo carmine in the nose just below the top of the concha and
      measuring the time until appearance of the dye in the pharyngeal cavity. No
      statistically significant differences were found in the MTT before and after
      application of the levocabastine suspension. The studies thus indicate that
      nasally administered levocabastine does not interfere with ciliary beat frequency
      and mucociliary function.

PMID- 1354946
TI  - Effects of atipamezole, an alpha 2-adrenoceptor antagonist, on the anesthesia
      induced by barbiturates and medetomidine.
AB  - We studied the effects of atipamezole, an alpha 2-adrenoceptor antagonist, on
      hypnosis induced by medetomidine, an alpha 2-adrenoceptor agonist (1 mg/kg IP),
      and pentobarbital (40 mg/kg IP) by testing the righting reflex in the rat. The
      duration of antinociception was assessed with repeated pinch tests. Medetomidine
      induced hypnosis and antinociception were inhibited by atipamezole at doses
      greater than 0.1 mg/kg. Atipamezole restored the righting reflex at a dose ratio
      that was 1:10 or more to that of medetomidine used to induce hypnosis.
      Subcutaneous atipamezole (1.5 mg/kg) increased the duration of hypnosis induced
      by pentobarbital (40 mg/kg) and pentobarbital + medetomidine (0.3 mg/kg).
      Hypnosis induced by methohexital (60 mg/kg IP) was also prolonged by atipamezole.
      The capacity of atipamezole to reverse the effects of medetomidine is also
      reduced in the presence of barbiturates. Thus, atipamezole should be used only at
      low doses to reverse a combination anesthesia induced by barbiturates and
      medetomidine.

PMID- 1354947
TI  - Resistance to curare, upper motor neuron dysfunction, and antiepileptic
      treatment.

PMID- 1354948
TI  - Which patients benefit from adding theophylline to beta 2-agonist treatment in
      severe acute asthma?
AB  - The aim of this investigation was to study whether certain patients benefit from
      adding theophylline to the beta 2-agonist treatment of acute asthma. The study
      group comprised 101 patients who were taking oral theophylline. The patients
      received inhaled salbutamol (albuterol) (0.15 mg/kg x 2) (n = 53) or IV
      salbutamol (5 micrograms/kg) (n = 48). Aminophylline (3 mg/kg) was infused
      intravenously 60 minutes after the start of the salbutamol treatment. The mean
      increase in peak flow (PEF) after the aminophylline infusion was 22 +/- 33 L/min
      or 4% +/- 6% of the predicted value (mean +/- SD). A change in PEF correlated
      negatively to plasma theophylline before treatment (P less than .01) and
      positively to a change in plasma-theophylline after treatment (P less than .05).
      All patients with an increase in PEF of more than 10% of the predicted value (n =
      14) after the theophylline infusion had plasma-theophylline levels before
      treatment of below 7.5 mg/L (41 mumol/L). No significant difference in the change
      in PEF after the theophylline infusion was found between patients who had
      received inhaled or intravenous salbutamol. This investigation could indicate
      that IV theophylline as an additive to beta 2-agonist treatment should be
      reserved for patients who are either not taking theophylline or who have only
      taken a low dose before arriving for the emergency treatment of acute asthma.

PMID- 1354949
TI  - Pharmacodynamics and pharmacokinetics of mizolastine (SL 85.0324), a new
      nonsedative H1 antihistamine.
AB  - The antihistaminic activity, clinical safety, and pharmacokinetics of mizolastine
      (SL 85.0324) were studied in a 5-way, double-blind crossover study of ten healthy
      volunteers with doses of 1 to 75 mg. Inhibition of the histamine-induced wheal
      and flare showed clear dose-dependent antihistaminic activity beginning from the
      2-mg dose with a maximum attained between 10 and 20 mg. The onset of action was
      rapid (one hour) and the effect persisted for more than 24 hours after a 10-mg
      dose or more. Mizolastine was well tolerated at doses up to 75 mg; subjective and
      objective signs of transient sedative activity were not observed at doses below
      30 mg. The pharmacokinetic profile (rapid absorption with Tmax congruent to 1 h
      and elimination T1/2 of about eight hours) parallels the pharmacodynamic
      activity. Within the considered dose range, the pharmacokinetics was linear with
      no saturation phenomena.

PMID- 1354950
TI  - Inotropic mechanisms of dopexamine hydrochloride in horses.
AB  - Mechanisms responsible for the positive inotropic effects of dopexamine were
      investigated in 8 halothane-anesthetized horses. The hemodynamic effects of
      increasing infusions of dopexamine (5, 10, 15 micrograms/kg of body weight/min)
      were determined before and after sequential administration of specific
      antagonists. Using glycopyrrolate and chlorisondamine, and atenolol and ICI
      118,551, muscarinic and nicotinic ganglionic, and beta 1, and beta 2-adrenergic
      receptor blockade, respectively, was induced. Dopexamine infusions induced
      increase in heart rate, cardiac output, systolic and mean arterial blood
      pressure, and maximal rate of left ventricular pressure development (+dP/dtmax).
      Right atrial pressure and systemic vascular resistance decreased. Parasympathetic
      and ganglionic blockade attenuated cardiac output, systolic and mean aortic blood
      pressures, and +dP/dtmax responses to dopexamine infusion. Dopexamine-induced
      increase in heart rate was potentiated by parasympathetic and ganglionic
      blockade. beta 1-Adrenergic receptor blockade decreased heart rate, cardiac
      output, arterial blood pressure, and +dP/dtmax from baseline values and markedly
      reduced the response to dopexamine infusion. beta 2-Adrenergic receptor blockade
      induced further decrease in hemodynamic variables from baseline values and
      completely abolished the cardiostimulatory effects of dopexamine on +dP/dtmax.
      These data indicate that baroreflex activity, beta 1- and beta 2-adrenergic
      receptor stimulation may be an important cause of dopexamine's positive inotropic
      effects in horses.

PMID- 1354951
TI  - [Effect of various unsaturated fatty acids on the stability of the erythrocyte
      membrane in the rat].
AB  - In rats restrictive feeding of a half-synthetic diet, with coconut fat as the
      dietary fat, caused an essential fatty acid deficiency with increased osmotic
      fragility of erythrocytes against hypotonic saline solutions. A 60% replacement
      of the coconut fat in the basal diet by pure oleic acid (18:1 n-9) or linoleic
      acid (18:2 n-6) by 0.6% alpha-linolenic acid (18:3 n-3), eicosatrienoic acid
      (20:3 n-3) or eicosapentaenoic acid (20:5 n-3) led, in the case of linoleic acid
      and eicosapentaenoic acid, to a significant decrease in the fragility of rat
      erythrocytes in comparison with the basal diet. The inefficacy of the alpha
      linolenic acid treatment is possibly the consequence of a too low dietary
      supplementation.

PMID- 1354953
TI  - Role of iron and oxidant stress in the normal and parkinsonian brain. Proceedings
      of a symposium. Sarasota, Florida, November 14-17, 1991.

PMID- 1354952
TI  - Diagnosis of familial hypercholesterolemia using DNA haplotype analysis in three
      large families with two hyperlipidemic parents.
AB  - Since the cloning of the human LDL receptor (LDLR) gene, familial
      hypercholesterolemia (FH) can be diagnosed by recombinant DNA technology either
      using restriction enzyme mapping to detect major rearrangements of the gene or
      using restriction fragment length polymorphisms (RFLPs) and linkage analysis in
      family studies. Genotypes and haplotypes of four RFLPs (StuI, ApaII 5', PvuII,
      NcoI) were used to study the inheritance of the detective LDLR gene in three
      families. Diagnosis of FH based on the lipid levels alone was not possible
      because in these kindreds both parents exhibit elevated lipid levels. However, in
      two families using haplotype analysis, elevated cholesterol levels in certain
      relatives could be attributed to the inheritance of a defective LDRL gene and
      thereby distinguished from hypercholesterolemia due to familial combined
      hyperlipidemia. In the third family where both hypercholesterolemic parents
      carried a defective LDLR gene, a case of homozygous FH could be excluded in a
      child by demonstrating the inheritance of a normal LDLR gene.

PMID- 1354954
TI  - Characterization of the chromosomal aac(6')-Ic gene from Serratia marcescens.
AB  - The DNA sequence of the chromosomal aac(6')-Ic gene from Serratia marcescens,
      which had been previously cloned (H. M. Champion, P. M. Bennett, D. A. Lewis, and
      D. S. Reeves, J. Antimicrob. Chemother. 22:587-596, 1988) was determined. High
      pressure liquid chromatographic analysis of extracts prepared from Escherichia
      coli carrying the chromosomal aac(6')-Ic gene on a plasmid confirmed the presence
      of 6'-N-acetyltransferase activity in this strain, which was suggested by the
      aminoglycoside resistance profile. DNA sequence analysis of the cloned 2,057-bp
      PstI fragment revealed several regions of homology to previously characterized
      sequences from GenBank, including the rpoD and tRNA-2 genes of E. coli.
      Subcloning experiments confirmed the coding sequence of the aac(6')-Ic gene to be
      at positions 1554 to 1992. The predicted amino acid sequence of the AAC(6')-Ic
      protein suggested that it was the third member of a family of AAC(6') proteins
      which included a coding region identified between the aadB and aadA genes of
      Tn4000 and an AAC(6') protein encoded by pUO490, which was isolated from
      Enterobacter cloacae. Primer extension analysis suggested that the -35 region of
      the aac(6')-Ic promoter overlapped a large palindromic sequence which may be
      involved in the regulation of the aac(6')-Ic gene. Hybridization experiments
      utilizing a restriction fragment from the aac(6')-Ic gene showed that all S.
      marcescens organisms carried this gene whether or not the AAC(6')-I resistance
      profile was expressed. Organisms other than Serratia spp. did not hybridize to
      this probe.

PMID- 1354955
TI  - Muscarinic receptors in the cerebellar vermis modulate the gain of the
      vestibulospinal reflexes in decerebrate cats.
AB  - 1. The Purkinje (P)-cells of the cerebellar vermis, which exert a prominent
      influence on posture as well as on the gain of vestibulospinal (VS) reflexes, are
      under the control not only of the classic mossy fibers and climbing fibers which
      liberate excitatory amino acids as neurotransmitter, but also of cholinergic
      afferents. The role of these afferents was investigated in precollicular
      decerebrate cats by using the method of local microinjection of cholinergic
      agents into appropriate areas of the cerebellar cortex. 2. Unilateral injection
      into the vermal cortex of the culmen of the non-selective cholinergic agonist
      carbachol (0.25 microliters at 0.5 micrograms/microliters saline) produced a
      postural asymmetry, characterized by a slight decrease of the extensor tonus in
      the ipsilateral forelimb and an increased tonus in the contralateral forelimb.
      Moreover, the gain of the EMG responses of the ipsilateral and the contralateral
      triceps brachii to animal tilt increased significantly, while no significant
      changes in the phase angle of the responses were observed. These effects started
      5-10 min after the injection and persisted for at least 2 hours before
      disappearing. Similar but smaller effects were obtained after injection of
      eserine, an inhibitor of acetylcholinesterase. Thus, the effects could be
      produced by increasing the naturally present amount of acetylcholine (ACh). 3.
      The changes in posture and gain of the VS reflexes described above utilized in
      part at least muscarinic receptors, since effects similar to those induced by
      carbachol injection were also obtained after unilateral microinjection into the
      vermal cortex of the culmen of the muscarinic agonist bethanechol (0.25
      microliters at 0.1 micrograms/microliters). On the other hand opposite effects,
      characterized by an increased postural activity in the ipsilateral forelimb
      associated with a decreased activity in the contralateral forelimb, as well as by
      a reduced gain of the EMG responses of the triceps brachii of both sides to
      animal tilt were observed in other experiments after local microinjection of the
      muscarinic antagonist scopolamine (0.25 microliter at 4-8 micrograms/microliters
      saline). Evidence for muscarinic supersensitivity was obtained following
      repetitive injections of scopolamine into the cerebellar vermis. 4. The area
      which upon injection of the cholinergic agents modified the postural activity as
      well as the gain of the VS reflexes was located within the third and/or the
      fourth folium rostral to the fissura prima (culmen), at the laterality of 1.4-1.8
      mm with respect to the midline.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1354956
TI  - Cloning and expression of the mouse homolog of the human alpha 2-C2 adrenergic
      receptor.
AB  - Three subtypes of alpha 2 adrenergic receptors have been identified in the human
      and rat. The subtype located on human chromosome 2 (alpha 2-C2) is unique in that
      it is expressed mainly in the peripheral tissues and lacks sites for N-linked
      glycosylation. We isolated the gene encoding the mouse homolog of the human alpha
      2-C2 adrenergic receptor (M alpha 2-2H). The deduced amino acid sequence of the M
      alpha 2-2H shows 82% and 96% identity to the human alpha 2-C2 and the rat RNG
      alpha 2 adrenergic receptors, respectively. Southern blot analysis demonstrated
      that the M alpha 2-2H was encoded by a single copy gene and was distinct from the
      mouse homologs of the alpha 2-C4 and alpha 2-C10 adrenergic receptors. When
      expressed in COS-7 cells, the M alpha 2-2H exhibited a pharmacological profile
      similar to the human alpha 2-C2 and rat RNG alpha 2 receptors.

PMID- 1354957
TI  - Heterogeneous responses of recombinant human thyrotropin receptor to
      immunoglobulins from patients with Graves' disease.
AB  - Non-thyroid mammalian cells, CHO-K1 cells, stably expressing human thyrotropin
      receptor (CHO-TSH-R cells) were used for the assay of thyroid stimulating
      antibody (TSAb) activities of IgGs from 24 patients with Graves' disease and we
      compared them with the values obtained in porcine thyroid cells. A significant
      positive correlation was observed between the results given by CHO-TSH-R cells
      (hTSAb) and porcine thyrocytes (pTSAb) (r = 0.94, p less than 0.001). However, we
      found that hTSAb values of IgGs from 5 patients were extremely different from
      their hTSAb values. Four out of these 5 IgGs showed strong pTSAb activity but
      exhibited a weak or negative hTSAb activity. Conversely, one out of 5
      autoantibodies was very strong for hTSAb but its pTSAb was low. These
      heterogeneous responses of recombinant hTSH-R to Graves' IgGs suggest that there
      exist different types of TSAb and also that the epitope(s) for TSAb may be
      different from case to case.

PMID- 1354958
TI  - Conjugated bile acid uptake by Xenopus laevis oocytes induced by microinjection
      with ileal Poly A+ mRNA.
AB  - Apical membranes of ileal enterocytes contain the major Na+/bile acid
      cotransporter activity in mammals. Microinjection of guinea pig ileal mucosal
      Poly A+ mRNA (25 ng) into Xenopus oocytes resulted in 22,23-3H-cholyltaurine
      uptake at day 3 after injection (453 fmol/oocyte-hr), while control viral mRNA
      (25 ng) gave an uptake rate of 133 fmol/oocyte-hr. The transport rate increased
      in direct relationship to the concentration of injected mRNA, cholyltaurine, or
      Na+ in the incubation media. Uptake of cholyltaurine using rabbit ileal mucosal
      Poly A+ mRNA was 3891 fmole/oocyte-hr compared to rabbit jejunal-mucosa Poly A+
      mRNA (control) injections inducing 728 fmol/oocyte-hr. Such expression of the
      ileal Na+/bile acid cotransporter may facilitate cloning of this key mammalian
      gene.

PMID- 1354959
TI  - Inhibition of phosphatidylserine synthesis by glutamate, acetylcholine,
      thapsigargin and ionophore A23187 in glioma C6 cells.
AB  - Phosphatidylserine synthesis was studied in glioma C6 cells with [14C]serine and
      in the presence or absence of agents which increase the level of [Ca2+]i. It was
      found that glutamate and acetylcholine inhibited this synthesis by up to 40%,
      whereas thapsigargin and the ionophore A23187 inhibited by up to 70%. The
      inhibitory effect of thapsigargin and the A23187 was observed in Ca(2+)-free
      medium. The data show that the inhibition of this synthesis is caused by the
      Ca(2+)-depletion from endoplasmic reticulum, suggesting that the synthesis of
      phosphatidylserine occurs on the luminal side of these structures and can be
      regulated by transmembrane signaling systems.

PMID- 1354960
TI  - Cytotoxicity of a new IMP dehydrogenase inhibitor, benzamide riboside, to human
      myelogenous leukemia K562 cells.
AB  - COMPARE computer program suggested that benzamide riboside, BR, 3-(1-deoxy-beta-D
      ribofuranosyl)benzamide, should have a similar mechanism of action as that of
      tiazofurin, an inhibitor of IMP dehydrogenase (IMPDH). This hypothesis was tested
      in K562 cells in culture. BR was cytotoxic to K562 cells with an IC50 of 2
      microM. Incubation of K562 cells with BR resulted in a significant decrease in
      GMP and GTP levels with a concurrent increase in IMP pools, and with a
      significant inhibition of IMPDH activity. However, 290-fold higher BR
      concentration was needed to demonstrate in vitro inhibition of IMPDH activity,
      suggesting that the agent may require metabolism to exert its action. These
      results provide evidence that BR is a new inhibitor of IMPDH. This investigation
      should be helpful to design new analogues having activity against IMPDH.

PMID- 1354961
TI  - The primary structure of rat ribosomal protein S25.
AB  - The amino acid sequence of the rat 40S ribosomal subunit protein S25 was deduced
      from the sequence of nucleotides in a recombinant cDNA. Ribosomal protein S25 has
      125 amino acids and has a molecular weight of 13,733. Hybridization of the cDNA
      to digests of nuclear DNA suggests that there are 19 to 22 copies of the S25
      gene. The mRNA for the protein is about 550 nucleotides in length. Rat S25 is
      homologous to ribosomal proteins from other eukaryotes (human and yeast).

PMID- 1354962
TI  - Hypothalamic hormones modulate G protein levels and second messenger
      responsiveness in GH3 rat pituitary tumour cells.
AB  - Thyroliberin (TRH), vasoactive intestinal peptide (VIP) and somatostatin (SRIF)
      act through receptors that are coupled to guanine nucleotide-binding regulatory
      proteins (G proteins). Regulation of hormone action may occur at the level of G
      protein coupling to the receptor or effector systems. In this study we
      demonstrate that prolonged exposure (for up to 48 hr) of cultured rat pituitary
      adenoma GH3 cells to these hormones caused homologous and to some extent
      heterologous attenuation of the adenylyl cyclase (AC) (EC 4.6.1.1)
      responsiveness. In addition, TRH and SRIF diminished both TRH- and guanosine 5'
      [beta gamma-imido]-triphosphate-enhanced phospholipase C (PLC) (EC 3.1.4.3)
      activity within the same time-course. Measurements of cells membrane levels of Gs
      protein alpha-subunit (Gs alpha), G(i)-1 alpha/G(i)-2 alpha, G(i)-3 alpha, G(o)
      alpha and G beta by immunoblotting were performed. TRH and VIP upregulated levels
      of all G proteins except G(o) alpha and G beta. In contrast, SRIF caused a marked
      reduction of G beta levels. Thus, TRH and VIP, both acting through Gs, both
      modulated the alpha-subunit levels of this signal transducer, whereas SRIF, which
      possibly acts through G(i)-2, did not change the steady state level of G(i)-2
      alpha. The actions of TRH, VIP and SRIF are multifaceted at the G protein level,
      where modulations of subtypes not directly involved in their actions may occur.
      These findings emphasize the complexity expected to be found in the in vivo
      situation.

PMID- 1354963
TI  - Doxorubicin-loaded nanospheres bypass tumor cell multidrug resistance.
AB  - We have demonstrated that in vitro resistance of tumor cells to doxorubicin (Dox)
      can be fully circumvented by using doxorubicin-loaded nanospheres (Dox-NS),
      consisting of biodegradable polyisohexylcyanoacrylate polymers of 300 nm diameter
      and containing 2.83 mg of Dox per 31.5 mg of polymer. Five different multidrug
      resistant cell lines, characterized by mdr1 amplification, were used in this
      study: Dox-R-MCF7, a human breast adenocarcinoma; SKVBL1, a human ovarian
      adenocarcinoma; K562-R, a human erythroleukemia; and two murine lines: P388-Adr
      R, a monocytic leukemia of DBA2 mouse, and LR73MDR, a Chinese hamster ovarian
      cell line. These lines were 38.7, 210, 232, 143 and 20 times more resistant than
      their corresponding sensitive counterparts, respectively. Using Dox-NS, we
      obtained complete reversion of drug resistance in vitro, i.e. cell growth
      inhibition comparable with that obtained with sensitive cells exposed to free
      Dox. In vivo, we significantly prolonged the survival of DBA2 mice which had
      previously received P388-Adr-R cells by i.p. injections of Dox-NS, while free Dox
      injection was ineffective toward this rapidly growing tumor. (Prolongation of
      survival time: 115% vs 167% after Dox vs Dox-NS treatment, respectively.) Using
      the MCF7 cell line and its resistant variant, we studied the intracellular
      concentration and the cytoplasmic and nuclear distribution of Dox by laser
      microspectrofluorometry (LMSF). In sensitive cells, we observed a similar
      accumulation and distribution of Dox whatever the form of Dox delivery, i.e.
      whether free or carried by nanospheres. Analysis by LMSF showed that 99% of
      intranuclear Dox was bound to DNA after treatment with both forms of Dox. Of Dox,
      81 and 83% were found in the intranuclear compartment of sensitive cells
      incubated with free Dox and Dox-NS, respectively. Resistant cells incubated with
      Dox-NS accumulated the same amount of Dox as sensitive cells incubated with free
      Dox or with Dox-NS. Dox, when loaded in nanospheres, bypasses the efflux
      mechanism responsible for multidrug resistance. LMSF analysis showed that Dox,
      transported and released by nanospheres, interacts with DNA identically in
      sensitive and resistant cells.

PMID- 1354964
TI  - Phenylethanolaminotetralines compete with [3H]dihydroalprenolol binding to rat
      colon membranes without evidencing atypical beta-adrenergic sites.
AB  - [3H]Dihydroalprenolol ([3H]DHA) specific binding (determined by the difference in
      the presence and absence of 20 microM (-)isoprenaline) to rat colon membranes was
      saturable (Bmax = 39.6 fmol/mg protein), of high affinity (Kd = 0.87 nM) and
      stereospecific (IC50 330 and 3510 nM for (-)- and (+)isoprenaline, respectively);
      the Hill coefficient was close to one, indicating binding homogeneity. [3H]DHA
      (0.6 nM) specific binding was potently inhibited (Ki range 1.9-3.3 nM) by the non
      selective beta-adrenoceptor antagonists pindolol, alprenolol, but not by the non
      adrenergic compounds 5-hydroxytryptamine, 8-hydroxydipropylaminotetraline,
      methysergide, dopamine and verapamil (Ki greater than 10,000 nM). The selective
      beta 1- and beta 2-adrenoceptor antagonists CGP 20,712A and ICI 118,551 resulted
      in biphasic competition binding curves, whose low and high affinity components
      were compatible with two populations of binding sites accounting for about 75
      (beta 2) and 25% (beta 1) of total sites. The relative competing potencies of
      reference adrenergic agonists also suggested a prevalence of beta 2-adrenergic
      sites. The new agonists phenylethanolaminotetralines (PEATs), highly selective
      for the atypical beta-adrenoceptors whose abundance in rat colon has been
      confirmed by comprehensive functional studies, had variable affinity for the
      [3H]DHA-labelled sites depending on chirality, but with no substantial
      correlation with their pharmacological potency. Only 40% of [3H]DHA binding, at a
      concentration about 10 times its Kd for high affinity sites (beta 1 and beta 2),
      was prevented by saturating concentrations of isoprenaline. Under this condition,
      the representative PEAT, SR 58611A, highly potent and selective for atypical beta
      adrenoceptors in functional tests, and its pharmacologically inactive enantiomer,
      both inhibited the residual binding equipotently. In conclusion, [3H]DHA binding
      did not detect atypical beta-adrenoceptor sites in rat colon membranes, most
      probably because of its weaker affinity for them than for the coexisting beta 1
      and beta 2 sites. PEAT stereoisomers proved essential for assessing both the
      stereospecificity and the functional significance of this atypical binding and to
      compare their affinity for [3H]DHA-labelled sites and pharmacological potency.

PMID- 1354965
TI  - Apoptosis.

PMID- 1354966
TI  - Taking the thymus to pieces.
AB  - Complex in vitro and in vivo techniques are being combined to unlock the
      remaining secrets of the thymus. In this report from a recent thymus workshop*,
      Bruno Kyewski and Thomas Hunig describe the genetic manipulations aimed at
      clarifying the mechanisms of T-cell selection and lineage commitment, and the use
      of organ culture and immunohistology to identify the thymic microenvironments in
      which these events take place.

PMID- 1354967
TI  - Alterations to the cytoskeleton of erythrocytes infected with frog erythrocytic
      virus: a fluorescence and electron microscopic study.
AB  - Erythrocytes of bullfrogs (Rana catesbeiana) infected with frog erythrocytic
      virus are spheroid and their nucleus is displaced. In contrast, uninfected cells
      are ellipsoid and have a centralized nucleus. Fluorescent staining revealed that
      these changes are correlated with alterations to components of the erythrocyte
      cytoskeleton. Uninfected erythrocytes contained a broad, continuous marginal band
      of microtubules, which appeared thinner and interrupted in infected cells. The
      described disruption of microtubules was associated with an inability to
      polymerize the tubulin pool with the addition of 12 microM taxol. The arrangement
      of submembranous microfilaments in uninfected erythrocytes was not significantly
      altered in infected cells. Vimentin filaments were distributed throughout the
      cytoplasm and around the nucleus of uninfected cells, and concentrated at the
      cell and nuclear peripheries. Cytoplasmic pockets that did not contain vimentin
      filaments were associated with the viral assembly site(s) in infected cells.
      These data suggest that the distortion of viral-infected erythrocytes could be
      due, in part, to an irreversible depolymerization of microtubules of the marginal
      band and a reorganization of the vimentin filament network.

PMID- 1354968
TI  - Immunological abnormalities in the natural history of HIV infection: mechanisms
      and clinical relevance.
AB  - Infection with the human immunodeficiency virus (HIV) ultimately results in
      profound immunodeficiency characterized by severe depletion of CD4+ T helper
      cells. In symptomatic infection a general perturbance of immune function is
      observed. Here recent insights in the sequence of events in progression to AIDS
      is reviewed. Following seroconversion a rapid persistent loss of inducible B cell
      function is observed. In addition, in long term infection, antigen-presenting
      cell functions of monocytes and dendritic cells are increasingly affected. T-cell
      non-responsiveness, preceding CD4 cell loss, appears to be induced through
      several different, sequential mechanisms. In early infection, the in-vivo
      deletion of memory cells can account for the in-vitro decreased responsiveness.
      Later on in infection, when the balance between memory and naive T cells is
      normalized, both CD4 and CD8 cells are non-responsive to nominal antigen and low
      dose anti-CD3 monoclonal antibodies. This anergy is at the level of IL-2 gene
      expression since early signal transduction events following CD2 and CD2 receptor
      occupancy are normal. This state of anergy, probably due to inappropriate
      activation in vivo, may be related to programmed cell death (PCD) observed in
      vitro for both CD8 and CD4 cells reflecting a systemic interference with
      maturation and differentiation of T cells. In progression to symptomatic
      infection, the proportion of non-responsive CD8 cells with immature or activated
      phenotypes increases and in about fifty percent of the cases, CD4 cell decline
      may accelerate in association with emergence of syncytium-inducing HIV variants.
      During this progressive stage, anti-CD3 reactivity is severely decreased, and
      alloantigen reactivity and finally the capacity to respond to phytohemagglutinin
      (PHA) are affected. These functional parameters appear useful for staging of HIV
      infected individuals and for evaluation of anti-viral therapy.

PMID- 1354969
TI  - The programmed cell death theory of AIDS pathogenesis: implications, testable
      predictions, and confrontation with experimental findings.
AB  - The programmed cell death theory of acquired immunodeficiency syndrome (AIDS)
      pathogenesis postulates that most immunological and non-immunological defects in
      human immunodeficiency virus (HIV)-infected people are related to a single
      mechanism, the inappropriate expression in mature CD4+ T cells and other cell
      populations such as neurons of an activation-induced physiological cell suicide
      program that plays an essential role during embryogenesis in the maturation of
      both the immune and the nervous systems. The theory is discussed in the context
      of a series of recent experimental findings indicating that mature T cells can,
      as immature thymocytes, undergo programmed cell death in response to T-cell
      receptor mobilization in various physiological and pathological circumstances
      including murine and human acquired immunodeficiency of retroviral origin. These
      findings provide new insights into the pathogenesis of AIDS and may have
      implications for the design of therapeutic strategies.

PMID- 1354970
TI  - Effects of concentration reduction and partial replacement of paraquat by diquat
      on human toxicity: a clinical survey.
AB  - Paraquat poisoning was studied in 174 patients over a 12-month period when a new,
      low concentration paraquat product (4.5% w/v paraquat ion mixed with 4.5% w/v
      diquat ion; 63 cases) replaced the original high concentration paraquat product
      (20% w/v paraquat ion only; 111 cases). In both groups approximately 60% of the
      patients died from circulatory failure accompanied by multiple organ failure
      within a week of ingesting the products. However, a remarkable reduction in late
      deaths from respiratory failure was noted in the new product group (17.1% vs
      6.3%). This was reflected in this group's improved survival (23.4% vs 34.9%). The
      improvement in survival seems to be attributable to the dilution of paraquat with
      diquat which seems to have a different toxicological profile to paraquat.

PMID- 1354971
TI  - Pharmacokinetics of fluazifop-butyl in human volunteers. II: Dermal dosing.
AB  - 1. The absorption of the herbicide fluazifop-butyl (f-b), has been determined
      from plasma and urine measurements in groups of six male volunteers following
      dermal administration of 2.5, 25 and 250 micrograms cm-2 from standardized
      formulations containing 0.05, 0.5 and 5.0% (w/v) fluazifop-butyl to a skin area
      of 800 cm2. 2. Urinary excretion rate of the principal metabolite fluazifop,
      following dosing with the 5% formulation, was described by a two-compartment
      pharmacokinetic model; the average elimination half-lives of initial and terminal
      phases were 18 h and approximately 70 h, respectively. For the other dose levels
      the elimination half-life was estimated to be 17 h; urine concentrations at later
      time points were too low to characterize a second compartment. 3. The estimated
      total fluazifop-butyl absorbed was 8.0, 3.4 and 1.6% of the applied dose for the
      0.05, 0.5 and 5.0% formulations, respectively. 4. Up to 50% of the applied
      fluazifop-butyl was readily removed by skin washing and the majority of the
      remainder was transferred to clothing during the 24 h following application. 5.
      When six volunteers were given a daily dermal dose of the 0.5% formulation for
      five consecutive days, the plasma and urinary excretion kinetics of fluazifop
      could be accurately predicted by simple mathematical extrapolation of the kinetic
      data from the single exposure study at the equivalent daily dose. 6. It is
      concluded that fluazifop-butyl is only slowly and poorly absorbed through human
      skin and has a low potential to accumulate in man.

PMID- 1354972
TI  - Sex hormones and epididymal sperm parameters in rats following sub-chronic
      treatment with hexavalent chromium.
AB  - Testicular atrophy and reduced epididymal sperm count are known to occur after
      i.p. administration of high doses of hexavalent chromium to rats. The effect of
      0.5 mg kg-1 hexavalent chromium injected i.p. 5 d a week for 8 weeks was
      investigated in male Wistar rats. A significant reduction in epididymal sperm
      motility was found at the end of the exposure period. The reduction was reversed
      after an unexposed period of a further 8 weeks. In addition, a decrease in serum
      testosterone and an increase in FSH were found at the end of the exposure period.
      The results indicate that a number of mechanisms may be involved in the
      deleterious effects of chromate on male fecundity.

PMID- 1354973
TI  - Sex hormones and semen quality in welders exposed to hexavalent chromium.
AB  - Recent experimental studies in rodents document the spermatotoxic effects of
      water-soluble hexavalent chromium. Welders comprise, worldwide, a major
      occupational group with acknowledged exposure to chromium. This study examines
      the relationship between semen quality and chromium in the urine and blood of a
      population of 30 tungsten inert gas (TIG) stainless steel welders, 30 mild steel
      welders and 47 non-welding workers. Each subject provided two to three semen
      samples. The chromium concentration ranged from 0.17 to 4.74 nmol mmol1
      creatinine (median 1.08) in post-shift spot urine and from 6.0 to 46.4 nmol l-1
      in blood. None of several semen parameters deteriorated with increasing level of
      internal exposure to chromium. Low-level exposure to hexavalent chromium
      associated with TIG stainless steel and mild steel welding do not appear to be a
      major hazard for human spermatogenesis.

PMID- 1354974
TI  - Long-term anticonvulsant therapy worsens outcome in paracetamol-induced fulminant
      hepatic failure.
AB  - 1. Paracetamol hepatotoxicity has been found to be potentiated by anticonvulsant
      drugs in animal experiments; isolated case reports in humans suggest that long
      term anticonvulsant therapy may also adversely influence outcome following
      overdose. 2. We compared the clinical course, after paracetamol overdose, of 18
      patients on long-term anticonvulsant therapy with corresponding features in two
      published series of paracetamol-induced fulminant hepatic failure from this unit:
      297 patients seen between 1973 and 1985 and a further 99 between October 1986 and
      April 1988. 3. Mortality in those patients who were taking anticonvulsants, but
      who did not receive N-acetylcysteine, was higher than in either of these series
      (93.3% vs 64.6% and vs 57.9%, P less than 0.025). Although not statistically
      significant, there were also trends towards more severe coma (grade 3 or 4: 93.3%
      vs 75.4%, 1986-88), acidosis (pH less than 7.30: 40% vs 22.6%, 1973-85) and
      coagulopathy (prothrombin time greater than 100 s: 53.3% vs 33.7%, 1973-85). In
      the small number of patients given N-acetylcysteine, mortality was similar to
      that in the 1986-88 series (1/3 vs 15/42). 4. We conclude that chronic use of
      anticonvulsants enhances clinical features of paracetamol toxicity and discuss
      possible mechanisms by which this could be mediated.

PMID- 1354975
TI  - Sulphur derivative of hexachlorobenzene in human urine.
AB  - Pentachlorothiophenol, a sulphur derivative of the widespread environmental
      pollutant hexachlorobenzene (HCB) has been detected and quantified in the urine
      of a human general population with high body burden of HCB. The sulphur
      derivative was analysed by GLC-MS as pentachlorothioanisole (PCTA) after
      hydrolysis and methylation of the respective conjugate and was found in 100% of
      the samples (n = 40) with a mean concentration of 1.85 +/- 0.98 ng ml-1 (mean +/-
      s.d., range 0.58-4.50 ng ml-1). No correlation with urinary pentachlorophenol
      (PCP) and no sex-related differences were found. The derivative may originate
      from the biotransformation of HCB stored in tissues and may be a useful maker of
      HCB metabolism in humans.

PMID- 1354976
TI  - Chromosomal aberrations and sister-chromatid exchange frequencies in workers
      occupationally exposed to textile dyes.
AB  - The peripheral lymphocytes of 11 male and seven female workers occupationally
      exposed to textile dyes were studied for cytogenetic change. A significant
      increase in the frequency of chromosomal aberrations and sister chromatid
      exchanges were recorded regardless of the duration of the workers' exposure to
      the dyes.

PMID- 1354977
TI  - Chronic low-dose exposure of sodium nitrite in VM-strain mice: central nervous
      system changes.
AB  - 1. There is suggestive evidence that nitrite may be a causative factor in
      cerebral glioma. 2. To test this hypothesis we selected the VM mouse strain,
      known for its susceptibility to spontaneous glioma formation, and exposed 300
      animals to 0.2% sodium nitrite in their drinking water. One hundred of this group
      were exposed both in utero and throughout their adult lives. The remaining 200
      animals received nitrite from the time of weaning. A further 200 mice were used
      as controls and received distilled water. 3. All animals were maintained until
      their natural death and were then subjected to autopsy and routine histological
      examination. 4. There was no excess of nervous system tumours in the experimental
      groups.

PMID- 1354978
TI  - Subacute toxicity of pentavalent antimony compounds in rats.
AB  - A subacute toxicity study of pentavalent antimony (Sb) compounds, sodium
      stibogluconate (SSG) and meglumine antimoniate (MA) was carried out in rats.
      Three groups of 10 rats each were treated with saline (control group), 300 mg Sb
      kg-1 d-1 or 900 mg Sb kg-1 d-1 of SSG for 30 d. A parallel study of similar type
      was conducted for MA. Compared with controls, drug-treated rats showed an
      impairment of feeding habits and retardation of weight gain (P less than 0.01)
      during the treatment period. In both SSG- and MA-treated rats there was a dose
      related reduction in haemoglobin concentration (P less than 0.001), and
      hematocrit (P less than 0.001). Red cell count was reduced in SSG-treated rats
      only. Both drugs, however, significantly raised the white cell count (P less than
      0.05). These changes were more pronounced with SSG them with MA. There was no
      change in MCV, MCH and MCHC. SSG, 900 mg Sb kg-1 d-1, significantly raised AST (P
      less than 0.005), ALT (P less than 0.01) and alkaline phosphatase activity (P
      less than 0.01). SSG-treated rats also had raised BUN (P less than 0.01) and
      creatinine (P less than 0.001), but no significant change in bilirubin levels. MA
      significantly raised AST (P less than 0.01), ALT (P less than 0.01), BUN (P less
      than 0.001) and serum creatinine levels (P less than 0.001), but had no
      appreciable effect on bilirubin and alkaline phosphatase levels. Both SSG and MA
      decreased blood glucose levels (P less than 0.01) and induced
      proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354979
TI  - Anterograde amnesia in triazolam overdose despite flumazenil treatment: a case
      report.
AB  - Anterograde amnesia, possibly accompanied by acute brain syndrome, is a potential
      side-effect of certain benzodiazepines, particularly triazolam. Flumazenil is a
      benzodiazepine antagonist that is highly effective in reversing the central
      nervous system effects of benzodiazepine overdose. We report a case of triazolam
      overdose resulting in anterograde amnesia after flumazenil administration had
      restored clear consciousness. The defect in memory may have been due to too
      little flumazenil being given or failure of memory consolidation affected by the
      character of triazolam during the induced lucent period. We feel that physicians
      should be aware of the potential occurrence of acute brain syndrome in patients
      with benzodiazepine overdose despite treatment with flumazenil.

PMID- 1354980
TI  - Indomethacin and protein binding of methotrexate.
AB  - Indomethacin, a non-steroidal anti-inflammatory drug is known to increase the
      efficacy and toxicity of methotrexate, the widely used anti-cancer drug in man.
      The mechanism for this interaction has not been clearly established. However,
      since these drugs bind with albumin, a possible displacement of methotrexate by
      indomethacin from albumin might explain this interaction. To investigate the
      possible interaction an in-vitro protein-binding displacement study was carried
      out in 17 normal volunteers and in two groups of eight cancer patients. One group
      of patients had active disease and the other was in complete clinical remission.
      Serum samples were obtained and protein levels estimated. The protein binding of
      methotrexate was measured alone and with indomethacin using equilibrium dialysis.
      Statistical analysis of results suggested that the binding of methotrexate is not
      influenced by indomethacin, confirming that methotrexate is not displaced by
      indomethacin.

PMID- 1354981
TI  - A case of affective psychosis after routine use of proprietary cold remedy
      containing phenylpropanolamine.

PMID- 1354982
TI  - Fatal intoxication due to the combined use of heroin and pyrithyldione.

PMID- 1354983
TI  - Pertussis toxin reverses prostaglandin E2- and somatostatin-induced inhibition of
      rat parietal cell H(+)-production.
AB  - In enzymatically dispersed enriched rat parietal cells we studied the effect of
      pertussis toxin on prostaglandin E2 (PGE2)- or somatostatin-induced inhibition of
      H(+)-production. Parietal cells were incubated in parallel in the absence
      (control cells) and presence of pertussis toxin (250 ng/ml; 4 h).
      [14C]Aminopyrine accumulation by both pertussis toxin-treated and control cells
      was used as an indirect measure of H(+)-production after stimulation with either
      histamine, forskolin or dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP)
      alone and in the presence of PGE2 (10(-9)-10(-7) M) or somatostatin (10(-9)-10(
      6) M). PGE2 inhibited histamine- and forskolin-stimulated [14C]aminopyrine
      accumulation but failed to alter the response to dbcAMP. Somatostatin was less
      effective and less potent than PGE2 in inhibiting stimulation by histamine or
      forskolin and reduced the response to dbcAMP. Pertussis toxin completely reversed
      inhibition by both PGE2 and somatostatin on histamine- and forskolin-stimulated
      H(+)-production but failed to affect inhibition by somatostatin of the response
      to dbcAMP. After incubation of crude control cell membranes with [32P]NAD+,
      pertussis toxin catalysed the incorporation of [32P]adenosine diphosphate (ADP)
      ribose into a membrane protein of molecular weight of 41,000, the known molecular
      weight of the inhibitory subunit of adenylate cyclase (Gi alpha). Pertussis toxin
      treatment of parietal cells prior to the preparation of crude membranes almost
      completely prevented subsequent pertussis toxin-catalysed [32P]ADP ribosylation
      of the 41,000 molecular weight protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354984
TI  - Contribution of the gamma-carboxyl group of Glu-43(beta) to the alkaline Bohr
      effect of hemoglobin A.
AB  - Glu-43(beta) of hemoglobin A exhibits a high degree of chemical reactivity around
      neutral pH for amidation with nucleophiles in the presence of carbodiimide. Such
      a reactivity is unusual for the side-chain carboxyl groups of proteins. In
      addition, the reactivity of Glu-43(beta) is also sensitive to the ligation state
      of the protein [Rao, M. J., & Acharya, A. S. (1991) J. Protein Chem. 10, 129
      138]. The influence of deoxygenation of hemoglobin A on the chemical reactivity
      of the gamma-carboxyl group of Glu-43(beta) has now been investigated as a
      function of pH (from 5.5 to 7.5). The chemical reactivity of Glu-43(beta) for
      amidation increases upon deoxygenation only when the modification reaction is
      carried out above pH 6.0. The pH-chemical reactivity profile of the amidation of
      hemoglobin A in the deoxy conformation reflects an apparent pKa of 7.0 for the
      gamma-carboxyl group of Glu-43(beta). This pKa is considerably higher than the
      pKa of 6.35 for the oxy conformation. The deoxy conformational transition
      mediated increase in the pKa of the gamma-carboxyl group of Glu-43(beta)
      implicates this carboxyl group as an alkaline Bohr group. The amidated derivative
      of hemoglobin A with 2 mol of glycine ethyl ester covalently bound to the protein
      was isolated by CM-cellulose chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354985
TI  - Prothrombin Salakta: substitution of glutamic acid-466 by alanine reduces the
      fibrinogen clotting activity and the esterase activity.
AB  - Structural studies on a hereditary abnormal prothrombin, prothrombin Salakta,
      have been performed to identify the difference responsible for its reduced
      fibrinogen clotting activity and its reduced esterase activity. Amino acid
      composition and sequence analyses of a peptide isolated from a lysylendopeptidase
      digest of the abnormal thrombin indicated that Glu-466 had been replaced by Ala.
      This amino acid substitution can result from a single nucleotide change in the
      codon for Glu-466 (GAG----GCG). The model building and the molecular dynamics
      simulation of thrombin Salakta suggest that the Glu-466----Ala substitution would
      change the proper conformation around the substrate binding site containing Trp
      468, which is a unique surface loop on the thrombin molecule. This is the
      experimental and theoretical evidence supporting the role of the surface loop
      containing Trp-468 for the proper conformation of the substrate binding site.

PMID- 1354986
TI  - Simultaneous determination of common benzodiazepines in blood using capillary gas
      chromatography.
AB  - Blood samples were extracted with n-butyl acetate, and the extracts analysed by
      capillary gas chromatography using DB-1 and DB-1701 capillary columns with
      electron-capture detection. The DB-1701 column was found to give better
      separation of different benzodiazepines (BZDs). Recoveries ranged from 79 to 98%.
      Detection limits ranged from 0.005 to 0.015 microM for triazolam and
      flunitrazepam, and from 0.02 to 0.1 microM for other BZDs. Data on accuracy and
      precision are given for diazepam, desmethyldiazepam, flunitrazepam and
      nitrazepam.

PMID- 1354987
TI  - Lithium chloride stimulates catecholamine synthesis and secretion in cultured
      bovine adrenal medullary cells.
AB  - We examined the effects of lithium treatment on the synthesis and secretion of
      catecholamines in cultured bovine adrenal medullary cells. The treatment of cells
      with lithium (0.5-4 mmol/L) for 7 days caused an increase in basal and carbachol
      stimulated synthesis of 14C-catecholamines from [14C]-tyrosine but not from [14C]
      DOPA. Lithium treatment (4 mmol/L, 7 days) increased the activity of tyrosine
      hydroxylase in the cells. Lithium treatment (2-4 mmol/L, 7 days) also enhanced
      the secretion of catecholamines caused by carbachol, although the carbachol
      induced influx of 45Ca2+ was reduced. Lithium (4 mmol/L, 7 days) potentiated the
      secretion of catecholamines evoked by the Ca2+ (1 mumol/L) from cells that were
      permeabilized by digitonin. The activity of protein kinase C in a soluble
      fraction was increased in lithium-treated cells (4 mmol/L, 7 days). These results
      demonstrate that lithium treatment increases the synthesis and secretion of
      catecholamines and the activity of protein kinase C in cultured adrenal medullary
      cells.

PMID- 1354988
TI  - Syndrome of inappropriate secretion of antidiuretic hormone associated with
      schizophrenia.

PMID- 1354989
TI  - Animal models for human diseases of the brain.

PMID- 1354990
TI  - Expression patterns of engrailed-like proteins in the chick embryo.
AB  - The protein products of both of the identified chick engrailed-like (En) genes,
      chick En-1 and chick En-2, are localized in cells of the developing brain,
      mandibular arch, spinal cord, dermatome, and ventral limb bud ectoderm, as
      demonstrated by labeling with the polyclonal antiserum alpha Enhb-1 developed by
      Davis et al. (Development 111:281-298, 1991). A subpopulation of cephalic neural
      crest cells is also En-protein-positive. The monoclonal antibody 4D9 recognizes
      the chick En-2 gene product exclusively (Patel et al.: Cell 58:955-968, 1989;
      Davis et al., 1991) and colocalizes with chick En-2 mRNA in the developing head
      region of the chick embryo as shown by in situ hybridization (Gardner et al.: J.
      Neurosci. Res. 21:426-437, 1988). In the present study we examine the pattern of
      alpha Enhb-1 and 4D9 localization throughout the chick embryo from the first
      appearance of antibody (Ab)-positive cells at stage 8 (Hamburger and Hamilton: J.
      Morphol. 88:49-92, 1951) through stage 28 (1-5.5 days). We compare the
      localization patterns of the two Abs to each other, as well as to the
      localization of the monoclonal Ab, HNK-1, which recognizes many neural crest
      cells, using double- and triple-label fluorescence immunohistochemistry. Most En
      protein-positive cells in the path of neural crest cell migration are not HNK-1
      positive. In detailed examination of alpha Enhb-1 and 4D9 localization, we find
      previously undetected patterns of En protein localization in the prechordal
      plate, hindbrain, myotome, ventral body-wall mesoderm, and extraembryonic
      membranes. Based upon these observations we propose: 1) that En expression in the
      mesoderm may be induced through interaction with En expressing cells in the
      neuroectoderm; 2) that En expression in the head mesenchyme is associated with
      somitomere 4; and 3) that En expression may be involved in epithelial-mesenchymal
      cell transformations.

PMID- 1354991
TI  - [Results of computerized tomography after Whipple operation of chronic
      pancreatitis].
AB  - 53 patients were controlled with CT after Whipple resection. The median age of
      the patients was 49 years, the median time after surgery nine years. Diagnostic
      criteria were the identification of the residual pancreas, signs of pancreatic
      atrophy and radiological signs of chronic pancreatitis. CT was performed with
      slice thickness of 4 mm and steps of 4 mm. The residual pancreas was visible in
      all 53 cases. Pancreatic atrophy was found in 26 cases, in four of these the
      residual pancreas was only 2 mm in size. Signs of chronic pancreatitis were found
      in 16 cases. By comparing preoperative and postoperative CT-scans, seven
      progresses of pancreatitis were detected. Signs of acute pancreatitis were not
      found in the 53 patients. Fatty liver degeneration was found in 7.5%. We found
      that CT is the most reliable technique to visualize the pancreas after Whipple
      resection. CT should be performed in all patients with clinical symptoms of an
      acute pancreatitis. CT should also be performed in patients with residual
      pancreas pseudocysts. There is no indication for CT in the routine examination of
      asymptomatic patients after Whipple resection.

PMID- 1354992
TI  - Recreational MDMA use in Sydney: a profile of 'Ecstacy' users and their
      experiences with the drug.
AB  - 'Ecstasy' (3,4-methylenedioxymethamphetamine or MDMA) is a recreational drug that
      is gaining popularity world wide. There is a paucity of research regarding the
      ways in which Ecstasy is used and the nature of its effects. A 'snowball' peer
      network technique was used to recruit 100 users who completed anonymous
      questionnaires. The research revealed that Ecstasy is primarily used by
      infrequent recreational drug users for 'fun' at dance parties and social
      gatherings. The primary reported effects of Ecstasy were a 'positive mood state'
      and feelings of intimacy and closeness to others. The secondary effects of
      Ecstasy were the stimulant effects of energy and activation, and the psychedelic
      effects of insight and perceptual and sensual enhancement. Ecstasy was reported
      to share the properties of both amphetamines and hallucinogens in the nature of
      its side effects and residual effects which were no more severe than those of the
      latter two classes of drug. It appeared Ecstasy was not conductive to regular and
      frequent use, because tolerance was reported to develop to the positive effects
      of Ecstasy, while negative effects increased with use. Although few problems
      associated with the recreational use of Ecstasy have surfaced to date, animal
      research has shown it to be neurotoxic to serotonergic nerve terminals. Caution
      must be observed until further research can determine the level of hazard in
      humans.

PMID- 1354993
TI  - Blood stem cell transplants come of age.
AB  - In this report we review meeting highlights. Clearly there has been substantial
      progress in the laboratory and clinic with regard to blood stem cells. Having
      proven that these transplants work, it is now time to investigate biologic
      features in greater detail. Also needed are randomized trials evaluating several
      of the issues we raise such as whether the better results of blood cell
      autotransplants are due to more effective treatment or subject selection and
      whether in vitro removal of tumor cells is necessary or effective.

PMID- 1354994
TI  - HLA-DR and DQ matching by DNA restriction fragment length polymorphism methods
      and the outcome of mixed lymphocyte reaction tests in unrelated bone marrow donor
      searches. The IMUST Study.
AB  - The use of DNA restriction fragment length polymorphism (DNA-RFLP) typing for HLA
      DR and DQ genes was assessed in 96 patients who were HLA-A,B and DR matched by
      serology with one or more potential unrelated marrow donors (UD). Two hundred
      recipient-donor pairs from 10 transplant centres in the UK were studied. DNA-RFLP
      revealed serological errors in HLA-DR typing and identified additional recipient
      donor mismatches. Of the 200 allegedly serologically matched pairs, 55 (28%) were
      mismatched for HLA-DR and/or DQ by DNA-RFLP typing. Of the 200 pairs, 68 (34%)
      mixed lymphocyte reactions (MLR) were negative and 132 (66%) positive. There was
      a significant correlation between DNA-RFLP defined mismatch and MLR positivity.
      However quantitative studies revealed no trend towards increasing MLR relative
      response index (RRI) with cumulative RFLP defined mismatch (i.e. for DR plus DQ
      compared with DR or DQ alone). RFLP matching for HLA-DR and DQ failed to predict
      a negative MLR. The RRI in the graft-versus-host direction was greater in RFLP
      matched pairs who carried HLA-DR4 than in matched pairs lacking DR4, suggesting
      that failure of RFLP to characterize DR4 subtypes was one reason why routine
      prediction of a negative MLR was not possible. Despite these limitations we have
      shown that DNA-RFLP is a reliable method for HLA-DR, DQ typing in routine UD
      searches in diverse clinical centres. By reducing the number of UD tested in MLR,
      RFLP typing can substantially reduce the work involved in donor selection.

PMID- 1354995
TI  - Growth retardation and depigmentation of hair after high-dose busulfan and
      congenic hematopoietic cell transplantation in mice.
AB  - Busulfan, a myeloablative but non-immunosuppressive alkylating agent, is used
      extensively in clinical bone marrow transplantation (BMT), but the effects of
      high-dose administration have not been previously evaluated in preclinical BMT
      settings with young murine recipients. We compared the survival and growth of
      C57BL/6 mice given graded single doses of busulfan (10-100 mg/kg) or total body
      irradiation (TBI; 900 cGy) at age 9 days and hematopoietic cell transplantation
      (HCT; transplantation of congenic bone marrow and spleen cells) 24 h later. The
      30-day survival was 87-100% in mice transplanted after 10-40 mg/kg busulfan and
      79% after TBI, but fell to 54% and 33%, respectively, after 80 mg/kg and 100
      mg/kg busulfan, suggesting that this latter dosage range represents the LD50 for
      single-dose busulfan in young C57BL/6 mice given stem cell rescue. The weights of
      10-week-old mice given HCT after lower doses of busulfan ranged from 87% of
      control at 10 mg/kg to 64-69% of control in mice conditioned with 35-65 mg/kg
      busulfan or TBI. Impairment of weight gain was most striking (approximately 50%
      of control) in mice transplanted after 80-100 mg/kg busulfan. Despite retardation
      of somatic growth, the brain weights of busulfan-conditioned mice remained at
      least 90% of control, and there were no obvious neuropathological alterations in
      the brains of these animals. All mice treated with at least 20 mg/kg busulfan or
      TBI lost hair by 3-4 weeks after transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354996
TI  - In situ hybridization histochemistry: a new method for processing material stored
      for several years.
AB  - We describe here a protocol developed to detect specific mRNAs by in situ
      hybridization using tissue sections that were not treated to inactivate RNase and
      were stored in cryoprotectant solution for several years. Brains from rats,
      monkeys and humans were sectioned at 50 microns and stored free floating in an
      ethylene glycol based cryoprotective solution at -20 degrees C. Rat brain
      sections were kept in cryoprotective solution for 3 days, 1 month and 2 months.
      Control sections were cut and mounted immediately on gelatin-coated slides and
      stored at -80 degrees C. Monkey brain sections were stored in cryoprotective
      solution for up to 5 years. Human sections were tested after storage for one
      year. Oligonucleotide probes that were complementary to human preproenkephalin
      mRNA (amino acid sequences 130-145), rat preproenkephalin mRNA (sequences 388
      435) and rat tyrosine hydroxylase mRNA (sequences 1441-1488) were labeled with
      35S-dATP and terminal deoxynucleotidyl transferase. To prevent possible RNase
      contamination from mounting the tissue sections onto gelatin coated slides, the
      in situ hybridization was performed in sterile culture dishes. Following each
      step, solutions were aspirated out of the dish. The amount of probe necessary for
      each section was 45 microliters (rat), 450 microliters (monkey), and 350
      microliters (human). Using this protocol, the detection of specific mRNAs in rat
      brain sections was more specific with less non-specific background as compared to
      control sections that were processed after they were mounted onto gelatin-coated
      sides. Excellent resolution was also obtained from monkey brain sections that
      were stored in cryoprotectant for up to 31 months and in human brain sections
      stored for 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1354997
TI  - Evidence for presynaptic dopamine mechanisms underlying amphetamine-conditioned
      locomotion.
AB  - Rats with a history of receiving (+)-amphetamine in a specific environment
      exhibit a conditioned psychomotor response when subsequently placed in that
      environment without drug treatment. Previous work has shown that while the
      unconditioned effects of amphetamine can be blocked by dopamine D1 or D2 receptor
      antagonists or with alpha-methyl-p-tyrosine, conditioned locomotion is not
      influenced by these treatments. In the present experiment, alpha-methyl-p
      tyrosine (50 mg/kg, s.c.) was given in conjunction with amphetamine (1.5 mg/kg,
      s.c.) for 8 days before testing for conditioned locomotion. alpha-Methyl-p
      tyrosine completely blocked amphetamine-induced locomotion but only attenuated
      amphetamine-conditioned locomotion. Reserpine (reduced over the 8 days from 2.5
      to 1.25 mg/kg, i.p.) did not block amphetamine-induced locomotion; indeed,
      potentiation of amphetamine-induced locomotor activity was observed on the last 3
      days of treatment. Reserpine treatment in conjunction with alpha-methyl-p
      tyrosine treatment blocked amphetamine-induced locomotion for the first 4 days
      only, with full recovery of amphetamine-induced unconditioned locomotion by the
      last treatment day. Reserpine alone had no effect on amphetamine-conditioned
      locomotion, but completely blocked amphetamine-conditioned locomotion when given
      with alpha-methyl-p-tyrosine. It is concluded that the alpha-methyl-p-tyrosine
      sensitive pool of dopamine mediates the immediate psychomotor effects of
      amphetamine, but that both the alpha-methyl-p-tyrosine- and reserpine-sensitive
      pools of dopamine are involved in the establishment of amphetamine-conditioned
      locomotion. In addition, the occurrence of amphetamine-conditioned locomotion is
      independent of the direct effects of amphetamine on locomotion.

PMID- 1354998
TI  - Interaction between thyrotropin-releasing hormone (TRH) and NMDA-receptor
      mediated responses in hypoglossal motoneurones.
AB  - The effect of thyrotropin-releasing hormone (TRH) on the responses to excitatory
      amino acids was investigated in hypoglossal motoneurones in an in vitro
      preparation of the brainstem from guinea pigs using current clamp and
      discontinuous single electrode voltage clamp (dSEVC). Bath application of 20-50
      microM TRH markedly potentiated the response to iontophoretically applied NMDA,
      whereas no potentiation of the response to glutamate, aspartate or quisqualic
      acid was seen. Voltage clamp experiments showed that TRH did not increase the
      current flowing through NMDA channels, thus a direct modulatory role of TRH on
      NMDA channels was not a likely explanation of the potentiation. Voltage clamp
      studies of the current-voltage relationship showed that the potentiation of the
      response to NMDA and lack of potentiation of the response to quisqualic acid was
      a result of an interaction between the actions of TRH and the amino acids on the
      electroresponsive profile of the membrane. Endogenous NMDA receptor activation
      was produced by tetanic stimulation of the reticular formation dorsolaterally to
      the hypoglossal nucleus, evoking large APV sensitive EPSPs in the presence of
      CNQX, a non-NMDA blocker. The amplitude and duration of these potentials were
      increased at more positive membrane potentials in response to TRH. It is
      concluded that TRH can act as a neuromodulator-potentiating the response to NMDA
      receptor activation-simply by changing the electroresponsive properties of the
      membrane.

PMID- 1354999
TI  - Amphetamine regulation of mesolimbic dopamine/cholecystokinin neurotransmission.
AB  - The effects of acute and repeated amphetamine administration on mesolimbic
      dopamine (DA) neurons was assessed by studying DA and cholecystokinin (CCK)
      release in the nucleus accumbens (Acc), as well as effects on mRNA genes
      regulating DA and CCK synthesis in ventral tegmental area (VTA) cells in rats.
      Amphetamine (1.5 mg/kg) markedly increased extracellular levels of DA in the
      medial Acc (assessed by in vivo microdialysis) in drug-naive animals, about twice
      the amount released in animals repeatedly administered the drug for the previous
      7 days (twice daily). CCK overflow was found to mirror the DA responses in that
      the very transient elevation of CCK monitored in drug-naive animals was
      attenuated in those with prior amphetamine use. The attenuation of both DA and
      CCK overflow in the medial Acc was found to be associated with a decrease in the
      number of CCK mRNA-positive VTA neurons (assessed by in situ hybridization
      histochemistry). Although the number of cells expressing CCK mRNA were decreased,
      the gene expression in those positive CCK and tyrosine hydroxylase mRNA cells in
      the VTA was significantly increased. The CCK mRNA neurons in the VTA were
      positively identified as those projecting to the medial Acc by the local
      perfusion of Fluoro-gold retrograde tracer via microdialysis probes located in
      the Acc.

PMID- 1355000
TI  - Regulation of excitatory amino acid release by N-methyl-D-aspartate receptors in
      rat striatum: in vivo microdialysis studies.
AB  - The microdialysis technique was utilized to study the effects of N-methyl-D
      aspartate (NMDA) receptor ligands on the in vivo release of endogenous glutamate
      (Glu) and aspartate (Asp) from the rat striatum. Addition of NMDA (250 and 500
      microM) to the dialysis perfusion solution resulted in a striking dose-dependent
      increase in extracellular concentrations of Glu and Asp in the striatum. The NMDA
      induced effects were reduced in a dose-related way by prior perfusion with 75
      microM dizocilpine (MK-801), a non-competitive NMDA receptor antagonist. MK-801,
      at 75 microM, produced no changes on basal levels of Glu and Asp. However, 100
      microM MK-801 did increase Glu and Asp extracellular concentrations. Local
      infusion with 500 microM D-serine, an agonist at the glycine site associated to
      the NMDA receptor, significantly increased basal level of Glu, but not Asp. Such
      D-serine-induced effects were reduced by 7-Cl-kynurenic acid (200 microM), a
      selective blocker of the glycine site present in the NMDA receptor. It is
      proposed that activation of NMDA receptors by endogenous Glu and Asp enhances the
      subsequent release of these excitatory amino acids in the striatum. Part of these
      NMDA receptors might be located presynaptically on cortico-striatal nerve
      endings. In addition, postsynaptic NMDA receptors present in the striatum may
      also indirectly modulate the release of Glu and Asp, through trans-synaptic
      mechanism.

PMID- 1355001
TI  - Adrenal hormone effects on hippocampal excitatory amino acid binding.
AB  - The influence of short-term adrenalectomy or corticosterone treatment on the
      binding of glutamate receptor subtypes in the rat hippocampus was explored using
      the technique of in vitro autoradiography. Analysis of NMDA, kainate and AMPA
      binding in the hippocampus was conducted on the brains of control,
      adrenalectomized, and adrenalectomized animals given corticosterone treatment. In
      addition, serum corticosterone levels were determined by RIA. No striking effects
      of acute adrenalectomy on the distribution or density of any glutamate receptor
      subtype were observed in the hippocampus. Adrenalectomy had a small but
      significant effect on kainate binding in the stratum lucidum and stratum radiatum
      of CA3 in the first experiment, but no effect in follow-up experiments. Short
      term treatment with stress levels of corticosterone had no effect on the binding
      of NMDA or kainate in any hippocampal subfield. However, a small effect of high
      doses of corticosterone (CORT) was observed on AMPA binding in one subregion.
      Although the hippocampus is a target for glucocorticoids and uses excitatory
      amino acids as a primary neurotransmitter, transient manipulation of adrenal
      hormone levels did not directly modulate excitatory amino acid receptor binding.

PMID- 1355002
TI  - Dopamine receptor antagonists increase markedly the quantity of retrograde
      transport of HRP in the rat masseteric motoneuron.
AB  - Horseradish peroxidase (HRP) was injected, bilaterally, into the rat masseter
      muscle, subsequent to an intramuscular or intraperitoneal injection of one of
      five dopamine antagonists (chlorpromazine and haloperidol as the D1 and D2
      receptor antagonist, SCH 23390 as the specific D1 receptor antagonist, sulpiride
      and domperidone as the specific D2 receptor antagonist). Control rats received an
      injection of a corresponding vehicle solution. After a survival period of 16 h,
      the brainstem was cut into 60 microns cryosections and processed with the TMB
      technique. The amount of retrogradely transported HRP was quantitatively measured
      in terms of the amount of HRP reaction product present in the motoneuron by the
      method which we have developed using an image processing system combined with a
      light microscope and a TV camera. Chlorpromazine, haloperidol, SCH 23390 and
      sulpiride significantly raised the quantity of retrograde transport of HRP. On
      the contrary, domperidone which can not penetrate the blood-brain barrier showed
      no significant change in the amount of the retrograde transport. In addition, an
      intravenous injection of chlorpromazine (8 mg/kg) was found to increase the
      amplitude of monosynaptic masseteric reflex EMG activity evoked by stimulations
      of the mesencephalic trigeminal nucleus. These results suggest that a possible
      regulatory system involving the dopamine receptor in the uptake and retrograde
      transport of HRP from axon terminals to cell bodies of the masseteric motoneuron
      exists in higher order neurons which make synaptic contact with the motoneuron.

PMID- 1355003
TI  - Calcium-dependent release of glutamate from human cerebral cortex.
AB  - The release of the excitatory amino acids glutamate and aspartate from human
      neocortex was investigated in vitro by utilizing brain tissue removed during
      anterior temporal lobectomies for tumor or epilepsy. Depolarization (50 mM K+)
      increased the glutamate release to 291% of control (809 pmol/mg/min) during
      blocked synaptic transmission and to 669% (1859 pmol/mg/min) when synaptic
      transmission was not blocked. Aspartate release increased to 141% (326
      pmol/mg/min) and 178% (412 pmol/mg/min) respectively. The difference between
      release with and without blocked synaptic transmission was statistically
      significant only for glutamate (P less than 0.01). These data provides evidence
      for a Ca(2+)-dependent release of glutamate, supporting a possible role of this
      amino acid as a neurotransmitter in human neocortex.

PMID- 1355005
TI  - Somatostatin receptors increase in the olfactory bulb of developing pups after
      perinatal exposure to cocaine.
AB  - The effects of chronic prenatal and/or postnatal exposure to cocaine on
      somatostatin concentration and receptors were studied in the olfactory bulbs of
      rat pups at birth and at 15 days old. Wistar rats were injected subcutaneously
      with single daily doses of 40 mg cocaine hydrochloride/kg from days 7 to 19 of
      gestation, from day 7 of gestation to day 15 postpartum or from parturation to
      day 15 postpartum. Fetal exposure to cocaine decreased SS concentrations in the
      olfactory bulb of the newborn pups while prenatal-plus-postnatal exposure
      increased this parameter. Administration of cocaine only during lactation did not
      induce any change. Exposure during gestation or during nursing induced an
      increase in the total number of somatostatin receptors and a decrease in the
      affinity constant in the olfactory bulb of newborn and 15-day-old pups. These
      results suggest that the development of somatostatin receptors in the olfactory
      bulb can be altered by prenatal and/or nursing period exposure to cocaine.

PMID- 1355004
TI  - Inhibition of energy metabolism by 3-nitropropionic acid activates ATP-sensitive
      potassium channels.
AB  - 3-Nitropropionic acid (1 mM), which inhibits succinate dehydrogenase activity and
      reduces cellular energy, produces in the pyramidal cell layer of the hippocampal
      region CA1 a hyperpolarization for variable lengths of time before evoking an
      irreversible depolarization. Hyperpolarization is caused by an increased
      potassium conductance that is attenuated by glibenclamide (1-10 microM), a
      selective antagonist of ATP-sensitive potassium channels; in contrast, diazoxide
      (0.5 mM), an agonist at this channel, induces a hyperpolarization in CA1 neurons
      of rat hippocampal slices. The transient hyperpolarization after prolonged (ca. 1
      h) application of 3-NPA is followed by a depolarization that is incompletely
      reversed by brief application of the glutamate antagonists (D-2-amino-5
      phosphonopentanoic acid (APV), 6,7-dichloroquinoxaline-2,3-dione (CNQX), 3-(+/-)
      2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), 7-chloro-kynurenic acid
      (7Cl-KYN)). Early application of glibenclamide (within the initial 5 min) blocked
      or reduced hyperpolarization and accelerated the depolarization. These data
      suggest that metabolic inhibition by 3-NPA initially activates ATP-sensitive
      potassium channels. Events other than activation of glutamate receptors
      participate in the final depolarization resulting from uncoupling of oxidative
      phosphorylation.

PMID- 1355006
TI  - American Cancer Society, National Conference on Colorectal Cancer. New Orleans,
      Louisiana, March 20-22, 1991.

PMID- 1355007
TI  - Cellular events accompanying regression of skin recurrences of breast carcinomas
      treated with intralesional injections of natural interferons alpha and gamma.
AB  - Cutaneous recurrences of breast carcinomas were treated with 10 i.l. injections
      of nIFNs alpha and gamma delivered in combination (7 lesions) or singly (11 with
      nIFN-alpha, one with nIFN-gamma). Histologically confirmed complete regressions
      occurred in 5 of 7 lesions treated with nIFN-alpha/nIFN-gamma and in 5 of 11
      recurrences injected with nIFN-alpha alone. In all cases specimens were obtained
      before and after therapy. In addition, in some cases (4 treated with nIFN
      alpha/nIFN-gamma, 2 with nIFN-alpha, one with nIFN-gamma) multiple recurrences
      were injected simultaneously and were excised 24 h after 1, 3, and 10 injections
      and 21 days after completion of therapy. The main findings observed in the
      treated lesions undergoing complete and partial regressions included: (a)
      inhibition of mitotic activity and up-regulation of antigenic expression (mammary
      epithelial membrane antigen, intercellular adhesion molecule 1, HLA-DR) by the
      carcinoma cells; (b) activation of macrophages and dendrocytes with marked
      expression of HLA-DR and HLA-A,B,C; (c) infiltration of the dermis and tumors by
      activated T-lymphocytes (CD3+, CD4+, CD8+); (d) questionable participation by B
      lymphocytes and natural killer cells; (e) activation of endothelium with
      enhancement of antigenic expression (intercellular adhesion molecule 1, HLA-DR),
      procoagulant activity, and vascular permeability. The responses elicited by nIFN
      alpha/nIFN-gamma were greater than those caused by either IFN used alone. It
      appears that in these patients the IFNs exerted an antiproliferative action and
      potentiated a cell-mediated immunological response liminally present in the
      neoplastic tissues prior to therapy.

PMID- 1355008
TI  - Reversal of multidrug resistance by two novel indole derivatives.
AB  - Two new fused indoles were found to overcome multidrug resistance in P388/Adr
      cells in vitro. These agents potentiated the cytotoxicity of the antitumor drugs
      Adriamycin, vinblastine, and vincristine in multidrug-resistant cells with no
      effect on drug-sensitive parent P388 cells. They significantly increased the ATP
      dependent accumulation of [3H]-vinblastine and inhibited efflux of the labeled
      drug from resistant cells. These compounds also inhibited photoaffinity labeling
      of P-glycoprotein by [3H]azidopine in P388/Adr cells and membranes isolated from
      these cells. In addition, the calcium antagonist activity of these compounds was
      very weak compared with that of verapamil. These data suggest that the compounds
      reported here may specifically overcome multidrug resistance without the serious
      hypotensive effects associated with calcium antagonists and that this activity
      may be independent of their ability to block calcium transport.

PMID- 1355009
TI  - Differential susceptibility of cultured human melanoma cell lines to enhancement
      by retinoic acid of intercellular adhesion molecule 1 expression.
AB  - The potential role of intercellular adhesion molecule 1 (ICAM-1) in the biology
      of human melanoma cells has stimulated interest in the characterization of its
      modulation. The present study has shown that the differentiating agent retinoic
      acid (RA) up-regulates ICAM-1 expression by melanoma cells in a dose- and time
      dependent fashion. The enhancement of ICAM-1 cell surface expression is
      paralleled by an increase in ICAM-1 mRNA. Therefore, ICAM-1 represents an
      additional gene which may be transcriptionally regulated by RA. The five melanoma
      cell lines tested displayed a differential susceptibility to the modulation of
      ICAM-1 expression by RA, since the cell line MeWo did not change in its ICAM-1
      expression following incubation with RA. Nevertheless, RA-insensitive as well as
      RA-sensitive melanoma cell lines displayed a higher increase in ICAM-1 expression
      following incubation with RA and cytokines than following incubation with each of
      them. Analysis of the distribution in the melanoma cell lines of retinoic acid
      receptors (RARs) showed a relationship between susceptibility to a RA-mediated
      increase of ICAM-1 expression and RAR beta expression, suggesting that the latter
      receptor may play a role in the phenomenon. RAR alpha and RAR gamma were present
      in RA-sensitive and -insensitive melanoma cell lines, suggesting that they play a
      role in the enhancement by RA of cytokine-mediated up-regulation of ICAM-1
      expression. The melanoma cell lines we have described may represent a useful
      system for investigating the role of RAR in the regulation of gene expression and
      the mechanism(s) which underlie this effect.

PMID- 1355011
TI  - Immunoscintigraphic localization of renal tumours in an extracorporeal perfusion
      model with a monoclonal antibody against gamma-glutamyltransferase.
AB  - Monoclonal antibody 138H11 against human gamma-glutamyltransferase has been shown
      to react immunohistochemically with 98% of all tested clear-cell type and
      chromophilic renal cell carcinomas, but not with renal chromophobic carcinomas,
      Duct-Bellini carcinomas or oncocytomas. In normal kidney the target epitopes of
      mAb 138H11 are located in the luminal brush-border membrane of proximal tubule
      cells, whereas in renal carcinomas the epitopes are found surrounding the whole
      tumour cells. These results form the basis of the present immunoscintigraphic
      study designed to evaluate mAb 138H11 in an extracorporeal perfusion model.
      Immediately after nephrectomy, human tumour-bearing kidneys were perfused with
      99mTc-labelled mAb 138H11 in Euro-Collins solution. High specific uptake in 4/4
      renal clear cell carcinomas could be demonstrated by planar immunoscintigraphy
      and single-photon-emission computed tomography, "regions of interest"
      investigation and immunohistochemistry. In contrast, a perfused oncocytoma showed
      up as an unlabelled lesion. The results indicate a possible use for mAb 138H11 in
      immunoscintigraphy or even therapy, provided high tumour uptake can be confirmed
      in patients.

PMID- 1355012
TI  - Left ventricular geometry in Takayasu arteritis complicated by severe aortic
      regurgitation.
AB  - Although it has been reported that the aortic regurgitation (AR) of patients with
      Takayasu arteritis is due to dilatation of the aortic ring, the geometry of the
      left ventricle (LV) has not been described. We compared the cardiac findings in
      patients with Takayasu arteritis (TA) and severe AR with those of patients having
      severe AR of other origins. Echocardiographically, wall thickness (WT) and the
      concentric hypertrophic ratio (WT/WT + left ventricular end-diastolic dimension)
      were greater in patients with TA. It is concluded that the LV of the TA patients
      revealed concentric hypertrophy even when AR was severe.

PMID- 1355010
TI  - Tissue localization of methotrexate-monoclonal-IgM immunoconjugates: anti-SSEA-1
      and MOPC 104E in mouse teratocarcinomas and normal tissues.
AB  - Methotrexate (MTX) was coupled to the tumor-targeting monoclonal IgM, anti-SSEA-1
      and the non-targeting myeloma IgM, MOPC 104E. At 24-h intervals following
      injection, drug deposition in MH-15 teratocarcinomas and in several normal
      tissues was followed by immunoperoxidase microscopy using the M16 monoclonal
      antibody to MTX. MTX-anti-SSEA-1 was deposited on the surface and in the interior
      of living tumor cells 24 h after injection; at 48 h and after, only low-level
      binding to necrotic tissue was found. There was no significant gradation in
      staining from the outside to the interior of the tumors. In tumors, the control
      MOPC 104E immunoconjugate was detectable only in necrotic tissue. Binding to SSEA
      1-expressing normal tissues was undetectable, except for pericryptal fibroblasts
      in the small intestine. No significant pathology was found in normal tissues that
      are SSEA-1 positive. High levels of the immunoconjugate were detected in the
      liver, where MTX was found predominantly in Kupffer cells and possibly in
      hepatocytes; again, no significant morphological changes were associated with
      this retention. Thus tumor-associated antigens can be suitable targets for
      antibody-drug conjugates even when present in normal tissues and in large
      quantities, provided that the antigens in normal tissues are inaccessible.
      Moreover, deposition in viable tumor tissue can be assessed using monoclonal
      antibodies to methotrexate.

PMID- 1355013
TI  - Involvement of the Th1 subset of CD4+ T cells in acquired immunity to mouse
      infection with Trypanosoma equiperdum.
AB  - Heat- or merthiolate-inactivated Trypanosoma equiperdum was administered to
      recipient mice that were subsequently challenged with viable inocula of the same
      stabilate. Only mice inoculated with merthiolate-killed parasites were completely
      protected from a challenge inoculum of 10(3) trypanosomes, an effect that was
      abolished by prior immunosuppression of mice. Immune sera from protected animals
      contained high levels of interferon (IFN)-gamma and specific IgG2a antibodies.
      Spleen cells from these mice produced high amounts of interleukin (IL)-2 and IFN
      gamma in vitro in response to specific antigen or concanavalin A, whereas
      splenocytes from mice receiving heat-killed parasites produced high amounts of IL
      6. In contrast, the production of tumor necrosis factor (TNF)-alpha and colony
      stimulating activity (CSA) was not significantly different in mice receiving
      either killed parasite preparation. The protection in immunized mice was
      associated with the detection of strong delayed-type hypersensitivity (DTH) to T.
      equiperdum antigens, an effect that could be adoptively transferred onto naive
      recipients by specifically immune CD4+ lymphocytes. These results suggest that
      the development of protective immunity in mice to T. equiperdum by our
      immunization protocol may involve the activity of helper/DTH T cells,
      particularly those of the Th1 subset.

PMID- 1355014
TI  - Regulation of the expression of leukocyte function-associated antigen-1 (LFA-1)
      and intercellular adhesion molecule-1 (ICAM-1) on a human eosinophilic leukemia
      cell line EoL-3.
AB  - The effects of several cytokines and phorbol myristate acetate (PMA) on LFA-1 and
      ICAM-1 expression on a human eosinophilic leukemia cell line, EoL-3, were
      investigated and compared with those of a human monocytic leukemia cell line,
      U937. EoL-3 cells expressed large amounts of LFA-1 and small amounts of ICAM-1,
      and their expression was regulated similarly in EoL-3 cells and U937 cells.
      Interferon-gamma (IFN-gamma) enhanced ICAM-1 expression but not LFA-1 expression,
      and PMA augmented both LFA-1 and ICAM-1 expression. IFN-gamma and PMA showed an
      additive effect on ICAM-1 expression. These results collectively suggest that
      expression of LFA-1 and ICAM-1 is regulated differently and that IFN-gamma and
      PMA regulate the expression through different mechanisms. PMA but not IFN-gamma
      induced homotypic adhesion of EoL-3 and U937 cells, suggesting that PMA but not
      IFN-gamma activated the adhesive function of these cells. Staurosporin, an
      inhibitor of protein kinases (PKs), partly suppressed IFN-gamma- and PMA
      augmented expression of ICAM-1 on EoL-3 and U937 cells, but did not affect PMA
      augmented LFA-1 expression, suggesting that staurosporin-sensitive PKs are
      involved in IFN-gamma- and PMA-augmented ICAM-1 expression but not in PMA
      augmented LFA-1 expression. The role of protein kinase C (PK-C) in these
      mechanisms was not revealed because a PK-C inhibitor, H-7, did not show any
      definitive effect on IFN-gamma- and PMA-induced expression of LFA-1 and ICAM-1.
      Moreover, cyclic AMP (cAMP)- and cGMP-dependent pathways were not shown to be
      involved in the augmentation of the expression of these molecules.

PMID- 1355015
TI  - Developmental expression of the proenkephalin and prosomatostatin genes in
      cultured cortical and cerebellar astrocytes.
AB  - Astrocytes were prepared from rats of 4 ages, embryonic day 20, postnatal days 3
      and 8, and adult, in order to study the developmental time course of expression
      of enkephalin and somatostatin (SS). Glial fibrillary acidic protein (GFAP)
      content was constant in both cortical and cerebellar astrocytes prepared from all
      ages. SS mRNA and peptide decreased over this developmental time course in
      cerebellar astrocytes; the time course of changes in SS mRNA paralleled that for
      rat cerebellum. Proenkephalin (PE) mRNA increased about 3-fold in cerebellar
      astrocytes from embryonic day 20 to adult but remained constant in cortical
      astrocytes; in contrast, PE mRNA showed a 10- to 12-fold increase in rat
      cerebellum and cortex developmentally. For both cerebellar and cortical
      astrocytes, free met-enkephalin decreased from embryonic day 20 to adult, whereas
      total met-enkephalin (measured following trypsin-carboxypeptidase B digestion of
      the extracts) increased. These results suggest (1) that there is a developmental
      regulation of the expression of both enkephalin and SS peptides in astrocytes,
      and (2) that the regulation occurs at the level of transcription for SS but at
      the level of precursor processing for PE. Possible trophic functions for
      astrocyte-derived peptides early in CNS development are discussed.

PMID- 1355016
TI  - N-methyl-D-aspartate effects on the growth, morphology and cytoskeleton of
      individual neurons in vitro.
AB  - Short-term (up to 5 h post-plating) cerebellar granule cell cultures were
      prepared from the week-old rat and maintained in a micro-incubator during time
      lapse video microscopy to examine normal and N-methyl-D-aspartate (NMDA)-evoked
      neurite extension. In untreated cultures growth of neurites was stochastic but
      proceeded at an average rate of 12.0 +/- 1.4 microns/h. Growth cone morphology
      was variable. The classical filopodia and lamellipodia possessing tips were
      motile or non-motile, while those processes ending in a club shape were rarely
      seen to extend. Individual growth cones passed through several different
      morphologies during growth. New processes extended more rapidly (13.0 +/- 1.7
      microns/h) than those already present (9.0 +/- 0.5 microns/h). Addition of the
      NMDA receptor antagonist, aminophosphonovalerate (APV), caused a marked
      retraction of pre-existing processes. Stimulation of the receptor with 50 microM
      NMDA caused a marked increase in growth rate compared to controls (15.0 microns/h
      and 1.7 microns/h, respectively). When the presence of actin-rich structures was
      examined using rhodamine-phalloidin labelling it was found that NMDA increased
      the proportion of neuronal processes that possessed a growth cone by 28%.
      Conversely, inhibition of NMDA receptor activity with APV reduced the formation
      of lamellipodia from neuronal cell bodies.

PMID- 1355017
TI  - Developmental expression of somatostatin receptors in the rat retina.
AB  - The ontogeny of somatostatin receptor binding was studied in developing rat
      retina using the iodinated derivative of the somatostatin analog, SMS 204-090.
      Specific binding of the ligand was seen as early embryonic day (E) 15 in the
      region of the inner neuroblastic layer. At E19 binding was localized to the
      ganglion cell and developing inner plexiform layers. At postnatal day (P) 2,
      there was diminished binding on autoradiography in this region. At P11, binding
      was more intense in the inner plexiform layer, and there was discernible binding
      in the outer plexiform layer. In the adult retina, the binding was seen clearly
      in two distinct bands corresponding to the inner plexiform layer and the outer
      plexiform layer. There was a single saturable binding site with the dissociation
      constant (Kd) of 0.25 +/- 0.04 nM. Binding sites were fairly constant throughout
      development except for a significant decline during the first postnatal week
      (Bmax = 1.8). These results demonstrate the early appearance of somatostatin
      receptors in the rat retina with high levels present embryologically followed by
      a brief decline in the early postnatal period with a return to high levels by
      synapse formation (P11). These receptor data parallel previous reports of the
      appearance of the somatostatin mRNA and peptide in rat retina.

PMID- 1355020
TI  - Symposium on diversity of membrane cation transport in vertebrate red blood
      cells. An overview.

PMID- 1355019
TI  - Effects of acute febrile infectious diseases on the oral pharmacokinetics and
      effects of nitrendipine enantiomers and of bisoprolol.
AB  - In 2 longitudinal studies with 10 patients each, the stereoselective
      pharmacokinetics of nitrendipine and the pharmacokinetics of racemic (rac)
      bisoprolol (both 20mg orally) were investigated during acute febrile infectious
      diseases and at least 6 weeks later in the healthy state. The area under the
      plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) of rac
      nitrendipine were increased in the infectious state by 89% [95% confidence
      interval (CI): 24 to 187%] and 95% (95% CI: 22 to 209%), respectively. Similar
      increases were observed for both S- and R-nitrendipine. Nitrendipine exhibited
      stereoselective pharmacokinetics in both the healthy state and the infectious
      state, but the mean ratios of S:R AUC values [healthy: 1.79 (95% CI: 1.36 to
      2.11); infectious: 1.87 (95% CI: 1.62 to 2.11)] were not different. The
      elimination half-life, protein binding and haemodynamic effects of nitrendipine
      also did not differ between the infectious and the healthy state. The mechanism
      for the disease effects may be related to suppression of hepatic cytochrome P450
      activity by mediators of inflammatory reactions. On the other hand, none of the
      pharmacokinetic parameters, including nonrenal clearance, of rac-bisoprolol was
      changed during febrile infectious disease, indicating specificity in the effects
      of acute febrile disease on oxidative drug metabolism.

PMID- 1355018
TI  - Pharmacokinetic optimisation of antiemetic therapy.
AB  - Antiemetic drugs are used to treat nausea and vomiting due to a variety of causes
      and have a wide range of pharmacological properties. The choice of drug will,
      therefore, depend in part on the condition being treated. The drugs can be
      classified as dopamine antagonists (including phenothiazines and
      nonphenothiazines), corticosteroids, cannabinoids, benzodiazepines, serotonin
      antagonists, antihistamines and anticholinergics. There is very little evidence
      of a relationship between plasma drug concentrations and either their efficacy or
      the incidence of adverse effects with most antiemetic drugs. With drugs for which
      concentration-effect studies have been performed, e.g. the benzodiazepines and
      antihistamines, the effects monitored have not been directly relevant to their
      use as antiemetics. Antiemetics are used widely, for example, in cancer
      chemotherapy. Nonetheless, apart from metoclopramide, little work has been done
      on the influence of indicators of systemic disease on the pharmacokinetics of
      antiemetic drugs.

PMID- 1355021
TI  - Regulation of Na+/H+ exchange and pH in erythrocytes of fish.
AB  - 1. The function of trout RBC Na+/H+ antiport is unrelated to cell volume or cell
      pH regulation. Its role is to improve oxygen transport capacity when the supply
      of oxygen becomes limited. 2. Antiport activation, mediated by cAMP, promotes
      complex changes in blood pH which have been analyzed in vivo and in vitro. 3. The
      regulation of antiport (activation, desensitization, control by molecular oxygen
      and by a newly discovered cytosolic protein, arrestin) is presented. 4. Molecular
      cloning of the antiport shows that two typical site motifs of phosphorylation by
      cAMP-dependent protein kinase are localized on the cytoplasmic region.

PMID- 1355022
TI  - Cell volume and pH regulation by the Amphiuma red blood cell: a model for hypoxia
      induced cell injury.
AB  - The Amphiuma red blood cell is one of the model systems employed early in the
      study of vertebrate cell volume regulation. Following both cell swelling and
      shrinkage the Amphiuma red blood cell demonstrates volume regulation to virtual
      completion in 90-120 min. When swollen the Amphiuma red blood cell loses K, Cl
      and osmotically obliged water, while following shrinkage volume regulation is the
      result of Na, Cl and therefore water uptake. The main contribution of the
      Amphiuma red cell as a model is that it was the first cell in which volume
      regulation was demonstrated to be electroneutral and more specifically that K/H
      and Na/H exchangers were responsible for regulation following cell swelling and
      shrinkage, respectively. Additionally, the Amphiuma red blood cell K/H and Na/H
      exchangers have been demonstrated to function in a pH regulatory capacity. The
      latter observation in turn led to the demonstration of the mutually exclusive and
      contradictory nature of volume and pH regulation predicted upon Na/H exchanger
      activity. These observations prompted our recent investigations of the Na/H
      exchanger as a contributor to hypoxia-induced cell damage, using the rabbit heart
      as a model. These studies illustrated that Na, and Ca imbalances characteristic
      of hypoxia-induced cell damage are ultimately referable to the Na/H exchanger's
      function in a pH regulatory capacity, which contributes fundamentally to cell
      volume and Ca derangement and ultimately cell injury.

PMID- 1355023
TI  - Diversities of transport of sodium in rodent red cells.
AB  - 1. Na-K pumps of rodent red cells reveal variations among species in terms of
      kinetic properties such as ouabain sensitivity, Na/K coupling and temperature
      sensitivity and variations within an individual organism related to such
      physiological challenges as K deficiency, calorie deficiency and seasonal changes
      in temperature. 2. Passive Na entry among rodents collectively occurs through the
      same routes as in red cells of other mammals, but red cells of hamsters, rats and
      thirteen-lined ground squirrels lack or are deficient in an amiloride-sensitive,
      shrinkage-activated Na-H exchange. 3. In guinea-pig this pathway appears to be
      both activated and uncoupled by cooling from 37 to 20 degrees C. 4. Red cells of
      rodents in general and hamsters in particular are rich in a Na-Mg exchange
      pathway. In hamsters, this appears to be the only amiloride-sensitive pathway in
      simple media. 5. In hamster cells, Na entry through the amiloride-sensitive Mg
      activated pathway exhibits the same kinetics as previously shown for Na
      activation of Mg extrusion.

PMID- 1355024
TI  - Volume-activated cation transport in dog red cells: detection and transduction of
      the volume stimulus.
AB  - 1. Carnivore red cells lose their Na/K pump capability as they develop from
      erythroblasts to reticulocytes to mature cells. They defend their fluid volume by
      utilizing the Ca/Na exchanger as a Na extrusion pump, the energy for which is
      ultimately derived from active Ca transport. 2. Swelling-induced [K-Cl]
      cotransport and shrinkage-induced Na/H exchange are regulated in a coordinated
      fashion in dog red cells. Circumstantial evidence points to a regulatory protein
      kinase-phosphatase system. 3. Dog red cells detect changes in their fluid volume,
      not by virtue of membrane distortion, but by alterations in the concentrations of
      cytoplasmic macromolecules induced by swelling or shrinkage.

PMID- 1355025
TI  - Ferret red cells: Na/Ca exchange and Na-K-Cl cotransport.
AB  - The primary pathway for K influx in ferret red cells is the Na-K-Cl cotransporter
      and the primary pathway for Ca influx is the Na/Ca exchanger. This makes ferret
      red cells favorable models for the study of these two transport systems. The
      evidence that Na/Ca exchange is of primary importance for steady state cell
      volume regulation and the Na-K-Cl cotransport has a minor role is presented. The
      approaches to, and results of, the determination of the stoichiometry, of the
      mechanism, and of the regulation by ATP and Mg, for Na/Ca exchange is contrasted
      with that taken for Na-K-Cl cotransport.

PMID- 1355027
TI  - Metabolic profiles of spinal motoneurons in fish as established by quantitative
      enzyme histochemistry.

PMID- 1355026
TI  - Ion transport in sheep red blood cells.
AB  - There is a polymorphism (HK/LK or high potassium/low potassium) of the cation
      concentrations in sheep red cells which also affects the cation transport
      pathways in these cells. The current status of understanding of two of these
      pathways in LK red cells, the Na/K pump and the K-Cl cotransporter, is summarized
      here. Recent results are presented on stimulation of the Na/K pump by insulin
      like growth factor, and on the transduction mechanism by which changes in cell
      volume modulate the K-Cl cotransporter.

PMID- 1355028
TI  - Gill (Na+ +K+)-ATPase involvement and regulation during salmonid adaptation to
      salt water.
AB  - 1. The involvement of gill (Na+ +K+)-ATPase in salmonid adaptation to salt water
      (SW) is discussed. 2. Gill (Na+ +K+)-ATPase increase during SW adaptation is
      mainly related to the increased number and complexity of chloride cells deputed
      to salt extrusion. 3. The temporal relationships between serum peaks of thyroid
      hormones, cortisol, growth hormone, prolactin and gill (Na+ +K+)-ATPase rise
      during salmonid smoltification, suggest a hormonal involvement in the enzyme
      stimulation and thus in the acquirement of SW tolerance. 4. Literature on gill
      (Na+ +K+)-ATPase response to hormonal treatment is reviewed. The effects produced
      on gill (Na+ +K+)-ATPase and chloride cells by exogenous hormones point out a
      complex inter-relationship between the hormones considered. The mechanisms
      involved in hormonal regulation of the enzyme remain a matter of debate.

PMID- 1355029
TI  - Hemosomegenesis and hemoglobin biosynthesis in vertebrates.
AB  - 1. Ultrastructural observations on maturing rabbit embryo erythroid cells led to
      the finding of hemoglobinized organelles distinguishable from mitochondria due to
      their highly dense matrix, two or three longitudinally arranged double lamellae,
      and smaller diameters. Intraorganellar 50-60 A particles identical to those
      contained in the hemoglobinized cytoplasm were found. 2. Their hemoglobin (Hb)
      content was demonstrated by electrophoresis of the concentrated supernatant from
      the isolated, washed, and osmotically lysed organellar fraction. We have proposed
      that these organelles are the sites for heme integration into the globin (G)
      polypeptide chains and subunits assembly. The term hemosome has been suggested
      for such entities. 3. This hypothesis has been sustained by several analytical
      and experimental works based on the postulation that hemosomes should be found at
      higher frequencies where the Hb biosynthesis rate is more intensive, or where the
      induction of this biosynthesis is always dependent on the formation of hemosomes.
      4. Maturing erythroid cells of the circulating embryo blood contain hemosomes in
      higher frequency than in liver erythroid cells, coinciding with the higher Hb
      biosynthesis rate in peripheral blood than in the liver. In bleeding anemia, the
      decay of Hb concentration parallels the reduction of the mean number of hemosomes
      per reticulocyte, in comparison with normal reticulocytes. 5. In HeLa cells and
      epithelial cultured cells induced to synthesize Hb, it was shown that this
      biosynthesis is ever concomitant with the formation of hemosomes and depends on
      the presence of erythropoietin, as occurs in erythroid cells. 6. Studies on
      hemosomegenesis and Hb biosynthesis experimentally effected in epithelial
      cultured cells, allowed the interpretation of the sequence of events leading to
      hemosome formation in maturing erythroid cells. Simultaneously with iron uptake,
      mitochondria differentiate to lamellated bodies and, successively, expansions
      rise for ferruginous compounds and G polypeptides gathering, followed by
      prehemosome vesicles formation, which condense and change to prohemosomes that
      afterwards evolve to hemosomes. 7. These dynamics, and organellar Hb have been
      detected in immature erythrocytes of mammalians, including humans, avians,
      reptilians, amphibians and representative fish specimens. It appears that these
      events occur in the erythrocytary maturation of all vertebrate classes.

PMID- 1355030
TI  - Prolactin and the onset of mammary extraction of plasma triacylglycerols during
      lactogenesis in the goat.
AB  - 1. In untreated goats, the onset of mammary extraction of circulating
      triacylglycerols (TG) at parturition occurred shortly after the peak of prolactin
      concentration in circulating plasma. Suppressing this peak of systemic prolactin,
      by acutely treating with bromocriptine, delayed the onset of mammary extraction
      of TG and secretion of long-chain TG fatty acids. 2. Regular unilateral removal
      of secretion pre-partum, which brought about an early local onset of TG
      extraction and secretion of long-chain TG fatty acids in this treated half of the
      udder, was not associated with an increased local concentration of prolactin in
      secretion in this gland.

PMID- 1355032
TI  - Determination of transepithelial (mucosal and serosal) electrical potentials in
      toad skin. Action of chemical agents.
AB  - 1. Potential differences across the mucosal or outer, and the serosal or inner,
      membranes of the toad skin (M and S) were recorded separately. Total potential
      difference across the skin (T) and the short-circuit current (SCC) were recorded
      by means of the classical Ussing method. 2. The independent determination of the
      M and the S is of importance in the elucidation of the mechanism of action of
      agents which alter ion fluxes across the skin. 3. The percentage values of the M
      and the S obtained in toad skins during the summer were similar to the percentage
      values obtained by microelectrode impalement of cells. 4. Angiotensin II (AII)
      and antidiuretic hormone (ADH) increased T with a notable rise in M and a slight
      increase in S. These agents act mainly by increasing mucosal membrane
      permeability to Na+ since M is principally affected. 5. Amiloride and ouabain
      reversed M, decreased T and increased S above T. The reversal of M might be
      explained by the flow of a cation to the mucosal aspect or of an anion to the
      cell interior. 6. These results show that the effects of several agents on the
      toad skin potential may be analysed independently across the mucosal and serosal
      membranes and reflect the behaviour of the entire tissue rather than of a single
      cell.

PMID- 1355031
TI  - Comparison of the subcellular distribution of alveolar surfactant in two
      mammalian species of similar body weight: cat and rabbit.
AB  - 1. We studied the total amount and subcellular distribution of alveolar
      surfactant, extracted through bronchoalveolar lavage of anesthetized cats and
      rabbits. This was correlated to several morphometric and ventilatory variables of
      these animals. 2. Lung weight was significantly larger in the cat while
      respiratory frequency and minute ventilation were significantly larger in the
      rabbit. No significant differences were observed in tidal volume, total lung
      capacity, P(a)O2, P(a)CO2 and pH(a). 3. While both species had similar protein
      contents in the bronchoalveolar lavage, rabbits had larger phospholipid contents,
      mostly distributed in the lighter, more active subfractions. 4. With regard to
      the estimated values obtained from allometric equations derived for mammals, the
      rabbit presented a lung weight of nearly one-third of the estimated one, an
      exceedingly larger minute ventilation (by nearly 60%) and a respiratory frequency
      twice the calculated one. 5. We suggest that the different distribution of
      alveolar surfactant in these species may be explained by disparities in their
      ventilatory demands, the rabbit having a higher respiratory frequency and a
      larger minute ventilation, performed by a mass of lung tissue lower than that
      corresponding to its body mass.

PMID- 1355033
TI  - Age-related changes in GSH content of eyes in mice--a comparison of senescence
      accelerated mouse (SAM) and C57BL/J mice.
AB  - 1. Age-related changes in glutathione (GSH) content of eye lenses were
      investigated in senescence-accelerated mouse (SAM) and C57BL/J mice. 2. The
      decrease of GSH content with aging is markedly observed in SAM strains. 3. The
      oxidized glutathione (GSSG) content of eyes increased significantly with aging in
      SAM. 4. Ophthalmic changes, including cataract, increased with age in SAM alone.
      5. The decrease of GSH content and the increase of GSH oxidation may be involved
      in the pathogenesis of cataract in SAM.

PMID- 1355035
TI  - Blood parameters in draught oxen during work: relationship to physical fitness.
AB  - 1. Four Zebu and four Simmental oxen were submitted to moderate and exhaustive
      work. Venous blood samples were taken before, immediately after and 30 min after
      work and assayed for several blood parameters. 2. Draught work led to a decrease
      in carbon dioxide (pvCO2) and increases in pH, oxygen (pvO2), triglycerides, free
      fatty acids (FFA) and lactate. 3. Zebu oxen had higher pvCO2 and FFA and lower
      pH, pvO2 and lactate in response to exercise. 4. Ratios of individual draught
      power output and values of pvO2 and lactate after work enable the identification
      of fit and/or weak individuals.

PMID- 1355034
TI  - Adrenergic receptor-mediated increase of intracellular Ca2+ concentration in
      isolated bovine corneal epithelial cells.
AB  - 1. We determined if Ca2+ is a second messenger for adrenergic receptor-effector
      coupling in bovine corneal epithelial cells. 2. Methoxamine (10(-5) M)
      selectively increased intracellular Ca2+ concentration (Cai) by 65%. This
      increase was only partially suppressed through the removal of extracellular Ca2+
      or pretreatment with 10(-6) M verapamil. 3. The beta-adrenergic-mediated
      increases in Cai were entirely dependent on extracellular Ca2+. These increases
      were directly elicited through stimulation of adenylate cyclase because 10(-6) M
      isoproterenol and the active analogues of forskolin (10(-5) M) all elevated Cai.
      4. Therefore, increases in Cai serve a second messenger function for alpha-1 and
      beta-adrenergic receptor-effector coupling.

PMID- 1355036
TI  - Hematological and plasma chemical characteristics in beech marten (Martes foina).
AB  - 1. The normal values of hematological and clinical-chemical variables in plasma
      of 21 males and 27 females of beech marten (Martes foina) have been illustrated
      and compared to corresponding normal values in mink (Mustela vison) and ferret
      (Mustela putorius). 2. The number of erythrocytes, the hematocrit value, and the
      hemoglobin concentration were higher in male than in female beech marten. 3.
      Divergences according to age in the investigated variables have been found. 4.
      The erythrocytes in beech marten are clearly smaller in size and volume and have
      a lower mean corpuscular hemoglobin than the erythrocytes in mink and ferret.

PMID- 1355037
TI  - Serum-cell interactions in transmission of sarcoma in the soft shell clam, Mya
      arenaria L.
AB  - 1. Serum proteins from sarcomatous soft shell clams, Mya arenaria L., enhanced
      transmission of sarcoma. 2. Sarcoma cells were isolated and administered to the
      recipients at the same cell density in different sarcoma-protein-free diluents:
      seawater, serum from normal clams, heat-treated sarcoma serum or protease
      digested sarcoma serum. 3. Transmission in these groups was significantly slower
      than in the group where cells were administered in intact sarcoma serum,
      demonstrating that the tumor promoting factors in the serum were heat-sensitive
      proteins. 4. Normal hemocytes administered in sarcoma serum caused mortality but
      not sarcoma transmission, suggesting the presence of cytotoxic factors in sarcoma
      serum.

PMID- 1355038
TI  - Autonomic basis for hypoxia-induced hyperglycaemia in toads (Bufo paracnemis).
AB  - 1. Toads were exposed to steady hypoxic conditions (inspired PO2 = 40 mmHg) for
      60 min. 2. Within the exposure time, glucose concentrations rose from about 30
      mg% to a steady level of 45 mg%. The development of hyperglycaemia reached a
      stable level within 40 min. 3. This effect was eliminated by treatment with
      either propranolol or atropine, suggesting combined cholinergic and adrenergic
      activation.

PMID- 1355039
TI  - Urate excretion by the cat kidney.
AB  - 1. The renal handling of urate by the cat kidney was investigated during
      continuous infusion of urate. 2. Fractional urate excretion (FE(UA)) in cats was
      0.57 +/- 0.04, indicating net reabsorption of urate. In contrast, FE(UA) in
      rabbits was 1.76 +/- 0.08, reflecting net secretion of urate. 3. Fractional PAH
      excretion (FE(PAH)) was 3.94 +/- 0.26 in cats and 4.12 +/- 0.76 in rabbits,
      showing net secretion in both species. 4. FE(UA) in cats was dependent on urine
      flow, but was independent of plasma urate concentration. 5. The urate excretion
      in cats was enhanced by probenecid, but was insensitive to PAH and PZA. 6. The
      PAH excretion in cats was reduced by probenecid, but was unaltered by urate and
      PZA. 7. These results indicate that urate is handled in the cat kidney by a
      unique transport system which is distinct from that for organic anions.

PMID- 1355040
TI  - Is sodium necessary for stimulus-secretion coupling in toad (Caudiverbera
      caudiverbera) adrenal chromaffin cells?
AB  - 1. Chromaffin cells of the toad were used to investigate the effects of total
      replacement of extracellular Na+ by monovalent cations or sucrose on secretion of
      catecholamine (CA). 2. K+, Rb+ or Cs+ in place of Na+ produced an immediate
      secretory response, which are dependent on extracellular Ca2+ and it was blocked
      by Co2+. Li+ or choline+ did not affect basal secretion. 3. Isosmotic replacement
      of Na+ by sucrose caused CA secretion even in the absence of external Ca2+ or in
      the presence of Ca-channel blockers. 4. Tetraethylammonium decreased the extent
      of CA release produced by either K+ or Rb+. 5. The secretagogue effect of Na+/K+,
      Na+/Rb+ or Na+/Cs+ replacement could be explained by a depolarization of the cell
      membrane, which ultimately will cause Ca2+ influx through voltage-dependent Ca
      channels. However, the present results indicate that Na+ may be sufficient but
      not necessary for CA secretion.

PMID- 1355041
TI  - Thermoregulation and evaporative cooling in the cicada Okanagodes gracilis
      (Homoptera: Cicadidae).
AB  - 1. Okanagodes gracilis uses a combination of physiological and behavioral
      mechanisms to regulate body temperature (Tb) to a prescribed range. 2. High
      thermal tolerances (48.6 degrees C Tb) and evaporative cooling permit the species
      to remain active during the hottest parts of the day. 3. The regression of Tb on
      ambient temperature (Ta) (Y = 0.142X + 34.63) intersects the isothermal line at
      40.4 degrees C, below the shade-seeking value of 41.2 degrees C. 4. In the
      laboratory, weight (water) loss is faster at higher (46 degrees C) than at lower
      (43 degrees C) temperatures; the cicadas were able to survive mass losses of 25%
      in the laboratory. 5. Pores in the dorsal thorax and abdomen are the probable
      sites of water loss. 6. O. gracilis is the first cicada reported that is able to
      continue activity while simultaneously feeding and evaporatively cooling. 7.
      Behavioral mechanisms of thermoregulation and the possible thermoregulatory value
      of the species' coloration are discussed.

PMID- 1355044
TI  - Abstracts of papers presented at the Tianjin International Symposium on LHRH
      Analogues. Tianjin, China, September 24-26, 1991.

PMID- 1355043
TI  - L-tryptophan alleviates fatty liver and modifies hepatic microsomal mixed
      function oxidase in laying hens.
AB  - 1. Three experiments were conducted to study the effect of dietary L-tryptophan
      supplementation (250-1000 ppm) on lipid accumulation, an occurrence of
      hemorrhages and microsomal mixed function oxidase in the liver of laying hens. 2.
      Dietary L-tryptophan supplementation resulted in significant decreases in hepatic
      lipids, in particular triglyceride, and occurrence of hemorrhage in laying hens.
      3. Hepatic lipid accumulation by estrogen injection in starved-refed growing
      chicks decreased as dietary tryptophan content increased. 4. Supplementation of L
      tryptophan at 1000 mg/kg diet enhanced alanine aminotransferase activity in the
      hepatic tissue and at 500 mg/kg diet, increased cytochrome b5, a component of the
      mixed function oxidase, in the hepatic microsomes. 5. These results demonstrate
      that L-tryptophan alleviates fatty liver in laying hens and modifies microsomal
      mixed function oxidase in the liver.

PMID- 1355042
TI  - Digestive enzyme levels and histopathology of pancreas disease in farmed Atlantic
      salmon (Salmo salar).
AB  - 1. The pancreatic digestive enzyme activities of trypsin and chymotrypsin were
      assessed in vitro and were found to correlate well with the histological changes
      characteristic of pancreas disease (PD) in farmed Atlantic salmon (Salmo salar).
      2. Pancreatic enzyme activity was assessed in vivo using the chymotrypsin
      specific substrate N-benzoyl-L-tyrosyl-p-aminobenzoic acid. In all cases,
      significantly less p-aminobenzoic acid was excreted by fish later found to be
      suffering from PD. 3. It is concluded that the in vitro digestive enzyme assay
      was effective in diagnosing PD with the in vivo method, indicating further
      promise for assessing exocrine pancreatic function.

PMID- 1355045
TI  - Pleiotropic, multidrug-resistant phenotype and P-glycoprotein: a review.
AB  - This article is a brief review of recent knowledge about the pleiotropic
      resistant phenotype--multidrug-resistant (MDR) phenotype--which is responsible
      for cross-resistance in cancer chemotherapy. Thus it is possible to explain
      chemoresistance to vinca alkaloids, podophyllotoxins and anthracyclines. The MDR
      phenotype is associated with reduced intracellular drug accumulation by drug
      efflux, utilizing transmembrane P-glycoprotein (Gp170). The overexpression of
      Gp170 in normal and cancer tissues and the genetics are reported.

PMID- 1355046
TI  - 7-substituted pterins in humans with suspected pterin-4a-carbinolamine
      dehydratase deficiency. Mechanism of formation via non-enzymatic transformation
      from 6-substituted pterins.
AB  - A recently described new form of hyperphenylalaninemia is characterized by the
      excretion of 7-substituted isomers of biopterin and neopterin and 7-oxo-biopterin
      in the urine of patients. It has been shown that the 7-substituted isomers of
      biopterin and neopterin derive from L-tetrahydrobiopterin and D
      tetrahydroneopterin and are formed during hydroxylation of phenylalanine to
      tyrosine with rat liver dehydratase-free phenylalanine hydroxylase. We have now
      obtained identical results using human phenylalanine hydroxylase. The identity of
      the pterin formed in vitro and derived from L-tetrahydrobiopterin as 7-(1',2'
      dihydroxypropyl)pterin was proven by gas-chromatography mass spectrometry.
      Tetrahydroneopterin and 6-hydroxymethyltetrahydropterin also are converted to
      their corresponding 7-substituted isomers and serve as cofactors in the
      phenylalanine hydroxylase reaction. Dihydroneopterin is converted by
      dihydrofolate reductase to the tetrahydro form which is biologically active as a
      cofactor for the aromatic amino acid monooxygenases. The 6-substituted pterin to
      7-substituted pterin conversion occurs in the absence of pterin-4a-carbinolamine
      dehydratase and is shown to be a nonenzymatic process. 7-Tetrahydrobiopterin is
      both a substrate (cofactor) and a competitive inhibitor with 6
      tetrahydrobiopterin (Ki approximately 8 microM) in the phenylalanine hydroxylase
      reaction. For the first time, the formation of 7-substituted pterins from their 6
      substituted isomers has been demonstrated with tyrosine hydroxylase, another
      important mammalian enzyme which functions in the hydroxylation of phenylalanine
      and tyrosine.

PMID- 1355047
TI  - Purification of the main somatostatin-degrading proteases from rat and pig
      brains, their action on other neuropeptides, and their identification as
      endopeptidases 24.15 and 24.16.
AB  - The main somatostatin-degrading proteases were purified from rat and pig brain
      homogenates and characterized as thiol- and metal-dependent endoproteases. Two
      types of proteases with apparent native and subunit molecular masses of 70 kDa
      and 68 kDa could be differentiated in both species. Beside somatostatin, both
      hydrolyzed several other neuropeptides with chain lengths between 8 and 30 amino
      acid residues. Cleavage sites were generally similar or identical, but some clear
      exceptions were observed for enzymes from both species which could be used to
      differentiate between the two proteases. The 68-kDa protease cleaved somatostatin
      at three bonds (Asn5-Phe6, Phe6-Phe7 and Thr10-Phe11) and neurotensin only at the
      Arg8-Arg9 bond, whereas the 70-kDa protease digested somatostatin at only two
      bonds (Phe6-Phe7 and Thr10-Phe11) and neurotensin as well as acetylneurotensin-(8
      13) additionally (pig protease) or almost exclusively (rat protease) at the Pro10
      Tyr11 bond. Relative rates for the digestions of various peptides were, however,
      more dependent on the species than on the type of protease. Cleavage sites for
      angiotensin II, bradykinin, dynorphin, gonadoliberin and substance P were, apart
      from different rates, identical for both proteases. In both species the 68-kDa
      protease was found to be mainly, but not exclusively, soluble and not membrane
      associated, whereas the inverse was detected for the 70-kDa protease. Based on
      distinct molecular and catalytic properties, the 68-kDa protease is supposed to
      be congruent with the endopeptidase 24.15 (EC 3.4.24.15), the 70-kDa protease
      with endopeptidase 24.16 (EC 3.4.24.16, neurotensin-degrading endopeptidase).
      This investigation demonstrates that both proteases hydrolyze various
      neuropeptides with similar cleavage sites, but with species-dependent activity.
      Species-independent distinctions are the exclusive action of endopeptidase 24.16
      on acetylneurotensin-(8-13) and liberation of free Phe from somatostatin only by
      endopeptidase 24.15.

PMID- 1355048
TI  - Maturation of Xenopus laevis oocyte by progesterone requires poly(A) tail
      elongation of mRNA.
AB  - Meiotic maturation of Xenopus laevis oocytes by progesterone requires translation
      of stored maternal mRNAs. We investigated the role of poly(A) tail elongation of
      mRNAs during this process using cordycepin, which inhibits poly(A) tail
      elongation of mRNAs. When oocytes were treated with the buffer containing 10 mM
      cordycepin for 12 h, concentration of 3'-dATP in cytosol of oocytes increased to
      0.7 mM, while that of ATP remained constant at around 1.2 mM. Incorporation of
      [32P]AMP into poly(A) mRNA was inhibited almost completely by this treatment.
      Progesterone-induced germinal vesicle breakdown (GVBD) was also abolished. Dose
      dependence of inhibition of progesterone-induced GVBD on cordycepin was similar
      to that of [32P]AMP incorporation into poly(A) mRNA. However, maturation
      promoting factor-induced GVBD was unaffected by treatment of oocytes with
      cordycepin. Furthermore, the inhibition of GVBD by cordycepin was rescued by
      removal of cordycepin even in the presence of actinomycin D. Therefore, we
      concluded that poly(A) tail elongation of mRNA is required for induction of
      meiotic maturation of X. laevis oocytes. In addition, progesterone induced a 2.7
      fold activation of [32P]AMP incorporation into the poly(A) tail of mRNA after a
      lag period of 3 h whereas GVBD was induced after 6-8 h from the progesterone
      treatment. Syntheses of most of the proteins were unaffected by treatment of
      oocytes with progesterone or cordycepin. However, syntheses of several proteins
      were increased or decreased by progesterone and cordycepin treatment.

PMID- 1355049
TI  - Microvillar enzyme activity in amniotic fluid, extraembryonic coelomic fluid and
      maternal serum in the first trimester of pregnancy.
AB  - The activities of two microvillar enzymes, gamma-glutamyl transpeptidase and
      total alkaline phosphatase, have been measured in samples of amniotic fluid and
      extraembryonic coelomic fluid obtained by high-resolution transvaginal ultrasound
      guided amniocentesis from 40 women between 7 and 12 weeks of gestation. There was
      a highly significant difference between gamma-glutamyl transpeptidase activity in
      amniotic fluid (median level 31 U/l; range 2-409 U/l) and extraembryonic coelomic
      fluid (median level 2 U/l; range less than 2-16 U/l) (P less than 0.001; Mann
      Whitney U-test). Alkaline phosphatase activity was not detected in 84% of
      amniotic fluid samples and 97% of extraembryonic coelomic fluid samples. No
      difference was found between total alkaline phosphatase activity in these fluids
      (P = 0.14; Mann-Whitney U-test). Enzyme activities in amniotic fluid increased
      with gestational age. A significant linear correlation was found between amniotic
      fluid gamma-glutamyl transpeptidase activity and stage of gestation (r = 0.86; P
      less than 0.001) and total alkaline phosphatase activity in amniotic fluid and
      stage of gestation (r = 0.66; P less than 0.001).

PMID- 1355050
TI  - Regulated expression of vasopressin gene by cAMP and phorbol ester in primary rat
      fetal hypothalamic cultures.
AB  - Using dispersed cultures of fetal rat hypothalami, we studied the effects of
      forskolin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA),
      activators of protein kinase A and C, respectively, upon vasopressin (VP)
      secretion, VP mRNA expression and VP mRNA poly(A) tail length. Forskolin
      stimulated the VP mRNA content and peptide secretion 2.6-fold and induced an
      increase in the poly(A) tail length of approximately 90 nucleotides. TPA induced
      an increase in VP mRNA size and stimulated 1.9-fold the secretion of VP without
      an increase in VP mRNA content. Depolarization with potassium induced an increase
      in the VP peptide secreted of 2.2-fold, with no effect on the VP mRNA content or
      size. Increased osmolality had no effect on either VP peptide or VP mRNA. We
      conclude that VP expression in cultured fetal rat hypothalamic cells is regulated
      via both protein kinase A and protein kinase C pathways.

PMID- 1355051
TI  - Regulation of UCP gene expression in brown adipocytes differentiated in primary
      culture. Effects of a new beta-adrenoceptor agonist.
AB  - Primary cultures of precursor cells from mouse and rat brown adipose tissue (BAT)
      were used to study the effect of a new beta-agonist (ICI D7114) on the uncoupling
      protein (UCP) gene expression. ICI 215001 (the active metabolite of D7114)
      increased the expression of UCP and its mRNA in brown adipocytes differentiating
      in vitro in a dose-dependent manner. This stimulating effect was not inhibited by
      propranolol, a non-specific beta-antagonist, but was partially reduced by
      bupranolol, a beta 3-antagonist. No expression of UCP mRNA was ever induced by
      ICI 215001 in white adipocytes differentiated in vitro. It was concluded that the
      drug could affect the brown adipose cells through a beta 3-pathway. It could
      clearly modulate the expression of UCP in brown adipocytes differentiated in
      vitro, but was not able by itself to turn on the gene.

PMID- 1355052
TI  - Inhibitory effect of somatostatin on cAMP accumulation and calcitonin secretion
      in C-cells: involvement of pertussis toxin-sensitive G-proteins.
AB  - The effect of somatostatin on cAMP accumulation and calcitonin secretion in C
      cells of the rat medullary thyroid carcinoma cell line rMTC 6-23 was
      investigated. Intracellular cAMP accumulation as well as calcitonin secretion
      could be dose-dependently stimulated by rat growth hormone releasing factor
      (rGRF). The long-acting somatostatin analogue octreotide inhibited rGRF
      stimulated cAMP accumulation and calcitonin secretion dose dependently but failed
      to block 8-bromo-cAMP-stimulated calcitonin secretion. The inhibitory effect of
      octreotide on rGRF-induced calcitonin secretion was partially abolished by
      pretreating the cells with pertussis toxin. The octreotide effect was not due to
      changes in the degradation of cAMP, as it was similarly seen in the presence of
      isobutylmethylxanthine. Thus we conclude that pertussis toxin-sensitive G
      proteins are involved in the cAMP-mediated regulation of calcitonin secretion in
      C-cells.

PMID- 1355053
TI  - Hemorrhagic gastropathy in epidemic nephropathy.
AB  - A patient with epidemic nephropathy (NE) and with gastrointestinal symptoms and
      hemorrhagic gastropathy prompted us to study further 10 consecutive patients with
      NE. Gastroscopy was carried out within 1 to 4 weeks after the beginning of the
      symptoms, and in every case a hemorrhagic gastropathy was observed. Hemorrhagic
      lesions were more marked, the shorter the elapsed time interval from the
      beginning of symptoms. Hemorrhagic changes were always more prominent in the
      proximal than in the distal part of the stomach. In 7 of 10 patients lesions were
      also observed in the duodenum. Colonoscopy was done in one patient and it showed
      similar spotty hemorrhages, suggesting that hemorrhagic lesions were not limited
      to the gastroduodenal mucosa only. Histological studies disclosed that the
      hemorrhagic lesions were associated with edema in the lamina propria, but without
      inflammatory changes. Follow-up gastroscopy in three patients 3 to 8 weeks later
      showed disappearance of hemorrhagic lesions in every patient. Thus, these results
      show for the first time that hemorrhagic gastropathy is a common finding in NE,
      and it may explain the abdominal symptoms and gastrointestinal bleeding in some
      of these patients. However, the mechanism of the hemorrhagic lesions needs
      further exploration.

PMID- 1355054
TI  - Percutaneous endoscopic biliary stent placement after Whipple resection.

PMID- 1355055
TI  - Polyarteritis nodosa of the gastrointestinal tract with endoscopically documented
      duodenal and jejunal ulceration.

PMID- 1355056
TI  - Effects of LP-805, a new vasodilating agent, on rat thoracic aorta.
AB  - 1. In canine coronary arteries, the contraction induced by prostaglandin F2 alpha
      (PGF2 alpha), but not by 65.9 mM K+, were relaxed by LP-805 (0.01-10 microM) in a
      concentration-dependent manner. 2. In rat thoracic aorta, LP-805 (0.1-10 microM)
      also relaxed the preparations contracted with norepinephrine (NE) and PGF2 alpha,
      but did not relax the contraction produced by 65.9 mM K+. 3. LP-805 (3-10 microM)
      inhibited the increase in cytosolic Ca2+ levels and contractions evoked by NE (1
      microM) in the absence or presence of external Ca2+ in rat thoracic aorta. 4. LP
      805 (0.1-10 microM) inhibited synthesis of IP3 induced by NE (0.3 microM) and
      cyclic AMP phosphodiesterase activity, and increased intracellular cyclic AMP
      levels in rat thoracic aorta. 5. These results suggest that a vasodilatory effect
      of LP-805 is due to inhibiting the increase in cytosolic Ca2+ levels via
      stimulation of various receptors, modulating second messenger synthesis.

PMID- 1355057
TI  - Mode of relaxing action of FK336, a new antianginal agent, in rabbit aorta.
AB  - 1. FK336 (10(-6)-10(-4) M) inhibited contractile responses to norepinephrine
      (NE), KCl and Ca2+ in isolated rabbit aortas. 2. Relaxing effect of FK336 on KCl
      response was inhibited by nitroglycerin (NG), but not by nifedipine or verapamil.
      3. FK336 inhibited residual NE response and a subsequent Ca2+ response in Ca(2+)
      free medium. FK336 did not affect the inositol monophosphate level. 4. Relaxing
      effect of FK336 on NE response was inhibited by methylene blue, NG, K(+)-channel
      inhibitors and acetylcholine (ACh), and potentiated by M&B 22,948 and
      theophylline. 8-Br cGMP and dibutyl cAMP had no effect. 5. FK336 increased cGMP
      level in rat aorta. 6. Potentiation of isoproterenol-relaxation by FK336 was
      inhibited by methylene blue. 7. The inhibitory effect of ACh on FK336-relaxation
      was eliminated by endothelium removal, nordihydroquaiaretic acid and guinacrine,
      but not by indomethacin. These treatments themselves did not affect FK336
      relaxation. 8. The mode of vasorelaxing action of FK336 is discussed.

PMID- 1355058
TI  - Control of gastric mucus phospholipid content and composition by cholinergic and
      adrenergic mediators.
AB  - 1. The secretion of choline-containing phospholipids by gastric mucosal cells in
      response to neural mediators was investigated using beta-adrenergic and
      cholinergic agents. 2. A 2.7-fold increase in phospholipid secretion occurred
      with isoproterenol, while pilocarpine evoked 1.4-fold increase and the effects
      were inhibited by the respective antagonists. 3. The phospholipid secretory
      responses were stimulated by dibutyryl-cAMP and phorbol myristate acetate (PMA),
      but not by 4 alpha-phorbol-12,13-didecanoate which does not activate protein
      kinase C. The effects of dibutyryl-cAMP and PMA were additive, the the PMA
      induced phospholipid secretion was inhibited by a protein kinase C inhibitor,
      tetracaine. 4. The phospholipids secreted in response to isoproterenol showed a
      2.1-fold decrease in lysophosphatidylcholine, while those secreted in response to
      pilocarpine were enriched 2.3-fold in lysophosphatidylcholine, and 1.5-fold in
      sphingomyelin, and showed 23% lower content of phosphatidylcholine. 5. The
      results suggest that cholinergic and beta-adrenergic mediators participate in
      defining the gastric mucus phospholipid content and composition, and hence
      influence the mucosal protective capability.

PMID- 1355059
TI  - Absence of denervation supersensitivity to neurokinin A in the rat vas deferens.
AB  - 1. Unilateral denervation of the rat vas deferens (RVD) was performed under
      anesthesia. The animals were allowed to recover 4 or 10 days and then
      concentration-effect (C-E) curves to noradrenaline (NA) and neurokinin A (NKA)
      were constructed in denervated and control RVD. 2. Tissues denervated 4 or 10
      days produced NA responses shifted 20-fold to the left with maxima 130% of
      control. 3. NKA C-E curves in denervated RVD were not significantly different
      from control. 4. Phenylephrine exhibited a 6-fold increase in tissue sensitivity
      after denervation. 5. Chronic denervation of the vas deferens resulted in
      significant postsynaptic supersensitivity to alpha 1-adrenoceptor agonists but
      not to NKA.

PMID- 1355060
TI  - Location, characterization and expression of lytic enzyme-encoding gene, lytA, of
      Lactococcus lactis bacteriophage phi US3.
AB  - Gene lytA, which encodes lytic enzyme (LytA), of the isometric Lactococcus lactis
      bacteriophage phi US3, was cloned and expressed in Escherichia coli. The lytA
      gene was located on the physical map of the phi US3 32-kb DNA that contains
      cohesive ends. Initial expression of lytA was detected by lysis of an overlay of
      cells of the phage-sensitive strain, L. lactis SK112. However, LytA appeared to
      have a broad spectrum and induced lysis in more than 30 different lactococcal
      strains. The nucleotide sequence of lytA showed a single open reading frame (ORF)
      of 774 bp encoding a protein of 258 amino acids (aa) with a calculated M(r) of
      28,977. This is in agreement with the size of 29 kDa as determined for LytA
      produced in E. coli using a T7 expression system. The lytA gene is preceded by an
      ORF that may code for a hydrophobic peptide of 66 aa containing a putative
      secretion signal, and two putative transmembrane helices. The deduced aa sequence
      of the phage phi US3 LytA shows similarities to that of the autolysin of
      Streptococcus pneumoniae which is known to be an amidase.

PMID- 1355061
TI  - Mini- and micro-satellites in the genome of rodent malaria parasites.
AB  - Higher eukaryotes contain within their DNA numerous arrays of repetitive DNA,
      many of which are known as satellite DNAs and display extensive variability. The
      presence of these repeats has been demonstrated for various species and they have
      been used for genetic identification and classification. Here, it is demonstrated
      that Southern hybridisation of DNA from rodent malaria parasites allows detection
      of micro- and minisatellite sequences in the genome of Plasmodium species.
      Closely related lines of malaria parasites exhibit a monomorphic hybridisation
      pattern, which is in contrast to the allelic variation observed in higher
      eukaryotes. Among different species, however, restriction-fragment length
      polymorphism was observed. Pulsed-field gel electrophoretic chromosome separation
      showed that the probes used in this study [33.15, 33.6, (CAC)n and (GT)n] detect
      several loci spread over different chromosomes.

PMID- 1355062
TI  - Structure and chromosomal localization of the gene encoding barley seed
      peroxidase BP 2A.
AB  - A clone, lambda Prx6.1, coding for a barley seed peroxidase (BP; EC 1.11.1.7),
      was isolated from a genomic library using a cDNA coding for the barley seed
      peroxidase, BP 1, as a probe. The nucleotide sequence coded for a BP showing 73%
      amino acid (aa) sequence identity with BP 1 and less than 50% similarity with
      other sequenced plant peroxidases. The aa composition is 92% identical to that
      determined for BP 2 purified from mature barley grains, and therefore the gene
      product is named BP 2A. The alignment suggests that the coding region is
      interrupted by a 76-bp intron having the consensuses GT and AG, at the 5' and 3'
      ends, respectively. Alignment with BP 1 suggests that BP 2A has a leader peptide
      of 36 aa and the mature protein is 319 aa. Alanine and leucine account for 50% of
      the residues of the leader peptide. Of the codons used 90% have a C or G in the
      third position. The promoter shows a putative abscisic acid-response element, 5'
      GTACGTGTC, 115 bp upstream from the start codon. The BP 2A-encoding gene was RFLP
      mapped on barley chromosome 3, and we suggest for this peroxidase locus the name
      Prx6.

PMID- 1355064
TI  - Radiotherapy/chemotherapy interactions in cancer therapy: potential benefits and
      hazards in the clinic. 26th annual San Francisco Cancer Symposium. San Francisco,
      February 16-17, 1991.

PMID- 1355063
TI  - Sleep disorders with aging: evaluation and treatment.
AB  - Sleep disorders are especially common among elderly patients and may be the
      result of psychiatric illness, a medical problem, poor sleep habits, or a primary
      sleep disorder. Because a sleep complaint (especially insomnia) is only a
      symptom, the physician must undertake a careful evaluation in an attempt to
      identify a specific treatable cause. Although some patients may require referral
      to a psychiatrist or sleep disorders clinic, many patients may benefit from
      behavioral strategies, such as improved sleep hygiene. In general, hypnotics
      should be prescribed for only a limited period of time and should be combined
      with other therapeutic approaches in patients with chronic insomnia.

PMID- 1355065
TI  - [Tumor necrosis factor alpha in systemic lupus erythematosus: evaluation by
      restriction fragment length polymorphism and production by peripheral blood
      mononuclear cells].
AB  - Human TNF alpha locus locates between HLA-B and DR region on the short arm of
      chromosome 6. The 5.5 kb and 10.5 kb of TNF alpha restriction fragment length
      polymorphic (RFLP) bands were identified by Southern hybridization using a
      restriction enzyme, NcoI. The frequencies of those bands were not different among
      patients with systemic lupus erythematosus (SLE), those with rheumatoid arthritis
      and normal controls. In the lupus patients, proteinuria was more frequent in the
      patients with the 5.5 kb RFLP band (19/39: 48.7%) than those without 5.5 kb band
      (7/35: 20%) (p less than 0.05). Furthermore, this band was strongly associated
      with the haplotype HLA B44-DRw13-DQw1. In order to investigate the association
      between this gene polymorphism and the production of TNF alpha, peripheral blood
      mononuclear cells from patients with SLE and normal controls were cultured for 24
      hours with lipopolysaccharide and concanavalin A and the amount of TNF alpha in
      the supernatant was measured by enzyme linked immunosorbent assay. The TNF alpha
      production of lupus patients was not statistically different from that of normal
      controls. The production of TNF alpha was not related to 5.5 kb RFLP band, but in
      the patients with SLE, the mean value of TNF alpha in patients with the 5.5 kb
      RFLP band tended to be higher than those without the band. Lupus patients were
      divided into two groups by the production of TNF alpha i.e. low TNF alpha
      inducibility group and high TNF alpha inducibility group. Patients with
      proteinuria were more frequent in patients of the high TNF alpha inducibility
      group than those of low TNF alpha inducibility group (p less than 0.05). There
      were four patients with HLA B44-DRw13-DQw1 who had the 5.5 kb RFLP band and three
      of them belonged to the high TNF alpha inducibility group with nephrosis. These
      data suggest that TNF alpha and HLA are possibly associated with the severity of
      lupus nephritis.

PMID- 1355066
TI  - Identification of a missense phenylketonuria mutation at codon 408 in Chinese.
AB  - A single base transition of G to A at codon 408 of the phenylalanine hydroxylase
      gene is identified. This missense mutation results in the substitution of Arg408
      for Gln408 (R408Q) and accounts for about 5% of phenylketonuria (PKU) chromosomes
      among Chinese. This mutation is in linkage disequilibrium with restriction
      fragment length polymorphism haplotype 4. In addition, another mutation (R408W),
      at the same codon and prevalent on haplotype 2 PKU chromosomes in Caucasians, is
      identified in a PKU allele of haplotype 41. Previously, this mutation has been
      observed on a haplotype 44 background in Chinese PKU patients.

PMID- 1355067
TI  - A haplotype-linked four base pair deletion upstream of the A gamma globin gene
      coincides with decreased gene expression.
AB  - During normal human development, a switch is classically observed in the relative
      expression of the two gamma globin genes, the G gamma/A gamma ratio varying from
      70/30 at birth to 40/60 by the end of the first year. An exception to this
      developmental pattern is linked to the presence of an XmnI restriction site at a
      position -158 to the Cap site of the G gamma gene. Another exception is observed
      in individuals homozygous for two easily detectable variations of the A gamma
      gene: the presence of a threonine residue at codon 75 and a HindIII site within
      the second intron. A 4-bp deletion has been described around position -225 in
      some thalassemic patients presenting with these variations. In this study, we
      find this deletion to be haplotype-linked in a series of 156 individuals of
      various ethnic origins and presenting with various normal and pathological
      phenotypes. In sickle cell patients heterozygous for this 4-bp deletion, the
      relative expression of the A gamma genes on the two chromosomes can be measured
      by estimating the A gamma T and A gamma I chains, the former always being
      synthesized at a lower rate. These results suggest a functional role for the
      deleted sequence.

PMID- 1355068
TI  - DNA analysis in Turkish Duchenne/Becker muscular dystrophy families.
AB  - The molecular genetics of Duchenne/Becker muscular dystrophy was investigated in
      81 affected Turkish families. Deletions were detected by multiplex polymerase
      chain reaction assays and cDNA Southern analyses. The distribution of the
      deletions along the gene and their correlation to clinical phenotype were
      different from the studies reported on other populations. Moreover, DNA
      polymorphisms in mothers were determined using 8 DNA probes and three CA repeat
      sequences, and a high degree of informativeness was observed.

PMID- 1355069
TI  - Exclusion mapping of the X-linked dominant chondrodysplasia
      punctata/ichthyosis/cataract/short stature (Happle) syndrome: possible
      involvement of an unstable pre-mutation.
AB  - Homology with the mouse bare patches mutant suggests that the gene for the X
      linked dominant chondrodysplasia punctata/ichthyosis/cataract/short stature
      syndrome (Happle syndrome) is located in the human Xq28 region. To test this
      hypothesis, we performed a linkage study in three families comprising a total of
      12 informative meioses. Multiple recombinations appear to exclude the Xq28 region
      as the site of the gene. Surprisingly, multiple crossovers were also found with
      26 other markers spread along the rest of the X chromosome. Two-point linkage
      analysis and analysis of recombination chromosomes seem to exclude the gene from
      the entire X chromosome. Three different mechanisms are discussed that could
      explain the apparent exclusion of an X-linked gene from the X chromosome by
      linkage analysis: (a) different mutations on the X chromosome disturbing X
      inactivation, (b) metabolic interference, i.e. allele incompatibility of an X
      linked gene, and (c) an unstable pre-mutation that can become silent in males. We
      favour the last explanation, as it would account for the unexpected sex ratio
      (M:F) of 1.2:1 among surviving siblings, and for the striking clinical
      variability of the phenotype, including stepwise increases in disease expression
      in successive generations.

PMID- 1355070
TI  - A HindIII/BglII dystrophin gene polymorphism in the African-American population.
AB  - We describe a common dystrophin gene polymorphism in the black population that
      alters both HindIII and BglII restriction sites.

PMID- 1355071
TI  - A novel NcoI polymorphism creates a fifth haplotype in the 3' untranslated region
      of CKM.
AB  - A novel NcoI polymorphism has been detected in the 3' untranslated region of the
      creatinine kinase (CKM) gene. The addition NcoI restriction site creates a fifth
      haplotype for the NcoI and TaqI restriction fragments length polymorphisms at
      this locus, and segregates with the myotonic dystrophy gene in 3 generations of
      an affected family.

PMID- 1355072
TI  - Comparison of restriction fragment length polymorphisms of proto-oncogenes in
      native Hawaiians and other ethnic groups in Hawaii.
AB  - The relative genetic diversity of selected proto-oncogenes in the native Hawaiian
      gene pool was examined by comparing the restriction fragment length polymorphisms
      of these genes in a group of 23 individuals with at least part Hawaiian ancestry,
      and in 20 individuals from other ethnic groups. Twenty-one combinations of the
      proto-oncogenes, c-fms, c-myc, L-myc, c-Ha-ras, and c-Ki-ras, tested with 1 or
      more of the restriction enzymes Bam HI, Eco RI, Hind III, Pst I, Pvu I and Kpn I
      were examined. Sixteen of these did not exhibit RFLPs in Hawaiians or in other
      ethnic groups. Four of the combinations exhibiting RFLPs in native Hawaiians
      exhibited similar-sized restriction fragments in the other ethnic groups. Only in
      the case of c-myc digested with Pst I were 5 individuals of Hawaiian ancestry
      found to have an RFLP which has not been detected in other ethnic groups. These 5
      cases exhibited a 13-kb c-myc fragment in addition to the 5.5-kb fragment found
      in most Hawaiians and always present in other ethnic groups. The presence in
      Hawaiians of most RFLPs found in other ethnic groups indicates that the genetic
      diversity of proto-oncogenes in the gene pool of native Hawaiians is not
      substantially less than that of other ethnic groups.

PMID- 1355073
TI  - Tyrosine hydroxylase gene not linked to manic-depression in seven of eight
      pedigrees.
AB  - We ascertained 8 multigenerational pedigrees afflicted with multiple cases of
      bipolar and recurrent major depressive disorder. Alterations in dopaminergic and
      noradrenergic neurotransmission have been implicated in the pathogenesis of this
      disease, and tyrosine hydroxylase (TH) is the rate-limiting enzyme in the
      synthesis of these two catecholamines. As TH mutations could underlie
      susceptibility to manic-depression, we carried out a linkage analysis between
      this disease in 8 families and two RFLP probes that map to the TH gene region on
      the short arm of chromosome 11. Evidence of linkage was not found in 7 of 8
      kindreds.

PMID- 1355074
TI  - Uptake of [3H]serotonin and [3H]glutamate by primary astrocyte cultures. I.
      Effects of different sera and time in culture.
AB  - Na(+)-dependent, fluoxetine-sensitive high-affinity uptake of serotonin and Na(+)
      dependent uptake of glutamate were studied in primary astrocyte cultures from 1
      day-old rat neocortex. This uptake was independent of time in culture from 1 to 6
      weeks. High-affinity serotonin uptake was decreased when cells were grown in
      horse serum as compared to fetal bovine serum and was almost absent when cells
      were grown in chemically defined medium. In contrast, glutamate uptake was
      unaffected by the composition of the medium in which the cultures were grown. The
      serum effect on serotonin uptake was not due to the greater level of serotonin in
      the fetal bovine serum and was only reversed by a change of serum over a time
      period of days.

PMID- 1355075
TI  - Uptake of [3H]serotonin and [3H]glutamate by primary astrocyte cultures. II.
      Differences in cultures prepared from different brain regions.
AB  - Regional astrocyte cultures were derived by dissecting six regions; brain stem,
      cerebellum, mesencephalon, basal ganglia plus diencephalon, cerebral cortex, and
      hippocampus, from 3 to 4-day-old neonatal rat brains. Glial fibrillary acidic
      protein (GFAP) immunocytochemistry was used to confirm the astrocyte composition
      of the cultures. The percentage of GFAP (+) cells between regions varied from 75%
      to 100%. Once confluent these cultures were incubated with radiolabeled serotonin
      or glutamate for uptake and autoradiographic studies. For the different brain
      regions Na(+)-dependent, [3H] L-glutamate, and fluoxetine-sensitive [3H] 5-HT
      uptake varied markedly. The relative order of uptake for [3H] 5-HT was MS
      (mesencephalon) greater than CC (cerebral cortex) greater than BG + DI (basal
      ganglia + diencephalon) greater than HP (hippocampus) greater than BS (brain
      stem) greater than CB (cerebellum). For [3H] L-glutamate the order was HP greater
      than CC greater than BG + DI greater than MS = BS greater than CB. For [3H] 5-HT
      this essentially corresponds to the reported order of binding in situ of the [3H]
      5-HT-specific uptake ligand [3H] citalopram. For [3H] L-glutamate regional
      variation of the uptake for the different cultures corresponds to the regional
      uptake reported for different regions of rat brain. Double-label studies with
      GFAP and radiolabeled neurotransmitters were also used to study uptake into
      GFAP(+) astrocytes by autoradiography. Flat GFAP cells with or without processes
      comprised 65-98% of the cultures and represented most of the uptake. The
      percentage of all GFAP(+) cells that were positive for uptake of ARG varied from
      50% to 90% and also showed differences in grain density both intra- and inter
      regionally. These differences in transmitter uptake by GFAP(+) astrocytes in
      primary culture, which are dependent on the region of origin and correspond to
      regional differences in situ, suggest that such uptake in vitro may reflect
      uptake by astrocytes in vivo. Implied in this is that uptake by astrocytes
      represents a significant component of serotonin uptake in vivo.

PMID- 1355076
TI  - Immunopathophysiology of gastrointestinal disease in HIV infection.
AB  - In summary, gastrointestinal manifestations are a major complication of HIV
      infection. These manifestations present clinically as early, intermediate, and
      late-phase enteric illness due to HIV itself or the acquisition of opportunistic
      infections and neoplasms. HIV-induced defects in lymphocytes and mononuclear
      phagocytes, which circulate through and populate the gastrointestinal mucosa, and
      a sequence of HIV-dependent alterations in mucosal integrity represent the
      fundamental immunopathophysiologic basis for these clinical manifestations.

PMID- 1355077
TI  - Cell-mediated immune injury in the intestine.
AB  - Epithelial adaptation clearly occurs during the course of intestinal cell
      mediated immune responses to alloantigens. The adaptive response is similar to
      that seen in a number of enteropathies, namely villus atrophy, crypt hypertrophy,
      and crypt cell hyperplasia. In human fetal gut, polyclonal activation of lamina
      propria CD4+ T cells produces the same epithelial adaptive responses. Although
      these data provide overwhelming evidence that cell-mediated immune responses can
      cause enteropathy, the demonstration of antigen-specific T cells in the lamina
      propria of patients with enteropathy is still lacking, even in a disease as well
      characterized as celiac disease. Epithelial adaptation in experimental and
      clinical situations, however, must involve a change in the mechanisms and
      mediators involved in normal intestinal homeostasis, such as epidermal growth
      factor and transforming growth factor-alpha and -beta, and in the interactions
      between epithelial cells and the underlying stromal cells.

PMID- 1355079
TI  - Proceedings of the 37th Congress of the International Psychoanalytical
      Association. Buenos Aires, 3 August 1991.

PMID- 1355078
TI  - Upregulation of adhesion molecules induced by broncho-vaxom on phagocytic cells.
AB  - Whole blood was incubated with the bacterial extract Broncho-Vaxom (OM85) at
      various concentrations and for different periods of time. Expression of the beta
      2-integrins (LFA-1, CD11a/CD18; MAC-1, CD11b/CD18; p150,95, CD11c/CD18) and ICAM
      1 (CD54) by monocytes and granulocytes was studied using flow cytometry. OM85
      enhanced the expression of MAC-1 and ICAM-1 on monocytes and granulocytes in a
      dose-dependent manner. Maximal expression was achieved with 1 mg/ml bacterial
      extract. The effect on MAC-1 expression was not due to the low concentration of
      endotoxin contaminating the preparation (less than 1 ng/mg) since polymyxin-B did
      not substantially affect the adhesion molecule upregulation induced by OM85. In
      addition, OM85 enhanced the expression of p150,95 on monocytes and granulocytes,
      and also increased expression of LFA-1 on monocytes, but not on granulocytes.
      While MAC-1 and p150,95 expression reached peak values between 1 and 6 h, levels
      of ICAM-1 rose constantly for 10 h. We suggest that the clinical interest of OM85
      in the management of recurrent infections could be related to be upregulation of
      adhesion molecules induced by this bacterial extract.

PMID- 1355080
TI  - Abstracts of the 9th International Congress of Histochemistry and Cytochemistry.
      Maastricht, The Netherlands, 30 August-5 September, 1992.

PMID- 1355081
TI  - Treatment of seminoma arising in cryptorchid testes.
AB  - We reviewed the clinical characteristics, treatment methods, and outcome of 26
      patients presenting with seminoma arising in an undescended testis. The tumor
      bearing testis was located in the iliac fossa in 17 patients and in the inguinal
      canal in nine. The most common presenting symptoms were pain or an enlarging
      mass. At diagnosis, the tumors tended to be relatively advanced, and 16 of 26
      patients (62%) had nodal metastases. In addition to the paraaortic nodes,
      metastases were frequent to the ipsilateral iliac and inguinal nodes even in the
      absence of prior inguinal-scrotal surgery. Four patients had documented pelvic
      peritoneal tumor seeding. All patients received treatment in addition to
      resection of the primary tumor. Fifteen patients received radiotherapy only, 10
      received chemotherapy only, and one received both modalities. At a median follow
      up of 9.6 years, only one patient had relapsed. He was initially treated with
      radiation and after relapse was successfully salvaged with chemotherapy. The 5
      and 10-year disease-free rate was 96%, and the 5 and 10-year survival rates were
      92% and 79%, respectively. Appropriate treatment of seminoma arising in an
      undescended testis results in an excellent outcome equivalent to that observed
      for the more usual scrotal seminomas.

PMID- 1355082
TI  - Role of the major pneumococcal autolysin in the atypical response of a clinical
      isolate of Streptococcus pneumoniae.
AB  - The autolytic enzyme (an N-acetylmuramyl-L-alanine amidase) of a clinical
      isolate, strain 101/87, which is classified as an atypical pneumococcus, has been
      studied for the first time. The lytA101 gene coding for this amidase (LYTA101)
      has been cloned, sequenced, and expressed in Escherichia coli. The LYTA101
      amidase has been purified and shown to be similar to the main autolytic enzyme
      (LYTA) present in the wild-type strain of Streptococcus pneumoniae, although it
      exhibits a lower specific activity, a higher sensitivity to inhibition by free
      choline, and a modified thermosensitivity with respect to LYTA. Most important,
      in contrast with the LYTA amidase, the activity of the LYTA101 amidase was
      inhibited by sodium deoxycholate. This property is most probably responsible of
      the deoxycholate-insensitive phenotype shown by strain 101/87. Phenotypic curing
      of strain 101/87 by externally adding purified LYTA or LYTA101 amidase restored
      in this strain some typical characteristics of the wild-type strain of
      pneumococcus (e.g., formation of diplo cells and sensitization to lysis by sodium
      deoxycholate), although the amount of the LYTA101 amidase required to restore
      these properties was much higher than in the case of the LYTA amidase. Our
      results indicate that modifications in the primary structure or in the mechanisms
      that control the activity of cell wall lytic enzymes seem to be responsible for
      the characteristics exhibited by some strains of S. pneumoniae that have been
      classically misclassified and should be now considered atypical pneumococcal
      strains.

PMID- 1355084
TI  - Characterization, localization, and sequence of F transfer region products: the
      pilus assembly gene product TraW and a new product, TrbI.
AB  - The traW gene of the Escherichia coli K-12 sex factor, F, encodes one of the
      numerous proteins required for conjugative transfer of this plasmid. We have
      found that the nucleotide sequence of traW encodes a 210-amino-acid, 23,610-Da
      polypeptide with a characteristic amino-terminal signal peptide sequence; in DNA
      from the F lac traW546 amber mutant, the traW open reading frame is interrupted
      at codon 141. Studies of traW expression in maxicells in the presence and absence
      of ethanol demonstrate that the traW product does undergo signal sequence
      processing. Cell fractionation experiments additionally demonstrated that mature
      TraW is a periplasmic protein. Electron microscopy also showed that F lac traW546
      hosts do not express F pili, confirming that TraW is required for F-pilus
      assembly. Our nucleotide sequence also revealed the existence of an additional
      gene, trbI, located between traC and traW. The trbI gene encodes a 128-amino-acid
      polypeptide which could be identified as a 14-kDa protein product. Fractionation
      experiments demonstrated that TrbI is an intrinsic inner-membrane protein. Hosts
      carrying the pOX38-trbI::kan insertion mutant plasmids that we constructed
      remained quite transfer proficient but exhibited increased resistance to F-pilus
      specific phages. Mutant plasmids pOX38-trbI472 and pOX38-trbI473 expressed very
      long F pili, suggestive of a pilus retraction deficiency. Expression of an excess
      of TrbI in hosts carrying a wild-type pOX38 plasmid also caused F-pilus-specific
      phage resistance. The possibility that TrbI influences the kinetics of pilus
      outgrowth and/or retraction is discussed.

PMID- 1355083
TI  - EJ-1, a temperate bacteriophage of Streptococcus pneumoniae with a Myoviridae
      morphotype.
AB  - The first temperate bacteriophage (EJ-1) of Streptococcus pneumoniae with
      Myoviridae morphotype A1 isolated from a clinical atypical strain has been
      purified and characterized. This phage has a double-stranded linear genome about
      42 kb long, but in contrast to the other pneumococcal temperate phages that have
      been characterized so far, EJ-1 does not contain any protein covalently linked to
      it. We have sequenced a fragment of EJ-1 DNA containing the ejl gene, encoding a
      cell wall lytic enzyme (EJL amidase). This gene has been cloned and expressed in
      Escherichia coli, and the EJL enzyme was purified and biochemically characterized
      as an N-acetylmuramyl-L-alanine amidase that shares many similarities with the
      major pneumococcal autolysin. The EJL amidase is a choline-dependent enzyme that
      needs the process of conversion to achieve full enzymatic activity, but in
      contrast to the wild-type pneumococcal LYTA amidase, this process was found to be
      reversible. Comparisons of the primary structure of this new lytic enzyme with
      that of the other cell wall lytic enzymes of S. pneumoniae and its bacteriophages
      characterized so far provided new insights as to the evolutionary relationships
      between phages and bacteria. The nucleotide sequences of the attachment site
      (attP) on the phage genome and one of the junctions created by the insertion of
      the prophage were determined. Interestingly, the attP site was located near the
      ejl gene, as previously observed for the pneumococcal temperate bacteriophage HB
      3 (A. Romero, R. Lopez, and P. Garcia, J. Virol. 66:2860-2864, 1992). A stem-and
      loop structure, some adjacent direct and inverted repeats, and two putative
      integration host factor-binding sites were found in the att sites.

PMID- 1355086
TI  - The dedB (usg) open reading frame of Escherichia coli encodes a subunit of acetyl
      coenzyme A carboxylase.

PMID- 1355085
TI  - Cloning and linkage analysis of Neisseria gonorrhoeae DNA methyltransferases.
AB  - We have cloned DNA methyltransferases (MTases) from various strains of Neisseria
      gonorrhoeae. Each of these clones represents a single specificity, indicating
      that the multiple gonococcal MTase specificities are encoded by monospecific
      MTases. The DNAs of five strains (FA5100, F62, MS11, Pgh3-2, and WR302) were
      digested with NheI, SpeI, or NheI plus SpeI and subjected to pulsed-field gel
      electrophoresis. The DNA MTase clones were used to probe Southern blots of these
      pulsed-field gels to determine whether the MTase genes are linked and whether
      there are strain-to-strain differences. The results indicate that none of these
      genes are closely linked, but variable hybridization patterns indicate that there
      exist restriction fragment length polymorphisms between the strains tested. Most
      of the chromosomal regions containing these restriction fragment length
      polymorphisms are clustered in regions containing gonococcal genes known or
      suspected to antigenically vary via genetic recombination.

PMID- 1355087
TI  - Physical map location of the new Escherichia coli gene sbm.

PMID- 1355088
TI  - Interaction of GroE with an all-beta-protein.
AB  - Molecular chaperones are involved in protein folding both in vivo and in vitro.
      The Escherichia coli chaperone GroEL interacts with a number of nonnative
      proteins. A common structural motif of nonnative proteins, which is recognized by
      GroEL, has not yet been identified. In order to study the role of beta-sheet
      secondary structure on the interaction of nonnative proteins with GroEL, we used
      the F(ab) fragment of a monoclonal antibody as a model substrate protein. Here we
      show that GroEL interacts functionally with this all-beta-protein during
      reactivation. Antibody fragments refold spontaneously in good yield from the
      guanidine-denatured state. Functional refolding to the native state is inhibited
      transiently by GroEL, but there is no complete folding arrest in the absence of
      Mg-ATP and GroES. The yield of these unspecifically released GroEL-bound F(ab)
      fragments corresponds to that of the spontaneous reactivation in the absence of
      chaperones. However, the refolding kinetics in the presence of GroEL are
      considerably slower. The addition of Mg-ATP to the GroEL.F(ab) complex results in
      an immediate release of bound substrate protein and a significant increase in the
      amount of reconstituted antibody fragments compared to spontaneous reactivation.
      GroES is not essential for functional GroEL-mediated refolding of the F(ab)
      fragment but affects the reactivation yield to a small extent. Interestingly,
      stimulation of the GroEL-mediated F(ab) refolding depends primarily on the
      binding and not on hydrolysis of adenosine triphosphates. Previous results
      indicate the binding of alpha-helices to GroEL. The results presented in this
      paper suggest that beta-sheet secondary structural elements are recognized by
      GroEL. We therefore conclude that the interaction of a nonnative protein with
      GroEL depends mainly on the nature of the early folding intermediate but not on a
      specific element of secondary structure.

PMID- 1355089
TI  - The genes encoding the two carboxyltransferase subunits of Escherichia coli
      acetyl-CoA carboxylase.
AB  - We report characterization of the component proteins and molecular cloning of the
      genes encoding the two subunits of the carboxyltransferase component of the
      Escherichia coli acetyl-CoA carboxylase. Peptide mapping of the purified enzyme
      component indicates that the carboxyltransferase component is a complex of two
      nonidentical subunits, a 35-kDa alpha subunit and a 33-kDa beta subunit. The
      alpha subunit gene encodes a protein of 319 residues and is located immediately
      downstream of the polC gene (min 4.3 of the E. coli genetic map). The deduced
      amino acid composition, molecular mass, and amino acid sequence match those
      determined for the purified alpha subunit. Six sequenced internal peptides also
      match the deduced sequence. The amino-terminal sequence of the beta subunit was
      found within a previously identified open reading frame of unknown function
      called dedB and usg (min 50 of the E. coli genetic map) which encodes a protein
      of 304 residues. Comparative peptide mapping also indicates that the dedB/usg
      gene encodes the beta subunit. Moreover, the deduced molecular mass and amino
      acid composition of the dedB/usg-encoded protein closely match those determined
      for the beta subunit. The deduced amino acid sequences of alpha and beta subunits
      show marked sequence similarities to the COOH-terminal half and the NH2-terminal
      halves, respectively, of the rat propionyl-CoA carboxylase, a biotin-dependent
      carboxylase that catalyzes a similar carboxyltransferase reaction reaction.
      Several conserved regions which may function as CoA-binding sites are noted.

PMID- 1355091
TI  - Orthostatic hypotension occurs following alpha 2-adrenoceptor blockade in chronic
      prazosin-pretreated conscious spontaneously hypertensive rats.
AB  - 1. Studies were performed to evaluate whether chronic prazosin treatment alters
      the alpha 2-adrenoceptor function for orthostatic control of arterial blood
      pressure in conscious spontaneously hypertensive rats (SHR). 2. Conscious SHR
      (male 300-350 g) were subjected to 90 degrees head-up tilts for 60 s following
      acute administration of prazosin (0.1 mg kg-1 i.p.) or rauwolscine (3 mg kg-1
      i.v.). Orthostatic hypotension was determined by the average decrease (%) in mean
      arterial pressure (MAP femoral) over the 60-s tilt period. The basal MAP of
      conscious SHR was reduced to a similar extent by prazosin (-23%(-)-26% MAP) and
      rauwolscine (-16%(-)-33% MAP). However, the head-up tilt induced orthostatic
      hypotension in the SHR treated with prazosin (-16% MAP, n = 6), but not in the
      SHR treated with rauwolscine (less than +2% MAP, n = 6). 3. Conscious SHR were
      treated for 4 days with prazosin at 2 mg kg-1 day-1 i.p. for chronic alpha 1
      adrenoceptor blockade. MAP in conscious SHR after chronic prazosin treatment was
      14% lower than in the untreated SHR (n = 8). Head-up tilts in these rats did not
      produce orthostatic hypotension when performed either prior to or after acute
      dosing of prazosin (0.1 mg kg-1 i.p.). Conversely, administration of rauwolscine
      (3 mg kg-1 i.v.) in chronic prazosin treated SHR decreased the basal MAP by 12
      31% (n = 4), and subsequent tilts induced further drops of MAP by 19-23% in these
      rats. 4. The pressor responses and bradycardia to the alpha 1-agonist cirazoline
      (0.6 and 2 micrograms kg-1 i.v.), the alpha 2-agonist Abbott-53693 (1 and 3
      micrograms kg-1 i.v.), and noradrenaline (0.1 and 1.0 micrograms kg-1 i.v.) were
      determined in conscious SHR with and without chronic prazosin pretreatment. Both
      the pressor and bradycardia effects of cirazoline were abolished in chronic
      prazosin treated SHR (n = 4) as compared to the untreated SHR (n = 4). On the
      other hand, the pressor effects of Abbott-53693 were similar in both groups of
      SHR, but the accompanying bradycardia was greater in SHR with chronic prazosin
      treatment than without such treatment. Furthermore, the bradycardia that
      accompanied the noradrenaline-induced pressor effect in SHR was similar with and
      without chronic prazosin treatment despite a 47-71% reduction of the pressor
      effect in chronic alpha 1-receptor blocked SHR.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1355090
TI  - An oncogenic point mutation confers high affinity ligand binding to the neu
      receptor. Implications for the generation of site heterogeneity.
AB  - The neu protooncogene encodes a receptor tyrosine kinase homologous to the
      receptor for the epidermal growth factor. The oncogenic potential of neu is
      released upon chemical carcinogenesis, which replaces a glutamic acid for a
      valine residue, within the single transmembrane domain. This results in
      constitutive receptor dimerization and activation of the intrinsic catalytic
      function. To study the implications of the oncogenic mutation and the consequent
      receptor dimerization on the interaction with the yet incompletely characterized
      ligand of p185neu, we constructed chimeric proteins between the ligand binding
      domain of the epidermal growth factor receptor and the transmembrane and
      cytoplasmic domains of the normal or the transforming Neu proteins. The chimeric
      receptors displayed cellular and biochemical differences characteristic of the
      normal and the transforming Neu proteins and therefore may reliably represent the
      ligand binding functions of the two receptor forms. Analyses of ligand binding
      revealed qualitative and quantitative differences that were a result of the
      single mutation; whereas the normal chimera (valine version) displayed two
      populations of binding sites with approximately 90% of the receptors in the low
      affinity state, the transforming receptor (glutamic acid version) showed a single
      population of binding sites with relatively high affinity. Kinetics measurements
      indicated that the difference in affinities was because of slower rates of both
      ligand association and ligand dissociation from the constitutively dimerized
      mutant receptor. It therefore appears that the oncogenic mutation, by permanently
      dimerizing the receptor, establishes a high affinity ligand binding state which
      is functionally equivalent to the ligand-occupied normal receptor. Our conclusion
      is further supported by the rates of endocytosis of the wild-type and the mutant
      receptor. Hence, these results provide the first experimental evidence from
      living cells which supports a model that attributes the heterogeneity of ligand
      binding sites to the state of oligomerization of receptor tyrosine kinases.

PMID- 1355092
TI  - Mechanical and biochemical effects of individual co-transmitters in rat tail
      arteries.
AB  - 1. The effects of (1) nerve stimulation (NS, 0.5 ms, 1-16 Hz, supramaximal
      voltage, 20 s) upon vasoconstriction, as measured by changes in perfusion
      pressure and (2) exogenously added co-transmitters noradrenaline (NA) and alpha,
      beta,-methylene ATP (alpha, beta, MeATP) upon polyphosphoinositide (PPI)
      breakdown, and vasoconstriction, were studied in rat tail perfused arteries or
      arterial rings. The interaction between NA and ATP upon contraction of artery
      rings and inositol phosphate (IP) accumulation was also studied. 2. Nerve
      stimulation evoked vasoconstriction in rat tail arteries. These pressor responses
      were largely (approximately 80%) blocked by the alpha 1-adrenoceptor antagonist,
      prazosin (10(-6) M), but not significantly affected by desensitization of P2x
      purinoceptors by prior, repeated (five times) addition of alpha, beta, MeATP (10(
      6) M). 3. Noradrenaline evoked a prazosin (10(-6) M)-sensitive, concentration
      dependent, increase in both perfusion pressure and total inositol phosphate (IP)
      accumulation over the same concentration range (10(-6)-10(-4) M). The amplitude
      of the pressor responses to NA were about 80% of those obtained to nerve
      stimulation (0.5 ms, 1-16HZ 20s supramaximal voltage). 4. alpha, beta,-methylene
      ATP (10(-7)-10(-5) M) evoked a concentration-dependent increase in perfusion
      pressure which, at maximum, was equivalent in amplitude to approximately 20% of
      that obtained to nerve stimulation. Concentrations of the nucleotide greater than
      10(-5) M were required to stimulate total IP accumulation. 5. The effects of NA
      (10(-6) M) and alpha, beta, MeATP (10(-5) M) upon contraction of artery rings and
      IP accumulation were additive and no evidence of synergism between them, on
      either parameter, was obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355093
TI  - Acetylcholine-induced relaxation of the rabbit aorta is preload-independent but
      markedly dependent upon the degree of excitatory agonist-induced tone.
AB  - 1. The aim of the present study was to investigate the relationship between
      endothelium-dependent relaxation evoked by acetylcholine, tissue preload and the
      degree of noradrenaline-induced tone in the isolated rabbit aorta. 2. In the
      aorta preload-response curves were bell-shaped with increasing preload augmenting
      responses to noradrenaline up to a certain point (optimal value) and then
      declining. Removal of the endothelium significantly increased responses to low
      concentrations of noradrenaline (less than 0.1 microM) but did not significantly
      affect the maximum response of the aorta to this amine or the preload-response
      curves generated at several concentrations of noradrenaline. 3. The optimal
      preload value was around 10 g for the aorta and changes in preload did not
      influence the sensitivity of the tissue to noradrenaline as assessed by pEC50
      values to this agonist. 4. Acetylcholine (0.01-10 microM) evoked endothelium
      dependent relaxations which in absolute terms increased as the tissue preload was
      increased. This relationship was much less evident when acetylcholine responses
      were measured in terms of the percentage inhibition of the respective
      noradrenaline contraction, when little or no change in the acetylcholine
      responses was noted. 5. When acetylcholine relaxations were expressed in terms of
      a percentage of the maximum noradrenaline-induced response evoked at each preload
      setting, the results confirmed that preload changes had little or no influence
      upon acetylcholine responses. 6. In contrast, tissue sensitivity to, and the
      extent of acetylcholine-induced relaxation, were markedly affected by the level
      of excitatory agonist-induced tone. As noradrenaline-induced tone increased,
      maximum responses and pIC50 values to acetylcholine were reduced.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1355094
TI  - Effect of the optical isomers of YM-12617 on increased intra-urethral pressure
      induced by phenylephrine in anaesthetized dogs.
AB  - 1. Effects of the individual optical isomers of YM-12617 (R, S 5-[2-[[2-(o
      ethoxyphenoxy)ethyl]-amino]propyl]-2- methoxybenzenesulphonamide HCl, (+/-)-YM),
      a potent selective alpha 1-adrenoceptor antagonist, on the increase in
      intraurethral pressure (IUP) and diastolic blood pressure (DBP) induced by
      phenylephrine were evaluated in pentobarbital-anaesthetized female dogs. 2.
      Phenylephrine (0.1-30 micrograms kg-1 i.v.), an alpha 1-adrenoceptor agonist,
      dose-dependently increased IUP and DBP. 3. alpha-adrenoceptor antagonists (i.v.)
      dose-dependently antagonized the increase in IUP and DBP induced by
      phenylephrine, with a potency ranking of R(-)-YM greater than (+/-)-YM greater
      than prazosin greater than phentolamine greater than S(+)-YM greater than
      yohimbine. 4. These results suggest that the alpha 1-adrenoceptor mediates the
      increase in IUP as well as DBP in anaesthetized dogs, and that alpha 1
      adrenoceptors in the urethra and arteries show a stereochemical preference for R(
      )-YM.

PMID- 1355096
TI  - Recognition of heterogeneous lymphokine-activated killer (LAK) receptors on
      Kaposi's sarcoma cells, endothelial cells, and monocytes/macrophages: evidence of
      distinct LAK-cell antigen on Kaposi's sarcoma cells--potential for use of LAK
      cells for immunotherapy.
AB  - The purpose of this study was to determine the potential use of lymphokine
      activated killer (LAK) cells against Kaposi's sarcoma (KS) cells. We used
      chromium release cold-target inhibition assay for understanding the expression of
      heterogeneous LAK-cell antigens (Ags) on KS cells, endothelial cells (ECs), and
      monocytes/macrophages (M phi) which could allow for the utilization of LAK-cell
      immunotherapy in KS without side effects. Our data show that (i) all three cell
      types express the CD18 Ag of LFA-1 or Leu-CAM, (ii) rare KS cells from eyes
      cannot cold target-inhibit ECs, (iii) KS cells express a distinct LAK-cell Ag,
      which we have called LAK-KS Ag, and (iv) LAK-KS Ag allows for cold-target
      inhibition between different KS cells. The identification of LAK-KS Ag and a
      monoclonal antibody capable of inhibiting lysis of ECs and M phi without
      obstructing LAK-KS Ag would be important.

PMID- 1355095
TI  - Association of intercellular adhesion molecule-1 (ICAM-1) with actin-containing
      cytoskeleton and alpha-actinin.
AB  - We have studied the cytoskeletal association of intercellular adhesion molecule-1
      (ICAM-1, CD54), an integral membrane protein that functions as a counterreceptor
      for leukocyte integrins (CD11/CD18). A linkage between ICAM-1 and cytoskeletal
      elements was suggested by studies showing a different ICAM-1 staining pattern for
      COS cells transfected with wild-type ICAM-1 or with an ICAM-1 construct that
      replaces the cytoplasmic and transmembrane domains of ICAM-1 with a
      glycophosphatidylinositol (GPI) anchor. Wild-type ICAM-1 appeared to localize
      most prominently in microvilli whereas GPI-ICAM-1 demonstrated a uniform cell
      surface distribution. Disruption of microfilaments with cytochalasin B (CCB)
      changed the localization of wild-type ICAM-1 but had no effect on GPI-ICAM-1.
      Some B-cell lines demonstrated a prominent accumulation of ICAM-1 into the uropod
      region whereas other cell surface proteins examined were not preferentially
      localized. CCB also induced redistribution of ICAM-1 in these cells. For
      characterization of cytoskeletal proteins interacting with ICAM-1, a 28-residue
      peptide that encompasses the entire predicted cytoplasmic domain (ICAM-1,478-505)
      was synthesized, coupled to Sepharose-4B, and used as an affinity matrix. One of
      the most predominant proteins eluted either with soluble ICAM-1,478-505-peptide
      or EDTA, was 100 kD, had a pI of 5.5, and in Western blots reacted with alpha
      actinin antibodies. A direct association between alpha-actinin and ICAM-1 was
      demonstrated by binding of purified alpha-actinin to ICAM-1,478-505-peptide and
      to immunoaffinity purified ICAM-1 and by a strict colocalization of ICAM-1 with
      alpha-actinin, but not with the cytoskeletal proteins talin, tensin, and
      vinculin. The region of ICAM-1,478-505 interacting with alpha-actinin was mapped
      to the area close to the membrane spanning region. This region contains several
      positively charged residues and appears to mediate a charged interaction with
      alpha-actinin which is not highly dependent on the order of the residues.

PMID- 1355097
TI  - The search for the genetic basis of aging: the identification of gerontogenes in
      the nematode Caenorhabditis elegans.
AB  - Study of C. elegans has provided much information for gerontologists. The
      influence of the genome on life span is clearly observable, and at least one
      gerontogene, age-1, has been defined. Data relating to important evolutionary
      questions has emerged and will continue to be used in testing current hypotheses.
      We are using an approach unbiased by theoretical constraints to delineate aging
      processes simultaneously at the molecular and organismal levels. Much remains to
      be discovered before fundamental questions posed in this article are answered to
      a satisfactory degree. The immediate agenda is the identification and isolation
      of gerontogenes which influence life span in invertebrate models. This work is
      well in hand and will lead to the unraveling of specific life-span-determining
      processes. At this point we may be able to predict whether analogous processes
      also limit life in mammals. If we are fortunate and aging processes exhibit
      evolutionary conservation, many exciting possibilities await. Molecular tools
      provided by the invertebrate system can then be used to isolate homologous
      mammalian gerontogenes that could be subsequently utilized in highly targeted
      attempts to intervene in mammalian aging. This offers the most direct strategy
      for identifying life-span prolongation genes in humans.

PMID- 1355098
TI  - Coexisting acromegaly and a unilateral cortisol-producing adrenal adenoma: a
      possible variant of multiple endocrine neoplasia type I.
AB  - An unusual case of coexisting acromegaly and Cushing's syndrome is reported in a
      34-yr-old female. There was no biochemical or morphological evidence to suggest
      the presence of other endocrinopathies. She did not have any family history to
      suggest a hereditary tendency to endocrine disorders. Her acromegaly and
      Cushing's syndrome were proven to be due to a pituitary somatotroph adenoma and a
      cortisol-producing adenoma in the right adrenocortex, respectively. Surgical
      removal of both tumors led to a marked biochemical improvement of the two
      endocrinopathies. To account for the simultaneous occurrence of the two endocrine
      tumors, at least two endocrine syndromes may be considered. One of them is
      Carney's complex. However, Cushing's syndrome in this complex is unexceptionally
      due to primary pigmented nodular adrenocortical disease, differing from the
      adrenal pathology of our patient. In addition, a lack in this case of any other
      characteristic suggestive of this syndrome appears to speak against this
      possibility. A second possibility is multiple endocrine neoplasia type 1. The
      absence of a parathyroid or pancreatic islet cell tumor does not strongly support
      this possibility, but adrenocortical lesions are not rare in this syndrome
      although they are only rarely functional. However, existence of similar case
      reports, although very few, in the literature leaves the possibility that she
      represents another rare variant of sporadic multiple endocrine neoplasia type I
      syndrome.

PMID- 1355099
TI  - Short-term retinoic acid treatment increases in vivo, but decreases in vitro,
      epidermal transglutaminase-K enzyme activity and immunoreactivity.
AB  - Epidermal transglutaminase-K is believed to catalyze the covalent linking of
      loricrin and involucrin to form cross-linked (CE) envelopes. In normal skin,
      transglutaminase-K is expressed as a band immediately below the stratum corneum,
      whereas in psoriasis and healing skin its expression is considerably expanded
      throughout the suprabasal layers. We have investigated whether the
      hyperproliferative state induced by short-term application of topical retinoic
      acid is similarly characterized by an increase in transglutaminase-K enzyme
      activity and immunoreactivity. Retinoic acid (0.1% cream) or vehicle were applied
      to human skin and occluded for 4 d. Skin biopsies were obtained for measurement
      of transglutaminase-K and transglutaminase-C activity and immunoreactivity. For
      comparison, cultured normal human keratinocytes were incubated for 4 d in the
      presence of 1 microM retinoic acid and the subsequent transglutaminase-K activity
      and immunoreactivity measured. Transglutaminase-K activity was increased 2.8
      times in retinoic acid compared to vehicle-treated skin (p less than 0.005, n =
      12) whereas there was no significant difference in transglutaminase-C activity.
      However, transglutaminase-K mRNA levels were not significantly different between
      retinoic acid- and vehicle-treated skin. In vehicle-treated skin,
      transglutaminase-K immunoreactivity was limited to a narrow, substratum corneal
      band, but was considerably expanded in a diffuse suprabasal pattern in retinoic
      acid-treated epidermis. In contrast, transglutaminase-K immunostaining was
      decreased and its enzymatic activity reduced sixfold in retinoic acid-treated
      keratinocytes (p less than 0.01, n = 4). These results demonstrate that retinoic
      acid treatment in vivo, in contrast to in vitro, leads to not only increased
      transglutaminase-K protein expression but also increased enzymatic activity in
      the absence of detectable increases in mRNA levels. These data, taken with the
      previously reported lack of in vivo modulation of the differentiation markers
      keratins 1 and 10 by retinoic acid, indicate that certain aspects of keratinocyte
      terminal differentiation that are altered in vitro by retinoic acid do not occur
      in vivo in human skin.

PMID- 1355100
TI  - [Oncogenes and tumor suppressor genes in the development of colonic tumors].

PMID- 1355101
TI  - [A case of microscopic polyarteritis nodosa complicated with severe pulmonary
      hemorrhage and subacute kidney failure].

PMID- 1355102
TI  - Lipoprotein lipase genotypes for a common premature termination codon mutation
      detected by PCR-mediated site-directed mutagenesis and restriction digestion.
AB  - We have developed a procedure for the determination of a common mutation in exon
      9 of the human lipoprotein lipase (LPL) gene. The mutation is due to a C-G
      transversion which creates a premature termination codon (Ser447-Ter) and results
      in a truncated LPL molecule lacking the C-terminal dipeptide SER-GLY. The
      mutation can be detected by polymerase chain reaction (PCR) amplification of exon
      9 using a modified 3' amplimer that produces a 140 bp product containing a site
      for the restriction enzyme Hinf-1 in the presence of the mutation (G allele). The
      G allele was in strong linkage disequilibrium with a Hind-III restriction
      fragment length polymorphism (RFLP) allele in intron 8. Genotype determinations
      for the mutation can be performed by PCR amplification of genomic DNA, digestion
      with Hinf-1, and analysis of the products by polyacrylamide gel electrophoresis.
      The allelic frequency of the Ser447-Ter mutation in normal male Caucasian
      controls was 0.11. The frequency of the mutation was lower in a group of subjects
      with primary hypertriglyceridemia compared to normolipidemic controls.

PMID- 1355103
TI  - Resolution of Pneumocystis carinii pneumonia in CD4+ lymphocyte-depleted mice
      given aerosols of heat-treated Escherichia coli.
AB  - Mice were thymectomized and depleted of CD4+ lymphocytes by treatment with
      monoclonal antibody to induce Pneumocystis carinii (PC) pneumonia (PCP). These
      mice were then exposed to aerosols of heat-treated Escherichia coli three times a
      week. Aerosol treatment for 10 d caused a slight reduction in numbers of PC
      nuclei in the lungs of mice, and treatment for 22 d resulted in nearly complete
      resolution of PCP. Large numbers of macrophages, polymorphonuclear leukocytes,
      and lymphocytes accumulated in lungs of aerosol-treated mice. Depletion of either
      CD8+ lymphocytes or asialo GM1+ cells that remained in the mice after CD4+ cell
      depletion had no effect on the ability of the mice to resolve PCP after E. coli
      aerosol treatments. However, depletion of Thy-1+ lymphocytes in these mice
      abrogated their ability to resolve PCP and reduced the numbers of macrophages
      that accumulated in the lungs. In addition, it was found that resolution of PCP
      induced by heat-treated E. coli aerosol treatments was also abrogated when mice
      were treated with polyclonal antibodies against tumor necrosis factor alpha (TNF
      alpha). Thus, resolution of PCP in CD4+ lymphocyte-depleted mice by heat-treated
      E. coli aerosols was not dependent on either CD8+ or asialo GM1+ cells but was
      dependent on Thy-1+CD4-CD8- lymphocytes and on the participation of TNF. These
      results indicate that heat-treated E. coli aerosols can act as an immune response
      modifier by inducing resolution of PCP in mice by a mechanism not dependent on
      the presence of CD4+ lymphocytes.

PMID- 1355104
TI  - CD4+8- thymocytes bearing major histocompatibility complex class I-restricted T
      cell receptors: evidence for homeostatic control of early stages of CD4/CD8
      lineage development.
AB  - During thymus development CD4+ CD8+ precursor cells differentiate into mature
      CD4+ and CD8+ T cells expressing T cell receptors (TCR) that recognize foreign
      antigens in association with major histocompatibility complex (MHC) class II or I
      molecules, respectively. Studies with TCR transgenic mice have shown that the
      accumulation of mature CD4+ and CD8+ thymocytes is strongly skewed by the MHC
      restriction specificity of the TCR, thus suggesting that commitment of CD4+ CD8+
      precursors to the CD4 or CD8 lineage is a direct consequence of TCR/MHC
      interactions. However, we show here that CD4+ cells expressing an inappropriate
      (MHC class I-specific) TCR appear transiently in the neonatal thymus of TCR
      transgenic mice and can also be found in the periphery of adult TCR transgenic
      recombination-deficient SCID mice. These data argue that the early stages of CD4
      and CD8 lineage development in the thymus are (at least in part) controlled by
      homeostatic mechanisms independent of appropriate TCR/MHC interactions.

PMID- 1355105
TI  - CD2-mediated autocrine growth of herpes virus saimiri-transformed human T
      lymphocytes.
AB  - Herpes virus saimiri (HVS) immortalizes T lymphocytes from a variety of primates
      and causes acute T cell lymphomas and leukemias in nonnatural primate hosts. Here
      we have analyzed the requirements for growth of three HVS-transformed human T
      cell lines. The cells expressed the phenotype of activated T cells: two were
      CD4+, and one was CD8+. All three cells responded to all allogeneic human cell
      lines tested with enhanced proliferation, production of interleukin 2 (IL-2), and
      increased expression of the IL-2 receptor. Binding of CD2 to its ligand CD58 was
      the critical event mediating stimulation because: (a) monoclonal antibodies
      (mAbs) to CD2 and to CD58, but not to a variety of other surface structures,
      blocked induced and spontaneous proliferation and IL-2 production; (b) only anti
      CD2 mAbs were stimulatory if crosslinked; (c) a nonstimulatory cell was rendered
      stimulatory by CD58 transfection; and (d) the cells responded specifically to
      CD58 on sheep red blood cells. Growth of the cells required activation because
      cyclosporin A and FK506 blocked stimulator cell-induced IL-2 production and
      proliferation as well as the spontaneous growth of the lines. Antibodies to the
      IL-2 receptor reduced proliferation of the cells and blocked IL-2 utilization.
      Taken together, these results show that HVS-transformed T cells proliferate in
      response to CD2-mediated contact with stimulator cells or with each other in an
      IL-2-dependent fashion. They suggest that HVS transforms human T cells to an
      activation-dependent autocrine growth.

PMID- 1355106
TI  - Modulation of rabbit ventricular cell volume and Na+/K+/2Cl- cotransport by cGMP
      and atrial natriuretic factor.
AB  - Previously we showed that atrial natriuretic factor (ANF) decreases cardiac cell
      volume by inhibiting ion uptake by Na+/K+/2Cl- cotransport. Digital video
      microscopy was used to study the role of guanosine 3',5'-monophosphate (cGMP) in
      this process in rabbit ventricular myocytes. Each cell served as its own control,
      and relative cell volumes (volume(test)/volume(control)) were determined.
      Exposure to 10 microM 8-bromo-cGMP (8-Br-cGMP) reversibly decreased cell volume
      to 0.892 +/- 0.007; the ED50 was 0.77 +/- 0.33 microM. Activating guanylate
      cyclase with 100 microM sodium nitroprusside also decreased cell volume to 0.889
      +/- 0.009. In contrast, 8-bromo-adenosine 3',5'-monophosphate (8-Br-AMP; 0.01-100
      microM) neither altered cell volume directly nor modified the response to 8-Br
      cGMP. The idea that cGMP decreases cell volume by inhibiting Na+/K+/2Cl-
      cotransport was tested by blocking the cotransporter with 10 microM bumetanide
      (BUM) and removing the transported ions. After BUM treatment, 10 microM 8-Br-cGMP
      failed to decrease cell volume. Replacement of Na+ with N-methyl-D-glucamine or
      Cl- with methanesulfonate also prevented 8-Br-cGMP from shrinking cells. The data
      suggest that 8-Br-cGMP, like ANF, decreases ventricular cell volume by inhibiting
      Na+/K+/2Cl-cotransport. Evidence that ANF modulates cell volume via cGMP was also
      obtained. Pretreatment with 10 microM 8-Br-cGMP prevented the effect of 1 microM
      ANF on cell volume, and ANF suppressed 8-Br-cGMP-induced cell shrinkage.
      Inhibiting guanylate cyclase with the quinolinedione LY83583 (10 microM)
      diminished ANF-induced cell shrinkage, and inhibiting cGMP-specific
      phosphodiesterase with M&B22948 (Zaprinast; 100 microM) amplified the volume
      decrease caused by a low dose of ANF (0.01 microM) approximately fivefold. In
      contrast, neither 100 microM 8-Br-cAMP nor 50 microM forskolin affected the
      response to ANF. The effects of ANF, LY83583, and M&B29948 on cGMP levels in
      isolated ventricular myocytes were confirmed by 125I-cGMP radioimmunoassay. These
      data argue that ANF shrinks cardiac cells by increasing intracellular cGMP,
      thereby inhibiting Na+/K+/2Cl- cotransport. Basal cGMP levels also appear to
      modulate cell volume.

PMID- 1355107
TI  - Dissociation by NH4Cl treatment of the enzymic activities of glutamine synthetase
      II from Rhizobium leguminosarum biovar viceae.
AB  - Glutamine synthetase II (GSII) was purified to homogeneity from Rhizobium
      leguminosarum biovar viceae and characterized. The sequence of 26 amino acid
      residues from the amino-terminal end of the protein showed high similarity with
      the sequence of GSII from Bradyrhizobium japonicum or from Rhizobium meliloti.
      Non-denaturing PAGE showed that GSII, either in crude extracts or in the pure
      state, was a mixture of an octamer and a tetramer and that under specific
      conditions the octamer/tetramer ratio could be modified in either direction. The
      pure enzyme was used to raise an antiserum which was highly specific. Addition of
      NH4Cl to a bacterial culture derepressed for GSII caused a specific decrease in
      transferase activity, faster than the one observed when the amount of
      immunoreactive material was measured by different methods. On the other hand,
      biosynthetic activity, measured as the rate of ADP or glutamine formation,
      paralleled the rate of decrease in immunoreactive material. A partially purified
      enzyme preparation retained this dissociation of kinetic parameters, strongly
      suggesting a post-translational modification. These findings are discussed with
      respect to the possible role of GSII in the Rhizobium-legume symbiosis.

PMID- 1355108
TI  - Molecular cloning of a determinant coding for fimbrial antigen F165(1), a Prs
      like fimbrial antigen from porcine septicaemic Escherichia coli.
AB  - The genetic determinant coding for F165(1) fimbriae was cloned from the
      chromosome of the porcine Escherichia coli wild-type strain 4787 (O115:K
      :H51:F165). The fimbrial determinant was further subcloned into the BamHI site of
      pACYC184 and a restriction map was established. On Southern hybridization,
      identity between the chromosomally encoded prs-like determinant of strain 4787
      and its cloned counterparts was demonstrated. The cloned F165(1) fimbriae and
      those of the wild-type strain possessed a major protein subunit of molecular mass
      18.5 kDa. Strains expressing F165(1) fimbriae were detected using an F165
      specific polyclonal antiserum and caused mannose-resistant haemagglutination and
      agglutination of Forssman latex beads. Antiserum against the cloned F165(1)
      fimbriae recognized a 18.5 kDa band in the parent strain 4787.

PMID- 1355109
TI  - Possible mechanisms underlying hyperexcitability in the epileptic mutant mouse
      tottering.
AB  - Tottering mice present a useful experimental model of genetically determined
      generalized epilepsy of the absence type. In electrophysiological recordings from
      hippocampal slices in vitro we found that the postsynaptic excitability (firing
      threshold) of pyramidal neurons in the CA1 area of tg/tg slices was significantly
      higher than that of normal slices. In spite of this hyperexcitability, in vitro
      epileptiform discharges were not observed spontaneously, or upon provocation by
      intracellular depolarizing pulses, or in response to moderate elevations (+2 mM)
      in extracellular potassium. The latter elevations actually induced significantly
      smaller increases in the CA1 synaptic responses of tg/tg as compared to normal
      slices. The hyperexcitability of tottering neurons could not be explained in
      terms of altered membrane electrical properties or any reduction of synaptic
      inhibition or increased capacity for long-term potentiation. Responses to
      noradrenaline, histamine and adenosine, as well as to the release of N-methyl-D
      aspartate channels--by eliminating Mg(2+)--were comparable in tg/tg and normal
      slices. These studies show that hyperexcitability can be co-inherited with
      epilepsy and in this model its expression can be maintained in vitro. The
      neuronal mechanism of this expression remains elusive, as it does not appear to
      include some features known to be shared by experimental models of chemically or
      electrically induced epilepsy.

PMID- 1355110
TI  - 1H- and 13C-nmr assignments for taxol, 7-epi-taxol, and cephalomannine.
AB  - The 1H- and 13C-nmr spectra of taxol [1], 7-epi-taxol [2], and cephalomannine [3]
      were assigned using modern 1D and 2D nmr methods. Preliminary conformational
      information was obtained by nOe spectroscopy.

PMID- 1355111
TI  - Effects of genetic, epigenetic, and environmental factors on taxol content in
      Taxus brevifolia and related species.
AB  - The demand for taxol, a promising cancer chemotherapeutic agent, far exceeds
      supply. Presently, taxol is derived from the bark of the Pacific yew, Taxus
      brevifolia, a small, slow-growing evergreen tree native to the northwestern
      United States. Knowledge of the distribution and magnitude of genetic and non
      genetic sources of variation in taxol content in the genus Taxus is necessary if
      supply issues are to be met through plant harvesting. Analytical determinations
      of taxol, cephalomannine, and baccatin III in more than 200 trees representing
      several populations of T. brevifolia and other yew taxa indicate that (1)
      significant variation in taxane content exists among and within populations and
      species, (2) taxol levels exceeding those reported for T. brevifolia bark were
      found in shoots of individual trees from most taxa studied, and (3) the season in
      which samples are collected and handling procedures can influence taxane content.

PMID- 1355112
TI  - Modulation of cell growth and host protein synthesis during HIV infection in
      vitro.
AB  - During HIV infection of CEM cells cultured in vitro, significant differences in
      growth rate and protein turnover were observed with different viral preparations.
      There was a significant inhibition of proliferation after infection with crude
      HIV supernatants. On the other hand, infection with purified HIV particles
      obtained by filtration, differential centrifugation, and isopycnic sedimentation
      led to a progressively increasing stimulation of cell growth. This early
      stimulation was prevented by neutralizing the virus with soluble CD4 molecules.
      Study of cell growth in the presence of a purified membrane preparation indicated
      that membrane fragments contaminating the crude HIV supernatant were responsible
      for the observed growth inhibition. Interestingly, the stimulation of
      proliferation was also observed with heat-inactivated virus or after inhibition
      of viral replication with ZDV. In the presence of purified HIV virions, the rate
      of general protein synthesis was not inhibited, as is usually observed with crude
      viral supernatants. However, a marked reduction in protein content and increased
      protein degradation was found in cultures infected with either crude or purified
      HIV preparations.

PMID- 1355113
TI  - Pattern of CD4+ T cell loss in HIV infection.

PMID- 1355114
TI  - Orthostatic hypotension: a potential side effect of psychiatric medications.
AB  - 1. Orthostatic hypotension is a major underrecognized side effect of
      antipsychotic and antidepressant medications. It has been associated with falls,
      fractures, and lacerations, particularly in the elderly. 2. Orthostatic vital
      signs need to be routinely measured in patients susceptible to orthostasis. A
      standardized procedure should be available and must include a stable baseline
      measurement in the supine position at 30 seconds and 2 minutes in the sitting or
      standing position. 3. Measures to counteract orthostasis include
      nutrition/hydration assessment, environmental safety, and patient teaching.

PMID- 1355115
TI  - Vitamin A intoxication during taxol therapy for refractory ovarian cancer.

PMID- 1355116
TI  - Dermatitis caused by dimethyl cyanocarbonimidodithioate.
AB  - Dimethyl cyanocarbonimidodithioate (CAS No. 10191-60-3) a raw material for
      cimetidine synthesis, is labelled as an irritant on its storage tank. There is no
      information available regarding the toxic effects of human exposure. We report a
      case of severe dermatitis clinically resembling erythema multiforme following an
      accidental exposure to dimethyl cyanocarbonimidodithioate in an occupational
      setting. A clerk sifted a handful of dimethyl cyanocarbonimidodithioate from an
      unlabelled bucket through his bare hands during an inspection prior to customs
      clearance. Five hours later, while he was washing his hands, pruritus, erythema
      and vesicles developed over the exposed area. The skin condition worsened within
      two weeks, extending to his whole body with generalized erythema and vesicles of
      various sizes. Some vesicles became confluent with ruptured bullae, resembling a
      second degree burn over 40% of the body. Elevation of the serum IgE (705 mu/mL,
      normal less than 300 mu/mL) and lymphocyte activation with an increased 3H
      thymidine uptake by the patient's mononuclear cells suggested that this episode
      resulted from a cell-mediated allergic skin reaction. The skin lesions improved
      progressively after systemic steroid therapy for about two weeks. Dimethyl
      cyanocarbonimidodithioate is used as a raw material for cimetidine synthesis by
      some pharmaceutical manufacturers. Our experience suggests that a severe reaction
      similar to that caused by another H2-blocker, ranitidine and its intermediate may
      be caused by dimethyl cyanocarbonimidodithioate in occupational exposures.
      Systemic steroid administration is beneficial in treatment.

PMID- 1355118
TI  - From the Centers for Disease Control. Availability of flow cytometric
      immunophenotyping of lymphocytes to hospital patients--United States.

PMID- 1355117
TI  - The cholinergic and purinergic components of detrusor contractility in a whole
      rabbit bladder model.
AB  - Whole rabbit bladders were suspended in a bath chamber and stimulated with ATP,
      bethanechol, electrical field stimulation, and bethanechol + ATP. Detrusor
      pressure and fluid expelled by the bladder were recorded, synchronized, and
      digitized. Detrusor work and power were calculated with a computer program.
      Maximum work was 61.4 +/- 28.7, 83.3 +/- 17.0, 85.0 +/- 15.0, 90.8 +/- 13.1 cm.
      H2O, ml. for ATP, bethanechol, electrical and bethanechol + ATP, respectively.
      Maximum power generated by ATP was 4.8 +/- 3.0 cm. H2O, ml./sec and was
      approximately 66% of that generated by bethanechol, and 50% of that generated by
      electrical stimulation, and bethanechol + ATP. ATP cannot empty the bladder with
      moderate outlet resistance while bethanechol and electrical stimulation can. Our
      results suggest that ATP is able to generate detrusor power and achieve work in
      bladder emptying. However, ATP generated power and work is considerably less than
      that of electrical stimulation or bethanechol alone. ATP mediated contraction is
      not inhibited by atropine or tetrodotoxin but is inhibited by P2 purinoceptor
      desensitization, suggesting a functional role of purine receptors on detrusor
      smooth muscle. Since ATP generated pressure is more rapid than with bethanechol
      alone, we support the hypothesis that ATP may be important in the initiation of
      micturition.

PMID- 1355119
TI  - [Management of hyperlipidemia caused by antihypertensive therapy].

PMID- 1355120
TI  - [Effect of antihypertensive drugs on glucose tolerance].

PMID- 1355121
TI  - [The management of hyperuricemia associated with drug treatment of hypertension].

PMID- 1355122
TI  - [Skin diseases caused by antihypertensive agents].

PMID- 1355123
TI  - [Treatment of hypertension associated with coronary artery disease].

PMID- 1355124
TI  - [Hypotensive therapy of hypertensive patients associated with renal impairment].

PMID- 1355125
TI  - [Treatment of hypertension in diabetic patients].

PMID- 1355126
TI  - [Interactions between antihypertensive drugs].

PMID- 1355127
TI  - [Pharmacological treatment of borderline hypertension].

PMID- 1355128
TI  - [Interactions between anti-hypertensive and non-antihypertensive drugs].

PMID- 1355130
TI  - [Pharmacological treatment of mild hypertension].

PMID- 1355129
TI  - [Mild hypertension: concept].

PMID- 1355131
TI  - [New antihypertensive drugs on various phases of study].

PMID- 1355132
TI  - [Hemorheology in geriatric patients with hypertension].

PMID- 1355133
TI  - [Pharmacological therapy of hypertension in the elderly].

PMID- 1355134
TI  - [Side effects and safety in drug therapy of hypertension].

PMID- 1355135
TI  - [Treatment of hypertension and quality of life in the elderly].

PMID- 1355136
TI  - [Assessment of the antihypertensive therapy with 24 ambulatory monitoring of
      blood pressure].

PMID- 1355137
TI  - [Tolerance and withdrawal syndrome].

PMID- 1355138
TI  - [Secondary hypertension due to glomerulonephritis].

PMID- 1355139
TI  - [Hypertension in dialysis patients].

PMID- 1355140
TI  - [Drug therapy of renovascular hypertension].

PMID- 1355141
TI  - [Hypertension secondary to aortoarteritis].

PMID- 1355142
TI  - [Selection and combined therapy of antihypertensive drugs].

PMID- 1355143
TI  - [Psychoneurotic dysfunctions as side effect of antihypertensive agents].

PMID- 1355144
TI  - [Cell proliferation kinetics in the rat gastric mucosa evaluated by
      immunohistochemical staining of PCNA--compared with immunohistochemical staining
      of BrdU].

PMID- 1355145
TI  - Immunosuppressive factors in porcine ciliary body.
AB  - Immunosuppressive factors locally present in the anterior tissues such as the
      ciliary body may contribute to the immunological privilege of the anterior
      chamber of the eye. Porcine ciliary body extracts contain at least three
      immunosuppressive factors (greater than 200 kDa, 25 kDa and 2.5 kDa) which can be
      separated by Sephacryl S300 gel filtration. On the basis of its molecular weight
      and reversal of inhibitory activity by anti-transforming growth factor beta (TGF
      beta) antibody, 25 kDa factor is identified with TGF beta. The high molecular
      factor is low in protein content and its activity is not affected by anti-TGF
      beta antibody. The 2.5 kDa factor is most likely to be identical with a low
      molecular factor present in the vitreous body and aqueous humor. This low
      molecular factor is extracted from nonpigmented ciliary epithelial cells but
      seems to be absent in the extracts of pigmented epithelial cells. The regional
      distribution suggests that the factor may be synthesized and secreted with the
      aqueous humor by the nonpigmented cells. All three factors suppress
      lymphoblastogenesis without affecting the expression of CD4 and CD8. Identical or
      similar factors may be present in other immunologically privileged tissues and be
      responsible for maintaining the immunologically suppressed environment.

PMID- 1355146
TI  - Neuroprotective effect of WEB 1881 FU (nebracetam) on an ischemia-induced deficit
      of glucose uptake in rat hippocampal and cerebral cortical slices and CA1 field
      potential in hippocampal slices.
AB  - Effect of WEB 1881 FU (nebracetam) on hypoxia and ischemia-induced impairment of
      2-deoxyglucose (2DG) uptake and CA1 field potentials induced by hypoxia and
      hypoxia/hypoglycemia (ischemia) in rat brain slices was evaluated and compared to
      the findings obtained with pentobarbital and idebenone. Hippocampal and cortical
      slices were exposed to 15-20 min of ischemia, and then these slices were returned
      to oxygenated and glucose-containing buffer for 6 hr. Ischemia reduced both 30 mM
      KCl-induced 2DG uptake and CA1 field potentials elicited by the stimulation of
      Schaffer collaterals in the hippocampus. Pretreatment of nebracetam at 1 mM or
      pentobarbital at 0.1 mM attenuated a decline of 2DG uptake and CA1 field
      potentials under the condition of ischemia. In addition, nebracetam and
      pentobarbital relatively recovered the increase of 2DG uptake in the hippocampus
      under hypoxia for 45 min. Furthermore, these drugs also attenuated the decline of
      2DG uptake induced by 10 mM glutamate for 20 min. However, treatment with
      idebenone did not recover the deficit of 2DG uptake and CA1 field potential. The
      present result suggests that nebracetam and pentobarbital exert neuroprotective
      actions against not only ischemia but also glutamate toxicity.

PMID- 1355147
TI  - Anticonflict action of tandospirone in a modified Geller-Seifter conflict test in
      rats.
AB  - Tandospirone is a novel non-benzodiazepine compound possessing potent anxiolytic
      properties in a water lick conflict paradigm in rats and a high affinity for
      central 5-HT1A receptors. In the present study, tandospirone was evaluated for
      anxiolytic activity in a modified Geller-Seifter conflict paradigm in rats.
      Tandospirone produced significant increases in the punished responding at doses
      of 1.25, 2.5 and 5.0 mg/kg, i.p. or 20 mg/kg, p.o., although it decreased
      unpunished responding at doses of 2.5 and 5.0 mg/kg, i.p. or 20 mg/kg, p.o.
      Likewise, diazepam was also effective after i.p.-administration in this test, and
      its minimum effective dose was slightly higher than that of tandospirone. This
      suggests that tandospirone might be as effective in the treatment of anxiety as
      diazepam. The anticonflict action of tandospirone was not inhibited by Ro-15
      1788, a benzodiazepine antagonist, although that of diazepam was completely
      inhibited. 8-OH-DPAT, a full agonist of 5-HT1A receptors, was also effective in
      this test with a high potency. Therefore, the possibility exists that the
      anticonflict action of tandospirone is related to its agonist action on 5-HT1A
      receptors, not on benzodiazepine receptors.

PMID- 1355148
TI  - Compliance and reactivity of the peripheral venous system in chronic intermittent
      hemodialysis.
AB  - A reduced venous compliance and/or inadequate venoconstriction could impair
      hemodynamics during hemodialysis. Therefore, compliance and reactivity of the
      peripheral venous system were assessed in hemodialysis patients and controls
      using strain gauge plethysmography. Reactivity of the venous system towards an
      efferent sympathetic stimulus was assessed using a cold pressor test. Results
      showed that venous compliance was reduced in hypertensive hemodialysis patients
      compared to normotensive dialysis patients (P = 0.013) and normotensive controls
      (P = 0.004). After one dosage with a directly acting venodilator (nitroglycerin 5
      mg s.l.) and 3 days of treatment with an alpha 1-sympathicolytic agent (Doxazosin
      2 mg), venous compliance remained unaltered in hypertensive dialysis patients.
      During the cold pressor test, the blood pressure response, rise in noradrenaline
      levels and decline in venous compliance were normal in hemodialysis patients.
      However, their response to the Valsalva manoeuver was significantly impaired (P =
      0.011) compared to healthy controls. We conclude that hypertension, not renal
      failure, causes the reduction of peripheral venous compliance in hemodialysis
      patients, for which structural factors might be responsible. Despite the
      existence of autonomous neuropathy, the reaction of the peripheral venous system
      towards an efferent sympathetic stimulus is intact in hemodialysis patients.

PMID- 1355149
TI  - Effects of ACE inhibition supplementary to beta blockers and diuretics in early
      diabetic nephropathy.
AB  - Angiotensin converting enzyme (ACE) inhibition has shown promising results in
      diabetic nephropathy, but long-term results on survival are not available. In a
      cohort of patients receiving antihypertensive treatment predominantly consisting
      of beta blockers in combination with diuretics, support for an improved survival
      has been presented. Addition of ACE inhibition to such a combination treatment
      may be favorable both due to the suggested renoprotective effects of ACE
      inhibitors and because diuretics activate the renin-angiotensin system. In 10
      insulin-dependent diabetic patients with early diabetic nephropathy [urinary
      albumin excretion rate (UAE) less than 100o micrograms/min], who were receiving
      continuous therapy with metoprolol and bendroflumethiazide, a double-blind
      crossover study with four months addition of ramipril 5 mg (Ramace) and placebo
      was conducted. UAE (radioimmunoassay) and fractional albumin excretion were
      significantly reduced after the four months of ramipril administration [UAE:
      114.1 x/divided by 1.3 (geometric mean x/divided by confidence factor] versus
      174.6 x/divided by 1.2 micrograms/min, 2P less than 0.005). Renal plasma flow
      (clearance of 131I-hippuran) tended to increase [497 +/- 25 (mean +/- SE) vs. 464
      +/- 28 ml/min/1.73 m2, 2P = 0.08], while GFR (125I-iothalamate) stayed unchanged
      (121 +/- 8 vs. 120 +/- 9 ml/min/1.73 m2). Mean arterial pressure during clearance
      studies fell moderately (95 +/- 3 vs. 101 +/- 1 mm Hg, 2P less than 0.05) and
      renal resistance was decreased (2P less than 0.03). ACE activity was suppressed
      in all patients. Twenty-four-hour ambulatory blood pressure measurements were not
      significantly different after the two periods (daytime averages: 91 +/- 2 vs. 93
      +/- 2, nighttime 80 +/- 2 vs. 84 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355150
TI  - Evidence of organ damage after cardiopulmonary bypass. The role of elastase and
      vasoactive mediators.
AB  - In this study the causes of organ damage after cardiopulmonary bypass were
      multifactorial. The concentration of the proteolytic enzyme elastase, which was
      released from activated granulocytes in the milieu of significantly reduced
      levels of alpha 1-protease inhibitor (p less than 0.01), increased during
      cardiopulmonary bypass (p less than 0.01). In addition, bypass initiated platelet
      aggregation, which both altered the eicosanoid metabolism and caused the level of
      thromboxane A2 to increase and surpass the level of prostaglandin I2. Because
      thromboxane A2 dominance subsided immediately after cardiopulmonary bypass, the
      effect of thromboxane A2 (vasoconstriction) on the development of organ damage
      may have been influential only during bypass. Both during and after bypass, the
      increase in endothelin excretion (p less than 0.01 to 0.05) was believed to
      induce a further vasoconstriction in the microvasculature. On completion of the
      cardiopulmonary bypass, the elevation of the lysosomal enzyme beta-glucuronidase,
      which is a sensitive indicator of cellular damage, was influenced by the
      concentrations of elastase (r = 0.8) and endothelin (r = 0.52). As evidenced by
      leuko-sequestration in the lung after cardiopulmonary bypass, the increase in the
      alveolar-arterial oxygen tension difference correlated with the elastase
      concentration (r = 0.68). Renal damage, which was detected by an increase in
      renal tubular enzymes (N-acetyl-beta-D-glucosaminidase and gamma
      glutamyltranspeptidase) was affected by the endothelin (r = 0.68, 0.56) and
      elastase levels (r = 0.58, 0.68), respectively, but not by the ratio of
      thromboxane B2 to prostaglandin F1 alpha. The elastase level influenced the
      pulmonary vascular resistance (r = 0.56). However, neither the cardiac index nor
      the systemic and pulmonary vascular resistances were influenced by the endothelin
      level and the ratio of thromboxane B2 to prostaglandin F1 alpha.

PMID- 1355151
TI  - Endothelial cell lining of bioprosthetic heart valve materials.
AB  - To investigate the conditions for endothelial cell lining of glutaraldehyde
      treated bioprosthetic heart valves, we examined in vitro the growth properties of
      endothelial cells on clinically used pericardial valve material and on
      glutaraldehyde-fixed pericardium treated with L-glutamic acid. To improve
      endothelial cell attachment to the valvular surface, we precoated both materials
      either with fibronectin or with fibrillar collagen (95% type I, 5% type III).
      Toxicity of glutaraldehyde, released from clinically used valve material, caused
      endothelial cell death, independent of the type of precoating. Treatment of the
      valve material with L-glutamic acid resulted in regular endothelial cell
      proliferation. We found that collagenous precoating, compared with fibronectin
      precoating, markedly enhanced endothelial cell proliferation and attachment (p
      less than 0.05). Maintenance of antithrombogenic potency of the seeded cells on L
      glutamic acid-treated valve material was proved by regular release of
      prostacyclin. We conclude that bioprosthetic heart valve materials can be lined
      with endothelial cells if toxic glutaraldehyde released from the bioprostheses is
      eliminated.

PMID- 1355152
TI  - Patent foramen ovale in patients with haemodynamically significant pulmonary
      embolism.
AB  - The prevalence of a patent foramen ovale is about 1 in 4. In cases with venous
      thromboembolism and raised right heart pressures, a patent foramen ovale may
      permit paradoxical emboli, which could complicate the course of patients with
      pulmonary embolism. Echocardiography enables detection of a patent foramen ovale
      in life. We have studied 85 patients who presented with haemodynamically
      significant pulmonary embolism as judged by clinical, echocardiographic, or
      haemodynamic indices and who had an echocardiographic evaluation for patent
      foramen ovale. 33 patients (39%) had a patent foramen ovale. Clinical symptoms
      suggestive of paradoxical embolism were more likely in patients with than in
      those without a patent foramen ovale (39% vs 6%, p = 0.00034), with new
      neurological deficits occurring in 11 patients (9 vs 2, p = 0.005) and a vascular
      occlusion in 8 (7 vs 1, p = 0.0096). Arterial oxygen tension was lower in
      patients with a patent foramen ovale (mean 55 [SD 14] vs 62 [16] mm Hg, p =
      0.038). Mortality was not different between the two groups (27% vs 19%).
      Cardiopulmonary complications in terms of resuscitation, intubation, or the use
      of catecholamines were more frequently observed in patients with a patent foramen
      ovale (48% vs 23%, p = 0.028). Patients with a patent foramen ovale and
      haemodynamically significant pulmonary embolism are more likely to have arterial
      hypoxaemia and vascular occlusions, possibly due to paradoxical emboli.

PMID- 1355153
TI  - Bone marrow transplantation for high-risk childhood lymphoblastic leukaemia in
      first remission: experience in MRC UKALL X.
AB  - Bone marrow transplantation (BMT) has been recommended for children with high
      risk acute lymphoblastic leukaemia (ALL) in first remission. The recent MRC UKALL
      X trial was designed to facilitate a non-randomised comparison between BMT and
      chemotherapy in children deemed to be at high risk of treatment failure. 198
      children aged 1-15 had a presenting leucocyte count of more than 100 x 10(9)/l.
      All received induction and early intensification therapy. Children with an HLA
      compatible sibling donor were eligible for BMT in first remission. All other
      children received cranial irradiation at 24Gy, late intensification, and two
      years of continuous treatment. 183 children achieved a stable remission of whom
      111 were HLA typed; these tended to be older and to have T-cell ALL. A donor was
      identified in 41 cases, of whom 34 proceeded to BMT at a median time of 17 weeks;
      there was no difference in distribution of age, sex, or leucocyte count between
      the groups receiving BMT and chemotherapy. Comparison of the 144 children who
      were in remission at 17 weeks and received chemotherapy with the 34 proceeding to
      BMT showed no significant difference in event-free survival at five years (69%
      for BMT and 52% for chemotherapy). There were significantly more treatment
      related deaths in the marrow transplant group (6 vs 4) and more relapses in the
      chemotherapy group (59 vs 4). There was no significant difference in event-free
      survival between children who were HLA typed and had a donor and those without a
      donor, although there were fewer relapses among the former. BMT can be evaluated
      in the context of a multicentre trial for paediatric ALL but the number of
      children with donors is too small to make a significant impact on overall
      survival. However, marrow transplantation was associated with a much lower
      relapse rate than that with the UK ALL protocol, and with better definition of
      higher risk patients BMT may be of benefit in some children with high-risk ALL in
      first remission.

PMID- 1355154
TI  - Antibodies to the human 60 kDa heat-shock protein in patients with schizophrenia.
AB  - Immune mechanisms are thought to be important in a subpopulation of patients with
      schizophrenia. We examined the specificity of neural antibodies in patients with
      schizophrenia to identify a possible antigen. Serum antibodies from patients with
      schizophrenia and control subjects were tested for binding to protein extracts of
      human neuroblastoma cells by western blot. Protein antigens were characterised by
      aminoterminal and internal aminoacid sequence analysis. 14 of 32 (44%) otherwise
      healthy patients with schizophrenia had antibodies to a neuroblastoma protein of
      molecular weight 60 kDa. By partial sequence analysis, this protein was
      identified as the 60 kDa human heat-shock protein (hsp) that is the P1
      mitochondrial protein, and which is 50% homologous to the mycobacterial 65 kDa
      hsp. Antigens that crossreact with hsp65 have been implicated in the pathogenesis
      of adjuvant-induced arthritis in rats and autoimmune diabetes in mice. Of 100
      normal subjects or disease controls, antibodies to hsp60 were found in only 8
      patients, all of whom had active infectious or inflammatory disease. Our results
      support the presence of abnormal immune reactivity involving hsp60 in a subset of
      patients with schizophrenia. The immune response may be related to the
      pathogenesis of the disease.

PMID- 1355155
TI  - Deletions within chromosome 22q11 in familial congenital heart disease.
AB  - Because a locus on chromosome 22q11 is deleted in most individuals with DiGeorge
      and Shprintzen syndromes--conditions in which heart abnormalities are an
      important feature--we have looked for deletions in nine families with recurrent
      outflow-tract heart defects. In five families, chromosome 22 deletions were
      detected in all the living affected individuals studied and also in the
      clinically normal father of three affected children. The deletion was transmitted
      from parents to offspring and was associated with an increase in the severity of
      cardiac defects. No deletions were found in four families in which the parents
      were normal and affected siblings had anatomically identical defects. We propose
      that deletions within band q11 of chromosome 22 are an important cause of
      familial heart defects.

PMID- 1355156
TI  - Splenic lymphoma with villous lymphocytes in tropical West Africa.
AB  - Splenic lymphoma with villous lymphocytes (SLVL) is a monoclonal B
      lymphoproliferative disorder characterised by splenomegaly and distinctive
      villous lymphocytes in the peripheral blood. It has not previously been reported
      from Africa, but we describe ten Ghanaian patients with SLVL seen at one hospital
      during a 4-year period. The clinical presentation is similar in Africa and in
      temperate regions, though the lymphocyte count is higher in African patients and
      the disorder predominantly affects middle-aged women rather than elderly men. It
      is likely that SLVL has previously been classified as splenic chronic lymphocytic
      leukaemia or hyper-reactive malarial splenomegaly.

PMID- 1355157
TI  - Slaked lime and betel nut cancer in Papua New Guinea.
AB  - Oral squamous cell cancer is the most common malignant tumour in Papua New
      Guinea. We have found that oral cancer in this region is concentrated at the
      corner of the mouth and cheek, by striking contrast with western populations, and
      corresponds precisely with the site of application of lime in 77% of 169 cases.
      Powdered slaked lime applied to the chewed Areca nut with Piper betle
      inflorescence at the corner of the mouth causes the mean pH to rise to 10, at
      which reactive oxygen species are generated from betel quid ingredients in vitro.
      Reactive oxygen species, together with sustained lime-induced cell proliferation,
      suggest a possible mechanism of carcinogenesis for this tumour.

PMID- 1355158
TI  - Hirudins: return of the leech?

PMID- 1355159
TI  - Postoperative hypoxaemia.

PMID- 1355160
TI  - Chronic cardiac failure: from centre to periphery.

PMID- 1355162
TI  - Elephantine contraception.

PMID- 1355161
TI  - Serum progesterone in the diagnosis of ectopic pregnancy.

PMID- 1355163
TI  - Risk of human immunodeficiency virus type 1 transmission through breastfeeding.
AB  - Detection of human immunodeficiency virus type 1 (HIV-1) in breast milk by
      culture and polymerase chain reaction does not necessarily mean that
      breastfeeding is a route of transmission, although evidence from several case
      reports points in that direction. We undertook a systematic review of published
      studies meeting criteria that allowed determination of quantitative risk of
      transmission via breastfeeding. Based on four studies in which mothers acquired
      HIV-1 postnatally, the estimated risk of transmission is 29% (95% Cl 16-42%).
      Analysis of five studies showed that when the mother was infected prenatally, the
      additional risk of transmission through breastfeeding, over and above
      transmission in utero or during delivery, is 14% (95% Cl 7-22%). Where there are
      safe alternatives to breastfeeding, universal named testing of pregnant women
      would provide an opportunity to advise more infected women not to breastfeed and
      might thereby reduce the number of vertically infected children. Since
      breastfeeding protects against infant deaths from infectious diseases,
      breastfeeding is still recommended where infectious diseases are a common cause
      of death in childhood, despite the additional risk of HIV transmission.

PMID- 1355164
TI  - Cyclical parenteral nutrition.

PMID- 1355165
TI  - Rapid disappearance of Haemophilus influenzae type b meningitis after routine
      childhood immunisation with conjugate vaccines.
AB  - Mortality from meningitis caused by Haemophilus influenzae type b (Hib), a
      disease that affects mainly infants and young children, can reach 5% in
      industrialised countries and ten times that in non-industrialised countries. To
      determine the efficacy of vaccination against Hib, we carried out a retrospective
      survey of the incidence of Hib meningitis over five decades in the Greater
      Helsinki area of Finland, where all children with bacterial meningitis are
      treated in one of three centres. Except for a meningococcal epidemic in the early
      1970s, Hib was the leading cause of childhood bacterial meningitis until the Hib
      conjugate vaccines changed the picture profoundly. In 1986-87 the polysaccharide
      diphtheria toxoid conjugate (PRP-D) was given experimentally to 50% of infants.
      In 1988-89 all infants were vaccinated, 50% with PRP-D, 50% with another
      conjugate vaccine, the oligosaccharide-CRM197 protein conjugate (HbOC). Since
      1990 a third conjugate vaccine, the polysaccharide-tetanus toxoid (PRP-T), has
      been administered routinely to all infants. The vaccines were administered at age
      3-6 months, with a booster dose at 14-18 months. In the first 5 years of the Hib
      vaccination programme the number of cases of Hib meningitis in children aged 0-4
      years fell sharply, from 30 in 1986 (the first year of the programme) to none in
      1991. The decline contrasts sharply with the rising trend up to the mid 1980s.
      Vaccination seems to be the only explanation for the observed change in the
      epidemiology of Hib meningitis.

PMID- 1355166
TI  - The mouse and the elephant: can primary care save the US health system?

PMID- 1355167
TI  - USA: ban on 415 ineffective drug ingredients.

PMID- 1355168
TI  - Selective decontamination of the digestive tract in intensive care.

PMID- 1355169
TI  - Selective decontamination of the digestive tract in intensive care.

PMID- 1355170
TI  - Selective decontamination of the digestive tract in intensive care.

PMID- 1355171
TI  - Selective decontamination of the digestive tract in intensive care.

PMID- 1355172
TI  - Effect of inhaled corticosteroids on EBV-specific cytotoxic T cells and EBV
      oropharyngeal excretion.

PMID- 1355174
TI  - Insulin resistance and cigarette smoking.

PMID- 1355173
TI  - In-utero fetal therapy with immunoglobulin for alloimmune thrombocytopenia.

PMID- 1355175
TI  - Non-paternity and genetic counselling.

PMID- 1355176
TI  - Idiopathic CD4+ T-lymphocytopenia.

PMID- 1355177
TI  - Idiopathic CD4+ T-lymphocytopenia.

PMID- 1355178
TI  - Idiopathic CD4+ T-lymphocytopenia.

PMID- 1355179
TI  - Idiopathic CD4+ T-lymphocytopenia.

PMID- 1355180
TI  - Hair loss with minoxidil withdrawal.

PMID- 1355181
TI  - Intrapartum fetal monitoring.

PMID- 1355182
TI  - Mechanisms for essential tremor.

PMID- 1355183
TI  - Chemoresistance of Plasmodium falciparum in central Africa.

PMID- 1355185
TI  - Background to the 1992 NEHAWU strike in South Africa.

PMID- 1355184
TI  - Impact of BCG on tuberculous meningitis in France in 1990.

PMID- 1355186
TI  - Euthanasia.

PMID- 1355187
TI  - Monitoring of growth.

PMID- 1355188
TI  - Euthanasia.

PMID- 1355189
TI  - AIDS in Poland.

PMID- 1355191
TI  - Disparities in fees.

PMID- 1355190
TI  - Indian medical journals.

PMID- 1355192
TI  - N-terminal aminoacid sequence of principal allergen of storage mite Lepidoglyphus
      destructor.

PMID- 1355194
TI  - Creutzfeldt-Jakob disease after non-commercial dura mater graft.

PMID- 1355193
TI  - Creutzfeldt-Jakob disease after non-commercial dura mater graft.

PMID- 1355195
TI  - Adverse effects of nonoxynol-9.

PMID- 1355196
TI  - Heart valve stenosis and von Willebrand's factor multimers.

PMID- 1355197
TI  - Vibration and induction of endothelial injury.

PMID- 1355198
TI  - Hepatitis A vaccination.

PMID- 1355199
TI  - Microchimerism of the thymus and graft acceptance.

PMID- 1355200
TI  - Multiorgan failure and disseminated intravascular coagulation in severe
      convulsive seizures.

PMID- 1355201
TI  - Treatment of febrile neutropenic patients receiving antibacterial prophylaxis.

PMID- 1355202
TI  - Continuous versus intermittent infusion of high-dose metoclopramide in prevention
      of cisplatin-induced emesis.

PMID- 1355203
TI  - Doppler sonography and renal graft vessel thromboses after OKT3 treatment.

PMID- 1355204
TI  - Folic acid supplementation and neural tube defects.

PMID- 1355205
TI  - Semi-quantitative detection of Down's syndrome with PCR.

PMID- 1355206
TI  - Molecular analysis of nosocomial infection by oxacillin-resistant Staphylococcus
      aureus lacking protein A and clumping factor.

PMID- 1355207
TI  - Magnesium for hyperventilation in Rett's syndrome.

PMID- 1355208
TI  - Vascular natriuretic peptide.

PMID- 1355210
TI  - Molecular analysis of APC mutations in familial adenomatous polyposis and
      sporadic colon carcinomas.
AB  - Mutations in the APC gene give rise to familial adenomatous polyposis (FAP) and
      also occur in many, perhaps most, sporadic colon cancers. By screening with
      single-strand conformation polymorphism analysis we identified several mutations
      in a small region of the APC gene in both FAP and sporadic cancers. These
      mutations were either point mutations or small deletions or insertions causing
      frameshifts, and all generated stop codons. One 5 base-pair deletion was found in
      a sporadic colon tumour, a colorectal cancer cell line derived from a sporadic
      colon tumour, and in four unrelated FAP patients. This mutation produces
      distinctive heteroduplex bands, which can be detected with a simple non
      radioactive assay. Our findings suggest that highly localised short sequences,
      essentially runs that code for adenine and thymine, may account for up to 20% of
      all observed APC mutations.

PMID- 1355209
TI  - Energy supplementation during pregnancy and postnatal growth.
AB  - The effect of improving maternal nutrition during pregnancy on growth of the
      child has not been assessed, since previous studies supplemented the diets of
      children as well as mothers. In a controlled randomised trial in Madura, East
      Java, pregnant women received a high (HE) or low (LE) energy supplement that
      provided 1950 kJ (465 kcal) or 218 kJ (52 kcal), respectively, in the last
      trimester of pregnancy. The effect of this intervention on the children's growth
      was assessed longitudinally for the first 5 years of life. Only the children of
      mothers who had complied for at least 90 days were included. Infants entered the
      study at birth and their growth was measured at 4-week intervals until 12 months
      old; thereafter they were measured every 3 months. Growth curves were calculated
      from a mathematical model, based on the best fit of actual measurements and the
      age-related growth velocity. Up to the age of 24 months, HE children were
      significantly heavier than LE children (p less than 0.05). HE children were also
      taller throughout the first 5 years (p less than 0.005 from 15 to 48 months, p
      less than 0.05 at both 3-12 and 60 months). Weight-for-height by age was similar
      in both groups, but stunting (height-for-age) was less prevalent in HE children.
      In a community characterised by chronic energy deficiency among women of
      reproductive age, energy supplementation of women for the last 90 days of
      pregnancy was effective in the promotion of postnatal growth and reduction in
      malnutrition of preschool children.

PMID- 1355211
TI  - Risk of cardiac events in atypical transient ischaemic attack or minor stroke.
      The Dutch TIA Study Group.
AB  - Proposed guidelines for the diagnosis of transient ischaemic attack (TIA) involve
      interpretation of symptoms, so it can be very difficult to distinguish a TIA from
      other disorders, such as migraine, epilepsy, syncope, or neurosis. Atypical
      cerebral and visual events may be classified as TIA. To see whether TIA or stroke
      patients with atypical cerebral or visual symptoms are at high or low risk of
      cardiac complications, we prospectively followed 572 patients (entered into the
      Dutch multicentre TIA trial) with a diagnosis of TIA or minor ischaemic stroke,
      but whose symptoms did not fully accord with internationally accepted criteria.
      We compared their outcome with that of 2555 other TIA or stroke patients in the
      trial, who had unequivocal symptoms; all patients were treated with aspirin.
      During mean follow-up of 2.6 years the risk of a major vascular event did not
      differ between the groups (14.5% in patients with atypical symptoms vs 15.1% of
      patients with typical attacks). Patients with atypical attacks had a lower risk
      of stroke (5.6% vs 9.4%, hazard ratio 0.6, 95% confidence interval 0.4-0.9) and a
      higher risk of a major cardiac event (8.4% vs 5.9%, 1.4, 1.0-2.0) than did
      patients with typical attacks. These differences could not be explained by
      differences in cardiac risk factors, and were independent of minor discrepancies
      in baseline characteristics between the groups. A heavy or tired feeling in one
      or two limbs was the only atypical symptom associated with cerebral rather than
      cardiac events (ratio cardiac/cerebral events 0.8). For all other atypical
      symptoms cardiac events were about twice as common as cerebral events (range 1.3
      2.5). Our findings suggest that TIA or minor stroke patients with atypical
      symptoms may have symptomatic heart disease, especially cardiac arrhythmia.

PMID- 1355212
TI  - Efficacy of atovaquone in treatment of toxoplasmosis in patients with AIDS. The
      NIAID-Clinical Center Intramural AIDS Program.
AB  - Atovaquone (formerly 566C80) is a hydroxynaphthoquinone with potent activity
      against Toxoplasma in vitro and in laboratory animals. Eight patients with AIDS
      and presumed or biopsy confirmed toxoplasmosis who were intolerant of or had not
      responded to standard therapies were treated with oral atovaquone 750 mg four
      times a day. Seven patients showed radiographic improvement; the other remained
      radiographically stable. Six patients died 6-60 weeks after enrollment with no
      clinical (six) or necropsy (three) evidence of recurrent toxoplasmosis; two
      patients relapsed at 10 and 32 weeks. Toxicity was mild: only one patient
      required temporary discontinuation of drug due to a rash. Atovaquone is a well
      tolerated drug that appears to be an effective alternative for patients with
      toxoplasmosis who are intolerant of standard therapies.

PMID- 1355213
TI  - Controversy about chickenpox.

PMID- 1355214
TI  - Needlesticks: preaching to the seroconverted?

PMID- 1355215
TI  - Ocular complications of leprosy.

PMID- 1355216
TI  - Non-surgical treatment of stress incontinence.

PMID- 1355217
TI  - Preventable senility: a call for action against the vascular dementias.

PMID- 1355218
TI  - Antifungal chemotherapy in patients with acquired immunodeficiency syndrome.
      British Society for Antimicrobial Chemotherapy Working Party.

PMID- 1355219
TI  - Efficacy and toxicity of eflornithine for treatment of Trypanosoma brucei
      gambiense sleeping sickness.
AB  - The usual first-line treatment for Trypanosoma brucei gambiense sleeping sickness
      is melarsoprol, but when that fails the outlook has hitherto been grim. The
      polyamine synthesis inhibitor eflornithine (difluoromethylornithine, DFMO) has
      emerged as an alternative therapy. 207 patients with late-stage T b gambiense
      sleeping sickness were treated in rural Zaire with three different regimens of
      DFMO in an open-trial design. During treatment, trypanosomes disappeared from the
      CSF of all 87 patients in whom parasites had been seen before DFMO
      administration, and there was a sharp fall in CSF white cell count from a mean of
      186/microliters to 21/microliters. 152 patients have been followed for at least a
      year after DFMO treatment, and only 13 (9%) have relapsed. Treatment failures
      were more common in children less than 12 years, among patients treated with oral
      DFMO only, and among patients who received DFMO as the initial treatment of their
      recently diagnosed trypanosomiasis. Toxicity was acceptable. Only 4 patients died
      during or shortly after treatment. Bone marrow suppression resulting in anaemia
      (43%) or leucopenia (53%) was common but bore little consequence. This open trial
      shows that DFMO is as active as and possibly less toxic than melarsoprol. For
      economic and logistic reasons DFMO may not be the first-choice therapy in rural
      Africa but for the vast majority of patients who relapse after melarsoprol DFMO
      will be curative.

PMID- 1355220
TI  - Are diabetic pre-pregnancy clinics worth while?

PMID- 1355221
TI  - Tobacco-associated deaths.

PMID- 1355222
TI  - Tobacco-associated deaths.

PMID- 1355223
TI  - Limb abnormalities and chorionic villus sampling.

PMID- 1355224
TI  - Aluminum and dementia.

PMID- 1355225
TI  - Cerebrovascular complications after primary varicella-zoster infection.

PMID- 1355226
TI  - Increased myocardial cAMP in patients with transplant coronary vasculopathy.

PMID- 1355227
TI  - Treatment of chronic heart failure.

PMID- 1355228
TI  - Coenzyme Q10, iron, and vitamin B6 in genetically-confirmed Alzheimer's disease.

PMID- 1355229
TI  - Age-related increase of Helicobacter pylori frequency in symptom-free and in
      dyspeptic children.

PMID- 1355230
TI  - Clozapine and hyponatraemia.

PMID- 1355231
TI  - Subacute myopathy during omeprazole therapy.

PMID- 1355232
TI  - Secondary leukaemias after epipodophyllotoxins.

PMID- 1355234
TI  - Fatal hepatitis after herbal tea.

PMID- 1355233
TI  - Toxicity of Chinese herbal remedies.

PMID- 1355236
TI  - Respiratory arrest after N-acetylcysteine for paracetamol overdose.

PMID- 1355235
TI  - Toxicity of Chinese herbal remedies.

PMID- 1355237
TI  - Stapled anastomoses and colon cancer recurrence.

PMID- 1355238
TI  - Transmission of hepatitis C with pasteurised factor VIII.

PMID- 1355239
TI  - A "European Institute of Health".

PMID- 1355240
TI  - Health care and food aid for Somalia.

PMID- 1355241
TI  - Abortion in India.

PMID- 1355242
TI  - Blood donation.

PMID- 1355243
TI  - Selection for audit.

PMID- 1355244
TI  - Distribution of scientific information in Spanish.

PMID- 1355245
TI  - Diet and cancer.

PMID- 1355246
TI  - HIV transmission and the law.

PMID- 1355247
TI  - High versus low dose cisplatin in epithelial ovarian cancer.

PMID- 1355248
TI  - Adjuvant propofol for refractory cisplatin-associated nausea and vomiting.

PMID- 1355249
TI  - Cystic fibrosis mouse with intestinal obstruction.

PMID- 1355250
TI  - Pneumococcal vaccination for travel to Spain.

PMID- 1355251
TI  - Seroprevalence of hepatitis E in The Netherlands.

PMID- 1355252
TI  - Isolation of atypical HIV-1-related retrovirus from AIDS patient.

PMID- 1355253
TI  - Transmission of HIV-associated tuberculosis to health-care workers.

PMID- 1355254
TI  - The electrophysiological actions of dopamine and dopaminergic drugs on neurons of
      the substantia nigra pars compacta and ventral tegmental area.
AB  - The dopaminergic neurons of the substantia nigra pars compacta and ventral
      tegmental area play a crucial role in regulating movement and cognition
      respectively. Several lines of evidence suggest that a degeneration of
      dopaminergic cells in the substantia nigra produces the symptoms of Parkinson's
      disease. On the other hand, a hyperactivity of the dopaminergic transmission in
      the brain induces dyskinesia, dystonia and psychosis. It is also well established
      that the euphoric and rewarding responses evoked by drugs of addiction, such as
      amphetamine and cocaine, are mediated by central dopamine systems.
      Electrophysiological experiments which study the activity of single dopaminergic
      neurons in the ventral mesencephalon have shown that dopamine and dopaminergic
      drugs reduce the firing frequency of these cells. This is due to the stimulation
      of D2-D3 autoreceptors and to a hyperpolarization of the membrane produced by an
      increase in potassium conductance. In addition, substances which increase the
      release (amphetamine), the synthesis (levodopa) or block the uptake (cocaine,
      nomifensine, amineptine) of dopamine in the brain inhibit the firing activity of
      the dopaminergic cells throughout dopamine-mediated mechanisms. In this review,
      we will briefly examine the literature concerning the physiological and
      behavioural responses caused by dopamine and dopaminergic agents on the
      dopaminergic neurons of the ventral mesencephalon. Our conclusion suggests that
      the electrophysiological actions of dopamine and dopamine-related drugs on
      dopaminergic cells in the ventral mesencephalon might be indicative of the
      pharmacological effects of these agents on the brain.

PMID- 1355255
TI  - Stimulatory effects of quinpirole hydrochloride, D2-dopamine receptor agonist, at
      low concentrations on prolactin release in female rats in vitro.
AB  - Dopamine (DA) has dual actions (inhibitory and stimulatory) in the regulation of
      prolactin (PRL) release, depending on its concentration. To investigate the
      stimulatory effects of DA, perifused rat anterior pituitary cells were exposed to
      the highly-specific DA D2 receptor agonist, quinpirole hydrochloride (LY). Very
      low concentrations of LY (10(-12)-10(-10) M) stimulated PRL release and
      potentiated thyrotropin-releasing hormone (TRH)-induced PRL release. Higher
      concentrations of LY did not stimulate. Pretreatment with pertussis toxin (30
      ng/ml, 24 h) completely abolished these effects of LY. The D2 receptor
      antagonist, metoclopramide, also blocked the potentiation by LY of TRH-induced
      PRL release. These data indicate that very low concentrations of dopamine
      stimulate PRL release via an interaction with a D2 receptor connected to a
      pertussis toxin-sensitive G protein.

PMID- 1355256
TI  - Amyl nitrite related deaths.
AB  - Two cases of death associated with amyl nitrite are discussed. An attempt is made
      to highlight its noxious properties and the difficulty in attributing death to it
      when inhaled.

PMID- 1355257
TI  - Possible cell-free prion replication.
AB  - Spongiform encephalopathies, such as scrapie or bovine spongiform encephalopathy
      in animals, or kuru, Creutzfeld-Jakob disease (CJD) and Gerstmann-Straussler
      Scheinker disease (GSS) in man, seem to be caused by a transmissible agent whose
      nature is still a matter of debate. The properties of this agent which has been
      designated as prion, differ from those of any other known infectious agents,
      including viruses and viroids. Several lines of evidence suggest that the prion
      is devoid of nucleic acid and is identical with a modified form of a normal host
      protein. This lack of nucleic acid poses the question of how a protein moiety can
      propagate itself as a transmissible agent. Here it is proposed that prion
      replication is a process similar to crystallization and as such, the propagation
      of prions can take place as a sort of chain-reaction in an in vitro cell-free
      system.

PMID- 1355258
TI  - [Expression of soluble c-erbB-2 protein in serum of gastric cancer patients:
      preliminary report].

PMID- 1355259
TI  - N-methyl-D-aspartate exposure blocks glutamate toxicity in cultured cerebellar
      granule cells.
AB  - Exposure of cultured cerebellar granule cells to glutamate results in a
      concentration-dependent (EC50 = 22.7 +/- 0.4 microM) and delayed (24-72 hr)
      neurotoxicity, which is blocked by the specific N-methyl-D-aspartate (NMDA)
      receptor antagonists 2-amino-5-phosphovalerate and MK-801 but is unaffected by
      the non-NMDA receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and 6,7
      dinitroquinoxaline-2,3-dione. Although glutamate toxicity in these cells is
      mediated by the NMDA subtype of glutamate receptor, pretreatment of cerebellar
      granule cells with subtoxic concentrations of NMDA markedly antagonizes the
      neurotoxic actions of glutamate, with an IC50 of 55 +/- 4 microM. The
      neuroprotective effect of NMDA requires a preincubation time of approximately 120
      min to be fully manifested and does not require the presence of NMDA during
      glutamate exposure. These data demonstrate that NMDA receptors mediate both
      neurotoxicity and neuroprotection in cerebellar granule cells. Among four
      glutamate receptor agonists tested (NMDA, quisqualate, ibotenate, and kainate),
      only NMDA was able to provide a robust neuroprotection against glutamate
      toxicity. Quisqualate was neither neurotoxic nor neuroprotective, whereas
      ibotenate, which was nontoxic by itself, induced a small degree of
      neuroprotection. In contrast, kainate, which was neurotoxic to cerebellar granule
      cells, also provided considerable neuroprotection against glutamate toxicity.
      Because preincubation of cerebellar granule cells with NMDA fails to alter NMDA
      receptor-mediated phosphoinositide hydrolysis or the specific binding of [3H]MK
      801 to NMDA receptors, it appears that the neuroprotective effects of NMDA are
      not due to NMDA receptor desensitization.

PMID- 1355260
TI  - A naturally occurring tyrosine to histidine replacement at residue 33 of human
      thymidylate synthase confers resistance to 5-fluoro-2'-deoxyuridine in mammalian
      and bacterial cells.
AB  - Structural changes in the macromolecular targets of pharmacological agents can
      result in alterations in the efficacy of these agents. In previous studies, we
      identified a variant structural form of thymidylate synthase (TS) that is
      associated with relative resistance to 5-fluoro-2'-deoxyuridine, in a human
      colonic tumor cell line. We now report on the use of DNA transfer techniques to
      examine directly the effects of each TS form on drug response. TS cDNA
      constructs, corresponding to the normal or variant TS mRNA, were expressed in
      Chinese hamster lung cells or in Escherichia coli, and response to 5-fluoro-2'
      deoxyuridine was determined. We observed that expression of the variant TS, which
      differs from the normal form by a tyrosine to histidine substitution at residue
      33, confers a 4-fold level of drug resistance in the mammalian cells, as well as
      in bacteria. The possible role of Tyr-33 in 5-fluoropyrimidine-mediated
      inhibition of TS is discussed.

PMID- 1355261
TI  - Characterization of functional interactions of imidazoquinoxaline derivatives
      with benzodiazepine-gamma-aminobutyric acidA receptors.
AB  - U-78875 [imidazo[1,5-a]quinoxalin-4(5H)-one, 3-(5-cyclopropyl-1,2,4-oxadiazol-3
      yl)-5-(1-methylethyl)] belongs to a series of imidazoquinoxaline derivatives,
      recently discovered ligands with high affinity for benzodiazepine receptors. In
      this study, we have examined the drug and its analogs for their modes of
      interaction with the receptors, with a particular emphasis on finding molecular
      determinants for their functional properties. Changes in the substituents on N5
      and C6 of the heterocyclic ring produced no major effects on binding
      characteristics but yielded drugs of widely varying efficacy (antagonist to full
      agonist), measured as gamma-aminobutyric acid (GABA)-mediated 36Cl- uptake and t
      butylbicyclophosphoro[35S]thionate binding in rat cerebrocortical membranes. The
      relative binding affinity and efficacy of the analogs measured in brain membranes
      were similar to those in cloned GABAA receptors of the alpha 1 beta 2 gamma 2
      (type I) and alpha 3 beta 2 gamma 2 (type II) subtypes. The imidazoquinoxalines
      showed no marked subtype selectivity. Their Ki value against [3H]flunitrazepam
      binding for type I was only 2-3 times lower than that for type II, and their rank
      order for agonistic activity was the same in the two subtypes, measured as GABA
      mediated Cl- currents in human kidney cells (A293) expressing the subtypes of
      GABAA receptors. According to computational modeling of the drugs using both
      molecular and quantum mechanics, the agonistic activity of the imidazoquinoxaline
      derivatives depends on the presence of a bulky alkyl substituent at N5 and the
      deformation of the substituted portion of the otherwise planar ring system
      induced by a bulky moiety at N5 or C6. With a fixed N5 substituent (isopropyl),
      the relative efficacy in the brain membranes, as well as in the cloned receptors,
      appeared to be dependent on the degree of the ring deformation. This out-of-plane
      portion of the imidazoquinoxalines can be assigned to the general region occupied
      by the 5-phenyl group of diazepam and other agonistic functional groups of
      several nonbenzodiazepine ligands. It seems that this region, apparently common
      to various agonistic ligands, interacts with an agonistic pocket in type I and
      type II subtypes of the benzodiazepine receptors in the brain. Our results also
      provide direct support for the view that the agonists and nonagonists share
      largely overlapping binding regions in the benzodiazepine receptor, which has
      been proposed earlier from in vivo efficacy measurements of other series of
      ligands.

PMID- 1355263
TI  - Cyclic AMP potentiates receptor-stimulated phosphoinositide hydrolysis in human
      neuroepithelioma cells.
AB  - A stimulatory role for cAMP in the regulation of receptor-activated
      phosphoinositide hydrolysis has been examined in human SK-N-MCIXC and SK-N-MCIIE
      neuroepithelioma cells. The addition of optimal concentrations of oxotremorine-M,
      norepinephrine, endothelin-1, and ATP enhanced the release of inositol phosphates
      by 2-9-fold after activation of muscarinic, alpha 1-adrenergic, endothelin, and
      P2 nucleotide receptors, respectively. All combinations of these agonists
      elicited a release of inositol phosphates that was at least additive. However,
      the combined presence of oxotremorine-M and norepinephrine resulted in a
      phosphoinositide hydrolysis that was 30% greater than additive. This potentiation
      of inositol lipid hydrolysis resulted from an increased activity of the
      muscarinic receptor after the addition or norepinephrine and persisted after
      alpha 1-adrenergic receptor blockade. The enhancement of muscarinic receptor
      stimulated inositol phosphate release could be quantitatively mimicked by
      inclusion of the beta-adrenergic agonist isoproterenol (EC50 approximately 0.1
      microM), but not by alpha 1- or alpha 2-adrenergic agonists. Potentiation of
      oxotremorine-M-stimulated inositol lipid hydrolysis observed in the presence of
      either norepinephrine or isoproterenol was reduced in the absence of added Ca2+.
      Addition of either norepinephrine or isoproterenol to SK-N-MCIXC cells also
      resulted in a 16-fold increase in cAMP concentration. Although the cell-permeant
      8-chloro-4-phenylthio-cAMP had a small inhibitory effect on basal inositol
      phosphate release, its inclusion resulted in a 19-31% enhancement of muscarinic,
      endothelin, ATP, and alpha 1-adrenergic receptor-stimulated phosphoinositide
      hydrolysis. We conclude 1) that, in SK-N-MCIXC cells, the addition of beta
      adrenergic agonists selectively enhances muscarinic receptor-stimulated
      phosphoinositide hydrolysis through a cAMP-dependent process and 2) that the
      ability of exogenously added cAMP to enhance the activation of all four inositol
      lipid-linked receptors indicates that the effects of cAMP on inositol lipid
      hydrolysis are compartmentalized in these cells.

PMID- 1355262
TI  - Molecular pharmacological differences in the interaction of serotonin with 5
      hydroxytryptamine1C and 5-hydroxytryptamine2 receptors.
AB  - 5-Hydroxytryptamine (5HT)1C and 5HT2 receptors appear to be closely related, from
      a molecular viewpoint, displaying similar second messenger systems and a high
      degree of sequence homology. However, there are striking differences in the
      interactions of 5HT with 5HT1C and 5HT2 receptors; 5HT is generally more potent
      in stimulating responses mediated through 5HT1C receptors than responses mediated
      through 5HT2 receptors. Also [3H]5HT labels 5HT1C receptors and not 5HT2
      receptors. In order to explore more fully the molecular rationale for these
      differences, radioligand binding studies were performed in rat, human, and
      porcine brain and choroid plexus tissues and in mammalian cells transfected with
      rat 5HT1C or 5HT2 receptors; second messenger studies (inositol phosphate
      accumulation) were performed in the transfected cells. The second messenger
      studies confirmed the approximately 10-fold higher potency of 5HT in stimulating
      intracellular responses through 5HT1C receptors (EC50 = 8.3 nM) than in
      stimulating intracellular responses through 5HT2 receptors (EC50 = 101 nM). An
      agonist radioligand selective for the 5HT1C and 5HT2 receptors, 2,5-dimethoxy-(4
      [125I]iodo)phenylisopropylamine, was used, as well as [3H]5HT, [3H]mesulergine
      (antagonist radioligand for 5HT1C receptors), and [3H]ketanserin (antagonist
      radioligand for 5HT2 receptors). Computer-assisted analyses of the binding data
      revealed two agonist affinity states for the 5HT1C receptor. The agonist high
      affinity state of the receptor was modifiable by guanyl nucleotides. The
      proportion of agonist high affinity states, relative to the total receptor
      population, was approximately 10% for both receptors. The apparent higher
      affinity of 5HT for the radiolabeled 5HT1C receptors was due to the higher
      affinity 5HT displayed for the agonist low affinity state of the 5HT1C receptor,
      compared with the affinity of 5HT for the agonist low affinity state of the 5HT2
      receptor. The correspondence between the higher affinity of 5HT for the agonist
      low affinity state of the 5HT1C receptor, relative to the 5HT2 receptor, and the
      higher potency of 5HT in stimulating 5HT1C responses indicates that 5HT interacts
      with the agonist low affinity state of the 5HT1C and 5HT2 receptors in initiating
      its biological effects. These observations indicate that guanine nucleotide
      binding protein (G protein)-coupled receptors can exhibit high affinity for
      neurotransmitters in both the free receptor and the G protein-coupled states and
      that receptors exhibiting this property may represent a novel subfamily of G
      protein-coupled receptors.

PMID- 1355264
TI  - Preferential block of T-type calcium channels by neuroleptics in neural crest
      derived rat and human C cell lines.
AB  - We have used the whole-cell version of the patch-clamp technique to analyze the
      inhibition of Ca2+ currents by antipsychotic agents in neural crest-derived rat
      and human thyroid C cell lines. Diphenylbutylpiperidine (DPBP) antipsychotics,
      including penfluridol and fluspirilene, potently and preferentially block T-type
      Ca2+ current in the rat medullary thyroid carcinoma 6-23 (clone 6) cell line.
      When step depolarizations were applied at 0.1 Hz from a holding potential of -80
      mV, with 10 mM Ca2+ as the charge carrier, the DPBP penfluridol inhibited T-type
      current with an IC50 of 224 nM. High voltage-activated L and N currents were less
      potently blocked. At a concentration of 500 nM, penfluridol inhibited 78.0 +/-
      2.3% (n = 29) of inactivating T-type Ca2+ current, whereas the sustained high
      voltage-activated current was reduced by 25.6 +/- 3.5% (n = 28). Block of T-type
      current by penfluridol was enhanced by depolarizing test pulses applied at
      frequencies above 0.03 Hz. The use-dependent component of block was largely
      reversed by pulse-free periods at -80 mV. T-type Ca2+ channels in the human TT C
      cell line were blocked by penfluridol, and the potency was enhanced by reduction
      of extracellular Ca2+. Non-DPBP antipsychotics, including haloperidol, clozapine,
      and thioridazine, also blocked T-type channels, but these were 20-100 times less
      potent than the DPBPs. These results identify the DPBPs as a new class of organic
      Ca2+ channel antagonists, which are distinctive in their ability to
      preferentially block T-type channels. These agents will be useful in defining the
      function of T channels in various excitable cells. Their potent block of T-type
      Ca2+ channels, which would be enhanced in rapidly firing cells, suggests that
      this action may be relevant to the therapeutic or toxic effects of these drugs
      when used in clinical pharmacology.

PMID- 1355265
TI  - Theoretical studies on the histamine H2 receptor: molecular mechanism of action
      of antagonists.
AB  - The previously defined sites in the histamine H2 receptor model [Mol. Pharmacol.
      40:980-987 (1991)] were used to elucidate the pharmacological mechanism of action
      of compounds that act as antagonists at the receptor. In this model, a formate
      anion is used both as the negative site at which the histamine cation is anchored
      to the receptor and as a proton acceptor site. An ammonium cation is used as a
      proton donor site. The proposed model of recognition of cimetidine, tiotidine,
      and ranitidine suggests that the monocationic form of the antagonists is the most
      favorable species to bind the receptor. Moreover, the mode of recognition follows
      the same trends obtained for compounds that act as agonists; the protonated site
      of the molecule, i.e., imidazolium in cimetidine, guanidinium in tiotidine, or
      substituted ammonium in ranitidine, anchors at the negative site of the receptor,
      whereas the nonbasic part, i.e., cyanoguanidine in cimetidine and tiotidine and
      nitrodiaminoethene in ranitidine, is located between the proton donor and
      acceptor sites. An energetic analysis of the interaction between the antagonists
      and the receptor model, including the energies of ligand desolvation, shows that
      histamine cannot compete effectively with cimetidine, tiotidine, or ranitidine
      for binding to the H2 receptor. The predicted order of antagonist potencies,
      based on differences of formation enthalpies (delta delta H1), reproduces
      qualitatively the experimental rank order.

PMID- 1355266
TI  - Typing of human papillomaviruses by polymerase chain reaction amplification with
      L1 consensus primers and RFLP analysis.
AB  - Human papillomaviruses (HPV) cause benign and malignant lesions of the epithelial
      and mucosal surfaces. Certain virus types are associated with cervical
      carcinomas, while others are associated with benign condylomata. We have
      developed a rapid method for determining HPV type that is based on restriction
      fragment length polymorphism (RFLP) analysis within the L1 region of HPVs that is
      amplified by PCR using the consensus primers described by Manos et al. Analysis
      of the product generated by PCR amplification of plasmids containing cloned HPV
      genomes and of 88 clinical specimens, known to contain HPV viral DNA by previous
      hybridization analysis, revealed that this method is useful for typing HPV
      sequences amplified from a variety of sources including cervical lavages, fresh
      tissue, and paraffin-embedded formalin-fixed biopsy material. The method can
      differentiate between most known types of HPV and discriminate between infections
      with single, multiple or novel HPV types. A high correlation (86%) was obtained
      when this method was compared with PCR amplification and Southern blot
      hybridization analysis of PCR product, or Southern blot hybridization analysis of
      total genomic DNA. Differences in typing occurred mostly for specimens that
      contained multiple or new/unknown HPV types. However, RFLP typing easily
      identified repeated patterns for new HPV types that were not detected by the
      other methods. In summary, PCR-RFLP typing is a sensitive and specific method to
      identify and characterize rapidly HPV DNA in clinical specimens from a variety of
      sources.

PMID- 1355267
TI  - Life-threatening ventricular arrhythmias in patients with silent myocardial
      ischemia due to coronary-artery spasm.

PMID- 1355268
TI  - Circulating intercellular adhesion molecule 1 as a marker of disease progression
      in cutaneous melanoma.

PMID- 1355269
TI  - Interactions between valproate, glutamate, aspartate, and GABA with respect to
      uptake in astroglial primary cultures.
AB  - Astrocytes have been proposed to regulate the extracellular space in the brain,
      even if rather little is known about their specific functions. One possibility
      for obtaining more knowledge on the functions of astroglial cells is to examine
      how they respond on exposure to pharmacological agents. Na(+)-valproate is an
      anticonvulsive drug which is used in the treatment of several types of epilepsy.
      The mechanisms of action of the drug are not fully understood, but the GABA-ergic
      system, both in neurons and astrocytes, has been shown to be affected. In the
      present study, the effects of valproate were investigated on astroglial cells in
      primary cultures from newborn rat cerebral cortex. The transport of the drug
      itself and its effects on the transport of the amino acid transmitters glutamate,
      aspartate and gamma-aminobutyric acid (GABA) into astrocytes were examined. The
      [3H]valproate transport into the astrocytes was increased after exposure to L
      glutamate but not L-aspartate. On the other hand, after acute exposure for the
      drug, the transport of [3H]L-glutamate and [3H]L-aspartate decreased, as also did
      the affinity but not the transport capacity for the [3H]GABA uptake. However,
      after 5 days chronic valproate exposure, no effects could be seen on the uptake
      kinetics of L-glutamate or L-aspartate. For GABA, the affinity decreased, while
      the transport capacity remained unchanged compared with controls. The results
      showed that valproate, glutamate, aspartate and GABA were capable of interacting
      significantly with each others transport into the astrocytes.

PMID- 1355271
TI  - Intraoperative neurophysiological monitoring.

PMID- 1355272
TI  - A non-linear haemodynamic model for the arterial pulsatile component of the
      intracranial pulse wave.
AB  - An indication that pressure pulses in cerebral arteries may play a role in the
      configuration of intracranial pressure pulsations is given by the observation
      that vasospasm of cerebral arteries narrows the amplitude of the intracranial
      pressure wave. The present work develops a mathematical model for the
      transmission of arterial pressure pulses across the compliant arterial wall to
      the surrounding intracranial space. Compliance of both the arterial segment and
      the intracranial space are considered. So as to retain accuracy at higher values
      of the mean intracranial pressure, a physiological range in which pulse
      transmission is enhanced due to lower pressure gradients but intracranial
      compliance is not necessarily decreased, a logistic fit is used to model the
      intracranial pressure-volume relationship. A sequence of approximations (with
      error bounds) is obtained for the induced intracranial pressure pulse amplitude
      as a function of arterial pulse amplitude, mean transmural pressure, and mean
      intracranial pressure. It is found that at higher mean intracranial pressures,
      where the usual exponential assumption for the intracranial pressure-volume curve
      loses validity, the amplitude of the transmitted arterial pressure pulse depends
      non-linearly on the mean intracranial pressure.

PMID- 1355273
TI  - Capillary filling analysis by digital subtraction angiography for vertebro
      basilar insufficiency.
AB  - Vertebro-basilar insufficiency (VBI) is a vague clinical entity including several
      symptoms such as faintness, dizziness, vertigo. Millikan and Siekert reported a
      'syndrome of intermittent insufficiency of basilar arterial system'. But vascular
      abnormalities responsible for such symptoms are often hardly diagnosed by
      conventional angiography, because vertebro-basilar artery systems have many kinds
      of anomalous congenital origins. Conventional angiography gives us arterial
      informations such as stenosis, occlusion and malformations, but it often fails to
      reveal capillary perfusions because of its relatively poor density resolution.
      Digital subtraction angiography (DSA) is considered to have improved density
      resolution, and it may enable us to detect vascular perfusions more sensitively
      in the capillary phase. In this study, we evaluated the usefulness of the
      capillary filling analysis in digital subtraction angiography for diagnosis of
      VBI.

PMID- 1355270
TI  - High-affinity transport of choline and amino acid neurotransmitters in
      synaptosomes from brain regions after lesioning the nucleus basalis
      magnocellularis of young and aged rats.
AB  - Bilateral lesion of the nucleus basalis with ibotenic acid infusions in young and
      aged rats results in the degeneration of cholinergic neurons which innervate the
      cortex. As expected, high-affinity uptake of choline was decreased in the frontal
      cortex subsequent to the lesion. Twenty one days after surgery there was a
      significantly decrease of the transport rate of GABA, glutamate and glycine in
      the frontal cortex of young rats, but those activities showed a recovery six
      months after lesion. On the contrary, 12-month old rats lesioned with the same
      experimental protocol showed no recovery of the transport rates in the frontal
      cortex. Uptake of choline, GABA, glutamate and glycine has also been studied in
      other areas of the brain, namely, hippocampus, olfactory bulb and cerebellum. The
      present results suggest that lesioning the nucleus basalis of rats led to a more
      effective and permanent impairment of some biochemical functions of the brain,
      when compared to young lesioned animals, and also suggest a functional
      relationship between the nucleus basalis and other areas of the brain.

PMID- 1355274
TI  - Spontaneous symmetry breaking and the onset of chaos in a muscle model.
AB  - The Hill length-tension curve of a muscle fibre is not linear. This had led us to
      investigate the behaviour of a model muscle sarcomere. The muscle is modelled as
      an oscillator of mass m subject to a nonlinear restoring force, a periodic
      external driving force and friction. We have found that this simple, idealized
      model exhibits spontaneous symmetry breaking and transition to chaos via a period
      doubling sequence. This result suggests that the nonlinearity in the length
      tension curve of a muscle fibre could be responsible for irregular temporal
      behaviour and muscle tremor.

PMID- 1355275
TI  - Reduced latency of the visual evoked cortical response following cryogenic injury
      to the cerebral cortex--a neuroexcitatory phenomenon.
AB  - Changes in the latency of visual cortical evoked responses (VER) were studied in
      rats subjected to cryogenic injury of the cerebral cortex. Four hours after cold
      injury the animals revealed a significant reduction of VER latency, which lasted
      approximately one week, with maximal reduction in latency occurring after 3 days.
      A potential role of excitotoxic amino acids in this phenomenon was tested by
      direct application of glutamate to the exposed cerebral cortex of the control rat
      and by administration of MK-801, antagonist of the NMDA receptor, in rats
      subjected previously to cryogenic injury and displaying a significant reduction
      in the VER latency. The direct application of glutamate to the cortex resulted in
      a decrease of the VER latency similar in magnitude to that observed after cold
      injury and this effect could repeatedly be demonstrated after washing out the
      initial application of the glutamate. The administration of MK-801 in animals
      subjected previously to cryogenic injury produced, within 5 minutes, reversion of
      reduced VER latencies. The maximal prolongation of latency occurred 30 min after
      MK-801 administration and reached in some cases latency values greater than in
      controls. Reduced latencies, corresponding to those observed originally,
      reappeared within 2 to 4 hours. Our studies suggest that the described reductions
      in the VER latencies are related to cortical areas of hyperexcitation due to
      excessive release of neuroexcitatory transmitters.

PMID- 1355276
TI  - Mutations in transmembrane domain of c-erbB-2 gene in human malignant tumours of
      the central nervous system.
AB  - Point mutations in the transmembrane domain of c-erbB-2 gene in human brain
      tumours were studied by DNA amplification with the polymerase chain reaction
      method. Amplified gene fragments in M13 phage vector were cloned, and subsequent
      nucleotide sequences were determined. Studied specimens were 10 human malignant
      and 3 human benign tumours of the central nervous system, and a normal human
      placenta. In malignant tissues, Val-to-Glu mutation that induces transforming
      activity of c-erbB-2 did not appear to codon 659 of c-erbB-2. In malignant
      tissues, many other types of mutations appeared in low frequency, either at codon
      659 or other positions of the transmembrane domain of c-erbB-2. The ratio of
      mutated genes to normal genes was very low in all specimens of malignant tumours.
      The point mutations were not observed in benign brain tumour or normal human
      placental tissues. The transmembrane domain of c-erbB-2 may have several highly
      mutable hot spots, where brain tumour tissues show a predilection for point
      mutation.

PMID- 1355277
TI  - Management of pineal region tumours.
AB  - Pineal region tumours represent a colourful, challenging peculiarity of brain
      pathology. Views on their management are still much divided and controversial.
      Data of fifty patients with the whole palette of these tumours seen in the
      National Institute of Neurosurgery have been analysed in view of the result of
      management versus histology of these tumours. Findings of tumour marker studies
      have not at all been conclusive in predicting histology and outcome, however,
      cytology of the cerebrospinal fluid (CSF), if positive, pointed toward a very
      gloomy management result in all cases. Merits of infratentorial-supracerebellar,
      occipito-transtentorial approaches of direct surgery, palliative interventions
      and their timing, as well as that of irradiation are discussed in comparison with
      opinions and arguments from the literature. Shunt procedures alone proved to be
      dangerous in some cases by evoking haemorrhagic complications. In carefully
      selected cases microsurgical intervention gave the best possible results in
      expansively growing pineal region tumours. There is still place for irradiation
      and chemotherapy, again, in certain types of mass lesions.

PMID- 1355278
TI  - Decreased visual evoked cortical response latency associated with cerebral
      ischaemia in the gerbil.
AB  - The observation of Xu et al. concerning reduction in latency of the visual evoked
      responses (VER) following cortical cryogenic injury, prompted us to ascertain
      whether similar VER changes could be demonstrable after ischaemic brain injury,
      especially, since both conditions have in common involvement of neuroexcitatory
      mechanisms. In our study, the Mongolian gerbils, which were subjected to 10 min
      bilateral carotid occlusion ischaemia, revealed decreased latency of the VER,
      with the peak of latency reduction between 4 and 7 h. An almost immediate
      decrease in VER latency was observed when glutamate was directly applied to the
      pial surface of the brain. These observations indicate that the reduction of VER
      latency may be related to neuroexcitation induced by release of excitatory amino
      acids, the latter constituting a widespread phenomenon, concomitant with brain
      injuries of various aetiologies.

PMID- 1355279
TI  - Infantile acute encephalopathy with combined symmetrical hypodensities in the
      thalami and the putamen on computed tomography.
AB  - An eight-month-old boy with clinical features of acute encephalopathy with
      symmetrical low-density areas in the thalami and the putamen on computed
      tomography is presented. These particular computed tomography features suggest
      potential aetiology common to acute encephalopathy with low-density areas in the
      thalami and infantile bilateral striatal necrosis with an acute onset. The
      therapeutic consideration of these conditions is also discussed.

PMID- 1355280
TI  - Dielectric measurement of cerebral water content using a Network Analyzer.
AB  - At present, no practical method exists for monitoring the progression and
      severity of cerebral oedema in a clinical setting on a continuous basis. In
      search for such a method, we investigated the electrical characteristics of
      cerebral tissue at microwave frequencies to quantify cerebral oedema. The
      dielectric constants of normal and oedematous canine cerebral white matter were
      measured using a Network Analyzer and then compared to the tissue's water
      content. In addition, salt infiltration and time elapsed after excision of the
      tissue were examined to determine their effects on the measurements. The water
      content and dielectric constant of the white matter were linearly related
      (correlation coefficient, r = 0.903), comparable to results obtained with a Time
      Domain Reflectometer in previous research. The Network Analyzer, however, is a
      more robust measurement device and, because of this, can potentially be used for
      long term measurements. Further, it was found that neither an increased tissue
      salt content nor the amount of time after excision of the tissue significantly
      affected the results. This indicates that the dielectric constant of cerebral
      white matter is mainly a function of the tissue's water content.

PMID- 1355281
TI  - Microsurgical anatomy of the lower basilar artery.
AB  - This study was designed to study the microvascular anatomy of the basilar artery
      between the superior cerebellar artery and the vertebrobasilar junction (i.e. the
      lower basilar artery). Twenty unfixed brains were injected with silicone rubber
      solution and studied with a Zeiss OPMI microscope. The length of this segment of
      the basilar artery was 28.1 + 1.35 mm and its course was straight in 9 (45%)
      brains, curved in 7 (35%) and tortuous in 4 (20%). The total number of
      perforators found in 20 brains was 340 with an average of 17 per brain. Of these,
      118 (34.7%) were median and 222 (65.2%) were lateral. Median branches had a mean
      length of 5.8 + 1.25 mm, whereas left and right lateral branches had a mean
      length of 16 + 1.25 mm and 16 + 1.58 mm respectively.

PMID- 1355282
TI  - Characterization of human gliomas by a monoclonal antibody both on tissue culture
      and paraffin-embedded sections.
AB  - A monoclonal antibody designated OITIC3-11 was produced against GFAP positive
      human glioblastoma multiforme tumour cells. The specificity of the monoclonal
      antibody was tested on different types of human brain tumours and on normal adult
      brain both on tissue cultures and paraffin-embedded sections. The OITIC3-11
      monoclonal antibody reacted with 16 of 18 malignant and 1 of 6 benign gliomas but
      did not react with meningioma, pituitary adenoma, metastatic brain tumours and
      normal adult brain tissue.

PMID- 1355283
TI  - Detection and partial purification of ischaemia-related neurotrophic activity in
      the periinfarcted brain tissue.
AB  - In the rat model of middle cerebral artery (MCA) occlusion, axons originating
      from the ipsilateral cortical and thalamic neurons are injured by ischaemia. The
      cortical neurons survive thereafter without retrograde degeneration, but thalamic
      neurons slowly die because of retrograde degeneration. The fate of these two
      neurons is remarkably different and may be related to neurotrophic activity
      induced by ischaemia. We detected ischaemia-related neurotrophic activity, and
      partially purified the factor. Tissue samples were obtained from the cortex
      adjacent to the infarction and contralateral corresponding site at 4, 8 and 12
      days after occlusion of the MCA. They were homogenated with a culture medium and
      ultracentrifuged. The supernatant was obtained and used for neurotrophic assay.
      Foetal cortical neurons were obtained from 17 days rat embryo and cultured.
      Neurotrophic activity was assayed by applying tissue extract to the culture
      medium. Application of periischaemic cortical extract obtained at 8 and 12 days
      after ischaemia improved neuronal survival by 50% and 200% as compared to
      contralateral cortical extract, respectively. The activity was not detectable at
      4 days after ischaemia. The neurotrophic activity disappeared by heating the
      extract at 90 degrees C for 10 min. We fractionated the extract by saturated
      ammonium sulphate precipitation, followed by gel-filtered with Superose 12
      column. The neurotrophic activity was detected in the precipitation of 30 to 60%
      saturation fraction of ammonium sulphate. With gel-filtration we separated
      neurotrophic activity in several fractions, which included marker proteins of 8,
      22 and 30 kilodaltons. The activities were only detected in the lesioned side but
      not in the contralateral side.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355284
TI  - Treatment of vasospasm by balloon angioplasty: experimental studies and clinical
      experiences.
AB  - The vasodilation mode and degree of the invasion caused by balloon angioplasty
      were experimentally examined. Assessment by light microscopy and scanning
      electron microscopy demonstrated that the invasion to the implanted arterial
      wall, taken from a patient who died from vasospasm, was minimized by the use of
      the balloon under the condition at 1 atm, 10 times for 10 seconds. Furthermore,
      we applied angioplasty to eight patients who developed severe vasospasm after
      subarachnoid haemorrhage, and five showed improvement in neurophysiological
      (transcranial Doppler sonography), neuroradiological, and clinical examinations.
      In addition, blood vessels obtained from one patient who died 10 days after
      angioplasty, demonstrated similar findings to those of the experimental studies.
      It can be said that angioplasty will be one of the effective therapeutic methods
      to manage vasospasm when it is applied under the conditions mentioned above.

PMID- 1355285
TI  - Cerebrospinal fluid beta-2-microglobulin in multiple sclerosis and AIDS dementia
      complex.
AB  - Cerebrospinal fluid (CSF) and serum concentrations of beta-2-microglobulin (beta
      2-m) were evaluated in 19 patients with clinically definite multiple sclerosis
      (MS), in 21 with AIDS dementia complex (ADC), and in 20 subjects with other
      neurological diseases (OND). CSF beta-2-m and CSF/serum beta-2-m ratio were
      significantly higher in the patients with ADC than in the MS and OND patients.
      The CSF and serum levels of beta-2-m in MS patients were not significantly
      different from those of OND patients. These findings indicate that CSF beta-2-m
      and CSF/serum ratio may be a useful marker in the diagnosis of ADC. In MS
      patients the beta-2-m CSF determinations are of no value.

PMID- 1355286
TI  - The diagnostic utility of elevation in cerebrospinal fluid beta 2-microglobulin
      in HIV-1 dementia. Multicenter AIDS Cohort Study.
AB  - We measured serum and CSF beta 2-microglobulin (beta 2M) levels in HIV-1
      seropositive individuals with and without dementia to determine the frequency and
      diagnostic utility of elevation of CSF beta 2M. We compared 34 samples from 27
      patients with HIV-1 dementia with 110 samples from 54 HIV-1 seropositive
      participants in the Multicenter AIDS Cohort Study, none of whom had progressive
      dementia. Neurosyphilis and CNS opportunistic processes were excluded in all
      subjects. We stratified the nondemented subjects by duration of HIV
      seropositivity and peripheral blood CD4 count. Compared with the nondemented
      group, demented subjects had significantly higher CSF total protein, IgG%, and
      CSF albumin/serum albumin ratios. A highly significant association was found
      between elevated CSF beta 2M and reduced CD4 count (p less than 0.0001). No
      significant differences were noted between the demented and nondemented groups in
      CSF WBC count or in the frequency of CSF HIV-1 isolation. The mean CSF beta 2M
      was 1.9 mg/l in the nondemented subjects compared with 4.2 mg/l in those with
      dementia (p less than 0.0001). We derived a cutoff of 3.8 mg/l from the
      distribution of CSF beta 2M in the nondemented group. The determination of CSF
      beta 2M had a sensitivity of 44%, specificity of 90%, and a positive predictive
      value of 88% for diagnosis of HIV dementia when compared with nondemented
      subjects with CD4 counts less than 200. In those without dementia, there was a
      strong correlation between serum and CSF beta 2M (r = 0.50, p less than 0.0001),
      but in demented subjects CSF beta 2M was elevated independently of serum levels,
      suggesting that CSF beta 2M is produced within the brain in HIV dementia. In the
      absence of CNS opportunistic processes, elevated CSF beta 2M greater than 3.8
      mg/l is a clinically useful marker for HIV dementia.

PMID- 1355287
TI  - Oliguria, hemoptysis, and arthralgias in an otherwise healthy woman.

PMID- 1355288
TI  - Bilateral localized orbital neurofibromas.
AB  - BACKGROUND: The authors report on a 30-year-old man who presented with
      progressive bilateral exophthalmos over a 2-year period. FINDINGS: Computed
      tomography showed large heterogeneous masses in the superior aspect of both
      orbits. Excisional biopsy via bilateral lateral orbitotomies showed the tumors to
      be well-circumscribed, relatively avascular, localized neurofibromas. The patient
      had several features suggestive of multiple endocrine neoplasia type IIB,
      including Marfanoid habitus, enlarged corneal nerves, thickened lips, and mucosal
      neuromas. CONCLUSION: Localized neurofibromas are rare in the orbit and, unlike
      plexiform neurofibromas, are not typically associated with von Recklinghausen's
      neurofibromatosis. Bilaterality of such localized neurofibromas has not been
      previously reported. Recognition of ophthalmic lesions suggestive of multiple
      endocrine neoplasia IIB should prompt evaluation for systemic manifestations of
      this disorder.

PMID- 1355289
TI  - [Reduction of the infant mortality rate in the regions with feldsher and
      midwifery stations].

PMID- 1355290
TI  - 15th European conference on Visual Perception. Pisa, Italy, 30 August-3
      September, 1992. Abstracts.

PMID- 1355291
TI  - Pushed to the margin?

PMID- 1355293
TI  - Immunocytochemical and ultrastructural abnormalities of islet tissue in patients
      with VIP-producing tumors of the pancreas.
AB  - Nontumoral endocrine pancreas from three patients with malignant vasoactive
      intestinal polypeptide (VIP)-omas and the Verner-Morrison (watery diarrhea,
      hypokalemia, and hypoachlorhydria) syndrome was studied immunocytochemically,
      ultrastructurally, and morphometrically. Compared with normal islets from control
      subjects, those of the VIPoma-associated pancreas showed a decrease of
      immunoreactive insulin in B-cells associated with cytological features indicative
      of enhanced insulin synthesis and secretion and an increase in the number of
      immunoreactive somatostatin- and pancreatic polypeptide-containing cells, in the
      absence of ultrastructural signs of modified secretory activity. No substantial
      alterations of A-cells were observed. In addition, images of diffuse de novo
      formation of ducts and islet tissue were often found. Possible mechanisms
      involved in determining the above changes are discussed.

PMID- 1355292
TI  - Prenatal diagnosis of autosomal dominant polycystic kidney disease using flanking
      DNA markers and the polymerase chain reaction.
AB  - A prenatal diagnosis was carried out on a 9-week-old fetus at risk for autosomal
      dominant polycystic kidney disease (ADPKD). Ten members of the family were
      previously typed using five DNA markers linked to the PKD1 locus on chromosome
      16, and one marker linked to the putative PKD2 locus on chromosome 2. The
      polymerase chain reaction (PCR) was used to amplify the D16S125 locus. Pairwise
      and multipoint lod scores indicated that the family was most likely segregating a
      PKD1 mutation. The fetus inherited the disease haplotype from the affected
      parent. Diagnostic accuracy was greater than 99 per cent, taking into account the
      possibility of genetic heterogeneity.

PMID- 1355294
TI  - Etonitazene delivered orally serves as a reinforcer for Lewis but not Fischer 344
      rats.
AB  - Oral etonitazene self-administration was systematically investigated in two
      inbred strains of rats, Lewis (LEW) and Fischer 344 (F344). For LEW rats,
      etonitazene maintained higher rates of lever pressing and was consumed in larger
      volumes than the water vehicle when the reinforcement schedule was fixed ratio
      (FR) 8. In contrast, with F344 rats responding did not systematically exceed
      water values at any etonitazene concentration. LEW rats also drank substantially
      more etonitazene than F344 rats, and at FR 8 only LEW rats showed the typical
      inverted U-shaped function between etonitazene concentration and number of
      responses. For the LEW strain, response rate increased as FR size increased from
      FR 1 to FR 2 and FR 4, but decreased at FR 8. For the F344 strain, as FR size
      increased response rate showed small increases, but the response rates were far
      lower than those of the LEW strain. The results support the conclusion that
      etonitazene was an effective reinforcer for LEW but not F344 rats. These findings
      demonstrate genetic differences in opioid reinforcement of operant behavior and
      indicate that genotype can be an important determinant of whether etonitazene
      serves as a reinforcer.

PMID- 1355295
TI  - Effects of tizanidine on morphine physical dependence: attenuation and
      intensification.
AB  - It has previously been shown that subchronic and acute administration of L
      asparaginase and glutaminase inhibitors D-Aspartic acid (D-ASP) and prolyl-leucyl
      glycinamide (PLG) intensifies and attenuates morphine (M) physical dependence,
      respectively, by the inhibition of ASP and glutamic acid (GLU) production, and
      subsequently their normal releases. Tizanidine (TIZ) has long been known to be an
      alpha 2-adrenoceptor agonist and inhibitor of ASP and GLU release. Therefore, in
      this study TIZ has been administered subchronically during the development of M
      physical dependence to rats in which M-containing pellets had been implanted or
      acutely 30 min before naloxone (NL)-induced abstinence syndrome. The subchronic
      administration of TIZ intensified NL-precipitated abstinence syndrome whereas its
      acute administration attenuated it, as did D-ASP and PLG. On the other hand, TIZ
      added into the medium prevented the in vitro M-dependent-made guinea pig ileum
      from contracting following NL application. Furthermore, TIZ stopped the already
      started contraction by NL of the M-dependent ileum, which completely relaxed
      later. These effects of TIZ on M-dependent ileum were antagonized by the alpha 2
      adrenoceptor antagonist yohimbine. The intensification by subchronic TIZ
      administration of abstinence syndrome was attributed to the lesser release of ASP
      and GLU, which resulted in the larger blockade of M of ASPergic/GLUergic
      receptors due to the lesser release of their endogenous agonist ASP and GLU and
      consequently the higher upregulation of the receptors. The attenuation by acute
      TIZ administration of NL-precipitated abstinence syndrome was explained with
      lesser release of ASP and GLU and concomitantly the lesser stimulation of the
      receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355297
TI  - Sexual segregation in infancy and bi-directional benzodiazepine effects on hot
      plate response and neophobia in adult mice.
AB  - In the present experiment, the hypothesis that rearing animals in conditions of
      sexual segregation in infancy (ISS) would affect their adult behavioral
      reactivity to drug or environmental challenges was tested. Outbred Swiss CD-1
      mouse litters were reduced at birth to six pups according to three conditions: MM
      (all males), MF (sex-balanced composition), and FF (all females). At weaning (day
      21), all mice were rehoused in unisexual groups. At adulthood (day 70), animals
      were challenged either with BDZ agonist chlordiazepoxide (CDP at 2.5- or 5.0
      mg/kg dose) or BDZ receptor partial inverse agonist Ro 15-3505 (RO at 3-, 10-, or
      30-mg/kg dose) and assessed in sequence for pain reactivity in a hot-plate
      apparatus (set at 55 +/- 1 degrees C), for locomotor activity in a Varimex
      apparatus, and finally for neophobia level by measuring the latency to first
      approach a novel object. As concerns the hot-plate test, lick latency was
      significantly shortened in MF females receiving CDP (5.0 mg/kg), while RO was
      either ineffective in MF females or induced a prominent dose-dependent analgesia
      in FF females. Activity was decreased by CDP (2.5 mg/kg) and enhanced by RO (3.0
      mg/kg). For latency to approach a novel object, males as a whole exhibited
      shorter times than females. Mixed-sex animals of both sexes were less fearful,
      being also more explorative than their corresponding unisexually reared groups.
      In particular, MF males receiving either a 5.0-mg/kg CDP dose or a 3.0-mg/kg RO
      dose explored the object more often than MM males.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1355296
TI  - Dynorphin A(1-13) preferentially inhibits behaviors induced by the D2 dopamine
      agonist RU 24213 but not by the D1 dopamine agonist SK&F 38393.
AB  - The effects of dynorphin A(1-13) on the D1 dopamine agonist SK&F 38393- and the
      D2 dopamine agonist RU 24213-induced behavioral alterations in the mouse were
      determined by using multidimensional behavioral analyses based upon a capacitance
      system. Although dynorphin A(1-13) (3.0 or 12.5 micrograms) alone did not produce
      any significant effects on behaviors, the peptide (12.5 micrograms) caused an
      inhibitory effect on the RU 24213 (3.0 mg/kg)-induced increase in behavioral
      patterns such as linear locomotion and circling except rearing and grooming
      behaviors. The antagonistic effects of dynorphin A(1-313) (12.5 micrograms) were
      fully reversed by the opioid antagonist M(r) 2266 (10.0 mg/kg). However,
      dynorphin A(1-13) (3.0 or 12.5 micrograms) failed to affect behaviors elicited by
      SK&F 38393 (10.0 mg/kg). These results suggest that dynorphin A(1-13) plays an
      inhibitory role in behaviors induced by the D2 dopamine agonist but not by the D1
      dopamine agonist, possibly through the mediation of kappa-opioid receptors.

PMID- 1355299
TI  - Cognitive-behavioral therapy for benzodiazepine discontinuation in panic disorder
      patients.
AB  - The discontinuation of benzodiazepine treatment in patients with panic disorder
      may be associated with emergent withdrawal and anxiety symptoms, relapse of
      panic, and the inability to complete benzodiazepine taper. Although some patients
      may respond to slow taper strategies or the use of pharmacologic adjuncts, many
      continue to experience significant difficulties during benzodiazepine
      discontinuation. This paper presents a cognitive-behavioral conceptualization of
      benzodiazepine discontinuation difficulties, emphasizing "fear of fear" cycles.
      From this perspective the discontinuation process is seen as exposing panic
      disorder patients to somatic sensations associated with panic at a time when
      there is both increased anxiety and concern about re-emergence or worsening of
      panic episodes. As a consequence, patients may re-enter a cycle of catastrophic
      interpretations of symptoms, increased vigilance and fear, and panic. Cognitive
      behavioral interventions may ameliorate discontinuation-associated difficulties
      and prevent the return of the panic disorder. Preliminary data supporting the
      efficacy of these interventions are described.

PMID- 1355298
TI  - Effects of atipamezole, an alpha 2-adrenoceptor antagonist, on the performance of
      rats in a five-choice serial reaction time task.
AB  - The present study investigates whether pharmacological activation of the
      noradrenergic system improves attention. The effects of atipamezole, a potent
      alpha 2-adrenoceptor antagonist, on the performance of adult male rats in the
      five-choice serial reaction time task were studied. Before drug testings, food
      deprived rats were trained to detect and respond to brief flashes of light
      presented randomly by the computer in one of five spatially diverse locations
      until a stable level of performance had been reached (about 3 months). Single
      dose administration of atipamezole (0.03-3.0 mg/kg) slightly increased the number
      of premature and perseverative responses during the intertrial interval and
      slightly decreased the reaction times to incorrect responses, indicating
      increased behavioral activation. Atipamezole did not affect discriminative
      accuracy. However, in a subpopulation of rats with the poorest discriminative
      accuracy according to pretest performance seven of eight rats improved their
      discriminative accuracy when treated with 0.3 mg/kg atipamezole as compared to
      controls. At the other doses tested, no improvement was found. The present
      results suggest that acute administration of atipamezole, and alpha 2
      adrenoceptor antagonist, slightly increases behavioral activation, although the
      effects on baseline performance in the task measuring selective attention are
      modest.

PMID- 1355300
TI  - Schizophrenia and the D1 receptor: focus on negative symptoms.
AB  - Negative symptoms have been associated with structural impairment in the PFC, and
      hypothesized to arise from a central hypodopaminergic substrate. Corticofugal PFC
      neurons, which are inhibited by VTA DA innervation, exert a tonic excitatory
      modulation on DA activity in the NAS. Lesions of ascending DA forebrain
      projections "uncouple" the functional link between D1 and D2 receptors,
      permitting independent activation of D1 sites in generating behavioral output. A
      previously identified absence of this D1/D2 link in schizophrenic brain suggests
      that functional activation of PFC D1 receptors may induce hyperinhibition of
      descending corticofugal efferents to the NAS. Consequent hypoactivity of DA in
      the NAS is proposed to give rise to negative symptoms of schizophrenia, and low
      dose DA agonist treatments may mimic behavioral features of this symptom profile
      via direct PFC D1 stimulation. It follows that clozapine's efficacy for negative
      symptoms may be attributable, in part, to blockade of PFC D1 receptors, with
      subsequent enhancement of glutamate-facilitated NAS DA activity.

PMID- 1355301
TI  - The future of 5-HT1A receptor agonists. (Aryl-piperazine derivatives).
AB  - At present the dominant position among anti-anxiety medications has changed from
      meprobamate to the benzodiazepine derivatives. In order to avoid benzodiazepine's
      (BZ) undesirable side effects such as impairment of psycho-motor function, memory
      impairment, low dose dependence and withdrawal symptoms, a third generation
      anxiolytic agent, buspirone, the focus of the aryl-piperazine group of anti
      anxiety agents, has been introduced recently. Aryl-piperazine derivatives work as
      5-HT1A receptor partial agonists and are known as serotonin normalizers.
      Therefore, they are expected to have not only an anxiolytic function but also an
      anti-depressant effect as well. A characteristic of the aryl-piperazine
      derivatives is that they have no sedative and muscle relaxant effects, and they
      do not have BZ's undesirable side-effects, especially in regard to withdrawal
      symptoms. However they have a rather weak anxiolytic action and a slow onset of
      action. Aryl-piperazine derivatives will not take the place of BZ, but the use of
      BZ and buspirone as bridge medications, making the most of the strong points of
      both, can be proposed as a way to compensate for their respective clisadvantages.

PMID- 1355302
TI  - Regional glucose metabolism in schizophrenic patients before and during
      neuroleptic treatment.
AB  - Determination of regional glucose metabolism has been considered to be a tool to
      elucidate the mechanisms of action of neuroleptics. D2-dopamine antagonists seem
      to increase glucose consumption in dopamine innervated areas. Studies in humans
      do not give results in complete accordance with animal findings. In patients
      neuroleptic compounds and dopamine agonists probably increase and decrease
      striatal metabolism respectively. Changes in metabolism, especially in the right
      hemisphere may be coupled with improvement of the patients. Future research must
      be based on protocols specially designed for the study of drug effects.

PMID- 1355303
TI  - Early serum levels of neuroleptics do not predict therapeutic response in
      schizophrenia.
AB  - Thirty-six acute schizophrenics were included in a 28-day open treatment study
      with the neuroleptic perazine. Peak serum levels of parent drug and its main
      inactive metabolite desmethyl-perazine were assessed 2 hours after an oral test
      dose given at the beginning of the study. Whereas peak levels of perazine were
      not significantly different in treatment responders and nonresponders, desmethyl
      perazine was significantly higher in nonresponders. The ratio between desmethyl
      perazine and perazine was not predictive of (non-) response to neuroleptic
      treatment in schizophrenia.

PMID- 1355304
TI  - 1st Lox-Workshop. A symposium: Long term portable oxygen treatment in severe
      disabled COPD?--Rational and study design. Berlin, November 23, 1990.

PMID- 1355305
TI  - [Cancer, AIDS and society].

PMID- 1355306
TI  - Identification of genetic susceptibility loci for insulin-dependent diabetes in
      Sudan.
AB  - In this study we report, for the first time, the molecular analysis of HLA-DR and
      DQ gene frequencies in a large cohort of well-characterized type 1 (insulin
      dependent) diabetes mellitus (IDDM) patients (n = 72), and ethnically matched
      controls (n = 59) collected in sub-Saharan Africa. High molecular mass DNA was
      prepared and analysed in Southern blots and by oligonucleotide typing. We have
      shown a strong positive association between IDDM and the Asp 57- DQB1 allele
      *0201 (DQw2). A rare DR4, DQw2 haplotype was also identified at high frequency in
      the IDDM cohort. We can now confirm that the association between Asp 57- DQB1
      alleles and IDDM, previously reported in ethnically diverse cohorts collected in
      Western Europe, North America, and South Asia, is also present in an IDDM cohort
      collected in Africa.

PMID- 1355308
TI  - Suppression of T-cell responsiveness during tsetse-transmitted trypanosomiasis in
      cattle.
AB  - In the present study, we demonstrate that lymph node cells from cattle infected
      with T. congolense through tsetse fly challenge were unable to proliferate in
      vitro following activation with the T-cell mitogen Concanavalin A. This was
      associated with a simultaneous suppression of interleukin 2 (IL-2) production and
      interleukin 2 receptor (IL-2R) expression. However, the capacity of the cells to
      secrete interferon gamma following the mitogenic activation was not affected by
      the infection.

PMID- 1355309
TI  - Occupational epidemics in the 1990s. 5th US-Finnish joint symposium on
      occupational safety and health. Cincinnati, Ohio, June 9-12, 1992.

PMID- 1355307
TI  - Experimental infection with a haemorrhage-causing Trypanosoma vivax in N'Dama and
      Boran cattle.
AB  - N'Dama cattle control experimental infections with clones of Trypanosoma
      congolense of varying degrees of virulence, but nothing is known about their
      capacity to control infections caused by highly virulent, East African stocks of
      T. vivax. Thus four N'Damas and four trypanosusceptible Borans were infected with
      a tsetse-transmitted stock of T. vivax IL2337. In Ayrshire cattle this stock is
      known to cause severe haemorrhagic disease. No differences were observed in the
      parasitaemia between the two groups. Both groups became anaemic. The mean packed
      cell volume fell to 16.8 +/- 5.0% in the N'Dama cattle and to 24.2 +/- 2.2% in
      the Borans on day 26 post infection. These differences were not significant.
      Antibody responses to invariant trypanosome antigens were analysed. No
      differences were observed between the groups in the pattern of recognition or the
      isotype elicited. Antibody bound to the surface of erythrocytes was occasionally
      detected. No anti-platelet activity was observed. The results show that N'Dama
      cattle, which are known to be resistant to disease caused by T. congolense and by
      T. vivax stocks from West Africa, were highly susceptible to an infection of T.
      vivax which causes acute haemorrhagic disease.

PMID- 1355310
TI  - Arctic terrestrial ecosystem contamination.
AB  - Limited data have been collected on the presence of contaminants in the Arctic
      terrestrial ecosystem, with the exception of radioactive fallout from atmospheric
      weapons testing. Although southern and temperate biological systems have largely
      cleansed themselves of radioactive fallout deposited during the 1950s and 1960s,
      Arctic environments have not. Lichens accumulate radioactivity more than many
      other plants because of their large surface area and long life span; the presence
      and persistence of radioisotopes in the Arctic is of concern because of the
      lichen----reindeer----human ecosystem. Effective biological half-life of cesium
      137 is reckoned to be substantially less than its physical half-life. The
      database on organochlorines in Canadian Arctic terrestrial mammals and birds is
      very limited, but indications are that the air/plant/animal contaminant pathway
      is the major route of these compounds into the terrestrial food chain. For
      terrestrial herbivores, the most abundant organochlorine is usually
      hexachlorobenzene followed by hexachlorocyclohexane isomers. PCB accumulation
      favours the hexachlorobiphenyl, pentachlorobiphenyl and heptachlorobiphenyl
      homologous series. The concentrations of the various classes of organochlorine
      compounds are substantially lower in terrestrial herbivore tissues than in marine
      mammal tissues. PCBs and DDT are the most abundant residues in peregrine falcons
      (a terrestrial carnivore) reaching average levels of 9.2 and 10.4 micrograms.g-1,
      respectively, more than 10 times higher than other organochlorines and higher
      than in marine mammals, including the polar bear. Contaminants from local sources
      include metals from mining activities, hydrocarbons and waste drilling fluids
      from oil and gas exploration and production, wastes from DEW line sites,
      naturally occurring radionuclides associated with uranium mineralization, and
      smoke containing SO2 and H2SO4 aerosol from the Smoking Hills at Cape Bathurst,
      N.W.T.

PMID- 1355311
TI  - Human brainstem auditory-evoked potentials in deep experimental diving to
      pressures up to 62.5 bar.
AB  - The neural mechanisms underlying the high pressure neurologic syndrome (HPNS),
      which limit man's safe advance to extreme diving depths, are still unclear. This
      work was aimed at a better understanding of HPNS through study of brainstem
      auditory-evoked potentials (BAEP). BAEP were repeatedly recorded within 2
      experimental chamber dives, Titan VIII (2 divers, maximum depth of 560 msw,
      compression time to bottom 109 h) and Titan XI (3 divers, maximum depth of 615
      msw, compression time to bottom 240 h). Prolongation of the IV/V-complex occurred
      in 2 divers upon reaching 525 msw during Titan VIII compression and was
      accompanied by vestibular disturbances and amplitude increases of finger tremor.
      Both categories of changes--clinical signs and IV/V delay--gradually diminished
      during a 4-day stay at 545 msw, suggesting that they depended on excessive
      compression rates and insufficient acclimation time. Longer holding times at
      intermittent depths during Titan XI clearly reduced both HPNS symptoms and
      magnitude of prolongation of IV/V latencies. Wave I and wave III latency did not
      significantly change, pointing to a suppression of pontomesencephalic
      transmission. We infer that pressure suppresses synaptic transmission or triggers
      an increase of cortical or subcortical efferent inhibitory modulation of upper
      pontine and midbrain auditory afferents. Postdive controls revealed no persistent
      changes of BAEP measures in either the Titan VIII or XI divers.

PMID- 1355312
TI  - Cerebral blood flow distribution during exposure to 5 bar oxygen in awake rats.
AB  - The regional cerebral blood flow (rCBF) and cardiac output (CO) were measured in
      conscious rats by the microsphere method during control, after 5 and 60 min at 5
      bar O2, and 5 min after decompression to air. The arterial acid-base balance was
      essentially unchanged during hyperbaric O2 and after decompression, except for a
      slightly reduced CO2 and HCO3 during the O2 exposure. The heart rate (HR) fell at
      1 bar O2, continued to fall during compression, and remained low. A marked HR
      rise occurred in air after decompression. The systolic arterial pressure (AP)
      increased, while mean AP was constant during the O2 exposure. The CO and total
      cerebral blood flow fell in proportion to the arterial O2 content increase. The
      rCBF was unevenly distributed in control, and fell to a disparate degree and
      remained low in some regions during O2 exposure. Due to the rCBF fall, the O2
      supply was limited, the glucose supply was reduced, and CO2 and heat transport
      probably were limited, suggesting a labile metabolic state locally in the brain.
      After decompression, blood flow remained low in several regions, making hypoxia
      likely for a considerable time in several brain areas, whereas the rest of the
      brain had normalized or increased blood flow. The HR and systolic AP remained
      high for at least 30 min after decompression.

PMID- 1355313
TI  - Xenon washout from the rabbit femur during short hyperbaric exposures.
AB  - 133Xenon washout from the femora of 5 anesthetized rabbits was recorded during
      short hyperbaric exposures (3 atm abs). Equipment tests showed that the
      scintillation counter was heat sensitive. The recorded count rate from a constant
      source of 133xenon decreased during compression (temperature rose 5 degrees C)
      and increased during decompression (temperature fell 5 degrees C). When the
      scintillation counter was thermally insulated, the rate of xenon washout from the
      femur remained unchanged in all rabbits during these hyperbaric exposures. The
      conclusion is that the rate of xenon washout from the femur is not affected by
      changes in ambient pressure. As most scintillation counters are heat sensitive,
      it is possible that the previous report of such changes was erroneous and caused
      by heat sensitivity of the recording equipment.

PMID- 1355314
TI  - Intravascular bubble composition in guinea pigs: a possible explanation for
      differences in decompression risk among different gases.
AB  - Differences in risk of decompression sickness (DCS) that have been observed among
      inert gases may reflect differences in gas solubility or diffusivity or both. A
      higher risk gas might generate a larger volume of evolved gas during
      decompression, thereby increasing the probability of DCS. If this hypothesis is
      correct, the composition of bubbles that develop during decompression should
      reflect such gas differences. Unanesthetized guinea pigs were compressed to
      depths ranging from 250 to 350 fsw with air, He-O2 (21% O2) or one of a number of
      N2-He-O2 or N2-Ar-O2 mixtures (21% O2). Animals were held at depth from 15 to 60
      min, then decompressed slowly (60 fsw/min) or rapidly (less than 15 s) to 5 fsw.
      If severe DCS developed, as judged by changes in physiologic variables, death
      usually occurred quickly. Gas/blood samples were then immediately withdrawn from
      the right atrium or the inferior vena cava, and the gas phase analyzed for He,
      N2, Ar, O2, and CO2 via gas chromatography. Bubbles from all dives contained 5-9%
      CO2, 1-4% O2, with the balance inert gas. Bubbles after N2-He-O2 dives contained
      substantially more N2 than He (up to 1.9 times more) compared to the dive
      mixture; bubbles after N2-Ar-O2 dives contained more Ar than N2 (up to 1.8 times
      more). For N2-He-O2 dives, the actual inert gas makeup of bubbles was dependent
      on the time-at-depth and the decompression profile. Results may reflect
      differences among He, N2, and Ar in tissue solubility/diffusivity and gas
      exchange rates, and support the rank order of increasing DCS risk (He less than
      N2 less than Ar) and rate of gas exchange (N2 less than He) observed previously
      during rat dives.

PMID- 1355315
TI  - Rift Valley fever virus activity in East Africa in 1989.

PMID- 1355316
TI  - Comparative bacteriological studies on summer mastitis in grazing cattle and
      pyogenes mastitis in stabled cattle in Denmark.
AB  - A total of 143 secretions from clinical cases of summer mastitis (SM) in grazing
      cattle and from 89 cases of pyogenes mastitis (PM) in stabled cattle were
      examined bacteriologically. The typical bacteriological finding was a mixed flora
      in which the predominant organisms were Actinomyces pyogenes (SM-70%, PM-85%),
      Peptostreptococcus indolicus (54%, 54%), a microaerophilic coccus (Stuart-Schwan
      coccus) (26%, 25%), Fusobacterium necrophorum biovar B (22%, 12%), Bacteroides
      melaninogenicus (20%, 9%) and Streptococcus dysgalactiae (21%, 5%). All except
      six cases occurred in non-lactating animals or within three weeks after
      parturition. The majority of animals (about 90%) had only one quarter affected
      and no differences in quarter distribution were observed between the two groups.

PMID- 1355317
TI  - Identification of canine T-lymphocyte subsets with monoclonal antibodies.
AB  - A panel of five murine monoclonal antibodies to canine T-lymphocytes were
      produced. Antibodies 4.78, 12.125 and 8.358 reacted with approximately 18%, 39%
      and 60% peripheral blood lymphocytes, respectively. Two color flow cytometric
      analysis showed that lymphocytes expressing 1.140, 4.78, 8.53 and 12.125 were
      subsets of lymphocytes expressing 8.358. The lymphocytes expressing 8.358 were
      negative for surface immunoglobulin. The subsets defined by 1.140, 4.78 or 8.53,
      12.125 were mutually exclusive and together account for most cells expressing
      8.358 in the peripheral blood, spleen, and lymph node. In the thymus,
      approximately 47% cells were positive for both 1.140/4.78 and 8.53/12.125. SDS
      PAGE analysis of radiolabelled thymus cell lysates demonstrated that antibodies
      1.140 and 4.78 immunoprecipitated a 32,35 kd heterodimer under reducing
      conditions and 12.125 immunoprecipitated a single 56 kd chain under reducing and
      non-reducing conditions. Antibodies 8.53/12.125 and 1.140/4.78 react with canine
      lymphocyte populations that occur in proportions similar to lymphocytes
      expressing CD4 and CD8 like molecules in several primate and non-primate species.
      The molecules recognized by 12.125 and 1.140/4.78 were similar in size and
      subunit composition to human CD4 and CD8.

PMID- 1355318
TI  - Development of the B- and T-cell compartments in porcine lymphoid organs from
      birth to adult life: an immunohistological approach.
AB  - Using immunohistological techniques, we studied the development over time of B-
      and T-cell compartments in the lymphoid organs of specific-pathogen-free pigs.
      Tissue samples were collected at various time-points, starting 2 days before the
      pigs were born until the pigs were 10 months old. The samples were collected from
      the spleen, thymus, peripheral lymph node, mesenteric lymph node, duodenum,
      jejunum, ileum, jejunal Peyer's patch and ileal Peyer's patch. Monoclonal
      antibodies specific to B- and T-cells were used to identify where the following
      cells were localized: IgM-B cells (cells positive to surface immunoglobulin), IgM
      , IgG- and IgA-containing cells (cells positive to cytoplasmic immunoglobulin),
      and CD2-, CD4- and CD8-positive cells. The development of the B- and T-cell
      subpopulations in each organ was analysed. Two days before birth, most organs
      contained quantities of IgM-B cells. The spleen, lymph nodes, Peyer's patches
      and, notably, the thymus, contained some immunoglobulin-containing cells (Ig-CC);
      this finding indicates that pigs have cells that secrete immunoglobulins before
      birth. Just after birth, the incidence of Ig-CC increased in most organs; first
      IgM-CC increased, then either IgG- or IgA-CC increased, depending on the organ. T
      cell development was observed clearly in spleen and in the lamina propria of the
      small intestine, in contrast to other organs, in which the T-cell compartments
      containing various T-cell subpopulations were well developed before birth.
      Comparison of the incidence of CD4+ and CD8+ cells showed that the CD4:CD8 ratio
      of these cells in the spleen, lymph nodes, Peyer's patches and small intestine is
      low, especially in adult pigs, compared with the CD4:CD8 ratio in other species.
      Weaning had little influence on the incidence of B- and T-cells in lymphoid
      organs. This study is the first immunohistological survey to describe the
      development of the major B- and T-cell subpopulations in various lymphoid organs
      of pigs, and it should be useful for future immunopathological and comparative
      immunological studies in pigs.

PMID- 1355319
TI  - Induction of interdigitating reticulum cell-like differentiation in human
      monocytic leukemia cells by conditioned medium from IL-2-stimulated helper T
      cells.
AB  - Monocytic leukemia (MoL) cells were obtained from the peripheral blood of a
      patient in whom the leukemic cells infiltrating various lymphoreticular organs
      exhibited features intermediate between interdigitating reticulum cells (IDC) and
      ordinary phagocytic macrophages, whereas the leukemic cells in the peripheral
      blood were essentially monocytic and lacked such features. Peripheral blood CD4+
      T-cells were established as an interleukin-2-dependent T-cell line. When the MoL
      cells were exposed for a few days to conditioned medium from the T-cell line,
      they extended several dendritic cytoplasmic projections and became intensely
      positive for HLA-DR antigen, cytoplasmic S-100 beta protein, and CD1 antigen.
      Functionally, the conditioned medium significantly down-regulated Fc-mediated and
      Fc-independent phagocytic activities, and the levels of lysosomal enzymes such as
      lysozyme and nonspecific esterase in the MoL cells. Moreover, the conditioned
      medium significantly up-regulated the accessory cell function of the MoL cells as
      measured by the primary allogenic mixed leukocyte reaction (MLR). Furthermore,
      the conditioned medium significantly down-regulated the expression of CD14
      antigen. Biochemical analysis indicated that the factor responsible for these
      changes is a protein which is distinct from known human cytokines and whose
      molecular weight is approximately 31 kDa. These findings suggest that IDC are
      closely related the monocytic lineage and that helper T-cells play an important
      role in constructing the microenvironment of T-lymphoid tissues which is
      necessary for the differentiation and maturation of IDC.

PMID- 1355320
TI  - Immune-mediated interactions during macrophage development in non-Hodgkin's
      lymphoma.
AB  - As part of an investigation of mononuclear phagocytes in malignant lymphoma,
      measurement of immune-mediated erythrophagocytosis and rosette formation was
      carried out on cells grown in suspension culture at the monocyte (Day 0) and
      macrophage (Day 6) stages; the culture medium contained autologous serum. Cells
      were derived from 10 patients with untreated non-Hodgkin's lymphoma (NHL) and
      from 12 normal individuals. The results were subjected to Analysis of Variance
      and demonstrated a significant difference between the two groups with respect to
      erythrophagocytosis but not to rosette formation. In the NHL group, the
      proportion of erythrophagocytic cells showed no significant increase between the
      monocyte and macrophage stages (0.07 to 0.09), in contrast to the marked increase
      seen in the normal group (0.09 to 0.24). In a pilot investigation to examine the
      possible role of factors in the serum, cells derived from the NHL patients were
      cultured with serum from healthy donors; they showed no significant difference in
      the immune-mediated functions from those grown in autologous serum. Overall, the
      results provide further quantitative evidence of defective macrophage maturation
      in NHL, presumably reflecting the compromise of host defence mechanisms.

PMID- 1355321
TI  - Novel, contrast gradient-oriented, automated chromatin texture analysis. I.
      Feasibility study on nuclei from benign and malignant breast epithelial cell
      lines in fine needle aspirates.
AB  - Coarse granularity of nuclear chromatin texture is a prominent feature of most
      malignant cell lines. We have chosen the abrupt transition from eu- to
      heterochromatic foci (high contrast gradient [CG]) as a novel parameter for
      coarseness. This feature was quantified using automated image analysis of single
      nuclei in smears stained by the May-Grunwald-Giemsa technique. The principle of
      this approach consists of eliminating, with the help of subtraction between two
      image lowpass filters, the small grey level differences among pixels, so that
      only high CG values are retained on the digitized image. The sum of these
      distinctive microareas is then taken as a fraction of the area of the
      peripherally eroded nucleus, and this ratio is designated as contrast gradient
      index (CGI) per nucleus. This method was tested on fine needle aspirates from 11
      patients with benign breast disease (BBD) and 14 with mammary carcinoma (CA). For
      each specimen, 60 nuclei were analyzed, with a measuring time per nucleus of
      about 1 min. A high significant distinction between epithelial cell populations
      in BBD and CA, respectively, was obtained by variance analysis of all CGIs per
      nucleus (p = 2 x 10(-18). The median and the mean values of CGI per specimen were
      the next best discriminators, followed by the modes and the standard deviation of
      CGI per specimen. The percentage of nuclei per specimen with CGI values of
      greater than 12 was also significantly greater in CA than in BBD.

PMID- 1355322
TI  - Abnormal increase in multinuclear macrophages in primary cultures of BUF/Mna rat
      thymomas.
AB  - The in vitro characteristics of spontaneous thymomas from BUF/Mna rats, a strain
      with a high incidence of these tumors, were studied. In primary cultures, the
      adherent cells consisted of mononuclear macrophages, mono- and multi-nuclear
      epithelial cells and some fibroblastic cells on day 3. The macrophages rapidly
      increased in number with the formation of large multinuclear cells by day 9. A
      modest increase in the number and nuclearity of macrophages was also noted in
      adherent cultures of normal thymuses from 5-week-old BUF/Mna rats. On the other
      hand, in cultures of thymic cells from 1-year-old or 5-week-old ACI/NMs rats, a
      normal control rat strain, macrophages did not increase in number and only rarely
      formed multinuclear cells in adherent cell cultures. These results suggest that
      abnormal proliferation signal(s) to thymic macrophages and/or their progenitor
      cells accompanies and may be involved in the development of thymomas in BUF/Mna
      rats.

PMID- 1355323
TI  - Emperipolesis of lymphoid cells by human follicular dendritic cells in vitro.
AB  - Isolated follicular dendritic cells (FDCs) showed true and pseudoemperipolesis of
      fresh tonsillar lymphocytes, even after long-term (50-day) cultivation.
      Emperipolesis by FDCs was not restricted by allotype specificity, nor was it
      inhibited by the addition of antibodies against MHC-I & II antigens. Follicular
      dendritic cells predominantly engulfed B-cells; monocytes and macrophages were
      not found between FDC cytoplasmic extensions. When highly purified T-cell
      populations were added to FDC cultures emperipolesis of T-cells occurred,
      particularly those of the CD4-positive phenotype. Mitoses appeared within 6 h in
      the emperipolesed lymphocytes and, after an additional 18 h, some lymphocytes
      exhibited apoptosis.

PMID- 1355324
TI  - Blood group antigen expression in medullary carcinoma of the thyroid. An
      immunohistochemical study on the occurrence of type 1 chain-derived antigens.
AB  - Using monoclonal antibodies (MoABs) against blood group determinants and related
      carbohydrate sequences, it is now possible to clarify their carcinoma-associated
      modulation at a molecular level. In the present study a panel of MoABs against
      different type 1 chain derived blood group antigens, comprising A, B, H type 1,
      Le(a), sialyl-Le(a) (CA 19-9), sialyl type 1 structure (CA 50), and Le(b) was
      used to investigate their immunoreactivity in 38 medullary carcinomas of the
      thyroid (MTC) and in normal thyroid tissue. The antigens were not expressed in
      normal follicular or C-cells but were expressed to a various extent in MTC. The
      studies revealed some characteristic anomalies in the frequency and patterns of
      tumor-associated antigen expression. The MoAB C 50 stained 32 of the 38 tumors, H
      type 1 (Le(d)) was demonstrated in 21 and the Le(b) antigen in 27. The Le(a)- and
      the A antigen were detected in 10 and 12 tumors and the B antigen in one. From
      the results some rules about the pathways for tumor-associated re-expression of
      these antigens can be deduced. Le(a) antigen expression was significantly
      correlated with the CA 50 and Le(b) antigens. The significant relation observed
      between A-, H1-, and Le(b) antigen formation in MTC suggests the existence of a
      carcinoma-associated fucosyltransferase committing the type 1 precursor chain
      along the H1-antigen pathway, and by further glycosylation to an A-, B-, or a
      Le(b) antigen. Comparative studies of tumor-associated H type 1 and H type 2
      antigen expression revealed that H type 2 antigen synthesis was significantly
      related to a blood type 0 in the host. On the other hand, H1 antigen reactivity
      was independent of the AB0 blood type of the hosts and was also detected in H
      type 2 antigen-negative tumors. These findings support the proposal that even in
      tumor tissue, H antigen expression is still determined by the interaction of at
      least two different genes. Despite the occurrence of the precursor substance (CA
      50) and the formation of the Le(a)- and Le(b) antigens, indicating the presence
      of a alpha 1,4-fucosyl-transferase (Lewis-enzyme), only two tumors showed the
      formation of CA 19-9. In conclusion, the investigations demonstrated the dominant
      re-expression of three type 1 chain-derived structures in MTC, namely H type 1,
      Le(b), and CA 50. These findings support the general concept demonstrated in
      other carcinomas, that fucosyl- and sialyltransferases are preferentially
      activated in MTC.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1355326
TI  - [24-hour blood pressure monitoring. Workshop. Gottingen, 24-25 January 1992].

PMID- 1355327
TI  - [Return of circadian blood pressure and heart rate changes in patients with heart
      transplants].
AB  - A loss of the circadian rhythm pattern of blood pressure (BP) and heart rate, as
      well as the development of hypertension have been found after heart
      transplantation (Htx). To study whether a return of this rhythm occurs in the
      long-term after Htx, we used 24-h ambulatory monitoring to study 62 patients 5
      days to 6.5 years after Htx. Patients were divided into two groups (Group 1: less
      than 6 months after Htx (n = 30), Group 2: 6 months or more after Htx (n = 32)).
      Group 2 had a higher BP and heart rate, as well as a significantly higher
      difference between systolic day and systolic night BP than group 1. There was
      also a significantly higher difference in heart rate between day and night values
      in group 2. The return of the circadian rhythm pattern in the longer term after
      heart transplantation may result from partial reinnervation of the heart,
      although other neurohumoral factors or concomitant medication may play a role.

PMID- 1355325
TI  - Eosinophilic globule cells in mouse MFH-like sarcomas: lectin histochemistry.
AB  - Lectin binding patterns in ten mouse malignant fibrous histiocytoma (MFH)-like
      sarcomas containing eosinophilic globule (EG) cells and in granular metrial gland
      (GMG) cells of mouse placenta were stained with nine lectins (Con A, LCA, WGA,
      DBA, SBA, e-PHA, PNA, RCA-I and UEA-I) by an avidin-biotin-peroxidase-complex
      method. EG cells stained strongly with DBA, SBA and PNA which are specific for N
      acetyl-D-galactosamine and/or D-galactose. DBA and SBA bound throughout the
      cytoplasm including the globules; PNA reacted preferentially at the cell surface.
      There was no evidence that these three lectins were reactive for immature EG
      cells. WGA, RCA-I and e-PHA also gave a slightly to moderately positive reaction
      to globules of EG cells. The results indicate that the globules contain abundant
      O-linked sequences of sugars, but also a few N-linked residues. MFH tumor cells
      showed a variable degree of binding with Con A, RCA-I, and WGA, but did not react
      with DBA, SBA and PNA. On the other hand, GMG cells exhibited specific affinities
      for DBA, SBA and PNA with staining patterns similar to those of EG cells. These
      findings suggest that EG and GMG cells may be of the same cellular lineage.

PMID- 1355329
TI  - European Society for Stereotactic and Functional Neurosurgery, 10th Congress.
      Stockholm, Sweden, September 2-5, 1992. Abstracts.

PMID- 1355328
TI  - Control of peroxisome proliferation in Saccharomyces cerevisiae by ADR1, SNF1
      (CAT1, CCR1) and SNF4 (CAT3).
AB  - The Saccharomyces cerevisiae ADR1 gene has recently been demonstrated to control
      transcription of several genes encoding peroxisomal proteins or proteins
      necessary for peroxisome formation. Therefore, the effect of two other genes
      (SNF1 (CAT1, CCR1) and SNF4 (CAT3)) known to control derepression of glucose
      repressible genes was studied. Levels of transcripts of genes encoding catalase
      A, fatty acid beta-oxidation enzymes and of the PAS1 gene are reduced in snf1 and
      snf4 mutants on ethanol as well as on oleic acid medium. By immunogold labelling
      with an antibody directed against peroxisomal thiolase, clusters of peroxisomes
      were detected in wild-type cells, whereas smaller single peroxisomes were
      observed in adr1 mutant cells. Results of immunofluorescence experiments are
      consistent with these observations. No peroxisomes were detected in snf1 and snf4
      mutants by immunogold labelling as well as by immunofluorescence.

PMID- 1355330
TI  - Proceedings of the Eastern Pennsylvania Branch of the American Society for
      Microbiology Symposium of Innovations in Antiviral Development and the Detection
      of Virus Infections. Philadelphia, November 15-16, 1990.

PMID- 1355331
TI  - Elimination kinetics of maternally derived thyrotropin receptor-blocking
      antibodies in a newborn with significant thyrotropin elevation.
AB  - OBJECTIVE: To determine the course of maternally derived elevations in
      thyrotropin-binding inhibitory immunoglobulins in a neonate. DESIGN: Case report.
      SETTING: University pediatric endocrinology clinic and endocrine immunology
      laboratory in Ohio. PARTICIPANTS: An infant with elevated thyrotropin levels but
      near-normal total thyroxine levels, and her mother. INTERVENTIONS: None.
      MEASUREMENTS/MAIN RESULTS: Thyroid hormone, thyrotropin, and thyrotropin-blocking
      immunoglobulin concentrations were serially measured in a woman and her infant,
      who was found to have elevated thyrotropin levels (234 mU/L) and borderline low
      thyroxine levels (95 nmol/L). As infant thyroxine concentrations remained normal
      (125 to 145 nmol/L), no thyroxine supplementation was given. Thyrotropin levels
      decreased concomitantly with thyrotropin-blocking inhibitory immunoglobulin
      levels, and normalized by day 56 of life. The apparent elimination half-life of
      thyrotropin-blocking immunoglobulins was 7.5 days. CONCLUSIONS: The observed
      parallel elimination kinetics suggest that the thyrotropin receptor antibody acts
      as a thyrotropin antagonist, resulting in compensatory thyrotropin elevations.
      The duration of such elevations may be predicted on the basis of such
      elimination.

PMID- 1355332
TI  - Atrial natriuretic peptide-induced inhibition of aldosterone secretion: a quest
      for mediator(s)
AB  - Atrial natriuretic peptide (ANP) inhibits aldosterone secretion evoked by its
      physiological secretagogues by a mechanism(s) likely to involve intracellular
      messengers. When one examines the results of various investigations so far, this
      premise, although not definitive yet, seems to be supported. Therefore a brief
      perspective on the cellular messengers of the various secretagogues is provided
      before the inquiry into the possible mechanism of action of ANP. The receptors of
      ANP in the adrenal cells have been identified and characterized. ANP inhibits
      adenylate cyclase in various tissues through an inhibitory G protein, which
      appears to explain in part the inhibitory effect of ANP on adrenocorticotropin
      induced aldosterone secretion. However, there could be other possible effects of
      ANP as discussed. ANP probably inhibits aldosterone secretion evoked by
      angiotensin II and potassium by interfering with the appropriate changes in
      calcium flux and cell calcium concentration, concomitants of stimulation by these
      secretagogues. The potential modes of these effects are probed. The role of
      guanosine 3',5'-cyclic monophosphate, which is increased by receptor activation
      of guanylate cyclase by ANP and is thought to play a major role in the biological
      effects of ANP in some other tissues, remains controversial in the aldosterone
      lowering effect of ANP, and this is also discussed extensively in this review.

PMID- 1355333
TI  - Differential collagen and fibronectin production by Thy 1+ and Thy 1- lung
      fibroblast subpopulations.
AB  - Pulmonary fibrosis resulting from diverse etiologies is characterized by
      proliferation of fibroblasts and excessive accumulation of interstitial collagen.
      Whether fibrosis is associated with selective expansion of fibroblast
      subpopulations differing in amounts or types of collagens synthesized is unknown.
      We have previously isolated lines and clones of normal murine lung fibroblasts
      based on the presence of the Thy 1 surface antigen. These subpopulations differ
      in morphology, growth characteristics, and display of class II major
      histocompatibility complex antigens (R.P. Phipps, D.P. Penney, P. Keng, H. Quill,
      A. Paxhia, S. Derdak, and M. E. Felch. Am. J. Respir. Cell Mol. Biol. 1: 65-74,
      1989). We evaluated the amounts and types of collagen and fibronectin synthesized
      by Thy 1+ (Fib2-T-3+) and Thy 1- (Fib2-T-4-) lung fibroblast lines and clones.
      Thy 1+ fibroblast line synthesized two- to threefold more collagen and
      noncollagen protein than the Thy 1- line. In contrast, both the Thy 1+ and Thy 1-
      lines synthesized similar amounts of fibronectin. Thy 1+ and Thy 1- lines and
      clones expressed mRNA for alpha 1(I)-and alpha 1(III)-procollagen and synthesized
      both types (predominantly type I and lesser amounts of type III) of collagen,
      protein, and mRNA. The fibroblast clones varied significantly in total collagen
      and fibronectin production, with one Thy 1- clone (D3) synthesizing the largest
      amount of collagen but relatively little fibronectin.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1355334
TI  - Monoaminergic and cholinergic synaptic markers in the nucleus basalis of Meynert
      (nbM): normal age-related changes and the effect of heart disease and Alzheimer's
      disease.
AB  - Neurotransmitter markers for acetylcholine, serotonin (5-HT), and dopamine (DA)
      were measured in autopsied human nucleus basalis of Meynert (nbM) from
      nondemented individuals without heart disease (non-HD) (age range, 4-84 years; n
      = 77), nondemented individuals with heart disease (HD) (age range, 57-92 years; n
      = 23), and individuals with Alzheimer's disease (AD) (age range, 59-92 years; n =
      22). No significant differences in any chemical marker were found between age
      matched HD and non-HD individuals. The activities of choline acetyltransferase
      (ChAT) and acetylcholinesterase (AChE), and [3H]spiperone binding were regionally
      distributed within the nbM in control (non-HD) subjects less than 54 years of
      age. The activity of AChE, 5-[3H]HT binding, and the content of homovanillic acid
      (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 5-HT were regionally distributed
      in the nbM in non-HD, HD, and AD subjects more than 54 years of age. The binding
      of [3H]spiperone was regionally distributed in the nbM in HD and AD subjects more
      than 54 years of age, only. Activity of ChAT and AChE, content of 5-HT, 5-HIAA,
      and DA, binding of 5-[3H]HT, and the turnover number for DA (ratio of HVA/DA) all
      decreased with increasing age in the non-HD control population. The content of
      HVA, binding of [3H]spiperone, and the turnover number for 5-HT (ratio of 5
      HIAA/5-HT) did not change with increasing age. Significant reductions in ChAT and
      AChE activities were found in AD nbM compared with postmortem interval- and age
      matched HD and non-HD individuals. The reduction of 5-HT and 5-HIAA content and
      [3H]spiperone binding in individuals with AD of all ages suggests a loss of
      functional serotonergic innervation of the nbM. Dopaminergic synaptic markers
      were less affected in AD nbM, although turnover numbers for both DA and 5-HT were
      increased in AD. Receptor upregulation in response to presynaptic deficits did
      not occur for DA or 5-HT.

PMID- 1355335
TI  - Startle disease, or hyperekplexia: response to clonazepam and assignment of the
      gene (STHE) to chromosome 5q by linkage analysis.
AB  - Familial startle disease (also known as hyperekplexia and congenital "stiff-man"
      syndrome) is an autosomal dominant disorder characterized by an exaggerated
      startle reaction of sudden, unexpected auditory or tactile stimuli; affected
      neonates also have severe and occasionally fatal hypertonia. We recently
      encountered a large, five-generation family with startle disease, and treated 16
      patients (including 1 neonate) with clonazepam; all experienced dramatic and
      sustained improvement. We performed systematic linkage analysis in this family,
      and found tight linkage between the disease locus and a polymorphic genetic
      marker locus (colony-stimulating factor receptor, or CSF1R) that has been
      physically mapped to chromosome 5q33-q35. The maximum odds ratio favoring linkage
      over nonlinkage is greater than 10,000,000:1 (lod score, 7.10) at 3%
      recombination. Several genes encoding neurotransmitter receptor components have
      been physically mapped to the subtelomeric region of chromosome 5q, and are thus
      candidates for the startle disease gene. The availability of additional large
      pedigrees with startle disease should facilitate identification and
      characterization of the gene for this disorder.

PMID- 1355336
TI  - Overexpression of erbB-2 protein in gastric adenocarcinoma--a potential role in
      therapeutic response to adjuvant 5-FU-doxorubicin regimen.
AB  - In order to study the influence of erbB-2 protein overexpression on outcome of
      patients with gastric cancer after attempted curative resection with or without
      adjuvant chemotherapy, paraffin embedded sections from 109 cases of primary
      gastric cancer with defined treatments have been immunostained for erbB-2 protein
      in a retrospective study. Thirty four cases (31%) showed strong membrane staining
      of tumor cells. erbB-2 overexpression did not show significant effect on outcome
      when all patients were considered. However, erbB-2 overexpression was an
      indicator for poor disease free survival (p = 0.0474), local relapse free
      survival (p = 0.0293), and overall survival (p = 0.0310) of the patients treated
      with surgery only (N = 51), while it did not show any effect on outcome of
      patients treated with 5-FU plus Doxorubicin (FA) as adjuvant chemotherapy (N =
      58). Furthermore, the apparent therapeutic benefit from FA regimen was restricted
      to patients with erbB-2 positive tumors. Combined predictive value of erbB-2 and
      FA regimen was found to be significant in predicting local relapse in
      multivariate analysis (p = 0.0439). The data suggests that erbB-2 may be
      associated with an improved response to FA regimen and that erbB-2 should be
      included as a potential confounding variable in the analysis of the data from the
      clinical trials for gastric cancer.

PMID- 1355337
TI  - Genetic vulnerability to drug abuse. The D2 dopamine receptor Taq I B1
      restriction fragment length polymorphism appears more frequently in polysubstance
      abusers.
AB  - Alcoholics are more likely than nonalcoholics to display the Taq I A1 restriction
      fragment length polymorphism of the D2 dopamine receptor gene, according to four
      of six studies that examined alcoholics and controls. The current study examines
      whether the association observed in alcoholism might extend to other addictive
      substances by examining D2 dopamine receptor Taq I A and B restriction fragment
      length polymorphisms in polysubstance users and controls free of significant
      substance use. We hypothesized a stronger association for the B1 restriction
      fragment length polymorphism since it lies closer to dopamine receptor protein
      coding and 5' regulatory regions. Heavy polysubstance users and subjects with DSM
      III-R psychoactive substance use diagnoses displayed significantly higher Taq I
      B1 frequencies than control subjects; Taq I A1 results for these comparisons were
      less robust. These results are consistent with a role for a D2 dopamine receptor
      gene variant marked by these restriction fragment length polymorphisms in
      enhanced substance abuse vulnerability.

PMID- 1355338
TI  - Three types of binding by Porphyromonas gingivalis and oral bacteria to
      fibronectin, buccal epithelial cells and erythrocytes.
AB  - This study showed that the interaction of oral bacteria with fibronectin differed
      with the type of organism examined. Significant binding of fibronectin was found
      with Porphyromonas gingivalis non-fimbriated (F-) strain in comparison with the
      fimbriated strain (F+). However, the F+ strain adhered to buccal epithelial cells
      in significantly larger numbers than the F- strain. Fibronectin binding and
      epithelial cell adherence were not associated with haemagglutinating activity.
      These assays clearly define at least three distinct types of binding by oral
      bacteria: to fibronectin, buccal epithelial cells and erythrocytes.

PMID- 1355339
TI  - Enhancement of the effect of low-dose cyclosporin A by sulphasalazine in
      prevention of cardiac allograft rejection in the rat.
AB  - Sulphasalazine (SASP) is an immunomodulatory compound with disease-modifying
      activity in ulcerative colitis and in other autoimmune disorders. SASP was
      previously shown to prolong the survival of heart allografts in rats treated with
      cyclosporin A (CyA) for 9 days after transplantation. We have now evaluated
      whether SASP also exerts a beneficial effect under continuous treatment with CyA,
      when CyA is discontinued after 14 days, or alone if given 10 days prior to
      transplantation. Cardiac grafts were transplanted from PVG donors to Wistar/Kyoto
      recipients using an accessory cervical heart transplantation technique. Rejection
      was defined as the absence of palpable contractions and occurred in the control
      group in a very reproducible manner on day 8 or 9. SASP alone was given orally
      (100 mg/kg body weight) starting 10 days before transplantation and resulted in a
      minor prolongation of graft survival. When SASP was given in addition to oral CyA
      (1 mg/kg or 2 mg/kg from day 0 to rejection) there was a significant prolongation
      in graft survival [from medians of 8 (range 6-11) and 9 (range 8-11) days,
      respectively, to medians of 10 (range 8-15) and 12 (range 11-15) days,
      respectively]. When SASP was given from day 0 to rejection, in addition to a
      schedule of oral CyA (10 mg/kg) for 15 days, there was no prolongation of graft
      survival [median of 30 (range 26-42) days vs median of 32 (26-38) days]. The data
      show that SASP acts as a weak immunosuppressive agent which enhances the effect
      of CyA given at a low dose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355340
TI  - The Ottawa Charter for Health Promotion.

PMID- 1355341
TI  - Self-help groups: their impact and potential.

PMID- 1355342
TI  - Proteinase inhibitors and biological control. IIIrd International Symposium.
      Brdo, Slovenia, June 23-27, 1991.

PMID- 1355343
TI  - Prolyl endopeptidase and dipeptidyl peptidase IV are distantly related members of
      the same family of serine proteases.
AB  - Prolyl endopeptidase and dipeptidyl peptidase IV are serine proteases which
      cleave the peptide bonds at the carboxy group of proline residues. They do not
      show amino acid sequence homology with the known serine enzymes, but a possible
      relationship between them has not yet been examined. We have compared the amino
      acid sequences, and this revealed a distant evolutionary relationship between the
      two enzymes. Conserved segments were found mainly in the C-terminal region which
      also contained the catalytic residues. It is concluded that the C-terminal region
      is a protease domain which is attached to some noncatalytic structures.

PMID- 1355344
TI  - The infectivity of spongiform encephalopathies: does a modified membrane
      hypothesis account for lack of immune response?
AB  - Scrapie, the prototype of a group of diseases which have the unique property of
      being both hereditary and infectious, is also exceptional in that it fails to
      evoke an immune response. Purification of crude scrapie preparations revealed a
      strong association of infectivity with a membrane protein ('PrPsc'); but a
      protein with the same amino acid sequence ('PrPc') was subsequently also found in
      normal mammalian nervous tissue. It is postulated by some investigators that
      'PrPsc' is itself the infectious agent, or the most important part thereof, but
      in papers making that proposal immunological aspects have not been addressed.
      Experimental evidence supporting the hypothesis of a membrane fragment as agent
      has likewise lately not been taken into account. A modified form of the membrane
      hypothesis could account for immunological as well as genetic aspects of these
      diseases.

PMID- 1355346
TI  - Activation pathways and human immunodeficiency virus type 1 replication are not
      altered in CD4+ T cells expressing the nef protein.
AB  - While recent studies in Rhesus monkeys have pointed out the importance of an
      intact nef gene for the development of acquired immunodeficiency syndrome (AIDS),
      no biological function has been so far unambiguously attributed to its product.
      Since Nef has been described to possess GTP-binding properties and to down
      regulate CD4 cell surface expression, we looked for evidences of Nef interfering
      with the transduction of activating signals in human CD4+ T cells. We used a
      murine leukemia retroviral vector to express the HIV-1BRU nef gene in two
      permanent tumoral T-cell lines (CEM and Jurkat) and in two nonimmortalized,
      interleukin-2 (IL2)-dependent, T-cell clones. The single copy recombinant
      provirus integrated in the genome of these cells directed the synthesis of a 27
      kD protein with a half-life greater than 5 h. The levels of expression of cell
      surface molecules involved in T-cell functions (CD4, CD3, CD28, CD29, IL-2
      receptor) were not modified in cell populations expressing Nef. In
      immunocompetent T-cell clones, cell proliferation and lymphokine production in
      response to activating stimuli (IL-2, alloantigens, phorbol esters, or antibodies
      directed against CD2, CD3, CD4, CD28) remained unmodified. Moreover, the presence
      of Nef did not change the kinetics of human immunodeficiency virus (HIV)
      infection.

PMID- 1355345
TI  - [Comparative study of the efficacy and tolerance of cetirizine verses astemizole
      in patients with allergic rhinitis].
AB  - Thirty four patients with allergic rhinitis were included in two randomized
      groups and treated with Cetirizine and Astemizole respectively, 10 mg/day in oral
      administration during 15 days. This study was designed in order to compare the
      efficacy and tolerance of Cetirizine versus Astemizole, with special reference on
      the collateral effects on the central nervous system. Although both drugs showed
      good results. Cetirizine had a statistically significant better outcome in the
      evolution of symptoms, above all at the second day of treatment. Also it showed
      superior results, based on a subjective approach, related to the rapidity, power
      and efficacy of its action.

PMID- 1355347
TI  - Immunopathogenesis of HTLV.

PMID- 1355348
TI  - "A transgenic mouse model for men 2".

PMID- 1355349
TI  - Prediction of doxorubicin resistance in gastrointestinal cancer by P-glycoprotein
      staining.
AB  - Feasibility of immunohistochemical staining of P-glycoprotein for the prediction
      of doxorubicin resistance in gastrointestinal cancers was examined. Among 10
      cancer cell lines which consist of two gastric cancer cell lines and eight colon
      cancer cell lines, seven cell lines were stained positively by the monoclonal
      antibody to P-glycoprotein, C219. In consequence of the evaluation on the effect
      of doxorubicin on these tumour cells by means of succinic dehydrogenase
      inhibition test (SDI test), zero out of seven cell lines stained positively by
      C219 was sensitive to doxorubicin, but two out of three cell lines stained
      negatively were sensitive. Among 23 fresh surgical specimens of gastrointestinal
      cancers which consisted of 15 gastric cancers and eight colon cancers, seven
      tumour tissues were stained positively by C219. All P-glycoprotein positive
      tumours were resistant to doxorubicin. On the other hand, four of 16 P
      glycoprotein tumours were sensitive to doxorubicin. These data indicate that
      positively stained cancer cells by C219 are resistant to doxorubicin.

PMID- 1355350
TI  - Inhibition of gastrin-stimulated growth of gastrointestinal tumour cells by
      octreotide and the gastrin/cholecystokinin receptor antagonists, proglumide and
      lorglumide.
AB  - The rat pancreatic cell line, AR42J possessed high-affinity gastrin and
      somatostatin receptors and its growth was stimulated by physiological gastrin-17
      concentrations between 5 x 10(-11) mol/l and 10(-9) mol/l as measured by
      [75Se]selenomethionine uptake. The somatostatin analogue, octreotide (2 x 10(-7)
      to 2 x 10(-11) mol/l), reduced this stimulated growth. Gastrin-stimulated AR42J
      growth was also inhibited by proglumide (3 x 10(-4) mol/l) and lorglumide (3 x
      10(-5) mol/l) at maximal G17 concentrations of 5 x 10(-11) and 10(-10) mol/l,
      respectively, and the analogues competed with [125I] gastrin-17 (5 x 10(-10)
      mol/l) for binding to gastrin receptors on AR42J (50% inhibitory concentrations,
      less than or equal to 10(-3) mol/l and 4 x 10(-6) mol/l, respectively. Octreotide
      reduced the basal growth of the human gastric cell line, MKN45G, (which is
      associated with intracellular gastrin immunoreactivity) in serum-free medium to
      73% of control at a concentration of 2 x 10(-8) mol/l, which was reversed by
      gastrin-17 (10(-10) mol/l). Lorglumide (3 x 10(-5) mol/l) also reduced the basal
      growth to 30% of control, which was reversed to 78% by 10(-5) mol/l gastrin.
      Proglumide had no effect on the basal growth of MKN45G.

PMID- 1355352
TI  - Virus diseases. Human T-cell lymphotropic virus-1 (HTLV-1).

PMID- 1355351
TI  - Plasma triglyceride and high density lipoprotein cholesterol as predictors of
      ischaemic heart disease in British men. The Caerphilly and Speedwell
      Collaborative Heart Disease Studies.
AB  - OBJECTIVE: To assess the roles of plasma triglyceride and high density
      lipoprotein (HDL) cholesterol concentrations in predicting ischaemic heart
      disease. DESIGN: Two prospective cohort studies with common core protocols.
      SETTING AND PARTICIPANTS: Both cohorts are 100% samples of middle aged men. In
      Caerphilly the 2512 men were living within a defined area. In Speedwell the 2348
      men were registered with local general practitioners. MAIN OUTCOME MEASURES:
      Fasting blood samples were taken at initial examination and plasma lipid
      concentrations were measured. Major ischaemic heart disease events were assessed
      from hospital notes, death certificates, and electrocardiograms. RESULTS: At
      first follow up, after an average of 5.1 years in Caerphilly and 3.2 years in
      Speedwell, 251 major ischaemic heart disease events had occurred. Men with
      triglyceride concentrations in the top 20% of the distribution had a relative
      odds value for ischaemic heart disease of 2.3 (95% confidence interval (95% CI)
      1.3 to 4.1) compared with men in the bottom 20%, after adjusting for both plasma
      total and HDL cholesterol, and non-lipid risk factors. Men in the lowest 20% of
      the distribution of HDL cholesterol concentration had a relative odds value of
      1.7 (95% CI 1.0 to 2.8) compared with the top 20%, after adjustment was made for
      total cholesterol and triglyceride concentrations, and non-lipid risk factors.
      These relations were not caused by beta blockers, which were being taken by 5% of
      the men. CONCLUSIONS: Plasma triglyceride concentration predicts major ischaemic
      events after allowance is made for total and HDL cholesterol concentrations and
      other risk factors. In these populations, triglyceride is a more important
      predictor than total cholesterol concentration.

PMID- 1355353
TI  - Dracunculiasis. Fourth Regional Conference on Dracunculiasis in Africa.

PMID- 1355355
TI  - Second DNA recommendations. 1991 report concerning recommendations of the DNA
      commission of the International Society for Forensic Haemogenetics relating to
      the use of DNA polymorphisms.

PMID- 1355354
TI  - Population genetics and forensic efficiency data of 4 AMPFLP's.
AB  - Family studies were carried out in a population sample from north west Germany
      using 4 amplifiable VNTR polymorphic systems D1S80 (MCT118), ApoB, D17S30 (YNZ22)
      and COL2A1. Separation was carried out in polyacrylamide gels and visualised
      using silver staining. In family studies (n = 30) no evidence of new mutations
      was found. The population study of unrelated individuals (mothers and putative
      fathers) showed that all 4 systems were highly polymorphic and similar to other
      population studies. The combined exclusion chance was calculated to be
      approximately 99% and the combined discrimination index 1.5.10(-4). The Hardy
      Weinberg equilibrium was checked by forming groups of alleles and no significant
      deviations could be found in all systems.

PMID- 1355356
TI  - Functional interaction between the two zinc finger domains of the v-erb A
      oncoprotein.
AB  - The v-erb A oncogene of avian erythroblastosis virus is a mutated and virally
      transduced copy of a host cell gene encoding a thyroid hormone receptor. The
      protein expressed by the v-erb A oncogene binds to DNA and acts as a dominant
      negative inhibitor of both the thyroid hormone receptor and the closely related
      retinoic acid receptor. The v-erb A protein has sustained two amino acid
      alterations within its DNA-binding domain relative to that of c-erb A, one of
      which, at serine 61, is known to be important for v-erb A function in the
      neoplastic cell. We report here that the second alteration, at threonine 78, also
      plays an important, although more indirect, role: alteration of the sequence at
      threonine 78 such that it resembles that of c-erb A can act as an intragenic
      suppressor and can partially restore function to a v-erb A protein rendered
      defective due to a mutation at position 61. Threonine 78 lies within the D-box of
      the v-erb A protein, a region thought to mediate receptor-receptor dimerizations,
      and is not in physical proximity to the serine at position 61. It therefore
      appears that an indirect interaction occurs between these two sites and that this
      interaction is crucial for v-erb A function.

PMID- 1355357
TI  - Increased vomiting among patients treated with neuroleptics.

PMID- 1355358
TI  - The volume of the mediodorsal thalamic nucleus in treated and untreated
      schizophrenics.
AB  - Reductions of 40% in total cell number and 25% in volume of the mediodorsal
      thalamic nucleus were recently reported in an unbiased neurostereological study
      of neuroleptic-treated schizophrenic patients. In order to investigate whether
      these results might be secondary to many years of treatment with neuroleptic
      drugs, eight brains from schizophrenics never treated with neuroleptics and eight
      controls were studied using the unbiased Cavalieri volume estimator. To compare
      left-right differences in this region, twelve neuroleptic-treated schizophrenics
      and eleven control cases were compared. The brains used for the left-right
      comparison study and five of 20 used for comparison of treated and untreated
      brain volumes have been used in an earlier study. The mediodorsal thalamus volume
      was reduced by 31% in untreated schizophrenics and by 22% in neuroleptic-treated
      schizophrenics. No differences were found in mean total volume of the left and
      right mediodorsal thalamus in brains from controls nor from schizophrenics. A
      major difference exists with respect to time of fixation in controls (12 years)
      and untreated schizophrenics (39 years) that makes shrinkage differences a
      possible confounding variable. The results suggest that the consistent reduction
      in number of neurons in the mediodorsal thalamic nucleus are not secondary to
      prolonged treatment with neuroleptic drugs and that asymmetry in this specific
      brain region is not a feature of the schizophrenia-afflicted brain.

PMID- 1355359
TI  - Replication, recombination, and red chilli amidst the Pueblos. Molecular
      mechanisms in DNA replication and recombination. A U.S. Biochemical Corporation
      Keystone symposia, Taos, New Mexico, January 25 to February 1, 1992.

PMID- 1355360
TI  - Cooperative DNA binding of the highly conserved human Hox 2.1 homeodomain gene
      product.
AB  - The human homeobox-containing gene Hox 2.1 (hHox 2.1) and its murine cognate mHox
      2.1 are part of evolutionarily conserved gene clusters, encode an identical
      Antennapedia-type homeodomain, and are expressed in a similar pattern in the
      developing embryo. We have isolated cDNA clones of hHox 2.1 and found that the
      human/murine Hox 2.1 gene structure is strikingly conserved, with only 3 out of
      269 amino acid differences in the entire predicted protein sequence. We show that
      purified hHox 2.1 protein is a sequence-specific DNA binding protein capable of
      binding to a variety of DNA sequences, including multiple sites in the promoter
      of the hHox 2.1 gene. In a footprint titration assay, the apparent affinity of
      the hHox 2.1 protein for a consensus binding site (LP) increases when the site is
      present in tandem copies. Quantitative footprint challenge experiments revealed
      that the in vitro half-life of the protein-DNA complex is less than 30 s for a
      single LP binding site (kd greater than 1.4 min-1), but 126 min for proteins
      bound to two tandem LP binding sites (kd = 5.5 x 10(-3) min-1). A domain distinct
      from the homeodomain is necessary for cooperative DNA binding, because a 61-amino
      acid peptide containing only the Hox 2.1 homeodomain can specifically bind to LP
      sites, but exhibits no cooperativity. A different full-length human homeodomain
      protein, hHox 1.3, was also found to show cooperative DNA binding quantitatively
      similar to hHox 2.1. Therefore, cooperative DNA binding to adjacent sites may be
      a crucial component in the overall affinity of mammalian Antennapedia-type
      homeodomain proteins for their DNA target sites.

PMID- 1355361
TI  - Current issues in thoracic organ transplantation, proceedings. Essen, Germany,
      September 19-21, 1991.

PMID- 1355362
TI  - Receptor systems affecting force of contraction in the human heart and their
      alterations in chronic heart failure.
AB  - Catecholamines acting through beta 1- and beta 2-adrenergic receptors cause
      positive inotropic and chronotropic effects in the human heart. However, recent
      evidence suggests that in the human heart other receptor systems can also affect
      heart rate and contractility. Positive inotropic effects can be mediated by
      receptor systems acting through accumulation of intracellular cyclic adenosine
      monophosphate (cAMP; Gs-protein-coupled receptors such as 5-hydroxytryptamine(5
      HT)4-like, histamine H2, and vasoactive intestinal peptide) or by receptor
      systems acting independently of cAMP, possibly through the phospholipase
      C/diacylglycerol/inositol-1,4,5-trisphophate pathway (such as alpha 1-adrenergic,
      angiotensin II, and endothelin). In the nonfailing human heart, activation of all
      these receptor systems induces only submaximal positive inotropic effects
      compared with those caused by beta-adrenergic receptor stimulation, indicating
      that in humans the cardiac beta-adrenergic receptor/Gs-protein/adenylate cyclase
      pathway is the most powerful mechanism to increase heart rate and contractility.
      However, the human heart contains only a few spare receptors for beta-adrenergic
      receptor-mediated positive inotropic effects and nearly all beta-adrenergic
      receptors are needed to cause maximal inotropic effects. Thus any decrease in the
      number of beta-adrenergic receptors will automatically lead to a reduction in
      functional responsiveness of beta-adrenergic receptors. In chronic heart failure
      the number and responsiveness of cardiac beta-adrenergic receptors are reduced,
      presumably because of the enhanced sympathetic drive to the heart and hence
      endogenous down-regulation by an elevated release of (cardiac-derived)
      norepinephrine, and this loss in cardiac beta-adrenergic receptor function is
      strongly related to the severity of the disease. However, beta 1- and beta 2
      adrenergic receptors are differentially changed in different forms of heart
      failure. In dilated cardiomyopathy and possibly in aortic valve disease the
      number of cardiac beta 1-adrenergic receptors is selectively reduced without
      alteration in the number of beta 2-adrenergic receptors (although beta 2
      adrenergic receptors become somewhat uncoupled). In ischemic cardiomyopathy,
      mitral valve disease, and possibly tetralogy of Fallot, the number of both beta 1
      and beta 2-adrenergic receptors is concomitantly decreased. Because of the lack
      of a substantial receptor reserve, such a decrease in the number of beta
      adrenergic receptors is accompanied by reduced inotropic and chronotropic
      responses to beta-adrenergic receptor stimulation in vitro and in vivo.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1355363
TI  - The amino-terminal peptide of HIV-1 glycoprotein 41 lyses human erythrocytes and
      CD4+ lymphocytes.
AB  - Functional studies assessed the cytolytic activity of the amino terminal peptide
      (FP-I; 23 residues 519-541) of the glycoprotein 41,000 (gp41) of the Human
      Immunodeficiency Virus Type-1 (HIV-1). Synthetically prepared FP-I efficiently
      hemolyzed human red blood cells at 37 degrees C, with 40% lysis at 32 microM.
      Kinetic studies indicated that FP-I induced maximal hemolysis in 30 min, probably
      through tight binding of the peptide with the red cell membrane. The Phe-Leu-Gly
      Phe-Leu-Gly (residues 526-531) motif in FP-I apparently plays a critical role in
      lysis of red cells, since no hemolytic activity was observed for an amino-acid
      substituted FP-I in which the unique Phe-Leu-Gly-Phe-Leu-Gly was converted to Ala
      Leu-Gly-Ala-Leu-Gly. As neither smaller constituent peptides (e.g., residues 519
      524 and residues 526-536) nor a N-terminal flanking peptide (e.g., residues 512
      523) induced red cell hemolysis, the entire 23-residue (519-541) sequence of FP-I
      may be required for hemolytic activity. FP-I was also cytolytic with CD4(+)
      bearing Hut-78 cells, with 40% lysis at approx. 150 microM. These results are
      consistent with an earlier hypothesis that the N-terminal peptide of gp41 may
      partially contribute to the in vivo cytopathic actions of HIV-1 infection
      (Gallaher, W.R. (1987) Cell 50, 327-328).

PMID- 1355364
TI  - The amino-terminal peptide of HIV-1 glycoprotein 41 interacts with human
      erythrocyte membranes: peptide conformation, orientation and aggregation.
AB  - Structural studies assessed interactions between the amino-terminal peptide (FP
      I; 23 residues 519-541) of the glycoprotein 41,000 (gp41) of Human
      Immunodeficiency Virus Type-1 (HIV-1) and human erythrocyte membranes and
      simulated membrane environments. Peptide binding was examined at sub-hemolytic
      (approx. less than 5 microM) and hemolytic (greater than or equal to 5 microM)
      doses (Mobley et al. (1992) Biochem. Biophys. Acta 1139, 251-256), using circular
      dichroism (CD) and Fourier-transform infrared (FTIR) measurements with FP-I, and
      electron spin resonance (ESR) studies employing FP-I spin-labeled at either the
      amino-terminal alanine (FP-II; residue 519) or methionine (FP-III; position 537).
      In the sub-lytic regime, FP-I binds to both erythrocyte lipids and dispersions of
      SDS with high alpha-helicity. Further, ESR spectra of FP-II labeled erythrocyte
      ghosts indicated peptide binding to both lipid and protein. In ghost lipids, FP
      II was monomeric and exhibited low polarity and rapid, anisotropic motion about
      its long molecular axis (i.e., alpha-helical axis), with restricted motion away
      from this axis. The spin-label at the amino-terminal residue (Ala-519) is
      insensitive to the aqueous broadening agent chromium oxalate and buried within
      the hydrophobic core of the membrane; the angle that the alpha-helix (residues
      519-536) makes to the normal of the bilayer plane is either 0 degree or 40
      degrees. Contrarily, ESR spectra of ghost lipids labeled with sub-lytic doses of
      FP-III indicated high mobility and polarity for the reporter group (Met-537) at
      the aqueous-membrane interface, as well as extreme sensitivity to chromium
      oxalate. At lytic FP-I doses, CD and FTIR showed both alpha-helix and beta
      structure for peptide in ghost lipids or detergent, while ESR spectra of high
      loaded FP-II in ghost membranes indicated peptide aggregates. Membrane aggregates
      of FP-I may be involved in hemolysis, and models are suggested for N-terminal
      gp41 peptide participation in HIV-induced fusion and cytolysis.

PMID- 1355365
TI  - A single-base-pair substitution abolishes D-amino-acid oxidase activity in the
      mouse.
AB  - Mutant ddY/DAO- mice lacking D-amino-acid oxidase (DAO) activity were examined
      for the cause of their lack of enzyme activity. Total RNA was extracted from the
      kidney of the ddY/DAO- mice and cDNA was synthesized. After cDNA encoding DAO was
      amplified by the polymerase chain reaction it was cloned into a plasmid and
      sequenced. Comparison of the DAO cDNA sequence with that of normal BALB/c mice
      revealed the presence of a single-base substitution (G----A) which causes a Gly
      181----Arg substitution in the middle of the enzyme molecule. The mutant DAO cDNA
      was inserted into an expression vector and was expressed in transfected COS-1
      cells. The transfected cells synthesized the DAO mutant protein, but they did not
      show DAO activity. In contrast, when cells were transfected with an expression
      vector carrying wild-type DAO cDNA, where the substituted base-pair was replaced
      by a normal base-pair, they showed DAO activity. These results indicate that the
      single base-pair substitution is the cause of the loss of DAO activity in the
      ddY/DAO- mice.

PMID- 1355366
TI  - Transplantation of human neuroblastoma cells, catecholaminergic and non
      catecholaminergic: effects on rotational behavior in Parkinson's rat model.
AB  - Cultured human catecholaminergic and non-catecholaminergic donor cells were used
      in neural transplantation experiments in a rat model of Parkinson's disease.
      Using two different human catecholaminergic neuroblastoma cell lines, one control
      non-catecholaminergic neuroblastoma cell line, and one sham control (tissue
      culture medium), transplants were made into the striatum using a modified
      Ungerstedt hemiparkinsonian rat model. Significant decreases in apomorphine
      induced rotational behavior were produced by two of three catecholaminergic cell
      lines. Grafted cells staining positively for tyrosine hydroxylase (TH) and
      catecholamine fluorescence indicated viable catecholamine activity in the two
      cell lines which produced reductions in rotational behavior. Catecholamine
      fluorescence was not detected in either of the two controls. These data suggest a
      link between catecholamine secretion by transplanted cells and motor improvement
      using a rat rotational behavior model.

PMID- 1355367
TI  - Effects of adrenal medulla and sciatic nerve co-grafts in rats with unilateral
      substantia nigra lesions.
AB  - Major limitations of adrenal medulla transplantation in animal models of
      Parkinson's disease have been the relatively small behavioral effects and the
      poor or inconsistent graft survival. Transplantation of fragments of sural nerve
      in combination with adrenal medulla has been reported to increase the survival of
      chromaffin cells in adrenal medulla grafts in primates. In the present study, the
      possibility was tested that peripheral nerve co-grafts would increase the
      functional effects of adrenal medulla grafts in a 6-hydroxydopamine-lesioned rat
      model. Animals received unilateral substantia nigra lesions, and subsequently
      received intraventricular grafts of adrenal medulla, sciatic nerve, adrenal
      medulla plus sciatic nerve, or sham grafts consisting of medium only. Functional
      effects of the grafts were tested using apomorphine-induced rotational behavior.
      The sciatic nerve co-grafts did not increase the survival of TH-immunoreactive
      chromaffin cells. The co-grafting treatment also did not augment the overall
      effect of adrenal medulla grafts on rotational behavior. In the animals with
      substantial numbers of surviving chromaffin cells, however, the animals with
      sciatic nerve co-grafts showed greater decreases in rotational behavior as
      compared to the animals with adrenal medulla grafts alone, even though the number
      of surviving cells was not increased.

PMID- 1355368
TI  - Inflammatory bowel disease: an uncommon problem in Singapore.
AB  - Fifty patients with inflammatory bowel disease (ulcerative colitis, 40; Crohn's
      disease, seven; indeterminate colitis, three) treated in one gastroenterology
      unit in Singapore over a 10 year period were reviewed. Clinical features were
      similar to those described in Western patients. Of the three main races of
      Singapore it was found that Indians are more susceptible to these diseases than
      Chinese or Malays. A survey of all gastroenterologists in Singapore indicated a
      possible prevalence of 8.6 per 100,000 people for ulcerative colitis and 1.3 per
      100,000 people for Crohn's disease. These prevalence rates are much lower than
      those reported for Western populations.

PMID- 1355369
TI  - GYKI 52466 blocks the increase in extracellular glutamate induced by ischaemia.
AB  - In vivo microdialysis has been used to study the effect of pre- or post-ischaemic
      administration of the non-NMDA antagonist 1-(4-amino-phenyl)-4-methyl-7, 8-methyl
      endioxyl-5H-2,3- benzodiazepine hydrochloride (GYKI 52466), on the increases in
      extracellular glutamate levels induced by 20 minutes of four vessel occlusion in
      rats. In control rats, ischaemia resulted in transient increases in glutamate (4
      fold), aspartate (6 fold) and gamma-aminobutyric acid (GABA) (15 fold) and
      decreases in glutamine (0.5 fold). Intravenous administration of GYKI 52466 (10
      mg kg-1 bolus followed by 10 mg kg-1 h-1 infusion) beginning 20 minutes prior to
      the induction of ischaemia abolished ischaemia-induced glutamate release without
      affecting the increases in aspartate and GABA and the decrease in glutamine.
      Administration of GYKI 52466 immediately post-ischaemia resulted in a more rapid
      return of glutamate levels to basal values.

PMID- 1355370
TI  - Implication of non-NMDA and NMDA receptors in cochlear ischemia.
AB  - We have investigated the hypothesis that the acute ischemic swelling of the
      radial dendrites connected to the inner hair cells (IHCs) is mediated by
      glutamatergic receptors. In control cochleas, after 20 min ischemia all the
      dendrites were dramatically swollen. Conversely, after a perfusion of 50 microM 6
      7-dinitroquinoxaline-2,3-dione (DNQX) before ischemia, most dendrites were
      protected although those contacting the IHCs on their modiolar side frequently
      swelled. After 50 microM of D-2-amino-5-phosphonopentanoate (D-AP5), no dendrite
      protection could be obtained. Finally, after DNQX and D-AP5, no dendrite swelling
      occurred. These results suggest that, in the cochlea, the acute ischemic swelling
      of dendrites primarily occurs via non-NMDA receptors. However, in radial
      dendrites contacting the IHCs on their modiolar side, NMDA receptors may
      contribute to excitotoxicity.

PMID- 1355371
TI  - Characterization of the Ac/Ds behaviour in transgenic tomato plants using plasmid
      rescue.
AB  - We describe the use of plasmid rescue to facilitate studies on the behaviour of
      Ds and Ac elements in transgenic tomato plants. The rescue of Ds elements relies
      on the presence of a plasmid origin of replication and a marker gene selective in
      Escherichia coli within the element. The position within the genome of modified
      Ds elements, rescued both before and after transposition, is assigned to the RFLP
      map of tomato. Alternatively to the rescue of Ds elements equipped with plasmid
      sequences, Ac elements are rescued by virtue of plasmid sequences flanking the
      element. In this way, the consequences of the presence of an (active) Ac element
      on the DNA structure at the original site can be studied in detail. Analysis of a
      library of Ac elements, rescued from the genome of a primary transformant, shows
      that Ac elements are, infrequently, involved in the formation of deletions. In
      one case the deletion refers to a 174 bp genomic DNA sequence immediately
      flanking Ac. In another case, a 1878 bp internal Ac sequence is deleted.

PMID- 1355373
TI  - Detection of human T-cell leukemia/lymphoma virus, type II, in a patient with
      large granular lymphocyte leukemia.
AB  - We studied a patient with large granular lymphocyte (LGL) leukemia for evidence
      of human T-cell leukemia/lymphoma virus (HTLV) infection. Serum from this patient
      was positive for HTLV-I/II antibodies by enzyme-linked immunosorbent assay
      (ELISA) and was confirmed positive in Western blot and radioimmunoprecipitation
      assays. Results of a synthetic peptide-based ELISA showed that the seropositivity
      was caused by HTLV-II and not HTLV-I infection. Analyses of enzymatic
      amplification of DNA from bone marrow sections using the polymerase chain
      reaction (PCR) were positive for HTLV-II specific gag, pol, env, and pX gene
      sequences. Cloning and sequencing of amplified products showed that the HTLV-II
      pol and pX sequences in patient DNA differed from the sequences of 17 other HTLV
      II isolates examined in our laboratory. HTLV infection may have a role in some
      patients in the pathogenesis of LGL leukemia.

PMID- 1355374
TI  - Contact-induced neutrophil activation by platelets in human cell suspensions and
      whole blood.
AB  - Platelet-dependent activation of polymorphonuclear neutrophils (PMNL) was
      investigated with a lumi-aggregometer in heparinized whole blood and platelet
      PMNL suspensions. The lumi-aggregometer allowed us to simultaneously monitor
      increases in impedance or light transmission as consequences of platelet
      aggregation and luminol-enhanced chemiluminescence (CL) as a measure of the
      oxidative burst in PMNL. Aggregation and platelet-PMNL contacts were also checked
      by light and electron microscopy. In whole blood, adenosine diphosphate (ADP) and
      the thromboxane A2 mimetic U 46619 induced the aggregation (increase in
      impedance) and the CL, which were both suppressed by EDTA, arginyl-glycyl
      aspartyl-serine (RGDS) peptide, and the absence of stirring. In contrast, FMLP
      caused only CL that was unaffected by EDTA, RGDS peptide, and nonstirring.
      Similar observations were obtained with mixed suspensions containing washed
      platelets and PMNL at their physiologic concentrations. ADP, U 46619, and
      thrombin induced both aggregation (increase in light transmission) and CL,
      whereas FMLP caused CL but only very weak aggregation. Exogenous fibrinogen
      strongly enhanced the effects of ADP and U 46619. Iloprost, EDTA, RGDS peptide,
      red blood cell (RBC) ghosts, and nonstirring inhibited the effects induced by the
      platelet agonists, but were ineffective on the CL induced by FMLP. Treatment of
      platelets with aspirin did not affect the CL of PMNL induced by platelets.
      Microscopic examination, the requirements of stirring, Ca2+, and fibrinogen, and
      the inhibitory effects of RGDS peptide and RBC ghosts show that stimulated
      platelets activate PMNL in a contact-dependent manner that depends on fibrinogen
      binding. This was confirmed by the immunochemical demonstration of fibrinogen
      (but not of fibronectin) in the contact spaces between activated platelets and
      PMNL. Because supernatants and lysates of resting or thrombin-stimulated
      platelets did not induce the CL of PMNL, soluble agonists did not appear to be
      involved. Nonstimulated washed platelets also caused CL of PMNL that required
      stirring and Ca2+ and was inhibited by RBC ghosts. No CL occurred in unstimulated
      stirred whole blood, suggesting that a preactivation of platelets during the
      preparation may be responsible for the effects of unstimulated washed platelets.
      The results show that platelets provide a strong stimulus for PMNL that requires
      intercellular contact. Fibrinogen exposure on the platelet surface seems to be
      necessary for the activation of PMNL by stimulated platelets.

PMID- 1355372
TI  - The type 1 (EGFR-related) family of growth factor receptors and their ligands.
AB  - This review considers the biology of the type 1 growth factor receptor family
      which is increasingly recognised as important in the control of normal cell
      proliferation and in the pathogenesis of human cancer. The family currently
      comprises three closely related members: the epidermal growth factor (EGF)
      receptor, c-erbB-2 and c-erbB-3, all of which show abnormalities of expression in
      various human tumours. The family of factors related to EGF has also expanded
      recently and now includes transforming growth factor alpha, heparin-binding EGF,
      amphiregulin, cripto and heregulin, as well as several other potential ligands
      for the c-erbB2-2 receptor. The involvement of these receptors and growth factors
      in human cancer has implications for the design of novel forms of therapy for
      cancer, and we review recent advances and future avenues for investigation.

PMID- 1355377
TI  - Neuropharmacology of pain.
AB  - Recent research on the site of action of morphine, its distribution following
      systemic administration and activity in a model of neuropathic pain is reviewed.
      Neuropeptides and pain is discussed in relation to tachykinins and their
      antagonists, cholecystokinin (CCK) and its antagonists and somatostatin.

PMID- 1355375
TI  - Growth inhibition of estrogen independent MXT mouse mammary carcinomas in mice
      treated with an agonist or antagonist of LH-RH, an analog of somatostatin, or a
      combination.
AB  - Female BDF1 mice inoculated with MXT (3.2) estrogen independent mouse mammary
      carcinoma were treated for three weeks with microcapsules of the luteinizing
      hormone-releasing hormone (LH-RH) agonist [D-Trp6]LH-RH, the antagonist SB-75,
      the somatostatin analog RC-160, or combinations. The lack of estrogen dependence
      of the tumor was proved by bilateral surgical ovariectomy, which had no effect.
      In two experiments, treatment with 25 micrograms/day doses of each analog alone
      resulted in a significant inhibition of tumor growth as shown by a 40-53%
      inhibition of tumor volumes, 38-43% decrease in tumor weights, and histological
      signs of tumor regression. However, the combination of SB-75 or [D-Trp6]LH-RH
      with somatostatin analog RC-160 caused greater reduction of tumor volume (68 and
      61%) or tumor weights (59 and 56%), than single analogs, and histologically the
      occurrence of apoptosis and decrease in AgNOR numbers was more pronounced in the
      groups receiving combination therapy. Specific binding sites for [D-Trp6]LH-RH,
      EGF, and IGF-I were demonstrated in the tumor membranes. The binding capacity of
      LH-RH receptors was decreased by treatment with the analogs, the greatest down
      regulation being caused by combination therapy. A significant decrease in EGF
      binding capacity was observed after treatment with the LH-RH analogs, alone or
      especially in combination with somatostatin analog RC-160. The combination of
      these analogs also caused a reduction in IGF-I receptors. The finding that LH-RH
      agonists and antagonists and somatostatin analogs inhibit the growth of estrogen
      independent mammary tumors, and that combinations are more effective than single
      analogs, might be of practical importance in human breast cancer therapy.

PMID- 1355376
TI  - Amino acid substitutions in the Dictyostelium G alpha subunit G alpha 2 produce
      dominant negative phenotypes and inhibit the activation of adenylyl cyclase,
      guanylyl cyclase, and phospholipase C.
AB  - Previous studies have demonstrated that the Dictyostelium G alpha subunit G alpha
      2 is essential for the cAMP-activation of adenylyl cyclase and guanylyl cyclase
      and that g alpha 2 null mutants do not aggregate. In this manuscript, we extend
      the analysis of the function of G alpha 2 in regulating downstream effectors by
      examining the in vivo developmental and physiological phenotypes of both wild
      type and g alpha 2 null cells carrying a series of mutant G alpha 2 subunits
      expressed from the cloned G alpha 2 promoter. Our results show that wild-type
      cells expressing G alpha 2 subunits carrying mutations G40V and Q208L in the
      highly conserved GAGESG (residues 38-43) and GGQRS (residues 206-210) domains,
      which are expected to reduce the intrinsic GTPase activity, are blocked in
      multicellular development. Analysis of down-stream effector pathways essential
      for mediating aggregation indicates that cAMP-mediated activation of guanylyl
      cyclase and phosphatidylinositol-phospholipase C (PI-PLC) is almost completely
      inhibited and that there is a substantial reduction of cAMP-mediated activation
      of adenylyl cyclase. Moreover, neither mutant G alpha 2 subunit can complement g
      alpha 2 null mutants. Expression of G alpha 2(G43V) and G alpha 2(G207V) have
      little or no effect on the effector pathways and can partially complement g alpha
      2 null cells. Our results suggest a model in which the dominant negative
      phenotypes resulting from the expression of G alpha 2(G40V) and G alpha 2(Q208L)
      are due to a constitutive adaptation of the effectors through a G alpha 2
      mediated pathway. Analysis of PI-PLC in g alpha 2 null mutants and in cell lines
      expressing mutant G alpha 2 proteins also strongly suggests that G alpha 2 is the
      G alpha subunit that directly activates PI-PLC during aggregation. Moreover,
      overexpression of wild-type G alpha 2 results in the ability to precociously
      activate guanylyl cyclase by cAMP in vegetative cells, suggesting that G alpha 2
      may be rate limiting in the developmental regulation of guanylyl cyclase
      activation. In agreement with previous results, the activation of adenylyl
      cyclase, while requiring G alpha 2 function in vivo, does not appear to be
      directly carried out by the G alpha 2 subunit. Our data are consistent with
      adenylyl cyclase being directly activated by either another G alpha subunit or by
      beta gamma subunits released on activation of the G protein containing G alpha 2.

PMID- 1355378
TI  - Effects of omeprazole on the number of immunoreactive gastrin- and somatostatin
      cells in the rat gastric mucosa.
AB  - The effects of omeprazole--an inhibitor of gastric acid secretion--on gastrin (G)
      and somatostatin (D)-cell density in the gastric antral mucosa epithelium in
      rats were examined, following a 5-day treatment. It was found that omeprazole
      increased the density of G-cells, whereas it decreased the density of D-cells.
      That effect was probably independent of hypergastrinaemia, since it could not be
      blocked by a simultaneous treatment with proglumide--a gastrin receptor blocker.
      It is concluded that the observed phenomenon is a direct result of a lower
      gastric acidity, as a consequence of omeprazole treatment.

PMID- 1355379
TI  - [Interferon-gamma suppresses expression of the HER-2 oncogene in ovarian cancer
      cells].
AB  - The overexpression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian and
      mammary carcinoma is an important indicator for a bad prognosis. In this study we
      demonstrate that in 7 out of 8 ovarian carcinoma cell lines there is an
      interferon-gamma-mediated reduction in HER-2 specific protein, and this effect
      was found to correlate with the antiproliferative action. It is interesting to
      note that there is no relationship between the absolute amount of HER-2 protein
      expressed and the sensitivity of the ovarian carcinoma cells for an
      antiproliferative activity of interferon-gamma. Other chemotherapeutic agents did
      not affect HER-2 expression although they inhibited the proliferation. The
      oncogene expression was lowered only in the ovarian carcinoma cell lines and not
      in 3 interferon-gamma sensitive human breast cancer cell lines. Expression of the
      oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation
      might represent a mechanism by which interferon-gamma inhibits cell
      proliferation.

PMID- 1355380
TI  - Treatment of hypertension in older adults.

PMID- 1355381
TI  - Missed neuroleptic malignant syndrome.

PMID- 1355382
TI  - Preschool screening for cryptorchidism.

PMID- 1355383
TI  - A mathematical model of the P-glycoprotein pump as a mediator of multidrug
      resistance.
AB  - Cells displaying the classic multidrug resistant (MDR) phenotype possess a
      transmembrane protein (p170 or P-glycoprotein) which can actively extrude
      cytotoxic agents from the cytoplasm. A mathematical model of this drug efflux
      pump has been developed. Outward transport is modeled as a facilitated diffusion
      process. Since energy-dependent efflux of cytotoxic agents requires that ATP also
      bind to p170, the model includes a dynamic calculation for efflux rate which
      considers Michaelis-Menten kinetics for both the substrate agent and ATP. The
      final system consists of one partial differential equation (PDE) for the
      facilitated diffusion of substrate agents out of the cell, a 2 x 2 ordinary
      differential equation (ODE) system for the dynamic calculation of the ATP-ADP
      pool, and a dynamic algebraic calculation of the efflux rate given substrate
      levels at the interior cell membrane interface and ATP levels in the cell. A
      stability analysis of the ATP-ADP pool distribution and a simplistic closed form
      solution of the linearized PDE are included. Numerical simulations are also
      provided.

PMID- 1355385
TI  - Microinjection of L-glutamate into the nucleus tractus solitarii increases
      arterial pressure in conscious rats.
AB  - Microinjection of L-glutamate into the nucleus tractus solitarii (NTS) of
      anesthetized rats produces a fall in mean arterial pressure (MAP) similar to that
      observed during activation of baroreceptor afferents. In the present study we
      examined the effect of bilateral microinjections of L-glutamate through
      chronically implanted cannulae in the NTS of conscious freely moving rats. Group
      I (n = 6) was studied under conscious conditions and 24 h later the rats were
      anesthetized with urethane and the effects of L-glutamate re-examined. In
      conscious rats, L-glutamate (30 pmol to 5 nmol/100 nl) produced dose-dependent
      increases in MAP (+37 +/- 7 mmHg, 5 nmol), whereas under urethane anesthesia
      falls in MAP were observed (-11 +/- 3 mmHg, 5 nmol). Group II (n = 7) was studied
      under conscious conditions and 1 h later the rats were anesthetized with
      chloralose and the effects of L-glutamate re-examined. In this group of conscious
      rats L-glutamate (300 pmol to 5 nmol/100 nl) also produced dose-dependent
      increases in MAP (+37 +/- 5 mmHg, 5 nmol), whereas under chloralose anesthesia a
      dose-dependent depressor response was observed (-33 +/- 6 mmHg, 5 nmol). Saline
      microinjections into the NTS of conscious and anesthetized rats produced
      negligible effects. These data demonstrate that microinjection of L-glutamate
      into the NTS of rats produces a pressor response in conscious animals in contrast
      to depressor responses in animals anesthetized with chloralose or
      urethane.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355384
TI  - Effect of methylxanthine derivatives on T cell activation.
AB  - In a Phase I-II trial examining the effect of prophylactic administration of
      pentoxifylline (PTX) on bone marrow transplant-associated morbidity, there was an
      apparent reduction in the incidence and severity of acute graft-versus-host
      disease. To determine if PTX might be directly immunosuppressive, its effects on
      T cell activation and proliferation were examined. PTX and several cogeners were
      found to directly suppress T cell proliferation in response to
      phytohemagglutinin, to allogeneic cells in a mixed leukocyte reaction, and to
      cross-linking the CD3 complex. The effects were dose-related and associated with
      suppression of secretion of tumor necrosis factor-alpha (TNF alpha). However, the
      inhibition of proliferation was not solely due to this effect since adding excess
      recombinant TNF alpha did not restore the proliferative response. These data
      suggest that PTX may be clinically useful in suppressing allogeneic reactions in
      bone marrow transplantation.

PMID- 1355386
TI  - The learning capacity of high or low performance rats is related to the
      hippocampus NMDA receptors.
AB  - The hippocampal synaptic plasticity of rats with an inborn high (HP) or low (LP)
      learning capacity to perform in a shuttle box is closely related to their
      percentage of conditioned responses (Crs). HP rats show less sensitivity to the
      blocking effect of 2-aminophosphonopentanoic acid (AP5) on the generation of long
      term potentiation (LTP) than do LP rats. Results described in the present report
      are indicative of an increased density of N-methyl-D-aspartate (NMDA) receptors
      in HP rats compared to control and LP rats. We postulate that the differential
      pharmacological sensitivity of LTP in these rats is a reflection of this
      biochemical difference. Also, from these results we suggest that the learning
      capacity may be related to the density of glutamate NMDA receptors of HP, LP and
      control rats.

PMID- 1355387
TI  - Stimulation of alpha 2-adrenergic receptors in nucleus tractus solitarius is
      required for the baroreceptor reflex.
AB  - Bilateral injection into the nucleus tractus solitarius (NTS) of the alpha 2
      adrenergic receptor antagonist yohimbine produced a dose-related (10-500 pmol)
      increase in arterial pressure, with a maximal response of approximately 60 mm Hg.
      Idazoxan, also an alpha 2-adrenergic receptor antagonist, produced a similar
      response although idazoxan was less potent than yohimbine. The pressor response
      elicited by these drugs was attenuated by stimulation of adrenergic receptors in
      the NTS by local administration of either clonidine or tyramine. Doses of
      yohimbine (200 pmol) or idazoxan (5 nmol) that maximally increased arterial
      pressure also completely inhibited the depressor and bradycardic responses to
      electrical stimulation of the aortic depressor nerve. These results indicate that
      tonic stimulation of alpha 2-adrenergic receptors in the NTS is required for
      baroreceptor reflex function.

PMID- 1355388
TI  - Glutamate release and presynaptic action of AP4 during inspiratory drive to
      phrenic motoneurons.
AB  - High-performance liquid chromatography (HPLC) was used to detect the presence of
      excitatory amino acids released from bulbospinal axon terminals projecting to
      cervical spinal respiratory motoneurons during transmission of inspiratory drive
      in an in vitro neonatal rat brainstem-spinal cord preparation. Measurements were
      then repeated under paradigms where transmitter release was decreased by either
      depression of bulbospinal respiratory drive, or by adding DL-2-amino-4
      phosphonobutyrate (AP4) to the solution bathing the spinal cord. The amounts of
      glutamate, but not aspartate, released decreased significantly with depressed
      brainstem inspiratory drive or the activation of AP4-sensitive receptors within
      the cervical (C) spinal cord.

PMID- 1355389
TI  - Acetylcholine release in the hippocampus: regulation by monoaminergic afferents
      as assessed by in vivo microdialysis.
AB  - The role of monoamines in the functional regulation of the septo-hippocampal
      cholinergic system was studied using in vivo microdialysis of acetylcholine (ACh)
      release in the hippocampus of awake unrestrained rats. Systemic administration of
      the dopamine receptor agonist apomorphine (2.0 mg/kg) resulted in a 170% increase
      in hippocampal ACh overflow. Similarly the catecholamine-releasing agent
      amphetamine (2.5 mg/kg) produced a 400% increase in ACh overflow. The effect
      induced by amphetamine, but not that of apomorphine, was blocked in animals
      pretreated with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine
      (AMPT). The effect of amphetamine on ACh release was reduced by 75% after a 6
      hydroxydopamine (6-OHDA) lesion of the ventral tegmental area (VTA) but was not
      affected by 6-OHDA lesions of the noradrenergic dorsal and ventral bundles.
      However, baseline ACh overflow was increased by 130% by the dorsal and ventral
      bundle lesions. The serotonin-releasing agent p-chloroamphetamine (2.5 mg/kg)
      produced a 160% increase in hippocampal ACh release, and this effect was enhanced
      after a 5,7-dihydroxytryptamine (5,7-DHT) lesion of the serotonin projection
      system. The results show that surgical or pharmacological manipulations of the
      ascending brainstem monoaminergic systems, which innervate wide areas of the
      forebrain, including the septum and the hippocampal formation, have pronounced
      effects on septo-hippocampal cholinergic activity. Thus, the present data provide
      support for the view that information regarding behavioral state and arousal is
      conveyed to the septo-hippocampal system via ascending monoaminergic systems.

PMID- 1355390
TI  - Age-related alterations of NMDA-receptor properties in the mouse forebrain:
      partial restoration by chronic phosphatidylserine treatment.
AB  - The effect of aging on the properties of N-methyl-D-aspartate (NMDA) receptors in
      the forebrain of female NMRI mice was investigated using the antagonist [3H]MK
      801 as radioligand. Compared to young (3 months) mice, aged (20 months) mice
      showed changes of the properties of the NMDA receptor at three different levels:
      (1) the density was reduced by about 35%; (2) the efficacy of L-glutamate and
      glycine for stimulating specific [3H]MK-801 binding was enhanced, probably
      because more NMDA receptor-associated ion channels are closed under baseline
      conditions in the aged brain; (3) the affinity of L-glutamate and glycine to its
      binding sites at the NMDA receptor complex was also enhanced. Chronic treatment
      of aged mice with phosphatidylserine (20 mg/kg, i.p., once daily) for three weeks
      completely normalized enhanced efficacy and affinity of L-glutamate and glycine
      and elevated NMDA receptor density by approximately 25%. These findings are
      consistent with the assumptions that deficits of the NMDA receptor are one of the
      mechanisms of age-related cognitive impairment and that the beneficial effects of
      phosphatidylserine treatment on cognitive deficits of aged individuals might be
      partially due to the effects of this drug on age-related NMDA receptor deficits.

PMID- 1355391
TI  - The effect of morphine tolerance dependence and abstinence on immunoreactive
      dynorphin (1-13) levels in discrete brain regions, spinal cord, pituitary gland
      and peripheral tissues of the rat.
AB  - The effect of morphine tolerance dependence and protracted abstinence on the
      levels of dynorphin (1-13) in discrete brain regions, spinal cord, pituitary
      gland and peripheral tissues was determined in male Sprague-Dawley rats. Of all
      the tissues examined, the highest level of dynorphin (1-13) was found to be in
      the pituitary gland. Among the brain regions and spinal cord examined, the levels
      of dynorphin (1-13) in descending order were: hypothalamus, spinal cord,
      midbrain, pons and medulla, hippocampus, cortex, amygdala and striatum. The
      descending order for the levels of dynorphin (1-13) in peripheral tissues was:
      adrenals, heart and kidneys. In morphine tolerant rats, the levels of dynorphin
      (1-13) increased in amygdala but were decreased in pons and medulla. In morphine
      abstinent rats, the levels of dynorphin (1-13) were increased in amygdala,
      hypothalamus and hippocampus. The levels of dynorphin (1-13) were increased in
      pituitary but decreased in spinal cord and remained so even during protracted
      abstinence. The levels of dynorphin (1-13) in the peripheral tissues of morphine
      tolerant rats were unaffected. However, in the heart and kidneys of morphine
      abstinent rats, the levels of dynorphin (1-13) were increased significantly. It
      is concluded that both morphine tolerance and abstinence modify the levels of
      dynorphin (1-13) in pituitary, central and peripheral tissues. Morphine
      abstinence differed from non-abstinence process in that there were additional
      changes (increases) in the levels of dynorphin (1-13) in brain regions
      (hypothalamus and hippocampus) and peripheral tissues (heart and kidneys) and may
      contribute to the symptoms of the morphine abstinence syndrome.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1355392
TI  - Tyrosine-hydroxylase-containing neurons in the primate basal forebrain
      magnocellular complex.
AB  - Immunocytochemistry and in situ hybridization for tyrosine hydroxylase (TH) were
      used to study the distribution of putative catecholaminergic neurons in the basal
      forebrain magnocellular complex (BFMC) of monkeys and humans. Magnocellular TH
      expressing neurons in the primate BFMC are distributed along a rostrocaudal
      gradient, with the largest proportion of these cells located in the medial septal
      nucleus and nucleus of the diagonal band of Broca; smaller TH-containing neurons
      generally follow the same distribution. These findings suggest that, within
      rostromedial segments of the BFMC, there is a distinct subpopulation of neurons
      that express catecholamine-synthesizing enzymes. Further research is necessary to
      establish whether these neurons utilize one or more catecholamines as
      neurotransmitters.

PMID- 1355393
TI  - Comparison of the expression, transcription and genomic organization of D2
      dopamine receptors in outbred and inbred strains of rat.
AB  - Three outbred (Sprague-Dawley, Wistar and Long-Evans) and five inbred (Brown
      Norway, Buffalo, DA, Fisher and Lewis) strains of rat were used to investigate
      the extent of genetic variation in the expression and organization of the rat D2
      receptor locus. Radioligand binding studies were performed using 125I
      iodobenzamide ([125I]IBZM), a high-affinity antagonist for D2 dopamine receptors,
      to determine the extent of variation in the expression of D2 receptors in these
      strains of rat. A comparison of the affinities (Kd = 0.26-0.38 nM) and densities
      (450-580 fmol/mg of protein) of binding sites for [125I]IBZM in the striatum of
      the eight strains of rat did not reveal statistically significant differences.
      Solution hybridization using 32P-labeled riboprobes complementary to the coding
      region of the third intracellular loop of the D2 receptor was used to investigate
      the extent of variation in transcription of the long (D2L) and short (D2S)
      isoforms of D2 receptor mRNA in rat striatal tissue. The level of expression of
      these two mRNA isoforms was found to be invariant in the strains of rats that
      were examined. The genomic organization of the D2 receptor locus for each strain
      of rat was compared using Southern blot hybridization. Southern blots were
      hybridized with a DNA probe that codes for the D2L receptor isoform. Restriction
      fragment lengths were conserved between each rat strain for genomic DNA digested
      with BamHI, EcoRI, HindIII, PstI and TaqI. Restriction fragment length
      polymorphisms (RFLPs) were identified when genomic DNA was digested with XbaI or
      MspI. The XbaI polymorphism was mapped to within 2 kb of the exon coding for the
      third intracellular loop of the D2 receptor. Both RFLPs differentiated Sprague
      Dawley and Brown-Norway rats from Wistar, Long-Evans, Buffalo, DA, Lewis and
      Fisher rats. The RFLPs for the rat D2 receptor locus provide genetic markers that
      can be used with classic genetic studies to determine whether strain differences
      in behavior and/or in the response to pharmacologic intervention are determined
      by genetic elements linked to the D2 receptor locus.

PMID- 1355394
TI  - Dopamine and melatonin interactions in the intact chicken eye.
      Electrooculographic and biochemical study.
AB  - Electrophysiological and biochemical techniques were used to investigate the
      interactions between dopamine (DA) and melatonin (MEL) in the intact chicken eye.
      Endogenous DA depletion induced by intraocular administration of alpha-methyl
      para-tyrosine (alpha-MPT), a selective tyrosine hydroxylase inhibitor, decreases
      the transepithelial potential (TEP) of the retinal pigment epithelium and reduces
      the light peak (LP) recorded by an indirect electro-oculographic (EOG) method. An
      intraocular injection of MEL also reduces the TEP but does not reduce the LP.
      Retinal MEL is increased after endogenous DA depletion and a tight inverse
      correlation between DA and MEL contents was found. The present data, together
      with other findings support the hypothesis (1) that in the intact chicken eye, DA
      and MEL play respectively a role of light and dark signals on the TEP, and (2)
      that a balance between these two neurohormones may be responsible for the
      regulation of RPE events which are dependent on light-dark conditions.

PMID- 1355396
TI  - Neuromuscular blocking agents of intermediate duration in children.

PMID- 1355395
TI  - Analgesia from the periaqueductal gray in the developing rat: focal injections of
      morphine or glutamate and effects of intrathecal injection of methysergide or
      phentolamine.
AB  - The aim of these experiments was to examine the changes in antinociception
      elicited by morphine or glutamate stimulation of the periaqueductal gray of the
      midbrain (PAG) during the postnatal development of the rat. Pups, aged 3, 10, and
      14 days, were implanted with cannulas aimed at either the dorsal or the ventral
      aspect of the PAG, and glutamate (vehicle, 60 mM or 180 mM) or morphine (vehicle,
      2 micrograms or 6 micrograms) was microinjected into one of those two sites. Pups
      were tested for analgesia against noxious thermal and mechanical stimuli.
      Morphine produced analgesia at 3 and 10 days of age only when administered to the
      ventral part of the PAG and the thermal noxious stimulus was tested. Conversely,
      analgesia induced by glutamate was seen at 3 and 10 days of age only when
      glutamate was given to the dorsal aspect of the PAG and the mechanical stimulus
      was used. In 14-day-old pups, both drugs produced analgesia against both types of
      noxious stimuli regardless of their site of administration within the PAG.
      Systemically administered naloxone attenuated the analgesic effects of both drugs
      when they were administered to the ventral PAG, but did not consistently
      attenuate the analgesic effect of either compound given to the dorsal aspect of
      the PAG. When either morphine or glutamate was injected into the ventral PAG,
      intrathecal injections of methysergide attenuated analgesia against the thermal
      stimulus to a significantly greater degree than the mechanical stimulus and
      intraspinal injection of phentolamine attenuated analgesia against the mechanical
      stimulus more potently. When glutamate was given to the dorsal PAG, analgesia
      against both stimulus types was significantly attenuated. These results indicate
      that the morphine- and glutamate-induced analgesia mediated by the PAG are
      developmentally differentiated. These ontogenetic differences most likely reflect
      differences in the mechanism of action by which these drugs produce analgesia
      when administered to the PAG, as well as neuroanatomical differences within the
      dorsal and the ventral regions of the PAG.

PMID- 1355397
TI  - Demonstration of proteases in basal cell carcinomas. A histochemical study using
      amino acid-4-methoxy-2-naphthylamides as chromogenic substrates.
AB  - BACKGROUND: Proteases are reported to play an essential part in the
      proliferative, invasive, and metastasizing behavior of malignant tumors. The aim
      of the current study was to determine the activity and localization of proteases
      in basal cell carcinomas (BCC) histochemically. METHODS: Various proteases were
      identified histochemically in frozen sections of BCC. The following amino acid-4
      methoxy-2-naphthylamides (MNA) were used as chromogenic substrates:alanine-MNA
      for the detection of aminopeptidase M (APM), glycyl-proline-MNA for dipeptidyl
      peptidase IV (DPP IV), lysyl-proline-MNA and lysyl-alanine-MNA for dipeptidyl
      peptidase II (DPP II), glycyl-arginine-MNA for dipeptidyl peptidase I (DPP I),
      and carbobenzoxy (CBZ)-arginyl-arginine-MNA for cathepsin B. RESULTS: APM
      activity was high in the peritumorous connective tissue, whereas the tumor
      epithelium and epidermis had negative results. DPP IV showed a highly positive
      reaction in both tumor epithelium and surrounding connective tissue. Cathepsin B
      and DPP I reacted strongly in the tumor epithelium but not in the peritumorous
      connective tissue. CONCLUSIONS: The marked activity of APM, DPP IV, DPP I, and
      cathepsin B may be related to the proliferation and invasive growth of BCC. The
      distribution of the activity of APM and DPP IV indicates dynamic interactions
      between the tumor epithelium and the adjacent connective tissue in the neoplastic
      process.

PMID- 1355398
TI  - The expression of proliferating cell nuclear antigen in paraffin sections of
      peripheral, node-negative non-small cell lung cancer.
AB  - Cell proliferation of 40 peripheral, node-negative non-small cell lung cancers
      (NSCLC) treated with surgery alone was investigated by immunohistochemical
      analysis with the monoclonal antibody (MoAb) PC10, which recognizes a
      proliferating cell nuclear antigen (PCNA) in formalin-fixed and paraffin-embedded
      material. Results were correlated with DNA ploidy and S-phase fraction (SPF)
      analyzed by DNA flow cytometric study. Mitotic count (MC) was analyzed by light
      microscopic study and histopathologic features. PCNA immunoreactivity was seen in
      all samples and confined to the nuclei of cancer, but not to the surrounding,
      tumor-negative cells; its frequency ranged from 0-70% (median, 15%), and tumors
      expressed either a low (0-25%, n = 25) or intermediate (26-75%, n = 15)
      proliferative activity. There was no relationship between PCNA immunoreactivity
      and tumor stage or among size, histologic type, and mitotic count (MC). Tumors
      with intratumoral blood vessel invasion (BVI) showed a significantly higher (P
      less than 0.005) PCNA immunoreactivity than BVI-negative tumors. PCNA scores were
      significantly higher (P less than 0.005) in DNA aneuploid (n = 22) than in DNA
      diploid (n = 18) tumors and correlated significantly with the SPF of DNA
      aneuploid tumors (r = 0.825, P less than 0.0001), but not with diploid tumors (r
      = 0.002, P = 0.9). Intermediate proliferating tumors had a significantly higher
      (P less than 0.01) MC than their counterparts. In univariate analysis,
      significant predictors of survival were tumor classification (T1 versus T2),
      tumor size (less than or equal to 2.6 cm versus more than 2.6 cm), BVI (BVI
      negative versus BVI-positive), MC (less than or equal to 8 versus more than 8),
      and PCNA immunoreactivity (low versus intermediate). DNA ploidy and SPF did not
      influence survival significantly. Only PCNA immunoreactivity retained its
      independent level of significance (P = 0.02) by multivariate analysis. It was
      concluded that PCNA immunostaining is a simple and clinically useful method for
      estimating cell proliferation in formalin-fixed, paraffin-embedded tissue of
      resected peripheral, node-negative NSCLC.

PMID- 1355400
TI  - Proceedings of the National Conference on Integration of Molecular Genetics into
      Cancer Management. Miami, Florida, April 10-12, 1991.

PMID- 1355399
TI  - Prognostic significance of the PC10 index as a prospective assay for cervical
      cancer treated with radiation therapy alone.
AB  - The monoclonal antibody PC10 recognizes proliferating cell nuclear antigen (PCNA)
      in conventionally fixed and processed histologic materials. Formaldehyde-fixed
      and paraffin-embedded specimens taken from 194 patients with Stage III squamous
      cell carcinoma of the cervix treated with radiation therapy alone were
      investigated for PC10 positivity using immunohistochemical methods. A few
      squamous epithelial cells in the basal layer and the deepest zone of the prickle
      cell layer were positive for PC10. Cancer cells also were positive for PC10,
      showing a diffuse or granular nuclear staining pattern. The multiple logistic
      regression model analysis and the Kaplan-Meier method indicate that a strong
      correlation exists between the PC10 index and prognosis (P less than 0.001).
      Thus, the PC10 index may be a predictive indicator for the prognosis of patients
      with squamous cell carcinoma of the cervix treated with radiation therapy alone.

PMID- 1355401
TI  - Gene structure, function, and abnormalities.

PMID- 1355402
TI  - Genetic markers as prognostic indicators in breast cancer.
AB  - BACKGROUND: Identifying markers that have the potential to predict tumor behavior
      is important in breast cancer because of the variability in clinical disease
      progression. Genetic alterations in tumors may appear as changes in total DNA
      content, individual chromosomes, single genes, or gene expression. Alteration in
      DNA content is an imprecise but accessible measurement of the genome. Diploid
      tumors have been associated with a better clinical outcome, and increased ploidy
      correlates with other indicators of poor prognosis. Concurrent analysis of DNA
      content with markers of genetic expression is feasible (e.g., myc oncogene) and
      may increase its prognostic power. Chromosomal studies could provide a more
      precise tool for localizing genetic damage, but there is little cytogenetic
      information about primary breast cancers, no convincing evidence has emerged to
      target locations in the karyotype that appear specifically altered, and many
      primary and cultured breast cancers contain cells that appear chromosomally
      normal. Attempts to define molecular markers have used probes of different
      chromosomal sites, some chosen because of logical associations with hormonal
      activity, known oncogenes, or tumor-suppressor genes, and some by chance.
      Currently, to the authors' knowledge, none has shown uniform changes by mutation,
      loss, or overexpression in all breast cancers, although a remarkable number of
      loci are altered to some extent. These lesions must be associated with particular
      disease subsets or, retrospectively, with differential survival if they are to
      have prognostic value. METHODS: The authors examined several loci (ERBB2, INT2,
      MUC1) for gene amplification or loss of heterozygosity by Southern blotting and
      for gene expression by immunohistochemistry in breast tumors from patient groups
      selected by survival. RESULTS AND CONCLUSIONS: A retrospective series showed gene
      amplification at the erbB2 locus in 22% of rapidly recurrent (RR) tumors and 13%
      of tumors from long-term tumor-free survivors (LTS), but the difference was not
      statistically significant (P = 0.18). The erbB2 product was displayed
      histochemically with equal frequency between those with RR tumors and LTS
      patients. Moreover, the correlation was poor between different analytic measures
      on the same tumors. This result was tested using a prospective study of erbB2 to
      correlate DNA analysis with western blot findings and frozen and fixed
      histochemical results. Another oncogene, int2, showed significant correlation
      between amplification and recurrence; 16% of RR tumors showing genetic
      amplification (P = 0.02). Loci on other chromosomes, 1 (muc1) and 17 (cmm86),
      also are being investigated in groups selected for differences in survival.

PMID- 1355403
TI  - Prognosis and treatment decisions in patients with breast cancer without axillary
      node involvement.
AB  - BACKGROUND: Every month, treatment decisions must be made for more than 6000
      patients with breast cancer without axillary node involvement in the United
      States. Approximately 70% of these patients will survive more than 10 years after
      surgery and/or radiation treatment without additional systemic adjuvant therapy.
      If we had good methods to identify patients who are destined to have a recurrence
      of their disease, only those patients should receive adjuvant therapy. METHODS:
      The authors reviewed the literature supporting the use of currently available
      prognostic factors for patients with node-negative breast cancer, and formulated
      a framework on which prognostic factor information can be based to help make
      these treatment decisions. RESULTS: The steps involved in making treatment
      decisions are: use prognostic factors to determine the recurrence probability;
      calculate the expected treatment benefit; and weigh the expected benefits against
      the potential risks. CONCLUSIONS: Prognostic factors can be used to help make
      treatment decisions for patients with breast cancer without axillary node
      involvement. However, the final treatment decision must take into account all
      aspects of the patient and her disease, and the physician must help the patient
      evaluate her prognostic factors, arrive at an understanding of her particular
      risk of recurrence, and weigh the potential benefits and risks of adjuvant
      therapy.

PMID- 1355404
TI  - Genetic aspects of multidrug resistance.
AB  - Mammalian cells exposed to a single cytotoxic natural product drug, such as
      vincristine or dactinomycin, can develop resistance to the selective agent and
      cross-resistance to a broad spectrum of structurally and functionally distinct
      antibiotics and alkaloids. This phenomenon, termed multidrug resistance (MDR),
      has been widely studied experimentally. The most consistent feature of cells with
      high-level MDR is amplification and overexpression of genes encoding an integral
      plasma membrane protein known as P-glycoprotein. The MDR genes belong to a small
      family (two members in humans and three members in mouse and Chinese hamster).
      Based on several lines of evidence, P-glycoprotein is thought to act as an
      adenosine triphosphate-dependent efflux pump that decreases accumulation of drugs
      and increases resistance to their effects. The normal function of P-glycoprotein,
      apart from its role in MDR, is not known. Proposed roles in detoxification and
      steroid transport systems are speculative but suggest that the membrane protein
      may have distinct functions in normal tissues and in tumor cells with acquired
      MDR. Although possible endogenous substrates for P-glycoprotein have not been
      identified, insight into normal function may be gained from tissue distribution
      studies. For example, studies using molecular probes to P-glycoprotein messenger
      RNA and monoclonal antibodies to different epitopes of the molecule have shown
      that P-glycoprotein is expressed at high levels in the more differentiated or
      specialized cells of the colon or kidney. Amplification of MDR genes in vivo has
      not been observed. Whether intrinsic or acquired MDR plays a causal and
      potentially modifiable role in clinical nonresponsiveness to cancer
      chemotherapeutic agents is a topic of current interest. Prospective studies and
      serial determinations during the course of disease are needed to clarify the
      importance of this membrane protein in clinical drug resistance.

PMID- 1355405
TI  - Oral cancer progression and c-erbB-2/neu proto-oncogene expression.
AB  - Monoclonal antibody PAb3 to c-erbB-2/neu protein was utilized in the
      immunoperoxidase staining of 86 human specimens from oral mucosa. These tissue
      specimens represented a spectrum from 7 normal to 9 simple hyperplasia, 15 mild
      dysplasia, 14 moderate dysplasia, 20 severe dysplasia and 21 squamous cell
      carcinoma. Our study indicated that as the cells acquire a more malignant
      phenotype, there was a progressive increase in neu expression. It also suggested
      that neu may be involved in the development of oral cancers and that its
      evaluation in the early stages may assist in the diagnosis and management of oral
      cancers.

PMID- 1355406
TI  - Increase in gamma-glutamylcysteine synthetase activity and steady-state messenger
      RNA levels in melphalan-resistant DU-145 human prostate carcinoma cells
      expressing elevated glutathione levels.
AB  - The biochemical and molecular basis for the elevation of glutathione (GSH) levels
      commonly detected in many drug-resistant cells has not been elucidated. In a
      series of L-phenylalanine mustard-resistant human prostate carcinoma cell lines
      (DU-145), resistance was associated with elevated GSH levels, increased activity
      of gamma-glutamylcysteine synthetase (GCS), the rate-limiting enzyme in GSH
      biosynthesis, and a marked increase in the steady-state levels of GCS-specific
      transcripts (4.0 and 3.2 kilobases). Loss of the resistant phenotype was
      accompanied by a reduction in GSH and a return of GCS activity and transcript
      levels to values comparable to those detected in the drug-sensitive parent cells.
      These data strongly implicate up-regulation of GCS activity as an important
      mechanism in the evolution of drug resistance associated with increased levels of
      intracellular GSH. The results further suggest that the ability to synthesize GSH
      may be more indicative of resistance than steady-state GSH levels per se.

PMID- 1355407
TI  - Weak antiparkinsonian activity of the D1 agonist C-APB (SKF 82958) and lack of
      synergism with a D2 agonist in primates.
AB  - The role of D1 receptors in motor control is poorly understood. In parkinsonian
      squirrel monkeys, the full D1 agonist C-APB (SKF 82958; 0.1-0.4 mg/kg s.c.)
      caused weak stimulation of locomotor activity. However, the motor stimulant
      effects of the D2 agonist (+)-PHNO (0.001 mg/kg s.c.) were not potentiated by C
      APB (0.3 mg/kg). Differences between these observations and expectations from
      experiments using rodents are discussed.

PMID- 1355408
TI  - Respiratory dyskinesia: a variety of clinical forms differentially diagnosed by
      using a spirograph.
AB  - Four cases of respiratory dyskinesia were investigated by using a spirograph
      before and after biperiden injection. The abnormal respiratory patterns in four
      cases appeared to be in two types and these abnormalities were abolished after
      biperiden injection. The present study showed that respiratory dyskinesia could
      be defined more clearly by using a spirograph and these results are useful for
      the diagnosis of patients with respiratory discomfort while undergoing
      neuroleptic drug treatment.

PMID- 1355409
TI  - The synaptic vesicle protein SV2 is a novel type of transmembrane transporter.
AB  - The primary function of synaptic vesicles is to store and release
      neurotransmitter. Synaptic vesicles are locally recycled following exocytosis and
      rapidly refilled with neurotransmitter from the cytoplasm by a process that
      depends on the electrochemical gradient generated by a proton pump. Little is
      known about the molecules that import neurotransmitter into synaptic vesicles. We
      report here that the sequence of the synaptic vesicle protein SV2 identifies this
      protein as a novel type of transmembrane transporter. The deduced amino acid
      sequence of SV2 contains two sets of six predicted transmembrane domains: the six
      most N-terminal transmembrane domains are highly homologous to a subfamily of
      transporters that includes the human glucose transporter, while the six most C
      terminal domains are homologous to the plasma membrane transporters for
      neurotransmitters. We propose that SV2 mediates transport of neurotransmitters
      into synaptic vesicles.

PMID- 1355410
TI  - Leukotriene B4 mediates shear rate-dependent leukocyte adhesion in mesenteric
      venules.
AB  - Previous studies have demonstrated that low shear rates promote leukocyte
      adherence to microvascular endothelium in postcapillary venules. The objective of
      this study was to determine whether an accumulation of inflammatory mediators
      such as platelet activating factor and leukotriene B4 is responsible for shear
      rate-dependent leukocyte-endothelial cell adhesion. Postcapillary venules (25-39
      microns in diameter) in cat mesentery were studied by intravital microscopy.
      Venular wall shear rate was varied over a wide range by graded occlusion of the
      mesenteric artery. Red blood cell velocity, vessel diameter, leukocyte rolling
      velocity, and the numbers of rolling and adherent leukocytes were measured at
      each shear rate. In one series of experiments, shear rate-dependent leukocyte
      adherence was monitored at different superfusion rates (1.0 and 2.5 ml/min). At
      the lower superfusion rate, the number of adherent leukocytes was significantly
      higher at any given shear rate when compared with results obtained at the higher
      superfusion rate. This suggests that reduced washout of inflammatory mediators
      contributes to shear rate-dependent leukocyte adhesion. Pretreatment with
      different platelet activating factor receptor antagonists (WEB 2086 or WEB 2170)
      had no effect on the number of adherent leukocytes normally observed at lower
      shear rates, suggesting that platelet activating factor does not play a major
      role in this process. However, shear rate-dependent leukocyte adhesion was
      largely prevented by pretreatment with either a leukotriene B4 receptor
      antagonist (SC-41930) or a leukotriene synthesis inhibitor (L663,536). The
      results of this study indicate that a reduced washout of leukotriene B4 is
      responsible for the enhanced leukocyte adherence that occurs at low venular wall
      shear rates.

PMID- 1355411
TI  - Report of the Conference on Low Blood Cholesterol: Mortality Associations.
AB  - BACKGROUND: A National Heart, Lung, and Blood Institute (NHLBI) Conference was
      held October 9-10, 1990, to review and discuss existing data on U-shaped
      relations found between mortality rates and blood total cholesterol levels (TC)
      in some but not other studies. Presentations were given from 19 cohort studies
      from the United States, Europe, Israel, and Japan. A representative of each study
      presented its findings and also submitted tables of proportional hazards
      regression coefficients for entry TC levels in regard to death, and these were
      incorporated into a formal statistical overview adjusted for age, diastolic blood
      pressure, cigarette smoking, body mass index, and alcohol intake, as available.
      METHODS AND RESULTS: The U-shape for total mortality in men and the flat relation
      in women resulted largely from a positive relation of TC with coronary heart
      disease death and an inverse relation with deaths caused by some cancers (e.g.,
      lung but not colon), respiratory disease, digestive disease, trauma, and residual
      deaths. Risk for combined noncardiovascular, noncancer causes of death decreased
      steadily across the range of TC. The conference considered possible explanations
      for the statistical associations found between low TC levels or active TC
      lowering and certain causes of death. One is that TC is lowered by some disease
      conditions themselves, such as wasting in chronic pulmonary disease or reduced
      production and secretion of cholesterol-bearing lipoproteins with liver disease.
      In this sort of situation, the TC:mortality association found in observational
      studies may be due to preexisting disease. This was addressed by excluding early
      deaths from the analysis, which did not change the results. The conference
      considered as well the biological function of cholesterol, which, if seriously
      deranged, might hypothetically cause a wide variety of diseases and dysfunction.
      The conference also considered the biological functions that might provide
      plausible mechanisms for the associations found. CONCLUSIONS: Definitive
      interpretation of the associations observed was not possible, although most
      participants considered it likely that many of the statistical associations of
      low or lowered TC level are explainable by confounding in one form or another.
      The conference focused on the apparent existence and nature of these associations
      and on the need to understand their source rather than on any pertinence of the
      findings for public health policy. Further research is recommended to explain the
      observed associations of low TC levels (and TC lowering) with certain
      noncardiovascular diseases. This includes studies of the time course of TC change
      in disease, the relation of TC to morbidity, further studies of possible
      epidemiological confounding, monitoring of population trends in TC and mortality,
      further studies of the relations in women, auditing of noncardiovascular events
      in trials, studies of cell membrane, genetic and molecular links to cholesterol
      metabolism, TC level and disease, studies of disease manifestations in specific
      lipid disorders, and further study of the proposed causal mechanisms linking low
      TC and hemorrhagic stroke.

PMID- 1355412
TI  - Coronary endothelial and cardiac protective effects of a monoclonal antibody to
      intercellular adhesion molecule-1 in myocardial ischemia and reperfusion.
AB  - BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is a major ligand on
      endothelial cells for adherence of activated polymorphonuclear leukocytes (PMNs).
      The major purpose of this study was to study the effects of RR1/1, a monoclonal
      antibody against ICAM-1 (i.e., MAb RR1/1), on myocardial injury and endothelial
      dysfunction associated with myocardial ischemia and reperfusion. METHODS AND
      RESULTS: Either MAb RR1/1 (2 mg/kg, n = 7), an antibody that was found to bind
      selectively to endothelial cells in the cat, or MAb R3.1 (2 mg/kg, n = 7), a
      nonbinding control antibody, was given as an intravenous bolus 10 minutes before
      reperfusion. Two hundred eighty minutes later, hearts were excised. The left
      ventricle area-at-risk (AAR) was similar in MAb RR1/1 (29 +/- 2%) and MAb R3.1
      (30 +/- 3%) groups. In MAb R3.1-treated cats, 90 minutes of myocardial ischemia
      plus 4.5 hours of reperfusion induced a significant myocardial injury (necrotic
      tissue/AAR, 28 +/- 2%), high myeloperoxidase activity (0.65 +/- 0.16 units/100 mg
      ischemic tissue), and a marked decrease in endothelium-dependent vasorelaxation
      in isolated left anterior descending coronary arteries (vasorelaxation to
      acetylcholine, 29 +/- 3%) with no change in endothelium-independent
      vasorelaxation (relaxation to NaNO2, 91 +/- 3%). However, cats treated with MAb
      RR1/1 developed significantly less myocardial necrosis (10 +/- 2% of the AAR, p
      less than 0.01), lower myeloperoxidase activity in ischemic myocardial tissue
      (0.2 +/- 0.03 units/100 mg ischemic tissue, p less than 0.01), and enhanced
      vasorelaxant responses to endothelial-dependent relaxation to acetylcholine (53
      +/- 5%) compared with ischemic/reperfused cats treated with Mab R3.1.
      Furthermore, addition of MAb RR1/1 in vitro significantly inhibited unstimulated
      PMN adherence to ischemic-reperfused coronary artery endothelium. CONCLUSIONS:
      These results suggest that ICAM-1-dependent PMN adherence plays an important role
      in reperfusion injury, and that PMN adherence and infiltration contribute
      significantly to coronary endothelial dysfunction.

PMID- 1355413
TI  - Mechanisms of interaction between the sulfhydryl precursor L-methionine and
      glyceryl trinitrate.
AB  - BACKGROUND: L-Methionine potentiates systemic hemodynamic effects of intravenous
      glyceryl trinitrate (GTN) in tolerant and nontolerant patients to a similar
      extent as N-acetylcysteine (NAC). This potentiation of GTN action by L-methionine
      has been attributed to enhanced intracellular formation of nitrosothiols, known
      to be potent stimulators of soluble guanylyl cyclase. This study was performed to
      analyze directly the effects of L-methionine on GTN-induced dilation of large
      epicardial arteries and the venous capacitance system of the dog in the tolerant
      and nontolerant states. Cultured rat aortic vascular smooth muscle cells and
      purified guanylyl cyclase were used to study potential intracellular and
      extracellular mechanisms responsible for this interaction. METHODS AND RESULTS:
      In awake nontolerant dogs, L-methionine (100 mg/kg) potentiated the tachycardic
      response to GTN (5.0 and 15 micrograms/kg/min) and enhanced the hypotensive
      action of GTN (1.5 and 5.0 micrograms/kg/min) in anesthetized, nonreflexic dogs.
      In nontolerant and tolerant dogs, however, L-methionine did not alter the dose
      response of large epicardial artery dilation to intravenous GTN challenges and
      did not modify nitrate tolerance of the low pressure system of the dog. The
      infusion of L-methionine (100 mg/kg) significantly increased plasma methionine
      levels (from 52 +/- 12 to 1,141 +/- 239 microM), cystine levels (from 12 +/- 4 to
      26 +/- 7 microM), but not homocystine levels. In vitro, the L-methionine
      conversion product L-cysteine (0.1-1.0 mM) but not homocysteine significantly
      enhanced the augmentation of purified guanylyl cyclase activity by GTN (100
      microM). Incubation of cultured rat aortic smooth muscle cells with L-methionine
      (10 microM or 1 mM) did not result in a significant increase of free
      intracellular sulfhydryl group content. CONCLUSIONS: The L-methionine conversion
      product L-cysteine mediates tolerance independent the potentiation of GTN action.
      This may result from an L-cysteine-induced formation of a vasoactive metabolite
      of GTN (nitric oxide) or nitrosothiol. This effect occurs primarily in the
      resistance vessel circulation, not in large epicardial arteries and veins. The
      lack of effect of L-methionine on sulfhydryl group content in large conductance
      vessels indicates that hepatic L-methionine metabolism constitutes the
      significant source of L-cysteine. These findings strongly suggest that
      administration of sulfhydryl-group precursor L-methionine does not represent a
      therapeutic alternative to a nitrate-free interval to restore nitrate sensitivity
      in tolerant large epicardial arteries and veins.

PMID- 1355414
TI  - Adrenergic agents: clinical trials and experiences.
AB  - Beta-adrenergic blocking agents constitute first-line therapy for hypertension in
      many countries of the world. Comparative trials have been extensive in duration
      and have included large numbers of patients. Still, the desired cardioprotective
      effect of beta blockers has yet to be established. Their antiatherosclerotic
      effect has been noted in several animal experiments. Confirming evidence is
      needed before the clinical relevance of this effect can be evaluated, but these
      studies point to a potential therapeutic effect that may be immensely important
      in the future. Beta blockers can reverse left ventricular hypertrophy secondary
      to hypertension, but it remains to be shown that regression of left ventricular
      hypertrophy will reduce the associated risks.

PMID- 1355415
TI  - A fragile X family with high penetrance in females: risk heterogeneity?
AB  - A fragile X family is described which shows two interesting features. In a
      sibship of seven, the two males and four of the five females are affected with
      mental retardation. Since the only normal daughter is not a carrier, the
      penetrance of the fragile X mutation in carrier daughters is 100%. Nevertheless,
      the penetrance of this syndrome in affected daughters of normal mothers has been
      estimated at a third. Also, DNA typing analysis of flanking RFLP markers revealed
      a higher than expected number of crossing-overs. We also include the molecular
      study of the mutation in the (CGG)n repeat of the FMR-1 gene.

PMID- 1355416
TI  - Amyloidogenic and non-amyloidogenic transthyretin Asn 90 variants.
AB  - Recently, a new transthyretin (TTR) variant was described in the normal
      Portuguese and German populations. The same substitution was found associated
      with familial amyloidotic polyneuropathy (FAP) in an American family of Italian
      origin. Comparative isoelectric focusing studies showed a difference in the
      mobility pattern between the non-pathogenic and pathogenic variants. However,
      comparative DNA sequencing between them did not reveal any additional mutation.
      Comparative isoelectric focusing between the variants and TTR Asn 90 produced by
      recombinant techniques indicated that the non-pathogenic variant has the
      electrophoretic behaviour expected for the mutation. We suggest that an as yet
      unknown post-translational modification may have occurred in the FAP-associated
      Asn 90 variant, turning it into an amyloidogenic molecule.

PMID- 1355417
TI  - Variable dystrophin expression in different muscles of a Duchenne muscular
      dystrophy carrier.
AB  - The majority of Duchenne muscular dystrophy (DMD) female carriers show dystrophin
      immunostaining abnormalities, although a significant proportion of clinically non
      manifesting carriers are normal following this analysis. We had the opportunity
      to study dystrophin immunostaining in two different muscles, the vastus lateralis
      and the rectus abdominis of a possible DMD carrier. While the vastus showed
      normal dystrophin immunostaining, pathological staining was detected in her
      rectus abdominis. These findings seem to indicate that dystrophin expression can
      vary in different muscle groups of a DMD carrier. The implications of these
      findings in DMD carrier detection and possible dystrophin function are discussed.

PMID- 1355418
TI  - Integrins, macrophages, and sarcoidosis.

PMID- 1355419
TI  - Disorders of excessive sleepiness. Treatment improves ability to stay awake but
      does not reduce sleepiness.
AB  - A total of 47 patients with sleep disorder (36 male and 11 female) with a mean
      age of 47.5 +/- 15 years were evaluated for daytime symptoms with a Multiple
      Sleep Latency Test (MSLT) and a Maintenance of Wakefulness Test (MWT) given on
      the same day--once at the time of their diagnostic evaluation and again after one
      to six months of treatment. The MSLT and MWT data are consistent with the notion
      that sleep tendency, as measured by the MSLT and ability to remain awake, as
      measured by the MWT, represent different physiologic processes. Data show a
      marked treatment-related improvement in ability to stay awake as measured by the
      MWT and no treatment-related improvement in sleepiness as measured by the MSLT.
      We conclude that there is a heterogeneous subpopulation of patients with sleep
      disorders whose symptoms of daytime sleepiness will show no treatment-related
      improvement in daytime symptoms if they are evaluated only by the MSLT. We
      suggest that, since ability to stay awake (and not ability to fall asleep) is a
      requisite for all job-related duties, an objective, physiologically based test
      such as the MWT should be used to assess the impact of sleep disorders in cases
      where there is a clinical concern about fitness to drive or work.

PMID- 1355421
TI  - Postimplantation development in the mouse. Symposium. London, 3-5 June 1991.

PMID- 1355420
TI  - Expression of alveolar macrophage adhesion molecules in pulmonary sarcoidosis.
AB  - Beta-2-integrins belong to a family of leukocyte surface glycoproteins that are
      essential for immune functions of bronchoalveolar cells. The expression of three
      alpha chains designed as CD11a, CD11b, CD11c, a common beta chain CD18, and of a
      ligand for several integrins CD54 (ICAM-1) was studied on alveolar macrophages of
      patients with active and inactive sarcoidosis and in control subjects. The
      percentage of macrophages expressing CD11b (CR3) was significantly increased in
      patients with active sarcoidosis compared with patients who had inactive disease
      and control subjects. The adhesion molecule CD54 (ICAM-1) was detected on a
      higher percentage of alveolar macrophages in patients with active rather than
      inactive sarcoidosis and in control subjects. Since integrin-mediated adhesion
      seems to be important in macrophage-lymphocyte interactions during the immune
      response, higher expression of both CD11b and CD54 on sarcoid alveolar
      macrophages may be related to several immune abnormalities reported in pulmonary
      sarcoidosis.

PMID- 1355422
TI  - Molecular mechanisms of pattern formation in the vertebrate hindbrain.
AB  - During early stages of neural development a series of repeated bulges, termed
      rhombomeres, form in the vertebrate hindbrain. Studies in the chick have shown
      that rhombomeres are segments that underlie the patterning of nerves in the
      hindbrain, and this raises the question of the molecular basis of segment
      development. Several genes have been found with expression patterns consistent
      with roles in the formation or differentiation of rhombomeres. The zinc finger
      gene Krox-20 is expressed in two alternating rhombomeres, r3 and r5, in the mouse
      hindbrain; these stripes of gene expression are established prior to the
      morphological appearance of segments. Krox-20 is also expressed in this pattern
      in the chick and Xenopus, suggesting that it has a conserved role, possibly in
      the formation of rhombomeres. Four members of the Hox-2 homeobox gene cluster
      have limits of expression at rhombomere boundaries. Three genes, Hox-2.6, -2.7
      and -2.8 have progressively more anterior limits of expression at two-segment
      intervals, whereas expression of Hox-2.9 is restricted to one rhombomere, r4. The
      Hox-2 genes are expressed in spatially restricted patterns in early neural crest
      cells. These findings suggest that the Hox genes have roles in specifying the
      identity of rhombomeres and of neural crest.

PMID- 1355423
TI  - To be or not to be Asp 57, that is the question.

PMID- 1355424
TI  - [Molecular biology of adaptive myocardial hypertrophy].

PMID- 1355425
TI  - Mechanism of platelet activating factor-induced vascular leakage in the rat
      trachea.
AB  - Platelet activating factor (PAF) is a phospholipid mediator of inflammation and
      vascular leakage that may be important in the etiology of asthma. We and others
      have demonstrated that PAF causes vascular leakage in the rat trachea. In the
      present study, we attempted to determine how PAF mediates this effect. Vascular
      leakage was quantitated by measuring the amount of intravascular Evans blue dye
      extravasated into tracheal tissue. Intravenously administered PAF increased
      vascular leakage, although Lyso-PAF and Enantio-PAF had no effect. PAF-induced
      vascular leakage was inhibited in a dose-dependent fashion by the PAF receptor
      blocker WEB 2086. However, PAF-induced vascular leakage was not inhibited by
      blockade of cyclooxygenase/lipoxygenase, calmodulin, calcium channels, protein
      kinase C, histamine receptors, or by destruction of peptidergic sensory nerves.
      We conclude that PAF causes vascular leakage in the rat trachea by a
      stereospecific receptor-mediated mechanism that does not depend on arachidonic
      acid metabolites, calcium, protein kinase C, histamine, or peptidergic sensory
      nerves.

PMID- 1355426
TI  - Effect of cetirizine, ketotifen and chlorpheniramine on the dynamics of the
      cutaneous hypersensitivity reaction: a comparative study.
AB  - Allergic cutaneous challenge causes mast cell and basophil mediator release which
      recruit inflammatory cells to the site of antigen administration. This secondary
      cell infiltration and mediator release is responsible for the changes seen during
      the late phase of allergic diseases. In this randomised, double-blind, cross
      over, placebo controlled study, it was demonstrated that, at steady-state drug
      concentrations, chlorpheniramine reduced the wheal-and-flare reaction by about
      50% compared to the 75% reduction, on average, by cetirizine and ketotifen.
      Cetirizine significantly reduced eosinophil vacuolisation at all observation
      periods, i.e. 2,6,10 and 24 h, and also inhibited basophil accumulation
      significantly at 10 h (75% reduction), while chlorpheniramine had a negligible
      effect on these variables. These changes would indicate that the late phase
      reaction was modified, especially as eosinophil vacuolisation is known to
      correlate with late phase intensity, T-lymphocyte infiltration and subsequent
      tissue damage. It further supports previous speculation that cetirizine inhibit
      late histamine release by acting on basophils. The extent of induration in the
      late phase reaction did not differ significantly among the three treatments.
      Cetirizine and ketotifen, noticeably although not significantly, reduced
      eosinophil and lymphocyte recruitment. As these two antihistamines differ
      structurally and in regard to receptor specificity, it is possible that they
      exert their actions on other, unspecified, receptors.

PMID- 1355427
TI  - Effects of loratadine and cetirizine on actual driving and psychometric test
      performance, and EEG during driving.
AB  - Sixteen healthy male and female volunteers took part in a 6-way, double-blind
      cross-over trial to compare the effects of single doses of cetirizine 10 mg,
      loratadine 10 mg and placebo, with and without alcohol (0.72 g.kg-1, lean body
      mass). Performance was measured in two repetitions of a psychometric test
      battery, and a standard, over-the-road driving test. EEG was also measured during
      driving. Alcohol significantly affected almost every performance measure and
      altered the EEG energy spectrum during driving whilst the blood concentrations
      declined from 0.37 to 0.20 mg.ml-1. The effects of cetirizine of on driving
      performance resembled those of alcohol. It caused the subjects to operate with
      significantly greater variability in speed and lateral position ('weaving'
      motion). The effects of alcohol and cetirizine appeared to be additive. Certain
      cetirizine-placebo differences in subjective feelings and test battery
      performance were also significant. Loratadine had no significant effect on any
      performance parameter. It was concluded that cetirizine, but not loratadine,
      generally caused mild impairment of performance after a single 10 mg dose.

PMID- 1355428
TI  - Interaction of talinolol and sulfasalazine in the human gastrointestinal tract.
AB  - The absorption of talinolol (TA) 50 mg was investigated without and together with
      the co-administration of sulfasalazine (SASP) 4 g in 11 healthy young volunteers,
      in order to clarify gastrointestinal transit of TA. Without SASP, the tmax of TA
      was 2.8 h, Cmax was 112 ng.ml-1 and the half life was 12 h; the AUCo-t was 958
      ng.ml-1.h. In the case of concomitant administration of SASP, TA was found only
      in serum from 3 individuals, with a Cmax of 23 ng.ml-1 and a mean AUCo-t of 84
      ng.ml-1.h. TA was not detectable in 5 subjects and it was at the limit of
      detection (2 ng.ml-1) in 3 subjects. Pharmacokinetic analysis was not possible in
      any of those individuals. The reason for the interaction appears to be the
      adsorption of TA by SASP. An interval of 2-3 h should elapse between giving SASP
      and other drugs.

PMID- 1355429
TI  - Heterogeneous susceptibility of human melanoma clones to monocyte cytotoxicity:
      role of ICAM-1 defined by antibody blocking and gene transfer.
AB  - Five clones derived from the same human malignant melanoma lesion were studied
      for their susceptibility to killing by human monocytes activated by exposure to
      interferon (IFN)-gamma and lipopolysaccharide. Melanoma clones were heterogeneous
      in their susceptibility to human monocyte cytotoxicity, with one clone (2/21)
      exhibiting extremely low levels of lysis. The different levels of susceptibility
      to monocyte cytotoxicity were not accounted for by susceptibility or resistance
      to monokines [tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6] because:
      (a) these effector molecules had little (TNF) or no (IL-1 and IL-6) cytolytic
      activity under these conditions; and (b) anti-TNF antibodies had marginal effects
      on cytotoxicity. Monocytes bound less to resistant than to susceptible melanoma
      cells. Monocyte-resistant 2/21 melanoma cells expressed substantially lower
      levels of ICAM-1 and VLA-4 than susceptible cells. Anti-CD18 and, to a lesser
      extent, anti-ICAM-1 mAb inhibited binding and cytotoxicity of human monocytes on
      malignant melanoma whereas anti-VLA-4 had no inhibitory action. Transfection of
      the ICAM-1 gene under the control of a constitutive promotor resulted in high
      levels of expression of ICAM-1 in 2/21 melanoma cells and, concomitantly, in
      augmented susceptibility to activated monocyte cytotoxicity. The augmented
      killing of ICAM-1 transfected 2/21 cells was inhibited by anti-ICAM-1 mAb. These
      results demonstrate that the CD18-ICAM-1 adhesion pathway can play an important
      role in the expression of human monocyte cytotoxicity on melanoma target cells
      and that heterogeneity in expression of ICAM-1 can underlie differences in
      susceptibility to tumoricidal activity.

PMID- 1355431
TI  - Molecular cloning and exon-intron mapping of the gene encoding human
      transmembrane secretory component (the poly-Ig receptor)
AB  - Secretory component (SC or the poly-Ig receptor) plays a crucial role in mucosal
      immunity by translocating polymeric IgA and IgM through secretory epithelial
      cells into external body fluids. Labeled restriction fragments from human SC cDNA
      were used to screen a human genomic leukocyte library. Three overlapping clones,
      spanning a total of 19 kb of the human SC gene, including 3 kb of the 5' flanking
      region, were characterized. The putative TATA box candidate, preceded by a CAAT
      like box, was found 329 nucleotides upstream of the first exon. Altogether 11
      exons covering the entire coding region were identified. The exon size ranged
      from 59 to 657 nucleotides and exon-intron junctions followed known consensus
      sequences. Three of the five extracellular Ig-related domains (D1, D4 and D5)
      were confined to one exon each (E3, E5 and E6), whereas D2 and D3 were encoded by
      the same exon (E4). The latter exon corresponds to that involved in alternate
      splicing of rabbit SC. The membrane-spanning segment was confined to part of one
      exon (E8). The cytoplasmic tail was encoded by four exons (E8-E11), whose
      boundaries encompassed fairly well the structural determinants proposed to be
      responsible for intracellular sorting of SC in the rabbit. The polymorphic
      restriction site reported earlier for Pvu II was localized to the third intron.

PMID- 1355430
TI  - Functional maturation of recent thymic emigrants in the periphery: development of
      alloreactivity correlates with the cyclic expression of CD45RC isoforms.
AB  - The transition from fully developed CD4+CD8- single-positive (SP) thymocytes into
      fully mature recirculating peripheral T cells is both poorly understood with
      regard to the expression of restricted isoforms (CD45R) of the leukocyte common
      antigen and in terms of T cell function. The present investigation monitored the
      extrathymic development of CD4+CD8- SP thymocytes in euthymic recipients using
      allotype-marked donor cells and monoclonal antibody OX22 which recognizes an
      epitope on the C exon of rat CD45R. We established that donor-derived cells in
      the blood 1 day later bore the phenotype of the injected SP thymocytes (CD4+ Thy
      1+ CD45RC-). T cells with the identical phenotype were also present in the
      thoracic duct lymph of uninjected rats, suggesting that the Thy-1+ CD45RC- T
      cells represent recent thymic emigrants (RTE) which have migrated to the
      periphery of their own accord. During extrathymic maturation donor-derived
      peripheral RTE lost Thy-1 within 3 days and expressed the CD45RC+ high molecular
      weight isoform by day 7; between days 8 and 14 a proportion (25%-30%) of the
      donor cells once again lost the high molecular weight isoform (CD45RC-). The
      transition of SP (CD45RC-) thymocytes to fully mature CD45RC+ CD4 T cells via
      intermediate peripheral RTE was accompanied at each stage by an increased ability
      of the maturing T cells to induce skin allograft rejection. Unexpectedly, the
      subsequent loss of the high molecular weight isoform, following presumed antigen
      encounter, was associated with a significant reduction in the ability of this Thy
      1-CD45RC- subpopulation to effect graft rejection. The cyclic expression of
      CD45RC isoforms on both immature and mature CD4 T cells and the fact that the low
      molecular weight isoform was found in the periphery on both RTE (unquestionably
      naive) and antigen-experienced CD4 T cells, makes it unlikely that this isoform
      uniquely identifies memory T cells, at least in the rat.

PMID- 1355433
TI  - Macrophage-induced cytotoxicity of N-methyl-D-aspartate receptor positive neurons
      involves excitatory amino acids rather than reactive oxygen intermediates and
      cytokines.
AB  - The co-localization of activated macrophages and damaged neurons observed in
      brain injury and degenerative brain diseases may hint to macrophage-induced
      neuronal cytotoxicity. Recently, macrophages have been found to secrete
      neurotoxic molecules such as radical oxygen intermediates and glutamate, the
      latter interacting with N-methyl-D-aspartate (NMDA) receptors. As shown in the
      present study, brain macrophages termed microglial cells co-cultured with
      differentiated cerebellar neurons excert potent neurotoxic effects. Neurotoxicity
      is unlikely to be due to cytokines since tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-1 beta, IL-6 and interferon (IFN)-alpha/IFN-beta/IFN-gamma had
      no such effects. In contrast, when treating neurons with H2O2 or oxygen radical
      generating systems cytotoxicity was induced. Furthermore, microglia were found to
      produce O2- and H2O2 when triggered with phorbol 12-myristate 13-acetate.
      However, in co-cultures of neurons and microglia, oxygen-radical scavengers
      catalase and superoxide dismutase, failed to protect neurons from microglia
      induced killing. Moreover, when using undifferentiated neurons which are
      susceptible to H2O2 but not to NMDA receptor-dependent killing, microglia did not
      destroy the neurons. Thus, the amount of reactive oxygen intermediates produced
      by microglia in co-culture do not reach the critical concentrations required for
      neurotoxicity. As dibenzocyclohepteneimide, an antagonist to NMDA receptors
      neutralized neurotoxicity in microglia-neuronal co-cultures, excitatory amino
      acids released by microglia are suggested to compose the major determinant of
      neurotoxicity.

PMID- 1355432
TI  - Identification of a surface protein (p100) associated with two glycosyl
      phosphatidylinositol-linked molecules (Thy-1 and ThB) by natural anti-lymphocyte
      autoantibodies.
AB  - Our previous study of natural autoantibodies showed that anti-lymphocyte
      antibodies are frequently produced by perinatal B cells from normal strains of
      mice. One-third of these monoclonal antibodies (mAb) recognized similar epitopes
      on the surface of thymocytes. In the present report, we have characterized the
      molecule recognized by three of these mAb (D10, G7, 22). These mAb identified a
      100-kDa protein (p100) on the surface of thymocytes. This protein resolved into
      70-kDa polypeptide chains under reducing conditions. Inhibition experiments as
      well as antibody immunoprecipitations in the presence of mild detergents revealed
      non-covalent association of the p100 with Thy-1 and ThB. A similar multimolecular
      complex was identified following chemical cross-linking of thymocyte surface
      proteins. Analysis of several Thy-1-defective mutant cells lines, and thymocytes
      treated with phosphatidylinositol-specific phospholipase C (PI-PLC) showed that
      the expression of p100 was strongly influenced by Thy-1 molecule. The p100 was
      resistant to PI-PLC treatment and was not released into the supernatant as was
      the case for Thy-1 and ThB molecules. These data lead us to propose that the p100
      is a transmembrane protein, the expression of which in the plasma membrane is
      dependent on the association or presence of Thy-1 molecule.

PMID- 1355434
TI  - Stereoselective R-(+) enantiomer of HA-966 displays anxiolytic effects in
      rodents.
AB  - Anxiolytic agents disinhibit suppressed behaviors in rodents in preclinical
      models of anxiety such as the non-conditioned social interaction and elevated
      plus maze assays and the conditioned conflict Cook and Davidson procedure. The
      (+) and (-) enantiomers of (+/-)-3-amino-1-hydroxy-2-pyrrolidinone (HA-966) have
      been resolved and revealed that R-(+)-HA-966 significantly disinhibits both non
      conditioned and conditioned suppressed behavior similar to the benzodiazepine
      diazepam, while the S-(-) enantiomer was devoid of anxiolytic activity and only
      produced behavioral sedation. Furthermore, R-(+)-HA-966 lacked side-effects in
      rodents commonly associated with the administration of benzodiazepines such as
      motor incoordination and ataxia, significant interactions with ethanol, and
      amnesia. These data suggest that R-(+)-HA-966, an antagonist at the strychnine
      insensitive glycine/NMDA receptor site, was anxioselective and lacked some of the
      side-effects associated with benzodiazepine anxiolytics.

PMID- 1355435
TI  - Effects of selective tachykinin receptor antagonists on capsaicin- and tachykinin
      induced bronchospasm in anaesthetized guinea-pigs.
AB  - Bronchospasm induced by i.v. injection of equieffective doses of acetylcholine,
      capsaicin or selective tachykinin receptor agonists ([Sar9]SP sulfone or [beta
      Ala8]neurokinin A (NKA-4-10)) (for NK1 and NK2 receptors, respectively) was
      studied in anaesthetized guinea-pigs. The NK1 and NK2 receptor antagonists, (+/-)
      CP96,345 (3 mumol/kg i.v.) and MEN 10,376 (3 mumol/kg i.v.), selectively
      abolished the bronchoconstriction induced by the respective agonist, showing that
      both NK1 and NK2 receptors mediate bronchoconstriction in guinea-pig airways and
      that they are activated independently. Capsaicin-induced bronchospasm was
      inhibited by atropine (1.5 mumol/kg i.v.) and MEN 10,376 (3 mumol/kg i.v.), but
      unaffected by (+/-)-CP96,345 (3 mumol/kg i.v.). Hexamethonium (79 mumol/kg i.v.),
      propranolol (17 mumol/kg i.v.) and physostigmine (0.9 mumol/kg i.v.) enhanced the
      airway constriction induced by acetylcholine, capsaicin, [Sar9]SP sulfone or
      [beta-Ala8]NKA-(4-10) while guanethidine (67 mumol/kg s.c. for two days)
      increased only bronchoconstriction induced by capsaicin or the selective NK2
      receptor agonist. In hexamethonium-treated animals, MEN 10,376 still abolished
      the increase in insufflation pressure induced by [beta-Ala8]NKA-(4-10) and
      reduced the increase elicited by capsaicin. In summary, in anaesthetized guinea
      pig i.v. capsaicin-induced bronchospasm through activation of postjunctional NK2
      (but not NK1) receptors along with activation of cholinergic pathways. This motor
      response is moderated by the simultaneous stimulation of a sympathetic
      bronchodilating mechanism(s), possibly through activation of NK2 receptors
      localized in sympathetic ganglia.

PMID- 1355436
TI  - Antidepressant and anxiolytic effects of alprazolam versus the conventional
      antidepressant desipramine and the anxiolytic diazepam in the forced swim test in
      rats.
AB  - The antidepressant and anxiolytic effects of alprazolam were compared to those of
      desipramine, diazepam and buspirone in the forced swim test. Subchronic
      alprazolam induced a reduction in immobility similar to that of desipramine in
      'non-pretested' and 'pretested' rats. In 'non-pretested' rats, the anti
      immobility effect of desipramine was potentiated by diazepam and alprazolam,
      given before subchronic desipramine, while the anti-immobility effect of
      subchronic alprazolam was counteracted by diazepam. Diazepam, administered before
      the pretest session, counteracted, 24 h later, the anti-immobility effect of
      subchronic desipramine and alprazolam; alprazolam counteracted the anti
      immobility effect of alprazolam but not of desipramine, buspirone at the highest
      doses tested potentiated the anti-immobility effect of subchronic desipramine but
      not of alprazolam. These data provide further support for the hypothesis that the
      GABA/benzodiazepine/Cl complex is directly implicated in the action of
      antidepressants and that systems other than the GABA system are involved in the
      antidepressant and anxiolytic effects of alprazolam.

PMID- 1355437
TI  - Carvedilol, a new beta-adrenoceptor antagonist and vasodilator antihypertensive
      drug, inhibits superoxide release from human neutrophils.
AB  - Carvedilol produced a dose-dependent inhibition of superoxide (O2-) release from
      human neutrophils (PMNs) (IC50 = 28 microM) and scavenged O2- generated during
      dihydroxyfumaric acid (DHF) autooxidation (IC50 = 41 microM). Other beta
      blockers, such as celiprolol, labetalol and atenolol, or the antioxidant,
      'lazaroid', U74500A had no effect on O2- either released from PMNs or generated
      during DHF autooxidation. Propranolol, at 0.3 mM, inhibited O2- release from PMNs
      (73%) but failed to scavenge O2- generated from DHF. The novel free radical
      scavenging effect of carvedilol may contribute to the cardioprotective activity
      of the compound.

PMID- 1355438
TI  - Weak anticonvulsant activity of CGP 37849 and CGP 39551 against kindled seizures
      following systemic administration.
AB  - The anticonvulsant and behavioural actions of CGP 37849 and CGP 39551, two novel
      competitive NMDA receptor antagonists, were examined in fully amygdala kindled
      rats following systemic administration. Only weak anticonvulsant effects were
      observed following either i.p. or i.v. injection of the antagonists. Moreover,
      behavioural abnormalities (ataxia, hyperactivity, muscular hypotonia) were
      apparent at all anticonvulsant doses. These results suggest that CGP 37849 and
      CGP 39551 may be of limited therapeutic usefulness against complex partial
      seizures in man, the seizure type showing greatest refractoriness to presently
      available medication.

PMID- 1355439
TI  - Characterization of [3H]atipamezole as a radioligand for alpha 2-adrenoceptors.
AB  - Atipamezole (MPV-1248, 4-(2-ethyl-2,3-dihydro-1H-inden-2-yl)-1H-imidazole), a
      potent alpha 2-adrenoceptor antagonist, was tritiated to high specific activity.
      We then compared [3H]atipamezole and [3H]rauwolscine as radioligands for alpha 2
      adrenoceptors in rat cerebral cortex, neonatal rat lung, and human platelets. (-)
      Noradrenaline and phentolamine were used to define specific alpha 2-adrenergic
      binding. Unlabelled atipamezole was used in a similar manner to define saturable,
      high-affinity non-adrenergic binding. [3H]Atipamezole binding to human platelets
      (Kd 1.3 nM) and rat brain membranes (Kd 0.5 nM) equilibrated rapidly and was
      displaced in the expected manner by alpha 2-adrenergic ligands. In contrast,
      [3H]atipamezole binding in neonatal rat lung membranes was only effectively
      inhibited by unlabelled atipamezole, and by high concentrations of idazoxan. The
      total density of binding sites for [3H]atipamezole was clearly in excess of the
      density of alpha 2-adrenoceptors in this tissue, as defined by [3H]rauwolscine
      binding. We conclude that [3H]atipamezole binds with high affinity to alpha 2
      adrenoceptors in human platelets and rat cerebral cortex, and that the compound
      can be used to investigate alpha 2-adrenoceptor properties and drug actions in
      these tissues. In neonatal rat lung, [3H]atipamezole identified an additional
      population of binding sites, distinct from both classical alpha 2-adrenoceptors
      and idazoxan-defined imidazoline receptors. The pharmacological identity of these
      binding sites remains to be elucidated. This non-adrenergic component in the
      binding characteristics of [3H]atipamezole complicates its use as a general alpha
      2-adrenoceptor radioligand.

PMID- 1355440
TI  - Synergistic behavioural effects of dopamine D1 and D2 receptor agonists are
      determined by circadian rhythms.
AB  - The effects of continuous subcutaneous infusions of rats for 336 h with vehicle,
      SKF 38393 (a dopamine D1 receptor agonist), (+)-4-propyl-9-hydroxynaphthoxazine
      (PHNO, a dopamine D2 receptor agonist) or both D1 and D2 receptor agonists, on
      locomotor activity were investigated. Rats were maintained under constant
      lighting conditions, either continuous dark (dark:dark) or continuous light
      (light:light), before and during drug treatments in order to determine the
      influence of free-running circadian rhythms on drug responses. The D2 receptor
      agonist initially increased locomotion in rats kept under dark:dark during both
      subjective night (period of maximum locomotion) and day (period of minimum
      locomotion), but had no effect in rats maintained in light:light throughout the
      336 h of treatment. The motor stimulant effects of the D2 receptor agonist on
      rats kept in dark:dark increase during the course of treatment during subjective
      night (sensitization), but decreased during the rats' subjective day (tolerance).
      The D1 receptor agonist, SKF 38393, had no effect on its own regardless of the
      lighting conditions and the duration of treatment. However, the D1 receptor
      agonist interacted synergistically with the D2 receptor agonist in rats
      maintained under light:light, depending on the duration of treatment. Synergistic
      effects were also observed on initiation of treatment in rats under dark:dark but
      only during subjective day. Tolerance to the synergistic effects of the receptor
      agonists occurred as a function of treatment duration, but only during subjective
      day. The D1 receptor agonist blocked the effects of the D2 receptor agonist
      during the rats' subjective night after 100 h of treatment, but not after 25 or
      325 h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355442
TI  - In vivo binding to dopamine receptors: a correlate of potential antipsychotic
      activity.
AB  - Antagonists of dopamine receptors (especially those of the D2 subtype) have long
      been recognized as effective antipsychotics. SCH 39166, a dopamine D1 selective
      antagonist, is now also being evaluated for its clinical antipsychotic
      properties. The studies described herein determine the binding affinity of a
      variety of dopamine receptor antagonists (both dopamine D1 and D2 selective
      compounds) for the dopamine D1 and D2 receptors, in vivo, and correlate this
      affinity with their behavioral activity in the rat conditioned avoidance response
      (CAR) test. The in vivo binding affinities of the D1 selective compounds at the
      dopamine D1 site exhibited a high correlation (r = 0.97) with their activities in
      the rat CAR test. Likewise, D2 selective compounds' inhibition of in vivo binding
      to dopamine D2 receptors correlated with their behavioral potencies (r = 0.98).
      Conversely, any binding of selective agents to their non-targeted receptor did
      not correlate with their behavioral activity. These data suggest that in vivo
      binding to either dopamine D1 and/or D2 receptors is predictive of potential
      antipsychotic efficacy.

PMID- 1355443
TI  - Inhibition of morphine antinociception by centrally administered histamine H2
      receptor antagonists.
AB  - The actions of zolantidine dimaleate and five other histamine H2 receptor
      antagonists, given into the lateral ventricle of rats, were assessed on
      nociceptive responses in the presence and absence of systemically administered
      morphine. On the tail flick response, zolantidine induced a time- and dose
      dependent inhibition of morphine antinociception, with no effect on responses in
      the absence of morphine. Zolantidine and another H2 receptor antagonist,
      tiotidine, also inhibited morphine responses in the hot plate test. Four other H2
      receptor antagonists of varying structure, brain-penetrating ability, and H2
      potency also induced dose-related inhibition of morphine tail flick responses.
      Over three orders of magnitude, the potency of these compounds as inhibitors of
      morphine antinociception was highly correlated with H2 receptor antagonist
      potency (r = 0.98, P less than 0.005, n = 5). Taken with previous studies showing
      the selectivity of these compounds for histamine H2 receptors, and the
      antinociceptive properties of histamine, these results strongly suggest a role
      for brain histamine H2 receptors in the expression of morphine antinociception.

PMID- 1355441
TI  - The antinociceptive actions of dexmedetomidine on dorsal horn neuronal responses
      in the anaesthetized rat.
AB  - The actions of the selective alpha 2-adrenoceptor agonist dexmedetomidine were
      examined on the nociceptive C and innocuous A beta fibre-evoked responses of
      dorsal horn neurones to transcutaneous electrical stimulation in the intact
      anaesthetized rat. C fibre-evoked responses were dose dependently reduced by
      intrathecal dexmedetomidine--to a maximum 86 +/- 6% inhibition by 10 micrograms
      of the agonist. The ED50 for inhibition of C fibre responses was estimated to be
      2.5 micrograms. A beta-evoked responses were inhibited to a lesser degree--a
      maximum 54 +/- 8% inhibition after 10 micrograms dexmedetomidine. The
      antinociceptive effects of dexmedetomidine were reversed by the alpha 2
      adrenoceptor antagonist atipamezole and the opioid antagonist naloxone. The
      results are discussed with reference to adrenergic and opioid mechanisms in the
      spinal cord.

PMID- 1355444
TI  - HS-142-1, a novel nonpeptide atrial natriuretic peptide (ANP) antagonist, blocks
      ANP-induced renal responses through a specific interaction with guanylyl cyclase
      linked receptors.
AB  - HS-142-1, a novel microbial product, blocked 125I-labeled rat atrial natriuretic
      peptide (rANP) (= ANF(99-126)) binding to bovine adrenocortical membranes, where
      guanylyl cyclase-containing receptors are predominantly expressed. However, HS
      142-1 only slightly inhibited [125I]rANP binding to bovine lung membranes where
      only a small portion of binding sites are coupled to guanylyl cyclase. Further,
      HS-142-1 only recognized the 135 kDa ANP receptor, which is considered to be the
      guanylyl cyclase-containing receptor based on the results obtained in affinity
      cross-linking studies with bovine adrenocortical and lung membranes. Under
      identical conditions, Atriopeptin I selectively recognized guanylyl cyclase-free
      receptors both in binding and affinity cross-linking experiments. When injected
      intravenously (1 mg/kg) to anesthetized rats, HS-142-1 abolished ANP-induced
      diuresis and natriuresis. These results suggest that HS-142-1 works in vivo
      through a specific interaction with the ANP functional receptor, and that HS-142
      1 will be a powerful tool for understanding the physiological roles of ANP in
      distinction from its pharmacological effects.

PMID- 1355445
TI  - Mapping rat brain structures activated during ethanol withdrawal: role of
      glutamate and NMDA receptors.
AB  - Brain structures activated during ethanol withdrawal have been mapped by
      visualizing c-fos mRNA expression. The regional distribution of c-fos mRNA in
      brain during ethanol withdrawal can be mimicked by acute injection of N-methyl-D
      aspartic acid (NMDA) and is stereospecifically blocked by the NMDA receptor
      antagonist, MK-801. The findings reveal that the dentate gyrus and piriform
      cortex are selectively activated during ethanol withdrawal and suggest that this
      may be mediated by glutamate activation of NMDA receptors.

PMID- 1355446
TI  - NMDA receptor activation stimulates phospholipase A2 and somatostatin release
      from rat cortical neurons in primary cultures.
AB  - We have recently shown that glutamate exerts a stimulatory action on somatostatin
      secretion in cortical neurons essentially through NMDA receptor sites. Here, we
      investigated whether arachidonic acid release could be modified after NMDA
      receptor activation in cortical neurons in primary culture. We also studied
      whether pharmacological manipulation of phospholipase A2 could modify
      somatostatin release. We found that both glutamate and NMDA (N-methyl-D
      aspartate) stimulated [3H]arachidonic acid release. NMDA-evoked arachidonic acid
      release was inhibited by MK-801 and TCP (two NMDA receptor-type antagonists), or
      by mepacrine, an inhibitor of phospholipase A2. NMDA-induced somatostatin release
      was inhibited by MK-801, mepacrine and by another phospholipase A2 inhibitor, p
      bromophenacylbromide (pBPB). However, responses to NMDA were unaffected by H7,
      NDGA (nordihydroguaiaretic acid), indomethacin or by RHC 80267 (inhibitors of
      protein kinase C, lipooxygenase, cyclooxygenase and diacylglycerol lipase,
      respectively). Mepacrine (greater than or equal to 100 microM) decreased NMDA
      stimulated phosphatidylinositol (PI) hydrolysis and at higher concentrations (250
      microM) was also able to inhibit basal release whereas pBPB had no effect in the
      range of concentrations tested. Neomycin (which inhibits phosphatidylinositol
      metabolism by binding strongly and selectively to inositol phospholipids) reduced
      by 30% the NMDA-stimulated somatostatin release, although chronic treatment of
      neurons with the phorbol ester 12-myristate, 13-acetate (PMA) had no effect on
      this response. Melittin, an activator of phospholipase A2, was able to stimulate
      both arachidonic acid release and somatostatin secretion. High-performance liquid
      chromatography (HPLC) analysis of tritiated metabolites released from cortical
      neurons under basal or NMDA-stimulated conditions revealed that [3H]arachidonic
      acid was the only metabolite detectable. Furthermore, external addition of
      arachidonic acid increased somatostatin secretion. Our results show a correlation
      between the two parameters studied.

PMID- 1355447
TI  - Involvement of D-amino acid oxidase in elimination of D-serine in mouse brain.
AB  - The physiological role of D-amino acid oxidase (EC 1. 4. 3. 3) in mouse brain is
      described. The presence of D-enantiomers of neutral common amino acids was
      surveyed in the brain. D-serine was shown to be present at high concentration
      only in regions where the enzyme activity was low. In normal mice whose D-amino
      acid oxidase activity was much higher in the cerebellum than in the cerebrum,
      free D-serine content was apparently lower in the cerebellum than in the
      cerebrum. In mice of a mutant strain lacking D-amino acid-oxidase activity, the
      free D-serine level was remarkably high both in the cerebrum and cerebellum. The
      results suggest that the enzyme is involved in the elimination of free D-serine
      in the cerebellum.

PMID- 1355449
TI  - 6th Congress of the European Society of Surgical Oncology. Helsinki, June 10-13,
      1992. Abstracts.

PMID- 1355450
TI  - D-amino-acid oxidase and its physiological function.

PMID- 1355448
TI  - Site-directed mutagenesis of active-site-related residues in Torpedo
      acetylcholinesterase. Presence of a glutamic acid in the catalytic triad.
AB  - Site-directed mutagenesis was used to investigate the role of acidic amino acid
      residues close to the active site of Torpedo acetylcholinesterase. The recently
      determined atomic structure of this enzyme shows the conserved Glu-327, together
      with His-440 and Ser-200 as forming a catalytic triad, while the adjacent
      conserved Asp-326 points away from the active site. Transfection of appropriately
      mutated DNA into COS cells showed that the mutation of Asp-326----Asn had little
      effect on catalytic activity or the molecular forms expressed, suggesting no
      crucial structural or functional role for this residue. Mutation of Glu-327 to
      Gln or to Asp led to an inactive product. These results support the conclusions
      of the structural analysis for the two acidic residues.

PMID- 1355451
TI  - Myofibrillar and membrane-bound enzymes in skeletal muscle from myodystrophic
      mice.
AB  - 1. Experiments were carried out to examine the biochemical changes, such as
      contractile protein biochemistry and membrane bound enzyme alterations associated
      with skeletal muscles of myd/myd. 2. Our studies demonstrate that there was a
      progressive decline in myofibrillar ATPase activity, and this decrease is
      greatest in 30 weeks old animals of myd/myd as compared to controls. 3. The
      proteolytic activity of myofibrils isolated from myd/myd was significantly higher
      than controls. 4. There was no significant difference in Ca2+ ATPase activity of
      myosin and actin-activated myosin ATPase activity of myd/myd and their controls.
      5. Mg2+ ATPase and Na(+)+K(+)-ATPase of myodystrophic SL showed significant
      increase compared to controls. 6. Isoproterenol stimulated adenylate cyclase
      activity was significantly lower in the SL of dystrophic mice compared to
      controls. 7. GTP+isoproterenol stimulate adenylate cyclase was significantly
      higher in control SL and SR when compared to SL and SR isolated from myd/myd. 8.
      Guanylate cyclase activity was greater in myodystrophic mice both in the absence
      and presence of Triton X-100. cGMP and cAMP phosphodiesterase activities were
      greater in dystrophic mice as compared to controls. 9. These observations suggest
      that there are significant changes in myofibrillar ATPase, myofibrillar protease
      and membrane bound enzymes of myd/myd compared to control.

PMID- 1355452
TI  - Effect of temperature and pH on factor XIIIa from human placenta.
AB  - 1. The activation of the native enzyme was achieved by a proteolytic procedure
      involving thrombin. 2. The pH profile was independent of the nature of the
      substrates assayed (casein or dimethylcasein plus putrescine). The optimum pH was
      between 7.6 and 7.9 and the pK values were 6.5/7 and 8.7/9. A cysteinyl residue
      appeared to be involved in the pH-dependence activity. 3. In the presence of
      calcium, the thermostability of enzyme was increased: the temperature at which
      enzyme lost half of its activity increased up to 7 degrees C. 4. The kinetics of
      the thermal deactivation of F XIIIa depended on the presence or absence of
      calcium. 5. In its presence the reaction obeyed second order kinetics, while in
      its absence, the kinetics were of first order. In the first case, the
      irreversible thermal deactivation could be described by a two-step mechanism (N--
      -X----D) while in the second case, the deactivation followed the simple model (N-
      --D). 6. Neither divalent cations like Sr2+, Ba2+, Mg2+, nor bovine serum-albumin
      and polyhydric alcohols were able to increase the thermostability of F XIIIa. 7.
      Thermal deactivation of F XIIIa did not appear linked to the redox state of
      enzyme, nor to the modification of SH groups. 8. We observed a good correlation
      between the loss of activity and the unfolding of the polypeptide chain of F
      XIIIa during heating. 9. The optimum temperature of F XIIIa activity was 40
      degrees C at pH 8 and 45 degrees C at pH 7.

PMID- 1355453
TI  - Diethylnitrosamine-induced increase in gamma-glutamyltranspeptidase in rat liver:
      its association with thyroid hormone deficiency and its reversal by tri
      iodothyronine.
AB  - 1. The nodular phase of hepatic premalignancy was induced in male Fischer 344
      rats by the administration of diethylnitrosamine, 200 mg/kg i.p., followed by
      promotion utilizing the Solt-Farber promoting regime. 2. Relative to the
      situation in normal non-treated control rats: the activity of gamma
      glutamyltranspeptidase was found to be increased 9.42-fold in homogenate and 7.33
      fold in plasma membrane fractions prepared from the livers of saline-injected
      control rats; and 81.37-fold in homogenates and 91.92-fold in plasma membranes
      prepared from the livers of diethylnitrosamine-injected rats; plasma levels of
      total T3 and total T4 were found to be decreased 42.06 and 47.45% in saline
      injected control rats and 88.7 and 83.2% in diethylnitrosamine-injected rats,
      respectively. 3. An early pre-nodular phase of hepatic premalignancy was produced
      in young immature and mature adult male Fischer 344 rats by the administration of
      diethylnitrosamine, 75 mg/kg, without subsequent application of the promotion
      regime. 4. Relative to the situation in control rats: the activity of gamma
      glutamyltranspeptidase was found to be increased in liver homogenates prepared
      from diethylnitrosamine-treated rats, 1.62-fold in young immature rats 1.20-fold
      in mature adult rats; plasma levels of total T3 were found to be reduced in
      diethylnitrosamine-treated rats, 28% in young immature rats 9% in mature adult
      rats. 5. Treatment of diethylnitrosamine-injected young immature male Fischer 344
      rats at the prenodular phase of hepatic premalignancy with tri-iodothyronine at
      0.005 micrograms/kg s.c. daily for 7 days reversed the diethylnitrosamine-induced
      increase in liver homogenate gamma-glutamyltranspeptidase activity and the
      decrease in plasma total T3, restoring these parameters to normal
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355454
TI  - Characterization of the Bacillus subtilis CwbA protein which stimulates cell wall
      lytic amidases.
AB  - The Bacillus subtilis cell wall binding protein, CwbA, stimulated the cell wall
      lytic activities of the B. subtilis and B. licheniformis autolysins (CwlA and
      CwlM, respectively) in addition to that of the major B. subtilis autolysin
      (CwlB). Even though the substrate for the enzyme reaction was changed from B.
      subtilis cell wall containing a teichoic acid to Micrococcus luteus cell wall
      containing a teichuronic acid, the stimulatory effect of CwbA on CwlA activity
      was observed.

PMID- 1355455
TI  - Reconstruction and expression of the autolytic gene from Clostridium
      acetobutylicum ATCC 824 in Escherichia coli.
AB  - The complete lyc gene encoding the autolytic lysozyme of Clostridium
      acetobutylicum ATCC 824 was reconstructed from two overlapping DNA fragments and
      cloned into a suitable plasmid enabling Escherichia coli to produce this lytic
      enzyme under the control of the lac promoter. A polypeptide with an apparent M(r)
      of 35,000, corresponding to that predicted from the nucleotide sequence, was
      observed by maxicell analysis of whole-cell extracts of E. coli harboring the
      clostridial gene. The enzyme yield was shown to depend on the pH of the culture
      medium, since the protein was unstable at alkaline pH. The expression of the lyc
      gene was not increased by using the E. coli strong promoter, lpp-lac, probably
      due to the limit imposed by the extreme differences in codon usage. Although the
      LYC lysozyme does not contain a cleavable signal peptide, most of the protein was
      found in the periplasmic fraction of E. coli suggesting that this enzyme was
      secreted through a specific mechanism, as already observed for other autolysins.

PMID- 1355456
TI  - RFLPs for somatotropic genes identify quantitative trait loci for growth in mice.
AB  - Restriction fragment length polymorphisms for somatotropic genes were tested for
      associations with body weight and postweaning growth rate in mice. Polymorphisms
      for growth hormone (GH) and insulin-like growth factor 2 (IGF-2) genes were
      identified in stock population lines which had been subjected to long-term
      selection for high 42-day body weight (H lines) or randomly mated (FP and C
      lines). Two F2 populations of mice (5F2 and MF2) were generated from crosses
      between a single H line of mice and two unselected control lines and
      subsequently, two divergently weight selected sublines were generated from each
      F2 population. The GHh allele which had originally been fixed in three of four H
      lines and absent from all FP and C lines was found to have a significant (P less
      than 0.01) effect on 42-day weight and postweaning growth rate in the F2
      populations. However, GHh was associated with lower 42-day weight in the F2
      populations, suggesting that the positive association between GHh and weight in
      the stock population was unique to the high weight selected genetic background of
      those lines. In agreement with this, the frequency of GHh increased in sublines
      selected for high 42-day weight and decreased in sublines selected for low 42-day
      weight. The IGF-2H5 allele was associated with higher weights in a sex-dependent
      manner in 5F2. In the high selected subline derived from 5F2, a significant
      increase in the frequency of IGF-2H5 was observed. Therefore this allele, in
      contrast to GHh, appears to be a positive indicator of growth irrespective of
      genetic background.

PMID- 1355457
TI  - Homeotic gene Antennapedia mRNA contains 5'-noncoding sequences that confer
      translational initiation by internal ribosome binding.
AB  - The Antennapedia (Antp) homeotic gene of Drosophila melanogaster has two
      promoters, P1 and P2. The resulting Antp mRNAs contain 1512-nucleotide (P1) and
      1727-nucleotide (P2) 5'-noncoding regions, composed of exons A, B, D, and E (P1)
      or exons C, D, and E (P2), respectively. Multiple AUG codons are present in exons
      A, B, and C. We have found that 252-nucleotide exon D, common to mRNAs from both
      transcription units and devoid of AUG codons, can mediate initiation of
      translation by internal ribosome binding in cultured cells. Many mRNAs in
      Drosophila contain long 5'-noncoding regions with apparently unused AUG codons,
      suggesting that internal ribosome binding may be a common mechanism of
      translational initiation, and possibly its regulation, in Drosophila.

PMID- 1355458
TI  - Concentration-dependent activities of the even-skipped protein in Drosophila
      embryos.
AB  - The Drosophila pair-rule gene even-skipped (eve) encodes a homeo-domain
      containing protein (Eve) that is required for the development of both odd- and
      even-numbered parasegments. We have used a heat shock-inducible eve transgene to
      study the regulatory functions of Eve in vivo. Transcripts encoded by eight other
      segmentation genes were monitored for changes in distribution and abundance
      following short pulses of ectopic Eve expression. Two tiers of response times
      appeared to distinguish between genes that were direct [fushi tarazu (ftz), odd
      skipped (odd), runt (run), paired, and wingless] and indirect [eve, hairy, and
      engrailed (en)] targets of Eve. Genes that appeared to be directly regulated by
      Eve were differentially repressed in a concentration-dependent fashion.
      Interestingly, the run and ftz genes could also be activated by Eve during a
      brief 20- to 30-min stage in development. The delayed actions upon the eve and en
      genes appeared to be mediated by run and odd. As in eve- embryos, these effects
      on segmentation gene expression patterns caused defects in both odd- and even
      numbered parasegments. Four sequential phenotypes could be induced, each of which
      was attributable to the altered expression of a unique subset of target genes.

PMID- 1355459
TI  - Oxygen radicals in ulcerative colitis.
AB  - This article reviews the pathophysiologic concept that superoxide and hydrogen
      peroxide, generated by activated leukocytes, together with low-molecular-weight
      chelate iron derived from fecal sources and from denatured hemoglobin, amplify
      the inflammatory response and subsequent mucosal damage in patients with active
      episodes of ulcerative colitis. The putative pathogenic mechanisms reviewed are
      as follows: (1) Dietary iron is concentrated in fecal material owing to normally
      limited iron absorption. (2) Mucosal bleeding, characteristic of ulcerative
      colitis, as well as supplemental oral iron therapy for chronic anemia, further
      conspire to maintain or elevate mucosal iron concentration in colitis. (3) Fenton
      chemistry, driven especially by leukocyte-generated superoxide and hydrogen
      peroxide, leads to formation of hydroxyl radicals. (4) The resultant oxidative
      stress leads to the extension and propagation of crypt abscesses, either through
      direct membrane disruption by lipid peroxidation or through generation of
      secondary toxic oxidants such as chloramines. (5) Chemotactic products of lipid
      peroxidation, including 4-hydroxynonenal, provide positive feedback to accelerate
      this inflammatory/oxidative process, leading to acute exacerbations of the
      disease. (6) Other oxidized products, such as oxidized tryptophan metabolites,
      created by free radical mechanisms in or near the mucosa, may act as carcinogens
      or tumor promotors that contribute to the exceedingly high incidence of colon
      carcinoma in patients suffering from chronic ulcerative colitis. In this way,
      self-sustaining cycles of oxidant formation may amplify flare-ups of inflammation
      and mucosal injury in ulcerative colitis. This concept, if proved correct by
      subsequent research, would provide a rationale for several novel clinical
      approaches to the management of ulcerative colitis, including use of SOD
      mimetics, iron chelators, and chain-breaking antioxidants.

PMID- 1355460
TI  - [Covering the foot sole and heel with pedicled and free transplants].
AB  - Thirty patients suffering from defects of the weight-bearing areas of the sole
      and heel were analyzed employing various methods. Sensibility was analyzed
      quantitatively. The level of sensibility of the flaps was found to be variable,
      but it had no effect on soft-tissue stability. Sensory recovery in the flaps was
      slow and unpredictable. Gait analysis showed that patients supplied with footwear
      walked relatively symmetrically even though there was a tendency to protect the
      flap by decreased weight-bearing. Postural control as analyzed by a sway plate
      was impaired only in patients with flaps having very poor sensibility. Thin skin
      flaps were found to be most suitable for degloving defects and muscle flaps with
      split-skin coverage for deep defects. The scapular flap was often too thick and
      was prone to develop superficial ulcerations on the weight-bearing areas.

PMID- 1355461
TI  - [Diuretics for cardiovascular therapy rediscovered. Diuretics-Therapeutic
      Perspectives for the 90s. Symposium. Internal Medicine Congress. Wiesbaden, 27
      April 1992].

PMID- 1355462
TI  - Supreme Court rulings in two cases broaden legal protections for mentally ill
      criminal defendants.

PMID- 1355463
TI  - c-erbB-2 oncogene in breast cancer: the right target or a decoy?

PMID- 1355464
TI  - Overexpression of HER-2/neu and its relationship with other prognostic factors
      change during the progression of in situ to invasive breast cancer.
AB  - Using permanent-section immunohistochemistry, we investigated the role of HER
      2/neu in the development and progression of human breast cancer by measuring its
      overexpression in a series of hyperplastic (n = 30), dysplastic (n = 15), and
      malignant neoplastic (n = 708) lesions of ductal epithelium and by evaluating the
      relationships between overexpression and clinicopathologic features known to have
      prognostic significance in these lesions. The neoplasms included pure ductal
      carcinoma in situ (DCIS; n = 59) and infiltrating ductal carcinoma (IDC; n =
      649). The latter were all node negative and stratified into IDC combined (n =
      237) or not combined (n = 412) with a "significant amount" of DCIS (defined as
      DCIS greater than or equal to 10% of total tumor cellularity). Overexpression of
      HER-2/neu was not observed in any of the hyperplastic or dysplastic lesions. In
      contrast, it was present in 56% of pure DCIS and in 77% of the comedo subtype of
      this group. Only 15% of IDC overexpressed HER-2/neu. However, the rate of
      overexpression was significantly higher in the subset of IDC combined with DCIS
      compared with the subset of IDC not combined with DCIS (22% v 11%, respectively;
      P less than .0001). These results are consistent with the hypothesis that HER
      2/neu plays a more important role in initiation than in progression of ductal
      carcinomas. They also suggest that overexpression decreases within individual
      tumors as they evolve from in situ to increasingly invasive lesions or,
      alternatively, that many invasive carcinomas arise de novo (ie, without
      progressing through a significant in situ stage) by mechanisms not involving HER
      2/neu. In addition, overexpression of HER-2/neu was associated with several poor
      prognostic features (younger patient age, premenopause, negative estrogen
      receptor status, negative progesterone receptor status, and high nuclear grade)
      in the subset of IDC combined with DCIS. With one exception (negative estrogen
      receptor status) these associations were lost in IDC not combined with DCIS, also
      suggesting that the role of HER-2/neu changes during the progression of human
      breast cancer.

PMID- 1355466
TI  - Use of gut peptide receptor agonists and antagonists in gastrointestinal
      diseases.
AB  - Because of the numerous actions of gut peptides and the numerous approaches to
      modification of their activity, it is likely that many other agents will be
      introduced in the near future. Although a peptide analogue has so far found the
      largest clinical role, given the problems of peptide pharmacology, the
      development of nonpeptide gut peptide agonists and antagonists has more promise
      of clinical usefulness.

PMID- 1355465
TI  - Control of gastric acid secretion. Histamine H2-receptor antagonists and H+K(+)
      ATPase inhibitors.
AB  - Gastric acid secretion is regulated by an intricate interplay of neural
      (acetylcholine), hormonal (gastrin), and paracrine (histamine, somatostatin)
      mechanisms. Receptors for each of these agents and the signal transduction
      pathways to which these receptors are coupled have been identified on the
      parietal cell. The stimulatory effect of acetylcholine and gastrin is mediated by
      an increase in cytosolic calcium, whereas that of histamine is mediated by
      activation of adenylate cyclase and generation of cAMP. Strong potentiation
      between histamine and either gastrin or acetylcholine reflects postreceptor
      interaction between the distinct pathways as well as the ability of acetylcholine
      and gastrin to release histamine from mucosal ECL cells. The inhibitory effects
      of somatostatin on acid secretion are mediated by receptors coupled by guanine
      nucleotide-binding proteins to inhibition of adenylate cyclase activity. All the
      pathways converge on and modulate the activity of the luminal enzyme, H+K(+)
      ATPase, the proton pump of the parietal cell. Precise information on the
      mechanisms involved in gastric acid secretion has led to the development of
      potent drugs capable of inhibiting acid secretion. These include competitive
      antagonists that interact with stimulatory receptors (e.g., histamine H2-receptor
      antagonists) as well as noncompetitive inhibitors of H+K(+)-ATPase (e.g.,
      omeprazole). The histamine H2-receptor antagonists (cimetidine, ranitidine,
      famotidine, and nizatidine) continue as first-line therapy for peptic ulcer
      disease and are effective in preventing relapse. Although they are generally well
      tolerated, histamine H2-receptor antagonists may cause untoward CNS, cardiac, and
      endocrine effects as well as interference with the absorption, metabolism, and
      elimination of various drugs. Omeprazole is a weak base that reaches the parietal
      cell through the bloodstream, diffuses through the cytoplasm, and becomes
      activated and trapped as a sulfenamide in the acidic canaliculus of the parietal
      cell. It covalently binds to H+K(+)-ATPase, thereby irreversibly blocking acid
      secretion in response to all modes of stimulation. The main drawback to its use
      is its extreme potency, which leads to virtual anacidity, gastrin and ECL cell
      hyperplasia, hypergastrinemia, and, in rats, to the development of carcinoid
      tumors.

PMID- 1355467
TI  - Antiemetics.
AB  - This article explores recent knowledge on the physiology and neuropharmacology of
      the emetic process. It seeks to outline the indications for specific antiemetic
      drugs and where their actions are targeted. Much of the information for the role
      of antiemetic drugs has come from experience with antiemetics in patients
      receiving cytotoxic chemotherapy. The role of the new 5-HT3 receptor antagonists
      is outlined, with special reference to ondansetron.

PMID- 1355468
TI  - Sulfasalazine and 5-ASA compounds.
AB  - New aminosalicylate formulations have recently been introduced for the treatment
      of inflammatory bowel disease. Trials in the past decade have convincingly
      demonstrated their effectiveness in mildly to moderately active ulcerative
      colitis and in relapse prevention. The rate of side effects was significantly
      lower with the new aminosalicylates than with conventional sulfasalazine
      treatment. The therapeutic effects of the new aminosalicylates in Crohn's disease
      have been less pronounced, and their role in this disease requires further
      trials.

PMID- 1355469
TI  - Life stressors and coping style are associated with immune measures in HIV-1
      infection--a preliminary report.
AB  - OBJECTIVE: Life stressors and coping style have been associated with alterations
      in cellular immunity similar to those seen in HIV-1 infection. The interval
      between infection with HIV-1 and the development of AIDS is lengthy and highly
      variable. This pilot study investigated whether life stressors and coping style
      may account for a portion of this variation. METHOD: A sample of eleven
      asymptomatic HIV-1 seropositive homosexual male volunteers responding to a local
      advertisement was assessed on life stressors, coping style and cellular
      phenotypic and functional immune measures--T4 "helper" cell/T8 "suppressor" cell
      ratio, T4 cell count, total lymphocyte count, and natural killer cell
      cytotoxicity. RESULTS: Significant associations were observed for both major life
      stressor impact over the previous year and passive coping style use with the
      total lymphocyte count; higher life stressor impact and passive coping style use
      were associated with lower total lymphocyte counts. Similarly, a trend in the
      same direction was found for the relationship of these two measures with the
      count of T4 cells, which are directly infected and killed by HIV-1. CONCLUSIONS:
      It is well documented that decrements in T4 cell and total lymphocyte counts are
      powerful predictors of subsequent clinical progression to AIDS. These preliminary
      findings suggest that life stressors and coping style may also be predictors of
      the development of AIDS.

PMID- 1355470
TI  - Some effects of vitamin A deficiency on the isolated rat lung alveolar type II
      cell.
AB  - Alveolar Type II cells were isolated from control and vitamin A deficient rats
      and allowed to form a monolayer in plastic dishes for 16-18 hours. The vitamin A
      content (retinol plus retinyl palmitate) of deficient cells was 50-75% less than
      in control cells on a per mg protein basis. Isolated Type II cells took up [3H]
      retinol, synthesized [3H]-retinyl palmitate, and after 4 hours, 24% of the
      radioactivity in the Type II cells was [3H]-retinoic acid. Deficiency did not
      appear to alter retinoic acid synthesis. Phosphatidylcholine (PC) and disaturated
      phosphatidylcholine (DSPC) synthesis, were slightly less in deficient cells
      compared to control (95 and 85% respectively). In addition, 10(-6) M and 10(-5) M
      retinoic acid in the reaction media stimulated both PC and DSPC synthesis by 120
      140% in control cells. The stimulating effect of retinoic acid was present in
      deficient cells as well, but less pronounced (120% with 10(-5) M). Vitamin A
      deficient Type II cells also had less basal levels of both tissue
      transglutaminase and epidermal transglutaminase activity than control cells.

PMID- 1355472
TI  - Benarthin: a new inhibitor of pyroglutamyl peptidase. II. Physico-chemical
      properties and structure determination.
AB  - Benarthin, a new inhibitor of pyroglutamyl peptidase (PG-peptidase), has been
      isolated from the culture broth of Streptomyces xanthophaeus MJ244-SF1. The
      structure of benarthin was determined to be L-(2,3-dihydroxybenzoyl)argininyl-L
      threonine by analysis of spectral properties and through chemical studies.

PMID- 1355473
TI  - Benarthin: a new inhibitor of pyroglutamyl peptidase. III. Synthesis and
      structure-activity relationships.
AB  - Benarthin, a new inhibitor of pyroglutamyl peptidase (PG-peptidase), has been
      isolated from the culture filtrate of Streptomyces xanthophaeus MJ244-SF1. The
      structure of benarthin has been determined to be L-(2,3-dihydroxybenzoyl)arginyl
      L-threonine. This structure was confirmed by the total synthesis of benarthin.
      Moreover, we synthesized benarthin derivatives to obtain information on the
      relationship between structure and inhibitory activity. The results indicated
      that the catechol group of benarthin is the essential moiety for the inhibition
      of PG-peptidase.

PMID- 1355471
TI  - Benarthin: a new inhibitor of pyroglutamyl peptidase. I. Taxonomy, fermentation,
      isolation and biological activities.
AB  - We found benarthin, a new inhibitor of pyroglutamyl peptidase, in the
      fermentation broth of Streptomyces xanthophaeus MJ244-SF1. It was purified by
      column chromatography and centrifugal partition chromatography (CPC) and then was
      isolated as a colorless powder. The binding of benarthin was competitive with
      substrate and its inhibition constant (Ki) was 1.2 x 10(-6) M.

PMID- 1355474
TI  - Synthesis of 1233A analogs and their inhibitory activity against
      hydroxymethylglutaryl coenzyme A synthase.
AB  - Simple and efficient syntheses of 1233A analogs were developed and the inhibitory
      activity of the analogs against hydroxymethylglutaryl coenzyme A (HMG-CoA)
      synthase was determined. Study of the structure-activity relationships revealed
      that not only the geometry in beta-lactone moiety but also the length of the
      carbon side chain is important for inhibitory activity against HMG-CoA synthase.

PMID- 1355475
TI  - Psychophysiologic response during script-driven imagery as an outcome measure in
      posttraumatic stress disorder.
AB  - BACKGROUND: A psychophysiologic method previously validated in Vietnam veterans
      was used to evaluate the responses of medication-free Israeli posttraumatic
      stress disorder (PTSD) patients to script-driven imagery, before and after
      treatment with systematic desensitization. METHOD: Skin conductance, heart rate,
      and frontalis EMG responses during imagery of traumatic events were assessed in
      three unmedicated Israeli PTSD patients. The t test of significance was used to
      compare the magnitude of the response to traumatic imagery with that of responses
      to imagery of nine other events. RESULTS: The elevated physiologic responses to
      traumatic imagery, observed before treatment, normalized after systematic
      desensitization. Imagery of traumata that were not treated by desensitization
      continued to produce elevated responses. CONCLUSION: Physiologic response during
      traumatic imagery may be useful in the evaluation of differential treatment
      outcome in PTSD.

PMID- 1355476
TI  - Chaperonin cpn60 from Escherichia coli protects the mitochondrial enzyme
      rhodanese against heat inactivation and supports folding at elevated
      temperatures.
AB  - The chaperonin protein cpn60 from Escherichia coli protects the monomeric,
      mitochondrial enzyme rhodanese (thiosulfate:cyanide sulfurtransferase, EC
      2.8.1.1) against heat inactivation. The thermal inactivation of rhodanese was
      studied for four different states of the enzyme: native, refolded, bound to cpn60
      in the form of a binary complex formed from unfolded rhodanese, and a thermally
      perturbed state. Thermal stabilization is observed in a range of temperatures
      from 25 to 48 degrees C. Rhodanese that had been inactivated by incubation at 48
      degrees C, in the presence of cpn60 can be reactivated at 25 degrees C, upon
      addition of cpn10, K+, and MgATP. A recovery of about 80% was achieved after 1 h
      of the addition of those components. Thus, the enzyme is protected against heat
      inactivation and kept in a reactivable form if inactivation is attempted using
      the binary complex formed between rhodanese folding intermediate(s) and cpn60.
      The chaperonin-assisted refolding of urea-denatured rhodanese is dependent on the
      temperature of the refolding reaction. However, optimal chaperonin assisted
      refolding of rhodanese observed at 25 degrees C, which is achieved upon addition
      of cpn10 and ATP to the cpn60-rhodanese complex, is independent of the
      temperature of preincubation of the complex, that was formed previously at low
      temperature. The results are in agreement with a model in which the chaperonin
      cpn60 interacts with partly folded intermediates by forming a binary complex
      which is stable to elevated temperatures. In addition, it appears that native
      rhodanese can be thermally perturbed to produce a state different from that
      achieved by denaturation that can interact with cpn60.

PMID- 1355477
TI  - Effects of the chaperonin GroE on the refolding of tryptophanase from Escherichia
      coli. Refolding is enhanced in the presence of ADP.
AB  - The refolding of the tetrameric enzyme tryptophanase was facilitated by the
      chaperonin GroE. Maximum refolding yield of tryptophanase molecules (about 80%)
      was attained in the presence of a 15-fold excess of GroE 21-mer over
      tryptophanase monomer. The GroEL subunit was required for this improvement in
      refolding yield, whereas the GroES subunit was not. Light scattering experiments
      of the refolding reaction revealed that GroE bound to tryptophanase folding
      intermediates and suppressed their aggregation. The presence of ATP was required
      for the efficient dissociation of tryptophanase from GroEL. However, our
      experiments indicated that tryptophanase dissociated readily from GroEL in the
      presence of not only ATP, but also in the presence of non-hydrolyzable ATP
      analogues such as ATP gamma S (adenosine 5'-O-(3-thiotriphosphate)) and AMP-PNP
      (adenyl-5'-yl imidodiphosphate) as well. Surprisingly, the release of
      tryptophanase from GroEL was facilitated in the presence of ADP as well. We
      concluded that the binding of nucleotides such as ATP and ADP changed the
      conformation of GroEL and facilitated the dissociation of tryptophanase
      molecules. The conformation formed in the presence of ADP was distinct from the
      conformation formed in the presence of ATP, as shown by the selective
      dissociation of various folding proteins from the two conformations.

PMID- 1355478
TI  - Serine mutations in transmembrane V of the dopamine D1 receptor affect ligand
      interactions and receptor activation.
AB  - Several serines present in transmembrane domain V are conserved among members of
      the G-protein-coupled receptor family that bind catecholamines. Two of these
      serines that are present in the beta-adrenergic receptor were previously shown by
      site-directed mutagenesis to affect agonist binding and receptor activation
      (Strader, C. D., Candelore, M. R., Hill, W. S., Sigal, I. S., and Dixon, R. A. F.
      (1989) J. Biol. Chem. 264, 13572-13578). We investigated the role of the serines
      present in transmembrane V of another catecholamine receptor, the dopamine D1
      receptor, by site-directed mutagenesis, and the results show that mutations at
      serines 198, 199, and 202 affect dopamine binding. The substitution of serine 198
      or serine 199 by an alanine also affects the binding of several other agonist and
      antagonist dopaminergic compounds while an alanine substitution at serine 202 has
      no effect on the binding of these compounds. Moreover, each single serine
      mutation decreased the maximal cAMP accumulation elicited by a dopamine D1
      partial agonist. These results suggest that serines present in transmembrane V of
      the D1 receptor affect ligand interactions and receptor signal transduction, but
      not entirely in the manner that would be predicted from the model proposed for
      the beta-adrenergic receptor.

PMID- 1355479
TI  - Evidence for inserted sequences in the head region of nonmuscle myosin specific
      to the nervous system. Cloning of the cDNA encoding the myosin heavy chain-B
      isoform of vertebrate nonmuscle myosin.
AB  - The complete amino acid sequence of a vertebrate nonmuscle myosin heavy chain-B
      isoform (MHC-B, 1976 amino acids, 229 kDa) has been deduced by using cDNA clones
      from chicken brain libraries. The chicken nonmuscle MHC-B shows overall
      similarity in primary structure to other MHCs in the areas contributing to the
      ATP-binding site and actin-binding site. Similar to other nonsarcomeric MHC IIs,
      there is a short uncoiled tail sequence at the carboxyl terminus of the molecule.
      It is in the uncoiled tail sequence that the greatest number of differences in
      amino acids sequence between MHC-A and B were found, which allowed generation of
      isoform-specific antibodies. These antibodies were used to determine the relative
      content of MHC-A and MHC-B in various tissues. During the cloning of the cDNA
      encoding chicken brain MHC-B, we found a 63-nucleotide insertion encoding 21
      amino acids located in the head region of the MHC near to the actin-binding site
      and a 30 nucleotide insertion encoding 10 amino acids near to the ATP-binding
      site. Analysis using S-1 nuclease showed that both inserts are expressed in a
      tissue-dependent manner; mRNA containing the inserts is present in tissues of the
      nervous system, but is absent from other non-muscle cells, which contain the
      noninserted isoform of MHC-B. Similar inserts were found in corresponding
      positions in human cerebellar mRNA. Antibodies raised against a peptide
      synthesized based on the 21 amino acid insert found in chickens recognize a MHC
      isoform in the same tissues that are enriched for the mRNA. These insertions
      appear to be a mechanism for generating additional MHC-B isoforms specific to the
      nervous system.

PMID- 1355480
TI  - The human loricrin gene.
AB  - Loricrin is the major protein component of the cornified cell envelope of
      terminally differentiated mammalian epidermal (stratum corneum) cells. Using a
      specific human cDNA clone, we have isolated and characterized the human loricrin
      gene. We show that it has a very simple structure of a single intron of 1188 base
      pairs (bp) in the 5'-untranslated region; there are no introns in coding
      sequences. By use of rodent-human somatic cell hybrids, followed by in situ
      hybridization with a biotin-labeled genomic DNA clone, the single-copy gene maps
      to chromosome location 1q21. Polymerase chain reaction analyses of genomic DNAs
      from different individuals show that human loricrin consists of two allelic size
      variants, due to sequence variations in its second glycine loop domain, and these
      variants segregate in the human population by normal Mendelian mechanisms.
      Furthermore, there are multiple sequence variants within these two size class
      alleles due to various deletions of 12 bp (4 amino acids) in the major loop of
      this glycine loop domain. By use of a specific loricrin antibody, we show by
      immunogold electron microscopy that loricrin initially appears in the granular
      layer of human epidermis and forms composite keratohyalin granules with
      profilaggrin, but localizes to the cell periphery (cell envelope) of fully
      differentiated stratum corneum cells.

PMID- 1355481
TI  - Properties of a HeLa cell 3' exonuclease specific for degrading poly(A) tails of
      mammalian mRNA.
AB  - A HeLa cell 3'-exonuclease with properties of a mammalian mRNA poly(A) tail
      removing enzyme has been characterized. The exonuclease shows high specificity
      for the poly(A) tail, and it is single strand-specific and requires a 3'-hydroxyl
      group for its activity. During degradation 5'-AMP is liberated as a product, and
      a 3'-OH group is left on the last adenosine residue of the remaining poly(A)
      tail. The activity is inhibited by 5'-AMP and can be competed by poly(A)
      containing mRNA or poly(A). Based on these findings we propose a reaction pathway
      for poly(A) tail removal catalyzed by the HeLa cell poly(A) tail-specific 3'
      exonuclease.

PMID- 1355482
TI  - Interactions of the heme-regulated eIF-2 alpha kinase with heat shock proteins in
      rabbit reticulocyte lysates.
AB  - Inhibition of protein synthesis in rabbit reticulocyte lysates occurs in response
      to a variety of conditions including heme deficiency, addition of oxidants, and
      heat stress. The inhibition of translation is due to the activation of a heme
      regulated protein kinase (HRI) which specifically phosphorylates the alpha
      subunit of the eukaryotic initiation factor eIF-2. In this report,
      immunoadsorption with monoclonal antibodies (mAbs) and Western blot analysis were
      used to investigate the interaction of HRI, the 90-kDa heat shock protein (hsp
      90), hsp 70, and the EC1 antigen in rabbit reticulocyte lysates under protein
      synthesizing conditions. The data indicate that hsp 90, hsp 70, and the EC1
      antigen interact with HRI in rabbit reticulocyte lysate. The EC1 antigen is a
      protein that has been demonstrated to be associated with several steroid hormone
      receptor-hsp 90 complexes and reacts with the KN 382/EC1 mAb (EC1). The
      association of HRI with hsp 90 and the EC1 antigen in the reticulocyte lysate was
      found to be dependent on the presence of hemin at a concentration of 5 microM or
      higher; little HRI was coadsorbed by the 8D3 anti-hsp 90 mAb or the EC1 mAb in
      the absence of hemin. Hsp 70 remains associated with HRI in the absence of hemin,
      suggesting that hsp 90 and 70 may bind to HRI at different sites. The
      immunological properties of the hsp 70 associated with HRI indicate that it may
      be the constitutively express heat shock cognate protein (hsc 73). The results
      suggest that the association of HRI with hsp 90 and the EC1 antigen may be in a
      dynamic equilibrium, in which complex formation is either facilitated or
      stabilized by the presence of hemin, and supports the notion that these proteins
      in conjunction with hsp 70 may play a role in regulating HRI activity or
      activation in situ.

PMID- 1355483
TI  - Flow cytometric analysis of multidrug-resistance-associated antigen (P
      glycoprotein) and DNA ploidy in human colon cancer.
AB  - In many cell systems, resistance to cytotoxic drugs is acquired by the
      amplification and/or overexpression of the multidrug resistance (mdr) gene, which
      codes for the glycoprotein, p170 (P-glycoprotein). Moreover, in a variety of
      malignant tumours there is increasing evidence of the relationship between the
      DNA ploidy pattern of patients and their prognosis. In this study we aimed to
      evaluate these two potential indicators of constitutive drug resistance in human
      colorectal tumours. We employed a method to quantify simultaneously, on a per
      cell basis, mdr gene expression (using the C219 monoclonal antibody for P
      glycoprotein) and nuclear DNA content with high-resolution bivariate flow
      cytometry. The study was performed on a human colon-carcinoma-derived cell line
      (LoVo) and its doxorubicin-resistant variant (LoVo/Dx) and on tumour samples and
      adjacent normal mucosa from 35 untreated patients with colon cancer. The P
      glycoprotein was found in both LoVo and LoVo/Dx cells with levels slightly lower
      in the parental than in the resistant subline (P, NS). A multi-drug-resistant
      specific probe for mRNA expression and Western blot assay confirmed the
      specificity of p170 expression. All of the colon cancer with unimodal diploid DNA
      distribution and all the normal colonic mucosa samples showed P-glycoprotein
      expression, without a statistically significant difference in median values
      between tumours and normal samples. Tumours with bimodal DNA distribution showed
      median values of P-glycoprotein expression of their hyperdiploid cell clones
      significantly higher than those of their diploid clones and of the tumours with
      unimodal DNA distribution (P less than 0.005). Our results show the feasibility
      of bivariate flow-cytometric analysis of P-glycoprotein expression and DNA
      content on clinical material and support the hypothesis that the MDR phenotype
      and DNA ploidy together may influence the biological behaviour of colon cancer in
      vivo.

PMID- 1355484
TI  - Expression of intercellular adhesion molecule 1 (ICAM-1) during the development
      of invasion and/or metastasis of gastric carcinoma.
AB  - In this study, using two-color flow-cytometric analysis, we examined the
      expression of histocompatibility locus antigens (HLA) classes I and II, and
      intercellular adhesion molecule 1 (ICAM-1) in 10 cases of normal gastric mucosa,
      13 cases of primary carcinoma on the stomach, 16 cases of metastatic carcinoma
      from malignant ascites in patients with gastric carcinoma and 14 samples of their
      cultured carcinoma cells. Compared with normal gastric mucosa, HLA class I were
      highly expressed in a considerable number of tumor cells in each experimental
      group. The expression of HLA class II tended to reduce in the order of normal
      gastric mucosa, primary gastric carcinoma and peritoneal-effusion-associated
      carcinoma. Altogether, 85.7% of cases of cultured tumor cells showed abrogation
      and loss of HLA class II. The ICAM-1 molecule was not detected on normal gastric
      epithelial cells. In few cases, carcinoma cells from large volumes of tumor
      located in the stomach showed detectable amounts of ICAM-1. On the other hand,
      all of the metastatic carcinoma cells from peritoneal effusions showed a high
      level of expression of the ICAM-1 molecule. The expression of ICAM-1 on
      adenocarcinoma cells was maintained and/or augmented by in vitro cultivation with
      tumor-infiltrating lymphocytes (TIL). Furthermore, two-color fluorescence
      activated cell sorting analysis of TIL revealed that significant correlation was
      observed between the expression of ICAM-1 and the degree of TIL, composed mainly
      of CD3+ T cells including CD8+CD11b-, CD8+CD28+, CD8+S6F1+ and CD4+Leu8+, and
      CD57+CD16- and CD57+CD16+ NK cells, and HLA-DR+LeuM3+ macrophages.

PMID- 1355486
TI  - Evaluation of different staging systems for Kaposi's sarcoma in HIV-infected
      patients.
AB  - The records of 49 consecutive AIDS patients with Kaposi's sarcoma were analysed
      retrospectively to assess the prognostic value of the four staging systems
      proposed for epidemic Kaposi's sarcoma. The classifications by Krigel and
      Mitsuyasu do not describe exactly the characteristics of the disease, and do not
      give enough information on survival. Our study confirms that CD4+ cell depletion,
      systemic symptoms and opportunistic infections at diagnosis are the major
      prognostic factors and influence survival to a great extent, as shown by Krown
      and Chachoua.

PMID- 1355485
TI  - Relationship of CD15 immunoreactivity and prognosis in sporadic medullary thyroid
      carcinoma.
AB  - Immunoreactivity with monoclonal antibody CD15 (Leu-M1) was investigated in the
      primary tumours, the metastases and local recurrences of 47 cases of sporadic
      medullary carcinoma of the thyroid (MTC). Of these tumours, 36.5% showed a
      varying degree of CD15 immunostaining; in 7 carcinomas the CD15 immunoreactivity
      was found to be significant (greater than 15% tumour cells positively stained).
      Staining of the amyloid stroma was observed in 3 tumours. Significantly higher
      epithelial CD15 positivity was seen more frequently in the group with larger
      tumours (greater than 4 cm) and was found exclusively in the presence of lymph
      node metastases. No substantial difference in the percentage of immunostained
      cells was seen between primary tumours and metastatic or recurrent lesions,
      except for two cases that revealed a significant increase in the number of CD15
      immunostained cells in metastatic and recurrent lesions. Five of 7 patients with
      recurrences showing significant CD15 immunostaining died of cancer, while in the
      absence of significant CD15 staining all patients with recurrences were still
      alive at the conclusion of the study. The prognostic value of CD15
      immunoreactivity, found by univariate analysis, becomes weaker after adjustment
      for the size and stage of tumour. Particularly in patients with tumour
      recurrences CD15 immunostaining may be of clinical relevance for the selection of
      patients in whom a more radical surgical approach would be justified.

PMID- 1355488
TI  - 9th International Symposium on Affinity Chromatography and Biological
      Recognition. Yokohama, September 24-28, 1991.

PMID- 1355487
TI  - Simultaneous high-performance liquid chromatographic analysis of buspirone and
      its metabolite 1-(2-pyrimidinyl)-piperazine in plasma using electrochemical
      detection.
AB  - A selective and sensitive high-performance liquid chromatographic method with
      coulometric detection is described for the quantitation of buspirone and its
      active metabolite, 1-(2-pyrimidinyl)piperazine, in plasma samples of mice treated
      orally with buspirone (10 mg/kg body weight). The analytes are extracted with a
      carboxylic acid solid-phase extraction column before chromatography. A dual
      electrode electrochemical detector is used. The limit of detection is 50 pg for
      buspirone and 35 pg for 1-(2-pyrimidinyl)piperazine.

PMID- 1355489
TI  - Dopaminergic stimulation of oxytocin concentrations in the plasma of male and
      female monkeys by apomorphine and a D2 receptor agonist.
AB  - Administration of the dopamine receptor agonist apomorphine causes a dose
      dependent increase in plasma oxytocin concentrations and dose-specific behavioral
      changes in rodents. To investigate whether dopamine receptor agonists will elicit
      similar neuroendocrine and behavioral effects in primates, we administered graded
      doses of apomorphine and the respective dopamine D1 and D2 receptor agonists, CY
      208-243 and LY 163502, to monkeys and monitored plasma concentrations of oxytocin
      and behavior. Five female rhesus, two male rhesus, and two male cynomolgus
      monkeys had chronic indwelling venous catheters implanted and were maintained on
      standard jacket/tether/swivel systems to allow remote blood sample collection.
      During experiments, blood samples were collected 10 and 5 min before drug
      injection and at 2- to 120-min intervals after each injection. Apomorphine (50
      400 micrograms/kg) and LY 163502 (10-100 micrograms/kg) elicited dose-dependent
      stimulations of oxytocin secretion. CY 208-243 (100-400 micrograms/kg) did not
      significantly affect oxytocin secretion. Low doses of apomorphine (50-100
      micrograms/kg) and LY 163502 (10-25 micrograms/kg) elicited yawning, and high
      doses of apomorphine (200-400 micrograms/kg) and LY 163502 (50-100 micrograms/kg)
      elicited stereotypic behaviors. No behavioral effects of CY 208-243 (100-400
      micrograms/kg) were observed. The magnitude of the oxytocin secretory responses
      varied among animals, but was similar in male and female monkeys. In summary,
      apomorphine and LY 163502 both elicited dose-related stimulation of oxytocin
      secretion coupled with dose-specific behavioral changes in male and female
      monkeys, while no effects of CY 208-243 on these parameters were observed. We
      conclude that dopamine receptor agonists, and in particular D2 agonists, may be
      useful tools for studies exploring the physiological and behavioral actions of
      oxytocin in primates.

PMID- 1355490
TI  - Is Far a Hox mutation?
AB  - The mouse First arch mutation, Far, causes a severe syndrome of craniofacial
      defects described previously. All of the known defects are derived from the
      anterior first arch, and to a very small extent, the dorsal second arch. Recently
      Far has been shown to be closely linked to Ulnaless on chromosome 2, and
      therefore in the vicinity of the Hox-4 gene cluster. This paper reports the
      results of several studies focused on the development origin of the most
      consistently expressed dominant effect caused by Far, an abnormal major
      bifurcation of the maxillary nerve. Nerve-stained whole-mount preparations of day
      12 embryos showed that in Far mutants the maxillary nerve appears to have a
      central wedge missing from the normal single-stalked fan shape, and that the
      nerve defect in Far/Far and +/Far may be equally severe. The effect of retinoic
      acid on the development of the maxillary nerve was tested. Maternal treatment
      with 5 mg/kg retinoic acid on day 9 of gestation had no detectable effect on the
      maxillary nerve of +/Far embryos, and similar treatment with a teratogenic dosage
      (20 mg/kg) on day 8 or 9 produced no Far-like maxillary nerve defects in
      genetically normal embryos. The neural crest cells that give rise to nerves and
      mesenchyme of the first arch originate from specific rhombomeres, discrete
      segments of the developing head. The rhombomeres of 15 embryos at the 14-23
      somite stages, of which 75% are expected to be +/Far or Far/Far, were examined.
      There was no detectable defect in segmentation or morphology of the rhombomeres
      compared with controls. The significance of ectopic cartilage in the palate of
      Far/Far mutants in relation to nerve bifurcation was explored. In histological
      studies, five out of six Far/Far day-15 fetuses had a rod of ectopic cartilage
      lateral to the posterior palate, running parallel to, and morphologically similar
      to, Meckel's cartilage, and lying between the two trunks of the abnormally
      bifurcated maxillary nerve. None of six +/Far day-15 fetuses examined had
      detectable ectopic cartilage in this region. We hypothesize that the maxillary
      nerve defects in Far mutants may be explained by the presence of an ectopic
      precartilaginous blastema that does not always further develop into detectable
      cartilage. The ectopic cartilage found in Far/Far resembles the epibranchial
      cartilage expressed in more posterior branchial arches and in the first arch of
      lower organisms, and therefore may represent an atavistic posteriorization of the
      anterior first arch in Far mutants.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1355491
TI  - Neurological consequences of immune dysfunction: lessons from HIV infection and
      multiple sclerosis.
AB  - In a recent workshop held on Sanibel Island, Florida (18-21 January 1992), the
      two most common neuroimmunologic diseases of young adults, multiple sclerosis
      (MS) and HIV encephalopathy, were jointly discussed. The logic of assembling
      investigators from these two fields was based not on an assumed etiologic
      connection between MS and retroviral infection of the central nervous system
      (CNS), but rather in the hope of uncovering potential common pathogenic
      mechanisms, particularly as might relate to trafficking of mononuclear cells into
      the central nervous system, the distribution and function of macrophages and
      microglia, the structure and function of the blood-brain barrier, and the role of
      cytokines released by activated cells. Multiple sclerosis is a disease without a
      known etiologic agent or pathogenesis. While the causative agent for HIV
      leukoencephalopathy is known, the pathogenesis of the disease remains entirely
      enigmatic (a topic covered by R. Johnson). This meeting brought together two
      different groups of investigators to compare and contrast the diseases and to
      share perspectives, paradigms, and data with the aim of cross-fertilizing the
      disciplines and generating healthy hybrids.

PMID- 1355492
TI  - MMPI interpretation of psychiatric inpatients: caution in making inferences about
      concentration and memory.
AB  - The relation of specific MMPI scores to attention, concentration, and memory was
      assessed in an inpatient psychiatric sample diagnosed by DSM-III-R criteria as
      having schizophrenia, chronic undifferentiated type (n = 22); schizophrenia,
      paranoid type (n = 17); and schizoaffective disorder (n = 20). MMPI indices that
      are used widely to infer cognitive efficiency--including Scales 2 (Depression), 8
      (Schizophrenia), SC-PT, D4 (Mental Dullness), SC2A (Lack of Ego Mastery,
      Cognitive), PSY (Psychoticism) and ORG (Organic Symptoms)--were investigated in
      relation to actual performance on Digit Span and subtests of the Wechsler Memory
      Scale (WMS, Russell's Revision). Weak correlations emerged (maximum r = .31, p
      less than .05), which suggests that scores on these MMPI measures may not provide
      a reliable basis for inferring attention and memory functioning.

PMID- 1355493
TI  - Comparison of proliferation rates assessed using "multiblock" and conventional
      tissue blocks of lung carcinoma.
AB  - AIMS: To compare the proliferative rates, assessed immunohistochemically, of
      human lung tumours using conventional paraffin wax blocks and the multitumour
      tissue block (MTTB) technique. METHODS: A multiblock containing 20 lung tumours
      (eight adenocarcinomas, five squamous cell, five small cell and two carcinoid
      tumours) was constructed. Sections were also cut from the original blocks of
      formalin fixed, paraffin wax embedded tissue used to construct the multiblock.
      Sections were stained with the monoclonal antibody PC10, which recognises a
      proliferating cell nuclear antigen, using the three stage immunoperoxidase
      technique. RESULTS: The proliferation rates of the lung tumours obtained using
      both techniques were, overall, significantly different (p = 0.05), although most
      cases showed good correlation. Some tumours displayed a high degree of
      intratumoral variation in PC10 staining. The degree of PC10 staining was in
      keeping with the known proliferative state of particular histological subtypes-
      that is, carcinoid tumours showed little staining and small cell carcinomas
      showed extensive positivity. CONCLUSION: The MTTB technique is a less suitable
      means of assessing proliferation rate in lung carcinomas than conventional tissue
      blocks. It should be restricted to qualitative antibody studies or quantitative
      studies using tumours with little intratumoral variation.

PMID- 1355494
TI  - p53 protein expression in central nervous system neoplasms.
AB  - AIMS: To demonstrate, immunohistochemically, p53 protein expression in a
      selection of central nervous system tumours; to investigate the relation between
      p53 expression and that of the proliferation related antigen, PCNA. METHODS:
      Surgical specimens from 86 central nervous system tumours were routinely fixed,
      paraffin wax embedded, and immunostained with a monoclonal (PAb 1801) and a
      policlonal antibody (CM1) p53 protein and a monoclonal antibody against PCNA
      (PC10). Normal brain samples obtained at necropsy and 10 surgically obtained
      samples of gliotic brain parenchyma were also immunostained. RESULTS: p53 protein
      expression was observed in 35 of 86 brain tumours, suggesting frequent p53 gene
      mutation. p53 protein alterations were associated with all grades of malignancy
      in tumours displaying solely astrocytic differentiation, with the exception of
      pilocytic astrocytomas. In those showing oligodendroglial or ependymal
      differentiation they appeared to be restricted almost to only high grade lesions.
      No p53 immunoreactivity was observed in normal or gliotic brain tissue; p53
      altered expression was not related to the percentage of PCNA labelled cells.
      CONCLUSIONS: The use of sophisticated gene amplification techniques or highly
      sensitive immunohistochemical methods might be useful in distinguishing between
      reactive and neoplastic astrocytic lesions, and in the identification of
      malignant progression in other non-astrocytic glial tumours. Tumours with very
      similar histogenetic differentiation features might actually be a genetically
      heterogeneous group with possible different clinical courses.

PMID- 1355495
TI  - Prognostic value of c-erbB-2 expression in uterine cervical carcinoma.
AB  - AIMS: To study the pattern of expression and prognostic importance of c-erbB-2
      protein in cervical carcinoma. METHODS: Sixty two cases of stage IB/IIA cervical
      carcinoma, representing the three main tumour types, were investigated
      immunohistochemically for the presence of c-erbB-2 protein expression, using a
      monoclonal antibody (CB11) to its internal domain. Follow up of at least five
      years' duration was available in all cases. RESULTS: Definite membrane staining
      was seen in 38.7% of cases. There was a strong correlation with poor survival (p
      less than 0.0001) particularly. For those with adenocarcinomas, this was the case
      when nodal metastases were present. In contrast, for squamous carcinomas and
      adenosquamous carcinomas, the association with a poor prognosis was most apparent
      in those patients without lymph node metastases. CONCLUSIONS: These findings
      raise the possibility that immunostaining for c-erbB-2 protein could be used as a
      prognostic marker and may help identify those patients for whom early adjuvant
      treatment might be beneficial.

PMID- 1355496
TI  - Cathepsin B/L-, elastase-, tryptase-, trypsin- and dipeptidyl peptidase IV-like
      activities in gingival crevicular fluid. A comparison of levels before and after
      basic periodontal treatment of chronic periodontitis patients.
AB  - 20 chronic periodontitis patients were given a full periodontal examination,
      including measurements of probing depth, clinical attachment loss, gingival
      index, bleeding index and plaque index. At a second visit, gingival crevicular
      fluid (GCF) was collected from the deepest accessible probing site of each tooth.
      The patients then received scaling, root planing and other appropriate
      nonsurgical treatment. GCF was collected from the same sites as sampled
      pretreatment and clinical parameters were measured again. Cathepsin B/L-,
      elastase-, tryptase-, trypsin-, and dipeptidyl peptidase IV-like activities in
      GCF samples were determined by fluorimetric assay with peptidyl derivatives of 7
      amino-4-trifluoromethyl coumarin. Following treatment, there were reductions in
      all clinical parameters and all protease activities. Most were statistically
      significant both on a patient level using average patient values and on a site
      level using either individual patient or pooled patient data. As in previous pre
      treatment comparisons, post-treatment protease levels correlated positively and
      significantly with the corresponding clinical parameters at patient and site
      levels. The reductions and correlations were more marked for total enzyme
      activities than concentrations. GCF protease levels appear to reflect the
      clinical status of periodontal lesions and may thus be of value in monitoring
      disease activity.

PMID- 1355497
TI  - Somatostatin- and neuropeptide Y-like immunoreactivity in the dentate area,
      hippocampus, and subiculum of the domestic pig.
AB  - With the principal aim of providing baseline observations for future experimental
      studies, the distribution of somatostatin-like and neuropeptide Y-like
      immunoreactivities is described in the dentate area, hippocampus, and subiculum
      of the domestic pig (Sus scrofa domesticus) and compared with the distribution
      described in other mammals. Intensely stained somatostatin-like immunoreactive
      nerve cell bodies were present throughout the region, with highest densities in
      the dentate hilus, stratum radiatum and stratum oriens of the hippocampal regio
      inferior, stratum oriens of the hippocampal regio superior, and in the subicular
      cell layer. Somatostatin-like immunoreactive terminals were represented by both
      stained fibers and stained puncta. Scattered somatostatin-like immunoreactive
      nerve fibers were seen in most areas, but regular fiber plexuses were present in
      the dentate molecular layer and dentate hilus, stratum moleculare of the
      hippocampus, and in the subicular plexiform layer. Somatostatin-like
      immunoreactive puncta were seen in the dentate molecular layer, stratum
      moleculare of the hippocampus, and in the subicular plexiform layer. Neuropeptide
      Y-like immunoreactive nerve cell bodies were less numerous than somatostatin-like
      immunoreactive ones. They were mainly seen in the dentate granule cell layer and
      dentate hilus, stratum radiatum and stratum oriens of the hippocampus, and in the
      subicular cell layer. Intensely stained neuropeptide Y-like immunoreactive fibers
      were numerous, and present in all areas examined. They formed fiber plexuses in
      the dentate molecular layer and dentate hilus, stratum moleculare of the
      hippocampal regio superior, and in the subicular plexiform layer. Neuropeptide Y
      like immunoreactive puncta were present in the dentate molecular layer, stratum
      moleculare of the hippocampus, and in the subicular plexiform layer. Consistent
      and very characteristic variation in the distribution of somatostatin-like and
      neuropeptide Y-like immunoreactivity was found along the septotemporal axis of
      the hippocampus. The distribution of somatostatin-like and neuropeptide Y-like
      neurons and terminals in the domestic pig displayed striking similarities with
      the basic pattern of organization of these neuropeptides in other species,
      although more subtle species-specific characteristics were also observed in the
      pig.

PMID- 1355499
TI  - Fluvoxamine in the treatment of obsessive compulsive disorder.
AB  - Obsessive compulsive disorder is a chronic, often severe condition that is
      associated with considerable long term morbidity and suffering. Potent serotonin
      reuptake inhibitors are now regarded as first line treatments and their efficacy
      has been established in a series of placebo-controlled studies. The first of
      these compounds to become available, clomipramine, has undesirable effects on a
      number of other receptor systems and is associated with marked anticholinergic
      side effects. Of the selective serotonin reuptake inhibitors fluvoxamine is the
      most widely studied, with three small positive placebo-controlled and two recent
      large multicentre studies. These two studies show that fluvoxamine is associated
      with significant improvement on the Yale-Brown Obsessive Compulsive Scale (Y
      BOCS), the National Institute of Mental Health Obsessive Compulsive Scale (NIMH
      OC) and the Global Improvement item of the Clinical Global Impression (CGImp)
      Scale, compared with placebo.

PMID- 1355498
TI  - Obsessive compulsive disorder. Papers presented at the Obsessive Compulsive
      Symposia held in Florence, June 1991 and Monte-Carlo, October 1991.

PMID- 1355500
TI  - Human resting B lymphocytes can serve as accessory cells for anti-CD2-induced T
      cell activation.
AB  - Although resting B cells are poor accessory cells for signals transmitted through
      the TCR/CD3 complex, we report that these B cells can support T cell
      proliferation when T cell activating signals are delivered through CD2. This was
      first suggested when leucine methyl ester treatment of PBMC abolished
      proliferation induced by anti-CD3, but not by the accessory cell-dependent anti
      CD2 mAb combination, GT2 and OKT11. Then we demonstrated that unstimulated,
      resting B cells could support the proliferation of both CD4+ and CD8+ T cells.
      Aggregated IgG inhibited proliferation, suggesting that anti-CD2 mAb bound to T
      cells were cross-linked by attachment to B cell FcR. Two lines of evidence
      suggested that lymphocyte function-associated Ag-1/intercellular adhesion
      molecule-1 interaction was crucial for anti-CD2-induced proliferation. First,
      proliferation was blocked by mAb against these adhesion molecules. Second,
      intercellular adhesion molecule-1 expression rapidly increased on resting B cells
      after the addition of anti-CD2, but not anti-CD3. This was of interest because
      fixed monocytes, but not fixed B cells, were able to support the proliferative
      response. In contrast to lymphocyte function-associated Ag-1/intercellular
      adhesion molecule-1, CD28/B7 interaction was not required for anti-CD2-induced
      proliferation, although ligation of these molecules provided important
      costimulatory signals for stimulation by anti-CD3. Finally, neutralizing
      antibodies against IL-1 alpha, IL-1 beta, and IL-6 showed only modest inhibitory
      effects on T cell proliferation. The addition of IL-1 and/or IL-6 to T cells
      failed to substitute for accessory cells and were only partially effective with
      fixed B cells. Further evidence of a linkage between CD2 and CD45 isoforms was
      obtained. Anti-CD45RA, but not anti-CD45RO, potentiated anti-CD2-induced T cell
      proliferation. These studies have revealed a novel role for resting B cells as
      accessory cells and have documented costimulatory signals that are important for
      this effect. Because Ag-presentation by resting B cells to T cells generally
      leads to T cell nonresponsiveness, it is possible that this tolerogenic signal
      may be converted to an activation signal if there is concurrent perturbation of
      CD2 on T cells.

PMID- 1355501
TI  - T cell-induced allotypic suppression. Origin of the CD8+ T cells maintaining
      IgG2ab suppression.
AB  - One of the problems raised by the T cell-induced allotypic suppression is the
      origin (donor or host) of the T cells responsible for the chronicity of the
      suppression. To address this point, we used T cells from Igha/a Thy-1.2 mice
      whose natural T cell activity against IgG2ab was enhanced in vivo. These T cells
      were injected into newborn Ighb/b Thy-1.1 mice where they induced complete
      suppression of IgG2ab expression in around 70% of these recipients. During a
      study that lasted more than 1 yr, we found that about 3% of the recipient
      splenocytes were T cells of the donor type. By means of suppression-transfer
      experiments, using either Thy-1.2+ or Thy-1.1+ cell-depleted splenocytes from
      mice suppressed in this manner we were able to unambiguously show that Thy-1.2+
      cell-depleted splenocytes were incapable of transferring the suppression, whereas
      Thy-1.1+ cell-depleted splenocytes could. We thus demonstrated that suppression
      was maintained throughout the recipient's life by donor Thy-1.2+ T cells.

PMID- 1355502
TI  - The cytotoxic process of CD4 Th1 clones.
AB  - Previous studies have demonstrated that murine CD4 Th1 cells lack perforin and
      use a pathway distinctive from CD8 CTL to express cytotoxicity. Whether the
      cytotoxic process of Th1 cells can be separated into identifiable stages and how
      these differences affect this process were determined in this study. We have
      resolved the cytotoxic process of Th1 clones into three stages identical with
      those of CD8 CTL, namely, conjugate formation/activation, lethal hit, and
      effector-independent programming for target DNA fragmentation. By comparing the
      cytotoxic processes between Th1 clones on Ag-pulsed targets and (PMA+A23187)
      activated Th1 clones on unpulsed targets, we have also demonstrated that 1) the
      requirement of CD4 Th1 cells for de novo synthesis of cytotoxic machinery was
      partly responsible for the lag time in the induction of target DNA fragmentation
      by Th1 clones; 2) lethal hit was delivered rapidly; 3) lethal hit under forced
      contact by centrifugation did not need extracellular Ca2+ and Mg2+; 4) without
      centrifugation, lethal hit required extracellular Mg2+, but not Ca2+; 5) the
      average functional half life of the cytotoxic machinery was 54 +/- 24 (n = 4)
      min. The data demonstrate that the cytotoxic process of Th1 clones uses an
      activation-dependent cytotoxic machinery to deliver a short-lived, short-ranged,
      and quick-acting lethal hit to target, which induces a program in target for DNA
      fragmentation.

PMID- 1355503
TI  - Induction and function of eosinophil intercellular adhesion molecule-1 and HLA
      DR.
AB  - We have previously established that eosinophils studied ex vivo from the sputum
      of asthmatics express intercellular adhesion molecule-1 (ICAM-1) and HLA-DR,
      whereas peripheral blood eosinophils do not express these surface proteins. On
      incubation of highly purified (greater than 99.5% pure) blood eosinophils from
      normal subjects with T cell supernatants, eosinophil ICAM-1 was induced in 24 h,
      whereas HLA-DR was maximally induced within 48 h. Recombinant cytokines that
      enable eosinophil survival (IL-5, IL-3, and granulocyte macrophage-CSF) were
      found to be unable to induce ICAM-1 or HLA-DR, even when pooled at concentrations
      individually required for eosinophil survival. However, synergy between these
      eosinophil survival factors and TNF (-alpha and -beta) was found mainly
      responsible for ICAM-1 induction, whereas synergy between IL-3 and IFN-gamma
      occurred for HLA-DR induction. Culture of eosinophils in the presence of
      cytokines and cycloheximide prevented expression of ICAM-1 and HLA-DR, showing
      that de novo eosinophil protein synthesis is occurring. At a functional level we
      demonstrate that ICAM-1-bearing eosinophils have increased adhesion capacity for
      autologous T cells. In contrast, HLA-DR-expressing eosinophils mediated Ag
      specific proliferation of an autologous HLA-DR-restricted T cell clone that was
      inhibitable by anti-HLA-DR and anti-ICAM-1 mAb. Since eosinophil-mediated Ag
      presentation was inhibitable by treatment of eosinophils with glutaraldehyde or
      chloroquine, this suggests that eosinophils participate in Ag uptake, processing,
      and presentation and have accessory functions. Thus, through the induction of
      ICAM-1 and HLA-DR on tissue eosinophils, eosinophils have the capacity to
      interact with leukocytes and present Ag to T cells.

PMID- 1355504
TI  - Absence of T cell tolerance to pancreatic islet cells.
AB  - To examine whether the lack of self-tolerance to beta cells is responsible for
      the development of type I diabetes in nonobese diabetic (NOD) mice, we attempted
      to induce T cell responses to cells from the islets of Langerhans. The data show
      that all NOD mice, irrespective of age, sex, and disease progression, possess
      islet cell-specific CD4+, MHC class II-restricted T cells. Both primary and
      secondary proliferative responses to islet cells were readily induced. The
      activation of T cells required presentation of islet cell Ag by APC in the
      responding lymph node cell population. Cells from other tissues, e.g., salivary
      gland, adrenal gland, and spleen, failed to activate autologous T lymphocytes. T
      cells specific for other Ag did not respond to islet cells, indicating that the
      proliferation is not the result of nonspecific stimulation by islet cell
      products. The presence of islet cell-reactive T cells is, however, not unique to
      NOD mice, because similar T cell reactivity was also demonstrated in non-diabetes
      prone mouse strains. Hence, self-tolerance to islet cells appears to be absent.
      The results indicate a normal occurrence of islet cell-reactive T cells in both
      diabetes-prone as well as non-diabetes-prone mice. Thus, the lack of tolerance
      cannot be the initial cause of diabetes, but the activation of such autoreactive
      T cells may be important for the development of the disease.

PMID- 1355505
TI  - Dissociation of a model DNA compound dApdA by monochromatic soft X-rays in solids
      and comments on the high selectivity for 3' breakage in the phosphoester bond.
AB  - The dissociation products of dApdA (2'-deoxyadenylyl-(3'-5')-2'-deoxyadenosine)
      irradiated in the solid state by highly monochromatic soft X-rays (energy
      resolution, less than 10(-3) near the K-edge of phosphorus were analysed using
      thin-layer chromatography. The major chemical species identified were adenine
      base and 5'-dAMP in approximately equal amounts, indicating that the dissociation
      occurred between the 3' carbon (C3') of deoxypentose and its adjacent phosphorus
      over the energy range of 2.147-2.167 keV, including the K-edge resonance
      absorption of phosphorus at 2.153 keV. In conjunction with the accumulated data
      on the degradation of dApdA and related oligonucleotides by vacuum-UV radiation
      (above 7 eV), which generally indicate a simple, selective dissociation at the 3'
      side of the deoxypentose as observed with the soft X-rays, an hypothesis is
      presented on the molecular mechanism of radiation-induced breakage of
      phosphoester bonds that led to the selective 3' breakage, based on the
      differential flexibility of torsion angles of C3'-O3'-P and C4'-C5'-O5'-P groups
      in relation to those of the sugar ring.

PMID- 1355507
TI  - Radiation-induced apoptosis: its role in a MADCaT (mitosis-apoptosis
      differentiation-calcium toxicity) scheme of cytotoxicity mechanisms.

PMID- 1355506
TI  - Splitting of cis-syn cyclobutane thymine-thymine dimers by radiolysis and its
      relevance to enzymatic photoreactivation.
AB  - The 137Cs-gamma-irradiation of cis-syn thymine-thymine cyclobutane type dimers
      has been studied in aqueous solution. The mechanism of thymine dimer cleavage by
      eaq-, CO2.-, OH.,SO4.-,Br2.- and isopropanol radicals was studied using high
      pressure liquid chromatography (HPLC). Evidence that the one-electron reductants
      studied induce dimer cleavage partially by a chain reaction is presented.
      Approximate values for the one-electron reduction potential of thymine-thymine
      are obtained and thermodynamic calculations are presented in order to predict the
      direction of electron transfer in the case of enzymatic photoreactivation.

PMID- 1355508
TI  - Genetic analysis of susceptibility to radiation-induced apoptosis of thymocytes
      in mice.
AB  - Genetic control of thymocyte susceptibility to radiation-induced apoptosis was
      investigated in BALB/cHeA, STS/A and five other strains of mice by counting
      pyknotic cells in a selected area of thymic cortex on histological specimens
      after whole-body X-irradiation. Number of dead cells increased almost linearly
      with doses (range 0.25-0.75 Gy) in BALB/cHeA and STS/A mice. However, dead cell
      counts in BALB/cHeA mice were more than twice those in STS/A mice at each dose.
      Of five other strains of mice, C57BL/6N and B10.BR mice exhibited a sensitive
      phenotype similar to BALB/cHeA mice, while C3H/HeAMsNrs and NFS/N mice showed a
      resistant phenotype similar to STS/A mice. A/J mice seemed to be rather
      resistant. A sex difference was not recognized in BALB/cHeA and STS/A mice.
      Resistance was dominant over susceptibility in the progenies of reciprocal
      crosses between the two strains, indicating an autosomal inheritance and no
      maternal effect. Segregation ratio of susceptible phenotype to resistant one in
      the backcrosses of female (BALB/cHeA x STS/A)F1 mice with male BALB/cHeA mice was
      not significantly different from 1:1 and all backcrosses of female (BALB/cHeA x
      STS/A)F1 mice with male STS/A mice exhibited a resistant phenotype. Results
      suggested that thymocyte susceptibility to radiation-induced apotosis is
      controlled by one major autosomal allele.

PMID- 1355509
TI  - Effects of caffeine on protein phosphorylation and cell cycle progression in X
      irradiated two-cell mouse embryos.
AB  - The G2 phase/mitosis transition in cleavage-stage mouse embryos is correlated
      with an increased phosphorylation of a defined set of proteins at 46, 35, 30, and
      29 kDa. Cell cleavage and the associated changes in protein phosphorylation are
      delayed after X-irradiation. To understand the mechanism of the caffeine-induced
      uncoupling of mitosis and the cellular reactions to DNA-damaging agents, we have
      studied the effects of caffeine treatment on cell cycle progression and protein
      phosphorylation in two-cell mouse embryos after X-irradiation. Caffeine alone had
      no effect on timing of and changes in phosphorylation associated with the
      embryonic cell cycle. In combination with X-rays, however, caffeine was able to
      override the radiation induced G2 block and restored the normal timing of these
      phosphorylation changes after X-irradiation. However, new additional changes in
      protein phosphorylation appeared after the combined treatment.
      Isobutylmethylxanthine (IBMX), a substance chemically related to caffeine but a
      more specific inhibitor of the phosphodiesterase that breaks down cyclic AMP,
      reduced the radiation induced G2 block from 4 to 5 h to about 1 h and restored
      the cell cycle associated changes in protein phosphorylation. However, the same
      new changes which appeared after the combined treatment of caffeine and X-rays
      were observed after the combination of IBMX and X-irradiation. IBMX specific
      changes in protein phosphorylation were detected in both the single and the
      combined treatment. These results indicate a similar action of caffeine and IBMX
      in overriding the radiation induced G2 block in two-cell mouse embryos.

PMID- 1355510
TI  - Adaptive response in mouse embryos?
AB  - Pre-implantation embryos of the mouse were studied for the occurrence of an
      adaptive response, i.e. induction of radio-resistance by a previous low dose.
      Various experimental designs were checked (initial doses between 3 and 10 cGy;
      second dose 2-6 Gy at 6-24 h after the first dose). Some of the experiments were
      carried out in exactly the same way that resulted in an adaptive response of
      human lymphocytes reported previously. However, when cell proliferation and
      differentiation of mouse embryos were examined, none of the conditions tested
      indicated the induction of an adaptive response.

PMID- 1355512
TI  - Induction of a cytogenetic adaptive response by exposure of rabbits to very low
      dose-rate gamma-radiation.

PMID- 1355511
TI  - Absence of adaptive response to low doses of X-rays in preimplantation embryos
      and spleen lymphocytes of an inbred mouse strain as compared to human peripheral
      lymphocytes: a cytogenetic study.
AB  - The adaptive response was studied in preimplantation embryos and spleen
      lymphocytes of a mouse inbred strain and in peripheral lymphocytes of three human
      donors, using chromosomal aberrations as the endpoint. Embryos were adapted to
      0.05 Gy X-ray 50 h post-conception either in vitro or in vivo and challenged 6 h
      later. Chromosome aberrations of the 8----16 cell stage mitoses were scored. No
      adaptive response was seen in the embryos. Of 14 female mice studied, an adaptive
      response was seen in spleen lymphocytes of only one mouse. However, because
      variable chromosomal aberration levels were observed in lymphocytes of different
      donors, it is concluded that the adaptive response detected was merely a result
      of this heterogeneity. In human peripheral lymphocytes an adaptive response was
      seen in all three donors. It is speculated that the inbred mouse strain used is
      deficient in the adaptive response.

PMID- 1355513
TI  - Enhanced sensitivity to neoplastic transformation by 137Cs gamma-rays of cells in
      the G2-/M-phase age interval.
AB  - C3H mouse 10T1/2 cells, exposed to low doses of fission-spectrum neutrons, have
      an enhanced frequency of neoplastic transformation if protracted exposures are
      used (Hill et al. 1982, 1984a, 1985). To explain this anomaly, a biophysical
      model was proposed (Elkind 1991a,b) having the following essential features: (1)
      a narrow age interval exists in the growth cycle of 10T1/2 cells in which cells
      have high sensitivities to transformation; (2) in the latter age interval, cells
      are also sensitive to killing; (3) with increasing dose, cells at ages earlier in
      the growth cycle are progressively delayed from entering the sensitive age
      window; and (4) with increasing dose, the transformation sensitivity of cells in
      the sensitive window is not expressed due to increased killing. Protracted low
      doses result in elevated frequencies because of less killing, and reductions in
      delays in cell progression. Therefore, transformation-sensitive cells can
      progress into the sensitive interval to replace those that have progressed out of
      it. The unique shape and radiobiological properties of cells in and around
      mitosis, led to the proposal that the sensitive window is mitosis and possible
      cells just preceding or just following M phase (Elkind 1991a,b). Because of the
      likelihood that the properties of the cells in a sensitive window would not be
      evident only when fission-spectrum neutrons are used, this study was undertaken
      using 137Cs gamma-rays. We have found that late G2- to M-phase 10T1/2 cells have
      a maximal sensitivity to neoplastic transformation as well as to killing by 137Cs
      gamma-rays.

PMID- 1355514
TI  - Transformation and radiosensitivity of human diploid skin fibroblasts transfected
      with activated ras oncogene and SV40 T-antigen.
AB  - Three normal human diploid cell strains were transfected with an activated Ha-ras
      oncogene (EJ ras) or SV40 T-antigen. Multiple clones were examined for
      morphological alterations, growth requirements, ability to grow under anchorage
      independent conditions, immortality and tumorigenicity in nude mice. Clones
      expressing SV40 T-antigen alone or in combination with ras protein p21 were
      significantly radioresistant as compared with their parent cells or clones
      transfected with the neo gene only. This radioresistant phenotype persisted in
      post-crisis, immortalized cell lines. Cells transfected with EJ ras alone showed
      no morphological alterations nor significant changes in radiosensitivity. Cell
      clones expressing ras and/or SV40 T-antigen showed a reduced requirement for
      serum supplements, an increase in aneuploidy and chromosomal aberrations, and
      enhanced growth in soft agar as an early cellular response to SV40 T-antigen
      expression. The sequential order of transfection with SV40 T-antigen and ras
      influenced radio-sensitivity but not the induction of morphological changes.
      These data suggest that expression of the SV40 T-antigen but not activated Ha-ras
      plays an important role in the radiosensitivity of human diploid cells. The
      radioresistant phenotype in SV40 T transfected cells was not related to the
      enhanced level of genetic instability seen in pre-crisis and newly immortalized
      cells, nor to the process of immortalization itself.

PMID- 1355515
TI  - Prenatal irradiation and spatial memory in mice: investigation of critical
      period.
AB  - Pregnant CD1 mice were exposed on various gestational or postnatal days to 1 Gy
      of 250 kV X-rays. Ten adult, male offspring from each exposure condition were
      tested in a radial arm maze. Compared to sham-exposed control mice, acquisition
      of spatial information was unimpaired in animals exposed on gestational days 13
      or 15, or on postnatal day 10, but animals exposed on gestational day 18 or
      postnatal day 1 showed sustained deficits in acquisition. These results appear
      consistent with the known time-course for the proliferation and migration of the
      dentate granule cells of the hippocampus in the mouse, and are discussed in
      relation to the dependence on hippocampal integrity of the acquisition and use of
      spatial information. The results suggest that comparable deficits in mental
      function might be expected in humans similarly exposed to ionizing radiation
      during periods of proliferation and migration of the dentate granule cells.

PMID- 1355516
TI  - Pharmacokinetics of fluorinated 2-nitroimidazole hypoxic cell radiosensitizers in
      murine peripheral nervous tissue.
AB  - We have previously reported that KU-2285, a 2-nitroimidazole with a fluorinated
      N1-substituent (-CH2-CF2CONH(CH2)nOH, n = 2), was a promising hypoxic cell
      radiosensitizer. In this study the pharmacokinetics of KU-2285 and its related
      compounds (n = 3 and n = 4) were compared with those of etanidazole (a 2
      nitroimidazole with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related
      compounds (n = 3 and n = 4) to assess the effects of incorporation of a CF2
      group. The lipophilicity of the fluorinated compounds was higher than that of
      etanidazole, as measured by the octanol/water partition coefficient. As the
      number of CH2 groups increased, the lipophilicity of the compounds in both the KU
      2285 and etanidazole series increased. The brain tissue levels of the fluorinated
      compounds were as low as those of the etanidazole derivatives, while the
      biological half-lives of the fluorinated compounds in peripheral nervous tissues
      were shorter than those of related non-fluorinated compounds.

PMID- 1355517
TI  - Neurological complications after 434 MHz microwave hyperthermia of the rat lumbar
      region including the spinal cord.
AB  - Hyperthermia was applied in the region of the vertebral column from the second to
      the fifth lumbar vertebra using a ring-shaped 434 MHz microwave radiator. In all
      experiments temperatures were measured at a 'reference' thermocouple which was
      placed against the fourth lumbar vertebra. After 60 min of heat treatment at
      'reference' temperatures of 43.0 degrees C, 44.0 degrees C and 45.0 degrees C (+/
      0.05 degrees C) the average maximal temperature inside the vertebral canal were
      42.6 degrees C, 43.0 degrees C and 43.8 degrees C (+/- 0.3 degrees C),
      respectively. At all 'reference' temperatures the maximal core temperature of the
      animal did not exceed 40.5 +/- 0.3 degrees C after 60 min of heat treatment.
      Dorsal skin and muscle temperatures in the treatment area reached 'reference'
      temperature, and transient skin and muscle necrosis was observed after treatment
      for 1 h at 'reference' temperatures at 44 degrees C and 45 degrees C.
      Temperatures in the peritoneal cavity approximately 1 mm ventrally of the
      vertebral column rose to 41.8 degrees C after 60 min at reference 43.0 degrees C.
      Treatment at spinal cord temperature 42.6 degrees C for 60 min did not induce any
      significant neurological effects. Motoric dysfunction of the hind legs, such as
      difficulties with walking, was observed after 60 min treatment at spinal cord
      temperatures of 43.0 degrees C or 43.8 degrees C. In addition, 24 h after
      treatment at 43.8 degrees C for 60 min loss of tail tonus was observed, as well
      as loss of sensory function in the hind limbs. Recovery from the neurological
      disorders, except for the loss of tail tonus, occurred within 2 weeks after
      treatment. Histopathological examination revealed necrosis in the central areas
      of the spinal cord at 3 days and complete necrosis at 7 days after treatment at
      43.8 degrees C for 60 min.

PMID- 1355518
TI  - The effect of chronic radiation on the humoral immune response of rainbow trout
      (Onchorhynchus mykiss Walbaum).
AB  - Two separate experiments have examined the effect of exposing rainbow trout to
      chronic gamma-radiation, commencing immediately after fertilization. In
      experiment 1 the period of exposure extended for 20 days with groups receiving
      mean dose rates of 1.87, 3.73 and 9.03 mGy h-1, and mean total accumulated doses
      of 0.83, 1.66 and 4.01 Gy respectively. At 5 months of age fish were tested for
      specific antibody response to dinitrophenol coupled to keyhole limpet haemocyanin
      (DNP-KLH) and there was no significant difference in titre between irradiated
      groups and unirradiated controls. In experiment 2 the exposure period was
      extended to 246 days from fertilization. Mean dose-rates to the three groups used
      were the same as in the first experiment until hatching at 21 days and then lower
      with rates of 0.99, 1.9, and 4.66 mGy h-1 to the free-swimming fish. The mean
      total accumulated doses over the whole irradiation period were 5.43, 10.53 and
      25.43 Gy respectively. The antibody response to DNP-KLH was significantly lower
      in trout receiving the highest dose-rate when compared with those of unirradiated
      controls or the lowest dose-rate group. The significance of these results is
      discussed in relation to radiation levels in areas of radioactive waste disposal,
      and results from a similar study published previously.

PMID- 1355519
TI  - Tumour and normal tissue responses to fractionated non-uniform dose delivery.
AB  - The dose-volume response of tumours and normal tissues is discussed in terms of
      'parallelity' and 'seriality'. The volume dependence of the radiation response of
      a tumour depends primarily on the eradication of all its clonogenic cells and the
      tumour has a parallel organization. The response of heterogeneous tumours is
      examined, and it is shown that a small resistant clonogen population may cause a
      low dose-response gradient, gamma. Injury to normal tissue is a much more complex
      and gradual process. It depends on earlier effects induced long before depletion
      of stem cells or differentiated cells that in addition may have a complex
      structural and functional organization. The volume dependence of the dose
      response relation of normal tissues is therefore described here by a new
      parameter, the 'relative seriality', s, of the infrastructure of the organ. The
      model is compared with clinical and experimental data on normal tissue response,
      and shows good agreement both with regard to the shape of dose-response relation
      and the volume dependence of the isoeffect dose. For example, the spinal cord has
      a high and the lung a low 'relative seriality', which is reasonable with regard
      to the organization of these tissues. The response of tumours and normal tissues
      to non-uniform dose delivery is quantified for fractionated therapy using the
      linear quadratic cell survival parameters alpha and beta. The steepness, gamma,
      and the 50% response dose, D50, of the dose-response relationship are derived
      both for a constant dose per fraction and a constant number of dose fractions.

PMID- 1355520
TI  - Intraventricular administration of thyrotrophin-releasing hormone (TRH)
      suppresses prolactin secretion and synthesis: a possible involvement of dopamine
      release by TRH from rat hypothalamus.
AB  - The administration of thyrotrophin-releasing hormone (TRH) causes a variety of
      dopamine-related biological events. To understand the specific role of TRH on rat
      hypothalamic dopamine neurones, we examined the in-vivo effects of
      intraventricular (i.c.v.) infusion of TRH on the release and synthesis of
      prolactin in the rat pituitary gland and on the changes in binding of [3H]MeTRH
      and dopamine turnover rates in rat hypothalamus. We have also examined the in
      vitro effects of TRH on the release of [3H]dopamine from dispersed
      tuberoinfundibular dopamine neurones. Female rats were treated with i.c.v.
      infusions of 1 mumol TRH/1 daily for 1, 3 and 7 days using Alzet osmotic pumps.
      Following 7 days of treatment the serum prolactin concentrations were
      significantly decreased. A reduction in hypothalamic TRH-binding sites (Bmax) was
      also apparent but the dissociation constant (Kd) was unaffected. Northern blot
      analysis of total RNA isolated from the pituitary glands of control animals using
      32P-labelled prolactin cDNA as a probe indicated the presence of three species of
      prolactin gene transcripts of approximately 3.7, 2.0 and 1.0 kb in size, and
      these were decreased by TRH treatment. We examined the turnover rate of dopamine
      in the rat hypothalamus when TRH was administered i.c.v. for 7 days. There was a
      significant increase in 3,4-dihydroxyphenylacetic acid/dopamine ratio with TRH
      treatment. Moreover, exposure to TRH stimulated [3H]dopamine release from rat
      tuberoinfundibular neurones in a time- and dose-dependent manner. Dopamine
      receptor antagonists such as SCH23390 and (-)sulpiride, and other neuropeptides
      such as vasoactive intestinal peptide and oxytocin did not affect TRH-stimulated
      [3H]dopamine release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355521
TI  - Structural changes by sulfoxidation of phenothiazine drugs.
AB  - The side-chain conformations of psychoactive phenothiazine drugs in crystals are
      different from those of biologically inactive ring sulfoxide metabolites. This
      study examines the potential energies, molecular conformations and electrostatic
      potentials in chlorpromazine, levomepromazine (methotrimeprazine), their
      sulfoxide metabolites and methoxypromazine. The purpose of the study was to
      examine the significance of the different crystal conformations of active and
      inactive phenothiazine derivatives, and to determine why phenothiazine drugs lose
      most of their biological activity by sulfoxidation. Quantum mechanics and
      molecular mechanics calculations demonstrated that conformations with the side
      chain folded over the ring structure had lowest potential energy in vacuo, both
      in the drugs and in the sulfoxide metabolites. In the sulfoxides, side chain
      conformations corresponding to the crystal structure of chlorpromazine sulfoxide
      were characterized by stronger negative electrostatic potentials around the ring
      system than in the parent drugs. This may weaken the electrostatic interaction of
      sulfoxide metabolites with negatively charged domains in dopamine receptors, and
      cause the sulfoxides to be virtually inactive in dopamine receptor binding and
      related pharmacological tests.

PMID- 1355522
TI  - Elevated soluble c-erbB-2 antigen levels in the serum and effusions of a
      proportion of breast cancer patients.
AB  - PURPOSE: An enzyme-linked immunosorbent assay (ELISA) for the extracellular
      domain of the c-erbB-2 oncogene product was developed and evaluated to determine
      if soluble c-erbB-2 could be detected in the serum and effusions of cancer
      patients. PATIENTS AND METHODS: Sera from 208 previously untreated or progressing
      cancer patients and 69 healthy controls were assayed in a double-antibody
      sandwich ELISA that used two monoclonal antibodies to the native extracellular
      domain of the c-erbB-2 receptor. Fisher's exact test was used to analyze the
      statistical significance of the frequency of elevated serum c-erbB-2 levels.
      Immunoprecipitation and Western blotting were used to characterize further the c
      erbB-2 immunoreactivity in the serum of four breast cancer patients. RESULTS:
      Sera from 12 of 53 patients (23%) with metastatic or locally advanced breast
      cancer, zero of 69 controls, one of 31 patients with ovarian cancer (3%), and two
      of 124 other cancer patients (2%) had soluble c-erbB-2 values greater than or
      equal to 5 U/mL. The number of breast cancer patients with elevated serum c-erbB
      2 levels was significantly greater than that of the control group (P less than
      .0001), the ovarian cancer group (P less than .03), and the other cancers group
      (P less than .0001). Also, two of five effusions (40%) from breast cancer
      patients had an elevated soluble c-erbB-2 antigen level, compared with zero of 17
      effusions from patients with benign diseases. Western blotting of four sera from
      breast cancer patients with elevated serum c-erbB-2 antigen levels produced bands
      of approximately 105 kD that seemed to correlate in intensity with increasing
      ELISA serum levels. CONCLUSION: Serum c-erbB-2 levels are elevated in
      approximately one fourth of patients with locally advanced or metastatic breast
      cancer.

PMID- 1355523
TI  - Phase I trial of intraperitoneal taxol: a Gynecoloic Oncology Group study.
AB  - PURPOSE: To evaluate the safety and pharmacology of the intraperitoneal (IP)
      administration of the antineoplastic agent taxol. PATIENTS AND METHODS: Twenty
      five pretreated patients who were entered onto a phase I clinical trial; 24 had
      advanced ovarian cancer. Patients were treated with taxol administered IP in 2 L
      of normal saline every 3 to 4 weeks. The starting dose was 25 mg/m2. There were
      no intrapatient dose escalations. RESULTS: The dose-limiting toxicity was the
      development of severe abdominal pain at taxol doses more than 175 mg/m2. Moderate
      leukopenia (WBC count less than 2,000/mm3) was observed at IP doses of greater
      than or equal to 175 mg/m2. The exposure of the peritoneal cavity (peak levels
      and area under the time-versus-concentration curve [AUC]) to taxol after IP
      delivery exceeded that of the plasma by approximately 1,000-fold. However,
      concentrations of the agent previously shown to produce cytotoxicity in
      experimental systems were demonstrated in the systemic compartment after regional
      delivery, which was considered important. Significant concentrations of taxol
      persisted within the peritoneal cavity for more than 24 to 48 hours after a
      single IP installation. Several antitumor responses, which included control of
      platinum-refractory ascites, were documented. CONCLUSION: Taxol can be delivered
      by the IP route with both an acceptable toxicity profile and a major
      pharmacokinetic advantage for cavity exposure.

PMID- 1355524
TI  - Electrophysiological and pharmacological characterization of perforant path
      synapses in CA1: mediation by glutamate receptors.
AB  - 1. With the use of hippocampal slices from adult rats, we studied monosynaptic
      potentials in CA1 evoked by stimulating either the perforant pathway or the
      Schaffer collaterals. Excision of region CA3 and the dentate gyrus prevented
      polysynaptic excitation of CA1 and facilitated interpretation of the
      extracellular potentials. 2. Laminar profiles distinguished the population
      excitatory postsynaptic potentials (pEPSPs) in CA1 evoked by stimulating the
      Schaffer collaterals and the perforant path. Stimulating the perforant path
      evoked short-latency negative-going pEPSPs in s. lacunosum-moleculare of CA1 and
      positive-going pEPSPs in s. radiatum. Stimulating the Schaffer collaterals evoked
      negative-going pEPSPs in s. radiatum. 3. A pharmacological manipulation also
      distinguished the two pathways in CA1. The selective GABAB agonist baclofen
      greatly decreased the slope of pEPSPs evoked by stimulating the Schaffer
      collaterals but did not decrease the slope of pEPSPs evoked by stimulating the
      perforant path. 4. Combined bath application of the glutamate receptor
      antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 2-amino-5
      phosphonopentanoic acid (APV) abolished the negative-going pEPSPs in s. lacunosum
      moleculare evoked by stimulating the perforant pathway. This application of DNQX
      and APV revealed a positive-going field potential that was blocked by bath
      application of the gamma-aminobutyric acid (GABA) receptor antagonists picrotoxin
      or bicuculline. 5. Although the glutamate-mediated component of the response
      evoked by stimulating the perforant path was apparently excitatory, we never
      observed a population spike in s. pyramidal evoked by stimulating the perforant
      path.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355525
TI  - Dual-component miniature excitatory synaptic currents in rat hippocampal CA3
      pyramidal neurons.
AB  - 1. Spontaneous miniature synaptic events were studied with tight-seal whole-cell
      recordings from CA3 neurons maintained in the hippocampal slice from immature
      rats (3-15 days). CA3 neurons suffer a constant, high-frequency barrage of
      inhibitory synaptic input. When inhibitory postsynaptic currents were suppressed
      by bicuculline, a smaller contribution from excitatory synapses was revealed. 2.
      Addition of tetrodotoxin (TTX) removed a persistent inward current and
      substantially reduced the baseline noise facilitating the detection of
      "miniature" excitatory currents. Addition of hyperosmotic media increased the
      frequency of spontaneous excitatory postsynaptic currents (EPSCs). 3. Under both
      physiological and elevated potassium conditions, individual spontaneous miniature
      EPSCs (10-30 pA amplitude) were composed of components mediated by N-methyl-D
      aspartate (NMDA) and non-NMDA receptors as determined by their voltage
      dependence, time course, and sensitivity to selective antagonists. 6-Cyano-7
      nitro-quinoxaline-2,3-dione (CNQX) or D-2-amino-5-phosphonovaleric acid (D-APV)
      shifted the amplitude distribution of miniature EPSCs to a smaller mode at both
      +40 mV and -40 mV. Similar to EPSCs recorded in CA1 neurons, the rise and decay
      times of the NMDA receptor component were slower than those of the non-NMDA
      component. The time course of the non-NMDA component was voltage independent. 4.
      In 13 of 21 neurons, no correlation existed between individual EPSC rise times
      and their corresponding halfwidth, peak amplitude, or decay time constant. This
      suggests that the large range of EPSC kinetics observed in each individual neuron
      was not due solely to cable attenuation of EPSCs widely distributed over the
      dendritic tree. Plots of the mean EPSC rise time against mean halfwidth for each
      cell, however, revealed a striking correlation, suggesting that in neonates,
      active synapses may be grouped in a restricted region of the dendritic tree and
      as such are subject to similar amounts of dendritic filtering. 5. The
      electrotonic length of CA3 neurons (L = 0.52) predicted that at this maturity the
      electrotonic compactness of the neuron facilitated voltage control over all but
      the most distal synapses. The reversal potential of the fast component of
      spontaneous events was close to 0 mV, whereas the reversal potential of
      exogenously applied kainate and NMDA was more positive. This discrepancy likely
      reflects a compromise of the voltage clamp by the activation of conductances
      distributed over the entire cell.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1355526
TI  - Effect of stimulus contrast and size on NMDA receptor activity in cat lateral
      geniculate nucleus.
AB  - 1. We studied the effect of varying excitatory and inhibitory drive on the N
      methyl-D-aspartate (NMDA) receptor-mediated component of the visual responses of
      neurons in the cat dorsal lateral geniculate nucleus (dLGN) by varying the
      contrast and size of stimuli presented to the receptive fields of these cells. 2.
      Cells were classified as either on- or off-center, X or Y, and lagged or
      nonlagged. Stimulus contrast, and hence the amount of excitatory drive, was
      varied by changing the brightness of a spot, whose size and location matched the
      cell's receptive field center, relative to a fixed background luminance.
      Responses to varying contrast were collected from each cell before, during, and
      after iontophoretic application of D-2-amino-5-phosphonovaleric acid (D-APV), a
      specific NMDA receptor antagonist. From each contrast-response plot, a sigmoidal
      curve fit yielded five parameters on which we examined the effect of D-APV: the
      threshold contrast, saturation contrast, contrast at half saturation (C50), slope
      (gain) at C50, and saturation response. 3. In most cells, application of D-APV
      reduced both the saturation response and the gain of the contrast-response curve,
      but did not reduce or change significantly the threshold contrast, saturation
      contrast, or C50. 4. Cells varied in their sensitivity to D-APV, but for any
      given cell, the D-APV-sensitive component was nearly always a linear function of
      the control visual response level. Thus, for a spot of optimal size, there was a
      constant proportion of the visual response attributable to NMDA receptors,
      regardless of the amplitude of the response. 5. When the effect of D-APV on the
      visual responses to an optimal spot at varying contrasts was compared among
      different classes of dLGN cells, the visual responses of lagged X cells were
      reduced to a greater extent than those of either nonlagged X cells or the
      combined population of nonlagged X and Y cells. 6. Stimulus size (spot diameter)
      was also varied systematically at a fixed contrast to vary the inhibitory drive
      to dLGN cells. As stimulus size was increased, the response first increased
      because of increased stimulation of the receptive field center and then decreased
      because of increasing amounts of surround inhibition. 7. The D-APV-sensitive
      component of individual cell responses was greater when the stimulus spot was
      less than or equal to optimal size than when the spot was larger. Thus the
      contribution of NMDA receptors to the visual response decreased with increasing
      surround inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1355527
TI  - Excessive intracellular Ca2+ inhibits glutamate-induced Na(+)-K+ pump activation
      in rat hippocampal neurons.
AB  - 1. The effects of increased intracellular Ca2+ concentration ([Ca2+]i) on Na(+)
      K+ pump activity in CA1 pyramidal neurons of rat hippocampal slices were
      investigated. The postglutamate hyperpolarization (PGH), which follows glutamate
      (GLU)-induced depolarization (GD), was used as an index of Na(+)-K+ pump
      activity, as was a ratio of PGH area to the preceding GD area (PGH ratio). 2.
      Perfusion of slices with saline containing Ca2+ ionophore (A23187, 10 microM)
      inhibited the PGH without producing apparent signs of cell deterioration. A 60
      100% (85 +/- 15%, mean +/- SD) reduction in the PGH ratio occurred after 20-50
      min of A23187 superfusion in 12 of 18 neurons tested. Complete abolition of the
      PGH occurred in 8 of these 12 cells exposed to A23187 for 30-120 min. 3.
      Application of A23187 in Ca(2+)-free/high-Mg2+ solution did not abolish the PGH,
      although small (less than 50%; 37 +/- 10%) reductions in the PGH ratio were
      observed after perfusion of 50 min or longer in five neurons tested. 4.
      Intracellular injection of the Ca2+ chelator bis-(o-amino-phenoxy)-N,N,N',N'
      tetraacetic acid (BAPTA, 300-400 mM) blocked inhibition of the PGH by A23187.
      After 50 min of perfusion with Ca2+ ionophore, no reduction of the PGH ratio was
      observed in five neurons tested. 5. Rundown of the PGH without apparent change in
      membrane properties was observed in three neurons that were stable for greater
      than 2-3 h, allowing repetitive GLU applications. 6. Block of the PGH produced by
      a Na(+)-K(+)-adenosinetriphosphatase (ATPase) inhibitor (strophanthidin)
      prolonged the duration of GDs because of a delay in repolarization.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1355528
TI  - Extracellular alkaline shifts in rat hippocampal slice are mediated by NMDA and
      non-NMDA receptors.
AB  - 1. The pharmacology of synaptically evoked extracellular alkaline shifts was
      studied in the CA1 area of rat hippocampal slices. 2. Stimulus-evoked
      alkalinizations were unaffected by 2-amino-5-phosphonovalerate (APV) (20 microM).
      3. 6-Cyano-7-nitro-nitroquinoxaline-2,3-dione (CNQX) (10 microM) inhibited the
      alkalinizations. In the continued presence of CNQX, an APV-sensitive, picrotoxin
      insensitive, alkaline shift was elicited in low Mg2+ media. 4. Antidromic
      stimulation produced small alkaline shifts in comparison with orthodromic
      activation. 5. Our results demonstrate that in the hippocampal CA1 region,
      synaptically evoked alkalinizations can arise through both N-methyl-D-aspartate
      (NMDA) and non-NMDA glutamate receptors. These responses cannot be explained by
      cell firing per se.

PMID- 1355529
TI  - Society of Oral Physiology Store Kro Group. 17th biennial meeting. Bonn, Germany,
      23-26 May 1991. Abstracts.

PMID- 1355530
TI  - Lysosomes as key organelles in the pathogenesis of prion encephalopathies.
AB  - The causation, structural origin, and mechanism of formation of spongiform
      lesions in transmissible encephalopathies are unknown. We have used immunogold
      electron microscopy to locate ubiquitin conjugates, hsp 70, and beta
      glucuronidase (markers of the lysosomal compartment) and prion protein (PrP) in
      both control and scrapie-infected mouse brain. In scrapie-infected brain,
      lysosomes and lysosome-related structures (multivesicular and tubulovesicular
      dense bodies) are present in abnormally high numbers in neuronal cell processes.
      These structures contain PrP, together with the lysosomal markers ubiquitin
      conjugates, hsp 70, and beta-glucuronidase, which could also be identified
      spilling from tubulovesicular dense bodies into areas of early rarefaction in
      neuronal processes; we suggest that these areas of rarefaction are the precursor
      lesions of spongiform change. We advance the hypothesis that spongiform change is
      brought about by cytoskeletal disruption in neuronal processes caused by
      liberation of hydrolytic enzymes from lysosomes overloaded with the abnormal
      isoform of PrP (PrPsc). We suggest that the lysosomal system is probably acting
      as the bioreactor for processing of normal PrP to the abnormal isoform. The
      continuous production of increasing quantities of abnormal PrPsc in lysosome
      related bodies will eventually cause disruption of the lysosomal membrane with
      destruction of the neuronal cytoskeleton and the initiation of vacuolation.
      Later, death of the cell will be associated with release of the PrPsc isoform
      into the extracellular environment. Repeated rounds of phagocytosis, lysosomal
      biogenesis of PrPsc, lysosomal membrane rupture, hydrolytic enzyme release, and
      neuronal lysis will lead to an exponential increase in cell damage and cell
      death.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355531
TI  - Tumour suppressor gene products, proliferation, and differentiation markers in
      lung neuroendocrine neoplasms.
AB  - Typical carcinoid, atypical carcinoid, and small cell lung cancer (SCLC) fall
      within the spectrum of neuroendocrine lung neoplasms. This paper investigates the
      immunohistochemical expression of the products of tumour suppressor genes p53 and
      retinoblastoma (RB), together with proliferation (PCNA and Ki67) and
      neuroendocrine differentiation markers, in 14 typical carcinoids, ten atypical
      carcinoids, four borderline atypical carcinoid/SCLC, and 11 SCLC. We demonstrated
      that the phosphoprotein p53 and RB product can be immunolocalized on routine
      histological material. p53 protein was absent in all typical and atypical
      carcinoids, while it was abnormally expressed in eight SCLC and one borderline
      case. RB product was detected in all typical carcinoids and in two atypical
      carcinoids, while it was consistently absent in the other cases. PCNA-labelled
      cells were less than 4 per cent in typical carcinoids, about 40 per cent in
      atypical carcinoids, and over 70 per cent in SCLC. PCNA labelling index
      discriminates between typical and atypical carcinoids. Neuroendocrine
      differentiation was evaluated by a semi-quantitative method: a mean score value
      was obtained, which was high in typical carcinoids, intermediate in atypical
      carcinoids, and low in SCLC. Our data was obtained, which was high in typical
      carcinoids, intermediate in atypical carcinoids, and low in SCLC. Our data show
      that the decrease in neuroendocrine features from typical carcinoid to SCLC is
      paralleled by an increase in proliferative activity and by an altered expression
      of tumour suppressor gene products. The above findings have diagnostic relevance.

PMID- 1355532
TI  - Another cautionary note on the use of PCNA.

PMID- 1355533
TI  - Mosaic expression of brush-border enzymes in infants with chronic diarrhea and
      malnutrition.
AB  - The chronic diarrhea observed in young malnourished infants that is sensitive to
      dietary glucose and other carbohydrates is associated with variable degrees of
      patchy mucosal villous atrophy. To explore intrinsic mucosal function in the
      pathogenesis of this alimentary intolerance, we have conducted an
      immunohistologic investigation of brush-border enzyme proteins of clinically
      obtained, mucosal biopsy samples. We used a group of monoclonal antibodies
      against human brush-border aminopeptidase, sucrase/isomaltase (SI), maltase, and
      lactase enzyme proteins. SI was strongly and uniformly expressed in crypts and
      villi of 11 of the 14 subjects; in 3 subjects, however, SI was expressed in a
      mosaic pattern. Maltase and lactase were occasionally absent, but more commonly
      were expressed in a mosaic distribution. The mosaic expression of brush-border
      enzyme proteins has been reported in congenital enzyme deficiencies associated
      with normal intestinal histology. We report the mosaic expression of brush-border
      enzyme proteins as a functional alteration associated with a pathological lesion
      of the mucosa in infants with chronic diarrhea. Our observation challenges the
      existing concept of ontogenic regulation of brush-border enzyme activity.

PMID- 1355534
TI  - Familial microvillous atrophy: a clinicopathological survey of 23 cases.
AB  - Twenty-three cases of microvillous atrophy were reviewed to determine clinical
      and morphological characteristics of the disease. Congenital and late-onset forms
      of presentation were clearly identified in which the late-onset cases appeared to
      have a better prognosis. Three different, and distinctive, appearances of the
      proximal small intestinal mucosa were found. Careful orientation of mucosal
      samples allowed a temporal sequence of events to be delineated in which the first
      morphological abnormality to be detected in the epithelium was the accumulation
      of "secretory granules"; microvillous inclusions were seen in older cells in the
      upper villous region. It is suggested that, in familial microvillous atrophy,
      diarrhoea and disorganisation of the brush border assembly occur as a consequence
      of a more fundamental defect that affects the intracellular traffic of certain
      cell components, as indicated by the accumulation of "secretory granules."

PMID- 1355535
TI  - Levels and molecular forms of gastrin and somatostatin in plasma and in gastric
      contents of infants after section delivery.
AB  - We measured the pH of the gastric contents, as well as the gastrin- and
      somatostatin-like immunoreactivity in both plasma and gastric content samples,
      obtained from 23 infants delivered at term by elective cesarean section (ECS). In
      addition, we characterized the molecular forms of gastrin and somatostatin by
      high performance liquid chromatography. The median pH value of the gastric
      contents was found to be 6.78 (range 4.93-7.35). The median gastrin concentration
      in plasma was 54 pmol/L (range 29-190 pmol/L), which was significantly higher (p
      less than 0.0005) than the concentration recorded in the gastric contents, 6
      pmol/L (range 0-680 pmol/L). The median somatostatin concentration in plasma was
      12 pmol/L (range 4-40 pmol/L), which was significantly lower (p less than 0.0001)
      than the concentration found in the gastric contents, 128 pmol/L (range 15-488
      pmol/L). Gastrin- and somatostatin-like immunoreactivity in both plasma and
      gastric contents were found to correspond to nonsulfated gastrin-34 and
      somatostatin-14, respectively. These data suggest that acid secretion is absent
      or low in infants immediately following ECS, although gastrin and somatostatin
      are being released into the circulation as well as into the gastric lumen. The
      different ratio between the concentration in plasma and gastric contents of
      gastrin (10:1) compared with that of somatostatin (1:10) might be related to the
      fact that gastrin exerts endocrine actions preferentially, whereas somatostatin
      is presumed to exert local paracrine effects on the gastric mucosa.

PMID- 1355536
TI  - Comparison of 5.8S ribosomal DNA sequences among the basidiomycetous yeast genera
      Cystofilobasidium, Filobasidium and Filobasidiella.
AB  - Nucleotide sequences obtained from regions of the ribosomal DNA repeat were
      compared by phylogenetic methods and combined with a statistical evaluation to
      clarify the relationships among the genera Cystofilobasidium, Filobasidium (F.)
      and Filobasidiella (Fl.), to assess the affinity of Filobasidiella neoformans and
      Filobasidiella depauperata, and to compare the varieties of Fl. neoformans. With
      appropriate primers, the nuclear 18S, 5.8S and internal transcribed spacer (ITS)
      regions of the ribosomal RNA genes (rDNA) of 10 strains were amplified with the
      polymerase chain reaction. The resulting DNA products were compared by digestion
      with endonucleases and analysis of restriction fragments. Single strands of the
      5.8S rDNA and ITS regions were subsequently sequenced by the dideoxy method.
      Statistical support for the phylogeny inferred from parsimony analysis of aligned
      5.8S rDNA sequences was determined by bootstrapping. There were no nucleotide
      substitutions in this region, nor in the ITS, among strains of Fl. neoformans
      that differ in variety and serotype. There was strong support for retaining Fl.
      depauperata and Fl. neoformans in the same genus, but nucleotide substitutions
      can be used to distinguish the two species. There was no support for combining
      the genera Filobasidium, Filobasidiella or Cystofilobasidium.

PMID- 1355537
TI  - Cross-linked chitosan microspheres: preparation and evaluation as a matrix for
      the controlled release of pharmaceuticals.
AB  - Chitosan microspheres having good spherical geometry and a smooth surface were
      prepared by the glutaraldehyde cross-linking of an aqueous acetic acid dispersion
      of chitosan in paraffin oil using dioctyl sulphosuccinate as the stabilizing
      agent. Microspheres having different degrees of swelling were made by varying the
      cross-linking density. Microspheres were prepared by incorporating theophylline,
      aspirin or griseofulvin. Drug incorporation efficiencies exceeding 80% could be
      achieved for these drugs. In-vitro release studies of these drugs were carried
      out in simulated gastric and intestinal fluids at 37 degrees C. It was observed
      that the drug release rates were influenced by the cross-linking density,
      particle size and initial drug loading in the microspheres.

PMID- 1355538
TI  - Safety aspects of non-ionic surfactant vesicles: a toxicity study related to the
      physicochemical characteristics of non-ionic surfactants.
AB  - Two different toxicity models were used to assess the relationship between the
      physicochemical properties of non-ionic surfactant vesicles (NSVs), and the
      safety of these vesicles for topical drug administration. The vesicles used in
      this study consisted of polyoxyethylene alkyl ethers (CnEOm) in which the number
      of C atoms (n) varied between 12 and 18 and the number of oxyethylene units (m)
      between 3 and 7. The physicochemical properties of the vesicles are described in
      terms of hydrophilic-lipophilic balance (HLB) values, and critical micelle
      concentrations (CMC), and the rigidity of the bilayers as determined by the gel
      liquid transition temperatures and the cholesterol content of the bilayers. The
      first toxicity model, comprising the measurement of the ciliary beat frequency,
      is a tool to assess the safety of intranasally applied formulations. Studies
      using this ciliotoxicity model revealed that by increasing the length of the
      alkyl chain of the surfactant, a decrease in toxicity was observed. The opposite
      correlation was found if the length of the polyoxyethylene headgroup was
      increased. Furthermore, it was observed that gel-state vesicles produce less of
      an effect on the ciliary beat frequency than liquid state vesicles. The second
      toxicity model, comprising the determination of cell proliferation of human
      keratinocytes, is a method to assess skin irritancy. In contrast to the
      ciliotoxicity model the length of the polyoxyethylene headgroup and of the alkyl
      chains did not seem to have an effect on the safety of the vesicles.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1355539
TI  - Development of a prodrug of salicylic acid, salicylic acid-L-alanine conjugate,
      utilizing hydrolysis by rabbit intestinal microorganisms.
AB  - The hydrolysis of salicylic acid-L-alanine conjugate (salicyl-L-alanine)
      following oral, intravenous, intracaecal and rectal administration (60, 10, 5 and
      5 mg kg-1, respectively: salicylic acid equivalent) was examined in rabbits.
      Salicylic acid was detected in the blood 2 h after oral administration of salicyl
      L-alanine and reached a maximum concentration at 10 h, whereas salicyl-L-alanine
      was rapidly eliminated. In contrast, unchanged salicyl-L-alanine only was found
      following intravenous administration of salicyl-L-alanine, suggesting that
      presystemic de-conjugation of salicyl-L-alanine was involved. The intestinal
      mucosal de-conjugation of salicyl-L-alanine was not recognized in the in-situ
      intestinal sac preparation with complete mesenteric venous blood collection.
      Immediate and very extensive salicylic acid formation in the caecum was found
      following intracaecal administration of salicyl-L-alanine. After oral
      pretreatment of rabbits with kanamycin sulphate, a significant inhibition of
      salicylic acid formation following intracaecal administration of salicyl-L
      alanine was observed, indicating that the intestinal microorganisms were
      responsible for the biotransformation of salicyl-L-alanine. In-vitro incubation
      of salicyl-L-alanine with gut contents showed that the major source of its
      hydrolysis was the hind gut. Consequently, the blood concentration of salicylic
      acid was prolonged extensively following rectal administration of salicyl-L
      alanine, suggesting the usefulness of salicyl-L-alanine as a prodrug of salicylic
      acid.

PMID- 1355540
TI  - Roles of PMN leucocytes, platelets and some mediators in rat hind-paw oedema
      induced by two phospholipase A2 enzymes from Trimeresurus mucrosquamatus venom.
AB  - Two phospholipase A2 (PLA2) enzymes, TMVPLA2 I and TMVPLA2 II, isolated from
      Trimeresurus mucrosquamatus venom induced rat hind-paw oedema. Recovered
      myeloperoxidase activity increased within 1 h and was greatly elevated in the rat
      paw 3-6 h after subplantar injection of these venom PLA2 enzymes. Methotrexate
      pretreatment significantly reduced not only the peripheral leucocyte count but
      also venom PLA2-induced paw oedema. In rat isolated PMN leucocyte suspension,
      venom PLA2 induced superoxide radical formation. Paw swelling caused by TMVPLA2 I
      or TMVPLA2 II was only slightly or not, respectively, reduced in the rats
      pretreated with anti-platelet plasma, which reduced peripheral blood platelet
      count by greater than 96%, suggesting platelets are not involved. In isolated
      platelet preparation, TMVPLA2 I induced platelet activation in a concentration
      dependent manner, while TMVPLA2 II had no effect. Pretreatment with
      diphenhydramine/methysergide greatly suppressed the oedematous responses caused
      by the two venom PLA2 enzymes; the residual responses were significantly further
      depressed by aspirin. The oedematous responses caused by the enzymes were also
      suppressed by FPL 55712, BW 755C, dexamethasone, superoxide dismutase/catalase,
      isoprenaline and terbutaline. However, BN 52021 and L 652731, both platelet
      aggregating factor antagonists, were not effective on these responses. Thus, in
      addition to histamine and 5-hydroxytryptamine release by the mast cells in PLA2
      induced paw oedema (Wang & Teng 1990), the results of this study indicate minor,
      but significant, roles for neutrophils and inflammatory mediators including
      prostaglandins, leukotrienes and superoxide radicals.

PMID- 1355542
TI  - Decarboxylation of L-dopa in the rat isolated vascularly perfused small
      intestine: contribution to systemic elimination and dose-dependent first pass
      effect.
AB  - The contribution of the rat small intestine to systemic and presystemic
      elimination of L-dopa was studied. When L-dopa was administered into the vascular
      perfusate, a systemic extraction ratio of 0.38 was found, the major part being
      decarboxylated to dopamine. The intestinal L-dopa clearance was estimated to be
      17.1 mL min-1 kg-1. Thus, L-dopa intestinal clearance in rat represents up to at
      least 20% of the total body clearance. After luminal administration of L-dopa 83
      88% of the administered dose was absorbed within 60 min. The total amount of L
      dopa appearing in the vascular perfusate increased more than proportionally to
      the increase in the dose. In contrast, the amount of dopamine increased less than
      proportionally to the dose. As a result, the intestinal first pass appeared to be
      strongly dose-dependent. Since the total percentage absorbed from the lumen was
      independent of the administered dose and the total amount that appeared in the
      vascular perfusate increased linearly with the dose, the dose dependency was
      probably due to saturation of intestinal L-dopa decarboxylation.

PMID- 1355541
TI  - Comparison of kinin-forming and amidolytic activities of four trimucases, oedema
      producing and kinin-releasing enzymes, from Trimeresurus mucrosquamatus venom.
AB  - Four kinin-releasing enzymes, trimucase I, II, III and IV, isolated from
      Trimeresurus mucrosquamatus venom (TMV) caused rat hind-paw swelling. Trimucase I
      and III were less potent than trimucase II and IV in this effect. Pretreatment
      with diphenhydramine or methysergide significantly reduced trimucase-induced paw
      swelling, while aspirin had no effect. Cellulose sulphate pretreatment suppressed
      the oedematous responses elicited by trimucases. The residual response was
      further depressed by diphenhydramine and methysergide. Trimucases also caused
      kinin generation in-vitro from rat plasma. This kinin-forming activity was in the
      order of trimucase II greater than IV greater than or equal to III greater than I
      greater than TMV. All trimucases hydrolysed chromogenic peptides N-benzoyl-Pro
      Phe-Arg p-nitroanilide, N-benzoyl-Phe-Val-Arg p-nitroanilide and DL-Val-Leu-Arg p
      nitroanilide; the order of this amidolytic activity was trimucase I greater than
      II greater than III greater than or equal to IV. These data indicate that the
      effects of venom kinin-releasing enzymes on plasma kininogen are not parallel to
      their amidolytic effects.

PMID- 1355543
TI  - Pharmacological evaluation of the histamine H1 and 5-HT blocking properties of 2
      N-(carboxamidinonormianserin) (FCC5): in-vitro studies.
AB  - Some in-vitro pharmacological effects of a novel analogue of mianserin, 2
      carboxamidino-1,2,3,4,10,14b-hexahydrodibenzo (c,f) pyrazino (1,2-alpha) azepine
      hydrochloride (FCC5) have been studied. FCC5 was a non-competitive antagonist of
      both histamine-induced contractions of the guinea-pig ileum and 5-HT-induced
      contractions of rat fundal strips with pD'2 values of 6.13 and 5.57,
      respectively. The insurmountable antihistaminic effect of FCC5, 100 nM, in the
      guinea-pig isolated ileum was not removed by washing. FCC5, 10-100 nM, had no
      effect on responses to acetylcholine or barium chloride of the guinea-pig
      isolated ileum. In guinea-pig isolated right atria, FCC5, 1-30 microM, had no
      effect on H2-receptor-mediated chronotropic responses to histamine. FCC5, 10-1000
      nM, had no alpha 2-adrenoceptor antagonist activity, as assessed by lack of
      effect on the inhibitory responses to B-HT 920 in the electrically stimulated rat
      isolated vas deferens. FCC5 resembles mianserin by being a potent, non
      competitive antagonist at histamine H1 and 5-HT receptors, but differs from
      mianserin in a number of respects including having much less effect at alpha 2
      adrenoceptors.

PMID- 1355544
TI  - Effects of the calcium antagonists diltiazem, verapamil and nitrendipine on the
      contractile responses of guinea-pig isolated ileum to electrical stimulation or
      carbachol.
AB  - The effects of the organic Ca2+ antagonists nitrendipine, verapamil and diltiazem
      on the cholinergic contractile responses induced by field electrical stimulation
      or carbachol (0.1 microM) and on contractions evoked by high concentration KCl
      (30 mM) were studied in isolated preparations from the guinea-pig ileum. The
      three Ca2+ antagonists dose-dependently suppressed the contractile responses
      showing the same order of potency (nitrendipine greater than verapamil greater
      than diltiazem) with the three different types of stimulation. Comparison of the
      IC50 values of the Ca2+ antagonists for carbachol-, KCl- and electrically-evoked
      contractions demonstrated that the carbachol-evoked contractions were most
      sensitive to the inhibitory action of the antagonists tested. The presynaptic
      inhibitory effect of (Met)enkephalin (10 nM) on the electrically-evoked
      cholinergic contractions was only slightly potentiated by high concentrations (1
      or 10 microM) of nitrendipine and diltiazem and remained unchanged by verapamil.
      The results suggest that the Ca2+ antagonists tested block mainly the carbachol
      activated L-type Ca2+ channels on the smooth muscle cells, while the effects on
      the N-type Ca2+ channels are insignificant, except for the high concentrations of
      nitrendipine and diltiazem.

PMID- 1355545
TI  - Non-opioid-dependent inhibitory action of loperamide on cholinergic
      neurotransmission in canine isolated bronchial smooth muscle.
AB  - The effect of loperamide on cholinergic neurotransmission in canine bronchial
      smooth muscle was studied under isometric conditions in-vitro. Addition of
      loperamide decreased contractile responses to electrical field stimulation in a
      dose-dependent fashion, the maximal decrease from the control response and the
      IC50 value being 65.4 +/- 5.9% and 1.5 microM, respectively. In contrast,
      loperamide was without effect on the responses to exogenously administered
      acetylcholine. The inhibitory effect of loperamide was not altered by pre
      incubation of tissues with propanol, 6-hydroxydopamine, bicuculline, or naloxone.
      These results suggest that loperamide attenuates the neurally mediated airway
      contraction probably by inhibiting acetylcholine release from cholinergic nerve
      terminals through a non-opioid-dependent mechanism.

PMID- 1355546
TI  - The inhibitory effect of dopamine on cat gastric smooth muscle.
AB  - The inhibitory effect of dopamine has been studied in longitudinal and circular
      muscle strips of the cat gastric fundus. When tone was raised by transmural
      electrical stimulation and by administration of methacholine, dopamine
      concentration-dependently relaxed the strips but the inhibitory effect of
      dopamine was clearly more pronounced on electrically-induced tone. The effect of
      dopamine was not influenced by the presence of cocaine or hydrocortisone. The
      relaxant effect of dopamine, when tone was raised by methacholine, was not
      influenced by alpha- and dopamine receptor antagonists but it was significantly
      reduced by propranolol and ICI 118551 (erythro-DL-1-(7-methylindan-4-yloxy)-3-
      isopropylaminobutan-2-ol). The inhibitory effect of dopamine on the electrically
      induced tone was significantly reduced by phentolamine; domperidone tended to
      reduce the effect of the lower concentrations of dopamine. In the presence of
      propranolol, phentolamine and rauwolscine concentration-dependently antagonized
      the inhibitory effect of dopamine on electrically-induced tone, while prazosin
      was without influence. These results indicate that the inhibitory effect of
      dopamine in the cat gastric fundus is mainly due to interaction with
      postjunctional beta 2-adrenoceptors on the smooth muscle cells and with
      prejunctional alpha 2-adrenoceptors on the intramural cholinergic neurons.

PMID- 1355547
TI  - Selective inhibition of calcium entry induced by benzylisoquinolines in rat
      smooth muscle.
AB  - The mechanism of relaxant activity of six benzylisoquinolines was examined in
      order to determine the minimal structural requirements that enable these
      compounds to have either a non-specific action like papaverine or an inhibitory
      activity on calcium entry via potential-operated channels. All the alkaloids
      tested totally or partially relaxed KCl-depolarized rat uterus and inhibited
      oxytocin-induced rhythmic contractions. Only glaucine and laudanosine inhibited
      K(+)-induced uterine contractions more than oxytocin-induced uterine
      contractions. In Ca(+)-free medium, sustained contractions induced by oxytocin or
      vanadate were relaxed by the alkaloids tested except for glaucine and laudanosine
      indicating no inhibitory effect on intracellular calcium release. Those alkaloids
      containing an unsaturated heterocyclic ring (papaverine, papaverinol,
      papaveraldine, N-methylpapaverine and dehydropapaverine) exhibited a more
      specific activity than those with a tetrahydroisoquinoline ring.

PMID- 1355548
TI  - Effects of platelet activating factor on contractions and 45Ca influx induced by
      noradrenaline and potassium in rat rubbed and intact aorta. Comparison with its
      hypotensive effect in anaesthetized normotensive rats.
AB  - In order to clarify the mechanism of hypotensive activity of platelet activating
      factor (PAF), the effects of this drug on blood pressure in anaesthetized
      normotensive rats, on KCl- and noradrenaline-induced 45Ca uptake and contractile
      responses in rat aorta rings with and without endothelium were studied. PAF (3
      micrograms kg-1, i.v.) showed long-lasting hypotensive effects in anaesthetized
      normotensive rats accompanied by a significant increase in heart rate. PAF (0.1
      10 microM) did not relax the contractions induced by noradrenaline (10 microM) or
      K+ (60 mM) in rubbed or intact rat aorta. PAF did not affect the basal uptake of
      45Ca2+ nor that induced by the two vasoconstrictor agents. In experiments in a
      calcium free medium, PAF (10 microM) had no effect on the noradrenaline- (10
      microM) induced contractions. These results suggest that the hypotensive activity
      of PAF in normotensive anaesthetized rats is not due to a direct effect on rubbed
      and intact rat aorta rings (acting within the cell or blocking Ca2+ influx
      through L-type transmembrane calcium channels).

PMID- 1355549
TI  - Efficacy of verapamil against ventricular arrhythmias induced by programmed
      electrical stimulation in the late myocardial infarction phase in dogs.
AB  - The aim of the present study was to investigate the antiarrhythmic potential of
      verapamil in the late myocardial infarction period in conscious dogs. Verapamil
      was administered in cumulative doses (0.3 + 0.3 mg kg-1). The drug significantly
      lowered systolic and diastolic blood pressure after both doses. ECG signals
      showed short-lasting significant decrease in RR and QT intervals together with an
      increase in QTc interval. The parameters of the atrioventricular conduction
      system (PQ interval, 2:1 AV-conduction point) were significantly prolonged over
      the entire observation period. Ventricular effective refractory periods remained
      unaltered. In contrast to results obtained during acute ischaemia and in the
      first week thereafter, the present study demonstrates that verapamil moderately
      increases intraventricular conduction time 14 days after acute myocardial
      infarction. Verapamil prevented the induction of arrhythmias by programmed
      electrical stimulation (PES) in only 11% of all induction attempts. The lack of
      lengthening of refractory periods in the presence of a prolongation of
      intraventricular conduction time may be responsible for the poor antiarrhythmic
      efficacy. We conclude that verapamil is only of negligible value for the
      management of PES-induced ventricular arrhythmias in the late myocardial
      infarction period.

PMID- 1355550
TI  - Postoperative course of plasma protein binding of lignocaine, ropivacaine and
      bupivacaine in sheep.
AB  - The plasma protein binding of the 2,6-xylidide local anaesthetic agents
      lignocaine, ropivacaine and bupivacaine enantiomers was determined by equilibrium
      dialysis in plasma obtained from chronically catheterized sheep before and up to
      21 days after surgery. Three concentrations (1, 5 and 10 mg L-1), were used for
      each agent. Concentration-dependent binding was evident for each agent throughout
      the study period. R(+)-Bupivacaine was more extensively bound than S(-)
      bupivacaine at the higher concentrations. Compared with pre-surgery, binding of
      each agent was less on the first postoperative day but did not differ
      significantly from days 8 to 21.

PMID- 1355551
TI  - Stimulation of faecal excretion in rats by alpha 2-adrenergic antagonists.
AB  - The effects of several alpha-adrenoceptor antagonists on faecal output and water
      content in rats were investigated. Fed rats were treated either subcutaneously
      (s.c.) or orally with phentolamine, idazoxan, yohimbine, 1-(2-pyrimidinyl)
      piperazine (PmP) or prazosin. Drug potencies were compared on the basis of the
      dose inducing excretion of 1 g dry weight of faeces (AD1) by rats that do not
      normally excrete any faecal pellet during the observation time. The alpha 2
      antagonist, idazoxan (AD1 = 0.25 mg kg-1, s.c.) was approximately 2.5, 4 and 8
      times more potent than PmP, phentolamine and yohimbine in promoting faecal
      excretion. Prazosin, an alpha 1-antagonist with putative affinity for the alpha
      2B-receptor subtype, was the least effective (AD1 greater than 5 mg kg-1, s.c.).
      The same compounds also increased the water content of faeces and had similar
      potencies by the oral route. Both clonidine (0.15 mg kg-1, s.c.) and atropine
      (0.2 mg kg-1, s.c.) significantly prevented the effects of all antagonists on
      faecal excretion. The present results are consistent with the view that rat colon
      is under tonic inhibitory control of prejunctional alpha 2-adrenergic receptors,
      whose blockage by specific antagonists induces faecal excretion. The alpha 2A
      receptor subtype appears to be the most likely candidate for controlling faecal
      excretion through inhibition of acetylcholine release.

PMID- 1355552
TI  - The potent irritancy of the daphnane orthoester, resiniferatoxin, exhibits
      features of a mixed aetiology.
AB  - Resiniferatoxin-induced erythema of mouse ear was shown to possess
      characteristics of both a phorbol ester-mediated response and that induced by the
      neurogenic irritant, capsaicin. Whereas the response to the phorbol ester,
      sapintoxin D, was delayed and prolonged, and was augmented by capsaicin
      pretreatment, the response to resiniferatoxin was biphasic, with the early phase
      being antagonized by capsaicin desensitization. However, resiniferatoxin was most
      potent in inducing a delayed erythema which, unlike the capsaicin response, was
      sensitive to inhibition by low dose hydrocortisone treatment, but not to chronic
      capsaicin desensitization. It is concluded that the erythema response to
      resiniferatoxin has a mixed aetiology, which may explain the unique potency of
      this toxin.

PMID- 1355553
TI  - The cytoprotective effect of zinc L-carnosine on ethanol-induced gastric gland
      damage in rabbits.
AB  - The effects of zinc L-carnosine on the damaging actions of ethanol were examined
      in rabbit isolated gastric glands. Ethanol (8%, v/v) incubation produced a 50%
      viability of the gland populations and released a significant amount (38%) of the
      total lactate dehydrogenase (an index of membrane injury) of the glands. Zinc L
      carnosine pre-incubation for 15 min markedly prevented these actions of ethanol;
      however, L-carnosine by itself did not have these effects. The findings indicate
      that zinc ion but not carnosine in the zinc L-carnosine molecule possesses
      cytoprotective action against ethanol-induced gastric gland damage in rabbits.

PMID- 1355554
TI  - The effect of intravenous pretreatment with small liposomes on the
      pharmacokinetics and metabolism of antipyrine in rabbits.
AB  - The effect of intravenous pre-treatment with empty small liposomes on the
      pharmacokinetics and metabolism of antipyrine in rabbits has been investigated.
      The measured half-life of antipyrine was 104 min and the volume of distribution
      was 830 mL kg-1. The excretion of metabolites in a 24 h urine sample was
      measured, the main metabolite 4-hydroxyantipyrine was excreted to a level of 10%
      with the free drug accounting for 4%. The norantipyrine and 3
      hydroxymethylantipyrine metabolites were excreted to a level of 8 and 7%,
      respectively. The intravenous administration of liposomes at a dose equivalent to
      8 mg of egg yolk phosphatidylcholine daily for one week, had no significant
      effect on any of the measured pharmacokinetic parameters. The half-life after
      liposome treatment was 110 min and the volume of distribution was 790 mL kg-1,
      the metabolic pattern in the urine was also unaltered. The results suggest that
      the repeated administration of low doses of liposomes do not affect the
      pharmacokinetics and metabolism of antipyrine.

PMID- 1355555
TI  - An appreciation of the Folin-Lowry protein assay.

PMID- 1355556
TI  - Effect of CD4+ cell count measurement variability on staging HIV-1 infection.
AB  - A single CD4+ cell count (CD4) measurement is often used to stage HIV-1
      infection, decide when to initiate prophylactic therapy and inform patients, and
      may soon even define AIDS onset. Documentation of the reliability and validity of
      employing CD4 for the above purposes in a population-based setting is needed. We
      utilized data from 4,954 homosexual/bisexual men followed over 6 years, with CD4
      testing at 6 month intervals, to study the timing of CD4-based staging of HIV-1
      disease and quantify and evaluate the potential impact of CD4 measurement error.
      The median time from seroconversion to first CD4 test below 500 x 10(6)/L or
      clinical AIDS was 1.70 years, and the first CD4 test below 200 x 10(6)/L or
      clinical AIDs was 5.29 years. The time from first testing less than 500 x 10(6)/L
      to clinical AIDS in untreated men was 5.55 years. With confirmatory retesting,
      these times were significantly lengthened. The 95% confidence ranges for the true
      CD4 state in individuals with measured CD4 of 500 and 200 x 10(6)/L are at least
      (297 x 10(6), 841 x 10(6)/L) and (118 x 10(6), 337 x 10(6)/L), respectively.
      Without confirmatory retesting, individuals with true CD4 remaining at 700 x
      10(6) and 280 x 10(6)/L have at least a 40% chance for one of five CD4
      measurements to fall below guideline limits of 500 x 10(6) and 200 x 10(6)/L,
      respectively. Confirmatory retesting can reduce these probabilities to as low as
      4%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355557
TI  - Isolation of HIV-1 from plasma of infected individuals: an analysis of
      experimental conditions affecting successful virus propagation.
AB  - Experimental conditions affecting the successful propagation of HIV-1 from the
      plasma of seropositive individuals were examined. It was determined that whole
      blood samples collected with lithium heparin as the anticoagulant, immediate
      plasma separation, and immediate culturing were best suited for obtaining viable
      virus from plasma. Virus was isolated by infecting fresh phytohemagglutinin
      stimulated normal donor peripheral blood mononuclear cells (PBMCs) with plasma
      followed by weekly cocultivation with new target cells. The plasma virus
      isolation rate was the greatest and HIV-1 titers were the highest for those
      individuals with less than 200 CD4+ cells/mm3 and decreased as the level of CD4+
      cells approached normal values. We were able to obtain positive cultures from
      29.5% of those patients with CD4+ counts greater than 500/mm3. HIV-1 titers in
      plasma also correlated with high serum p24 antigen levels when serum was treated
      with glycine to dissociate antigen-antibody complexes.

PMID- 1355558
TI  - [Synthesis of metabolites of mosapramine. I. Synthesis of alcoholic metabolites].
AB  - Four alcoholic metabolites of (+-)-3-chloro-5-[3-(2-oxo-1,2,3,5,6,7,8,8a
      octahydroimidazo[1,2-a] pyridine-3-spiro-4'-peperidino)propyl]-10,11-dihydro-5'
      dibenz[b,f ] azepine(mosapramine), a new antipsychotic drug, were synthesized in
      order to determine their chemical structures. A mixture of 10-ethoxy-3-chloro
      10,11-dihydro-5H-dibenz[b,f]azepine and 11-ethoxy isomer was used as a starting
      material. Isomeric intermediates, i.e. 10-oxo-3-chloro-5-(3-chloropropyl)-10,11
      dihydro-5H-dibenz[b,f]azepine and 11-oxo isomer, were separated by chromatography
      with silica gel. The metabolites were obtained by NaBH4 reduction of the
      corresponding 10-oxo or 11-oxo compounds followed by introduction of spiro
      piperidine moieties into propyl side chain.

PMID- 1355559
TI  - Molecular diagnosis of Turner's syndrome.
AB  - Turner's syndrome is a common disorder which occurs in around 1/3000 live births
      in girls. Diagnostic use of polymorphic DNA markers for the X chromosome could
      help to reduce the number of time consuming karyotype analyses needed. The M27
      beta probe maps on the X chromosome to Xcen-Xp11-22 and in 83% of female subjects
      detects heterozygosity with multiallelic polymorphism. In Southern blotting, a
      single X chromosome yields a single hybridisation band. In this study, genomic
      DNA was extracted from leucocytes of 49 patients with Turner's syndrome
      (karyotypes: 45,XO, n = 29; 45,XO/46,XX, n = 4; 46,Xi(Xq), n = 1;
      45,XO/46,Xi(Xq), n = 4; 45,XO/46,Xr(X), n = 4; 45,XO/46,XY, n = 4; 46,XXp-, n =
      3), digested with EcoRI or HindIII, and analysed by Southern blotting. The
      molecular data for each patient were compared with DNA controls (homozygous
      46,XX, heterozygous 46,XX and 46,XY DNA). A single band of reduced intensity
      compared to homozygous 46,XX control DNA was seen in 41 cases. Two hybridisation
      bands of different intensities were seen in four patients, in one of whom
      mosaicism was suspected on the basis of molecular analysis, despite a 45,XO
      karyotype. In four cases, Turner's syndrome failed to be detected: one
      45,XO/46,XX mosaicism with only 4% of 45,XO cells and three distal Xp deletions.
      DNA analysis appears to be a useful and rapid tool in screening for Turner's
      syndrome and could be an alternative to cytogenetic analysis in diagnosing the
      disorder when severe growth retardation or delayed puberty are not accompanied by
      a Turner phenotype.

PMID- 1355560
TI  - Genetic mapping of X linked ocular albinism: linkage analysis in British
      families.
AB  - Genetic linkage studies were performed in 16 British families affected by X
      linked ocular albinism (XLOA) using RFLPs from the Xp22.3 region. Linkage was
      confirmed between the XLOA locus (OA1) and the loci DXS143 (dic56; Zmax = 15.90
      at theta = 0.0, confidence interval (CI) 0-0.035), DXS85 (782; Zmax = 15.67 at
      theta = 0.04, CI = 0.007-0.11), and DXS237 (GMGX9; Zmax = 12.65 at theta = 0.08,
      CI = 0.03-0.17). Multipoint linkage analysis placed OA1 between DXS85 (782) and
      DXS237 (GMGX9) with odds exceeding 10(4):1 to give the map DXS85-(OA1,DXS143)
      DXS237-XG-Xpter. OA1 lies close to DXS143 (dic56) but in the absence of
      recombinants the order of these loci could not be determined.

PMID- 1355561
TI  - Rapid detection of the highly polymorphic beta globin framework by denaturing
      gradient gel electrophoresis.

PMID- 1355562
TI  - Parental origin of extra chromosomes in persons with X chromosome tetrasomy.

PMID- 1355563
TI  - Further evidence that genotypically closely related strains of Legionella
      pneumophila can express different serogroup specific antigens.
AB  - The relationship between serogroup and genotype of Legionella pneumophila strains
      was investigated by restriction fragment length polymorphism (RFLP) typing with a
      previously standardised method. Of the 51 RFLP types identified, 19 comprised
      strains of more than one serogroup. Several RFLP types included strains of five
      or more serogroups. To determine if sharing the same RFLP type indicates that
      strains are genotypically indistinguishable or merely that they are superficially
      similar, 31 strains were selected for further analysis with an extended range of
      restriction endonucleases and nucleic acid probes. In some cases, strains of a
      particular RFLP type were indistinguishable, while in others the restriction
      fragment patterns showed minor differences. It is possible that in the latter
      case the strains are diverging representatives of a parent clone. We conclude
      that analysis of restriction fragment patterns, either probed or unprobed,
      provides a more accurate measure of the ancestral relationship between strains
      than can be obtained with serological methods.

PMID- 1355564
TI  - DNA restriction fragment length polymorphism differentiates recurrence from
      relapse in treatment failures of Streptococcus pyogenes pharyngitis.
AB  - In the evaluation of treatment failure in Streptococcus pyogenes pharyngitis it
      is necessary to distinguish between persistence of the original streptococcus and
      acquisition of a new strain. We used the analysis of restriction fragment length
      polymorphism (RFLP) of total DNA and of ribosomal DNA (rDNA) regions (ribotypes)
      as epidemiological tools to compare 43 pre- and post-treatment S. pyogenes
      strains obtained from 20 patients. In 16 cases pre- and post-treatment strains
      gave indistinguishable RFLP patterns of total DNA, strongly suggesting relapse
      with the same strain. However, in four cases different patterns were obtained for
      the pre- and post-treatment isolates, indicating recurrence due to the
      acquisition of a new strain. Ribotyping did not improve discrimination among
      strains. Thus, analysis of DNA RFLP is a promising method for distinguishing
      recurrence from relapse in failures of pharyngitis treatment.

PMID- 1355565
TI  - Typing of Australian methicillin-resistant Staphylococcus aureus strains by
      pulsed field gel electrophoresis.
AB  - Twenty-six clinical isolates of methicillin-resistant Staphylococcus aureus
      (MRSA) collected from six Australian hospitals by a National Staphylococcal Study
      Group were examined by analysis of restriction fragment length polymorphisms
      (RFLPs) of chromosomal DNA with pulsed field gel electrophoresis. Digestion with
      the restriction endonuclease SmaI produced 13-17 bands of 7-700 kb. The digestion
      patterns were easily distinguished and isolates could be classified into 17
      groups based on their RFLPs. Isolates giving a pattern associated with one group
      were from four hospitals in four different states. In another group, the isolates
      responsible were from three hospitals in two states and in a further group, the
      isolates were derived from two hospitals in different states. The remaining
      groups comprised only one member each. The method has promise for typing and
      studying the epidemiology of MRSA.

PMID- 1355566
TI  - Functional analysis of the intramolecular chaperone. Mutational hot spots in the
      subtilisin pro-peptide and a second-site suppressor mutation within the
      subtilisin molecule.
AB  - The N-terminal pro-peptide of 77 amino acid residues is essential for the folding
      of subtilisin, an alkaline serine protease from Bacillus subtilis. The synthetic
      pro-peptide has been shown to be capable of guiding the proper folding of
      denatured subtilisin to enzymatically active enzyme. Thus the pro-peptide serves
      as an intramolecular chaperone, which is removed by an autoprocessing reaction
      after the completion of the folding. With use of localized polymerase chain
      reaction random mutagenesis a total of 25 amino acid substitution mutations that
      affected subtilisin activities were isolated. These mutations occurred in a high
      frequency at the hydrophobic regions of the pro-peptide. For one of the
      mutations, M(-60)T, a second-site suppressor mutation, S(188)L, was isolated
      within the mature region. These results suggest that the pro-peptide consists of
      a few functional regions which interact with specific regions of the mature
      region of subtilisin during the folding process.

PMID- 1355567
TI  - Ecstasy-fueled 'rave' parties become dances of death for English youths.

PMID- 1355568
TI  - 'Rave' scene, ecstasy use, leap atlantic.

PMID- 1355569
TI  - [Flow cytometric measurement of cell surface and intracellular antigens present
      in leukemia cells].
AB  - Recent advances in flow cytometric technology has enabled us to perform
      multiparameter analysis of cell surface and intracellular antigens. The clinical
      application of such analyses requires to establish the procedures of sample
      preparation, fixation, staining, instrument calibration and data analysis. This
      article describes the basic elements involved in establishing such procedures and
      explores the use of multiparameter flow cytometric analysis in the
      characterization of human leukemia cells. Flow cytometric measurements of cell
      surface and intracellular antigens of leukemia cells can provide important
      insights into the biologic features of these cells as well as significant
      diagnostic information.

PMID- 1355570
TI  - [E2A gene in t(1;19)-ALL].
AB  - The t(1;19)(q23;p13) seen in approximately 5% of childhood acute lymphoblastic
      leukemia (ALL) has been reported to be associated with leukoencephalopathy. 1;19
      translocation can alter the E2A gene, leading to formation of a chimeric E2A-PBX1
      gene that retain the activator domain of the E2A gene but substitute a homeobox
      domain of the PBX1 gene for the helix-loop-helix DNA binding and dimerization
      domain of E2A. The translocation breakpoints occurs within a single intron of the
      E2A gene on chromosome 19, and interrupts a homeobox gene, PBX1, on chromosome
      1q23. Most cases with t(1;19) have been identified to have rearranged band of E2A
      by Southern blotting analysis, and to contain identical E2A-PBX1 chimeric
      transcripts by use of polymerase chain reaction assay. The molecular breakpoints
      in pre-B cases differ from those in early pre-B cases among t(1;19)-ALL. Thus,
      molecular analysis is useful for detection of t(1;19)-ALL.

PMID- 1355571
TI  - [Expression of multidrug resistance 1 and correlation with clinical drug
      resistance in acute leukemia].
AB  - Expression of multidrug resistance (mdr 1) gene, which encodes a transmembrane
      efflux pump referred to P-glycoprotein, leads to the decreased intracellular
      accumulation of various lipophilic drugs, such as vinca alkaloids, anthracyclines
      and epipodophyllotoxins. As these drugs are commonly used in chemotherapy for
      acute leukemia, it is of importance to determine whether mdr 1/P-glycoprotein
      expression is associated with clinical resistance. In several reports, some
      leukemia cells from untreated patients have expression of mdr 1/P-glycoprotein.
      We quantitatively detected low levels of mdr 1 expression in all cases of
      untreated acute leukemia and normal hematopoietic cells, using the reverse
      transcriptase-polymerase chain reaction. Carefully designed clinical trials
      including mdr 1 reversing agents may have significant consequences for the
      treatment of acute leukemia.

PMID- 1355572
TI  - [From a standpoint of psychiatry: effects of conditioned fear stress on
      monoaminergic systems in the rat brain].
AB  - The effects of electric footshock stress(EFS) and conditioned fear stress(CFS) on
      dopamine(DA) and serotonin(5-HT) metabolism in seven various brain regions of the
      rat were studied by measuring dihydroxyphenylacetic acid(DOPAC), homovanillic
      acid(HVA) and 5-hydroxyindoleacetic acid(5-HIAA). EFS for 30 min increased DOPAC
      and HVA levels in all seven brain regions and increased 5-HIAA levels in the
      medial prefrontal cortex(mPFC), nucleus accumbens and amygdala. CFS(exposure to
      an environment paired previously with footshock) increased plasma corticosterone
      levels and defecation, and induced freezing behavior. It also increased DOPAC
      levels in the mPFC, paraventricular nucleus of the hypothalamus and lateral
      hypothalamus, increased HVA levels in the mPFC and amygdala, and increased the 5
      HIAA level in the mPFC. In contrast to EFS, which increased DA and 5-HT
      metabolism in several other brain regions, increased metabolism of both DA and 5
      HT was especially marked in the mPFC after CFS. In this model, two classes of
      anxiolytics were examined for effects on freezing behavior. The benzodiazepine
      diazepam, a classical anxiolytic, reduced the freezing response. The new
      anxiolytic ipsapirone, a selective 5-HT1A agonist, also reduced the freezing
      response. These findings suggest the usefulness of this model for detecting the
      anxiolytic potential of drugs and examining the relation between 5-HT and
      anxiety.

PMID- 1355573
TI  - [Significance of anti-HTLV-I antibody in cerebrospinal fluid in diagnosis of HTLV
      I associated myelopathy (HAM)].
AB  - Anti-HTLV-I antibody was measured in 69 cerebrospinal fluids (CSFs) of cases with
      typical HTLV-I associated myelopathy (HAM) and other disorders whose symptoms
      were similar to HAM in order to evaluate the diagnostic significance of anti-HTLV
      I antibody in CSF. Both gelatin particle agglutination (PA; Serodia-ATLA) method
      and recombinant gag-env hybrid protein coated ELISA were employed simultaneously.
      Antibody titers of both methods showed linear correlation. Cases with typical HAM
      (24 cases) and HAM with additional neurological manifestations (7 cases) showed
      high positivity in both methods. Cases with other neurological disorders with
      possible HAM (11 cases, seropositive) and cases with other neurological disorders
      without HAM (12 cases, seropositive) showed low positivity with low titer in
      ELISA, on the other hand, 81% and 67% of those cases were positive in PA method.
      All cases with seronegative neuroimmunological disorders (15 cases) were negative
      in CSFs. These findings showed that anti-HTLV-I antibody in CSF is significant in
      diagnosis of HAM, and both PA and gag-env ELISA are useful to detect anti-HTLV-I
      antibodies in CSF.

PMID- 1355575
TI  - Relevance of mdr1 gene expression in acute myeloid leukemia and comparison of
      different diagnostic methods.
AB  - In an attempt to determine the incidence and clinical relevance of mdr1 gene
      expression in acute myeloid leukemia (AML), we examined 126 specimens obtained
      from adult patients with de novo AML by slot blot and immunocytochemistry. We
      found a high incidence of mdr1 gene expression in newly diagnosed patients (27%
      by immunocytochemistry and 43% by slot blot). No difference was observed between
      newly diagnosed patients and relapsed patients. However, patients with resistant
      disease showed statistically higher incidence of mdr1 gene expression compared to
      the untreated and relapsing patients (60% versus 27% by immunocytochemistry, p
      0.005; and 73% versus 45% by slot blot, p less than 0.05). The expression of mdr1
      gene correlated significantly with clinical drug resistance: 62% of patients
      positive for mdr1-mRNA and 68% of patients positive for P-glycoprotein (P-gp)
      eventually developed resistance to chemotherapy, while this was the case for a
      lower percentage of patients who did not express mdr1 gene (only 23% by slot blot
      analysis, p = 0.0052, or 24% by immunocytochemistry, p = 0.0009). A combined
      parameter, mdr1-mRNA/P-gp, had a very high prognostic value in terms of
      specificity and sensitivity. All nine patients (100%) who were mdr1-mRNA+/P-gp+
      progressed to clinical drug resistance afterward, whereas 11 of 13 (85%) patients
      who were mdr1-mRNA-1 P-gp- entered complete remission and only two patients later
      developed drug resistance (p = 0.0005). It could thus be used as a reliable
      parameter in clinical settings.

PMID- 1355574
TI  - Intercellular adhesion molecule-1 contributes to pulmonary oxygen toxicity in
      mice: role of leukocytes revised.
AB  - In immature or injured lungs, impaired alveolar gas exchange forces the use of
      elevated levels of inhaled oxygen to maintain life. But, at high concentrations
      oxygen induces lung injury, edema, and bronchopulmonary dysplasia, probably by
      stimulating the generation of reactive oxygen radicals and subsequent neutrophil
      infiltration. In addition to regulating neutrophil diapedesis, intercellular
      adhesion molecule-1 (ICAM-1) expression is marked on inflamed alveolar
      epithelium, suggesting a role for ICAM-1 in oxygen-induced, neutrophil-mediated
      parenchymal damage. To test this, we evaluated the rat anti-mouse ICAM-1
      monoclonal antibody YN1/1.7 in 2 protocols of oxygen-induced toxicity in adult,
      male Balb-c mice: greater than or equal to 95% O2 for 84 hr and greater than or
      equal to 95% O2 for 60 hr followed by 48 hr at 21% (ambient) O2. YN1/1.7
      treatment partially attenuated the neutrophil infiltration, lung damage (lavage
      lactate dehydrogenase [LDH] activity) and dysfunction (reductions in respiratory
      system compliance [Crs] and diffusion capacity of the lungs for carbon monoxide
      [DLCO] in the 84 hr exposure protocol. In the milder 60 hr exposure protocol,
      YN1/1.7 completely blocked the oxygen-induced lung dysfunction (reductions in Crs
      and DLco). These results confirm the contribution of leukocytes in the
      pathogenesis of pulmonary oxygen toxicity and indicate that antagonism of ICAM-1
      may provide a therapeutic approach to reducing hyperoxic lung injury and
      dysfunction.

PMID- 1355576
TI  - kappa-Opioid receptor stimulation increases intracellular free calcium in
      isolated rat ventricular myocytes.
AB  - The effect of two specific kappa-agonists, dynorphinA1-13 and U50,488H, on
      intracellular free calcium [Ca]i in isolated rat ventricular myocytes was
      studied. A spectrofluorimetric method using fura 2 as calcium indicator was
      employed. It was found that both agonists increased [Ca]i dose-dependently. The
      effect was attenuated by Mr 2266, a kappa-antagonist, indicating that the effect
      is a kappa-receptor mediated event. The effect was abolished by pretreatment with
      ryanodine, a drug that mobilizes calcium from the sarcoplasmic reticulum. It was,
      however, not affected by nifedipine, a calcium antagonist or removal of external
      calcium. The results indicate that the increase in [Ca]i due to kappa-opioid
      receptor stimulation results primarily from mobilization of calcium from an
      intracellular pool.

PMID- 1355577
TI  - Stereospecific effects of ascorbic acid and analogues on D1 and D2 agonist
      binding.
AB  - Ascorbic acid inhibited the specific binding of both the D1 agonist, [3H] SKF
      38393, and the D2 agonist, [3H] N-0437 at physiologically relevant
      concentrations. This inhibition was both stereospecific and receptor selective.
      Using ligand concentrations approximating their KD's, the IC50's for ascorbate
      and two structural analogues, isoascorbate and D-glucoascorbate, were determined.
      The rank order of IC50's at both D1 and D2 were D-glucoascorbate greater than
      isoascorbate greater than ascorbate. However, the IC50 for each compound was
      greater at D1 than D2. Evaluation of the relationship between the IC50 for
      ascorbate and the ligand concentration using both the D1 and the D2 ligand
      yielded data inconsistent with competitive inhibition models. Preliminary
      experiments were conducted to evaluate the site and type of inhibition with
      results consistent with an allostearic effect at the level of the receptor.

PMID- 1355578
TI  - Relationship between translocation of long-chain acyl-CoA hydrolase,
      phosphatidate phosphohydrolase and CTP:phosphocholine cytidylyltransferase and
      the synthesis of triglycerides and phosphatidylcholine in rat liver.
AB  - Translocation of long-chain acyl-coenzyme A hydrolase from the microsomal
      fraction to the cytosolic fraction was promoted in cell-free extracts of rat
      liver by palmitic acid, oleic acid, tetradecylthioacetic acid, and
      tetradecylthiopropionic acid, and by their CoA esters. The CoA esters were more
      effective than the non-esterified acids in the translocation of the enzyme.
      Treatment of normolipidemic rats with sulfur-substituted non-beta-oxidizable
      fatty acid analogues resulted in a transitory increase in hepatic concentration
      of long-chain acyl-CoA. Longer feeding times almost normalized the hepatic long
      chain acyl-CoA content. Microsomal long-chain acyl-CoA hydrolase activity was
      inhibited, whereas the activity of the cytosolic form was stimulated. The rise in
      enzyme activity coincided with a reduction in liver content of triglyceride and
      an increase in hepatic phospholipid content. The results suggest that the
      activity of long-chain acyl-CoA hydrolase in the cytosol may control the amount
      of acyl-CoA thioesters in the liver. Esterified and non-esterified fatty acids
      caused in vitro translocation of phosphatidate phosphohydrolase and cytidine 5'
      triphosphate (CTP):phosphocholine cytidylyltransferase from the cytosolic
      fraction to the microsomal fraction. However, the translocation of these two
      enzyme systems was not obtained in vivo. The activity of phosphatidate
      phosphohydrolase decreased in microsomal and cytosolic fractions while the
      activity of cytidylyltransferase in these fractions increased. The activities of
      soluble phosphatidate phosphohydrolase and long-chain acyl-CoA hydrolase appeared
      to be inversely correlated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355579
TI  - Toxoplasma encephalitis in patients with the acquired immunodeficiency syndrome.
AB  - Among 504 cases of AIDS diagnosed between 1983 and 1990, there were 86 patients
      (17%) with toxoplasma encephalitis (TE). All were symptomatic at the time of
      diagnosis. General signs such as fever, neck stiffness, or headache were present
      in 87.2%, and 75.6% had focal signs. The primary means of diagnosis was
      computerized tomographic scanning, revealing 169 lesions of which 80% were
      immediately contrast-enhancing. All patients had IgG antibodies against
      Toxoplasma gondii either before (74 of 75 evaluable patients) or at the time of
      diagnosis of TE (73 of 75). Elevated antibody titers were present in 44% of
      evaluable patients, compared to 11% of patients with AIDS and other opportunistic
      infections. Initial treatment was pyrimethamine plus sulfonamides in 65 patients,
      and pyrimethamine plus clindamycin in 12 patients, with other combinations or no
      treatment accounting for the remainder. Life-table analysis of the time to
      discontinuation of treatment because of suspected side effects suggested that
      sulfadiazine was significantly more toxic, with 48% of patients experiencing an
      interruption in treatment after 30 days, than pyrimethamine (12%) or clindamycin
      (24%). The 30-day mortality rate was 12%, and median survival was 310 days after
      diagnosis, 530 in patients treated with zidovudine and 190 days in those not so
      treated. Of 82 evaluable patients, 16 relapsed once and 4 of these more than
      once. The risk of relapse was 27% 1 year after diagnosis of a first episode of
      TE.

PMID- 1355580
TI  - Arginine abolishes the inhibitory effect of glucose on the growth hormone
      response to growth hormone-releasing hormone in man.
AB  - Acute hyperglycemia inhibits the growth hormone (GH) response to several stimuli
      including growth hormone-releasing hormone (GHRH), likely acting by stimulation
      of endogenous somatostatin release. The aim of our study was to verify whether
      arginine ([Arg] 30 g intravenously [IV] in 30 minutes), a well-known GH
      secretagogue likely acting via inhibition of hypothalamic somatostatin release,
      counteracts the inhibitory effect of oral glucose (OG) administration (100 mg
      orally) on the GH response to GHRH (1 micrograms/kg IV bolus) in seven normal
      subjects (aged 20 to 30 years). The GH response to GHRH (peak, 11.6 +/- 1.8
      micrograms/L) was inhibited by previous OG load (peak, 7.4 +/- 0.8 micrograms/L;
      P less than .02 v GHRH alone) and potentiated by Arg coadministration (peak, 36.2
      +/- 8.8 micrograms/L; P less than .03 v GHRH alone). The potentiating effect of
      Arg on the GHRH-induced GH increase was unaffected by previous OG load (peak,
      30.4 +/- 6.9 micrograms/L). In conclusion, our results show that Arg abolishes
      the inhibitory effect of OG administration on the GHRH-induced GH response in
      man. These data, although indirect, suggest that both acute hyperglycemia and Arg
      act at the hypothalamic level, stimulating and inhibiting, respectively, the
      release of somatostatin.

PMID- 1355581
TI  - Corticotropin-releasing hormone inhibition of paradoxical growth hormone response
      to thyrotropin-releasing hormone in insulin-dependent diabetics.
AB  - A paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH)
      has been observed in type 1 diabetic patients and was hypothetically attributed
      to a reduced hypothalamic somatostatin tone. We have previously reported that
      corticotropin-releasing hormone (CRH) inhibits GH response to growth hormone
      releasing hormone (GHRH) in normal subjects, possibly by an increased release of
      somatostatin. To study the effect of CRH on anomalous GH response to TRH, we
      tested with TRH (200 micrograms intravenously [IV]) and CRH (100 micrograms IV) +
      TRH (200 micrograms IV) 13 patients (six males and seven women) affected by
      insulin-dependent diabetes mellitus. A paradoxical GH response to TRH was
      observed in seven of 13 patients, one man and six women. In these subjects, the
      simultaneous administration of CRH and TRH significantly reduced the GH response
      to TRH, as assessed by both the maximal GH mean peak +/- SE (2.18 +/- 0.67 v 9.2
      +/- 1.26 micrograms/L, P less than 0.005) and the area under the curve (AUC) +/-
      SE (187 +/- 32 v 567 +/- 35 micrograms.min/L, P less than .001). CRH had no
      effect on TRH-induced thyroid-stimulating hormone (TSH) release. Our data
      demonstrate that the paradoxical GH response to TRH in patients with type 1
      diabetes mellitus is blocked by CRH administration. This CRH action may be due to
      an enhanced somatostatin release. Our data also show that exogenous CRH has no
      effect on TSH response to TRH, thus suggesting the existence of separate pathways
      in the neuroregulation of GH and TSH secretion.

PMID- 1355582
TI  - In vitro detection of somatostatin receptors in human tumors.
AB  - Somatostatin receptors (SSR) have been identified in membrane homogenates or
      tissue sections from several hundred human tumors. SSR have been found in most
      neuroendocrine tumors, ie, growth hormone (GH)- and thyrotropin (TSH)-producing
      pituitary tumors, endocrine gastroenteropancreatic (GEP) tumors, paragangliomas,
      pheochromocytomas, medullary thyroid carcinomas (MTC), and small-cell lung
      carcinomas. SSR have also been found in the majority of malignant lymphomas, in
      several brain tumors (all meningiomas, most astrocytomas), and in breast tumors.
      The majority of tumors expressing SSR are rather differentiated, eg, astrocytomas
      in contrast to glioblastomas, but exceptions such as high-grade malignant
      lymphomas do exist. An inverse relationship exists between SSR and receptors for
      epidermal growth factor in lung tumors, glial tumors, and most breast tumors,
      whereas meningiomas express both receptors simultaneously. A minority of tumors
      such as ovarian tumors, MTC, and insulinomas express a subtype of SSR
      characterized by low affinity for the octapeptide SS analogue, octreotide. The
      function of SSR in human tumors differs according to tumor type; SSR in pituitary
      and GEP tumors mediate hormone secretion inhibition and possibly have some
      antiproliferative effects. However, in meningiomas, activation of SSR inhibits
      forskolin-stimulated adenylate cyclase activity and weakly stimulates
      proliferation. Although SSR seem to mediate antiproliferative effects in animal
      models and cell lines of lymphomas and breast and lung tumors, such an effect has
      not yet been convincingly documented in human primary tumors.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1355583
TI  - Symposium: basic somatostatin research.

PMID- 1355584
TI  - The visualization of gastroenteropancreatic endocrine tumors.
AB  - In this review, we evaluate radiological techniques currently used to localize
      gastroenteropancreatic (GEP) endocrine tumors. We also describe the
      visualization, using intravenous (IV) administration of two isotope-labeled
      somatostatin analogues (123I-Tyr3-octreotide and 111In-DTPA-octreotide) of islet
      cell tumors in 25 patients and carcinoids in 39 patients. The primary tumor and
      previously unrecognized distant metastases were visualized in 20 of the 25
      patients (80%) and in 37 of the 39 patients (95%). Parallel in vitro detection of
      somatostatin receptors on those tumors also visualized in vivo showed that ligand
      binding to the tumor in vivo represents binding to specific somatostatin
      receptors. The detection of somatostatin receptors on tumors in vivo predicted a
      good suppressive effect of octreotide on hormonal hypersecretion by these tumors.
      It is an easy, quick, and harmless procedure that is valuable in the localization
      of primary endocrine pancreatic tumors and their often radiologically and
      clinically unrecognized metastases. Future prospective controlled studies
      comparing this procedure with other radiological investigative techniques should
      demonstrate its sensitivity and specificity and determine the place of
      somatostatin receptor imaging in the localization of GEP endocrine tumors.

PMID- 1355585
TI  - Potential role for somatostatin analogues in breast cancer: rationale and
      description of an ongoing trial.
AB  - Somatostatin analogues such as octreotide have been shown in experimental systems
      to exhibit antineoplastic activity. Further laboratory and clinical research is
      needed to clarify the mechanism of action of somatostatin analogues as
      antineoplastics, and to determine if the encouraging preclinical results will
      lead to novel endocrine approaches to the treatment of breast cancer.

PMID- 1355587
TI  - Somatostatin: the early days.

PMID- 1355588
TI  - Gallstones during octreotide therapy.
AB  - Gallbladder stones (GBS) are found in up to 50% of patients receiving octreotide,
      but the reported prevalence of cholecystolithiasis in patients treated with
      octreotide is variable and little is known about gallstone incidence,
      composition, pathogenetic mechanisms, dissolvability, and primary prevention.
      Octreotide treatment apart, in industrialised societies most GBS are mixed in
      composition, cholesterol-rich (arbitrarily greater than 70% cholesterol by
      weight), radiolucent (70%), and, given a patent cystic duct (70%), dissolvable in
      bile rendered unsaturated in cholesterol by oral ursodeoxycholic (UDCA) +/-
      chenodeoxycholic (CDCA) acid treatment. They form when (1) GB bile becomes
      supersaturated with cholesterol (as the molar ratio of cholesterol to
      phospholipids in biliary vesicles approaches 1:1, the vesicles become unstable);
      (2) there is an imbalance between pro- and anti-nucleating factors, which favors
      cholesterol crystal precipitation; and (3) there is stasis within the GB as a
      result of altered motor function and/or excess mucus that traps the crystals.
      These changes may be associated with altered (4) biliary bile acid composition
      (more DCA and less CDCA than normal), and/or (5) phospholipid fatty acid
      composition (arachidonyl-rich lecithin acting as a substrate for mucosal
      prostaglandin synthesis which, in turn, may influence both gallbladder motility,
      and mucus glycoprotein synthesis and secretion). During octreotide treatment,
      meal-stimulated cholecystokinin (CCK) release is impaired leading to GB
      hypomotility, but little is known about the effects of octreotide on biliary
      cholesterol saturation, crystal nucleation time, mucus glycoprotein
      concentration, bile acid or phospholipid fatty acid composition. Most, but not
      all, reports suggest that the prevalence of GBS in octreotide-treated patients is
      considerably greater than that in age-, sex-, and weight-matched controls, but
      proof (by pre-treatment and on-treatment ultrasound) that the GBS were absent
      before, but developed during, therapy is not always available. Furthermore, there
      are few data on analysis of GBS composition in patients developing stones during
      treatment, although initial reports suggest that octreotide-associated GBS are
      also radiolucent, cholesterol-rich, and dissolve with oral bile acid treatment.
      Maximum GBS attenuation values, measured in Hounsfield Units (HU) by localized
      computerized tomography scanning of the GB, predict stone composition and
      dissolvability: GBS with scores of less than 100 HU are cholesterol-rich and
      dissolve well with oral bile acid treatment. However, preliminary results in 11
      acromegalic patients treated with 200 to 600 micrograms octreotide/d for 29 to 68
      months show that the HU scores range from 23 to 490 (mean +/- SEM, 116 +/- 41),
      suggesting that at least four of these 11 patients have non-cholesterol
      stones.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1355589
TI  - From somatostatin to Sandostatin: history and chemistry.

PMID- 1355590
TI  - From somatostatin to sandostatin: pharmacodynamics and pharmacokinetics.
AB  - Somatostatin (SRIF) and its octapeptide analogue, octreotide (Sandostatin), have
      a similar high affinity for specific receptors with 50% inhibitory concentrations
      (IC50s) in the subnanomolar range. Hence, the striking superiority of octreotide
      in vivo, which includes duration of action, specificity, and potency, must
      originate from its different distribution, metabolism, and excretion behavior. In
      animals and humans, investigations of their pharmacodynamic/pharmacokinetic
      relationship show plasma levels of 0.2 to 0.5 ng/mL (approximately 0.3 nmol/L) to
      be therapeutically relevant for both peptides. The much lower clearance rates and
      improved metabolic stability in the circulation and in target organs of
      octreotide, compared with SRIF, result in much longer-lasting, therapeutically
      relevant plasma and tissue levels and therefore in a longer duration of action.
      Their apparently specific inhibitory action on growth hormone when compared with
      that on insulin is pharmacodynamically based, and may be exaggerated by
      physiological mechanisms of carbohydrate regulation. In summary, there is a
      distinct relationship between the pharmacokinetic profiles and pharmacodynamic
      behavior of SRIF and its analogue. Sandostatin.

PMID- 1355591
TI  - 111In-octreotide scintigraphy in oncology.
AB  - Various tumors of neuroendocrine origin that have amine precursor uptake and
      decarboxylation (APUD) characteristics can be visualized in vivo after
      intravenous (IV) injection of the somatostatin analogue, [123I-Tyr3]-octreotide.
      However, the relatively short effective half-life of this compound and the high
      background of radioactivity in the abdomen are drawbacks to its application.
      Therefore, an 111In-coupled somatostatin analogue ([111In-DTPA-D-Phe1]-
      octreotide) was developed. This analogue is excreted mainly via the kidneys, with
      90% of the dose being present in the urine 24 hours after injection. Using 111In
      octreotide scintigraphy, seven of seven gastrinomas, four of seven insulinomas,
      one of one glucagonomas, three of three unclassified APUDomas, and none of 18
      exocrine pancreatic carcinomas were visualized. Also, 19 of 19 carcinoids, 15 of
      15 glomus tumors, eight of 12 medullary thyroid carcinomas, six of six small-cell
      lung carcinomas, four of four growth hormone-producing and six of nine clinically
      nonfunctioning pituitary adenomas were visualized. Apart from APUD cell-derived
      tumors, 111In-octreotide scintigraphy was also successfully applied in
      visualizing breast cancer, lymphomas, and granulomas. In 39 of 50 patients with
      breast carcinoma, 10 of 11 patients with non-Hodgkin's lymphomas, three of three
      patients with Hodgkin's disease, and eight of eight patients with sarcoidosis,
      tumor sites accumulated radioactivity during octreotide scintigraphy. In a
      considerable number of patients with carcinoids and glomus tumors, and also in
      patients with granulomas and lymphomas, 111In-octreotide scintigraphy showed more
      tumor sites than did conventional imaging techniques. The results of imaging in
      vivo correlated with the somatostatin-receptor status on the tumors in
      vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355592
TI  - Pentostatin and 2-chlorodeoxyadenosine for hairy-cell leukemia.

PMID- 1355593
TI  - Effect of adrenergic agonists and antagonists on alanine amino transferase,
      fructose-1:6-bisphosphatase and glucose production in hepatocytes.
AB  - Using rat hepatocytes we confirmed our previous results that glucagon and beta
      adrenergic agonists increased the enzyme activity of alanine aminotransferase
      (AAT) and propranolol abolished their effects. Only the enzyme activity was
      measured and other parameters like quantity of the enzyme or activation due to
      modification were not looked for. As in perfusion experiment phenylephrine and
      phenoxybenzamine (alpha-agonist and alpha-antagonist respectively) also alpha
      antagonist respectively) also increased the AAT activity in isolated rat
      hepatocytes and propranolol reversed these effects. The additive effect of
      glucagon and phenoxybenzamine on AAT was also persistent in hepatocyte system.
      Fructose-1:6-bisphosphatase (Fru-P2-ase), another key enzyme in gluconeogenic
      pathway, was elevated by glucagon and other beta-adrenergic agonists both in
      liver perfusion and isolated hepatocyte experiments and was brought back to the
      normal level by propranolol. In this case also only the enzyme activity was
      measured and no other parameters were looked for. Unlike AAT this enzyme was not
      stimulated by phenylephrine or phenoxybenzamine. But AAT and Fru-P2-ase
      activities were increased significantly by adenylate cyclase activators like
      fluoride or forskolin. Thus, it appears that the regulation of fru-P2-ase by
      glucagon is purely a b-receptor mediated process whereas AAT activation shows a
      mixed type of regulation where some well known alpha-agonist and antagonists are
      behaving as beta-agonists. Results further indicate the presence of
      phosphodiesterase in hepatocyte membrane which was stimulated by glucagon and
      brought back to the normal level by propranolol. The different adrenergic
      compounds stated above, not only modified the activity of the above two enzymes
      but also stimulated glucose production by hepatocytes from alanine which was in
      turn abolished by propranolol as well as amino oxyacetate (AOA), a highly
      specified inhibitor of AAT. This confirm the participation of AAT in
      gluconeogenesis from alanine in liver. Forskolin and fluoride also increased the
      glucose production from alanine and showed additive effects with glucagon,
      phenylephrine and phenoxybenzamine.

PMID- 1355594
TI  - Management of atrial fibrillation.

PMID- 1355595
TI  - A comparison of electrophysiologically guided antiarrhythmic drug therapy with
      beta-blocker therapy in patients with symptomatic, sustained ventricular
      tachyarrhythmias.
AB  - BACKGROUND: Antiarrhythmic drug therapy guided by invasive electrophysiologic
      testing is now widely used in patients with symptomatic, sustained ventricular
      tachyarrhythmias. METHODS: We conducted a prospective, randomized trial in 170
      patients to investigate whether this approach would improve long-term outcome.
      Patients whose arrhythmia was inducible by programmed electrical stimulation were
      assigned to treatment with electrophysiologically guided drug therapy based on
      serial testing (61 patients) or with metoprolol (54 patients).
      Electrophysiologically guided therapy consisted of serial testing of
      antiarrhythmic agents to identify the first one that rendered the arrhythmia
      noninducible. The 55 patients whose arrhythmia was noninducible during the
      initial electrophysiologic test were also treated with metoprolol. RESULTS:
      During a mean (+/- SD) follow-up period of 23 +/- 17 months, recurrent, nonfatal
      arrhythmia occurred in 44 patients and sudden death due to cardiac factors in 27.
      The incidence of symptomatic arrhythmia and sudden death combined was virtually
      the same in the two groups with inducible arrhythmia after two years of
      observation (electrophysiologically guided therapy vs. metoprolol therapy, 46
      percent vs. 48 percent). The outcome was more favorable in the patients with
      noninducible arrhythmia at base line (75 percent had neither adverse event) than
      in those with inducible arrhythmia who were assigned to metoprolol therapy (P =
      0.009 by log-rank test). Only 6 of the 29 patients (21 percent) with inducible
      arrhythmia that became noninducible during drug therapy had recurrent arrhythmia
      or sudden death, as compared with 21 of the 32 patients (66 percent) with
      arrhythmia that continued to be inducible (P less than 0.001). A multivariate
      regression analysis identified continued inducibility of the arrhythmia as an
      independent predictor of recurrent arrhythmia or sudden death (relative risk,
      7.3; 95 percent confidence interval, 2.3 to 23.2; P less than 0.001).
      CONCLUSIONS: As compared with metoprolol therapy, electrophysiologically guided
      antiarrhythmic drug therapy did not improve the overall outcome of patients with
      sustained ventricular tachyarrhythmias. However, effective suppression of
      inducible arrhythmia by antiarrhythmic drugs was associated with a better outcome
      than was lack of suppression.

PMID- 1355596
TI  - Supraspinal administration of [D-Met2]FMRFamide produces a naloxone-sensitive
      increase in heart rate in unrestrained spontaneously hypertensive rats.
AB  - Intracerebroventricular (i.c.v.) administration of either Phe-Met-Arg-Phe-NH2
      (FMRFamide; molluscan cardioexcitatory neuropeptide; 3-30 micrograms) or the
      FMRFamide analog Phe-D-Met-Arg-Phe-NH2 ([D-Met2]FMRFamide; 15 micrograms) to
      conscious unrestrained spontaneously hypertensive rats (SHR) produced a
      relatively long lasting (greater than 1 h) increase in heart rate. The increase
      in heart rate produced by [D-Met2]FMRFamide was attenuated by i.c.v. injection of
      the opiate antagonist naloxone (2 micrograms). These results extend to a second
      endpoint an apparent opioid agonist-like (naloxone-reversible) action of [D
      Met2]FMRFamide.

PMID- 1355597
TI  - Human cytomegalovirus in rejected kidney grafts; detection by polymerase chain
      reaction.
AB  - Human cytomegalovirus (CMV) infections are frequently associated with graft
      rejection in the immunosuppressed patients following organ transplantation.
      Thirty-four tissue samples from rejected kidneys and 18 samples from normal adult
      kidneys obtained from autopsies were investigated for the presence of CMV-DNA by
      the polymerase chain reaction (PCR) and by immunohistochemistry. DNA extracted
      from renal tissues after proteinase K digestion was specifically amplified in 32
      cycles using primers which flank a 147 bp DNA fragment of the immediate early CMV
      gene and analysed by slot-blot hybridization with digoxigenin-labelled detection
      oligonucleotides. CMV-DNA was detected by PCR in a range from 0.1 fg up to 100 fg
      in 14 (41%) rejected kidney transplants. Comparative immunohistological analysis
      revealed presence of CMV in only three biopsies of these rejected kidneys.
      Furthermore, CMV-DNA was also found in four of 18 (22%) normal donor kidneys.
      These results reveal that CMV is often present in rejected kidneys and that the
      infection can be transferred from the donor to the recipient, since the normal
      adult kidney appears to be a frequent site of latency for CMV. No differences in
      local immunological changes, characterized by interstitial mononuclear leukocyte
      infiltration as well as by aberrant expression of HLA-class II antigens and of
      ICAM1 on proximal tubular epithelial cells, could be detected by further
      immunohistological analysis between grafted kidneys at late stage of rejection
      with and without CMV infection.

PMID- 1355598
TI  - [Agreements and discrepancies in radioiodine therapy of differentiated thyroid
      cancer. 2d Heidelberg Meeting of Nuclear Medicine Practitioners on 1.2.91].

PMID- 1355600
TI  - The post-myocardial infarction patient with hypertension. Long-term outcome.
AB  - Hypertension increases the risk of reinfarction and sudden death in post
      myocardial infarction (MI) patients. The same s true of coexisting left
      ventricular hypertrophy. Fortunately, these two risk factors may be modified by
      pharmacotherapy. In this article, Dr Boden describes the complementary use of
      beta blockers and selected calcium channel blockers for secondary prevention
      after acute MI, particularly in the subset of patients who also have
      hypertension.

PMID- 1355599
TI  - Comparative evaluation of the neuromuscular and cardiovascular effects of
      pipecuronium, pancuronium, atracurium, and vecuronium under isoflurane
      anesthesia.
AB  - The neuromuscular and cardiovascular effects of intubating doses of pipecuronium
      80 micrograms/kg, pancuronium 100 micrograms/kg, atracurium 500 micrograms/kg,
      and vecuronium 100 micrograms/kg were compared in 62 patients under isoflurane
      (end-tidal concentration = 0.5-1%) anesthesia. Pipecuronium, pancuronium, and
      vecuronium had no significant effect on systolic or diastolic blood pressure. In
      one patient the administration of atracurium resulted in significant hypotension.
      Heart rate was significantly increased only after the administration of
      pancuronium. The neuromuscular-blocking effect of pipecuronium and pancuronium
      appears to be twice as long as that of vecuronium and atracurium. Administration
      of neostigmine resulted in significantly faster recovery of muscle function in
      patients receiving vecuronium or atracurium. Although pipecuronium's
      neuromuscular-blocking effect is similar to that of pancuronium, its lack of
      cardiovascular effects more closely resembles that of vecuronium.

PMID- 1355601
TI  - Identification of a transcriptional repressor down-regulated during preadipocyte
      differentiation.
AB  - During differentiation of 3T3-L1 preadipocytes into adipocytes, the transcription
      of adipocyte genes, including the stearoyl-CoA desaturase 2 (SCD2) gene, is
      activated. Transfection experiments with chimeric SCD2 promoter-chloramphenicol
      acetyltransferase (CAT) reporter gene constructs revealed a preadipocyte
      repressor element (PRE) capable of repressing transcription of the reporter gene
      in preadipocytes but not in adipocytes. DNase I protection and gel retardation
      analyses were used to localize the PRE site between nucleotides -435 and -410 of
      the SCD2 promoter and to identify a nuclear PRE binding protein present at high
      levels in preadipocytes and HeLa cells but lacking or inactive in adipocytes.
      Southwestern blot analysis indicated that the PRE binding protein has an apparent
      molecular mass of approximately 58 kDa. A single copy of the PRE site, inserted
      upstream of the simian virus 40 enhancer/promoter of pSV2CAT, was capable of
      strongly repressing transcription of the reporter gene in preadipocytes and HeLa
      cells but not in adipocytes. Taken together these results suggest that the PRE
      site and binding protein may regulate transcription of SCD2 and possibly other
      adipocyte genes by inhibiting their transcription in preadipocytes.

PMID- 1355602
TI  - Superantigen staphylococcal enterotoxin B-induced T-helper cell activation is
      independent of CD4 molecules and phosphatidylinositol hydrolysis.
AB  - The role of the CD4 molecule in activation of T-helper cells was examined by
      investigating the effect of an anti-CD4 monoclonal antibody (Leu3a) in
      conventional peptide antigen-specific cloned T-helper cells that are also
      reactive to staphylococcal enterotoxin B (SEB). These T-helper cell clones are
      CD4+/CD45RO+/T-cell antigen receptor beta-chain variable region 12-positive and
      can respond to nominal peptide antigens and SEB by proliferation in the presence
      of class II major histocompatibility complex-expressing accessory cells. Although
      antigen and SEB were comparable in their ability to induce proliferative
      responses, interleukin 2 (IL-2) production, and IL-2 receptor alpha-chain
      expression, stimulation with SEB failed to trigger phosphatidylinositol
      hydrolysis or a rise in the intracellular free calcium ion concentration. Leu3a
      treatment inhibited antigen-induced proliferative responses of T cells with
      concomitant suppression of IL-2 production and IL-2 receptor expression. In
      contrast, SEB-induced responses were unaffected by Leu3a. These findings indicate
      that the functional consequences of binding (ligation) of conventional antigen
      and of superantigen with the T-cell receptor are distinct in the context of both
      signal transduction pathways and participation of CD4 molecules.

PMID- 1355604
TI  - Expression pattern of a murine homeobox gene, Dbx, displays extreme spatial
      restriction in embryonic forebrain and spinal cord.
AB  - Homeobox genes specify regional identity during development. A homeobox sequence
      that we have named Dbx was isolated from 13.5-day embryonic mouse telencephalon
      cDNA. The Dbx homeodomain shows highest sequence homology to Drosophila H2.0 and
      chicken CHox E. We report here the expression pattern of Dbx during mouse
      embryogenesis. In situ hybridization analyses indicate that Dbx is expressed
      exclusively within the embryonic central nervous system in a highly restricted
      manner. Dbx transcripts are detected within a region of the prospective cerebral
      cortex of the midgestation telencephalon. Dbx is also expressed in the
      diencephalon as well as in two thin continuous columns of neuroblasts within the
      hindbrain and spinal cord. This expression is limited to regions of active
      mitosis. Dbx may act to specify subsets of neuroblasts during the development of
      the central nervous system.

PMID- 1355603
TI  - Characterization of a metabotropic glutamate receptor: direct negative coupling
      to adenylyl cyclase and involvement of a pertussis toxin-sensitive G protein.
AB  - We have characterized a G-protein-coupled glutamate receptor in primary cultures
      of striatal neurons. Glutamate, quisqualate, or trans-1-aminocyclopentane-1,3
      dicarboxylate inhibited by 30-40% either forskolin-stimulated cAMP production in
      intact cells or forskolin plus vasoactive intestinal peptide-activated adenylyl
      cyclase assayed in neuronal membrane preparations. These inhibitory effects were
      suppressed after treatment of striatal neurons with Bordetella pertussis toxin,
      suggesting the involvement of a heterotrimeric guanine nucleotide-binding protein
      (G protein) of the G(i)/G(o) subtype. The pharmacological profile of this
      glutamate receptor negatively coupled to adenylyl cyclase was different from that
      of the metabotropic Qp glutamate receptor coupled to phospholipase C in striatal
      neurons and from that of the recently cloned "mGluR2" glutamate receptor, which
      is negatively coupled to adenylyl cyclase when expressed in non-neuronal cells.

PMID- 1355605
TI  - Endocytosis by antigen presenting cells: dendritic cells are as endocytically
      active as other antigen presenting cells.
AB  - Although dendritic cells are the most potent of all antigen presenting cells,
      they have paradoxically been regarded as having only a minimal capacity for
      endocytosis, which is a crucial step in antigen processing prior to presentation.
      Previous studies of dendritic cells, which are only available in small numbers,
      have been restricted to measurement of long-term endocytosis and so have stressed
      lysosomal accumulation. Measurement of traffic through late endosomes, which are
      closely related to the organelle in which antigen processing occurs, has, to
      date, required large numbers of cells and therefore has not been possible for
      dendritic cells. To resolve the paradox for dendritic cells, we have developed a
      flow cytometric assay of fluid-phase endocytosis that assesses late endosomal
      traffic by kinetic analysis of exocytosis in small numbers of cells. Using this
      assay, we show that fluid-phase endocytosis--in particular, traffic through late
      endosomes--is as active in dendritic cells as in other antigen presenting cells.

PMID- 1355607
TI  - Treatment strategies for daily life silent myocardial ischemia: a correlation
      with potential pathogenic mechanisms.
AB  - Recent investigations of SMI occurring during daily life have advanced our
      understanding of the pathophysiology of myocardial ischemia. These contributions
      have directed our attention away from "chest pain" alone and physical exertion as
      the central provoking factor toward transient myocardial ischemia and its broader
      triggers and consequences. Transient myocardial ischemic episodes, the majority
      of which are silent, are found in a subset of patients with any clinical
      manifestations of CAD (eg, stable angina, unstable angina, myocardial infarction,
      and sudden death), as well as in those patients with CAD who are and have been
      totally asymptomatic. These episodes are an independent predictor of increased
      risk for future cardiac events. Most medical therapy and revascularization
      therapies have the potential to prevent or relieve these silent episodes;
      however, we do not yet know which method is superior in reducing SMI episodes or
      preventing future cardiac events. Furthermore, the benefit of reducing SMI versus
      the cost and potential morbidity of these chosen therapies is not known. At least
      three trials are now underway to examine some of these concerns (Table 2). Focus
      on pain relief alone does not appear to be an adequate approach to alter outcome
      in patients with CAD and may prove insufficient to control SMI. Until these
      issues are resolved, we believe a conservative approach to the management of
      patients with CAD is warranted. Documentation of ischemia (painful or painless)
      is essential. Three general principles should be kept in mind. First, the
      presence of detectable ischemia is of central importance. This information should
      be used in the overall risk assessment of the patient. Second, the level of
      concern or aggressiveness of treatment should be based on the risk associated
      with the ischemic abnormalities documented (Table 3). The exercise stress test is
      the most useful to begin this process. The detection of ischemic-type ST-segment
      depression, either silent or painful, at a low workload (eg, less than or equal
      to 120 beats per minute or less than or equal to 6.5 metabolic equivalents
      [METS]) implies high risk for adverse outcome. Likewise, these ST-segment changes
      occurring in leads that reflect multiple coronary artery distribution, of greater
      than 2 mm in magnitude and persisting for greater than 6 minutes, are all markers
      for high risk. Thallium redistribution defects occurring at low work loads, in
      multiple areas, associated with increased lung uptake and enlargement of the
      cardiac pool all imply high risk.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1355608
TI  - Possible role of CD23 in allergic diseases.

PMID- 1355606
TI  - 3'-Azido-3'-deoxythymidine-induced reduction in the ability of uninfected CD4
      expressing cells to participate in syncytium formation.
AB  - A cocultivation assay system consisting of uninfected human T cells and cells
      chronically infected with human immunodeficiency virus type 1 has been used to
      investigate syncytium formation in short-term assays. Continuous treatment or
      short-term pretreatment of uninfected CD4-expressing human T-cell lines with 3'
      azido-3'-deoxythymidine (AZT) reduces the ability of these cells to participate
      in syncytium formation when mixed with chronically infected cells. The effect of
      AZT on syncytium formation is observed both as a reduction in the number of
      syncytia and as a reduction in the size of the syncytia that are detected. This
      syncytium-reducing effect of AZT is dose and time dependent and does not result
      from a modulation of CD4 antigen expression on the cell surface of uninfected,
      treated cells. Maximum syncytium reduction is observed with the continuous
      presence of AZT; however, pretreatment for times as short as 15 min results in a
      significant reduction in syncytium formation. Since reverse transcription is not
      required for efficient syncytium formation, the syncytium-reducing effect of AZT
      on uninfected human cells may represent an antiviral property of AZT with
      important therapeutic potential.

PMID- 1355609
TI  - Direct nucleotide sequencing using total cellular RNA from dengue-virus-infected
      mosquito cells.
AB  - In recent years, a large amount of nucleotide sequence data for dengue viruses
      has been published. Most of it was derived by sequencing cDNA synthesized from
      highly purified genomic viral RNA. This paper presents a simple and rapid method
      for the isolation of total RNA from mosquito cells infected with dengue viruses.
      This RNA can be used for direct nucleotide sequencing with specific primers
      without the need for further purification.

PMID- 1355610
TI  - A study of nephropathia epidemica among military personnel in Sweden.
AB  - The incidence of nephropathia epidemica (NE), caused by Puumala virus, among
      military troops operating in an endemic area of Sweden was investigated. A total
      of 705 soldiers (age 18-25) involved in field training in three different endemic
      counties were bled twice within a 6-month interval. Three individuals
      seroconverted when tested for Puumala virus antibodies by IgG ELISA. Symptoms
      typical of NE were not recorded in any of the patients. However, mild febrile
      episodes were recorded in 2 of the 3 individuals. One serologically confirmed
      soldier with typical NE symptoms was found in another group of 12,000 troops.
      This soldier fell ill 3 weeks after a 7-day-long field exercise. The present
      study indicates that military populations are at considerably greater risk of
      contracting NE when compared to the entire population residing in the same area.

PMID- 1355611
TI  - Qualitative shift of lymphokine production in response to stimulation, as a
      consequence of preactivation in vivo or in vitro.
AB  - Lymphokine production, analysed at the single cell level, was compared in resting
      and primed T-cell populations. Cells were preactivated in vitro by repeated
      mitogen stimulations, or isolated as large, low density cells naturally activated
      in vivo, from normal spleens of unimmunized animals. A similar qualitative shift
      in the pattern of lymphokines synthesized after restimulation was found as a
      result of in vivo and in vitro preactivation of cells. Repeated stimulations in
      vitro resulted in a qualitative shift in the lymphokines produced in response to
      activation, from a dominance of IL-2 during the first and second culture, to a
      dominance of IL-4 and IL-5 in the later stimulations. In vivo activation lead to
      a similar separation of lymphokine production as primarily IL-2 was made by small
      resting cells, while large cells preferentially produced IL-4 and IL-5. IFN-gamma
      was produced by both small and large cells. Preactivation in vitro lead to a more
      rapid appearance of lymphokines during restimulation. In contrast, the in vivo
      naturally activated cells responded with a slow onset of lymphokine production
      when stimulated in vitro.

PMID- 1355613
TI  - Antibodies to eukaryotic, including autologous, native DNA are produced during BK
      virus infection, but not after immunization with non-infectious BK DNA.
AB  - The contemporary view concerning the origin of anti-dsDNA antibodies is that
      eukaryotic dsDNA is not immunogenic. Results presented here, however, show (1)
      that inoculation of rabbits with BK virus elicits antibodies to eukaryotic,
      including autologous, dsDNA, (2) that the transition from a non-immunogenic to an
      immunogenic state of autologous dsDNA depends on productive infection with BK
      virus, and (3) that inoculation with protein-free circular BK dsDNA initiates
      both infection in vivo and production of antibodies to autologous dsDNA. Non
      infectious linearized BK dsDNA did not elicit any anti-dsDNA antibodies, while
      the same DNA molecule, when complexed with methylated bovine serum albumin,
      elicited anti-dsDNA antibodies solely recognizing BK dsDNA. Neither of the two
      linearized BK dsDNA preparations initiated infection. Using two different
      techniques, we could demonstrate that two separate sets of anti-dsDNA antibodies
      were produced during viral infection; one recognizing BK dsDNA, and the other
      recognizing autologous dsDNA. Thus, in contrast to previous assumptions,
      autologous dsDNA may be immunogenic. Based on the present results, we propose
      that autologous dsDNA can be rendered immunogenic through complex formation with
      viral DNA binding protein(s) such as the structural protein VP1 or the tumour
      antigen T. Such DNA-protein complexes may bypass a putative T-cell tolerance to
      autologous dsDNA.

PMID- 1355612
TI  - Activation of HLA-DR and interleukin-6 gene transcription in resting T cells via
      the CD2 molecule: relevance to chronic immune-mediated inflammation.
AB  - Only a minority of T cells at cell-mediated immune lesions are antigen specific.
      In the lesions of human autoimmune disease, such as the synovial membrane in
      rheumatoid arthritis, the T cells are activated as shown by a variety of
      phenotypic and functional changes including the expression of HLA-DR and the
      production of interleukin-6 (IL-6). The stimulatory pathway involved is unknown
      but does not seem to involve the T-cell receptor. Alternative pathways of
      activation which may be involved include the CD2 molecule. It is shown that the
      formation of sheep red blood cell (SRBC) rosettes with resting T cells from human
      peripheral blood, which is equivalent to CD2/LFA-3 binding, leads to the de novo
      transcription of the HLA-DR and IL-6 genes and the expression of HLA-DR on the
      surface of the T cells. There was no transcription of the interleukin-2 (IL-2) or
      the interleukin-2 receptor (IL-2R) genes and Tac expression was not seen. The
      rosetted T cells did not proliferate. These are all characteristics of T cells at
      chronic inflammatory sites. It is concluded that receptor-ligand interactions
      between CD2/LFA-3, which are expressed in increased amounts in the rheumatoid
      joint, may be one pathway by which antigen non-specific T cells are recruited as
      effector cells in lesions of human autoimmune disease.

PMID- 1355614
TI  - 24th Scandinavian Congress of Rheumatology. Malmo, Sweden, 31 May-3 June, 1992.
      Abstracts.

PMID- 1355615
TI  - Myopain '92. Abstracts from the 2nd World Congress on Myofascial Pain and
      Fibromyalgia. Copenhagen, Denmark, August 17-20, 1992.

PMID- 1355616
TI  - Protein oxidation and aging.
AB  - A number of systems that generate oxygen free radicals catalyze the oxidative
      modification of proteins. Such modifications mark enzymes for degradation by
      cytosolic neutral alkaline proteases. Protein oxidation contributes to the pool
      of damaged enzymes, which increases in size during aging and in various
      pathological states. The age-related increase in amounts of oxidized protein may
      reflect the age-dependent accumulation of unrepaired DNA damage that, in a random
      manner, affects the concentrations or activities of numerous factors that govern
      the rates of protein oxidation and the degradation of oxidized protein.

PMID- 1355617
TI  - XIIth International Conference on the Social Sciences and Medicine. Peebles,
      United Kingdom, September 14-18, 1992.

PMID- 1355618
TI  - Acute resistant asthma caused by excessive beta-2-adrenoceptor agonist inhalation
      and reversed by inhalation of beclomethasone.
AB  - With the aim of devising an improved beta 2-agonist treatment regimen for
      patients presenting with acute severe resistant asthma, a double-blind, placebo
      controlled randomised study of the effect of fenoterol and beclomethasone
      inhalations was done in 40 patients. Fenoterol inhalations had minimal effect in
      acute resistant asthma, but significant improvement was obtained when
      beclomethasone inhalations were given before fenoterol inhalations. Sequential
      beclomethasone and fenoterol inhalations can therefore be used as a preliminary
      emergency treatment for these patients.

PMID- 1355619
TI  - Tenth World Congress on Animal, Plant and Microbial toxins, Singapore. 3-8
      November 1991.

PMID- 1355620
TI  - Restriction fragment length polymorphism of the apoprotein A-I-C-III gene cluster
      in control and stroke-prone white and black subjects: racial differences.
AB  - BACKGROUND AND PURPOSE: The presence of known restriction fragment length
      polymorphisms in the apoprotein A-I-C-III gene cluster, which encodes their
      respective apoproteins, was investigated using the restriction enzymes Sac I and
      Pst I to determine the potential role of genetic variations for stroke risk in an
      American population. METHODS: Ninety-eight subjects (70 white, 28 black
      subjects), both normal controls with no carotid stenosis and those with carotid
      stenosis believed at risk for stroke, defined as showing stenosis focally or
      diffusely at that site, composed the study population. RESULTS: Sac I polymorphic
      S2 allele frequency was higher in stroke-risk groups, whereas Pst I polymorphic
      P2 allele frequency was similar in control and stroke-risk groups. Significantly
      higher levels of serum cholesterol, triglycerides, and low density lipoprotein (p
      less than 0.05) and significantly lower levels of high density lipoprotein (p
      less than 0.05) were observed in stroke-risk groups with diffuse stenosis.
      Results of our study with the two racial groups show the following: the frequency
      of Sac I polymorphism was significantly higher in American black compared with
      American white subjects (chi 2 = 3.92, p less than 0.05). Among serum lipids,
      triglycerides were significantly higher in white compared with black subjects (p
      less than 0.05). In white subjects, carotid artery stenosis was associated with
      significantly elevated total cholesterol and low density lipoprotein (p less than
      0.01) but not with Sac I polymorphism. In black subjects the converse was
      observed, namely, the Sac I polymorphic S2 allele seemed to be associated with
      carotid bifurcation stenosis but did not reach statistical significance because
      of the small number of subjects. In addition, Sac I polymorphism did not
      correlate with any lipid profile. Pst I polymorphism was not associated with any
      lipid profile or carotid artery stenosis abnormalities. CONCLUSIONS: Our results
      indicate that carotid artery stenosis identifies white subjects with increased
      plasma total cholesterol and low density lipoprotein, an atherogenic profile, but
      not with Sac I polymorphism. These findings suggest that carotid bifurcation
      stenosis in white subjects is associated with an atherogenic lipid profile but
      not with apoprotein A-I-C-III restriction fragment length polymorphisms. In black
      subjects, Sac I polymorphism seems to identify those individuals with significant
      carotid stenosis, a necessary precursor to atherothrombotic brain infarction, but
      not those with elevated total cholesterol, elevated low density lipoprotein,
      and/or reduced high density lipoprotein. These results suggest that Sac I
      polymorphism may identify black subjects at increased risk for atherothrombotic
      brain infarctions.

PMID- 1355621
TI  - Fibrin glue from single-donation autologous plasmapheresis.
AB  - A method is described for preparing fibrin glue from fibrinogen obtained by
      double cryoprecipitation of plasma collected by plasmapheresis. Plasma (average
      volume, 528.8 +/- 86 mL), collected from 12 plasmapheresis donors was
      cryoprecipitated twice. When the cryoprecipitated pellet was resuspended in 0.5
      to 2 mL of saline (total volume of saline-resuspended fibrinogen: 5 mL), the
      average yield of fibrinogen was 78.4 +/- 18.3 mg per mL. This is comparable to
      commercial preparations, is suitable for clinical use, and offers greater safety
      at a reduced cost.

PMID- 1355622
TI  - Analysis of the gene polymorphism of ABO blood group specific transferases helps
      diagnosis of acquired B status.
AB  - Blood group typing of an aged patient suffering from ileus provided evidence for
      an acquired B. As a parameter independent of cell membrane molecules or secreted
      blood group substances, the nucleotide sequence polymorphism of A and B
      transferases was investigated. Restriction fragment length polymorphism of DNA
      chains amplified in a polymerase chain reaction from the coding region of the
      glycosyltransferase indicated that no gene for B transferase was present in the
      patient's genome. We conclude that the assessment of polymorphism of AB0 blood
      group transferase can be used as a marker independent of blood group molecules
      for confirming a suspected acquired B.

PMID- 1355624
TI  - 4th Thyroid Symposium. Brain and Thyroid. Graz, Austria, May 6-9, 1992.

PMID- 1355623
TI  - Degradation of oxytocin by the human placenta: effect of selective inhibitors.
AB  - The hydrolysis of oxytocin by human placental subcellular fractions was studied
      in the presence of selective inhibitors by measuring liberated amino acids by
      high performance liquid chromatography (HPLC). Oxytocin degradation by microsomal
      and lysosomal fractions was inhibited by bestatin, amastatin and puromycin. The
      IC50 values of these inhibitors on oxytocin degradation by both fractions were
      similar to those of these inhibitors on the human placental aminopeptidase M
      measured by L-Leu-p-nitroanilide as a substrate (LAP activity), which we reported
      previously. However, purified aminopeptidase M from human placental microsomal
      fractions could not liberate any amino acid from oxytocin. Since phosphoramidon
      (1 mumol/l), a putative metalloendopeptidase inhibitor, and N-benzylcarbonyl
      valyl-prolinal (Z-Val-prolinal) (14 mumol/l), a selective inhibitor of post
      proline endopeptidase, could not significantly influence the degradation of
      oxytocin by either subcellular fractions, neither enzyme seems to be actively
      involved in oxytocin degradation. These results strongly suggested the existence
      of oxytocinase(s) other than the above three enzymes in microsomal and/or
      lysosomal fractions of human placenta.

PMID- 1355625
TI  - Abstracts of the 4th Northern Lights Neuroscience Symposium: Pathobiology of
      Mental Retardation, annual meeting. Gothenburg, Sweden, September 12-14, 1991.

PMID- 1355626
TI  - Actions of serotonin antagonists on cholera-toxin-induced intestinal fluid
      secretion.
AB  - The effects of several 5-hydroxytryptamine (5-HT) receptor antagonists were
      tested in rats in vivo on the intestinal fluid secretion evoked by cholera toxin.
      Five receptor antagonists were used, namely 2-bromolysergic acid diethylamine (2
      bromo-LSD), granisetron, ketanserin, methysergide and ondansetron. The drugs were
      used in doses that inhibited the arterial hypertension and/or bradycardia evoked
      by 5-HT given i.v. Granisetron and ondansetron markedly diminished cholera-toxin
      evoked secretion, whereas ketanserin was without any effect. Methysergide also
      diminished cholera-toxin-induced fluid secretion particularly when the drug was
      given as an i.v. infusion. The results are considered in relation to the
      pathophysiology of cholera secretion and to the current views of receptor
      subtypes for 5-HT. It is proposed that the receptor involved is a 5-HT3 receptor,
      possibly also a receptor of the 5-HT1 type. Results from experiments in which 5
      HT (20 mM) was placed in the intestinal lumen to evoke an intestinal secretion
      suggest that the 5-HT3 receptor is located in the villus tissue. It was also
      demonstrated that zimeldine, an inhibitor of presynaptic 5-HT reuptake,
      diminished choleraic secretion, an effect that may be ascribed to a 5-HT
      tachyphylaxis caused by an accumulation of 5-HT in a synaptic cleft.

PMID- 1355627
TI  - c-erbA: protooncogene or growth suppressor gene?

PMID- 1355628
TI  - [Immunochemical detection of the proliferating cell nuclear antigen (PCNA/cyclin)
      in ocular tissues].
AB  - The authors developed radioimmunoassay (RIA) for proliferating cell nuclear
      antigen (PCNA/cyclin), which a protein synthesizes in phase with DNA, as a marker
      for cell replication. We used it to detect the amounts of PCNA and estimated
      rates of cell replication in ocular tissues (cornea, lens epithelium, retina-plus
      choroid and optic nerve) and in non-ocular tissues (skin, skeletal muscle, brain,
      thymus, small intestine and liver) in rats. Antisera were raised in rabbits to
      oligopeptide fragment of human PCNA (hPCNA): the C-terminal fragment [Tyr254]
      hPCNA (254-261). For RIA the synthetic peptides were used as standards and
      radioiodinated [125I-Tyr254]-hPCNA (254-261) as radioligands. The IC50 was 30-40
      f mole/tube with a sensitivity 0.5-1.0 f mole/tube for this assay. Tissue
      extracts in 1 M acetic acid were digested with trypsin to release fragment (255
      261) from whole PCNA and were assayed by this method. The highest amounts of
      immunoreactive PCNA were found in lens epithelium and skin, while the lowest
      amounts were found in optic nerve and muscle. The cornea showed a higher value
      than retina-plus-choroid or optic nerve. A high cell replication in the lens
      epithelium was revealed.

PMID- 1355629
TI  - Effect of beta-adrenoceptor blockade on dipyridamole-induced myocardial
      asynergies in coronary artery disease.
AB  - Twenty-one patients with angiographic evidence of significant coronary artery
      disease, and positive dipyridamole echocardiographic test results at basal
      condition and after 7 days of placebo treatment were prospectively studied to see
      whether beta blockade modifies the effects of dipyridamole echocardiographic
      testing on regional myocardial contractility. Patients were randomized to
      propranolol (120 mg/day) or placebo treatment in 3 divided doses for 7 days,
      after which each patient crossed over to the alternate regimen. Dipyridamole
      echocardiographic testing was repeated at the end of each treatment. Propranolol
      abolished new mechanical signs of transient dipyridamole-induced ischemia (new
      wall motion abnormalities or an increase in degree of basal asynergies, or both)
      in 13 of 21 patients. The remaining 8 patients had positive results on
      dipyridamole echocardiographic testing after the propranolol treatment period. At
      basal conditions both heart rate and rate-pressure product were significantly
      reduced with propranolol; there was also a significant decrease in these
      parameters at peak dipyridamole infusion. At peak dipyridamole infusion heart
      rate and rate-pressure product were significantly lower in patients with negative
      than in those with positive echocardiographic test results after propranolol. Our
      data show that administration of beta blockade significantly reduces the
      development of transient dipyridamole-induced myocardial asynergies, the earliest
      markers of acute myocardial ischemia, detected with 2-dimensional
      echocardiography.

PMID- 1355630
TI  - Deletion of the Hunter gene and both DXS466 and DXS304 in a patient with
      mucopolysaccharidosis type II.
AB  - Hunter syndrome is an X-linked mucopolysaccharidosis due to deficiency of the
      lysosomal enzyme iduronate-2-sulfatase (IDS). A cDNA clone containing the entire
      coding region of the human IDS gene, mapped in Xq28, has been used as molecular
      probe to study a patient with Hunter syndrome. A submicroscopic deletion has been
      detected that spans the IDS gene as well as DXS466 and DXS304, 2 loci mapped
      probably not more than 900 kb from the IDS locus. A detailed clinical description
      of the patient is provided and his phenotype is compared to that of other
      patients with IDS deletion described recently. By following the segregation of a
      restriction fragment length polymorphism at the IDS locus in the patient's
      family, our data suggest that the deletion occurred in the germ cells of the
      patient's grandfather.

PMID- 1355631
TI  - Parental origin of the X chromosomes in Rett syndrome.

PMID- 1355632
TI  - First prenatal diagnosis of X-linked lymphoproliferative disease.
AB  - A family study was performed in order to diagnose X-linked lymphoproliferative
      (XLP) disease in a fetus. The molecular genetic analysis indicated that the
      fetus, as well as its healthy 7-year-old brother, inherited XLP. Analysis of
      immunoglobulin subclasses from the 7-year-old brother supported the DNA-based
      diagnosis. This is the first XLP family of African descent.

PMID- 1355634
TI  - An overdose of ecstasy. A role for dantrolene.
AB  - An overdose of the semisynthetic, hallucinogenic amphetamine 3,4
      methylenedioxymethamphetamine resulted in convulsions, hyperthermia,
      hyperkalaemia and rhabdomyolysis. The patient's management, which included the
      use of dantrolene, is discussed.

PMID- 1355633
TI  - Dexamethasone prevents autoimmune nephritis and reduces renal expression of Ia
      but not costimulatory signals.
AB  - Although glucocorticoids are a conventional treatment for lupus nephritis, the
      cellular and molecular mechanisms responsible for preventing renal injury are
      unknown. MRL-lpr mice develop an aggressive autoimmune nephritis. As these mice
      become nephritic, there is an increase in the renal expression of molecules that
      permit or facilitate immune interactions, including MHC class II (Ia) antigens,
      intercellular adhesion molecule-1 (ICAM-1), and pro-inflammatory cytokines.
      Because dexamethasone (Dex) alters Ia antigen expression and suppresses cytokine
      generation, the authors prophylactically treated MRL-lpr mice and investigated
      the relative importance of these molecules in inducing renal injury. MRL-lpr mice
      given Dex (0.4 mg/kg/d) from age 6 weeks were killed 4, 8, and 16 weeks after the
      initiation of therapy, and tissue was removed for histology and extraction of
      total RNA. Dex prevented lymphadenopathy and renal injury. DEX eliminated the
      marked Thy 1.2+ lymphocytic infiltrates within the kidney and preserved normal
      renal histology and urinary protein levels. Northern blot analysis of steady
      state mRNA transcripts indicated Dex suppressed a four-fold increase in kidney
      major histo-compatibility complex class II (Ia) molecule antigen mRNA seen by age
      22 weeks (Ia/beta-actin ratios = 0.64 +/- 0.50 versus 2.32 +/- 0.48, P less than
      0.01), but did not alter the costimulatory molecules ICAM-1 or tumor necrosis
      factor alpha (TNF alpha). Although all of these molecules are important mediators
      of inflammation, autoimmune nephritis was ameliorated without alteration of TNF
      alpha gene transcription or ICAM-1 transcription and surface expression. This
      study suggests that the benefit of steroids in nephritis stems from preventing
      lymphocyte infiltration into the kidney and decreasing immune interactions by
      limiting Ia expression.

PMID- 1355635
TI  - Riboflavin 5'-pyrophosphate: a contaminant of commercial FAD, a coenzyme for FAD
      dependent oxidases, and an inhibitor of FAD synthetase.
AB  - Commercially available preparations of flavin adenine dinucleotide (FAD) have
      been found to be 94% pure, the remaining 6% being composed of four or five minor
      contaminants which can be separated from FAD by reverse-phase high-performance
      liquid chromatography. FAD purified in this manner has been shown to be 100%
      pure. One of the contaminants has been identified as riboflavin 5'-pyrophosphate
      (RPP) by spectroscopic and chemical methods of analysis. This compound has been
      shown to exhibit biological activity as a weak cofactor for two FAD-requiring
      enzymes. With the apoprotein of porcine D-amino-acid oxidase, values determined
      for RPP were 8.4 microM for Km and 0.10 for Vmax compared to 0.47 microM and 0.28
      (36 U/mg), respectively, for FAD. With fungal glucose apooxidase, values
      determined for RPP were 474 nM for Km and 0.02 for Vmax and 45 nM and 0.09 (105
      U/mg), respectively, for FAD. RPP can also inhibit FAD biosynthesis. For bovine
      liver FAD synthetase, a Ki value for RPP against FMN was determined to be 9
      microM where Km for FMN was 5.5 microM. These studies illustrate the value of
      riboflavin 5'-pyrophosphate as a flavin analog for use in the study of
      structure/function relationships within certain flavin-dependent enzymes.

PMID- 1355636
TI  - Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during
      and after upper abdominal surgery.
AB  - There is currently accumulating evidence for bidirectional communication between
      the neuroendocrine and immune systems. Various cytokines have been suggested to
      be involved in the stimulation of stress hormone secretion during the times of
      infection and inflammation. To assess the possible involvement and
      pathophysiologic significance of cytokines in the mechanisms responsible for the
      perioperative stress response of the hypothalamo-pituitary-adrenal axis, we
      observed the changes of plasma adrenocorticotropic hormone and cortisol levels
      together with those of plasma endotoxin and cytokine levels. In patients
      undergoing pancreatoduodenectomy, perioperative stimulation of
      adrenocorticotropic hormone and cortisol secretion was accompanied by a
      significant elevation of plasma cytokine levels. Application of epidural block up
      to the upper thoracic levels failed to suppress this stress response effectively.
      In patients undergoing unilateral total hip replacement, the response of plasma
      hormone levels was smaller and briefer with no significant increase of plasma
      cytokine levels. Application of epidural block up to the lower thoracic levels
      suppressed this hormonal response almost completely. In patients undergoing
      pancreatoduodenectomy, a significant elevation of plasma endotoxin level was
      followed by a gradual but significant elevation of plasma tumor necrosis factor
      alpha and interleukin-6 levels. It seems likely that the stimulatory effects of
      these cytokines on the secretion of adrenocorticotropic hormone and cortisol
      might be involved in the development of the greater and more prolonged stress
      response of hypothalamo-pituitary-adrenal axis. Our present study suggests that
      not only neural input from the surgical wound but also stimulation of cytokine
      production were responsible for the development of the stress response of the
      hypothalamo-pituitary-adrenal axis during and after upper abdominal
      surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355637
TI  - Role of guanylate cyclase-cGMP systems in halothane-induced vasodilation in
      canine cerebral arteries.
AB  - The cellular mechanisms through which halothane dilates blood vessels remain
      largely unknown. The present studies were designed to determine the effects of
      0.59 and 0.9 mM halothane (equivalent to 2.0% and 3.0%, respectively) on tissue
      cyclic guanosine 3,5-monophosphate (cGMP) level and guanylate cyclase enzyme
      activity in canine middle cerebral arteries. Rings of cerebral arteries
      preconstricted with 5-hydroxytryptamine (0.2 microM) were exposed for 15 min to
      low or high concentrations of halothane or for 5 min to sodium nitroprusside (50
      microM). The vessels were instantaneously frozen by immersing them in liquid N2;
      they then were homogenized, and the tissue cGMP levels were determined using
      radioimmunoassay. Halothane produced 2.23 +/- 0.44- and 4.47 +/- 0.87-fold
      increases in tissue cGMP levels over control at 0.59 and 0.9 mM, respectively.
      Sodium nitroprusside, a nitrovasodilator, also increased the tissue cGMP level
      7.80 +/- 1.36-fold over the control value. To understand better the mechanisms of
      halothane-induced increase of tissue cGMP level, the effects of this anesthetic
      agent on guanylate cyclase enzyme activity were examined. Halothane, unlike
      sodium nitroprusside, did not modulate the activity of the soluble guanylate
      cyclase enzyme. However, halothane (1.0 mM), like atrial natriuretic factor (5
      microM), stimulated the particulate guanylate cyclase enzyme activity. LY-83583
      (6-anilino-5,8-quinolinedione, 10 microM), an agent that inhibits soluble
      guanylate cyclase activity, significantly reduced the response of the vessels to
      calcium ionophore (A23187, 0.4 microM), an endothelium-dependent vasodilator,
      without producing a significant effect on halothane-induced vasodilation. These
      results suggest that halothane-induced vasodilation of cerebral blood vessels is
      partly mediated by an increase in tissue cGMP levels.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1355638
TI  - Intrathecal clonidine and the response to hemorrhage.
AB  - Intraspinally administered alpha 2-adrenergic agonists are being examined for
      postoperative analgesia, yet their effects on the hemodynamic response to acute
      hemorrhage have not been examined. In this study chronically prepared conscious
      sheep received thoracic intrathecal saline or clonidine 300 micrograms followed
      in 15 min by rapid removal of 1,000 ml blood. In saline-treated ewes blood
      pressure was maintained and heart rate steadily increased during hemorrhage of up
      to 700 ml blood, with further blood removal resulting in rapid decreases in both
      variables. In contrast, heart rate never increased and blood pressure was
      maintained only up to 400 ml blood loss in animals receiving intrathecal
      clonidine. Compared to saline controls, clonidine did not alter blood pressure or
      heart rate at the end of hemorrhage or during blood pressure restitution during
      the next hour. Clonidine inhibited the increase in plasma epinephrine at the end
      of hemorrhage without altering plasma norepinephrine, vasopressin, renin, or
      atrial natriuretic factor. Intrathecal idazoxan, a specific alpha 2-adrenergic
      antagonist, reversed clonidine's effect on blood pressure during hemorrhage.
      Intravenous DG-5128, a poorly lipid-soluble alpha 2-adrenergic antagonist, also
      reversed clonidine's effect and additionally completely blocked any reduction in
      blood pressure and heart rate during hemorrhage. These data suggest that
      intrathecal clonidine interferes with maintenance of blood pressure during
      hemorrhage, likely because of a spinal sympatholytic effect, but does not affect
      the ultimate decrease in blood pressure after rapid removal of 1,000 ml blood.
      This difference in effect during the two phases of hemorrhage can be explained by
      the relative importance of the sympathetic nervous system in each.

PMID- 1355639
TI  - Premedication with oral dexmedetomidine alters hemodynamic actions of intravenous
      anesthetic agents in chronically instrumented dogs.
AB  - Dexmedetomidine (the D-stereoisomer of medetomidine), a highly selective alpha 2
      adrenoceptor agonist, has been demonstrated to produce analgesia and sedation and
      attenuate hemodynamic responses to emergence from inhalational anesthetics, which
      suggests a potential use for this drug as a premedicant for general anesthesia.
      The authors examined hemodynamic interactions between dexmedetomidine and three
      commonly used intravenous anesthetic agents with markedly different hemodynamic
      effects. Conscious, chronically instrumented dogs received intravenous induction
      doses of ketamine, propofol, or etomidate, followed by continuous infusions of
      each drug at four different doses for 15-min intervals on different days. Studies
      in six separate groups (range, 9-12 dogs/group) with and without pretreatment
      with oral dexmedetomidine (20 micrograms/kg) were completed. Heart rate, arterial
      pressure, left ventricular pressure, rate of increase of left ventricular
      pressure at 50 mmHg (dP/dt50), and cardiac output were continuously recorded.
      Dexmedetomidine administration caused a significant (P less than 0.05) decrease
      in heart rate, rate-pressure product, left ventricular dP/dt50, and cardiac
      output. Dexmedetomidine abolished or attenuated the increase in heart rate, rate
      pressure product, cardiac output, and arterial pressure produced during induction
      of anesthesia with ketamine. After the dexmedetomidine pretreatment, continuous
      infusion of ketamine caused no increase in heart rate or rate-pressure product.
      However, ketamine significantly reduced left ventricular dP/dt50 compared to
      control in dogs premedicated with dexmedetomidine. Except for a significant
      reduction in systemic vascular resistance, dexmedetomidine did not significantly
      affect the hemodynamic response to induction of anesthesia with propofol.
      Similarly, dexmedetomidine did little to alter the hemodynamic response to
      induction of anesthesia with etomidate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355640
TI  - Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2
      agonists on lung function, airway responsiveness, and symptoms in children with
      asthma. The Dutch Chronic Non-specific Lung Disease Study Group.
AB  - In a randomized double-blind multicenter clinical study, 116 children with asthma
      were randomly assigned to treatment with an inhaled beta-2-agonist (salbutamol
      0.2 mg) plus an inhaled corticosteroid (budesonide 0.2 mg) three times a day
      (BA+CS) or to an inhaled beta-2-agonist (salbutamol 0.2 mg) plus a placebo three
      times a day (BA+PL). After a median follow-up time of 22 months, 26 patients
      receiving BA+PL (45%) had withdrawn from randomized treatment, mainly because of
      asthma symptoms, compared with three withdrawals in the patients receiving BA+CS
      (p less than 0.0001). The FEV1, expressed as a percentage of the predicted value
      for age, sex, and height, showed an absolute increase of 7.0% after 2 months of
      BA+CS compared with a decrease of 4.0% after 2 months of BA+PL. This 11%
      difference in percent predicted FEV1 (95% confidence interval, 7 to 15%; p less
      than 0.0001) was then maintained after a median follow-up period of 22 months.
      Postbronchodilator FEV1 showed an absolute increase of 3.7% predicted within 2
      months in patients receiving BA+CS and an absolute decrease of 1.1% predicted in
      children receiving BA+PL (p = 0.0005). Thereafter, this difference between the
      two treatment groups was maintained. Average peak expiratory flow rate (PEFR)
      increased from baseline by 36.6 L/min in the BA+CS group compared with 3.7 L/min
      in the BA+PL group (p = 0.003). This difference then remained for the median
      follow-up time of 22 months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355641
TI  - Canine in vivo tracheal chemotaxis of eosinophils to antigen in sensitized dogs:
      inhibition by a steroid, a systemic lazaroid U-78517F, and several topical H1
      antihistamines.
AB  - Inflammation of the airways contributes to the multicomponent disease known as
      asthma. The primary cells that infiltrate the airway in response to antigen
      exposure are neutrophils and eosinophils. Eosinophils have been implicated in
      much of the histopathology of the airway following infiltration and
      degranulation. We used topical antigen exposure in the trachea of sensitized
      beagle dogs to study the kinetics of eosinophil infiltration with a modified
      double balloon endotracheal tube technique. After establishment of the
      eosinophilia, we used inhibitors with known actions to implicate certain
      mediators in the cellular response. Beagle dogs were sensitized to ascaria ova by
      feeding them orally by gavage. After 6 wk, challenge with 2.0 micrograms/ml
      ascaris antigen protein via the tracheal chamber resulted in a rapid (maximal in
      4 h) and repeatable influx (p less than 0.05 versus vehicle) of eosinophils that
      was faster and larger than that of exogenously added LTB4 or PAF exposure. After
      4 to 6 separate (every 2 wk) antigen challenges in which the response varied by
      (SEM +/- 13 to 50%), the individual dogs were rechallenged in the presence of
      various inhibitors administered either topically in the perfusate or
      systemically. The inhibitors that were effective in blocking the eosinophil
      influx by a statistically significant amount were: (1) the lazaroid U-78517F
      orally 0.5 to 30 mg/kg-18 h (2) Medrol acetate 5 mg/kg intramuscularly-18 h, (3)
      H1-antihistamines topically (10(-6) M) Astemizole, Cetirizine, and Mepyramine,
      also orally 30 mg/kg, and Azelastine. Inhibitors falling to inhibit influx
      topically were a LTB4 receptor antagonist (U-75302) and U-80271 (Merck L-652731),
      a PAF antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355642
TI  - [Chronic myelogenous leukemia with blastic crisis in which expression of P
      glycoprotein was associated with resistance to chemotherapy].
AB  - A 55-year-old woman with chronic myelogenous leukemia developed a lymphoid blast
      crisis (BC) 10 months after diagnosis. By using immunoblotting with a monoclonal
      antibody against P-glycoprotein (P-gp) C219, her leukemia cells from the first
      and 3rd crises were shown to be negative for the P-gp, while the cells of the 4th
      crisis were detected to have a high level of P-gp. This patient did not respond
      to chemotherapy with several anti-cancer agents in the 4th crisis, although
      complete remission was achieved in the first, second and third crises after
      administration of agents including vincristine and prednisolone. Therefore the
      expression of P-gp in the 4th BC might have been closely related to the
      resistance to chemotherapy.

PMID- 1355643
TI  - Cryptorchidism: a prospective study of 7500 consecutive male births, 1984-8. John
      Radcliffe Hospital Cryptorchidism Study Group.
AB  - A total of 7441 boys were examined for cryptorchidism at birth and, if present,
      again at 3 months of age. After excluding boys with severe congenital
      malformations noted at birth, the cryptorchidism rates at 3 months in babies
      weighing less than 2000 g, 2000-2499 g, and greater than or equal to 2500 g were
      7.7%, 2.5%, and 1.41% respectively. The overall rate was 1.55%. The
      cryptorchidism rate at birth had increased by 35.1% and at 3 months by 92.7%,
      over Scorer's rates in the 1950s. Part of these increases may be attributable to
      differences in neonatal mortality, but the increases in babies weighing 2500 g or
      more of 50.2% at birth and 77.4% at 3 months are unlikely to be overestimates. At
      birth 1.92% of boys had bilateral cryptorchidism and 3.0% unilateral
      cryptorchidism. Boys with cryptorchidism at 3 months were more likely to have
      hypospadias, a small scrotum, and poor scrotal rugation compared with boys having
      normally descended testes at birth. Factors predicting descent by 3 months in
      babies cryptorchid at birth are birth weight, laterality and scrotal size, babies
      with low birth weight, bilateral cryptorchidism, and normal scrotal size being
      more likely to have normally descended testes by 3 months. Descent by 3 months
      was more likely the lower the testis along the normal pathway of descent. The
      orchidopexy rate at an average age of 3 years was 1.24%. This is substantially
      lower than in other series and lower than our estimated rate of 2.9% using
      Hospital In-Patient Enquiry data for England and Wales.

PMID- 1355644
TI  - Use of sedatives and muscle relaxants in newborn babies receiving mechanical
      ventilation.

PMID- 1355646
TI  - [Variety of pharmacological action of beta agonists].

PMID- 1355645
TI  - Prevention of exercise induced asthma by inhaled salmeterol xinafoate.
AB  - The effect of inhaled salmeterol xinafoate, a long acting beta 2 agonist, on
      exercise induced asthma was studied in a double blind, crossover, and placebo
      controlled trial. Thirteen asthmatic children with a fall of at least 15% in
      their forced expiratory volume in one second (FEV1) after a standard exercise
      test on a motorised treadmill, on separate days performed the same test 1, 5, and
      9 hours after a single dose of 50 micrograms salmeterol or placebo. FEV1 was
      measured before treatment, and before and for 30 minutes after each exercise
      test. After placebo the number of children with exercise induced asthma was: 10
      at 1 hour, 11 at 5 hours, and 12 at 9 hours. Salmeterol prevented exercise
      induced asthma in all 13 children studied, at 1, 5, and 9 hours. Mean maximum
      falls in FEV1 after exercise were at 1 hour: salmeterol 2.7% and placebo 24.6%, 5
      hours: salmeterol 5.3% and placebo 22.7%; and 9 hours: salmeterol 3.4% and
      placebo 26.6%. After salmeterol the mean increase in FEV1 was 17.8% at 1 hour,
      19.6% at 5 hours, and 19.2% at 9 hours. Inhaled salmeterol prevents exercise
      induced asthma and produces significant bronchodilatation for at least 9 hours.

PMID- 1355647
TI  - Blood phobics and nonphobics: psychological differences and affect during
      exposure.
AB  - This study compared psychological dimensions of blood phobics and nonphobic
      controls, examined affect in response to phobic and neutral stimuli, and
      investigated the relationship between reported feelings of faintness and blood
      pressure. Blood phobics (24 adults with extreme Mutilation Questionnaire scores)
      and 24 nonphobics completed several psychological measures and viewed one of two
      60 sec surgery scenes and a 60 sec neutral scene in counterbalanced order.
      Subjective, psychophysiologic, and motoric measures of affect were assessed. On
      questionnaires, phobics reported greater anxiety sensitivity, empathic distress,
      fear and insecurity, and nightmares, but no difference in autonomic arousal,
      muscle tension, motion sickness, or other empathy domains. During surgery scenes,
      phobics had more negative affect than controls; however, phobics were more
      anxious during only one of the two surgeries, and often only when the surgery was
      presented prior to the neutral scene. Fainting did not occur, and self-reported
      feelings of faintness were unrelated to blood pressure changes. The findings
      highlight the lack of information on blood phobic stimulus properties, fainting's
      relationship to self-reports and blood pressure, and the specific emotion
      experienced in blood phobia.

PMID- 1355648
TI  - Effect of dynorphin A(1-13) on cardiomyocytes in culture: modulation of the
      response to increased extracellular calcium, but no effect on intrinsic cardiac
      contractile frequency or the response to isoproterenol or increased extracellular
      potassium.
AB  - The purpose of this study was to determine whether the endogenous opioid peptide
      dynorphin A(1-13) has a direct effect on the heart or acts to modulate the
      cardiac chronotropic response to calcium, potassium, or beta-adrenergic receptor
      stimulation. Spontaneously contracting myocardial cell aggregates were prepared
      from 7-day-old chick embryos and were maintained in culture for 72 h before
      study. Dynorphin A(1-13), 10(-8) to 10(-6)M, did not alter spontaneous
      contractile frequency. Increases in [Ca2+]o spontaneously suppressed cardiac
      contractile frequency, and dynorphin A(1-13) significantly (p less than 0.05)
      enhanced this response. Nifedipine, 10(-8) M, antagonized the effect of increased
      [Ca2+]o on cardiac contractile frequency, but did not block the action of
      dynorphin A(1-13) to accentuate the effect of increasing [Ca2+]o. Dynorphin A(1
      13) did not alter the significant (p less than 0.05) increase in contractile
      frequency produced by beta-adrenergic receptor stimulation by isoproterenol, or
      the suppression in contractile frequency produced by increases in extracellular
      potassium ([K+]o). These data indicate that dynorphin A(1-13) does not act
      directly on the cardiac myocyte to alter cardiac contractile frequency or alter
      the response to increases in [K+]o or to isoproterenol, but that dynorphin A(1
      13) does modulate the response to increases in extracellular calcium.

PMID- 1355649
TI  - Restriction fragment analysis of the secalin loci of rye.
AB  - Analyses of wheat/rye addition lines by Southern blotting confirmed the presence
      of sequences related to the Sec 1, Sec 2, and Sec 3 loci on chromosomes 1R and
      2R. Comparison of the 1R and 2R addition lines allowed the identification of
      gamma-secalin genes at Sec 1 and Sec 2, respectively, while omega-secalin and
      gamma-secalin genes at Sec 1 were discriminated by comparative hybridization with
      three probes: omega-secalin, total gamma-secalin, and 3' gamma-secalin. The high
      molecular weight (HMW) secalin genes at Sec 3 were identified using a homologous
      HMW subunit probe from wheat. Gene copy numbers were estimated as about 40-60 for
      omega-scalins, 5-10 for gamma-secalins, and 2 for HMW secalins. Comparison of
      individual plants of cv. Gazelle showed a high degree of polymorphism,
      particularly for sequences related to omega-secalins and HMW secalins.

PMID- 1355651
TI  - Cell cycle-dependent changes in tissue transglutaminase mRNA levels in bovine
      endothelial cells.
AB  - The pattern of transglutaminase gene expression through the cell cycle was
      examined by Northern blot analysis using cultured bovine endothelial cells and a
      cDNA probe. When the cells reached confluency or were arrested in G0/G1 phase by
      nutrition deprivation, transglutaminase mRNA rose to a very high level; S- and M
      phase extracts showed high and low levels, respectively. Subcellular localization
      studies by sucrose gradient centrifugation and immunostaining demonstrated that
      the majority of transglutaminase is present in cytosols throughout the cycle. The
      cell cycle-dependent changes in the transglutaminase mRNA levels strongly support
      the implicated involvement of the enzyme in cell growth, differentiation, and
      senescence.

PMID- 1355650
TI  - Rationally designed selective inhibitors of trypanothione reductase.
      Phenothiazines and related tricyclics as lead structures.
AB  - Trypanothione reductase, an essential component of the anti-oxidant defences of
      parasitic trypanosomes and Leishmania, differs markedly from the equivalent host
      enzyme, glutathione reductase, in the binding site for the disulphide substrate.
      Molecular modelling of this region suggested that certain tricyclic compounds
      might bind selectively to trypanothione reductase without inhibiting host
      glutathione reductase. This was confirmed by testing 30 phenothiazine and
      tricyclic antidepressants, of which clomipramine was found to be the most potent,
      with a K(i) of 6 microM, competitive with respect to trypanothione. Many of these
      compounds have been noted previously to have anti-trypanosomal and anti
      leishmanial activity and thus they can serve as lead structures for rational drug
      design.

PMID- 1355652
TI  - The N-terminal hexapeptide fragment of IGF II stimulates thymidine incorporation
      into fibroblasts.
AB  - We synthesized the N-terminal hexapeptide fragment of IGF II to study potential
      binding to NMDA receptors in analogy to the N-terminal tripeptide of IGF I. The
      amino acid sequence of the hexapeptide is furthermore identical with the C
      terminal sequence of the casiragua insulin B chain. The hexapeptide did not bind
      to the NMDA receptors, but was found to promote [3H]-thymidine incorporation into
      fibroblasts at concentrations of 10(-8) - 10(-5) M in a dose-dependent manner.
      Since [125I]-hexapeptide did not bind to IGF receptors, indirect competition
      studies using either labelled IGFs or insulin had to be used. The competition of
      hexapeptide at a concentration of 10(-5) M with labelled IGF I or II was about
      equal to that of 10(-9) M IGF I or II. IGF receptors were apparently up-regulated
      by the hexapeptide, as has also been described for insulin. When using casiragua
      insulin as labelled ligand, IGF II and casiragua insulin competed with equal
      potency, whereas the hexapeptide at 10(-7) M caused an apparent up-regulation of
      the casiragua insulin binding sites. Our results that the hexapeptide stimulates
      [3H]-thymidine incorporation and up-regulates IGF II and casiragua insulin
      binding sites may be connected to one or several of the following findings: the
      hystricomorph insulins--of which the casiragua insulin is a member--stimulate DNA
      synthesis to a greater extent than other insulins; the insulin and type 1 IGF
      receptor binding regions are localized predominantly in the C-terminal region of
      the insulin B chain; and the "cooperative" site regulating the affinity of the
      insulin receptor is also located in the C-terminal region of the insulin B chain.
      Further experiments will be needed to clarify the exact mechanism.

PMID- 1355653
TI  - Dopamine fiber growth induction by implantation of synthetic dopamine-containing
      microspheres in rats with experimental hemi-parkinsonism.
AB  - Injectable local drug delivery formulations-so-called microspheres have recently
      been developed, in which drugs are microencapsulated within biocompatible and
      biodegradable copolymer excipients like poly[DL-lactide-co-glycolide]. In view of
      its potential therapeutical usefulness, we have studied the microsphere
      methodology as a means to substitute for experimentally induced subnormal levels
      of endogenous dopamine (DA). Administration of 6-hydroxydopamine (6-OH-DA)
      unilaterally in the medial forebrain bundle of rats results in an up-regulation
      of postsynaptic receptors in the denervated striatum, functionally manifested as
      contralateral rotational behavior after apomorphine. DA microspheres were
      implanted in the denervated striatum. The majority of the rats displayed an
      attenuation of the contralateral rotational behavior induced by apomorphine up to
      8 wk postimplantation. Immunocytochemical observations unexpectedly demonstrated
      growth of DA and tyrosine hydroxylase immunoreactive fibers in the denervated
      striatum. Interestingly, there was an apparent correlation between functional
      recovery and the degree of growth of DA fibers. The present results suggest that
      implantation of DA microspheres may promote DA fiber growth and extended recovery
      of surviving DA neurons, and, therefore, could be of therapeutic usefulness in
      Parkinson's disease.

PMID- 1355655
TI  - Evidence by in situ hybridization that c-erbB-2 proto-oncogene expression is a
      marker of malignancy and is expressed in lung adenocarcinomas.
AB  - In order to identify potential markers of malignancy in diagnostic respiratory
      cytopathology, c-myc and c-erbB-2 proto-oncogene expression was studied in fine
      needle aspirates from 14 consecutive fresh operation tissue samples (after
      surgical removal) representing lung tumors and a variety of other cell samples by
      in situ hybridization of 35S-labeled antisense and sense RNA c-myc and c-erbB-2
      specific proto-oncogene probes. All 14 lung tumors showed c-myc expression and
      eight also showed c-erbB-2 expression. On average, the c-myc expression was about
      4 times higher than that of c-erbB-2 (P less than 0.001). c-erbB-2 expression,
      confirmed also as a cytoplasmic membrane-bound reactivity by immunohistochemical
      stainings for c-erbB-2 oncoprotein, was significantly related to adenocarcinoma
      (P less than 0.025), whereas increasing tumor size correlated significantly with
      increasing c-myc expression (P less than 0.05). On average, all the tumor cell
      lines showed 2-fold expression of c-myc compared with the lung tumors (P less
      than 0.025). c-erbB-2 expression was found in six of 11 cell lines. High c-myc
      proto-oncogene expression was also found in broncho-epithelial cells and alveolar
      macrophages, and a low expression was found in lymphocytes but not in
      neutrophils, while none of these cells showed c-erbB-2 proto-oncogene expression.
      Our results demonstrate extensive c-myc proto-oncogene expression in both
      malignant and non-neoplastic proliferating cells, but not in terminally
      differentiated cells such as neutrophils. Therefore c-myc expression must also be
      related to general cell proliferation and not only malignancy per se. In marked
      contrast, c-erbB-2 proto-oncogene expression was found only in adenocarcinoma
      cells, and thus can be used as a marker for malignancy in diagnostic respiratory
      cytopathology.

PMID- 1355654
TI  - Comparative accuracy of fixed partial dentures made as one-piece castings or
      joined by solder.
AB  - Four-unit fixed partial dentures were fabricated as a one-piece casting or as two
      piece castings joined by soldering prior to the addition of porcelain. The
      accuracy of the two techniques was compared and evaluated using an anatomic cast
      metal master model. All procedures, including SEM measurements, were performed
      directly on the master model. The cast one-piece units had smaller vertical
      marginal openings than did the soldered units. The rigid nature of the abutments
      evokes the problems occurring with osseointegrated implants.

PMID- 1355656
TI  - Carbohydrate antigens of embryonal carcinoma cells: changes upon differentiation.
AB  - Embryonal carcinoma (EC) cells, the malignant stem cells of teratocarcinomas,
      resemble early embryonic cells morphologically, developmentally, and with respect
      to several cell surface characteristics. EC cells often differentiate into a
      variety of cell types when treated with chemical agents such as retinoic acid, or
      when placed in a normal embryonic environment. Developmentally regulated surface
      antigens of EC cells and their differentiated derivatives have been defined using
      monoclonal antibodies. Many of these "differentiation antigens" have proved to be
      oligosaccharide chains carried on membrane glycolipids and/or glycoproteins. Our
      analyses of glycolipid composition in a pluripotent human EC cell line, NTERA-2,
      have revealed a complex set of glycoslylation changes that occur during cellular
      differentiation. Like early embryos, undifferentiated NTERA-2 EC cells express
      predominantly globo-series glycolipids. However, once differentiation is
      initiated by addition of retinoic acid there is a marked shift of cellular
      glycolipids from globo-series to lacto- and ganglio-series. Distinct subsets of
      differentiated cells are characterized by their expression of different patterns
      of glycolipid antigens. These changes in cell surface phenotype may serve to mark
      cellular identity and facilitate morphogenetic cell interactions during embryonic
      development.

PMID- 1355657
TI  - Microbial interaction with animal cell surface carbohydrates.
AB  - Microbes have selected primarily carbohydrates for attachment to host animal
      cells. Recent studies have revealed essential characteristics in the recognition
      of receptor carbohydrates. Of importance is the property of recognizing also
      sequences placed inside an oligosaccharide chain, which differs from most animal
      antibodies. This is the basis for series of isoreceptors with the minimum
      receptor sequence in common but with separate neighbouring groups. There are
      families of microbial ligands that show different preferences for members within
      one series of isoreceptors, indicating only slight differences in the
      complementary binding sites of the proteins. Such differences may explain shifts
      in the selectivity of separate host tissues for infection. A second
      characteristic is the low affinity interaction often found where simple receptor
      containing saccharides are unable to inhibit attachment. Technical possibilities
      are rapidly developing for the design of synthetic receptor analogues to be used
      in the therapy of clinical infections. This is urgently needed in cases where no
      rational therapy exists today.

PMID- 1355658
TI  - Prevention of HIV-2 and SIV infections in cynomolgus macaques by prophylactic
      treatment with 3'-fluorothymidine.
AB  - The aim of this study was to determine the usefulness of human immunodeficiency
      virus type 2 (HIV-2) for in vivo evaluation of antiviral drugs in monkeys and to
      study if prophylactic treatment with 3'-fluorothymidine (FLT) could prevent
      infection against a low challenge dose of HIV-2 or simian immunodeficiency virus
      (SIV). Protection against infection was assessed by virus isolation and
      polymerase chain reaction (PCR) on monkey peripheral blood mononuclear cells
      (PBMC) as well as by antibody and viral antigen assays. Prophylactic treatment
      with FLT 3 x 5 mg/kg/day, starting 8 h prior to virus inoculation, prevented HIV
      2 infection in 3 of 8 monkeys. In another experiment 2 of 4 monkeys resisted 2-10
      monkey infectious doses (MID50) of SIV with the same prophylactic treatment. All
      control animals (HIV-2 n = 8, SIV n = 4) became infected. Thus, FLT treatment
      prevented HIV-2 and SIV infection in 5 of 12 animals.

PMID- 1355659
TI  - Human pancreatic cancer cell lines do not express receptors for somatostatin.
AB  - The in vivo administration of somatostatin (SS) or its analogues is capable of
      suppressing the growth of pancreatic cancer in experimental animals. We examined
      the effects of SS-14 and its analogue RC-160 on the in vitro growth of two human
      pancreatic cancer cell lines MiaPaCa-2 and Panc-1 stimulated with epidermal
      growth factor (EGF) or insulin-like growth factor 1 (IGF-1). Neither SS-14 nor RC
      160 inhibited the growth of either cell line. In contrast RC-160 did inhibit the
      EGF-stimulated growth of a rat pancreatic cancer cell line AR42J. Binding studies
      with 125I-Tyr11 somatostatin revealed the presence of a single class of high
      affinity binding sites with a Kd of 0.20 +/- 0.05 nM and a Bmax of 2.1 +/- 0.26
      pmoles mg-1 protein on AR42J but not displaceable binding was observed on MiaPaCa
      2 or Panc-1. We conclude that lack of receptors accounts for the failure of SS-14
      and RC-160 to influence the growth of human pancreatic cancer in vitro. These
      results, taken together with other findings, lead us to question the therapeutic
      efficacy of somatostatin and its analogues as mono-therapy in the treatment of
      human pancreatic cancer.

PMID- 1355661
TI  - P-glycoprotein expression in locally advanced breast cancer treated by
      neoadjuvant chemotherapy.
AB  - Using immunohistochemistry and the monoclonal antibody C219 we have investigated
      P-glycoprotein expression in 26 locally advanced breast cancers. Twenty four
      patients had received four cycles of chemotherapy (mitozantrone, mitomycin-C and
      methotrexate) prior to mastectomy; two received tamoxifen. Twelve tumours
      exhibited an objective response to the chemotherapy. A background pattern of
      isolated weakly positive (1+) stromal staining (myofibroblast) was observed in
      seven tumours, two of which had been treated by tamoxifen alone. Two of the
      tumours treated by induction chemotherapy showed positive staining (1+) within a
      very small number of isolated tumour cells (maximum of three) and macrophages.
      The significance of this staining is not clear although C219 may simply be cross
      reacting with myosin. We have failed to demonstrate a clear clinical utility for
      C219 in breast cancer, particularly regarding the identification of patients in
      whom MDR chemotherapy be avoided once metastases develop.

PMID- 1355660
TI  - Mdr1/P-glycoprotein, topoisomerase, and glutathione-S-transferase pi gene
      expression in primary and relapsed state adult and childhood leukaemias.
AB  - In a variety of adult and childhood leukaemia cell samples collected at different
      states of the disease, we analysed in a series of sequentially performed slot
      blot or Northern-blot hybridisation experiments the expression of genes possibly
      involved in multiple drug resistance (MDR) (mdr1/P-glycoprotein, DNA
      topoisomerase II, glutathione-S-transferase pi), and the expression of the DNA
      topoisomerase I and histone 3.1 genes. Occasionally, P-glycoprotein gene
      expression was additionally examined by indirect immunocytofluorescence using the
      monoclonal antibody C219. No significant difference in mdr1/P-glycoprotein mRNA
      levels between primary and relapsed state acute lymphocytic leukaemias (ALL) was
      seen on average. Second or third relapses, however, showed a distinct tendency to
      an elevated expression of this multidrug transporter gene (up to 10-fold) in part
      well beyond the value seen in the moderately cross-resistant T-lymphoblastoid
      CCRF-CEM subline CCRF VCR 100. Increased mdr1/P-glycoprotein mRNA levels were
      also found in relapsed state acute myelogenous leukaemias (AML), and in chronic
      lymphocytic leukaemias (CLL) treated with chlorambucil and/or prednisone for
      several years. Topoisomerase I and topoisomerase II mRNA levels were found to be
      very variable. Whereas in all but one case of CLL topoisomerase II mRNA was not
      detected by slot-blot hybridizations, strong topoisomerase I and topoisomerase II
      gene expression levels, frequently exceeding the levels monitored in the CCRF-CEM
      cell line, were seen in many cell samples of acute leukaemia. If topoisomerase II
      mRNA was undetectable, expression of topoisomerase I was clearly visible
      throughout. These observations might be valuable considering the possible
      treatment with specific topoisomerase I or topoisomerase II inhibitors.
      Significant positive correlations were found (i) for topoisomerase I and histone
      3.1 gene expression levels in general (P less than 0.001), and (ii) in the CLL
      samples additionally for the expression levels of the mdr1 gene, and the histone
      3.1, topoisomerase I, and glutathione-S-transferase pi genes, respectively.

PMID- 1355662
TI  - p53 protein expression in human breast carcinoma: relationship to expression of
      epidermal growth factor receptor, c-erbB-2 protein overexpression, and oestrogen
      receptor.
AB  - The expression of p53 protein, oestrogen receptor protein, epidermal growth
      factor receptor (EGFR) and overexpression of the c-erbB-2 oncoprotein was
      examined in a series of 149 primary symptomatic breast carcinomas. Expression of
      p53 was present in 62 of 146 cases (42.5%) of the invasive carcinoma and one of
      three cases (33.3%) of ductal carcinoma in situ (DCIS) examined. Statistical
      associations of tumour oestrogen receptor positivity and lack of p53 protein
      expression, chi 2 = 19.78 (d.f. = 1), P less than 0.001, positive tumour p53
      status and poor tumour grade; chi 2 = 14.1 (d.f. = 2), P less than 0.001, EGFR
      expression chi 2 = 7.07, (d.f. = 1), P less than 0.01 and tumour c-erbB-2 protein
      overexpression; chi 2 = 4.61 (d.f. = 1), P = 0.032 were identified. Expression of
      p53 is rare in invasive lobular carcinoma of classical type (8.3% of cases
      examined) in contrast to other common types of mammary carcinoma. Non-significant
      trends of p53 protein expression and increased regional tumour recurrence; chi 2
      = 3.20 (d.f. = 1), P = 0.074 and also poorer patient survival; chi 2 = 3.76 (d.f.
      = 1), P = 0.053 were identified. p53 protein expression is a common event in
      human breast cancer and is present in both DCIS and invasive mammary carcinoma.
      Abnormal expression of p53 protein is a feature of both in situ and invasive
      breast carcinoma, implying that the abnormal p53 protein expression may be
      implicated in the early stages of mammary carcinoma progression.

PMID- 1355663
TI  - Glutathione S-transferase expression in the human testis and testicular germ cell
      neoplasia.
AB  - Glutathione S-transferase (GST) isoenzyme expression is altered in a variety of
      neoplasms and the enzymes are implicated in metabolism of carcinogens and
      resistance to drugs, including cisplatin. We have studied GST Alpha, Pi, Mu and
      microsomal isoenzyme expression by immunohistochemistry in normal and cryptorchid
      testes, intratubal germ cell neoplasia (ITGCN), seminoma and non-seminomatous
      germ cell tumours. In 16 stage II-IV malignant teratoma intermediate (MTI) both
      orchidectomy and post-treatment residual surgical masses were studied. All four
      isoenzymes were strongly expressed in Leydig and Sertoli cells. GST Pi was absent
      from normal spermatogonia but strongly expressed by the neoplastic germ cells of
      ITGCN and seminoma. GST Pi was strongly expressed in all elements of teratoma,
      irrespective of differentiation. There were no qualitative differences in
      expression between primary and post-chemotherapy metastases. GST Alpha expression
      in teratoma correlated with epithelial differentiation. GSTs may be important in
      normal spermatogenesis and protection of germ cells from teratogens and
      carcinogens. They may have a role in testicular tumour drug resistance but this
      role is not well defined. GST Pi is a new marker for ITGCN.

PMID- 1355665
TI  - Effects of intravenous fenoldopam (SK&F 82526-J) on blood pressure in severe
      hypertension. SK&F Fenoldopam Working Group.

PMID- 1355664
TI  - Comparison of ketanserin and celiprolol on regression of left ventricular
      hypertrophy in older hypertensive patients.
AB  - The effects of ketanserin, a specific serotonin2-receptor agonist, and
      celiprolol, a new, highly cardioselective beta 1 blocker with partial beta 2
      agonist activity and peripheral vasodilating properties, on left ventricular (LV)
      structure and function were assessed in 60 older hypertensive patients (greater
      than 55 years) with clinical LV hypertrophy (LV mass index greater than 130
      g/m2). The patients were studied using echocardiography after 1 month of placebo
      treatment, and 6 and 18 months of monotherapy with active drug. Ketanserin and
      celiprolol lowered blood pressure to normal levels. Heart rate did not change
      with ketanserin and fell moderately (-5%) with celiprolol (p less than .001).
      Regression of LV hypertrophy was achieved with the use of either medication (p
      less than .0001), although the magnitude of reduction in LV mass was greater with
      celiprolol at both 6 months (-10% vs -5%, p = .001) and 18 months (-13% vs -7%, p
      = .002). While LV volume did not change with either drug, celiprolol tended to
      decrease it, resulting in a 5% reduction in cardiac index (p = .01), which was
      associated with mild bradycardia. Ketanserin did not change LV ejection fraction,
      whereas celiprolol caused a slight (1.5%) long-term improvement (p = .003).
      Systolic wall stress and total peripheral resistance decreased with both agents
      (p less than .01), with no between-group differences. In conclusion, anti
      hypertensive treatment of older persons with ketanserin or celiprolol achieves
      regression of LV hypertrophy without associated deleterious effects on LV
      function.

PMID- 1355666
TI  - ATPase activity of partially purified P-glycoprotein from multidrug-resistant
      Chinese hamster ovary cells.
AB  - In vitro studies of multidrug-resistant cell lines have shown that a membrane
      protein, the P-glycoprotein, is responsible for resistance to a wide range of
      structurally and functionally dissimilar anti-cancer drugs. The amino-acid
      sequence of P-glycoprotein (Pgp) indicates two consensus sequences for ATP
      binding and the purified protein has been reported to possess a low level of
      ATPase activity. As part of our goal to further characterize the ATPase activity
      of P-glycoprotein, we have developed a procedure for rapid partial purification
      of the protein in a highly active form. Plasma membrane vesicles from multidrug
      resistant CHRC5 Chinese hamster ovary cells were subjected to a two-step
      procedure involving selective extraction with different concentrations of the
      zwitterionic detergent CHAPS. The resulting extract was enriched in P
      glycoprotein (around 30% pure) and displayed an ATPase activity (specific
      activity 543 nmol mg-1 min-1) that was not found in a similar preparation from
      drug-sensitive cells. The ATPase specific activity was over 10-fold higher than
      that previously reported for immunoprecipitated Pgp and 280-fold higher than that
      of immunoaffinity-purified Pgp. This ATPase activity could be distinguished from
      that of other ion-motive ATPases and membrane-associated phosphatases and is,
      thus, proposed to be directly attributable to P-glycoprotein. Optimal P
      glycoprotein ATPase activity required Mg2+ at an ATP: Mg2+ molar ratio of 0.75:1
      and the apparent Km for ATP was 0.88 mM. P-Glycoprotein ATPase could be
      completely inhibited by vanadate and by the sulfhydryl-modifying reagents N
      ethylmaleimide, HgCl2 and p-chloromercuribenzenesulfonate. Certain drugs and
      chemosensitizers, including colchicine, progesterone, nifedipine, verapamil and
      trifluoperazine, produced up to 50% activation of P-glycoprotein ATPase activity.

PMID- 1355667
TI  - Transport properties of P-glycoprotein in plasma membrane vesicles from multidrug
      resistant Chinese hamster ovary cells.
AB  - Multidrug resistant (MDR) cells overexpress a 170-180 kDa membrane glycoprotein,
      the P-glycoprotein, which is believed to export drugs in an ATP-dependent manner.
      Plasma membrane vesicles from the MDR CHRC5 cell line, but not the AuxB1 drug
      sensitive parent, showed uptake of [3H]colchicine and [3H]vinblastine that was
      stimulated by the presence of ATP and an ATP-regenerating system. Steady-state
      uptake of drugs was achieved by 10 min and was stable for greater than 30 min.
      Non-hydrolysable ATP analogues were unable to support drug uptake, indicating
      that ATP hydrolysis is essential for transport. ATP-stimulated drug uptake
      appeared to result from drug transport into inside-out vesicles, since uptake was
      osmotically sensitive and could be prevented by detergent permeabilization.
      Steady-state uptake was half-maximal at 100 microM colchicine and 200 nM
      vinblastine and was inhibited by a 10-100-fold excess of MDR drugs and
      chemosensitizers, in the order vinblastine greater than verapamil greater than
      daunomycin greater than colchicine. In addition to being vanadate-sensitive, drug
      uptake was inhibited by 10-200 microM concentrations of several sulfhydryl
      modifying reagents, suggesting that cysteine residues play an important role in
      drug transport. Vesicular colchicine was rapidly exchanged by an excess of
      unlabelled drug, demonstrating that drug association is the net result of
      opposing colchicine fluxes across the membrane.

PMID- 1355669
TI  - [XXth Congress of the Spanish Society of Internal Medicine. Barcelona, 16-19
      September 1992. Abstracts].

PMID- 1355668
TI  - Cell-surface changes induced by ectopic expression of the murine homeobox gene
      Hox-3.3.
AB  - Murine homeobox-containing genes (Hox genes) are postulated as playing key roles
      in the establishment of the anterior-posterior embryonic body axis, possibly
      providing cells with positional cues. Little is known, however, concerning how
      cells might respond to homeobox gene expression to interpret these cues. Since
      changes in the cell-surface are central to many processes in early development we
      reasoned that cells expressing different complements of Hox genes might have
      different surface properties. In order to investigate this we have used the
      sensitive, non-disruptive technique of multiple two-phase aqueous partition,
      which is able to detect small differences on the surface of intact cells. Using
      this technique we have found that ectopic expression of the murine Hox-3.3 gene
      in cultured cells induces reproducible changes in the cell surface. Changes only
      occurred above a threshold level of gene expression, but above this level a
      correlation between surface change and gene expression was seen. The implications
      for the establishment of a 'Hox' code of homeobox genes acting to specifically
      change cell-surface properties are discussed.

PMID- 1355670
TI  - Neurotransmitter antagonists block some odor responses in olfactory receptor
      neurons.
AB  - The first step in olfactory transduction is the recognition of odor molecules by
      membrane bound receptors belonging to the superfamily of G-protein coupled
      receptors; other members of this family are involved in neurotransmission. Based
      on the considerable homology between individual members of this family, we have
      investigated the ability of well-known neurotransmitter antagonists to block the
      olfactory response. Adrenergic and muscarinic antagonists were found to block
      some odor induced currents (45-55%) with an IC50 between 15 and 75 microM. By
      contrast, antagonists of glutamate and GABA receptors, which do not belong to
      this receptor superfamily, were ineffective. These results suggest that further
      pharmacological analysis may be useful for characterizing and classifying the
      family of odor receptors.

PMID- 1355671
TI  - Kainate/glutamate-induced changes in intracellular calcium and pH in leech glial
      cells.
AB  - Kainate evokes a non-desensitizing membrane depolarization in neuropile glial
      cells of the leech Hirudo medicinalis. We measured membrane potential and
      intracellular pH, pH(i), using double-barrelled pH-sensitive microelectrodes, and
      intracellular calcium, Ca2+i, using the change in fluorescence ratio of
      intracellularly injected fura-2, in these glial cells in situ. 20-50 microM
      kainate produced a depolarization of 18-28 mV and a decrease of pH(i) by 0.27 +/-
      0.07 pH units. Ca2+i increased by 306 +/- 128 nM upon kainate, which could be
      inhibited by the non-NMDA antagonist CNQX. Glutamate (0.1 mM) also produced a
      fall in pH(i) and a rise in Ca2+i, which were however, much smaller. Quisqualate
      and N-methyl-D-aspartate had only small or no effects on membrane potential,
      pH(i) or Ca2+i. It is concluded that leech neuropile glial cells have a kainate
      type glutamate receptor, which mediate significant transients of intracellular H+
      and Ca2+.

PMID- 1355672
TI  - Granulocyte-macrophage colony-stimulating factor induces neutrophil adhesion to
      pulmonary vascular endothelium in vivo: role of beta 2 integrins.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) causes upregulation of
      neutrophil surface CD11b/CD18 expression, and enhances the adhesion of
      neutrophils to cultured human endothelial cells in vitro. Systemic administration
      of GM-CSF results in a rapid, transient decrease in circulating phagocyte
      numbers. Using a nonhuman primate model (Cynomolgus), we provide histologic
      evidence that this transient leukopenia is associated with the margination of
      neutrophils in the pulmonary microcirculation. In four animals receiving 2 to 15
      micrograms/kg recombinant human GM-CSF (rhGM-CSF), light microscopic sections of
      lung contained 36 +/- 8, 17 +/- 7, 21 +/- 6, and 15 +/- 8 (mean +/- SD, n = 20)
      neutrophils within a graticule grid, as compared with two control animals
      receiving saline injections whose lung sections contained 2.1 +/- 1.6 and 3.1 +/-
      2.1 (mean +/- SD, n = 20) neutrophils within the same grid. Scanning electron
      microscopy shows activated leukocytes adherent to pulmonary vascular endothelium,
      but no morphologic evidence of endothelial damage, and no migration of cells into
      the extravascular space. Margination is associated with an increase in surface
      expression of CD11b/CD18 on circulating phagocytes, which could contribute to the
      adhesion to capillary endothelial cells, but CD11b/CD18 levels remain elevated
      even when demargination is complete. In vitro, monoclonal antibodies (MoAbs) to
      CD18 and CD11b were able to inhibit neutrophil aggregation and adhesion to
      endothelium. FMLP-induced neutrophil aggregation was inhibited by 39.8% +/- 11.5%
      and 44.8% +/- 12.3%, respectively, by MoAbs to CD18 and CD11b (P less than .0005,
      n = 4 for both); a similar effect was demonstrated on TPA-induced aggregation.
      MoAb CD18 reduced the adhesion of unstimulated neutrophils to endothelium by 44%
      (P less than .01, n = 7), and inhibited the amount of GM-CSF-stimulated adhesion
      by 74% (P less than .001, n = 7), while MoAb to CD11b produced a reduction of
      unstimulated neutrophil adhesion by 30%, and of GM-CSF-stimulated adhesion by 40%
      (P less than .01, n = 5, for both). However, when administered in vivo, MoAb CD18
      produced only a small, albeit significant, amelioration of GM-CSF-induced
      margination in vivo, while MoAb CD11b was without effect. These results show that
      GM-CSF-induced transient leukopenia is associated with enhanced neutrophil
      adherence to pulmonary vascular endothelium, but suggest that the beta 2
      leukocyte integrins CD11/CD18 play only a minor role in this process.

PMID- 1355673
TI  - 2-Chlorodeoxyadenosine in the treatment of multiple myeloma.

PMID- 1355674
TI  - Trauma involving the dentition and supporting tissues.
AB  - Successful treatment of traumatic injuries depends on timely action by the
      patient and a quick and accurate diagnosis by the dentist. Although most injuries
      are minor and of an urgent nature, displaced or missing teeth are true
      emergencies. The mismanagement of dental traumatic injuries has provided much
      information as well as questions for research that have resulted in the increased
      retention of teeth with as little treatment as possible. Maintaining pulp
      vitality when possible, utilizing the therapeutic effects of calcium hydroxide,
      and returning teeth to function as soon as possible are keys to predictable
      prognosis.

PMID- 1355675
TI  - New developments in synthetic bone replacement materials.
AB  - Synthetic bone replacement materials continue to be much discussed in the current
      periodontal literature. Numerous reports have shown their clinical use in the
      treatment of intraosseous defects. Periodontal treatment aims also include
      regeneration of a new functional attachment. Although histologic studies have
      shown that most of the synthetic bone substitutes can enhance bone formation,
      they are not able to promote new attachment of periodontal tissues to the root
      surface previously exposed. Future studies are needed to assess whether these
      materials could be of use together with growth factors in composite grafts or in
      conjunction with guided tissue regeneration techniques.

PMID- 1355676
TI  - The amphicrine pancreatic cell line AR42J: a model system for combined studies on
      exocrine and endocrine secretion.
AB  - Secretory vesicles of both the exocrine and the endocrine pancreas have been
      isolated and characterized in molecular terms from pancreatic tissue and primary
      cell cultures. Studies on pancreatic secretory processes could be further
      facilitated by the use of permanent cell lines that respond to secretory stimuli
      with a regulated secretory response. We now present biochemical, morphological
      and secretory studies on the rat pancreatic acinar cell line AR42J. This cell
      line is characterized by the presence of digestive enzyme-containing dense core
      vesicles, which are released in response to cholecystokinin. In addition, we
      present evidence that these cells also contain small neuroendocrine-specific
      vesicles, as evidenced by the expression of the neuroendocrine-specific vesicle
      proteins synaptophysin and S.V.2. Corresponding to these mixed exocrine
      neuroendocrine features, we also found considerable amounts of the
      neurotransmitters glycine, glutamine and gamma-aminobutyric acid (GABA), as well
      as the rate-limiting enzyme in GABA synthesis, glutamic acid decarboxylase (GAD)
      (EC 4.1.1.15) expressed in these cells. We demonstrated a specific uptake
      mechanism for radioactively-labelled GABA by these cells. In addition, GABA was
      released from intracellular storage pools by nicotinic receptor stimulation or
      membrane depolarization. In summary, AR42J cells represent the first amphicrine
      pancreatic cell line with the combined expression of exocrine and neuroendocrine
      secretory organelles, both of which follow a regulated secretory pathway in
      response to various secretory stimuli.

PMID- 1355677
TI  - Nicotine-induced airway smooth muscle contraction: neural mechanisms involving
      the airway epithelium. Functional and histologic studies in vitro.
AB  - To assess the mechanism of and the role of the epithelium in nicotine-induced
      bronchoconstriction in vitro, we performed a combined functional and histologic
      study. Functional study: We suspended tracheal strips or rings from 16 ferrets
      (1124 +/- 561 g, mean +/- SD) in organ baths. Alternate tracheal strips had their
      epithelium removed. Dose-response curves to acetylcholine (ACh) and nicotine were
      established for pairs of tissues with and without epithelium, each pair receiving
      only one dose of nicotine. Nicotine induced brief muscle contractions not
      exceeding 25% of the ACh-induced maximum. Contractions were blocked by
      hexamethonium and 10(-7) M atropine and were abolished or inhibited strongly by
      tetrodotoxin (TTX), suggesting the involvement of nicotinic neuronal and
      muscarinic smooth muscle receptors. Removal of the epithelium strongly inhibited
      contractions at concentrations of nicotine greater than 3 x 10(-5) M which
      completely removed any dose-response effect. ACh-induced contractions were
      unchanged, demonstrating smooth muscle integrity. We suggest that the removal of
      the epithelium attenuates nicotine-induced bronchoconstriction through the
      removal of nerves running in or close to the epithelium. Histologic study: In
      tracheae from 15 ferrets (8 male, 7 female), mean weight (+/- SD) 1288 (+/- 470)
      g, we examined 4 techniques of epithelium removal: (1) gentle scraping with a
      scalpel blade moved backwards (away from the cutting edge), (2) moving a Q-tip
      through the unopened tracheal tube without lateral pressure, and (3, 4) stroking
      the mucosa of opened tracheal segments with a Q-tip, exerting (3) light or (4)
      moderate pressure. All methods were equally (97%-100%) efficient in removing the
      epithelium but differed in the amount of damage caused to the basement membrane
      and/or submucosal tissue. Method (2) caused less damage to the basement membrane
      than the other methods but still removed almost one-third of it. The study showed
      that complete removal of the epithelium is at the expense of the submucosa and
      that a given result of "epithelium removal" is also attributable to removal of
      the neighboring subepithelial structures.

PMID- 1355680
TI  - Proceedings of the Symposium on Bone Marrow Transplantation. Keystone, Colorado,
      January 13-26, 1992.

PMID- 1355678
TI  - Mutant genes of cytochrome P-450IID6, glutathione S-transferase class Mu, and
      arylamine N-acetyltransferase in lung cancer patients.
AB  - Epidemiological studies suggested a protective effect of certain phenotypes of
      polymorphic foreign-compound-metabolizing enzymes in some types of cancer. Poor
      metabolizers (PM) of debrisoquine 4-hydroxylase (cytochrome P-450IID6, CYP2D6)
      were found to be underrepresented among patients with lung cancer. Recent
      advances in molecular genetic characterization of CYP2D6, glutathione S
      transferase (GST) class Mu, and arylamine N-acetyltransferase enabled genotypical
      determination of mutant alleles in lung cancer patients. Restriction fragment
      length polymorphism (RFLP) with a cDNA gene probe of CYP2D6 was analyzed in 79
      lung cancer patients who were phenotyped with debrisoquine. Mutant alleles were
      detected by allele-specific polymerase chain reaction (PCR). In the same
      individuals, genotype of GST class Mu was analyzed by PCR and correlated with ex
      vivo activity of glutathione conjugation towards trans-stilbene oxide. RFLP
      patterns allowed discrimination between the slow and fast genotype of N
      acetyltransferase as well as the heterozygotes. Three phenotypical PMs of
      debrisoquine (3.8%) were confirmed by PCR and RFLP. No PM could be unambiguously
      recognized only by RFLP patterns. The PMs were characterized by PCR and RFLP as
      carriers of the 29B/29B (n = 1), 29A/29B (n = 1), and 29A/44 (n = 1) mutant
      alleles. Higher debrisoquine hydroxylase activities were found in the homozygous
      EMs, who possess two active genes, as compared to heterozygous EMs, who have only
      one active gene. The patients with phenotypically impaired GST Mu activity were
      confirmed as such by PCR. A complete correspondence between phenotyping of N
      acetyltransferase (with caffeine) and genotyping was found. The new genetic
      techniques proved to be powerful tools for molecular-epidemiological studies
      aimed at establishing host factors of cancer susceptibility.

PMID- 1355681
TI  - The fetus as an optimal donor and recipient of hemopoietic stem cells.
AB  - In the present work we used allogeneic in utero transplantation of fetal stem
      cells in sheep and monkeys. Thus, both the donor and recipient cells had
      preimmune status. We showed engraftment of allogeneic stem cells in the tolerant
      environment of the host. The engrafted cells showed trilineage (lymphoid,
      erythroid and myeloid) expression of differentiation. Long term maintenance of
      these engrafted cells was observed. We also demonstrated that ex vivo incubation
      of donor cells with growth factor can enhance the engraftment. Moreover, we have
      shown that the engrafted cells respond to phlebotomy in the same manner as
      endogenous cells. We, therefore, conclude that (a) Preimmune fetuses are highly
      suitable for stem cell transplantation both as donors and recipients. (b)
      Engraftment can be modulated by brief maneuvers such as ex vivo manipulation. (c)
      Functionally, the engrafted cells can respond to hemopoietic stimuli in a similar
      manner as the endogenous cells. Implications of this transplantation system in
      clinical medicine is discussed. Everyone who is involved in organ transplantation
      must, sooner or later, come to grips with immunological barriers which
      establishes the individuality of each organism by recognizing "self" from "non
      self". Transplanters must overcome this barrier, if allogeneic organ
      transplantation is to be successful. In the case of hemopoietic stem cells (HSC),
      where immunocompetent cells are transplanted, graft-vs-host disease (GVHD) may
      also be expected. Tolerance can be expected when the recipient is genetically
      immunodeficient, thus being unable to mount an immunological barrier.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1355679
TI  - Differentiation of mouse embryonic stem cells to lympho-hematopoietic lineages in
      vitro.
AB  - Mouse embryonic stem (ES) cells can differentiate in culture to late stages of
      many cell lineages. I have found culture conditions that are favorable for
      development in vitro of ES cells into hematopoietic cells at a stage equivalent
      to day 11-14 of fetal liver development. I describe here: (1) the growth
      conditions necessary for maintenance of ES cells in an undifferentiated state,
      and the conditions that allow differentiation of cystic embryoid bodies that
      contain precursors of most hematopoietic cell lineages, including lymphoid cells;
      (2) the development of lymphoid vessels from ES fetuses in vivo; (3) the
      characterization of lymphoid, erythroid, megakaryoid, and myeloid cells from ES
      fetuses; and (4) the cloning of cell lines representing lymphoid, myeloid lineage
      cells from differentiated ES cells.

PMID- 1355683
TI  - Autologous blood stem cell versus bone marrow transplantation.

PMID- 1355684
TI  - Prevention and therapy of graft-versus-host disease. Report from a work-shop.

PMID- 1355682
TI  - Rationale and results of in utero transplants of stem cells in humans.
AB  - Following 18 years experience in postnatal fetal liver transplantation (FLT), we
      have developed a new therapeutical method, namely the in utero transplantation of
      stem cells from the human fetal liver. This early transplant takes advantage of
      the immunological tolerance that exists in young fetal recipients. The four
      fetuses that we treated were 28, 26, 17 and 12 weeks of age (weeks after
      fecundation). The first two patients had immunodeficiencies, the two other had
      thalassemia major. Donor cells were obtained from 7- to 12-week-old fetuses, with
      conditions approved by the National Committee for Bioethics. Donors and
      recipients were not matched. The fetal cells were infused through the umbilical
      vein of three patients and injected intraperitoneally into the other one, under
      ultrasonic visualization. The first patient, bone in 1988, has evidence of
      engraftment and reconstitution of cell-mediated immunity: initially 10% then 26%
      of lymphocytes of donor origin (with distinct phenotype), T cell responses to
      tetanus toxoid and candida antigens. This child, who had bare lymphocyte
      syndrome, has no clinical manifestation of the disease and lives normally at
      home. The second child was born in 1989; donor cell engraftment has been proven
      (Y chromosome in this female patient) and immunological reconstitution is in
      progress, allowing a normal life at home. The third patient has also evidence of
      donor cell take (Y chromosome in a female patient) and a partial effect on
      thalassemia has been documented (donor haemoglobin present in small quantity). In
      all three cases, no side effect of any kind developed in the mother nor in the
      fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355685
TI  - Autotransplants in myeloma.

PMID- 1355686
TI  - Dose intensive therapy in breast cancer.

PMID- 1355688
TI  - High-dose chemotherapy and stem cell transplantation in solid tumors. Proceedings
      of an international symposium. Berlin, Germany, May 4-6, 1992. Abstracts.

PMID- 1355687
TI  - Use of autotransplants in chronic myeloid leukaemia.
AB  - Patients with newly diagnosed CML have Ph-negative stem cells in their marrow and
      peripheral blood. A minority can be restored to durable Ph-negative haemopoiesis
      by treatment with interferon-alpha but in general autografting with marrow
      collected after IFN treatment has not proved feasible. Some patients autografted
      with blood-derived stem cells collected in chronic phase have achieved durable Ph
      negative haemopoiesis and selected patients autografted with 10-day incubated
      marrow cells have also achieved complete remission. An alternative approach
      involves collection and isolation of Ph-negative stem cells that may then be used
      for autografting. Different lines of evidence suggest that induction of remission
      for all patients with CML should be an attainable goal.

PMID- 1355690
TI  - Abnormal subjective time experience in depression.
AB  - Abnormality of subjective time experience is well recognised in psychiatric
      illness. Earlier authors suggested that slowed time experience in depression is
      an aspect of psychomotor retardation, while more recently it has been argued that
      this disturbance is non-specifically linked to the global severity of the
      depressive syndrome. This study offers evidence that both views can be justified:
      slowed time awareness is a common symptom of depression, related particularly to
      retardation, and to the severity of the mood disturbance. Some of the
      experimental difficulties in this kind of research are illustrated.

PMID- 1355689
TI  - Drug treatment of the personality disorders.
AB  - Many people with well defined borderline and schizotypal personality disorders
      may benefit considerably from small doses of neuroleptics. Depression that occurs
      with personality disorders, which is frequent, responds poorly to tricyclics but
      may respond better to neuroleptics, while the response to ECT is usually short
      lived. Selected borderline subjects may respond to MAOIs, particularly where
      there is a history of childhood hyperactivity. Carbamazepine and lithium may help
      some individuals with episodic behavioural dyscontrol and aggression, even in the
      absence of epileptic, affective or organic features. Drug treatments can be
      combined with psychotherapy, but further placebo-controlled trials are needed to
      clarify which drugs are most useful, and whether there are any useful clinical
      predictors of drug responsiveness.

PMID- 1355691
TI  - Expressed emotion and schizophrenia in Italy. A study of an urban population.
AB  - Forty-two schizophrenic patients and their close relatives took part in an
      Italian replication study of expressed emotion (EE). The patients were selected
      from the psychiatric ward of a general hospital in Milan and were subsequently
      followed up for nine months. All patients attended a community service clinic as
      out-patients, and all but one were prescribed neuroleptics for the duration of
      the study. Relatives were assigned to the high-EE group if they scored 4 or 5 on
      the emotional overinvolvement (EOI) scale, or showed hostility, or made six or
      more critical comments. On this basis, 18 (42%) families were rated as low EE and
      24 (57%) as high EE. At follow-up, the admission rate for the 9-month period was
      significantly higher for the high-EE group (P less than 0.05). Furthermore,
      significantly fewer patients were readmitted from families showing high warmth (P
      less than 0.05). The presence of high warmth appeared to be associated with a
      lower admission rate, even in high-EE families.

PMID- 1355692
TI  - Psychological well-being in families with a member suffering from schizophrenia.
      An investigation into long-standing problems.
AB  - Levels of stress in carers of long-term schizophrenia sufferers attending a depot
      clinic were assessed. Nine out of 25 carers (36%) were identified as possible or
      definite cases on either the GHQ or the HAD. However, a substantial proportion of
      carers managed to cope with the difficulties without suffering psychologically.

PMID- 1355693
TI  - Risk for definite neuroleptic malignant syndrome. A prospective study in 223
      consecutive in-patients.
AB  - The occurrence of neuroleptic malignant syndrome (NMS) was studied prospectively
      in two series of consecutive psychiatric in-patients (n = 223). The first group
      (n = 120) suffered from schizophrenia and was treated only with haloperidol. The
      second group (n = 103) was treated with diverse neuroleptics. All patients were
      on a single antipsychotic agent with no anticholinergic drug as prophylaxis. The
      incidence of full NMS per admission and first neuroleptic exposure was 5/223
      (2.2%). Patients with bipolar affective disorder and those treated with
      injections were significantly over-represented in the NMS group.

PMID- 1355694
TI  - Excitatory amino acid receptors appear to mediate paroxysmal depolarizing shifts
      in rat neocortical neurons in vitro.
AB  - This study was designed to assess some of the contributions of excitatory amino
      acids to locally evoked responses in neurons in slices from frontal motor cortex
      in Sprague-Dawley rats. Intracellular recordings were obtained from 54 cortical
      neurons. Paroxysmal depolarization shifts (PDS) were evoked by local single pulse
      stimulation in cortex or in a small number of cases (n = 2) occurred
      spontaneously. These potentials could be abolished by application of kynurenic
      acid, a broad spectrum excitatory amino acid receptor antagonist. They were
      enhanced in Mg(2+)-free medium and could then be antagonized by application of
      D,L-2-amino-5-phosphonovalerate (AP5), a selective blocker of the N-methyl-D
      aspartate (NMDA) receptors.

PMID- 1355696
TI  - In vivo voltammetric evidence for the detection of norepinephrine release in the
      thalamus of freely moving rats.
AB  - The ventrobasal complex (VB) of the thalamus was monitored in awake rats for the
      presence of norepinephrine (NE) overflow following pharmacological manipulations
      and physiological stimulation. Overflow was detected using chronoamperometry with
      electrochemically pretreated, Nafion-coated carbon fiber microelectrodes. In vivo
      evaluation of the electrode responses to systemic drug administration showed that
      alpha-methyl-p-tyrosine (alpha-MPT) and FLA-63 caused decreases in baseline
      current. Increases in baseline current in the VB were observed in animals treated
      with pargyline, yohimbine and yohimbine injected 2 h postpargyline. The results
      suggest that an electrochemical signal primarily due to NE overflow can be
      monitored in thalamic regions. Vigorous somatosensory stimulation induced small,
      long-lasting (approximately 30 min), reproducible electrochemical signals in the
      VB which were suppressed by alpha-MPT or FLA-63. These studies provide in vivo
      evidence which suggests that stressful somatosensory input to the VB initiates
      the release of NE.

PMID- 1355695
TI  - Domoic acid-containing toxic mussels produce neurotoxicity in neuronal cultures
      through a synergism between excitatory amino acids.
AB  - In 1987, an intoxication by cultured mussels produced neurological problems, such
      as headache, confusion, and loss of memory, particularly severe at times.
      Neuronal damage was found in the hippocampus and amygdala of four patients. The
      intoxication was attributed to the presence in mussels of domoic acid, a rare
      excitatory amino acid acting at the non-NMDA receptor. We now report that a
      domoic acid-containing mussel extract is more neurotoxic for cultured neurons
      than purified domoic acid. Moreover, we show that this increase in neurotoxicity
      is selectively due to domoic acid potentiation of the excitotoxic effect of
      glutamic acid and aspartic acid present in high concentrations in mussel tissue.
      We also show that subtoxic concentrations of domoic acid are sufficient to
      potentiate glutamic acid and aspartic acid neurotoxicity, and we present evidence
      suggesting that the neurotoxic synergism may occur through a reduction of the
      voltage-dependent Mg2+ block at the NMDA receptor-associated channel, following
      activation of non-NMDA receptors by domoic acid. Thus, based on our results, we
      suggest that the contemporary presence in the brain of concentrations of domoic
      acid insufficient alone to be toxic, together with excitatory amino acids, of
      endogenous and eventually of diet-related origin, may have been relevant in the
      occurrence of the neurological problems reported.

PMID- 1355697
TI  - A high percentage yield of tyrosine hydroxylase-positive cells from rat E14
      mesencephalic cell culture.
AB  - In the ventral mesencephalon of the E14 rat fetus, 90% of the dopaminergic,
      tyrosine hydroxylase positive (TH+) cells are localized in 1.0 mm3 of tissue.
      This same ventral mesencephalic region also contains 90% of the dopamine content
      of the E14 ventral brainstem (2.2 +/- 0.3 nmol/mg protein). When cells were
      prepared for culturing from this localized area, and plated at a density of 2.5 x
      10(5) cells/cm2, 17-21% of the cells were TH+, at 4 and 12 h, and at 1, 5, 7 and
      10 days after plating. The percentage of TH+ cells was also 17-21% when examined
      at 4 h, 12 h or 5 days after plating at densities ranging from 7.8 x 10(3) to 2.5
      x 10(5) cells/cm2. However, cell survival at a density of less than 6.2 x 10(4)
      cells/cm2 was poor after 5 days in culture. Based on the degree of neurite
      elongation and complexity, cell maturation appeared to be complete at 5 days in
      culture (DIV5), and appeared to be maintained at this level up to DIV10. By
      DIV14, neurite retraction was evident, and the cells were more rounded. These
      signs may indicate the inception of senescence in the cultures. A benztropine
      sensitive, concentration-dependent dopamine uptake mechanism was demonstrated in
      the cultures at DIV7, and DA could be released from preloaded cells using 50 mM
      K+. Five morphological subtypes of TH+ cells were identified in the cultures.
      This primary culture of the ventral mesencephalic, dopaminergic area, with a high
      percentage of TH+ cells, is suitable for use in acute biochemical and cellular
      studies, between DIV 5 and DIV10.

PMID- 1355698
TI  - Problems associated with the measurement of mean circulatory filling pressure by
      the atrial balloon technique in anaesthetized rats.
AB  - To examine the existence of pressure equilibrium between tributary veins and the
      central vena cava during the mean circulatory filling pressure manoeuvre,
      pressures in the hepatic portal vein, renal vein, and inferior vena cava were
      determined at 4-s intervals over a 20-s period of circulatory arrest induced by
      inflating a right atrial balloon in normal blood volume, 10% volume depletion,
      and 10% volume expansion states in urethane-anaesthetized rats. Portal vein
      pressure determined 8 s after arrest during volume depletion and expansion was
      significantly higher than vena caval pressure (6.2 +/- 0.8 vs. 3.4 +/- 0.2 and
      7.7 +/- 0.5 vs. 6.2 +/- 0.4 mmHg (1 mmHg = 133.32 Pa), respectively; p less than
      0.01); this pressure disequilibrium continued for 16 s during volume expansion
      and for the entire 20 s during volume depletion. Renal vein pressure was equal to
      vena caval pressure during this manoeuvre. Portal vein pressure at normal blood
      volume was not significantly different from vena caval pressure following
      circulatory arrest (4.6 +/- 0.3 vs. 3.8 +/- 0.4 mmHg, respectively). Following
      ganglionic blockade, portal vein pressure was still significantly higher than
      vena caval pressure for 12 s during volume alterations. At the 8th s of the
      arrest the portal pressure determined in volume depletion was 3.6 +/- 0.3 mmHg
      and the inferior vena caval pressure was 2.6 +/- 0.4 mmHg (p less than 0.05).
      Under the volume expansion condition, the respective values were 6.5 +/- 0.3 and
      5.3 +/- 0.4 mmHg (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355700
TI  - The benzodiazepines in dentistry: a review.

PMID- 1355699
TI  - Cocaine-enhanced arrhythmogenesis: neural and nonneural mechanisms.
AB  - Cocaine abuse increases the susceptibility to cardiovascular complications and
      sudden cardiac death in man. We used programmed electrical stimulation of the
      heart to examine the arrhythmogenic influence of cocaine. Twenty-three
      pentobarbital-anesthetized adult dogs underwent programmed electrical stimulation
      using one to four extrastimuli before and during cocaine infusion. Autonomic
      decentralization was performed prior to the protocol in eight dogs. Induced
      ventricular arrhythmias included single premature ventricular depolarizations,
      doublets, triplets, ventricular tachycardia, and ventricular fibrillation.
      Intravenous cocaine, and subsequent adrenergic and muscarinic receptor blockade,
      or calcium channel blockade were evaluated for their influence on
      arrhythmogenesis. The incidence of induced ventricular arrhythmias was
      significantly elevated following cocaine and was reduced following propranolol
      and atropine. Verapamil, however, did not reduce the incidence of induced
      arrhythmias. In addition, cocaine significantly increased arrhythmia induction in
      decentralized animals, but propranolol, atropine, and phentolamine failed to
      reduce the proarrhythmic effects of cocaine in these animals. Thus, cocaine has a
      proarrhythmic effect on the heart with multiple mechanisms. The adrenergic
      mechanism appears to be a result of neurotransmitter uptake blockade, whereas the
      likely ionic mechanism is a neurally independent, direct effect on the heart.

PMID- 1355701
TI  - A coupled assay detecting defects in fibroblast isoleucine degradation distal to
      enoyl-CoA hydratase: application to 3-oxothiolase deficiency.
AB  - We developed a coupled NaH14CO3 fixation assay to detect 3-oxothiolase deficiency
      in extracts of cultured human fibroblasts. Cell extracts were incubated with
      tiglyl-CoA, NAD, CoASH, ATP and NaH14CO3. The enzymatic activities of tiglyl-CoA
      (enoyl-CoA) hydratase, 2-methyl-3-hydroxybutyryl-CoA dehydrogenase and 2
      methylacetoacetyl-CoA thiolase (3-oxothiolase) were coupled to produce propionyl
      CoA. Propionyl-CoA produced in the assay was estimated by fixation of NaH14CO3
      into [14C]methylmalonyl-CoA employing endogenous propionyl-CoA carboxylase. The
      control activity was 32 +/- 23 pmol/min per mg protein (+/- 1 S.D., range 7-94;
      28 cell lines). Five known cases of 3-oxothiolase deficiency had a mean activity
      of 2% of the control; a sixth case of 3-oxothiolase deficiency was significantly
      higher at 27% of the mean control value. Coupled assay activity was also low (3%
      of control) in the cells from a patient with propionyl-CoA carboxylase
      deficiency.

PMID- 1355703
TI  - Tay-Sachs disease as a model for screening inborn errors.
AB  - In the absence of treatments for most inborn errors of metabolism, the goal of
      both geneticists and health care providers has been the prevention of disease
      through identification of at-risk couples. When the enzyme deficiency responsible
      for a disorder is known, heterozygotes can frequently be identified by enzyme
      assay. The presence or absence of specific mutations in the genes coding for
      these enzymes may be determined directly if the gene of interest has been
      identified and characterized. Because the inherited metabolic disorders are rare,
      these approaches are useful only for individuals with a family history of a
      specific disease or for populations in which the gene frequency for a specific
      disease is increased. Tay-Sachs disease is a fatal, autosomal recessive,
      metabolic disease caused by deficient activity of the lysosomal enzyme Hex A.
      Although it is rare in the general population, in which the heterozygote
      frequency is approximately 1/167, it is elevated in a few populations, including
      the Ashkenazi Jewish community, in which the heterozygote frequency is 1/30. The
      ability to detect TSD heterozygotes reliably and to diagnose TSD prenatally using
      a simple and rapid enzyme assay has made prevention of this disorder possible
      through education and carrier screening. The identification of specific TSD
      mutations at the DNA level enables laboratories to provide more accurate
      screening and diagnosis in some families. The success of TSD screening in the
      Ashkenazi Jewish population has made it the prototype for screening among the
      inborn errors of metabolism. The TSD example becomes increasingly relevant as
      heterozygote detection becomes possible for other genetic disorders that are
      increased in well-defined populations. Cystic fibrosis is such a disease in the
      caucasian population.

PMID- 1355702
TI  - Polymorphisms of candidate genes in essential hypertension.
AB  - 1. Family and population studies have reported that blood pressure has a
      heritability of 30-50%, but simple genetic models do not readily explain the
      patterns of inheritance of hypertension. 2. Restriction fragment length
      polymorphisms were used to study allele frequencies of a selection of candidate
      genes that may be important in determining the genetic component of hypertension.
      These included the genes for renin, haptoglobin, neuropeptide Y and cardiac
      myosin beta heavy chain. 3. There was no significant association between alleles
      at any of these loci and the presence of hypertension in this population,
      suggesting that the contribution of variation at these loci to the genetic
      component of the variance in hypertension may be quite small.

PMID- 1355704
TI  - Technical progress in parentage analysis.
AB  - At the turn of the 20th century, Mendel's laws were found to be applicable to
      human blood groups. Within two decades, blood group genetics were applied to
      problems of parentage. Expansion of immunohematology into leukocyte antigen
      identification produced the single most informative, expressed polymorphism.
      About the same time, analysis of a great number of soluble protein polymorphisms
      followed advances in electric separation methods, enzymology, and
      immunochemistry. As new, independent loci were discovered, the power to exclude
      the falsely accused increased, and it became possible to apply Bayesian
      principles to determined probabilities of biologic relationships. The revolution
      in nucleic acid technology has dramatically improved analysis and statistical
      inferences. By the turn of the 21st century, laboratories should be able to
      determine biologic parentage with virtual certainty.

PMID- 1355705
TI  - Hemodynamic effects of dobutamine in an intact animal model.
AB  - BACKGROUND AND METHODS: Actions of dobutamine at the beta 1, beta 2, and alpha 1
      adrenoreceptors were studied in anesthetized dogs. Six animals received
      dobutamine (at infusion rates of 0 to 160 micrograms/kg/min) with and without
      beta-adrenergic receptor blockade. Five animals received phenylephrine (0 to 16
      micrograms/kg/min), with and without concurrent dobutamine (20
      micrograms/kg/min); this procedure was repeated in five animals after beta
      blockade. RESULTS: Dobutamine (10 to 160 micrograms/kg/min) increased heart rate
      (HR), cardiac output, and left ventricular change in pressure over time, and
      decreased systemic vascular resistance. beta-blockade prevented only dobutamine
      induced changes in HR. Mean arterial pressure (MAP), unaffected by dobutamine
      alone, decreased with concurrent beta-blockade. Phenylephrine (1 to 16
      micrograms/kg/min)-induced increases in MAP were unaffected by dobutamine; with
      beta-blockade, phenylephrine reduced MAP. Dobutamine prevented a phenylephrine
      induced increase in systemic vascular resistance, an effect eliminated by beta
      adrenergic receptor blockade. CONCLUSIONS: Dobutamine appeared to be an agonist
      at the beta 1- and beta 2-adrenoreceptors and at the myocardial alpha
      adrenoreceptor. Dobutamine appeared to be an alpha-adrenergic receptor antagonist
      in the peripheral vasculature.

PMID- 1355706
TI  - The effects of age on glutathione synthesis enzymes in lenses of Old World
      simians and prosimians.
AB  - The activities of gamma-glutamylcysteine synthetase and glutathione synthetase,
      the two enzymes required for glutathione synthesis, were determined as a function
      of age in lenses of three species of Old World higher primates: orangutan,
      pigtail monkey and olive baboon. These were compared to enzyme activities in
      lenses of two prosimians: mouse lemur and galago. gamma-Glutamylcysteine
      synthetase activity decreased as a function of age in all three Old World
      simians. The rate of decrease was greatest in the juvenile lenses. In contrast,
      the enzyme activity increased continuously with age in the galago lens. In the
      mouse lemur the enzyme activity increased per lens, but was constant when
      expressed as specific activity or as units per gram of lens. The loss of enzyme
      activity with age was limited to Old World higher primates apparently
      representing genetic change. Glutathione synthetase activity decreased
      logarithmically with age in the lenses of all five species.

PMID- 1355707
TI  - Stereoselective disposition of S-8666, a novel uricosuric antihypertensive
      diuretic, and its N-monodemethylated metabolite in a perfused rat liver
      preparation. Effect of protein binding on the kinetics of S-8666.
AB  - S-8666 (5-dimethyl-sulfamoyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxylic
      acid), a novel uricosuric antihypertensive diuretic, and its N-monodemethylated
      metabolite (M-I) were studied in a single pass perfused rat liver preparation
      under constant perfusate flow (ca. 16 ml/min). During perfusion with 100 nmol/ml
      of racemic S-8666 not containing bovine serum albumin (BSA), the steady-state
      hepatic extraction ratio of R(+)-S-8666 was two times higher (0.65 +/- 0.08) than
      that of S(-)-S-8666 (0.34 +/- 0.08). R(+)- and S(-)-M-I in the effluent perfusate
      plasma accounted for 64 and 18% of the influx rate of each enantiomeric S-8666,
      respectively. The N-monodemethylation was found to be responsible for the hepatic
      extraction of S-8666 enantiomers. S(-)-S-8666 was excreted into bile at a more
      rapid rate than the R(+)-enantiomer. Biliary excretion of R(+)-M-I was faster
      than S(-)-M-I, although the excretion rates of M-I were slower than those of S
      8666 for both enantiomers. The steady-state extractions of preformed R(+)- and S(
      )-M-I were low and a significant difference [S(-) greater than R(+)] was observed
      during the perfusion of 100 nmol/ml preformed racemic M-I without BSA. Increasing
      the concentration of BSA in the perfusate led to decreases in the extraction
      ratios of S-8666 enantiomers and biliary excretion rates of all chemicals, which
      was due to the decreases in the free fractions of S-8666 and M-I enantiomers. The
      binding of S-8666 and M-I enantiomers to BSA also showed stereoselectivity [R(+)
      less than S(-)].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355708
TI  - Diphenyl ether cleavage of 3-phenoxybenzoic acid by chicken kidney microsomal
      preparations.
AB  - Incubation of 3-phenoxybenzoic acid[carbonyl-14C] with chicken kidney microsomal
      fraction produced two major radioactive compounds identified as 3-hydroxybenzoic
      acid and 4'-hydroxy-3-phenoxybenzoic acid. It was found that 4'-hydroxy-3
      phenoxybenzoic acid was transitory in nature and was rapidly converted into 3
      hydroxybenzoic acid. The conversion of 3-phenoxybenzoic acid to the products was
      NADPH dependent. This is a first example of metabolism of 4'-hydroxy-3
      phenoxybenzoic acid to 3-hydroxybenzoic acid. Cytosol did not promote any
      cleavage. Similar activities were present in liver microsomes, but the activity
      was lower than in kidney. Intestinal contents, homogenates, or microsomal
      fractions did not metabolize 3-phenoxybenzoic acid.

PMID- 1355709
TI  - Purification and characterization of a cytochrome P-450 isozyme catalyzing
      bunitrolol 4-hydroxylation in liver microsomes of male rats.
AB  - A cytochrome P-450 isozyme, P-450 bunitrolol (BTL), catalyzing bunitrolol 4
      hydroxylation was partially purified from liver microsomes of adult male Sprague
      Dawley rats by hydrophobic affinity chromatographic (omega-aminooctyl-Sepharose
      4B) and high-performance liquid chromatographic (anion-exchange diethylaminoethyl
      5PW) techniques. The specific content of the final preparation was 5.02 nmol/mg
      protein, which was 7.8-fold that of microsomes. It showed two protein bands of 49
      and 32 kDa in sodium dodecylsulfate-polyacrylamide gel electrophoresis. N
      Terminal 20 amino acid sequence of the protein of a higher molecular mass (49
      kDa) isolated by an electroblotting technique is 94% homologous with that of
      CYP2D2. In a reconstituted system including NADPH-cytochrome P-450 reductase and
      an NADPH-generating system, the final preparation had the highest activity toward
      BTL and debrisoquine 4-hydroxylation among 12 isozymes of cytochrome P-450
      examined. Kinetic parameters, KM and Vmax values, of P-450 BTL calculated for BTL
      4-hydroxylation were 10.7 microM and 19.68 nmol/min/nmol P-450, respectively,
      whereas those values (mean +/- SE) of rat liver microsomes were 0.84 +/- 0.05
      microM and 2.05 +/- 0.11 nmol/min/nmol P-450. When preincubated with rat liver
      microsomes, the antibody against the final P-450 BTL preparation suppressed
      bunitrolol and debrisoquine 4-hydroxylase activities dose-dependently and almost
      completely. These results suggest that cytochrome P-450 BTL and its
      immunochemically related P-450 isozyme(s) play a major role in debrisoquine 4
      hydroxylation as well as in BTL 4-hydroxylation in rat liver microsomes.

PMID- 1355710
TI  - Homeostasis of sulfate and 3'-phosphoadenosine 5'-phosphosulfate in rats with
      deficient dietary intake of sulfur.
AB  - This study was designed to determine the role of dietary organic and inorganic
      sulfur on 3'-phosphoadenosine 5'-phosphosulfate (PAPS) homeostasis. Organic
      sulfur was altered by adding various amounts of methionine (0.15, 0.3, 0.6, or
      1.2%) to a sulfhydryl-deficient diet. Inorganic sulfur was altered by providing
      rats with no sulfate or sulfate in their diets (0.12%) and distilled or tap
      water. Rats received these diets for 5 days. The two lowest methionine-containing
      diets produced a 60% reduction in liver glutathione concentrations, and the
      addition of sulfate to the diets did not restore hepatic glutathione levels.
      Urinary sulfate excretion was reduced by 95% in rats fed the three low-methionine
      diets. Addition of sulfate to these diets increased the urinary excretion of
      sulfate, but did not return sulfate levels to control values. The three low
      methionine-containing diets decreased serum and liver sulfate concentrations
      about 50% and addition of sulfate to these diets largely restored them to control
      levels. Hepatic PAPS concentration was decreased (10%) only in the group
      receiving the lowest methionine content in their diet, and addition of sulfate
      had no effect on hepatic PAPS. In summary, dietary alterations of sulfur lowered
      the glutathione concentration in the liver as well as decreased sulfate levels in
      serum, liver, and urine, but had minimal effect on hepatic PAPS concentrations.
      Therefore, it appears that hepatic steady-state PAPS levels are not highly
      dependent on the sulfur content of the diet.

PMID- 1355711
TI  - Inhibition of debrisoquin clearance in perfused rat livers and inhibition of
      dextromethorphan metabolism in human liver microsomes by 4-hydroxydebrisoquin or
      other metabolites of debrisoquin.
AB  - Debrisoquin undergoes oxidative metabolism to 4-hydroxydebrisoquin, catalyzed by
      cytochrome CYP2D1 in rats and CYP2D6 in humans. Cytochrome CYP2D6 also plays a
      major role in dextromethorphan O-demethylation. In preliminary studies in
      perfused Lewis rat livers, we observed a difference in repeat clearance
      experiments using debrisoquin, but not dextromethorphan. To determine whether
      this change in clearance with time was due to the accumulation of 4
      hydroxydebrisoquin, we sequentially used a recirculating and nonrecirculating
      perfusion system in the same liver perfusion experiment. We also studied the
      kinetics of dextromethorphan O-demethylation in microsomes prepared from human
      and rat livers in the presence and absence of 4-hydroxydebrisoquin. Results from
      the perfused rat liver experiments showed a drop in clearance from 3.27 +/- 0.57
      ml/min (clearance 1) to 1.61 +/- 0.27 ml/min (clearance 2) (p less than 0.05 vs.
      clearance 1) during recirculation, but clearance returned to 3.21 +/- 0.46 ml/min
      (clearance 3, no significance vs. clearance 1) after a 30-min period of liver
      perfusion using a nonrecirculating system. There was significant accumulation of
      4-hydroxydebrisoquin in the liver perfusate during recirculation, and
      concentrations fell when the nonrecirculating system was used. In microsomal
      studies, 4-hydroxydebrisoquin competitively inhibited dextromethorphan metabolism
      in human microsomes was 600 microM. These data suggest that: (a) 4
      hydroxydebrisoquin and/or other metabolites of debrisoquin have an inhibitory
      effect on CYP2D1 and CYP2D6; (b) the active site of human CYP2D6 has different
      substrate specificity than the rat isozyme (CYP2D1) and/or that the pathways of
      metabolism of dextromethorphan are different in the Lewis rat and not primarily
      dependent on the activity of CYP2D1.

PMID- 1355712
TI  - In vitro and in vivo biotransformations of the potent leukotriene D4 antagonist
      verlukast in the rat.
AB  - Verlukast, (S)3-((((3-(2-(7-chloroquinolin-2-yl)-(E)-ethenyl)phenyl)- 3
      dimethylamino-3-oxopropylthio)methyl)thio)propionic acid, formerly known as MK
      679, is a potent leukotriene D4 antagonist. Verlukast was incubated with rat
      liver microsomes under oxidative conditions to generate five metabolites, which
      were identified as the four possible isomeric monosulfoxides (M1-M4), and the N
      hydroxymethyl amide (M5). This latter metabolite loses the elements of
      formaldehyde to yield the N-monomethyl amide (M6). These metabolites were
      isolated from a large microsomal incubation and were characterized by UV, 1H-NMR,
      and fast atom bombardment-MS. These data were identical to those obtained from
      synthetically prepared standards. Microsomal incubations of verlukast
      supplemented with UDP-glucuronic acid yielded the acyl glucuronide metabolite
      (M7), which was isolated and characterized by UV, 1H-NMR, and fast atom
      bombardment-M5. Verlukast was regenerated from M7 upon treatment with either beta
      glucuronidase or strong aqueous base (pH greater than 11). The metabolites
      described above were all detected in bile collected from a rat dosed with
      verlukast.

PMID- 1355714
TI  - Pharmacokinetic evaluation of drug interactions with anti-human immunodeficiency
      virus drugs. V. Effect of soluble CD4 on 2',3'-dideoxycytidine kinetics in
      monkeys.
AB  - This study was conducted to determine if soluble CD4 (ST4) altered the
      pharmacokinetics of 2',3'-dideoxycytidine (ddC) in nonhuman primates. Each of six
      monkeys received 5 mg/kg of ddC iv in the absence and presence of two different
      iv regimens of ST4. The ST4 regimens produced steady-state plasma concentrations
      of 10.3 micrograms/ml (N = 3) and 22.2 micrograms/ml (N = 3) for 30 min following
      ddC administration. Pharmacokinetic parameters for ddC and ST4 were calculated
      based on plasma and urine concentrations of ddC and plasma concentrations of ST4.
      Following combined ddC and ST4 administration, in both the low- and high-dose ST4
      groups, plasma concentration-time profile of ddC were similar for each monkey,
      and no statistical differences were observed in the pharmacokinetic parameters
      compared with those obtained when ddC was given alone. Complete urinary excretion
      data for ddC was obtained in 3 of the 6 animals studied. At the low ST4 dose, one
      animal had a reduced renal clearance of ddC, whereas at the high ST4 dose two
      animals recorded an increased renal clearance of ddC. ST4 plasma concentrations
      were comparable to in vitro concentrations of antiviral activity, with
      pharmacokinetic parameters similar to those reported previously. The kinetic
      information provides a basis for rational dosage design for combination
      chemotherapeutic regimens of ddC and ST4 in human immunodeficiency virus
      infection.

PMID- 1355713
TI  - Physiological disposition and metabolism of L-365,260, a potent antagonist of
      brain cholecystokinin receptor, in laboratory animals.
AB  - L-365,260 [3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepine-3
      yl)-N'-(3-methylphenylurea)], a potent nonpeptide antagonist of the CCKB
      receptor, is currently under investigation to treat anxiety and panic disorders.
      This study describes absorption and disposition of the drug in rats, dogs, and
      monkeys. Following iv administration (5 mg/kg), L-365,260 was cleared very
      rapidly in rats, dogs, and monkeys. In all species, the concentrations of the
      drug in plasma declined in a polyphasic manner. There was no difference in total
      blood clearance among species, whereas considerable species differences were
      observed in volume of distribution and terminal half-lives. Binding of 14C-L
      365,260 to plasma protein was extensive for all test species (greater than 96%).
      Interspecies differences in absorption were also observed. The bioavailability
      for rats, dogs, and monkeys was approximately 14%, 9%, and 2%, respectively. HPLC
      radiohistograms of urine and bile revealed that only trace amounts of intact drug
      were present; the drug was mainly eliminated by biotransformation. NMR and mass
      spectral analyses indicate that hydroxylation and glucuronide conjugation are the
      major biotransformation pathways.

PMID- 1355715
TI  - Obesity as a risk factor in drug-induced organ injury. V. Toxicokinetics of
      gentamicin in the obese overfed rat.
AB  - Obese human patients and obese overfed rats treated chronically with gentamicin
      suffer greater renal injury than nonobese patients and control animals. To
      understand the mechanism of this heightened susceptibility to the nephrotoxic
      effects of gentamicin, this study examines the plasma-time course and renal
      uptake of gentamicin in control and obese overfed rats following a single bolus
      dose. Gentamicin was administered ip to control rats at 30 mg/kg total body mass
      and to obese rats at 30 mg/kg ideal body mass plus 40% of excess body mass.
      Following gentamicin dosing, only 1 of 11 concentration-time points taken over
      6/hr postdosing was different between control and obese groups. In addition, the
      area under the plasma concentration curve extrapolated to infinite time was not
      different between obese and control rats (mean +/- SD of 4.47 +/- 0.85 vs. 4.13
      +/- 0.35 mg.min.ml-1, p greater than 0.5). The gentamicin plasma concentrations
      after 6 hr were less than 1 microgram/ml and not different between the groups;
      however, the concentration of gentamicin in the kidneys was 33% greater in obese
      than control rats at this time (324 +/- 66.9 vs. 244 +/- 34.7 micrograms/g, p
      less than 0.05). The fraction of dose and the total amount of drug that
      accumulated in the kidneys were also greater in the obese rats (42 and 72%
      increases). Considered with the results of previous studies, it appears that
      obese overfed rats sustain more severe nephrotoxicity following comparable plasma
      gentamicin exposure because of increased renal uptake and/or retention of drug.

PMID- 1355717
TI  - Sulfation of estrone and 17 beta-estradiol in human liver. Catalysis by
      thermostable phenol sulfotransferase and by dehydroepiandrosterone
      sulfotransferase.
AB  - Sulfation is a major pathway in humans for the biotransformation of estrogens.
      However, the nature of the enzymes that catalyze the sulfation of estrone (E1)
      and 17 beta-estradiol (E2) in human liver is unclear. Human liver contains at
      least three well-characterized cytoplasmic sulfotransferases, the thermostable
      (TS) and thermolabile (TL) forms of phenol sulfotransferase (PST) and
      dehydroepiandrosterone sulfotransferase (DHEA ST). Therefore, we determined
      optimal conditions for the assay of E1 and E2 ST activities in human hepatic
      cytosol to compare their properties and regulation with those of the three well
      characterized human liver ST activities. Thermal inactivation studies showed that
      human liver E2 ST and TS PST had very similar thermal stabilities. The thermal
      inactivation profile of E1 ST suggested that this activity might be related to
      both DHEA ST and TS PST. Inhibition studies performed with 2,6-dichloro-4
      nitrophenol (DCNP) also showed similar inhibition profiles for E2 ST and TS PST.
      Neither thermal inactivation nor DCNP inhibition studies indicated a possible
      relationship between TL PST activity and E1 or E2 sulfation. Experiments
      performed with 20 individual human liver samples showed highly significant
      correlations between activity levels of E2 ST and TS PST (rs = 0.944, p less than
      0.0001), E1 ST and DHEA ST (rs = 0.845, p less than 0.0001), and, to a lesser
      degree, E1 ST and TS PST (rs = 0.608, p less than 0.01). Ion exchange
      chromatography of a human liver preparation, followed by assay of all five ST
      activities, confirmed the important roles played by TS PST and DHEA ST in the
      sulfation of E2 and E1. Similar results were found by study of the elution
      patterns of ST activities after ion exchange chromatography of human jejunal
      mucosal preparations. Partially purified TL PST, however, was unable to catalyze
      the sulfate conjugation of either E1 or E2. All of these results were compatible
      with the conclusion that, in human liver, TS PST is the enzyme predominantly
      responsible for the sulfate conjugation of E2, DHEA ST is the major enzyme
      responsible for the sulfation of E1, and TL PST does not appear to catalyze the
      sulfation of either E1 or E2.

PMID- 1355716
TI  - Differential effects of human recombinant interleukin-1 beta on cytochrome P-450
      dependent activities in cultured fetal rat hepatocytes.
AB  - The immunomodulator interleukin-1 beta (IL-1) is one of the major inflammatory
      mediators. In vivo, it has been reported to depress some rat liver cytochromes P
      450 (cytochrome P-450). Our aim was to study those effects in vitro, using
      cultured fetal rat hepatocytes as a model. Testosterone 6 beta-hydroxylase
      (cytochrome P-450 IIIA family activity) was not depressed by IL-1 treatments, but
      its induction by dexamethasone was prevented. The effect was time- and dose
      dependent. Ethoxyresorufine-O-deethylase (cytochrome P-450 IA1 activity)
      decreased after IL-1 treatment, and dexamethasone partially prevented this
      inhibition. Acute phase effects of IL-1 were assayed by albumin and transferrin
      secretions. The cell's sensitivity to glucocorticoids was determined by tyrosine
      aminotransferase activity. Our data demonstrate that IL-1 was able to prevent the
      glucocorticoid induction of cytochrome P-450 IIIA involving at least two
      different mechanisms. This is in agreement with the theory suggesting that the
      induction of CYPIIIA family by glucocorticoids requires the presence of the
      glucocorticoid receptor and some other regulatory elements. Other cytochrome P
      450-dependent activities (IIA1, IIB1/2, and IIC11) were inhibited by IL-1
      treatments, depending on dose and time, but some were also protected by
      dexamethasone.

PMID- 1355718
TI  - Tissue concentrations of coenzyme Q10 in the rat following its oral and
      intraperitoneal administration.
AB  - Daily oral or ip administration of coenzyme Q10 to rats for time periods of 2 to
      10 weeks leads to its accumulation in liver, concentrating in the soluble
      fraction of the liver cells. No uptake of coenzyme Q10 can be detected in the
      heart or kidney. Intraperitoneal administration also results in the accumulation
      of coenzyme Q10 in the spleen. It is concluded that the normal endogenous levels
      of quinone in the rat heart and kidney cannot be supplemented over the long term
      by administration of exogenous quinone.

PMID- 1355720
TI  - Disposition kinetics of amphotericin B in rats. The influence of dose.
AB  - Amphotericin B (Am-B), an antifungal drug, has been used for the treatment of
      most disseminated fungal infections. The current therapeutic regimens for this
      drug are complex, at least in part as a result of limited pharmacokinetic
      information. In this study, we examined the disposition of Am-B as a function of
      dose in rats. Groups of male Sprague-Dawley rats were given Am-B by a 15-min iv
      infusion at three different doses. We observed no significant differences in
      systemic clearance among the Am-B doses studied (4.29 +/- 1.42, 3.83 +/- 0.29,
      and 3.92 +/- 0.68 ml/min.kg for doses of 0.28, 0.45, and 0.84 mg/kg,
      respectively). Similarly, small differences were seen in volumes of distribution
      as a function of dose. We conclude that the disposition kinetics of Am-B were
      linear over the dose range studied.

PMID- 1355719
TI  - Physiological disposition of aerosolized MK-679 in rats.
AB  - [14C]MK-679, a potent antagonist of leukotriene D4, was suspended in freon under
      pressure and sprayed into rat lungs through a tracheal cannula. The particle size
      of the drug was 1 to 5 microns, and the mean dose was 98.8 +/- 4.46
      micrograms/rat. Time course studies indicate that MK-679 was slowly but
      efficiently absorbed from the lung, with only 6% of the dose remaining in the
      lung at 6 hr. Biliary excretion, the major route of elimination of aerosolized MK
      679, accounted for 48% of the dose in 6 hr. Concentrations of the parent drug
      plateaued in plasma at 1 to 4 hr, and drug was not detectable in plasma at 6 hr.
      The parent drug accounted for 94% of the radioactivity in the lung, indicating no
      significant metabolism by lung tissue. The concentration of MK-679 after aerosol
      administration was higher in the lung and lower in plasma than after iv
      administration of the drug at 28 times the aerosol dose. The results of this
      study suggest that inhalation of MK-679 should be a considered route of
      administration for the treatment of asthma.

PMID- 1355721
TI  - Effect of dose on the percutaneous absorption of 2- and 4-chloronitrobenzene in
      rats.
AB  - The effect of dose on the dermal absorption of 2- and 4-chloronitrobenzene (2-
      and 4-CNB) has been investigated in rats following nonocclusive protective dermal
      application on an area of 4 cm2 per animal at approximately 0.0325, 0.325, and
      3.25 mg/cm2 (0.65, 6.5, and 65 mg/kg, respectively). At the three-dose levels, 33
      40% and 51-62% of the dose of 2- and 4-CNB, respectively, was absorbed from the
      skin within 72 hr. The balance of the dose was recovered in the protective device
      and the organic trap (i.e. that portion unavailable for dermal absorption). The
      absorbed radioactivity was excreted in urine (21-28% of dose, 2-CNB; 43-45%, 4
      CNB) and feces (11-15%, 2-CNB; 5-12%, 4-CNB). The extent and rate of dermal
      absorption and urinary and fecal excretion of 2-CNB were linear over the 0.65-65
      mg/kg dose range; for 4-CNB they were linear over the 0.65-6.5 mg/kg dose, and
      nonlinear at the 65 mg/kg dose.

PMID- 1355722
TI  - Cytochrome P-450 in the brain. Potential evolutionary and therapeutic relevance
      of localization of drug-metabolizing enzymes.
AB  - The cytochrome P-4502D6 enzyme is reportedly expressed in the brain. It was
      hypothesized that brain P-450 may serve to diminish exposure and toxicity from
      exogenous substances by enhancing their elimination from the central nervous
      system (CNS). To test this, a physiologic-based kinetic model was developed to
      simulate drug concentrations in brain and blood in the presence and absence of
      CNS metabolism. The amount of cytochrome P-450 in the brain was set at 0.25% of
      hepatic levels to reflect the small amounts of enzyme reportedly present in the
      CNS. Simulations were performed for low, intermediate, and high clearance drugs,
      assuming the presence or absence of brain P-450 enzymes. Enzyme localization was
      simulated by systematically reducing the volume into which the enzyme was
      expressed. No difference could be detected in drug concentrations in the blood,
      regardless of whether enzyme was present and/or localized in brain tissue. Marked
      differences, however, were observed in steady-state tissue drug levels that were
      highly dependent on the presence or absence of the brain enzyme, its degree of
      localization, and its efficiency for its substrate. These results suggest that
      large intersubject variability in CNS response to some drugs could reflect
      interpatient differences in CNS drug metabolism.

PMID- 1355723
TI  - Isolation and characterization of carbinolamide and phenolic glucuronide
      conjugates of (+-)-N-methyl-N-(1-methyl-3,3-diphenylpropyl) formamide and N
      formylmethamphetamine by FAB/MS, LC/MS/MS, and NMR.
AB  - The metabolic disposition of (+-)-N-methyl-N-(1-methyl-3,3- diphenyl
      propyl)formamide, especially with regard to the formation of water soluble
      glucuronides, is described. The glucuronide conjugates, (+-)-N-hydroxymethyl-N-(1
      methyl-3,3-diphenylpropyl)formamide glucuronide, (+-)-N-methyl-N-[1-methyl-3-(4'
      hydroxyphenyl)-3-phenylpropyl]formamide glucuronide, and (+-)-N-methyl-N-[1
      methyl-3-(4'-hydroxy-3'-methoxyphenyl)-3- phenylpropyl]formamide glucuronide were
      isolated from the bile of rats dosed with the parent compound. These conjugates
      were characterized spectroscopically by 1H-NMR, FAB/MS, and LC/MS/MS. Because it
      is becoming more common to isolate the intact glucuronide conjugates of
      xenobiotics, we investigated some common mass spectral fragmentation patterns of
      these conjugates, especially by LC/MS/MS. The fragmentation patterns for each of
      the conjugates were obtained under MS/MS conditions and compared. Specifically,
      the fragmentation patterns of phenolic glucuronide and an aliphatic O
      glucuronide, in particular a carbinolamide glucuronide, were investigated. The
      data obtained from these studies was used to predict the nature of glucuronide
      conjugates obtained from rats dosed with the formamide analog, N
      formylmethamphetamine. This is the first spectroscopic characterization of an
      intact carbinolamide glucuronide conjugate isolated from the bile of rats.

PMID- 1355724
TI  - Influence of dibutyryl-cAMP on ibuprofen-induced alterations of sulfate renal
      clearance in rats.

PMID- 1355725
TI  - Carbonyl (phenone) reductase in human liver: structure-activity relationship
      among substrates.

PMID- 1355727
TI  - Glucosidation as a new conjugation pathway for metabolites of bis(2-ethylhexyl)
      phthalate.

PMID- 1355726
TI  - Distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin in splenic tissue of C57BL/6J
      mice.

PMID- 1355728
TI  - Treatment of acromegaly with dopamine agonists.
AB  - This article reviews the current understanding of how dopamine agonists stimulate
      growth hormone secretion in normal individuals, yet suppress growth hormone
      secretion in acromegaly patients. Although bromocriptine normalizes growth
      hormone or somatomedin C hypersecretion in a minority of patients, a significant
      number of subjects have a clinical response. Side effects of bromocriptine
      treatment and newer dopamine agonists are discussed. These drugs can be useful
      medical therapy, either used alone in selected patients or in combination with
      other therapeutic modalities.

PMID- 1355729
TI  - Somatostatin analogs in the treatment of acromegaly.
AB  - Medical therapy of acromegaly with the somatostatin analog octreotide is very
      successful. Both clinical symptomatology and hormonal hypersecretion by the
      growth hormone-secreting pituitary adenomas are controlled, and peripheral IGF-I
      levels also return to near normal levels. Tumor shrinkage is observed in most
      patients. Somatostatin analogs can be used after noncurative surgery and for a
      limited period after radiotherapy, and octreotide pretreatment might improve the
      outcome of surgery.

PMID- 1355730
TI  - Changes in calpain and calpastatin mRNA induced by beta-adrenergic stimulation of
      bovine skeletal muscle.
AB  - Administration of beta-adrenergic agonists to mammals can produce skeletal muscle
      hypertrophy in some species and muscle types. The growth-promoting effect appears
      to be due to suppression of protein breakdown rather than stimulation of
      synthesis, although evidence from turnover studies is equivocal. In ovine muscle,
      changes in the activity of the calcium dependent neutral proteinases (calpains I
      and II) and their specific inhibitor (calpastatin) accompany beta-agonist-induced
      hypertrophy. These observations suggest that the calpain system is involved in
      myofibrillar protein turnover in some way. Alternatively, the relationship with
      hypertrophy may be indirect, since the calpains also interact with hormone and
      growth-factor receptors, protein kinase C and transcription factors, in addition
      to a range of membrane, cytoskeletal and nuclear proteins. In the present study,
      attempts have been made to determine if the beta-agonist-induced effects on the
      calpain system are associated with corresponding changes in specific mRNA. The
      activity of both calpain isoforms and calpastatin was measured in bovine
      longissimus dorsi samples from trials in which test animals were treated with the
      beta agonist cimaterol. Total RNA was extracted from the muscle samples. A cDNA
      probe for calpastatin mRNA was generated from bovine RNA by the polymerase chain
      reaction. This cDNA and a human calpain-II large-subunit cDNA were used to detect
      specific mRNA by Northern-blot analysis. beta-agonist treatment of Friesian
      steers caused significant longissimus dorsi hypertrophy. Increases in muscle mass
      (+37%, P less than 0.005), calpain-II specific activity (+27%, P less than 0.05)
      and calpastatin-specific activity (+76%, P less than 0.05) were found in treated
      animals. Total RNA was unchanged, but there was a 96% overall increase in
      calpastatin mRNA and a 30% increase in calpain-II large-subunit mRNA in muscle
      from treated animals. The mRNA changes are similar in direction and degree to the
      activity changes. Both calpain-II large subunit and inhibitor expression may
      therefore be stimulated by agonist action at the level of transcription or mRNA
      stabilisation. Multiple calpastatin mRNA species were detected in steers, as
      reported for other species. Differential changes in these messages, induced by
      the beta agonist, suggest that expression or stability of alternative mRNA
      species may be a factor in calpastatin regulation.

PMID- 1355732
TI  - Interference of azelastine with anaphylaxis induced by ovalbumin challenge in
      actively sensitized rats.
AB  - The inhibition of the haematological alterations and prevention of death due to
      systemic anaphylaxis after antigen challenge were investigated in rats after
      various drug treatments. The i.v. injection of ovalbumin (250 micrograms/kg) into
      actively sensitized rats induced marked thrombocytopenia and haemoconcentration
      within 5 min and significant leukocytosis within 30 min, lasting for 2 h after
      the challenge. Pretreatment with meclizine or terfenadine (15-30 mg/kg i.p.)
      inhibited antigen-induced haemoconcentration, whereas WEB 2086 (2-10 mg/kg i.p.)
      and PCA 4248 (5-10 mg/kg p.o.), two platelet-activating factor (PAF) antagonists,
      interfered with thrombocytopenia only. Azelastine (1-20 mg/kg p.o.) dose
      dependently inhibited antigen-induced haemoconcentration and thrombocytopenia but
      failed to block leukocytosis. Azelastine also inhibited the thrombocytopenia
      observed after the i.v. administration of PAF (4 micrograms/kg). Administration
      of ovalbumin at a dose of 1.5 mg/kg resulted in a lethal anaphylactic reaction in
      about 85% of the rats. Pretreatment with WEB 2086 (10 mg/kg i.p.), meclizine (30
      mg/kg i.p.) or both increased the survival rate from 15 to 57, 68 and 87%,
      respectively. Azelastine alone (20 mg/kg p.o.) completely blocked the lethal
      reaction. It was concluded that the ability of azelastine to antagonize histamine
      and PAF is important for its effectiveness against anaphylactic shock.

PMID- 1355733
TI  - Selectivity profile of the alpha 2-adrenoceptor antagonist efaroxan in relation
      to plasma glucose and insulin levels in the rat.
AB  - The effects of efaroxan (RX 821037A; 2-[2-(2-ethyl-2,3-dihydrobenzofuranyl)]-2
      imidazoline HCl) at alpha 1- and alpha 2-adrenoceptors were investigated in
      isolated tissues, pithed rats and conscious rats. In isolated tissues, efaroxan
      competitively antagonised the inhibitory effects of p-aminoclonidine in the
      electrically stimulated (0.1 Hz) rat vas deferens, (pA2 = 8.89) and the
      contractile effects of phenylephrine on the rat anococcygeus muscle (pA2 = 6.03).
      Efaroxan had a selectivity ratio (alpha 2/alpha 1) of 724 compared to a value of
      182 for idazoxan. In pithed rats, the i.v. doses of efaroxan (mumol/kg) producing
      2-fold shifts in dose-response curves for UK-14,304 at prejunctional cardiac
      alpha 2-adrenoceptors and postjunctional vascular alpha 2-adrenoceptors, and for
      cirazoline at postjunctional vascular alpha 1-adrenoceptors, were 0.05, 0.13 and
      2.96, respectively. In conscious fasted rats, prazosin (5 mg/kg p.o.) increased
      resting glucose levels and exacerbated the hyperglycaemic effects of UK-14,304
      and adrenaline. In contrast, efaroxan (1-5 mg/kg p.o.) had little effect on
      resting plasma glucose but markedly antagonised the hyperglycaemic actions of UK
      14,304 and adrenaline. Efaroxan increased resting plasma insulin levels and
      markedly potentiated the rise in insulin levels produced by adrenaline; this
      latter effect was prevented by the co-administration of propranolol. These
      results demonstrate that efaroxan is a potent and selective alpha 2-adrenoceptor
      antagonist and provide further support for the involvement of alpha 2
      adrenoceptors in glucose homeostasis.

PMID- 1355731
TI  - Effect of diets rich in medium-chain and long-chain triglycerides on lipogenic
      enzyme gene expression in liver and adipose tissue of the weaned rat.
AB  - The activity and mRNA concentrations of two lipogenic enzymes, fatty-acid
      synthase and acetyl-CoA carboxylase were measured in the liver and white adipose
      tissue of rats weaned to a carbohydrate-rich diet containing either long-chain or
      medium-chain fatty acids, and compared to those of rats weaned on a diet
      containing less than 1% (total energy) fat (high-carbohydrate diet). In the
      liver, the diet containing long-chain fatty acids inhibited the increase of both
      lipogenic-enzyme mRNA concentrations and activities seen at weaning on the high
      carbohydrate diet but did not prevent the decrease in phosphoenolpyruvate
      carboxykinase mRNA and activity. In contrast, the diet containing medium-chain
      fatty acids induced a slower but finally similar increase in lipogenic-enzyme
      mRNA concentrations and activities. In adipose tissue, a similar trend was
      observed, although the inhibitory effect of the diet containing long-chain fatty
      acids was considerably less marked than in liver. It is concluded that medium
      chain and long-chain fatty acids have not the same inhibitory potency of the gene
      expression of lipogenic enzymes, and that long-chain fatty acids have a more
      marked effect in the liver.

PMID- 1355734
TI  - Comparison of the effects of efaroxan and glibenclamide on plasma glucose and
      insulin levels in rats.
AB  - The effect of efaroxan (1 and 5 mg/kg p.o.; a selective alpha 2-adrenoceptor
      antagonist) was compared to glibenclamide (1 and 5 mg/kg p.o.; a standard
      sulphonylurea) on basal plasma glucose levels of fed and fasted rats. In
      addition, the effect of efaroxan (5 mg/kg p.o.) and glibenclamide (2 or 5 mg/kg
      p.o.), alone and in combination, on the hyperglycaemia and hyperinsulinaemia
      induced by glucose challenges, were investigated. An intra-arterial (250 mg/kg
      i.a.) and a subcutaneous (1 g/kg s.c.) glucose challenge were used to stimulate
      the fast and slow release phases of insulin secretion. Efaroxan increased plasma
      insulin levels in both conscious fed and fasted rats without greatly affecting
      plasma glucose levels. Glibenclamide also elevated insulin levels, but was
      associated with marked hypoglycaemia. Efaroxan and glibenclamide potentiated the
      slow and fast release of insulin secretion, but glibenclamide had a tendency to
      produce hypoglycaemia in these test situations, a property not shared by
      efaroxan. A combination of efaroxan and glibenclamide produced a greater
      elevation in the slow and fast insulin release phases than either compound alone,
      but did not enhance the hypoglycaemia seen with glibenclamide alone. These
      results provide further evidence that pancreatic alpha 2-adrenoceptors are
      involved in the regulation of insulin secretion.

PMID- 1355735
TI  - Pharmacological profiles of fentanyl analogs at mu, delta and kappa opiate
      receptors.
AB  - Receptor binding assays using [3H]DAGO ([D-Ala2,MePhe4-Gly5-ol]enkephalin) (mu),
      [3H]DPDPE ([D-Pen2,D-Pen5]enkephalin) (delta) and [3H]U-69593 (kappa) were done
      in guinea pig whole brain membranes. Agonist activity was determined in
      norbinaltorphimine or beta-funaltrexamine (beta-FNA) treated guinea pig ileum (mu
      and kappa, respectively) and beta-FNA-treated mouse vas deferens (delta). The
      compounds with highest affinity were the most potent at the mu-receptor. The
      selectivity observed in the binding affinities was also found in in vitro
      activity. No correlation was found between mu-affinity and selectivity; the
      highest affinity analog, lofentanil, was found to be among the least selective,
      while another high affinity analog, R30490, was the most mu-selective. The
      results show that not all fentanyls are highly mu-selective, and could produce
      actions through delta- and kappa-opiate receptors.

PMID- 1355736
TI  - Effects of dopamine receptor agonists on passive avoidance learning in mice:
      interaction of dopamine D1 and D2 receptors.
AB  - The present study examined the effects of dopamine D1 and D2 receptor agonists on
      the acquisition stage of passive avoidance learning and on locomotor activity in
      mice. The D2 agonist, RU 24213 (1-10 mg/kg s.c.), and the non-selective agonist,
      apomorphine (0.3-3 mg/kg s.c.), but not the D1 agonist, SKF 38393 (1-10 mg/kg
      s.c.), impaired learning and activated locomotion. RU 24213 (1 mg/kg s.c.) was
      more effective in impairing learning than in activating locomotion. The
      concurrent administration of SKF 38393 (10 mg/kg i.p.) and RU 24213 (1 and 3
      mg/kg s.c.) produced a synergistic effect in both behavioral situations. The D1
      antagonist, SCH 23390 (0.025 mg/kg i.p.), slightly inhibited the effects of
      apomorphine and of the combination of SKF 38393 and RU 24213 on learning but not
      on locomotion. The D2 antagonist, (-)-sulpiride (40 mg/kg i.p.), completely
      blocked these effects in both situations. These results suggest that dopamine
      receptor agonists impair passive avoidance learning through the D2 receptor, and
      that D1 and D2 receptors act synergistically in this impairment, as they do in
      their effects on locomotion. The involvement of D1 and D2 receptors is
      qualitatively similar in each of these behaviors, although some small differences
      may exist.

PMID- 1355737
TI  - Partial and full dopamine D1 receptor agonists in mice and rats: relation between
      behavioural effects and stimulation of adenylate cyclase activity in vitro.
AB  - The dopamine (DA) D1 agonists, SK&F 83959, SK&F 75670, SK&F 38993, SK&F 81297 and
      SK&F 80723, had variable abilities to stimulate adenylate cyclase activity in rat
      striatal homogenates. Their efficacies, in relation to the effect of 100 microM
      DA were 0, 33, 69, 68 and 81%, respectively. In rats, all compounds induced (1)
      contralateral circling behaviour after unilateral 6-hydroxy-DA lesions, (2)
      ipsilateral circling behaviour after midbrain hemitransection after cotreatment
      with the D2 agonist quinpirole and (3) oral stereotypies after their combination
      with quinpirole. Maximum effects and rank order of potencies were similar in the
      three test models. In mice SK&F 83959, SK&F 75670 and SK&F 38393 inhibited
      methylphenidate-induced gnawing behaviour and induced no or only weak
      hypermotility. SK&F 81297 induced marked hypermotility which was partially
      inhibited by SK&F 83959 and SK&F 75670 and was completely blocked by the D1
      antagonist, SCH 23390. It is concluded that no relation could be demonstrated
      between the efficacy to stimulate adenylate cyclase and to induce circling
      behaviours and stereotypies in rats. In contrast, a relation between biochemical
      and behavioural efficacies was found in the mouse models. The results suggest
      that different subtypes of D1 receptors mediate the behavioural effects reported
      in this study.

PMID- 1355738
TI  - Competitive and non-competitive NMDA receptor antagonists in spatial learning
      tasks.
AB  - The effects of the competitive N-methyl-D-aspartate (NMDA) receptor antagonists,
      CGP37849 (3 or 6 mg/kg i.p.) and its ethyl ester CGP39551 (5 or 15 mg/kg i.p.)
      and of the non-competitive NMDA receptor antagonist, dizocilpine (0.16 mg/kg;
      i.p.) on acquisition by rats of different spatial orientation tasks in an 8-arm
      radial maze were evaluated. Neither of the CGP compounds influenced locomotor
      activity during spontaneous alternation, only dizocilpine increased the number of
      arm entries (locomotion). Preferred angles between consecutive arm entries were
      changed by the high doses of CGP37849 (6 mg/kg), CGP39551 (15 mg/kg) and
      dizocilpine (0.16 mg/kg). The high doses of both CGP compounds as well as
      dizocilpine produced impairments in the acquisition of an egocentric orientation
      task and an allocentric reversal task indicated by an increased number of arm
      entries and re-entries. Such amnesic effects did not occur after administration
      of low doses of CGP37849 (3 mg/kg) and CGP39551 (5 mg/kg), doses which are
      sufficient to produce anticonvulsant and anticataleptic effects. In contrast, the
      non-competitive NMDA receptor antagonist, dizocilpine, produced amnesic effects
      over the entire behaviourally effective dose range.

PMID- 1355739
TI  - Does rilmenidine act in vivo on central alpha 2-adrenoceptors modulating
      noradrenaline release?
AB  - Noradrenaline release evoked by electrical stimulation was recorded in the rat
      hypothalamus by in vivo electrochemistry. Rilmenidine (0.3-10 mg kg-1 i.v.) did
      not diminish this evoked release while clonidine induced a dose-dependent
      decrease. These results further suggest that the antihypertensive action of
      rilmenidine is not mediated by central alpha 2-adrenoceptors and might explain
      why, unlike clonidine, rilmenidine does not have sedative effects.

PMID- 1355740
TI  - Pharmacological and mechanical heterogeneity of cat isolated ophthalmociliary
      artery.
AB  - The mechanical, histological and pharmacological properties of the isolated cat
      ophthalmociliary artery are reported and compared for passively stretched ring
      segments from three locations on the artery. Ring segments were mounted in a
      modified myograph system after the method of Hogestatt, Andersson and Edvinsson
      (1983, Acta Physiol Scand. 117, 49-61) and comparative length tension curves were
      measured. The most distal segment (DOA), nearest the eye, developed by far the
      smallest maximal tension compared to the middle segment (MOA) and the most
      proximal segment (POA), despite the fact that lumen diameters were similar. All
      segments displayed a phasic and tonic component in response to passive stretching
      and during activation with K(+)-Krebs. Cumulative contractile dose-response
      curves were measured for nine agonists: histamine (HIS), 5-hydroxytryptamine (5
      HT), dopamine (DOPA), adrenaline (A), noradrenaline (NA), tyramine (TYR),
      phenylephrine (PHE), isoproterenol (ISOP) and xylazine (XYL) and the maximum
      active tension developed at a concentration of 10(-3) M was compared with that
      for 0.124 M K(+)-Krebs. The order of contraction magnitude in the three segments
      was: POA, HIS much greater than Kmax much greater than NA greater than A greater
      than DOPA greater than PH = TYR greater than 5-HT = ISOP greater than XYL; MOA,
      Kmax much greater than NA much greater than A = HIS much greater than DOPA
      greater than ISOP = PHE greater than TYR = 5-HT greater than XYL; DOA, Kmax much
      greater than NA greater than A greater than HIS = DOPA greater than ISOP greater
      than PHE = 5-HT greater than XYL = TYR. Pre-activation did not produce relaxation
      in response to histamine and isoproterenol. Testing with specific alpha 1 and
      beta antagonists supported the presence of alpha 1 receptors but not beta
      receptors. It is concluded that functional HIS, alpha 1 and 5-HT receptors are
      present and that the ophthalmociliary artery is heterogeneous in its response to
      HIS, with the POA segment producing the largest responses. The magnitude of the
      contractile responses to A and NA grew with increasing passive tension, whereas
      the response to histamine was independent of passive tension.

PMID- 1355741
TI  - Reconstitution of the photoreceptor-pigment epithelium interface: L-glutamate
      stimulation of adhesive interactions and rod disc shedding after recombination of
      dissociated Xenopus laevis eyecups.
AB  - In order to investigate adhesive interactions between photoreceptor and pigment
      epithelial cells, we have mechanically separated neural retinas from Xenopus
      laevis eyecups and then recombined the tissues in vitro. When tissue pairs are
      incubated in a defined medium, cell-cell contact is achieved within 3 hr.
      However, the average proportion of reassembled eyecups in which photoreceptor
      outer segments interdigitate with epithelial microvilli is limited. Furthermore,
      rod disc shedding does not take place in these cultures, even following a dark to
      light transition. When recombined tissues are placed in medium supplemented with
      12 mM L-glutamate, retinal reattachment is enhanced and there is a four-fold
      increase in epithelial phagosome content. The positive effect of excitatory amino
      acid exposure on shedding, however, is restricted to regions where visual and
      epithelial cells interdigitate. These results indicate that re-establishment of
      cell contact may be necessary for shedding of apical disc membranes prior to
      their engulfment by the epithelium. While reattachment is not affected by pre
      incubation of separated tissues in normal medium, rod photoreceptors fail to
      undergo membrane turnover in response to L-glutamate if a delay of 1 hr or more
      is interposed between isolation of the retina and its recombination with the
      pigment epithelium. This is probably due to a decline in retinal function in
      culture, since a similar preincubation of the pigment epithelium prior to
      reassembly with a freshly isolated retina does not inhibit the shedding
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355742
TI  - Postnatal X-ray irradiation effects on glomerular layer of rat olfactory bulb:
      quantitative and immunocytochemical analysis.
AB  - In the rat olfactory bulb, the majority of interneurons in the glomerular layer
      (GL) are supposed to be generated during first postnatal week. Low and repeated
      doses of X-rays (200 rad x 4 and 200 rad x 6) were used during this period to
      impair the development of interneurons. The resulting effects of olfactory bulb
      neurons were examined stereologically and immunocytochemically in animals of 4
      and 12 weeks of age. Quantitative analysis showed that, 1) the volume of the GL
      decreased to 55% (1200 rad) - 70% (800 rad) of control, 2) numerical cell
      densities in GL decreased to 40% (1200 rad) - 60% (800 rad) of control, thus
      resulting in 3) a decrease of the total cell number in GL to 20% (1200 rad) - 40%
      (800 rad) of control in irradiated olfactory bulbs of animals 4 weeks old. In
      comparison, mitral cells, which are generated prenatally, were much less affected
      (total cell number: 70-80% of control), indicating a selective loss of cells
      generated during the first postnatal week in GL. Effects on somata and processes
      immunoreactive for GABA, tyrosine hydroxylase (TH), calbindin D-28K and
      parvalbumin (PV) were examined in irradiated bulbs of both 4 and 12 week-old
      rats. All of these immunoreactive elements showed a drastic decrease in all
      layers. Semiquantitative analysis showed that in the GL, calbindin D-28K
      immunoreactive (calbindin D-28K(+)) neurons decreased more extensively than TH
      immunoreactive (TH(+)) and GABA-like immunoreactive (GABA(+)) neurons; that is,
      TH(+) and GABA(+) neurons decreased to 20% (1200 rad) - 40% (800 rad) of control,
      whereas calbindin D-28K(+) neurons decreased to 10% (1200 rad) - 30% (800 rad) of
      control in the GL of irradiated bulbs. These findings indicated that larger
      proportions of calbindin D-28K(+) neurons might be generated during the first
      postnatal week than those of GABA(+) and TH(+) neurons. Furthermore, in
      irradiated bulbs the proportion of GABA(-)TH(+) cells in TH(+) cells increased to
      about twice of control, and the estimated total numbers of GABA(-)TH(+) cells in
      irradiated rats were 95% (800 rad) and 40% (1200 rad) of control. These
      observations suggest that the majority of GABA(-)TH(+) neurons were less affected
      by X-ray irradiation during the first postnatal week and thus that they might be
      generated in the prenatal period. Since during the first 2 postnatal weeks,
      neurons showing GABA(-)TH(+) were not seen in GL (Kosaka et al. 1987a), the
      majority of GABA(-)TH(+) neurons in adult olfactory bulb were assumed to change
      their phenotype at some postnatal developmental period.

PMID- 1355743
TI  - MPTP induced hemiparkinsonism in monkeys: behavioral, mechanographic,
      electromyographic and immunohistochemical studies.
AB  - A single infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) into
      the right internal carotid artery of Macaca mulatta monkeys resulted in akinesia
      and rigidity of the contralateral limb. The immunohistochemical study revealed a
      dramatic reduction in the number of TH-immunoreactive cells in the substantia
      nigra of the infused side (70-81%). After unilateral MPTP-treatment movement
      parameters and EMG activity were altered; the agonist muscle developed increased
      EMG activity associated with a shift of antagonist muscle activity. These results
      confirm that hemiparkinsonian monkeys are a valuable model of parkinsonism which
      can be useful in studies of movement disorder physiology and therapy of
      Parkinson's disease.

PMID- 1355745
TI  - An evaluation of the antihistamine activity of acrivastine and its onset in human
      skin.
AB  - In a double-blind, two-period crossover study, 24 healthy volunteers were
      evaluated to establish the time of onset of action of activity of acrivastine in
      suppressing the weal and flare response to intradermally injected histamine.
      Volunteers received single doses of 8 mg acrivastine and placebo according to a
      fully randomized, balanced treatment plan. Acrivastine significantly (P less than
      0.002) reduced the flare response induced by 0.4 micrograms histamine challenge
      15 min after oral acrivastine dosing when compared with placebo. A significant (P
      less than 0.001) reduction of the weal response was noted at 25 min, although
      trends in this direction were already present at earlier time points.

PMID- 1355744
TI  - Cryopreservation, survival and function of intrastriatal fetal mesencephalic
      grafts in a rat model of Parkinson's disease.
AB  - In the present study we quantitatively assessed to what extent freeze-storage at
      liquid nitrogen temperature influences the survival and function of fetal
      mesencephalic grafts in the dopamine-depleted rat striatum. Ventral mesencephalic
      (VM) tissue was dissected from rat fetuses and stored overnight in a preservative
      medium at 4 degrees C (hibernation). It was grafted intrastriatally either as a
      fresh cell suspension or was frozen as tissue fragments or as a cell suspension
      after stepwise incubation in ascending concentrations of dimethyl-sulphoxide.
      Following a cryopreservation interval of 80 days in liquid nitrogen, the frozen
      samples were rapidly thawed, rinsed, and grafted. Cellular viabilities of graft
      cell suspensions, as assessed by ethidium bromide/acridine orange staining, were
      decreased from 90% in fresh tissue to 38-35% in frozen and thawed tissue.
      Amphetamine-induced turning behavior at 6 weeks post-grafting was significantly
      attenuated in hosts that had received fresh grafts or grafts that were frozen as
      tissue fragments. Tyrosine hydroxylase-(TH-) immunocytochemistry of recipient
      brains revealed significant decreases in TH-positive graft cell numbers in rats
      grafted with cryopreserved tissue (38-42% of fresh tissue). Moreover, the dye
      exclusion viability of thawed VM tissue was found to accurately predict the
      subsequent graft survival. There was no difference with respect to graft cell
      numbers between the two freezing methods employed, though block storage seems to
      be more simple from a practical point of view.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355746
TI  - Lansoprazole and omeprazole have similar effects on plasma gastrin levels,
      enterochromaffin-like cells, gastrin cells and somatostatin cells in the rat
      stomach.
AB  - This study compares the effects of lansoprazole and omeprazole on the activation
      and proliferation of enterochromaffin-like (ECL) cells in the rat stomach.
      Lansoprazole was given orally once daily for 10 weeks in two doses, 135 and 200
      mumol/kg. Omeprazole was given by the same regimen in a dose of 400 mumol/kg,
      which is equipotent in terms of acid inhibition to the higher lansoprazole dose.
      Lansoprazole (both doses) as well as omeprazole raised the plasma gastrin levels
      about 11-fold 2 h after dosing and 8-to 10-fold 24 h after dosing, reflecting
      complete (2 h) and 70-80% (24 h) reductions of gastric acid secretion.
      Administration of either drug for 10 weeks increased the weight of the stomach
      and the oxyntic mucosa. The oxyntic mucosal histidine decarboxylase activity,
      histamine concentration and ECL cell density were increased to the same extent in
      the rats given either of the two lansoprazole doses or omeprazole. The numbers of
      antral gastrin cells were doubled and the numbers of antral somatostatin cells
      half that in the controls. These results show that long-standing lansoprazole
      evoked hypergastrinemia affects the ECL cell similarly to omeprazole, ranitidine
      and other acid secretion inhibitors.

PMID- 1355748
TI  - Comparison of Bacillus thuringiensis subsp. israelensis CryIVA and CryIVB cloned
      toxins reveals synergism in vivo.
AB  - When the gene for the mosquitocidal protein CryIVA was expressed in two strains
      of Bacillus thuringiensis (Bt) cured of their resident delta-endotoxin genes, the
      protein accumulated as large inclusions. The inclusions produced in the Bt subsp.
      kurstaki recipient strain were twice as soluble at alkaline pH as the inclusions
      produced in Bt subsp. israelensis. Solubilized protoxins were activated by
      treatment with mosquito gut extracts or trypsin for varying lengths of time and
      tested for in vitro cytotoxicity on cell lines of three genera of mosquito.
      CryIVA treated with any of the mosquito gut extracts for 6 h showed significant
      toxicity against Anopheles gambiae cells and slight activity on Culex
      quinquefasciatus cells. For CryIVB, the only significant cytotoxicity observed
      was against Aedes aegypti cells after treatment with Aedes gut extract. In in
      vivo bioassays, both CryIVA, purified from either of the Bt recipient strains,
      and CryIVB inclusions were similarly toxic to A. aegypti and A. gambiae larvae
      but CryIVA was 25-fold more toxic to C. quinquefasciatus. Synergism in vivo
      between the two toxins was revealed when results from assaying single toxins and
      mixtures were compared. Mixtures of CryIVA and CryIVB proved to be 5-fold more
      toxic to Culex than either toxin used singly and showed a reduced but similar
      synergism when tested against Aedes and Anopheles larvae. The synergism was not
      duplicated in vitro using cell lines from these three insects.

PMID- 1355747
TI  - Comparison between HLA-DRB and DQ DNA sequences and classic serological markers
      as type 1 (insulin-dependent) diabetes mellitus predictive risk markers in the
      Spanish population.
AB  - The question of HLA susceptibility to Type 1 (insulin-dependent) diabetes
      mellitus remains unresolved. In the present study, 127 diabetic patients and 177
      unrelated control subjects have been analysed for their class I and class II
      serological antigens, class II (DR, DQ) DNA restriction fragment length
      polymorphisms and DQA1 and B1 exon-2 nucleotide sequences and their corresponding
      amino acid residues. By using the aetiologic fraction (delta) as an almost
      absolute measure of the strongest linkage disequilibrium of an HLA marker to the
      putative Type 1 diabetes susceptibility locus, it has been found that the
      strength of association of the HLA markers may be quantified as follows: DR4 less
      than DR3 less than DR3 or DR4 less than non-Aspartate 57 beta DQ and Arginine 52
      alpha DQ less than Arginine 52 alpha DQ. Thus, molecular HLA-DQ markers appear to
      be more accurate as susceptibility markers than the classic serologically defined
      ones (DR3 and DR4); however, any effect of DQ markers disappears when non-DR3/DR4
      individuals are considered, suggesting that DR factors (or others in between DQ
      and DR) are also important. In addition, a dominant non-Aspartate 57 beta DQ
      susceptibility theory does not hold (but a recessive one does) in our diabetic
      population (probably due to the high frequency of the protective DR7-non
      Aspartate 57 beta DQ haplotypes); Arginine 52 alpha DQ is the best single HLA
      marker found in our population, both as a recessive or as a dominant one. Also
      there are 13 patients in our sample who bear neither Arginine 52 alpha DQ nor non
      Aspartate 57 beta DQ susceptibility factors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1355749
TI  - Underrecognition of tardive dyskinesia and drug-induced parkinsonism by
      psychiatric residents.
AB  - Recognition of tardive dyskinesia (TD) and other neuroleptic, drug-induced,
      extrapyramidal side effects presents a major challenge in modern clinical
      psychopharmacology. Failure to recognize these disorders can lead to poor patient
      care and may contribute to societal pressure for external control of psychiatric
      practice. This study reports the occurrence of tardive dyskinesia and drug
      induced parkinsonism (DIP) in 101 inpatients, and documents underrecognition of
      both disorders by resident physicians. Researchers noted TD in 28% of cases and
      residents only described TD (or symptoms of TD) in 12%. The researcher determined
      DIP prevalence rate of 26% contrasted with an 11% rate found by residents.
      Patients with psychotic disorders were more likely than other patients to have
      researcher-identified TD, whereas DIP (researcher cases) occurred more often in
      patients with affective diagnoses. Residents tended to miss milder cases of TD,
      and to miss DIP in younger patients and in patients with affective disorders.
      Improved teaching and clinical exams are recommended to improve recognition.

PMID- 1355750
TI  - The suppressor of forked locus in Drosophila melanogaster: genetic and molecular
      analyses.
AB  - The suppressor of forked, su(f) locus is one of a class of loci in Drosophila
      whose mutant alleles are trans-acting allele-specific modifiers of transposable
      element-insertion mutations at other loci. Mutations of su(f) suppress gypsy
      insert alleles of forked and enhance the copia insert allele white apricot. Our
      investigations of su(f) include genetic and molecular analyses of 19 alleles to
      determine the numbers and types of genetic functions present at the locus. Our
      results suggest the su(f) locus contains multiple genetic functions. There are
      two distinct modifier functions and two vital functions. One modifier function is
      specific for enhancement and the other for suppression. One vital function is
      required for normal ecdysterone production in the third larval instar, the other
      is not. We present a restriction map of the su(f) genomic region and the results
      of an RFLP analysis of several su(f) alleles.

PMID- 1355752
TI  - [The basic-opioid Tramal report from the symposium "Retrospect and perspectives
      in pain relief-15 years experience with Tramal". 41st German Physicians"
      Congress. Berlin, 11 June 1992].

PMID- 1355753
TI  - [Three-country symposium on biologic psychiatry. Lausanne, 3-5 September 1992.
      Abstracts].

PMID- 1355751
TI  - Intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated
      antigen-1 (LFA-1) expression in human epiretinal membranes.
AB  - Various histogenetically different cell types such as macrophages, retinal
      pigment epithelial cells, glial cells, and fibroblasts are involved in the
      formation of epiretinal membranes. In the development of such multicellular
      tissues, cellular adhesion molecules (CAMs) are necessary for cell migration,
      proliferation, and localization, and the transfer of information between the
      cells. We investigated the expression of the intercellular adhesion molecule 1
      (ICAM-1) and the leukocyte function-associated antigen 1 (LFA-1) in frozen
      sections of epiretinal membranes in proliferative vitreoretinopathy (PVR),
      proliferative diabetic retinopathy (PDR), macular pucker, and recurrent membranes
      after intraocular silicone oil tamponade using the indirect immunoperoxidase
      method. ICAM-1 forms a receptor-ligand pair with LFA-1 and is involved in a
      number of significant cellular interactions, e.g. in providing dynamic position
      specific information to guide lymphocyte and leukocyte localization in the immune
      response. ICAM-1 is a member of the immunoglobulin gene super-family of CAMs. LFA
      1 is a member of the integrin family of cell membrane receptors. It mediates a
      wide range of lymphocyte, monocyte, natural killer cell, and granulocyte
      interactions with other cells in immunity and inflammation, and it is a receptor
      for ICAM-1. The LFA-1 interaction with its ligand ICAM-1 mediates not only cell
      adhesion but also signal transduction in immunologic and inflammatory cell
      responses. Basal ICAM-1 expression is normally low on nonhematopoietic cells, but
      it can be subject to an up-and-down regulation by various cytokines.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1355754
TI  - Antihistaminic activity of quinethindole: a 2-substituted pyrazinopyridoindole
      derivative.
AB  - Quinethindole, a 2-substituted pyrazinopyridoindole, showed specific
      antihistaminic (H1) activity in various in vivo and in vitro test models. It also
      inhibited antigen-induced contraction of ileum of sensitized guinea pig. The
      antihistaminic activity was of competitive nature.

PMID- 1355755
TI  - Expression of HER-2/neu in renal-cell carcinoma. Correlation with histologic
      subtypes and differentiation.
AB  - Twenty-four renal-cell carcinomas (RCC) and corresponding non-neoplastic kidney
      tissue were examined for amplification and expression of the HER-2/neu gene. Gene
      amplification was examined by slot-blot analysis, mRNA expression by in situ
      hybridization and Northern blot analysis, and protein expression by
      immunohistochemistry. Northern-blot analysis revealed lower expression of HER
      2/neu mRNA in clear-cell (p less than 0.001) and compact (p less than 0.001)
      tumor subtypes, while chromophilic, chromophobic and tubulo-papillary subtypes
      did not show significant differences in HER-2/neu gene expression, as compared
      with non-neoplastic kidney tissues. HER-2/neu gene expression was not
      significantly associated with tumor stage. Low differentiation (G3) was
      associated with lower HER-2/neu gene expression, but the number of G3 cases was
      too small for statistical analysis. HER-2/neu gene amplification was not found in
      any of the tumors. The results of in situ hybridization and immunohistochemistry
      generally agreed with those of Northern-blot analysis. We conclude that HER-2/neu
      gene expression correlates with Thoenes' classification of RCC and may be
      inversely related to tumor differentiation; it is probably not involved in
      progression of RCC, in contrast to carcinomas of other locations (e.g. breast,
      ovary).

PMID- 1355756
TI  - Over-expression of P-glycoprotein and glutathione S-transferase pi in MCF-7 cells
      selected for vincristine resistance in vitro.
AB  - This study has provided evidence that exposure of the wild-type MCF-7 human
      breast carcinoma cell line to the mutagen ethyl methane sulphonate (EMS),
      followed by selection in vincristine (VCR), resulted in a stably-resistant
      subline, designated VCREMS, which expressed an approximately 14-fold level of
      resistance to VCR. This VCREMS subline showed cross-resistance (3-fold) to
      adriamycin (ADR) and to etoposide (3-fold), but not to cisplatin. The addition of
      a non-toxic concentration of verapamil (6.6 microM) significantly enhanced VCR
      cytotoxicity only in the resistant subline. This resistance was associated with
      over-expression of P-glycoprotein (Pgp), but without a concomitant increase in
      Pgp mRNA or gene amplification. In addition, activities of total glutathione S
      transferases (GST) and glutathione peroxidase were elevated in this resistant
      subline, with over-expression of the GST-pi isozyme and its associated mRNA being
      identified, without gene amplification. This VCR-selected resistant MCF-7 cell
      line therefore provides another example of a breast carcinoma subline in which
      there is co-ordinate over-expression of both Pgp and GST-pi, without attributing
      a causal relationship to either event, and extends the range of anti-tumour drugs
      known to elicit modifications in glutathione metabolism.

PMID- 1355758
TI  - Epidermal growth factor reduces HER-2 protein level in human ovarian carcinoma
      cells.
AB  - Over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian,
      endometrial, and mammary carcinoma is an indicator of poor prognosis.
      Interactions between the epidermal growth factor (EGF) receptor and the HER-2
      protein have been described. The aim of this study was to elucidate the effects
      of EGF on HER-2 expression. In the human ovarian carcinoma cell lines HTB-77,
      OVCAR-3, 2780, SKOV-6, SKOV-8 and 2774, and the human mammary tumor cell line
      SKBR-3, total cellular p185HER-2 was determined by an ELISA, whereas the surface
      p185HER-2 was measured with a living-cell RIA. Stimulation of these cell lines
      with either EGF (0.1-30 nM) or TGF-alpha (0.1-30 nM) led to a significant
      reduction in p185HER-2 expression. The effect was more pronounced in cells with
      normal HER-2 expression. A reduction of mRNA levels for p185HER-2 by EGF was
      observed in OVCAR-3 cells but not in the over-expressing lines HTB-77 and SKBR-3.
      Interestingly, the EGF-induced effect was not always associated with growth
      stimulation and was not correlated with the number of EGF binding sites detected
      by a radioligand assay. Our data indicate that EGF treatment results in a down
      regulation of p185HER-2.

PMID- 1355757
TI  - Two new human cholangiocarcinoma cell lines and their cytogenetics and responses
      to growth factors, hormones, cytokines or immunologic effector cells.
AB  - Two new human cholangiocarcinoma (CC) cell lines (CC-SW-I and CC-LP-I) were
      established and maintained in culture for 2 years. Histologically, both original
      liver tumors were adenocarcinomas, and the cell lines exhibited morphologic
      features of moderately differentiated adenocarcinoma. Immunohistochemistry showed
      that both cell lines were strongly positive for cytokeratin AEI but negative for
      carbohydrate tumor-associated antigen, CA19-9. Ultrastructural analysis of both
      cell lines showed the presence of tight junctional complexes and focally formed
      microvilli. Both CC cell lines were tumorigenic in nude mice. Cytogenetic
      analysis showed that both cell lines expressed highly aneuploid karyotypes with
      numerous structural and numerical deviations. CC-SW-I was hypodiploid with
      numerous chromosome losses and structural rearrangements, while CC-LP-I was
      hyperdiploid and displayed multiple additional chromosomes. Doubling times for
      the CC-SW-I and CC-LP-I cell lines in the presence of 15% fetal bovine serum were
      72 hr and 180 hr, respectively. Growth of the CC-SW-I cell line was significantly
      stimulated in the presence of insulin, while that of the CC-LP-I cell line was
      significantly augmented by epidermal growth factor (EGF). In contrast,
      dexamethasone strongly inhibited proliferation of both cell lines in a dose
      dependent manner. Among various recombinant cytokines examined for effects on
      growth or surface antigen expression on CC cell lines, only interleukin I-beta
      (ILI-beta) strongly inhibited growth of the CC-LP-I cell line, while interferons
      (IFNs) or tumor necrosis factor-alpha (TNF-alpha) were mildly inhibitory. Both
      tumor cell lines were resistant to natural killer (NK) cells but sensitive to
      lymphokine-activated killer (LAK) cells. Preincubation of tumor cells with IFN
      gamma, IFN-alpha or TNF-alpha significantly decreased the susceptibility of each
      tumor cell line to lysis by LAK cells, and the change in sensitivity did not
      correlate with the expression of HLA antigens or intercellular adhesion molecule
      I (ICAM-I) on the surface of tumor cells. These 2 CC cell lines are expected to
      provide valuable information about cell biology of human CC.

PMID- 1355759
TI  - Nonsurgical management of minimal and moderate endometriosis to enhance
      fertility.

PMID- 1355760
TI  - Ovarian pregnancy in polycystic ovary syndrome: a case report.
AB  - A case is reported of ectopic pregnancy occurring within an ovary with the
      morphologic appearance of polycystic ovary syndrome (PCOS). The hyperandrogenism
      and elevated LH/FSH ratio characteristic of PCOS were noted 2 months after
      removal of the ovarian gestation. The thickened ovarian cortex of the PCOS ovary
      and a defect in oocyte-cumulus complex detachment within the follicle are
      suggested as possible factors contributing to intraovarian fertilization in PCOS.

PMID- 1355761
TI  - Ectopic pregnancy, the new gynecological epidemic disease: review of the modern
      work-up and the nonsurgical treatment option.
AB  - Over the past few decades, the incidence of ectopic pregnancy has increased
      almost to the extent of an "epidemic disease." Early diagnosis of tubal
      pregnancy, with the aid of serum human chorionic gonadotropin, high-resolution
      ultrasound, and the more liberal use of laparoscopy, has dramatically reduced
      both maternal mortality and the need for radical surgery. Despite this, women
      with previous ectopic pregnancies still have reduced fertility potential. We
      report on some current aspects of the epidemiology, etiology, and work-up of
      ectopic pregnancy. In a review of 328 patients, gleaned from the literature, who
      were treated with various nonsurgical options, 283 (86%) were able to avoid
      surgery. The benefits, safety, and efficacy of the various treatment options are
      discussed, with appropriate recommendations for their use.

PMID- 1355762
TI  - Evidence that difference in size of fraternal twins may originate during early
      gestation: a case report.
AB  - We describe a woman who conceived by in vitro fertilization (IVF) and embryo
      transfer (ET). Transvaginal ultrasound demonstrated at least 1 week's difference
      in size of twin gestations from 1 month post-transfer of embryos to delivery.
      Differences in sac size, crown-rump length, and gestational growth are discussed,
      as are implications of ultrasound in early pregnancy.

PMID- 1355763
TI  - Incidence of congenital uterine anomalies in repeated reproductive wastage and
      prognosis for pregnancy after metroplasty.
AB  - To discover the exact incidence of congenital uterine anomalies among infertile
      patients, hysterosalpingography was performed on 1,200 married women with a
      history of repeated reproductive wastage. Out of 1,200 hysterosalpingographies,
      188 revealed congenital uterine anomaly (15.7%). The degree of uterine cavity
      deformity in the anomalies was evaluated during hysterosalpingography using the
      X/M ratio. This indicated that the incidence of repeated spontaneous abortion in
      cases with low-grade anomalies is as high as the incidence among cases with more
      severe anomalies. A significant improvement in maintaining pregnancy was observed
      after metroplasty; more than 84% of postoperative pregnancies were successfully
      maintained, whereas none of the 233 presurgical pregnancies had lasted full term.
      As a control group, 47 other women with anomalies were randomly chosen, and their
      subsequent pregnancies were monitored, without metroplasty. Of their pregnancies,
      94.4% terminated spontaneously before 12 weeks of gestation.

PMID- 1355764
TI  - Androgen response in polycystic ovarian syndrome to FSH treatment after LHRH
      agonist suppression.
AB  - Anovulatory patients with clomiphene-resistant polycystic ovarian syndrome were
      treated by two different stimulation protocols. Follicular maturation was induced
      in 14 women with hMG; 12 of them received pure FSH in a later series after
      previous pituitary desensitization with the LHRH agonist D-Trp-6-LHRH
      (Decapeptyl). Both basal and stimulated serum androstenedione, testosterone, and
      free testosterone were elevated in the hMG-treated group compared with controls.
      However, only androstenedione exhibited a significant increase between early and
      late follicular levels. Marked suppression of these androgens has been observed
      after two weeks of LHRH agonist pretreatment, but nearly the same concentrations
      were obtained with pure FSH on the day of hCG administration. Again, only the
      increase of androstenedione levels proved to be significant. Polycystic
      follicular maturation, hyperstimulation, and peak estradiol levels were
      comparable with the two protocols. Nevertheless, more pregnancies were achieved
      using the LHRH agonist+FSH combination (4 vs. 1). It is suggested that 2 weeks'
      suppression of ovarian androgens with LHRH agonist is not sufficient to
      neutralize the unfavourable intraovarian mechanisms interfering with normal
      folliculogenesis. More data are required to confirm the superiority of LHRH
      agonist pretreatment in the management of polycystic ovarian syndrome.

PMID- 1355765
TI  - Reference period analysis of vaginal bleeding with triphasic oral contraceptive
      agents containing norethindrone or levonorgestrel: a comparison study.
AB  - The World Health Organization recommends the use of fixed reference periods for
      quantification of the incidence and severity of vaginal bleeding when patients
      use various forms of contraception. Ninety- and 110-day reference periods were
      used in the analysis of data from daily menstrual diaries kept by 72 healthy
      women in a one-year study of oral contraceptive agents containing ethinyl
      estradiol and either norethindrone or levonorgestrel. Analysis of bleeding
      patterns reported during both 90-day and 110-day periods revealed fewer days of
      bleeding and/or spotting overall with norethindrone than with levonorgestrel
      (e.g., a mean of 16.06 vs. 19.55 days, respectively, over the first 90-day
      period; P = .013) and significantly shorter bleeding and/or spotting episodes
      with the norethindrone preparation. This trend persisted when data were adjusted
      for a day-1 pill start. Using either method of analysis, duration of bleeding
      episodes was shorter among subjects taking norethindrone than levonorgestrel.
      Pills were missed in both study groups, but more women in the LNG/EE group missed
      from 1 to 3 pills in at least one cycle (31 vs. 21 in the NET/EE group). The
      between-group difference in bleeding events may be due to intrinsic hormonal
      differences in regimens or to the greater number of pills missed among
      levonorgestrel users.

PMID- 1355766
TI  - Teratological evaluation of an injectable male antifertility agent, styrene
      maleic anhydride, in rats.
AB  - Polymer styrene Maleic anhydride (SMA) dissolved in dimethylsulphoxide (DMSO) was
      injected into the lumen in each vas deferens of male rats at dose levels of 0.25
      mg, 0.50 mg, 1.0 mg, 2.5 mg, and 5.0 mg, while control rats (groups 1) received
      0.03 mL DMSO in each vas deferens. After 4 weeks, the lumen was flushed with 0.1
      mL DMSO and the animals were left for another 6 weeks to regain fertility. These
      rats were mated with virgin and coeval females. No anomaly was observed which
      could be related to teratogenic action of the polymer in pregnant mothers or
      fetuses.

PMID- 1355767
TI  - Dexamethasone selectively regulates the activity of enzymatic markers of cerebral
      endothelial cell lines.
AB  - Two endothelial cell lines were derived from grafts of the central nervous system
      using retrovirus mediated gene transfer to introduce the polyoma middle-T
      oncogene into fetal rat brain endothelial cells and transplantation of these
      cells into adult rat brain. In this report, we further characterize these cells
      and the effect of dexamethasone on the expression of specific enzymatic markers.
      These cells take up acetylated low density lipoprotein, leucine, and glucose, and
      express Factor VIII-related antigen, angiotensin converting enzyme, alkaline
      phosphatase, gamma-glutamyltranspeptidase, and as yet undescribed aminopeptidase
      A and B-like enzymes. When grown on semi-permeable membranes, these transformed
      cells do not spontaneously retain small hydrophilic molecules. In culture, one of
      the lines (EC 193) forms a confluent monolayer of spindle-shaped cells
      homogenously expressing gamma-glutamyltranspeptidase at a level comparable to
      primary cells. The other cell line (EC 219) grows as clusters of elongated cells,
      and gamma-glutamyltranspeptidase activity is expressed mainly in cells forming
      the clusters. This clustered pattern changes to a confluent one after culture on
      type-I collagen. Dexamethasone increases angiotensin-converting enzyme activity,
      and decreases the expression of gamma-glutamyltranspeptidase and aminopeptidase
      A, whereas the aminopeptidase B activity is little modified. Inhibition of
      aminopeptidase A activity by amastatin, potentiates angiotensin II effects on DNA
      synthesis. These results indicate that retrovirally transformed brain endothelial
      cells are a useful model for studying the blood-brain barrier in vitro and that
      dexamethasone, an agent with the potential to reduce brain edema, directly
      affects some blood-brain barrier properties in these endothelial cell lines.

PMID- 1355768
TI  - Identification of the Escherichia coli murI gene, which is required for the
      biosynthesis of D-glutamic acid, a specific component of bacterial peptidoglycan.
AB  - The murI gene of Escherichia coli, whose inactivation results in the inability to
      form colonies in the absence of D-glutamic acid, was identified in the 90-min
      region of the chromosome. The complementation of an auxotrophic E. coli B/r
      strain by various DNA sources allowed us to clone a 2.5-kbp EcoRI chromosomal
      fragment carrying the murI gene into multicopy plasmids. The murI gene
      corresponds to a previously sequenced open reading frame, ORF1 (J. Brosius, T. J.
      Dull, D. D. Sleeter, and H. F. Noller. J. Bacteriol. 148:107-127, 1987), located
      between the btuB gene, encoding the vitamin B12 outer membrane receptor protein,
      and the rrnB operon, which contains the genes for 16S, 23S, and 5S rRNAs. The
      murI gene product is predicted to be a protein of 289 amino acids with a
      molecular weight of 31,500. Attempts to identify its enzymatic activity were
      unsuccessful. Cells altered in the murI gene accumulate UDP-N-acetylmuramyl-L
      alanine to a high level when depleted of D-glutamic acid. Pools of precursors
      located downstream in the pathway are consequently depleted, and cell lysis
      finally occurs when the peptidoglycan content is 25% lower than that of normally
      growing cells.

PMID- 1355771
TI  - 41st International Congress of the European Society for Cardiovascular Surgery.
      Montpellier, France, September 6-9, 1992. Abstracts.

PMID- 1355770
TI  - Pantalar and tibiotalocalcaneal arthrodesis for post-traumatic osteoarthrosis of
      the ankle and hindfoot.
AB  - Twenty-one patients had a unilateral extended arthrodesis of the ankle and
      hindfoot (a tibiotalocalcaneal procedure in thirteen patients and a pantalar
      procedure in eight) for post-traumatic osteoarthrosis or deformity, or both. The
      operation was performed through a transfibular extended lateral approach, and
      autogenous bone graft and rigid internal fixation was used. A final alignment of
      0 to 5 degrees of valgus, 0 to 5 degrees of calcaneus, and external rotation
      equal to that of the contralateral side was sought. Subjective and objective
      evaluation, including a personal interview, physical examination, and
      radiographic and dynamic pedobarographic analysis, was performed at a mean
      interval of thirty-two months (range, twenty-four to fifty-four months) after the
      operation. A solid fusion was achieved in eighteen (86 per cent) of the twenty
      one patients. There were five malunions (24 per cent) and two superficial wound
      problems (10 per cent). Of the seventeen patients who were not retired from work,
      eleven returned to work: nine to an occupation that involved standing and two to
      a sedentary occupation. Although seventeen (81 per cent) of the twenty-one
      patients reported that they were much improved, twenty (95 per cent) had some
      pain, and most benefited from modifications in shoe-wear. Patients who had had a
      tibiotalocalcaneal arthrodesis were more mobile and functioned at a higher level
      than those who had had a pantalar arthrodesis. Extended arthrodesis of the ankle
      and hindfoot is a complex, technically demanding procedure, and should be
      regarded as a salvage operation capable of producing a satisfactory result and
      usually providing a reasonable alternative to amputation.

PMID- 1355769
TI  - Lesions in two Escherichia coli type 1 pilus genes alter pilus number and length
      without affecting receptor binding.
AB  - We describe the characterization of two genes, fimF and fimG (also called pilD),
      that encode two minor components of type 1 pili in Escherichia coli. Defined, in
      frame deletion mutations were generated in vitro in each of these two genes. A
      double mutation that had deletions identical to both single lesions was also
      constructed. Examination of minicell transcription and translation products of
      parental and mutant plasmids revealed that, as predicted from the nucleotide
      sequence and previous reports, the fimF gene product was a protein of ca. 16 kDa
      and that the fimG gene product was a protein of ca. 14 kDa. Each of the
      constructions was introduced, via homologous recombination, into the E. coli
      chromosome. All three of the resulting mutants produced type 1 pili and exhibited
      hemagglutination of guinea pig erythrocytes. The latter property was also
      exhibited by partially purified pili isolated from each of the mutants. Electron
      microscopic examination revealed that the fimF mutant had markedly reduced
      numbers of pili per cell, whereas the fimG mutant had very long pili. The double
      mutant displayed the characteristics of both single mutants. However, pili in the
      double mutant were even longer than those seen in the fimG mutant, and the
      numbers of pili were even fewer than those displayed by the fimF mutant. All
      three mutants could be complemented in trans with a single-copy-number plasmid
      bearing the appropriate parental gene or genes to give near-normal parental
      piliation. On the basis of the phenotypes exhibited by the single and double
      mutants, we believe that the fimF gene product may aid in initiating pilus
      assembly and that the fimG product may act as an inhibitor of pilus
      polymerization. In contrast to previous studies, we found that neither gene
      product was required for type 1 pilus receptor binding.

PMID- 1355773
TI  - Are we really 'losing the battle'?

PMID- 1355774
TI  - VIII International Conference on AIDS: in brief.

PMID- 1355772
TI  - The establishment of polarized membrane traffic in Xenopus laevis embryos.
AB  - Delineation of apical and basolateral membrane domains is a critical step in the
      epithelialization of the outer layer of cells in the embryo. We have examined the
      initiation of polarized membrane traffic in Xenopus and show that membrane
      traffic is not polarized in oocytes but polarized membrane domains appear at
      first cleavage. The following proteins encoded by injected RNA transcripts were
      used as markers to monitor membrane traffic: (a) VSV G, a transmembrane
      glycoprotein preferentially inserted into the basolateral surface of polarized
      epithelial cells; (b) GThy-1, a fusion protein of VSV G and Thy-1 that is
      localized to the apical domains of polarized epithelial cells; and (c) prolactin,
      a peptide hormone that is not polarly secreted. In immature oocytes, there is no
      polarity in the expression of VSV G or GThy-1, as shown by the constitutive
      expression of both proteins at the surface in the animal and vegetal hemispheres.
      At meiotic maturation, membrane traffic to the surface is blocked; the plasma
      membrane no longer accepts the vesicles synthesized by the oocyte (Leaf, D. L.,
      S. J. Roberts, J. C. Gerhart, and H.-P. Moore. 1990. Dev. Biol. 141:1-12). When
      RNA transcripts are injected after fertilization, VSV G is expressed only in the
      internal cleavage membranes (basolateral orientation) and is excluded from the
      outer surface (apical orientation, original oocyte membrane). In contrast, GThy-1
      and prolactin, when expressed in embryos, are inserted or released at both the
      outer membrane derived from the oocyte and the inner cleavage membranes.
      Furthermore, not all of the cleavage membrane comes from an embryonic pool of
      vesicles--some of the cleavage membrane comes from vesicles synthesized during
      oogenesis. Using prolactin as a marker, we found that a subset of vesicles
      synthesized during oogenesis was only released after fertilization. However,
      while embryonic prolactin was secreted from both apical and basolateral surfaces,
      the secretion of oogenic prolactin was polarized. Oogenic prolactin was secreted
      only into the blastocoel (from the cleavage membrane), none could be detected in
      the external medium (from the original oocyte membrane). These results provide
      the first direct evidence that the oocyte synthesizes a cache of vesicles for
      specific recruitment to the embryonic cleavage membranes which are polarized
      beginning with the first cleavage division.

PMID- 1355775
TI  - Benzodiazepines as anxiolytic agents: the risks of long-term treatment.

PMID- 1355777
TI  - Abstracts of the 11th Congress of the European Association for Cranio-Maxillo
      Facial Surgery. Innsbruck, Austria, September 9-13, 1992. Abstracts.

PMID- 1355776
TI  - Genetic linkage of recessive dystrophic epidermolysis bullosa to the type VII
      collagen gene.
AB  - Generalized mutilating recessive dystrophic epidermolysis bullosa (RDEB) is
      characterized by extreme skin fragility owing to loss of dermal-epidermal
      adherence. Immunohistochemical studies have implicated type VII collagen, the
      major component of anchoring fibrils, in the etiology of RDEB. In this study, we
      demonstrate genetic linkage of the type VII collagen gene and the generalized
      mutilating RDEB phenotype. We first identified a Pvull polymorphic site by
      digestion of an amplified product of the type VII collagen gene, which was shown
      to reside within the coding region. Genetic linkage analysis between this marker
      and the RDEB phenotype in 19 affected families which were informative for this
      polymorphism showed no recombination events, and gave a maximum lod score of 3.97
      at a recombination fraction (theta) of 0, demonstrating that this DNA region is
      involved in this form of RDEB. These data provide strong evidence that the type
      VII collagen gene, which has also been linked with the dominant form of the
      disease, harbors the mutation(s) causing the generalized mutilating form of RDEB
      in these families, thus underscoring the major functional importance of type VII
      collagen in basement membrane zone stability.

PMID- 1355778
TI  - Tyrosine hydroxylase and acetylcholinesterase in the domestic pig mesencephalon:
      an immunocytochemical and histochemical study.
AB  - The mesencephalon of the young domestic pig was studied by tyrosine hydroxylase
      (TH) immunocytochemistry and acetylcholinesterase (AChE) histochemistry with
      focus on the substantia nigra (SN), the ventral tegmental area (VTA), and related
      areas. The purpose was to obtain information on the organization of the
      mesencephalic, TH immunoreactive (TH-i), and dopaminergic areas of the pig, in
      order to provide the necessary background for the possible use of the pig as an
      alternative large animal experimental model for research on Parkinson's disease,
      including the use of encapsulated pig dopaminergic neurons for intracerebral
      xenotransplantation. Significant findings in the pig, compared to observations in
      other species, included the presence of prominent bundles of TH-i dendrites
      passing in a dorsoventral direction from pars compacta into pars reticulata at
      middle and caudal levels of the SN, and the presence of a distinct TH-i
      substantia nigra pars lateralis (SNL). Caudally in the pig mesencephalon, the
      retrorubral field (RRF) was found to be very extensive. The view of the RRF, SN,
      and VTA as parts of the same integrated system was indicated by the crisscrossing
      of TH-i dendrites at the transitions between these areas. Estimation of the
      number of TH-i neurons in the SN and the VTA showed that these nuclei were of
      equal size in the pig. Further, it was found that TH-i nerve cells were present
      in the midline between the VTA in the interfascicular and rostral linear groups.
      TH-i nerve cells were also present in the otherwise serotoninergic dorsal raphe
      nuclei, just as other TH-i cells formed a perirubral cell group. AChE-positive
      neurons were present in both SN and VTA, and appeared to have the same size and
      morphology as the TH-i neurons in these areas. Within both nuclei, there were
      local differences in the AChE staining density, but perhaps more significantly
      were some marked differences in the structure of the AChE-positive neuropil of
      the two areas. We anticipate that the present description of the cellular
      organization of the TH-i dopaminergic areas in the domestic pig ventral
      mesencephalon will be useful for the development of a nonprimate, large animal,
      experimental model of Parkinson's disease.

PMID- 1355779
TI  - CT evaluation following Whipple procedure: potential pitfalls in interpretation.
AB  - A series of 41 CT examinations in 14 patients who had undergone a Whipple
      procedure for pancreatic cancer followed by adjuvant chemotherapy and radiation
      therapy were reviewed to determine the spectrum of CT findings, as well as to
      identify potential sources of error in interpretation. Thickening of the wall of
      the gastric antrum and proximal duodenum from 5 to 10 mm (9 of 14 patients)
      occurred as early as 1 month after completion of radiotherapy and simulated
      recurrent tumor. Unopacified anastomotic bowel loops in the porta hepatis in 23
      of 41 examinations (56%) also mimicked recurrent tumor or adenopathy. Five of 14
      patients showed liver metastases and 4 of 14 had recurrent disease in the
      pancreatic bed. Pneumobilia (33 of 41 examinations) was a frequent normal
      finding.

PMID- 1355780
TI  - Powders, composed of chlorine-releasing agent acrylic resin mixtures or based on
      peroxygen compounds, for spills of body fluids.
AB  - The use of powders, composed of a mixture of a chlorine-releasing agent with
      highly absorbent acrylic resin, for disinfecting body fluid spills was evaluated
      by laboratory tests. 'Encap' and 'Red Z' were found to absorb rapidly up to 200
      ml of water to form a semi-solid gel. When experimental formulations containing
      1%, 5% and 10% available chlorine were evaluated by a standardized surface test,
      those containing 10% gave the best results. The ease and rate of absorption of
      fluids by these formulations decreased as the fluid consistency increased and
      they seem more suitable for watery spills than for blood. The use of a powder
      based on peroxygen compounds ('Virkon') for disinfecting contaminated spills was
      evaluated by laboratory tests and hospital trials. Laboratory tests showed that
      'Virkon' is strongly and rapidly bactericidal. In hospital ward trials by nurses
      using 'Virkon' on both natural and artificial spills, 60 of 62 contact plates
      pressed on to decontaminated surfaces proved negative, and no unpleasant fumes
      were generated when 'Virkon' was applied to urine. In another trial, 1% 'Virkon'
      solution proved very effective in decontaminating mortuary tables. Antiviral
      activity was not tested.

PMID- 1355781
TI  - A new standard for sterility testing for autoclaved surgical trays.
AB  - Sterility testing on autoclaved surgical trays provides scientific information on
      the duration for which an item can be safely stored. Previous studies were
      performed by sampling at various time-points after storage and did not take into
      account potential injuries (moving, lifting etc.) to these trays as they occur in
      a clinical setting. A standardized protocol was developed by an expert panel
      based on events which were frequently observed in the Central Sterilization area.
      We tested 600 samples in 100 surgical trays that were moved and transported
      according to the standardized protocol. Moved surgical trays were contaminated in
      8.3% of tests, a figure much higher than that reported by previous studies. These
      data suggest that current standards for sterility testing of autoclaved surgical
      trays can be improved by the addition of event-related testing.

PMID- 1355782
TI  - An 11-month incidence study of infections in wards of a district general
      hospital.
AB  - Between March 1988 and January 1989, an incidence study of infections in patients
      occupying 122 beds in a district general hospital was undertaken. Nursing notes,
      medical notes, temperature charts, drug prescription charts and laboratory
      information were reviewed three times a week to determine if patients had
      infection which met strict case definitions. In addition, the surveyor consulted
      with ward nursing and medical staff for clarification of symptoms and signs
      indicative of infection. During the study, 668 infections were identified amongst
      3326 patients. Three hundred and thirty-eight (51%) were community-acquired
      infections (CAI) and 330 hospital-acquired infections (HAI). Excluding 24 HAI
      acquired in other hospitals, the incidence rates were 9.2 HAI per 100 discharges,
      and 1.1 HAI per 100 patient days. The common types of CAI were pneumonia,
      abdominal infection and urinary tract infection. The main types of HAI were
      urinary tract infection, surgical wound infection and pneumonia. The
      microorganisms most frequently associated with CAI and HAI were Gram-negative
      bacilli.

PMID- 1355783
TI  - An analysis of the microbial flora of premature neonates.
AB  - An analysis of the microbial flora of 10 premature neonates hospitalized in a
      neonatal intensive care unit (NICU) was made. The babies had received neither
      antibiotics nor antiseptics and nine out of 10 were born by caesarean section.
      Samples were collected on the fourth or fifth day of life from 18 skin or mucosal
      sites. Detailed bacterial counts were obtained by plating out suitable dilutions
      of the samples on to selective media. Representative samples of each colony type
      were then subcultured and identified, using standard laboratory methods. Two
      hundred and fifty-six isolates of staphylococci were obtained and their
      susceptibility to 23 antibiotics tested. Only 11% of the samples were sterile.
      Coagulase-negative staphylococci (CNS) were the commonest species isolated and
      were predominant in every site studied. They were found in 79% of the samples and
      represented almost 81% of the neonates' flora. Eight species and biotypes of CNS
      were identified. In decreasing order of frequency, they comprised S. epidermidis
      (biotypes 1 and 2), S. hominis (biotype 1), S. warneri, S. haemolyticus, S.
      capitis, S. cohnii and S. hominis (biotype 2). CNS distribution appeared to be
      highly heterogeneous with no significant specificity of any species for a
      particular body site. The main quantitative and qualitative variations seemed to
      relate to the method of delivery, and the intensity and nature of exposure of the
      neonate to its local environment. A high level of antibiotic resistance was found
      among the CNS isolates (especially S. epidermidis and S. haemolyticus):
      penicillin G (96%), oxacillin (31%), erythromycin (52%) and gentamicin (28%).
      Moreover, multiresistant strains were numerous, supporting the nosocomial origin
      of CNS.

PMID- 1355784
TI  - In-vitro evaluation of povidone-iodine and chlorhexidine against methicillin
      resistant Staphylococcus aureus.
AB  - The in-vitro activity of povidone-iodine (PVP-I) and chlorhexidine (CHX) against
      33 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) was
      evaluated by a quantitative suspension test method. Bactericidal potency was
      measured by the logarithmic reduction factors (LRFs) achieved with each strain,
      tested at dilutions 25-800 over exposure times 30-300 s using a challenge of
      approximately 10(7) colony forming units (cfu) ml-1. The mean LRFs achieved over
      all dilutions, times and strains were significantly higher for PVP-I than CHX.
      PVP-I exhibited a superior killing effect whether measured by rate of kill or
      final LRF achieved. This difference was highly significant as judged by analysis
      of variance (P less than 0.001). Full efficacy of an antiseptic has been defined
      as a safe LRF greater than five. Over the dilution range 25-200 this was achieved
      by CHX with only three of 33 strains. In contrast, PVP-I achieved full efficacy
      with all 33 strains.

PMID- 1355785
TI  - Melioidosis and safety in the clinical laboratory.
AB  - Human infection with Pseudomonas pseudomallei, the causative agent of
      melioidosis, typically produces subclinical disease and an asymptomatic carrier
      state; occasionally clinical illness, frequently with a fatal outcome, may occur.
      Consequently, to help protect staff from laboratory-acquired melioidosis,
      microbiological and biomedical laboratories must have adequate facilities for
      safe work procedures and laboratory staff must engage in safe work practices.
      Recommendations from a melioidosis-endemic, diagnostic laboratory for the
      prevention of laboratory-acquired infection with this bacterium are essentially
      Category 3 (Advisory Committee on Dangerous Pathogens), Risk Group 3 (Australian
      Standards) or Biosafety Level 2 (National Institutes of Health) precautions.
      These include safeguards for centrifugation, prohibiting the 'sniff' test and the
      use of a biological safety cabinet for sputum processing, for subculture of stock
      strains, for preparation of antigen and for research studies but not for routine
      diagnostic techniques with P. pseudomallei.

PMID- 1355786
TI  - Methicillin-resistant Staphylococcus aureus carriage in a surgeon.

PMID- 1355787
TI  - Prophylactic antibiotics for transhepatic cholangiography?

PMID- 1355788
TI  - Lectinophagocytosis of type 1 fimbriated (mannose-specific) Escherichia coli in
      the mouse peritoneum.
AB  - Bacteria can bind specifically to phagocytic cells via lectin-carbohydrate
      interactions and such binding is often followed by activation and degranulation
      of the phagocytes, as well as uptake and killing of the bacteria, a phenomenon
      designated lectinophagocytosis. Although extensively studied in vitro, no direct
      evidence for the occurrence of lectinophagocytosis in vivo has been available. To
      obtain such evidence, we injected type 1 fimbriated (mannose-specific) or
      nonfimbriated Escherichia coli into the peritoneal cavity of mice (10(7)-10(10)
      bacteria/animal) in the absence or presence of sugars and quantified the
      phagocytic activity by assaying the release of lysosomal N-acetyl-beta-D
      glucosaminidase into the peritoneal fluid, up to 45 min after injection.
      Following injection of the type 1 fimbriated bacteria, significant release of the
      enzyme was observed which was time dependent and increased with the number of
      bacteria injected, whereas the nonfimbriated bacteria caused only little release.
      Methyl alpha-D-mannoside (50 mM), but not methyl alpha-D-galactoside or sucrose,
      inhibited the release by 60 to 100%. No release of N-acetyl-beta-D
      glucosaminidase was induced by bacteria injected into a peritoneal cavity from
      which the macrophages had been removed. Our findings show that
      lectinophagocytosis can occur in vivo and may contribute to the host's defence
      against type 1 fimbriated bacteria.

PMID- 1355789
TI  - Effects of gold(I) antiarthritic drugs and related compounds on Pseudomonas
      putida.
AB  - The effects of the antiarthritic drugs aurothiomalate (AuTm), aurothioglucose
      (AuTg), auranofin, its metabolite triethylphosphinegold(I)thioglucose (Et3PAuTg),
      and several related complexes on the growth of Pseudomonas putida were studied.
      Two strains were used, one of which (BK135) was more sensitive to Et3PAuTg
      (tolerant up to 4 microM) than the other (BK403; tolerant to at least 500
      microM). Gold thiolate complexes and thiolate ligands alone had little effect on
      growth. Gold phosphine complexes increased the length of the lag phase of growth
      and reduced oxygen uptake. Marked changes in cellular morphology were determined
      by electron microscopy. Copper(II) compounds and aurothiomalate were synergistic
      in their growth inhibitory effects towards these bacteria. Experiments with 195Au
      suggested that a mechanism does not exist for the short term (minutes) uptake of
      gold by sensitive or resistant bacteria, but the resistant strain appeared to
      limit gold uptake over a longer term (hours).

PMID- 1355790
TI  - Prediction of affected MEN2A gene carriers by DNA linkage analysis for early
      total thyroidectomy: a progress in clinical screening program for children with
      hereditary cancer syndrome.
AB  - The gene predisposing to multiple endocrine neoplasia type 2A (MEN 2A) has been
      assigned to chromosome 10, and affected gene carriers can be identified before
      the development of associated malignancy in some informative families. We applied
      these advances in gene mapping to clinical screening for possible pediatric
      surgery. A family with MEN 2A, consisting of 88 members and their spouses, was
      studied to test the reliability of the provocation of plasma calcitonin with
      pentagastrin and the possibility of DNA diagnosis of mutated gene carriers with
      DNA probes closely linked to the MEN2A gene including RBP3 and FNRB genes.
      Nineteen of the 88 were diagnosed as MEN 2A carriers. Twelve of them were treated
      surgically and the others died of medullay thyroid carcinoma (MTC) or
      pheochromocytoma. A strikingly sensitive response of calcitonin was observed in
      all those with MTC. The genotypes cosegregating with the abnormal allele at MEN2A
      in this family could be deduced from clinically established affected members. The
      early detection of gene carriers allows us to concentrate our screening efforts
      on children at high risk and to release non gene carriers from repeated
      unnecessary testing. MEN2A is one of the first cancer syndromes for which DNA
      screening permits early detection of members at high risk.

PMID- 1355791
TI  - High-performance liquid chromatographic method for determination of ronactolol in
      urine and plasma: evaluation of pharmacokinetic parameters in healthy humans.
AB  - Ronactolol [(+/-)-4'-[2-hydroxy-3-(isopropylamino)propoxy]-p-anisanilide], a new
      aminopropanol derivative showing beta-adrenoreceptor blocking activity, was
      administered orally as capsules to healthy humans at three single doses (30, 60,
      and 120 mg). Two HPLC methods were developed separately for determination of drug
      levels in urine and plasma. For plasma samples, after addition of internal
      standard (IS), a single-step extraction of alkalinized plasma was performed with
      methylene chloride. The organic layer was evaporated to dryness under reduced
      pressure, and the residue was taken up and chromatographed on a microbore silica
      column. Ronactolol and IS were detected by a UV detector at a wavelength of 278
      nm. Excellent linearity was observed between the peak height ratios
      (ronactolol:IS) and concentrations in plasma. The lowest limit of detection
      (signal:noise, 3:1) was 1.5 ng/mL of plasma. Urine samples were directly injected
      and chromatographed on a microbore C18 column with an ion-pairing mobile phase.
      Excellent linearity was observed between the peak areas and concentrations in
      urine. The lowest limit of detection (signal:noise, 3:1) was 75 ng/mL of urine.
      The assay was used to determine the main pharmacokinetic parameters in healthy
      humans.

PMID- 1355792
TI  - Opportunities for integration of pharmacokinetics, pharmacodynamics, and
      toxicokinetics in rational drug development.

PMID- 1355793
TI  - Two types of glutamate receptors differentially excite amacrine cells in the
      tiger salamander retina.
AB  - 1. Excitatory inputs to amacrine cells in the salamander retinal slice
      preparation were examined using whole-cell patch pipette voltage-clamp
      techniques. In strychnine (500 nM) and bicuculline (100 microM), two types of
      amacrine cell were easily distinguished by their light-evoked excitatory
      responses: transient and sustained. 2. In transient amacrine cells the current
      voltage (I-V) relation for the peak light-evoked current was non-linear with a
      negative slope region between -50 and -70 mV. Responses reversed near +10 mV and
      were prolonged at more positive holding potentials. 3. In DL-2-amino
      phosphonoheptanoate (AP7, 30 microM), a selective N-methyl-D-aspartate (NMDA)
      receptor antagonist, both the negatively sloped region of the light I-V relation
      and the prolongation of the response at positive potentials were eliminated. In 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2 microM), a selective non-NMDA
      receptor antagonist, light-evoked currents at the most hyperpolarized holding
      potentials were eliminated. At potentials positive to -85 mV the light-evoked
      currents lacked a fast onset. The light I-V relation in CNQX had a negative slope
      region between -35 and -80 mV. 4. With synaptic transmission blocked, kainate
      evoked responses in transient cells with a resultant I-V relation that was nearly
      linear, whereas glutamate and NMDA elicited responses with non-linear I-V
      relations. 5. Light-evoked currents in sustained amacrine cells had a nearly
      linear I-V relation and reversed near +10 mV. AP7 at a concentration of 30 microM
      did not affect the light-evoked currents in sustained cells, but 2 microM-CNQX
      eliminated all light-evoked currents in these cells. 6. With synaptic
      transmission blocked, sustained amacrine cells responded only to glutamate and
      kainate, not NMDA. The resultant I-V relations were linear. 7. We conclude that
      the light-evoked responses of transient amacrine cells are mediated by
      concomitant activation of both non-NMDA and NMDA receptors whereas the responses
      of sustained amacrine cells are mediated only by non-NMDA receptors. Furthermore,
      these data provide supportive evidence that the primary light-evoked excitatory
      neurotransmitter activating amacrine cells is glutamate.

PMID- 1355794
TI  - HIV-associated oral lesions; immunologic, virologic and salivary parameters.
AB  - There are numerous reports of oral lesions in HIV-infected individuals. However,
      few correlate the oral lesions with laboratory parameters. This study examined
      oral candidiasis and hairy leukoplakia, the two most common HIV-associated oral
      lesions, in relation to T-cell counts, p24 core antigen levels and salivary flow
      rates. Oral mucosal examinations, immunologic and virologic studies and
      stimulated whole and parotid saliva flow rates were conducted on 135 (HIV+ = 102,
      HIV- = 33) homosexual or bisexual men. Results indicate that, among HIV-infected
      subjects, the odds of having oral candidiasis is 6 times (95% CI = 0.6-56.6)
      greater for subjects with T4 counts between 200-399 per mm3, and 23 times (95% CI
      = 2.8-193.0) greater for subjects with T4 counts less than 200/mm3 compared to
      subjects with T4 counts of 400/mm3 or greater. Subjects had an equal likelihood
      of having hairy leukoplakia at different levels of immunocompetence. The
      prevalence of oral candidiasis and hairy leukoplakia was higher among subjects
      with infectious virus in their serum, but was only statistically significant for
      hairy leukoplakia (p = 0.01).

PMID- 1355795
TI  - Presence of expression products of c-erbB-1 and c-erbB-2/HER2 genes on mammalian
      sperm cell, and effects of their regulation on fertilization.
AB  - The present study was conducted to investigate the presence of expression
      products of c-erbB-1 and c-erbB-2/HER2 genes on mammalian sperm cell, and study
      the effects of their antibodies on fertilization. The mature sperm cells from
      various mammalian species (human, mouse, rabbit and rat) were found to have EGF
      receptors but not the p185HER2 molecules by indirect immunofluorescence technique
      (IFT) and Western blot procedure. Though the EGF-receptors present on sperm cells
      were functionally active and responded to ligand binding, their activation by EGF
      or blocking by antibodies did not affect the sperm cells in acquiring their
      fertilization potential. These results indicate that the products of c-erbB-1 and
      c-erbB-2/HER2 genes, though they have been shown to have tyrosine kinase enzyme
      activity, do not seem to play a major role in the development of the fertilizing
      capacity of sperm cells.

PMID- 1355797
TI  - Zinc supplements in breastfed infants.
AB  - Among breastfed infants, growth faltering in comparison with reference growth
      curves is common in both developing and developed countries. We performed a zinc
      supplementation trial in Paris, France, to find out whether such growth faltering
      is due to nutritional zinc deficiency. 57 breastfed infants aged 4-9 (mean 5.7)
      months were randomly assigned to receive either 5 mg zinc daily or a placebo for
      3 months. Most of the infants were from low-income immigrant families and the
      majority were of African origin. Before supplementation there were no significant
      differences between the zinc and placebo groups in weight, length, or
      corresponding Z-scores for age. After 3 months' supplementation, the length-for
      age Z-score had increased in the zinc group and fallen in the placebo group
      (+0.21 vs -0.13, p = 0.029). This difference was due mainly to greater linear
      growth of boys in the zinc than in the placebo group (6.0 vs 4.6 cm, p = 0.02).
      Weight gain was also significantly greater with zinc supplementation (1.64 vs
      1.28 kg, p = 0.047). Among infants breastfed for longer than 4 months, decreases
      in growth velocity result partly from inadequate zinc intake.

PMID- 1355796
TI  - Expression of the CD11/CD18 cell surface adhesion glycoprotein family and MHC
      class II antigen on blood monocytes and alveolar macrophages in interstitial lung
      diseases.
AB  - The expression of molecules of the CD11/CD18 cell surface adhesion glycoprotein
      family and HLA/DR antigen was studied on peripheral blood monocytes (PBM) and
      alveolar macrophages (AM) in bronchoalveolar lavage (BAL) fluid from patients
      with sarcoidosis, idiopathic pulmonary fibrosis (IPF), and extrinsic allergic
      alveolitis (EAA). Patients with these interstitial lung diseases showed increased
      numbers of macrophages in BAL fluid. This was probably caused by an increased
      influx of PBM to the alveoli since the numbers of cells with a monocytic
      morphology were also significantly increased in BAL samples from patients with
      interstitial lung disease, most prominently in IPF and EAA. The increased influx
      of PBM into the alveoli in patients with interstitial lung diseases was not
      reflected by an increased expression of the CD11/CD18 leukocyte function antigens
      on PBM. In healthy volunteers as well as in those with sarcoidosis, IPF, and EAA,
      the percentages of AM positive for CD11b (the C3bi complement receptor) and CD11c
      were lower than among PBM. This indicates that the expression of these cell
      surface adhesion molecules is downregulated during maturation and migration of
      PBM to the alveoli. The absolute numbers of AM positive for CD11b were increased
      in BAL fluid of IPF and EAA patients compared to healthy volunteers. EAA patients
      also showed increased absolute numbers of AM positive for CD11a and CD11c. This
      differentially increased expression of these leukocyte function antigens on AM
      suggests the influence of locally produced cytokines.

PMID- 1355798
TI  - Safety and immunogenicity of single-dose live oral cholera vaccine CVD 103-HgR in
      5-9-year-old Indonesian children.
AB  - Oral vaccines offer great promise as public-health measures to prevent disease in
      less-developed countries. CVD 103-HgR, a genetically engineered, attenuated,
      Vibrio cholerae O1 strain has proved effective in industrialised countries. We
      have assessed the safety, immunogenicity, and excretion of this live cholera
      vaccine in children in north Jakarta, Indonesia. 412 children aged 5-9 years
      received single doses of 5 x 10(6), 5 x 10(7), 5 x 10(8), 5 x 10(9), or 1 x
      10(10) colony forming units (CFU) of CVD 103-HgR or placebo (5 x 10(8)
      inactivated Escherichia coli K-12) with buffer. All doses were well tolerated.
      The 5 x 10(8) CFU dose, which is highly immunogenic in subjects in industrialised
      countries (greater than 90% seroconversion), elicited seroconversions of
      vibriocidal antibody in only 16% of Indonesian children. By contrast, a single 5
      x 10(9) CFU dose of vaccine resulted in high rates (75% and 87%) of
      seroconversion with two different batches of vaccine. A batch prepared with a
      centrifugation step gave significantly higher geometric mean titres (16-fold
      increase over baseline) than did a batch in which there was a filtration step
      between fermentation and lyophilisation (10-fold increase over baseline). At a 5
      x 10(9) CFU dose, CVD 103-HgR is well tolerated and highly immunogenic in
      Indonesian children and should therefore be further investigated for use as a one
      dose live oral cholera vaccine in developing countries.

PMID- 1355799
TI  - Effects of exposure to benzodiazepine during fetal life.
AB  - Dysmorphism and mental retardation have been reported in 7 Swedish children born
      of mothers who had taken high doses of benzodiazepines regularly during
      pregnancy. To explore this association further, we examined benzodiazepine use
      during pregnancy in 104,000 women whose deliveries were registered by the US
      public health insurance system, Medicaid, during 1980-83. Fetal outcomes were
      assessed from the health claims profiles of their offspring, up to 6-9 years
      after delivery. 80 pregnant women had received 10 or more benzodiazepine
      prescriptions during the 4 years. Their records showed heavy general use of
      health care and frequent alcohol and substance abuse, and other disorders that
      could confound any effect of the benzodiazepines. For the 80 pregnancies, 3
      intrauterine deaths were identified as well as 2 infants with congenital
      abnormalities whose curtailed records suggested neonatal death. Records of 64
      surviving children could be linked to these 80 pregnancies whilst records for 11
      apparent survivors could not be located. 6 of the 64 survivors had diagnoses
      consistent with teratogenic abnormalities. The high rate of teratogenicity after
      heavy maternal benzodiazepine use occurs with multiple alcohol and substance
      exposure and thus may not be due to benzodiazepine exposure.

PMID- 1355800
TI  - Stereoselective release of (S)-atenolol from adrenergic nerve endings at
      exercise.
AB  - In-vitro studies have shown that atenolol, a beta-blocking agent, is
      stereoselectively taken up by and released from adrenergic nerve endings by
      membrane depolarisation. To investigate the potential importance of these
      findings, blood samples were taken at rest and after exercise testing from 10
      patients (mean [SE] age 60 [3] years) receiving long-term treatment with racemic
      atenolol. At rest, mean plasma concentration of (R)-atenolol was higher than that
      of (S)-atenolol (ratio 1.14, p less than 0.01), but after exercise there was a
      stereoselective increase in (S)-atenolol concentration, which changed the ratio
      to 0.66 (p less than 0.01). Since (S)-atenolol but not (R)-atenolol causes
      clinically relevant beta-blockade, our findings may have importance for the
      management of patients receiving beta-blocking drugs.

PMID- 1355802
TI  - Organising pneumonia: COP/BOOP and SOP.

PMID- 1355801
TI  - Hepatitis C viraemia and liver disease in symptom-free individuals with anti-HCV.
AB  - There is controversy about clinical management of patients who persistently have
      antibodies to hepatitis C virus (anti-HCV) but who have no symptoms and signs of
      liver disease. We have taken liver biopsy samples from 23 such patients (16 of
      whom had normal alanine aminotransferase [ALT] values) to assess prevalence of
      liver disease and to see whether anti-HCV and HCV-RNA correlated with
      histological findings. 16 patients had histological evidence of chronic
      hepatitis, which was not predicted by serum ALT or by the pattern of specificity
      of anti-HCV. All 16 cases with hepatitis C viraemia (HCV-RNA detected by
      polymerase chain reaction), including 9 with normal ALT, had chronic hepatitis on
      biopsy (p less than 0.001), whereas 7 HCV-RNA-negative cases had normal liver
      histology. These findings indicate that serum HCV-RNA is a sensitive and specific
      marker of liver disease in anti-HCV-positive subjects, independent of ALT values,
      and challenge the idea of the existence of "true" healthy carriers of HCV.

PMID- 1355803
TI  - Depression and suicide: are they preventable?

PMID- 1355805
TI  - Cystic fibrosis mice.

PMID- 1355806
TI  - Community approach to psychiatric illness.

PMID- 1355804
TI  - Loin pain/haematuria syndrome.

PMID- 1355807
TI  - Ultrasonographically detectable markers of fetal chromosomal abnormalities.
AB  - Screening for fetal chromosomal abnormalities on the basis of maternal age has
      not resulted in a substantial fall in the proportion of infants born with an
      abnormal karyotype. Most fetuses with major chromosomal abnormalities have
      defects that can be recognised on detailed ultrasonographic examination.
      Therefore, provided the cardinal signs of each chromosomal syndrome are
      recognised, it is possible that screening by ultrasound examination could have a
      greater impact. We karyotyped 2086 fetuses after ultrasonographic examination had
      revealed fetal malformations, growth retardation, or both. Chromosomal
      abnormalities were detected in 301 (14%) cases and were more common among fetuses
      with multisystem malformations (29%) than among those with isolated defects (2%).
      The commonest chromosomal abnormality was trisomy 18, followed by trisomy 21,
      triploidy, Turner's syndrome, unbalanced chromosomal rearrangements, and trisomy
      13. Trisomy 18 was associated with strawberry-shaped head, choroid plexus cysts,
      facial cleft, micrognathia, heart defects, exomphalos, malformations of hands and
      feet, and growth retardation. In trisomy 21, the associated defects were subtle
      and included nuchal oedema, macroglossia, atrioventricular septal defects, mild
      hydronephrosis, clinodactyly, and sandal gap. The frequency of autosomal
      abnormalities increased with maternal age, but if fetal karyotyping had been
      restricted to mothers older than 35 years, large proportions of chromosomally
      abnormal fetuses would not have been diagnosed prenatally (64-97%). Our findings
      provide guidelines as to which defects to search for in screening studies for the
      detection of chromosomal abnormalities.

PMID- 1355808
TI  - HIV infection at outcome of pregnancy in the Paris area, France.
AB  - The prevalence of HIV infection in women at end of pregnancy, irrespective of
      outcome, was determined in a comprehensive survey of both women and medical
      centres during successive 4-week periods in four areas of the Paris region,
      France. Blood samples were tested anonymously for antibodies to human
      immunodeficiency virus (HIV)-1 and HIV-2. Of the 11,593 blood samples 0.40% (95%
      confidence interval [CI] 0.28-0.51) were positive for HIV-1 and 0.02% (95%
      binomial interval [BI] 0.002-0.065) for HIV-2. Seroprevalence was higher among
      women with ectopic pregnancy (2%) (95% BI 0.24-7.04); the rate in women having an
      elective or therapeutic abortion was more than twice that in those delivering
      babies (0.70% vs 0.28%, p less than 0.05, relative risk 2.54, 95% CI 1.36-4.75).
      Studies with neonatal HIV seroprevalence as a surrogate for HIV prevalence in
      pregnant women would underestimate prevalence in these women.

PMID- 1355809
TI  - Smoking as "independent" risk factor for suicide: illustration of an artifact
      from observational epidemiology?
AB  - Two widely used criteria for determining whether an association between a risk
      factor and a disease is causal are dose response and independence from other
      factors. Data from a large US risk factor study (MRFIT) throw up a relation
      between cigarette smoking and suicide that meets these criteria, yet appears to
      be biologically implausible. It is likely that many more such associations, for
      other exposures and other diseases, are equally spurious, but are protected by
      their lack of obvious implausibility.

PMID- 1355811
TI  - Health care on the campaign trail.

PMID- 1355810
TI  - Extraordinary unremitting endurance exercise and permanent injury to normal
      heart.
AB  - This hypothesis is that permanent cardiac injury could develop in some endurance
      athletes despite the absence of coronary atherosclerosis and ventricular
      hypertrophy. The proposed mechanism by which this injury could arise involves two
      physiological "vicious cycles". The first vicious cycle would occur between
      severe ischaemia and high catecholamines, the second would be between coronary
      vasospasm (induced by high catecholamines) and endothelial injury. The likelihood
      of the injury becoming permanent might increase if there is insufficient time
      between bouts of endurance exercise for regression of ischaemia and endothelial
      repair. Furthermore, magnesium ion deficiency, which can be induced by exercise,
      could exacerbate these vicious cycles and also contribute to catecholamine
      induced thrombogenesis. In addition to ischaemia, there are several mechanisms,
      including the effect of free fatty acids liberated by the lipolytic effect of
      high catecholamines, that could cause direct myocardial injury.

PMID- 1355812
TI  - Cautionary tales from gynaecology and obstetrics.

PMID- 1355813
TI  - Binge-eating and polycystic ovaries.

PMID- 1355814
TI  - Amblyopia and yellow spectacles.

PMID- 1355815
TI  - Carcinogenicity of 1,3-butadiene.

PMID- 1355816
TI  - Signs of falanga torture.

PMID- 1355817
TI  - Complications of "ecstasy" misuse.

PMID- 1355818
TI  - Complications of "ecstasy" misuse.

PMID- 1355819
TI  - Complications of "ecstasy" misuse.

PMID- 1355820
TI  - Serum cardiac troponin T in polymyositis/dermatomyositis.

PMID- 1355821
TI  - Cerebrospinal fluid immunocytology in primary central nervous system lymphoma.

PMID- 1355822
TI  - Low-density lipoprotein oxidation and coronary atherosclerosis.

PMID- 1355823
TI  - Loss of taste and terbinafine.

PMID- 1355824
TI  - Prevention of staphylococcal septicaemia in very-low-birthweight infants.

PMID- 1355825
TI  - Pefloxacin as first-line treatment in nephrotic syndrome.

PMID- 1355826
TI  - Toxic leucoencephalopathy after heroin ingestion in a 21/2-year-old child.

PMID- 1355827
TI  - Acute neuropathy in perazine-treated patients after sun exposure.

PMID- 1355828
TI  - Coronary lesions in young HIV-positive subjects at necropsy.

PMID- 1355829
TI  - Apolipoprotein AII in HIV-1 infection.

PMID- 1355831
TI  - Charging for health services in developing countries.

PMID- 1355830
TI  - Disseminated Mycobacterium avium intracellulare infection without predisposing
      conditions.

PMID- 1355832
TI  - Charging for health services in developing countries.

PMID- 1355833
TI  - Organ procurement in Spain.

PMID- 1355835
TI  - Philosophy of science.

PMID- 1355834
TI  - Philosophy of science.

PMID- 1355836
TI  - Dental health in the USA.

PMID- 1355837
TI  - Igbinedion Hospital.

PMID- 1355838
TI  - Influence of cross-sex transmission on measles mortality in rural Senegal.

PMID- 1355839
TI  - beta-Glucuronidase antibodies in ulcerative colitis.

PMID- 1355840
TI  - Diagnosis of pseudomembranous colitis.

PMID- 1355841
TI  - HLA typing by amplification-created restriction site.

PMID- 1355842
TI  - Exclusion of false-positive PCR viral diagnosis by single-strand conformation
      polymorphism.

PMID- 1355843
TI  - Laparoscopic pericardial fenestration.

PMID- 1355844
TI  - Testing for neutralising potential of serum antibodies to tetanus and diphtheria
      toxin.

PMID- 1355845
TI  - Lymphocyte beta-adrenoceptors, asthma, and ethnicity.

PMID- 1355846
TI  - Steroid anaesthetic agents.

PMID- 1355847
TI  - Indoor radon exposure and cytogenetic damage.

PMID- 1355848
TI  - Prenatal diagnosis of tyrosinase-negative oculocutaneous albinism.

PMID- 1355849
TI  - Chlorine and survival of "rugose" Vibrio cholerae.

PMID- 1355850
TI  - Acute changes in growth hormone-releasing hormone secretion after injection of
      BIM 23014, a long acting somatostatin analog, in rams.
AB  - BIM 23014 is a somatostatin analog displaying an increased biological half life
      due to resistance to enzymatic degradation. This peptide inhibits GH release
      directly at the level of pituitary somatotrophs. In addition, an action of BIM
      23014 at the level of the hypothalamus is possible since somatostatinergic fibers
      and receptors have been identified on GH-RH neurons. To evaluate the effect of
      BIM 23014 on GH-RH secretion, hypophysial portal blood (HPB) was continuously
      collected in conscious sheep. Twelve rams (40-45 kg, 9-month-old) with
      chronically implanted perihypophysial cannulae were i.v. injected with BIM 23014
      (1 mg) or saline. HPB and jugular blood were collected for 3-5 hours before and
      after the injection for the determinations of GH-RH and GH concentrations
      respectively. The acute injection of BIM 23014 induced a rapid decrease of plasma
      GH within the first two hours. Simultaneously, GH-RH in HPB decreased
      significantly. After reaching a nadir, GH concentrations increased to values
      greater than baseline. A similar rebound in GH-RH levels in HPB was also
      observed. These data indicate that BIM 23014 acts at the level of GH-RH
      hypothalamic neurons, in addition to its well-know effect on the pituitary gland.

PMID- 1355851
TI  - Tyr-MIF-1 and hemorphin can act as opiate agonists as well as antagonists in the
      guinea pig ileum.
AB  - The brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) was tested for its effects on
      electrically stimulated contractions in the guinea pig ileum assay. Tyr-MIF-1
      acted as an opiate agonist in reducing these contractions. Its IC50 was about 9
      microM, and its effects were reversed by naloxone and CTOP. The ability of Tyr
      MIF-1 also to antagonize the inhibitory effects of opiates on electrically
      stimulated contractions was more evident in the ileum removed from a guinea pig
      tolerant to morphine or after partial inactivation of opiate receptors with beta
      CNA. Similar results were observed with hemorphin. The endogenous peptide Tyr-MIF
      1 and the blood-derived peptide hemorphin, therefore, can act as agonists as well
      as antagonists in the guinea pig ileum. The effects as antagonists are best
      observed in preparations of ileum with reduced receptor reserve (tolerant or beta
      CNA treated) and are consistent with the idea that properties of endogenous
      peptides as opiate antagonists are enhanced in the tolerant state.

PMID- 1355852
TI  - Type 1 pili enhance the invasion of Salmonella braenderup and Salmonella
      typhimurium to HeLa cells.
AB  - The relationship between type 1 pili-associated adhesion and invasion to HeLa
      cells by Salmonella braenderup and S. typhimurium was studied. When the clinical
      isolates of these strains were grown in L-broth, they showed both type 1 pili
      formation and mannose-sensitive adhesion to HeLa cells. On the other hand, the
      type 1 pili-defective mutants, which were obtained either by repeated subcultures
      on L-agar plates or by the transposon Tn1-insertion mutagenesis of the S.
      braenderup and S. typhimurium strains, concomitantly lost mannose-sensitive
      adhesion to HeLa cells. When the HeLa cells were incubated with Salmonella, the
      type 1 piliated strains invaded the HeLa cells with much higher infection rate
      than did the type 1 pili-defective strains. The invasion of type 1 piliated
      strains to HeLa cells was markedly inhibited in the presence of D-mannose. The
      infectivity of the strain, which lost type 1 pili but still had mannose-resistant
      adhesion, was slightly higher than that of the strains defective in both mannose
      sensitive and mannose-resistant adhesion. These results suggested that type 1
      pili have a role in enhancing the invasion of S. braenderup and S. typhimurium to
      HeLa cells.

PMID- 1355853
TI  - Response to 2-chlorodeoxyadenosine in patients with B-cell chronic lymphocytic
      leukemia resistant to fludarabine.
AB  - BACKGROUND: Patients with untreated B-cell chronic lymphocytic leukemia have a
      high rate of complete remission when given the halogenated nucleoside analogue
      fludarabine. However, patients in whom the disease has proved refractory to
      primary treatment have a reduced life expectancy and a dismal outcome. METHODS:
      We treated four consecutive patients who had unsatisfactory responses to second
      line or subsequent treatment with fludarabine with another halogenated nucleoside
      analogue, 2-chlorodeoxyadenosine. RESULTS: One patient with progressing
      lymphocytosis, anemia, and thrombocytopenia despite 10 courses of fludarabine
      entered a complete remission when treated with 2-chlorodeoxyadenosine. Two
      patients who had less-than-partial remissions after six courses of fludarabine
      had good partial remissions when treated with 2-chlorodeoxyadenosine. One patient
      with Coombs-positive hemolytic anemia who had no response to three courses of
      fludarabine had a partial remission, with resolution of hypogammaglobulinemia,
      when treated with 2-chlorodeoxyadenosine. CONCLUSIONS: There was no evidence of
      cross-resistance between fludarabine and 2-chlorodeoxyadenosine despite their
      similar structures. 2-Chlorodeoxyadenosine may induce a complete remission in
      chronic lymphocytic leukemia that is highly resistant to chemotherapy, and it
      deserves wider clinical evaluation in patients with this condition.

PMID- 1355854
TI  - Infection breaks T-cell tolerance.
AB  - Clonal deletion or clonal anergy establish tolerance in T cells that bear
      potentially autoreactive antigen receptors. Here we report that concomitant
      infection with the nematode Nippostrongylus brasiliensis breaks an established T
      cell tolerance induced by injection of mice with Staphylococcus enterotoxin B
      (SEB). CD4+ T cells from SEB-tolerant mice did not produce either interleukin-2
      or interleukin-4 when challenged in vitro with SEB. N. brasiliensis infection of
      SEB-primed animals resulted in a normal expansion of SEB-tolerant CD4+V beta 8+ T
      cells in vivo as well as an equivalent increase of SEB-reactive, interleukin-4
      producing CD4+V beta 8+ T cells both in SEB-tolerant and in normal animals. Thus,
      infection with N. brasiliensis circumvented the tolerance established with SEB.
      Activation of anergic, potentially autoreactive CD4+ T cells by infectious agents
      seems to be a major pathway for the initiation of autoimmune diseases. Our
      results suggest that infectious agents may break tolerance in potentially
      autoreactive CD4+ T cells by activation of alternative reaction pathways.

PMID- 1355855
TI  - Virulent strains of Toxoplasma gondii comprise a single clonal lineage.
AB  - The protozoan Toxoplasma gondii is a prevalent parasite in wild and domestic
      animals worldwide, being transmitted through the food chain by carnivorous
      feeding and scavenging. Toxoplasma normally divides asexually to yield a haploid
      form that can infect virtually any vertebrate but it also has a well defined
      sexual cycle that occurs exclusively in cats. Toxoplasma has become important as
      an often fatal opportunistic pathogen in patients with AIDS, although the 15-85%
      of adult human populations that are chronically infected with T. gondii are
      typically asymptomatic. Infections in immunocompromised hosts have variable
      outcomes. For example, only 30 to 50% of AIDS patients that are chronically
      infected with the parasite develop toxoplasmic encephalitis and only about half
      of acute maternal infections result in congenital disease of the newborn. T.
      gondii strains differ in their virulence in animals, but the extent to which
      different strains are related has not been determined. Here we analyse 28 strains
      from a variety of hosts on five continents and find that the ten virulent strains
      have an essentially identical genotype, whereas the nonvirulent strains are
      moderately polymorphic. These data strongly suggest that virulent strains of T.
      gondii originated from a single lineage which has remained genetically
      homogeneous despite being globally widespread, and despite the ability of this
      organism to reproduce sexually.

PMID- 1355856
TI  - Neurotransmitters. ATP joins the fast lane.

PMID- 1355857
TI  - A meiotic gene conversion gradient opposite to the direction of transcription.
AB  - Genetic recombination involves classical crossing-over and gene conversion
      (aberrant segregation). In fungi that produce an ascus containing four spores, a
      gene conversion event is manifested as 3:1 or 1:3 (or more rarely 4:0 or 0:4)
      segregations, in contrast to the normal mendelian 2:2 segregation. Polarity is
      one of the properties of gene conversion; in almost all cases the frequency of
      conversion exhibits a gradient across the gene monitored. The frequency of
      conversion is usually independent of the specific allele used as a marker, but
      dependent on its location. An interpretation of conversion polarity is that it is
      caused by the existence of specific initiation sites for meiotic recombination,
      located at the high end of the polarity gradient. Here we show that the polarity
      gradient for the HIS2 gene of Saccharomyces cerevisiae is high at the 3' end of
      the gene, implying that the promoter of HIS2 is not the initiation site.

PMID- 1355858
TI  - Aging of the serotonergic system in the rat forebrain: an immunocytochemical and
      neurochemical study.
AB  - Age-related changes in both morphological and neurochemical parameters of indol-
      and catecholaminergic system in the rat brain were examined. A qualitative
      histochemical survey of the occurrence of aberrant serotonergic fibers in the
      aged rat brain suggests region-specificity in the process of degeneration.
      Forebrain areas, such as the caudate-putamen complex, globus pallidus, prefrontal
      and frontoparietal cortices were consistently affected, whereas serotonergic
      fibers were only infrequently affected in other areas like septal and amygdaloid
      nuclei. Neurochemical data similarly revealed regional differences. 5
      Hydroxytryptamine levels were increased in the frontoparietal cortex,
      hippocampus, hypothalamus and the mesencephalic raphe region but remained
      unchanged in the caudate-putamen complex. 5-Hydroxyindolacetic acid levels were
      also enhanced in all these areas. Examination of brains of 12-, 18- and 24-month
      old rats revealed that aberrant serotonergic fibers were already present at the
      age of 12 months and their incidence increase with age. There was no difference
      in the number of serotonergic cells in the dorsal raphe nucleus of young and aged
      rats. Aberrant tyrosine hydroxylase-immunoreactive fibers were observed only
      infrequently. Their occurrence showed no overlap with the areas containing
      aberrant serotonergic fibers. Neurochemical estimates of the levels of
      catecholamines in young versus aged rat brain areas similarly revealed regional
      and neurotransmitter specific differences to occur during the process of aging.

PMID- 1355860
TI  - Coma of vascular aetiology: evaluation and prognosis.
AB  - The authors have done a revision of 450 patients admitted during the last 3 years
      to the emergency service of the Hospital de S. Jose with the diagnosis of CVA. In
      this retrospective study were included the patients of greater than or equal to 3
      degree of the RLS/85 coma scale, the diagnostic being confirmed by CAT,
      angiography and/or autopsy, and simultaneously evaluated by the Glasgow coma
      scale. The studied population was grouped into: SAH; ICH with or without
      ventricular drowning, cerebellar haematoma, brainstem haematoma, ischaemic CVA.
      The factors of vascular risk: diabetes and hypertension, the age of the patients
      and coma level were correlated with the degree of cerebral disability of
      discharge in all patients. The following factors are clearly related with bad
      prognosis: coma of degree greater than or equal to 4 in the RLS/85 scale;
      ischaemic aetiology; intraventricular haemorrhage.

PMID- 1355859
TI  - Tuberoinfundibular dopaminergic neurons and lactotropes in young and old female
      rats.
AB  - Aging in female rats is accompanied by several endocrine dysfunctions, such as
      reproductive decline associated with characteristic hyperprolactinemia,
      lactotrope hyperplasia, and functional impairment of hypothalamic
      tuberoinfundibular dopaminergic (TIDA) neurons. The aim of this morphometrical,
      immunocytochemical, and densitometrical study was to gain a better anatomical
      knowledge of TIDA neurons and axons as well as of lactotropes in old female rats
      with (A) or without (NA) pituitary adenomas, compared with young animals. At the
      hypothalamic level, we found that tyrosine hydroxylase (TH)-labeled neurons in
      the arcuate nucleus were comparable in young and old NA yet their size and TH
      content were increased in A animals. Also the TH-labeled median eminence axons
      did not differ significantly between young and old NA but were more numerous in
      the old A rats. Independently from adenomas, both number of prolactin (PRL)
      labeled structures and content of immunoreactive PRL were increased in
      pituitaries of old rats, the plasma PRL levels, however, were high only in A. Our
      findings support the documented lactotrope hypertrophy and hyperplasia in old
      female rats and suggest that TIDA-neuron changes only occur in hyperprolactinemic
      animals carrier of adenomas.

PMID- 1355861
TI  - Racial differences in coagulation studies in stroke.
AB  - Racial differences in stroke are known to exist with persons in the black race
      having a higher morbidity, mortality and incidence of stroke compared to whites.
      We evaluated coagulation factors in black and white stroke patients and compared
      the results between races. D-dimer was elevated more frequently in blacks than
      whites to a statistically significant degree. There were non-significant trends
      for blacks to have a positive lupus anticoagulant, low protein C and protein S,
      higher platelet factor 4, and hyporesponsive platelets to 10 microM epinephrine.
      The significance of these findings in understanding racial differences in stroke
      is discussed.

PMID- 1355862
TI  - Mixed type of dementia: coexistence of vascular and degenerative types.

PMID- 1355863
TI  - Heart-brain interactions in cerebral ischaemia: a non-invasive cardiologic study
      protocol.
AB  - The cardiologic evaluation of patients with cerebral ischaemia should be aimed
      at: (1) identifying potential cardiac sources for cerebral emboli, (2) detecting
      a coexisting ischaemic heart disease, even asymptomatic. The present data
      concerns a ten-year experience of a systematic cardiologic evaluation of patients
      admitted to the 1st Division of Neurosurgery, Bellaria Hospital, Bologna, Italy,
      for cerebral ischaemia. A two-dimensional echocardiography was carried out in 344
      consecutive patients (mean age 53 years), cardiac abnormalities were observed in
      92 (28%) out of the 328 cases with technically adequate examination, embologenic
      lesions in 57 (17%). In 18 cases the cardiac lesion was unknown before the
      cerebral event. An exercise ECG testing was carried out in 322 patients (mean age
      56 years), resulting in abnormal in 69 out of the 258 with adequate examination
      (17%). A subsequent exercise 201Tl myocardial scintigraphy confirmed the presence
      of ischaemic heart disease in 58 cases. Among patients unable to perform an
      adequate exercise, a dipyridamole 201Tl myocardial scintigraphy was performed in
      38 cases showing perfusional defects in 23 (60%), while a dipyridamole
      echocardiography was performed in 25 cases showing wall motion abnormalities in 9
      (36%). A 24-h Holter monitoring was performed in 65 cases: arrhythmias were
      detected in 27 patients (41%), but a correlation with the cerebral event was
      suggested only in 3 cases with atrial fibrillation. According to our experience
      patients with recent ischaemia should be submitted to the following non-invasive
      cardiologic screening: (1) exercise ECG testing followed, if abnormal or
      indeterminant, by 201Tl myocardial scintigraphy in all patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1355864
TI  - Cerebral magnetic resonance angiography.
AB  - Magnetic resonance angiography (MRA) is an accurate non-invasive tool for imaging
      the cerebral vessels. It provides morphologic information about the cerebral
      vessels relying on blood flow as the physical basis for generating contrast
      between stationary tissues and moving spins. 'Selective' MRA gives functional
      information about the cerebrovascular system such as flow direction, origin of
      flow, and presence or absence of collaterals. Arteries and veins can be imaged
      selectively due to their usually opposite flow directions. Although at a
      relatively early stage of development, MRA has already become a widely used tool
      for the study of the cerebrovascular system.

PMID- 1355865
TI  - Intra- and inter-observer variability of basal flow velocity and vascular
      reactivity measurements using transcranial Doppler sonography.
AB  - The reliability of blood flow velocity measurements performed using transcranial
      Doppler sonography was investigated with regard to the intra- and inter-observer
      variability. We compared the flow velocity values recorded in the intracranial
      vessels by two experienced investigators both under rest conditions and during
      hypercapnia induced by an apnea test. The results showed how flow velocity values
      measured at the level of the middle cerebral artery, anterior cerebral artery,
      ophthalmic artery and basilar artery were not significantly influenced by intra-
      or inter-examiner variability. The flow velocity increases recorded from the
      middle cerebral artery during the activation test proved to be reproducible when
      the measurements were repeated by the same examiner, but more variable when
      detected by different investigators. On the basis of the available data, the
      clinical relevance of transcranial Doppler results must take into account the
      degree of reliability of its measurements.

PMID- 1355866
TI  - Correlates of contralateral hypoperfusion in chronic stroke patients.

PMID- 1355867
TI  - Cerebellar blood flow involvement in temporal post-ictal epilepsy: a TC-Hm PAO
      Spect study.

PMID- 1355869
TI  - Functional 3D localization of cerebrovascular accidents by magnetoencephalography
      (MEG).
AB  - Spontaneous magnetic slow wave brain activity can be used to locate the
      underlying sources with sufficient accuracy by using the single current dipole
      model. To locate focal sources from spontaneous activity a tool had to be
      developed to extract focal densities of dipoles across time-the dipole density
      plot. The first version works on discrete volume units and is used for screening.
      The second version avoids a possible localization error and works continuously
      and this even is done on individual slices. The DDP seems to be a valuable tool
      for extracting and separating different focal sources from the background
      activity. Not only brain infarctions and haemorrhages (and cysts and angiomas)
      could be located, but also functional sources associated with TIAs even one week
      after the symptoms. First results let us assume that clinically silent TIAs also
      (in analogy to clinically silent brain infarctions) could be detected and
      located.

PMID- 1355868
TI  - Age-related decline of cerebral oxygen metabolism in normal population detected
      with positron emission tomography.
AB  - Using positron emission tomography (PET), cerebral blood flow (CBF) and cerebral
      metabolic rate of oxygen (CMRO2) were measured in 32 healthy volunteers aged from
      27 to 67 years. In bilateral putamen, left supratemporal, left infrafrontal and
      left parietal cortices, CMRO2 showed a significant decline during aging. The age
      related decline of CBF was seen only at the left superior temporal cortex. The
      mean CMRO2 was significantly lower in the elder group (over 51 years old) than in
      the younger group (under 50 years old), whereas no significant difference in mean
      CBF between the two groups. The poor correlation of CBF to the age could be
      explained partly by the fact that CBF is easily influenced by the physiological,
      psychological and/or environmental factors. The age-related changes of CMRO2 were
      more marked in the association cortices of the left hemisphere than in that of
      the right hemisphere.

PMID- 1355870
TI  - Acetazolamide stimulation test in patients with unilateral internal carotid
      artery obstructions using transcranial Doppler and 99mTc-HM-PAO-Spect.
AB  - Fifteen patients with symptoms of cerebral ischaemia and angiographically
      confirmed unilateral stenoses or occlusions of the extracranial internal carotid
      artery (ICA) and 20 controls were studied by a 2 MHz transcranial Doppler (TCD)
      at rest and after stimulation with 1 g acetazolamide i.v., a cerebral
      vasodilator. In addition, the patients underwent 99mTc-HM-PAO-Spect measurement
      of regional cerebral blood flow (rCBF) at rest and after stimulation with 1 g
      acetazolamide. In 10 patients with ICA stenoses greater than 80% or occlusions,
      time-mean velocity (Vmean) increase and pulsatility index (PI) decrease in the
      postobstructive middle cerebral artery (MCA) as well as the increase of the
      ipsilateral rCBF were reduced in comparison with the contralateral side. The
      remaining 5 patients showed a normal Vmean increase and PI decrease in TCD.

PMID- 1355871
TI  - Functional and morphological imaging of small striato-capsular infarction by CT,
      MRI and multitracer PET.
AB  - Regional cerebral blood flow, oxygen consumption, blood volume and glucose
      metabolism were studied by positron emission tomography (PET) in 16 patients with
      striato-capsular infarction during the acute phase. Visual evaluation of
      tomograms and quantitative analysis of PET data detected in all patients severe
      flow disturbances and metabolic derangement within the territory of the
      penetrating branches of the middle cerebral artery. Additionally remote effects
      were observed. The correspondence of early PET changes with the diagnosis of
      striato-capsular infarction was verified later on by computerized three
      dimensional alignment of PET scans and MRI. These results demonstrate that PET
      allows localization of small striato-capsular infarction with high accuracy in
      the acute phase by demonstrating both severe local flow disturbances and
      metabolic derangement, as well as remote effects.

PMID- 1355872
TI  - Assessment of intracranial circle after carotid endarterectomy.
AB  - To evaluate haemodynamic effects of carotid endarterectomy on cerebral
      circulation, transcranial Doppler sonography was performed on 69 patients
      operated for unilateral carotid stenosis greater than 70%. Pre- and post
      operative Vm and PI on bilateral middle-cerebral arteries, Vm PI and flow
      direction on ipsilateral anterior cerebral artery and Vm on basilar artery were
      evaluated. All patients presented more or less evident preoperative haemodynamic
      alterations of cerebral circulation and after surgery showed a normal
      distribution of cerebral blood supply.

PMID- 1355873
TI  - Blood flow hydrodynamic resistance in patients with ischaemic stroke or vascular
      encephalopathy and possibilities of its correction in vitro.
AB  - In order to determine the patient blood flow hydrodynamic properties in terms of
      the Toms-effect, the time blood flow was measured in special apparatus twice: (1)
      before and (2) after addition of poly(ethylene oxide) WSR-301 (Union Carbide,
      USA) in concentration of 2 x 10(6) g/ml of blood sample (50 ml with 500 units of
      heparin) taken from 26 patients with acute ischaemic stroke, 8 patients with
      vascular encephalopathy after stroke, 5 patients with vascular encephalopathy
      following atherosclerosis with or without arterial hypertension. The blood
      samples taken from 8 healthy persons formed the control group. Haematocrit (HCT)
      and asymptotic blood viscosity were studied also. It was established that
      hydrodynamic blood flow resistance (HBFR) did not depend on HCT and viscosity,
      but was significantly higher in all patient groups than in normal persons (p less
      than 0.05). Addition of polymer solution decreased HBFR of patient blood more
      intensively that in the control group. We believe that it indicates an
      insufficiency of an unidentified factor in native human blood.

PMID- 1355874
TI  - Modalities of compensation of cerebral circulation through the circle of Willis
      in stenoses and occlusions of extracranial arteries.
AB  - We have studied the intracranial cerebral circulation in 6 patients with
      bilateral ischaemic lesions of the internal carotid artery in the extracranial
      segment (2 significant bilateral stenosis cases; 1 case with bilateral thrombosis
      and 3 cases of unilateral thrombosis and significant contralateral stenosis). All
      the patients were males, their age being between the 5th and 8th decade. In a
      single case the neurological examination showed secondary left hemiplegia and
      recent right paresis of remittent type, while the other 5 patients had only
      transitory ischaemic attacks with hemiparesis or transitory aphasia. The lesions
      were revealed by means of duplex system echotomography (Aloka-Hellige Model SSD
      630) and spectral analysis of Doppler signal (Vasoscan-Sonicaid) and they were
      confirmed later by bilateral carotid arteriography in all patients. The
      intracranial circulation was also followed up by non-invasive methods, making use
      of spectral-analysis of the Doppler signal with pulsed wave on TC-2 64-B
      apparatus. The cases studied by us, which present pathogenic situations more
      rarely encountered, have shown that none of them observed a 'mathematical model'
      of compensation of blood flow (BF). More exactly, 2 patients with the same type
      of lesions and topography did not have a unique model of compensation of BF. It
      seems that both the possibilities of individual self-regulation of cerebral BF
      and the extracerebral factors, especially those belonging to cardiac activity,
      are decisive in the compensatory activity of cerebral circulation, while the
      modalities in which this is accomplished depend chiefly upon the functional
      condition of the collateral arteries as a whole.

PMID- 1355875
TI  - Haemodilution in acute ischaemic stroke comparison of two haemodilution regimen.
AB  - In a prospective study we randomly allocated 50 patients with acute ischaemic
      stroke in the area of the middle cerebral artery within 12 hours after onset to
      two moderate hypervolemic haemodilution regimen consisting of 500 ml of 10%
      hydroxyethyl starch per day for 10 days. In the high haematocrit group the target
      haematocrit of 41-42% was achieved by 0-3 phlebotomies and additional replacement
      of that volume with the colloid in 3 days. In the low haematocrit group with 1-4
      phlebotomies a target haematocrit of 37-38% was reached in 4 days. The groups did
      not differ regarding age, risk factors, haematocrit and neurological score. The
      improvement of the disturbed blood rheology was more pronounced in the low
      haematocrit group. One death occurred in each group. The neurological score
      showed a significantly greater increase in the low haematocrit group with +59% at
      day 5 and +125% at day 11; the data for the high haematocrit group were +34% and
      +89% respectively. We calculated a correlation (r = 0.36, p less than 0.02)
      between the rise in neurological score and the reduction of haematocrit. Our data
      suggest but not do prove that an early start on moderate hypervolemic
      haemodilution is beneficial in patients with acute ischaemic stroke and disturbed
      blood rheology.

PMID- 1355876
TI  - Carotid percutaneous angioplasty.
AB  - Clinical benefit from treatment of symptomatic severe carotid stenoses has been
      demonstrated recently. The safety profile of endarterectomy, however, justifies
      the development of alternative techniques as percutaneous transluminal
      angioplasty (PTA), at least in mild to moderate stenoses. Early results and
      follow-up data from our series of 44 carotid stenoses treated by PTA are reviewed
      in this paper, in comparison with other reports from literature. PTA may be
      beneficial as a therapy of symptomatic internal carotid stenoses, provided its
      cost/effectiveness has been evaluated by a valid method.

PMID- 1355877
TI  - Balloon angioplasty for cerebrovascular disease.
AB  - Percutaneous transluminal angioplasty (PTA) has become an established treatment
      for peripheral, renal and coronary vascular disease, where the success rate
      approaches 90% with complications occurring in less than 5% of patients. There
      has been a reluctance to recommend PTA of the internal carotid artery (ICA)
      because of concern about the risks of cerebral embolism. However, there are now a
      number of reports of technically successful PTA for ICA stenosis, as well as
      stenosis of other brachiocephalic arteries, demonstrating an improvement in
      vessel diameter and contour. Complications to date include transient neurological
      symptoms, asymptomatic carotid dissection and arterial spasm, but the risk of
      permanent stroke seems to be relatively low. The risks of embolization may be
      reduced by anticoagulation and avoiding arteries with obvious thrombus or
      ulceration. Current technical difficulties are likely to be surmounted by
      improvements in catheter design. PTA is most suitable for smooth ICA stenosis
      causing haemodynamic symptoms, fibromuscular dysplasia, surgically inaccessible
      stenosis, and patients with medical risk factors increasing the risks of carotid
      endarterectomy, such as ischaemic heart disease. Only brief admission is
      required, avoiding the surgical and anaesthetic risks of carotid endarterectomy.
      The preliminary results are encouraging enough to set up a randomized trial to
      determine the risks and benefits. It remains to be seen whether alterations in
      the calibre or contour of the vessel wall will reduce subsequent stroke. Whether
      cerebrovascular PTA will enter general use will depend on the balance of the risk
      benefit equation.

PMID- 1355878
TI  - Local thrombolytic therapy for thromboembolic occlusion of the middle cerebral
      artery.
AB  - We report on 10 patients with thromboembolic occlusion of the middle cerebral
      artery (MCA) who underwent local thrombolytic therapy. Six patients developed a
      MCA occlusion during long-standing interventional neuroradiological procedures,
      while four had a proven or suspected cardio-embolic stroke. Streptokinase or
      urokinase was applied by a microcatheter placed into the thrombus within six
      hours of clinical onset. Complete or partial revascularization was achieved in
      all patients. Recovery was complete in seven and partial in three of the
      patients. In two patients, minor haemorrhagic transformation of the infarct
      occurred, which did not lead to neurological deterioration. It is concluded that
      in a selected group of patients with MCA occlusion, local thrombolytic therapy
      represents a safe and effective therapy.

PMID- 1355880
TI  - Hypervolemic haemodilution and completed stroke: how important is the application
      time for its effect?
AB  - In 75 patients with completed stroke hypervolemic haemodilution was performed for
      1 day with 500 ml 6% HES 200.000/0.6-0.66 (Elohast) to test the acute influence
      of application time for haemorheological changes. The patients were divided into
      3 groups randomly selected: group A received the infusion for 2 hours, group B
      for 4 hours and group C for 6 hours. Haematocrit (HCT), whole blood viscosity (VI
      VB), blood elasticity (EL-VB) and plasma viscosity (VI-PL) were determined before
      onset of infusion, after 6 and 18 hours subsequently. The values obtained were
      compared with the onset results. In all groups and parameters after 6 hours there
      was a significant decrease. After 18 hours group A showed a significant higher
      value of HCT and increasing trends for VI-VB and EL-VB. In group B after 18 hours
      a significant decrease of VI-VB could be observed. In group C all values remained
      significantly below the onset. The results show, that one important
      haemorheological argument for an effective form of haemodilution should also be a
      long application time. This might be one of the reasons, why in some studies with
      hypervolemic haemodilution no positive results could be obtained.

PMID- 1355879
TI  - Influence of haemorrhagic transformation on the outcome of thrombolytic therapy
      for patients with acute brain embolism.

PMID- 1355881
TI  - Vertebro-basilar ischaemic disease: one or more entities? 460 cases.

PMID- 1355882
TI  - Aged but not young rats develop metabolic, memory deficits after chronic brain
      ischaemia.

PMID- 1355883
TI  - Implication of the polyamines in the neurotoxic effects of N-methyl-D-aspartate.
AB  - N-Methyl-D-aspartate (NMDA) receptor activation selectively releases the
      polyamines spermine and spermidine from the rat striatum in vivo. The
      intrastriatal injection of spermine or spermidine is neurotoxic, but this
      toxicity is not blocked by MK-801 and unlikely to be mediated via the NMDA
      receptor. The neurotoxic effects of intrastriatally injected NMDA can, however,
      be reduced by polyamine synthesis inhibition with difluoromethylornithine.
      Alterations in polyamine metabolism in the ischaemic brain, although perhaps
      induced by NMDA receptor activation, may contribute to ischaemic cell loss via
      NMDA-independent mechanisms, possibly related to the diverse effects of
      polyamines on calcium homoeostasis and channel function.

PMID- 1355884
TI  - Metabolic derangement in viable periinfarct tissue in the course of acute
      ischaemic infarction: a multitracer positron emission tomography (PET) study.
AB  - We used a multitracer positron emission tomography (PET) approach to assess
      metabolic changes in infarcted and periinfarct tissue in acute ischaemic stroke.
      16 patients were studied within 6-48 hours (mean, 23 h) after onset of symptoms
      from a first hemispheric stroke and again 13-25 days later (mean, 15.6 days).
      Regional cerebral metabolic rates of oxygen (CMRO2) and glucose (CMRGlc), blood
      flow (CBF) and blood volume (CBV) were measured and oxygen extraction (OEF) as
      well as glucose extraction (GEF) and microvascular transit time were calculated.
      PET images were three-dimensionally aligned using serial CT or MRI scans. Regions
      of interest on the side of the infarction were individually compared to
      contralateral mirror regions. In the infarction core CBF, CMRO2 and CMRGlc were
      significantly lower than on the contralateral side and did not change during
      time. In the periinfarct regions there was a decreased CMRO2 with progressive
      deterioration over time while CBF slightly increased. Only in a few ischaemic
      regions with initially increased OEF oxygen metabolism was preserved during the
      course of time.

PMID- 1355885
TI  - Production of transient ischaemic events by platelet emboli in baboons.
AB  - To investigate the pathophysiological process of transient ischaemic events in a
      clinically relevant model, we produced transient focal cerebral ischaemia in five
      baboons using endogenously generated platelet microemboli. Thrombogenic segments
      of Dacron vascular graft were incorporated as unilateral carotid arterio-arterial
      shunts to produce endogenous platelet microemboli. The embolized microparticles
      were quantified by isotopic imaging using 111In-platelets and by transcranial
      Doppler ultrasonography. Platelet microemboli accumulated rapidly in the shunted
      carotid territory and reached a maximum value of 3.2 +/- 0.8 x 10(9) in the
      embolized hemisphere 20 min after initiating blood flow through the graft
      segment. Sixty min after removing the grafts 111In-platelets were largely cleared
      from hemispheric vasculature. Recovered animals exhibited mild contralateral
      hemiparesis which disappeared completely within 24 h. We conclude that
      endogenously generated platelet microemboli accumulate transiently in the
      dependent cerebral circulation and produce corresponding transient focal
      neurological dysfunction. This model may be useful in the evaluation of new
      therapeutic strategies in acute stroke.

PMID- 1355886
TI  - Molecular biological studies in atherothrombotic brain infarction.
AB  - Strokes due to atherosclerosis are the most prominent neurological disease
      affecting adults, and efforts to reduce stroke occurrence, in addition to stroke
      risk reduction, will require insights into molecular mechanisms. Our studies
      showing abnormal metabolism of low and high density lipoproteins (LDL and HDL) in
      vivo and of RFLP in apoprotein AI, the major protein of HDL, in stroke-prone
      subjects suggest that greater exploration of fundamental mechanisms of
      atherothrombotic brain infarction (ABI) should yield preventative strategies, the
      ultimate treatment for strokes.

PMID- 1355887
TI  - Quantitative middle cerebral artery flow in normal and vasospastic arteries.
AB  - To determine the degree of MCA vasospasm necessary to exceed the ischaemic
      threshold of blood flow reduction to less than 1/3 normal flow, we developed a
      computer model of blood flow in the middle cerebral artery distribution. When
      solved for a 3 mm trunk diameter, it showed a normal flow of 179 ml/min. It was
      necessary to decrease trunk diameter by 75%, or branch diameter by 50%, or
      increase peripheral resistance by a factor of 3, in order to decrease blood flow
      to less than 1/3 normal.

PMID- 1355888
TI  - Effect of circulating pattern and complicating factors on outcome for ruptured
      anterior communicating artery aneurysms.
AB  - We reviewed outcome for ruptured anterior communicating artery (ACoA) aneurysm in
      40 patients and attempted to establish its relationships with circulating pattern
      and complicating factors. Circulation Type-1 and Type-2 were associated with a
      better outcome than Type-3 and Type-4. Apart from arterial hypertension and
      cerebral infarction, all the complicating factors, i.e., vasospasm, brain oedema,
      intraparenchymal and/or intraventricular haemorrhage and hydrocephalus were
      related with an increased risk for poor outcome, but the broad outcome was more
      depended on circulating pattern for anterior cerebral territories.

PMID- 1355889
TI  - Stroke and dolichoectatic intracranial arteries.
AB  - During a 6-year-period, in 45 patients the diagnosis of dolichoectatic
      intracranial arteries was established. Dolichoectasia of the vertebrobasilar
      system was the most frequent finding (n = 39). Twenty-two patients presented with
      brain stem ischaemia, and 10 patients had ischaemic hemispheric events. Six
      patients had symptoms due to compression of cranial nerves. Hydrocephalus was
      observed once. Peak and mean flow velocities in 39 patients with dolichoectatic
      basilar arteries as revealed by transcranial Doppler ultrasound were
      significantly reduced (p less than 0.00001) when compared with an age-adjusted
      control group of 20 patients without evidence of vertebrobasilar dolichoectasia
      on angiogram. Non-invasive MR-angiography offered an excellent imaging of the
      vascular abnormality. The combined use of CT, TCD, MRI and MR-angiography allows
      reliable non-invasive diagnosis of dolichoectatic intracranial arteries. This
      condition seems to play an underestimated role in stroke patients, in particular
      with respect to the vertebrobasilar circulation.

PMID- 1355890
TI  - Supergiant anterior circulation aneurysms.
AB  - Six cases of very large anterior circulation intracranial aneurysms are
      presented. Aneurysms of 53-84 mm in three female and two male adults and a 40 mm
      lesion in a seven week infant were successfully excised. Three patients tolerated
      trial intraluminal balloon occlusion preoperatively and underwent subsequent
      parent artery ligation and aneurysmectomy with gratifying outcome. Three patients
      failed to tolerate trial occlusion and underwent prophylactic saphenous vein
      bypass grafts from the common carotid artery to the middle cerebral (MCA) prior
      to aneurysmectomy. In two of these (a 72 mm MCA and a 84 mm petrous carotid
      aneurysm), severe brain swelling after successful bypass procedures necessitated
      emergency craniotomy for aneurysmectomy and decompression. One of these never
      recovered and died one month later. In both cases in which malignant brain
      swelling followed bypass, preoperative CT and MR revealed significant hemispheric
      oedema and shift. Both patients had presented with signs of increased
      intracranial pressure and global mentational difficulties. Supergiant
      intracranial aneurysms pose major therapeutic risks, alternative therapeutic
      avenues must be addressed.

PMID- 1355891
TI  - Haemodynamic changes following carotid occlusion: MRI angiography and
      transcranial Doppler patterns.
AB  - To see the signal changes in MR angiography (MRA) when occlusions or severe
      stenoses of carotid arteries occur and to relate these data with the velocity
      values provided by transcranial Doppler sonography (TCD), 20 patients showing
      symptomatic or asymptomatic unilateral carotid obstructions underwent both MRA
      and TCD after digital angiography investigation. No MRA signal was recorded
      immediately downstream from the carotid occlusion. Low flow velocity values in
      the carotid siphon and middle cerebral artery (MCA) ipsilateral to the carotid
      obstruction were associated with altered MRA signals corresponding to the same
      vessels. Turbulence phenomena induced by reversed flow in the anterior cerebral
      artery induced MRA signal impairments. In carotid occlusions, there may be a
      relationship between the MRA patterns and the flow velocity variations detected
      by TCD, but the two approaches have to be applied together since they provide
      complementary information.

PMID- 1355893
TI  - Papers presented at the 1st International Conference on Stroke. Geneva,
      Switzerland, May 30-June 1, 1991.

PMID- 1355892
TI  - Correlation of MRI and CT data with outcome of cerebral revascularization after
      stroke.
AB  - Sixteen patients with the occlusion of the internal carotid artery (ICA)
      underwent extra-intracranial bypass surgery. All patients had stroke in evolution
      or completed stroke with mild or moderate (n = 9) or severe (n = 7) neurological
      deficits. In each case, the clinical course, magnetic resonance imaging (MRI),
      computed tomography (CT) and angiographic (AG) findings were evaluated. Patients
      were followed up from 9 months to 2.5 years postoperatively. MRI was much more
      sensitive than CT for appreciating the ischaemic tissue. The infarct volume
      determined by MRI had greater extent than previously detected by CT. If the
      difference of the infarct volume, detected by MRI and CT was more than 30% the
      patients appeared to have benefited from bypass surgery as demonstrated
      clinically as well as with postoperative MRI and AG studies. Patients with lesser
      difference showed insignificant or no postoperative improvement.

PMID- 1355895
TI  - Hyperhomocysteinemia as a risk factor for stroke.

PMID- 1355894
TI  - Correlation between serum lipids and stroke in an Israeli population.
AB  - The role of blood lipids as a risk factor for cerebrovascular disease remains
      uncertain. In the present prospective study, 202 patients admitted with stroke to
      a community hospital in Jerusalem were evaluated. All patients had a full
      clinical and neurological evaluation, and a risk factor analysis. The study
      protocol included routine blood evaluation, fasting blood lipid analysis, brain
      imaging, 2D echocardiography and carotid Doppler ultrasonography. Stroke risk
      factors were correlated to stroke types as defined by the modified NINCDS Stroke
      Data Bank Criteria. Lacunar and atherosclerotic ischaemic infarctions were the
      most frequent type of stroke in both sexes. Lipid values were in general lower in
      males than in females. Comparison of stroke patients to age and sex matched
      controls disclosed lower LDL-C values in male and female patients (p less than
      0.001), and lower cholesterol levels in women with strokes than in control
      subjects (p less than 0.001). Our study corroborates previously reported risk
      factors for stroke: hypertension (major risk factor in both sexes), smoking (more
      prevalent in males) and diabetes (more frequent in females).

PMID- 1355896
TI  - Flow separation in the carotid bulb: prognostic significance.
AB  - It has been previously shown that boundary layer or flow separation occurring in
      the carotid bulb and detected by duplex scanning denotes minimal or no carotid
      atherosclerotic disease as demonstrated by angiography and reliably predicts
      aetiology other than carotid artery disease in symptomatic patients. To evaluate
      outcome at long-term follow-up we prospectively studied 94 patients (48 males, 46
      females) who demonstrated bilateral flow separation. Mean age was 61.2 years (27
      to 86 years). Mean follow-up was 57 months (5 to 113 months). There was one death
      during follow-up at 69 months. It was stroke related. Using age and sex specific
      death rates for the general population 14.3 deaths would be expected for the same
      average period. By life table analysis, survival was 98.7% at five years compared
      to a general population expected 5 year survival of 85.9%. There were no strokes
      at 5 years of follow-up. (Age and sex specific stroke-free survival for
      Rochester, MN 1970-1974 is 98% at 5 years). TIA-free survival was 99% at one year
      (n = 87) and 96% at five years (n = 46). It is concluded that the presence of
      boundary layer separation in the carotid bulb not only indicates absent or
      minimal atherosclerotic disease, but is predictive of a favourable long-term
      outcome with respect to mortality and neurological events.

PMID- 1355897
TI  - Frequency of transient ischaemic attacks in strokes: place for a preventive
      treatment.
AB  - Transient ischaemic attack (TIA) represents a neurological deficit during less
      than 24 hours, without any abnormality on CT scan. This symptom may have 2 risks:
      it may give place to a severe stroke, and it is not always linked to an ischaemic
      mechanism. This work rests on a population-based registry existing in Dijon since
      1985 with a specific and exhaustive registration. CT scan allows the mechanisms
      of stroke to be identified: cortical infarct, lacunar infarct, cerebral
      haemorrhage, and TIA. TIA represent 15% of stroke. Survival rate of 80% is better
      than other strokes. A TIA may appear before a cerebral infarct in 48% of the
      cases, a lacunar infarct in 18% of the cases, another TIA in 28% of the cases,
      and a haematoma in 8% of the cases. Therefore TIA is an important symptom
      appearing before severe stroke, that may let place to a preventative action.

PMID- 1355898
TI  - Haemorheological factors in the pathophysiology of acute stroke.
AB  - Blood viscosity studies were carried out in fourteen patients with acute stroke,
      eight with cerebral infarction, six with cerebral haemorrhage and in thirteen
      controls. We observed a statistically significant higher values of plasma, red
      cell and whole viscosity in patients with acute stroke than in normal controls.
      Plasma fibrinogen levels were statistically higher (p less than 0.01) in patients
      than in normal controls. The platelet aggregation was increased in two young
      adults with acute stroke. The results suggest that the haemorheological factors
      play an important role in the pathophysiology of stroke patients.

PMID- 1355899
TI  - Effect of the risk factors for stroke on survival.
AB  - In a case-controlled study into the risk factors for admission to hospital with
      stroke, 400 subjects and 400 age and sex-matched controls were recruited. All bar
      two subjects were followed until death or 6 months. Previous stroke and regular
      snoring (p = 0.0013 and p less than 0.0001 respectively) were the only two risk
      factors adversely to effect mortality. Transient ischaemic attack, ischaemic
      heart disease, hypertension, atrial fibrillation, diabetes mellitus did not
      significantly effect prognosis. An apparent beneficial effect of drinking alcohol
      and smoking became insignificant when the confounding influence of age was taken
      into account.

PMID- 1355900
TI  - Watershed cerebral infarcts: retrospective study of 24 cases.
AB  - Twenty-four patients presenting an acute stroke with watershed cerebral infarct
      on CT scan or MRI were included in this retrospective study. Age was 63 +/- 14
      years (mean +/- SD), and sex ratio was 2 men for 1 woman. Main clinical features
      were: in anterior location, lower limb weakness and frontal syndrome with
      transcortical motor aphasia in left lesions or spatial dyscalculia in right ones;
      in posterior location, brachiofacial weakness with constant quadranopsia and
      hypoesthesia, and Gerstmann syndrome in left lesion. There was no distinctive
      feature for subcortical and multiple infarcts. In bilateral infarcts, there were
      one pseudobulbar syndrome, and 2 pseudo brainstem syndromes with
      neuropsychological signs. Aetiologies were severe carotid artery disease in 14
      cases, severe cardiopathy in 6, isolated cerebral angiitis in 1, essential
      thrombocythemia in 1, protein C deficiency with sickle cell disease in 1, and
      cholesterol emboli in 1 anatomical case. CBF performed in carotid artery
      occlusions or tight stenoses showed evidence of haemodynamic changes.
      Microembolic process can be proposed in the case with cholesterol emboli.
      Preventive treatment is discussed.

PMID- 1355901
TI  - Participation of arginine vasopressin-mediated and adrenergic system-mediated
      mechanisms in the hypertension induced by intracerebroventricular administration
      of NMDA in freely moving rats.
AB  - Effects of intracerebroventricular (third ventricle) injection of N-methyl-D
      aspartate (NMDA) on arterial blood pressure, on heart rate, on arginine
      vasopressin (AVP) and levels of catecholamines in plasma and on the behaviour of
      normotensive freely-moving rats have been evaluated. N-Methyl-D-aspartate
      significantly (P less than 0.01) increased arterial blood pressure and levels of
      catecholamines and AVP in plasma. With 0.1-1.0 micrograms/rat all animals
      presented psychomotor agitation, stereotyped movements, hyperexcitability,
      exophthalmus, dyspnoea, jumping, rearing and teething. The selective antagonist
      for NMDA receptors, 2-APV injected in the third ventricle, significantly (P less
      than 0.01) antagonized the hypertension, the increase in levels of catecholamines
      and AVP in plasma and behavioural effects. An antagonist of alpha 1 adrenergic
      receptors, prazosin (i.v.), an agonist of alpha 2 adrenergic receptors, clonidine
      (i.c.v.) and a relatively selective antagonist of V1 subtype of receptor of AVP,
      CGP 25838 (i.c.v. and i.v.), 15 min before NMDA, significantly (P less than 0.01)
      decreased the effects induced by the injections of NMDA. On the contrary, an
      antagonist of opiate receptors, naloxone (i.v.), 15 min before NMDA,
      significantly (P less than 0.01) increased the NMDA-induced modifications.
      Pretreatment with the antagonists at these doses, did not significantly modify
      the basal values of arterial blood pressure and behaviour. Only 2-APV sometimes
      induced ataxia, lasting about 5 min. This study points out an increase in the
      central sympathetic efferent activity and in release of AVP involved in the NMDA
      induced cardiovascular and behavioural effects.

PMID- 1355902
TI  - [Multidrug resistance (MDR) to cytostatics in proliferative diseases of the
      hematopoietic system].

PMID- 1355903
TI  - [Beta 2 agonists and the course of bronchial asthma].

PMID- 1355904
TI  - Detection of prodynorphin end products in lizard, turtle, and alligator brain
      extracts.
AB  - Heterologous radioimmunoassays (RIAs) for the mammalian prodynorphin end
      products, alpha-neo-endorphin, dynorphin A(1-17), dynorphin A(1-8), and dynorphin
      B(1-13) were used to screen brain extracts obtained from representatives of the
      major surviving orders of reptiles: Chelonia (Pseudemys scripta), Squamata
      (Anolis carolinensis), and Crocodylia (Alligator mississippiensis). Methanol/acid
      extracts of whole brains obtained from each species were separately fractionated
      by gel filtration chromatography and reversed-phase HPLC. In all three species,
      an immunoreactive form of alpha-neo-endorphin was detected with the same
      retention time as synthetic mammalian alpha-neo-endorphin following reversed
      phase HPLC analysis. In all three species, reversed-phase HPLC analysis revealed
      a novel form of dynorphin B(1-13)-related immunoreactivity. With the available
      immunological probes, dynorphin A products were only detected in the Anolis brain
      extracts. Both dynorphin A(1-17) and dynorphin A(1-8) were detected in this
      species.

PMID- 1355905
TI  - Oral administration of Tyr-MIF-1 stimulates gastric emptying and gastrointestinal
      motility in rodents.
AB  - The effects of orally administered Tyr-MIF-1, an agonist of an endogenous
      antiopiate system, were examined on gastric emptying in mice and gastrointestinal
      myoelectric activity in rats. Tyr-MIF-1 (5 mg/kg in mice, 20 mg/kg in rats)
      accelerated gastric emptying of a methylcellulose test meal, increased the
      frequency of antral spike bursts, and disrupted intestinal migrating myoelectric
      complexes. These effects were reproduced by a subcutaneous administration of Tyr
      MIF-1 at the same dosage. They were blocked by naloxone (1 mg/kg) but not by the
      kappa receptor subtype antagonist MR 2266 (1 mg/kg). The GABAA antagonist
      bicuculline (0.5 mg/kg), but not the GABAB antagonist 2-hydroxysaclofen (4
      mg/kg), also antagonized the effects of Tyr-MIF-1. These data demonstrate that
      oral Tyr-MIF-1 stimulates gastric emptying and gastrointestinal motility through
      a systemic or central action that involves opioid and GABA systems.

PMID- 1355906
TI  - Chrononephrotoxicity in rat of a vancomycin and gentamicin combination.
AB  - The effect of time of administration on excretion of two brush border enzymes-
      alanine aminopeptidase (AAP) and gamma-glutamyl transferase (gamma GT), and a
      lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG) with a single high dose
      of vancomycin, gentamicin or a combination of vancomycin and gentamicin was
      studied in male Wistar rats and compared with elimination of a control group. The
      rats received vancomycin intraperitoneally (200 mg.kg-1), gentamicin
      intramuscularly (100 mg.kg-1) or the combination of the drugs by the same route.
      A control group received isotonic NaCl solution. The four groups of animals
      received a single injection at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. and urine
      excretion values for AAP, gamma GT and NAG were determined 24 hr later. The
      results show that the nephrotoxicity of gentamicin + vancomycin is greater than
      that observed with gentamicin, which again is greater than that observed with
      vancomycin. Furthermore, circadian variations in renal toxicity were observed,
      the least occurring at 8 a.m.

PMID- 1355907
TI  - A broad-spectrum cytolytic toxin from Bacillus thuringiensis var. kyushuensis.
AB  - Bacillus thuringiensis (Bt) var. kyushuensis synthesizes a mosquitocidal
      crystalline inclusion containing several proteins ranging from 140 to 14 kDa. We
      have identified a 25 kDa protein protoxin in this inclusion which is not
      cytolytic, but when activated proteolytically to 23-22 kDa products is cytolytic
      to mosquito, lepidopteran and mammalian cells, can release entrapped glucose from
      liposomes and forms cation-selective channels in a planar lipid bilayer. This
      broad-spectrum cytolytic toxin is related antigenically to the 23 kDa toxin from
      Bt var. darmstadiensis strain 73-E10-2, but not to the 25 kDa CytA toxin of Bt
      var. israelensis. The cytolytic activity of these Bt var. kyushuensis toxins,
      like that of the latter two toxins, can be neutralized by incubation with
      liposomes containing phospholipids.

PMID- 1355908
TI  - The neurons in layer 1 of cat visual cortex.
AB  - We have examined the morphology of neurons in layer 1 by injecting them
      intracellularly with lucifer yellow in lightly fixed brain slices (250 microns
      thick) taken from the medial bank of area 17 in adult cats. Of 22 neurons with
      well-filled dendrites, 16 had smooth dendrites, two had sparsely spiny dendrites
      (less than 200 spines) and, unexpectedly, four had spiny dendrites typical of
      pyramidal cells. The axon was generally not well filled. Computer reconstructions
      showed that parts of the dendritic tree had been lost in the sectioning.
      Nevertheless, measurements of the length of intact dendrites suggested an average
      diameter of the dendritic tree of 220 microns. The density of the neurons was
      such that the dendritic trees of about six neurons cover each point in layer 1.
      Thus, despite the very low density of neurons that characterizes layer 1, there
      are more than sufficient neurons to sample from the entire representation of the
      visual field in area 17.

PMID- 1355909
TI  - A novel cholinergic receptor mediates inhibition of chick cochlear hair cells.
AB  - The central nervous system provides feedback regulation at several points within
      the peripheral auditory apparatus. One component of that feedback is inhibition
      of cochlear hair cells by release of acetylcholine (ACh) from efferent brainstem
      neurons. The mechanism of hair cell inhibition, and the character of the presumed
      cholinergic receptor, however, have eluded understanding. Both nicotinic and
      muscarinic, as well as some non-cholinergic ligands can affect the efferent
      action. We have made whole-cell, tight-seal recordings from short (outer) hair
      cells isolated from the chick's cochlea. These are the principal targets of
      cochlear efferents in birds. ACh hyperpolarizes short hair cells by opening a
      cation channel through which Ca2+ enters the cell and subsequently activates
      Ca(2+)-dependent K+ current (Fuchs & Murrow 1991, 1992). Both curare and atropine
      are effective-antagonists of cholinergic inhibition at 3 microM, whereas
      trimethaphan camsylate and strychnine block at 1 microM. The normally
      irreversible nicotinic antagonist, alpha-bungarotoxin, reversibly blocked the
      hair cell response, as did kappa-bungarotoxin. The half-blocking concentration
      for alpha-bungarotoxin was 26 nM. It is proposed that the hair cell AChR is a
      ligand-gated cation channel related to the nicotinic receptor of nerve and
      muscle.

PMID- 1355910
TI  - Costs to host defence and the persistence of parasitic cuckoos.
AB  - Raising genetically unrelated young is maladaptive, yet brood parasitism is
      widespread in birds. In several systems, hosts can evolve near-perfect defences
      against the parasite (discrimination and rejection of unlike eggs), making it
      difficult to understand how the parasite continues to exist. This study
      demonstrates costs to host defences (e.g. rejection of one's own eggs) such that
      once the parasite goes extinct on a particular host species, defence mechanisms
      are selectively disadvantageous. The consequent loss of host defences, and
      potential for re-exploitation of the host by the parasite, can explain the
      continued persistence of avian brood parasites. The results provide one general
      explanation for coexistence of parasites and their hosts.

PMID- 1355911
TI  - On the existence of 'fast' and 'slow' directionally sensitive motion detector
      neurons in insects.
AB  - In a fly, butterfly, locust and dragonfly we examined the responses of a variety
      of directional motion-sensitive neurons which run from the brain down the ventral
      cord. The stimulus was a sinusoidally modulated moving pattern of regular stripes
      presented at a range of velocities in random order for either 0.1 s or 2.0 s. The
      response was measured as the total number of spikes to each stimulus. The neurons
      fall into two groups, 'fast' and 'slow'. The responses of the fast type rise
      progressively to a peak contrast frequency at 15-20 Hz for all four insects, and
      decline at higher contrast frequencies. The responses of slow neurons rise
      rapidly to a peak at 1-10 Hz and then decline more slowly across the range where
      the fast neurons are at their peak. The existence of two groups of neurons with
      overlapping response ranges to different velocities of the same pattern,
      presented in exactly the same way, provides the insect with a means of measuring
      angular velocity irrespective of contrast, spatial frequency or intensity. As an
      input mechanism it is proposed that there are two types of unit motion detector,
      fast and slow, the latter being the main input to the optomotor system. It is
      also argued that even these inputs are not sufficient to provide a mechanism for
      the whole repertoire of normal insect vision.

PMID- 1355912
TI  - Intracellular symbionts and the evolution of uniparental cytoplasmic inheritance.
AB  - Uniparental inheritance of cytoplasmic elements is widespread among eukaryotic
      organisms and is achieved by a diverse range of mechanisms. This paper shows that
      the cytoplasmic genetic system would be expected to evolve towards uniparental
      inheritance, given the existence of deleterious symbionts capable of invading the
      host cytoplasm together with nuclear genes that lead to the elimination of
      cytoplasmic elements from one of the gamete types. The reason for this is that,
      under biparental inheritance, foreign symbionts with strong deleterious effects
      are able to spread through host populations. A nuclear modifier gene which leads
      to the loss of cytoplasmic elements from one gamete type gains a net advantage as
      a symbiont spreads, because the modifier sometimes gives rise to a symbiont-free
      zygote. Insofar as small gametes reduce the rate of symbiont transmission to the
      zygote, modifier genes causing small gamete size would tend to accumulate, so
      that cytoplasmic inheritance would become associated with maternal rather than
      paternal gametes. Once uniparental inheritance predominates in the host
      population, the population is protected from invasions by a large class of
      harmful symbionts, but at the same time those symbionts that benefit their hosts
      are still able to increase in frequency.

PMID- 1355914
TI  - Replication origins and pause sites in sea urchin mitochondrial DNA.
AB  - We have used a combination of one- and two-dimensional agarose gel
      electrophoresis, and solution hybridization to strand-specific probes, to map the
      replication origin of sea urchin mitochondrial DNA and to investigate the
      structure of replication intermediates. These assays are consistent with
      replication initiating unidirectionally from the D-loop region by D-loop
      expansion, as in vertebrates. A prominent site of initiation of lagging-strand
      synthesis lies at, or near to, the boundary between the genes for ATPase 6 and
      COIII, which is also close to a pause site for leading-strand synthesis. These
      findings suggest a role for pause sites in the regulation of mitochondrial
      transcription and replication, possibly involving template-binding proteins.

PMID- 1355913
TI  - Purification of HlyX, a potential regulator of haemolysin synthesis, and
      properties of HlyX:FNR hybrids.
AB  - The hlyX gene of the swine pathogen Actinobacillus pleuropneumoniae is homologous
      to FNR, an anaerobic transcriptional regulator of Escherichia coli. It endows a
      haemolytic phenotype upon E. coli, and will complement the anaerobic respiratory
      deficiencies of fnr mutants of E. coli. The coding region of the hlyX gene was
      expressed in E. coli and the HlyX protein was purified by using an assay based on
      its immunological cross-reactivity with anti-FNR antibodies. The HlyX protein had
      the predicted N-terminal sequence, and resembled the isolated FNR protein in size
      (Mr 29,000) and monomeric organization. It has no detectable haemolysin activity
      per se, and is therefore presumed to confer a haemolytic phenotype by activating
      a latent haemolysin gene in E. coli. Studies with gene fusions showed that HlyX,
      like FNR, can function as an anaerobic activator and repressor of FNR-regulated
      genes in vivo. Plasmids that express hybrid HlyX:FNR proteins in which the
      189/190-residue N-terminal segments and the remaining 50/60-residue C-terminal
      segments are exchanged, retained their FNR-specific functions but failed to
      confer a haemolytic phenotype. This suggests that the specificity for activating
      the haemolytic response requires the participation of unique features in both the
      N- and C-terminal segments of HlyX.

PMID- 1355915
TI  - Influence of the bathing medium on the contractile responses of the rabbit
      urinary bladder.
AB  - This study examined contractile responses of the in vitro rabbit whole-bladder
      preparation to field stimulation, bethanechol and KCl in Tyrode's solution and
      minimum essential medium (MEM). We found frequency-dependent increases in
      intravesical pressure in bladders incubated in Tyrode's solution and MEM.
      However, bladders incubated in MEM consistently responded with greater increases
      in intravesical pressure compared to those incubated in Tyrode's solution.
      Similarly, there were frequency-dependent increases in the rate of pressure
      generation in bladders incubated in Tyrode's solution and MEM, and bladders
      incubated in MEM responded with greater rates of pressure generation than those
      incubated in Tyrode's solution at frequencies of 1, 2 and 4 Hz. In addition,
      there were significant increases in intravesical pressure generated in response
      to administration of 500 mmol/l bethanechol and 186.4 mmol/l KCl in bladders
      incubated in MEM compared to Tyrode's solution but no changes in the rate of
      pressure generation. The influence of L-methionine, one of the constituents of
      MEM, on the responses of whole bladders to nerve stimulation was also
      investigated. L-methionine at concentrations of 0.1 and 1.0 mmol/l had no effects
      on the increase in intravesical pressure or rate of pressure generation following
      nerve stimulation. It is speculated that the increases in contractile
      responsiveness of bladders incubated in MEM are related to the combination of
      amino acids, vitamins and other constituents of the cell culture medium.

PMID- 1355916
TI  - The Croonian Lecture, 1992. The key role of the thymus in the body's defence
      strategies.
AB  - For centuries the thymus has remained a mysterious organ with largely unknown
      functions. The first demonstration of its crucial role in the development of the
      immune system was reported in 1961, when it was found that mice thymectomized at
      birth had poorly developed lymphoid tissues, impaired immune reactivities, and an
      inordinate susceptibility to develop infections. Although thymus lymphocytes were
      for a long time deemed immunoincompetent, it was shown in 1967 that they could
      respond to antigen by proliferating to give rise to a progeny of cells which did
      not secrete antibody (T cells), but which had a remarkable ability to induce bone
      marrow cells (B cells) to become antibody formers. This was the first unequivocal
      demonstration of a major division of labour among mammalian lymphocytes.
      Tremendous progress in our understanding of the function of the thymus and of the
      T cells derived from it followed. Distinct T cell subsets were characterized and
      shown to have an essential role in initiating and regulating a variety of immune
      responses. The ontogenetic events which occurred during their differentiation
      were mapped, and this allowed studies of the selection of the T cell repertoire.
      The major histocompatibility complex and associated peptides were shown to govern
      T cell selection and antigen activation, and the antigen-specific T cell receptor
      and the genes which code for it were characterized. Future studies should allow
      some insight into how to activate T cells more effectively for vaccination
      purposes, and how to switch them off to prevent autoimmune reactions and to
      induce tolerance to transplanted tissues.

PMID- 1355917
TI  - Central and peripheral effects of repeated stress and high NaCl diet on
      neuropeptide Y.
AB  - This study was performed to investigate the influence of repeated psychological
      stress alone or combined with high NaCl intake on the function of the sympathetic
      nervous system. In addition, NPY levels have been measured in brain regions of
      potential importance in the central regulation of stress responses (ventrolateral
      and dorsomedial medulla, paraventricular and arcuate nucleus of the hypothalamus,
      and frontal cortex). Normotensive Wistar rats received a standard diet alone or
      supplemented with NaCl. To accentuate differences in sodium balance, rats on the
      high NaCl diet (HNa) were uninephrectomized. Half the animals on each diet were
      subjected to chronic stress using daily sessions (1 h) of immobilization stress.
      After 12 days, plasma levels of neuropeptide Y (NPY), norepinephrine (NE), and
      epinephrine (E) were measured basally and in response to acute footshock stress.
      HNa intake or chronic stress alone did not significantly alter either basal or
      stimulated plasma levels of NPY. However, combining the treatments produced a
      significant interaction, increasing the NPY response to footshock by 31% compared
      to HNa alone (p = 0.039) and by 98% compared to stress alone (p less than 0.001).
      Chronic stress increased basal levels of NE and enhanced the response to
      subsequent acute stress: combining the treatments did not yield further
      increases. Plasma levels of E were not significantly affected by the treatments.
      In the brain, stress alone had no effect on the NPY levels in the structures
      studied. HNa intake induced a significant increase in NPY levels of the arcuate
      nucleus, and produced a significant interaction with stress in the dorsomedial
      medulla. In a supplementary experiment, to evaluate the role of the autonomic
      nervous system in plasma NPY responses, treatment with the ganglion blocker
      hexamethonium was shown to significantly attenuate stress-induced changes in NPY,
      NE, and E.

PMID- 1355918
TI  - Effects of brain natriuretic peptide-32 on the extinction of active avoidance
      behavior in rats. Transmitter-mediated action.
AB  - Three doses of porcine brain natriuretic peptide (pBNP-32) were tested in regards
      to the extinction of active avoidance behavior following injection into the
      lateral brain ventricle in rats. This peptide delayed the extinction of the
      active avoidance reflex in a dose-dependent manner. To clarify the involvement of
      transmitters in the action of the peptide, the animals were pretreated with
      different receptor blockers in doses that did not affect the behavior of the
      animals in this learning paradigm. Dopaminergic, cholinergic, and alpha- and beta
      adrenergic blockers effectively blocked the delaying action of pBNP-32, whereas
      GABAergic, serotoninergic, and opiateergic blockers were ineffective. The data
      suggest that the delaying action of pBNP-32 on the extinction of active avoidance
      behavior is mediated via dopaminergic and alpha- and beta-adrenergic
      neuromediations.

PMID- 1355919
TI  - Neuroendocrine and behavioral responses during conditioned active and passive
      behavior in the defensive burying/probe avoidance paradigm: effects of
      ipsapirone.
AB  - Plasma epinephrine (E), norepinephrine (NE), and corticosterone (CORT)
      concentrations were determined in the rat before, during, and after a 15-min
      exposure to a nonelectrified probe on day after receiving electric shock (1.5 mA)
      through a probe mounted on the wall of the home cage. Rats displayed burying
      (active coping) if sawdust was provided on the floor and immobility (passive
      coping) if bedding was absent both during training and testing. The conditioned
      burying was accompanied by high plasma NE but low E and CORT concentrations,
      whereas immobility was associated with high CORT and low NE levels. A forced
      switch from the active to passive coping (training with and testing without
      sawdust) led to the highest rise in E concentration. The 5-HT1A agonist
      ipsapirone, with anxiolytic properties, dose-dependently (0.5 and 2.5 mg/kg, IV)
      reduced defensive burying behavior and increased the amount of time spent on
      feeding behavior in the presence of bedding material. Both plasma E and CORT
      levels were further elevated by the higher dose of ipsapirone. In the absence of
      bedding material, ipsapirone failed to affect immobility behavior, but it dose
      dependently elevated the stress-induced increase in E, NE, and CORT
      concentrations. Accordingly, the behavioral anxiolytic action of the 5-HT1A
      agonist ipsapirone was restricted to active coping, whereas neuroendocrine
      activation by the drug was present in all conditions. It is suggested that the
      effects of ipsapirone on behavioral coping and neuroendocrine regulation are
      produced by different populations of 5-HT1A receptors in the brain.

PMID- 1355920
TI  - Psychopharmacological responsiveness to the dopamine agonist quinpirole in normal
      weanlings and in weanling offspring exposed gestationally to cocaine.
AB  - The behavioral responsiveness to challenge doses of the D2 agonist quinpirole was
      examined in 21-day-old normal offspring (experiment 1) as well as offspring
      exposed gestationally to cocaine (experiment 2). In both experiments weanling
      rats received a subcutaneous injection of 0 (0.9% saline), 0.04, 0.08, 0.5, or
      1.0 mg/kg/3 cc of the D2 agonist quinpirole and were placed in a divided glass
      testing apparatus containing either a dish of wet mash plus a food pellet or wood
      block (experiment 1) or both a food pellet and a wood block (experiment 2).
      Behaviors were recorded for 5 min via time-sampling at 30 and 60 min post
      injection. In experiment 1 the three highest doses of quinpirole increased the
      amount of forward locomotion, rearing, sniffing and probing, as well as
      increasing directed oral movements at both the wood block and food pellet; in
      general these findings are reminiscent of those reported previously in adult
      animals. In experiment 2, cocaine-exposed weanlings exhibited an increased
      sensitivity to the stimulating effects of a low dose of the D2 agonist for
      forward locomotion and rearing as well as an increase in the overall incidence of
      sniffing behavior and chewing on food pellets. These data provide
      psychopharmacological evidence that the increase in striatal D2 binding
      previously observed in weanling offspring exposed gestationally to cocaine
      (Scalzo et al. 1990) may be associated with an increased behavioral sensitivity
      to the D2 agonist quinpirole.

PMID- 1355921
TI  - Chronic infusion of clonidine does not alleviate spontaneous morphine withdrawal
      symptoms in rats.
AB  - Opiate withdrawal is associated with behavioural symptoms and a sympathetic
      hyperactivity, the latter being sensitive to clonidine. The central question is
      whether behavioural symptoms would be also sensitive to clonidine. A rat model
      was used in which the locomotor activity was measured 24 h a day during the
      morphine withdrawal phase. Spontaneous withdrawal of morphine reduced strongly
      the high nocturnal locomotor activity, concomitantly decreasing food intake and
      body weight. Chronic infusion of clonidine (30-120 micrograms/kg/day) using
      osmotic minipumps had no effect on the withdrawal symptoms. Higher dosages (250
      1000 micrograms/kg/day) potentiated rather than alleviated the withdrawal
      symptoms, suggesting an alpha 1-adrenergic effect of clonidine rather than an
      alpha 2-action. Therefore, we studied the action of a more specific alpha 2
      agonist UK-14.304. UK-14.304 was less potent than clonidine in naive animals. It
      slightly alleviates the decrease of nocturnal activity during spontaneous
      morphine withdrawal. Furthermore, we have tested whether the effects of high
      dosages of clonidine could be altered by a specific alpha 1-antagonist
      doxazosine. Doxazosine reduced only slightly the potentiation in the decrease in
      food intake by clonidine during morphine withdrawal. For the other symptoms no
      interaction between doxazosine and clonidine was found. The data suggest that the
      use of clonidine in the detoxification of opiate dependent people is based on the
      suppression of the sympathetic hyperactivity rather than on symptoms with a more
      behavioural character.

PMID- 1355922
TI  - Effects of buspirone and gepirone on i.v. cocaine self-administration in rhesus
      monkeys.
AB  - Buspirone and gepirone were evaluated as potential pharmacotherapies for cocaine
      abuse by studying the effects of acute and repeated treatment on IV cocaine self
      administration in rhesus monkeys. Chlorpromazine was also evaluated as a positive
      control. Effects of IV drug pretreatments were tested during daily 60-min
      sessions with lever-pressing reinforced under a fixed-ratio 10 schedule of 0.02
      or 0.05 mg/kg cocaine infusions. Acute pretreatment with buspirone (0.1 and 0.3
      mg/kg, IV) increased rates of cocaine self-administration without disrupting food
      pellet consumption. Some doses of buspirone also produced changes in rates of
      cocaine self-administration without altering the within-session pattern of
      responding. In contrast, acute doses of gepirone had little effect on rates of
      cocaine self-administration, while disruptions in food consumption and changes in
      the within-session pattern of cocaine self-administration were obtained at the
      highest dose of gepirone tested (1.0 mg/kg). When either buspirone (0.1 and 0.3
      mg/kg, IV) or gepirone (0.1 mg/kg, IV) were administered daily for 10 days,
      consistent effects on cocaine self-administration were not observed. Thus, the
      effects of acute buspirone administration on cocaine-maintained behavior were
      similar to the effects produced by chlorpromazine and other dopaminergic
      antagonists, whereas, gepirone was ineffective. These results provide some
      support for further evaluation of buspirone as a potential pharmacotherapy for
      cocaine abuse, although its lack of efficacy with repeated treatment is not
      encouraging. The negative results with gepirone provide less rationale for
      continued investigations with this drug, possibly because of its lesser
      involvement than buspirone with dopaminergic neurotransmission.

PMID- 1355923
TI  - Dose-response relationship for oral idazoxan effects in healthy human subjects:
      comparison with oral yohimbine.
AB  - The effects of oral administration of the alpha 2 adrenergic receptor antagonists
      idazoxan (20 mg, 40 mg, 80 mg) and yohimbine (20 mg) were compared using a
      placebo-controlled within-subjects design. Healthy subjects completed 5 test days
      during which medication effects on mood and anxiety states, physiologic indices,
      plasma cortisol levels, and plasma levels of the norepinephrine metabolite 3
      methoxy-4-hydroxy-phenylethylene glycol (MHPG) were assessed. Idazoxan dose
      dependently increased plasma MHPG, plasma cortisol, systolic and diastolic blood
      pressure, and Panic Attack Symptom Scale scores in healthy subjects. Overall,
      yohimbine and idazoxan produced a similar pattern of behavioral and
      neuroendocrine responses. Since idazoxan possesses relatively greater receptor
      specificity compared to yohimbine, it may be a more useful alpha 2 antagonist in
      humans.

PMID- 1355924
TI  - Differences between antipsychotic drugs in persistence of brain levels and
      behavioral effects.
AB  - After a single dose of the butyrophenone neuroleptic haloperidol, behavioral
      effects and detectable drug levels in rat brain can last for several weeks. To
      determine if such persistence is a general property of neuroleptics, we compared
      drug levels and effects after IP administration of two butyrophenones
      (haloperidol and bromperidol), a high potency (fluphenazine) and a low potency
      (chlorpromazine) phenothiazine. Drug levels in brain tissue were measured by high
      pressure liquid chromatography and behavioral effects monitored as inhibition of
      apomorphine-induced stereotypy. Estimated near terminal elimination half-lives (t
      1/2) from brain for acutely administered chlorpromazine (20 mg/kg) and
      fluphenazine (1 mg/kg) were 0.41 and 0.62 days, respectively, and neither drug
      was detectable after 4 days. Fluphenazine given daily for 5 days showed an only
      slightly slower elimination (t 1/2 = 1.1 days). In contrast, near-terminal
      elimination half-lives from brain for haloperidol and bromperidol (both at 1
      mg/kg, IP) were much longer (6.6 and 5.8 days, respectively), and each was
      detectable for 21 days after dosing. Inhibition of apomorphine-induced stereotypy
      correlated highly (r = 0.95) with brain levels of haloperidol. For fluphenazine,
      given once or repeatedly, early inhibition was replaced within 1 week by
      supersensitivity to apomorphine which persisted for up to 3 weeks. These
      findings, indicating marked differences in clearance and recovery times after
      dosing with butyrophenones and phenothiazines, have clear implications for
      studies of the effects of neuroleptic drugs in rats.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1355926
TI  - Laparoscopic urological surgery in children.

PMID- 1355925
TI  - Effects of acute and chronic desipramine treatment on somatostatin receptors in
      brain.
AB  - The effects of acute (5 mg/kg, IP twice daily for 2 days) and chronic (5 mg/kg IP
      twice daily for 21 days) administration of desipramine (DMI) on [125I]-Tyr11
      somatostatin binding sites in brain were examined. There was no change in
      [125I]Tyr11-somatostatin binding in membranes prepared from the frontal cortex,
      striatum, and hippocampus of rats acutely or chronically treated with DMI as
      compared to non treated animals. [125I]Tyr11-somatostatin binding was increased
      in membranes prepared from the rat nucleus accumbens only after chronic DMI
      administration. Scatchard analysis of the binding data from the nucleus accumbens
      showed that [125I]Tyr11-somatostatin labels a single population of somatostatin
      binding sites with an affinity constant, Kd, of 1.8 +/- 0.60 nM and a Bmax of 330
      +/- 90 fmol/mg protein. Chronic treatment with DMI increased the Bmax (500 +/-
      140 fmol/mg protein) but had no effect on the Kd. This finding shows a regional
      effect of DMI on [125I]Tyr11-somatostatin binding sites in rat brain and suggests
      that somatostatin may play a role in the pathophysiology of depression.

PMID- 1355927
TI  - Treatment of ureteral calculi measuring 1 cm or greater in their largest
      dimension, using the pulsed-dye laser or extracorporeal shock-wave lithotripsy.

PMID- 1355928
TI  - Adulticidal effect of cyfluthrin against mosquitos of public health importance in
      Malaysia.
AB  - The efficacy of two formulations, wettable powder and emulsifiable concentrate,
      of cyfluthrin sprayed on plywood [10 mg (ai)/m2] was assessed against six species
      of mosquitos. The bioassay followed the WHO standard method, with some
      modification for the bioassay of insecticidal deposits on wall surfaces. The
      results indicated that these two formulations of cyfluthrin were effective
      against Anopheles dirus and Mansonia uniformis, moderately toxic to Aedes aegypti
      and Ae. albopictus in decreasing mortality through out the study period. It was
      least effective against Culex quinquefasciatus and An. maculatus, respectively.
      There was no statistically significant difference between these two formulations.

PMID- 1355929
TI  - Effectiveness of slow release formulations of fenthion (Baytex) in the control of
      Mansonia breeding in polluted pond habitats.
AB  - Effectiveness of two types of granular formulations of fenthion (Baytex) was
      evaluated in controlling the breeding of Mansonia mosquitos in polluted pond
      habitats. Calcium carbonate and sand granular formulations, when applied at 2.50
      g/m2 surface area with an average depth of 0.5 m were found to be effective in
      keeping the habitats completely free from Mansonia breeding for 14 days and 18
      days respectively. Release of insecticide was slow and the effective duration of
      control after a single application was relatively longer in the sand formulation
      when compared to the calcium carbonate formulation. Single application of calcium
      carbonate and sand granular formulations of fenthion could effectively prevent
      Mansonia adult emergence for 23 and 30 days, respectively in polluted pond
      habitats, without causing any adverse effect on non-target insects.

PMID- 1355931
TI  - Security for America's children: a report from the annual conference of the
      National Academy of Social Insurance (Part II).

PMID- 1355930
TI  - HTLV-I antibody study in normal individuals and unselected hospital patients in
      Malaysia.
AB  - A serological investigation for human T cell leukemia virus I (HTLV-I) infection
      was carried out at the University Hospital, Kuala Lumpur. A total of 626 sera
      from a non-patient population and 1,038 sera from unselected in-patients were
      screened for HTLV-I antibodies using an enzyme-linked immunosorbent assay
      (ELISA). 27/1664 (1.6%) were found to be reactive. However, on Western blotting,
      only 2 sera were confirmed positive, both showing reactions for the major core
      (p19 and p24) and the envelope (gp46) proteins. Both of the serum samples were
      from unselected hospital patients. Most of the remaining sera which were reactive
      on screening showed indeterminate results on Western blotting. These were further
      tested by radioimmunoprecipitation assay (RIPA) and none of these sera gave a
      positive reaction. Therefore, only 2/1038 (0.19%) unselected patients could be
      confirmed to have antibodies to HTLV-I. None of the normal individuals screened
      showed a positive Western blot result. Our data indicate that HTLV-I infection is
      present in our population, but at a low prevalence rate.

PMID- 1355932
TI  - [The use of emakor in arterial ischemia of the lower extremities in outpatient
      practice].
AB  - Overall 43 outpatients with arterial ischemia of the lower limbs were treated by
      emakor, a new Soviet drug that exerts a concomitant alpha- and beta-blocking
      action. The treatment resulted in a remarkable positive effect which manifested
      itself in amelioration of circulation in the lower limbs, positive time-course of
      changes in peripheral hemodynamics and in computer-aided tomography data. The use
      of emakor is contraindicated in exacerbation of gastrointestinal diseases,
      chronic pulmonary diseases associated with the obstructive syndrome, and marked
      signs of venous outflow obstruction in the lower limbs.

PMID- 1355933
TI  - [Peripheral thrombopenia secondary to proxibarbal therapy].

PMID- 1355934
TI  - alpha-Conotoxin GI produces tetanic fade at the rat neuromuscular junction.
AB  - The ability of the marine snail toxin, alpha-conotoxin GI, to produce blockade of
      singly evoked twitches and to produce tetanic and train-of-four fade has been
      determined in the isolated rat hemidiaphragm preparation. Results were compared
      to those obtained with a reversible (vecuronium) and an irreversible (alpha
      bungarotoxin) nicotinic acetylcholine antagonist and have been interpreted in
      terms of relative effects on post- and prejunctional nicotinic acetylcholine
      receptors at the neuromuscular junction. alpha-Conotoxin GI (0.5-2 microM)
      produced a concentration-dependent, readily reversible, decrease in the peak
      amplitude of single twitches and 50 Hz tetani, and an increase in tetanic and
      train-of-four fade. alpha-Conotoxin GI was consistently 2-3-fold more potent than
      vecuronium with respect to all of the measured tension parameters. Both alpha
      conotoxin GI and vecuronium were approximately 2-fold more potent in producing
      tetanic fade and in blocking tetanic contractions than in blocking single
      twitches. In contrast to both alpha-conotoxin GI and vecuronium, alpha
      bungarotoxin (0.13 microM) reduced the peak amplitude of both single twitches and
      50 Hz tetani to the same extent without the appearance of a large degree of
      tetanic or train-of-four fade. Based on a comparison of the in vitro time course
      of neuromuscular block and of the relative effects of vecuronium, alpha-conotoxin
      GI and alpha-bungarotoxin on twitches, tetani and trains-of-four, we conclude
      that alpha-conotoxin GI has both pre- and postjunctional activity at the
      neuromuscular junction. In this respect, alpha-conotoxin GI resembles the
      clinically used competitive neuromuscular blocking drugs rather than the
      irreversible snake alpha-neurotoxins.

PMID- 1355935
TI  - Different assays for HER-2/neu evaluation in breast cancer.
AB  - To evaluate different methodologic approaches for HER-2/neu analysis, we
      performed Southern, Northern, Western blot and histochemical assay on 112 samples
      from 86 primary tumors and 26 synchronous axillary metastatic lymph nodes of
      patients affected by operable breast cancer. Simultaneous statistical analysis of
      data obtained with the four methods (31 samples) showed that Western blot
      detected a higher percentage of alterations than the other assays (Cochran and
      Victor tests, 0.01 less than p less than 0.05). The same result was emphasized by
      pair analysis (McNemar, p less than 0.05), which evaluated the assay data two by
      two. Immunohistochemical evaluations were more in accord with immunoprecipitation
      data when performed on frozen or Bouin-fixed, paraffin-embedded tissues than on
      formalin-fixed, paraffin-embedded tissues.

PMID- 1355936
TI  - Laparoscopy for evaluation of cryptorchid testis.
AB  - Four male patients with a unilateral nonpalpable testis were considered for
      laparoscopy. Preoperative evaluation by computerized tomography and
      ultrasonography failed to demonstrate cryptorchid testis. Laparoscopy clearly
      identified the anatomy in all 4 cases. Two patients had an absent testis, 1
      patient underwent orchiectomy for a dysmorphic testis, and 1 patients underwent
      orchiopexy for a testis located within the inguinal canal. Pediatric laparoscopy
      is an effective and safe adjunct in the management of cryptorchid testis.

PMID- 1355937
TI  - [New, in Austria registered specialty drugs. Aknemycin 1% compositum. Hydrophilic
      ointment with color paste].

PMID- 1355939
TI  - WHO-NIH meeting on host cell selection of influenza virus variants. 13-14
      November 1991, National Institute for Biological Standards and Control,
      Hertfordshire, UK.

PMID- 1355938
TI  - [The antiepileptic system].

PMID- 1355941
TI  - ["Sluggish schizophrenia" (concerning the article by A.B. Smulevich and P.V.
      Mikhalev (S.S. Korsakov zhurnal nevropatologii i psikhiatrii, No. 12, l987, pp.
      186-187].

PMID- 1355940
TI  - [The mechanism of the intranasal action of dermorphin in representatives of 2
      classes of vertebrates].
AB  - It has been shown that endogenous opioid dermorphin induces effective analgesia
      after intranasal injection to fish (0.02-0.20 mg/kg) and rats (0.005 mg/kg).
      Maintenance of dermorphin analgesia after olfactory and trigeminal denervation
      indicates that the analgetic effect is not realized via the olfactory receptors
      or free terminals of the trigeminal nerve.

PMID- 1355942
TI  - [Changes in the biochemical composition of the cerebrospinal fluid in acute
      carbophos poisoning].
AB  - As far as the pathogenesis of poisonings with organophosphorus pesticides is
      concerned, in addition to irreversible inhibition of acetylcholinesterase (AGE)
      in tissues, of importance are changes in the other systems which essentially
      determine the outcome of intoxication. The purpose of the present study was to
      examine the nature of changes occurring in total protein and protein fractions,
      free amino acids (aspartic and glutamic acids, glycine, isoleucine, leucine) and
      in certain enzymes (AST, ALT, CP, GGTP, GDH) in the cerebrospinal fluid (CSF) of
      patients with acute Malathion insecticide poisoning. 137 patients aged 20 to 50
      years were placed under observation. There were 77 men and 60 women. 40 persons
      had poisoning of medium gravity and 97 were severely poisoned. The intake of the
      CSF was performed on days 1, 3, 10, 14 and 21 since the disease onset. It has
      been established that in acute Malathion insecticide poisoning, the CSF content
      of the stimulating mediator amino acids, aspartic and glutamic, rises within the
      early periods, whereas the concentration of the inhibitory mediator glycine
      decreases. The changes in protein fractions of the CSF are characterized by a
      fall of the content of globulins and a rise of albumins, thus attesting to the
      predominance of pathological processes in the brain, especially in the initial
      period of intoxication, and to the impairment of the blood-brain barrier. The
      development of intoxication is associated with activation in the CSF of LDN, CP,
      GGTP and GDH as well as by activation of LDH isozymes which is viewed as the
      result of the membranotoxic effect of a Malathion insecticide.

PMID- 1355943
TI  - [Effects of carnitine and cobamamide on the dynamics of mental work capacity in
      patients with anorexia nervosa].
AB  - The authors relate the results of studying intellectual work fitness in patients
      with anorexia nervosa (in the stage of cachexia) receiving the vitamin-like drugs
      carnitine and cobamamide. It has been shown that the long-term food deprivation
      leads to a reduction of intellectual work fitness, lability of productivity,
      fluctuations in the work quality, appearance of latent fatigue. In spite of the
      fact that standard nonspecific treatment ameliorates intellectual work fitness,
      it does not lead to its normalization. The use of carnitine and cobamamide in the
      course of nonspecific treatment results in the reduction of the time spent on
      task implementation, a rise of the work rate as compared to the control group.
      However, this does not fully remove latent fatigue and does not bring about
      complete recovery to normal of intellectual work fitness. The combined use of
      carnitine and cobamamide eliminates fluctuations in the work rate and normalizes
      the scope and productivity of intellectual work.

PMID- 1355944
TI  - 11th International Congress of Cytology. Melbourne, Australia, May 3-7, 1992.
      Abstracts.

PMID- 1355945
TI  - [The VII Congress of french speaking leprosy specialists].

PMID- 1355946
TI  - [Epidemiological study of HIV seroprevalence in a leprosy patient population in
      Senegal].
AB  - We report the findings of an epidemiological study conducted between June 1989
      and February 1990 on a population of leprosy patients in southern Senegal
      (Bignona major endemic disease sector). Two types of population were studied:
      patients living in urban areas and inmates of leprosaria. The global HIV
      seroprevalence (HIV 2 in all cases) of the leprosy-patient population was 1.15%
      (3/257): 0.8% (1/130) for the urban group and 1.5% (2/127) for the leprosaria.
      The seroprevalence rate does not differ significantly from that for the control
      group studied and for blood donors (1/221). The diagnosis of leprosy in the
      seropositive subjects had been established before 1980. None of them showed any
      sign of relapse. The immunodepression associated with the presence of HIV was
      only moderate: it was reflected in a lowering of the CD4 count and of the CD4/CD8
      ratio, but with no clinical sign of AIDS.

PMID- 1355947
TI  - Endometrial and ovarian malignancies: epidemiology, etiology and prognostic
      factors.

PMID- 1355948
TI  - [A case of testicular tumor arising in the undescended testis].
AB  - A 42-year-old man with testicular tumor arising in the left undescended testis is
      reported. The patient had bilateral cryptorchidism and was admitted to our clinic
      on March 20, 1989, complaining of a mass in the lower abdomen. Colography
      indicated complete obstruction at the sigmoid colon, and computed tomography
      showed a larger mass in the lower abdomen and paraaortic lymph node swelling, as
      well as left hydronephrosis. We suspected that a testicular tumor had arisen in
      the undescended testis, and ileus was caused by the tumor mass. Since the patient
      was in a poor condition from preexisting ileus, chemotherapy consisting of
      cisplatin, bleomycin and vinblastine (PVB regimen) was immediately started
      without confirming the histology. After two courses of PVB regimen, bilateral
      orchiectomy, retroperitoneal lymphadenectomy, and left nephrectomy were
      performed. Pathological examination of the testis and resected lymph nodes
      revealed no residual tumor cells, and we could not identify the original
      histology. Additionally, two courses of chemotherapy were performed after
      surgery. The patient is well without evidence of disease one year and ten months
      after surgery.

PMID- 1355949
TI  - Prophylactic use of apraclonidine for intraocular pressure increase after Nd:YAG
      Capsulotomies.

PMID- 1355950
TI  - Liver biochemical tests and dengue fever.
AB  - The impact of dengue on liver function was studied by biochemical tests on 125
      male and 145 female patients diagnosed with this disease during an outbreak that
      extended from November 1987 to December 1988. Abnormal levels of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, alkaline
      phosphatase, and gamma-glutamyl transpeptidase (G-GT) were observed in 93.3%,
      82.2%, 7.2%, 16.3% and 83.0% of the patients, respectively. The elevation of
      transaminases was mild to moderate in most cases, but was 10-fold greater than
      the normal upper limit for AST and ALT in 11.1% and 7.4% of the patients,
      respectively. Initially, the level of AST was greater than that of ALT,
      increasing to maximum levels nine days after the onset of symptoms, then
      decreasing to normal levels within two weeks. Results of the biochemical tests
      did not differ significantly between the cases with and without hepatitis B or
      hepatitis C virus infection, but significantly higher elevations of AST, ALT, and
      G-GT were observed in patients with episodes of bleeding. Liver biopsies of two
      patients showed features of lobular hepatitis. Of the five fatal cases, three
      died of hepatic failure. It is concluded that dengue fever may cause hepatic
      injury and transaminase elevation similar to that in patients with conventional
      viral hepatitis. In epidemic or endemic areas, dengue fever infection should be
      considered in the differential diagnosis of hepatitis.

PMID- 1355951
TI  - New H1-receptor antagonists: worth the price?

PMID- 1355952
TI  - Simulated assembly line performance following ingestion of cetirizine or
      hydroxyzine.
AB  - Twelve healthy subjects participated in three daytime work periods, in a double
      blind repeated measures Latin square design. Subjects received cetirizine (10
      mg), hydroxyzine (25 mg), or placebo at 0800. Performance was measured each day
      during eight 50-minute test periods on a simulated assembly line task between
      0830 and 1700. Before entry into the study, subjects were trained to a minimum
      80% correction rate on the performance task. Performance decrements were
      consistently associated with hydroxyzine but not with cetirizine. Subjects made
      fewer correct responses with hydroxyzine compared with both cetirizine and
      placebo. Subjectively, participants reported feeling sleepier and performing
      worse during the hydroxyzine condition than following placebo. Cetirizine,
      however, did not differ from the other two conditions on self-assessments of
      alertness or performance. These findings support the hypothesis that objective
      measures of human functioning are more specific than are subjective measures.

PMID- 1355953
TI  - Asthma as a chronic inflammatory disease and the implications for future therapy.

PMID- 1355955
TI  - Surrogate markers in AIDS.

PMID- 1355954
TI  - Pharmacologic evaluation of factor XIIIa*-like enzyme activity in equine plasma
      as a potential therapeutic avenue for the inhibition of fibrinous tissue.
AB  - Several pharmaceutical compounds were evaluated for their ability to selectively
      inhibit activated coagulation factor-XIII-like enzyme activity (eg, XIIIa*) in
      pooled equine plasma. Presence of coagulation factor-XIIIa*-like enzyme activity
      in plasma was established by assay procedures involving incorporation of the
      fluorescent amine compound, monodansylcadaverine, into purified casein, which
      served as a protein substrate. Pharmaceuticals inhibitory to coagulation factor
      XIIIa*-like enzyme activity were recognized by plasma gel formation of high
      spectrophotometric transmittance (transparency), solubility of transparent fibrin
      gels in concentrated urea solution, in conjunction with simultaneous depletion of
      native fibrinogen fractions, and production of fibrin monomer. Compounds acting
      primarily as anticoagulants were recognized by lack of plasma gel formation, but
      retaining high spectrophotometric transmittance and no detectable depletion of
      native fibrinogen fractions. Compounds failing to inhibit either thrombin
      mediated fibrinogen-fibrin transformation (ie, coagulation) or coagulation factor
      XIIIa*-like enzyme activity were recognized by opaque plasma gels caused by
      fibrin polymerization, low spectrophotometric transmittance values, and
      coinciding with depletion of native fibrinogen fractions. Pharmaceuticals capable
      of exerting selective inhibition of coagulation factor-XIIIa*-like enzyme
      activity were further classified as competitive inhibitors of phase 1 (carbamide)
      or phase 2 (terminal amine) of the transglutamination process.

PMID- 1355956
TI  - [Salazosulfapyridine in rheumatoid arthritis. A study of 49 patients].
AB  - The results of an open retrospective study of 49 patients treated with
      salazosulfapyridine (SASP) (sulphasalazine) for rheumatoid arthritis (RA) are
      reported. The patients, 7 men and 42 women, had a mean age of 53 years, and their
      mean duration of evolution of RA was 13.3 years. Sixty percent of them had
      undergone more than 3 previous disease-modifying drugs. The mean length of SASP
      treatment was 15.3 months. The initial response was favorable in 34 patients
      (69%). Treatment was ineffective and stopped in 12 cases (24.5%); the inefficacy
      was primary in 6 and tachyphylactic in the other 6. Twenty patients (41%)
      experienced at least one side effect. SASP was stopped in 11 patients (20.4%) due
      to undesirable side effects; 9 of the 11 times were during the first 2 months of
      treatment. Digestive system intolerance was the most common but led to drug
      withdrawal in less than half the patients. In all cases, mucocutaneous,
      neurosensory, hematological and hepatic side effects regressed during the month
      following SASP withdrawal. The therapeutic maintenance level was 67% at 1 year,
      60% at 18 months, 52% at 2 years and 45% at 3 years. SASP has a role in the
      treatment of relatively slightly evolved forms of RA, before prescribing
      methotrexate. The possibility of delayed intolerance reactions, notably
      hematological and hepatic, justify prolonged biological monitoring of these
      patients.

PMID- 1355957
TI  - Cystic fibrosis gene mutations and linked RFLPs in the Slovenian population.
AB  - The authors used polymerase chain reaction to analyse 56 Slovenian cystic
      fibrosis (CF) chromosomes for the presence of delta F508 and eight other most
      frequent mutations located in exons 7,11 and 20 (R347P, R334W, G551D, R553X,
      S549RA, S549RT, S549I and S1255X) of the CF gene. We also determined the
      frequency of haplotypes associated with CF for six linked RFLP markers
      (MetD/TaqI, MetH/TaqI, XV-2c/TaqI, KM-19/PstI, MP6d9/MspI and J3.11/MspI) in 27
      Slovenian CF families. delta F508 mutation was present in 55.4 percent of the CF
      chromosomes. No case of the other mutations were detected in the sample of tested
      CF chromosomes. A very high degree of association (0.88) has been found between
      DNA marker MetH and CF (as measured by the Yule's association coefficient) in our
      population. Using the RFLP markers XV-2c and KM-19, we found that 85% of delta
      F508 mutated chromosomes have a single 1 2 (B) haplotype, and that this haplotype
      is present on only 15.4 percent of CF chromosomes without this deletion.

PMID- 1355959
TI  - 99th Scientific Session of the Western Surgical Association. Colorado Springs,
      Colorado, November 15-18, 1991.

PMID- 1355958
TI  - Short- and long-term effects of insulin on tyrosine aminotransferase gene
      expression.
AB  - In the present study the relationship between changes in tyrosine
      aminotransferase (TAT) enzyme activity, cytoplasmic mRNA levels, and gene
      transcription in response to both short- and long-term exposure to insulin was
      investigated. Insulin acutely inhibited transcription of the TAT gene by 50% in
      serum-deprived rat H4 hepatoma cells. Following this initial 50% decrease in
      transcription, there was a 2.5-fold induction in TAT activity that could not be
      accounted for by a concomitant increase in TAT mRNA levels. Insulin had no effect
      on the half-life of TAT mRNA. Insulin exposure for short periods of time also
      inhibited the glucocorticoid- and cAMP-induced transcription of the TAT gene.
      Like insulin, protein synthesis inhibitors acutely inhibited basal and
      glucocorticoid-induced TAT transcription. TAT activity gradually returned toward
      basal levels after 8 h of insulin treatment. A second insulin-induced increase in
      TAT activity (3.5-fold above basal levels) was observed by 24 h of insulin
      treatment. This second phase of insulin-induced TAT activity was associated with
      elevated levels of TAT transcription and TAT mRNA levels, and therefore, unlike
      the earlier stimulation, could be accounted for by changes in gene expression.
      Thus, the insulin-mediated regulation of the TAT gene in H4 cells is complex.
      Different transcriptional and post-transcriptional mechanisms are likely to be
      involved in the biphasic responses to insulin.

PMID- 1355961
TI  - Infectivity and pathogenesis of iridescent virus type 22 in various insect hosts.
AB  - This paper reports the results of a series of laboratory experiments to determine
      the infectivity and pathogenesis of iridescent virus type 22 (IV 22) for six
      species of mosquitoes, phlebotomine sand flies and triatomid bugs. Following
      inoculation, IV 22 replicated in all of the species tested, without producing
      noticeable mortality within a 14 day observation period. Examination of the
      infected insects by immunofluorescence demonstrated large amounts of viral
      antigen in many different organs. Electron microscopy done on infected mosquitoes
      (Aedes aegypti) showed large numbers of virus particles within cells of the fat
      body, muscle tracheal and midgut epithelium. Virus replication in the mosquitoes
      was confirmed to host cell cytoplasm and was similar to that described in the
      natural blackfly (Simulium) host. Transovarial transmission of IV 22 could not be
      demonstrated in A. aegypti, and only a small percentage of mosquito larvae could
      be infected orally. Results of these experiments are compatible with observations
      of other iridescent viruses; IV 22 is highly infectious for a wide range of
      insects when introduced into their hemolymph, but it is not very infectious per
      os. These characteristics would appear to limit its value as a potential
      biocontrol agent for Diptera.

PMID- 1355960
TI  - Heterogeneity of feline herpesvirus type 1 strains.
AB  - Heterogeneity of 9 feline herpesvirus type 1 (FHV-1) strains consisting of the
      prototype C27 strain, one French isolate, six Japanese isolates, and the
      attenuated vaccine F2 strain was examined by biological, immunological, and
      molecular biological methods. No significant difference was observed in virus
      growth and antigenic properties among the strains in Crandell feline kidney cell
      cultures. Hemagglutination activity was also detected in all extracts of cells
      infected with each strain. However, in immunoblot analysis, a virus-structural
      immunogenic protein with an M(r) of 36 kDa was lacking in 2 strains, one of which
      was the vaccine F2 strain, whereas the other immunogenic proteins including three
      kinds of major glycoproteins were detected in all strains without differences in
      electrophoretic mobilities. Furthermore, when restriction endonuclease analysis
      was performed to examine the genomic heterogeneity of strains, the cleavage
      patterns with the enzyme MluI showed a genomic heterogeneity between wild and
      vaccine strains. In contrast, only a slight variation in the sizes of some
      fragments was shown with most of the 7 other enzymes used. These results
      indicated that the lack of the 36 kDa protein and the MluI cleavage pattern could
      be used as markers of the vaccine F2 strain. The specific markers are important
      not only to control the quality of the vaccine but also to evaluate the vaccine
      immunity in FHV-1 infection in cats.

PMID- 1355962
TI  - [Apud cells in endometrial cancer].
AB  - 55 endometrial carcinomas containing apud cells are studied. Correlation between
      the endocrine-metabolic disturbances and mitotic index, on the one hand, and
      number of apud cells and their product on the other, is revealed. If the
      percentage of apud cells is above 20 of all parenchymal cells, low mitotic index
      in the tumour, marked production of serotonin, calcitonin and other hormones and
      high incidence of endocrine disturbances together with a relatively favourable
      prognosis are observed. Low number of apud cells associated with high mitotic
      index and high incidence of unfavourable outcomes while the hormone production
      and endocrine disturbances were rare or absent.

PMID- 1355963
TI  - [Histogenesis of experimental renal tumors in mice].
AB  - Epithelial kidney tumours induced in CBA male mice by 1,2-dimethylhydrazine were
      studied histochemically and immunohistochemically. Histologically, 48 tumours
      studied were diagnosed as clear-cell, acidophilic or mixed adenomas located in
      the renal cortex. Gamma-glutamyl transpeptidase (GGT) was strongly positive in
      normal proximal convoluted tubules, slightly positive in the cells of Bowman
      capsule and negative in 47 of 48 tumours examined. Antibodies against the new
      antigen obtained from the mouse liver oval cells and called A6 antigen were also
      used. This antigen in normal kidney is negative in proximal tubules but always
      positive in distal tubules and collective ducts. It was also positive in all 47
      GGT-negative tumours. One tumour was GGT-positive and A6 antigen-negative. The
      conclusion is made that the majority of renal cell adenomas in mice most likely
      originate from the collective duct system and not from the proximal tubules.

PMID- 1355964
TI  - The pathogenesis of Tourette's syndrome. A possible role for hormonal and
      excitatory neurotransmitter influences in brain development.
AB  - Tourette's syndrome (TS) is associated with prominent gender differences in
      clinical expression, tics with a sexual content, and a stabilization or
      improvement of symptoms after puberty. It is herein hypothesized that some tics
      can be viewed as inappropriately expressed (normally inhibited) fragments of
      primitive motor and vocal programs involved in reproductive activity. The brain
      regions involved in TS (basal ganglia and limbic system) are proposed to be
      counterparts in humans of those functioning in primitive reproductive behavior
      whose development and organization are under sex hormone control. It is further
      hypothesized that sex hormone action is mediated by excitatory neurotransmitter
      mechanisms such that an excessive trophic effect occurs early in development and
      a neurotoxic environment emerges later on. The defective gene in TS is
      hypothesized to influence these developmental processes. This hypothesis has
      implications for the investigation of the pathogenesis of TS and for experimental
      therapeutics of the disorder.

PMID- 1355965
TI  - [Effects of dietary proteins on analgesic activity of tolerance and physical
      dependence on morphine in rats].
AB  - Effects of dietary proteins such as casein and egg albumin on analgesic activity
      of, tolerance to and physical dependence on morphine in rats were examined. There
      was no difference in analgesic activity after acute administration of morphine 10
      mg/kg, s.c. between rats treated with casein food or egg albumin food and normal
      food for 5 or 21 days. The development of tolerance to morphine analgesia in rats
      treated with albumin food but not with casein food was suppressed during daily
      morphine 10 mg/kg, s.c. on 5 consecutive days. Rats were treated with casein or
      albumin food mixed with morphine (0.5 mg/g of food) for 5 days. Morphine intake
      in rats treated with albumin food was significantly decreased as compared to that
      with morphine admixed casein or normal food. Body weight loss by naloxone in
      morphine-dependent rats was significantly less in both casein food and albumin
      food groups than in the normal food group. These results suggest that chronic
      dietary treatment with albumin may produce a partial inhibition of development of
      tolerance to morphine analgesia and that with casein may attenuate morphine
      withdrawal manifestation in rats.

PMID- 1355966
TI  - Metastasis formation in human solid tumors: phenotypic characteristics of early
      metastatic cells.

PMID- 1355967
TI  - Alcohol-preferring rats have fewer dopamine D2 receptors in the limbic system.
AB  - Dopamine D2 receptors in nucleus accumbens, olfactory tubercle and caudate
      nucleus of Sardinian ethanol-preferring (SP), and non-preferring (SNP) rats were
      compared by using [3H]YM-09151-2 binding. SP rats exhibited, in each area, lower
      density of D2 receptors than SNP and unselected Wistar (UW) rats. The results
      suggest that reduction in D2 receptors in SP rats may be relevant to their innate
      preference for alcohol.

PMID- 1355968
TI  - The effects of MDMA and other methylenedioxy-substituted phenylalkylamines on the
      structure of rat locomotor activity.
AB  - The effects of acute subcutaneous injections of methylenedioxy-substituted
      phenylalkylamines in rats were tested in an unconditioned motor behavior paradigm
      using the Behavioral Pattern Monitor (BPM). Based on a previously developed
      scaling hypothesis and the associated temporal and spatial scaling exponents
      (alpha and d), the effects of racemic and S(+) 3,4-methylenedioxyamphetamine
      (MDA), racemic, S(+) and R(-) 3,4-methylenedioxymethamphetamine (MDMA), racemic N
      methyl-1-(1,3-benzodioxol-5yl)-2-butanamine (MBDB), racemic N-ethyl-3,4
      methylenedioxyamphetamine (MDEA), 2,5-dimethoxy-4-iodoamphetamine, and
      methamphetamine were characterized using the d-alpha plane. Three distinct dose
      response patterns were observed. 1) S(+) and (+/-)MDA had pronounced dose
      dependent effects on the structure of motor behavior, which were characterized by
      long-straight path movements and minimal changes in the amount of motor behavior.
      2) (+/-)MDMA and (+/-)MBDB dose-dependently changed patterns of movements towards
      long-straight paths together with dose-dependent increases in the amount of motor
      activity. 3) S(+)MDMA and (+/-)MDEA produced dose-related increases in the amount
      of motor activity with minimal changes of the movement patterns in the BPM.
      Comparisons with the existing drug discrimination, operant, and biochemical
      literature on these compounds lead to the conclusion that the observed effects in
      the d-alpha plane do not simply reflect the different effects of these compounds
      as dopamine or serotonin (5-HT) releasers or reuptake inhibitors and do not
      parallel their different abilities to exhibit hallucinogen-like effects. Instead,
      indirect 5-HT1 effects appear to contribute substantially to the differential
      changes in the amount and structure of motor behavior induced by the
      phenylalkylamines. This conclusion may provide an encouraging rationale to
      develop postsynaptically effective "entactogens," a potential new drug category
      as adjunctive psychotherapeutics.

PMID- 1355969
TI  - Neurotransmitters are important, but so is metabolism. Commentary on "The current
      status of PET scanning with respect to schizophrenia".

PMID- 1355970
TI  - Commentary on "The current status of PET scanning with respect to schizophrenia".

PMID- 1355971
TI  - Renal tubular enzyme effects of clarithromycin in comparison with gentamicin and
      placebo in volunteers.
AB  - This study assessed the potential nephrotoxicity of clarithromycin in comparison
      with gentamicin and placebo. Increased urinary excretion of alanine
      aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) served as markers
      of renal tubular injury. The study utilised a multiple-dose, double-blind,
      randomised, parallel group design. 14 healthy male subjects received 1 of 3
      treatment regimens: (a) clarithromycin 500 mg orally every 12h for 13 doses and
      intravenous placebo every 8h (n = 5); (b) oral placebo every 12h and intravenous
      placebo every 8h (n = 4); and (c) intravenous gentamicin 1.7 mg/kg every 8h for
      19 doses and oral placebo every 12h (n = 5). 24h urine collections were obtained
      daily for determinations of AAP and NAG activities. Gentamicin produced
      statistically significant increases (p less than 0.0001) in AAP and NAG
      excretion, with increases as early as the first and second day of dosing.
      Clarithromycin, when compared with placebo, did not produce significant
      elevations in AAP or NAG activity. On the basis of these data, it is unlikely
      that usual doses of clarithromycin have significant potential for causing
      nephrotoxicity.

PMID- 1355972
TI  - Microiontophoresis and single-unit recordings of serotonergic neurons in the
      awake cat.

PMID- 1355973
TI  - Histopathologic changes of the spleen in suckling rats inoculated with Hantaan
      virus.
AB  - The purpose of this study is to delineate the histopathologic findings of the
      spleen after Hantaan viral inoculation, which is the largest lymphoid organ in
      rats, and to identify the viral location by anti-Hantaan virus (HTNV) monoclonal
      antibody. All the sixty one suckling rats of less than twenty four hours of age
      were used. Except twenty one rats of control group, twenty-five rats inoculated
      intracerebrally for the early change and fifteen suckling rats inoculated
      intramuscularly for the late change were uniformly susceptible to lethal
      infection with the ROK 84-105-1 strain of seed HTNV. The characteristic
      histopathologic findings were; appearance of macrophages below the splenic
      capsule on the 3rd day, small lymphocytes around the periarteriolar sheath on the
      5th day increasing in numbers on the 7th day, and a markedly expanded marginal
      zone with some immunoblasts and plasma cells as well as decreased extramedullary
      hematopoiesis on the 9th and 14th days. Time of onset of histopathologic changes
      in spleen thickness, appearance of medium and large lymphocytes and degree of
      extramedullary hematopoiesis were influenced by inoculation route, whereas
      expansion of the marginal zone was affected by postnatal age.

PMID- 1355974
TI  - The effect of luminal flow in rabbit carotid artery on transmural fluid
      transport.
AB  - The steady-state flow of fluid across the wall of the isolated rabbit common
      carotid artery has been measured in the presence and absence of flow within the
      lumen of the vessel. The perfusate solution contained either 10 or 40 mg ml-1
      albumin and transmural flux was measured by monitoring the rate of movement of
      fluid into a chamber enclosing the artery. Vasomotion was minimized by the
      inclusion of the vasodilator sodium nitrite in both the perfusate and the outer
      bathing solution. A relatively slow luminal flow caused a reversible increase in
      the transmural flux by 20-30% relative to the value in the absence of flow. The
      mechanism responsible for the increase is not clear, but since it was not
      affected by the H1 antagonist, mepyramine, it would not appear to have been
      mediated by histamine release.

PMID- 1355975
TI  - Effects of the beta-adrenergic agonist, ritodrine, and insulin on plasma
      potassium concentrations in fetal lambs.
AB  - Prolonged infusion of the beta 2-adrenergic agonist, ritodrine, into sheep during
      late pregnancy decreased maternal plasma K+ from 3.6 to 2.5 mmol l-1 during the
      first 6-8 h of infusion, as it does during tocolysis in women. This decrease was
      not accompanied by significant change in fetal plasma K+ concentration. Ritodrine
      infusion (1-3.5 micrograms kg-1 min-1) directly into the fetus also did not
      decrease fetal plasma K+ significantly. In contrast, insulin (2.5 mU kg-1 min-1),
      infused together with glucose (3.6 mg kg-1 min-1) directly into the fetus
      decreased fetal plasma K+ concentration by 0.8 mmol l-1 within 1 h. The results
      suggest immaturity in beta 2-adrenergic receptor regulation of electrogenic K+
      uptake by muscle in fetal lambs.

PMID- 1355976
TI  - Enhanced electrogenic secretion in vitro by small intestine from glucagon-treated
      rats: implications for the diarrhoea of starvation.
AB  - Glucagon treatment of fed rats (50 micrograms I.P. every 6 h for 3 days) induces
      significant increases in vitro of the basal short-circuit currents of the jejunum
      (52%) and proximal ileum (81%) and in their electrogenic secretory responses to
      stimulation by bethanechol, a muscarinic agonist. The results support a role for
      glucagon in the intestinal hypersecretion observed in starvation and nutrient
      deprivation.

PMID- 1355977
TI  - Roles of PKA and PKC in facilitation of evoked and spontaneous transmitter
      release at depressed and nondepressed synapses in Aplysia sensory neurons.
AB  - Two second messenger pathways, one that uses the cAMP-dependent protein kinase A
      (PKA), the other that uses protein kinase C (PKC), have been found to contribute
      to the short-term presynaptic facilitation of the connections between the sensory
      neurons in Aplysia and their target cells, the interneurons and motor neurons of
      the gill-withdrawal reflex. To study their relative contributions as a function
      of the previous history of the neuron's activity, we have examined the effects of
      inhibiting PKA (using Rp-cAMPS) and PKC (using H7) on the short-term facilitation
      of spontaneous release as well as of the evoked release induced by serotonin at
      nondepressed, partially depressed, and highly depressed synapses. Our results
      suggest that whereas activation of PKA is sufficient to trigger the facilitation
      of nondepressed synapses, activation of both PKA and PKC is required to
      facilitate depressed synapses, with the contribution of PKC becoming
      progressively more important as synaptic transmission becomes more depressed.

PMID- 1355978
TI  - [Restriction fragment length polymorphisms of chloroplast DNA and the intergenic
      spacer of rRNA gene in cultivated barley of China].
AB  - A sample of 80 accessions collected from several major barley growing areas in
      China was assayed for restriction fragment length polymorphisms at two regions of
      the chloroplast DNA and the intergenic spacer of the ribosomal RNA gene (rDNA).
      The results showed that the spacer length was highly polymorphic and 8 spacer
      length variants constituting 8 phenotypes were observed in this sample. It is
      also clear that the spacer length variants and the phenotypes were differentially
      distributed in different geographical regions, probably due to adaptation of the
      genotypes to the local environments. We did not detect variation in the two
      chloroplast fragments, indicating that the variability of chloroplast DNA is low
      in cultivated barley.

PMID- 1355979
TI  - Signalling in human tumour infiltrating lymphocytes: the CD28 molecule is
      functional and is physically associated with the CD45R0 molecule.
AB  - The CD28 T cell activation pathway was functional in human tumour infiltrating
      lymphocytes (TIL) and can induce strong proliferation, lymphokine release and
      calcium mobilisation. Conversely, TIL responded poorly to stimulation via CD2,
      and CD28 did not synergise with CD2, which is at variance with that observed
      using peripheral lymphocytes from the same patients. On stimulation with anti
      CD28 the monoclonal antibody, most TILs, which were CD3+, CD28+ and CD45R0+ at
      the beginning of culture, co-expressed both high (CD45RA) and low (CD45R0)
      molecular weight isoforms of CD45. CD28 was associated with the CD45R0 isoform at
      the cell surface of activated TIL, as demonstrated by immunoprecipitation and
      immunoenzymatic assay. Thus CD28 can substitute for CD3 in TIL leading to the
      expansion of functional lymphocytes and to the amplification of antitumour immune
      response.

PMID- 1355980
TI  - Direct effects of tamoxifen on growth hormone secretion by pituitary cells in
      vitro.
AB  - There is now strong evidence to suggest that insulin-like growth factor I (IGF-I)
      plays an important role in breast cancer proliferation. Recently we observed that
      tamoxifen-treated stage I breast cancer patients have serum IGF-I levels
      significantly lower than placebo-treated patients. Since IGF-I is growth hormone
      (GH) dependent, we have tested the hypothesis that tamoxifen alters serum IGF-I
      levels through direct inhibition of GH secretion. Immature lamb pituitary
      cultures were examined for acute (3 h) or chronic (1-6 day) effects of the drug,
      using doses (0.1-10 mumol/l) based on known steady state levels in patients on
      tamoxifen therapy (0.31-3.1 mumol/l). Tamoxifen had a direct, dose-related,
      inhibitory effect on GH release from pituitary somatotropes, during acute as well
      as chronic treatment. The 10 mumol/l dose consistently decreased both basal and
      growth hormone releasing factor stimulated GH release. These in vitro data are
      consistent with our hypothesis that tamoxifen suppresses serum IGF-I levels by
      acting at the pituitary to inhibit GH release.

PMID- 1355982
TI  - Adjuvant therapy of breast cancer.

PMID- 1355983
TI  - Adjuvant chemotherapy of axillary lymph-node-positive breast cancer.

PMID- 1355981
TI  - Effects of alpha-adrenoceptor and of combined sympathetic and parasympathetic
      blockade on cardiac performance and vascular resistance.
AB  - 1. Cardiac performance and vascular resistance was studied in seven healthy men
      by radionuclide cardiography and venous plethysmography before and after alpha
      adrenoceptor blockade with phentolamine and after combined alpha-adrenoceptor,
      beta-adrenoceptor (propranolol) and parasympathetic (atropine) blockade. 2.
      During alpha-adrenoceptor blockade heart rate and cardiac output increased
      considerably and left ventricular ejection fraction increased because of
      increased contractility. Systemic vascular resistance fell both during alpha
      adrenoceptor blockade alone and during combined blockade. The increase in calf
      blood flow was of the same magnitude after combined blockade and after alpha
      adrenoceptor blockade alone, and was considerably higher than the fall in
      systemic vascular resistance. Plasma catecholamine concentrations increased after
      phentolamine, but the changes were blunted when propranolol and atropine were
      added. 3. These results indicate that peripheral vasoconstriction especially that
      exerted by alpha-adrenoceptor nervous tone in skeletal muscle restricts left
      ventricular emptying of the intact heart. During pharmacologic blockade of the
      sympathetic and parasympathetic nervous system at rest the chronotropic state is
      augmented, whereas preload and inotropy are unaffected.

PMID- 1355984
TI  - The node-negative problem: to treat or not to treat.

PMID- 1355985
TI  - Defining the high-risk breast cancer patient.

PMID- 1355986
TI  - Models for weighing benefits and toxicities.

PMID- 1355987
TI  - Financial considerations in the use of adjuvant chemotherapy.

PMID- 1355988
TI  - The use of adjuvant therapy in patients treated with conservative surgery and
      radiotherapy.

PMID- 1355989
TI  - Treating the relapsed patient.

PMID- 1355990
TI  - Unanswered questions in the adjuvant therapy of breast cancer.

PMID- 1355991
TI  - Statistical methods for early breast cancer trials.

PMID- 1355992
TI  - Neoadjuvant chemotherapy.

PMID- 1355993
TI  - Altering cell kinetics with endocrine therapy.

PMID- 1355994
TI  - Evolving concepts in the adjuvant systemic therapy of operable breast cancer.

PMID- 1355995
TI  - Polypeptide growth factors: their potential value in the management of breast
      cancer patients.

PMID- 1355996
TI  - Immunotherapy of breast cancer.

PMID- 1355998
TI  - Adjuvant chemotherapy of breast cancer. NIH consensus development conference,
      July 14-16, 1980.

PMID- 1355997
TI  - Breast cancer chemoprevention.

PMID- 1355999
TI  - Adjuvant chemotherapy for breast cancer. NIH consensus development conference,
      September 9-11, 1985.

PMID- 1356000
TI  - Early stage breast cancer: consensus statement. NIH consensus development
      conference, June 18-21, 1990.

PMID- 1356001
TI  - The nature of the benefit.

PMID- 1356002
TI  - Adjuvant endocrine therapy of breast cancer.

PMID- 1356003
TI  - Successful peripheral blood stem cell autotransplantation in a child with
      advanced B-cell lymphoma.
AB  - A 2-year-old boy with B-cell lymphoma (stage IV) in the first complete remission
      received myeloablative treatment followed by peripheral blood stem cell
      autotransplantation and is surviving event-free for 18 months. Reconstitution of
      all cell lines occurred very rapidly, ie, a level of 1000 leukocytes per
      microliter was reached after 9 days, that of 500 granulocytes per microliter
      after 10 days, and platelets were substituted only once. This result suggests
      that PBSCT can be safely employed during consolidation therapy for malignant
      disorders because of its short duration of bone marrow suppression.

PMID- 1356004
TI  - Fractionated total body irradiation, high-dose melphalan, etoposide, and
      carboplatin (FTBI-MEC) for autologous stem cell transplantation in children with
      advanced neuroblastoma and primitive neuroectodermal tumor.

PMID- 1356005
TI  - Complete remission of 4 years following autologous blood stem cell
      transplantation in a child with early relapse of translocation t(9;X) acute
      lymphoblastic leukemia.

PMID- 1356006
TI  - The zebrafish homeobox gene hox[zf-114]: primary structure, expression pattern
      and evolutionary aspects.
AB  - It is gradually becoming accepted that vertebrate homeobox genes, like their
      counterparts in Drosophila, are crucial for normal development of the embryo.
      Most vertebrate homeoboxes reported so far are related to the Drosophila
      Antennapedia (Antp) sequence, and here we describe hox[zf-114], a novel Antp-like
      homeobox gene from the zebrafish. The sequence of the hox[zf-114] homeodomain
      indicates that this gene could be a member of a subfamily defined by the mouse
      Hox-1.5/-2.7/-4.1 genes. However, the evolutionary origin of hox[zf-114] is
      unclear and, based on the putative protein sequence, we conclude that it is not
      directly homologous to Hox-1.5, Hox-2.7 or Hox-4.1, or to other known mammalian
      homeobox genes. Nevertheless, as revealed by in situ hybridization, hox[zf-114]
      exhibits a spatial expression pattern typical for vertebrate Antp-like homeobox
      genes. Transcripts are detected in the posterior hindbrain, where a sharp
      anterior border of expression is observed, and throughout the spinal cord. The
      hox[zf-114] gene is also active in a region that gives rise to the pectoral fins.
      These findings suggest a role for hox[zf-114] in anteroposterior patterning of
      the neural tube and in pectoral fin development.

PMID- 1356007
TI  - Pyroglutamyl [correction of Pyroglutamil] -peptidase I activity in the cortex of
      the cat brain during development.
AB  - Thyrotropin Releasing Hormone (TRH) is a principal regulator of thyroid system
      function. However, significant concentrations of TRH were found throughout the
      central nervous system, the cortex being one of the areas most richly endowed
      with thyroliberin. Research concerning the functional role of this brain peptide
      is performed, in part, by studying peptidase enzymes which may be involved in the
      inactivation of the peptide. The pGlu-His bond is cleaved by two pyroGlu
      peptidases: I (soluble) and II (membrane-bound). In the present investigation,
      developmental activity of the soluble form is described in the cortices of the
      cat brain. The selected maturation stages were 15 and 30 days postnatal. The
      cortices were the frontal, parietal, area 17 and areas 18 and 19 as a whole,
      distinguishing brain hemispheres in all cases. PyroGlu-aminopeptidase I activity
      increased significantly with age in all the brain regions except area 17. It is
      suggested that this enzyme activity plays a part in the neurochemical changes
      that take place during brain maturation.

PMID- 1356008
TI  - Conserved classes of homeodomains in Schistosoma mansoni, an early bilateral
      metazoan.
AB  - Genes containing a homeobox can be divided into classes based on the distinctive
      peptide sequences of their diverged homeodomains. Many of these classes,
      including Antennapedia, engrailed and paired, are strongly conserved in higher
      multicellular animals, but have not previously been found in platyhelminths, the
      flatworms which represent the most primitive bilateral metazoans. We have
      screened cDNA libraries of the platyhelminth Schistosoma mansoni using a
      degenerate oligonucleotide derived from the third helix of the homeodomain, and
      have identified numerous schistosome homeobox-containing sequences, including
      members of the Antennapedia, engrailed and paired classes. The schistosome
      homeodomain sequences are more similar to the higher animals sequences in their
      respective classes than they are to each other, indicating that the establishment
      of these three distinctive classes is at least as ancient as the flatworms. Our
      data suggest that the ancestral functions of the Antennapedia, engrailed and
      paired classes involve fundamental features of all bilateral metazoan
      development. The putative full-length coding sequence of the S. mansoni en
      homologue is presented.

PMID- 1356009
TI  - Isolation and analysis of embryonic expression of Hox-4.9, a member of the murine
      labial-like gene family.
AB  - Two members of the murine labial (lab) subfamily of Antennapedia-like homeobox
      containing genes, Hox-1.6 and Hox-2.9, have been identified previously. Here we
      describe a third member genetically linked to the Hox-4 cluster on chromosome 2.
      This gene, designated Hox-4.9, is similar in structure to the other lab subfamily
      members. However, little coding sequence other than the homeobox and sequences
      immediately upstream of it have been conserved. By in situ hybridization
      analysis, Hox-4.9 mRNA is first detected at the end of the late streak stage
      (E7.75) in presumptive lateral and extraembryonic mesoderm. During early
      neurogenesis (E8.0-8.5), Hox-4.9 is detected solely in lateral mesoderm; its lack
      of expression in somitic mesoderm and the neural tube makes it unique among the
      Hox genes. By late neurogenesis and through mid-gestation (E9.0-E11.5), Hox-4.9
      is no longer detected in lateral mesoderm but is found instead in a restricted
      region of presumed trunk neural crest and in the dermatome. These data are
      discussed in comparison with what is known about expression of the other members
      of the lab subfamily.

PMID- 1356010
TI  - Proceedings of the 4th International Congress on Hormones and Cancer. Amsterdam,
      The Netherlands, September 1991.

PMID- 1356011
TI  - Novel antitumor peptide hormones and their effect on signal transduction.
AB  - A series of novel gonadotropin releasing hormone (GnRH) and Somatostatin analogs
      have been developed in our laboratory and were screened for antiproliferative and
      signal transduction inhibitory effect. Our GnRH analog Folligen, had significant
      antitumor activity on DMBA induced mammary carcinomas in rats without blocking
      ovarian functions. The direct effect of Folligen and Buserelin has been compared
      on the human breast cancer cell line MDA-MB-231. Folligen was found to be more
      effective in inhibiting cell proliferation and significant differences were found
      in the signal transduction pathways activated by these analogs. Our novel
      Somatostatin analogs were screened for tyrosine kinase inhibition and for
      antiproliferative effect on human colon tumor cells and for growth hormone (GH)
      release inhibition in vitro and in vivo. The analog TT-2-50 was significantly
      more active inhibiting GH release in superfused rat pituitary cells and in vivo
      than native Somatostatin and it strongly inhibited tyrosine kinase and
      proliferation while it stimulated protein kinase C activity.

PMID- 1356012
TI  - Prognostic factors in human primary breast cancer: comparison of c-myc and
      HER2/neu amplification.
AB  - Amplification of oncogenes in primary tumours may have prognostic and/or
      therapeutic significance for patients with breast cancer. We have studied
      HER2/neu and c-myc amplification together with steroid receptors in human primary
      breast tumours and related the outcome with (relapse-free) survival. A strong
      inverse correlation was found between HER2/neu amplification and the presence of
      oestrogen and progesterone receptors. Actuarial 5-years survival showed that
      breast cancer patients with c-myc amplification in their primary tumours
      experience a shorter relapse-free survival, especially in node-negative and in
      receptor-positive tumours, whereas HER2/neu amplification may be of prognostic
      value for overall survival in receptor-negative tumours. Overall, in our hands, c
      myc amplification appeared to be a more potent prognosticator than HER2/neu
      amplification in human primary breast cancer.

PMID- 1356013
TI  - Somatostatin receptor imaging in the diagnosis and treatment of neuroendocrine
      tumors.
AB  - Somatostatin analogs are used in the control of hormonal hypersecretion and tumor
      growth of patients with acromegaly, islet cell carcinomas and carcinoids.
      Recently we showed that somatostatin receptor positive tumors can be visualized
      in vivo after the administration of radioactive isotope-labelled somatostatin
      analogs. Receptor imaging was positive in 18/21 islet cell tumors, 30/31
      carcinoids, 26/28 paragangliomas, 9/14 medullary thyroid carcinomas, 5/7 small
      cell lung cancers, 6/7 neuroblastomas, 38/49 primary breast cancers, and 0/18
      pancreatic adenocarcinomas. Also 11/11 meningiomas, 4/4 astrocytomas and 0/3
      glioblastomas could be visualized. Somatostatin receptor imaging is an easy,
      harmless and painless diagnostic method. It is an in vivo method for the
      recognition of neuroendocrine cancers. It localizes multiple and/or metastatic
      tumors, predicts the successful control of hormonal hypersecretion by octreotide
      and seems of prognostic value in certain types of cancer. This scintigraphic
      method might help in patient selection for clinical trials with somatostatin
      analogs in the treatment of neuroendocrine cancers.

PMID- 1356014
TI  - Hormonal regulation of c-erbB-2 oncogene expression in breast cancer cells.
AB  - Expression of the c-erbB-2 (neu, HER-2) oncogene is found to be subjected to
      hormonal and developmental regulation in normal as well as neoplastic mammary
      cells. We have previously reported that estrogens inhibit c-erbB-2 expression at
      both the mRNA and protein level in estrogen receptor (ER)-positive, but not in ER
      negative, breast cancer cell lines. Reversion of c-erbB-2 inhibition is seen with
      tamoxifen. The effect on c-erbB-2 expression of several other hormones and
      factors, which influence mammary cell growth and differentiation, has been
      studied. Our observations indicate that, in normal and neoplastic mammary cells,
      c-erbB-2 expression is inversely related to cell proliferation. While estrogens,
      anti-estrogens and cAMP clearly regulate c-erbB-2 mRNA levels, epidermal growth
      factor dramatically decreases the c-erbB-2 protein without affecting the level of
      c-erbB-2 mRNA. Therefore, different signals converging in terms of cell
      proliferation regulate c-erbB-2 expression by different molecular mechanisms.

PMID- 1356015
TI  - The role of erbB-2 and its ligands in growth control of malignant breast
      epithelium.
AB  - The erbB-2 (HER-2, neu) protooncogene is overexpressed on the surface of about
      25% of human breast cancers. It is homologous to epidermal growth factor receptor
      and a putative growth factor receptor. Overexpression in breast, ovarian and
      gastric cancers is associated with a worse prognosis. We have recently discovered
      two ligands for this receptor. They both induce receptor phosphorylation. At low
      concentrations both induce clonogenic growth of overexpressing cells; at higher
      concentrations both are growth inhibitory. Both can overcome the inhibitory
      effects of both monoclonal antibodies directed against the ligand binding site
      and soluble extracellular domain. These ligands may form an attractive basis for
      antitumor therapy.

PMID- 1356016
TI  - Somatostatin receptors in human cancer: incidence, characteristics, functional
      correlates and clinical implications.
AB  - Somatostatin receptors (SS-R) have been identified in membrane homogenates or
      tissue sections from several hundred tumors. SS-R were found in most
      neuroendocrine tumors, i.e. GH and TSH producing pituitary tumors, endocrine
      gastroenteropancreatic (GEP) tumors, paragangliomas, pheochromocytomas, medullary
      thyroid carcinomas (MTC) and small cell lung carcinomas. SS-R were also expressed
      in a majority of malignant lymphomas, in several brain tumors (all meningiomas,
      most astrocytomas) and in breast tumors. The majority of tumors expressing SS-R
      are rather differentiated (i.e. astrocytomas vs glioblastomas), but exceptions
      exist (high grade malignant lymphomas). An inverse relationship exists between SS
      R and receptors for epidermal growth factor (EGF-R) incidence in lung tumors,
      glial tumors and most breast tumors, whereas meningiomas express simultaneously
      both receptors. A minority of tumors (ovarian tumors, MTC, insulinomas) express a
      subtype of SS-R, characterized by low affinity for the octapeptide SS analog
      octreotide. The function mediated by SS-R in human tumors may differ according to
      the tumor type. SS-R in pituitary and GEP tumor mediate hormone secretion
      inhibition with, in addition, possibly some antiproliferative effects. In
      meningiomas, however, activation of SS-R inhibits forskolin-stimulated adenylate
      cyclase activity, and weakly stimulates proliferation. Whereas SS-R seem to
      mediate antiproliferative effects in animal models and cell lines of lymphomas,
      breast and lung tumors, such an effect has not yet been convincingly documented
      in human primary tumors. The clinical implications of the presence of SS-R in
      tumors are manyfold: (1) as a predictive marker for efficient therapy with
      octreotide in pituitary and GEP tumors; (2) as a diagnostic marker: for
      pathobiochemical classification of tumors, using in vitro detection methods; for
      clinical evaluation using in vivo scanning techniques; (3) as a prognostic
      marker; and (4) as a potential radiotherapeutic target.

PMID- 1356017
TI  - Modulation of the agonist activity of antisteroids by a novel cis-acting element.
AB  - The amount of agonist activity displayed by the antiglucocorticoid dexamethasone
      mesylate (Dex-Mes) for the induction of tyrosine aminotransferase (TAT) in rat
      hepatoma cells is greater than for glutamine synthetase and varies over a period
      of weeks. This variation, which has been reproduced over a period of 40 h by
      changing the density of the cells, suggests the involvement of a trans-acting
      factor. The target of this proposed trans-acting factor has now been localized to
      the region between -3.9 to -2.9 of the rat TAT gene from experiments with cells
      that were stably transfected with hybrid TAT/CAT constructs. Deletion experiments
      with transiently transfected TAT/tk promoter/CAT constructs revealed that this
      entire activity could be conveyed by a 21 bp sequence of the TAT gene. Gel shift
      experiments support the binding of a factor(s) to this 21 bp sequence. Thus the
      activity of the antagonist Dex-Mes is relatively independent of steroid structure
      and is largely determined by the further interactions of a trans-acting factor
      with the cis-acting sequence. We call this novel sequence a glucocorticoid
      modulatory element. A model is advanced which accounts for almost all of the
      results concerning TAT induction by glucocorticoids. This same model may also be
      useful in explaining why the amount of agonist activity of most antisteroids
      varies, even for different genes within the same cell.

PMID- 1356018
TI  - Signal transduction by the neu/erbB-2 receptor: a potential target for anti-tumor
      therapy.
AB  - The neu/erbB-2 protooncogene encodes a transmembrane tyrosine kinase homologous
      to receptors for polypeptide growth factors. The oncogenic potential of the
      presumed receptor is released through multiple genetic mechanisms including a
      point mutation, truncation of non-catalytic sequences and overexpression. The
      latter mechanism appears to be relevant to human cancers as elevated expression
      of the neu/erbB-2 gene is frequently observed in solid tumors of various
      adenocarcinomas. It is therefore conceivable that strategies aimed at the
      biochemical mechanism of action of the neu/erbB-2 tyrosine kinase may contribute
      to the treatment of certain human cancers. To this aim we undertook a multiple
      research approach consisting of the following directions: (i) The neu/erbB-2
      ligand--a systematic screening of potential biological sources of the
      hypothetical hormone molecule, that presumably binds to the neu/erbB-2 protein,
      resulted in detection of a candidate activity in the medium of certain cultured
      transformed cells. Partial purification indicated that the factor is a 30-35 kDa
      glycoprotein. Further studies revealed several biochemical characteristics of the
      factor that may be helpful for complete purification and structural analysis of
      this novel hormone. (ii) Signal transduction by neu/erbB-2--using a chimeric
      receptor approach and various mutants we found that all the oncogenic forms of
      the neu/erbB-2 are constitutively coupled, both physically and functionally, to a
      multi-protein complex of signaling molecules. The latter includes the
      phosphatidylinositol-specific phospholipase C gamma and a phosphatidylinositol
      kinase. Thus, the metabolism of inositol lipids is probably a major biochemical
      pathway utilized by the neu/erbB-2 tyrosine kinase. (iii) Tumor inhibitory
      antibodies--we generated a panel of monoclonal antibodies to the presumed
      receptor. Surprisingly, some antibodies almost completely inhibited the growth of
      tumor cells in athymic mice, whereas one antibody significantly accelerated the
      rate of tumor growth in animals. Interestingly, the inhibitory antibodies
      conferred a mature phenotype to cultured breast cancer cells, implicating
      terminal differentiation in tumor retardation.

PMID- 1356019
TI  - Role of the extracellular matrix in age-related modifications of the rat aorta.
      Ultrastructural, morphometric, and enzymatic evaluations.
AB  - Connective tissues such as blood vessels are known to be greatly affected by age
      because of impaired functional properties and increased susceptibility to
      diseases. With the aim of providing further information on the role of the
      extracellular matrix in age-related modifications, we investigated the aorta in
      the rat model from birth to senescence by means of morphological and morphometric
      observations and by evaluation of lysyl oxidase activity. Results focused on the
      dramatic vascular rearrangements due to progressive fibrosis of the extracellular
      matrix and on prominent elastin modifications. The presence of lysyl oxidase
      activity, even in the oldest animals, might be at least partly responsible for
      the increased stiffness of the aging extracellular matrix. The striking age
      related remodeling of the aortic architecture and the alterations of the
      interactions between cellular and extracellular compartments might greatly
      influence the functional properties of the arterial wall in senescence, at least
      contributing to the consequences of some apparently age-related vascular
      disorders.

PMID- 1356020
TI  - [Beta-blockers in glaucoma].
AB  - The paper presents the main beta-blockers used in glaucoma therapy, the common
      international nomination and the commercial nominations of these therapeutical
      agents which have opened up new prospects in the medication of glaucoma. Some
      pharmacological properties of the beta-blockers are reviewed: the beta
      adrenolytic strength, the pharmacodynamic properties, the pharmacokinetic
      effects, the action principle, the therapeutical effects and also the local and
      general side effects of the beta-blockers used in glaucoma therapy.

PMID- 1356021
TI  - pH and kinetic isotope effects on the reductive half-reaction of D-amino acid
      oxidase.
AB  - Primary deuterium kinetic isotope and pH effects on the reduction of D-amino acid
      oxidase by amino acid substrates were determined using steady-state and rapid
      reaction methods. With D-serine as substrate, reduction of the enzyme-bound FAD
      requires that a group with a pKa value of 8.7 be unprotonated and that a group
      with a pKa value of 10.7 be protonated. The DV/Kser value of 4.5 is pH
      independent, establishing that these pKa values are intrinsic. The limiting rate
      of reduction of the enzyme shows a kinetic isotope effect of 4.75, consistent
      with this as the intrinsic value. At high enzyme concentration (approximately 15
      microM) at pH 9,D-serine is slightly sticky (k3/k2 = 0.8), consistent with a
      decrease in the rate of substrate dissociation. With D-alanine as substrate, the
      pKa values are perturbed to 8.1 and 11.5. The DV/Kala value increases from 1.3 at
      pH 9.5 to 5.1 at pH 4, establishing that D-alanine is sticky with a forward
      commitment of approximately 10. The effect of pH on the DV/Kala value is
      consistent with a model in which exchange with solvent of the proton from the
      group with pKa 8.7 is hindered and is catalyzed by H2O and OH- above pH 7 and by
      H3O+ and H2O below pH 7. With glycine, the pH optimum is shifted to a more basic
      value, 10.3. The DV/Kgly value increases from 1.26 at pH 6.5 to 3.1 at pH 10.7,
      consistent with fully reversible CH bond cleavage followed by a pH-dependent
      step. At pH 10.5, the kinetic isotope effect on the limiting rate of reduction is
      3.4.

PMID- 1356022
TI  - Cells induced to express a human immunodeficiency virus type 1 envelope gene
      mutant inhibit the spread of wild-type virus.
AB  - The feasibility of using a trans-dominant interfering human immunodeficiency
      virus type 1 (HIV-1) envelope mutant for inducible gene therapy of HIV infection
      was investigated. Genes encoding wild-type or mutant glycoproteins were
      introduced into CD4+ cells, where they were stably maintained but not expressed
      until induced. Envelope (env) gene expression was dependent upon the viral
      regulatory protein Tat. Induction of the mutant env resulted in resistance to
      cytopathic effects mediated by wild-type envelope and decreased infectious vector
      virus production. When cells containing the mutant env gene were infected with
      wild-type virus, viral spread was inhibited. The fact that maintenance of the env
      gene was stable over time suggests that inducible gene therapy using the
      dominantly interfering env mutant may be a feasible approach to slowing the
      progression of HIV-1 disease.

PMID- 1356023
TI  - Variations of plasma creatine kinase in rabbits following repetitive blood
      sampling effects of pretreatment with acepromazine, carazolol and dantrolene.
AB  - Plasma creatine kinase activity increased significantly (P less than 0.001) in
      rabbits sampled every two hours for 12 hours (mean from 509 to 2242 U/l), but did
      not change when rabbits had been accustomed to laboratory handling procedures for
      two weeks. This increase was not alleviated or only moderately by pretreatment
      with acepromazine (per os, 2.5 mg.kg-1), carazolol (intravenously, 0.05 mg.kg-1)
      or dantrolene (intravenously, 1.0 mg.kg-1). Thus, when using plasma creatine
      kinase in rabbits, e.g. to test muscle damage or local tolerance of drugs,
      animals should be made familiar with laboratory procedures before any experiment.

PMID- 1356024
TI  - Sleep deprivation and impaired cognition. Possible role of brain catecholamines.
AB  - To assess the role of brain catecholamines in cognitive decline associated with
      sleep deprivation, 40 healthy male volunteers were randomized to conditions of
      total sleep deprivation or 40.5 h of rest. Within each sleep condition, subjects
      were further randomized to treatment with a 2-day regimen of placebo or alpha
      methyl-para-tyrosine (AMPT), a catecholamine synthesis inhibitor. Cognitive
      performance was measured repeatedly over time using a computerized performance
      assessment battery. Treatment with AMPT or treatment with sleep deprivation
      increased sleepiness without producing marked or consistent deterioration in
      performance. By contrast, subjects who received both treatments reported greater
      sleepiness than those receiving either treatment alone, and developed severe
      cognitive impairment on a variety of tasks. These findings, along with previous
      evidence that catecholamine-enhancing drugs improve performance in sleep-deprived
      individuals, support the view that decline in cognitive performance during sleep
      deprivation may be mediated by brain catecholamines.

PMID- 1356025
TI  - Low-dose bromocriptine in neuroleptic-resistant schizophrenia: a pilot study.

PMID- 1356026
TI  - 3-substituted-1,2-benzisoxazoles: novel antipsychotic agents.
AB  - A series of 3-substituted-6-fluoro-1,2-benzisoxazoles (II) was synthesized and
      evaluated for potential antipsychotic activity. Many of the compounds displayed
      potent antipsychotic-like activity in the apomorphine induced climbing in mice
      (CMA) or spiroperidol binding assays, and compound 42 (HRP 392, 1-[3-(6-fluoro
      1,2-benzisoxazol-3-yl)propyl]-4-(2-methoxyphenyl) piperazine) was selected for
      more detailed antipsychotic evaluation in a battery of preclinical assays. The
      results of these studies suggests that 42 is a potential antipsychotic drug with
      less propensity for EPS than some standard neuroleptics in monkeys. The compound
      was advanced for toxicological evaluation.

PMID- 1356027
TI  - Methionine-enkephalin immunoreactivity in Merkel cell dense-core granules of nude
      mice sinus hair. A post-embedding immunogold electron-microscopic study.
AB  - The ultra-immunocytochemical technique applied in the present study revealed the
      occurrence of methionine-enkephalin (met-enkephalin)-like substance in the dense
      core granules of Merkel cells of nude mice sinus hair. Incubation of ultra-thin
      sections of sinus hair with met-enkephalin antisera conjugated with gold
      particles showed specific association of gold particles on the dense-core
      granules of the Merkel cells. Gold particles were heavily and specifically
      located on the dense-core granules as well as in the adjacent cytoplasm. Dense
      core granules of degenerating Merkel cells also exhibit met-enkephalin
      immunoreactivity. The nerve terminals associated with the Merkel cell did not
      show met-enkephalin immunoreactivity. Therefore, it is concluded that a met
      enkephalin-like substance is present and stored in nude mice Merkel cell dense
      core granules and it might act as a neurotransmitter or neuromodulator which
      could be involved in the functioning of the cell. Non-osmicated tissue should be
      used to locate this substance because of the possibility of cross-linkage of the
      amino acid sequence with osmium tetroxide.

PMID- 1356028
TI  - Possible induction of intercellular adhesion molecule-1 (ICAM-1) expression on
      endothelial cells by platelet-activating factor (PAF).
AB  - We demonstrated that PAF and IL-1 markedly induce ICAM-1 expression on
      endothelial cells. These findings suggest that PAF not only modulates
      inflammation by the attraction and activation of eosinophils or by platelet
      activation, but also intensifies such phenomena by induction of ICAM-1 expression
      on endothelial cells.

PMID- 1356029
TI  - Current issues related to the transmission of blood-borne pathogens.

PMID- 1356030
TI  - Effects of Taxotere and taxol on in vitro colony formation of freshly explanted
      human tumor cells.
AB  - Taxotere (RP 56976, NSC 628503) is a new semisynthetic analog of taxol (NSC
      125973) with promising antitumor activity in a variety of preclinical screening
      systems. Clinical responses after treatment with taxol have been observed in
      ovarian cancer, breast, lung cancer and melanoma. Both agents act through
      induction of microtubule polymerization. We have studied and compared the
      antiproliferative action of Taxotere and taxol against a variety of freshly
      explanted human tumor specimens using an in vitro soft agar cloning system. Final
      concentrations of 0.025-10 micrograms/ml were used for both agents in short-term
      (1 h) or continuous (14 days) incubations. Taxotere was studied using a 1 h
      incubation in a total of 167 tumor specimens of which 85 (51%) were evaluable. At
      10 micrograms/ml, Taxotere inhibited 32 out of 78 (41%) specimens (colony
      formation less than or equal to 0.5 x control). Cytotoxicity of Taxotere was
      observed against breast, lung, ovarian, colorectal cancer and melanoma tumor
      colony forming units. For comparison, 227 specimens were exposed to taxol for 1
      h. At 10 micrograms/ml, 32 out of 97 evaluable specimens (33%) were significantly
      inhibited. Cytotoxicity was observed against breast, lung, ovarian, colorectal
      cancer and melanoma tumor colony forming units. In head-to-head comparisons, 29
      specimens were found more sensitive to Taxotere than taxol, while only 13 were
      more sensitive to taxol than to Taxotere. These data indicate that cross
      resistance between the two agents is incomplete and that on a concentration basis
      Taxotere is more cytotoxic than taxol in the majority of human primary tumor
      specimens evaluated.

PMID- 1356031
TI  - Histamine-2-receptor antagonists and gastric cancer: update and note on latency
      and covariates.
AB  - The relationship between treatment with histamine-2 (H2)-receptor antagonists
      (cimetidine and ranitidine) and subsequent risk of gastric cancer was analyzed
      with data of a case-control study conducted in northern Italy between 1983 and
      1991 on 628 incident cases of gastric cancer and 1776 control subjects who had
      been hospitalized for acute, nonneoplastic, non-digestive-tract disorders, with a
      specific focus on time-risk relationships and analysis of covariates. Previous
      use of H2-receptor antagonists was reported by 45 (7.2%) cancer patients and 68
      (3.8%) control subjects; the corresponding multivariate relative risk (RR) was
      2.1 (95% confidence interval [CI] 1.4-3.8). A significantly elevated risk,
      however, was evident only among individuals (27 patients and 23 control subjects)
      who had started using the drug less than 5 yr before diagnosis (RR 3.8, 95% CI
      2.1-6.1). The risk estimate declined to 2.1 (95% CI 1.0-4.2) for use starting 5-9
      yr before diagnosis and to 0.4 (95% CI 0.2-1.2) for use starting greater than or
      equal to 10 yr before diagnosis. When the relationship between use of H2-receptor
      antagonists and gastric cancer risk was examined across strata of sex, age, and
      other selected covariates (educational level, tobacco use, and alcohol and coffee
      consumption), all RRs were greater than unity for use starting less than 5 yr
      before diagnosis, but there was no evidence of any consistent association for use
      starting in the more distant past. Furthermore, there was no evidence of
      heterogeneity in the RRs for H2-receptor antagonist use and gastric cancer across
      strata of the covariates examined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356032
TI  - Alpha-linolenic acid and metabolism of cholesterol and long-chain fatty acids.
AB  - Animal studies have demonstrated that dietary 18:3n-3 reduces 20:4n-6 content in
      plasma and tissue lipids. At megadose levels of 18:3n-3, the reduction in
      phospholipid 20:4n-6 is brought about by a combination of inhibition of
      desaturase activities and redistribution of 20:4n-6 from phospholipids to neutral
      lipid pools. The shifting phenomenon is not apparent when the dietary level of
      18:3n-3 is low. Dietary 18:3n-3 reduces cholesterol levels in blood and liver
      tissue; however, the mechanism by which this effect is mediated is not known.
      Further studies are warranted to investigate the role of dietary 18:3n-3 on
      cholesterol biosynthesis, storage, and mobilization into and from the tissues and
      on the secretion of cholesterol into bile. The effect of the ratio of dietary
      18:2n-6 to SFA as a determinant of 20:4n-6 and lipid-lowering effects should be
      further explored in human subjects. It is important to elucidate whether dietary
      18:3n-3 interacts with other nutrients to modulate the parameters implicated in
      the pathogenic processes. The optimum level of dietary 18:3n-3 required to obtain
      health beneficial effects needs to be determined. Specific effects of dietary
      18:3n-3 on low- and high-density lipoprotein cholesterol levels also deserves
      further investigation before any recommendation to achieve health benefits can be
      made.

PMID- 1356033
TI  - Alpha-linolenic acid and prostaglandin synthesis.

PMID- 1356034
TI  - Human metabolic studies with deuterated alpha-linolenic acid.

PMID- 1356035
TI  - Alpha-linolenic acid and immune response.

PMID- 1356036
TI  - Alpha-linolenic acid metabolism in fish.

PMID- 1356037
TI  - Alpha-linolenic acid metabolism: the chicken and the egg.

PMID- 1356038
TI  - Postural stability, tardive dyskinesia and developmental disability.
AB  - The postural stability of four adult populations was examined through force
      platform methods. The four groups were classified as: (1) developmentally
      disabled (severely and profoundly mentally retarded) with tardive dyskinesia; (2)
      developmentally disabled but with no history of neuroleptic medication; (3)
      tardive dyskinetic but of normal intelligence; and (4) a normal and healthy
      control group. Postural conditions included standing still with arms at side,
      standing still with one arm or both arms parallel to the ground, and standing
      still while swinging both arms in the sagittal plane. The findings showed that
      both tardive dyskinetic and/or developmentally disabled groups exhibited greater
      sway and variability in centre of pressure motion in contrast to the control
      group. The developmentally disabled with tardive dyskinesia group also exhibited
      a strong tendency to produce a different form to the postural sway strategy in
      that they produced rhythmical centre of pressure motions during stance that were,
      to some degree, task dependent. The findings show that the combined effects of
      developmental disability and tardive dyskinesia produce qualitatively and
      quantitatively different features in postural stability patterns. The data
      suggest that postural stability measures may be a useful index to assess tardive
      dyskinesia.

PMID- 1356039
TI  - A fatal case of ischaemic colitis following long-term use of neuroleptic
      medication.

PMID- 1356040
TI  - Recurrent neuroleptic malignant syndrome in a man with mild mental handicap.
AB  - A case of recurrent neuroleptic malignant syndrome (NMS) occurring in a 29-year
      old man with mild mental handicap and a superadded psychotic disorder is
      described. The case illustrates a number of unusual features such as recurrent
      episodes and resolution with administration of intravenous Procyclidine. The
      possibility of NMS occurring in people with mental handicap, who have a high
      level of neuroleptic drug prescription, must be borne in mind.

PMID- 1356041
TI  - Plasmid mediated metal and antibiotic resistance in marine Pseudomonas.
AB  - Pseudomonas sp isolated from the Bay of Bengal (Madras coast) contained a single
      large plasmid (pMR1) of 146 kb. Plasmid curing was not successful with mitomycin
      C, sodium dodecyl sulfate, acridine orange, nalidixic acid or heat. Transfer of
      mercury resistance from marine Pseudomonas to Escherichia coli occurred during
      mixed culture incubation in liquid broth at 10(-4) to 10(-5) ml(-1). However,
      transconjugants lacked the plasmid pMR1 and lost their ability to resist mercury.
      Transformation of pMR1 into E. coli competent cells was successful; however, the
      efficiency of transformation (1.49 x 10(2)Hgr transformants microsgm-1 pMR1 DNA)
      was low. E. coli transformants containing the plasmid pMR1 conferred inducible
      resistance to mercury, arsenic and cadmium compounds similar to the parental
      strain, but with increased expression. The mercury resistant transformants
      exhibited mercury volatilization activity. A correlation existed between metal
      and antibiotic resistance in the plasmid pMR1.

PMID- 1356042
TI  - Vertebrate axis formation.
AB  - Molecular understanding of axis formation has recently taken a great leap forward
      with the identification and functional characterization of regulatory genes that
      appear to act at the top of the hierarchy leading to positional specification in
      the vertebrate. Analysis of these genes, which encode peptide growth factors and
      their receptors as well as transcription factors, is disclosing principles of
      early cell fate specification that are common to all vertebrates.

PMID- 1356043
TI  - Abuse of neuroleptic drugs?

PMID- 1356044
TI  - Workshop on Trophic Factors in the Peripheral Nervous System. Capri, October
      1991.

PMID- 1356045
TI  - Acute myopathy with selective degeneration of myosin filaments following status
      asthmaticus treated with methylprednisolone and vecuronium.
AB  - We report two cases of severe, acute myopathy with selective degeneration of
      myosin filaments in asthmatics who developed respiratory failure with hypercapnia
      and acidosis requiring endotracheal intubation, administration of vecuronium and
      prolonged ventilatory support. Hypoxia was documented in one case and probably
      present in the other. Both patients received prolonged treatment with high doses
      of intravenous methylprednisolone. Flaccid quadriparesis was noted after
      discontinuation of vecuronium. Muscle biopsy showed nonspecific myopathic changes
      on light microscopy. Electron microscopy revealed selective loss of myosin
      filaments in many fibers. Recovery occurred within 2 months with supportive
      treatment. This entity is probably related to a combination of high doses of
      corticosteroids, vecuronium administration and metabolic abnormalities associated
      with respiratory failure.

PMID- 1356046
TI  - Report on the 12th ENMC sponsored international workshop--the "limb-girdle"
      muscular dystrophies.

PMID- 1356047
TI  - Steroids in Duchenne muscular dystrophy.

PMID- 1356048
TI  - Criteria for diagnosis of familial amyotrophic lateral sclerosis. European FALS
      Collaborative Group.
AB  - Clinical criteria for the diagnosis of motor neuron disease, agreed at the
      inaugural meeting of the European Familial Amyotrophic Lateral Sclerosis
      Collaborative Group, are described. The criteria are derived from those developed
      for the study of sporadic amyotrophic lateral sclerosis, and allow the inclusion
      of certain recognized clinical sub-types of familial amyotrophic lateral
      sclerosis. They will require testing for consistency and sensitivity.

PMID- 1356049
TI  - Long regions of homologous DNA are incorporated into the tobacco plastid genome
      by transformation.
AB  - We investigated the size of flanking DNA incorporated into the tobacco plastid
      genome alongside a selectable antibiotic resistance mutation. The results showed
      that integration of a long uninterrupted region of homologous DNA, rather than of
      small fragments as previously thought, is the more likely event in plastid
      transformation of land plants. Transforming plasmid pJS75 contains a 6.2-kb DNA
      fragment from the inverted repeat region of the tobacco plastid genome. A
      spectinomycin resistance mutation is encoded in the gene of the 16S rRNA and, 3.2
      kb away, a streptomycin resistance mutation is encoded in exon II of the
      ribosomal protein gene rps12. Transplastomic lines were obtained after
      introduction of pJS75 DNA into leaf cells by the biolistic process and selection
      for the spectinomycin resistance marker. Homologous replacement of resident wild
      type sequences resulted in integration of all, or almost all, of the 6.2-kb
      plastid DNA sequence from pJS75. Plasmid pJS75, which contains engineered cloning
      sites between two selectable markers, can be used as a plastid insertion vector.

PMID- 1356050
TI  - Degradation products of the mRNA encoding the small subunit of ribulose-1,5
      bisphosphate carboxylase in soybean and transgenic petunia.
AB  - The degradation of a soybean ribulose-1,5-bisphosphate carboxylase small subunit
      RNA, SRS4, was investigated in soybean seedlings and in petunia plants
      transformed with an SRS4 gene construct. Polyacrylamide RNA gel blot, primer
      extension, and S1 nuclease analyses were used to identify and map fragments of
      the SRS4 mRNA generated in vivo. We showed that SRS4 mRNA is degraded to a
      characteristic set of fragments in soybean and transgenic petunia and that
      degradation is not dependent on position of insertion of the gene construct
      within the genome, on the expression level of the SRS4 mRNA, or on the rbcS
      promoter. Degradation products lacked poly(A) tails and fractionated with poly(A)
      depleted RNA on oligo(dT)-sepharose columns. These products pelleted with
      polysomes and were released from polysomes prepared with EDTA. Sequences at the
      5' end of the SRS4 mRNA were more stable than those at the 3' end of the mRNA.
      Three models for SRS4 mRNA degradation involving endonucleolytic and
      exonucleolytic degradation were presented to explain the origin of the 5'
      proximal fragments.

PMID- 1356051
TI  - A novel variant of transthyretin (prealbumin), Thr119 to Met, associated with
      increased thyroxine binding.
AB  - A group of patients with prealbumin associated hyperthyroxinemia possess a common
      single base substitution in the fourth exon of their transthyretin gene. This
      cytosine to thymine substitution occurs in the codon for residue 119 and results
      in the predicted replacement of a threonine residue with a methionine at this
      position. A new NcoI restriction endonuclease cleavage site is created by the
      point mutation and can be detected by a rapid and simple assay based on the
      polymerase chain reaction. This variant transthyretin is inherited in an
      autosomal dominant manner and is apparently not amyloidogenic but is associated
      with increased thyroxine binding. As healthy heterozygous individuals have normal
      serum thyroxine concentrations, the hyperthyroxinemia sometimes found may not be
      primarily due to the variant.

PMID- 1356052
TI  - Thyroid-stimulating antibodies and thyroid stimulation-blocking antibodies during
      the pregnancy and postpartum period: a case report.
AB  - This report describes a unique pattern of changes in thyroid function and thyroid
      antibodies in a woman during the course of two pregnancies and two postpartum
      periods. A 25-year-old woman developed hypothyroidism in the postpartum period
      after the delivery of her first child. She was found to have potent thyroid
      stimulation-blocking antibodies (TSBAb) in the serum. One year later, she became
      pregnant again, and during the pregnancy, TSBAb had decreased to an undetectable
      level. She gave birth to the second healthy child and developed postpartum
      thyrotoxicosis, probably due to destruction of the thyroid gland, which gradually
      resolved. In this postpartum period, serum TSBAb levels increased. Eight months
      postpartum, she developed what appeared to be Graves' disease with an elevated
      123I-thyroid uptake. Serum thyroid-stimulating antibodies (TSAb) were found at
      that time, and the TSBAb had disappeared from her serum.

PMID- 1356053
TI  - Chromogranin A as tumor marker in medullary thyroid carcinoma.
AB  - We measured plasma levels of chromogranin A (CgA) and calcitonin (CT) in 61
      patients with surgically confirmed medullary thyroid carcinoma (MTC). CT was
      elevated in 46 patients, whereas CgA was elevated in 14 patients. Plasma levels
      of CgA and CT were moderately correlated (r = 0.87), but CgA became elevated in
      most patients only in advanced disease. Patients with high plasma CT values
      (greater than 10 micrograms/L) also had elevated CgA in 83% of cases. An elevated
      plasma CgA level despite normal CT levels was found in only 1 patient. In 8 MTC
      patients with moderately elevated basal CT levels, pentagastrin as a secretagogue
      usually was not able to release detectable amounts of CgA from MTC tissue. In 2
      MTC patients, i.v. catheter sampling gave sharp gradients for CT concentrations
      (greater than 2.7-fold peak to peripheral ratios) and, therefore, precise MTC
      tissue localization, whereas no gradients were demonstrable for CgA (less than
      1.2-fold). One patient with MTC and elevated CgA reached normal CgA plasma levels
      within 8 days after thyroidectomy. In metastatic tissue from 8 patients with MTC,
      CgA and CT were detectable immunohistologically in all cases, but plasma CgA was
      elevated only in 2 and CT in 7 of them. Plasma CgA levels in patients with MTC
      usually became elevated only in advanced disease and were not able to detect
      early disease stages, were correlated with CT levels, were not useful in
      stimulation tests or venous localization studies, and probably resulted from the
      release from MTC tissue as the major tissue source, as shown in the sporadic
      cases.

PMID- 1356054
TI  - Thyroid growth immunoglobulins in feline hyperthyroidism.
AB  - Feline hyperthyroidism bears a strong clinical and pathologic resemblance to
      toxic nodular goiter in humans. To evaluate whether the observed thyroid growth
      might be due to circulating thyroid antibodies, as has been postulated in humans,
      we studied the effect of purified immunoglobulin (Ig) G preparations on a rat
      thyroid follicular (FRTL-5) cell line. When compared with control, hyperthyroid
      cat IgG caused significantly increased [3H]-thymidine (Tdr) incorporation into
      DNA (p less than 0.02) and stimulated cellular proliferation 15-fold. Stimulation
      of 3H-Tdr incorporation tended to be biphasic and could be inhibited completely
      by a potent, specific TSH receptor blocking antibody. Hyperthyroid cat IgG also
      significantly inhibited 125I-bTSH binding to porcine thyroid membranes, an effect
      that could be reproduced using electrophoretically pure IgG and normal cat
      thyroid membranes. Unlike its effect on growth, hyperthyroid cat IgG did not
      stimulate intracellular cAMP, and there was no correlation between thyroid
      function in vivo and IgG growth-promoting activity in vitro. These data suggest
      that elevated titers of thyroid growth IgGs, probably acting through the TSH
      receptor, are present in feline hyperthyroidism and may play a role in goiter
      formation. Unlike growth, the thyroid hyperfunction observed is not IgG
      dependent. Further study of feline hyperthyroidism may contribute important
      insights into human nodular goiter and into the mediation of thyroid growth in
      general.

PMID- 1356055
TI  - Toxic Graves' disease with thyroid hemiagenesis: diagnosis using thyroid
      stimulating immunoglobulin measurements.
AB  - Two patients with hemiagenesis of the thyroid gland experienced thyrotoxicosis.
      They constituted 1.1% of our clinic's total population of 178 thyrotoxic patients
      treated in the years 1986-1990 and 1.7% of 120 patients with thyrotoxic Graves'
      disease encountered during that period. The diagnosis was made on the basis of
      unilateral homogeneous 99mTcO4 uptake on thyroid scan, no change in the scan
      after both cessation of propylthiouracil (PTU) treatment for 4 days and TSH
      stimulation test, and high thyroid-stimulating immunoglobulin (TSI) levels. Both
      patients went into remission after PTU treatment, and TSI levels returned to
      normal. The diagnosis of toxic Graves' disease with thyroid hemiagenesis was,
      therefore, made. This combination is rare but important to recognize because
      treatment as well as prognosis might be different from that of toxic adenoma.

PMID- 1356056
TI  - Fetal and neonatal hyperthyroidism and hypothyroidism due to maternal TSH
      receptor antibodies.
AB  - Autoimmune thyroid disease is a generic term that includes Graves' disease and
      Hashimoto's thyroiditis. In the former, there is overactivity of the thyroid due
      to the action of a thyroid-stimulating antibody (TSAb). Pathogenesis of
      Hashimoto's thyroiditis is largely cell-mediated immune destruction of the
      thyroid. Nonetheless, there may be either a goiter or an atrophic gland. There is
      evidence that in some patients the lack of goiter is associated with the presence
      in the blood of an antibody that inhibits the binding of TSH to its receptor.
      This TSH-binding inhibiting antibody (TBIAb), therefore, prevents TSH from
      stimulating the thyroid and constitutes an acceptable explanation for an
      agoitrous state. Collectively, TSAb and TBIAb, both of which are IgG, are known
      as TSH receptor antibodies (TRAb).

PMID- 1356057
TI  - Analysis of chimerism after bone marrow transplantation using specific
      oligonucleotide probes.
AB  - DNA hybridization with synthetic oligonucleotide probes was used to follow 18
      leukemia patients who received bone marrow transplantation from HLA-identical
      siblings. Five oligomers complementary to the tandem repetitive sequences of
      different hypervariable regions of human DNA were designed to produce simple
      restriction fragment length polymorphism patterns. Each probe hybridized to one
      or two bands in Hinf I-digested genomic DNA. Combined use of these probes enabled
      us to distinguish all sibling pairs. DNA analysis early post-transplant (15 days)
      detected donor-specific fragments in 14 of 18 subjects; two patients had a
      combination of recipient and donor fragments. Later post-transplant, (102-15
      days), one of these two showed only recipient-specific fragments, and the other
      donor-specific fragments. These data are in accord with other markers of
      engraftment including cytogenetics and red blood cell phenotyping.

PMID- 1356058
TI  - Is there a disease-modifying drug for juvenile chronic arthritis?

PMID- 1356059
TI  - Epidermal growth factor selectively enhances NMDA receptor-mediated increase of
      intracellular Ca2+ concentration in rat hippocampal neurons.
AB  - We have previously reported that recombinant human epidermal growth factor (hEGF)
      facilitates induction of hippocampal long-term potentiation (LTP). In order to
      clarify the mechanism underlying the LTP-facilitating effect of hEGF, the
      influence of hEGF on intracellular Ca2+ concentration ([Ca2+]i) of hippocampal
      neurons was investigated using dissociated cell cultures. Changes in [Ca2+]i were
      measured by microfluorometrically monitoring the fluorescence intensities from
      individual neurons loaded with fura-2. Application of hEGF (0.6-20 ng/ml) alone
      did not affect the basal level of [Ca2+]i in cultured hippocampal neurons, but
      significantly enhanced the [Ca2+]i increase induced by L-glutamate (3 x 10(-6)
      M). The N-methyl-D-aspartate (NMDA) (10(-5) and 3 x 10(-5) M)-induced [Ca2+]i
      increase was also enhanced by hEGF, but the quisqualate (10(-7) and 3 x 10(-7) M)
      induced response was not affected by the presence of hEGF. These results suggest
      that hEGF selectively enhances the NMDA receptor-mediated responses in
      hippocampal neurons. This action of hEGF may underlie the facilitation of
      hippocampal LTP.

PMID- 1356060
TI  - Immunohistochemical markers in rat cortex: co-localization of calretinin and
      calbindin-D28k with neuropeptides and GABA.
AB  - Calretinin and calbindin-D28k are two calcium-binding proteins which are present
      in separate populations of interneurons in cerebral cortex and hippocampus. To
      identify these cells with the populations expressing different transmitters, two
      colour immunofluorescence was done with antibodies against the calcium-binding
      proteins plus antibodies against vasoactive intestinal peptide (VIP),
      somatostatin (SRIF), or gamma-aminobutyric acid (GABA). In neocortex, calretinin
      is partially co-localized with VIP (especially in the deeper layers) and is not
      co-localized with SRIF. Calbindin is largely co-localized with SRIF, and not with
      VIP. Both calretinin and calbindin are partially co-localized with GABA. In
      piriform and entorhinal cortex, the patterns resemble those in neocortex. In
      hippocampus, preliminary data indicate greater heterogeneity, especially in the
      ventral part; at least a few double-positive cells are present for every
      combination of calcium-binding protein and neuropeptide. These results expand the
      known diversity of local-circuit neurons in cortical regions.

PMID- 1356061
TI  - Low levels of somatostatin-like immunoreactivity in neocortex resected from
      presumed seizure foci in epileptic patients.
AB  - The concentration of somatostatin-like immunoreactivity (SS-LI) was determined by
      radioimmunoassay in neocortical tissue resected from 20 patients with
      pharmacologically intractable complex partial seizures. Most resections included
      either the anterior temporal pole neocortex (15 cases) or cingulate gyrus
      neocortex (3 cases). The concentration of SS-LI was lowest in cortical tissue
      immediately adjacent to cortical tumors. Preoperative electrical recordings
      suggested that this tissue was the seizure focus. In vitro recordings showed that
      this tissue also exhibited abnormal hyperexcitable synaptic responses. Higher
      levels of SS-LI, similar to normal values previously reported in human cortex,
      were present in non-focal temporal neocortical tissue (resected from patients in
      whom the seizure focus was in the ipsilateral hippocampus) in which no
      hyperexcitable synaptic activity was present in vitro. The functional loss of
      inhibitory transmitters suggested by the low SS-LI levels might provide a
      theoretical basis for the hyperexcitability observed in vivo and in vitro.

PMID- 1356063
TI  - Immunohistochemical markers in rat brain: colocalization of calretinin and
      calbindin-D28k with tyrosine hydroxylase.
AB  - Many dopaminergic cells of the substantia nigra are known to contain the calcium
      binding proteins calretinin and calbindin-D28k. Catecholaminergic cell groups
      throughout the rat brain were therefore examined by two-colour immunofluorescence
      to determine whether they too contained these calcium-binding proteins as well as
      tyrosine hydroxylase (TH). Some TH+ cell groups are mostly positive for both
      calretinin and calbindin, notably in the ventral tegmental area, the
      interfascicular nucleus, and parts of the substantia nigra. Other TH+ cell groups
      in the midbrain, hindbrain and hypothalamus are very diverse; different cell
      groups are positive for calretinin, or calbindin, or both, or neither. In the
      olfactory bulb, entirely separate sets of periglomerular cells are positive for
      TH, calretinin and calbindin. However, there is considerable heterogeneity in
      calcium-binding protein expression within most cell groups, even in the
      substantia nigra. This could be a sign that calcium-binding proteins are
      regulated according to aspects of neuronal activity.

PMID- 1356062
TI  - GABAergic synaptic transmission in projections from the basal forebrain and
      hippocampal formation to the amygdala: an in vivo iontophoretic study.
AB  - We recorded extracellular responses from rat amygdaloid neurons in vivo after
      electrical stimulation of the basal forebrain and hippocampal formation.
      Iontophoretic application of the GABAA receptor antagonist, bicuculline, lead to
      the appearance of short latency evoked bursts after stimulation of either region.
      This occurred whether the baseline response was inhibitory or excitatory.
      Bicuculline only affected an early phase of inhibition, leaving a longer latency,
      longer duration phase unchanged or even increased. By contrast, the GABAB
      receptor antagonist, phaclofen, never produced such short latency evoked bursts.
      Both bicuculline and phaclofen increased the spontaneous rate of firing of
      amygdaloid neurons. The excitatory burst response to hippocampal formation
      stimulation of an amygdaloid candidate inhibitory neuron was blocked by CNQX (an
      antagonist of the AMPA subtype of glutamate receptor). Based on these and prior
      studies, it seems likely that the effects of hippocampal formation stimulation
      are mediated by feed-forward inhibition, in which GABAergic amygdaloid inhibitory
      neurons are excited by glutamatergic projections from the hippocampal formation.
      The effects of basal forebrain stimulation may be mediated by both feed-forward
      inhibition and direct, GABAergic inhibition.

PMID- 1356064
TI  - Food intake of lean and obese Zucker rats following ventricular infusions of
      adrenergic agonists.
AB  - The effect on food intake of adrenergic agonists administered into the third
      cerebral ventricle was studied in Zucker fatty and lean rats. The alpha 2
      agonist, clonidine, produced a larger dose-related increase in food intake in
      lean rats than in the fatty rats. Dose-response curves show similar sensitivity,
      but decreased responsiveness in the lean animal. The beta 2 adrenergic agonist,
      salbutamol, produced similar food effect in obese and lean rats reducing food
      intake in the lean rats at the highest dose (300 nmol), and in the fatty rats at
      the two highest doses. The effects were small in both groups. The beta 3 agonist,
      BRL 37344, ([4-(2-((2-hydroxy-2-(3-chlorophenyl)ethyl)amino)-propyl)-phenoxy
      acetate]) produced a larger dose-related decrease in food intake in the fatty rat
      than in the lean rats. Dose-response curves showed that sensitivity of beta
      receptors was similar, but the lean animals were less responsive. The beta
      adrenergic blocking drug propranolol blocked the anorectic effect of BRL 37344 in
      the fatty rat. These studies suggest that in the fatty rat, the alpha 2 receptor
      system is tonically more active and the beta 3 receptor system tonically less
      active, a relationship that would explain the hyperphagia and development of
      obesity in these animals.

PMID- 1356065
TI  - The infusion of an NMDA antagonist into perirhinal cortex suppresses amygdala
      kindled seizures.
AB  - The seizure-modulating role of N-methyl-D-aspartate (NMDA) receptors located in
      several limbic areas was investigated. Amygdala-kindled rats were microinfused
      with the selective NMDA-receptor antagonist 2-amino-5-phosphonovalerate (APV, 1
      microliter, 70 nmol) or artificial cerebrospinal fluid (ACSF) applied through a
      cannula located in either the amygdala or perirhinal, pyriform or deep
      prepyriform cortices. APV infused into the stimulation site raised the threshold
      for seizure generation. Surprisingly, APV infused into perirhinal cortex, but not
      into other regions, also dramatically suppressed behavioural seizures and
      afterdischarges (AD) elicited 5 min after the infusion. If stimulus intensities
      were markedly elevated however, the seizure suppression was overcome. This latter
      effect was reversible and repeatable, as seizures and AD were reliably reinstated
      when these animals were stimulated after infusion with ACSF. A similar effect,
      whereby perirhinal infusions blocked seizure activity, was also demonstrated in
      an animal kindled from the olfactory bulb and in one kindled from the perforant
      path. These results suggest that NMDA receptors located in the perirhinal cortex
      may play a major role in the modulation of AD activity elicited from more distal
      brain regions. Furthermore, activation of perirhinal cortex may be a critical
      requirement for the generation of amygdala-stimulated AD in the kindled animal.

PMID- 1356066
TI  - Effects of immunoneutralization of dynorphin1-17 and dynorphin1-8 on the activity
      of central dopaminergic neurons in the male rat.
AB  - The effects of administration of antibodies against dynorphin1-17 (DYN1-17-AB)
      and dynorphin1-8 (DYN1-8-AB) were examined on the activity of dopaminergic (DA)
      neurons comprising the nigrostriatal, mesolimbic, tuberoinfundibular and
      periventricular-hypophysial systems in the male rat brain. DA neuronal activity
      was estimated by measuring the concentration of the dopamine metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC) in brain (striatum, nucleus accumbens, median
      eminence) and pituitary regions (intermediate lobe) containing terminals of these
      neurons. The intracerebroventricular administration of either DYN1-17-AB or DYN1
      8-AB produced a time-related increase in the activity of tuberoinfundibular and
      periventricular-hypophysial DA neurons, but failed to alter the activity of
      nigrostriatal or mesolimbic DA neurons. The ability of both DYN1-17-AB and DYN1-8
      AB to enhance the activity of tuberoinfundibular and periventricular-hypophysial
      DA neurons was reversed by the kappa opioid agonist U-50,488. These results
      indicate that DYN1-17-AB and DYN1-8-AB, presumably by binding endogenous
      dynorphins, remove a tonic inhibitory action of these opioid peptides on
      tuberoinfundibular and periventricular-hypophysial DA neurons.

PMID- 1356067
TI  - Involvement of central dopamine and D1 receptors in stress-induced colonic motor
      alterations in rats.
AB  - The role of central versus peripheral influence of dopamine (DA) in the genesis
      of emotional stress (ES) induced by fear to receive electric footshocks on
      colonic motility was evaluated in rats equipped with implanted electrodes on the
      proximal colon. In control rats, the frequency of colonic spike bursts increased
      from 7.5 +/- 1.9 to 16.0 +/- 2.1 per 10 min when the rats were placed in a test
      box where they had previously received electric footshocks. This increase induced
      by ES was significantly p less than 0.05, reduced by previous ICV or IP
      administration of (+)SCH 23390 (a D1 receptor antagonist) at doses of 10 and 100
      micrograms/Kg, respectively. Although sulpiride (a D2 antagonist) injected ICV or
      IP at similar doses had no effect on the ES-induced increase in the frequency of
      colonic spike bursts. DA (100 micrograms/kg), and the selective D1 (SKF 38383) or
      D2 (quinpirole) receptor agonist injected ICV at a dose of 5 micrograms/kg also
      increased significantly by 48.7, 54.8, and 68.7%, respectively, the colonic spike
      burst frequency whereas they are inactive when injected IP at similar and higher
      doses. These results suggest that, in rats, (a) emotional stress stimulates
      colonic motility through the stimulation of dopaminergic neurons involving D1
      receptors and (b) exogenous activation of central D1 and D2 receptors similarly
      stimulate colonic motility by increasing the occurrence of colonic spike bursts.

PMID- 1356068
TI  - Influences of gender, gonadectomy, and estrous cycle on GABA/BZ receptors and
      benzodiazepine responses in rats.
AB  - Benzodiazepines (BZ) and steroid hormone derivatives can potentiate the
      inhibitory actions of GABA through interactions with the GABAA/BZ/chloride
      ionophore complex. The present study examines whether the in vivo hormone milieu
      of rats modulates GABA/BZ receptors and/or benzodiazepine responses. The
      influences of gender, estrous cycle, and the diminution of steroid levels on
      GABA/BZ receptors and BZ anticonvulsant responses were tested by comparing these
      parameters in groups of intact male, intact female, orchidectomized, and
      ovariectomized rats. The hormonal milieu appears to modulate the GABA recognition
      site and possibly GABA-related responses in rats. This is evidenced by the
      decrease in cortical GABAA receptor affinity seen in females compared with other
      hormone groups and the gender-related difference observed in susceptibility to
      seizures induced by the GABA antagonist bicuculline. In cycling females, high
      circulating levels of progesterone were correlated with heightened seizure
      thresholds, suggesting that progestins serve a protective role in the control of
      seizure activity. Although a gender-related difference in cortical BZ binding
      affinity was observed, BZ receptor parameters in several other brain areas and BZ
      anticonvulsant responses were unaffected by physiological fluctuations in gonadal
      hormones.

PMID- 1356069
TI  - NMDA receptors mediate the behavioral effects of amphetamine infused into the
      nucleus accumbens.
AB  - The present experiments examined glutamate-dopamine interactions within the
      nucleus accumbens in rats. It has been hypothesized that dopaminergic nerve
      terminals exert a modulatory influence on glutamate-mediated signals from
      corticolimbic areas. In the present studies, the effect of the selective NMDA (n
      methyl-d-aspartate) antagonist AP5 (2-amino-5-phosphonopentanoic acid) on
      amphetamine-mediated behaviors was observed. In two behavioral paradigms, AP5 (0,
      0.05, 0.5, 1.0 micrograms bilaterally) was microinjected immediately prior to
      amphetamine (5 micrograms bilaterally) in the nucleus accumbens. In the first
      experiment, the influence of AP5 on amphetamine-induced motor activity was
      examined. AP5 dose-dependently reduced the effectiveness of amphetamine in
      stimulating motor behavior. AP5 alone, paradoxically, tended to increase motor
      activity. In the second experiment, the effects of AP5 on amphetamine-potentiated
      responding (lever pressing) for conditioned reward (CR) were investigated.
      Normally, when amphetamine is infused into the nucleus accumbens, a marked
      potentiation of CR responding occurs. Prior infusion of AP5 also attenuated this
      behavioral effect of amphetamine. The results demonstrate that NMDA receptors
      within the nucleus accumbens mediate the behavioral consequences of increased
      dopamine release. They provide additional evidence for the involvement of limbic
      striatal connections in the activating and reinforcing effects of psychostimulant
      drugs.

PMID- 1356070
TI  - [The effect of BL 343 Ac, a beta-adrenolytic, on the cervical ganglion].
AB  - The activity of the newly synthetized substance BL 343 Ac (propyl-3-acetyl-4[/2
      hydroxy-3-isopropyl amino/propoxy] carbanylate of hydrochloride), a beta 1
      adrenolytic with sympathomimetic activity was investigated by means of the
      electrophysiological method of sucrose gap. Its effect on the membrane potential
      of a population of neurons of the superior cervical ganglion (GCS) of the cat was
      analyzed with the aim to contribute to the knowledge on the selectivity of action
      of this substance. In the GCS of the cat, which contains predominantly beta 2
      adrenoceptors, BL 343 Ac given in concentrations from 0.01 to 50 mumol.l-1 and
      after single application into the superfusion stream close to the ganglion in
      doses from 0.01 to 1,000 nmol did not induce an unequivocal change in the
      membrane potential or a response comparable to that elicited by isoprenaline. No
      blocking effect of the substance BL 343 Ac (0.01-50 mumol.l-1) was observed on
      isoprenaline induced depolarization of the cat GCS. The obtained results indicate
      that BL 343 Ac fails to exert either beta 2-adrenomimetic or beta 2-adrenolytic
      effect on the GCS of the cat. (Fig. 2, Ref. 11.)

PMID- 1356072
TI  - [Multidrug resistance and the P-glycoprotein].
AB  - A survey is presented on the information concerning the nature and molecular
      mechanism of multi drug resistance, a phenomenon involving the resistance of
      tumor cells to different types of chemotherapeutic agents. P-glycoprotein is by
      its enzymatic activity directly responsible for expelling xenobiotics from the
      intracellular space and thus also for the development of MDR. Its detection
      provided new possibilities for causal studies of this type of resistance as well
      as for its in vitro modelling. In the presented survey, the function of P
      glycoprotein is characterized also in cells of normal nontumorous tissue.

PMID- 1356073
TI  - Advances in health care, highway safety reducing number of organ donors, MD says.

PMID- 1356071
TI  - [The delta F508 mutation which causes cystic fibrosis and its association with
      closely linked DNA polymorphisms in the Slovak population].
AB  - Linkage relationships between DNA polymorphism metH/TaqI as well as KM19/PstI and
      the mutation causing cystic fibrosis (CF) were analyzed in 48 families from
      Slovakia with th occurrence of CF. The polymorphism metH/TaqI did not show
      linkage disequilibrium with CF mutation. A pronounced allelic association was
      however found between CF mutation and KM19/PstI polymorphism. Of the 83 CF
      chromosomes analyzed, the given mutation was associated with the 6.6 kb allele in
      82% of cases, while the rate of this allele in chromosomes without the mutation
      amounts only to 24%. The value of the standardized disequilibrium coefficient SCD
      = 0.58. Delta F508 deletion was addressly studied in 25 patients (i.e. 50 CF
      chromosomes). Of the 50 CF mutations, the given deletion was in 64% (32), while
      the remaining 36% (18) of mutations were of other, closely not identified types.
      Delta F508 deletion is in marked allelic association with the 6.6 kb allele of
      KM19/PstI polymorphism (SCD = 0.68). Between the given allele of KM19/PstI
      polymorphism and CF mutation no other allelic association was found but with
      delta F508. (Tab. 6, Fig. 1, Ref. 18).

PMID- 1356074
TI  - Medication-induced systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease affecting
      a variety of tissues and organs. The diagnosis of SLE can be made only after
      several related illnesses are considered and ruled out. The etiology of SLE is
      unclear, but hormonal factors, environmental toxins, infectious viruses, genetic
      predisposition, and certain medications have all been considered risk factors.
      Idiopathic SLE is seen predominantly in young women, with a female:male ratio of
      approximately 10:1. Each patient is unique and may suffer from a variety of signs
      and symptoms. The disease is highly unpredictable, and most patients experience
      flare-ups or fluctuations. The epidemiologic characteristics of medication
      induced SLE (MI-SLE) are different from those of idiopathic SLE. Musculoskeletal
      symptoms predominate the clinical presentation of MI-SLE, while renal and central
      nervous system involvement is rare or absent. Moreover, a greater percentage of
      caucasian patients with no female predominance is evidenced in MI-SLE. Several
      medications can produce positive results on an antinuclear antibody test with or
      without evidence of clinical lupus. Hydralazine and procainamide are the most
      commonly recognized medications for inducing SLE. The onset of procainamide- and
      hydralazine-induced SLE occurs after 50 years of age, which is directly related
      to the age of the population using these medications. Estrogen-containing oral
      contraceptives and ibuprofen can exacerbate the symptoms of idiopathic SLE.
      Clinical judgment dictates the importance of careful patient monitoring and
      selection of therapy.

PMID- 1356075
TI  - CLIP-170 links endocytic vesicles to microtubules.
AB  - Binding of endocytic carrier vesicles to microtubules depends on the microtubule
      binding protein CLIP-170 in vitro. In vivo, CLIP-170 colocalizes with a subset of
      transferrin receptor-positive endocytic structures and, more extensively, with
      endosomal tubules induced by brefeldin A. The structure of CLIP-170 has been
      analyzed by cloning its cDNA. The predicted non-helical C- and N-terminal domains
      of the homodimeric protein are connected by a long coiled-coil domain. We have
      identified a novel motif present in a tandem repeat in the N-terminal domain of
      CLIP-170 that is involved in binding to microtubules. This motif is also found in
      the Drosophila Glued and yeast BIK1 proteins. These features, together with its
      very elongated structure, suggest that CLIP-170 belongs to a novel class of
      proteins, cytoplasmic linker proteins (CLIPs), mediating interactions of
      organelles with microtubules.

PMID- 1356076
TI  - Altered cell cycle arrest and gene amplification potential accompany loss of wild
      type p53.
AB  - Gene amplification occurs at high frequency in transformed cells (10(-3)-10(-5)),
      but is undetectable in normal diploid fibroblasts (less than 10(-9)). This study
      examines whether alterations of one or both p53 alleles were sufficient to allow
      gene amplification to occur. Cells retaining one wild-type p53 allele mimicked
      the behavior of primary diploid cells: they arrested growth in the presence of
      drug and failed to demonstrate amplification. Cells losing the second p53 allele
      failed to arrest when placed in drug and displayed the ability to amplify at a
      high frequency. Thus, loss of wild-type p53 may lead to amplification, possibly
      caused by changes in cell cycle progression. Other determinants can by-pass this
      p53 function, however, since tumor cells with wild-type p53 have the ability to
      amplify genes.

PMID- 1356077
TI  - V(D)J recombination: broken DNA molecules with covalently sealed (hairpin) coding
      ends in scid mouse thymocytes.
AB  - Lymphoid cells from scid mice initiate V(D)J recombination normally but have a
      severely reduced ability to join coding segments. Thymocytes from scid mice
      contain broken DNA molecules at the TCR delta locus that have coding ends, as
      well as molecules with signal ends, whereas in normal mice we previously detected
      only signal ends. Remarkably, these coding (but not signal) ends are sealed into
      hairpin structures. The formation of hairpins at coding ends may be a universal,
      early step in V(D)J recombination; this would provide a simple explanation for
      the origin of P nucleotides in coding joints. These findings may shed light on
      the mechanism of cleavage and suggest a possible role for the scid factor.

PMID- 1356079
TI  - Novel mitochondrial genomes in Brassica napus somatic hybrids.
AB  - The mitochondrial genomes of nine male-fertile and two Ogura cytoplasmic male
      sterile (cms) Brassica napus somatic hybrids were probed with 46 mitochondrial
      DNA fragments. The distribution of information obtained from each fusion partner
      was not random. Several regions, including the coxI gene and a major
      recombination repeat sequence, were always derived from the Brassica campestris
      fusion partner, and some regions were always derived from the Ogura mitochondrial
      genome. Novel fragments occurred in seven distinct regions. Some of the
      rearrangement breakpoints were located near the evolutionary breakpoints relating
      the mitochondrial genomes of the Brassica species. The sizes of the mitochondrial
      genomes in the somatic hybrids ranged from 224.8 to 285.3 kb. A direct
      correlation between a specific gene and the cms phenotype was not observed;
      however, a possible cms-associated region was identified. It corresponds to a
      region that was identified through analysis of fertile revertants from a cms B.
      napus cybrid.

PMID- 1356078
TI  - Thialysine-resistant mutants and uptake of lysine in Schizosaccharomyces pombe.
AB  - Mutants defective in lysine transport were isolated and characterized. After UV
      mutagenesis colonies resistant to thialysine, a toxic analogue of lysine, were
      isolated and L-lysine uptake into the mutant strains was analyzed. Among the
      thialysine-resistant strains a group of mutants was found, where the half
      saturation constant, KT, of the high-affinity transport system for lysine was
      higher than in the wild-type, the high-affinity transport system for basic amino
      acids being specifically affected. This was confirmed by a complementation test
      in which all the thialysine-resistant strains with a higher KT for lysine uptake
      belonged to one complementation group. Kinetic and genetic analysis showed that
      our mutants were identical with can1-1 mutants, showing that a single high
      affinity system for the transport of basic amino acids exists in S. pombe.

PMID- 1356080
TI  - [Evoked visual responses in schizophrenic patients].
AB  - The authors investigated during prolonged ambulatory treatment with the
      neuroleptic preparation isofloxythepine (IFT) changes of visually induced
      responses in 24 psychotic patients. The reference group was formed by 10 healthy
      volunteers examined before and after administration of a single dose of IFT by
      the oral route. In addition to the visually induced responses the authors
      investigated also plasma prolactin levels (PRL). It was found that the latency of
      the P1 peak and amplitude between peaks A1 are in psychotic patients altered, as
      compared with healthy subjects. The latency of the P1 peak is after a single dose
      of IFT in healthy subjects longer and the amplitude A1 higher than in the sick
      group. In healthy subjects after administration of IFT a negative correlation was
      observed between the amplitude and the basal PRL level. In patients no
      relationship was found between PRL levels and parameters of the visually induced
      response.

PMID- 1356081
TI  - Powder coating mixture of a novel anxiolytic, Y-23684: dissolution
      characteristics and bioavailability.
AB  - A powder coating mixture was investigated with a view toward improving the
      dissolution property of the anxiolytic 2-(4-chlorophenyl)-5,6-dihydro-[1]benzo
      thiepino-[5,4-c]-pyrida zin-3(2H)-one 7-oxide (1), which was barely water
      soluble. The powder coating mixture in various ratios of 1 and cornstarch was
      prepared in an automated mortar. Among these mixtures, at the optimum ratio of 1
      and cornstarch (2:1, 67% drug content), the powder coating mixture gave a
      maximized effect for solubilizing 1 on the bases of stability and solubility.
      Conventional granules were made from the 67% powder coating mixture. The granules
      showed an excellent absorption profile in beagle dogs. The mechanism of the
      solubilizing effect resulting from a pharmaceutical process was also discussed.

PMID- 1356083
TI  - International poster parade: sight bites from the 18th World Congress of
      Dermatology New York City June 12 to 18, 1992.
AB  - Most of what we learn comes from reading, not from listening. Thus, for us, the
      poster presentation is ideal. It allows us to escape from the confinement of the
      lecture hall and from the constraint of having to listen to the obvious, the
      repetitious, the uninteresting, and the irrelevant. Come with us and scan those
      posters that caught our roving clinical eye as we viewed a thousand poster
      "lectures."

PMID- 1356082
TI  - Partial release of aminopeptidase N from larval midgut cell membranes of the
      silkworm, Bombyx mori, by phosphatidylinositol-specific phospholipase C.
AB  - 1. The membrane anchor of aminopeptidase N associated with larval midgut cell
      membranes of the silkworm, Bombyx mori, was investigated by using
      phosphatidylinositol-specific phospholipase C (PIPLC) and proteases. 2.
      Aminopeptidase N, which was virtually all localized in the brush border membrane,
      was solubilized by PIPLC but not by papain or trypsin. 3. Detergent-solubilized
      amphiphilic aminopeptidase N was converted into a hydrophilic form by PIPLC but
      not by papain. 4. Either of these effects of PIPLC on aminopeptidase N was
      maximally 40%. 5. These results suggest that in larval midgut cells of the
      silkworm, B. mori, at least 40% aminopeptidase N is anchored in the brush border
      membrane via glycosyl-phosphatidylinositol.

PMID- 1356084
TI  - Comparison of strategies to detect and quantitate uniquely marked cells in intra-
      and inter-species hemopoietic chimeras.
AB  - Evaluation of the outcome of successful bone marrow transplantation and indepth
      studies of transplantation biology rely increasingly upon detection and
      enumeration of donor hemopoietic cells in the transplanted recipients. The
      ability to detect and enumerate low levels of donor engraftment in interphase
      cell subpopulations in hemopoietic chimeras is particularly important for studies
      of mixed lineage chimerism, early relapse manifestations, and engraftment of
      subpopulations present at low frequency. We describe and compare the sensitivity
      and specificity of DNA-based detection strategies (fluorescence in situ
      hybridization, in vitro DNA amplification using the polymerase chain reaction)
      and flow cytometric analysis of cell surface markers to detect cells carrying
      marker DNA or proteins in syngeneic (mouse-to-mouse) and xenogeneic (mouse-to
      human, monkey, sheep) backgrounds. DNA-based detection strategies offer
      advantages of rapid analysis and enumeration of target cell frequencies with
      detection sensitivities approximating 10(-4). The sensitivity of
      immunofluorescence-linked flow cytometric-based detection of nucleated leukocytes
      approached 10(-3), whereas flow cytometric-based detection of fixed human
      erythrocytes was feasible at cell frequencies of 10(-5). Data described in this
      manuscript should facilitate selection of appropriate methodologies for
      assessment of hemopoietic chimerism following transplantation.

PMID- 1356085
TI  - Clinical applications of cytometry: 6th annual meeting.
AB  - The Sixth Annual Clinical Applications of Cytometry Meeting was held September 11
      14, 1991, in Charleston, SC. Attendance reached a record 470. The meeting
      provides a forum for interactions among investigators who utilize cytometry as a
      tool in their clinical immunology, cell biology, hematology, and cancer
      investigations. Clinical laboratory directors and their technical staff find the
      meeting of practical value because of the presentation of new applications that
      they can take home to their own laboratories. The emphasis of the meeting is on
      advances in the application of cytometry to clinical problems. Often, advances
      result from new dyes or reagents or improved instrumentation. Sometimes they
      result from advances in biology that make the studies possible. Occasionally a
      new way of looking at the same data provides a useful answer. In every case, the
      effort is to provide a reliable, straightforward way to quantitate biologic
      information in order to provide improved diagnosis or treatment of human disease.

PMID- 1356086
TI  - [Hantavirus infection with acute kidney failure].
AB  - Hantavirus infection was confirmed by history, symptoms and biochemical changes,
      as well as immunofluorescence test in 29 patients (24 men, 5 women; mean age 36.9
      +/- 11.5 years) with nontraumatic renal failure (ANF), retrospectively in 15
      patients. Cardinal symptoms were acute onset (n = 29), fever (n = 27), pain in
      the flanks, abdomen or head (n = 27), reduced glomerular filtration rate (n =
      29), proteinuria (n = 25) and thrombocytopenia (n = 16). Normal renal function
      was restored in all patients. Follow-up examination of 15 patients 6-7 years
      after the acute illness revealed normal blood pressure, normal serum creatinine,
      absent proteinuria and normal inulin clearance in all, thus confirming the
      favourable prognosis of the infection in Western Europe. Nonetheless, because
      Hantavirus infection is by no means rare, it should be included in the
      differential diagnosis of acute renal failure.

PMID- 1356087
TI  - Effect of the cyclopyrrolones suriclone and RP 59037 on body temperature in mice.
AB  - The effects of the cyclopyrrolones suriclone and RP 59037 on body temperature
      were investigated in male TO mice. The full agonist suriclone (3, 10, 30 mg/kg
      i.p.) produced significant hypothermia which was inhibited by concurrent
      administration of benzodiazepine receptor antagonists of both benzodiazepine
      (flumazenil; 10 mg/kg i.p.) and beta-carboline (ZK 93426; 3 mg/kg i.p.)
      structure. The response to suriclone (10 mg/kg i.p.) was also attenuated by
      benzodiazepine (Ro 17-1812; 10 mg/kg i.p.) and beta-carboline (ZK 91296; 30 mg/kg
      i.p.) partial agonists - which have no effect on body temperature per se. In
      contrast with these compounds, the cyclopyrrolone partial agonist RP 59037 (10,
      30 mg/kg i.p.) produced significant hypothermia itself (although it was much less
      efficacious in this respect than the full agonist) and at a dose of 30 mg/kg
      failed to block the decrease in body temperature induced by suriclone (10 mg/kg
      i.p.). Thus suriclone acts as a full agonist at benzodiazepine receptors in the
      body temperature paradigm. RP 59037 possesses some partial agonist properties in
      this model, however, it appears to have greater intrinsic activity than other
      partial agonists tested previously.

PMID- 1356088
TI  - Tolerance to hypoactivity and sensitization to hyperactivity after chronic
      treatment with a presynaptic dose of lisuride in rats.
AB  - We studied the adaptive changes of the locomotor effects of lisuride, a selective
      agonist for dopamine (DA) D2 receptors, and the functional state of D1 and D2
      receptors after repeated administration of lisuride at a dose supposed to act
      preferentially on DA autoreceptors. Rats were treated daily with saline or
      lisuride, at a dose that causes a significant reduction in locomotor activity
      when given to naive rats (25 micrograms/kg i.p.), for 33 days and the effect of
      different challenging doses of the drug on locomotor activity was measured at
      different times during and after the treatment. The functional state of D1 and D2
      DA receptors was evaluated by measuring SKF 82526-stimulated and LY 171555
      inhibited adenylate cyclase (AC) activity in the caudatus/putamen, nucleus
      accumbens and substantia nigra and naive and chronically treated rats. There was
      a progressive decline in the ability of lisuride to decrease locomotor activity
      in rats given daily injections of lisuride, and there was a marked reduction in
      the threshold dose of lisuride for causing hypermotility. The functional state of
      DA receptors, positively or negatively linked to AC activity, was not modified by
      the treatment. The most suitable explanation of the reported adaptive behavioral
      changes is a down-regulation of DA autoreceptors after chronic treatment with
      presynaptic doses of lisuride.

PMID- 1356089
TI  - Chaperoning practices of Ohio family physicians.
AB  - BACKGROUND: The medical literature contains no consistent recommendations
      regarding chaperon practices during physical examination of patients. The
      objective of this study was to determine the chaperon practices of Ohio family
      physicians. METHODS: A questionnaire was mailed to all 1,786 active members of
      the Ohio Academy of Family Physicians. The questionnaire solicited information
      about the physicians' chaperon practices during physical examinations of the
      rectum, sexual and genital organs, and the female chest. RESULTS: The response
      rate was 74.6%. During female genital examinations, chaperons were used by 79.4%
      of male and 31.9% of female family physicians. Only 1.4% of male and 14.4% of
      female physicians used chaperons during male genital examinations. Chaperon
      practices were influenced by the gender of the physician and patient, the type of
      examination, and the availability of an assistant. CONCLUSIONS: No standard of
      care exists regarding chaperon practices among Ohio family physicians.

PMID- 1356090
TI  - [Rectal ganglioneuromatosis and multiple type IIb endocrine neoplasia].
AB  - Intestinal tract ganglioneuromatosis was discovered in a 27-year old man through
      surgical biopsy specimens obtained after acute intestinal obstruction. The
      patient then developed type IIb endocrine neoplasia including a marfanoid
      morphotype, mucosal neuromatosis, metastatic medullary carcinoma of the thyroid
      and bilateral pheochromocytoma. The histological and clinical features, the
      pathophysiological mechanisms of intestinal ganglioneuromatosis and its place
      within the intricate group of neurocristopathies are discussed.

PMID- 1356092
TI  - Biochemical and serological characterization of Escherichia coli fimbrial antigen
      F165(2).
AB  - Mannose-resistant hemagglutinating fimbrial antigen F165 is produced by
      Escherichia coli strains associated with septicemia in piglets and calves. A
      fimbrial component with an M(r) of 17,200 as determined by SDS-PAGE was purified
      to homogeneity from F165-positive E. coli strain 4787 of serogroup O115. This
      fimbrial component of F165 antigen was named F165(2). Separation procedures
      included fast protein liquid chromatography with a Superose 12 column followed by
      ultracentrifugation and 0.15 M ethanolamine buffer (pH 10.5) dissociation. Upon
      removal of ethanolamine, the fimbrial component reassociated into fimbriae. Amino
      acid composition analysis indicated that the fimbrial component molecule
      comprised 158 amino acid residues of which 37.3% were hydrophobic. The amino acid
      composition and the isoelectric point (9.5) were readily distinguishable from
      those of F1 fimbriae. The amino acid sequence was determined for approximately
      40% of the molecule. For the first 33 residues, the F165(2) sequence was
      identical to that of F1B fimbriae and very similar to that of F1C. Fimbriae
      F165(2) could nevertheless be differentiated antigenically from F1C fimbriae as
      demonstrated by the immunodot technique using cross-absorbed antisera.

PMID- 1356091
TI  - The effect of dopamine on rat gastric motility.
AB  - The inhibitory mechanism of dopamine (DA) on rat gastric motility was
      investigated in association with DA receptors. Gastric movement was assessed
      according to the method of Jacoby et al and was expressed with the system of
      Ludwick et al. (1968). DA inhibited gastric movement in both the corpus and
      antrum in a dose-dependent manner. Domperidone, a specific antagonist of DA2
      receptor, suppressed DA-induced inhibition of gastric movement in a dose
      dependent manner. SCH23390, a specific antagonist of DA1 receptor did not affect
      DA-induced inhibition of gastric movement. LY171555, a specific agonist of DA2
      receptor, inhibited gastric movement in both the corpus and antrum in a dose
      dependent manner. SKF38393, a specific agonist of DA1 receptor, did not affect
      gastric movement. These results indicate that DA plays an important role in the
      inhibitory regulation of gastric motility, through DA2 receptor but not DA1
      receptor.

PMID- 1356093
TI  - Recent amplification of triose phosphate isomerase related sequences in lettuce.
AB  - A random cDNA clone was identified as distinguishing near-isogenic lines for
      downy mildew resistance in lettuce. The clone detected multiple restriction
      fragments in genomic Southern blots of lettuce. Restriction fragment length
      polymorphisms (RFLPs) detected by this clone mapped to separate clusters of
      resistance genes; therefore, these sequences were studied in a greater detail.
      Sequence analysis indicated that the cDNA encoded the glycolytic enzyme triose
      phosphate isomerase (TPI). The lettuce clone shares 85% sequence similarity at
      the amino acid level with TPI from maize. TPI-related sequences were mapped in
      lettuce using three crosses. Ten loci were distributed in six linkage groups.
      Possible mechanisms of amplification and dispersion were investigated.
      Retrotransposition was excluded, since intron five is retained in all TPI-related
      genomic sequences. Large scale chromosomal rearrangements were not involved, as
      RFLP markers flanking TPI loci were not duplicated. A high level of genomic
      variability was detected by the TPI clone; 37 different restriction fragments
      were detected in Southern hybridizations to 64 populations of lettuce including
      47 cultivars of Lactuca sativa and five wild species. Species distantly related
      to L. sativa had few TPI loci, indicating that their amplification and dispersion
      were recent and had occurred after the emergence of the L. serriola complex.

PMID- 1356094
TI  - Thymopentin reduces the susceptibility of aged mice to cutaneous leishmaniasis by
      modulating CD4 T-cell subsets.
AB  - BALB/c mice are highly susceptible to Leishmania major infection. The
      susceptibility increases progressively with the age of the mice. Aged mice
      produce progressively lower levels of interleukin-2 (IL-2) and interferon-gamma
      (IFN-gamma) but higher levels of IL-4 compared to younger mice. Thymopentin, a
      pentapeptide with thymopoietin activity, dramatically increases the resistance to
      Leishmania major infection in aged mice. The thymopentin-treated mice produce
      enhanced levels of IL-2 and IFN-gamma, but significantly reduced amounts of IL-4.
      Thus, it appears that the age-related susceptibility to cutaneous leishmaniasis
      is correlated with the enhancement of Th2 and the reduction of Th1 cell
      activities. Furthermore, thymic hormone may play an important role in the
      induction and function of these two subsets of CD4 T cells.

PMID- 1356095
TI  - The functional activity of Fc gamma RII and Fc gamma RIII on subsets of human
      lymphocytes.
AB  - Subsets of human lymphocytes were isolated from peripheral blood using magnetic
      beads coated with anti-CD4, -CD8, -CD19 or -CD56 antibodies to yield T4, T8, B
      and natural killer (NK) cell suspensions with greater than 95% purity. The
      functional activity of Fc gamma receptor II (Fc gamma RII) and Fc gamma receptor
      III (Fc gamma RIII) on these subsets was assessed by measuring rosette formation
      with red cells sensitized with known levels of either rabbit IgG or human
      (monoclonal or polyclonal) IgG1 anti-D, IgG3 anti-D or IgG3 anti-c (E-IgG). Lysis
      of red cells by K cells (mediated by Fc gamma RIII) in antibody-dependent cell
      mediated cytotoxicity (ADCC) assays was promoted by polyclonal and some
      monoclonal antibodies. Using these 'ADCC+' antibodies, minimum red cell
      sensitization levels required to promote rosette formation with NK cells were
      2000 IgG1 or IgG3 molecules/red cell compared to 15,000 IgG1 or 4000 IgG3
      molecules/red cell with 'ADCC-' monoclonal antibodies. The greater efficiency of
      ADCC+ antibodies is consistent with their previously reported ability to bind Fc
      gamma RIII via CH2 and CH3 domains whereas ADCC- antibodies bind only via CH3
      domains. B cells formed rosettes only at high levels of sensitization:
      approximately 60,000 IgG1 or 20,000 IgG3 anti-D molecules/cell. These data
      reflect the low affinity of Fc gamma RII for monomeric human IgG. Although over
      90% of NK cells bound anti-CD16, and 70% formed rosettes with red cells
      sensitized with rabbit IgG (30,000 molecules/cell), only 25% of NK cells formed
      rosettes with E-IgG3 at 100,000 IgG molecules/cell. Approximately 35% of B cells,
      10% of T8 cells but no T4 cells formed rosettes with E-IgG (100,000 IgG3
      molecules/cell). With T8, B and NK cells, IgG3 anti-D promoted greater rosette
      formation than IgG1 anti-D at comparable levels of sensitization. Presumably the
      longer hinge region of IgG3 enabled it to bridge the gap between negatively
      charged lymphocytes and red cells more efficiently than IgG1.

PMID- 1356096
TI  - Inhibition of T-cell mediated cytotoxicity by Novobiocin suggests multiple
      pathways for both CD4+ and CD8+ cytotoxic T cells.
AB  - The effect of the topoisomerase II inhibitor Novobiocin on T-cell mediated
      cytotoxicity was tested under various assay conditions. When effector cells were
      class I major histocompatibility complex (MHC)-specific CD8+ cytotoxic T cells
      (Tc), Novobiocin caused a biphasic pattern of inhibition and the two components
      of the inhibition could be separated based on Ca2+ requirement. Unseparated
      populations of class II MHC specific Tc, containing CD4+ and CD8+ effectors gave
      the same pattern of inhibition. When CD8+ cells were depleted from the latter
      population of effectors, different patterns of inhibition from those obtained
      with CD8+ Tc were seen and furthermore the target affected the pattern of
      inhibition. Overall the results add further support to there being more than one
      pathway of CD8+ T-cell mediated cytotoxicity and further illustrate differences
      between CD4+ and CD8+ T-cell mediated cytotoxicity.

PMID- 1356097
TI  - Marked dendritic cell-T cell cluster formation in the pancreatic lymph node of
      the non-obese diabetic mouse.
AB  - Dendritic cells (DC) isolated from various lymph node (LN) groups of pre-diabetic
      non-obese diabetic (NOD) (4-20 weeks of age) and age-sex-matched control mice
      were analysed for their surface antigen phenotype and their ability to cluster
      lymphocytes. The draining LN of the pancreas (PLN) of 8-week-old NOD mice with
      active autoimmune disease were significantly enlarged in comparison to the
      axillary LN of the same NOD mice and the PLN from control mice. NOD DC isolated
      from PLN and other LN demonstrated classical DC morphology, were highly major
      histocompatibility complex (MHC) class II antigen positive, and were 50-70% 33D1+
      (DC-specific antibody). In an assay for DC-T cell clustering, DC from the PLN of
      8-20-week-old NOD formed large clusters (greater than 10 cells) with PLN cells at
      a frequency three to 20 times greater than that observed with DC and LN cells
      from the PLN of 8-week-old control mice, the PLN of 4-week-old NOD mice, and
      axillary/inguinal LN of 8-week-old NOD mice. Clustered cells were 80% Thy-1.2+
      (56% L3T4, 17% Lyt-2+). Specificity of clustering was demonstrated as PLN DC
      clustered only PLN T cells in the assay; axillary/inguinal (A/I) DC added to PLN
      LC did not induce clustering nor did PLN DC induce clustering of the A/I
      population. Cell proliferation in isolated PLN DC/LC clusters was markedly
      greater than that of A/I clusters and of non-clustered PLN cells. These data
      demonstrate that DC from the PLN of NOD mice with active autoimmune disease form
      stable clusters with T cells from the PLN and these clusters are the major source
      of proliferating T cells in these LN. We hypothesize that PLN DC may play an
      important role in the autoimmune disease of the NOD mouse.

PMID- 1356098
TI  - Ancestral haplotypes reveal the role of the central MHC in the immunogenetics of
      IDDM.
AB  - The major histocompatibility complex (MHC) contains multiple and diverse genes
      which may be relevant to the induction and regulation of autoimmune responses in
      insulin dependent diabetes mellitus (IDDM). In addition to HLA class I and II,
      the possible candidates include TNF, C4, and several other poorly defined
      polymorphic genes in the central MHC region. This study describes two approaches
      which take advantage of the fact that the relevant genes are carried by highly
      conserved ancestral haplotypes such as 8.1 (HLA-B8, TNFS, C4AQ0, C4B1, DR3, DQ2).
      First, three "diabetogenic" haplotypes (two Caucasoid and one Mongoloid) have
      been compared and it has been shown that all three share a rare allele of BAT3 as
      well as sharing DR3, DQ2. In 43 sequential patients with IDDM the cross product
      ratio for BAT3S was 4.8 (p less than 0.01) and 6.9 for HLA-B8 plus BAT3S (p less
      than 0.001). Second, partial or recombinant ancestral haplotypes with either HLA
      class I (HLA-B8) or II (HLA-DR3, DQ2) alleles were identified. Third, using
      haplotypic polymorphisms such as the one in BAT3, we have shown that all the
      patients carrying recombinants of the 8.1 ancestral haplotype share the central
      region adjacent to HLA-B. These findings suggest that both HLA and non-HLA genes
      are involved in conferring susceptibility to IDDM, and that the region between
      HLA-B and BAT3 contains some of the relevant genes. By contrast, similar
      approaches suggest that protective genes map to the HLA class II region.

PMID- 1356099
TI  - Polymorphic analysis of the three MHC-linked HSP70 genes.
AB  - Three genes encoding members of the M(r) 70,000 heat shock protein family (HSP70)
      are known to lie in the class III region of the human major histocompatibility
      complex. In order to determine whether these genes or their protein products
      exhibit any polymorphism the three genes have been specifically amplified from
      genomic DNA and sequenced. The HSP70-1 and HSP70-2 genes encode the major heat
      inducible HSP70. A comparison of the nucleotide sequences of these genes from B8,
      SC01, DR3, B18, F1C30, DR3, and B7, SC30, DR2 haplotypes has revealed only very
      limited sequence variation which is not associated with any amino acid
      polymorphism. The HSP70-Hom gene encodes a protein that is highly related to
      HSP70-1, but which is not heat-inducible. Nucleotide sequence analysis of this
      gene from different haplotypes has revealed a Met----Thr amino acid substitution
      at residue 493 in a number of the haplotypes tested. This variable amino acid
      lies in the proposed peptide-binding site of the HSP70-Hom protein.

PMID- 1356100
TI  - Involvement of both HLA and Ig heavy chain haplotypes in human IgA deficiency.
AB  - Immunoglobulin-A deficiency (IgA-D) is the most common human Ig class deficiency
      with an estimated frequency of approximately 1 in 500 in the Swedish population.
      We investigated the immunoglobulin heavy chain constant region gene segments
      (IGHC) in 103 individuals with IgA-D and the immunoglobulin heavy chain variable
      region gene segments (IGHV) in 20 of these, in order to identify a possible
      molecular basis of the defect. No deletions of IGHV gene segments of the VH2,
      VH5, and VH6 families or the IGHG genes were observed. In the IGHC, there were,
      however, differences in the restriction fragment length polymorphism frequencies
      of IGHG genes where the Bam HI haplotype "H2" [IGHGP, 10 kilobases (kb), IGHG2,
      25 kb; and IGHG4, 9.0 kb] was overrepresented. The mean serum levels of IgG4 and
      IgE were significantly lower in individuals (both IgA-D subjects and healthy
      controls) homozygous for the H2 haplotype than in individuals homozygous for the
      H1 haplotype (IGHGP, 8.8 kb, IGHG2, 13.5 kb, and IGHG4, 9.4 kb). IgA-D subjects
      homozygous for HLA DQB1*0201 (DQw2), a marker that has previously been reported
      to show a strong association with IgA deficiency, showed a similar reduction of
      serum levels of IgG4 and IgE as compared with DQB1*0201 negative IgA-D subjects.
      These findings suggest that the two loci found to be associated with IgA
      deficiency may act via a common pathway.

PMID- 1356101
TI  - Pharmacokinetics of two oral liquid formulations of oxatomide in children.
AB  - A study on the pharmacokinetics of two suspensions of oxatomide at the
      concentrations of 25 and 2.5 mg/ml was carried out on 12 children (7M, 5F) with a
      mean age of 9 years and weight of 29 kg. The plasmatic concentration peak, the
      time to reach the peak and the area under the curve displayed no significant
      differences between the two formulations. The maximum concentrations and the peak
      time of oxatomide in children are similar to those observed in adults.

PMID- 1356102
TI  - Gastric, intestinal and colonic absorption of a series of beta-blockers in the
      rat.
AB  - Gastric, intestinal and colonic absorption rates of a series of eleven beta
      blockers (alprenolol hydrochloride, atenolol, bunolol hydrochloride, penbutolol
      sulphate, pronethalol hydrochloride, metoprolol, oxprenolol, bevantolol,
      bufuralol, propranolol hydrochloride and timolol maleate) were estimated using
      Doluisio's method. The gastric absorption rate was very low and the absorption
      rate constant could not be assessed accurately in all cases. In the small
      intestine, the absorption rate constants, Ka, at pH 6.2 ranged between 0.38 h-1
      for atenolol and 4.28 h-1 for penbutolol. In the colon, the rate of drug
      absorption at pH 7.5 ranged between 0.12 h-1 for atenolol and 2.15 h-1 for
      penbutolol. In most cases, colonic absorption rate constants were of the same
      order as those obtained in the small intestine, demonstrating the good
      penetrability through colonic membrane of the series studied. The relationship
      between absorption rate constants found in the small intestine and colon and the
      partition constant ([1/Rf]-1), was studied for this non-homologous series of beta
      blocker drugs. In both cases, the functional hyperbolic absorption model proposed
      by Wagner and Sedman [1973] was the most representative.

PMID- 1356103
TI  - Antiglucocorticoid action of dehydroepiandrosterone in young obese Zucker rats.
AB  - Dehydroepiandrosterone (DHEA) reduces weight gain in the hypercorticosteronemic
      Zucker fatty rat, an animal model of genetic obesity. However, the mechanism of
      action of DHEA is still unclear. We propose that DHEA acts as an
      antiglucocorticoid in the Zucker fatty rat. To test this hypothesis we examined
      DHEA's ability to block the activation of the glucocorticoid-inducible enzymes
      tyrosine aminotransferase (TAT) and ornithine decarboxylase (ODC) by
      dexamethasone (i.p. 5 micrograms/100 g body weight) in hepatic tissue of 6-10
      week old Zucker rats. Injections of DMSO, the vehicle, served as a control. DHEA
      alone did not affect TAT, but when DHEA (500 micrograms/100 g b.w.) was
      administered simultaneously with dexamethasone, activation did not occur. Similar
      results were seen using a second tissue (kidney). We conclude that DHEA can act
      acutely as an antiglucocorticoid in the young obese Zucker rat and hypothesize
      that its chronic anti-obesity effect may reflect, at least in part, a chronic
      antiglucocorticoid activity.

PMID- 1356104
TI  - Pupillometry in clinical psychophysiological diagnostics: methodology and
      proposals for application in psychiatry.
AB  - The change in pupillary reactions may be considered as an important parameter of
      the autonomic nervous system. By means of pupillometry, it became possible to
      measure both objectively and economically these reactions. The method of
      microprocessor-assisted "static" and light evoked "dynamic" pupillometry is
      demonstrated. A high reliability for the static variable of pupillometry was also
      evaluated. Variables measured during "static and dynamic" pupillometry were
      factor-analyzed. Four factors (static, dynamic, stimulus specific and restitution
      dependent) were obtained regardless of whether investigations were carried out in
      normals or in psychiatric patients. Examples of utilization of pupillometry in
      psychopharmacology and mental disorders are also described in this essay.

PMID- 1356105
TI  - [Surgery of chronic pancreatitis].
AB  - Surgery for chronic pancreatitis may be indicated for local complications, or if
      the differential diagnosis between cancer and pancreatitis is uncertain, or if
      pain does not respond to conservative treatment. Local complications of chronic
      pancreatitis are the most frequent indications for operation. Pseudocysts are
      often associated with other local complications, and a high mortality rate is
      observed when haemorrhage occurs. Duodenopancreatectomy can be performed with low
      mortality, and is indicated if malignancy cannot be excluded, or in the patient
      with medically intractable pain in whom a pancreatico-jejunostomy is technically
      not feasible.

PMID- 1356106
TI  - Cellular and enzymatic activities of a synthetic heteropolymer double-stranded
      RNA of defined size.
AB  - We have synthesized a novel heteropolymer double-stranded RNA (dsRNA) molecule of
      defined length and strandedness (dsRNA309) and evaluated its ability to induce
      cytokine gene expression, activate dsRNA-dependent enzymes, and inhibit both
      tumor cell growth and virus replication. Unlike the conventionally studied
      synthetic homopolymer dsRNAs, polyinosinic acid:polycytidylic acid (poly(I-C))
      and its mismatched analogue polyinosinic:polycytidylic, uridylic acid (poly(I
      C12,U), dsRNA309 possessed restricted biological activity. dsRNA309 was unable to
      inhibit tumor cell growth or efficiently induce cytokine (i.e. interferon-beta
      and interleukin-1 alpha) gene expression. However, dsRNA309 was able to inhibit
      virus replication and activate dsRNA-dependent intracellular enzymes, 2'-5'
      oligoadenylate synthetase (2'-5' A synthetase) and the dsRNA-activated inhibitor
      kinase in in vitro assay systems. Overall, dsRNA309 provided a means for
      examining the mechanisms governing the dsRNA-regulated antiviral and
      antiproliferative responses, and studies with dsRNA309 demonstrated that the
      ability of a synthetic dsRNA to activate dsRNA-dependent intracellular enzymes
      does not necessarily predict the same gene inducing capacity.

PMID- 1356107
TI  - Molecular cloning and chromosomal localization of a human gene encoding D-amino
      acid oxidase.
AB  - Genomic clones covering the entire sequence of the gene encoding human D-amino
      acid oxidase (DAO) (EC 1.4.3.3), one of the principal and characteristic
      flavoenzymes of peroxisomes, were isolated from human placental genomic libraries
      with the aid of a previously cloned cDNA for human DAO as a probe. Nucleotide
      sequence analysis revealed that the gene, present as a single copy in the human
      genome, comprises 11 exons and spans 20 kilobase pairs. The protein sequences
      containing the catalytically important residues, Tyr-228 and His-307, are coded
      for by separate exons. Heterologous transcription initiation sites were
      identified by primer extension analysis, and the sequence of the 5'-flanking
      region of the DAO gene was found to show some features common to other mammalian
      genes, such as those of glucocorticoid and the cAMP-responsive element. An
      additional noteworthy feature is the presence of promoter-like sequences in the
      first intron of the gene. In addition, two sequences of alternating pyrimidine
      and purine nucleotides, (CA)20 and (CA)17, are also present in the first intron.
      Such sequences may play some role in the expression of the DAO gene in human
      tissues. With the use of genomic DNAs prepared from human and Chinese hamster
      somatic hybrid cells as templates for the polymerase chain reaction, the gene for
      DAO was localized to human chromosome 12.

PMID- 1356108
TI  - Multiple DNA elements responsible for transcriptional regulation of the ornithine
      decarboxylase gene by protein kinase A.
AB  - Transcription of the ornithine decarboxylase (ODC) gene is rapidly elevated by
      activation of protein kinase A (PKA). The additive influence of three cis-acting
      elements is responsible for this regulation in an adrenal carcinoma cell line.
      Two sites, CRE2 at -48 base pairs (bp) relative to the start of transcription and
      CRE3 at +95 bp, are identical to the core motif of the cAMP-responsive element
      (CRE) of the somatostatin gene and are conserved in the mouse, rat, and human ODC
      genes. Mutation of CRE2 resulted in a substantial decrease in basal promoter
      activity, as well as a 5-fold decrease in inducibility of the ODC promoter by
      PKA. CRE3 did not contribute to the basal activity of the ODC promoter, but
      mutation of this site resulted in a 2-fold decrease in inducibility by PKA.
      Deletion of a 45-bp sequence (GC-box) located 5' of CRE2, also resulted in a 2
      fold decrease in inducibility of the ODC promoter. DNase I protection revealed
      the presence of protein binding at CRE2, the TATA box, and the GC-box of the ODC
      promoter. Mutation of CRE2 resulted in loss of protection of this sequence, as
      well as the 3' extension of the footprint over the TATA box, without affecting
      interactions at the GC box. Antibodies to the well characterized CRE-binding
      protein CREB recognized proteins binding to CRE2, suggesting that binding of
      CREB, or an antigenically related protein, is important for the activity of CRE2.
      Additionally, recombinant CREB bound to a DNA probe containing the CRE2 sequence.

PMID- 1356109
TI  - Abdominal aortic dissection due to idiopathic medial aortopathy in a 32-year-old
      Caucasian man.
AB  - A case of dissection of the abdominal aorta in a 32-year-old Caucasian man
      associated with a histological diagnosis of granulomatous aortitis and a clinical
      diagnosis of idiopathic medial aortopathy is described. The relationship between
      giant cell "temporal" arteritis, Takayasu's disease and idiopathic medial
      aortopathy is discussed.

PMID- 1356110
TI  - From Vineberg to bypass: a "second-hand" internal mammary artery.
AB  - A patient operated upon 20 years ago for myocardial revascularization with two
      Vineberg procedures and one coronary artery bypass graft (CABG) on the right
      coronary artery had a recurrence of unstable angina due to the thrombosis of the
      left internal mammary artery (IMA) and the right CABG. The right IMA was patent
      but stenosed distally. Reoperation was performed with a direct end to side
      anastomosis of the patent right IMA onto the left anterior descending artery and
      a saphenous vein graft as a CABG on the marginal branch. We comment on the choice
      of this "second hand" IMA graft and the pathological appearances of the patent
      IMA.

PMID- 1356113
TI  - Current status of research on the Xp21 myopathies.

PMID- 1356112
TI  - Co-expression of insulin and somatostatin genes in pancreatic endocrine cells
      selected for their high level of insulin gene transcription.
AB  - RW cells are pancreatic endocrine RIN cells that have been stably transfected
      with a chimeric gene that places the expression of the dominant selection gpt
      gene under the control of the insulin gene regulatory sequences. These RW cells
      were examined for hormone content using immunocytochemistry. This analysis shows
      that: first, there are cells that are negative for insulin although they were
      cultured under selective pressure. Second, there is a higher proportion of
      somatostatin-producing cells than in the parental RIN cells; these somatostatin
      cells form two populations: one of cells containing only somatostatin and,
      surprisingly, one made of cells containing both insulin and somatostatin. Thus:
      (1) expression of the transfected and endogenous insulin regulatory sequences is
      not regulated in a coordinate fashion; (2) the presence of both hormones in the
      same cell suggests that the regulation of the expression of insulin and
      somatostatin genes and the differentiation pathway of the two respective cell
      types may be closely related.

PMID- 1356111
TI  - Isolation of peroxisome assembly mutants from Saccharomyces cerevisiae with
      different morphologies using a novel positive selection procedure.
AB  - We have developed a positive selection system for the isolation of Saccharomyces
      cerevisiae mutants with disturbed peroxisomal functions. The selection is based
      on the lethality of hydrogen peroxide (H2O2) that is produced in wild type cells
      during the peroxisomal beta-oxidation of fatty acids. In total, 17 mutants having
      a general impairment of peroxisome biogenesis were isolated, as revealed by their
      inability to grow on oleic acid as the sole carbon source and their aberrant cell
      fractionation pattern of peroxisomal enzymes. The mutants were shown to have
      monogenetic defects and to fall into 12 complementation groups. Representative
      members of each complementation group were morphologically examined by
      immunocytochemistry using EM. In one mutant the induction and morphology of
      peroxisomes is normal but import of thiolase is abrogated, while in another the
      morphology differs from the wild type: stacked peroxisomal membranes are present
      that are able to import thiolase but not catalase. These mutants suggest the
      existence of multiple components involved in peroxisomal protein import. Some
      mutants show the phenotype characteristic of glucose-repressed cells, an
      indication for the interruption of a signal transduction pathway resulting in
      organelle proliferation. In the remaining mutants morphologically detectable
      peroxisomes are absent: this phenotype is also known from fibroblasts of patients
      suffering from Zellweger syndrome, a disorder resulting from impairment of
      peroxisomes.

PMID- 1356114
TI  - Incidence of tardive dyskinesia in affective disorder patients.

PMID- 1356115
TI  - Combined use of beta-adrenergic blocking agents and long-term cardiac pacing for
      patients with the long QT syndrome.
AB  - OBJECTIVE: The objective of this study was to review our current experience using
      a combination of beta-adrenergic blocking agents and long-term cardiac pacing to
      treat patients with the idiopathic long QT syndrome. BACKGROUND: Patients with
      the idiopathic long QT syndrome are at high risk for sudden cardiac death. Before
      combination therapy, 20 of the 21 study patients experienced either cardiac
      arrest (n = 8) or syncope (n = 18) and 11 had documented polymorphous ventricular
      tachycardia. Nine of these patients had not responded to isolated beta-blocker
      therapy and five had not responded to isolated left cervicothoracic
      sympathectomy. METHOD: All patients were treated with combined beta-blocker
      therapy and long-term cardiac pacing at a rate designed to normalize the QT
      interval. RESULTS: Cardiac pacing at rates of 70 to 125 beats/min resulted in
      shortening of the QT and corrected QT (QTc) intervals from 517 +/- 78 and 541 +/-
      62 ms to 404 +/- 37 and 479 +/- 41 ms, respectively. The mean follow-up interval
      after institution of pacing was 55 +/- 45 months. The only sudden death occurred
      in a patient who had discontinued beta-blocker therapy. Syncope occurred in four
      patients, two of whom had interrupted pacemaker function due to lead fracture.
      Pacemaker problems, partly attributable to the specific rate required for QT
      interval shortening and to avoidance of T wave sensing, were relatively common.
      No patient who continued the combination therapy died, but 10% of these patients
      had a recurrence of symptoms. CONCLUSIONS: Combination therapy with a beta
      blocker and cardiac pacing appears to be a highly effective primary therapy for
      symptomatic patients with the long QT syndrome and to provide excellent
      adjunctive therapy for patients who require insertion of an automatic internal
      defibrillator.

PMID- 1356116
TI  - Preserved ventricular pump function after a marked reduction of left ventricular
      mass.
AB  - OBJECTIVES: This study was designed to evaluate the long-term effects of
      combination therapy with an angiotensin-converting enzyme inhibitor and a beta
      adrenergic blocking agent on the relation between the decrease in arterial
      pressure at rest and during exercise and the decrease in left ventricular mass.
      BACKGROUND: A variety of antihypertensive drugs including angiotensin-converting
      enzyme inhibitors and beta-blockers have been shown to reduce ventricular
      hypertrophy, although little is known about combination therapy and the time
      course of such a reduction. METHODS: Twenty-one patients with previously
      untreated essential hypertension were treated with a low dose combination of 50
      mg of atenolol and 10 mg of enalapril once daily for 39 months. Cardiovascular
      findings were assessed by two-dimensionally guided M-mode echocardiography in the
      pretreatment phase and after 6 and 39 months of combination therapy. RESULTS:
      Combination therapy reduced arterial pressure at rest from 161/108 to 130/86 mm
      Hg (p less than 0.001) and exercise arterial pressure at 100 W from 192/112 to
      167/95 mm Hg (p less than 0.001). After 6 months of treatment, significant
      decreases in interventricular septal thickness (9%, p less than 0.001), posterior
      wall thickness (9%, p less than 0.001) and left ventricular mass index (16%, p
      less than 0.001) were demonstrated on the echocardiogram. After 39 months of
      therapy, reductions in these values were 28% (p less than 0.001), 29% (p less
      than 0.001) and 40% (p less than 0.001), respectively. CONCLUSIONS: Long-term
      treatment with combination therapy of atenolol and enalapril produced significant
      reductions in arterial pressure at rest and during exercise accompanied by a
      marked reduction of left ventricular mass. However, whereas arterial pressure
      decreased immediately and remained unchanged, left ventricular mass decreased
      more gradually and continued to decrease throughout the treatment period of
      greater than 3 years. Despite this marked reduction in left ventricular mass,
      left ventricular pump function was well preserved during rest and exercise.

PMID- 1356118
TI  - Mechanisms, diagnosis, and treatment of sinusitis in children and adults.
      Symposium proceedings. Scottsdale, Arizona, January 24-25, 1992.

PMID- 1356117
TI  - Effects of budesonide and bambuterol on circadian variation of airway
      responsiveness and nocturnal symptoms of asthma.
AB  - Effects of the inhaled corticosteroid budesonide and the oral beta-agonist
      bambuterol on the nocturnal worsening of asthma were studied in patients with
      allergic asthma with a circadian peak expiratory flow variation greater than or
      equal to 15% (group 1, n = 8) and less than 15% (group 2, n = 9). Airflow
      limitation and airway responsiveness to histamine were measured during 24 hours
      after 4 weeks of treatment with (A) 0.4 mg budesonide at 8 AM and 8 PM, (B) 20 mg
      bambuterol at 8 PM, and (C) placebo, in a randomized, crossover design. Patients
      in group 1 had worse nocturnal symptom scores and a greater airway responsiveness
      than patients in group 2; in addition, patients in group 1 had a larger increase
      in responsiveness during the night (1.1 versus 0.6 doubling concentrations [DC]).
      Both budesonide and bambuterol improved responsiveness more at night than during
      daytime, thus decreasing circadian variation: at 4 AM, increases in PC20 were 2.0
      DC after budesonide and 0.8 DC after bambuterol, compared with placebo.
      Bambuterol reduced circadian variation in FEV1, but in contrast to budesonide,
      did not improve 24-hour mean levels of FEV1 and PC20. Both drugs beneficially
      influenced nocturnal symptoms; the effects of budesonide were stronger than those
      of bambuterol. Our findings demonstrate that budesonide and bambuterol reduce
      nocturnal airway responsiveness and asthma symptoms and suggest a relationship
      between the degree of airway responsiveness and the presence of nocturnal
      symptoms of asthma.

PMID- 1356119
TI  - Synaptic transmission in rat cardiac neurones.
AB  - Intracellular recordings of spontaneous synaptic activity and synaptic responses
      to fibre tract stimulation were taken from neurones of ganglia isolated from the
      left atrium and interatrial septum of the rat. In six out of 57 neurones studied,
      spontaneous fast excitatory postsynaptic potentials (EPSPs) were recorded. Single
      stimulation of fibre tracts approaching the ganglion resulted in an all-or-none
      response consisting of an EPSP, from which an action potential abruptly appeared.
      This response disappeared in Ca(2+)-free/high-Mg2+ solution, indicating that it
      was orthodromic in origin. EPSPs were markedly exaggerated and prolonged by
      neostigmine (1-5 microM). EPSPs produced by high-frequency (0.1-20 Hz) fibre
      tract stimulation were markedly attenuated when compared with responses to single
      fibre tract stimulation, although they usually remained suprathreshold for spike
      initiation. High concentrations of hexamethonium (1 mM) and d-tubocurarine (300
      microM) failed to inhibit responses to single fibre tract stimulation, although
      they completely abolished responses to high-frequency stimulation. Responses to
      single fibre tract stimulation were abolished by trimetaphan (greater than or
      equal to 100 microM). No slow synaptic responses were detected during single or
      high-frequency fibre tract stimulation. All cardiac neurones that responded
      orthodromically were highly excitable: they had a short post-spike after
      hyperpolarization (AHP) and responded with multiple firing to prolonged membrane
      depolarization. It is concluded that cardiac neurones, in the region of the heart
      studied here, receive single 'strong' cholinergic inputs from some fibre tracts
      approaching the ganglion that elicit EPSPs accompanied by spikes. EPSPs are
      rather resistant to ganglion-blocking agents and subject to frequency modulation.

PMID- 1356120
TI  - Effects of consecutive administration of central and peripheral anticholinergic
      agents on respiratory sinus arrhythmia in normal subjects.
AB  - Respiratory sinus arrhythmia is thought to be vagally mediated, since it
      disappears after atropine, but the site of action of the drug (central vs.
      peripheral) accounting for this effect has not been elucidated. To investigate
      the effects of anticholinergic agents on respiratory arrhythmia, ten healthy
      subjects received an intravenous bolus of tropatepine (a presumed central
      antagonist) at a dose of 0.08 mg per kg of body weight, then, 7 min later,
      prifinium (a peripheral antagonist) at a dose of 0.1 mg per kg of body weight.
      Respiratory sinus arrhythmia during controlled breathing was evaluated as the
      area under the high-frequency peak of the heart rate variability spectrum
      coinciding with the respiratory frequency +/- 0.02 Hz. The power of this high
      frequency peak decreased by 55% after tropatepine (P less than 0.05) with a
      concomitant increase of the mean RR interval from 930 to 1072 ms (P less than
      0.01). When prifinium was added, a further but non-significant decrease of
      respiratory arrhythmia was observed, while the mean RR interval decreased from
      1072 to 714 ms (P less than 0.01). The low-frequency components (0.05 to 0.15 Hz)
      of the power spectrum, significantly decreased (P less than 0.05) after infusion
      of both drugs. In conclusion, tropatepine depresses respiratory sinus arrhythmia
      with a paradoxical concomitant bradycardia. This suggests that tropatepine acts
      like a pure central muscarinic antagonist, in support of the hypothesis that a
      central cholinergic receptor is involved in the respiratory modulation of heart
      rate.

PMID- 1356121
TI  - Amino acid gradients across the intestinal circulation in fetal lambs.
AB  - Amino acids, including glutamine, glutamate and asparagine are major metabolic
      substrates for the adult enterocyte of several species. To determine whether
      circulating amino acids are utilized by the fetal intestine, we studied nine
      fetal sheep (mean gestational age 128 +/- 5 days; term: 147 days). Catheters were
      inserted into the descending aorta (DA) and the mesenteric vein (MV) to allow for
      simultaneous blood sampling across the intestine. Fetal blood gas, haemoglobin;
      O2 saturation and O2 tension were measured. Ammonia was determined by an
      enzymatic method and HPLC analysis was used to measure the content of all amino
      acids in DA (descending aorta) and MV (mesenteric vein). Intestinal blood flow
      measurements were obtained using the radionuclide microsphere method. Intestinal
      blood flow (81 +/- 28 ml/min/100g) and arterial pH (7.37 +/- 0.04) were within
      normal range for unstressed fetal lambs. Glutamine and glutamate were the only
      amino acids that were significantly taken up across the fetal intestinal
      circulation. The fetal intestine extracted approximately 21% of the delivered
      glutamine (6.8 +/- 4.5 mumol/min/100g), 7% of the delivered glutamate (1.3 +/-
      1.1 mumol/min/100g) and 2.7% of the delivered oxygen (43.0 +/- 19.1
      mumol/min/100g). These data suggest that glutamine and glutamate are major
      substrates for the intestine in unstressed fetal lambs.

PMID- 1356122
TI  - Localization of immunoreactive tyrosine hydroxylase in the goldfish retina with
      pre-embedding immunolabeling with one-nanometer colloidal gold particles and gold
      toning.
AB  - The goal of this study was to develop an alternative to silver intensification
      for visualizing small colloidal gold particles by light and electron microscopy.
      The isolated goldfish retina was labeled with rabbit antiserum to tyrosine
      hydroxylase and 1-nm colloidal gold-conjugated goat anti-rabbit IgG. The gold
      particles were enlarged by toning with gold chloride, followed by reduction in
      oxalic acid. Dopaminergic interplexiform cells were clearly visible by light
      microscopy and, in lightly-fixed material treated with detergent, they were
      labeled in their entirety. Labeling was qualitatively similar, although less
      extensive, in material fixed and processed for electron microscopy. The labeled
      processes were apparent in ultra-thin sections viewed at low magnification, but
      the gold-toned particles were not so large that they obscured subcellular
      structures. The procedure apparently had no deleterious effects on the tissue,
      since the ultrastructural preservation was comparable to that seen with other pre
      embedding immunolabeling methods. The technique was simple, reliable and, since
      the gold solutions were so dilute, relatively inexpensive.

PMID- 1356123
TI  - Prolonged IL-2 receptor alpha/CD25 expression after T cell activation via the
      adhesion molecules CD2 and CD28. Demonstration of combined transcriptional and
      post-transcriptional regulation.
AB  - The T cell adhesion molecule CD28 provides a costimulatory signal in combination
      with CD2 and CD3 mAb. CD28 regulates the expression of cytokines by T cells, not
      only IL-2, but also IL-1 alpha and CSF-1, usually synthesized by accessory cells.
      We have investigated the mechanisms through which CD28 modulates the expression
      of the IL-2R alpha chain. Whereas activation through CD2 or CD28 alone induced no
      or only low IL-2R alpha chain expression, activation through CD2 plus CD28 led to
      both a high and prolonged (greater than 14 days) cell surface and mRNA
      expression. In contrast, immobilized CD3 mAb-dependent activation induced a
      transient expression of the IL-2R alpha chain, which was neither further
      increased nor prolonged by CD28 costimulation. Upon CD2 plus CD28 stimulation,
      the half-lives of the two IL-2R alpha transcripts increased progressively between
      days 1 and 4, in contrast to each pathway alone. Whereas each activation pathway
      alone induced either no (CD2) or low (CD28) levels of IL-2R alpha gene
      transcription, the CD2 plus CD28 stimulation was associated with its increased
      transcription, which persisted at similar rates between 5 and 96 h post
      stimulation. The in vitro costimulation via the CD2 and CD28 molecules thus
      regulates the expression of the IL-2R alpha gene both at the transcriptional and
      post transcriptional levels. Our results therefore demonstrate a new
      immunoregulatory function of the CD28 molecule on IL-2R alpha expression, which,
      through its increased transcription rate and stabilization, could, together with
      high levels of cytokines secretion, be responsible for the prolonged T cell
      proliferation.

PMID- 1356124
TI  - Regulation of LFA-1 avidity in human B cells. Requirements for dephosphorylation
      events for high avidity ICAM-1 binding.
AB  - Regulation of the avidity of LFA-1 (CD11a/CD18, alpha L beta 2) for its ligand
      ICAM-1 (CD54) was studied in human B cells by evaluating the effects of a phorbol
      ester, anti-IgM antibodies, staurosporine, and okadaic acid. We monitored changes
      in LFA-1 avidity by quantifying binding of cells to an immobilized rICAM-1 fusion
      protein. In this assay, the protein kinase C-activating phorbol ester PDB and
      anti-IgM antibodies, as well as the protein kinase inhibitor, staurosporine, were
      able to induce LFA-1-dependent binding to ICAM-1. This demonstrates that the high
      avidity state of LFA-1 can be induced by a protein kinase C-dependent and by a
      protein kinase C-independent pathway. Furthermore, treatment of the cells with
      the protein phosphatase inhibitor, okadaic acid, inhibited binding to ICAM-1.
      Treatment with staurosporine before addition of okadaic acid not only induced
      enhanced binding of cells to ICAM-1, but also dramatically reduced the ability of
      okadaic acid to inhibit binding. These results suggest a critical role for a
      protein phosphatase in inducing the high avidity state of LFA-1 as well as a role
      for a protein kinase in inducing the low avidity state of LFA-1.

PMID- 1356125
TI  - IL-10 is produced by subsets of human CD4+ T cell clones and peripheral blood T
      cells.
AB  - Murine IL-10 has been reported originally to be produced by the Th2 subset of
      CD4+ T cell clones. In this study, we demonstrate that human IL-10 is produced by
      Th0, Th1-, and Th2-like CD4+ T cell clones after both Ag-specific and polyclonal
      activation. In purified peripheral blood T cells, low, but significant, levels of
      IL-10 were found to be produced by the CD4+CD45RA+ population, whereas CD4+CD45RA
      "memory" cells secreted 5- to 20-fold higher levels of IL-10. In addition, IL-10
      was produced by activated CD8+ peripheral blood T cells. Optimal induction of IL
      10 was observed after activation by specific Ag and by the combination of anti
      CD3 mAb and the phorbol ester tetradecanoyl phorbol acetate, whereas the
      combination of calcium ionophore A23187 and 12-O-tetradecanoylphorbol-13-acetate
      acetate was a poor inducer of IL-10 production. Kinetic studies indicated that IL
      10 was produced relatively late as compared with other cytokines. Maximal IL-10
      mRNA expression in CD4+ T cell clones and purified peripheral blood T cells was
      obtained after 24 h, whereas maximal IL-10 protein synthesis occurred between 24
      h and 48 h after activation. No differences were observed in the kinetics of IL
      10 production among Th0, Th1-, and Th2-like subsets of CD4+ T cell clones. The
      results indicate a regulatory role for IL-10 in later phases of the immune
      response.

PMID- 1356126
TI  - Taxol increases steady-state levels of lipopolysaccharide-inducible genes and
      protein-tyrosine phosphorylation in murine macrophages.
AB  - Taxol, a microtubule stabilizing agent, exhibits promise in the treatment of
      breast and ovarian tumors. Recently, this novel drug has been shown to activate
      murine macrophages to express TNF-alpha and to down-regulate TNF-alpha receptors,
      activities shared by bacterial LPS. Our study sought to determine if taxol could
      regulate gene expression in murine macrophages and to examine further the ability
      of taxol to generate an LPS-like signal. Toward this end, the ability of taxol to
      induce TNF-alpha mRNA and five other genes (IL-1 beta, IP-10, D3, D7, and D8)
      associated with LPS-activation of macrophages was examined by Northern blot
      analysis. Taxol alone (1-30 microM) induced murine C3H/OuJ macrophages to secrete
      bioactive TNF-alpha and express increased levels of each of the six genes under
      investigation. The magnitude and the kinetics of induction of each gene closely
      resembled that seen with Escherichia coli K235 LPS. Macrophages from LPS
      hyporesponsive C3H/HeJ mice, however, failed to induce detectably any of the
      genes in response to taxol, despite being sensitive to the microtubule
      stabilizing effects of taxol as determined by immunofluorescence microscopy. The
      gene induction activity of taxol was in marked contrast to an alternative
      macrophage activator, heat killed Staphylococcus aureus, which induced a distinct
      gene profile in C3H/OuJ macrophages and which was equally active in C3H/OuJ and
      C3H/HeJ macrophages. These data are consistent with an ability of taxol to
      generate an LPS-like signal, possibly through a common signaling intermediate. As
      a first step toward identifying signal responses shared by taxol and LPS, we have
      shown that taxol, as shown previously for LPS, rapidly induces the tyrosine
      phosphorylation of a 41- and 42-kDa protein.

PMID- 1356127
TI  - Conservation of the HLA-DQB2 locus in nonhuman primates.

PMID- 1356128
TI  - Detection of human immunodeficiency virus type 2 in brain tissue.
AB  - Infection due to human immunodeficiency virus (HIV) type 2 is believed to cause a
      clinical picture similar to that of HIV-1, although extensive data are not
      available. In 2 patients with West African exposure and neurologic symptoms, HIV
      2 was detected in the central nervous system using DNA and RNA polymerase chain
      reaction, in situ hybridization, and immunohistology. In the first patient, the
      neurologic disease was most likely due to productive infection with HIV-2. In the
      second, a combination of neuropathologic abnormalities (including the presence of
      HIV-2) explained the clinical features. Thus HIV-2, like HIV-1, can be readily
      detected in brain tissue in patients with neurologic abnormalities, although the
      exact role of HIV-2 in pathogenesis of AIDS-associated neurologic disease
      requires further study.

PMID- 1356129
TI  - Intramolecular transformation reaction of the glutathione thiyl radical into a
      non-sulphur-centred radical: a pulse-radiolysis and EPR study.
AB  - The thiyl radical derived from glutathione (GSH) is shown to decay rapidly in
      aqueous solution by intramolecular rearrangement reactions into the non-sulphur
      centred radical 1. The reaction is induced by OH- with a rate constant of 5 x
      10(9) dm3 mol-1 and is also observable at near-neutral conditions (at
      physiological pH values around 7.5 the rate of formation of 1 amounts to
      approximately 1 x 10(3) s-1). The activation enthalpy and entropy at pH 8.4 and
      20 degrees C were found to be 26.7 kJ mol-1 and -77 J mol-1 K-1, respectively.
      Radical 1 was unequivocally identified by EPR as the alpha-amino radical at the
      glutamyl residue of GSH. It is relatively long-lived with typical bimolecular
      decay rate constants of the order of (2-20) x 10(6) dm3 mol-1 s-1. At higher GSH
      concentrations the formation of 1 is retarded but not inhibited. All radicals,
      sulphur- as well as non-sulphur-centred ones are connected via equilibria, partly
      under the action of 'repair' processes of GSH. These repair processes, however,
      are slow (k much less than 1.4 x 10(5) dm3 mol-1 s-1). The equilibria are
      established quite rapidly and were found to be far on the side of the non-sulphur
      centred radical under all conditions employed. Radical 1 possesses reducing
      properties as evidenced by its fast reaction with 4-nitro-acetophenone (PNAP) to
      yield PNAP.- (k = 7 x 10(8) dm3 mol-1 s-1).

PMID- 1356130
TI  - Heavy ion-induced DNA double-strand breaks in yeast.
AB  - DNA double-strand break (dsb) induction in diploid yeast was measured by neutral
      sucrose sedimentation after exposure to very heavy ions with values of linear
      energy transfer (LET) ranging from about 300 to 11500 ke V/microns. Linear
      fluence dependencies were found in all cases from which dsb production cross
      sections (sigma dsb) could be calculated. Corresponding cross-sections for cell
      killing (sigma i) were derived from final slopes of survival curves measured in
      parallel and for the same fluence range. A close correlation was found between
      sigma i and sigma dsb. It is calculated that over the entire LET range, including
      30 MeV electron irradiation, about 22 dsb are induced per lethal event when high
      exposures are considered.

PMID- 1356131
TI  - The role of non-protein sulphydryls in determining the chemical repair rates of
      free radical precursors of DNA damage and cell killing in Chinese hamster V79
      cells.
AB  - Chinese hamster V79 fibroblasts were irradiated in the gas explosion apparatus
      and the chemical repair rates of the oxygen-dependent free radical precursors of
      DNA double-strand breaks (dsb) and lethal lesions measured using filter elution
      (pH 9.6) and a clonogenic assay. Depletion of cellular GSH levels, from 4.16
      fmol/cell to 0.05 fmol/cell, by treatment with buthionine sulphoximine (50 mumol
      dm-3; 18 h), led to sensitization as regards DNA dsb induction and cell killing.
      This was evident at all time settings but was particularly pronounced when the
      oxygen shot was given 1 ms after the irradiation pulse. A detailed analysis of
      the chemical repair kinetics showed that depletion of GSH led to a reduction in
      the first-order rate constant for dsb precursors from 385 s-1 to 144 s-1, and for
      lethal lesion precursors from 533 s-1 to 165 s-1. This is generally consistent
      with the role of GSH in the repair-fixation model of radiation damage at the
      critical DNA lesions. However, the reduction in chemical repair rate was not
      proportional to the severe thiol depletion (down to approximately 1% for GSH) and
      a residual repair capacity remained (approximately 30%). This was found not to be
      due to compartmentalization of residual GSH in the nucleus, as the repair rate
      for dsb precursors in isolated nuclei, washed virtually free of GSH, was
      identical to that found in GSH-depleted cells (144 s-1), also the OER remained
      substantially above unity. This suggests that other reducing agents may have a
      role to play in the chemical repair of oxygen-dependent damage. One possible
      candidate is the significant level of protein sulphydryls present in isolated
      nuclei.

PMID- 1356132
TI  - The influence of ras oncogene expression on radiation response in the Rat-1 cell.
AB  - We evaluated the effect of H-ras oncogene expression on resistance to ionizing
      radiation in cultured rat fibroblasts. The Rat-1 cell line, and two Rat-1
      derivatives, MR4 and MR7, carrying a ZN-regulatable metallothionein-rasT24 fusion
      gene were used to study the effects of the ras oncogene on radiation sensitivity.
      Cells were irradiated with a 137Cs source (450 cGY/min) in the presence or
      absence of ZnSO4. Multiple cell survival studies did not show an appreciable
      difference in sensitivity to radiation among the lines in the presence or absence
      of ras oncogene expression.

PMID- 1356133
TI  - Single-cell gel electrophoresis applied to the analysis of UV-C damage and its
      repair in human cells.
AB  - DNA breaks in eukaryotic cells can be detected by alkaline electrophoresis of
      cells embedded in agarose. DNA containing breaks extends in the direction of the
      anode forming an image resembling the tail of a comet. We have adapted this
      procedure of single cell gel electrophoresis (SCGE) for studying DNA damage and
      repair induced by UV-C-radiation, using HeLa cells. UV-C itself does not induce
      DNA breakage, and though cellular repair of UV-C damage produces DNA breaks as
      intermediates, these are too short-lived to be detected by SCGE. Incubation of UV
      C-irradiated cells with the DNA synthesis inhibitor aphidicolin causes
      accumulation of incomplete repair sites to a level readily detected by SCGE even
      after doses as low as 0.5 J m-2 and incubation for as little as 5 min. We have
      also used SCGE to study UV-C-dependent incision, repair synthesis and ligation in
      permeable cells. Finally, we have incubated permeable cells, after UV-C
      irradiation, with exogenous UV endonuclease, examining the consequent breaks both
      by SCGE and by alkaline unwinding in order to express results of the
      electrophoretic method in terms of DNA break frequencies. The sensitivity of the
      SCGE technique can thus be estimated; as few as 0.1 DNA breaks per 10(9) daltons
      are detected.

PMID- 1356134
TI  - Synergism between electrolysis and methylene blue photodynamic action in
      Escherichia coli.
AB  - There is interest in the use of photodynamic therapy for the treatment of certain
      diseases, including cancer. However, weak penetration of visible light in tissues
      has restricted its use. In this study the possibility of enhancing photodynamic
      effects by the use of energies that penetrate more deeply in tissues was
      investigated. Weak electric currents (1.0 mA) applied to Escherichia coli cells
      for short periods, producing little or no lethal damage, was found to act
      synergistically with the photodynamic action of methylene blue, significantly
      enhancing the effects of this treatment. This synergism exists also between
      electrolysis and X-rays but not between electrolysis and UV-254 nm. It is
      suggested that this synergism might eventually be used to improve the results
      obtained in therapeutic practice based on the utilization of photodynamic action.

PMID- 1356135
TI  - EPR study of mouse tissues in search for adaptive responses to low level whole
      body X-irradiation.
AB  - Effect of a low dose of whole-body X-irradiation (D1 = 0.075 Gy) of mice on some
      biochemical changes induced in the spleen and thymus by a subsequent challenge
      dose (D2 = 1.5 Gy) was studied by electron paramagnetic resonance (EPR). Kunming
      and SHK mice were used. Concentration of ribonucleotide reductase (RR) in the
      spleen and thymus of unirradiated Kunming mice was 0.70 and 0.46 microM
      respectively, and of unirradiated SKH mice--0.37 and 0.21 microM respectively
      (systematic error 45%). For mice exposed only to the low dose (D1 group), a
      stimulating effect on RR activity in spleen and thymus was found, while in mice
      subjected only to the D2 dose (D2 group) activity of the enzyme in the organs
      decreased considerably 18 h after irradiation. The group of mice irradiated with
      D1 and D2 doses, given at a 6-h interval (D1 plus D2 group), showed a RR activity
      in the organs lower than D1 and higher than D2 groups. This finding indicates
      that there exists an adaptation-like response to a low-dose whole-body
      irradiation in murine spleen and thymus. This low 'inductive' dose makes the
      organs' RR less susceptible to inhibition induced by a subsequent challenge dose.
      Preliminary results showed that the same kind of response is probably a
      characteristic of the RR content of splenocytes as well as of the rate of
      thymidine incorporation into splenocytes. 5-Thyml radicals of DNA (TH radicals)
      induced in whole tissues by gamma-irradiation in vitro at 77 K were also studied.
      Radiochemical yield of these radicals (4.0 and 5.3 nmol j-1), for spleen and
      thymus respectively of unirradiated Kunming mice, and 2.3 and 2.6 nmol J-1, for
      spleen and thymus respectively of unirradiated SHK mice (systematic error 30%),
      decreased significantly in both organs upon D2 irradiation. This decrease,
      however, was the consequence of DNA content diminishing upon D2 irradiation
      rather than change of DNA radiosensitivity: the beta value of TH radicals, i.e.
      yield of radicals per unit mass of DNA in each organ was equal for the mice from
      all D1, D1 plus D2, D2 and control groups. The beta values of TH radicals in
      mouse spleen and thymus were of the same order of magnitude compared with the
      yield of the single-strand breaks of DNA measured previously in rat organs just
      after whole-body irradiation, i.e. about 1 x 10(2) (Gy x 10(12) Da)-1.

PMID- 1356136
TI  - Cellular recovery kinetics for postirradiation treatments.
AB  - Postirradiation cellular recovery kinetics for delayed plating, araA, hypertonic
      saline (HS) treatments and their combinations, were analysed in the framework of
      the previously developed dsb model (Ostashevsky 1989). Two possible types of DNA
      double-strand break (dsb) repair kinetics were considered: cooperative, where the
      rate-limiting step is related to a DNA molecule, and non-cooperative, where the
      rate-limiting step is related to a dsb. The following estimates were made for
      plateau-phase V79 cells: (1) HS induces a temporary block of dsb repair. The
      estimates for the dsb repair block duration are about 0.6 h for a 10-min
      treatment and about 1.2 h for a 20-min treatment. (2) HS creates additional DNA
      fragments. The number of these fragments calculated for 0.37 M NaCl treatment, in
      a way independent of the type of dsb repair, was consistent with the number
      estimated for 0.5 M NaCl treatment for cooperative dsb repair, but not for
      noncooperative dsb repair. (3) The estimated time constant for the process
      restricting the formation of DNA fragments was 10-20 min. In the presence of 200
      400 microM araA, the rate of this process should decrease 2-5-fold. (4) The time
      constant for the araA recovery kinetics coincides with that for dsb repair, in
      agreement with experimental data. (5) For delayed plating recovery the kinetics
      curve calculated for cooperative dsb repair fits well experimental data, in
      contrast to the curve calculated for non-cooperative dsb repair.

PMID- 1356137
TI  - Induction of thermotolerance by chemical agents in enucleate erythrocytes.
AB  - Erythrocytes treated with various chemical agents for 1 h at 37 degrees C showed
      resistance to a subsequent 1 h heat treatment at 53 degrees C. Maximal
      thermotolerance was observed 6 h after 3 mM DNP and 0.03 mM disulfiram treatment
      and 4 h after diamide exposure at 0.3 mM. Our results suggest that chemically
      induced thermotolerance to heat treatment in erythrocytes was similar to heat
      induced thermotolerance.

PMID- 1356139
TI  - Differentiation of mosquito-pathogenic strains of Bacillus sphaericus from non
      toxic varieties by ribosomal RNA gene restriction patterns.
AB  - DNA from 17 strains of Bacillus sphaericus, including representatives of all the
      established DNA homology groups, was cleaved with EcoRI or HindIII and fragments
      were separated by agarose gel electrophoresis. Southern blots of this DNA were
      hybridized to a radioactively labelled DNA probe prepared from the cloned 16S
      rrnB ribosomal RNA operon of Escherichia coli. Banding patterns of the
      chromosomal DNA digests and the autoradiograms were specific to DNA homology
      groups I (B. sphaericus sensu stricto), IIA (mosquito-pathogenic strains), IIB
      (B. fusiformis) and V, but groups III and IV were not clearly distinguished. This
      suggests that the mosquito-pathogenic strains represent a separate subspecies.

PMID- 1356138
TI  - Molecular cloning and sequencing of the upstream region of the major Bacillus
      subtilis autolysin gene: a modifier protein exhibiting sequence homology to the
      major autolysin and the spoIID product.
AB  - The upstream region of the N-acetylmuramoyl-L-alanine amidase gene (cwlB; a major
      Bacillus subtilis autolysin) was cloned into Escherichia coli by chromosome
      walking. Sequencing of the region showed the presence of two open reading frames,
      one (designated as cwbA) which starts at a UUG codon and encodes a polypeptide of
      705 amino acids with an M(r) of 76,725, and the other (designated as lppX),
      upstream of cwbA, comprising 102 amino acids and having a signal sequence
      characteristic of a lipoprotein. Purification of the CwbA protein and
      determination of its N-terminal amino acid sequence revealed that it contains a
      presumed signal peptide which is processed after Ala at position 25 from the N
      terminal, and that the M(r) of the mature form is 75,000. The amino acid
      sequences of the N-terminal and C-terminal regions of CwbA were found to be
      highly homologous with those of the cell wall binding domain of CwlB and the
      spoIID gene product, respectively. CwbA stimulated the major autolysin activity
      approximately threefold in vitro. These data indicate that CwbA is the modifier
      protein of the major autolysin reported by Herbold, D. R. & Glaser, L. (1975;
      Journal of Biological Chemistry 250, 1676-1682). In-frame fusion between the lppX
      and lacZ genes demonstrated that lppX is translated in vivo and expressed during
      the exponential growth phase.

PMID- 1356140
TI  - Clonal variation of chromosome size derived from the rDNA cluster region in
      Candida albicans.
AB  - Of the eight Candida albicans chromosomes, chromosome 2, assigned by the MGL1
      probe, is more variable in size than the other chromosomes among strains. We
      found that the clonal variation of chromosome 2, which carries a rDNA gene,
      occurred at a frequency of up to 10% of the progeny clones. After total
      chromosomal digestion with XhoI, which has no recognition sites within the rDNA
      repeat unit, the fragments containing the rDNA cluster were detected by Southern
      hybridization. The difference in fragment sizes corresponded to the clonal size
      variation of chromosome 2. The intensity of hybridization with rDNA also
      correlated with the difference in size. In addition, there was no size change in
      the non-rDNA region as detected by NotI digestion of chromosome 2, and there was
      no observed change in the individual rDNA basic repeat unit size. From these
      lines of evidence, we confirmed that the clonal size variation of chromosome 2
      which occurs at high frequency is derived from the size change of the rDNA
      cluster.

PMID- 1356141
TI  - Purification and some properties of glutamate dehydrogenase and glutamine
      synthetase from Paracoccus denitrificans.
AB  - The purification and some properties of NADP-dependent glutamate dehydrogenase
      (GDH) and glutamine synthetase (GS) from the facultatively anaerobic Gram
      negative bacterium Paracoccus denitrificans were investigated. The enzymes were
      purified to homogeneity using a procedure which involved affinity chromatography
      on Blue Sepharose CL-6B as the major purification step. The recoveries in the
      purification of GDH and GS were 28% and 64%, respectively. The specific activity
      of purified GDH was 183 nkat (mg protein)-1 (deaminating reaction). GDH was
      composed of subunits of molecular mass 47 kDa and the native enzyme was either a
      tetramer or hexamer. The apparent Km values for L-glutamate, NADP, 2
      oxoglutarate, NADPH and ammonia were 1.5 mM, 5.9 microM, 0.47 microM, 12.5 microM
      and 14 mM, respectively. The specific activity of purified GS was 1125 nkat (mg
      protein)-1 (transferase reaction). The molecular mass of native GS was 570 kDa;
      it was composed of 12 subunits of molecular mass 50.1 kDa. The apparent Km values
      for L-glutamine and hydroxylamine in the transferase reaction were 2.1 and 2.4
      mM, respectively; those of ammonia, L-glutamate and ATP in the biosynthetic
      reaction were 0.03, 1 and 0.17 mM, respectively. After the adenylylation of GS,
      the Km for L-glutamine and L-glutamate increased and reached the values of 8.0
      and 27 mM, respectively. The effects of the changes in GS activity on the ammonia
      metabolism of Paracoccus denitrificans are discussed.

PMID- 1356142
TI  - NE/DA interactions in prefrontal cortex and their possible roles as
      neuromodulators in schizophrenia.
AB  - The monoaminergic innervation of the rat prefrontal cortex arises from well
      defined mesencephalic nuclei, with noradrenergic (NE) neurons located in the
      locus coeruleus, dopaminergic (DA) neurons located in the ventral tegmental area,
      and serotonergic (5-HT) neurons originating in the raphe nuclei. Specific
      destruction of the NE bundle was found to induce morphological (i.e., sprouting)
      as well as metabolic (i.e., changes in rate of DA utilization) modifications of
      mesocortical DA neurons, suggesting that these two catecholaminergic systems have
      functional interactions within the prefrontal cortex. This was substantiated by
      experiments showing that DA afferents modulate the sensitivity of cortical post
      synaptic beta-adrenergic receptors and that, reciprocally, NE neurons control the
      sensitivity of cortical D1 receptors. Behavioural and pharmacological data have
      further indicated that the stimulation of cortical alpha-1 adrenergic receptors
      inhibits cortical DA transmission at D1 receptors. Secondly, we have attempted to
      analyze how such interactions between neuromodulatory systems may be related to
      the development of mental diseases such as schizophrenia. On the basis of studies
      in the literature describing the effects produced by the ingestion of
      hallucinogenic drugs or data collected regarding REM sleep, it is postulated that
      two modes of brain functioning exist: analogical and cognitive. Each mode is
      characterized by differences in the relative activities of NE, DA and 5-HT
      neurons. At birth, during REM sleep, and following the ingestion of
      hallucinogens, the mode of brain functioning is essentially analogical; in
      contrast, both analogic and cognitive modes are postulated to coexist in the
      awake state. Oscillations between these two modes are under the control of
      monoaminergic systems on which an increase in cortical DA release favours the
      cognitive processing mode, whereas intermittent activations of NE neurons would
      switch the brain into the analogical mode of processing. It is proposed that
      schizophrenic patients with "positive" symptoms suffer from an abnormal
      preponderance of the analogical mode while awake, whereas "negative" symptoms are
      due to the excessive presence of the cognitive mode. Although pure biological
      deficits cannot be excluded, these dysfunctions could be related to the absence
      of particular environmental variables early in the development of these patients.
      This condition is probably required to establish normal regulatory control of
      monoaminergic neuronal activity.

PMID- 1356143
TI  - The depolarization block hypothesis of neuroleptic action: implications for the
      etiology and treatment of schizophrenia.
AB  - Antipsychotic drugs are known to block dopamine receptors soon after their
      administration, resulting in an increase in dopamine neuron firing and dopamine
      turnover. Nonetheless, antipsychotic drugs must be administered repeatedly to
      schizophrenics before therapeutic benefits are produced. Recordings from dopamine
      neurons in rats have revealed that chronic antipsychotic drug treatment results
      in the time-dependent inactivation of dopamine neuron firing via over-excitation,
      or depolarization block. Furthermore, the clinical profile of the response to
      antipsychotic drugs appears to correspond to the dopamine system affected:
      antipsychotic drugs that exert therapeutic actions in schizophrenics inactivate
      dopamine neuron firing in the limbic-related ventral tegmental area, whereas
      drugs that precipitate extrapyramidal side effects cause depolarization block of
      the motor-related substantia nigra dopamine cells. One factor that remains
      unresolved with regard to the actions of antipsychotic drugs is the relationship
      between dopamine turnover and depolarization block--i.e., why does a significant
      level of dopamine release or turnover remain after antipsychotic drug treatment
      if dopamine cells are no longer firing? We addressed this question using an acute
      model of neuroleptic-induced depolarization block. In this model, dopamine cells
      recorded in rats one month after partial dopamine lesions could be driven into
      depolarization block by the acute administration of moderate doses of
      haloperidol. However, similar doses of haloperidol, which were effective at
      increasing dopamine levels in the striatum of intact rats, failed to change
      dopamine levels in lesioned rats. This is consistent with a model in which
      neuroleptic drugs exert their therapeutic effects in schizophrenics by causing
      depolarization block in DA cells, thereby preventing further activation of
      dopamine neuron firing in response to external stimuli. Thus, attenuating the
      responsivity of the dopamine system to stimuli may be more relevant to the
      therapeutic actions of antipsychotic drugs than receptor blockade or decreases in
      absolute levels of dopamine, which could presumably be circumvented by
      homeostatic adaptations in this highly plastic system.

PMID- 1356144
TI  - Localization of adenylyl and guanylyl cyclase in rat brain by in situ
      hybridization: comparison with calmodulin mRNA distribution.
AB  - Cyclic nucleotides are major intracellular mediators in the signal transduction
      events in synaptic neurotransmission of the CNS. Intracellular Ca2+ is known to
      regulate adenylyl cyclase (AC) in a calmodulin (CaM)-dependent manner, and
      guanylyl cyclase (GC), in an indirect manner through CaM-sensitive nitric oxide
      synthase. To ascertain the physiological significance of cyclic nucleotide second
      messenger systems, we have localized the mRNAs encoding AC, GC, and CaM in the
      rat brain by in situ hybridization using 35S-labeled RNA probes. The AC mRNA is
      widely distributed throughout the brain; strong hybridization signal was observed
      in the granular layers of the cerebellum, in the pyramidal and granule cells of
      the hippocampus, and in the olfactory system. These AC mRNA localizations are
      compatible with the distribution of Ca2+/CaM-sensitive AC activities. In contrast
      to AC mRNA distribution, GC mRNA has a more limited distribution. Significant
      signals were observed in the striatum, in the pyramidal and granule cells of the
      hippocampus, in the olfactory system, in the inferior and superior colliculus, in
      the Purkinje cells of the cerebellum, in the locus coeruleus, and in many
      pyramidal cells in the layers II-III and V of the cerebral cortex, and mainly, in
      the occipital cortex. In some discrete brain regions, a close correlation was
      found between enzyme activity and mRNA hybridization signal of GC. The distinct
      distribution of AC and GC mRNAs suggests that different cyclic nucleotide second
      messenger systems have specialized functions. On the other hand, CaM mRNA was
      colocalized with the AC and GC mRNA, but its distribution was more abundant and
      specific for neuronal cells, since there was little hybridization signal with CaM
      probe in neuronal fiber regions such as the corpus callosum and the anterior
      commissure. The high expression of CaM mRNA in neuronal cells is in agreement
      with its biochemical role in the regulation of various enzymes. Results of the
      present study should help in analyzing the role of cyclic nucleotides and CaM in
      physiological and pathological situations in the CNS.

PMID- 1356145
TI  - A novel N18TG2 x mesencephalon cell hybrid expresses properties that suggest a
      dopaminergic cell line of substantia nigra origin.
AB  - A dopaminergic neuroblastoma was derived using somatic cell fusion of rat
      embryonic mesencephalon cells and the murine neuroblastoma-glioma cell line
      N18TG2. The resulting interspecies hybrid, named MES23.5, has retained a stable
      phenotype and karyotype for a continuous culture period of 1 year. The hybrid
      exhibits several properties that suggest that the parent primary neurons
      originated in the substantia nigra. The cell line contains tyrosine hydroxylase,
      which is identifiable both by biochemical and immunological methods and
      synthesizes dopamine, but no other catecholamine. Additionally, the cell line
      expresses apparent voltage-gated CA2+ channels as measured by high-affinity omega
      conotoxin binding. The MES23.5 omega-conotoxin receptors are of similar affinity
      class to those found in adult rat mesencephalon. No dihydropyridine receptors, as
      measured by PN200-100 ligand binding, are present. None of these properties are
      found in the N18TG2 parent. At least three neuronal features, namely, tyrosine
      hydroxylase, dopamine synthesis, and omega-conotoxin receptor expression, are
      quantitatively elevated after sustained treatment with cAMP analogs. The cell
      line expresses a complex range of neural properties found in the dopaminergic
      neurons of the substantia nigra, and may therefore be useful elucidating further
      details of their cell biology.

PMID- 1356146
TI  - Anatomy and physiology of multipolar cells in the rat inferior collicular cortex
      using the in vitro brain slice technique.
AB  - Coronal brain slices from 21-50-d-old hooded rats were used to characterize
      intracellular responses of cells in both the external and dorsal cortices of the
      inferior colliculus (IC). These cells could generate both sodium and calcium
      spikes. Depending on current amplitude, depolarizing current pulses could elicit
      either phasic or tonic firing patterns, with spike frequency adaptation. Spiking
      also occurred at the offset of a hyperpolarizing pulse. These patterns were due
      primarily to the activation of calcium conductances. Stimulation of the
      commissural pathway connecting the left and right IC produced a short-latency
      monosynaptic IPSP followed by an EPSP(s) and a late polysynaptic IPSP(s). Non
      NMDA glutamate antagonists eliminated or reduced the amplitude of the EPSP and
      the late portion of the inhibition, while both IPSPs were blocked by GABAA
      antagonists. As described previously in guinea pig (Smith, 1986) and rat (Pierson
      et al., 1989), a large NMDA-mediated depolarizing event (paroxysmal depolarizing
      shift, or PDS) could be elicited by shocking the commissure of the IC in the
      presence of picrotoxin or bicuculline, NMDA, 4-aminopyridine, or in 0 Mg2+
      Ringer's. The picrotoxin-induced PDS was significantly reduced or abolished in
      Ringer's containing aminophosphonovalerate. Cells displaying the responses
      described were labeled with neurobiotin. Those labeled are medium-sized
      multipolar cells. Their dendrites are usually spiny and can extend superficially
      up to the cortical surface. Their thin axons give rise to collaterals that branch
      profusely within the cortex. The main axons project laterally along the
      circumference of the IC or medially into the commissure separating the collicular
      hemispheres.

PMID- 1356147
TI  - Hyperbaric oxygen therapy: contraindications and complications.
AB  - The literature is replete with references regarding the use of hyperbaric oxygen
      (HBO) therapy to treat various human maladies. However, the oral and
      maxillofacial surgery literature is lacking in information regarding patient
      selection criteria and possible contraindications to HBO therapy, as well as
      possible risks and/or complications of such therapy. This article details patient
      selection criteria, discusses relative and absolute contraindications to HBO
      therapy, and describes the potential risks and complications of this therapy.

PMID- 1356148
TI  - Cathepsin B/L-, elastase-, tryptase-, trypsin- and dipeptidyl peptidase IV-like
      activities in gingival crevicular fluid: a comparison of levels before and after
      periodontal surgery in chronic periodontitis patients.
AB  - Gingival crevicular fluid (GCF) was collected from the deepest probing site of
      each tooth of 10 chronic periodontitis patients prior to treatment, after scaling
      and hygiene treatment, and after periodontal surgery. Surgery was carried out at
      sites which had persistent probing depths in excess of 5 mm. The patients were
      given a full periodontal examination, including measurements of probing depth,
      gingival index, bleeding index, and plaque index before each GCF collection.
      Cathepsin B/L-, elastase-, tryptase-, trypsin-, and dipeptidyl peptidase IV-like
      activities in the GCF samples were determined by fluorimetric assay with peptidyl
      derivatives of 7-amino-4-trifluoromethyl coumarin. There were reductions in all
      clinical parameters and all protease activities after scaling and hygiene
      treatment and further reductions after periodontal surgery. Decreases were
      recorded for both total enzyme activities and concentrations. The reductions were
      statistically significant in inter-patient comparisons using mean patient values
      and also in most intra-patient comparisons using site data from individual
      patients. GCF protease levels appear to reflect the clinical status of
      periodontal lesions and may prove to be of value in monitoring disease activity.

PMID- 1356149
TI  - Functional subsensitivity of 5-hydroxytryptamine1C or alpha 2 adrenergic
      heteroreceptors mediating clonidine-induced growth hormone release in the Fawn
      Hooded rat strain relative to the Wistar rat strain.
AB  - Administration of various doses of clonidine increased plasma growth hormone
      levels. Pretreatment with the alpha 2 adrenergic antagonists, yohimbine and 1-(2
      pyrimidyl)piperazine, completely blocked clonidine's effect on growth hormone
      levels. Pretreatment with the 5-hydroxytryptamine3 (5-HT3) receptor antagonist,
      MDL-72222, the 5-HT1A/5-HT2 antagonist, spiperone, and the mixed beta
      adrenergic/5-HT1B antagonists, l-propranolol and CGP361A, did not attenuate
      clonidine-induced increases in growth hormone levels. In contrast, pretreatment
      with the non-selective 5-HT1/2 antagonist, metergoline, and the 5-HT1C/5-HT2
      selective antagonist, mesulergine, reduced clonidine-induced increases in growth
      hormone levels 81 to 87% without affecting clonidine-induced decreases in
      locomotor activity. Two other 5-HT1C/5-HT2 antagonists, ritanserin and mianserin,
      also attenuated (47%) clonidine-induced increases in growth hormone levels.
      Pretreatment with the noradrenergic neurotoxin, DSP4, did not block clonidine's
      effect on growth hormone levels. Clonidine administration decreased locomotor
      activity in both the Fawn-Hooded and the Wistar rat strains to the same extent.
      On the other hand, clonidine administration failed to increase growth hormone
      levels in the Fawn-Hooded rat strain. These findings suggest that clonidine
      stimulates growth hormone secretion by activation of alpha 2 adrenergic
      heteroreceptors present on 5-HT nerve terminals which, in turn, enhance 5-HT
      activity via stimulation of postsynaptic 5-HT1C receptors to promote growth
      hormone releasing factor. Furthermore, either 5-HT1C receptors or alpha 2
      adrenergic heteroreceptors or both are functionally sub-sensitive in the Fawn
      Hooded rat strain relative to the Wistar rat strain.

PMID- 1356150
TI  - Ro 19-8022, a nonbenzodiazepine partial agonist at benzodiazepine receptors:
      neuropharmacological profile of a potential anxiolytic.
AB  - The partial agonist at benzodiazepine receptors, Ro 19-8022, has been
      characterized as a putative anxiolytic drug with an improved side effect profile.
      This orally active compound is a representative of a quinolizinone structure
      class and shows potent anticonflict activity in mice and rats. It protects
      rodents from convulsions induced by pentylenetetrazol, N-methyl-D-aspartic acid
      and maximal electroshock, as well as against audiogenic seizures, with an
      efficacy comparable to that of the full agonist alprazolam. No appreciable
      sedative or motor-impairing effects could be detected up to a very high dose (100
      mg/kg) in the horizontal wire test or the rotarod performance test in mice and
      rats and in spontaneous behavior in monkeys. Consistent with its characterization
      as a partial agonist, Ro 19-8022 antagonized the motor impairment induced by the
      full agonists diazepam or meclonazepam measured in horizontal wire and rotarod
      tests in rodents, and reduced flunitrazepam-induced effects in squirrel monkeys,
      with an efficacy comparable to that of the benzodiazepine receptor antagonist
      flumazenil. After subchronic administration of Ro 19-8022 to mice, antagonist
      precipitated withdrawal syndrome was dramatically weaker than after alprazolam
      treatment, which is indicative of a lower physical dependence liability of Ro 19
      8022. Pharmacodynamic effects recorded in convulsion and reversal of motor
      impairment tests after i.v. administration suggest a long duration of action of
      this compound. Taken together, such preclinical data suggest that benzodiazepine
      receptor partial agonists with a neurological and behavioral profile such as that
      of Ro 19-8022 may offer an innovative therapeutic approach to the treatment of
      anxiety disorders.

PMID- 1356151
TI  - Receptor-mediated toxicity of norepinephrine on cultured catecholaminergic
      neurons of the rat brain stem.
AB  - The mechanisms associated with the neurotoxic responses caused by prolonged
      exposure (48 hr) to norepinephrine (NE) were examined in cultures of brain stem
      of 18-day-old rat fetuses. Two separate components of NE neurotoxicity were
      identified and differentiated according to dose dependency, sensitivity to
      catalase and blockade by adrenoceptor antagonists. The first component of NE
      toxicity was responsible for the death of the overall cell population, affecting
      both neurons and astroblasts, and was mediated by NE auto-oxidation products.
      This toxicity was observed at high doses of NE (LD50: 100 microM), was mimicked
      by other catecholamines (epinephrine, isoproterenol, dopamine), was fully
      antagonized by catalase and could not be blocked by adrenoceptor antagonists. The
      second component of NE toxicity was specifically targeted at noradrenergic
      neurons and was mediated by alpha 1 adrenoceptors. The specific toxicity for
      noradrenergic neurons was seen at lower doses of NE (LD50: 20 microM) and
      epinephrine (LD50: 40 microM). It was mimicked by the alpha 1 agonist
      phenylephrine and blocked by the alpha antagonists prazosine and nicergoline.
      These results indicate that protracted exposure to catecholamines may be a
      possible cause of damage to noradrenergic neurons that can be prevented by alpha
      1 adrenoceptor blockade.

PMID- 1356152
TI  - Identification of the mixed disulfide of glutathione and cysteinylglycine in
      bile: dependence on gamma-glutamyl transferase and responsiveness to oxidative
      stress.
AB  - Biliary excretion of glutathione disulfide (GSSG) is used as an index of
      oxidative stress. Analysis of endogenous thiols and disulfides in rat bile by
      reverse phase high performance liquid chromatography with electrochemical
      detection revealed an unknown disulfide which eluted immediately after GSSG. This
      disulfide was tentatively identified as the mixed disulfide of glutathione (GSH)
      and cysteinylglycine (Cys-Gly), based on its coelution on a reverse phase column
      with the synthetic GS-Cys-Gly. GS-Cys-Gly was also detected in bile of other
      species. On analyzing species differences in biliary excretion of GSH-related
      thiols and disulfides, it was concluded that biliary excretion of GS-Cys-Gly was
      related to the excretion of both GSSG and Cys-Gly, which is formed from GSH by
      gamma-glutamyltransferase (gamma-GT)-catalyzed hydrolysis. Species with low
      hepatic gamma-GT (i.e., hamsters and mice) excreted little Cys-Gly in bile. These
      animals excreted negligible amounts of GS-Cys-Gly even when biliary excretion of
      GSSG was markedly increased by paraquat-induced oxidative stress. Rats and guinea
      pigs, which have high hepatic gamma-GT activities, excreted large amounts of both
      Cys-Gly and GS-Cys-Gly. Treatment of rats with acivicin, an inhibitor of gamma
      GT, decreased the biliary excretion of both Cys-Gly and GS-Cys-Gly. Paraquat
      treatment of rats resulted in an increase in GSSG excretion with concomitant
      increase of GS-Cys-Gly excretion. Rabbits, which also have high hepatic gamma-GT
      activity, excreted little GS-Cys-Gly into bile.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356153
TI  - Effect of chlorethylclonidine on arterial blood pressure and heart rate in the
      conscious rat.
AB  - The effect of chlorethylclonidine (CEC) on arterial blood pressure and heart rate
      (HR) has been evaluated in the conscious rat. CEC injection (25 mg/kg i.p.)
      caused a statistically significant decrease in mean arterial blood pressure (MAP)
      that was seen 24 hr after treatment. CEC also induced a decrease in HR that was
      maximal at 45 min but returned to pretreatment levels after 3 hr. CEC had no
      effect on the ability of isoproterenol to increase HR. CEC treatment had little
      effect on the pressor dose-response curve of either phenylephrine or BHT 920.
      When injected into the brain (25 mg/kg, lateral ventricle), CEC had no effect on
      MAP or HR. Yohimbine injected into the lateral ventricle had no effect on the
      response to i.p. CEC. Prazosin, used as a standard for comparison, caused a
      larger fall in MAP than CEC and this hypotension was associated with tachycardia
      and a marked shift (greater than 300-fold) in the phenylephrine pressor dose
      response curve. A reactive analog of prazosin, SZL-49 [1-(4-amino-6,7-dimethoxy-2
      quinazolinyl)-4-(2-bicyclo[2,2,2]octa- 2,5-diene-2-carbonyl)piperazine], had
      effects similar to prazosin on MAP and HR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356154
TI  - Characterization of [3H]quinpirole binding to D2-like dopamine receptors in rat
      brain.
AB  - The putative D2 dopamine receptor agonist quinpirole (LY 171,555) is the most
      widely used D2 agonist in in vivo and in vitro studies of D2 receptor-mediated
      effects. In addition, quinpirole may have even higher affinity for the recently
      described D3 dopamine receptor. The present study describes the in vitro binding
      properties of newly developed [3H]quinpirole in rat brain. [3H]Quinpirole binding
      was characterized in striatal membrane homogenate preparations using a filtration
      assay. Nonspecific binding was defined by 1 microM (+)-butaclamol. Specific
      [3H]quinpirole binding was saturable, and dependent on temperature, membrane
      concentration, sodium concentration and guanine nucleotides. Saturation analysis
      revealed high affinity binding characteristics (KD = 2.3 +/- 0.3 nM) which were
      confirmed by association-dissociation kinetics. The pharmacological profile of
      [3H]quinpirole binding in striatum was: (-)-N-n-propylnorapomorphine (+/-)-2
      amino-6,7-dihydroxyl-1,2,3,4-tetrahydronaphthalene greater than or equal to
      quinpirole greater than apomorphine greater than bromocriptine greater than
      dopamine greater than SKF 38393 much greater than 5-hydroxytryptamine for
      putative dopamine agonists; spiperone greater than (+)-butaclamol greater than
      haloperidol greater than (-)-sulpiride greater than clozapine greater than SCH
      23390 much greater than cinanserin for antagonists. [3H]Quinpirole binding
      exhibited stereoselectivity: (-)-sulpiride greater than (+)-sulpiride and (+)
      butaclamol greater than (-)-butaclamol. This pharmacological profile is similar,
      though-not identical, to that observed for [3H] spiperone-labeled D2 receptors.
      The regional distribution of [3H]quinpirole binding sites roughly paralleled the
      distribution of [3H]spiperone binding sites, with greatest densities present in
      the striatum, nucleus accumbens and olfactory tubercles.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1356155
TI  - [N-methyl-Tyr1,N-methyl-Arg7-D-Leu8]-dynorphin-A-(1-8)ethylamide, a stable
      dynorphin analog, produces diuresis by kappa-opiate receptor activation in the
      rat.
AB  - The i.v. administration of E-2078 ([N-methyl-Tyr1-N-methyl-Arg7-D-Leu8]-dynorphin
      A-(1-8) ethylamide) to conscious animals in doses of 15, 50 or 200 micrograms/rat
      caused a dose-related diuretic response associated with a significant in crease
      in glomerular filtration rate (GFR) and in blood pressure. The overall excretion
      of Na+ was not modified by the opioid, whereas it reduced K+ output and its
      fractional excretion. Time course studies demonstrated that the increase in GFR
      and in blood pressure were transient and did not parallel the changes in urine
      outflow. Pretreatment of the animal with 1 mg/kg of naltrexone or of naloxone
      reduced the pressor response but did not reduce the renal action of E-2078. Doses
      of naltrexone 10 times larger (10 mg/kg) were required to attenuate the diuretic
      effect and abolish completely the changes in K+ excretion; however, the increase
      in GFR was not antagonized by 10 mg/kg of naltrexone. Consonant with the studies
      in conscious rats, perfusion of isolated rat kidneys with 0.2 to 1.8 microM E
      2078 increased urine flow in a dose-dependent manner, and this effect was
      prevented by the simultaneous perfusion of 2 microM naltrexone with the peptide.
      In pentobarbital-anesthetized animals, E-2078 elicited a diuretic response that
      was not parallelled by changes in GFR or electrolyte excretion. In addition, E
      2078 caused a long lasting decrease in blood pressure which was blocked
      completely by pretreatment of the animal with 1 mg/kg of naltrexone. The diuretic
      effect of E-2078 was not modified by pretreatment of the animals with beta
      funaltrexamine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356156
TI  - Flexion characteristics of four-unit fixed partial denture frameworks using
      holographic interferometry.
AB  - Flexion of a metal/ceramic fixed partial denture (FPD) framework under function
      can cause fracture of the porcelain or deterioration of the cement seal. This
      study evaluated the flexion under compressive load of a four-unit mandibular FPD
      replacing the second premolar and the first molar. Testing was accomplished with
      elapsed time holographic interferometry, using 39 porcelain fused-to-metal
      frameworks cast with a silver-palladium alloy. The results demonstrated that
      solder joints at the junction of the premolar and molar pontics flexed under a
      reduced compressive load and exhibited a higher failure rate than other connector
      designs.

PMID- 1356157
TI  - Linear dimensional variability and tensile strengths of three solder index
      materials.
AB  - This study compared the linear dimensional change and tensile strengths of three
      indexing materials used for aligning joints to be soldered. Sixty rods 6 mm in
      diameter and 18 mm in length were made from base metal. The rods were divided
      into three groups of 10 pairs each, and a simulated solder gap was created
      between the rods in each pair. Ten simulated gaps were indexed with Duralay
      resin, 10 were indexed with Relate resin, and 10 were indexed with ZAPIT
      cyanoacrylate material. Measurements were made of each pair, before and after
      indexing, and the tensile strength of each indexed pair was measured and
      recorded. Linear measurements showed no significant difference between any of the
      groups. However, significant differences in tensile strength were found among all
      the materials tested.

PMID- 1356158
TI  - Astrocyte cultures from human embryonic brain: characterization and modulation of
      surface molecules by inflammatory cytokines.
AB  - Astrocyte-enriched cultures were established upon passaging of primary cultures
      from the myelencephalon and mesencephalon of 7-9-week-old human embryos.
      Immunocytochemical analysis showed that third-fourth passage cultures were
      composed of a highly enriched population of proliferating, epithelioid cells, up
      to 90% of which expressed glial fibrillary acidic protein (GFAP); no macrophages
      and very few fibroblasts (less than 2%) were present. GFAP expression and
      proliferation declined upon further culturing in serum-containing medium but
      could be transiently reinduced by growing the cells in a serum-free chemically
      defined medium. Large numbers of GFAP+ astrocytes were obtained from each embryo
      and could be stored frozen and recultured. Using flow cytometric analysis, human
      astrocyte cultures were examined for basal and cytokine [interferon-gamma (IFN
      gamma), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF
      alpha)]-induced expression of molecules that may be involved in astrocyte-T
      lymphocyte interactions. Cultured human astrocytes spontaneously expressed major
      histocompatibility complex (MHC) class I antigens and variable levels of MHC
      class II; MHC class I levels were increased upon IFN-gamma and TNF-alpha
      treatment, whereas MHC class II antigens were induced on most of the astrocytes
      by IFN-gamma. Among the molecules involved in antigen-independent interactions
      between T lymphocytes and target cells, lymphocyte function-associated molecule-3
      (LFA-3) was spontaneously expressed by most cultured human astrocytes, whereas
      intercellular adhesion molecule-1 (ICAM-1) was present at variable levels in non
      stimulated astrocytes and was greatly induced by IFN-gamma, TNF-alpha, and IL-1
      beta. In this study we also show that the above cytokines upregulate astroglial
      expression of adhesion molecules of the integrin family (VLA-1, VLA-2, and VLA-6)
      that may be involved in astrocyte-extracellular matrix interaction and play a
      role in the astrocyte reactive changes occurring at sites of brain injury and
      inflammation. The human astrocyte cultures developed here represent a useful in
      vitro model to further investigate mechanisms involved in bidirectional
      communication between central glia and cells of the immune system.

PMID- 1356159
TI  - Staphylococcal exotoxin superantigens induce human immunodeficiency virus type 1
      expression in naturally infected CD4+ T cells.
AB  - A high proportion of Staphylococcus aureus strains of human origin produce one or
      more exotoxins. In vivo, these toxins may give rise to a variety of clinical
      syndromes. In vitro, staphylococcal exotoxins have been shown to bind both to
      human leukocyte antigen (HLA) class II molecules on antigen-presenting cells and
      to the T-cell receptors on large fractions of T cells. The result of this
      interaction may be proliferation of the T cells, T-cell anergy, or apoptosis,
      depending on several factors, including the state of the responding cells and the
      presence of accessory molecules. Using naturally infected peripheral blood
      mononuclear cells depleted of CD8+ T cells, we have shown that staphylococcal
      exotoxins are powerful inducers of human immunodeficiency virus type 1 expression
      and that they induce expression at low concentrations and with greater efficiency
      than other T-cell mitogens. Human immunodeficiency virus type 1 was produced
      entirely by CD4+ T cells in this model; monocytes were expendable both as a
      source of virus and as a source of HLA class II molecules as long as other cells
      expressing HLA class II molecules were present. The results suggest that
      infection by S. aureus may be a cofactor in the immunopathogenesis of AIDS.

PMID- 1356160
TI  - Hantaan virus infection of human endothelial cells.
AB  - The primary pathophysiologic finding of the viral disease known as Korean
      hemorrhagic fever, the etiological agent of which is Hantaan virus (HTV), is
      vascular instability. To investigate whether HTV was able to infect cells derived
      from human vascular tissue and alter their behavior, we infected in vitro primary
      adult human endothelial cells from saphenous veins (HSVEC). We were able to
      detect the presence of viral antigens in infected cells both by
      immunofluorescence and by Western blot (immunoblot) analysis as early as day 1
      postinfection. HSVEC infected with HTV produce infectious virus during the first
      3 days of infection but, at later times (days 4 to 8), show decreasing yields of
      virus. This contrasts with the HTV growth pattern observed for the permissive
      simian CV-7 cell line, which generates infectious virus up to day 12 after
      infection. Further investigation showed that the late decrease in viral
      production in HSVEC is the result of the induction of beta interferon and can be
      reversed by the addition of anti-beta interferon serum to the culture medium. At
      no time during the course of infection of HSVEC with HTV was any obvious
      cytopathic effect observed. When tests for changes in mRNA levels of other
      cytokines and endothelial cell gene products following HTV infection of HSVEC
      were done by reverse transcription and polymerase chain reaction methods, no
      significant changes were observed in the levels of interleukin 1, interleukin 6,
      or von Willebrand factor mRNA. We hypothesize that, while HTV can replicate in
      human vascular endothelial cells, the mechanism of microvascular damage seen with
      Korean hemorrhagic fever is not likely to be a direct effect of virus replication
      but may conceivably be the consequence of an immune-mediated endothelial injury
      triggered by viral infection.

PMID- 1356163
TI  - A questionnaire study of beta-adrenergic blockade in dilated cardiomyopathy in
      Japan.
AB  - A questionnaire study on the effect of beta-blockade in dilated cardiomyopathy
      was performed. In 89 cases obtained from 24 institutions, either metoprolol (72
      patients, 41.4 +/- 29.3 mg/day, 14.1 +/- 13.2 months, mean +/- SD), propranolol
      (5 patients, 23.8 +/- 24.3 mg/day, 25.0 +/- 25.3 months), carteolol (4 patients,
      7.5 +/- 2.9 mg/day, 9.0 +/- 2.8 months) or another beta-blockers (8 patients) was
      administered. Nine patients died during the follow-up period. Overall
      effectiveness as evaluated by the attending physicians showed improvement in 51
      patients (57.3%), no change in 26 patients (29.2%), deterioration in 11 patients
      (12.4%) or was indeterminate in one patient. New York Heart Association (NYHA)
      functional class improved significantly from 2.6 to 2.3 (p less than 0.01). Heart
      rate decreased from 83.1 to 70.1 (p less than 0.01). Cardiothoracic ratio
      decreased from 55.5% to 53.9% (p less than 0.01). Left ventricular ejection
      fraction of the left ventricle measured by echocardiogram increased from 29.8% to
      37.8% (p less than 0.01). Exercise tolerance during a treadmill test and
      ventricular arrhythmias in Holter electrocardiograms improved significantly.
      There was no change in blood pressure. When the patients in different functional
      classes were compared, the patients of NYHA class III improved more frequently
      than those of NYHA class II (69% vs 53% p less than 0.01). Improvement of left
      ventricular end-diastolic dimension and left ventricular ejection fraction was
      more prominent in patients of class III than in those of class II. NYHA
      functional class and cardiothoracic ratio were significantly improved only in
      class III.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356161
TI  - Attempts to convert the cellular prion protein into the scrapie isoform in cell
      free systems.
AB  - The scrapie prion protein (PrPSc) is derived from a cellular isoform (PrPC) that
      acquires protease resistance posttranslationally. We have used several different
      experimental approaches in attempts to reconstitute in vitro the processes
      leading to protease-resistant PrPSc molecules. In the first study, we performed
      mixing experiments by adding mouse PrP 27-30 (MoPrP27-30), the protease-resistant
      core of PrPSc, to PrPC and then incubating the mixture to investigate the
      possibility of heterodimer formation as a first step in prion replication. We
      used epitopically tagged PrP molecules, synthesized in murine neuroblastoma (N2a)
      cells transfected with the chimeric mouse/Syrian hamster MHM2 PrP construct,
      which are recognized by the Syrian hamster-specific monoclonal antibody 3F4.
      After as long as 24 h of incubation, the reaction mixture was assayed for
      heterodimeric intermediates of MHM2 PrPC and MoPrPSc and for protease-resistant
      3F4-reactive PrP. We were unable to identify any aggregates of MHM2 PrPC and
      MoPrPSc on immunoblots; furthermore, we did not observe de novo formation of
      protease-resistant MHM2 PrP. In a second study, MoPrPC was metabolically
      radiolabeled in scrapie prion-infected N2a cultured cells, and then the cell
      extract was homogenized and incubated under various conditions to allow for the
      formation of protease-resistant MoPrPSc. We observed no radiolabeled MoPrPSc by
      immunoprecipitation after as long as 24 h of in vitro incubation. In a third
      approach, Syrian hamster PrP (SHaPrP) was synthesized in a cell-free translation
      system supplemented with microsomal membranes derived from either normal or
      scrapie prion-infected cultured cells. We found that all SHaPrP species
      translocated across microsomal membranes from scrapie prion-infected cells were
      protease sensitive in the presence of detergents and displayed the same topology
      as those generated by microsomes from normal cells or from dog pancreas. We also
      studied PrP molecules that encode the codon 102 mutation that causes the rare
      human prion disease Gerstmann-Straussler-Scheinker (GSS) syndrome. On the basis
      of our data, GSSPrP appears to yield topological forms similar to those of the
      wild-type PrP when processed by either normal or scrapie prion-derived
      microsomes.

PMID- 1356162
TI  - Modulation of cellular and viral promoters by mutant human p53 proteins found in
      tumor cells.
AB  - Wild-type p53 has recently been shown to repress transcription from several
      cellular and viral promoters. Since p53 mutations are the most frequently
      reported genetic defects in human cancers, it becomes important to study the
      effects of mutations of p53 on promoter functions. We, therefore, have studied
      the effects of wild-type and mutant human p53 on the human proliferating-cell
      nuclear antigen (PCNA) promoter and on several viral promoters, including the
      herpes simplex virus type 1 UL9 promoter, the human cytomegalovirus major
      immediate-early promoter-enhancer, and the long terminal repeat promoters of Rous
      sarcoma virus and human T-cell lymphotropic virus type I. HeLa cells were
      cotransfected with a wild-type or mutant p53 expression vector and a plasmid
      containing a chloramphenicol acetyltransferase reporter gene under viral (or
      cellular) promoter control. As expected, expression of the wild-type p53
      inhibited promoter function. Expression of a p53 with a mutation at any one of
      the four amino acid positions 175, 248, 273, or 281, however, correlated with a
      significant increase of the PCNA promoter activity (2- to 11-fold). The viral
      promoters were also activated, although to a somewhat lesser extent. We also
      showed that activation by a mutant p53 requires a minimal promoter containing a
      lone TATA box. A more significant increase (25-fold) in activation occurs when
      the promoter contains a binding site for the activating transcription factor or
      cyclic AMP response element-binding protein. Using Saos-2 cells that do not
      express p53, we showed that activation by a mutant p53 was a direct enhancement.
      The mutant forms of p53 used in this study are found in various cancer cells. The
      activation of PCNA by mutant p53s may indicate a way to increase cell
      proliferation by the mutant p53s. Thus, our data indicate a possible functional
      role for the mutants of p53 found in cancer cells in activating several important
      loci, including PCNA.

PMID- 1356164
TI  - The effects of phentolamine and nitroglycerin on right-sided hemodynamics in
      cardiac patients can be explained by a shift of the systemic venous return curve
      and right-ventricular output curve.
AB  - The present study investigated the effects of phentolamine (PH) and nitroglycerin
      (NG) on the hemodynamics of the right heart in patients with cardiac disease. The
      patients were divided into a well-functioning left heart group (W group, n = 15)
      and a poorly-functioning left heart group (P group, n = 15). Right cardiac
      hemodynamic parameters and plasma noradrenaline (NA) and adrenaline (A)
      concentrations were measured before and after administering PH (0.1 mg/kg, i.v.)
      or NG (0.6 mg, sublingual). In a parallel animal study we obtained a systemic
      venous return curve by measuring mean circulatory pressure (MCP), mean right
      atrial pressure (RAP) and cardiac output, before and after administering PH (0.1
      mg/kg, i.v.) or NG (12.5 micrograms/kg, i.v.) to anesthetized open-chest dogs (n
      = 14). We used MCP data (W group: 7.5 mmHg, P group: 10 mmHg) obtained in a
      separate series of human studies in our laboratory. We constructed the venous
      return curve by connecting the MCP point on abscissa with the cardiac index (CI)
      RAP plot obtained in the clinical study. We also constructed the right
      ventricular output curve by connecting the point of -2 mmHg on the abscissa with
      the CI-RAP plot. We obtained the following results: (1) PH shifted the CI-RAP
      plot to the left and upwards, while NG shifted the CI-RAP plot to the left almost
      horizontally on the CI-RAP plane, where CI was plotted on ordinate and RAP on
      abscissa. The length [formula: see text] C = control point, PH = point after PH)
      of the shift of CI-RAP plot due to PH was greater in the P group than in W group,
      while there was no difference in the length [formula: see text] C = control
      point, NG = point after NG) of the shift of CI-RAP plot due to NG between P and W
      groups. (2) Both PH and NG significantly elevated plasma NA and A concentrations
      in both the W and P groups. In the P group, PH increased the plasma NA
      concentration significantly more than did NG, but both drugs increased plasma A
      concentration to a similar extent. (3) Both PH and NG significantly decreased the
      mean pulmonary arterial pressure with NG doing so significantly more than
      PH.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1356165
TI  - Differing actions of endothelin-1 on canine systemic resistance and capacitance
      vessels.
AB  - In anesthetized open-chest dogs, an intravenous bolus injection of endothelin-1
      (ET-1, 400 pmol/kg) caused transient hypotension (initial hypotensive phase;
      phase 1), followed by a continuous elevation of blood pressure (late hypertensive
      phase; phase 2). The constriction and dilation of the systemic capacitance and
      resistance vessels were evaluated from the change in mean circulatory pressure
      (MCP) and in total peripheral resistance (TPR) in phases 1 and 2. To examine the
      modification of the action of ET-1 on the blood vessels by the baroceptor reflex
      or by the endothelium-derived relaxing factor (EDRF) released by ET-1 in phase 1,
      we performed experiments in dogs under total spinal anesthesia (TSA group),
      methylene blue-treated dogs (MB group) as well as in the untreated dogs (control
      group). ET-1 decreased the TPR significantly, and increased the MCP significantly
      in phase 1 in the control (n = 8) and TSA (n = 8) groups; there was no difference
      between the groups. ET-1 had no significant effect on TPR but increased the MCP
      significantly in MB group (n = 8) during phase 1. The percentage increase of MCP
      in the MB group significantly exceeded that of the control group. ET-1 increased
      both the TPR and MCP significantly in phase 2 in the control group (n = 8). This
      study indicated that the vasoconstrictor action of ET-1 on the systemic
      capacitance vessels in phase 1 did not result from a baroceptor reflex, and that
      the vasodilator action of ET-1 on the systemic resistance vessels may be at least
      in part mediated via EDRF released by ET-1. We suggest that the vasoconstrictor
      action of ET-1 on the systemic capacitance vessels is strong, but the vasodilator
      action of EDRF on the systemic capacitance vessels is weak.

PMID- 1356167
TI  - [Assistance: the handiwork and art].
AB  - The problems of assistance are still not the subject of comprehensive discussion,
      at the same time perfection of assistance is an important link of surgery
      perfection. Questionnaires containing 120 basic questions were sent to 120
      surgeons of the country; 73 representatives of academic and practical surgery
      responded. Analysis of answers and recommendations, which were not always
      unambiguous, allowed the problem to be considered in a wider aspect and a rich
      collective and individual experience to be critically comprehended. Optimization
      of the activity of assistants, their skilled handiwork, and the skill in teaching
      and learning surgery in the interest of a sick person are dwelt on.

PMID- 1356166
TI  - [Two kindreds with familial Alzheimer's disease--analysis of the APP717 mutation
      and the mutated genes for the prion protein].
AB  - Numerous Caucasian familial Alzheimer's disease (FAD) pedigrees have been
      described in the literature, while only 21 Japanese FAD families have been
      reported to date. Here we report the clinical findings and the result of
      molecular genetic analysis of 4 patients from two FAD kindreds, OS-2 and OS-3.
      The proband in OS-2 family has developed loss of recent memory and place
      disorientation age at 43. A brain CT showed severe diffuse cortical atrophy. Her
      younger brother had dementia at 42 years and her mother and other 3 siblings had
      also dementia symptoms suspected to be Alzheimer's disease. The proband in OS-3
      family showed declining recent memory at 49 years and developed dysphagia, gait
      disturbance and emotional incontinent with cerebral atrophy at 52 years. His
      father and elder brother demonstrated dementia signs at 60 and 54 years old,
      respectively. Recently it was reported that affected members from 2 Caucasian
      kindreds with FAD had missense mutation in exon 17 of the gene for amyloid
      precursor protein (APP). Patients from three different Japanese kindreds with FAD
      also showed the same mutation on the APP gene. Amino acid substitution (Val-Ile)
      at codon 717 by this mutation is responsible for FAD in at least some kindreds.
      We used genomic DNA from 4 affected members of 2 families to determine whether
      the disease in these families is associated with a APP717 mutation and the
      mutated codons, 102, 117, 129, 178 and 200, on the gene for protease-resistance
      prion protein (PrP) which cause transmissible dementia, Creutzfelt-Jacob disease
      (CJD) and Gerstmann-Strausler syndrome (GSS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356168
TI  - DNA-based presymptomatic diagnosis of Wilson disease.
AB  - Investigation using DNA markers in a family with Wilson disease revealed that an
      apparently normal child of 10 years of age with non-diagnostic copper
      biochemistry had the disease. The procedure used linked restriction fragment
      length polymorphic markers. Demonstration of increased liver copper concentration
      from a liver biopsy confirmed the diagnosis and the child was started on
      chelation therapy. Two other asymptomatic siblings were shown, using the same
      techniques, not to have the disease. Similar analysis was carried out on another
      family with just one index case.

PMID- 1356169
TI  - Molecular basis of inherited medium-chain acyl-CoA dehydrogenase deficiency
      causing sudden child death.
AB  - Deficiency of medium-chain acyl-CoA dehydrogenase (MCAD) is an important cause of
      sudden death in children. The majority of surviving individuals with MCAD
      deficiency studied to date are homozygous for a single point mutation at bp 985
      of the MCAD mRNA (A985G). We have now identified a four-base-pair deletion in
      exon 11 of one allele of the MCAD gene in an American child who died of MCAD
      deficiency. The deletion mutation results in a frameshift and premature
      termination codon in the mutant MCAD mRNA. The second mutant allele contained the
      common point mutation A985G, and thus the proband was a compound heterozygote.
      Protein immunoblot analysis of the child's liver proteins revealed that the
      mutant MCAD proteins were barely detectable. Allele-specific oligonucleotide
      hybridization analysis performed on amplified exon 11 of the child's MCAD gene
      clearly identified both mutations. MCAD RFLP analysis of the patient's DNA
      revealed heterozygosity at the Taq I MCAD RFLP site, thus, the two mutations are
      associated with different haplotypes. Therefore, we have identified a new
      mutation in the MCAD gene and have developed a nucleic-acid-based screening
      approach which allows the post mortem identification of MCAD deficiency.

PMID- 1356170
TI  - Gene analysis of Mennonite maple syrup urine disease kindred using primer
      specified restriction map modification.
AB  - Maple syrup urine disease (MSUD) is an autosomal recessive inherited disease due
      to a deficiency of any of the subunits, E1 alpha, E1 beta or E2, of the branched
      chain alpha-ketoacid dehydrogenase complex (BCKDH). A large Mennonite kindred of
      MSUD has been studied in Pennsylvania, USA. In the present investigation, genomes
      from 70 members, including 12 patients belonging to eight different Mennonite
      MSUD pedigrees, were examined for possible abnormalities in the E1 alpha gene of
      BCKDH, by primer-specified restriction map modification. A T-to-A substitution
      which generates an asparagine in place of a tyrosine at amino acid 394 of the
      mature E1 alpha subunit was present in both alleles in all the patients and in a
      single allele in all obligate carriers and several siblings. We describe a new
      technique for rapid and easy detection of the mutant gene in this population.
      These family studies provide additional evidence that Mennonite MSUD is caused by
      a missense mutation of the E1 alpha gene of BCKDH

PMID- 1356171
TI  - Hereditary tyrosinaemia type II in a consanguineous Ashkenazi Jewish family:
      intrafamilial variation in phenotype; absence of parental phenotype effects on
      the fetus.
AB  - We describe an Ashkenazi Jewish family in which two adults, offspring of
      consanguineous parents, have persistent hypertyrosinaemia (770-1110 mumol/L;
      normal less than 110 mumol/L). The metabolic disorder in this family is
      apparently due to hepatic cytosolic tyrosine aminotransferase deficiency
      (hereditary tyrosinaemia, type II; McKusick, 276600), because it is associated
      with the oculocutaneous manifestations of Richner-Hanhart syndrome. The
      association of this syndrome with hereditary tyrosinaemia type II is presumed to
      be constant. It is not in this family. The affected female sib (age 41 years) has
      hypertyrosinaemia and oculocutaneous signs; the brother (age 39 years) has
      hypertyrosinemia but no oculocutaneous disease. Both sibs have two children; none
      has signs of a metabolic fetopathy. Maternal hypertyrosinaemia and maternal
      hyperphenylalaninaemia evidently constitute different risk factors for the fetus.
      Paternal hypertyrosinaemia is apparently not a risk to male infertility.

PMID- 1356172
TI  - Prospective versus clinical diagnosis and therapy of acute neonatal
      hyperammonaemia in two sisters with carbamyl phosphate synthetase deficiency.
AB  - Two female siblings were treated for acute neonatal hyperammonaemia due to
      complete carbamyl phosphate synthetase I deficiency. The first child was detected
      clinically at 65 hours of age and therapy started at 79 hours. The second child
      was followed from birth and therapy started at 5 hours of age. The extrapolated
      rate of increase of blood ammonia, in the first hours of life before therapy
      started, was 19 mumol L-1 h-1 in both babies. Peak blood ammonia level was 2235
      mumol/L in the first (clinically detected) child and 271 mumol/L in the second
      (prospectively followed) child. The second child became symptomatic at 3 hours of
      age when blood ammonia level was as low as 90 mumol/L, whereas blood ammonia
      levels above 100 mumol/L caused no symptoms during recovery. The child detected
      clinically required haemodialysis and peritoneal dialysis to treat the
      hyperammonaemia. In the prospectively treated child, early therapy with
      intravenous sodium benzoate and sodium phenylacetate slowed the rate of increase
      in blood ammonia level, but this therapy did not prevent the need for peritoneal
      dialysis.

PMID- 1356173
TI  - Mechanisms of increased hepatic glutamine uptake in the endotoxin-treated rat.
AB  - The mechanisms underlying the accelerated hepatic consumption of glutamine that
      occurs during endotoxemia were investigated in rats 12 hr after treatment with
      Escherichia coli lipopolysaccharide. Hepatic glutamine delivery and consumption
      were calculated from measurements of hepatic blood flow and blood glutamine
      levels. Hepatic glutaminase activity and glutamine and glutamate content were
      determined. Hepatocyte plasma membrane transport activity was evaluated employing
      isolated hepatic plasma membrane vesicles (HPMVs). Endotoxin treatment resulted
      in an 11-fold increase in hepatic glutamine consumption and a 2-fold increase in
      the delivered load of glutamine to the liver. Hepatic glutamate content doubled
      while glutamine content was unaffected, not withstanding a decrease in the
      specific activity of glutaminase. Studies employing HPMVs demonstrated that
      hepatic plasma membrane transport activity was unaffected by endotoxin treatment.
      The enhanced hepatic consumption of glutamine secondary to endotoxemia appears to
      be the result of both a mass-action effect and the concurrent activation of
      intracellular metabolism. Responses at the level of plasma membrane transport do
      not appear to play an active role in mediating this enhanced hepatic uptake.

PMID- 1356174
TI  - Push-pull cannula for localized application of drugs and sampling of medium,
      combined with electrophysiological recordings in an interface slice chamber.
AB  - These experiments combined electrophysiological recordings from hippocampal
      slices with application of drugs to and sampling of extracellular fluid from a
      restricted region of the slice using a push-pull cannula placed under the slice
      in an interface chamber. Stable and apparently normal extracellular and
      intracellular recordings could be obtained directly over the tip of the cannula
      and solutions changed without disturbing the recording. Relatively rapid effects
      (1-5 min) were observed when TTX, CNQX, or medium containing 50 mM K+ were
      applied via the cannula and recovery from these effects was achieved. In
      addition, effects were restricted to the immediate vicinity of the cannula;
      neurones recorded several hundred micrometers away were apparently unaffected.
      Samples of extracellular fluid obtained as minute fractions during the
      application of high K+ containing medium contained higher concentrations of GABA,
      aspartate and glutamate than control fractions but the same levels of other amino
      acids, e.g., isoleucine and leucine. With appropriate design of push-pull cannula
      and recording chamber, therefore, stable electrophysiological recordings can be
      combined with localized extracellular fluid sampling and rapid and localized
      application of test solutions in an interface slice chamber.

PMID- 1356175
TI  - Controlled trial of pulse methylprednisolone versus two regimens of pulse
      cyclophosphamide in severe lupus nephritis.
AB  - Pulse cyclophosphamide is more effective than prednisone alone in preventing
      renal failure in lupus nephritis. We undertook a randomised, controlled trial to
      find out whether pulse methylprednisolone could equal pulse cyclophosphamide in
      preserving renal function in patients with lupus nephritis, and whether there was
      a difference between long and short courses of pulse cyclophosphamide in
      preventing exacerbations. 65 patients (60 female, 5 male; median [range] age 29
      [10-48] years) with severe lupus nephritis were assigned randomly to monthly
      pulse methylprednisolone for 6 months (25 patients), monthly pulse
      cyclophosphamide for 6 months (20), or monthly cyclophosphamide for 6 months
      followed by quarterly pulse cyclophosphamide for 2 additional years (20).
      Patients treated with pulse methylprednisolone had a higher probability of
      doubling serum creatinine than those treated with long-course cyclophosphamide (p
      less than 0.04). Risk of doubling creatinine was not significantly different
      between short and long course cyclophosphamide. However, patients treated with
      short-course cyclophosphamide had a higher probability of exacerbations than
      those treated with long-course cyclophosphamide (p less than 0.01). An extended
      course of pulse cyclophosphamide is more effective than 6 months of pulse
      methylprednisolone in preserving renal function in patients with severe lupus
      nephritis. Addition of a quarterly maintenance regimen to monthly pulse
      cyclophosphamide reduces the rate of exacerbations.

PMID- 1356176
TI  - Placebo-controlled trial of prednisolone in children intubated for croup.
AB  - Many studies have attempted to find out whether steroid treatment is beneficial
      in children with croup, but the results have been inconclusive. We have done a
      prospective placebo-controlled study of the effect of prednisolone on two
      clinical endpoints--the duration of intubation and the need for reintubation.
      Reasons for exclusion were age under 6 months, congenital airway anomalies, and
      previous intubation. 70 eligible children were randomly assigned treatment with
      prednisolone 1 mg/kg (n = 38) or placebo (n = 32) every 12 h given by nasogastric
      tube until 24 h after extubation. 11 (34%) placebo-treated and only 2 (5%)
      prednisolone-treated patients required reintubation after accidental or elective
      extubation (p = 0.004, Fisher's exact test; odds ratio 8.9, 95% confidence
      interval 1.7-59.3). Survival analysis with log-normal regression showed that the
      duration of intubation was shorter with steroid therapy (p less than 0.003) and
      increasing age (p less than 0.02), but was not influenced by endotracheal tube
      size or abnormality on chest radiograph. The median duration of intubation was
      138 (95% CI 118-160) h in children who received placebo and 98 (85-113) h in the
      prednisolone group. Steroid therapy reduces the duration of intubation and the
      need for reintubation in children intubated for croup.

PMID- 1356177
TI  - Humanised monoclonal antibody therapy for rheumatoid arthritis.
AB  - Monoclonal antibodies that target T cells have shown some benefit in rheumatoid
      arthritis although responses have not been long lasting. This is partly due to
      insufficient therapy consequent upon antibody immunogenicity. Use of humanised
      antibodies, which are expected to be less foreign to man than conventional rodent
      antibodies, might overcome this problem. We therefore assessed in a phase 1 open
      study the potential of a "lymphocyte depleting" regimen of the humanised
      monoclonal antibody CAMPATH-1H in 8 patients with refractory rheumatoid
      arthritis. Apart from symptoms associated with first infusions of antibody,
      adverse effects were negligible. Significant clinical benefit was seen in 7
      patients, lasting for eight months in 1. After one course of therapy, there was
      no measurable antiglobulin response, although 3 out of 4 patients have become
      sensitised on retreatment. Humanisation reduces the immunogenicity of rodent
      antibodies but anti-idiotype responses may still be seen on repeated therapy,
      even in patients sharing immunoglobulin allotype with the humanised antibody.

PMID- 1356178
TI  - Maternal relaxin concentrations in diabetic pregnancy.
AB  - Maternal serum concentrations of relaxin, an insulin homologue produced both by
      the corpus luteum of pregnancy and by the fetoplacental unit, are highest in the
      first trimester and fall to their lowest level in the third trimester. Relaxin is
      thought to influence carbohydrate metabolism in the uterus, and it has been
      suggested that serum concentrations of relaxin in diabetic women are higher than
      those of non-diabetic women. We show that maternal serum relaxin concentrations
      are significantly higher at each stage of pregnancy in insulin-dependent diabetic
      mothers than in non-diabetic mothers. This elevation in relaxin concentrations is
      not related to other indices of diabetic control. The physiological importance of
      the higher concentrations of relaxin in the serum of diabetic women--in
      particular, whether they contribute to the higher incidence of major anomalies in
      the fetuses of diabetic mothers--is yet to be determined.

PMID- 1356179
TI  - Prevention of Yersinia enterocolitica growth in red-blood-cell concentrates.
AB  - In response to concern about Yersinia enterocolitica contamination of blood
      products, we have studied the effects on Y enterocolitica growth of holding whole
      blood at 22 degrees C for 20 h and then removing leucocytes. Thirty pools of
      three bags of blood were inoculated with Y enterocolitica (2 x 10(1)-3 x 10(4)
      colony-forming units/ml). One bag in each pool was processed to red-blood-cell
      concentrate after 6 h at 4 degrees C (RBC); the other two were held at 22 degrees
      C for 20 h before processing to buffy-coat-depleted RBC (BCd-RBC). One of these
      bags was then depleted of leucocytes by filtration (Ld-RBC). All bags were stored
      at 4 degrees C for 5 weeks. RBC bags showed Y enterocolitica growth after the
      shortest storage times, followed by BCd-RBC then Ld-RBC (p less than 0.03-0.001).
      We recommend that whole blood should be held at 22 degrees C to make use of
      inherent bactericidal activity; leucocytes should then be removed.

PMID- 1356180
TI  - The final autonomy.

PMID- 1356181
TI  - How can one assess damage caused by treatment of childhood cancer?

PMID- 1356182
TI  - Diagnosing juvenile myoclonic epilepsy.

PMID- 1356183
TI  - Developmental biology: impact on medicine.

PMID- 1356184
TI  - Stress failure of pulmonary capillaries: role in lung and heart disease.
AB  - Pulmonary capillaries have extremely thin walls to allow rapid exchange of
      respiratory gases across them. Recently it has been shown that the wall stresses
      become very large when the capillary pressure is raised, and in anaesthetised
      rabbits, ultrastructural damage to the walls is seen at pressures of 40 mm Hg and
      above. The changes include breaks in the capillary endothelial layer, alveolar
      epithelial layer, and sometimes all layers of the wall. The strength of the thin
      part of the capillary wall can be attributed to the type IV collagen in the
      extracellular matrix. Stress failure of pulmonary capillaries results in a high
      permeability form of oedema, or even frank haemorrhage, and is apparently the
      mechanism of neurogenic pulmonary oedema and high-altitude pulmonary oedema. It
      also explains the exercise-induced pulmonary haemorrhage that occurs in all
      racehorses. Several features of mitral stenosis are consistent with stress
      failure. Overinflation of the lung also leads to stress failure, a common cause
      of increased capillary permeability in the intensive care environment. Stress
      failure also occurs if the type IV collagen of the capillary wall is weakened by
      autoantibodies as in Goodpasture's syndrome. Neutrophil elastase degrades type IV
      collagen and this may be the starting point of the breakdown of alveolar walls
      that is characteristic of emphysema. Stress failure of pulmonary capillaries is a
      hitherto overlooked and potentially important factor in lung and heart disease.

PMID- 1356185
TI  - Simplification of antibiotic dose adjustments in renal insufficiency: the DREM
      system.
AB  - Many clinicians, unassisted by reference books, are unable to make the required
      dose adjustment of antibiotics needed when a patient has renal insufficiency. We
      describe the DREM (dosing in renopathy by easy-to-use multipliers) system, which
      simplifies the understanding and the process of dose adjustment. DREM is a two
      step process: Cockcroft and Gault estimation of creatinine clearance (CLcr) from
      age, sex, and serum creatinine and calculation of the adjusted dose or dosing
      interval by multipliers. If the normal dose is multiplied by the dose multiplier
      (CLcr/100) and the dosing interval by the interval multiplier (100/CLcr), the
      adjusted dose and interval, respectively, are obtained. Theoretical trough
      concentrations calculated with the DREM system correlated closely (r = 0.9) with
      actual concentrations obtained from doses calculated by the Hull and Sarubbi
      method in 23 patients. With DREM, gentamicin or tobramycin trough concentrations
      above 2 micrograms/ml were less likely to occur. The DREM system is a simple and
      easily remembered method for dose adjustments of certain anti-infective agents in
      renal insufficiency. Dose estimates with this method are reasonably accurate and
      compare favourably with other standard methods of correction.

PMID- 1356186
TI  - Early detection of antibodies to HIV-1 by third-generation assays.
AB  - Third-generation immunoassays for detection of antibody to human immunodeficiency
      virus (HIV) have reduced the interval between infection and antibody detection.
      Might such earlier detection diminish the value of the western blot as a
      confirmatory assay? We compared the sensitivity of one second-generation and two
      third-generation anti-HIV enzyme immunoassays (EIAs) with the results from HIV
      antigen testing and western blot. 1045 western-blot confirmed anti-HIV positive
      samples were tested with a detection rate of 100% for all three EIAs. The
      detection rate in 36 samples drawn from different persons in early stages of HIV
      infection was 89% for the second-generation EIA and 94% for both third-generation
      EIAs. With carefully selected seroconversion panels that included sampling
      intervals during seroconversion of one week or less, we found that both third
      generation EIAs detected seroconversion on average 5 days earlier (range 0-13)
      than did the second-generation assay. Western blot is commonly used to confirm
      HIV infection. In 6 of 10 seroconversions, one or both third-generation EIAs were
      reactive before any band appeared in the western blot. Since HIV antigen was
      detectable in these cases, the HIV antigen test may serve as a confirmatory assay
      for anti-HIV EIA-positive, western-blot negative, samples.

PMID- 1356187
TI  - Two paths for medical practice.

PMID- 1356188
TI  - Euthanasia: doctor convicted of attempted murder.

PMID- 1356189
TI  - Mumps meningitis and measles, mumps, and rubella vaccine.

PMID- 1356190
TI  - Diagnosis of recurrent suffocation of children.

PMID- 1356191
TI  - Faecal excretion of hepatitis E virus.

PMID- 1356192
TI  - Intracisternal A-type retroviruses and immune dysfunctions.

PMID- 1356193
TI  - Failure of low-dose dapsone-pyrimethamine in primary prophylaxis of Pneumocystis
      carinii pneumonia.

PMID- 1356194
TI  - Wet vacuum-cleaning and housedust-mite allergen.

PMID- 1356195
TI  - Magnetic resonance imaging in epilepsy.

PMID- 1356196
TI  - Improvement in seizures after ivermectin.

PMID- 1356198
TI  - Novel delivery system for continuous desferrioxamine infusion in iron-overloaded
      patients.

PMID- 1356197
TI  - Xerostomia associated with didanosine.

PMID- 1356199
TI  - Vaginal chlorhexidine disinfection during labour.

PMID- 1356200
TI  - Vaginal chlorhexidine disinfection during labour.

PMID- 1356201
TI  - Sensitivity of QBC malaria test.

PMID- 1356202
TI  - Dairy fat intake in Finland.

PMID- 1356203
TI  - Transmission of hepatitis in haemophiliacs.

PMID- 1356204
TI  - Gender and depression.

PMID- 1356205
TI  - Gender and depression.

PMID- 1356206
TI  - Predictably dangerous psychopaths.

PMID- 1356207
TI  - Demand for hospital delivery services in Ireland.

PMID- 1356208
TI  - Discounting health care.

PMID- 1356209
TI  - Healing rituals and sacred serpents.

PMID- 1356210
TI  - Fuzzy logic and waiting lists.

PMID- 1356211
TI  - Distortion of HLA gene transmission in childhood-onset myasthenia gravis.

PMID- 1356212
TI  - Journals for developing countries.

PMID- 1356213
TI  - Myocardial hibernation.

PMID- 1356214
TI  - Intra-aortic balloon pumping by femoro-femoral cardiac support in cardiac failure
      after coronary bypass.

PMID- 1356215
TI  - X-ray mammography and breast compression.

PMID- 1356216
TI  - Antiviral response to tamoxifen.

PMID- 1356217
TI  - Ultrasonography of benign adrenal tumours.

PMID- 1356218
TI  - BCG vaccination in children born to HIV-positive mothers.

PMID- 1356219
TI  - Maternal serum screening policy for Down's syndrome.

PMID- 1356220
TI  - BCG vaccination in children born to HIV-positive mothers.

PMID- 1356221
TI  - Bungee-jumping and design of experiments.

PMID- 1356222
TI  - BCG vaccination in children born to HIV-positive mothers.

PMID- 1356223
TI  - Metabolic compartmentation of vertebrate glutamine synthetase: putative
      mitochondrial targeting signal in avian liver glutamine synthetase.
AB  - The evolution of uricoteley as a mechanism for hepatic ammonia detoxication in
      vertebrates required targeting of glutamine synthetase (GS) to liver mitochondria
      in the sauropsid line of descent leading to the squamate reptiles and archosaurs.
      Previous studies have shown that in birds and crocodilians, sole survivors of the
      archosaurian line, hepatic GS is translated without a transient, N-terminal
      targeting signal common to other mitochondrial matrix proteins. To identify a
      putative internal targeting sequence in the avian enzyme, the amino acid sequence
      of chicken liver GS was derived by a combination of sequencing of cloned cDNA,
      direct sequencing of mRNA, and sequencing of polymerase chain reaction (PCR)
      products amplified from reverse-transcribed mRNA. Analysis of the first 20 or so
      N-terminal amino acids of the derived sequence for the chicken enzyme shows that
      they are devoid of acidic amino acids, contain several hydroxy amino acids, and
      can be predicted to form a positively charged, amphipathic helix, all of which
      are characteristic properties of mitochondrial targeting signals. A comparison of
      the N-terminus of chicken GS with the N-termini of cytosolic mammalian GSs
      indicates that at least three amino acid replacements may have been responsible
      for converting the N-terminus of the cytosolic mammalian enzyme into a
      mitochondrial targeting signal. Two of these, His15 and Lys19, result in
      additional positive charges, as well as in changes in hydrophilicity. Both could
      have resulted from third-base-codon substitutions. A third replacement, Ala12,
      may contribute to the helicity of the N-terminus of the chicken enzyme. The N
      terminus of the cytosolic chicken brain GS (positions 1-36) was found to be
      identical to that of the liver enzyme. The complete sequence of chicken retinal
      GS is also identical to that of the liver enzyme. GS is coded by a single gene in
      birds, so these sequence data suggest that, unlike the situation in other tissue
      specific compartmental isozymes, differential targeting of avian GS to the
      mitochondrial or cytosolic compartments is not dependent on the sequence of the
      primary translation product of its mRNA but may involve some other tissue
      specific factor(s).

PMID- 1356224
TI  - U-M Cancer Center embarks on ovarian cancer drug study.

PMID- 1356225
TI  - Glutamate-induced energetic stress in hippocampal slices: evidence against NMDA
      and glutamate uptake as mediators.
AB  - The introduction of exogenous glutamate to normally respiring hippocampal slices
      produced substantial reductions in ATP, phosphocreatine (PCr) and intracellular
      pH (pHi) when the concentration exceeded 1 mM. These changes were not prevented
      by addition of MK-801 (an NMDA receptor antagonist), nor were they mimicked by
      NMDA or high potassium. In addition, the glutamate-induced metabolic alterations
      were not prevented by addition of aspartate-b-hydroxymate or sodium substitution
      by choline, both of which should inhibit high-affinity sodium-dependent glutamate
      uptake. These results suggest that glutamate alone can produce marked energetic
      stress in neural tissue, even when glucose and oxygen are maintained at control
      levels; and that the energetic stress does not appear to be specifically mediated
      by NMDA-induced depolarization, or by high-affinity uptake of glutamate.

PMID- 1356227
TI  - Molecular typing of Helicobacter pylori by chromosomal and plasmid DNA
      organization.
AB  - Diverse strains of Helicobacter pylori were examined in order to initiate a
      molecular epidemiological typing scheme for this agent of human gastritis. Twelve
      differently-sized plasmids from 1.8 to 63 kbp were identified in those strains
      harbouring extrachromosomal DNA. Recombinant DNA probes were cloned randomly from
      the chromosome of the (plasmid-free) type strain (NCTC 11637), and used to probe
      genomic Southern blots for restriction site variation in and around homologous
      loci. Genus-specific probe DNAs were obtained which grouped strains on the bases
      of DNA base substitution or rearrangements. On the basis of the four probes
      examined, all strains exhibited intraspecific chromosomal divergence, indicating
      that H. pylori is highly diverse genetically, but nonetheless susceptible to
      chromosome and plasmid molecular typing.

PMID- 1356226
TI  - Thy-1 modulation and cell proliferation at early steps of intrathymic bone marrow
      cell differentiation.
AB  - Intrathymic (IT) transfer of bone marrow (BM) precursor cells in sublethally
      irradiated hosts has been widely used to study T cell differentiation and
      maturation. In this report we have used double congenic mice Ly 5.1 Thy 1.1
      (host) and Ly 5.2 Thy 1.2 (donor) and detected cycling Ly 5.2+ BM cells by in
      vivo bromodeoxyuridine incorporation, before induction of the Thy 1.2 antigen.
      Until Day 9 post-transfer, some donor type cells express a high level of Thy 1.2
      together with macrophage and granulocyte markers. A few days later, a Thy 1.2low
      population transiently B220+ was detected. Thereafter, donor type cells expressed
      an intermediate Thy 1.2 brightness; this population then persisted and surpassed
      the other subsets. Our findings permitted to establish a relationship between
      cell cycle and Thy 1 fluorescence intensity according to the sequence: Thy 1low
      resting, Thy 1low cycling, Thy 1high cycling, Thy 1high resting. Moreover, we
      have shown that cells from the myeloid and B lineages can, in vivo, transiently
      express the Thy 1 antigen, develop and differentiate within the thymus
      microenvironment.

PMID- 1356228
TI  - Is health education effective?

PMID- 1356229
TI  - Molecular identification of the gene responsible for congenital nephrogenic
      diabetes insipidus.
AB  - Antidiuretic hormone (arginine vasopressin) binds to and activates V2 receptors
      in renal collecting tubule cells. Subsequent stimulation of the Gs/adenylyl
      cyclase system promotes insertion of water pores into the luminal membrane and
      thereby reabsorption of fluid. In congenital nephrogenic diabetes insipidus
      (CNDI), an X-linked recessive disorder, the kidney fails to respond to arginine
      vasopressin. Here we report that an affected male of a family with CNDI has a
      deletion in the open reading frame of the V2 receptor gene, causing a frame shift
      and premature termination of translation in the third intracellular loop of the
      receptor protein. A normal receptor gene was found in the patient's brother. Both
      the normal and the mutant allele were detected in his mother. A different
      mutation, causing a codon change in the third transmembrane domain of the V2
      receptor, was found in the open reading frame of an affected male but not in the
      unaffected brother belonging to another family suffering from CNDI.

PMID- 1356230
TI  - Centractin is an actin homologue associated with the centrosome.
AB  - Actin is one of the most ubiquitous, abundant and well-conserved proteins of
      eukaryotes, participating in many crucial cellular processes including the
      maintenance of cell shape, motility and cell division. Actins from the most
      divergent sources still share amino-acid identities in excess of 70% (ref. 3).
      This may well explain why low-abundance homologues of actin have been difficult
      to isolate. Genes encoding distant relatives of actin in budding and fisson yeast
      have now been cloned. We report here the discovery of a vertebrate actin-like
      protein, which we name centractin. A full-length complementary DNA clone was
      isolated whose sequence reveals amino-acid identities with actin of over 50%,
      increasing to more than 70% when conservative amino-acid changes are considered.
      Northern analysis and western blotting indicate a ubiquitous tissue and species
      distribution. Morphological and biochemical criteria show that centractin is
      associated with centrosomes.

PMID- 1356231
TI  - Effects of the local application of 3-PPP and sulpiride enantiomers into the
      nucleus accumbens or into the ventral tegmental area on rat locomotor activity:
      evidence for the functional importance of somatodendritic autoreceptors.
AB  - The present series of experiments was performed in order to determine the
      relative role of presynaptic and somato-dendritic autoreceptors for the sedative
      effects produced by systemically administered dopaminergic agonists. Thus, the
      effects of intracerebral administration of 3-(3-hydroxyphenyl)-N-n
      propylpiperidine (3-PPP), or sulpiride, enantiomers on spontaneous locomotor
      activity was investigated in rats. It was found that the local application of (
      )3-PPP, but not (+)3-PPP, into the nucleus accumbens (1.25-80.0 micrograms,
      bilaterally) produced a suppression of the locomotor activity, whereas the local
      application of the two enantiomers into the ventral tegmental area resulted in a
      suppression of the locomotor activity in the same dose range. Thus, the full
      dopamine D2 agonist (+)3-PPP produced suppression of locomotor activity only
      after local application into the somato-dendritic region, suggesting that in
      terminal areas postsynaptic receptor stimulation effectively counterbalanced the
      functional consequences of presynaptic receptor stimulation. The sulpiride
      enantiomers both produced a suppression of locomotor activity after local
      application into the accumbens (0.2-5.0 micrograms, bilaterally). In the ventral
      tegmental area, however, (-)sulpiride administration (0.2-5.0 micrograms,
      bilaterally) resulted in an increased locomotion, whereas the (+)enantiomer
      produced no effect or, at the highest dose (5.0 micrograms), a suppression of the
      locomotor activity. These observations indicate that for a dopamine D2
      antagonist, the postsynaptic receptor blockade in the terminal region, resulting
      in behavioral suppression, not only counteract compensatory effects produced via
      the presynaptic receptor in this region, but also to a great extent overshadow
      the functional consequences of somatodendritic autoreceptor blockade.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1356232
TI  - Distinct pathways for beta-adrenoceptor-induced up-regulation of muscarinic
      acetylcholine receptors and inhibitory G-protein alpha-subunits in chicken
      cardiomyocytes.
AB  - Exposure of cardiomyocytes from chicken embryos for 3 days to the beta
      adrenoceptor agonist, isoproterenol, lead to a down-regulation of beta
      adrenoceptors by about 70% and to a decrease in isoproterenol-stimulated adenylyl
      cyclase activity by about 40% (homologous desensitization). In addition, the
      isoproterenol treatment induced an increase in the level of muscarinic
      acetylcholine receptors by about 30% and an increase in pertussis toxin-catalyzed
      ADP-ribosylation of two about 40 kDa proteins, most probably alpha-subunits of
      the inhibitory G-protein (Gi), by about a factor of two (heterologous
      desensitization). The purpose of the present study was to characterize the role
      of beta-adrenoceptor-dependent and -independent mechanisms in heterologous
      desensitization of adenylyl cyclase. Therefore, the effect of pretreatment with
      the beta-adrenoceptor antagonist, propranolol, with the partial agonists,
      celiprolol and xamoterol, and with the beta-adrenoceptor-independent adenylyl
      cyclase activators, prostaglandin E1 and forskolin, on beta-adrenoceptors,
      muscarinic acetylcholine receptors and pertussis-toxin-catalyzed ADP-ribosylation
      of G-protein alpha-subunits was studied. Pretreatment of the cardiomyocytes for 3
      days with xamoterol or celiprolol, but not with propranolol, induced a small
      decrease in beta-adrenoceptor number and in isoproterenol-stimulated adenylyl
      cyclase activity by about 15-20%. Exposure to prostaglandin E1 and forskolin lead
      to a more pronounced decrease in beta-adrenoceptor binding and in isoproterenol
      mediated adenylyl cyclase stimulation by about 40-60% (heterologous
      desensitization). An increase in the level of muscarinic acetylcholine receptors,
      similar to that induced by isoproterenol exposure, was only observed after
      pretreatment with the partial agonists, celiprolol and xamoterol, but not after
      pretreatment with the beta-adrenoceptor-independent agonists, prostaglandin E1
      and forskolin, nor after pretreatment with propranolol. In contrast,
      prostaglandin E1 and forskolin exposure lead to a similar increase in pertussis
      toxin-catalyzed ADP-ribosylation of about 40 kDa G-proteins as isoproterenol
      exposure whereas treatment with propranolol, celiprolol and xamoterol had no or
      only a very small effect on pertussis toxin substrates. In summary, the data
      suggest that, similar as shown for homologous desensitization, cyclic AMP
      dependent and -independent mechanisms are also involved in heterologous
      desensitization of adenylyl cyclase stimulation. The beta-adrenoceptor-induced
      upregulation of muscarinic acetylcholine receptors and of the alpha-subunits of
      pertussis toxin-sensitive G-proteins, most probably of Gi, seem to be mediated
      via distinct pathways.

PMID- 1356233
TI  - Systemic administration of baclofen and the GABAB antagonist, CGP 35348, does not
      affect GABA, glutamate or aspartate in microdialysates of the striatum of
      conscious rats.
AB  - Previous in vitro experiments have shown that the GABAB agonist, baclofen, and
      the antagonist, CGP 35348, respectively, decrease and increase the autoreceptor
      mediated release of GABA in brain slices and synaptosomes. Since it is not clear
      whether these autoreceptors are operative in vivo, an attempt was made to
      reproduce these results in brain dialysis experiments, knowing that only positive
      results would permit a conclusion in view of the doubts expressed in the
      literature with respect to the origin of extracellular GABA. Because of older
      reports of an inhibitory action of baclofen on the in vitro release of glutamate,
      which might be ascribed to the action of presynaptic GABAB heteroreceptors,
      extracellular glutamate and aspartate were also measured. Neither (-)-baclofen,
      administered systemically at a dose of 20 mg/kg i.p., nor the GABAB antagonist,
      CGP 35348 (300 mg/kg i.p.) had significant effects on basal overflow of GABA,
      glutamate, or aspartate nor on that evoked by 100 mmol/l K+ in the striatum of
      the conscious, freely moving rat. To ascertain this result, (-)-baclofen was also
      administered between two K+ stimulations, so that the first stimulation could
      serve as an intraindividual control of the second. The compound did not
      significantly affect K+ evoked overflow of any of the three transmitter amino
      acids under these conditions. It must be emphasized that these data do not
      exclude the operativity of presynaptic GABAB auto- and heteroreceptors in vivo.
      They only suggest that this question must, in all probability, be addressed by
      other techniques than brain dialysis.

PMID- 1356234
TI  - Effect of alpha 2-adrenoceptor agonists on the expression of morphine-withdrawal
      in rats.
AB  - Previous studies using clonidine indicate that alpha 2-adrenoceptors are involved
      in suppressing opiate-withdrawal symptoms. However, clonidine may act as a
      partial agonist at alpha 2-adrenoceptors and it also possesses significant alpha
      1-receptor agonist activity. The aim of this study was to determine the role of
      alpha 2-adrenoceptors in the expression of opiate withdrawal signs using morphine
      dependent rats. A range of agonists were selected for study on the basis of their
      differential preferences for alpha-adrenoceptors. Hooded Wistar rats were made
      physically dependent on morphine (s.c. injection of an emulsion releasing a total
      of 250 mg/kg of morphine base over 48 h). Test drugs were injected s.c. followed
      by naloxone (10 mg/kg i.p.) 20 min later. The incidence of 5 selected withdrawal
      signs was recorded during the following 20 min. The alpha 2-adrenoceptor agonists
      displayed different profiles of activity. Azepexole (1-10 mg/kg) reduced all
      signs. Clonidine (80-800 micrograms/kg) reduced all signs except paw shakes while
      guanfacine (25-250 micrograms/kg) reduced all except jumping and diarrhoea.
      Talipexole (0.1-1 mg/kg) reduced all signs except diarrhoea which was not
      affected and jumping which was markedly enhanced. UK 14,304 (80-800
      micrograms/kg) reduced jumps, potentiated paw shakes but did not affect body
      shakes, teeth chattering or diarrhoea. The results suggest that there are
      subpopulations of alpha 2-adrenoceptors that modulate the expression of opiate
      withdrawal signs and/or that some of the drugs used affect receptors other than
      alpha 2-adrenoceptors.

PMID- 1356235
TI  - Role of alpha 1A adrenoceptor subtype in production of the positive inotropic
      effect mediated via myocardial alpha 1 adrenoceptors in the rabbit papillary
      muscle: influence of selective alpha 1A subtype antagonists WB 4101 and 5
      methylurapidil.
AB  - In order to elucidate the contribution of alpha 1A subtype to the positive
      inotropic effect mediated by myocardial alpha 1 adrenoceptors, the influence of
      the alpha 1A selective antagonists WB 4101 and 5-methylurapidil on the alpha 1
      mediated positive inotropic effect (induced by phenylephrine in the presence of a
      beta adrenoceptor blocking agent bupranolol) was assessed in the isolated rabbit
      papillary muscle. WB 4101 (10(-9)-10(-7) mol/l) shifted the concentration
      response curve of the alpha 1-mediated positive inotropic effect to the right in
      parallel, but the slope of Schild plot did not meet the competitive antagonism:
      WB 4101 shifted the curve by log one unit at 10(-9) mol/l, whereas it did not
      cause further shift at higher concentrations of 10(-8) and 10(-7) mol/l. WB 4101
      did not affect the beta adrenoceptor-mediated positive inotropic effect. 5
      Methylurapidil (10(-9) to 10(-7) mol/l) shifted the curve of alpha 1-mediated
      positive inotropic effect to the right and downwards in a concentration-dependent
      manner; the slope of Schild plot calculated at the level of 20% of the maximum
      response to phenylephrine was close to unity. 5-Methylurapidil at 3 x 10(-7)
      mol/l abolished the alpha 1-mediated positive inotropic effect. In addition, 5
      methylurapidil inhibited the beta adrenoceptor-mediated positive inotropic effect
      in the same concentration range as it antagonized the alpha 1-mediated positive
      inotropic effect, indicating that 5-methylurapidil is not selective for
      myocardial alpha 1 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356236
TI  - Pharmacokinetic interaction between carbamazepine and neuroleptics after combined
      prolonged treatment in rats.
AB  - This study investigates how neuroleptics of phenothiazine or thioxanthene
      structure influence the pharmacokinetics of carbamazepine. Experiments were
      carried out on male Wistar rats. Carbamazepine and the neuroleptics were
      administered i.p., separately or together, for 2 weeks in the following daily
      doses (mg/kg): carbamazepine 15 during the 1st week of treatment and 20 during
      the 2nd week of treatment, promazine 10, chlorpromazine 2, perazine 10,
      chlorprothixene 2, flupenthixol 0.5. One hour after the last injection of
      carbamazepine and/or the neuroleptic, samples of blood plasma and brain were
      taken to determine the concentrations of carbamazepine and two of its
      metabolites: 10,11-epoxide and trans-10,11-diol. The neuroleptics increased the
      concentration of carbamazepine in plasma and in brain, but tended to decrease
      (with the exception of chlorpromazine) the concentration of the epoxide and
      increased the concentration of trans-10,11-diol. Metabolic in vitro studies did
      not show any significant differences between rats treated with carbamazepine
      alone and those treated with carbamazepine plus neuroleptic in the rates of the
      carbamazepine epoxidation, of 10,11-epoxide hydrolysis or of 1-naphthol
      glucuronidation.

PMID- 1356237
TI  - Pertussis toxin abolishes the inhibition of Ca2+ currents and of noradrenaline
      release via alpha 2-adrenoceptors in chick sympathetic neurons.
AB  - Effects of alpha 2-adrenoceptor agonists on whole-cell Ca2+ currents and 3H
      noradrenaline release were investigated by applying the patch-clamp technique and
      electrical field stimulation to cultured embryonic chick sympathetic neurons. A
      24-h exposure of the sympathetic neurons to pertussis toxin (100 ng/ml) abolished
      both the alpha 2-adrenoceptor-mediated inhibition of Ca2+ currents and the
      modulation of noradrenaline release caused by noradrenaline (1 mumol/l; in the
      presence of 10 mumol/l cocaine) or the alpha 2-adrenoceptor agonists 5-bromo-6-(2
      imidazolin-2- ylamino)quinoxaline (UK 14,304, 10 mumol/l) and clonidine (10
      mumol/l). These results suggest that the alpha 2-autoreceptor-mediated inhibition
      of noradrenaline release from chick sympathetic neurons operates through the
      modulation of Ca2+ channels via pertussis-toxin-sensitive GTP-binding-proteins.

PMID- 1356238
TI  - Adaptation of mouse leukemia cells L1210 to vincristine. Evidence for expression
      of P-glycoprotein.
AB  - A vincristine resistant cell line was obtained from mouse leukemia cells L1210 by
      long-term adaptation in a medium with stepwise increasing concentrations of
      vincristine. By Western blotting using monoclonal antibody C219, positive signal
      on the presence of P-glycoprotein was observed in the resistant cells. Moreover,
      hybridization of mRNA from vincristine resistant cells with radiolabeled MDR1
      cDNA probe gave evidence about the expression of MDR1 gene. The observed
      resistance may be depressed by application of "chemosensitizers" such as (1)
      calcium entry blockers (verapamil and nifedipine); (2) neuroleptics
      (trifluorperasine) and (3) local anesthetics (lidocaine) directly to the grow
      medium. Any significant effect in O2 consumption as well as incorporation of [U
      14C]-glucose by the sensitive or resistant cells was not detected in the absence
      of vincristine. Presence of vincristine induced increasing velocity of O2
      consumption by resistant cells from 2.5 +/- 0.3 to 3.3 +/- 0.2
      microliters/min.10(6) cells, and, on the other hand, decreasing O2 consumption by
      sensitive cells from 2.3 +/- 0.2 to 1.7 +/- 0.1 ml/min.10(6) cells. The presence
      of vincristine induced less potent decrease in glucose incorporation by resistant
      cells in comparison with values which were observed in sensitive cells.

PMID- 1356239
TI  - Hypertension after hemorrhagic fever with renal syndrome.

PMID- 1356240
TI  - Effect of chronic renal failure with and without secondary hyperparathyroidism on
      the activities of synaptosomal tyrosine hydroxylase and monoamine oxidase.
AB  - Norepinephrine (NE) content, release and uptake by brain synaptosomes are reduced
      in chronic renal failure (CRF), and this has been attributed to the state of
      secondary hyperparathyroidism. The decrease in NE content in CRF could not be
      explained by changes in NE uptake or release since in normal circumstances, NE
      content usually remains unchanged despite fluctuation in NE uptake and release.
      Since NE content is determined by its production and degradation, we examined the
      effect of CRF with and without excess parathyroid hormone (PTH) on the Michaelis
      Menton constant (Km) and Vmax of tyrosine hydroxylase (TH), the rate-limiting
      enzyme for NE production, and monoamine oxidase (MAO), an enzyme involved in NE
      degradation of brain synaptosomes. Brain synaptosomes from rats with a 21-day CRF
      have a significantly (p less than 0.01) lower Vmax of TH (39.5 +/- 5.3 pmol
      tritiated H2O/mg protein/min) than that of normal rats (61. +/- 7.5 pmol
      tritiated H2O/mg protein/min) and a higher Km of MAO (59 +/- 2.9 nM tyramine)
      than normal animals (46 +/- 1.7 nM tyramine). Parathyroidectomy (PTX) in CRF rats
      normalized Vmax of TH (54 +/- 4.5 pmol tritiated H2O/mg protein) and Km of MAO
      (48.4 +/- 2.3 nM tyramine). Cytosolic calcium, [Ca2+]i, in brain synaptosomes is
      significantly (p less than 0.01) higher in rats with CRF (488 +/- 8.5 nM) than in
      normal (355 +/- 6.0 nM) or PTX-CRF (360 +/- 8.1 nM) rats.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1356241
TI  - Regulation of nucleus accumbens dopamine release by the dorsal raphe nucleus in
      the rat.
AB  - The effects of microinfusing L-glutamate, serotonin (5-HT), (+-)-8-hydroxy-2-(di
      N-propylamino) tetralin (8-OH DPAT; a 5-HT1A agonist), and muscimol (a GABAA
      agonist) into the dorsal raphe nucleus on the extracellular levels of 5-HT,
      dopamine (DA) and their metabolites in the nucleus accumbens were studied in
      unanesthetized, freely moving, adult male Wistar rats, using the technique of
      microdialysis coupled with small-bore HPLC. Administration of 0.75 micrograms L
      glutamate produced a 25-50% increase (P less than 0.05) in the extracellular
      levels of both 5-HT and DA. On the other hand, infusion of 8-OH DPAT and, to a
      lesser extent, 5-HT produced a significant (P less than 0.05) decrease in the
      extracellular levels of both 5-HT and DA. Muscimol (0.25 or 0.50 microgram) had
      little effect on the extracellular concentrations of 5-HT or DA following its
      administration. In general, the extracellular levels of the major metabolites of
      5-HT and DA in the nucleus accumbens were not altered by microinfusion of any of
      the agents. The data indicate that (a) the 5-HT neurons projecting to the nucleus
      accumbens from the dorsal raphe nucleus can be activated by excitatory amino acid
      receptors and inhibited by stimulation of 5-HT1A autoreceptors, and (b) the
      dorsal raphe nucleus 5-HT neuronal system may regulate the ventral tegmental area
      DA projection to the nucleus accumbens.

PMID- 1356242
TI  - Competitive NMDA receptor antagonists raise electrically kindled generalized
      seizure thresholds.
AB  - A sensitive method of estimation of generalized seizure thresholds (GSTs) was
      used to estimate the relative anticonvulsant potencies of four competitive NMDA
      antagonists against fully amygdala-kindled seizures. All of the antagonists
      tested showed potent, dose-dependent anticonvulsant activity following focal
      administration at doses causing no, or only minimal, overt behavioural
      abnormalities. These doses were similar to those which have previously been shown
      to inhibit the development of the kindling process i.e. which show
      antiepileptogenic activity. Two novel, competitive NMDA antagonists, CGP 37849
      and CGP 39551, both unsaturated analogues of the NMDA antagonist AP5, showed by
      far the greatest anticonvulsant potencies (211-fold and 33-fold greater activity
      than the parent molecule, respectively). Recent reports of oral anticonvulsant
      activity of these two compounds in both rodent and primate models of epilepsy
      (12, 13) make them leading candidates for clinical testing as novel antiepileptic
      agents in man. Previous reports of weak or non-existent anticonvulsant activity
      of competitive NMDA antagonists in the kindling model of epilepsy most likely
      result from the use of experimental protocols which are inherently insensitive in
      detecting drug-induced changes in seizure thresholds.

PMID- 1356243
TI  - Comparison of alterations in tyrosine hydroxylase, dopamine levels, and dopamine
      uptake in the striatum of the weaver mutant mouse.
AB  - Previous reports have shown that among the markers for the nigro-striatal
      dopamine (DA) system measured in the striatum, dopamine uptake seems to be more
      severely affected than the others in the weaver mutant mouse. In the present
      study we examined DA levels, tyrosine hydroxylase (TH) activity, and high
      affinity DA uptake to determine if the DA uptake is most affected when all the
      measurements are made in the same striatal homogenate in the same laboratory. We
      found that the DA uptake activity was most altered (93% lower) compared to DA
      levels (68% lower) and TH activity (64% lower). The DA uptake was so low in the
      weaver that we could not obtain reliable kinetic parameters. For TH activity we
      found that the Vmax was 36% lower while the Km for L-tyrosine was 92% higher in
      the weaver striatum. This lower affinity for substrate suggests that the TH
      enzyme itself may be altered in the nigro-striatal system of the weaver mutant
      mouse.

PMID- 1356244
TI  - The ontogeny of the uptake systems for glutamate, GABA, and glycine in synaptic
      vesicles isolated from rat brain.
AB  - The ontogeny of the uptake of glutamate, GABA and glycine into synaptic vesicles
      isolated from rat brain has been investigated. The vesicular uptake of the three
      amino acids increased with developmental age in parallel with synaptogenesis,
      indicating a functional role of uptake of the amino acids by synaptic vesicles in
      the nerve terminals. Uptake of the amino acids by plasma membrane particles
      (synaptosomes) in brain homogenate showed a somewhat different developmental
      profile. The uptake of glutamate increased markedly with developmental time,
      while the uptake of GABA showed only a slight increase. Uptake of glycine by
      plasma membrane particles was very low and therefore not registered. The observed
      developmental increase in uptake of glycine by synaptic vesicles isolated from
      brain, supports previous reports indicating that glycine can be taken up by
      vesicles from non-glycine terminals.

PMID- 1356245
TI  - Levels, uptake, and release of glycine and glutamate in the rat pontine reticular
      formation.
AB  - In this work we have determined the levels of glycine, glutamate, and other amino
      acids in the rat pontine reticular formation (PRF), in addition to some
      properties of the uptake and release of labeled glycine and glutamate in slices
      of this region. Glutamate was the most concentrated amino acid in the PRF,
      although its content was about half that of the striatum. Surprisingly, glycine
      levels in the PRF were 3.2-fold higher than in the striatum, whereas GABA content
      was similar in both regions. The uptake of both glycine and glutamate by PRF
      slices was strictly Na(+)-dependent. Their release was stimulated by K(+)
      depolarization, but only the release of glycine was Ca(2+)-dependent. These
      findings suggest that glycine is a strong candidate for a neurotransmitter role
      in the PRF and that glutamate might also play such a role in this region.

PMID- 1356246
TI  - Neurochemical changes associated with the action of acute administration of
      diazepam in reversing the behavioral paradigm conditioned emotional response
      (CER).
AB  - Neurotransmitter turnover of biogenic monoamines (dopamine, norepinephrine, and
      serotonin) and amino acids (glutamate, aspartate, and gamma-aminobutyric acid)
      was evaluated in rats exposed to the conditioned emotional response (CER)
      paradigm in the absence (total suppression) or presence of acute 5 mg/kg i.p.
      diazepam (which reversed suppression and restored normal responding). Based on
      previous studies of CER, with controls for shock and stimulus histories, the
      results with respect to the anxiolytic could be divided into several categories:
      changes in turnover which are associated only with the CER behavior; changes
      associated only with the drug, diazepam; changes which augmented the effects of
      the behavior; or changes which were the reverse of those associated with the
      behavior. Due to the multitude and complexity of the results, not all
      observations have clear explanations at this time. However, for the CER behavior
      per se, it is apparent that a combination of neurotransmitters, including some
      implications about acetylcholine, act in concert to bring about the behavioral
      suppression. The action of diazepam is more complex, involving the full spectrum
      of neurotransmitters to bring about its direct and indirect effects.

PMID- 1356247
TI  - [Droperidol in the treatment of hiccup of central origin].
AB  - Persistent intractable hiccup (over 24 hours) was observed in four patients.
      Administration of 2.5 mg droperidol intravenously stopped the hiccup for some
      hours (4-12). This dose was repeated every 4-12 hours for some days. The hiccup
      stopped completely.

PMID- 1356249
TI  - Protection from kainic acid neuropathological syndrome by NMDA receptor
      antagonists: effect of MK-801 and CGP 39551 on neurotransmitter and glial
      markers.
AB  - Systemic administration of kainic acid results in the development of a
      characteristic convulsive syndrome, accompanied by neuropathological alterations
      and loss of transmitter markers in some forebrain regions. Since some of these
      effects appear to involve the N-methyl-D-aspartate (NMDA) subtype of excitatory
      amino acid receptors, the protection given by a non-competitive (MK-801) and a
      competitive (CGP 39551) NMDA receptor antagonist against the loss of
      glutamatergic and gamma-amino butyric acid (GABAergic) neurochemical markers was
      compared. Appropriate doses of both compounds (1 mg/kg MK-801 and 25 mg/kg CGP
      39551) completely reversed the decrease of high affinity uptake of glutamate and
      activity of glutamate decarboxylase in the olfactory cortex, amygdala,
      hippocampus and lateral septum. In addition, they also essentially counteracted
      the increase of a glial marker, the enzyme glutamine synthetase, consequent to
      neuronal degeneration. The results confirmed that involvement of NMDA receptors
      is essential for the full expression of neuropathological effects of kainic acid.
      They also support the use of a competitive antagonist of the NMDA receptor, such
      as CGP 39551, to afford substantial protection against the excitotoxic damage,
      whilst giving fewer side effects and motor disturbances than MK-801.

PMID- 1356248
TI  - The effects of pertussis toxin on dopamine D2 and serotonin 5-HT1A autoreceptor
      mediated inhibition of neurotransmitter synthesis: relationship to receptor
      reserve.
AB  - Irreversible inactivation of striatal D2 dopamine (DA) autoreceptors with N
      ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) or inactivation of striatal
      guanine nucleotide binding proteins (G proteins) with pertussis toxin (PT)
      shifted the dose-response curve for N-n-propylnorapomorphine (NPA)-mediated
      inhibition of gamma-butyrolactone (GBL)-induced elevation of L-3,4
      dihydroxyphenylalanine (L-DOPA) to the right, with a decrease in the maximum
      response. For the partial agonist (+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine
      [(+)-3-PPP], in contrast, there was little shift in the ED50, after inactivation
      of either D2 receptors or G proteins. Completely analogous effects were found at
      the somatodendritic 5-HT1A autoreceptor in the raphe nuclei, mediating inhibition
      of the synthesis of serotonin (5-HT); the full agonist, 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) and the partial agonist, buspirone were utilized
      to inhibit the synthesis of 5-HT, as measured by changes in levels of L-5
      hydroxytryptophan (5-HTP). Additionally, in both systems, combined treatment with
      pertussis toxin, followed by EEDQ, reduced the maximum effect, when compared to
      either agent alone but had little further effect on the ED50. In systems
      exhibiting a large receptor reserve for agonists, such as those described above,
      the same pattern of response seen after inactivation of receptors or G proteins
      may reflect the operation of a common mechanism underlying the phenomenon of
      receptor reserve.

PMID- 1356250
TI  - Injection of the competitive NMDA receptor antagonist AP-5 into the nucleus
      accumbens of monoamine-depleted mice induces pronounced locomotor stimulation.
AB  - Following injection of 5 micrograms of the competitive NMDA receptor antagonist
      AP-5 into the nucleus accumbens of monoamine-depleted mice a pronounced locomotor
      stimulation was produced. Additional treatment with an intraperitoneal (i.p.)
      injection of the alpha-adrenoceptor agonist clonidine markedly increased the
      locomotor effects of AP-5 administration into the nucleus accumbens. Injection of
      5 or 10 micrograms AP-5 into the dorsal striatum was ineffective with regard to
      locomotor stimulation. However, when AP-5 (10 micrograms) was combined with an
      i.p. injection of clonidine, a marked locomotor stimulation was produced
      following application into the dorsal striatum, but not following application
      into the prefrontal cortex. The present results are in line with the idea that
      corticostriatal glutamatergic pathways, especially those projecting to the
      ventral striatum, exert an inhibitory influence on psychomotor functions.

PMID- 1356251
TI  - Effects of acute administration of the 5-HT3 receptor antagonist, BRL 46470A, on
      the behaviour of mice in a two compartment light-dark box and during social
      interactions in their home cage and an unfamiliar neutral cage.
AB  - Adult male CD1 mice received the 5-HT3 receptor antagonist, BRL 46470A, by
      intraperitoneal injection at three dose levels (2.5 mg/kg, 25 and 2.5
      micrograms/kg). Controls were injected with physiological saline. At 30 min after
      injection, the behaviour of each mouse was examined by ethological procedures,
      when encountering an untreated partner for 5 min in its home cage and for 5 min
      in the more aversive situation of an unfamiliar neutral cage. The behaviour of
      each mouse also was monitored for 5 min in a two compartment light-dark box. At
      all doses tested, BRL 46470A increased the time spent in the light compartment of
      the light-dark box. At the smallest dose (2.5 micrograms/kg), the number of
      transitions between light and dark compartments was increased and there also was
      an increase (per unit time) in the numbers of squares crossed and number of scans
      in the light compartment. At all doses tested, BRL 46470A increased social
      investigation and reduced non-social exploratory activity in both the home cage
      and the unfamiliar neutral cage. In both test situations, increase of social
      investigation was maximum at 25 micrograms/kg, and at this dose, aggressive
      behaviour was also enhanced. In the neutral cage, digging in the sawdust by drug
      treated mice showed a progressive dose-related increase. These results indicate
      potent anxiolytic-like activity by BRL 46470A and also demonstrate increased
      reactivity to unfamiliar environmental stimuli, such as novel sawdust. The
      significance of these findings is discussed.

PMID- 1356253
TI  - Evidence for differential opioid mu 1- and mu 2-receptor-mediated regulation of
      heart rate in the conscious rat.
AB  - The possibility that mu-opioid-induced tachycardia and bradycardia could be
      mediated by different subtypes of the mu-receptor was studied in conscious
      Sprague-Dawley rats. The selective mu-receptor agonist dermorphin and its analog,
      TAPS (Tyr-D-Arg-Phe-sarcosine), a putative mu 1-receptor agonist, were given
      centrally. Tyr-D-Arg-Phe-sarcosine increased the heart rate, the response being
      inversely correlated to the dose (an increase of 71 +/- 22, 49 +/- 14 and 30 +/-
      17 beats/min at doses of 0.3, 3 and 30 pmol, respectively). Dermorphin induced
      less clear changes in heart rate (maximum increase of 39 +/- 14 beats/min at the
      dose of 1 pmol). After treatment with the mu 1-selective antagonist naloxonazine
      (NAZ), TAPS 30 pmol and dermorphin 1 pmol decreased heart rate by -22 +/- 10 and 
      24 +/- 7 bpm, respectively. The bradycardiac effect of larger doses of dermorphin
      was potentiated by NAZ (from -25 +/- 8 to -97 +/- 22 bpm) but abolished by the
      non-selective antagonist naloxone. These data suggest that the high affinity mu 1
      opioid receptors mediate tachycardic responses and mu 2-receptors mediate
      bradycardic responses.

PMID- 1356252
TI  - Endogenous opioids may be involved in idazoxan-induced food intake.
AB  - In this study it has been shown that the unexpected increase in food consumption,
      produced by the alpha 2-adrenoceptor antagonist idazoxan (10 mg/kg, i.p.) in
      rats, was significantly attenuated by small doses of the opioid antagonist (-)
      naloxone (0.1, 1 mg/kg, i.p.) and totally inhibited by a small dose of naltrexone
      (1 mg/kg, i.p.). On the other hand, idazoxan-induced feeding was not affected by
      (+)-naloxone (0.1, 1 mg/kg, i.p.), which is inactive at opioid receptors. In
      addition, idazoxan-induced food consumption was not blocked by the delta-opioid
      antagonist, naltrindole (0.1, 1 mg/kg, i.p.) nor by the mu/delta-antagonist,
      RX8008M (16-methyl cyprenorphine; 0.1, 1 mg/kg, i.p.), which clearly
      discriminates between mu/delta- and kappa-opioid receptor function in vivo. These
      findings suggest that idazoxan may lead to the release of endogenous opioid
      peptides, which subsequently stimulate feeding by activation of kappa-, as
      opposed to mu- or delta-opioid receptors. This response is unlikely to be due to
      alpha 2-adrenoceptor blockade, since other highly selective alpha 2-adrenoceptor
      antagonists do not increase food intake and, instead may reflect the high
      affinity of idazoxan for non-adrenoceptor idazoxan binding sites.

PMID- 1356254
TI  - Effects of somatostatin and anti-somatostatin serum on picrotoxin-kindled
      seizures.
AB  - The effects of somatostatin, administered into different areas of the brain were
      studied in preliminary picrotoxin-kindled rats. The injection of somatostatin
      into the lateral ventrical of the brain (i.c.v.) (1.8 nmol), the hippocampus (0.6
      nmol) or the amygdala (0.6 nmol), resulted in a decrease in the severity of the
      picrotoxin-induced convulsions. Application of the peptide into the caudate
      putamen or the substantia nigra reticulata did not alter the behavioural
      manifestations of the kindled seizures. The local injection of anti-somatostatin
      serum (1:5) into the hippocampus increased the severity of the kindled
      convulsions and blocked the anticonvulsive effect of somatostatin, given
      intraventricularly. Local administration of anti-somatostatin serum into the
      amygdala did not alter the kindled seizures and did not abolish the
      anticonvulsive action of somatostatin given intraventricularly. It is concluded
      that somatostatin could take part in endogenous control of seizures through a
      suppressant influence on limbic structures; the hippocampus could be a specific
      site for the antiepileptic action of somatostatin.

PMID- 1356257
TI  - Abstracts of the Norwegian Virology Symposium IV. Ustaoset, March 19-20, 1992.

PMID- 1356255
TI  - Estradiol plus progesterone promote glutamate-induced release of gamma
      aminobutyric acid from preoptic area synaptosomes.
AB  - Treatment of ovariectomized rats with both estradiol and progesterone in vivo
      resulted in a marked enhancement of glutamate-induced release of newly
      synthesized [3H]gamma-aminobutyric acid (GABA) from synaptosomes of the preoptic
      area in vitro. With this treatment, as little as 0.01 nM glutamate, in vitro,
      enhanced release of GABA. In contrast, glutamate, in vitro, did not stimulate
      release of GABA from synaptosomes, obtained from rats treated with either
      estradiol or progesterone alone and only large concentrations of glutamate (1.0
      and 10 mM) caused a modest release of GABA from synaptosomes from ovariectomized,
      vehicle-treated rats. Also, treatment with estradiol plus progesterone did not
      alter glutamate-induced release or exchange of [3H]glutamate. Glutamate-induced
      release of GABA was calcium-independent and attenuated by the putative chloride
      channel antagonist, 4,4'-diisothiocyanatostilbene-2,2'-DL-disulfonic acid. Thus,
      glutamate-induced, steroid-enhanced release of GABA may occur through a chloride
      dependent carrier rather than by exocytosis. In addition to enhancement by
      glutamate, release of GABA was also enhanced by D-aspartate, an agent that is
      transported by the neuronal glutamate carrier. It is postulated that enhancement
      of glutamate-induced release of GABA, by estradiol plus progesterone in the
      preoptic area, represents one process by which these steroids modulate
      reproductive function in female rats.

PMID- 1356256
TI  - Activity of two primary human metabolites of nomifensine on stimulated efflux and
      uptake of dopamine in the striatum: in vitro voltammetric data in slices of rat
      brain.
AB  - Several antidepressant drugs have active metabolites. This study sought to
      establish whether two of the main human metabolites of nomifensine (M2: 8-amino-2
      methyl-4-(3-methoxy-4-hydroxyphenyl)-1,2,3,4- tetrahydroisoquinoline and M3: 8
      amino-2-methyl-4-(3-hydroxy-4-methoxyphenyl)-1,2,3,4- tetrahydroisoquinoline) had
      actions on the release and uptake of dopamine (DA). Experiments were conducted in
      superfused striatal slices of the rat. The efflux of DA was evoked by single
      constant-current pulses (0.1 msec, 10 mA) and trains (20 pulses, 50 Hz), applied
      alternately every 10 min and monitored using fast cyclic voltammetry at carbon
      fibre microelectrodes. Nomifensine (5 x 10(-7) M) significantly increased the
      efflux of DA on both single pulse (302% of pre-drug) and train stimuli (529%) and
      increased the uptake half-life (178% of pre-drug). The M2 metabolite had similar
      potency on the efflux of DA (260%: pulse, 570%: train) but without any effect on
      uptake of DA. Nomifensine and M2 increased efflux of DA more on trains than on
      single pulses. The M3 metabolite (5 x 10(-7) M) increased efflux of DA only
      moderately. The selective blocker of the uptake of DA, GBR 12909 (3 x 10(-7) M),
      increased efflux of DA on single pulse (430%) and train stimuli (645%) and
      blocked uptake of DA (t1/2: 292%). Amfonelic acid, the psychomotor stimulant (10(
      7) M) blocked uptake of DA (t1/2: 234%) and elevated efflux of DA to a greater
      extent on trains (1007%) than on single pulses (495%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1356258
TI  - Protective effect of epidermal growth factor on glutamate neurotoxicity in
      cultured cerebellar neurons.
AB  - The effects of epidermal growth factor (EGF) on glutamate-induced neuronal death
      were investigated in primary cultures of dissociated cerebellar neurons from
      fetal rats. Addition of an excess concentration of L-glutamate (5 mM) to the
      culture medium greatly decreased the number of surviving neurons 24 h later. When
      EGF was added to the culture medium 20 h prior to exposure to glutamate,
      glutamate-induced neuronal death was significantly reduced. The protective
      effects of EGF on glutamate neurotoxicity were concentration-dependent in the
      range of 0.01-10 ng/ml. When EGF was added 1 h prior to exposure to glutamate, it
      did not prevent glutamate-induced neuronal death, indicating that a longer
      exposure period is required for EGF to exert its protective effects. Furthermore,
      the protective effects of EGF on glutamate neurotoxicity disappeared in the
      presence of cycloheximide (0.1 microM), a protein synthesis inhibitor. These
      results suggest that EGF can protect brain neurons against glutamate toxicity
      through some protein synthesis.

PMID- 1356259
TI  - Correlation of c-erbB-2 protein expression and lymph node status in early gastric
      cancer.
AB  - For the prediction of nodal status of early gastric cancer, sections of formalin
      fixed, paraffin-embedded tissue from 220 early gastric cancers were analyzed
      immunohistochemically, using a polyclonal antibody against erbB-2 protein. The
      data of erbB-2 protein expression have been correlated with pathologic data, and
      a logistic regression analysis was made for the estimation of the significant
      factors responsible for lymph node metastasis. A pattern consistent with cell
      membrane staining was regarded as most specific for the erbB-2 expression. There
      were 22 (10%) cancers with evidence of erbB-2 protein expression. Positive
      staining was associated with only lymph node metastasis. The risk of lymph node
      metastasis was 3-fold greater in tumors having erbB-2 protein expression than in
      tumors without the expression. When the erbB-2 tissue status and
      clinicopathological parameters were entered into the logistic regression
      analysis, erbB-2 protein expression emerged as one of the independent significant
      factors for lymph node metastasis. These results indicate that early gastric
      cancer with erbB-2 protein expression may represent a potential risk of lymph
      node metastasis.

PMID- 1356260
TI  - Immunohistochemical detection of P glycoprotein, glutathione S transferase and
      DNA topoisomerase II in human tumors.
AB  - The expression of the drug resistance markers P glycoprotein (P-170), glutathione
      S transferase-pi (GST-pi) and DNA topoisomerase II (Topo II) was analyzed in 16
      human kidney carcinoma cell lines, 18 hematological malignancies, and 14 human
      breast carcinomas. We found a tendency for coexpression of increased P-170 and
      GST-pi and of increased P-170 and decreased Topo II expression in kidney
      carcinoma cell lines. A similar tendency was found between P-170 and GST-pi
      expression in breast carcinomas. In contrast, hematological malignancies did not
      show such a coexpression of resistance markers. Furthermore, we found
      interrelationships between the expression of resistance markers, resistance to
      doxorubicin or vincristine, and doubling times of kidney carcinoma cell lines.
      This indicates that the proliferative activity of tumor cells plays a role for
      the expression of resistance markers and the development of resistance to
      cytostatic drugs.

PMID- 1356261
TI  - Potentiation of lymphocyte proliferative responses by nickel sulfide.
AB  - Crystalline nickel sulfide (NiS) induced a spleen cell proliferation that
      resembles a mixed lymphocyte reaction (MLR). It depended on cell-cell
      interaction, induced high levels of interleukin-1 (IL-1) and interleukin-2 (IL-2)
      and the responding cell subpopulation was composed of CD4+ T lymphocytes.
      Furthermore, the proliferation was inhibited in a dose-dependent manner by
      magnesium. Crystalline NiS also increased significantly the spleen cell
      proliferative response to concanavalin A (Con A) and lipopolysaccharide (LPS)
      with magnesium potentiating the combined effects of crystalline NiS and mitogens.
      Interestingly, crystalline NiS did not show any effect on the induction of IL-2
      by Con A. The results described herein suggest that crystalline NiS can
      potentiate both antigenic (MLR) and mitogenic (Con A and LPS) proliferative
      responses in vitro. Crystalline NiS appears to potentiate these responses by
      acting in the form of ionic nickel on several intracellular targets for which
      magnesium ions have different noncompetitive interactions. The effects of
      magnesium on the potentiating action of crystalline NiS are different depending
      upon the type of primary stimulatory signal for proliferation (mitogenic or
      antigenic).

PMID- 1356262
TI  - CD45RA and CD45RO positive CD4 cells in human peripheral blood and periodontal
      disease tissue before and after stimulation with periodontopathic bacteria.
AB  - Flow cytometric analysis was used to examine naive and primed or memory CD4 cells
      extracted from periodontal lesions compared with cells from peripheral blood of
      healthy subjects before and after stimulation with the periodontopathic bacteria,
      Porphyromonas gingivalis and Fusobacterium nucleatum. In peripheral blood,
      approximately 60% and 40% of CD4 cells were CD45RO+ and CD45RA+ respectively at
      day 0. Phytohaemagglutinin (PHA) induced CD45RO expression on almost 100% of CD4
      cells. However, P. gingivalis and F. nucleatum stimulation did not cause any
      significant change in percentage of CD45RO+ CD4 cells except for a loss of
      antigen at day 6 together with re-expression at day 7, which also occurred on
      cells cultured in medium only. CD45RA expression on PHA and bacterial-stimulated
      peripheral blood CD4 cells remained fairly stable for the 10-d culture period.
      Greater than 90% CD4 cells extracted from healthy or marginal gingivitis (H/MG)
      and adult periodontitis (AP) lesions were CD45RO+ and this was maintained on AP
      cells throughout the 6-d culture period, except for a small decrease in the
      percentage of positive cells induced by P. gingivalis at day 3. Approximately 9%
      CD4 cells from H/MG tissue were CD45RA+, but about 22% AP cells expressed this
      antigen, and this increased again in P. gingivalis- and F. nucleatum-stimulated
      cultures after 3 d. Therefore, in peripheral blood P. gingivalis and F. nucleatum
      do not act as nonspecific T-cell mitogens and, in AP cells, these bacteria induce
      changes in phenotype, supporting previous data that although they may be
      polyclonal B-cell activators, they activate antigen specific T-cells.

PMID- 1356263
TI  - Slow inward current in single cells isolated from adult human ventricles.
AB  - Characteristics of the slow inward current (Isi) in human ventricular myocytes
      isolated from septal specimens obtained in patients undergoing corrective cardiac
      surgery were studied using the whole-cell clamp method. A first series of
      experiments was performed under normal standard superfusion. Clamping from -60 mV
      evoked an inward current with a threshold at about -35 mV, a maximum around +10
      mV and an apparent reversal potential at about +55 mV. No overlapping transient
      or background outward currents were detected in the -60 to +30 mV potential
      range, but time-dependent and steady-state outward currents were elicited at
      potentials above +30 mV. An overlap of steady-state activation and inactivation
      curves was present between -30 and +10 mV and a slight relief from inactivation
      was observed for voltages positive to +10 mV. The time course of inactivation
      consisted of fast and slow phases with time constants differing by a factor of
      eight. Slow time constants of inactivation were shorter at potentials that
      elicited larger Isi, and longer at potentials inducing smaller Isi. Recovery from
      inactivation evolved slowly with 100% reactivation occurring in about 4000 ms.
      Switching the holding potential from -60 to -40 mV led to a reversible decline of
      Isi without any change of the decay time constants. Isi was significantly
      increased by 0.1 microM isoproterenol. Total or partial inhibition by inorganic
      (2 mM Mn2+, 3 mM Co2+, 1 mM Cd2+) and organic (1 microM methoxyverapamil, 5
      microM diltiazem) calcium antagonists did not unmask any transient outward
      current. However, a consistent increase of Isi was reversibly observed with 3 mM
      4-aminopyridine while using standard solutions. A second series of experiments
      carried out with K(+)- and Na(+)-free solutions did not demonstrate any
      significant change from data observed with standard solutions except a reduction
      of outward currents at steps above +30 mV and alteration of inactivation
      kinetics. In this experimental setting, 4-aminopyridine also increased Isi but to
      a lesser degree. We conclude that Isi, as compared to the outward currents, is
      dominant in the diseased human ventricular cells we have studied.

PMID- 1356264
TI  - Partial purification and reconstitution of the human multidrug-resistance pump:
      characterization of the drug-stimulatable ATP hydrolysis.
AB  - Multidrug-resistant human tumor cells overexpress the MDR1 gene product P
      glycoprotein, which is believed to function as an ATP-dependent efflux pump. In
      this study we demonstrate that the partially purified P-glycoprotein, when
      reconstituted in an artificial membrane, catalyzes drug-stimulated ATP
      hydrolysis. Plasma membrane proteins of a human multidrug-resistant cell line, KB
      V1, were solubilized with 1.4% (wt/vol) octyl beta-D-glucopyranoside in the
      presence of 0.4% phospholipid and 20% (vol/vol) glycerol, and the crude detergent
      extract was chromatographed on DEAE-Sepharose CL-6B. The 0.1 M NaCl fraction,
      enriched in P-glycoprotein but devoid of Na,K-ATPase, was reconstituted by the
      detergent-dilution method. P-glycoprotein constituted 25-30% of the reconstituted
      protein in proteoliposomes. ATP hydrolysis by proteoliposomes was stimulated 3.5
      fold by the addition of vinblastine but was unaffected by the hydrophobic
      antitumor agent camptothecin, which is not transported by P-glycoprotein. The
      stimulatory effect of vinblastine was observed only if the protein was
      reconstituted in proteoliposomes, suggesting that either the substrate binding
      site(s) was masked by detergent or that the conformation of the soluble P
      glycoprotein might not be suitable for substrate-induced activation. Several
      other drugs that are known to be transported by P-glycoprotein enhanced the
      ATPase activity in a dose-dependent manner with relative potencies as follows:
      doxorubicin = vinblastine greater than daunomycin greater than actinomycin D
      greater than verapamil greater than colchicine. The basal and vinblastine
      stimulated ATPase activities were inhibited by vanadate (50% inhibition observed
      at 7-10 microM) but were not affected by agents that inhibit other ATPases and
      phosphatases. These data indicate that the P-glycoprotein, similar to other ion
      transporting ATPases, exhibits a high level of ATP hydrolysis (5-12 mumol per min
      per mg of protein).

PMID- 1356265
TI  - N-methyl-D-aspartate receptors are transiently expressed in the developing spinal
      cord ventral horn.
AB  - Quantitative receptor autoradiography was used to map the distribution of N
      methyl-D-aspartate (NMDA) receptors in the developing rat spinal cord. Three
      different specific ligands, which label partially overlapping subpopulations of
      NMDA receptors, were used: an agonist (L-[3H]glutamate), a noncompetitive
      antagonist ([3H]MK-801), and a competitive antagonist ([3H]CGP-39653). In the
      adult, NMDA receptors labeled with all three ligands are restricted to the
      substantia gelatinosa in the spinal dorsal horn. In marked distinction, at
      postnatal day 7 NMDA receptors labeled with L-[3H]glutamate and [3H]MK-801 are
      present throughout the spinal gray matter. NMDA receptors in the neonatal spinal
      ventral horn have a higher affinity for L-[3H]glutamate than those in the adult
      substantia gelatinosa. Over the second and third postnatal weeks, NMDA receptors
      are lost from all areas of the spinal gray matter except for the substantia
      gelatinosa. Neonatal NMDA receptors identified with [3H]CGP-39653 are restricted
      to the substantia gelatinosa. These results show that the immature ventral horn
      contains a subpopulation of NMDA receptors and raise the possibility that motor
      neurons transiently express NMDA receptors in early postnatal life. Ventral horn
      NMDA receptors may be a component of the mechanisms by which the mature phenotype
      of motor neurons is acquired through activity-dependent processes. The loss of
      NMDA receptors over the course of development may play a role in limiting the
      period of motor neuron plasticity.

PMID- 1356266
TI  - Chromosome location of Oryza sativa recombination linkage groups.
AB  - In situ hybridization, a powerful tool for the molecular cytogeneticist, can be
      used to physically map repetitive, low-copy, and unique DNA sequences in plant
      chromosomes. With the availability of a recombination map in Oryza sativa L. and
      an improved in situ hybridization technique, this study was designed to establish
      the relationship between the genetic and physical distances of the rice
      restriction fragment length polymorphism map. Analysis indicated that
      considerable variation can exist between genetic and physical maps. A 183
      centimorgan linkage map for chromosome 2 covered less than 50% of the chromosome
      and did not include the centromere, whereas a 91-centimorgan linkage map for
      chromosome 1 covered approximately 80% of the chromosome. The results indicated
      that there are potential "hot" and "cold" spots of recombination and
      polymorphisms in rice, which involve both genes and restriction fragment length
      polymorphisms.

PMID- 1356268
TI  - Class-level relationships in the phylum Cnidaria: evidence from mitochondrial
      genome structure.
AB  - The phylogenetic relationships of the Recent cnidarian classes remain one of the
      classic problems in invertebrate zoology. We survey the structure of the
      mitochondrial genome in representatives of the four extant cnidarian classes and
      in the phylum Ctenophora. We find that all anthozoan species tested possess mtDNA
      in the form of circular molecules, whereas all scyphozoan, cubozoan, and
      hydrozoan species tested display mtDNA in the form of linear molecules. Because
      ctenophore and all other known metazoan mtDNA is circular, the shared occurrence
      of linear mtDNA in three of the four cnidarian classes suggests a basal position
      for the Anthozoa within the phylum.

PMID- 1356267
TI  - Identification, characterization, and DNA sequence of a functional "double" groES
      like chaperonin from chloroplasts of higher plants.
AB  - Chloroplasts of higher plants contain a nuclear-encoded protein that is a
      functional homolog of the Escherichia coli chaperonin 10 (cpn10; also known as
      groES). In pea (Pisum sativum), chloroplast cpn10 was identified by its ability
      to (i) assist bacterial chaperonin 60 (cpn60; also known as groEL) in the ATP
      dependent refolding of chemically denatured ribulose-1,5-bisphosphate carboxylase
      and (ii) form a stable complex with bacterial cpn60 in the presence of Mg.ATP.
      The subunit size of the pea protein is approximately 24 kDa--about twice the size
      of bacterial cpn10. A cDNA encoding a spinach (Spinacea oleracea) chloroplast
      cpn10 was isolated, sequenced, and expressed in vitro. The spinach protein is
      synthesized as a higher molecular mass precursor and has a typical chloroplast
      transit peptide. Surprisingly, however, attached to the transit peptide is a
      single protein, comprised of two distinct cpn10 molecules in tandem. Moreover,
      both halves of this "double" cpn10 are highly conserved at a number of residues
      that are present in all cpn10s that have been examined. Upon import into
      chloroplasts the spinach cpn10 precursor is processed to its mature form of
      approximately 24 kDa. N-terminal amino acid sequence analysis reveals that the
      mature pea and spinach cpn10 are identical at 13 of 21 residues.

PMID- 1356270
TI  - Adipogenic cell line TA1: a suitable model to study the effect of beta-adrenergic
      agonists on lipid metabolism.
AB  - The stable adipogenic cell line TA1 was investigated as a potential in vitro
      system to examine effects of beta-adrenergic agonists on lipid metabolism at the
      cellular level. Initial experiments were conducted to establish whether
      dexamethasone, indomethacin, or both in combination induce rapid differentiation
      of TA1 preadipocytes to adipocytes. Based on activity of fatty acid synthase,
      dexamethasone and indomethacin, individually and in combination, were observed to
      induce differentiation in TA1 cells at different rates
      (dexamethasone/indomethacin greater than indomethacin greater than
      dexamethasone). Dexamethasone/indomethacin induced complete differentiation in
      TA1 cells 4 days after confluence, as indicated by increased activity of fatty
      acid synthase, glycerol-3-phosphate dehydrogenase, and malic enzyme. Finally,
      mature TA1 adipocytes were treated with various concentrations of isoproterenol
      and ractopamine to determine the responsiveness of TA1 adipocytes to a beta
      adrenergic challenge. Glycerol release was increased and fatty acid synthase
      activity was decreased in a dose-dependent manner for both isoproterenol and
      ractopamine. These results indicate that fully differentiated TA1 adipocytes may
      be useful to study direct cellular effects of lipolytic and lipogenic agents on
      lipid metabolism.

PMID- 1356271
TI  - Comparative molecular carcinogenesis. Proceedings of the 5th International
      Conference on Carcinogenesis and Risk Assessment. Austin, Texas, November 19-22,
      1991.

PMID- 1356269
TI  - Developmentally regulated Drosophila gene family encoding the fork head domain.
AB  - We have isolated seven Drosophila genes by means of low-stringency hybridization
      to a DNA probe containing the coding sequence for the protein domain shared by
      the rodent hepatocyte-enriched nuclear transcription factor HNF3A (alpha) and the
      product of the Drosophila region-specific homeotic gene fork head (fkh). The
      previously unreported genes encode a 110-amino acid conserved sequence, which we
      call the fork head (fkh) domain. Two of these fkh-domain-encoding genes ("FD
      genes") map to the sloppy paired locus (slp), which exerts segmentation gene
      function. The expression patterns of the other FD genes suggest that their
      protein products are likely to be involved in gut formation, mesoderm
      specification, and some specific aspects of neural development. The FD gene
      products presumably represent a family of transcription factors that, like the
      previously identified DNA-binding proteins, contribute to early developmental
      decisions in cell fates during embryogenesis.

PMID- 1356272
TI  - Aminorex produces stimulus effects similar to amphetamine and unlike those of
      fenfluramine.
AB  - A 4-methyl derivative of aminorex has recently appeared on the clandestine market
      as a designer drug. In the present study, the stimulus effects of aminorex itself
      were evaluated in rats trained to discriminate either 0.75 mg/kg S(+)-amphetamine
      or 1.5 mg/kg fenfluramine from saline. The amphetamine stimulus (ED50 = 0.14
      mg/kg) generalized to aminorex (ED50 = 0.23 mg/kg), which was found to be
      slightly less potent than (+)-amphetamine. Fenfluramine stimulus generalization
      did not occur to aminorex. Thus, the stimulus effects of aminorex are
      qualitatively similar to those of amphetamine and unlike those of fenfluramine.

PMID- 1356273
TI  - NMDA receptor inhibition prevents tolerance to cocaine.
AB  - Male rats were treated with cocaine by utilizing two different experimental
      paradigms. One group of animals received a low dose (10 mg/kg, IP) of cocaine for
      7 days. A second group received 40 mg/kg IP of cocaine for 3 days. In both
      experimental groups, half the animals were concomitantly treated with 0.25 mg/kg
      IP (+)-5methyl-10,11-dihydro-5H-dibenzo-[a,d]-cyclohepten-5,10- imine maleate (MK
      801), a noncompetitive NMDA receptor antagonist. Rats treated with the low dose
      of cocaine after 7 days developed tolerance to the stimulation of locomotor
      activity induced by cocaine and by the dopamine D2 agonist quinpirole. Rats
      treated with 40 mg/kg of cocaine showed a marked behavioral sensitization. Both
      these effects, tolerance and sensitization, were prevented by coadministration of
      MK-801, thus suggesting these two phenomena are different aspects of a common
      neuronal response in which NMDA transmission plays a crucial role.

PMID- 1356274
TI  - Increased sexual behavior in male Macaca arctoides monkeys produced by
      atipamezole, a selective alpha 2-adrenoceptor antagonist.
AB  - The effect of a highly selective and potent alpha 2-adrenoceptor antagonist,
      atipamezole, on sexual behavior was studied in three stumptail macaques (Macaca
      arctoides). Following IM administration of atipamezole or saline control, the
      behavior of the male monkey with a female monkey was observed for 30 min.
      Atipamezole dose dependently (0.01-0.15 or 0.30 mg/kg) produced a significant
      increase in the number of ejaculations in all three monkeys, including an old one
      with decreased sexual activity in control conditions. Both ejaculations obtained
      by copulation and masturbation were increased. It is concluded that atipamezole
      is effective in increasing sexual behavior in male stumptail monkeys.

PMID- 1356275
TI  - Reversal of cirazoline- and phenylpropanolamine-induced anorexia by the alpha 1
      receptor antagonist prazosin.
AB  - Phenylpropanolamine (PPA) is a phenethylamine anorectic drug that exerts direct
      agonist effects predominantly on alpha 1-adrenoceptors, with some alpha 2
      adrenergic activity. Microinjections of PPA, as well as the alpha 1-adrenergic
      receptor agonists cirazoline, methoxamine, and 1-phenylephrine, into rat
      paraventricular nucleus (PVN) suppress feeding. The present study further
      evaluates the alpha 1-adrenergic basis of PPA-induced anorexia by examining the
      effects of systemic injections of the alpha 1-adrenergic antagonist prazosin
      (PRAZ, 2 and 5 mg/kg, IP) on the anorexia induced by systemic injections of PPA
      (5, 10, and 20 mg/kg, IP), as well as cirazoline (0.05, 0.1, and 0.2 mg/kg, IP).
      Although neither PRAZ dose alone altered food intake in the present study, 2
      mg/kg PRAZ effectively reversed the feeding-suppressive effects of both PPA and
      cirazoline. These results strongly support the hypothesis that alpha 1
      adrenoceptor stimulation mediates the anorexia induced by drugs such as PPA and
      cirazoline.

PMID- 1356276
TI  - Benzodiazepines: use, abuse, and consequences.

PMID- 1356278
TI  - Effect of sulfasalazine on adaptive and functional changes in intestine of normal
      and protein-calorie-malnourished rats.
AB  - The effects of sulfasalazine (500 mg/kg body weight daily for 35 days) and its
      subsequent recovery for another 35 and 65 days have been investigated on the
      intestinal uptake of certain end-product nutrients, viz. glucose, leucine,
      alanine, and calcium, in normal and protein-calorie malnourished (PCM) male
      albino rats. Sulfasalazine administration caused a reduction in body weight in
      PCM animals, while intestinal weight and length as well as protein and nucleic
      acid contents were reduced in both normal and PCM animals. Serum proteins also
      showed a decrease in PCM rats. PCM rats showed elevated levels of glucose, amino
      acids, and calcium uptake by the intestinal segments, but sulfasalazine feeding
      inhibited the uptake of nutrients both in normal-fed and malnourished animals.
      All these changes were found to be reversible after the withdrawal of drug
      treatment. Sulfasalazine caused a decrease in the Na(+)-dependent (active)
      glucose uptake as well as the Na(+)-independent (passive) process. The kinetic
      parameters of glucose uptake indicate that the drug might interfere with the
      transport/carrier protein of these nutrients, because reduction was observed in
      maximum uptake velocity (Jmax) of these systems without any change in the
      affinity constant (Kt).

PMID- 1356279
TI  - An HIV-positive gravida needs treatment too.

PMID- 1356277
TI  - Alpidem and lorazepam in the treatment of patients with anxiety disorders:
      comparison of physiological and psychological effects.
AB  - The physiologcal and psychological effects of the novel imidazo-pyridine alpidem
      were compared with those of the benzodiazepine lorazepam in the context of a
      clinical trial. Twenty-three psychiatric out-patients with generalised anxiety
      disorder received alpidem (mean dose 112.5 mg daily) or lorazepam (mean 3.5 mg
      daily) in doses adjusted to clinical need under double-blind conditions. A
      battery of tests was performed before and after four weeks treatment. Anxiety
      scores improved very significantly in both groups with no subjective sedation nor
      other particular side-effects noted in either group. However, lorazepam reduced
      the EEG averaged evoked response and produced significant impairment in the
      reaction time and memory tests whereas alpidem had no such effects. Alpidem
      therefore shows promise as an effective anxiolytic devoid of the adverse
      psychomotor and cognitive effects often associated with the benzodiazepines.

PMID- 1356280
TI  - [The child as patient].

PMID- 1356281
TI  - HLA-DQA1 and MLC among HLA (generic)-identical unrelated individuals.
AB  - We modified a previously published PCR-RFLP for DQA1 typing (1) and examined the
      predictive value of HLA-DQA1 in mixed lymphocyte cultures (MLC) among matched
      (HLA generic types) pairs of unrelated individuals. There were 61/102 (60%) pairs
      with positive MLC, one-third of which could be predicted by DQA1* typing alone.
      DQA1 matching and MLC reactions were classified into 3 groups: 1) DQA1 mismatches
      showing positive MLC: 19/102 (19%); 2) DQA1 matches showing negative MLC: 41/102
      (40%); 3) DQA1 identical showing positive MLC: 42/102 (41%). Five different HLA
      haplotypes that result from non-random association of HLA generic types (high
      delta haplotypes) were overrepresented in the individuals tested. One of these
      haplotypes carrying HLA-B7, DR2 was found associated with three different DQA1
      alleles (*0201, *0103, *0102). The remaining four high delta haplotypes were
      associated with one DQA1 allele in all independent examples tested: HLA-A1, B8,
      DR3 with DQA1*0501; HLA-A26, B38, DR4 with DQA1*0301; HLA-A2, Bw62, DR4 with
      DQA1*0301 and HLA-A1, Bw57, DR7 with DQA1*0201. Forty per cent of the negative
      MLC were explained in part by the excessive number of individuals carrying two of
      these four haplotypes, which probably carry determinants in linkage
      disequilibrium with HLA. Nineteen per cent of HLA-identical (generic types)
      unrelated pairs show positive MLC reactions and all of them are DQA1* mismatched,
      suggesting that DQA1* allele typing should be used to screen samples prior to
      performing MLC.

PMID- 1356282
TI  - HLA-DRB1 genotyping by modified PCR-RFLP method combined with group-specific
      primers.
AB  - We previously introduced HLA-DQA1, -DPB1 and DQB1 genotyping with the modified
      PCR-RFLP method using some informative restriction enzymes which have either a
      single cleavage site or alternatively no cleavage site in the amplified DNA
      region, depending on the HLA alleles, making reading of RFLP band patterns much
      easier. In this study, 43 HLA-DRB1 alleles, excluding DRB1*1103 and *1104 for
      which no restriction enzymes are available to distinguish each from the other,
      could be defined by this modified PCR-RFLP method combined with 7 pairs of group
      specific primers. It is impossible to distinguish DRB1*0701 and DRB1*0702 as they
      are identical for the second exon of DRB1. For DR1-DRB1, DR2-DRB1, DR4-DRB1, DR7
      DR1, DR9-DRB1, DRw10-DRB1 or DRw52 associated antigens (DR3, w11, w12, w13, w14,
      and DRw8)-DRB1 gene amplification, the second exon of the DRB1 gene was
      selectively amplified using each group-specific primer from genomic DNAs of 70
      HLA-homozygous B-cell lines and healthy Japanese by PCR. Amplified DNAs were
      digested with restriction endonucleases and then subjected to electrophoresis
      assaying simply for cutting, or no cutting, of the DNA, although some alleles can
      be distinguished only after examination of RFLP band patterns generated and in
      some cases using double digestion technique with two restriction enzymes. This
      modified PCR-RFLP method can be successfully applied to all possible DRB1
      heterozygotes, despite the fact that 15 pairs of heterozygotes among them cannot
      be distinguished theoretically by the PCR-SSO method, because the PCR-RFLP method
      can tell whether two polymorphic sites are linked to each other (cis position) or
      located on a different chromosome (trans position) by checking the length of RFLP
      bands generated with double digestion. Thus, the PCR-RFLP method is technically
      simple, practical and inexpensive for determination of the HLA-DRB1 alleles for
      routine HLA typing work.

PMID- 1356283
TI  - HLA-DPB1 allele mismatches between unrelated HLA-A,B,C,DR (generic) DQA1
      identical unrelated individuals with unreactive MLC.
AB  - We have used a PCR-RFLP method with one generic amplification of HLA-DPB1 second
      exon and 6 endonucleases to differentiate the 19 HLA-DPB1 alleles and 171
      heterozygous combinations. The set of primers used in our studies produced
      fragment sizes different from those published before (1). The HLA-DPB1 alleles in
      Caucasians showed a higher frequency of DPB1*0401 and DPB1*0402, when compared to
      a small group of Colombians who showed a higher frequency of DPB1*0402 and
      DPB1*0201. We found three HLA-DPB1 alleles associated with two HLA haplotypes
      that result from non-random association of alleles: DPB1*0401 with HLA-A26, B38,
      DR4, DQA1*0301 and DPB1*0101 and DPB1*0401 with HLA-A1, B8, DR3, DQA1*0501. We
      also report that 70% of combinations between HLA (generic A,B,C,DR) and DQA1
      identical MLC-unreactive cell mixtures showed HLA-DPB1 mismatches, suggesting
      that HLA-DPB1 differences are not important in MLC reactivity.

PMID- 1356285
TI  - Education gets an airing at Scarborough.

PMID- 1356284
TI  - Block and modulation of cardiac Na+ channels by antiarrhythmic drugs,
      neurotransmitters and hormones.
AB  - The Na+ channel is an important target for the action of antiarrhythmic drugs.
      Application of contemporary biophysical, biochemical and molecular biological
      techniques have added considerably to our knowledge of its structure, function,
      modulation and block by antiarrhythmic drugs. The increased mortality from the
      use of these drugs for prophylaxis of cardiac arrhythmias has forced a re
      evaluation of their use and of the entire pharmacological strategy of arrhythmia
      management. Gus Grant and David Wendt review recent studies on the block and
      modulation of cardiac Na+ channels and the place of Na+ channel blockers in
      future antiarrhythmic drug development.

PMID- 1356286
TI  - EBV strain variation: geographical distribution and relation to disease state.
AB  - The strains of Epstein-Barr virus (EBV) were characterized in epithelial and
      lymphoid malignancies from geographic regions with high or low incidence. The
      predominant strains in nasopharyngeal carcinoma (NPC) from regions with elevated
      incidence were EBV type 1 in southeast Asia and Mediterranean Africa. In Alaskan
      Eskimos, a distinct variant of EBV type 2 was found in NPC and carcinoma of the
      parotid gland. This strain contained polymorphisms characteristic of the Asian
      EBV type 1. The strains prevalent in southeast Asia and Mediterranean Africa were
      also found in NPC which developed in caucasian Americans. These variants were not
      detected in lymphomas which developed in central Africa, Mediterranean Africa, or
      continental United States. These results suggest that distinct EBV strains
      predominate in geographic areas with elevated incidence of NPC. The detection of
      these distinct strains in epithelial tumors from areas of low incidence may
      reflect an epithelial cell tropism or pathogenicity.

PMID- 1356287
TI  - Evidence that a cytoplasmically located version of a v-erbB-encoded protein can
      transform both fibroblasts and erythroblasts.
AB  - We previously isolated an avian erythroblastosis virus, AEV-GEE35, in which the
      complete extracellular and transmembrane domains of the v-erbB oncoprotein were
      replaced with sequences from the gag and env proteins. The GEE35 virus was
      capable of transforming both fibroblasts and erythroblasts as efficiently as wild
      type v-erbB. Analysis of the v-erbB proteins encoded by GEE35 revealed two
      proteins of similar molecular weights of approximately 130,000 Da. One of these
      proteins was an N-linked glycosylated membrane protein, whereas the other was a
      cytoplasmic protein. Biochemical characterization of these two proteins revealed
      that the transmembrane protein has the v-erbB domain outside the cell, such that
      it no longer had access to its tyrosine kinase substrates. This implies that it
      is the cytoplasmically located v-erbB-encoded protein that is responsible for the
      efficient transforming ability of this virus.

PMID- 1356288
TI  - [The results of the All-Army Scientific Conference on the Experience of Medical
      Support for the Soviet Troops in Afghanistan and the Problems in the Further
      Development of Military Medicine].

PMID- 1356289
TI  - [Epidemiologic characteristics of hemorrhagic fever with renal syndrome in a
      military population].
AB  - In the period 1952-1990 there have been recorded 84 patients with hemorrhagic
      fever with renal syndrome (HFRS): 81 soldiers and 3 officers of the Y.P.A. The
      largest number of cases was recorded in three epidemics, 61 or 72.6%. In 94% of
      cases the infection occurred during camping of units. The disease appeared in all
      months, but 57.2% of cases occurred in June and July. The mean lethality was
      2.4%, in epidemics 1.6% and as sporadic cases 4.3%. In an army unit staying for
      six months in HFRS focus, 9.8% of soldiers were infected by the causative agent
      of this infection and only in one case the clinical picture of HFRS was
      manifested. Serologic tests (IIF and ELISA) confirmed the diagnosis of HFRS.
      Virus strains of Hantaan, Puumala and Seoul groups were used as antigens.

PMID- 1356290
TI  - Domains 1 and 2 of ICAM-1 are sufficient to bind human rhinoviruses.
AB  - The intercellular adhesion molecule-1 (ICAM-1) receptor was expressed in primary
      chicken embryo cells using a retroviral vector and shown to specifically bind
      major group human rhinoviruses (HRVs). A truncated, membrane-bound ICAM-1 protein
      containing N-terminal domains 1, 2, and 3 retained the ability to bind virus
      whereas proteins containing domains 1 and 2 or domain 1 were not expressed under
      these conditions. Soluble forms of ICAM-1 proteins were expressed to circumvent
      the reduced expression levels of shorter ICAM-1 truncations. Full-length and
      truncated ICAM-1 molecules containing only domains 1 and 2 were capable of
      neutralizing HRV binding to cells. Soluble receptors containing only domain 1
      could not be recovered. Mutants of ICAM-1 lacking carbohydrate attachment sites
      were constructed and shown to have no effect on the ability of ICAM-1 to bind
      HRVs. In addition, ICAM-1 proteins expressed in the presence of tunicamycin also
      retained their virus binding capability. These data suggest that the N-terminal
      two domains of ICAM-1 are sufficient for virus interaction and that carbohydrates
      do not play a major role in virus binding.

PMID- 1356291
TI  - Psychotropic drug use in pregnancy and perinatal death.
AB  - The psychotropic drug use in mothers to all 73 perinatally dead infants in the
      city of Gothenburg, Sweden, in 1985-86, was compared to a control group of
      mothers to 73 surviving infants. Information regarding medication in pregnancy
      and pre- and perinatal data was collected retrospectively. In addition, serum
      samples obtained in early pregnancy were screened for benzodiazepines. Eighteen
      case-mothers used psychotropic drugs during pregnancy compared with 7 control
      mothers. The association between psychotropic drug use and perinatal death was
      significant (p = 0.01). Psychotropic drug use and maternal disorder were closely
      correlated, but within the case group there were no significant differences
      between mothers using or not using psychotropic drugs in terms of age, parity or
      smoking habits. Although the etiology of death could be discussed in the
      individual infant, we find it noteworthy that the use of psychotropic drugs was
      so frequent in the mothers of perinatally dead infants.

PMID- 1356292
TI  - Effect of atrial natriuretic factor on renal prostaglandin E2 release in the
      anaesthetized dog.
AB  - Experiments were undertaken in two groups of barbiturate anaesthetized dogs to
      examine whether atrial natriuretic factor (ANF) exerts an effect on renal release
      of prostaglandin E2 (PGE2). In the first group, intravenous infusion of ANF (50
      ng min-1 kg-1 body wt) reduced basal PGE2 release from 4.4 +/- 0.8 pmol min-1 to
      1.8 +/- 0.7 pmol min-1. In the second group, intrarenal infusion of an alpha 1
      adrenoceptor agonist, phenylephrine (2.5-6.75 micrograms min-1), raised PGE2
      release from 2.7 +/- 0.5 pmol min-1 to 7.5 +/- 1.3 pmol min-1. During continuous
      alpha 1-adrenergic stimulation, intravenous infusion of ANF (100 ng min-1 kg-1
      body wt) reduced PGE2 release to 3.5 +/- 1.0 pmol min-1. These results
      demonstrate that ANF reduces basal and alpha 1-adrenergic stimulated renal PGE2
      release.

PMID- 1356294
TI  - Excitation-contraction coupling in skeletal, cardiac, and smooth muscle.
      Proceedings of the 3rd international symposium. Banff, Alberta, Canada, June 26
      30, 1991.

PMID- 1356295
TI  - Energetics of muscarinic stimulation of smooth muscle.

PMID- 1356293
TI  - [Azaspirodecanodiones in clinical psychiatry].
AB  - The authors achieve a review of some clinical and therapeutic features related to
      the use of azaspirodecanodiones (buspirones, gepirone, ipsapirone). Buspirone-
      the only one available--is a novel nonbenzodiazepine anxiolytic that shows
      affinity for the serotonin 1A receptor subtype, acting as a partial agonist in
      the serotonergic system. This review attempts to put up to date the therapeutic
      studies of azaspirodecanodiones--especially buspirone--in anxiety (panic
      disorder, generalized anxiety disorder, obsessive-compulsive disorder),
      depression abuse and dependence of substances and other neuropsychiatric
      disorders. Though its main indication is generalized anxiety disorder, it may be
      also useful in treating other disorders and multiple psychopathologies related to
      serotonergic system dysfunctions, such as depression or alcoholism. Other
      interesting feature of buspirone is its potential usefulness in anxious elderly
      patients and long-term therapy.

PMID- 1356296
TI  - Alpha-mediated vasoconstriction: transmembrane signalling and receptor
      reclassification.
AB  - Apparent differences in the usage of different calcium pools for the processes of
      excitation-contraction provides support for further sub-classification of the
      alpha-adrenoceptors in blood vessels. Presently we have addressed this question
      by assessing the routes of calcium utilization and the involvement of G-proteins
      in mediating vasoconstriction in situ.

PMID- 1356297
TI  - Hepatic glutathione degradation within the sinusoids of guinea pig livers shows a
      periportal localization of gamma-glutamyl transferase activity.
AB  - In utilizing intact perfused guinea pig livers a probable periportal localization
      of gamma-glutamyl transferase (GGT) activity was apparent. Untreated livers
      perfused from the portal to hepatic vein had a significantly greater glutathione
      efflux than the same livers perfused from the hepatic to portal vein. Switching
      the perfusion direction also saw a significant rise in the cysteinylglycine
      efflux. It was apparent from the results that the efflux of glutathione
      degradation products from the guinea pig livers was significantly greater than
      those of the intact tripeptide. However, with maximal GGT inhibition glutathione
      accounted for 90% of the glutathione-related thiols exported from the liver with
      cysteine accounting for the remaining 10%. Therefore, glutathione exported from
      hepatocytes may act as a means of transporting its constituent amino acids. The
      periportal localization of GGT activity ensures that the more susceptible
      perivenous region faces the greatest concentration of glutathione degradation
      products.

PMID- 1356298
TI  - Seasonality of adult Culex quinquefasciatus and transmission of bancroftian
      filariasis in Pondicherry, south India.
AB  - Seasonal variations in biting Culex quinquefasciatus and transmission of
      bancroftian filariasis were investigated in Pondicherry, South India. The biting
      density of C. quinquefasciatus, the principal vector species, was lowest in the
      summer months and higher during the monsoon and winter months. The survival of
      the vectors as indicated by the proportion of parous mosquitoes was found to be
      less in the summer season. Biting mosquitoes with infective stage larvae were not
      encountered during the hottest months of May, June and July and the early monsoon
      month of August indicating seasonality of transmission. Maximum transmission took
      place between November and March. These findings suggest that vector control
      measures according to the season of transmission may produce more cost-effective
      results than year round control operations.

PMID- 1356299
TI  - Attenuation of malaria infection, paralysis and lesions in the central nervous
      system by low protein diets in rats.
AB  - Young Wistar rats developed a fulminant infection when inoculated with the rodent
      malaria parasite Plasmodium berghei. Rats that died during the infection
      exhibited a progressive paralysis of the extremities, a rapidly decreasing body
      temperature and minute haemorrhages in the brain. Increasing the level of protein
      in the diet from 4 to 8 and 16% was accompanied by an increase in morbidity and
      mortality from 15 to 40 and 90% respectively on day 6 of the infection.
      Increasing the level of dietary protein also increased the reticulocyte count of
      the peripheral blood in infected and non-infected rats. The attenuation of the
      cerebral syndrome in rats fed a diet low in protein may be related to changes in
      erythropoiesis or to changes in immune reactivity.

PMID- 1356300
TI  - Relationships between circulating S-antigens, naturally acquired antibodies to
      Plasmodium falciparum exoantigens and malaria attack in a mesoendemic area.
AB  - A survey involving 77 individuals living in two savannah villages near Bobo
      Dioulasso (Burkina Faso, West Africa), was performed in June 1987 (before),
      August-September (during) and January 1988 after the seasonal transmission. The
      clinical longitudinal study during the seasonal period permitted us to define
      three different groups in terms of both age and occurrence of malaria attack (MA;
      greater than or equal to 5000 parasites/mm3 of blood and axillary fever greater
      than or equal to 37.8 degrees C). The presence of circulating stable antigen (S
      Ag) and the antibody responses against exoantigens (E-Ag) of Plasmodium
      falciparum were also evaluated at three observations periods: beginning, during
      and after the transmission season. The adult group (III) had the highest rates of
      IgG Ab to E-Ag although, IgM prevalence to E-Ag was maximal in the group II
      (individuals with no malaria attack and age less than or equal to 15 years old).
      Group I (persons with less than or equal to 15 years old and who contracted at
      least one MA) did not have any S-Ag at the first observation period and showed
      the lowest rate of antibodies to E-Ag. The probability of occurrence of an MA
      calculated from these parameters at the beginning of the transmission period were
      correct in 78.9% of the cases in children (Groups I & II) and in 71.8% of adults
      during the subsequent transmission period. Therefore these values could be used
      for evaluating the probability of occurrence of a clinical MA during the
      transmission period in a mesoendemic area. S-Ag and antibodies to E-Ag could
      participate positively in the mechanisms involved in the development of the
      immune status.

PMID- 1356301
TI  - Eating habits of east Asian people and transmission of taeniasis.
AB  - In order to understand the role of raw meat and viscera eating habits in the
      transmission of taeniasis in Asian countries, 1502 infected aborigines in ten
      mountainous districts/towns of six counties in Taiwan, 58 infected persons in two
      villages on Cheju Island, Korea, and 97 cases in Ambarita District on Samosir
      Island, North Sumatra, Indonesia were studied during the field surveys. All
      infected Taiwan aborigines had the habit of eating raw meat and viscera of wild
      and/or domestic animals. Among these aborigines, 73% ate wild boar, 66% flying
      squirrel, 65% wild goat, 56% muntjac, 49% wild rats, 46% monkey, 38% hare, 20%
      civet-cats, 18% weasel, 17% pheasant, 14% squirrel, 4% grouse, 1% deer, 1% snake,
      less than 1% bamboo partridge, less than 1% frog, less than 1% bear, less than 1%
      dog, and less than 1% fox. Of the 58 infected persons with Taenia on Cheju
      Island, Korea, 72% ate raw meat and/or viscera of pig and cattle, 19% raw pork
      only, and 9% raw beef only. Among 12 infected persons infected with T. saginata
      like tapeworms, 7 had eaten raw pork, 2 raw beef and pork and 3 raw pork. Almost
      all of the 97 cases of taeniasis on Samosir Island of North Sumatra, Indonesia,
      had eaten only undercooked pork. Eleven of 15 cases were found to be infected
      with T. saginata-like tapeworms. Eating habits observed suggest an unusual way of
      transmission of Taenia in East Asia.

PMID- 1356302
TI  - Schistosoma haematobium infection in pregnancy.
AB  - Due to the economical lack of safe drugs in a remote area of Ghana (Bawku
      District) to treat Schistosoma haematobium infection during pregnancy, the
      spontaneous outcome of the pregnancy in women with proved S. haematobium
      infection was compared with a control group (average hospital delivery). In a
      survey of 200 pregnant women, we found a prevalence of S. haematobium of 4.5%.
      From the original collection of 41 infected pregnant women we could follow 23 up
      to delivery. This group showed a higher number of preterm (less than 37 weeks)
      deliveries, 34.8% vs. 23.8% in the control group. The birthweights in term
      deliveries (greater than 37 weeks) were not significantly different (3012 g vs.
      3103 g). In the preterm deliveries the birthweight was significantly lower in the
      infected group (1768 g vs. 2457 g, p less than 0.005).

PMID- 1356303
TI  - A decade of plague epidemiology and control in the western Usambara mountains,
      north-east Tanzania.
AB  - Outbreaks of human plague have been occurring in the Western Usambara mountains
      since 1980, involving many cases and deaths. Epidemiological surveys and control
      activities were carried out from June 1980 to May 1990. Rodents were trapped
      live, identified and serologically tested for plague, using the passive
      haemagglutination and passive haemagglutination inhibition tests. Rodent fleas
      were collected, processed, identified and counted. House fleas were caught with
      light traps and similarly treated. People and domestic carnivores were
      serologically tested for the disease. Various plague control measures were
      undertaken. A total of 2433 animals, 2254 rodent fleas and 1366 house fleas were
      collected. Average indices of rodent and house fleas were 0.93 and 5.38
      respectively. Rattus rattus and Mastomys natalensis were the most abundant rodent
      species. Xenopsylla brasiliensis and Dinopsyllus lypusus were their commonest
      flea ectoparasites while Pulex irritans was the major house flea. Of 2044 rodent,
      1880 human and 176 dog sera tested, 5.5%, 0.5% and 6.3% respectively were
      positive. It was concluded that plague was active in the focus despite the
      control measures and that common reservoirs and efficient vectors were present.
      It was suggested that dogs were probably involved in the epidemiology of the
      disease, that P. irritans was not susceptible to the insecticide used and that
      the flea was probably involved in murine plague transmission. Bacteriological
      research on the causative agent to establish the nature of its long persistence
      in the area and maintenance of a surveillance service are recommended.

PMID- 1356304
TI  - Inhibition of the growth of Plasmodium falciparum and Plasmodium berghei in vitro
      by an extract of Cochlospermum angolense (Welw.).
AB  - An extract of Cochlospermum angolense (Welw.) is used in the traditional medicine
      of Angola for the therapy of icterus and for the prophylaxis of malaria. From the
      roots of this plant red crystalline substances have been isolated and tested for
      their effect on Plasmodium falciparum in vitro and on the DNA and protein
      synthesis of Plasmodium berghei. The multiplication of P. falciparum was
      decreased to 50% of the control in the presence of 10 micrograms/ml extracted
      material and there was a total inhibition at a concentration of 50 micrograms/ml.
      If mice erythrocytes infected by P. berghei were incubated for 6 h with 25
      micrograms/ml of the extract DNA synthesis was depressed to nearly background
      level. And, even more important, this effect could be demonstrated immediately.
      On the contrary, protein synthesis continued for at least 90 min at a reduced
      rate and stopped then. The results obtained show the direct antiparasitic effect
      of the substances extracted from C. angolense. The activity seems to be directed
      against DNA synthesis.

PMID- 1356305
TI  - Nosocomial fungal infections--study of the possible role of cockroaches
      (Blattella germanica) as vectors.
AB  - A variety of fungi of medical importance were recovered from cockroaches
      (Blattella germanica) collected from hospital wards (159) and residential areas
      (128) in different seasons. The fungi isolated were various species of Candida,
      Rhizopus, Mucor, Alternaria and Aspergillus. Candida spp. were the fungi isolated
      in highest percentage from hospital and residential area.

PMID- 1356307
TI  - Antigenic mimicry between piperazine derivatives and Wuchereria bancrofti
      microfilariae.

PMID- 1356306
TI  - Sequential infection of tsetse flies with Trypanosoma congolense and Trypanosoma
      brucei.
AB  - The question whether tsetse flies can be experimentally infected with more than
      one trypanosome species or strain by sequential feeding was investigated using
      DNA probe technology to identify directly the small numbers of trypanosomes in
      the fly gut. Bloodstream form trypanosomes of Trypanosoma congolense or T. brucei
      ssp. were used for initial infection, followed by sequential feeds using either
      T. congolense or T. brucei ssp. Midgut trypanosome populations were subsequently
      analysed by hybridising dot blots with species-specific DNA probes. Two different
      T. brucei stocks were also fed in succession and the midgut trypanosome
      populations analysed by molecular karyotype. Contrary to expectations from
      previous reports, it was comparatively easy to superinfect flies with a second
      trypanosome species or stock, although the presence of trypanosomes already in
      the gut did not aid establishment of those incoming. Thus, to develop a mixed
      infection, a prerequisite for trypanosome mating, flies do not necessarily have
      to pick up both parental trypanosomes on their first feed.

PMID- 1356308
TI  - Two syntopic zymodemes of Leishmania infantum cause human and canine visceral
      leishmaniasis in the Naples area, Italy.

PMID- 1356309
TI  - Treatment of complete heart block with inhaled beta-agonists.

PMID- 1356310
TI  - Balloon angioplasty of the aorta in Takayasu's arteritis: initial and long-term
      results.
AB  - Percutaneous transluminal balloon angioplasty for stenosis of the aorta was
      performed in 36 patients with Takayasu's arteritis (age range, 8 to 36 years;
      mean, 19.1 +/- 7.7 years). Balloon dilatation was successful in 34 patients and
      resulted in a decrease in the mean peak systolic pressure gradient (PSG) from
      75.2 +/- 29.1 mm Hg to 24.8 +/- 19 mm Hg (p less than 0.001) and a mean increase
      in the diameter of the stenosed segments from 4.5 +/- 2.2 mm to 9.6 +/- 3.8 mm (p
      less than 0.001). Hemodynamic and angiographic restudy, which was performed in 20
      patients at a mean follow-up period of 7.7 +/- 4.1 months (range, 3 to 24
      months), showed a further decrease in PSG (greater than or equal to 15 mm Hg) in
      seven patients (from 40.0 +/- 11.2 mm Hg to 15.7 +/- 10.2 mm Hg; p less than
      0.01), no significant change in PSG in 12 patients (17.1 +/- 13.6 mm Hg vs 16.6
      +/- 12.7 mm Hg; p = NS), and an increase in PSG from 15 mm Hg to 85 mm Hg in one
      patient. The patient who showed restenosis underwent successful redilatation. Six
      patients who underwent late recatheterization and angiography at 36 to 60 months
      (mean, 43 +/- 9.4 months) show continued relief of stenosis (mean PSG, 8.8 +/-
      7.8 mm Hg). Patients with short-segment (less than 4 cm) stenosis experience more
      relief than patients with long-segment (greater than or equal to 4 cm) stenosis
      (residual PSG, 18.6 +/- 8.2 mm Hg vs 40 +/- 16 mm Hg; p less than 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1356311
TI  - Differential effects of xamoterol and verapamil on ventricular rate regulation in
      patients with chronic atrial fibrillation.
AB  - In a placebo-controlled study the effects on ventricular rate regulation and
      exercise performance of xamoterol, 100 mg two times a day and 200 mg two times a
      day, and slow-release verapamil, 240 mg once a day, were assessed in 21 patients
      with chronic atrial fibrillation. The mean ventricular rate from noon to 6:00 PM
      was 101 +/- 20 beats/min with placebo, 95 +/- 17 beats/min with xamoterol 100 mg
      two times a day (not significant), 90 +/- 16 beats/min with xamoterol 200 mg two
      times a day (p less than 0.001 vs placebo) and 78 +/- 19 beats/min with verapamil
      (p less than 0.001 vs each other treatment). The mean ventricular rate from
      midnight to 6:00 AM was 69 +/- 16 beats/min with placebo, increased with
      xamoterol 100 mg two times a day and 200 mg two times a day to 75 +/- 15
      beats/min and 74 +/- 16 beats/min, respectively (p less than 0.001 vs placebo),
      but decreased with verapamil to 62 +/- 15 beats/min (p less than 0.001 vs each
      other treatment). The number of ventricular pauses greater than 2.0 seconds was
      increased by verapamil (p less than 0.05). All active treatments reduced exercise
      ventricular rates (p less than 0.001), but the decrease was more pronounced with
      verapamil. The anaerobic threshold was reached significantly earlier with
      verapamil than with placebo (72 +/- 32 W vs 79 +/- 37 W; p less than 0.01).
      Xamoterol is preferable to verapamil for treatment of patients with chronic
      atrial fibrillation who exhibit both bradycardia at rest and excessive
      tachycardia during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356313
TI  - A symposium: 3rd North American Conference on Nitroglycerin Therapy. White
      Sulphur Springs, West Virginia, May 9-12, 1991.

PMID- 1356312
TI  - The effects of beta 1- and beta 2-adrenergic blockade and calcium channel
      blockade on postresuscitation electrolyte changes.
AB  - We have previously reported in dogs after ventricular fibrillation that (1)
      potassium and calcium levels decrease and magnesium and glucose increase, (2) all
      values return to control levels by 3 hours, and (3) propranolol blocks the
      changes in potassium, magnesium, and glucose but not calcium. The purpose of this
      study was to evaluate the beta 1- and beta 2-selectivity of changes in potassium,
      magnesium, and glucose and assess the response of the change in calcium to
      calcium channel blockade. Before initiating ventricular fibrillation, we
      pretreated dogs with an intravenous solution of either normal saline, metoprolol,
      ICI 118551 (two doses), or diltiazem. After a 2-minute episode of ventricular
      fibrillation, dogs were resuscitated. Baseline electrolyte measurements were
      obtained before ventricular fibrillation and sequentially for 3 hours after
      fibrillation. The saline-treated control group had a maximal decrease in the
      serum potassium level of 0.5 +/- 0.2 mEq/L. High-dose ICI 118551 reduced this
      decrease to 0.3 +/- 0.3 mEq/L (p = 0.055), but the other three groups showed no
      difference compared with the control group. Magnesium increased in the saline
      control group by 0.2 +/- 0.1 mEq/L. This increase was partially reduced by high
      dose ICI 118551 to 0.1 +/- 0.1 (p = 0.055) but not by the other drugs. Glucose
      increased to 40 +/- 13 mg/dl in the saline control group. This increase was
      partially reduced by high-dose ICI 118551 to 23 +/- 6 mg/dl (p = 0.007) but not
      by the other drugs. Calcium showed a maximal decrease of 0.6 +/- 0.3 mg/dl in the
      control group. This decrease was not attenuated by any of the drugs.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1356314
TI  - The influence of topography on the cognitive and psychopathological effects of
      tardive dyskinesia.
AB  - OBJECTIVE: The purpose of the study was to investigate the influence of the
      topography of dyskinetic movements on their effect on cognitive impairment and
      negative symptoms. METHOD: Eighty-four inpatients who satisfied DSM-III-R
      criteria for schizophrenia were rated for tardive dyskinesia, akathisia, and drug
      induced parkinsonism, as well as negative symptoms, with the Scale for the
      Assessment of Negative Symptoms and for cognitive state with the Mini-Mental
      State examination. The subjects were then divided into those without tardive
      dyskinesia (N = 45), those with orofacial dyskinesia (N = 19), and those with
      limb-truncal dyskinesia (N = 20). Differences among the groups were assessed with
      multiple analysis of covariance (MANCOVA), with age, akathisia, and drug-induced
      parkinsonism ratings as the covariates. Post hoc Spjotvoll and Stoline tests were
      then undertaken. RESULTS: MANCOVA revealed a significant difference among the
      groups. Post hoc tests showed that the group with limb-truncal dyskinesia had
      significantly lower scores on the Mini-Mental State Examination and higher scores
      on the Scale for the Assessment of Negative Symptoms. The group with orofacial
      dyskinesia was significantly different from the nondyskinetic group only on the
      total score for the Scale for the Assessment of Negative Symptoms and the
      attention subscale. There were no significant differences between the dyskinetic
      groups. CONCLUSIONS: After correction for the important confounding variables of
      age, akathisia, and drug-induced parkinsonism scores, those with limb-truncal
      and, to a lesser degree, orofacial dyskinesia differed significantly from
      nondyskinetic comparison subjects in ratings of cognitive impairment and negative
      symptoms.

PMID- 1356315
TI  - Molecular basis of clinical heterogeneity in neuroblastoma.
AB  - Neuroblastomas are heterogeneous in terms of both their genotype and their
      clinical behavior. Recent studies suggest that these two features are related,
      and that the genotype frequently is predictive of response to treatment or the
      outcome of the patient. The genetic abnormalities that are characteristic of
      certain neuroblastomas include: (a) loss of heterozygosity (LOH) for the short
      arm of chromosome 1, including band 1p36; (b) amplification of the N-myc
      protooncogene; and (c) hyperdiploidy, or near-triploidy, determined either by
      flow cytometry or by karyotype. Hyperdiploidy is associated with lower stages of
      the tumor and with a favorable outcome in infants. However, LOH for chromosome 1
      (band p36) and N-myc amplification are more common in patients over 1 year of age
      who have advanced stages of the tumor. Based on analysis of neuroblastomas for
      these genetic abnormalities, three distinct genetic subsets can be identified.
      The first is characterized by a hyperdiploid or near-triploid modal karyotype,
      with few, if any, cytogenetic rearrangements. These patients are generally less
      than 1 year of age, they have localized tumors, and have a good prognosis. The
      second genetic subset has a near-diploid karyotype, but with no consistent
      abnormality identified to date. They are generally older patients with tumors in
      the more advanced stages that progress slowly and are often fatal. Patients in
      the third group of genetic abnormalities have a near-diploid or tetraploid
      karyotype, with deletions or loss of heterozygosity for 1p36, amplification of N
      myc, or both. These patients are generally older; they have advanced stage tumors
      that are rapidly progressive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356317
TI  - Alcoholism and the D2 receptor gene.
AB  - The allelic association of the human dopamine D2 receptor gene and alcoholism was
      evaluated in 20 male alcoholics and 20 controls (sex, race, and geographic place
      of birth matched). This study further examines the issue of alcoholism severity
      and A1 allele frequency. No difference in A1 allele frequency was observed
      between these two groups. Similarly, no relationship between alcoholism severity
      and A1 frequency within the alcoholics was demonstrated.

PMID- 1356316
TI  - The associations of alcohol drinking and drinking cessation to measures of the
      immune system in middle-aged men.
AB  - To estimate the association between the immunologic responses of the cell
      mediated and humoral systems and alcohol drinking, we used data from the Vietnam
      Experience Study conducted by the Centers for Disease Control. That study,
      conducted from 1985 to 1986, was based on a random sample of 4462 male, Vietnam
      era, U.S. veterans. By using linear regression, we evaluated how (1) the number
      of alcoholic drinks the subjects consumed per month and (2) the drinking
      cessation of certain subjects were associated with their relative and absolute T,
      B, CD4, and CD8 lymphocyte counts and immunoglobulin A (IgA), IgM, and IgG
      levels. We used geometric means and percentage differences in geometric means of
      immune status to measure the associations and adjusted these values to account
      for the effect of covariates. The results indicated that measures of immune
      status differed among the drinking categories and that, generally, the
      differences changed after adjustment for covariates. These differences consisted,
      as alcohol consumption increased, of higher IgA and IgM levels, relative T and
      CD4 lymphocytes, and the ratio of CD4 to CD8 cells, and of lower IgG levels,
      relative B and CD8 lymphocytes, absolute lymphocyte, and lymphocyte subset counts
      after adjusting for other covariates. Among former drinkers, we found no clear
      cut pattern in measures of immunity for a few years after cessation and then
      found that values of former drinkers tended to return toward values of
      nondrinkers as they continued to abstain.

PMID- 1356318
TI  - Cryptorchidism: incidence and sperm quality in infertile men.
AB  - In a population of 8500 men attending the andrology outpatient clinic, 200 men
      (2.35%) were recorded as having some disturbances with the descent of the testes
      into the scrotum. Medical history of the patients revealed that 51 underwent
      unilateral orchidopexy; 40 bilateral orchidopexy; and 24 were treated with human
      chorionic gonadotropin in order to induce descent of their testes. In addition, 6
      patients reported spontaneous descent of the testes, and 13 others were found to
      be unilaterally cryptorchid upon physical examination. Results of semen analysis,
      hormonal profile, testes position, and testicular volume were compared to those
      of 105 proven fertile men. The major finding of this study shows that post-partum
      undescended testes suffer from primary Sertoli cell malfunction as reflected by
      elevated serum follicle stimulating hormone levels. Serum luteinizing hormone and
      testosterone levels were within the normal range. Surgical descent of the testes
      did not improve sperm production, proved by low sperm quality of all the study
      groups, compared to the cryptorchid group. Among the patients who were operated
      on, no correlation was found between age at operation and semen variables. All
      groups showed poor sperm quality which can be defined as
      oligoteratoasthenozoospermia. The degree of spermatogenic damage was in the
      following order of diagnosis or treatment: bilateral orchidopexy greater than
      cryptorchid testes greater than hormonal treatment greater than unilateral
      orchidopexy greater than late spontaneous descent of the testes. Thus, it is
      advisable to postpone surgical treatment of cryptorchidism and apply this only
      after a waiting period, and if the hormonal approach has failed to descend the
      testis.

PMID- 1356319
TI  - Lack of interaction between propofol and vecuronium.
AB  - We estimated the potency of vecuronium and measured the onset and duration of its
      action during total intravenous anesthesia with propofol to examine the
      possibility of any interaction between these two drugs. Propofol infusion was
      administered according to a three-step dosage scheme, and neuromuscular block was
      monitored by measuring the force of contraction of the adductor pollicis muscle
      after single-twitch stimulation of the ulnar nerve at 0.1 Hz. A control group of
      patients were similarly studied during anesthesia with thiopental, nitrous oxide,
      oxygen, and fentanyl. The ED50 and ED95 (dose required to produce a 50% and 95%
      depression of twitch tension, respectively) of vecuronium in patients given total
      intravenous anesthesia (n = 24) were 24 (22-27, 95% confidence limits) and 41 (37
      48, 95% confidence limits) micrograms/kg, respectively, and in the control group
      (n = 24), 20 (17-24) and 39 (34-37) micrograms/kg, respectively. The onset of
      action of an 80-micrograms/kg dose (2 x ED95) of vecuronium was 3.6 +/- 1.2 and
      4.1 +/- 1.7 min (mean +/- SD), in the propofol (n = 10) and control (n = 10)
      groups, respectively. The respective times to recovery of the twitch height to
      25% of control and the recovery indices (25%-75% recovery of twitch height) in
      the propofol versus control groups were 28.3 +/- 6.6 and 28.0 +/- 1.7 min and
      13.3 +/- 6.8 and 15.4 +/- 11.9 min, respectively. There were no significant
      differences in any of the measured variables between the propofol and control
      groups, indicating the lack of any interaction between propofol and vecuronium.

PMID- 1356320
TI  - Intraoperative monitoring of tibialis anterior muscle motor evoked responses to
      transcranial electrical stimulation during partial neuromuscular blockade.
AB  - We studied the feasibility of recording motor evoked responses to transcranial
      electrical stimulation (tce-MERs) during partial neuromuscular blockade (NMB). In
      11 patients, compound muscle action potentials were recorded from the tibialis
      anterior muscle in response to transcranial electrical stimulation during various
      levels of vecuronium-induced NMB. The level of NMB was assessed by accelerometry
      of the adductor pollicis muscle after train-of-four stimulation of the ulnar
      nerve. The compound muscle action potential was also recorded from the tibialis
      anterior muscle after direct stimulation of the peroneal nerve (M-response) as an
      alternative means of assessing the degree of NMB. In all patients, tce-MERs could
      be recorded reliably during anesthesia with N2O and a continuous infusion of
      sufentanil (0.5 micrograms.kg-1.h-1). An intact train-of-four was present in all
      patients, and the amplitude of the first twitch was recorded and designated as
      the control value. Before administration of vecuronium, the M-response amplitude
      was 9.6 +/- 3.6 (mean +/- SD) mV, and the tce-MER amplitude was 1.21 +/- 0.66 mV.
      Although administration of vecuronium (0.05 mg/kg) resulted in loss of the
      mechanical adductor pollicis response in 8 of the 11 patients, the M-response and
      the tce-MER remained recordable. Subsequently, during an infusion of vecuronium,
      adjusted to maintain one or two mechanical responses to train-of-four
      stimulation, the average M-response to peroneal nerve stimulation was 5.2 +/- 2.5
      mV (53% of the control value), and tce-MER amplitude was 0.59 +/- 0.36 mV (59% of
      the control value).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356321
TI  - [Insect repellents].

PMID- 1356322
TI  - [Portal blood levels of mitomycin C after intraperitoneal administration].
AB  - Portal blood levels of mitomycin C (MMC) were measured after intraperitoneal
      administration of 10 or 20 mg of mitomycin C following pancreatoduodenectomy. The
      portal concentration of MMC increased rapidly to the maximum concentration of 826
      +/- 364 ng/ml at 5 minutes after administration, when the dosage was 20 mg (four
      cases). The peripheral blood levels followed the portal levels and the maximum
      concentration was 397 +/- 123 ng/ml at 15 minutes. Then the MMC levels of both
      portal and peripheral blood decreased gradually, but concentration higher than
      100 ng/ml was maintained for 90 minutes after administration. In four patients
      given 10 mg of MMC, the patterns of the blood levels were similar, but the
      concentration was lower than in the group given 20 mg. In both groups, the AUC
      values were higher in portal than in peripheral blood. MMC administered
      intraperitoneally was absorbed rapidly through portal circulation and a high MMC
      level of portal blood was obtained. Therefore, it would prevent the dissemination
      of cancer cells into the liver which may well occur during operation for
      pancreatic carcinoma.

PMID- 1356323
TI  - Neurohumoral changes and the inducibility of ventricular tachycardias: effect of
      early reperfusion on the ischemic porcine myocardium.
AB  - The effects of early reperfusion were studied in closed-chest pigs subjected to
      either 45 min or 3 hr of regional ischemia. Myocardial enzyme release during
      early reperfusion and electrophysiological stability after two weeks were
      assessed. Coronary artery occlusion durations of 3 hr and early reperfusion after
      45 min were compared. The creatine phosphokinase levels in the coronary effluent
      were lower after early reperfusion (p less than 0.001). Moreover, in the early
      reperfusion group, the coronary sinus catecholamine and purine levels rose to
      higher values than in the 3 hr group. The plasma levels of catecholamines and the
      plasma renin activity increased rapidly but transiently at reperfusion in the 45
      min group. Both the rate-pressure product and the heart rate were elevated at the
      end of the reperfusion period (p less than 0.001) in the 45 min group. Survival
      for two weeks was 3 out of 6 animals in the 3 hr group and 5 out of 8 in the 45
      min group. In all but one surviving animal, sustained ventricular tachycardias
      were inducible by programmed stimulation. Abnormally low QRS amplitudes and
      delayed potentials were found in the signal-averaged electrocardiogram in the
      early reperfusion group only. In conclusion, early reperfusion causes a reduction
      of myocardial tissue damage, but simultaneously, neurohumoral parameters showed a
      greater activation of the sympathetic nervous system and the renin-angiotensin
      system apparently causing a deleterious increase in oxygen consumption.
      Therefore, this injurious component of early reperfusion might prevent the
      potentially beneficial effects of a reduced tissue damage on survival or late
      arrhythmias.

PMID- 1356324
TI  - The pharmacology of 1-phenyl-2-propylamino-pentane (PPAP), a deprenyl-derived new
      spectrum psychostimulant.
AB  - The peculiar tyramine uptake inhibitory effect of (-)deprenyl prompted structure
      activity relationship studies aiming to develop new spectrum central nervous
      system stimulants which are devoid of MAO inhibitory potency and operate de facto
      as indirectly acting, nonreleasing sympathomimetics. Of the derivatives
      synthesized for this purpose, 1-phenyl-2-propylaminopentane (PPAP) was selected
      as the reference substance and its pharmacological spectrum is presented. PPAP is
      taken up by the catecholamine axon terminal membrane and the vesicular membrane
      but it is devoid of catecholamine-releasing property. As a result, PPAP is, by
      interference, a potent inhibitor of the uptake of indirectly acting
      sympathomimetic releasers and of the catecholamine transmitters. This was proved,
      on the one hand, by measuring the uptake of [14C]PPAP into the catecholaminergic
      axon terminals and the inhibition of the uptake of [3H]noradrenaline and
      [3H]dopamine by PPAP in the rat brain, and, on the other hand, on the pulmonary
      artery strip of the rabbit and, in vivo, using the rat nictitating membrane as a
      detector. PPAP increases motility at 2 mg/kg and, in contrast to amphetamine,
      inhibits it at very high doses (50 mg/kg) only. A two-sided antagonism in the
      motility-increasing effect between PPAP and amphetamine and, more pronounced,
      between PPAP and mazindol was detected. PPAP is substantially less effective in
      inducing stereotyped behavior than either amphetamine or methamphetamine. PPAP
      facilitates learning and retention, is highly potent in antagonizing the
      tetrabenazine-induced depression in behavioral tests and is very effective in the
      forced swimming test. Whereas amphetamines facilitate performance in a very
      narrow range of low doses, which turns, at a modest elevation of the dose, into
      the opposite effect, PPAP improves performance within a reasonably broad dose
      range. Based on the peculiar pharmacological profile of PPAP, its potential
      usefulness in depression, in Alzheimer's disease and in attention-deficit
      hyperkinetic disorder seems to be plausible.

PMID- 1356325
TI  - Dopamine-induced contractile responses of the rat anococcygeus muscle.
AB  - In the rat anococcygeus muscle both dopamine and noradrenaline induced
      concentration-dependent contractile responses. The alpha 1-antagonist prazosin
      inhibited both dopamine and noradrenaline responses, whereas the alpha 2
      antagonist yohimbine influenced noradrenaline-mediated responses only. The
      concentration-effect curves for dopamine were shifted to the right in presence of
      cocaine or after treatment with reserpine and alpha-methyl-p-tyrosine. When the
      tissues were previously exposed to 6-hydroxydopamine, the tyramine-induced
      contractile effect was abolished. Dopamine-induced concentration-effect curves
      were markedly shifted to the right. Treatment with 6-hydroxydopamine and
      reserpine did not modify the concentration-effect curves to noradrenaline. Our
      results indicate that dopamine has a dual effect: a partial effect due to an
      indirect sympathomimetic action and a partial effect due to the interaction with
      postjunctional receptors.

PMID- 1356326
TI  - [Rhythmogenic cardiomyopathies of atrial origin in children. Myth or reality?].
AB  - Incessant, rapid, supraventricular tachycardia may be complicated by cardiac
      failure with ventricular dilatation and hypokinetic wall motion on
      echocardiography: so-called tachycardia-induced cardiomyopathy. The diagnosis is
      simple when the cardiac rhythm is not sinus rhythm. The authors report the cases
      of 4 children aged 7 months to 12 years, referred for diagnosis and treatment of
      apparently primary cardiomyopathy. The findings of spontaneous or vagally-induced
      atrioventricular conduction defects, a permanently rapid atrial rhythm though
      influenced by 24 hour variations, or periodic abnormal rate increases, suggested
      myocardial dysfunction due to an ectopic atrial tachycardia. This was an
      essential step in management as the control of the tachycardia by amiodarone or
      betablocker therapy resulted in regression of symptoms and normalisation of left
      ventricular function. However, some atrial tachycardias are very resistant to
      medical treatment and, in such cases, there should be no hesitation in using more
      radical approaches, surgery or ablation, even and especially in patients with
      severe cardiac failure. In conclusion, apparently primary dilated cardiomyopathy
      in children may be due to chronic atrial arrhythmia and it is essential to
      perform at least Holter monitoring in order not to miss this diagnosis.

PMID- 1356328
TI  - [Electric stability of the heart after myocardial infarction: role of anti
      arrhythmia agents during postinfarction].
AB  - Electrical instability of the heart after myocardial infarction threatens
      surviving patients with sudden death from a severe ventricular arrhythmia. These
      arrhythmic complications are usually the result of several factors: an
      arrhythmogenic substrate corresponding to the ischaemic myocardium, a trigger
      factor (usually a ventricular extrasystole) and other predisposing factors
      (autonomic nervous system, electrolyte imbalance, activation of the renin
      angiotensin system). Risk stratification of electrical instability combines
      noninvasive (Holter, exercise testing, signal averaged electrocardiography, study
      of the variability of the heart rate, radionuclide or echocardiographic
      evaluation of the left ventricular ejection fraction) and invasive investigations
      (coronary angiography and even programmed ventricular stimulation). The presence
      of late ventricular potentials, a low ejection fraction and/or a ventricular
      arrhythmia on Holter monitoring identifies a high risk subgroup. Although the
      assessment of electrical instability is better than it used to be,
      pharmacological prevention remains disappointing. Class I antiarrhythmics are
      ineffective or dangerous. The efficacy of Class III antiarrhythmics is uncertain
      and only the betablockers seem to have any beneficial effects on this post
      infarction electrical instability.

PMID- 1356327
TI  - [Drug therapy of acute myocardial infarction without cardiogenic shock and
      thrombolytic therapy excluded].
AB  - Myocardial infarction is responsible for 25,000 deaths per year in France and is
      a real problem of public health. The management of patients victims of this
      condition is an important feature of medical practice. Thrombolytic therapy has
      resulted in significant improvements in the reduction of the size of the infarct,
      in the conservation of left ventricular function and in the reduction of
      mortality. Treatment of the acute phase of myocardial infarction, especially when
      there are contra-indications to thrombolysis, comprises other approaches, some of
      which are old, which are reviewed in the light of the results of the latest large
      scale therapeutic trials.

PMID- 1356329
TI  - [Nitrate derivatives, current pharmacological and clinical status. Seville, 24-28
      October 1991].

PMID- 1356330
TI  - [Isosorbide dinitrate in the treatment of coronary insufficiency].
AB  - The improvement of our understanding of the pharmacology of nitrate derivatives
      has allowed rationalisation of their use in the treatment of coronary artery
      disease. The comprehension of the evolution of the sensitivity of the vessel wall
      to nitrate vasodilatation with time has enabled definition of a rhythm of
      administration which preserves therapeutic efficacy: a daily therapeutic window
      of 8 to 10 hours. The introduction of new galenic forms (slow release oral
      preparations and transdermal patches) facilitates the practical application of
      the "optimal" pharmacokinetic profile. A single daily dose of slow release ISDN
      is effective in controlled trials versus placebo in the treatment of chronic
      stable angina. Many clinical trials have also shown the synergy of the anti
      anginal effects of ISDN and betablockers, both in single dose studies and during
      prolonged administration. These therapeutic windows are not adapted to the
      treatment of acute coronary insufficiency (unstable angina, myocardial
      infarction); however, it has recently been shown that the use of small, fixed
      doses of intravenous ISDN over a 3 day period is usually adequate for controlling
      acute coronary insufficiency and is not associated with the phenomenon of
      tolerance.

PMID- 1356331
TI  - Recent advance in the treatment of PTSD.

PMID- 1356332
TI  - Sumatriptan and other drugs used in migraine treatment.

PMID- 1356333
TI  - Studies on the active centre of Rhodotorula gracilis D-amino acid oxidase and
      comparison with pig kidney enzyme.
AB  - D-Amino acid oxidase (EC 1.4.3.3) from Rhodotorula gracilis has been
      reconstituted with 8-chloro-, 8-mercapto-, 6-hydroxy-, 2-thio-, 5-deaza- and 1
      deaza-FAD, and the properties of the resulting complexes have been studied and
      compared with those of the correspondingly modified pig kidney D-amino acid
      oxidases. Binding appears to be tight for most analogues, at least as tight as
      for native FAD (approximately 10(-8) M). 8-Mercapto- and 6-hydroxy-FAD bind in
      their para- and ortho-quinoid forms respectively to yeast D-amino acid oxidase,
      inferring the presence of a positive charge near the flavin N(1) position, as in
      the case of the mammalian enzyme. On the other hand, important differences in
      active-site microenvironment emerge: solvent accessibility to flavin position 8
      is drastically restricted in yeast D-amino acid oxidase as indicated by the
      unreactivity of 8-chloro- and 8-mercapto-FAD enzyme with thiolates and alkylating
      agents. Significantly different microenvironments are also likely to occur around
      the flavin positions N(1)-C(2) = 0, N(3)-H and N(5). This is deduced from the
      differences in interaction of the two proteins with 1-deaza-FAD, 5-deaza-FAD and
      2-thio-FAD and from the properties of the respective complexes. The same re-side
      flavin stereospecificity as shown by the mammalian enzyme was determined for the
      yeast enzyme using 8-hydroxy-5-deaza-FAD. Thus we can deduce the presence of a
      similar pattern of functional groups at the active centres of the two enzymes,
      while the fine tuning of specificity and regulation correlate with environmental
      differences at specific flavin loci.

PMID- 1356334
TI  - Effectors of ATP-sensitive K+ channels inhibit the regulatory effects of
      somatostatin and GH-releasing factor on growth hormone secretion.
AB  - Somatostatin inhibition of growth hormone (GH) secretion from adenohypophysis
      cells in culture was antagonized by the antidiabetic sulfonylurea glipizide (K0.5
      = 10 +/- 5 nM). Although all cells that hyperpolarize with somatostatin have ATP
      sensitive K+ channels, the antagonistic actions of the hormone and of the
      antidiabetic drug are due to effects on different types of K+ channels.
      Diazoxide, an opener of ATP-sensitive K+ channels, abolished the increase of
      intracellular Ca2+ provoked by growth hormone releasing factor (GRF) and induced
      inhibition of GRF stimulated GH secretion (K0.5 = 138 microM). This inhibition by
      diazoxide was largely suppressed by glipizide which blocked the ATP-sensitive K+
      channels opened by diazoxide. In summary, hormonal activation of GH secretion is
      inhibited by openers of ATP-sensitive K+ channels, while hormonal inhibition of
      GH secretion is suppressed by blockers of ATP-sensitive K+ channels.

PMID- 1356335
TI  - Effect of liposomes on P-glycoprotein function in multidrug resistant cells.
AB  - Presentation of doxorubicin in liposomes has shown to enhance the sensitivity of
      multidrug resistant CH LZ cells to the drug (Thierry et al. Cancer Commun. 1:311
      316, 1989). We confirmed that liposomally encapsulated doxorubicin may partially
      overcome multidrug resistance in the human ovarian carcinoma SKVLB cell line and
      that this effect is, at least in part, due to an increase of cellular drug
      accumulation. When used at high concentration, empty liposomes appear to be
      specifically cytotoxic in the MDR SKVLB and CH LZ cells. As observed with certain
      multidrug resistance modulators, empty liposomes inhibited the specific [3H]
      vincristine binding to P-glycoprotein-enriched membranes isolated from CH LZ
      cells (60% at 0.2 mg lipid/ml). Our data suggest that liposomes may alter the P
      glycoprotein function by direct interaction.

PMID- 1356336
TI  - Activation of human multidrug resistance-1 gene promoter in response to heat
      shock stress.
AB  - The multidrug resistance (MDR1) gene encodes a P-glycoprotein, which catalyzes
      the energy-dependent efflux of anticancer agents. Various environmental stresses
      including heat shock can induce the expression of endogenous MDR1 genes. In order
      to study the regulatory mechanisms of MDR1 gene expression, we have established
      human cancer KB cell lines which could stably integrate bacterial chloramphenicol
      acetyltransferase (CAT) gene driven by various lengths of the MDR1 promoter. Kst
      6 has an integrated plasmid, pMDRCAT1, containing the human MDR1 promoter of -2
      kilobases. The MDR1 gene promoter contains a typical heat shock element (HSE)
      motif located -152 bp to -178 bp from the initiation site. Heat shock at 45
      degrees C for 90 min significantly induced CAT activity in Kst-6 cells. Northern
      blot analysis showed a 4-5 fold increase in CAT mRNA levels in Kst-6 cells.
      Deletion analysis of the MDR1 promoter demonstrated that the induction of CAT
      activity was observed in Kxh-14 cells containing a HSE-deleted MDR1 promoter
      construct, pMDRCAT7. However, further deletion analysis showed that heat shock
      could not induce CAT activity in Khp-1 cells containing -76 approximately +121
      base sequence of the promoter, suggesting that a new heat shock responsible
      element was located at between -136 and -76. Gel shift assay showed that the heat
      shock factor (HSF) could bind to the HSE motif located at -152 bp to -178 bp in
      the MDR1 promoter. We also found that one distinct DNA-protein complex formed
      specifically within the MDR1 promoter region -99 to -66 was not significantly
      increased, but relatively more stabilized under mild denaturing condition in the
      nuclear extract of heat-shocked cells. In our present assay system, activation of
      the MDR1 promoter in response to heat shock appears to be mediated through both a
      new heat shock responsive element and MDR1 specific transcription factor.

PMID- 1356337
TI  - de novo biosynthesis of heme offers a new chemotherapeutic target in the human
      malarial parasite.
AB  - The human malarial parasite, Plasmodium falciparum, has been found to synthesize
      heme de novo, despite the accumulation of large quantities of polymeric heme
      derived from the hemoglobin of the red cell host. The parasite delta
      aminolevulinate dehydrase level is significantly lower than that of the host and
      its inhibition by succinylacetone leads to inhibition of parasite protein
      synthesis and viability.

PMID- 1356338
TI  - Insulin-responsive tyrosine aminotransferase transcription requires multiple
      promoter regions.
AB  - This study used transient transfection analysis to determine the DNA regions
      which mediate basal and insulin-sensitive transcription from the gene encoding
      tyrosine aminotransferase (TAT; EC 2.6.1.5). Basal expression requires at least
      parts of two regions: a region at -3600 and a region from -208 to + 62. Insulin
      sensitivity requires at least one region of the promoter not required for basal
      expression. Thus, insulin cannot act solely by direct modification of any of the
      components required for basal transcription. Previous results from this
      laboratory suggest that the insulin effects on basal and glucocorticoid-induced
      TAT transcription require different regions of the proximal promoter.

PMID- 1356339
TI  - Overexpression of P-glycoprotein and alterations in topoisomerase II in P388
      mouse leukemia cells selected in vivo for resistance to mitoxantrone.
AB  - The overexpression of P-glycoprotein (PGP) and alterations in DNA topoisomerase
      II (TOPO II) were evaluated in mouse leukemia P388 cells selected in vivo for
      mitoxantrone (MTT) resistance (P388/MTT) and compared to doxorubicin (DOX)
      resistant (P388/DOX) or vincristine (VCR) resistant (P388/VCR) models. Among a
      panel of TOPO II inhibitors which included etoposide (VP-16), DOX, MTT and 4'-[(9
      acridinyl)-amino]methanesulfon-m-anisidide (m-AMSA), the relative resistance
      compared to parental sensitive P388/S cells was: P388/DOX greater than P388/MTT
      greater than P388/VCR. All the resistant sublines exhibited minimal cell kill
      (less than 20%) at vincristine concentrations greater than 100-fold the IC50 for
      P388/S cells. In a soft-agar colony-forming assay, the modulation of cytotoxicity
      in P388/MTT cells by the calmodulin inhibitor trifluoperazine following a 3-hr
      drug treatment demonstrated a marked potentiation in cell kill with MTT, VP-16,
      DOX and m-AMSA but not VCR. Immunoblotting data revealed that while PGP was not
      detectable in P388/S cells, the overexpression of PGP was apparent in P388/MTT
      cells and the relative expression between the resistant sublines was: P388/DOX
      greater than P388/MTT greater than P388/VCR. Although the amount and DNA cleavage
      activity of TOPO II in nuclear extracts from P388/VCR cells were comparable to
      those in P388/S cells, they were markedly lower in both P388/DOX and P388/MTT
      cells. However, decatenation activity of TOPO II in nuclear extracts was
      comparable between the sensitive (P388/S) and resistant sublines (P388/MTT,
      P388/DOX, and P388/VCR). Results from the present study demonstrated that P388
      cells selected for resistance to mitoxantrone exhibit changes in TOPO II and
      overexpression of PGP similar to P388/DOX cells, while vincristine resistant
      cells only overexpress PGP. Since therapeutic strategies are primarily designed
      to interfere with PGP-mediated drug efflux, the choice of agents for modulating
      resistance in tumors which overexpress PGP versus tumors which overexpress PGP
      with altered TOPO II could be different.

PMID- 1356341
TI  - Research in Medical Education. Proceedings of the 31st annual conference. New
      Orleans, Louisiana, November 1992.

PMID- 1356340
TI  - Postreceptor modulation of cAMP accumulation in rat brain particulate fraction
      after ischemia--involvement of protein kinase C.
AB  - The brain cyclic AMP generation was studied in rats subjected to 15 min of
      cardiac arrest. We have used a particulate, synaptoneurosomal fraction to
      demonstrate the effect of ischemia in vivo on the responsiveness of adenylate
      cyclase (AC) system. It has been shown that, although there is a slight decrease
      in AC activity after ischemia, the in vitro fractions produce more cAMP in
      response to a variety of stimuli, suggesting an indirect, nonadenylate cyclase
      activation mechanism. For elucidation of this mechanism we have probed phorbol
      12,13-dibutyrate (PDBu) as a direct PKC activator, forskolin to activate the
      catalytic subunit of AC, and cholera toxin (CT) for stabilizing the active, GTP
      bound form of stimulatory guanine nucleotide binding protein (Gs). All these
      postreceptor AC modulators as well as the receptor activators such as adenosine
      and alpha 1-adrenergic agonists markedly enhanced cAMP production in the rat
      brain particulate fraction, although the postischemic hyperactive response to
      these stimuli was still present. However, when AC was stimulated by the
      combination of CT and PDBu, cAMP responses were identical in both control and
      postischemic fractions. The data, taken together, support the hypothesis that
      ischemia increases cAMP accumulation by facilitating the postreceptor AC
      activation through a PKC-involving pathway and by promoting the stronger coupling
      of membrane AC receptors with G-protein. Protein kinase C (PKC) activity during
      cerebral ischemia was also investigated. In contradistinction to our expectation
      PKC decreased significantly in the ischemic brain to 85% of the control activity
      in the cytosol and 72% in the membranes. However, in the incubated post-ischemic
      brain particulate fraction a relative increase in the membrane-bound form of the
      enzyme, from 30% for control to 53% for ischemia, was observed. This may suggest
      that ischemia-induced membrane changes could promote the enzyme
      translocation/activation during recovery, resulting in the sensitization of cAMP
      producing system.

PMID- 1356342
TI  - Structural studies on H2-antagonists: crystal and molecular structure of N-cyano
      N'-methyl-N"-(2-[(2-amino-5-thiazolyl)methylthio]ethyl) guanidine and N-cyano-3
      [(2-guanidino-5-thiazolyl)methylthio]propionamidine.
AB  - The crystal and molecular structures of N-cyano-N'-methyl-N"-(2-[(2-amino-5
      thiazolyl) methylthio] ethyl) guanidine and N-cyano-3-[(2-guanidino-5
      thiazolyl)methylthio]propionamidine are reported. Both molecules are in an
      extended conformation. In all two crystals a system of hydrogen bonds links the
      molecules in a three-dimensional network. A comparison with the structure of
      cimetidine and famotidine is also included.

PMID- 1356343
TI  - Autoimmunity--towards the year 2001.
AB  - The interactive roles of T cells, major histocompatibility complex (MHC) class I
      and II molecules and antigen-presenting cells in the generation of autoimmunity
      is the subject of much discussion. A recent symposium contributed to the debate
      by inviting experts in several fields of immunology to answer specific questions
      relating to the mechanisms that trigger autoimmunity.

PMID- 1356345
TI  - The macrophage 1992. European conference on basic and clinical aspects of
      macrophage biology. Regensburg, FRG, September 20-22, 1992. Abstracts.

PMID- 1356344
TI  - Alterations in the structural gene and the expression of p53 in rat liver tumors
      induced by aflatoxin B1.
AB  - Rat hepatocellular carcinomas (HCCs) induced by aflatoxin B1 (AFB) treatment were
      examined for changes in the p53 tumor suppressor gene and in p53 suppressor gene
      expression. A high proportion of HCCs (nine of 11 tumors in six of eight animals)
      exhibited new p53 restriction fragments, indicating genomic alterations of one of
      the p53 alleles. Each tumor with an altered p53 restriction-fragment pattern
      exhibited a new fragment in one of two size classes (3 kb or 7 kb with EcoRI
      digestion) that were missing portions of the 3' end of the p53 gene. These
      findings indicate that apparently similar genomic rearrangements or deletions
      occurred independently in AFB-induced tumors. When compared with nontumor liver
      tissue from the same animal, the tumors with p53 gene alterations showed
      dramatically reduced levels of p53 mRNA and protein and greatly increased levels
      of histone H2B and retinoblastoma tumor suppressor (Rb) mRNA. In two HCCs showing
      no evidence of p53 restriction-fragment alterations, mutant p53 protein was
      detected. Mutant protein was also detected in two liver samples containing an
      adenoma and altered foci. These data suggest that alterations of the p53 tumor
      suppressor gene are involved in the induction of rat HCC by AFB.

PMID- 1356347
TI  - How human immunodeficiency virus ravages the immune system.
AB  - The immune system of individuals infected with human immunodeficiency virus is
      affected in two distinct ways: by loss of CD4+ cells and by loss of T-helper-cell
      function. Neither of these processes is yet fully understood. Research during
      1991 that investigated the interaction between human immunodeficiency virus and
      the immune system has raised as many questions as it answered. Nevertheless, many
      of the issues raised are relevant to mechanisms responsible for the ravaging of
      the immune system by human immunodeficiency virus.

PMID- 1356346
TI  - Immunology of leishmaniasis.
AB  - Resolution of leishmanial infections requires the expansion of specific type 1 T
      helper cells that secrete or express on their membrane lymphokines capable of
      activating macrophages that contain these parasites to a microbicidal state.
      Specific CD8+ T cells, which are triggered during infection, also appear to play
      a role in protective immunity, possibly through their ability to secrete
      interferon-gamma. In the mouse model of infection with Leishmania major, the
      expansion of specific type 2 T helper cells exacerbates disease, an effect that
      appears to result from the properties of type 2 T helper derived lymphokines to
      deactivate macrophages and inhibit release of activating cytokines by type 1 T
      helper cells. In the mouse, destruction of intracellular Leishmania by activated
      macrophages depends upon the L-arginine-dependent production of nitrogen oxides.
      Molecules from the parasite that can induce, and are the target of, the
      protective T-cell response are being characterized.

PMID- 1356348
TI  - Molecular insights into human immunodeficiency virus type 1 pathogenesis.
AB  - Infection with human immunodeficiency virus type 1 leads to a persistent but
      progressive cytopathic process that culminates in the near complete destruction
      of the CD4+ subset of T cells. The levels of human immunodeficiency virus type 1
      replication and virus burden increase throughout the clinical course of disease
      reflecting a balance between the viral and cellular regulatory influences as well
      as the ability of the host immune system to eliminate infected T cells. Human
      immunodeficiency virus type 1 replication is dependent on the state of cellular
      activation and involves both inducible host cell derived transcription factors
      and at least three virus-derived gene products. Further study of the mechanism of
      action of these factors, particularly those encoded by the virus, may facilitate
      the future development of highly specific and effective therapies for human
      immunodeficiency virus type 1.

PMID- 1356349
TI  - Animal models for the study of human immunodeficiency virus infections.
AB  - Recent studies in animal models have advanced our understanding of determinants
      of acquired immune deficiency syndrome pathogenesis. They have also indicated the
      potential importance of both the envelope glycoprotein of the virus that causes
      acquired immune deficiency syndrome and cell surface molecules in vaccine
      elicited protective immunity.

PMID- 1356350
TI  - Current status of therapy for human immunodeficiency virus type 1.
AB  - The past year has been refinement in our ability to delay the progression of
      human immunodeficiency virus type 1 infection through the use of nucleoside
      analogues, singly or in combination. Progress has also been made in our ability
      to detect drug-resistant isolates of human immunodeficiency virus type 1 and to
      begin to put the laboratory observations of resistance into a clinical context.

PMID- 1356351
TI  - Periodontal disease in HIV-infected and uninfected homosexual and bisexual men.

PMID- 1356352
TI  - Cognition and immune function in HIV-1 infection.
AB  - OBJECTIVES: To determine (1) whether there were differences in cognition between
      HIV-1-seropositive and HIV-1-seronegative homosexual men and (2), if so, whether
      these differences could be explained by the degree of immunosuppression [i.e.,
      CD4 cell count and immunoglobulin A (IgA) levels]. DESIGN: A cross-sectional
      design was used to compare 66 HIV-1-seropositives (Centers for Disease Control
      stages II and III, n = 56; stages IVA and IVC-2, n = 10) and 37 HIV-1
      seronegatives. The HIV-1-seropositives were classified into three immune groups
      based on their CD4 cell count (x 10(6)/l) and serum IgA level (mg/dl): (1)
      moderate [(n = 35) CD4 greater than 400, IgA less than 300]; (2) mixed [(n = 22)
      either CD4 greater than 400 and IgA greater than 300 or CD4 less than 400 and IgA
      less than 300] and (3) poor [(n = 9) CD4 less than 400, IgA greater than 300].
      HIV-1-seronegatives formed the 'good' immune group (CD4 greater than 400 and IgA
      less than 300). METHODS: The four groups were compared on tests of verbal and
      visual memory, information-processing speeds, visuospatial skills, language
      processes, attention, psychomotor reaction time, and mental status. Factors other
      than HIV-1 sero-status that can influence cognitive performance were tested as
      covariates. RESULTS: HIV-1-seropositives had slower information-processing speeds
      and decreased verbal and visual memory, compared with HIV-1-seronegatives. These
      differences in cognition were not due to differential immunosuppression or to
      clinical status among the HIV-1-seropositives. CONCLUSIONS: Cognitive alterations
      occur in HIV-1-infected individuals before AIDS and appear to be independent of
      clinical status and degree of immunosuppression as measured by CD4 cell count and
      IgA levels.

PMID- 1356353
TI  - Abstracts of the Nordic Symposium: Mental Retardation in Childhood. Oslo,
      February 13-15, 1992.

PMID- 1356354
TI  - In vitro effects of putative neurotransmitters on synaptic ribbon numbers and N
      acetyltransferase activity in the rat pineal gland.
AB  - The pineal contains a large number of classical transmitters and neuropeptides.
      Some of these neurochemicals are involved in the regulation of serotonin N
      acetyltransferase (NAT) activity and hence in melatonin synthesis. Synaptic
      ribbons present in the pineal gland also exhibit a numerical day/night rhythm
      parallel to that of NAT activity. There is scarcity of information regarding the
      regulation of synaptic ribbon (SR) numbers. In the present study, we have
      investigated in vitro effects of a number of classical neurotransmitters and
      neuropeptides. NAT activity was used to monitor melatonin synthesis under the
      experimental conditions used. Norepinephrine (NE), Delta sleep-inducing peptide
      (DSIP), vasoactive intestinal polypeptide (VIP), adenosine and N-acetyl-asp-glu
      (NAAG) significantly increased NAT activity in rat pineal. DSIP and VIP also
      increase the stimulatory effect of NE on NAT activity. These neurochemicals had
      no effect on SR numbers. Gamma aminobutyric acid (GABA), serotonin and taurine
      affected neither NAT activity nor SR. Somatostatin increased SR numbers
      significantly, without having any effect on NAT activity. The effect of
      somatostatin is regarded to be pharmacologic, since rather high dosages (10(-4)
      M) were required to obtain a significant effect. Although somatostatin is present
      in the pineal and may change rhythmically, the inconsistency of the day/night
      rhythmicity and the lack of such a rhythm in female rats and male gerbils speaks
      against an important physiological role of somatostatin in regulating SR numbers.

PMID- 1356355
TI  - Glucocorticoids, transmitters and stress.
AB  - Many kinds of stress stimulate the neuroendocrine systems controlling
      catecholamine and glucocorticoid secretion. Stress-induced stimulation of CRF
      containing neurons appears to be mediated by serotonergic, noradrenergic, and
      possibly other neuronal pathways. Stress can alter various neurobiological and
      endocrine functions, two essential components of the neuroendocrine responses
      being release of adrenalin from chromaffin cells of the adrenal medulla and
      secretion of glucocorticoids from adrenocortical cells. Activation of adrenal
      steroid secretion is mainly by a reflex activation of hypothalamic neurons, which
      stimulate ACTH secretion from the anterior pituitary. While the neuropeptide CRF
      plays a major role in the neuroendocrine response to stress, the neuronal signals
      which are responsible for the regulation of CRF neurons have not been completely
      elucidated. A number of other regulatory substances may also participate, alone
      or with CRF, in the control of ACTH secretion by pituitary corticotrophs, and
      there is increasing evidence that classical neurotransmitters or neuropeptides
      may act directly on adrenocortical cells to modulate corticosteroid secretion. We
      review the neuronal, neuroendocrine, and humoral pathways which participate in
      the regulation of stress-induced corticosteroid secretion, and present
      preliminary data on the effect of the tricyclic antidepressant, tianeptine in the
      response of the HPA axis to stress.

PMID- 1356356
TI  - Depression as a consequence of inadequate neurochemical adaptation in response to
      stressors.
AB  - Stressors induce behavioural disturbances and neurochemical changes in animals,
      some of which are reminiscent of the symptoms and presumed neurochemical
      concomitants of depression in humans. Just as in humans, where considerable inter
      individual variability is evident in the symptom profile of depression, there is
      marked inter-individual and inter-strain variability in the behavioural effects
      of stressors in animals. It is proposed that stressors induce adaptive
      neurochemical changes, failure of which may engender behavioural disturbances.
      Variability in the symptoms of depression and in the efficacy of its
      pharmacological treatment may reflect the biochemical heterogeneity of the
      illness. Inter-individual differences in vulnerability to stressor-provoked
      neurochemical changes may contribute to the behavioural profiles observed.

PMID- 1356357
TI  - Animal behavioural studies in the evaluation of antidepressant drugs.
AB  - Animal behavioural models of psychiatric disorders cannot exactly simulate human
      psychopathology, but they can be used to evaluate the behavioural changes induced
      by drugs and to suggest hypotheses about the functions of the CNS and its
      involvement in psychiatric disorders. This should lead to a more heuristic
      classification of psychotropic drugs and to clarification of their therapeutic
      possibilities. The following animal models simulate aspects of depressive
      disorders and are sensitive to the antidepressant effects of drugs. (i) The
      forced swimming test: described as 'behavioural despair' on the assumption that
      the animal has given up hope of escaping. (ii) The 'restraint stress' test: this
      may indicate a failure to adapt to stress. (iii) The learned-helplessness model:
      exposed to uncontrollable events, animals exhibit learning performance deficit
      and behavioural changes, including decreased locomotor activity and loss of
      appetite. (iv) Waiting behaviour: improvement in the ability to wait for and/or
      postpone an active response; this could be related to the reported beneficial
      effects of antidepressants on impulsive behaviour.

PMID- 1356358
TI  - The effects of tianeptine and other antidepressants on a rat model of depression.
AB  - A model of depression based on measurements made after restraining rats for two
      hours has been developed. The model is associated with elevation in
      corticosterone, reflects the higher incidence of depression in women, and shows
      increased post-synaptic 5-HT function with adaptation. The effects of tianeptine
      and other antidepressants on the model were studied. Chronic pre-treatment with
      desipramine, sertraline (amine uptake inhibitors), and chlordiazepoxide
      normalised open field activity after restraint. Single high doses, post
      restraint, of 8-OH-DPAT, gepirone (5-HT agonists), and tianeptine normalised open
      field activity, whereas desipramine, chlordiazepoxide, and diazepam did not. It
      is of considerable interest that tianeptine decreased the availability of 5-HT to
      receptors.

PMID- 1356359
TI  - Stress, Serotonin and Tianeptine. Symposium at the 8th World Congress of
      Psychiatry. Athens.

PMID- 1356361
TI  - Onset and course of schizophrenic disorders. Dynamic interactions between
      relevant factors. 3rd International Symposium on Transactional Processes in the
      Development and Course of Schizophrenic Disorders. Bern, October 1990.

PMID- 1356360
TI  - Neuroendocrine mechanisms and the precipitation of depression by life events.
AB  - It is now generally accepted that stressful life events and chronic difficulties
      can trigger the onset of depression in predisposed individuals. However, although
      much is known of the neurobiology of stress, few attempts have been made to
      provide a biological explanation for the mechanisms whereby life events might
      trigger depression. Enough is now known of the central control of hypothalamic
      pituitary adrenal (HPA) function and its response to stress to permit an
      examination of its role in the neurobiology of the triggering of depression by
      stress. This evidence is reviewed, and the proposal explored that stress triggers
      depression by a genomic action of corticosteroids.

PMID- 1356362
TI  - Vulnerability to relapse in schizophrenia.

PMID- 1356363
TI  - Ideal and reality of neuroleptic relapse prevention.

PMID- 1356364
TI  - Intermittent medication, coping and psychotherapy. Interactions in relapse
      prevention and course modification.

PMID- 1356365
TI  - The pilot project 'Soteria Berne'. Clinical experiences and results.

PMID- 1356366
TI  - Immunity against diphtheria and tetanus in human immunodeficiency virus-infected
      Danish men born 1950-59.
AB  - To evaluate the possible need for vaccination against diphtheria and tetanus of
      patients infected with the human immunodeficiency virus (HIV), antibodies were
      measured in blood samples from 78 Danish HIV-infected men, born 1950-59, who
      could be expected to have received primary vaccination before they contracted the
      HIV infection. No patients (95% confidence interval: 0-4) had tetanus antibodies
      below the protective level, whereas 24 of the 78 patients (16-33) were
      unprotected against diphtheria. In the background population of the same age
      group and sex, 5% and 10% have been found unprotected against tetanus and
      diphtheria, respectively. No relationship between disease stages and antibody
      levels could be found. Neither was there any difference between patients with
      normal and reduced numbers of CD4+ lymphocytes. From 25 patients two blood
      samples were taken at an interval of at least one year. Anti-tetanus titres
      showed a decrease comparable to that found in the background population, whereas
      the change in anti-diphtheria titres was more variable with rising antibody
      concentrations in nine patients. The fall off in antibodies did not increase with
      progression of the disease. It is concluded that HIV-positive younger men who
      have followed the vaccination program against tetanus prior to the HIV infection
      can be expected to be protected, whereas revaccination against diphtheria must be
      considered.

PMID- 1356367
TI  - Human proximal tubular cells modulate allogen responses of leukocytes in vitro.
AB  - The interaction between proximal tubular cells and leukocytes was examined. In co
      cultures of tubular cells and allogenic leukocytes, tubular cells expressed MHC
      antigens and ICAM-1. A small number of leukocytes adhered to tubular cells and
      induced cytotoxic damage. Thus, 65% of the tubular cells were viable after co
      culturing with allogenic leukocytes. These cells had low alloreactive capacity,
      which was not due to lack of interleukin-1 or interferon-gamma. The presence of
      tubular cells modulated the immune response of leukocytes by reducing the effect
      of mitogen by 80%, allogens by 65% and interleukin-2 by 40%. A soluble factor
      released in the co-cultures was a likely mediator, since addition of supernatants
      from co-cultures suppressed mitogen responses by 27% compared to leukocytes
      cultured alone. This mediator might be prostaglandin, because addition of
      indomethacin to co-cultures increased the growth response of leukocytes.

PMID- 1356368
TI  - A simple nonradioactive procedure for visualization of (dC-dA)n dinucleotide
      repeat length polymorphisms.

PMID- 1356369
TI  - Incubation with horse serum increases viability and decreases background
      neurotransmitter uptake in Xenopus oocytes.

PMID- 1356370
TI  - Constitutively active mutants of rhodopsin.
AB  - Two critical amino acids in the visual pigment rhodopsin are Lys-296, the site of
      attachment of retinal to the protein through a protonated Schiff base linkage,
      and Glu-113, the Schiff base counterion. Mutation of Lys-296 or Glu-113 results
      in constitutive activation of opsin, as assayed by its ability to activate
      transducin in the absence of added chromophore. We conclude that opsin is
      constrained to an inactive conformation by a salt bridge between Lys-296 and Glu
      113. Recently, one of the mutants, K296E, was found in a family with retinitis
      pigmentosa, suggesting that degeneration of the photoreceptor cells in
      individuals with this mutation may result from persistent stimulation of the
      phototransduction pathway.

PMID- 1356371
TI  - Molecular cloning of a retina-specific membrane guanylyl cyclase.
AB  - We have isolated and characterized cDNA clones encoding the human retinal
      guanylyl cyclase (retGC), a novel member of the membrane guanylyl cyclase gene
      family. Like other membrane guanylyl cyclases, the 1101 aa retGC is predicted to
      have a hydrophobic amino-terminal signal sequence followed by a large
      extracellular domain, a single membrane spanning domain, a kinase homology
      domain, and a guanylyl cyclase catalytic domain. In contrast to other membrane
      guanylyl cyclases, such as natriuretic peptide receptors, retGC has a relatively
      high basal level of activity when expressed in human 293 cells. cGMP production
      by retGC is unaffected by any of the known natriuretic peptides. In situ
      hybridization analysis of a variety of rhesus monkey tissues showed retGC
      transcripts to be localized exclusively along the retinal outer nuclear layer,
      corresponding to the nuclei of the rod and cone photoreceptor cells. Our results
      suggest that retGC may synthesize cGMP required for recovery of the dark state
      after phototransduction.

PMID- 1356372
TI  - Inhibitors of protein and RNA synthesis block structural changes that accompany
      long-term heterosynaptic plasticity in Aplysia.
AB  - Synaptic connections between the sensory and motor neurons of Aplysia in culture
      undergo long-term facilitation in response to serotonin (5-HT) and long-term
      depression in response to FMRFamide. These long-term functional changes are
      dependent on the synthesis of macromolecules during the period in which the
      transmitter is applied and are accompanied by structural changes. There is an
      increase and a decrease, respectively, in the number of sensory neuron
      varicosities in response to 5-HT and FMRFamide. To determine whether
      macromolecular synthesis is also required for the structural changes, we examined
      in parallel the effects of inhibitors of protein (anisomycin) or RNA (actinomycin
      D) synthesis on the structural and functional changes. We have found that
      anisomycin and actinomycin D block both the enduring alterations in varicosity
      number and the long-lasting changes in synaptic potential. These results indicate
      that macromolecular synthesis is required for expression of the long-lasting
      structural changes in the sensory cells and that this synthesis is correlated
      with the long-term functional modulation of sensorimotor synapses.

PMID- 1356374
TI  - Role of reversal agents.

PMID- 1356373
TI  - Antibodies to synaptophysin interfere with transmitter secretion at neuromuscular
      synapses.
AB  - The involvement of synaptophysin, a synaptic vesicle-specific protein, in
      transmitter release at neuromuscular synapses was studied by intracellular
      application of synaptophysin antibodies into presynaptic neurons. Polyclonal
      antibodies or their Fab fragments were loaded into spinal neurons by injection
      into one of the early blastomeres of Xenopus embryos 1 day prior to culturing or,
      alternatively, directly through a whole-cell recording pipette at the soma of
      cultured neurons. At synapses made by antibody-loaded neurons in culture, the
      spontaneous synaptic currents showed marked reduction in frequency without
      significant change in their mean amplitude. The impulse-evoked synaptic currents
      showed reduced amplitude and increased failure rate. These results suggest that
      interference with synaptophysin function by antibody binding inhibits transmitter
      secretion.

PMID- 1356375
TI  - 9th annual meeting of the Skin Pharmacology Society, Cleveland, Ohio, October 14
      16, 1992. 9th International Symposium on Bioengineering and the Skin, Sendai,
      Japan, October 19-20, 1992. Abstracts.

PMID- 1356376
TI  - The role of peroxisomes in cholesterol metabolism.
AB  - There is now considerable evidence that peroxisomes not only have a role in
      cholesterol oxidation but also in cholesterol biosynthesis. Specifically,
      peroxisomes contain at least two enzymes necessary for the initial steps in
      cholesterol synthesis, i.e., thiolase and mevalonate kinase. The rate-limiting
      enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase,
      is also localized in peroxisomes and exhibits a cyclic variation distinct from
      that of the reductase found in the endoplasmic reticulum. The largest
      concentration of cellular sterol carrier protein-2 is localized in peroxisomes as
      well as a number of enzymes required for the conversion of lanosterol to
      cholesterol. Furthermore, peroxisomes are involved in the in vitro synthesis of
      cholesterol and dolichol from mevalonate and have been shown to contain
      significant levels of apolipoprotein E, a major constituent of several classes of
      plasma lipoproteins. Moreover, cholesterol synthetic capacity is impaired in
      cultured skin fibroblasts obtained from patients with peroxisomal deficiency
      diseases.

PMID- 1356378
TI  - Medtronic Cardiovascular Technology Symposium. Proceedings. Turnberry, Scotland,
      October 24-27, 1991.

PMID- 1356379
TI  - Allele frequencies of cystic fibrosis-linked markers and F508 deletion in
      affected Hungarian families.
AB  - Linked marker haplotype analysis of 16 cystic fibrosis (CF)-affected children, 3
      fetuses, 1 healthy child and their parents was performed by restriction fragment
      length polymorphism (RFLP) for J3.11, Met H, Met D, XV-2c, KM.19 markers.
      Polymerase chain reaction (PCR) to detect the main mutation of CF chromosome, a
      specific 3 base pair (bp) deletion (delta F508) was also performed in 17 CF
      patients. Allelic frequencies on analysed CF chromosomes were: J3.11/Taq I 1.0,
      0.0, J3.11/Msp I 0.44, 0.56, Met H/Taq I 0.73, 0.27, Met H/Msp I 0.80, 0.20, Met
      D/Taq I 0.75, 0.25, XV-2c/Taq I 0.85, 0.15, KM.19/Pst I 0.17, 0.83 for allele 1
      and 2, respectively. Two markers, Met H and KM.19 were found to be in strong
      association with the CF mutation. The frequency of the delta F508 mutation on all
      34 CF chromosomes was 0.65 (of which 0.73 was homozygous and 0.27 heterozygous
      for this deletion).

PMID- 1356377
TI  - Chinese hamster ovarian cell glycoproteins that mediate type 1 piliated gram
      negative bacterial adherence.
AB  - We used Chinese hamster ovary (CHO) cell lines to define the structures of
      glycoproteins responsible for Type 1 piliated bacterial adherence. CSH 50
      Escherichia coli, a Type 1 piliated bacteria, adhered significantly better than
      an isogenic nonpiliated E. coli to all CHO lines tested. CSH 50 E. coli adhered
      least well to CHO cells expressing intact complex type oligosaccharides on cell
      surface glycoproteins. CSH 50 adherence increased when shorter oligosaccharides
      were present and was maximal when mannose groups were present in terminal,
      nonreducing positions. Five high mannose type glycoproteins, with molecular
      weights of 79, 75, 55, 50, and 37 kD, were identified as high affinity ligands
      for Type 1 piliated bacteria. Our results suggest that alterations in cell
      surface carbohydrates may increase adherence of Type 1 piliated gram-negative
      bacteria to cells.

PMID- 1356380
TI  - About DR beta-restriction fragment length polymorphism (RFLP) analysis in kidney
      transplantation in connection with a paediatric patient.
AB  - A retrospective analysis of the HLA-DR antigens was performed at the DR beta DNA
      locus by the means of restriction fragment length polymorphism (RFLP) in the case
      of a two-times kidney transplanted paediatric patient and in 16 adult kidney
      donor recipient pairs in order to prove the importance of DNA molecular analysis
      in those cases where the serological identification is poor. The child and her
      grafts (first from her mother, the second from a cadaver donor) carried the DRw6
      antigen which serologically can very poorly be defined. According to DR
      serotyping before transplantation both the child and the cadaver kidney proved to
      be DR5, 6, while the DNA analysis revealed mismatches; the child possessed the
      two subtypes: 13b1 and 14a of the DRw6 antigen only and none of the DR5, the
      cadaver kidney proved to belong to the DR4 antigen group instead of DR5, and
      furthermore to a different subtype of the DRw6 (13a3) than the recipient. The DNA
      analysis of other 16 adult donor-recipient pairs also underlined the importance
      of the DR beta RFLP analysis in cases where the transplantation antigens could be
      poorly defined.

PMID- 1356383
TI  - Proceedings of the 1991 International Congress of Rhinology. Tokyo, Japan.

PMID- 1356382
TI  - Isolation of high-molecular-weight DNA from small samples of blood having
      nucleated erythrocytes, collected, transported, and stored at room temperature.
AB  - Blood samples collected in the field for isolating DNA suitable for molecular
      analysis need special care in their storage and handling. In this article, we
      describe a simple method for the isolation of good-quality high-molecular-weight
      DNA that does not require low temperature conditions during collection, storage,
      and/or transportation of blood samples. This method involves smearing small
      aliquots of blood onto clean slides and air drying them at room temperature. The
      slides with blood smears can then be transported or stored at room temperature
      and still serve as a very good source of high-molecular-weight DNA. Genomic DNA
      from these samples can be extracted by organic phase separation (phenol
      chloroform extraction) after lysis. The DNA thus obtained is of high quality and
      yields DNA fingerprints qualitatively similar to those prepared from
      corresponding control DNA isolated from frozen blood samples. Needing minimal
      facilities at field sites, the method is very convenient for conducting RFLP
      analysis of wild/field populations for demographic, behavioral, and ecologic
      studies.

PMID- 1356381
TI  - CpG islands in mammalian gene promoters are inherently resistant to de novo
      methylation.
AB  - The CpG islands found at the 5' ends of many mammalian genes are typically
      unmethylated despite being both exposed to diffusible protein factors in nuclei
      and rich in CpG, the target site for DNA methyltransferase. We show here that the
      CpG islands associated with the human Thy-1 and profilin genes are inherently
      resistant to de novo methylation by purified murine DNA methyltransferase, and
      that the higher than expected tendency of CpG sites in islands to be flanked on
      both sides by G-C base pairs is the likely reason for the resistance. Several
      lines of evidence indicate that DNA methyltransferase does not make base-specific
      contacts with residues that flank CpG sites, and it is likely that CpG sites
      within islands are resistant to de novo methylation because of local
      conformational features such as ease of strand separation, minor groove
      dimensions, and alternative secondary structures. A role for minor groove
      contacts is consistent with the presence within a putative regulatory domain of
      numerous modified beta turn structural elements that can make minor groove
      contacts.

PMID- 1356384
TI  - Fireside conference 1. Autonomic nerve control of the nasal mucosa.

PMID- 1356385
TI  - An investigation of the molecular basis of nontypable Haemophilus influenzae
      adherence to mucosal epithelium.

PMID- 1356386
TI  - Takayasu's arteritis associated with Wiskott-Aldrich syndrome.
AB  - A unique case of a Chinese boy with Wiskott-Aldrich syndrome (WAS) associated
      with Takayasu's arteritis is reported. He had eczema, epistaxis and recurrent
      infections since early infancy and was found to have thrombocytopenia, negative
      delayed-type skin hypersensitivity, low T cell number and impaired lymphocyte
      proliferation to phytohaemagglutinin and concanavalin A. He had high normal serum
      immunoglobulin (Ig)G and IgA with low IgM and isohaemagglutinin. He presented
      with hypertensive encephalopathy at 5.5 years of age and an aortogram
      demonstrated abdominal aortic aneurysm with bilateral stenosis of renal arteries
      resulting in renovascular hypertension. His hypertension was difficult to control
      medically and autotransplant of his kidneys to the iliac arteries was performed,
      but he died in the immediate postoperative period. The relationship between
      immunodeficiency and collagen-vascular disease was discussed.

PMID- 1356388
TI  - Allelic loss on chromosome 11p is a less frequent event in bilateral than in
      unilateral Wilms' tumours.
AB  - Analyses to detect loss of heterozygosity (LOH) were performed at 11 polymorphic
      loci on chromosome 11 and, using a polymorphic CA repeat sequence in the WT1
      gene, on a series of 39 tumours from 28 unilateral and 10 tumours from 6
      bilateral Wilms' tumour (WT) patients. LOH was seen in 13 out of 35 patients
      including 12 out of 29 unilateral tumours, but only one of 10 bilateral tumours.
      This suggests that bilateral WT represents a subgroup of WT in which tumour
      initiating events less frequently involve LOH on chromosome 11 and that either
      epigenetic events, point mutations or another non-chromosome 11p locus are
      important in bilateral tumours. The observation of LOH in one WT but not another
      WT in a bilateral WT patient provides evidence that these tumours arising in the
      same patient are not monoclonal proliferations and most likely arise via
      different molecular pathways.

PMID- 1356387
TI  - c-myc gene amplification in selected node-negative breast cancer patients
      correlates with high rate of early relapse.
AB  - In breast cancers with histologically negative axillary nodes selected for high
      frequency of recurrence, the amplification of c-myc, erbB-2 and int-2 genes was
      found to concern, respectively 25% (16/65), 31% (25/81) and 14% (10/70) of
      tumours. Their relation with tumour progression expressed by relapse-free
      survival is reported. Using univariate analyses, c-myc amplified tumours showed
      significant association with early (30-month period after diagnosis) (P = 0.0013)
      and intermediate (50-month period after diagnosis) (P = 0.0398) risks of
      recurrence. In contrast, only a trend towards higher relapse was observed in erbB
      2 amplified breast cancers with respect to later events (occurring over the first
      30-month period). Multivariate analyses indicated that c-myc amplification is an
      independent prognostic factor stronger than oestrogen receptor status and tumour
      size to define a high risk subset in node-negative patients selected for high
      frequency of recurrence.

PMID- 1356390
TI  - A European view of fluoride supplementation.
AB  - During the autumn of 1991 a meeting was convened in Brussels by Colgate entitled
      'European view of fluoride supplementation'. Throughout Europe, product dosage
      and age related dose recommendations for fluoride supplements vary widely. With
      the advent of 1992, different instructions on the same packet would cause
      considerable confusion in a more integrated Europe with its mobile and
      multilingual society. Colgate therefore decided to convene a meeting of European
      experts to explore the possibility of reaching a consensus on a common dosage
      regime of fluoride tablets and drops for Europe. The meeting consisted of a
      series of short papers by European experts in the field followed by detailed
      discussion.

PMID- 1356389
TI  - Spindle cell ploidy and proliferation in endemic and epidemic African Kaposi's
      sarcoma.
AB  - Comparative studies of ploidy and proliferative activity of spindle cells in
      sections of 20 (skin, 17; lymph node, 3) biopsy specimens from African patients,
      10 with endemic Kaposi's sarcoma (EKS) and 10 with AIDS-associated Kaposi's
      sarcoma (AKS) were performed by histopathology, feulgen-based DNA measurement and
      proliferating cell nuclear antigen (PCNA)/cyclin immunohistochemistry,
      respectively. All specimens were classified as nodular lesions with basically the
      same histology. In 17 cases immunostained for cyclin/PCNA, the percentage of
      proliferating spindle cells range between 2-18, with a higher mean rate in AKS
      although this was not statistically significant. In situ measurement of DNA
      showed no significant values greater than the diploid level of control cells
      indicating that spindle cells in both EKS and AKS have euploid DNA content. Our
      findings indicate that both EKS and AKS represent the same type of euploid low
      rate cell proliferations. This corroborates previous suggestions that KS could
      represent a reactive process to yet undefined stimulus rather than a clonal
      proliferation, of transformed malignant cells.

PMID- 1356391
TI  - Diseases of the salivary glands.

PMID- 1356393
TI  - Immunologic effector cells in head and neck cancer.
AB  - Freshly isolated tumor-infiltrating lymphocytes (TIL) and lymph node lymphocytes
      (LNL) in patients with head and neck cancer (HNC) often have low or undetectable
      functional responses. Because impaired ability of these cells to produce
      cytokines could be responsible for their functional incompetence, spontaneous and
      in vitro-induced production of interleukin-2 (IL2), interleukin-1 beta (IL-1
      beta), tumor necrosis factor-alpha (TNF-alpha), and interferon gamma (IFN-gamma)
      by TIL, LNL from tumor-free as well as tumor-involved lymph nodes (LN), and
      peripheral blood lymphocytes (PBL) were measured. Although TIL or PBL of patients
      with HNC produced IL-1 beta and TNF-alpha spontaneously or after in vitro
      activation, LNL did not produce measurable levels of these cytokines. LNL also
      produced lower levels of IFN-gamma than PBL. In situ hybridization for cytokine
      mRNA performed with tumor tissues, and LN of patients with HNC showed that TIL as
      well as LNL localized in the immediate proximity of the tumor were activated, as
      evidenced by the expression of mRNA for IL2, IFN-gamma, IL-1 beta, TNF-alpha, and
      both alpha- and beta-chains of the IL2 receptor. In addition, many LNL located
      next to the tumor expressed mRNA for transforming growth factor-beta (TGF-beta).
      In contrast, LNL not adjacent to the tumor in involved LN, as well as those in
      tumor-uninvolved LN, did not express mRNA for cytokines or IL2 receptor.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1356392
TI  - Biology of and novel therapeutic approaches for epithelial cancers of the
      aerodigestive tract. Proceedings of a conference. Steamboat Springs, Colorado,
      April 1-7, 1991.

PMID- 1356394
TI  - Keratinocyte differentiation markers: involucrin, transglutaminase, and toxicity.
AB  - Studies of three keratinocyte differentiation markers are described. First, the
      involucrins of several mammals are identified, facilitating use of this marker in
      animal models of human disease. The rapid evolution of involucrin has prevented
      its routine immunochemical identification beyond the primates, but its unusual
      solubility and its labeling by transglutaminase have permitted detection in rats,
      cats, and sheep. Second, the re-expression of keratinocyte transglutaminase in
      carcinoma cells lacking the enzyme is demonstrated. Lack of this enzyme
      expression has been observed previously in squamous cell carcinomas. The present
      finding suggests genomic hypermethylation could contribute to this phenomenon and
      offers an approach to analyzing transcriptional features of the enzyme
      regulation. Third, the sensitivity of keratinocytes to growth suppression by
      aflatoxin B1 is reported. The observed toxicity appears to be mediated by aryl
      hydrocarbon hydroxylase, a metabolic enzyme inducible in keratinocytes by
      environmental agents. Such expression may be relevant to carcinogenesis in
      tissues subject to squamous metaplasia as well as in other exposed cell types
      stimulated to express this biotransformation enzyme.

PMID- 1356395
TI  - Antihypertensive drugs and plasma lipids.

PMID- 1356396
TI  - Fade during recovery from vecuronium.

PMID- 1356397
TI  - Onset of neuromuscular block in myasthenic patients.

PMID- 1356398
TI  - Dose-response relationships for neostigmine antagonism of vecuronium-induced
      neuromuscular block in adults and the elderly.
AB  - We have studied the dose-response relationship for neostigmine in 36 adult (ages
      18-50 yr) and 36 elderly (ages > 70 yr) subjects during antagonism of
      neuromuscular block induced by vecuronium. All patients received vecuronium 0.08
      mg kg-1 and neuromuscular block was monitored mechanomyo-graphically using the
      train-of-four (TOF) mode of stimulation. Six patients of each age group were
      allocated randomly to receive neostigmine 5, 15, 25, 35 or 45 micrograms kg-1 or
      saline at 10% recovery of T1 (first response in the TOF). TOF ratios were
      recorded continuously over the next 10 min and the values at 1-min intervals from
      5 min onwards were used to construct the dose-response relationships. There was a
      significant difference (P < 0.05) in the time to spontaneous recovery of T1 to
      10% between the adults (24 (SD 5.5) min) and the elderly (33 (7.8) min). Dose
      response curves for neostigmine were parallel in the two age groups, but those
      for the elderly were significantly to the right of the curves for the adults.
      This suggests an apparently lesser relative potency of neostigmine, or the
      requirement of a larger dose, in the elderly for attaining antagonism of a
      moderately intense vecuronium block at the same time as in adults.

PMID- 1356399
TI  - Relative pre- and postjunctional effects of a new vecuronium analogue, Org 9426,
      at the rat neuromuscular junction.
AB  - We have studied the relative pre- and postjunctional neuromuscular blocking
      effects of Org 9426 in the isolated rat hemidiaphragm muscle using twitch tension
      and electrophysiological recording techniques. Postjunctional effects were
      assessed from decreases in twitch height and from end-plate current amplitude and
      time constant of decay. Prejunctional effects were assessed from the fade of
      tetanic twitch tension and end-plate current amplitude rundown. There were no
      significant differences between the relative pre- and postjunctional effects of
      Org 9426 and those of previously studied steroidal neuromuscular blocking
      compounds. It is concluded, therefore, that the rapid onset and short duration of
      Org 9426 seen in vivo is not a consequence of a strong prejunctional, relative to
      postjunctional, blocking effect of the compound.

PMID- 1356400
TI  - Lung function after vecuronium pretreatment in young, healthy patients.
AB  - Lung function and clinical evidence of muscle weakness were assessed in 12 ASA I
      patients who received vecuronium 0.01 mg kg-1 pretreatment as a part of their
      anaesthetic management, before and 3 min after pretreatment. Most patients
      demonstrated ptosis and diplopia, while five of the 12 were unable to raise the
      head for > 4 s and had difficulty in swallowing. Significant reductions occurred
      in forced vital capacity, forced expiratory volume in 1 s, and maximum mid
      expiratory flow rate. Among static lung volumes, functional residual capacity and
      expiratory reserve volume decreased significantly. However, these changes were
      not serious enough to cause clinically significant impairment of coughing or a
      decrease in oxygen saturation in any patient.

PMID- 1356402
TI  - Mitotic inhibitors.

PMID- 1356401
TI  - Endocrine tumors.

PMID- 1356403
TI  - Multidrug resistance.

PMID- 1356404
TI  - Inhibitory effects of glyceryl trinitrate on alpha-adrenoceptor mediated
      contraction in the human internal mammary artery.
AB  - 1. Sympathomimetic amines have been considered to be related to vasospasm.
      Previous studies showed that the human internal mammary artery (IMA) was capable
      of weak beta-adrenoceptor mediated relaxation and that alpha-adrenoceptor
      agonists may induce contraction in the human IMA. 2. We investigated the effects
      of glyceryl trinitrate (GTN), a vasodilator agent often used perioperatively, on
      alpha-adrenoceptor mediated contraction in the human IMA. 3. Discarded human IMA
      segments were taken from 37 patients who underwent IMA--coronary artery bypass
      graft operations and equilibrated in an organ bath. 4. A specially designed
      technique was used to normalize the vessel segments under the pressure similar to
      the in vivo situation. Noradrenaline (NA), phenylephrine (PE), and methoxamine
      (MO) were used to contract the vessel segments. 5. GTN fully relaxed PE or MO
      (submaximal concentration) induced precontraction. Therapeutic plasma
      concentration of GTN relaxed 40-90% of the PE induced contraction (2.82 g, EC50 =
      7.92 +/- 0.06 -log M) and 20-90% of the MO induced contraction (1.8 g, EC50 =
      7.63 +/- 0.16 -log M). Pretreatment by the therapeutic plasma concentration of
      GTN inhibited the contraction induced by NA, PE in a different range. It reduced
      the NA induced contraction (6.9 g) by 14.8-38% (P greater than 0.05) and the PE
      induced contraction (4.3 g) by 7.9-39.3% (P greater than 0.05). The alpha 1
      adrenoceptor antagonist prazosin, at the therapeutic plasma concentration, nearly
      totally abolished the NA or PE induced contraction (P less than 0.001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1356405
TI  - Beta-adrenoceptor antagonists enhance white blood cell aggregation in patients
      with ischaemic heart disease.
AB  - The effects of beta-adrenoceptor antagonists, calcium channel blockers and long
      acting nitrates on white blood cell (WBC) aggregation were studied in patients
      with ischaemic heart disease. WBC aggregation was significantly increased by beta
      adrenoceptor antagonists (P = 0.011) but was unaffected by either calcium channel
      blockers or long acting nitrates. Enhanced WBC aggregation promotes microvascular
      occlusion and damage.

PMID- 1356406
TI  - Direct enantiomeric separation of beta-blockers on ChyRoSine-A by supercritical
      fluid chromatography: supercritical carbon dioxide as transient in situ
      derivatizing agent.
AB  - The direct enantiomeric separation of a series of beta-blockers has been carried
      out on two chiral stationary phases (CSPs) derived from 3,5-dinitrobenzoyl
      tyrosine: the commercially available ChyRoSine-A and a recent improved version of
      this CSP. Using supercritical fluid chromatography (SFC), facile separations are
      achieved (1.1 less than Rs less than 7) within short analysis times. The
      parameters affecting the enantioselectivity (temperature, pressure, mobile phase
      nature, solute structure) have been investigated. The optimal mobile phase
      consists in a mixture of carbon dioxide-methanol-propylamine at 25 degrees C. The
      solute structure has a great influence on the enantioselectivity. For instance,
      both amine and hydroxyl protons are necessary for chiral discrimination to occur.
      Furthermore, the steroselectivity value is directly connected to the amine
      substituent steric bulkiness. Surprisingly, these solutes are poorly resolved
      using normal phase liquid chromatography (NPLC). Accordingly, the specific
      influence of carbon dioxide on the enantiomeric separation of 1,2-amino-alcohols
      have been investigated using various techniques such as nuclear magnetic
      resonance (NMR) or molecular modelisation. It has been shown that carbon dioxide
      acts as a complexing agent toward the amino-alcohol by setting up of a bridge
      with the hydroxyl and the amine protons of the solute. In that way, the resulting
      complex possesses lower acido-basic properties and a higher conformational
      rigidity, responsible for chiral discrimination.

PMID- 1356408
TI  - Global programme on AIDS. Unexplained severe immunosuppression without evidence
      of HIV infection.

PMID- 1356407
TI  - The alpha 1, alpha 2, and alpha 3 subunits of GABAA receptors: comparison in
      seizure-prone and -resistant mice and during development.
AB  - Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in brain,
      opens chloride channels through actions on GABAA receptors. We now report base
      and amino acid sequences of the alpha 1, alpha 2, and alpha 3 subunits from GABAA
      receptors of audiogenic seizure-prone (DBA/2J) and -resistant (C57BL/6J) inbred
      strains of mice. Inbreeding had fixed different alleles of the alpha 1 subunit in
      the two strains, giving five base differences in the cDNAs. None of these
      affected amino acid sequence, but one did create a NsiI restriction site
      potentially useful in mapping genomic DNA. No base or amino acid sequence
      differences between the strains were detected for the other two subunits.
      Northern blots revealed no apparent strain differences in message levels for
      these three subunits in whole brains of the mice at 3 weeks of age, the peak of
      seizure susceptibility in DBA/2J, but did reveal distinct regional and
      developmental patterns of expression among the subunits in mouse brain.

PMID- 1356410
TI  - Differential effect of griseofulvin on interferon-gamma-induced HLA-DR and
      intercellular adhesion molecule-1 expression of human keratinocytes.
AB  - Interferon-gamma (IFN-gamma) induces major histocompatibility complex (MHC) class
      II antigen and intercellular adhesion molecule-1 (ICAM-1) expression on human
      epidermal keratinocytes. Griseofulvin, an extensively used antifungal agent, has
      been used effectively in the treatment of lichen planus, in which keratinocytes
      express both HLA-DR and ICAM-1 antigens. In this study, we investigated the
      effect of griseofulvin on IFN-gamma-induced MHC class II antigen and ICAM-1
      expression of keratinocytes, and demonstrated that griseofulvin decreased IFN
      gamma-induced HLA-DR but not ICAM-1 expression.

PMID- 1356409
TI  - Preferential adherence of T lymphocytes and neutrophils to psoriatic epidermis.
AB  - T lymphocytes and neutrophils accumulate in psoriatic epidermis. To determine
      whether the epidermis plays an active role in this process through the production
      of cellular adhesion factors, leucocyte adherence to lesional psoriasis was
      compared with normal skin in a modified frozen-section adhesion assay. Lymphocyte
      and neutrophil suspensions were prepared by standard Ficoll-Hypaque techniques
      from peripheral blood of normal volunteers and overlaid on to glutaraldehyde
      fixed 8-microns cryostat sections of skin. Adhesion of phorbol ester-activated T
      lymphocytes to the epidermis was significantly greater in psoriasis compared with
      normal skin (P < 0.01). Adhesion was absent (a) at 7 degrees C, (b) in the
      presence of EDTA and (c) in the absence of lymphocyte activation. Immunostaining
      demonstrated that all adherent lymphocytes were CD3+ve (i.e. T cells). Likewise,
      neutrophils adhered more prominently to psoriatic epidermis. Adhesion was most
      prominent at the tips of dermal papillae, corresponding to areas of maximal
      intercellular adhesion molecule-1 (ICAM-1) expression. Both neutrophils and
      lymphocytes adhered to dermal papillary vascular endothelium. These studies
      provide functional data that psoriatic epidermal cells are actively involved in
      leucocyte adherence. The distribution of adhesion suggests that both ICAM-1
      dependent and independent mechanisms are involved.

PMID- 1356411
TI  - The pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea
      pig.
AB  - The pre-ulcerative phase of carrageenan-induced colonic ulceration was
      investigated in guinea-pigs supplied 3% degraded carrageenan as an aqueous
      solution as drinking fluid for 2 or 3 days during which no ulceration of the
      bowel was observed with the naked eye or dissecting microscope. Mucosal
      microscopic changes, from caecum to rectum, were multifocal and included cellular
      infiltrates, dilatation of glands, crypt abscesses, micro-ulcers and sulphated
      polysaccharide in the lamina propria. Sulphated polysaccharide was also
      demonstrated histologically for the first time within the surface epithelium and
      showed ultrastructural features similar to carrageenan. The results indicate that
      colonic epithelium in the guinea-pig is capable of macromolecular absorption.
      Carrageenan, a highly active polyanionic electrolyte, within the surface
      epithelial cells is most likely a primary factor in the breakdown of mucosal
      integrity. Macromolecular absorption causing enteropathy of the large bowel is a
      new pathophysiological concept which may have implications in man, particularly
      in the pathology of large bowel disease.

PMID- 1356412
TI  - GAA(Glu)272----AAA(Lys) and CGA(Arg)1941----CAA(Gln) in the factor VIII gene in
      two haemophilia A patients of Czech origin.

PMID- 1356413
TI  - The spectrum of beta thalassaemia in Burma.
AB  - The molecular defects causing beta thalassaemia have been analysed in 85
      unrelated Burmese patients. The patients included 14 with homozygous beta
      thalassaemia, 70 with HbE/beta thalassaemia and one with HbS/beta thalassaemia.
      Using a combination of allele-specific oligoprobe hybridization and direct
      sequencing of genomic DNA amplified by the polymerase chain reaction, 95/99 of
      the beta-thalassaemia alleles have been characterized. Six mutations have been
      identified of which three, the G-T at IVS-1 position 1, the G-C at IVS-1 position
      5 and the deletion of TCTT in codons 41/42, accounted for 85% of the alleles.
      Despite the diversity of ethnic groups in Burma, the number of beta-thalassaemia
      alleles in Burma is relatively small. Thus, diagnosis of the majority of the beta
      thalassaemias would be possible using a limited number of oligonucleotide probes.

PMID- 1356414
TI  - The role of the spleen after bone marrow transplantation for primary
      myelofibrosis.

PMID- 1356416
TI  - Advances in cancer chemotherapy. Proceedings of a symposium held in conjunction
      with the 6th European Conference on Clinical Oncology. Florence, Italy, October
      29, 1991.

PMID- 1356415
TI  - An adapter for defined sample volumes makes it possible to count absolute
      particle numbers in flow cytometry.
AB  - A device is described which makes it possible to count absolute particle (cell)
      numbers per volume by flow cytometry. It can easily by adapted to several types
      of flow cytometers, especially to the Coulter EPICS V and EPICS 750 series. A
      volume adapter has been installed in place of the normal sample handling system
      without any further modifications of the instrument or the data acquisition
      program. The adapter consists of a special pipette with two opto-electronic
      detectors for the beginning and end of the measuring period. These switch on/off
      a shutter for the illuminating laser beam so that acquisition of the data is
      controlled indirectly. Sample volumes of 50 microliters were measured at flow
      rates up to 10(3) particles/s. Calibration beads as well as blood cells were
      enumerated according to FALS (forward angle light scatter), to SSC (90 degrees
      light scatter), and to fluorescence parameters. The results were compared to the
      evaluation made on a Coulter counter or in a Neubauer chamber of a light
      microscope. Using a concentration of 1 x 10(5)-5 x 10(5) particles/ml, the
      absolute numbers of particles were determined with a high reproducibility and an
      estimated error rate of 2-5%.

PMID- 1356417
TI  - Reversible G1 arrest induced by dimethyl sulfoxide in human lymphoid cell lines:
      kinetics of the arrest and expression of the cell cycle marker proliferating cell
      nuclear antigen in Raji cells.
AB  - In order to elucidate further the mechanism of reversible cell cycle arrest
      induced by treatment of Raji cells with 1.5% dimethyl sulfoxide (DMSO), we have
      performed a detailed analysis of the kinetics of arrest and of reentry into the
      cell cycle after removal of DMSO and have correlated cell cycle progression with
      expression of proliferating cell nuclear antigen (PCNA). No significant effect of
      DMSO on cell cycle patterns, assessed by flow cytometric analysis of
      bromodeoxyuridine-prelabeled cells, was seen for the first 19 h of treatment. A
      clear reduction of entry into S phase was detected by about 25 h of treatment;
      essentially all cells were arrested with a G1 content of DNA after 96 h of
      treatment. When DMSO-arrested cells were released from the block, entry into S
      phase began at 12 h after release and continued in a fairly asynchronous manner
      for a further 12-14 h. In arrested cells, the content of PCNA was reduced to
      about 25% of the amount present in logarithmically growing G1 phase cells. Six h
      after release from DMSO, PCNA RNA transcripts were first detected by Northern
      blotting. The increase of PCNA protein, detected by Western blotting, was seen by
      9 h after release. The kinetics of entry into the cell cycle and restoration of
      PCNA protein are similar to that seen in serum stimulation of quiescent cells.
      These results suggest that DMSO reversibly arrests proliferation of Raji cells at
      G0 or at an early point in G1 phase and that progression through late G1 phase
      and entry into S phase are correlated with synthesis of the PCNA gene product.

PMID- 1356418
TI  - Activation of multidrug resistance (P-glycoprotein) mdr3/mdr1a gene during the
      development of hepatocellular carcinoma in hepatitis B virus transgenic mice.
AB  - The expression of multidrug resistance (mdr) genes was investigated in the livers
      of transgenic mice that express the human hepatitis B virus large envelope
      polypeptide under the transcriptional control of a liver-specific promoter. These
      mice develop a storage disease due to the accumulation of a nonsecretable form of
      hepatitis B surface antigen in the hepatocyte. Liver cell injury is followed by a
      hepatocellular proliferative response, dysplasia, microscopic nodular
      hyperplasia, and finally hepatocellular carcinoma. The expression of mdr1, mdr2,
      and mdr3 genes was analyzed in livers at different stages of the disease by RNase
      protection assay, Western blot, and immunohistochemistry. RNase protection assay
      revealed that mdr3 mRNA expression was moderately increased in tissue with
      microscopic nodular hyperplasia and significantly overexpressed in hepatocellular
      carcinoma but undetectable in earlier stages of the disease. Western blot using
      isoform-specific anti-mdr3 antibody demonstrated that the expression of mdr3
      protein reflected the steady-state level of mdr3 mRNA. Immunohistochemical
      analyses using anti-mdr3 isoform-specific antibody and monoclonal antibody C219,
      which recognizes all the three mdr isoforms, demonstrated selective
      overexpression in preneoplastic foci during the stage of microscopic nodular
      hyperplasia as well as in neoplastic hepatocytes in hepatocellular carcinoma. No
      consistent activation of mdr1 and mdr2 (but occasional coactivation with mdr1)
      genes during hepatocarcinogenesis was observed. Our results suggest that the
      hepatocellular mdr3-specific activation mechanism is associated with the late
      events of hepatocarcinogenesis in this model. The predictable kinetics of mdr
      gene expression in this transgenic tumor model suggest that it is suitable for
      future studies of the mechanism of mdr gene activation and the possible
      pharmacological consequences for mdr3 gene expression of hepatocellular
      carcinoma.

PMID- 1356419
TI  - The management of persistent or recurrent variceal bleeding after injection
      sclerotherapy by somatostatin.
AB  - Sixteen patients with persistent (n = 11) or recurrent (n = 5) variceal bleeding
      after injection sclerotherapy and balloon tamponade were treated with an
      intravenous infusion of somatostatin 250 micrograms/h. Somatostatin infusion
      successfully controlled the bleeding in 15 of the 16 patients but one rebled
      after 72 h of treatment. In one patient with poor liver function (Child's C)
      bleeding was not controlled by somatostatin, further injection sclerotherapy or
      balloon tamponade of the oesophagus. The results of this study, although
      uncontrolled and with a small number of patients, suggest that somatostatin is a
      very effective treatment for the control of post-injection sclerotherapy variceal
      bleeding.

PMID- 1356420
TI  - Partial pancreaticoduodenectomy (Whipple procedure) for pancreatic malignancy:
      occlusion of a non-anastomosed pancreatic stump with fibrin sealant.
AB  - Following partial pancreaticoduodenectomy for periampullary and pancreatic
      cancer, the complication and mortality rates are particularly high. Various
      approaches have aimed at improving the postoperative result, with less than
      complete success. The discouraging results of others, and our own
      dissatisfaction, led us to evaluate an atraumatic, sutureless method for
      management of the residual gland. Following head resection, the remaining
      pancreas is occluded with a fibrin sealant (Tisseel c, Immuno AG, Vienna) via
      injection into the pancreatic duct, which is then ligated and left free in the
      peritoneal cavity. Among 44 patients treated with this method, there were no
      perioperative deaths. Three patients developed local complications (2 fistulae, 1
      pancreatitis) due to technical errors that presumably resulted in incomplete
      occlusion. Evaluation of patients after two to three years indicates that the
      endocrine function of the pancreas has been largely conserved despite ductal
      occlusion.

PMID- 1356422
TI  - World Association of HPB Surgery, 4th World Congress. Hong Kong, 7-11 June 1992.
      Abstracts.

PMID- 1356421
TI  - Somatostatin for bleeding oesophagitis or ulceration after sclerotherapy for
      oesophageal varices.

PMID- 1356423
TI  - Neurotransmitter-specific identification and characterization of neurons in the
      all-cone retina of Anolis carolinensis. II: Glutamate and aspartate.
AB  - Immunocytochemical and autoradiographic methods were used to identify neurons in
      the pure cone retina of the lizard (Anolis carolinensis) that are likely to
      employ glutamate (GLU) or aspartate (ASP) as a neurotransmitter. GLU
      immunocytochemistry demonstrated high levels of endogenous GLU in all cone types
      and numerous bipolar cells. Moderate GLU levels were found in horizontal and
      ganglion cells. Muller cells and most amacrine cells had very low GLU levels. GLU
      immunoreactivity (GLU-IR) in the cones was present from the inner segment to the
      synaptic pedicle. A large spherical cell type with moderate GLU-IR was identified
      in the proximal inner plexiform layer (IPL). These cells also contain ASP and
      have been tentatively identified as amacrine cells. Uptake of [3H]-L-GLU labeled
      all retinal layers. All cone types and Muller cells sequestered [3H]-D-ASP, a
      substrate specific for the GLU transporter. Anti-ASP labeling was observed in
      cones, horizontal cells, amacrine cells, and cells in the ganglion cell layer.
      ASP immunoreactivity (ASP-IR) in the cones was confined to the inner segment. One
      ASP-containing pyriform amacrine cell subtype ramifying in IPL sublamina b was
      identified. Analysis of GLU-IR, ASP-IR, and GABA-IR on serial sections indicated
      that there were two distinct populations of horizontal cells in the Anolis
      retina: one containing GABA-IR, GLU-IR, and ASP-IR; and another type containing
      only GLU-IR and ASP-IR. Light GLU-IR was frequently found in GABA-containing
      amacrine cells but ASP-IR was not. The distinct distributions of GLU and ASP may
      indicate distinctly different roles for these amino acids. GLU, not ASP, is
      probably the major neurotransmitter in the cone-bipolar-ganglion cell pathway of
      the Anolis retina. Both GLU and ASP are present in horizontal cells and specific
      subpopulations of amacrine cells, but it is unclear if GLU or ASP have a
      neurotransmitter role in these cells.

PMID- 1356424
TI  - The effect of illness duration on perceptual asymmetry in schizophrenia.
AB  - Perceptual asymmetry in a group of schizophrenic subjects who were clinically
      stable and living in the community was compared with a group of normal control
      subjects matched for age and sex using a dichotic monitoring task of language
      processing. Schizophrenic subjects showed reduced target detection and slower
      reaction times for both left and right ear inputs. In relation to performance
      asymmetry, the schizophrenic subjects had a reduced speed of responding to left
      ear items compared to normal controls. Within the schizophrenic group differences
      in performance emerged according to duration of illness. Shorter duration of
      illness was associated with poorer target detection overall and comparatively
      greater magnitude of the normal right ear advantage. The latter was accounted for
      by a relative augmentation of the normal left ear performance decrement. These
      results were partly reflected in the reaction time measures. The findings suggest
      that as illness duration increases there may be a tendency for certain aspects of
      the information processing abnormality in schizophrenia to normalise, in spite of
      continued deficits as reflected in prolonged reaction times.

PMID- 1356425
TI  - Deficits in initial feature registration of schizophrenics and substance abusers.
AB  - Information processing deficits are consistently reported for schizophrenics. The
      present study evaluated if the longer duration required by schizophrenics to
      visually recognize a target may qualify, as proposed by previous studies, as a
      vulnerability and/or trait biological marker. Critical stimulus duration (CSD)
      was used as the index of initial target registration and recognition. The CSD is
      the minimal duration, in ms, to meet task criterion, which in the present study
      was seven consecutive identifications of the target letter 'T' or 'A'. There were
      13 normal controls, 11 methadone maintenance experimental controls, 21 chronic
      schizophrenics and 12 subacute schizophrenics. Analysis of variance revealed that
      the CSDs of normal controls and subacute schizophrenics were not statistically
      different (p > 0.05); the CSDs of chronic schizophrenics were not statistically
      different from methadone controls (p > 0.05), while the chronic schizophrenics
      and the methadone controls' CSDs were statistically different from the normal
      controls and the subacute schizophrenics. The results support earlier reports of
      long target duration required by chronic schizophrenics for feature recognition.
      Since retarded CSDs were obtained for methadone control but not for acute
      schizophrenics, the CSD does not qualify as a specificity or a vulnerability
      index for schizophrenia. A neurophysiological explanation is proposed for the
      findings.

PMID- 1356426
TI  - Platelet monoamine oxidase in schizophrenia: a meta-analysis.
AB  - We did a meta-analysis on all publications (English and other languages)
      concerned with platelet monoamine oxidase (MAO) in schizophrenia. Essentially,
      when patients were medicated with a neuroleptic, most studies found that
      schizophrenics had lower platelet MAO levels than controls. Administration of
      neuroleptic lowers MAO levels. MAO levels in drug-free schizophrenics were
      similar to controls. Only a minority of studies found drug-free schizophrenics
      had decreased platelet MAO levels.

PMID- 1356427
TI  - Occurrence of antigen-specific B cells following oral or parenteral immunization
      with Porphyromonas gingivalis fimbriae.
AB  - The induction and distribution of antigen-specific antibody-secreting cells in
      various tissues were assessed in BALB/c mice immunized with the purified fimbrial
      protein of the Porphyromonas gingivalis strain 381. Groups of mice were immunized
      by gastric intubation of liposomes containing fimbriae and GM-53 on days 0, 1,
      27, and 28. Additional groups of mice were immunized with P. gingivalis fimbriae
      and adjuvant GM-53 in Freund's incomplete adjuvant by subcutaneous injection on
      days 0 and 28. In the latter group of mice, levels of serum IgM anti-fimbria
      antibodies were first detected on day 7, while high levels of serum IgG anti
      fimbria antibodies were seen after secondary immunization. Fimbria-specific spot
      forming cells (SFC) were detected in the spleen, circulating blood mononuclear
      cells (CBMC), and brachial lymph nodes of immunized mice by ELISPOT. Fimbria
      specific IgM SFC appeared by day 5 and antigen-specific IgG SFC were seen later
      in subcutaneously immunized mice. Mice immunized orally exhibited serum anti
      fimbria IgG and IgA antibodies after boosting. Although numerical analysis
      revealed that the numbers of fimbria-specific SFC were generally lower than in
      subcutaneously immunized mice, significant numbers of antigen-specific IgA SFC
      were seen in lamina propria and mesenteric lymph nodes of orally immunized mice.
      In contrast, antigen-specific IgM and IgG SFC were observed mainly in CBMC. The
      route of immunization with fimbriae and GM-53 also influenced the total numbers
      of immunoglobulin-secreting cells. Thus, subcutaneous immunization enhanced the
      total number of IgM and IgG SFC, including fimbria-specific antibody-secreting
      cells in CBMC and the spleen. (ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356428
TI  - Expression of perforin and cytolytic potential of human peripheral blood
      lymphocyte subpopulations.
AB  - To verify the physiological role of the pore-forming protein perforin in vivo,
      its expression in subpopulations of human peripheral blood lymphocytes was
      examined by immunocytochemical staining and their cytolytic potentials compared.
      In addition to NK cells and gamma delta T cells, which uniformly expressed
      abundant perforin in their cytoplasmic granules, only a small subpopulation of
      CD8+ alpha beta T cells contained perforin, namely the CD11b+ subset. However, in
      vitro activation with an anti-CD3 antibody and IL-2 induced perforin expression
      in approximately 50% of the CD8+CD11b- T cells and also in a small subset of CD4+
      T cells. A distribution of perforin in CD8+ and CD4+ T cells, similar to in vitro
      activated T cells, was observed in fresh peripheral blood lymphocytes from
      infectious mononucleosis patients. In all instances, the expression of perforin
      correlated with the cytolytic potential of these subpopulations. The results
      strongly suggest that perforin plays a role in the manifestation of cytotoxic
      activity in vivo.

PMID- 1356429
TI  - Diurnal intraocular pressure variations: an analysis of 690 diurnal curves.
AB  - Out of a total of 2272 diurnal curves (DC) of intraocular pressure (IOP) obtained
      from 1178 patients 690 first curves of the right eye of all patients were
      analysed. For each DC there were 4-6 IOP readings taken between 8 am and 6.30 pm
      of the same day. The patients' diagnosis, age, sex, type of IOP lowering
      medication, diabetes, and the calendar month of the year were recorded. In 40% of
      cases the highest IOP was found at the earliest morning measurement with some 65%
      of peaks occurring before noon. The lowest IOP measurement showed no specific
      predilection for any particular time of the day. These findings were true for all
      diagnosis groups. The mean range of IOP fluctuation during the DC was 5.0 mm Hg
      in normals, 5.8 mm Hg in patients with open angle glaucoma (OAG), and 6.8 mm Hg
      in patients with ocular hypertension (OHT). Patients treated with timolol had a
      lower mean IOP fluctuation range than those on other types of IOP lowering
      treatment. No association was found between all other parameters examined and the
      diurnal IOP distribution.

PMID- 1356431
TI  - Symptoms, disorders and chemistry.

PMID- 1356433
TI  - Characterization of tertiary interactions in a folded protein by NMR methods:
      studies of pH-induced structural changes in human growth hormone.
AB  - The pH-induced conformational changes in human growth hormone (hGH) have been
      studied, using a new quantitative NMR approach that combines 13C labeling of
      specific backbone carbonyl carbons with a complete spectral analysis of the
      corresponding 13C resonances. Thus, a complete analysis of the carbonyl
      resonances of the 26 Leu residues of hGH and their variation with pH provided
      detailed information about the equilibrium folding processes of the protein,
      including information about the kinetics of the folding. By combining this
      information with the pH dependence of readily identifiable 1H resonances, the pH
      induced changes observed in the carbonyl carbon spectra can be associated with
      specific regions in the protein and can be ascribed to a series of localized
      adjustments in the tertiary structure, brought about by changes in the hydrogen
      bond interactions or electrostatic interactions between different residues in the
      globular folded protein. The preexchange lifetimes of these adjustments range
      from a fraction of a millisecond to a few milliseconds.

PMID- 1356432
TI  - Role of monoamine systems in activation of zif268 by cocaine.
AB  - Rapid activation of transcription factor genes is thought to play a key role in
      stimulus-induced neuronal plasticity. To help understand the genomic response
      that may underlie long-term effects of cocaine and amphetamine, we have
      investigated the effect of these agents on Zif268, a transcription regulatory
      factor that is expressed at high levels in brain neurons. Like c-fos, zif268 is
      markedly activated in striatum by cocaine and amphetamine. This response appears
      to involve the dopamine system, since it is abolished by SCH23390, a selective D1
      dopamine receptor antagonist, or by 6-hydroxydopamine lesions. To assess the role
      of other monoamine systems in regulating the expression of these transcription
      factors, we have examined the effects of selective monoamine uptake blockers as
      well as agents that lesion the norepinephrine and serotonin systems. These
      studies indicate that, in addition to the dopamine system, the norepinephrine and
      serotonin systems also play prominent roles in the activation of zif268 and c-fos
      by cocaine and amphetamine.

PMID- 1356430
TI  - Central non-opioid physiological and pathophysiological effects of dynorphin A
      and related peptides.
AB  - Dynorphin A (Dyn A) and related opioid peptides derived from prodynorphin possess
      a high affinity for kappa opioid receptors, but they also bind to other opioid
      receptors (mu and delta) as well as to some non-opioid receptor sites. Although
      the physiological role of these peptides is not well established, recent
      experimental data pinpoint their particular involvement in physiological and
      pathophysiological conditions that relate to algesia, spinal cord injury and
      epilepsy. In this paper, we review data which support the concept that the non
      opioid behavioral effects of Dyn A and related endogenous peptides which are
      observed under these conditions are physiologically and pathophysiologically
      relevant.

PMID- 1356434
TI  - Unfolded proteins stimulate molecular chaperone Hsc70 ATPase by accelerating
      ADP/ATP exchange.
AB  - The mammalian 70-kilodalton heat shock cognate protein (Hsc70) is an abundant,
      cytosolic molecular chaperone whose interactions with protein substrates are
      regulated by ATP hydrolysis. In vitro, purified Hsc70 was found to have a slow,
      intrinsic ATPase activity in the absence of protein substrates. The addition of
      an unfolded protein such as apocytochrome c stimulated ATP hydrolysis 2-3-fold.
      In contrast, the native holoprotein, cytochrome c, did not stimulate the ATPase
      rate, in accord with recent observations that 70-kilodalton heat shock proteins
      interact selectively with unfolded proteins. Stimulation of ATP hydrolysis by
      apocytochrome c was due to an increase in the Vmax, with no effect on the Km for
      ATP. Following hydrolysis of [3H]ATP, a relatively stable [3H]ADP.Hsc70 complex
      was formed. Release of [3H]ADP from Hsc70 was most efficient in the presence of
      other nucleotides such as ADP or ATP, suggesting that ADP release occurs as an
      ADP/ATP exchange reaction. The loss of radiolabeled ADP from Hsc70 in the
      presence of exogenous nucleotides followed first-order kinetics. In the presence
      of nucleotides, apocytochrome c induced a 2-fold increase in the rate of ADP
      release from Hsc70. Moreover, rate constants of the nucleotide exchange reaction
      measured in the absence and presence of apocytochrome c (0.16 and 0.34 min-1,
      respectively) closely matched the kcat values derived from ATP hydrolysis
      measurements (0.15 and 0.38 min-1, respectively). The results suggest that ADP
      release in a rate-limiting step in the Hsc70 ATPase reaction and that unfolded
      proteins stimulate ATP hydrolysis by accelerating the rate of ADP/ATP exchange.

PMID- 1356435
TI  - Inhibition of the chymotrypsin-like activity of the pituitary multicatalytic
      proteinase complex.
AB  - The multicatalytic proteinase complex (MPC), also referred to as proteasome, is a
      large molecular mass intracellular particle (approximately 700 kDa), which
      exhibits three distinct proteolytic activities designated as chymotrypsin-like,
      trypsin-like, and peptidylglutamyl-peptide hydrolyzing (PGPH), all sensitive to
      inhibition by 3,4-dichloroisocoumarin (DCI). The presence of a component
      resistant to inhibition by DCI with an apparent preference toward bonds on the
      carboxyl side of branched-chain amino acids has also been recently established.
      Peptide aldehydes and peptide alpha-keto esters containing a hydrophobic residue
      in the P1 position have been tested as potential inhibitors of the chymotrypsin
      like activity. Three peptide aldehydes (benzyloxycarbonyl)-Leu-Leu-phenylalaninal
      (Z-LLF-CHO), N-acetyl-Leu-Leu-norleucinal (Ac-LLnL-CHO), and N-acetyl-Leu-Leu
      methioninal (Ac-LLM-CHO) were found to be slow-binding reversible inhibitors with
      Ki values of 0.46, 5.7, and 33 microM, respectively. The simplest kinetic model
      for inhibition is consistent with a mechanism involving a slow and reversible
      association of the enzyme with the inhibitor to form a EI complex. The aldehyde
      inhibitors also inhibited the trypsin-like and PGPH activities of the complex
      albeit with much higher Ki values than those for chymotrypsin-like activity. Z
      LLF-CHO, the most selective of the three aldehydes, did not inhibit the PGPH
      activity at concentrations of up to 200 microM and inhibited the trypsin-like
      activity with a Ki approximately 2 orders of magnitude higher than that for the
      chymotrypsin-like activity. The activity of the DCI-resistant component was not
      affected by Z-LLF-CHO.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356436
TI  - Expression of recombinant acetylcholinesterase in a baculovirus system: kinetic
      properties of glutamate 199 mutants.
AB  - The glycophospholipid-linked, amphiphilic form of acetylcholinesterase (AChE)
      from Torpedo californica and the hydrophilic form from mouse were overexpressed
      in Sf9 insect cells using the baculovirus expression system. Recombinant
      baculovirus, constructed by inserting AChE cDNA's into the genome of Autographa
      californica nuclear polyhedrosis virus adjacent to the strong polyhedron
      promoter, yielded recombinant enzyme varying between 0.5 and 3.8 mg/L. The
      recombinant enzyme was glycosylated although it migrated slightly more rapidly in
      SDS gel electrophoresis than enzyme purified from the electric organ of Torpedo.
      Kinetic properties of the recombinant DNA- and tissue-derived enzymes are
      identical. The detailed catalytic properties and susceptibility to inhibitors
      were examined for two enzyme mutations of the glutamate residue N-terminal to the
      active site serine. The Glu199 to Gln mutation shifted both the Km and Kss to
      higher substrate concentrations and resulted in a kcat of 28% of the wild type.
      Mutation of Glu199 to Asp also yielded a reduction in kcat but with no change in
      Km. Substrate inhibition normally apparent in wild-type AChE was eliminated with
      the Asp mutation, suggesting that substrate catalysis and substrate inhibition
      are not directly linked. Both mutations decreased the affinity of reversible
      inhibitors and reduced the rates of phosphorylation and carbamoylation; these
      changes were more striking with the Gln199 mutation. Decarbamoylation rates were
      unaffected by these mutations. Glu199 is the charged residue found deep within
      the active center gorge close to the site of acetylcholine binding, and our
      findings indicate it influences, but is not essential for, efficient catalysis.

PMID- 1356437
TI  - Structure and function of alternative proton-relay mutants of dihydrofolate
      reductase.
AB  - Using site-specific mutagenesis, we have constructed two mutants of Escherichia
      coli dihydrofolate reductase (ecDHFR) to investigate further the function of a
      weakly acidic side chain at position 27 in substrate protonation: Asp27-->Glu
      (D27E) and Asp27-->Cys (D27C). The crystal structure of D27E ecDHFR in a binary
      complex with methotrexate shows that the side-chain oxygen atoms of Glu27 are in
      almost precisely the same location as those of Asp27 in the wild-type enzyme.
      Kinetic evidence indicates that Glu27 can indeed function efficiently in the
      proton relay to dihydrofolate. Even though vertebrate DHFRs all have a glutamic
      acid at the structurally equivalent position, the kinetic properties of Glu27
      ecDHFR more closely resemble those of wild-type bacterial DHFRs than of
      vertebrate DHFRs. The D27C mutation produced an enzyme still capable of relaying
      a proton to dihydrofolate, but with the intrinsic pKa in its pH-activity profiles
      shifted upward to values characteristic of the more basic thiolate group. The
      crystal structure of the binary complex with methotrexate reveals two unexpected
      features: (1) the Cys27 sulfhydryl group does not point toward the pteridine
      binding site, but the side chain of this residue is instead rotated 120 degrees
      to interact with a tyrosine side chain projecting from a neighboring beta-strand;
      (2) a bound ethanol molecule occupies a cavity adjacent to methotrexate. Ethanol
      is a component of the crystallization medium.

PMID- 1356438
TI  - Partial characterization and detergent solubilization of the putative glutathione
      chemoreceptor from hydra.
AB  - Feeding behavior in hydra is initiated by the association of glutathione (GSH)
      with a putative external chemoreceptor. In the present study, the binding of
      [35S]GSH to hydra membranes has been characterized. Nondisplaceable [35S]GSH
      binding which compromised previous analyses [Grosvenor, W., Bellis, S., Kass
      Simon, G., & Rhoads, D. (1992) Biochim. Biophys. Acta (in press)] was eliminated
      by treating membranes with an inhibitor of GSH metabolism, borate in combination
      with L-serine. The specific binding which was not inhibited by borate/serine
      demonstrated many of the characteristics expected of a ligand/receptor
      interaction. The binding was rapid, reversible, and saturable. A Scatchard
      analysis of saturation isotherms indicated a dissociation constant (KD) of 3.4
      microM, a value which is in good agreement with concentrations of glutathione
      which are known to induce feeding behavior. Hydra membranes were detergent
      solubilized with 10 mM 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate
      (CHAPS), 100 mM KCl, and 10% glycerol. The soluble fraction contained 40% of the
      original saturable, reversible GSH binding activity. The KD for GSH binding to
      the solubilized preparation was estimated as 2.7 microM, a valuable which is not
      appreciably different from the KD for binding to intact membranes. The fidelity
      of GSH binding in the solubilized preparation suggests that this preparation will
      be useful in further characterization of the putative glutathione chemoreceptor.

PMID- 1356440
TI  - Proceedings of the 5th Congress of the International Association for Adolescent
      Health. Montreux, July 1991.

PMID- 1356439
TI  - Mechanistic consequences of mutation of the active site nucleophile Glu 358 in
      Agrobacterium beta-glucosidase.
AB  - The replacement of the active site nucleophile Glu 358 in Agrobacterium beta
      glucosidase by Asn and Gln by site-directed mutagenesis results in essentially
      complete inactivation of the enzyme, while replacement by Asp generates a mutant
      with a rate constant for the first step, formation of the glycosylenzyme, some
      2500 times lower than that of the native enzyme. This low activity is shown to be
      a true property of the mutant and not due to contaminating wild-type enzyme by
      active site titration studies and also through studies of its thermal
      denaturation and of the pH dependence of the reaction catalyzed. Binding of
      ground-state inhibitors is affected relatively little by the mutation, while
      binding of transition-state analogues is greatly impaired, consistent with a
      principal role for Glu 358 being in transition-state stabilization, not substrate
      binding. Determination of kinetic parameters for a series of aryl glucosides
      revealed that the glycosylation step is rate determining for all these substrates
      in contrast to the native enzyme, where a switch from rate-limiting glycosylation
      to rate-limiting deglycosylation was observed as substrate reactivity was
      increased. These results coupled with secondary deuterium kinetic isotope effects
      of kH/kD = 1.17 and 1.12 measured for the 2,4-dinitrophenyl and p-nitrophenyl
      glucosides point to a principal role of the nucleophile in stabilizing the
      cationic transition states and in formation of the covalent
      intermediate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356441
TI  - In archaebacteria, there is a doxorubicin efflux pump similar to mammalian P
      glycoprotein.
AB  - We selected for study an anthracycline-resistant mutant from the archaebacteria
      Haloferax volcanii. This resistance was reversed by a Ca(2+)-channel antagonist,
      nifedipine (NDP). This resistance and its reversal by NDP suggest P-glycoprotein
      (Pgp) to be responsible for maintaining an anticancer drug concentration below
      the cytotoxic level. Using rhodamine 123 (RH123) as a substrate for Pgp, we then
      examined whether the resistance to anthracyclines in this bacteria might involve
      a Pgp-like anthracycline efflux pump. RH123 accumulation by the bacteria was
      determined with flow cytometry. A steady-state RH123 accumulation by the
      resistant cells revealed approx. one-fifteenth of that by the wild-type cells,
      which could be remarkably enhanced by NDP. The other modulators of Pgp, diltiazem
      and verapamil, also enhanced RH123 accumulation in resistant cells. The uncoupler
      FCCP completely restored RH123 accumulation in resistant cells to the wild-type
      cell level. RH123 unidirectional efflux from resistant cells after its preloading
      revealed much greater than that from wild-type cells, which was remarkably
      inhibited by FCCP. These confirmed that RH123 low accumulation involves its
      active efflux mechanism. Taken together, the present study indicated that lower
      evolutionary archaebacteria might also express a Pgp-like protein very similar to
      mammalian Pgp.

PMID- 1356442
TI  - v-erb A, nuclear hormone receptors, and oncogenesis.

PMID- 1356443
TI  - Apolipoprotein E1 Lys-146----Glu with type III hyperlipoproteinemia.
AB  - During the screening of samples obtained from 5 individuals with type III
      hyperlipidemia, we identified a variant of apolipoprotein (apo) E which exhibited
      a discrepancy in apo E phenotype showing the E3/E1 isoform on isoelectric
      focusing (IEF) analysis and E3/E3 on gene analysis. Sequence analysis of the DNA
      of the proband that was amplified by PCR and subcloned, revealed a single
      substitution of one lysine (AAG) for one glutamic acid (GAG) at position 146,
      thereby adding two negatively charged units to apo E3. This defect had been
      described only for apo E1 to date (Mann et al. (1989) Clin. Res. 37, 520A
      (abstract)). In this case, PCR-mediated site-directed mutagenesis was used to
      identify the structural alterations forming the abnormal E1 genotype in the
      proband's family. Purified apo E1 Lys-146----Glu showed less than 10% of binding
      activity to apo B, E receptor on human skin fibroblasts compared with apo E3.
      This substitution demonstrates that Lys-146 is essential for the binding of apo E
      to the receptor.

PMID- 1356444
TI  - Characterization of thromboxane A2/prostaglandin H2 receptors and histamine H1
      receptors in cultured guinea-pig tracheal smooth-muscle cells.
AB  - We characterized thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors and
      histamine H1 receptors in Guinea-pig cultured tracheal smooth-muscle cells
      (TSMC). [3H]SQ 29,548 (a TXA2 antagonist)-binding sites were saturable and a high
      affinity with a dissociation constant of 6.2 +/- 0.60 nM (mean +/- S.E.) and a
      receptor density of 46 +/- 4.6 fmol/10(6) cells. [3H]SQ 29548 binding was
      completely inhibited by TXA2 mimetics or antagonists. Intracellular calcium
      concentration ([Ca2+]i) in TSMC was increased with U46619 stimulation and the
      increase was attenuated by TXA2 antagonists, the potencies of which correlated
      with those inhibiting the activities of the [3H]SQ 29548 binding. [3H]Mepyramine
      (a H1 antagonist)-binding sites were also present in TSMC. [3H]Mepyramine had a
      single class of low-affinity-binding sites with a dissociation constant of 2.6 +/
      0.081 microM and a receptor density of 10.6 +/- 0.11 nmol/mg protein.
      [3H]Mepyramine binding in TSMC membrane was inhibited by H1 antagonists, but not
      by H2 antagonists. The inhibition constants of mepyramine in TSMC were 910-times
      lower than those in tracheal membranes. In contrast, the histamine-induced
      increase in [Ca2+]i in TSMC was inhibited in the presence of low concentrations
      of H1 antagonists. All these observations provide evidence that TXA2/PGH2
      receptors, mepyramine-binding sites and/or H1 receptors are expressed in cultured
      TSMC.

PMID- 1356446
TI  - Biopharmacological data and high-performance liquid chromatographic analysis of
      1,4-benzodiazepines in biological fluids: a review.
AB  - A review with 123 references on the analysis of 1,4-benzodiazepines in biological
      samples using HPLC is presented. Some important physico-chemical and
      biopharmacological data for the development of analytical methods are collected.
      Different methods of sample pretreatment, chromatographic conditions and
      detection systems are discussed.

PMID- 1356445
TI  - Reducing-equivalent transfer to the mitochondria during gluconeogenesis and
      ureogenesis in hepatocytes from rats of different thyroid status.
AB  - Isolated hepatocytes from hypothyroid, euthyroid and hyperthyroid rats have been
      employed to investigate the relative importance of reducing-equivalent shuttles
      for the transfer of hydrogen between cytoplasm and mitochondria during
      simultaneous ureogenesis and gluconeogenesis. In cells from hypothyroid animals,
      a 58% depression of glucose formation and 68% reduction in ureogenesis were
      induced by n-butylmalonate, an inhibitor of the malate shuttle. A more reduced
      state of the cytoplasmic compartment and a substantial fall in the concentrations
      of pyruvate, aspartate, alanine and glutamate accompanied this inhibition.
      Preincubation of cells with n-butylmalonate yielded greater inhibitory effects
      than observed in the absence of preincubation. The inhibitory effects on
      gluconeogenesis and ureogenesis were less in cells from euthyroid rats and were
      very much reduced in the case of glucose synthesis and absent in the case of
      ureogenesis, in cells from hyperthyroid rats. It is inferred that both the malate
      aspartate and alpha-glycerophosphate shuttles may function in the transfer of
      reducing equivalents from cytoplasm to mitochondria during ureogenesis in
      hepatocytes. The major inhibition by n-butylmalonate of glucose and urea
      synthesis in hepatocytes from hypothyroid rats is due to the diminished activity
      of the alpha-glycerophosphate shuttle in these cells. Moreover, it follows that
      the NADH arising from the cytoplasmic malate dehydrogenase-catalysed reaction is
      accessible to both the malate-aspartate shuttle and the alpha-glycerophosphate
      shuttle.

PMID- 1356447
TI  - Dialysis as an on-line sample-pretreatment technique for column liquid
      chromatography: influence of experimental variables upon the determination of
      benzodiazepines in human plasma.
AB  - An evaluation is provided of dialysis, coupled on-line to column liquid
      chromatography, as a sample pretreatment procedure for macromolecule-containing
      biological samples. The influence of parameters such as acceptor phase flow rate,
      temperature, hydrophobicity of the analytes, pH, ionic strength and viscosity of
      the sample on the recovery and rate of dialysis is studied. In addition, methods
      to reduce the degree of drug-protein binding and thereby improve the recovery are
      reported. Diazepam, nitrazepam and oxazepam are used as model compounds. A method
      is reported for the fully automated determination of these compounds in human
      plasma using only 100 microliters of sample. Data on repeatability, linearity and
      detectability are given.

PMID- 1356448
TI  - Stability study of ethyl loflazepate in bulk drug, solution and dosage form by
      liquid chromatography.

PMID- 1356450
TI  - Annual congress of the Austrian Society of Hematology and Oncology and the
      Hungarian Societies of Hematology and Oncology. Graz, 27-30 September 1992.
      Abstracts.

PMID- 1356451
TI  - Annual congress of the German Society of Hematology and Oncology. Berlin, 4-7
      October 1992. Abstracts.

PMID- 1356449
TI  - Flow cytometric analysis of P-glycoprotein in normal and leukemic cells.
AB  - Classical multidrug resistance is characterized by overexpression of a membrane
      protein, P-glycoprotein, which acts like a drug-extruding pump, reducing
      accumulation of cytotoxic drugs inside malignant cells. We have developed a
      simple method for detecting an intracellular epitope of P-glycoprotein in normal
      and leukemic cells by the monoclonal antibody JSB-1 and fluorescence-activated
      flow cytometry. Permeabilization of blood and bone marrow cells in unprocessed
      samples is achieved by a commercially available red blood cell lysing solution
      which excellently preserves the light scatter properties of leukocytes. The
      method is suitable for analyzing samples in clinical routine. Lower than 1%
      reactivity was seen in the lymphoid gate of normal peripheral blood and bone
      marrow samples as compared with over 60% of reacting cells in some leukemic
      samples. Twelve patients with acute de novo leukemia were studied at
      presentation, 13 patients at a refractory stage, and 28 in remission. There was a
      positive correlation between the P-glycoprotein and the CD34 expression in acute
      myelogenous leukemia and an association between the P-glycoprotein expression and
      the blast count in both acute myelogenous and lymphatic leukemias.

PMID- 1356453
TI  - Prevalence of venous disease: a community study in west London.
AB  - OBJECTIVE: To find out the prevalence of venous disease in patients aged between
      35 and 70 years. DESIGN: Self-administered questionnaire. SETTING: Community
      study in west London, England. SUBJECTS: A random sample of 2,103 patients aged
      between 35 and 70 years who were registered with three general practices.
      RESULTS: 1,338 (64%) subjects filled in the questionnaires. Of these, 323/1,303
      (25%) said that they had varicose veins, 81/1,338 (6%) had a deep vein thrombosis
      or pulmonary embolism, and 52/1,336 (5%) said that they had had phlebitis. In
      addition, 94/1,326 (7%) had worn support stockings, and 84/1,304 (6%) had been
      treated with anticoagulants at some time; 31% of responders reported that they
      had had some form of venous disease. CONCLUSIONS: Increased age and female sex
      were independent risk factors for varicose veins and phlebitis. Thrombosis and
      pulmonary embolism were both significantly associated with the presence of
      diabetes, female sex, and increased age. The facts that a quarter of the sample
      had varicose veins, and that nearly a third had had venous disease of some kind
      at some time, suggest that venous disease may place a heavier burden on health
      resources than had been realised.

PMID- 1356452
TI  - Nuclear morphometry and DNA flow cytometry as prognostic factors in female breast
      cancer.
AB  - OBJECTIVE: To evaluate the predictive value of traditional prognostic factors,
      nuclear morphometry, and flow cytometric data in invasive breast cancer. DESIGN:
      Open study. SETTING: One university hospital in Finland. SUBJECTS: 248 women with
      invasive breast cancer followed up for more than 11 years. MAIN OUTCOME MEASURES:
      Univariate and multivariate analysis of factors thought to indicate prognosis.
      RESULTS: Diameter of the tumour, lymph node status, S phase fraction. DNA index,
      the age of the patient, and the SD of nuclear perimeter were significant
      independent predictors in the whole series in a multivariate analysis. In node
      negative patients the SED of the nuclear perimeter and diameter of the tumour had
      independent prognostic value, whereas in node positive patients diameter of the
      tumour and the S phase fraction were independently related to survival.
      CONCLUSIONS: Diameter of the tumour is an important prognostic factor in breast
      carcinomas. Histoquantitative methods are superior to conventional histological
      techniques for the prediction of outcome in women with breast cancer.

PMID- 1356454
TI  - A questionnaire to assess risk factors, quality of life, and use of health
      resources in patients with venous disease.
AB  - OBJECTIVE: To test the accuracy and usefulness of a questionnaire to assess risk
      factors and symptoms of venous disease, quality of life, and dependence on health
      and social services. DESIGN: Case-control study. SETTING: Multicentre study in
      three general practices. SUBJECTS: Patients drawn from a larger investigation of
      prevalence of venous disease. RESULTS: Patients who had venous disease were
      taller and heavier and had spent more time standing at work than those who did
      not. It was strongly associated with both number of pregnancies and number of
      children. There were weak but not significant associations with the wearing of a
      corset, constipation, and a family history of venous problems. CONCLUSIONS: The
      questionnaire was able to pick out recognised risk factors, and is suitable for
      use in studies of patients with venous disorders. It may also provide information
      about factors that have not yet been accepted. The case-control study is an
      appropriate way of assessing not only risk factors, but also signs and symptoms,
      quality of life, and use of health resources in patients with venous disease.

PMID- 1356455
TI  - The influence of biliary obstruction and sepsis on reticuloendothelial function
      in rats.
AB  - Obstructive jaundice is frequently associated with septic complications and renal
      impairment. The present study was performed in order to evaluate
      reticuloendothelial system (RES) function in obstructive jaundice and the
      influence of a septic challenge. Male Sprague-Dawley rats were allocated into
      four groups (laparotomy alone, caecal ligation and puncture (CLP), ligation of
      the common bile duct (CBD) alone and CBD+CLP, respectively). Mortality, blood
      clearance and organ distribution of 125I labelled Escherichia coli were
      determined. Mortality in sepsis (CLP) significantly increased in jaundiced
      animals (p less than 0.033). Blood clearance of radiolabelled E. coli was
      significantly impaired in both jaundiced groups. In jaundiced animals, hepatic
      localisation and renal uptake of E. coli significantly increased (p less than
      0.001), while radioactive counts in bile significantly decreased (p less than
      0.01). Changes in organ distribution of bacteria did not depend on alterations in
      blood flow. Thus, RES function was impaired in jaundiced animals and mortality
      increased in a concomitant septic challenge in jaundiced animals.

PMID- 1356456
TI  - Vascular clearance of particulate substances: function of the reticuloendothelial
      system or measurement of liver blood flow? Invited commentary.

PMID- 1356457
TI  - Scoring systems for predicting outcome in acute hemorrhagic necrotizing
      pancreatitis.
AB  - Five scoring systems for predicting the severity and outcome of acute
      haemorrhagic necrotizing pancreatitis were retrospectively evaluated in 39
      patients. The respective scores were Ranson, Imrie, APACHE II, multiple organ
      failure (MOF) and Sepsis Sensitivity Score (SSS). Twenty-two (56%) of the
      patients died. The survivors were significantly younger than the non-survivors,
      68% of whom died within 3 weeks of admission to the intensive care unit. Stay in
      the unit was significantly longer in the former group. Sensitivity in prediction
      of death was best with APACHE II score greater than 9 (96%) and Ranson score
      greater than or equal to 3 (95%). Of the five scores, MOF greater than or equal
      to 4 gave the best equilibration between sensitivity (73%) and specificity (76%)
      and the strongest prediction of lethal outcome (80%). Although the independent
      factor age had low sensitivity (55%), it showed the highest values for
      specificity (88%) and prediction of death (86%). APACHE II scoring is concluded
      to be best for grading the severity of disease on admission to intensive care,
      while the MOF score is best for monitoring the degree of organ dysfunction and
      the intensity of supportive treatment.

PMID- 1356458
TI  - Tumour antigens CA 195 and CA 19-9 in pancreatic juice and serum for the
      diagnosis of pancreatic carcinoma.
AB  - OBJECTIVE: To see if tumour associated antigens CA 195 and CA 19-9 were able to
      differentiate between patients with pancreatic carcinoma, and those with chronic
      pancreatitis or stones in the common bile duct. DESIGN: Prospective, open,
      clinical study. SETTING: 47 patients with histologically confirmed pancreatic
      adenocarcinoma, 38 with chronic pancreatitis diagnosed by endoscopic retrograde
      cholangiopancreatography (ERCP), and 26 with stones in the common bile duct
      diagnosed and treated by ERCP. INTERVENTIONS: Samples of serum taken from all
      patients just before ERCP, and samples of pancreatic juice obtained from 18, 11,
      and 12 patients, respectively during ERCP. RESULTS: Assay of the two tumour
      markers in pancreatic juice failed to differentiate between patients with benign
      and malignant disease. When assayed in serum, however, CA 195 detected those with
      carcinoma with a sensitivity of 72% and a specificity of 92%, and CA 19-9 with a
      sensitivity of 81% and a specificity of 88%. The patients with unresectable
      tumours had significantly higher concentrations of both markers in serum than
      patients with resectable tumours (p less than 0.05). CONCLUSIONS: CA 195 and CA
      19-9 concentrations in serum are equally successful in differentiating between
      benign and malignant pancreatic disease. Assay of markers in pancreatic juice
      does not provide useful diagnostic information.

PMID- 1356459
TI  - Fosfomycin/metronidazole compared with doxycycline/metronidazole for the
      prophylaxis of infection after elective colorectal surgery. A randomised double
      blind multicentre trial in 517 patients.
AB  - OBJECTIVE: To find out if fosfomycin together with metronidazole was any better
      than doxycycline with metronidazole for the prophylaxis of infection before
      elective colorectal operations. DESIGN: Multicentre, double blind, random control
      trial. SETTING: Nine Swedish hospitals. SUBJECTS-559 patients admitted for
      elective colorectal operations. INTERVENTIONS: Fosfomycin 8 g and metronidazole 1
      g before operation and fosfomycin 8 g eight hours afterwards, or doxycycline 400
      mg and metronidazole 1 g before operation, and placebo eight hours afterwards.
      MAIN OUTCOME MEASURES: Incidence of all types of infection, mortality, and side
      effects. RESULTS: There were no significant differences between the groups for
      any of the outcome measures studied, the overall abdominal infection rates
      (wound, deep, and septicaemia) being 4.6% and 7.4%, and the remote infection
      rates (pneumonia, urinary tract, and central venous line) 15.1% and 12.8%,
      respectively. Of the predictors studied, only duration of operation was
      significantly related to risk of infection. CONCLUSION: The combination of
      fosfomycin and metronidazole was as safe and effective as that of doxycycline and
      metronidazole in preventing infections after elective colorectal operations.

PMID- 1356460
TI  - Ischemic colitis complicating imipramine overdose and alcohol ingestion. Case
      report.
AB  - Patients on antidepressant medication are instructed to avoid alcohol because of
      possible additive effects on cognitive function. An unusual case of colonic
      gangrene following overdose of imipramine and alcohol is presented. The patient
      recovered.

PMID- 1356461
TI  - Misleading cause of acute arterial insufficiency: ergotamine intoxication. Case
      report.
AB  - In a woman arteriographically indicated spasm of the iliac, femoral and popliteal
      arteries did not respond to intra-arterial tolazoline. At operation groin
      pulsations were normal. Bilateral lumbar sympathectomy was performed.
      Subsequently it emerged that she had been using ergotamine. Surgery could have
      been avoided if nitroprusside had been given.

PMID- 1356462
TI  - Mammary arteritis mimicking cancer. Case report.
AB  - Giant cell arteritis and polyarteritis nodosa are systemic diseases which rarely
      involve the breasts. Two cases are reported in which breast masses, clinically
      suspected to be malignant, were found to be isolated vasculitis--bilateral giant
      cell mammary arteritis in a 67-year-old woman and isolated mammary polyarteritis
      nodosa in a 45-year-old woman. Vasculitis should be considered in the
      differential diagnosis of breast masses.

PMID- 1356463
TI  - Mesenteric vein thrombosis after injection sclerotherapy for oesophageal varices.
      Case report.

PMID- 1356464
TI  - Gene expression of insulin-like growth factor-I and IGF-I receptor during wound
      healing in rats.
AB  - OBJECTIVE: To measure the time course of changes in the concentrations of insulin
      like growth factor-I (IGF-I), IGF-I messenger RNA (mRNA), and IGF-I receptor mRNA
      during wound healing. DESIGN: Open experimental study. MATERIAL: 40 male Sprague
      Dawley rats, each weighing 300 g. INTERVENTION: Stainless steel wire mesh
      cylinders implanted in the subcutaneous tissue of the back. Five rats killed at
      each time point (1.5, 2, 3, 4, 5, 7, 11, and 18 weeks). MAIN OUTCOME MEASURES:
      Wet weight and concentrations of IGF-I mRNA, and IGF-I receptor mRNA of
      granulation tissue, and concentration of IGF-I in wound fluid. RESULTS: The wet
      weight of granulation tissue increased significantly between week 1.5 and weeks 4
      5, and then decreased. IGF-I mRNA concentration (amol/microgram DNA) increased
      significantly (threefold) between week 1.5 and weeks 3-5, and decreased between
      weeks 5 and 7. The concentration of IGF-I receptor RNA remained constant
      throughout the study, and the concentration of IGF-I in wound fluid remained
      constant until week 8 and then increased to a higher level at weeks 11-18.
      CONCLUSION: There is a transient rise in the gene expression of IGF-I but not of
      IGF-I receptor mRNA during wound healing.

PMID- 1356465
TI  - Connective tissue repair in zinc deficiency. An ultrastructural morphometric
      study in perforated mesentery in rats.
AB  - OBJECTIVE: To quantify measures of healing in zinc-deficient and healthy rats.
      DESIGN: Randomized study. MATERIAL: 30 male Sprague-Dawley rats. INTERVENTIONS:
      Zinc deficiency was induced in half the rats. All rats underwent laparotomy and
      standard perforations were made in the small intestinal mesentery with a scalpel.
      At 1, 3, 5, 7 and 10 days after operation 6 rats were killed by overdose of
      anaesthetic agents and the specimens of the mesentery were fixed. MAIN OUTCOME
      MEASURES: Measurement of cellular volume density, surface density of the rough
      endoplasmic reticulum, and surface density of the plasma membrane. RESULTS:
      Perforations started to close on day 4, and most were closed by day 10. Cellular
      volume density reached its peak between days 3 and 5, as did surface density of
      rough endoplasmic reticulum. There were no significant differences between the
      two groups for either measurement. The surface density of the rough endoplasmic
      reticulum, however, was significantly higher in controls than in zinc deficient
      animals on days 3-10 (p less than 0.001). The surface density of the plasma
      membrane was significantly higher in zinc-deficient animals on days 1-3 (p less
      than 0.04), and in control animals on days 5-10 (p less than 0.01). CONCLUSIONS:
      Protein synthesis and formation of scar tissue were slightly lower in the zinc
      deficient animals, and the higher plasma membrane surface density implies that
      contraction may be an important part of healing in the small intestinal mesentery
      in rats.

PMID- 1356466
TI  - Comparison between sterile saline and tap water for the cleaning of acute
      traumatic soft tissue wounds.
AB  - OBJECTIVE: To find out if there were any differences in infection rates if acute
      traumatic soft tissue wounds were cleaned with tap water instead of sterile
      saline. DESIGN: Randomised study. SETTING: Emergency department at one city
      hospital. SUBJECTS: 705 consecutive patient with soft tissue wounds less than six
      hours old that did not penetrate a viscus, cavity, or joint and could be treated
      by primary suture. INTERVENTIONS: Randomly allocated to have the wound cleaned
      with either sterile saline or tap water in addition to debridement. MAIN OUTCOME
      MEASURE: Rate of wound infection, the presence of which was indicated by pus in
      the wound and prolonged healing. RESULTS: The infection rate in wounds cleaned
      with sterile saline was 10.3% compared with 5.4% in wounds cleaned with tap water
      (p less than 0.05). Infected wounds were significantly larger than uninfected
      ones (p less than 0.05) and more likely to be located on a lower extremity (p
      less than 0.05). There were no microbiological differences between the two
      groups, and no bacterial species grown from tap water was subsequently grown from
      an infected wound. CONCLUSION: Sterile saline should be replaced by tap water for
      the cleaning of acute traumatic superficial soft tissue wounds.

PMID- 1356467
TI  - Morbidity and short term results in a randomised trial of open compared with
      closed treatment of chronic pilonidal sinus.
AB  - OBJECTIVE: To evaluate the morbidity and short term results after open compared
      with closed treatment of chronic pilonidal sinus. DESIGN: Randomised control
      trial. SUBJECTS: 120 of 164 patients with chronic pilonidal sinus treated between
      April 1987 and April 1989. INTERVENTIONS: 60 patients were treated by excision
      and primary suture, and 60 by excision and open packing. MAIN OUTCOME MEASURES:
      Incidence of early complications (bleeding that needed treatment, wound
      breakdown, infection, haematoma, or wound pain), number of postoperative visits
      required, and length of sick leave taken. RESULTS: Those patients who underwent
      excision and suture had slightly but not significantly fewer early complications
      (16/60, 27%, compared with 23/60, 38%). Most of the early complications were the
      result of infection (8, 13% compared with 18, 30%, respectively). They also
      required fewer followup visits and less sick leave, and their wounds healed more
      quickly. At one year the numbers of late complications were 19 (32%) and 14
      (23%), respectively. CONCLUSION: Excision and primary closure of chronic
      pilonidal sinus causes less morbidity and is more cost effective than excision
      and open packing. We plan a three year follow-up to see if these results are
      maintained.

PMID- 1356468
TI  - Long term results after Nissen fundoplication and Belsey Mark IV operation in
      patients with reflux oesophagitis and stricture.
AB  - This retrospective study was undertaken to compare long term results of Nissen
      fundoplication and the Belsey Mark IV repair in patients with reflux oesophagitis
      and stricture between 1972 and 1987. 105 patients were operated on for reflux
      oesophagitis, and 43 of the patients had stricture. There was one postoperative
      death (after a Belsey Mark IV repair). The cumulative recurrence rate after the
      Nissen operation was 9%, all recurrences of oesophagitis occurring within the
      first two years. The cumulative recurrence after the Belsey repair was 37%. Only
      15 of 32 patients treated with Nissen fundoplication for stricture needed
      dilatation after operation, and then only during the first two years. "Gas-bloat"
      occurred in 18% of the patients treated with Nissen fundoplication. We conclude
      that the Nissen fundoplication is a good operation for patients with severe
      reflux oesophagitis and for those with peptic strictures of the oesophagus. The
      Belsey Mark IV repair, however, cannot be recommended for patients with
      strictures.

PMID- 1356470
TI  - Diagnostic accuracy of ultrasonography and C reactive protein concentration in
      acute cholecystitis: a prospective clinical study.
AB  - OBJECTIVE: To assess the value of ultrasonography together with C reactive
      protein concentration in predicting which patients with acute cholecystitis
      require immediate operation. DESIGN: Prospective study. SETTING: Oulu University
      Hospital, Finland. SUBJECTS: 129 consecutive patients admitted with suspected
      acute cholecystitis 1988-89. MAIN OUTCOME MEASURES: Correlation of
      ultrasonographic findings and C reactive protein concentrations with histological
      findings. RESULTS: Ultrasonography correctly classified 86 of 108 patients with
      acute cholecystitis (79%). When the findings were combined with those of
      increased concentrations of C reactive protein the accuracy rose to 105 of 108
      (97%). Large increases in C reactive protein concentrations were associated with
      both infected bile and gangrene of the gall bladder. CONCLUSIONS: The combination
      of ultrasonography and measurement of C reactive protein concentration is
      recommended in the routine investigation of all patients with suspected acute
      cholecystitis. Serum C reactive protein concentrations should be monitored
      regularly to select those patients who require emergency operation.

PMID- 1356469
TI  - Development of stress ulcers assessed by gastric electrical potential difference,
      pH of gastric juice, and endoscopy in patients in the intensive care unit.
AB  - OBJECTIVE: To assess measurement of gastric electrical potential difference, pH
      of gastric mucosa, and endoscopic findings in patients in intensive care units
      who are at risk of developing stress ulcers. DESIGN: Open comparison with age-
      and sex-matched control subjects. SETTING: Herlev Hospital, Denmark. SUBJECTS:
      Sixteen consecutive patients with no history of gastrointestinal haemorrhage,
      coagulopathy, or ulcer disease who had been admitted to the intensive care unit,
      and 16 age- and sex-matched outpatients with normal endoscopic findings.
      INTERVENTIONS: Upper gastrointestinal endoscopy, during which any lesions that
      were found were scored according to severity, the gastric potential difference,
      and the pH of gastric juice were measured. OUTCOME MEASURES: Correlation between
      the incidence of stress ulceration found at endoscopy, gastric potential
      difference, and gastric pH. RESULTS: Gastric potential difference was
      significantly reduced and gastric pH significantly increased in the patients in
      the intensive care unit (p less than 0.05 in both cases), all of whom had stress
      ulcers in more than one gastric segment. Nine of the patients had gastric pH
      readings of greater than 4. CONCLUSION: Gastric electrical potential difference
      may be useful measurement for the assessment of stress ulceration in patients in
      intensive care units.

PMID- 1356471
TI  - Blood transfusion and recurrence of colorectal cancer.
AB  - Because perioperative blood transfusions have been shown to have an impaired
      effect on survival in patients with colorectal cancer, we examined
      retrospectively the records of 882 patients who had undergone curative
      operations: 170 patients had distant metastases at the time of operation. Of the
      499 patients with colonic cancer 332 (67%) had received perioperative blood
      transfusions. The corresponding figure for the 213 patients with rectal cancer
      was 190 (89%). Colonic tumors recurred in 45% of the patients who received blood
      transfusions and in 39% of those who did not. Corresponding figures for tumors in
      the rectum were 54% and 55%. When dividing the patients with colonic cancer into
      different subgroups according to Dukes' grade we found differences in survival
      rates. The poorer survival for transfused patients was, however, only significant
      for those with Dukes' A tumors (p less than 0.05). This difference disappeared
      when the influence of age was eliminated. The estimated risk ratio of recurrence
      and death was 1.23 with the 95% confidence interval (0.99, 1.53) when taking
      Dukes' grade, current age and localization into account. Blood transfusion should
      be avoided if possible until adequate prospective studies have been carried out.

PMID- 1356472
TI  - Bleeding from an epiphrenic oesophageal diverticulum.
AB  - A 49-year-old woman with a 2-month history of mild dysphagia and three episodes
      of haematemesis was found at endoscopy and barium swallow to have an epiphrenic
      oesophageal diverticulum containing an ulcerating crypt, but no ectopic gastric
      epithelium. Diverticulectomy and lower oesophageal myotomy gave a good result.

PMID- 1356473
TI  - Massive gastrointestinal bleeding secondary to intestinal varices.

PMID- 1356474
TI  - Rectal leiomyosarcoma: acute presentation after local injury.
AB  - Rectal leiomyosarcoma is rare, often large and found in the distal third of the
      rectum. Most symptoms differ from those of an adenocarcinoma. Staging is
      difficult and should include tumour size, necrosis, cellularity, number of
      mitoses and anaplasia. Abdominoperineal excision (APE) remains the only effective
      treatment. A 66 year old asymptomatic female presented with painless rectal
      bleeding after a fall. Digital examination and proctoscopy revealed a mass on the
      posterior rectal wall. Pelvic ultrasonography, arteriography and CT-Scan showed a
      huge retro-rectal lesion. Following APE, histopathology confirmed a
      leiomyosarcoma. No adjuvant therapy was given; there is no recurrence 4 years
      later.

PMID- 1356475
TI  - Inflammatory fibroid polyp that caused intussusception of the ileum.

PMID- 1356476
TI  - Validation of subjective measures of fatigue after elective operations.
AB  - OBJECTIVE: To find out if it was possible to evaluate postoperative fatigue by
      questionnaire. DESIGN: Open study. SETTING: University hospital. SUBJECTS: 23
      patients about to undergo elective general surgical operations. INTERVENTIONS: A
      questionnaire was filled in before, and 2-46 days after, operation. MAIN OUTCOME
      MEASURES: Six measures of fatigue were derived from the questionnaire and
      validated objectively with changes in body weight, exercise tolerance (n = 10),
      or grip strength (n = 21). RESULTS: The six measures all showed a significant
      increase after operation. The changes in fatigue correlated well, but there were
      differences in sensitivity to changes in perceived weakness compared with
      perceived tiredness. Each measure correlated significantly with either body
      weight, exercise tolerance or grip strength. CONCLUSION: Questionnaires can
      provide reliable results in the assessment of postoperative fatigue.

PMID- 1356477
TI  - Bone mineral density in patients with familial hypocalciuric hypercalcaemia
      (FHH).
AB  - OBJECTIVE: To find out whether chronic hypercalcaemia and excessive secretion of
      parathyroid hormone (PTH) is associated with skeletal demineralisation in
      familial hypocalciuric hypercalcaemia (FHH). DESIGN: Open study. SETTING:
      Huddinge University Hospital, Sweden. SUBJECTS: Nine affected and three
      unaffected members of two kindreds with FHH, and 12 age- and sex-matched
      controls. INTERVENTIONS: Measurement of bone mineral density (g/cm2) in the
      proximal femur and lumbar spine by dual photon absorptiometry, and of bone
      mineral content in the distal radius and midradius (g/cm) by single photon
      absorptiometry. Measurement of serum concentrations of PTH, total and ionised
      calcium, phosphate, and magnesium, and alkaline phosphatase activity, and 24 hour
      urinary calcium excretion were also made. RESULTS: Bone mineral density was
      significantly higher in Wards's triangle of the femur (p < 0.05) in the members
      of families with FHH than in control subjects. In the other parts of the femur
      and in the lumbar vertebrae it was slightly but not significantly higher, as was
      the bone mineral content of the distal radius and midradius. Family members with
      FHH all had increased total and ionised serum calcium concentrations, except for
      the index case in one of the families who developed hypoparathyroidism
      postoperatively. Twenty-four urinary calcium excretion was less than 5 mmol (the
      upper limit of the reference range for FHH) in all the affected patients.
      CONCLUSION: Chronic hypercalcaemia in affected members of families with FHH is
      not the result of an increase rate of bone mineralisation, because they have
      normal bone mass. They seem to be relatively insensitive to the deleterious
      effects of PTH on bone mineral state, because raised concentrations of PTH were
      not associated with reduced bone mass.

PMID- 1356478
TI  - Open management with mesh and zipper of patients with intra-abdominal abscesses
      or diffuse peritonitis.
AB  - OBJECTIVE: To evaluate the open management of intra-abdominal abscesses and
      persistent peritonitis by the "mesh and zipper" technique, and to assess the
      predictive value of the APACHE II score. DESIGN: Prospective open study.
      SUBJECTS: 21 consecutive patients with life-threatening peritonitis.
      INTERVENTIONS: Insertion of mesh and zipper and lavage once or twice daily with
      several litres of warmed saline. MAIN OUTCOME MEASURE: Mortality. RESULTS: Eleven
      of the 21 patients died (52%). The APACHE II score accurately predicted outcome,
      in that no patient who scored less than 20 points died, and no patient who scored
      more than 26 points lived. CONCLUSION: The mesh and zipper technique with daily
      intraperitoneal lavage is effective in the treatment of life-threatening
      peritonitis and the APACHE II score is an accurate predictor of survival.

PMID- 1356479
TI  - Erythromycin accelerates delayed gastric emptying of solids in patients after
      truncal vagotomy and pyloroplasty.
AB  - OBJECTIVE: To find out if erythromycin (a motilin agonist) accelerated gastric
      emptying after vagotomy and in normal subjects. DESIGN: Double blind controlled
      study. SETTING: Two referral centres. SUBJECTS: 15 patients who had previously
      undergone vagotomy and who did (n = 8) or did not (n = 7) have symptoms of
      gastric stasis and 10 normal controls. INTERVENTIONS: A standard meal containing
      185 x 10(5) Bq -99mTc was eaten after either erythromycin 200 mg or 40 ml placebo
      (normal saline) had been given intravenously. Subjects were then scanned by gamma
      camera. MAIN OUTCOME MEASURES: Measurement of: the length of time from completion
      of the meal to the onset of gastric emptying; the length of time from completion
      of the meal until half of the meal had left the stomach; the length of the time
      from the onset of gastric emptying until half of the meal had left the stomach;
      and the percentage of the meal that was left in the stomach at 60 and 120 min
      after the end of the meal. RESULTS: Gastric emptying was significantly delayed in
      those patients with symptoms compared with normal subjects and patients without
      symptoms. Erythromycin accelerated the first two phases of gastric emptying in
      all patients and normal subjects, but did not affect the length of time from the
      onset of gastric emptying until half the meal had left the stomach. CONCLUSION:
      Erythromycin could be a useful gastrokinetic agent in patients with symptoms of
      gastric stasis after vagotomy.

PMID- 1356480
TI  - R2 compared with R1 resection for gastric cancer: morbidity and mortality in a
      prospective, randomised trial.
AB  - OBJECTIVE: To compare the postoperative course of patients in the Dutch
      nationwide randomised trial of R1 (conventional) compared with R2 resection
      (including extended lymph node dissection) in the treatment of gastric cancer.
      DESIGN: Prospective randomised controlled trial. SETTING: National multicentre
      trial with 72 participating hospitals in The Netherlands. SUBJECTS: 192 patients
      who were operated on between August 1989 and May 1990. INTERVENTIONS: 96 patients
      were randomised for a R1, and 96 for a R2 resection. MAIN OUTCOME MEASURES:
      Morbidity and mortality among 131 patients (64 R1 and 67 R2) for whom the
      resection was performed with curative intent. RESULTS: The groups were comparable
      for age, sex, type of resection, site of tumour and depth of invasion.
      Complications developed in 23 R1 (36%) and in 29 R2 patients (43%). Seven
      patients died in the postoperative period. Median hospital stay was significantly
      longer after R2 (18 days, range 7-122) than after R1 resection (15 days, range 2
      63) (p < 0.05). Morbidity and mortality among the patients whose R2 resection was
      done by the Japanese instructor (n = 34) did not differ significantly from those
      among patients operated on by the Dutch supervisors (n = 33), but those operated
      on by the Japanese instructor stayed in hospital significantly longer (20
      compared with 16 days, p < 0.05). CONCLUSIONS: If R2 resections are carried out
      by properly trained surgeons under supervision, they can be done safely. The
      reported high morbidity after R2 resection in Western countries seems to result
      from a lack of proper instruction and quality control.

PMID- 1356481
TI  - Adverse effects of perioperative blood transfusion in patients with colorectal
      cancer.
AB  - OBJECTIVE: To assess the effects of perioperative blood transfusion on cancer
      related survival and infective complications after radical operations for
      colorectal cancer. DESIGN: Retrospective study. SETTING: District hospital in
      Sweden. SUBJECTS: 217 patients who fulfilled the criteria for inclusion, out of
      392 consecutive patients operated on for colorectal cancer between 1975 and 1979.
      MAIN OUTCOME MEASURES: Morbidity and cancer related mortality depending on
      whether blood was transfused and, if so, how much. RESULTS: Dukes' stage (p <
      0.001), rectal tumours (p < 0.05) and the number of units transfused (p < 0.05)
      were significantly associated with cancer related mortality. Patients with rectal
      cancer transfused with 1-2 units had significantly better survival than those
      transfused with more than 4 units (p < 0.05), but this was not the case for
      colonic tumours. There was no significant association between blood transfusion
      and the incidence of infective complications. CONCLUSION: Though there seems to
      be an association between the number of units of blood transfused and cancer
      related survival in patients with rectal cancer, this does not necessarily imply
      causation. We recommend that until this is clarified by large, prospective
      investigations, autologous blood should be used whenever possible, and
      unnecessary blood transfusion should be avoided.

PMID- 1356482
TI  - Derotation of the mid gut for the treatment of chronic duodenal ileus. Surgical
      technique.

PMID- 1356483
TI  - Colonic obstruction caused by endoscopic percutaneous gastrostomy.

PMID- 1356485
TI  - Eosinophilic gastroenteritis: report of two cases and comment on the literature.
AB  - Two cases of eosinophilic gastroenteritis (EGE) are reported. One recovered
      spontaneously, the other relapsed after bowel resection. Comments outline the
      immunological processes. They relate EGE to the hypereosinophilic syndrome (HES)
      and other collagenous diseases. Bowel resection is discouraged in favor of more
      conservative treatment.

PMID- 1356484
TI  - Acute compartment syndrome: for how long can muscle tolerate increased tissue
      pressure?

PMID- 1356487
TI  - Fatal postoperative gastric necrosis caused by Clostridium perfringens.

PMID- 1356486
TI  - Treatment of high output enterocutaneous fistulas with a somatostatin analogue
      and famotidine.

PMID- 1356488
TI  - Multicystic peritoneal mesothelioma: not a benign condition.

PMID- 1356489
TI  - Experimental and clinical aspects of surfactant replacement. Papers from the 6th
      European Workshop on Surfactant Replacement. Heviz, Hungary, May 10-12, 1991.

PMID- 1356490
TI  - Clinical predictors of relapse following neuroleptic withdrawal.
AB  - The validity of previously hypothesized predictors of elapse following
      neuroleptic discontinuation was examined. One hundred sixty-two outpatients, with
      either Research Diagnostic Criteria schizophrenia or schizoaffective disorder,
      were discontinued from neuroleptic medication for a 28-day period or until judged
      to be relapsed. Pre-discontinuation neuroleptic dosage level, the severity of
      psychotic symptoms, and the presence of dyskinetic movements prior to neuroleptic
      discontinuation were the predictor variables. Of the 162 patients, 62.7% did not
      relapse during the study period. There were no differences in the survival rates
      between the patients withdrawn from oral versus depot neuroleptics. Neuroleptic
      dosage, but not severity of psychotic symptoms or dyskinetic movements, predicted
      relapse. These results support the hypothesis that pre-withdrawal neuroleptic
      dosage level predicts relapse, but fail to validate either severity of psychotic
      symptoms or presence of dyskinetic movements as predictors of relapse.

PMID- 1356491
TI  - MDMA (Ecstasy) precipitation of panic disorder.
AB  - The authors describe three patients whose panic disorder began during
      recreational use of MDMA (Ecstasy) and was subsequently complicated by
      agoraphobic avoidance that continued autonomously after cessation of the drug.
      Their panic disorder responded well to serotoninergic antidepressant drugs.
      Theoretical and practical implications are discussed.

PMID- 1356492
TI  - Impaired detoxification of reactive oxygen and consequent oxidative stress in
      experimentally cryptorchid rat testis.
AB  - The effect of experimental cryptorchidism on the level of oxidative stress and
      antioxidant functions in rat testis was studied. Adult male Sprague-Dawley rats
      were rendered unilaterally cryptorchid (by suturing one testis to the abdominal
      wall) and killed 1, 3, or 7 days after the operation. As an indicator of
      oxidative stress, lipid peroxidation was measured by the diene conjugation method
      in testis homogenates. The activities of the antioxidant enzymes were determined
      either in the 10,000 x g supernatant fraction (glutathione [GSH] peroxidase, GSH
      transferase, hexose monophosphate shunt) or in crude testis homogenates
      (superoxide dismutase, catalase). An expected reduction (48%) in weight of the
      abdominal testes was evident by postoperative Day 7. The catalytic activities per
      testis of superoxide dismutase (Cu/Zn form) and catalase were found to decrease
      in cryptorchidism. The effect was seen on the first postoperative day and was
      most profound on Day 7 after surgery. The principal antioxidant enzyme,
      superoxide dismutase, was most sensitive to cryptorchidism, the activity in the
      abdominal testes being 74% or 85% (per gram of tissue or per whole testis,
      respectively; p less than 0.01). After impairment of the reactive oxygen
      detoxifying capacity, lipid peroxidation was increased in the abdominal testis by
      46% (p less than 0.01) on postoperative Day 7. Slight concomitant increases were
      detected in the activities of GSH-peroxidase (p less than 0.01), GSH-transferase
      (p less than 0.001), and the hexose monophosphate shunt (p less than 0.001). This
      effect was seen only when calculated per gram of tissue, not per whole
      testis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356494
TI  - Alcohol and other drug abuse: changing lives through research and treatment.
      Proceedings of the 4th National Conference on Health Care for the Poor and
      Underserved. Nashville, Tennessee, October 1991.

PMID- 1356493
TI  - [Applications of positron emission tomography (PET) to the measurement of
      regional cerebral pharmacokinetics].
AB  - Positron emission tomography (PET) has not only a variety of applications to
      functional diagnostics using methods of nuclear medicine and for the
      investigation of pathophysiological processes, it also offers new possibilities
      for pharmacology. As PET is able to quantitatively record "from outside" the
      regional concentration of a positron emitter in a living primate, the
      distribution and kinetics of a labelled drug at the site of action can be
      determined non-invasively. This is always the case if the research substance can
      be labelled practically carrier-free with a short-lived positron emitter such as
      11C (T1/2 = 20 min) or if applicable 18F (T1/2 = 110 min). The quantities applied
      in this case are so small that pharmacodynamic effects do not occur. Therefore,
      this method is particularly suitable for measuring in vivo the regional cerebral
      pharmacokinetics of centrally acting drugs in humans.

PMID- 1356495
TI  - Pharmacotherapies for treatment of opioid dependence.

PMID- 1356496
TI  - Drug induced impairment of performance.

PMID- 1356497
TI  - IV International Symposium on Blood Substitutes. Montreal, Canada, 1991.

PMID- 1356498
TI  - Neurotransmission in human resistance arteries: contribution of alpha 1- and
      alpha 2-adrenoceptors but not P 2-purinoceptors.
AB  - The contribution of postjunctional alpha 1- and alpha 2-adrenoceptors and P2
      purinoceptors to the neuroeffector response was examined in isolated segments of
      human subcutaneous resistance arteries. Electrical field stimulation (EFS, 20 V,
      0.2 ms, 1-25 Hz) elicited a maximum contractile response which was 38.2 +/- 1.6%
      of that elicited by exogenously applied (5 microM) noradrenaline (n = 56).
      Tetrodotoxin (1 microM), used to inhibit neurotransmission, reduced the
      electrically evoked response to 24.7 +/- 4.4% (n = 10) of the control response.
      The alpha 1-adrenoceptor antagonist prazosin (1 microM) reduced the maximum EFS
      contractile response to 64.8 +/- 5.5% of the control response (n = 17).
      Application of the alpha 2-adrenoceptor antagonist yohimbine (0.1 microM) reduced
      the maximum EFS response to 68.2 +/- 8.2% of the control response (n = 9). In the
      presence of prazosin plus yohimbine at the above-mentioned concentrations the
      maximum response to EFS was reduced to 47.6 +/- 6.7% (n = 11). Responses
      following alpha-blockade were not statistically different from those in the
      presence of tetrodotoxin, but the mean responses indicate that a non-adrenergic
      component to the EFS response cannot be discounted. Desensitisation of P 2
      purinoceptors with alpha, beta-methylene ATP had no effect on responses to EFS;
      therefore under the conditions studied these receptors do not appear to be
      involved in neurotransmission. These results confirm the presence of
      postjunctional alpha 1- and alpha 2-adrenoceptors in human resistance arteries
      and for the first time demonstrate that the postjunctional alpha 2-adrenoceptor
      is important in modulating vascular responses elicited by intramural sympathetic
      nerve fibres.

PMID- 1356499
TI  - [Diffuse pulmonary hemorrhage due to capillaritis in a patient with typical
      periarteritis nodosa and necrotizing glomerulonephritis. Relationship with
      overlapping vasculitic syndrome and Wegener's granulomatosis].
AB  - Clinical and pathological postmortem study of a patient with NPA which died due
      to a fulminant pulmonary hemorrhage. In the postmortem study, diffuse pulmonary
      capillaries was observed as the cause of the disease, as well as lesions of
      necrotizing glomerulonephritis with granulomas, within the framework of a typical
      NPA. Correlation with the NPA-type overlapping polyangiitic syndrome and
      microscopic polyarteritis are discussed, as well as the correlation between the
      latter and Wegener's granulomatosis.

PMID- 1356500
TI  - Anxiolytic-like actions of anpirtoline in a mouse light-dark aversion paradigm.
AB  - The anxiolytic-like potential of anpirtoline was assessed in a mouse light/dark
      aversion test. Anpirtoline (1.0 ng kg(-1)-1.0 micrograms kg-1 i.p.) reduced the
      aversive responding of mice. This was detected as an increase in the latency to
      locate the non-aversive compartment and by decreases in the percentage of the
      time spent in the dark compartment, and the numbers of rears and line crossings
      in the dark compartment. In radioligand binding studies anpirtoline displayed
      submicromolar affinity for 5-HT1A, 5-HT1B and 5-HT3 receptor recognition sites
      (Ki = 151, 28 and 30 nM, respectively) and more modest affinity for 5-HT2
      receptor recognition sites (Ki = 1.48 microM). It is concluded that anpirtoline
      has a unique spectrum of affinity for 5-HT receptor subtypes, its interaction
      with which may account for its anxiolytic-like activity.

PMID- 1356503
TI  - The 8th International Congress of Biorheology. Yokohama, Japan, 3-8 August 1992.
      Abstracts.

PMID- 1356501
TI  - Forcing expression of a soybean root glutamine synthetase gene in tobacco leaves
      induces a native gene encoding cytosolic enzyme.
AB  - Glutamine synthetase (GS; EC 6.3.1.2) is present in different subcellular
      compartments in plants. It is located in the cytoplasm in root and root nodules
      while generally present in the chloroplasts in leaves. The expression of GS
      gene(s) is enhanced in root nodules and in soybean roots treated with ammonia. We
      have isolated four genes encoding subunits of cytosolic GS from soybean (Glycine
      max L. cv. Prize). Promoter analysis of one of these genes (GS15) showed that it
      is expressed in a root-specific manner in transgenic tobacco and Lotus
      corniculatus, but is induced by ammonia only in the legume background. Making the
      GS15 gene expression constitutive by fusion with the CaMV-35S promoter led to the
      expression of GS in the leaves of transgenic tobacco plants. The soybean GS was
      functional and was located in the cytoplasm in tobacco leaves where this enzyme
      is not normally present. Forcing this change in the location of GS caused
      concomitant induction of the mRNA for a native cytosolic GS in the leaves of
      transgenic tobacco. Shifting the subcellular location of GS in transgenic plants
      apparently altered the nitrogen metabolism and forced the induction in leaves of
      a native GS gene encoding a cytosolic enzyme. The latter is normally expressed
      only in the root tissue of tobacco. This phenomenon may suggest a hitherto
      uncharacterized metabolic control on the expression of certain genes in plants.

PMID- 1356502
TI  - Antigen presentation by B lymphocytes to CD4+ T lymphocytes in vivo: importance
      for B lymphocyte and T lymphocyte activation.
AB  - B lymphocytes, like macrophages and dendritic cells, can present antigen to CD4+
      T cells. Antigen presentation by B cells is essential for the generation of an in
      vivo T cell dependent antibody response, and repeated antigen presentation by B
      cells to T cells is necessary to induce B cell clonal expansion. Presentation of
      antigen by resting B cells to unprimed T cells tolerizes T cells, while anti-IgD
      antibody activates B cells and allows B cell antigen presentation that
      productively activates T cells. However, activation is not all that is required
      for B cells to productively present antigen to T cells.

PMID- 1356504
TI  - [Biokinetics of a new prodrug gidazepam and its metabolite].
AB  - Pharmacodynamics and pharmacokinetics of a novel tranquilizing agent--gidazepam
      (I), a prodrug, and its physiologically active metabolite--7-bromo-5-phenyl-1,2
      di-hydro-3H-1,4- benzodiazepine-2-one (II) in mice organism were studied. The
      form of relationship was determined between the dynamics of the anticonvulsant
      effect of labelled (2-14C-) I and II and the kinetics of the content of 14C
      compounds in the experimental animals brain. It was noted that the biophase of
      the effect and the effector fragment of the scheme of biokinetics for I and II
      are identical. The effector prognosis of pharmacokinetics of I was realized. The
      comparison of the main characteristics of biokinetics for the prodrug (I) and
      drug (II) allowed us to reveal the nature of the quantitative differences of
      these pharmacological effects.

PMID- 1356505
TI  - [Characterization of cloned alpha-satellite sequence from the extrachromosomal
      DNA of HeLa cell culture].
AB  - We have obtained the alphoid DNA clones, pK1 and pK2, from the extrachromosomal
      DNA of Hela cells treated by cycloheximide (30 micrograms/ml). Nucleotide
      sequences of the clones were aligned. The sides of the pK1 and pK2 are 390 and
      184 bp, respectively. The marked RELP for the clones was not observed. The
      results of in situ hybridization have shown an approximately equal distribution
      of Ag-grains over major part of human chromosomes, with a slight preference for
      chromosomes 1, 5 and 19 (the 1-st group of alpha-satellite DNA). Therefore, the
      obtained alphoid sequences seem to be rather conservative and non-chromosome
      specific. We suppose that increase of the alphoid DNA content in the fraction of
      the extrachromosomal DNA under the cycloheximide treatment is a result of the
      sporadic statistical processes rather then consequence of the specific excision.

PMID- 1356506
TI  - [Tyrosine hydroxylase activity and expression of its gene in mice with
      contrasting capacity to dominate in social stress].
AB  - Changes of tyrosine hydroxylase (TH) activity and level of mRNA of TH gene in PT
      and CBA/Lac mouse strains, which are contrast by ability to dominate in
      heterogenous populations, were investigated. It was established, that the
      activity of TH both in dominate PT and subordinate CBA/Lac mice in hypothalamus,
      hippocampus and brain stem elevated in one hour after forming of
      micropopulations. But the appearance of this increase was different: activation
      of TH in hypothalamus and brain stem of PT mice was stronger then one in CBA/Lac
      mice. Moreover, the beginning of the reaction in brain stem of PT mice was
      earlier then that of CBA/Lac mice. MRNA level of TH gene in hypothalamus and
      brain stem in one hour was elevated only in PT mice for 50% and 200%,
      respectively. No changing in expression TH gene was found in hippocampus. In
      conclusion, it was suggested that the activation of catecholamine biosynthesis
      under social stress in hypothalamus and brain stem of male mice was due to the TH
      activation and increase of its gene expression.

PMID- 1356508
TI  - [Secretory activity of lactotrophs and its regulation by hypothalamic hormones in
      primary cultures of pituitary cells of rats of different ages].
AB  - Basal prolactin (PRL) secretion and the responses of lactotrophs to thyroliberin,
      dopamine and somatostatin were studied in the experiments employing primary
      monolayer cultures of pituitary cells obtained from developing rats of different
      ages. High responsiveness of PRL-secreting cells to the action of hypothalamic
      hormones was observed in the group of neonatal rats, although basal PRL release
      was about two orders lower in pituitary cultures of neonatal rats as compared to
      the cultures of immature, pubertal and adult animals. The investigation performed
      could reveal quantitative, but not qualitative differences in the reactions of
      lactotrophs of various age groups. It is concluded that postnatal development in
      the rat is coupled with significant changes of basal PRL release and to a lesser
      extent, with changes of lactotroph responsiveness to hypothalamic hormones.

PMID- 1356507
TI  - [Effects of amiridin and tacrine, drugs effective in Alzheimer's disease, on
      synaptosomal uptake of neuromediators].
AB  - The study of the drugs effective in the treatment of cognitive deficits and
      memory loss associated with senile dementia of the Alzheimer's type--tacrine and
      amiridin, acetylcholinesterase inhibitor physostigmine and nootrop piracetam on
      uptake of 3H-serotonin (3H-5-HT), 3H-adrenaline (3H-AD), 3H-noradrenaline (3H
      HA), 2H-dopamine (3H-DA), 3H-gamma-aminobutyric acid (3H-GABA), 3H-glutamic acid
      (3H-GLU), 3H-aspartic acid (3H-ASP) and 3H-glycine (3H-GLI) showed that tacrine
      and amiridin (5 x 10(-5) M) statistically significantly (P less than 0.05)
      inhibited the uptake of 3H-DA and 3H-5-HT. Physostigmine at concentration 5 x 10(
      4) M statistically significantly (P less than 0.05) inhibited uptake of 3H-5-HT
      only. Piracetam at concentration range 1-5 x 10(-3) M had no effect on uptake of
      all investigated neurotransmitters. The above finding suggest that the uptake of
      neurotransmitter in nerve terminals is not the main target of amiridin and
      tacrine.

PMID- 1356509
TI  - [Regulation of hormone secretion in primary cell cultures of human
      somatotropinomas].
AB  - The effects of somatostatin and thyroliberin (thyrotropin-releasing hormone; TRH)
      on growth hormone (GH) and prolactin (PRL) secretion were studied in short-term
      (0.5-3h) or long-term (21-24h) incubations using monolayer cell cultures of
      somatotropin obtained from surgical material of patients with acromegaly. High
      sensitivity of both GH and PRL release to inhibitory action of somatostatin (10(
      11) M) was established. We could not reveal the unambiguous influence of TRH on
      somatotropic function in the in vivo and in vitro conditions, as compared to the
      action of this tripeptide on PRL secretion. The results obtained permit us to
      propose that cell cultures of pituitary adenomata represent adequate and
      convenient models for studying the pathogenesis of tumor processes in the
      pituitary gland and for the development of new procedures of pharmacotherapy.

PMID- 1356510
TI  - Clonal involvement of granulocytes and monocytes, but not of T and B lymphocytes
      and natural killer cells in patients with myelodysplasia: analysis by X-linked
      restriction fragment length polymorphisms and polymerase chain reaction of the
      phosphoglycerate kinase gene.
AB  - To determine the clonal nature of hematopoiesis and to assess lineage involvement
      in patients with myelodysplastic syndromes (MDS), we used restriction fragment
      length polymorphisms of the X-linked genes phosphoglycerate kinase (PGK1) and
      hypoxanthine phosphoribosyltransferase (HPRT) and the X-linked probe M27 beta.
      Eleven female MDS patients heterozygous for at least one of these probes were
      studied: 3 with refractory anemia (RA), 2 with RA with ringed sideroblasts
      (RARS), 2 with chronic myelomonocytic leukemia (CMML), and 4 with RA with excess
      of blasts in transformation (RAEB-t). All exhibited clonal hematopoiesis as
      determined by Southern analysis of DNA prepared from peripheral blood (PB) and/or
      bone marrow (BM) cells. In three of the six patients heterozygous for the PGK1
      gene, purified cell suspensions of polymorphonuclear cells (PMN), monocytes,
      lymphocytes, and/or T cells prepared from PB were tested. In addition, five of
      these patients were analyzed by a polymerase chain reaction (PCR)-based procedure
      as described recently. This method was slightly adapted to facilitate the
      analysis of cell lysates of fluorescence-activated cell sorted (FACS) monocytes,
      T and B lymphocytes, and natural killer (NK) cells. The outcome of Southern and
      PCR analysis was concordant, showing that PMN and monocytes were clonally
      derived, whereas circulating T and B lymphocytes and NK cells exhibited random X
      chromosome inactivation compatible with a polyclonal pattern. To address the
      question of whether T cells are derived from unaffected progenitor cells or that
      their origin had antedated the onset of MDS, naive and memory T cells were
      analyzed separately. Both subsets showed a polyclonal pattern. However, in one
      patient analysis of constitutive DNA suggested a skewed methylation, and the
      presence of clonal lymphocytes against a background of polyclonal lymphoid cells
      cannot be ruled out in this patient. PCR analysis of PB and BM cells showed a
      nonrandom, unilateral pattern of X-inactivation, compatible with a mixture of
      clonally (myeloid) and polyclonally (lymphoid) derived cells. In conclusion, in
      some patients, MDS represents a disorder with clonal hematopoiesis restricted to
      cells of myeloid origin, whereas a random X-inactivation pattern is found in
      lymphoid cells.

PMID- 1356512
TI  - Polymerase chain reaction analysis of an NcoI polymorphism of the human
      erythrocyte ankyrin gene.

PMID- 1356511
TI  - Deletions involving two distinct regions of 6q in B-cell non-Hodgkin lymphoma.
AB  - The recurrent loss of genetic material from a specific chromosomal region in a
      given tumor type suggests the presence of a tumor-suppressor gene, the loss or
      inactivation of which may be relevant for tumorigenesis. In this study, we
      provide molecular evidence for the recurrent association between deletions on the
      long arm of chromosome 6 and B-cell non-Hodgkin lymphoma (B-NHL). Normal and
      tumor DNAs from 71 cases of B-NHL were studied for loss of constitutional
      heterozygosity (LOH) at 19 loci on chromosome 6 using a panel of restriction
      fragment length polymorphism (RFLP) probes. LOH, indicating deletion of all or
      part of 6q, was detected in 16 of 71 cases (22.5%), ranging from low-grade to
      high-grade B-NHL. The isolated loss of 6p or the loss of other chromosomes (8,
      17, 22) tested as controls for specificity was not observed in any case.
      Comparison of the extent of the deletions among different cases allowed the
      identification of two distinct regions of minimal deletion (RMD) at 6q25 to 6q27
      (RMD-1) and at 6q21 to 6q23 (RMD-2), respectively, suggesting the existence of
      two tumor-suppressor genes. These data support a role for 6q deletions in B-NHL
      pathogenesis and provide a basis for identifying the corresponding tumor
      suppressor genes.

PMID- 1356513
TI  - Phenotypic analysis of mouse hematopoietic stem cells shows a Thy-1-negative
      subset.
AB  - Mouse hematopoietic stem cells can be identified and enriched from populations of
      normal bone marrow cells by immunofluorescent labeling of cell surface molecules
      followed by flow cytometric separation. We show here that the majority of
      hematopoietic stem cell activity, as defined by long-term competitive
      repopulation of irradiated animals and by a secondary transplant assay for spleen
      colony-forming units (CFU-S), could be localized in Ly-6b haplotype mice to a
      fraction of bone marrow cells that expresses the Ly-6A/E (Sca-1) molecule.
      Further, an analysis of hematopoietic stem cell activity in bone marrow of mouse
      strains expressing the Thy-1.1 allele indicated that the vast majority of
      activity was included in the Thy-1low population. In contrast, hematopoietic stem
      cell activity found in the bone marrow of Thy-1.2 genotype mouse strains was
      recovered in both the Thy-1neg and the Thy-1low populations. However, similar to
      Thy-1.1 strains, most activity was localized to the Ly-6A/E+ population of cells.
      The difference in Thy-1 phenotype of hematopoietic stem cell activity apparent
      between Thy-1.1- and Thy-1.2-expressing mouse strains was not caused by
      differences in the staining intensity of monoclonal antibodies (MoAbs) specific
      for the Thy-1 alleles. Furthermore, an antiframework MoAb that stains both
      alleles of Thy-1 separated hematopoietic stem cell activity from mice expressing
      the two alleles in the same manner as did allele-specific MoAb. The results of
      this study show that Thy-1 expression is not an invariant characteristic of mouse
      hematopoietic stem cells, and that mice expressing the Thy-1.1 allele are unique
      in that hematopoietic stem cell activity is found exclusively in the Thy-1low
      population.

PMID- 1356514
TI  - Glutathione depletion in chronic lymphocytic leukemia B lymphocytes.
AB  - Glutathione (GSH) content may be the major determinant of a cell's sensitivity to
      cytotoxic alkylating agents. In the present study, the GSH concentration was
      determined in lymphocytes isolated from the blood of normal subjects and patients
      with chronic lymphocytic leukemia (CLL). Comparable levels were found in both
      types of cells. Incubation for 20 hours led to a decrease in GSH to 51% of
      baseline values in CLL B cells. Under the same conditions, normal B- or T
      lymphocyte GSH content remained constant. GSH depletion was shown to be a
      characteristic of the B-CLL B lymphocyte. It was not found in the T cells of
      patients with B-CLL or in cells from patients with T-CLL. Chlorambucil (CLB)
      contributes to the decrease in GSH in B-CLL lymphocytes; after incubation with
      the drug, lower levels of GSH were found than in the normal B or T lymphocytes, B
      CLL T cells, or T-CLL (CD4 or CD8) cells. GSH depletion of CLL B lymphocytes may
      be related to the greater therapeutic efficacy of CLB in B-CLL than in T-CLL.

PMID- 1356515
TI  - Progressive disease after high-dose therapy and autologous transplantation for
      lymphoid malignancy: clinical course and patient follow-up.
AB  - Of 364 patients with lymphoid malignancy who underwent high-dose therapy with
      autologous bone marrow transplantation (ABMT) or peripheral stem cell
      transplantation (PSCT), 169 patients have had progressive disease after the
      procedure. The median survival from the time of relapse for patients with
      Hodgkin's disease (HD) who progressed after the transplant was 10.5 months. This
      compares with a median survival of 3 months for relapsed non-Hodgkin's lymphoma
      (NHL) patients (P = .0036). After failing transplantation, 56 patients were
      treated with further chemotherapy, 35 with involved field irradiation therapy,
      and 18 patients were treated with combination chemotherapy and irradiation. Seven
      patients received biologic therapy and seven patients underwent a second bone
      marrow transplant. The remainder of the patients were believed to be too ill for
      further therapy or chose not to receive further treatment for their recurrent
      lymphoid malignancy. Sixty of the 169 patients with progressive disease after the
      transplant are still alive; however, only 18 patients are alive off therapy
      without evidence of active disease after their relapse. Ten of the 18 patients
      are still less than 12 months past their posttransplant salvage therapy and are
      at high-risk for relapse. Five patients are progression free at 15 to 36 months
      after their posttransplant relapse. Only three patients (two NHL and one HD)
      treated with other modalities after autologous transplant failure are alive
      without evidence of disease and have been observed at least 4 years postrelapse.
      Although a few patients will have a durable response to subsequent therapy, the
      majority of patients who have progressive disease after an autologous transplant
      for lymphoid malignancy will succumb to recurrent disease within a short period
      of time.

PMID- 1356516
TI  - Overview of new treatments for breast cancer.
AB  - Progress in the treatment of breast cancer developed along multiple directions of
      research during the last decade. The concept of dose-intensity was addressed
      through retrospective analyses and prospective randomized trials. It was
      confirmed that dose-intensity correlates with higher response rates, but the
      effect of dose-intensive treatments on survival still needs to be established.
      Several new cytotoxic drugs have appeared during the last several years. Taxol,
      navelbine, and anthrapyrazole CI-941 have been found to have major efficacy
      against breast cancer, with response rates exceeding 50%. Amonafide, lonidamine,
      and elliptinium analogs were also shown to be effective, although to a lesser
      degree. Antiestrogen analogs, new aromatase inhibitors, and LHRH analogs are
      recent developments that are changing the face of hormonal therapy. Monoclonal
      antibodies are being developed and evaluated for tumor imaging applications and
      as vehicles for specific antitumor agents (cytotoxics, radioisotopes, and
      toxins). Expanding knowledge about the basic biology of breast cancer has led to
      the identification of growth factors and their receptors, which may be exploited
      for therapeutic purposes in the not too distant future.

PMID- 1356517
TI  - Comparison of PCNA/cyclin immunohistochemistry with flow cytometric S-phase
      fraction in breast cancer.
AB  - Kinetic index determined by enumeration of neoplastic cells positive for
      proliferative cell nuclear antigen (PCNA) in 70 breast carcinomas (avidin-biotin
      immunoperoxidase technique) was compared to synthesis-phase fraction (S-phase, or
      SPF) values obtained by flow cytometry (FCM) using a multiparametric, 2 color
      method (dual-label propidium iodide/cytokeratin-FITC). The percent PCNA positive
      tumor cells (12.5% mean, range 1-28%) was significantly greater in aneuploid
      tumors (14.2% mean, N = 35) compared to diploid range tumors (10.7% mean, N = 35)
      (p less than 0.05), and was correlated with SPF derived from ungated DNA
      histograms (12.5% mean +/- 5.5%, r = 0.45, p less than 0.001). Marginally
      stronger statistical correlations were observed between the PCNA index and SPF
      values calculated from cytokeratin-gated (15.8% mean, r = 0.53, p less than
      0.001) DNA histograms or from SPF values obtained following linear baseline
      debris subtraction (mean = 8.1%, r = 0.48, p less than 0.001). Significant
      associations were identified between PCNA index and prognostically important
      clinicopathologic parameters including nuclear grade (p = 0.014), presence of
      necrosis (p = 0.005), and angiolymphatic invasion (p = 0.003). We conclude: 1)
      PCNA index is comparable to FCM SPF and correlates with factors of known
      prognostic importance in carcinoma of the breast; 2) baseline debris and
      contaminating events derived from non-epithelial cells both represent significant
      artifacts in proliferative fraction estimates derived from FCM DNA histograms;
      and 3) multiparametric analysis may represent one means of improving the
      specificity and clinical value of FCM SPF determinations.

PMID- 1356518
TI  - International Conference on Growth Control in Breast Cancer: Basic and Clinical
      Aspects. Taormina, Italy, December 13-14, 1991. Abstracts.

PMID- 1356519
TI  - Gastric acid inhibitory profile of ebrotidine, a novel H2-receptor antagonist in
      humans.
AB  - This study was designed to assess the gastric secretory effects of ebrotidine, a
      novel H2 receptor antagonist, in humans. Three groups (A, B and C) of male
      subjects with normal gastric mucosa were used. Group A (6 subjects) was used to
      determine the dose-dependency of gastric inhibitory effect of ebrotidine on basal
      and pentagastrin-induced maximal acid output. Group B (8 subjects) was employed
      to examine the duration of the inhibitory effect of ebrotidine on basal and
      pentagastrin-induced acid secretion. In group C (6 subjects), the 24h pH-metry
      was assessed using intraluminal pH-electrode placed in the gastric corpus and
      connected to a portable recording unit. Single oral dose of ebrotidine (200, 400
      or 800 mg) caused a dose-dependent reduction in basal and pentagastrin-induced
      acid secretion that at a dose of 800 mg amounted to about 89% and 93%,
      respectively. This inhibition was still observed after 6h and averaged 72% and
      50%, respectively. After 12 and 24h upon the drug intake, both basal and
      pentagastrin-induced acid secretion returned to the control values. Single oral
      dose of ebrotidine (800 mg) caused a significant reduction in circadian acidity
      and resulted in a marked and significant reduction of intragastric acidity for
      about 6h upon the administration. This inhibition was accompanied by a transient
      increase in basal and postprandial gastrin levels. We conclude that ebrotidine is
      highly effective inhibitor of basal, pentagastrin-induced and circadian gastric
      acid secretion in humans.

PMID- 1356520
TI  - Ethical difficulties with randomized clinical trials involving cancer patients:
      examples from the field of gynecologic oncology.

PMID- 1356521
TI  - Computer-assisted video measurement of inhibition of ciliary beat frequency of
      human nasal epithelium in vitro by xylometazoline.
AB  - The effect of xylometazoline, an alpha-adrenergic agonist, on ciliary beat
      frequency (CBF) was tested on samples of human nasal epithelium in vitro.
      Ciliated tissue was obtained from the inferior nasal turbinates of five normal
      individuals. CBF was measured from video recordings of ciliary activity using a
      computer-assisted photometric technique. The mean CBF of cells from the five
      subjects, followed for 40 min without xylometazoline, was 12.0 +/- 1.1 Hz. All
      concentrations of xylometazoline significantly decreased ciliary beat frequency.
      After a 10-min exposure, the mean CBF dropped to 3.8 +/- 0.4 with 0.1%
      xylometazoline, 4.9 +/- 1.0 with 0.05%, and 8.1 +/- 0.9 with 0.025%. Washing with
      control culture medium at least partially reversed the inhibition within 10 min.
      Phentolamine (10(-3) M), an alpha-adrenergic antagonist, did not alter CBF
      significantly when used alone, but partially blocked the strong cilioinhibitory
      effect of xylometazoline. This action of xylometazoline is similar to that of
      several commercially prepared decongestants that contain potentially ciliotoxic
      preservatives in addition to alpha-adrenergic agonists and supports the view that
      alpha-adrenergic agonists act directly on ciliated cells to inhibit ciliary
      activity.

PMID- 1356523
TI  - Otoneurology.
AB  - This review on progress in otoneurology focuses on peripheral and central
      vestibular disorders rather than auditory dysfunction. Recent literature reflects
      an imbalance between quantity and quality. For instance, several of the numerous
      papers on Meniere's disease contribute little to furthering our knowledge of
      pathophysiology and treatment. The comparatively few papers on neurotransmitters,
      otolith function, and central vestibular pathway syndromes illustrate a promising
      area for scientific and clinical research in the future. Identification of
      vestibular pathway lesions as the cause of many oculomotor syndromes, such as
      downbeat and upbeat nystagmus or ocular tilt reaction lesions, will broaden the
      scope of otoneurology and the clinical responsibility of the neurologist.

PMID- 1356524
TI  - Multiple endocrine neoplasia type 2A.
AB  - A 40-year-old woman was admitted with complaints of headache, palpitation and
      diaphoresis. She had undergone right hemithyroidectomy 12 years previously.
      Histological reexamination of the operative specimen revealed a medullary thyroid
      carcinoma. Abdominal ultrasonography, CT scan and angiography showed bilateral
      adrenal tumors. Serum catecholamine levels in both adrenal veins were high. Based
      on these data, bilateral adrenalectomy was performed. Histological examination
      confirmed the diagnosis of pheochromocytomas. After operation, serum calcitonin
      and urinary noradrenaline levels were still high. Further examination by 131I
      metaiodobenzylguanidine (MIBG) scintigraphy is planned.

PMID- 1356522
TI  - Synthesis and trafficking of prion proteins in cultured cells.
AB  - Scrapie prions are composed largely, if not entirely, of the scrapie prion
      protein (PrPSc) that is encoded by a chromosomal gene. Scrapie-infected mouse
      neuroblastoma (ScN2a) and hamster brain (ScHaB) cells synthesize PrPSc from the
      normal PrP isoform (PrPC) or a precursor through a posttranslational process. In
      pulse-chase radiolabeling experiments, we found that presence of brefeldin A
      (BFA) during both the pulse and the chase periods prevented the synthesis of
      PrPSc. Removal of BFA after the chase permitted synthesis of PrPSc to resume. BFA
      also blocked the export of nascent PrPC to the cell surface but did not alter the
      distribution of intracellular deposits of PrPSc. Under the same conditions, BFA
      caused the redistribution of the Golgi marker MG160 into the endoplasmic
      reticulum (ER). Using monensin as an inhibitor of mid-Golgi glycosylation, we
      determined that PrP traverses the mid-Golgi stack before acquiring protease
      resistance. About 1 h after the formation of PrPSc, its N-terminus was removed by
      a proteolytic process that was inhibited by ammonium chloride, chloroquine, and
      monensin, arguing that this is a lysosomal event. These results suggest that the
      ER is not competent for the synthesis of PrPSc and that the synthesis of PrPSc
      occurs during the transit of PrP between the mid-Golgi stack and lysosomes.
      Presumably, the endocytic pathway features in the synthesis of PrPSc.

PMID- 1356525
TI  - The proliferative kinetics of somatostatin-producing cells in the rat antral
      mucosa after truncal vagotomy.
AB  - The kinetics of somatostatin-producing cells (D-cells) in the rat antral mucosa
      after truncal vagotomy were studied using double immunostaining for
      bromodeoxyuridine (BrdU) and somatostatin. Both the concentration of somatostatin
      and D-cell density in the antral mucosa demonstrated a significant increase on
      the 3rd day after truncal vagotomy. With the single labeling of BrdU, a few D
      cells showed positive immunostaining for BrdU throughout the experimental period
      in both vagotomized and sham operated rats. With cumulative labeling, the BrdU
      labeled cells demonstrated a linear increase in an identical number for each
      experimental time-point in both groups. The labeling index of BrdU in the D-cells
      increased significantly, beginning on the 3rd day and attaining a maximum level
      of 41.8% on the 10th day, in the vagotomized group after cumulative labeling. In
      this group, however, the density of D-cells with no immunoreactive BrdU also
      increased quickly on the 3rd day with cumulative labeling. The present study
      indicates that the most important factor involving D-cell hyperplasia observed
      after truncal vagotomy is the activation of pre-existing D-cells to synthesize
      and release hormones, together with the rapid replication of progenitor cells and
      their maturation to D-cells.

PMID- 1356526
TI  - A case of duodenal carcinoma presenting as a submucosal tumor.
AB  - This paper describes a patient with duodenal carcinoma showing the features of a
      submucosal tumor, leading to difficulty in making an accurate preoperative
      diagnosis. A 63-year-old woman was admitted for investigation of a duodenal mass.
      An examination of the upper gastrointestinal tract revealed a semicircular
      compression of the stomach and the duodenum. Endoscopy of the stomach and
      duodenum disclosed a hemispherical tumor with a deep ulcer in the apex. Computer
      tomography revealed a tumor of about 5 cm in diameter at the same site.
      Laparotomy was performed under the tentative diagnosis of a submucosal tumor. A
      tumor was found occupying the duodenum, which compressed the gastric antrum
      exteriorly, and was also adherent to the head of the pancreas by direct invasion.
      A curative resection was performed by combining a pancreatoduodenectomy with a
      transverse colectomy along with regional lymph node clearance. A microscopic
      examination showed that the tumor contained neoplastic cells growing in a tubular
      pattern, particularly in its peripheral regions. Thus, this lesion was finally
      diagnosed as primary adenocarcinoma of the duodenum.

PMID- 1356527
TI  - Hormonal treatment of cryptorchidism--hCG or GnRH--a multicentre study.
AB  - In a modified, double-blind controlled study, 163 prepubertal boys (aged 1.8-13.0
      years) with bilateral and 94 (aged 1.5-13.1 years) with unilateral cryptorchidism
      were allocated to treatment with either human chorionic gonadotrophin (im),
      gonadotrophin releasing hormone (intranasally) or placebo (intranasally). In
      individuals with the bilateral condition treatment with human chorionic
      gonadotrophin resulted in complete descent of both testes in 23% of patients.
      Treatment with human chorionic gonadotrophin in unilateral cryptorchidism
      resulted in complete descent in 19% of patients; all results were significantly
      better than those obtained with gonadotrophin releasing hormone or placebo.
      Linear and logistic regression analysis of the results obtained by treatment of
      bilateral disease showed that all treatments were more successful the younger the
      age of the boys. The data indicated that bilateral and unilateral cryptorchidism
      respond differently to hormonal treatment. We suggest that human chorionic
      gonadotrophin should be the first choice of treatment for prepubertal boys older
      than one year.

PMID- 1356528
TI  - 8th International Natural Killer Cell Workshop and 1st Meeting of the Society for
      Natural Immunity. Molecular and cellular aspects of natural killer cell
      triggering and signalling. October 4-6, 1992, St. Petersburg Beach, Florida.
      Abstracts.

PMID- 1356529
TI  - Prevention of Pneumocystis carinii pneumonia and toxoplasmic encephalitis in
      human immunodeficiency virus infected patients: a clinical approach comparing
      aerosolized pentamidine and pyrimethamine/sulfadoxine.
AB  - The incidence of Pneumocystis carinii pneumonia (PCP) and toxoplasmic
      encephalitis (TE) was analyzed in 83 human immunodeficiency virus (HIV)-infected
      patients who inhaled aerosolized pentamidine (AP) either for primary prophylaxis
      (group Ia) or secondary prophylaxis (group IIa) of PCP. These cohorts were
      compared with two historical groups of patients who took Fansidar
      (pyrimethamine/sulfadoxine) for primary prophylaxis (group Ib) or secondary
      prophylaxis (group IIb) of PCP. The follow-up was 3-41 months (median 8 months).
      PCP did not occur in group Ia but was seen in 1 patient of group Ib (5%). TE was
      observed in 3 patients of group Ia (7.3%) and in 1 patient of group Ib (5%). PCP
      relapses were seen in 5 patients of group IIa (11.9%) and in 3 patients of group
      IIb (6.9%), whereas TE occurred in 13 patients of group IIa (30.9%) and in 1
      patient of group IIb (2.3%). 20.3% of patients with CD4+ counts less than or
      equal to 100/microliters and only 7.7% of those with CD4+ counts greater than
      100/microliters developed toxoplasmosis. In conclusion, Fansidar rather than AP
      prophylaxis should be recommended for patients with a history of PCP or
      toxoplasmosis and for all HIV-infected patients with CD4+ counts less than or
      equal to 100/microliters. In patients with CD4+ lymphocyte counts between 100 and
      200/microliters, AP prophylaxis appears appropriate.

PMID- 1356530
TI  - Gallstones in acromegalic patients undergoing different treatment regimens.
AB  - The frequency of gallstones during long-term treatment with the somatostatin
      analogue octreotide reported in different studies varies from 0% to 50%, the
      reason for this variation being unknown. Therefore, we examined 58 acromegalic
      patients undergoing different treatment regimens for the frequency of gallstones.
      Thirteen were treated with octreotide, 20 with bromocriptine, and 25 had no
      medical treatment after successful neurosurgery. Also, 58 patients without known
      gallbladder disease served as controls. The postprandial gallbladder contraction
      was also investigated in 27 acromegalic patients (10 with octreotide, 10 with
      bromocriptine, and 7 with no medical therapy). Ten of the 58 acromegalic patients
      were found to have gallstones, 4 of 25 receiving no medical treatment, 4 of 20
      treated with dopamine agonists, and 2 of 13 treated with octreotide. In 9 of the
      58 control patients, gallstones were detected. Although in the octreotide group
      the gallstones were newly formed under therapy, there was no difference in
      gallstone prevalence between the different treatment regimens and the control
      group. However, the postprandial gallbladder contraction was significantly more
      often inhibited during octreotide therapy, and this effect was most pronounced
      during the first hours following injection. Differences in the timing of
      injections therefore may be an explanation of the variable incidence of
      cholelithiasis in the different studies.

PMID- 1356531
TI  - Development of ulcerative colitis under the immunosuppressive effect of
      cyclosporine.
AB  - In recent studies, cyclosporine has been used for the treatment of both
      ulcerative colitis and Crohn's disease. The results of these studies were
      variable. We report on a patient who was treated for 6 years with cyclosporine
      after kidney transplantation. He developed chronic distal colitis with all the
      features of ulcerative colitis. An infectious etiology of the colitis was
      carefully excluded. High-dose treatment with methylprednisolone was required to
      induce remission. This report shows that immunosuppressive therapy with
      cyclosporine did not prevent the development of ulcerative colitis in this
      patient.

PMID- 1356532
TI  - Modulation of the incidence of hamster pulmonary endocrine cell hyperplasia by
      unilateral collapse of the lung.
AB  - We evaluated the effects of the unilateral collapse of the left lung on the
      formation of pulmonary endocrine cell hyperplasia (PECH) induced by 4
      nitroquinoline 1-oxide (4NQO) in Syrian golden hamsters. Ten hamsters were
      injected subcutaneously with 20 mg/kg body weight of 4NQO, once a week for 4
      weeks and treated with injection of silicone rubber into the left thorax at the
      8th experimental week. Another 30 animals were divided into three groups: treated
      with 4NQO only, left lung collapse only, and vehicle only. All animals were
      sacrificed at the 30th week. The lung tissues were embedded in paraffin; 50
      serial sections were made from the tissues of each animal and were studied
      histologically and immunohistochemically. PECH showed a positive immunostain for
      calcitonin and/or serotonin. In the uncollapsed right lungs of the animals
      treated with both 4NQO and unilateral collapse, the mean incidence of PECH was
      12.2 x 10(-2)/mm3 lung volume; the incidences of PECH in the animals treated with
      4NQO only, collapse only, and vehicle only were 4.1, 3.8, and 1.4 x 10(-2)/mm3,
      respectively. In the collapsed left lungs, PECH did not form, regardless of 4NQO
      treatment. This study demonstrates that unilateral collapse of the lung modulates
      the incidence of PECH induced by 4NQO in hamsters.

PMID- 1356533
TI  - Abstracts of the Vth Congress of the European College of Neuropsychopharmacology.
      Marbella, Spain, 18-21 October 1992.

PMID- 1356534
TI  - The maize auxotrophic mutant orange pericarp is defective in duplicate genes for
      tryptophan synthase beta.
AB  - orange pericarp (orp) is a seedling lethal mutant of maize caused by mutations in
      the duplicate unlinked recessive loci orp1 and orp2. Mutant seedlings accumulate
      two tryptophan precursors, anthranilate and indole, suggesting a block in
      tryptophan biosynthesis. Results from feeding studies and enzyme assays indicate
      that the orp mutant is defective in tryptophan synthase beta activity. Thus, orp
      is one of only a few amino acid auxotrophic mutants to be characterized in
      plants. Two genes encoding tryptophan synthase beta were isolated from maize and
      sequenced. Both genes encode polypeptides with high homology to tryptophan
      synthase beta enzymes from other organisms. The cloned genes were mapped by
      restriction fragment length polymorphism analysis to approximately the same
      chromosomal locations as the genetically mapped factors orp1 and orp2. RNA
      analysis indicates that both genes are expressed in all tissues examined from
      normal plants. Together, the biochemical, genetic, and molecular data verify the
      identity of orp1 and orp2 as duplicate structural genes for the beta subunit of
      tryptophan synthase.

PMID- 1356535
TI  - Mutations at the Arabidopsis CHM locus promote rearrangements of the
      mitochondrial genome.
AB  - Nuclear recessive mutations at the chloroplast mutator (CHM) locus of Arabidopsis
      produce a variegated phenotype that is inherited in a non-Mendelian fashion.
      Molecular analysis of the cytoplasmic genomes of variegated plants from two
      independent chm mutant lines, using specific chloroplast and mitochondrial
      probes, showed that the chm mutations reproducibly induce the appearance of
      specific new restriction fragments in the mitochondrial genome. The presence of
      these restriction fragments cosegregated with the variegated phenotype in the
      progeny of crosses between mutant and wild-type plants. Sequence analysis of one
      of the new restriction fragments found in the variegated plants suggested that it
      was the product of a rearrangement event involving regions of the mitochondrial
      genome. Thus, it appears that the CHM locus may encode a protein involved in the
      control of specific mitochondrial DNA reorganization events.

PMID- 1356536
TI  - Pinning down loose ends: mapping telomeres and factors affecting their length.
AB  - A degenerately repeated sequence, proximal to the telomere heptanucleotide repeat
      in maize, contains restriction enzyme sites that permit the separation of
      telomeres from the rest of the chromosomes. Probing with a telomere-specific
      oligonucleotide revealed genotype-dependent telomere lengths that vary more than
      25-fold in maize among the 22 inbreds that have been surveyed. These lengths were
      found to segregate reproducibly in a recombinant inbred family where 50% of the
      variation can be accounted for by three loci. The dynamic control over telomere
      length in maize appears to act rapidly to achieve new genotypically determined
      telomere lengths in the F1. Clones of telomere proximal sequences were used to
      map restriction fragment length loci at the distal ends of eight of 20 chromosome
      arms.

PMID- 1356538
TI  - [Maternal pulmonary edema as an anesthesia complication after intravenous
      tocolysis and stimulating of lung maturation].
AB  - Maternal lung edema due to the use of beta-mimetic tocolytic agents is a well
      documented complication. The risk increases if several other factors are present:
      infectious diseases, the use of inhaled anesthetics, EPH gestosis, hydramnios,
      twin gestation and preexisting cardiovascular disease. The complications induced
      by beta-mimetic tocolytic agents can be reduced by remembering their side effects
      and contraindications and restricting fluid intake. During obstetric general
      anesthesia in patients undergoing tocolysis, the infusion of large amounts of
      saline, as is widely practised today, is strictly contraindicated.

PMID- 1356537
TI  - Differential expression of two MADS box genes in wild-type and mutant petunia
      flowers.
AB  - We isolated and characterized two flower-specific genes from petunia. The protein
      products of these genes, designated floral binding protein 1 (FBP1) and 2 (FBP2),
      are putative transcription factors with the MADS box DNA binding domain. RNA gel
      blot analysis showed that the fbp1 gene is exclusively expressed in petals and
      stamen of petunia flowers. In contrast, the FBP1 protein was only detectable in
      petals and not in stamens, suggesting post-transcriptional regulation of the fbp1
      gene in these tissues. The fbp2 gene is expressed in petals, stamen, carpels, and
      at a very low level in sepals but not in vegetative tissues. We analyzed the
      spatial expression of these fbp genes in floral organs of two homeotic flower
      mutants. In the blind mutant, whose flower limbs are transformed into antheroid
      structures on top of normal tubes, identical expression levels of both genes were
      observed in the antheroid structures as in normal anthers. In the homeotic mutant
      green petals, the petals are replaced by sepaloid organs in which the expression
      of fbp1 is strongly reduced but not completely abolished. Our results suggest a
      regulation of the fbp1 gene expression by the green petals (gp) gene. Expression
      of the fbp2 gene was not affected in the green petals mutant. In contrast to the
      proposed models describing floral morphogenesis, our data indicated that homeotic
      genes can be functional in one whorl only.

PMID- 1356539
TI  - [Contribution of molecular genetics to the understanding of chemoresistance of
      Plasmodium falciparum].
AB  - Resistance to pyrimethamine and proguanil is due to a single point mutation in
      the gene that codes for dihydrofolate reductase. A single mutation gives rise to
      resistance to only one of the drugs. Resistance to both drugs results from
      several mutations. Chloroquine resistance phenotype is due to a rapid efflux of
      the drug from the parasite's digestive vacuole. This efflux is associated with a
      transmembrane permeability glycoprotein, or P-gp, which is similar to the protein
      implicated in the multidrug resistant phenotype of some cancer cells. However,
      one or several other poorly understood major gene(s) may be involved. Drugs which
      can inhibit the supposed affinity of P-gp for chloroquine are under study.

PMID- 1356540
TI  - Drug-related methods for alleviation of stress in dentistry.
AB  - For many patients, dental procedures can cause a great deal of anxiety and fear.
      These emotions are part of a stress reaction, which, in physiologic terms, can
      pose a serious risk, particularly to patients with pre-existing cardiopulmonary
      disorders. In each case the dentist must decide whether anxiolytic stress
      reducing treatment is indicated, and which method should be used. Besides certain
      psychotherapeutic techniques, numerous drugs (neuroleptics, barbiturates, beta
      blockers, and benzodiazepines) are available for this purpose. This paper reviews
      these types of drugs and offers recommendations for their use.

PMID- 1356541
TI  - Postoperative pain control in children.

PMID- 1356542
TI  - Misuse of ecstasy.

PMID- 1356543
TI  - Misuse of ecstasy.

PMID- 1356544
TI  - Misuse of ecstasy.

PMID- 1356545
TI  - Misuse of ecstasy.

PMID- 1356546
TI  - Misuse of ecstasy.

PMID- 1356547
TI  - Preschool screening for cryptorchidism.

PMID- 1356548
TI  - Exercise, fitness and health.

PMID- 1356549
TI  - Preschool screening for cryptorchidism.

PMID- 1356550
TI  - Neuroleptic sensitivity in patients with senile dementia of Lewy body type.
AB  - OBJECTIVE: To determine the outcome of administration of neuroleptics to patients
      with senile dementia of Lewy body type confirmed at necropsy. DESIGN:
      Retrospective analysis of clinical notes blind to neuropathological diagnosis.
      SETTING: Specialist psychogeriatric assessment units referring cases for necropsy
      to a teaching hospital neuropathology service. PATIENTS: 41 elderly patients with
      diagnosis of either Alzheimer type dementia (n = 21) or Lewy body type dementia
      (n = 20) confirmed at necropsy. MAIN OUTCOME MEASURES: Clinical state including
      extrapyramidal features before and after neuroleptic treatment and survival
      analysis of patients showing severe neuroleptic sensitivity compared with the
      remainder in the group. RESULTS: 16 (80%) patients with Lewy body type dementia
      received neuroleptics, 13 (81%) of whom reacted adversely; in seven (54%) the
      reactions were severe. Survival analysis showed an increased mortality in the
      year after presentation to psychiatric services compared with patients with mild
      or no neuroleptic sensitivity (hazard ratio 2.70 (95% confidence interval 2.50
      8.99); (chi 2 = 2.68, p = 0.05). By contrast, only one (7%) of 14 patients with
      Alzheimer type dementia given neuroleptics showed severe neuroleptic sensitivity.
      CONCLUSIONS: Severe, and often fatal, neuroleptic sensitivity may occur in
      elderly patients with confusion, dementia, or behavioural disturbance. Its
      occurrence may indicate senile dementia of Lewy body type and this feature has
      been included in clinical diagnostic criteria for this type of dementia.

PMID- 1356552
TI  - Neural development. FESN Study Group.
AB  - The FESN-sponsored follow-up meeting on neural development highlighted progress
      toward understanding several central issues in developmental neurobiology with
      particular emphasis on investigation into the mechanisms of cell fate
      determination. In systems as diverse as the HSN neurons of C. elegans, the
      photoreceptor cells of the Drosophila eye, the wide range of cell types within
      the vertebrate retina and the neurons of the cerebral cortex, hindbrain and
      spinal cord, the importance of environment in the determination and maintenance
      of cell fate was clearly established. Advances in cell marking techniques,
      including fluorescent dye and retroviral tagging, have enabled the fates of cells
      in normal and heterotypic environments to be followed and have demonstrated the
      initial plasticity of the progenitor cell population in many systems. The recent
      establishment of in vitro systems for studying neural development should further
      define the precise nature and identity of the environmental signals that act to
      establish and maintain cell fate. Of course, establishment of cell identity is
      only the initial phase in the formation of the mature nervous system. Once the
      fate of individual cells is determined, migration of cells to appropriate
      locations, extension of axons to appropriate targets and refinement of neuronal
      circuitry must occur. Both the definition of genes that influence these processes
      in nematodes and recent advances in imaging techniques that provide a means of
      observing these later, dynamic processes in 'living' brain slices promise to
      significantly advance understanding of the complexities of development of
      functional nervous systems.

PMID- 1356551
TI  - Caffeine and the central nervous system: mechanisms of action, biochemical,
      metabolic and psychostimulant effects.
AB  - Caffeine is the most widely consumed central-nervous-system stimulant. Three main
      mechanisms of action of caffeine on the central nervous system have been
      described. Mobilization of intracellular calcium and inhibition of specific
      phosphodiesterases only occur at high non-physiological concentrations of
      caffeine. The only likely mechanism of action of the methylxanthine is the
      antagonism at the level of adenosine receptors. Caffeine increases energy
      metabolism throughout the brain but decreases at the same time cerebral blood
      flow, inducing a relative brain hypoperfusion. Caffeine activates noradrenaline
      neurons and seems to affect the local release of dopamine. Many of the alerting
      effects of caffeine may be related to the action of the methylxanthine on
      serotonin neurons. The methylxanthine induces dose-response increases in
      locomotor activity in animals. Its psychostimulant action on man is, however,
      often subtle and not very easy to detect. The effects of caffeine on learning,
      memory, performance and coordination are rather related to the methylxanthine
      action on arousal, vigilance and fatigue. Caffeine exerts obvious effects on
      anxiety and sleep which vary according to individual sensitivity to the
      methylxanthine. However, children in general do not appear more sensitive to
      methylxanthine effects than adults. The central nervous system does not seem to
      develop a great tolerance to the effects of caffeine although dependence and
      withdrawal symptoms are reported.

PMID- 1356553
TI  - Measles elimination in the Americas.

PMID- 1356554
TI  - Subdural empyema: a continuing threat.

PMID- 1356555
TI  - A68930 is a potent, full agonist at dopamine1 (D1) receptors in renal epithelial
      LLC-PK1 cells.
AB  - The selective dopamine1 (D1) receptor agonists SK&F 82526 (fenoldopam) and A68930
      and the mixed D1/D2 agonist SK&F 85174 were tested for their ability to stimulate
      adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in the porcine
      renal epithelial cell line, LLC-PK1. SK&F 82526 and SK&F 85174 were potent
      stimulators of cyclic AMP accumulation (EC50s 21.4 and 14.5 nM, respectively),
      but only partial agonists (intrinsic activities 31% and 46% of dopamine
      respectively). In contrast, A68930 was a potent, full agonist (EC50 12.7 nM,
      intrinsic activity 102% of dopamine). The stimulatory effects of A68930 and
      dopamine on cyclic AMP accumulation were not additive, and the stimulation of
      cyclic AMP accumulation by A68930 was blocked by the D1-selective antagonist, SCH
      23390. These properties of A68930 suggest that it may be a useful D1-selective
      agonist to study renal D1 receptor mechanisms in vitro and in vivo.

PMID- 1356556
TI  - Vasoconstriction of guinea-pig submucosal arterioles following sympathetic nerve
      stimulation is mediated by the release of ATP.
AB  - 1. The nature of the transmitter mediating vasoconstriction of guinea-pig
      submucosal arterioles following sympathetic nerve stimulation was studied. 2.
      Prazosin (0.1 microM) abolished the response to exogenously applied phenylephrine
      (1 microM) but had no effect on constrictions of submucosal arterioles evoked by
      nerve stimulation (100 pulses at 10 Hz). 3. Vasoconstrictions and excitatory
      junction potentials elicited by nerve stimulation were potentiated by idazoxan
      (0.1 microM). 4. Following reserpine treatment, catecholamine fluorescence was
      absent in submucosal arterioles but nerve-evoked vasoconstrictions were
      unaltered. 5. Vasoconstrictions and excitatory junction potentials recorded in
      response to sympathetic nerve stimulation, as well as constrictions evoked by
      exogenously applied ATP (3 microM), were abolished by the P2-purinoceptor
      antagonist, suramin (100 microM). Suramin had no effect on the vasoconstriction
      in response to noradrenaline (3 microM), or the nicotinic excitatory postsynaptic
      potentials (e.p.s.ps) and noradrenergic inhibitory postsynaptic potentials
      (i.p.s.ps) recorded from submucosal neurones. 6. We conclude that postjunctional
      responses of submucosal arterioles following sympathetic nerve stimulation are
      mediated solely through the activation of P2X-purinoceptors by ATP or a related
      purine nucleotide. The function of neurally released noradrenaline is to act
      through prejunctional alpha 2-adrenoceptors to depress transmitter release.

PMID- 1356557
TI  - The role of CD18 in IL-8 induced dermal and synovial inflammation.
AB  - 1. The intradermal administration of endothelial IL-8 (IL-8(1-77) or monocyte
      derived IL-8 (IL-8(1-72) to rabbits produced a concentration-dependent increase
      in plasma extravasation and an accumulation of polymorphonuclear leukocytes
      (PMNs) when measured over a 3 h time period. When plasma extravasation and PMN
      accumulation were measured over a 30 min time period no significant increases in
      PMN accumulation or plasma extravasation were observed in response to IL-8 alone.
      However, under these conditions, the addition of prostaglandin E2 (100 pmol)
      produced a significant potentiation of IL-8-induced plasma extravasation. There
      was no significant difference between the biological activities of IL-8(1-77) and
      IL-8(1-72). 2. Plasma extravasation and PMN accumulation induced by IL-8 were
      inhibited in rabbits pretreated with the monoclonal antibody designated IB4 (1 mg
      kg-1, i.v.) directed against the common beta chain (CD18) of the leukocyte
      integrins. 3. The intra-articular administration to rabbits of IL-8(1-77) (1
      nmol) resulted 24 h later in the appearance of a mixed population of leukocytes
      (PMNs and mononuclear cells) in synovial lavage fluid. Biochemical analyses
      revealed the presence of an increased level of sulphated proteoglycans (sPG) and
      of the metalloproteinase stromelysin. Pretreatment of rabbits with IB4 (3 mg kg
      1, i.v.) inhibited the accumulation of PMNs but had no effect on the mononuclear
      infiltrate nor on the levels of sPG or stromelysin. 4. The intradermal or intra
      articular injection of E. coli-derived endotoxin induced similar inflammatory
      changes to those observed with IL-8.The possibility that the biological
      activities of IL-8 were attributable to minor contamination with endotoxin is
      unlikely for two reasons. Firstly, biological effects of endotoxin were observed
      at levels greater than that contained in the IL-8 preparation. Secondly,reduction
      of the endotoxin content of the IL-8 preparation by a factor of 10 did not
      produce a concomitant reduction in the observed biological activity of the IL-8.

PMID- 1356558
TI  - The action of palytoxin on the isolated detrusor muscle of the rat.
AB  - 1. The effects of a coelenterate toxin, palytoxin (PTX) have been studied in the
      isolated detrusor muscle. of the rat. 2. PTX (1-100 nM) initiated concentration
      dependent contractions of the detrusor; the contraction led to an irreversible
      tachyphylaxis. Muscle desensitized to PTX continued to respond to acetylcholine
      (ACh) and excess K+ but the contractions were reduced compared to pre-PTX
      contractions. 3. Contractions evoked by PTX were not affected by the presence of
      atropine (10 microM), indomethacin (10 microM) or tetrodotoxin (0.5 microM) but
      were greatly reduced by nifedipine (3 microM) and by the absence of K+. PTX could
      not evoke contractions in the absence of Ca2+ or in tissues depolarized by
      exposure to excess K+. 4. PTX abolished the neurogenic contractile responses to
      electrical field stimulation (EFS). 5. Combined treatment with atropine (10
      microM) plus nifedipine (3 microM) abolished contractile responses to EFS and
      greatly reduced the contractile response to PTX. 6. The contractile response to
      PTX (100 nM) was reduced following exposure of the muscle to alpha, beta
      methylene ATP. 7. Exposure to PTX (100 nM) for 1-3 h reduced both the ACh content
      of the detrusor (by more than 80%), and the immunoreactivity of neuropeptide Y
      containing nerve fibres compared to control. 8. It is concluded that the primary
      effect of PTX is to promote the release of endogenous motor transmitters, leading
      to their eventual depletion.

PMID- 1356560
TI  - The effects of combined angiotensin converting enzyme inhibition and beta
      adrenoceptor blockade on plasma renin activity in anaesthetized dogs.
AB  - 1. The effects of beta-adrenoceptor blockade on the changes in plasma renin
      activity (PRA) following angiotensin enzyme (ACE) inhibition were investigated in
      pentobarbitone-chloralose anaesthetized dogs. 2. ACE-inhibition, with enalapril
      (2 mg kg-1), caused a significant reduction in systemic arterial blood pressure
      (BP) with little or no effect on cardiac function, and a significant elevation of
      plasma renin activity (PRA). By contrast beta-adrenoceptor blockade with atenolol
      (1 mg kg-1), caused a similar reduction in BP but in addition, significantly
      reduced cardiac function and PRA. 3. A combination of enalapril with atenolol,
      caused a significant reduction in BP, cardiac function and PRA, hence there was
      no elevation of PRA, as was seen following ACE-inhibition with enalapril alone.
      4. The observations with beta-adrenoceptor blockade alone, show that there is an
      important homeostatic role for the renal sympathetic innervation, mediated by
      beta-adrenoceptors, in controlling basal renin levels. Furthermore, the renal
      sympathetic innervation appears to be an important contributor to the renin
      release caused by an ACE-inhibitor as the additional presence of a beta
      adrenoceptor blocking agent will prevent this release. 5. BW B385C (2 mg kg-1),
      which combines both ACE-inhibition and beta-adrenoceptor blocking properties,
      also produced reductions in BP and cardiac function similar to those seen with
      the enalapril/atenolol combination. In addition, for an equivalent degree of ACE
      inhibition by BW 385C, to that seen with enalapril alone, the elevation of PRA
      was attenuated. 6. A combination of ACE-inhibition and beta-adrenoceptor blocking
      activity in a single entity, such as BW B385C, therefore also produces a reduced
      renin release when compared with an ACE-inhibitor, such as enalapril. This
      provides further confirmation of the importance of the renal sympathetic
      innervation in the renin response to ACE-inhibition, and supports the concept of
      combining ACEinhibition with beta-adrenoceptor blockade.

PMID- 1356559
TI  - Selective and full beta 1-adrenoceptor agonist action of a catechol derivative of
      denopamine (T-0509) in the guinea-pig cardiac muscle and trachea: comparison with
      denopamine, xamoterol and isoprenaline.
AB  - 1. The pharmacological actions of T-0509, a 3-hydroxy derivative of denopamine,
      were studied in various guinea-pig tissues; these effects were compared with
      those of isoprenaline, denopamine and xamoterol. 2. The intrinsic activities of
      the positive inotropic actions of T-0509, denopamine and xamoterol compared with
      isoprenaline (= 100%) in the papillary muscle were 99%, 83% and 28%,
      respectively, while their relative potencies (EC50 agonist EC50 isoprenaline)
      were 0.23, 33 and 1.4, respectively. The intrinsic activities of T-0509,
      denopamine and xamoterol as positive chronotropic agents in the right atria were
      98%, 69% and 48%, respectively, and their equipotent concentrations (isoprenaline
      = 1) were 0.24, 50 and 4, respectively. 3. The positive chronotropic actions of T
      0509 and denopamine were antagonized by bisoprolol (3 x 10(-8) M), but not by ICI
      118,551 (3 x 10(-8) M). 4. The intrinsic activity of T-0509 in histamine
      contracted tracheae was similar to that of isoprenaline, but its equipotent
      concentration was 38; the effects of both agents were antagonized by ICI 118,551
      (3 x 10(-8) M), but not by bisoprolol (3 x 10(-8) M). Denopamine and xamoterol
      did not show any agonist activity on guinea-pig trachea. 5. Denopamine and
      xamoterol antagonized the positive chronotropic (pA2, denopamine: 6.98,
      xamoterol: 7.75) and tracheal relaxant (pA2, denopamine: 5.39, xamoterol: 6.25)
      effects of isoprenaline. 6. Isoprenaline, T-0509 and denopamine, but not
      xamoterol, contracted the guinea-pig aorta in a decreasing order in the presence
      of propranolol (10(-6) M).7. Based on the above studies, T-0509 appears to be a
      highly selective betaI-adrenoceptor agonist with full agonist properties, while
      denopamine and xamoterol appear to be selective, but partial betaI-adrenoceptor
      agonists.

PMID- 1356561
TI  - Effects of acute and chronic electroconvulsive shock on noradrenaline release in
      the rat hippocampus and frontal cortex.
AB  - 1. Changes in the extracellular content of endogenous noradrenaline (NA) in
      frontal cortex and hippocampus were determined by in vivo microdialysis following
      acute and chronic electroconvulsive shock (ECS) in rats anaesthetized with
      chloral hydrate. 2. Basal release of NA in the frontal cortex (4.9 +/- 0.3
      pg/sample) did not differ significantly from that in the hippocampus (4.6 +/- 0.2
      pg/sample). 3. A single ECS resulted in an increase of NA release in the
      hippocampus (21.1 +/- 1.3 pg/sample) and in the frontal cortex (11.6 +/- 1.2
      pg/sample). In both brain regions extracellular NA had returned to basal values
      within 30 min. 4. Animals were treated chronically with ECS (once per day for
      seven days). Twenty-four h later (day 8), basal release of NA into dialysis
      samples from the frontal cortex was significantly increased (50%) as compared to
      chronic sham controls. Basal release in the hippocampus was not significantly
      different from the sham controls. In the chronic ECS animals the increase in NA
      released in both brain areas following an ECS on day 8 did not differ from either
      the chronic sham controls or from animals given acute ECS. 5. Animals were
      challenged 24 h after eight ECS or sham control treatments (once per day) with
      the alpha 2-adrenoceptor antagonist, idazoxan (10 mg kg-1, s.c.). Idazoxan
      increased NA release in the hippocampus in both groups. There was no difference
      in the magnitude of the response in ECS- and in sham-treated rats.In the frontal
      cortex, idazoxan increased the extracellular NA content in the chronic sham
      controls, but the response to idazoxan was significantly attenuated in the
      chronic ECS animals.6. Chronic but not acute ECS was found to elicit a sustained
      (>24 h) increase in the release of NA in the frontal cortex, but not in the
      hippocampus. The idazoxan data suggest that the increase may be due to a
      downregulation of presynaptic alpha2-adrenoceptors in the frontal cortex. The
      difference in response of these two brain regions to chronic ECS is discussed in
      terms of differences in the regulation of extracellular NA content by uptake and
      autoreceptor activation.

PMID- 1356562
TI  - The effects of idazoxan and other alpha 2-adrenoceptor antagonists on urine
      output in the rat.
AB  - 1. In normally-hydrated Wistar rats the alpha 2-adrenoceptor antagonist, idazoxan
      (1, 3, 10 mg kg-1 i.p.), increased urine output during the 6 h following
      injection. 2. The more selective and specific alpha 2-adrenoceptor antagonist,
      RX811059 (0.3, 1, 3 mg kg-1 i.p.), and the peripherally-acting alpha 2
      adrenoceptor antagonist, L-659,066 (1, 3, 10 mg kg-1 i.p.), had no effect on
      urine output in normally-hydrated animals. 3. In rats given a 25 ml kg-1 water
      load orally, idazoxan (10 mg kg-1, i.p.) produced an initial antidiuretic
      response which was followed by an increase in urine output which was apparent 4
      and 6 h after drug administration. 4. RX811059 (1, 3 mg kg-1 i.p.) and L-659,066
      (3, 10 mg kg-1 i.p.) significantly decreased urine output in water-loaded rats in
      the 2 h after injection. 5. The antidiuretic effects of L-659,066 were attenuated
      in Brattleboro rats which are deficient in vasopressin; only the highest dose (10
      mg kg-1 i.p.) decreased urine output, and this was only a small response in
      comparison with its virtual abolition of urine output in water-loaded Wistar
      rats. 6. The results with the selective alpha 2-adrenoceptor antagonists in
      Wistar and Brattleboro rats suggest that alpha 2-adrenoceptors in the periphery
      may play a physiological role in the control of water balance through a mechanism
      which involves vasopressin. 7. The paradoxical diuretic effects of idazoxan
      contrast with the effects of the other alpha 2-adrenoceptor antagonists and
      therefore may be attributed to a property of this compound unrelated to alpha 2
      adrenoceptor blockade.

PMID- 1356563
TI  - Investigations of the subtype of alpha 2-adrenoceptor mediating contractions of
      the human saphenous vein.
AB  - 1. We have examined the effects of a series of alpha 2-adrenoceptor antagonists
      against isometric contractions to noradrenaline in human saphenous vein, and
      correlated these potencies with affinities for the alpha 2A-ligand binding site
      of human platelet and the alpha 2B-ligand binding site of rat kidney. 2. The
      alpha 2B-selective adrenoceptor antagonists, prazosin, ARC 239 and HV 723 showed
      high, and the alpha 2A-selective antagonist BRL 44408 showed low, potency in
      human saphenous vein. 3. Potency in human saphenous vein correlated better with
      affinity for the alpha 2B-ligand binding site (r = 0.71, n = 12, P less than
      0.01) than with affinity for the alpha 2A-ligand binding site (r = 0.56, n = 12,
      non significant). 4. It is concluded that the postjunctional alpha 2-adrenoceptor
      of human saphenous vein resembles an alpha 2B-ligand binding site more than an
      alpha 2A-ligand binding site.

PMID- 1356564
TI  - Modulation of peristalsis in the guinea-pig isolated small intestine by exogenous
      and endogenous opioids.
AB  - 1. A recording method was developed to measure physiological parameters of the
      preparatory and emptying phases of peristalsis in vitro. This method enabled
      measurement of: the compliance of the intestinal wall during the preparatory
      phase (a reflection of the resistance of the wall to distension); longitudinal
      muscle contraction during the preparatory phase; the threshold volume required to
      trigger the emptying phase; the maximal ejection pressure and the average power
      generated during the emptying phase, which reflects the rate at which the
      intestine performs work. Modulation of these parameters by exogenous and
      endogenous opioids acting at mu, kappa and delta opioid receptors was
      investigated. 2. The compliance of the intestinal wall during the preparatory
      phase was reduced by the mu opioid receptor agonist, [D-Ala2, N-methyl-Phe4, Gly5
      ol] enkephalin (DAMGO) but not by the kappa agonist, dynorphin, or the delta
      agonist, [D-penicillamine2, D-penicillamine5] enkephalin (DPDPE). Reflex
      contraction of the longitudinal muscle during the preparatory phase was inhibited
      by DAMGO, dynorphin and DPDPE. The threshold volume required to trigger the
      emptying phase of peristalsis was increased by DAMGO, dynorphin and DPDPE. 3. The
      maximal ejection pressure generated during the emptying phase was reduced by
      dynorphin and DPDPE, but not by DAMGO. The average power generated by the
      intestine when emptying was not altered by any of the agonists. 4. Electrically
      stimulated contractions of longitudinal muscle in strips of longitudinal muscle
      myenteric plexus were not inhibited by DPDPE. Similarly, DPDPE did not
      significantly inhibit electrically induced contraction of circular muscle in
      strips of circular muscle-myenteric plexus.5. Each of the agonist effects on
      peristaltic parameters was antagonized by the appropriate antagonist:D-Phe-Cys
      Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) (mu), norbinaltorphimine (nor-BNI) (kappa),
      naltrindole(delta).6. It is concluded that mu and kappa agonists act primarily on
      excitatory circular and longitudinal muscle motor neurones. The delta agonist
      probably acts on enteric neurones presynaptic to excitatory circular and
      longitudinal muscle motor neurones.7. Antagonists for mu, delta and kappa
      receptors did not affect any parameters of peristalsis when the intestine emptied
      against a low resistance. However, when emptying against a high outflow
      resistance, the average power generated by the intestine was increased by the
      kappa antagonist, nor-BNI, but not by CTOP or naltrindole.8. It is concluded that
      endogenous opioids appear to have little role in peristalsis when the intestine
      is working against a low outflow resistance. However endogenous opioids, acting
      primarily at kappa receptors,provide a braking mechanism by inhibiting the
      emptying phase of peristalsis in conditions in which the intestine empties
      against a higher resistance.

PMID- 1356565
TI  - Characterization and autoradiographical localization of non-adrenoceptor idazoxan
      binding sites in the rat brain.
AB  - 1. In rat whole brain homogenates, saturation analysis revealed that both [3H]
      idazoxan and [3H]-RX821002, a selective alpha 2-adrenoceptor ligand, bound with
      high affinity to an apparent single population of sites. However, the Bmax for
      [3H]-idazoxan was significantly (P less than 0.01) greater than that for [3H]
      RX821002. 2. In competition studies, (-)-adrenaline displaced 3 nM [3H]-idazoxan
      binding with an affinity consistent with [3H]-idazoxan labelling alpha 2
      adrenoceptors. However, this displacement was incomplete since 23.68 +/- 1.11% of
      specific [3H]-idazoxan binding remained in the presence of an excess
      concentration (100 microM) of (-)-adrenaline. In contrast, unlabelled idazoxan
      promoted a complete displacement of [3H]-idazoxan binding with a Hill slope close
      to unity and an affinity comparable with its KD determined in saturation studies.
      3. Displacement of [3H]-idazoxan binding by the alpha 2-adrenoceptor antagonists
      yohimbine, RX821002 (2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline) and
      RX811059 (2-(2-ethoxy-1,4-benzodioxan-2-yl)-2-imidazoline) was more complex, with
      Hill slopes considerably less than unity, and best described by a two-site model
      of interaction comprising a high and low affinity component. The proportion of
      sites with high affinity for each antagonist was similar (60-80%). 4. The rank
      order of antagonist potency for the high affinity component in each displacement
      curve (RX821002 greater than RX811059 greater than yohimbine) is similar to that
      determined against the binding of [3H]-RX821002 to rat brain, suggesting that
      these components reflect the inhibition of [3H]-idazoxan binding to alpha 2
      adrenoceptors.The remaining component in each displacement curve exhibiting low
      affinity towards these antagonists is attributable to the displacement of [3H]
      idazoxin from a non-adrenoceptor idazoxan binding site (NAIBS) since a comparable
      amount of [3H]-idazoxan binding was not displaced by an excess concentration of (
      )-adrenaline.5. The displacement of [3H]-idazoxan binding by RX801023 (6-fluoro
      (2-(1,4-benzodioxan-2-yl)-2-imidazoline) was also best described by a model
      assuming a two site interaction with 20.07 +/- 3.11% of the sites labelled
      displaying high affinity for RX801023. The Ki of RX801023 for the remainder of
      the sites labelled was similar to its Ki versus [3H]-RX821002, indicating that
      this drug displays improved affinity and NAIBS/z2-adrenoceptor selectivity
      compared with idazoxan.6. In autoradiographical studies, the distribution of 5 nM
      [3H]-idazoxan binding to sections of rat whole brain was consistent with that
      reported from previous studies and resembled the distribution ofM2-adrenoceptors.
      However, when sections of brain were coincubated with concentrations of alpha2
      adrenoceptor agonists or antagonists predicted to saturate alpha2-adrenoceptors,
      there remained distinct areas of binding corresponding to discrete brain nuclei.
      This remaining binding was however displaced by unlabelled idazoxan (3 microM) or
      RX801023 (3 microM) indicative of the labelling of NAIBS.7. Quantitative
      autoradiography of NAIBS revealed several brain nuclei which contained higher
      densities of these sites than alpha2-adrenoceptors, notably the area postrema,
      interpeduncular nucleus,arcuate nucleus, ependyma and pineal gland.

PMID- 1356566
TI  - Effect of alpha 2-adrenoceptor agonists on gastric pepsin and acid secretion in
      the rat.
AB  - 1. The purpose of the present study was to analyze the effects of the alpha 2
      adrenoceptor agonists clonidine, guanabenz, detomidine and medetomidine on pepsin
      secretion in conscious rats provided with gastric chronic fistula and to compare
      this with acid secretion. 2. Basal interdigestive gastric secretion, which is
      mainly neurally driven in the rat, and the secretion directly stimulated by the
      two main stimulants of chief cells, cholecystokinin octapeptide (CCK8) and
      methacholine, were studied. 3. Basal secretion of pepsin and acid was inhibited
      by all four drugs with comparable EC50S. 4. CCK-stimulated pepsin and acid
      secretion was less sensitive than basal pepsin and acid secretion to alpha 2
      adrenoceptor inhibition. 5. Methacholine-stimulated pepsin and acid secretion was
      not changed by clonidine and guanabenz; methacholine-stimulated acid was even
      marginally increased by clonidine. 6. These results do not favour the presence of
      alpha 2-receptors on chief cells in the rat stomach. They rather suggest that
      pepsin inhibition by alpha 2-adrenoceptor agonists is indirect and due to central
      or peripheral inhibition of the discharge of nerve fibres activating pepsin
      secretion.

PMID- 1356567
TI  - Haemodynamic effects of dicentrine, a novel alpha 1-adrenoceptor antagonist:
      comparison with prazosin in spontaneously hypertensive and normotensive Wistar
      Kyoto rats.
AB  - 1. The haemodynamic effects of dicentrine, an aporphine derivative isolated from
      the plant Lindera megaphylla, were investigated and compared with prazosin in
      rats. 2. In anaesthetized normotensive Wistar-Kyoto (WKY) rats, i.v.
      administration of dicentrine (0.1, 0.5, 1.0 mg kg-1) and prazosin (0.01, 0.05,
      0.1 mg kg-1) induced a dose-related reduction of mean arterial pressure (MAP)
      which reached a maximal effect 5-10 min after injection and persisted for 2 h. 3.
      In anaesthetized WKY rats, a higher dose of dicentrine (1.0 mg kg-1, i.v.) did
      not cause any significant changes in heart rate (HR), cardiac output (CO) and
      stroke volume (SV) but markedly increased tail blood flow. In contrast, a higher
      dose of prazosin (0.1 mg kg-1, i.v.) produced a decrease in HR which paralleled
      the time course of the hypotensive response. 4. The hypotensive activity of
      dicentrine was completely abolished by alpha-adrenoceptor blockade. Both
      dicentrine and prazosin significantly attenuated pressor responses to
      noradrenaline but failed, even at maximal hypotensive doses, to impair the
      pressor effects of angiotensin II or vasopressin. These observations suggest that
      dicentrine appears to exert its hypotensive action through alpha 1-adrenoceptor
      blockade. 5. In conscious normotensive and spontaneously hypertensive (SH) rats,
      dicentrine (0.5-2.0 mg kg-1, i.v.) and prazosin (0.05-0.2 mg kg-1, i.v.) also
      evoked dose-related decreases in MAP which were of greater magnitude in SH rats.
      Oral administration of dicentrine (5 and 8 mg kg-1) to conscious SH rats caused a
      hypotensive effect which persisted for over 15 h.6. These results suggest that
      dicentrine may have therapeutic potential as an oral antihypertensive drug via
      alpha-adrenoceptor blockade.

PMID- 1356568
TI  - Strychnine-induced potassium current in CA1 pyramidal neurones of the rat
      hippocampus.
AB  - 1. Direct actions of strychnine (Str) and brucine (Bru) on the dissociated
      hippocampal CA1 neurones of the rat have been investigated with the whole-cell
      mode of the patch-clamp technique. 2. At a holding potential (VH) of -20 mV, both
      Str and Bru elicited outward current at concentrations over 10(-5) M. The
      reversal potential of Str-induced current (EStr) was -77.8 mV, which was close to
      the K+ equilibrium potential (EK = -80.3 mV). The change in EStr for a ten fold
      change in extracellular K+ concentration was 58 mV, indicating that the membrane
      behaves like a K+ electrode in the presence of Str. 3. The concentration-response
      curves for Str and Bru were bell-shaped, and nearly maximum response occurred at
      10(-4) M for Str and 3 x 10(-4) M for Bru. The maximum current amplitude induced
      by Bru was about 80% of that induced by Str. A transient 'hump' current appeared
      immediately after the wash-out of external solutions containing Str and Bru at
      concentrations higher than 10(-4) and 3 x 10(-4) M, respectively. 4. The Str
      induced current (IStr) was antagonized by K+ channel blockers such as Ba2+,
      tetraethylammonium (TEA)-chloride, and 4-aminopyridine (4-AP) in a concentration
      dependent manner. IStr was insensitive to glibenclamide, a blocker of ATP
      sensitive K+ channels. 5. Internal perfusion with 10 mM BAPTA did not affect the
      Str-induced IK. Depletion of the intracellular Ca2+ store by caffeine had no
      effect, indicating that intracellular Ca2+ does not mediate the Str-induced
      activation of K+ conductance.6. Both guanosine-5'-0-3-thiotriphosphate (GTPyS)
      and guanosine-5'-O-thiodiphosphate (GDPPS) suppressed the Str-induced IK, the
      former action appearing more rapidly than the latter. The results suggest that
      the GTP binding proteins are involved in this Str response.7. When neurones were
      loaded with cholera toxin (CTX) or pertussis toxin (PTX) through a patch pipette,
      PTX suppressed the Str response whereas CTX did not, suggesting that G, and/or Go
      might be involved in the Str-induced IK.

PMID- 1356571
TI  - Syndromes of chronic schizophrenia and some clinical correlates.
AB  - Subtypes of the features of chronic schizophrenia were investigated. As in
      previous research, three discrete syndromes were found. These were then related
      to demographic, psychological, and movement-disorder variables. Possible
      pathophysiological mechanisms are discussed in terms of known neostriatal
      functions.

PMID- 1356569
TI  - Prejunctional alpha 2-adrenoceptors in mouse atria function through G-proteins
      which are sensitive to N-ethylmaleimide, but not pertussis toxin.
AB  - 1. The identity of the G-proteins involved in prejunctional alpha 2-adrenoceptor
      signal transduction in mouse atria was examined by use of the G-protein
      inactivators N-ethylmaleimide and pertussis toxin. 2. The alpha 2-adrenoceptor
      partial agonist clonidine (0.03 microM) inhibited the electrical stimulation
      induced (S-I) outflow of radioactivity from mouse atria which were incubated with
      [3H]-noradrenaline and stimulated at 5 Hz. The partial alpha 2-adrenoceptor
      agonist St 363 (10 microM) inhibited the S-I outflow of radioactivity at the
      lower stimulation frequency of 2.5 Hz. The inhibitory effects of these compounds
      were not altered in mice pretreated with pertussis toxin (1.5 micrograms, i.v.).
      3. The alpha 2-adrenoceptor antagonist, idazoxan (0.1 microM), increased the S-I
      outflow of radioactivity from mouse atria stimulated at 5 Hz, and this effect was
      not altered in atria from mice pretreated with pertussis toxin. 4. The inhibitory
      effects of clonidine and St 363 and the facilitatory effect of idazoxan on the S
      I outflow of radioactivity from mouse atria were significantly less in atria
      incubated with N-ethylmaleimide (NEM, 3 microM) for 60 min before the [3H]
      noradrenaline incubation. 5. The results suggest that prejunctional alpha 2
      adrenoceptors in mouse atria function through G-proteins which are NEM-sensitive,
      but pertussis toxin insensitive.

PMID- 1356570
TI  - [3H]-MK 912 binding delineates two alpha 2-adrenoceptor subtypes in rat CNS one
      of which is identical with the cloned pA2d alpha 2-adrenoceptor.
AB  - 1. Simultaneous computer modelling of control and guanfacine-masked [3H]-MK 912
      saturation curves as well as guanfacine competition curves revealed that the
      drugs bound to two alpha 2-adrenoceptor subtypes in the rat cerebral cortex with
      very different selectivities. These alpha 2-adrenoceptor subtypes were designated
      alpha 2A and alpha 2C. The Kd value of [3H]-MK 912 for the alpha 2A-subtype was
      1.77 nM and for the alpha 2C-subtype 0.075 nM; the receptor sites showing
      capacities 296 and 33 fmol mg-1 protein, respectively. The Kds of guanfacine were
      19.9 and 344 nM, respectively. 2. Binding constants of 26 compounds for the two
      rat cerebral cortex alpha 2-adrenoceptor subtypes were determined by simultaneous
      computer modelling of control and guanfacine-masked drug competition curves as
      well as plain guanfacine competition curves using [3H]-MK912 as labelled ligand
      (i.e. a '3-curve assay'). Of the tested drugs WB4101, corynanthine, rauwolscine,
      yohimbine, ARC 239 and prazosin were found to be clearly alpha 2C-selective with
      selectivities ranging from 16 to 30 fold whereas guanfacine, oxymetazoline, BRL
      44408 and BRL 41992 were found to be alpha 2A-selective with selectivities
      ranging from 9 to 22 fold. 3. The Kds of compounds obtained for the cerebral
      cortex alpha 2C-adrenoceptors showed an almost 1:1 correlation with the
      corresponding Kds for alpha 2-adrenoceptors expressed by the pA2d-gene (the rat
      'alpha 2-C4' adrenoceptor) in CHO-cells. The cerebral cortex alpha 2A
      adrenoceptors did not correlate well with the pA2d alpha 2-adrenoceptor Kds. 4.
      In the rat spinal cord [3H]-MK 912 bound to alpha 2A- and alpha 2C-adrenoceptor
      sites with similar affinities as in the cerebral cortex and with densities 172
      and 7.4 fmol mg-1 protein, respectively. Drug affinities for some compounds
      showing major selectivity for alpha 2A- and alpha 2C-adrenoceptors were fully
      compatible with the notion that the spinal cord sites were alpha 2A- and alpha 2C
      adrenoceptors.

PMID- 1356573
TI  - Periodic psychosis associated with the menstrual cycle and increased blink rate.
AB  - The association of a recurrent psychosis in the premenstrual period with an
      increased blink rate is reported. This case adds to evidence supporting a
      hormonal hypothesis of certain psychotic disorders.

PMID- 1356572
TI  - Are there more than two syndromes in schizophrenia? A critique of the positive
      negative dichotomy.
AB  - A sample of 115 DSM-III-R schizophrenics was studied by means of the SANS and
      SAPS. A factor analysis from the nine subscales and two symptoms (inappropriate
      affect and poverty of content) and a review of the previous factor analyses
      suggest that schizophrenic symptoms cannot be appropriately classified into
      positive and negative syndromes. The low internal consistency of the SAPS
      suggests that the positive symptoms are not a homogeneous syndrome. Our results
      fit better with Liddle's model of three syndromes (negative, delusion
      hallucination and disorganisation syndromes). It is argued that we are far from a
      valid classification of schizophrenic symptoms and the positive-negative
      dichotomy appears to be an oversimplification.

PMID- 1356574
TI  - Supersensitivity psychosis with concurrent episodic vomiting.
AB  - A patient with a 15-year history of psychiatric illness treated with neuroleptics
      presented with vomiting, thought alienation, auditory hallucinations and self
      neglect. Dopaminergic supersensitivity was diagnosed and increased doses of
      neuroleptics caused cessation of vomiting. The patient is currently attempting
      discontinuation of neuroleptics.

PMID- 1356576
TI  - Proceedings of the 50th annual congress of the British Institute of Radiology.
      Birmingham, 18-20 May 1992. Abstracts.

PMID- 1356577
TI  - Laparoscopic removal of intraabdominal testis.

PMID- 1356575
TI  - Sex and schizophrenia: vive la difference.

PMID- 1356578
TI  - Localisation of intra-abdominal testis by magnetic resonance imaging.

PMID- 1356579
TI  - Methamphetamine neurotoxicity and striatal glutamate release: comparison to 3,4
      methylenedioxymethamphetamine.
AB  - The effect of repeated administration of either methamphetamine (MA), 3,4
      methylenedioxymethamphetamine (MDMA) or vehicle on the extracellular
      concentrations of glutamate (GLU), aspartate, taurine, dopamine (DA) and its
      metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), was studied in awake, freely
      moving rats using in vivo microdialysis. MA (7.5 mg/kg, i.p.) administered every
      2 h for a total of 3 injections, increased the extracellular concentration of GLU
      in the anteromedial striatum. By contrast, neither vehicle nor MDMA (9.2 and 13.8
      mg/kg) increased GLU efflux following repeated administration. Both MA and MDMA
      increased the extracellular concentration of DA in the striatum. However, the
      cumulative increase in DA was significantly greater in the MDMA treated animals
      as compared to the MA group. The concentrations of DA, serotonin (5-HT) and their
      metabolites were determined in the striatum 7 days following the repeated
      administration of MA, MDMA and vehicle. MA, but not MDMA or vehicle, decreased
      the concentration of DA in the striatum. Conversely, MDMA (13.8 mg/kg) decreased
      the concentration of 5-HT, whereas MA, MDMA (9.2 mg/kg) and vehicle had no effect
      on striatal 5-HT content. These data are suggestive that the long-term (7 day) DA
      neurotoxicity produced by the repeated administration of MA is mediated, in part,
      by a delayed increase in extracellular concentrations of GLU. In contrast,
      repeated administration of MDMA, at a dose which produced a long-term (7 day)
      depletion of striatal 5-HT content, had no effect on GLU efflux in the striatum.

PMID- 1356580
TI  - Dopaminergic modulation of striatal neuropeptides: differential effects of D1 and
      D2 receptor stimulation on somatostatin, neuropeptide Y, neurotensin, dynorphin
      and enkephalin.
AB  - Dopaminergic modulation of neuropeptides in rat striatum was investigated by
      examining the effects of prolonged D1 or D2 receptor stimulation on levels of
      somatostatin, neuropeptide Y, neurotensin, dynorphin and enkephalin. Rats with a
      unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway were
      treated for 7 days with either the D1 agonist SKF 38393 (12.5 mg/kg/day) or the
      D2 agonist quinpirole (1 mg/kg/day). Two regimens of agonist treatment were
      compared: continuous infusion via osmotic pump implanted i.p. and intermittent
      (once daily) i.p. injection. Rats were sacrificed 3 h after the last injection
      and peptide levels measured in the striatum bilaterally by radioimmunoassay;
      alterations in peptide content were observed primarily in the denervated
      striatum. In comparison to values from lesioned, vehicle-treated controls,
      intermittent administration of SKF 38393 reduced somatostatin and neuropeptide Y
      (down 61% and 57%, respectively), increased neurotensin (up 105%) and dynorphin
      (up 184%) and had no effect on enkephalin; continuous SKF 38393 decreased
      neuropeptide Y by 39% but did not alter levels of the other peptides. Continuous
      quinpirole elevated somatostatin and neuropeptide Y levels (up 43% and 33%,
      respectively), but reduced the lesion-induced increases in both neurotensin (down
      51%) and enkephalin (down 24%) content. Conversely, intermittent quinpirole
      decreased somatostatin (down 35%) and neuropeptide Y (down 27%), increased
      neurotensin content by 79% and had no effect on enkephalin. Dynorphin levels were
      not altered by either continuous or intermittent quinpirole. These findings
      reveal the complexity of dopaminergic influences on striatal
      neuropeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356581
TI  - Long-lasting abolishment of noradrenaline induced stimulation of oxidative
      metabolism after chronic exposure of developing mouse astrocytes to cocaine.
AB  - Rate of 14CO2 production from [l-14C]glutamate was determined as a measurement of
      oxidative metabolism in developing primary cultures of astrocytes, obtained from
      the neonatal mouse brain and grown in the absence (control) or presence of
      cocaine. From the age of 3 days, the drug-exposed cultures were grown in a tissue
      culture medium containing either 1 or 3 microM cocaine. After 2 months of chronic
      exposure to cocaine the metabolic rate showed an increase of approximately 50%,
      but there was a long lag period (several weeks) before this response occurred. In
      contrast to a marked stimulation of CO2 production when noradrenaline was added
      to untreated cultures of the same age, there was no similar effect of
      noradrenaline on cultures treated with cocaine. After exposure to cocaine for 21
      days (24-day-old cultures), both the enhanced CO2 production and the abolishment
      of the normal response to noradrenaline persisted during 'withdrawal' (cessation
      of drug exposure) throughout the total period investigated, i.e. to an age of 60
      days (corresponding to a withdrawal period of 36 days). The correlation of these
      findings with in vivo data is discussed.

PMID- 1356582
TI  - Interactions of trimethyl tin (TMT) with rat primary astrocyte cultures: altered
      uptake and efflux of rubidium, L-glutamate and D-aspartate.
AB  - Studies were undertaken to assess the effects of trimethyl tin (TMT) on metabolic
      functions in primary neonatal rat cultured astrocytes. Concentrations as low as
      10(-5) M TMT significantly inhibited the initial rate (1 min) of uptake of
      86RbCl, used as a tracer for K+. TMT also markedly inhibited the initial rate (1
      min) of Na(+)-dependent uptake of L-[3H]glutamate and D-[3H]aspartate, and
      stimulated the release of intracellular 86Rb+, -[3H]glutamate and D-[3H]aspartate
      in a dose-dependent fashion. These observations support the hypothesis that the
      astrocyte plasma membrane is potentially an important target for TMT's toxic
      effect and specifically that small concentrations of this organometal can inhibit
      the ability of astrocytes to maintain a transmembrane K+ gradient. This would be
      expected to compromise the ability of astrocytes to control extracellular K+
      either by spatial buffering or active uptake, and exacerbate on-going swelling.
      Increased levels of glutamate and aspartate in the extracellular fluid upon
      release from astrocytes may play an important role in TMT neurotoxicity.

PMID- 1356583
TI  - Further pharmacological characterization of [3H]idazoxan binding sites in rat
      brain: evidence for predominant labeling of alpha 2-adrenergic receptors.
AB  - In addition to binding to alpha 2-adrenergic receptors, the antagonist
      [3H]idazoxan has been reported to bind to non-adrenergic sites in a number of
      tissues and species. In the present study, the pharmacological nature of
      [3H]idazoxan binding sites in rat brain slices has been examined using
      radioligand binding and autoradiographic techniques. In Na2KHPO4 buffer, four
      drugs with high affinity for alpha 2-adrenergic binding sites were potent
      inhibitors of [3H]idazoxan binding, with the rank order of potency being RX821002
      greater than phentolamine greater than yohimbine greater than (-)epinephrine. Non
      linear regression analysis resolved all competition curves into two components,
      with the high affinity site representing the majority of total [3H]idazoxan
      binding. In autoradiographic studies performed in Na2KHPO4 buffer, all alpha 2
      selective ligands displaced greater than or equal to 75% of total [3H]idazoxan
      binding to most brain regions. These findings indicate that the major component
      of [3H]idazoxan binding was to sites that are alpha 2-adrenergic in nature.
      [3H]Idazoxan binding was also examined in glycylglycine buffer. In contrast to
      binding in Na2KHPO4 buffer, the proportion of low affinity sites was
      significantly increased in glycylglycine buffer. Autoradiographic studies
      confirmed these findings. These pharmacological data are consistent with our
      previously reported conclusions that, under appropriate assay conditions,
      [3H]idazoxan predominantly labels alpha 2-adrenergic binding sites in rat brain.
      These sites are widely distributed and have pharmacological characteristics
      consistent with those previously reported for alpha 2A-adrenergic receptors.

PMID- 1356584
TI  - [3H]linopirdine (DuP 996) labels a novel binding site in rat brain involved in
      the enhancement of stimulus-induced neurotransmitter release: autoradiographic
      localization studies.
AB  - A novel high-affinity binding site for linopirdine (DuP 996; 3,3-bis(4
      pyrindinylmethyl)-1-phenylindolin-2-one), a cognitive enhancer which improves
      learning and memory in rodents and primates, has recently been identified in rat
      brain homogenates. [3H]Linopirdine binding sites were localized in rat brain
      using in vitro labeling, light microscopic autoradiography. Highest densities of
      binding sites were present in the hippocampus (CA1 to CA3 pyramidal cell layers
      and the granule cells of the dentate gyrus), the cerebral cortex (lamina IV), the
      dorsal raphe nucleus and the interpeduncular nucleus. Moderate densities were
      present in the olfactory bulb, olfactory tubercle, amygdala, subiculum and medial
      habenular nucleus. Lower levels of binding were present in the caudate/putamen,
      thalamus and hypothalamus. The localization of [3H]linopirdine binding sites in
      brain areas implicated in cognitive processes and affected in Alzheimer's disease
      suggest that ligands for this binding site may have therapeutic potential for the
      treatment of cognitive deficits seen in dementia.

PMID- 1356585
TI  - The D1 agonists SKF 82958 and SKF 77434 are self-administered by rats.
AB  - The reported failure of the prototypical (but partial) D1 agonist SKF 38393 to
      support self-administration behavior contradicts hypotheses of D1-mediated
      reinforcement. Here we demonstrate that rats will readily self-administer two SKF
      38393 analogs, the partial D1 agonist SKF 77434 and the full D1 agonist SKF
      82958; both compounds produce inverted U-shaped dose-response curves. When
      compared to the parent compound, both analogs display enhanced lipophilicity and
      somewhat decreased D1/D2 selectivity. It is suggested that these properties,
      rather than partial D1 agonist efficacy, explain the failure of SKF 38393 to act
      as a reinforcer.

PMID- 1356586
TI  - Corticosterone accelerates hypoxia- and cyanide-induced ATP loss in cultured
      hippocampal astrocytes.
AB  - Glucocorticoids potentiate injury to the rodent hippocampus following a variety
      of metabolic insults, including hypoxia/ischemia, both in vitro and in vivo. We
      have examined whether corticosterone (CORT), the principal glucocorticoid in the
      rat, could exacerbate hypoxic energy failure in cultured hippocampal astrocytes.
      Exposure to 6 h of atmospheric hypoxia (100% N2) or to 30 min of cyanide did not
      cause any detectable cell injury, although moderate astrocyte damage did occur
      alter 6 h of hypoxia in the absence of glucose. Both cyanide and hypoxia
      significantly reduced astrocyte ATP content, a decline that was further reduced
      when glucose was omitted. A 30 min exposure to 100 microM glutamate elevated ATP
      content under normoxic conditions but enhanced the cyanide-induced loss of ATP. A
      24 h pre-treatment with CORT did not influence normoxic ATP levels but
      potentiated the loss of ATP following both cyanide and hypoxia. CORT also
      exacerbated the loss of ATP seen after combined exposure to cyanide and
      glutamate, as well as that following cyanide + 0 mM glucose. These results
      indicate that both CORT and glutamate can potentiate hypoxia-induced energy
      failure in hippocampal astrocytes, albeit by different mechanisms.

PMID- 1356587
TI  - Chronic neuroleptic administration decreases extracellular GABA in the nucleus
      accumbens but not in the caudate-putamen of rats.
AB  - The extracellular levels of gamma-aminobutyric acid (GABA) in the caudate-putamen
      and the nucleus accumbens of rats following administration of haloperidol
      decanoate, fluphenazine decanoate, or vehicle for 8 months were assessed using
      intracranial microdialysis. Basal levels of extracellular GABA were significantly
      decreased in the nucleus accumbens of both neuroleptic-treated groups while
      levels of GABA in the caudate-putamen were not significantly different between
      groups. These results provide evidence for selective chronic neuroleptic-induced
      effects on in vivo GABA function in different terminal regions containing
      dopamine receptors.

PMID- 1356588
TI  - Modulation of morphine antinociception by antagonism of H2 receptors in the
      periaqueductal gray.
AB  - To determine the brain site of action of the H2 receptor antagonist tiotidine as
      an inhibitor of systemic morphine (MOR) antinociception, the effects of
      intracerebral microinjections of this drug were studied on this response in rats.
      As assessed on the hot plate test, microinjections of tiotidine (1 ng in 0.5
      microliter) into the ventral lateral periaqueductal gray at the level of the
      dorsal raphe (PAG/DR) attenuated MOR-induced antinociceptive responses 10-15 min
      later, but potentiated these responses when tested 20-30 min after its
      administration. This treatment had neither effect in the absence of MOR. In
      contrast, intracerebral tiotidine had no effects on tail flick responses in the
      presence or absence of MOR. Intracerebral tiotidine reduced by about 50% the
      antinociception induced by systemic MOR (5.6 and 10 mg/kg), resulting in a
      parallel, rightward shift in the MOR dose-response curve. When testing occurred
      with a fixed dose of MOR at a fixed time interval, tiotidine dose-response curves
      were U-shaped, an effect postulated to result from the separate inhibitory and
      stimulatory mechanisms found at different times. Intracerebral mapping studies
      showed that the attenuation of MOR antinociception by tiotidine given into the
      PAG/DR was not reproduced by tiotidine injections into adjacent rostral, caudal,
      dorsal or ventral areas. Taken with previous studies showing that: (1) both MOR
      and histamine (HA) induce antinociception when given into the PAG/DR, and (2)
      systemic MOR releases HA in the PAG, the present results strongly suggest that
      systemic MOR attenuates supraspinally organized responses to phasic, thermal
      nociceptive stimuli by mechanisms that include PAG HA release and subsequent
      activation of PAG H2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356590
TI  - Alpha 1-adrenergic agonists act on the ventromedial hypothalamus to cause
      neuronal excitation and lordosis facilitation: electrophysiological and
      behavioral evidence.
AB  - To see if activation of central alpha 1-adrenergic receptors can cause
      facilitation of lordosis in rats, the behavioral effects of centrally
      administered alpha 1-agonists, methoxamine (MA) and phenylephrine (PhE), and
      related agents were studied. In ovariectomized rats treated with estrogen,
      infusion of MA, PhE, or a beta-agonist isoproterenol, into the lateral ventricle,
      or bilateral infusions of MA or PhE into the ventromedial hypothalamus (VMH)
      facilitated lordosis. Conversely, intra-VMH infusion of the alpha 1-antagonist
      prazosin (PZ) inhibited lordosis. Intra-VMH infusion of isoproterenol or an alpha
      2-agonist clonidine, had no effect. Neither was the intra-VMH infusion of MA
      effective if: (i) the rats were not primed with estrogen; (ii) the tips of the
      cannulae were outside the VMH; or (iii) it was preceded by an intra-VMH infusion
      of the alpha 1b-antagonist, chloroethylclonidine (CEC). These results not only
      verify implications from recent studies that alpha 1-receptors in the
      hypothalamus are important for lordosis facilitation, but further show that the
      adrenergic facilitatory effect are: (i) mediated specifically by alpha 1b-subtype
      of the alpha 1-receptor, (ii) estrogen-dependent, and (iii) site-specific to VMH.
      To investigate neural mechanisms potentially underlying the lordosis-facilitating
      effect of alpha 1-activation, the actions of MA and PhE on the electrical
      activity of single neurons of the ventromedial nucleus of the hypothalamus (VMN)
      in vitro were studied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356589
TI  - Inhibitory effect of CCK-8 and ceruletide on glutamate-induced rises in
      intracellular free calcium concentrations in rat neuron cultures.
AB  - To study the mechanism by which cholecystokinin octapeptide (CCK-8) and its
      potent analogue, ceruletide, prevent glutamate-induced neuronal cell death in rat
      neuron cultures, we examined the effect of both peptides on glutamate-induced
      increases in the intracellular free calcium concentrations ([Ca2+]i), which are
      known to be a crucial trigger of the neurodegeneration induced by glutamate. CCK
      8 itself did not alter [Ca2+]i in rat neuron cultures. Glutamate increased
      [Ca2+]i in neuron cultures rapidly and markedly. CCK-8 and ceruletide
      significantly suppressed the increases in [Ca2+]i induced by glutamate. The
      maximum inhibitory effects of CCK-8 and ceruletide at 10(-6) M reached 43 and 46%
      of the response to glutamate, respectively. Gastrin-I and CCK-4 also
      significantly attenuated the increases in [Ca2+]i induced by glutamate. The
      inhibitory effect of CCK-8 was completely blocked by the selective antagonist for
      CCK-B receptors, (+)L-365,260, but not by (-)L-364,718, which is a selective
      antagonist for CCK-A receptors. CCK-8 significantly suppressed [Ca2+]i response
      to kainate and high concentrations of extracellular K+, but not to N-methyl-D
      aspartate. With cultured astrocytes, CCK-8 did not inhibit the increment of
      [Ca2+]i induced by glutamate. These findings clearly demonstrated that CCK-8 and
      ceruletide inhibit glutamate-induced increases in [Ca2+]i in neuron cultures
      through CCK-B receptors, suggesting that CCK-8 may participate in the central
      actions of glutamate.

PMID- 1356591
TI  - Changes in brain catecholamines and dopamine uptake sites at different stages of
      MPTP parkinsonism in monkeys.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to produce
      parkinsonism in primates. We have studied the changes in brain catecholamines and
      the distribution of desipramine insensitive mazindol binding sites in MPTP
      parkinsonian primates at different levels of parkinsonism. Thirty-seven monkeys
      (Macaca fascicularis) were utilized in this study. Twelve naive animals received
      no treatment and served as controls. Twenty-five animals were rendered
      parkinsonian with serial injections of MPTP. All animals were given scored
      neurologic examinations throughout the study. Their movement was quantitated in
      an activity box. The animals were sacrificed 30-360 days after their last MPTP
      injection. The clinical exam of the MPTP parkinsonian monkeys demonstrated mildly
      to severely affected animals. There was an exponential decrease in brain
      catecholamine levels with increased clinical parkinsonism. The MPTP parkinsonian
      animals showed the greatest decrease (67-99.8%) in tissue dopamine levels in the
      caudate nucleus. The putamen followed closely in severity (48-99.8%) and the
      nucleus accumbens was much less affected (0-40%). The percent reduction of
      norepinephrine in the anterior pole of the frontal cortex (0-48%) was similar in
      degree to the decreased dopamine levels in the nucleus accumbens. Mazindol
      binding was decreased 30-98% in the caudate nucleus, 20-97% in the putamen, 0-26%
      in the nucleus accumbens, 80-96% in the substantia nigra pars compacta and 49-94%
      in the ventral tegmental area. In the striatum, the decreased mazindol binding
      was more pronounced laterally and posteriorly. In each animal, there was good
      correlation between tissue dopamine levels and the number of mazindol binding
      sites.

PMID- 1356592
TI  - Differential effect of subthalamic nucleus ablation on dopamine D1 and D2 agonist
      induced rotation in 6-hydroxydopamine-lesioned rats.
AB  - The effect of unilateral subthalamic nucleus ablation on rotation in response to
      dopamine D1 and D2 agonists was examined in rats with a unilateral 6-OHDA lesion
      of the nigrostriatal pathway. Four to five weeks following subthalamic nucleus
      lesion, D2 agonist-induced rotation was reduced in subthalamic nucleus-lesioned
      rats relative to sham controls, although no such reduction in D1 agonist-induced
      circling occurred. However, 1-2 weeks following subthalamic nucleus lesion marked
      reductions occurred in both D1 and D2 agonist-induced rotation in subthalamic
      nucleus lesioned rats compared to sham controls. These results suggest that the
      subthalamic nucleus contributes primarily to the expression of D2-mediated motor
      behaviors, although ablation of the subthalamic nucleus may induce certain time
      dependent compensatory mechanisms in other basal ganglia structures which affect
      D1-mediated actions.

PMID- 1356593
TI  - Excitotoxic lesions of the pedunculopontine tegmental nucleus of the rat. II.
      Examination of eating and drinking, rotation, and reaching and grasping following
      unilateral ibotenate or quinolinate lesions.
AB  - The pedunculopontine tegmental nucleus (PPTg) contains a population of
      cholinergic neurons thought to be part of the ascending reticular activating
      system, and non-cholinergic neurons. In the previous study it was shown that
      various excitotoxins made effective lesions of cholinergic neurons in the PPTg
      but that quinolinate made smaller lesions in the non-cholinergic population,
      making it more selective than any other excitotoxin. The purpose of the present
      experiment was, first, to make lesions of cholinergic neurons throughout the
      length of the PPTg by infusing toxin at two different sites within it; and
      second, to examine simple motor activities in rats bearing either quinolinate or
      ibotenate lesions of the PPTg, and contrast these with the deficits seen after 6
      hydroxydopamine (6-OHDA) induced lesions of mesostriatal dopamine (DA)-containing
      neurons. Post-mortem examination was carried out using choline acetyltransferase
      (ChAT) and tyrosine hydroxylase (TOH) immunohistochemistry, and routine Nissl
      staining. Both quinolinate and ibotenate destroyed approximately 75% of ChAT
      positive neurons in the PPTg, but damage to non-cholinergic neurons (assessed by
      Nissl staining) was twice as great following ibotenate as quinolinate. 6-OHDA
      induced almost complete lesions of mesostriatal DA neurons, assessed by TOH
      immunohistochemistry. DA depleted rats showed deficits in drinking and spilled
      more food in the first 2 weeks after surgery, and were unable to reach or grasp
      food pellets in the staircase test. They also showed strong ipsilateral turning
      in response to amphetamine and contralateral turning to apomorphine. Quinolinate
      lesioned rats had no eating or drinking impairment in the home cage but showed a
      reaching (though not grasping) disability in the staircase test. They had a mild
      ipsilateral bias following amphetamine. Ibotenate lesioned rats, despite having
      larger lesions than the quinolinate, showed no deficits in eating or drinking in
      the home cage, or reaching or grasping disabilities in the staircase test. They
      did have a mild contralateral bias in response to amphetamine. This dissociation
      of the effects of quinolinate and ibotenate lesions of the PPTg is consistent
      with the suggestion that the PPTg has two functionally distinct components, and
      is attributed to the differential lesion of non-cholinergic neurons by the two
      excitotoxins.

PMID- 1356594
TI  - Axonal regeneration after spinal cord transection and reconstruction.
AB  - Following complete transection of the spinal cord, cats were separated into 2
      groups to undergo: (i) surgical reconstruction of the disconnected cord using a
      neuroactive agent mixed into a collagen matrix bridge and omental transposition
      and (ii) cord transection-only. After 90 days, animals were killed and the brain
      and spinal cord were removed for immunohistochemistry. Two weeks prior to
      sacrifice, spinal cord blood flows were measured and the retrograde axonal tracer
      Fluoro-Gold was injected below the transection site. Gross inspection of the
      spinal cords at autopsy showed excellent integration and continuity of the
      collagen matrix bridge with the proximal-distal stumps in the surgical
      reconstruction group. In the transection-only group, the proximal-distal stumps
      were connected by a fibrotic, often tapered in the middle, tissue bridge. Results
      show that omental transposition in the surgical reconstruction group increased
      spinal cord blood flow by 58% when compared to transection-only animals. Fluoro
      Gold was found in mesencephalic and brainstem catecholaminergic and cholinergic
      neurons known to send axons to the spinal cord. Immunohistochemical staining with
      antibodies against catecholamine synthesizing enzymes tyrosine hydroxylase (TH)
      and dopamine-beta-hydroxylase (DBH) showed that surgical reconstruction treated
      cat cords but not transection-only, developed dense bundles of dopaminergic and
      noradrenergic fibers which were present in the collagen matrix bridge and in the
      distal spinal cord. Extension of these catecholaminergic fibers in surgical
      reconstruction treated cats showed maximal outgrowth of 90 mm below the
      transection site when the neuroactive agent 4-aminopyridine was mixed into the
      collagen matrix. In addition, the synaptogenic marker synaptophysin (SYN) was
      observed on preganglionic sympathetic neurons in association with dopaminergic-
      and noradrenergic-containing varicosities distal to the collagen matrix bridge,
      an indication that neo-synaptic contacts may have been made on these previously
      denervated neurons. No TH, DBH or SYN was observed below the transection site in
      transection-only cats. These findings indicate that surgical reconstruction
      treated cords can develop dense supraspinal fiber outgrowth across a treated
      collagen matrix bridge fed by an omental blood supply and that these fibers may
      have made neo-synaptic contacts with appropriate distal spinal cord target
      tissue.

PMID- 1356595
TI  - Presence of a dynorphin-like peptide in a restricted subpopulation of
      catecholaminergic neurons in rat nucleus tractus solitarii.
AB  - Immunofluorescence colocalization techniques were used to examine the extent of
      coexistence of the endogenous opioid peptide dynorphin with catecholamines and
      the related opioid peptide enkephalin within neurons of the rat medulla
      oblongata. Immunoreactivities for dynorphin and the catecholamine-synthesizing
      enzyme tyrosine hydroxylase were found to coexist within a limited subpopulation
      of A2 catecholamine cells, localized to the medial nucleus of the nucleus tractus
      solitarii. Colocalization of the two opioid peptides was found mainly within
      perikarya situated in the medial and ventrolateral nuclei of the nucleus tractus
      solitarii. Triple-labeling studies revealed only rare cases of
      catecholamine/dynorphin/enkephalin coexistence. These data demonstrate that
      dynorphin is present within a restricted subpopulation of catecholamine neurons
      in the dorsal medulla oblongata. In addition, the content of either of the
      opioids enkephalin or dynorphin appears to distinguish subsets of medullary
      catecholamine neurons.

PMID- 1356596
TI  - Decreased striatal D2 dopamine receptors in obese Zucker rats: changes during
      aging.
AB  - The specific binding of [3H]YM-09151-2 was used to investigate the possible
      differences in age-associated changes in striatal D2 dopamine (DA) receptor
      properties in genetically obese (fa/fa) Zucker rats and their lean (Fa/?)
      littermates. The maximal binding sites (Bmax) of D2 DA receptors was found to
      decline with age in both obese and lean rats; the rate of decline in receptor
      Bmax was slightly higher in lean than obese rats. However, the Bmax of D2 DA
      receptor in 6-, 12- and 18-month-old obese rats was significantly lower compared
      to the age-matched lean rats. These data indicate that obesity decreases the
      number of striatal D2 DA receptors without affecting the rate at which receptor
      number decreases with age.

PMID- 1356597
TI  - Adrenergic receptor regulation of amino acid neurotransmitter uptake in
      astrocytes.
AB  - Using culture techniques it has been demonstrated that astroglia possess uptake
      carriers for amino acid neurotransmitters and enzyme systems for inactivation of
      several neurotransmitters. They express membrane receptors functionally coupled
      to second messenger systems and they can regulate the extracellular ionic milieu
      including a clearing of K+ from the extracellular space. With these specific
      functional characteristics and their strategic anatomy the cells might influence
      the passage of information between neurons.

PMID- 1356598
TI  - Selective release of glutamine and glutamic acid produced by perfusion of GLP-1
      (7-36) amide in the basal ganglia of the conscious rat.
AB  - Glucagon-like peptide 1 (GLP-1)(7-36) amide, a member of the family of glucagon
      and related peptides, synthesized by intestinal L cells, has a well-defined
      distribution in rat brain. In addition, specific GLP-1(7-36) amide receptors have
      also been localized in some regions of the brain, which suggests that this novel
      gut-brain peptide has a role in brain function. Accordingly, we investigated the
      effects of this peptide on the release of amino acid neurotransmitters in the
      basal ganglia of conscious rats after its perfusion through a concentric "push
      pull" cannula system with an artificial cerebrospinal fluid. To obtain stable
      basal levels of amino acids, the basal ganglia were perfused with an artificial
      cerebrospinal fluid for 2 h at a flow rate of 20 microliters/min and then with
      GLP-1(7-36) amide for 10 min, followed by 40 min poststimulation perfusion. GLP
      1(7-36) amide produced an immediate increase (p less than 0.01) of the
      extracellular levels of glutamine and glutamic acid in the basal ganglia. By
      contrast, this peptide has no effect on the levels of aspartic acid, glycine, and
      serine. Because glutamine is a metabolic precursor of glutamic acid and is
      synthesized almost exclusively in astrocytes, these findings suggest a
      stimulatory effect of GLP-1(7-36) amide on astrocytes and/or neurons of the rat
      basal ganglia.

PMID- 1356599
TI  - The alpha 1-blocker dapiprazole inhibits diuresis but not drinking and feeding
      induced by U-50,488H.
AB  - To further explore the interaction between opiates and catecholamines in the
      control of water balance, we studied the effects of the alpha 1-adrenoceptor
      antagonist dapiprazole on the modifications in drinking and diuresis produced by
      U-50,488H (a selective kappa-opiate agonist), morphine, naloxone, and amphetamine
      in rats. Because animals were maintained in a free-feeding paradigm and water
      intake is also controlled by feeding (prandial drinking), food intake was also
      measured. At doses administered (3-6 mg/kg, IP), dapiprazole had no effect on
      basal food and water intake or on diuresis. Nor did it modify changes in feeding
      and drinking produced by U-50,488H, morphine, naloxone, and amphetamine. It did,
      however, antagonize the diuretic effect of both U-50,488H and amphetamine. In
      addition, suppression of diuresis was obtained by combining doses of dapiprazole
      and morphine or naloxone that were devoid of antidiuretic effects when
      administered independently. A further experiment showed that diuresis produced by
      water load was also prevented by dapiprazole. alpha 1-Adrenoceptors thus appear
      to play a role in the regulation of water balance in a condition of free access
      to water, inhibiting diuresis without affecting drinking.

PMID- 1356600
TI  - Iontophoretic effects of sigma ligands on rubral neurons in the rat.
AB  - Iontophoretic application of the sigma ligands, 1,3-di-o-tolylguanidine (DTG),
      dextrallorphan, and (+)-pentazocine reliably inhibited the firing rate of rubral
      neurons. Dextrallorphan inhibited 87% of the neurons tested, DTG inhibited 76%,
      and (+)-pentazocine inhibited 50%. These inhibitions were current dependent and
      occurred without significant changes in spike amplitude or duration, suggesting
      that local anesthetic effects were not involved. In contrast to the other sigma
      ligands, iontophoretic application of (+)-3-PPP in the rat red nucleus resulted
      in very few inhibitions and tended to elicit weak excitations instead. Only 14%
      of rubral neurons were inhibited by (+)-3PPP, while 36% were excited. Although
      unusual, (+)-3-PPP has atypical effects when compared to other sigma ligands in
      numerous functional assays for sigma receptor activity. (+)-3-PPP, therefore,
      appears to have complex effects and may act through nonsigma mechanisms or
      through a different type of sigma binding site than the other compounds. The
      inhibition of firing rate produced by the more typical sigma ligands may
      contribute to the postural changes produced by microinjection of sigma ligands
      into the rat red nucleus.

PMID- 1356601
TI  - Prenatal haloperidol exposure: effects on brain weights and caudate
      neurotransmitter levels in rats.
AB  - Monoamines may exert a trophic effect on early brain development. To assess the
      role of dopamine in prenatal neurological development of the rat, haloperidol
      (HAL) was given in daily 2.5 or 5 mg/kg SC doses to dams over gestational days 6
      to 20. This treatment regime did not enhance fetal mortality, but did produce
      reliable, if modest, stunting of the body and brain weight of offspring. The 5
      mg/kg HAL dose consistently reduced offspring brain weight to roughly 90% of
      controls. This effect was probably permanent, in that it was seen throughout
      maturation and in adults as late as 140 days of postnatal age. Appropriate
      controls showed that this effect was not due to drug-induced reductions in food
      intake, to the presence of HAL in maternal milk, or to behavioral abnormalities
      in HAL-exposed dams. These effects had, at best, modest regional specificity, in
      that most brain regions were affected, independently of degree of dopaminergic
      innervation. Closer investigation of HAL effects on the striatum suggested that
      this permanent weight reduction was not accompanied by alterations in striatal
      concentrations of monoamines, monoamine metabolites, amino acids, choline,
      acetylcholine, DNA, protein, or water. It is concluded that prenatal HAL does
      stunt growth, but that this effect may not involve a direct drug influence
      restricted to the fetal dopamine system in the brain.

PMID- 1356602
TI  - Dopamine D2 receptor antagonists induce immediate early genes in the rat
      striatum.
AB  - The acute effects of dopamine D2 antagonists and agonists on the expression of c
      jun, zif-268, ETR101 and c-fos in the rat striatum were studied. A single
      injection IP of haloperidol (2 mg/kg) or sulpiride (100 mg/kg) produced a rapid
      and transient increase in c-jun, zif-268 and c-fos mRNA. ETR101 was not
      activated. These inductions were dose dependent and were specifically blocked by
      pretreatment with a D2 agonist (1 mg/kg quinelorane). Quinelorane alone had no
      effect. Thus, dopamine D2 receptors inhibit the expression of a particular set of
      immediate early genes in the striatum.

PMID- 1356603
TI  - [Endothelin and acute renal failure: study on their relation and possible
      mechanisms].
AB  - In order to investigate the role of endothelin in the pathogenesis of ARF, we
      determined the plasma endothelin (pET) level in different clinical ARF patients
      and experimental ARF rat models. It was found that pET level was significantly
      higher in hepatic renal syndrome (n = 9, pET 210.1 +/- 32.0 pg/ml), epidemic
      hemorrhagic fever (n = 18, 113.3 +/- 14.86 pg/ml), septic shock ARF (n = 8, 121.5
      +/- 13.5 pg/ml), gentamicin ARF (n = 7, 55.9 +/- 6.23 pg/ml) patients, and in
      HgCl2 ARF (n = 8, 31.75 +/- 3.07 pg/ml), glycerine ARF (n = 8, 44.75 +/- 9.8
      pg/ml) rats, compared with that of normal persons (n = 9, 33.6 +/- 3.08 pg/ml) or
      of normal rats (n = 10, 11.4 +/- 0.98 pg/ml). Both in the patients and animal
      groups, there were a linear relationship between the levels of pET and Scr (r =
      0.603 4 and 0.844, P less than 0.01, respectively). Intrarenal infusion ET in
      dosage of 0.16 micrograms.kg-1/h produced a severe reduction of RPF and GFR in
      the infused kidney, without significant similar changes on the contralateral
      kidney. Pretreated with captopril ameliorated the renal hemodynamic changes
      induced by iv ET (0.67 micrograms.kg-1/h), whereas indomethacin potentiated this
      effect. It is concluded that both circulating or local generated ET during the
      ARF play an important role in the pathogenesis of ARF. RAS and PG might involve
      in its mechanisms.

PMID- 1356604
TI  - Long-acting beta 2-agonists.

PMID- 1356605
TI  - Paget's disease of bone: exploring the questions.

PMID- 1356606
TI  - Dental injuries at the 1989 Canada games: an epidemiological study.
AB  - The management and prevention of dental trauma is an integral part of the medical
      services provided at major athletic events. This paper reviews the organization
      and delivery of the dental services provided at the 1989 Canada Games. The
      nature, incidence and management of the dental problems reported in the
      participant population of 3,411 athletes are also described. During the two-week
      competition, 15 participants were assessed and treated for various dental
      conditions, including hard- and soft-tissue injury of the oral cavity, and
      temporomandibular joint sprain. The sports with the highest incidence of dental
      injury for the male population were wrestling (one per cent) and basketball (0.8
      per cent). For the female population, these sports were basketball (2.5 per cent)
      and field hockey (1.3 per cent). The dental services provided during the games
      included emergency assessment and treatment, fabrication of mouthguards, and in
      service education to medical team members.

PMID- 1356607
TI  - [Survival of Salmonella paratyphi B and Pseudomonas aeruginosa in seawater after
      incubation or washing in the presence of osmolytes].
AB  - The authors have compared the survival in seawater of Salmonella paratyphi B and
      Pseudomonas aeruginosa cells grown at low or high osmolarity, in the presence of
      organic osmolytes: glycine betaine, choline, proline, and glutamate. The four
      substrates enhanced the survival potential of S. paratyphi B while only glycine
      betaine protected P. aeruginosa. In addition only S. paratyphi B cells were more
      resistant after a preliminary growth at high osmolarity. Both bacteria were
      sensitive to osmotic down-shock, sensitization of S. paratyphi B being inversely
      proportional (p greater than or equal to 0.01) to the osmolarity of the medium
      used to wash cells. The transit in wastewater, at low osmolarity, can therefore
      modify the behavior of these pathogens in the marine environment.

PMID- 1356608
TI  - Role of fimbrial adhesins in the pathogenesis of Escherichia coli infections.
AB  - Escherichia coli strains are able to cause intestinal (enteritis, diarrhoeal
      diseases) and extraintestinal (urinary tract infections, sepsis, meningitis)
      infections. Most pathogenic E. coli strains produce specific fimbrial adhesins,
      which represent essential colonization factors: intestinal E. coli strains very
      often carry transferable plasmids with gene clusters specific for fimbrial
      adhesins, like K88 and K99, or colonization factor antigens (CFA) I and II. In
      contrast, the fimbrial gene clusters of extraintestinal E. coli strains, such as
      P, S, or F1C fimbriae, are located on the chromosomes. The fimbrial adhesin
      complexes consist of major and minor subunit proteins. Their binding specificity
      can generally be assayed in hemagglutination tests. In the case of fimbrial
      adhesins of intestinal E. coli strains, the major subunit proteins preferentially
      represent the hemagglutinating adhesins, whereas minor subunit proteins are the
      hemagglutinins of extraintestinal E. coli strains. Recently "alternative" adhesin
      proteins were identified, which have the capacity to bind to eukaryotic
      structures different from the receptors of the erythrocytes. Fimbrial adhesins
      are not constitutively expressed but are stringently regulated on the molecular
      level. Extraintestinal E. coli wild-type strains normally carry three or more
      fimbrial adhesin determinants, which have the capacity to influence the
      expression of one another (cross talk). Furthermore the fimbrial gene clusters
      undergo phase variation, which seems to be important for their contribution to
      pathogenesis of E. coli.

PMID- 1356609
TI  - Hashimoto's thyroiditis with medullary carcinoma.
AB  - The association of Hashimoto's thyroiditis with lymphoma and papillary carcinoma
      has been recognized, but there have been few reports of an association between
      Hashimoto's thyroiditis and medullary carcinoma of the thyroid gland, especially
      in Canada. The authors report three cases, seen in an 18-month period, of
      Hashimoto's thyroiditis and medullary carcinoma in patients whose relatives had
      multiple endocrine neoplasia type II. The findings support the view that the
      thyroiditis occurred in response to the tumour process and not vice versa.

PMID- 1356610
TI  - Assume mantle of leadership and help save the planet, FPs at WONCA conference
      told.

PMID- 1356611
TI  - World conference offered bleak news on smoking in Americas, elsewhere.

PMID- 1356612
TI  - Dermal dendrocytes and T-cells in canine mycosis fungoides. Support for an animal
      model of human cutaneous T-cell lymphoma.
AB  - BACKGROUND: An extensive upper dermal network of human Thy-1+/Factor XIIa+ dermal
      dendrocytes (DD) exists in human mycosis fungoides (MF). METHODS:
      Immunophenotyping and morphologic studies on serial frozen and paraffin sections
      from 15 cases of canine MF were performed to see if a similar network exists in
      this disease, as has been proposed as an animal model of human MF. Primary
      antibodies were anti-human Factor XIIIa, Factor XIIIs, anti-canine Thy-1, CD4,
      CD8, CD18, CD45RA, Class II, MAC387, KP-1, EBM-11, and several other pan-T, pan
      B, and pan monocyte markers. RESULTS: Thy-1+/Factor XIIIa+DD were seen in all
      cases and confirmed on identical cells by double immunofluorescence. These were
      seen throughout the upper dermis, similar to DD in human MF. Canine DD expressed
      the macrophage marker 2A2+, and were Class II+, CD4+, CD8-, CD18+, EBM11-, Factor
      XIII-, MAC387-, and KP-1. Epidermal and dermal lymphocytes in canine MF were Thy
      1-, CD4+, CD8-, CD18+, CD45RA-, EBM11-, MAC387-, Factor XIIIa-, Factor XIIIs- in
      some cases, whereas others had a predominance of CD8+ lymphocytes. CONCLUSIONS:
      Thus, canine MF is immunophenotypically similar to human MF. Additional support
      for this disease as a model of human MF is demonstrated by the rich network of
      Thy-1+/Factor XIIIa+ DD in the upper dermis of canine MF similar to human MF.

PMID- 1356614
TI  - Attenuation of preneoplastic lesion development by dietary protein intervention:
      apparent persistence and regression.
AB  - The effects of feeding high protein diets that promote the development of
      aflatoxin B1 (AFB1)-induced gamma-glutamyl transpeptidase positive (GGT+)
      preneoplastic lesions were examined in Fischer 344 (F344) rats. After
      administering AFB1 for 2 weeks (initiation), animals were fed diets over four
      successive 3-week periods (promotion). Either a low (5% casein) or high (20%
      casein) protein diet was fed for 3, 6, or 9 weeks before switching to the
      opposite diet to determine whether progressively longer periods of feeding the
      initial diet caused preneoplastic foci to become more refractory to the
      intervention effects of the second diet. The results from animals consuming the
      20% casein diet for progressively longer periods suggest that longer exposure to
      the high protein diet progressively enhances the potential for future lesion
      growth. Results from animals consuming the 5% casein diet for progressively
      longer periods suggest that longer exposure to the inhibitory low protein diet
      progressively inhibits the potential for future lesion growth. These results
      suggest that a high protein diet is a potent promoter of preneoplastic growth and
      that progressively longer exposure to a particular promotive environment
      increasingly attenuates foci response to future dietary intervention.

PMID- 1356613
TI  - Progesterone receptor immunoreactivity in pancreatic endocrine tumors. An
      immunocytochemical study of 156 neuroendocrine tumors of the pancreas,
      gastrointestinal and respiratory tracts, and skin.
AB  - BACKGROUND: The immunoreactivity for progesterone receptors (PR) of the majority
      of endocrine cells of the human pancreas has prompted the authors to investigate
      if PR expression is maintained in pancreatic endocrine tumors and is correlated
      with the main clinicopathologic features of these neoplasms. Furthermore, the
      study has been extended to other neuroendocrine cells and tumors to determine
      whether PR immunoreactivity is a common feature of neuroendocrine cells and
      tumors other than those of the pancreas. METHODS: One hundred fifty six
      neuroendocrine tumors of the pancreas, gastrointestinal and respiratory tracts,
      and skin were immunostained for PR with three different monoclonal antibodies and
      for estrogen receptors (ER). Additional immunostainings for general
      neuroendocrine markers and for pancreatic hormones were performed in selected
      cases. RESULTS: Nuclear immunoreactivity for PR has been documented in the
      neoplastic cells of 56 (58.33%) of 96 pancreatic endocrine tumors. PR
      immunoreactivity was not influenced by the sex and age of the patients or the
      occurrence of a clinical syndrome related to inappropriate hormone secretion.
      Tumors synthesizing pancreatic polypeptide, glucagon, and insulin expressed PR in
      higher percentages (80%, 75%, and 66%, respectively) than those producing other
      pancreatic hormones or those that were not functioning. Irrespective of the
      functionally different tumor types, PR immunoreactivity showed a significant
      correlation (P = 0.0003) with the absence of metastases and the lack of tumor
      invasion of neighboring organs or of large vessels. As opposed to normal and
      neoplastic islet cells, the neuroendocrine cells and tumors of the
      gastrointestinal tract, respiratory tract, and skin did not show any PR
      immunoreactivity, with the single exception of a typical carcinoid tumor of the
      lung. ER were not identified in any pancreatic or extrapancreatic neuroendocrine
      cells or tumors. CONCLUSIONS: Nuclear PR are immunocytochemically detectable in
      most pancreatic endocrine tumors and are correlated significantly to the absence
      of pathologic evidence for malignancy. Conversely, PR expression has not been
      found in normal and neoplastic endocrine cells and tumors investigated.

PMID- 1356615
TI  - Establishment of the human BSMZ breast cancer cell line, which overexpresses the
      erbB-2 and c-myc genes.
AB  - A new cell line, designated BSMZ, was established from a malignant pleural
      effusion from a woman with breast cancer. This line has a doubling time of 27 h
      and has now been cultured for over 120 passages. The large, rounded BSMZ cells
      grow as both a monolayer and as aggregations in suspension. Intracytoplasmic
      lumen, a finding consistent with results from cells derived from mammary tissue,
      was detected on ultrastructural analysis. Injection of BSMZ cells into nude mice
      resulted in the growth of solid tumors 4 weeks after inoculation. The solid tumor
      was identical to the original BSMZ cells in microscopic and electron microscopic
      studies. These cells possess an average of 80 chromosomes. Expression of erbB-2
      and c-myc genes was increased by 10-fold, while there was no detectable
      overexpression of the N-ras and c-myb genes. Southern analysis has revealed
      amplification of the erbB-2 and c-myc loci. The BSMZ cell line may therefore
      provide a useful model for the study of human breast cancer and overexpression of
      the erbB-2 gene.

PMID- 1356618
TI  - The emerging epidemic of non-Hodgkin's lymphoma: current knowledge regarding
      etiologic factors. Proceedings of a workshop. Bethesda, Maryland, October 22-23,
      1991.

PMID- 1356616
TI  - Frequent loss of heterozygosity for loci on chromosome 8p in hepatocellular
      carcinoma, colorectal cancer, and lung cancer.
AB  - Frequent loss of heterozygosity at chromosomal loci in a specific tumor type may
      indicate the presence of a tumor suppressor gene. We have examined loss of
      heterozygosity on chromosome 8p in paired tumor and constitutional DNA from 346
      patients representing seven different types of human cancer. Frequent allelic
      losses were observed in hepatocellular carcinoma (22 of 46 cases, 47.8%), in
      colorectal cancer (12 of 26, 46.2%), and in non-small cell lung cancer (14 of 35,
      40.0%), in contrast to low frequencies detected in breast cancer (5 of 56, 8.9%)
      and renal cell carcinoma (2 of 27, 7.4%). Ovarian cancer and gastric cancer
      showed intermediate frequencies of 33.3% and 22.2%. Subsequent analysis of 120
      hepatocellular carcinomas and 94 colorectal cancers with five polymorphic markers
      along the short arm of chromosome 8 defined commonly deleted regions within the
      same chromosomal interval, 8p23. 1-8p21.3, suggesting that one or more tumor
      suppressor genes for both cancers may be present in that region.

PMID- 1356617
TI  - Cyclophosphamide resistance in medulloblastoma.
AB  - Mechanisms of tumor resistance to 4-hydroperoxycyclophosphamide (4-HC) were
      studied by using a panel of human medulloblastoma cell lines either passaged in
      the laboratory for resistance to 4-HC or established from tumors showing clinical
      resistance to cyclophosphamide. Multiple distinct mechanisms of resistance were
      demonstrated. Daoy (4-HCR), a line that was 6-fold more resistant than Daoy,
      contained elevated levels of aldehyde dehydrogenase (ALDH). Most of the
      difference in sensitivity between the Daoy (4-HCR) and Daoy cell lines was
      abolished when 4-HC was replaced with phenylketocyclophosphamide, a 4-HC analogue
      that cannot be detoxified by ALDH. Thus, elevated levels of ALDH appear to play a
      role in the resistance of Daoy (4-HCR). Several of the cell lines [D283 Med (4
      HCR), D341 Med (4-HCR), Daoy (4-HCR), D458 Med] contained elevated levels of
      glutathione (GSH). No changes in glutathione-S-transferase activity or isozyme
      pattern were observed, but in two of these three lines, the elevation in GSH was
      accompanied by elevated levels of gamma-glutamyl transpeptidase. To confirm the
      role of elevated GSH content in 4-HC resistance, the sensitivity of the cell
      lines to 4-HC was repeated after depletion of GSH by treatment with L-buthionine
      S,R-sulfoximine. In medulloblastoma cell lines without other mechanisms of
      resistance, a linear relationship was seen between GSH content and resistance to
      4-HC. Moreover, cells with GSH content greater than 5 nmol/mg protein and no
      other overriding mechanism of resistance could be sensitized to 4-HC treatment
      with L-buthionine-S,R-sulfoximine. Finally, D283 Med (4-HCR) cells had mild
      elevations in both ALDH and GSH content, but were resistant to
      phenylketocyclophosphamide and were not significantly sensitized by L-buthionine
      S,R-sulfoximine. This cell line appears to demonstrate a third mechanism of
      resistance to 4-HC. These results suggest that 4-HC resistance in medulloblastoma
      can be multifactorial.

PMID- 1356619
TI  - Characterization of tumor cell resistance to 4'-deoxy-4'-iododoxorubicin
      developed in Ehrlich ascites cells in vivo.
AB  - Reduced drug accumulation is the most common functional change accompanying
      development of P-glycoprotein-associated multidrug resistance. One of our
      laboratories showed earlier that the anthracycline analogue 4'-deoxy-4'
      iododoxorubicin (DIDOX) was accumulated to identical levels in Ehrlich ascites
      tumor (EHR2) and daunorubicin (DNR)-resistant EHR2/DNR+ cells (E. Friche, P. B.
      Jensen, T. Skovsgaard, and N. I. Nissen, J. Cell. Pharmacol., 1:57-65, 1990). In
      this communication, we show that weekly treatment of EHR2-bearing mice with 4, 8,
      or 12 mg of DIDOX/kg/week led to the development of three DIDOX-resistant cell
      lines, EHR2/DIDOX-1, EHR2/DIDOX-2, and EHR2/DIDOX-3. The levels of DIDOX
      accumulation and retention and its outward transport were similar in the drug
      sensitive and three drug-resistant cell lines. By contrast, the accumulation of
      the active DIDOX metabolite, 13-dihydro-DIDOX (13-OH-DIDOX), the parent compound
      doxorubicin, and daunorubicin were all decreased in proportion to the resistance
      of the cells. In EHR2/DIDOX-3 cells, the reduction in daunorubicin accumulation
      coincided with the development of P-glycoprotein as demonstrated by Western blot
      and flow cytometry with C219 antibody. DIDOX had no effect on the photolabeling
      of P-glycoprotein by [3H]azidopine, whereas 13-OH-DIDOX inhibited this labeling
      in a concentration-dependent manner. Subsequent analysis of topoisomerase II
      activities and amounts in EHR2/DIDOX-3 cells revealed decreased DNA topoisomerase
      II catalytic activity. The amounts of immunoreactive DNA topoisomerase II from
      EHR2/DIDOX-1, EHR2/DIDOX-2, and EHR2/DIDOX-3 cells were about 89%, 73%, and 52%,
      respectively, of that seen in the drug-sensitive cells. We also found that
      teniposide stabilized DNA-protein complexes in EHR2/DIDOX-3 but they never
      reached the level seen in EHR2 cells. Because it has been reported that DIDOX is
      rapidly metabolized to 13-OH-DIDOX, we postulate that the development of
      resistance to DIDOX in vivo is due in part to its metabolite, 13-OH-DIDOX, which
      is a substrate for plasma membrane glycoprotein, and in part to DIDOX, which is
      an inhibitor of topoisomerase II.

PMID- 1356620
TI  - N-(4'-hydroxyphenylacetyl)palytoxin: a palytoxin prodrug that can be activated by
      a monoclonal antibody-penicillin G amidase conjugate.
AB  - Palytoxin (PTX), one of the most toxic nonprotein molecules known, is cytotoxic
      at picomolar concentrations against a wide variety of cell types. In contrast to
      most cytotoxins, PTX exerts its activity extracellularly. A method for targeting
      PTX to tumor cells is described in which a monoclonal antibody-enzyme conjugate
      activates a PTX prodrug at surfaces of tumor cells. The prodrug, N-(4'
      hydroxyphenylacetyl)palytoxin (NHPAP), was prepared by reacting PTX with an
      active ester of 4-hydroxyphenylacetic acid. NHPAP was 1000 times less toxic than
      PTX to a panel of carcinoma and lymphoma cell lines. The cytotoxic activity of
      the combination of penicillin G amidase from Escherichia coli with NHPAP was
      equal to PTX. Two cell lines that were multidrug resistant showed no enhanced
      resistance to NHPAP +/- penicillin G amidase. Immunologically specific activation
      of NHPAP took place when H2981 cells (L6 antigen positive) were treated with the
      monoclonal antibody conjugate L6-penicillin G amidase followed by NHPAP. This
      system is distinguished from other prodrug activation schemes, since the released
      drug exerts its activity extracellularly, has high potency, and may be able to
      overcome the multidrug resistant phenotype.

PMID- 1356621
TI  - Increased inosine-5'-phosphate dehydrogenase gene expression in solid tumor
      tissues and tumor cell lines.
AB  - Inosine-5'-phosphate (IMP) dehydrogenase, a regulatory enzyme of guanine
      nucleotide biosynthesis, may play a role in cell proliferation and malignancy. To
      assess this role we examined IMP dehydrogenase expression in a series of human
      solid tumor tissues and tumor cell lines in comparison with their normal
      counterparts. Increased IMP dehydrogenase gene expression was observed in brain
      tumors relative to normal brain tissue and in sarcoma cells relative to normal
      fibroblasts. Similarly, in several B- and T-lymphoid leukemia cell lines,
      elevated levels of IMP dehydrogenase mRNA and cellular enzyme were observed in
      comparison with the levels in peripheral blood lymphocytes. These results are
      consistent with an association between increased IMP dehydrogenase expression and
      either enhanced cell proliferation or malignant transformation.

PMID- 1356622
TI  - Decreased P-glycoprotein expression in multidrug-sensitive and -resistant human
      myeloma cells induced by the cytokine leukoregulin.
AB  - Modulation of the expression of P-glycoprotein, a plasma membrane protein
      associated with multidrug resistance, was examined in drug-sensitive and drug
      resistant tumor cells treated with leukoregulin, a M(r) 50,000 cytokine from
      human lymphocytes that rapidly permeabilizes the plasma membrane of many tumor
      cells facilitating the uptake of doxorubicin and other tumor-inhibitory
      antibiotics. P-glycoprotein expression was measured flow cytometrically by the
      binding of C219 or MRK16 monoclonal antibody to multidrug-sensitive human K562
      erythroleukemia and 8226/S myeloma cells, compared to multidrug-resistant
      8226/DOX40 myeloma cells. Cells were treated for up to 2 h with up to 80 units of
      leukoregulin/ml or one of a variety of unrelated cytokines including interleukin
      1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, colony-stimulating
      factor, macrophage colony-stimulating factor, granulocyte macrophage colony
      stimulating factor, tumor necrosis factor alpha, gamma-interferon, alpha
      interferon, epidermal growth factor, platelet-derived growth factor AA, platelet
      derived growth factor BB, insulin-like growth factor I, insulin-like growth
      factor II, fibroblast growth factor, or transforming growth factor beta.
      Leukoregulin caused a concentration-dependent decrease in P-glycoprotein
      expression; however, P-glycoprotein expression was unaffected by the other
      cytokines (< 12% decrease in expression). Leukoregulin-induced membrane
      permeabilization, determined flow cytometrically by intracellular fluorescein
      efflux, and decreased P-glycoprotein expression occurred simultaneously within 15
      min in drug-sensitive and -resistant cells. Enhanced doxorubicin uptake, measured
      flow cytometrically by doxorubicin influx, was also present within 15 min.
      Leukoregulin enhancement of doxorubicin uptake and increased membrane
      permeability varied directly with the decrease in P-glycoprotein expression.
      Leukoregulin in combination with doxorubicin enhanced the inhibition of cell
      proliferation in 8226/DOX40 multidrug-resistant cells over expressing P
      glycoprotein. In contrast, combined treatment of HL-60/MX2 multidrug-resistant
      human promyelocytic leukemia cells that do not overexpress P-glycoprotein in
      association with their multidrug resistance resulted in no greater growth
      inhibition than observed with HL-60/MX2 cells treated with doxorubicin alone.
      This is the first demonstration that a naturally occurring macromolecule with
      anticancer activities can modulate the expression of P-glycoprotein concomitant
      with enhanced drug uptake and inhibition of cell proliferation.

PMID- 1356623
TI  - Inhibitory effect of somatostatin analogue RC-160 on the growth of hepatic
      metastases of colon cancer in rats: a study with magnetic resonance imaging.
AB  - The effect of somatostatin analogue RC-160 on the growth of hepatic metastases of
      colon cancer was investigated in rats using magnetic resonance imaging.
      Experimental liver metastatic tumors were established in syngeneic BDIX rats
      after intrasplenic injection of DHD/K12 colon adenocarcinoma cells. Each rat with
      implanted liver tumors received s.c. injections of somatostatin analogue RC-160
      (50 micrograms/kg) or the vehicle (control) twice a day for 4 weeks, starting 3
      weeks after tumor inoculation. During the treatment with RC-160, the growth of
      liver tumors was studied quantitatively by measuring liver tumor volumes in vivo
      with magnetic resonance imaging at intervals of 7 days. Chronic administration of
      RC-160 inhibited the growth of hepatic metastases of colon cancer in rats.
      Significant inhibition of liver tumor growth in RC-160-treated rats was observed
      throughout the treatment. The final liver tumor volume in the treated rats was
      decreased by 56.1% as compared to the controls. The treatment with RC-160 reduced
      the percentage increase in liver tumor volume from 1575 +/- 674% (mean +/- SEM)
      for the control to 1034 +/- 727% in the treated group. The tumor volume doubling
      time in treated rats was 3.7 days longer than the controls. The liver tumor
      growth delay time was 15.1 days. At the end of the treatment, the incidence of
      ascites and the weights of tumorous livers were also decreased by RC-160
      treatment. Administration of RC-160 prolonged the median survival time by 13 days
      in treated rats. In cell cultures, significant inhibitory effects of somatostatin
      14 and RC-160 on the growth of DHD/K12 colon cancer cells were determined by MTT
      assay and [3H]-thymidine incorporation assay, indicating direct effects of these
      peptides on the growth of colon cancer cells in vitro. These data suggest that
      administration of RC-160 could inhibit the growth of colon cancer and their
      hepatic metastases in rats. Somatostatin analogue RC-160 might be considered as a
      potential new agent for the treatment of patients with hepatic metastases of
      colorectal cancers.

PMID- 1356624
TI  - Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse
      correlation to disease progression.
AB  - Data obtained in experimental murine tumors and in clinical specimens of human
      breast cancer have suggested that the nm23 gene may function as a metastasis
      suppressor gene. In this report we examined the nm23 mRNA level in tumor tissue
      obtained from distant metastases in 33 patients with malignant melanoma. The gene
      was differentially expressed in the tumors with a 20-fold range in hybridization
      intensities. The levels of nm23 mRNA in benign nevi obtained from 12 of the 33
      patients were relatively low, with a mean value of 17% of that in the melanomas.
      In attempts to relate the level of nm23 expression in the tumor metastases to
      progression of the disease, the time from biopsy of the primary tumor to the
      appearance of metastases was used as a clinical end point. It was found that
      patients developing metastases during the first 2 years after diagnosis had
      significantly lower levels of tumor nm23 expression (56% of the mean value)
      compared to patients with less aggressive disease (164%) (P < 0.0004). In
      concordance with previous data the association found here between low levels of
      nm23 mRNA and the malignant potential of melanomas suggests that the nm23 gene
      may be implicated in the mechanism of disease progression in some types of human
      cancer.

PMID- 1356625
TI  - Nonlinkage of 16q markers to familial predisposition to Wilms' tumor.
AB  - Wilms' tumor (WT), a childhood cancer of the kidney, occurs in both familial and
      sporadic forms. Chromosome 11 genes have been implicated in the etiology of WT,
      and mutations in a gene at chromosomal band 11p13, WT1, have been identified in a
      few WT cases. However, 11p13 has been excluded as the site of the predisposition
      mutation segregating in several large WT families, which implies the existence of
      a non-11p familial predisposition gene. Recently, loss of heterozygosity for 16q
      markers located between chromosomal bands 16q13 and 16q22 has been reported in
      approximately 20% of sporadic Wilms' tumors. To determine if this region of 16q
      harbors the non-11p familial WT gene, a genetic linkage study of five WT families
      was undertaken. Using multipoint analyses, we ruled out genetic linkage of
      familial WT predisposition to 16q.

PMID- 1356628
TI  - [Study on the serological typing of patients with epidemic hemorrhagic fever
      (EHF) and host animals in Junan County, Shangdong Province].
AB  - Using hemagglutination inhibition test (HI), we confirmed that Junan County is an
      endemic area of both EHF of R. norvegicus and A. agrarius, which indicated that
      the main host animals were R. norvegicus and A. agrarius in the area. Remarkable
      difference was shown between the infectious rates of pigs from the endemic area
      and that of pigs from the nonendemic area, which suggested that pigs could play
      certain roles in the transmission of EHF. We also proved that the main
      transmission mode of EHF virus in rats was horizontal transmission, and vertical
      transmission in rats also existed.

PMID- 1356627
TI  - Interferon gamma but not tumor necrosis factor alpha decreases susceptibility of
      human renal cell cancer cell lines to lymphokine-activated killer cells.
AB  - Human renal cell cancer (RCC) cell lines, ACHN and KRC/Y, with or without
      exposure to cytokines, were examined for their susceptibility to lymphokine
      activated killer (LAK) cells. Flow-cytometric analysis demonstrated
      constitutional expression of class I antigen on both cell lines, which was
      enhanced by interferon alpha (IFN alpha), IFN gamma and tumor necrosis factor
      alpha (TNF alpha). A 4-h 51Cr-release cytotoxicity assay demonstrated that
      pretreatment of both cell lines with IFN gamma or IFN alpha, but not with TNF
      alpha, decreased their susceptibility to LAK cells. IFN gamma also decreased
      susceptibility to natural killer cells in a 16-h 51Cr-release cytotoxicity assay.
      IFN gamma treatment decreased the susceptibility of ACHN cells in a dose
      dependent manner. "Cold"-target competition assay clearly showed that IFN gamma-
      but not TNF alpha-pretreated cells compete less effectively than do untreated
      target cells. Pretreatment with IFN gamma, however, increased expression of
      intercellular adhesion molecule-1 (ICAM-1) to a degree comparable to that with
      TNF alpha. Northern blot analyses using a 520-base-pair ICAM-1 cDNA as a probe
      demonstrated that more 3.3-kb mRNA is expressed in IFN gamma- and TNF alpha
      pretreated cells. These results suggest that IFN gamma-treated RCC cell lines may
      reduce their ability to be recognized by LAK cells, and that IFN-induced
      protection of RCC cell lines against LAK cells may depend upon a mechanism
      independent of the expression of class I antigens or ICAM-1 on tumor cells.

PMID- 1356626
TI  - Modulation of the antigenic phenotype of human breast carcinoma cells by
      modifiers of protein kinase C activity and recombinant human interferons.
AB  - In the present study we have analyzed the effect of a synthetic protein kinase C
      (PKC) activator 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol (ADMB)
      and the natural PKC-activating tumor-promoting agents 12-O-tetradecanoylphorbol
      13-acetate (TPA) and mezerein on the antigenic phenotype of T47D human breast
      carcinoma cells. All three agents increased the surface expression of the tumor
      associated antigen BCA 225 and various cellular antigens, including HLA class II
      antigens, intercellular adhesion molecule 1 (ICAM-1) and c-erbB-2. Expression of
      the same antigens was also upregulated to various extents in T47D cells by
      recombinant fibroblast (IFN beta) and immune (IFN gamma) interferon. Shedding of
      BCA 225 from T47D cells was induced by TPA, mezerein, IFN beta and IFN gamma,
      whereas ADMB did not display this activity. The ability of ADMB, TPA and mezerein
      to modulate the antigenic phenotype of T47D cells appears to involve a PKC
      mediated pathway, since the PKC inhibitor, H-7, eliminates antigenic modulation.
      In contrast, the ability of IFN beta and IFN gamma to enhance the synthesis,
      expression and shedding of BCA 225, as well as to enhance HLA class II antigens,
      c-erbB-2 and ICAM-1 expression, was either unchanged or modestly reduced by
      simultaneous exposure to H-7. Analysis of steady-state mRNA levels for HLA class
      I antigens, HLA class II-DR beta antigen, ICAM-1 and c-erbB-2 indicated that the
      ability of H-7 to inhibit expression of these antigens in TPA-, mezerein- and
      ADMB-treated cells was not a consequence of a reduction in the steady-state
      levels of mRNAs for these antigens. The results of the present investigation
      indicate that the biochemical pathways mediating enhanced antigenic expression in
      T47D cells induced by TPA, mezerein and the synthetic PKC activator ADMB are
      different from those induced by recombinant interferons. Furthermore, up
      regulation of antigenic expression in T47D cells can occur by a PKC-dependent or
      a PKC-independent pathway.

PMID- 1356629
TI  - Guanylyl cyclase receptors and their endocrine, paracrine, and autocrine ligands.

PMID- 1356630
TI  - Ectopic expression of the floral homeotic gene AGAMOUS in transgenic Arabidopsis
      plants alters floral organ identity.
AB  - The Arabidopsis floral homeotic gene AGAMOUS (AG) is required for development of
      the reproductive organs (stamens and carpels). In ag mutants, the loss of AG
      function leads to the conversion of these organs to the perianth organs (petals
      and sepals). In contrast, mutations in another floral homeotic gene, APETALA2
      (AP2), result in the replacement of the perianth organs by the reproductive
      organs. On the basis of these observations, it has been proposed that AG and AP2
      act in an antagonistic fashion. To test this hypothesis, we have studied the
      effects of ectopically expressed AG in transgenic Arabidopsis plants. The flowers
      of the transgenic plants exhibit a range of phenotypes mirroring those of ap2
      mutants. These experiments provide direct evidence of the proposed antagonism
      between AG and AP2 functions, and the results strongly suggest that AG does
      indeed inhibit AP2 function.

PMID- 1356631
TI  - Manipulation of flower structure in transgenic tobacco.
AB  - Genetic studies suggest that three homeotic functions, designated A, B, and C,
      act alone and together to specify the fate of floral organ primordia in distantly
      related dicotyledonous plant species. To test the genetic model, we have
      generated transgenic tobacco plants that ectopically express the AGAMOUS gene
      from Brassica napus, which is necessary for the C function. Flowers on the
      resulting plants showed homeotic transformations of sepals into carpels and
      petals into stamens. These phenotypes are consistent with predictions from the
      genetic model, show that expression of AGAMOUS is sufficient to provide ectopic C
      function, and demonstrate that the structure of flowers can be manipulated in a
      predictable manner by altering the expression of a single regulatory gene.
      Furthermore, the generation of the predicted transformations by ectopic
      expression of the Brassica gene in transgenic tobacco indicates that gene
      functions are interchangeable between phylogenetically distant species.

PMID- 1356632
TI  - T hybridoma alpha/beta gene transfected in a murine T cell hybridoma: role of CD4
      molecule in vitro and in vivo--engraftment in SCID mice induces T cell
      maturation.
AB  - In the present work, we tested in SCID and Balb/c mice the activity of T
      hybridoma transfected with T cell receptor (TCR) alpha/beta chain genes. A T cell
      hybridoma denoted D011107 was used as recipient for transfection of cytotoxic
      KB5C20 TCR alpha/beta heterodimer genes by protoplast fusion or electroporation.
      After transfection, the parental D011107 T cell line reexpressed CD5 and CD4
      surface molecules. In vitro, we noted strong proliferation and unusual cytotoxic
      reactivities against H-2k target cells although the transfected cell line does
      not express the CD8 molecule. The fate of parental and transfected cells was
      examined in severe combined immunodeficient (SCID) and Balb/c mice at Day 16
      after intravenous injection. Cells from bone marrow, thymus, and spleen tissues
      were analyzed by immunofluorescence. The transfected T cell hybridoma was CD3+
      Desire 1+ CD4+ Thy1.2. The SCID mice grafted with the transfected T cell
      hybridoma presented a high percentage of CD3+ (15%), CD4+ (27%), Thy1.2+
      (27.52%), and Desire 1+ (8.74%) cells in the spleen. The percentages of CD3+
      (6.2%) and Thy1.2+ (5.06%) cells in the spleen from SCID mice grafted with
      parental T cell D011107 and from untreated SCID were similar and lower (CD3+,
      3.52%; Thy1.2+, 4.34%). It seems that transfected T cells hybridoma grafted in
      the SCID mice induce significant expression of CD4+ Thy1.2+ Desire 1- cells (17%)
      in the spleen. These results indicate that transfected T cells graft may allow T
      cell differentiation. In Balb/c mice, the percentage of different T cell subsets
      in bone marrow, thymus, or spleen cells in mice injected with transfected T cells
      was similar to that in untreated mice. We did not observe any cytotoxic or
      significant allogeneic proliferation in vitro.

PMID- 1356633
TI  - Monoclonal antibodies targeting murine LFA-1 induce LFA-1/ICAM-1-independent
      homotypic lymphocyte aggregation.
AB  - We have identified three anti-murine LFA-1 alpha monoclonal antibodies (M17/4.2,
      G-48, and FD441.8) which are capable of inducing homotypic aggregation of murine
      T cell lines (3A9 EL-4 cells). The LFA-1-induced aggregation is temperature
      dependent, necessitates metabolic energy, and requires an intact cytoskeleton,
      but is independent of transcription and protein synthesis. The aggregation is
      inhibited in Ca2+ and Mg2+ free media and is also blocked with EDTA and EGTA. The
      aggregation does not involve protein kinase A or C or changes in intracellular
      calcium. The LFA-1 alpha-induced homotypic aggregation is inhibited with LFA-1
      beta antibodies, but not with antibodies targeting ICAM-1, VCAM-1, VLA-4, or CD2.
      3A9 cells do not express the LFA-1 ligand ICAM-1, whereas EL-4 cells express
      moderate amounts of ICAM-1. Thus, targeting LFA-1 alpha with mAb results in
      homotypic aggregation of T cell lines which is independent of ICAM-1/LFA-1
      interactions, but may involve other LFA-1 ligands such as ICAM-2 or ICAM-3.
      Alternatively, LFA-1 may function as a signaling molecule, triggering other yet
      to be defined adhesion molecules to interact.

PMID- 1356635
TI  - Regulation of contact sensitivity reaction: contrasuppressor T cells and
      contrasuppressor factor downregulate efferent T suppressor cells.
AB  - Contact sensitivity (CS) reaction mediated by CD 4+8- Th 1 cells is under the
      control of several antigen-specific regulatory lymphocytes. Reaction is
      downregulated at the induction stage by T afferent suppressor T cells (Ts-aff)
      that prevent immunization and at the effector stage by efferent T suppressor
      cells (Ts-eff) that made immune Th 1 cells inoperative. Both suppressor cells are
      CD 4-8+ Th 1 effector cells and are protected against the suppressive action of
      Ts-eff cells by CD 4+8- contrasuppressor T cells (Tcs). As has been already shown
      there are also regulatory interactions between regulatory cells themselves and Ts
      aff cells in addition to their effect on precursors of Th 1 cells, also
      preventing the induction of Ts-eff cells. The present experiments extend these
      findings and demonstrate that Ts-eff cells are also under negative control of Tcs
      lymphocytes. Likewise, antigen-specific factor produced by contrasuppressor T-T
      cell hybridoma, used in lieu of Tcs cells, impedes the activation of Ts-eff
      cells. In both cases regulation is aimed at the precursors of Ts-eff cells. Our
      experiments demonstrate that the outcome of immunization is dependent not only on
      the balance between immune cells and regulatory cells, but also on interactions
      between regulatory cells themselves.

PMID- 1356634
TI  - Stimulation of IFN-gamma, TNF-alpha, and TNF-beta secretion in IL-2-activated T
      cells: costimulatory roles for LFA-1, LFA-2, CD44, and CD45 molecules.
AB  - Lymphokine-activated killer (LAK) cells are peripheral blood lymphocytes (PBLs)
      that possess the ability to kill target cells in a non-major histocompatibility
      complex (MHC)-restricted manner. Both NK and T cells can be stimulated with
      interleukin-2 (IL-2) to become LAK cells. We previously reported that the
      interaction of LAK cells with tumor cells also induces the secretion of
      interferon-gamma (IFN-gamma). The NK subset of LAK (LAK-NK) cells is stimulated
      by tumor cells to secrete IFN-gamma in a non-MHC-restricted manner while the T
      cell subset of LAK (LAK-T) cells is stimulated to secrete IFN-gamma upon cross
      linking of the T cell receptor (TCR)-CD3 complex. We here report that LAK-T cells
      stimulated with anti-CD3 mAbs and tumor cells secrete two additional cytokines,
      tumor necrosis factor-alpha (TNF-alpha) and TNF-beta/lymphotoxin (TNF-beta). In
      addition, we demonstrate that at least four other structurally unrelated
      molecules, in addition to the TCR-CD3 complex, on LAK-T cells participate in the
      stimulation of IFN-gamma, TNF-alpha, and TNF-beta production. These molecules are
      the lymphocyte function associated antigen-1 (LFA-1), lymphocyte function
      associated antigen-2 (LFA-2), CD44, and CD45. LFA-1 is an integrin, LFA-2 is a
      member of the immunoglobulin supergene family, CD44 is homologous to the
      cartilage link proteins, and CD45 is a tyrosine phosphatase. Ligands to three of
      these molecules have been identified; ICAM-1, LFA-3, and hyaluronic acid binding
      to LFA-1, LFA-2, and CD44, respectively. LFA-1, LFA-2, and CD44 are reported to
      function both as adhesion molecules and as costimulators in resting T cells. Our
      data suggest that these three molecules enhance IFN-gamma, TNF-alpha, and TNF
      beta production by augmenting LAK-T cell to tumor cell adhesion and also by
      functioning as costimulators.

PMID- 1356636
TI  - The induction of arthritis in mice by the cartilage proteoglycan aggrecan: roles
      of CD4+ and CD8+ T cells.
AB  - Peripheral arthritis is produced in BALB/c mice after hyperimmunization with the
      cartilage proteoglycan aggrecan (PG). Adoptive transfer studies have suggested
      the roles of T cells including CD8+ T cells in the disease process. To evaluate
      the roles of CD4+ and CD8+ T cell subsets in vivo in the induction of this
      disease by immunization, PG-immunized mice were treated with isotype-controlled
      rat IgG2b monoclonal anti-CD4 or anti-CD8 antibodies, or were left untreated.
      CD4+ T cell depletion resulted in total inhibition of the disease with markedly
      decreased anti-PG antibody responses. CD8+ T cell depletion, however,
      significantly enhanced the severity of the disease without affecting peak anti-PG
      antibodies, as compared to the control mice. These results demonstrate a crucial
      role for CD4+ T cells in the pathogenesis of this disease. However, CD8+ T cells
      do not seem to be required for the induction of arthritis by immunization but
      instead may play an immunoregulatory role.

PMID- 1356637
TI  - Activation of maternal centrosomes in unfertilized sea urchin eggs.
AB  - Centrosomes are undetectable in unfertilized sea urchin eggs, and normally the
      sperm introduces the cell's microtubule-organizing center (MTOC) at
      fertilization. However, artificial activation or parthenogenesis triggers
      microtubule assembly in the unfertilized egg, and this study explores the
      reappearance and behavior of the maternal centrosome. During activation with
      A23187 or ammonia, microtubules appear first at the cortex; centrosomal antigen
      is detected diffusely throughout the entire cytoplasm. Later, the centrosome
      becomes more distinct and organizes a radial microtubule shell, and eventually a
      compact centrosome at the egg center organizes a monaster. In these activated
      eggs, centrosomes undergo cycles of compaction and decompaction in synchrony with
      the chromatin, which also undergoes cycles of condensation and decondensation.
      Parthenogenetic activation with heavy water (50% D2O) or the microtubule
      stabilizing drug taxol (10 microM) induces numerous centrosomal foci in the
      unfertilized sea urchin egg. Within 15 min after incubation in D2O, numerous fine
      centrosomal foci are detected, and they organize a connected network of numerous
      asters which fill the entire egg. Taxol induces over 100 centrosomal foci by 15
      min after treatment, which organize a corresponding number of asters. The
      centrosomal material in either D2O- or taxol-treated eggs aggregates with time to
      form fewer but denser foci, resulting in fewer and larger asters. Fertilization
      of eggs pretreated with either D2O or taxol shows that the paternal centrosome is
      dominant over the maternal centrosome. The centrosomal material gradually becomes
      associated with the enlarged sperm aster. These experiments demonstrate that
      maternal centrosomal material is present in the unfertilized egg, likely as
      dispersed undetectable material, which can be activated without paternal
      contributions. At fertilization, paternal centrosomes become dominant over the
      maternal centrosomal material.

PMID- 1356639
TI  - [Medullary carcinoma of the thyroid gland and the APUD system].
AB  - Medullary thyroid carcinoma, MTC, accounts for 8-10% of all thyroid malignancies.
      It occurs in the sporadic form (70-75%) and the familial variant (25-30%). In
      familial MTC the autosomal dominant type of heredity is involved. This variant is
      found frequently in association with other endocrine hyperplasias or tumours
      within the framework of the APUD system and is thus an indispensible condition of
      the MEN 2 syndrome, either MEN 2A (MTC and pheochromocytoma and/or
      hyperparathyroidism) or MEN 2B with the frequent concurrent presence of
      pheochromocytoma and a typical phenotype, in particular multiple neurofibromas on
      the lips and tongue. The type of MTC determines also to a certain extent the
      prognosis of the disease. MTC in the framework of MEN 2A are usually most benign,
      while the prognosis is poorest for MEN 2B. The sporadic variant has a poorer
      prognosis, as compared with differentiated thyroid carcinoma. The only effective
      and rational treatment of MTC is radical surgery. In all instances where we
      confirm the diagnosis before surgery we indicate bilateral total thyroidectomy.
      In the familial variant where the tumour is usually multifocal and in both lobes
      this indication is absolute, in sporadic forms with possible early intrathyroid
      dissemination of the primary tumour also to the other side, bilateral surgery is
      also indicated. Moreover we know that a certain ratio of assumed sporadic forms
      are genetically conditioned tumours and thus are familial. The histological
      finding of hyperplasia of the C-cells suggests the familial variant even when
      tumourous transformation did not occur yet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356638
TI  - Comparative analysis of spontaneous mitotic recombination in [cir0] and [cir+]
      strains of the yeast Saccharomyces cerevisiae.
AB  - The influence of the 2 microns plasmid on homologous recombination in the right
      arm of chromosome XV of the yeast Saccharomyces cerevisiae has been examined. No
      differences between spontaneous mitotic recombination rates in [cir0] and [cir+]
      derivatives of two yeast diploid tester strains were detected. In the course of
      analysis an unusually high coincident conversion frequency at ADE2, HIS3, and two
      RFLP loci adjacent to ADE2, was observed. The character of coincident
      homozygotization of linked markers argues for a "break-and-replicate" mechanism
      underlying the coincident conversion events.

PMID- 1356640
TI  - Method for optical resolution of racemic homochlorcyclizine and comparison of
      optical isomers in antihistamine activity and pharmacokinetics.
AB  - A method was developed for semi-preparative scale enantioseparation of racemic
      homochlorcyclizine (HCZ) by high performance liquid chromatography (HPLC) on
      Chiralcel OD column. The best resolution was achieved using an eluent composed of
      n-hexane plus 0.2 M isopropylamine. By this method, about 5.0 mg of racemic HCZ
      could be resolved completely in one run. The optical purity of the enantiomers
      were both greater than 99.9%. The studies of antihistamine activity on guinea pig
      ileum demonstrated that l-HCZ is significantly more potent than d- and racemic
      HCZ. The pharmacokinetics of d- and l-HCZ after oral administration to rats also
      differed. The successful resolution of racemic HCZ permits comparison of the
      pharmacokinetics and antihistamine activity of the enantiomers.

PMID- 1356641
TI  - Studies on antiulcer drugs. III. Synthesis and antiulcer activities of
      imidazo[1,2-a]pyridinylethylbenzoxazoles and related compounds. A novel class of
      histamine H2-receptor antagonists.
AB  - A series of imidazo[1,2-a]pyridinylalkylbenzoxazole derivatives was synthesized
      and tested for histamine H2-receptor antagonist, gastric antisecretory and
      antiulcer activities. Some of 2-amino-6-[2-(imidazo[1,2-a]pyridin-2
      yl)ethyl]benzoxazole derivatives were found to have good pharmacological
      activities. Among them, 2-amino-6-[2-(7-methoxy-3-methylimidazo[1,2-a]pyridin-2
      yl)ethyl] benzoxazole (II-11) and 2-acetamido-6-[2-(7-methylimidazo[1,2-a]pyridin
      2-yl)ethyl] benzoxazole (II-38) showed potent antisecretory and cytoprotective
      activity. The structure-activity relationships of these compounds are discussed.

PMID- 1356642
TI  - Novel phenoxyalkylamine derivatives. VII. Synthesis and pharmacological
      activities of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide
      derivatives.
AB  - To find a novel alpha-blocker with high alpha-blocking selectivity against
      dopamine D2-receptor affinity, we performed structural modification of the
      alkylene chains and the substituents on two benzene rings of 2-alkoxy-5
      [(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives. The modification of the
      alkylene chain between the amino moiety in the center of the molecule and the
      benzene ring (ring A) was found to be the most significant. 5-[2-[[2-(5-Fluoro-2
      methoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzenesulfonamide (II-4), which
      possesses 1-methylethyl as the alkylene chain, exhibited high alpha-blocking
      selectivity as well as potent alpha-blocking activity.

PMID- 1356643
TI  - Development of a highly cardioselective ultra short-acting beta-blocker, ONO
      1101.
AB  - A novel, highly cardioselective ultra short-acting beta-blocker, ONO-1101, has
      been developed for application in the emergency treatment of tachycardia and
      better control of heart rate in surgery. This agent is approximately nine times
      more potent in beta-blocking activity in vivo and eight times more
      cardioselective in vitro than esmolol. This beta-blocking drug has a short
      duration of activity, enabling rapid recovery after cessation of administration
      if side effects occur. It can be used safely in patients suffering from acute
      heart disease and represents a major therapeutic advance in the treatment of
      heart disease.

PMID- 1356644
TI  - Studies on antiulcer drugs. IV. Synthesis and antiulcer activities of imidazo[1,2
      a]pyridinylethylbenzothiazoles and -benzimidazoles.
AB  - A series of 6-[2-(imidazo[1,2-a]pyridin-2-yl)ethyl]benzothiazoles (II) and
      benzimidazole analogues (III) was synthesized and tested for histamine H2
      receptor antagonist, gastric antisecretory and anti-stress ulcer activity. A
      benzimidazole derivative (IIIa) exhibited strong antisecretory activity, whereas
      the corresponding benzothiazole derivative (IIb) lacked this potency in in vivo
      test. In contrast to compound IIIa, however, compound IIb demonstrated good
      inhibition against stress induced ulcer. The structure-activity relationships of
      these compounds are discussed.

PMID- 1356645
TI  - [Polymorphisms of the D13S26 locus in Chinese and its application to linkage
      analysis of Wilson disease].
AB  - The D13S26 locus has been mapped to 13q21.1-q21.2 and is linked with Wilson
      disease gene at a distance of 3.8 centimorgans. The polymorphic alleles detected
      by HphI, EcoRI and BclI at the D13S26 locus are the same in Chinese as in
      Caucasians, but the allele frequencies are quite different. As calculated from 30
      unrelated Chinese individuals, the allele frequencies were as follows: HphI 2.8
      kb(0.47)/2.0kb(0.53); EcoRI 9.0 kb (0.02)/8.0 kb (0.98); BclI 6.3 kb (0.02)/5.6
      kb (0.98). Cosegregation analysis of the D13S26 locus and Wilson disease locus
      was carried out in 3 families with the disease. In one of these families, the
      proband and his younger sister (7-years-old and phenotypically normal) were both
      heterozygous for this site. We predict with 85.6% confidence that the younger
      sister is in the presymptomatic stage of Wilson disease.

PMID- 1356646
TI  - Cumulation and reversal with prolonged infusions of atracurium and vecuronium.
AB  - A randomized, double-blind study was undertaken to compare the tendencies for
      cumulation, and reversal characteristics of atracurium (ATR) and vecuronium (VEC)
      when administered by continuous infusion for long surgical procedures under
      balanced anaesthesia. Eligible subjects were between 50 and 75 yr of age and were
      free of neuromuscular disease. Patients in the ATR group (n = 25) received a
      loading dose of atracurium 0.25 mg.kg-1, followed by an infusion initially set at
      5.0 micrograms.kg-1.min-1. In the VEC group (n = 25) patients received a loading
      dose of vecuronium 0.05 mg.kg-1, followed by an infusion at 1.0 microgram.kg
      1.min-1. During surgery, the infusions of both ATR and VEC were titrated in
      increments or decrements of 12.5% to maintain first twitch (T1) suppression of 90
      95%. Neuromuscular block was measured by recording the integrated evoked
      electromyographic response (EMG) of the first dorsal interosseous muscle in
      response to supramaximal TOF stimuli on the ulnar nerve. The durations of
      infusion were similar for the two groups (164 +/- 42 and 183 +/- 67 min for ATR
      and VEC, respectively). The infusion rates of ATR (mean +/- SD) remained between
      4.0 +/- 0.7 and 5.0 +/- 1.0 microgram.kg-1.min-1 throughout the study period. In
      contrast, a progressive decrease (P less than 0.05) in the infusion rate of VEC,
      from 1.0 to 0.47 +/- 0.13 micrograms.kg-1.min-1, was observed during the study
      period. The number of adjustments required to maintain 90-95% T1 suppression
      decreased between the second and fourth hours of administration, but were similar
      at corresponding times when comparing the two groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1356647
TI  - Haemodynamic changes and oxygen uptake during crossclamping of the thoracic aorta
      in dexmedetomidine pretreated dogs.
AB  - This study was designed to test the hypothesis that the alpha 2 adrenergic
      agonist, dexmedetomidine (DEX), decreases tissue oxygen demand thereby increasing
      tolerance to hypoxic insult. In 17 anaesthetized dogs, cardiac output was
      measured with thermodilution, blood flow through the inferior caval vein was
      determined using an electromagnetic flowmeter, and oxygen consumption was
      calculated by the Fick principle. The animals were divided into three groups:
      control group (n = 5), D3 and D30 groups (n = 6 for each group) treated with two
      doses of DEX (3 micrograms.kg-1 and 30 micrograms.kg-1, respectively) prior to
      aortic crossclamping. Upon crossclamping of the thoracic aorta, the cardiac index
      decreased in all three groups with the largest decrease in the D30 group, and the
      smallest decrease in the control group. Blood flow through the inferior vena cava
      decreased in all three groups of animals while blood flow through the superior
      caval vein increased in the control group, did not change in the D3 group, and
      decreased in the D30 group. Oxygen saturation in mixed venous blood increased in
      the control group, did not change in the D3 group and decreased in D30 group.
      Blood flow and oxygen uptake in the lower part of the body decreased in all
      groups. Oxygen consumption in the upper part of the body decreased equally in all
      three groups. Arterial lactate concentrations increased almost two-fold in the
      control group while it increased by only 30% in animals treated with DEX. A
      lesser increase in lactate concentrations and oxygen extraction in tissues below
      aortic crossclamping is consistent with the hypothesis that DEX decreases tissue
      oxygen requirement which might prove particularly useful in clinical situations
      where tissue hypoxia is expected.

PMID- 1356650
TI  - The 4th International Conference on Treatment of Urinary Tract Tumors with
      Adriamycin/Farmorubicin. Osaka, Japan, 16-17 November 1990.

PMID- 1356649
TI  - Comparative in vitro cytotoxicity of taxol and Taxotere against cisplatin
      sensitive and -resistant human ovarian carcinoma cell lines.
AB  - Using the sulforhodamine B assay, we compared the cytotoxic properties of the
      novel microtubule agent taxol and the semi-synthetic related compound Taxotere in
      nine human ovarian-carcinoma cell lines, including three pairs of cell lines
      rendered resistant to cisplatin or carboplatin. In addition, the cytotoxicity of
      the commonly used anticancer drugs cisplatin and adriamycin and the topoisomerase
      II inhibitor etoposide was determined. The results of continuous drug exposure
      showed that taxol [mean concentration producing 50% growth inhibition (IC50), 1.1
      x 10(-9) M; range, 2.8 x 10(-9)-5 x 10(-10) M and Taxotere (mean IC50, 5.1 x 10(
      10) M; range, 7.2-3.3 x 10(-10) M) were greater than 1,000 times more cytotoxic
      than either cisplatin (mean IC50, 3.1 x 10(-6) M; P less than 0.05) or etoposide
      (mean IC50, 2.3 x 10(-6) M; P less than 0.05) and greater than 100 times more
      cytotoxic than Adriamycin (mean IC50, 6.9 x 10(-8) M; P less than 0.05). Taxotere
      was more cytotoxic than taxol; following continuous exposure, the mean difference
      across the cell lines was 2 orders of magnitude (range, 1.1-3.9 orders of
      magnitude for individual lines). Although this difference did not reach
      statistical significance for any individual cell line (P values ranged from 0.17
      for HX/62 to 0.9 for OVCAR-3), when all IC50 values for the 96-h experiments were
      pooled, Taxotere was found to be significantly more potent than taxol (P = 0.05).
      Following 2 h exposure, the mean cytotoxicity of Taxotere was 3.9-fold greater
      than that of taxol across the nine lines (range, 0.75- to 10-fold; P less than
      0.05 for the CH1 cell line; overall pooled IC50 data, P = 0.05). Although a 71
      fold range of sensitivity to cisplatin was observed across the six parent cell
      lines (IC50 most resistant line/IC50 most sensitive line), this was largely
      abolished by treatment with taxol (5.6-fold range) and Taxotere (2.2-fold range).
      Following continuous exposure of the three pairs of lines exhibiting acquired
      resistance to platinum, no cross-resistance with either Taxotere or taxol was
      found (resistance factors, less than 1.5). In the 41M and 41McisR pair of lines,
      in which previous studies have shown resistance to be due to reduced platinum
      accumulation, taxol and Taxotere exhibited some collateral sensitivity
      (resistance factors, 0.69 and 0.66, respectively). Taxotere and, particularly,
      taxol showed a pronounced concentration times exposure duration (C x T)
      dependence as compared with cisplatin (P less than 0.05).(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1356651
TI  - Inhibition of aflatoxin B1-induced gamma-glutamyltranspeptidase positive (GGT+)
      hepatic preneoplastic foci and tumors by low protein diets: evidence that altered
      GGT+ foci indicate neoplastic potential.
AB  - Previous studies in this laboratory with young Fischer 344 male rats have shown
      that the post-initiation development of aflatoxin B1 (AFB1)-induced gamma
      glutamyltranspeptidase positive (GGT+) hepatic foci was markedly inhibited by low
      protein feeding, even though the energy intake was greater. This dietary effect,
      however, did not necessarily apply to hepatic tumor development. Thus, the
      present investigation was undertaken to examine this dietary effect upon the
      development of hepatic tumors and, is so doing, to determine the correlation of
      foci development with tumor development. Following AFB1 dosing (15 daily doses of
      0.3 mg/kg each), animals were fed diets containing 6, 14 or 22% casein (5.2,
      12.2, 19.1% protein) for 6, 12, 40, 58 and 100 weeks. Foci at 12 weeks and tumors
      at 40, 58 and 100 weeks developed dose-dependently to protein intake. Foci
      development, tumor incidence, tumor size and the number of tumors per animal were
      markedly reduced while the time to tumor emergence was increased with low protein
      feeding. Non-hepatic tumor incidence also was lower in the animals fed the lowest
      protein diet. Foci development indices (foci number, per cent liver volume
      occupied) were highly correlated with tumor incidence at 58 and 100 weeks (r =
      0.90-1.00). Tumor and foci inhibition occurred in spite of the greater energy
      intake.

PMID- 1356652
TI  - Measurement of neutrophil activation and epidermal cell toxicity by palytoxin and
      12-O-tetradecanoylphorbol-13-acetate.
AB  - Palytoxin is a human and mouse skin irritant and complete mouse skin tumor
      promoter that differs from the well-studied phorbol ester class of tumor
      promoters in many respects. In this study, we have found palytoxin to stimulate
      the production of superoxide by isolated human neutrophils using electron
      paramagnetic resonance (EPR) spectroscopy with the spin-trap DMPO. This
      stimulation of oxyradical production by palytoxin is relatively weak, however,
      when compared to that by 12-O-tetradecanoylphorbol-13-acetate (TPA). The maximal
      amount of oxyradicals produced by palytoxin-stimulated neutrophils is 10(-4)
      mumols/10(6) neutrophils, and this stimulation requires nanomolar concentrations
      of palytoxin, with half maximal stimulation at concentrations of approximately 30
      nM. In contrast, the tumor promoter TPA causes human neutrophils to generate in
      excess of 10(-3) mumols oxyradicals/10(6) neutrophils with concentrations as low
      as 1 nM. Toxicity to cultured human epidermal cells was observed at very low
      concentrations of palytoxin, with 50% loss of colony-forming efficiency observed
      at approximately 3 x 10(-13) M. For TPA, 50% loss of colony-forming efficiency
      for cultured epidermal cells requires approximately 5 nM. Thus, although
      palytoxin stimulates superoxide production in isolated neutrophils, epidermal
      cells are sensitive at much lower concentrations and are likely to be the
      important target cell in vivo. This is in contrast to TPA, where neutrophils are
      stimulated at concentrations less than those required to produce pathological
      effects on epidermal cells, suggesting that neutrophils may be an important
      target cell for TPA in vivo.

PMID- 1356653
TI  - Mechanism of hind limb vasoconstriction due to cyclosporin A in the dog.
AB  - Cyclosporin A (CSA) causes an acute vasoconstriction of hind limb arterial
      vessels. To determine the mechanism of action of CSA on the peripheral arterial
      bed, studies were performed on the isolated femoral artery perfused at constant
      flow in 61 dogs. Changes in femoral perfusion pressure reflected variations in
      vascular resistance. Pure powder CSA was dissolved in autologous blood and
      injected at doses of 1, 5, 10, and 20 mg. Infusions of 1 and 5 mg CSA caused
      nonsignificant mean increases of 4 +/- 2 mm Hg (95% confidence interval [CI], 0
      8; p > 0.05) and 10 +/- 4 mm Hg (95% CI, 0-21; p > 0.05) in femoral perfusion
      pressure, with CSA blood levels in the femoral vein averaging 40 +/- 16 and 126
      +/- 50 nmol/l, respectively, at the end of the injections. Infusions of 10 and 20
      mg CSA caused significant increases in femoral perfusion pressure averaging of 8
      +/- 3 mm Hg (95% CI, 1-14; p < 0.05) and 20 +/- 4 mm Hg (95% CI, 11-29; p < 0.05)
      in femoral perfusion pressure. CSA blood levels at the end of injections averaged
      271 +/- 99 and 431 +/- 146 nmol/l, respectively, in the femoral vein. Blockade of
      alpha-adrenergic receptors with phentolamine and surgical lumbar sympathectomy
      decreased significantly the CSA vasoconstrictive effect in peripheral arterial
      vessels, with increases in perfusion pressure averaging 29 +/- 5 mm Hg before and
      14 +/- 3 mm Hg after phentolamine (p < 0.05) and 30 +/- 2 mm Hg before and 8 +/-
      2 mm Hg after sympathectomy (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356655
TI  - A study on the ecological habit of Armigeres subalbatus in Dawa area of the
      Mengshan Mountain in Shandong Province.
AB  - Armigeres subalbatus (A.s.) was reported in Shandong Province for the first time
      in 1965 and found in five counties of south Shandong including Pingyi, Linyi etc.
      in 1986. In Dawa area of the Mengshan mountain A.s. alults could be found in the
      first ten days of May, which increased in number in July, and become the dominant
      species in mosquito colonies in Aug. and Sept., then decreased gradually in
      number in Oct. and disappeared in Nov. There were two peaks of activity and blood
      sucking behavior during the 24 hours of a day, one at dusk and the other at dawn.
      When the temperature dropped to 16 degrees C and below in the last ten days of
      Oct., the wigglers began their diapause period. The survival ratio reached 90.5%
      after 12 h freezing at -5 degrees C and none survived after 60 hours freezing.
      When the temperature rose to 17 degrees C and above the over-winterting larvae
      developed into adults, which could suck blood only at the temperature above 17.5
      degrees C.

PMID- 1356654
TI  - Mechanisms of alpha 1-adrenergic vascular desensitization in conscious dogs.
AB  - To investigate the mechanisms of alpha 1-adrenergic vascular desensitization,
      osmotic minipumps containing either saline (n = 9) or amidephrine mesylate (AMD)
      (n = 9), a selective alpha 1-adrenergic receptor agonist, were implanted
      subcutaneously in dogs with chronically implanted arterial and right atrial
      pressure catheters and aortic flow probes. After chronic alpha 1-adrenergic
      receptor stimulation, significant physiological desensitization to acute AMD
      challenges was observed, i.e., pressor and vasoconstrictor responses to the alpha
      1-adrenergic agonist were significantly depressed (p < 0.01) compared with
      responses in the same dogs studied in the conscious state before pump
      implantation. However, physiological desensitization to acute challenges of the
      neurotransmitter norepinephrine (NE) (0.1 micrograms/kg per minute) in the
      presence of beta-adrenergic receptor blockade was not observed for either mean
      arterial pressure (MAP) (30 +/- 7 versus 28 +/- 5 mm Hg) or total peripheral
      resistance (TPR) (29.8 +/- 4.9 versus 28.9 +/- 7.3 mm Hg/l per minute). In the
      presence of beta-adrenergic receptor plus ganglionic blockade after AMD pump
      implantation, physiological desensitization to NE was unmasked since the control
      responses to NE (0.1 micrograms/kg per minute) before the AMD pumps were now
      greater (p < 0.01) than after chronic AMD administration for both MAP (66 +/- 5
      versus 32 +/- 2 mm Hg) and TPR (42.6 +/- 10.3 versus 23.9 +/- 4.4 mm Hg/l per
      minute). In the presence of beta-adrenergic receptor, ganglionic, plus NE-uptake
      blockade after AMD pump implantation, desensitization was even more apparent,
      since NE (0.1 micrograms/kg per minute) induced even greater differences in MAP
      (33 +/- 5 versus 109 +/- 6 mm Hg) and TPR (28.1 +/- 1.8 versus 111.8 +/- 14.7 mm
      Hg/l per minute). The maximal force of contraction induced by NE in the presence
      or absence of endothelium was significantly decreased (p < 0.05) in vitro in
      mesenteric artery rings from AMD pump dogs compared with saline control dogs.
      Furthermore, alpha 1-adrenergic receptor density, as determined by [3H]prazosin
      binding in membrane preparations from vessels in the mesentery, was decreased
      (8.2 +/- 1.0 versus 18.4 +/- 1.4 fmol/mg protein, p < 0.001) without any change
      in Kd in the AMD pump dogs compared with the saline pump dogs.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1356656
TI  - Role of alpha 2-adrenoceptors in normal and atherosclerotic human coronary
      circulation.
AB  - BACKGROUND: Experimental studies on the effects of alpha 2-adrenoceptors on
      regional coronary blood flow in normal and ischemic myocardium are highly
      controversial. A beneficial effect on regional ischemic myocardium has been
      demonstrated in different animal preparations with either alpha 2-adrenoceptor
      blockade or stimulation. Animal studies also demonstrated that postsynaptic alpha
      2-adrenoceptors mediate vasoconstriction in coronary and femoral vascular beds.
      The aims of the study were 1) to investigate the effects of regional alpha 2
      adrenoceptor stimulation on regional coronary blood flow in subjects with
      angiographically normal coronary arteries, 2) to assess the effect of alpha 2
      adrenoceptor blockade on coronary circulation in control subjects, and 3) to
      examine the influence of atherosclerosis on coronary blood flow response to alpha
      2-adrenoceptor blockade. METHODS AND RESULTS: The effect of regional
      administration of BHT 933 (a selective alpha 2-adrenoceptor agonist) was studied
      in eight subjects with angiographically normal coronary arteries. The coronary
      blood flow velocity was measured using a subselective intracoronary 3F Doppler
      catheter and coronary diameter by quantitative coronary angiography. BHT 933
      induced a reduction in coronary artery diameter from 2.5 +/- 0.6 mm to 1.8 +/-
      0.4 mm (p less than 0.05) as well as in coronary blood flow velocity (from 6.4 +/
      0.9 cm/sec to 4.6 +/- 1.9 cm/sec, p less than 0.01). In some subjects, ST
      segment abnormalities occurred. In patients with angiographically normal coronary
      arteries (n = 6), the regional infusion of a selective alpha 2-adrenoceptor
      blocking agent after beta-blockade did not change coronary diameter or coronary
      blood flow velocity. In contrast, in patients with significant coronary stenoses
      (n = 6), regional infusion of an alpha 2-adrenoceptor blocking agent reduced
      regional coronary artery diameter (from 2.3 +/- 0.5 mm to 2.1 +/- 0.6 mm, p less
      than 0.01) as well as coronary blood flow velocity (from 5.8 +/- 0.8 cm/sec to
      3.7 +/- 0.6 cm/sec, p less than 0.05); in addition, alpha 2-adrenoceptor blockade
      significantly increased coronary sinus plasma norepinephrine levels (from 300 +/-
      144 pg/ml to 429 +/- 207 pg/ml, p less than 0.01). CONCLUSIONS: The selective in
      vivo stimulation of alpha 2-adrenoceptors produces a reduction in coronary blood
      flow and diameter in humans with angiographically normal coronary arteries. alpha
      2-Adrenergic blockade does not change coronary blood flow in subjects with
      angiographically normal coronary arteries (suggesting no resting alpha 2
      adrenergic vasoconstrictor tone), whereas in patients with coronary artery
      stenosis, regional coronary blood flow decreases after alpha 2-receptor blockade.
      Finally, our data also suggest that alpha 2-adrenoceptors participate in the
      modulation of sympathetic neuronal norepinephrine release in the human heart.

PMID- 1356648
TI  - Active cell death in hormone-dependent tissues.
AB  - Active cell death (ACD) in hormone-dependent tissues such as the prostate and
      mammary gland is readily induced by hormone ablation and by treatment with anti
      androgens or anti-estrogens, calcium channel agonists and TGF beta. These agents
      induce a variety of genes within the hormone-dependent epithelial cells including
      TRPM-2, transglutaminase, poly(ADP-ribose) polymerase, Hsp27 and several other
      unidentified genes. Not all epithelial cells in the glands are equally sensitive
      to the induction of ACD. In the prostate, the secretory epithelial cells that are
      sensitive to hormone ablation are localized in the distal region of the prostatic
      ducts, and are in direct contact with the neighboring stroma. In contrast, the
      epithelial cells in the proximal regions of the ducts are more resistant to
      hormone ablation, probably because the permissive effects of the stroma are
      attenuated by the presence of the basal epithelial cells, which are intercalated
      between the epithelium and stroma. The underlying biology of ACD in prostate and
      mammary glands, and its relevance to hormone resistance, is discussed in this
      review.

PMID- 1356657
TI  - [Influence of moxibustion on TXA2 and PGI2 in plasma of rat infected epidemic
      hemorrhagic fever virus (EHFV)].
AB  - In this paper, the model of rat infected EHFV was made and the influence of
      moxibustion on TXA2 and PGI2 in its plasma was observed. The results show that
      the content of TXA2 increased and PGI2 decreased in rat significantly after the
      abdominal inoculation of EHFV, and the content of TXA2 decreased and PGI2
      increased markedly in rat infected EHFV to normal level after treatment with
      moxibustion, suggesting that the regulative function of moxibustion on TXA2 and
      PGI2 is one of its nerve-endocrine-immune regulations to the body, and there is
      an important significance. This study provides an important reference for
      mechanism exploration of moxibustion preventing and treating EHF.

PMID- 1356659
TI  - Cortical AMPA receptors: age-dependent regulation by cellular depolarization and
      agonist stimulation.
AB  - We have recently shown that a high-affinity AMPA receptor labelled with the
      antagonist [3H]CNQX can be regulated in a 'living' cortical slice preparation by
      agonist stimulation or changes in electrical activity (Lanius, R.A. and Shaw, C.
      (1992) Anat. Rec., in press). Based on a study of GABAA receptors (Shaw, C. and
      Scarth, B.A. (1992) Mol. Brain Res., in press), which showed age-dependent
      changes in regulation, we have now investigated the regulation of high-affinity
      AMPA receptors in neocortex at different stages in postnatal development. The
      results show that regulation by agonist stimulation and increases in bioelectric
      activity are age-dependent in amount and, in the latter case, in direction.
      Agonist stimulation using quisqualate resulted in a significant receptor down
      regulation of approximately 7% at ages less than 20 days postnatal; in adult rats
      quisqualate led to a significant 23% decrease. Changes in bioelectric activity
      induced by a combination of veratridine and glutamate showed a significant
      increase in AMPA receptor number of 16% at ages less than 20 days, whereas such
      treatment resulted in a significant 18% decrease in adult rats. The present data
      reveal a near mirror-image to the effects of veratridine and glutamate and
      agonist on GABAA receptors in the same preparation, but with a temporal mismatch
      in the amount and direction of regulation. We speculate that the age-dependent
      differences in direction of regulation for the receptor populations which serve
      key excitatory and inhibitory functions in cortex may provide a molecular basis
      for the gradual decline of neuronal plasticity during the critical period.

PMID- 1356658
TI  - Early postnatal changes in presynaptic potassium sensitivity.
AB  - Amplitude histograms of miniature endplate potentials (MEPPs) and the overall
      frequency of skew-MEPPs and bell-MEPPs were examined in 5 and 15 mM potassium
      solutions at postnatal day (PD) 3, PD 10 and PD 27 neuromuscular junctions.
      Temporal non-uniformities in spontaneous release produced clusters of bell-MEPPs
      at PD 0-PD 3 junctions. PD 3 nerve terminals that preferentially released skew
      MEPPs (5 mM potassium) were significantly (P less than 0.01) less sensitive to
      elevations in potassium than more mature (PD 10) junctions that preferentially
      released bell-MEPPs. Increases in the potassium concentration at PD 3 junctions
      increased the frequency of bell-MEPPs and altered the MEPP amplitude distribution
      profile by significantly (P less than 0.01) reducing the percentage of skew
      MEPPs. Although the potassium sensitivity of PD 10 and PD 27 preparations were as
      expected for adult preparations, there was an increase in overall MEPP frequency
      in 5 mM potassium between PD 10 and PD 27. These results suggest that early
      postnatal increases in the number of presynaptic calcium channels establish adult
      levels of depolarization sensitivity and promote the preferential spontaneous
      release of bell-MEPPs. Since these changes occur during an early period of
      synapse elimination, they may play a critical role in synapse stabilization.

PMID- 1356661
TI  - Detection of a T/C polymorphism in the porphobilinogen deaminase gene by
      polymerase chain reaction amplification of specific alleles.

PMID- 1356660
TI  - An immunohistochemical study of regenerating newt retinas.
AB  - Light-microscopical examination was carried out to investigate the emergence and
      development of several classes of immunoreactive cells in regenerating retinas of
      the adult newt (Triturus pyrrhogaster) after total retinal ablation.
      Immunoreactive proliferating cell nuclear antigen (ir-PCNA, a marker for
      replicating cells) was present in nuclei of all neuroblasts in the early mono
      layered to several-layered stages (15-20 days after retinal ablation; days 15
      20), but was lost progressively in an intermediate-to-central/peripheral order as
      cells and layers increased (days 20-25). Cells, which had lost ir-PCNA, began to
      separate to form the outer nuclear, inner nuclear and ganglion cell layers around
      days 25-30 (the cell separation stage). Finally, the location of ir-PCNA was
      restricted to a band of neuroblast cells at the retinal margin (days 30-35) as
      seen in intact adult retinas. Visinin-immunoreactive (ir) cells, mainly destined
      to be cones, appeared first singly or as clusters at the most distal layer in the
      intermediate region of retinas multi-layered with PCNA-ir neuroblasts, which was
      followed by appearance of opsin-ir rod outer segments and tyrosine hydroxylase-ir
      amacrine cells around the cell separation stage. Shortly later, cells
      respectively immunoreactive to glutamic acid decarboxylase, neuropeptide Y,
      serotonin, glucagon, glutamine synthetase, glial fibrillary acidic protein,
      substance P and protein kinase C were found to emerge also in an intermediate-to
      central/peripheral sequence. Some of the glucagon-ir cells appeared to be of an
      interplexiform type.

PMID- 1356662
TI  - A simple, sensitive technique for classification of apolipoprotein(a) isoforms by
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis.
AB  - Lipoprotein(a) (Lp(a)) is a lipoprotein containing a unique glycoprotein,
      apolipoprotein(a) (apo(a)), which shows considerable heterogeneity of apparent
      molecular mass on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS
      PAGE). A unifying classification of isoform has been lacking. A simple sensitive
      procedure for classifying apo(a) isoforms was developed in which the relative
      mobility of apo(a) on SDS-PAGE was related to that of apolipoprotein (apo) B-100
      (Rf vs B). After Western blotting apo(a) bands were visualised by a sensitive
      double antibody technique employing commercial polyclonal antibodies (sheep
      antihuman Lp(a) antibody, alkaline phosphatase-linked donkey antisheep antibody).
      The technique was sensitive (lower limit of detection 0.02 micrograms apo(a)) and
      had good reproducibility (coefficient of variation 0.9-6.4%). Ten isoform
      mobilities are described (less than 0.35, 0.40, 0.50, 0.60, 0.70, 0.80, 1.0,
      1.10, greater than 1.15). Individuals may have single or double band phenotypes.
      This classification is compatible with those previously described and the method
      is suitable for many laboratories, as it employs standard equipment and
      commercially available materials.

PMID- 1356663
TI  - Characterization of the carbohydrate moiety of human gamma-glutamyltransferases
      using lectin-blotting and glycosidase treatment.
AB  - The presence of both N- and O-linked carbohydrate was demonstrated on gamma
      glutamyltransferase (GT) from human liver and kidney. The N-linked carbohydrate
      constituted 25-30% of the total molecular mass of the enzymes. O-Glycosylation
      was detected on both subunits of the liver enzyme, but only on the small subunit
      of the kidney enzyme. Lectin blot analysis indicated that the glycan chains were
      of the complex type for both the liver and the kidney GT and lectin blotting may
      to some extent distinguish the two enzymes.

PMID- 1356664
TI  - HLA class II gene polymorphism contributes little to Hashimoto's thyroiditis.
AB  - Previous studies of HLA and Hashimoto's thyroiditis have shown weak associations
      between the disease and various HLA-DR antigens. OBJECTIVE: To define better the
      contribution of HLA class II alleles to susceptibility to Hashimoto's
      thyroiditis. DESIGN AND MEASUREMENTS: Comparison of HLA-DRB, DQA and DQB
      restriction fragment length polymorphisms in patients with Hashimoto's
      thyroiditis and control subjects, and meta-analysis of this and other published
      studies. PATIENTS: Fifty Caucasian patients with Hashimoto's thyroiditis and 93
      racially-matched control subjects. RESULTS: A 4.6 kb Taq 1 DQA restriction
      fragment length polymorphism occurred in 60% of patients compared with 35.5% of
      controls, Pc < 0.025. No other restriction fragment length polymorphism was
      significantly associated with the disease. Meta-analysis of several studies
      demonstrated weak, positive associations between the disease and DR3 and DR4. An
      association with DR5 was not significant. CONCLUSIONS: DR antigens are unlikely
      to determine disease susceptibility directly. These findings indicate that any
      contribution of HLA genes to inherited susceptibility to Hashimoto's thyroiditis
      is small and requires confirmation in family studies.

PMID- 1356665
TI  - A case of multiple endocrine neoplasia: hyperparathyroidism, insulinoma, GRF-oma,
      hypercalcitoninaemia and intractable peptic ulceration.
AB  - A 42-year-old woman with a family history of multiple endocrine neoplasia type 1
      (MEN 1) presented with symptomatic hypoglycaemia and peptic ulceration.
      Investigation revealed an insulinoma, hyperparathyroidism, hypercalcitoninaemia
      with a positive pentagastrin stimulation test, acromegaly due to a GRF-oma,
      hyperprolactinaemia and normal serum gastrin levels. Five pancreatic tumours were
      removed at laparotomy and immunostaining was positive for insulin, calcitonin,
      somatostatin and glucagon. Post-operatively she developed elevated serum gastrin
      levels and gross peptic ulceration, despite H2-blockers, and died of gastro
      intestinal haemorrhage suggesting that removal of the somatostatinoma may have
      allowed increased gastrin secretion from a gastrinoma. This case emphasizes the
      importance of measuring a wide variety of tumour marker peptides in MEN 1 and
      suggests that caution is required in interpretation of the pentagastrin
      stimulation test in such cases. Patients with MEN 1 and known peptic ulceration
      may require perioperative omeprazole treatment even if serum gastrin levels are
      normal.

PMID- 1356666
TI  - Effects of alpha 1-receptor blockade on the hemodynamic responses to exercise in
      young hypertensives.
AB  - The purpose of this study was to determine if alpha 1-adrenergic receptor
      blockade alters the hemodynamic response to exercise in young (less than 25 yr)
      male borderline hypertensives differently than in young normotensives. Five
      hypertensive (HTN, MAP greater than 105 mmHg) and 7 normotensive (NTN, MAP less
      than 95 mmHg) college-age males underwent two 30 min bouts of cycle ergometry
      exercise at 50% VO2pk in a warm (25 degrees C, 50% rh) environment; one following
      alpha 1-receptor blockade with prazosin (PRAZ) and the other following placebo
      administration (PLAC). During resting PLAC and compared to NTN, HTN exhibited an
      elevated cardiac index (CI, p = .002), similar HR and elevated total peripheral
      resistance index (TPRI, p = .015). During resting PRAZ, CI and TPRI were similar
      but HR was higher (p = .013) in HTN than NTN. While reduced during PRAZ, resting
      MAP was higher in HTN than NTN (p = .007) for both trials. With exercise and
      PLAC, CI was higher (p = .029) while HR and TPRI were similar for HTN compared to
      NTN. With PRAZ, the exercise CI, TPRI and HR responses were similar for both
      groups. Exercise MAP was blunted in both groups with PRAZ. While not differing
      significantly between groups for each treatment, MAP was stable for NTN while it
      declined after 10 min of exercise in HTN. The elevated CI seen in exercising HTN
      with PLAC was removed with PRAZ; the exercise response was otherwise unaltered by
      alpha 1-blockade. Consequently, these data suggest that young male hypertensives
      have an elevated blood pressure due to an elevated CI incompletely offset by a
      reduced TPRI. While alpha 1-blockade lowers MAP by lowering CI, the MAP response
      to exercise remains unaltered.

PMID- 1356667
TI  - Pseudohypoparathyroidism type I and Albright's hereditary osteodystrophy with a
      proximal 15q chromosomal deletion in mother and daughter.
AB  - A 33-year-old woman and her 71-year-old mother were both found to have
      pseudohypoparathyroidism type I with Albright's hereditary osteodystrophy
      associated with a cytogenetic deletion of the proximal part of one chromosome 15,
      resembling that found in Prader-Willi syndrome. As there are overlapping clinical
      features between these two syndromes a causal relationship cannot be excluded.
      However, molecular analyses with 10 probes from this region did not detect any
      uniparental disomy or deletion, features frequently found in Prader-Willi
      syndrome.

PMID- 1356668
TI  - Anti-endothelial cell antibodies in nephropathia epidemica and other viral
      diseases.
AB  - Increased capillary permeability is a central feature of the severe forms of
      haemorrhagic fever with renal syndrome (HFRS) and occurs also, though less
      frequently, in nephropathia epidemica (NE), one of the milder forms of this
      syndrome, caused by Puumala virus. We therefore searched for antiendothelial cell
      antibodies (AECA) in patients with NE and in those with other presumed or
      serologically proven acute viral illnesses. By enzyme immunoassay, using human
      umbilical vein endothelial cells (HUVEC) as the substrate, IgG class AECA were
      detected significantly more frequently in patients with NE and with influenza A
      than in Red Cross blood donors. A lesser degree of reactivity could be shown with
      a human alveolar cell carcinoma line and with human and mouse embryonic
      fibroblasts. Pretreatment of HUVEC with interferon-gamma (IFN-gamma), but not
      with IL-1 or tumour necrosis factor-alpha (TNF-alpha), increased their ability to
      bind IgG of sera from patients with NE and acute febrile illnesses. We conclude
      that, although AECA can be demonstrated in NE, they occur also in other acute
      viral illnesses and, unless cytopathic by a mechanism not shared by the AECA of
      these other illnesses, are unlikely to be casually related to the capillary leak
      in HFRS.

PMID- 1356669
TI  - Characterization of cytokine gene expression in CD4+ and CD8+ T cells after
      activation with phorbol myristate acetate and phytohaemagglutinin.
AB  - Cytokines are important mediators involved in the development of effector cells
      and in the regulation of immune responses. The gene expression of these mediators
      in T cell subset has yet to be fully elucidated. Using sensitive reverse
      transcription-polymerase chain reaction (RT-PCR), the kinetics of cytokine gene
      expression in human CD4+ and CD8+ T cells were examined. CD4+ T cells were more
      readily activated by phorbol myristate acetate (PMA) and phytohaemagglutinin
      (PHA) than CD8+ T cells in terms of the IL-2 receptor (IL-2R) mRNA expression.
      Quantitative differences in cytokine gene expression between CD4+ and CD8+ T
      cells were confirmed and higher levels of cytokine mRNAs were induced in CD4+
      than in CD8+ T cells. Early induction of IL-2 mRNA was observed in both T cell
      subsets. The demonstration of different kinetics of cytokine gene expression
      illustrates one of the examples of the complexity of immunoregulation. The
      differential response of cytokine gene expression in different T cell subsets
      should be taken into consideration when clinical studies in cytokine production
      by peripheral blood mononuclear cells are interpreted.

PMID- 1356670
TI  - Increased CD11/CD18 expression on peripheral blood leucocytes of patients with
      sarcoidosis.
AB  - Sarcoidosis is a multisystem disease of unknown etiology characterized by non
      caseating granulomata, formed mainly from macrophages surrounded by lymphocytes
      and plasma cells. Using a novel method for the preparation of blood leucocytes
      for flow cytometry, we report increased expression of LeuCAMs (CD11/CD18) on
      peripheral blood leucocytes of 11 Caucasian and 10 Afro-Caribbean patients with
      sarcoidosis compared with age-, sex- and race-matched controls. Whilst the
      percentages of the cells expressing CD11/CD18 were no different, the density,
      expressed as mean fluorescence intensity (MFI), was greater for all leucocytes in
      sarcoids than in normal individuals. The expression of intercellular adhesion
      molecule-1 (ICAM-1), a ligand for LFA-1 which is expressed on all leucocytes, was
      not significantly different from normal, whereas HLA-DR was expressed more
      intensely on sarcoid monocytes (P less than 0.01) and blood lymphocytes (P less
      than 0.005) than control cells. Our findings are consistent with leucocyte
      activation although we were unable to confirm reports of elevated tumour necrosis
      factor-alpha (TNF-alpha) in the patients' plasma using an ELISA. Increased
      expression of adhesion molecules on peripheral blood leucocytes may play a role
      in the cellular extravasation, aggregation, and granuloma formation seen in
      sarcoidosis.

PMID- 1356671
TI  - A study of serum prolactin levels in schizophrenia: comparison of males and
      females.
AB  - 1. Serum prolactin levels were measured in large cohorts of schizophrenic
      patients (67 males and 42 females) and normal subjects (78 males and 42 females).
      2. There was no significant differences between the serum prolactin levels of
      patients and controls, except in the age group 15-29 years. There were no
      significant differences between the serum prolactin levels of males and females,
      either among the patients or the control subjects. 3. The rise in serum prolactin
      levels after the commencement of neuroleptic medication in the patients was
      greater in females than in males even though the female patients received
      neuroleptics at lower doses. 4. These data indicate that serum prolactin levels
      in unmedicated males and females are similar; however, the prolactin response to
      neuroleptic medication is greater in females than in males.

PMID- 1356672
TI  - High blood pressure research council of Australia. Cardiovascular remodelling in
      hypertension: the role of the renin--angiotensin system and ACE inhibition.
      Melbourne, Australia, 10-11 April 1992.

PMID- 1356673
TI  - Human immunodeficiency virus-infected monocyte-derived macrophages express
      surface gp120 and fuse with CD4 lymphoid cells in vitro: a possible mechanism of
      T lymphocyte depletion in vivo.
AB  - Monocyte-derived macrophages (MDM) infected in vitro with a macrophage-tropic
      strain of human immunodeficiency virus (HIV) fused with uninfected, CD4
      expressing T lymphoblastoid cells, but not with a subclone of these cells lacking
      surface CD4. Infected MDM also fused with uninfected autologous and heterologous
      MDM. Recombinant soluble CD4 protein (rsCD4) (10 micrograms/ml) and full-length
      recombinant glycosylated gp120 (20 micrograms/ml) each inhibited fusion by 94
      99%; the inhibition was dose-dependent. The N-terminal portion of gp120 did not
      inhibit syncytium formation. Fusion was also inhibited by a monoclonal antibody
      to an epitope which binds gp120 (S3.5), but not by antibody to an epitope not
      involved in gp120 binding (OKT4). HIV-infected MDM specifically bound fluorescein
      conjugated rsCD4, and virus could be visualized budding from the surface of these
      cells. HIV-infected MDM express viral gp120 on their surface and fuse with CD4
      bearing cells in a fashion similar to lymphoid cells. Macrophages may contribute
      to CD4 lymphocyte depletion in vivo by this fusion mechanism.

PMID- 1356674
TI  - The onset of nephritis in the (NZB x SWR)F1 murine model for systemic lupus
      erythematosus correlates with an increase in the ratio of CD4 to CD8 T
      lymphocytes specific for the nephritogenic idiotype (IdLNF1).
AB  - An idiotypically related family of nephritogenic antibodies (IdLNF1) has been
      shown to be important in the pathogenesis of autoimmune glomerulonephritis in the
      (NZB x SWR)F1 hybrid, SNF1. Idiotype-specific T lymphocytes which modulate
      expression of antibody bearing that idiotype may be important in the pathogenesis
      of systemic lupus erythematosus (SLE). Here, IdLNF1-reactive T lymphocytes were
      not only found to be present in the NZB, SWR, and SNF1, but a significantly (P <
      or = 0.05) greater number of IdLNF1-reactive Thy 1.2+ splenic lymphocytes were
      observed as early as 12 weeks of age in the SNF1. Further, a significant shift in
      the ratio of CD4+ to CD8+ IdLNF1-reactive T lymphocytes in favor of CD4+ IdLNF1
      reactive T cells was observed at 20 to 24 weeks of age only in the SNF1. This
      shift correlated with an increase in IdLNF1+IgG, and deposition of IdLNF1 bearing
      immunoglobulin in the kidney glomeruli. These observations suggest a role for
      idiotype-specific T lymphocytes in the induction of glomerulonephritis in this
      murine model of SLE.

PMID- 1356675
TI  - Hormonal and immunological regulation of 2', 5'-oligoadenylate synthetase
      activity in human peripheral blood mononuclear cells.
AB  - A newly developed method for assaying 2', 5'-oligoadenylate (2, 5A) synthetase
      activity by polyacrylamide gel electrophoresis was applied to peripheral blood
      mononuclear cells (PBMC) from normal subjects, HIV-positive subjects, and renal
      cell carcinoma (RCC) patients. Sex differences were observed in 2, 5A synthetase
      activity of PBMC from normal young adults, males having eightfold higher
      activities of this enzyme than females. Moreover, compared to values for
      postmenopausal (PM) females receiving estrogen replacement, untreated PM females
      had higher activities. Collectively, these results suggest that estrogen
      downregulates 2, 5A synthetase activity. Activities of 2, 5A synthetase were
      investigated in two disease states associated with altered immune function. In
      one patient with AIDS-related Kaposi's sarcoma, interferon-alpha (IFN-alpha)
      therapy increased 2, 5A synthetase activity twofold. In addition, combined
      therapy with interleukin-2 (IL-2) and IFN-alpha increased 2, 5A synthetase
      activities in eight of nine patients with RCC. Therefore, in patients receiving
      immunotherapy with IL-2 and IFN-alpha, our new assay could contribute to
      evaluation of immune stimulation. In general, studies in vitro confirmed these
      observations; however, exposure of PBMC from RCC patients revealed that in vitro
      IL-2 failed to induce this enzyme activity as it did in PBMC from normal
      volunteers.

PMID- 1356677
TI  - The use of beta-blockade therapy in treatment of congestive heart failure.
AB  - If the activation of the sympathetic nervous system in chronic heart failure is
      causally related to progressive pump dysfunction, sudden death, and exercise
      intolerance, then selective blockade of the beta-adrenergic system may prove to
      be therapeutically beneficial. This report briefly reviews the evidence that
      there is systemic activation of the sympathetic nervous system in chronic heart
      failure, postulates mechanisms by which this activation might contribute to the
      morbidity and mortality of the syndrome, and hypothesizes further regarding how
      beta blockade may be beneficial in heart failure. The clinical evidence that the
      use of beta blockers is beneficial in the treatment of chronic heart failure is
      reviewed.

PMID- 1356676
TI  - Effective treatment of hypertension in patients with diabetes mellitus.
AB  - Atherosclerosis, presenting as macrovascular complications of diabetes mellitus,
      produces approximately 80% of all diabetic mortality, whether the patient has
      Type I insulin-dependent diabetes (IDDM) or Type II non-insulin dependent
      diabetes mellitus (NIDDM). Specifically, 75% of this atherosclerotic
      macrovascular mortality flows as the outcome of coronary atherosclerosis, which
      is increased approximately two-fold in men and four-fold in women with diabetes
      as compared with otherwise matched populations with entirely normal carbohydrate
      tolerance. The remaining 25% of this atherosclerotic mortality in patients with
      diabetes mellitus is the result either of accelerated cerebrovascular or of
      peripheral vascular complications of diabetes, both of which are increased four
      fold and five-fold, respectively, in patients with diabetes mellitus, regardless
      of type. Furthermore, atherosclerosis is the principal cause of hospitalizations
      for patients with diabetes mellitus. Admissions for this complication account for
      approximately 77% of total hospitalizations for diabetes owing to complications.
      Aside from mortality data alone, atherosclerosis is obviously a leading cause of
      diabetic disability, since it produces patients who are chronic cardiovascular,
      peripheral or cerebrovascular cripples, perhaps for many years before their
      ultimate demise. Small blood vessel or microvascular complications of diabetes
      mellitus, while formerly thought to be the end-stage in the unfolding of the
      diabetic process, do not appear to have the potential for mortality as do the
      atherosclerotic large blood vessel complications.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1356678
TI  - Regulation of in vitro anti-DNA antibody production by a novel disease modifying
      anti-rheumatic drug, Lobenzarit.
AB  - Lobenzarit (CCA) is a novel disease modifying anti-rheumatic drug. Although CCA
      has been shown to prevent the development of the autoimmune disorders in NZB/W F1
      mice and in MRL/l mice, the precise mechanism of its action has not yet been
      clarified. The current study examined the effect of CCA on the in vitro
      production of anti-DNA antibody, a hallmark of the autoimmune disorders. In vitro
      anti-DNA antibody production was induced from highly purified B cells of normal
      human individuals by stimulation with Staphylococcus aureus and CD4+ T cells or
      with immobilized anti-CD3 activated CD4+ T cells. CCA suppressed the production
      of anti-DNA antibody as well as IgM at pharmacologically obtainable
      concentrations (10-50 micrograms/ml). CCA did not inhibit the initial stages of B
      cell activation in either culture system, but rather suppressed the maturation of
      previously activated B cells. Although CCA suppressed IL2 production by
      immobilized anti-CD3 activated CD4+ T cells, its suppressive effects on B cells
      were not overcome by the addition of IL2 or factors generated from mitogen
      activated T cells (TF). CCA did not suppress IL6 production by immobilized anti
      CD3 activated CD4+ T cells nor that by B cells activated with SA+ IL2. These
      results indicate that CCA suppresses the production of anti-DNA antibody by
      directly inhibiting activated B cells. The data therefore suggest the possible
      efficacy of CCA in suppressing the function of activated B cells in human SLE
      patients.

PMID- 1356679
TI  - Immunological follow-up of 17 patients with rheumatoid arthritis treated in vivo
      with an anti-T CD4+ monoclonal antibody (B-F5)
AB  - Seventeen patients with steroid-refractory rheumatoid arthritis were treated with
      a monoclonal antibody: anti-T CD4/B-F5 (IgG1) for 10 days. The daily dose was 20
      mg. No severe side effects were observed and clinical improvement was seen in 15
      patients, accompanied by a steep decline in C reactive protein levels. This
      improvement persisted as long as 12 months in 3 patients. A decline in lymphocyte
      counts was observed 2 hours after infusion. CD3+, CD4+, CD8+ and B cells were
      affected. Monocyte levels also decreased, whereas NK cell levels remained
      unchanged. After 24 hours a subsequent recovery of lymphocyte cell numbers made
      it possible to return to pre-treatment levels. Residual CD4+ cells coated with
      CD4 antibody were sporadically found even if residual antibody could be detected
      in the serum. These results indicate insufficient mAb concentrations. No patients
      developed detectable anti-mouse Ig antibodies during the treatment period, but 5
      patients developed antibodies 15 to 30 days after the end of the treatment.
      Proliferative responses (mainly the response to ConA) were reduced at the end of
      the treatment. One month later the proliferative response returned to pre
      treatment levels. mAb treatment did not induce long lasting cell activation, as
      indicated by the low levels of CD25+ or DR+ cells. Soluble IL2 receptor levels
      were significantly higher before treatment, but did not change after treatment.
      Soluble CD8 and soluble CD4 molecules were also more numerous before treatment
      and this increase was correlated with clinical parameters. Of interest was the
      correlation between the variations in soluble CD8 and the Ritchie index during
      treatment. The increased levels of serum TNF alpha and IL6 were not modified by
      treatment. A randomized study now appears necessary to prove the efficacy of the
      treatment. Such a study would also provide biological data and thus help to
      define factors predictive of a response in this heterogeneous disease.

PMID- 1356681
TI  - International workshop on juvenile chronic arthritis.

PMID- 1356680
TI  - Dipeptidyl peptidase IV in patients with systemic lupus erythematosus.
AB  - The activity of dipeptidyl peptidase IV (DPP IV) was measured in the serum and
      peripheral blood mononuclear cells (MNC) of patients with systemic lupus
      erythematosus (SLE). The number of DPP IV positive (DPP IV+) lymphocytes in blood
      smears was determined cytochemically in groups of patients with active, moderate
      and inactive disease. Compared with healthy subjects, serum DPP IV activity was
      significantly decreased regardless of the level of disease activity. DPP IV
      activity in MNC was markedly decreased only in the patients with the active
      disease. Moreover, marked differences in the number of DPP IV+ lymphocytes could
      be detected between the groups of patients with the inactive and/or moderately
      active forms of the disease and those with active disease. The percentages of DPP
      IV+ lymphocytes, as well as DPP IV activity in MNC, showed significant
      correlations with the percentages of E-rosetting cells. Evaluation of DPP IV in
      SLE patients represents a new approach in the study of the pathological process
      of this disease.

PMID- 1356682
TI  - Hypersensitivity reaction to sulfasalazine: skin rash, fever, hepatitis and
      activated lymphocytes.

PMID- 1356684
TI  - Expression of adhesion molecules on circulating leucocytes in patients with
      inflammatory bowel disease.
AB  - 1. The expression of leucocyte antigens CD11/CD18 and complement receptor 1 was
      studied on the circulating leucocytes of 13 patients with inflammatory bowel
      disease and 13 age- and sex-matched healthy control subjects. 2. Monoclonal
      antibodies against CD11/CD18 and complement receptor 1 were added to leucocyte
      suspensions from patients and control subjects. Antibody binding was detected
      using a fluorescein-conjugated rabbit anti-mouse antibody and flow cytometry. The
      proportions of lymphocytes, monocytes and granulocytes expressing these molecules
      and the density of antigen expression, measured as mean fluorescence intensity,
      were determined. 3. There were no differences between patients and control
      subjects in the mean fluorescence intensity of antibody staining of surface
      molecules or in the proportion of cells expressing each molecule for any cell
      type. Analysis of subgroups of patients according to disease type, severity or
      treatment also showed no difference compared with control subjects. 4. We
      conclude that failure to identify a population of circulating leucocytes whose
      adhesion molecules or complement receptors are upregulated may arise because
      cells are only activated locally within the gut vasculature. Alternatively,
      structural changes in these molecules, rather than an increase in their number or
      the expression of other surface glycoproteins, may be more important in mediating
      adhesive interactions in inflammatory bowel disease.

PMID- 1356683
TI  - The effect of age and acetylator phenotype on the pharmacokinetics of
      sulfasalazine in patients with rheumatoid arthritis.
AB  - The pharmacokinetic disposition of sulfasalazine and its metabolites was studied
      in 8 young and 12 elderly patients with active rheumatoid arthritis. Equal
      numbers of slow and fast acetylators were included in each age group. Patients
      received enteric-coated sulfasalazine 2g daily for 21 days; specimens of serum
      and urine were collected for 96 h after administration on days 1 and 21. The
      elimination half-life of sulfasalazine was greater in the elderly patients. Many
      disposition parameters of sulfapyridine differed in slow and fast acetylators; of
      greatest significance were the increased values of steady-state serum
      concentration in the slow acetylators. There was no effect of age on any
      sulfapyridine disposition parameters. Values for the steady-state serum
      concentrations of N-acetyl-5-acetylsalicylic acid were greater in elderly than in
      young patients. The metabolism of sulfapyridine was markedly affected by
      acetylator phenotype and this was reflected in the composition of sulfapyridine
      related material in the urine. Thus, age is a determinant of the steady-state
      concentrations of salicylate moieties but acetylator phenotype plays a greater
      role in determining the serum concentration of sulfapyridine, which has greater
      therapeutic implications in rheumatology.

PMID- 1356685
TI  - [Micropolyarteritis. The modern nosographic picture and a discussion of a
      clinical case].
AB  - Having observed a patient presenting micropolyarteritis with necrotic skin
      lesions, hypertension and renal injury, the authors had the opportunity to define
      more closely a disease that only recently has been recognized as a separate
      nosological entity within the vast and as yet not fully understood field of
      arterial disorders. In addition, recent literature on the subject is critically
      reviewed.

PMID- 1356686
TI  - Development of a new investment for high-frequency induction soldering.
AB  - This study developed a new investment for induction soldering using high
      frequency induction heating. Ninety-five mass% magnesia clinker and 5 mass%
      dental stone were selected for the main constituents. The magnesia investment
      itself was scarcely affected by induction heating, so the addition of metal
      powders such as Fe, Ni, Co were investigated. Among these three powders, the
      addition of 10 mass% cobalt powder was most effective. This investment needed
      only 40 seconds of high frequency induction heating to go from room temperature
      to 900 degrees C without preheating. Thermal expansion of this investment in a
      vacuum atmosphere was 1.25% at 1000 degrees C. Dimensional changes during
      induction soldering were measured using German-silver and silver solder. When the
      new magnesia investment containing 10 mass% Co powder was used, the dimensional
      change was -0.2%. This contraction was less than when a magnesia investment
      without metal additives was used.

PMID- 1356687
TI  - The ontogeny of homeothermic regulation in post-hatching chicks: its influence on
      the development of hearing.
AB  - 1. The maturation of homeothermy in chicks from day 0 to day 30 after hatching
      (P0-P30) was studied by measuring rectal temperatures following different
      environmental exposures. 2. Body temperature regulation and an adult-like
      temperature (41.5 degrees C) develop with different time courses, being mature on
      days P4 and P23, respectively. After 1 hr at 20 degrees C, P0 chicks were 4.5-6.5
      degrees C cooler than P30 animals. 3. A temperature effect shifts frequency in
      the auditory pathway up to 0.5 octaves to lower values. Some shifts in tonotopic
      maps observed in developmental studies of frequency representation in awake
      chicks can be fully explained by this temperature effect.

PMID- 1356688
TI  - Synaptic transmission at high pressure: effects of [Ca2+]o.
AB  - 1. The effects of pressure on synaptic currents were examined in crayfish
      abdominal muscles. 2. Helium pressure (10.1 MPa) considerably decreased
      extracellularly-recorded excitatory junctional potentials associated with
      increased short-term facilitation. 3. These effects could be mimicked by a
      reduction of [Ca2+]o, and partially compensated by an increase in [Ca2+]o. 4.
      Pressure also reduced the amplitude of the extracellular nerve terminal
      potentials (ENTP) by up to 25%, and significantly increased synaptic delay in a
      [Ca2+]o-dependent manner. 5. The interaction between compression and various
      [Ca2+]o were analysed in terms of an existing model of transmitter release. The
      results were consistent with the hypothesis that high pressure decreases the
      maximal Ca2+ influx into nerve terminals. 6. The decreased ENTP and increased
      synaptic delay suggest that additional processes may be involved in pressure
      effects on synaptic transmission.

PMID- 1356689
TI  - Effects of angiotensin II and bladder condition on hydration behavior and water
      uptake in the toad, Bufo woodhousei.
AB  - 1. Water absorption response (WR) behavior and water weight gain were examined in
      hydrated toads, Bufo woodhousei, treated with angiotensin II (AII) or with a
      control Ringer's solution. The effects of urinary bladder condition (ad lib.
      bladder urine or empty bladder) were examined concurrently. 2. Toads treated with
      AII (100 micrograms/100 g body weight), spent more time in WR posture and
      absorbed more water than Ringer's-injected toads. 3. Toads with empty bladders
      maintained WR posture for longer periods of time and gained more weight than
      toads whose bladders were not emptied. 4. The effects of AII and bladder urine on
      water absorption by B. woodhousei appear to be separate and additive.

PMID- 1356690
TI  - Ontogeny of type I and type III deiodinase activities in embryonic and posthatch
      chicks: relationship with changes in plasma triiodothyronine and growth hormone
      levels.
AB  - 1. The ontogeny of type I and type III deiodinase activities was studied in
      embryonic and posthatch chicks. 2. Hepatic type I activity showed a 3-fold
      increase up to the period of pipping and hatching and decreased slowly
      thereafter. 3. Hepatic type III activity increased by 3-fold from E14 to E17 and
      decreased more than 10-fold from E17 to C0. Posthatch levels were very low. 4.
      Type I activity in the kidney decreased slowly after hatching while type III
      activity was very low over the whole period studied. 5. Developmental changes
      during the late embryonic period suggest a causal relationship between the
      increase in plasma GH and T3 levels and the decrease in hepatic type III
      activity.

PMID- 1356691
TI  - Sympathoadrenal activity during helox-cold induced hypothermia in Syrian
      hamsters.
AB  - 1. As reflected by increasing plasma concentrations of cortisol, norepinephrine,
      epinephrine and dopamine, a marked stimulation of the adrenal cortex and of the
      sympathetic nervous system occurred in Syrian hamsters during moderate
      hypothermia induced by helium-oxygen atmosphere and cold. 2. A profound
      hyperglycemia was observed during hypothermia. 3. All effects due to the helium
      oxygen atmosphere and cold exposure (helox-cold) disappeared almost completely
      after rewarming. 4. The results corroborate the hypothesis of an involvement of
      the adrenal cortex combined with the sympathetic nervous system in the control of
      acute induced heat production.

PMID- 1356692
TI  - Secretory oedema in diabetic submandibular glands during parasympathetic nerve
      stimulation: relationship to microvascular abnormalities in streptozotocin
      treated rats.
AB  - 1. Submandibular secretion during parasympathetic stimulation (5 Hz) was examined
      in streptozotocin-diabetic and age-matched control rats. 2. At 3 weeks, but not 3
      and 6 months, flow rate was initially greater than in controls, but it declined
      rapidly after 30 min. 3. The reduction in flow rate was associated with oedema of
      the gland. 4. At 3 months, graded stimulation revealed a tendency to oedema at
      frequencies of 10 Hz and above. 5. Morphologically, submandibular capillary
      density was increased in diabetic rats. 6. Thus, in diabetes the submandibular
      gland appears less able to withstand continuous parasympathetic stimulation, due
      in part to an increase in tissue capillary area.

PMID- 1356693
TI  - Preparation and execution of movement: parallels between insect and mammalian
      motor systems.
AB  - 1. The organization of the motor systems underlying locomotion in insects and
      mammals is surprisingly similar. There are also parallels between the insect
      motor system and the system underlying reaching and the occulomotor system in
      primates. 2. The movements generated by all these systems are planned or prepared
      before their execution and there is a partial separation of circuits for
      preparation and execution. 3. These circuits consist of multiple descending
      pathways interconnected to form overlapping loops which work co-operatively to
      determine the motor output. Thus, both insect and mammalian motor systems can be
      treated as parallel distributed (PDP) systems. 4. This enables a comparison of
      functional levels of processing in the different systems and also provides a
      basis for modelling motor systems with attractor neural networks.

PMID- 1356694
TI  - Effects of dehydration and rehydration on the intravascular space in horses.
AB  - 1. The resistance of sub-tropical horses, and desert-dwelling horses to 72 hr
      dehydration/24 hr rehydration was investigated via changes in red cell parameters
      and plasma protein concentration. 2. Red cell count, haemoglobin and haematocrit
      increased up to 48 hr dehydration. Between 48 and 72 hr dehydration these
      parameters decreased, implying a fluid shift onto the intravascular space from
      the interstitium/hindgut. Most parameters had regained baseline values by 24 hr
      rehydration. 3. Mean cell volume, mean cell haemoglobin, mean cell haemoglobin
      concentration and total plasma protein were not significantly different between
      breeds at, or between most stages of hydration. 4. Protection of plasma volume
      during dehydration/rehydration was aided by maintaining intravascular protein
      (especially albumin) levels. Red cells were transiently dehydrated and
      overhydrated but resisted osmolysis.

PMID- 1356695
TI  - Age influences on amino acid intestinal transport.
AB  - 1. Intestinal absorption of amino acids show a decrease with aging in different
      animal species such as avians, rodents and ruminants. 2. The different intestinal
      segments show different absorptive capacities, the jejunum being the most
      absorbent. 3. Chickens show the biggest capacity for amino acid absorption close
      to hatching. 4. In rodents the third week seems to be the period of increased
      transport capacity.

PMID- 1356696
TI  - An in vitro study of short-chain fatty acid concentrations, production and
      absorption in pig (Sus scrofa) colon.
AB  - 1. Short-chain fatty acid concentration was 180 mmol/l in the proximal colon and
      decreased to 108 mmol/l in the rectum. 2. Fermentation in chymus from different
      regions of the colon, showed the pattern of end products to reflect the substrate
      and not the site of the colon. 3. Isolated mucosa from proximal and distal colon
      had electroneutral sodium absorption of 4.8 +/- 0.2 and 2.9 +/- 0.8 mueq/cm2 hr
      in bicarbonate free media, which was abolished in the absence of chloride. 4.
      Electroneutral sodium absorption was enhanced by short-chain fatty acids in the
      proximal colon and could be described by Michaelis-Menten kinetics with Km 2.0-11
      mmol/l and Jm 1.6-3.6 mueq/cm2 hr. In the distal colon the stimulation was
      smaller and propionate even inhibited sodium absorption. 5. Butyrate was absorbed
      in the proximal colon, whereas acetate and propionate, and butyrate in the distal
      colon had a flux ratio of one. 6. Amiloride (5 mmol/l) inhibited sodium
      absorption and net butyrate absorption.

PMID- 1356697
TI  - Influence of dietary sources of fat on lipid synthesis in mink (Mustela vison)
      mammary tissue.
AB  - 1. The fatty acid composition of the triglyceride fraction of mink milk sampled
      during mid-lactation (day 28 post partum) from two nursing mink was compared to
      that of plasma samples and to the fatty acid composition of the feed rations
      used. 2. Chemical analysis of the triglyceride composition of mink milk
      demonstrated only minute concentrations of fatty acids with a chain length below
      C14. 3. The saturated C16:0- and C18:0-unit fatty acids in mink milk made up for
      24-40% of the total amount of fatty acids extracted, the remainder being
      represented by mono and polyunsaturated long-chain (C16-C24) fatty acids. 4.
      Preliminary in vitro experiments proved the incorporation of 14C-labelled
      glucose, acetate or palmitate into triacylglycerols in cultures of mink mammary
      tissue to be linear for at least 2 hr. 5. The in vitro capacity for de novo fatty
      acid synthesis in mink mammary tissue using 14C-labelled glucose or acetate was
      low, i.e. ranging from 0.096-0.109 nmol/g (fresh tissue)/min, and amounted to
      only about 5% of that obtained in the case of [14C]palmitic acid incubation. 6.
      Following 14C-labelled acetic or palmitic acid incubation of mink mammary tissue
      neither desaturation nor chain elongation was observed. 7. In response to long
      term feeding on rations with two different sources of animal fat (F = fish oil or
      L = lard) the influence of compositional changes in dietary neutral lipids on the
      fatty acid composition of the lipids of mink milk is discussed.

PMID- 1356698
TI  - The effects of paralysis on skeletal development in the chick embryo.

PMID- 1356699
TI  - Similarities and differences between rabbit and human platelet characteristics
      and functions.

PMID- 1356700
TI  - Effects of arterial insufficiency on glucose uptake by fast and slow rat skeletal
      muscles.
AB  - 1. Muscle wet weight and glucose uptake were measured in female Wistar rats 7 and
      14 days after unilateral ligation and section of the artery. 2. Following the
      induction of arterial insufficiency, muscle wet weight decreased significantly in
      the extensor digitorum longus (EDL), but not in the soleus muscle (Sol). 3.
      Muscle glucose uptake per wet weight increased significantly in EDL after
      arterial insufficiency, but not in Sol. 4. It is suggested that arterial
      insufficiency influences the metabolic control of fast muscle via anoxia as a
      main etiologic factor.

PMID- 1356701
TI  - Circulating vasotocin in the snake Bothrops jararaca.
AB  - 1. There is biochemical and pharmacological evidence to suggest the presence of
      vasotocin in the blood and plasma of the snake Bothrops jararaca (Bj). 2. XE-64
      extracts from Bj blood showed antidiuretic and hypotensive activities in rats and
      a contractile effect on rat isolated uterus, which was totally dialysable and
      inhibited by thioglycollate. 3. Extracts from Bj whole plasma presented an
      antidiuretic activity which was only partially dialysable. 4. The plasma extracts
      also showed oxytocic properties. 5. When EDTA and Sep-Pak C18 extraction were
      used, a better recovery and characterization of vasotocin by HPLC was obtained.
      6. These results indicate the occurrence of free and bound circulating vasotocin
      in Bj, in an equilibrium dependent of its enzymatic hydrolysis.

PMID- 1356702
TI  - Adrenocortical responsiveness to immobilization stress in spotted hyenas (Crocuta
      crocuta).
AB  - 1. The adrenocortical responsiveness to an induced stressor was monitored in free
      living spotted hyenas belonging to a number of social and reproductive
      categories. 2. No significant differences between sexes, or changes in mean
      cortisol concentrations during serial sampling within the sexes, could be
      demonstrated. 3. The extreme individual variance in temporal cortisol profiles
      recorded in this study is inexplicable, as it was not related to differences in
      immobilization procedure, sex, age, reproductive or social category. 4. Females,
      which are the dominant sex in this species, generally showed larger percentage
      increases in cortisol concentrations during serial sampling. 5. Significant
      correlations between initial cortisol concentrations, as well as cortisol
      responsiveness and androgen concentrations, in a number of social and
      reproductive categories, suggest that these categories do not provide sufficient
      resolution for the identification of specific dominance-related trends.

PMID- 1356703
TI  - Dye-coupling among frog (Rana catesbeiana) taste disk cells.
AB  - 1. Dye-coupling among taste disk cells in the bullfrog fungiform papillae was
      examined histologically by injecting a fluorescent dye (Lucifer yellow) into the
      cell, and the effects of the dye-coupling on depolarizing responses induced by
      taste stimuli were studied electrophysiologically. 2. With dye injection into a
      taste cell, dye-coupling was found between taste cells (23%) or between taste
      cell and supporting cell (28%). With dye injection into a supporting cell, dye
      coupling was found between supporting cells (34%) or between supporting cell and
      taste cell (27%). 3. Depolarizing responses recorded from either a taste cell or
      a supporting cell to stimulation with 0.5 M NaCl or 10 mM quinine-HCl were the
      same in amplitude whether the dye-coupling to another cell was present or not. On
      the other hand, depolarizing responses recorded from a taste cell for 0.5 mM
      acetic acid became significantly larger when dye-coupled to a supporting cell. 4.
      It is concluded that gustatory transduction for acid stimuli is influenced by
      supporting cells coupled to taste cells.

PMID- 1356704
TI  - The biosynthesis of polyunsaturated fatty acids by rat sertoli cells.
AB  - 1. The biosynthesis of polyunsaturated fatty acids (PUFA) of the n-6 and n-3
      series was investigated in cultured Sertoli cells. 18:2n-6, 18:3n-6, 20:2n-6,
      18:3n-3 and 20:3n-3 were added individually at a concentration of 20 mumol to
      culture media. 2. Maximum incorporation of 20- and 22-carbon PUFA into membrane
      lipids was observed after 72 hr of incubation with all the exogenous substrates
      used. 3. As reported in other cell systems, the delta 6 desaturation was the
      first rate-limiting step; the major factor regulating this activity was the
      concentration of linoleic acid or alpha-linolenic acid in the medium. 4. Our data
      show that the delta 5-desaturation represents a second regulatory step in PUFA
      biosynthesis. 5. The sum of n-6 and n-3 PUFA of the 22 carbon chain length
      constantly represented between 11 and 12% of total fatty acids, regardless of the
      exogenous substrate used. 6. Our kinetic studies of the incorporation of PUFA of
      the n-6 and n-3 series did not permit detection of a delta 8 desaturase activity.

PMID- 1356705
TI  - 2nd Japan-Nordic PACS Symposium. Tampere, Finland, June 9-11, 1991.

PMID- 1356706
TI  - User requirements and standards for PACS. 2nd Japan-Nordic PACS Symposium.
AB  - PACS has been regarded as a system which will bring a new era to image handling,
      radiology departments and its services to other departments of the hospital.
      However, many recently held international conferences indicate that a worldwide
      consensus on 'what is PACS, why is PACS needed and who is PACS for' has not been
      established. Although the actual PACS implementation will vary among the
      countries and according to each situation, a worldwide consensus of PACS should
      be possible. This would help those involved to speed up the implementation of
      PACS. It is suggested that this consensus needs to be developed by convergence of
      three points of view; the availability, maturity and cost of the technologies on
      which PACS is built, the user requirements for PACS and standardization in PACS.
      These themes were the topics of the 2nd Japan-Nordic PACS Symposium which was
      arranged in Tampere, Finland, June 9-11th 1991. A summary of the papers and
      discussions of the symposium is produced in this paper.

PMID- 1356707
TI  - Do the benefits outweigh the costs of PACS? The results of an International
      Workshop on Technology Assessment of PACS.
AB  - On May 26-27, 1991, an International Workshop on the Technology Assessment of
      PACS was held at Enkhuizen, The Netherlands. During this workshop 35 experts in
      the field, from 13 different countries, discussed amongst others the required
      functionality of PACS, diagnostic aspects and the quality of care and
      organizational aspects. The key question was whether, when and how PACS is
      feasible, both from a financial and a clinical point of view. Data which were
      collected with the aid of the software tool CAPACITY formed the starting point of
      this meeting. This paper gives an outline of the discussions during this
      workshop. The main conclusion is that more clinical research is needed, to get a
      better insight into the costs and the clinical benefits of PACS. Because of the
      high costs of the PACS technology, international cooperation in this field is
      requested. It is recommended that the CAPACITY project, which is set up to
      stimulate the international dialogue and data exchange on PACS, is continued.

PMID- 1356708
TI  - DSM-II personality characteristics of panic disorder with agoraphobia patients in
      stable remission.
AB  - The Personality Diagnostic Questionnaire (PDQ), a self-rating scale designed to
      assess DSM-III axis II personality disorders (PD), was administered to 12 panic
      disorder with agoraphobia patients during a 6-month stable and virtually symptom
      free remission period with the aim of assessing the personality characteristics
      of these patients in the best possible approximation of the not-ill condition in
      clinical reality. The personality profile of the sample remained unchanged during
      remission and was predominated by avoidant PD traits. In a finer grain analysis,
      the stable and commonly endorsed individual PDQ items were compared with
      previously reported panic disorder and normal control subjects, which showed that
      the present sample was more like the panic patients in their tendency to see
      themselves as rather unassertive, indecisive, self-critical, and emotional
      individuals who are easily frustrated and feel rejected when criticized by
      others. These results suggest that avoidant behavioral and attitudinal patterns
      may be enduring personality characteristics of panic disorder with agoraphobia
      patients.

PMID- 1356709
TI  - Cross-reactivity with Tagetes in Arnica contact eczema.
AB  - A 69-year-old patient, with known mercury and adhesive plaster allergy, developed
      facial dermatitis within 24 h of contact with arnica (Arnica). Skin testing
      showed positive reactions to arnica and, among various other plants of the
      Compositae, also to Tagetes sp. hybr. (marigold). Cross-reactivity between
      Tagetes and arnica has not previously been described.

PMID- 1356711
TI  - [Hypoplasia of the pancreatic body and tail with chronic pancreatitis of the head
      of the pancreas].

PMID- 1356710
TI  - Tetrazepam allergy once more detected by patch test.

PMID- 1356712
TI  - [Summary of the national obstetrics and gynecology symposium on complications of
      pregnancy and functional uterine bleeding].

PMID- 1356713
TI  - [A study on virus localization and microcirculation in the liver in patients with
      epidemic hemorrhagic fever].
AB  - The findings in our clinical study was consistent with those reported by others
      that a temporary elevation of serum alanine aminotransferase activity is
      associated with epidemic hemorrhagic fever (EHF). However, the pathogenesis of
      the concomitant changes in liver function tests is still not clear. To clarify
      whether EHF virus is cytopathic or not for the liver, percutaneous liver biopsy
      was done in 19 patients with EHF within 3-12 days after the onset of symptoms.
      These liver biopsy specimens were examined with immunofluorescence assay and cell
      cultural technique, showing the presence of active viral replication in liver
      cells. Electron microscopy observation of the infected liver cells showed that
      ultrastructural distortions was accompanied by the existence of inclusion bodies
      of EHF virus in vacuoles of rough endoplasmic reticulum, endotheliocyte and
      microvilli. These findings strongly suggest that EHF virus may play a causative
      role in liver injury in patients suffering from EHF and hepatic microcirculation
      disturbance may be involved in the pathogenesis of EHF-related liver dysfunction
      as well.

PMID- 1356714
TI  - [A study on pathogenesis and therapy of hemorrhagic fever with renal syndrome].
AB  - 581 early cases of typical hemorrhagic fever with renal syndrome (HFRS) were
      dynamically studied on the clinical manifestations and laboratory findings from
      1986 to 1989. All the patients were treated with various methods. The results
      showed: (1) The manifestations of microvascular damage, proteinuria and
      thrombocytopenia can be found at the first day of the onset in 80.0%, 72.2% and
      33.3% respectively. In a word, the characteristic features of HFRS appear at the
      onset of the disease. (2) In 446 early cases the initial severity of the disease
      corresponded with the final severity at a rate of 89.2%; it indicated that the
      damage of HFRS may result from the first attack. (3) The time of the onset, peak
      and persistence of all the characteristic features were similar; it is suggested
      that the course of HFRS may be self-limited. (4) Based on the clinical
      understanding and the effective results in the 446 early cases treated with fluid
      therapy alone, we consider that the effective treatment of HFRS is early and
      reasonable fluid therapy.

PMID- 1356715
TI  - Interactions among cell signalling systems. Proceedings of symposium. Kobe,
      Japan, 23-25 April 1991.

PMID- 1356716
TI  - Ca(2+)-cyclic AMP interactions in sustained cellular responses.
AB  - As early as 1970 it was apparent that the cyclic AMP (cAMP) and Ca2+ messenger
      systems often interact to regulate cellular responses. Work over the past 20
      years has greatly expanded our knowledge of these interactions, and has shown
      that these signalling systems interact in complex ways to regulate sustained
      cellular responses such as aldosterone secretion, smooth muscle contraction and
      insulin secretion. The latter system is considered in detail because it
      illustrates several types of interactions, both positive and negative, which help
      to determine the normal response of beta-cells to physiological stimuli, and how
      abnormalities in secretory patterns can develop as a consequence of the prolonged
      stimulation of a messenger system.

PMID- 1356717
TI  - [The correlation between clozapine saliva level and clinical response as well as
      side effect in patient with schizophrenia].
AB  - It was measured for clozapine saliva level in 62 patients with schizophrenia
      taking clozapine, the study have found that therapeutic window was at the range
      from 550 ng/ml to 920 ng/ml in 34 patients with duration more than two years and
      was at the range from 400 ng/ml to 510 ng/ml in 28 patients with duration less
      than two years. Clozapine saliva concentration has positively correlated with
      improvement of though disorders and hostility & suspiciousness in 30 patients
      with duration more than two years and with improvement of activation in 12
      patients with duration less than two years and with anti-adrenergic side effect
      in 62 patients, the latter effect was significant increased when clozapine saliva
      level was more than 380 ng/ml.

PMID- 1356718
TI  - [A study on transmission of epidemic hemorrhagic fever virus through skin wounds
      among rodents in natural conditions].
AB  - 224 rodents captured from endemic areas of epidemic hemorrhagic fever (EHF) in
      Hubei province were examined for the presence of skin wounds and EHF viral
      antigens and antibodies by immunofluorescent assay (IFA) technique. It was found
      that 30.8% (69/224) of the captured rodents had skin wounds and that 24.6%
      (17/69) and 29.0% (20/69) of the wounded rodents were positive respectively to
      EHF viral antigens and antibodies, as compared with the corresponding rates of
      9.0% (14/155) and 8.4% (13/155) in rodents without skin wounds. This suggests
      that infection through skin wounds could be an important route of transmission of
      the EHF virus among rodents under natural conditions.

PMID- 1356719
TI  - [Preliminary studies on c-erbB-2 protooncogene in breast cancer].
AB  - c-erbB-2 protooncogene amplification was analyzed with Southern blot technique in
      50 breast cancer patients in an attempt to correlate the results with the
      prognosis. The median follow-up was 59 months. Amplification was found in 15/50
      (30%) of these patients including two cases of rearrangement. A highly
      statistically significant difference was found in postoperative survivals of
      patients with or without c-erbB-2 amplification (P less than 0.005). When
      patients were divided into groups by stage, nodal status, tumor size and PR
      status, the prognosis tended to become worse with c-erbB-2 amplification. It was
      demonstrated that the postoperative median survival of Stage I and II patients
      with amplification was similar to those of Stage III and IV patients without
      amplification (48 and 47.8 months). The postoperative median survival of node
      negative patients with amplification was shortened as compared to those of node
      positive ones without amplification (47.3 and 54 months). This observation
      indicates that c-erbB-2 amplification seems to be an useful independent prognosis
      indicator in breast cancer, particularly in identifying the subsets of high risk
      of recurrence in node negative or Stage I and II patients.

PMID- 1356720
TI  - Effects of dose, sex, and age on the disposition of alendronate, a potent
      antiosteolytic bisphosphonate, in rats.
AB  - Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate), an antiosteolytic
      agent, is currently under investigation in the treatment of a variety of bone
      disorders. Earlier studies from this laboratory have demonstrated that
      systemically administered drug was rapidly taken up by bone tissue or excreted by
      the kidneys. Approximately 60 to 70% of the dose was taken up by the bone, and 30
      to 40% was excreted in the urine. The purpose of this study was to determine the
      effects of dose, sex, and age on the disposition kinetics of alendronate using
      rats as an animal model. No evidence of saturation of drug uptake by the bone was
      observed in young rats when small, repetitive doses of alendronate were
      administered every 3 days for 21 days (total 35 mg/kg iv). However, less than
      proportional uptake by the bone was observed in young rats when single iv doses
      exceeded 10 mg/kg. Overall, a 500-fold increase in dose resulted in a 350-fold
      increase in drug concentration in bone. Nonlinear uptake of alendronate by bone
      was accompanied by simultaneous accumulation in noncalcified tissues at high
      doses. Less than 1% of the dose was found in noncalcified tissues at 24 hr after
      low doses (1 mg/kg iv), and 25% after high doses (30 mg/kg iv). Following iv
      administration, uptake of alendronate by the bone was lower in senescent rats
      than in young rats by a factor of 2 to 3. Bone uptake was lower in female rats
      than in male rats by about 30 to 40%, but this sex difference was only observed
      at low doses and in young rats.

PMID- 1356721
TI  - Metabolism of the leukotriene receptor antagonist 5-(2-(8-phenyloctyl)phenyl)-4,6
      dithianonanedioic acid (SK&F 102922) in the guinea pig. Rearrangement of the acyl
      glucuronide.
AB  - A primary route of inactivation of leukotrienes and their receptor antagonists
      (LTRA) is metabolism by omega oxidation. SK&F 102922 [5-(2-(8-phenyloctyl)phenyl)
      4,6-dithianonanedioic acid] is a LTRA that was designed to be resistant to omega
      oxidation. Therefore, these experiments were designed to characterize the
      metabolic fate of [14C]SK&F 102922. Following iv administration of SK&F 102922 (5
      mg/kg), 80% of injected radioactivity was excreted in bile in 1 hr. At least five
      metabolites and parent (18% of administered dose) were present in bile. One
      metabolite (M1), which accounted for less than 10% of the excreted radioactivity,
      was monohydroxylated. Three metabolites (M2, M3A, and M3B), which together
      accounted for greater than 50% of excreted radioactivity, had mass spectra
      consistent with acyl glucuronides. All three metabolites were alkali labile,
      whereas only one metabolite (M2) was susceptible to beta-glucuronidase
      hydrolysis. These data indicate that M3a and M3b are nonglycosidic isomers of M2
      that were formed by a nonenzymic reaction involving migration of the aglycone
      (SK&F 102922) from C-1 to C-2, C-3, or C-4 of glucuronic acid. The 1-O-acyl-beta
      glucuronide of SK&F 102922 (M2) exhibits pH dependent rearrangement, with half
      lives ranging from 1 to greater than 1000 hr. Therefore, acyl glucuronidation can
      account for much of the metabolic fate of SK&F 102922 and, potentially, other
      structurally related LTRAs or endogenous leukotrienes themselves.

PMID- 1356722
TI  - A physiologically based pharmacokinetic model for (-)-quinuclidinyl benzylate
      using nonlinear irreversible tissue binding parameters in rats.
AB  - The disposition characteristics of (-)-quinuclidinyl benzylate (QNB) were
      investigated in rats, and a physiologically based pharmacokinetic model was
      established using its linear and nonlinear tissue binding parameters. The steady
      state distribution volume (Vdss) and systemic clearance (CLtot) were comparable
      after iv administration of 325 ng/kg and 3.2 mg/kg, suggesting that QNB
      pharmacokinetics based on plasma concentrations is linear. However, tissue
      accumulation was observed in the heart, lung, muscle, and brain. This
      accumulation persisted for over 12 hr after the iv administration of 325 ng/kg
      [3H]QNB. Tissue binding parameters were determined after continuous infusion of
      QNB. Irreversible and nonlinear binding parameters were obtained in various
      regions of the brain and other tissues. Reversible equilibrium concentration
      ratios between tissue and plasma were determined after high-dose infusion. QNB
      concentrations in the plasma, heart, lung, muscle, and brain were predicted after
      the administration of 325 ng/kg or 3.2 mg/kg. There was reasonable agreement
      between the model predictions and the observed data.

PMID- 1356723
TI  - Lack of effect of streptogramins on hepatic drug metabolism enzymes in the rat.
AB  - Male Sprague-Dawley rats were treated with streptogramin derivatives (RP 7293, RP
      54476, RP 57669, and RP 59500) or with the macrolide troleandomycin. Liver
      cytosol and microsomes were prepared, and the in vitro transformation of several
      model substrates studied. Furthermore, total and complexed microsomal cytochrome
      P-450 levels were compared. Hepatic cytochrome P-450 metabolite complexes were
      detected 4 days after troleandomycin treatment (500 mg/kg/day po), whereas such
      effects were not observed with po RP 7293 (500 mg/kg/day, 4 days) or with iv RP
      54476 (12 mg/kg/day, 7 days), RP 57669 (6 mg/kg/day, 7 days), or RP 59500 (6 and
      18 mg/kg/day, 7 days). The administration of troleandomycin resulted in
      statistically significant increases in liver weight (+20%), microsomal protein
      (+70%), total cytochrome P-450 (+187%), and cytosolic glutathione S-transferase
      activity (+32%). The activities of aniline hydroxylase, aminopyrine N
      demethylase, and the high and low phases of 7-ethoxyresorufin O-deethylase were
      markedly decreased by 36% to 56%. In contrast, none of these hepatic parameters
      was changed significantly after administration of each streptogramin. These
      results suggest that streptogramins have not, in contrast to many commonly used
      macrolide antibiotics, had potent or specific effects on hepatic drug
      metabolizing enzymes in rats.

PMID- 1356724
TI  - Probenecid-impaired biliary excretion of acetaminophen glucuronide and sulfate in
      the rat.
AB  - Acetaminophen (APAP; 100 mg/kg iv) and probenecid (50 mg/kg bolus + 11.4 mg/hr/kg
      infusion) were administered to male Sprague-Dawley rats to examine the
      disposition of APAP, and its glucuronide (AG) and sulfate (AS) conjugates in
      plasma, bile, and urine. Probenecid significantly decreased the formation
      clearance of AG from 3.65 +/- 0.434 to 1.94 +/- 0.441 ml/min/kg and the renal
      clearance of AS from 9.32 +/- 2.26 to 3.15 +/- 1.21 ml/min/kg. The biliary
      excretion of AG was reduced approximately 3- to 4-fold by probenecid, from 6.54
      to 1.87% of the APAP dose, and the AG biliary excretion rate was decreased 4- to
      5-fold during probenecid treatment. The more extensive impairment of AG biliary
      excretion relative to AG formation suggests that probenecid may inhibit the
      hepatobiliary transport of AG. The significant reduction in the biliary excretion
      rate at early time points for AS suggests that probenecid may inhibit hepatic AS
      transport. The study results indicate that probenecid impairs AG and AS
      formation, AS renal secretion, and AG and AS biliary excretion.

PMID- 1356725
TI  - Metabolism of simultaneously administered antipyrine and theophylline in male
      BN/BiRij rats before and after induction with 3-methylcholanthrene.
AB  - In order to study the metabolic activities of different P-450 enzymes in male
      Brown Norway rats, formation rates of antipyrine (AP) metabolites and
      theophylline (TH) metabolic clearance were determined. Brown Norway rats are
      often used in studies concerning the influence of age on liver function.
      Experiments were performed after simultaneous iv administration of the two
      compounds with and without 3-methylcholanthrene (3-MC) pretreatment.
      Pharmacokinetic data of both AP and TH were significantly influenced by 3-MC
      pretreatment. Metabolic clearance of AP increased from 6.8 +/- 1.0 (mean +/- SD,
      N = 23) to 18.4 +/- 7.9 (N = 10) ml.min-1.kg-1, whereas the metabolic clearance
      of TH increased from 1.9 +/- 0.6 to 20.0 +/- 5.1 ml.min-1.kg-1. Elimination half
      life in plasma decreased from 77 +/- 10 to 33 +/- 9 min for AP and from 171 +/-
      36 to 25 +/- 7 min for TH, respectively. Urinary recovery as the metabolites 3
      hydroxymethylantipyrine, 4-hydroxyantipyrine, and norantipyrine accounted for
      approximately 36% of the administered dose in the control situation, and for
      approximately 21% after 3-MC pretreatment. 3-MC pretreatment strongly reduced the
      formation of 3-hydroxymethylantipyrine, but increased the formation rate of 4
      hydroxyantipyrine and norantipyrine. Weak correlations were found between the
      clearances of formation of the AP metabolites and the metabolic clearance (CLm)
      of TH in the control rats. This may be caused by a large contribution of
      constitutive P-450 enzymes in the formation of AP metabolites and/or the
      metabolic clearance of TH in Brown Norway rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356726
TI  - Noninvasive in vivo 13C-NMR spectroscopy in the rat to study the pharmacokinetics
      of 13C-labeled xenobiotics.
AB  - Noninvasive NMR methodology has been developed to enable monitoring of 13C
      labeled xenobiotics in the rat in vivo. 2,2-Dichloro-1-(2-chlorophenyl)-1-(4
      chlorophenyl)-[3-13C]-propane can be detected in the liver of intact rats by in
      vivo 13C surface coil NMR spectroscopy after ip administration of the compound.
      The experiments were performed at 1.9 and 9.4 Tesla. The intrahepatic changes of
      the signal intensity of the labeled compound were followed as a function of time.
      In the days following administration, the concentration decreased and dropped to
      values below the detection limit after 12 days. The study demonstrates the
      feasibility of studies on pharmacokinetics of 13C-labeled compounds in the rat
      using noninvasive, in vivo surface coil NMR spectroscopy in animals. The
      sensitivity allows the detection of a single dose of the drug of 200 mg/kg, but
      can be improved.

PMID- 1356727
TI  - Effects of pregnancy and ethanol treatment on the metabolism of 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone by hamster liver and lung
      microsomes.
AB  - The tobacco-specific N-nitrosamino 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) is a potent carcinogen in adult Syrian golden hamsters and causes a high
      incidence of tumors in the offspring of hamsters after in utero exposure. We have
      investigated how pregnancy and/or ethanol treatment modulates the microsomal
      metabolism of NNK. Pregnancy decreased the alpha-carbon hydroxylation
      (activation) of NNK, whereas it increased both the pyridine N-oxidation and
      carbonyl reduction of NNK in liver microsomes, but not in the lung. Ethanol
      treatment of nonpregnant hamsters induced both the hepatic microsomal alpha
      carbon hydroxylation and pyridine N-oxidation of NNK, but it increased only the
      formation of NNAL, the N-nitroso alcohol NNAL, in the lung. Ethanol-consuming
      pregnant hamsters showed no changes in the hepatic or pulmonary metabolism of
      NNK. In contrast, fetal hamsters exposed in utero to ethanol showed a general
      increase in the rate of metabolism of NNK. Immunoblot analyses demonstrated a
      reduction in the P-450IIE1 and total P450IIB1/IIB2 protein levels in the liver of
      pregnant hamsters, whereas a moderate increase of P-450IIB1 was observed in the
      lung. Moreover, ethanol treatment increased the amount of immunodetectable P
      450IIE1 and total P-450IIB1/IIB2 in the liver of nonpregnant hamsters, but only
      the hepatic P-450IIE1 was induced by ethanol in pregnant hamsters. The P-450IIB1
      protein levels were not affected by ethanol treatment in the lung of nonpregnant,
      pregnant, or fetal hamsters. In contrast, the fetal hepatic P-450IIE1 and P
      450IIB1/IIB2 protein levels were increased by transplacental ethanol
      exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356728
TI  - Dominant role of cytochrome P-450 2E1 in human hepatic microsomal oxidation of
      the CFC-substitute 1,1,1,2-tetrafluoroethane.
AB  - The chlorofluorocarbon substitute 1,1,1,2-tetrafluoroethane (HFC-134a) is subject
      to metabolism by cytochrome P-450 in hepatic microsomes from rat, rabbit, and
      human. In rat and rabbit, the P-450 form 2E1 is a predominant low-KM, high-rate
      catalyst of HFC-134a biotransformation and is prominently involved in the
      metabolism of other tetrahaloalkanes of greater toxicity than HFC-134a [e.g. 1,2
      dichloro-1,1-difluoroethane (HCFC-132b)]. In this study, we determined that the
      human ortholog of P-450 2E1 plays a role of similar importance in the metabolism
      of HFC-134a. In human hepatic microsomes from 12 individuals, preparations from
      subjects with relatively high P-450 2E1 levels were shown to metabolize HFC-134a
      at rates 5- to 10-fold greater than microsomes of individuals with lower levels
      of this enzyme; the increased rate of metabolism of HFC-134a was specifically
      linked to increased expression of P-450 2E1. The primary evidence for this
      conclusion is drawn from studies using mechanism-based inactivation of P-450 2E1
      by diethyldithiocarbamate, competitive inhibition of HFC-134a oxidation by p
      nitrophenol (a high-affinity substrate for P-450 2E1), strong positive
      correlation of rates of HFC-134a defluorination with p-nitrophenol hydroxylation
      in the study population, and correlation of P-450 2E1 levels with rates of
      halocarbon oxidation. Thus, our findings support the conclusion that human
      metabolism of HFC-134a is qualitatively similar to that of the species (rat and
      rabbit) used for toxicological assessment of this halocarbon.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1356729
TI  - Tissue distribution and lung localization of [14C]azelastine in guinea pigs.
AB  - Tissue distribution was performed in male guinea pigs that received a single oral
      dose of 1 mg/kg [14C]azelastine. Determination of 14C concentrations by liquid
      scintillation counting in 16 tissues and by whole-body autoradiography showed
      preferential uptake of the radioactivity by the lung. The liver had a higher and
      all other tissues had lower concentrations of 14C than the lung. The lowest 14C
      concentrations were in the eyes and brain. Light microscopy autoradiography of
      lung and trachea sections indicated localization of 14C, possibly in alveolar
      macrophages. The radioactivity cleared completely from lung tissue, as well as
      from other tissues within 48 hr.

PMID- 1356730
TI  - Pharmacokinetics of azelastine and its active metabolite, desmethylazelastine, in
      guinea pigs.
AB  - Pharmacokinetics of azelastine (AZ) and its major active metabolite
      desmethylazelastine (DAZ) after iv or po administration of 1 mg/kg [14C]AZ
      hydrochloride or unlabeled AZ hydrochloride were studied in guinea pigs. Total
      14C radioactivity concentrations in blood, plasma, lung, urine, and feces were
      determined by liquid scintillation counting. AZ and DAZ concentrations in the
      plasma and lung samples were determined by HPLC methods. For pharmacokinetic
      modeling, the mean concentrations of AZ and DAZ in plasma were converted to those
      in blood. Following the iv or po dose, AZ blood concentrations declined
      biexponentially with the distribution and elimination phases. The open two- and
      one-compartment models for AZ and DAZ concentrations in blood, respectively, and
      the open one-compartment model for the two compounds in lung tissue describe the
      experimental data reasonably well. The apparent volume of distribution of AZ
      suggested that the drug was widely distributed in the body. The mean lung/blood
      concentration ratios, which varied from 14.2 to 20.1 in the iv- and po-dosed
      animals for AZ and from 96.7 to 140.3 in the iv- and po-dosed groups for DAZ,
      respectively, indicate the capacity of the lung ("target tissue") for
      preferential uptake of the drug and its active metabolite. The efficiency of the
      desmethyl metabolite uptake into the lung was about 6-fold greater than that of
      AZ. The clearance of AZ from the body was faster than that of DAZ following
      either po or iv administration. The estimated availability of the AZ oral dose in
      guinea pigs was 0.19, which suggested that AZ was subjected to an extensive
      hepatic first-pass metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356731
TI  - Metabolism of [14C]azelastine in guinea pigs.
AB  - A specific HPLC separation method was used to generate 14C metabolite profiles in
      lung, muscle, and liver tissue and in bile, urine, and feces obtained from male
      guinea pigs that received a single oral dose of 1 mg/kg [14C]azelastine. Profiles
      were also generated in urine and feces of animals that received a single iv dose
      of labeled drug. In lung and muscle tissue, azelastine (AZ) and
      desmethylazelastine (DAZ) were the major components of 14C radioactivity. The
      amount of the amino acid metabolites (2- and 7-ACID), formed by oxidation and
      azepinyl ring opening, was relatively small. In the liver significant amounts of
      the 7-ACID were observed in addition to AZ and DAZ. The major metabolite in bile,
      urine, and feces was the 7-ACID, with much less AZ and DAZ present. The balance
      of 14C in the form of AZ and three metabolites in excreta (percentage of dose)
      was: AZ, 9.7-10.5%; DAZ, 8.7-9.6%; 2-ACID, 2.9-3.0%; and 7-ACID, 43.0-54.6%. No
      large differences in the quantitative profile between the two dosing routes were
      observed.

PMID- 1356732
TI  - Total body and hepatic clearance in rats of recombinant tissue-type plasminogen
      activator expressed in mouse C127 and Chinese hamster ovary cells.
AB  - The total body and hepatic clearance of two recombinant human tissue-type
      plasminogen activators (t-PA) produced in mouse C127 cells [t-PA(C127)] and in
      Chinese hamster ovary cells [t-PA(CHO)] were determined in rats. Recombinant t-PA
      was administered as a constant iv or intraportal venous infusion for 60 min. The
      plasma t-PA level over 120 min was measured by an ELISA. Whole-body
      pharmacokinetics were characterized in terms of the total body clearance (CLt),
      total volume of distribution, and mean residence time in the body. Hepatic
      disposition was described by the hepatic clearance (CL(hep)) and the mean
      hepatoportal transit time. Whereas a marked hepatic extraction was observed with
      both t-PAs, the estimated CL(hep) accounted for only one-half the Clt. No
      elimination took place in the lung, because no difference was observed between iv
      and intraarterial administration. Extrahepatic elimination, such as that in
      circulating blood, appeared to play a significant role in the disposition of t-PA
      in vivo. t-PA(C127) is known to possess the Gal alpha 1-3Gal epitope in its
      complex-type carbohydrate chains, whereas this structure is not involved in t
      PA(CHO). In the presence of Bandeiraea simplicifolia lectin I isolectin B4, which
      is specific to the Gal alpha 1-3Gal, the Clt of t-PA(C127) was significantly
      decreased, whereas that of t-PA(CHO) was unchanged. These results imply that the
      formation of a high molecular weight complex by this carbohydrate epitope
      effectively reduces the rate of catabolism of t-PA in vivo.

PMID- 1356733
TI  - Effects of low-density lipoprotein and ethinyl estradiol on cyclosporine
      metabolism in isolated rat liver perfusions.
AB  - The effects of low-density lipoprotein (LDL) on cyclosporine (CyA) metabolism
      were studied in the isolated perfused rat liver, in a recirculating mode, using
      Krebs-Ringer buffer in the absence (control perfusion) or presence of LDL (1
      microM) (LDL perfusion). In the LDL perfusions, CyA concentrations at all
      sampling times were about 2-fold higher, whereas the biliary excretion of CyA and
      measured metabolites (AM1, AM9, AM1c, and AM4N) were all lower than those
      obtained with the control perfusions. At the end of the perfusion (3 hr), the
      percentage of total CyA remaining (liver, bile, and perfusate) was significantly
      higher (76 +/- 1.2% to 85 +/- 2.4%) and the percentage of dose metabolized to AM9
      was lower (4.8 +/- 1.2% to 2.4 +/- 0.6%) in the LDL perfusions (N = 4). These
      results further suggest the inhibitory effects of LDL on CyA uptake, and,
      thereby, its metabolism as we observed previously in isolated rat hepatocyte
      studies. Because ethinyl estradiol (EE) is known to increase LDL receptors in
      rats, we investigated the possible involvement of LDL receptors in transporting
      CyA into liver cells using rats pretreated with EE (5 mg/kg/day sc for 5 days).
      The effects of LDL in maintaining CyA perfusate concentrations, and in decreasing
      biliary excretion of CyA and its metabolites in the EE-treated animals, were in
      the same direction as those noted in animals without EE, but the differences due
      to LDL were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356734
TI  - Tissue disposition of glyceryl trinitrate, 1,2-glyceryl dinitrate, and 1,3
      glyceryl dinitrate in tolerant and nontolerant rats.
AB  - The tissue distribution of glyceryl trinitrate (GTN) and its two dinitrate
      metabolites 1,2-glyceryl dinitrate (1,2-GDN) and 1,3-glyceryl trinitrate (1,3
      GDN), was studied in GTN-tolerant and nontolerant male Sprague-Dawley rats. The
      concentrations of GTN, 1,2-GDN, and 1,3-GDN were measured in plasma, heart,
      brain, liver, aortic tissue, and adipose tissue at various time points after a
      subcutaneous dose of GTN (50 mg/kg). At the first time point (5 hr),
      concentrations of GTN, 1,2-GDN, and 1,3-GDN in plasma were equal for tolerant and
      nontolerant rats, but the elimination rate was altered for the tolerant rats as
      compared with nontolerant rats. In adipose tissue, the concentration of GTN was
      significantly higher as compared with concentrations of the dinitrate
      metabolites. In contrast, the other tissues studied showed significantly higher
      concentrations of the GDNs when compared with GTN. The 1,3-GDN/1,2-GDN ratio
      decreased with time for both tolerant and nontolerant rats. This study indicates
      that long-term GTN administration results not only in tolerance development, but
      also in altered pharmacokinetics of GTN, 1,2-GDN, and 1,3-GDN. The results also
      show that the 1,3-GDN/1,2-GDN ratio is dependent on the GTN concentration.

PMID- 1356735
TI  - Correlation between N-acetyltransferase activities in uroepithelia and in vivo
      acetylator phenotype.
AB  - The relationship between in vivo acetylator phenotype of individuals and N
      acetyltransferase (NAT) activity in the cytosol of their cultured uroepithelia
      was examined in four urology patients. In vivo acetylator phenotypes were
      assigned by determining the ratio of N-acetyl vs. total [N-acetyl+free]
      sulfamethazine in urine and blood following a single oral dose (1 gm) of
      sulfamethazine. From the same patients, a surgical specimen of the ureter was
      obtained, uroepithelial cells were cultured in vitro, and the cytosols prepared.
      NAT activities were determined by measuring the amount of 4-acetylaminobiphenyl
      formed from incubation of uroepithelial cytosol with the substrate, 4
      aminobiphenyl, and the cofactor [14C]acetyl coenzyme A. The two individuals
      phenotyped as "slow acetylators" by the in vivo method had NAT activities of 8.3
      and 16.2 pmol 4-acetylaminobiphenyl/mg protein/min. In contrast, the two
      individuals phenotyped as "rapid acetylators" showed activities of 50.9 and 109.5
      pmol 4-acetylaminobiphenyl/mg protein/min. The rapid acetylators exhibit about 6
      fold greater uroepithelial NAT activities than slow acetylators, thus showing a
      direct correlation between the NAT activity in the uroepithelium, the target
      tissue of the human bladder carcinogen 4-aminobiphenyl, and the in vivo
      acetylator phenotype. These results imply that susceptibility of individuals to
      arylamine-induced bladder cancer might be associated with NAT activities in their
      target cells and that in vivo acetylator phenotyping could serve as a useful and
      relevant biochemical screening marker to assess the risk of developing bladder
      cancer.

PMID- 1356737
TI  - Effect of miconazole on warfarin disposition in rabbits.
AB  - To elucidate the mechanism underlying the reported potentiation of warfarin
      anticoagulant action after initiation of miconazole therapy, the effects of acute
      and chronic miconazole administration on warfarin disposition were examined in
      six adult New Zealand male rabbits. The rabbits received a 3.5 mg/kg iv dose of
      warfarin either alone, 1 hr after a single 100 mg/kg ip miconazole dose, or on
      day 5 of a 6-day 50 mg/kg/12 hr ip miconazole dosing regimen. Acute miconazole
      administration decreased the elimination rate constant of warfarin, but other
      warfarin disposition parameters were not altered. Chronic miconazole
      administration caused a 47% increase in warfarin plasma-free fraction (probably
      caused by competitive or noncompetitive protein binding displacement by
      miconazole metabolites) and a 42% decrease in warfarin intrinsic clearance
      (probably caused by a miconazole-induced inhibition in warfarin metabolism). As a
      consequence of these quantitatively similar but opposite changes, the total body
      clearance of warfarin (a low clearance drug) was marginally decreased. A
      significant decrease in the elimination rate constant and an increase in the
      tissue-free fraction of warfarin were also observed during chronic miconazole
      treatment. These results suggest that chronic miconazole administration should
      not significantly affect the steady-state plasma concentrations of total
      warfarin, but should increase the steady-state plasma concentrations of free
      warfarin. The expected increases in the steady-state plasma concentrations of
      free, pharmacologically active warfarin may account for the reported potentiation
      of the pharmacological action of warfarin when coadministered with chronic
      miconazole. Measurement of total plasma concentrations, and estimation of total
      body clearance might be misleading, and inadequate in identifying certain drug
      interactions involving low clearance drugs.

PMID- 1356736
TI  - 12 alpha-hydroxytestosterone. A hitherto unidentified testosterone metabolite
      produced by cytochrome P-450 2A2.
AB  - Several cytochrome P-450 enzymes are able to hydroxylate testosterone to many
      different metabolites, some of which remain to be identified. One hitherto
      unidentified metabolite represents a major metabolite of P-450 2A2, present in
      the liver of adult male rats, and a minor metabolite of several other cytochrome
      P-450 enzymes. Using the techniques of HPLC and GC/MS, we have obtained
      unequivocal evidence that this metabolite is 12 alpha-hydroxytestosterone.

PMID- 1356738
TI  - 3'-azido-3'-deoxythymidine drug interactions. Screening for inhibitors in human
      liver microsomes.
AB  - Zidovudine is a widely used antiretroviral drug active against human
      immunodeficiency virus. The drug interactions of this compound, which are
      primarily eliminated as a glucuronide, have not yet been extensively studied.
      Because zidovudine is frequently combined with other drugs, complete knowledge of
      interactions is essential to optimize AIDS therapy. We therefore screened the
      effect of 55 molecules, representative of 20 different therapeutic classes, on 3'
      azido-3'-deoxythymidine (AZT) glucuronidation by human liver microsomes. We
      demonstrate that many drugs caused more than 15% inhibition of AZT
      glucuronidation in vitro, whereas major antibiotics (ceftazidine, isoniazid,
      aminoglycosides, macrolides, and sulfamides), antivirals (2',3'-dideoxycytidine,
      2',3'-dideoxyinosine, and acyclovir), flucytosine, metronidazole, acetaminophen,
      and ranitidine had no effect. For compounds that appeared to inhibit AZT
      glucuronidation, extrapolation to the clinical situation must take into account
      both the in vitro apparent Ki values and the usual expected plasma level for the
      coadministered drug. By considering these parameters, this work indicates that
      clinically relevant inhibition of AZT glucuronidation may be observed with the
      following drugs: cefoperazone, penicillin G, amoxicilin, piperacillin,
      chloramphenicol, vancomycin, miconazole, rifampicin, phenobarbital,
      carbamazepine, phenytoin, valproic acid, quinidine, phenylbutazone, ketoprofen,
      probenecid, and propofol. Complementary clinical and pharmacokinetic studies
      should be performed to validate these assumptions.

PMID- 1356739
TI  - Pharmacokinetic analysis of enterohepatic circulation of 4-[2-(4
      isopropylbenzamido)ethoxy]benzoic acid. Effect of intramolecular rearrangement of
      its acyl glucuronide.
AB  - The enterohepatic circulation of 4-[2-(4-isopropylbenzamido)ethoxy]benzoic acid
      (PBAB) was studied in rats after an iv administration of 30 mg/kg. After the
      bolus injection, the PBAB concentrations in the plasma decreased rapidly, then
      increased to a peak concentration at 4 hr. Over a 6-hr period, 52% of the dose
      (Fe) was excreted in the bile as 1 beta-O-acyl glucuronide of PBAB (1 beta-PG).
      Elimination of PBAB from the plasma of bile duct-cannulated rats was more rapid
      than for the sham-operated rats. These results suggest that PBAB undergoes
      enterohepatic circulation. The equation for an enterohepatic circulation model
      was fitted to the plasma PBAB concentrations for intact rats using the program
      MULTI (FILT) to estimate the single circulating fraction (Fc) (bile----intestine-
      --systemic circulation). The Fc value was 0.072, which means that 7.2% of the
      dose was reabsorbed to systemic circulation during the first cycle. The fraction
      (Fa) reabsorbed from small intestine to systemic circulation during first cycle
      can be estimated by the formula Fa = Fo/Fa. The Fa value obtained was 14% of the
      dose, which was smaller than the Fa' (26% of the dose) standing for systemic
      availability of PBAB after oral dosing. When 1 beta-PG was incubated with bile
      for 2 hr, 79% was transformed to beta-glucuronidase-resistant isomers by
      intramolecular acyl migration. We consider that the acyl migration of 1 beta-PG
      in the small intestine or bile causes the difference between Fa and Fa' values,
      and decreases the enterohepatic circulation of PBAB.

PMID- 1356740
TI  - Pharmacokinetics and tissue distribution of human urinary tumor necrosis factor
      binding protein in mice.
AB  - Iodinated natural human urinary tumor necrosis factor binding protein I (125I
      uTBP) was iv injected into BALB/c mice, and its pharmacokinetics and tissue
      distribution were assessed during a short-term (0-1 hr) and for a long-term (0-24
      hr) period. The blood 125I-uTBP concentration displayed a biphasic pattern that
      was adequately described by a biexponential function with estimated half-lives of
      0.1 and 3.8 hr. The apparent volume of distribution (Vc) of the central
      compartment was 3 ml, which approximated the mouse blood volume. The clearance
      (CL) derived either from a model-dependent or a model-independent method of
      analysis was 2.5 and 2.9 ml/hr, respectively. One hr after the iv administration
      of 125I-uTBP, the radioactivity accumulated in the major organs and tissues. The
      highest concentrations in terms of pg per organ were seen in the skin and in the
      liver. When expressed as pg 125I-uTBP per mg organ, the distribution was the
      highest in the gallbladder, bladder, kidneys, and lungs. At 24 hr, the
      distribution of 125I-uTBP represented about 10% of the amount measured at 1 hr.
      The rank order of accumulation of the radiolabeled uTBP in the major organs,
      expressed as pg per organ at 24 hr was skin greater than liver greater than
      kidneys greater than lungs greater than gut greater than spleen greater than
      gallbladder.

PMID- 1356741
TI  - Identification of urinary metabolites of 8-methyl-8-azabicyclo-[3,2,1] octan-3-yl
      3,5-dichlorobenzoate (MDL 72,222) in the dog and monkey.
AB  - The metabolism of 8-methyl-8-azabicyclo- 3,2,1]octan-3-yl 3,5-dichlorobenzoate
      (MDL 72,222) was studied in the dog and monkey. Four urinary metabolites were
      detected by HPLC, HPLC/MS, and GC/MS, and were identified by comparison to
      authentic standards. The major metabolite in the dog, approximately 41% of the
      administered dose excreted between 0 and 120 hr, was the MDL 72,222-N-oxide. On
      the other hand, the major metabolite in the monkey was the glycine conjugate of
      3,5-dichlorobenzoic acid (greater than 56% of the dose). Seven percent of the
      dose in the monkey urine was free 3,5-dichlorobenzoic acid. N-Desmethyl MDL
      72,222 was present at 2.5 and 1% in the dog and monkey, respectively. Very little
      (less than 1%) of the parent compound was found in urine. The major pathways of
      metabolism of MDL 72,222 are N-oxidation, N-demethylation, ester hydrolysis, and
      amino acid conjugation.

PMID- 1356742
TI  - Pharmacokinetics and metabolism of the 5-hydroxytryptamine antagonist tropisetron
      after single oral doses in humans.
AB  - Tropiestron is a potent and selective antagonist of 5-hydroxytryptamine
      receptors. Tropisetron was developed for the indication of cancer chemotherapy
      induced emesis. The pharmacokinetic and metabolic dispositions of tropisetron
      were studied in 12 healthy male volunteers receiving a single oral dose of 62 or
      312 mumol (20 or 100 mg) of [14C]tropisetron. Serial plasma samples and complete
      urine and feces were collected for 120 hr postdose. Whereas the absorption of
      oral doses of 62-312 mumol tropisetron was rapid and complete, bioavailability
      was estimated to be only 66% for the 312 mumol dose and 52% for the 62 mumol
      dose, apparently because of saturable first-pass metabolism. Maximal
      concentrations of tropisetron averaged 87 and 608 nM after doses of 62 and 312
      mumol, respectively, and the parent drug accounted for 21 and 36% of the
      radioactivity in AUC0-24 hr pools. Approximately 90% of the drug was metabolized
      before excretion, and approximately 70% of the dose was recovered in the urine.
      Following both the 62 and 312 mumol doses, the terminal half-life of tropisetron
      averaged 6-7 hr and that of total radioactivity was 10-11 hr. Tropisetron and its
      metabolites in plasma and urine were separated by gradient elution reversed-phase
      HPLC. Structures of eight metabolites were assigned on the bases of NMR and MS
      data. Tropisetron was metabolized by oxidative hydroxylation of the indole ring
      at positions 5, 6, and 7. The hydroxylated derivatives are further conjugated
      with glucuronic acid and sulfate. N-Oxygenation and oxidative N-demethylation at
      the tropinyl nitrogen also occur in trace amounts.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1356743
TI  - Renal handling of alendronate in rats. An uncharacterized renal transport system.
AB  - Alendronate (4-amino-1-hydroxybutylidene-1,1-bisphosphonate), an antiosteolytic
      agent, is currently under investigation in the treatment of a variety of bone
      diseases. Earlier studies from this laboratory have demonstrated that
      systemically administered alendronate is rapidly either taken up by bone tissues
      or excreted by the kidney, and that renal excretion is the only route of
      elimination. The purpose of this study is to characterize the renal handling of
      alendronate in rats by standard clearance procedures with inulin as a marker of
      glomerular filtration rate. Alendronate is highly bound to rat serum protein. The
      excretion of alendronate by the kidney is concentration-and dose-dependent, and
      saturable, indicating that it is secreted by an active transport mechanism. The
      secretory mechanism exhibits limitation of transport, with an apparent Tm of
      approximately 25 micrograms/min/kg. However, high doses of cimetidine, quinine,
      probenecid, and p-aminohippuric acid had no effect on the renal excretion of
      alendronate, suggesting that alendronate is not secreted by anionic or cationic
      transport systems. In contrast, alendronate clearance is inhibited by etidronate,
      another bisphosphonate, in a dose-dependent manner, implying that these two
      bisphosphonates compete for an as yet uncharacterized renal transport system. As
      expected, the renal excretion of alendronate is drastically reduced in rats with
      acute renal failure. As a consequence of renal impairment, alendronate
      accumulates in plasma, and the concentration of the drug in bone tissues
      increases significantly.

PMID- 1356744
TI  - Phenol sulfotransferase activity in rat liver parenchymal cells cultured on
      collagen gels.

PMID- 1356745
TI  - Metabolism of alachlor by rat and monkey liver and nasal turbinate tissue.

PMID- 1356746
TI  - [Circadian variations in vascular tone].

PMID- 1356747
TI  - [Aminosalicylates in chronic inflammatory intestinal diseases and rheumatoid
      arthritis].

PMID- 1356748
TI  - [The metabolic side effects of beta-receptor blockers].

PMID- 1356749
TI  - Tetrahydrobiopterin-dependent functional recovery in 6-hydroxydopamine-treated
      rats by intracerebral grafting of fibroblasts transfected with tyrosine
      hydroxylase cDNA.
AB  - Fibroblasts (NRK-49F) were transfected with human type 2 tyrosine hydroxylase
      (TH; EC 1.14.16.29) cDNA, to clarify the mechanism involved in amelioration of
      parkinsonism by intracerebral grafting of catecholaminergic neurons and to
      investigate its possible use as a donor material. These genetically manipulated
      fibroblasts did not develop into a mass of tissue, and survived well in the host
      striatum. Expression of the TH minigene in the cells was successful even when
      they were transplanted into the host brain. Intracerebral microdialysis revealed
      that a measurable amount of L-3,4-dihydroxyphenylalanine (L-DOPA) was not
      spontaneously released from the implanted cells into the host striatum. However,
      release of a large amount of L-DOPA from the cells was observed when (6R)-L
      erythro-5,6,7,8-tetrahydrobiopterin (BH4) was perfused through a dialysis probe.
      Finally, we investigated whether these BH4-dependent L-DOPA-secreting fibroblasts
      are able to ameliorate the abnormal behavior of 6-hydroxydopamine-treated rats.
      Apomorphine-induced rotating behavior was not reversed by the grafting alone,
      whereas a marked reduction in drug-induced circling was observed temporarily
      after BH4 was perfused around the implanted cells. These findings indicate that
      TH cDNA-transfected non-neuronal cells might be able to be used as donor material
      for intracerebral grafting and ameliorate the abnormal behavior of rats with
      experimental Parkinson's disease.

PMID- 1356750
TI  - The fimbriae-like structures on V. cholerae isolated in Kenya.
AB  - For Vibrio cholerae 01 to overcome the normal intestinal clearing mechanisms and
      facilitate colonization in the host gut, fine filamentous structures covering the
      surface of all the cell must exist. These fimbriae-like structures were
      investigated in this study. Selection of the K23 V. cholerae 01 biotype el-tor
      isolated in Kisumu, Kenya, was based on its proteinase activity and ability to
      agglutinate 0.2M ammonium sulphate. This strain was cultured in modified tryptone
      broth pH 8.4, at 37 degrees C overnight. Electron microscopy of the strain
      revealed the presence of fimbriae-like structures which varied in number. Some
      cells showed more than 200, whereas in other cells only several filamentous
      structures were detected. It is suggested that these structures could be a
      possible candidate for a cholera vaccine.

PMID- 1356751
TI  - Advances in perinatal medicine. Proceedings of the 1st International Congress of
      Perinatal Medicine. Tokyo, 5-8 November 1991.

PMID- 1356752
TI  - Molecular biological approaches to genetic disorders in prenatal diagnosis.
AB  - DNA analysis of Duchenne muscular dystrophy (DMD) and hemophilia A was performed
      with the aim of establishing the most efficient and reliable method for carrier
      and prenatal diagnosis in the Japanese population.

PMID- 1356753
TI  - Reversal of flutamide-induced cryptorchidism by prenatal time-specific androgens.
AB  - The recent discovery of time-specific antiandrogens (flutamide) to induce
      undescent of the testes has provided us the ability to study androgen therapy for
      cryptorchidism in the first specific antiandrogen animal model for testicular
      descent. Postpartal administration of pharmacological doses of testosterone,
      dihydrotestosterone, or human chorionic gonadotropin failed to reverse
      antiandrogen-induced cryptorchidism. Reduction in the frequency of testicular
      undescent occurred only when these agents were administered before parturition.
      Indeed, statistically significant reductions in the incidence of undescended
      testes occurred only when androgens were administered simultaneously with the
      antiandrogens on gestational days 16-17. However, the successful ability of
      prenatal dihydrotestosterone or testosterone to prevent cryptorchidism was
      associated with significant complications of prenatal androgen therapy.
      Specifically, 100% (46 of 46) of the animals that had inhibition of flutamide
      induced cryptorchidism manifested findings of hypogonadotropic hypogonadism. The
      findings of descended diminutive testes and epididymis in these latter animals
      did, however, substantiate that testicular weight does not play a significant
      role in descent of this organ. In summary, these studies delineate a narrow
      window of time in which androgens act to effect testicular descent that is
      independent of testicular size.

PMID- 1356754
TI  - Dopamine and somatostatin inhibition of prolactin secretion from MMQ pituitary
      cells: role of adenosine triphosphate-sensitive potassium channels.
AB  - The sulfonylurea glibenclamide, which is known to block ATP-sensitive potassium
      channels, increases, in a dose-dependent manner, the release of PRL from MMQ
      pituitary cells. Glibenclamide does not reduce the dopaminergic inhibition of
      forskolin-stimulated PRL secretion; conversely it almost completely abolishes the
      inhibitory effect of somatostatin (SRIF) on this parameter. The sulfonylurea dose
      dependently increases basal [Ca++]i, without affecting the increase in [Ca++]i
      induced by high concentrations of extracellular potassium. Glibenclamide does not
      modify dopamine-induced [Ca++]i reduction, whereas it abolishes the inhibitory
      effect of SRIF on basal [Ca++]i. In the presence of diazoxide, an opener of ATP
      sensitive potassium channels, which lowers basal [Ca++]i, dopamine still reduces
      [Ca++]i whereas SRIF does not induce a further decrease. Glibenclamide induces
      the depolarization of the cell membrane and prevents the SRIF-evoked
      hyperpolarization. The hyperpolarization of the cell membrane induced by dopamine
      is not modified by glibenclamide. Diazoxide induces a cell membrane
      hyperpolarization that is enhanced by dopamine but not by SRIF. Finally,
      glibenclamide does not affect basal and stimulated adenylate cyclase activity. In
      conclusion, our findings show that, in MMQ cells, glibenclamide stimulates PRL
      release, suggesting an involvement of ATP-sensitive potassium channels in the
      regulation of PRL secretion. The reversal by glibenclamide of the effects of SRIF
      on calcium homeostasis, membrane potential, and PRL release suggests that this
      type of potassium channel participates to the somatostatinergic inhibition of PRL
      secretion. Conversely, we found that glibenclamide does not modify the
      dopaminergic inhibition of PRL secretion and second messenger systems, suggesting
      that ATP-sensitive potassium channels may not be involved in the inhibitory
      effect of dopamine on PRL release.

PMID- 1356755
TI  - Endoscopic laser lithotripsy with an automatic stone recognition system for
      basket impaction in the common bile duct.
AB  - In a patient with a common bile duct stone 28 mm in diameter, the traction wires
      of two basket catheters fractured during endoscopic mechanical lithotripsy.
      Disintegration of the concrement and removal of the impacted baskets failed even
      after extracorporeal application of 8,000 shockwaves. Pulsed dye laser
      lithotripsy was carried out via a 250 microns fiber which was advanced to the
      stone through a 6 French ERCP guiding catheter. Lithotripsy could be safely
      performed under fluoroscopic control since the laser used provides an automatic
      cut-out system upon tissue contact. 3,600 of 11,800 applied pulses were emitted
      with the total power setting and complete disintegration of the calculus was
      achieved. The baskets and the fragments could be removed endoscopically in the
      same session. Laser lithotripsy with a stone recognition system would seem to
      improve the applicability and safety of intracorporeal lithotripsy even when
      performed without direct visual guidance.

PMID- 1356756
TI  - Education and training in gastroenterology--recommendations from the OMGE
      Workshops, at the International Congresses of Gastroenterology, Rome, 1988, and
      at the World Congresses, Sydney, Australia 1990.

PMID- 1356757
TI  - Proceedings of the 1st International Symposium on Computers in Endoscopy. Munich,
      June 14, 1991.

PMID- 1356758
TI  - Proceedings of the National Working Conference on Smoking and Body Weight.
      Memphis, Tennessee, September 10-13, 1990.

PMID- 1356759
TI  - In vitro and in vivo characterization of the NMDA receptor-linked strychnine
      insensitive glycine site.
AB  - Modulation of the NMDA receptor by the strychnine-insensitive glycine site was
      studied both in vitro and in vivo. In vitro the glycinergic stimulation of
      [3H]MK801 binding was measured in three different rat forebrain membrane
      preparations. An increased association rate of [3H]MK801 in the presence of
      glycine was observed. The binding of the radioligand was also enhanced by D
      serine, whereas L-serine was less potent. The concentration-effect curves were
      shifted to the right by the glycine antagonist 7-chlorokynurenic acid (7CKA). In
      vivo modulation of the N-methyl-D-aspartate (NMDA) receptor was studied using
      NMDA induced convulsions in 7 day old rats. The NMDA effect was blocked by (+)-5
      methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten,5,10-imine maleate (MK801) and D
      (-)-2-amino-5-phosphono-pentanoic acid (AP5). The effect of a submaximal dose of
      NMDA was dose-dependently potentiated by 1-10 mg/kg D-serine, whereas higher
      doses of L-serine were needed to obtain a similar effect. 7CKA did not affect
      NMDA-induced convulsions but reduced the D-serine potentiation of NMDA responses.
      This study illustrates the ability of the strychnine-insensitive glycine site to
      modulate the NMDA receptor function both in vitro and in vivo.

PMID- 1356760
TI  - The contribution of AMPA and NMDA receptors to graded bursting activity in the
      hippocampal CA1 region in an acute in vitro model of epilepsy.
AB  - The AMPA/KA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and
      the NMDA receptor antagonist 2-amino-5-phosphonovalerate (D-APV) were used to
      investigate the contribution of excitatory amino acid (EAA) receptors to graded
      bursting activity recorded in the CA1 region of the rat hippocampal slice
      following bath application of the convulsant drug bicuculline methiodide (BIC, 2
      3 microM). CNQX (5-9 microM) significantly antagonised the burst in a reversible,
      concentration-dependent manner (n = 5). The effect involved a reduction in the
      amplitude but not the number of population spikes of the burst and also a
      depression of the underlying burst excitatory post-synaptic potential (EPSP). D
      APV (5-25 microM), in contrast, reduced the amplitude and number of spikes in the
      burst but had no effect on the burst EPSP (n = 5). Following a single
      concentration of CNQX (5 microM), applied in the presence of bicuculline, it was
      observed that the components of epileptiform response which remained could be
      completely abolished with D-APV (10 microM; n = 10). It was also shown that,
      following elimination of synaptic transmission with CNQX (5 microM), application
      of bicuculline (2-3 microM) induced a small burst that could be reversibly
      antagonised with D-APV (10 microM). These results show that evoked epileptiform
      activity witnessed in the presence of bicuculline involves the activation of both
      AMPA and NMDA receptors, the AMPA receptor activation making the major
      contribution. The burst mediated by NMDA receptors is not dependent on prior
      activation of AMPA receptors.

PMID- 1356761
TI  - Sharp anterior boundary of homeotic gene expression conferred by the fushi tarazu
      protein.
AB  - Parasegmental boundaries in the Drosophila embryo are delimited by the products
      of the fushi tarazu (ftz) and even-skipped (eve) genes. We show here that these
      act through particular key control regions of the homeotic gene Ultrabithorax
      (Ubx) to generate ftz- or eve-like stripe patterns of beta-galactosidase
      expression. Footprint analysis and tests in transformed embryos of constructs
      bearing mutated footprint regions suggest that ftz protein acts directly as a
      transcriptional activator of Ubx. Its activity outside the Ubx expression domain
      is suppressed by hunchback (hb), a repressor of Ubx. Some DNA binding sites for
      ftz protein are adjacent to, others overlap binding sites for hb protein, and we
      provide evidence that ftz protein competes with hb protein for DNA binding and/or
      for transcriptional activation. This competition mechanism results in a sharp
      anterior expression boundary. Direct activation of homeotic gene control regions
      by ftz (or eve) protein may be a regulatory step which is generally used to align
      expression of homeotic genes with parasegmental boundaries.

PMID- 1356763
TI  - An autoregulatory element of the murine Hox-4.2 gene.
AB  - Hox-4.2 promoter activity was assayed by transient expression assays in P19
      embryonal carcinoma (EC) cells. Cotransfection of a luciferase reporter gene
      construct driven by Hox-4.2 upstream sequences with an expression vector for the
      Hox-4.2 gene product resulted in a 20-fold increase in luciferase activity. This
      activity was specific in that the Hox-1.6 gene product had no effect in the same
      assay. Mutational analysis defined a cis-acting element with enhancer function
      which conferred most of this increase. Activation was largely dependent on two
      TAAT/ATTA motifs within this 217 bp fragment and HOX-4.2 bound specifically to
      both of these motifs. The 217 bp element maps within a highly conserved region of
      the human Hox-4.2 gene (HOX4B) which has been shown to display spatial enhancer
      activity in mice and flies. These findings suggest a conserved autoregulatory
      mechanism for the control of Hox-4.2 expression.

PMID- 1356762
TI  - Two regulatory proteins that bind to the basic transcription element (BTE), a GC
      box sequence in the promoter region of the rat P-4501A1 gene.
AB  - The cDNAs for two DNA binding proteins of BTE, a GC box sequence in the promoter
      region of the P-450IA1(CYP1A1) gene, have been isolated from a rat liver cDNA
      library by using the BTE sequence as a binding probe. While one is for the rat
      equivalent to human Sp1, the other encodes a primary structure of 244 amino
      acids, a novel DNA binding protein designated BTEB. Both proteins contain a zinc
      finger domain of Cys-Cys/His-His motif that is repeated three times with sequence
      similarity of 72% to each other, otherwise they share little or no similarity.
      The function of BTEB was analysed by transfection of plasmids expressing BTEB
      and/or Sp1 with appropriate reporter plasmids into a monkey cell line CV-1 and
      compared with Sp1. BTEB and Sp1 activated the expression of genes with repeated
      GC box sequences in promoters such as the simian virus 40 early promoter and the
      human immunodeficiency virus-1 long terminal repeat promoter. In contrast, BTEB
      repressed the activity of a promoter containing BTE, a single GC box of the
      CYP1A1 gene that is stimulated by Sp1. When the BTE sequence was repeated five
      times, however, BTEB turned out to be an activator of the promoter. RNA blot
      analysis showed that mRNAs for BTEB and Sp1 were expressed in all tissues tested,
      but their concentrations varied independently in tissues. The former mRNA was
      rich in the brain, kidney, lung and testis, while the latter was relatively
      abundant in the thymus and spleen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356764
TI  - A single amino acid substitution is sufficient to modify the mitogenic properties
      of the epidermal growth factor receptor to resemble that of gp185erbB-2.
AB  - The epidermal growth factor (EGF) receptor (EGFR) and the erbB-2 gene product,
      gp185erbB-2, exhibit distinct abilities to stimulate mitogenesis in different
      target cells. By using chimeric molecules between these two receptors, we have
      previously shown that their intracellular juxtamembrane regions are responsible
      for this specificity. Here we describe a genetically engineered EGFR mutant
      containing a threonine for arginine substitution at position 662 in the EGFR
      juxtamembrane domain, corresponding to threonine 694 in gp185erbB-2. This mutant,
      designated EGFRThr662, displayed affinity for EGF binding and catalytic
      properties that were indistinguishable from those of the wild type EGFR. However,
      EGFRThr662 behaved much as gp185erbB-2 in a number of bioassays which readily
      distinguish between the mitogenic effects of EGFR and gp185erbB-2. Moreover,
      significant differences were detected in the pattern of intracellular proteins
      phosphorylated on tyrosine in vivo by EGFR and EGFRThr662 in response to EGF.
      Thus, small differences in the primary sequence of two closely related receptors
      have dramatic effects on their ability to couple with mitogenic pathways.

PMID- 1356765
TI  - Differential DNA sequence recognition is a determinant of specificity in homeotic
      gene action.
AB  - The homeotic genes of Drosophila encode transcriptional regulatory proteins that
      specify distinct segment identities. Previous studies have implicated the
      homeodomain as a major determinant of biological specificity within these
      proteins, but have not established the physical basis of this specificity. We
      show here that the homeodomains encoded by the Ultrabithorax and Deformed
      homeotic genes bind optimally to distinct DNA sequences and have mapped the
      determinants responsible for differential recognition. We further show that
      relative transactivation by these two proteins in a simple in vivo system can
      differ by nearly two orders of magnitude. Such differences in DNA sequence
      recognition and target activation provide a biochemical basis for at least part
      of the biological specificity of homeotic gene action.

PMID- 1356767
TI  - Induction of the three peroxisomal beta-oxidation enzymes is synergistically
      regulated by dexamethasone and fatty acids, and counteracted by insulin in Morris
      7800C1 hepatoma cells in culture.
AB  - This work describes the molecular mechanism of hormonal modulation of fatty-acid
      peroxisomal beta oxidation in liver. Morris 7800C1 hepatoma cells and isolated
      hepatocytes were cultured in the presence of myristic acid (1 mM) and
      tetradecylthioacetic acid, a 3-thia fatty acid (50 microM), separately or in
      combination with dexamethasone (0.25 microM) or insulin (0.4 microM). Myristic
      acid stimulated acyl-CoA oxidase and a synergistic action was observed with
      dexamethasone. Parallel changes were recognized in enzyme protein and mRNA levels
      as quantified from immunoblots and Northern analyses. Myristic acid and
      tetradecylthioacetic acid had similar effects on this enzyme, while insulin
      inhibited the basal activity and blocked all inductions by the fatty acids and
      dexamethasone. Parallel mRNA and immunoblot analyses of the subsequent enzymes in
      the peroxisomal beta-oxidation pathway, enoyl-CoA hydratase/3-hydroxyacyl-CoA
      dehydrogenase/delta 3,delta 2-enoyl-CoA isomerase and 3-oxoacyl-CoA thiolase,
      showed an even stronger induction by tetradecylthioacetic acid and dexamethasone,
      while the counteraction by insulin was maintained in both 7800C1 hepatoma cells
      and hepatocytes. In hepatoma cells, the thiolase always showed the most
      pronounced induction (about 40-fold) after 14 days, with parallel changes in
      protein and mRNA levels. The results suggest that the changes in peroxisomal beta
      oxidation enzymes in 7800C1 hepatoma cells are due to a major effect on steady
      state mRNA levels giving rise to corresponding alterations in enzyme protein.
      These results may be explained by regulation at the level of transcription of
      corresponding genes, but mRNA stability changes and/or translational effects may
      also be of importance.

PMID- 1356766
TI  - A POU-A related region dictates DNA binding specificity of LFB1/HNF1 by orienting
      the two XL-homeodomains in the dimer.
AB  - LFB1/HNF1 regulates the hepatocyte-specific transcription of several genes,
      binding as a dimer to cis-acting elements that match the inverted palindrome
      GTTAATNATTAAC. The DNA binding domain of LFB1/HNF1 is characterized by a unique
      tripartite structure that includes an unusually long homeodomain (domain C), a
      region related to the POU-specific A-box (domain B) and a short N-terminal
      dimerization domain (domain A). We report that a recombinant peptide
      corresponding to the isolated homeodomain of LFB1/HNF1 binds as a monomer to a
      half-palindrome binding site, but shows diminished sequence specificity. Domain
      B, in addition to the homeodomain, is required and sufficient for proper
      recognition of LFB1/HNF1-responsive sites. A protein consisting of only these
      latter two domains is a monomer in solution, but forms dimers upon DNA binding.
      The protein-protein contacts established within the bound dimer restrain the
      orientation of the two homeodomains with respect to one another, thus
      contributing in a critical fashion to the recognition of the dyad symmetry
      related LFB1/HNF1 sites. The DNA-independent dimerization domain (domain A) is
      required to increase the affinity of DNA binding, but does not influence the
      dimer geometry.

PMID- 1356768
TI  - Regulation of recombinant human tyrosine hydroxylase isozymes by catecholamine
      binding and phosphorylation. Structure/activity studies and mechanistic
      implications.
AB  - Three isozymes of human tyrosine hydroxylase (hTH1, hTH2 and hTH4) were expressed
      in Escherichia coli and purified to homogeneity. Natural catecholamines and
      related synthetic compounds were found to be potent inhibitors, competitive to
      the tetrahydrobiopterin cofactor, of all the isozymes. Combining visible
      spectroscopy and equilibrium-binding studies, it was found that catecholamines
      bind to hTH1 and hTH2 with a stoichiometry of about 1.0 mol/mol enzyme subunit,
      interacting with the catalytic iron at the active site. All the isozymes tested
      were excellent substrates for cAMP-dependent protein kinase (Km = 5 microM, Vmax
      = 9.5 mumol.min-1.mg kinase-1). The incorporation of about 1.0 mol
      phosphate/subunit at Ser40 decreased the affinity of dopamine binding by a factor
      of 10. Conversely, the addition of stoichiometric amounts of Fe(II) and dopamine
      to the apoenzymes reduced both the affinity and stoichiometry of phosphorylation
      by cAMP-dependent protein kinase by 2-3-fold. These data provide evidence for a
      mutual interaction between the presumed regulatory and catalytic domains of hTH,
      and show that activation of the enzyme by phosphorylation and inactivation by
      binding of catecholamines are related events, which probably represent important
      mechanisms for the regulation of the enzyme activity in vivo.

PMID- 1356769
TI  - Evidence for an impaired long-chain fatty acid oxidation and ketogenesis in Fao
      hepatoma cells.
AB  - Fatty acid metabolism has been studied in Fao rat hepatoma cells. In basal
      conditions of culture, [1-14C]oleate is mainly esterified (85% of oleate uptake)
      in Fao cells, phospholipids being the most important esterified products (60% of
      oleate esterified). Addition of N6,O2'-dibutyryl-adenosine 3',5'-monophosphate
      (0.1 mM) in Fao cells does not change the metabolic fate of oleate whereas it
      induces gluconeogenesis and phosphoenolpyruvate carboxykinase mRNA accumulation.
      It is shown that the limitation of oleate oxidation is located at the level of
      the entry into mitochondria since octanoate is actively oxidized in Fao cells.
      Neither the activities of carnitine palmitoyltransferase (CPT) I and II nor the
      CPT II protein amount are affected by cAMP addition. The limitation of oleate
      oxidation in Fao cells results from (a) a high rate of lipogenesis and a high
      malonyl-CoA concentration, (b) a CPT I very sensitive to malonyl-CoA inhibition.
      The presence of an active oleate oxidation in mitochondria isolated from Fao
      cells confirms that CPT I is the limiting step of oleate oxidation. Moreover, Fao
      cells are unable to perform ketogenesis. This particular feature results from a
      specific deficiency in mitochondrial hydroxymethylglutaryl-CoA synthase protein,
      activity and gene expression. The metabolic characteristics observed in Fao cells
      could be a common feature in hepatoma cell lines with regard to the low capacity
      for long-chain fatty acid oxidation and ketone body production observed in the
      rat H4IIE and the human HepG2 cells.

PMID- 1356770
TI  - Lithium, an inhibitor of cAMP-induced inositol 1,4,5-trisphosphate accumulation
      in Dictyostelium discoideum, inhibits activation of guanine-nucleotide-binding
      regulatory proteins, reduces activation of adenylylcyclase, but potentiates
      activation of guanylyl cyclase by cAMP.
AB  - Li+ drastically alters pattern formation in Dictyostelium by inhibiting cAMP
      induced prespore-gene expression and promoting cAMP-induced prestalk-gene
      expression. We reported previously that Li+ inhibits inositol monophosphatases in
      this organism and strongly reduces basal and cAMP-stimulated inositol 1,4,5
      trisphosphate levels. We show here that Li+ also reduces cAMP-induced
      accumulation of cAMP, but promotes cAMP-induced accumulation of cGMP. This effect
      is not due to inhibition of cGMP hydrolysis or inhibition of adaptation and may
      therefore reflect stimulation of guanylyl-cyclase activation. Li+ does not affect
      the binding of cAMP to surface receptors but interferes with the interaction
      between receptors and guanine-nucleotide-binding regulatory (G) proteins. These
      effects are complex; in the absence of Mg2+, Li+ increases guanosine 5'-[gamma
      thio]triphosphate(GTP[S])-binding activity to similar levels as 1 mM Mg2+.
      However, while Mg2+ potentiates cAMP-induced stimulation of GTP[S]-binding
      activity, Li+ effectively inhibits stimulation. Li+ also inhibits cAMP
      stimulated, but not basal high-affinity GTP-ase activity, indicating an
      inhibitory effect on cAMP-induced activation of G-proteins. Our data suggest that
      in addition to inositolphosphate metabolism, the activation of G-proteins may be
      a second biochemical target for Li+ effects on pattern formation and signal
      transduction in Dictyostelium.

PMID- 1356771
TI  - Purification, cDNA cloning and Northern-blot analysis of mitochondrial chaperonin
      60 from pumpkin cotyledons.
AB  - Two different cDNA clones, pMCPN60-1 and pMCPN60-2, encoding the mitochondrial
      homologues of chaperonin 60 (Cpn60) were isolated from a cDNA library of
      germinating pumpkin cotyledons by use of mixtures of synthetic oligonucleotides
      based on the N-terminal amino acid sequence of the protein. Determination of the
      complete nucleotide sequences of the two cDNA revealed that pMCPN60-1 and pMCPN60
      2 each contain one open reading frame that encodes a protein of 575 amino acids
      with molecular masses of 61052 Da and 61127 Da, respectively. The deduced amino
      acid sequences of the two polypeptides include a 32-residue N-terminal putative
      mitochondrial presequence attached to the mature polypeptides, and they are 95.3%
      identical. From a comparison of deduced amino acid sequences with other Cpn60, it
      appears that the mature polypeptides of pumpkin mitochondrial Cpn60 are 44-59%
      identical to the other Cpn60, namely, GroEL of Escherichia coli, the 60-kDa heat
      shock protein (Hsp60) of mitochondria in the yeast Saccharomyces cerevisiae, P1
      protein of mammalian mitochondria and the Ribulose-1,5-bisphosphate
      carboxylase/oxygenase subunit-binding proteins alpha and beta of plastids in
      higher plants. Genomic Southern-blot analysis identified at least two copies of
      the gene for mitochondrial Cpn60 in the pumpkin genome. The levels of mRNA for
      mitochondrial Cpn60 in cotyledons, hooks and hypocotyls of pumpkin seedlings
      increased in response to heat stress, as deduced from Northern-blot analysis,
      indicating that pumpkin mitochondrial Cpn60 is a heat-induced stress protein.

PMID- 1356773
TI  - New multifactorial antihypertensive drugs and cardiovascular risk factors.
      Symposia proceedings. Milan, Italy, 6 June 1991 and Amsterdam, The Netherlands,
      20 August 1991.

PMID- 1356772
TI  - Haemodynamic effects of different doses of dopexamine hydrochloride in low
      cardiac output states following cardiac surgery.
AB  - We studied the haemodynamic effects of dopexamine hydrochloride, a beta 2
      adrenergic agonist with dopaminergic (DA1) activity, in 20 patients with low
      cardiac output following surgery for coronary artery bypass grafting and/or valve
      replacement or repair. Following titration of four doses (1, 2, 4 and 6
      micrograms.kg-1.min-1), the dose producing the optimal response was infused for
      up to 48 h (five patients). During the infusion, significant increases in cardiac
      index and stroke volume were accompanied by significant decreases in systemic
      vascular resistance. Heart rate increased significantly up to 6 h and thereafter
      returned to control levels. Mean blood pressure was reduced but did not fall
      below 60 mmHg. However, in five patients treated for 48 h mean blood pressure had
      returned to control levels. Unwanted effects (tachycardia and hypotension) were
      seen chiefly at higher doses, leading us to conclude that infusion rates of 4
      micrograms.kg-1.min-1 or less will be useful in the treatment of low cardiac
      output following cardiac surgery.

PMID- 1356774
TI  - Central mechanisms regulating blood pressure: circuits and transmitters.

PMID- 1356775
TI  - Favourable haemodynamic effects of a new multifactorial antihypertensive on left
      ventricular dimension, wall thickness and function in hypertensive patients.

PMID- 1356776
TI  - Effect of a new multifactorial antihypertensive on heart morphology and function
      in mild to moderate essential arterial hypertension.

PMID- 1356777
TI  - Metabolic effects of antihypertensive drugs interacting with the sympathetic
      nervous system.

PMID- 1356778
TI  - Clinical pharmacology, efficacy and safety of a new alpha 1 adrenoceptor
      antagonist with an additional central action, in hypertension.

PMID- 1356780
TI  - The heart in hypertension. Symposium. Zermatt, Switzerland, 23-25 January 1992.

PMID- 1356779
TI  - Influence of a new multifactorial antihypertensive on blood pressure and
      metabolic profile in essential hypertension associated with non-insulin-dependent
      diabetes mellitus.

PMID- 1356781
TI  - The role of beta receptor blockade in preventing sudden death.
AB  - The high mortality rate from coronary heart disease in hypertensives can only be
      substantially reduced if sudden coronary death rates can be decreased. The aim of
      this review is to discuss how treatment may be tailored to reduce the risk of
      sudden death in high-risk patients. Clinical trials have not yet produced long
      term primary prevention data on the effects of angiotensin converting enzyme
      (ACE) inhibitors, calcium antagonists or alpha-blockers on cardiovascular
      complications and sudden death in hypertensive patients. Further, the conclusion
      from large-scale secondary preventive studies presently available on ACE
      inhibitors and calcium antagonists is that their impact on sudden death has been
      disappointing. By contrast, some beta-blockers have reduced sudden death and
      other coronary events both in primary and secondary preventive studies. The
      benefits have been attributed to beta 1-blockade, and seem to be independent of
      blood pressure control. It cannot be assumed that all beta-blockers are equally
      effective in preventing ventricular fibrillation, sudden death and other coronary
      events. To date, the best documented data cover the lipophilic beta-blockers and
      it is speculated that by increasing levels of cardiac vagal tone and electrical
      stability in the heart, beta 1-blockade in the brain might contribute to the
      reduction in sudden death risk seen with these beta-blockers.

PMID- 1356782
TI  - Pharmacokinetics and first clinical experiences with an antihypertensive dopamine
      (DA2) agonist.
AB  - The pharmacokinetic properties and first clinical experiences with the
      antihypertensive dopamine (DA2) agonist, carmoxirole, are summarized. In man
      carmoxirole was rapidly absorbed. On oral administration the maximum plasma
      concentration was reached after 2-3 h. The drug was metabolized, mainly to an
      ester-type glucuronide, and was excreted (unchanged carmoxirole plus glucuronide)
      largely by the kidneys. The plasma half-life of the parent compound was 5.5 h.
      For the dose range tested (0.5 to 1.5 mg) the pharmacokinetics were linear. The
      drug was rapidly distributed in animals but only very small amounts penetrated
      the blood-brain barrier. Carmoxirole did not affect supine blood pressure in
      healthy subjects, but under the conditions of the Schellong's test some
      orthostatic reactions occurred with high doses. In patients the blood pressure
      was reduced for at least 8 h after single oral doses. On repeated administration
      for several weeks a relevant antihypertensive effect was still measurable 12 and
      24 h after dose. The most frequently reported adverse events have been headache,
      dizziness, tiredness, nausea, and gastric disorders. These symptoms are
      considered to be mainly due to blood pressure reduction, as is frequently
      observed at the beginning of antihypertensive therapy. In patients the incidence
      of orthostatic reactions is appreciably lower than in healthy subjects, and in
      both change of position was sufficient to relieve the symptoms.

PMID- 1356783
TI  - Pharmacological basis for antihypertensive therapy with a novel dopamine agonist.
AB  - In the past, nearly all major mechanisms involved in the regulation of blood
      pressure have become targets of antihypertensive drugs. They include the brain
      stem with its neuronal circuits of central cardiovascular regulation, the
      sympathetic neuro-effector system, the kidney, the renin angiotensin aldosterone
      system and the vascular smooth muscle cell. There are various ways of influencing
      the function of the sympathetic nervous system, but the clinical potential of one
      mechanism of action has not yet been explored in detail. Drugs that inhibit
      noradrenaline release through stimulation of inhibitory receptors located at
      adrenergic nerve terminals in the cardiovascular system (inhibitory presynaptic
      receptors) are not available for the treatment of hypertension. Among the
      multiple presynaptic receptors, dopamine receptors which belong to the dopamine2
      subtype, are of particular interest. Carmoxirole is a novel indole derivative
      with a potent agonist action selective for dopamine2-receptors of the periphery.
      Experimental evidence shows that carmoxirole lowers blood pressure in various
      models of hypertension mainly or exclusively through inhibition of noradrenaline
      release from sympathetic nerve endings. This effect of carmoxirole is mediated by
      presynaptic dopamine receptors with the characteristic that release inhibition is
      restricted to low rates of sympathetic nerve discharge.

PMID- 1356784
TI  - Molecular analysis of patients with Wiedemann-Beckwith syndrome. I. Gene dosage
      on the short arm of chromosome 11.
AB  - Wiedemann-Beckwith syndrome (WBS) is characterised by a specific group of
      congenital malformations associated with an increased concurrent risk for
      development of a defined group of childhood neoplasms. The mode of inheritance is
      complex, but recently compiled family data suggest that it is an autosomal
      dominant trait of varying expression. It has previously been suggested that major
      rearrangements on the short arm of chromosome 11 may be involved in the aetiology
      of the disease, particularly in the region of the insulin like growth factor II
      (IGF-II) gene (11p15.5). This gene is thought to be parentally imprinted in the
      mouse and it has been suggested that in the human, duplication of the non
      imprinted locus in WBS patient might lead to diploid expression of the gene and
      consequent general hyperplasia. This model predicts that there should be both
      frequent and parental origin specific duplication of the IGF-II gene in the
      patients. It was the aim of this study to examine the IGF-II locus and its
      surrounding chromosomal environment for such lesions in a large number of WBS
      patients. Using restriction fragment length polymorphism analysis for four linked
      markers on 11p and genomic clones internal to the IGF-II locus we could find no
      evidence of alteration or amplification of this area in any of the 11 patients
      investigated. In one patient who developed a Wilms tumour we could find no
      evidence for loss of any material on the short arm of chromosome 11 as reported
      previously.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356786
TI  - Regulation of interleukin-4 production in human mononuclear cells.
AB  - Interleukin (IL)-4 is a cytokine with a broad range of effects on immune cells,
      however, little is known regarding the regulation of its production in freshly
      isolated human peripheral blood mononuclear cells (PBMC). Here we report the
      production of IL-4 in such cells following stimulation with monoclonal antibodies
      (mAb) directed against different cell surface antigens. We show that triggering
      via CD2 is more efficient for IL-4 production than triggering via the CD3
      complex. The addition of a CD28 mAb enhances IL-4 production approximately
      threefold. Cell depletion experiments show that among CD2 plus CD28-stimulated
      PBMC the production of IL-4 is restricted to the CD8-CD45RA-T cell subpopulation.
      mAb interfering with the binding of IL-2 to its receptor can inhibit the
      production of IL-4 in CD2 plus CD28-stimulated PBMC. As IL-2 induces cell
      proliferation and production of interferon-gamma, but not production of IL-4, it
      follows that IL-2 is necessary but not sufficient for IL-4 production.

PMID- 1356785
TI  - Molecular analysis of patients with Wiedemann-Beckwith syndrome. II. Paternally
      derived disomies of chromosome 11.
AB  - In Wiedemann-Beckwith syndrome (WBS) a putative disease gene resides at the tip
      of the short arm of chromosome 11 in the region of the insulin growth like factor
      II (IGF-II) gene. Whilst changes in gene dosage in this area do not appear to be
      common in the syndrome, in familial cases the lesion appears to be dominant only
      when inherited through the female line. We undertook to examine the parental
      origin of the copies of chromosome 11 in a large group of WBS patients using a
      series of restriction fragment length polymorphisms (RFLPs) on 11p, and report
      here that in one sporadic case of WBS out of 14 both copies of chromosome 11 are
      derived from the father and are present in a normal dosage. This suggests that at
      least one mode of expression of the lesion is modified by genomic imprinting.

PMID- 1356787
TI  - The substituted amphetamines 3,4-methylenedioxymethamphetamine, methamphetamine,
      p-chloroamphetamine and fenfluramine induce 5-hydroxytryptamine release via a
      common mechanism blocked by fluoxetine and cocaine.
AB  - The abilities of the substituted amphetamines 3,4-methylenedioxymethamphetamine
      (MDMA), methamphetamine, p-chloroamphetamine (PCA) and fenfluramine to induce
      synaptosomal [3H]serotonin (5-HT) release were compared using a novel microassay
      system. The rank order of release potencies was found to be (+/-)PCA congruent to
      (+)-fenfluramine greater than (+)-MDMA much greater than (+)-methamphetamine.
      Combination of two drugs at their EC50 did not cause more release than either
      drug alone at an equivalent concentration. In addition, the 5-HT uptake blockers
      fluoxetine and cocaine inhibited the release induced by MDMA, methamphetamine,
      PCA and fenfluramine to the same percentage. However, threshold concentrations of
      the substituted amphetamines known to inhibit uptake did not attenuate the
      release caused by higher concentrations of these compounds. These results
      suggests that MDMA, methamphetamine, PCA and fenfluramine cause 5-HT release via
      a common mechanism. Furthermore, these results indicate that the 5-HT uptake
      blockade induced by these substituted amphetamines in vitro is different from
      that induced by either fluoxetine or cocaine.

PMID- 1356789
TI  - Effects of i.c.v. lithium chloride administration on monoamine concentration in
      rat mediobasal hypothalamus.
AB  - We investigated the acute effects of a single i.c.v. injection of lithium
      chloride (LiCl) the neuroamine content of the rat mediobasal hypothalamus (MBH).
      The effects of lithium on amine synthesis and degradation enzymes were also
      studied in vitro. Noradrenaline (NA), dopamine (DA), serotonin (5-HT) and 5
      hydroxyindoleacetic acid (5-HIAA) concentrations were reduced 10 min after i.c.v.
      injection of 24 nmol of LiCl and returned to control values 30 min after the
      injection. Two nmol of LiCl reduced the concentration of DA (10 and 30 min after
      injection) and 5-HIAA (30 min after injection). LiCl (0.5-10 mM) inhibited
      tyrosine hydroxylase activity (catecholamine synthesis) in vitro in a
      concentration dependent manner. The i.c.v. administration of a high dose of LiCl
      reduced the content of neuroamines in the MBH. This might result from and
      inhibition of synthesis. A possible link between the observed changes and some
      reported side effects of lithium therapy is discussed.

PMID- 1356788
TI  - Biochemical and pharmacological studies on pramipexole, a potent and selective
      dopamine D2 receptor agonist.
AB  - Pramipexole (SND 919; 2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-
      dihydrochloride) was tested for its agonistic activity at pre- and postsynaptic
      dopamine (DA) receptors. L-Dihydroxyphenylalanine (L-dopa) accumulation in the
      rat striatum and limbic system and the alpha-methyltyrosine-induced reduction of
      DA were inhibited. Both effects were fully antagonized by haloperidol but not by
      the selective DA D1 receptor antagonist SCH 23390. Pramipexole decreased the
      levels of DA metabolites dose dependently, whereas striatal DA levels remained
      unchanged. In mice, pramipexole (0.001-1 mg/kg s.c.) reduced exploratory
      locomotor activity. In rats with unilateral striatal lesions, only weak
      ipsilateral rotation was produced by pramipexole at the highest dose. However, in
      rats with unilateral lesions of the medial forebrain bundle, pramipexole potently
      induced contralateral circling (ED50 0.026 mg/kg s.c.). In the N-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) monkey model, pramipexole also had potent
      stimulatory effects. Finally, in haloperidol-sensitized monkeys, the substance
      did not elicit dyskinesia/dystonia when given alone, but rather inhibited those
      symptoms which had been induced by haloperidol (ED50 0.116 mg/kg i.m.). It is
      concluded that pramipexole has therapeutic potential for schizophrenic patients,
      as a result of its autoreceptor agonistic effects and its weak effects at
      normosensitive postsynaptic DA receptors. Furthermore, its potent stimulatory
      effects in DA-depleted animals suggest a possible use in the treatment of
      Parkinson's disease.

PMID- 1356790
TI  - The behavioural effects of MK-801 in rats: involvement of dopaminergic,
      serotonergic and noradrenergic systems.
AB  - The non-competitive NMDA receptor antagonist, MK-801 (dizocilpine), induces in
      rats a characteristic behavioural syndrome with ataxia, stereotypies and
      hyperlocomotion. At least part of this behavioural syndrome is thought to be
      related to interactions between glutamatergic and dopaminergic neurotransmission.
      Based on recent biochemical evidence that serotonin (5-HT) might also be involved
      in the effects of MK-801 several 5-HT receptor ligands were tested for effects on
      MK-801-induced behaviours. The 5-HT1A receptor ligands, ipsapirone and NAN-190,
      which are known to display antagonist-like properties in functional models of
      postsynaptic 5-HT1A receptor activity attenuated or blocked the hyperlocomotion
      and head weaving observed after administration of MK-801, whereas the 5-HT2
      receptor antagonist, ritanserin, was ineffective in this respect. The dopamine
      receptor antagonist, haloperidol, and the alpha 1-adrenoceptor antagonist,
      prazosin, also attenuated behaviours induced by MK-801. In contrast to its
      effects on stereotypies induced by MK-801, ipsapirone potentiated rather than
      attenuated the stereotyped behaviour induced by the dopamine receptor agonist,
      apomorphine, indicating that antagonism of MK-801-induced stereotypies by
      ipsapirone may not be related to the dopaminergic system. The data indicate that,
      in addition to catecholaminergic systems, serotonergic neurotransmission is
      significantly involved in the mechanisms by which MK-801 alters behaviour in
      rats.

PMID- 1356791
TI  - Resistance of beta 2-adrenoceptor-mediated responses of lung strips to
      desensitization by long-term agonist exposure--comparison with atrial beta 1
      adrenoceptor-mediated responses.
AB  - In vitro desensitization of beta 2-adrenoceptor-mediated relaxation of guinea-pig
      isolated parenchymal strips was examined. Concentration-response curves for
      isoprenaline were obtained and after long-term incubation with isoprenaline,
      followed by washout, a second curve was obtained. Correction for time-dependent
      loss of sensitivity was made from time-matched controls. After incubation with
      10(-5) M isoprenaline for 0.5, 1, 2, 4 and 8 h, loss of responsiveness of
      carbachol-contracted lung strips was observed after 4h as a reduced post
      incubation maximum response. When the concentration was reduced to 10(-6) M, a 4
      h incubation with 1 h washout no longer induced a shift of the post-incubation
      curve in carbachol-contracted lung strips. In contrast, lung strips with
      intrinsic tone displayed reduced responsiveness to isoprenaline after 4 h
      incubation with 10(-6) M isoprenaline. Incubation of the tissue for 4 h with
      lanthanum (1.4 x 10(-6) M), a relaxant not operating through beta 2-adrenoceptors
      or their effector coupling, had the same effect upon isoprenaline concentration
      response curves as incubation with isoprenaline. This was irrespective of whether
      intrinsic tone (10(-6) M isoprenaline) or carbachol-contracted (10(-5) M
      isoprenaline) lung strips were used. It was concluded that the loss of beta 2
      adrenoceptor responsiveness after incubation with 10(-6) M isoprenaline was due
      to the prolonged maximal relaxation of the tissue for 4 h rather than
      desensitization of the beta 2-adrenoceptor. Indeed, after correction for maximal
      relaxation and for time, no significant change in beta 2-adrenoceptor sensitivity
      of the lung occurred after incubation with 10(-6) M isoprenaline for 4 h. This
      contrasts with significant rightwards shifts of the concentration-response curves
      for the beta 1-adrenoceptor-mediated increases in rate and tension of guinea-pig
      right and left atria after identical incubation conditions. Thus whereas beta 1
      adrenoceptor-mediated responses displayed desensitization after long-term in
      vitro agonist exposure, the beta 2-adrenoceptor-mediated responses were
      resistant.

PMID- 1356792
TI  - Effects of beta-adrenoceptor blockers on mitochondrial ATPase activity in guinea
      pig heart preparations.
AB  - The effects of three beta-adrenoceptor blockers atenolol, indenolol and nadolol
      on myocardial mitochondrial ATPase (ATP: phosphohydrolase EC 3.6.1.3) activity
      were evaluated and compared with that of propranolol in guinea pig heart
      preparations. Propranolol and indenolol inhibited ATPase activity with IC50
      values of 4.4 +/- 0.5 and 5.3 +/- 0.4 mM, respectively. In contrast, however,
      nadolol and atenolol markedly enhanced mitochondrial ATPase activity. Atenolol
      increased the enzyme activity by approximately 5, 240 and 950%, while nadolol
      enhanced it by 13, 280 and 2800% at 100 microM, 1.0 mM and 10.0 mM, respectively.
      The results indicate that these drugs exhibit two modes of interaction with the
      mitochondrial ATPase: inhibition by propranolol and indenolol and stimulation by
      atenolol and nadolol. The inhibitory actions are probably related to the membrane
      stabilizing effects and therefore antiarrhythmic actions of the two drugs, while
      the stimulatory effects of atenolol and nadolol are probably a result of
      interactions with some component of oxidative phosphorylation or the respiratory
      chain.

PMID- 1356793
TI  - Beta-adrenergic regulation of amine precursor amino acid transport across the
      blood-brain barrier.
AB  - Beta-Adrenoceptor agonists were administered i.p. into rats and amino acid levels
      in brain and plasma were then determined to assess the effects on transport
      across the blood-brain barrier. Isoproterenol (10 mumol/kg) caused significant
      increases in aromatic amino acid (tyrosine, phenylalanine and tryptophan) levels
      in cerebral cortex and decreases in almost all amino acid concentrations in
      plasma. This effect of isoproterenol on brain tyrosine level was dose-dependent
      with an ED50 of 0.25 mumol/kg. Salbutamol (beta 2-adrenoceptor agonist, 10
      mumol/kg) showed similar effects, but dobutamine (beta 1-adrenoceptor agonist, 50
      mumol/kg) failed to increase brain amino acid levels. When 1-threo-3,4
      dihydroxyphenylalanine (L-DOPA, 100 mumol/kg) was i.p. loaded, beta-adrenoceptor
      agonists promoted the transport of L-DOPA into brain without increasing the
      clearance rate of plasma L-DOPA. Moreover, significant increases in dopamine and
      its metabolites were observed in rat brain. These findings suggest that the
      transport of aromatic amino acids across the blood-brain barrier may be regulated
      through beta 2-adrenoceptors and that co-administration of beta 2-adrenoceptor
      agonists with L-DOPA may enhance the therapeutic efficacy of L-DOPA.

PMID- 1356794
TI  - Evidence that an alpha 2A-adrenoceptor subtype mediates antinociception in mice.
AB  - In the hot-plate test in mice, the antinociceptive action of the alpha 2
      adrenoceptor agonist, UK 14,304, was abolished by the alpha 2-adrenoceptor
      antagonist, idazoxan, the potent alpha 2A-adrenoceptor antagonist, RX 821002 and
      the preferential alpha 2A-adrenoceptor antagonist, BRL 44408. In contrast, the
      preferential alpha 2B- (and alpha 2C)-adrenoceptor ligands ('antagonists'), ARC
      239, BRL 41992 and prazosin were inactive. The preferential alpha 2A-adrenoceptor
      partial agonist, guanfacine, partially inhibited UK 14,304-induced
      antinociception. Further, guanfacine BRL 44408 reversibly elicited submaximal
      antinociception. It is concluded that alpha 2A-adrenoceptors mediate
      antinociception in mice.

PMID- 1356795
TI  - In vitro study of a novel atypical beta-adrenoceptor agonist, SM-11044.
AB  - SM-11044 (L-threo-3-(3,4-dihydroxyphenyl)-N-[3-(4-fluorophenyl) propyl] serine
      pyrrolidine amide hydrobromide) stimulated the relaxation of guinea pig ileum
      (EC50: 3.0 x 10(-8) M), trachea (EC50: 1.3 x 10(-7) M), lung parenchyma (EC50:
      2.1 x 10(-6) M) and the increase in right atrial rate (EC50: 6.9 x 10(-6) M). It
      also induced lipolysis of rat white adipocytes (EC50: 1.2 x 10(-6) M). Both the
      relaxant response of ileum and the lipolytic response of adipocytes to SM-11044
      were resistant to inhibition by propranolol (10(-6) M), but were antagonized by
      cyanopindolol (10(-6) M). In contrast, the responses to SM-11044 in trachea, lung
      parenchyma and right atrium were almost completely abolished by propranolol (10(
      6) M). Furthermore, the selectivity of SM-11044 relative to isoproterenol was
      ileum greater than adipocytes greater than trachea (beta 2) greater than lung
      (beta 2) greater than atrium (beta 1). These results suggest that SM-11044 is a
      selective agonist of atypical beta-adrenoceptors that are resistant to antagonism
      by propranolol but sensitive to cyanopindolol. The receptor binding and adenylate
      cyclase stimulating activity of SM-11044 were also examined on transfected
      Chinese hamster ovary cells expressing human beta 1-, beta 2- or beta 3
      adrenoceptors. SM-11044 inhibited the binding of [125I]iodocyanopindolol to the
      three types of receptors in a concentration-dependent manner. The selectivity in
      terms of Ki values was beta 3 (Ki: 1.3 x 10(-6) M) greater than beta 2 (Ki: 4.1 x
      10(-6) M) greater than beta 1 (Ki: 18.1 x 10(-6) M)-adrenoceptors.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1356796
TI  - NMDA receptor antagonists block cardiovascular responses to intrathecal
      administration of D-baclofen in the rat.
AB  - In previous studies we found that D and L-baclofen have different effects on
      sympathetic output when administered intrathecally, yet the actions of both
      enantiomers are blocked by intrathecal administration of phaclofen. The present
      experiments were done to determine the mechanism by which D-baclofen expresses
      its effects. In urethane-anaesthetized Sprague-Dawley rats, when D-baclofen was
      given intrathecally at the T9 spinal level following pretreatment with 2 nmol of
      the NMDA receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV), it
      increased systolic and diastolic arterial pressures (n = 7), as in the previous
      studies. However, after intrathecal administration of 10 nmol of APV,
      administration of D-baclofen had no effect on these parameters (n = 7).
      Intravenous administration of ketamine (7.5 mg/kg), another NMDA receptor
      antagonist, also blocked the effect of D-baclofen (n = 6) but it had no effect on
      the pressor responses produced by intrathecal administration of carbachol (27.4
      nmol; n = 6). In additional experiments, L-baclofen (70 nmol) had no effect on
      the increases in heart rate and arterial pressure produced by N-methyl-D-aspartic
      acid (NMDA) (2 nmol; n = 8). These results indicate that D-baclofen increases
      arterial pressure via an NMDA receptor-mediated mechanism, perhaps by provoking
      the release of an endogenous ligand which activates these receptors.

PMID- 1356797
TI  - Effects of alpha-adrenoceptor antagonists and clonidine on the haemodynamic
      response to acute hypovolaemia in conscious rabbits.
AB  - In conscious rabbits an inferior vena caval cuff was progressively inflated so
      cardiac output fell at a constant approximately 8% of its baseline value. There
      was a biphasic haemodynamic response, consisting of an initial compensatory phase
      during which there was progressive systemic vasoconstriction and tachycardia,
      followed by a decompensatory phase in which systemic vasoconstriction failed
      abruptly, blood pressure plummeted and heart rate declined. We tested the effects
      on the haemodynamic response of prior 4th ventricular, and in some cases
      intravenous, infusions of saline, yohimbine, clonidine, yohimbine plus clonidine,
      and bunazosin. From the results we conclude that a yohimbine-sensitive mechanism
      in the brainstem, possibly alpha 2-adrenoceptor-mediated, may be an essential
      element of the cardiac receptor-mediated decompensatory phase of acute central
      hypovolaemia, but does not contribute to the arterial baroreflex-mediated
      compensatory phase.

PMID- 1356798
TI  - Stimulation of bicarbonate secretion by atypical beta-receptor agonists in rat
      cecum in vitro.
AB  - This study examined the effects of beta-adrenoceptor agonists on bicarbonate
      secretion by the rat cecum in vitro. Isoprenaline, the beta 2-selective agonist
      salbutamol and the 'atypical' beta-agonist SR58611A stimulated bicarbonate
      secretion in a concentration related manner. Another atypical agonist, BRL 37344,
      also stimulated. Responses to isoprenaline were antagonised by alprenolol and
      propranolol (both 20 microM) but not the selective antagonists practolol (10
      microM) or ICI 1185511 (1 microM). Responses to SR 58611A were only antagonised
      by alprenolol. Replacement of Cl- by NO3- on the mucosal surface reduced basal
      secretion and abolished the response to isoprenaline. Exposure to a single
      concentration of atypical agonist resulted in desensitisation to a second
      application and to isoprenaline. There was no evidence of desensitisation with
      isoprenaline or salbutamol. The results show that beta-adrenoceptor agonists
      stimulated bicarbonate secretion in contrast to the previously described
      inhibitory effect of cholinergic drugs in this tissue. Stimulation was mediated
      by beta-adrenoreceptors, which had properties consistent with the atypical
      receptors described in gut smooth muscle and in adipose tissue. Both adrenergic
      and cholinergic drugs may act on the same mechanism of secretion which may
      involve an exchange of HCO3- for mucosal Cl-.

PMID- 1356799
TI  - Dose-dependent conditioned place preference produced by etonitazene and morphine.
AB  - The conditioned place preference (CPP) paradigm was used to study the reinforcing
      properties of etonitazene in comparison with those of morphine. Increasing doses
      of etonitazene (2.5-15 micrograms/kg i.p.) and morphine (1-80 mg/kg i.p.) induced
      a dose-dependent CPP. High doses of etonitazene (25-40 micrograms/kg) did not
      elicit CPP. In addition, these reinforcing properties were related to behavioral
      modifications such as analgesia, assessed with the tail-flick method, and
      increased catalepsy, evaluated by a scoring system. It is concluded that neither
      the strong behavioral effects induced by etonitazene nor tolerance to such
      effects account for the results. These findings are discussed with regard to the
      possibility that etonitazene could interfere with associative learning motivated
      by reward.

PMID- 1356800
TI  - Presynaptic inhibition by clonidine of neurotransmitter amino acid release in
      various brain regions.
AB  - The release of endogenous aspartic acid (Asp), glutamic acid (Glu) and gamma
      aminobutyric acid (GABA) was investigated in synaptosomes prepared from various
      regions of the rat brain. The basal release of Asp, Glu and GABA from various
      regions was 12-35, 24-107 and 15-43 pmol/min per mg protein, respectively.
      Exposure to a depolarizing concentration of KCl (30 mM) resulted in 1.7 to 3.6
      fold increases in Asp, Glu and GABA release. When clonidine (10(-4) M) was added
      to the perfusion medium, the K(+)-evoked overflow of both Asp and Glu was
      inhibited by 50-90% in the anterior cortex, thalamus and hypothalamus. Clonidine
      inhibited the K(+)-evoked Glu overflow by 30-40% in the posterior cortex and
      hippocampus. No significant effects were observed in the other brain regions
      (olfactory bulb, striatum, midbrain, cerebellum, pons, medulla oblongata). The
      inhibitory effects of clonidine were counteracted by an alpha 2-adrenoceptor
      antagonist, rauwolscine. The data suggest that the basal and K(+)-evoked release
      of Asp, Glu and GABA from nerve terminals is different in rat brain regions and
      that the presynaptic alpha 2-adrenoceptors which regulate the release of
      excitatory amino acids are mainly distributed in the anterior cerebral cortex,
      thalamus and hypothalamus of the rat brain.

PMID- 1356801
TI  - Behavioral effects of modulators of ATP-sensitive K+ channels in the rat dorsal
      pallidum.
AB  - The effects of the potent ATP-sensitive K+ channel blocker glipizide were
      measured on the locomotor activity of rats after bilateral intracerebral
      administration into the dorsal pallidum. Glipizide (10 pmol) was found to reduce
      spontaneous locomotor activity measured during the night cycle of the rats,
      whereas the ATP-sensitive K+ channel activator (-)-cromakalim (5 fmol) enhanced
      spontaneous locomotor activity. Glipizide (0.5, 2.5 and 10 pmol) was also found
      to depress noticeably d-amphetamine-induced locomotor activity (1 mg/kg s.c.).
      These results are in agreement with the idea that ATP-dependent potassium
      channels within the dorsal pallidum are involved in controlling motor activity in
      the rat.

PMID- 1356802
TI  - Effects of inhibitory and excitatory drugs on the metabolic rhythm of the hamster
      suprachiasmatic nucleus in vitro.
AB  - In order to elucidate the role of excitatory and inhibitory transmitters within
      the suprachiasmatic nucleus (SCN) in the circadian change of 2-deoxyglucose (2
      DG) uptake in this nucleus, the effects of 8-hydroxy-2-(di-n-propylamino)
      tetralin hydrobromide (8-OH-DPAT), muscimol, flurazepam, pentobarbital and
      glutamate on uptake of 2-DG by hamster SCN were examined in hypothalamic slice
      preparations. 2-DG uptake in the SCN was high during the subjective day and low
      during the subjective night. The high uptake of 2-DG in the SCN during the
      daytime was inhibited by the superfusion of 8-OH-DPAT, muscimol, flurazepam and
      pentobarbital in a dose-dependent manner, but the low uptake of 2-DG during the
      night was unaffected. The low uptake during the night was significantly increased
      by treatment with glutamate, whereas 2-DG uptake during the day was unaffected.
      In contrast to the above results, 20 mM KCl and 1 microM tetrodotoxin increased
      and decreased 2-DG uptake during both the day and night, respectively. The
      present results strongly suggest that agonists of 5-HT1A receptors and GABAA
      benzodiazepine-barbiturate complex receptors regulate the function of the SCN
      through their inhibitory action on 2-DG uptake during the day, and that glutamate
      also regulates SCN function through it stimulatory action on 2-DG uptake during
      the night.

PMID- 1356803
TI  - Involvement of serotonin receptors in methionine sulfoximine-induced hypothermia
      in the rat.
AB  - L-Methionine-D,L-sulfoximine (MSO), intraperitoneally (i.p.) or
      intracerebroventricularly (i.c.v.) (third ventricle) injected at a convulsant
      dose, induced a centrally mediated body hypothermia in the restrained rat
      maintained at an ambient temperature of 23 degrees C. Pretreatment with (+/-)
      pindolol (1.5-3 mg/kg s.c.) significantly attenuated MSO-induced hypothermia, but
      at a dose of 6 mg/kg s.c. hypothermia developed without any modification of its
      characteristics. Pretreatment with (-)-propranolol (16-25 mg/kg i.p.) potentiated
      MSO-induced hypothermia, but pretreatment of MSO-treated rats with ketanserin
      (0.7-4 mg/kg i.p.) did not significantly modify hypothermia. Selective
      antagonists for beta-adrenoceptors were used and their effects on MSO-induced
      hypothermia were compared with those of pindolol and propranolol. Pretreatment
      with betaxolol (1.5-4 mg/kg s.c.) did not modify the hypothermia following
      administration of MSO, but potentiation of hypothermia was recorded in rats
      pretreated with ICI 118,551 (2.26 mg/kg i.p.) then i.p. injected with MSO. These
      findings favour a control exerted by 5-HT1 receptors in the central development
      of MSO-induced hypothermia in the restrained rat.

PMID- 1356804
TI  - Alpha 2-adrenoceptor and catecholamine-insensitive binding sites for
      [3H]rilmenidine in membranes from rat cerebral cortex.
AB  - The kinetic and pharmacological characteristics of the binding of the oxazoline
      antihypertensive drug, [3H]rilmenidine, to membranes of rat cerebral cortex have
      been determined. Computerised resolution of curvi-linear, equilibrium binding
      isotherms was consistent with the existence of two distinct binding sites for
      [3H]rilmenidine: Kd 17.3 +/- 7.41 nM, Bmax 0.197 +/- 0.06 pmol/mg protein and Kd
      254 +/- 48 nM, Bmax 1.59 +/- 0.08 pmol/mg protein. Moreover, the resolution of
      two association and dissociation rates also suggested the existence of two
      binding site populations. Drug inhibition studies revealed that specific binding
      of [3H]rilmenidine (2 nM) was only inhibited by a maximum of 50% by the
      catecholamines, adrenaline and noradrenaline, but was completely inhibited by
      some oxazolines, by guanabenz (a guanidino drug) and by several imidazoline
      compounds including naphazoline, oxymetazoline and clonidine. Binding isotherms
      for these drugs were also best fit by a two-site model. The relative Ki values at
      the high affinity site for [3H]rilmenidine and the number of these high affinity
      sites are consistent with this site being an alpha 2-adrenoceptor. The high
      affinity of oxymetazoline and low affinity of prazosin for high affinity
      [3H]rilmenidine binding sites together with the rank order of potency of
      oxymetazoline greater than phentolamine greater than SKF 104078 greater than ARC
      239 greater than prazosin suggest that [3H]rilmenidine binds to the alpha 2A sub
      type of adrenoceptor. Computer-resolved Ki values for drugs at the larger number
      of lower affinity binding sites were very similar to Ki values determined in the
      presence of 10 microM adrenaline (used to block alpha 2-adrenoceptor
      binding).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356805
TI  - Thiokynurenates prevent excitotoxic neuronal death in vitro and in vivo by acting
      as glycine antagonists and as inhibitors of lipid peroxidation.
AB  - Several derivatives of kynurenic and thiokynurenic acids were synthesized and
      tested for their ability to protect primary cultures of cerebellar granule cells
      against excitotoxic damage, and to affect the binding of [3H]glycine ([3H]Gly),
      [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA), [3H]3-(2
      carboxypiperazine-4-yl-)propyl-1-phosphonic acid ([3H]CPP), [3H]kainic acid and
      [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) to rat cortical
      membranes. Kynurenic and thiokynurenic acid derivatives with one or two halogens
      in position 5 or 7 were selective glycine antagonists, failing to affect N-methyl
      D-aspartate (NMDA), kainate or AMPA sites at micromolar concentrations. 7-Cl
      kynurenic, 7-Cl-thiokynurenic, 5,7-diCl-kynurenic and 5,7-diCl-thiokynurenic
      acids had similar IC50s for displacing [3H]Gly from its strychnine-insensitive
      site and for reducing the stimulated (0.5 microM NMDA and 1 microM glycine)
      [3H]TCP binding to cortical membranes. However, 7-Cl-thiokynurenic acid was
      particularly potent to prevent excitotoxic neuronal death in cultured cerebellar
      granule cells. This action may be ascribed to inhibition of lipid peroxidation, a
      property which was demonstrated for the 5- or 7-Cl derivatives of thiokynurenic
      acid. Furthermore, 7-Cl-thiokynurenic acid reduced excitotoxic damage caused by
      the injection of quinolinic acid in the rat striatum. Thus, 7-Cl-thiokynurenic
      acid appears to be a new compound with interesting antiexcitotoxic properties
      both in vitro and in vivo.

PMID- 1356806
TI  - The interaction of R(+)- and S(-)-zacopride with PCPA to modify rodent aversive
      behaviour.
AB  - The interaction of R(+)- and S(-)zacopride (0.00001-10 mg/kg i.p.) with
      parachlorophenylalanine (PCPA, 3 day treatment 100 mg/kg i.p.) to modify
      behaviour in an aversive situation was investigated in the mouse black and white
      test box and rat social interaction test. R(+)-Zacopride (but not S(-)zacopride)
      and PCPA had an anxiolytic profile of action to reduce aversive responding in
      both species. Their established anxiolytic profiles were abolished by a
      subsequent treatment with S(-)zacopride. In contrast, S(-)-zacopride was less or
      ineffective if administered simultaneously with R(+)-zacopride. A co-treatment of
      PCPA with R(+)-zacopride also inhibited the anxiolytic profiles observed to the
      individual treatments. It is concluded that there is a complex interaction
      between the isomers of zacopride to modify responding to an aversive situation
      that is dependent on the temporal sequence of drug administration, and which may
      be modified by changes in basal 5-hydroxytryptamine (5-HT) tone and agonist,
      partial agonist and antagonist effects at the 5-HT3 receptor.

PMID- 1356807
TI  - Profiles of interaction of R(+)/S(-)-zacopride and anxiolytic agents in a mouse
      model.
AB  - The mouse black and white test box was used to measure changes in behaviour in an
      aversive situation where the administration of R(+)-zacopride (but not S(-)
      zacopride) alone decreased aversive responding to the white area. A similar
      anxiolytic profile of action was observed using parachlorophenylalanine (PCPA),
      whose effects were antagonised by a co-treatment with R(+)-zacopride and reversed
      by S(-)-zacopride to an exacerbation of the aversive response. An anxiolytic
      profile of action was also observed using ondansetron, granisetron,
      chlordiazepoxide, diazepam, ritanserin, 8-OH-DPAT (8-hydroxy-2-(di-n
      propylamino)tetralin), E4424 (2-[4-[4-(4-chloro-l-pyrazoyl)butyl]-l-piperazinyl]
      pyrimidine), umepsirone, DuP753 (2-n-butyl-4-chloro-5-hydroxy-methyl-1-[2(1H
      tetrazol-5-yl) biphenyl-4-yl)methyl)]-imidazole), SQ29,852 ((S)-1-[6-amino
      2[hydroxy)(4-phenyl-butyl)phosphinyl]-oxy)-1- nexy]-2-proline), devazepide and
      guanfacine, and this was retained following co-treatment with PCPA. The
      anxiolytic profile of action of PCPA was also retained following co-treatment
      with renzapride which when administered alone failed to modify behaviour.
      However, the ability of chlordiazepoxide, diazepam, ondansetron and E4424 (but
      not devazepide, DuP753 or SQ29,852) to reduce aversive responding was inhibited
      by co-treatment with R(+) and/or S(-)-zacopride. It is concluded that the
      reduction in aversive responding caused by pharmacological manipulation at the
      benzodiazepine, 5-HT receptor subtypes 5-HT1A, 5-HT1C/5-HT2 and 5-HT3 (but not at
      the cholecystokin CCKA or angiotensin receptors or inhibition of angiotensin
      converting enzyme) can be inhibited by R(+) and S(-)-zacopride. The data is
      discussed in terms of zacopride having an agonist or partial agonist effect at
      the 5-HT3 receptor.

PMID- 1356808
TI  - NMDA receptor-mediated depolarizing action of proline on CA1 pyramidal cells.
AB  - This study investigated the actions of proline on CA1 hippocampal pyramidal cells
      with use of slice preparations. Bath-applied L-proline first induced these cells
      to fire multiple orthodromic population spikes in response to a single stimulus
      and then blocked their response to both orthodromic and antidromic stimulation.
      These effects could be explained by postsynaptic depolarization followed by
      depolarization block. Grease-gap studies confirmed that L-proline depolarizes CA1
      pyramidal cells. D-Proline was inactive in these tests. Excitatory amino acid
      antagonists reduced depolarizing responses to proline and N-methyl-D-aspartate
      (NMDA) in parallel. Mn2+ failed to attenuate proline-evoked depolarizations at
      concentrations that substantially inhibited synaptic transmission, but at a
      higher concentration it reduced responses to both proline and NMDA. These results
      suggest that proline depolarized CA1 pyramidal cells mainly by activating
      postsynaptic NMDA receptors. The neuroexcitatory and neurotoxic actions of
      proline in the hippocampus may contribute to the seizures and mental retardation
      associated with hyperprolinemia.

PMID- 1356809
TI  - Effects of cortical ablation on apomorphine- and scopolamine-induced changes in
      dopamine turnover and ascorbic acid catabolism in the rat striatum.
AB  - Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid
      and dehydroascorbic acid (DHAA) were measured by HPLC in the striatum of rats
      whose fronto-parietal cortex had been unilaterally ablated after a single
      injection of apomorphine (1 mg/kg s.c.), scopolamine (0.6 mg/kg s.c.) or L
      glutamate (500 mg/kg i.p.). Unilateral cortical ablation decreased striatal
      levels of glutamate in both striata ipsilateral (35%) and contralateral (17-25%)
      to the lesion. Apomorphine and scopolamine significantly increased (+94 and
      +122%, respectively) the DHAA/ascorbic acid ratio in the striata ipsilateral to
      the lesion in unoperated and sham-operated rats (+72 and +34%, respectively), but
      both drugs failed to increase it in ablated rats. L-Glutamate significantly
      increased the DHAA/ascorbic acid ratio in unoperated (+53%) and ablated rats
      (+37%). The increase in sham-operated rats (+34%) did not reach statistical
      significance. Apomorphine and scopolamine significantly decreased the DOPAC/DA
      ratio in the striata ipsilateral to the lesion of unoperated, sham-operated and
      ablated rats. The decrease in the DOPAC/DA ratio induced by apomorphine and
      scopolamine was greater in ablated rats than in sham-operated rats. L-Glutamate
      induced only minor changes in striatal DA and DOPAC levels. We conclude that the
      apomorphine- and scopolamine-induced increase in ascorbic acid oxidation in the
      striatum requires intact cortico-striatal glutamatergic pathways. Cortical
      ablation potentiates the apomorphine- and scopolamine-induced inhibition of
      striatal DA turnover.

PMID- 1356810
TI  - [125I]thienylphencyclidine, a novel ligand for the NMDA receptor.
AB  - We have monitored the binding of [125I]thienylphencyclidine ([125I]TCP), a novel
      high affinity radioiodinated ligand that specifically recognizes the NMDA (N
      methyl-D-aspartate) receptor in rat brain membranes. [125I]TCP binds with an
      affinity of about 30 nM, and recognizes a similar number of binding sites to
      previously employed ligands for this receptor. [125I]TCP binding is characterized
      by slow association and dissociation rates, and the latter can be modified by the
      addition of Mg2+ or Zn2+, as previously described for [3H]dizocilpine
      ([3H]MK801). Other phencyclidine-like ligands displaced [125I]TCP binding with
      the order of potency dizocilpine greater than thienylphencyclidine greater than
      ITCP greater than phencyclidine greater than ketamine. The binding of [125I]TCP
      was also increased by NMDA and glycine-site agonists and inhibited by antagonists
      of these sites. Surprisingly, however, the polyamines spermidine and spermine did
      not increase [125I]TCP, even though the polyamine antagonist arcaine was an
      effective inhibitor of binding. These results show that [125I]TCP is a useful
      ligand for the NMDA receptor complex that binds to the receptor in a manner that
      is qualitatively distinct from previously described ligands.

PMID- 1356811
TI  - Demonstration of inhibition of cyclic AMP accumulation in brain by very low
      concentrations of lithium in the presence of alpha-adrenoceptor blockade.
AB  - In the present paper, we have studied the effect of lithium on cAMP levels
      induced by isoprenaline and norepinephrine in the presence of alpha- or beta
      adrenoceptor antagonists. Our results show that low lithium concentrations,
      starting at 0.3 x 10(-3) M, have a significant inhibitory effect on cAMP content
      induced by isoprenaline in brain tissue pretreated with the alpha-adrenoceptor
      blocker phenoxybenzamine. On the other hand, the inhibitory effect of lithium on
      cAMP levels induced by norepinephrine when beta-adrenoceptors are blocked with
      propranolol, is observed at concentrations starting at 2.5 x 10(-3) M. These
      results show that in the presence of alpha blockade, low lithium concentrations
      which are within the therapeutic plasma range for treatment of manic patients,
      are able to act on an adenylate cyclase-cAMP system coupled to beta
      adrenoceptors.

PMID- 1356812
TI  - Developmental changes in the effect of atrial natriuretic peptide on tissue
      cyclic GMP content and particulate guanylate cyclase activity of aorta, kidney
      and lung of rats.
AB  - To investigate possible developmental changes in the physiological effect of
      atrial natriuretic peptide (ANP) after birth, we studied the effect of ANP on the
      slice cGMP content and the particulate guanylate cyclase activity of aorta,
      kidney and lung in neonate, 2-week-old and adult rats of both sexes. Incubation
      with human ANP(99-126) (hANP) increased significantly the slice cGMP content of
      aorta, kidney and lung in three ages of rats. The hANP-stimulated fraction of
      cGMP contents of kidney decreased, that of lung increased with development,
      whereas that of aorta showed no significant change. Consistently, the hANP
      responsive particulate guanylate cyclase activity decreased in kidney, increased
      in lung during development, without significant developmental change in aorta.
      These results indicate a differential change in the effect of hANP on the slice
      cGMP content among tissues during development. The developmental change in the
      effect of hANP on slice cGMP content is probably caused by the ontogenetic change
      in activation of ANP receptor-linked guanylate cyclase.

PMID- 1356813
TI  - A toxin (Aga-GI) from the venom of the spider Agelenopsis aperta inhibits the
      mammalian presynaptic Ca2+ channel coupled to glutamate exocytosis.
AB  - Venom of the funnel web spider Agelenopsis aperta was fractionated and screened
      for activity against the mammalian presynaptic, voltage-dependent Ca2+ channel
      coupled to glutamate exocytosis. A purified toxin (Aga-GI) from this venom
      inhibits glutamate exocytosis evoked by elevated potassium or by 4-aminopyridine
      but is without effect on ionomycin-evoked release. At the same time a partial
      inhibition of the depolarisation-evoked elevation of cytoplasmic free Ca2+ is
      seen. The toxin does not inhibit 4-aminopyridine- or potassium-evoked
      depolarisation, or block Ca(2+)-dependent, potassium-evoked [3H]noradrenaline
      release. The results indicate that the venom contains a toxin capable of
      inhibiting the presynaptic voltage-dependent Ca2+ channel coupled to glutamate
      exocytosis in the mammalian central nervous system. This channel is resistant to
      block by either omega-conotoxin GVIA or nifedipine. Thus Aga-GI is a novel tool
      with which to probe this elusive neuronal calcium channel.

PMID- 1356815
TI  - Stimulation of cyclic AMP production in human alveolar macrophages induced by
      inflammatory mediators and beta-sympathicomimetics.
AB  - We have investigated the effects of inflammatory mediators and beta-adrenoceptor
      agonists on the adenylyl cyclase responsiveness in alveolar macrophages from
      control subjects, patients suffering from chronic obstructive pulmonary disease
      (COPD) and asthmatics. Basal cyclic AMP (cAMP) levels in alveolar macrophages
      from COPD patients were significantly elevated (plus 42%) as compared to
      controls. In addition, the adenylyl cyclase responsiveness to prostaglandin E2,
      histamine and the beta-adrenoceptor agonist salbutamol was significantly impaired
      in alveolar macrophages from COPD patients and asthmatics. The lipid mediator
      platelet activating factor showed no effect on cAMP production in all three
      alveolar macrophage populations. Furthermore, the cAMP-enhancing effects of
      isoprenaline, salbutamol and histamine appeared to be mediated via beta 2
      adrenoceptors and histamine H2-receptor subtypes respectively. Taken together,
      these data suggest an intrinsic desensitization phenomenon in alveolar
      macrophages from COPD patients and asthmatics.

PMID- 1356814
TI  - The neuroprotective properties of ifenprodil, a novel NMDA receptor antagonist,
      in neuronal cell culture toxicity studies.
AB  - We investigated the effect of ifenprodil on excitotoxic cell death induced by
      acute exposure to glutamate receptor agonists in primary cultures of foetal mouse
      cerebral cortex. L-Glutamate and N-methyl-D-aspartate (NMDA) but not kainate and
      quisqualate-induced toxicity was attenuated in the presence of ifenprodil. In
      addition, ifenprodil and MK-801 blocked NaCN-induced toxicity. It is concluded
      that the cerebro-protective properties of ifenprodil in these models are mediated
      by NMDA receptor antagonism.

PMID- 1356816
TI  - Cyanide selectively augments kainate- but not NMDA-induced release of glutamate
      and taurine.
AB  - The effect of cyanide on the kainate-, quisqualate- and N-methyl-D-aspartate
      (NMDA)-induced release of several amino acids from cerebellar granule neurons was
      studied. Cyanide, 100 microM, augmented the kainate- and quisqualate-induced
      release of glutamate and taurine in neurons but had no effect on the NMDA-induced
      release of these excitatory amino acids. In addition to the interaction with the
      above excitatory amino acids, cyanide had effects on several amino acids
      independent of excitatory amino acid stimulation; cyanide treatment resulted in a
      significant elevation over saline controls of arginine and taurine, but not
      alanine, aspartate+asparagine or glycine. With the exception of taurine, this
      pattern was not apparent in cells treated with any of the above excitatory amino
      acid.

PMID- 1356817
TI  - Surface distribution and internalization of erbB-2 proteins.
AB  - We report the localization over the cell surface and the early steps of antibody
      induced internalization of the product of the erbB-2 proto-oncogene, structurally
      related to the epidermal growth factor receptor (EGFR). We show that erbB-2/p 185
      is mostly excluded from endocytic pits on the cell surface. Incubation at 37
      degrees C with an anti-erbB-2/p185 monoclonal antibody induces the rapid entry of
      the protein into the cell. Similar internalization is shown by a chimeric
      molecule EGFR/erbB-2 in response to EGF. Both the timing and the pathway of
      internalization followed by the erbB-2/p185 appear totally similar to those
      described for the EGFR. At variance with the normal erbB-2/p185, two mutant
      activated erbB-2 proteins are frequently localized within endocytic pits of the
      cell surface, indicating that mutations in the transmembrane regions may
      determine constitutive internalization of the protein.

PMID- 1356818
TI  - Regulation of transglutaminase 1 gene expression by 12-O-tetradecanoylphorbol-13
      acetate, dexamethasone, and retinoic acid in cultured human keratinocytes.
AB  - Transglutaminase 1 (TG1) is an enzyme that is expressed at the late stage of
      terminal differentiation of keratinocytes and catalyzes the epsilon-(gamma
      glutamyl)lysine cross-linking reaction to form a highly insoluble cell envelope.
      To elucidate the mechanism of TG1 gene expression in keratinocytes, we examined
      the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), dexamethasone, 1,25
      dihydroxyvitamin D3, and retinoic acid on the levels of TG1 mRNA in cultured
      normal human epidermal keratinocytes (NHEK). Treatment of NHEK with TPA, up to 10
      nM, markedly increased the levels of TG1 mRNA in a dose-dependent manner. The
      effect by treatment with 1 nM TPA reached a peak after 16 h of incubation (20
      fold above the basal level). In contrast, phorbol had no effect on TG1 gene
      expression. The induction of TG1 mRNA expression by TPA was inhibited by 1-(5
      isoquinolinylsulfonyl)-2-methyl-piperazine (H-7) and staurosporine. Dexamethasone
      at a concentration of 1 microM also increased the TG1 mRNA levels, but the
      maximum induction was observed (3-fold above the basal level) after 72 h of
      incubation. The effect of dexamethasone was not suppressed by H-7. Moreover, 1
      microM of retinoic acid completely inhibited the induction of TG1 mRNA by both
      TPA and dexamethasone. 1,25-Dihydroxyvitamin D3 showed no effect on the TG1 mRNA
      levels. From these results, we suggest that the expression of TG1 gene may be
      upregulated by protein kinase C and glucocorticoid receptor systems and down
      regulated by the retinoic acid receptor system.

PMID- 1356819
TI  - Intracellular distribution of a nuclear localization signal binding protein.
AB  - The transport of proteins into the nucleus requires the recognition of a nuclear
      localization signal sequence. Several proteins that interact with these sequences
      have been identified, including one of about 66 kDa. We have prepared antibodies
      that recognize the 66-kDa nuclear localization signal binding protein (NLSBP) and
      inhibit nuclear localization in vitro. By immunofluorescence, it is seen that the
      NLSBP is predominantly cytoplasmic and is distributed peripherally around the
      nucleus and the microtubule organizing center. There is also a weak punctate
      staining of the surface of the nucleus. Methanol-fixed cells can also be stained
      directly with fluorescently labeled karyophilic proteins. These stains reveal the
      same cytoplasmic structures as anti-NLSBP. The expression of the NLSBP is growth
      dependent. When cells grown to confluence are examined, the cytoplasmic staining
      is greatly reduced, leaving the punctate nuclear staining as the predominant
      feature. In serum-starved cells, very little staining of either the cytoplasm or
      the nucleus can be seen. Upon simulation by the addition of serum, the original
      cytoplasmic and nuclear envelope staining is restored. Cells grown in the
      presence of colchicine or taxol have an altered NLSBP distribution but apparently
      normal cytoplasmic nuclear transport.

PMID- 1356820
TI  - Phylogenetic and epidemiological analysis of Neisseria meningitidis using DNA
      probes.
AB  - The genetic relationships between various serotypes and serogroups of
      meningococcal strains were investigated by restriction fragment-length
      polymorphism (RFLP) analysis using a number of random DNA probes and a probe
      containing a truncated copy of the meningococcal insertion sequence IS1106. The
      data were used to estimate genetic distance between all pairs of strains and to
      construct phylogenetic trees for meningococcal strains. B15:P1.16R strains
      isolated from cases of systemic meningococcal disease in two health districts
      with a high incidence of disease were clonal in contrast to similar strains from
      cases occurring in other parts of the UK. Strains from these areas, which contain
      a similar genomic deletion, were found to be derived from two distinct lineages
      within the B15:P1.16R phylogenetic group. RFLP data demonstrated that present
      serological typing systems for the meningococcus do not necessarily reflect true
      genetic relationships.

PMID- 1356822
TI  - Inhibition of ocular gamma glutamyl transpeptidase by acetazolamide.

PMID- 1356823
TI  - Proceedings of the X International Congress of Eye Research. Stresa, Italy,
      September 20-25, 1992. Abstracts.

PMID- 1356821
TI  - Molecular epidemiology of Shigella infections in Israel.
AB  - The DNAs of Shigella sonnei or Shigella dysenteriae type 1 strains isolated in
      outbreaks of shigellosis or in sporadic cases were analysed by restriction
      fragment length polymorphism (RFLP). Southern blots of the DNAs of 36 S. sonnei
      isolates digested by 8 restriction enzymes were hybridized with an Escherichia
      coli rRNA probe. The S. sonnei strains were unexpectedly diverse in their RFLP.
      Antibiotypes of the same isolates showed clusters of strains corresponding to the
      various outbreaks. On the other hand, RFLP analysis suggested concomitant
      multiple sources of infection rather than a common source and thereby introduced
      a new insight in the epidemiology of shigellosis. RFLP was also used to trace S.
      dysenteriae type 1 transmission in a recent cluster of clinical cases. Although
      antibiotic resistance patterns indicated the presence of more than one strain,
      RFLP analysis showed that the six isolates were identical clones and suggested
      the loss of an R episome after one person-to-person passage.

PMID- 1356826
TI  - Aberrations in cerebral vascular functions due to Plasmodium yoelii nigeriensis
      infection in mice.
AB  - Plasmodium yoelii nigeriensis infection in mice caused an increase in uptake of
      125I-labeled bovine serum albumin, 51Cr-labeled erythrocytes and Evans blue dye
      from peripheral circulation into the brain. Isolated cerebral microvessels which
      were characterized in terms of their morphology under scanning electron
      microscope and enhancement of the specific activities of biochemical markers,
      viz. alkaline phosphatase, gamma-glutamyl transpeptidase, and monoamine oxidase,
      showed significant decrease in these activities due to P. yoelii nigeriensis
      infection. On the other hand, relatively minor (statistically insignificant)
      changes occurred in the first two enzyme specific activities in the cerebral
      cortex and monoamine oxidase registered an increase in this tissue due to
      infection. Histological examination of the cerebral tissue of infected animals by
      light and electron microscopy showed broken blood vessel walls and leakage of
      erythrocytes into extravascular space, some of which contained intraerythrocytic
      malarial parasite in a state of cell division.

PMID- 1356825
TI  - Antifungal properties of taxol and various analogues.
AB  - The antimitotic agent taxol was tested for toxicity towards fungi from different
      taxonomic groups and found to be particularly active against oomycete fungi. In
      germinating zoospore cysts of the oomycete Phytophthora capsici the mechanism of
      action of taxol was shown to involve inhibition of mitosis, presumably resulting
      from an effect on microtubules. Various taxol analogues with deleted A-ring C-13
      side chain substituents were tested for toxicity towards P. capsici and
      Aphanomyces cochlioides to provide insight into structural features required for
      activity. The importance of the side chain was shown by the much lower activity
      as compared to taxol of analogues lacking all or part of the side chain. The
      effect of stereochemistry at the C-2' position on fungitoxicity towards oomycetes
      was similar to that reported previously on mammalian microtubule assembly.

PMID- 1356824
TI  - Control of the cardiovascular system of Aplysia by identified neurons.
AB  - The neural network that controls the cardiovascular system of Aplysia adapts
      cardiovascular function to a variety of different physiological and behavioral
      situations. It (1) coordinates the cardiovascular system with the renal and
      respiratory systems; (2) modifies both systemic and regional blood flow during
      food-elicited arousal and feeding; and (3) changes the tension of longitudinal
      vascular muscle to adapt the arterial tree to changes in body shape. Indirect
      evidence suggests that the cardiovascular control circuit may also play a role in
      maintaining homeostasis during egg laying. Several putative neurotransmitters,
      including acetylcholine, serotonin, R15 alpha 1 and R15 alpha 2 peptides, have
      been localized to identified neurons in this circuit.

PMID- 1356827
TI  - The secretion of aspartyl proteinase, a virulence enzyme, by isolates of Candida
      albicans from the oral cavity of HIV-infected subjects.
AB  - Prevalence, serotype and in vitro secretion of aspartyl proteinase, a virulence
      enzyme, were studied in Candida isolates from the oral cavity of 337 HIV-infected
      subjects. Controls were 95 age-sex-matched HIV- (seronegative) subjects,
      belonging to either HIV-risk categories (47) or to the normal, general population
      (48). Fungi were isolated from 155 HIV+ subjects. C. albicans was the most
      prevalent species (85.8% of all isolates). 94.6% of C. albicans isolates were
      serotype A and all were agglutinated by a monoclonal antibody (AF1) directed
      against a major mannoprotein immunogen of the candidal cell wall, confirming
      previous results with C. albicans isolates from non-immunodeficient subjects.
      With regard to the stage of HIV infection, there were no statistically
      significant differences in the incidence of oral Candida carriage between
      asymptomatic (stage II) HIV+ and HIV- subjects, and between stage II and
      lymphadenopathic (stage III) individuals. Also, the low (3.8%) incidence of oral
      candidiasis in the subjects of the latter stage was insignificant with respect to
      stage II subjects. However, the incidence of C. albicans in stage IV (AIDS)
      subjects (46.8%) was significantly higher than in all other subjects, and in
      almost all cases, fungal isolation was accompanied by oral thrush and lower CD4+
      lymphocyte counts (less than 400 x 10(6)/L). All isolates of C. albicans were
      proteolytic in vitro, as assessed by scoring the proteinase activity on BSA agar
      and monitoring the secreted proteinase antigen by a highly sensitive (1 ng) and
      specific immunoenzymatic assay.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356828
TI  - Antigen-specific cytolysis of infected cells in murine candidiasis.
AB  - Immune L3T4+ and Lyt-2+ lymphocytes play an important role in the acquired
      resistance of mice to challenge with virulent Candida albicans, and release
      macrophage-activating cytokines in response to yeast cells in vitro. To determine
      whether antigen (Ag)-specific cytotoxic T lymphocytes are generated during fungal
      infection, purified L3T4+ and Lyt-2+ lymphocytes from immunized mice were
      cultured in the presence of syngeneic accessory cells, Candida Ag, and IL-2.
      Yeast-infected bone marrow macrophages and peritoneal exudate neutrophils were
      used as target cells in a standard 51Cr release assay. Ag-specific, MHC
      unrestricted lysis of infected macrophages was evident with immune Lyt-2+ cells
      after 5-10 days in culture. Under the same experimental conditions, the cytotoxic
      activity of L3T4+ cells was negligible, but its expression could be induced by
      the addition of anti-CD3 antibody. Culturing immune Lyt-2+ cells for shorter
      periods of time (1-2 days) resulted in preferential lysis of infected
      neutrophils. In addition, at limiting effector cell numbers, Ag-specific MHC
      restricted lymphocytes with cytotoxic activity to infected macrophages could be
      identified. We suggest that C. albicans infection stimulates multiple cytotoxic T
      cell precursors with varying recognition stringency, which may have an important
      role in antifungal resistance in vivo.

PMID- 1356829
TI  - Inhibition of hormone-sensitive lipase by intermediary lipid metabolites.
AB  - Hormone-sensitive lipase (HSL) is inhibited in a non-competitive manner by oleoyl
      CoA, oleic acid and 2-monopalmitoylglycerol, 50% inhibition being observed at
      concentrations of approx. 0.1 microM, 0.5 microM and 500 microM, respectively.
      HSL is a key enzyme in lipid metabolism, mobilising triacylglycerol and
      cholesterol ester stores in several tissues. Feedback inhibition of HSL by oleoyl
      CoA and oleic acid may therefore prevent accumulation of free fatty acids and
      cholesterol in the cell, whereas 2-monoacylglycerol may act as a feedback
      inhibitor if the capacity of monoacylglycerol lipase is exceeded.

PMID- 1356830
TI  - Crystallization of the cpn60/cpn10 complex ('holo-chaperonin') from Thermus
      thermophilus.
AB  - A stable complex of the chaperonins, cpn60 and cpn10 (Escherichia coli GroEL and
      GroES homologues), from the extremely thermophilic bacterium Thermus thermophilus
      has been isolated and crystallized. The crystals have dimensions up to 30 x 200 x
      200 microns. Ultra-thin sections of the crystals estimated by electron microscopy
      showed a rectangular lattice with unit cell parameters of a = 17 nm, b = 27 nm,
      gamma = 90 degrees.

PMID- 1356831
TI  - Cell cycle kinetics, tissue transglutaminase and programmed cell death
      (apoptosis).
AB  - Studies were undertaken on a highly metastatic hamster fibrosarcoma cell line
      with a view to assessing whether cells entering into apoptosis, measured by
      counting the number of transglutaminase mediated detergent insoluble envelopes,
      has any synchrony with a particular phase of the cell cycle. A double exposure of
      thymidine was used to block cells in early S-phase. Flow cytometry in combination
      with [3H]thymidine incorporation into DNA was used to assess the degree of
      synchrony and progression through the different phases of cell cycle. The
      apoptotic index was found to be at its maximum in mid-S-phase. Measurement of
      transglutaminase activity in each phase of the cell cycle indicated that the
      specific activity was also at its greatest during mid S-phase. The level of
      enzyme was relatively unchanged throughout the cell cycle indicating that the
      regulation of transglutaminase activity occurs primarily through effects on
      catalytic activity rather than enzyme synthesis.

PMID- 1356832
TI  - Isolation, sequencing and expression in E. coli of the urocanase gene from white
      clover (Trifolium repens).
AB  - The urocanase gene was detected in a clone obtained from a genomic library of
      white clover. The entire gene has been sequenced and expressed in the pT7-7/E.
      coli BL 21 (DE 3) system. The deduced sequence of the plant urocanase is 72%
      homologous with that of the well-characterized urocanase from Pseudomonas putida.
      The purification procedure, as well as kinetic and electrophoretic behaviour, of
      the new enzyme are described.

PMID- 1356833
TI  - N-acetylaspartylglutamate acts as an agonist upon homomeric NMDA receptor
      (NMDAR1) expressed in Xenopus oocytes.
AB  - The electrophysiological effects of N-acetylaspartylglutamate (NAAG), an
      endogenous peptide restrictively distributed in the central nervous system, were
      studied using Xenopus oocytes injected with RNAs transcribed from cloned
      glutamate receptor cDNAs. NAAG induced an inward current, dose dependently, in
      oocytes injected with RNA for an N-methyl-D-aspartate receptor subunit (NMDAR1).
      In contrast, the oocytes injected with RNAs for AMPA-selective glutamate
      receptors (GluR1, GluR3, GluR1+GluR2 and GluR2+GluR3) scarcely responded to NAAG,
      and the oocytes injected with RNA for kainate receptor (GluR6) did not respond to
      NAAG. The half-maximal response (ED50) value of NAAG on expressed NMDAR1 was 185
      microM, which shows that NAAG is about 115-times less potent than L-glutamate
      (Glu), the ED50 of which value was 1.6 microM. The maximal current amplitude
      induced by NAAG was about 70% of that by Glu. NAAG-induced current in NMDAR1
      injected oocytes was potentiated by glycine, dose-dependently antagonized by DL-2
      amino-5-phosphonovaleric acid, and blocked by magnesium ions in a voltage
      dependent fashion. These results suggest that NAAG is one of the endogenous
      agonists selective for NMDAR1.

PMID- 1356834
TI  - Transluminal angioplasty of the aorta, renal and mesenteric arteries in Takayasu
      arteritis: report of two cases.
AB  - Two patients with Takayasu arteritis presented with either severe renovascular
      hypertension or profound weight loss due to intestinal angina. The leading
      clinical signs were cured by successful percutaneous transluminal angioplasty
      (PTA) of the abdominal aorta and renal arteries in one patient and of the
      superior mesenteric artery and coeliac trunk in the second. These results and a
      literature review of the topic suggest that PTA should be the first therapeutic
      approach in symptomatic arterial stenoses due to TA in the inactive stage of the
      disease.

PMID- 1356835
TI  - [Proceedings of the 65th Congress of the Japan Endocrine Society. Kyoto, Japan,
      October 12-13, 1992. Abstracts].

PMID- 1356836
TI  - Margin configuration, die spacers, fitting of retainers/crowns, and soldering.
AB  - This article focuses on different margin configurations and the criteria they
      must meet to be considered clinically successful. In addition, the use of die
      spacers to lessen the cement film thickness to achieve a better marginal
      adaptation of cast restorations is presented. Also, the article presents a step
      by step method for fitting crowns or retainers in the laboratory and in a
      clinical setting to make this important procedure less time consuming, more
      precise, and easy to finalize. Finally, soldering in dentistry and the criteria
      required for its successful execution are discussed.

PMID- 1356837
TI  - Different effects of growth hormone-releasing hormone (GRH) and somatostatin on
      growth hormone and stable metabolite of prostaglandin E2, 13, 14-dihydro-15-keto
      prostaglandin E2 (PGE2-M) in normal subjects.
AB  - Twenty four healthy subjects were placed in two treatment groups: 1. The first
      group consisted of twelve subjects in whom growth releasing hormone (GRH) (1
      microgram/kg.BW) resulted in a marked and sustained elevation of serum growth
      hormone (GH) and a slight and delayed increase in plasma prostaglandin E2-M. In
      the second group, consisting also of twelve subjects, somatostatin infusion (500
      micrograms/250 ml) was initiated and maintained for 60 min. Serum GH
      significantly decreased at 30 and 60 min during infusion and 15 min thereafter.
      We did not observe any changes in plasma prostaglandin E2-M during or after
      somatostatin infusion. The results obtained confirm previous in vitro studies and
      suggest a possible link between growth releasing hormone and prostaglandin E2 in
      their action on growth hormone secretion. It seems that somatostatin does not
      play a role in the control of prostaglandin E2 release.

PMID- 1356838
TI  - [DNA polymorphisms].

PMID- 1356839
TI  - Pelvic surgery, reproductive factors and risk of ectopic pregnancy: a case
      controlled study.
AB  - A case controlled study among 361 women with surgically treated ectopic pregnancy
      and 420 women delivered at term was designed, aiming at characterization of the
      association among previous pelvic operations, selected reproductive factors and
      ectopic pregnancy. All types of previous pelvic operations increase the risk of
      ectopic pregnancy from a 2-fold increase for appendectomy to a 9-fold increase
      for ectopic pregnancy, if maternal age, parity, history of spontaneous and
      induced abortions and history of infertility is controlled. This study suggests
      that a previous pelvic operation may increase the risk of ectopic pregnancy.

PMID- 1356840
TI  - Nonsurgical treatment of ectopic pregnancy.
AB  - Expectant management and medical treatment of ectopic pregnancy either
      systemically or locally are reviewed. Because of the risks of tubal rupture, this
      nonsurgical management should be done with utmost care. To date, surgical removal
      of an ectopic pregnancy remains the method of choice and this can be safely done
      by laparoscopy. Alternate treatments should be carefully evaluated in clinical
      trials.

PMID- 1356841
TI  - Trends in postabortal mortality and morbidity in Ibadan, Nigeria.
AB  - Illegally induced abortion at the University College Hospital, Ibadan increased
      steadily over a 10-year period (1980-1989) despite increasing availability of
      family planning services. Abortion was the commonest cause of death in the
      gynecology service during the period of the study and constituted 36.6% of
      fatalities. The majority of patients (76.2%) did not accept contraceptives.
      Almost one-third of the illegal terminations were performed by physicians.
      Although the percentage of deaths decreased, the contribution of physicians to
      these fatalities increased, and accounted for 6/9 (66.7%) of fatalities in 1989.
      This circumstance probably signifies a defect in physician training and ability
      to perform abortion aftercare. Physicians should be trained in abortion care and
      laws changed in conjunction with greater drive to improve contraceptive
      utilization and reduce the incidence of unsafely induced abortion.

PMID- 1356842
TI  - Mullerian adenosarcoma of the uterus in adolescents.
AB  - A case of uterine Mullerian tumor in an adolescent is described. Surgical and
      clinical management is discussed, based on the experience gained by the analysis
      of cases described in the literature. A review of the different age groups,
      primary sites, surgical management and biological behavior of cases described in
      the literature is tabulated and analysed.

PMID- 1356843
TI  - Elective cesarean hysterectomy for uterine fibroids.

PMID- 1356844
TI  - Rupture of noncommunicating rudimentary uterine horn pregnancy.

PMID- 1356845
TI  - Leiomyoma of the fallopian tube: an unusual cause of abdominal pain.

PMID- 1356846
TI  - Antimicrobial therapy for gynecologic infections. ACOG Technical Bulletin Number
      153--March 1991.
AB  - Therapeutic antimicrobial regimens for pelvic infections must provide coverage
      for aerobic streptococci, common gram-negative enteric bacilli, and anaerobic
      organisms. Careful attention must be given to antibiotic choice as well as the
      dose and duration of therapy. The judicious use of a brief perioperative course
      of antimicrobial prophylaxis is effective in preventing infection following
      certain gynecologic surgical procedures.

PMID- 1356847
TI  - Multifetal pregnancy reduction and selective fetal termination. ACOG committee
      opinion: Committee on Ethics. Number 94--April 1991.

PMID- 1356848
TI  - Reproductive health: a key to a brighter future.

PMID- 1356849
TI  - Pregnancy in hemoglobin sickle cell patients at the University College Hospital,
      Ibadan.
AB  - A retrospective review of pregnancy outcome in hemoglobin (Hbsc) patients managed
      at the University College Hospital, Ibadan over a 5-year period (1984-1988) was
      carried out. The main antenatal complications included anemia (51.2%), bacterial
      infection (22.0%), bone pain crisis (7.3%) and preeclampsia (2.4%). Intrapartum
      complications included anemia (29.2%), bone pain crisis (12.2%) and pseudotoxemia
      (4.9%). The maternal and perinatal mortality rate were 48 and 195 per 1000,
      respectively. The duration of labor and operative delivery rate were not
      different from the general population.

PMID- 1356850
TI  - Fetal binocular distance as a predictor of menstrual age.
AB  - The relation between fetal binocular distance and menstrual age was determined by
      cross-sectional analysis of 555 normal fetuses (14-40 weeks) using real-time
      sonography. Mathematical modelling of the data demonstrated that the binocular
      distance growth curve, similar to the biparietal diameter, is nonlinear.
      Predicted binocular values at various points in gestation were comparable to the
      results of other investigators. Predicted menstrual age in weeks for specific
      binocular distance measurements in millimeters were calculated and are reported
      in tabular form. The variability (+/- 2 SD) associated with predicting menstrual
      age from binocular distance is +/- 14 days between 14 and 27 weeks, but between
      29 and 40 weeks the variability is +/- 24 days. Binocular distance can be used as
      an adjunct in estimating menstrual age and may be useful in the diagnosis of some
      abnormalities, e.g. hypotelorism or hypertelorism.

PMID- 1356852
TI  - Amniotic fluid turbidity: a useful adjunct for assessing fetal pulmonary maturity
      status.
AB  - A rapid, very simple technique for establishing fetal pulmonary maturity status
      is presented. Among 100 receiving amniocenteses, aspiration of turbid amniotic
      fluid that would not permit the reading of newsprint through it was associated
      with a lecithin/sphingomyelin (LS) ratio of greater than or equal to 2.0, or the
      presence of phosphatidyl glycerol (PG) in 97% (specificity 98%, positive
      predictive value 97%). The authors conclude that when turbid fluid is aspirated,
      delay until LS and PG results are known may not be necessary.

PMID- 1356851
TI  - A randomized controlled trial of valethamate bromide in acceleration of labor.
AB  - A randomized controlled study of valethamate bromide administered by
      intramuscular injection in acceleration of labor was done in 60 consecutive
      primigravidae and 60 consecutive multigravidae admitted in labor at 2-4 cm
      cervical dilatation. There was no difference observed in the rate of cervical
      dilatation between those who received valethamate bromide and those who received
      normal saline. However, maternal tachycardia was observed in significantly more
      women primigravida RR 1.97, 95% CI 1.3-3.0; multigravida RR 2.16, 95% CI 1.3-3.6)
      who had received valethamate bromide.

PMID- 1356853
TI  - Protein kinase C inhibits histamine H2 receptor-mediated stimulation of cyclic
      AMP content in the human gastric cancer cell line HGT-1.

PMID- 1356854
TI  - IL-6 and soluble IL-2 receptor in rheumatoid arthritis patients treated with
      second line drugs.

PMID- 1356855
TI  - A retinoid-inducible protein is present in developing cerebellar neurones.

PMID- 1356856
TI  - The relation of the expression and function of the neuronal glycoprotein Thy-1 to
      axonal growth.

PMID- 1356857
TI  - Regulation of brain neurotransmitter release and of adenylate cyclase activity by
      opioid receptors.

PMID- 1356858
TI  - Haem-dependent activation of cytosolic guanylate cyclase by nitric oxide: a
      widespread signal transduction mechanism.

PMID- 1356859
TI  - The midgestational human fetal pancreas contains cells coexpressing islet
      hormones.
AB  - In the fetal development of the mouse pancreas, endocrine cells have been found
      that express more than one hormone simultaneously. Our objective was to evaluate
      the existence of such cells in the human fetal pancreas. We found cells
      coexpressing two of the major pancreatic hormones (insulin, glucagon, and
      somatostatin) in sections of eight midgestational (12-18 weeks) pancreata and in
      0-7% of cells in single-cell suspensions from midgestational pancreata. By
      electron microscopy, using granule morphology and immunoelectron microscopic
      techniques, we could confirm these findings and even detect cells containing
      three hormones. Morphologically different granules contained different
      immunoreactivities, suggesting parallel regulation of hormone production and
      packaging. In six newborn pancreata (born after 22-40 weeks of gestation), we
      could not find any multiple-hormone-containing cells. Subsequently, we evaluated
      whether multiple-hormone-containing cells proliferate by using pancreatic
      fragments and single-cell preparations at the light and electron microscopic
      level (six pancreata). No endocrine hormone-containing cells incorporated
      bromodeoxyuridine during a 1-hr culture period, indicating that these cells have
      lost the ability to proliferate under the conditions chosen. We conclude that, as
      in mice, the human fetal pancreas of 12-18 weeks of gestation contains endocrine
      cells that express multiple hormones simultaneously. These (multiple) hormone
      containing cells do not seem to proliferate under basal conditions.

PMID- 1356860
TI  - Ultrastructural studies of the ontogeny of fetal human and porcine endocrine
      pancreas, with special reference to colocalization of the four major islet
      hormones.
AB  - Most, if not all, endocrine cells seem capable of synthesizing and storing more
      than one hormone. Such cellular colocalization of hormones can be due either to
      the presence of two or more specific granules within the cells or to
      colocalization of the hormones within a single granule. The present study was
      performed to clarify the subcellular localization of insulin, glucagon,
      somatostatin, and pancreatic polypeptide within the endocrine cells of the human
      and porcine pancreas during fetal development, with special reference to possible
      colocalization of the hormones. The tissue specimens were processed for
      ultrastructural cytochemistry using Lowicryl as embedding medium. An immunogold
      labeling technique was used with two parallel, but not interacting, antibody
      chains. Sections from each specimen were double labeled in different combinations
      giving a complete covering of the four major islet hormones. During fetal life
      (50-90 days prenatally in porcine pancreas, 14 weeks gestation in the human
      pancreas) several hormones were demonstrated, not only in the same endocrine
      cells, but also in the same secretory granules (polyhormonal granules). Costorage
      of insulin, glucagon, somatostatin, and pancreatic polypeptide was demonstrated
      in granules in pancreatic endocrine fetal cells. At an early fetal stage, the
      endocrine cells contained either dense, round granules or pale, heteromorphous
      granules. With increasing age and maturation of the endocrine cells, structural
      differentiation of the secretory granules was found to be associated with a
      gradual disappearance of the polyhormonal granules. The first genuine
      monohormonal cell to appear in the porcine fetus was the pancreatic polypeptide
      cell (at 70 days gestation); it was followed by the somatostatin-producing
      endocrine cell. Mature insulin- and glucagon-producing cells were only
      demonstrated after birth. Thus, in the adult pancreatic endocrine cells, each
      specific endocrine cell type produced only one of the four classical hormones.
      The present investigation demonstrated that the endocrine cells of the fetal, but
      not the adult, pancreas are able to synthesize all the major islet hormones, and
      that these peptides are costored in the same granule. The data obtained support
      the concept of a common precursor stem cell for pancreatic hormone-producing
      cells.

PMID- 1356861
TI  - Impact of insulin deficiency on glucose fluxes and muscle glucose metabolism
      during exercise.
AB  - Exercise in the insulin-deficient diabetic state is characterized by a further
      increase in elevated circulating glucose and NEFA levels and by excessive
      counterregulatory hormone levels. The aim of this study was to distinguish the
      direct glucoregulatory effects of insulinopenia during exercise from the indirect
      effects that result from the metabolic and hormonal environment that accompanies
      insulin deficiency. For this purpose, dogs underwent 90 min of treadmill exercise
      during SRIF infusion with (SRIF + INS, n = 8) or without (SRIF - INS, n = 6)
      intraportal insulin replacement. Glucagon was not replaced, thus allowing
      assessment of the direct effect of insulinopenia at the liver independent of the
      potentiation of glucagon action. Glucose was infused to maintain euglycemia.
      Hepatic glucose production (Ra); glucose utilization (Rd); and LGlcU, LGlcE, and
      LGlcO were assessed with tracers ([3H]glucose, [14C]glucose) and arteriovenous
      differences. With exercise, insulin fell from 66 +/- 6 to 42 +/- 6 pM in the SRIF
      + INS group, and was undetectable in the SRIF - INS group. Plasma glucose was
      6.33 +/- 0.38 and 6.26 +/- 0.30 mM at rest in the SRIF + INS and SRIF - INS
      groups, respectively, and was unchanged with exercise. Ra rose from 7.5 +/- 2.3
      to 16.5 +/- 2.2 mumol.kg-1.min-1 and 9.1 +/- 2.0 to 31.4 +/- 3.9 mumol.kg-1.min-1
      with exercise in the SRIF + INS and SRIF - INS groups, whereas Rd rose from 19.5
      +/- 2.0 to 46.8 +/- 3.9 mumol.kg-1.min-1 and 15.1 +/- 1.8 to 29.9 +/- 3.3
      mumol.kg-1.min-1. LGlcU rose from 36 +/- 9 to 112 +/- 25 mumol/min and 15 +/- 4
      to 59 +/- 13 mumol/min and LGlcO rose from 5 +/- 2 to 61 +/- 12 mumol/min and 5
      +/- 3 to 32 +/- 9 mumol/min with exercise in the SRIF+INS and SRIF-INS groups,
      respectively. Arterial levels and limb balances of NEFAs and glycerol were
      similar in the two groups. In summary, during exercise: 1) marked insulinopenia
      attenuates the increases in muscle glucose uptake and oxidation by approximately
      50%, independent of changes in circulating metabolic substrate levels; 2)
      substantial increases in muscle glucose uptake and oxidation are, however, still
      present even in the absence of detectable insulin levels; and 3) insulinopenia
      facilitates the increase in Ra, independent of the potentiation of basal glucagon
      action. In conclusion, marked insulinopenia contributes directly to the
      exacerbation of glucoregulation during exercise in the diabetic state by limiting
      the rises in glucose uptake and metabolism and by enhancing hepatic glucose
      production.

PMID- 1356862
TI  - Does computed tomography have a role in the evaluation of complicated acute
      bacterial meningitis in childhood?
AB  - The authors examined the records of 30 children with bacterial meningitis to
      review the role of computed tomography (CT) of the brain in acute management of
      the disease. CT was normal for 10 patients, six of whom had clinical evidence of
      raised ICP. CT identified an underlying surgical abnormality in two patients with
      progressive focal neurological signs. One patient had unsuspected gross
      hydrocephalus diagnosed by CT, which required neurosurgery. This study shows that
      the management of bacterial meningitis is influenced by CT in only a minority of
      cases; for patients with clinical signs of raised ICP, it was found to be
      insensitive in confirming the clinical diagnosis and establishing an underlying
      cause. However, CT remains valuable in the management of children with
      progressive neurological signs for whom neurosurgical intervention may be
      necessary.

PMID- 1356863
TI  - Duration of acid suppression in H2-antagonist nonresponders.
AB  - We monitored 24-hour gastric acidity in 16 resistant duodenal ulcer patients
      treated with ranitidine 300 mg hora somni (9 cases) and famotidine 40 mg hora
      somni (7 cases) for 3 months. Data obtained in these patients were compared with
      those of a group of unselected duodenal ulcer patients who responded to a 4-week
      course of the same H2-antagonist regimens. In the time window 22.00-07.59 h there
      was a reduced effectiveness of ranitidine in nonresponder patients in terms of
      both mean pH levels (4.8 +/- 0.9 vs. 5.6 +/- 0.7, p < 0.04) and the mean duration
      of the antisecretory effect defined as the time spent in minutes above pH 3.0
      (403 +/- 73 vs. 490 +/- 59, p < 0.02). Also, the action of famotidine was
      diminished in nonresponder patients in the same time interval as regards both pH
      values (4.1 +/- 1.6 vs. 5.7 +/- 0.6, p < 0.03) and the duration in minutes (329
      +/- 163 vs. 473 +/- 45, p < 0.05). The analysis of all individual nonresponder
      patients shows that there was a certain variability in the duration of acid
      suppression: the majority of them had an adequate nocturnal acid inhibition,
      while in some cases of both the ranitidine and the famotidine subgroups, acid
      inhibition lasted only few hours or did not occur at all. At present, it is not
      possible to distinguish with certainty two different subsets of H2-antagonist
      nonresponders because of the small size of the population studied.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1356864
TI  - Somatostatin versus secretin in the treatment of actively bleeding gastric
      erosions.
AB  - In a double-blind, prospective, randomized trial, 63 patients with actively
      bleeding gastric erosions were treated with somatostatin (31 patients) or
      secretin (32 patients). Both drugs were administered by intravenous infusions for
      48 or 72 h. The active bleeding and the effect of the therapy was endoscopically
      established. Somatostatin had a significantly (p < 0.05) better effect on the
      control of bleeding (29 vs. 23 patients), transfusion requirements (5.8 vs. 7.4
      units, p < 0.01) and on the need of surgery (1 vs. 6 patients, p < 0.01). The
      mortality and the rebleeding rate did not differ between the two groups. The
      results show that somatostatin is more effective than secretin in the control of
      active bleeding form gastric erosions.

PMID- 1356866
TI  - Acid-related diseases: improving the treatment options. Symposium proceedings.
      Vienna, November 1991.

PMID- 1356865
TI  - Gastric antisecretory effects of esaprazole in rats.
AB  - The effects of esaprazole on gastric secretion (volume, pepsin and acid output)
      were investigated on animal models, both in vivo and in vitro. In conscious rats
      whose vagal activity was stimulated by pylorus ligation, esaprazole decreased
      volume, acid output and pepsin secretion. In anaesthetized stomach-perfused rats,
      esaprazole inhibited gastric acid secretion evoked by both vagus nerve
      stimulation or bethanechol infusion. By contrast, on isolated guinea-pig gastric
      fundus, esaprazole failed to counteract the acid output stimulated by histamine,
      bethanechol or pentagastrin. In addition to this, phasic contractions evoked by
      acetylcholine on isolated guinea-pig ileum were antagonized by esaprazole only at
      high concentrations. The present results suggest that the inhibitory actions of
      esaprazole on secretory parameters involve the cholinergic parasympathetic
      pathway, probably through both direct and indirect mechanisms.

PMID- 1356867
TI  - The role of acid regulation in the treatment of NSAID-induced mucosal damage.
AB  - Gastric acid probably exacerbates mucosal injury caused by non-steroidal anti
      inflammatory drugs (NSAIDs) in two ways: first, by increasing absorption of
      NSAIDs, which are weak acids and predominantly in their undissociated form at low
      pH--this is probably mainly relevant for salicylates; then, by a 'second wave' of
      injury that leads to deeper erosions, as gastric acid accesses the partially
      denuded mucosa. Regulation of gastric acid secretion by acid-inhibitory drugs has
      been shown to decrease acute NSAID-induced injury to varying extents, depending
      on the drug used and the method of assessing mucosal damage. Healing of chronic
      NSAID-induced ulcers is slow if NSAID therapy is continued, but is facilitated by
      treatment with H2-receptor antagonists or prostaglandins. One study of the acid
      pump inhibitor omeprazole has shown a high rate of healing, even though NSAID
      therapy was continued.

PMID- 1356868
TI  - Medical therapy of patients with reflux oesophagitis poorly responsive to H2
      receptor antagonist therapy.
AB  - There is substantial clinical experience of omeprazole treatment in patients with
      reflux oesophagitis, who have an incomplete or failed response to profound and
      prolonged acid-inhibitory therapy with H2-receptor antagonists. In The
      Netherlands, most patients with reflux oesophagitis poorly responsive to high
      dose H2-receptor antagonists were healed within 3 months of treatment with
      omeprazole, 40 mg once daily. Only a few patients (less than 10%) with
      complicated reflux oesophagitis needed a longer duration of treatment or a higher
      dose of omeprazole to achieve complete endoscopic healing. Follow-up for up to 6
      years has shown that most of these patients could be maintained successfully on
      omeprazole, 20 mg daily. However, about one third of the patients relapsed after
      healing when the maintenance dose was introduced. Evaluation of these patients
      who relapsed has shown that they require a higher level of acid-secretory
      inhibition; a maintenance dose of omeprazole, 40 mg once daily, rehealed the
      oesophagitis within 3 months. Only a few patients had a second relapse, and these
      patients were rehealed by an increase of the omeprazole dose to 60 mg daily.
      Oesophageal pH monitoring in these patients has shown that there is continued
      pathological oesophageal acid exposure, predominantly during the night,
      suggesting that the duration of major action of omeprazole was insufficient for
      production of adequate elevation of intragastric pH during the night. Successful
      control of reflux disease in these patients was achieved by increasing omeprazole
      therapy to a regime and dosage that achieved elevation of intragastric pH above 4
      throughout the 24-hour period.

PMID- 1356869
TI  - Acid suppression in the long-term treatment of peptic stricture and Barrett's
      oesophagus.
AB  - Peptic stricture and Barrett's oesophagus are not only the major, but also the
      most common, complications of gastro-oesophageal reflux disease. The clinical
      problems that these manifestations present are highly significant, and in
      patients with peptic stricture the resultant dysphagia can be a major disability
      that causes nutritional problems. Dilation of a stricture exposes the patient to
      a small, but significant, risk of oesophageal perforation. Barrett's oesophagus
      per se rarely causes morbidity, but carries a significant risk of developing
      oesophageal carcinoma, with its attendant morbidity and mortality. Successful
      anti-reflux surgery for peptic stricture and Barrett's oesophagus effectively
      abolishes pathological oesophageal acid exposure and provides the best indicator
      of the potential benefits that may be obtained from treatment with acid
      inhibitory drugs. The reported experience clearly indicates that successful anti
      reflux surgery results in resolution of peptic stricture following initial
      dilation, concomitant with persistent control of oesophageal acid exposure. In
      patients with Barrett's oesophagus, healing of oesophagitis is well documented
      after successful surgery, but it is unclear whether the Barrett's epithelium
      progresses or regresses significantly in all but a minority of patients. It is
      now established that acid pump inhibition can reduce pathological oesophageal
      acid exposure as effectively as successful anti-reflux surgery. In a minority of
      patients, however, omeprazole, 40 or 60 mg daily, divided into two doses, is
      necessary to achieve this effect. This is particularly true for patients with the
      more severe forms of disease, in whom peptic stricture and Barrett's oesophagus
      are most prevalent. Results indicate that peptic stricture can resolve during
      effective gastric acid inhibition with omeprazole, and results from controlled
      trials on the management of these patients with omeprazole are awaited.
      Similarly, there are reports of regression of Barrett's oesophagus during
      omeprazole therapy, but the completeness and predictability of any such effect
      have not yet been adequately evaluated. There is sufficient experience from long
      term omeprazole treatment of gastro-oesophageal reflux disease to indicate that
      maintenance of a satisfactory response of peptic stricture or Barrett's
      oesophagus depends upon continued effective gastric acid inhibition.

PMID- 1356870
TI  - [Cryptosporidiosis].

PMID- 1356871
TI  - Preferential location of somatostatin receptors in germinal centers of human gut
      lymphoid tissue.
AB  - Somatostatin receptors were evaluated in four human gut-associated lymphoid
      tissues (palatine tonsils, ileal Peyer patches, vermiform appendix, and colonic
      solitary lymphatic follicles) using receptor autoradiography on tissue sections
      incubated with 125I[Tyr3]octreotide. All four tissues were somatostatin-receptor
      positive; the receptors were preferentially located in the germinal centers, with
      the luminal part of the center more strongly labeled than the basal part. The
      corona of the follicles and the primary follicles without germinal centers did
      not display somatostatin receptors. The receptors were of high affinity (Kd = 1.3
      +/- 0.6 nmol/L) and specific for somatostatin. Displacement by nanomolar
      concentrations of somatostatin 14, somatostatin 28, and octreotide was observed,
      as was guanosine triphosphate dependency. The gastrointestinal mucosa and the
      plexus submucosus and myentericus also contained somatostatin receptors. These
      data strongly suggest that the germinal centers of the gut-associated lymphoid
      tissue are a site of action of somatostatin. It possibly mediates
      antiproliferative effects and inhibits immunoglobulin synthesis in the activated
      lymphoid cells. The human gut represents a multifaceted target for somatostatin
      action, in which at least three different tissues (mucosa, nerve plexus, and
      lymphoid tissue) are involved.

PMID- 1356872
TI  - Intestinal fat does not inhibit gastric function through a hormonal somatostatin
      mechanism in dogs.
AB  - In awake dogs with chronic gastric, duodenal, and jejunal fistulas, F(ab)1
      fragments of somatostatin monoclonal antibody (mAb S607) were administered
      intravenously (IV) to test the hypothesis that intraintestinal lipid inhibits
      peptone-stimulated gastric acid secretion and emptying by a hormonal somatostatin
      mechanism. Plasma somatostatin was increased significantly by duodenal and
      jejunal perfusion with 20% lipid. Somatostatin administered IV caused dose
      dependent inhibition of meal-stimulated gastric acid secretion and gastric
      emptying similar to that seen after intestinal perfusion with lipid.
      Administration of mAb S607 F(ab)1 fragments significantly reversed somatostatin
      (400 pmol.kg-1.h-1, IV)-induced inhibition of peptone-stimulated acid output and
      gastric emptying. Acid output inhibited by intraduodenal lipid was reversed
      partially after F(ab)1 administration, but the inhibitory effect of intrajejunal
      lipid was not altered. Inhibition of acid secretion by IV somatostatin and by
      intraintestinal fat was not caused by a decrease in circulating gastrin
      concentrations. Gastric emptying delayed by intraintestinal lipid was unaffected
      by antibody administration. Somatostatin does not appear to be a major hormonal
      mediator of intestinal fat-induced inhibition of gastric acid secretion or
      delayed gastric emptying in dogs.

PMID- 1356873
TI  - Effect of chymotrypsin on rat blood pressure.
AB  - 1. Chymotrypsin (Cht) administration (14 mg/kg, i.v.) to rats always caused
      hypertension; hypotension preceded this effect in 64% of the observations (n =
      11). 2. A 68% reduction of circulating kininogen but not of angiotensinogen was
      observed after Cht administration. 3. Cht effects were not affected by captopril,
      [Sar1-Leu8]-angiotensin II and alpha-adrenoceptor antagonists. In 70% of the
      observations (n = 10) hypotension was abolished by a mixture of histamine H1- and
      H2-antagonists. Therefore histamine release may explain hypotension. 4. Cht
      released in vitro from rat plasma, a substance producing hypertension in the rat
      and contraction of the guinea-pig ileum. Both effects were antagonized by [Sar1
      Leu8]-angiotensin II. 5. In spite of this angiotensin release in vitro, the
      hypertensive component of the in vivo response to Cht seems to be due to some
      other substance.

PMID- 1356874
TI  - Opposite influences of dopaminergic receptor subtypes on penile erection.
AB  - 1. Mixed D-1/D-2 dopamine agonist apomorphine induced a penile erection (PE) in
      rats in a biphasic manner. 2. The response was decreased with increasing doses of
      the drug. 3. The maximum effect was obtained by 0.1 mg/kg of apomorphine. 4. In
      animals pretreated with D-1 antagonist SCH 23390, high doses of apomorphine
      showed higher PE response, while D-2 antagonist sulpiride pretreatment decreased
      the response of the low doses of the drug. 5. The inhibitory effect of sulpiride
      was dose-dependent. 6. The D-2 agonists bromocriptine or quinpirole induced a
      dose-dependent PE. 7. The effects of both drugs were decreased by sulpiride or
      SKF 38393 pretreatment. 8. Cholinergic drugs physostigmine and neostigmine did
      not induce PE, but antimuscarinic agent atropine decreased the effects of
      apomorphine, bromocriptine or quinpirole. 9. It is concluded that D-2 dopamine
      receptor stimulation may induce PE, while D-1 activation elicit an opposite
      effect. 10. However, cholinergic stimulation is not able to induce PE,
      cholinergic inhibition may decrease the PE induced by dopaminergic agents.

PMID- 1356875
TI  - Mechanism of ebrotidine protection against gastric mucosal injury induced by
      ethanol.
AB  - 1. The gastroprotective properties of a new H2-receptor antagonist, ebrotidine,
      against ethanol-induced mucosal injury was investigated. 2. Groups of rats, with
      and without indomethacin pretreatment, received intragastrically either a dose of
      ebrotidine or vehicle only, followed by ethanol given at various intervals up to
      4 hr. The gastric mucosa, 30 min after the ethanol challenge, was then subjected
      to macroscopic and histologic examination, and physicochemical measurements. 3.
      Ebrotidine at doses of 50 mg and higher per kg body wt effectively prevented the
      alcohol-induced mucosal injury, even in the presence of indomethacin. The
      protective effect was demonstrable already at 30 min, reached maximum at 1 hr,
      and persisted up to 3 hr. 4. Physicochemical analyses established that ebrotidine
      elicited 30% increase in mucus gel dimension, caused 19-20% increase in
      glycolipids and phospholipids, and evoked 21% increase in sulfomucin and 18% in
      sialomucins. As a consequence, the mucus gel viscosity increased by 1.4-fold, H+
      retardation capacity by 16%, and hydrophobicity by 65%. 5. The results
      demonstrate that ebrotidine is a unique H2-antagonist endowed with a remarkable
      mucosal strengthening capability.

PMID- 1356876
TI  - Biphasic effect of tetraethylammonium on canine purkinje fibre action potential
      configuration.
AB  - 1. Using conventional microelectrode techniques a biphasic effect of
      tetraethylammonium (5 mmol/l) on the configuration of action potentials recorded
      from isolated canine Purkinje fibres: action potentials were first shortened
      (early effect) and then lengthened (late effect) by tetraethylammonium. 2. The
      early effect of tetraethylammonium also included lengthening of phase 1 duration
      and elevation of the plateau amplitude. These early effects reached steady-state
      within the first 3 min of superfusion and were readily reversed within 3 min of
      initiating washout of the drug. 3. The late effect (gradual lengthening of
      repolarisation during phase 3) failed to reach steady-state within the initial 60
      min of superfusion and was not reversible. 4. The early effects of
      tetraethylammonium were more marked at slow driving rates and were not affected
      by blockade of alpha- and beta-adrenoceptors using 1 mumol/l phentolamine and 1
      mumol/l propranolol. 5. The early effects of tetraethylammonium were mimicked by
      4-aminopyridine (0.5 mmol/l), and in the presence of 4-aminopyridine
      tetraethylammonium failed to induce further changes in action potential
      morphology. 6. The early effects of tetraethylammonium may be due to inhibition
      of the transient outward current. 7. The rapid onset and reversibility of these
      early effects suggest that tetraethylammonium may act from outside the cell
      membrane.

PMID- 1356877
TI  - Analgesic effect of benzodiazepines and flumazenil.
AB  - 1. In the present work the analgesic effect of benzodiazepines (BZD) and
      flumazenil (FLU) using the writhing test in mice was studied. 2.
      Intracerebroventricular administration of BZD exhibited a dose-dependent
      antinociceptive effect when compared to control value. 3. Intracerebroventricular
      administration of FLU induced a dose-dependent antinociceptive action that was
      not antagonized by naloxone (NX). 4. BZD administered as subcutaneous pellets
      produced an antinociceptive action in the writhing test, when compared to control
      mice, only at relative high doses and was partially antagonized by naloxone. 5.
      These findings could be explained assuming that NX and/or FLU have partial
      agonist properties in a common receptor which mediates the antinociceptive
      action. 6. The antinociceptive action of BZD could be related to an increased
      release of adenosine, which by itself has analgesic effects.

PMID- 1356878
TI  - Modulation of noradrenergic transmission in the rat isolated portal vein: role of
      prejunctional alpha 2-adrenoceptors and beta-adrenoceptors.
AB  - 1. The effect of several adrenoceptor agonists and antagonists on the spontaneous
      and stimulus-evoked release of [3H]noradrenaline was studied in rat isolated
      portal vein. 2. Yohimbine (10(-6)M) increased the stimulus-evoked
      [3H]noradrenaline efflux. Adrenaline alone (3 x 10(-6)M) was without effect,
      while it increased the resting efflux when added together with yohimbine. 3.
      Propranolol alone was without effect on the release of [3H]noradrenaline. When
      added (2 x 10(-6)M) at the same time as yohimbine, it reduced the stimulation
      induced 3H efflux. When added before adrenaline and yohimbine, propranolol (10(
      5)M) reduced both spontaneous and stimulus-evoked release of [3H]noradrenaline.
      4. The effect of several beta-blocking drugs was measured on the enhancing effect
      of yohimbine on the stimulation-evoked 3H efflux. The beta 1-adrenoceptor
      blocking drugs: atenolol (5 x 10(-6) and 10(-5) M), metoprolol (5 x 10(-6) and
      10(-5) M), like the more selective bisoprolol (2 x 10(-6) and 4 x 10(-6) M)
      inhibited yohimbine activity. Likewise, propranolol (2 x 10(-6) and 5 x 10(-6)M)
      and the beta 2-adrenoceptor blocker ICI 118551 exhibited an antagonistic effect.
      5. These results indicate the possibility for noradrenaline to activate
      presynaptic beta-adrenoceptors in rat portal vein. They show an interaction
      between the presynpatic alpha 2- and beta-adrenoceptor mediated systems in the
      release of noradrenaline. They suggest the presence and the activity of
      facilitatory beta 1-adrenoceptors.

PMID- 1356879
TI  - The occurrence and in vitro effects of molecules potentially active in the
      control of growth in the marine mussel Mytilus edulis L.
AB  - A molecular with a molecular weight, estimated by gel filtration, of
      approximately 22 kDa and immunoreactive to anti-human hypophysial growth hormone
      (hGH) has been identified by radioimmunoassay in the digestive gland and
      hemolymph of the mussel Mytilus edulis L. The dilution curve of this molecule was
      parallel to that of hGH, suggesting that the antigenic site of the Mytilus
      molecule is similar to that of hGH. Immunoreactive fractions resulting from gel
      filtration failed to stimulate protein synthesis in dispersed mantle-edge cells
      in vitro. No hGH-immunoreactive material was detected in the cerebral ganglia. It
      is thus clear that a small protein-synthesis-stimulating factor (PSSF),
      identified in the cerebral ganglia and hemolymph by its action in vitro on
      dispersed mantle-edge cells, is not analogous to the Mytilus hGH-immunoreactive
      molecule. Likewise, a somatostatin-immunoreactive molecule present in the
      hemolymph of Mytilus did not coelute with PSSF. Evidence is presented that PSSF
      is a hydrophilic peptide that stimulates DNA, RNA, and protein synthesis and that
      is not tissue specific. These characteristics suggest that PSSF is a growth
      hormone.

PMID- 1356880
TI  - Neurohormonal control of growth and carbohydrate metabolism by the light green
      cells in Lymnaea stagnalis.
AB  - The neuroendocrine light green cells (LGCs), 4 clusters of together approximately
      150 giant neurons in the cerebral ganglia of the freshwater gastropod, Lymnaea
      stagnalis, have been suggested to be involved in the control of growth. The
      present study examines in greater detail this role and possible actions on energy
      metabolism. Growth indices (total body and organ wet and dry weights, as well as
      protein and DNA contents of the organs) and metabolic indices (tissue lipid,
      polysaccharide and glucose levels) were compared in LGC extirpated/reimplanted
      with control groups. LGC extirpation in rapidly growing juvenile snails
      immediately arrested growth, which was restored by reimplantation of cerebral
      ganglia with LGCs but not by cerebral ganglia without LGCs, indicating their
      neuroendocrine control of growth. The LGCs stimulate a pattern of organ growth,
      which is in proportion to the growth of the whole body except for the shell,
      which shows a disproportionally faster growth due to calcium deposition over the
      whole surface. The data on protein and DNA in the organs strongly suggest that
      the LGCs induce growth by stimulating cell multiplication. The LGCs maintain low
      tissue glycogen reserves and hemolymph concentrations of both glycogen and
      glucose. The secretions of these cells stimulate the uptake of glucose by the
      growing tissues with no apparent effects on lipid metabolism.

PMID- 1356881
TI  - An immunocytochemical study of the endocrine pancreas in three genera of
      lacertids.
AB  - The comparative morphology of the endocrine pancreas was studied in 11 species of
      lacertids. Four major cell types were identified immunocytochemically in the
      endocrine pancreas: glucagon-immunoreactive A-cells, insulin-immunoreactive B
      cells, somatostatin-(SRIF)-immunoreactive D-cells, and pancreatic polypeptide(PP)
      immunoreactive F-cells. Different distributions of the four cell types were seen
      in the endocrine tissue within the exocrine parenchyma. F-cells were rare or
      absent in the splenic lobe and abundant in the duodenal lobe, in which they were
      usually widespread in the exocrine parenchyma and rarer in the islets. The other
      three cell types were always present in the islets. The central core consisted of
      B- and A-cells, with B-cells predominating. The peripheral mantle was formed by A
      cells and less abundant D-cells. Rare D-cells were also found in the central
      core. D- and F-cells showed projections often closely associated with
      capillaries. The observed arrangements in islets and isolated cells may represent
      an endocrine network that, in addition to systemic actions, may regulate exocrine
      function in a paracrine fashion.

PMID- 1356882
TI  - Dietary intake and gene variation influence the response of plasma lipids to
      dietary intervention.
AB  - We have examined whether variation at the apolipoprotein (apo) B, apo E, apo AII,
      and apo AI-CIII-AIV genes affected the relationship between dietary intake and
      serum lipid traits in individuals who had participated in dietary intervention
      from a basal high fat diet to a low fat diet followed by a return to their
      natural diet, the switchback. On both the basal and switchback diets where the
      variance of dietary intake was great, there was a significant correlation between
      P/S ratio and serum total, low-density lipoprotein (LDL) cholesterol, and apo AI
      levels. In addition dietary cholesterol (dchol) levels correlated significantly
      with serum apo AI levels on the basal diet. Comparing the difference between
      basal and intervention (delta 1) and between switchback and intervention diets
      (delta 2), changes in dchol and P/S ratio correlated significantly with changes
      in serum total, high-density lipoprotein (HDL) and LDL cholesterol, and apo B
      levels. There was a significant correlation between monounsaturated fatty acid
      (MUFA) and apo AI levels during both changes. Furthermore we have examined
      whether the relationship between variables was homogeneous among genotypes of
      candidate gene polymorphisms. A heterogeneous effect (P less than 0.01) was seen
      among genotypes of the PvuII-AIV restriction fragment length polymorphism (RFLP)
      on the correlation of serum LDL cholesterol levels and dietary MUFA during both
      dietary changes (delta 1 and delta 2). A heterogeneous effect among genotypes of
      the apo B XbaI RFLP on the correlation between dchol versus total and LDL
      cholesterol during the change delta 1, but not delta 2, was observed. Thus our
      results show that both dietary components and genetic variation affect the
      response of serum lipid, lipoprotein, and apolipoprotein levels to dietary
      change.

PMID- 1356883
TI  - Sexual development genes of Neurospora crassa.
AB  - The filamentous fungus Neurospora crassa undergoes a complex program of sexual
      development to form a fruiting body composed of several kinds of specialized
      tissue. Subtractive hybridization was used to isolate genes that are expressed
      preferentially during this sexual phase. Many such sexual development (sdv) genes
      were identified in a cosmid library of Neurospora genomic DNA. Fourteen of the
      sdv genes were subcloned, and their expression in mutant strains and under
      crossing and vegetative growth conditions was examined. All of the regulated
      transcripts were less abundant (and in many cases not detectable) in strains
      grown under vegetative (high nitrogen) conditions, suggesting that nitrogen
      starvation is required for their synthesis. The expression of most of the sdv
      genes also required a functional A mating type product, even under crossing
      growth conditions, suggesting that this product functions as a master control in
      sexual development. To determine if the products of the sdv genes play essential
      roles in the sexual cycle, a reverse-genetic approach (based on RIP (repeat
      induced point mutation)-mediated gene disruptions) was used to create mutations
      in the genes. A mutant strain (asd-1) with a recessive crossing defect
      (apparently caused by the RIP process) was isolated; in this strain, early
      development is normal and may asci are formed, but ascospores are never
      delineated. A second recessive mutant strain (asd-2) was apparently created by
      ectopic integration of the transforming DNA into a gene required for the sexual
      process; in this strain the sexual process was blocked at an early stage, and the
      ascogeneous tissue underwent little development.

PMID- 1356884
TI  - Heteroplasmy of short tandem repeats in mitochondrial DNA of Atlantic cod, Gadus
      morhua.
AB  - The mitochondrial DNA of the Atlantic cod (Gadus morhua) contains a tandem array
      of 40-bp repeats in the D-loop region of the molecule. Variation among molecules
      in the copy number of these repeats results in mtDNA length variation and
      heteroplasmy (the presence of more than one form of mtDNA in an individual). In a
      sample of fish collected from different localities around Iceland and off
      George's Bank, each individual was heteroplasmic for two or more mtDNAs ranging
      in repeat copy number from two (common) to six (rare). An earlier report on mtDNA
      heteroplasmy in sturgeon (Acipenser transmontanus) presented a competitive
      displacement model for length mutations in mtDNAs containing tandem arrays and
      the cod data deviate from this model. Depending on the nature of putative
      secondary structures and the location of D-loop strand termination, additional
      mechanisms of length mutation may be needed to explain the range of mtDNA length
      variants maintained in these populations. The balance between genetic drift and
      mutation in maintaining this length polymorphism is estimated through a
      hierarchical analysis of diversity of mtDNA length variation in the Iceland
      samples. Eighty percent of the diversity lies within individuals, 8% among
      individuals and 12% among localities. An estimate of theta = 2N(eo) mu greater
      than 1 indicates that this system is characterized by a high mutation rate and is
      governed primarily by deterministic dynamics. The sequences of repeat arrays from
      fish collected in Norway, Iceland and George's Bank show no nucleotide variation
      suggesting that there is very little substructuring to the North Atlantic cod
      population.

PMID- 1356885
TI  - The Rhizobium leguminosarum biovar phaseoli glnT gene, encoding glutamine
      synthetase III.
AB  - Plasmid pGE203 contains the Rhizobium leguminosarum biovar phaseoli glnT locus.
      Glutamine synthetase III (GSIII) was purified from a glutamine auxotrophic strain
      of Klebsiella pneumoniae carrying this plasmid. Sequencing of a 2.4-kb fragment
      containing the glnT locus reveals an open reading frame of 435 amino acids (aa),
      whose first eight aa are identical to those determined from pure GSIII by direct
      aa sequencing, thus confirming that glnT indeed codes for GSIII activity. The
      comparison of the GSIII aa sequence with the reported sequence of GSs from other
      organisms shows a significant degree of homology. Since the three-dimensional
      structure of GS from Salmonella typhimurium is known, a three-dimensional model
      of GSIII was built by homology.

PMID- 1356886
TI  - Sequences of the genes encoding the minor tip components of Pap-3 pili of
      Escherichia coli.
AB  - We report the sequence of the papE, papF and papG genes from the O75:K5
      uropathogenic P pili variant, Pap-3. Comparison of the deduced amino acid
      sequences with those of other P pili variants reveals regions of complete
      homology, as well as regions of variation. Analysis of the variations in the
      hydrophilic domains of these proteins will help elucidate the residues which
      determine binding specificity.

PMID- 1356887
TI  - Three year follow up of patients with gastrooesophageal reflux disease.
AB  - Data on the natural course of gastrooesophageal reflux disease are sparse. One
      hundred and sixty six patients with typical reflux symptoms (heartburn and/or
      acid regurgitation) and pathologic pH monitoring (reflux time > 8.2% upright
      and/or > 3.0% supine) were studied. The patients were followed up by
      questionnaire and interview for a mean of 41 (seven to 86) months after diagnosis
      of reflux disease. Ten patients had died of diseases not reflux related. In 117
      (75%) of the remaining 156 patients data on the course of gastrooesophageal
      reflux disease could be obtained. In 12 patients anti reflux surgery had been
      performed. Forty one (39%) of the remaining 105 patients have stopped taking
      medical therapy, in 13 of these patients symptoms had completely disappeared.
      Sixty four patients continued on medication (40 on demand, 24 regularly). When
      asked how their symptoms would be if they completely stopped medication, 71
      patients considered their symptoms to be equal or worse and 21 patients to be
      improved as compared with the initial investigation. Patients with persisting
      symptoms at follow up had significantly more supine reflux (p < 0.05) at the
      initial pH monitoring as compared with patients with improved symptoms. The
      presence and grade of oesophageal erosions at initial endoscopy, duration of
      symptoms, age, sex, and smoking habits had no influence on the course of
      gastrooesophageal reflux disease. In conclusion, reflux symptoms disappear only
      in a minority of patients with proven gastrooesophageal reflux disease. More than
      half of all patients continue medication, either on demand or regularly. Severe
      supine reflux is an unfavourable prognostic factor.

PMID- 1356888
TI  - Intestinal hypersecretion of the refed starved rat: a model for alimentary
      diarrhoea.
AB  - Fluid transport was gravimetrically measured in vivo in the duodenum, jejunum,
      and ileum of anaesthetised fed, 72 hour starved and 72 hour starved rats refed
      for up to five days after starvation. Basal unstimulated fluid transport was
      monitored by instilling 0.9% NaCl into the lumen and measuring the gain or loss
      in weight of the closed intestinal loop. Fluid was absorbed in all the areas of
      the intestine in the fed rats. Increasing basal fluid absorption was observed in
      the duodenum over the three days of starvation but in the jejunum there was no
      significant change. In the ileum, the pattern was very different, on day 1 the
      fluid was absorbed but on days 2 and 3 there was an increasing secretion of
      fluid. Refeeding the rats with their normal diet restored the basal absorption of
      fluid in the duodenum within 24 hours, had no effect in the jejunum but in the
      case of the ileum the hypersecretion of fluid observed in the day 3 starved rat
      was maintained on day 1 of refeeding, increased further on day 2, decreased on
      day 3 but returned to absorption on day 4. The normal absorption was restored to
      the ileum on day 5 of refeeding. Fluid secretion was induced in all the rat
      groups by bethanechol (ip 60 micrograms/kg bw) a stable cholinergic agonist, PGE2
      (ip 10 micrograms/kg (bw) and E coli STa (luminally instilled, 500 ng/ml) a
      secretory enterotoxin. All the secretagogues gave enhanced secretion compared
      with the fed by day 2 of starvation which increased considerably on day 3.
      Refeeding returned their secretion back to the fed level in the duodenum within
      24 hours, in the jejunum within 48 hours but in the ileum their induced secretion
      on day 2 of refeeding was greater than that of the day 2 of refeeding was greater
      than that of day 3 starved and took until day 4 to return to the fed levels for
      behanechol and PGE2 and until day 5 for E. coli STa. This behaviour of rat small
      intestine showing even greater hypersecretion in the refed state than the starved
      mimics the human condition of alimentary induced diarrhoea where incautious
      feeding of starved humans induces severe, often lethal diarrhoea. The refed
      starved rat appears to be a possible model for this condition.

PMID- 1356889
TI  - [Beginning which week of pregnancy is therapy with betamimetics useful? Beta
      receptor density in the course of pregnancy?].

PMID- 1356890
TI  - Proliferative activity of human uterine leiomyoma cells as measured by automatic
      image analysis.
AB  - Proliferative activity of uterine leiomyomas from premenopausal (n = 44) and
      postmenopausal (n = 12) women was investigated by automatic image analysis on
      frozen tissue sections using immunohistochemistry with anti-proliferating cell
      nuclear antigen antibody. The quantitative proliferation index (QPI) in
      premenopausal leiomyoma cells was significantly (p < 0.025) higher than that in
      leiomyomas in postmenopausal women. Leiomyomas proliferated most actively during
      the secretory phase. After the climacterium, leiomyomas showed no proliferative
      activity in the absence of hormone supply, while combined substitution with
      estrogen and progestagen considerably increased QPI.

PMID- 1356891
TI  - Molecular pathology of inherited erythrocyte membrane disorders: hereditary
      spherocytosis and elliptocytosis.
AB  - Hereditary spherocytosis and elliptocytosis are common genetic defects of the red
      blood cell membrane skeleton. In recent years rapid advances have been made in
      the knowledge of the protein structure and assembly of the cytoskeleton. Thanks
      to the wide use of protein analysis methods several alterations have been
      discovered in functionally important domains of the different cytoskeletal
      proteins in these diseases. The cloning of cDNA for the majority of the
      cytoskeletal proteins allows us to begin elucidating some of these defects at the
      DNA level. This paper will review the effects of recent advances upon:
      cytoskeleton structure and assembly; molecular pathology of spherocytosis,
      elliptocytosis and pyropoikilocytosis.

PMID- 1356893
TI  - Therapy of acute leukemia: highlights of the Fifth International Symposium on
      Therapy of Acute Leukemia, held in Roma on 1-6 November, 1991.

PMID- 1356892
TI  - A case of Langerhans histiocytosis with HIV-like immunodeficiency.
AB  - A case of histiocytosis X (Langerhans type) associated with bullous pulmonary
      emphysema and acquired immune deficiency, regarding CD4 positive cells, is
      described. Previous history was remarkable for skin lesions which first appeared
      in 1981 and progressively worsened, diabetes insipidus diagnosed in 1986, and
      bullous pulmonary emphysema detected in 1988. Biopsy results of skin lesions were
      consistent with histiocytosis X. Thyroid gland involvement was found by means of
      cytological examination. The search for HIV infection (also performed by means of
      immunoblotting and PCR) was negative. To our knowledge the immunodeficiency
      detected in histiocytosis X affects the T suppressor lymphocyte subset, so we
      thought this peculiar case was worth describing.

PMID- 1356895
TI  - [Neurotransmission and nitric oxide (NO)].
AB  - The history of how we reached the goal of determining the mechanism of
      vasodilatation caused by non-adrenergic, non-cholinergic nerve stimulation in
      cerebral arteries was traced. We concluded from this project that electrical and
      chemical (by nicotine) stimulations evoke an increased influx of Ca2+ into nerve
      terminals and activate nitric oxide (NO) synthase, resulting in the synthesis and
      release of NO that stimulates the guanylate cyclase in smooth muscle, thereby
      causing the accumulation of cyclic GMP and eliciting muscle relaxation. Reviewed
      also are the neurally-induced inhibitory responses of extracranial arteries,
      intestines, etc. with respect to NO.

PMID- 1356894
TI  - Selection of a new multidrug resistant cell line from Friend leukemia cells by
      short and cyclic exposures to high concentrations of daunorubicin.
AB  - BACKGROUND: Resistance of tumor cells to cytotoxic agents can be due to the
      overexpression of the mdr 1 gene, which encodes a plasma membrane protein (P
      glycoprotein). To understand the molecular basis of multidrug resistance, several
      laboratories have isolated cell lines resistant to doxorubicin, actinomycin D,
      vinca alkaloids and related agents. Many months or years of culture with
      gradually increasing concentrations of cytotoxic agents are necessary to obtain a
      resistant cell line. METHODS: We selected a new multidrug resistant cell line
      (MELC-DRTL) by 24-hour cycles of exposure to relatively high concentrations of
      daunorubicin from sensitive Friend Leukemia cells. After each cycle, the residual
      live cells were expanded up to the density of 1 x 10(6) cells/ml. RESULTS: The
      assay conducted with MoAb C-219 showed a high expression on the membrane surface
      of P-glycoprotein in the MELC-DRTL line, but the fact that it was impossible to
      obtain a complete reversal of the resistance, even when using high concentrations
      of verapamil, suggests the presence of other mechanisms unrelated to the presence
      of P-glycoprotein. CONCLUSIONS: The kind of cellular resistance induction used in
      this experiment enabled us to obtain an MDR cell line in three months of culture.

PMID- 1356896
TI  - [The role of beta-adrenoceptor subtypes in cardiac contractility].
AB  - Since the existence of beta 3-adrenoceptors in various organs has been
      established, it is necessary to re-evaluate the subtypes of beta-adrenoceptors in
      cardiac muscle. We have demonstrated the possible existence of three subtypes of
      beta-adrenoceptors: beta 2-adrenoceptors, high-affinity beta 1-adrenoceptors (the
      so-called beta 1-adrenoceptors) and the low-affinity beta 1-adrenoceptors (akin
      to beta 3-adrenoceptors) in canine cardiac muscle, which are coupled with
      increases in myocardial cyclic AMP content and positive inotropic effects. Cyclic
      AMP generated by the activation of the high-affinity beta 1-adrenoceptors seems
      to be coupled with the positive inotropic effect much more effectively than via
      beta 2- or low-affinity beta 1-adrenoceptors. Stimulation of beta 2-adrenoceptors
      or the low affinity beta 1-adrenoceptor is causally related to the development of
      tolerance and to the adverse effects of nonselective beta-full agonists. It is
      conceivable that with denopamine, unlike with isoproterenol, tolerance can hardly
      develop, and there are no adverse effects resulting from its partial agonistic
      property and its selectivity for the high-affinity beta 1-adrenoceptors. The
      selective stimulation of the high-affinity beta 1-adrenoceptors would be
      beneficial for the management of mild congestive heart failure. In contrast,
      stimulation of the low-affinity beta 1-adrenoceptors by endogenous catecholamines
      or nonselective beta-agonists will contribute to deteriorating hemodynamic,
      symptomatic and prognostic consequences in patients with congestive heart
      failure.

PMID- 1356897
TI  - [Effects of FRG-8813, a new type histamine H2-receptor antagonist, on various
      experimental gastric and duodenal lesions in rats].
AB  - We examined the anti-ulcer effects of FRG-8813, a new type histamine H2-receptor
      antagonist, on various experimental gastric and duodenal lesions in rats. FRG
      8813, administered orally, inhibited the formation of lesions dose-dependently in
      experimental models with the exception of the Shay ulcer model. The anti-ulcer
      potency of FRG-8813 was 4 approximately 10 times greater than that of cimetidine
      when the ED50 values of both compounds were compared. Famotidine and cimetidine
      inhibited lesion formation at higher doses than the anti-secretory doses. The
      anti-ulcer action of FRG-8813, however, appeared at even lower doses than those
      of anti-secretory action. These results suggest that FRG-8813 is able to prevent
      lesion formation with anti-secretory action plus other mechanisms unlike typical
      histamine H2-receptor antagonists.

PMID- 1356898
TI  - [Effects of FRG-8813, a new-type histamine H2-receptor antagonist, on the healing
      of gastric and duodenal ulcer in rats and spontaneously ulcerative mice].
AB  - We examined the anti-ulcer effects of FRG-8813, a new-type histamine H2-receptor
      antagonist, in chronic ulcer models of rats and mice (W/WV). FRG-8813, given
      orally twice a day for 7 days, accelerated the healing of gastric or duodenal
      ulcer induced by acetic acid injection or application at the non-antisecretory
      doses (0.3 approximately 3 mg/kg). Administration of FRG-8813 to rats with ulcers
      increased the amounts of mucus in the gastric mucosa. These actions of FRG-8813
      were more potent than those of famotidine or cimetidine. In W/WV mice, several
      ulcers spontaneously developed on gastric mucosa during the 8 weeks after the
      birth. The ulcers were aggravated by several unknown factors after the ulcer
      generation in W/WV mice. The aggravation of ulcers was inhibited by the 4-week
      administration of FRG-8813 with diet at the dose of 1 or 10 mg/kg/day, but was
      not inhibited by cimetidine at the dose of 100 mg/kg/day. From these results, we
      suggest that FRG-8813 is able to accelerate the healing of ulcers by
      antisecretory plus increasing actions on the integrity of the gastric mucosal
      defense mechanisms; therefore FRG-8813 is expected to be a useful drug for the
      treatment of gastric or duodenal ulcers in humans.

PMID- 1356899
TI  - [Effects of beta blockers on lipoprotein metabolism].
AB  - PROBLEM: With respect to prevention of its most common complication--mortality
      from coronary heart disease--treatment of hypertension had disappointed. It is
      possible that this is due to negative effects of antihypertensives on lipid
      metabolism. MAJOR TOPICS: The effects of beta blockers on lipid metabolism can be
      differentiated principally, in accordance with the classification of beta
      blockers into those with and those without intrinsic sympathomimetic activity
      (ISA), as also selectivity and non-selectivity. Thus, non-selective beta blockers
      with no ISA usually lead to an increase in triglycerides of 25% to 30%, and a
      decrease in HDL cholesterol of about 15%. On average, beta-1 selective blockers
      result in a smaller increase in triglycerides. Beta blockers with ISA, in
      contrast, are largely neutral vis-a-vis lipid metabolism. In the individual case,
      in particular in the presence of hyperlipoproteinemia, the effects cannot be
      reliably predicted. CONCLUSIONS: Lipoprotein concentrations should be monitored
      during treatment with beta blockers. If necessary, a change in the agent employed
      is recommended. In the case of prevention of a second myocardial infarction, for
      which various studies have unequivocally shown a reduction in mortality
      associated with treatment with beta blockers with no ISA, these side effects
      will, however, be accepted--with the exception of extreme changes--for a limited
      period of time.

PMID- 1356900
TI  - New mechanisms of hormone secretion: MDR-like gene products as extrusion pumps
      for hormones?
AB  - P-glycoprotein, the product of the multidrug resistance (MDR1) gene, is an ATP
      driven transmembrane pump that increases the resistance of cells by actively
      exporting toxic chemicals. In addition to transporting anticancer drugs, P
      glycoprotein has been reported to extrude a variety of lipophilic drugs, such as
      calcium channel blockers, phenothiazines, cyclosporines etc. Interestingly,
      recent experiments suggest that steroid hormones may be physiologic substrates
      for P-glycoprotein. In addition, there exists a family of transporter genes with
      high structural homology to P-glycoprotein, the so-called ABC (ATP-binding
      casette) family. Although the physiological ligands for most of these
      transporters are unknown, there is increasing evidence that peptides may be
      transported by some of these proteins. Thus, the a-factor, a farnesylated
      pheromone with 13 amino acids, is exported from yeast cells by the product of the
      STE6 gene, a transporter protein with high homology to P-glycoprotein. Recently,
      we have cloned a novel member of the ABC-transporter gene family from
      neuroblastoma x glioma hybrid (NG-108-15) cells. This putative transporter gene
      ("NG-TRA") is expressed in the adrenal gland, kidney and in the brain. High
      amounts of NG-TRA mRNA are found in a variety of human brain tumors. Whether NG
      TRA and/or other MDR-related transporters are involved in the transport of
      steroids, peptide hormones or growth factors remains to be established. If so,
      the cellular export of hormones by active pumps may represent a new mechanism of
      hormone secretion.

PMID- 1356901
TI  - Molecular analysis of the androgen receptor gene in 52 patients with complete or
      partial androgen insensitivity syndrome: a collaborative study.
AB  - In patients with androgen insensitivity syndrome (AIS), RFLP study of the
      androgen receptor gene made it possible to analyze whether deletions or mutations
      could be responsible for abnormalities in androgen responsiveness. We studied
      RFLPs of DNA from 25 46,XY patients with partial AIS (PAIS), defined as a
      concentration of androgen receptor in genital-skin fibroblasts less than 340
      fmol/mg DNA, and DNA from 27 46,XY patients with complete AIS (CAIS) with no
      detectable androgen receptor site. DNA samples were digested with BamHI, EcoRI,
      HindIII and TaqI restriction enzymes and hybridized with three cDNA probes
      covering the three domains of the androgen receptor. When we had the maternal and
      an unaffected brother's DNA, we analyzed the two androgen receptor gene
      polymorphisms described, the HindIII and the exon 1 CAG repeat polymorphisms, in
      order to distinguish the two maternal X chromosomes, and to detect carriers of
      AIS. We did not find any large deletion among the 52 patients. We observed a
      heterozygous mother in 3 of 14 families studied with the HindIII polymorphism,
      and in 12 of 25 families using the exon 1 CAG repeat polymorphism. This study
      suggests that in AIS, abnormalities in androgen receptor response could be
      related to point mutations or microdeletions rather than to gross structural
      alterations of the androgen receptor gene. Furthermore, unless the point mutation
      has been described, exon 1 and HindIII polymorphism studies would enable the
      identification of carriers in 50% of families, and the prenatal diagnosis of AIS.

PMID- 1356902
TI  - Serum thyrotropin response to combined arginine and thyrotropin-releasing hormone
      administration provides evidence for an altered somatostatinergic tone in
      acromegaly.
AB  - The aim of this study was to evaluate plasma thyrotropin (TSH), prolactin (PRL)
      and growth hormone (GH) responses to the TSH-releasing hormone (TRH) test and to
      a combined arginine-TRH test (ATT-TRH) in 10 normal subjects and in 15
      acromegalic patients. In controls, TSH responsiveness to TRH was enhanced by ATT
      (p less than 0.001). When considering the 15 acromegalic patients as a whole, no
      significant difference in TSH responses was detected during the two tests.
      However, patients without suppression of plasma GH levels after oral glucose load
      showed an increased TSH responsiveness to the ATT-TRH test if compared to TRH
      alone (p less than 0.025), while patients with partial suppression of plasma GH
      levels after glucose ingestion showed a decreased TSH responsiveness to ATT-TRH
      (p less than 0.05). No difference was recorded in PRL and GH responses, evaluated
      as area under the curve, during TRH or ATT-TRH tests in controls and in
      acromegalics. In conclusion, (1) normal subjects have an enhanced TSH response to
      the ATT-TRH test and (2) acromegalic patients without suppression of GH levels
      after oral glucose load show a TSH responsiveness to the ATT-TRH test similar to
      that of controls, while acromegalics with partial GH suppression after oral
      glucose load have a decreased TSH responsiveness to the ATT-TRH test. These data
      suggest that acromegaly is a heterogeneous disease as far as the
      somatostatinergic tone is concerned.

PMID- 1356903
TI  - Monitoring of neurotransmitter amino acids by means of an indwelling cisterna
      magna catheter: a comparison of two rodent models of fulminant liver failure.
AB  - Alterations of brain and cerebrospinal fluid amino acids have consistently been
      described in human and experimental fulminant liver failure. To evaluate the
      significance of such changes in the pathogenesis of hepatic encephalopathy in
      fulminant liver failure, brain and cerebrospinal fluid amino acids (glutamate,
      aspartate, GABA, glycine, taurine) were measured at various stages during the
      development of neurological dysfunction in rats after hepatic devascularization
      or thioacetamide treatment to induce acute liver failure. To facilitate
      repetitive removal of cerebrospinal fluid, a technique employing long-term
      implantation of cisterna magna catheters in conscious, freely moving rats was
      developed. Brain but not cerebrospinal fluid concentrations of the excitatory
      amino acids glutamate and aspartate were reduced in both animal models of
      fulminant liver failure in parallel with deterioration of neurological status.
      Brain and cerebrospinal fluid GABA levels were not significantly altered.
      Cerebrospinal fluid glycine levels were increased two to three times in parallel
      with increasing brain glycine content in the devascularized rat but were
      unchanged in thioacetamide-induced liver failure, suggesting distinct
      pathophysiological mechanisms in these two experimental situations. On the other
      hand, onset of coma in both animal models of fulminant liver failure was
      accompanied by significantly increased cerebrospinal fluid taurine levels. We
      suggest that such changes result from taurine release from astrocytes in brain
      into the extracellular fluid; this is consistent with taurine's role in the
      regulation of intracellular osmolarity in brain. Sequential measurements of amino
      acids in the cerebrospinal fluid of small rodents with indwelling cisterna magna
      catheters adds a useful new approach for exploring the neurobiology of hepatic
      encephalopathy in fulminant liver failure.

PMID- 1356904
TI  - Expression of leukocyte adhesion molecules (ICAM-1/LFA-1) related to clinical
      behaviour in B cell lymphomas.
AB  - We investigated the expression of adhesion molecules of lymphocyte function
      associated antigen-1 alpha (LFA-1 alpha) and its ligand intercellular adhesion
      molecule-1 (ICAM-1) on 74 well-characterized B cell lymphomas. The LFA-1 was
      expressed on B cell lymphomas (21/74; 28 per cent), but to a lesser degree than
      ICAM-1 which was highly expressed (48/74 cases; 64 per cent). From the results of
      bone marrow examination of 39 cases with B cell lymphomas, 13 of 16 cases with a
      lack of ICAM-1 molecule showed a higher incidence of marrow involvement, but nine
      of 23 cases with the expression of ICAM-1 molecule showed a lower incidence.
      These findings suggest that the lack of expression of the ICAM-1 molecule by B
      cell lymphomas correlates with bone marrow involvement by lymphoma cells (p <
      0.05). Expression of the LFA-1 molecule appears not to correlate with marrow
      involvement (p < 0.05).

PMID- 1356905
TI  - Expression of p170 protein in multiple myeloma: a clinical study.
AB  - The expression of the p170 multidrug resistance protein by bone marrow plasma
      cells (BMPC) was assessed at clinical presentation in 53 patients with multiple
      myeloma (MM) using the C219 monoclonal antibody. Twenty-two of the 53 (41 per
      cent) patients had variable aliquots (1-60 per cent, median = 6 per cent) of
      p170+ BMPC by immunocytochemistry. Five of 10 patients studied using bivariate
      flow cytometry had both diploid and hyperdiploid (DNA index ranged from 1.2 to
      1.5) BMPC with hyperdiploid clones having significantly greater p170 expression
      than diploid ones. Of the 37 patients evaluated for a response, 20 (54 per cent)
      had responded to induction chemotherapy. The presence of p170+ BMPC was a
      negative indicator for achieving response. The response rate was 75 per cent for
      p170- and 25 per cent for p170+ cases (p < 0.01), with no difference on the basis
      of treatment schedule (melphalan and prednisone, 24 patients; peptichemio,
      vincristine and prednisone, 13 patients). No difference in response and survival
      duration was found between p170+ and p170- patients. In six of nine patients
      studied both at diagnosis and following induction chemotherapy the p170+ BMPC%
      increased irrespective of the type of treatment or outcome.

PMID- 1356907
TI  - Immunohistochemical comparison of chromogranins A and B and secretogranin II with
      calcitonin and calcitonin gene-related peptide expression in normal, hyperplastic
      and neoplastic C-cells of the human thyroid.
AB  - Normal and hyperplastic thyroid C-cells and 14 cases of medullary thyroid
      carcinoma were investigated immunohistochemically with antibodies against
      chromogranins A and B, secretogranin II, calcitonin and calcitonin gene-related
      peptide (CGRP). Normal and hyperplastic C-cells showed strong calcitonin and
      chromogranin A immunoreactivity whereas CGRP, chromogranin B and secretogranin II
      expression was less intense. Strong calcitonin and chromogranin A
      immunoreactivity was also found in the majority of tumour cells in medullary
      thyroid carcinoma. The CGRP, chromogranin B and secretogranin II staining
      observed was present in variable patterns. In some cases CGRP, chromogranin B and
      secretogranin II could only be demonstrated in isolated tumour cells with
      elongated processes suggestive of neuronal differentiation of these cells. The
      biological function(s) of the chromogranins/secretogranins remain(s) still
      unclear. There is evidence that these proteins are pro-peptides which give rise
      to functionally active compounds. Studies on normal C-cells and medullary thyroid
      carcinoma may elucidate the role of chromogranins/secretogranins in endocrine and
      neuronal cells.

PMID- 1356906
TI  - Immunochemical investigation of insulinomas for islet amyloid polypeptide and
      insulin: evidence for differential synthesis and storage.
AB  - An affinity purified antibody to fragment 14-29 of islet amyloid polypeptide
      (IAPP) has been prepared. This antibody, which does not cross-react with the
      related molecule calcitonin gene-related peptide, was used to investigate
      immunochemically the presence of IAPP in normal and neoplastic human pancreatic
      endocrine tissue. The pattern of IAPP staining in normal pancreas mirrors that of
      insulin, although slight differences were observed. In neoplastic tissue, IAPP
      was found in 16 out of 19 tumours that were positive for insulin, and was absent
      from one tumour negative for insulin. In some cases there were differences in the
      staining patterns of IAPP and insulin. These results suggest that the synthesis
      and secretion of IAPP and insulin are not inter-dependent and support the concept
      that IAPP has a discrete biological function. Islet amyloid polypeptide was found
      in six out of six insulinoma amyloid deposits, suggesting that the peptide is an
      invariable component of these deposits. Over-expression of IAPP, with aberrant
      processing and/or secretion, may be the causative factor for amyloid deposition
      in insulinomas and in the islets of type 2 (non-insulin dependent) diabetic
      patients. Investigation of patients with insulinomas and of insulin cells in
      culture and tissue sections may help to clarify the biological function of IAPP.

PMID- 1356908
TI  - A practitioner's guide to use of psychotropic medication in liquid form.

PMID- 1356909
TI  - Detection of c-erbB-2 activation in paraffin-embedded tissue by
      immunohistochemistry.
AB  - Commercially available monoclonal antibodies were tested for their ability to
      detect increased levels of c-erbB-2 protein in formalin-fixed, paraffin-embedded
      breast carcinomas. Of five antibodies studied, four (TAB-250, CB11, 3B5, and
      N3/D10) showed strong cytoplasmic membrane reactivity in 23% (11 of 47) of
      routinely processed tumors, although interpretation of the immunoreactivity with
      3B5 and N3/D10 occasionally was difficult due to cytoplasmic granular staining.
      Since the c-erbB-2 oncogene is activated by DNA amplification and overexpression
      of mRNA and protein, the same tumors were analyzed for c-erbB-2 activation by
      other techniques. c-erbB-2 activation in these 11 tumors was confirmed by
      immunohistochemistry of frozen tissue (nine of nine tumors), in situ
      hybridization (nine of 11 tumors), and Southern blot analysis (five of eight
      tumors). In some of these tumors the failure to demonstrate c-erbB-2 DNA
      amplification may be due to the small percentage of malignant cells. One
      additional tumor showed probable c-erbB-2 protein overproduction based on strong
      immunoreactivity with two antibodies (TAB-250 and CB11), although no definite
      activation could be demonstrated by additional techniques. Three other tumors
      (6%) showed equivocal c-erbB-2 protein overproduction based on weak
      immunoreactivity only with TAB-250, although unequivocal activation could not be
      demonstrated by additional techniques. The 32 carcinomas (68%) that showed no
      significant immunoreactivity with any antibodies in routinely processed tissue
      also showed no detectable c-erbB-2 activation by additional techniques. We
      conclude that TAB-250 and CB11 are reliable antibodies for detecting c-erbB-2
      protein overproduction in routinely processed tissue. TAB-250 also weakly stains
      a few tumors showing no definite c-erbB-2 activation by other techniques. Two
      additional antibodies (3B5 and N3/D10) detect c-erbB-2 protein overproduction in
      paraffin-embedded tissue, but are more difficult to interpret. A fifth antibody,
      TA-1, is an excellent reagent for use on frozen tissue, but prolonged formalin
      fixation may impair recognition of its antigenic epitope.

PMID- 1356910
TI  - Elevated CD4 antigen expression among activated T cells in lymph nodes draining
      mammary regions chronically exposed to Staphylococcus aureus antigen.
AB  - We examined the cell cycle distribution and subset marker characteristics of
      mucosal-associated supramammary lymph node (MALN) T cell subpopulations at sites
      proximal and distal to the mammary region of animals repeatedly injected with
      Staphylococcus aureus antigen. Multiparameter flow cytometric analysis of
      draining MALNs showed that CD4+ T cells expressed significantly greater amounts
      of CD4 surface antigen than corresponding cell populations in non-draining MALNs.
      In contrast, the intensity of CD8 surface antigen expression among draining MALN
      CD8+ cells remained unchanged. Draining and non-draining MALNs contained nearly
      equal proportions of large CD4+ T cell subpopulations (CD4/CD8 ratio) with the
      former having greater cell numbers undergoing active DNA synthesis (S + G2M
      phase) in vivo. Similarly, draining MALNs had greater cell numbers of small CD4+
      lymphocytes in the S + G2M phase, although with lower CD4/CD8 ratios of
      corresponding cell populations in non-draining MALNs. This study demonstrates
      that prolonged exposure with Staph aureus antigen enhances the cell number and
      expression of CD4 surface antigen among T lymphocyte subpopulations actively
      synthesizing DNA in draining MALNs. The role of the CD4 antigen in inflammatory
      responses at sites proximal (draining) and distal (non draining) to chronic
      infection within the mammary/mucosal immune network is discussed.

PMID- 1356911
TI  - Various membrane proteins of Francisella tularensis induce interferon-gamma
      production in both CD4+ and CD8+ T cells of primed humans.
AB  - Tularaemia is an intracellular infection, which is controlled by the host as a
      result of an immunospecific T-cell response. A crucial product of the responding
      T cells is interferon-gamma (IFN-gamma), which acts by enhancing the microbicidal
      activity of macrophages. T cells of tularaemia-vaccinated individuals respond in
      vitro to a multitude of protein antigens of the vaccine strain Francisella
      tularensis LVS. In the present study, the responses to four of these antigens
      were shown to be confined mostly to the CD45RO+ memory T-cell subset. To
      characterize further the phenotype of the responding cells, purified CD4+ and
      CD8+ T cells were stimulated with the antigens. CD4+ T cells, but not CD8+ T
      cells, proliferated and produced IFN-gamma. However, when CD8+ T cells were
      isolated from bulk cultures of lymphocytes, which had been stimulated with
      antigen for 3 days, they responded to an extent similar to that of CD4+ T cells.
      Purified CD8+ T cells also responded when they were supplemented with interleukin
      2 (IL-2). There was a direct quantitative correlation between the proliferative
      response of CD4+ and CD8+ T cells and their production of IFN-gamma. IL-2 was
      produced in the cultures, the amounts being higher in the cultures of CD4+ than
      in those of CD8+ cells. IL-4 was not detected in the culture medium of any of the
      T-cell subsets. Seventeen human alpha beta + CD4+ CD8- CD3+ T-cell clones,
      specific to antigens of F. tularensis, were raised. When proliferating, these
      clones did invariably produce IL-2 and IFN-gamma but no IL-4. In conclusion, both
      CD4+ and CD8+ T cells of tularaemia-vaccinated individuals respond with
      proliferation to various protein antigens of F. tularensis, and the proliferative
      response is strictly associated with IFN-gamma production. The CD8+ T-cell
      response seems to depend on cytokines supplied by proliferating CD4+ T cells.

PMID- 1356912
TI  - A T-cell response to the anti-arthritic drug penicillamine in the mouse:
      requirements for generation of the drug-derived antigen.
AB  - Mice primed with the anit-arthritic drug D-penicillamine (DP) developed DP
      specific T cells in the draining lymph nodes (DLN) which responded to drug
      haptenated stimulator cells, but not to untreated control cells nor to free drug,
      in in vitro proliferation assays. The responder cells were CD4+ and the response
      was major histocompatibility complex (MHC) class II restricted. The conditions
      required to generate efficient stimulator cells for in vitro proliferation assays
      were investigated. Drug-haptenated syngeneic spleen cells, but not thymocytes,
      were able to stimulate T cells from DP-sensitized mice. However, prolonged
      incubations of spleen cells with DP were required to generate the drug-derived T
      cell antigen. Further experiments revealed that the generation of a DP-derived
      antigenic determinant for T cells did not require intracellular processing, as
      stimulator cells pretreated with fixative or lysosomotropic agents before drug
      haptenation were as effective as untreated DP-haptenated cells in stimulating the
      responder cells to proliferative in vitro. These findings show that the protein
      reactive drug DP can generate a cellular antigen that is capable of stimulating a
      T-cell response. Furthermore, the generation of this antigen appears to bypass
      conventional antigen processing, suggesting perhaps a direct chemical
      modification of cell surface molecules that are involved in immune recognition.
      This process may underlie adverse reactions to DP that are believed to be
      mediated by the cellular immune system.

PMID- 1356913
TI  - Lymphokine secretion and proliferation of intraepithelial lymphocytes from murine
      small intestine.
AB  - Compared to other peripheral lymphocytes, intestinal intraepithelial lymphocytes
      (IEL) have previously been shown to have low proliferative capabilities. However,
      there are two main populations of IEL in the small intestine of mice. First,
      there is the thymus-dependent CD3+,Thy-1+ population, most of which expresses the
      alpha beta T-cell receptor (TcR), and second there is the thymus-independent
      CD3+,Thy-1- population, most of which expresses the gamma delta TcR. In this
      study Thy-1-enriched and Thy-1-depleted lymphocytes from murine intestinal
      epithelium were studied separately for their ability to proliferate and secrete
      lymphokines in vitro after mitogenic stimulation, after stimulation via the TcR
      CD3 complex and after stimulation with the superantigen Staphylococcus aureus B
      (SEB). Here we show that Thy-1-enriched IEL are not an immunocompromised
      population of cells but are functionally competent T cells that are capable of
      proliferation and lymphokine secretion after stimulation with concanavalin A (Con
      A), phorbol myristate acetate (PMA) and anti-CD3 monoclonal antibody (mAb).
      Furthermore, Thy-1-enriched IEL proliferate and secrete lymphokines after
      'superantigenic' stimulation with SEB. In contrast, the majority of Thy-1
      depleted IEL do not proliferate, and secrete only minimal levels of lymphokine to
      any of the stimuli tested in this study.

PMID- 1356914
TI  - A clonal analysis of lung T cells derived by bronchoalveolar lavage of healthy
      individuals.
AB  - The characteristics of the T-cell population in the healthy human lung have been
      investigated by analysing the properties of T-cell clones derived from
      bronchoalveolar lavage (BAL) samples and comparing them with T cells cloned from
      the blood of the same individuals. The proportions of CD4+ and CD8+ T cells in
      the starting populations from BAL and blood were similar although only 14% of BAL
      T cells were CD45RA+ compared to 70% of blood T cells. The precursor frequency of
      T-cell clones derived from BAL was less than from blood. The cytokine profiles
      [after phytohaemagglutinin (PHA) stimulation] of the clones derived from both
      sources were markedly different and these differences lay in the CD4+ population.
      BAL-derived CD4+ clones produced interferon-gamma (IFN-gamma) more frequently
      than did those from blood while blood-derived clones were more likely to produce
      interleukin-2 (IL-2) than those from BAL. IL-4 was produced by the majority of
      BAL- or blood-derived clones (93% and 88% respectively) either along with IFN
      gamma (BAL) or IL-2 (blood). The cytokine profiles of BAL-derived T-cell clones
      are consistent with those derived from lung interstitium and suggest that the BAL
      T-cell populations reflect those in the lung wall. Whether the unique properties
      of lung T cells are acquired after leaving the blood or whether there is
      selective entry of T-cell subpopulations into the lung remains to be determined.

PMID- 1356915
TI  - In vivo inhibition by a monoclonal antibody to CD4+ T cells of humoral and
      cellular immunity in sheep.
AB  - The ability of intravenously injected anti-CD4 and anti-CD8 monoclonal antibody
      (mAb) to deplete specific lymphocyte subsets in vivo and their effects on
      antibody responses to ovalbumin (OVA) and Brucella abortus, and skin reactivity
      to T-cell mitogens was examined in merino lambs. Repeated administration of anti
      CD4 or anti-CD8 mAb caused a specific and sustained depletion of target cells
      from peripheral blood. Anti-CD4 mAb significantly inhibited the in vivo antibody
      response to OVA but had no effect on the antibody response to LPS of B. abortus.
      In contrast, antibody responses to both OVA and B. abortus lipopolysaccharides
      (LPS) remained unaffected in lambs depleted of their CD8+ T lymphocytes. These
      results confirm the T-cell dependence and independence of antibody responses to
      OVA and LPS, respectively. Skin reactions elicited by intradermal injections of
      phytohaemagglutinin (PHA) and concanavalin A (Con A) were also significantly
      suppressed in lambs depleted of their CD4+ T cells, but treatment with anti-CD8
      mAb had no effect on skin responsiveness. Together, these results suggest that
      mAb can be extremely effective at selectively depleting lymphocyte subsets in
      vivo and can be used for studying various aspects of immunoregulation and
      immunity in sheep.

PMID- 1356916
TI  - CD26 induces T-cell proliferation by tyrosine protein phosphorylation.
AB  - CD26 antigen distribution among lymphoid cells and its participation in the
      process of lymphocyte activation and proliferation has been widely documented.
      However, the molecular and biochemical mechanisms coupled to the CD26 molecule
      are not yet known. With different monoclonal antibodies (mAb) we have detected
      that approximately 56% of CD4+ and 35% of CD8+ cells from peripheral blood
      lymphocytes express CD26 and the expression of this antigen is required for
      antigen- but not for mitogen-induced proliferation unless exogenous interleukin-2
      (IL-2) is added to the culture. The stimulation of nylon wool-separated T cells
      and T-cell clones by the anti-CD26 mAb, 134-2C2, induced tyrosine phosphorylation
      on a subset of proteins of 50,000, 46,000, 26,000, 24,000 and 21,000 MW. This
      pattern of phosphorylation was not affected by the presence of 12-myristate 13
      acetate (PMA), although this cofactor is required for CD26-mediated IL-2 mRNA
      expression and T-cell proliferation. When a specific tyrosine kinase inhibitor,
      Tyrphostin, was used in CD4+ cells cultures stimulated with 134-2C2 and PMA, the
      proliferation and the expression of IL-2 mRNA were inhibited. Thus, protein
      tyrosine phosphorylation seems to play a major role in CD26-mediated T-cell
      proliferation.

PMID- 1356917
TI  - Rapid cytokine up-regulation of integrins, complement receptor 1 and HLA-DR on
      monocytes but not on lymphocytes.
AB  - Short-term (3 hr) incubation of whole blood with human recombinant cytokines
      induced rapid changes in the expression of monocyte but not of lymphocyte surface
      molecules. The percentage of monocytes bearing CD11b molecules was enhanced by
      tumour necrosis factor-beta (TNF-beta), whilst that of CD11c was increased by
      both TNF-alpha and TNF-beta. The mean fluorescence intensity (MFI) of monocyte
      CD11a was enhanced by interleukin-2 (IL-2), TNF-alpha and TNF-beta, and that of
      CD11b, CD11c and CD18 was increased by IL-2, IL-4, TNF-alpha and TNF-beta. The
      proportion of monocytes expressing HLA-DR antigens was not modified by the
      cytokines investigated, but its MFI was increased by IL-2, IL-4, TNF-alpha and
      TNF-beta. In contrast, the percentage of monocytes bearing complement receptor 1
      (CD35) was enhanced by IL-2, TNF-alpha and TNF-beta but the MFI of this molecule
      was not modified by these cytokines. The highest up-regulation of CD18, HLA-DR
      and CD35 was observed with 100 U/ml of either IL-2, IL-4, TNF-alpha or TNF-beta.
      Decreasing the concentration of all four cytokines from 100 to 10 and 1 U/ml
      diminished the levels of expression of all molecules, with the exception of CD35,
      which reached its maximum upon incubation with 1 U/ml of TNF-alpha. IL-1 beta, IL
      6 or interferon-gamma (IFN-gamma) did not modify the expression of any of the
      above monocyte surface determinants. Moreover, none of the lymphocyte surface
      molecules investigated was modified by 3-hr incubation of blood with cytokines.
      The demonstration that cytokines selectively and rapidly up-regulate integrins,
      complement receptor 1 and HLA-DR molecules, on monocytes but not on lymphocytes,
      suggests that similar mechanisms of mononuclear cell activation by cytokines may
      control the development and duration of the inflammatory process.

PMID- 1356918
TI  - Functional characterization of protective CD4+ T-cell clones reactive to the
      murine malaria parasite Plasmodium chabaudi.
AB  - Protective immunity to asexual malaria parasites appears to be mediated
      predominantly by the CD4+ subset of T lymphocytes. To examine the role of this T
      cell population in the immune response to the murine malaria parasite Plasmodium
      chabaudi, CD4+ clones derived from infected mice were raised and propagated in
      vitro. Analysis of the reactivity of clones responsive to parasite antigen
      demonstrated that the CD4+ cell response is heterogeneous and is consistent with
      the idea of two functionally distinct CD4+ subsets. Those populations derived
      early during primary infection secreted interleukin-2 (IL-2) and interferon-gamma
      (IFN-gamma) upon antigenic stimulation in vitro, i.e. they had a cytokine
      repertoire typical of the delayed-type inflammatory T-helper 1 (Th1) CD4+ subset.
      In contrast, cells taken after clearance of a secondary infection produced IL-4
      and acted as effective helper cells for anti-malarial antibody (Ab) synthesis in
      vitro, and thereby had the characteristics of Th2 cells. The appearance in vivo
      of Th1 and then Th2 clones specific for P. chabaudi-parasitized erythrocytes
      (pRBC) supports the proposal from limiting culture analyses that for this malaria
      parasite resolution of primary parasitaemia is predominantly through the action
      of cytokines rather than Ab, and that final clearance requires helper cells and
      specific immunoglobulin.

PMID- 1356920
TI  - Larvivorous potential of some indigenous fishes of Sherthallai region with
      special reference to their efficacy in control of mansonioides.
AB  - Larvivorous potential of some indigenous fishes collected from natural habitats
      of Sherthallai region in Kerala state, India, was studied under laboratory as
      well as controlled field conditions. Ophiocephalus striatus was observed to
      consume significantly higher number of mansonioides larvae (354/g body wt/day),
      followed by Macropodus cupanus (231/g body wt/day). The proportion of adult
      vector mosquito emergence was significantly (P less than 0.05) lower in cages
      with fish species studied, as compared to that of control group of cages without
      fishes. Natural food preference of the selected fish species was also studied
      indirectly through gut content analysis.

PMID- 1356919
TI  - Effects of PMA, cytokines and dexamethasone on the expression of cell surface Fc
      receptors and mRNA in U937 cells.
AB  - Fc receptors (FcR) are of importance in immune and inflammatory reactions. FcR
      expression as mRNA and surface protein was therefore examined in the
      myelomonocytic cell line, U937, after stimulation with phorbol ester (PMA), in
      the presence of seven different cytokines (interferon-gamma [IFN gamma], IFN
      alpha, granulocyte-macrophage colony-stimulating factor [GM-CSF], tumour necrosis
      factor-alpha [TNF alpha], TNF beta, interleukin-beta [IL-1 beta], IL-2) or
      dexamethasone. HLA class I and CD11b expression were also examined. Cell surface
      expression of FcRI and II was measured by flow cytometry using monoclonal
      antibodies, and the mRNA of FcRII was measured with cDNA or oligonucleotide
      probes. The major findings were: PMA increased cell surface FcRI, FcRII and
      CD11b, but decreased HLA; PMA caused a fivefold increase in all three FcRII RNA
      transcripts (2.5, 1.5 and 0.9 kb) in Northern analysis; IFN gamma, IFN alpha and
      GM-CSF increased the expression of FcRI and II, and there was no effect with IL-1
      beta, IL-2, TNF alpha or TNF beta (only GM-CSF increased the expression of
      CD11b); all cytokines further increased FcRI and FcRII expression in the presence
      of PMA; HLA expression was also increased in the presence of PMA, IFN alpha and
      IFN gamma; dexamethasone reduced the levels of FcRI and II in cells stimulated
      with PMA with or without cytokines. Thus stimulatory agents and cytokines can
      alter the expression of surface Fc gamma R and mRNA encoding FcRI or II,
      providing potential control mechanisms for the modulation of these receptors in
      inflammatory responses.

PMID- 1356921
TI  - Role of hypothalamic-renal noradrenergic systems in hypotensive action of
      potassium.
AB  - To clarify the role of the renal and hypothalamic noradrenergic systems in the
      antihypertensive actions of dietary potassium supplementation in salt-loaded
      spontaneously hypertensive rats (SHR), we measured systolic blood pressure and
      norepinephrine turnover, which was determined from the rate of decline of tissue
      norepinephrine concentration after the administration of alpha-methyl-p-tyrosine,
      in 5-week-old SHR or age-matched Wistar-Kyoto (WKY) rats eating normal-NaCl
      (0.66%) or high-NaCl (8%) diet with supplementation of 8% KCl. In WKY rats,
      neither high-sodium nor high-potassium diets had an effect on blood pressure with
      no change in renal or hypothalamic norepinephrine turnover. In SHR, however, salt
      loading accelerated the development of hypertension. Potassium supplementation
      did not affect blood pressure in normal-sodium SHR but attenuated the rise in
      blood pressure with salt loads. Correspondingly, renal norepinephrine turnover in
      SHR was increased compared with that of WKY rats, and salt loading further
      potentiated the increased turnover in the kidney; however, no changes in
      hypothalamic turnover occurred. Potassium supplementation attenuated the rise in
      blood pressure with salt loads and the increased renal turnover. Stimulation of
      sympathetic discharge by cold exposure after the administration of alpha-methyl-p
      tyrosine produced marked depletion of norepinephrine in most tissues. The loss of
      norepinephrine was significantly greater in both kidney and hypothalamus of salt
      loaded SHR than in those of normal-sodium SHR, but potassium could normalize
      this. Thus, potassium not only diminished the increased renal norepinephrine
      turnover in the kidney under normal conditions but also attenuated the augmented
      renal and hypothalamic norepinephrine turnover by cold stress in salt-loaded
      SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356922
TI  - Effects of alcohol and caloric restrictions on blood pressure and serum lipids in
      overweight men.
AB  - We have examined the independent and combined effects on blood pressure and blood
      lipids of alcohol restriction and weight loss in overweight male drinkers with a
      view to assessing overall effects on cardiovascular risk of two widely promoted
      nonpharmacological approaches for hypertension. Eighty-six men with a mean age of
      44.3 years, a mean regular alcohol intake of 440 ml/wk (five or six standard
      drinks per day), a mean blood pressure of 137.4 mm Hg systolic and 84.8 mm Hg
      diastolic, and a mean body mass of 92.5 kg entered a controlled two-way factorial
      study. The subjects were randomly assigned to four groups for an 18-week
      intervention in which members of two groups drank only low-alcohol beer, thereby
      reducing their alcohol intake by 374 ml/wk, while those of the other two groups
      continued their normal alcohol intake. Within the low and normal alcohol intake
      groups subjects either continued their usual diet or reduced their caloric intake
      by 4,200-6,300 kJ/day (1,000-1,500 kcal/day) (with protein, fat, and carbohydrate
      provided as 15%, 30%, and 55% of total calories, respectively). Calorie reduction
      and alcohol restriction caused weight losses of 7.5 (p less than 0.001) and 2.1
      (p less than 0.01) kg, respectively. Calorie reduction and alcohol restriction
      were associated with decreases in systolic blood pressure of 5.4 (p less than
      0.001) and 4.8 (p less than 0.01) mm Hg, respectively, and in diastolic blood
      pressure of 4.2 (p less than 0.001) and 3.3 (p less than 0.01) mm Hg,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356923
TI  - Realizing the potential of practice pattern profiling.
AB  - In January 1992, the Physician Payment Review Commission held a conference to
      learn about the appropriateness of present uses of profiling of practice
      patterns, and to identify what will be required to realize the full potential of
      this technique in the future. The conference addressed the data needs of
      profiling, the development of valid and relevant profiles, the impact of profiles
      on medical practice, and controversies surrounding public access to profiling
      information and the uses to which profiling has been put. This paper, based in
      part on that conference, reviews the basic concepts that underlie profiling and
      describes the roles that profiling can play in quality improvement, assessment of
      provider performance, and utilization review. It uses case studies to illustrate
      the types of problems that have arisen in actual usage and discusses what will be
      required to resolve them. The final section describes the roles that profiling
      can play in achieving the goals of health care reform, and concludes with what is
      needed in data and infrastructure development to improve the quality and
      usefulness of profiling.

PMID- 1356924
TI  - Administrative costs in the U.S. health care system: the problem or the solution?
AB  - The estimates of potential savings as a result of reductions in administrative
      costs have generated considerable controversy. In response to this debate, the
      Robert Wood Johnson Foundation sponsored an invitational workshop for
      policymakers, health services researchers, and key stakeholders in the health
      care system. The workshop, conducted by the Alpha Center in February this year,
      provided a framework for identifying, measuring, and weighing the value of
      administrative costs and served as a vehicle for discussion of these issues. This
      article summarizes the presentations, the issues raised, and questions for
      further research. Overall, the papers and presentations emphasized that while the
      focus of attention has been on the controversy over whether particular aggregate
      estimates of administrative costs and potential savings are correct, the
      fundamental underlying issue is how the health care system might best be managed.

PMID- 1356925
TI  - Forecasts of the costs of medical care for persons with HIV: 1992-1995.
AB  - This study concludes that the cumulative (national) cost of treating all persons
      with the human immunodeficiency virus (HIV) rose considerably over the past year
      and will continue to rise over the next several years. It is forecast that the
      cumulative cost of treating all persons with HIV will increase 48% from 1992 to
      1995 (from $10.3 billion to $15.2 billion). It is estimated that the average
      yearly cost of treating a person with AIDS is $38,300 and of treating an infected
      person without AIDS is $10,000. The lifetime cost of treating a PWA is calculated
      to be $102,000. This is the first study to use, along with other data, data from
      the AIDS Cost and Service Utilization Survey to estimate the cost of treating
      persons with the HIV. The study also projects the number of AIDS cases to be
      66,300 in 1992, 76,200 in 1993, 86,800 in 1994, and 97,800 in 1995.

PMID- 1356926
TI  - Molecular analysis of the Haemophilus ducreyi groE heat shock operon.
AB  - Chancroid is a sexually transmitted genital ulcer disease caused by Haemophilus
      ducreyi. Previously, we developed diagnostic DNA probes for H. ducreyi (L. M.
      Parsons, M. Shayegani, A. L. Waring, and L. H. Bopp, J. Clin. Microbiol. 27:1441
      1445, 1989). In the present study, DNA sequencing of one of the diagnostic probes
      revealed two adjacent open reading frames (ORFs). These H. ducreyi ORFs and the
      encoded proteins show significant homology with the groE genes and GroES and
      GroEL heat shock proteins from several bacterial pathogens and with conserved
      eukaryotic 60-kDa heat shock proteins. The first H. ducreyi ORF (groES) is
      preceded by sequences similar to those of the Escherichia coli consensus heat
      shock promoters and is 288 nucleotides long and is capable of encoding a protein
      of 10.3 kDa. The second ORF (groEL) is 1,641 nucleotides long and is capable of
      encoding a protein of 57.8 kDa. Northern (RNA blot) analysis demonstrated the
      presence of a high level of groE mRNA in exponential-phase H. ducreyi grown in
      hemin broth at the organism's optimal growth temperature (33 degrees C), with
      increased levels seen following heat shock. Heat shock also increased the
      thermostability of the organisms, since stressed cells were more resistant to the
      lethal effects of rapid chilling. Electrophoretic analysis and immunoblots
      demonstrated that the predominant protein produced by exponential-phase H.
      ducreyi was a heat-inducible, immunoreactive protein of approximately 60 kDa
      (GroEL). Also, H. ducreyi groE mRNA and GroEL were expressed and inducible by
      heat in E. coli. This is the first report describing the cloning, sequencing, and
      expression of H. ducreyi protein-encoding genes.

PMID- 1356927
TI  - Analysis of expression of toxin-coregulated pili in classical and El Tor Vibrio
      cholerae O1 in vitro and in vivo.
AB  - The expression of toxin-coregulated pili (TCP) and their structural subunit TcpA
      was compared in 20 strains of Vibrio cholerae of the classical and El Tor
      biotypes. Bacteria were isolated from the intestines of rabbits with experimental
      cholera and compared with the same strains grown under optimal TCP expression
      conditions in vitro. Immunoblotting revealed that TcpA production was induced in
      both biotypes after vibrios entered the intestinal milieu; TcpA-negative inocula
      gave rise to TcpA-positive vibrios after multiplication in the gut. The levels of
      TcpA expressed during growth in the intestine were, for most strains, comparable
      to those attained under optimal growth conditions in vitro. Of 11 classical
      strains tested, 10 expressed TCP antigen on the bacterial surface at levels
      comparable to or exceeding those seen after growth in vitro as determined by an
      inhibition enzyme-linked immunosorbent assay. In contrast, only one of the nine
      El Tor strains studied produced detectable amounts of TCP surface antigen in vivo
      and no fimbriae or surface antigen reacting with anti-TCP serum was found on El
      Tor vibrios from human cholera stools. Distinct TCP fimbriae were observed by
      immunoelectron microscopy on classical-biotype vibrios grown either in rabbit
      intestines or in vitro but were not detected on El Tor vibrios. The results show
      that TCP is expressed on V. cholerae O1 of the classical biotype but not on V.
      cholerae O1 of the El Tor biotype in the intestines of rabbits with experimental
      cholera infection.

PMID- 1356928
TI  - Adhesin presentation in bacteria requires molecular chaperones and ushers.

PMID- 1356929
TI  - Effect of ingested pentoxifylline on neutrophil superoxide anion production.
AB  - Superoxide and other oxygen radicals produced by activated polymorphonuclear
      leukocytes (PMN) may be important causes of tissue damage in a number of
      inflammatory conditions. Therefore, a drug which suppresses PMN responses in vivo
      is potentially important. In vitro, pentoxifylline (PTOX) inhibits superoxide
      anion production when PMN are stimulated with an activated complement component
      (C5a Des Arg) or formyl peptides but only at concentrations not achieved in the
      circulation. The aim of this study was to determine whether PTOX has an effect on
      PMN responses in vivo. Superoxide anion production, monitored by lucigenin
      enhanced chemiluminescence, was inhibited by 40.5% +/- 8.0% (n = 8, P < 0.009)
      for C5a Des Arg and 47.7% +/- 9.6% (n = 8, P < 0.009) for formyl
      methionylleucylphenylalanine stimulation 1.5 h after ingestion of 400 mg of PTOX
      in a slow-release tablet, with some inhibitory effects persisting at 5 h. There
      was a strong correlation between reduced PMN response to activated complement and
      plasma concentrations of three PTOX metabolites (P < 0.05), but not with plasma
      concentrations of the parent drug. In vitro investigations with each of the four
      methylxanthines showed two of these metabolites to be most effective at reducing
      PMN respiratory burst activity, lactoferrin release, and the expression of CD11b
      and CD18 molecules. Furthermore, this in vitro inhibitory activity was achieved
      at concentrations of metabolites achievable in vivo. The results suggest that
      PTOX reduces oxygen radical production and protects against unwanted tissue
      damage in vivo by the action of its metabolites.

PMID- 1356930
TI  - Functional heterogeneity of type 1 fimbriae of Escherichia coli.
AB  - Escherichia coli and other members of the family Enterobacteriaceae express
      surface fibrillar structures, fimbriae, that promote bacterial adhesion to host
      receptors. Type 1 fimbriae possess a lectinlike component, FimH, that is commonly
      thought to cause binding to mannose-containing oligosaccharides of host
      receptors. Since adhesion of type 1 fimbriated organisms are inhibited by
      mannose, the reactions are described as mannose sensitive (MS). We have studied
      the adhesion of the type 1 fimbriated CSH-50 strain of E. coli (which expresses
      only type 1 fimbriae) to fibronectin (FN). E. coli CSH-50 does not bind
      detectable amounts of soluble FN but adheres well to immobilized plasma or
      cellular FN. This adhesion was inhibited by mannose-containing saccharides. By
      using purified domains of FN, it was found that E. coli CSH-50 adheres primarily
      to the amino-terminal and gelatin-binding domains, only one of which is
      glycosylated, in an MS fashion. Binding of the mannose-specific lectin
      concanavalin A to FN and ovalbumin was eliminated or reduced, respectively, by
      incubation with periodate or endoglycosidase. Adhesion of E. coli CSH-50 to
      ovalbumin was reduced by these treatments, but adhesion to FN was unaffected. E.
      coli CSH-50 also adheres to a synthetic peptide copying a portion of the amino
      terminal FN domain (FNsp1) in an MS fashion. Purified CSH-50 fimbriae bound to
      immobilized FN and FNsp1 in an MS fashion and inhibited adhesion of intact
      organisms. However, fimbriae purified from HB101 (pPKL4), a recombinant strain
      harboring the entire type 1 fim gene locus and expressing functional type 1
      fimbriae, neither bound to FN or FNsp1 nor inhibited E. coli adhesion to
      immobilized FN or FNsp1. These novel findings suggest that there are two forms of
      type 1 MS fimbriae. One form exhibits only the well-known MS lectinlike activity
      that requires a substratum of mannose-containing glycoproteins. The other form
      exhibits not only the MS lectinlike activity but also binds to nonglycosylated
      regions of proteins in an MS manner.

PMID- 1356931
TI  - Dissemination of enteric Mycobacterium avium infections in mice rendered
      immunodeficient by thymectomy and CD4 depletion or by prior infection with murine
      AIDS retroviruses.
AB  - This study shows that infection of mice with the murine AIDS virus LP-BM5 or Du5H
      profoundly depressed the capacity of splenic T cells from these animals to
      respond to the T-cell mitogen phytohemagglutinin or concanavalin A or to
      alloantigens. Similar effects were also observed if mice were thymectomized and
      then infused with monoclonal anti-CD4 antibody (TxCD4- mice). When such mice were
      infected intravenously with Mycobacterium avium, growth of the infection was
      markedly exacerbated in the TxCD4- mice or in mice given murine AIDS virus 2
      months earlier. In view of these data, we then investigated whether such
      treatments might cause dissemination of M. avium following enteric implantation
      of bacteria into the mouse cecum; this route was chosen in an attempt to model
      events in AIDS patients, in which the gut appears to be one of the major portals
      of M. avium infection. In this model, the entry and hematogenous dissemination of
      four clinical isolates of M. avium were monitored against time and found to be
      accelerated and enhanced in T-cell-deficient mice. In view of this finding, these
      novel approaches for enteric infection that use immunodeficient mice are
      presented as potential new models for the evaluation of immunotherapy and
      chemotherapy in a setting that bears some similarity to events believed to occur
      in AIDS patients.

PMID- 1356932
TI  - Evaluation of genetic divergence among Borrelia burgdorferi isolates by use of
      OspA, fla, HSP60, and HSP70 gene probes.
AB  - In order to assess the genetic variation of immunologically relevant structures
      among isolates of the Lyme disease spirochete, Borrelia burgdorferi, three
      chromosomal genes encoding flagellin (fla) and the heat shock proteins HSP60 and
      HSP70, as well as the plasmid gene encoding outer surface protein A (OspA), from
      55 different European and North American strains obtained from ticks and mammal
      hosts have been investigated by restriction fragment length polymorphisms
      (RFLPs). RFLPs of fla and the HSP60 and HSP70 genes revealed two distinct banding
      patterns (A and B) for each of the three genes and allowed the definition of four
      genomic groups [AAA, BBB, BBA, and B(A/B)A] for the three chromosomal genes. On
      the other hand, RFLPs of the OspA gene revealed six distinct banding patterns
      (types I to VI) making up six independent genomic groups for the plasmid-encoded
      gene. Furthermore, we have sequenced the chromosomal HSP60 gene from B.
      burgdorferi ZS7 and the plasmid-encoded OspA gene from two strains, ZQ1 and
      19857. Alignment of the deduced HSP60 amino acid sequence from B. burgdorferi ZS7
      (genomic group AAA) to a previously published HSP60 sequence derived from strain
      ACA-1, which according to the proposed classification is in a different genomic
      group (BBA), revealed a sequence identity of > 99%. Similar alignments of the
      OspA sequence of strain ZQ1 to those of other isolates that were published
      previously revealed sequence identities of between 70 and 94% among strains of
      distinct OspA genomic groups. These data indicate the existence of a restricted
      number of species-specific subgroups and clearly show that genotypic variation is
      much more pronounced for the OspA gene than for fla and the HSP60 and HSP70
      genes. A phylogenetic tree constructed on the basis of distance matrix analyses
      of 12 OspA sequences supports the proposed classification of genomic groups of B.
      burgdorferi.

PMID- 1356933
TI  - Gamma interferon modifies CD4+ subset expression in murine candidiasis.
AB  - A single injection of monoclonal antibody to gamma interferon administered in
      conjunction with a live Candida albicans yeast cell vaccine resulted in the
      detection of nonprotective Th2 rather than protective Th1 responses and altered
      the early expression of interleukin 4 and gamma interferon mRNA in CD4+ cells.

PMID- 1356935
TI  - Strong induction of ICAM-1 in human T cells transformed by human T-cell-leukemia
      virus type 1 and depression of ICAM-1 or LFA-1 in adult T-cell-leukemia-derived
      cell lines.
AB  - Sixteen human T-cell lines were studied for the expression of a cell-adhesion
      molecule ICAM-1 and its counter-receptor LFA-1. The cell lines included 3 human T
      cell-leukemia-virus-type-I (HTLV-1)-negative cell lines derived from acute
      lymphoblastic leukemia (ALL) and 13 HTLV-1-positive cell lines, 7 of them
      established from cord- or peripheral-blood T cells by in vitro transformation
      with HTLV-1, 2 derived from HTLV-1 carriers, and 4 derived from patients with
      adult T-cell leukemia (ATL). In sharp contrast to a basal level of ICAM-1 in 3
      HTLV-1-negative ALL cell lines, strong induction of ICAM-1 was seen in all HTLV-1
      positive T-cell lines except for MT-1, one of the 4 ATL cell lines used in the
      present study. On the other hand, the expression of LFA-1 (CD11a and CD18) was
      more or less similar among the cell lines with and without HTLV-1. Interestingly,
      however, 3 out of 4 ATL cell lines (TL-Om1, H582, HUT102) revealed striking
      depression of LFA-1 expression. Several lines of evidence strongly argued against
      direct involvement of the viral transactivator p40tax or some autocrine cytokines
      in the induction of ICAM-1 in HTLV-1-positive T-cell lines. It was also found
      that ICAM-1 and LFA-1 were involved in syncytium formation induced in the co
      culture of HTLV-1-positive and HTLV-1-negative human T-cell lines. Implications
      of constitutive expression of ICAM-1 for certain clinical manifestations of ATL
      and of depression of either ICAM-1 or LFA-1 during progression of ATL are
      discussed.

PMID- 1356934
TI  - Protection against Vibrio cholerae El Tor infection by specific antibodies
      against mannose-binding hemagglutinin pili.
AB  - Both specific polyclonal antiserum and monoclonal antibodies against mannose
      binding hemagglutinin fimbriae of Vibrio cholerae (mannose-sensitive
      hemagglutinin [MSHA]) were shown to protect against experimental cholera caused
      by vibrios of the El Tor biotype in the infant mouse and in the rabbit intestinal
      loop models. MSHA-specific Fab immunoglobulin fragments were also protective. No
      protective effect was observed against challenge with V. cholerae O1 of the
      classical biotype. These results suggest that MSHA pili play an important role in
      the pathogenesis of cholera caused by the El Tor biotype of V. cholerae and that
      induction of intestinal anti-MSHA immunity may be a worthwhile additional
      objective in the development of oral cholera vaccines.

PMID- 1356936
TI  - Drugs, music, and ideology: a social pharmacological interpretation of the Acid
      House Movement.
AB  - During the summer of 1988, a musical concert experience called Acid House arrived
      on the cultural scene in many British cities. The media created a frenzy of
      misinformation in reporting about the latest drug craze. Acid House music was
      then banned from the pop music charts, radio and television, and retail outlets.
      Some psychoactive substances have been bought, sold, and consumed at Acid House
      events, but drug use does not appear to be extensive. At the physiological level,
      the nature of Acid House music, especially the drumming aspect, seems
      instrumental in providing altered states of consciousness. At the interpersonal
      and social level, the set and setting of Acid House events further enhances and
      reinforces the specific physiological and psychological responses. The degree of
      acceptance by various subcultural groups may depend greatly on the amount of
      media and societal exposure given to it, particularly if authoritarian attempts
      to suppress it enhance its political or ideological aspects.

PMID- 1356937
TI  - EUROMAC. A European Concerned Action: Maternal alcohol consumption and its
      relation to the outcome of pregnancy and child development at 18 months.

PMID- 1356938
TI  - Immunolocalization of epidermal growth factor receptor and c-erbB-2 oncogene
      product in human ovarian carcinoma.
AB  - Abnormalities of epidermal growth factor receptor (EGFR) and c-erbB-2 have been
      demonstrated to be correlated with aggressive biologic behavior in a variety of
      human cancers. To analyze the possible roles of these oncogenes in ovarian
      neoplasms, immunolocalization of EGFR and c-erbB-2 oncogene product was performed
      in 45 cases of human ovarian mucinous and serous cystadenomas, carcinomas of low
      malignant potential (LMP), and invasive carcinomas by employing antibodies
      against these oncogene products. EGFR immunoreactivity was present in 15 of 35
      LMP and invasive carcinomas and 1 of 10 cystadenomas. On the contrary,
      immunoreactivity of p185, which is an oncogene product of c-erbB-2, was detected
      only in five cases of carcinoma and in no benign cystadenoma. These results
      indicate that EGFR may be involved in the neoplastic process in epithelial
      ovarian adenocarcinoma, especially mucinous carcinoma, but involvement of c-erbB
      2 is probably not as prevalent as considered previously. Four of the five cases
      immunohistochemically positive for p185 were also positive for EGFR, which
      suggests that expression of EGFR and p185 is to some extent correlated in human
      ovarian carcinoma.

PMID- 1356939
TI  - Metabolic effects of three weeks administration of the beta-adrenoceptor agonist
      BRL 26830A.
AB  - BRL 26830A is a thermogenic beta-adrenergic agonist drug which has an anti
      obesity effect in animals and diet-restricted obese man. This study was
      undertaken in obese subjects who were not calorie restricted to assess the effect
      of three weeks drug administration on energy expenditure and glucose, amino acid
      and fatty acid metabolism in the post-absorptive and fed states. Stable isotope
      tracers were employed to determine kinetic data both at baseline and during
      adrenaline infusion. There was no evidence of BRL 26830A causing a major shift in
      fuel metabolism or having an anabolic effect. Baseline plasma concentrations of
      glycerol (P less than 0.01) and palmitate (P less than 0.01) were reduced,
      glucose remained within the normal range, whereas insulin decreased after BRL
      26830A. The hypoaminoacidaemic effect of adrenaline was attenuated by BRL 26830A
      (P less than 0.01 for branched-chain amino acids, P less than 0.05 for total
      amino acids). The results suggest that BRL 26830A improves insulin sensitivity
      and causes selective down-regulation of adrenergic receptors. The increased
      insulin sensitivity may be a useful therapeutic effect for this class of drug and
      suggests a possible role in the treatment of obese non-insulin dependent diabetic
      patients.

PMID- 1356940
TI  - Host association and the capacity of sand flies as vectors of lizard malaria in
      Panama.
AB  - In this paper the capacity of sand flies (Lutzomyia) as vectors of parasites that
      cause malaria in anoles (Anolis limifrons) in the Zona de Canal, Panama was
      investigated. Inhabiting all study plots, often in local abundance, L.
      trinidadensis emerged as the principal candidate sand fly vector; the results of
      surveys did not suggest a likely mosquito vector. Although L. trinidadensis and
      infected anoles co-inhabited all plots, their abundances seemed unrelated. No
      evidence that sand flies parasitized anoles was uncovered. As anole activity
      patterns in daylight reciprocate with those of sand flies and at night anoles
      seem to avoid locations that sand flies frequent, anoles may evade sand fly bites
      altogether. Further, these sand flies occurred in close numerical and ecological
      association with Thecadactylus rapicauda, a reclusive moist forest gecko, often
      parasitizing these hosts in large numbers. Thus, sand flies lack capacity as
      vectors of malaria-causing parasites in central Panamanian anoles.

PMID- 1356941
TI  - Isolation of a heptapeptide Val-Val-Tyr-Pro-Trp-Thr-Gln (valorphin) with some
      opiate activity.
AB  - Bovine hypothalamic tissue was extracted and purified by solid phase extraction
      and several reversed-phase HPLC steps. The amino acid sequence of the purified
      peptide was determined by Edman degradation to be Val-Val-Tyr-Pro-Trp-Thr-Gln.
      This was confirmed by comparison of its chromatographic behavior with that of the
      synthetic peptide, and mass spectrometric analysis resulted in a mass identical
      to the calculated mass for this peptide. This heptapeptide shows homology with
      residues 32-38 of the beta-chain of bovine hemoglobin. The peptide inhibited the
      electrically induced contractions of the guinea pig ileum muscle preparation;
      this inhibition was reversible by naloxone. It also inhibited the binding of 125I
      DAMGO (selective for mu receptors) to rat brain with an IC50 of 10 microM and the
      binding of 3H-DPDPE (selective for sigma receptors) with an IC50 of 185 microM.
      With two valines at the N-terminus and some opiate activity, valorphin seems a
      suitable name for this newly isolated peptide.

PMID- 1356943
TI  - [Beta blocker therapy. New aspects--outdated opinions. Interview by G. Riecker].

PMID- 1356942
TI  - [Aortic insufficiency with signs of inflammation and negative blood cultures].

PMID- 1356944
TI  - Histamine H1 receptor-mediated Ca2+ signaling in cultured bovine corneal
      endothelial cells.
AB  - The corneal endothelium pumps ions and water from the stroma to the aqueous
      humor, maintaining corneal transparency. This report investigates the possibility
      that cultured corneal endothelial cells express neurohormonal Ca2+ signaling
      pathways employed by other epithelia to regulate transport or other cellular
      functions. Agonist-stimulated changes in intracellular calcium ([Ca2+]i) in
      single bovine corneal endothelial cells (BCEC) derived from confluent cultures
      were measured by microspectrofluorimetry using the Ca(2+)-sensitive probe, fura
      2. Mean resting [Ca2+]i in BCEC was 46 +/- 2 nM (n = 124). The muscarinic
      cholinergic agonist, carbachol, did not mobilize Ca2+, whereas histamine induced
      a rapid increase in [Ca2+]i to initial peak levels of 549 +/- 22 nM (n = 46) at
      maximally stimulating doses. The initial rise in [Ca2+]i in response to histamine
      was dose dependent, with a minimum effective dose of 50 nM, EC50 = 0.84 mumol/l,
      and a maximum effective dose of 10 mumol/l. [Ca2+]i decreased from the initial
      peak, but then stabilized to form an agonist-dependent sustained elevation or
      abruptly fell back to baseline to begin oscillatory fluctuations. The initial
      peak was insensitive to removal of extracellular calcium (Ca2+o), whereas
      subsequent elevations in [Ca2+]i or sustained [Ca2+]i oscillations required
      Ca2+o. The amplitude of the oscillations in [Ca2+]i increased with an increase in
      [histamine]. However, frequency was independent of [histamine] (mean = 0.62
      spikes min-1 +/- 0.06, n = 33). Histamine-induced Ca2+ mobilization was inhibited
      by the H1 receptor antagonist triprolidine, but was unaffected by ranitidine (H2
      antagonist) or thioperamide (H3 antagonist).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1356945
TI  - RFLP analysis in the TNF-beta gene and the susceptibility to alloreactive NK
      cells in Behcet's disease.
AB  - Behcet's disease is known to be associated with HLA-B51. To address the
      possibility that a non-human leukocyte antigen (HLA) gene closely linked to the
      HLA-B gene, such as tumor necrosis factor (TNF)-alpha, TNF-beta, or ECl (the
      locus that determines the susceptibility to alloreactive natural killer [NK]
      cells), is involved in the susceptibility to Behcet's disease, NcoI and EcoRI
      restriction fragment length polymorphisms in the TNF-beta gene and the
      susceptibility to lysis by alloreactive NK cells were investigated in Behcet's
      patients. In our NcoI restriction fragment length polymorphism (RFLP) analysis in
      the TNF-beta gene, the frequency of the NcoI 5.5 kb homozygote was decreased
      considerably in the patients, especially those with the ocular lesions, in
      relation to the healthy controls. However, no significant difference was observed
      between these groups in the EcoRI RFLP band distribution in this gene or the in
      susceptibility to lysis by alloreactive NK cells. These results indicated that a
      non-HLA gene located around the TNF gene region centromic of the HLA-B gene was a
      candidate to control the genetic susceptibility to Behcet's disease.

PMID- 1356946
TI  - Do alpha-adrenergic receptors participate in control of the circadian rhythm of
      IOP?
AB  - The alpha 2-adrenergic antagonists, yohimbine and rauwolscine, and the alpha 1
      adrenergic antagonist, bunazosin, were used to explore the role of alpha
      adrenergic receptors in the regulation of the circadian rhythms of intraocular
      pressure and aqueous flow in New Zealand white rabbits. Blockade of alpha 2
      adrenergic receptors with yohimbine or rauwolscine produced small decreases in
      intraocular pressure during both light and dark phases. Rauwolscine had no effect
      on aqueous flow during the light or dark, but it increased the concentration of
      norepinephrine in the aqueous during both light and dark. These observations are
      difficult to reconcile with earlier suggestions that increased sympathetic input
      to the eye increases intraocular pressure and aqueous flow during the dark. The
      role of alpha 2-adrenergic receptors in the control of the circadian rhythm of
      intraocular pressure is unclear. Blockade of alpha 1-adrenergic receptors with
      bunazosin produced a dose-dependent reduction of IOP during the dark phase of the
      circadian cycle, a smaller reduction during the light phase, and no reduction
      during either light or dark in rabbits after superior cervical ganglionectomy or
      preganglionic section of the cervical sympathetic trunk (decentralization).
      Bunazosin decreased pupil diameter during the dark phase but had no effect on
      aqueous flow. Because it is unlikely that alpha 1-adrenergic blockade increased
      outflow facility or uveoscleral outflow, the mechanism for the role of alpha 1
      adrenergic receptors in the control of the circadian rhythm of intraocular
      pressure in rabbits remains to be identified.

PMID- 1356947
TI  - Pharmacologic management of aggression and violence.
AB  - The author discusses the differential diagnosis of violent and aggressive
      behavior, traditional and alternative treatments and OBRA-90 legislation.

PMID- 1356948
TI  - Primary biliary cirrhosis in Israel.
AB  - Primary biliary cirrhosis (PBC) is a relatively rare autoimmune disorder leading
      to the destruction of the interlobular biliary epithelium, which has not been
      reported in the Middle East. We studied 30 patients with PBC who had been
      referred to the Liver Unit at the Hadassah Medical Center in Jerusalem. The
      diagnosis was established by conventional criteria in 28 female and 2 male
      patients. Twenty-two patients were of Ashkenazic origin and 8 of Sephardic
      background. Mean serum alkaline phosphatase activity at the time of diagnosis was
      911 IU/l gamma-glutamyl transpeptidase 677 u/l, cholesterol 73 mmol/l, albumin
      3.2 g/l, bilirubin 72 mmol/l, and prothrombin time was 65%. All patients had
      positive antimitochondrial and M2 antibodies, and the mean IgM level was 684
      mg/dl. The diagnosis was confirmed by liver biopsy in 27 of 30 patients. To the
      best of our knowledge this represents the first report of primary biliary
      cirrhosis in the Jewish population in Israel. This retrospective survey raises
      the question whether the disease is indeed rare in Israel or, alternatively is
      underdiagnosed.

PMID- 1356949
TI  - The current value of exercise testing soon after acute myocardial infarction.
AB  - We performed exercise testing in 236 of 289 survivors of acute myocardial
      infarction to test the hypothesis that exercise-related parameters contribute to
      cardiac prognosis. Beta-blockers and/or calcium antagonists were used by 50% and
      55% respectively of the study population. Of the 236 patients 67 had received
      thrombolytic therapy during the acute event. By either univariate or multivariate
      analysis, we found that exercise-related parameters were poor predictors of
      cardiac prognosis. Therefore, in our population, exercise testing performed 3
      weeks after myocardial infarction provides little information of prognostic
      value.

PMID- 1356950
TI  - The autosomal dominant polycystic kidney disease gene in a Jewish family from
      Uzbekistan is PKD1.
AB  - A large Jewish family from Tashkent (Uzbekistan) was studied for linkage of
      autosomal dominant polycystic kidney disease (ADPKD) to molecular markers on the
      short arm of chromosome 16. A restriction fragment length polymorphism (RFLP)
      analysis was performed on 28 family members, including 9 ADPKD diagnosed patients
      in 3 consecutive generations. A specific haplotype was found to segregate with
      the disease in eight of the nine affected individuals. The peak lod scores for
      linkage between the disease phenotype and the five informative flanking markers
      were: 3'HVR 1.70 at theta = 0.08; GGG1 1.18 at theta = 0.001; CMM65 1.50 at theta
      = 0.001; 26-6 0.86 at theta = 0.001 and 218EP6 1.39 at theta = 0.001. A
      particular haplotype of these markers segregated with the disease phenotype. The
      peak lod score of this haplotype was 3.046. Homogeneity test, comparing this
      family to 40 PKD European families, showed that the conditional probability that
      it belongs to the same group is 1.000. Taken together, these findings show that
      the defective gene in this Jewish family from Uzbekistan is PKD1. To our
      knowledge, this is the first ADPKD family in Israel in whom linkage studies were
      performed and one of the few originating from populations outside the Western
      world.

PMID- 1356951
TI  - Summary statements from the Third Conference on Radiation Protection and
      Dosimetry.
AB  - The Third Conference on Radiation Protection and Dosimetry was conducted in
      Orlando, FL, on 21-24 October 1991. At the end of the conference, each member of
      the Technical Program Committee summarized the events considered to be of
      particular importance. Subjects discussed included dosimetry accreditation
      programs, regulations, standards, compliance, advances in dosimeters and
      instrumentation, training, needs in metrology, and funding of dosimetry research.
      These statements have been collected and combined and are presented as a brief
      summary of the conference.

PMID- 1356952
TI  - Preparation and in vivo binding of [11C]carazolol, a radiotracer for the beta
      adrenergic receptor.
AB  - Carazolol is a high affinity beta-adrenergic receptor antagonist which is
      relatively non-specific for the receptor subtypes. The labeling of the two
      enantiomers of this compound with carbon-11, including the synthesis of the
      required labeling precursors, is reported. The yield and specific activity are
      sufficient for use in positron tomography. Biodistribution and specific receptor
      binding studies show the labeled material to be of interest for further
      investigation as a radiopharmaceutical for positron tomography.

PMID- 1356953
TI  - Suitability of CGP-12177 and CGP-26505 for quantitative imaging of beta
      adrenoceptors.
AB  - [3H]CGP-12177, a non-selective beta-adrenoceptor antagonist, and [3H]CGP-26505, a
      beta 1-selective beta-adrenoceptor antagonist, were intravenously administered to
      rats. 94-97% of the injected radioactivity disappeared from plasma with t1/2 0.2
      and 0.5 min. Total/non-specific binding ratios of 5.4 and 6.9 (CGP-12177) or 2.0
      and 2.8 (CGP-26505) were maintained in heart and lung from 10 to 40 min post
      injection. Labelled plasma metabolites appeared after greater than 20 min (CGP
      12177) or within 2 min (CGP-26505). No metabolites were found in the heart. CGP
      12177 binds to blood cells, but CGP-26505 does not. CGP-12177 can be used for PET
      imaging of total (beta 1 and beta 2) adrenoceptors in the heart and lung of
      experimental animals, but CGP-26505 is less suitable for in vivo analysis of the
      beta 1-subpopulation.

PMID- 1356954
TI  - HLA genotyping of colorectal carcinoma in the Chinese population.
AB  - The HLA-DR genotypes of 61 primary colorectal carcinomas obtained from patients
      of Chinese origin were determined by using DNA-RFLP. No increase or decrease of a
      particular HLA genotype could be ascertained with the disease, although we
      detected an antigen frequency of 29.5% for the serologically ill-defined DR"X3"
      specificity. We identified and sequenced HLA-DRB1 and DRB3 genes from the DR"X3"
      haplotype. The DR"X3" DRB1 gene was found to be identical to DRB1*1201
      (DR5[w12]). A unique observation is its unusual linkage with DRB3*0101 (DRw52a)
      or DRB3*0301 (DRw52c) instead of the usual linkage with DRB3*0201/2 (DRw52b).
      These associations are rare in whites and blacks.

PMID- 1356955
TI  - Complexity of the HLA-DP region: RFLP analysis versus PLT typing and oligotyping.
AB  - A total of 84 individuals were DP typed in parallel with the restriction fragment
      length polymorphism (RFLP) analysis and the primed lymphocyte test (PLT). Whereas
      80% of the cases gave concordant results, the other 20% showed discrepancies for
      one of the two alleles carried by the typed individuals. Oligotyping, PCR-RFLP
      and sequencing confirmed the results found by PLT. The 20% discordant results
      obtained with RFLP led us to conclude that RFLP typing cannot replace PLT typing.
      From a more general point of view, the RFLP analysis revealed the DP region to be
      more complex than expected since for each given PLT DP defined specificity, more
      than one RFLP DP haplotype could be determined. These were possibly induced by
      crossing-overs or gene conversion events.

PMID- 1356956
TI  - HLA class II frequencies in celiac disease patients in the west of Ireland.
AB  - Restriction fragment length polymorphism analysis, using a single restriction
      enzyme TaqI-multiple-probe system for HLA-DRB1-DQB1 and -DQA1, was used to
      determine HLA-DR and -DQ frequencies in 56 unrelated celiac patients and 47
      unrelated controls from the west of Ireland. In addition, HLA-DPB1 allelic
      frequencies were determined in the same group of patients and controls by using
      the technique of enzymatic DNA amplification of the polymorphic second exon of
      HLA-DPB1 genes in conjunction with sequence-specific oligonucleotide probing. The
      results suggest that HLA-DQ rather than HLA-DR is more important in conferring
      susceptibility to celiac disease. Furthermore, no association between HLA-DP and
      celiac disease was found in this study.

PMID- 1356957
TI  - Identification of the HLA-DRB1*04, -DRB1*07, and -DRB1*09 alleles by PCR
      amplification with sequence-specific primers (PCR-SSP) in 2 hours.
AB  - The clinical applicability of genomic HLA class II typing techniques has
      increased after the introduction of PCR-based typing strategies. In typing by PCR
      amplification using sequence-specific primers (PCR-SSP), amplification of
      specific alleles or groups of alleles is achieved, provided that the mismatch(es)
      of the SSP is located in the 3' end of the primer. Thus, the specificity of the
      typing system becomes part of the amplification step, which reduces the total
      typing time to a minimum by simplifying the postamplification processing of
      samples. The set of primers presented here identifies all of the alleles of the
      DR4 group, DRB1*0401-DRB1*0411, as well as the DRB1*07 and DRB1*0901 alleles. In
      the present study of DR4 alleles, PCR-SSP was compared with hybridization with
      sequence-specific oligonucleotide probes following group-specific PCR
      amplification (PCR-SSO). The two typing strategies gave completely concordant
      results in the 90 DR4-positive and the 32 DR4-negative individuals and cell lines
      studied. DR7,DQ9/DR9,DQ9 discrimination using PCR-SSP, was compared with MspI DQA
      RFLP typing, also with concordant results in the 33 DR7- and/or DR9-positive and
      36 DR7- and DR9-negative individuals and cell lines tested. No false-negative or
      false-positive typing results were obtained. Genomic typing by PCR-SSP was
      performed in the overall time of 2 hours, including rapid DNA preparation, PCR
      amplification, postamplification processing, documentation, and interpretation of
      results. This makes the PCR-SSP strategy for HLA class II typing attractive not
      only in population- and disease-association studies, but also in routine clinical
      practice, including donor-recipient matching prior to cadaveric transplantation.

PMID- 1356958
TI  - Problem-based learning: an approach toward reforming allied health education.
AB  - Problem-based learning (PBL) is presented as a useful way to educate allied
      health practitioners for the future. The essential characteristics of problem
      based learning include: curricular organization around problems rather than
      disciplines; an integrated curriculum rather than one separated into clinical and
      theoretical components; and an inherent emphasis on cognitive skills as well as
      on knowledge. Long-term advocates of PBL stress that it is the only known method
      for preparing future professionals to be able to adapt to change, learning how to
      reason critically, enabling a holistic approach to health, and attaining
      integrated, cumulative learning.

PMID- 1356959
TI  - Estrogen receptor, c-erbB-2 and nm23/NDP kinase expression in the intraductal and
      invasive components of human breast cancers.
AB  - Expression of the c-erbB-2 oncoprotein (ErbB-2) and the nm23 anti-metastatic gene
      product (nucleoside diphosphate [NDP] kinase) was examined in the intraductal and
      invasive components of 63 fresh human breast cancer tissues. The expression of
      estrogen receptor (ER) as a marker of hormone dependency and the Ki-67 protein as
      a proliferative cell marker was also examined. ErbB-2 and ER were positive in
      77.8% (28/36) and 64.7% (22/34) of the intraductal components, and in 43.6%
      (27/62) and 57.1% (36/63) of the invasive components, respectively. NDP kinase
      was positive in 58% (18/31) of intraductal, and in 30.9% (17/55) of invasive
      areas. The average Ki-67-positive cell rates were 5.9% in the intraductal, and
      10.7% in the invasive components. Thus, the cells within the intraductal
      component of breast cancer appear to have different characteristics from the
      invasive component, not only in markers of proliferative ability, but also in the
      expression of oncogenes and hormone receptors.

PMID- 1356960
TI  - Biology of inherited coagulopathies: factor IX.
AB  - Characterization of the functional domains of FIX and related vitamin K-dependent
      proteins has been enhanced by the isolation and characterization of the genes
      encoding these proteins. A better understanding of the interactions between FIX's
      activators, cofactors, and substrate, FX, has been gained through the study of
      naturally occurring variants isolated from patients with hemophilia B and
      genetically engineered recombinant molecules. With the determination of specific
      mutations in hemophilia B kindreds, and through advances in molecular techniques,
      especially the polymerase chain reaction, more accurate determination of carrier
      status and prenatal diagnosis can now be made.

PMID- 1356962
TI  - The 10th International Conference of The Cardiovascular System Dynamics Society.
      Kobe, Japan, September 23-25, 1992. Abstracts.

PMID- 1356961
TI  - Pharmacological properties of alpha 1-adrenoceptor-mediated vasoconstrictions in
      dog and monkey lingual arteries: evidence for subtypes of alpha 1-adrenoceptors.
AB  - We examined whether alpha 1-adrenoceptor-mediated vasoconstrictions were due to
      extra- or intracellular Ca2+ movements, and whether they were subdivided into
      alpha 1-adrenoceptor subtypes in dog and monkey lingual arteries. The NE-induced
      vasoconstriction in dog lingual arteries was mostly dependent on Ca2+ influx from
      the extracellular space, since it was readily blocked by a Ca2+ entry blocker,
      diltiazem, and the NE-induced response was attenuated approximately 90% in Ca(2+)
      free solution. On the other hand, in monkey lingual arteries, diltiazem failed to
      depress the NE-induced dose-response curve, and the response was attenuated only
      about 60% in Ca(2+)-free solution. The vasoconstrictor response to 10mg caffeine
      in normal KHS was almost the same as that to 1 micrograms NE in Ca(2+)-free
      solution in both kinds of arteries, suggesting that alpha 1-adrenoceptor
      mediating vasoconstrictions require a different number of sources of Ca2+ in
      different blood vessels. Pretreatment of preparations with CEC (an alpha 1B
      antagonist) significantly suppressed and shifted the dose-response curve for NE
      to the right in monkey lingual arteries, but it had no significant effect in dog
      lingual arteries. However, WB4101 (an alpha 1A-antagonist) showed almost the same
      potency in blocking vasoconstrictor responses as bunazosin in both kinds of
      arteries (the pA2 values were not significantly different). Moreover, responses
      to ME (an alpha 1A-agonist) were blocked by diltiazem as well as by bunazosin and
      WB4101, while CEC had no blocking effect on ME-induced responses.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1356963
TI  - Characterization of the complex pdxH-tyrS operon of Escherichia coli K-12 and
      pleiotropic phenotypes caused by pdxH insertion mutations.
AB  - We report the first molecular genetic analysis of a pyridoxine 5'-phosphate
      oxidase, the PdxH gene product of Escherichia coli K-12. Chromosomal insertions
      in and around pdxH were generated with various transposons, and the resulting
      phenotypes were characterized. The DNA sequence of pdxH was determined, and the
      promoters of pdxH and the downstream gene tyrS, which encodes tyrosyl-tRNA
      synthetase, were mapped by RNase T2 protection assays of chromosomal transcripts.
      These combined approaches led to the following conclusions: (i) pdxH is
      transcribed from a sigma 70-type promoter and shares its transcript with tyrS;
      (ii) tyrS is additionally transcribed from a relatively strong, nonconventional
      internal promoter that may contain an upstream activating sequence but whose
      expression is unaffected by a fis mutation; (iii) PdxH oxidase is basic, has a
      molecular mass of 25,545 Da, and shares striking homology (greater than 40%
      identity) with the developmentally regulated FprA protein of Myxococcus xanthus;
      (iv) mild pyridoxal 5'-phosphate limitation of pdxH mutants inhibits cell
      division and leads to formation of unsegregated nucleoids; (v) E. coli PdxH
      oxidase is required aerobically and anaerobically, but second-site suppressors
      that replace pdxH function entirely can be isolated; and (vi) pdxH mutants
      excrete significant amounts of L-glutamate and a compound, probably alpha
      ketoisovalerate, that triggers L-valine inhibition of E. coli K-12 strains. These
      findings extend earlier observations that pyridoxal 5'-phosphate biosynthetic and
      aminoacyl-tRNA synthetase genes are often members of complex, multifunctional
      operons. Our results also show that loss of pdxH function seriously disrupts
      cellular metabolism in unanticipated ways.

PMID- 1356964
TI  - Role of phosphorylated metabolic intermediates in the regulation of glutamine
      synthetase synthesis in Escherichia coli.
AB  - Transcription of the Ntr regulon is controlled by the two-component system
      consisting of the response regulator NRI (NtrC) and the kinase/phosphatase NRII
      (NtrB), which both phosphorylates and dephosphorylates NRI. Even though in vitro
      transcription from nitrogen-regulated promoters requires phosphorylated NRI, NRII
      independent activation of NRI also occurs in vivo. We show here that this
      activation likely involves acetyl phosphate; it is eliminated by mutations that
      reduce synthesis of acetyl phosphate and is elevated by a mutation expected to
      cause accumulation of acetyl phosphate. With purified components, we investigated
      the mechanism by which acetyl phosphate stimulates glutamine synthetase
      synthesis. Acetyl phosphate, carbamyl phosphate, and phosphoramidate but not ATP
      or phosphoenolpyruvate acted as substrates for the autophosphorylation of NRI in
      vitro. Phosphorylated NRI produced by this mechanism exhibited the properties
      associated with NRI phosphorylated by NRII, including the activated ATPase
      activity of the central domain of NRI and the ability to activate transcription
      from the nitrogen-regulated glutamine synthetase glnAp2 promoter.

PMID- 1356965
TI  - Analysis of a peptidoglycan hydrolase gene from Staphylococcus aureus NCTC 8325.
AB  - We have investigated the expression of the peptidoglycan hydrolase gene (lytA) of
      Staphylococcus aureus NCTC 8325. Results from in vitro transcription-translation
      analysis, maxicell experiments, and Northern (RNA) blot analysis suggest that the
      lytA gene encodes a polypeptide of M(r) approximately 50,000. Physical mapping
      data indicate that the lytA gene originated from prophage 11 in the NCTC 8325
      strain.

PMID- 1356966
TI  - Murein-metabolizing enzymes from Escherichia coli: existence of a second lytic
      transglycosylase.
AB  - In addition to the soluble lytic transglycosylase, a murein-metabolizing enzyme
      with a molecular mass of 70 kDa (Slt70), Escherichia coli possesses a second
      lytic transglycosylase, which has been described as a membrane-bound lytic
      transglycosylase (Mlt; 35 kDa; EC 3.2.1.-). The mlt gene, which supposedly
      encodes Mlt, was cloned, and the complete nucleotide sequence was determined. The
      open reading frame, identified on a 1.7-kb SalI-PstI fragment, codes for a
      protein of 323 amino acids (M(r) = 37,410). Two transmembrane helices and one
      membrane-associated helix were predicted in the N-terminal half of the protein.
      Lysine and arginine residues represent up to 15% of the amino acids, resulting in
      a calculated isoelectric point of 10.0. The deduced primary structure did not
      show significant sequence similarity to Slt70 from E. coli. High-level expression
      of the presumed mlt gene was not paralleled by an increase in murein hydrolase
      activity. To clarify the identity of the second transglycosylase, we purified an
      enzyme with the specificity of a transglycosylase from an E. coli slt deletion
      strain. The completely soluble transglycosylase, with a molecular mass of
      approximately 35 kDa, was designated Slt35. Its determined 26 N-terminal amino
      acids showed similarity to a segment in the middle of the Slt70 primary
      structure. Polyclonal anti-Mlt antibodies, which had been used for the isolation
      of the mlt gene, were found to cross-react with Mlt as well as with Slt35,
      suggesting that the previously described Mlt preparation was contaminated with
      Slt35. We conclude that the second transglycosylase of E. coli is not a membrane
      bound protein but rather is a soluble protein.

PMID- 1356968
TI  - Identification and analysis of a genomic strain cluster of mycoplasmalike
      organisms associated with Canadian peach (eastern) X disease, western X disease,
      and clover yellow edge.
AB  - Genetic interrelatedness among 13 strains of mycoplasmalike organisms (MLOs) from
      various sources was evaluated by dot hybridization and restriction fragment
      length polymorphism analyses using cloned DNA probes derived from Canadian peach
      X (CX) and western X (WX) MLOs. Dot hybridization analysis indicated that CX, WX,
      and clover yellow edge MLOs are closely related and form a distinct strain
      cluster that is only distantly related to the 10 other MLOs. Similarity
      coefficients derived from restriction fragment length polymorphism analysis
      revealed that CX, WX, and clover yellow edge MLOs represent three distinct
      genomic types.

PMID- 1356967
TI  - Identification and molecular characterization of the acetyl coenzyme A synthetase
      gene (acoE) of Alcaligenes eutrophus.
AB  - The gene locus acoE, which is involved in the utilization of acetoin in
      Alcaligenes eutrophus, was identified as the structural gene of an acetyl
      coenzyme A synthetase (acetate:coenzyme A ligase [AMP forming]; EC 6.2.1.1). This
      gene was localized on a 3.8-kbp SmaI-EcoRI subfragment of an 8.1-kbp EcoRI
      restriction fragment (fragment E) that was cloned recently (C. Frund, H.
      Priefert, A. Steinbuchel, and H. G. Schlegel, J. Bacteriol. 171:6539-6548, 1989).
      The 1,983 bp acoE gene encoded a protein with a relative molecular weight of
      72,519, and it was preceded by a putative Shine-Dalgarno sequence. A comparison
      analysis of the amino acid sequence deduced from acoE revealed a high degree of
      homology to primary structures of acetyl coenzyme A synthetases from other
      sources (amounting to up to 50.5% identical amino acids). Tn5 insertions in two
      transposon-induced mutants of A. eutrophus, that were impaired in the catabolism
      of acetoin were mapped 481 and 1,159 bp downstream from the translational start
      codon of acoE. The expression of acoE in Escherichia coli led to the formation of
      an acyl coenzyme A synthetase that accepted acetate as the preferred substrate
      (100% relative activity) but also reacted with propionate (46%) and
      hydroxypropionate (87%); fatty acids consisting of four or more carbon atoms were
      not accepted. In addition, evidence for the presence of a second acyl coenzyme A
      synthetase was obtained; this enzyme exhibited a different substrate specificity.
      The latter enzyme is obviously required for the activation of propionate, e.g.,
      during the formation of the storage compound poly(3-hydroxybutyric acid-co-3
      hydroxyvaleric acid) when propionate is provided as the sole carbon source. An
      analysis of mutants provided evidence that the expression of the uptake protein
      for propionate depends on the presence of alternate sigma factor sigma 54.

PMID- 1356969
TI  - Two novel heat shock genes encoding proteins produced in response to heterologous
      protein expression in Escherichia coli.
AB  - In Escherichia coli high-level production of some heterologous proteins
      (specifically, human prorenin, renin, and bovine insulin-like growth factor 2)
      resulted in the induction of two new E. coli heat shock proteins, both of which
      have molecular masses of 16 kDa and are tightly associated with inclusion bodies
      formed during heterologous protein production. We named these inclusion body
      associated proteins IbpA and IbpB. The coding sequences for IbpA and IbpB were
      identified and isolated from the Kohara E. coli gene bank. The genes for these
      proteins (ibpA and ibpB) are located at 82.5 min on the chromosome. Nucleotide
      sequencing of the two genes revealed that they are transcribed in the same
      direction and are separated by 110 bp. Putative Shine-Dalgarno sequences are
      located upstream from the initiation codons of both genes. A putative heat shock
      promoter is located upstream from ibpA, and a putative transcription terminator
      is located downstream from ibpB. A temperature upshift experiment in which we
      used a wild-type E. coli strain and an isogenic rpoH mutant strain indicated that
      a sigma 32-containing RNA polymerase is involved in the regulation of expression
      of these genes. There is 57.5% identity between the genes at the nucleotide level
      and 52.2% identity at the amino acid level. A search of the protein data bases
      showed that both of these 16-kDa proteins exhibit low levels of homology to low
      molecular-weight heat shock proteins from eukaryotic species.

PMID- 1356971
TI  - A protease inhibitor produced by Streptomyces lividans 66 exhibits inhibitory
      activities toward both subtilisin BPN' and trypsin.
AB  - A proteinaceous protease inhibitor was isolated from the culture broth of
      Streptomyces lividans 66 by a series of purification steps (salting out by
      ammonium sulfate, ion-exchange chromatography on DEAE-cellulose, hydrophobic
      chromatography on Phenyl-Sepharose, and gel-filtration on Sephacryl S-200), and
      was named S. lividans protease inhibitor (SLPI). The purified SLPI existed in a
      dimeric form consisting of two identical subunits, each of which was composed of
      107 amino acids. SLPI exhibited strong inhibitory activity toward subtilisin
      BPN'. These features were similar to those of protein protease inhibitors
      produced by other Streptomyces (SSI family inhibitor). In addition, SLPI was
      capable of inhibiting trypsin with an inhibitor constant (Ki) of about 10(-9) M.
      The primary structure of SLPI and location of two disulfide bridges were
      homologous to those of the other serine protease inhibitors of Streptomyces. The
      reactive site of SLPI was found to be Arg67-Glu68 from the sequence analysis of
      cleaved SLPI which was produced by acidification of subtilisin-SLPI complex. An
      Arg residue at the P1 site was consistent with the trypsin-inhibitory property of
      SLPI. Sequence comparison with other members of the SSI family revealed that
      amino acid replacements in SLPI were mainly localized on the surface of the SLPI
      molecule, and many of the amino acid residues in beta-sheets and hydrophobic core
      were well conserved.

PMID- 1356972
TI  - Cross-linking of contractile proteins from skeletal muscle by treatment with
      microbial transglutaminase.
AB  - The action on muscle proteins of microbial transglutaminase (MTGase), which
      catalyzes the formation of a "zero-length" covalent cross-link between glutamine
      and lysine residues in peptides, was studied in order to define a basis for
      future application of MTGase cross-linking to the study of muscle protein
      interaction. We examined the cross-linking of skeletal muscle myosin, myosin
      subfragments, actin, and myofibrils by treatment with MTGase and the possible
      side-effects of the cross-linking on the enzymic activity of myosin, and found
      that the rod portions of myosin in myosin filaments were quickly cross-linked to
      each other by the action of MTGase, but myosin subfragment 1 was not cross-linked
      to actin. The MgATPase activities at 0.5 M KCl of myosin, heavy meromyosin,
      subfragment 1, and subfragment 1-actin were not significantly affected by the
      MTGase reaction. A very small fraction of the head portion of heavy meromyosin
      was cross-linked to actin in their rigor complexes by MTGase, and the ATPase
      activity at 0.5 M KCl of the cross-linked heavy meromyosin-actin complexes was
      slightly enhanced.

PMID- 1356970
TI  - Thermoregulation of the pap operon: evidence for the involvement of RimJ, the N
      terminal acetylase of ribosomal protein S5.
AB  - Our previous work showed that pap pilin gene transcription is subject to a
      thermoregulatory control mechanism under which pap pilin is not transcribed at a
      low temperature (23 degrees C) (L. B. Blyn, B. A. Braaten, C. A. White-Ziegler,
      D. H. Rolfson, and D. A. Low, EMBO J. 8:613-620, 1989). In order to isolate genes
      involved in this temperature regulation of gene expression, chromosomal mini-Tn10
      (mTn10) mutations that allowed transcription of the pap pilin gene at 23 degrees
      C were identified, and the locus was designated tcp, for "thermoregulatory
      control of pap" (C. A. White-Ziegler, L. B. Blyn, B. A. Braaten, and D. A. Low,
      J. Bacteriol. 172:1775-1782, 1990). In the present study, quantitative analysis
      showed that the tcp mutations restore pap pilin transcription at 23 degrees C to
      levels similar to those measured at 37 degrees C. By in vivo recombination, the
      tcp mutations were mapped to phage E4H10S of the Kohara library of the
      Escherichia coli chromosome (Y. Kohara, K. Akiyama, and K. Isono, Cell 50:495
      508, 1987). The tcp locus was cloned by complementation, in which a 1.3-kb DNA
      fragment, derived from the Kohara phage, was shown to restore thermoregulation to
      the mTn10 mutants. DNA sequencing revealed two open reading frames (ORFs)
      encoding proteins with calculated molecular masses of 22.7 and 20.3 kDa. The
      sequence of the 22.7-kDa ORF was identical to that of rimJ, the N-terminal
      acetylase of the ribosomal protein S5. The gene encoding the 20.3-kDa ORF,
      designated g20.3 here, did not display significant homology to any known DNA or
      protein sequence. On the basis of Northern (RNA) blot data, rimJ and g20.3 are
      located within the same operon. Two of the mTn10 transposons in the
      thermoregulatory mutants were inserted within the coding region of rimJ,
      indicating that the RimJ protein plays an important role in the temperature
      regulation of pap pilin gene transcription. However, rimJ itself is not
      thermoregulated, since rimJ transcripts were detected at both 23 and 37 degrees
      C. Disruption of the g20.3 gene by insertion and deletion mutagenesis did not
      affect thermoregulation of the pap operon, suggesting that, although g20.3 lies
      within the same operon as rimJ, it does not play a role in thermoregulation.

PMID- 1356973
TI  - Effects of aging on gene expression of acetyl-CoA carboxylase and fatty acid
      synthase in rat liver.
AB  - After refeeding a fat-free diet to fasted rats, the time courses of
      transcriptional rates, mRNA concentrations, and enzyme induction of hepatic
      acetyl-CoA carboxylase and fatty acid synthase were compared between 1.5- and 18
      month-old rats. In the old rats, the levels were mostly 40-70% of those in the
      young animals. Moreover, the peaks of the levels tended to be delayed in the old
      animals. The transcriptional rates were increased within only 1 h after the
      refeeding in the young animals, but not until 6 h in the old. The mRNA
      concentrations reached maximum at 16 h in the young rats, but at 24 h in the old.
      In the old rats, the incorporation of [3H]leucine into the enzyme proteins was
      also decreased roughly in proportion to the enzyme induction. The mRNA
      concentrations in the liver polysomes were roughly proportional to the total
      mRNAs. Thus, the translational activities did not appear to be altered by aging.
      It is suggested that the age-dependent decreases of acetyl-CoA carboxylase and
      fatty acid synthase induction can be mainly ascribed to the transcriptional
      steps.

PMID- 1356974
TI  - Inhibition of T7 RNA polymerase by T7 lysozyme in vitro.
AB  - The in vivo observation that the expression of bacteriophage T7 gene 3.5 (T7
      lysozyme) inactivates T7 class II transcription and the in vitro observation that
      T7 lysozyme inhibits T7 RNA polymerase lead to the hypothesis that T7 lysozyme
      might preferentially inhibit transcription from T7 class II promoters. T7
      lysozyme was cloned into a lambda pL expression vector, overproduced in
      Escherichia coli, and purified. The ability of purified T7 lysozyme to inhibit
      transcription from T7 DNA, the cloned T7 class II promoters, phi 2.5 and phi 4.7,
      and the cloned class III promoter, phi 10, was measured in vitro. It was observed
      that the effectiveness of T7 lysozyme as an inhibitor of T7 RNA polymerase is
      inversely related to the concentration of Mg2+; T7 lysozyme inhibits T7 RNA
      polymerase most effectively at low Mg2+ concentrations. In addition, no
      preferential inhibition of transcription from cloned T7 class II promoters was
      observed, nor was a strong T7 class III promoter preferred when transcriptional
      capacity was reduced by T7 lysozyme. These observations contradict the hypotheses
      that the temporal control of T7 gene expression is either due to direct and
      selective inhibition of the T7 class II promoters by T7 lysozyme or to
      preferential transcription of the strong T7 class III promoters when
      transcriptional capacity is reduced by T7 lysozyme. It appears that alternative
      mechanisms such as the involvement of additional proteins and/or cellular
      conditions to enhance transcription from T7 class III promoters or to inhibit
      transcription from T7 class II promoter are necessary to explain the temporal
      control of transcription of bacteriophage T7.

PMID- 1356975
TI  - Transcriptional regulation by a point mutant of adenovirus-2 E1a product lacking
      DNA binding activity.
AB  - The adenovirus E1a protein (E1A) regulates transcription through interaction with
      transcription factors bound to DNA, like cAMP response element BP1/ATF2, or
      through dissociating E2F transcription factor complex. However, it was also
      reported that E1A can bind to DNA (Chatterjee, P. K., Bruner, M., Flint, S. J.,
      and Harter, M. L. (1988) EMBO J. 7, 835-841), and it is not clear whether DNA
      binding of E1A is involved in a part of the process of transcriptional regulation
      by E1A. In this paper, the small region of E1A that is responsible for DNA
      binding was identified and a point mutant lacking DNA binding activity was
      constructed. Analysis of deletion mutants of E1A proteins expressed in bacteria
      showed that a basic region between amino acids 201 and 216 of E1A is essential
      for DNA binding. Point mutation of arginines at amino acid numbers 205 and 206 to
      aspartic acids completely abolished the DNA binding activity of E1A. Using this
      mutant, the requirement of the E1A DNA binding for E1A-dependent transcriptional
      regulation was examined. trans-Activation of the adenovirus E4 promoter and trans
      repression of the human c-erbB-2 promoter by this point mutant were examined by
      cotransfection experiments. Mutations of the E1A DNA-binding domain affected
      neither the E1A-induced trans-activation nor trans-repression at all. These
      results give complete proof that the DNA binding activity of E1A is not required
      for transcriptional regulation by E1A.

PMID- 1356976
TI  - The human blood fluke Schistosoma mansoni synthesizes glycoproteins containing
      the Lewis X antigen.
AB  - Infection of vertebrates with the parasitic blood fluke Schistosoma mansoni
      induces a variety of host immune responses, which are directed against both
      protein and carbohydrate antigens. In this report, we describe our studies on the
      structures of antigenic oligosaccharides derived from glycoproteins synthesized
      by S. mansoni. Immobilized antibodies derived from the sera of infected hamsters
      and mice bind to a family of high molecular weight Asn-linked oligosaccharides in
      glycoproteins from the adult parasite. Structural analysis of the major antigenic
      oligosaccharides revealed that they have high amounts of fucose-linked alpha 1,3
      to N-acetylglucosamine residues within the linear repeating disaccharide (3Gal
      beta 1-4GlcNAc beta 1)n, a poly-N-acetyllactosamine sequence containing the Lewis
      X antigenic blood group. The remarkable ability of S. mansoni to synthesize these
      vertebrate-type oligosaccharides may have implications in both the mechanisms of
      host-parasite interactions and on the development of vaccines to prevent this
      disease in humans.

PMID- 1356977
TI  - The involvement of a LINE-1 element in a DNA rearrangement upstream of the mdr1a
      gene in a taxol multidrug-resistant murine cell line.
AB  - Two closely related but functionally distinct P-glycoprotein isoforms are encoded
      by the murine multidrug-resistance genes mdr1a and mdr1b. In a series of
      independently selected multidrug-resistant (MDR) J774.2 cell lines, mdr gene
      amplification and/or overexpression and overproduction of either the mdr1a or
      mdr1b products, or both gene products, correlates with the MDR phenotype. To
      investigate the possibility that mutations in the promoter regions of the mdr1a
      or mdr1b genes could influence their differential expression, mdr promoter
      specific probes were used to detect and map potential structural alterations. An
      unusual structural rearrangement was found in the 5'-region of the amplified
      mdr1a allele in J7.T1, a cell line selected with taxol. To characterize this
      rearrangement, the regulatory regions of the mdr1a and mdr1b genes were analyzed.
      Whereas no gross structural alterations were detected by Southern blot
      hybridization using the mdr1b promoter probe, a novel amplified EcoRI fragment
      was detected by the mdr1a promoter probe. To determine the precise nature of this
      mutation, an mdr1a 5'-genomic clone was isolated from J7.T1 cells. Sequence
      analysis revealed an unusual DNA rearrangement consisting of the mdr1b gene, from
      its fourth intron toward its 3'-end, upstream of an intact mdr1a promoter on the
      amplified allele. We propose that this event occurred by an unequal sister
      chromatid exchange that was mediated by LINE-1 repetitive elements.

PMID- 1356978
TI  - Glutamate 264 modulates the pH dependence of the NAD(+)-dependent D-lactate
      dehydrogenase.
AB  - Recently, we amplified the Lactobacillus bulgaricus NAD(+)-dependent D-lactate
      dehydrogenase gene by the polymerase chain reaction, cloned and overexpressed it
      in Escherichia coli (Kochhar, S., Chuard, N., and Hottinger, H. (1992) Biochem.
      Biophys. Res. Commun. 185, 705-712). Polymerase chain reaction-amplified DNA
      fragments may contain base changes resulting in mutant gene products. A
      comparison of specific activities of D-lactate dehydrogenase in the crude
      extracts of 50 recombinant clones indicated that one of the clones had
      drastically reduced enzyme activity. Nucleotide sequence analysis of the insert
      DNA showed an exchange of A to G at position 795 resulting in substitution of
      Glu264 to Gly in the D-lactate dehydrogenase. The purified mutant D-lactate
      dehydrogenase showed a shift of 2 units in its optimum pH toward the acidic
      range. The dependence of kcat/Km on the pH of the mutant enzyme showed that the
      pKa of the free enzyme was around 4, at least 2 pH units lower than that of the
      wild-type enzyme. Both the wild-type and the mutant enzyme at their respective
      optimum pH values showed similar kcat and Km values. The data suggest that the
      highly conserved Glu264 is not critical for enzyme catalysis, but it must be
      situated within hydrogen bonding distance to amino acid residue(s) involved in
      substrate binding as well as in catalysis.

PMID- 1356979
TI  - Functional involvement of P-glycoprotein in blood-brain barrier.
AB  - P-glycoprotein, an active efflux pump of antitumor agents in multidrug-resistant
      tumor cells, exists in various normal tissues, including brain capillaries. To
      study the physiological function of P-glycoprotein expressed in brain capillary
      endothelium, we established nine mouse brain capillary endothelial cell (MBEC)
      lines and examined the transport of antitumor agents across the monolayer of MBEC
      epithelia. In the MBECs, the activities of alkaline phosphatase and gamma
      glutamyl transpeptidase, specific markers for brain capillary endothelial cells,
      were about three times higher than those in other cells including human umbilical
      vein endothelial cells. By immunoblot analysis, P-glycoprotein was detected in
      all of the nine MBEC clones. The P-glycoprotein expressed in MBECs specifically
      bound [125I]iodoaryl azidoprazosin as that in multidrug-resistant cells, and
      efflux of vincristine was observed in the MBECs. When MBECs were grown on a
      porous filter membrane, they formed a monolayer of epithelium. By immunoelectron
      microscopic analysis, P-glycoprotein in MBEC epithelia was shown to be localized
      to the apical surface of the cells. Moreover, the unidirectional transepithelial
      transport of vincristine from basal side to apical side was demonstrated in
      vitro. These observations indicate that P-glycoprotein in brain capillary
      endothelium prevents vincristine from entering the central nervous system and
      thus may be one of the functional components of the blood-brain barrier.

PMID- 1356980
TI  - An extra cysteine proximal to the transmembrane domain induces differential cross
      linking of p185neu and p185neu.
AB  - The neu proto-oncogene encodes a receptor tyrosine kinase (p185) that is closely
      related to the epidermal growth factor receptor. It has been proposed that
      receptor tyrosine kinases are activated through oligomerization. Because this
      clustering model predicts that oligomerization of receptors is sufficient to
      activate them, we determined if p185 can be activated by introducing an extra
      cysteine proximal to the transmembrane domain. This should induce inter-receptor
      disulfide bonding and, according to the clustering model, activate the receptor.
      This amino acid substitution enhanced recovery of both normal and transforming
      neu proteins as dimers, with normal p185 recovered predominantly as monomers and
      transforming p185* as dimers. However, the cysteine substitution did not affect
      the transforming activity of the two proteins.

PMID- 1356981
TI  - Effects of hemin and porphyrin compounds on intersubunit disulfide formation of
      heme-regulated eIF-2 alpha kinase and the regulation of protein synthesis in
      reticulocyte lysates.
AB  - To study the mechanism by which heme regulates the heme-regulated eIF-2 alpha
      kinase (HRI), the effects of various protoporphyrin IX (PP) compounds on the
      kinase activities and intersubunit disulfide formation of HRI and on protein
      synthesis in reticulocyte lysates were examined. Hemin and cobalt protoporphyrin
      (CoPP) are more effective than ZnPP, NiPP, SnPP, and metal-free PP in promoting
      intersubunit disulfide bond formation in HRI, in inhibiting the autokinase and
      eIF-2 alpha kinase activities of HRI, in inhibiting phosphorylation of eIF-2
      alpha in rabbit reticulocytes, in maintaining protein synthesis, and in reversing
      the inhibition of protein synthesis in heme deficiency. There is an apparent
      correlation of in vitro intersubunit disulfide formation of HRI and the
      regulation of HRI kinase activities and protein synthesis by these porphyrin
      compounds. HRI in the reticulocyte lysate can be cross-linked by 1,6
      bismaleimidohexane (bis-NEM). The formation of bis-NEM cross-linked dimers in
      lysates is prevented completely by N-ethylmaleimide (NEM) which alkylates free
      sulfhydryl groups and is diminished by hemin and CoPP. These results support the
      view that HRI in hemin-supplemented lysates is in equilibrium between the
      noncovalently linked dimer and the disulfide-linked dimer. The molecular size of
      HRI in control, hemin-supplemented, or NEM-treated hemin-supplemented lysates is
      identical to that of purified HRI; activation of HRI and changes in its thiol
      status do not significantly affect its molecular size.

PMID- 1356982
TI  - Glucose stimulation of lipogenic enzyme gene expression in cultured white adipose
      tissue. A role for glucose 6-phosphate.
AB  - The expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) is
      low in the adipose tissue of suckling rats and increases markedly at weaning to a
      high carbohydrate diet. We have studied in vitro the factors regulating this
      phenomenon. Inguinal adipose tissue pieces from 19-day-old suckling rats were
      cultured for 6 or 24 h in minimal essential medium. Insulin (100 nM) added in the
      presence of lactate and pyruvate did not stimulate the expression of FAS and ACC.
      Glucose (20 mM) alone resulted in a 5-7-fold increase of FAS and ACC mRNA.
      Insulin potentiated the effect of glucose. 3-O-Methylglucose, a glucose analog
      that is transported into the cell but not metabolized, had no effect on FAS and
      ACC mRNA accumulation. However, 2-deoxyglucose (1 mM), a glucose analog which is
      phosphorylated to 2-deoxyglucose 6-phosphate, stimulated the expression of FAS
      and ACC to the same extent as 20 mM glucose. Glucose 6-phosphate concentrations
      in adipose tissue pieces cultured in various conditions changed in parallel with
      the FAS and ACC mRNA levels. We conclude that glucose 6-phosphate could be the
      metabolite involved in the stimulation of lipogenic enzyme gene expression in
      response to glucose.

PMID- 1356983
TI  - IMP dehydrogenase inhibitors reduce intracellular tetrahydrobiopterin levels
      through reduction of intracellular GTP levels. Indications of the regulation of
      GTP cyclohydrolase I activity by restriction of GTP availability in the cells.
AB  - GTP cyclohydrolase I exhibits a positive homotropic cooperative binding to GTP,
      which raises the possibility of a role for GTP in regulating the enzyme reaction
      (Hatakeyama, K., Harada, T., Suzuki, S., Watanabe, Y., and Kagamiyama, H. (1989)
      J. Biol. Chem. 264, 21660-21664). We examined whether or not the intracellular
      GTP level is within the range of affecting GTP cyclohydrolase I activity, using
      PC-12 rat pheochromocytoma and IMR-32 human neuroblastoma cells. Since GTP
      cyclohydrolase I was the rate-limiting enzyme for the biosynthesis of
      tetrahydrobiopterin in these cell lines, the intracellular activities of this
      enzyme were reflected in the tetrahydrobiopterin contents. We found that the
      addition of guanine or guanosine increased GTP but not tetrahydrobiopterin in
      these cells. On the other hand, three IMP dehydrogenase inhibitors, tiazofurin, 2
      amino-1,3,4-thiadiazole, and mycophenolic acid, decreased both GTP and
      tetrahydrobiopterin in a parallel and dose-dependent manner, and these effects
      were reversed by the simultaneous addition of guanine or guanosine. There was no
      evidence suggesting that these inhibitors inhibited other enzymes involved in the
      biosynthesis and regeneration of tetrahydrobiopterin. Comparing intracellular
      activities of GTP cyclohydrolase I in the inhibitor-treated cells with its
      substrate-velocity curve, we estimated that the intracellular concentration of
      free GTP is 150 microM at which point the activity of GTP cyclohydrolase I is
      elicited at its maximum velocity. Below this GTP concentration, GTP
      cyclohydrolase I activity is rapidly decreased. Therefore GTP can be a regulator
      for tetrahydrobiopterin biosynthesis.

PMID- 1356984
TI  - Molecular basis for the interaction of histamine with the histamine H2 receptor.
AB  - We undertook these studies to characterize the molecular basis of the interaction
      of histamine with the H2 receptor. Key areas of homology in the structures of the
      histamine H2 and beta 2 adrenergic receptor suggested specific transmembrane
      amino acids that might be important for binding of histamine. A third
      transmembrane aspartic acid of the histamine receptor (Asp98), thought to serve
      as a counter anion that interacts with the cationic amine moiety of histamine,
      was mutated to Asn98, and the mutated receptor was expressed in Hepa cells.
      Removal of the negatively charged amino acid abolished both binding of the H2
      receptor antagonist [methyl-3H]tiotidine and histamine stimulated increases in
      cellular cAMP content. Mutation of a fifth transmembrane aspartic acid (Asp186)
      to Ala186 or Asn186 by itself or in conjunction with mutation of another fifth
      transmembrane amino acid (Thr190 to Ala190) resulted in a loss of [methyl-3H]
      tiotidine binding, although the generation of cAMP in response to histamine was
      maintained. The histamine receptor with only a Thr190 to Ala190 or Cys190
      mutation retained the ability to bind [methyl-3H]tiotidine, but both the affinity
      and efficacy of binding were reduced. These data lead us to propose a model for
      histamine binding in which Asp98 is essential for histamine binding and action,
      Asp186 defines H2 selectivity, and Thr190 is important in establishing the
      kinetics of histamine binding, but is not essential for H2 selectivity.

PMID- 1356985
TI  - GroE dependence of refolding and holoenzyme formation of 6-hydroxy-D-nicotine
      oxidase.
AB  - In Escherichia coli cells expressing 6-hydroxy-D-nicotine oxidase (6-HDNO), a
      flavoprotein with covalently bound FAD, approximately 40% of the polypeptide is
      in its apoform. We investigated whether in vivo holoenzyme formation was
      influenced by the association of the apoenzyme with cellular chaperones.
      Immunoprecipitation of apoenzyme-containing cell extract with protein-A-Sepharose
      bound 6-HDNO- or GroEL-specific antibodies failed to reveal the formation of
      complexes between these proteins. The limiting factor in holoenzyme formation in
      vivo appeared to be the intracellular supply of phosphorylated tricarbon
      compounds (e.g. glycerol-3-P) acting as allosteric effectors in the flavinylation
      reaction. When holoenzyme formation from purified apo6-HDNO was investigated in
      vitro, addition of GroEL and GroES to the reaction assays increased the yield of
      holoenzyme formation. The observed increase in apoenzyme to holoenzyme transition
      was ATP independent, and the effect of GroE could be simulated by high
      concentrations of glycerol (40%). Apparently, a nonspecific protein-protein
      interaction between the GroE proteins and the apo6-HDNO favored holoenzyme
      formation. The refolding of guanidinium hydrochloride-unfolded holoenzyme,
      however, was catalyzed by GroEL and GroES in an ATP-dependent reaction. Recovery
      of the native, enzymatically active, conformation ranged from 30 to 40%. When
      apo6-HDNO was denatured and refolded, the same dependence on GroE and ATP was
      observed in the recovery of a conformation able to incorporate FAD and to
      holoenzyme. [14C] FAD in the refolding assay yielded radioactively labeled 6-HDNO
      demonstrating the autocatalytical covalent incorporation of FAD into the
      polypeptide during the folding process.

PMID- 1356986
TI  - Characterization of the azidopine and vinblastine binding site of P-glycoprotein.
AB  - To determine the number of drug binding sites that exist on the multidrug
      transporter, P-glycoprotein, we used azidopine, a dihydropyridine photoaffinity
      compound that reverses multidrug resistance and labels P-glycoprotein. Azidopine
      labels P-glycoprotein in two distinct locations: one labeled site is within the
      amino half of P-glycoprotein between amino acid residues 198 and 440, and the
      other site is within the carboxy half of the protein. Vinblastine is a cytotoxic
      drug that is used in cancer chemotherapy and is a substrate for transport by P
      glycoprotein. We found that vinblastine inhibits azidopine labeling to
      approximately the same extent at each labeled site on P-glycoprotein. Because
      several studies have shown that amino acid residue 185 of P-glycoprotein plays a
      critical role in some aspects of drug binding and transport, we also studied the
      effect that amino acid residue 185 has on azidopine labeling. These studies show
      that azidopine labels both sites equivalently in both wild-type (G185) and mutant
      (V185) P-glycoproteins. We conclude from our results that the two halves of P
      glycoprotein approach each other to form a single binding site for these drugs.

PMID- 1356987
TI  - Characterization of dynorphin A-converting enzyme in human spinal cord. An
      endoprotease related to a distinct conversion pathway for the opioid
      heptadecapeptide?
AB  - A highly specific proteinase, converting dynorphin A (1-17) to enkephalins, was
      isolated from the human spinal cord and subjected to further characterization.
      The enzyme was found to be a thiol-dependent protein with a relative molecular
      mass of 50 kDa and a pH optimum between 5.0 and 5.5. This proteinase appears to
      exclusively convert dynorphin A (1-17) to Leu-enkephalin and its COOH-terminal
      extensions Leu-enkephalin-Arg6 (which was a major conversion product) and Leu
      enkephalin-Arg6-Arg7 but not the other prodynorphin- or proenkephalin-derived
      peptides. This high specificity toward a single structure is suggested to be
      involved in a distinct processing pathway associated with the generation of the
      opioid peptides with selectivity for delta-opioid receptors.

PMID- 1356988
TI  - Tetanus toxin and botulinum toxins type A and B inhibit glutamate, gamma
      aminobutyric acid, aspartate, and met-enkephalin release from synaptosomes. Clues
      to the locus of action.
AB  - Tetanus toxin (100 nM) when preincubated with guinea pig cerebrocortical
      synaptosomes for 45 min reduces the final extent of the KCl-evoked, Ca(2+)
      dependent, glutamate transmitter release to 30% of non-intoxicated controls.
      Similarly, 100 nM Botulinum neurotoxins, types A and B, preincubated for 90 min
      inhibit release to 45-60% of non-intoxicated controls. The toxins preferentially
      attenuate a slow phase of KCl-evoked glutamate release which may be associated
      with synaptic vesicle mobilization. Tetanus toxin additionally inhibits the
      release of aspartate, gamma-aminobutyric acid and met-enkephalin from the same
      preparation. Since amino acids and neuropeptides are released by distinct
      mechanisms, this indicates that the toxin affects a step common to both
      exocytotic pathways. When Ba2+ (which does not interact with calmodulin) is
      substituted for Ca2+, the control KCl-evoked release of each transmitter is
      unaffected and tetanus toxin is still inhibitory. Taken together these results
      implicate a calmodulin-independent locus (or loci) of action common to small- and
      large-dense-core vesicles and associated with vesicle transport.

PMID- 1356989
TI  - Biosynthesis and degradation of altered immature forms of intestinal dipeptidyl
      peptidase IV in a rat strain lacking the enzyme.
AB  - We have used a strain of rat (Fischer 344) lacking brush border membrane
      dipeptidyl peptidase IV activity to examine its effect on the intestinal
      assimilation of prolyl peptides. In addition, we have examined the biochemical
      basis for the enzyme deficiency. An analysis of several brush border membrane
      hydrolases in different regions of the small intestine demonstrates that these
      rats lack only dipeptidyl peptidase IV. They also have a greatly reduced ability
      to hydrolyze and absorb in vivo peptides of the NH2-X-Pro-Y type which are known
      substrates for the enzyme. Immunoblot analysis with polyclonal and monoclonal
      antibody indicates that the animals lack an identifiable dipeptidyl peptidase IV
      protein in intestinal epithelial cells. Levels and types of dipeptidyl peptidase
      IV mRNA were analyzed in several tissues and found to be similar to that of
      control animals. Biosynthetic labeling of intestinal explants revealed that two
      distinct forms (102 and 108 kDa) of dipeptidyl peptidase IV are initially
      synthesized by deficient rats, in contrast to the single protein (106 kDa)
      observed in normal animals. Pulse-chase labeling experiments (+/- endoglycosidase
      H) show that these two altered forms of dipeptidyl peptidase IV, although
      initially glycosylated with N-linked high mannose carbohydrate, fail to be
      processed to the mature complex glycosylated form and undergo intracellular
      degradation.

PMID- 1356990
TI  - Mechanism of action of a cellular inhibitor of the dsRNA-dependent protein kinase
      from 3T3-F442A cells.
AB  - When mouse 3T3-F442A preadipocyte fibroblasts reach confluence in the appropriate
      culture medium, their growth is arrested, and the cells undergo terminal
      differentiation to adipocytes. Two proteins that may be involved in this process
      are interferon and the interferon-induced double-stranded RNA (dsRNA)-dependent
      protein kinase (DAI). In 3T3-F442A cells, interferon and DAI are transiently
      expressed with a maximum level of active kinase appearing at confluence.
      Interestingly, the level of active DAI was found to be low when cells were
      maintained under conditions nonpermissive for differentiation. This reduction in
      DAI was at least partly because of the presence of elevated levels of a specific
      inhibitor of DAI, termed dRF, which appeared to be a reversible inhibitor of the
      autophosphorylation (activation) of DAI. In the present study, the mechanism of
      action of dRF was investigated. Photocross-linking experiments indicated that dRF
      prevented the binding of ATP to DAI. Since the binding of ATP to DAI is dsRNA
      dependent, we examined the effect of dRF on the binding of dsRNA to the kinase
      using RNA mobility shift assays. dRF was found to prevent the formation of DAI
      dsRNA complexes without a direct effect on the dsRNA. This suggests that dRF
      exerts its effect through an interaction with DAI.

PMID- 1356991
TI  - Human natriuretic peptide receptor-A guanylyl cyclase. Hormone cross-linking and
      antibody reactivity distinguish receptor glycoforms.
AB  - Most of the physiological actions of atrial natriuretic peptide (ANP) may be
      attributed to activation of the natriuretic peptide receptor-A (NPR-A) guanylyl
      cyclase. We report here that truncation of the NPR-A cytoplasmic domain results
      in increased expression of cell surface ANP binding sites. The truncated receptor
      exhibited a hyperbolic time course for ANP binding and had a high affinity for
      [125I]hANP, Kd = 8 pM. Cells expressing truncated NPR-A were used as an immunogen
      to obtain monoclonal antibodies against the native conformation of the
      extracellular domain. These antibodies were used to select for high levels of
      stable NPR-A expression in 293 cells, by fluorescence-activated cell sorting.
      Disuccinimidyl suberate cross-linked [125I]ANP to 135-kDa NPR-A on intact cells.
      Monoclonal antibody immunoprecipitation of 35S-labeled proteins revealed NPR-A
      size heterogeneity, with 135- and 125-kDa species. A synthetic peptide antibody
      directed against the extracellular domain immunoprecipitated 125-kDa NPR-A, but
      recognized both sizes of receptor by Western blotting. The 125-kDa NPR-A did not
      bind to or cross-link ANP. NPR-A size variants were expressed on the cell
      surface, and heterogeneity was removed by deglycosylation with protein:N
      glycosidase F. Our results suggest that the degree of N-linked glycosylation of
      the NPR-A extracellular domain influences the ability to bind ANP.

PMID- 1356993
TI  - Complications of replantation surgery.
AB  - Potential complications after replantation surgery are numerous and varied in
      their nature. The average replantation patient can expect somewhere between two
      to three subsequent operations to maximize function. Many surgical complications
      and unsatisfactory functional outcomes can be avoided through careful assessment
      of patients and their injuries.

PMID- 1356992
TI  - Expression of tissue transglutaminase in Balb-C 3T3 fibroblasts: effects on
      cellular morphology and adhesion.
AB  - Tissue transglutaminase is a cytosolic enzyme whose primary function is to
      catalyze the covalent cross-linking of proteins. To investigate the functions of
      this enzyme in physiological systems, we have established lines of Balb-C 3T3
      fibroblasts stably transfected with a constitutive tissue transglutaminase
      expression plasmid. Several cell lines expressing high levels of catalytically
      active tissue transglutaminase have been isolated and characterized.
      Transglutaminase-transfected cells showed morphologic features quite distinct
      from their nontransfected counterparts. Many of the cells showed an extended and
      very flattened morphology that reflected increased adhesion of the cells to the
      substratum. Other cells, particularly those showing the highest levels of
      intracellular transglutaminase expression, showed extensive membrane blebbing and
      cellular fragmentation. The results of these experiments suggest that the
      induction and activation of tissue transglutaminase may contribute both to
      changes in cellular morphology and adhesiveness.

PMID- 1356995
TI  - Hippocampal CA3 lesion prevents postconcussive metabolic dysfunction in CA1.
AB  - Immediately following fluid-percussion (F-P) brain injury, the hippocampus
      exhibits a marked increase in its local CMRglc (LCMRglc; mumol/100 g/min) as
      determined using [14C]2-deoxy-D-glucose autoradiography. This injury-induced
      increase in metabolism is followed in 6 h by a subsequent decrease in LCMRglc.
      These two postinjury metabolic states may be the result of ionic disruptions
      following trauma via stimulation of glutamate-gated ion channels. To determine if
      endogenous glutamate innervation to the CA1 region of the hippocampus can provide
      an anatomical basis for this proposed mechanism, it was removed by kainic-acid
      induced destruction of CA3, and the effect on CA1 metabolism following concussive
      injury was studied. Five days before a lateral F-P injury (3.5-4.5 atm), kainic
      acid (0.5 microgram) or vehicle was stereotaxically injected into the left
      ventricle of 65 rats. Histological inspection indicated that kainic acid produced
      severe cell loss primarily in the CA3 region of the hippocampus ipsilateral to
      the injection. The metabolic results indicated that immediately following injury,
      animals with an intact hippocampus exhibited an increase in LCMRglc to 84.6 +/- 5
      within the CA1 region, representing a 81.5% increase over controls. However, in
      the CA3-lesioned animals, CA1 showed no evidence of an injury-induced
      hypermetabolism, with LCMRglc remaining at control levels (51.4 +/- 3.9). At 6 h
      postinjury, the intact hippocampus exhibited a reduction of LCMRglc to rates of
      40.7 +/- 4.7 within the CA1 region, representing a 17.9% reduction compared with
      controls. In contrast, CA3-lesioned animals exhibited less of an injury-induced
      decrease in LCMRglc within the CA1 region, exhibiting a mean rate of 43.4 +/-
      4.5, representing only a 12.5% reduction compared with controls. These results
      indicate that the removal of the CA3 projection to CA1 protects the CA1 cells
      from the metabolic dysfunction typically seen following injury. This supports our
      previous work indicating the important role glutamate plays in the ionic flux and
      subsequent metabolic changes that follow traumatic brain injury.

PMID- 1356994
TI  - Effect of dichloroacetate on recovery of brain lactate, phosphorus energy
      metabolites, and glutamate during reperfusion after complete cerebral ischemia in
      rats.
AB  - The effects of dichloroacetate (DCA) on brain lactate, intracellular pH (pHi),
      phosphocreatine (PCr), and ATP during 60 min of complete cerebral ischemia and 2
      h of reperfusion were investigated in rats by in vivo 1H and 31P magnetic
      resonance spectroscopy; brain lactate, water content, cations, and amino acids
      were measured in vitro after reperfusion. DCA, 100 mg/kg, or saline was infused
      before or immediately after the ischemic period. Preischemic treatment with DCA
      did not affect brain lactate or pHi during ischemia, but reduced lactate and
      increased pHi after 30 min of reperfusion (p < 0.05 vs. controls) and facilitated
      the recovery of PCr and ATP during reperfusion. Postischemic DCA treatment also
      reduced brain lactate and increased pHi during reperfusion compared with controls
      (p < 0.05), but had little effect on PCr, ATP, or Pi during reperfusion. After 30
      min of reperfusion, serum lactate was 67% lower in the postischemic DCA group
      than in controls (p < 0.05). The brain lactate level in vitro was 46% lower in
      the postischemic DCA group than in controls (p < 0.05). DCA did not affect water
      content or cation concentrations in either group, but it increased brain
      glutamate by 40% in the preischemic treatment group (p < 0.05). The potential
      therapeutic effects of DCA on brain injury after complete ischemia may be
      mediated by reduced excitotoxin release related to decreased lactic acidosis
      during reperfusion.

PMID- 1356996
TI  - Basic mechanisms of pain.
AB  - It has been well established that pain reflects complex, linked neuroendocrine
      responses that go far beyond a sensory alarm system. Accordingly, there may be
      significant medical consequences of inadequate recognition or treatment of pain.

PMID- 1356997
TI  - White matter dysfunction and its neuropsychological correlates: a longitudinal
      study of a case of metachromatic leukodystrophy treated with bone marrow
      transplant.
AB  - A 10-year-old white female who had received a bone marrow transplant (BMT) at 57
      months of age as treatment for late infantile onset metachromatic leukodystrophy
      (MLD), a neurodegenerative autosomal recessive storage disease, showed
      stabilization of the cognitive degenerative process and demonstrated a partial
      pattern of cognitive deficits and behavioral abnormalities that has been called
      NLD (nonverbal learning disabilities) associated with white matter disease. A
      pattern of good rote memory, reading skills, and concrete language contrasted
      with poor visual spatial skills, mathematics, and abstract problem solving. She
      did not show the usual speech prosody and social deficits associated with NLD.

PMID- 1356998
TI  - Human and tick spotted fever group Rickettsia isolates from Israel: a genotypic
      analysis.
AB  - The genomes of spotted fever group rickettsiae isolated in different geographical
      areas of Israel (two from ticks and four from humans, obtained over a span of 20
      years) were studied by polymerase chain reaction (PCR) and restriction
      endonuclease fragment length polymorphism (RFLP) analysis. The human isolates
      were obtained from patients suffering from rickettsial disease of different
      degrees of severity. The PCR products obtained with five pairs of oligonucleotide
      primers (two primer sets derived from the 190-kDa polypeptide gene and three from
      the 120-kDa polypeptide gene) and cleaved with restriction endonucleases were
      used to study the Israeli isolates and reference Rickettsia conorii isolates.
      Subtle differences between the PCR-RFLP patterns of Israeli isolates and the two
      R. conorii reference strains (Moroccan and no. 7) were seen when the PCR products
      derived from the 190-kDa gene-derived primer sets were digested. All of the
      Israeli isolates were identical by RFLP analysis using all of the primer sets.
      This study showed that the Israeli spotted fever group isolates (from both ticks
      and humans) were genetically homogeneous by the criteria used in this study,
      despite the time and location differences in their original isolation, and
      different as a group from R. conorii.

PMID- 1356999
TI  - Comparison of molecular typing methods for Candida albicans.
AB  - Four molecular approaches to determining the types of Candida albicans strains
      were compared. The strains used were those whose repeated DNA (ribosomal and
      mitochondrial) EcoRI restriction fragment length polymorphisms (RFLP) were
      determined by Stevens et al. (D. A. Stevens, F. C. Odds, and S. Scherer, Rev.
      Infect. Dis. 12:258-266, 1990). Scherer and Stevens (S. Scherer and D. A.
      Stevens, Proc. Natl. Acad. Sci. USA 85:1452-1456, 1988) used the same strains to
      examine the Southern blots of genomic EcoRI digests probed with the repeated
      sequence 27A. The results of these investigators were compared with
      determinations of RFLPs generated from repeated DNA by the enzyme HinfI and
      examination of the karyotypes of strains under two sets of conditions, one for
      the smaller chromosomes and one for the larger ones. Analysis of RFLPs of
      repeated DNA is most convenient but shows the lowest degree of resolution. Use of
      the repeated sequence and use of karyotype have very high resolution, but the
      former method is more convenient than the latter. HinfI digestion is more
      sensitive than EcoRI digestion but equally convenient. By using all four methods,
      separate types were identified for 18 of the 20 strains examined.

PMID- 1357000
TI  - Restriction fragment length polymorphism analysis of 16S ribosomal DNA of
      Streptococcus and Enterococcus species of bovine origin.
AB  - Twelve bacterial species including Streptococcus uberis, S. parauberis, S.
      agalactiae, S. dysgalactiae, S. bovis, S. mitis, S. salivarius, S.
      saccharolyticus, Enterococcus faecium, E. faecalis, E. avium, and Aerococcus
      viridans were examined for their 16S ribosomal DNA fingerprint patterns.
      Oligonucleotide primers complementary to 16S rRNA genes were used to amplify by
      the polymerase chain reaction 16S ribosomal gene fragments from genomic DNAs. The
      molecular sizes of the amplified 16S ribosomal DNA (rDNA) fragments from the 12
      species examined ranged from 1,400 to 1,500 bp. Restriction fragment length
      polymorphism analysis of 16S rDNA was performed with 11 different restriction
      endonucleases. All 12 species examined could be differentiated on the basis of
      characteristic 16S rDNA fingerprint patterns by using the restriction
      endonucleases HhaI, RsaI, and MspI. A scheme for the differentiation of the 12
      species is presented. Eleven isolates representing 11 species were obtained from
      cows with intramammary infections and were examined by 16S rDNA fingerprinting.
      All 11 species isolated from cows were differentiated by using HhaI, RsaI, and
      MspI restriction endonucleases. The results of this study demonstrate the
      potential application of 16S rDNA fingerprinting for the identification and
      differentiation of bacterial species.

PMID- 1357001
TI  - Usefulness of the ID32 staph system and a method based on rRNA gene restriction
      site polymorphism analysis for species and subspecies identification of
      staphylococcal clinical isolates.
AB  - The usefulness of the ID32 Staph System and a method based on rRNA gene
      restriction site polymorphism was evaluated by the study of 42 staphylococcal
      clinical isolates phenotypically difficult to identify. The ID32 Staph
      micromethod and the genomic method are adapted for recognition of 27 and 31
      staphylococcal taxa, respectively. The genomic method is based on a Dice analysis
      of the hybridization patterns obtained by cutting the cellular DNA either with
      EcoRI or with HindIII and by probing with pBA2, containing the Bacillus subtilis
      gene encoding 16S rRNA, labeled either with [alpha-32P]dCTP or with
      acetylaminofluorene. This study showed that the nonradioactive labeling provided
      a better resolution of the hybridizing bands than radioactive labeling. Of the 42
      isolates selected, only 22 could be assigned to a staphylococcal species by the
      ID32 Staph System, whereas 35 could be identified by the genomic method. This
      latter method also enabled the screening of three unclassified isolates having
      hybridization patterns more closely related to each other than to any of the 31
      staphylococcal taxa investigated. These three isolates could belong to a
      staphylococcal taxon not yet described.

PMID- 1357002
TI  - Modulation of airway inflammation in cystic fibrosis. In vivo suppression of
      interleukin-8 levels on the respiratory epithelial surface by aerosolization of
      recombinant secretory leukoprotease inhibitor.
AB  - Based on the knowledge that neutrophil elastase (NE) in cystic fibrosis (CF)
      epithelial lining fluid (ELF) can induce human bronchial epithelial cells to
      express the gene for interleukin 8 (IL-8), an 8.5-kD neutrophil chemoattractant,
      we have evaluated CF ELF for the presence of IL-8, and investigated the ability
      of aerosolized recombinant secretory leukoprotease inhibitor (rSLPI) to suppress
      NE, and hence IL-8, levels on the respiratory epithelial surface in CF. Enzyme
      linked immunoassay revealed 21.9 +/- 4.8 nM IL-8 in CF ELF compared with none in
      normals. Active NE was detectable in ELF of all individuals with CF and was
      significantly decreased (P < 0.03) after aerosolization of rSLPI. Human bronchial
      epithelial cells exposed to CF ELF recovered before rSLPI therapy expressed IL-8
      mRNA transcripts, but ELF recovered after rSLPI therapy induced far less
      bronchial epithelial cell IL-8 gene expression. Consistent with this, rSLPI
      aerosol therapy caused a marked reduction in CF ELF IL-8 levels (P < 0.05) and
      neutrophil number (P < 0.02). There was also a clear association between CF ELF
      active NE and IL-8 levels (r = 0.94). These data suggest that rSLPI therapy not
      only suppresses respiratory epithelial NE levels, but also breaks a cycle of
      inflammation on the CF epithelial surface.

PMID- 1357004
TI  - Tumour markers and radiological examinations in the follow-up of patients with
      oral cancer.
AB  - In 1986, a new follow-up programme for patients with oral cancer was introduced
      in our department. The follow-up programme included liver function tests, tumour
      markers and radiological examination. 63 patients were monitored to the end of
      1990. The results showed that serum Carcinoembryonic Antigen (CEA) assays were
      not sensitive enough to detect early cancer, recurrences or metastases. Neither
      was there any difference between the preoperative CEA levels of patients with and
      without recurrence during follow-up. The levels of salivary CEA, were similar to
      those of healthy individuals. Serum CA 19-9 values were consistently normal. In 1
      patient, the first sign of liver metastases was a high 5-nucleotidase level. No
      recurrences were detected by radiological examination. In conclusion, the
      importance of frequent and careful clinical observation is emphasized; all 20
      recurrences at the primary site and in local lymphnodes were detected by clinical
      examination. For detection of oral cancer recurrences, several laboratory and
      radiological examinations seem unnecessary. The cost-benefit of those
      examinations is significantly low.

PMID- 1357003
TI  - Neutrophil induced oxidative injury of cardiac myocytes. A compartmented system
      requiring CD11b/CD18-ICAM-1 adherence.
AB  - We have previously shown that cytokines and postischemic cardiac lymph induce
      expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on canine adult
      cardiac myocytes. ICAM-1 expression allows adherence of activated neutrophils to
      myocytes that is blocked by anti-CD18 mAb, R15.7, or anti-ICAM-1 mAb, CL18/6.
      Interleukin 1, tumor necrosis factor-alpha, or interleukin 6-stimulated cardiac
      myocytes were loaded with 2',7'-dichlorofluorescin, and oxidation to the
      fluorescent dichlorofluorescein was monitored. Fluorescence and
      neutrophil/myocyte adherence followed the same time course, and both were blocked
      by monoclonal antibodies to CD18, CD11b, and ICAM-1, but mAb R7.1, recognizing a
      functional epitope on CD11a, was not inhibitory. The iron chelator,
      desferroxamine, and the hydroxyl radical scavenger, dimethylthiourea, did not
      inhibit neutrophil adherence, but completely inhibited fluorescence. In contrast,
      the extracellular oxygen radical scavengers superoxide dismutase and catalase,
      and the extracellular iron chelator, starch-immobilized desferroxamine, did not
      affect either fluorescence or adherence. Under the experimental conditions used,
      no superoxide production could be detected in the extracellular medium.
      Fluorescence microscopy demonstrated that fluorescence began within 5 min after
      neutrophil adherence to an individual myocyte, and myocyte contracture followed
      rapidly. Fluorescent intensity was highest initially at the site of myocyte
      neutrophil adherence. When only neutrophils were loaded with 2',7'
      dichlorofluorescein, fluorescence was observed only in those neutrophils adhering
      to the cardiac myocytes. Thus, adherence dependent on Mac-1 (CD11b/CD18) and ICAM
      1 (CD54) activates the neutrophil respiratory burst resulting in a highly
      compartmented iron-dependent myocyte oxidative injury.

PMID- 1357005
TI  - Proliferating cell nuclear antigen and S phase fraction in endometrial stromal
      sarcoma.
AB  - AIMS: To investigate the value of immunohistochemical staining for the cell cycle
      protein proliferating cell nuclear antigen (PCNA) and flow cytometric S phase
      fraction in determining prognosis in endometrial stromal sarcoma, graded
      according to mitotic count. METHODS: Seventeen endometrial stromal sarcomas from
      13 patients treated at the Royal Marsden Hospital were analysed. Serial 5 microns
      sections were cut for haematoxylin and eosin and immunohistochemical staining for
      PCNA, performed using the murine monoclonal antibody PC10. PCNA positivity was
      expressed as a percentage of the total number of cells (PCNA index). Flow
      cytometric analysis was performed on nuclei extracted from paraffin wax sections.
      RESULTS: In the five patients who died of disease within five years, PCNA index
      varied between < 1% and 60% (mean 21%) and S phase fraction ranged from 11.3 and
      20.1 (mean 13.8). Four patients who were apparently cured showed PCNA indices
      ranging from < 1% to 5% (mean 1.75%) and S phase fraction ranging from 1.4 to 3.5
      (mean 2.3); and three patients alive with disease showed PCNA indices ranging
      from 1% to 15% (mean 8.6%) and S phase fraction ranging from 1.4 to 3.5 (mean
      2.3). One patient who died from indolent local disease after nine years showed a
      PCNA of 1 or less and an S phase fraction of 0.9. CONCLUSIONS: PCNA staining was
      variable and therefore not a reliable prognostic indicator, but a high PCNA index
      was only found in those patients dying of disease within five years. A stronger
      association was seen between S phase fraction and prognosis; this also correlated
      well with histological grade determined by mitotic count. In individual
      borderline cases that are between low and high grade categories, these procedures
      may be useful.

PMID- 1357006
TI  - HER2 (c-erbB-2) oncoprotein expression in colorectal adenocarcinoma: an
      immunohistological study using three different antibodies.
AB  - Paraffin wax sections of 70 surgically resected colorectal adenocarcinomas were
      examined for the overexpression of HER2/c-erbB-2 oncoprotein using three
      different specific antibodies and the avidin-biotin immunoperoxidase technique.
      The patients included 38 men and 32 women aged between 47 and 80 years. The
      tumours were derived from various parts of the large intestinal tract, and
      represented all three stages of Dukes' classification and the three histological
      grades of differentiation. Many tumour sections also included adjacent normal or
      transitional mucosa. Eight tubular adenomas found in the colectomy specimens in
      association with some carcinomas were also examined. No positive membrane
      staining was seen in any of the 70 carcinomas, four adenomas, two hyperplastic
      polyps, nor in the adjacent normal or transitional mucosa. It is suggested that
      the overexpression of c-erbB-2 gene product is unlikely to be as common and as
      pronounced in colorectal adenocarcinoma as it is in ductal carcinoma of the
      breast.

PMID- 1357007
TI  - Glutamate-immunoreactive terminals synapse on primate spinothalamic tract cells.
AB  - Glutamate has been shown to excite spinothalamic tract (STT) neurons and has been
      localized to primary afferent neurons, spinal cord projection neurons, and
      interneurons in the spinal cord dorsal horn. The likelihood that glutamate
      immunoreactive (GLU-IR) terminals directly innervate STT neurons was
      investigated. For these studies three lamina IV or V STT cells in the lumbar
      spinal cords of three monkeys (Macaca fascicularis) were identified
      electrophysiologically and characterized. Two were identified as high threshold
      neurons and one as a wide dynamic range neuron. Following intracellular injection
      of the cells with HRP and reaction to give the cells a Golgi-like appearance, the
      tissues were processed for electron microscopy. Postembedding immunogold methods
      with antibodies specific for glutamate were used to identify GLU-IR terminals
      apposing the somata and dendrites of the STT neurons, including dendrites that
      extended into laminae IV and III. The GLU-IR terminals were numerous and
      constituted a mean of 46% of the population counted that appose the STT soma and
      50% of the profiles apposing the dendrites. Fifty-four percent of the somatic and
      50% of the dendritic surface length was contacted by GLU-IR terminals. Most
      terminals contained round clear vesicles and some contained a variable number of
      large dense core vesicles. For one of the three cells examined it was determined
      that 45% of the terminals apposing the soma were GLU-IR and 30% of the terminals
      were gamma aminobutyric acid-immunoreactive (GABA-IR). In an additional monkey, a
      lamina I cell retrogradely labeled from the ventral posterolateral nucleus of the
      thalamus was found to be ensheathed in glial processes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1357009
TI  - Expression of cholecystokinin and somatostatin genes in the human thalamus.
AB  - The cholecystokinin (CCK) gene is expressed in thalamocortical and thalamo
      striatal neurons of the rat. In the cat, this peptide is found in some
      intralaminar and midline nuclei, whereas somatostatin (SRIF) is expressed in the
      reticular nucleus of the cat but not in rat. Since the putative neurotransmitters
      used by thalamic neurons are still incompletely known, especially in humans, we
      investigated the expression of the CCK and SRIF genes in the human thalamus by
      using hybridization histochemistry. CCK mRNA was found in many neurons, located
      in several nuclei of the dorsal thalamus. They were especially numerous and
      widespread in the nuclei associated with the internal thalamic lamina. They
      formed a continuum in the basal medial thalamus, from the central-medial nucleus,
      through the centre median/parafascicular complex to the limitans and
      suprageniculate nuclei. In addition, neurons with CCK mRNA were found medially
      and laterally to the mediodorsal nucleus, in the midline and intralaminar nuclei.
      Only rare neurons with CCK mRNA were found in other nuclei (e.g., in the ventral
      group of nuclei). SRIF mRNA was found in many neurons of the reticular nucleus,
      but not in the dorsal thalamus. Neurochemical features of the human thalamus, for
      the genes studied here, resemble those found in the cat. SRIF may play a role in
      modulating dorsal thalamic impulses, which may be conveyed through CCK
      innervation to the striatum and, partly, to the cortex.

PMID- 1357008
TI  - Sex differences in densities of dopaminergic fibers and GABAergic neurons in the
      prenatal rat striatum.
AB  - On the basis of observations on dopaminergic neurons developing in gender
      specific cultures of embryonic rat mesencephalon, we have hypothesized that as
      yet unknown sexual dimorphisms might be found in projection areas of dopaminergic
      neurons. Therefore we searched for possible sex differences in the striatum
      during the period when massive ingrowth of mesencephalic afferents occurs and the
      striatal gamma-aminobutyric acid (GABA)ergic neurons differentiate. Male and
      female rats of embryonic days (E) 16, 18, 20, and 21 were fixed by perfusion
      through the heart. Vibratome sections were cut from the striatal anlage and
      sequentially immunostained for GABA by the immunogold-silver technique and
      tyrosine hydroxylase (TH) by the avidin-biotin-peroxidase method. Ultrathin
      sections were scanned for numbers of GABA- and TH-immunoreactive (IR) elements.
      Densities of TH-IR axons as well as of GABA-IR cell body profiles progressed with
      time. Contacts between TH-IR axons and GABA-IR and immunonegative cells were
      observed as early as E-16, increasing in numbers toward later stages. Throughout
      prenatal development, female striata displayed higher densities of both TH-IR
      axon and GABA-IR cell body profiles than male ones. This is the first report of a
      distinct anatomical sex difference regarding two major components of a key center
      of motor control. Prenatal sexual differentiation of the striatum may lead to a
      sexually dimorphic extrapyramidal circuitry, the existence of which, in the
      adult, is suggested by experimental and clinical data.

PMID- 1357010
TI  - Molluscum contagiosum in patients with human immunodeficiency virus infection. A
      review of twenty-seven patients.
AB  - BACKGROUND: Molluscum contagiosum (MC) is a common and at times severely
      disfiguring cutaneous viral infection in patients with human immunodeficiency
      virus (HIV) infection. OBJECTIVE: The purpose of this study was to describe the
      clinical course of MC in patients with HIV infection and to examine the relation
      between presentation of MC and the stage of HIV infection, as measured by T-cell
      subsets. METHODS: This is a retrospective case study of 27 patients with MC and
      HIV infection who had T-cell subset determination within 60 days of diagnosis of
      MC. RESULTS: The overall mean CD4+ count, CD4+ percentage, and CD4+/CD8+ ratio
      were 85.7/mm3, 5.9%, and 0.10, respectively. An inverse relation between CD4+
      count and the number of MC lesions was observed (p = 0.0023). Fourteen patients
      (52%) had facial and neck lesions alone, and seven (26%) had lesions in areas
      associated with sexual transmission. Pneumocystis carinii pneumonia had occurred
      in 8 patients (31%) and Kaposi's sarcoma in 15 patients (56%). CONCLUSION: MC can
      occur as a late manifestation of HIV infection and is a cutaneous correlate of
      cellular immune deficiency.

PMID- 1357011
TI  - Intraepidermal localization of the clone in cutaneous T-cell lymphoma.
AB  - BACKGROUND: No immunohistologic techniques are currently available to demonstrate
      clonality of T-cell lymphomas. Monoclonal antibodies to the variable region of
      the T-cell receptor (TCR) have been produced that identify minor populations of
      normal peripheral blood T lymphocytes. OBJECTIVE: We investigated the expression
      of TCR V-region genes in cutaneous lymphomas to determine whether immunostaining
      with these antibodies may be a simple method to detect clonal T-cell
      proliferations and help to distinguish benign lymphoid infiltrates from malignant
      lymphoma. METHODS: Cutaneous samples were obtained from 18 cutaneous T-cell
      lymphomas (14 mycosis fungoides, 1 Sezary syndrome, 2 pleomorphic T-cell
      lymphoma, and 1 large cell anaplastic lymphoma) and 8 benign lymphoid
      infiltrates. Frozen sections were incubated with monoclonal antibodies and
      stained by the alkaline phosphatase-antialkaline phosphatase technique. Staining
      was performed with a panel of 7 anti-TCR V-region antibodies, 6 T-cell markers, 1
      anti-beta chain antibody, and 1 anti-delta chain antibody. RESULTS: Clonality
      could be demonstrated in 2 of 18 cutaneous lymphomas. We observed the strictly
      intraepidermal localization of clonal proliferation in one case of early-stage
      mycosis fungoides. CONCLUSION: Anti-TCR V-region antibodies may identify a
      strictly epidermotropic clone in early mycosis fungoides. However, the panel of
      antibodies currently available stains only a minority of cutaneous T-cell
      lymphomas. The usefulness of these antibodies as a clonotypic marker needs to be
      reevaluated when a larger panel of antibodies becomes available.

PMID- 1357012
TI  - Cardiovascular and renal effects of eel and rat atrial natriuretic peptide in
      rainbow trout, Salmo gairdneri.
AB  - The renal and in vitro vascular effects of atrial natriuretic peptides have been
      examined in several species of fish. However, comparatively few investigations
      have described the effects of these peptides on the cardiovascular system in
      vivo. In the present experiments the dorsal aorta and urinary bladder were
      cannulated and the effects of atrial natriuretic peptides from rat and eel were
      monitored in conscious trout during bolus injection or continuous atrial
      natriuretic peptide infusion. The results show that the initial pressor effect of
      atrial natriuretic peptides is independent of environmental salinity adaptation
      (fresh or seawater) and the chemical form of atrial natriuretic peptide injected,
      but it is affected by the rate of atrial natriuretic peptide administration. This
      pressor response, and the accompanying diuresis, are mediated through alpha
      adrenergic activation. Continuous infusion of either rat or eel atrial
      natriuretic peptide produces a steady fall in mean arterial blood pressure, which
      is temporally preceded by an increase in heart rate and a decrease in pulse
      pressure. Diuresis induced by atrial natriuretic peptides is only partially
      sustained during continuous infusion. Propranolol partially blocks the increase
      induced in heart rate by atrial natriuretic peptides, but does not affect either
      pulse pressure or mean arterial pressure. Propranolol significantly increases
      urine flow in saline-infused animals but has no apparent effect on animals
      subjected to infusions of atrial natriuretic peptides. These results indicate
      that there are multiple foci for the action of atrial natriuretic peptides in
      trout and that in many instances the effects of atrial natriuretic peptides are
      mediated through secondary effector systems.

PMID- 1357013
TI  - The effects of FMRFamide, 5-hydroxytryptamine and phorbol esters on the heart of
      the mussel Geukensia demissa.
AB  - The ventricle of the mussel Geukensia demissa is inhibited by 5-hydroxytryptamine
      and excited by the molluscan neuropeptide FMRFamide. Supra-threshold doses of
      amide result in marked positive chronotropy and inotropy within 5-15 s. 5
      Hydroxytryptamine at 10(-8) M produces diastolic arrest within 10 s. A 1-min
      exposure to FMRFamide (5 x 10(-8) M) results in a small increase in the
      cytoplasmic levels of adenosine 3',5'-cyclic monophosphate; shorter or longer
      exposures have no effect. The cAMP content of ventricles incubated in 5 x 10(-8)
      M 5-hydroxytryptamine for 1 min decreases by 2.3 pmol/mg protein; longer or
      shorter incubations have no effect. Treatment with forskolin results in 3- or 4
      fold increases in adenosine 3',5'-cyclic monophosphate, but forskolin has no
      effect on the mechanical activity of the ventricle. The levels of inositol
      monophosphate, inositol 1,4-diphosphate, and inositol 1,4,5-triphosphate in
      tissues exposed to 5-hydroxytryptamine are not different from levels in control
      tissues. FMRFamide decreases the levels of these phosphoinositides by 50% or
      more. Lower concentrations of phorbol 12,13-diacetate (10(-8) to 10(-7) M) and
      phorbol 12-myristate,13-acetate (10(-6) M) cause positive chronotropy in the
      isolated ventricle; higher concentrations induce systolic arrest. These results
      suggest that the effects of 5HT on the ventricle are not mediated by adenosine
      3',5'-cyclic monophosphate or inositol 1,4,5-triphosphate. The effects of
      FMRFamide may involve a decrease in inositol 1,4,5-triphosphate. The effects of
      amide may involve a decrease in inositol 1,4,5-triphosphate. The response of the
      ventricles to phorbol esters suggest that protein kinase C may be involved in the
      regulation of cardiac contractility.

PMID- 1357015
TI  - Separate and additive stimulation of bovine milk yield by the local and systemic
      galactopoietic stimuli of frequent milking and growth hormone.
AB  - Lactating heifers were treated for 4 weeks with recombinant bovine growth hormone
      (bGH, n = 9) or were untreated (n = 9). In addition, two mammary glands of each
      heifer were milked four times daily rather than the normal twice daily for the
      same 4 weeks, and for the following 2 weeks. Over the 4 weeks, milk yield was
      increased 12.8% by bGH, 14.0% by frequent milking and 28.5% by the combined
      treatment. The effect of bGH as administered here was slower in onset than that
      of frequency, but eventually produced a higher peak yield. ANOVA revealed
      significant effects of each stimulus independently and an additive, but not
      synergic effect of the combined treatment. The effect of the combined treatment
      tended to persist beyond the end of treatment; most of this response was related
      to the milking frequency component rather than the bGH. Mammary differentiation
      was assessed in biopsies of mammary tissue obtained prior to and at the end of
      treatment. Mammary enzyme activities (expressed on a per cell basis) indicated
      minimal differentiative response to either treatment, but synthesis rates for
      lactose and casein determined in vitro were increased by bGH treatment.
      Histological examination revealed a stimulatory effect of milking frequency on
      epithelial cell size. The results indicate that these two galactopoietic stimuli
      operate through independent mechanisms, and neither stimulus alone is sufficient
      to maximize milk yield in dairy heifers.

PMID- 1357014
TI  - Cutaneous myelofibrosis.
AB  - Cutaneous extramedullary hematopoiesis is rare, usually occurring in neonates
      following intrauterine viral infections, hereditary spherocytosis, or the twin
      transfusion syndrome. Only 20 cases of cutaneous extramedullary hematopoiesis
      have been reported in adults, all with myelofibrosis. The cutaneous infiltrates
      may be atypical and difficult to distinguish from leukemia cutis. We have studied
      a 65-year-old woman with myelofibrosis and approximately 40 violaceous, firm, non
      tender cutaneous nodules measuring 1 to 4 cm in diameter, located on her abdomen
      near a splenectomy scar. Histologically, the lesions had a dense infiltrate of
      myeloid cells in all stages of maturation, atypical large cells with multilobate
      nuclei or multiple nuclei, resembling atypical megakaryocytes, and fibroblasts.
      Although the patient received erythropoietin therapy prior to the development of
      the nodules, erythroid progenitors were not seen. Reticulin was increased
      particularly surrounding the atypical megakaryocytes. The myeloid cells stained
      for chloroacetate esterase and with the polyclonal antibody MAC 387. Atypical
      megakaryocytes stained for Factor XIIIa and Factor VIII-related antigen.
      Dendritic Factor XIIIa positive cells were also increased. The skin lesions
      remain unchanged grossly one year after their development.

PMID- 1357017
TI  - Special issue: IADR Abstracts.

PMID- 1357016
TI  - Heterogeneity of surfaces of subgingival bacteria as detected by zeta potential
      measurements.
AB  - Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus
      actinomycetemcomitans (A.a.) are Gram-negative bacteria which are implicated in
      various forms of periodontal disease. The Gram-positive Peptostreptococcus micros
      may also play an important role. For investigation of the possible adhesion and
      colonization mechanisms of these organisms, the charge properties of the
      outermost layers of bacterial cell surfaces were studied through the measurement
      of zeta potentials at various pH values. Eleven fresh clinical isolates,
      representing the four species, and one laboratory strain, P. gingivalis W83, were
      examined. Eleven of the 12 strains displayed heterogeneity with respect to pH
      dependent zeta potentials. Within single cultures of each of these strains, two
      distinct populations of cells were found, one which was more negatively charged
      than the other. For the Gram-negative strains, the more negatively charged
      subpopulation was in the majority, while the P. micros strains appeared to be
      composed mainly of a less-negatively-charged subpopulation. Vesicles prepared
      from two strains displayed the same pH dependence and heterogeneity of zeta
      potentials as the parent cells. An A.a. strain which was passaged several times
      in fluid medium had lost its fimbriae and became homogeneous with respect to
      charge.

PMID- 1357018
TI  - Lichen planus annularis: an immunohistochemical study.
AB  - Lichen planus annularis is a relatively rare skin manifestation of lichen planus.
      The mechanisms in the formation of annular lesions are not fully understood. We
      reported here a 57-year-old female with this disease. The eruption initially
      occurred as lichen-papules, then enlarged (bean-sized, umbilicated small
      plaques), and finally developed annular manifestations. We performed
      immunohistochemical examinations of specimens taken from different types of
      eruptions. In all specimens, HLA-DR was expressed in the focal keratinocytes
      adjacent to the dermal HLA-DR positive cell infiltration. Both in the initial
      papule and in the final annular lesion, expression of ICAM-1 was present only in
      the keratinocytes above the dermal cell infiltration, similar to HLA-DR. It is of
      interest that, in the umbilicated small plaques, the peripheral epidermis other
      than the central site extensively reacted to ICAM-1. LFA-1 expression was most
      prominent in the mononuclear cells impinging on the dermo-epidermal junction in
      all specimens. In addition, in the periphery of the umbilicated small plaques,
      which showed no bandlike dense cell infiltration nor degeneration of basement
      membrane, TNF-alpha, but not LFA-1, was positive in the infiltrated cells of the
      upper dermis. These results suggest that expressions of ICAM-1 and TNF-alpha in
      the peripheral keratinocytes and dermal infiltrated cells are important molecular
      events in the mechanisms of formation of the annular lesions.

PMID- 1357019
TI  - Correlation of bronchial eosinophil and mast cell activation with bronchial
      hyperresponsiveness in children with asthma.
AB  - Bronchial hyperresponsiveness in asthma has been associated with increased
      numbers of eosinophils and mast cells in the bronchial airway. It is unclear if
      these cells are important in the pathogenesis of hyperresponsiveness, and the
      role of mast cells has been discounted because they are effectively stabilized by
      beta-adrenergic drugs. Because the pathogenesis of asthma in children may be
      different from that in adults, and to find out if cellular activation is
      associated with bronchial reactivity, we studied 17 children with mild to
      moderately severe chronic asthma who had been treated with intermittent
      brochodilator therapy and compared their bronchial responsiveness to histamine
      with the levels of eosinophil cationic protein and mast cell tryptase in
      broncholavage fluid. The number of eosinophils in lavage fluid was correlated
      with histamine responsiveness (r = -0.444, p < 0.05) but not with levels of
      cationic protein (r = 0.33, p = NS). Bronchial responsiveness to histamine was
      highly correlated with mast cell tryptase (r = -0.714, p < 0.005), but there was
      no correlation with eosinophil cationic protein (r = -0.355, p = NS). We conclude
      that in children with chronic asthma mast cells as well as eosinophils contribute
      to bronchial hyperresponsiveness. Activated mast cells may play a primary role,
      possibly by tryptase-induced upregulation of bronchial smooth muscle tone.

PMID- 1357020
TI  - Influence of long-term hypoxia on tyrosine hydroxylase in the rat carotid body
      and adrenal gland.
AB  - Tyrosine hydroxylase (TH) protein was measured in the carotid body and adrenal
      gland of rats exposed to normobaric hypoxia (10% O2 in nitrogen) for 3, 7, 14 or
      22 days. After 22 days of hypoxia, a gradual increase in TH protein content was
      observed in the carotid body and in the adrenal gland, reaching 168% and 148% of
      the normoxic controls, respectively. To determine if the increase in TH protein
      content in the carotid body could alter catecholamine biosynthesis, in vitro TH
      activity and catecholamine turnover were measured in rats submitted to hypoxia
      for 14 days. TH activity was increased by 11.2-fold, while the turnover of
      dopamine and norepinephrine was increased by 14.8- and 5.4-fold, respectively.
      The data show that long-term hypoxia exerts a stimulatory influence on TH protein
      in the carotid body and adrenal gland in addition to an elevation in dopamine and
      norepinephrine biosynthesis in the carotid body.

PMID- 1357021
TI  - Acetylcholine receptors in rat cardiac neurones.
AB  - Membrane potential changes produced by acetylcholine (ACh), and their underlying
      mechanisms, were studied in neurones of isolated cardiac ganglia of the rat by
      means of intracellular microelectrodes. Five components of membrane potential
      change could be detected in cardiac neurones following 1-5 s micro-application of
      ACh: (i) fast depolarization resulting from an activation of nonselective
      cationic conductance; (ii) slow depolarization associated with a decreased
      membrane conductance, presumably for potassium ions; slow hyperpolarization which
      consisted of (iii) early and (iv) late parts resulting from an activation of
      calcium-sensitive potassium current and from inhibition of steady-state inward
      current, respectively; and (v) delayed slow hyperpolarization associated with an
      increased conductance, most likely for potassium ions. Components (i), (iii) and
      (iv) persisted in the presence of atropine and were inhibited by nicotinic
      antagonists. Thus they were due to activation of nicotinic ACh receptors.
      However, the sensitivity of component (i) to ganglion-blocking agents appeared to
      be rather low: IC50s for inhibiting (i) were 226 +/- 34.2 microM, 31.2 +/- 4.31
      microM and 15.3 +/- 3.27 microM for hexamethonium, d-tubocurarine, and
      trimetaphan, respectively. Components (ii) and (v) were abolished by atropine (1
      microM) and mimicked by muscarine (component (ii) also persisted in d
      tubocurarine), hence they resulted from activation of muscarinic ACh receptors.
      It is concluded that cardiac neurones are endowed with both nicotinic and
      muscarinic ACh receptors. Their activation leads to membrane depolarization and
      discharges followed by hyperpolarization and inhibition of discharges.

PMID- 1357022
TI  - Biochemical, autoradiographic and functional studies on a unique glutamate
      binding site in adrenal gland.
AB  - L-Glutamate is known to function as a major excitatory neurotransmitter in the
      mammalian central nervous system, and recent reports suggest the existence of
      receptors for glutamate in several peripheral tissues. In the present study, the
      characteristics of the binding of [3H]L-glutamate to sections of bovine adrenal
      gland were studied, and the localisation of this binding was investigated in
      adrenal glands from cow, dog, rat and guinea pig. In addition, the effects of
      glutamate on catecholamine release from the perfused isolated bovine adrenal
      gland were investigated. Binding of [3H]L-glutamate to slide-mounted sections of
      bovine adrenal gland was of high affinity (Kd 0.4 microM), rapid, saturable,
      reversible, stereospecific and to a single population of sites. The
      pharmacological profile of this binding site appeared to be unique, and did not
      correspond to any of the central receptor subtypes for glutamate so far
      identified. In the adrenal gland of the cow, rat and guinea pig, the binding
      density of [3H]L-glutamate was higher in cortex than medulla, while this pattern
      was reversed in the canine adrenal gland. Glutamate had no effect on the basal
      secretion of noradrenaline or adrenaline from the perfused isolated bovine
      adrenal gland, and neither glutamate nor the glutamate receptor antagonist
      kynurenate altered the nicotine-stimulated release of these catecholamines. These
      results suggest the existence of a novel peripheral binding site for glutamate in
      the adrenal gland. The differential autoradiographic localisation of this binding
      site in the adrenal glands of the various species studied may reflect different
      functional properties of glutamate in these species, and suggests possible roles
      for glutamate in the modulation of adrenal function.

PMID- 1357023
TI  - Review of the management of open fractures.
AB  - This article presents a literature review of the evaluation and management of
      open fractures. A case report of a patient having sustained a type II open
      fracture of the hallux is presented. Debridement, tetanus prophylaxis, reduction
      and stabilization, and intravenous antibiosis are the hallmarks for prompt and
      appropriate treatment.

PMID- 1357024
TI  - The potentiation of narcotic analgesics with phenothiazines.
AB  - Potentiation of narcotic analgesics with phenothiazines have been used for
      preoperative and postoperative analgesia for a number of years by the podiatric
      community. The agents most frequently cited in studies are the combination of
      meperidine with either the phenothiazines chlorpromazine, trimeprazine, or
      promethazine. Due to the fact that the double-blind clinical studies of pain are
      mainly subjective, and difficult to quantify, the usefulness of phenothiazines
      for the sole purpose of potentiation of analgesia is questionable, especially in
      view of the many side effects of this group of drugs.

PMID- 1357026
TI  - Ontogenetic transition of cardiac myosin heavy chain isoforms in rat ventricle:
      effects of fetal exposure to beta-adrenergic agonists or antagonists.
AB  - Cardiac myosin heavy chain (MHC) expression undergoes an ontogenetic transition
      from beta to alpha MHC isoforms. Although thyroid hormone plays a role in this
      change, the timing of the events suggests the participation of other factors.
      Using a new, denaturing SDS-PAGE procedure that cleanly resolves the beta and
      alpha heavy chains, we have assessed the role of beta-adrenergic stimulation on
      this transition in fetal and neonatal rat hearts. In control animals at embryonic
      day 20, less than 15% of the MHC was the alpha-form, and the proportion increased
      to approximately 35% by postnatal day 1 and to 80% by postnatal day 8. Although
      catecholamine levels rise abruptly at birth, and cyclic AMP levels increase the
      expression of alpha-MHC in vitro, neither premature beta-adrenergic stimulation
      (maternal treatment with terbutaline on embryonic days 17, 18 and 19) nor
      continuous prenatal blockade of beta-receptors (maternal propranolol infusions
      from embryonic day 7 onward) influenced the developmental profile. Because beta
      receptors in fetal and neonatal heart are functionally linked to adenylate
      cyclase, and cyclic AMP has been shown to promote the expression of alpha-MHC,
      the lack of effect of terbutaline or propranolol suggests that activation of
      adenylate cyclase through fetal cardiac beta-receptors is not sufficient to
      mediate the switchover without participation of other factors, such as thyroid or
      steroid hormones, or hypoxia.

PMID- 1357025
TI  - Inhibition of metabolic activity of polymorphonuclear granulocytes by thyroid
      stimulating antibodies.
AB  - Both thyrocytes and polymorphonuclear granulocytes (PMNs) are known to have on
      their surface thyrotropin receptor (TSH-R). Anti-TSH-R antibodies having
      stimulating and blocking effects on thyroid function have been detected in sera
      of Graves' patients. Thyroid stimulating anti-TSH-R antibodies (TSAb) are
      involved in the pathomechanism of thyrotoxicosis. The basic question is in this
      study whether TSAb exerts effects on metabolic activity of PMNs. Immunoglobulin G
      (IgGs) of 32 patients with thyrotoxicosis had significant inhibitory effect (p
      less than 0.001) on chemiluminescence of healthy PMNs compared to controls. An
      inverse correlation was observed between inhibitory effect of IgGs on function of
      PMNs and TT4 (r = -0.61) in contrast to anti-TSH-receptors antibodies (r = 0.09).
      TSAbs of eight hyperthyroid patients were measured by determination of cyclic AMP
      in suspension and slices of porcine thyroid gland. Function of human PMNs
      separated from healthy donors was determined by luminol-amplified
      chemiluminescence. Photon-emission of PMNs induced by adherence was significantly
      lower than that of controls. None of patients' IgGs contained anti-PMNs
      antibodies or other toxic compounds. It was found an inverse correlation between
      chemiluminescence of PMNs and capability of TSAb to increase intracellular cAMP
      in thyroid slices and the thyroid hormone levels of patients with thyrotoxicosis
      (p = 0.0005). In conclusion, TSH-R on PMNs did not belong to "mute" receptors and
      metabolic changes in PMNs induced by TSAb might have pathogenetic as well as
      methodological implications.

PMID- 1357027
TI  - Discordant segregation of Na+,K(+)-adenosine triphosphatase alleles and essential
      hypertension.
AB  - OBJECTIVES: To determine whether the alpha 2 and or beta 1 isoforms of the
      Na+,K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) are involved in the
      pathogenesis of essential hypertension. DESIGN: Segregation analysis of
      polymorphic DNA markers was used to test the involvement of Na+,K(+)-ATPase in
      essential hypertension. PARTICIPANTS: Children with persistent hypertension
      having one parent with essential hypertension were included in the study.
      Criteria for persistent hypertension were blood pressure readings with systolic
      and/or diastolic levels exceeding the 95th percentile based upon age and sex. The
      diagnosis of hypertension for adults, including parents and older siblings, was
      confirmed using criteria recommended in the 1988 report of the Joint National
      Committee on Detection, Evaluation, and Treatment of High Blood Pressure.
      RESULTS: In three essential hypertensive families consisting of 18 members
      including 11 hypertensives, several obligate recombinants between the Na+,K(+)
      ATPase alpha 2 isoform marker and the hypertension phenotype were observed.
      Similarly, in one hypertension family consisting of four members, obligate
      recombinants between the beta 1 isoform marker and the disease were observed.
      CONCLUSIONS: The discordant segregation of the alpha 2 and beta 1 isoform markers
      and essential hypertension suggests that neither the Na+,K(+)-ATPase alpha 2 nor
      beta 1 isoform genes play a primary role in the pathogenesis of hypertension in
      the families studied.

PMID- 1357028
TI  - The frequency of alpha 2-adrenoceptor restriction fragment length polymorphisms
      in normotensive and hypertensive humans.
AB  - OBJECTIVE: To examine the frequency of distribution of allelic polymorphisms of
      the alpha 2-adrenoceptor gene in normotensive and hypertensive humans. DESIGN:
      The frequency of alpha 2-adrenoceptor genotypes was compared in the two groups
      using the chi 2-test. SETTING: The Midwest Hypertension Research Center
      Outpatient Clinic of Creighton University School of Medicine. STUDY PARTICIPANTS:
      History was taken from and physical examination performed on each of the 60
      hypertensive and 47 normotensive adults. METHODS: DNA was extracted from
      leukocytes from each participants. Twenty restriction endonucleases were used and
      one restriction fragment length polymorphism (RFLP) was found using a 950-bp
      restriction fragment from the coding region of the human platelet alpha 2
      adrenoceptor gene (ADRA2R) and Bsu36I restriction endonuclease. This probe and
      Bsu36I restriction endonuclease, in addition to another restriction endonuclease
      (Dra I), were then used in the study. RESULTS: Three genotype patterns were
      found. Homozygotes for the Bsu36I RFLP have either a unique 12-kb or a unique 5.8
      kb band. Heterozygotes have both bands. The frequency of this alpha 2
      adrenoceptor RFLP was calculated. In hypertensives the frequencies of the 12- and
      5.8-kb alleles were 0.52 and 0.48, compared with 0.45 and 0.55, respectively, in
      normotensive, a difference that was not statistically significant. CONCLUSIONS:
      The frequency of the Bsu36I RFLP involving an alpha 2-adrenoceptor gene in
      hypertensives did not differ significantly from that in normotensives. A genetic
      linkage study is now under way to test for an association of the Bsu36I RFLP of
      the alpha 2-adrenoceptor gene with essential hypertension in families.

PMID- 1357029
TI  - Changes in the precursor frequencies of IL-4 and IFN-gamma secreting CD4+ cells
      correlate with resolution of lesions in murine cutaneous leishmaniasis.
AB  - Limiting dilution analysis was used to estimate the frequency of clonogenic Ag
      specific CD4+ T lymphocytes in draining lymph nodes of mice over the course of
      infection with Leishmania major, and to measure the production of IL-2, IL-3, IL
      4, IFN-gamma, and TNF by the resultant clones. Infection of both genetically
      susceptible BALB/c ("non-healer") and resistant C57BL/6 ("healer") mice resulted
      in at least a fourfold increase in the frequency (to about 0.3%) and at least a
      10-fold increase in the total number of lymph node CD4+ cells that formed clones
      when cultured with L. major Ag in vitro. At 1 wk after infection, the majority of
      clones from BALB/c mice secreted IL-4 (precursor frequency 0.15%) and fewer
      secreted IFN-gamma (0.05%); this pattern remained constant for at least 8 wk
      after infection. In C57BL/6 mice, however, a high precursor frequency of IL-4
      secreting clones was measured in the first 1 to 2 wk when the mice had lesions,
      but resolution of infection was associated with a decrease in the frequency of IL
      4-secreting clones (from 0.13% at 2 wk to 0.03% at 4 wk) and an increase in the
      frequency of IFN-gamma-secreting clones (from 0.08% to 0.22%). At all stages of
      infection, most clones from either mouse strain secreted IL-3 and very few
      secreted TNF. Analysis of PCR-amplified cDNA from draining lymph nodes of
      infected mice also revealed that IL-4 and IFN-gamma mRNA were expressed in both
      mouse strains early in infection. IL-4 mRNA was the major species at 2 and 6 wk
      after infection in BALB/c mice, but declined relative to IFN-gamma mRNA over this
      time in C57BL/6 lymph nodes. Precursor frequency estimates of lymphokine
      secreting CD4+ cells in draining lymph nodes therefore correlated with lymphokine
      expression patterns in vivo. Analysis of a panel of individual short term clones
      derived from mice 1 wk after infection revealed marked heterogeneity in
      lymphokine production patterns. In BALB/c mice, 49% secreted IL-4 without IFN
      gamma, 18% secreted IFN-gamma without IL-4, and 14% secreted both IL-4 and IFN
      gamma. Similarly in C57BL/6 mice, 39% secreted IL-4, 20% secreted IFN-gamma, and
      17% secreted both lymphokines. Many of the clones also produced IL-3 and/or IL-2.
      Together the data suggest that both IL-4 and IFN-gamma are synthesized early in
      infection of susceptible and resistant mice as assessed by mRNA and precursor
      frequency analyses.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1357030
TI  - Anergic Th1 cells express altered levels of the protein tyrosine kinases p56lck
      and p59fyn.
AB  - Tolerance in T lymphocytes can result from clonal anergy, or paralysis, of Ag
      specific T cells. To investigate the molecular mechanisms responsible for anergy,
      a system in which tolerance can be induced in vitro was employed. Anergy, as
      defined by long-lived nonresponsiveness to normal antigenic stimulation for IL-2
      production, was produced in cloned murine CD4+ Th1 cells. Here we report that
      such anergic Th1 cells express constitutively reduced amounts of the protein
      tyrosine kinase p56lck and constitutively elevated levels of the protein tyrosine
      kinase p59fyn. Because protein tyrosine phosphorylation is known to be important
      for the normal induction of IL-2 synthesis, these results suggest that T cell
      anergy may be maintained, at least in part, by alterations in tyrosine
      phosphorylation signaling events.

PMID- 1357031
TI  - Restriction fragment length polymorphism of the murine C4 and Slp genes: two C4
      groups.
AB  - We have examined the related H-2 genes coding for the fourth component of
      complement (C4) and the sex-limited protein (Slp) from 30 inbred mouse strains by
      Southern blot analysis. With four restriction enzymes, 11 RFLP patterns
      distributed among 26 different H-2 haplotypes have been identified. Strains of
      the same serologic H-2 haplotype were found to have identical RFLP patterns. It
      was confirmed that the number of C4-related genes in most haplotypes is two, Slp
      and C4; but H-2SWI6 (SWI6) and SWI9, which have the same RFLP pattern, have four
      and Sw7 has five. Although C4 and Slp have many similarities, they also were
      found to contain distinctive features: relative to Slp, each C4 allele examined
      has two insertions totaling 1.1 kb located in introns 14 and 15; and each Slp
      allele examined, excluding hybrids, has a provirus insertion upstream. No other
      large deletions or insertions were detected. The RFLP patterns are also due to 10
      polymorphic restriction sites, which have been placed on standard maps; two are
      associated with Slp and eight are associated with C4.Sk strains, the only strains
      that express low serum levels of C4, have the same RFLP phenotype as Sw14, Sw18,
      and Swx; Sk may have arisen from a recent common ancestor of these strains.
      Homologous recombination has been important in the formation of existing C4
      alleles. However, based on complete linkage disequilibrium between three RFLP
      internal to C4, the haplotypes have been divided into two groups that may have
      functional significance.

PMID- 1357032
TI  - High levels of IL-2 alter signal transduction in cloned IL-4-producing CD4 T
      cells.
AB  - Cloned CD4 T cells of the Th2 type make IL-4 and related cytokines upon receptor
      cross-linking, whereas cloned CD4 T cells of the Th1 type make IL-2, IFN-gamma,
      and TNF-beta. These two types of CD4 T cell are also reported to use distinct
      mechanisms of signal transduction. It has been reported that Th1 cells flux Ca2+
      upon receptor cross-linking, whereas Th2 cells do not. We have noted that when
      cloned Th2 cells are exposed to high levels (20 U/ml) of IL-2, they show an
      altered phenotype. Such cells are much more sensitive to activation by certain
      antireceptor antibodies, they flux calcium upon receptor ligation without
      additional cross-linking with anti-Ig antibodies, and they make much larger
      amounts of IL-4. In addition, the organization of their TCR is altered, with
      increased levels of the TCR-eta chain and an increase in the extent of
      association of CD4 with CD3 and CD45, changes similar to those found in Th1
      cells. These results suggest that there is no fundamental difference in the
      signal transduction apparatus of Th1 and Th2 cells; rather, the IL-2 made by Th1
      cells may create similar phenotypic changes in these cells and thus create the
      impression of altered signal transduction mechanisms. These results do show that
      exposure to high levels of IL-2 can profoundly affect signal transduction in T
      cells. Furthermore, we found that the Ca2+ signal caused by CD3 antibodies seemed
      to differ in character from that caused by TCR antibodies suggesting that the use
      of CD3 antibodies is not always a good model for activation through the TCR.

PMID- 1357033
TI  - Depletion of CD4+ T cells but not inhibition of the protective activity of IFN
      gamma prevents cure of toxoplasmosis mediated by drug therapy in mice.
AB  - Toxoplasmosis is a frequent opportunistic infection in patients with AIDS. In
      these patients the major immune deficiencies are a severe depletion of CD4+ T
      lymphocytes and an impaired capacity to produce IFN-gamma. A mouse model was
      developed and used to study the effects that depletion of CD4+ T cells and/or
      inhibition of the protective activity of IFN-gamma have on the effectiveness of
      the drug therapy for toxoplasmosis. Infection of mice with a lethal inoculum of
      Toxoplasma gondii cysts followed by treatment with the hydroxynaphthoquinone
      566C80 or with sulfadiazine resulted in 100% survival whereas untreated controls
      had 100% mortality within 15 days of infection. Administration of antiserum to
      IFN-gamma resulted in early death of untreated mice and in 30% mortality in those
      treated. Administration of mAb to CD4+ T cells followed by infection with T.
      gondii prevented the development of both antibody and cell-mediated immune
      responses against the parasite. These mice resisted the acute infection while
      undergoing specific treatment. Discontinuation of the treatment, however,
      resulted in reactivation of the infection and the majority of the animals died
      within 17 days of suspension of the treatment. Administration of antiserum to IFN
      gamma or to CD4+ T cells 24 h but not 15 days after conclusion of the treatment
      also resulted in mortality. These results indicate that successful treatment of
      toxoplasmosis depends on the status of the immune system, particularly of CD4+ T
      cells. Although it is speculative to compare results obtained in mice to the
      situation in humans, our work suggests that restoration of a competent immune
      response is of crucial importance for a successful treatment of toxoplasmosis in
      immunocompromised individuals.

PMID- 1357034
TI  - Predominance of Th1 cells in ocular tissues during herpetic stromal keratitis.
AB  - Herpetic stromal keratitis (HSK) appears to represent an immunopathologic
      response in the cornea of the eye to HSV-1. T cells of the CD4+ subset were shown
      to be involved in the mediation of HSK, but how they subserve an immunopathologic
      role is uncertain. In the present report, we have isolated cells from eyes in the
      active phase of HSK and studied their cytokine profile after culture in vitro or
      stimulation with Ag or nonspecific mitogens. Inflammatory cells recovered from
      eyes consist of polymorphonuclear leukocytes, macrophages, and lymphocytes. As
      reported before, all the lymphocyte recovered were of the CD4+ phenotype. After
      stimulation in vitro with Ag or mitogen the cytokines IL-2, IFN-gamma, and TNF
      alpha/beta were produced, but not the cytokines IL-4 and IL-10. Thus, on the
      basis of cytokine profile, ocular lymphocytes were identified as Th1 cells.
      Ocular cells were also stimulated with PMA and shown to produce IL-1. The results
      were discussed in terms of the possible means by which the Th1 cells induce
      tissue damage in HSK as well as in terms of the possible means by which a
      preferential accumulation of Th1 cell occurs in the eye.

PMID- 1357035
TI  - Selective decrease of CD26 expression in T cells from HIV-1-infected individuals.
AB  - The decrease of CD4+ cells in AIDS patients is widely documented, although the
      selective loss within different subsets of CD4+ cells and the mechanisms involved
      in this phenomenon are controversial. In the present report we have analyzed the
      proliferative response to Ag and mitogen of peripheral blood T lymphocytes from
      HIV-infected individuals, the phenotype profile of CD26+ and CD26- subset of
      cells and their infectivity by the HIV. The expression of CD26 Ag, either in CD4+
      or CD8+ cells, was clearly diminished in all the patients tested. On the other
      hand, the expression of CD29 seems not to be affected, nevertheless T cells from
      these patients were unable to generate a proliferative response against soluble
      Ag. In 11 out of 13 patients, polymerase chain reaction studies demonstrated that
      the CD26- subset of CD4+ cells was the main reservoir for HIV-1 in infected
      individuals and HIV-1 virus preferentially infected in vitro CD4+/CD26-
      subpopulation. This capacity for preferential infectivity, together with the
      selective loss of cells expressing CD26 Ag, helps to explain the progressive
      impairment in the immune system of these patients and sheds new light on our
      understanding of the AIDS pathophysiology.

PMID- 1357036
TI  - Development of murine lupus in CD4-depleted NZB/NZW mice. Sustained inhibition of
      residual CD4+ T cells is required to suppress autoimmunity.
AB  - Chronic administration of anti-CD4 mAb prevents autoimmune disease in NZB/NZW F1
      (B/W) mice. This may be due either to CD4 cell depletion or to inhibition of CD4
      cell function. To evaluate the relative importance of these mechanisms, we
      devised a system in which the consequences of cell depletion could be analyzed
      independent of the inhibitory effects of chronic mAb therapy. This was
      accomplished by performing adult thymectomy before mAb administration.
      Specifically, female B/W mice underwent thymectomy or sham thymectomy at age 6
      wk, followed at age 3 mo by a short course of either anti-CD4 (2 mg/wk for 3 wk)
      or saline. Treatment with anti-CD4 depleted 90% of circulating CD4 cells, but a
      small subpopulation (10%) of CD4 cells was refractory to depletion. In non
      thymectomized mice, the CD4 population gradually reconstituted after cessation of
      therapy. In contrast, in thymectomized mice, recovery of CD4 cells was prevented
      by the absence of the thymus. Despite the striking reduction in CD4 cells in
      thymectomized mice, severe autoimmune disease developed, with autoantibody
      levels, proteinuria, and mortality comparable with non-thymectomized, nondepleted
      controls. The unexpected development of lupus nephritis in thymectomized, CD4
      depleted B/W mice suggested that the thymus might be required to achieve the
      benefits of therapy with anti-CD4. To exclude this possibility, we demonstrated
      that chronic therapy with anti-CD4 prevents autoimmunity in thymectomized B/W
      mice. These findings imply that: 1) substantial depletion of CD4 T cells is not
      sufficient to suppress autoimmunity; 2) suppression of autoimmunity requires
      sustained functional inhibition of CD4 T cells; and 3) a small subpopulation of
      CD4 cells that is refractory to depletion by anti-CD4 is sufficient to promote
      the full expression of murine lupus in B/W mice.

PMID- 1357037
TI  - Consistency of routine measurements of CD4+, CD8+ peripheral blood lymphocytes.
AB  - In order to evaluate the reliability of CD4 and CD8 T lymphocyte counts in large
      scale studies, a quality control study was performed in 12 French laboratories.
      CD4 and CD8 counts, assessed by various haematological and immunological
      techniques, were compared in order to assess possible differences between the
      laboratories and the techniques used. Our data showed that (a) the consistency of
      CD4 measurements was satisfactory since the between-laboratory coefficient of
      variation for absolute CD4 cell numbers above 200/mm3 was around 15% instead of 5
      10% for all laboratories but one; (b) the major sources of variability arose from
      the use of automatic devices in the two-step measurement procedure:
      immunophenotyping and haematological counting. These data suggest that
      multicentre assays of CD4 and CD8 counts result in some increase in their
      variability. Nevertheless the results of large multicentric trials can be
      extrapolated with confidence in the routine care of HIV+ patients. Together, the
      results justified the involvement of several experienced laboratories in a
      clinical trial of HIV-related disease.

PMID- 1357038
TI  - Interaction of Citrobacter diversus strains with HEp-2 epithelial and human
      umbilical vein endothelial cells.
AB  - More than 75% of neonates with Citrobacter diversus meningitis develop brain
      abscesses. Interaction of C. diversus strains with HEp-2 and human umbilical vein
      endothelial cells (HUVEC) was studied to examine mechanisms related to brain
      abscess formation. Two of 9 strains invaded HEp-2 cells and 0 of 6 invaded HUVEC
      better than the others. C. diversus survived at least 20 h within HEp-2 cells (in
      decreasing numbers). Adhesion to HEp-2 cells was increased in 3 of 4 strains
      expressing type 1 fimbriae, but this did not correlate with increased invasion.
      Inhibition of RNA or protein synthesis blocked invasion but not adhesion. Thus,
      invasion requires ongoing protein synthesis, and adhesion to and invasion of HEp
      2 cells by type-1-fimbriated strains are independent steps. Invasion was
      inhibited by cytochalasin D. A 32-kDa protein found in cerebrospinal fluid
      isolates of C. diversus was not related to invasion of either cell line. Ability
      to invade HEp-2 cells was not increased among strains isolated from central
      nervous system sources.

PMID- 1357039
TI  - Escherichia coli in fecal flora of healthy adults: serotypes, P and type 1C
      fimbriae, non-P mannose-resistant adhesins, and hemolytic activity.
AB  - Escherichia coli strains from feces of 287 healthy adults were analyzed for O:K
      serotypes, P and type 1C fimbriae, non-P mannose-resistant adhesins, and
      hemolysin production. O1, O2, O6, O7, O18, O25, and rough-type lipopolysaccharide
      accounted for 40% of all isolates. K antigen was present in 62%; K1 was
      identified in 30% and K5 in 10%. O1, O2, O18, rough lipopolysaccharide, and P
      fimbriation were significantly associated with K1 and O6, O25, and type 1C
      fimbriation with K5. The overall prevalence of virulence-associated determinants
      was 22%; 7% of the strains possessed two or three of them. These determinants
      were most often associated with 9 serotypes (O1:K1, O2:K1, O6:K1, O6:K5, O7:K1,
      O16:K1, O22:K-, O25:K5, and R:K1) among which their prevalence was 43%, three
      times greater than among the remaining strains (P < .001). No enteropathogenic or
      enterohemorrhagic E. coli-associated serotypes were detected.

PMID- 1357040
TI  - [Chaperonins: highly conserved protein factors chaperoning other polypeptides].

PMID- 1357041
TI  - [The 65th Congress of the Japanese Biochemical Society. Fukuoka, Japan, October 9
      11, 1992. Abstracts].

PMID- 1357043
TI  - [Challenge to the cancer--choriocarcinoma].

PMID- 1357042
TI  - Early signs of carotid and iliac atherosclerosis in patients with severe
      hyperlipoproteinemia.
AB  - Hyperlipidemia is a major risk factor for atherosclerosis. Early signs of
      cardiovascular disease can be detected also in asymptomatic patients with
      hyperlipidemia. Forty-four patients with serum cholesterol greater than 300 mg/dl
      (7.8 mmol/l) and/or serum triglycerides greater than 500 mg/dl (5.6 mmol/l) and
      35 healthy controls had their carotid and iliac arteries examined by echo-Doppler
      with spectral analysis. Systolic ankle pressure was also measured. A vascular
      score was calculated: a 0 score was assigned to normal findings and a 1 score for
      each artery with abnormality at echo-Doppler or Winsor index less than 0.97. The
      XbaI Restriction Fragment Length Polymorphism of Apo B gene was investigated in
      all hyperlipidemic patients. Arterial lesions, especially those of internal
      carotid and iliac arteries, were more frequent (p less than 0.01) in patients
      with high serum lipids, compared to controls. Patients with lesions were older
      and had higher serum triglyceride concentrations compared to those without
      lesions. When divided according to serum triglycerides, patients with
      concentrations exceeding 200 mg/dl had higher vascular score (p less than 0.02)
      compared to those with serum triglycerides less than 200 mg/dl. No difference in
      restriction fragment length polymorphism (XbaI) of Apo B gene was demonstrated in
      patients with arterial lesions compared to those without lesions. Non-invasive
      echo-Doppler examination gives useful information on the arterial involvement of
      hyperlipidemic patients and its use should therefore be implemented, especially
      when high triglyceride concentrations are present.

PMID- 1357044
TI  - [Drug therapy of asthma by adrenergic beta receptor agonists and anticholinergic
      agents].

PMID- 1357045
TI  - [Regular use of inhaled beta-agonist and steroid in the therapy of asthma].

PMID- 1357046
TI  - [Asthma in the elderly].

PMID- 1357047
TI  - [Diagnosis, physiopathology and therapy of bronchial asthma: discussion].

PMID- 1357048
TI  - [A case of transient postpartum hypothyroidism due to thyroid stimulation
      blocking antibody activity].

PMID- 1357049
TI  - [Circulatory regulation mechanism of the central nervous system].

PMID- 1357050
TI  - [Multidrug resistance in leukemia and their treatment].

PMID- 1357051
TI  - DNA organization affects cellular radiosensitivity and detection of initial DNA
      strand breaks.

PMID- 1357052
TI  - The filter does not act as a DNA size discriminator in the neutral filter elution
      technique.
AB  - Various types of filters were used with the neutral filter elution technique. No
      significant differences in elution rate or curve shapes were found. Therefore we
      assume that the release of DNA fragments from the DNA gel formed by lysis of
      cells is the rate-determining event in elution and not the rate of migration
      through the filter. We suggest that the filter only serves as a support for the
      DNA gel.

PMID- 1357053
TI  - Effects of trypanothione on the biological activity of irradiated transforming
      DNA.
AB  - Held et al. (1984a,b) demonstrated previously that glutathione (GSH), a
      negatively charged thiol, is significantly less efficient in the hydrogen atom
      donation repair reaction with radicals induced by radiation in transforming DNA
      (t-DNA) than are other thiol compounds. Fahey et al. (1991a,b) postulated that
      the charge on thiols can influence their ability to radioprotect DNA. GSH, which
      is excluded from the vicinity of DNA due to its negative charge, is less
      protective than neutral or positively charged thiols. We have investigated this
      phenomenon further with trypanothione, the conjugate of glutathione and
      spermidine, N1,N8-bis (L-gamma-glutamyl-L-hemicystinyl-glycyl)-spermidine.
      Trypanothione exists in aerobic solution largely as the disulphide (T(S)2) but is
      maintained in the cell in the reduced form (T(SH)2) by means of an NADPH
      dependent flavo-enzyme, trypanothione reductase (TR). Experimental data show that
      T(S)2 in the presence of TR radioprotects t-DNA in the absence of oxygen much
      better than GSH or spermidine alone or in combination. Little radioprotection by
      T(S)2 is seen when TR is not present. The results obtained with reduced
      trypanothione at low concentrations suggest that radioprotection of t-DNA in
      hypoxia occurs predominantly by H atom donation and slightly by .OH radical
      scavenging, and the protection is greater than that by GSH or spermidine because
      the polyamine moiety in trypanothione allows a greater concentration of GSH near
      the DNA molecule.

PMID- 1357054
TI  - Effect of 2-deoxy-D-glucose on DNA double strand break repair, cell survival and
      energy metabolism in euoxic Ehrlich ascites tumour cells.
AB  - Effects of 2-deoxy-D-glucose (2-DG) on DNA double strand break (dsb) repair, cell
      survival and on the energy metabolism were investigated in exponentially growing
      Ehrlich ascites tumour (EAT) cells. Cells in suspension were exposed to 40 Gy of
      X-rays and allowed to repair (up to 4 h) with or without 2-DG at 37 degrees C.
      DNA dsb rejoining was measured by means of clamped homogeneous electric field
      (CHEF), a pulsed field gel electrophoresis technique. The fraction of activity
      released (FAR) during electrophoresis (DNA associated 14C-thymidine) was used as
      a parameter to determine the number of dsb present in the DNA. Biphasic kinetics
      for dsb repair were observed. The presence of 2-DG significantly inhibited the
      slow component of dsb repair. The presence of 2-DG also enhanced radiation
      induced cell killing. ATP content of cells was measured by a bioluminescence
      method. ATP content in exponentially growing cells was about 4 pg per cell. The
      level of ATP was reduced by 50% in presence of 2-DG (C2-DG/CG = 1.0).

PMID- 1357055
TI  - Synergistic effect of aphidicolin and 1-beta-D-arabinofuranosylcytosine on the
      repair of gamma-ray-induced DNA damage in normal human fibroblasts.
AB  - The effects on enzymatic DNA repair of aphidicolin and 1-beta-D
      arabinofuranosylcytosine (araC), two potent inhibitors of long-patch excision
      repair, were investigated in cultured human cells exposed to 60Co gamma
      radiation. Using alkaline-sucrose velocity sedimentation analysis, both drugs
      were shown to inhibit markedly the repair of radioproducts in cultures exposed to
      greater than or equal to 150 Gy, indicating that a significant component of gamma
      ray-induced DNA damage is operated on by a long-patch excision pathway. Moreover,
      while the extent of repair inhibited by aphidicolin was comparable to that
      suppressed by araC, combined exposure of irradiated cultures to the two drugs
      elicited a synergistic response. Specifically, in all three normal fibroblast
      strains examined, the yield of aphidicolin- or araC-detectable sites (lesions
      whose repair could be blocked by each drug alone) observed during the first 2 h
      after irradiation with 150 Gy ranged from 0.8 to 1.2 per 10(8) daltons genomic
      DNA, whereas the incidence of sites detected by combined exposure to the
      inhibitors was increased 4-fold (i.e. 3.8 per 10(8) daltons). This difference in
      site yield leads us to propose that simultaneous administration of aphidicolin
      and araC serves to block, in addition to long-patch repair, a second mode of
      excision repair which is refractory to each drug alone.

PMID- 1357056
TI  - Enhanced excision repair activity in mammalian cells after ionizing radiation.
AB  - Monkey CV-1 cells which had received 5 Gy 12 h before harvesting lysates from
      their cell cultures contained approximately three times as much DNA excision
      repair enzyme activity as unirradiated cells. The activity was determined in
      crude cell lysates by the release of intermediate mobility DNA fragments and
      fragments with 3'-phosphoryl ends from 5'-32P-end labelled irradiated 95 bp alpha
      DNA. Different 3'-termini endow the fragments with differing mobilities,
      signifying steps in the processing of radiation damaged DNA. Similar results were
      obtained when Krebs II mouse tumour cells growing in mice as ascites received 5
      Gy 12 h before harvest. The enzyme activities from CV-1 cells and from Krebs II
      cells were partially purified as 60-70 kDa proteins on Superose 12 or Ultrogel
      AcA-54 columns. Divalent cations were not required for enzyme activity. A 23
      nucleotide long defined duplex oligodeoxynucleotide substrate containing a single
      8-oxodG residue was also very actively cleaved by the partially purified cell
      enzymes. 8-oxoguanine is a major product of ionizing radiation's action on DNA
      and was recognized by the enzymes described here. The mechanism by which
      radiation increased excision repair activity of cellular enzymes is not
      understood.

PMID- 1357057
TI  - Hepatocyte response to continuous low dose-rate radiation in radioimmunotherapy
      assessed by micronucleus assay.
AB  - The response of hepatocytes to low dose-rate irradiation was examined in mice
      following the injection of radiolabelled monoclonal antibody. Mice were injected
      intravenously with an 131I-labelled monoclonal antibody 196-14 which recognizes
      CA125 antigen, and the effect of continuous low dose-rate irradiation on
      hepatocytes was assessed using the micronucleus assay. The frequency of
      micronuclei increased in a dose-dependent fashion, but it was lower than the
      frequency induced by conventional external X-rays which was determined
      immediately after the irradiation. A linear quadratic model (micronucleus
      frequency = aD+bD2+c) showed that the value of b decreased with low dose-rate
      irradiation from the radiolabelled antibody. It is concluded that the
      micronucleus assay is useful for the evaluation of the response of hepatocytes to
      irradiation in radioimmunotherapy.

PMID- 1357058
TI  - Modelling the formation of polycentric chromosome aberrations.
AB  - Exchange-type chromosome aberrations produced by ionizing radiation or
      restriction enzymes are believed to result from pairwise interaction of DNA
      double-strand breaks (dsb). In addition to dicentrics, such aberrations may
      include higher-order polycentrics (tricentrics, tetracentrics, etc.). We have
      developed computer programs that calculate the probability of the various
      polycentrics for a given average number of pairwise interactions. Two models are
      used. Model I incorporates kinetic competition between restitution, complete
      exchanges (illegitimate recombination events), and incomplete exchanges. Model II
      allows unrestituted breaks even if there is no recombination. The models were
      applied to experimental observations of aberrations produced in G1 Chinese
      hamster ovary cells after electroporation with the restriction enzyme PvuII,
      which produces blunt-end dsb. We found, experimentally and theoretically, that
      there was a maximum in the number and multiplicity of polycentrics per cell:
      beyond a certain PvuII concentration no additional or higher-order polycentrics
      were produced. Computer-generated relationships, which were remarkably similar
      for both models and for all values of the adjustable parameters, were found
      between dicentrics per cell and higher-order polycentrics per cell. Excellent
      agreement was found between the experimental observations and the consensus
      theoretical curve relating tricentrics per cell to dicentrics per cell. The
      observed number of higher polycentrics per cell for a given number of dicentrics
      per cell was somewhat larger than the consensus theoretical prediction. The
      observed number of centric rings per cell was markedly larger than the consensus
      theoretical value, presumably owing to intrachromosomal localization ('proximity
      effects'). The computer models also provided estimates for the adjustable
      parameters; for example, in model I the fraction of incomplete exchanges was
      found to be about 35%.

PMID- 1357059
TI  - Transformation and radiosensitivity of human diploid skin fibroblasts transfected
      with SV40 T-antigen mutants defective in RB and P53 binding domains.
AB  - A series of human diploid fibroblast cell clones were developed by DNA
      transfection with either wild-type SV40 T-antigen (SV40 T) or T-antigen mutants
      defective in its various functional domains. Cell clones expressing the wild-type
      SV40 T were significantly radioresistant as compared with clones transfected with
      the neo gene only (D0 = 192 +/- 13 vs 127 +/- 19). This radioresistance persisted
      in post-crisis, immortalized cell lines. A series of mutants with point or
      deletion mutations within each functionally active domain of SV40 T were also
      examined for their ability to alter radiosensitivity and induce morphological
      transformation. Cell clones transfected with T-antigen mutants defective in
      nuclear localization or origin binding showed increased radioresistance similar
      to clones transfected with wild-type T-antigen, and expressed morphological
      changes characteristic of SV40 T-transfected cells. A retinoblastoma
      susceptibility gene (RB) binding defective mutant showed moderately increased
      radioresistance (D0 = 174 +/- 10). However, cell clones transfected with three
      different p53 binding defective mutants showed no change in radiosensitivity (D0
      = 132 +/- 5) as compared with neo gene transfected controls. Transfection with T
      antigen mutants defective in either the RB or p53 binding domain yielded no
      morphological alterations characteristic of transformation. These data suggest
      that the SV40 T/p53 complex may be of importance in the radioresistance
      phenotype.

PMID- 1357060
TI  - Intrinsic radiosensitivity and PLD repair in osteosarcoma cell lines.
AB  - The response to radiation of seven osteosarcoma cell lines was analysed by in
      vitro colony-forming assay and compared with that of eight human fibroblast
      strains. The values of D0, the surviving fraction after 2 Gy (S2Gy), and the mean
      inactivation dose (D) of osteosarcoma cells in log-phase culture were
      significantly higher than those of fibroblast strains (p less than 0.01). PLD
      (potentially lethal damage) repair of osteosarcoma cells evaluated in the plateau
      phase of growth showed great variation for enhancement of survival, although all
      of the values were maximized within 12 h after irradiation. In the osteosarcoma,
      intrinsic radiosensitivity in vitro reflected the clinical response to radiation.
      However, the capacity for PLD repair might not be a good indicator for predicting
      the results of radiation therapy.

PMID- 1357061
TI  - Radiation-induced apoptosis of oligodendrocytes in vitro.
AB  - It has been suggested that glial cells and/or their progenitors are the primary
      target cells for radiation-induced demyelination. Cultures of terminally
      differentiated oligodendrocytes, immature oligodendrocytes, and O-2A progenitor
      cells were generated from the cerebral cortex and spinal cord of perinatal rat
      pups. Irradiation of cultures of terminally differentiated oligodendrocytes
      resulted in a significant increase in the percentage of apoptotic cells from 15%
      in control to 30% in irradiated samples, with the maximum increase induced by 10
      Gy. This increase in apoptosis could be observed by 1 h after irradiation with
      the maximum level reached at 3-6 h. Apoptotic cells were not detected before or
      after irradiation of cultures of O-2A progenitor cells or immature
      oligodendrocytes. These data suggest that radiation-induced apoptosis of
      terminally differentiated oligodendrocytes may be involved in early
      demyelination.

PMID- 1357062
TI  - Ascorbate-assisted, phthalocyanine-sensitized photohaemolysis of human
      erythrocytes.
AB  - The rate of photohaemolysis of human red blood cells sensitized by
      chloroaluminium phthalocyanine sulphonate is increased by ascorbate, with or
      without added FeCl3. Stimulation of haemolysis by ascorbate without addition of
      metal salt, and in the presence of a strong chelator such as desferrioxamine, is
      an unexpected phenomenon. Lysis rate and ascorbate concentration were directly
      related, suggesting that ascorbate acts as a reactant and not as a catalyst. The
      process also requires oxygen; azide and D2O tests indicate some participation of
      singlet oxygen, although to a lesser extent than in the photosensitized
      haemolysis in the absence of ascorbate. Kinetic considerations suggest a reaction
      path initiated by excited sensitizer and ascorbate, parallel to the singlet
      oxygen-mediated process. Because of the ubiquitous presence of ascorbate in human
      tissues in concentrations comparable to those of dissolved oxygen, it is quite
      possible that in photodynamic therapy a fraction of the photodynamic damage
      proceeds via a Type I, ascorbate-assisted, mechanism.

PMID- 1357063
TI  - The efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium
      and americium from the rat: comparison with other siderophore analogues.
AB  - With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has
      been tested for its ability to remove 238Pu and 241Am from rats after their
      inhalation or intravenous injection as nitrate. The most effective treatment
      regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3
      LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body
      were reduced respectively to 2 and 4% of those in untreated animals. These values
      were six and three times less than when DTPA was administered using the same
      protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally
      effective, the lung and total body contents being reduced respectively to 13 and
      10% of those in controls. Some animals showed slight degenerative changes in the
      liver and proximal tubules of the kidneys after the repeated administration of 30
      mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after
      DTPA treatment. After the intravenous injection of Pu, the most effective regimen
      was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7
      days was reduced to 7% controls compared with 19% after the repeated
      administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO
      was less effective owing to the higher retention of Pu in the liver. With
      repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for
      the decorporation of Am; the body contents were 16 and 31% of those in controls
      respectively. Importantly, the body content was still reduced to 28% of control
      after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is
      also superior to other siderophore analogues, could represent a most significant
      development in the decorporation of Pu and Am.

PMID- 1357064
TI  - Effects of lofexidine, an alpha 2-adrenoreceptor agonist, on ocular blood flow
      and ion transport of rabbit iris-ciliary body.
AB  - The effect of topical unilateral application of lofexidine, an alpha 2-agonist,
      on ocular regional blood flow was tested in anesthetized rabbits using
      radiolabeled microspheres. A significant reduction in blood flow was found only
      in the ciliary body of the treated eye at 1 hr after lofexidine treatment.
      However, the IOP of both eyes was decreased significantly at 30 and 60 min post
      lofexidine treatment. Yohimbine (i.v.) blocked this IOP lowering effect, but only
      partially prevented the blood flow response. In addition, no significant
      difference was found in either basal or amphotericin-B stimulated short-circuit
      current or potential difference of the isolated rabbit iris-ciliary body after 30
      minutes of lofexidine treatment. These observations suggest that the IOP lowering
      effect of lofexidine appears to be mediated by alpha 2-receptors but unrelated to
      the reduction in the ocular blood flow and net electrogenic ion transport.

PMID- 1357065
TI  - Studies on the mechanism of immunologic tolerance induction by murine dendritic
      epidermal Thy-1+ cell lines.
AB  - We are investigating the functions of the Thy-1+ dendritic cells present in
      murine epidermis. Dendritic epidermal Thy-1+ cell (DETC) lines conjugated in
      vitro with hapten induce specific immunologic tolerance upon intravenous (i.v.)
      or subcutaneous injection into the footpad of normal mice. In these studies, we
      demonstrate that hapten-conjugated cells of other long-term, interleukin-2 (IL-2)
      dependent, T cell lines are unable to induce tolerance upon footpad injection,
      indicating that the ability of DETC lines to induce tolerance is not a function
      of long-term cell culture or IL-2 dependence. Suppressor T cells were not found
      in mice made tolerant by footpad injection of hapten-conjugated cells of the DETC
      line AU16, although they could be demonstrated in mice made tolerant by i.v.
      injection. Studies of lymphocyte proliferation in vitro suggested that hapten
      conjugated AU16 cells may induce tolerance by inhibiting the proliferation of
      activated T lymphocytes.

PMID- 1357066
TI  - The 3rd Workshop on Nosocomial Infection Control. Proceedings. Bangkok, Thailand,
      July 12-14, 1989.

PMID- 1357067
TI  - Correlation between Ca(2+)-ATPase activity of rat islet cells and insulin
      secretion.
AB  - Using medium with a low ionic strength, a low concentration of Ca2+ and Mg2+ and
      devoid of K+, we have measured Ca(2+)-ATPase activity in the homogenates of rat
      islets preincubated for 3 min with several hormones in the presence of 3.3 mmol
      glucose/l. Insulin secretion was also measured in islets incubated for 5 min
      under identical experimental conditions. Islets preincubated with glucose (3.3
      mmol/l) and glucagon (1.4 mumol/l) plus theophylline (10 mmol/l), ACTH (0.11
      nmol/l), bovine GH (0.46 mumol/l), prolactin (0.2 mumol/l) or tri-iodothyronine
      (1.0 nmol/l) have significantly lower Ca(2+)-ATPase activity than those
      preincubated with only 3.3 mmol glucose/l. All these hormones increased the
      release of insulin significantly. Dexamethasone (0.1 mumol/l) and somatostatin
      (1.2 mumol/l) enhanced the Ca(2+)-ATPase activity while adrenaline (10 mumol/l)
      did not produce any significant effect on the activity of the enzyme. These
      hormones decreased the release of insulin significantly. These results
      demonstrated that islet Ca(2+)-ATPase activity was modulated by the hormones
      tested. Their inhibitory or enhancing effect seemed to be related to their effect
      on insulin secretion; i.e. those which stimulated the secretion of insulin
      inhibited the activity of the enzyme and vice versa. Hence, their effect on
      insulin secretion may be due, in part, to their effect on enzyme activity and
      consequently on the concentration of cytosolic Ca2+. These results reinforce the
      assumption that Ca(2+)-ATPase activity participates in the physiological
      regulation of insulin secretion, being one of the cellular targets for several
      agents which affect this process.

PMID- 1357068
TI  - Inhibitory action of somatostatin-14 on hormone-stimulated cyclic adenosine
      monophosphate induction in porcine granulosa and luteal cells.
AB  - Somatostatin-14 (SRIF-14) inhibited, in a concentration-dependent manner, LH- and
      forskolin-stimulated cyclic adenosine monophosphate (cAMP) induction in porcine
      granulosa and luteal cells. The inhibitory effect of SRIF-14 on hormone-induced
      cAMP generation was more potent in porcine ovarian cells than in the GH-3
      pituitary cell line. The inhibitory effect of SRIF-14 was impeded by neutralizing
      its biological activity with specific antiserum. Preincubation of luteal and
      granulosa cells with phorbol 12-myristate 13-acetate (PMA) enhanced LH- and
      forskolin-stimulated cAMP levels. SRIF-14 failed to inhibit LH- or forskolin
      stimulated cAMP levels in cells preincubated with PMA. It is concluded that SRIF
      14 inhibits hormone-stimulated cAMP induction in the porcine ovary. LH-induced
      protein kinase C activation may be physiologically important to alleviate the
      inhibitory effects of SRIF-14.

PMID- 1357069
TI  - Suramin affects differentiated and undifferentiated human thyroid epithelial
      cells in vitro.
AB  - In the last decade, suramin has become known for its antiproliferative,
      differentiation-inducing effects on cells and has been successfully used in the
      therapy of cancer patients. The present study was undertaken to investigate the
      effects of suramin on normal human thyroid cells in primary monolayer culture and
      to analyse whether it also affected cells from thyroid carcinomas. The results
      show that suramin, at concentrations similar to serum levels obtainable during
      therapy, inhibited the proliferation of thyroid cells as well as the secretion of
      thyroglobulin. It suppressed the activation of adenylyl cyclase in thyroid
      membranes and decreased the immunogenicity of the cells by reducing their surface
      expression of HLA-DR and ICAM-1. Although the morphology of differentiated
      thyroid cells remained unaffected by suramin, morphological changes compatible
      with differentiation were observed in cells from undifferentiated thyroid
      carcinomas when suramin was added to the culture medium. In conclusion, the data
      demonstrate that suramin has pronounced in-vitro effects on normal and neoplastic
      thyroid cells. It may, therefore, also be effective in patients with thyroid
      cancer, for whom no other form of treatment is available.

PMID- 1357070
TI  - Pyridostigmine partially reverses dexamethasone-induced inhibition of the growth
      hormone response to growth hormone-releasing hormone.
AB  - The GH response to insulin-induced hypoglycaemia and growth hormone-releasing
      hormone (GHRH) has been shown to be impaired in subjects with Cushing's syndrome
      and in healthy volunteers given oral glucocorticoids. Pyridostigmine is an
      anticholinesterase that stimulates GH secretion, probably by inhibition of
      hypothalamic somatostatin secretion. This work was designed to study the site of
      action of glucocorticoids in inhibiting the secretion of GH. Eight healthy male
      volunteers were studied on three occasions in random order. They took 2 mg oral
      dexamethasone or placebo at precisely 6-hourly intervals for 48 h before
      receiving 120 mg oral pyridostigmine or placebo, followed 60 min later by GHRH
      (100 micrograms) i.v. Samples for measuring GH were obtained at 15 min intervals
      for 2 h. The 'area under the curve' (AUC) for each of the treatments was
      significantly different: dexamethasone-pyridostigmine-GHRH (mean +/- S.E.M., 1938
      +/- 631 mU/min per l), dexamethasone-placebo-GHRH (634 +/- 211) and placebo
      placebo-GHRH (4267 +/- 1183) (P < 0.02, Wilcoxon test). In conclusion,
      dexamethasone given for 48 h significantly inhibited the AUC for GH following
      treatment with GHRH. However, pretreatment with pyridostigmine significantly
      reversed the inhibition although this was still partial. Our data suggested that
      this short-term suppressive effect of dexamethasone was independent of GHRH, and
      most probably relates to stimulation of the release of somatostatin.

PMID- 1357071
TI  - The effects of glutamate agonists on voltage-clamped motoneurons of the lobster
      cardiac ganglion.
AB  - The effects of L-glutamate and its analogues were studied in voltage-clamped
      motoneurons of the lobster cardiac ganglion. These excitatory amino acids caused
      a dose-dependent increase in membrane conductance and an inward current at the
      resting membrane potential. The EC50 for L-glutamate was 150 mumol 1(-1). The
      rank order of potencies of the various agonists was quisqualate greater than L
      glutamate = L-aspartate greater than kainate greater than cysteine. Kainate,
      unlike the other agonists, showed no desensitization. Of various antagonists
      studied, only the quinoxalinediones inhibited the response to glutamate. These
      antagonists also reduced the amplitude and duration of the pacemaker-driven burst
      potential, suggesting that glutamate may be released by some of the endogenous
      synapses within the ganglion. The reversal potential of the glutamate-induced
      current was -15 mV. When Na+ was replaced with K+, the glutamate-induced current
      still reversed between 0 and -20 mV. When Na+ was replaced with the impermeant
      ion N-methyl-D-glucamine, the current was inhibited. The amplitude of responses
      evoked by glutamate and its analogues was reduced in salines containing either
      high or low concentrations of Ca2+. These results of pharmacological and of
      reversal potential and ion substitution experiments indicate that glutamate acts
      on receptors of the non-NMDA (N-methyl-D-aspartate), quisqualate/kainate type to
      open a channel permeable to both Na+ and K+.

PMID- 1357072
TI  - Isolated left coronary ostial stenosis as the sole arterial involvement in
      Takayasu's disease.
AB  - A 24-year-old woman with Takayasu's disease developed unstable angina pectoris.
      Angiographic studies demonstrated an isolated left coronary ostial stenosis
      without any other systemic arterial involvement. She is unique in that the
      coronary lesion, which is rarely the major manifestation of Takayasu's disease,
      is the sole arterial involvement of the disease.

PMID- 1357073
TI  - Production of natural killer cell stimulatory factor (interleukin 12) by
      peripheral blood mononuclear cells.
AB  - Natural killer cell stimulatory factor (NKSF), or interleukin 12 (IL-12), is a 70
      kD heterodimeric cytokine composed of two covalently linked chains, p40 and p35.
      NKSF/IL-12 has multiple effects on T and NK cells and was originally identified
      and purified from the supernatant fluid of Epstein-Barr virus (EBV)-transformed
      human B lymphoblastoid cell lines. We have produced a panel of monoclonal
      antibodies against both chains of NKSF/IL-12. Some of these antibodies have
      neutralizing activity, and several combinations of them have been used to
      establish sensitive radioimmunoassays detecting the free p40 chain, the free p35
      chain, or the p70 heterodimer. Using these reagents, we have determined that most
      EBV-transformed human B lymphoblastoid cell lines constitutively produce low
      levels of the p70 heterodimer and an excess of the free p40 chain, whereas
      Burkitt lymphoma-derived, T, myeloid, and many solid tumor-derived cell lines
      produce neither. Production of both p40 and p70 is increased several-fold upon
      stimulation of the EBV-transformed cell lines with phorbol diesters. The ability
      of supernatant fluids from unstimulated and phorbol diester-stimulated cell lines
      to induce interferon gamma (IFN-gamma) production from T and NK cells, one of the
      effects of NKSF/IL-12, parallels the levels of production of the p70 heterodimer,
      known to be the biologically active form of NKSF/IL-12. Staphylococcus aureus
      Cowan I strain (SAC) and other stimuli induce accumulation of p40 mRNA and
      production of both p40 and p70 by peripheral blood mononuclear cells (PBMC). The
      producer cells appear to include both adherent cells and nonadherent lymphocytes,
      possibly B cells. The supernatant fluids from SAC-stimulated PBMC mediate the
      typical functions of NKSF/IL-12 (i.e., IFN-gamma induction, mitogenic effects on
      T/NK blasts, enhancement of NK cell cytotoxicity) at concentrations of p70
      similar to those at which recombinant NKSF/IL-12 mediates the same functions.
      Moreover, these activities are significantly inhibited by anti-NKSF/IL-12
      antibodies. The neutralizing anti-NKSF/IL-12 antibodies also inhibit 85% of the
      IFN-gamma production in response to SAC, an NKSF/IL-12 inducer, and approximately
      50% of the IFN-gamma production in response to non-NKSF/IL-12-inducers such as IL
      2, phytohemagglutinin, and anti-CD3 antibodies. These results indicate that
      induced or constitutively produced NKSF/IL-12 has a major role in facilitating
      IFN-gamma production by peripheral blood lymphocytes.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1357074
TI  - Response of naive antigen-specific CD4+ T cells in vitro: characteristics and
      antigen-presenting cell requirements.
AB  - Because of the low frequency of T cells for any particular soluble protein
      antigen in unprimed animals, the requirements for naive T cell responses in
      specific antigens have not been clearly delineated and they have been difficult
      to study in vitro. We have taken advantage of mice transgenic for the V beta 3/V
      alpha 11 T cell receptor (TCR), which can recognize a peptide of cytochrome c
      presented by IEk. 85-90% of CD4+ T cells in these mice express the transgenic
      TCR, and we show that almost all such V beta 3/V alpha 11 receptor-positive cells
      have a phenotype characteristic of naive T cells, including expression of high
      levels of CD45RB, high levels of L-selectin (Mel-14), low levels of CD44 (Pgp-1),
      and secretion of interleukin 2 (IL-2) as the major cytokine. Naive T cells,
      separated on the basis of CD45RB high expression, gave vigorous responses
      (proliferation and IL-2 secretion) to peptide antigen presented in vitro by a
      mixed antigen-presenting cell population. At least 50% of the T cell population
      appeared to respond, as assessed by blast transformation, entry into G1, and
      expression of increased levels of CD44 by 24 h. Significant contributions to the
      response by contaminating memory CD4+ cells were ruled out by demonstrating that
      the majority of the CD45RB low, L-selectin low, CD44 high cells did not express
      the V beta 3/V alpha 11 TCR and responded poorly to antigen. We find that
      proliferation and IL-2 secretion of the naive CD4 cells is minimal when resting B
      cells present peptide antigen, and that both splenic and bone marrow-derived
      macrophages are weak stimulators. Naive T cells did respond well to high numbers
      of activated B cells. However, dendritic cells were the most potent stimulators
      of proliferation and IL-2 secretion at low cell numbers, and were far superior
      inducers of IL-2 at higher numbers. These studies establish that naive CD4 T
      cells can respond vigorously to soluble antigen and indicate that maximal
      stimulation can be achieved by presentation of antigen on dendritic cells. This
      model should prove very useful in further investigations of activation
      requirements and functional characteristics of naive helper T cells.

PMID- 1357075
TI  - Challenges of space medical operations and life sciences management.
AB  - The Kennedy Space Center (KSC) has been the premier launch and landing site for
      America's space program since the early 1960s. Visitors are cognizant of space
      vehicles, processing facilities and launch pads which are treasured national
      resources. However, most are unaware of the unique organization which supports
      launch and landing activities and manages the center's occupational medicine,
      environmental health, ecological and environmental monitoring functions, as well
      as human and plant research programs. Management of this multifaceted
      organization can be complex because funding its different functions comes from a
      number of sources. Additionally the diverse disciplines of personnel present a
      special challenge in maintaining professional competencies while assuring
      efficiency in cyclical operations. This article explains the organization's
      structure and reviews some of its accomplishments.

PMID- 1357076
TI  - Controlled ecological life-support system. Use of plants for human life-support
      in space.
AB  - Scientists and engineers within NASA are conducting research which will lead to
      development of advanced life-support systems that utilize higher plants in a
      unique approach to solving long-term life-support problems in space. This
      biological solution to life-support, Controlled Ecological Life-Support System
      (CELSS), is a complex, extensively controlled, bioengineered system that relies
      on plants to provide the principal elements from gas exchange and food production
      to potable water reclamation. Research at John F. Kennedy Space Center (KSC) is
      proceeding with a comprehensive investigation of the individual parts of the
      CELSS system at a one-person scale in an approach called the Breadboard Project.
      Concurrently a relatively new NASA sponsored research effort is investigating
      plant growth and metabolism in microgravity, innovative hydroponic nutrient
      delivery systems, and use of highly efficient light emitting diodes for
      artificial plant illumination.

PMID- 1357077
TI  - An acetate-sensitive mutant of Neurospora crassa deficient in acetyl-CoA
      hydrolase.
AB  - The predicted amino acid sequence of the product of the acetate-inducible acu-8
      gene of Neurospora crassa, previously of unknown function, has close homology to
      the recently published sequence of Saccharomyces cerevisiae acetyl-CoA hydrolase.
      An acu-8 mutant strain, previously characterized as acetate non-utilizing, shows
      strong growth-inhibition by acetate, but will use it as carbon source at low
      concentrations. The mutant was shown to be deficient in acetyl-CoA hydrolase and
      to accumulate acetyl-CoA when supplied with acetate. As in Saccharomyces, the
      Neurospora enzyme is acetate-inducible.

PMID- 1357078
TI  - Characterization of Aeromonas sobria TAP13 pili: a possible new colonization
      factor.
AB  - Pili of Aeromonas sobria TAP13 were purified and characterized. The molecular
      mass of the pilin was estimated to be about 23 kDa by SDS-PAGE. The TAP13 pili
      were immunologically different from A. sobria Ae1 pili and A. hydrophila Ae6 W
      pili as previously reported, nevertheless all three had indistinguishable
      morphology and shared a high degree of homology in their N-terminal amino acid
      sequences. Strain TAP13 and its purified pili did not agglutinate human, rabbit
      or sheep erythrocytes. However, they adhered to rabbit intestine. Organisms
      pretreated with the Fab fraction of an antipilus antibody failed to adhere to
      rabbit intestine, and organisms did not adhere to intestine pretreated with
      purified pili. These results suggest that the pili are a colonization factor of
      A. sobria TAP13 for the rabbit intestine.

PMID- 1357079
TI  - Sequencing and analysis of the Bacillus subtilis lytRABC divergon: a regulatory
      unit encompassing the structural genes of the N-acetylmuramoyl-L-alanine amidase
      and its modifier.
AB  - The regulatory unit of Bacillus subtilis strain 168 encompassing the structural
      genes of the N-acetylmuramoyl-L-alanine amidase and of its modifier has been
      sequenced, and found to be a divergon consisting of divergently transcribed
      operons lytABC and lytR. Proteins LytA, LytB and LytC are endowed with export
      signal peptides. Mature LytA is a 9.4 kDa, highly acidic polypeptide whose
      deduced amino acid sequence points to a lipoprotein. LytB and LytC, the modifier
      and the amidase, are highly basic. After cleavage of the signal sequence their
      molecular masses are 74.1 and 49.9 kDa, respectively. These two proteins share
      considerable homology in their N-terminal moieties and have three GSNRY consensus
      motifs, characteristic of nearly all amidases. The C-terminal moiety of LytB
      exhibits homology to the product of spoIID. LytR is a 35 kDa protein which acts
      as an attenuator of the expression of both lytABC and lytR operons. Transcription
      of the lytABC operon proceeds from two promoters: PD, identified as P28-7 (Gilman
      et al., 1984), and an upstream PA. The former only is subject to LytR
      attenuation. Translational initiation of lytB and lytC is directed by UUG start
      codons, suggesting that lytA, B and C undergo coupled translation. Transcription
      of lytR is initiated at two start sites, one of which corresponds to a highly
      intense PA promoter whereas the other does not seem to share much homology with
      any of the known promoter consensus sequences. Both promoters are attenuated by
      LytR. It is confirmed that the synthesis of the amidase is controlled at least in
      part by SigD, i.e. that it belongs to the fla regulon and that its activity, or
      part of it, is co-regulated with flagellar motility. The role of the mutations
      conferring the Sin, Fla and Ifm phenotypes in the expression of the lytABC operon
      is discussed.

PMID- 1357080
TI  - Are Sinc and the PrP gene congruent? Evidence from PrP gene analysis in Sinc
      congenic mice.
AB  - Congenic mouse strains VM/Dk and VM-Sincs7/Dk differ at the Sinc gene, which
      controls the incubation period of scrapie in mice; VM/Dk mice are Sincp7p7 and VM
      Sincs7/Dk mice are Sincs7s7. Restriction fragment length polymorphism and DNA
      sequencing analysis demonstrated that the PrP genes also differ in these strains,
      confirming the close genetic linkage of Sinc and PrP. Using the restriction
      enzyme HhaI, we have shown that at least 100 kb of DNA flanking the PrP gene
      differs between the two strains, and therefore the congruence of the Sinc and PrP
      genes is still not certain.

PMID- 1357082
TI  - Serum antibodies to structural proteins of Hantavirus arise at different times
      after infection.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for the quantification
      of serum antibodies against group-specific epitopes of the glycoproteins (G1, G2)
      and nucleoprotein (NP) of the genus Hantavirus. This assay was used to study the
      kinetics of the development of serum antibodies after natural infection with
      Puumala-like virus in humans. To this end a panel of 34 serum samples collected
      from individuals at different times after natural infection was tested by the
      ELISA. The samples were also tested for specific IgM and IgG levels against
      Puumala-like virus, which provided confirmatory data about the presumed timing of
      infection. It was shown that serum antibodies against the G1 epitope were present
      in the acute and early convalescent period just before antibodies to the NP
      epitope could be demonstrated. In contrast, antibodies to two G2 epitopes were
      present not earlier than in the convalescent and late convalescent period. Since
      all these categories of antibodies seem to persist for long periods, antibodies
      against the G1 epitope and the NP epitope may be of specific diagnostic value.
      Furthermore, levels of G1-specific antibodies and antibodies to either NP or G2
      may allow estimation of the time elapsed following initial infection.

PMID- 1357081
TI  - Potential significance of the cellular immune response against the macaque strain
      of simian immunodeficiency virus (SIVMAC) in immunized and infected rhesus
      macaques.
AB  - The cellular immune response of seven rhesus macaques immunized with Tween-ether
      treated macaque strain of simian immunodeficiency virus (SIVMAC) and three non
      vaccinated control animals was investigated. Immunization elicited antigen
      specific proliferating CD4+ cells in five of seven monkeys. Proliferating T cells
      were found in all animals protected from a first virus challenge. Cytotoxic T
      lymphocytes (CTLs) were not induced by the immunization. After the second
      challenge, the four formerly protected animals became infected, despite a strong
      proliferative CD4+ cell activity in three of them. All animals lost their
      proliferative activity 2 weeks after infection. After the first challenge four of
      the six infected animals exhibited a CTL response and after the second challenge,
      one of four newly infected macaques acquired a CTL response. The five animals
      with a CTL activity against SIVMAC proteins were protected from severe
      thrombocytopenia, which appeared in the five CTL-negative animals after
      infection. Our data show the induction of proliferative T cells by immunization
      with soluble SIVMAC antigen. This T cell reactivity was found in all animals
      protected from the first virus challenge, but did not confer protection from the
      second challenge. Interestingly, the proliferative T cell reactivity disappeared
      2 weeks after virus infection. Furthermore a CTL response against viral proteins
      seems to protect infected animals from severe thrombocytopenia which is an early
      sign of AIDS in monkeys.

PMID- 1357083
TI  - Evaluation of a new generation synthetic peptide combination assay for detection
      of antibodies to HIV-1, HIV-2, HTLV-I, and HTLV-II simultaneously.
AB  - A new generation combination test (Detect-Plus, IAF BioChem, Montreal, Canada)
      based on synthetic peptides for HIV-1, HIV-2, HTLV-I, and HTLV-II was compared
      with three routine commercial screening assays and confirmatory assays to
      determine its sensitivity and specificity and to evaluate it as a substitute
      screening method. Samples from 356 sexually transmitted disease (STD) patients
      were tested by the four screening tests. All initially reactive samples were
      retested in duplicate by the corresponding EIA and repeatedly reactive samples
      were confirmed by Western blots for HIV-1, HIV-2, and HTLV-I/II. The confirmed
      positives detected by each screening assay were HIV-1 (23/356, 6.46%), HIV-2
      (11/356, 3.09%), and HTLV-I/II (5/356, 1.4%). The new generation Detect-Plus test
      produced only two results (2/356, 0.56%) that were presumed to be false-positives
      in comparison to the screening tests, but the OD/CO values were just slightly
      high (1.5 and 1.9). There were no false-negative results, indicating that the
      sensitivity of the new combination test was excellent (100%). Compared with
      routine retroviral EIA assays, the test is easy to perform--the total time
      requirement is only 2 hr and there is no need for incubation equipment. The OD/CO
      values were very high when samples were positive, making even visual
      interpretation possible. We conclude that this new combination assay is an
      excellent screening method for detection of antibodies to the human retroviruses,
      and may be particularly useful for screening blood for transfusion and in
      epidemiological investigations.

PMID- 1357084
TI  - Drug washout issues in studies of cerebral metabolism by positron emission
      tomography in psychiatric patients.
AB  - Many studies of brain glucose utilization by positron emission tomography attempt
      to describe the modifications of the brain activity during psychiatric diseases.
      A major difficulty in such studies is the necessity to assess patients free of
      pharmacological treatment, in order to relate the measured changes in glucose
      utilization to the pathopsychology, and not to a drug effect. In this paper are
      reviewed the arguments from the literature allowing to estimate the drug washout
      time for considering the patients as drug-free. The review is focussed on the
      known effects of the psychotrops on brain glucose utilization. This time is
      approximately six months for the neuroleptics given orally, one month for
      antidepressants, and five and a half half-lives for benzodiazepines. Alternative
      research strategies for avoiding a long drug washout are mentioned, and ethical
      limitations are considered.

PMID- 1357085
TI  - Quick blots and nonradioactive detection of DNA probes for the identification of
      mosquitoes.
AB  - The quick blot protocol is an improved technique for preparing crude insect
      homogenates for hybridization to nucleic acid probes. Individual insects are
      ground in wells of a microtiter plate and transferred to a dot blot manifold.
      This allows preparation of multiple filters and provides uniformity and an
      orderly arrangement of samples. The high background detection resulting from use
      of crude insect homogenates with nonradioactive detection systems was eliminated
      by incubating quick blot filters in a laundry stain remover containing proteases.
      We used mosquito species-specific DNA probes to demonstrate the effectiveness of
      nonradioactive DNA labeling systems with quick blots.

PMID- 1357086
TI  - Safety of Edhazardia aedis (Microspora: Amblyosporidae) for nontarget aquatic
      organisms.
AB  - The susceptibility of common nontarget aquatic organisms to the microsporidium
      Edhazardia aedis was investigated in the laboratory. Eight predacious species
      along with 9 scavengers and filter feeders were tested. The nontarget organisms
      were not susceptible to infection by E. aedis and there was no appreciable
      mortality. To measure the relative safety of E. aedis to nontarget organisms, a
      simple mathematical expression was employed where risk is defined as the product
      of the probability of exposure and the result of exposure (infection) expressed
      as P(e)P(i). In these laboratory tests, the probability of exposure was fixed at
      1 (maximum challenge) and the probability of infection was determined to be 0.
      Therefore, the risk associated with release of E. aedis into the environment is
      considered to be negligible under these conditions. The true risk for nontarget
      organisms to E. aedis can only be determined by careful evaluation of controlled
      field studies in the natural habitat of the target host.

PMID- 1357087
TI  - Host range of Clostridium bifermentans serovar. malaysia, a mosquitocidal
      anaerobic bacterium.
AB  - Clostridium bifermentans serovar. malaysia (C.b.m.) is toxic to mosquito larvae.
      In this study, we quantified its toxicity to the mosquitoes, Aedes aegypti, Ae.
      albopictus, Ae. caspius, Ae. detritus, Anopheles stephensi, An. gambiae, Culex
      pipiens and Cx. quinquefasciatus. Anopheles larvae are the most susceptible,
      followed by Ae. detritus and Ae. caspius, then Culex and other Aedes larvae.
      According to mosquito species, the LC50 varies from 7 x 10(3) to 1.3 x 10(6)
      cells/ml. Three concentrations (10(7), 10(6) and 10(5) cells/ml) of C.b.m.,
      Bacillus thuringiensis var. israelensis (B.t.i.) and Bacillus sphaericus were
      tested on Ae. aegypti, An. stephensi and Cx. pipiens larvae in order to determine
      the time necessary for each concentration to kill 50 and 90% of the population.
      Ninety percent of the 3 mosquito populations are killed within 4-15 h by the
      C.b.m. concentrations. Whatever the concentrations, C.b.m. kills at least 10
      times less rapidly than B.t.i. but always quicker than B. sphaericus. Bioassays
      of C.b.m. bacterial cells or final whole culture were not toxic to Musca
      domestica and Drosophila melanogaster (Diptera) as well as to Phaedon cochleariae
      (Coleoptera) and Spodoptera littoralis (Lepidoptera).

PMID- 1357088
TI  - Factors influencing the activity of Bacillus thuringiensis var. israelensis
      treatments.
AB  - Environmental factors influence the effectiveness of microbial control agents in
      mosquito control programs. Four of these factors (water temperature, larval
      density, sunlight and the effect of associated filter feeders) were studied with
      Bacillus thuringiensis var. israelensis under laboratory and semifield conditions
      in Europe using different instars of Aedes vexans, Ae. aegypti and Culex pipiens.
      Bioassays conducted at a low temperature (5 degrees C) yielded 10-fold higher
      LC50 and LC90 values compared with those conducted at a high temperature (25
      degrees C). The efficacy of B.t.i. decreased in a linear manner with increasing
      larval density. Sunlight can reduce the effectiveness of B.t.i. by several times.
      Competition in food intake by filter feeding Daphnia resulted in lower mortality
      of mosquito larvae after B.t.i. applications.

PMID- 1357089
TI  - Use of an indigenous fish species, Fundulus zebrinus, in a mosquito abatement
      program: a field comparison with the mosquitofish, Gambusia affinis.
AB  - Studies were conducted relating mosquito production in small ponds to presence or
      absence of larvivorous fishes. Data collected showed that native killifish and
      introduced mosquitofish controlled mosquito larvae at the same level and support
      the use of indigenous fish species in mosquito abatement programs.

PMID- 1357090
TI  - Effectiveness of aerially applied Arosurf MSF in the control of the cattail
      mosquito, Coquillettidia perturbans.
AB  - Arosurf MSF was applied to a Massachusetts cattail marsh at 0.5 gallons/acre
      (4.67 liters/hectare) to prevent emergence of Coquillettidia perturbans. One
      application was made by helicopter and three, later in the season, by fixed-wing
      aircraft. The material appeared to prevent adult emergence for about a week after
      the helicopter application, but due to large inter-trap variances in untreated
      controls the results were not statistically significant. Control was spotty with
      the fixed-wing application. One problem was obtaining good coverage at a site
      with difficult aerial access, the second was the interference to delivery of the
      pupicide as the emergent plant canopy developed later in the season.

PMID- 1357091
TI  - Eastern equine encephalomyelitis virus and Culiseta melanura activity at the
      Patuxent Wildlife Research Center, 1985-90.
AB  - Mosquito population densities, virus isolations and seroconversion in sentinel
      quail were used to monitor eastern equine encephalomyelitis virus (EEE) activity
      at the Patuxent Wildlife Research Center, Laurel, Maryland, from 1985 through
      1990. A dramatic increase in the number of Culiseta melanura collected in 1989,
      as compared with the 3 previous years, was associated with virus isolations from
      this species (5/75 pools; n = 542 mosquitoes) and with seroconversion in sentinel
      quail (4/22 birds positive). This was the first detection of EEE virus activity
      in this area since a 1984 EEE outbreak killed 7 whooping cranes.

PMID- 1357092
TI  - Changes in local mosquito fauna following beaver (Castor canadensis) activity--an
      update.
AB  - Drastic reduction of populations of univoltine temporary pool mosquitoes followed
      impoundment of breeding areas by beavers. Mosquito populations persist at very
      low levels over a 10-year period with no evidence of mosquito development in the
      impoundment.

PMID- 1357093
TI  - Analogues of somatostatin bind selectively to brain somatostatin receptor
      subtypes.
AB  - Somatostatin (SRIF) is a neurotransmitter that produces its multiple effects in
      the CNS through interactions with membrane-bound receptors. Subtypes of SRIF
      receptors are found in the CNS that are distinguished by their sensitivities to
      the cyclic hexapeptide MK-678, such that SRIF1 receptors are sensitive to MK-678
      and SRIF2 receptors are insensitive to MK-678. In the present study, we further
      examined the selectivities of a series of structurally diverse SRIF analogues for
      SRIF receptor subtypes. SRIF receptors were labeled by 125I-Tyr11-SRIF, which has
      indistinguishable affinities for SRIF receptor subtypes. The inhibition by MK-678
      was incomplete, indicating this peptide is highly selective for a subtype of SRIF
      receptor that we have termed the SRIF1 receptor. The binding of 125I-MK-678 to
      SRIF1 receptors was monophasically inhibited by SRIF, the octapeptides (such as
      SMS-201-995), and the hexapeptides (such as MK-678), consistent with the highly
      selective labeling of a subtype of SRIF receptor. In contrast, the smaller CGP
      23996-like analogues did not inhibit 125I-MK-678 binding to SRIF1 receptors. The
      binding of 125I-CGP-23996 to SRIF receptors was inhibited by SRIF and the
      octapeptides with Hill coefficients of less than 1, indicating that 125I-CGP
      23996 labels multiple SRIF receptor subtypes. The hexapeptides and CGP-23996-like
      compounds produced only partial inhibitions of 125I-CGP-23996 binding, which were
      additive, indicating selective interactions of these compounds with the different
      receptor subpopulations labeled by 125I-CGP-23996. 125I-Tyr11-SRIF binding and
      125I-CGP-23996 binding to SRIF receptors were likewise only partially affected by
      100 microM guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), a concentration
      that completely abolishes specific 125I-MK-678 binding to SRIF1 receptors. The
      component of 125I-CGP-23996 labeling that was sensitive to GTP gamma S was also
      MK-678 sensitive. Thus, two subpopulations of SRIF receptors exist in the CNS.
      The SRIF1 receptor is sensitive to cyclic hexapeptides such as MK-678 and to GTP
      gamma S but insensitive to smaller CGP-23996-like compounds. The SRIF2 receptor
      is sensitive to the CGP-23996-like compounds and can be selectively labeled by
      125I-CGP-23996 in the presence of high concentrations of the hexapeptides or GTP
      gamma S because, unlike the SRIF1 receptor, the SRIF2 receptor is insensitive to
      these agents. The SRIF receptor subtype-selective peptide analogues will be
      useful in the future characterization of the functions mediated by SRIF receptor
      subtypes in the CNS.

PMID- 1357094
TI  - Characterization of the 5-hydroxytryptamine receptor modulating the release of 5
      [3H]hydroxytryptamine in slices of the human neocortex.
AB  - In the rat brain, the presynaptic 5-hydroxytryptamine (5-HT) autoreceptors
      located on 5-HT terminals correspond to the 5-HT1B subtype. The presence of a 5
      HT receptor probably located on 5-HT nerve endings and modulating transmitter
      release in the human neocortex has been reported, but its detailed
      pharmacological characterization is not yet available. On the other hand,
      receptor binding and autoradiographic results indicate that the 5-HT1B receptor
      subtype is not present in the human brain. We, therefore, studied the modulation
      of the electrically evoked release of [3H]5-HT by various 5-HT receptor agonists
      and antagonists in preloaded slices of human neocortex obtained from 18 patients
      undergoing neurosurgery. The nonselective 5-HT1A/1B/1D receptor agonist 5
      carboxamidotryptamine produced a potent inhibition (70% at 0.03 microM) of the
      electrically evoked release of [3H]5-HT which was blocked by 5-HT receptor
      antagonists with the following relative order of potency: methiothepin greater
      than metergoline = methysergide greater than propranolol. The selective 5-HT1A
      receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin at 0.1 microM did not
      modify the electrically evoked release of [3H]5-HT. The 5-HT1A/1B receptor
      agonist RU 24969 was 10 times more potent at inhibiting [3H]5-HT overflow in the
      rat frontal cortex than in the human neocortex. The potent 5-HT1B receptor
      antagonist cyanopinodolol did not modify the 5-carboxamidotryptamine-induced
      inhibition of the electrically evoked release of [3H]5-HT in slices of the human
      neocortex, but produced by itself a small inhibition of [3H]5-HT
      overflow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357095
TI  - 5,5'-Dihydroxy-4,4'-bitryptamine: a potentially aberrant, neurotoxic metabolite
      of serotonin.
AB  - Previous investigators have detected unknown oxidized forms of 5
      hydroxytryptamine (5-HT) in the CSF of Alzheimer's disease (AD) patients.
      Furthermore, an unidentified autoxidation product of this neurotransmitter is an
      inhibitor of acetylcholinesterase (AChE), an enzyme compromised in the Alzheimer
      brain. In this study it is demonstrated that the major product of autoxidation of
      5-HT is 5,5'-dihydroxy-4,4'-bitryptamine (DHBT). Central administration of DHBT
      to mice at a dose of 40 micrograms (free base) evokes profound behavioral
      responses, which persist until the animals die (approximately 24 h). One hour
      after central administration of DHBT, the levels of norepinephrine, dopamine, 5
      HT, and acetylcholine and their metabolites in whole brain are greatly elevated.
      Disturbances to the catecholaminergic and serotonergic systems were still evident
      shortly before the death of animals. DHBT is also shown to be a noncompetitive
      inhibitor of AChE in vitro. These observations suggest that if DHBT is formed as
      an aberrant metabolite of 5-HT in the human brain, it could potentially be
      neurotoxic and contribute to the neuronal degeneration and other neurochemical
      and neurobiochemical changes associated with AD or perhaps other
      neurodegenerative diseases.

PMID- 1357096
TI  - Eclosion hormone stimulates cyclic GMP levels in Manduca sexta nervous tissue via
      arachidonic acid metabolism with little or no contribution from the production of
      nitric oxide.
AB  - The neuropeptide eclosion hormone acts directly on the nervous system of the
      tobacco hornworm, Manduca sexta, to trigger ecdysis behavior at the end of each
      molt. Previous studies have shown that the action of eclosion hormone is mediated
      via the intracellular messenger cyclic GMP. In the present study we have
      investigated the mechanisms involved in the eclosion hormone-stimulated increases
      in cyclic GMP. No stimulation of guanylate cyclase was seen in homogenized
      nervous tissue, suggesting that eclosion hormone does not directly stimulate a
      membrane-bound form of guanylate cyclase. Nitric oxide synthase inhibitors, N
      methylarginine and nitroarginine, had no effect on eclosion hormone-stimulated
      cyclic GMP levels. By contrast, 4-bromophenacyl bromide, an inhibitor of
      arachidonic acid release, and nordihydroguaiaretic acid, an inhibitor of
      arachidonic acid metabolism, almost completely abolished the eclosion hormone
      stimulated cyclic GMP increase. We hypothesize that eclosion hormone receptors
      are coupled to a lipase, activation of which causes the release of arachidonic
      acid. Either the arachidonic acid directly stimulates the soluble guanylate
      cyclase or further metabolism of arachidonic acid yields compounds that activate
      guanylate cyclase.

PMID- 1357097
TI  - Activation of protein kinase C by phorbol esters and arachidonic acid required
      for the optimal potentiation of glutamate exocytosis.
AB  - The effects of arachidonic acid and phorbol esters in the Ca(2+)-dependent
      release of glutamate evoked by 4-aminopyridine (4-AP) in rat cerebrocortical
      synaptosomes were studied. In the absence of arachidonic acid, high
      concentrations (500 nM) of 4 beta-phorbol dibutyrate (4 beta-PDBu) were required
      to enhance the release of glutamate. However, in the presence of arachidonic
      acid, low concentrations of 4 beta-PDBu (1-50 nM) were effective in potentiating
      glutamate exocytosis. This potentiation of glutamate release by phorbol esters
      was not observed with the methyl ester of arachidonic acid, which does not
      activate protein kinase C. Moreover, pretreatment of synaptosomes with the
      protein kinase inhibitor staurosporine also prevented the stimulatory effect by
      arachidonic acid and phorbol esters. These results suggest that the activation of
      protein kinase C by both arachidonic acid and phorbol esters may play a role in
      the potentiation of glutamate exocytosis.

PMID- 1357098
TI  - Effect of quinine on autoreceptor-regulated dopamine release in the rat striatum.
AB  - In vivo brain microdialysis was used to examine the role of potassium channel
      activation in dopamine (DA) autoreceptor function in the striatum of freely
      moving rats. Local application of the D2 receptor agonists quinpirole or N-0437
      through the dialysis probe significantly reduced extracellular concentrations of
      DA. Local application of the D2 antagonist (-)-sulpiride produced significant
      increases in DA. Local perfusion with quinine, a K+ channel blocker, completely
      blocked the (-)-sulpiride-induced increases in DA but did not affect the DA
      agonist-induced decreases. (-)-Sulpiride completely blocked the effect of
      quinpirole on DA both in control and in quinine-treated animals. At the highest
      dose used, quinine caused a large transient increase in extracellular DA. Local
      application of tetrodotoxin or infusion of Mg2+ in the absence of Ca2+ did not
      prevent this quinine-induced transient increase in extracellular DA. These
      results demonstrate that DA autoreceptors in the striatum regulate DA release in
      awake, behaving animals. Local application of (-)-sulpiride increases DA levels
      by blocking the tonic activation of autoreceptors by endogenous DA. Quinine
      blocks the neuroleptic-induced increase in DA, perhaps by preventing the K+
      channel opening that would normally accompany endogenous autoreceptor activation.
      The fact that exogenously applied DA receptor agonists can decrease extracellular
      DA levels in the presence of quinine suggests that they may be acting at
      extrasynaptic autoreceptors that are not tonically active in vivo. The effect of
      DA agonists on this site is via a DA receptor because it is blocked by (-)
      sulpiride. However, this receptor does not appear to be coupled to a quinine
      sensitive potassium channel.

PMID- 1357100
TI  - Activation of dopamine D2 receptors linked to voltage-sensitive potassium
      channels reduces forskolin-induced cyclic AMP formation in rat pituitary cells.
AB  - 3,4-Dihydroxyphenylethylamine (dopamine) D2 receptor agonists, including BHT 920
      and bromocriptine, and the potassium channel opener minoxidil share the property
      of hyperpolarizing the plasma membrane by activating voltage-dependent potassium
      channels. These drugs were tested for their ability to inhibit the cyclic AMP
      formation induced by forskolin either in intact or in broken pituitary cells. In
      contrast to bromocriptine, which was active in both experimental systems, BHT 920
      and minoxidil inhibited the forskolin-induced cyclic AMP formation in intact-cell
      but not in broken-cell preparations. The effects of BHT 920 were (a)
      concentration dependent, with a calculated IC50 of 0.7 microM, (b) dopaminergic
      in nature, being specifically antagonized by sulpiride, (c) not additive with
      those induced by minoxidil, and (d) less effective in the presence of potassium
      channel blockers, such as 4-aminopyridine and tetraethylammonium. These data
      indicate that the inhibition of forskolin-induced cyclic AMP formation by BHT 920
      in intact pituitary cells is not a primary consequence of receptor occupation,
      but a late event, possibly related to the opening of voltage-dependent potassium
      channels elicited by this drug through the activation of a subtype of dopamine D2
      receptors uncoupled to adenylyl cyclase.

PMID- 1357099
TI  - Stimulation of delta-opioid receptors reduces the in vivo binding of the
      cholecystokinin (CCK)-B-selective agonist [3H]pBC 264: evidence for a
      physiological regulation of CCKergic systems by endogenous enkephalins.
AB  - Cholecystokinin (CCK) and enkephalins appear to be colocalized in several brain
      structures, and a physiological interaction between these peptides has been
      suggested by a large number of pharmacological studies. In this work we have
      shown, by in vivo binding experiments, that the endogenous enkephalins, protected
      from degrading enzymes by mixed inhibitors such as kelatorphan and N-[(R,S)-2
      benzyl-3-[(S)-2-amino-4-methylthiobutyldithio]-1-oxo pro pyl]- L-phenylalanine
      benzyl ester (RB 101), a systemically active prodrug, modulate CCK release in
      mouse brain, leading to an overall increase in the extracellular levels of CCK.
      This was quantified by measuring the effects of both inhibitors on the in vivo
      binding of [3H]propionyl-Tyr(SO3H)-gNle-mGly-Trp-(N-Me)Nle-Asp-Phe-NH2 ([3H]pBC
      264), a selective and highly potent CCK-B agonist. Thus, intracerebroventricular
      injection of kelatorphan produced a dose-dependent inhibition of the in vivo
      binding of [3H]pBC 264 with a maximal effect (40%) at 50 nmol. A similar response
      was observed after intravenous injection of RB 101 (40 mg/kg). The specific
      binding of [3H]pBC 264 was also inhibited (25%) by intravenous injection of the
      selective delta-opioid agonist H-Tyr-D-Cys(StBu)-Gly-Phe-Leu-Thr(OtBu)-OH (BUBUC;
      2 mg/kg) but not by the mu-agonist H-Tyr-D-Ala-Gly-(N-Me)Phe-Gly-ol (5 mg/kg),
      suggesting a preferential involvement of delta-opioid receptors in the modulation
      of CCK release. This was confirmed by using the selective delta-opioid antagonist
      naltrindole, which prevented the inhibitory effects of BUBUC and of enkephalin
      degrading enzyme inhibitors on [3H]pBC 264 binding.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1357101
TI  - 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid recognizes two N-methyl
      D-aspartate binding sites in rat cerebral cortex membranes.
AB  - Binding of 3-[(+-)-2-carboxypiperazin-4-yl][3H]-propyl-1-phosphonic acid
      ([3H]CPP), a competitive inhibitor of N-methyl-D-aspartate (NMDA), has been
      studied in synaptic plasma membranes from rat cerebral cortex. Computer analysis
      of saturation and homologous displacement isotherms deriving from these plasma
      membranes indicated the existence of two binding sites: a specific, saturable,
      high-affinity binding site with a pKD value of 7.53 +/- 0.03 (29.5 nM) and a
      maximum binding value (Bmax) of 2.25 +/- 0.36 pmol/mg of protein, and a low
      affinity site with a KD of approximately 600 nM and a Bmax of 7.0 pmol/mg of
      protein. It is argued that, in the light of current literature evidence, the low
      affinity binding site may represent an agonist-dependent receptor, linked to
      physiological processes such as neurotransmitter release and channel regulation,
      whereas the high-affinity binding site may be linked to an antagonist-preferred
      receptor, for which no function has yet been reported.

PMID- 1357102
TI  - The effect of cyclohexyladenosine on the periischemic increases of hippocampal
      glutamate and glycine in the rabbit.
AB  - We investigated the ability of N6-cyclohexyladenosine (CHA), a potent and
      selective agonist of the adenosine A1 receptor, to attenuate elevations of levels
      of extracellular hippocampal glutamate and glycine that result from episodes of
      transient global cerebral ischemia (TGCI). A total of 30 New Zealand white
      rabbits were randomly assigned to receive 0 (n = 5), 0.1 (n = 8), 1.0 (n = 6), 10
      (n = 6), or 100 (n = 5) microM CHA. The drug was dissolved in artificial CSF
      (vehicle) and administered via a microdialysis probe placed stereotactically into
      the dorsal hippocampus. A second microdialysis probe placed into the
      contralateral hippocampus of each animal was perfused with vehicle alone. Ten
      minutes of TGCI was induced by neck tourniquet inflation and deliberate
      hypotension from 0 to 10 min. Microdialysis samples were collected as follows:
      every 20 min preischemia (at -80, -60, -40, -20, and 0 min); every 5 min during
      ischemia and in the immediate reperfusion period (at 5, 10, 15, and 20 min); and
      every 20 min for the remainder of the reperfusion period (at 40, 60, and 80 min).
      Samples were then analyzed for their concentration of glutamate and glycine by
      HPLC. Following 10 min of ischemia, glutamate levels increased to a peak of 3.28
      +/- 0.55 times baseline and returned to preischemic levels by 40 min, i.e.,
      during reperfusion. Glycine concentrations increased to 5.41 +/- 0.91 times over
      baseline and remained elevated for the duration of the study.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1357103
TI  - Glucose metabolism assessed with 2-deoxyglucose and the effect of glutamate in
      subdivisions of rat hippocampal slices.
AB  - A new approach to the study of glucose phosphorylation in brain slices is
      described. It is based on timed incubation with nonradioactive 2-deoxyglucose
      (DG), after which the tissue levels of DG and 2-deoxyglucose-6-phosphate (DG6P)
      are measured separately with sensitive enzymatic methods applied to specific
      small subregions. The smallest samples had dry weights of approximately 0.5
      microgram. Direct measurements in different regions of hippocampal slices showed
      that within 6 min after exposure to DG, the ratios of DG to glucose in the tissue
      were almost the same as in the incubation medium, which simplifies the
      calculation of glucose phosphorylation rates and increases their reliability.
      Data are given for ATP, phosphocreatine, sucrose space, and K+ in specific
      subregions of the slices. DG6P accumulation proceeded at a constant rate for at
      least 10 min, even when stimulated by 10 mM glutamate in the medium. The
      calculated control rate of glucose phosphorylation was 2 mmol/kg (dry
      weight)/min. In the presence of 10 mM glutamate it was twice as great. The
      response to 10 mM glutamate of different regions of the slice was not uniform,
      ranging from 164% of control values in the molecular layer of CA1 to 256% in the
      stratum radiatum of CA1. There was a profound fall in phosphocreatine levels
      (75%) in response to 10 mM glutamate despite a 2.4-fold increase in glucose
      phosphorylation. Even in the presence of 1 mM glutamate, the increase in glucose
      phosphorylation (50%) was not great enough to prevent a significant drop in
      phosphocreatine content.

PMID- 1357104
TI  - A granulomatous necrotizing arteritis affecting the peripheral nervous system.

PMID- 1357105
TI  - Abstracts of the 65th Congress of the German Society of Neurology. Saarbrucken,
      Federal Republic of Germany. September 23-26, 1992.

PMID- 1357106
TI  - 2-Chlorodeoxyadenosine: drug development priorities.

PMID- 1357107
TI  - On the bioavailability of oral and subcutaneous 2-chloro-2'-deoxyadenosine in
      humans: alternative routes of administration.
AB  - PURPOSE: The antimetabolite 2-chloro-2'-deoxyadenosine (CdA) is a promising
      alternative to alkylating agents for the treatment of lymphoproliferative
      disorders. Its use, however, is hampered by the need for intravenous (IV)
      administration. The aim of the present study was to determine the bioavailability
      of subcutaneously (SC) and orally administered CdA, and to establish an oral dose
      of CdA that could supersede IV administration. PATIENTS AND METHODS: A previously
      developed high-performance liquid chromatography method was used for the
      determination of plasma CdA concentrations in 13 patients. Ten patients were
      treated on alternate days with 0.14 mg/kg/d CdA as a 2-hour IV infusion or by a
      SC injection. Three of these patients were also given 0.14 mg/kg CdA orally in
      enteric-coated capsules. Ten patients were administered CdA orally that was
      dissolved in phosphate-buffered saline (PBS) after treatment with 20 mg
      omeprazole 1 and 6 hours before the administration of CdA. RESULTS: The
      bioavailability of SC CdA was 102% +/- 28% (mean +/- SD), and the bioavailability
      of CdA administered in enteric-coated capsules was 19%, 24%, and 60%. In the
      three patients who were given 0.14 mg/kg orally dissolved in PBS, the
      bioavailability was 48% +/- 8%, whereas in the seven patients who received 0.28
      mg/kg, the bioavailability was 55% +/- 17%. In the 10 patients who were treated
      with the CdA solution orally, the coefficients of variation of the areas under
      the curve (AUCs) after oral and IV administration were similar. Thus, oral
      administration did not add to the interindividual variability. CONCLUSIONS: We
      conclude that orally administered CdA can supersede IV infusion if the dose is
      doubled. SC administration gives a high peak concentration of short duration with
      an AUC identical to that of IV infusion. Thus, SC injection can also be used as
      an alternative to IV infusion.

PMID- 1357108
TI  - Feasibility of using quinine, a potential multidrug resistance-reversing agent,
      in combination with mitoxantrone and cytarabine for the treatment of acute
      leukemia.
AB  - PURPOSE: We demonstrated previously that sera from quinine-treated patients
      reversed the multidrug resistance (MDR) of a human leukemic cell line. We now
      report a phase I and II clinical study that examined the toxicity of the
      combination of quinine with mitoxantrone and cytarabine (Ara-C). PATIENTS AND
      METHODS: Fifteen adult patients with relapsed or refractory acute leukemia were
      treated with quinine formiate (30 mg/kg/d in continuous intravenous (IV) infusion
      from day 1 through day 5 or 6) associated with Ara-C (1 g/m2 in 3-hour IV
      infusion twice a day for 5 days) and five increasing doses of mitoxantrone (from
      8 mg/m2/d for 4 days to 12 mg/m2/d for 5 days). RESULTS: The main toxicity was
      severe myelosuppression: the mean times to leukocyte recovery (> 500/microL),
      granulocytes recovery (> 500/microL), and platelet count recovery (>
      50,000/microL) were 23 days (range, 17 to 29 days), 30.6 days (range, 17 to 48
      days), and 35.4 days (range, 14 to 75 days), respectively. The nonhematopoietic
      toxicity of this regimen was acceptable. Nausea and vomiting were common, but
      severe mucositis was observed in only two patients. Cardiotoxicity was limited to
      transient episodes of moderate supraventricular tachycardia and a clinically well
      tolerated bradycardia. Tinnitus and vertigo were observed in 10 cases (67%), and
      mild hearing loss and transient increase of serum bilirubin were observed in six
      patients (40%). Total quinine serum levels reached a steady-state concentration
      between 6.4 and 18 mg/L in 24 hours. Complete remission (CR) was achieved in
      eight of 14 (57%) assessable patients, and partial response (PR) was achieved in
      two additional patients (14%). P-glycoprotein expression was detected on blast
      cells from five of 13 studied patients before treatment. A response was observed
      in all P-glycoprotein-positive cases. CONCLUSION: Quinine can be used safely as a
      potential reversing agent of MDR for the treatment of clinically resistant acute
      leukemias.

PMID- 1357109
TI  - High-dose consolidation therapy with autologous stem-cell rescue in stage IV
      breast cancer: follow-up report.
AB  - PURPOSE: Fifty-nine patients with newly diagnosed metastatic breast cancer were
      treated with induction chemotherapy followed by high-dose intensification and
      autologous stem-cell rescue (ASCR) to determine therapeutic efficacy. PATIENTS
      AND METHODS: Induction consisted of cyclophosphamide, doxorubicin, vincristine,
      and methotrexate with leucovorin rescue (LOMAC) in 27 patients, or fluorouracil,
      cisplatin, doxorubicin, and cyclophosphamide (FCAP) in 32 patients.
      Intensification after LOMAC was cyclophosphamide and thiotepa (CyTepa) with ASCR,
      and after FCAP it was cyclophosphamide, thiotepa, and carmustine (BCNU) in all
      but eight patients who received CyTepa. RESULTS: Median survival from study entry
      for the entire group was 13.3 months. Median time to progression from reinfusion
      for the 45 patients who underwent intensification was 7.5 months. After LOMAC and
      intensification, there were 12 complete responses (CR) (nine partial responses
      [PRs] after induction converted to CRs). Responses after FCAP and intensification
      were eight CRs (two PRs after induction converted to CRs). Median time to
      treatment failure from reinfusion was 5.4 months for LOMAC and intensification,
      and was 10.5 months for FCAP and intensification. Median survival from study
      entry was 15.1 months for all 27 LOMAC patients and 9.3 months for all 32 FCAP
      patients. Median time to treatment failure from reinfusion for 11 patients who
      were CRs at intensification has not been reached and is more than 13 months
      compared with a median of 5.5 months for the 23 patients in partial remission at
      intensification. CONCLUSIONS: High-dose intensification therapy has led to
      increased CR rates in metastatic breast cancer. The role of such therapy in the
      treatment of stage IV breast cancer requires further refinement.

PMID- 1357110
TI  - Phase II study and long-term follow-up of patients treated with taxol for
      advanced ovarian adenocarcinoma.
AB  - PURPOSE: Based on the results of our phase I study that demonstrated the
      antitumor activity of taxol in a previously treated patient with ovarian cancer,
      a phase II study was conducted to evaluate the efficacy of taxol in patients with
      metastatic ovarian cancer and to evaluate further the toxicity of taxol in this
      group of patients. PATIENTS AND METHODS: Thirty-four patients with metastatic
      ovarian cancer received taxol (180 to 250 mg/m2) as a 24-hour continuous
      infusion. A premedication regimen was used to reduce the likelihood of an acute
      hypersensitivity reaction. RESULTS: Six of 30 assessable patients demonstrated
      complete responses (one patient) or partial responses (five patients; 20%; 95%
      confidence interval [CI], 6% to 34%; range, 2 to 30 months). Additionally, one
      patient had a less than partial objective response (2 months), and two patients
      had stable disease for 6 and 15 months. Those responders had a median survival of
      27 months, and the nonresponders had a median survival of 6 months (P = .0001).
      Myelosuppression was the most significant toxicity. Other adverse effects
      included alopecia and peripheral neuropathy. CONCLUSION: Taxol has significant
      activity in ovarian cancer and should be studied in combination with other active
      agents earlier in this disease.

PMID- 1357111
TI  - HER-2/neu oncoprotein as a prognostic factor in breast cancer.

PMID- 1357112
TI  - Rapid response of B-cell prolymphocytic leukemia to 2-chlorodeoxyadenosine.

PMID- 1357113
TI  - D1-like and D2-like dopamine receptors synergistically activate rotation and c
      fos expression in the dopamine-depleted striatum in a rat model of Parkinson's
      disease.
AB  - Selective agonists for D1-like and D2-like dopamine receptors can interact
      synergistically to enhance each other's actions on locomotion and behavior in
      experimental animals. Clinically, the combination of the D2 agonist bromocriptine
      with L-dopa (which has pronounced D1 effects) is a highly effective treatment for
      Parkinson's disease. The mechanisms underlying this important receptor
      interaction are poorly understood and are the subject of intense study in vitro.
      In rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal
      pathway, D1-selective (but not D2-selective) dopamine agonists produce a marked
      increase in expression of the immediate-early gene c-fos in the striatum
      ipsilateral to the 6-OHDA lesion. In the experiments reported here, we have used
      this in vivo model to explore the possibility that combinations of D1-selective
      and D2-selective agonists might have effects on c-fos transcription that are
      different from those exhibited by D1 or D2 agonists administered alone. We
      examined the effects of the D1-selective agonist SKF-38393 and the D2-selective
      agonist quinpirole (LY 171555) on the expression of Fos-like protein and c-fos
      mRNA in the caudoputamen and made parallel behavioral observations in the same
      animals. A low dose of SKF-38393 produced little contraversive rotation and
      little induction of Fos-like immunoreactivity in the striatum. A low dose of
      quinpirole elicited contralateral rotation but little or no induction of Fos-like
      immunoreactivity in the caudoputamen; there was, however, induction of Fos in the
      globus pallidus ipsilateral to the 6-OHDA lesion. Combination of the low dose of
      SKF-38393 and quinpirole produced a synergistic effect on rotation and elicited,
      in the dopamine-depleted caudoputamen, a striking pattern of Fos-like protein
      expression in which Fos-positive neurons were concentrated in striosomes and in
      the dorsolateral caudoputamen. Northern blot analysis showed that c-fos mRNA was
      expressed following combined agonist treatment but was not detectable after the
      single-agonist treatments. Both the contraversive rotation and the induction of
      Fos-like immunoreactivity were blocked by the preadministration of the D1
      preferring antagonist SCH-23390 and the D2-selective antagonist raclopride in
      combination. Pretreatment with the glutamate NMDA receptor antagonist MK-801 also
      blocked the induction of Fos-like immunoreactivity, and it reversed the rotation.
      These findings suggest a D1/D2 synergistic mechanism that involves the
      participation of D1-responsive striatonigral and D2-responsive striatopallidal
      output pathways, and that is sensitive to glutamatergic modulation.

PMID- 1357114
TI  - GABAergic inhibition of endogenous dopamine release measured in vivo with 11C
      raclopride and positron emission tomography.
AB  - Extensive neuroanatomical, neurophysiological, and behavioral evidence
      demonstrates that GABAergic neurons inhibit endogenous dopamine release in the
      mammalian corpus striatum. Positron emission tomography (PET) studies in adult
      female baboons, using the dopamine D2-specific radiotracer 11C-raclopride, were
      undertaken to assess the utility of this imaging technique for measuring these
      dynamic interactions in vivo. 11C-raclopride binding was imaged prior to and
      following the administration of either gamma-vinyl-GABA (GVG), a specific suicide
      inhibitor of the GABA-catabolizing enzyme GABA transaminase, or lorazepam, a
      clinically prescribed benzodiazepine agonist. Striatal 11C-raclopride binding
      increased following both GVG and lorazepam administration. This increase exceeded
      the test/retest variability of 11C-raclopride binding observed in the same
      animals. These findings confirm that changes in endogenous dopamine
      concentrations resulting from drug-induced potentiation of GABAergic transmission
      can be measured with PET and 11C-raclopride. Finally, this new strategy for
      noninvasively evaluating the functional integrity of neurophysiologically linked
      transmitter systems with PET supports its use as an approach for assessing the
      multiple mechanisms of drug action and their consequences in the human brain.

PMID- 1357115
TI  - Immunogold quantification of glutamate in two types of excitatory synapse with
      different firing patterns.
AB  - A quantitative immunocytochemical method was used to study the regional levels of
      glutamate in two types of lamprey (Ichtyomyzon unicuspis) axon, which both
      activate excitatory amino acid receptors, but which when active exhibit different
      firing patterns. Giant reticulospinal axons fire in brief bursts, while dorsal
      column axons, mainly belonging to cutaneous afferents, show a sustained firing at
      high frequency. In both types of axon, clusters of synaptic vesicles showed a
      strong accumulation of glutamate immunogold labeling, and the density of gold
      particles correlated strictly with the packing density of synaptic vesicles. The
      most densely packed vesicle areas had a particle density corresponding to a
      concentration of fixed glutamate of about 30 mM in coprocessed glutamate
      conjugates, suggesting an intravesicular glutamate concentration of at least 60
      mM. The level of labeling in axoplasmic matrix was considerably lower, but
      differed significantly between the two types of axon. Dorsal column axons showed
      a particle density in axoplasmic matrix that was approximately four times higher
      than that in giant reticulospinal axons. The mitochondrial glutamate labeling was
      also significantly stronger in the dorsal column axons. In addition, the number
      of mitochondrial profiles surrounding vesicle clusters was about four times
      higher in dorsal column synapses than in reticulospinal synapses. Antisera to
      aspartate, GABA, glutamine, and homocysteate failed to produce a specific
      labeling of synaptic vesicle clusters in reticulospinal or dorsal column axons.
      In conjunction with previous demonstrations of a stimulus-induced vesicle
      depletion in giant reticulospinal synapses (Wickelgren et al., 1985), these
      results imply that glutamate is released from synaptic vesicles. The different
      extravesicular glutamate levels in reticulospinal axons and dorsal column axons
      may relate to different requirements for the refilling of synaptic vesicles in
      these functionally divergent neurons.

PMID- 1357116
TI  - Developmental regulation of leucine-enkephalin expression in adrenal chromaffin
      cells by glucocorticoids and innervation.
AB  - Most catecholaminergic cells derived from the sympathoadrenal lineage of the
      neural crest contain one or more neuropeptides. Although a great deal is known
      about the development and regulation of catecholaminergic properties in these
      cells, relatively little is known about the developmental control of their
      neuropeptidergic properties. We have investigated the possible role of
      glucocorticoids and preganglionic innervation in the regulation of leucine
      enkephalin (L-Enk) expression in cultures of embryonic and neonatal adrenal
      chromaffin cells and in mature chromaffin cells in vivo. Exposure of embryonic
      and neonatal chromaffin cells to the synthetic glucocorticoid dexamethasone
      increases L-Enk content. Neonatal chromaffin cells grown in medium containing
      elevated levels of potassium to mimic depolarization also exhibited increased L
      Enk levels. The depolarization-induced increase in L-Enk was selectively
      inhibited by treatment with the enkephalin analog [D-Ala, d-Leu]-enkephalin to
      mimic the enkephalinergic component of the preganglionic innervation. Denervation
      of the adrenal gland in vivo resulted in a dramatic increase in L-enk expression
      that could be partially mimicked by selectively blocking enkephalinergic
      transmission with administration of the opiate receptor antagonist naloxone.
      Taken together with the developmental time course and pattern of L-Enk expression
      in vivo, our results suggest that glucocorticoids and the preganglionic
      innervation regulate the developmental expression of this peptide in adrenal
      chromaffin cells and therefore participate in the generation of the mature
      neurochemical phenotypes present in the adrenal medulla. Further, in adult
      chromaffin cells similar factors appear to regulate the expression of L-Enk,
      which could in turn participate in physiological responses to stress.

PMID- 1357117
TI  - Neurochemical afferents controlling the activity of serotonergic neurons in the
      dorsal raphe nucleus: microiontophoretic studies in the awake cat.
AB  - Serotonergic (5-HT) neurons of the brainstem dorsal raphe nucleus (DRN) have been
      implicated in a diversity of physiological and behavioral processes in
      vertebrates. However, despite extensive information about the intrinsic
      properties and the efferent projections of this neurochemical system, little
      information is available regarding the afferents that control its activity. This
      study investigated the neurotransmitters that regulate the activity of DRN-5-HT
      neurons under physiologically relevant conditions, by utilizing
      microiontophoresis in combination with single-unit recordings in the awake, head
      restrained cat. This made it possible to examine the direct effects of
      neurotransmitters on DRN-5-HT neuronal activity, and, through the use of specific
      antagonists, to study the roles of these neurotransmitter inputs during
      physiological conditions that influence DRN-5-HT neuronal activity. The results
      indicate that (1) iontophoretic application of the GABA antagonist bicuculline
      reversed the typical suppression of neuronal activity seen during slow wave
      sleep, but had no effect on maintained activity during wakefulness. The
      suppression of neuronal activity during REM sleep was generally unaffected by
      application of bicuculline. This suggests a role for a GABAergic input to DRN-5
      HT neurons in controlling some aspects of their state-dependent activity. (2)
      Iontophoretic application of the excitatory amino acid (EAA) antagonist kynurenic
      acid reduced the magnitude of the neuronal response evoked by phasic auditory
      stimuli, but had no effect on the spontaneous activity of these neurons,
      suggesting a role for an EAA input to the DRN in mediating the response to phasic
      sensory stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357119
TI  - [Effects of anti-PAF agents on nasal response after allergen challenge in guinea
      pigs].
AB  - We previously reported that Platelet-activating factor (PAF) activities were
      detected in nasal lavage fluids from patients with allergic rhinitis and in
      ovalbumin (OA) sensitized guinea pigs after topical allergen challenge. In guinea
      pigs, a topical application of PAF produced an increase in nasal vascular
      permeability which was inhibited by a PAF-antagonist (CV3988). To define the role
      of PAF in allergic rhinitis, we examined the effects of anti-PAF agents (WEB2086)
      and anti-allergic agents (Azelastine) on nasal airway resistance (NAR) and nasal
      symptoms in actively sensitized guinea pigs. Guinea pigs (200-300g) were
      sensitized by intraperitoneal injection of OA (10 micrograms/kg) and alum
      (5mg/kg) three times at two week intervals and repeated inhalation of OA
      (1mg/min., for 3 minutes) everyday for four weeks. The NAR was measured serially
      for 6 hours by an apparatus using the oscillation method. NAR change was
      expressed as a percent ratio to the pre-challenge value. Nasal symptoms were
      evaluated by counting the number of sneezing discharges and scratching movements
      for 30 minutes. The anti-PAF agent or Azelastine were administered orally at 2-3
      hours before the topical allergen challenge. We noted a biphasic increase in NAR
      after allergen challenge. The increase in NAR during early phase was not affected
      but that during late phase was significantly inhibited by the anti-PAF agent and
      Azelastine. The nasal symptoms were inhibited by WEB2086 and Azelastine. Our
      results suggest that PAF activities might play an important role in late phase
      NAR increase following allergen challenge.

PMID- 1357118
TI  - Structural determinants of barium permeation and rectification in non-NMDA
      glutamate receptor channels.
AB  - A single site in recombinant glutamate receptor channels of the GluR1-GluR4
      family has been previously identified as a key regulator of ion permeation. The
      natural amino acid at this position (arginine in GluR2 but glutamine in GluR1,
      GluR3, and GluR4) determines both the ability to pass outward current and the
      divalent cation permeability of kainate-activated receptor channels. By
      mutagenesis of GluR6, we demonstrated that the same site also controls the
      ability to pass outward current in another non-NMDA receptor family. Additional
      mutations at and near this site in GluR3 indicated that the position of the
      arginine is critical to function, that the ability to pass outward current is not
      necessarily linked to low barium permeability, and that the size as well as the
      charge of the side chain at this position influences barium permeation. These
      results provide evidence that this site forms part of the selectivity filter of
      glutamate receptor channels.

PMID- 1357120
TI  - Histocompatibility screening by molecular techniques: use of polymerase chain
      reaction products and heteroduplex formation.
AB  - Novel molecular approaches have recently become available allowing improved major
      histocompatibility complex (MHC) matching of potential allogeneic bone marrow
      donors and recipients. Current cellular and serological assays are hindered by
      aberrant cell populations and limited reagents which only detect an individuals'
      phenotype. Therefore, a molecular screening protocol which discriminates at the
      genotypic level would be advantageous. Here we describe a two-step DNA-based
      approach that can be applied to large-scale screening of potential donors. A
      primary screen, utilizing polymerase chain reaction (PCR), reduces the potential
      donor population, whereas a secondary or fine resolution screen uses DNA
      heteroduplex analysis to determine identity or non-identity at specific loci.
      Heteroduplex analysis generates a DNA migration pattern that is unique for
      alleles at a given locus, and is more sensitive than serology in discriminating
      among individuals. Here we demonstrate the potential feasibility of this approach
      by analyzing results at one MHC locus, HLA-DQ. Since this method does not rely on
      typing sera or viable lymphocytes, it is not subject to the variability found in
      the traditional methods. In contrast to traditional methods, these molecular
      techniques can provide the critical information needed to select a potential bone
      marrow donor.

PMID- 1357121
TI  - A sensitive method for the detection of poly-A tails of mRNA using a biotin
      labelled heteropolymer of dT:rA.
AB  - We have developed a highly sensitive non-radioactive in situ hybridization
      technique that enables us to study the production of mRNAs in tissues. As part of
      the validation procedure of our methods, we examined various methods of detecting
      poly-A RNA tails of mRNA. We have used three types of biotin-labelled probes
      complementary to poly-A sequences: a 25-mer poly-dT oligonucleotide, a polymer of
      dT, and a heteropolymer of dT:rA. All the probes had the same specificity of
      reactivity but the heteropolymer of dT:rA gave the strongest signals as
      visualized histochemically by the use of alkaline phosphatase as the detection
      enzyme. All the probes tested for poly-A detection showed reactivity. The poly-dT
      oligonucleotide showed a strength of signal comparable to published results. The
      biotinylated polymer of dT gave a stronger signal than that of the
      oligonucleotide, and the heteropolymer was the strongest of all. The strong
      signal seen with the heteropolymer probe is due to probe complexing during
      hybridization, in which additional binding between sense and antisense strands of
      the probe (i.e. poly-rA and poly-dT) amplifies the number of biotin molecules at
      the hybridization site; this strategy has been exploited by us as a means of
      visualizing low copy numbers of specific mRNAs.

PMID- 1357122
TI  - Assessment of rejection in orthotopic human heart transplantation using
      proliferating cell nuclear antigen (PCNA) as an index of cell proliferation.
AB  - Myocardial biopsies taken during the management of cardiac transplantation were
      stained for proliferating cell nuclear antigen (PCNA). Counts of PCNA-positive
      interstitial cells were compared, in retrospect, with the reported histological
      grade of rejection. Biopsies without rejection had negligible numbers of PCNA
      positive cells. Ascending grades of rejection were paralleled by an increase in
      the number of PCNA-positive cells [grade 1, 13 +/- 35 (mean +/- SD); grade 2a, 38
      +/- 40; grade 2b, 91 +/- 75; grade 3, 170 +/- 78]. While highly significant, in
      statistical terms, the overlap in the counts between different grades means that
      prediction of rejection from the PCNA count alone is not feasible. Biopsies
      graded as 0 or 1 and which immediately preceded more severe rejection episodes
      showed no increase in PCNA-positive cells. The majority of PCNA-positive cells
      are fibroblasts, although in grade 2b and 3 rejection a small population of PCNA
      positive T lymphocytes occurs. PCNA staining is also seen in cardiac myocytes
      immediately after transplantation, during rejection episodes, and late after
      transplantation in the absence of rejection. The positive PCNA staining of
      cardiac myocytes probably reflects DNA synthesis that occurs with the shift
      toward polyploidy in hypertrophy.

PMID- 1357123
TI  - Correction of antigen-specific T-lymphocyte function by recombinant cytokines in
      children infected with human immunodeficiency virus type 1.
AB  - To determine the role of cytokines in the immunodeficiency of children infected
      with human immunodeficiency virus type 1 (HIV-1), we compared the antigen
      specific (tetanus toxoid-induced) T-lymphocyte blastogenesis of HIV-1-infected
      patients with and without the addition of exogenous interleukin-1 and interleukin
      2. Acquisition of in vitro antigen-specific immunologic function was seen in some
      patients after the addition of exogenous cytokines. The antigen-specific
      immunodeficiency in some HIV-1-infected children is due to defects in cytokine
      production rather than to an absence of antigen-specific T lymphocytes.

PMID- 1357124
TI  - Phase I study of continuous-infusion soluble CD4 as a single agent and in
      combination with oral dideoxyinosine therapy in children with symptomatic human
      immunodeficiency virus infection.
AB  - To determine the safety and pharmacokinetics of recombinant soluble CD4 (sCD4)
      administered by continuous intravenous infusion to children with symptomatic
      human immunodeficiency virus type 1 infection, we conducted a phase I study at
      the National Cancer Institute. Three dose levels of sCD4 were evaluated: 100,
      300, and 1000 micrograms/kg per day. After an initial 12 weeks of treatment with
      sCD4 alone, dideoxyinosine at a dose of 90 mg/m2 every 8 hours was added and
      subjects were observed for an additional 12 weeks. Combination therapy was
      continued in patients in whom it was well tolerated. In addition to toxicity and
      pharmacokinetic monitoring, surrogate markers of antiviral activity were
      evaluated. Eleven children were enrolled in the study. During the 12 weeks of
      treatment with sCD4 alone, and during subsequent sCD4 plus dideoxyinosine
      combination therapy, no significant toxic reaction attributable to sCD4 or
      dideoxyinosine was encountered. Low-level anti-CD4 antibodies developed in two
      patients. Steady-state sCD4 levels increased proportionately at higher doses. The
      CD4 cell counts and serum p24 antigen levels did not provide evidence of
      antiviral activity. We conclude that sCD4 was well tolerated at doses up to 1000
      micrograms/kg per day when administered by continuous intravenous infusion;
      however, evidence of in vivo antiviral activity was not observed in this study.

PMID- 1357125
TI  - Comparative effects of atrial natriuretic peptide and E. coli heat-stable toxin
      on rat intestinal transport.
AB  - Conflicting data have been published in favor of or against a secretory effect of
      atrial natriuretic peptide (ANP) in the intestine. The reported effects resemble
      that of Escherichia coli heat-stable enterotoxin (ST). In this work the effects
      of ANP were studied in well established experimental systems and compared with
      that of ST. Both peptides induced a prompt secretion of water, Na, and Cl with no
      effects on K net transport in the in vivo rat perfused jejunum. The addition of
      ST, but not of ANP, evoked an increase of short circuit current in rat intestinal
      mucosa mounted in Ussing chambers. ST induced a significant increase in guanylate
      cyclase activity in intestinal homogenates, whereas ANP showed no effect. No
      binding sites for ANP were detected in basolateral or brush border membranes, nor
      in isolated enterocytes by a suction filtration technique. In conclusion, ANP
      acts as a short-lived intestinal secretagogue in the rat. Its mechanism of action
      is different from that of E. coli ST and appears to be indirect, since is not
      mediated by specific intestinal receptors and is not evident in vitro.

PMID- 1357126
TI  - Measurement of colonic tissue cyclosporine concentration in children with severe
      ulcerative colitis.
AB  - Recent studies suggest that cyclosporine may be an alternative to colectomy in
      children with severe ulcerative colitis who fail traditional therapy with bowel
      rest and high-dose corticosteroids. We report the clinical course of two such
      children. Patient 1 received oral cyclosporine at 15 mg/kg/day for 1 week
      followed by 8 mg/kg/day for 6 weeks. Clinical remission occurred within 5 days
      and has been sustained for 24 weeks after azathioprine was substituted for
      cyclosporine. Patient 2 received oral cyclosporine at 7-8 mg/kg/day for 7 days
      after which colectomy was performed due to lack of clinical improvement. Blood
      cyclosporine levels for patient 1 ranged from 95 to 406 ng/ml and for patient 2
      from 36 to 65 ng/ml. Sigmoid colonic tissue cyclosporine concentrations for
      patients 1 and 2 were 10,058 and 3,205 ng/g, respectively. The patient who
      responded had significantly higher blood and colonic tissue cyclosporine
      concentrations than the patient who did not respond. Further studies with larger
      numbers of patients are needed to determine if there is a correlation between
      blood and colonic tissue cyclosporine concentrations and clinical response.

PMID- 1357127
TI  - Inhibition of adhesion of S-fimbriated Escherichia coli to epithelial cells by
      meconium and feces of breast-fed and formula-fed newborns: mucins are the major
      inhibitory component.
AB  - We investigated the ability of meconium, feces from human milk-fed (HMF)
      newborns, and feces from formula-fed (FF) newborns to inhibit adhesion of S
      fimbriated E. coli to human buccal epithelial cells. S-fimbriae are a common
      property of E. coli strains causing sepsis and meningitis in neonates. Meconium
      had the highest content of neuraminic acid and the strongest inhibitory effect on
      bacterial adhesion. HMF also exerted high inhibitory activity while FF was
      markedly less active: To achieve inhibitory effects comparable to HMF a sixfold
      amount of FF was required. Glycoproteins from excretions were separated by gel
      chromatography. Fractions obtained were analyzed for adhesion-inhibiting
      activity. In all excretions analyzed, the mucin-containing fraction could be
      identified as the major inhibitory component. Inhibition was probably mediated by
      specific interaction of this fraction with S-fimbriae, as shown by binding of
      isolated fimbriae on Western blots after electrophoretic separation of
      glycoproteins. In conclusion, our data support the view that the mucin-containing
      fraction from meconium and human milk exerts antibacterial functions by
      preventing adhesin-mediated binding of pathogenic bacteria to mucosal epithelia.

PMID- 1357128
TI  - Pancreatoduodenectomy with preservation of the stomach and pylorus: a safe and
      effective alternative in children.
AB  - The time-honored surgical approach to resectable tumors of the head of the
      pancreas or distal common bile duct has been a Whipple operation for adults and
      children. In recent years, pylorus-preserving pancreatoduodenectomy has been used
      for adults. The postoperative physiological advantages may be enhanced in
      children, and for this reason the pylorus-sparing approach was used in a 15-year
      old girl with a tumor of the distal common duct. The pylorus-preserving
      pancreatoduodenectomy was safe and effective in this patient and should be
      considered for children with resectable tumors of the distal common bile duct and
      pancreatic head.

PMID- 1357129
TI  - [Drug reactions and interactions].

PMID- 1357131
TI  - Hydrolysis kinetics of phospholipids in thermally stressed intravenous lipid
      emulsion formulations.
AB  - A model 20% w/v emulsion, prepared with either a commercially available
      pharmaceutical grade soy oil or a highly purified grade of oil from the same
      origin and stabilized with a commercially available mixture of egg yolk
      phospholipids was passed through a Microfluidics homogenizer until the mean
      particle size fell below 500 nm diameter. Samples stored in sealed all-glass
      ampoules were thermally stressed over a temperature range of 5-90 degrees C and
      samples taken at appropriate intervals for analysis by HPLC. Hydrolysis
      degradation kinetics were in conformation with the Arrhenius equation. The energy
      of activation for phosphatidylcholine was virtually identical for emulsions
      prepared with either pharmaceutical or purified oil (65 and 63 kJ mol-1,
      respectively). For phosphatidylethanolamine itself the respective activation
      energies were 53 and 54 kJ mol-1, suggesting that the source of the oil used in
      preparing the emulsions had no significance in the degradation processes of the
      resulting systems.

PMID- 1357130
TI  - Pharmacology of nebivolol.
AB  - Nebivolol is a mixture of equal amounts of two enantiomers: SR3-nebivolol (d
      nebivolol) and RS3-nebivolol (l-nebivolol). SR3-nebivolol is a potent and
      selective beta 1-adrenergic antagonist both in vitro and in vivo. Nebivolol
      acutely lowers blood pressure in spontaneously hypertensive rats and induces a
      slight decrease in total peripheral vascular resistance and a slight increase in
      cardiac output in anaesthetised dogs. These hemodynamics effects cannot be
      explained by beta 1-adrenergic antagonism and are largely attributable to RS3
      nebivolol.

PMID- 1357132
TI  - Epi-fluorescence microscopy and image analysis used to measure diffusion
      coefficients in gel systems.
AB  - A method using epi-fluorescence microscopy and image analysis has been developed
      to follow and quantify the diffusion of fluorescent compounds through gels. Two
      mathematical approaches were employed to calculate diffusion coefficients. The
      spatial resolution provided by the fluorescence microscope allowed diffusion to
      be followed over very short distances; accordingly diffusion coefficients were
      obtained within minutes, even for slowly diffusing systems. The method was
      successfully applied to the diffusion of macromolecules into agar, carbopol and
      mucus gel systems.

PMID- 1357133
TI  - Improvement of large intestinal absorption of insulin by chemical modification
      with palmitic acid in rats.
AB  - The intestinal absorption of 125I-labelled palmitoyl insulin was examined
      following administration into in-situ closed large intestinal loops of rats. When
      mono- and dipalmitoyl insulins (Palins-1 and Palins-2, respectively) were
      administered in polyoxyethylene hydrogenated castor oil (HCO 60) micellar system
      into intestinal loops, a marked increase in plasma radioactivity and a
      corresponding disappearance of residual radioactivity in the intestinal lumen
      were observed in the following rank order: Palins-2 greater than Palins-1 greater
      than native insulin. In addition, the derivatives were more stable than native
      insulin in the mucosal tissue homogenates of the large intestine. These results
      suggest that chemical modification of insulin with palmitic acid may not only
      increase the lipophilicity of insulin but also reduce its degradation, resulting
      in the increased transfer of insulin across the large intestinal mucous membrane.
      The linoleic acid-HCO 60 mixed micelles system did not have a significant effect
      on the large intestinal absorption of radioactivity associated with the
      lipophilic insulin analogues.

PMID- 1357134
TI  - Effect of oily vehicles on absorption of mepitiostane by the lymphatic system in
      rats.
AB  - [14C]Mepitiostane in various vehicles was administered to the small intestine of
      anaesthetized rats with cannulated thoracic ducts, and the effect of lipids on
      lymphatic absorption was examined. The extent of lymphatic absorption was
      greatest when administered in triolein and sesame oil, which are triglycerides of
      long-chain fatty acids. Absorption in the presence of other vehicles was in the
      order of 10% Tween 80 aqueous solution greater than monolein greater than oleic
      acid approximately oleic acid/monolein (2:1 mol/mol) greater than aqueous
      suspension. Differences between the extents of lymphatic absorption of
      mepitiostane in the various formulations were not due to variation in the lymph
      flow but to the increased secretion of chylomicron and very low density
      lipoproteins. During absorption of mepitiostane from the small intestine, oil
      affected not only the penetration into epithelium cells and the metabolism in
      them, but also the partition between blood and lymph.

PMID- 1357135
TI  - Effect of bile on absorption of mepitiostane by the lymphatic system in rats.
AB  - The effects of bile and site of gastrointestinal absorption on the lymphatic
      absorption of the highly lipophilic drug, mepitiostane were examined using
      thoracic duct-cannulated rats. The lymphatic absorption from the small intestine
      was very small in the absence of bile compared with that when bile was present.
      The lymphatic absorption was greatest when drug was administered to the upper
      small intestine with bile, was smaller for the lower regions of the small
      intestine, and was negligible for the stomach and the large intestine. A
      correlation was observed between the extent of lymphatic absorption and the
      secretion of chylomicron and very low density lipoproteins after administration
      to various regions with or without bile. The portal absorption data of
      mepitiostane confirmed that site specificity occurs in the partition of drug
      between blood and lymph.

PMID- 1357136
TI  - Effects of salicylate and other enhancers on rectal absorption of erythropoietin
      in rats.
AB  - To develop a new treatment for patients with anaemia in which erythropoietin
      (EPO) can be given without injection, the effects of promoters of the rectal
      absorption of EPO were studied. Recombinant human (rHu) EPO (5000 units) in a
      dosing solution or in a rectal suppository was placed in the rectum of healthy
      rats and changes in serum EPO levels were monitored by an enzyme-linked
      immunosorbent assay. Without a promoter, rHuEPO was not absorbed. Sodium
      glycocholate, sodium caprate, and sodium salicylate in the solution of rHuEPO
      increased the absorption of rHuEPO. Sodium salicylate or sodium caprate in the
      suppository with rHuEPO also increased its absorption. The bioavailability of
      rHuEPO in a suppository containing 5% sodium salicylate compared with that by an
      intravenous injection was 1.2%. rHuEPO given in rectal suppositories containing
      sodium salicylate and inserted once a day for 6 consecutive days increased
      erythropoiesis in peripheral blood.

PMID- 1357137
TI  - Interaction between cicletanine and the eicosanoid system in human subcutaneous
      resistance arteries.
AB  - In human subcutaneous resistance arteries in-vitro, the relaxation produced by
      the novel furopyridine compound cicletanine (30 microMs) was inhibited by 51% (P
      less than 0.0001) in the presence of 20 microMs of the cyclo-oxygenase inhibitor
      indomethacin. Maximal cicletanine-induced relaxation was reduced by both the
      cyclo-oxygenase inhibitor mefenamic acid and the relatively specific blocker of
      prostacyclin synthetase, tranylcypromine by 55% (P less than 0.0005) and 43% (P
      less than 0.01), respectively. The potassium channel blocker, glibenclamide (100
      microMs), did not affect the relaxation produced by cicletanine but did inhibit
      the relaxation produced by the potassium channel blocker cromakalim (P less than
      0.0001). Cromakalim-induced relaxation was inhibited in the presence of
      indomethacin; relaxation induced by cromakalim (30 microMs) was reduced by 22% (P
      less than 0.02). The relaxation produced by the hypotensive agonists sodium
      nitroprusside, hydrochlorothiazide, bumetanide and nicardipine was unaffected by
      incubation with indomethacin. The results suggest that the vascular eicosanoid
      system, specifically prostacyclin, may be involved in the mechanism of the acute
      vasodilator action of cicletanine. Although at high doses, cicletanine is a
      diuretic, in this model it did not act like either a thiazide or a loop diuretic.
      The acute vasodilator action of the thiazide diuretic, hydrochlorothiazide was a
      novel finding of this study. Cromakalim showed a reduced response in the presence
      of indomethacin suggesting an involvement of the eicosanoid system in its
      mechanism of action.

PMID- 1357138
TI  - Tetrandrine and isotetrandrine, two bisbenzyltetrahydroisoquinoline alkaloids
      from Menispermaceae, with rat uterine smooth muscle relaxant activity.
AB  - The effects of two bisbenzyltetrahydroisoquinoline alkaloids, 1S,1'S tetrandrine
      and its isomer 1R,1'S isotetrandrine, were investigated in rat isolated uterus in
      order to identify the mechanism of relaxant action and to study the influence of
      the absolute configuration on the activity of these alkaloids. Both inhibited the
      uterine contraction induced by high K+, acetylcholine and oxytocin. In Ca(2+)
      free medium, isotetrandrine relaxed the sustained contraction induced by oxytocin
      but tetrandrine did not. The relaxant effects of the alkaloids may be due to
      blockade of calcium influx through specific channels. Tetrandrine and
      isotetrandrine modify the calcium channel in a nonreversible manner whilst only
      isotetrandrine acts intracellularly. Tetrandrine shows a more specific relaxant
      activity as a calcium entry blocker.

PMID- 1357140
TI  - Design, synthesis and biological activity of a series of torasemide derivatives,
      potent blockers of the Na+ 2Cl- K+ co-transporter: in-vitro study.
AB  - Pharmacomodulation of the torasemide molecule, a loop diuretic inhibiting Na+ 2Cl
      K+ co-transport in the thick ascending limb of the loop of Henle has been
      performed in order to obtain new long-acting diuretics. The aim of this study was
      to decrease the metabolism of the drug and to slow down its rate of excretion by
      increasing its hydrophobicity. The present study describes the synthesis and the
      inhibitory potency of new torasemide derivatives in the bioassay system of the
      cortical thick ascending limb of rabbit. A correlation between the lipophilicity
      (log P') of these substances and their activity as inhibitors of the Na+ Cl- K+
      co-transporter was observed. The present design led to compounds more active than
      torasemide. Structure-activity relationships permit us to propose an interaction
      model between torasemide derivatives and the Na+ 2Cl- K+ co-transport system of
      the cortical thick ascending limb.

PMID- 1357139
TI  - In-vivo blood-brain barrier transport of a novel adrenocorticotropic hormone
      analogue, ebiratide, demonstrated by brain microdialysis and capillary depletion
      methods.
AB  - The transport of ebiratide, a novel adrenocorticotropic hormone (ACTH) analogue,
      [H-Met-(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], through the blood-brain barrier
      was directly demonstrated in-vivo. [125I]Ebiratide (16.9 MBq mL-1) or
      [14C]sucrose (29.2 MBq mL-1) known to be restrictively transported through the
      blood-brain barrier was infused into the rat internal carotid artery at a flow
      rate of 50 microL min-1 for 10 min, and after 15 min infusion the distribution
      volume of each compound in the brain parenchyma was determined by the capillary
      depletion method. The distribution volume of [125I]ebiratide was 167.8 +/- 62.2
      microL (g brain)-1, which was about seven times higher than that of [14C]sucrose
      (24.9 +/- 4.0 microL g brain)-1, indicating the uptake of ebiratide into brain
      parenchymal cells. During the infusion into the internal carotid artery, brain
      microdialysis was simultaneously performed to directly collect the brain
      interstitial fluid as the dialysate. Radioactivity was detected in the dialysate
      during the [125I]ebiratide infusion and HPLC analysis of the dialysate revealed
      that the intact ebiratide accounted for greater than or equal to 80% total
      radioactivity. The concentrations of [125I]ebiratide and [14C]sucrose in the
      brain interstitial fluid were estimated based on the relative recovery obtained
      in the in-vitro recovery study. The brain interstitial fluid/internal carotid
      arterial blood concentration ratio for [125I]ebiratide was determined to be 1.47
      x 10(-2) +/- 0.17 x 10(-2) and was about eight times higher than that for
      [14C]sucrose (1.92 x 10(-3) +/- 0.36 x 10(-3)), indicating significant transport
      of ebiratide to the brain interstitial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357141
TI  - Interspecies differences and scaling for the pharmacokinetics of xanthine
      derivatives.
AB  - Pharmacokinetic characteristics of the new xanthine bronchodilators, enprofylline
      and 1-methyl-3-propylxanthine (MPX), were investigated in mice, rats, guinea
      pigs, rabbits and dogs. The possibility of an interspecies pharmacokinetic scale
      was also evaluated. The concentration of these two drugs in plasma and urine was
      determined by HPLC. Pharmacokinetic parameters were calculated using model
      independent methods. The disappearance curves of the two drugs from plasma varied
      markedly among animal species. Interspecies differences in the plasma protein
      binding of each drug were observed for all animals in the study. Differences in
      the biotransformation of enprofylline and MPX were also confirmed among the
      various animal species: enprofylline is mainly excreted in an unchanged form in
      urine while MPX follows a non-renal route of elimination. In all animals, the
      renal clearance for enprofylline was greater than the glomerular filtration rate,
      indicating active tubular secretion. Significant allometric relationships were
      seen between the values of total body clearance and steady state volume of
      distribution for both total and unbound enprofylline and species body weight, but
      similar correlations could not be recognized for MPX. Renal clearance of
      enprofylline was also closely correlated with species body weight, suggesting no
      interspecies difference with relation to affinity and/or capacity for the active
      tubular secretion mechanism of enprofylline. Our findings suggest that xanthine
      derivatives, including enprofylline, are mainly eliminated via the kidney, and an
      estimate of the basic pharmacokinetics in man can be obtained from data in
      experimental animals.

PMID- 1357142
TI  - Enhancement of the stability of thrombin by polyols: microcalorimetric studies.
AB  - Glycerol increased the transition temperature (Tm) of thrombin in a concentration
      dependent fashion up to a concentration of 50% glycerol in aqueous buffer
      solution. Glycerol showed a comparable effect on Tm of trypsin. This effect on Tm
      of thrombin was not seen in the presence of excess sodium chloride (1.2 M) in
      aqueous buffer solution. The stabilizing effect of glycerol may be due to
      increased energy demand to unfold the protein molecule, as reflected by an
      increase in Tm. This stabilizing effect, as measured by Tm, was seen for other
      polyols, including sucrose, and was also dependent on the concentration of the
      stabilizing agent. Microcalorimetry may be used as an effective tool to screen
      for the protective action of compounds in enzyme stabilization studies before
      conducting the time-consuming and expensive stability studies of proteins in the
      presence of additives under different storage conditions.

PMID- 1357143
TI  - Failure of tetrodotoxin to inhibit the prostaglandin-induced secretory response
      of rat small intestine in-vitro.
AB  - Tetrodotoxin (TTX, 10 microM) did not inhibit prostaglandin E2 (PGE2)-stimulated
      increases in electrical activity in intact or stripped sheets of rat small
      intestine, although it reduced basal electrical activity in the intact
      preparation. Basal and PGE2-stimulated cAMP production by enterocytes isolated
      from the small intestine was unaffected by TTX. Thus its reported ability to
      inhibit prostaglandin-induced fluid secretion in-vivo does not appear to
      represent a direct interaction of the neurotoxin with the mechanism of
      prostaglandin action at the enterocyte.

PMID- 1357144
TI  - The effect of temperature and pH on the deacetylation of diamorphine in aqueous
      solution and in human plasma.
AB  - The effect of temperature on the kinetics of the deacetylation of diamorphine and
      6-monoacetylmorphine was studied in human plasma. Diamorphine was rapidly and
      quantitatively degraded to 6-monoacetylmorphine with initial half-lives of 354,
      18 and 3 min at temperatures of 4, 25 and 37 degrees C, respectively. Further
      deacetylation to morphine was not detected. In aqueous solution, diamorphine was
      quantitatively degraded to give 6-monoacetylmorphine as the major product and
      morphine as a minor product, the rate of deacetylation being dependent on
      temperature and pH. At pH 4.0 and 5.6 diamorphine had a half-life of greater than
      14 days at all temperatures but at alkaline pH diamorphine was rapidly
      deacetylated. The rate of deacetylation of 6-monoacetylmorphine was consistently
      slower than that of diamorphine under identical conditions of pH and temperature.
      A method is described for the rapid stabilization and subsequent assay of
      diamorphine in plasma which will prevent errors in estimation of the drug due to
      unwanted hydrolysis.

PMID- 1357145
TI  - Effect of exogenous copper on lipid peroxidation in rat hepatocytes. Possible
      involvement of protein kinase C.
AB  - We have investigated the direct effect of copper on malondialdehyde formation in
      rat isolated hepatocytes. Copper was found to decrease the cell viability with
      concomitant production of malondialdehyde in a time related manner. In addition
      the protein kinase C activator, PMA, was found to have a synergistic effect with
      copper on rat hepatocytes. These results indicate that protein kinase C may be
      important in mediating hepatotoxicity after exposure to copper.

PMID- 1357146
TI  - Induction of propranolol metabolism in the Hep G2 human hepatoma cell line.
AB  - Metabolism of propranolol by the human hepatoma cell line Hep G2 was studied.
      Although metabolism qualitatively was similar to that in-vivo, the P450-mediated
      N-desisopropylation clearly predominated. Pretreatment of cells with 3
      methylcholanthrene increased the activity of this pathway 14-fold, whereas
      phenobarbitone had no effect. This is similar to the pathway-selective inductive
      response observed for cigarette smoking in-vivo. As in-vivo, secondary metabolism
      of N-desisopropylpropranolol was extensive. This could, however, be completely
      blocked by 0.1 microM clorgyline, a potent MAO type A inhibitor. As in human
      liver microsomes, the stereochemistry of propranolol metabolism demonstrated a
      preference for the R(+)-enantiomer. These observations emphasize the usefulness
      of the Hep G2 cell line as a model of man.

PMID- 1357147
TI  - Atrial natriuretic peptide inhibits the spontaneous contractions of rabbit
      isolated ileum.
AB  - The present study investigates the effects of atriopeptin II on spontaneous
      phasic contractions of rabbit isolated ileum. Atriopeptin II caused a significant
      and concentration-dependent decrease in ileum motor activity. This effect was
      mimicked by 8-Br-cGMP and it was not affected by pretreatment with tetrodotoxin.
      Verapamil significantly decreased ileum contractions; however, in the presence of
      this calcium blocker, atriopeptin II further reduced ileal motility. These
      findings demonstrate that atriopeptin II depresses the motility of rabbit ileum
      through a cGMP-dependent mechanism and suggest that neither ileal neural networks
      nor extracellular calcium are involved in this effect.

PMID- 1357148
TI  - The pharmacokinetics of oral itraconazole in AIDS patients.
AB  - To test the hypothesis that absorption of orally administered itraconazole may be
      reduced in patients with the Acquired Immunodeficiency Syndrome (AIDS), 8
      patients with AIDS were given two 100 mg capsules of itraconazole for 15 days.
      Plasma levels were measured by HPLC hourly for the first 8 h following ingestion,
      then at 24, 48, 72 and 96 h on days 1, 8 and 15. Peak plasma levels occurred
      after approximately 4 h. Mean peak plasma concentrations were 446 +/- 196 and 530
      +/- 214 ng mL-1 at days 8 and 15. The area under the curve over 24 h (AUC0-24)
      was 2105 +/- 1241, 7679 +/- 3838 and 8748 +/- 4385 ng mL-1 h for days 1, 8 and
      15, respectively. Steady-state was achieved after one week of dosing. There was
      no evidence of hepatotoxicity and one patient stopped itraconazole due to a rash.
      It may be concluded that the absorption of oral itraconazole capsules is reduced
      in AIDS patients, by a factor of approximately 50%, when compared with normal
      volunteers. AIDS patients may require higher doses of itraconazole than used in
      non-AIDS patients to achieve comparable plasma levels.

PMID- 1357149
TI  - Disposition of asarone after intravenous administration to rabbits assessed using
      HPLC.
AB  - A simple and sensitive high-performance liquid chromatography (HPLC) method for
      the determination of asarone in rabbit plasma has been developed. Up to 0.1 mL of
      plasma containing asarone was deproteinated by acetonitrile, which contained an
      internal standard (indomethacin). The supernatant was injected into a Nucleosil
      7C18 column using acetonitrile-water-triethylamine (55:45:0.1 v/v, pH 5.4-5.5,
      adjusted with orthophosphoric acid) as the mobile phase and UV detection at 257
      nm, followed by UV spectrum identification (between 200 and 380 nm) with a
      photodiode array detector. The method is rapid, easily reproduced, selective and
      sensitive. It was applied to pharmacokinetic studies of asarone in rabbit, after
      5, 10, or 20 mg kg-1 intravenous administration. Rapid distribution followed by a
      slower elimination phase was observed from the plasma concentration-time curve.
      The plasma disposition at each dose fitted well to a two-compartment open model
      and the terminal disposition became much slower as the dose was increased,
      suggesting a nonlinear dose-dependent plasma asarone disposition.

PMID- 1357150
TI  - An in-vitro comparison of controlled release aminophylline tablets: Phyllocontin
      Continus and Pecram.
AB  - It has been suggested that two controlled release preparations containing
      aminophylline, Phyllocontin Continus and Pecram, are clinically equivalent and
      are therefore interchangeable. In this study, an in-vitro evaluation of the two
      preparations was completed using the British Pharmacopoeia dissolution apparatus,
      initially using water and then an acid/buffer medium to provide a similar pH
      environment to that within the gastrointestinal tract. Similar release profiles
      were found when water was used as the dissolution medium, with very little
      variation between tablets within each group. Good fits were obtained for
      dissolution-controlled release and diffusion-controlled release models. When the
      acid/buffer solution was used as the dissolution medium a reduction in the rate
      of release was observed with Phyllocontin. It was predicted that if this was
      repeated in-vivo then differences in the peak plasma levels between the two
      formulations would be seen, although these may be masked by the other variables
      encountered.

PMID- 1357151
TI  - Risk of developing cytomegalovirus retinitis in persons infected with the human
      immunodeficiency virus.
AB  - This study examines the risk of developing cytomegalovirus (CMV) retinitis as a
      function of the duration and degree of CD4+ lymphocyte depletion. A retrospective
      analysis of 135 persons infected with the human immunodeficiency virus (HIV) was
      performed. Kaplan-Meier estimates for the percentage of patients developing CMV
      retinitis during the 27-month study period were calculated. Twenty-six patients
      were diagnosed as having CMV retinitis. In 14 of these patients, T cell
      phenotyping was done within the 3 months preceding diagnosis. The mean CD4+
      lymphocyte count for these patients was 15.6 cells/mm3 (range, 2-33/mm3). At 27
      months, the percentage of patients developing CMV retinitis with baseline CD4+
      lymphocyte counts of 0-50, 51-100, and 101-250 cells/mm3 was 41.9%, 26.3%, and
      14.7%, respectively (log-rank test, p = 0.003). The odds ratio for developing CMV
      retinitis for those with baseline CD4+ lymphocyte counts of 0-50 cells/mm3
      compared with those with CD4+ lymphocyte counts of 101-250 cells/mm3 was 4.62 (p
      = 0.002). Twenty-four patients had CD4+ lymphocyte counts of < or = 50 cells/mm3
      for an average of 13.1 months prior to diagnosis. Twenty-two patients had an
      acquired immune deficiency syndrome (AIDS)-defining illness diagnosed for an
      average of 18.0 months prior to the onset of retinitis. CMV retinitis is most
      likely to develop in patients with AIDS when the CD4+ lymphocyte count is < or =
      50 cells/mm3.

PMID- 1357152
TI  - Randomized, placebo-controlled, double-blind study of low-dose oral interferon
      alpha in HIV-1 antibody positive patients.
AB  - One hundred forty-nine patients of private physicians in Toronto, Canada, who
      were positive for human immunodeficiency virus (HIV), medically stable, and had
      CD4 cell counts of < 700 cells/mm3 participated in a randomized, double-blind
      trial of placebo versus low-dose (50 U) versus high-dose (100 U) oral interferon
      alpha. Treatment allocation was balanced according to baseline CD4 cell count and
      history of prior antiviral therapy. Patients were observed at 4 and 8 weeks for
      assessment of adverse events and several measures of disease status, including
      CD4 cell count, beta 2-microglobulin, weight, and Karnofsky score. We detected
      neither short-term benefits nor adverse effects from oral interferon-alpha
      therapy.

PMID- 1357153
TI  - Nutritional status and food intake in human immunodeficiency virus infection.
      GI/HIV Study Group.
AB  - Nutritional status and food intake of HIV+ and HIV- homosexual men that were free
      from enteric pathogens were compared. Food intake (7-day weighed record),
      anthropometry, and D-xylose excretion were measured in 44 patients (9 HIV-, 35
      HIV+). HIV+ patients were found to be thinner, based on anthropometric
      measurements of skinfold thickness (p < 0.05) and percentage body fat (p < 0.05),
      and they also tended to be lighter than the HIV- patients. No differences were
      observed in the arm muscle mass or the food intake of the two groups. In the HIV+
      patients, regression analysis was used to correlate changes in nutritional status
      with progression of the disease, using CD4+ lymphocyte count as a measure of
      severity. A decrease in CD4 count positively correlated with a decrease in weight
      (r = 0.48, p < 0.01), body mass index (r = 0.41, p < 0.05), and arm muscle area
      (r = 0.42, p < 0.01). Energy intake (r = 0.67, p < 0.01), serum albumin (r =
      0.52, p < 0.01), and D-xylose excretion (r = 0.57, p < 0.0001) also positively
      correlated with CD4 count. Multiple regression analysis revealed a relationship
      between CD4 count, weight, and energy intake, indicating that as the disease
      progresses, a decline in weight is seen parallel to a reduction in food intake.
      These data indicate that changes in body composition and nutritional status are
      present throughout the stages of HIV disease, though no causal relationships can
      be interpreted from this study. The initial changes appear to be due to loss of
      fat stores, as determined by anthropometry.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357154
TI  - Characterization of polymorphs and solvates of 3-amino-1-(m
      trifluoromethylphenyl)-6-methyl-1H-pyridazin-4-one.
AB  - The characterization of two polymorphs of the title compound (F2692; 1) by
      differential scanning calorimetry (DSC), microanalysis, proton nuclear magnetic
      resonance spectroscopy, thermogravimetry, thermomicroscopy, infrared
      spectroscopy, and X-ray diffractometry is described. Both polymorphs are
      crystalline, with form II being more stable at temperatures less than 160 degrees
      C. The thermal behavior was studied at different rates of heating, and the
      enthalpies of transition were calculated from DSC data. The transformation of
      aqueous suspensions of form I to the water-stable form II is described, and the
      heats of solution and intrinsic aqueous dissolution rates of both polymorphs were
      determined. 1 also formed solvates with dimethyl sulfoxide and 1-methyl-2
      pyrrolidinone. The solvates were studied by thermogravimetry, DSC, and infrared
      spectroscopy.

PMID- 1357155
TI  - Nicotinic receptor-evoked release of acetylcholine and somatostatin in the
      myenteric plexus is coupled to calcium influx via N-type calcium channels.
AB  - Entry of extracellular calcium (Ca++) via voltage-gated Ca++ channels is
      essential for neurotransmitter release. In this study, we examined whether
      nicotinic receptor-stimulated release of acetylcholine (ACh) and somatostatin
      (S14) are coupled to calcium influx via distinct calcium channel subtypes in the
      myenteric plexus. Isolated ganglia from the guinea pig ileal myenteric plexus
      were prepared and placed in perfusion chambers under standard conditions. The
      ganglionic agonist dimethylphenylpiperazinium (DMPP, 10(-6) to 10(-3) M)
      stimulated the release of [3H]ACh in a concentration-dependent manner. This
      release was blocked by hexamethonium or Ca(++)-free medium containing 1 mM EGTA
      and was antagonized by omega-conotoxin, a preferential N calcium channel blocker,
      but was not affected by nifedipine (L channel antagonist) or nickel (T calcium
      channel antagonist). DMPP-evoked release of somatostatin was also antagonized by
      omega-conotoxin, but was not affected by nifedipine or nickel. These observations
      indicate that neurosecretion of ACh and S14 evoked by DMPP is mediated by calcium
      entry via voltage-sensitive N-type Ca++ channels. To provide additional evidence
      that nicotinic receptor stimulation is associated with Ca++ entry via the N-type
      Ca++ channels, we examined the intracellular calcium [Ca++]i concentration of the
      myenteric plexus neurons using fura-2 microspectrofluorometry. Basal [Ca++]i of
      single ileal myenteric neurons was 65 +/- 5 nM. Perfusion with DMPP (10(-6) to
      10(-3) M) caused a rapid, transient elevation in [Ca++]i which was abolished by
      Ca(++)-free medium containing 1 mM EGTA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357156
TI  - Characterization of [3H]YM617, R-(-)-5-[2-[[2[ethoxyring(n)-3H](o
      ethoxyphenoxy)ethyl]amino]- propyl]-2-methoxybenzenesulfonamide HCl, a potent and
      selective alpha-1 adrenoceptor radioligand.
AB  - The binding properties of a new radioligand, R(-)-5-[2-[[2[ethoxyring(n)-3H](o-
      ethoxyphenoxy)ethyl]amino]propyl]-2-methoxybenzenesulfonamide++ + HCl
      ([3H]YM617), were studied in membranes of the rat hippocampus and spleen.
      [3H]YM617 rapidly associated with its binding sites in both membranes and reached
      steady state by 20 min at 25 degrees C. The specific binding of [3H]YM617
      appeared to be saturable, and Scatchard analysis revealed a linear plot,
      suggesting a single population of binding sites with a dissociation constant of
      0.170 +/- 0.016 nM (n = 6) in the hippocampus and 0.195 +/- 0.036 (n = 4) in the
      spleen. The maximal binding sites in the hippocampus and spleen were 203.0 +/-
      43.2 (n = 6) and 72.4 +/- 17.0 (n = 4) fmol/mg protein, respectively.
      Chlorethylclonidine (10(-5) M for 10 min) treatment reduced the Bmax values of
      [3H]YM617 and [3H]prazosin to a similar degree in the rat hippocampus (10-15%)
      and spleen (40-50%). Alpha adrenoceptor agonists and antagonists competed with
      [3H]YM617 for binding sites in the following order: YM617 > prazosin > WB4101 >
      bunazosin > 5-methylurapidil > S(+)-isomer of YM617 > phentolamine > yohimbine >
      norepinephrine = phenylephrine > methoxamine in the hippocampus, and prazosin >
      YM617 > bunazosin > WB4101 > 5-methylurapidil > phentolamine > S(+)-isomer of
      YM617 > yohimbine > norepinephrine > phenylephrine > methoxamine in the spleen.
      In the hippocampus, prazosin and bunazosin produced biphasic displacement of
      [3H]YM617, but not [3H]prazosin binding. In contrast, only monophasic curves were
      obtained against either radioligand in the spleen.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1357157
TI  - Evidence that S-nitrosothiols are responsible for the smooth muscle relaxing
      activity of the bovine retractor penis inhibitory factor.
AB  - Inhibitory factor (IF), an extract of the bovine retractor penis muscle, when
      treated with acid, becomes a vasodilator with properties similar to endothelium
      derived relaxing factor (EDRF). EDRF has been proposed to be nitric oxide (NO),
      long known to be a potent vasodilator. Recently, biologically active IF was
      proposed to be NO, as well, generated by acid activation of inorganic nitrite. We
      compared acid-activated IF with acid-activated nitrite and found that NO
      formation was not sufficient to explain the properties of acid-activated IF.
      Endothelium-denuded rings of rabbit aorta were used to test the smooth muscle
      relaxing properties of IF and nitrite. Although both IF (0.5 ml) and nitrite (1
      microM) relaxed phenylephrine-contracted rabbit aorta to a similar extent after
      acid activation (approximately 30%), several significant differences were
      observed. IF was most active when acid activated by a 5-min, pH 2 step followed
      by neutralization; nitrite was relatively inactive when acid activated in this
      manner, and was most active when assayed immediately after acidification to pH 2.
      Purging with argon for 5 min reduced the smooth muscle-relaxing activity of 1.0
      microM nitrite from 27 +/- 2 to 10 +/- 2% relaxation, whereas the activity of IF
      was not changed by argon purging (control, 31 +/- 2% relaxation; argon purged, 34
      +/- 2% relaxation). When IF samples were assayed for nitrite content, the amount
      of nitrite found (0.5-5 nmol/0.5 ml sample) was not sufficient to explained the
      observed smooth muscle relaxing activity. Furthermore, acid-activated IF
      significantly stimulated cyclic GMP production by platelet-soluble guanylate
      cyclase from 3.2 +/- 0.2 to 12.4 +/- 0.4 pmol/min/mg protein.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1357158
TI  - Tolerance and cross-tolerance to the activating effects of 3,4
      methylenedioxymethamphetamine and a 5-hydroxytryptamine1B agonist.
AB  - Previous studies indicate that 3,4-methylenedioxymethamphetamine (MDMA) produces
      locomotor hyperactivity in rats by increasing the presynaptic release of
      serotonin (5-HT). Interactions between MDMA and 5-HT receptor antagonists suggest
      that the activating effects of MDMA are mediated via 5-HT1-like receptors. In
      order to assess the contribution of particular 5-HT receptor subtypes to the
      behavioral effects of MDMA, the present studies examined the development of
      tolerance and cross-tolerance to the behavioral effects of MDMA and selective 5
      HT receptor agonists. In the first study, rats were pretreated with saline, a 5
      HT1A receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 1.0 mg/kg), a 5
      HT1B receptor agonist [5-methoyx-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole
      butane dioate (RU24969), 2.5 mg/kg] or a 5-HT1C/5-HT2 receptor agonist (2,5
      dimethoxy-4-iodoamphetamine, 1.0 mg/kg) twice daily for 3 days. The behavioral
      response to S-MDMA (3.0 mg/kg) was assessed 36 hr after the last pretreatment
      injection. Pretreatment with RU24969 antagonized the activating effects of S
      MDMA. In contrast, pretreatment with 2,5-dimethoxy-4-iodoamphetamine did not
      alter the response to S-MDMA, and pretreatment with 8-hydroxy-2-(di-n
      propylamino)tetralin reduced the activity of both control and S-MDMA-treated
      animals. In the second study, rats were pretreated with saline or RS-MDMA (10
      mg/kg), twice daily for 4 days. The behavioral response to saline, S-MDMA (3.0
      mg/kg), RU24969 (2.5 mg/kg) or S-amphetamine (1.0 mg/kg) was assessed 36 hr after
      the last pretreatment injection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357159
TI  - N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal
      norepinephrine release. III. Changes in the NMDA receptor complex induced by
      their functional cooperation.
AB  - N-methyl-D-aspartic acid (NMDA) and non-NMDA ionotropic receptors mediating
      increase of norepinephrine (NE) release coexist on NE rat hippocampus axon
      terminals. Activation of non-NMDA receptors permits activation of NMDA receptors
      also in presence of Mg++ ions and induces important changes in the NMDA receptor
      recognition site and in its intrinsic ion channel. We have now studied the
      effects of this receptor-receptor interaction on the glycine site of the NMDA
      receptor by using two antagonists, 7-chloro-kynurenic acid and (+-)-3-amino-1
      hydroxy-2-pyrrolidone (HA-966). Both the [3H]NE releases induced from rat
      hippocampus synaptosomes by NMDA (no Mg++ added) and by NMDA+quisqualic acid
      (QA), in the presence of 1.2 mM Mg++, were prevented by 7-chloro-kynurenic acid
      with almost identical potency (IC50 values: 0.19 and 0.39 microM, respectively).
      In contrast, HA-966, up to 1000 microM, was ineffective toward NMDA (no Mg++),
      but it blocked the effect of NMDA + QA in presence of Mg++ (IC50 = 1.1 microM).
      HA-966 also antagonized NMDA + QA in Mg(++)-free medium. Thus coactivation of non
      NMDA and NMDA receptors seems to permit the antagonistic activity of HA-966. In
      the presence of Mg++, L-glutamic acid (L-Glu) enhanced [3H]NE release. The
      sensitivity of the L-Glu effect to various antagonists was similar to that of the
      effect of NMDA + QA, indicating that the NMDA receptor complex activated either
      by NMDA + QA or by the physiological transmitter L-Glu in presence of Mg++ ions
      undergoes dramatic conformational changes at the recognition site, at the ion
      channel as well as at the glycine site.

PMID- 1357160
TI  - The role of adrenergic receptors in the initiation of vomiting and its
      gastrointestinal motor correlates.
AB  - We investigated the role of adrenergic receptors in the mechanisms of initiation
      of vomiting and its gastrointestinal (GI) motor correlates. The effects of
      clonidine, UK-14304, St-91, naphazoline, phenylephrine and isoproterenol were
      examined for their ability to initiate vomiting and its GI motor correlates. Only
      the alpha-2 adrenoceptor agonists UK-14304, clonidine, St-91 and naphazoline
      activated vomiting and its GI motor correlates. Tolerance of vomiting, but not
      its GI motor correlates, readily developed to all alpha-2 adrenergic receptor
      agonists but St-91. The responses to UK-14304 or clonidine were blocked by
      idazoxan, yohimbine, clonidine tolerance or high doses of phenoxybenzamine, but
      not by propranolol or prazosin. The responses to UK-14304 or clonidine were also
      blocked by fentanyl, 1-(1-naphthyl) piperazine, methysergide, SCH 22390 or
      scopolamine, but not by haloperidol, sulpiride, domperidone or naloxone.
      Adrenoceptor antagonists, clonidine tolerance or sympathetic blockade did not
      block vomiting or its GI motor correlates activated by apomorphine, CuSO4 or
      cholecystokinin-octapeptide. We concluded that alpha-2 adrenergic receptors of
      the chemoreceptive trigger zone can initiate vomiting and its GI motor
      correlates, but these receptors do not mediate vomiting induced by another
      chemoreceptive trigger zone stimulant, apomorphine, or stimulation of the GI
      tract using CuSO4. However, 5-hydroxytryptamine-2 serotonergic, muscarinic
      cholinergic and opiate receptors within the central nervous system participate in
      controlling emesis activated by alpha-2 adrenergic agonists. Peripheral
      adrenergic receptors do not mediate the GI motor correlates of vomiting.

PMID- 1357161
TI  - Release of endogenous norepinephrine from rat hypothalamus by stimulation of N
      methyl-D-aspartic acid receptors.
AB  - Release of endogenous dopamine and norepinephrine (NE) from rat hypothalamic
      slices superfused with Mg(++)-free medium in the presence of nomifensine and
      tyrosine was measured by high-performance liquid chromatography coupled to an
      electrochemical detector. Superfusion with L-glutamic acid or N-methyl-D-aspartic
      acid elicited a concentration-dependent release of NE but not of dopamine. The
      release of NE was transient, returning toward basal values despite the continued
      presence of the amino acid. Superfusion with 20 mM K+ caused a release of NE that
      declined at a slower rate. Mg++, DL-2-amino-5-phosphonopentanoic acid and MK-801
      (D-5-methyl-10,11,dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine maleate), but
      not 6-cyano-7-nitroquinoxaline-2,3-dione, inhibited the L-glutamic acid-evoked
      release of NE. The release of NE by L-glutamic acid was virtually abolished by
      tetrodotoxin and by elimination of Ca++ from and inclusion of 2 mM ethylene
      glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid in the superfusion
      medium. Repeated L-glutamic acid applications displayed a decreased response,
      whereas repeated exposure to 20 mM K+ did not. Exposure to L-glutamic acid in the
      absence of Ca++ (plus 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'
      tetraacetic acid) or in the presence of DL-2-amino-5-phosphonopentanoic acid did
      not reduce the effects seen on subsequent exposure to L-glutamic acid. Exposure
      to L-glutamic acid in the absence of Mg++ reduced the effect of a subsequent
      exposure to L-glutamic acid. These observations provide evidence for an indirect
      modulation of rat hypothalamic endogenous NE by the N-methyl-D-aspartate
      receptor.

PMID- 1357162
TI  - Carvedilol, a new vasodilator and beta adrenoceptor antagonist, is an antioxidant
      and free radical scavenger.
AB  - The antioxidant effect of carvedilol, a new vasodilating, beta adrenoceptor
      blocker was studied and compared with five other beta blockers. Carvedilol
      rapidly inhibited Fe(++)-initiated lipid peroxidation, measured as thiobarbituric
      acid reactive substance (TBARS), in rat brain homogenate with an IC50 of 8.1
      microM. Under the same conditions, the IC50 values of atenolol, pindolol
      propranolol, celiprolol and labetalol were over 1.0 mM. Carvedilol protected
      against Fe(++)-induced alpha-tocopherol depletion in rat brain homogenate with an
      IC50 of 17.6 microM; propranolol, celiprolol and labetalol, up to 200 microM, did
      not show any effect. Using dihydroxyfumarate/Fe(++)-ADP as a OH.radical
      generating system and 5,5-dimethyl pyrroline-N-oxide (DMPO) as a trapping agent,
      the characteristic DMPO-OH signals were monitored by electron paramagnetic
      resonance. Carvedilol dose-dependently decreased the intensity of the DMPO-OH
      signal, with an IC50 of 25 microM, whereas propranolol, at 500 microM, and
      U74500A, a 21-aminosteroid, at 100 microM, had no effect. The antioxidant effect
      of carvedilol mainly resides in the carbazole moiety, and the substitution of a
      hydroxyl group at certain positions on the phenyl ring of either carbazole or the
      ortho-substituted phenoxylethylamine part of carvedilol resulted in an increase
      in antioxidant activity. Furthermore, the protective effect of carvedilol analogs
      against OH.-mediated neuronal death positively correlated to their antioxidant
      effect. We conclude that carvedilol is a far more potent antioxidant than other
      commonly used beta blockers. The apparent mechanism of carvedilol's inhibition of
      lipid peroxidation is mainly via scavenging free radicals. This novel property of
      carvedilol may contribute to the known cardioprotective activity of this
      compound.

PMID- 1357164
TI  - Comparison of tensile strength of solder joints by infrared and conventional
      torch technique.
AB  - Fabrication of a fixed partial denture may require a soldering step. This study
      compared soldering by a conventional torch procedure with an infrared soldering
      technique. Comparisons were made for tensile strength, porosity, and time
      efficiency between the two methods. No significant difference was found in
      ultimate tensile strength between the two types of solder joints and the
      nonsoldered control samples. Random samples photographed with a scanning electron
      microscope revealed no difference in joint porosity between the two techniques.
      Torch soldering took consistently less time that infrared soldering.

PMID- 1357165
TI  - The fit of fixed partial dentures joined by infrared soldering.
AB  - This study determined the accuracy of fit of three-unit fixed partial dentures
      joined by an infrared soldering technique compared with one-piece fixed partial
      denture castings and individually cast crowns. Wax patterns of prepared Ivorine
      teeth, maxillary left central incisor and maxillary left canine, were injection
      molded; a plastic rod was used as a pontic. One group of patterns was cast as one
      piece dentures; the other group was sectioned in the connector area, cast
      individually and then joined by infrared soldering. Castings were seated on their
      respective dies, embedded in epoxy resin, and sectioned. Gap distances between
      the casting and the die were measured at specified marginal sites with a profile
      projector. Results showed that the fit of infrared-soldered fixed partial
      dentures was significantly better than that of one-piece castings and was
      comparable with the fit of single crowns. The gap openings measured in all
      castings were within the range of clinical acceptability.

PMID- 1357163
TI  - Calcium current modulation in frog sympathetic neurones: multiple
      neurotransmitters and G proteins.
AB  - 1. Whole-cell calcium currents of bullfrog sympathetic neurones were partially
      inhibited by noradrenaline (NA), chicken-II-luteinizing hormone-releasing hormone
      (LHRH), muscarine, ATP, substance P, or intracellular dialysis with guanosine 5'
      O-(3-thiotriphosphate)(GTP-gamma-S) or aluminium fluoride. These agents had
      similar effects on the activation kinetics of calcium current. 2. The amplitude
      of the LHRH effect varied from cell to cell. This did not correlate with cell
      size or the time of whole-cell dialysis. 3. The response to LHRH desensitized
      rapidly. Desensitization to LHRH did not affect inhibition by NA, ATP or
      substance P. 4. The effects of LHRH and NA were partially additive. 5. Cells
      dialysed with GTP-gamma-S still responded to NA or LHRH. However, NA or LHRH
      inhibited a smaller fraction of the calcium current than usual, and second
      applications of the same transmitter to GTP-gamma-S-dialysed cells were
      ineffective. 6. In GTP-gamma-S-dialysed cells, application of LHRH occluded the
      response to NA, but LHRH was still effective after application of NA. 7. The
      effect of GTP-gamma-S decreased during prolonged dialysis. 8. The effect of NA
      was selectively reduced by intracellular dialysis with the A-protomer of
      pertussis toxin (PTX), or extracellular pretreatment with high concentrations of
      whole PTX at room temperature. These treatments had little or no effect on the
      action of LHRH or ATP. 9. It is concluded that multiple G proteins can produce
      identical changes in calcium channel gating. The adrenergic receptor
      preferentially couples to a PTX-sensitive G protein.

PMID- 1357167
TI  - A screening system for tardive dyskinesia: development and implementation.
AB  - 1. Most diagnosed cases of tardive dyskinesia (TD) are mildly inconvenient to the
      patient, but some can be severe or life-threatening. The primary goal of
      intervention should be early identification of abnormal movements related to TD
      and the prescribing of an appropriate medication regimen. 2. Unless specific
      training occurs and a specific monitoring system is in place, TD movements may be
      missed. However, not all movements are necessarily related to TD. 3. Although
      screening and monitoring are valuable, nothing is more important than prevention.
      New medications must be developed that do not carry the risk of TD, and other
      approaches to treat TD must be developed.

PMID- 1357166
TI  - Ophthalmic medications, glaucoma, and the surgical patient.
AB  - Patients receiving chronic ophthalmic therapy have a potential for respiratory or
      hemodynamic compromise during a surgical procedure requiring general anesthesia.
      During the perioperative phase of preoperative assessment and evaluation,
      pertinent patient information is gathered by asking the right questions and
      understanding the significance of the information gathered. The collected
      information, which is unique to these patients, is essential in facilitating in
      the intraoperative plan of care, thus insuring an uncomplicated, satisfactory,
      and safe immediate postoperative outcome.

PMID- 1357168
TI  - Photoperiodic regulation of glutamatergic stimulation of secretion of luteinizing
      hormone in male Syrian hamsters.
AB  - It has been suggested that changes in endogenous glutamatergic stimulation of
      secretion of luteinizing hormone (LH) induced by photoperiod play a role in
      regulating seasonal cycles of reproductive activity. The aim of this study was to
      test the hypothesis that the glutamatergic control of the secretion of LH in the
      male Syrian hamster is sensitive to photoperiod, by determining whether the
      glutamate agonist N-methyl-D-aspartate (NMDA) could stimulate LH secretion in
      this species and, if so, to determine whether the response varied among animals
      exposed to different daylengths. In the first experiment, adult male hamsters
      were housed in either short day (8 h light: 16 h dark) for 6 weeks to induce
      testicular regression, or long days (16 h light: 8 h dark) to maintain testicular
      function, and the effects of systemic administration of NMDA on serum LH
      concentrations were determined. In the short-day hamsters, all s.c. doses of NMDA
      (25-75 mg kg-1 body weight) produced a robust rise in serum LH concentrations
      within 15 min. In the long-day hamsters, basal LH concentrations were higher than
      in short-day hamsters, but only the highest dose of NMDA produced a significant
      increase in LH concentrations, and the magnitude of this increment was less than
      those observed in short days. In hamsters in long days, the low doses of NMDA
      that did not significantly alter LH concentrations nevertheless significantly
      suppressed serum prolactin concentrations, demonstrating the efficacy of the
      drug. In hamsters in short days, serum prolactin concentrations were at the limit
      of detection of the assay, so no inhibitory effect of NMDA on prolactin secretion
      could be determined on this photoperiod. In the second experiment, the effects of
      a fixed dose of NMDA (50 mg kg-1 body weight) was tested at intervals in hamsters
      exposed to short days for a prolonged period such that their testes initially
      regressed, but then became scotorefractory and testicular recrudescence occurred.
      After 6 and 12 weeks in short days, NMDA stimulated LH secretion. However, after
      24 weeks in short days when testicular recrudescence was complete, the response
      to NMDA was lost. A third experiment determined whether the reduced response to
      NMDA in hamsters on long days relative to those in short days might result from
      higher concentrations of circulating testosterone. Hamsters in long days were
      castrated to remove the influence of gonadal feedback, and the response to NMDA
      tested 3 weeks later when endogenous LH concentrations had risen to levels
      characteristic of the chronically castrated condition.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1357169
TI  - No association between rheumatoid arthritis and insulin dependent diabetes
      mellitus: an epidemiologic and immunogenetic study.
AB  - To acquire more information on the controversial question of a possible
      association between rheumatoid arthritis (RA) and insulin dependent diabetes
      mellitus we searched for insulin dependent diabetes mellitus among patients
      hospitalized due to RA in 2 rheumatism hospitals in Finland. Nine subjects with
      insulin dependent diabetes mellitus were found among an annual number of 1460
      patients admitted to one of the hospitals due to RA. These figures give a
      frequency of insulin dependent diabetes mellitus in patients with RA of 0.6% (95%
      confidence interval 0.2-1.0%), which does not exceed the prevalence of insulin
      dependent diabetes mellitus among the middle aged population of Finland in
      general (0.5-0.6%). Accordingly, no overrepresentation of homozygosity for HLA
      DR4 was found among the total number of 25 patients with RA as well as insulin
      dependent diabetes mellitus, though the opposite might be expected as these
      diseases have a common DR4 association--RA with DR4 and DR1 and insulin dependent
      diabetes mellitus with DR4 and DR3. Instead, an increased frequency of DR1 (p
      less than 0.0002) and the antigen combination DR1/4 (p less than 0.01) was found
      in the subjects with both RA and insulin dependent diabetes mellitus compared
      with the subjects with insulin dependent diabetes mellitus alone.

PMID- 1357170
TI  - Isolated polyarteritis nodosa of the male reproductive system.
AB  - Polyarteritis nodosa (PAN) frequently affects the testis and epididymis. We
      describe a 29-year-old man with isolated PAN of the testis and review reported
      cases of isolated PAN of the testis or epididymis. Our patient underwent
      orchiectomy and at followup 17 months later was without evidence of recurrence or
      development of systemic PAN.

PMID- 1357171
TI  - Necrotizing mesenteric vasculitis after longstanding cutaneous polyarteritis
      nodosa.
AB  - We describe a 21-year-old woman with cutaneous polyarteritis nodosa (PAN) who
      developed necrotizing mesenteric vasculitis 6 years after the onset of skin
      disease. Repeated investigation during that 6-year interval failed to reveal any
      evidence of systemic PAN. We were unable to wean the patient from prednisone or
      completely control her skin disease with topical and systemic therapy, including
      supersaturated potassium iodide, dapsone, azathioprine, methotrexate or
      plasmapheresis before the development of the mesenteric vasculitis, which
      responded to cyclophosphamide and prednisone. Development of visceral vasculitis
      after long-standing cutaneous PAN has very rarely been reported.

PMID- 1357172
TI  - Chronic treatment of mice with low dose anti-CD4 antibody results in a
      substantial antixenoantibody response and does not deplete CD4 T cells.

PMID- 1357173
TI  - History of research into hypertension.

PMID- 1357175
TI  - Diel sugar-feeding and host-seeking rhythms in mosquitoes (Diptera: Culicidae)
      under laboratory conditions.
AB  - Mosquito sugar-feeding and host-seeking rhythms were recorded in the laboratory
      using remote sensors. In all five species studied, the two rhythms were nearly
      synchronous. In Anopheles quadrimaculatus Say, Culex quinquefasciatus Say, and
      Aedes triseriatus (Say), host-seeking activity increased slightly earlier than
      sugar feeding in the evening. The evening sugar-feeding period was longer than
      the evening host-seeking period in Aedes aegypti (L.), but the two periods were
      of similar duration in Aedes albopictus (Skuse). In the morning, the only clear
      difference between the two behaviors occurred in Cx. quinquefasciatus, which had
      a host-seeking peak but lacked a sugar-feeding peak. When exposed concurrently to
      both host and sugar stimuli, sugar feeding practically ceased in Ae. albopictus
      and Ae. aegypti. In the presence of host stimuli, the sugar-feeding rhythms of
      An. quadrimaculatus, Cx. quinquefasciatus, and Ae. triseriatus differed from
      those obtained in the absence of host stimuli by having an earlier onset of
      evening activity, a relatively smaller evening activity peak, and a more
      irregular activity pattern during early scotophase, respectively. We concluded
      that inseminated, nulliparous females have nonspecific appetitive feeding
      periods, and that the order in which sugar and blood are sought largely may be a
      function of factors other than differences in diel rhythms.

PMID- 1357174
TI  - Carboxamide group conformation in the nicotinamide and thiazole-4-carboxamide
      rings: implications for enzyme binding.
AB  - Ab initio computations (RHF/6-31G* parallel 3-21G*) were performed on the
      thiazole-4-carboxamide group found in the antitumor drug tiazofurin and its
      dehydrogenase-binding anabolite thiazole-4-carboxamide adenine dinucleotide
      (TAD). Results indicate that the carboxamide group is constrained in the
      conformation in which the amino group is cis-planar to the ring nitrogen. This
      finding is consistent with carboxamide conformations observed in crystal
      structures of the thiazole nucleosides. In contrast, ab initio computations on
      the nicotinamide and dihydronicotinamide rings found in the cofactors NAD+ and
      NADH indicate two stable conformations for the carboxamide group. This finding
      confirms previous computational studies and is consistent with results from a
      survey of the Cambridge Structural Database. Natural bond orbital analysis
      indicates that the low-energy carboxamide conformers of all three heterocycles
      are stabilized by a combination of electrostatic and charge transfer
      interactions. A survey of the Protein Data Bank indicates that the carboxamide
      group conformation in TAD is constrained to that favored by dehydrogenase-bound
      NAD(P)(H).

PMID- 1357176
TI  - Virus-dependent mortality in Rift Valley fever, eastern equine encephalomyelitis,
      and chikungunya virus-inoculated mosquito (Diptera: Culicidae) larvae.
AB  - The effect of inoculation of mosquito larvae with Rift Valley fever (RVF) virus
      on survival to the adult stage was evaluated in Aedes aegypti (L.), Ae. fowleri
      (Charmoy), Ae. mcintoshi Huang, Ae. taeniorhynchus (Wiedemann), Ae. triseriatus
      (Say), Eretmapodites quinquevittatus Theobald, Anopheles albimanus Wiedemann, and
      Culex pipiens L. Pupation rates were similar for RVF virus-inoculated and diluent
      inoculated larvae of all mosquito species tested except Cx. pipiens. However,
      with the exception of An. albimanus and Ae. triseriatus, virtually all pupae
      derived from RVF virus-inoculated larvae failed to emerge successfully as adults.
      In contrast, both pupation and emergence rates were similar for diluent
      inoculated and either La Crosse or St. Louis encephalitis virus-inoculated larvae
      of Ae. taeniorhynchus. There was also poor survival to the adult stage of Ae.
      taeniorhynchus inoculated with either eastern equine encephalomyelitis (EEE) or
      chikungunya (CHIK) virus. The high mortality rates observed under laboratory
      conditions of pupae derived from larvae inoculated with either RVF, EEE, or CHIK
      virus may be responsible for the lack of laboratory confirmation of vertical
      transmission of these viruses.

PMID- 1357177
TI  - The Appleton International Conference: developing guidelines for decisions to
      forgo life-prolonging medical treatment.

PMID- 1357178
TI  - Phenotype-genotype correlations in X linked retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) represents a group of clinically heterogeneous retinal
      degenerations in which all modes of inheritance have been described. We have
      previously found two different clinical profiles in X linked RP as a function of
      age and mode of onset. The first clinical form has very early onset with severe
      myopia. The second form starts later with night blindness with mild myopia or
      none. At least two genes have been identified in X linked forms, namely RP2
      (linked to DXS7, DXS255, and DXS14) and RP3 (linked to DXS84 and OTC) on the
      short arm of the X chromosome. In order to contribute to phenotype-genotype
      correlations in X linked RP, we tested the hypothesis that the two clinical
      profiles could be accounted for by the two different gene loci. The present study
      provides evidence for linkage of the clinical form with early myopia as the onset
      symptom with the RP2 gene (pairwise linkage to DXS255: Z = 3.13 at theta = 0),
      while the clinical form with later night blindness as the onset symptom is linked
      to the RP3 gene (pairwise linkage to OTC: Z = 4.16 at theta = 0).

PMID- 1357179
TI  - Non-specific X linked mental retardation with aphasia exhibiting genetic linkage
      to chromosomal region Xp11.
AB  - A new type of non-specific X linked mental retardation is described in a three
      generation family. The three affected males had severe mental retardation (IQ 20
      to 30), mutism, growth failure, frequent infections, seizures, and the following
      minor anomalies: brachycephaly, frontal hair whorl, square face, large mouth,
      thick lips, and prognathism. There was not a characteristic facies. Normal
      laboratory studies on the proband included a karyotype with fragile X screening,
      skeletal survey, blood amino acid, urine organic acid, and HGPRT levels. Linkage
      analysis was performed with 10 X chromosome DNA probes of which probe DXS255 at
      chromosomal region Xp11.22 gave a maximal two point lod score of 2.10 if phase
      was inferred and 1.20 if it was not. Crossovers were shown with probes mapping to
      regions Xp22, Xp21, and Xq28. Comparison of these patients with 80 X linked
      causes of mental retardation, including 41 which might be classified as 'non
      specific', showed no other disorders compatible with the phenotypic and linkage
      data.

PMID- 1357180
TI  - Mutation analysis of 184 cystic fibrosis families in Wales.
AB  - We describe a molecular analysis of 184 cystic fibrosis (CF) families in Wales.
      To determine accurate frequency data for the CF mutations in the Welsh
      population, families with at least three Welsh grandparents were strictly
      regarded as Welsh. Of these 74 families, we have identified approximately 90% of
      mutations causing CF, with delta F508 accounting for 71.8% and 621 + 1G greater
      than T 6.7%. We observed a significant difference between the Welsh and Scottish
      frequencies of 621 + 1G greater than T. To allow the rapid and efficient
      screening for the more common mutations we modified a multiplex used by Watson et
      al enabling the detection of delta F508, G551D, and R553X simultaneously with 621
      + 1G greater than T. In parallel to this system we ran the Cellmark Diagnostics
      ARMS multiplex kit, which detects delta F508, 621 + 1G greater than T, G551D, and
      G542X. RFLP analysis of the 184 families shows that the delta F508 chromosomes
      are almost exclusively found on the B haplotype (XV2c 1, KM19 2); the other CF
      mutations have more heterogeneous backgrounds. Strong haplotype correlations
      exist between the markers XV2c, KM19, D9, and G2 and the other CF mutations.
      Haplotype data suggest that there are at least seven mutations that remain to be
      identified in these families.

PMID- 1357182
TI  - Beta 1- and beta 2-adrenoceptors in sheep cardiac ventricular muscle.
AB  - The presence of beta 2-adrenoceptors in the sheep ventricular myocardium was
      assessed by the radioligand binding technique and functional studies. In membrane
      preparations, the competition curve between [3H]-dihydroalprenolol and the
      selective beta 1-antagonist CGP 20712A (0.1 nM-1 mM) was clearly biphasic, and
      revealed the presence of two different binding sites showing an affinity (pKD)
      for CGP 20712A of 9.5 +/- 0.9 and 4.5 +/- 0.4, respectively. The relative
      proportion of beta 1:beta 2 adrenoceptors was about 70:30 in both the right and
      left ventricle. In ventricular trabeculae driven at 1Hz, isoprenaline (1-300 nM)
      caused a dose-dependent increase in the force of contraction, the maximum effect
      being 298 +/- 26 mg, associated with reduction of time to peak tension (t1,
      clinotropic effect) and relaxation time (t2, 298 +/- 26 mg, associated with
      reduction of time to peak tension (t1, clinotropic effect) and relaxation time
      (t2, lusitropic effect). The inotropic dose-response curve for isoprenaline was
      significantly shifted to the right by pretreatment of the preparations with 0.1
      microM CGP 20712A or with the selective beta 2-antagonist ICI 118551 (50 nM). In
      the presence of CGP 20712A (0.1 microM), isoprenaline, up to a concentration of
      10 microM, did not affect either t1 or t2; on the other hand, pretreatment of the
      preparations with ICI 118551 (50 nM) fully antagonized the clinotropic but not
      the lusitropic effect of isoprenaline. In the presence of CGP 20712A procaterol
      (0.01-10 microM), a beta 2-adrenoceptor agonist, induced a positive intropic
      effect which was not associated with any significant modifications in t1 or t2.
      This effect was completely abolished by ICI 118551 (50 nM). The positive
      inotropic action of isoprenaline (1 microM) was associated with a significant
      decrease in action potential duration measured at -60 mV (220 +/- 8 and 193 +/-
      10 ms in the absence and presence of isoprenaline, respectively; P less than
      0.05). In the presence of CGP 20712A (0.1 microM) alone, isoprenaline (1 microM)
      still induced a significant increase in contractility but the action potential
      profile was only slightly affected. The effects of isoprenaline were fully
      antagonized by the simultaneous presence of CGP 20712A and ICI 118551 (10 nM). It
      is concluded that both beta 1- and beta 2-adrenoceptors appear to coexist in
      sheep ventricular myocardium where their stimulation mediates a positive
      inotropic effect. However, their functional role on the relaxation phase of the
      twitch may be different.

PMID- 1357181
TI  - Quantitative analysis of depolarization-induced ATP release from mouse brain
      synaptosomes: external calcium dependent and independent processes.
AB  - We and others have shown previously that ATP is secreted from mouse brain
      synaptosomes following depolarization of the membrane by high [K+]o and the time
      course can be monitored accurately by measuring the light emitted from luciferin
      luciferase included in the reaction medium. In the present work we have evaluated
      the relative importance of [Ca2+]o and membrane potential on the ATP secretion
      process by modelling the time course of ATP release under different conditions.
      After correction of the records for destruction of released ATP by synaptosomal
      ecto-ATPase activity, we found that ATP secretion occurs by an apparent first
      order process. We also established that, in addition to the classical [Ca2+]o
      dependent mode, ATP secretion also occurred in the absence of extracellular
      calcium ([Ca2+]o less than 1 microM). Upon lowering the extracellular Ca2+
      concentration, both the rate and the extent of ATP secretion decreased. To assess
      the contribution of membrane potential to the release rate we measured ATP
      secretion at membrane potentials determined by extracellular [K+]o (or [Rb+]o) as
      defined by the distribution of the carbocyanine dye, diSC3(5). Rate constants
      computed from measured secretion curves revealed that this parameter was
      essentially independent of membrane potential in the absence of [Ca2+]o. Noise
      analysis of the light signal showed that the variance increased upon stimulation
      by high [K+]o, suggesting that both modes of secretion are quantal. Thus, we
      conclude that the rate of ATP secretion from nerve terminals depends upon Ca2+
      entry but not on membrane potential, per se.

PMID- 1357183
TI  - NIH workshop on experimental spinal cord injury: modeling and criteria.

PMID- 1357184
TI  - Contraceptives, fat, vitamins debated at prevention forum.

PMID- 1357185
TI  - Coexistence of cholinergic, catecholaminergic, serotonergic, and glutamatergic
      neurotransmitter markers in mouse clonal hybrid neurons derived from the septal
      region.
AB  - Two clonal immortalized neurons designated SN6.1b and SN6.2a were isolated by
      limiting dilution from a mouse embryonic septal cholinergic neuronal hybrid cell
      line SN6 (Hammond et al., 1986). In the serum-containing medium without extra
      differentiating agents, one-third of SN6.1b cells stably exhibited a morphology
      of differentiated neurons with extensive elaborate neurites, while a majority of
      SN6.2a cells, along with the parent cell line SN6, were round in shape with
      poorly branched short processes. Neurochemical studies showed that both clones
      synthesized choline acetyltransferase (ChAT), dopamine, norepinephrine,
      serotonin, and glutamate. Immunocytochemically, they expressed a number of
      neuronal antigens, such as 200-kDa neurofilament protein, neuron-specific
      enolase, microtubule-associated protein 2, tau protein, tubulin, neural cell
      adhesion molecule, Thy-1.2, saxitoxin-binding sodium channel protein, ChAT,
      tyrosine hydroxylase, serotonin, and glutamate. The coexistence of cholinergic,
      catecholaminergic, serotonergic, and glutamatergic neurotransmitter markers in
      the clonal hybrid septal neurons that express a variety of immunocytochemical
      properties of differentiated neurons suggests that embryonic septal cholinergic
      neurons are potentially multiphenotypic with respect to neurotransmitter
      synthesis.

PMID- 1357186
TI  - Cyclic AMP, but not basic FGF, increases the in vitro survival of mesencephalic
      dopaminergic neurons and protects them from MPP(+)-induced degeneration.
AB  - We studied how stimulation of protein kinase C and cAMP-dependent protein kinases
      affect the development of mesencephalic dopaminergic neurons in primary cell
      cultures derived from fetal rats at embryonic day E14. The effects of compounds
      which activate these second messenger systems were compared to those of basic
      fibroblast growth factor (bFGF) and insulin-like growth factor I (IGF-I). In
      mesencephalic cultures, there was a continuous loss of dopaminergic neurons.
      Despite this decline in cell number, neurotransmitter uptake per neuron increased
      with time, indicating that the surviving dopaminergic neurons continued their
      biochemical differentiation while others degenerated. IGF-I and bFGF did not
      affect the number of dopaminergic neurons. However, dopamine uptake per neuron
      was significantly higher in bFGF and IGF-I treated cultures, suggesting that
      these factors stimulated differentiation. Protein kinase C and cAMP-dependent
      protein kinases were not involved in mediating the effects of bFGF and IGF-I.
      Treatment of cultures with phorbol esters did not affect dopamine uptake, whereas
      elevated levels of intracellular cAMP resulted in an increase in dopamine uptake
      which was additive to that elicited by bFGF or IGF-I. Further analysis revealed
      that exposure of mesencephalic cultures to dibutyryl cAMP (dbcAMP) during the
      first 3 days after plating increased the survival of dopaminergic neurons,
      whereas prolonged treatment attenuated the development of the dopamine uptake
      system. Moreover, cyclic AMP, but not bFGF, was able to prevent the degeneration
      of dopaminergic neurons induced by 1-methyl-4-phenyl-pyridinium ion (MPP+), the
      active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The
      results suggest that increased intracellular levels of cAMP protect dopaminergic
      neurons in situations of stress like the process of dissociation and plating or
      the exposure to neurotoxic compounds. Our results reveal novel possibilities for
      the treatment of Parkinson's disease.

PMID- 1357187
TI  - Characteristics of large neutral amino acid-induced release of preloaded L
      glutamine from rat cerebral capillaries in vitro: effects of ammonia, hepatic
      encephalopathy, and gamma-glutamyl transpeptidase inhibitors.
AB  - The release of newly loaded L-[14C]glutamine (L-Gln) from rat cerebral cortical
      capillaries was stimulated by L-transport system substrates: tryptophan (TRY),
      leucine (leu), and nonlabeled L-Gln, respectively, by 32, 50, and 40% above the
      basal release resulting from superfusion with standard Krebs-Henseliet buffer.
      However, no stimulation was observed upon treatment with D-Gln or L-glutamate (L
      Glu), which are not the L-system substrates, or with ammonium chloride. The
      stimulatory effect of TRY was temperature dependent but sodium independent, and
      was abolished in the presence of a sulfhydryl reagent N-ethylmaleimide (NEM). The
      results support the view that the L-Gln-stimulated uptake of large neutral amino
      acids (LNAA) across the blood-brain barrier involves the L-system mediated Gln
      LNAA exchange. The TRY-stimulated Gln release was enhanced in vitro by
      simultaneous addition of ammonium chloride, and in capillaries derived from rats
      with acute hepatic encephalopathy (HE). These results confirm the role of Gln
      LNAA exchange in the excessive accumulation of LNAA in brain observed in a
      variety of hyperammonemic conditions. Superfusion of L-Gln-loaded capillaries in
      a buffer containing gamma-glutamyl transpeptidase (GGT) inhibitors, serine borate
      (SB) or 6-diazo-5-oxo-L-norleucine (DON), increased the basal L-Gln release and
      made it irresponsive to subsequent treatment with TRY. However, the basal release
      was also increased by superfusion with serine alone or Leu, and this treatment
      abolished the subsequent effect of TRY as well. Moreover, DON stimulated L-Gln
      release from capillaries superfused in a standard way, and the effects of DON and
      TRY were additive. Hence, in the present conditions, SB and DON acted as L-system
      substrates rather than as GGT inhibitors. Taken together, the results do not
      support the concept that GGT mediates the Gln-LNAA exchange.

PMID- 1357188
TI  - Further evidence for the dynamic formation of transmitter quanta at the
      neuromuscular junction.
AB  - Fatt and Katz (Nature 166:597-598, 1950; J Physiol 117:109-128, 1952) attributed
      miniature endplate potentials (MEPPs) to the action of a standard quantity of
      transmitter, the quantum (Del Castillo and Katz, J Physiol 124:560-573, 1954).
      Quantal packets of transmitter were proposed to be preformed (Del Castillo and
      Katz, In CNRS Paris (Ed): "Microphysiologie comparee des elements excitables"
      67:245-258, 1957) and stored in large numbers in the motor nerve terminal.
      Statistical analyses of intervals between MEPPs and numbers of quanta composing
      small endplate potentials indicated that quantal release was a random process and
      that release sites functioned independently of each other. With the discovery of
      synaptic vesicles it was proposed that each contained one quantum of transmitter.
      The quantal-vesicular hypothesis (Del Castillo and Katz, as cited above) fails,
      however, to explain amplitude distributions of MEPPs that are skewed and/or that
      show multiple peaks (Kriebel et al., Brain Res Review 15:167-178, 1990). The drop
      formation process (Shaw, "The Dripping Faucet as a Model Chaotic System," Santa
      Cruz, CA: Aerial Press, Inc., 1984) was shown to generate amplitude classes of
      drops that were similar to classes of MEPPs which suggested that rapid changes in
      quantal size and ratios of skew- to bell-MEPPs could be explained with a simple
      dynamic process which determines quantal size at the moment of release (Kriebel
      et al., as cited above, 1990). Further similarities between miniature endplate
      currents (MEPCs) and the formation of drops are reported here. We found that
      rapid changes in MEPC amplitudes and time courses, which accompany an increase in
      frequency, mimic changes in drop sizes that accompany increases in flow rate.
      MEPC intervals have a minimum and their distributions are comparable to those of
      drop intervals. During an increased rate of transmitter release, MEPP amplitudes
      and intervals were positively correlated. The results suggest that spontaneously
      released transmitter "packets" are formed at the moment of release and that
      transmitter supply to the process that forms packets is continuous.

PMID- 1357189
TI  - Role of vif in replication of human immunodeficiency virus type 1 in CD4+ T
      lymphocytes.
AB  - The viral infectivity factor gene vif of human immunodeficiency virus type 1 has
      been shown to affect the infectivity but not the production of virus particles.
      In this study, the effect of vif in the context of the HXB2 virus on virus
      replication in several CD4+ T-cell lines was investigated. vif was found to be
      required for replication in the CD4+ T-cell lines CEM and H9 as well as in
      peripheral blood T lymphocytes. vif was not required for replication in the
      SupT1, C8166, and Jurkat T-cell lines. The infectivity of vif-defective viruses
      depended on the cell type in which the virus was produced. In CEM cells, vif was
      required for production of virus capable of initiating infection in all cell
      lines studied. vif-defective virus produced by SupT1, C8166, and Jurkat cells and
      the monkey cell line COS-1 could initiate infection in multiple cell lines,
      including CEM and H9. These results suggest that vif can compensate for cellular
      factors required for production of infectious virus particles that are present in
      some cell lines such as SupT1, C8166, and Jurkat but are absent in others such as
      CEM and H9 as well as peripheral blood T lymphocytes. The effect of vif was not
      altered by deletion of the carboxyl terminus of gp41, a proposed target for vif
      (B. Guy, M. Geist, K. Dott, D. Spehner, M.-P. Kieny, and J.-P. Lecocq, J. Virol.
      65:1325-1331, 1991). These studies demonstrate that vif enhances viral
      infectivity during virus production and also suggest that vif is likely to be
      important for natural infections.

PMID- 1357190
TI  - Truncation of the human immunodeficiency virus type 1 transmembrane glycoprotein
      cytoplasmic domain blocks virus infectivity.
AB  - Human immunodeficiency virus type 1 contains a transmembrane glycoprotein with an
      unusually long cytoplasmic domain. To determine the role of this domain in virus
      replication, a series of single nucleotide changes that result in the insertion
      of premature termination codons throughout the cytoplasmic domain has been
      constructed. These mutations delete from 6 to 192 amino acids from the carboxy
      terminus of gp41 and do not affect the amino acid sequence of the regulatory
      proteins encoded by rev and tat. The effects of these mutations on glycoprotein
      biosynthesis and function as well as on virus infectivity have been examined in
      the context of a glycoprotein expression vector and the viral genome. All of the
      mutant glycoproteins were synthesized, processed, and transported to the cell
      surface in a manner similar to that of the wild-type glycoprotein. With the
      exception of mutants that remove the membrane anchor domain, all of the mutant
      glycoproteins retained the ability to cause fusion of CD4-bearing cells. However,
      deletion of more than 19 amino acids from the C terminus of gp41 blocked the
      ability of mutant virions to infect cells. This defect in virus infectivity
      appeared to be due at least in part to a failure of the virus to efficiently
      incorporate the truncated glycoprotein. Similar data were obtained for mutations
      in two different env genes and two different target cell lines. These results
      indicate that the cytoplasmic domain of gp41 plays a critical role during virus
      assembly and entry in the life cycle of human immunodeficiency virus type 1.

PMID- 1357192
TI  - Recognition efficiency of the hepatitis B virus polyadenylation signals is tissue
      specific in transgenic mice.
AB  - The hepatitis B virus genome contains a unique polyadenylation (TATAAA) signal
      which is differentially utilized in the formation of the various hepatitis B
      virus transcripts. A head-to-tail multiple-copy insertion of a viral fragment
      comprising the viral enhancer, the X promoter, the X open reading frame, and the
      viral poly(A) signal in transgenic mice allowed us to monitor tissue-specific
      differences in the expression of transcripts initiating from the X promoter.
      These transcripts are efficiently processed at the first polyadenylation site in
      the liver, while in the kidney, the brain, and the testis, a portion of the
      transcripts covers two copies of the transgene, since only the second
      polyadenylation site is properly recognized. As discussed in this article, this
      observation suggests a tissue-specific distribution of cellular factors involved
      in polyadenylation.

PMID- 1357193
TI  - Two-stage Fowler-Stephens orchiopexy in the management of intra-abdominal testes.
AB  - Of 22 boys with an intra-abdominal testis 8 (12 testes) underwent the 2-stage
      Fowler-Stephens orchiopexy. During stage 1 the testicular artery and internal
      spermatic vein were ligated in situ 2 to 3 cm. superior to the intra-abdominal
      testis. The testicular vessels were transected inferior to the ligatures 6 months
      later and the testis was brought to the scrotum with the standard Fowler-Stephens
      orchiopexy technique. Patient age ranged from 1 to 6 years (mean 3.2 years). At
      followup 11 of 12 testes (92%) are in the scrotum and have a normal consistency
      and size, while 1 (8%) is atrophic. In this preliminary series the 2-stage Fowler
      Stephens orchiopexy has a success rate equal or possibly superior to the standard
      Fowler-Stephens orchiopexy. Whether ultimate testicular function is improved,
      however, remains to be determined.

PMID- 1357191
TI  - The human immunodeficiency virus (HIV) gag gene product p18 is responsible for
      enhanced fusogenicity and host range tropism of the highly cytopathic HIV-1-NDK
      strain.
AB  - Formation of large syncytia and rapid cell killing are characteristics of the
      Zairian human immunodeficiency virus type 1 isolate HIV-1-NDK, which is highly
      cytopathic for CD4+ lymphocytes in comparison with the HIV-1-LAV prototype.
      Chimeric viruses containing different combinations of HIV-1-NDK genetic
      determinants corresponding to the splice donor, the packaging signal, and the
      coding sequence of the p18gag protein together with the HIV-1-NDK EcoRI5278
      XhoI8401 fragment were obtained by polymerase chain reaction-directed
      recombination. Phenotypic analysis of recombinant viruses indicated that 75 amino
      acids from the N-terminal part of HIV-1-NDK p18gag protein together with the HIV
      1-NDK envelope glycoprotein are responsible for enhanced fusogenicity of HIV-1
      NDK in CD4+ lymphocytes as well as for enhanced infectivity of HIV-1-NDK in some
      CD4- cells lines. The HIV-1-NDK splice donor/packaging sequence and the sequence
      encoding the gag protein p25 were not important for the variation observed in HIV
      1 fusogenicity.

PMID- 1357194
TI  - Laparoscopic orchiectomy for unilateral intra-abdominal testis.
AB  - We present 2 cases of laparoscopic removal of a unilateral intra-abdominal
      testis. Removal of a unilateral intra-abdominal testis is indicated in patients
      more than 10 years old because the malignant potential of an intra-abdominal
      testis outweighs any cosmetic benefit of orchiopexy. Laparoscopic orchiectomy is
      a safe and effective surgical procedure for adolescents and adults with this
      disease entity providing outpatient therapy and prompt rehabilitation.

PMID- 1357195
TI  - Expression of SSEA-1 carbohydrate antigen correlates with stage, grade and
      metastatic potential of transitional cell carcinoma of the bladder.
AB  - Expression of stage-specific embryonic antigen-1 (SSEA-1) was
      immunohistochemically analyzed in primary cancerous regions from transitional
      cell carcinoma of the bladder. Lymph node metastasis occurred in 14 (50%) of 28
      patients with high expression of SSEA-1 antigen, but in only one (4%) of 23
      patients with low or no expression. Of 36 invasive bladder carcinoma patients
      with no metastasis at operation, 8 (57%) of 14 with high expression of SSEA-1
      antigen died of cancer or had metastasis, whereas 4 (18%) of 22 with low or no
      expression had progression of the disease. In addition, stage pT3b-4 tumors more
      frequently reacted with SSEA-1 MAb than stage pT1 tumors (p less than 0.01).
      Grade 2 or 3 tumors were also more reactive than grade 1 tumors, which were all
      unreactive except for one (p less than 0.01, respectively). Our data suggest that
      SSEA-1, which is a Le(x) antigen, correlates with stage and grade as well as
      metastatic phenotype of transitional cell carcinoma of the bladder.

PMID- 1357196
TI  - National Cancer Institute making more taxol available for refractory ovarian,
      breast cancers.

PMID- 1357198
TI  - [The 34th Congress of the Japanese Society of Clinical Hematology. Osaka, Japan,
      November 5-7, 1992. Abstracts].

PMID- 1357197
TI  - Effect of alpha 1-adrenoceptor blockade on the left ventricular force-length
      relationship in dogs.
AB  - We used the left ventricular (LV) end-systolic force-diameter (Fes-Des) relation
      to evaluate the effect of an alpha1-adrenoceptor antagonist (bunazosin
      hydrochloride) on the contractility of the beta-blocked left ventricle. Nine
      adult mongrel dogs were instrumented with ultrasonic crystals to measure LV
      diameter and a micromanometer to measure LV pressure. Beta-adrenergic and vagal
      blockade was induced with intravenous propranolol (2 mg/kg) and atropine (0.2
      mg/kg), respectively, and preload was decreased by inferior vena caval occlusion.
      The slope (Ec) and extrapolated diameter intercept (Do) of the LV Fes-Des
      relation were derived from end-systolic data obtained in the control state (after
      beta-blockade) and after bunazosin infusion (1 mg/kg). Ec was used as a new index
      of LV contractility. After bunazosin infusion, the heart rate and Ec were
      decreased by 7 and 22%, respectively, in comparison with the control state,
      whereas Do did not change. These results indicate that alpha1-adrenoceptor
      blockade significantly reduces myocardial contractility in the beta-blocked
      canine heart, perhaps by decreasing the intracellular calcium concentration
      and/or myosin ATPase activity.

PMID- 1357200
TI  - [DNA diagnosis for inherited metabolic disorders].
AB  - Progress in molecular genetics has made it possible to detect the structure of
      cDNA and genomic DNA of enzyme and protein, as well as the mutation in DNA level.
      It also provides a vast amount of new information for diagnosis and treatment,
      and it can actually be used in prenatal diagnosis and carrier screening. There is
      great hope that patients with genetic disorders can be treated by somatic gene
      replacement. We introduced here the methods for detection of unknown mutations of
      inherited metabolic disorders, and screening patients for characterized
      mutations, and the expression analysis of mutant cDNA, as an example of
      phenylketonuria.

PMID- 1357199
TI  - [Glutamic acid as an excitatory neurotransmitter].
AB  - The role of L-glutamic acid (Glu) as an excitatory neurotransmitter is reviewed.
      The idea that Glu is a main excitatory transmitter in the central nervous system
      (CNS) is now well supported by several lines of evidence, including its
      excitatory action, presence in the CNS, release, uptake mechanisms and
      suppression of synaptic transmission by its antagonists. Receptors for Glu are
      classified into ionotropic and metabotropic receptors. The former is further
      classified into non-NMDA and NMDA subgroups. The non-NMDA receptor mediates
      signal transduction between central neurons. Activation of the NMDA receptor
      causes an increase in intracellular calcium concentration in the postsynaptic
      neuron and thereby induces plastic changes such as, memory and learning. The
      function of the metabotropic receptor is yet to be elucidated.

PMID- 1357202
TI  - [Metabolic abnormalities of amino acids in patients with alcoholic liver damage].
AB  - The metabolic abnormality of amino acids in patients with alcoholic liver damage
      is discussed. The abnormalities are variable according to the degree of hepatic
      damage, the amount of alcohol consumption, and the intake of amino acids. In
      general, the plasma concentration of branched-chain amino acids, aromatic amino
      acids and alpha-amino-n-butyric acid increases, whereas that of hydroxy amino
      acids, alanine and proline decreases, in alcoholics with liver damage. Serum
      gamma-glutamyltranspeptidase activity increases with the increase of alcohol
      consumption. This increase is accentuated by lowered carbohydrate intake at the
      time of alcohol ingestion. A nutritional survey among healthy male subjects
      revealed that the intake of cereals decreases with increasing amount of alcohol
      consumption, a finding which suggests that the intake of some amino acids may be
      altered by drinking habit.

PMID- 1357201
TI  - [The metabolic basis of the hyperphenylalaninemias and tyrosinemia].
AB  - The hyperphenylalaninemias are caused by the defect of either phenylalanine
      hydroxylase (PAH) or tetrahydrobiopterin (BH4) cofactor. The former is diagnosed
      as phenylketonuria (PKU) or benign hyperphenylalaninemia, based on the serum
      phenylalanine values. The latter, so called malignant hyperphenylalaninemia,
      includes three enzyme defects, dihydropteridine reductase (DHPR), 6-pyruvoyl
      tetrahydropterin synthase (PT PS) and guanosine triphosphate cyclohydrolase (GTP
      CH). Excess phenylalanine and its metabolites cause brain damage before 6 years
      of age. Deficiency of BH4 impairs two other hydroxylases (tyrosine and
      tryptophan), and severe neurological symptoms develop because of the lack of
      neurotransmitters. Tyrosinemia I, II, and III are different enzyme defects,
      fumarylacetoacetate hydrolyase (FAH), hepatic tyrosine aminotransferase (TAT),
      and 4-hydroxyphenylpyruvate acid oxidase, respectively. Tyrosinemia I is
      associated with severe involvement of the liver, kidney and central nervous
      system. Tyrosinemia II has mental retardation, palmar hyperkeratosis and corneal
      ulcers. Tyrosinemia III has mild mental retardation but no eye or skin
      manifestations.

PMID- 1357203
TI  - [Amino acid metabolism in neurodegenerative diseases].
AB  - Although various neurological diseases occur in patients with inborn error of
      metabolism of amino acids, amino acids also act as neurotransmitters. Glutamic
      acid, aspartic acid and glycine play roles as an excitatory neurotransmitter, but
      exert a neurodegenerative effect in case of the excessive release. Extensive
      studies have recently been performed on glutamate receptors, especially N-methyl
      D-aspartate (NMDA) receptor in the hippocampus. Alzheimer brain shows a decreased
      number of NMDA receptors in the frontal cortex. The parkinsonian changes caused
      by MPTP is abolished by the administration of a NMDA antagonist. gamma
      Aminobutyric acid (GABA) acts as an inhibitory amino acid. The content of GABA is
      low in the striatum of patients with Huntington's disease. The number of NMDA
      receptor is decreased also in Huntington striatum. These observations may give a
      clue for the prevention of various neurodegenerative diseases.

PMID- 1357204
TI  - [Amino acid metabolism in endogenous psychoses: significance of amino acids as
      neurotransmitter, precursor of monoamines and allosteric regulator of neuro
      receptors].
AB  - Amino acid metabolism in endogenous psychoses has been discussed in relation to
      monoamine synthesis. There are no consistent findings which prove altered
      monoamine syntheses to be the primary change. Our finding, which suggests
      decreased amino acid transport across the blood-brain barrier in schizophrenia,
      does not necessarily mean an insufficient amino acid supply to the brain. Several
      lines of investigation have shown the possibility of the involvement of
      glutamatergic dysfunction in the pathogenesis of schizophrenia. Our recent
      finding of decreased CSF asparagine concentration in schizophrenia and its
      positive correlation with the response to neuroleptics may support this
      hypothesis. Recently, free D-serine, an allosteric agonist on NMDA-receptor, has
      been reported to exist in the rat brain, suggesting that D-serine is an intrinsic
      ligand. The pathogeneses of endogenous psychoses might be studied in terms of
      disturbed metabolism of amino acid, as allosteric regulater of neuro-receptor, as
      well as neurotransmitter and precursor of monoamines.

PMID- 1357205
TI  - [Advances in the theory and method of molecular epidemiology].

PMID- 1357206
TI  - [Identification of species and discrimination among their individuals by
      restriction enzyme cleavage of the genomes].

PMID- 1357207
TI  - [Detection of human herpesvirus 6 (HHV-6) DNA by polymerase chain reaction (PCR)
      and restriction fragment length polymorphism (RFLP) of HHV-6 DNA].

PMID- 1357208
TI  - [Detection of HFRS Hantaan virus RNA sequences by PCR].

PMID- 1357209
TI  - [Molecular epidemiologic examination of group-A hemolytic streptococci; the
      classification according to restricted enzyme patterns of the chromosomal DNA].

PMID- 1357210
TI  - [Application of ribotyping to the identification and molecular epidemiology of
      staphylococci].

PMID- 1357211
TI  - [Molecular epidemiology of Chlamydia trachomatis by DNA restriction endonuclease
      analysis].

PMID- 1357212
TI  - [The application of DNA studies to leptospirosis].

PMID- 1357213
TI  - [Characterization of Trypanosoma cruzi isolates, using restriction enzyme
      analysis of kinetoplast DNA].

PMID- 1357214
TI  - [Reagents and their lists which are essential for DNA diagnosis and molecular
      epidemiology of pathogenic microbials].

PMID- 1357215
TI  - [Effect of a long-term oral ammonia administration on immunoreactive-somatostatin
      concentrations of rat stomach].
AB  - The effect of a long-term oral ammonia administration on immunoreactive
      somatostatin concentrations was investigated in rat stomach. The gastric ir
      somatostatin concentrations in the group treated with 0.01% ammonia (pH 9.6) for
      four weeks were significantly higher than those in both the group treated with
      0.1% ammonia (pH 10.4), 0.1 mM-NaOH (pH 9.6), or distilled water (pH 7.0) for
      four weeks and the group treated with 0.01% ammonia for two weeks. On the
      contrary, ir-somatostatin levels in the gastric juice and serum tended to
      decrease with ammonia administration. Further, ammonia administration
      significantly induced the decrease in mucosal thickness in the pyloric gland area
      and parietal cell numbers in a dose- and time-dependent manner. From these
      findings, it was suggested that a long-term oral treatment with 0.01% ammonia,
      which was clinically estimated as the concentration of the gastric juice in
      patients with Helicobacter pylori infection, induced not only atrophic changes on
      gastric mucosa, but the inhibitory effect on somatostatin secretion in rat
      stomach.

PMID- 1357216
TI  - [A study of DNA ploidy pattern, proliferation index and PCNA in duodenal
      carcinoma].
AB  - 12 cases of duodenal carcinoma were studied for nuclear DNA ploidy patterns, the
      proliferation index (PI), proliferating cell nuclear antigen (PCNA) positive
      score (1 = 0-25%, 2 = 26-50%, 3 = 51-75%, 4 = 76-100%) and PCNA positive rate.
      DNA aneuploidy was observed in 9 cases (75%) and PCNA staining was positive in 11
      cases (91.6%). DNA ploidy patterns, PI, PCNA positive scores and positive rates
      were not related to each other. No relationship DNA ploidy patterns for PCNA
      positive scores and PCNA positive rates could be found. The relationship between
      PI and PCNA positive score was found not to be significant (P less than 0.10). PI
      was revealed to correlate significantly (P less than 0.05) to PCNA positive rate.

PMID- 1357217
TI  - Postsynaptic potentiation of neurotransmission by neurokinin A in rat vas
      deferens.
AB  - Effects of neurokinin A (NKA) on sympathetic neurotransmission were studied in
      rat vas deferens. Although neither prazosin, an alpha 1-adrenoceptor blocker, nor
      alpha, beta-methylene adenosine triphosphate, a P2-purinoceptor blocker,
      inhibited the NKA-induced contractions in the epididymal site, high concentration
      of NKA-induced contractions in the prostatic site were slightly decreased by
      either of the two blockers. Treatment with guanethidine, which prevents the
      release of sympathetic transmitters from presynaptic nerve endings, also had no
      effect on NKA-induced contractions in either site. To investigate the effects of
      NKA on the adrenergic and purinergic neurotransmission in more detail, we
      measured transmitter release by using [3H]norepinephrine or [14C]adenosine.
      Neither spontaneous or nor evoked 3H efflux, indicating NE release, was affected
      by NKA in either site. NKA enhanced 14C efflux, indicating ATP release, evoked by
      electrical stimulation in the epididymal site, which may be originated from
      smooth muscle. In the prostatic site, contractions induced by electrical
      stimulation were enhanced in spite of no increase in 3H or 14C efflux. These
      results suggest that: 1) NKA has no effect on presynaptic nerve terminals in both
      sites, 2) NKA potentiates the effects of neurotransmitters in the prostatic site,
      and 3) NKA modulates the neurotransmissions.

PMID- 1357218
TI  - [Expression of c-H-ras, c-erb B1 and c-erb B2 gene products in human bladder
      cancer].
AB  - To investigate the expression of c-H-ras (p21), c-erb B1 (EGFR) and c-erb B2
      (p185) gene products in human bladder cancer, immunohistochemical studies using
      monoclonal antibodies to these proteins were performed on formaline fixed (within
      15 hours)-paraffin sections of tumor tissues from 20 patients with bladder
      cancer, normal appearing adjacent bladder (non-tumor) tissues from 11 of the 20
      patients, and normal bladder tissues from 3 patients who died of non-cancerous
      diseases as control. p21 Positive staining was demonstrated in the superficial
      cells of urothelium in 1 of 3 controls, also in 5 of 20 tumor tissues compact
      cells without vacuole in cells which have an increased nuclear/cytoplasmic ratio.
      Seven of 11 non-tumor tissues indicated positive staining either in superficial
      layer only or in whole layers of urothelium, and 1 of the latter group reacted
      with the monoclonal antibody to human bladder cancer produced in our laboratory.
      EGFR was found in 5 of 20 tumor tissues and 7 of 11 non-tumor tissues, but not in
      controls. Most EGFR positive tissues also indicated p21 positivity except in 1 of
      the tumor tissues. p185 Positive staining was demonstrated in 9 of 20 tumor
      tissues and 5 of 11 non-tumor tissues, but not in the controls. Furthermore, 5 of
      6 tumor tissues from the patients with lymph node metastasis indicated p185
      positivity. These results suggest that both p21 and EGFR may have a role in
      transformation and that p185 has a role in the development of metastasis in some
      urothelial malignancies.

PMID- 1357219
TI  - [Structural characteristics of Apo B and ApoC-III genes in patients with ischemic
      heart disease].

PMID- 1357221
TI  - [Role of urapidil in the treatment of arterial hypertension].

PMID- 1357220
TI  - [Soluble guanyl cyclase of blood platelets and heart of rats with experimental
      myocardial ischemia].
AB  - The activity of soluble guanylate cyclase (GC) and its regulation in the
      platelets and heart of normal rats and rats with experimental acute myocardial
      ischemia provoked by coronary ligation was examined. There was a synchronous
      reduction in platelet and heart GC activity immediately following 15 minutes
      after surgery along with a drastically marked drop in genuine baseline activity
      (with Mg2+) to 19 and 40% in the platelets and heart (both ischemic and intact
      areas), respectively. Following 24 hours, GC activity insignificantly rose (up to
      35.5%) in the platelets with Mg2+, that with Mn2+ remained unchanged; in the
      ischemic area it decreased much more (to 30%), whereas in the intact area it
      partially restored (up to 70%). The stimulating effect of DTT on platelet GC
      activity 15 minutes after the surgery drastically rose (from 2.8 to 8), then
      returning to normal 24 hours later. The findings show an enhancement in free
      radical processes typical of ischemia and indicate their high response of
      platelet GC at the earliest stages. Sodium nitroprusside-induced activation of
      myocardial GC diminished in the ischemic area in 15 minutes and virtually lacked
      in 24 hours. There was a less pronounced decrease in GC activation in the intact
      area. It is suggested that lower enzymatic activatibility is associated with heme
      loss. The absence of sodium nitroprusside-induced stimulation of platelet GC both
      in health and in the abnormality under question may be due to primary heme
      enzymatic deficiency.

PMID- 1357222
TI  - [Hyperbaric oxygenation and antianginal agents: effects on blood levels of
      malondialdehyde and activities of antioxidative enzymes in patients with ischemic
      heart disease].
AB  - The time course of serum levels of malonic dialdehyde and red blood cell activity
      of antioxidative enzymes, such as superoxide dismutase and glutathione
      peroxidase, was assessed from the outcomes of hyperbaric oxygenation combined
      with antianginal therapy in 38 patients with functional classes II-III stable
      angina on effort without clinical manifestations of circulatory failure.
      Hyperbaric oxygenation involved 10-12 sessions at 1.5 ata during 40 min each. The
      antianginal agents (long-acting nitrates, beta-adrenoblockers, nifedipine) were
      given in median therapeutical doses. The control group included 26 patients who
      had hyperbaric oxygenation in the same fashion without taking antianginal drugs.
      The criteria for beneficial therapy were a reduction in the number of anginal
      episodes and the nitroglycerin tablets used, an increase in exercise tolerance,
      as evidenced by repeated bicycle ergometric test. The positive clinical effect of
      a hyperbaric oxygenation course was shown to be accompanied by higher activity of
      superoxide dismutase in the red blood cells. The use of nifedipine in the
      multimodality anginal therapy prevents the hyperbaric oxygenation-induced
      increase in serum malonic dialdehyde levels.

PMID- 1357223
TI  - High glucose-induced proliferation in mesangial cells is reversed by autocrine
      TGF-beta.
AB  - We investigated the effects of glucose concentration in serum-free media on the
      proliferative growth response of a cultured murine mesangial cell line. Raising
      the ambient D-glucose concentration from 100 mg/dl to 450 mg/dl stimulated cell
      proliferation after 24 to 48 hours but had a growth inhibitory effect after 72 to
      96 hours of incubation. This biphasic proliferative response to high glucose
      concentration was not mediated by the elevated osmolarity of the medium and did
      not occur when L-glucose was used. The early phase of glucose-induced
      proliferation was associated with increased expression of the immediate early
      genes c-myc and egr-1 as well as with induction of the S-phase related
      proliferating nuclear cell antigen (PCNA). Several lines of evidence indicated
      that the late phase of glucose-induced growth inhibition was mediated by the
      bioactivation of endogenous transforming growth factor beta (TGF-beta).
      Neutralizing antibody against TGF-beta prevented the late inhibitory effects of
      glucose on proliferation. On the other hand, exogenous TGF-beta (1 ng/ml)
      significantly inhibited basal proliferation in mesangial cells. Furthermore,
      Northern blot analysis revealed that TGF-beta 1 mRNA was induced by 450 mg/dl
      glucose in the medium after 48 to 72 hours, but not after 24 hours. Cell cycle
      analysis demonstrated that mesangial cells incubated in high glucose for 24 hours
      have a higher percentage of cells in the S-G2 phase of the cell cycle compared
      with cells grown in normal glucose concentration. After 48 hours of culture in
      elevated glucose concentration, the percentage of cells in S-G2 phase was
      decreased, and became comparable to that of cells in normal glucose
      concentration. However, the addition of neutralizing anti-TGF-beta antibody
      stimulated the progression of cells towards S-G2 in high glucose medium after 48
      hours. The findings of this study demonstrate a biphasic growth response of
      mesangial cells when they were cultured in high glucose concentration; initially
      there was a transient stimulation of replication for 24 to 48 hours followed by a
      sustained inhibition after longer incubation periods. This inhibition may be
      mediated by the glucose-induced synthesis and/or bioactivation of TGF-beta which
      can inhibit proliferation of mesangial cells in an autocrine fashion.

PMID- 1357224
TI  - Role of NMDA and non-NMDA receptors in excitatory postsynaptic potentials in rat
      suprachiasmatic nucleus neurons.

PMID- 1357225
TI  - Maternal and other factors of cryptorchidism--a case-control study in Japan.
AB  - A case-control study of cryptorchidism was undertaken in Japan. A hundred and
      eight mothers of children with cryptorchidism and mothers of their matched
      controls were surveyed. After 4 pairs which consisted of one of twin siblings
      either in the cases or the controls were excluded, 104 paired data of singletons
      were analyzed. As a result, a significantly smaller proportion of the case
      mothers had suffered from vomiting during the index pregnancy than that of the
      control mothers (odds ratio, or OR = 0.50, 95% confidence interval, or CI 0.28
      0.89). A significantly larger proportion of the case mothers had delivered the
      index child by vacuum or breech extraction, or Caesarean section than that of the
      control mothers (OR = 2.09, 95% CI 1.01-3.98). A significantly larger proportion
      of the case mothers had never breast-fed the index child than that of the control
      mothers (OR = 3.50, 95% CI 1.20-10.21). Significantly larger proportions of the
      cases had inguinal hernia (OR = 9.00, 95% CI 1.29-62.97), or congenital cardiac
      diseases (OR = 8/0, p < 0.05) than those of the controls. It was inferred that
      endogenous hormonal milieu of a mother, rather than exogenous hormones, might be
      associated with the occurrence of cryptorchidism.

PMID- 1357226
TI  - [Interhospital 92. New impressions].

PMID- 1357227
TI  - Unusual clinical presentation in two boys with cytochrome c oxidase deficiency.

PMID- 1357228
TI  - Biochemical and DNA markers of X-linked hypophosphataemic rickets: a study of
      sporadic cases.

PMID- 1357229
TI  - Screening for mutations in the gene encoding factor IX.

PMID- 1357230
TI  - Gene diagnosis and carrier detection in Hunter syndrome by the iduronate-2
      sulphatase cDNA probe.

PMID- 1357232
TI  - A COL3A1 glycine 1006 to glutamic acid substitution in a patient with Ehlers
      Danlos syndrome type IV detected by denaturing gradient gel electrophoresis.

PMID- 1357231
TI  - Bifunctional enzyme deficiency: identification of a new type of peroxisomal
      disorder in a patient with an impairment in peroxisomal beta-oxidation of unknown
      aetiology by means of complementation analysis.

PMID- 1357233
TI  - Colonic epithelial cell proliferation in a rat model of nongenotoxin-induced
      colonic neoplasia.
AB  - BACKGROUND: The effect on colonic cell proliferation of poligeenan, a
      nongenotoxic polysaccharide that induces colon tumors in rats, was compared with
      guar gum and carrageenan. EXPERIMENTAL DESIGN: Fischer 344 rats were fed a basal
      diet supplemented with carrageenan and poligeenan fibers for up to 91 days. The
      quantitative levels of proliferation, location of the proliferating cells, and
      the ability of the mucosa to readapt by removing the experimental fibers from the
      diet were tested. RESULTS: The mucosal epithelium exhibited a 5-fold increase in
      thymidine kinase activity in both the carrageenan and poligeenan groups.
      Proliferating cells appeared at the luminal surface only in the poligeenan
      treated rats, and the number of proliferating cells in the upper third of the
      crypt increased 35-fold. A second and third set of animals were fed one of the
      three test diets for either 28 or 64 days, followed by a 28-day recovery period.
      Proliferation in the guar- and carrageenan-treated groups returned to basal
      levels. In poligeenan-treated rats, thymidine kinase levels, and proliferating
      cells in the upper third of the crypt remained 2- and 11-fold, respectively,
      above controls. CONCLUSIONS: The difference in recovery time between the
      poligeenan group and the others, and the luminal location of proliferating cells
      may prove useful as markers in understanding early events in the carcinogenic
      process induced by a nongenotoxin.

PMID- 1357234
TI  - Alterations in the beta-adrenergic receptor system after hypothermic ischemia in
      hearts with preischemic beta-receptor desensitization.
AB  - Although hypothermic cardioplegic arrest is a basic method of myocardial
      protection in cardiac surgery, the beta-adrenergic receptor (BAR) system has been
      little investigated in the heart subjected to hypothermic ischemia. Additionally,
      although the hypothermic arrest is often induced in hearts with preischemic
      desensitization of the BAR system by preceding congestive heart failure, the
      functional state of the BAR system after ischemia has not been studied in these
      hearts. We investigated alterations in the BAR system after hypothermic ischemia
      in normal rat hearts and in those with preischemic desensitization of the BAR
      system produced with isoproterenol (ISP: 400 micrograms/kg/hr for 24 hr). Both
      normal and BAR-desensitized hearts were isolated and subjected either to 40 min
      of hypothermic (10 degrees C) global ischemia followed by 40 min of reperfusion
      or subjected to time-matched aerobic perfusion with modified Krebs-Henseleit
      solution. At the end of perfusion (1) BAR binding properties with [3H]CGP-12177
      and adenylate cyclase activity were measured in crude membrane fraction and (2)
      the inotropic response to ISP (delta LV + dP/dtmax) was evaluated in an
      isovolumetric contracting heart preparation. Following reperfusion, normal hearts
      without desensitized BAR showed a higher Bmax value than those of nonischemic
      time-matched hearts (41.8 +/- 3.1 vs 35.4 +/- 2.4 fmole/mg protein, P less than
      0.05), whereas the Kd value was in a similar range in the two groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1357235
TI  - Beta-blocking drug prophylaxis after coronary artery bypass operations.

PMID- 1357236
TI  - Development of a sensitive and inexpensive micropush-pull technique for the
      continuous analysis of brain neurotransmitters and metabolites in vivo.
AB  - A new, sensitive, convenient, inexpensive and low-maintenance miniaturized triple
      cannula system (Zhange et al., 1990) for the push-pull perfusion of brain tissue
      has been constructed, and tested for its ability to exchange substances in rats,
      both in vitro and in vivo. In vitro: the cannula was immersed in a vial filled
      with 1.5 ml of a 1 microM standard solution of norepinephrine, dopamine, and
      their metabolites. Artificial cerebrospinal fluid was perfused through the
      system. Perfusate was collected at rates of 1, 2, 5, 10 and 20 microliters/min
      over 10 min. The recovery rate of the biogenic amines (using high performance
      liquid chromatography) at 10-min intervals for 60 min was consistent (57 +/-
      1.31%) in low flow rate groups (1 approximately 10 microliters/ml). In vivo:
      [3H]choline (3 microCi, 35 nmol) was infused (6 min) into the lateral ventricle
      and collected by micropush-pull at 10-min intervals for 180 min, from the
      cerebellomedullary cistern and hippocampus. The highest [3H]choline count was
      reached within 10 min after infusion. Levels returned to baseline within 20 min
      following infusion of the tracer. The micropush-pull cannula was also adapted for
      chronic brain perfusion in vivo. Recovery of perfused fast green dye (0.00025%)
      was comparable (83 +/- 1.75%), using the same cannula for 3 sampling periods
      within 1 month in a freely moving rat. A cresyl violet analysis showed minimal
      damage to the brain tissue, with gliosis only evident in a narrow margin along
      the cannula track. Thus the micropush-pull technique is highly efficient in terms
      of exchange of material, causes minimal damage of brain tissue, and can be used
      chronically in awake animals. These data have been presented in preliminary form
      at the 1991 ASPET meetings (Zhang et al., 1991).

PMID- 1357237
TI  - Evaluation of quinolinic acid induced excitotoxic neurodegeneration in rat
      striatum by quantitative magnetic resonance imaging in vivo.
AB  - Excitotoxic neurodegeneration in the rat striatum was induced by direct injection
      of quinolinic acid. The degree of damage was evaluated in vivo 1 day later by
      quantitative magnetic resonance imaging (MRI) and 7 days later in the same
      animals by measuring the activities of the neuronal marker enzymes choline
      acetyltransferase and glutamic acid decarboxylase. Striatal damage assessed using
      the two approaches was highly correlated. Moreover the cerebroprotective efficacy
      of the N-methyl-D-aspartate receptor antagonist CGP 40116 was indistinguishable
      based on all analytical parameters. MRI, however, was more reproducible than the
      enzymatic methods and was faster and simpler for routine analyses of excitotoxic
      damage and cerebroprotection in vivo.

PMID- 1357239
TI  - [Bone marrow transplantation and organ transplantation can cure hereditary
      metabolic diseases].

PMID- 1357238
TI  - [Treatment of angina pectoris with beta blockaders can be optimized by isotope
      techniques].

PMID- 1357240
TI  - [How dangerous are beta 2 stimulants for patients with heart diseases complicated
      with obstructive lung diseases?].

PMID- 1357241
TI  - [Is vole fever (nephropathia epidemica) spreading in the south of Sweden?].

PMID- 1357242
TI  - Randomised controlled trial of cost-effectiveness of lithotripsy and open
      cholecystectomy as treatments for gallbladder stones.
AB  - Inpatient extracorporeal shockwave lithotripsy for treatment of gallbladder
      stones has not previously been compared with open cholecystectomy in terms of
      cost-effectiveness. In a randomised controlled trial, 163 patients, stratified by
      gallstone bulk (over 4 cm3 or not), were randomised to lithotripsy or
      cholecystectomy (38 large-bulk and 27 small-bulk cholecystectomy; 37 large-bulk
      and 61 small-bulk lithotripsy) and followed up for 1 year. Both treatments gave
      significant health gains in terms of a reduction in episodes of biliary pain,
      improved perceived health status, and symptom relief, but few differences between
      treatments were found. There was some evidence that biliary-pain episodes were
      less severe after cholecystectomy. Cholecystectomy patients also had greater
      improvements in mean health gain for three related symptoms: vomiting, feeling
      sick, and fatty-food upset. However, there were no differences between groups in
      perceived health status. Among lithotripsy patients, health gain was not related
      to stone clearance. Lithotripsy was more expensive than cholecystectomy,
      principally because of the costs of the inpatient stay and adjuvant bile-salt
      therapy. Conventional lithotripsy appears at least as cost-effective as
      cholecystectomy for patients with small-bulk stones but less cost-effective for
      those with large-bulk stones. To some extent treatment choice can be guided by
      patient preference.

PMID- 1357243
TI  - 20 years or more of follow-up of living kidney donors.
AB  - The perioperative and long-term risks for living kidney donors are of concern. We
      have studied donors at the University of Minnesota 20 years or more (mean 23.7)
      after donation by comparing renal function, blood pressure, and proteinuria in
      donors with siblings. In 57 donors (mean age 61 [SE 1]), mean serum creatinine is
      1.1 (0.01) mg/dl, blood urea nitrogen 17 (0.5) mg/dl, creatinine clearance 82 (2)
      ml/min, and blood pressure 134 (2)/80 (1) mm Hg. 32% of the donors are taking
      antihypertensive drugs and 23% have proteinuria. The 65 siblings (mean age 58
      [1.3]) do not significantly differ from the donors in any of these variables: 1.1
      (0.03) mg/dl, 17 (1.2) mg/dl, 89 (3.3) ml/min, and 130 (3)/80 (1.5) mm Hg,
      respectively. 44% of the siblings are taking antihypertensives and 22% have
      proteinuria. To assess perioperative mortality, we surveyed all members of the
      American Society of Transplant Surgeons about donor mortality at their
      institutions. We documented 17 perioperative deaths in the USA and Canada after
      living donation, and estimate mortality to be 0.03%. We conclude that
      perioperative mortality in the USA and Canada after living-donor nephrectomy is
      low. In long-term follow-up of our living donors, we found no evidence of
      progressive renal deterioration or other serious disorders.

PMID- 1357244
TI  - Infant cerebral cortex phospholipid fatty-acid composition and diet.
AB  - It has not been established whether nutrition in early infancy affects subsequent
      neurodevelopment and function. If there is an effect, it seems probable that the
      essential fatty acids and their metabolites, the major constituents of brain
      structure, will be the most susceptible to dietary influence. We determined the
      phospholipid fatty-acid composition of cerebral cortex grey matter obtained from
      20 term and 2 preterm infants who had died of "cot deaths" and related results to
      the milk diet the infants had received. Tissues were analysed by gas
      chromatography. The mean weight percentage of docosahexaenoic acid was
      significantly greater (p less than 0.02) in 5 breast-milk-fed infants (9.7%) than
      in 5 age-comparable formula-milk-fed infants (7.6%). In these formula-fed babies,
      the overall percentage of long-chain polyunsaturated fatty acids was maintained
      by increased incorporation of the major n-6 series fatty acids. In 1 formula-fed
      preterm infant, in whom the lowest concentration of cortical docosahexaenoic acid
      was found, the compensatory effect was only partial with both n-9 series
      eicosatrienoic acid or Mead acid and docosatrienoic acid also detected in the
      phospholipid. Supplementation of formula milks for term infants with
      docosahexaenoic acid and those for preterm infants with both docosahexaenoic and
      arachidonic acid could prove beneficial to subsequent neurodevelopment.

PMID- 1357245
TI  - Inhaled nitric oxide in persistent pulmonary hypertension of the newborn.
AB  - Nitric oxide (NO) has vasodilatory effects on the pulmonary vasculature in adults
      and animals. We examined the effects on systemic oxygenation and blood pressure
      of inhaling up to 80 parts per million by volume of NO at FiO2 0.9 for up to 30
      minutes by 6 infants with persistent pulmonary hypertension of the newborn
      (PPHN). In all infants this treatment rapidly and significantly increased
      preductal oxygen saturation (SpO2); in 5 infants postductal SpO2 and oxygen
      tensions also increased. Inhalation of NO did not cause systemic hypotension or
      raise methaemoglobin. These data suggest that low levels of inhaled NO have an
      important role in the reversal of hypoxaemia due to PPHN.

PMID- 1357247
TI  - Environmental pollution: it kills trees, but does it kill people?

PMID- 1357246
TI  - Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the
      newborn.
AB  - We studied the effects of inhaled nitric oxide (NO) in 9 newborn infants with
      severe persistent pulmonary hypertension (PPHN) who were candidates for
      extracorporeal membrane oxygenation treatment. With low doses of NO (10-20 ppm)
      all showed rapid improvement in oxygenation without reduction of systemic blood
      pressure. In 6 infants treated with inhaled NO for 24 h, clinical improvement was
      sustained at 6 ppm.

PMID- 1357248
TI  - New treatment for tyrosinaemia.

PMID- 1357249
TI  - Volunteering for research.

PMID- 1357250
TI  - Post-term induction: don't kill the messenger.

PMID- 1357251
TI  - Colons and keyholes.

PMID- 1357252
TI  - A large focus of alveolar echinococcosis in central China.
AB  - Human alveolar echinococcosis (AE) is a rare and highly pathogenic helminthic
      zoonosis due to infection with the intermediate stage of the small fox tapeworm,
      Echinococcus multilocularis. Parasite transmission is restricted to northern
      latitudes, including central and north China, from where few clinical and no
      detailed community studies have been reported. In August, 1991, 65 (5%) of 1312
      people residing in three rural communes of Zhang County, Gansu Province, China
      were diagnosed as having hepatic AE after mass ultrasound scanning with
      serological back-up. This represents one of the highest prevalence rates of AE
      ever recorded. It is also the first time that mass ultrasound scanning and
      serology have been used together in an AE endemic region. The region was selected
      one year earlier, when a preliminary serosurvey on 606 unselected people in the
      same locality resulted in an 8.8% serum antibody positive rate with a 76% rate of
      confirmation of hepatic AE in 37 individuals who could be followed up in 1991.
      Seropositivity rates varied for villages between 0 and 20.5%. Overall, females
      (7.8%) had a significantly greater risk of infection than males (2.5%),
      especially in the 31-50 age group, a difference which may be related to contact
      with dogs and dog faeces over many years. Age-specific prevalence of AE increased
      from 0% in the under 5-year group to 8.2% in those aged 31-50. The youngest case
      was 11 years and the mean age of diagnosis was 40 years. Adult tapeworms of E
      multilocularis were identified from the small intestines of 10% of domestic dogs.
      Sylvatic animal hosts of the parasite have not yet been identified. The high
      prevalence of human AE in this region of central China is most probably due to
      semi-domestic transmission of E multilocularis between wild rodents and dogs,
      together with the poverty and poor hygiene in these rural communities.

PMID- 1357254
TI  - Anatomy and the medical school curriculum.

PMID- 1357253
TI  - Prospective evaluation of laparoscopic-assisted colectomy in an unselected group
      of patients.
AB  - Laparoscopic technology is likely to have an increasing impact on surgical
      procedures that have previously required an open approach. We have prospectively
      evaluated laparoscopic colectomy in 40 patients requiring elective colonic
      excision mainly for malignant disease. 33 of 40 patients had a successfully
      completed laparoscopic colectomy, although there was one postoperative death.
      Seven operations were unsuccessful and required conversion to conventional open
      laparotomy. Morbidity was low with no wound infections and only two chest
      infections in the 32 survivors. Early mobilisation and discharge from hospital
      (mean 8 days) was a notable feature. Previous abdominal surgery was not an
      absolute contraindication to laparoscopic colectomy. However, the inability to
      palpate the colon directly to confirm the site of laparoscopically impalpable
      lesions leads us to recommend contrast radiology to confirm the location of
      colonoscopically diagnosed lesions before laparoscopically assisted colectomy.
      Preliminary pathological assessment of resected tumour specimens revealed a
      satisfactory tumour clearance. We conclude that laparoscopic colectomy is a
      feasible operation in most patients and leads to a substantial patient benefit
      without compromising the chance of a surgical cure of cancer.

PMID- 1357255
TI  - The Hong Kong Academy of Medicine.

PMID- 1357256
TI  - Health-care issues add to Bush's woes.

PMID- 1357257
TI  - Two lessons from cardiology.

PMID- 1357258
TI  - No new HIV-like virus.

PMID- 1357259
TI  - Preventing international spread of HIV infection.

PMID- 1357260
TI  - Efficacy of Haemophilus influenzae type B conjugate vaccine in Oxford region.

PMID- 1357261
TI  - Creutzfeldt-Jakob legacy for Australian women treated with human pituitary
      gonadotropins.

PMID- 1357262
TI  - Pathophysiology of obesity.

PMID- 1357263
TI  - Pathophysiology of obesity.

PMID- 1357264
TI  - Cytoreduction in ovarian cancer.

PMID- 1357265
TI  - Pathophysiology of obesity.

PMID- 1357266
TI  - Stapled anastomoses and colon cancer recurrence.

PMID- 1357267
TI  - Neonatal screen for hereditary tyrosinaemia type I.

PMID- 1357268
TI  - Role of amyloid beta-protein in Alzheimer's disease.

PMID- 1357269
TI  - Low back pain associated with streptokinase.

PMID- 1357270
TI  - Role of amyloid beta-protein in Alzheimer's disease.

PMID- 1357271
TI  - Antiplatelet therapy in thrombotic thrombocytopenic purpura.

PMID- 1357272
TI  - Thrombolysis for pulmonary embolism.

PMID- 1357273
TI  - Food intake and platelet aggregability.

PMID- 1357274
TI  - Inferior vena caval filters and systemic prothrombin activation in orally
      anticoagulated patients.

PMID- 1357275
TI  - French cancer research funding from ARC.

PMID- 1357276
TI  - Suicide in prison in Auckland.

PMID- 1357277
TI  - NCEPOD and UK specialist training.

PMID- 1357278
TI  - The NHS as a developing market for cancer research.

PMID- 1357279
TI  - The NHS as a developing market for cancer research.

PMID- 1357280
TI  - Smoking as a contributory cause of death on death certificates.

PMID- 1357281
TI  - Reduction in human fetal umbilical-placental vascular resistance by glyceryl
      trinitrate.

PMID- 1357282
TI  - Acamprosate as cause of erythema multiforme contested.

PMID- 1357283
TI  - Acute disseminated epidermal necrosis due to omeprazole.

PMID- 1357284
TI  - Didanosine as probable cause of Stevens-Johnson syndrome.

PMID- 1357285
TI  - Bradycardia due to anthracyclines.

PMID- 1357287
TI  - Viral load and mother-to-infant HIV transmission.

PMID- 1357286
TI  - Susceptibility of low-density lipoproteins to oxidation in coronary bypass
      patients.

PMID- 1357289
TI  - Bartter's syndrome with impairment of growth hormone secretion.

PMID- 1357288
TI  - Continuous subcutaneous apomorphine as replacement for levodopa in severe
      parkinsonian patients after surgery.

PMID- 1357290
TI  - Risk of strut fracture of Bjork-Shiley convexo-concave valves.

PMID- 1357291
TI  - Risk of strut fracture of Bjork-Shiley convexo-concave valves.

PMID- 1357292
TI  - Colonisation of oropharynx with staphylococci after penicillin in neutropenic
      patients.

PMID- 1357293
TI  - Rice and glucose oral rehydration solutions in patients with high ileostoma fluid
      output.

PMID- 1357294
TI  - Long-term symptomless HIV-1 infection in recipients of blood products from a
      single donor.
AB  - There have been reported cases of long-term symptomless human immunodeficiency
      virus type 1 (HIV-1) infection, but it is not clear whether the benign course of
      infection was due to host, viral, or other unknown factors. During follow-up of
      subjects with transfusion-acquired HIV-1 infection in New South Wales, Australia,
      we identified a group of 6 subjects who had been infected through a single common
      donor. We were therefore able to study the contributions of various factors to
      the course of infection. Throughout follow-up (range 6.8-10.1 years after
      infection), 5 of the recipients and the donor (last follow-up 10.2 years after
      infection of the first recipient) remained clinically free of symptoms, with
      normal CD4 cell counts and no p24 antigenaemia. HIV-1 was isolated from only 1
      recipient; the isolate did not induce syncytia in a SUPT1 co-culture assay and
      had a limited in-vitro host range. 1 infected recipient (who had received
      extensive immunosuppressive treatment for systemic lupus erythematosus) developed
      Pneumocystis carinii pneumonia and died 4.3 years after infection. The frequency
      of progression to AIDS or a CD4 cell count below 0.50 x 10(9)/l was significantly
      lower among the 6 subjects with a common donor (1/6) than among 101 other HIV
      infected transfusion recipients for whom data from 7 years of follow-up were
      available (94/101; p less than 0.0001). These findings suggest that the subjects
      were infected by a less virulent strain of HIV-1. The identification of this
      group of subjects should stimulate a search for other similar groups, which will
      provide important information on the immunopathogenesis of HIV-1 disease.

PMID- 1357295
TI  - Haemodynamic effects of tracheal compared with intravenous adrenaline.
AB  - If intravenous access is not available during cardiopulmonary resuscitation,
      tracheal administration of adrenaline 0.02 mg/kg, twice the intravenous dose, is
      recommended. In a randomised crossover study we investigated the haemodynamic
      effects of low doses of tracheal versus intravenous adrenaline. 12 anaesthetised
      patients having a hip replaced received one dose of adrenaline intravenously (0.1
      microgram/kg) and the other tracheally (0.5 microgram/kg). There was a mean
      increase in systolic arterial pressure of 40.5 mm Hg (range 16-81) after the
      intravenous injection, with little effect on heart rate. Tracheal adrenaline had
      no effect on arterial pressure or heart rate. Thus low doses of tracheal
      adrenaline have no haemodynamic effects. We believe that the recommended tracheal
      dose of twice the intravenous dose is likely to be ineffective for the treatment
      of cardiac arrest. Animal studies suggest that a tracheal dose at least ten times
      the intravenous dose is required.

PMID- 1357296
TI  - Oligonucleotide genotyping of HLA polymorphism on microtitre plates.
AB  - Molecular analysis of mutations and polymorphisms that are of medical importance
      requires both accuracy and simplicity. In organ transplantation there is a need
      for an HLA typing procedure that combines the remarkable accuracy of
      oligonucleotide genotyping with the simplicity of conventional serological
      typing. We describe a simple semiautomated method of HLA class II typing
      consisting of an oligonucleotide hybridisation assay done on microtitre plates
      followed by automatic colorimetric reading. Individual HLA-DR generic typing for
      30 DR specificities, including subtypes of DR1, DR2, DR13, DR14, and DR52, is
      done on a single plate. The entire typing assay can be completed in less than 4
      hours. The procedure has been validated on more than a thousand haplotypes in
      prospective DR typing of kidney transplant patients, leukaemic patients, and
      their potential donors. The simplicity of this assay makes it suitable for
      routine laboratory use. It can be applied to genetic testing in general,
      including the testing of patients with multiple mutations.

PMID- 1357297
TI  - Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary
      embolism. Research Committee of the British Thoracic Society.
AB  - The optimum duration of anticoagulation therapy for deep-vein thrombosis (DVT)
      and pulmonary embolism (PE) is not clear. We have carried out a multicentre
      comparison of 4 weeks' and 3 months' anticoagulation in patients admitted to
      hospital with acute DVT, PE, or both. Of 712 patients enrolled, 358 were assigned
      4 weeks' treatment and 354 3 months'. Objective confirmation of the diagnosis was
      obtained in 71%. PE caused or contributed to death in 7 patients (3 treated for 4
      weeks, 4 for 3 months). Adverse effects were uncommon, although 1 patient (4-week
      group) died of haemorrhage. The numbers of patients whose thromboembolism failed
      to resolve on treatment was lower in the 3-month group than in the 4-week group
      (13 [3.7%] vs 24 [6.7%], p = 0.10) as was the number who had recurrences (14
      [4.0%] vs 28 [7.8%], p = 0.04). Among patients with postoperative DVT or PE the
      rate of treatment failure and recurrence was low (2.6%) and there was little
      difference between the treatment groups. By contrast, among medical patients the
      rate was 12.8%, with a clear difference in favour of 3 months' treatment. If
      venous thromboembolism arises after surgery, 4 weeks of anticoagulation should be
      adequate. In other settings, patients with new DVT, PE, or both, who do not have
      a persisting underlying cause or risk factor should receive anticoagulants for 3
      months.

PMID- 1357298
TI  - Systemic chimerism in human female recipients of male livers.
AB  - We have previously reported data from clinical and laboratory animal observations
      which suggest that organ tolerance after transplantation depends on a state of
      balanced lymphodendritic cell chimerism between the host and donor graft. We have
      sought further evidence to support this hypothesis by investigating HLA
      mismatched liver allograft recipients. 9 of 9 female recipients of livers from
      male donors had chimerism in their allografts and extrahepatic tissues, according
      to in-situ hybridisation and molecular techniques 10 to 19 years
      posttransplantation. In 8 women with good graft function, evidence of the Y
      chromosome was found in the blood (6/8), skin (8/8), and lymph nodes (7/8). A
      ninth patient whose transplant failed after 12 years from recurrent chronic viral
      hepatitis had chimerism in her lymph nodes, skin, jejunum, and aorta at the time
      of retransplantation. Although cell migration is thought to take place after all
      types of transplantation, the large population of migratory cells in, and the
      extent of their seeding from, hepatic grafts may explain the privileged
      tolerogenicity of the liver compared with other organs.

PMID- 1357299
TI  - Implications of pulsatile stretch on growth of saphenous vein and mammary artery
      smooth muscle.
AB  - Internal mammary artery (IMA) coronary bypass grafts have a higher patency than
      saphenous vein (SV) grafts. Intimal hyperplasia and occlusion of venous grafts
      result from smooth muscle proliferation. Mechanical factors, such as pulsatile
      stretch, are potential mediators of this process. Smooth muscle cells from IMA
      and SV were cultured on deformable membranes and exposed to pulsatile stretch (60
      cycles/min). This stimulus increased 3H-thymidine incorporation into venous (a
      two-fold increase) but not arterial smooth muscle cells after 24 h. Smooth muscle
      cell numbers from SV, but not IMA, were increased (p less than 0.05) after 6 days
      of stretch. Thus, pulsatile stretch stimulates smooth muscle cell proliferation
      in SV, but not IMA, and may contribute to venous bypass graft disease.

PMID- 1357301
TI  - Born to be fat?

PMID- 1357302
TI  - Nitric oxide and erection.

PMID- 1357300
TI  - Apolipoprotein epsilon 4 homozygosity in young men with coronary heart disease.
AB  - We have compared apolipoprotein E gene polymorphism in 91 Australian men aged 30
      50 who had been referred for coronary angioplasty and in 172 healthy younger men.
      5 of the 19 patients who were less than 40 years of age were homozygous for the
      epsilon 4 allele, representing a 16-fold increase in prevalence compared with
      controls. In patients aged 40-50 the epsilon 4 allele frequency was 60% higher
      than it was in controls. Inheritance of epsilon 4 seems to confer risk of
      premature ischaemic heart disease in males, homozygotes being especially at risk
      at a younger age.

PMID- 1357303
TI  - Preventing cataract.

PMID- 1357304
TI  - When the body clock goes wrong: delayed sleep phase syndrome.

PMID- 1357305
TI  - Importance of complete follow-up of spontaneous fetal loss after amniocentesis
      and chorion villus sampling.
AB  - Women who are the most difficult to trace after amniocentesis or chorion villus
      sampling are often those who have had an adverse pregnancy outcome. To calculate
      total fetal loss figures for use in prenatal counselling we have followed in a
      multicentre study 100% of women who had undergone these procedures. Early
      spontaneous loss (within three weeks of the procedure) and total spontaneous loss
      were much lower after amniocentesis (0.2% and 1.3%, respectively) than after
      chorion villus sampling (1.2% and 2.9%). Four spontaneous fetal losses among the
      20 pregnancies that were the most difficult to follow-up increased the loss rate
      by 0.5% for chorion villus sampling. Risk of early fetal loss after chorion
      villus sampling was related to experience of the operator (relative risk [RR]
      4.3, p = 0.003), and total fetal loss was lower in pregnancies tested at 10
      weeks' or more gestational age compared with those tested before 10 weeks' (RR
      0.4, p = 0.01). A table showing the frequency of each of the seven possible
      outcomes after amniocentesis and chorion villus sampling is useful in counselling
      those considering one or other test.

PMID- 1357306
TI  - Randomised trial of case finding and surveillance of elderly people at home.
AB  - Health screening for old people who live at home has been the subject of debate
      for 30 years or so. It has come to the fore again in the UK with the new emphasis
      on annual assessments by general practitioners (GPs) of those aged 75 or more.
      Screening in the elderly has implications for manpower. How can it best be done?
      We describe here a randomised, controlled study of case finding and surveillance
      in patients aged 65 and over in a general practice in South Wales. Problem
      identification was by a postal questionnaire, focusing on function, that was sent
      at random to 369 eligible patients with subsequent verification and intervention
      by a specially appointed nurse. The 356 controls had no questionnaires and no
      contact with that nurse. The study lasted 3 years, and end-points included
      mortality, self-ratings of quality of life, and health status, and use of all
      services (GP contacts, hospital admission, home help, and so on). Mortality was
      significantly lower in the intervention group (18%) than in the controls (24%)
      (difference 6.0% [95% CI 0.1-11.9%], p less than 0.05). Total number of hospital
      admissions did not differ between intervention and control groups, but duration
      of hospital stay of patients aged 65 to 74 years was significantly shorter in the
      intervention group (difference 4.6 days [95% CI 1.6-7.6], p less than 0.01). An
      increase in visits to a GP was largely offset by a lower number of home visits by
      a GP. Quality-of-life measures revealed no between-group differences, but self
      rated health status was superior in the intervention group. We conclude that the
      use of a postal screening questionnaire with selective follow-up and intervention
      can favourably influence outcome and use of health care resources by elderly
      people living at home.

PMID- 1357307
TI  - "Pseudo-resistant" malaria in tropical countries.

PMID- 1357308
TI  - Breast cancer: environmental factors. Breast Cancer Prevention Collaborative
      Research Group.

PMID- 1357309
TI  - Breast cancer: nutritional factors.

PMID- 1357310
TI  - Uptake of confidential, named HIV testing in Scottish prisons.

PMID- 1357311
TI  - ACE inhibitors and anaphylactoid reactions during venom immunotherapy.

PMID- 1357312
TI  - Anaphylactoid reactions, LDL apheresis with dextran sulphate, and ACE inhibitors.

PMID- 1357313
TI  - Headache recurrence after subcutaneous sumatriptan and early treatment.

PMID- 1357314
TI  - Halofantrine and acute intravascular haemolysis.

PMID- 1357315
TI  - Depressive symptoms in hypercholesterolaemic patients treated with pravastatin.

PMID- 1357316
TI  - Vibrio cholerae O1 septicaemia.

PMID- 1357317
TI  - Risk of pneumonia after hospital treatment for pneumonia.

PMID- 1357318
TI  - Motorcyclists and wind noise.

PMID- 1357319
TI  - Postoperative morbidity and alcohol consumption.

PMID- 1357320
TI  - Patient guidance after 131I therapy: time for change?

PMID- 1357321
TI  - Potential hazards in estimation of gastric intramucosal pH.

PMID- 1357322
TI  - Proton magnetic resonance spectroscopy of brain after cardiac resuscitation.

PMID- 1357323
TI  - Cardiovascular system design and barosaurus.

PMID- 1357324
TI  - Cardiovascular system design and barosaurus.

PMID- 1357325
TI  - MRC and research funding.

PMID- 1357326
TI  - Keep the details in The Lancet.

PMID- 1357327
TI  - Difficulty with MEDLINE searches for randomised controlled trials.

PMID- 1357328
TI  - Charging for health services in developing countries.

PMID- 1357329
TI  - Sequelae after exposure to pesticides.

PMID- 1357330
TI  - Treatment duration before bone marrow transplantation in stage IV neuroblastoma.
      European Bone Marrow Transplant Group Solid Tumour Registry.

PMID- 1357331
TI  - Blood transfusions for severe anaemia in African children.

PMID- 1357332
TI  - Blood transfusions for severe anaemia in African children.

PMID- 1357333
TI  - Possible genomic imprinting in familial adenomatous polyposis.

PMID- 1357334
TI  - The practice of growth monitoring.

PMID- 1357335
TI  - Pre-pregnancy clinics for diabetic women.

PMID- 1357336
TI  - Pre-pregnancy clinics for diabetic women.

PMID- 1357337
TI  - Pre-pregnancy clinics for diabetic women.

PMID- 1357338
TI  - Inappropriate sensor application in pulse oximetry.

PMID- 1357339
TI  - Intravenous immunoglobulin for multifocal motor neuropathy.

PMID- 1357340
TI  - Disinfection of water by sunlight.

PMID- 1357341
TI  - Umbilical cord blood for transplantation.

PMID- 1357342
TI  - Reversible p53 expression in lung cancer.

PMID- 1357343
TI  - Radiation exposure after coronary arteriography.

PMID- 1357344
TI  - Measles mortality in same-sex and mixed-sex siblings in Kenya.

PMID- 1357345
TI  - Mortality and morbidity after high titre measles vaccine in Mexico.

PMID- 1357346
TI  - Role of glucose and insulin resistance in development of type 2 diabetes
      mellitus: results of a 25-year follow-up study.
AB  - Type 2 diabetes mellitus is characterised by resistance of peripheral tissues to
      insulin and a relative deficiency of insulin secretion. To find out which is the
      earliest or primary determinant of disease, we used a minimum model of glucose
      disposal and insulin secretion based on intravenous glucose tolerance tests to
      estimate insulin sensitivity (SI), glucose effectiveness (ie, insulin-independent
      glucose removal rate, SG), and first-phase and second-phase beta-cell
      responsiveness in normoglycaemic offspring of couples who both had type 2
      diabetes. 155 subjects from 86 families were followed-up for 6-25 years. More
      than 10 years before the development of diabetes, subjects who developed the
      disease had lower values of both SI (mean 3.2 [SD 2.4] vs 8.1 [6.7] 10(-3) I min
      1 pmol-1 insulin; p < 0.0001) and SG (1.6 [0.9] vs 2.3 [1.2] 10(-2) min-1, p <
      0.0001) than did those who remained normoglycaemic). For the subjects with both
      SI and SG below the group median, the cumulative incidence of type 2 diabetes
      during the 25 years was 76% (95% confidence interval 54-99). By contrast, no
      subject with both SI and SG above the median developed the disease. Subjects with
      low SI/high SG or high SI/low SG had intermediate risks. Insulin secretion,
      especially first phase, tended to be increased rather than decreased in this
      prediabetic phase and was appropriate for the level of insulin resistance. The
      development of type 2 diabetes is preceded by and predicted by defects in both
      insulin-dependent and insulin-independent glucose uptake; the defects are
      detectable when the patients are normoglycaemic and in most cases more than a
      decade before diagnosis of disease.

PMID- 1357347
TI  - Effect of Helicobacter pylori on gastric somatostatin in duodenal ulcer disease.
AB  - Infection of the gastric antrum by Helicobacter pylori is associated with
      recurrent duodenal ulcer disease but the mechanism of ulcerogenesis is unclear.
      Since pathways inhibiting gastric secretion are defective in patients with
      duodenal ulcers, we investigated whether H pylori interferes with the normal
      gastric inhibition that is mediated by somatostatin. We studied 28 patients with
      active duodenal ulcers in whom H pylori was eradicated successfully. In 18
      patients, we measured the density of antral somatostatin-immunoreactive cells and
      in a further 10 subjects, the amount of somatostatin mRNA before and after
      eradication of H pylori was determined. After eradication, the median density of
      somatostatin-immunoreactive cells increased significantly from 9 (range 3-47) to
      19 (6-57) cells per mm muscularis mucosa (p = 0.025). The median somatostatin
      mRNA/rRNA ratio increased from 50 (25-160) to 95 (40-180) (p = 0.01). The number
      of gastrin cells and quantity of gastrin mRNA did not change significantly. Our
      results suggest that in duodenal ulcer disease, gastric secretory function is
      disinhibited through the suppression of mucosal somatostatin.

PMID- 1357348
TI  - Association of sleep-wake habits in older people with changes in output of
      circadian pacemaker.
AB  - Many elderly people complain of disturbed sleep patterns but there is not
      evidence that the need to sleep decreases with age; it seems rather that the
      timing and consolidation of sleep change. We tried to find out whether there is a
      concurrent change in the output of the circadian pacemaker with age. The phase
      and amplitude of the pacemaker's output were assessed by continuous measurement
      of the core body temperature during 40 h of sustained wakefulness under constant
      behavioural and environmental conditions. 27 young men (18-31 years) were
      compared with 21 older people (65-85 years; 11 men, 10 women); all were healthy
      and without sleep complaints. The mean amplitude of the endogenous circadian
      temperature oscillation (ECA) was 40% greater in young men than in the older
      group. Older men had a lower mean temperature ECA than older women. The minimum
      of the endogenous phase of the circadian temperature oscillation (ECP) occurred 1
      h 52 min earlier in the older than in the young group. Customary bedtimes and
      waketimes were also earlier in the older group, as was their daily alertness
      peak. There was a close correlation between habitual waketime and temperature ECP
      in young men, which may lose precision with age, especially among women. These
      findings provide evidence for systematic age-related changes in the output of the
      human circadian pacemaker. We suggest that these changes may underlie the common
      complaints of sleep disturbance among elderly people. These changes could reflect
      the observed age-related deterioration of the hypothalamic nuclei that drive
      mammalian circadian rhythms.

PMID- 1357349
TI  - Comparison of umbilical-artery velocimetry and cardiotocography for surveillance
      of small-for-gestational-age fetuses.
AB  - Intrauterine growth retardation is associated with an increased risk of fetal
      asphyxia as well as greater perinatal morbidity and mortality. Ultrasound
      fetometry enables detection of fetuses that are small for gestational age.
      Doppler velocimetry of the umbilical artery has good predictive ability for fetal
      distress, but it is not yet clear whether it could replace cardiotocography in
      antenatal surveillance of small-for-gestational-age fetuses. We have done a
      randomised comparison of the two methods. At four obstetric departments in
      Sweden, women with fetuses found to be small on ultrasound examination at 31
      completed weeks of pregnancy or later were randomly assigned to antenatal
      surveillance with either doppler velocimetry (doppler; 214) or cardiotocography
      (CTG; 212). Pregnancies in the doppler group were managed according to a protocol
      based on blood-flow classes deriving from the semiquantitative evaluation of
      umbilical-artery velocity waveforms; unless the pregnancy was complicated by any
      other disorder, no antenatal cardiotocography was done. By comparison with the
      CTG group, the doppler group had fewer monitoring occasions (mean 4.1 [SD 3.1] vs
      8.2 [6.2], p < 0.01), antenatal hospital admissions (68 [31.3%] vs 97 [45.8%], p
      < 0.01), inductions of labour (22 [10.3%] vs 46 [21.7%], p < 0.01), emergency
      caesarean sections for fetal distress (11 [5.1] vs 30 [14.2%], p < 0.01), and
      admissions to neonatal intensive care (76 [35.5%] vs 92 [43.4%], p = 0.10). The
      groups did not differ in gestational age at birth, birthweight, Apgar scores, or
      total number of caesarean deliveries. Umbilical-artery doppler velocimetry of
      small-for-gestational-age fetuses allows antenatal monitoring and obstetric
      interventions to be aimed more precisely than does cardiotocography.

PMID- 1357350
TI  - Efficacy of lignocaine analgesia during treatment to the cervix.
AB  - There is no consensus amongst physicians about the need for analgesia when a
      woman undergoes ablative therapy of the cervix. Many doctors believe that the
      discomfort felt during such procedures is insubstantial. By means of a randomised
      double-blind placebo-controlled trial, we have shown that patients experience
      considerable pain during cold-coagulation treatment of the cervix. We found that
      intracervical lignocaine leads to a significant (p < 0.01) reduction in this
      pain.

PMID- 1357351
TI  - PML: more neurological bad news for AIDS patients.

PMID- 1357352
TI  - Cross design synthesis: a new strategy for studying medical outcomes?

PMID- 1357353
TI  - South-east Asia in the twenty-first century.

PMID- 1357354
TI  - Malignant melanoma. Report of a meeting of physicians and scientists, University
      College London Medical School.

PMID- 1357355
TI  - Cladribine (2-chlorodeoxyadenosine)

PMID- 1357356
TI  - Medical curriculum and licensing: still in need of radical revision.

PMID- 1357357
TI  - 40 years of being treated for nocturnal enuresis.

PMID- 1357358
TI  - Stavudine.

PMID- 1357359
TI  - High concentrations of the interleukin-1 receptor antagonist in serum of patients
      with Hodgkin's disease.

PMID- 1357360
TI  - Association of HLA-DPB with Hodgkin's disease.

PMID- 1357361
TI  - Intralesional steroid injection after nerve-block in orofacial granulomatosis.

PMID- 1357362
TI  - Bromocriptine-induced acute hepatitis.

PMID- 1357363
TI  - Combined and alternating ganciclovir/foscarnet in HIV-related cytomegalovirus
      encephalitis.

PMID- 1357364
TI  - Uvula and oesophageal ulcerations with foscarnet.

PMID- 1357365
TI  - Possible role of Rochalimaea henselae in pathogenesis of AIDS encephalopathy.

PMID- 1357366
TI  - Clinically diagnosed AIDS cases without evident association with HIV type 1 and 2
      infections in Ghana.

PMID- 1357367
TI  - Prevention of cisplatin-induced emesis. The Italian Group for Antiemetic
      Research.

PMID- 1357368
TI  - Urticaria and angioedema induced by low-molecular-weight heparin.

PMID- 1357369
TI  - Hyperinsulinaemia and syndrome X.

PMID- 1357370
TI  - Hyperinsulinaemia and syndrome X.

PMID- 1357371
TI  - Shift in age in chickenpox.

PMID- 1357372
TI  - Method to increase the sensitivity of poliovirus isolation.

PMID- 1357373
TI  - Needlestick injuries.

PMID- 1357374
TI  - Needlestick injuries.

PMID- 1357375
TI  - Prophylactic vancomycin in very-low-birthweight infants.

PMID- 1357376
TI  - The final autonomy.

PMID- 1357377
TI  - The final autonomy.

PMID- 1357378
TI  - The final autonomy.

PMID- 1357379
TI  - Blood donation.

PMID- 1357380
TI  - Blood donation.

PMID- 1357381
TI  - Can you make a bottle?

PMID- 1357382
TI  - Treatment of hypophosphataemia.

PMID- 1357383
TI  - Vincristine for thrombotic thrombocytopenic purpura.

PMID- 1357384
TI  - Neurofibrillary tangles and senile plaques in brain of elderly leprosy patients.

PMID- 1357385
TI  - IgG2 deficiency in patients with hypergammaglobulinaemia.

PMID- 1357386
TI  - IgG2 deficiency in patients with hypergammaglobulinaemia.

PMID- 1357387
TI  - Simvastatin during warfarin therapy in hyperlipoproteinaemia.

PMID- 1357388
TI  - Mumps vaccines and meningitis.

PMID- 1357389
TI  - Heterogeneous mumps vaccine.

PMID- 1357390
TI  - Melanocyte transplantation in vitiligo.

PMID- 1357391
TI  - Unusually severe course of tetanus in a vaccinated child with sickle cell
      disease.

PMID- 1357392
TI  - Early antimicrobial treatment of dilated cardiomyopathy associated with Borrelia
      burgdorferi.

PMID- 1357393
TI  - African tick-bite fever: a new spotted fever group rickettsiosis under an old
      name.

PMID- 1357394
TI  - Pregnancy after induction of ovulation with recombinant human FSH in polycystic
      ovary syndrome.

PMID- 1357395
TI  - Simple method for cystic fibrosis carrier screening.

PMID- 1357396
TI  - Cystic fibrosis mice with disease-related changes in lung and reproductive tract.

PMID- 1357397
TI  - Screening for cystic fibrosis carriers.

PMID- 1357398
TI  - Adult Schonlein-Henoch purpura after lisinopril.

PMID- 1357399
TI  - Intraportal 5-fluorouracil for colorectal cancer: the AXIS trial.

PMID- 1357400
TI  - Transmission of de-novo mutation associated with facioscapulohumeral muscular
      dystrophy.

PMID- 1357401
TI  - Dog days and antiandrogens.

PMID- 1357402
TI  - Intravenous immunoglobulins and hepatitis C transmission in healthy pregnant
      women.

PMID- 1357405
TI  - Screening for fetal malformations.

PMID- 1357404
TI  - Provocation paralysis.

PMID- 1357403
TI  - Endogenous benzodiazepine receptor ligands in idiopathic recurring stupor.
AB  - "Endozepines" are endogenous ligands for the benzodiazepine recognition sites on
      gamma-aminobutyric acid A receptors in the nervous system. Idiopathic recurring
      stupor (IRS) is a syndrome of spontaneous stupor or coma that is not associated
      with known metabolic, toxic, or structural abnormalities but can be reversed by
      flumazenil, a pure benzodiazepine antagonist. We measured endozepine-2 and
      endozepine-4 by high-performance liquid chromatography and radioreceptor assay in
      serum and cerebrospinal fluid from three patients with IRS. During episodes of
      stupor there was a large (up to 300-fold compared with control patients) increase
      of endozepine-4 content in cerebrospinal fluid and serum, but a return to normal
      concentrations between attacks. Endozepine-4 may contribute to, or be the cause
      of, IRS. The reasons for abnormal concentrations of endozepine in blood and brain
      are unknown.

PMID- 1357406
TI  - Expressed emotion in schizophrenia.

PMID- 1357407
TI  - Cerebral resection for intractable epilepsy: long-term effects.

PMID- 1357408
TI  - Doctors to be: kingdom or exile?

PMID- 1357409
TI  - Air pollution and infant mortality in the Czech Republic, 1986-88.
AB  - An ecological study of infant mortality and air pollution was conducted in the
      Czech Republic. Routinely collected data on infant mortality and air pollution in
      the period 1986-88 were analysed for the 46 of the 85 districts in the republic
      for which both were available. The independent effects of total suspended
      particulates (TSP-10), sulphur dioxide (SO2), and oxides of nitrogen (NOx)
      adjusted for district socioeconomic characteristics, such as income, car
      ownership, and abortion rate, were estimated by logistic regression. We found
      weak positive associations between neonatal mortality and quintile of TSP-10 and
      SO2. Stronger adjusted effects were seen for postneonatal mortality, with a
      consistent increase in risk from the lowest to the highest TSP-10 quintile (p <
      0.001). Weaker and less consistent evidence of a positive association with NOx (p
      = 0.061) was observed. The strongest effects were seen for postneonatal
      respiratory mortality, which increased consistently from lowest to highest TSP-10
      quintile (p = 0.013). There was also a suggestion of a positive association with
      SO2 (p = 0.062). The highest to lowest quintile risk ratios for postneonatal
      respiratory mortality were 2.41 (95% Cl 1.10-5.28) for TSP-10, 3.91 (0.90-16.9)
      for SO2, and 1.20 (0.37-3.91) NOx. The specificity of the association between air
      pollution quintile (especially TSP-10) and postneonatal respiratory mortality is
      consistent with the known effects of air pollution on respiratory disease
      morbidity in children. These ecological associations require confirmation in an
      individually based study.

PMID- 1357410
TI  - Evidence of prenatal influences on breast cancer risk.
AB  - Intrauterine exposure to high concentrations of endogenous pregnancy oestrogens
      may be important in the aetiology of breast cancer. In a nested case-control
      study we have assessed the relation between breast cancer risk and indicators of
      pregnancy oestrogen concentrations; pre-eclampsia/eclampsia is negatively related
      and measures of fetal size are positively related to oestrogen concentrations.
      Standard records for women born at Uppsala University Hospital between 1874 and
      1954 were linked with records of invasive breast cancer cases, identified through
      their unique national registration numbers in the Swedish Cancer Registry during
      1958-90. For each breast cancer case, we selected as potential controls female
      offspring of the first three mothers admitted to the hospital after the case's
      mother; only controls still living in Sweden and free from breast cancer when it
      was diagnosed in the case were finally included. Conditional logistic regression
      analysis was done for 458 breast cancer cases and 1197 matched controls. Pre
      eclampsia/eclampsia was associated with a breast cancer rate ratio of 0.24 (95%
      confidence interval 0.09-0.70, p = 0.01). Linear trends for breast cancer
      incidence with increasing birth weight, birth length, and placental weight were
      positive but not significant. Thus, prenatal factors are important in breast
      carcinogenesis. Concentrations of pregnancy oestrogens may be one such factor,
      but other prenatal or perinatal factors cannot be excluded.

PMID- 1357411
TI  - The Leicester anti-vaccination movement.

PMID- 1357413
TI  - Europe and the big "C".

PMID- 1357412
TI  - Might efforts to increase birthweight in undernourished women do more harm than
      good?

PMID- 1357414
TI  - Compulsory intervention during pregnancy.

PMID- 1357415
TI  - Health and environment.

PMID- 1357416
TI  - First trimester prenatal diagnosis of trisomy 21 in fetal cells from maternal
      blood.

PMID- 1357417
TI  - Safety of chorionic villus sampling.

PMID- 1357418
TI  - Screening for Down's syndrome.

PMID- 1357419
TI  - Intravenous fetal transfusion of immunoglobulin for alloimmune thrombocytopenia.

PMID- 1357420
TI  - Germline APC mutation familial adenomatous polyposis in Indian family.

PMID- 1357421
TI  - Resistance to fluoroquinolones in Salmonella non-typhi and Campylobacter spp.

PMID- 1357422
TI  - Susceptibility of endocarditis streptococci to clindamycin.

PMID- 1357423
TI  - Pneumococcal immunisation and the healthy elderly.

PMID- 1357424
TI  - Assessment of Crohn's disease activity and alpha 1-antitrypsin in faeces.

PMID- 1357425
TI  - Eltoprazine in mentally retarded self-injuring patients.

PMID- 1357426
TI  - Psychiatric aspects of loin pain/haematuria syndrome.

PMID- 1357427
TI  - Nitric oxide during hand ventilation in patient with acute respiratory failure.

PMID- 1357428
TI  - Atheroembolism in HIV-positive individuals.

PMID- 1357429
TI  - Topical trifluridine for mucocutaneous acyclovir-resistant herpes simplex II in
      AIDS patient.

PMID- 1357430
TI  - Acceptability of screening for HIV seroprevalence in women with cervical
      pathology.

PMID- 1357431
TI  - Is routine p24 HIV antigen screening justified in Thai blood donors?

PMID- 1357432
TI  - Recall of therapeutic devices in Australia.

PMID- 1357433
TI  - Reduction of deaths after drug labelling for risk of Reye's syndrome.

PMID- 1357434
TI  - Maasai diet.

PMID- 1357435
TI  - Availability of information about AIDS.

PMID- 1357436
TI  - Reporting side-effects.

PMID- 1357437
TI  - Transmission of HIV-associated tuberculosis to health-care workers.

PMID- 1357438
TI  - Combined oestrogen-progestogen replacement and breast cancer risk.

PMID- 1357439
TI  - Indomethacin, ranitidine, and interleukin-2 in melanoma.

PMID- 1357440
TI  - Bone marrow transplantation for high-risk childhood lymphoblastic leukaemia.

PMID- 1357441
TI  - Paradoxical pain.

PMID- 1357442
TI  - Cytomegalovirus encephalitis in four immunocompetent patients.

PMID- 1357443
TI  - Postoperative hypoxia: an indication for intermittent hyperbaric oxygen?

PMID- 1357444
TI  - Prophylactic vancomycin for very-low-birthweight infants.

PMID- 1357445
TI  - Prevalence of specific antibodies to Chlamydia pneumoniae (TWAR) in Swedish
      orienteers.

PMID- 1357446
TI  - Lover's arm.

PMID- 1357447
TI  - Serum cardiac troponin T after extraordinary endurance exercise.

PMID- 1357448
TI  - Breast cancer survival among women under age 50: is mammography detrimental?
AB  - Great uncertainty exists about the benefit of detecting breast cancer by
      mammography in women under 50 years of age. We have reviewed the survival of
      patients aged 49 years or less whose cancers were detected by mammography alone.
      117 women under the age of 50 years were diagnosed with breast cancer between
      1978 and 1991 based only on an abnormal mammogram. Ductal carcinoma in-situ
      (DCIS) was found in 47 (40%) of these women, whilst 70 (60%) had infiltrating
      ductal or infiltrating lobular carcinomas. During the same interval, 928 women in
      this age group presented with palpable breast cancer. DCIS was diagnosed in 82
      (9%) of these women, whilst 846 (91%) had infiltrating carcinoma. Among the
      infiltrating cancers detected by mammography alone, 50% were stage I, whilst only
      30% of the women with palpable cancers were stage I. Five-year survival for all
      mammographically detected cancer patients was 95%, whereas for women with
      palpable cancers the survival was 74% (p < 0.00005). If DCIS is not included, the
      corresponding survivals are 91% for mammographically detected infiltrating
      cancers and 72% for palpable infiltrating cancers. Only 1 woman who died among
      those with palpable cancer had had a mammogram before diagnosis. Our data
      contradict the suggestion that women under 50 are put at a survival disadvantage
      by undergoing mammography. We believe that investigators who have reported
      negative results in this age group must examine other causes for their results.

PMID- 1357449
TI  - Serum cholesterol, triglycerides, and aggression in the general population.
AB  - A higher than expected number of violent deaths and suicides in coronary
      prevention trials has provoked interest in the possibility that low serum
      cholesterol concentrations are associated in the general population with
      personality characteristics predisposing to aggressive and suicidal behaviour. We
      have investigated this possibility in the Edinburgh Artery Study. We measured
      serum lipid concentrations in blood samples taken from fasting subjects and
      assessed personality characteristics on the Bedford Foulds Personality Deviance
      Scales in a random sample of 1592 men and women aged 55-74 years, selected from
      age-sex registers of ten general practices in Edinburgh. Serum cholesterol
      concentration was not significantly associated with aggression in men, but it was
      associated in multivariate analysis (though not univariate analysis) with
      denigratory attitudes towards others among women. However, serum triglyceride
      concentration was related, especially in men, to hostile acts (r = 0.13, p <
      0.001) and domineering attitude (r = 0.12, p < 0.001) independently of age, total
      and HDL cholesterol, cigarette smoking, and alcohol consumption. Subjects taking
      part in prevention trials have higher triglyceride concentrations than the
      general population and the relation between serum triglyceride concentration and
      aggression merits further investigation.

PMID- 1357450
TI  - Coronary revascularisation in insulin-dependent diabetic patients with chronic
      renal failure.
AB  - Insulin-dependent diabetic patients found to have substantial coronary artery
      disease at the time of assessment for renal transplantation have 2-year survival
      of less than 50%. Because most of these patients have no angina symptoms their
      management is controversial. We tried to find out whether coronary artery
      revascularisation in such patients might decrease the combined incidence of
      unstable angina, myocardial infarction, and cardiac death. 151 consecutive
      insulin-dependent diabetic candidates for renal transplantation underwent
      coronary angiography. 31 had stenoses greater than 75% in one or more coronary
      arteries, atypical chest pain or no chest pain, and a left ventricular ejection
      fraction greater than 0.35. Of these, 26 agreed to be randomly assigned medical
      treatment (a calcium-channel-blocking drug plus aspirin) or revascularisation
      (angioplasty or coronary bypass surgery). 10 of 13 medically managed and 2 of 13
      revascularised patients had a cardiovascular endpoint within a median of 8.4
      months of coronary angiography (p < 0.01). 4 medically managed patients died of
      myocardial infarction during follow-up. Thus, revascularisation decreased the
      frequency of cardiac events in insulin-dependent diabetic patients with chronic
      renal failure and symptomless coronary artery stenoses. These findings suggest
      that diabetic renal transplant candidates should be screened for silent coronary
      artery disease, because revascularisation may decrease cardiac morbidity and
      mortality in this population.

PMID- 1357451
TI  - Randomised, placebo-controlled multicentre trial of clodronate in multiple
      myeloma. Finnish Leukaemia Group.
AB  - Osteolytic lesions and pathological fractures are common in multiple myeloma.
      Because clodronate inhibits osteoclastic resorption, we did a randomised,
      controlled trial in 350 patients from 23 hospitals. All patients received
      standard melphalan-prednisolone, and were randomised to receive clodronate 2.4 g
      daily or placebo for 24 months. The proportion of patients with progression of
      osteolytic bone lesions was twice as high in the placebo group (n = 168 at
      baseline) than in the clodronate group (n = 168 at baseline) in an intention-to
      treat analysis (24 vs 12%, p = 0.026). Progression of vertebral fractures was
      lower in the clodronate group, but the difference was not significant (30 vs
      40%). Serum calcium and urinary calcium excretion decreased significantly in both
      groups, but the changes were greater in the clodronate group. The percentage of
      patients feeling no pain increased more in the clodronate group (from 24 to 54%,
      p < 0.001) than in the placebo group (from 29 to 44%, p < 0.01). Side-effects
      were similar in both groups. We conclude that clodronate is an effective and safe
      adjunct in the management of multiple myeloma. The drug delays osteolytic bone
      lesions, reduces the degree of hypercalcaemia and hypercalciuria, and decreases
      pain.

PMID- 1357452
TI  - Significance of CD44 gene products for cancer diagnosis and disease evaluation.
AB  - With increasing emphasis on the early detection of cancer, the search is on for
      reliable markers that will be clinically helpful in the diagnosis of small
      tumours and in the assessment of their metastatic potential. This report presents
      evidence that an abnormal pattern of activity of the CD44 gene is a promising
      candidate for both of these purposes in various types of malignancy. By a
      mechanism known as alternative splicing this gene can produce different messenger
      RNA molecules (transcripts) which are detectable, after amplification, as
      separate bands in electrophoretic gels. In neoplasia many abnormal variant
      transcripts are produced. A previous finding in animal experiments, that one such
      variant might be important in metastasis, prompted our study of human tumour
      tissue, benign and malignant, and of corresponding normal tissues. We studied
      tumour tissue from 34 patients with neoplastic disease (mostly breast or colon
      cancer) and normal or non-malignant diseased breast or colonic tissue from 11
      patients and peripheral blood leucocytes from 4 healthy volunteers. CD44 gene
      activity was studied by amplifying messenger RNA with the polymerase chain
      reaction (PCR) followed by electrophoresis and blot hybridisation. In malignant
      tissues there was gross overproduction of each of 9 or more alternatively-spliced
      large molecular variants in all samples, whereas in the control samples only the
      standard product was routinely detected with occasional minimal quantities of one
      or two small variants. Furthermore, the band pattern permitted differentiation
      between the 23 cases with metastatic tumours of the breast or colon and the 8
      with no detectable metastases. Calibration studies seeding blood with tumour
      cells showed that the technique can detect as few as 10 tumour cells among 10(7)
      leucocytes (1 ml of blood). Analysis of CD44 splice variants may prove to have
      applications not just to the early detection of metastatic potential in surgical
      biopsy specimens but also, if our findings are confirmed, in readily available
      bodily fluids, to the early diagnosis of cancer in screening programmes, to the
      assessment of remaining disease in the body and to the early detection of
      recurrences.

PMID- 1357453
TI  - Continuous intravenous famotidine for haemorrhage from peptic ulcer.
AB  - Peptic ulcer bleeding often stops spontaneously but rebleeding may be
      catastrophic. Emergency surgery carries risks so safe medical therapies are
      needed. Since platelet function and plasma coagulation are both pH sensitive and
      since pepsin lyses clot at low pH the maintenance of gastric pH close to
      neutrality might influence rebleeding rates. Previous trials with H2 antagonists
      have been inadequate although a 1985 meta-analysis did support an important
      clinical effect. We report here a large multicentre trial of famotidine in ulcer
      bleeding. 1005 patients admitted to one of sixty-seven hospitals in the UK or
      Eire with haemorrhage from peptic ulcer with endoscopic signs of oozing, black
      slough, fresh clot or visible vessel were randomly allocated to famotidine (10 mg
      bolus followed by 3.2 mg/h intravenously) or matching placebo for 72 h. This
      famotidine regimen had previously been shown to maintain pH near 7 in such
      patients. 497 patients received famotidine and 508 placebo. The treatment groups
      were similar in respect of age, sex, ulcer site, and signs and severity of
      bleeding. Case fatality (6.2% famotidine vs 5.0% placebo), rebleeding (23.9% vs
      25.5% placebo), and surgery (15.5% vs 17.1% placebo) rates were not significantly
      different between the two groups. This trial suggests that potent inhibition of
      gastric secretion does not influence the natural history of peptic ulcer
      haemorrhage.

PMID- 1357454
TI  - Transcatheter occlusion of persistent arterial duct. Report of The European
      Registry.
AB  - Rashkind's "double umbrella" technique for percutaneous transcatheter occlusion
      of patent arterial duct (ductus arteriosus) has been used successfully in several
      centres. To assess its feasibility, safety, and efficacy in routine clinical
      practice, a European registry was established. In 642 of 686 patients entered
      into the study, the device was successfully implanted at the first attempt, and
      in a further 9 at a subsequent attempt. 491 patients (71% of all patients
      entered) had doppler-echocardiographic evidence of complete occlusion with a
      single device at the latest follow-up. Kaplan-Meier survival estimates indicated
      a complete occlusion rate of 82.5% (95% Cl 79.4 to 85.8) at one year after
      implantation of a single device. A second device was implanted in 41 patients
      with residual flow, and 37 of these had complete occlusion, giving an overall
      latest follow-up occlusion rate of 77% and an actuarial complete occlusion rate
      for one or two devices of 94.8% (95% Cl 92.9 to 96.7) at 30 months after
      implantation of the first device. 2 early deaths occurred (0.3%), both in
      patients with associated ventricular septal defect. Complications included
      embolisation of the device in 18 patients (2.4%), of whom 6 underwent catheter
      retrieval of the device. Mechanical haemolysis occurred in a further 4 patients
      (0.5%). Transcatheter occlusion of the arterial duct is a safe and effective
      alternative to surgical closure. A second device is sometimes needed to achieve
      complete occlusion.

PMID- 1357455
TI  - Factor VIII gene explains all cases of haemophilia A.
AB  - Using an mRNA-based method to examine haemophilia A mutations we provide an
      explanation for the puzzling report that half of the mutations causing severe
      disease are not detected by analysis of the putative promoter, exons, and most
      exon/intron boundaries of the factor VIII gene. An unusual cluster of mutations
      involving regions of intron 22 not examined earlier leads to defective joining of
      exons 22 and 23 in the mRNA and caused haemophilia A in 10/24 severely affected
      UK patients.

PMID- 1357456
TI  - Fatal myocardial infarction and use of psychotropic drugs in young women.
AB  - We have observed an unexpected 17-fold increase in risk of fatal [corrected]
      myocardial infarction (relative risk 16.9, 95% confidence interval 3.9-72.8)
      associated with current use of psychotropic drugs. This incidental finding, in a
      case-control study of cardiovascular mortality in women aged 16-39 not designed
      to test any hypothesis about psychotropic drugs, should be treated cautiously.
      There is, however, evidence of a relation between psychiatric morbidity and
      cardiovascular disease and the association recorded here requires further
      investigation.

PMID- 1357457
TI  - Psychotropic drugs and myocardial infarction: cause for or caused by panic?

PMID- 1357458
TI  - London's medicine.

PMID- 1357459
TI  - Nosocomial infection with respiratory syncytial virus.

PMID- 1357460
TI  - Endometriosis: time for reappraisal.

PMID- 1357461
TI  - Protective efficacy of a serogroup B meningococcal vaccine in Sao Paulo, Brazil.
AB  - Serogroup B Neisseria meningitidis is the most common cause of epidemic
      meningococcal disease in developed countries. Until recently no vaccine has been
      available for prevention of infection with this organism. In an attempt to
      control epidemic serogroup B meningococcal disease in greater Sao Paulo, Brazil,
      during 1989 and 1990, a Cuban-produced outer-membrane-protein-based serogroup B
      meningococcal vaccine was given to about 2.4 million children aged from 3 months
      to 6 years. We have done a case-control study to estimate the efficacy of the
      vaccine in greater Sao Paulo. Microbiologically confirmed cases of serogroup B
      meningococcal disease were identified through hospital-based surveillance.
      Controls were matched by neighbourhood and age. Vaccination status was confirmed
      by inspection of vaccination cards. Between June, 1990, and June, 1991, 112
      patients and 409 matched controls with confirmed vaccine status were enrolled.
      Estimated vaccine efficacy varied by age: 48 months or older = 74% (95% Cl 16 to
      92%), 24 to 47 months = 47% (-72 to 84%), and less than 24 months = -37% (< -100
      to 73%). Our results suggest that the Cuban-produced vaccine may be effective for
      prevention of serogroup B meningococcal disease in older children and adults.

PMID- 1357462
TI  - Prospective controlled study of four infection-control procedures to prevent
      nosocomial infection with respiratory syncytial virus.
AB  - To determine the most effective infection control procedure in preventing
      nosocomial infection with respiratory syncytial virus (RSV), we did a prospective
      controlled study of four infection-control strategies in four wards in a large
      paediatric hospital in the west of Scotland. All children under two years old
      admitted to four general wards during three winter RSV epidemics (1989-92) were
      screened for RSV infection (by nasopharyngeal aspirate and direct
      immunofluorescence) within 18 hours of admission. The main outcome measure was
      the occurrence of nosocomial infection, defined as the number of children
      initially RSV negative who became RSV positive 7 days or more after hospital
      admission (incubation period for RSV infection is 5-8 days). Without special
      precautions, there was a high rate of nosocomial RSV infection (26%). Nosocomial
      infection was significantly reduced by the combination of cohort nursing with the
      wearing of gowns and gloves for all contacts of RSV-infected children (p =
      0.0022). Neither the use of gowns and gloves alone nor cohort nursing alone
      produced a significant reduction in cross-infection. In the final year, general
      clinical use of a policy of cohort nursing with gowns and gloves resulted in a
      reduction in the cross-infection rate by two-thirds of its original value (9.5%
      vs 26%). Combined with rapid laboratory diagnosis, cohort nursing and the wearing
      of gowns and gloves for all contacts with RSV-infected children can significantly
      reduce the risk of nosocomial RSV infection.

PMID- 1357464
TI  - Health-care spending--up, up, and away.

PMID- 1357463
TI  - A right to reproduce?

PMID- 1357465
TI  - France: prison sentences for doctors.

PMID- 1357466
TI  - USA: NIH reopens the Kemron case.

PMID- 1357467
TI  - USA: objections to protective respirators.

PMID- 1357468
TI  - Belarus: rebuilding communities after Chernobyl.

PMID- 1357469
TI  - Russia: dispute over extent of HIV infection.

PMID- 1357470
TI  - Another milestone in the human genome race.

PMID- 1357471
TI  - Poliovaccine and AIDS origin link very unlikely.

PMID- 1357472
TI  - Infant brain lipids and diet.

PMID- 1357473
TI  - Infant brain lipids and diet.

PMID- 1357474
TI  - Infant brain lipids and diet.

PMID- 1357475
TI  - Muscling in on salbutamol.

PMID- 1357476
TI  - Breastfeeding and HIV.

PMID- 1357477
TI  - Breastfeeding and HIV.

PMID- 1357478
TI  - Epilepsy, progressive cerebral calcifications, and coeliac disease.

PMID- 1357479
TI  - Smoking and suicide.

PMID- 1357480
TI  - Smoking and suicide.

PMID- 1357482
TI  - Smoking and suicide.

PMID- 1357481
TI  - Low cost anti-HCV screening of blood donors.

PMID- 1357483
TI  - Lack of improvement with ceftriaxone in motoneuron disease.

PMID- 1357484
TI  - Postoperative TPN-induced lactic acidosis.

PMID- 1357485
TI  - Heparin therapy and bone fractures.

PMID- 1357486
TI  - Immunoprophylaxis in cutaneous leishmaniasis.

PMID- 1357487
TI  - Co-trimoxazole versus dapsone-pyrimethamine for prevention of Pneumocystis
      carinii pneumonia.

PMID- 1357489
TI  - Positive lupus band test in cardiac myxoma.

PMID- 1357488
TI  - Levamisole treatment in HIV-infected Zambian children.

PMID- 1357491
TI  - Surgery for rectal cancer in Japan.

PMID- 1357490
TI  - Insulin resistance in retinal vein occlusion and glaucoma.

PMID- 1357492
TI  - MRC and research funding.

PMID- 1357493
TI  - MRC and research funding.

PMID- 1357494
TI  - Meta-analysis and multiple publication of clinical trial reports.

PMID- 1357495
TI  - Fibromyalgia: the Copenhagen declaration.

PMID- 1357496
TI  - Volunteering for research.

PMID- 1357497
TI  - Volunteering for research.

PMID- 1357498
TI  - Audit and research.

PMID- 1357499
TI  - "Blind" bronchoalveolar lavage.

PMID- 1357500
TI  - Carcinogenicity of 1,3-butadiene.

PMID- 1357501
TI  - Euthanasia.

PMID- 1357502
TI  - Thrombolysis with recombinant tissue-type plasminogen activator in renal venous
      thrombosis in infancy.

PMID- 1357503
TI  - Vancomycin-resistant Enterococcus durans.

PMID- 1357504
TI  - Splenic lymphoma with villous lymphocytes complicated by autoimmune haemolytic
      anaemia.

PMID- 1357505
TI  - Pre-pregnancy care in diabetes. The EASD Diabetic Pregnancy Study Group.

PMID- 1357506
TI  - Ondansetron and chest pain.

PMID- 1357507
TI  - Who should receive a 5-HT3 antagonist?

PMID- 1357508
TI  - Absence of local suppression in incestuous pregnancy.

PMID- 1357509
TI  - Rates of non-paternity.

PMID- 1357510
TI  - First singleton term birth after ovarian superovulation with rhFSH.

PMID- 1357511
TI  - Imposed upper airway obstruction in children.

PMID- 1357512
TI  - Ultrasound and fetal chromosome abnormalities.

PMID- 1357513
TI  - Blindness and myocardial infarction.

PMID- 1357514
TI  - Sumatriptan and recurrence of migraine.

PMID- 1357515
TI  - Sumatriptan and recurrence of migraine.

PMID- 1357517
TI  - Comparison of holmium and flashlamp pumped dye lasers for use in lithotripsy of
      biliary calculi.
AB  - The characteristics of laser lithotripsy of biliary calculi are compared for a
      flashlamp pumped dye laser (lambda = 640 nm) and a Cr:Tm:Ho-YAG laser (lambda =
      2.1 microns). Data on fragmentation efficiency with respect to laser power and
      pulse repetition rate are presented for different types of stones. It is shown
      that both lasers can produce effective stone fragmentation. The laser power
      required for efficient fragmentation characteristics is significantly less for
      the visible wavelength laser. However, the problems associated with damage to the
      fiber tips of the delivery system during operation were found to be less with the
      near infrared wavelength. The laser power for efficient fragmentation with the
      dye laser varies significantly for different types of stones while the power for
      efficient fragmentation with the holmium laser is the same for all stones.

PMID- 1357516
TI  - The role of guaifenesin in the treatment of sinonasal disease in patients
      infected with the human immunodeficiency virus (HIV).
AB  - Inflammatory sinonasal disease is a common problem in patients infected with the
      human immunodeficiency virus (HIV). Although some patients present with acute or
      chronic sinusitis, many describe persistent nasal congestion and thick, tenacious
      postnasal drainage, even in the absence of infection. The efficacy of guaifenesin
      as a mucolytic is poorly documented and support for its use in this setting is
      primarily anecdotal. This double-blind, placebo-controlled study assessed changes
      in nasal symptoms among 23 HIV-infected patients receiving either 3 weeks of
      guaifenesin (2400 mg daily) or placebo. The guaifenesin group reported less nasal
      congestion and thinner postnasal drainage compared to the placebo group and these
      differences were statistically significant (P < .05). Guaifenesin appears to be
      effective in managing HIV-infected patients with symptomatic rhinosinusitis and
      may be a useful adjunct for treating acute and chronic sinusitis in this
      population.

PMID- 1357518
TI  - Cell cycle dependent regulation of IMP dehydrogenase activity and effect of
      tiazofurin.
AB  - The activity of IMP dehydrogenase (IMP DH), the rate-limiting enzyme of de novo
      GTP biosynthesis, was shown to be increased in cancer cells. Tiazofurin, an
      inhibitor of IMP dehydrogenase, proved to be an effective agent in the treatment
      of refractory granulocytic leukemia. To examine the cell cycle dependent
      alterations of GTP synthesis and sensitivities to tiazofurin, we measured IMP DH
      activities and GTP pools, as well as the effects of tiazofurin on cell cycle
      phase enriched HL-60 cells. We now show that IMP DH activities and GTP
      concentrations are increased in S-phase enriched fractions of HL-60 cells.
      Moreover, the depletion of GTP concentrations by tiazofurin is most effective in
      S-phase enriched HL-60 cells. These results may be utilized in cancer
      chemotherapy to combine tiazofurin with biologic response modifiers which recruit
      quiescent leukemic cells into the cell cycle.

PMID- 1357519
TI  - Intraduodenal osmolality directly enhances insulin secretion in the rat.
AB  - To elucidate the direct effect of an intestinal osmolality on insulin release, we
      investigated the insulin response to intra-duodenal infusion of mannitol in rats.
      After the anesthesia with intraperitoneal pentobarbital sodium, one milliliter of
      mannitol solution (10% or 20%) was infused into the duodenum. Portal and femoral
      blood insulin concentrations significantly increased at 30, 60, and 120 min after
      intra-duodenal infusion of mannitol, although the blood glucose level did not
      change. Subcutaneous pre-administration of propranolol (0.4mg/kg) or metoprolol
      (25mg/kg) completely abolished this phenomenon. These results suggest that
      intestinal osmolality can directly enhance insulin secretion and that beta 1
      adrenergic mechanism is involved in this phenomenon.

PMID- 1357520
TI  - Manipulation of dopamine receptors alters hypoxic pulmonary vasoconstriction in
      isolated perfused rat lungs.
AB  - Using an isolated, perfused rat lung model, we examined the hypoxic pulmonary
      vasoconstriction (HPV). We studied the alterations in HPV induced by the
      selective DA1 receptor agonist, fenoldopam, the selective DA1 antagonist, SCH
      23390, as well as a combination of these agents. Fenoldopam significantly
      attenuated HPV. SCH 23390 had no effect on HPV, but was ableto block the effect
      of fenoldopam. These data confirm the presence of vasodilatory DA1 receptors in
      the pulmonary vascular bed. The data further suggest that ongoing DA1 activity
      may be important in counterbalancing some pathologic pulmonary hypertensive
      states.

PMID- 1357521
TI  - Somatostatin in Alzheimer's disease and depression.
AB  - Somatostatin (somatotropin release-inhibiting factor, SRIF) was originally
      discovered (1) during the purification of growth hormone-releasing factor from
      rat hypothalamus and was subsequently isolated and characterized (2) in 1972 from
      ovine hypothalamus. Since its initial characterization, SRIF has been shown to
      fulfill criteria for a neurotransmitter and to directly modulate neuronal
      activity as well as acting as an inhibitory factor regulating endocrine and
      exocrine secretion. Alterations in cerebrospinal fluid (CSF) concentrations of
      SRIF have been reported in several diseases exhibiting prominent cognitive
      dysfunction, including Alzheimer's disease (AD), major depression, Huntington's
      chorea, multiple sclerosis, schizophrenia and Parkinson's disease, while evidence
      for regional brain tissue concentration deficits in SRIF are more specific for
      AD. This mini-review will focus on the studies reporting alterations in CSF and
      postmortem tissue concentrations of SRIF in AD and depression.

PMID- 1357522
TI  - P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary
      endothelial cells.
AB  - The expression of a functional P-glycoprotein (P-gp) which pumps drugs out of
      brain capillary endothelial cells (BCEC) into blood was studied by evaluating the
      steady-state uptake and efflux of vincristine (VCR) by primary cultured bovine
      BCEC. The steady-state uptake of VCR was increased in the presence of metabolic
      inhibitors, and an anti-P-gp monoclonal antibody, MRK16, as well as verapamil and
      steroid hormones which are known to reverse multidrug resistance in tumor cells.
      Furthermore, efflux of VCR from BCEC was inhibited by verapamil. By
      immunohistochemistry, P-gp was localized at the luminal side of the capillary
      endothelial cells in both gray matter of bovine brain and primary cultured BCEC.
      These data suggest that P-gp functions as a drug efflux pump at the luminal side
      of BCEC and regulates the transfer of certain lipophilic drugs from the blood
      into the brain.

PMID- 1357523
TI  - HS-142-1, a novel polysaccharide of microbial origin, specifically recognizes
      guanylyl cyclase-linked ANP receptor in rat glomeruli.
AB  - HS-142-1, a novel polysaccharide, of microbial origin had been characterized as a
      specific antagonist of guanylyl cyclase-linked atrial natriuretic peptide (ANP)
      receptors (ANP-GC receptor) in bovine adrenal cortex. The effect of HS-142-1 on
      ANP receptors of rat glomeruli were examined. HS-142-1 blocked rat ANP (r-ANP)
      stimulated cGMP production in a concentration-dependent manner, although it
      caused only slight inhibition in the specific binding of [125I]-rANP to the
      glomeruli where only a small portion of the binding sites are coupled to guanylyl
      cyclase. HS-142-1 recognized the 135K ANP receptor which is thought to be ANP-GC
      receptors but did not recognized 60K receptor, guanylyl cyclase-free type from
      affinity cross-linking studies with glomerular membranes. These results indicate
      that HS-142-1 is a specific antagonist for the ANP-GC receptor in rat glomeruli,
      and that it will be a powerful tool for understanding the physiological roles of
      ANP in renal responses.

PMID- 1357524
TI  - [Report on the 6th International Conference on acquired immunodeficiency syndrome
      (AIDS) (Dakar from 16 to 19 December, 1991)].

PMID- 1357525
TI  - Molecular characterization of pcp, the structural gene encoding the pyrrolidone
      carboxylyl peptidase from Streptococcus pyogenes.
AB  - This paper describes the cloning of a gene (pcp) coding for pyrrolidone
      carboxylyl peptidase (PYRase), an enzyme which selectively removes N-terminal
      pyroglutamic acid residues from polypeptides. This gene was isolated from
      Streptococcus pyogenes by construction of a gene library with a bacteriophage
      lambda-derived cosmid-Escherichia coli host system. Nucleotide sequence
      determination of a 1.3 kb restriction fragment revealed a 645 bp open reading
      frame encoding a 215-amino-acid product of M(r) 23,135 consistent with the 26 kDa
      polypeptide obtained from in vivo overexpression in E. coli. Southern
      hybridization confirmed that pcp is a single-copy gene on the S. pyogenes
      chromosome. 5' and 3' endpoint mapping of the 0.7 kb specific transcript observed
      by Northern analysis permitted the identification of transcriptional initiation
      and termination signals. Structural features of the pcp gene product from S.
      pyogenes are discussed and compared with that from Bacillus subtilis. The lack of
      sequence identity with any other known protein or nucleotide sequence suggests
      that this enzyme belongs to a new class of peptidase.

PMID- 1357526
TI  - Horizontal gene transfer of the Escherichia coli pap and prs pili operons as a
      mechanism for the development of tissue-specific adhesive properties.
AB  - Escherichia coli strains bind to Gal alpha 1-4Gal-containing glycolipids via P
      pili-associated G-adhesins. Three functional classes of adhesins with different
      binding specificities are encoded by conserved G-alleles. We suggest that the
      Class I papG-allele of strain J96 is a novel acquisition possibly introduced via
      horizontal gene transfer into one of the two P pili gene clusters carried by this
      strain. Closely related strains in the ECOR collection of natural E. coli
      isolates carry either a Class II or a Class III G-adhesin. Data indicate that
      genetic exchanges involving either entire pap or prs gene clusters or individual
      pap/prs genes have occurred. We propose that the retention and spread of pap/prs
      DNA among E. coli is the result of selection pressure exerted by mammalian
      intestinal isoreceptors.

PMID- 1357527
TI  - Evidence for global regulatory control of pilus expression in Escherichia coli by
      Lrp and DNA methylation: model building based on analysis of pap.
AB  - Pyelonephritis-associated pilus (Pap) expression is regulated by a phase
      variation control mechanism involving PapB, Papl, catabolite activator protein
      (CAP), leucine-responsive regulatory protein (Lrp) and deoxyadenosine methylase
      (Dam). Lrp and Papl bind to a specific non-methylated pap regulatory DNA region
      containing the sequence 'GATC' and facilitate the formation of an active
      transcriptional complex. Evidence indicates that binding of Lrp and Papl to this
      region inhibits methylation of the GATC site by Dam. However, if this GATC site
      is first methylated by Dam, binding of Lrp and Papl is inhibited. These events
      lead to the formation of two different pap methylation states characteristic of
      active (ON) and inactive (OFF) pap transcription states. The fae (K88), daa
      (F1845) and sfa (S) pilus operons share conserved 'GATC-box' domains with pap and
      may be subject to a similar regulatory control mechanism involving Lrp and DNA
      methylation.

PMID- 1357528
TI  - The Crl protein activates cryptic genes for curli formation and fibronectin
      binding in Escherichia coli HB101.
AB  - Curli are thin, coiled, temperature-regulated fibres on fibronectin-binding
      Escherichia coli. The subunit protein of curli was highly homologous at its amino
      terminus to SEF-17, the subunit protein of thin, aggregative fimbriae of
      Salmonella enteritidis 27655 strain 3b, suggesting that these fibres form a novel
      class of surface organelles on enterobacteria. E. coli HB101 is non-curliated and
      unable to bind soluble, iodinated fibronectin. The phenotypically cryptic curlin
      subunit gene, csgA, in HB101 is transcriptionally activated by expressing the
      cytoplasmic Crl on a multicopy plasmid. Transcriptional activation of csgA by Crl
      was observed after growth at 26 degrees C but not at 37 degrees C, even though
      crl transcription was not thermoregulated. A deletion of the 39 carboxy-terminal
      residues abolished Crl activity, whereas a deletion of 10 residues at the C
      terminus did not, implying that a region between residue 93 and 122 in the 132
      amino-acid-residue large Crl protein is required for activating curli expression
      in E. coli HB101. crl is a normal housekeeping gene in E. coli and it is
      suggested that its gene product may either be a DNA-binding protein affecting
      chromatin structure as has been suggested for histone-like protein H1 or interact
      with specific regulatory protein(s) controlling transcription of genes required
      for curli formation and fibronectin binding.

PMID- 1357529
TI  - Insulin response of cultured islets from diabetic and nondiabetic BB rats.
AB  - This study examines the insulin response of pancreatic islets isolated from
      diabetic BB rats (BBD), nondiabetic BB rats (BBN), and Wistar rats to in vitro
      stimulation. After a 48-hour culture period, insulin release in response to
      glucose (17.8 mmol/L) either alone, with glucose-dependent insulinotropic
      polypeptide (GIP) +/- somatostatin (SS), or with Arg +/- SS was measured. A
      static incubation system was used. Insulin secretion from islets cultured in 4.4
      mmol/L glucose (basal) did not differ between BBN and BBD rats (0.50% +/- 0.08%,
      0.67% +/- 0.25% of total islet cell content [TCC], respectively). High glucose
      concentrations (17.8 mmol/L) stimulated a modest increase in insulin release from
      BBD and BBN islets (1.8% +/- 0.48% and 2.1% +/- 0.19% TCC, respectively). The
      addition of GIP (1 nmol/L) enhanced glucose-stimulated insulin secretion from BBN
      rat islets (2.9% +/- 0.42% TCC), but had no effect on BBD islets (2.04% +/- 0.57%
      TCC). Somatostatin (1 mumol/L) completely reversed the glucose- and/or GIP
      stimulated insulin secretion from both BBN and BBD rat islets to basal levels
      (0.42% +/- 0.043%, 0.42% +/- 0.09% TCC, respectively). Arg (1 mmol/L) enhanced
      glucose-stimulated insulin secretion in both groups, although the greatest
      response was elicited from BBD rat islets (8.4-fold v 3.2-fold). Experiments
      comparing BB rats with Wistar rats demonstrated significant differences in the
      glucose-stimulated (17.8 mmol/L) insulin response of the islets. Islets taken
      from BBN and BBD were less responsive to glucose than those from Wistar rats.
      However, islets from BBD rats were hyperresponsive to Arg when compared with
      islets from Wistar rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357530
TI  - Influence of nutritional factors on growth and hydrolytic enzyme production in
      Nocardia asteroides.
AB  - The growth and production of hydrolytic enzymes such as alpha-amylase, esterase
      and peroxidase as influenced by the type of media, carbon and nitrogen sources
      and C:N ratio were monitored in Nocardia asteroides at 37 degrees C. Sabouraud
      dextrose and the synthetic media yielded maximum growth compared with tryptic soy
      broth. Among the carbon sources (dextrose, fructose, sucrose, maltose, starch and
      citrate), monosaccharides supported maximum growth and induced higher alpha
      amylase activity but repressed the peroxidase activity. On the other hand, the
      disaccharides and starch produced less growth but induced maximum esterase and
      peroxidase activities. Glutamate among the nitrogen sources (nitrate, nitrite,
      ammonium, hydroxylamine, glutamate and casein) supported maximum growth.
      Glutamate, nitrate and casein induced alpha-amylase and esterase activities but
      suppressed peroxidase activity. Nitrite, ammonium and hydroxylamine stimulated
      peroxidase activity to the maximum but repressed alpha-amylase and esterase
      activities. Low, medium and high C:N ratios induced maximum peroxidase, esterase
      and alpha-amylase activities, respectively.

PMID- 1357531
TI  - Role of type 1 and type 3 fimbriae on the adherence and pathogenesis of
      Salmonella enteritidis in mice.
AB  - Through hemagglutination tests two isogenic strains of Salmonella enteritidis
      were shown to possess type 1 fimbriae (strain V) and type 1 and type 3 fimbriae
      (strain A). The two strains bound to human buccal and mouse small intestine
      epithelial cells. Strain A attached to the epithelial cells more readily and in
      larger numbers in comparison to strain V. Adherence of both strains were
      sensitive to the presence of D-mannose and pretreatment of the epithelial cells
      with tannic acid did not promote D-mannose resistant type binding of strain A S.
      enteritidis to human buccal and mouse small intestine epithelial cells.
      Furthermore, results from LD50 study indicated that, when the tests were carried
      out through oral inoculation of the mice the highly fimbriated stain A appeared
      to be more virulent. However, when the tests were carried out through
      intraperitoneal inoculation strain V was more virulent. These results indicate
      that adherence is a major contributing factor to the virulence of S. enteritidis
      and both type 1 and type 3 fimbriae contribute to this phenomenon.

PMID- 1357533
TI  - Survey of drug-related deaths in Victoria.
AB  - OBJECTIVE: To audit drug-related deaths to determine the types of agents causing
      death in Victoria and to identify possible strategies for prevention of deaths in
      future. DESIGN: Retrospective audit of Coroner's case records. SUBJECTS: All
      deaths reported to the Coroner during 14 months from 1 July 1989 to 31 August
      1990 in Victoria in which toxicological investigation was undertaken and drugs or
      poisons were detected and were believed to be a major cause of death. RESULTS: Of
      the 231 people who had drug-related deaths, 156 were males, 75 were females and
      the average age was 35.5 +/- 14 years. Heroin and morphine were judged to be the
      primary cause of death in 35% of subjects and methadone in a further 4.8%.
      Tricyclic antidepressants were responsible for 14% of deaths, with no deaths due
      solely to mianserin. Benzodiazepines were the prime cause of death in 6.5% of
      subjects, but were identified in 40%. Poisons and chemicals were involved in only
      3% of deaths. Prescription drugs were primarily responsible for 47% of deaths.
      Forty-eight per cent of deaths occurred in known injecting drug users and 42% of
      all subjects had a clear history of antecedent depression. Only one drug-related
      death was clearly accidental, that of a two-year-old child taking his parents'
      medications, but the mode of most deaths was not clear, and may not have been
      suicide. Most deaths occurred outside hospital, only 25 subjects reaching
      hospital alive. CONCLUSIONS: Barbiturates and chloral hydrate are no longer major
      causes of drug-related deaths, probably because of decreased availability. Some
      drug-related deaths, especially those related to tricyclic antidepressants, may
      be prevented if deaths and hospitalisations due to toxic substances are monitored
      and the availability and scheduling of toxic substances are regularly reviewed.

PMID- 1357532
TI  - Recognition of the self idiotype by T cells: induction of a rapid increase in
      cytoplasmic free calcium in T cells recognizing a variable L chain determinant.
AB  - To investigate the initial stages of recognition of the self idiotype (Id) by T
      cells, we examined the early increase in cytoplasmic free calcium ([Ca2+]i)
      occurring in murine CD4+ T cells specific for a model Id, Id315, following their
      interaction with the Id. The changes in [Ca2+]i were monitored with stopped-flow
      fluorometry by loading T cells with fura 2, a Ca(2+)-binding fluorescent dye. An
      increase of [Ca2+]i in the Id-specific T cell line was dependent on the presence
      of both antigen-presenting cells (APC) and Id315. When T cells were mixed with
      APC pulsed with M315 for 90 min at 37 C, a significant increase in T cell [Ca2+]i
      was observed within one second. A pronounced elevation in [Ca2+]i was also
      observed in T cells after their interaction with APC which had been pulsed for 90
      min with VL-315 Id-containing proteins (such as VL-315, L315, Fv-315 or Fab'-315
      fragments). In contrast, pulsing APC for 5 min with the VL fragment produced
      little or no change in the [Ca2+]i. These results suggest that VL must be further
      processed by APC before it can be recognized by T cells. Indeed, a synthetic VL
      region peptide (positions 91-108, designated as P18) produced an elevation in T
      cell [Ca2+]i when mixed with APC without pulsing.

PMID- 1357534
TI  - [Neurohumoral regulatory mechanisms in heart failure].

PMID- 1357535
TI  - The complete derived amino acid sequence of human lysyl oxidase and assignment of
      the gene to chromosome 5 (extensive sequence homology with the murine ras
      recision gene).
AB  - Lysyl oxidase catalyzes the oxidation of lysine residues to alpha-aminoadipic
      delta-semialdehyde. This is the first step in the covalent cross-linking of
      collagen and tropoelastin and results in the formation of insoluble collagen and
      elastic fibers in the extracellular matrix. We have characterized the complete
      nucleotide sequence of human lysyl oxidase (EC 1.4.3.13) and compared the derived
      amino acid sequence (417-amino acids) to rat lysyl oxidase and the mouse ras
      recision gene (rrg). 88% of amino acids and 83% of nucleotides were conserved
      between human and rat lysyl oxidase. The mouse ras recision gene demonstrated 89%
      conservation of amino acids with human lysyl oxidase. The sequence conservation
      was not evenly distributed along the molecule. The carboxy terminus of the
      protein, which contains the putative copper binding sites and is likely to be the
      catalytically active domain, was more highly conserved than the amino terminus.
      The 89% amino acid sequence similarity between the murine ras recision gene and
      human lysyl oxidase suggests that they are the same gene product. Therefore, in
      addition to cross linking of extracellular matrix proteins, lysyl oxidase may
      have a direct role in tumor suppression. Northern blot analysis of poly A+RNA
      from cultured skin fibroblasts revealed at least three-distinct transcripts,
      sized 4.8 kb, 3.8 kb and 2.0 kb. In addition, using a panel of human mouse cell
      hybrids, the lysyl oxidase gene was assigned to human chromosome 5.

PMID- 1357536
TI  - [Lymphoid germinative centers reservoir of HIV].

PMID- 1357537
TI  - Method of intraoperative monitoring of neuromuscular function and residual
      blockade in the recovery room.
AB  - We evaluated the method used intraoperatively to assess the degree of
      neuromuscular blockade prior to pharmacologic reversal to determine its role in
      preventing residual blockade in the postanesthesia care unit (PACU). We studied
      38 patients who received a nondepolarizing muscle relaxant during general
      anesthesia for carotid endarterectomy or thoracotomy. The anesthesiologist
      assessed the degree of neuromuscular blockade intraoperatively prior to
      pharmacologic reversal either by the standard method of visually counting the
      number of evoked thumb twitches elicited by supramaximal train-of-four
      stimulation of the ulnar nerve (i.e., thumb train-of-four count), or by an
      alternative method such as 1) visually counting the number of evoked orbicularis
      oculi muscle twitches elicited by supramaximal train-of-four stimulation of the
      facial nerve, or 2) observing the patient for clinical evidence of partial
      recovery (e.g., swallowing or attempts to breathe). Residual blockade in the PACU
      was defined as 1) a train-of-four ratio less than 0.70 (measured by a
      mechanomyograph), or 2) the inability of the patient to perform clinical tests of
      neuromuscular function (e.g., a sustained head lift for 5 seconds) and evidence
      of neuromuscular weakness that was resolved following administration of
      edrophonium. Five of the 22 patients (23%) in whom one of the alternative methods
      was used had residual blockade in the PACU; none of the 16 patients with a thumb
      train-of-four count of 3 or 4 before pharmacologic reversal of NMB had residual
      blockade in the PACU (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357538
TI  - 6th European Congress of Clinical Neurophysiology. Lisbon, Portugal, 19-22
      September 1992. Abstracts.

PMID- 1357539
TI  - Activation of the Rhizobium leguminosarum glnII gene by NtrC is dependent on
      upstream DNA sequences.
AB  - The cloning and sequence determination is reported of the DNA region of Rhizobium
      leguminosarum coding for glutamine synthetase II (GSII). An open reading frame
      (ORF) encoding 326 amino acids was defined as the glnII gene on the basis of its
      similarity to other glnII genes and the ability of a DNA fragment carrying this
      ORF to complement the glutamine auxotrophy of a Klebsiella pneumoniae glnA
      mutant. We find that the glnII gene in R. leguminosarum is transcribed as a
      monocistronic unit from a single promoter, which shows structural features
      characteristic of rpoN (ntrA)-dependent promoters. In K. pneumoniae, such
      promoters require the ntrC and rpoN (ntrA) gene products for transcription. The
      intracellular level of glnII mRNA changes when R. leguminosarum is grown on
      different nitrogen sources, as expected for regulation by the nitrogen regulatory
      system. Promoter deletion analysis has shown that an extensive upstream DNA
      sequence (316 bp) is essential for in vivo activation of the glnII promoter in
      different biovars of R. leguminosarum. This DNA region requires a wild-type ntrC
      gene for activity and includes two conserved putative NtrC-binding site
      sequences. The results conclusively show that transcription from the R.
      leguminosarum glnII promoter is fully dependent on positive control by NtrC
      protein and on an upstream activator sequence (UAS).

PMID- 1357540
TI  - Chromosomal localization of HTLV-1 viral integration sites using in situ
      hybridization: detection of a novel IL2R fragment.
AB  - The presence of human T-cell leukemia virus (HTLV-1) in patients with adult T
      cell leukemia (ATL) was investigated by Southern blotting and in situ
      hybridization. In all seven patients, HTLV-1 provirus was detected. A large and
      variable number of labeled restriction fragments were observed, indicating
      multiple integrations. Two of the patients analyzed by in situ hybridization had
      two, while the third patient had three, sites of viral integration on six
      different chromosomes, suggesting random integration. A single site of
      integration was shared by two patients, which was on chromosome 10 at bands p11-
      >p15. One of these sites was on an apparently normal chromosome 10 and the other
      was on a derivative chromosome 10,t(10;14)(p12;q32). The interleukin 2 receptor
      (IL2R) has previously been localized to this region (10p14-->p15). The alpha
      chain of the IL2R is continuously expressed on affected T-cells in this disease.
      Southern blotting with pIL2R showed the presence of a novel 3.5 kb fragment in
      five out of the seven patients. This novel fragment has not been previously
      reported. No direct correlation was found between the novel 3.5 kb fragment,
      present in patients both cytogenetically normal and abnormal, and viral
      integration in the 10p11-->p15 region in two patients. Therefore, it is suggested
      that the presence of the 3.5 kb fragment and the numerous chromosomal breaks
      associated with this disease may not be direct results of viral integration.

PMID- 1357541
TI  - Characterization of rat white fat cell alpha 1B-adrenoceptors.
AB  - In isolated rat white adipocytes, epinephrine (in the presence of 10 microM
      propranolol) increased the uptake of [32P]Pi into phosphatidylinositol in a dose
      dependent fashion. When the cells were pretreated with the irreversible
      antagonist chlorethylclonidine, this alpha 1-adrenergic effect was markedly
      diminished. The effect of epinephrine was dose-dependently antagonized by
      selective alpha 1-adrenergic antagonists, with the potency order prazosin greater
      than 5-methylurapidil greater than or equal to WB4101. Binding studies using
      crude membrane preparations were performed with the ligands [3H]bunazosin and
      125I-HEAT. Both ligands bound to membrane sites with high affinity (Kd values of
      0.75 +/- 0.20 nM for [3H]bunazosin and 125 +/- 20 pM for 125I-HEAT), in a rapid,
      reversible, and saturable (Bmax, 9-12 fmol/mg of protein) fashion, and with the
      expected pharmacological characteristics for alpha 1-adrenoceptors. Binding
      displacement studies with these ligands indicated a potency order of prazosin
      greater than 5-methylurapidil greater than or equal to WB4101. Northern blot
      analysis using receptor subtype-specific gene probes showed that adipocyte mRNA
      hybridized with the alpha 1B-adrenergic probe. All these data suggest that the
      alpha 1-adrenoceptors of rat white adipocytes belong to the alpha 1B subtype.

PMID- 1357542
TI  - Intrinsic activity determinations at the dopamine D2 guanine nucleotide-binding
      protein-coupled receptor: utilization of receptor state binding affinities.
AB  - Guanine nucleotide-binding protein-coupled receptors have been shown to exist in
      both a high affinity agonist (HiAg) and a low affinity agonist (LowAg) state. The
      formation of the HiAg state is promoted by agonists, and the formation of this
      state of the receptor appears to be a critical factor in the generation of the
      effector-activating complex G alpha.GTP.Mg2+ and in the production of a stimulus.
      The magnitude of the difference in the affinity a compound has for the HiAg
      versus the LowAg state of the receptor has been related to the intrinsic activity
      of the compound. In this paper the HiAg and LowAg affinities (Ki) of full and
      partial dopamine agonists of varying levels of intrinsic activity were determined
      using membranes from Chinese hamster ovary cells stably transfected with the D2i
      receptor. The HiAg state was defined using the recently described dopamine
      agonist ligand [3H]U-86170, and the LowAg state was defined using [3H] raclopride
      plus 600 microM GTP. The LowAg/HiAg ratios for apomorphine (43), HW-165 (12.5), (
      )-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(-)-3-PPP] (4.5), terguride (1.6),
      SDZ-208-911 (1.2), and SDZ-208-912 (0.3) were found to correlate well with their
      electrophysiologically derived intrinsic activities (r = 0.92). Using this
      relationship, the intrinsic activity for compounds such as (+)-3-PPP (112%),
      quinpirole (104%), U-68553B (102%), and U-86170 (95%) was predicted to be high
      (greater than 90%); (-)-apomorphine (73%) was of high/moderate intrinsic
      activity, HW-165 (52%), (+)-apomorphine (51%), and (-)-3-PPP (34%) were in the
      intermediate range, and terguride (16.5%), SDZ-208-911 (11.7%), and SDZ-208-912 (
      12%) were at the lower end of the intrinsic activity spectrum. The receptor state
      binding-determined intrinsic activity values for quinpirole (100%), U-86170F
      (94.8%), HW-165 (52.1%), (-)-3-PPP (34.3%), SDZ-208-911 (11.7%), and SDZ-208-912
      (-12%) were found to correlate well (r = 0.908) with their maximum response
      (intrinsic activity), as determined using ATP-mediated increases in arachidonic
      acid release from CHO-D2i cells. In addition, the maximal effect of several of
      these compounds on rat striatal homovanillic acid (HVA) levels was determined.
      The drug-induced changes in tissue HVA levels were found to be consistent with
      the affinity-derived intrinsic activities of the drugs.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1357544
TI  - Effect of chronic estradiol treatment on brain dopamine receptor reappearance
      after irreversible blockade: an autoradiographic study.
AB  - Quantitative autoradiography was used to investigate dopamine receptor
      repopulation kinetics after irreversible dopamine receptor inactivation with N
      ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The striatum and substantia
      nigra of two groups of ovariectomized female rats were compared. One group of
      rats was pretreated with estradiol (10 micrograms, twice daily, for 2 weeks), and
      another group received the vehicle. Striatal D1 dopamine receptors had larger
      degradation and production rate constants, compared with D2 receptors. The D2
      receptor degradation rate constant increased rostro-caudally in the striatum of
      vehicle-treated rats, whereas this was not observed for estradiol-treated
      animals. A trend similar to that for D2 receptors was observed for the D1
      receptor degradation rate constant in the striatum of vehicle-treated rats,
      whereas in estradiol-treated animals this constant decreased rostro-caudally. In
      the anterior and the middle parts of the striatum D2 receptor recovery parameters
      were not affected by chronic estradiol treatment, but in the posterior part
      estradiol-treated rats had lower receptor degradation and production rate
      constants. In the anterior part of the striatum, chronic estradiol treatment did
      not affect the recovery parameters of D1 receptors, whereas lowered receptor
      degradation and production rate constants were observed in the middle and
      posterior parts. D1 receptor recovery parameters in the substantia nigra were not
      affected by chronic estradiol treatment. After EEDQ administration to vehicle
      treated rats, striatal dopamine levels decreased gradually, to reach a minimum 4
      days later, and returned to control values after 7 days. In estradiol-treated
      rats, however, dopamine levels increased 2 days after EEDQ. Levels of the
      dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid increased
      in the striatum after EEDQ administration in vehicle-treated rats. Even greater
      increases that lasted longer were observed in estradiol-treated rats after EEDQ.
      Striatal levels of serotonin and its metabolite 5-hydroxyindoleacetic acid were
      not significantly affected by EEDQ or estradiol administration. In summary,
      estradiol decreased striatal D1 and D2 receptor degradation rate constants, with
      the greatest effect being observed in the caudal part of the striatum. EEDQ
      dopamine receptor inactivation also revealed an increase of dopamine and its
      metabolites in the striatum after estradiol treatment.

PMID- 1357543
TI  - Different calcium-mobilizing receptors share the same guanine nucleotide-binding
      protein pool in hepatocytes.
AB  - High affinity binding of epinephrine to the alpha 1-adrenoceptor reflects the
      association of the ligand-receptor complex with a guanine nucleotide-binding
      protein (G protein) and thereby allows the receptor-G protein interaction to be
      assessed by radioligand binding methods. We have used [3H]prazosin/epinephrine
      competition binding to rat liver plasma membranes to examine the effects of other
      Ca(2+)-mobilizing hormones on the interaction between the alpha 1-adrenoceptor
      and its G protein. The aim of our experiments was to test whether the different
      Ca(2+)-mobilizing receptors in liver share the same limited pool of G proteins.
      [Arg8] Vasopressin (AVP) caused a concentration-dependent (EC50 = 0.49 +/- 0.03
      nM) inhibition of the extent to which epinephrine formed a high affinity complex
      with the alpha 1-adrenoceptor; antagonist binding was unaffected by AVP. The
      effect of AVP was competitively antagonized (Kd = 0.27 +/- 0.10 nM) by a
      selective peptide antagonist of the V1 vasopressin receptor. We conclude that, in
      rat hepatocytes, alpha 1-adrenoceptors and V1 vasopressin receptors converge to
      interact with the same pool of G proteins.

PMID- 1357545
TI  - [Multiple resistance of eukaryotic cells caused by P-glycoprotein].
AB  - Recent data concerning cloning and sequencing of mdr genes involved in multiple
      drug resistance in higher eukaryotes are reviewed. Structures of ABC-superfamily
      members, including the mdr products as well as mechanisms of their
      superproduction at various levels are considered. The possible role of MDR
      transporter in normal tissues and various approaches to overcoming the MDR
      phenotype are discussed. Non-P-glycoprotein mechanisms of drug resistance capable
      to modify MDR phenotype and applications of mdr in biotechnology are provided.

PMID- 1357547
TI  - Identification of a cis-regulatory element mediating somatostatin inhibition of
      epidermal growth factor-stimulated gastrin gene transcription.
AB  - Antral gastrin secretion and gene expression is inhibited by the paracrine
      release of somatostatin from antral D cells. Transforming growth factor-alpha and
      epidermal growth factor (EGF) stimulate gastrin reporter gene constructs when
      transfected into pituitary GH4 cells. Somatostatin inhibits EGF stimulation of
      gastrin gene expression, which is in part mediated at the level of
      transcriptional regulation as somatostatin inhibits EGF stimulation of gastrin
      reporter gene constructs. Somatostatin inhibition was abolished by pertussis
      toxin, indicating somatostatin inhibits transcription through the inhibitory G
      protein Gi. Somatostatin inhibition was unaffected by vanadate and okadaic acid,
      implying this inhibitory pathway is mediated neither through phosphotyrosine
      phosphatases nor serine/threonine phosphatases, respectively. Gastrin reporter
      genes containing 82 base pairs of the 5'-flanking DNA were sufficient to confer
      both EGF responsiveness and inhibition by somatostatin in GH4 cells. However,
      transcription of a gastrin reporter gene construct containing only the EGF
      response element (GGGGCGGGGTGGGGGG), located at -68 to -53, was stimulated by EGF
      but was not inhibited by somatostatin. Thus, somatostatin inhibits EGF-stimulated
      gastrin gene transcription by a mechanism other than by interfering with cell
      signals elicited by the EGF receptor. Since the 82 GASCAT is inhibited by
      somatostatin, this result also implies that sequences adjacent to the EGF
      response element contain a cis-regulatory element mediating transcriptional
      inhibition by somatostatin. This cis-element was located using gastrin reporter
      genes comprising sequential segments of the human gastrin promoter sequence from
      the transcriptional start site to -82 in the 5'-flanking DNA. Gastrin
      oligonucleotide constructs lacking the D oligonucleotide (gatcCATATGGCAGGGTA),
      located at -82 to -69 in the 5'-flanking DNA, were not inhibited by somatostatin,
      indicating that a somatostatin inhibitory cis-element is located between -82 and 
      69 in the 5'-flanking DNA of the human gastrin promoter.

PMID- 1357548
TI  - Analysis of HIV-1 expression in vivo with in situ hybridization and the
      polymerase chain reaction.
AB  - The objective of the present study was to compare the data of in situ
      hybridization (ISH), RNA polymerase chain reaction (PCR/RNA) and p24 core antigen
      (p24 Ag) enzyme immunoassay (EIA) for the detection of HIV-1 expression in
      peripheral blood mononuclear cells (PBMCs) and in plasma of infected patients at
      various CDC stages. PBMCs of 24 patients mostly of CDC stage II were obtained
      from heparinized blood samples, cytocentrifuged and hybridized with a (35S)
      labelled single-stranded RNA probe specific for gag-pol of LAVBru HIV-1 allowing
      the detection of genomic and/or messenger RNA. The corresponding plasma samples
      were used for the determination of p24 Ag by EIA and detection of HIV-1 genomic
      RNA by RT-PCR using specific primers in the LTR, gag and env regions. Whereas p24
      was detected in only six out of 24 patients, both ISH and PCR/RNA enabled the
      detection of viral RNAs in more than 60% of the patients; cumulation of positive
      results of ISH and RT-PCR showed that 100% of patients at stage IV and 83% of
      patients at stages II/III have molecular signs of HIV expression therefore
      indicating that transcription of the provirus is a highly frequent event, even in
      the early stages of the disease, and, pleading for undertaking a very early
      antiviral chemotherapy.

PMID- 1357546
TI  - Interactions between double-stranded RNA regulators and the protein kinase DAI.
AB  - The interferon-induced protein kinase DAI, the double-stranded RNA (dsRNA)
      activated inhibitor of translation, plays a key role in regulating protein
      synthesis in higher cells. Once activated, in a process that involves
      autophosphorylation, it phosphorylates the initiation factor eIF-2, leading to
      inhibition of polypeptide chain initiation. The activity of DAI is controlled by
      RNA regulators, including dsRNA activators and highly structured single-stranded
      RNAs which block activation by dsRNA. To elucidate the mechanism of activation,
      we studied the interaction of DAI with RNA duplexes of discrete sizes. Molecules
      shorter than 30 bp fail to bind stably and do not activate the enzyme, but at
      high concentrations they prevent activation by long dsRNA. Molecules longer than
      30 bp bind and activate the enzyme, with an efficiency that increases with
      increasing chain length, reaching a maximum at about 85 bp. These dsRNAs fail to
      activate at high concentrations and also prevent activation by long dsRNA.
      Analysis of complexes between dsRNA and DAI suggests that at maximal packing the
      enzyme interacts with as little as a single helical turn of dsRNA (11 bp) but
      under conditions that allow activation the binding site protects about 80 bp of
      duplex. When the RNA-binding site is fully occupied with an RNA activator, the
      complex appears to undergo a conformational change.

PMID- 1357549
TI  - A PCR-based assay for the wild-type dystrophin gene transferred into the mdx
      mouse.
AB  - Myoblast transfer has emerged as a promising treatment for inherited myopathies
      such as Duchenne muscular dystrophy (DMD). Further development of the technique's
      therapeutic potential requires an experimental system in which issues of graft
      rejection can be clearly discriminated from those related to myoblast biology.
      Here we report the development and initial application of a quantitative assay
      for myogenic cells bearing a wild-type dystrophin gene following transfer into
      the mdx mouse. The technique relies upon the ability of a mutagenizing polymerase
      chain reaction (PCR) primer to create a new restriction site in the amplification
      production of the wild-type, but not the mdx dystrophin gene. The ratio of host
      to donor cells can be determined from muscle biopsies as small as 1 mg,
      regardless of donor H-2 background. This simple technique should allow a number
      of basic questions related to myoblast and direct gene transfer to be addressed
      using the mdx mouse model.

PMID- 1357550
TI  - Long-term effects of a long-acting beta 2-adrenoceptor agonist, salmeterol, on
      airway hyperresponsiveness in patients with mild asthma.
AB  - BACKGROUND: Asthma is characterized by hyperresponsiveness of the airways to
      bronchoconstrictive stimuli. Long-acting beta 2-adrenoceptor agonists have been
      introduced as a new therapeutic approach, but there is growing concern about
      whether control of asthma may deteriorate with the regular use of these agents.
      We investigated the long-term effects of the beta 2 agonist salmeterol on
      bronchodilation and on airway hyperresponsiveness to the bronchoconstrictive
      agent methacholine in mild asthma. METHODS: In a parallel, double-blind study, 24
      patients with mild asthma were randomly assigned to treatment with either inhaled
      salmeterol (50 micrograms, twice daily) (n = 12) or placebo (n = 12) during an
      eight-week trial. Methacholine challenge was performed before, during, and after
      the treatment period. Methacholine responsiveness was measured as the provocative
      concentration (PC20) that caused a 20 percent decrease in the forced expiratory
      volume in one second (FEV1). RESULTS: There was a significant increase in FEV1
      one hour after the inhalation of salmeterol (P = 0.006), which did not differ
      significantly on days 0, 28, and 56 of the treatment period (increase, 9.8, 9.4,
      and 8.8 percent of predicted FEV1, respectively; P = 0.91). On the first
      treatment day, salmeterol afforded significant protection against methacholine
      induced bronchoconstriction, as shown by a 10-fold increase in the PC20 as
      compared with the value at entry (P less than 0.001). After four and eight weeks
      of treatment, however, the salmeterol-induced change in the PC20 was
      significantly attenuated (P less than 0.001) to only a twofold increase. Two and
      four days after treatment ended, the PC20 was not significantly different from
      the value before treatment (P = 0.15). CONCLUSIONS: Regular treatment of patients
      with mild asthma with salmeterol leads to tolerance to its protective effects
      against a bronchoconstrictor stimulus, in this case inhaled methacholine, despite
      well-maintained bronchodilation. This finding raises concern about the
      effectiveness of prolonged therapy with long-acting beta 2-adrenoceptor agonists
      in asthma.

PMID- 1357551
TI  - Tolerance to the nonbronchodilator effects of inhaled beta 2-agonists in asthma.
AB  - BACKGROUND: Tolerance to the direct bronchodilator effects of beta 2-agonists
      does not appear to occur in asthma. However, it is not known whether this is true
      for the nonbronchodilator effects of these agents, which protect the airways
      against bronchoconstrictive stimuli. METHODS: We investigated whether tolerance
      develops to the protective effect of inhaled terbutaline on airway responsiveness
      to the bronchoconstrictors methacholine (which acts directly on airway smooth
      muscle) and AMP (which acts indirectly by stimulating the release of mediators
      from mast cells) during sustained treatment with terbutaline. In a randomized,
      double-blind, crossover study, 12 patients with mild asthma each inhaled a single
      dose of terbutaline (500 micrograms) or placebo before a challenge with a series
      of doubling doses of inhaled methacholine or AMP, before and after treatment for
      seven days with 500 micrograms of terbutaline four times daily or placebo.
      RESULTS: Before the seven days of treatment with terbutaline, a single dose of
      terbutaline reduced airway responsiveness to methacholine by 2.7 doubling doses
      (95 percent confidence interval, 1.9 to 3.5), but it had an even greater
      protective effect against AMP, reducing airway responsiveness by 3.8 doubling
      doses (95 percent confidence interval, 2.7 to 4.9; P less than 0.001). After
      seven days of treatment with terbutaline, the protective effect of terbutaline
      against methacholine decreased to 2.2 doubling doses (95 percent confidence
      interval, 1.3 to 3.0; P = 0.04), and that against AMP decreased even more, to 1.7
      doubling doses (95 percent confidence interval, 1.1 to 2.4; P less than 0.001).
      By contrast, the bronchodilator response to terbutaline was unchanged during
      seven days of treatment with this agent. CONCLUSIONS: We observed tolerance to
      the nonbronchodilator actions of the inhaled beta 2-agonist terbutaline in
      patients with mild asthma, an effect that may be more pronounced in mast cells
      than in bronchial smooth muscle. This property of beta-agonists may constitute a
      drawback to their regular use in patients with asthma.

PMID- 1357552
TI  - Treatment for Alzheimer's disease?

PMID- 1357553
TI  - A comparison of bronchodilator therapy with or without inhaled corticosteroid
      therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease
      Study Group.
AB  - BACKGROUND: The morbidity from obstructive airways disease (asthma and chronic
      obstructive pulmonary disease) is considerable, and the mortality rate is rising
      in several countries. It has been hypothesized that long-term improvement in
      prognosis might result from vigorous bronchodilator or antiinflammatory therapy.
      METHODS: In a multicenter trial we compared three inhalation regimens in which a
      beta 2-agonist (terbutaline, 2000 micrograms daily) was combined with a
      corticosteroid (beclomethasone, 800 micrograms daily), an anticholinergic
      bronchodilator (ipratropium bromide, 160 micrograms daily), or placebo. Patients
      with airways hyperresponsiveness and obstruction who were 18 to 60 years old were
      followed for 2 1/2 years. RESULTS: Of the 274 patients enrolled, 56 percent had
      allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent
      of the predicted value. The mean PC20 (the concentration of inhaled histamine
      causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26
      mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms,
      was less frequent in the corticosteroid group (12 of 91 patients) than in the
      anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91
      patients; P < 0.001). The mean FEV1 (+/- SE) increased by 10.3 +/- 1.3 percent of
      the predicted value in the corticosteroid group within three months and remained
      stable thereafter, whereas it did not change in the other two groups (P < 0.001).
      The PC20 increased by 2.0 doubling concentrations in the corticosteroid group but
      did not change in the other groups (P < 0.001). In the corticosteroid group,
      patients who did not smoke, who had allergies, or who were less than 40 years old
      benefited more from their treatment than did those who smoked, did not have
      allergies, or were over 40, but all subgroups of the corticosteroid group had
      improvement as compared with the anticholinergic-drug or placebo group.
      CONCLUSIONS: The addition of an inhaled corticosteroid--but not an inhaled
      anticholinergic agent--to maintenance treatment with a beta 2-agonist
      (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways
      obstruction in patients with a spectrum of obstructive airways disease.

PMID- 1357554
TI  - A comparison of salmeterol with albuterol in the treatment of mild-to-moderate
      asthma.
AB  - BACKGROUND: An effective, long-acting bronchodilator could benefit patients with
      asthma who have symptoms not controlled by antiinflammatory drugs. We compared a
      new long-acting, inhaled beta 2-adrenoceptor agonist, salmeterol, with a short
      acting beta 2-agonist, albuterol, in the treatment of mild-to-moderate asthma.
      METHODS: We randomly assigned 234 patients (150 male and 84 female patients 12 to
      73 years old) to one of three treatment groups: one group received 42 micrograms
      of salmeterol twice daily, one received 180 micrograms of albuterol four times
      daily, and one received placebo. Treatment was assigned in a double-blind
      fashion, and all patients could use supplemental inhaled albuterol as needed
      during the 12-week treatment period. RESULTS: Measurements of the forced
      expiratory volume in one second, performed hourly for 12 consecutive hours,
      showed that a single dose of salmeterol produced a greater mean area under the
      curve than two doses of albuterol taken 6 hours apart (6.3 vs. 4.9 liter.hr, P <
      0.05). The difference was significant on day 1 and at week 4 of the study, but
      not at week 8 or 12. Salmeterol was also more effective than albuterol or placebo
      (with albuterol taken as needed) in increasing the morning peak expiratory flow
      rate: salmeterol induced a mean increase of 24 liters per minute over the
      pretreatment values, as compared with a decrease of 6 liters per minute with
      albuterol (P < 0.001) and an increase of 1 liter per minute with placebo (P =
      0.002). The mean overall symptom score was improved most by salmeterol treatment
      (P < 0.05), with the number of days with symptoms and of nights with awakenings
      decreasing by 22 percent and 52 percent, respectively; there were no differences
      in results between albuterol treatment and placebo administration. We found no
      evidence of tolerance to the bronchodilating effects of salmeterol, and adverse
      reactions to all the treatments were infrequent and mild. CONCLUSIONS: For the
      management of mild-to-moderate asthma, salmeterol given twice daily is superior
      to albuterol given either four times daily or as needed.

PMID- 1357555
TI  - Direct evidence for extensive paternal mitochondrial DNA inheritance in the
      marine mussel Mytilus.
AB  - Inheritance of mitochondrial DNA in animals was thought to be strictly maternal.
      Recently, evidence for incidental paternal mtDNA leakage was obtained in hybrid
      crosses of Drosophila and mice. In mice, the frequency of paternal mtDNA
      contributions was estimated at 10(-4), compared with maternal contributions. The
      common occurrence in the marine mussel Mytilus of heteroplasmic individuals with
      two or more types of highly diverged mtDNA molecules was interpreted as strong
      evidence for biparental mtDNA inheritance by some, but not by others. We report
      here results from pair-matings involving two species of mussels, Mytilus edulis
      and Mytilus trossulus. Extensive contribution of paternal mtDNA, amounting to
      several orders of magnitude higher than that inferred for Drosophila or mice, was
      observed in both intra- and interspecific crosses.

PMID- 1357556
TI  - Chaperones classified.

PMID- 1357557
TI  - Celiprolol exerts microvascular dilatation by activation of beta 2-adrenoceptors.
AB  - In order to clarify the question whether the beta 1-selective adrenoceptor
      antagonist celiprolol possesses vasodilating properties, isolated vascular
      networks were perfused with increasing concentrations of celiprolol (in a
      cumulative manner) ranging from 10(-8) to 10(-4) mol/l. The study was carried out
      using the isolated mesenteric vascular bed of the guinea pig mesenterium coli.
      Vascular diameters of four different vascular regions [vessels classified as G1
      (585 +/- 30 microns), G2 (403 +/- 25 microns), G3 (282 +/- 27 microns) and G4
      (197 +/- 13 microns)] were assessed by means of microscopic videoangiometry.
      Perfusion with celiprolol resulted in concentration dependent vasodilation which
      was more pronounced in G3 and G4 vessels. In addition, cumulative concentration
      response curves were determined from responses obtained in the presence of 10(
      8), 10(-7), 10(-6) and 10(-4) mol/l ICI 118,551 (a highly selective adrenoceptor
      antagonist). In the presence of ICI 118,551 at concentrations greater than or
      equal to 10(-6) mol/l, no celiprolol response could be observed. Lower
      concentrations of ICI 118,551 shifted the celiprolol concentration-response curve
      to the right in a concentration-dependent manner. Therefore, it is concluded (a)
      that celiprolol has a vasodilating effect, (b) that this vasodilation is produced
      by stimulation of beta 2-adrenoceptors and (c) that the vasodilating effect is
      more pronounced in smaller than in larger vessels (G3, G4 vs G1, G2).

PMID- 1357558
TI  - Modulation of cytosolic free calcium concentration by alpha 1-adrenoceptors in
      rat atrial cells.
AB  - The effects of alpha 1-adrenoceptor stimulation by phenylephrine (PE) and beta
      adrenoceptor stimulation by isoprenaline (ISO) on Ca2+ current (ICa) and free
      intracellular Ca2+ concentration ([Ca2+]i) were studied in isolated atrial
      myocytes from rat hearts. PE did not significantly affect the magnitude of ICa,
      whereas large increases of peak ICa were observed in response to ISO. In
      electrically driven cells, PE evoked a concentration-dependent, gradual increase
      in diastolic [Ca2+]i and, initially, an increase in the height of peak [Ca2+]i
      transients. When the diastolic [Ca2+]i was increased to a greater extent, the
      amplitude of [Ca2+]i transients was decreased. Simultaneous measurements of
      [Ca2+]i and membrane potential showed that the increase in diastolic [Ca2+]i was
      associated with a depolarization of the membrane, and the greater amplitude of
      [Ca2+]i transients with a prolongation of the action potential (AP). The PE
      induced increase in diastolic [Ca2+]i was eliminated when the cells were voltage
      clamped at the original resting membrane potential (RP); under these conditions,
      an increase in [Ca2+]i transients was observed in response to PE. ISO usually
      caused larger increases in the amplitude of [Ca2+]i transients with only minor
      changes in diastolic [Ca2+]i. These results suggest that PE and ISO increase the
      amplitude of [Ca2+]i transients in rat atrium in different ways. The increase in
      [Ca2+]i transients in response to beta-adrenoceptor stimulation is commonly
      thought to be mediated by a greater conductance of voltage-dependent Ca2+
      channels causing a greater Ca2+ influx and a release of more Ca2+ from the
      sarcoplasmic reticulum during the AP. The increase in diastolic [Ca2+]i in
      response to PE is probably a consequence of the depolarization of the membrane,
      possibly involving the voltage-dependent Na(+)-Ca2+ exchange mechanism.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1357559
TI  - Vasodilating properties of KRN2391: structural basis of a new pyridine-type
      potassium channel opener with a nitrate moiety.
AB  - The vasodilating mechanism of a new compound, cyanoimino-3
      pyridylmethylaminoethyl nitrate methanesulfonate (KRN2391), a derivative of
      nicorandil, was examined in the isolated rabbit aorta. To elucidate the structure
      activity relationship, a comparison was made with the two denitrated derivatives:
      cyanoimino-3-pyridylmethylaminoethyl acetate methanesulfonate (Ki4032) and
      cyanoimino-3-pyridylmethylaminoethyl alcohol (Ki3315). In preparations
      precontracted with phenylephrine (10(-7) mol/l), KRN2391, Ki4032 and Ki3315
      caused concentration-dependent relaxation. pD2 values (-log [EC50]) were 6.74 +/-
      0.03, 5.67 +/- 0.05 and 3.63 +/- 0.03, respectively. Both methylene blue and
      glibenclamide produced a shift to the right of the concentration-response curves
      for KRN2391. The shift by glibenclamide became greater in the presence of
      methylene blue. An elevation of the cGMP content was not detected until the
      concentration of KRN2391 was increased to a level enough to produce a full
      relaxation (3 x 10(-6) mol/l). In contrast, in the case of Ki3315 a parallel
      shift to the right of the concentration-response curve was observed after
      glibenclamide (10(-5) mol/l). Methylene blue (10(-5) mol/l) had no effect on the
      concentration-response curve, and there was no increase in cyclic GMP (cGMP) with
      10(-3) mol/l of the compound. The concentration-response curve of Ki4032 was also
      attenuated by glibenclamide. Though this compound lacks the nitrate moiety, it
      (10(-4) mol/l) showed a slight tendency to increase the cGMP content, and
      methylene blue slightly but significantly modified the concentration-response
      curve of this compound. However, the co-administration of glibenclamide and
      methylene blue resulted in no further modification of the concentration
      relaxation curve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357560
TI  - RPA, NIDDK break new ground in combining clinical, legislative agendas.

PMID- 1357561
TI  - [Secondary prevention of ischemic heart disease: a campaign on 2 fronts].

PMID- 1357562
TI  - Porphyria cutanea tarda in a patient with AIDS.
AB  - A 53-yr-old man, known to have had AIDS for 6 months, developed the clinical
      signs and symptoms of porphyria cutanea tarda (PCT) preceding deterioration of
      his illness. Urinary porphyrin analysis confirmed the diagnosis of PCT. At the
      time the cutaneous blistering and scars developed, he was taking zidovudine and
      fluconazole. Reviewing the literature suggested that association of the two
      disorders is not purely coincidental. Anaemia, due to chronic immune activation
      and therapeutic options in the light of AIDS, could play an important role in the
      development of PCT. We recommend analysing the urine for porphyrins in HIV
      positive patients who have chronic photosensitivity of the skin.

PMID- 1357563
TI  - Activation of striatal tyrosine hydroxylase by neurocatin, a neuroregulator from
      mammalian brain.
AB  - Neurocatin, a neuroregulatory factor isolated from mammalian brain, is a powerful
      affector of dopamine synthesis in striatal rat synaptosomes. Incubation of intact
      synaptosomes with neurocatin caused an increase in the rate of dopamine synthesis
      measured by accumulation of DOPA. The increase is rapid (within two minutes) and
      dependent on the concentration of added neurocatin. The stimulatory effect of
      neurocatin on dopamine synthesis occurred only in intact synaptosomes and was
      almost completely abolished by lysis of the synaptosomes with Triton X-100 or
      sonification prior to neurocatin addition. The kinetic parameters of tyrosine
      hydroxylase were measured in lysates prepared from synaptosomes preincubated with
      neurocatin. These showed that with increasing neurocatin concentration there was
      an increase in Vmax with no significant change in KM for the pteridine cofactor,
      compared to control. Activation of tyrosine hydroxylase by neurocatin is at least
      partially caused by a receptor mediated increase in phosphorylation of the
      enzyme. Protein kinase C and protein kinase II may be involved in this process.

PMID- 1357564
TI  - Serotonergic pathology is not widespread in Alzheimer patients without prominent
      aggressive symptoms.
AB  - Behavioural symptoms of Alzheimer's disease, such as aggression, may determine
      the care patients required. Most postmortem neurochemical studies have been of
      institutionalized patients and conclusions drawn from these may not be valid for
      all patients. We have shown that serotonin 2 receptors are not lost from 12 of
      the 13 areas of cerebral cortex examined in the patients assessed to be free of
      aggressive symptoms. This has been interpreted as representing the relative
      preservation of cortical interneurones. In contrast choline acetyltransferase
      activity was reduced in all areas whereas serotonin content was reduced in only 2
      of the 4 areas examined.

PMID- 1357566
TI  - Involvement of synaptosomal neurotransmitter amino acids in audiogenic seizure
      susceptibility and -severity of Rb mice.
AB  - The involvement of synaptosomal neurotransmitter amino-acids in seizure
      susceptibility and seizure severity was explored. The amino-acid contents of
      brain synaptosomes were determined in three sublines of Rb mice differing in
      their response to an acoustic stimulus: Rb1, clonic-tonic seizure-prone, Rb2,
      clonic seizure-prone, and Rb3, seizure-resistant. Synaptosomes were prepared from
      6 brain areas considered to be involved in seizure activity: olfactory bulbs,
      amygdala, inferior colliculus, hippocampus, cerebellum, pons-medulla. The steady
      state levels of GABA and glycine (Gly), inhibitory amino-acids, of taurine (Tau),
      an inhibitory neurotransmitter of neuromodulator, of aspartate (Asp) and
      glutamate (Glu), excitatory amino-acids, as well as of serine (Ser) and glutamine
      (Gln), two precursors of neurotransmitter amino-acids, were determined by HPLC.
      Low levels of Tau, GABA, and Ser in hippocampus, Gly in amygdala, Glu in
      hippocampus, inferior colliculus and pons, Gln and Asp in inferior colliculus
      appeared to correlate with seizure-susceptibility. GABA and Asp in olfactory
      bulb, Gln in amygdala, hippocampus and pons, ser in olfactory bulb and pons,
      appeared to be associated either with seizure-severity or -diversity. A strong
      involvement of hippocampus (Tau, GABA, Ser, Glu, and Gln) and inferior colliculus
      (Asp, Glu, Gln) in audiogenic seizure-susceptibility, and of olfactory bulb
      (GABA, Asp) in seizure-severity and/or -diversity is suggested.

PMID- 1357567
TI  - [Effect of metabolic stress on the release of glutamic acid and GABA in the brain
      tissue of Mongolian hamsters].
AB  - The concentrations of glutamic acid and GABA were determined in the brain tissue
      in gerbils under conditions simulating "metabolic stress", that is ischaemia,
      aglycaemia and anoxia. The material for the determinations was taken from
      fragments of the hippocampus incubated under these conditions in artificial
      cerebrospinal fluid, and the concentrations of these neurotransmitters were
      determined by histochemical methods in vitro. The release of glutamic acid and
      GABA into the extracellular space increased with longer duration of the
      incubation in a linear fashion in all experimental groups and was most pronounced
      in ischaemia. In case of calcium absence in the extracellular space inhibition
      was observed of the release of these neurotransmitters which suggested an
      important role of bivalent cations in the regulation of the studied process,
      especially under control conditions. During anoxia and ischaemia a considerable
      part of the release of glutamic acid and GABA seems to be calcium-independent
      which may suggest presence of additional sources of release of the amino acid
      neurotransmitters, apart from their release from the direct pool. It is possible
      that these sources are activated during metabolic stress involving nerve cells.

PMID- 1357568
TI  - [Clinical course and the results of the treatment of unilateral chronic subdural
      hematoma].
AB  - The authors analysed the clinical and surgical results in 131 patients treated
      for unilateral chronic subdural haematoma. 71% of patients had a history of head
      trauma, 34% were addicted to alcohol. In 18% of cases the clinical course
      mimicked cerebral stroke. All patients were treated by burr holes and closed
      system drainage lasting for 24-48 hours. There were 4 deaths, 3 from ischaemic
      stroke, and 1 from subdural empyema. 19 patients revealed postoperative
      complications--intracranial hypotension, cerebral oedema, and haematoma
      recurrence being the commonest. Follow-up revealed that 83% of patients were
      healthy, 10% had stable neurological deficit, and 7% presented epileptic fits.

PMID- 1357569
TI  - Amino acid neurotransmitter release in the preoptic area of rats during the
      positive feedback actions of estradiol on LH release.
AB  - To investigate the role of amino acid neurotransmitters in the regulation of LH
      secretion in ovariectomized (ovx) rats with or without estrogen substitution, we
      measured the release rates of gamma-aminobutyric acid (GABA), taurine, glycine,
      aspartate, glutamate, homocysteic acid, and also of the neurally inactive amino
      acids serine and glutamine in push-pull perfusate samples of the
      preoptic/anterior hypothalamic area (PO/AH) collected at 30-min intervals. To
      achieve this we had to develop a highly sensitive assay utilizing
      phenylisothiocyanate prederivatization which was followed by HPLC chromatography.
      In confirmation of our earlier results we observed again a conspicuous drop of
      preoptic GABA release prior to and during the time of estrogen-induced LH surge.
      In addition, the release rates of the excitatory amino acid neurotransmitters
      aspartate and glutamate in the PO/AH increased during this time. Interestingly,
      also secretion of taurine and glycine was increased during the LH surge, whereas
      preoptic release rates of serine and glutamine and of homocysteic acid, the
      putative endogenous ligand of the so-called N-methyl-D-aspartate receptor,
      remained unchanged. No such changes of amino acid neurotransmitters release rates
      were observed in ovx rats. This finding underlines that the changes of amino acid
      secretion in ovx estrogen-primed rats are likely due to the influence of the
      steroid rather than due to a diurnal rhythm. We conclude that GnRH neurons are
      under a tonic inhibitory tone exerted by GABA which is relieved during the time
      of the estrogen-induced LH surge. During this time, aspartate and glutamate may
      have additional stimulatory effects on GnRH neurons.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1357570
TI  - Estradiol regulation of somatostatin receptors in the arcuate nucleus of the
      female rat.
AB  - Somatostatin receptors on lactotroph cells of the anterior pituitary are
      positively regulated by estradiol. In the present work, we investigated whether
      estradiol regulation of somatostatin receptors also occurred in the female rat
      brain. 125I-Tyr0-DTrp8-somatostatin (125I-SRIF: 780 Ci/mM) was used as a ligand.
      Female adult rats were ovariectomized and treated or not with estradiol benzoate
      (20 micrograms/day for 1 or 8 days). In female brains, 125I-SRIF binding, as
      assessed by film radioautography, was high in the basolateral amygdala, CA1 field
      and dentate gyrus of the hippocampus and locus coeruleus, moderate in the median
      habenula and deep layers all through the cortex. Castration or estradiol
      treatment did not modify 125I-SRIF binding in these regions. By light-microscopic
      radioautography, a subpopulation of 125I-SRIF-labeled cells was localized in the
      ventrolateral portion of the arcuate nucleus. Ovariectomy alone did not
      significantly affect the number and binding density of 125I-SRIF-labeled cells in
      the arcuate nucleus. However, estradiol treatment in ovariectomized animals
      significantly increased both parameters. Along the estrus cycle, the number of
      125I-SRIF-labeled cells was not significantly modified but 125I-SRIF binding
      density was significantly higher in proestrus as compared to diestrus I, diestrus
      II and estrus. These results demonstrate that brain 125I-SRIF binding sites are
      positively regulated by estradiol only in the arcuate nucleus of the
      hypothalamus.

PMID- 1357565
TI  - Interactions of mast cells with the nervous system--recent advances.
AB  - This article reviews recent advances in the understanding of mast cell-nervous
      system interactions. It is drawn largely from work published within the last ten
      years, and discusses the anatomical and biochemical evidence of a functional
      connection between mast cells and the nervous system, and the implications that
      such a relationship may have for normal and abnormal physiological functioning.
      Mast cells are found at varying levels of association with the nervous system; in
      CNS parenchyma (mainly thalamus), in connective tissue coverings (e.g. meninges,
      endoneurium), and in close apposition to peripheral nerve endings in a variety of
      tissues. There is, as yet, no clearly defined role for mast cells in nervous
      system function, or vice-versa, and it seems most likely that their interactions
      fulfil mutually modulatory roles. By extension, pathological situations where one
      of the partners in this relationship is overly stimulated may lead to a
      dysregulation of the other, and contribute to disease symptomatology.

PMID- 1357571
TI  - Somatostatin and prosomatostatin immunoreactive nerve fibers in the bovine pineal
      gland.
AB  - An immunohistochemical study of the bovine pineal gland was performed by using
      polyclonal rabbit antisera raised against synthetic peptide fragments
      corresponding to the amino acid sequences of somatostatin-14, somatostatin-28,
      somatostatin-28 (1-12), and prosomatostatin (20-36). Immunoreactive nerve fibers
      were demonstrated in the pineal gland with all four antisera. The nerve fibers
      were located throughout the gland, both perivascularly and intraparenchymally,
      with the highest density of fibers in the proximal part, close to the pineal
      stalk. A number of immunoreactive nerve fibers were also found in the habenular
      area and stria medullaris projections. Some of the fibers in the stria medullaris
      projections could be followed into the pineal gland via the rostral part of the
      pineal stalk. A few immunoreactive nerve fibers were present in posterior
      commissure, in the subcommissural organ and pretectal area. Thus, the present
      study shows that the bovine pineal gland is innervated by nerve fibers containing
      all four sequences of prosomatostatin. The anatomical location of the
      somatostatin-immunoreactive nerve fibers in the bovine pineal gland indicates
      that the perikarya of some of these nerve fibers are located in the brain.

PMID- 1357572
TI  - Elevated CSF glutamate in Rett syndrome.
AB  - The concentration of free amino acids was measured in the cerebrospinal fluid of
      four patients with Rett syndrome. The reference material were patients with
      autistic disorder who had CSF aminoacid levels similar to those reported for
      healthy children. The concentration of glutamate-but of no other amino acid-was
      markedly elevated in the CSF of the RS patients. The results are discussed in the
      context of excitotoxicity in neurodegenerative disease.

PMID- 1357573
TI  - Ayurvedic (science of life) agents induce differentiation in murine neuroblastoma
      cells in culture.
AB  - Many Indian Ayurvedic (science of life) agents have been introduced into the
      U.S.A. as food supplements. Two of them, Maharishi Amrit Kalash-Ambrosia (MAK-A)
      and Maharishi Amrit Kalash-Nectar (MAK-N) are under investigation. This study
      shows that an ethanol extract of MAK-A induced morphological (neurite formation)
      and biochemical (increase of activity of tyrosine hydroxylase by about 15-fold)
      differentiation in murine neuroblastoma (NBP2) cells in culture, whereas an
      aqueous extract of MAK-A increased only the activity of tyrosine hydroxylase but
      to a much lesser extent. The treatment time of 3 days was needed for the
      expression of maximum differentiation. Ethanol extracts of MAK-A and aqueous
      extracts of MAK-A increased the intracellular level of adenosine 3',5'-cyclic
      monophosphate (cAMP) by about 4-fold in 3 days but they did not do so in 15 min.
      Ethanol extracts of MAK-A also induced neurite formation in neuroblastoma cells
      grown in serum free medium but the concentration requirement was about a fifth of
      that needed in serum. The treatment time of 24 hr was sufficient to induce
      optimal differentiation in neuroblastoma cells grown in serum free medium. The
      differentiating agents in ethanol-MAK-A were resistant to heat and light and
      could not be removed by treatment with activated charcoal. Neither ethanol-MAK-N
      nor aqueous-MAK-N induced differentiation in neuroblastoma cells, suggesting that
      the differentiating agents were present only in MAK-A.

PMID- 1357575
TI  - Effect of antidepressant drugs on monoamine synthesis in brain in vivo.
AB  - The activity of tryptophan and tyrosine hydroxylase were estimated in vivo by
      measuring the accumulation during 30 min of 5-hydroxytryptophan (5-HTP) and 3,4
      dihydroxyphenylalanine (DOPA), respectively, after inhibition of aromatic amino
      acid decarboxylase by administration of m-hydroxybenzylhydrazine (NSD 1015) (100
      mg/kg, i.p.). Whereas the activity of tyrosine hydroxylase in the dopamine-rich
      striatum was sensitive to haloperidol, which caused a significant increase in
      accumulation of DOPA, there was no effect of haloperidol in the predominantly
      noradrenergic frontoparietal cortex, confirming that the activity of tyrosine
      hydroxylase, measured in the frontoparietal cortex, is essentially localized in
      noradrenergic neurones. In the frontoparietal cortex of the rat the in vivo
      activity of tryptophan and tyrosine hydroxylase were equipotently attenuated by
      imipramine, while the selective blocker of the uptake of noradrenaline,
      desipramine and the selective blocker of the uptake of serotonin, citalopram,
      reduced only tyrosine or tyrosine hydroxylase respectively. Milnacipran, an
      antidepressant which inhibits the uptake of both monoamines to a similar extent,
      decreased the synthesis of both monoamines equipotently. The monoamine oxidase
      inhibitor, clorgyline, also reduced the synthesis of both monoamines. Thus, the
      in vivo inhibition of the synthesis of monoamines would appear to be mediated by
      an increase in synaptic concentration of monoamines, resulting from the
      inhibition of the uptake or catabolism of monoamines. Chronic administration of
      citalopram led to a significant increase of the basal synthesis of 5
      hydroxytryptamine (5-HT). Milnacipran, given chronically, significantly enhanced
      the basal synthesis of both 5-HT and noradrenaline (NA).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1357574
TI  - Stimulation of serotonin1A receptors increases release of prolactin in the rat.
AB  - The effect of serotonin1A receptor agonists on release of prolactin was examined
      in awake, freely-moving male rats in which a catheter in the jugular vein allowed
      samples of blood to be collected periodically after intravenous injection of the
      agonist. The serotonin1A receptor agonist, 8-hydroxy-2(di-n-propylamino) tetralin
      (8-OHDPAT) increased concentrations of prolactin in plasma rapidly and in a dose
      related manner. Concentrations of prolactin peaked within 9 min after intravenous
      injection of 8-OHDPAT and returned to baseline values within 30 min. Another
      serotonin1A receptor agonist, 5-methylurapidil (5-MeU), produced a similar
      response of prolactin. The effects of these agonists on release of prolactin were
      completely blocked by pretreatment with the serotonin receptor antagonists,
      methysergide and metergoline, administered 1 or 2 hr before the agonist. These
      results demonstrated that serotonin1A receptors can mediate the effects of
      serotonin on release of prolactin in the male rat.

PMID- 1357576
TI  - Differential development of tolerance to the depressant effects of benzodiazepine
      and non-benzodiazepine agonists at the omega (BZ) modulatory sites of GABAA
      receptors.
AB  - In a previous study, it was found that both the benzodiazepine hypnotic,
      midazolam, and the imidazopyridine hypnotic, zolpidem, which has selective
      affinity for a sub-population of omega (benzodiazepine, BZ) modulatory sites of
      GABA(A) receptors, produced similar decreases in rates of food-reinforced lever
      pressing in rats. However, during 10 days of repeated administration, marked
      tolerance developed to the depressant effect of midazolam but little tolerance
      developed with zolpidem. It was found in the present study that, with a within
      subject design similar to that used previously, tolerance developed to the
      response rate-decreasing activity of the benzodiazepine, triazolam and the
      cyclopyrrolone, zopiclone but not to that of the triazolopyridazine, CL 218,872.
      In another experiment, using a between-groups design, tolerance developed to the
      effect of midazolam, even if the injections were not associated with daily test
      sessions, providing no evidence for a drug-environment interaction. The lack of
      tolerance to zolpidem was confirmed in two experiments. There was little
      indication of tolerance to the depressant effect of zolpidem, even after 19 days
      administration of daily doses, up to 30 mg/kg, a dose 10 times greater than that
      which completely suppressed responding. These results showed that the extent to
      which tolerance develops to the effects of drugs with affinity for omega (BZ)
      modulatory sites can show wide variations which may be related to differences in
      mechanisms of action.

PMID- 1357577
TI  - The competitive NMDA antagonist CGP40.116 enhances L-dopa response in MPTP
      treated marmosets.
AB  - Experiments in MPTP-treated non-human primates testing potential antiparkinsonian
      action have shown both, beneficial and adverse effects of gutamate receptor
      antagonists. To investigate this matter further, the novel competitive NMDA
      antagonist CGP40.116 was administered systemically to three adult MPTP-treated
      marmosets. When coadministered subcutaneously with a subthreshold dose of L-DOPA,
      2 mg/kg, CGP40.116 25-250 micrograms/kg, increased locomotor activity. However,
      when administered alone, CGP40.116 had no effect on locomotor activity.

PMID- 1357578
TI  - Effect of noradrenergic denervation by neonatal DSP-4 on peptide neurotransmitter
      systems in the rat brain.
AB  - The specific effects of a neonatal treatment of rats with the noradrenergic
      neurotoxin DSP-4 were investigated in the adult rat by measuring monoamine and
      peptide transmitter levels in eight brain regions. When applied concomitantly
      with a 5-hydroxytryptamine uptake blocker, neonatal DSP-4 induced a selective
      depletion of noradrenaline (NA) in cortex, hippocampus and amygdala. An increase
      of NA was observed in the medulla and substantia nigra/ventral tegmental area and
      a decrease in dopamine was observed in the thalamus. The vasoactive intestinal
      polypeptide levels were markedly elevated in the DSP-4 treated rats in almost all
      CNS regions whereas those of three other neuropeptides remained unchanged. It is
      concluded that certain adaptational changes can be observed in the peptide
      systems of the CNS upon disruption of the development of the noradrenergic
      innervation.

PMID- 1357579
TI  - Suboccipital cerebrospinal fluid and plasma concentrations of somatostatin,
      neuropeptide Y and beta-endorphin in patients with common migraine.
AB  - The somatostatin-like (SLI), the neuropeptide Y-like (NPY-LI), and the beta
      endorphin-like (BE-LI) immunoreactivities of cerebrospinal fluid (CSF) obtained
      by suboccipital puncture, or plasma from patients suffering from common migraine
      or other neuropsychiatric disorders were analysed. The SLI concentration was
      tendentiously decreased in the migraine patients during the attack-free period
      compared to that of a 'mixed neuropsychiatric group'. During the migraine attack
      the level of SLI was further decreased. Similar alteration was found in the CSF
      BE-LI, while the BE-LI in the plasma showed only a tendentious decrease in common
      migraine patients. The NPY-LI did not change during the attack period in the CSF
      or plasma. These findings may indicate the possible role of somatostatin in the
      pathogenesis of common migraine, and support earlier observations that beta
      endorphin is involved in the development in this disorder.

PMID- 1357580
TI  - Somatostatin binding to a fresh rat astrocyte-enriched suspension.
AB  - Since there are conflicting reports regarding the effects of somatostatin (SS) on
      cyclic AMP levels in astrocytes derived from rat cerebral cortex and, to date,
      the SS binding to mature astrocytes is unknown, the present study has determined
      SS binding and its effect on cyclic AMP accumulation in a fresh astrocyte-rich
      suspension from rat cerebral cortex. 125I-Tyr11-SS binding was inhibited by SS in
      a dose-dependent manner. The Scatchard analysis of binding data was linear and
      yielded a dissociation constant of 0.95 +/- 0.15 nM with a maximal binding
      capacity of 122 +/- 13 fmol/mg protein. Vasoactive intestinal peptide (VIP)
      stimulated cyclic AMP accumulation up to 2.3 times above the basal levels whereas
      SS had no effect. This effect at any of the VIP concentrations. Likewise, SS did
      not inhibit the stimulation of cyclic AMP accumulation provoked by other
      effectors such as isoproterenol and forskolin. In view of our results and those
      of other authors, SS receptor localized in astrocytes must be able to couple with
      signal transduction systems other than adenylate cyclase, in order to carry out
      its biological actions in the cell.

PMID- 1357581
TI  - Somatostatin inhibition of VIP- and isoproterenol-stimulated cyclic AMP
      production in rat peritoneal macrophages.
AB  - The dual regulation of cyclic AMP levels in rat peritoneal macrophages incubated
      with somatostatin, vasoactive intestinal peptide (VIP), and isoproterenol was
      studied. Somatostatin exerted a non-competitive inhibition of the stimulatory
      effect of VIP and isoproterenol on cyclic AMP production. In addition,
      somatostatin inhibited basal cyclic AMP levels. Our results suggest that
      somatostatin and VIP may modulate the immune response acting, through cyclic AMP,
      on macrophage functions.

PMID- 1357582
TI  - Plasma free 3-methoxy-4-hydroxyphenylglycol in acute schizophrenics before and
      after treatment.
AB  - Plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) was measured in 19 patients
      with acute schizophrenia before and after neuroleptic therapy. Plasma
      antinoradrenergic activity (pANA) of the neuroleptics used was measured after
      treatment. Before treatment, pMHPG was higher in the patients than in 20 normal
      controls. There was a positive correlation between pMHPG level and the global
      severity of positive symptoms. After neuroleptic therapy, pMHPG was reduced, and
      there was a significant correlation between the decline in pMHPG and the
      improvement in positive symptom score. The decline in pMHPG was also correlated
      with pANA. These results suggest that there is a dysfunction of the noradrenergic
      system in the brains of some acute schizophrenics with mainly positive symptoms,
      and that this dysfunction may be improved, along with positive symptom score,
      after neuroleptic therapy.

PMID- 1357583
TI  - The rabbit syndrome and antiparkinsonian medication in schizophrenic patients.
AB  - Effects of antiparkinsonian medication on the rabbit syndrome (RS) and
      accompanying parkinsonian symptoms were studied in 5 schizophrenic inpatients
      receiving long-term antipsychotic medication. All patients showed early
      improvement of RS following additional treatment with trihexyphenidyl or
      biperiden, with a significant reduction in the RS score also observed. The
      improvement of RS paralleled improvement of the parkinsonian symptoms, with the
      score of the Simpson-Angus rating scale significantly reduced. Our data provide
      further evidence that the underlying mechanism of RS is similar to that of acute
      forms of drug-induced parkinsonism.

PMID- 1357584
TI  - Modulation of decay kinetics and frequency of GABAA receptor-mediated spontaneous
      inhibitory postsynaptic currents in hippocampal neurons.
AB  - Inhibitory postsynaptic currents mediated by spontaneous activation of GABAA
      receptors were studied using whole-cell voltage-clamp recordings in granule cells
      of the adult rat (postnatal day 60+) dentate gyrus in 400-microns-thick coronal
      half-brain slices maintained at 34-35 degrees C. The average amplitude of
      spontaneous inhibitory postsynaptic currents remained constant during a given
      recording period (i.e. no rundown was noted). The spontaneous currents had an
      average conductance between 200-400 pS, were mediated by Cl- flux through GABAA
      receptor/channels since they reversed at the Cl- equilibrium potential and were
      blocked by bicuculline or picrotoxin. Their mono-exponential decay time-constants
      (range: 4.2-7.2 ms) were prolonged by midazolam and pentobarbital in a dose
      dependent manner. The effect of midazolam was reversed by the benzodiazepine
      receptor antagonist flumazenil (RO 15-1788) which, by itself, had no effect on
      the decay time-constant. The decay time-constant was also dependent on membrane
      voltage and on temperature. A 132-mV change in membrane potential produced an e
      fold prolongation of the decay while the Q10 (between 22-37 degrees C) of the
      decay rate was 2.1. Within a given neuron, the frequency of spontaneous GABAergic
      events was remarkably constant over long time-periods, though the mean frequency
      among different cells showed large variability. Spontaneous miniature inhibitory
      postsynaptic currents also persisted under experimental conditions such as the
      presence of extracellular tetrodotoxin (1 microM), Cd2+ (200 microM) or lowered
      extracellular Ca2+/elevated Mg2+, which effectively abolished all stimulus-evoked
      GABAergic neurotransmission. The frequency of tetrodotoxin-resistant miniature
      events was increased by elevating extracellular K+ concentration and was
      diminished by the GABAB receptor agonist (-)baclofen only at a dose (50 microM)
      which was an order of magnitude larger than that required to depress stimulus
      evoked responses. These findings are consistent with different mechanisms being
      responsible for the spontaneous and stimulus-evoked release of GABA from
      interneuron terminals and also identify pre- and postsynaptic modulatory factors
      of the endogenous, action-potential-independent, GABAergic neurotransmission as
      being important determinants of the excitability level of mammalian CNS neurons.

PMID- 1357585
TI  - 5-(N-ethyl-N-isopropyl)amiloride and mild acidosis protect cultured cerebellar
      granule cells against glutamate-induced delayed neuronal death.
AB  - In the experiments on the primary cerebellar granule cell cultures, delayed
      neuronal death was induced by 15 min treatment of the cells with 50 microM
      glutamate. 5-(N-ethyl-N-isopropyl)amiloride (10 microM) known as a potent
      inhibitor of the Na+/H+ exchanger, when added to the glutamate-containing Mg(2+)
      free solution caused a considerable (approximately by 40%) decrease in the number
      of dead cells counted 4 h after the termination of glutamate treatment. Patch
      clamp experiments with freshly isolated rat hippocampal neurons have shown that
      the neuroprotective effect of 5-(N-ethyl-N-isopropyl)amiloride can be explained
      by its ability to block N-methyl-D-aspartate channels (receptors) at micromolar
      concentrations. A similar mechanism apparently underlies neuroprotective effect
      of external acidosis (reduction of pH from 7.6-7.8 to 6.7-6.8) during glutamate
      application. 5-(N-ethyl-N-isopropyl)amiloride (10 microM) and low pH (6.7) also
      proved capable of exhibiting neuroprotective effects upon application during the
      post-glutamate period. In this instance, however, the number of dead cells was
      decreased by no more than 20%. This neuroprotective effect of 5-(N-ethyl-N
      isopropyl)amiloride and low pH is interpreted as resulting from inhibition of
      Na+/H+ exchange, since a direct blockade of N-methyl-D-aspartate receptors by 1
      mM DL-2-amino-5-phosphonovalerate after termination of glutamate treatment did
      not attenuate the delayed neuronal death. Finally, we have established that the
      addition of 10 microM 5-(N-ethyl-N-isopropyl)amiloride to the cultures both
      during glutamate treatment and after its termination results in a complete
      protection of cultured cerebellar granule cells.

PMID- 1357586
TI  - Functional consequences of unilateral olfactory deprivation: time-course and age
      sensitivity.
AB  - Unilateral olfactory deprivation in the rat profoundly modifies olfactory bulb
      anatomy, chemistry and function. The present report examined the time-course of
      the functional effects of unilateral deprivation on inhibition in the olfactory
      bulb using paired-pulse stimulation of the lateral olfactory tract and olfactory
      nerve. In addition, an attempt was made to correlate these physiological measures
      with olfactory bulb dopamine and norepinephrine levels and tyrosine hydroxylase
      immunoreactivity. Deprivation from postnatal day 1 to postnatal day 20 or
      postnatal day 40 significantly enhanced lateral olfactory tract paired-pulse
      depression, while late onset deprivation (postnatal day 20) had no effect.
      Olfactory nerve paired-pulse depression was enhanced by 40 days of deprivation
      regardless of the age at onset. The time-course of these deprivation-induced
      physiological changes did not correlate well with reductions in dopamine.
      Dopamine levels were reduced in all deprivation conditions by 70-80% compared
      with control bulbs. Norepinephrine content was slightly elevated in deprived
      bulbs. These results suggest that early olfactory deprivation modifies olfactory
      bulb synaptic activity and further, as with other sensory systems, these effects
      are age and duration dependent.

PMID- 1357587
TI  - Relationship between dopamine release in the rat nucleus accumbens and the
      discharge activity of dopaminergic neurons during local in vivo application of
      amino acids in the ventral tegmental area.
AB  - Amino acids were pressure-ejected in the ventral tegmental area of rats which
      were anesthetized with chloral hydrate and treated with pargyline. The
      extracellular dopamine concentration was recorded from the nucleus accumbens with
      an electrochemically treated carbon fiber electrode combined either with
      differential normal pulse voltammetry or with differential pulse amperometry. In
      distinct rats the discharge activity of single dopaminergic neurons was monitored
      in the ventral tegmental area while amino acids were pressure-injected at a
      distance of 200-300 microns from the recorded cell. GABA (24 and 50 nl, 1 M)
      induced a complete and reversible inhibition of the firing rate lasting for 3-6
      min and a decrease in the basal extracellular dopamine level (-54% and -66%,
      respectively). Glutamate (32 nl, 10 mM), N-methyl-D-aspartate and quisqualate
      (100 microM) stimulated the firing rate and enhanced the dopamine extracellular
      concentration up to 10-times the basal one (18 nM). These increases subsided
      within 1-5 min. Their amplitude depended on the ejected volume (from 16 to 65
      nl). At the time-resolution of the method (some seconds) all these variations in
      the dopamine release appeared closely time-correlated with those of the firing
      rate. When the mean discharge rate is considered, N-methyl-D-aspartate was as
      potent as quisqualate but the former promoted burst firing while the latter
      induced a sustained activity. As regards dopamine release, N-methyl-D-aspartate
      was twice as potent as quisqualate. This further shows that dopaminergic
      terminals convert physiological impulse flow into dopamine release as a high pass
      filter which favors bursts of action potentials.

PMID- 1357588
TI  - N-methyl-D-aspartate receptor-independent long-term potentiation in area CA1 of
      rat hippocampus: input-specific induction and preclusion in a non-tetanized
      pathway.
AB  - We previously reported that an N-methyl-D-aspartate receptor-independent
      component of long-term potentiation with an apparent delayed onset can be induced
      in area CA1 of the hippocampus. Here we show that some but not all of this delay
      in onset can be accounted for by a transient heterosynaptic depression. We also
      show that N-methyl-D-aspartate receptor-independent long-term potentiation is
      induced only in the input pathway tetanized, and not in a second pathway.
      However, prior induction of N-methyl-D-aspartate receptor-independent long-term
      potentiation in one pathway precludes later induction in an independent pathway.
      Calcium entry through dihydropyridine-sensitive Ca2+ channels may be a critical
      step for induction of N-methyl-D-aspartate receptor-independent long-term
      potentiation in area CA1 [Grover L. M. and Teyler T.J. (1990) Nature 347, 477
      479]. Since the distribution [Westenbroek R. E. et al. (1990) Nature 347, 281
      284] of dihydropyridine-sensitive Ca2+ channels in CA1 neuron dendrites does not
      suggest a basis for input-specific induction of long-term potentiation, an
      additional process may confer the specificity we observed. Tetanic stimulation of
      afferents into area CA1 can elicit several processes: a transient heterosynaptic
      depression, and a transient homosynaptic potentiation, as well as N-methyl-D
      aspartate receptor-dependent and -independent long-term potentiation.

PMID- 1357589
TI  - Sulphur-containing excitatory amino acid-evoked Ca(2+)-independent release of D
      [3H]aspartate from cultured cerebellar granule cells: the role of glutamate
      receptor activation coupled to reversal of the acidic amino acid plasma membrane
      carrier.
AB  - Sulphur-containing excitatory amino acid transmitter candidates (500 microM)
      stimulated the Ca(2+)-independent efflux of exogenously-supplied D-[3H]aspartate
      from primary cultures of cerebellar granule cells superfused continuously with
      HEPES-buffered saline containing CoCl2 (1 mM) in place of CaCl2. The stimulated
      release of D-[3H]aspartate was markedly attenuated by 200 microM 6,7
      dinitroquinoxalinedione, a concentration at which the antagonist inhibits both
      non-N-methyl-D-aspartate and N-methyl-D-aspartate ionotropic excitatory amino
      acid receptors. The Ca(2+)-independent component of evoked release was also
      markedly attenuated and, in some cases, abolished by removing NaCl from the
      superfusion medium. Furthermore, when 700 microM dihydrokainate (demonstrated
      herein as a mixed/non-competitive inhibitor of the high-affinity dicarboxylic
      amino acid transporter in cultured granule cells) was included in the superfusion
      medium, stimulated efflux of D-[3H]aspartate was reduced by between 15-78% of the
      control response; the extent of inhibition varying with the agonist employed. In
      constrast, agents which act as competitive inhibitors of the plasma membrane
      carrier in granule cells, e.g. beta-methylene-D,L-aspartate, potentiated the
      release of D-[3H]aspartate in a synergistic manner. Taken together, these
      findings are consistent with a mechanism for the Ca(2+)-independent release of D
      [3H]aspartate that is mediated predominantly by activation of excitatory amino
      acid receptors resulting in a reversal of the high-affinity dicarboxylic amino
      acid transport system. Although the physiological relevance of such non-vesicular
      release from the cytosol remains obscure and is still a matter of some debate,
      this mode of release may be of pathological significance.

PMID- 1357590
TI  - A functional alpha-bungarotoxin receptor is present in chick cerebellum:
      purification and characterization.
AB  - It has recently been demonstrated that alpha-bungarotoxin receptors, which behave
      as functional nicotinic receptors, are present in chick CNS. In this paper, we
      report the purification and characterization of a functional alpha-bungarotoxin
      receptor from chick cerebellum, a nervous tissue in which a clear inhibition of
      induced nicotine effects has been reported in vivo. This receptor contains at
      least three subunits of apparent mol. wt 52,000, 57,000 and 67,000. The use of
      monoclonal antibodies specific for the alpha 7 subunit demonstrated that 75% of
      the molecules present in our purified preparation belong to the alpha 7 subtype
      and that this antibody labels the 57,000 band in western blot, thus indicating
      that this is the toxin binding subunit. Reconstruction experiments in planar
      lipid bilayers show that this alpha-bungarotoxin receptor forms a cation
      selective channel whose opening is blocked by d-tubocurarine. Binding experiments
      on immobilized receptors over an alpha-bungarotoxin-Sepharose affinity column
      show that the ligand binding subunit is present in vivo in two copies per
      receptor. Immunological, pharmacological and functional experiments show that
      this purified receptor is very similar, but not identical, to the previously
      characterized chick optic lobe receptor, thus indicating the heterogeneity of
      these alpha-bungarotoxin receptors in the CNS.

PMID- 1357591
TI  - Dopaminergic drugs reverse the impairment of radial-arm maze performance caused
      by lesions involving the cholinergic medial pathway.
AB  - Pharmacological studies have shown that both cholinergic and dopaminergic
      transmitter systems are crucial for optimal choice accuracy in the radial-arm
      maze and that these systems interact in a complex fashion. Lesion studies have
      provided evidence that the basal nuclear complex of the forebrain, the origin of
      cholinergic projections to the cerebral mantle, may be critical for the
      cholinergic modulation of learning and memory. We have shown that knife-cut
      lesions of the medial cholinergic pathway significantly impair radial-arm maze
      choice accuracy performance. The current study examined the effectiveness of D1
      and D2 ligands in counteracting this lesion-induced deficit. The adverse effects
      of medial cholinergic pathway lesions were diminished or reversed by daily
      treatment with a D1 agonist (SKF 38393), a D2 agonist (LY 171555) or a D1
      antagonist (SCH 23390), but were not affected by treatment with a D2 antagonist
      (raclopride). The three beneficial treatments have previously been found to
      attenuate the adverse effects of nictonic or muscarinic blockade on choice
      accuracy performance in the radial-arm maze. The finding that these dopaminergic
      drugs ameliorate the memory deficit caused by lesions involving the cholinergic
      medial pathway suggests the importance of interactions between cholinergic and
      dopaminergic systems in radial-arm maze performance. These results may provide
      leads for the development of novel therapeutic approaches for treating human
      disorders thought to result from cholinergic hypofunction.

PMID- 1357592
TI  - Repeated stimulation of D1 dopamine receptors causes time-dependent alterations
      in the sensitivity of both D1 and D2 dopamine receptors within the rat striatum.
AB  - Recent evidence suggests that repeated stimulation of D1 dopamine receptors
      within the rat striatum leads to an enhancement of both D1 and D2 dopamine
      receptor-mediated responses. The present study used both behavioral observations
      and extracellular single unit recording techniques to investigate this phenomenon
      following repeated administration of selective D1 dopamine receptor agonists.
      Groups of rats received twice daily administration of either saline or the
      partial D1 dopamine receptor agonist SKF 38393 (8 mg/kg, s.c.) for three weeks.
      Rats were tolerant to the ability of SKF 38393 to enhance grooming behavior when
      tested immediately following the last of the 42 treatment injections. However,
      the ability of this last SKF 38393 injection to potentiate oral stereotyped
      behavior following administration of the D2 DA agonist quinpirole was still
      evident. Following a one-day withdrawal, grooming responses to SKF 38393 had
      returned to normal. At this time, administration of quinpirole, without
      concomitant SKF 38393, failed to significantly promote oral stereotypies, as is
      typical of normal rats. Following a one-week withdrawal period, SKF 38393-induced
      grooming behavior was significantly enhanced and quinpirole, administered without
      SKF 38393, produced pronounced oral stereotyped behavior in 10 of 12 rats tested.
      Following a one-month withdrawal, these sensitized responses were no longer
      evident. Single-cell recordings from rat lateral striatal neurons revealed
      similar time-dependent alterations in the effects of iontophoretically
      administered SKF 38393 and quinpirole. Current-response curves revealed that,
      without a withdrawal period, striatal neurons were subsensitive to the inhibitory
      effects of SKF 38393 but not quinpirole. The decreased inhibitory responses of
      striatal neurons to SKF 38393 returned to normal levels after a one-day
      withdrawal. Following a one-week withdrawal, the effects of both agonists were
      significantly greater than that in saline-treated controls. Normosensitivity was
      evident following a one-month withdrawal. Repeated administration of the full D1
      DA agonist SKF 81297 (0.5 mg/kg, s.c., twice daily) also resulted in sensitized
      responses of striatal neurons following a one-week withdrawal, demonstrating that
      the sensitization to SKF 38393 was not due to its partial agonist character. The
      present findings provide both behavioral and electrophysiological evidence that
      repeated stimulation of D1 dopamine receptors results in a brief subsensitivity,
      followed by transient sensitization of the D1 receptors. The enhanced effects of
      D2 dopamine agonists might be due to an enhanced synergism (enabling) produced by
      endogenous dopamine stimulating supersensitive D1 receptors.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1357594
TI  - A PrP gene codon 178 base substitution and a 24-bp interstitial deletion in
      familial Creutzfeldt-Jakob disease.
AB  - Several mutations in the prion protein (PrP) gene are associated with familial
      Creutzfeldt-Jakob disease (FCJD). We describe a family in which five members in
      three generations have had FCJD. The proband and some descendants of the affected
      members carried an abnormal PrP gene allele. This allele contained a 24-bp
      deletion from the tandem repeat region of the open reading frame and a codon 178
      missense substitution. Observations suggest that the codon 178 mutation is
      involved in the pathogenesis of FCJD in the family described here. The 24-bp
      deletion may be an uncommon polymorphism.

PMID- 1357593
TI  - Analysis of the prion protein gene in thalamic dementia.
AB  - Thalamic degenerations or dementias are poorly understood conditions. The
      familial forms are (1) selective thalamic degenerations and (2) thalamic
      degenerations associated with multiple system atrophy. Selective thalamic
      degenerations share clinical and pathologic features with fatal familial
      insomnia, an autosomal dominant disease linked to a mutation at codon 178 of the
      prion protein (PrP) gene that causes the substitution of asparagine for aspartic
      acid (178Asn mutation). We amplified the carboxyl terminal coding region of the
      PrP gene from subjects with selective thalamic dementia or thalamic dementia
      associated with multiple system atrophy. Three of the four kindreds with
      selective thalamic dementia and none of the three kindreds with thalamic dementia
      associated with multiple system atrophy had the PrP 178Asn mutation. Thus,
      analysis of the PrP gene may be useful in diagnosing the subtypes of thalamic
      dementia. Moreover, since selective thalamic dementia with the PrP 178Asn
      mutation and fatal familial insomnia share clinical and histopathologic features,
      we propose that they are the same disease.

PMID- 1357595
TI  - Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and
      treatment of a new inborn error of neurotransmitter amine synthesis.
AB  - We report the clinical features, biochemical details, and treatment of the first
      detected cases of an inborn error of aromatic L-amino acid decarboxylase. Male
      monozygotic twins presented with extreme hypotonia and oculogyric crises.
      Concentrations of biogenic amines and their metabolites were reduced considerably
      both centrally and peripherally. Pterin and phenylalanine metabolism were normal.
      Activity of aromatic L-amino acid decarboxylase was virtually absent in a liver
      biopsy sample and greatly reduced in plasma. Concentrations of L-dopa, 3
      methoxytyrosine, and 5-hydroxytryptophan were elevated in CSF, plasma, and urine.
      CSF S-adenosylmethionine concentrations were reduced. Pyridoxine treatment had no
      clinical effect but led to a fall in CSF L-dopa and 3-methoxytyrosine and a rise
      in S-adenosylmethionine. Treatment with either bromocriptine or tranylcypromine
      stopped the abnormal eye movements; tranylcypromine treatment also improved
      muscle tone and led to a rise in plasma norepinephrine and whole blood serotonin.
      Combined treatment with pyridoxine, bromocriptine, and tranylcypromine produced
      sustained improvement in tone and voluntary movements. The twins' parents were
      asymptomatic but had reduced plasma aromatic L-amino acid decarboxylase activity,
      consistent with heterozygosity. We monitored a subsequent pregnancy through
      biochemical analyses of a fetal liver biopsy sample and of amniotic fluid. We
      predicted an unaffected fetus, which was confirmed clinically and biochemically
      after birth.

PMID- 1357596
TI  - Hyperammonemic alterations in the metabolism of glutamate and aspartate in rat
      cerebellar astrocytes.
AB  - Pathophysiological concentrations of ammonia, both in vivo and in vitro,
      suppressed the production of 14CO2 from 14C-labelled glutamate and aspartate in
      astrocytes isolated from the rat cerebellum. Suppression of 14CO2 production with
      (aminooxy)acetic acid but not with glutamic acid diethyl ester indicated that
      transamination plays a major role in the oxidation of glutamate carbons.
      Activities of the enzymes, aspartate amino-transferase, alanine aminotransferase
      and glutaminase were decreased while those of glutamate dehydrogenase and
      glutamine synthetase were enhanced in the cerebellar astrocytes during
      hyperammonemic states. These results suggest an impairment of astrocytic
      glutamate metabolism during hyperammonemia.

PMID- 1357597
TI  - The selective A2 adenosine receptor agonist CGS 21680 enhances excitatory
      transmitter amino acid release from the ischemic rat cerebral cortex.
AB  - The effects of the selective adenosine A2 receptor agonist 2-p-(2
      carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride (CGS
      21680) on aspartate and glutamate release from the ischemic rat cerebral cortex
      were studied with the cortical cup technique. Cerebral ischemia (20 min) was
      elicited by four vessel occlusion. Pretreatment with CGS 21680 failed to alter
      basal excitatory amino acid levels, however, CGS 21680 at 10(-6) M significantly
      enhanced the ischemia-evoked release. Thus, aspartate and glutamate release
      during ischemia can be stimulated via the activation of A2 receptors, in addition
      to the suppression of excitatory amino acid release mediated by selective A1
      receptor agonists.

PMID- 1357598
TI  - Mossy fiber long-term potentiation shows specificity but no apparent
      cooperativity.
AB  - Specificity in long-term potentiation (LTP) means that synapses onto a
      postsynaptic cell can potentiate independently of one another. Cooperativity
      refers to a requirement that some threshold number of afferents be co-activated
      to evoke LTP with a high-frequency stimulus. The induction of long-term
      potentiation (LTP) at the associational/commissural synapses onto hippocampal CA3
      pyramidal cells shows clear cooperativity. LTP of mossy fiber inputs to these
      cells does not. Mossy fiber LTP does show synapse specificity. These results bear
      on the cellular mechanisms and the functions of mossy fiber LTP.

PMID- 1357599
TI  - Effects of pretreatment with sublethal ischemia on the extracellular glutamate
      concentrations during secondary ischemia in the gerbil hippocampus evaluated with
      intracerebral microdialysis.
AB  - To elucidate the role of glutamate in the pathogenesis of altered neuronal
      vulnerability following sublethal ischemia, we measured the extracellular
      concentrations of glutamate in the gerbil hippocampus using a microdialysis
      technique. During and immediately after 3-min forebrain ischemia, the
      extracellular glutamate level showed a striking increase. However, pretreatment
      with 2-min ischemia 1 h or 4 days before secondary 3-min ischemia did not alter
      the amount of glutamate released. The result indicates that cumulative damage and
      tolerance, which take place after pretreatment with sublethal ischemia, are not
      induced through modification of the amount of glutamate released during secondary
      ischemia.

PMID- 1357600
TI  - Changes in hippocampal acetylcholine and glutamate extracellular levels during
      soman-induced seizures: influence of septal cholinoceptive cells.
AB  - The changes in extracellular acetylcholine and glutamate levels were determined,
      during the course of seizures induced by soman, an irreversible inhibitor of
      acetylcholinesterase, in the CA1 hippocampal area of rats previously injected
      with atropine or normal saline into septum. The marked increases observed in
      soman-treated animals were abolished in rats receiving atropine. These data
      strongly suggest that, during soman intoxication, septal cholinoceptive cells
      play a key role in controlling the release of acetylcholine and glutamate in
      hippocampus. The mechanisms underlying this phenomenon are discussed.

PMID- 1357601
TI  - Comparative neurotoxic potential of glutamate, endothelins, and platelet
      activating factor in cerebral cortical cultures.
AB  - The excitatory amino acid glutamate, the peptides endothelin-1 and -3, and the
      phospholipid platelet-activating factor have been implicated in ischemic injury
      to the nervous system. To determine if, like glutamate, endothelins and platelet
      activating factor are directly toxic to neurons, we examined their effects on
      lactate dehydrogenase release and trypan blue dye exclusion in rat cerebral
      cortical cultures. Glutamate (1 mM) increased lactate dehydrogenase release by
      approximately 75% and reduced the number of cells excluding trypan blue dye by
      approximately 50%. In contrast, endothelins (0.5 and 100 nM) and platelet
      activating factor (0.1 and 10 microM) had no effect on these indices of cell
      injury. Endothelins and platelet-activating factor appear more likely to act on
      blood vessels than on neurons or glia as mediators of ischemic injury.

PMID- 1357602
TI  - Production of seizures and brain damage in rats by alpha-dendrotoxin, a selective
      K+ channel blocker.
AB  - alpha-Dendrotoxin (Dtx), a snake polypeptide, increases neuronal excitability by
      blocking certain fast-activating, voltage-dependent K+ channels. Thus, the
      behavioural, electrocortical (ECoG) and neuropathological effects of Dtx,
      injected into rat brain areas, were studied. A unilateral injection of 35 pmol of
      Dtx into the CA1 hippocampal area or the dendate gyrus (DG; upper blade)
      immediately produced motor and ECoG seizures, followed at 24 h by multi-focal
      brain damage and significant neuronal loss. Whilst brain damage was seen
      bilaterally, significant neuronal loss occurred only in regions (CA1, CA3, CA4
      and DG) ipsilateral to the site of injection. A lower dose (3.5 pmol) of toxin
      elicited motor and ECoG seizures but failed to produce brain damage. Seizures
      were observed 50 min after injecting Dtx (35 pmol) into the amygdala, though
      significant neuronal loss was not evident. 4-Aminopyridine (100 nmol), given into
      the CA1 area elicited a similar motor and ECoG pattern to that of Dtx except no
      brain damage could be seen at 24 h. Systemic pretreatment with antagonists of N
      methyl-D-aspartate receptors (MK-801 or CGP 37849) did not protect against the
      effects typically evoked by injecting Dtx into the CA1 area.

PMID- 1357603
TI  - Activation of quisqualate metabotropic receptors reduces glutamate and GABA
      mediated synaptic potentials in the rat striatum.
AB  - The role of quisqualate (QUIS) metabotropic receptors in the synaptic
      transmission in the striatum was investigated using the cortico-striatal slice
      preparation. Low concentrations (1-30 microM) of trans-1-amino-cyclopentyl-1,3-
      dicarboxylic acid (t-ACPD), a selective agonist of QUIS metabotropic receptors,
      decreased glutamate-mediated synaptic potentials (EPSPs) evoked in the striatum
      by the stimulation of cortico-striatal fibers. This agonist decreased also GABA
      mediated depolarizing synaptic potentials evoked by intrastriatal stimulation in
      the presence of 6-cyano-7-nitro-quinoxaline-2,3- dione (CNQX); this effect was
      less potent than the action of t-ACPD on glutamate-mediated potentials. Low
      concentrations of t-ACPD did not affect the intrinsic membrane properties of
      striatal neurons and their postsynaptic responses to exogenous glutamate and
      GABA. Higher concentrations (50-100 microM) to t-ACPD caused membrane
      depolarizations and inward currents in several neurons. Our data suggest that low
      concentrations of t-ACPD selectively reduce synaptic transmission while higher
      concentrations of this agonist may cause a direct excitatory action on striatal
      neurons.

PMID- 1357604
TI  - Alpha 2-adrenoceptor modulation of 5-HT biosynthesis in the rat brain.
AB  - The purpose of the present study is to clarify the modulation of the biosynthesis
      of serotonin (5-HT) via the alpha 2-adrenoceptors in the brain. For this purpose,
      5-hydroxytryptophan (5-HTP) accumulation was determined using an HPLC-ECD system
      in the presence of the inhibition of aromatic L-amino acid decarboxylase.
      Administration of alpha 2-adrenoceptor agonist, clonidine, produced a reduction
      of the in vivo 5-HTP accumulation in both the rat hippocampus and dorsal raphe
      nucleus. In addition, alpha 2-adrenoceptor antagonist, idazoxan, increased the 5
      HTP accumulation in both the hippocampus and the dorsal raphe nucleus. In rats
      with catecholaminergic neurons denervated by pretreatment with 6-hydroxydopamine,
      clonidine failed to produce a reduction of 5-HTP accumulation in the dorsal raphe
      nucleus. On the other hand, hippocampal 5-HTP accumulation was decreased
      significantly. Brain tryptophan levels were unaffected by either clonidine or
      idazoxan. These results suggest that alpha 2-adrenoceptors might modulate
      serotonin biosynthesis and this modulation might be related to the
      neuroanatomical differences in the rat brain.

PMID- 1357605
TI  - Evidence for the involvement of the mu but not delta opioid receptor subtype in
      the synergistic interaction between opioid and alpha 2 adrenergic antinociception
      in the rat spinal cord.
AB  - The interaction between the spinal antinociceptive effects of selective mu or
      delta opioid agonists morphine and DSTBULET (Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr),
      respectively, and the selective alpha 2 adrenergic agonist dexmedetomidine was
      examined on convergent dorsal horn neuronal responses in the intact anaesthetized
      rat. The coadministration of intrathecal morphine (0.5 microgram, 2.5 micrograms)
      and dexmedetomidine (0.5 microgram) produced a greater than additive inhibition
      of C fibre-evoked responses. Inhibitions were reversed by either the opioid
      antagonist naloxone or the alpha 2 adrenergic antagonist atipamezole. The
      coadministration of intrathecal DSTBULET (1 microgram, 2.5 micrograms) and
      dexmedetomidine did not result in a supra-additive inhibition of C fibre-evoked
      responses. The results suggest that mu rather than delta opioid receptors are
      involved in the synergism of spinal opioid and alpha 2 adrenergic
      antinociception.

PMID- 1357606
TI  - Excitatory effect of N-methyl-D-aspartate and kainate receptor on the 2
      deoxyglucose uptake in the rat suprachiasmatic nucleus in vitro.
AB  - The suprachiasmatic nuclei (SCN) have been identified as a pacemaker for many
      circadian rhythms in mammals. The previous findings indicate the excitatory amino
      acid (EAA) receptors play an important role in the transmission of light
      information from the retina to the circadian clocks. The 2-deoxyglucose (2DG)
      uptake shows a robust circadian change; high uptake during subjective day and low
      uptake subjective night. To determine whether EAA agonists regulate 2DG uptake in
      the SCN, we have measured 2DG uptake in the rat SCN in vitro. We report that,
      during the subjective night, glutamate, N-methyl-D-aspartate (NMDA) and kainic
      acid (KA) cause an increase in 2DG uptake and that NMDA- or KA-induced increase
      of 2DG uptake is blocked by co-treatments with competitive and non-competitive
      NMDA or KA receptor antagonists. EAA receptor agonist-induced increase in 2DG
      uptake occurs only during subjective night, at circadian times when photic phase
      shifting of activity occurs. Taken together, those data suggest that EAA may be
      an important transmitter of light information from retina to the SCN.

PMID- 1357607
TI  - Trans-ACPD and L-APB presynaptically inhibit excitatory glutamatergic
      transmission in the basolateral amygdala (BLA).
AB  - Intracellular recordings were obtained from neurones of the basolateral nucleus
      of the amygdala (BLA) and glutamate-mediated EPSPs evoked by stimulation of the
      stria terminalis (ST). The conformationally restricted analogue of glutamate
      trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) caused a dose
      dependent reduction in EPSP amplitude, EC50 approximately 50 microM. This effect
      was mimicked by the glutamate autoreceptor agonist, L-aminophosphonobutyric acid
      (L-APB, 50 microM). Furthermore, the effects of submaximal concentrations (50
      microM) of trans-ACPD and L-APB were additive. The reduction in EPSP amplitude is
      observed with concentrations of both drugs that have no effect on either the
      resting membrane potential or the input resistance of BLA neurones. In addition,
      these compounds can reduce EPSP amplitude but not the response to exogenous
      application of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionate (AMPA)
      suggesting activation of presynaptic receptors. These findings suggest that both
      trans-ACPD and L-APB act at presynaptic glutamate receptors on glutamatergic
      afferents to reduce excitatory transmission in the BLA.

PMID- 1357608
TI  - Dynorphin, a preferential ligand for kappa-opioid receptors, is present in nerve
      fibers and immune cells within inflamed tissue of the rat.
AB  - Exogenous kappa-opioid agonists have been shown to produce peripheral
      antinociceptive effects in inflamed tissue. This study sought to determine
      whether endogenous kappa-receptor ligands are present at the site of
      inflammation. In Freund's adjuvant-induced hindpaw inflammation in the rat, we
      show, by immunohistochemistry, that dynorphin is detectable within inflammatory
      cells and in the cutaneous nerves in a similar distribution as calcitonin gene
      related peptide, a specific marker for sensory neurons. These findings extend our
      previous observations in that not only beta-endorphin and Met-enkephalin (mu- and
      delta-receptor ligands), but also a preferential kappa-ligand is present within
      inflamed subcutaneous tissue.

PMID- 1357609
TI  - Dopamine D1 and D2 receptor interactions in the MPTP-treated marmoset.
AB  - In a modified MPTP model of Parkinson's disease in the marmoset, both L-DOPA and
      the dopamine D2 agonist quinpirole were found to exhibit anti-bradykinetic
      activity. Both the dopamine D1 agonist SKF38393 and the D1 antagonist SCH23390
      reduced the anti-bradykinetic action of L-DOPA and quinpirole. These results are
      discussed with respect to partial agonist activity of SKF38393 and the
      possibility that other dopamine receptors may be required for anti-Parkinsonian
      drug activity.

PMID- 1357610
TI  - Loss of high-affinity alpha 2-adrenoceptors in Alzheimer's disease: an
      autoradiographic study in frontal cortex and hippocampus.
AB  - We assessed, by quantitative autoradiography, the density of high-affinity alpha
      2-adrenoceptors in hippocampus and frontal cortex sections from 18 patients dying
      with Alzheimer's disease (AD) in comparison with a control group of 13 matched
      cases. The full agonist [3H]bromoxidine (UK-14304) was used as a ligand. In AD
      brains, the specific binding of [3H]bromoxidine was markedly decreased both in
      frontal cortex, the reduction ranging from 55% on layer I (P less than 0.0005) to
      40% loss on layers IV-VI (P less than 0.01), and in the hippocampus where the
      mean of alpha 2-receptor loss was 53% both for the CA1 (P less than 0.0005) and
      the dentate gyrus (P less than 0.005). This dramatic decrease in the density of
      functional, high-affinity alpha 2-adrenoceptors very probably reflects the
      neuronal loss described in locus coeruleus of AD brains. The important
      implications of these findings for the pharmacological treatment of AD are
      discussed.

PMID- 1357611
TI  - Coactivation of D1 and D2 dopamine receptors is required for long-term synaptic
      depression in the striatum.
AB  - Long-term changes of synaptic transmission following brief trains of high
      frequency stimulation of excitatory pathways in the brain have attracted
      attention as a possible correlate of memory. In the cerebellum, concurrent
      activation of parallel fibers and climbing fibers leads to a long-term depression
      (LTD) of synaptic transmission, which may be the cellular substrate of motor
      learning in this structure. We report here for the first time that high-frequency
      stimulation of corticostriatal glutamatergic fibers in the striatum, another
      brain structure strongly involved in motor control, also induces LTD of synaptic
      transmission. Induction of striatal LTD is blocked either by SCH 23390, a D1
      dopamine (DA) receptor antagonist or by L-sulpiride, a D2 DA receptor antagonist.
      The lesion of the nigrostriatal DAergic pathway abolishes LTD. After DA
      depletion, LTD can be restored by the application of exogenous DA. LTD can also
      be restored by coadministration of D1 and D2 DA receptor agonists, but not by the
      application of a single class of DA agonists alone. Our data show that
      coactivation of D1 and D2 DA receptors is required for LTD in the striatum. D1/D2
      receptor cooperation in the induction of LTD may play a crucial role in the
      behavioural function of DA and in the therapeutic effects of DA agonists in
      Parkinson's disease.

PMID- 1357613
TI  - Proceedings of Interdisciplinary Symposium on Gene, Nutrition and Health. Kobe,
      Japan, October 1st, 1991.

PMID- 1357612
TI  - Anterograde amnesia linked to benzodiazepines.
AB  - Benzodiazepines, shown to affect memory, can produce anterograde amnesia (i.e., a
      loss of memory for events occurring forward in time). Following the ingestion of
      a benzodiazepine, short-term memory is not affected, but long-term memory is
      impaired. The memory loss may occur because events are not transferred from short
      term memory to long-term memory and thus not consolidated into memory storage.
      Information stored prior to the ingestion of a benzodiazepine is not affected.
      Memory impairment is more likely in benzodiazepines that have a high
      benzodiazepine-receptor affinity, that accumulate in the body, that are given in
      high doses or intravenously, or that are eliminated slowly. Individuals taking
      benzodiazepines are often unaware of their memory impairment unless it is pointed
      out to them. Elderly clients experiencing memory impairment may be embarrassed to
      mention the problem. Alternatives to prescribing benzodiazepines include
      antidepressant medications, exercise or psychotherapy. When prescribing a
      benzodiazepine, it is important to fully inform patients of the drug's potential
      side effects and to maintain the lowest effective dose for the shortest period of
      time.

PMID- 1357614
TI  - Intercellular adhesion molecule-1 (ICAM-1) and HLA-DR antigens in herpes
      keratitis.
AB  - PURPOSE: Intercellular adhesion molecule-1 (ICAM-1) is a cell surface
      glycoprotein that binds leukocyte function antigen-1 receptor on leukocytes,
      thereby regulating leukocyte trafficking and function at sites of inflammation.
      Recently, the authors demonstrated ICAM-1 in human corneas exposed to
      proinflammatory cytokines, but ICAM-1 has not been reported in corneal disease.
      In this study, the presence of ICAM-1 in human disciform herpes simplex virus
      (HSV) keratitis is investigated. METHODS: Immunohistochemistry was performed for
      ICAM-1 on 4 keratoplasty specimens from patients with corneal scarring due to
      disciform HSV keratitis and 1 corneoscleral biopsy of a patient with active HSV
      keratoscleritis using specific, characterized monoclonal antibody to ICAM-1.
      Negative immunohistochemical controls included monoclonal antibodies to other
      vascular endothelial adhesion molecules or mouse serum. RESULTS: All 5 specimens
      demonstrated intense ICAM-1 immunoreactivity of keratinocytes, stromal
      keratocytes, and endothelial cells, predominantly in regions of leukocytic
      infiltration. Diffuse, intense HLA-DR positivity was detected throughout the
      corneas. The specimens failed to react with control antibodies. CONCLUSION: These
      results are the first to demonstrate ICAM-1 in human corneal disease and suggest
      important roles for ICAM-1 and HLA-DR co-expression in generating immune
      responses in HSV keratitis. Increased ICAM-1 expression in regions of leukocytic
      infiltration may regulate leukocyte-corneal cell binding, thereby promoting
      immune responses and damage by activated leukocytes.

PMID- 1357615
TI  - Ocular jellyfish stings.
AB  - BACKGROUND: Corneal stings from the sea nettle (Chrysaora quinquecirrha)
      indigenous to the Chesapeake Bay are usually painful but self-limited injuries,
      with resolution in 24 to 48 hours. METHODS: Five patients who developed unusually
      severe and prolonged iritis and intraocular pressure elevation after receiving
      corneal sea nettle stings were followed for 2 to 4 years. RESULTS: Decreased
      visual acuity, iritis, and increased intraocular pressure (32 to 48 mmHg) were
      noted in all cases. Iritis responded to topical corticosteroids and resolved
      within 8 weeks. Elevated intraocular pressure responded to topical beta blockers
      and oral carbonic anhydrase inhibitors. Mydriasis (4 of 5 cases), decreased
      accommodation (2 of 5 cases), peripheral anterior synechiae (2 of 5 cases), and
      iris transillumination defects (3 of 5 cases) also were noted. Mydriasis and
      decreased accommodation persisted for 5 months in 1 case and for more than 2
      years in another. One patient has chronic unilateral glaucoma. Visual acuity
      returned to normal in all cases. CONCLUSIONS: The precise relationship between
      sea nettle venom and the observed clinical responses is not known. Corneal
      jellyfish stings usually produce a brief and self-limited reaction, but they do
      have the potential for long-term sequelae.

PMID- 1357616
TI  - Neurotransmission in the auditory system.
AB  - Neurotransmitters and neuromodulators thought to be active on neurons in the
      cochlea, CN, and SOC have been reviewed. The variety of neurotransmitters and
      neuromodulators present and likely colocalized in these neurons are the chemical
      substrates that link morphologically and physiologically diverse neurons to
      process sound information. The impact of the limited number of neurotransmitters
      and neuromodulators in the auditory system is magnified by their interaction with
      structurally diverse receptors; thus great functional diversity is possible.
      Moreover, the effects of neurotransmitters and neuromodulators are not limited to
      synaptic transmission but serve as trophic agents for the establishment of
      neuronal circuitry during development and the rearrangement of synapses as a
      result of sensory experience or injury. An understanding of the neurochemical
      aspects of sensory processing at these diverse synapses then is of fundamental
      importance in understanding the organization of the auditory system.

PMID- 1357617
TI  - In situ hybridization for the localization of gene products in the auditory
      system.
AB  - In this article, an overview of the technique and examples of our data
      demonstrate that our protocols produce excellent, reliable in situ hybridization
      of mRNAs and immunohistochemical localization of mRNA translation products in the
      temporal bone and brain stem. This in situ hybridization protocol has been used
      to localize eight different mRNAs, including four types of nicotinic
      acetylcholine receptor subunit mRNAs, actin mRNA, CGRP mRNA, and two mRNAs coding
      for gap junction proteins, in both paraffin-embedded and sectioned (6 microns)
      and cryostat sectioned (15 microns) temporal bones (unpublished data). In
      conclusion, in situ hybridization of mRNAs with single-stranded RNA probes allows
      screening of brain stem and temporal bone sections for the expression of specific
      genes, with cellular resolution, and this protocol gives reliable results for all
      mRNAs studied. Of great potential significance is the ability to assess
      variations in gene expression by in situ hybridization of specific mRNAs. It is
      expected that such variations accompany changes in the physiologic state of an
      organism, such as developmental, pathologic or experimentally induced, and that
      these variations in gene expression are important in understanding basic auditory
      processes at the cellular level.

PMID- 1357618
TI  - Molecular biology and genetics for the otolaryngologist--head and neck surgeon.

PMID- 1357619
TI  - Systemic injections of alpha-1 adrenergic agonists produce antinociception in the
      formalin test.
AB  - The role of alpha 1 receptors in antinociception was investigated in the formalin
      test, a well established test of tonic pain. The effect of systemic injections of
      selective alpha 1-adrenergic agonists (phenylephrine and methoxamine), a mixed
      alpha agonist selective for alpha 2 receptors (ST-91), and 2 adrenergic
      antagonists (prazosin and idazoxan) was measured in groups of Long-Evans rats.
      All agonists tested produced significant antinociception in this test. Dose
      response curves for each agonist were statistically parallel and equally
      efficacious (100% antinociception). Prior injection of 0.15 mg/kg prazosin (an
      alpha 1 antagonist) completely antagonized the antinociception produced by either
      an ED50 or a maximally effective dose of each agonist tested. Idazoxan (0.5
      mg/kg), an alpha 2 antagonist, was without effect on the antinociception produced
      by phenylephrine or methoxamine. ST-91 produced significant antinociception in
      the presence of idazoxan although the response was different from that obtained
      with ST-91 alone. The observed antinociception in the formalin test was not due
      to drug-induced changes in peripheral inflammation as measured using
      plethysmometry. Moreover, none of the drugs tested produced significant changes
      in coordinated motor behavior (accelerated rotarod test) at doses that produced
      significant analgesia (ED50). We conclude that alpha 1 receptors contribute
      significantly to adrenergic analgesia in the formalin test by an undefined action
      on sensory processing mechanisms.

PMID- 1357620
TI  - Reduction in adherence of Actinomyces viscosus after exposure to low-frequency
      acoustic energy.
AB  - The ability of low-frequency (200 Hz) acoustic energy to reduce the adherence of
      Actinomyces viscosus T14V to saliva-treated hydroxyapatite (SHA) disks was
      studied. An acoustic pressure range between 0 and 65 kPa and exposure durations
      between 0 and 8 min were used to study the levels necessary to significantly
      alter adherence. The effects of acoustic exposure on both bacteria in liquid and
      bacteria already adhering to SHA disks were studied. A modified enzyme-linked
      immunosorbent assay was used to assess bacterial adherence. For bacterial
      suspensions exposed prior to addition to SHA disks, it was found that reductions
      in adherence were greater for lower bacterial concentrations. Exposure of
      bacteria already adhering to SHA disks resulted in a decrease in adherence that
      was independent of the bacterial concentration and linearly related to the
      logarithm of the exposure duration. In addition to affecting adherence, acoustic
      energy also dispersed bacterial aggregates. Our results support the concept that
      low-frequency sonic energy applied orally may be of therapeutic value in reducing
      adherence and colonization of teeth by plaque bacteria.

PMID- 1357623
TI  - The proper role of beta 2-adrenergic agonists in the treatment of children with
      asthma.

PMID- 1357621
TI  - [Insulin sensitivity during use of adrenoblockers and adrenomimetics].
AB  - The effect of adrenergic blocking agents and adrenomimetics on sensitivity to
      insulin was studied in rat experiments. The sensitivity was judged from the
      duration of hypoglycemic coma development after intravenous infusion of 40 U/kg
      insulin. Sensitivity to insulin increased with the beta-adrenergic blocking agent
      obsidan and the alpha-adrenomimetic mesaton (phenylephrine hydrochloride) but
      diminished after infusion of the beta-adrenomimetic partusisten and the alpha
      adrenergic blocking agent butyroxane. The obtained data are discussed from the
      standpoint of insulin-resistance control.

PMID- 1357622
TI  - Characterization of the beta-adrenergic receptor in isolated human fetal lung
      type II cells.
AB  - Functioning of the beta-adrenergic response system is important for successful
      transition of the neonate from fetal life to breathing air. We characterized the
      beta-adrenergic receptors on human fetal lung type II cells, the cell type
      responsible for many pulmonary responses sensitive to beta-adrenergic
      stimulation. Type II cells were isolated from human fetal lung explants, and
      membrane particulates prepared from these cells were used for radioligand binding
      studies. 125I-iodocyanopindolol, a specific beta-adrenergic antagonist, bound to
      a single class of saturable, high-affinity binding sites on type II cell
      membranes with a receptor concentration of 78 +/- 9 fmol receptor/mg membrane
      protein, a kd of 79 +/- 18 nM, and 958 +/- 120 receptors per cell. Binding was
      stereoselective with l-propranolol binding with higher affinity than the inactive
      d-isomer. The binding site had the characteristics of a beta 2-adrenergic
      receptor. The order of potency of beta-adrenergic agonists was isoproterenol
      greater than epinephrine much greater than norepinephrine. The beta 2-selective
      antagonist ICI 118,551 competed for a single class of high-affinity sites.
      Agonist binding affinity was reduced in the presence of guanyl nucleotides,
      consistent with receptors coupled to guanine nucleotide binding proteins. beta
      Adrenergic agonists also stimulated adenylyl cyclase in these membrane
      preparations. 125I-iodocyanopindolol binding to membranes prepared from human
      fetal lung fibroblasts indicated fewer receptors (404 +/- 68) than were present
      on type II cells. Work by others has suggested a difference in lung function and
      lung beta-adrenergic receptor concentration between males and females.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1357624
TI  - 1st European Congress of Pharmaceutical Sciences. Amsterdam, The Netherlands, 7-9
      October 1992. Abstracts.

PMID- 1357625
TI  - Dopamine inhibits Na/K-ATPase in single tubules and cultured cells from distal
      nephron.
AB  - Dopamine decreases tubular sodium reabsorption, attributed in part to Na/K-ATPase
      inhibition in the proximal convoluted tubule (PCT). Because the final regulation
      of sodium excretion occurs in the collecting duct, where we have demonstrated
      specific dopamine DA1 binding sites, we examined the effects of dopamine, and of
      DA1 and DA2 receptor agonists on the Na/K pump in the microdissected rat cortical
      collecting duct (CCD) and in Madin-Darby canine kidney (MDCK) cells, a line
      derived from the dog distal nephron. Dopamine inhibited pump activity in CCD by
      approximately 40%-50%, an effect proportionally larger than in the PCT. Unlike in
      the latter, the effect of dopamine was reproduced by the DA1 agonist fenoldopam,
      which inhibited the CCD pump in dose-dependent manner (maximum, 10 microM). The
      DA2 agonist quinpirole was without effect, either alone or in combination with
      fenoldopam. These actions on Na/K-ATPase paralleled in reciprocal fashion effects
      on adenylate cyclase: dopamine or fenoldopam, but not quinpirole, produced a
      significant increase in cAMP content, and the stimulation by dopamine was blocked
      by SCH 23390. Inhibitors of cAMP phosphodiesterase (3-isobutyl-1-methyl-xanthine
      and theophylline), as well as forskolin and dibutyryl-cAMP, mimicked the effect
      of dopamine on the pump, underscoring the role of increased cAMP in this
      phenomenon. Both dopamine and fenoldopam inhibited Na/K-ATPase activity in MDCK
      cells. The results indicate that besides the PCT dopamine inhibits Na/K-ATPase
      activity in cells of the distal nephron, where its effect on the pump appears to
      be more pronounced and is mediated by activation of the DA1 receptor. The
      natriuretic effect of dopamine is probably exerted at both proximal and distal
      nephron sites.

PMID- 1357627
TI  - Transplantation of umbilical cord blood in neuroblastoma.
AB  - It has been shown that umbilical cord blood contains concentrations of
      hematopoietic progenitor cells equal to those of normal adult bone marrow. We
      successfully performed transplantation of cord blood combined with a
      hematopoietic growth factor (rGM-CSF) in a seven year old child suffering from
      neuroblastoma. Cord blood cells were collected from an HLA identical sibling at
      the time of delivery and stored in liquid nitrogen. The patient was conditioned
      with busulfan 600 mg/m2 and cyclophosphamide 200 mg/kg before receiving the
      thawed cells. There were no immediate side effects. Hematological reconstitution
      occurred promptly (granulocytes greater than 0.5 x 10(9)/L on day 13, platelets
      greater than 30 x 10(9)/L on day 40), although at day 10 the child experienced
      acute grade II cortico-sensitive GvHD. Mixed hematopoietic chimerism was observed
      2 months later and complete remission lasted for 8 months.

PMID- 1357626
TI  - Alpha 1- and beta-adrenergic interactions on L-type calcium current in cardiac
      myocytes.
AB  - We investigated the mechanism by which alpha 1-adrenergic activation regulates
      basal and stimulated whole cell L-type Ca current (ICa) in rat ventricular
      myocytes using the physiological neurotransmitter, norepinephrine (NE, 10
      microM). Stimulation of alpha 1-adrenoceptors, achieved by NE + 10 microM esmolol
      (a beta-receptor antagonist), had no significant effect on basal ICa. alpha 1
      adrenergic activation had a marked inhibitory effect on ICa elevated by beta
      activation (NE + 1 microM) prazosin, an alpha 1-receptor antagonist) or
      activation of adenylyl cyclase by forskolin (25 microM); the inhibitory effect
      was reversible upon washout. However, alpha 1-adrenergic stimulation had no
      significant effect on ICa previously increased by intracellular application of
      cAMP (25 microM). The inhibitory effect seen on ICa elevated by NE showed no
      significant shift of either I-V or inactivation curves. It is unlikely that the
      inhibitory effect of alpha 1-adrenergic stimulation on NE or forskolin-elevated
      ICa is mediated through activation of Ca-dependent protein kinase C or changes in
      intracellular free Ca (pCa = 8.5, EGTA 5 mM) or cAMP-dependent phosphodiesterase.
      We conclude that alpha 1-adrenergic inhibition of beta-adrenergic stimulated-ICa
      is probably mediated through an as yet unknown G-protein. This inhibitory effect
      could serve as a regulatory feedback mechanism in physiological and
      pathophysiological settings.

PMID- 1357629
TI  - Participation of glutamic acid 23 of T4 endonuclease V in the beta-elimination
      reaction of an abasic site in a synthetic duplex DNA.
AB  - T4 endonuclease V catalyzes the hydrolysis of the glycosyl bond of a thymine
      dimer in a DNA duplex and the cleavage of the 3'-phosphate by beta-elimination.
      We have previously identified a catalytic site for the first reaction (pyrimidine
      dimer-glycosylase activity) by systematic mutagenesis (Doi et al. Proc. Natl.
      Acad. Sci. USA 1992 in press) and by x-ray crystallography (Morikawa et al.
      Science, 256: 523-526, 1992). The results showed that replacement of Glu23 with
      either glutamine or aspartic acid completely abolished the glycosylase activity.
      We describe the investigation of the second reaction (apurinic/apyrimidinic
      endonuclease activity), using twenty two mutants of T4 endonuclease V plus a DNA
      mini duplex containing an abasic site. Replacement of Glu23 by glutamine
      abolished the second reaction, but replacement with aspartic acid did not. The pH
      optima of the mutant (23 Asp) and the wild type were found to be 5.0 and 5.5,
      respectively. We conclude that the carboxylate anion in position 23 may act as a
      general base in the beta-elimination reaction of the endonuclease.

PMID- 1357628
TI  - Differential DNA binding properties of three human homeodomain proteins.
AB  - The products of three human homeobox containing (HOX) genes, 2C, 3C and 4B, were
      produced in insect cells using the Baculovirus expression system and purified to
      near homogeneity. In this system we observed that the DNA binding forms of the
      three proteins are not glycosylated. HOX 3C and 4B are phosphorylated in insect
      cells, while HOX 2C is not. The three HOX proteins bind to a DNA sequence known
      to be a target site for Antennapedia protein with a very similar affinity (Kd = 1
      2 x 10(-9) M). We then measured their binding properties to four human sequences
      present in the HOX 3D, 4C, 1C and 4B promoters. Two of these sequences have been
      reported to be binding sites for HOX proteins. HOX 2C, 3C and 4B behaved quite
      differently, showing low affinity for promoters of genes located upstream from
      their own gene in the HOX clusters and a higher affinity for regulatory sequences
      of their own gene and downstream HOX genes.

PMID- 1357631
TI  - Pioneering assistants. Interview by Sandra Hempel.

PMID- 1357632
TI  - [Diagnosis and the methods of evaluating the degree of impairment of the immune
      system in HIV infection].

PMID- 1357630
TI  - A novel POU homeodomain gene specifically expressed in cells of the developing
      mammalian nervous system.
AB  - We report the isolation of a novel human POU domain encoding gene named RDC-1.
      The POU domain of the RDC-1 encoded protein is highly related to the POU domain
      potentially encoded by the rat brain-3 sequence and to that of the Drosophila I
      POU protein; outside of the POU region, RDC-1 is unrelated to any previously
      characterized protein. The RDC-1 gene is expressed almost exclusively in normal
      tissues and transformed cells of neural origin. In the developing mouse and human
      fetus, RDC-1 is expressed in a spatially and temporally restricted pattern that
      suggests a critical role in the differentiation of neuronal tissues. In addition,
      RDC-1 is expressed in a unique subset of tumors of the peripheral nervous system
      including neuroepitheliomas and Ewing's sarcomas but not neuroblastomas. Based on
      its unique structural characteristics and expression pattern, we discuss
      potential functions for the RDC-1 protein.

PMID- 1357634
TI  - Anatomical evidence for interactions between somatostatin neurites in lamina II
      of the rat spinal cord.
AB  - Light microscopic analysis of adult and 10-14-day-old rat spinal cords suggested
      that somatostatin-immunoreactive (SOM-I) fibers apposed SOM-I cell bodies in
      lamina (L) II. Electron microscopic analysis of these relationships at both ages
      showed the presence of direct appositions between SOM-I fibers and SOM-I cells.
      However, synapse formation between SOM-I fibers and cells was observed only in
      the young rat. Similarly, synapses between SOM-I fibers and SOM negative cell
      bodies were only found in the young animal. Adjacent SOM-I perikarya directly
      contacted each other, but, again, membrane specializations were evident only in
      the young rat. Within L I of the adult dorsal horn, a SOM-I fiber directly
      apposed an unlabeled cell body. Despite analysis of serial sections through the
      apposition, no synaptic contacts were observed.

PMID- 1357633
TI  - Regional distribution of pyroglutamyl peptidase II in rabbit brain, spinal cord,
      and organs.
AB  - Pyroglutamyl peptidase II (PPII) is a narrow specificity ectoenzyme that degrades
      thyrotropin-releasing hormone (TRH). We detected the enzyme in the brain of
      various mammals, with highest specific activity in rabbit brain. In this species,
      activity was heterogeneously distributed in the central nervous system. There was
      a 28-fold difference between regions of highest and lowest PPII activity. Enzyme
      activity was highest in the olfactory bulb and posterior cortex. In the spinal
      cord, activity was low but unevenly distributed, with highest values detected in
      the thoracic (T) region. Segments T1 and T2 activities were particularly high.
      Other organs contained low or undetectable levels of activity. The levels of TRH
      like immunoreactivity (TRH-LI) in spinal cord segments were greatest in T3-T4 and
      lumbar L2-L6. Low concentrations were found in T1 and T9-T12. There was a partial
      correlation between the distribution of PPII activity and TRH receptors but not
      with TRH-LI levels. These results demonstrate that PPII is predominantly a
      central nervous system enzyme, and they support the hypothesis that PPII is
      responsible for degrading TRH released into the synaptic cleft.

PMID- 1357635
TI  - Mentally abnormal offenders. Evaluation and management of violence.
AB  - Over the past two decades, much has been learned about the evaluation and
      management of violent patients. This has been translated into clinical guidelines
      for the evaluation and management of violent persons with psychiatric disorders.
      New research on neurotransmitters and the use of technology that can explore
      neurophysiologic and chemical activity in the brain promises continued advances
      in this area of psychiatry.

PMID- 1357636
TI  - D-Ala2,F5Phe4-dynorphin amide, an opiate with analgesic and toxic properties.
AB  - A novel analog of dynorphin (1-13), D-Ala2,F5Phe4-dynorphin amide, was prepared
      and its pharmacological spectrum of activity was investigated. In a hot plate
      test on Swiss Webster and C57Bl mice, a 20 micrograms intracerebroventricular
      (icv) dose of the analog produced analgesia, which was greater in potency and
      duration than the parent dynorphin. This action of D-Ala2,F5Phe4-dynorphin amide
      was antagonized by the opiate receptor antagonist naloxone (2 mg/kg ip),
      administered either before or after the peptide. In addition to its analgesic
      action in mice, D-Ala2,F5Phe4-dynorphin amide produced a Straub tail and a
      catatonic-like state, both of which were also attenuated by naloxone. On the
      electrically-stimulated mouse vas deferens preparation, in vitro, D-Ala2,F5Phe4
      dynorphin amide inhibited contractile activity and had an IC50 of 108.2 +/- 34.7
      nM (SEM), about 4-fold weaker than that of dynorphin. This action was also
      attenuated by naloxone. An icv dose of 150 micrograms of D-Ala2,F5Phe4-dynorphin
      amide in mice, and a cumulative series of icv doses up to 2600 micrograms in
      anesthetized rats, failed to produce a lethal effect. No pathological changes
      were observed in mouse liver and kidney at 24 h after a 50 mg/kg dose of the
      peptide analog. In rats anesthetized with diallylbarbital (70 mg/kg ip) and
      urethane (280 mg/kg ip), D-Ala2,F5Phe4-dynorphin amide did not modify blood
      pressure, heart rate and respiratory rate. However, when mice were injected
      peripherally with single doses of D-Ala2,F5Phe4-dynorphin amide, convulsive
      episodes were produced, and lethal effects were observed with an LD50 of 60.0
      mg/kg (95% confidence limits: 49.7-70.2 mg/kg) at 48 h. This action of D
      Ala2,F5Phe4-dynorphin amide was not attenuated by naloxone (2.0 mg/kg, ip).
      Although analgesic and behavioral effects of D-Ala2,F5Phe4-dynorphin amide (e.g.
      Straub tail and catatonic-like state) are opiate-like, the lethal effect may be
      the consequence of actions of the peptide on non-opiate systems, Thus, the novel
      fluorinated dynorphin analog, D-Ala2,F5Phe4-dynorphin amide, may be a useful
      chemical tool for the study of opiate systems and their occasionally
      unanticipated biological or toxic actions.

PMID- 1357637
TI  - Involvement of dopamine autoreceptors in the hypoactivity induced by 8-hydroxy-2
      (di-n-propylamino)tetralin (8-OH-DPAT) in mice.
AB  - The effect of 8-OH-DPAT, a 5-HT1A receptor agonist, on the locomotor activity was
      analyzed in Albino Swiss mice. The studied drug (0.5-5 mg/kg) inhibited the
      spontaneous locomotor activity in mice. The hypoactivity induced by 8-OH-DPAT
      (1.5 mg/kg) was abolished by the dopamine (D1 and D2) receptor antagonist
      haloperidol (0.00125 and 0.0025 mg/kg, but not in higher doses) and by the D2
      antagonist with affinity for 5-HT1A and 5-HT2 receptors-spiperone (0.0025 and
      0.005 mg/kg, but not in higher doses). The effect of 8-OH-DPAT was slightly
      reduced by the alpha 2-adrenoceptor antagonists: idazoxan (4 mg/kg), yohimbine (2
      and 4 mg/kg) and rauwolscine (4 mg/kg). On the other hand, the non-selective 5-HT
      antagonist metergoline (0.5-4 mg/kg), the 5-HT1A antagonist NAN-190 (0.5-2
      mg/kg), the beta-adrenoceptor blockers with high affinity for 5-HT1A and 5-HT1B
      receptors: pindolol and SDZ 21009 (2-8 mg/kg) and the agonist/antagonist of 5
      HT1A receptors ipsapirone (2.5 and 5 mg/kg) did not affect the 8-OH-DPAT-induced
      hypoactivity. The obtained results suggest that the reduction of the spontaneous
      locomotor activity induced by 8-OH-DPAT results from a stimulation of dopamine
      autoreceptors, but not 5-HT receptors. Involvement of an alpha 2-adrenergic
      mechanism cannot be excluded.

PMID- 1357638
TI  - Tourette's syndrome. Current approaches to recognition and management.
AB  - Once thought to be a rare, disabling disorder of psychogenic origin, Tourette's
      syndrome is now recognized as a chronic neurologic condition that is manageable
      in most patients. Individualized therapy is the key to helping patients achieve a
      productive and socially integrated life-style. This article discusses diagnostic
      criteria, effective management strategies, and promising new drug therapies.

PMID- 1357640
TI  - Recent advances in cardiomyopathy and cardiovascular pharmacotherapy. Proceedings
      of an International Congress. Macedonia, Greece, May 29-June 2, 1990.

PMID- 1357641
TI  - The treatment of stable angina pectoris.
AB  - A review of the available therapeutic measures for the management of stable
      angina pectoris is presented. The subject is critically examined by focusing on 5
      main categories: general measures, drug therapy, coronary artery by-pass surgery,
      percutaneous transluminal coronary angioplasty and the handling of associated
      illnesses or disorders. General measures provide attention to the control or
      removal of aggravating conditions and to the institution of alterations in habits
      and life-style that will benefit the patient. Drug therapy depends upon the use
      of nitrates, beta adrenergic blockers and calcium entry blockers either alone or
      in combination. The mechanism of action of different drugs, its indications, as
      well as the dosage and frequency of use are reviewed. The indications for
      coronary artery by-pass surgery are presented as well as those for percutaneous
      transluminal angioplasty. An orientation in the selection of specific drugs when
      important concomitant diseases, such as hypertension and diabetes, coexist with
      stable angina pectoris is offered. The rationale behind the different
      alternatives is presented.

PMID- 1357639
TI  - Molecular biology of neurological diseases.

PMID- 1357643
TI  - Proceedings of the VIIth Congress of the Italian Association of
      Immunopharmacology. Stresa, November 14-16, 1991.

PMID- 1357642
TI  - Inhibition of nicotine-induced relaxation of the bovine retractor penis muscle by
      beta-adrenoceptor antagonists.
AB  - The relative potency in inhibiting nicotine-induced relaxation of the bovine
      retractor penis muscle (BRP) was estimated for the racemates of seven beta
      adrenoceptor antagonists, both of the optical isomers of propranolol, and
      lidocaine. The order of potency of the drugs studied was (+)-propranolol greater
      than (-)-propranolol greater than propranolol greater than alprenolol greater
      than metoprolol greater than lidocaine greater than acebutolol greater than
      pindolol greater than sotalol greater than atenolol. It is concluded that the
      inhibition of the relaxation was not due to blockade of beta-adrenoceptors but to
      the nonspecific effects of the beta-adrenoceptor antagonists. It is also
      concluded that the neurotransmitter(s) which was (were) released from the non
      adrenergic non-cholinergic inhibitory nerves in the BRP did not relax the muscle
      by activating the beta-adrenoceptors. It is suggested that the beta-adrenoceptor
      antagonists inhibited the release of the inhibitory neurotransmitter(s) by a
      mechanism which is significantly correlated to their lipophilicity.

PMID- 1357644
TI  - Number and functionality of beta-adrenergic receptors in the mouse lymphocytic
      P388 leukemia as a doxorubicin-sensitive and -resistant variant.

PMID- 1357647
TI  - Natural reactivities against normal and neoplastic hemopoietic cell grafts by
      lethally irradiated mice.

PMID- 1357646
TI  - Stress and the immune system.

PMID- 1357645
TI  - Inhibitory mechanisms and modulation of anaphylactic reaction in guinea-pig
      airways.

PMID- 1357649
TI  - Proceedings from the XIVth International Pigment Cell Conference. Kobe, Japan,
      October 31-November 4, 1990.

PMID- 1357648
TI  - Principles and criteria in the development and optimization of topical
      therapeutic products.

PMID- 1357651
TI  - [Isolated coronary arteritis--case report and discussion of nomenclature].

PMID- 1357652
TI  - [Signals regulating arterial vasomotricity and vasotrophicity].
AB  - Second messengers regulating the level of free intracellular calcium and the
      level of phosphorylation (kinase activities) transduce within the cells the
      mechanical and biochemical (endocrine, paracrine and autocrine) signals detected
      by the arterial wall. In arterial smooth muscle cells two signalling pathways
      produce opposite functional and structural effects: the breakdown of
      phosphoinositol leading to an increase in intracellular calcium level, and the
      cyclic guanosine monophosphate (GMP) pathway resulting in a decrease in calcium
      level. The arterial cyclic GMP pathway is predominantly under control of the
      endothelial function to secrete no rather than influenced by the atrial
      natriuretic factor. These two intracellular second messenger pathways are
      involved not only in the regulation of motricity, but also in the control of
      arterial wall trophicity, including hypertrophy, hyperplasia and collagen
      hypersecretion. Inactivation of the cyclic GMP pathway and activation of
      phosphoinositol breakdown predominate in vascular adaptation to the ageing
      process.

PMID- 1357650
TI  - Modulation of the antigenic phenotype of human melanoma cells by differentiation
      inducing and growth-suppressing agents.
AB  - Tumor cells often display alterations in their normal program of cellular
      differentiation. A promising approach for the treatment of cancer involves the
      induction of terminal differentiation and a loss of proliferative capacity in
      cancer cells. In human melanoma cells, the combination of mezerein (MEZ) and
      fibroblast interferon (IFN-beta), results in a rapid and irreversible suppression
      of cell growth with a concomitant increase in the synthesis of melanin. The
      induction of terminal differentiation is associated with alterations in the
      expression of several cellular genes, including fibronectin, ISG-15 and ISG-54,
      and changes in the expression of specific cell surface antigens, including
      intercellular adhesion molecule-1 (ICAM-1) and HLA Class I antigens. In the HO-1
      human melanoma cell line, induction of terminal differentiation by MEZ plus IFN
      beta results in an induction and/or increased expression of ICAM-1, HLA Class I
      antigens and HLA Class II antigens. IFN-beta and MEZ alone can modulate
      expression of these antigens to a lower extent than does the combination of
      compounds. Induction of terminal differentiation and the irreversible suppression
      of cell growth is not a prerequisite for antigenic modulation in HO-1 cells. This
      is indicated by the inability of immune interferon (IFN-gamma), a strong inducer
      of ICAM-1, HLA Class I antigens and HLA Class II antigens synthesis, or the
      combination of IFN-beta plus IFN-gamma which synergistically but reversibly
      suppresses HO-1 growth, to induce melanin synthesis or terminal differentiation
      in HO-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357653
TI  - [Risk-benefit assessment and value of beta-2-sympathomimetic drugs in asthma
      therapy].

PMID- 1357654
TI  - [Symposium on the "hyperventilation syndrome"].

PMID- 1357655
TI  - Comparison of Giardia isolates from different laboratories by isoenzyme analysis
      and recombinant DNA probes.
AB  - A total of 13 new Giardia isolates were established in axenic culture. All of the
      new isolates were obtained by excystation of Giardia cysts from the feces of
      patients in Dutch hospitals. These isolates were subjected to isoenzyme and DNA
      analysis together with isolates from Poland, Belgium, and various other parts of
      the world. Isoenzyme analysis revealed that nearly all of the newly established
      isolates exhibited unique zymodemes. Isolates obtained from individuals from
      Belgium and Poland, on the other hand, displayed single zymodemes. Genomic DNA
      libraries were constructed from isolates belonging to the latter two zymodemes;
      specific and common recombinant DNA clones were selected from these libraries.
      Differential screening revealed that the two isolates had only 80% of the clones
      in common. Restriction-fragment-length polymorphism analysis using three
      different probes together with two synthetic probes that are complementary to
      Giardia structural protein genes led to the separation of all isolates into two
      major groups; within these groups, a further division could be made by
      application of other techniques or probes. The results of DNA analysis and
      zymodeme classification were in general agreement; in the present report they are
      compared with the data in the literature and discussed.

PMID- 1357656
TI  - Overproduction, preparation of monoclonal antibodies and purification of E. coli
      asparagine synthetase A.
AB  - In order to explore the structure--function relationship of the Escherichia coli
      asparagine synthetase A it was necessary to devise a system for overexpression of
      the gene and purification of the gene product. The E. coli asparagine synthetase
      A structural gene was fused to the 3' end of the human carbonic anhydrase II
      structural gene and overexpressed in E. coli. The gene product, a 66 kDa fusion
      protein, which exhibited asparagine synthetase activity, was purified in a single
      step by affinity chromatography and used as the antigen for the production of
      monoclonal antibodies. The monoclonal antibodies were screened by ELISA. Colonies
      were chosen which were positive for purified fusion protein and negative for
      purified human carbonic anhydrase II. The E. coli asparagine synthetase A gene
      was then overexpressed and the gene product was used without purification for the
      final screen. The antibodies selected were used for immunoaffinity chromatography
      to purify the recombinant overexpressed E. coli asparagine synthetase A. Thus, a
      procedure is now available so that asparagine synthetase A can be purified to
      homogeneity in a single step.

PMID- 1357657
TI  - Alkaline phosphatase-somatostatin hybrid proteins as probes for somatostatin-14
      receptors.
AB  - By inserting appropriate peptide ligands into surface loops on globular proteins,
      we expect to develop probes for the location, accessibility, and steric and
      electrostatic environment of these ligand-binding sites on their membrane-bound
      receptors. Three residues in a loop on the surface of E. coli alkaline
      phosphatase were substituted by an 18-residue peptide containing the receptor
      binding segment of somatostatin-14 without significantly affecting the catalytic
      properties of the enzyme. This hybrid protein was then used to investigate the
      ligand-binding site of somatostatin receptors. Tryptic cleavage of the hybrid
      protein within the inserted sequence, and binding of the hybrid protein to
      antisomatostatin antibodies demonstrated the surface accessibility of the guest
      peptide. Both the wild-type enzyme and the hormone-enzyme hybrid displaced 125I
      labeled somatostatin from rat brain membrane receptors only at high
      concentrations. However, chemical cationization of the hybrid protein, which
      again did not disturb the phosphatase activity, enhanced its receptor-binding
      potency to a level only 23 times lower than that of somatostatin itself and 280
      times higher than that of the cationized wild-type protein. This alkaline
      phosphatase/somatostatin hybrid protein appears, therefore, to be a suitable
      starting point for the development of probes for the steric and electrostatic
      environment of the ligand-binding site of somatostatin receptors.

PMID- 1357658
TI  - Specific modulation of dopamine expression in neuronal hybrid cells by primary
      cells from different brain regions.
AB  - MN9D is an immortalized dopamine-containing neuronal hybrid cell line. When MN9D
      cells were coaggregated with primary embryonic cells of optic tectum, a brain
      region that does not receive a dopaminergic innervation, there was a marked
      reduction in their dopamine content, tyrosine hydroxylase immunoreactivity, and
      tyrosine hydroxylase mRNA. Similar reductions in dopamine content were produced
      by coaggregation with cells from embryonic thalamus, another brain region devoid
      of dopaminergic innervation. Coaggregation of MN9D cells with dopaminoceptive
      cells from the corpus striatum or the cortex did not have a demonstrable
      stimulatory effect on the dopamine content of MN9D cells. The decrease in MN9D
      dopamine content produced by optic tectum cells was not reversed by addition of
      corpus striatum cells. Thus, the MN9D hybrid cells are able to respond to an
      inhibitory factor(s) from cells derived from brain areas that are not targets for
      dopaminergic neurons. Catecholamine-producing PC12 cells did not respond in a
      similar manner, suggesting that the response of MN9D cells is a function of their
      mesencephalic origin. Given the selective response of MN9D cells to different
      brain cell populations, this hybrid cell line should facilitate investigations of
      cell-cell interactions in the central nervous system that may be involved in the
      expression of neurotransmitter phenotype and establishment of specific neuronal
      connections.

PMID- 1357659
TI  - Differential expression of arachidonate 5-lipoxygenase transcripts in human brain
      tumors: evidence for the expression of a multitranscript family.
AB  - In addition to the important role of leukotrienes as mediators in allergy and
      inflammation, these compounds are also linked to pathophysiological events in the
      brain including cerebral ischemia, brain edema, and increased permeability of the
      blood-brain barrier in brain tumors. Although brain tumors have been shown to
      secrete leukotrienes, no studies to date have provided evidence for the tumor
      expression of genes encoding enzymes involved in leukotriene production.
      Therefore, the present study determined the abundance of the mRNA for
      arachidonate 5-lipoxygenase (5-LO; arachidonate:oxygen 5-oxidoreductase, EC
      1.13.11.34), which is the rate-limiting enzyme in leukotriene synthesis, in a
      series of human brain tumors. Macrophage/monocyte infiltration of the tumor was
      estimated by measuring the abundance of the transcript for the 91-kDa
      glycoprotein phagocyte-specific oxidase (gp91-phox), which is the phagocyte
      specific cytochrome b heavy chain. The present study shows that (i) the 5-LO
      transcript is expressed in normal bovine brain and in human brain tumors; (ii)
      the 5-LO gene in human brain tumors and in the dimethyl sulfoxide-induced
      promyelocytic human leukemic HL-60 cells is expressed as a multitranscript family
      (2.7, 3.1, 4.8, 6.4, 8.6 kilobases); and (iii) the abundance of 5-LO transcripts,
      the expression of the larger transcripts, and the 5-LO/gp91-phox ratio correlate
      with the tumor malignancy. Overall, the present study supports the hypothesis
      that the 5-LO gene product may play a role in human tumor-induced brain edemas
      and provides evidence for tumor-associated expression of high molecular weight 5
      LO transcripts in human brain tumors.

PMID- 1357660
TI  - Leukotriene A4 hydrolase: abrogation of the peptidase activity by mutation of
      glutamic acid-296.
AB  - The metal-binding motif in the sequence of leukotriene A4 (LTA4) (EC 3.3.2.6), a
      bifunctional zinc metalloenzyme, contains a glutamic acid that is conserved in
      several zinc hydrolases. To study its role for the two catalytic activities, Glu
      296 in mouse leukotriene A4 hydrolase was replaced by a glutamine or alanine
      residue by site-directed mutagenesis. Wild-type and mutated cDNAs were expressed
      four or five times in Escherichia coli, and the resulting proteins were purified
      to apparent homogeneity. With respect to their epoxide hydrolase activities-
      i.e., the conversion of LTA4 into leukotriene B4--the mutated enzymes
      [Gln296]LTA4 hydrolase and [Ala296]LTA4 hydrolase exhibited specific activities
      of 1070 +/- 160 and 90 +/- 30 nmol of LTB4 per mg of protein per min (mean +/-
      SD; n = 4 or 5), respectively, corresponding to 150% and 15% of unmutated enzyme.
      In contrast, when the mutated proteins were assayed for peptidase activity toward
      alanine-4-nitroanilide, they were found to be virtually inactive (less than or
      equal to 0.2% of unmutated enzyme). To serve as a positive control, we also
      replaced Ser-298 with an alanine residue, which resulted in a protein
      ([Ala298]LTA4 hydrolase) with catalytic properties almost indistinguishable from
      the wild-type enzyme. Substitution of Glu-296 by glutamine or alanine was also
      carried out with human LTA4 hydrolase, and the mutated human enzymes displayed
      specific activities similar to the corresponding mouse proteins. Zinc analyses of
      the purified mouse and human proteins confirmed that the mutations did not
      significantly influence their zinc content. In conclusion, the results of the
      present study indicate a direct catalytic role for Glu-296 in the peptidase
      reaction of LTA4 hydrolase, where it presumably acts as a base to polarize water,
      whereas its function, if any, is apparently not essential in the epoxide
      hydrolase reaction.

PMID- 1357661
TI  - Activation of a D2 receptor increases electrical coupling between retinal
      horizontal cells by inhibiting dopamine release.
AB  - In the fish retina, interplexiform cells release dopamine onto cone-driven
      horizontal cells. Dopamine decreases the electrical coupling between horizontal
      cells by activating adenylate cyclase through dopamine D1 receptors. Using
      intracellular recording, we have studied the effect of dopamine D2 receptor
      activation on horizontal cell electrical coupling in the intact goldfish retina.
      Superfusion of the D2 agonist LY171555 (quinpirole; 0.2-10 microM) increased
      horizontal cell coupling, as indicated by a decrease in responses to centered
      spots or slits of light. The length constant of the horizontal cell network
      increased an average of 31%. Although dopamine (0.5-20 microM) uncoupled
      horizontal cells, lower concentrations (e.g., 0.2 microM) initially uncoupled and
      then subsequently increased coupling beyond initial control levels. The coupling
      effect of LY171555 (10 microM) was blocked completely by prior application of the
      D1 agonist SKF 38393 at saturating (20 microM) or nonsaturating (2.5-5.0 microM)
      doses. Prior treatment of the retinas with 6-hydroxydopamine, which destroyed
      dopaminergic neurons, eliminated the coupling effect of LY171555 but not the
      uncoupling effect of SKF 38393. These results suggest that goldfish horizontal
      cells contain D1, but not D2, receptors and that dopamine activation of D2
      autoreceptors on interplexiform cells inhibits dopamine release onto horizontal
      cells so that the electrical coupling between horizontal cells increases.

PMID- 1357662
TI  - Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II.
AB  - Tyrosinemia type II (Richner-Hanhart syndrome, RHS) is a disease of autosomal
      recessive inheritance characterized by keratitis, palmoplantar hyperkeratosis,
      mental retardation, and elevated blood tyrosine levels. The disease results from
      deficiency in hepatic tyrosine aminotransferase (TAT; L-tyrosine:2-oxoglutarate
      aminotransferase, EC 2.6.1.5), a 454-amino acid protein encoded by a gene with 12
      exons. To identify the causative mutations in five TAT alleles cloned from three
      RHS patients, chimeric genes constructed from normal and mutant TAT alleles were
      tested in directing TAT activity in a transient expression assay. DNA sequence
      analysis of the regions identified as nonfunctional revealed six different point
      mutations. Three RHS alleles have nonsense mutations at codons 57, 223, and 417,
      respectively. One "complex" RHS allele carries a GT----GG splice donor mutation
      in intron 8 together with a Gly----Val substitution at amino acid 362. A new
      splice acceptor site in intron 2 of the fifth RHS allele leads to a shift in
      reading frame.

PMID- 1357663
TI  - Prion protein preamyloid and amyloid deposits in Gerstmann-Straussler-Scheinker
      disease, Indiana kindred.
AB  - Gerstmann-Straussler-Scheinker disease (GSS) is a familial neurological disorder
      pathologically characterized by amyloid deposition in the cerebrum and
      cerebellum. In GSS, the amyloid is immunoreactive to antisera raised against the
      prion protein (PrP) 27-30, a proteinase K-resistant peptide of 27-30 kDa that is
      derived by limited proteolysis from an abnormal isoform of a neuronal
      sialoglycoprotein of 33-35 kDa designated PrPSc. Polyclonal antibodies raised
      against synthetic peptides homologous to residues 15-40 (P2), 90-102 (P1), and
      220-232 (P3) of the amino acid sequence deduced from hamster PrP cDNA were used
      to investigate immunohistochemically the distribution of PrP and PrP fragments in
      the brains of two patients from the Indiana kindred of GSS. Two types of anti-PrP
      immunoreactive deposits were found: (i) amyloid deposits, which were exclusively
      labeled by anti-P1 antiserum to residues 90-102 of PrP, and (ii) preamyloid
      deposits, which were labeled by all anti-PrP antisera but did not exhibit the
      tinctorial and optical properties of amyloid. The latter appeared as diffuse
      immunostaining of the neuropil that targeted to areas in which amyloid deposits
      were most abundant. They were partially resistant to proteinase K digestion and
      consisted ultrastructurally of amorphous, flaky, electron-dense material. These
      findings substantiate our previous observation that the major amyloid component
      in the GSS Indiana kindred is an internal fragment of PrP and indicate that full
      length abnormal isoforms of PrP and/or large PrP fragments accumulate in brain
      regions most affected by amyloid deposition. These findings support the view that
      in the GSS Indiana kindred a stepwise degradation of PrP occurs in situ in the
      process of amyloid fibril formation.

PMID- 1357664
TI  - Instability of assembled T-cell receptor complex that is associated with rapid
      degradation of zeta chains in immature CD4+CD8+ thymocytes.
AB  - The intracellular fate of newly synthesized T-cell receptor (TCR) chains was
      compared in CD4+CD8+ (double positive; DP) thymocytes and in CD4+CD8- or CD4-CD8+
      (single positive; SP) thymocytes. Purified DP and SP thymocytes from normal adult
      mice were analyzed by pulse-chase metabolic labeling and immunoprecipitation with
      specific anti-TCR antibodies. Biosynthesis of invariant chains (CD3 gamma, 
      delta, -epsilon, and zeta) was comparable between DP and SP thymocytes, whereas
      DP thymocytes synthesized TCR alpha and TCR beta chains at lower and higher
      levels than SP thymocytes, respectively. These newly synthesized TCR chains were
      degraded at different rates in SP thymocytes based on their sensitivities for
      degradation as previously reported: TCR alpha, TCR beta, CD3 gamma, and CD3 delta
      chains were rapidly degraded and CD3 epsilon and zeta chains were stable.
      Although the degradation rates of clonotypic and invariant CD3 chains were
      similar in DP and SP thymocytes, the zeta subunit was rapidly degraded in DP
      thymocytes (t1/2, approximately 1.5 hr). Degradation of zeta was inhibited by
      NH4Cl, implicating lysosomes as the site of degradation. Comparison of TCR
      subunit assembly in DP and SP thymocytes demonstrated that, despite the same
      relative rate of formation of TCR complexes in a pulse period (30 min), complete
      complexes were unstable and degraded during the subsequent 6 hr of chase in DP
      thymocytes. This contrasted with the stability and a progressive increase in the
      levels of completely assembled complexes in SP thymocytes. Thus, these results
      demonstrate that a unique posttranslational regulation operates in the formation
      of TCR complexes in DP thymocytes and that lack of stability of complete TCR
      complexes is a crucial mechanism that may account for the limited surface TCR
      expression on this thymocyte subset.

PMID- 1357665
TI  - Regulation of recombinant rat tyrosine hydroxylase by dopamine.
AB  - Recombinant rat PC12 tyrosine hydroxylase, also called tyrosine 3-monooxygenase
      [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC
      1.14.16.2], purified from Escherichia coli is in an activated form with a low Km
      for the tetrahydrobiopterin cofactor and a pH optimum of 6.5. Pretreatment with
      low levels of the derived product, dopamine, inhibits catalytic activity,
      increases the Km for the cofactor, and shifts the pH curve towards a more acidic
      pH optimum. Labeled dopamine binds to tyrosine hydroxylase with high affinity (Kd
      = 1 microM) but low stoichiometry (r = 0.08 mol/mol of enzyme subunit). The
      binding of dopamine results in the appearance of a blue-green chromophore with
      lambda max at approximately 660 nm, which is consistent with the formation of a
      catecholamine-iron complex. In the absence of dopamine, the recombinant enzyme
      cannot be further activated by phosphorylation with cAMP-dependent protein
      kinase, although as much as 1 mol of phosphate is incorporated per mol of
      subunit. In contrast, the enzyme pretreated with dopamine is activated by
      phosphorylation in the same fashion and to the same extent as the native
      hydroxylase. The results suggest that the high-affinity binding of catecholamine
      products is a pivotal post-translational modification that determines the state
      of enzyme activation and the response to phosphorylation.

PMID- 1357666
TI  - Somatostatin receptors are expressed by immature cerebellar granule cells:
      evidence for a direct inhibitory effect of somatostatin on neuroblast activity.
AB  - Somatostatin and somatostatin receptors are transiently expressed in the immature
      rat cerebellar cortex but virtually undetectable in the cerebellum of adults.
      Although somatostatin binding sites have been visualized during the postnatal
      period in the external granule cell layer, the type of cell that expresses
      somatostatin receptors has never been identified; thus, the potential function of
      somatostatin in the developing cerebellum remains unknown. In the present study,
      we have taken advantage of the possibility of obtaining a culture preparation
      that is greatly enriched in immature cerebellar granule cells to investigate the
      presence of somatostatin receptors and the effect of somatostatin on
      intracellular messengers on cerebellar neuroblasts in primary culture.
      Autoradiographic labeling revealed the occurrence of a high density of binding
      sites for radioiodinated Tyr-[D-Trp8]somatostatin-(1-14) on 1-day-old cultured
      immature granule cells. Saturation and competition studies showed the existence
      of a single class of high-affinity binding sites (Kd = 0.133 +/- 0.013 nM, Bmax =
      3038 +/- 217 sites per cell). Somatostatin induced a dose-dependent inhibition of
      forskolin-evoked cAMP formation (ED50 = 10 nM), and this effect was prevented by
      preincubation of cultured immature granule cells with pertussis toxin.
      Somatostatin also caused a marked reduction of intracellular calcium
      concentration. These results show the presence of functionally active
      somatostatin receptors on immature granule cells. Our data suggest the possible
      involvement of somatostatin in the regulation of proliferation and/or migration
      of neuroblasts during the development of the cerebellar cortex.

PMID- 1357667
TI  - Transfer and expression of the human multiple drug resistance gene into live
      mice.
AB  - The human multiple drug resistance (MDR) gene has been used as a selectable
      marker to increase the proportion of bone marrow cells that contain and express
      this gene by drug selection. By constructing retroviral vectors containing and
      expressing the MDR gene and a nonselectable gene such as the beta-globin gene,
      enrichment for cells containing both of these genes can be achieved. A retroviral
      construct containing MDR cDNA in a Harvey virus-based vector has been used to
      transfect our ecotropic 3T3 retroviral packaging line GP+E86. Clones have been
      isolated by exposure of the retrovirally transfected cells (MDR producer cells)
      to colchicine (60 ng/ml), a selective agent that kills MDR-negative cells. Flow
      cytometry analysis (fluorescence-activated cell sorting) with an antibody to MDR
      demonstrates expression of human MDR protein on the surface of these colchicine
      resistant producer clones. Untransfected GP+E86 cells are negative. Colchicine
      resistant clones were titered using clone supernatants and the highest titer
      clone (4 x 10(4) viral particles per ml) was cocultured with 10(6) donor mouse
      bone marrow cells for 24-48 hr. The donor cells were then injected into congenic
      irradiated mice, and the presence of the MDR gene was assayed by the polymerase
      chain reaction (PCR) analysis using MDR-specific primers. In one experiment eight
      of nine transduced mice were positive for MDR by PCR of peripheral blood 14 and
      50 days posttransplantation; after 240 days three of nine transduced mice were
      positive. Bone marrow obtained from one of these positive animals was stained
      with the MDR monoclonal antibody and the granulocyte population was analyzed by
      FACS. Approximately 14% of the total granulocyte pool contain increased levels of
      MDR protein. In addition, the bone marrow cells of several mice initially
      positive for MDR gene by PCR, and subsequently negative, were exposed to taxol, a
      drug whose detoxification depends on MDR gene expression; a positive signal was
      obtained in all of these mice, indicating drug selection of MDR-positive marrow
      cells. Cell sorting studies of these mice also show an increased number of high
      MDR-expressing marrow cells, selected after exposure to taxol. Thus, in this live
      animal model MDR transduction is effective in selecting a human MDR-expressing
      population of marrow cells resistant to taxol chemotherapy. This strategy may,
      thus, be useful in humans to prevent the marrow toxicity induced by anticancer
      agents such as taxol and as a selectable marker to enrich for cells
      simultaneously transduced with a nonselectable gene.

PMID- 1357668
TI  - Homology of a vesicular amine transporter to a gene conferring resistance to 1
      methyl-4-phenylpyridinium.
AB  - The vesicular amine transporter (VAT) catalyzes transport and storage of catechol
      and indolamines into subcellular organelles in a wide variety of cells. It plays
      a central role in neurotransmission and is the primary target for several
      pharmacological agents. One of the drugs, reserpine, binds very tightly to the
      transporter and remains bound even after solubilization, a finding that has
      proven useful for purification of the transporter from bovine adrenal medulla in
      a fully functional state. The sequences of 26 N-terminal amino acids and of an
      additional 7-amino acid internal peptide are presented. Antibodies against a
      synthetic peptide based on the above sequences immunoprecipitate the transporter,
      confirming the conclusion that the peptide sequence is derived from bovine VAT.
      To our knowledge, documentation of sequences of vesicular neurotransmitter
      transporters has not been presented previously. In addition, the sequences
      obtained are highly homologous to the predicted sequence of a protein from PC12
      cells that confers to Chinese hamster ovary cells resistance to 1-methyl-4
      phenylpyridinium (MPP+), an agent that causes parkinsonism in model systems,
      confirming the hypothesis that the protein conferring resistance to MPP+ is a
      VAT.

PMID- 1357671
TI  - Down syndrome and alzheimer disease. Proceedings of the National Down Syndrome
      Society Conference on Down Syndrome and Alzheimer Disease. New York, January 16
      17, 1992.

PMID- 1357669
TI  - Cloning and expression of chicken erythrocyte transglutaminase.
AB  - We report the sequences of cDNAs encoding chicken erythrocyte transglutaminase
      (EC 2.3.2.13). The complete mRNA consists of 3345/3349 nucleotides and predicts a
      single open reading frame. Nine peptide sequences derived from partial digests of
      the isolated protein agreed with the corresponding translation of the open
      reading frame. Approximately 60% identities between the avian protein and three
      related mammalian enzymes were found. Chicken erythrocyte transglutaminase mRNA
      is most abundant in red blood cells and kidney, and it accumulates during
      erythroid cell differentiation.

PMID- 1357672
TI  - Effects of methamphetamine and ethanol on learning and brain neurotransmitters in
      rats.
AB  - The interactions of methamphetamine (MAMP) and ethanol (EtOH) on multiple
      active/passive avoidance performance and neurotransmitters in different brain
      regions were examined. After the acquisition schedules, rats were retrained under
      the influence of MAMP (2 mg/kg/day, IP), EtOH (2 g/kg/day, IP), and in
      combination over 20 days in rats (n = 6 per group). As a function of progress of
      drug treatment, MAMP-EtOH mixtures disrupt the learned avoidance performance and
      produced severe impairment of discriminative behavior caused by enhancement of
      excitability induced by MAMP when compared with MAMP only. At withdrawal, MAMP
      EtOH-induced impairments of performance significantly persisted, whereas MAMP
      only-induced impairments slightly recovered. At the eleventh day drug withdrawal,
      MAMP-only-induced alterations of neurotransmitter levels at different regions
      were alleviated by EtOH, but these did not return to normal levels. These data
      provide support for the direct antagonistic and indirect additive interactions
      following constant daily treatment with a combination of MAMP and EtOH. EtOH may
      be an important factor in MAMP abuse to MAMP-induced psychosis or neurotoxicity.

PMID- 1357670
TI  - Cloning, genetic mapping, and expression analysis of an Arabidopsis thaliana gene
      that encodes 1-aminocyclopropane-1-carboxylate synthase.
AB  - A genomic clone of one member of the Arabidopsis thaliana (L.) Heynh. 1
      aminocyclopropane-1-carboxylate (ACC) synthase (S-adenosyl-L-methionine
      methylthioadenosine-lyase, EC 4.4.1.14) gene family (AT-ACC1) was isolated and
      sequenced. A region of homology was found in the 5'-untranslated region with the
      promoter of a zucchini and a tomato ACC synthase gene. Comparison of its primary
      structure with other ACC synthases revealed conservation of seven peptide regions
      as well as similarity with 11 amino acids of the catalytic site of
      aminotransferases. Genomic DNA gel blotting suggested the existence of an ACC
      synthase multigene family in Arabidopsis, possibly with three other members, none
      of which is very closely related to AT-ACC1. The existence of at least one other
      gene was confirmed by the isolation of a cDNA (AT-ACC2) from a flower-specific
      cDNA library. The AT-ACC1 gene was mapped on the Arabidopsis restriction fragment
      length polymorphism map and is located on the top of chromosome 1. This position
      does not correspond to any known mutation on the genetic map. Expression of the
      AT-ACC1 gene was studied by reverse transcription-PCR on total RNA. Messenger
      accumulation was strong in young leaves and flowers. The gene was not induced by
      wounding of young leaves or in seedlings in the presence of auxin. Ethylene
      exposure of mature plants led to an induction of AT-ACC1 gene expression. It is
      suggested that AT-ACC1 protein has a role in developmental control of ethylene
      synthesis.

PMID- 1357673
TI  - Beta-blocker effects on 24-h activity in normotensive and renovascular
      hypertensive baboons.
AB  - Spontaneous motor activity of normotensive and renovascular hypertensive baboons
      was measured during oral dosing with the beta-adrenergic antagonists atenolol HCl
      (2.6 mg/kg/day) and d,l-propranolol HCl (6.8 mg/kg twice daily) in separate
      studies. Each study administered active drug for 21 consecutive days.
      Piezoelectric monitors sensitive to movement were worn continuously by the
      baboons. Propranolol decreased overall 24-h average activity during the third
      week of dosing in normotensive baboons but not in renovascular hypertensive
      baboons. The greatest reductions in activity averaged 20% at those times of day
      corresponding to the second daily drug dose both in normotensive baboons and, at
      this time of day only, in the majority of hypertensive baboons. Activity
      decreases reversed to baseline levels when propranolol was discontinued. For
      atenolol, most normotensive but no hypertensive baboons showed decreases in
      activity at the time of day corresponding to the daily drug dose.

PMID- 1357674
TI  - Assessment of the stimulus properties of anxiolytic drugs by means of the
      conditioned taste aversion procedure.
AB  - The conditioned taste aversion (CTA) procedure has recently been described as a
      more rapid alternative to two-lever operant procedures in drug discrimination
      research. We trained different groups of rats to discriminate the benzodiazepine
      chlordiazepoxide (CDP, 20 mg/kg) or the 5-hydroxytryptamine1A (5-HT1A) agonist 8
      hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.4 mg/kg) from saline by means
      of the CTA procedure. The results were in agreement with findings from two-lever
      operant drug discrimination procedures. However, discrimination training took 40
      sessions in the case of CDP and 72 sessions for 8-OH-DPAT, which is comparable to
      results obtained with two-lever operant procedures. Dose-response curves were
      determined and generalization tests were performed for different benzodiazepine
      and nonbenzodiazepine anxiolytics. Baseline behavior deteriorated in the course
      of generalization and substitution testing, thus preventing further
      generalization testing. Our experience is that the use of the CTA procedure in
      drug discrimination research does not have sufficient advantages over
      traditionally used procedures to replace the latter.

PMID- 1357675
TI  - Attenuation of alcohol consumption by MDMA (ecstasy) in two strains of alcohol
      preferring rats.
AB  - Alcohol preference and manifestation of alcoholism are thought by many to be
      associated with serotonin (5-HT) dysfunction in the brain. Thus, experiments were
      performed to determine the effect of acute and subchronic administration of (+/-)
      3,4-methylenedioxymethamphetamine (MDMA), an amphetamine analog that stimulates 5
      HT release, on alcohol preference in two strains of alcohol-preferring rats, the
      Fawn-Hooded (FH) and alcohol-preferring (P) rats. Rats were individually housed
      and provided free access to a solution of 10% ethanol, food, and water. Ethanol,
      food, and water intakes were measured daily. After establishing a stable baseline
      for ethanol and water intake, each rat was injected SC with a dose of 5.0 mg/kg
      MDMA or an equal volume of saline for 1 or 3 consecutive days. Body temperature
      was recorded immediately before and 120, 240, and 360 min after MDMA treatment.
      Ethanol, food, and water intake were measured for the preceding 24 h. Further, to
      determine the effect of MDMA on alcohol metabolism rats were injected with 5.0
      mg/kg MDMA or saline and 15 min later with 2.5 g/kg alcohol. Then, blood alcohol
      levels were determined at 1, 3, and 5 h after alcohol administration. Our results
      show that a single administration of 5.0 mg/kg MDMA significantly decreased
      ethanol intake in both FH and P rats and increased water intake. Subchronic
      administration of 5.0 mg/kg MDMA for 3 consecutive days significantly attenuated
      alcohol intake in both strains but only increased water intake in P rats.
      Administration of MDMA induced hyper- and hypothermia in FH and P rats,
      respectively. This drug failed to exert any significant effect on the
      pharmacokinetics of alcohol, indicating a central effect.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1357676
TI  - Microinjections of dopamine agonists in the nucleus accumbens increase ethanol
      reinforced responding.
AB  - Long-Evans rats (N = 3) were trained to lever press on a fixed-ratio 4 (FR 4)
      schedule with ethanol (10% v/v) presented as the reinforcer. Each rat received a
      total of six bilateral nucleus accumbens microinjections, one per week. They were
      tested with one physiological saline control, three 20.0-microgram/brain d
      amphetamine, and two 6.0-microgram/brain quinpirole injections given 10 min prior
      to operant sessions. Ethanol-reinforced responding terminated after approximately
      10 min during control sessions. Microinjections of the D2 agonist quinpirole and
      the nonspecific dopamine (DA) agonist d-amphetamine increased total responding
      but produced slowed response rates that continued for 45-60 min. The slowed
      response rate produced by d-amphetamine resulted in a peak increase in
      interresponse times (IRTs) between 8-10 s, whereas quinpirole increased IRTs in
      the 14- to 16-s range, indicating that nonspecific DA activation resulted in
      higher rates of ethanol-reinforced responding than specific D2 activation
      although both drugs decreased local response rates. These data indicate that the
      amount and temporal extent of ethanol-reinforced responding are increased by
      microinjections of DA agonists in the nucleus accumbens and support the
      hypothesis that DA activity in this region is involved in the regulation of
      ethanol-reinforced responding.

PMID- 1357677
TI  - NMDA enhances the central depressant properties of ethanol in mice.
AB  - Male Swiss-Webster mice were used to examine the effect of NMDA on the ethanol
      induced loss of the righting reflex (LORR). The LORR was used as a measure of CNS
      depression. Immediately after animals regained the righting reflex following
      ethanol injection (4.0 g/kg, IP) mice received an ICV injection of saline or NMDA
      (10, 50, 100, or 500 nmol/kg) in a volume of 5 microliters. Upon ICV injection of
      NMDA, mice again lost the righting reflex and this effect of NMDA in the presence
      of ethanol occurred rapidly and in a dose-dependent manner. In another experiment
      DL-2-amino-5-phosphonovaleric acid (APV), a competitive antagonist of NMDA, was
      given ICV with NMDA (50 nmol/kg) in the presence of ethanol. APV (10 and 100
      nmol/kg, ICV) significantly attenuated the response of NMDA to enhance the
      depressant action of ethanol. When bicuculline methiodide, an antagonist of GABA,
      was given ICV with NMDA (50 nmol/kg), bicuculline methiodide reduced the effect
      of NMDA to produce a second loss of the righting reflex (return to the LORR) in
      the presence of ethanol. When NMDA (100 nmol/kg, ICV) was injected in the absence
      of ethanol into mice, NMDA by itself did not produce a loss of the righting
      reflex. In this investigation, the results suggest that NMDA can augment ethanol
      induced depression possibly through an interaction between glutamatergic and
      GABAergeric systems in the CNS.

PMID- 1357678
TI  - Evidence for noradrenergic involvement in mediating the FG 7142 discriminative
      stimulus.
AB  - Rats were trained to discriminate the stimulus properties of the benzodiazepine
      receptor partial inverse agonist beta-carboline-3-carboxylate acid methyl amide
      (FG 7142) (5.0 mg/kg) or the alpha 2-adrenergic receptor antagonist 17 alpha
      hydroxyyohimban-16 alpha-carboxylic acid methyl ester (yohimbine) (3.0 mg/kg)
      from vehicle in a two-lever, food-motivated operant task. These compounds have in
      common a beta-carboline structure and anxiogenic behavioral profiles. The
      yohimbine discriminative stimulus was mimicked by the alpha 2-adrenergic receptor
      antagonist idazoxan and antagonized by the alpha 2-adrenergic receptor agonist
      clonidine, indicating that the yohimbine stimulus was mediated through the alpha
      2-adrenergic receptor. The anxiogenic beta-carbolines FG 7142, 1,2,3,4-tetrahydro
      beta-carboline (THBC), and norharmane, the anxiogenic/convulsant agent
      pentylenetetrazole (PTZ), and two physiological stressors failed to mimic the
      yohimbine discriminative stimulus. In contrast, both yohimbine and idazoxan dose
      responsively mimicked the anxiogenic FG 7142 stimulus. The present results
      demonstrate that an asymmetrical generalization exists between the discriminative
      stimuli produced by yohimbine and FG 7142. Furthermore, these data suggest that
      yohimbine can produce a multicomponent discriminative stimulus, part of which may
      be anxiogenic in nature. The ability of alpha 2-adrenergic receptor antagonists
      to mimic the FG 7142 cue suggests that activation of the noradrenergic system may
      underlie cues produced by benzodiazepine receptor inverse agonists.

PMID- 1357679
TI  - Structure-activity relationship of new 10-13 membered oxygen-nitrogen
      heterocyclic systems containing two aromatic rings.
AB  - The synthesis and biological activity of new 10-13 membered oxygen-nitrogen
      heterocyclic systems condensed with two aromatic rings is reported. The structure
      activity relationship of these new compounds in X-ray investigation has been
      studied. Pharmacological investigations have shown that the compounds exhibit
      weak neuroleptic activity.

PMID- 1357680
TI  - Effects of adrenoceptor agonists and antagonists on cardiovascular functional
      parameters in rats.
AB  - The effects of intravenous administration of adrenoceptor agonists and
      antagonists on electrocardiographic or blood pressure (BP) functional parameters
      were assessed in urethane-anesthetized rats. The responses of cardiovascular
      functional parameters produced by these drugs included: (1) isoproterenol
      decreased the duration of a whole BP cycle (Wd), duration of the diastolic wave
      (Dd), peak amplitude of the systolic wave (SYa), amplitude of the diastolic notch
      (DNa), amplitude of the diastolic wave (DWa), pulse pressure (dp) and mean
      arterial pressure (mp) but increased the heart rate (HR) accompanied by prolonged
      R-R (RR) or P-P interval (PP) (2) propranolol decreased SYa, DNa, dp, mp, HR, the
      amplitude of the P wave (Pa) and amplitude of the S wave (Sa) but increased the
      duration of the QRS wave, P-R interval, duration of the R wave (Rd) and duration
      of the P wave (Pd); (3) adrenaline decreased HR (accompanied by prolonged RR and
      PP), Rd, Pa and amplitude of the T wave (Ta) but increased Pd, Wd, Dd, DNA, the
      time interval between aortic valve opening and closure (Dw), dp, mp, amplitude of
      the Q wave and amplitude of the R wave (Ra); (4) noradrenaline decreased HR
      (accompanied by prolonged RR and PP) and Pa but increased Wd, Pd, SYa, DNa, Dw,
      dp, mp, Ra and Ta; (5) phenylephrine decreased HR (accompanied by prolonged RR
      and PP) and Pa but increased Wd, Dd, DNa, mp and Ra; (6) phentolamine decreased
      SYa, DNa, DWa, Dw, dp and mp. This study illustrates the utility of the automated
      electrocardiogram (ECG) and BP analysis system for investigation of adrenoceptor
      agonists and antagonists. The use of this methodology not only reproduced most of
      cardiovascular functional parameter effects produced by these drugs using the
      conventional methodology but also realizes some new information about the drug
      induced ECG or BP waveform effects.

PMID- 1357682
TI  - The effects of neuroleptics on facial action in schizophrenic patients.
AB  - This paper describes the influence of neuroleptic therapy on facial action in
      drug-naive schizophrenics. In a comparative study of medicated and unmedicated
      schizophrenic patients, the coordinates of 12 small light-reflecting points,
      attached to subjects' faces, were computer-recorded and analyzed automatically
      during a semi-standardized clinical interview. In addition, facial activity in
      videotaped interviews was coded using the Facial Action Coding System (FACS).
      Each sample group comprised of eight patients with the DSM-III-R diagnostic
      criteria "schizophrenia" or "schizophreniform disorder". Subjects were studied on
      two occasions, one shortly after admission to the hospital, the other three weeks
      later. Group 1 was unmedicated during the first session, whereas group 2 was
      medicated throughout the study. Three weeks after the start of medication, at the
      second interview, both recording methods showed a reduction in facial activity
      and facial expression across all subjects in group 1. The facial action of
      patients in group 2, however, remained unchanged.

PMID- 1357681
TI  - Treatment of generalized anxiety disorder: comparison of a new beta-blocking drug
      (CGP 361 A), low-dose neuroleptic (flupenthixol), and placebo.
AB  - In an attempt to evaluate an alternative drug treatment to benzodiazepines in
      generalized anxiety disorders, a placebo controlled trial was carried out with a
      new beta-adrenergic blocker (CPG 361 A). A low-dosage neuroleptic (flupenthixol)
      was included as a reference drug. Depending on the clinical assessment scales the
      placebo treatment resulted in moderate to excellent improvement in 36% to 56% of
      the patients after four weeks of treatment. The active drugs generally had a
      higher improvement range (from 31% to 80%). The global improvement scale was
      found to be better than the other scales in discriminating between placebo (50%
      improvement) and the active drugs (CGP 361 A brought about 78% improvement and
      flupenthixol brought about 80% improvement). However, only for flupenthixol was
      the difference of statistical significance.

PMID- 1357684
TI  - The origin of modern humans and the impact of chronometric dating. Symposium.
      February 26-27, 1992.

PMID- 1357683
TI  - Use of bromocriptine to prevent puerperal lactation during neuroleptic treatment
      of chronic schizophrenia.
AB  - Bromocriptine, the ergotamine alkaloid 2-bromo-alpha-ergocriptine, is known as a
      dopamine D-2 receptor agonist with strong prolactin-lowering actions and
      potential mental side-effects. The case reported here involves a female chronic
      schizophrenic patient in childbed who was treated both with neuroleptics and with
      bromocriptine; the latter was given in order to prevent inappropriate puerperal
      lactation. The described therapeutic regimen succeeded in preventing puerperal
      lactation without exacerbating schizophrenic symptoms. The simultaneous use of
      neuroleptics and bromocriptine was accompanied by monitoring for changes in
      mental status and plasma prolactin level. The high prolactin plasma levels that
      persisted in spite of treatment with bromocriptine would seem to be a reason to
      carry out further research into the mechanism of action of the drug.

PMID- 1357685
TI  - Outlining the problem.

PMID- 1357686
TI  - Uranium-series dating and the origin of modern man.
AB  - Uranium-series dating is based on measurement of the radioactivity of short-lived
      daughter isotopes of uranium formed in samples which initially contained only the
      parent uranium. Materials suitable for U-series dating are found in many
      prehistoric archaeological sites, and include stalagmitic layers (flowstones),
      and spring-deposited travertines. Some marls and calcretes are also datable using
      isochron methods, whereas dates on molluscan shells, bones and teeth are less
      reliable. Ages obtained using alpha counting to determine isotope ratios have
      errors greater than 5%, and can range from 1 to 350 ka. Mass spectrometric
      methods slightly increase the range (0.1-500 ka) but greatly decrease the error
      to less than 1%, making this the optimal method for high-precision dating of the
      origin of modern man.

PMID- 1357687
TI  - Luminescence dating relevant to human origins.
AB  - Luminescence dating provided the first direct and independent evidence that
      anatomically modern humans had a presence in western Asia earlier than is
      consistent with the 'regional continuity' model. The reliability of the result
      concerned, 92 (+/- 5) ka for burnt flints from Qafzeh Cave, is excellent and
      consistent with isochron analysis of the data. Flint dating has also confirmed
      palaeoenvironmental indications that the Mousterian industry in Europe was
      present somewhat earlier than the 100 ka limit previously accepted. Burnt quartz
      and unburnt sediment have also been important in Palaeolithic dating and the
      latter has a particularly high potential.

PMID- 1357688
TI  - Electron spin resonance (ESR) dating of the origin of modern man.
AB  - Many materials found in archaeological sites are able to trap electronic charges
      as a result of bombardment by radioactive radiation from the surrounding
      sediment. The presence of these trapped charges can be detected by electron spin
      resonance (ESR) spectroscopy: the intensity of the ESR signal is a measure of the
      accumulated dose and thus of the age. Tooth enamel is ubiquitous at
      archaeological sites and is well suited for ESR dating, with a precision of about
      10-20%. This method has now been used to date many sites critical to the
      biological and cultural evolution of modern man. Dates for sites in Israel and
      Africa have demonstrated the existence of anatomically modern humans more than
      100 ka ago.

PMID- 1357689
TI  - Pleistocene geochronology and palaeothermometry from protein diagenesis in
      ostrich eggshells: implications for the evolution of modern humans.
AB  - Proteinaceous residues incorporated within the crystal structure of ostrich
      eggshells (OES) are retained without loss over geological time exceeding 10
      million years. Degradation of the polypeptides, including hydrolysis to smaller
      peptide fragments and eventual release of free amino acids, decomposition, and
      racemization and epimerization occur at regular, predictable rates dependent on
      ambient temperature. The extent of isoleucine epimerization (aIle/Ile ratio) in
      OES follows linear first-order reversible kinetics in controlled-temperature
      laboratory simulations of time up to an aIle/Ile ratio in excess of 1.0. The
      hydrolysis of leucine also follows a predictable pattern, but deviates from first
      order kinetics. A nonlinear mathematical model has been developed that adequately
      describes the pattern of leucine hydrolysis through a wide temperature range.
      Arrhenius parameters were derived from laboratory experiments combined with rate
      constant values found for 14C-dated OES from stratified caves in southern Africa.
      These parameters for isoleucine epimerization and leucine hydrolysis differ by
      ca. 10%, allowing the simultaneous solution of the two equations for temperature,
      independent of sample age. Although the uncertainty of the simultaneous
      temperature is relatively high (+/- 10 degrees C), it provides an effective means
      of identifying burned samples. If sample age is known, palaeotemperatures (the
      integrated thermal history experienced by an eggshell as opposed to an
      'instantaneous' temperature) can be calculated with a precision of better than +/
      1 degrees C. The ages of levels at Border Cave, South Africa, from which
      anatomically modern human skeletal remains have been recovered, are dated by the
      extent of isoleucine epimerization in associated OES.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1357690
TI  - Evolution of modern humans: evidence from nuclear DNA polymorphisms.
AB  - Previously we have described studies of the evolution of modern humans based upon
      data for classical genetic markers and for nuclear DNA polymorphisms. Such
      polymorphisms provide a different point of view regarding human evolution than do
      mitochondrial DNA sequences. Here we compare revised dates for major migrations
      of anatomically modern humans, estimated from archaeological data, with
      separations suggested by a genetic tree constructed from classical marker allele
      frequencies. Analyses of DNA polymorphisms have now been extended and compared
      with those of classical markers; genetic trees continue to support the hypothesis
      of an initial African and non-African divergence for modern humans. We have also
      begun testing non-human primates for a set of human DNA polymorphisms. For most
      polymorphisms tested so far, humans share a single allele with other primates;
      such shared alleles are likely to be ancestral. Populations living in humid
      tropical environments have significantly higher frequencies of ancestral alleles
      than do other populations, supporting the hypothesis that natural selection acts
      to maintain high frequencies of particular alleles in some environments.

PMID- 1357691
TI  - New approaches to dating suggest a recent age for the human mtDNA ancestor.
AB  - The most critical and controversial feature of the African origin hypothesis of
      human mitochondrial DNA (mtDNA) evolution is the relatively recent age of about
      200 ka inferred for the human mtDNA ancestor. If this age is wrong, and the
      actual age instead approaches 1 million years ago, then the controversy abates.
      Reliable estimates of the age of the human mtDNA ancestor and the associated
      standard error are therefore crucial. However, more recent estimates of the age
      of the human ancestor rely on comparisons between human and chimpanzee mtDNAs
      that may not be reliable and for which standard errors are difficult to
      calculate. We present here two approaches for deriving an intraspecific
      calibration of the rate of human mtDNA sequence evolution that allow standard
      errors to be readily calculated. The estimates resulting from these two
      approaches for the age of the human mtDNA ancestor (and approximate 95%
      confidence intervals) are 133 (63-356) and 137 (63-416) ka ago. These results
      provide the strongest evidence yet for a relatively recent origin of the human
      mtDNA ancestor.

PMID- 1357692
TI  - Southern Africa and modern human origins.
AB  - This paper argues that southern Africa was a remote part of the Old World in the
      late Pleistocene (125-10 ka ago). Because of this isolated position there was
      continuity without significant replacement in the resident population. Isolation
      and the relatively recent spread of agriculture to the region has allowed a
      section of this population to survive into the present. They are the Bushmen
      (San). Studies of geographic patterning in conventional genetic markers and
      mitochondrial DNA indicate that the Bushman clade has a long evolutionary history
      in southern Africa. Estimates of more than 100 ka for the continued presence of
      this population in the region are supported in archaeological investigations of
      sites with long sequences such as Klasies River main site and Border Cave. Human
      remains dating to the earlier part of the late Pleistocene have been recovered
      from these sites and the samples form a morphological series with the Klasies
      River remains possibly 20 ka older than those from Border Cave. There is no
      fossil record for the later Pleistocene, however, at a period when selection for
      a gracile morphology may have been pronounced. The cultural associations in the
      earlier late Pleistocene are with the Middle Stone Age. Expressions of cultural
      'style' and the occurrence of similar artefact design types in the Middle and
      Later Stone Ages can be interpreted with reference to the ethnographic present.
      Temporal continuity can be shown in the geographical distribution of stylistic
      markers and this suggests participation in a shared cognitive system.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1357693
TI  - Recent human evolution in northwestern Africa.
AB  - The first modern humans in the Maghreb are said to be associated with the Aterian
      industries which appeared at least 40 ka BP in the northwest. Their predecessors
      are mainly represented by the Jebel Irhoud (Morocco) specimens. Palaeontological
      evidence, as well as electron spin resonance (ESR) dating, suggests that this
      series is older than previously published, and should belong to oxygen isotope
      stage 5 or even 6. There is no evidence of any Neanderthal apomorphy in this
      group which can no longer be considered as 'African Nanderthals'. Clear
      synapomorphies with modern man combined with some plesiomorphic retentions
      indicate a slightly more primitive (and older?) grade than the Qafzeh-Skhul
      sample in southwestern Asia. The Northwestern evidence demonstrates that the
      mediterranean sea was a major biological barrier during the upper Middle and
      lower Upper Pleistocene and that the rise of anatomically modern features cannot
      be restricted to a sub-Saharan of eastern African area.

PMID- 1357694
TI  - The role of western Asia in modern human origins.
AB  - Western Asia provides the best collection of human skeletal remains relevant to
      the two basic models for the emergence of modern humans, namely the 'rapid
      replacement' and the 'regional continuity' models. Regardless of the taxonomies
      of particular hominids, their chronology is of crucial importance.
      Thermoluminescence (TL) and electron spin resonance (ESR) dates demonstrate that
      the Acheulo-Yabrudian and Mousterian entities and their associated fossils
      (Zuttiyeh, Tabun, Skhul, Qafzeh, Kebara, Shanidar, Amud) span the late Middle and
      Upper Pleistocene period. These new dates initiated major chronological revisions
      and renewed discussion of the cultural-archaeological implications. One of the
      most important conclusions is that the Middle to Upper Palaeolithic transition
      (or Revolution) 45-40 ka ago has nothing to do with the appearance of
      anatomically early modern humans in western Asia, which occurred some 100 ka ago
      or more. The Levant, the coastal region of the eastern Mediterranean, was both a
      corridor for movement of humans and animals as well as a refugium during
      climatically harsh periods. The mixture of morphological characteristics among
      the available Middle Palaeolithic human fossils is interpreted as reflecting the
      presence of immigrant and local populations. Archaeologically observable
      behavioural changes are taken as hints to the pre-adaptations of the Middle to
      Upper Palaeolithic revolution. The archaeological record of western Asia can
      contribute significantly to explaining the Middle to Upper Palaeolithic
      revolution. This region was the core area where the 'Neolithic Revolution' took
      place. The shift to systematic cultivation and the domestication of animals
      occurred within a short time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357695
TI  - African and Asian perspectives on the origins of modern humans.
AB  - The ways in which the cultural evidence - in its chronological context - can be
      used to imply behavioural patterning and to identify possible causes of change
      are discussed. Improved reliability in dating methods, suites of dates from
      different regional localities, and new, firmly dated fossil hominids from crucial
      regions such as northeast Africa, the Levant, India and China, are essential for
      clarification of the origin and spread of the modern genepool. Hominid ancestry
      in Africa is reviewed, as well as the claims for an independent origin in Asia.
      The cultural differences and changes within Africa, West and South Asia and the
      Far East in the later Middle and early Upper Pleistocene are examined and
      compared, and some behavioural implications are suggested, taking account of the
      evolutionary frameworks suggested by the 'multiregional evolution' and 'Noah's
      Ark' hypotheses of human evolution. A possible explanation is proposed for the
      cultural differences between Africa, West Asia and India on the one hand, and
      southeast Asia and the Far East on the other. The apparent hiatus between the
      appearance of the first anatomically modern humans, ca. 100 ka ago, and the
      appearance of the Upper Palaeolithic and other contemporaneous technological and
      behavioural changes around 40 ka ago, is discussed. It is suggested that the
      anatomical changes occurred first, and that neurological changes permitted the
      development of fully syntactic language some 50 ka later. The intellectual and
      behavioural revolution, best demonstrated by the 'Upper Palaeolithic' of Eurasia,
      seems to have been dependent on this linguistic development - within the modern
      genepool - and triggered the rapid migration of human populations throughout the
      Old World.

PMID- 1357696
TI  - Reconstructing recent human evolution.
AB  - The two most distinct models of recent human evolution, the multiregional and the
      recent African origin models, have different retrodictions concerning specific
      archaic-recent population relationships. The former model infers multiple
      regional archaic-modern connections and the ancient establishment of regional
      characteristics, whereas the latter model implies only an African archaic-all
      modern relationship, with recent (late Pleistocene) development of regionality.
      In this paper, four late archaic groups from Europe, southwest Asia, Africa and
      East Asia are compared with various fossil and recent Homo sapiens crania or
      cranial samples. The results of Penrose shape comparisons narrowly favour a late
      archaic African-modern special relationship over an East Asian-modern one, with
      European and southwest Asian Neanderthal groups much more distant. No specific
      archaic-recent regional relationships are indicated in the shape analyses, nor in
      separate examinations of patterns of regionality, which indicate a recent origin
      for present day regionality. The Skhul-Qafzeh sample provides an excellent shape
      intermediate between the archaic and recent samples.

PMID- 1357697
TI  - Archaeology and the population-dispersal hypothesis of modern human origins in
      Europe.
AB  - The transition from anatomically 'archaic' to 'modern' populations would seem to
      have occurred in most regions of Europe broadly between ca. 40 and 30 ka ago:
      much later than in most other areas of the world. The archaeological evidence
      supports the view that this transition was associated with the dispersal of new
      human populations into Europe, equipped with a new technology ('Aurignacian') and
      a range of radical behavioural and cultural innovations which collectively define
      the 'Middle-Upper Palaeolithic transition'. In several regions of Europe there is
      archaeological evidence for a chronological overlap between these populations and
      the final Neanderthal populations and, apparently, for various forms of contact,
      interaction and, apparently, 'acculturation' between these two populations. The
      fundamental behavioural adaptations implicit in the 'Upper Palaeolithic
      Revolution' (possibly including language) are thought to have been responsible
      for this rapid dispersal of human populations over the ecologically demanding
      environments of last-glacial Europe.

PMID- 1357698
TI  - Recent human evolution in East Asia and Australasia.
AB  - In both East Asia and Australasia arguments for evolutionary continuity between
      middle-late Pleistocene hominid populations and modern Homo sapiens are of long
      standing. In both regions, however, problems of chronological distribution,
      dating and preservation of hominid skeletal materials provide an effective
      barrier to extending regional sequences back to 'archaic' Homo sapiens or Homo
      erectus. The earliest securely dated modern Homo sapiens in East Asia are
      currently represented by Zhoukoudian Upper Cave at a minimum of 29 ka BP. In
      Australia skeletal remains of modern Homo sapiens have been dated to 26 ka BP,
      with archaeological materials at 38 to 50 ka BP. Late Pleistocene human skeletons
      from sites like Coobool Creek are morphologically and metrically outside the
      range of recent Australian Aboriginal populations. Similarly Liujiang and the
      Upper Cave crania can be distinguished from recent East Asian 'Mongoloids'.
      Evolutionary change within the Holocene needs to be taken into consideration when
      the evidence for regional evolutionary continuity is considered.

PMID- 1357699
TI  - Models and realities in modern human origins: the African fossil evidence.
AB  - The recent application of such chronometric techniques as electron spin resonance
      (ESR), thermoluminescence (TL), and uranium series dating has had a significant
      impact on perceptions of modern human origins. Claims for the presence of
      anatomically modern humans in Africa prior to 100 ka and for the transition
      leading to modern Africans at an even earlier date have been made, partly based
      on results of these techniques. However, a careful examination of the pertinent
      record shows that these claims are not unequivocally supported by the available
      fossil and chronological evidence.

PMID- 1357700
TI  - Effects of adrenalectomy and deprivation condition on food intake after
      phenylpropanolamine or clonidine.
AB  - alpha-Adrenergic receptors within the paraventricular hypothalamus (PVN) modulate
      feeding such that activation of alpha 2-adrenoceptors by drugs such as clonidine
      (CLON) increase feeding; whereas activation of alpha 1-adrenoceptors by drugs
      such as phenylpropanolamine (PPA) suppress feeding. Prior studies suggest that
      the feeding-stimulatory effect of alpha 2-adrenergic activation is a function of
      drug dose as well as the deprivation condition and adrenal status of the animal.
      Specifically, CLON's effects on feeding are greatest at low doses in food
      satiated adrenally intact rats. Whether a similar profile is produced by alpha 1
      adrenoceptor agonists such as PPA has not previously been explored. Thus, the
      present study provides a comparison of the effects on food intake of drug dose,
      deprivation condition, and adrenalectomy induced by these alpha 2- and alpha 1
      adrenergic drugs. Accordingly, both adrenalectomized (ADX) as well as sham
      control (SHAM) adult male rats underwent a series of 1-h feeding tests following
      administration of PPA (5, 10, 20 mg/kg, IP) as well as CLON (0.0125, 0.025, 0.05,
      0.1 mg/kg, IP) under both deprived and nondeprived testing conditions. The
      results suggest that the deprivation condition, but not the surgical condition
      (ADX vs. SHAM), exerts the greatest overall effect on food intake following
      administration of alpha-adrenergic drugs.

PMID- 1357701
TI  - Treatment of tardive dyskinesia with ceruletide: a double-blind, placebo
      controlled study.
AB  - The effectiveness of a once-weekly i.m. injection of ceruletide (0.8
      microgram/kg) in suppressing the symptoms of neuroleptic-induced tardive
      dyskinesia (TD) was evaluated in a double-blind, placebo-controlled, matched
      pairs study. Global evaluation of the severity of TD symptoms over the 8-week
      study period revealed a significant improvement with ceruletide as compared with
      placebo. Analysis of the therapeutic response to ceruletide over the course of
      treatment revealed a slow, but long-lasting improvement of TD symptoms. Side
      effects, which were mild and transient, consisted mainly of nausea and epigastric
      discomfort. The incidence of side effects did not differ between the ceruletide-
      and placebo-treated groups. Ceruletide appears to be a novel and practical
      treatment that can substantially alleviate the symptoms of dyskinesia.

PMID- 1357702
TI  - Cerebrospinal fluid and serum levels of neuron-specific enolase in patients with
      schizophrenia.
AB  - Some patients with schizophrenia appear to have brain abnormalities, including
      enlarged third and lateral ventricles and reduced volumes of temporal lobe
      structures. These abnormalities could be attributed to a developmental
      abnormality or a neurodegenerative process. Neuron-specific enolase (NSE), a
      protein that is found primarily in neurons and neuroendocrine cells, has been
      used as an index of neuronal damage or degeneration. Levels of NSE in
      cerebrospinal fluid (CSF) and serum from 50 patients with acute and chronic
      schizophrenia were compared with those in normal and neurological control
      subjects. A double-antibody, solid phase iodinated radioimmunoassay was used to
      determine NSE levels. There was no evidence of elevated levels in patients with
      schizophrenia, whereas control subjects with neurological illnesses had increased
      levels of NSE in CSF. Because NSE is rapidly cleared from CSF, however, elevated
      levels could have been missed. Unmedicated patients tended to have lower levels
      than medicated patients.

PMID- 1357703
TI  - A two-year prospective study of treatment compliance in patients with
      schizophrenia.
AB  - The study is a prospective investigation of the factors associated with treatment
      compliance in 61 patients discharged from hospital with a ward diagnosis of
      schizophrenia. All cases were classified using reliable diagnostic criteria and
      all were followed up for two years. Compliance was assessed by inspection of
      records and by analysis of urine. Sociodemographic factors and illness variables
      were unrelated to compliance. Some aspects of a patient's insight and attitude,
      namely, a belief that medication had helped during the admission, a stated
      willingness to take treatment after discharge and a generally optimistic outlook,
      were associated with improved compliance. Other variables which showed such an
      association were the absence of the drug side-effect akinesia, good previous
      compliance and voluntary, as opposed to compulsory, admission to hospital.

PMID- 1357704
TI  - Alpha-2 adrenergic agonists decrease distractibility in aged monkeys performing
      the delayed response task.
AB  - With advancing age, monkeys become impaired on a test of spatial working memory,
      the delayed response task, and show increased susceptibility to interference from
      irrelevant stimuli (Bartus and Dean 1979). Alpha-2 adrenergic agonists such as
      clonidine and guanfacine have been shown to improve the delayed response
      performance of aged monkeys under standard testing conditions (e.g. Arnsten et
      al. 1988). The current study examined whether these drugs could protect the
      delayed response performance of aged monkeys when irrelevant stimuli were
      presented during the delay intervals. Aged monkeys were tested on the variable
      delayed response task with short delays to minimize memory demands and optimize
      performance on control (no interference) sessions. During interference sessions,
      distractors were presented during the delays on 9 of the 30 trials ("distractor"
      trials). If the aged monkeys had been pretreated with saline, performance was
      significantly disrupted by the irrelevant stimuli compared to matched saline
      control sessions. This impairment was not only evident on the 9 distractor
      trials, but on the 21 remaining "nondistractor" trials as well. However, if the
      aged monkeys had been pretreated with clonidine or guanfacine, performance was
      not impaired on the interference sessions. This beneficial effect of the alpha-2
      agonists was most apparent on the nondistractor trials. Guanfacine was able to
      decrease the harmful effects of distraction without any apparent sedative side
      effects. Co-administration of the alpha-2 antagonists idazoxan or SKF104078 with
      clonidine blocked the protective effects of the agonist on delayed response
      performance, consistent with actions at alpha-2 adrenergic receptors. These
      findings suggest that alpha-2 agonists improve delayed response performance, at
      least in part, by helping to protect memory from irrelevant stimulation.
      Clonidine is already used in the treatment of Attention Deficit Disorder, and the
      current data suggest that guanfacine may also be useful in this regard.

PMID- 1357705
TI  - Morphine withdrawal aggression: modification with D1 and D2 receptor agonists.
AB  - Morphine withdrawal increases aggressive behaviors, induces explosive motor
      behaviors, and disrupts homeostatic functions in mice and rats. While many of
      these effects appear to result from altered dopaminergic activity during morphine
      withdrawal, the relative contributions of the D1 and D2 receptor subtypes remain
      unclear. In the present experiments, the D1 agonist SKF 38393 and the D2 agonist
      quinpirole were administered to male "resident" Swiss-Webster mice 5 h after the
      removal of a subcutaneously-implanted morphine or placebo pellet. These mice were
      then observed alone to determine changes in various motor activities and in
      confrontation with a group-housed male "intruder" to assess changes in aggressive
      behaviors. SKF 38393 decreased the display of aggressive behaviors by placebo and
      morphine-withdrawn mice without consistently altering walking or rearing.
      Quinpirole greatly decreased the display of aggressive behaviors by placebo mice
      and decreased aggressive behaviors in morphine-withdrawn mice to a lesser degree.
      The inhibitory effects of quinpirole were not specific to aggressive behaviors;
      low quinpirole doses also decreased the display of walking and rearing. In mice
      which received a low dose of SKF 38393 preceding quinpirole injection,
      pretreatment with the D1 agonist did not alter the effects of the D2 agonist
      quinpirole on motor activities but maintained high levels of aggression in
      morphine-withdrawn mice. The differential modification of aggressive and motor
      behaviors by selective dopaminergic agonists during morphine withdrawal further
      supports the suggestion that aggressive and motor behaviors are controlled
      independently; furthermore, D1 receptor stimulation appears to have particular
      relevance for the display of aggressive behaviors during morphine withdrawal.

PMID- 1357707
TI  - Chronic imipramine treatment normalizes levels of tyrosine hydroxylase in the
      locus coeruleus of chronically stressed rats.
AB  - Previous studies have demonstrated that chronic stress increases and
      antidepressant treatments decrease levels of tyrosine hydroxylase (TH) in locus
      coeruleus (LC). In the present study, the influence of chronic antidepressant
      treatment on the induction of TH immunoreactivity in response to cold stress is
      examined. It was found that chronic imipramine pretreatment (18 days) attenuated
      the induction of TH in response to cold stress, resulting in levels of TH
      immunoreactivity not different from control. In contrast, imipramine pretreatment
      for 1 or 7 days was not sufficient to normalize the stress-induced elevation of
      TH immunoreactivity. These findings raise the possibility that the therapeutic
      action of antidepressants may be derived, in part, from the ability of these
      treatments to normalize levels of TH and thereby the function of the NE
      neurotransmitter system under conditions of stress.

PMID- 1357706
TI  - Dexmedetomidine synergism with midazolam in the elevated plus-maze test in rats.
AB  - The anxiolytic profile of dexmedetomidine, a novel, highly-selective alpha 2
      adrenergic agonist, was examined in rats in the elevated plus-maze test when
      administered either alone or in combination with the benzodiazepine agonist
      midazolam. Dexmedetomidine, 0.1-10 micrograms/kg, was inactive in modifying the
      rats' behavioral response in this test. Midazolam, 0.1-10 mg/kg, dose-dependently
      produced an anxiolytic-like profile characterized by an increased time spent in
      the open arms of the elevated plus-maze. A combination of dexmedetomidine 0.5
      micrograms/kg and midazolam 0.5 mg/kg produced a synergistic interaction. This
      heterergic interaction of dexmedetomidine on midazolam's anxiolytic-like profile
      was dose-dependently blocked by pretreatment with an alpha 2-adrenergic
      antagonist, atipamezole, 10-50 micrograms/kg, and a benzodiazepine antagonist
      flumazenil, 1.0 and 10 mg/kg, but not by the alpha 1-adrenergic antagonist,
      prazosin, 0.1-10 mg/kg. While the transmembrane signal transduction pathways for
      benzodiazepine- and alpha 2-agonist responses do not share any molecular
      component, there does appear to be "crosstalk" between these two systems. These
      may involve GABA or noradrenergic "downstream" effects of either dexmedetomidine
      or midazolam, respectively.

PMID- 1357708
TI  - Kappa opioid receptor activity modulates memory for peck-avoidance training in
      the 2-day-old chick.
AB  - To examine the role of kappa opioid receptors in memory formation, 2-day-old
      chicks were injected intracerebrally with either the endogenous opioid peptide
      dynorphin(1-13), the highly kappa selective agonist U-50,488 or the kappa
      selective antagonist nor-binaltorphimine (nor-BNI), given one-trial peck
      avoidance training, and tested 24 h later. Dynorphin(1-13) impaired memory in a
      dose dependent manner at 24 h test. Injection of U-50,488 caused a biphasic dose
      dependent effect on memory; low doses caused a trend toward enhanced memory and
      high doses caused significant impairment. Conversely, injection of low doses of
      nor-BNI caused a trend toward memory impairment, and higher doses caused
      significant memory enhancement. The results indicate that memory formation for
      one-trial peck-avoidance training may be modulated by kappa opioid receptor
      activity.

PMID- 1357709
TI  - 5-HT1A receptor agonists prevent in rats the yawning and penile erections induced
      by direct dopamine agonists.
AB  - The new compound (+) S-20499, an amino chromane derivative (8[-4[N-(5
      methoxychromane-3yl)N-propyl]aminobutyl] azaspiro[4-5] decane-7,9 dione), is a
      high affinity full 5-HT1A agonist. We have investigated its effects on
      dopaminergic transmission. (+) S-20499 displayed a 10(-8) M affinity for D2
      dopamine (DA) receptors, 100 fold lower than for 5-HT1A receptors. The
      hypothermic effect of the drug was reversed by haloperidol in mice, suggesting
      that it behaves as a direct dopamine agonist. However, increasing doses of (+) S
      20499 induced neither yawning nor penile erections, which constitute
      characteristic responses of direct DA agonists administered at low doses. In
      addition, (+) S-20499 prevented the apomorphine (100 micrograms/kg SC) induced
      yawning and penile erections. This inhibition appears to result from the
      stimulation of 5-HT1A receptors since it is an effect shared by both buspirone
      (from 5 mg/kg) and 8-OH-DPAT (from 0.10 mg/kg). In addition, when rats are
      treated with the 5-HT1A receptor antagonist tertatolol (2-5 mg/kg; SC),
      increasing doses of (+) S-20499 elicit the expected yawns and penile erections.
      It is concluded that the 5-HT1A agonist property opposes to that of D2 dopamine
      receptor stimulation with regard to yawning and penile erections.

PMID- 1357710
TI  - Delayed-non-match-to-sample performance in the radial arm maze: effects of
      dopaminergic and gabaergic agents.
AB  - Central dopaminergic transmission has been implicated in memory processes. The
      present experiments examined the effects of several direct acting dopaminergic
      agents on performance of a delayed-non-match-to-sample radial arm maze task.
      Preadministration of apomorphine (D1-D2 agonist; 0.25, 0.5, and 1.0 mg/kg),
      quinpirole (D2 agonist; 0.1 mg/kg), or SKF38393 (D1 agonist; 3 mg/kg) increased
      the latency of choices but did not affect any index of accuracy with a 1 h
      retention interval. Post-training administration of quinpirole (0.1, 0.2, 1.0,
      and 2.0 mg/kg), SKF38393 (0.3, 3.0, and 6.0 mg/kg), sulpiride (D2 antagonist; 3,
      10, and 30 mg/kg), or SCH23390 (D1 antagonist; 0.01, 0.1, and 1.0 mg/kg) also did
      not affect accuracy, although quinpirole produced a dose-dependent increase in
      the latency of choices, assessed 10 h post-treatment. For comparison, pretraining
      and post-training administration of the benzodiazepine chlordiazepoxide (1, 3, 5
      mg/kg) was also tested and produced dose-dependent impairments in mnemonic
      performance at either a 1 or 4 h retention interval. The effects of
      chlordiazepoxide are consistent with evidence indicating that GABAergic agents
      can influence memory processes. In contrast, the present findings indicate that
      (peripheral administration of dopaminergic agents IS) not sufficient to alter the
      mnemonic processes required for accurate performance of this DNMTS-RAM task.

PMID- 1357711
TI  - Discriminative stimulus properties of 8-OH-DPAT: relationship to affinity for
      5HT1A receptors.
AB  - Previous studies have shown that discriminative stimulus control established with
      the 5HT1A receptor agonist, 8-OH-DPAT, generalizes to other 5HT1A agonists and
      partial agonists but also to the alpha 2-adrenoceptor antagonist, yohimbine. On
      the basis of these results it has been proposed that the 8-OH-DPAT cue may be
      produced by activity at more than one receptor. In the present study rats were
      trained to discriminate a dose of 8-OH-DPAT (0.05 mg/kg, SC) from saline.
      Substitution tests showed dose-dependent generalisation with the 5HT1A compounds,
      buspirone, ipsapirone, MDL 72832 and MDL 73005EF, the alpha 2-adrenoceptor
      antagonists, yohimbine and idazoxan, and BMY 14802, which is usually described as
      a sigma ligand. The buspirone metabolite 1-pyrimidinyl piperazine (1-PP) which
      possesses mainly alpha 2-adrenoceptor antagonist properties produced only partial
      generalisation which was not dose related. Receptor binding studies showed that
      all the compounds which substituted for 8-OH-DPAT displaced [3H]-8-OH-DPAT
      binding to rat hippocampal membranes. Furthermore, there were statistically
      significant positive correlations between drug affinity for 5HT1A sites and their
      ED50 values for both substitution for 8-OH-DPAT and potency to decrease response
      rates. These results are consistent with the view that the 8-OH-DPAT cue, like
      the ability of the compounds tested to decrease rates of responding, is largely
      mediated by activity at 5HT1A receptors.

PMID- 1357712
TI  - Changes in dopa decarboxylase mRNA but not tyrosine hydroxylase mRNA levels in
      rat brain following antipsychotic treatment.
AB  - The effects of antipsychotic administration (1-32 days, twice per day) on the
      levels of mRNA coding for dopa decarboxylase (DDC) and tyrosine hydroxylase (TH)
      in rat brain has been assessed by a procedure utilising solution hybridisation
      with oligonucleotides. Saline and sulpiride (20 mg/kg/day) had no apparent effect
      on DDC mRNA levels. Haloperidol (3 mg/kg/day) elicited increases in DDC mRNA
      levels of 240% after 32 days and loxapine (4 mg/kg/day) elicited increases of
      180% in DDC mRNA levels. None of the drugs affected TH mRNA levels. These results
      indicate that DDC may be more important than TH in the long term regulation of
      dopamine production.

PMID- 1357715
TI  - Kuopio Declaration on Health Research and Human Development.

PMID- 1357714
TI  - Pseudocyesis in organic mood disorders. Six cases.
AB  - Pseudocyesis, the delusion of pregnancy, has had an uncertain nosology, primarily
      because of the concentration on the content of the beliefs and lack of interest
      in the underlying phenomenology. Six patients with a major mood disorder caused
      by cerebral dysfunction are presented in this article. The delusion is reviewed
      with respect to the entities it overlaps, and the clinical manifestations are
      related to the mood disorders. Although no clear neuroanatomic localization was
      possible with this group of patients, there may be some association with
      desomatization caused by parietal lobe dysfunction.

PMID- 1357716
TI  - [The structural-functional organization of the bone marrow after lethal
      irradiation and the transplantation of syngeneic hematopoietic cells].
AB  - A study was made of the content and morphology of haemopoietic islands in the
      bone marrow of lethally irradiated CBA mice, and their change after
      transplantation of syngeneic haemopoietic cells. The data obtained show that the
      haemopoietic islands are reconstructed in the injured haemopoietic tissue due to
      the donor's bone-marrow nuclears. A new type of structural and functional
      associations, namely, stromal haemopoietic islands, has been found.

PMID- 1357717
TI  - Circumventricular organs and brain fluid environment: molecular and functional
      aspects. Proceedings of the 4th Reinhardsbrunn Symposium. Leipzig, Germany, March
      24-29, 1991.

PMID- 1357718
TI  - Blood-brain barrier: a molecular approach to its structural and functional
      characterization.
AB  - Our approach to analyze molecular components of the blood-brain barrier led to
      the identification of additional transcripts which can be regarded as "BBB
      markers". Other candidates are presently analyzed in order to find hitherto
      unknown cell type-specific transcripts. We investigated the expression of these
      marker-genes in cell culture and found all genes still being transcribed after 10
      days in primary cultures, although at a lower level. This is surprising, since
      other authors report the disappearance of BBB characteristics under such
      conditions. Moreover, the BBB marker gamma-GT is found to be not only expressed
      in BMEC, but also in the closely associated pericytes. The hitherto unknown
      physiological function of the enzyme, especially the abundance in pericytes is
      still under investigation. Since the method of subtractive cloning has been
      proven as a fruitful approach, we consider to establish further subtractive cDNA
      libraries, using different subtraction parameters. The PCR method is applicable
      for amplification of subtracted cDNA (Timblin et al., 1990) and we expect to find
      additional clones, mainly of lower abundance which are of functional importance
      for the BBB phenomenon. The described characterization of cultured BMEC now
      allows to proceed to study BBB-specific gene expression with special regard to
      regulatory elements. We will perform these experiments by use of enhancer trap
      vectors transfected into BMEC. The isolation of the corresponding genomic DNA
      fragments of the BBB markers is in progress.

PMID- 1357713
TI  - Nicotinic systems and cognitive function.
AB  - Nicotinic acetylcholine receptors have been found to be important for maintaining
      optimal performance on a variety of cognitive tasks. In humans, nicotine-induced
      improvement of rapid information processing is particularly well documented. In
      experimental animals nicotine has been found to improve learning and memory on a
      variety of tasks, while the nicotinic antagonist mecamylamine has been found to
      impair memory performance. Nicotine has been found to be effective in attenuating
      memory deficits resulting from lesions of the septohippocampal pathway or aging
      in experimental animals. Nicotinic receptors are decreased in the cortex of
      patients with Alzheimer's disease. Preliminary studies have found that some
      aspects of the cognitive deficit in Alzheimer's disease can be attenuated by
      nicotine. Nicotine may prove to be useful therapeutic treatment for this and
      other types of dementia.

PMID- 1357719
TI  - Development of an in vitro cell culture system to mimic the blood-brain barrier.
AB  - Primary cultures of brain capillary endothelial cells (BCECs) cocultured together
      with astroglia cells were used to investigate the induction of blood-brain
      barrier (BBB) characteristics in vitro. By immunofluorescence, histochemical
      staining, two-dimensional gel electrophoresis and enzyme activity tests we are
      able to show that BCECs in vitro loose typical blood-brain barrier properties but
      not their common endothelial phenotype. Astrocytes induce the expression of the
      blood-brain barrier characteristic enzymes gamma-glutamyltranspeptidase and
      alkaline phosphatase but only in a coculture system with direct cell to cell
      contact between BCECs and astroglia cells. C6-glioma cells also re-establish the
      BBB phenotype but were less effective compared to astrocytes. The susceptibility
      of the BCECs to an astroglial stimulus depends on the proliferative state of the
      BCECs.

PMID- 1357720
TI  - Bidirectional passage of peptides across the blood-brain barrier.

PMID- 1357721
TI  - Regulation of transendothelial transport in the cerebral microvessels: the role
      of second messengers-generating systems.
AB  - Different elements of the intracellular signaling messenger systems have been
      detected in the course of our studies in the cerebral endothelial cells. It has
      been shown that the synthesizing enzymes of and substrate proteins for the second
      messenger molecules are present in the cerebral endothelial cells, and their
      activity and/or amount can change in pathological circumstances, i.e., during the
      formation of brain oedema. Pharmacological treatments interfering with the second
      messenger systems proved to be effective in the prevention of brain oedema
      formation.

PMID- 1357722
TI  - Somatostatin-binding sites on structures of circumventricular organs.

PMID- 1357723
TI  - Neuropeptides in the cerebrospinal fluid and regulation of behavior.

PMID- 1357724
TI  - Sulfasalazine inhibits lyso-PAF: acetyl-COA acetyltransferase.
AB  - Sulfasalazine produced a dose-dependent inhibition of the enzymatic synthesis of
      platelet-activating factor (PAF) in lysates of rat pleural neutrophils, with an
      IC50 of 50 microM. Major metabolites of sulfasalazine, 5-aminosalicylic acid and
      sulfapyridine, inhibited this enzymatic synthesis at much higher concentrations.
      Inhibition of arachidonate 5-lipoxygenase by sulfasalazine and its major
      metabolites was also observed at higher concentrations (2-3 mM). Because PAF is a
      potent mediator of inflammatory responses, an inhibition of PAF synthesis by
      sulfasalazine may contribute to its therapeutic actions in conditions such as
      ulcerative colitis and rheumatic illnesses.

PMID- 1357725
TI  - Conventional external irradiation alone as adjuvant treatment in resectable
      pancreatic cancer: results of a prospective study.
AB  - Between 1/85 and 1/90, 14 consecutive patients were entered into a prospective
      study of conventional adjuvant post-operative external beam radiotherapy after
      complete resection for a pancreatic adenocarcinoma. The surgical procedure was a
      Whipple resection in nine patients, a distal pancreatectomy in four patients and
      a total pancreatectomy in one patient. There were three T1b, eight T2 and three
      T3 tumours (UICC 1987); nodal involvement was present in five cases. The
      radiotherapy was delivered using a four-field box technique with a 23 x MV photon
      beam. All patients received a total dose of 54 Gy to the tumour bed. The mean
      treated volume was 900 cm3. Acute toxicities consisted mainly of weight loss
      (mean: 2 kg). Two patients had a grade 2 diarrhoea and two patients a grade 2
      gastritis. Late effects were minimal and only observed in two patients. The
      overall locoregional recurrence (LR) rate was 50%. The median disease-free
      survival was 12 months, and the median survival was 23 months. This post
      operative conventional radiotherapy treatment gives results that are comparable
      to the results of the GITSG-adjuvant study using a combination of split-course
      radiotherapy and 5-fluorouracil (5-FU).

PMID- 1357726
TI  - Phenotype of a Rhizobium leguminosarum ntrC mutant.
AB  - A Tn5 insertion mutant, strain CFN2012, of Rhizobium leguminosarum biovar
      phaseoli devoid of glutamine synthetase II (GSII) activity was analysed. It was
      shown to contain Tn5 within an 11-kb BamHI DNA fragment, which was isolated
      (pSM261) from the wild-type strain and, when introduced into strain CFN2012, was
      shown to complement the absence of GSII activity. The DNA sequence of the
      corresponding region from the wild-type allele revealed the presence of an ntrC
      regulatory gene, and restriction analysis indicated that the mutant allele
      carried the Tn5 insertion within it. Further analysis of strain CFN2012 indicated
      that this mutant has reduced levels of the PII regulatory protein and that, in
      contrast to ntrC mutants of other Rhizobiaceae, it grows on nitrate as the sole
      nitrogen source.

PMID- 1357727
TI  - [Shock during combined administration of diltiazem and adrenergic beta receptor
      blockaders].

PMID- 1357728
TI  - [Choroid papilloma in periarteritis nodosa].

PMID- 1357729
TI  - [Iatrogenic neuropathies].
AB  - During the last few years the list of drugs capable of inducing a iatrogenic
      neuropathy has been considerably lengthened. Drug toxicity to peripheral nerves
      may be discovered at the experimental stage, but it is usually recognized after
      the drug has been launched on the market, hence the importance of
      pharmacovigilance. The responsibility of a drug for the occurrence of neuropathy
      may be difficult to prove, particularly when the drug is used in the treatment of
      a disease which, by itself, may be responsible for a lesion of the peripheral
      nervous system. Iatrogenic neuropathies are usually axonal, but some drugs
      produce a primary disorder in the myelin-Schwann cell couple. Schwann cell
      diseases may be induced by drugs, such as perhexiline maleate, amiodarone or
      chloroquine, which inhibit lysosomal enzyme activity. In such cases inclusions
      representing fat-loaded lysosomes can be detected in various tissues, and
      particularly in Schwann cells. In certain patients, notably those treated with
      gold salts, an immune mechanism might be responsible for neuropathy. Most drug
      induced neuropathies are due to a primary lesion of the neuron which is more
      often an axonopathy than a neuronopathy. It is usually a retrograde distal
      axonopathy the occurrence of which is attributed to a disorder of the fast
      retrograde axonal flow. In a few cases, the finding of a biochemical mechanism
      perturbing the axonal flow may help in preventing the occurrence of a iatrogenic
      neuropathy.

PMID- 1357730
TI  - [Atrioventricular block in 2 patients with hemorrhagic fever and renal syndrome
      (Hantaan-virus nephropathy)].

PMID- 1357731
TI  - [Molecular pharmacology in the service of therapeutics. III. The allosteric
      modulation of receptors and the action of benzodiazepines].

PMID- 1357732
TI  - [Molecular pharmacology in the service of therapeutics. II. Inhibitors of the
      renin-angiotensin system].

PMID- 1357733
TI  - [Current status of pathophysiological findings in migraine: facts and
      hypotheses].

PMID- 1357735
TI  - [Global approach to the treatment of chronic asthma in adults].
AB  - The reduction of the bronchial inflammatory reaction, in itself a triggering
      event for bronchospasm, is one of the main targets for treatment in bronchial
      asthma. An early engagement of anti-inflammatory agents is, therefore, as
      necessary for long-term treatment as the reduction of irritating or antigenic
      environmental factors. Assessment of therapeutic efficacy necessitates a regular
      and long-lasting surveillance of the patient. It can be provided by peak-flow
      measurement, performed by the patient himself. Finally, the close cooperation by
      patient and physician as well as the elaboration of a training program teaching
      the patient pathophysiology, symptoms and therapeutic possibilities are decisive
      for therapeutic success, i.e. the best possible restitution of pulmonary
      function.

PMID- 1357734
TI  - [Treatment of depressed patients: current trends. Combination cognitive group
      therapy with cognitive adjustment for depressed inpatients].
AB  - Depressed patients represent a major part of the inpatient population. The
      following treatment program was developed in order to respond to this problem in
      a symptom- and cost-effective way. Cognitive therapy was chosen for it's learning
      aspect and combined with pharmacotherapy. The four-week treatment program is
      implemented in an open-ended group setting, where daily therapy sessions are
      associated with various group activities. The pre- and posttreatment and six
      months follow-up results of the first 80 patients are presented.

PMID- 1357736
TI  - [Acute respiratory insufficiency caused by hyperinfestation with strongyloides.
      BALF diagnosis and favourable outcome].
AB  - Hyperinfestation with Strongyloides is a severe complication in immunodepressed
      patients. It may present with various clinical signs, notably acute respiratory
      failure. Diagnosis may be difficult, particularly when the strongyloidiasis is
      associated with septicaemia caused by Gram-negative organisms. We report a new
      case of hyperinfestation with Strongyloides in a patient treated for
      periarteritis nodosa. This case was remarkable on two scores: the diagnosis
      problem raised by the presence of intrapulmonary haemorrhages, and the favourable
      outcome of an acute and initially severe respiratory failure which had required
      assisted ventilation. The role played in the patient's cure by the doses of
      thiabendazole given and the duration of their administration is discussed.

PMID- 1357737
TI  - Chairside and laboratory procedures for soldering implant retained frameworks.

PMID- 1357738
TI  - Studies of autacoid responsiveness and endothelium dependency in human umbilical
      arteries.
AB  - The effect of serotonin, prostaglandin E2 (PGE2) and PGF2 alpha on the smooth
      muscle tension in perfused human umbilical arteries was investigated before and
      after removal of the endothelium. Denudation was performed mechanically using a
      nylon filament loop, and the efficiency of the procedure was checked by electron
      microscopy. In non-denuded vessels the autacoids elicited biphasic pressure
      responses, all starting with a vasodilatation and followed by a strong
      vasoconstriction. After denudation no dilatatory responses were evoked, whereas
      the constrictory responses appeared to be unchanged. Pre-treatment of the vessels
      with methylene blue did not affect the autacoid responses. Generally the
      perfusion pressure decreased after the de-endothelialization, in some
      preparations to levels of about 50% of the initial perfusion pressure. In about
      one-third of the preparations exposure to methylene blue led to a definite
      pressure increase. The results indicate that endothelium-derived factors are
      involved in the autacoid responses and also in the maintenance of basic vascular
      tonus in the umbilical circulation.

PMID- 1357739
TI  - Clinical aspects of gastroduodenal ulcer recurrence: an overview.
AB  - Duodenal ulcer is a disease characterized by very high rates of recurrence: up to
      80% at 1 year, 95% at 2 years. Maintenance therapy will reduce relapse rates.
      However, when therapy directed against gastric acid is stopped, the slope of the
      recurrence curve is identical whether therapy is stopped after 6 weeks, 8 weeks,
      3 months, 6 months, 1 year, or 2 years. This suggests that therapy directed
      against acid does nothing to change the natural history of ulcer disease.
      Cytoprotective therapy is equally successful as H2-blockers at healing ulcer or
      reducing relapse rates, but the time to recurrence is significantly prolonged
      after either acute or maintenance cytoprotective therapy is stopped. This
      suggests that cytoprotective therapy has a beneficial effect that does improve
      the natural history of ulcer disease. The mechanism by which maintenance therapy
      reduces ulcer relapse could be masking symptoms (analgesic), accelerated healing,
      or true prevention of ulcer recurrence. By using frequent endoscopic assessment
      combined with complex statistical evaluation (calculating traditional ulcer
      prevalence, point prevalence, and maximal ulcer prevalence), we showed that
      sucralfate cytoprotection genuinely prevents ulcer recurrence. The incidence of
      asymptomatic ulcer recurrence after sucralfate is 10% but is up to 40% after H2
      blocker therapy.

PMID- 1357740
TI  - H-2 class I Ld antigen positively selects different TCR V beta gene products in
      CD8+ and CD4+ T cells.
AB  - Expression of CD4+ or CD8+ determinants and ten different TCR V beta genes was
      analysed by two-colour flow cytometry in lymph node cells (LNC) of BALB/c and dm2
      (a BALB/c Ld loss mutant) mice. TCR V beta 14 expression of CD8+ T cells and TCR
      V beta 7 and 14 of CD4+ T Cells were significantly more frequent in BALB/c than
      in dm2 LNC, whereas no differences were observed in the frequency distribution of
      TCR V beta+ CD4-CD8- double negative LNC from BALB/c versus dm2 mice. These
      results represent the first published evidence for positive selection of
      particular TCR V beta genes by individual MHC class I molecules in non
      manipulated mice.

PMID- 1357741
TI  - Treatment of the neuroleptic-nonresponsive schizophrenic patient.
AB  - The treatment and management of neuroleptic-resistant schizophrenic patients, who
      comprise 5 to 25 percent of all patients with that diagnosis, are major problems
      for psychiatry. In addition, another large group of schizophrenic patients,
      perhaps 5 to 20 percent, are intolerant of therapeutic dosages of neuroleptic
      drugs because of extrapyramidal symptoms, including akathisia, parkinsonism, and
      tardive dyskinesia. Because about 60 percent of neuroleptic-resistant
      schizophrenic patients respond to clozapine and a large percentage of neuroleptic
      intolerant patients are able to tolerate clozapine, it should be considered the
      treatment of choice for such patients until other therapies are proven to be
      superior. A trial of clozapine alone should usually be continued for up to 6
      months before it is terminated or supplemental agents are tried. Plasma levels of
      clozapine may be useful to guide dosage. The major side effects of clozapine are
      granulocytopenia or agranulocytosis (1%-2%) and a dose-related increase in the
      incidence of generalized seizures. Psychosocial treatments such as education of
      the patient and the family about the nature of the illness, rehabilitation
      programs, social skills training, and assistance in housing are generally needed
      to obtain optimal benefit from clozapine, as with other somatic therapies. If
      clozapine is unavailable, unacceptable, or not tolerated, a variety of approaches
      may be employed to supplement typical antipsychotic drugs for patients who do not
      respond adequately to these agents alone. These include lithium;
      electroconvulsive therapy; carbamazepine or valproic acid; benzodiazepines;
      antidepressant drugs; reserpine; L-dopa and amphetamine; opioid drugs; calcium
      channel blockers; and miscellaneous other pharmacologic approaches. The evidence
      for the efficacy of these ancillary somatic therapies in treatment-resistant
      patients is relatively weak. Polypharmacy should be tried only for discrete
      periods and with clear goals. If these are not achieved, supplemental medications
      should be discontinued. Psychosurgery is not a recommended alternative at this
      time.

PMID- 1357742
TI  - Oncogenes and oncoproteins in occupational carcinogenesis.
AB  - It seems increasingly likely that an important mechanism of action of certain
      workplace carcinogens in contributing to occupational carcinogenesis may be via
      the activation of cellular oncogenes, which then cause an expression of mutated
      forms or increased amounts of their oncoprotein products. Two prototypical models
      of this mechanism may be the ras oncogene and its p21 protein and the neu
      oncogene and its p185 protein. Both are known to be activated by exposure to
      common occupational carcinogens, and both are known to occur frequently in human
      tumors, including those of occupational concern such as lung cancer. Knowledge of
      their mechanisms of action may lead to new opportunities for preventing
      occupational cancer.

PMID- 1357744
TI  - [Main coronary artery stenosis: a continuous challenge].
AB  - The pre- and postoperative course in 118 patients (104 males, mean age 62 +/-
      8.1, 14 females, 60 +/- 10.7 years) who underwent coronary artery bypass surgery
      for significant left main coronary artery disease was studied to analyze the
      current management and risk factors of this lesion. Of these patients 32%
      (38/118) remained in hospital care from the date of diagnosis (coronary
      angiography) until the operation. The mean interval between diagnosis and
      operation was 39 days (range 0-166). Twelve patients (10%) had urgent procedures
      (< or = 48 hours after angiography), 25 (21%) accelerated (< or = 2 weeks), 52
      (44%) anticipated (< or = 2 months) and 30 (25%) elective procedures (> 2
      months). There was a significant negative correlation (p < 0.001) between the
      grade of stenosis and the time interval from diagnosis to operation. The
      operation technique did not differ from the usual procedure except for the less
      frequent use of the internal mammary artery as arterial conduit. Patients with
      stable angina received an internal mammary artery graft in 65% (80/118) as
      compared to 26% (6/23) of the patients with unstable angina. This differs
      significantly from the overall rate of 95% of the patients undergoing coronary
      artery bypass surgery at our institution. The rate of perioperative myocardial
      infarction was 18% (21/118). There was no significant relation between infarction
      and angina class, severity of the stenosis and the use of internal mammary artery
      as bypass graft. The hospital mortality was 4.2% (5/118) and thus was not
      different from the overall mortality of (2.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357743
TI  - [Current molecular prognostic factors in breast carcinoma].
AB  - In breast cancer the tumor stage, axillary lymph node metastases and hormone
      receptors are well established prognostic factors. Nevertheless, additional
      prognostic factors are still desirable. Recently, attention has focussed on
      molecular markers, in particular mutated genes involved in the pathogenesis of
      breast carcinoma. The first such marker to be tested for its clinical relevance
      has been the c-erbB-2 oncogene. However, the results of the many studies
      published on this subject are controversial. Further progress can be expected
      from two different strategies. The molecular pathogenesis of breast cancer must
      be elucidated in more detail, since it is likely that breast cancer is the result
      of a progressive accumulation of many different somatic mutations in diverse
      genes such as oncogenes and tumor-suppressor genes. Rather than relying on
      retrospective analyses, the clinical relevance of new markers must be tested in
      prospective clinical trials.

PMID- 1357745
TI  - [Effects of classical neurotransmitters on the neurons of hypothalamic slices in
      young and aged rats].

PMID- 1357746
TI  - [Calcium ion, excitatory amino acid and ischemic brain damage].

PMID- 1357747
TI  - Dividing up the neocortex.

PMID- 1357748
TI  - Bench to bedside: the glutamate connection.

PMID- 1357749
TI  - Calcium channels coupled to glutamate release identified by omega-Aga-IVA.
AB  - Presynaptic calcium channels are crucial elements of neuronal excitation
      secretion coupling. In mammalian brain, they have been difficult to characterize
      because most presynaptic terminals are too small to probe with electrodes, and
      available pharmacological tools such as dihydropyridines and omega-conotoxin are
      largely ineffective. Subsecond measurements of synaptosomal glutamate release
      have now been used to assess presynaptic calcium channel activity in order to
      study the action of peptide toxins from the venom of the funnel web spider
      Agelenopsis aperta, which is known to inhibit dihydropyridine and omega-conotoxin
      resistant neuronal calcium currents. A presynaptic calcium channel important in
      glutamate release is shown to be omega-Aga-IVA sensitive and omega-conotoxin
      resistant.

PMID- 1357750
TI  - Searching for markers on the AIDS trail.

PMID- 1357753
TI  - Current developments and future directions with ifosfamide: an update.
      Proceedings of a satellite symposium of the XV Congress of the European Society
      for Medical Oncology. Copenhagen, Denmark, December 2, 1990.

PMID- 1357751
TI  - Isomerase and chaperone activity of prolyl isomerase in the folding of carbonic
      anhydrase.
AB  - Several proteins have been discovered that either catalyze slow protein-folding
      reactions or assist folding in the cell. Prolyl isomerase, which has been shown
      to accelerate rate-limiting cis-trans peptidyl-proline isomerization steps in the
      folding pathway, can also participate in the protein-folding process as a
      chaperone. This function is exerted on an early folding intermediate of carbonic
      anhydrase, which is thereby prevented from aggregating, whereas the isomerase
      activity is performed later in the folding process.

PMID- 1357752
TI  - Negative selection of precursor thymocytes before their differentiation into
      CD4+CD8+ cells.
AB  - Thymic selection of the developing T cell repertoire is thought to occur at the
      CD4+CD8+ stage of differentiation and to be determined by the specificity of the
      T cell receptors (TCRs) that CD4+CD8+ thymocytes express. However, TCR signals
      can inhibit the differentiation of precursor thymocytes into CD4+CD8+ cells,
      which suggests that selection might occur earlier than thought. Indeed, in a
      negatively selecting male thymus, CD4-CD8lo precursor thymocytes that express a
      transgenic TCR to male antigen are developmentally arrested as a consequence of
      antigen encounter and fail to become CD4+CD8+. Thus, negative selection can occur
      before the CD4+CD8+ stage of differentiation.

PMID- 1357754
TI  - Carboplatin (JM-8) update: current perspectives and future directions. September
      12-16, 1990.

PMID- 1357756
TI  - [Public policy in health: a challenge of our time].

PMID- 1357755
TI  - Current perspectives on teniposide (VM-26): an international conference.
      Proceedings. London, September 2, 1989.

PMID- 1357757
TI  - [An autopsy case of malignant rheumatoid arthritis (MRA) which was difficult to
      distinguish from polyarteritis nodosa (PN)].
AB  - We encountered a patient who was diagnosed as rheumatoid arthritis (RA) at 15
      years old and developed malignant RA (MRA) within one year. He suffered from
      mononeuritis multiplex and cutaneous infarction. Despite of treatment including
      steroid pulse therapy, neuritis progressed. Lung infiltration, pancreatitis and
      intestinal bleeding were accompanied. He died of disseminated intravascular
      coagulation on 153 days after admission. Autopsy revealed systemic rheumatoid
      vasculitis in coronary artery, pancreas, liver, small and large intestine, kidney
      and lung. These severe vasculitis occurred in young RA patient are rare case and
      it is important to consider the therapy and prognosis.

PMID- 1357758
TI  - Multiple endocrine adenopathy.
AB  - The syndromes of multiple endocrine adenopathy (MEA) have associated endocrine
      abnormalities that are similar to the clinical syndromes based in the same
      hyperfunctions of parathyroid, pancreatic islets, thyroid C-cell and chromaffin
      tissue seen in sporadic cases. The natural history, histopathology and management
      of these problems when they occur in the hereditary MEA syndromes differ in
      significant and instructive ways over the isolated disorders. These differences
      and similarities of MEA adenopathies were discussed at an international
      conference, with the suggestion that the MEA syndromes afford opportunity to
      investigate regulation and control of pathogenesis in surgical endocrinological
      syndromes.

PMID- 1357759
TI  - Langerhans cells are initiators of the immunosuppressive effect of ultraviolet B
      radiation.

PMID- 1357761
TI  - Modulation of the expression of intercellular adhesion molecule-1 (ICAM-1) in
      human keratinocytes by ultraviolet (UV) radiation.

PMID- 1357762
TI  - Dopamine supersensitivity and D1/D2 synergism are unrelated to changes in
      striatal receptor density.
AB  - Experiments were conducted to elucidate the relationships among striatal dopamine
      receptor density, behavioral manifestations of D1/D2 synergism (i.e., the
      requirement of concomitant stimulation of D1 and D2 receptors for the expression
      of stereotyped sniffing, licking and gnawing), and behavioral supersensitivity to
      dopamine agonists. The state of D1/D2 synergism was found to be independent of
      striatal D1 or D2 receptor density in rats as: (1) increasing striatal D1 and/or
      D2 receptor density (as confirmed by quantitative receptor autoradiography) by
      chronic treatment with SCH 23390 (0.5 mg/kg/day for 21 days) and/or haloperidol
      (0.5 mg/kg/day for 21 days) did not alter the normal pattern of D1/D2 synergism
      as determined by behavioral responsiveness to agonist stimulation of D1 or D2
      receptors, and (2) 5 days of reserpine treatment (1 mg/kg/day), although not
      significantly changing striatal D1 or D2 receptor density, induced a breakdown in
      D1/D2 synergism (i.e., behavior was elicited by independent stimulation of D1 or
      D2 receptors). In addition, the density of striatal D2 binding sites was not
      indicative of behavioral sensitivity to D2 agonists. Chronic haloperidol
      treatment increased behavioral sensitivity to the D2 agonist quinpirole by a
      factor of 2. When tested 96 h after bilateral 6-hydroxy-dopamine injections or
      after 5 daily reserpine injections, supersensitivity to quinpirole was at least
      double that following chronic haloperidol, without accompanying increases in
      striatal D2 density. This enhanced sensitivity to quinpirole was no greater than
      that observed in neurologically intact rats treated concomitantly with a
      maximally stimulating dose of SKF 38393. Furthermore, rats with unilateral 6
      hydroxydopamine lesions that were treated chronically with eticlopride continued
      to rotate contralateral to the lesion in response to quinpirole despite having
      hemispheric symmetry of striatal D2 receptor binding. By contrast, when rats with
      unilateral 6-hydroxydopamine lesions were given 5 daily reserpine injections,
      rotation was abolished, having been replaced by intense stereotyped sniffing,
      indicative of bilateral supersensitivity. The results support the hypothesis that
      two distinct types of dopamine supersensitivity exist: a modest one associated
      with increased D2 density, and a more profound one associated with a breakdown in
      D1/D2 synergism and independent of D2 density.

PMID- 1357760
TI  - Epidermal T lymphocytes--ontogeny, features and function.

PMID- 1357763
TI  - Somatostatin binding reduced by ammonium acetate in the rat hippocampus can be
      reversed by treatment with N-carbamyl-L-glutamate plus L-arginine.
AB  - The effects of short-term (90 min), mid-term (5 days), and long-term (15 days)
      administration of ammonium acetate (5 mmol/Kg day i.p.) on the somatostatinergic
      neurotransmitter system of the rat hippocampus have been studied. Scatchard
      analysis of the binding of 125I-Tyr11-somatostatin to hippocampal dissociated
      cells indicated that administration of ammonium acetate at the times studied were
      associated with a decrease in the number of somatostatin receptors in this brain
      area, whereas the affinity of the same receptors remained unchanged.
      Administration of ammonium acetate did not affect the levels of somatostatin-like
      immunoreactivity in the hippocampus. Treatment with N-carbamyl-L-glutamate (1
      mmol/Kg, i.p.) plus L-arginine (1 mmol/kg), which lead to the conversion of
      ammonia into urea, prevented the ammonium acetate-induced changes in somatostatin
      binding in this brain area. N-carbamyl-L-glutamate plus L-arginine alone had no
      observable effect on the somatostatinergic system. The decrease in the number of
      somatostatin receptors induced by ammonium acetate might reflect a decreased
      sensitivity of the target cells to somatostatin, a phenomenon that could
      contribute to the depressed neuronal excitability induced by ammonia in the rat
      hippocampus.

PMID- 1357764
TI  - Regional distribution of neuropeptide somatostatin gene expression in the human
      brain.
AB  - The regional distribution of mRNA coding for the neuropeptide somatostatin has
      been studied in the human brain by in situ hybridization histochemistry using 32P
      labeled oligonucleotides. We show that somatostatin mRNA-containing neurons are
      widely distributed in a number of nuclei and grey areas of the human brain,
      including neocortex, putamen, nucleus caudatus, nucleus accumbens, amygdala,
      midbrain, medulla oblongata, hippocampal formation, reticular nucleus of the
      thalamus, and posterior nucleus of the hypothalamus. No significant hybridization
      signal was observed in the substantia nigra, claustrum, globus pallidus,
      thalamus, and cerebellum. The topographic localization of neurons containing SOM
      mRNA in the human brain is in agreement with previous studies using
      immunocytochemical or radioimmunoassay techniques. These results show that in
      situ hybridization histochemistry with oligonucleotide probes can be used to map
      the distribution of neurons expressing SOM mRNA in human postmortem materials.

PMID- 1357765
TI  - Alteration of 5-HT1A receptor binding sites following chronic treatment with
      ipsapirone measured by quantitative autoradiography.
AB  - Ipsapirone, a high-affinity ligand for the 5-hydroxytryptamine1A (5-HT1A)
      receptor subtype, has been shown to be a full agonist at presynaptic serotonergic
      sites and a partial agonist at postsynaptic sites. Several recent studies have
      examined the effects of chronic treatment with ipsapirone or other structurally
      related pyrimidinylpiperazine compounds, including buspirone and gepirone, on 5
      HT1A binding sites with mixed results. Since the neural mechanism responsible for
      the anxiolytic and antidepressant properties of these compounds is currently
      uncertain, further investigation of this issue appeared warranted. [3H]8-hydroxy
      2-(di-n-propylamino)-tetralin ([3H]8-OH-DPAT), a ligand specific for the 5-HT1A
      site, has been used successfully to label these sites using both membrane binding
      assays and autoradiography. Experiments were performed to determine whether
      chronic treatment with ipsapirone would differentially affect binding to 5-HT1A
      receptors at different brain sites. Rats were treated twice daily with ipsapirone
      (10 mg/kg i.p.) for 1 day or for 1, 2, or 3 weeks. Quantitative analyses were
      done of autoradiograms of in vitro [3H]8-OH-DPAT binding to selected brain
      regions. Binding in vehicle-treated rats was highest in the hippocampus, septal
      nucleus, interpeduncular nucleus, entorhinal cortex, and dorsal raphe nucleus.
      Following 3 weeks of treatment with ipsapirone, a large decline in binding was
      measured in the dorsal raphe nucleus. This decline was not seen with ipsapirone
      treatments for shorter periods. With the 3-week treatment, there were less robust
      declines in [3H]8-OH-DPAT binding in the entorhinal cortex and interpeduncular
      nucleus. Binding in the other brain regions analyzed was unaltered.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1357766
TI  - Homo- and heterosynaptic changes in efficacy are expressed in prefrontal neurons:
      an in vitro study in the rat.

PMID- 1357767
TI  - Induction of tissue transglutaminase and apoptosis by retinoic acid in the limb
      bud.
AB  - Mesenchymal cells in the limb buds of midgestation mouse embryos suffer prominent
      cell death upon exposure to retinoic acid (RA), an event likely associated with
      the micromelic and phocomelic anomalies of the resultant fetuses. It has been
      suggested, but not yet shown, that cells die by an active process termed
      apoptosis rather than by necrotic cytolysis. In certain cell types, investigators
      have previously observed a specific and early effect of RA on transcriptional
      activation of the gene for tissue transglutaminase (tTG), an enzyme suspected to
      play a role in apoptosis. We report here a distinct but transient increase in tTG
      activity which accompanied the initiation of cell death in the mesenchymal cells
      located in the central core of RA-treated limb buds. We also ascertained
      microscopically that the cytological appearance of the affected cells was
      consistent with a characterization of the process of cell death as apoptosis.

PMID- 1357768
TI  - Beta agonists in asthma--state of the art: report on a Royal Society of Medicine
      seminar.

PMID- 1357769
TI  - Heparin, aspirin and beta-blockers in the acute myocardial infarction period.

PMID- 1357770
TI  - [Mode of action of sulfasalazine in chronic inflammatory enterocolonic diseases].
AB  - We have investigated the mode of action of the sulphasalazine in ulcerative
      colitis and Crohn's ileitis. We point out: a) the activity of sulphasalazine and
      its derivative, 5-aminosalicylic acid in prostaglandin's metabolites pathway, by
      inhibition of lipoxygenase; b) a moderate activity on the cell-mediated immunity
      by weak inhibition of natural killer activity; c) the 5-amino salicylic acid is
      effective strongly like a radical scavenger.

PMID- 1357771
TI  - Cell physiology and pharmacology of gastric acid secretion.
AB  - Our stomach produces daily a large amount of hydrochloric acid at a pH close to
      1. This secretion represents a more than one million-fold in H+ ion concentration
      as compared to blood and intracellular medium of a pH of 7.4. It is due to a
      specialized cell, the parietal cell, which contains a unique transport enzyme,
      the (H+, K+)-ATPase. The parietal cell is itself under the control of several
      endocrine and paracrine stimuli operating through appropriate receptors. The
      recent progresses achieved in the knowledge of these key elements of the acid
      secretion mechanism had led to the development of specific and potent inhibitors
      of crucial interest in the treatment of ulcer disease and reflux oesophagitis
      such as histamine H2 and (H+, K+)-ATPase antagonists.

PMID- 1357772
TI  - Glutathione metabolic enzyme activities in diabetic platelets as a function of
      glycemic control.
AB  - Type 1 diabetic subjects categorized on the basis of the glycated haemoglobin
      content of their blood (low less than 7%; medium, greater than 7% and less than
      11%; high, greater than 11%) were analyzed for total intraplatelet GSH as well as
      for the steady-state kinetic parameters (apparent KM and apparent Vmax) of some
      glutathione metabolic enzymes including glutathione reductase, glutathione
      peroxidase, gamma-glutamyltrans-peptidase and glutathione-S-transferase. This
      study indicates that intraplatelet GSH content of subjects with low glycated
      haemoglobin is approximately 2-fold higher than those with medium glycated
      haemoglobin. There was no further decrease in intraplatelet-GSH in subjects with
      high glycated-haemoglobin. The kinetic parameters of the platelet-enzymes studied
      (glutathione reductase, gamma-glutamyltranspeptidase and glutathione-S
      transferase) were essentially independent of the glycation state of the subject.
      However, the apparent KM of glutathione peroxidase was approximately 4-fold
      higher in the subjects with high glycated-haemoglobin, in comparison to low
      subjects. This decrease in affinity could possibly result from the susceptibility
      of this enzyme to non-enzymatic glucosylation as purified samples of glutathione
      peroxidase incubated in vitro with glucose showed similar increases in apparent
      KM. These results are discussed in terms of the potential contribution of
      glutathione peroxidase impairment, to the hyperaggregability of the diabetic
      platelet.

PMID- 1357773
TI  - [Affective disorders. Drug treatment and electroconvulsive therapy].
AB  - Optimal treatment of mood disorders and prevention of suicide requires biological
      and psychosocial methods, therapeutic alliance and psycho-education. In moderate
      unipolar depression an antidepressant may be sufficient, if necessary potentiated
      by another antidepressant or triiodothyronine. In moderate bipolar depression
      lithium or carbamazepine are preferred. In severe unipolar and bipolar depression
      the combination of an antidepressant and lithium (or carbamazepine) or
      electroconvulsive therapy (ECT) is indicated, in psychotic depression
      neuroleptics, too. Non-selective monoamine oxidase inhibitors (MAOIs) are the
      most potent antidepressants. Moderate acute mania and mixed state may respond to
      lithium, carbamazepine or valproate only. In severe cases a neuroleptic and
      lithium are combined, or these drugs may be combined with carbamazepine or
      valproate. Electroconvulsive therapy is preferable in acute mixed states with
      marked confusion or depression. In chronic mixed state and rapid cycling,
      withdrawal of antidepressants and neuroleptics should be tried. Most patients
      will need a combination of lithium and carbamazepine or valproate. Added to these
      drugs, antidepressants are less risky. Adding thyroxin may stabilize rapid
      cycling. The combination of lithium and an antidepressant is the most potent
      prophylaxis in unipolar disorder and bipolar disorder dominated by depression.

PMID- 1357774
TI  - [Sudden cardiac death. Significance of beta blockaders].
AB  - Sudden death accounts for about 15-20% of all natural fatalities in the
      industrially developed world. Most of the victims have a substrate of extensive
      myocardial injury caused by coronary heart disease, cardiomyopathy and
      hypertensive heart disease. In most cases, the immediate cause of death is
      triggered by ventricular tachycardia which degenerates into ventricular
      fibrillation. Changes in myocardial electrical properties may be critically
      modified by ischemia, imbalance in the autonomic nervous system, electrolytic
      disorders, and haemodynamic factors. We review the causes of sudden cardiac
      death, giving special attention to the effect of beta-adrenoceptor blockade as a
      preventive measure.

PMID- 1357775
TI  - HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2
      hours: an alternative to serological DR typing in clinical practice including
      donor-recipient matching in cadaveric transplantation.
AB  - In most PCR-based tissue typing techniques the PCR amplification is followed by a
      post-amplification specificity step. In typing by PCR amplification with sequence
      specific primers (PCR-SSP), typing specificity is part of the amplification step,
      which makes the technique almost as fast as serological tissue typing. In the
      present study primers were designed for DR "low-resolution" typing by PCR-SSP,
      i.e. identifying polymorphism corresponding to the serologically defined series
      DR1-DRw18. This resolution was achieved by performing 19 PCR reactions per
      individual, 17 for assigning DR1-DRw18 and 2 for the DRw52 and DRw53
      superspecificities. Thirty cell lines and 121 individuals were typed by the DR
      "low-resolution" PCR-SSP technique, TaqI DRB-DQA-DQB RFLP analysis and serology.
      The concordance between PCR-SSP typing and RFLP analysis was 100%. The
      reproducibility was 100% in 40 samples typed on two separate occasions. No false
      positive or false-negative typing results were obtained. All homozygous and
      heterozygous combinations of DR1-DRw18 could be distinguished. Amplification
      patterns segregated according to dominant Mendelian inheritance. DNA preparation,
      PCR amplification and post-amplification processing, including gel detection,
      documentation and interpretation, were performed in 2 hours. In conclusion, PCR
      SSP is an accurate typing technique with high sensitivity, specificity and
      reproducibility. The method is rapid and inexpensive. DR "low-resolution" typing
      by the PCR-SSP technique is ideally suited for analyzing small numbers of samples
      simultaneously and is an alternative to serological DR typing in routine clinical
      practice including donor-recipient matching in cadaveric transplantations.

PMID- 1357776
TI  - Progression of HIV-related disease is associated with HLA DQ and DR alleles
      defined by restriction fragment length polymorphisms.
AB  - A cohort of 139 hemophiliacs was typed for HLA D region genes by means of
      restriction fragment length polymorphisms (RFLPs) detected by HLA DQ and DR gene
      probes. Disease progression was studied in the 65 HIV antibody-positive patients,
      who were infected by contaminated clotting factor before 1985. Strong
      associations were found between disease progression in HIV-infected patients and
      allelic DNA fragments revealed by a DQ alpha cDNA probe. A 5.5 kb fragment was
      reduced in frequency and a 4.6 kb fragment increased in frequency (p less than
      0.005) in the faster progressing group, as measured both by development of CDC
      Category IV clinical symptoms and CD4 number less than 200 x 10(6)/l. These
      results correlate with DR types deduced from the RFLP patterns revealed by DR
      beta and DQ alpha gene probes. A decrease in DR4 and an increase in both DR5 and
      the DR3 subtype found in the A1 B8 DR3 haplotype were associated with disease
      progression (p less than 0.05).

PMID- 1357777
TI  - Strong and unique associations of HLA-DPB1 alleles with other HLA antigens in a
      Japanese population.

PMID- 1357778
TI  - PCR-RFLP is as sensitive and reliable as PCR-SSO in HLA class II genotyping.

PMID- 1357779
TI  - Improvement in HLA-DQB typing by PCR-RFLP: introduction of a constant restriction
      site in one of the primers for digestion control.
AB  - The PCR-RFLP method previously reported by Inoko is a powerful technique for HLA
      class II typing. The reliability of RFLP interpretation depends on complete
      digestion by restriction endonucleases using a modified primer with restriction
      sites as an internal digestion control. The use of restriction enzymes which
      recognize specific HLA DQB allelic variations makes HLA DQB genotyping possible.

PMID- 1357780
TI  - HLA class II alleles associated with celiac disease susceptibility in a southern
      European population.
AB  - Susceptibility to celiac disease in Northern Europe is associated with the human
      leukocyte antigens (HLA) B8, DR3 and DQ2, which exist together on an extended
      haplotype. The strong predominance of this haplotype within the Northern European
      celiac populations, together with the linkage disequilibrium which occurs between
      these loci, does not allow identification of the gene(s) primarily associated
      with disease susceptibility. Studies from Southern Europe using both serology and
      examination of restriction fragment length polymorphisms (RFLP) have demonstrated
      associations with DR3, DR7 and DQ2, suggesting that the DQ locus is primarily
      involved. We investigated 43 celiac patients and 41 healthy controls from Rome,
      Italy, using sequence-specific oligonucleotide (SSO) probes, in conjunction with
      gene amplification by the polymerase chain reaction (PCR), to determine alleles
      at the DRB, DQA1, DQB1 and DPB1 loci: 19% of celiac patients possessed the
      alleles DRB1*0301 DRB3*0101, 33% DRB1*0301 DRB3*0201 and 33% of celiac patients
      were heterozygous for DRB1*1101-1201/DRB1*0701. The strongest association with
      celiac disease susceptibility was the combination of alleles DQA1*0501 DQB1*0201
      (91% celiac patients vs. 12% controls; p = 0.000002). There was no additional
      susceptibility associated with alleles at the DPB locus. This study confirms the
      hypothesis that susceptibility is associated with a particular combination of DQ
      alleles and the ethnic variation in DR frequencies is secondary to linkage
      disequilibrium with these DQ alleles.

PMID- 1357782
TI  - Advancing the understanding of multiple chemical sensitivity. Proceedings of the
      Association of Occupational and Environmental Clinics Workshop on Multiple
      Chemical Sensitivity. Washington, DC, 20-21 September 1991.

PMID- 1357781
TI  - Renal hemodynamics in canine DOCA-salt hypertension: effect of calcium channel
      blockade.
AB  - Systemic arterial blood pressure (BP), renal blood flow (RBF), and renal vascular
      resistance (RVR) were followed for 3-4 wks during the progression of DOCA-salt
      hypertension in the conscious dog. Accompanying the gradual increase in BP was an
      increase in RBF; however, RVR was unchanged. The hypertension was totally
      reversed 5-7 days after cessation of DOCA-salt treatment, but the increase in RBF
      persisted, presumably as a result of renal hypertrophy. Renal adrenoceptor
      blockade with prazosin (6 dogs) and prazosin plus idazoxan (4 dogs) caused a
      comparable decrease in BP in the normotensive and DOCA-salt hypertensive dog;
      however, RVR was decreased only in the normotensive. Similar results were
      obtained during ganglionic blockade with hexamethonium. The i.v. infusion of
      diltiazem for 1 wk restored BP of the hypertensive dog to a normotensive level,
      and hexamethonium given i.v. had little further effect on either BP or RVR. These
      results suggest a non-neurogenically mediated mechanism of canine DOCA-salt
      hypertension that is susceptible to calcium channel blockade.

PMID- 1357783
TI  - Psychiatric treatments in multiple chemical sensitivity.
AB  - Despite the controversy and uncertainty surrounding the causes of the MCS
      syndrome, psychiatric treatments may provide some relief to MCS patients. These
      approaches may help patient and physician focus on the most important goals:
      relief of symptoms and improvement of function. Success requires that physician
      and patient establish a collaborative relationship and negotiate a treatment
      plan. Behavioral treatments are most effective at reducing disability and
      promoting a return to active life. When directed at appropriate target symptoms,
      psychopharmacologic treatments may reduce some of the most distressing symptoms
      of chemical sensitivity.

PMID- 1357784
TI  - Enzyme induction and receptor-binding affinity of steroidal 20-carboxamides in
      rat hepatoma tissue culture cells.
AB  - The steroidal 20-carboxamides [(20R)- and (20S)-21-(N-substituted amino)-11
      beta,17,20-trihydroxy-3,21-dioxo-1,4-pregnadiene] recently have been shown to
      possess anti-inflammatory activity in animal models of inflammation. These N
      substituted methyl, ethyl, n-propyl, and benzyl derivatives also exhibited
      suppressive effects on plasma corticosterone and thymus function. Generally, the
      (20R)-hydroxy-20-carboxamides were more potent than the corresponding (20S)
      epimers. In continuing investigations on the glucocorticoid effects of these
      compounds, we have studied their ability to induce tyrosine aminotransferase
      (TAT), inhibit uptake of [3H]thymidine into DNA, and complete with [3H]
      dexamethasone for binding to the hepatoma tissue culture glucocorticoid receptor.
      Results indicated that the N-substituted methyl, ethyl, and n-propyl derivatives
      were full glucocorticoid agonists in the three measurements. Receptor binding
      affinities of the N-substituted carboxamides correlated well with their ability
      to induce TAT activity and to inhibit thymocyte proliferation. Structure-activity
      relationships indicated that the larger the N-substituent, the weaker the agonist
      activity in this system, and 20R isomers exhibited higher glucocorticoid agonist
      activity than the corresponding 20S isomers. This investigation is part of our
      effort to elucidate structure-activity relationships of steroidal carboxamides
      synthesized on the basis of the antedrug concept.

PMID- 1357785
TI  - Protective effect of synaptic inhibition during cerebral ischemia in rats and
      rabbits.
AB  - BACKGROUND: Excitatory neurotransmitters appear to cause cell death during
      ischemia by inducing depolarization, influx of ions, and metabolic failure in the
      postsynaptic neuron. If this hypothesis is correct, then postsynaptic membrane
      hyperpolarization and inhibition of metabolism may be protective. Antagonists of
      the excitotoxic amino acid glutamate protect neurons in culture and in animal
      models of stroke but appear to cause unacceptable side effects in humans. We
      propose an alternative strategy of protection using agonists of the inhibitory
      neurotransmitter gamma-aminobutyric acid. METHODS: We caused multifocal cerebral
      ischemia in rats and rabbits by injecting microspheres into the carotid
      circulation. We administered saline, muscimol, or MK-801 within 5 minutes of
      stroke onset. We used a bioassay to measure outcome. In rats, we also used
      learning to assess cortical function, and we performed detailed quantitative
      brain morphometry 3 months after infarction. RESULTS: Using the bioassay, we
      found that muscimol exerted a protective effect in rats (p less than 0.01). There
      was a dose-response effect seen in muscimol-treated rabbits. Rats treated with
      muscimol or MK-801 exhibited significantly better visual-spatial learning
      compared with saline-treated subjects (p less than 0.001). Hemisphere volume
      after ischemia was comparable in all groups. CONCLUSIONS: Agonists of gamma
      aminobutyric acid and antagonists of glutamate appear to protect brain during
      ischemia. Since agonists of gamma-aminobutyric acid are known to have fewer side
      effects in humans, they may prove more useful in the clinical setting as
      neuroprotective agents.

PMID- 1357787
TI  - HIV-2 prevalence in three rural regions of Senegal: low levels and heterogeneous
      distribution.

PMID- 1357786
TI  - Endothelium-derived relaxing factor in brain blood vessels is not nitric oxide.
AB  - BACKGROUND: The endothelium-derived relaxing factor that mediates the actions of
      acetylcholine is now most frequently identified as nitric oxide. Nitric oxide is
      believed to have numerous important regulating actions in neurons, blood vessels,
      and several other biological systems. SUMMARY OF REVIEW: The literature
      concerning tissue other than cerebral blood vessels supports the conclusion that
      the endothelium-derived relaxing factor for acetylcholine is either nitric oxide
      or a compound formed from and containing nitric oxide (for example, a
      nitrosothiol). However, papers can be found indicating that this endothelium
      derived mediator is not nitric oxide. In brain blood vessels the evidence is
      strongly against the conclusion that nitric oxide is the endothelium-derived
      mediator for acetylcholine. If this mediator is formed from nitric oxide, either
      in brain vessels or in other vessels, no data are available delineating how this
      synthesis is regulated or whether and where nitric oxide leaves the nitroso
      compound to initiate dilation. Indeed, cerebrovascular data now cast doubt on the
      commonly held belief that nitrosovasodilators regulate vascular tone by giving
      off nitric oxide to vascular smooth muscle. CONCLUSIONS: In brain blood vessels
      the chemical identity of the endothelium-derived relaxing factor mediating the
      action of acetylcholine is unknown, but this relaxing factor does not appear to
      be nitric oxide. If the mediator contains nitric oxide, as is probably the case,
      the means by which it activates vascular guanylate cyclase and/or produces
      dilation is unknown. Since this relaxing factor inhibits platelet
      adhesion/aggregation in cerebral vessels as well as relaxing these vessels, the
      chemical identification of this relaxing factor and the elucidation of its mode
      of action are extremely important to our understanding and control of
      cerebrovascular phenomena in health and disease.

PMID- 1357788
TI  - Engraftment with peripheral blood stem cells collected by large-volume
      leukapheresis for patients with lymphoma.
AB  - Seven patients with refractory lymphomas underwent marrow reconstitution with
      peripheral blood stem cells (PBSCs) harvested by large-volume leukapheresis
      (LVL). PBSCs were collected from all patients more than 1 month after the last
      cycle of chemotherapy, and no patient received growth factors. The median number
      of LVL procedures performed per patient was 4.5, with a mean volume of 24.5 L of
      blood processed per procedure to obtain 7 x 10(8) mononuclear cells per kg.
      Autologous PBSCs and platelets were frozen at a controlled rate in plasma and 10
      percent dimethyl sulfoxide and stored in the vapor phase of liquid nitrogen. This
      group of patients was compared to a control group (n = 18) who received medullary
      marrow (MM) transplants for the same diagnoses under the same protocols during
      the same period. Posttransplant days to white cell engraftment (PBSC = 17, MM =
      15.5) were no different. Days to platelet independence were significantly longer
      in the LVL PBSC group (PBSC = 33, MM = 16; p < 0.05). This pattern of engraftment
      is typical of patients treated in this manner. Although Day 0 platelet counts
      (PBSC = 75.5 x 10(9)/L, MM = 85 x 10(9)/L) and total single-donor unit platelet
      use (PBSC = 8, MM = 9) were no different, Day 1 platelet counts (PBSC = 128 x
      10(9)/L, MM = 61.5 x 10(9)/L; p < 0.05) and Day 14 platelet use (PBSC = 5, MM =
      8; p < 0.05) were significantly different, because of the transfusion of
      cryopreserved autologous platelets with PBSCs on Day 0.

PMID- 1357789
TI  - Large-volume leukapheresis for peripheral blood stem cell collection in patients
      with hematologic malignancies.
AB  - Large-volume leukapheresis (LVL, 15-35 L) was performed in two groups of patients
      (n = 10) with hematologic malignancies to obtain peripheral blood stem cells for
      bone marrow rescue following high-dose chemotherapy. The target cell count was 7
      x 10(8) mononuclear cells (MNCs = lymphocytes and monocytes) per kg of body
      weight. Group A patients (n = 4) were studied on Day 1 of LVL, and components
      were collected from them as four sequential samples. Total MNCs collected
      averaged 1.29 x 10(10), total colony-forming-units granulocyte-macrophage (CFU
      GM) averaged 12.1 x 10(6), and a 1.8-fold mobilization of CFU-GM was observed (p
      < 0.05, Sample 1 vs. Sample 4). Group B patients (n = 6) were studied throughout
      the three consecutive planned days of 5-hour LVL. An average of three LVL
      procedures per patient was performed (range, 1.25-4), and an average of 27 L
      (range, 24-33) of blood per LVL was processed. The blood:ACD-A ratio was 24:1
      with 3000 units of heparin per 500 mL of ACD-A; heparin was also added to the
      collection bags. The component had an average hematocrit (Hct) of 0.02 and MNC
      content of 93 percent. The patients' pre-LVL and post-LVL average Hct varied
      significantly (before Day 1, 0.36 +/- 0.08; after Day 3, 0.28 +/- 0.06; p <
      0.05). Platelet counts also decreased, with post-Day 3 counts averaging 19
      percent of the average pre-Day 1 counts (p < 0.05). A decrease in the average MNC
      count after LVL was significant on Day 1 only (p < 0.05).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1357790
TI  - The homeobox in perspective.
AB  - The discovery of the homeobox marks the beginning of a new era in developmental
      biology in which a class of master control genes, which determine the body plan,
      have been identified. Their mechanism of action can now be studied at the
      molecular level and their occurrence seems to be much more universal than
      originally anticipated.

PMID- 1357791
TI  - The emergence of the chaperone machines.
AB  - To ensure proper polypeptide folding, oligomerization and transport, elaborate
      molecular 'chaperone machines' have evolved. These machines are usually composed
      of a major chaperone protein that binds promiscuously to nascent, unfolded,
      misfolded or aggregated polypeptides and a set of chaperone 'cohorts', whose
      function is to enhance efficiency and ensure recycling. These chaperone machines
      can function by themselves or synergistically to carry out their various tasks.

PMID- 1357792
TI  - Biochemical mechanism of light adaptation in vertebrate photoreceptors.
AB  - Vertebrate photoreceptors can adjust their sensitivity to a wide range of light
      intensities spanning several orders of magnitude, the phenomenon of which is
      called light adaptation. Electrophysiological and biochemical studies have
      revealed that calcium can serve as an intracellular transmitter of light
      adaptation under the control of cGMP metabolism. After illumination, the
      cytoplasmic calcium concentration of a photoreceptor decreases, which in turn
      strongly activates photoreceptor guanylate cyclase. This calcium-dependent effect
      is mediated by a novel calcium-binding protein (recoverin) and leads to the
      restoration of the depleted cGMP pool after illumination.

PMID- 1357793
TI  - Rapid induction of intercellular adhesion molecule-1 on monocytes and
      myelomonocytic cell lines after interferon gamma treatment.
AB  - The ICAM-1 molecule is an important adhesion factor that facilitates lymphocyte
      activation as well as the movement of lymphocytes into solid tissues. It is
      poorly expressed on circulating monocytes but higher levels have been described
      following the use of some activation factors. While previous work has emphasized
      the role of interferon gamma in inducing increased ICAM-1 expression on
      nonleukocytic cells, we have demonstrated time- and dose-dependent increases on
      human monocytes and two myelomonocytic cell lines (Rc2A & U937). The increased
      level of ICAM-1 expression on the Rc2A cells was associated with higher accessory
      cell activity as determined by an increased mitogen and allogeneic response but
      specific antibody inhibition studies indicated only a partial dependence (up to
      50%) on this molecule. Class II MHC expression and IL-1 production were not
      elevated by IFNg treatment of these cells, indicating that other factors account
      for the remainder of the incremental activity observed following this treatment.

PMID- 1357794
TI  - Inhibition of alloreactivity in vitro by monoclonal antibodies directed against
      restricted isoforms of the leukocyte-common antigen (CD45).
AB  - The leukocyte common antigen (LCA) is a protein tyrosine phosphatase and is
      identified by the CD45 cluster of monoclonal antibodies. CD45 is expressed in
      high-density on cells of hematopoietic lineage and generally is
      immunoprecipitated as 4 bands (220, 205, 190, and 180 KDa). Genetic studies have
      shown that a single gene produces additional forms of the molecule by alternate
      splicing including CD45RA (220, 205), CD45RO (180), and CD45RB (220, 205, 190).
      We have prepared a CD45RB Mab termed "MT3" that binds to a sialic acid dependent
      epitope. Since the LCA is one of the major targets of antilymphocyte globulin, we
      assessed a panel of CD45 and CD45R Mab for their ability to inhibit
      alloreactivity in vitro. MT3 (CD45RB) inhibits the allogeneic MLR and inhibits
      CD4+ T cells from expressing interleukin 2 receptors, and prevents CD4+ CD45RA- T
      cells from entering the proliferative phase of the cell cycle. Mem 93 (CD45RA)
      inhibits the generation of cytotoxic T cells. These data suggest that the CD45RB
      and CD45RA isoforms of the LCA may be appropriate targets for in vivo
      immunotherapy.

PMID- 1357796
TI  - 1st International Congress on Transplantation in Developing Countries. Singapore,
      April 29-May 3, 1992.

PMID- 1357795
TI  - Intrauterine xenotransplantation of bone marrow stem cells in nonhuman primates.

PMID- 1357798
TI  - An overview of experimental work presented at the First International Congress on
      Transplantation in Developing Countries.

PMID- 1357797
TI  - Restriction fragment length polymorphism analysis of HLA-DRB, -DQA, and -DQB
      genes in south Indians and Swedish Caucasians.

PMID- 1357799
TI  - Optimal bone marrow dose for long-term engraftment after total lymphoid
      irradiation in dogs.

PMID- 1357800
TI  - [Surgical interventions in ulcer diseases in Denmark. A questionnaire study].
AB  - Surgical practice in the treatment of peptic ulceration in Denmark is illustrated
      by means of a questionnaire. The percentage of replies was 96. The investigation
      reveals that the predominant method of elective surgery for duodenal ulceration
      is still proximal gastric vagotomy rather than vagotomy+antrectomy. In elective
      surgery for prepyloric ulcer, vagotomy+antrectomy is employed most frequently and
      for elective operation for gastric ulcer partial gastric resection. In operative
      interventions for complications of ulceration such as haemorrhage and
      perforation, the operative strategy appears to be determined by the difficult
      current possibilities for training in ulcer surgery to a not inconsiderable
      extent, rather than to be based on a rational scientific basis as the definitive
      intervention here is replaced to a great extent by minor interventions such as
      simple undersewing of a bleeding gastric ulcer followed by H2-blocker treatment
      and simple closure of a perforated duodenal ulcer.

PMID- 1357801
TI  - [Adrenergic signal transduction in heart failure].
AB  - A review over adrenergic transmembrane signalling in human heart muscle cells,
      changes in this signalling in patients with heart failure and the influence of
      medical treatment of heart failure, is presented. In heart failure, the
      myocardial contractibility is decreased, although the plasma level of
      catecholamines is elevated. This can be due to changes in the transmembrane
      signalling. In heart failure, the numbers of beta-receptors are decreased, the
      amount of Gs-protein is probably unchanged and the amount of Gi-protein is
      probably increased. Changes in signalling are described in more detail in
      patients with heart failure based on idiopathic dilated cardiomyopathy (DCM),
      where a selective down regulation of beta 1-receptors is seen. In heart failure
      of other origin, there is probably a concomitant reduction in beta 1- and beta 2
      receptors. The selective regulation in patients with DCM, can be based on
      autoantibodies. A 30% reduction in maximal response on selective beta 2
      stimulation is additionally seen in patients with DCM, probably based on an
      increase in the amount of Gi-protein. beta-antagonists increase and beta-agonists
      decrease the numbers of beta-receptors. The regulation is selective when
      selective antagonists and agonists are used, and nonselective when nonselective
      drugs are used. How other drugs affect the transmembrane signalling is still to
      be elucidated.

PMID- 1357802
TI  - [Use of anxiolytic agents in general practice during a 3-year period. A
      retrospective study from a 2-man rural practice].
AB  - In a rural general practice with two doctors and 3.671 patients and employing a
      practice data system (APEX), a retrospective review was undertaken of the
      anxiolytic drugs (ATC gr NO5B) prescribed. A total of 376 persons received 3,556
      prescriptions for a total of 121,111 DDD (Defined Daily Doses). Forty of these
      patients (approximately 10%) received half of the medicine involved and half of
      the patients received 5% of the medicine. 68% of the prescriptions were renewals
      without contact between doctor and patient. A total of 85 new users was observed
      and the number of new users/annum decreased significantly during the period. One
      hundred and fifty-two patients consumed < or = 50 DDD during the entire three
      year period (short term users) while 168 consumed > 50 DDD during one or more
      years (long term users). The long term users received anxiolytic drugs more
      frequently on account of mental illness (46%) than did the short term users
      (12%). Long term users consulted the doctor twice as frequently and were admitted
      to psychiatric departments six times as frequently during the period. One fourth
      of the long term users received disability pensions and one fourth had now or had
      previous alcohol problems.

PMID- 1357803
TI  - [Are beta 2 agonists dangerous in the treatment of asthma?].

PMID- 1357804
TI  - [Antidepressive agents to persons with senile dementia--continuously--possibly].

PMID- 1357805
TI  - [Beta 2 agonists: are they dangerous?].

PMID- 1357806
TI  - [Significance of free oxygen radicals for pathogenesis of chronic inflammatory
      disease].

PMID- 1357808
TI  - Proceedings of the 6th International Conference on Scanning Tunneling Microscopy.
      Interlaken, Switzerland, 12-16 August 1991.

PMID- 1357807
TI  - [The antimicrobial activity of non-antibiotics].

PMID- 1357809
TI  - Epidermal growth factor receptor and bladder cancer: a review.
AB  - Recently, expectations have been raised that molecular biological studies of
      human tumours may be of value in helping to predict future clinical behaviour, in
      terms of therapeutic response and long-term survival. The epidermal growth factor
      receptor (EGFr) is a cell surface receptor for EGF and transforming growth factor
      alpha which is overexpressed by a number of human tumours. This article
      principally reviews previous investigations of the role of the epidermal growth
      factor receptor in bladder cancer and examines methods of detection, the
      correlation between EGFr status and known prognostic indicators and the value of
      assessing EGFr status in predicting clinical outcome in patients with bladder
      cancer. Recent studies of the c-erbB-2 proto-oncogene in bladder cancer and of
      cell cycling using Ki-67 are included.

PMID- 1357810
TI  - Klinefelter's syndrome associated with unilateral cryptorchidism and chordee
      without hypospadia.
AB  - We report a case of Klinefelter's syndrome associated with unilateral
      cryptorchidism and chordee without hypospadia. The literature is reviewed, and
      hormonal conditions of Klinefelter's syndrome during childhood are discussed.

PMID- 1357811
TI  - [The pathogenesis of the renal syndrome in hemorrhagic fever].
AB  - Lipid peroxidation was investigated in 89 patients suffering from hemorrhagic
      fever with renal syndrome. In addition to routine tests, measurements were made
      of plasma malonic dialdehyde and acyl hydroperoxides the levels of which were
      found increased 1.3-1.4-fold and 1.5-2-fold, respectively, in the severe disease
      compared to control values. The degree of lipid peroxidation intensification and
      aggravation of the symptoms proved to agree. It is suggested that abnormal lipid
      peroxidation contributes to development of renal syndrome which in hemorrhagic
      fever may progress to acute renal failure.

PMID- 1357813
TI  - Morphology and proliferation kinetics of early tumor stages induced by
      dimethylnitrosamine in rat kidneys.
AB  - A total of 49 dimethylnitrosamine (DMN)-induced rat renal cell tumors were
      analyzed and classified cytomorphologically at an early stage of development. Of
      these, 17 were basophilic-tubular tumors, two of which showed a direct transition
      to proximal tubules of the P3-segment; 21 lesions were vacuolated and contained
      glycogen; these were defined cytomorphologically as a separate tumor type the
      histogenetic derivation of which from the collecting duct system was established
      by documentation of a direct transition. Morphological similarities point to the
      lipid-storing variant of the basophilic tumor, but a carcinoma of the ducts of
      Bellini is another possible human equivalent of this tumor type. Another seven
      lesions were clear and granular cell tumors. In two of these a direct transition
      from the collecting duct system was found, thus confirming that this only
      recently established origin of experimentally induced rat renal clear cell tumors
      also applies to lesions induced by DMN. The proliferation kinetics of DMN-induced
      lesions were studied in autoradiograms after pulse-labeling with tritiated
      thymidine. The basal proliferation of these early tumor stages displayed a marked
      proliferative advantage over the normal parenchyma. The lesions were still
      subject to physiological growth stimulation as determined by 3H-TdR-continuous
      labeling with osmotic mini-pumps following unilateral nephrectomy. However,
      compared with normal kidney parenchyma, the 3H-TdR-labeling index of the lesions
      was even higher indicating a response modification during early neoplasia.

PMID- 1357812
TI  - Proliferating cell nuclear antigen in breast lesions: correlation of c-erbB-2
      oncoprotein and EGF receptor and its clinicopathological significance in breast
      cancer.
AB  - Monoclonal anti-proliferating cell nuclear antigen (PCNA PC10), which is directed
      against a 36 kDa auxiliary protein for DNA polymerase delta specific for the S
      phase of cell cycle, was used to measure tumour cell proliferation in 4 lactating
      breasts and 98 benign and malignant breast tumours. The percentage of PCNA
      positive cells determined by point counting was significantly lower in the
      lactating breast [mean 3.6%, standard deviation (SD) 0.67, n = 5] than in
      fibroadenoma and mastopathy (mean 23.7, SD 5.0, n = 2). Primary breast carcinoma
      showed a PCNA index ranging from 2% to 36% (mean 12.3, SD 9.3, n = 50), whereas
      in recurrent carcinoma the index was mean 28.5, SD 4.0. A high index was
      correlated with c-erbB-2 and epidermal growth factor (EGF) receptor membrane
      reactivity, worsening histological grade, poor survival and disease-free
      survival. The expression of c-erbB-2 and EGF receptor was associated with poor
      survival and disease-free survival in primary breast cancer patients.

PMID- 1357814
TI  - High levels of xanthine oxidoreductase in rat endothelial, epithelial and
      connective tissue cells. A relation between localization and function?
AB  - The localization of xanthine oxidoreductase activity was investigated in unfixed
      cryostat sections of various rat tissues by an enzyme histochemical method which
      specifically demonstrates both the dehydrogenase and oxidase forms of xanthine
      oxidoreductase. High activity was found in epithelial cells from skin, vagina,
      uterus, penis, liver, oral and nasal cavities, tongue, esophagus, fore-stomach
      and small intestine. In addition activity was demonstrated in sinusoidal cells of
      liver and adrenal cortex, endothelial cells in various organs and connective
      tissue fibroblasts. Xanthine oxidoreductase produces urate which is a scavenger
      of oxygen-derived radicals. Because the enzyme is found in epithelial and
      endothelial cells which are subject to relatively high oxidant stress, it is
      postulated that in these cells xanthine oxidoreductase is involved in the
      antioxidant enzyme defense system. In addition, a possible role for the enzyme in
      proliferation and differentiation processes is discussed.

PMID- 1357815
TI  - Expression of the protein kinase p-68 recognized by the monoclonal antibody TJ4C4
      in human lung neoplasms.
AB  - P68 is a protein kinase expressed by eukaryotic cells, which is inducible by
      alpha interferon, and is believed to be an important factor in the regulation of
      viral and cellular protein synthesis. We have previously reported on a monoclonal
      antibody, TJ4C4, which is able to specifically detect p68 in formalin-fixed,
      paraffin-embedded tissue. Because of its important role in regulating cellular
      protein synthesis, we hypothesized that p68 expression would vary among lung
      neoplasms with level of differentiation and degree of biosynthetic activity. A
      total of 246 untreated primary pulmonary and pleural neoplasms were studied. The
      frequency and relative intensity of p68 expression was determined by light
      microscopic evaluation of ABC immunoperoxidase stained specimens. All categories
      of tumors studied demonstrated a spectrum of p68 expression. Expression of p68
      correlated well with degree of differentiation in squamous cell carcinomas (SQCC)
      and acinar adenocarcinomas (AAC). Papillary adenocarcinoma (PAC) and
      bronchioalveolar carcinoma (BAC) expressed low levels of p68, despite their well
      differentiated appearance. Expression of the antigen in large cell carcinoma
      (LCC) was higher than that seen in either poorly differentiated AAC or SQCC.
      Neuroendocrine tumors generally showed low levels of p68 expression with the
      intermediate variant of small cell carcinoma expressing higher levels of p68 than
      the classic "oat cell" form (SCC). Carcinoid tumors expressed higher levels of
      p68 than did atypical carcinoid tumors. Mesotheliomas showed weak expression of
      p68, limited primarily to areas of glandular differentiation in the epithelioid
      form.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357816
TI  - Establishment and characterization of a cell line of congenital primitive
      neuroectodermal tumor of soft tissue.
AB  - A new human cell line, termed Muraoka, has been established from the recurrent
      tumor of a case of congenital primitive neuroectodermal tumor (PNET) arising at
      the temporofacial region of a male infant. The microscopic findings of this cell
      line were epithelioid, and the xenografted tumor in a nude mouse consisted of the
      malignant epithelioid cells. Immunohistochemically, the cells were positive for
      neuron-specific enolase, S-100 protein, carcinoembryonic antigen, cytokeratin,
      epithelial membrane antigen, and glial fibrillary acidic protein. These findings
      were quite similar to those of the epithelioid cells in the original tumor and of
      the xenografted tumor cells. Neither chromosomal abnormalities nor N-myc
      amplification were observed. Morphological differentiation after treatment with
      N6-2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (Bt2-cAMP), all-trans
      retinoic acid (RA), prostaglandin E1 (PGE1), and 5-bromo-2'-deoxyuridine (BrdU)
      showed two different results. Bt2-cAMP and PGE1 induced neuronal differentiation
      with the extension of neurites, whereas RA and BrdU predominantly induced
      Schwannian differentiation (flat cells). In these respects, the cell line Muraoka
      seems to be useful for studying characteristics of PNET as well as for developing
      the new treatments against such tumors.

PMID- 1357817
TI  - Detection of human papillomavirus types by the polymerase chain reaction and the
      differentiation between high-risk and low-risk cervical lesions.
AB  - By means of a consensus polymerase chain reaction (PCR) method, the prevalence of
      HPV types was determined in cervical biopsies from 137 women referred to the
      gynecological outpatient clinic for colposcopy because of an abnormal cervical
      smear. The prevalence of HPV was 80.3%. There was a statistically highly
      significant rise in the prevalence of the oncogenic HPV types (16, 18, 31, 33)
      with increasing severity of cervical intraepithelial neoplasia (CIN I to III),
      indicating a role for these HPV types in the pathogenesis of cervical cancer. The
      prevalence of other HPV types decreased significantly with the severity of the
      lesion, suggesting that these HPV types play a less significant role in this
      process. These data indicate that HPV typing with PCR may be a valuable tool for
      distinguishing between high-risk and low-risk cervical lesions. Furthermore, our
      results suggest that the detection of HPV types by consensus PCR in the cervix of
      patients with an abnormal smear but without histologically detectable CIN is a
      useful tool for predicting which of these patients will eventually develop CIN.
      Finally, a relatively low percentage (3%) of HPV double infections is reported in
      this study.

PMID- 1357818
TI  - Mouse liver regeneration after carbon tetrachloride injury as test system for
      hepatic growth regulators.
AB  - A test system for growth regulators based on the time course of liver
      regeneration in male NMRI mice injected intraperitoneally (ip) with 50 nmol CCl4
      at 12 is described. Regenerative DNA synthesis (labelling index) peaked at 36 h
      after CCl4 injury, and the Colcemid-assessed mitotic rate (MR) at 42 h, i.e., 6 h
      later. This response pattern was used to assess the effects of factors in liver
      extracts that regulate or modulate hepatocyte proliferation. The effect of one,
      two, four or eight ip injections of an aqueous mouse liver extract on MR was
      tested at 48 h. A 30-70% inhibition was seen only after single injections at 12
      h, 29 h or 44 h after CCl4 treatment. A 30-80% stimulation was observed after a
      single injection of the liver extract at 0, 5 or 24 h, and after two or four
      injections. The assay system could thus detect the presence of growth modulators
      in the extract. The experiments also showed that the timing was crucial. We
      recently isolated and characterized a growth inhibitory pentapeptide from mouse
      liver extracts. Using a synthetic pentapeptide with the same structure we
      reassessed the timing for growth inhibition seen with the liver extract. The
      following test system for growth inhibitors seemed most expedient: inhibitor
      administration at 29 h to affect G1-S transition, measured as reduced DNA
      synthesis at 36 h, or inhibitor administration at 44 h to affect G2-M transition,
      measured as reduced MR at 48 h.

PMID- 1357819
TI  - Intraglomerular fibronectin in rat experimental glomerulonephritis.
AB  - To clarify the mechanisms of glomerular pericapillary fibronectin deposition in
      human membranous nephropathy and mesangial proliferative glomerulonephritis,
      intraglomerular fibronectin distribution was examined by light and electron
      microscopy using the experimental rat models of Heymann and nephrotoxic serum
      nephritis. As previously demonstrated by immunofluorescence microscopy
      (Pettersson and Colvin 1978; Ikeya et al. 1985, 1986), fibronectin was
      distributed in the mesangial areas and occasionally on percicapillary walls of
      normal glomeruli, while in nephrotoxic serum nephritis and Heymann nephritis,
      fibronectin was diffusely located along glomerular capillary walls as well as in
      the mesangium. By immunoelectron microscopy using the immunogold technique,
      fibronectin was also noted in the mesangial areas and the lamina densa of the
      glomerular basement membrane (GBM) in normal glomeruli. In nephrotoxic serum
      nephritis, fibronectin was seen around mesangial cells situated between
      endothelial cells and the GBM, suggesting that pericapillary fibronectin in
      nephrotoxic serum nephritis reflects mesangial extension. However, in Heymann
      nephritis, it was found uniformly in the lamina rara interna, lamina densa and
      lamina rara externa of the GBM, indicating no specific relation to glomerular
      cells. When sections of normal and both experimental nephritis kidneys were
      incubated with fluorescein isothiocyanate conjugated with rat plasma fibronectin,
      a linear pattern of fluorescein staining along the glomerular capillary walls was
      observed in Heymann nephritis but not in normal or nephrotoxic serum nephritic
      rats. The GBM in Heymann nephritis would thus appear to have an affinity for
      plasma fibronectin. Based on the above findings, fibronectin in the GBM of rats
      with Heymann nephritis may reasonably be concluded to originate from the plasma.

PMID- 1357820
TI  - Lateral growth and terminal differentiation during repeated epidermal
      regeneration in vitro. Age dependence and modulation by cholera toxin.
AB  - By incubating multilayered primary cultures of human epidermal keratinocytes in a
      low calcium medium, the suprabasal layers can be stripped off leaving a basal
      cell monolayer. When this monolayer is refed normal calcium medium a reproducible
      series of cell kinetic, morphological and biochemical changes take place
      resulting in the regeneration of a multilayered tissue. The stripping procedure
      seems to induce the selective proliferation of a cohort of basal cells that is
      committed to vertical migration and rapid terminal differentiation. In contrast,
      when the basal cells are allowed to regenerate in the presence of the strong
      mitogen, cholera toxin, lateral growth and continued proliferation are favoured
      at the expense of the capacity of the cells to differentiate. Repeated stripping
      of the same cultures disclosed a considerable heterogeneity in the capacity of
      the basal cells to regenerate the suprabasal layers. The number of times the
      basal cells could restore the suprabasal layers after repeated stripping varied
      from four to nine times. A negative correlation between donor age and
      regenerative capacity was observed. The experiments with repeated stripping of
      the same cultures also showed that the capacity to proliferate and to restore the
      multilayering was fully retained for at least four cycles of stripping
      regeneration, whereas the capacity to terminally differentiate was rapidly lost.
      It is suggested that the present system of regenerating epidermal tissue cultures
      may serve as an experimental model for the study of epidermal tissue homeostasis
      and cellular aging.

PMID- 1357821
TI  - In vitro differentiation of the human osteosarcoma cell lines, HOS and KHOS.
AB  - The osteogenic potential of the two human osteosarcoma cell lines HOS and KHOS; a
      cell line produced by the transformation of the HOS cells by the Kirsten murine
      sarcoma virus, was studied in vitro. HOS cells cultured more than 2 weeks formed
      nodules composed of two morphologically distinct layers, an epithelial-like
      surface cell layer and a collagen-rich inner cell layer. Alkaline phosphatase
      (ALPase) activity occurred in the plasma membrane of the surface cell layer, and
      calcified substances developing along collagen fibers were detected in the
      collagen-rich inner cell layer. The calcified substances were further examined by
      analytical electron microscopy and were shown to be hydroxyapatite crystals. In
      contrast, there was neither ALPase nor the deposition of a calcified substance in
      the KHOS cells.

PMID- 1357822
TI  - [Hemodynamic effects of nitroglycerin and trimepranol in acute myocardial
      infarct].
AB  - The authors investigated the effect of intravenous nitroglycerin and trimepranol
      on the haemodynamics of patients with acute myocardial infarction. They found
      that nitroglycerin has a favourable effect on haemodynamics as it leads to a
      reduction of the pressure in the wedged pulmonary artery and to a reduction of
      oxygen requirement of the cardiac muscle, while the changes of the minute volume
      and pulse rate are insignificant. Trimepranol leads to a rise of pressure in the
      wedged pulmonary artery, sometimes to critical values, and to a decline of the
      cardiac minute output. The authors conclude that trimepranol is suitable for a
      selected group of patients with sinus tachycardia and without signs of cardiac
      failure while the pulmonary pressure is carefully monitored. Nitroglycerin can be
      administered to the majority of patients with acute myocardial infarction. To
      ensure safe administration it is sufficient to monitor the heart rate and in
      particular the systemic pressure. It is best to administer it to patients with
      extensive myocardial infarctions with a high filling pressure of the left
      ventricle.

PMID- 1357823
TI  - 1991 report concerning recommendations of the DNA commission of the International
      Society for Forensic Haemogenetics Relating to the use of DNA Polymorphism.

PMID- 1357824
TI  - [Cases of posttraumatic hemorrhagic vasculitis].

PMID- 1357825
TI  - [Current issues in chemotherapy of infectious diseases. Munich, Federal Republic
      of Germany, May 15-16, 1992. Abstracts].

PMID- 1357826
TI  - Effect of somatostatin on adenylate cyclase activity in normal and neoplastic
      thyroid tissue.
AB  - Thyroid stimulating hormone (TSH) and other substances increase adenylate cyclase
      (AC) activity and growth of normal and neoplastic thyroid tissue. Factors that
      inhibit cAMP may provide targeted therapy to tumors dependent on cAMP for growth.
      Somatostatin has been reported to inhibit the growth of gastrinomas and carcinoid
      tumors. We therefore studied the effects of somatostatin on basal, TSH, pertussis
      toxin, and forskolin stimulated adenylate cyclase activity in normal and
      neoplastic thyroid tissue from 19 patients. Adenylate cyclase (AC) activity was
      determined by the conversion of alpha 32P-ATP to 32P-cAMP in pmoles/mg protein/30
      minutes in an 8000 x g particulate fraction rich in thyroid plasma membranes. TSH
      (300 mU/ml) and forskolin (100 mM) (a diterpine that directly stimulates the
      catalytic unit of AC) increased AC activity in normal and neoplastic thyroid
      tissue. The AC stimulation was greater in the neoplasms (p less than 0.01).
      Somatostatin (5 x 10(-6)M) decreased basal and TSH stimulated AC activity below
      basal levels in both normal and neoplastic thyroid tissue (including papillary,
      follicular, and medullary carcinomas). The inhibition of AC by somatostatin was
      greater in neoplastic tissue (p less than 0.025). Pertussis toxin (which blocks
      the inhibitory guanyl nucleotide regulatory protein) was able to partially
      reverse the effect of somatostatin. Somatostatin partially inhibited forskolin
      stimulated AC activity. Somatostatin inhibits basal and TSH stimulated AC
      activity in both normal and neoplastic human thyroid tissue, with a greater
      effect on neoplasms. These studies establish that somatostatin blocks a major
      regulator of thyroid growth and provides the rationale for the use of
      somatostatin analogs in the treatment of thyroid cancers.

PMID- 1357828
TI  - Prominent corneal nerves in patients with multiple endocrine neoplasia type 2A:
      diagnostic implications.
AB  - We examined corneal nerves of 22 patients from 10 families with multiple
      endocrine neoplasia type 2A (MEN-2A). According to the findings in slit-lamp
      biomicroscopic examination and photographic documentation, the increased
      visibility of corneal nerves were classified into 5 grades (Grade 0 = invisible
      to Grade 4 = as thick as in MEN-2B). All eyes of normal subjects, 19 of 20 eyes
      of patients with anterior keratoconus, and 11 of 12 eyes of patients with non
      hereditary medullary thyroid carcinoma (MTC) were either grade 0 or 1, and the
      remaining 2 eyes were evaluated as grade 2. Of the 44 eyes of MEN-2A patients, 5
      (11.4%) eyes were grade 0, 11 (25%) eyes were grade 1, 19 (43.2%) eyes were grade
      2, 8 (18.2%) eyes were grade 3, and 1 (2.3%) eye was grade 4. Thus, more than 60%
      of eyes of MEN-2A patients showed pathologically thickened corneal nerves of
      varying degree (grade 2 or higher). There was no definite relationship between
      the grade of corneal nerve thickening and the patient's age or presence of
      pheochromocytoma. Differences in the grade of corneal nerve thickening were
      observed among affected members belonging to the same MEN-2A family, but
      unaffected members of the family never showed prominent corneal nerves of grade 2
      or higher. Our findings suggest that MTC patients with thickened corneal nerves
      might actually be MEN-2A patients and should be carefully followed for other
      components of this syndrome.

PMID- 1357827
TI  - Pancreatic tumors in multiple endocrine neoplasia type 1: clinical presentation
      and surgical treatment.
AB  - Among 33 patients with endocrine pancreatic tumors due to multiple endocrine
      neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%)
      patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning
      lesions. At least one gross tumor was found in all patients undergoing pancreatic
      surgery, including those with negative localization studies prior to operation.
      The patients also had additional macroscopic tumors as well as numerous
      microadenomas, and the lesions frequently were positive for immunostaining with
      multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and
      somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated
      patients and stained with gastrin and somatostatin antibodies. Distal, mainly
      subtotal pancreatic resection, was performed in 18 patients, eventually combined
      with caput tumor enucleation or duodenotomy, while a few patients underwent only
      tumor enucleation or a Whipple procedure. The long-term outcome of operation was
      most favorable in patients with hyperinsulinism; only 1 patient had clinical
      recurrence. Patients with hypergastrinemia experienced only transitory lowering
      of serum gastrin values after pancreatic surgery and 47% of them had or developed
      metastases. Such tumor spread was seen in 57% of the patients with non
      functioning lesions. Nine patients died from progressive tumor disease during
      follow-up. Consistent with previous studies, we found that surgery is indicated
      in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by
      radiology. In addition, these indications should be extended to also include
      patients with only biochemical markers of disease, including elevations of
      gastrin, as these indicate the presence of gross tumors.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1357830
TI  - Clinical course and thyroid stimulating hormone (TSH) receptor antibodies during
      surgical treatment of Graves' disease.
AB  - This study assessed the results of surgical treatment for Graves' disease in our
      hospital and examined the relationship between the values of thyroid stimulating
      hormone (TSH) receptor antibodies and postoperative thyroid function. From 1983
      to 1988, subtotal thyroidectomy was performed in 313 patients with Graves'
      disease. The follow-up rate was 89.1% (278 of 313 patients). Thirteen (4.2%)
      patients required methimazole postoperatively for hyperthyroidism and 23 (7.3%)
      patients required L-thyroxine postoperatively for hypothyroidism. The
      relationship between the postoperative thyroid function and TSH receptor
      antibodies was examined. The pre-operative thyrotropin binding inhibitory
      immunoglobulin (TBII) value had no relationship to postoperative thyroid
      function. Only in the patients who were hyperthyroid postoperatively did the TBII
      value remain elevated, but the value decreased gradually in patients who were not
      hyperthyroid postoperatively. In 43 of 94 patients whose pre-operative TBII
      values were high, the postoperative TBII value normalized. The higher the
      preoperative TBII value, the longer time was required for it to normalize
      postoperatively. The postoperative thyroid stimulating antibody (TSAb) values
      were higher in patients who remained hyperthyroid than in the patients who were
      not hyperthyroid. In the patients who remained hyperthyroid postoperatively,
      there was a significant correlation between the postoperative TBII value and the
      TSAB value. In the patients who were hypothyroid postoperatively, the TSBAb
      values were negative. In patients undergoing surgical treatment of Graves'
      disease, the postoperative TBII and TSAb values were related to postoperative
      hyperthyroidism. The TSBAb value had no relationship to postoperative
      hypothyroidism.

PMID- 1357829
TI  - Clinical characteristics, treatment and survival in patients with pancreatic
      tumors causing hormonal syndromes.
AB  - Eighty-five patients with endocrine pancreatic tumors associated with clinical
      syndromes of hormone excess were retrospectively analyzed regarding
      symptomatology, means of diagnosis, and results of surgical and medical treatment
      during follow-up of 3-18 years (median 8 years). The combination of angiography
      and computed tomography was most successful in pre-operative localization of both
      primary tumors and metastases. Surgery provided long term cure in 39 of 44
      patients with benign islet cell lesions, the majority having insulinomas. Forty
      one patients had malignant tumors, which at the time of diagnosis or operation
      were associated with liver and/or regional lymph gland metastases in 56% and 24%,
      respectively. Sixteen patients with metastatic disease and/or very large tumors
      were considered inoperable, 5 patients underwent palliative resection of their
      malignant tumors, while grossly radical tumor removal was accomplished in 20
      patients. Long-term cure was achieved in 5 patients by excision of primary tumors
      and localized liver or lymph gland metastases. Half of the patients, particularly
      those with insulinoma, gastrinoma, or vipoma, showed response to streptozotocin,
      in combination with other cytostatics, for a median of 24 months or a response to
      interferon for a median of 10 months. The overall 5-year and 10-year survival
      among the patients with malignant islet cells tumors was 54% and 28%,
      respectively. Absence of liver metastases at time of operation/diagnosis, smaller
      size of the primary tumor, grossly radical tumor resection as well as response to
      medical therapy predicted the more favorable survival.

PMID- 1357831
TI  - Urodynamics in patients with pheochromocytoma: a peri-operative study of 10
      cases.
AB  - Alpha receptors have been demonstrated in the bladder neck, and urinary retention
      may be the presenting symptom in an occasional pheochromocytoma patient. This
      prompted us to define the urodynamic profile in pheochromocytoma patients. Ten
      patients were studied. Except for 2 patients, all tumors secreted norepinephrine
      either alone (n = 4) or mixed (n = 4). Urodynamic studies (uroflowmetry,
      cystometry, profilometry, response to alpha-adrenergic agents) were performed
      with Urodyn 5000 chain (DANTEC) connected to a water perfused Bohler's catheter.
      Profilometry was done according to the Brown and Wickham technique. Normal values
      were those of the International Continence Society. Alpha blocker test was done
      by intravenous injection of thymoxamine (0.5 mg/kg) and was considered as
      positive if urethral closure pressure (UCP) decrease was greater than 30% after
      10 minutes. Ten patients had a pre-operative study, omitting alpha-blocker test
      in 1 patient; 5 patients consented a postoperative study. Pre-operatively we
      could demonstrate: 1) Increased UCP in 8 of 10 patients, regardless of the
      secretory pattern; 2) Response to alpha-adrenolytic agents in 7 of 9 patients;
      and postoperatively: 3) Good correlation between a positive alpha-blocker test
      and a decrease in urethral pressure in 3 of 5 patients. Urodynamics in
      pheochromocytoma patients show a typical alpha-adrenergic pattern and may explain
      bladder dysfunction as a presenting symptom.

PMID- 1357832
TI  - Clinicopathological characteristics of duodenal microgastrinomas.
AB  - Duodenal gastrinomas do not seem to behave as malignantly as sporadic pancreatic
      gastrinomas. Statistical analysis of 49 patients with sporadic pancreatic
      gastrinoma and 21 patients with sporadic duodenal gastrinoma reported since 1980
      in Japan revealed that the incidence of hepatic metastasis was 57% in patients
      with sporadic pancreatic gastrinoma and only 9% in patients with sporadic
      duodenal gastrinoma (p less than 0.01). These findings suggest that there is an
      essential biological differences between duodenal and pancreatic gastrinoma. Five
      patients with sporadic duodenal microgastrinoma (tumor diameter less than 5mm) in
      our hospital had no hepatic metastases; however, 4 patients had lymph node
      metastases. Immunohistochemical study of 5 sporadic duodenal microgastrinomas and
      6 sporadic pancreatic gastrinomas revealed that the sporadic duodenal gastrinomas
      contained significantly fewer insulin-producing or glucagon-producing cells than
      sporadic pancreatic gastrinomas. The cellular composition of the metastatic lymph
      nodes from duodenal microgastrinomas was similar to that of the primary tumor.
      This difference in cellular composition between the duodenal microgastrinomas and
      the pancreatic gastrinomas suggests that the process of development and
      differentiation of gastrinoma cells is different.

PMID- 1357833
TI  - Findings and long-term results of parathyroid surgery in multiple endocrine
      neoplasia type 1.
AB  - Forty-two patients with primary hyperparathyroidism (HPT) of multiple endocrine
      neoplasia type 1 (MEN-1) were evaluated a mean of 8.9 years after subtotal
      parathyroid resection (SPX, n = 34) or total parathyroidectomy with
      autotransplantation to the forearm (TPX, n = 23). TPX as the primary operation
      revealed asymmetric and mainly nodular enlargement of the parathyroid glands with
      the presence of at least one normal-size gland in half of the individuals. TPX
      and SPX were accompanied by resolution of the hypercalcemia in 78% and 38% of the
      patients. Persistent and recurrent HPT occurred in 22% and 61% of the patients,
      while hypoparathyroidism requiring oral supplements occurred in 30% and 12% of
      the patients, respectively. Intact serum parathyroid hormone (PTH) in the arm of
      parathyroid autograft was high in the normocalcemic patients, somewhat lower in
      the patients with recurrent HPT, and normal to very low in the hypoparathyroid
      patients. Ratios of intact PTH between the grafted and non-grafted arms varied
      from 1 to 56.3, with average of 28.1 in the normocalcemic individuals, 8.2 in the
      patients with recurrent HPT, and 3.3 in those requiring supplements to maintain
      normocalcemia. These findings substantiate an 80% to 92% reversal of
      hypercalcemia during long-term follow-up of MEN-1 patients undergoing total
      parathyroidectomy or subtotal resection of 3-4 parathyroid glands as primary
      operative procedures and demonstrate the usefulness of intact serum PTH for
      functional evaluation of parathyroid autografts.

PMID- 1357834
TI  - The value of immunohistochemical detection of P-glycoprotein in breast cancer
      before and after induction chemotherapy.
AB  - We have studied the patterns of P-glycoprotein expression before and after 3
      cycles of induction chemotherapy (5-fluorouracil, adriamycin and
      cyclophosphamide) using immunohistochemically stained paraffin-embedded specimen
      of 28 patients with locally advanced breast cancer. The frequency of P
      glycoprotein expression in untreated breast cancer turned out to be very low:
      only one out of 28 untreated, biopsy specimen at the time of diagnosis was
      positive. The frequency of P-glycoprotein expression was markedly increased from
      9.1% before chemotherapy to 63.6% after induction chemotherapy (p = 0.006). After
      3 cycles of induction chemotherapy, 25 patients had obtained clinical response to
      chemotherapy (4, CR; 21, PR). Eleven out of 25 tumors (44%) showing clinical
      response and all three tumors (100%) with minimal response have expressed P
      glycoprotein. One out of 6 patients (16.7%) with microscopic residual tumor seen
      in mastectomy specimen expressed P-glycoprotein, whereas 13 of 22 patients
      (59.1%) with gross residual tumor showed the presence of P-glycoprotein (p =
      0.08). The frequency of intrinsic P-glycoprotein expression in untreated breast
      cancer was quite low, but approximately half of the patients do acquire P
      glycoprotein expression during the cycles of induction chemotherapy. Therefore,
      the results suggest that the immunohistochemical detection of P-glycoprotein on
      residual tumor cells after induction chemotherapy can predict acquired drug
      resistance in breast cancer.

PMID- 1357835
TI  - [Effective operations of the foot. Report of experiences after 25 years of
      administration of the orthopedic department].
AB  - Report on proven methods of operation for the typical foot diseases. Particular
      emphasis is put on the possibilities for correction of many deformities of the
      foot through Chopart-arthrodesis by corresponding wedge-removal from the root of
      the foot, as underlined by Imhauser. The Chopart-arthrodesis is especially
      suitable for treating weight-bearing complaints of mal-healed fractures of the
      calcaneum, because this procedure stabilizes the hindfoot and sets the mid- and
      forefoot plantarly. For post-operative recurrences of toe deformities, syndactily
      operations are recommended.

PMID- 1357836
TI  - Essential role of tumor necrosis factor and other cytokines in the pathogenesis
      of cerebral malaria: experimental and clinical studies.
AB  - A natural body protein is probably a major cause of the deadliest complication of
      malaria, a finding that could point toward new methods of treatment. Studies in
      an experimental model indicate that tumor necrosis factor (TNF), a protein also
      known as cachectin, is an essential element in highly fatal cerebral malaria.
      This contention is supported by the following observations. First, during the
      course of an infection by P. berghei ANKA strain, mice of a CM-susceptible strain
      express markedly elevated levels of TNF in their serum at the time that
      neurological signs are evident. Second, in contrast, either mice from
      nonsusceptible strains, susceptible strains depleted of CD4+ T lymphocytes, or
      susceptible mice inoculated with malaria organisms incapable of producing CM all
      fail to express high serum TNF activity. Third, passive immunization against
      mouse TNF significantly prolong the survival of P. berghei-infected CBA/Ca mice,
      and prevented the development of neurologic signs to an extent that was highly
      significant. Treatment with the anti-TNF antibody also prevents the
      histopathological lesions that are characteristic of CM, i.e. plugging of
      cerebral vessels by macrophages, lymphoid and parasitized erythrocytes. We have
      recently shown that this increased TNF release and macrophage accumulation are
      schematically made of two components, each mediated by different cytokines
      presumably released by stimulated CD4+ T lymphocytes: (a) a quantitative
      component: increased accumulation of macrophages results from the concomitant
      release of IL-3 and GM-CSF, and (b) a qualitative component: macrophage number
      has not only to be raised, but macrophages need to be activated by IFN-gamma.
      Thus, CM appears to be the result of a cytokine cascade mediated by the immune
      response. TNF might also be involved in the pathogenesis of human cerebral
      malaria. Indeed, we have recently shown that in african children with falciparum
      malaria, elevated serum concentrations of this molecule are associated with
      severe neurological involvement and fatal outcome. Clinical trials of treatment
      with monoclonal anti-TNF antibodies are presently underway in an attempt to
      reduce mortality and morbidity in african children with cerebral malaria.

PMID- 1357837
TI  - Unusual morphology of a virus which produces carbon dioxide sensitivity in
      mosquitoes.
AB  - A virus, named Matsu, presumed to be the etiologic agent of hereditary
      sensitivity to carbon dioxide in Culex quinquefasciatus mosquitoes, was adapted
      to growth in the C6/36 line of Aedes albopictus cells. Though it was expected
      that the mosquito virus would be a rhabdovirus like sigma, the etiologic agent of
      hereditary carbon dioxide sensitivity in Drosophila melanogaster flies, that was
      not the case. The virion of Matsu was found to be unlike any previously described
      virus. It was pleomorphic, enveloped, from 200 to 550 nm in maximum diameter, and
      contained from three to several dozen virus-like polyhedral structures
      approximately 30 nm in diameter.

PMID- 1357838
TI  - [The interaction of mediators with protein synthesis processes in the visual
      cortex neurons in the goal-directed behavior of cats].
AB  - The chemical sensitivity was studied of the neurones of cats visual cortex at
      successive stages of food-procuring instrumental behaviour, formed in conditions
      of intraventricular administration of the blocker of protein synthesis the
      cyclohexamide. Animals with cyclohexamide had a low chemical sensitivity of the
      cortical neurones to microionophoretically applied solutions of acetylcholine and
      noradrenaline. In comparison with the intact animals, in animals with
      cyclohexamide the number of neurones reacting with change of the impulse activity
      at the stages of instrumental behaviour as well as the number of areactive cells,
      did not depend on the nature of the applied neurotransmitter.

PMID- 1357840
TI  - [Behavioral assessment of neuroleptics (2)--stereotypy].
AB  - This paper describes the definition of stereotypy and the different methods
      available for measuring both the form and the invariance of stereotyped behavior.
      With respect to the use of stereotypy for screening antipsychotic drugs, commonly
      used techniques for observing dopamine agonist-induced oral stereotypy in rats
      and the relevant points to analyze in the results are discussed. Apart from the
      ways of visually analyzing stereotyped behavior, some approaches for quantifying
      the intensity of stereotypy by using automated systems are also discussed.

PMID- 1357839
TI  - [The Workshop on the Recovery of Functions after Brain Damage (London, 11-13
      April 1991)].

PMID- 1357841
TI  - [Rat brain concentrations of monoamines and their metabolites after chronic
      administration of diazepam and tandospirone].
AB  - Tandospirone has been reported as a serotonergic antianxiety drug with a
      different pharmacological mechanism from benzodiazepines. In the present study,
      the brain concentrations of monoamines and their metabolites were measured,
      comparing control rats and two groups of rats which were given tandospirone (10
      mg/kg, ip) and diazepam (5 mg/kg, ip) each for 14 days. After sacrifice, brains
      of all animals were cut and divided into three portions, i.e. the cortex (COR),
      cerebellum (CER) and subcortical structures and brain stem (SS & BS). The
      concentrations of COR and SS & BS were measured using a Neurochemicalanalyzer
      (NCA, ESA, Inc., USA) with a reverse-phase column (Neurocolumn, Niko Bioscience
      Inc.). In the COR, 3-O-MDOPA (3-O-methyldopa) increased in the tandospirone
      group. In the SS & BS, 3-O-MDOPA increased in the diazepam and tandospirone
      groups. 5HIAA (5-hydroxyindoleacetic acid), DOPAC (3,4-dihydroxyphenylacetic
      acid) and HVA (homovanillic acid) decreased in the tandospirone group.

PMID- 1357842
TI  - [In situ hybridization: a principle and method].
AB  - We describe the principle and method of in situ hybridization (ISH), detecting
      neurotransmitters or neuromodulators and their related enzyme or receptor.
      Furthermore, we overview recent research reports focused on the gene expression
      of dopamine receptors. ISH technique has been applied and is one of the most
      powerful strategies in the biological research field of psychiatry.

PMID- 1357844
TI  - [Mononuclear phagocytes and the human immunodeficiency virus].

PMID- 1357843
TI  - [The hemagglutinating properties of Pseudomonas aeruginosa strains isolated from
      patients with nonspecific lung diseases].
AB  - To detect d-mannose-sensitive (MS) pili in 31 P. aeruginosa strains isolated from
      the respiratory tract of patients with inflammatory and purulent destructive
      pulmonary diseases, the hemagglutination (HA) test was used. The isolated
      Pseudomonas under study differed in the degree of manifestation of their MS
      adhesins. Among them microorganisms with pronounced HA activity (high HA titer)
      occurred, as well as those whose HA activity was less pronounced (low HA titer).
      P. aeruginosa strains with pronounced HA activity were more frequently isolated
      from patients with purulent destructive processes in the lungs. A correlation
      between the state of the patient at the moment of bacteriological examination and
      the degree of manifestation of MS pili in the P. aeruginosa strain isolated from
      this patients was established. The value of HA titer in the presence of d-mannose
      is indicative of the presence of MS adhesins in a P. aeruginosa strain.

PMID- 1357845
TI  - [Preliminary study on RFLPs for dystrophin gene in Chinese].
AB  - We have studied the RFLPs distribution and frequency of dystrophin gene in
      Chinese by using 14 subclones of complete 14 kb cDNA for the dystrophin gene as
      hybridization probes. Allelic fragments are detected in hybridization patterns of
      Pvu II/1a, Taq I/2b-3, Taq I/5b-7, Xba I/10. Among them, the allelic fragments
      (26 kb and 3.8 kb) in Pvu II/2b-3 patterns and the allelic fragments (10 kb and
      8.4 kb) in Taq I/5b-7 patterns are the new RFLPs which have never been reported.
      From the comparison of our data with those of Caucasian and Japanese respectively
      and their statistical analysis, we can obtain the results as follows: There is
      remarkable difference (p less than 0.01) of the allelic fragment frequency in Taq
      I/2 b-3 (A1 = 3.4 kb, fre. 0.04; A2 = 3.2 kb, fre. 0.96) and Xba I/10 (A1 = 7.4
      kb, fre. 0.41; A2 = 6.7 kb, fre. 0.59) between Chinese and Caucasian. The
      frequency of the allelic fragments A2 in Taq I/8 (A1 = 6.5 kb, A2 = 5.6 kb) and
      EcoR V/9 (A1 = 11.8 kb, A2 = 10.7 kb) are high in Caucasian, but have not been
      detected in Chinese. These differences are also highly significant. But the B1B2
      allelic frequencies in Taq I/5 b-7 (B1 = 3.2 kb, B2 = 1.6 kb) are the same. There
      is no significant difference in the frequency of the allelic fragments A1A2 and
      B1B2 in Pvu II/1 a between Chinese and Japanese. Preliminary results suggest that
      there probably are high frequencies for spontaneous neutral mutations in the
      evolution process of the huge dystrophin gene (about 2,300 kb). In the meantime,
      the neutral mutation frequencies of various sectional sequences have remarkable
      differences, and that of some sectional sequences of the gene between Chinese and
      Caucasian may also have remarkable differences.

PMID- 1357846
TI  - Drugs recently released in Belgium. Epanolol--Clodronate dinatrium.

PMID- 1357847
TI  - Abnormal expression of Ki-67 antigen in hair follicle of alopecia areata.
AB  - The monoclonal antibody Ki-67 was used to determine the numbers of cycling cells
      in hair follicles both in alopecia areata and in normal scalp skin. Pronounced
      nuclear staining was limited to the area below the critical line of Auber and the
      exterior part of the outer root sheath. In alopecia areata there is reduced
      nuclear Ki-67 binding in the bulb of anagen hair follicles. These findings
      indicate that inhibition of keratinocyte proliferation might be a pathogenetic
      mechanism in alopecia areata.

PMID- 1357848
TI  - Interleukin-6 in normal skin and psoriasis.
AB  - Interleukin-6 (IL-6 or BSF-2/IFN beta 2) is a component of normal human skin. IL
      6 was immunologically detected in basal keratinocytes, endothelial cells and in a
      number of mononucleated cells and fibroblasts in normal skin and sudoriparous
      ducts. In psoriasis, intense labelling of the cytoplasm in the vicinity of
      keratinocyte membranes was detected in all epidermal layers and other skin
      appendages. The fact that this interleukin acts synergistically with respect to
      IL-1 and Tumour Necrosis Factor (TNF) strengthens the hypothesis whereby IL-6 may
      contribute via its receptor action to EGF function in modulating cell hyper
      proliferation in psoriasis.

PMID- 1357849
TI  - Expression of beta-2 integrin molecules on human keratinocytes in cytokine
      mediated skin diseases.
AB  - Integrins are cell surface molecules of importance in a wide variety of cellular
      functions, including morphogenesis, cell migration and cell matrix interactions.
      The beta-2 (B2) integrin (leukocyte integrin, CD11/CD18) subfamily comprising
      three members, each consisting of a shared beta subunit (CD18) non-covalently
      associated with unique alpha subunits (CD11a, CD11b, CD11c). In the present
      study, we have analysed the expression pattern of B2 integrins on the surface of
      human keratinocytes (HKs) in biopsies obtained from healthy volunteers, from
      positive tuberculin skin tests and from patients with acute urticaria (AU),
      lichen planus (LP), psoriasis vulgaris (PV), mycosis fungoides (MF) or purpura
      pigmentosa chronica (PPC). In biopsies obtained from positive tuberculin tests
      and from the clinically involved skin of patients with LP, PV, MF or PPC, a
      multifocally occurring, suprabasal peroxidase-positive reaction was observed on
      the membranes of the HKs when the monoclonal antibodies (MABs) Dako CD11a, Dako
      p150, 95 or Dako CD18 were used. In contrast, no specific staining of the HKs was
      observed with the same MABs in biopsies from healthy volunteers, from patients
      with AU and in the uninvolved skin specimens obtained from the other patients.
      The HKs from PV, LP, MF, PPC and AU patients and those from the healthy subjects
      failed to give a positive reaction when the MAB against CD11b (OKM1) was used.
      Our present findings provide further evidence that HKs may be actively involved
      in cell adhesion processes.

PMID- 1357850
TI  - A study of bone formation in osteoma cutis employing biochemical, histochemical
      and in situ hybridization techniques.
AB  - A female presenting multiple osteoma cutis lesions without underlying
      endocrinological disturbance was studied. Histologically, lesions revealed true
      bone formation with multiple osteoblastic cells. This was confirmed by
      demonstrating high alkaline phosphatase activity and osteonectin expression in
      osteoma cutis lesions. Interestingly, tenascin and type III procollagen were in
      close association to bony lesions, indicating that these matrix proteins may be
      somehow involved in bone formation. In situ hybridization revealed fibroblastic
      cells around bony lesions, which actively deposited type I collagen and
      osteonectin. One of the activators of bone formation, TGF beta, was also present
      in some osteoblastic cells. The results thus indicate that in osteoma cutis,
      fibroblasts have the ability to differentiate into osteoblastic cells, which have
      some properties of osteoblasts, such as high alkaline phosphatase activity and a
      high expression of osteonectin.

PMID- 1357851
TI  - Langerhans' cell distribution in drug eruption.
AB  - The number in and distribution of Langerhans' cells were studied in 11 patients
      with a maculopapular drug eruption. The Langerhans' cells (LC) were identified
      with a monoclonal antibody to OKT6 antigen, by employing an immunofluorescence
      technique. Skin biopsies were taken from lesional and non-lesional skin during
      the acute stage of the disease. LC in the lesional biopsies increased in number
      by 66% (p less than 0.001) and displayed more intense staining and more prominent
      dendrites than did LC from non-lesional skin. Control biopsies, taken from
      identical sites at least 4 weeks after the eruption disappeared, exhibited a cell
      distribution similar to the non-lesional acute stage (p = N.S.). Delivery of
      drugs via the circulation and their distribution into the skin may cause a type
      IV immune reaction due to LC activation by a drug-carrier complex.

PMID- 1357852
TI  - Effect of doxycycline on the generation of reactive oxygen species: a possible
      mechanism of action of acne therapy with doxycycline.
AB  - On the basis of a recent report that minocycline is effective in the treatment of
      acne inflammation by acting directly as an antioxidant on infiltrating
      neutrophils, we investigated whether doxycycline might also be capable of
      reducing the generation of reactive oxygen species, using human neutrophils and a
      cell-free, xanthine-xanthine oxidase system. The species investigated are
      superoxide radical anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical
      (OH.). Doxycycline significantly reduced the levels of O2-, H2O2 and OH.
      generated by both systems. Our results seem to suggest that the clinical
      effectiveness of doxycycline in the treatment of acne inflammation is due partly
      to its antioxidant effect on neutrophils.

PMID- 1357853
TI  - The skin as the possible reservoir for Candida albicans in the oculocutaneous
      candidiasis of heroin addicts.
AB  - We describe 2 patients who injected themselves with the same brown heroin a few
      days before hospitalization. The first patient presented with characteristic
      oculo-cutaneous candidiasis. Blood samples remained sterile during the so-called
      'septicemic syndrome' which represents the first phase of this syndrome and were
      positive for Candida albicans only when cutaneous nodules developed. The second
      patient was hospitalized for a stomach perforation and had no cutaneous or ocular
      candida involvement. Both patients were unusually colonized by C. albicans on
      their skin (particularly on hairy zones). These observations support the
      hypothesis that the skin may constitute the reservoir for C. albicans in oculo
      cutaneous candidiasis.

PMID- 1357854
TI  - Cutaneous cryptococcosis resembling molluscum contagiosum in a homosexual man
      with AIDS. Report of a case and review of the literature.
AB  - A 43-year-old homosexual man with the Acquired Immunodeficiency Syndrome (AIDS)
      developed cutaneous molluscum contagiosum-like lesions on face, ears, neck, hands
      and feet. He was admitted to our unit with fever, malaise and headache. Cytologic
      examination of skin brushing revealed numerous encapsulated budding yeasts,
      identified as Cryptococcus neoformans. Such a finding calls for a cytologic
      examination of skin lesions in patient with AIDS who present with fever and
      headache, in order to rule out a potentially life-threatening fungal infection.

PMID- 1357855
TI  - Follow-up of men with genital papilloma virus infection. Psychosexual aspects.
AB  - Genital papilloma virus infection (GPVI) is in many patients a longlasting,
      relapsing disease for which no effective treatment is available. This fact and
      the association between the virus and cancer puts much stress on the afflicted
      patient. Of 41 men with GPVI interviewed, 17 (40%) reported a negative effect of
      the disease on their sexual life. Most distressing was the fear of transmitting
      the disease to their partner. After 18 months, 15 (37%) of the 41 men still
      exhibited signs of GPVI. In the care of patients with GPVI, more attention needs
      to be paid to the psychosexual effects of the disease.

PMID- 1357856
TI  - Pityrosporum ovale and atopic dermatitis in children and young adults.
AB  - Children aged 0-21 years, 60 children with atopic dermatitis (AD), 40 children
      with rhinoconjunctivitis and or asthma (RA) and 40 children with no atopic
      history (HC) were studied to evaluate the relationship between skin colonisation
      with Pityrosporum ovale and the occurrence of specific IgE antibodies to P.
      ovale. The following studies were done: culture for P. ovale, measurement of IgE
      antibodies to P. ovale (skin prick test, RAST), Candida albicans, and
      Cladosporium herbarum (RAST) and IgG antibodies to P. ovale. P. ovale could be
      cultured with about the same frequency in children and young adults with AD and
      age-matched children with or without other atopic manifestations. In spite of
      similar colonisation, IgE antibodies against P. ovale occur only in atopy and
      more frequently in children with AD than in those with other types of atopic
      disease.

PMID- 1357857
TI  - Immediate and delayed hypersensitivity reactions to birch pollen in patients with
      atopic dermatitis.
AB  - We investigated immediate and delayed hypersensitivity to birch pollen in 10
      patients with atopic dermatitis (AD) who had experienced a worsening of their
      eczema during the birch pollen season. The patients were prick- and patch-tested
      and antigen-induced basophil histamine release and lymphocyte proliferation were
      measured. 9/10 birch pollen-allergic patients proved positive in the histamine
      release test and the results correlated with specific IgE levels measured by
      RAST. Birch pollen antigen induced lymphocyte proliferation in 6/10 patients, but
      a positive patch test result was obtained in only one case. Both peripheral blood
      monocytes and purified epidermal Langerhans' cells were able to present birch
      pollen antigen to T cells, although Langerhans' s cells seemed to function less
      efficiently in this respect.

PMID- 1357858
TI  - Effects of antihistamines on cutaneous reactions and influx of eosinophils after
      local injection of PAF, kallikrein, compound 48/80 and histamine in patients with
      chronic urticaria and healthy subjects.
AB  - The effects of one week's daily treatment with dexchlorpheniramine (3 + 3 mg x 2)
      and loratadine (10 mg x 2) on the cutaneous reactions to putative mediators of
      urticarial reactions were studied in healthy subjects and in patients with
      chronic urticaria. Biopsy specimens were taken from skin with delayed reactions
      and studied immunohistochemically for the presence of eosinophilic cationic
      protein (ECP). In healthy subjects both antihistamines significantly decreased
      the weal and flare induced by histamine and the histamine releaser compound
      48/80. They also reduced the flare seen after injection of PAF (platelet
      activating factor) and kallikrein. In patients with chronic urticaria the delayed
      reactions to PAF and kallikrein were larger than in healthy subjects. The
      immediate flare seen after injection of histamine, 48/80 and PAF, and the delayed
      reaction to 48/80, were significantly decreased by treatment with loratadine. No
      correlation was found between the clinical response and test reactions. In the
      group of healthy subjects, eosinophils were increased in the skin of all subjects
      after intradermal injection of 100 micrograms of PAF and in 50% after 1 microgram
      of PAF, but no eosinophils were seen after injection of 1 ng of PAF. In patients
      with chronic urticaria the eosinophils were increased at all sites where 1 ng of
      PAF had been injected and also at a limited number of sites of injection of
      histamine, 48/80, kallikrein and saline. Treatment with the antihistamines had no
      effect on the influx of eosinophils in the skin.

PMID- 1357859
TI  - Allergic granulomatosis and angiitis of Churg-Strauss. A case of high serum level
      of eosinophil cationic protein.
AB  - We report a case of allergic granulomatosis and angiitis of Churg-Strauss. The
      patient is a 40-year-old woman who satisfied the clinico-pathological triad of
      asthma, tissue and blood eosinophilia, and granulomatous vasculitis. We also
      measured serum eosinophil cationic protein (ECP) levels in this patient. In the
      active stage, the serum ECP level was higher than in healthy controls, declining
      in the remission stage, a finding suggesting that ECP is involved in the
      pathogenesis and course of Churg-Strauss disease.

PMID- 1357860
TI  - Red lunulae in severe alopecia areata.
AB  - The development of red nail lunulae has been extremely rarely described in
      alopecia areata. We observed 2 patients, a 30-year-old woman and a 61-year-old
      man, both suffering from severe alopecia areata, and having red lunulae. The
      colour changes, which developed a few weeks after the acute onset of hair loss,
      disappeared slowly, leaving horizontal fissures (Beau's lines).

PMID- 1357861
TI  - Psoriasiform acral dermatitis. Report of three cases.
AB  - The authors report 3 patients affected by psoriasiform acral dermatitis, a
      distinctive clinical entity characterized by a chronic dermatitis of the terminal
      phalanges, associated with marked shortening of the nail beds of the affected
      fingers. The skin biopsy showed in all cases the pathological features of a
      subacute spongiotic dermatitis. X-ray examination of affected fingers showed no
      bone or soft tissue changes. Differential diagnosis of psoriasiform acral
      dermatitis included psoriasis, atopic or contact dermatitis and corticosteroid
      induced distal phalangeal atrophy.

PMID- 1357862
TI  - Alcohol and smoking: risk factors for infectious eczematoid dermatitis?
AB  - Risk factors for infectious eczematoid dermatitis (IED) were analyzed in a study
      of males aged 19-50 years. The subjects were 43 IED patients and 226 controls
      with other skin diseases from the dermatological outpatient clinics of three
      University Hospitals in Finland. The patients' lifestyles were assessed by a self
      administered questionnaire pertaining to two specified periods: the period 12
      months before the onset of the skin disease and the period 12 months before the
      examination date. Recalled mean alcohol intake before the onset of the skin
      disease was 39.2 g/day for the IED patients and 17.1 g/day for the controls (p =
      0.04). The average number of cigarettes smoked daily was 17.7 for the IED
      patients and 10.4 for the control patients (p = 0.001). The IED patients
      significantly reduced their alcohol intake after the onset of the skin disease.
      In logistic regression analysis, IED associated with alcohol intake and smoking
      but not with coffee consumption, life events, age, marital status, or social
      group. The odds ratio for IED at an alcohol intake of 50 g/day as against no
      intake, was 1.7 (95% confidence interval 1.03-2.7), and the odds ratio at a
      tobacco consumption rate of 20 cigarettes/day as against no use of tobacco, was
      2.1 (1.2-3.7). We conclude that alcohol intake and smoking appear to be risk
      factors for infectious eczematoid dermatitis among males.

PMID- 1357863
TI  - Significance of tubuloreticular structures in infants with neonatal lupus
      erythematosus and their mothers with Sjogren's syndrome.
AB  - Four infants with neonatal lupus erythematosus who had annular erythema on the
      trunk and face reacted positively to tests for anti-Ro(SS-A)/La(SS-B) antibodies.
      Electron microscopic examination of vascular endothelial cells in the annular
      erythema revealed the presence of tubuloreticular structures. Once anti-Ro(SS
      A)/La(SS-B) antibodies had turned negative, these tubuloreticular structures were
      no longer evident in the vascular endothelial cells in the same area where
      annular erythema had been present. Mothers of these 4 infants reacted positively
      to anti-Ro(SS-A)/La(SS-B) antibodies, but had no sicca syndrome. A biopsy taken
      from the minor salivary gland of the lip of each mother revealed marked
      periductal mononuclear cell infiltration. Primary subclinical Sjogren's syndrome
      was confirmed. Tubuloreticular structures were also observed in the vascular
      endothelial cells in the region of the minor salivary gland. These findings
      suggest that the presence of tubuloreticular structures may be related to anti
      Ro(SS-A)/La (SS-B) antibodies.

PMID- 1357864
TI  - Topical glucocorticoids of the non-fluorinated double-ester type. Lack of
      atrophogenicity in normal skin as assessed by high-frequency ultrasound.
AB  - With the advent of non-fluorinated double esters the spectrum of topical
      dermatotherapy with glucocorticoids seems to have broadened to include safer
      congeners. To assess the atrophogenicity potential of glucocorticoids, high
      frequency ultrasound has been proposed. In a comparative trial using the DUB 20
      system, 24 healthy volunteers applied hydrocortisone aceponate, the corresponding
      vehicle, prednicarbate ointment and betamethasone-17-valerate ointment over a
      period of 6 weeks. While both hydrocortisone aceponate and prednicarbate ointment
      induced no significant reduction in skin thickness, the onset of epidermal-dermal
      thinning with betamethasone-17-valerate was early and the extent marked. These
      findings imply an increased therapeutic index with the non-fluorinated double
      esters.

PMID- 1357865
TI  - Serum levels of vitamin D metabolites in isotretinoin-treated acne patients.
AB  - Serum levels of vitamin D metabolites were determined in 11 patients treated for
      cystic acne with a four-month course of isotretinoin (Roaccutane). The levels
      were measured before treatment and after two months of medication. We found a
      significant fall in the level of 1,25-dihydroxyvitamin D (p less than 0.01) and a
      significant increase in the molar ratio of 24, 25-dihydroxyvitamin D to 25
      hydroxyvitamin D (p less than 0.05). No significant changes were found for the
      vitamin D metabolites 25-hydroxyvitamin D or 24,25-dihydroxy-vitamin D, for serum
      calcium, phosphorus, alkaline phosphatase or parathyroid hormone. Our data
      indicate early changes in the metabolism of vitamin D in patients on retinoid
      treatment.

PMID- 1357866
TI  - Delayed hypersensitivity reactions following allergic and irritant inflammation.
AB  - Delayed hypersensitivity retest reaction 3 and 6 weeks after induction of
      allergic and irritant inflammation, was studied in 13 females with known
      hypersensitivity to nickel. An increased retest reaction compared to controls was
      observed only in sites of earlier specific allergic inflammation. Also a general
      down-regulation of the degree of hypersensitivity was observed at retesting.

PMID- 1357867
TI  - Effect of drugs on the early and late phase UV erythema.
AB  - The inhibition of erythema by drugs applied topically after irradiation with 0.2
      0.8 J of 313 nm has been studied in healthy volunteers. Indomethacin and
      piroxicam markedly inhibited the erythema at 6 to 24 h after irradiation but
      erythema reappeared at 45 h. The results reported suggest that the UVB response
      is biphasic with an early phase responsive to nonsteroid anti-inflammatory drugs
      and a late phase which is not responsive. No effect on the intensity of the
      erythema was seen with betamethasone chloroquine and cetirizine. Oral intake of
      aspirin before and/or after irradiation did not influence the UV response.

PMID- 1357868
TI  - Leg and foot ulcers. Nursing care in Malmo, Sweden.
AB  - Questionnaires concerning nursing care of leg and foot ulcer patients in three
      major care-giving sectors of the national health service, namely the Department
      of Dermatology, general hospital wards/clinics, and primary care, have been
      analysed. The overall response rate was 88% (primary care: 100%). Forms regarding
      193 patients with leg ulcers and 64 patients with foot ulcers were analysed.
      Substantial differences in nursing care were noted between the three sectors. In
      55% of the leg ulcers and 45% of the foot ulcers fibrin slough was present in the
      ulcer. Black, necrotic tissue was present in 8% of the leg ulcers and 22% of the
      foot ulcers. Profuse ulcer-exudation was most commonly reported for leg ulcer
      patients treated at the Department of Dermatology, while the majority of foot
      ulcers had only a mild exudation. Frequency of dressing changes varied between
      1.4 times/week for leg ulcers at the Department of Dermatology and 9.2 times/week
      (foot ulcers 11.6) at general hospital clinics. Local wound dressings were
      exclusively chosen by physicians at the Department of Dermatology, mainly by
      physicians at general hospital clinics, and equally often by physicians and
      nurses in primary care. Time since last evaluation of the ulcer by a physician
      varied. At the general hospital clinics, 89% of the patients with leg ulcers had
      been seen by a physician within the last 2-month period. At the Department of
      Dermatology, 89% and in primary care 61% of the patients were examined within
      this period. 11% of the patients in primary care had never consulted a physician
      for their ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357869
TI  - A demographic survey of leg and foot ulcer patients in a defined population.
AB  - By means of a questionnaire sent to all medical units in Malmo, including primary
      care, homes for the elderly, and industrial health clinics, 275 patients with leg
      and foot ulcers were identified. With a population of 232,908 in Malmo, this
      corresponds to a prevalence of 0.12%, which is lower than reported by others.
      Since the response rate was high (88% total, Primary Care: 100%), the prevalence
      of 0.12% is, however, believed to be real and might be explained by the urban
      area investigated, with easy access to care and proximity to one somatic
      hospital. 50% of the patients with leg and foot ulcers were treated in Primary
      Care, and 30% of the leg ulcer patients were treated at the Department of
      Dermatology. 88% of leg and foot ulcer patients were over 75 years of age. Median
      age was 79.5 years, with 80 for women and 76.5 for men. In Primary Care the
      median age was 82. There was a predominance of women in the study population with
      an overall sex ratio of 3:1. A higher proportion of patients living alone was
      found in Primary Care. The etiology of the ulcers was considered to be "unknown"
      or "other" or else no statement was given in 36% of the leg ulcer- and 22% of the
      foot ulcer patients. This might reflect an overall uncertainty about the
      underlying etiological cause. Medially and laterally located leg ulcers were
      reported equally often, but there was also a great proportion of wholly or
      partially circumferential ulcers. 76% of the foot ulcers were located on the
      toes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357870
TI  - Effect of psoriasis heliotherapy on epidermal urocanic acid isomer
      concentrations.
AB  - A noninvasive Finn Chamber sampling method and HPLC analysis were used to
      determine epidermal urocanic acid (UCA) concentrations of psoriasis patients
      during 4 weeks of heliotherapy on the Spanish Canary Islands and a follow-up
      period of 8 weeks. During heliotherapy the epidermal cis-UCA concentration
      increased from a mean initial value of 0.2 nmol/cm2 to a mean final value of 2.9
      nmol/cm2. The total UCA concentration decreased during the first week of
      heliotherapy from an initial value of 5.5 nmol/cm2 to a nadir of 2.0 nmol/cm2.
      Thereafter, a steady increase was recorded in the total UCA level, with a maximum
      of 10.2 nmol/cm2 in week 2 of the post-treatment follow-up period. Suberythemal
      sun exposures caused near-maximal UCA isomerization, and during heliotherapy the
      cis isomer constituted 63.7-74.3% of the total UCA concentration. Clinical
      response of psoriasis to heliotherapy, however, seemed to be independent of UCA
      isomer levels.

PMID- 1357871
TI  - "Neurogenic inflammation induced by capsaicin in patients with psoriasis"--is
      really only "neuropeptides" the key word?

PMID- 1357872
TI  - Pigmented purpuric dermatosis.

PMID- 1357873
TI  - Recurrent HSV-1 virus infection complicated with recalcitrant headache treated
      with acyclovir.

PMID- 1357874
TI  - The fate of individual organisms during clearance of experimental cutaneous
      Candida albicans infections in mice.
AB  - A mouse model of acute cutaneous Candida albicans infections was used to study
      the manner in which these infections are cleared. Results of histological
      examination were correlated with determinations of the viability by acridine
      orange staining of superficial C. albicans pseudohyphae retrieved from the
      surface of the infected skin. The number of organisms retrieved from the skin
      surface was highest on the third and fourth day after inoculation, a finding
      which appeared to relate to a loss of Candida foci observed histologically to
      occur after the second day. Viability was high (approximately 80%) for at least 1
      2 days after the organisms were seen histologically to have become associated
      with neutrophils and extruded from the stratum Malpighi into the stratum corneum;
      however, at later time points (fourth and fifth day after inoculation), the
      viability of the retrieved organisms did decline. Pseudohyphae germinated in
      vitro and applied to the skin of mice were found to be non-viable when retrieved
      24 h later. These data suggest that the microbicidal processes of neutrophils may
      not be required for resolution of these infections. They are most consistent with
      clearance through an epidermal proliferative response which relocates the
      infecting organisms to a very superficial site, from which they can be either
      lost in a viable state, or subjected to killing by other factors at the skin
      surface.

PMID- 1357875
TI  - Purification of bullous pemphigoid IgG subclasses and their capability for
      complement fixation.
AB  - The antibody reactivity and complement fixing capability of circulating IgG
      subclass antibodies of patients with bullous pemphigoid (BP) were investigated.
      Four subclasses of polyclonal IgG were purified from the sera of BP patients. The
      first stage of purification was a combination of chromatographies on DEAE Affi
      Gel Blue and protein A-Cellulofine columns. The four polyclonal IgG subclasses
      were then isolated from the above-mentioned semi-purified subclass fractions
      using IgG subclass-specific immuno-affinity chromatographies. Using an
      immunohistopathological technique, IgG deposits were detected at the basement
      membrane zone (BMZ) in the normal skin incubated with IgG subclasses other than
      IgG3. C3 deposits were detected at BMZ in the skin incubated with IgG1. Neither
      IgG nor C3 deposits were in skin incubated with IgG3. These findings suggest that
      the subclasses of circulating BP antibodies are IgG1, IgG2 and IgG4, but not
      IgG3. Moreover, only the BP IgG1 subclass appears to fix complement.

PMID- 1357876
TI  - Zinc salts effects on granulocyte zinc concentration and chemotaxis in acne
      patients.
AB  - To explore the mechanism by which zinc acts on cutaneous inflammatory lesions, we
      studied granulocyte zinc levels and in vitro polymorphonuclear leukocyte
      chemotaxis in 20 acne patients before and after 2 months of zinc therapy (200
      mg/day zinc gluconate). The zinc level was assayed by flame absorption
      spectrophotometry and chemotaxis was performed by agarose assay. After 2 months
      of treatment, a significant decrease in granulocyte zinc level associated with
      inhibition of chemotaxis (r = 0.69) was observed in 16 patients. This suggests
      that zinc anti-inflammatory action is related to inhibition of polymorphonuclear
      leukocyte chemotaxis induced by a decreased granulocyte zinc level.

PMID- 1357877
TI  - A defective purine nucleotide synthesis pathway in psoriatic patients.
AB  - Purine nucleotide concentrations in skin- and blood-cells of psoriatic patients
      are abnormal: The increase in the steady state level of cGMP and the decrease in
      the cAMP concentrations are associated with an enhanced rate of cellular
      proliferation. Concomitantly we found in the present study decreased ADP and ATP
      concentrations in blood cells (p less than 0.0001). The change in nucleotide
      concentrations suggests a defective purine nucleotide synthesis pathway.
      Stimulation of the Krebs cycle with fumaric acid raises ATP (p less than 0.0001)
      and most probably cAMP levels and at the same time slows down the purine
      nucleotide synthesis through end-product inhibition. Both effects can inhibit DNA
      and protein synthesis activity, which results in inhibition of cellular
      proliferation. Fumaric acid seems therefore a useful treatment for psoriatic
      lesions if liver and kidney functions (purine nucleotide and urea cycle) are
      controlled during treatment.

PMID- 1357878
TI  - Alterations of skin microcirculatory rhythmic oscillations in different positions
      of the lower extremity.
AB  - Microcirculatory vasomotion is considered to be an important mechanism promoting
      and facilitating the transfer of blood cells through skin capillaries. Since skin
      vulnerability of the leg is closely associated with gravitational factors and
      skin micro-circulation, we investigated by a laser Doppler apparatus influence of
      postural changes on skin blood flow oscillations in lower limbs of healthy
      volunteers. Our data show a marked decrease in microcirculatory oscillation
      amplitudes at a frequency 7.6 (+/- 0.6) min-1 after lowering the leg. This could
      be reversed by the application of compressive bandage. Our study points toward a
      potentially important mechanism of microcirculatory impairment during
      orthostasis.

PMID- 1357879
TI  - Objective prick test evaluation: non-invasive techniques.
AB  - Prick test reactions are evaluated and quantified, comparing visual assessment
      with two non-invasive techniques: remittance spectroscopy and pulsed ultrasound
      for erythema and skin thickness measurements. Different information is provided
      by the two methods. Remittance spectroscopy discriminates well between negative
      and positive reactions (+ or ++), while failing to differentiate stronger
      reactions, where edema is a prominent feature. The latter reactions are better
      evaluated by skin thickness measurements, which, on the contrary, are less
      sensitive in revealing small skin thickness increases in weak reactions.

PMID- 1357881
TI  - In vitro assessment of 'T' lymphocyte functioning in vitiligo. Support for
      autoimmune hypothesis concerning the disease.
AB  - Ten patients with vitiligo in the active state of the disease and an equal number
      of age- and sex-matched controls were selected for certain immunological markers.
      A significantly high production of leukocyte migration inhibition factor was
      observed in these patients when compared with controls. Levels of immunoglobulin
      G were found to be significantly elevated. Eighty percent of the cases showed
      elevated levels of circulating immune complexes. Our investigation supports the
      autoimmune hypothesis for the disease, showing an increased release of LMIF with
      a subsequent activation of B-cells which might have led to the observed
      hypergammaglobulinaemia and elevated levels of circulating immune complexes in
      these patients.

PMID- 1357880
TI  - Skin sensitization to cinnamic alcohol: the role of skin metabolism.
AB  - Cinnamic alcohol and cinnamic aldehyde are a cause of allergic contact dermatitis
      in man and give rise to similar rates of positive reactions in routine patch
      testing. However, data from animal models indicates that the aldehyde is the
      stronger sensitizer of the two. Circumstantial evidence has pointed to the
      conversion of alcohol to aldehyde in skin as the cause of cinnamic alcohol
      sensitization. This report discusses the subject in the light of studies of skin
      metabolism of cinnamic alcohol. Evidence of limited cross reactivity between
      cinnamic alcohol and cinnamic aldehyde is supported by data showing conversion of
      cinnamic alcohol to cinnamic aldehyde by an epidermal enzyme.

PMID- 1357882
TI  - Abnormalities of lymphocyte function and phenotypic pattern in a case of toxic
      epidermal necrolysis.
AB  - We examined the blood lymphocyte function and phenotypic pattern in a patient
      with toxic epidermal necrolysis after taking salazopyrin. We studied cell surface
      markers, natural killer cell activity and mitogen-induced lymphocyte
      transformation. Our results point to temporary immunosuppression as evidenced by
      lymphopenia with a large "null cell" population, reduced natural killer cell
      activity, and impaired lymphocyte response to mitogens.

PMID- 1357883
TI  - Expression of the high affinity IgE-receptor on human Langerhans' cells.
      Elucidating the role of epidermal IgE in atopic eczema.
AB  - Epidermal Langerhans' cells have previously been shown to bear IgE molecules,
      particularly in atopic dermatitis skin. Using two highly specific antibodies
      against the antibody-binding chain of the high affinity IgE-receptor, 29C6 and
      6F7, we here provide evidence that Langerhans' cells express this receptor in
      both normal skin (foreskin) and in lesional skin of patients with atopic and
      stasis eczema. A specific antibody against the low affinity IgE-receptor, Tu1,
      showed only a low expression of this receptor. This finding has important
      potential functional implications for the role of Langerhans' cells in
      transepidermal, IgE-mediated allergy.

PMID- 1357884
TI  - Binding and uptake of Trichophyton rubrum mannan by human epidermal
      keratinocytes: a time-course study.
AB  - Trichophyton rubrum infects skin. This fungus or its products might affect the
      function of epidermal cells. We previously reported that T. rubrum mannan (TRM)
      exhibits a suppressive effect on proliferation of human lymphocytes. The goal of
      the present study was to investigate the possibility of direct interaction of TRM
      with cultured normal human epidermal keratinocytes (EK). Mannan, a cell wall
      glycoprotein, was extracted from T. rubrum by precipitation with
      cetyltrimethylammonium bromide and conjugated with fluorescein isothiocyanate
      (FITC-TRM). After incubation of EK with 50 micrograms/ml FITC-TRM for 30 min, the
      surface of EK showed bright fluorescent staining. EK cultures pretreated with non
      labelled TRM remained unstained. The fate of TRM bound to EK surface was
      determined in a time-course study. After pulse exposure to FITC-TRM, EK cultures
      were washed and incubated for various time periods. The EK moved surface mannan
      to the one area of cell membrane, so that at 4-6 h, the homogeneous staining of
      the entire cell surface was replaced by staining in a "cap" pattern. By 12 h,
      FITC-TRM was taken up into the cell, brought to the nuclear area and concentrated
      in the EK nucleoli. During the next 3 days nucleolar and cytoplasmic staining of
      the cells was observed. The intensity of fluorescence gradually diminished. On
      the 4th day, the sharp staining of organelles disappeared; instead, a large
      number of small fluorescent granules were seen intra- and extracellularly. By the
      6th day after exposure, no EK staining remained. Thus, EK specifically bound,
      internalized and apparently catabolized TRM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357885
TI  - Non-Hodgkin malignant lymphoma in the nails in the course of a chronic
      lymphocytic leukaemia.
AB  - We describe a 70-year-old woman with B-cell chronic lymphocytic leukaemia without
      nodal involvement, who developed non-Hodgkin malignant lymphoma in the toe-nails.
      Clinically, the affected nails looked like a typical mycotic infection, but later
      small tumours developed which affected the nails, and biopsy established the
      diagnosis. Treatment with chlorambucil (Leukeran) and prednisolone had a striking
      effect. Malignant infiltration of B lymphocytes in the nails is very rare, but
      should be considered in patients with malignant haematologic disease.

PMID- 1357886
TI  - Can alopecia areata be triggered by emotional stress? An uncontrolled evaluation
      of 178 patients with extensive hair loss.
AB  - One hundred and seventy-eight patients with severe alopecia areata were asked at
      interview whether they attributed their first attack of hair loss to an emotional
      trauma. Twelve patients (6.7%) reported a severely disturbing event during the 6
      months preceding the first symptoms of their disease. No patient reported that
      episodes of hair loss coincided with stressful life events. Emotional triggers
      were not especially correlated with any particular type of alopecia areata. The
      present study does not therefore provide evidence of a significant role of
      emotional stress in the pathogenesis of alopecia areata.

PMID- 1357887
TI  - The analgesic effect of EMLA cream on facial skin. Quantitative evaluation using
      argon laser stimulation.
AB  - The hypoalgesic effect of EMLA cream (Eutectic Mixture of Local Anesthetics)
      applied for 5, 15, and 30 min on facial skin was evaluated. Hypoalgesia was
      assessed by changes in pain thresholds to brief argon laser stimuli 0, 2, 5, 10,
      15, 20, 25, 30, 45, and 60 min after removal of EMLA cream. The local cutaneous
      vascular changes induced by EMLA cream was evaluated by Erythema Index determined
      by reflectance spectroscopy and by laser Doppler blood flowmetry. A large inter
      individual variability in analgesic efficacy was observed. The volunteers could
      be divided into two groups, one group of 6 persons where EMLA induced analgesia
      or considerable hypoalgesia, and one group of 4 persons where EMLA had no or only
      slight hypoalgesic effect. This great variability should be considered when EMLA
      cream is used for facial application in the clinic. Differences in local blood
      flow probably contribute to the variability. Application of EMLA cream for 5 and
      15 min did not change erythema of the skin, while 30 min of application caused
      minor blanching.

PMID- 1357888
TI  - Topical ketoconazole does not potentiate oral cyclosporin A in allergic contact
      dermatitis.
AB  - Cyclosporin A is an effective drug but its use is limited by its side effects.
      Since oral ketoconazole inhibits the metabolism of oral cyclosporin, we set out
      to find out whether topical ketoconazole would enhance the effect in the skin of
      oral cyclosporin. Five patients with contact allergic dermatitis (CAD) were given
      a 6-day course of cyclosporin (1 mg/kg/day) and applied 2% ketoconazole cream to
      an area on one arm and the inert base to the other. Serial dilutions of the
      relevant allergen were applied to the arms at 3 days for 48 hours, and the
      responses were measured objectively a day later. There was no significant
      difference between responses at the two sites, indicating that topical
      ketoconazole does not enable the dose of oral cyclosporin to be reduced in CAD.

PMID- 1357889
TI  - A new kind of skin lesion in Behcet's disease: extragenital ulcerations.
AB  - A new skin lesion was encountered in 29 of 970 Behcet's patients. The lesions
      resembled oral aphthae clinically, were recurrent and left a scar tissue like
      genital ulcers but were located extragenitally. Skin biopsies could be done in
      only 4 cases and they all showed vasculitis.

PMID- 1357890
TI  - Extraskeletal osteochondroma in the finger. Mimicking the fourth phalangeal bone.
AB  - A 36-year-old Japanese woman with an extraskeletal osteochondroma in the left
      thumb is reported. A roentgenogram showed a calcified tumor, located at the
      distal portion of the left distal phalanx, which mimicked the fourth phalangeal
      bone. The pathogenesis might in this case be hamartomatous.

PMID- 1357891
TI  - Rheumatoid arthritis: an association with pemphigus foliaceous.
AB  - We have observed a high incidence of pemphigus foliaceous, in the absence of
      therapy with penicillamine, within a small population of patients with rheumatoid
      arthritis. We suggest that penicillamine as well as inducing autoimmune disease
      might exacerbate subclinical pemphigus foliaceous in this group, accounting for
      those few patients whose skin disease fails to resolve following drug withdrawal.
      Pemphigus and rheumatoid arthritis have both been associated with HLA DR4, which
      was present in all three of our patients who were tested.

PMID- 1357892
TI  - Familial occurrence of fixed drug eruptions.
AB  - Fixed drug eruptions following the use of pyrazolone derivatives occurred in 4
      members of the same family: a 12-year-old girl, her grandmother, and two of her
      great aunts. Although the pathophysiologic events leading to this type of
      reaction are unknown, these cases of familial occurrence suggest that genetic
      predisposition might be an important causal factor.

PMID- 1357893
TI  - Acute mercury intoxication with lichenoid drug eruption followed by mercury
      contact allergy and development of antinuclear antibodies.
AB  - A 31-year-old black man was examined for evaluation of a suspected occupational
      disease. Three years earlier he had been suffering from acute mercury
      intoxication during work in a mercury recycling factory. Skin symptoms then had
      been a lichenoid drug eruption, patchy alopecia and stomatitis, which had all
      disappeared rapidly after systemic glucocorticosteroid treatment. The examination
      revealed positive patch test reactions to metallic mercury and inorganic mercury
      compounds, an elevated titre of serum antinuclear antibodies and normal IgE
      levels. The induction of antinuclear antibodies by mercury has been shown in
      animal experiments. It can be hypothesized that this patient, who may have had an
      increased individual susceptibility, became allergic to mercury by the mercury
      intoxication.

PMID- 1357894
TI  - Roxithromycin in Lyme borreliosis: discrepant results of an in vitro and in vivo
      animal susceptibility study and a clinical trial in patients with erythema
      migrans.
AB  - A new semisynthetic macrolide roxithromycin was evaluated for its potential use
      in the treatment of Lyme borreliosis. Using a macro-dilution broth technique,
      Borrelia burgdorferi was shown to be susceptible to roxithromycin with a minimal
      bactericidal concentration (MBC) of 0.06-0.25 microgram/ml. A systemic B.
      burgdorferi infection was established in gerbils; a dosage of greater than or
      equal to 25 mg/kg/day roxithromycin for 10 days eliminated the infection. A
      single blind, randomized multicenter study was performed to evaluate the efficacy
      of roxithromycin 150 mg b.i.d. versus phenoxymethyl-penicillin 1 g b.i.d. for 10
      days in patients with uncomplicated erythema migrans. The study was interrupted
      when 19 patients had enrolled because of five treatment failures. All 5 patients
      had received roxithromycin; three patients had persisting or recurrent erythema
      migrans, one developed a secondary erythema migrans-like lesion and severe
      arthralgia and one developed neuroborreliosis. B. burgdorferi was isolated from
      skin biopsies after roxithromycin therapy from two patients with persistent
      erythema migrans and both isolates were still highly susceptible to roxithromycin
      (MBC = 0.03 microgram/ml). No treatment failures were seen in 10 patients treated
      with phenoxymethyl-penicillin. Roxithromycin is thus not recommended for
      treatment of Lyme borreliosis.

PMID- 1357895
TI  - Subcorneal pustular dermatosis in a patient with Crohn's disease.
AB  - A case of subcorneal pustular dermatosis (Sneddon-Wilkinson disease) is reported
      in a patient with a one-year history of Crohn's disease. Subcorneal pustular
      dermatosis has been described in association with monoclonal gammopathy, but to
      our knowledge it has not been associated with Crohn's disease. This new
      association reinforces the hypothesis of a possible common pathogenesis for
      neutrophilic dermatoses and inflammatory bowel diseases.

PMID- 1357897
TI  - PUVA treatment of vitiligo: a retrospective study of 59 patients.
AB  - We have performed a retrospective study of 59 patients with vitiligo who received
      PUVA therapy from 1972 to 1986. Sixteen patients had generalized vitiligo and 43
      vitiligo in four locations (focal vitiligo). In both groups there were
      repigmentation in 44% of the patients. Half of the repigmented patients had
      improved more than 50%. None developed hypertrichosis, actinic keratosis,
      lentigines, or skin cancer within the observation period. Regardless of the
      results of PUVA therapy half of the patients thought PUVA was an acceptable
      therapy.

PMID- 1357896
TI  - Digital verrucous fibroangioma: a new variant of verrucous hemangioma.
AB  - In this article, we report on 4 cases of a dome-shaped nodule on the dorsum of
      the finger, which had been present since birth and slowly enlarged. On light
      microscopic examination, these nodules showed similarities to verrucous
      hemangioma. However, they were characterized by distinct clinical features and
      proliferation of dermal connective tissue. We consider these tumors to be a
      variant of verrucous hemangioma and propose to term them digital verrucous
      fibroangioma.

PMID- 1357898
TI  - Hemolytic uremic syndrome in a patient with systemic sclerosis treated with
      cyclosporin A.
AB  - The case is presented of a 48-year-old female suffering from diffuse cutaneous
      systemic sclerosis (diffuse scleroderma) since 8 years, who went into renal
      failure as part of hemolytic uremic syndrome following 3 weeks' treatment with
      3.8 mg/kg cyclosporin A. Hemolytic uremic syndrome has previously been described
      in transplant patients receiving cyclosporin A. There are also four cases
      reported in the literature of renal failure developing in middle aged females
      with diffuse cutaneous systemic sclerosis after short-term use of low dosage
      cyclosporin A treatment. It is suggested, that it may be wise not to use
      cyclosporin A to this category of patients, in which it can not be ruled out,
      that even a low dose therapy may trigger the rapid onset of scleroderma renal
      crisis or as in our case provoke hemolytic uremic syndrome.

PMID- 1357899
TI  - Escherichia coli cellulitis: two cases.
AB  - We report two cases of cellulitis of the legs occurring in adults where
      Escherichia coli (E. coli) was, or probably was, the causative bacterial agent.
      E. coli and other gram-negative bacilli cellulitis are rarely reported. However,
      in cellulitis, the causative microorganism is rarely identified, and some cases
      of E. coli cellulitis could be unrecognized. Furthermore, classical risk factors
      for gram-negative sepsis are characterized by a state of leucocyte dysfunction
      which could explain the possibility of a severe, even lethal, course of gram
      negative cellulitis. Therefore, the occurrence of cellulitis in patients with
      risk factors should prompt attempts at isolating the pathogenic microorganism,
      and a broad spectrum of antibiotic therapy should be initiated.

PMID- 1357901
TI  - HIV infection and loss of treponemal test reactivity.

PMID- 1357900
TI  - Prophylactic antibiotics for skin surgery?

PMID- 1357902
TI  - A high incidence of venereal diseases and a rapid increase of herpes zoster in
      Africa.

PMID- 1357904
TI  - Alpha-2 adrenergic agonism stimulates islet glucagon release from perfused rat
      pancreas: possible involvement of alpha-2A adrenergic receptor subtype.
AB  - Although insulin release is known to be inhibited by alpha-2 adrenergic agonism,
      the effect of alpha adrenergic agonism on islet glucagon release remains
      controversial. Alpha-2 adrenoceptors are subdivided into alpha-2A and alpha-2B
      subtypes using receptor binding methods or cloning methodology. This study was
      designed to confirm the involvement of the alpha-2 adrenoceptor and its subtypes
      in glucagon release from the isolated, perfused rat pancreas. Both the alpha-2A
      preferential agonist oxymetazoline and the non-subtype-selective alpha-2 agonist
      clonidine induced concentration-dependent stimulation of glucagon release,
      starting at 10(-8) and 10(-7) mol/l, respectively (p < 0.01). In contrast,
      neither of the two alpha-1 selective agonists, methoxamine and phenylephrine, at
      concentrations up to 10(-6) mol/l affected glucagon release. Furthermore, the non
      subtype-selective alpha-2 antagonist rauwolscine at concentrations of 10(-6) and
      10(-5) mol/l and the alpha-1 and alpha-2A selective antagonist WB-4101 at 10(-5)
      mol/l showed significant antagonism of 10(-7) mol/l clonidine-induced glucagon
      release versus corresponding controls. Neither the alpha-1 and alpha-2B selective
      antagonist prazosin nor the alpha-2B preferential antagonist chlorpromazine, at
      concentrations up to 10(-5) mol/l, antagonized the effects of clonidine. None of
      the eight drugs, at the concentrations tested, affected insulin release with 5.5
      mmol/l glucose. These results suggest that in rats islet glucagon release induced
      by alpha adrenoceptor agonism is mediated through alpha-2 adrenoceptors, possibly
      the alpha-2A subtype.

PMID- 1357903
TI  - Hormonal modulation of prolyl endopeptidase and dipeptidyl peptidase IV
      activities in the mouse uterus and ovary.
AB  - Prolyl endopeptidase and dipeptidyl peptidase IV are proline-specific peptidases,
      and are ubiquitously distributed in various tissues in mammals. The specific
      activities of these peptidases in both uterus and ovary were examined in the SHN
      strain of mice at estrus or diestrus. A marked change in prolyl endopeptidase
      activity was found in the uterus and ovary in intact mice during the estrous
      cycle, the activity being high at estrus and low at diestrus. In ovariectomized
      mice, prolyl endopeptidase activity was significantly higher in the uterus
      treated with progesterone or estradiol than in the uterus treated with vehicle
      oil only or a dopamine antagonist (perphenazine) which stimulates prolactin
      secretion. On the other hand, notable change in dipeptidyl peptidase IV activity
      during the estrous cycle was found only in the uterus of intact mice. The
      activity was low at estrus and high at diestrus. In ovariectomized mice, the
      uterus exposed to estradiol showed a lower dipeptidyl peptidase IV activity than
      the uteri treated with progesterone, the dopamine antagonist or vehicle oil.
      These findings reveal that there is a close correlation between the circulating
      level of ovarian steroids and the activities of these proline-specific enzymes.

PMID- 1357905
TI  - [Therapy of silent ischemia].
AB  - Treatment of silent ischemia is still controversial, because of the lack of
      studies showing improvement of prognosis with therapy. However, silent ischemia
      is an independent predictor of poor prognosis. Therefore significant ischemia has
      to be investigated to determine the therapeutic strategies as for patients with
      angina pectoris. The medical therapy has been reported successful with nitrates,
      beta-blockers and calcium canal blockers. The same applies for surgical therapy
      and PTCA. The target has to be to reduce myocardial ischemia and to ameliorate
      the prognosis.

PMID- 1357906
TI  - [Pathophysiology of left heart failure with reference to hemodynamic and
      neurohumoral changes].
AB  - Myocardial pump deficiency is regarded to be the hemodynamic hallmark of
      congestive heart failure. A decline of arterial pressure in the systemic
      circulation is counter-regulated by vasoconstriction in the arteriolar vascular
      bed; the compensatory vasoconstriction, however, results in an increased
      afterload that in turn aggravates myocardial pump deficiency. As part of the
      counterregulatory systems the sympathetic nervous system is activated (increase
      of neuronal activity, increased plasma norepinephrine) and the renin-angiotensin
      aldosterone system is stimulated as well (increased plasma renin activity,
      elevated angiotensin II serum levels, hyperaldosteronism). In parallel, serum
      levels of antidiuretic hormone (ADH) is despite a serum hypoosmolarity increased
      and only poorly compensated by release of the atrial natriuretic peptide. On the
      cellular level, congestive heart failure leads to a shift of the expression of
      contractile proteins towards to fetal forms (for instance myosin-isoenzymes).
      Although the counterregulatory activation of the neuroendocrine systems
      vasoconstricts the peripheral arteries thereby maintaining perfusion of vital
      organs, the rise in afterload ultimately leads to a progression of congestive
      heart failure. Consequently, vasodilators (such as ACE-inhibitors) that not only
      induce vasodilation in the peripheral arteries, but also inhibit progressive
      neuroendocrine stimulation evolved as excellent compounds for treating congestive
      heart failure.

PMID- 1357907
TI  - Clinical evaluation and pharmacological treatment of Gilles de la Tourette's
      syndrome and other hyperkinesias.
AB  - The clinical evaluation and pharmacological treatment of Gilles de la Tourette's
      syndrome (TS) and other hyperkinesias in Hvidovre Hospital is reviewed. Pimozide
      still seems to be the most effective single drug in the treatment of Tourette
      symptoms. Anticholinergics most often in combination with one or two other drugs
      are still the most effective drug in the treatment of dystonia. Clozapine is an
      effective alternative in the treatment of tremor.

PMID- 1357908
TI  - Stereology: the fast lane between neuroanatomy and brain function--or still only
      a tightrope?
AB  - Precise and unbiased quantitation of the key element of nervous tissue has solved
      some long-standing problems in neuroscience and the new stereological methods are
      now very efficient tools for experimental testing of new (and old!) ideas and
      concepts. Technically, the "zipless" combination of new stereological methods
      with certain essential principles for observation and recognition is only
      beginning to be made.

PMID- 1357909
TI  - Neurotransmitter, receptor and signal transduction disturbances in Alzheimer's
      disease.

PMID- 1357911
TI  - Alzheimer's disease. Proceedings of the Karolinska Institute 1991.

PMID- 1357910
TI  - Alzheimer's disease. Review of treatment strategies.

PMID- 1357912
TI  - Immunohistochemistry with anti-prion protein 27-30 gives reactions with fungi.

PMID- 1357914
TI  - Circulatory effects of denopamine in newborn piglets.
AB  - Denopamine is an orally active beta 1 agonist whose cardiovascular action in the
      newborn is unknown. We evaluated its circulatory effects during normoxia in
      newborn piglets less than 7 days of age. The piglets were acutely instrumented
      under general anesthesia with an electromagnetic flow probe around the main
      pulmonary artery and catheters in the main pulmonary artery, aorta, left
      ventricle, and the right and left atria. A Millar high-fidelity catheter was used
      to measure left ventricular dp/dt. The ductus arteriosus was ligated. Denopamine
      was administered in the right atrium as a continuous infusion of 2, 4, and 8
      micrograms/kg per min for 10 min each. Although cardiac index, heart rate and
      left ventricular dp/dt increased dose-dependently by 46.0 +/- 18.2%, 87.1 +/-
      34.9% and 159.9 +/- 42.4%, respectively, stroke index was not significantly
      altered. Unlike pulmonary artery pressure (which increased dose-dependently),
      aortic pressure increased with 2 and 4 micrograms/kg per min denopamine,
      respectively, it fell with 8 micrograms/kg per min denopamine. Similarly, the
      systemic vascular resistance decreased with the high dose (8 micrograms/kg per
      min). There was no significant change in pulmonary vascular resistance.
      Denopamine is potently inotropic in the adult. However, its circulatory effect in
      the neonate is dependent on its chronotropic action. Furthermore, denopamine is a
      systemic vasodilator at high doses in the neonatal circulation.

PMID- 1357913
TI  - Apraclonidine and early postoperative intraocular hypertension after cataract
      extraction.
AB  - The efficacy of topical 1% apraclonidine in controlling early postoperative IOP
      rise after cataract extraction was evaluated. Topical 1% apraclonidine was
      applied to 20 patients who underwent extracapsular cataract extraction with
      posterior intraocular lens implantation. On another 20 patients, who acted as
      control group a placebo (artificial tears) was given. The IOP was measured before
      preoperative medication and postoperatively at 6, 12 and 24 h, using the Perkins
      hand-held applanation tonometer. In the control group, 9 patients (45%) developed
      intraocular hypertension and in the treated group only 2 (10%) showed
      hypertension, but with short duration and a moderate IOP rise. The difference in
      frequency of intraocular hypertension between the groups was statistically
      significant (p less than 0.02). The statistical analysis showed that the
      postoperative IOP of operated treated eyes was significantly smaller than the IOP
      of operated control eyes. Furthermore, the postoperative IOP and the initial IOP
      did not differ statistically. The results of this study demonstrate the efficacy
      of topical apraclonidine 1% in controlling the early and transient intraocular
      hypertension following cataract extraction.

PMID- 1357915
TI  - Paranoid schizophrenics may not use irrelevant signals. The use of measures of
      blocking and of urinary dopamine.
AB  - Conditioned blocking tests for the use of superfluous (irrelevant) information in
      task-solving. Paranoid psychotic, obsessive-compulsive and healthy subjects
      usually showed normal blocking, but non-paranoid subjects tended to learn about
      the superfluous stimulus. Attenuated blocking was usually associated with
      increased dopamine utilization measured in 24h urine samples. This may reflect
      poor stabilization of response to neuroleptic medication.

PMID- 1357916
TI  - Breast carcinoma in patients receiving neuroleptic therapy. Morphologic and
      clinicopathologic features of thirteen cases.
AB  - We report 13 cases of breast carcinoma in patients treated with neuroleptics
      (prolactin-releasing drugs). Twelve of the patients were female and one was male.
      Nine patients had unicentric carcinoma, one had multicentric tumors arising
      synchronously, and three had bilateral tumors (synchronous in one case and
      metachronous in two cases). Thirteen tumors in ten patients were invasive ductal
      carcinomas, two tumors in one patient were mucinous carcinomas, and the two other
      patients had lipid-secreting carcinomas. Immunohistochemical staining showed
      alpha-lactalbumin (alpha-LA) in the lipid-secreting carcinomas at sites
      exhibiting active lipid secretion. A precise cause-effect relationship is
      difficult to elucidate, since the patients ranged in age from 40 to 64 years
      (mean: 51 years) when cancer was first diagnosed. However, the relatively high
      incidence of multiple tumors and the production of lipid and alpha-LA by the
      cancer cells were unusual features suggesting an association with neuroleptic
      therapy.

PMID- 1357918
TI  - 1st International Congress of the Polish Neuroscience Society. A Congress in the
      Decade of the Brain, Part 1. Warsaw, 21-23 September 1992. Abstracts.

PMID- 1357917
TI  - A case of adult T-cell leukemia/lymphoma, histologically presenting CD30-positive
      large cell lymphoma.
AB  - A 48-year-old Japanese woman with adult T-cell leukemia/lymphoma (ATLL),
      histologically presenting CD30-positive large cell lymphoma is reported. The
      patient, who was from an ATLL endemic area in Japan, had cutaneous nodules in the
      head, trunk, and extremities, and cervical lymph node swelling; these had been
      found three months before her admission to our hospital. A biopsy specimen of a
      skin lesion showed diffuse large cell lymphoma; the lymphoma cells were
      positively stained with CD30 (Ki-1/Ber H-2), CD4 (helper-T), and CD25
      (interleukin-2 receptor) antibodies. Anti HTLV-1 antibody (ATLA) was detected in
      the serum, and molecular cytogenetic studies of lymphoma cells showed both
      positive T-cell receptor rearrangement and HTLV-1 specific DNA sequences.

PMID- 1357919
TI  - Loss of constitutional heterozygosity in human astrocytomas.
AB  - Inactivation of tumour suppressor genes or anti-oncogenes as well as activation
      of dominant acting oncogenes seem to be important mechanisms in the pathogenesis
      of gliomas. We compared constitutional and tumoural genotypes at different
      restriction fragment length polymorphism loci (RFLP) on chromosomes 10 and 17 in
      15 unrelated individuals. Loss of heterozygosity (LOH) pointing to chromosomal
      loss or deletions was detected for at least one chromosome 17 marker in 11
      gliomas (astrocytomas grades I-III and glioblastoma multiforme), whereas LOH for
      chromosome 10 loci was only detected in 3 out of 9 cases of glioblastoma
      multiforme and was not detected in low grade gliomas. Since LOH for chromosome 10
      loci seems to be restricted only to glioblastoma multiforme, it is possible that
      recessive mutations on chromosome 10 are engaged in tumour progression from
      astrocytomas to glioblastoma multiforme. As LOH of chromosome 17 markers occurs
      in astrocytomas as in glioblastoma multiforme, chromosome 17 loci probably are
      involved in early tumour development.

PMID- 1357921
TI  - Proceedings of the International Conference on Recent Advances in
      Neurotraumatology. Porto, Portugal, November 1990.

PMID- 1357920
TI  - Proliferating cell nuclear antigen (PCNA) immunostaining as an alternative to
      bromodeoxyuridine (BrdU) immunostaining for brain tumours in paraffin embedded
      sections.
AB  - Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and
      BrdU using anti-PCNA and anti-BrdU monoclonal antibodies, respectively, was
      performed in 16 human brain tumours, including 3 glioblastomas multiforme, 2
      anaplastic astrocytomas, 1 cerebellar astrocytoma, 2 recurrent meningiomas, 4 non
      recurrent meningiomas, 3 neurinomas and 1 medulloblastoma. Patients with brain
      tumours received an injection of bromodeoxyuridine (BrdU) intravenously during
      surgery, and tumour specimens were fixed in 70% ethanol and embedded in paraffin.
      The percentage of positive cells for PCNA was compared with a BrdU labelling
      index using adjacent paraffin-embedded sections. The percentage of PCNA-positive
      cells was correlated with the BrdU labelling index and the histological
      malignancy of the brain tumours. The correlation coefficient was 0.84. This
      suggests that the immunohistochemical staining for PCNA in paraffin sections is a
      good alternative to the BrdU labelling index.

PMID- 1357922
TI  - Prevention of post-traumatic excitotoxic brain damage with NMDA antagonist drugs:
      a new strategy for the nineties.
AB  - Excitotoxic mechanisms due to overactivity of the amino acid neurotransmitters
      glutamate and aspartate maybe responsible for brain damage after injury. In this
      review we examine ischaemia and shear injury, which are relevant to human head
      injury. The opportunities for treatment using glutamate antagonist drugs are
      discussed.

PMID- 1357923
TI  - C-fos expression during electroacupuncture analgesia in rats--an
      immunohistochemical study.
AB  - Although the central mechanisms of electroacupuncture analgesia (EAA) have been
      investigated, a systematic study for the involvement of neuronal populations of
      central nervous system (CNS) in EAA has not been well undertaken, largely due to
      the difficulty in tracing the neuronal pathways by traditional techniques.
      Recently developed c-fos expression examination by immunohistochemical method
      with Ab-1 antisera might be used for this purpose as a useful marker for neuronal
      activity in CNS. In this study, tail flick latency (TFL) was tested as an index
      of pain threshold in conscious rats. After unilateral electroacupuncture was
      applied at 'Zuan-san-li' and 'Huan-tiao', the TFL was significantly prolonged. To
      explore the possible involvement of certain neuronal groups of central nervous
      system in EAA, we examined the EAA accompanied c-fos expression throughout the
      neuraxis, and a lot of specific c-fos protein labelled neurons were found in
      lumbar spinal cord (laminae I and II), nucleus raphe magnus, nucleus raphe
      dorsalis, substantia grisea centralis, nucleus habenulae lateralis, nucleus
      habenulae medialis, nucleus medialis thalami, nucleus lateralis hypothalami,
      nucleus supramamillaris, nucleus supraopticus, nucleus arcuatus, nucleus
      preopticus medialis, nucleus amygdala, nucleus tractus diagonalis, etc. No
      obvious c-fos expression was shown in these areas on control rats. These results
      strongly suggested that the functional activation of above-mentioned nuclei by
      electroacupuncture was underlied in EAA action.

PMID- 1357924
TI  - Improvement of motor function in multiple sclerosis by use of protopam chloride.
AB  - PAM, a cholinesterase reactivator, was administered orally and parenterally to 37
      patients with multiple sclerosis and a control group of 24 patients with other
      neurological diseases and pain syndromes. The effects of the administration of
      this compound in these patients with and without electrical stimulation of the
      spinal cord were studied. The clinical response to the drug follows a known time
      course and is dose related. Administration of large doses orally or intravenously
      aggravates existing neurological dysfunction. With a dose of 1,000 mg
      intravenously, a characteristic response is the temporary appearance of new
      ophthalmological abnormalities, followed by significant improvement in motor
      control and behavior, which gradually subsides. Parenteral administration is
      superior to oral. Tolerance to the drug is observed. The presence of electrical
      stimulation of the spinal cord complements the action of the drug. When
      electrical stimulation is withdrawn, the effect of the drug reproduces the effect
      of the electrical stimulation. It is suggested there is a defect in
      cholinesterase in multiple sclerosis patients, and its reactivation may have a
      significant relationship to signs and symptoms.

PMID- 1357925
TI  - Acupuncture treatment for psoriasis: a retrospective case report.
AB  - We treated 61 cases of psoriasis with acupuncture, including 25 patients with
      complications of joint involvement and two cases with scleroderma additionally.
      All of the patients had failed to respond to their prior conventional western
      medical management. 25 patients were males and 36 were females. Their ages ranged
      from 22 to 84 years, with an average of about 52 years. There was no significant
      difference of the average ages between the sexes. Most of them (about 61%) had
      quite extensive involvement of the body. The average of duration of their illness
      was over 16 years, ranging from two to 65 years. They received an average of
      about nine sessions of acupuncture treatment, ranging from one to 15. Almost one
      third (19) of them had eleven to thirteen sessions. With the acupuncture
      treatment, about one-half (30) of the 61 patients had complete or almost complete
      clearance of the skin lesions. About a quarter (14 patients) of them had a
      clearance of about two thirds of the skin lesions. Eight of them had a clearance
      of one third of the skin lesions. Nine patients had minimal or no improvement.
      Our experience indicates that acupuncture is induced an effective therapeutic
      modality for psoriasis, particularly when the western medical management is
      unsuccessful. We speculated about the possible involvement of the cutaneous
      reticuloendothelial system in the clearance of the skin lesions.

PMID- 1357926
TI  - Hypothalamic paraventricular nucleus plays a role in acupuncture analgesia
      through the central nervous system in the rat.
AB  - This work investigates the effect of hypothalamic paraventricular nucleus (PVN)
      on acupuncture analgesia in the rat. Electrical stimulation of PVN or injection
      of L-glutamate sodium into PVN could enhance the analgesic effect induced by
      acupuncture Zusanli (St. 36) while the electrical cauterization of PVN is
      decreased; Removal of the pituitary could not influence the effect of enhancing
      acupuncture analgesia induced by the injection of L-glutamate sodium into PVN.
      These results suggest that PVN might play an important role in acupuncture
      analgesia through central nervous system.

PMID- 1357927
TI  - Frequency-dependent effects of sine-wave cranial transcutaneous electrical nerve
      stimulation in human subjects.
AB  - In a double-blind protocol, ninety healthy volunteer subjects received 30 minutes
      of constant current sine-wave cranial transcutaneous electrical nerve stimulation
      (TENS) of 5 Hertz (Hz), 100 Hz, or 2000 Hz frequency (current maintained below .5
      mA for safety), placebo TENS, or no treatment. The five groups were compared on
      pre- to posttreatment changes in blood pressure, heart rate, peripheral
      temperature, and anxiety. Analysis showed significant reductions in systolic and
      diastolic blood pressure and heart rate after 100 Hz cranial TENS as compared to
      the other groups. No other differences achieved significance.

PMID- 1357928
TI  - The scientific rationale, clinical practice, and future of acupuncture in the
      United States.

PMID- 1357929
TI  - Microbial Infections: Role of Biological Response Modifiers. Proceedings of an
      international conference. Tampa, Florida, May 29-31, 1991.

PMID- 1357930
TI  - Bacterial polysaccharides, endotoxins, and immunomodulation.
AB  - These studies show that at least some--though certainly not all--of the adjuvant
      effects of LPS and its derivatives can be attributed to its ability to eliminate
      the inhibitory effects of Ts which are activated during the course of a normal
      immune response. The ability of nontoxic MPL to act in this fashion suggests that
      it can be used as a safe and acceptable alternative to Freund's complete adjuvant
      to increase the immunogenicity of poorly immunogenic antigens. More important,
      the ability of MPL to eliminate the expression of Ts activity, without adversely
      influencing other T cell functions (e.g., Th, Ta, and Tc activity) makes its use
      as an adjuvant even more promising since it can then permit those T cell
      functions to be expressed in a much more efficient manner. Obviously, this would
      have great significance for the development of tumor immunity.

PMID- 1357931
TI  - [Management of femoral neck fractures with the spongiosa screw and the dynamic
      hip screw].
AB  - Between 1983 and 1987 419 patients with femoral neck fractures were operated on
      at the University Clinics of Graz. In 120 patients we could preserve the head of
      the femur doing an internal fixation with cancellous bone screws or DHS. 68 of
      them we personally could control with a mean follow up of 45.2 months. The most
      important complications were the necrosis of the head which were observed in
      19.1% of our patients and the non union which occurred in 5.8% but not all these
      patients required reoperation.

PMID- 1357932
TI  - [Management of unstable pertrochanteric and per- to subtrochanteric femoral
      fractures with the dynamic hip screw].
AB  - The operative treatment of fractures of the proximal end of femur with the
      dynamic hip screw (DHS) permits a weight-bearing stable osteosynthesis. In 5.2
      years between 1985 and 1990 531 patients were treated with a DHS. The average age
      was 75 years. This method of osteosynthesis was also performed in 59 patients
      with unstable per- or per-subtrochanteric fractures. Complications such as
      pseudarthrosis, necrosis or penetration of the head of femur, implant bending or
      breaking were not observed. The dynamic hip screw is a valid procedure for an
      early and weight-bearing treatment also for unstable pertrochanteric fractures of
      the femur with special benefits for the elderly.

PMID- 1357933
TI  - [Results of angled plated osteosynthesis in per- and subtrochanteric fractures in
      the elderly].
AB  - From 1/86 to 12/89 62 old patients (average age: 82.6) with intertrochanteric and
      subtrochanteric fractures underwent surgery by using angeled plates. The
      postoperative course showed complications in 32.2%, while only 1 patient died. In
      3 of 5 cases with dislocation of the angeled plate re-osteosynthesis was
      performed. 4 other complications (2x haematoma, 2x wound dehiscence) needed
      further surgery. During the first three months 3 other dislocations occurred. In
      two cases re-osteosynthesis was carried out. Due to these results and the high
      rate of complications we are of the opinion that the indication for the use of
      the angeled plate osteosynthesis in old patients has to be limited in favor of
      other methods like the dynamic hip screw or total hip replacement.

PMID- 1357934
TI  - [The value of Ender nailing in hip para-articular femoral fractures in
      gerontologic traumatology. Ender nailing--hip para-articular femoral fractures-
      gerontologic traumatology].
AB  - Nailing according to Ender is one of several competing methods of osteosynthesis
      for treating per- and subtrochanteric fractures of the femur in geronto
      traumatology. Within 5 years we have treated 62 geriatric patients by this
      procedure. The average-age of our patients was about 76 years. Only 20 of them
      were able to be examined after a time of ca. 37 months post operationem.
      Intraoperative complications were backing out of the femur corticalis at the
      entry hole, followed by perforations of the head or neck of the femur. In one
      case we saw a supracondylar fracture. In the postoperative period we mostly found
      dislocations of the nails to cranial or caudal. Moreover there were one wound
      infect and one pseudarthrosis. The mortality rate came to 6.5% and was never
      caused by the method. When leaving the hospital the majority of the elderly
      patients was mobilized and able to walk. In spite of reduction of function of hip
      and knee and external rotation deformity and shortened legs the patients declared
      to be content with the result of the operation. Important geronto-traumatological
      aspects of the Endernailing-method could be seen in the simple procedure, the
      short operating time, a minimal surgical trauma and a diminishing of the risk of
      the mostly multi-morbid patients. Regarding the great number of specific
      complications competing methods are going on to be preferred. Meanwhile the
      application of Endernails is an exception in geronto-traumatology.

PMID- 1357935
TI  - [Alloplastic replacement of the anterior cruciate ligament. Material technical
      and biomechanical principles, surgical technique].
AB  - The Trevira-ligament of Polyaethylenter-ephthalat (= Trevira-hochfest 730) seems
      to be the best qualified replacement of the anterior cruciate ligament at the
      present. It meets all material and technical requirements and makes allowances
      for all biomechanical knowledges. The modified over-the-top-technique by
      arthroscopy or mini-arthrotomy (minimal operative trauma) makes it possible to
      conserve still existing ligamentous and soft tissue and guarantees the post
      operative immediate functional therapy. A potential reinstability--independent of
      each cause--doesn't imply worse starting conditions and enables corrections
      including the substitute of a ruptured synthetic ligament.

PMID- 1357936
TI  - [Economic information and counseling responsibility of the physician: also
      "financial therapy" of the patient?].

PMID- 1357937
TI  - [Tarsal tunnel syndrome after fibular ligament repair. A rare complication of
      surgical therapy of chronic instability of the ankle joint ligament].
AB  - A case of tarsal tunnel syndrome following a reconstructive procedure with repair
      of chronic ankle instability using periosteal flap is reported. Two pathogenetic
      factors have to be discussed as possible causes for this complication. Dissection
      of the medial retinaculum was performed. With this procedure the patient is
      complaints could be removed.

PMID- 1357938
TI  - Application of microsatellite DNA polymorphisms to linkage mapping of Tourette
      syndrome gene(s).

PMID- 1357939
TI  - Treatment of Tourette syndrome with neuroleptic drugs.

PMID- 1357940
TI  - Non-rheumatic inflammatory diseases.

PMID- 1357941
TI  - Development and inhibition of mouse ear oedema induced with capsaicin.
AB  - Oedema was induced in one ear of male mice of the CFLP strain with capsaicin
      solution (10 microliters/40 micrograms/ear). The development in time and the
      extent of the oedema were determined by the oedema-disk gravimetric technique.
      The maximum oedema was attained in less than 1 h, and there was, subsequently, a
      gradual decrease. The extent of the mouse ear oedema induced in this way and
      measured after 60 min was inhibited to a statistically significant degree and in
      a dose-dependent manner by the antihistamine chloropyramine, the antihistamine
      antiserotonin cyproheptadine, the non-steroidal anti-inflammatory agent
      piroxicam, the prostaglandin antagonist di-4-phloretin phosphate, and the
      lipoxygenase inhibitor nordihydroguairetic acid. The method proved suitable for
      the detection of oedema and for the biologically quantitative determination of
      the state of desensitization induced with capsaicin.

PMID- 1357942
TI  - ["In-dartos" orchidopexy in the treatment of cryptorchism].
AB  - Undescended testis is a common congenital abnormality. The main complications are
      infertility and venue of malignant testicular tumor. If early orchiopexy can
      prevent infertility, it remains a high risk of venue of a malignant tumor. So,
      the best technique of orchiopexy is that which allows an easy clinical follow-up
      of the undescended testis after surgical treatment, and doesn't involv the
      hematoseminal barrier. From the analysis of fourty cases of scrotal pouch
      orchiopexy and a review of the literature, it appears that this procedure is
      efficient and gives more than 90% of good results.

PMID- 1357943
TI  - [Neurotransmission and the lower urinary system].
AB  - Various substances, called neurotransmitters, act as a chemical relay between the
      nervous and the tissue of the lower urinary tract. Some play also a role inside
      the muscle cell modulating the activity of the myofibrils. To allow a better
      pharmacochemical approach, these substances are described, their activity
      analyzed, with the purpose of helping specialists concerned by investigation or
      treatment of the lower urinary tract, to be able to act on their activity or
      change their pathologic abnormalities.

PMID- 1357944
TI  - [Effect of YM-12617 (amsulosin hydrochloride) on lower urinary tract function in
      the female decerebrate dog].
AB  - The effect of YM-12617 on the lower urinary tract function was studied by
      combined recording of cystometry and external sphincter electromyogram (EMG) in
      11 female decerebrate dogs. Reflex micturitions were induced by bladder filling
      before and after YM-12617 administration. Statistical analysis was carried out on
      the urodynamic parameters. YM-12617 in a dose of 10 micrograms/kg significantly
      decreased micturition threshold pressure during the collecting phase. In the
      urodynamic parameters of the emptying phase there was a significant decrease in
      contraction pressure at 10 and 30 micrograms/kg.

PMID- 1357945
TI  - [Prader-Willi syndrome associated with chromosomal aberration: report of a case].
AB  - A male case of Prader-Willi syndrome (2.8 years in age) with an interstitial
      deletion of a chromosome affecting 15q 11-12 region is reported. The chief
      complaints were hypoplastic scrotum and defect of bilateral scrotal content. The
      clinical features were short stature, obesity, delayed mental development,
      bilateral cryptorchidism, hypogenitalism, hypopigmentation, and bilateral
      moderate vesicoureteral reflux with a history of muscular hypotonia. Bilateral
      orchidopexy was done. Endocrinologically both base values of luteinizing hormone
      (LH) and follicle stimulating hormone (FSH) were normal although LH reserve
      function was impaired on gonadotropin releasing hormone (GnRH) test. Testosterone
      response was normal by the stimulation of human chorionic gonadotropin. An
      interstitial deletion of proximal 15q, and pituitary-gonadal axis in Prader-Willi
      syndrome are discussed in relation to the clinical features and therapy.

PMID- 1357946
TI  - Protection against histamine-induced bronchoconstriction by loratadine.
AB  - In a simple blind pilot study we have examined the protective effect of
      loratadine, a new H1 histamine receptor antagonist, against bronchoconstriction
      induced by histamine inhalation. Six patients with an episodic or continuing
      obstructive bronchial disease and proven bronchial hyperreactivity were submitted
      to two identical histamine challenges, first without premedication and then after
      three days' treatment with 10 mg loratadine daily. The mean FEV1 fall in the
      first test after histamine inhalation was 33% and in the second test after
      pretreatment with loratadine only 3.3% (p less than 0.01). Five out of six
      patients have shown complete protection against histamine-induced
      bronchoconstriction, in one patient the protection was partial. We conclude that
      loratadine effectively inhibits histamine-induced bronchoconstriction and could
      be useful in the prophylactic treatment of asthma and obstructive bronchitis.

PMID- 1357948
TI  - Low CD4 cell count in HIV-negative persons.

PMID- 1357947
TI  - National guidelines for the management of asthma in adults.
AB  - Asthma is now considered primarily an inflammatory disease in which bronchospasm
      occurs secondary to airway inflammation. Management strategies include the use of
      inhaled anti-inflammatory agents, notably inhaled corticosteroids and cromolyn.
      Mild intermittent asthma may be treated with inhaled bronchodilators. Moderate
      asthma should be treated with an inhaled anti-inflammatory agent in addition to
      an inhaled beta agonist. If symptoms persist, an oral bronchodilator (either a
      beta-adrenergic agonist or theophylline) should be added. Therapy for severe
      asthma includes combinations of the foregoing medications, with the possible
      addition of oral corticosteroids. Other aspects of management include the use of
      a spacer device with inhaler therapy, control of concomitant allergies and
      triggering factors such as chronic sinusitis, tobacco smoke and gastroesophageal
      reflux, and home use of a portable peak flow meter to monitor the disease.

PMID- 1357949
TI  - A symposium: Heart failure management in the 1990s: the role of lisinopril.
      Montreux, Switzerland, November 7-8, 1991.

PMID- 1357950
TI  - Autocrine and paracrine mechanisms in the pathophysiology of heart failure.
AB  - At the cellular and molecular level the transition to heart failure is a complex
      process that involves structural adaptation, not only of the heart, but of
      peripheral vasculature and renal tissues as well. Recent studies have suggested
      that autocrine, paracrine, and circulating biologically active mediators activate
      events that result in the concerted failure of adaptive mechanisms and the
      ultimate depression of cardiac myocyte function. Greater understanding of these
      local mechanisms in the future may lead to drug therapies that can selectively
      block these mechanisms and prevent the progression from compensation to overt
      heart failure.

PMID- 1357952
TI  - Symposium: Systemic Hypertension: Contribution of Trandolapril, a New Angiotensin
      Converting Enzyme Inhibitor, Toward Patient Protection. 14th scientific meeting
      of the International Society of Hypertension. Madrid, Spain, June 13, 1992.

PMID- 1357951
TI  - Beta-blocking effect of propafenone based on spectral analysis of heart rate
      variability.
AB  - RR variability was analyzed in 15 patients with ventricular arrhythmias to
      evaluate whether the antiarrhythmic action of propafenone is associated with
      alteration of neural control mechanisms. Before drug administration, spectral
      analysis of RR variability was characterized by 2 major components at low and
      high frequency, which are considered to reflect sympathetic and parasympathetic
      modulation of the heart period. After propafenone (600 to 900 mg/day), there was
      a marked reduction in RR variance (826 +/- 184 to 412 +/- 77 ms2; p < 0.05),
      although the mean RR interval was unchanged. The drug significantly reduced the
      low-frequency component (52 +/- 6 to 28 +/- 4 nu) and augmented the high
      frequency component (39 +/- 6 to 55 +/- 5 nu). As a result, the low-/high
      frequency ratio (an index of sympathovagal balance) decreased from 2.0 +/- 0.4 to
      0.6 +/- 0.1. A positive correlation between serum levels and drug-induced changes
      in the low-frequency component was also observed. Furthermore, the increase in
      the low-frequency component induced by tilt (53 +/- 5 to 79 +/- 3 nu) was
      markedly attenuated after drug administration (27 +/- 5 to 54 +/- 7 nu). Thus,
      propafenone administration is associated with changes in spectral components that
      are consistent with a beta-blocking effect of the drug.

PMID- 1357953
TI  - Early results with bilateral internal mammary artery grafting in coronary
      reoperations.
AB  - In recent years, use of the internal mammary artery (IMA) as first graft of
      choice has been expanded with bilateral and sequential grafts in primary
      myocardial revascularization. The use of bilateral IMA grafts in reoperation has
      seldom been reported. The experience and early results with bilateral IMA
      grafting in 47 patients undergoing coronary reoperation are described. Hospital
      mortality was 6.3%. Four patients had postoperative signs of low cardiac output,
      and 4 had a perioperative myocardial infarction. At follow-up (18 +/- 18 months),
      2 cardiac-related, late deaths were noted. Thirteen patients (29%) improved 1 New
      York Heart Association class, and 28 (63%) improved > 1 class. In 1 of 44
      surviving patients, operation did not result in a decrease in angina. On the
      basis of the early results, the bilateral use of the IMA in coronary reoperation
      appears justified.

PMID- 1357954
TI  - Regression of left ventricular hypertrophy in systemic hypertension with beta
      blockers (propranolol, atenolol, metoprolol, pindolol and celiprolol).

PMID- 1357955
TI  - Workshop on dietary fatty acids and thrombosis. Airlie, Virginia, March 18-20,
      1991.

PMID- 1357956
TI  - p53 and c-erbB-2 protein expression in breast carcinomas. An immunohistochemical
      study including correlations with receptor status, proliferation markers, and
      clinical stage in human breast cancer.
AB  - Receptor status, proliferative activity, loss of differentiation, inactivation of
      tumor suppressor genes, and overexpression of oncogenes are related events that
      may affect the prognosis of patients with breast cancer. Ninety-seven unselected
      breast carcinomas were immunostained for estrogen and progesterone receptors, Ki
      67 proliferation-associated antigen, p53 tumor suppressor gene product (p53), and
      c-erbB-2 protein. Immunohistochemical results and clinical data were compared.
      Altered p53 expression (regarded as indirect indication of inactivating gene
      alterations) was found in 25.8% of cases and was associated with a high Ki-67
      labeling index, high mitotic count, and high histologic grade, with c-erbB-2
      overexpression, and with negative estrogen and progesterone receptor status. p53
      immunostaining could be found also in cytologic samples and correlated with p53
      immunoreactivity on frozen sections of the corresponding tumors. c-erbB-2 protein
      overexpression was seen in 24.7% of cases and was associated with p53 altered
      expression and negative receptor status. Double immunohistochemical staining
      showed p53 and c-erbB-2 immunoreactivity in the same cells. Median and mean +/-
      standard deviation Ki-67 labeling index values were 15 and 16.32 +/- 10.05,
      respectively. Ki-67 labeling index was correlated with high mitotic count and was
      positively associated with histologic grade, negative progesterone receptor
      status, and p53 expression. Estrogen receptor status was not associated with any
      histologic or clinical parameters, whereas progesterone receptor status was
      associated with grading. The direct relation of p53 protein alterations with c
      erbB-2 overexpression may be interpreted in light of the multistep model of tumor
      progression. Cases with altered expression of both p53 and c-erbB-2 proteins
      could be interpreted as having lost one inhibitory control mechanism of cell
      proliferation and having gained one activator of the malignant potential.
      However, in comparing cases with the p53 + c-erbB-2 + phenotype with cases
      showing positivity for only one of these gene products, no association with
      higher stages was seen. Detection of p53 altered expression on cytologic samples
      of malignant tumors may have diagnostic relevance, and p53 immunostaining may
      prove to be an additional diagnostic criterion in cytologic diagnosis.

PMID- 1357957
TI  - Chronic 3,4-methylenedioxymethamphetamine (MDMA) use: effects on mood and
      neuropsychological function?
AB  - 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a selective serotonin (5
      HT) neurotoxin in animals. There is now preliminary evidence in humans of 5-HT
      deficits associated with extensive use of MDMA. In order to begin to describe the
      cognitive and mood effects of chronic MDMA use, nine individuals with extensive
      MDMA use histories were studied. Despite the absence of memory deficits on
      clinical examination, a pattern of mild-to-moderate impairment was observed on
      both the Initial and Delayed Paragraph Tests of the Wechsler Memory Scale; eight
      of the subjects had at least mild impairment on at least one test in the
      neuropsychological battery. Despite previously reported suggestive evidence of 5
      HT deficit in this group, none reported depressed mood or met clinical criteria
      for an affective disorder at the time of testing. These preliminary findings
      raise concern about possible detrimental effects of MDMA use on
      neuropsychological function for future systematic study and they highlight
      important issues regarding the effects of 5-HT deficits on cognitive function and
      mood regulation.

PMID- 1357958
TI  - Transglutaminase and factor XIII in intestinal disorders.

PMID- 1357960
TI  - Seroepidemiology of California and Bunyamwera serogroup bunyavirus infections in
      humans in California.
AB  - Several human populations in California were surveyed cross-sectionally and
      longitudinally for neutralizing antibodies to selected arthropod-borne
      bunyaviruses in the California and Bunyamwera serogroups. Overall, the prevalence
      of antibodies to California serogroup viruses was 6.4% in 702 individuals sampled
      during 1963-1988. Comparative antibody titers in individual sera indicated that
      4.1% and 1.6% of these infections were caused by viruses similar or identical to
      Jamestown Canyon and California encephalitis, respectively. Evidence of prior
      infection with the Jamestown Canyon serotype was found in 10% of 118 humans
      employed outdoors in high elevation areas and sampled in 1988, including 5 of 16
      persons (31%) employed as rangers patrolling in remote forests and meadows. This
      probably reflects increased exposure to bites of boreal mosquitoes that breed in
      pools of melted snow. Antibodies to Bunyamwera serogroup viruses, including the
      Northway serotype, which was recently shown to be enzootic in California, were
      found in only 2 of 702 humans studied. No seroconversions were detected to
      selected California or Bunyamwera serogroup viruses in paired samples from 392
      humans, including 349 patients with acute central nervous system disease or
      undifferentiated febrile illnesses who were sampled during 1963-1988, and thus
      these viruses are currently unconfirmed as human pathogens in California.

PMID- 1357959
TI  - Menopause and serum cholesterol: differences between blacks and whites. The
      Minnesota Heart Survey.
AB  - The relation between menopause and serum total and high-density-lipoprotein
      cholesterol was examined by the Minnesota Heart Survey in a cross-sectional,
      population-based study of 344 black women and 474 white women aged 35-54 years
      from the Twin Cities metropolitan area in 1985-1986. Analysis of covariance was
      used to examine differences in serum total and high-density-lipoprotein
      cholesterol in black women and white women by menopausal status, adjusting for
      the effects of age, educational level, cigarette smoking, body mass index,
      exercise, alcohol consumption, diabetes mellitus, sex hormone, beta blocker, and
      diuretic use. Among whites, adjusted serum total cholesterol was 13 mg/dl higher
      in postmenopausal than in premenopausal women (p less than 0.002). Black
      postmenopausal women had slightly higher serum total cholesterol than did their
      premenopausal counterparts (5.4 mg/dl). However, this was not statistically
      significant. An interaction term in a linear regression model confirmed a racial
      difference in the total cholesterol association with menopause (p less than
      0.02). The higher total cholesterol levels observed in white postmenopausal women
      were mainly among those with natural menopause (20.7 mg/dl higher than
      premenopausal, p less than 0.0003) and those with a hysterectomy and at least one
      intact ovary (11.0 mg/dl higher, p = 0.05). Among black women, only the subgroup
      with a hysterectomy and a bilateral oophorectomy had a significantly higher serum
      total cholesterol (19.9 mg/dl higher than premenopausal, p less than 0.05). There
      was no significant association between high-density-lipoprotein cholesterol and
      any type of menopause in either black women or white women. Our findings may
      reflect a true physiologic difference in the relation between menopause and serum
      total cholesterol between American blacks and whites. The lack of a significant
      association between menopause and high-density-lipoprotein cholesterol in either
      race raises the possibility that menopause may not affect atherosclerosis risk
      via reduced high-density-lipoprotein cholesterol.

PMID- 1357961
TI  - Symptomatic La Crosse virus infections of the central nervous system: a study of
      risk factors in an endemic area.
AB  - In most years, La Crosse virus is the most common cause of reported mosquito
      borne illness in the United States. The authors conducted a case-control study to
      determine if behavioral and environmental factors influenced the risk of La
      Crosse virus illness. Data were gathered on 31 serologically confirmed cases and
      60 age-, sex-, and geography-matched controls in West Virginia in 1987 and 1988.
      Univariate analysis revealed minimal elevation of disease risk (odds ratios (ORs)
      less than 2.0) with increased time outdoors, non-use of insect repellent, non-use
      of air conditioning, lack of screened windows, and not wearing protective
      clothing. Univariate and multivariate analysis indicated that the presence of
      tree holes significantly increased disease risk (OR = 8.5 for greater than or
      equal to 1 tree hole vs. 0 tree holes). The following factors may also increase
      disease risk, although the findings were not statistically significant: discarded
      tires (OR = 3.2 for greater than or equal to 10 tires vs. 0-9 tires); non-tire
      artificial containers (OR = 4.1 for greater than or equal to 6 containers vs. 0-5
      containers); and close proximity of the house to the forest edge (OR = 3.2 for 0
      49 ft (0-14.9 m) vs. greater than or equal to 50 ft (greater than or equal to
      14.9 m)). The authors conclude that the presence of natural breeding sites (tree
      holes) is an important risk factor for La Crosse virus illness. These results may
      be important in guiding future efforts aimed at preventing infection with La
      Crosse virus.

PMID- 1357962
TI  - Trisomy 15 with loss of the paternal 15 as a cause of Prader-Willi syndrome due
      to maternal disomy.
AB  - Uniparental disomy has recently been recognized to cause human disorders,
      including Prader-Willi syndrome (PWS). We describe a particularly instructive
      case which raises important issues concerning the mechanisms producing
      uniparental disomy and whose evaluation provides evidence that trisomy may
      precede uniparental disomy in a fetus. Chorionic villus sampling performed for
      advanced maternal age revealed trisomy 15 in all direct and cultured cells,
      though the fetus appeared normal. Chromosome analysis of amniocytes obtained at
      15 wk was normal in over 100 cells studied. The child was hypotonic at birth, and
      high-resolution banding failed to reveal the deletion of 15q11-13, a deletion
      which is found in 50%-70% of patients with PWS. Over time, typical features of
      PWS developed. Molecular genetic analysis using probes for chromosome 15 revealed
      maternal disomy. Maternal nondisjunction with fertilization of a disomic egg by a
      normal sperm, followed by loss of the paternal 15, is a likely cause of confined
      placental mosaicism and uniparental disomy in this case of PWS, and advanced
      maternal age may be a predisposing factor.

PMID- 1357963
TI  - High-resolution mapping of the X-linked hypohidrotic ectodermal dysplasia (EDA)
      locus.
AB  - The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously
      localized to the subchromosomal region Xq11-q21.1. We have extended our previous
      linkage studies and analyzed linkage between the EDA locus and 10 marker loci,
      including five new loci, in 41 families. Four of the marker loci showed no
      recombination with the EDA locus, and six other loci were also linked to the EDA
      locus with recombination fractions of .009-.075. Multipoint analyses gave support
      to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and
      PGK1 loci distal to EDA. Further ordering of the loci could be inferred from a
      human/rodent somatic cell hybrid derived from an affected female with EDA and an
      X;9 translocation and from studies of an affected male with EDA and a
      submicroscopic deletion. Three of the proximal marker loci, which showed no
      recombination with the EDA locus, when used in combination, were informative in
      92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453
      had heterozygosities of 72% and 76%, respectively, and when used jointly, they
      were doubly informative in 52% of females. The human DXS732 locus was defined by
      a conserved mouse probe pcos169E/4 (DXCrc169 locus) that cosegregates with the
      mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of
      recombination between EDA and the DXS732 locus lends support to the hypothesis
      that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain
      candidate sequences for the Ta and EDA genes, respectively.

PMID- 1357964
TI  - DNA polymorphism of alkaline phosphatase isozyme genes: linkage disequilibria
      between placental and germ-cell alkaline phosphatase alleles.
AB  - The use of human placental alkaline phosphatase (PLAP) cDNA as a probe allows the
      detection and identification of restriction DNA fragments derived from three
      homologous genes, i.e., intestinal alkaline phosphatase (AP), germ-cell AP
      (GCAP), and PLAP. In previous RFLP studies we have reported linkage disequilibria
      between an RsaI and two PstI (a and b) polymorphic restriction sites and
      electrophoretic types of PLAP. In this report we present evidence that, in spite
      of the strong correlation with PLAP types, PstI(b) is an RFLP of GCAP. The data
      indicate close linkage between the PLAP and GCAP loci.

PMID- 1357965
TI  - X-linked nephrogenic diabetes insipidus: from the ship Hopewell to RFLP studies.
AB  - Nephrogenic diabetes insipidus (NDI; designated 304800 in Mendelian Inheritance
      in Man) is an X-linked disorder with abnormal renal and extrarenal V2 vasopressin
      receptor responses. The mutant gene has been mapped to Xq28 by analysis of RFLPs,
      and tight linkage between DXS52 and NDI has been reported. In 1969, Bode and
      Crawford proposed, under the term "the Hopewell hypothesis," that most cases in
      North America could be traced to descendants of Ulster Scots who arrived in Nova
      Scotia in 1761 on the ship Hopewell. They also suggested a link between this
      family and a large Mormon pedigree. DNA samples obtained from 13 independent
      affected families, including 42 members of the Hopewell and Mormon pedigrees,
      were analyzed with probes in the Xq28 region. Genealogical reconstructions were
      performed. Linkage between NDI and DXS304 (probe U6:2.spl), DXS305 (St35-691),
      DXS52 (St14-1), DXS15 (DX13), and F8C (F814) showed no recombination in 12
      families, with a maximum lod score of 13.5 for DXS52. A recombinant between NDI
      and DXS304, DXS305, was identified in one family. The haplotype segregating with
      the disease in the Hopewell pedigree was not shared by other North American
      families. PCR analysis of the St14 VNTR allowed the distinction of two alleles
      that were not distinguishable by Southern analysis. Carrier status was predicted
      in 24 of 26 at-risk females. The Hopewell hypothesis cannot explain the origin of
      NDI in many of the North American families, since they have no apparent
      relationship with the Hopewell early settlers, either by haplotype or by
      genealogical analysis. We confirm the locus homogeneity of the disease by linkage
      analysis in ethnically diverse families. PCR analysis of the DXS52 VNTR in NDI
      families is very useful for carrier testing and presymptomatic diagnosis, which
      can prevent the first manifestations of dehydration.

PMID- 1357966
TI  - Linkage disequilibrium among RFLPs at the insulin-receptor locus despite
      intervening Alu repeat sequences.
AB  - Multiple mutations of the insulin receptor (INSR) gene have been identified in
      individuals with extreme insulin resistance. These mutations have included
      recombination events between Alu repeat units in the tyrosine kinase-encoding
      beta-chain region of the gene. To evaluate the influence of Alu and dinucleotide
      repetitive sequences on recombination events within the insulin receptor gene, I
      examined the degree of linkage disequilibrium between RFLP pairs spanning the
      gene. I established 228 independent haplotypes for seven RFLPs (two each for
      PstI, RsaI, and SstI and one for MspI and 172 independent haplotypes which
      included an additional RFLP with BglII) from 19 pedigrees. These RFLPs span > 130
      kb of this gene, and my colleagues and I previously demonstrated that multiple
      Alu sequences separate RFLP pairs. Observed haplotype frequencies deviated
      significantly from those predicted. Pairwise analysis of RFLP showed high levels
      of linkage disequilibrium among RFLP in the beta-chain region of the insulin
      receptor, but not between alpha-chain RFLPs and those of the beta-chain.
      Disequilibrium was present among beta-chain RFLPs, despite separation by one or
      more Alu repeat sequences. The very strong linkage disequilibrium which was
      present in sizable regions of the INSR gene despite the presence of both Alu and
      microsatellite repeats suggested that these regions do not have a major impact on
      recombinations at this locus.

PMID- 1357967
TI  - An association between manic-depressive illness and a pseudoautosomal DNA marker.

PMID- 1357968
TI  - Helicobacter pylori seroprevalence in patients with rheumatoid arthritis: effect
      of nonsteroidal anti-inflammatory drugs and gold compounds.
AB  - PURPOSE: To investigate the relationship between Helicobacter pylori infection
      and nonsteroidal anti-inflammatory drug (NSAID) intolerance and the effect of
      gold use on the seroprevalence of H. pylori. PATIENTS AND METHODS: We examined
      the frequency of discontinuation of NSAIDs in 132 unselected patients with
      rheumatoid arthritis attending an outpatient subspecialty clinic, and the effect
      of gold compound use on the seroprevalence (by IgG enzyme-linked immunosorbent
      assay) of H. pylori infection in this population. Logistic and multivariate
      regression analysis was performed adjusting for age, gender, ethnic origin,
      history of ulcer, and duration of rheumatoid arthritis. RESULTS: Fifty-four
      patients had a positive serology for H. pylori (41%). Twenty-seven of the
      seropositive patients (50%), versus 45 of the seronegative patients (57.7%), had
      to discontinue NSAIDs (aspirin and/or nonaspirin) at least once since their
      diagnosis of rheumatoid arthritis because of gastrointestinal side effects (odds
      ratio [OR], 0.93; 95% confidence interval [CI], 0.63 to 1.38). Forty-one of the
      seropositive patients (76%) had received gold compounds as compared with 62 of
      the seronegative patients (79.5%) (OR: 0.96; 95% CI: 0.61 to 1.50). CONCLUSION:
      We did not find any relationship between H. pylori seropositivity and NSAID
      intolerance in patients with rheumatoid arthritis. In addition, our results do
      not demonstrate a reduction in H. pylori seroprevalence in rheumatoid arthritis
      patients treated with gold compounds.

PMID- 1357969
TI  - Parental origin determination in thirty de novo Robertsonian translocations.
AB  - Cytogenetic heteromorphisms and restriction fragment length polymorphisms were
      used to assign the parental origins of 30 de novo non-homologous Robertsonian
      translocations. The balanced and unbalanced translocations studied included 20
      rob(14q21q) four rob(13q14q)four rob(15q21q) one rob(13q15q), and one
      rob(13q21q). Significantly more maternally (26/30) than paternally (4/30) derived
      de novo translocations were noted and all rob(14q21q) ascertained through
      unbalanced probands (20/20) were maternal in origin. Interestingly, 12/13
      probands who were trisomic and informative for proximal chromosome 21q loci were
      homozygous for the markers tested. Segregation (2:1) of the Robertsonian
      translocation into one daughter cell in meiosis I and subsequent failure of the
      chromosome 21 chromatids to separate in meiosis II may account for our
      observation of homozygosity for proximal chromosome 21 loci in the majority of de
      novo rearrangements tested.

PMID- 1357970
TI  - Diagnosis of arylsulfatase A deficiency.
AB  - Metachromatic leukodystrophy (MLD) is a neurologically devastating autosomal
      recessive disorder in humans associated with deficient arylsulfatase A activity.
      However, clinically normal individuals described as being pseudo-arylsulfatase-A
      deficient also demonstrate the same deficiency. Genotypically, they may be
      homozygous for the pseudodeficiency mutation (associated with 2 A-->G transitions
      in the cDNA of arylsulfatase A) or heterozygous with one pseudodeficiency and one
      MLD allele. Using as examples 2 families in which the pseudo deficiency condition
      occurs either independently or together with MLD, we demonstrate the utility of a
      proposed diagnostic protocol to provide complete genotype identification of
      individuals suffering from arylsulfatase A deficiency. Patient fibroblasts are
      extracted for DNA and a cytoplasmic fraction, which is used for arylsulfatase A
      enzyme assay. This will identify an arylsulfatase A-deficient group, which is
      further analyzed electrophoretically. Cells from the clinically affected patients
      with MLD are completely deficient in arylsulfatase A activity, whereas those from
      the pseudodeficient individuals demonstrate a characteristic residual
      arylsulfatase A activity detectable only after electrophoresis. Within this
      pseudodeficient group, gene amplification of DNA specific for the A-->G mutations
      will distinguish between those who are homozygous for the pseudodeficiency allele
      and those who are compound heterozygous for the pseudodeficiency and MLD alleles.
      This protocol of complete genotype identification requires only about 10(6)
      fibroblasts (1 x 100 mm dish) and 2 days to complete. Such variant-specific
      genotype identification increases accuracy and prognostic value of the diagnosis.
      It will likely become the preferred choice for diagnosis of genetic disease in
      the future as more variant-specific mutations are identified at the molecular
      level.

PMID- 1357971
TI  - Takayasu's arteritis as a cause of renovascular hypertension in Asian countries.

PMID- 1357972
TI  - Hemorrhagic fever with renal syndrome in an endemic area of Greece.
AB  - From 1983 to 1990, 32 patients with hemorrhagic fever with renal syndrome (HFRS)
      were admitted to our hospital. The diagnosis was confirmed by high IgM type
      titers of antibodies to Hantaan virus. All patients presented with serum and
      urine abnormalities suggesting renal involvement. Serum creatinine was elevated
      and ranged between 1.8 and 14.3 mg/dl. Proteinuria ranged between 0.5 and 6.4
      g/24 h. Seven patients died due to shock or hemorrhage, while 6 patients were
      supported by hemodialysis or peritoneal dialysis. Five of them had a complete
      recovery. Two patients were discharged with some degree of renal impairment which
      remained stable 12-15 months later. Kidney biopsy in the first patient performed
      1 year after his discharge revealed some degree of interstitial fibrosis and
      tubular atrophy as well as an area with ischemic and sclerosed glomeruli. We
      conclude that HFRS in Greece is a severe disease with a high mortality rate. The
      disease may cause chronic renal failure in a limited number of patients.

PMID- 1357973
TI  - The relationship of quantitative nuclear morphology to molecular genetic
      alterations in the adenoma-carcinoma sequence of the large bowel.
AB  - The relationship of abnormal nuclear morphology to molecular genetic alterations
      that are important in colorectal tumorigenesis is unknown. Therefore, Feulgen
      stained isolated nuclei from 22 adenomas and 42 carcinomas that had been analyzed
      for ras gene mutations and allelic deletions on chromosomes 5q, 18q, and 17p were
      characterized by computerized image analysis. Both nuclear area and the nuclear
      shape factor representing irregularity correlated with adenoma-carcinoma
      progression (r = 0.57 and r = 0.52, P < 0.0001), whereas standard nuclear
      texture, a parameter of chromatin homogeneity, was inversely correlated with
      progression (r = -0.80, P < 0.0001). The nuclear parameters were strongly
      interrelated (P < 0.0005). In multivariate analysis, the nuclear parameters were
      predominantly associated with adenoma-carcinoma progression (P < or = 0.0001) and
      were not influenced significantly by the individual molecular genetic
      alterations. Nuclear texture, however, was inversely correlated with fractional
      allelic loss, a global measure of genetic changes, in carcinomas (r = -0.39, P =
      0.011). The findings indicate that nuclear morphology in colorectal neoplasms is
      strongly related to tumor progression. Nuclear morphology and biologic behavior
      appear to be influenced by accumulated alterations in cancer-associated genes.

PMID- 1357974
TI  - Thrombomodulin expression in malignant pleural mesothelioma and pulmonary
      adenocarcinoma.
AB  - Thrombomodulin (TM) is a glycoprotein of molecular weight 75,000 kd that is
      normally present in restricted numbers of cells, including endothelial and
      mesothelial cells. In this study, the authors tested the possibility of using
      anti-TM to facilitate the diagnosis of mesothelioma. All of the 31 mesotheliomas
      and the two mesothelioma cell lines (MS-1 and MS-2) tested were stained
      positively with anti-TM. The specificity of anti-TM staining in mesothelioma
      cells was further confirmed by in situ hybridization of MS-1 cells with a TM
      specific probe. The expression of TM in MS-1 cells was increased markedly when
      these cells were induced by 12-0-tetradecanyl phorbol 13-acetate (TPA) to
      differentiate. The expression of TM in mesothelioma cells, however, did not
      correlate with any particular phase of the cell cycle. In an attempt to
      differentiate pleural mesothelioma from pulmonary adenocarcinoma, the authors
      compared the expression of TM, carcinoembryonic antigen (CEA), and Leu M1 in
      these two types of tumors. Only four of 48 (8%) pulmonary adenocarcinomas were
      stained positively by antibodies to TM. Therefore, immunohistochemical staining
      with antibodies to TM yielded 100% sensitivity and 92% specificity for diagnosis
      of mesothelioma. All of the mesotheliomas stained negatively for CEA and Leu M1,
      except for one, which showed minimal focal positivity for Leu M1. In contrast,
      79% and 60% of adenocarcinomas stained positively for CEA and Leu M1,
      respectively. These findings suggest that immunocytochemical staining with anti
      TM should be added to the battery of tests to increase the diagnostic sensitivity
      and specificity for differentiating mesothelioma from pulmonary adenocarcinoma.

PMID- 1357975
TI  - On the determination of turnover in vivo with tracers.
AB  - Theoretical and practical aspects of the application of tracer methods for the
      measurement of turnover of blood-borne compounds are discussed, with special
      regard to lactate. The validity of the application of the tracer into the aortic
      arch and sampling from the right atrium (A-V), the administration of tracer into
      the vena cava and sampling from the aorta (V-A), and sampling to the
      determination of turnover are examined, using numerical examples. It is shown
      that the difference between specific activity in arterial and mixed venous blood
      depends mainly on the cardiac output, the ratio of tracee turnover to the mass of
      circulating tracee, and the sites of production and utilization of the tracee.
      Conditions are shown under which the A-V and V-A modes overestimate or
      underestimate the true rate of turnover. In theory, the A-V mode provides an
      exact estimate of turnover when the mean specific activity of the tracee in the
      whole body equals the specific activity of mixed venous blood in the right heart.
      It is shown that, for compounds with a high turnover rate, the underestimate in
      the A-V mode is small, and the mode provides a close approximation of true
      turnover. The underestimate in the V-A mode at high turnover rates is extensive.
      Experimental evidence indicates that, in several animal species, the specific
      activity of lactate and several amino acids in several organs and tissues nearly
      equals that in the venous blood, with the A-V mode providing a close
      approximation of the true turnover for these compounds.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1357976
TI  - Cholecystokinin inhibits gastric acid secretion through type "A" cholecystokinin
      receptors and somatostatin in rats.
AB  - The purpose of this study was to determine whether selective antagonism of type
      "A" cholecystokinin (CCK) receptors blocks inhibition of gastric acid secretion
      produced by CCK and whether this inhibition is mediated through either a
      somatostatin-dependent pathway or a vago-vagal reflex. Intravenous infusion of
      CCK (0.04-10 nmol.kg-1.h-1) dose dependently inhibited pentagastrin-stimulated
      gastric acid secretion in urethan-anesthetized rats, with a 50% inhibitory dose
      of 0.9 nmol.kg-1.h-1 and a maximum inhibition of approximately 50%. Blockade of
      type A CCK receptors using the selective type A receptor antagonist MK-329
      completely reversed the inhibitory effect produced by a maximal dose (4 nmol.kg
      1.h-1) of CCK. Immunoneutralization of endogenous somatostatin by administration
      of somatostatin monoclonal antibody abolished the inhibition produced by CCK.
      Concentrations of somatostatin in portal venous plasma were significantly
      increased after CCK administration; the increase in somatostatin was blocked by
      pretreatment with MK-329. In contrast, CCK-induced inhibition of gastric acid
      secretion was unaltered after perivagal capsaicin treatment. These results
      indicate that CCK inhibits gastric acid secretion in rats by activation of type A
      CCK receptors and through release of endogenous somatostatin.

PMID- 1357977
TI  - Ascending contraction mediated by 5-hydroxytryptamine3 receptors in canine small
      intestine.
AB  - We investigated the mechanism of ascending contraction induced by activation of 5
      hydroxytryptamine3 (5-HT3) receptors in anesthetized dogs. Pressure-measuring
      balloons were inserted into a loop of extrinsically denervated jejunum. Drugs
      were administered via the arterial tree to the oral or the anal segment and the
      ensuing mechanical responses were monitored. Administration of 2-methyl-5-HT (440
      pmol-44 nmol) to the anal segment caused contractions in the oral segment in a
      dose-dependent manner. This response was inhibited by treating the anal segment
      with ICS 205-930, cocaine, hexamethonium, or tetrodotoxin and by treating the
      oral segment with atropine or hexamethonium. The response persisted even after
      abolition of contraction in the anal segment by nifedipine. These results imply
      that activation of 5-HT3 receptors can induce an ascending contraction through an
      enteric excitatory pathway formed by a series of cholinergic interneurons and
      final cholinergic motor neurons, apart from the anal contraction.

PMID- 1357978
TI  - Chronic hypoxia impairs soluble guanylyl cyclase-mediated pulmonary arterial
      relaxation in the rat.
AB  - We have examined the effects of exposing rats to hypoxia (10% fractional inspired
      O2 concentration) for 2 and 7 days on endothelium-dependent and -independent
      vasodilation and also on the ability of guanosine 3',5'-cyclic monophosphate
      (cGMP) to activate cGMP-dependent protein kinase (G-kinase) in rat conduit
      pulmonary arteries (PA). The ability of acetylcholine (ACh) and sodium
      nitroprusside (SNP) to both relax PA rings and elevate tissue cGMP levels was
      significantly attenuated in PA from hypoxic animals. The ability of atrial
      natriuretic peptide to relax and generate cGMP in PA rings was unchanged by
      hypoxia. Relaxation and elevation of cGMP levels induced by SNP in aortic rings
      was unaltered by hypoxia. Similarly, hypoxia did not alter the concentration
      dependent activation by exogenous cGMP of G-kinase. We conclude that chronic
      exposure of rats to hypoxia results in a selective impairment of soluble guanylyl
      cyclase in rat PA, leading to an attenuation of ACh- and SNP-induced cGMP
      accumulation and relaxation.

PMID- 1357979
TI  - Localization, synthetic regulation, and biology of renal atriopeptin-like
      prohormone.
AB  - We recently demonstrated the synthesis and secretion of an atriopeptin (AP)-like
      prohormone in rat neonatal and adult cortical kidney cell cultures. However,
      these cultures contained proximal as well as distal tubular epithelial cells;
      thus characterization of the peptide synthetic cell was not possible. Also, by
      immunohistochemical techniques, we localized this AP-like prohormone to the
      distal cortical nephron in adult rat kidney. In this study, we examined further
      details of the kidney cortical cell type that expresses and secretes this AP-like
      peptide in adult renal cortical cell cultures, its regulation by adenylate
      cyclase via adenosine 3',5'-cyclic monophosphate (cAMP) generation, and its
      ability to stimulate guanylate cyclase. Tubular fragments were derived from
      cortical tissue of adult Sprague-Dawley rats and separated into four fractions on
      Percoll density gradient. Cell cultures generated from fraction 3 secreted 5- to
      10-fold the amount of this renal peptide compared with fractions 2 and 4. Further
      cell culture characterization was performed by agonist-stimulated cAMP formation,
      kallikrein localization, and prostaglandin E2 formation. From these analyses, it
      was determined that tissue band 3 was enriched for distal cortical connecting
      tubules. To further evaluate whether mammalian distal nephron synthesizes an AP
      like protein, we determined that two immortalized mouse cell lines, derived from
      either the distal convoluted tubule or cortical collecting tubule, synthesized a
      radiolabeled AP after being pulsed with [35S]-methionine.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1357980
TI  - CGRP and somatostatin modulate chronic hypoxic pulmonary hypertension.
AB  - Chronic hypoxic pulmonary hypertension (PH), associated with increased pulmonary
      arterial pressure (PPA) and right ventricular hypertrophy (RVH), correlates
      significantly with calcitonin gene-related peptide (CGRP) and somatostatin (SOM)
      levels in lung and blood. CGRP's role in regulation of PPA in chronic hypoxia and
      its potential interactions with SOM were investigated. CGRP, its antibody (ab)
      and blocker, CGRP-(8-37), SOM-14, SOM-28, and SOM-ab, respectively, were infused
      into the pulmonary circulation of hypobaric hypoxia rats for 4, 8, and 16 days.
      Thereafter, under pentobarbital sodium anesthesia, PPA was measured in the right
      ventricle and main pulmonary artery. Chronic CGRP infusion prevented PH at all
      times, whereas immunoneutralization and receptor blocking exacerbated PH. SOM-28
      also exacerbated while SOM-14 and SOM-ab decreased PH. RVH generally reflected
      the PPA. Radioimmunoassay confirmed successful infusion of the peptides with
      negligible peptide degradation in the pumps throughout 16 days and showed
      complete immunoneutralization of CGRP with its ab. Peptide levels in lung tissue
      suggest inhibition of CGRP release by SOM-28 and increased plasma SOM with CGRP
      infusion. In vitro pharmacological studies suggest that CGRP exerts a receptor
      mediated nonadrenergic, nonmuscarinic vasodilatory effect in the lung which is
      independent of endothelium-derived relaxing factor and does not involve ATP
      dependent potassium channels. We conclude that endogenous CGRP plays an important
      role in pulmonary pressure homeostasis during hypoxia, by directly dilating
      pulmonary vasculature, thus ameliorating the development of chronic hypoxic
      pulmonary hypertension in rats.

PMID- 1357981
TI  - Contractile actions of C5a on isolated porcine myocardium.
AB  - Although intracoronary administration of the complement component, C5a, produces
      deleterious effects on regional coronary blood flow and segmental ventricular
      function, it is unclear whether a direct myocardial action contributes to the
      dysfunction induced by the anaphylatoxin. We therefore evaluated the effects of
      purified porcine C5a on contractile tension of isolated supported ventricular
      trabeculae from pig hearts. Muscles were studied in a myograph bath at 30 degrees
      C, electrically stimulated 12 times per minute, and stretched to produce maximal
      isometric developed tension. C5a concentrations of 30, 100, and 300 ng/ml
      increased tension (P less than 0.05) 9.8, 5.5, and 20.9%, respectively. In seven
      of nine muscles exposed to 300 ng/ml C5a, tension initially decreased 10.5% (P
      less than 0.05) before the positive inotropic effect. Tachyphylaxis was
      demonstrated by lack of contractile response to a second administration of C5a
      greater than 70 min after the initial exposure to the complement fragment.
      Blockade of histamine H1 receptors with diphenhydramine (10(-6) M) markedly
      attenuated both the positive and negative contractile responses to C5a. beta
      Adrenoceptor blockade with propranolol (5.6 x 10(-7) M) did not alter the
      response to C5a. Levels of thromboxane (Tx)B2, the stable metabolite of TxA2,
      were augmented in the bath after exposure to C5a (59 +/- 27.3 to 104 +/- 28.2
      pg/ml, P less than 0.05). Although the TxA2 agonist, U-46619 (50 ng/ml),
      significantly increased tension, TxA2 receptor blockade with SQ 29548 (50 ng/ml)
      did not alter the response to C5a.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1357982
TI  - Parasympathetic involvement in rapid meal-associated conditioned insulin
      secretion in the rat.
AB  - Blood glucose and plasma insulin concentrations were measured in blood sampled
      via a cardiac catheter in freely moving rats. To obtain a rapid conditioned
      cephalic phase of insulin secretion, rats were habituated to one of two feeding
      schedules. Clock-activated opening of doors in front of the food hopper imposed a
      feeding schedule of either six meals per day or two meals per day. When the doors
      were opened in both conditions, insulin increased rapidly during the first minute
      of feeding in the middle of the light phase. However, when presented an empty
      food hopper immediately after door opening, only rats in the two meal per day
      condition showed raised insulin levels and not rats in the six meal per day
      condition. This response was abolished following pharmacological blockade of
      nicotinic receptors with hexamethonium and muscarinic receptors with atropine.
      The present study shows that rapid conditioned insulin secretion can be evoked
      within one minute by a meal-associated stimulus. These results further indicate
      that this conditioned insulin secretion is vagally mediated and that its
      occurrence is dependent on the nature of the feeding schedule.

PMID- 1357983
TI  - Ontogeny of DA1 receptor-mediated natriuresis in the rat: in vivo and in vitro
      correlations.
AB  - The natriuretic and diuretic effects of dopamine are attenuated in the young.
      Because dopamine has actions on receptors (e.g., adrenergic, serotonin) other
      than dopamine, we studied a novel dopamine agonist, pramipexole, which has a
      selectivity to both DA1 and DA2-receptor subtypes. Intravenous administration of
      pramipexole resulted in a dose-related (1, 10, and 100 micrograms.kg-1.min-1)
      increase in urine flow and absolute and fractional sodium excretion and a
      decrease in mean arterial pressure (MAP) in three groups of rats studied.
      Pramipexole induced a greater decrease in MAP in 6- to 7- (n = 5) and 9- to 16-
      (n = 6) than in 3- to 4-wk-old (n = 8) rats; the natriuresis and diuresis were
      greatest in 12- to 16- and least in 3- to 4-wk-old rats. The renal effects of
      pramipexole were mainly due to actions at the DA1 receptor, since these effects
      were completely blocked by the coinfusion of a DA1 antagonist, SKF 83742. To
      explore further a cause of the attenuated natriuretic effect of pramipexole in
      the young, we studied the effect of a selective DA1-receptor agonist, fenoldopam,
      on amiloride-sensitive 22Na+ uptake in renal brush-border membrane vesicles. The
      3-s amiloride-sensitive uptake was inhibited (45%) by fenoldopam (5 x 10(-5)M) in
      9- to 16- (n = 6) but not in 3- to 4-wk-old (n = 5) rats. These studies suggest
      that the attenuated natriuretic effect of dopamine in the young is in part due to
      decreased DA1 action on the brush-border membrane Na(+)-H+ exchanger.

PMID- 1357984
TI  - Somnogenic, pyrogenic, and anorectic activities of tumor necrosis factor-alpha
      and TNF-alpha fragments.
AB  - Exogenously administered tumor necrosis factor-alpha (TNF-alpha) elicits several
      symptoms of generalized infections such as fever, increased sleep, and anorexia.
      The aim of the present work was to localize these effects of TNF-alpha to
      specific amino acid sequences of the parent molecule by characterizing the in
      vivo and in vitro activities of several synthetic TNF-alpha fragments.
      Intracerebroventricular injection of TNF-alpha elicited dose-dependent fevers and
      increases in non-rapid-eye-movement sleep (NREMS) in rabbits. Four fragments also
      promoted NREMS and five elicited monophasic fevers. All of the somnogenic
      fragments share the amino acid sequence 31-36. In rats, TNF-alpha and one of the
      fragments [TNF-alpha-(69-100)] suppressed 12-h food intake. Furthermore, TNF
      alpha increased the expression of the intercellular adhesion molecule-1 and
      enhanced interferon-gamma-induced HLA-DR expression in human glioblastoma cell
      line. In contrast, none of the fragments possessed these in vitro activities. Our
      in vivo results support the concept that there are biologically active regions in
      the TNF-alpha molecule.

PMID- 1357985
TI  - Induction of ICAM-1 by TNF-alpha, IL-1 beta, and LPS in human endothelial cells
      after downregulation of PKC.
AB  - The intercellular adhesion molecule 1 (ICAM-1) is induced on endothelial cells by
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and
      lipopolysaccharide (LPS). We have reported the sensitivity of cytokine-induced
      ICAM-1 expression to protein kinase inhibitors, including inhibitors of protein
      kinase C (PKC) [C. L. Myers, S. N. Desai, J. Schembri-King, G. L. Letts, and R.
      W. Wallace. Am. J. Physiol. 262 (Cell Physiol. 31): C365-C373, 1992]. To directly
      investigate the role of PKC in ICAM-1 induction, we downregulated PKC by
      pretreatment of human umbilical vein endothelial cells with phorbol 12-myristate
      13-acetate (PMA) and assessed ICAM-1 protein and mRNA induction elicited by
      subsequent exposure to inflammatory stimuli. PMA treatment results in ICAM-1
      protein induction that declines to basal levels by 3 days. Western blots of
      endothelial cell lysates reveal a nearly complete loss of immunologically
      reactive PKC. Subsequent activation with cytokine or LPS leads to reinduction of
      ICAM-1 protein and mRNA; however, the cells no longer produced substantial
      amounts of ICAM-1 protein or mRNA in response to PMA stimulation. Cross
      desensitization is observed with phorbol dibutyrate, while 4 alpha-phorbol has no
      desensitizing effect. The data indicate that PKC activation, while capable of
      inducing ICAM-1 expression, is not essential for ICAM-1 induction by the
      inflammatory mediators TNF-alpha, IL-1 beta, or LPS.

PMID- 1357986
TI  - Expression of aminopeptidase N in fetal rat lung during development.
AB  - The ectopeptidase, aminopeptidase N, serves as a cell surface marker of the
      apical surface of the alveolar type II epithelial cell in adult lung. It is also
      present in fetal lung before differentiation of morphologically mature type II
      alveolar epithelial cells, suggesting that it is expressed by precursors of the
      type II cells. We have examined the mRNA coding for the aminopeptidase in adult
      and fetal lung and in mature type II cells and determined levels of mRNA and
      immunoreactive protein during fetal lung development. Comparison of the temporal
      patterns of steady-state levels of aminopeptidase mRNA and immunoreactive protein
      during development show that the expression of the protein is developmentally
      regulated and that expression is regulated, at least in part, at a
      pretranslational level. Both mRNA and immunoreactive protein levels increase
      severalfold on the final gestational day, suggesting that the function of the
      aminopeptidase may be associated with air breathing.

PMID- 1357988
TI  - Age-dependent changes in alpha-adrenoceptor-mediated contractility of isolated
      human resistance arteries.
AB  - Human subcutaneous resistance arteries (122-298 microns), isolated from 139
      patients undergoing surgery, were mounted in an isometric myograph. With the use
      of multiple regression analysis, five different modes of activation were examined
      for possible associations with age and mean arterial blood pressure of the
      patients: the contractile responses to 10 microM norepinephrine (mixed alpha 1
      agonist/alpha 2-agonist), perivascular nerve stimulation, 10 microM phenylephrine
      (alpha 1-agonist), 100 microM B-HT 933 (alpha 2-agonist), and depolarization by
      potassium chloride. Blood pressure increased significantly with age. Blood
      pressure independently was not correlated to any mode of activation. With
      increasing patient age, however, responses to norepinephrine, phenylephrine, and
      perivascular nerve stimulation decreased, whereas the response to B-HT 933
      increased; responses to potassium chloride were unaltered. Also corrected for
      changes in blood pressure, age independently was negatively correlated to the
      response to norepinephrine and phenylephrine, whereas a positive, though
      nonsignificant (P value = 0.12), correlation was observed between age
      independently and the response to B-HT 933. These data suggest that the ability
      of isolated human resistance arteries to evoke contractions medicated by
      postjunctional alpha 1-, but not alpha 2-adrenoceptors, decreases with age.

PMID- 1357987
TI  - Cyclosporin and quinidine inhibition of renal digoxin excretion: evidence for
      luminal secretion of digoxin.
AB  - We studied the in vivo luminal and contraluminal uptake of [3H]digoxin in dog
      kidney using the single-pass multiple indicator dilution method. A bolus tracer
      of 125I-albumin (plasma reference), creatinine, or L-[14C]glucose [extracellular
      reference (ecf)] and [3H]digoxin (or [3H]ouabain) was injected into the left
      renal artery, and timed serial samples were collected from the left renal vein
      (basolateral uptake) and left and right ureters (luminal uptake). [3H]ouabain was
      excreted solely by filtration and exhibited saturable and irreversible binding at
      the basolateral surface. Uptake of [3H]digoxin across the basolateral membrane
      was large and nonsaturable. Despite urine flow-dependent reabsorption and
      approximately 20% protein binding, the urine recovery ratio for [3H]
      digoxin/glomerular (ecf) marker was 0.97 +/- 0.04 (n = 29), indicating net
      digoxin secretion. After intravenous infusions of cyclosporin in Cremophor EL
      (0.5-3.5 microM), the urine recovery ratio decreased in a dose-dependent manner
      from control values of 1.13 +/- 0.06 (n = 12) to 0.62 +/- 0.03 (n = 14). There
      was no change in the relative renal vein recovery. Left renal artery infusion of
      quinidine (37.5 micrograms.min-1.kg-1) decreased the relative urine recovery of
      [3H]digoxin by 46% (n = 6) but had no effect on postglomerular extraction.
      Cyclosporin and quinidine are known inhibitors of P-glycoprotein. But digoxin did
      not compete with [3H]azidopine for binding in rat brush-border membranes or
      membranes prepared from the multidrug-resistant cell line CHRC5. The exact
      mechanism for renal digoxin secretion remains to be determined, but our results
      point to a luminal localization of this secretory system.

PMID- 1357989
TI  - Ontogeny of renal response to specific dopamine DA1-receptor stimulation in
      sheep.
AB  - The present study was designed to characterize the developmental changes in the
      renal responses to dopamine DA1-receptor activation in chronically instrumented
      preterm (109-115 days) and near-term (130-140 days, full term 145 days) fetal
      sheep. Cumulative doses of the selective DA1-agonist fenoldopam increased mean
      arterial blood pressure (MABP) in both preterm (+16 +/- 3%) and near-term fetuses
      (+16 +/- 3%) but had no significant effect on renal blood flow velocity. Infusion
      of the DA1-antagonist SCH-23390 did not affect the increase in MABP, suggesting
      that the effect of fenoldopam on MABP was not directly related to activation of
      DA1-receptors. Fenoldopam infusion had no significant effects on renal function
      parameters in preterm fetuses. In near-term fetuses, however, fenoldopam
      increased urinary flow rate (82.6 +/- 20.9%, P < 0.003), glomerular filtration
      rate (GFR; 16.6 +/- 4.9%, P < 0.01), urinary sodium excretion (40.1 +/- 14.9%, P
      < 0.02), and fractional excretion of sodium (26.8 +/- 11.2%, P < 0.03). Infusion
      of the DA1-antagonist SCH-23390 blocked the fenoldopam-induced diuresis and
      natriuresis but had no significant effect on the rise in GFR. Fenoldopam infusion
      had no significant effects on plasma renin activity and plasma aldosterone
      concentration and on urinary prostaglandin (PG) excretion (PGE2, PGF2 alpha, and
      6-keto-PGF1 alpha). Taken together, these results suggest that the renal effect
      of DA1-receptor activation is age dependent and that stimulation of DA1-receptor
      in near-term fetuses is associated with a diuresis and natriuresis that seem to
      be independent of renal hemodynamics and adrenal effects.

PMID- 1357990
TI  - Potentiation of thermoregulatory responses to isoproterenol by beta-adrenergic
      antagonists.
AB  - The thermoregulatory effects of isothermogenic doses of isoproterenol (Iso) and a
      novel beta-agonist (BRL 35135) were tested in rats at 22 degrees C and in rats
      trained to bar press for radiant heat at -8 degrees C. BRL 35135 produced
      hyperthermia at 22 degrees C and reduced operant responding for heat at -8
      degrees C, whereas Iso reduced body temperature and increased operant responding.
      In both situations, the negative effects of Iso on thermal balance were abolished
      by propranolol at doses that did not inhibit heat production. In anesthetized
      rats, propranolol potentiated the Iso-induced rise in brown adipose tissue and
      colonic temperature. The potentiation was more marked with the beta 2-selective
      antagonist ICI 118,551, whereas treatment with the beta 1-selective antagonist
      atenolol resulted in a profound Iso-induced reduction in temperature. The two
      selective antagonists also produced divergent responses in operant behavior in
      Iso-treated rats at -8 degrees C. These experiments demonstrate the extent to
      which responses to a nonselective agonist can be manipulated using appropriately
      low doses of selective antagonists and indicate that the effects of Iso on
      thermal balance are due to its beta 2 activity.

PMID- 1357991
TI  - Impact of psychiatric hospitalization on behavioral complications of Alzheimer's
      disease.
AB  - OBJECTIVE: The authors conducted a prospective study of the clinical utility of
      the four DSM-III-R subtypes of primary degenerative dementia of the Alzheimer
      type (with delirium, with delusions, with depression, or uncomplicated) and acute
      psychiatric hospitalization for treatment of these subtypes. METHOD: The subjects
      were 120 consecutive inpatients with Alzheimer's disease, most of whom had
      behavioral abnormalities. Each subject received detailed physical, neurological,
      psychiatric, and mental status examinations. The presence or absence of specific
      behavioral problems was also documented. Patients were treated with medication,
      psychotherapy, and behavioral techniques. RESULTS: While all patients could be
      assigned to one of the four DSM-III-R behavioral subtypes, the uncomplicated
      subtype did not accurately reflect the burden of behavioral symptoms in the
      patients who did not have delirium, delusions, or depression. Each behavioral
      subtype responded in a characteristic way to inpatient treatment, as reflected by
      changes in scores on four psychometric scales used to assess cognitive
      impairment, psychiatric symptoms severity, and level of functioning at admission
      and at discharge, as well as by changes in residential setting following
      hospitalization. Half of all patients admitted from their homes and two-thirds of
      those with depression were able to go home following discharge. CONCLUSIONS:
      Behavioral syndromes in Alzheimer's disease should not be overlooked, because
      they have both clinical and prognostic significance. Short-term psychiatric
      hospitalization is effective and efficient for achieving the goal of returning
      patients to their homes and for safely implementing specific treatments in this
      frail population, and it may reduce the need for institutionalization.

PMID- 1357993
TI  - Treatment of neuroleptic-resistant mania and schizoaffective disorders.

PMID- 1357992
TI  - A national study of psychiatrists' professional activities.
AB  - OBJECTIVE AND METHOD: A mail survey was conducted in 1988-1989 to study the
      professional activities of U.S. psychiatrists. Data from the 19,431 active
      respondents are reported. RESULTS: Nineteen percent of the psychiatrists were
      women, an increase from the 17% reported in 1982. The median age of the
      respondents was 50 years. Nearly one-third of the respondents expressed interest
      in each of the following areas of subspecialization: adolescent psychiatry,
      substance abuse, geriatrics, and consultation-liaison psychiatry. More than one
      fifth reported formal fellowship training in child/adolescent psychiatry. The
      psychiatrists worked an average of 48 hours per week--two-thirds in direct
      patient care--in an average of 2.3 different settings. The proportion of
      psychiatrists reporting private practice as their primary work setting showed a
      marked decline from 53% in 1982 to 45% in 1988. There was an increase from 4% in
      1982 to 11% in 1988 in those whose primary work setting was a private psychiatric
      hospital. The typical caseload was over 60 patients, with roughly half that
      number seen each week. For inpatients treated, the two most common diagnoses were
      affective disorders and schizophrenic disorders. In a typical week psychiatrists
      treated about one-half of their outpatients with individual psychotherapy; three
      fifths of these were also treated with medications. The average net income for
      psychiatrists working 35 hours or more per week was $99,850 for men and $73,174
      for women. CONCLUSIONS: Major trends evident from this study are
      subspecialization, medicalization, privatization, feminization, and
      organizational diversification.

PMID- 1357994
TI  - Stress fractures in ballet dancers.
AB  - We surveyed 54 female dancers in two professional ballet companies. A total of 27
      fractures were reported in 17 dancers. Metatarsal fractures were the most common
      (63%), followed by fractures of the tibia (22%) and spine (7%). Dancers who
      danced greater than 5 hours per day were significantly more likely to have a
      stress fracture than those dancing less than 5 hours per day. Dancers in the
      stress fracture group also had a significantly longer duration of amenorrhea than
      those in the group with no stress fractures. No significant difference was found
      between the dancers who had stress fractures and those who did not with regard to
      any of the other variables examined. These data suggest that prolonged
      amenorrheic intervals and heavy training schedules may predispose ballet dancers
      to stress fractures. Of the 17 dancers with stress fractures, only 1 had neither
      of these risk factors.

PMID- 1357995
TI  - Liver adenomatosis with granulomas in two patients on long-term oral
      contraceptives.
AB  - We report two cases of liver cell adenomatosis associated with granulomatous
      hepatitis, both developed in white women (52 and 39 years of age) on long-term
      oral contraceptives (for 18 and 12 years, respectively). The first patient
      underwent surgery for five hepatic tumors 1-7 cm in diameter; the other patient
      had a partial segmentectomy for a 4-cm hepatic nodule of the right lobe. In both
      cases, dissection of the liver showed many other diffuse and smaller nodules.
      Histologically, all tumors were benign liver cell adenomas, with cellular atypia
      in the largest tumor and associated in both cases with granulomatous hepatitis,
      with numerous noncaseating epithelioid and giant cell granulomas located either
      only in the tumors (case 1) or diffusely in the tumoral and nontumoral hepatic
      parenchyma (case 2). During follow-up, ultrasound showed new nodular lesions in
      case 2, whereas in case 1 evolution was uneventful. In estroprogestative
      associated liver diseases, adenomas are common, but adenomatosis and granulomas
      are rare. An association of these latter two conditions would seem to be
      exceptional. The prognosis for adenomatosis remains uncertain.

PMID- 1357996
TI  - Practicality of molecular studies to evaluate small lymphocytic proliferations in
      endoscopic gastric biopsies.
AB  - Fifteen endoscopic gastric biopsies (GBx) from 12 patients with small lymphocytic
      infiltrates morphologically raising a differential of indeterminate lymphocytic
      infiltrate versus mucosa-associated lymphoid tissue (MALT) lymphoma were analyzed
      genotypically after frozen-section identification of the abnormal lymphocytic
      infiltrate. Frozen-section immunoperoxidase immunophenotyping was equivocal in
      each case. All patients had abdominal pain attributable to superficial gastric
      ulceration, most often antral, without peripheral lymphadenopathy or
      hepatosplenomegaly. Rearrangement of the immunoglobulin heavy-chain gene (JH-R,
      seven patients) or kappa light-chain gene (JK-R, eight patients), was found in
      eight GBx from eight (seven stage IAE; one stage IBE) of 12 patients,
      establishing, in conjunction with the histologic features, a diagnosis of low
      grade B-cell lymphoma. This diagnosis had not been tenable on multiple prior GBx,
      ranging from one to five per patient, over intervals of 1 month to 6.5 years
      (median 4.5 months). The T-cell receptor beta-chain gene retained germline
      configuration in all cases. Insufficient DNA for molecular studies was extracted
      from the GBx of two patients, one with JK-R (JH-G) on subsequent GBx and one
      without further GBx. One patient had two GBx, each demonstrating a single
      additional band in HindIII digests hybridized with the JH probe. No
      rearrangements were detected in either the BamHI or the EcoRI digests. Uninvolved
      tissue from this patient was not available for the exclusion of restriction
      fragment length polymorphism. Three GBx (two patients) showed germline JH genes
      (JH-G). One had a partial gastrectomy (histology: MALT lymphoma) in 1981 followed
      by GBx in 1983 (histologically benign) and in 1990 (JH-G), and negative
      esophagogastroduodenoscopy (EGD) in 1991 without biopsy. The other patient (two
      GBx with JH-G) had multiple subsequent abnormal EGD, but no biopsies since
      December 18, 1990. Adequate DNA for gene rearrangement studies can be extracted
      from GBx samples weighing as little as 20 mg. The two samples with insufficient
      DNA weighed 1 and 16 mg, respectively. Practically speaking, the remainder of a
      frozen block from a single GBx is adequate, thus allowing the screening of
      multiple endoscopic GBx by sequential frozen sections to determine which one
      contains the most extensive lymphocytic infiltrate for molecular study.
      Consistent results are obtained on samples weighing 40 to 60 mg. This method is a
      suitable alternative to kappa/lambda frozen-section immunoperoxidase
      immunostaining, which can be uninterpretable on endoscopic biopsies or small
      biopsies from other sites.

PMID- 1357997
TI  - Prognostic significance of co-expression of c-erbB-2 oncoprotein and epidermal
      growth factor receptor in breast cancer patients.
AB  - The expression of c-erbB-2 oncoprotein and epidermal growth factor receptor
      (EGFR) was examined by immunocytochemical and radioreceptor assays in 115
      patients with primary breast cancer. In 48 of 115 patients (42%), the assays were
      found to be positive for the expression of c-erbB-2 oncoprotein, and, in 44 of
      115 (35%) patients, the assays were positive for the expression of EGFR. There
      was no correlation between the expression of c-erbB-2 oncoprotein and EGFR.
      Clinical survey demonstrated that both c-erbB-2 oncoprotein expression and EGFR
      expression have independent prognostic values. Furthermore, when patients were
      divided into three groups on the basis of the expression of both c-erbB-2
      oncoprotein and EGFR, those who were found to be positive for the expression of
      both c-erbB-2 oncoprotein and EGFR showed a worse prognosis than other groups.
      These results suggest that the combination of the expression of both c-erbB-2
      oncoprotein and EGFR may be important in selecting patients who have a poor
      prognosis.

PMID- 1357998
TI  - Treatment of adenocarcinoma of the pancreas with somatostatin and gonadoliberin
      (luteinizing hormone-releasing hormone). The French Associations for Surgical
      Research.
AB  - Experimental studies have shown a significant inhibition of adenocarcinoma of the
      pancreas by gonadoliberin (luteinizing hormone-releasing hormone [LH-RH]) and
      somatostatin. The aim of this prospective randomized study was to compare the
      potential value of somatostatin (250 micrograms every 8 hours), LH-RH (3.75 mg
      monthly), or combined, to a control group. One hundred sixty-three patients with
      adenocarcinoma of the pancreas who did not undergo resection for cure were
      divided into 4 groups that did not differ in terms of clinical, biologic, or
      pathologic data. The mean survival times were 6 months in the LH-RH plus
      somatostatin group, 5.5 months in the LH-RH group, 4.3 months in the control
      group, and 3.8 months in the somatostatin group. However, the life-table analyses
      for all randomized patients, and separately according to sex, the lymph node
      extension, and metastatic spread were not different between groups. Improvement
      of patient status was observed in 20% of the patients receiving hormone therapy
      without any difference noted between the treatment regimens. These disappointing
      results may be explained by the degree of extension of pancreatic carcinoma in
      the patients studied. The results suggest that different hormone therapy regimens
      might be considered according to the age and the sex of patients, as well as to
      the presence or absence of hormone receptors.

PMID- 1357999
TI  - Vecuronium: an anthropometric comparison.
AB  - This study set out to determine if there was any resistance to vecuronium in
      Nepalese studied in Nepal compared with Nepalese, Chinese and European patients
      studied in Hong Kong. The four groups, each of 10 male and 10 female patients,
      were intubated 60 s after administration of 0.1 mg.kg-1 vecuronium. The Nepalese
      patients in Nepal had significantly less satisfactory intubating conditions (p =
      0.002). Similarly, male patients had significantly less satisfactory conditions
      than female patients (p = 0.004). Some anthropometric measurements were
      significantly different between the patients in Nepal and those in Hong Kong.
      There were also sex-related anthropometric differences. It is suggested that
      differences in response to vecuronium could be explained by differences in
      distribution volume and muscle mass.

PMID- 1358000
TI  - Characterization of glucose microsensors for intracellular measurements.
AB  - Ultrasmall glucose sensors have been constructed by using platinum-deposited
      carbon ring microelectrodes with glucose oxidase. Response times as low as 270 ms
      have been obtained with these sensors. Moreover, there is a linear relationship
      between sensor tip diameter and response times. The use of these sensors has been
      demonstrated in the detection of glucose in single-cell cytoplasm of the large
      dopamine cell of the pond snail Planorbis corneus. Current responses obtained at
      these sensors implanted into a cell increase following injection of 2 pL of
      glucose solution (3 M) into the cell. Results obtained from these experiments
      show that these sensors are suitable for glucose monitoring in ultrasmall
      environments. In addition, characterizations of these sensors have been
      investigated under different O2 concentrations. At atmospheric oxygen
      concentrations, glucose levels in the submillimolar range can be measured without
      oxygen interference; however, oxygen interference can be substantial at low
      oxygen concentrations.

PMID- 1358001
TI  - Efficacy of anticholinergic and beta-adrenergic agonist treatment of maximal
      cholinergic bronchospasm in tracheally intubated rabbits.
AB  - Cholinergically induced bronchoconstriction is thought to be a major cause of
      bronchospasm during anesthesia. We used tracheally intubated rabbits (4-mm
      endotracheal tube) stimulated with methacholine to assess the efficacy of beta
      adrenergic agonist and anticholinergic treatment in reversing the increases in
      respiratory system resistance. Four groups were compared: (a) inhaled
      metaproterenol, 20 puffs via metered dose inhaler (0.65 mg/puff); (b) inhaled
      ipratropium bromide, 20 puffs from a metered dose inhaler (18 micrograms/puff);
      (c) 2 mg of intravenous atropine; and (d) no treatment after methacholine
      challenge as a control group. Methacholine increased respiratory system
      resistance from 0.041 +/- 0.001 (mean +/- SEM) to 0.098 +/- 0.006 cm H2O.mL-1.s-1
      (P < 0.001). Whereas beta-adrenergic agonist treatment was ineffective in
      ameliorating bronchoconstriction, inhaled ipratropium bromide and atropine were
      highly effective, causing an 86%-88% reversal in the methacholine-induced
      increase in respiratory system resistance. Both these agents were also effective
      in improving dynamic compliance. We conclude that inhaled ipratropium bromide is
      effective in treating cholinergic bronchospasm even when administered via a small
      endotracheal tube and that the beta-adrenergic agonist metaproterenol is
      ineffective in rabbits in the face of maximal cholinergic stimulation.

PMID- 1358002
TI  - Total intravenous anesthesia: effects of opioid versus hypnotic supplementation
      on autonomic responses and recovery.
AB  - During radical prostatectomy procedures under total intravenous anesthesia, acute
      hemodynamic responses to retropubic dissection (30% +/- 8% to 36% +/- 12% [mean
      +/- SD] increases in mean arterial pressure) were treated with supplemental doses
      of either an opioid analgesic (alfentanil) or a sedative-hypnotic (propofol) to
      return the mean arterial pressure to within 10% of the preincision value.
      Although both drugs were effective, control with propofol required 10.1 +/- 2.5
      min compared with 6.3 +/- 2.6 min in the alfentanil group (mean +/- SD; P <
      0.01). Plasma stress hormone concentrations increased significantly in response
      to this surgical stimulus: epinephrine increased from 246% +/- 169% to 283% +/-
      330%; norepinephrine increased from 44% +/- 33% to 83% +/- 104%; and antidiuretic
      hormone increased from 1300% +/- 1591% to 1700% +/- 1328%. Both alfentanil and
      propofol were equally effective in returning the catecholamine concentrations to
      their preincision levels. However, antidiuretic hormone levels remained above
      preincision values in both groups. Despite earlier awakening (3.4 +/- 2.9 vs 9.1
      +/- 6.8 min; P < 0.05) in the alfentanil treatment group, there was no difference
      in time to spontaneous ventilation or tracheal extubation between the groups. In
      addition, 36% of the alfentanil-treated patients required antihypertensive
      therapy in the postanesthesia care unit compared with only 9% in the propofol
      group (P < 0.05). Postanesthesia care unit and hospital discharge times were
      similar in both treatment groups. We conclude that supplemental doses of
      alfentanil or propofol were equally effective in controlling acute hemodynamic
      and hormonal responses to surgical stimuli during total intravenous anesthesia.

PMID- 1358004
TI  - Tetanus-induced changes in apparent recovery after bolus doses of atracurium or
      vecuronium.
AB  - The current study evaluated the duration and magnitude of post-tetanic effects in
      56 patients recovering from a bolus dose of nondepolarizing relaxant to assess
      the impact of tetanus on monitoring in a common clinical setting. After induction
      of general anesthesia (thiopental, fentanyl, oxygen, nitrous oxide, and
      isoflurane), a baseline response to train-of-four (TOF) stimulation was recorded
      using an adductor pollicis force transducer, and the ratio of the fourth response
      (T4) to the first (T1) was calculated. Patients then received a bolus dose of
      either atracurium 0.50 mg.kg-1 (n = 28) or vecuronium 0.10 mg.kg-1 (n = 28). TOF
      was recorded at 12-s intervals between 25% and 75% recovery of T1 (time25-75%,
      first data set); then, block was reestablished with the same agent (atracurium
      0.10 or vecuronium 0.02 mg.kg-1), and monitoring of time25-75% was repeated
      (second data set). Subjects were randomized such that none, one, or both sets had
      TOF monitoring interrupted by a 5-s, 50-Hz tetanic stimulus at 50% recovery
      (TET). For each drug, 7 patients were assigned to each of the four possible
      sequences: no tetanus (NOTET) set followed by NOTET set; NOTET-TET; TET-NOTET;
      and TET-TET. After either drug, the TET data sets demonstrated significant
      acceleration of recovery of T1 from 50% to 75% (time50-75%) of its baseline
      height (P less than 0.05 by paired t test). After atracurium, time50-75% was
      shortened by the tetanic stimulation from a control of 6.3 +/- 1.1 to 5.0 +/- 1.3
      min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358003
TI  - Defining the dose range for esmolol used in electroconvulsive therapy hemodynamic
      attenuation.
AB  - We evaluated the clinical effectiveness of esmolol, an ultra-short-acting, beta
      adrenergic receptor blocking drug, to control the sinus tachycardia and increase
      in arterial blood pressure induced by electroconvulsive therapy (ECT). Each of 20
      patients, ASA physical status I-III, participated in a double-blind, randomized
      Latin-Square study involving two matched-pair trials (placebo versus esmolol
      given as a 500-micrograms/kg bolus followed by either 300 micrograms.kg-1.min-1
      [high dose], 200 micrograms.kg-1.min-1 [medium dose], or 100 micrograms.kg-1.min
      1 [low dose] infusion of esmolol) during ECT. Each patient acted as his or her
      own control (total number of ECT procedures were 160). We administered a 1-min
      bolus of placebo (normal saline) or esmolol at the rate of 500 micrograms.kg
      1.min-1 followed by either high-, medium-, or low-dose esmolol or placebo for an
      additional 3 min. We then induced anesthesia with methohexital (1 mg/kg) and
      succinylcholine (0.5 mg/kg) IV. Ninety seconds after the administration of
      succinylcholine, the electrical stimulus was applied to induce seizure. The
      infusion of placebo or esmolol was discontinued 3 min after the electrical
      stimulus. Significant decreases were found in mean heart rate from minute 3 until
      minute 7 and in the maximum heart rate. The mean of each patient's maximum heart
      rate after seizure changed from 147 +/- 18 bpm in placebo patients to 112 +/- 20
      bpm in high-dose esmolol patients; to 121 +/- 23 bpm in medium-dose esmolol
      patients; and to 124 +/- 20 bpm in low-dose esmolol patients.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1358005
TI  - AMPA and NMDA receptor antagonists do not decrease hippocampal glutamate
      concentrations during transient global ischemia.
AB  - Increased extracellular concentrations of glutamate during episodes of cerebral
      ischemia may be due in part to a positive glutaminergic feedback loop. We
      evaluated the effect of selective AMPA or NMDA receptor antagonists on
      hippocampal extracellular concentrations of excitatory amino acids during
      ischemia and reperfusion. Thirteen New Zealand white rabbits were subjected to 10
      min of global cerebral ischemia produced by neck tourniquet inflation (20 psi)
      combined with systemic hypotension during halothane (1-1.5%) anesthesia.
      Hippocampal extracellular concentrations of glutamate, aspartate, and glycine
      were monitored using in vivo microdialysis. NBQX (a selective AMPA receptor
      antagonist), MK801 (a noncompetitive NMDA receptor antagonist), or 5% dextrose
      was administered starting 1 h before ischemia. The NBQX group (n = 4) received 5
      mg.kg-1 of NBQX intravenously (dissolved in 5% dextrose) over 5 min followed by
      an infusion of 5 mg.kg-1.h-1. The 5% dextrose group (n = 4) received an
      equivalent volume of 5% dextrose. The peak concentrations of glutamate,
      aspartate, and glycine in the early reperfusion period were 5-8-fold, 9-10-fold,
      and 4-5-fold higher than preischemic values, respectively. There were no
      significant differences, however, among the three groups in the concentrations of
      glutamate, aspartate, or glycine at any time during the study. These results do
      not support the existence of a positive feedback loop for glutamate mediated via
      AMPA or NMDA autoreceptors in the hippocampus during transient global ischemia or
      reperfusion.

PMID- 1358006
TI  - Maternal esmolol administration resulting in fetal distress and cesarean section
      in a term pregnancy.

PMID- 1358007
TI  - [The prevention of undesirable changes in the endocrine system in patients in the
      intraoperative period using stress-preventive preparations].
AB  - The functions of the adrenal cortex, thyroid gland and carbohydrate metabolism
      have been analysed in 20 patients to whom current schemes of premedication and
      anesthesia have been applied, 20 patients who in the nearest preoperative period
      and intraoperatively have been administered ganglioblockers and adrenolytics, and
      20 patients in whom clophelin has been used during premedication and anesthesia.
      It has been established that the use of stress-protecting agents for
      premedication and anesthesia almost prevents hyperergic reaction of the adrenal
      cortex, thyroid gland and carbohydrate metabolism.

PMID- 1358008
TI  - Sheep linkage mapping: restriction fragment length polymorphism detection with
      heterologous cDNA probes.
AB  - A selection of cattle, human and sheep cDNA probes were screened against sheep
      genomic DNA, cut with 10 different restriction enzymes, to assess the usefulness
      of these probes for restriction fragment length polymorphism (RFLP) linkage
      studies in sheep. Two-thirds of the cattle cDNA probes showed moderate to strong
      homology with sheep DNA samples, compared with less than half of the human cDNA
      probes at the final washing stringency chosen for the experiments. The set of
      probes tested detected a useful frequency of RFLPs. Fifty-seven per cent of
      probes showing moderate to strong homology identified RFLPs with one or more
      restriction enzymes. Restriction enzymes that detected RFLPs most frequently in
      sheep were TaqI and MspI. The results show that sheep and cattle cDNA probes,
      including candidate genes for production traits, identified a high frequency of
      RFLPs suitable for genetic mapping in sheep.

PMID- 1358010
TI  - An Eco RI restriction fragment length polymorphism at the ovine alpha S2-casein
      (CASAS2) locus.

PMID- 1358009
TI  - Detection of bovine alpha s1-casein genomic variants using the allele-specific
      polymerase chain reaction.
AB  - A method was developed to distinguish between genotypic variants B and C of
      bovine alpha s1-casein, using the allele-specific polymerase chain reaction
      (ASPCR). The alpha s1-casein genotype determined for 17 Jersey cows by the ASPCR
      method was confirmed by typing the alpha s1-casein milk proteins on isoelectric
      focusing gels. Using the ASPCR method described, rapid analysis of the alpha s1
      casein genotype of bulls is now possible. In addition, kappa-casein genotypes can
      be determined from the same PCR reaction.

PMID- 1358011
TI  - An Eco RI restriction fragment length polymorphism at the ovine locus for alpha 1
      type III collagen (COL3A1).

PMID- 1358012
TI  - New allelic fragment for the growth hormone-TaqI marker in cattle.

PMID- 1358013
TI  - TaqI reveals a polymorphism in sheep when probed with the ovine IgE gene.

PMID- 1358014
TI  - Biological properties and genetic analysis of the ompA locus in chlamydiae
      isolated from swine.
AB  - Eight strains of Chlamydia psittaci isolated from swine with pneumonia,
      pleuritis, pericarditis, and enteritis were characterized through analysis of the
      major outer membrane protein gene ompA by a two-step polymerase chain reaction,
      by their interactions with cells in culture, and by the morphologic features and
      ultrastructure of intracellular inclusions. Amplified chlamydial ompA DNA
      fragments were differentiated by restriction endonuclease digestion. Chlamydial
      isolates were separated into 2 types on the basis of ompA restriction fragment
      length polymorphism. Strains of type L71 had finely granular inclusions, whereas
      those of type 1710S contained pleomorphic reticulate bodies (RB) in the
      inclusions, which are characteristic of aberrant chlamydial developmental forms.
      Chlamydial types L71 and 1710S required centrifuge-assisted inoculation for
      efficient infection of cell cultures. Cultivation in cell culture medium
      containing cycloheximide increased the numbers of chlamydial inclusions about 1.5
      fold. These strains formed few elementary bodies in yolk sac cells of chicken
      embryos. Ultrastructurally, unique doublet RB were observed, particularly in
      strains of the ompA type L71. These doublets consisted of 2 RB, bounded by a
      cytoplasmic membrane, contained within a common cell wall and an extended
      periplasmic space. Ultrastructural examination of strains of the ompA type 1710S
      confirmed the aberrant chlamydial developmental forms, but evidence of viral
      infection of the RB as a cause of these aberrant forms was not found. The strain
      S45 isolated from intestinal sites of swine was a trachoma restriction fragment
      length polymorphism type. With the mouse biotype, it represented the second
      isolate from animals of Chlamydia trachomatis.

PMID- 1358015
TI  - Pathogenicity of porcine enterotoxigenic Escherichia coli that do not express
      K88, K99, F41, or 987P adhesins.
AB  - Three-week-old weaned and colostrum-deprived neonatal (less than 1 day old) pigs
      were inoculated to determine the pathogenicity of 2 enterotoxigenic Escherichia
      coli isolates that do not express K88, K99, F41, or 987P adhesins (strains 2134
      and 2171). Strains 2134 and 2171 were isolated from pigs that had diarrhea after
      weaning attributable to enterotoxigenic E coli infection. We found that both
      strains of E coli adhered in the ileum and caused diarrhea in pigs of both age
      groups. In control experiments, adherent bacteria were not seen in the ileum of
      pigs less than 1 day old or 3 weeks old that were noninoculated or inoculated
      with a nonpathogenic strain of E coli. These control pigs did not develop
      diarrhea. Antisera raised against strains 2134 and 2171 and absorbed with the
      autologous strain, grown at 18 C, were used for bacterial-agglutination and
      colony-immunoblot assays. Both absorbed antisera reacted with strains 2134 and
      2171, but not with strains that express K99, F41, or 987P adhesins. A cross
      reaction was observed with 2 wild-type K88 strains, but not with a K12 strain
      that expresses K88 pili. Indirect immunofluorescence with these absorbed antisera
      revealed adherent bacteria in frozen sections of ileum from pigs infected with
      either strain. We concluded that these strains are pathogenic and express a
      common surface antigen that may be a novel adhesin in E coli strains that cause
      diarrhea in weaned pigs.

PMID- 1358016
TI  - Modulation, in vivo and in vitro, of surface expression of CD18 by bovine
      neutrophils.
AB  - A series of experiments was designed to elucidate some of the factors that may
      influence surface expression of CD18 by bovine neutrophils. Expression of CD18
      was determined by immunofluorescence flow cytometry. Neutrophils recovered from
      the uterus of cows (n = 9) after intrauterine administration of sterile oyster
      glycogen solution expressed (mean +/- SD) 123 +/- 21% more CD18 than did
      circulating neutrophils recovered simultaneously from the same cows (P = 0.003).
      In 8 cows given 20 mg of dexamethasone IM daily for 3 days, expression of CD18 on
      blood neutrophils was 29.6 +/- 8% less after treatment than before treatment (P =
      0.0078). Neutrophils from 12 cows or bulls exposed to phorbol myristate acetate
      in vitro increased expression of CD18 by 137 +/- 37% (P = 0.0035). Likewise,
      exposure of neutrophils from 8 cattle to zymosan-activated bovine plasma
      increased CD18 exposure by 10.6 +/- 3.8% (P = 0.029). These findings indicate
      that expression of CD18 by bovine neutrophils is a dynamic system, capable of
      responding to inflammatory stimuli. Inadvertent activation of neutrophils may be
      responsible for some of the variance in expression observed when examining large
      groups of cattle for CD18 expression by neutrophils. The ability of bovine
      neutrophils to respond rapidly to various stimuli by increasing surface
      expression of CD18 indicates that a pool of intracellular CD18 may be available
      for inclusion in the plasmalemma, as has been reported for human neutrophils.

PMID- 1358017
TI  - [Inhalation therapy in the newborn].

PMID- 1358018
TI  - [Therapeutic advances in infantile asthma. New pharmacologic perspectives].

PMID- 1358019
TI  - [Molecular and cellular technics in the study of the expression of growth
      hormone].

PMID- 1358020
TI  - [Neuroregulation and the growth hormone].

PMID- 1358021
TI  - Biochemical Engineering VII. Conference proceedings. Santa Barbara, California,
      March 1991.

PMID- 1358022
TI  - Utility of magnetic resonance imaging in the detection of subdural empyema.

PMID- 1358023
TI  - Immunologic studies on the ear. Conference proceedings. Oita, Japan, October 8-9,
      1991.

PMID- 1358024
TI  - [Scientific workshop, Department of Animal Pathology INRA: the T lymphocyte in
      action: control of the immune response in animal pathology. November 26-27,
      1991].

PMID- 1358025
TI  - In vitro studies of the antirhinovirus activity of soluble intercellular adhesion
      molecule-1.
AB  - We studied the in vitro antirhinovirus activity of a soluble form of
      intercellular adhesion molecule-1 (sICAM-1). sICAM-1 inhibited the cytopathic
      effect of 10 representative human rhinovirus (HRV) serotypes of the major
      receptor group with, 50% effective concentrations (EC50s) of 0.1 to 7.9
      micrograms/ml. Cell type-dependent variation in the inhibitory activity of sICAM
      1 was observed for two major receptor group serotypes in HeLa cells (EC50,
      greater than 32 micrograms/ml), and no inhibitory effect was observed for two
      serotypes which use different cell receptors. Yield reduction assays showed that
      sICAM-1 inhibited the replication of HRV serotype 39 (HRV-39) in human adenoid
      explants in a concentration-dependent manner. No direct inactivation of
      infectivity of HRV-39 (EC50, 0.5 microgram/ml) was observed after incubation with
      sICAM-1 (32 micrograms/ml) for up to 24 h. Single-cycle-of-replication
      experiments with the addition of sICAM-1 at 10 micrograms/ml at different times
      showed that the inhibitory effect occurs only when sICAM-1 is added within 30 min
      after infection. In experiments in which absorption was carried out at 4 degrees
      C and then a single cycle of replication incubation was carried out at 33 degrees
      C, it was found that sICAM-1 at 10 micrograms/ml was inhibitory only when it was
      present during the absorption period. Our data show that sICAM-1 is inhibitory
      for representative major receptor group serotypes of HRV in two cell lines and
      human respiratory epithelium, that the interaction of sICAM-1 with HRV is readily
      reversible by dilution, and that the inhibitory effect of sICAM-1 on virus
      replication is present early in the infection cycle.

PMID- 1358026
TI  - Development of resistance to zidovudine in HIV strains isolated from CD4+
      lymphocytes and plasma during therapy.
AB  - An assay based on production of HIV antigen in cultures of CD4+ lymphocytes
      infected 'in vitro' with cell-free virus was established. Using this assay it was
      possible to isolate, propagate and reliably determine the zidovudine
      susceptibility of HIV isolates from all patients despite differences in cellular
      tropism and syncytium inducing capacity. Using this assay, differences in
      zidovudine susceptibility of 52 serial isolates obtained from 16 patients before
      and after initiation of therapy were examined. HIV with a 10- to 100-fold reduced
      susceptibility to zidovudine were isolated from 13 patients as early as 4 months
      after initiation of therapy. Number of months of zidovudine treatment was
      strongly associated with development of viral resistance, and high CD4 cell
      counts tended to be associated with lower rates of development of resistance.
      That patients can harbor mixtures of virus strains with different susceptibility
      to zidovudine was confirmed by the differences in susceptibility between isolates
      obtained simultaneously from CD4+ lymphocyte and plasma, and by the differences
      in susceptibility between virus strains isolated from clones of CD4+ lymphocytes.

PMID- 1358027
TI  - Regulation of urea uptake in Pseudomonas aeruginosa.
AB  - The energy-dependent urea permease was studied in two strains of Pseudomonas
      aeruginosa, measuring the uptake (transport and metabolism) of 14C-urea. In both
      strains urea uptake in vivo and urease activity in vitro differed significantly
      with respect to kinetic parameters, temperature and pH dependence and response to
      metabolic inhibitors. Ammonium strongly interfered both with the expression of
      the urea uptake system and its activity. The inhibition of the uptake activity by
      ammonium was partially relieved by hydraziniumsulfate, which prevented the
      translocation of ammonium into the cell, and in a methylammonium/ammonium
      transport-defective mutant of strain DSM 50071. Furthermore, methionine
      sulfoximine, which prevented the intracellular glutamine formation from ammonium
      via inhibition of glutamine synthetase, relieved the inhibition of urea uptake by
      ammonium. These findings suggested that urea uptake activity in P. aeruginosa is
      regulated by intracellular glutamine.

PMID- 1358028
TI  - Genomic studies on killer yeasts belonging to the genus Pichia.
AB  - Twenty-four species belonging to the genus Pichia were investigated using
      restriction fragment length polymorphism (RFLP) and Southern blot hybridization
      of their genomic DNA. Saccharomyces cerevisiae, Kluyveromyces lactis, Williopsis
      mrakii and Candida albicans were also included in this study. The RFLP patterns
      were obtained from digestion of yeast DNA with several restriction endonuclease
      enzymes, and showed various bands with different mobility; in most isolates, the
      more deeply stained bands were species-specific. This observation was confirmed
      by the results obtained from Southern blot hybridization of the EcoRI and XhoI
      RFLP patterns with P. anomala UCSC 25F DNA, digested with the same enzymes, used
      as probes. These bands are likely to be ribosomal DNA as shown by hybridization
      of digested DNA from unrelated yeast species (S. cerevisiae, K. lactis and C.
      albicans). However, one hybridized band, located at 3.9-4.1 Kb, seems to be
      peculiar to the Pichia species. Our study confirms the usefulness of molecular
      tools in studying genetic relatedness among yeasts.

PMID- 1358029
TI  - Insulin-mediated inhibition of the induction of tyrosine aminotransferase by
      dexamethasone.
AB  - Insulin-mediated regulation of glucocorticoid-induced expression of the liver
      specific gene tyrosine aminotransferase was studied in a clone of the Reuber rat
      hepatoma cells. Insulin inhibited dexamethasone-induced chloramphenicol
      acetyltransferase expression from approximately 4 kb of TAT 5' flanking sequence.
      The degree of this inhibition was comparable to the response of the endogenous
      gene. A construct of approximately 3 kbp of 5' flanking sequence exhibited no
      significant basal expression but retained sensitivity to glucocorticoids and to
      insulin inhibition of the glucocorticoid response. Results of further analysis of
      the insulin response in deletion constructs and constructs containing
      glucocorticoid responsive elements ligated to a heterologous promoter suggest
      that in addition to the glucocorticoid response elements a region close to the
      start site in the TAT promoter is necessary for insulin to inhibit glucocorticoid
      mediated induction of expression.

PMID- 1358031
TI  - [Genetic alterations in the genesis and development of ovarian cancer].
AB  - Genetic alterations of various cancers have been clarified by recent development
      of molecular biology. Multiple genetic alterations occur through the development
      of cancer. Both activation of proto-oncogenes and inactivation of tumor
      suppressor genes are important for the development of cancer. Alterations of
      oncogenes such as K-ras, c-erbB-2/HER-2/neu and c-myc, and those of tumor
      suppressor genes such as p53, RB and DCC have been reported in ovarian cancer.
      Allelic losses of the specific chromosomes, which suggest the existence of tumor
      suppressor genes on those chromosomes, also have been reported in ovarian cancer.
      Further studies on genetic alterations of ovarian cancer will clarify the
      mechanisms for the development of ovarian cancer and also will develop new
      methods for prevention, diagnosis and treatment in clinical.

PMID- 1358030
TI  - (6R)-5,6,7,8-tetrahydro-L-biopterin modulates nitric oxide-associated soluble
      guanylate cyclase activity in the rat cerebellum.
AB  - (6R)-5,6,7,8-Tetrahydro-L-biopterin (R-THBP) is a cofactor not only for aromatic
      amino acid hydroxylases in mammalian tissues but also for nitric oxide synthase
      (NOS) induced by endotoxins or cytokines in some kinds of cells. Recently it has
      been reported that nitric oxide (NO) has biological activity in endothelium and
      in brain as well. NO activates soluble guanylate cyclase (sGC). Superoxide reacts
      with NO easily and shortens the half-life of NO actions. We found, in a study
      using rat cerebellar cytosol fraction, that R-THBP itself did not directly
      activate sGC, but activated sGC at concentrations ranging from 0.1 to 10 microM
      only under NO generating conditions of activated NOS and in the presence of
      sodium nitroprusside. In addition, R-THBP (1 microM) did not alter the NOS
      activity, which was determined by L-citrulline formation. These results suggest
      that R-THBP may regulate sGC activity associated with NO formation in the central
      nervous system.

PMID- 1358032
TI  - [Treatment of recurrent ovarian cancer].
AB  - Significant prolongation of survival time among the patients with advanced
      ovarian cancer has been brought under the development of surgery and
      chemotherapy, but even those with clinical remission shows sometimes recurrence.
      For the recurrent ovarian cancer patients at present there are no definite
      strategy to treat the recurrent cases. Under these circumstance, we have reviewed
      the current treatment of cytoreductive surgery and chemotherapy for the recurrent
      cases. 1) surgical treatment Generally, in the cases of recurrent ovarian cancer,
      cytoreductive surgery is required to minimize the residual tumour in the abdomen.
      But sometimes we can find the distant metastasis including liver, lung, and lymph
      node. This means that surgery is not sufficient for control of recurrent tumor.
      Further adjuvant chemotherapy will be required to control metastatic tumors. 2)
      chemotherapy After the detail assessment of the initial treatment of cases, at
      first we should think about retreatment with CDDP-based regimen and secondly
      about dose-intensification of CDDP or CBDCA for the CDDP-resistant cases. And as
      combination regimens, topoisomerase inhibitors, etoposide or CPT-11 are also
      preferable to use, alkylating agents such as ifosfamide, 5-fluorouracil, and some
      current trials with new drug, taxol are effective for recurrent cases. In
      conclusion, further active chemotherapy using platinum compounds, topoisomerase
      inhibitors, taxol will be achieved for the control of the recurrent cases of
      ovarian cancer.

PMID- 1358033
TI  - Accidental ingestion of 'Ecstasy' (3,4-methylenedioxymethylamphetamine).
AB  - There is no report of the effects of 'Ecstasy' (3,4
      methylenedioxymethylamphetamine) poisoning in childhood. The case of a 13 month
      old boy who ingested one capsule of Ecstasy is reported. Neurological and
      cardiovascular side effects predominated, which responded well to treatment with
      a chlormethiazole infusion.

PMID- 1358034
TI  - Incidence of hereditary porphyria cutanea tarda (PCT) in a sample of the Italian
      population.
AB  - The determination of the enzymatic activity of URO-D in erythrocytes is the
      screening method used for differentiation between hereditary and non-hereditary
      forms of porphyria cutanea tarda (PCT). The aim of the present work was to
      establish the relative frequencies of the symptomatic and hereditary forms by the
      determination of the URO-D enzyme in the PCT patients who were regularly treated
      at the Centre for Porphyrins in our Institute. In the course of this work we also
      examined the statistical properties of the distributions of both normal and
      porphyric subjects, so as to be able to suggest values for discriminating between
      normal subjects and the various types of porphyric subjects.

PMID- 1358035
TI  - Induction of ICAM-1 expression by epidermal keratinocytes via a paracrine pathway
      possibly involving dermal dendritic cells.

PMID- 1358036
TI  - [Laser lithotripsy in the treatment of ureteral lithiasis].
AB  - Laser lithotripsy constitutes a safe method with a success rate of 95% in the
      treatment of ureteral calculi. The photoacoustic properties of the laser permit
      stone fragmentation without injury to tissue. The major disadvantage of this
      technique is its cost. The availability of increasingly smaller electrohydraulic
      systems that are less costly questions the routine use of the laser system.
      Another aspect that must be considered is the rapid development of endourologic
      techniques and instruments in recent years. The use of laser-induced shock waves
      is not exclusive to the field of Urology. In other surgical specialties where
      electrohydraulic energy is difficult to use, it constitutes a necessary
      technique. Such is the case of endoscopy of the bile ducts, fragmentation of
      pancreatic calculi and lithiasis of the salivary glands. Another possible field
      of application of laser-induced shock waves is coronary angioplasty.

PMID- 1358037
TI  - Circulating cytokine levels in patients with rheumatoid arthritis: results of a
      double blind trial with sulphasalazine.
AB  - Interleukin 1 (IL-1), IL-6, and tumour necrosis factor (TNF) alpha are
      pleiotropic cytokines produced predominantly by macrophages which have been
      implicated in the pathogenesis of rheumatoid arthritis (RA). Sulphasalazine has
      been shown to have disease modifying properties and to inhibit the production of
      cytokines in vitro. To evaluate the effect of sulphasalazine on cytokine
      production in vivo, serum cytokine levels were measured in a group of patients
      with RA entered into a randomised controlled trial. Serum levels of IL-1 alpha,
      IL-1 beta, IL-6, and TNF alpha were measured at baseline and at two monthly
      intervals for six months in 17 patients receiving sulphasalazine and in 22
      patients treated with placebo. The two groups of patients had a similar age and
      sex distribution, had had RA for less than a year, had no joint erosions, and had
      not been treated previously with any other disease modifying drugs. In the 39
      patients studied IL-1 alpha was detected (> 0.1 ng/ml) at baseline in 14 patients
      (median 0.24 ng/ml), IL-1 beta in 25 patients (median 1.0 ng/ml), TNF alpha in 27
      patients (median 1.2 ng/ml), and IL-6 in 33 patients (median 0.44 ng/ml). In the
      group treated with sulphasalazine there was a progressive and significant decline
      in serum IL-1 alpha, IL-1 beta, and TNF alpha levels over the six month period
      (median levels at six months were < 0.1, 0.12, and 0.44 ng/ml respectively).
      Interleukin 6 levels were significantly reduced only at the four month time point
      (median level of 0.23 ng/ml). These reductions were associated with improvements
      in clinical and laboratory measures of disease activity. In contrast patients
      receiving the placebo showed no changes in serum cytokine levels and no
      improvement in clinical and laboratory indices of disease activity. These results
      suggest that sulphasalazine may exert its disease modifying effect partly by
      suppressing cytokine production in vivo.

PMID- 1358038
TI  - Evaluation of sulphasalazine in the treatment of spondyloarthropathies.
AB  - Sulphasalazine has been shown to have an effect in patients with
      spondyloarthropathies, but the clinical indication for its use is controversial
      and its long term effect has not yet been evaluated. Treatment with
      sulphasalazine was analysed retrospectively in a group of 372 patients with a
      wide range of spondyloarthropathies to determine subsets of patients showing
      differential effects of the drug. One hundred and one patients received
      sulphasalazine at a mean daily dose of 2 g (ankylosing spondylitis, 54 patients;
      psoriatic arthritis, 21 patients; reactive arthritis, four patients; arthritis
      related to inflammatory bowel disease, six patients; undifferentiated
      spondyloarthropathy, 16 patients). A comparison between treated and untreated
      patients suggests that only patients with active and severe disease were treated
      whatever the precise diagnosis or the amount of axial disease in the
      spondyloarthropathy. After six months of treatment improvement was noted in 59
      patients unrelated to their subgroup or amount of axial disease. After a mean
      follow up of 20 months, 37 patients were still receiving treatment, 33 had
      discontinued the drug because of inefficacy, 14 because of side effects, six
      because of remission of the disease, and 11 for other reasons. Comparison between
      the beginning and end of treatment showed a statistically significant decrease in
      morning stiffness, erythrocyte sedimentation rate, and daily dose of non
      steroidal anti-inflammatory drugs (NSAIDs). It is concluded that: (a) a low
      percentage of patients with spondyloarthropathy have active disease requiring
      treatment with sulphasalazine despite the use of NSAIDs (27% in this study); (b)
      in this subgroup of patients sulphasalazine seems to be of clinically relevant
      benefit in 59%; and (c) this benefit does not seem to be correlated with either
      the precise diagnosis of spondyloarthropathy or the amount of axial disease.

PMID- 1358039
TI  - Retrovirus infections in the south of Cameroon.
AB  - The results of a national HIV seroprevalence survey carried out in 1986/87 showed
      a 1% HIV seroprevalence in the South of Cameroon, which is higher than in the
      other regions of the country. We here demonstrate the presence of HTLV-I
      infections in the South of Cameroon with possible clustering of infection in some
      villages. Some evidence suggestive of the presence of HTLV-II was obtained. Sera
      from patients with onchocerciasis did not react on HTLV testing. No HTLV
      associated haematological or neurological syndromes were observed during this
      survey. Regarding the human immunodeficiency viruses, the HIV-1 prevalence varied
      from 0 to 3% in the different populations studied. None of the subjects was HIV-2
      positive.

PMID- 1358040
TI  - Revival of the radial artery for coronary artery bypass grafting.
AB  - Eighteen years after its first introduction for coronary artery
      revascularization, the radial artery (RA) was reinvestigated because of
      unexpected good long-term results in the early series. Since July 1989, 104
      patients underwent myocardial revascularization using 122 RA grafts (18 patients
      received two grafts). The left internal mammary artery (IMA) was concomitantly
      used as a pedicled graft in 100 cases and the right IMA in 19 cases; a free IMA
      graft was used in 29 cases and a saphenous vein graft in 24 cases. A mean of 2.8
      grafts per patient were performed. Nine patients underwent associated procedures:
      carotid endarterectomy (3), aortic valve replacement (3), Bigelow procedure (1),
      and mitral valve repair (2). The target artery receiving the RA was the
      circumflex (n = 59), diagonal (n = 29), right coronary (n = 27), and left
      anterior descending (n = 7). One patient died (0.96%) and 2 had perioperative
      myocardial infarct. Sternal wound infection was noted in 3 cases of double IMA
      implantation. No ischemia of the hand was observed. All patients received
      diltiazem started intraoperatively and continued after discharge. In addition
      aspirin (100 mg/day) was given at discharge. Early angiographic controls (less
      than 2 weeks) were obtained in the first 50 consecutive patients and revealed 56
      of 56 patent RA grafts, 48 of 48 patent left IMA grafts, 11 of 11 patent right
      IMA grafts, 14 of 18 patent free IMA grafts, and 8 of 9 patent vein
      grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358041
TI  - Systolic hypertension in the elderly. Pathophysiology and management.
AB  - Isolated systolic hypertension occurs with increased prevalence in the elderly
      population. It is characterized by reduced vascular compliance, often combined
      with increased peripheral resistance. These changes are not specific to patients
      with systolic hypertension, occurring, perhaps to a lesser extent, in the
      normotensive aging population as well. Systolic hypertension is associated with a
      risk of cardiovascular morbidity and mortality that possibly exceeds that
      associated with systolic-diastolic hypertension. However, until the recent report
      of the Systolic Hypertension in the Elderly Program, the benefit of treatment of
      this population was undocumented. The Systolic Hypertension in the Elderly
      Program demonstrated that lowering of blood pressure with a diuretic, combined,
      when necessary, with a beta blocker, reduced the rate of myocardial infarction
      and stroke. Other agents may also be effective in lowering blood pressure,
      although their ability to reduce cardiovascular morbidity and mortality in this
      population remains to be documented. The results suggest that pharmacologic
      treatment be considered for patients older than 60 years whose systolic blood
      pressure remains above 160 mm Hg (with a diastolic pressure below 90 mm Hg).
      Whether treatment should be recommended for all patients with systolic
      hypertension, or, alternatively, for only those at higher risk for cardiovascular
      events, remains controversial.

PMID- 1358042
TI  - Survival in a cohort of human immunodeficiency virus-infected tuberculosis
      patients in New York City. Implications for the expansion of the AIDS case
      definition.
AB  - BACKGROUND: The occurrence of pulmonary tuberculosis in human immunodeficiency
      virus (HIV)-infected persons is believed to represent a less severe stage of HIV
      related disease with a more favorable prognosis than other acquired
      immunodeficiency syndrome (AIDS)-defining conditions; therefore, it has been
      excluded from the AIDS definition established by the Centers for Disease Control
      (Atlanta, Ga) criteria. METHODS: To determine the prognosis of patients with HIV
      related tuberculosis, we assessed the clinical, immunologic, and HIV infection
      status of a cohort of male subjects aged 20 to 44 years who were hospitalized
      with tuberculosis but without AIDS in New York City hospitals from 1985 through
      1986, and we determined their mortality through May 1991. RESULTS: The 58
      patients who agreed to participate were largely (90%) nonwhite and had a high
      prevalence of pulmonary tuberculosis (90%) and HIV infection (53%). Patients who
      were HIV seropositive had significantly lower CD4 cell counts (median, 0.136 x
      10(9)/L; range, 0.013 x 10(9) to 2.314 x 10(9)/L vs median, 0.765 x 10(9)/L;
      range, 0.284 x 10(9) to 2.333 x 10(9)/L), and, during the follow-up period, an
      83% mortality rate that was 7.5 times higher than the 11% rate in seronegative
      subjects. Survival analyses revealed that for all HIV-seropositive subjects the
      probability of death at 30 months was 72% and the median survival was 21 months
      (95% confidence interval, 15.5 to 26.5 months), while for HIV-seropositive
      subjects with CD4 cell counts of 0.2 x 10(9)/L or less, the probability of death
      at 30 months was 92% and the median survival was 15.75 months (95% confidence
      interval, 14.0 to 17.6 months). CONCLUSION: The prognosis for patients with HIV
      related pulmonary tuberculosis is poor, and those with CD4 cell counts of 0.2 x
      10(9)/L or less have survival patterns similar to that of patients with AIDS. We
      believe that these data support the expansion of the AIDS case definition to
      include persons with both pulmonary tuberculosis and severe HIV-related
      immunosuppression.

PMID- 1358043
TI  - Familial hyperinsulinism presenting in adults.
AB  - Two adult siblings presented with recurrent syncope due to severe
      hyperinsulinemic hypoglycemia. Exploratory laparotomy in the elder sibling showed
      a grossly normal pancreas, but histologic examination revealed islet cell
      hyperplasia. Neither sibling has any evidence of the multiple endocrine neoplasia
      type 1 syndrome, nor is there any other family history to suggest this diagnosis.
      To our knowledge, this is the first report of adult-onset familial
      hyperinsulinism without other manifestations of multiple endocrine neoplasia type
      1 syndrome. A simple provocative test for hyperinsulinism was also suggested by
      these cases. Because the initial patient related his symptoms to exercise, we
      used treadmill exercise in both patients to diagnose hyperinsulinism and observe
      its response to therapy.

PMID- 1358044
TI  - [Non invasive evaluation of cardiovascular effects of nebivolol in patients with
      cardiac insufficiency].
AB  - The results of several studies, mostly without controls, have suggested that
      betablockers, administered at progressively increasing doses, may be beneficial
      in cardiac failure. Based on this hypothesis, betablockers with a peripheral
      vasodilator effect, such as Nebivolol, could be particularly valuable in this
      indication. A preliminary study of its tolerance, haemodynamic and neurohormonal
      effects was carried out with a noninvasive methodology in 12 patients with
      cardiac failure in sinus rhythm, 8 men and 4 women (average age 53 +/- 12 years),
      all of whom had Class III or IV symptoms according to the NYHA Classification.
      The protocol had 2 phases: the first was an open phase during which Nebivolol was
      administered at a dose of 1 mg/day for 48 hours then 2.5 mg/day for 72 h. In the
      second phase, the patients were randomly separated into 2 groups, one to receive
      placebo and the other 2.5 mg for one week then 5 mg of Nebivolol for the 5
      remaining weeks. The heart rate decreased significantly from 70 +/- 3 to 63 +/- 4
      beats/min (p < 0.01) with Nebivolol 1 mg/day without further slowing at the 2.5
      mg dosage. During the randomised phase, the heart rate remained stable in the
      Nebivolol group but increased to its initial value in the group given placebo. No
      aggravation of symptoms was observed in the Nebivolol group. No significant
      changes in cardiac output, parameters of cardiac loading or contractility could
      be demonstrated after 6 weeks' treatment. During submaximal exercise testing,
      plasma concentrations of catecholamines and atrial natriuretic factor tended to
      be higher with Nebivolol than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358045
TI  - Overexpression of the c-erbB-2 oncogene in sarcomas and small round-cell tumors
      of childhood. An immunohistochemical investigation.
AB  - Amplification and overexpression of the c-erbB-2 oncogene have been associated
      with a poor prognosis in breast cancer. The present study evaluates c-erbB-2
      protein over-production in sarcomas and in small round-cell tumors of childhood
      by applying an immunohistochemical technique to formalin-fixed, paraffin-embedded
      tissues. This technique had previously demonstrated high sensitivity for the
      detection of c-erbB-2 activation. One peripheral neuroepithelioma demonstrated
      equivocal immunoreactivity for c-erbB-2 protein. There was no evidence of c-erbB
      2 protein overproduction in 11 angiosarcomas, 21 chondrosarcomas, 10 epithelioid
      sarcomas, 14 Ewing's sarcomas, 20 hepatoblastomas, nine leiomyosarcomas, 12
      liposarcomas, 13 malignant fibrous histiocytomas, nine malignant lymphomas, 15
      neuroblastomas/ganglioneuroblastomas, 16 neurofibrosarcomas, 10 osteosarcomas,
      seven peripheral neuroepitheliomas, 10 rhabdomyosarcomas, six synovial sarcomas,
      and 20 Wilm's tumors. We conclude that overproduction of the c-erbB-2 protein is
      rare or absent in these neoplasms and that its detection is therefore not likely
      to be of practical utility in their pathologic evaluation and prognostication.

PMID- 1358046
TI  - The effect of lipophilic substituents on the H2-histaminergic activity of some
      close analogues of impromidine.
AB  - The cimetidine-like moiety of the potent H2-agonist impromidine (9a) and three
      closely related guanidines (10a, 11a, and 12a) which are modified in the
      imidazolylpropyl portion, has been replaced by 2-[(2-pyridyl)methylthio]ethyl, 2
      (benzylthio)ethyl and 3,3-diphenylpropyl substituents. Guanidines 10-12 were
      obtained from acidic hydrolysis of corresponding N-benzoyl guanidines 7, 8, and
      15, accessible by successive aminolysis of diphenyl N-benzoyl carbonimidate (2)
      according to known methods. Compared with leads 10a and 11a lipophilic
      substitution affords almost equipotent H2-agonists 10b-d and 11b-d, while
      substituents with increasing lipophilicity enhance both intrinsic activity and
      potency of the weak partial agonist 12a at guinea-pig atrial H2-receptors.
      Guanidines 10-12 are weak H1-antagonists on the isolated guinea-pig ileum.

PMID- 1358047
TI  - Effects of major and minor surgery on plasma glutamine and cytokine levels.
AB  - The plasma levels of glutamine and cytokines have been measured frequently in
      patients before, during, and after elective abdominal aortic aneurysm surgery
      ("major surgery") or inguinal hernia repair ("minor surgery"). The plasma
      glutamine level declined rapidly following major surgery and remained markedly
      below preoperative levels until at least 7 days after surgery. This response of
      the plasma glutamine levels was significantly correlated with the production of
      interleukin 6 but not with that of interleukin 1, tumor necrosis factor, or
      interferon gamma. In contrast, following minor surgery, the plasma glutamine
      level was unchanged and the elaboration of interleukin 6 was attenuated. The
      decrease in the plasma glutamine level following major surgery may contribute to
      the state of immunosuppression, which follows major surgery, and the relationship
      between amino acid and cytokine metabolism is worthy of further study.

PMID- 1358049
TI  - Oro-facial trauma in children.
AB  - Dentoalveolar trauma is unfortunately a regular part of medical practice. The
      prompt management of such injuries is vital in re-establishing a healthy
      dentition. As well, the promotion of preventive equipment is paramount: from seat
      belts and bike helmets to mouthguards. The purchase of over the counter one-size
      fits-all mouthguards is not only a waste of money but dangerous. Well made
      mouthguards fitted by a dentist are a sensible investment to reduce the frequency
      and severity of costly dental injury and to preserve the attractive aesthetics of
      natural teeth (Figures 21 and 22). They must be worn in competition and at
      practice.

PMID- 1358048
TI  - Identification of muscarinic acetylcholine receptors in isolated canine lingual
      epithelia via voltage clamp measurements.
AB  - Acetylcholine (ACh), muscarine and methacholine all decreased the short-circuit
      current (Isc) measured across isolated canine lingual epithelia bathed in
      symmetrical solutions of Krebs-Henseleit buffer when added to the serosal, but
      not mucosal, solutions. Atropine inhibited the ACh-induced decrease in Isc
      whereas serosal solutions of 1 mM hexamethonium or 1 mM nicotine did not.
      Addition of a membrane-permeable analogue of cAMP also reduced Isc and, in the
      presence of this analogue, the decrease in Isc produced by ACh was markedly
      reduced. These data suggested the presence of muscarinic acetylcholine receptors
      in the serosal membranes of isolated canine lingual epithelia. The decrease in
      Isc induced by ACh may involve the inhibition of Ba(2+)-inhibitable K+ currents,
      as the addition of 100 microM BaCl2 to the serosal solution inhibited Isc and
      also completely inhibited the response produced by ACh. These findings suggest
      that responses of sensory fibres in lingual epithelia elicited by ACh may involve
      an interaction of ACh with epithelial cells rather than a direct interaction of
      ACh with receptors on sensory nerves.

PMID- 1358050
TI  - Distribution of tyrosine hydroxylase-like immunofluorescence in guinea pig
      vestibular ganglia and sensory areas.
AB  - The distribution of tyrosine hydroxylase (TH)-like immunofluorescence was
      analyzed in the guinea pig vestibular ganglia and end organs using a monoclonal
      antibody to TH. TH was chosen as a marker for the sympathetic fibers because TH
      regulates the first step of catecholamine synthesis by converting tyrosine to
      dopa. In the vestibular ganglia, there were TH-positive nerve fibers having
      distinct varicosities surrounding the vestibular ganglion cells. In the sensory
      areas, there was a sympathetic plexus in the subepithelial tissue of the saccule,
      the utricle, and the crista ampullaris. We speculated that the sympathetic
      innervation has a direct influence on the vestibular ganglion cells and diffuse
      influence on the capillary permeability.

PMID- 1358051
TI  - Filamentous forms of Bordetella avium: culture conditions and pathogenicity.
AB  - Difficulties in preparing suitable antigen for the microagglutination (MA) test
      led to the discovery of a filamentous form of Bordetella avium. Broth media high
      in nutrients, vigorous shaking, and incubation at 37 C appeared to promote the
      development of filamentous forms of the organism. Peptone broth did not induce
      the development of filamentous forms. Eleven different isolates having both
      smooth and rough colony types were tested and observed to form filaments of
      various lengths. Filamentous forms of B. avium hemagglutinated guinea pig
      erythrocytes were motile, had pili and flagella, and were stable up to the fourth
      or fifth passage in broth media, at which time a predominance of typical
      coccobacillus organisms were observed. Filamentous forms of B. avium originating
      from smooth-colony types were pathogenic in turkey poults, whereas the
      filamentous forms of B. avium originating from rough-colony types were not
      pathogenic.

PMID- 1358052
TI  - The biology of personality.
AB  - Historically, models of personality have generally postulated, or assumed, a link
      with biology. This century has witnessed a major revision of these ideas with
      both behavioural and psychoanalytic theorists emphasising life experiences as
      being largely responsible for behaviour as adults. Challenges to this assumption
      of the overwhelming importance of life experiences are reviewed. An extensive
      body of data now exists suggesting that biology contributes significantly to
      individual variability. This biological contribution occurs at a relatively low
      level in the central nervous system, best defined as temperament. Further
      research has suffered from the lack of a cohesive psychobiological model.
      Cloninger's tridimensional theory of personality is presented as a model which
      attempts to bridge the gap between theoretical temperamental traits,
      neurotransmitter function and clinical psychiatry. It is to be hoped that new
      theoretical models will be formulated which will focus on the importance of
      temperamental variables in psychiatric disorders.

PMID- 1358053
TI  - Symptomatic response to antipsychotics differs between recent onset and recurrent
      chronic schizophrenic patients.
AB  - The symptomatic response to standard antipsychotic treatment was assessed over
      the first 4 weeks of hospitalisation in 39 patients with DSM-III schizophrenia,
      active phase, using the Brief Psychiatric Rating Scale (BPRS). While highly
      significant improvement was noted overall, 36% of patients either did not improve
      or worsened. Furthermore there was no diminution in the withdrawal-retardation
      factor of the BPRS. Patients experiencing their first admission to hospital, all
      with recent-onset illness, were then compared with patients who presented with a
      recurrence and had illness of at least 3 years duration. Despite similarities in
      overall response, withdrawal-retardation scores did not diminish in recent-onset
      patients, in contrast to multiple admissions who demonstrated significant
      improvement. These findings suggest greater responsiveness of negative symptoms
      to treatment in patients with longstanding illness, and possibly a poorer
      prognosis in first admission patients with deficit manifestations.

PMID- 1358054
TI  - Neurotransmitter receptors involved in post-training memory processing by the
      amygdala, medial septum, and hippocampus of the rat.
AB  - Rats were trained and tested in habituation to a novel environment and step-down
      inhibitory avoidance. Immediately after training in each task the animals
      received intra-amygdala, intraseptal, or intrahippocampal micro-injections of
      agonists and antagonists of various neurotransmitter receptors. In the habitation
      task, intrahippocampal, but not intra-amygdala or intraseptal administration of
      the NMDA receptor antagonist aminophosphornopentanoic acid (AP5, 5.0 micrograms)
      or of the muscarinic receptor antagonist, scopolamine (2.0 micrograms) caused
      amnesia and the indirect antagonist of GABA-A receptors, picrotoxin (0.08
      microgram), caused retrograde facilitation. Intrahippocampal administration of
      the respective agonists, glutamate, oxotremorine, and muscimol, had effects of
      their own opposite to those of the blockers, and norepinephrine (0.3 microgram)
      caused memory facilitation. In the avoidance task, results obtained with drug
      infusions given into the three structures were very similar: in all cases, AP5,
      scopolamine, and muscimol were amnestic, and glutamate, oxotremorine,
      norepinephrine, and picrotoxin caused memory facilitation. In addition, also in
      the three structures, picrotoxin counteracted the amnestic effect of AP5 and/or
      scopolamine and the beta-adrenoceptor blocker, timolol (0.3 microgram), while
      ineffective on its own, attenuated all the effects of picrotoxin. The results
      suggest that similar synaptic mechanisms in the amygdala, medial septum, and
      hippocampus are involved in memory consolidation: NMDA, muscarinic, and beta
      noradrenergic receptors stimulate and GABA-A receptors inhibit this process, and
      beta-noradrenergic receptors modulate the GABAergic synapses. In the avoidance
      task these mechanisms operate in the three structures: in habituation only those
      in the hippocampus are operative. Possibly in each structure these mechanisms
      regulate, if not actually consolidate, a different aspect, component, or form of
      memory.

PMID- 1358055
TI  - Strain-dependent effects of post-training dopamine receptor agonists and
      antagonists on memory storage in mice.
AB  - Post-training administration of the selective D1 or D2 agonists SKF 38393 and LY
      171555 dose dependently impairs retention of an inhibitory avoidance response in
      DBA/2 mice. In agreement, the selective D1 or D2 antagonists SCH 23390 and (-)
      sulpiride improve retention. These effects are opposite to those observed in the
      C57BL/6 strain, as previously reported. Moreover, B6D2F1 hybrids present a
      response to SKF 38393, LY 171555, SCH 23390, and (-)-sulpiride that parallels
      that of the C57BL/6 strain, thus suggesting that the neural mechanisms underlying
      the effects of DA agonists or antagonists on memory processes may be inherited
      through a dominant mode of inheritance.

PMID- 1358056
TI  - The homeotic gene spineless-aristapedia affects geotaxis in Drosophila
      melanogaster.
AB  - The homeotic mutation spineless-aristapedia (ss(a)) transforms the aristae into
      second tarsi. Flies with a ss(a) phenotype also show extremely positive geotaxis
      as measured in a Hirsch-type geotaxis maze. Other antennal mutants and flies with
      their aristae amputated do not show such extreme positive geotaxis. Deletion
      analysis has comapped the geotaxis effect with ss(a) in band 89C on the third
      chromosome. Finally, a biometrical analysis has detected additional genes on the
      X chromosome that also affects geotaxis.

PMID- 1358057
TI  - Medication use and the assessment of agoraphobic avoidance.
AB  - Many anxiety disorder patients who present for behaviour therapy are already
      taking anxiolytic medications. The present study added a new subscale to the
      Mobility Inventory labelled 'Without Medication' to assess possible reliance on
      medication for coping with phobic situations. 121 Patients with panic-related
      disorders were administered the scale. The results supported the reliability and
      validity of the existing Mobility Inventory subscales in general and of the new
      subscale in particular. It appears to reliably assess a clinically important
      domain that is not measured in traditional self-report measures of phobic
      avoidance.

PMID- 1358058
TI  - Fearful distortions.
AB  - Clinical observations suggesting that perceptual distortions can take place
      during episodes of fear are described, and two hypotheses are set out: (1)
      perceptual distortions occur during episodes of fear, and (2) such distortions
      decline after reduction of the pertinent fear. An experiment in which fearful
      subjects were asked to report their perceptions of a feared object during
      episodes of fear, and then again after fear-reduction, was carried out. Snake
      phobic and spider-phobic subjects showed evidence of some distortions in the
      activity of the pertinent fear object, but no distortions of size. After the
      reduction of the relevant fear, the subjects reported significant declines in the
      activity of the pertinent animal. The two hypotheses received partial support.

PMID- 1358059
TI  - Plant polyphenols: synthesis, properties, significance. Proceedings of the 2d
      North American Tannin Conference. Houghton, Michigan, June 17-21, 1991.

PMID- 1358060
TI  - A model of cytosolic calcium regulation and autacoids production in vascular
      endothelial cell.
AB  - A model of vascular endothelial cell is proposed to describe the mechanisms by
      which cytosolic calcium (Cai) is modulated and endothelium-derived relaxing
      factor (EDRF) and prostacyclin (PGI2) are released when the cell is stimulated by
      agonist. The intracellular Ca2+ store of the model cell is comprised of a
      superficial (sc) and a deep (dc) compartment. The dc Ca2+ content is refilled by
      the sc whose [Ca2+] is the same as extracellular Ca2+. Inositol (1,4,5)
      trisphosphate (IP3) produced by agonist modifies the dc permeability which
      discharges its Ca2+ to the cytosol. The increase of Cai induces Ca2+ released
      from the sc. Ca(2+)-activated K+ current hyperpolarises the cell. The raised Cai
      releases PGI2 in the presence of IP3 while EDRF is released by Cai. The model
      explains satisfactorily the Ca2+ transient and autacoids production of the aortic
      endothelial cell without the need of calcium influx from extracellular space. The
      cytoplasmic Ca2+ oscillations observed in human endothelial cell from umbilical
      veins were reproduced by the model. Production of EDRF by the artery due to
      increase in pressure was also simulated.

PMID- 1358061
TI  - Ethanol increases receptor-dependent cyclic AMP production in cultured
      hepatocytes by decreasing G(i)-mediated inhibition.
AB  - Increasing evidence suggests that ethanol-induced changes in cyclic AMP (cAMP)
      signal transduction play a critical role in the acute and chronic effects of
      ethanol. Here we have investigated the effects of ethanol on cAMP signal
      transduction in primary cultures of rat hepatocytes. Acute exposure to ethanol
      had a biphasic effect on glucagon-receptor-dependent cAMP production in intact
      cells: 25-50 mM-ethanol decreased cAMP, whereas treatment with 100-200 mM-ethanol
      increased cAMP. After chronic exposure to 50-200 mM-ethanol for 48 h in culture,
      glucagon-receptor-dependent cAMP levels were increased, but no change in glucagon
      receptor number was observed. These effects of ethanol were independent of
      ethanol oxidation. Chronic ethanol treatment also increased adenosine-receptor-
      and forskolin-stimulated cAMP production. Increased cAMP production was also
      observed upon stimulation of adenylate cyclase with glucagon, forskolin and F- in
      membranes isolated from cells cultured with 100 mM-ethanol for 48 h. However, no
      differences were observed in basal and MnCl2-stimulated adenylate cyclase
      activity. The quantity of alpha i protein was decreased by 35% after chronic
      ethanol treatment, but no change in the quantity of alpha s protein was detected.
      Decreased alpha i protein was associated with a decrease in G(i) function, as
      assessed by the ability of 0.1 nM-guanosine 5'-[beta gamma-imido]triphosphate and
      1 microM-somatostatin to inhibit forskolin-stimulated adenylate cyclase activity.
      Taken together, these results suggest that chronic exposure to ethanol increases
      receptor-dependent cAMP production in hepatocytes by decreasing the quantity of
      alpha i protein at the plasma membrane and thereby decreasing the inhibitory
      effects of G(i) on adenylate cyclase activity.

PMID- 1358063
TI  - Molecular modelling of D2-like dopamine receptors.
AB  - Three-dimensional computer models of the rat D2, D3 and D4 dopamine receptor
      subtypes have been constructed based on the diffraction co-ordinates for
      bacteriorhodopsin, another membrane-bound protein containing seven transmembrane
      domains presumed to be arranged in a similar spatial orientation. Models were
      assembled by aligning the putative transmembrane domains of the dopamine
      receptors with those of bacteriorhodopsin using sequence similarities, and then
      superimposing these modelled alpha-helices on to the bacteriorhodopsin-derived co
      ordinates. These models explore the potential hydrogen bonding, electrostatic and
      stacking interactions within the receptor which may be important for maintaining
      the conformation of these receptors, and thereby provide target sites for agonist
      binding. Proposed interactions between the catecholamine ligands and these
      receptors appear to account for the affinity, although not the specificity, of
      these agonist ligands for the different dopamine receptor subtypes. Such models
      will be useful for establishing structure-function relationships between ligands
      and the dopamine receptors, and may ultimately provide a template for the design
      of receptor-specific drugs.

PMID- 1358064
TI  - A novel transglutaminase-catalyzed posttranslational modification of HIV-1
      aspartyl protease.
AB  - We demonstrate that HIV-1 aspartyl protease (AP), the enzyme essential for the
      maturation of the AIDS virus, covalently incorporates spermidine catalyzed by
      guinea pig liver transglutaminase (TGase) and human coagulation factor XIIIa.
      Preliminary evidence indicates that there are at least three reactive glutamyl
      and lysyl residues in AP which act as acyl donor and acceptor respectively in a
      TGase reaction. SDS-PAGE and chromatographic analyses indicate that the two
      TGases tested catalyze the incorporation of radioactive spermidine into pure HIV
      1 AP. The chemical identification and quantitation of (gamma-glutamyl) spermidine
      isopeptide provide conclusive evidence that the formation of this derivative is
      catalyzed by TGase. These results imply that TGase-catalyzed post-translational
      modification of HIV-1 AP may take place in a manner similar to the ones
      demonstrated in porcine pancreatic phospholipase A2.

PMID- 1358062
TI  - Modulation in vivo of beta-adrenergic-receptor subtypes in rat brown adipose
      tissue by the thermogenic agonist Ro 16-8714.
AB  - The number of beta 3-adrenergic receptors (AR) in plasma membranes from
      interscapular brown adipose tissue (IBAT) was decreased by 62% in lean Zucker
      rats treated with the thermogenic beta-adrenergic agonist Ro 16-8714 as compared
      with controls after 72 h of treatment. The loss of beta 3-AR number was preceded
      by a 93% decrease in the steady-state level of beta 3-AR mRNA at 30 h. Similar
      results were obtained in obese (fa/fa) Zucker rats. Ro 16-8714 had no effect on
      the number of beta 1- and beta 2-ARs in IBAT. This is the first report to
      demonstrate that the beta 3-AR in IBAT can be specifically down-regulated in vivo
      by exposure to a thermogenic agonist.

PMID- 1358065
TI  - Hypotensive effect associated with a phospholipase C-delta 1 gene mutation in the
      spontaneously hypertensive rat.
AB  - To identify the genes responsible for blood pressure in the spontaneously
      hypertensive rat strain, we performed a cosegregation analysis between the
      genotype and blood pressure in a set of male F2 rats obtained by crossmating SHR
      with Wistar-Kyoto rats, a parental normotensive strain. Our investigation
      revealed that the phospholipase C-delta 1 polymorphism, which resulted in
      missense mutation, cosegregates with the lower blood pressure in SHR, and that
      PLC-delta 1 gene is located on chromosome 8. On the other hand, we found the lack
      of cosegregation between blood pressure and the nerve growth factor receptor
      gene, which is linked to a hypertensinogenic gene locus (denoted as BP/SP-1) on
      chromosome 10. We propose that PLC-delta 1 gene itself of closely linked gene on
      chromosome 8 is a new candidate with the hypotensive effect, and that BP-SP1
      locus does not directly contribute to blood pressure elevation in original SHR.

PMID- 1358067
TI  - Expression of only one of two types of mRNA transcribed from the serine
      dehydratase gene is repressed in hepatoma cells.
AB  - The expressions of mRNA for serine dehydratase in H4IIE, HTC, and HepG2 hepatoma
      cells were investigated. Of the two types of mRNA transcribed from the single
      copy of the rat serine dehydratase gene, expression of only that encoding 35 kDa
      serine dehydratase is repressed in these cells. The other type coding the 8.9 kDa
      truncated translation product is expressed at a similar level to that in
      hepatocytes in primary culture and is not under hormonal control.

PMID- 1358066
TI  - Effect of the weak Ca(2+)-binding site of subtilisin J by site-directed
      mutagenesis on heat stability.
AB  - The functional role of the negatively charged amino acid residue in subtilisin J
      from Bacillus stearothermophilus has been investigated by site-directed
      mutagenesis. Glu-195 located at the weak Ca2+-binding site was replaced with Gln
      to examine the role of Glu-195 in the heat stability of subtilisin J. Mutant
      enzyme was expressed in Bacillus subtilis and was purified from the culture
      supernatant. When the mutant enzyme was expressed at 37 degrees C in the presence
      of 2mM calcium chloride, the pattern of enzyme production was quite different
      from that of wild-type. The purified Gln-195 mutant enzyme was analyzed with
      respect to optimal temperature, optimal pH, and heat stability. The mutation was
      found to decrease the heat stability but not catalytic efficiency (kcat/Km) and
      optimal pH. These results demonstrate the important role of the negatively
      charged side chains at the weak Ca(2+)-binding site in the heat stability of
      subtilisin.

PMID- 1358069
TI  - Isolation of [Pro2,Met13]somatostatin-14 and somatostatin-14 from the frog brain
      reveals the existence of a somatostatin gene family in a tetrapod.
AB  - Two somatostatin-related peptides were isolated in pure form from an extract of
      the brain of the European green frog, Rana ridibunda. The primary structure of
      the most abundant component was identical to that of mammalian somatostatin-14.
      The primary structure of the second component, present in approximately 5% of the
      abundance of somatostatin-14, was established as Ala-Pro-Cys-Lys-Asn-Phe-Phe-Trp
      Lys-Thr-Phe-Thr-Met-Cys. This sequence shows two substitutions (Pro for Gly2 and
      Met for Ser13) compared with mammalian somatostatin-14. The data provide evidence
      for a somatostatin gene family in tetrapods as well as in teleost fish.

PMID- 1358068
TI  - P-glycoprotein possesses a 1,4-dihydropyridine-selective drug acceptor site which
      is alloserically coupled to a vinca-alkaloid-selective binding site.
AB  - [3H]Vinblastine bound with high affinity to surface membranes prepared from
      H69/LX4 cells which express P-glycoprotein (P-gp) and as a consequence are
      multidrug resistant (MDR). The KD was 9.8 +/- 1.5 nM and density of sites 31.2 +/
      8.6 pmol/mg of protein. [3H]Vinblastine binding was inhibited by cytotoxics and
      agents known to reverse MDR. 1,4-Dihydropyridine MDR reversing agents including
      nicardipine and nifedipine accelerated the dissociation of [3H]vinblastine from P
      gp indicating a negative heterotropic allosteric effect. Cyclosporin A,
      vincristine and actinomycin D did not alter [3H]vinblastine dissociation
      kinetics. It is concluded that P-gp possesses at least two allosterically coupled
      drug acceptor sites, receptor site-1 that is selective for vinca alkaloids and
      cyclosporin A, and receptor site-2 that is selective for 1,4-dihydropyridines.

PMID- 1358070
TI  - Purification of testicular transglutaminase by hydrophobic chromatography on
      phenyl-sepharose.
AB  - We developed a procedure for purification to homogeneity of cytosolic
      transglutaminase from bovine testes, by means of anion exchange, size exclusion
      and hydrophobic chromatography. The crucial step is chromatography on Phenyl
      sepharose, with specific elution by the inhibitor GTP. The enzyme displays the
      properties of type 2 transglutaminases.

PMID- 1358071
TI  - Effects of aging on renal response to parathyroid hormone in vitro.
AB  - Renal cortex homogenates from aged (greater than 5 y) rabbits showed decreased
      specific activities of brush border membrane enzymes compared to those from
      control young (6 m) rabbits but the specific enzyme activities of basolateral
      membrane, endoplasmic reticulum and mitochondria did not differ between the two
      groups. The stimulatory effects of parathyroid hormone (PTH) on the Ca(2+)-pump
      enzyme [(Ca(2+)+Mg2+)-ATPase] activity in kidney cortex homogenates were markedly
      less in aged rabbits, but the effect of cAMP on this enzyme activity was similar.
      Moreover, the production of cAMP induced by PTH was markedly less in the renal
      cortex homogenates from aged rabbits. From these results, we have proposed the
      following mechanism; aging--decrease in the response of cAMP to PTH in renal
      cortex--decrease in the stimulatory effect of PTH via cAMP on the Ca(2+)-pump
      enzyme--decreased reabsorption of Ca2+ from ureter--increased urinary Ca2+
      secretion. This pathway may contribute to the worsening of senile osteoporosis.

PMID- 1358072
TI  - Thiol-mediated generation of nitric oxide accounts for the vasodilator action of
      furoxans.
AB  - Furoxans (1,2,5-oxadiazole-2-oxides) are widely used in organic chemistry as
      intermediate compounds for the synthesis of various heterocycles. Despite the
      fact that some furoxans have been found to possess remarkable biological
      activities, up to now no systematic study on their mode of action has been
      reported. The aim of the present study was to investigate the molecular mode of
      the vasodilator action of furoxans. Furoxans, but not the corresponding furazans,
      concentration-dependently increased coronary flow in an isolated working rat
      heart preparation. This effect was blunted upon coinfusion with methylene blue.
      All tested furoxans were demonstrated to increase potently the activity of
      soluble guanylate cyclase. Enzyme stimulation was found to be mediated by the
      generation of nitric oxide (NO) following chemical reaction of the furoxans with
      sulfhydryl groups of low molecular weight thiols and proteins. Furoxans are thus
      prodrugs which increase the level of cyclic GMP via formation of NO and may
      therefore be classified as nitrovasodilators. Along with the generation of NO,
      nitrite and nitrate ions and S-nitrosothiols were formed. The rates of formation
      of these metabolites, however, did not appear to be related to enzyme
      stimulation. A tentative reaction scheme that fits the obtained experimental data
      is proposed. Recently reported cytotoxic, mutagenic, immunosuppressive and
      anticancer effects of furoxans are discussed in the light of their ability to
      release NO upon reaction with thiols.

PMID- 1358073
TI  - MY-1250, a major metabolite of the anti-allergic drug repirinast, induces
      phosphorylation of a 78-kDa protein in rat mast cells.
AB  - Repirinast (MY-5116; isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2
      c]quinoline-2-carboxylate) is an anti-allergic drug of demonstrated effectiveness
      for treating bronchial asthma in humans. MY-1250 (5,6-dihydro-7,8-dimethyl-4,5
      dioxo-4H-pyrano [3,2-c]quinoline-2-carboxylic acid), the major active metabolite
      of repirinast, inhibits antigen-induced histamine release from sensitized rat
      peritoneal exudate cells (PEC). When purified rat mast cells were treated with MY
      1250 (2.5 x 10(-5) M) for 1 min, phosphorylation of a specific mast cell protein
      of apparent molecular mass of 78 kDa was observed as previously reported for
      sodium cromoglycate (SCG). Phosphorylation of this protein induced by MY-1250 and
      SCG occurred in a concentration-dependent manner with IC50 values of 2.0 x 10(-7)
      and 1.4 x 10(-5) M, respectively. MY-1250 did not inhibit calcium ionophore
      A23187 (1 microgram/mL)-induced histamine release from rat PEC. In the presence
      of calcium ionophore A23187 (1 microgram/mL), phosphorylation of this protein
      induced by MY-1250 was not evident. In conclusion, MY-1250 induced
      phosphorylation of a 78-kDa protein in rat mast cells and MY-1250 may inhibit
      histamine release by regulating phosphorylation of this protein in rat mast
      cells.

PMID- 1358074
TI  - Pharmacokinetics of steroidal muscle relaxants in isolated perfused rat liver.
AB  - Both in humans and animals hepatic elimination is an important factor determining
      the duration of action of non-depolarizing neuromuscular blocking drugs. To
      elucidate the hepato-biliary disposition of muscle relaxants the pharmacokinetics
      of several structurally related but physicochemically distinct steroidal
      neuromuscular blocking drugs were studied in isolated perfused rat livers.
      Pharmacokinetics analysis with the DIFFIT computer program enabled the
      simultaneous fitting of independently measured perfusate disappearance and
      biliary excretion rate curves using a numerical approach. The hepatic disposition
      of the steroidal muscle relaxants could be adequately described by a three
      compartment model with elimination from the peripheral compartment V2 (biliary
      excretion) and storage in a deep compartment (V3) connected to V2. In addition,
      for vecuronium only slow ester hydrolysis occurring in V2 and V3 was included in
      the model. The lipophilicity rather than the relative mobility of the muscle
      relaxants showed a positive relationship with biliary clearance (Cl20) and the
      initial hepatic uptake (Cl12), indicating that hepato-biliary transport of these
      organic cations is highly dependent on the hydrophobic character of the
      compounds. In addition, net hepatic uptake of the steroidal cations was
      influenced markedly by transport from the liver to perfusate (hepatic efflux).
      This hepatic efflux (k21) decreased with increasing lipophilicity. In contrast,
      the extent of intracellular sequestration into deep compartments, indicated by
      high k23/k32 ratios, seemed to be inversely related to the lipophilicity of the
      muscle relaxants and might explain the observed prolonged hepatic storage of some
      of these compounds. In combination with data from subfractionation studies the
      results indicate that the pharmacokinetic analysis of the hepatic disposition of
      steroidal muscle relaxants may be used to evaluate actual transport phenomena
      participating in the hepatic disposition of these drugs.

PMID- 1358075
TI  - Substituted imidazo[1,2-b]pyridazines. New compounds with activity at central and
      peripheral benzodiazepine receptors.
AB  - A large range of substituted imidazo[1,2-b]pyridazines have been synthesized, and
      a number of potent ligands at central benzodiazepine (Bz) receptors on rat brain
      membranes have been identified in initial binding screens using [3H]diazepam. For
      those tested more extensively, binding studies conducted in the presence and
      absence of gamma-aminobutyric acid suggest that they were full receptor agonists.
      Some preliminary evidence was found suggesting some species selectivity, i.e.
      several of the compounds were more active in in vivo tests in rats than in mice.
      The agonist activity of these 2-phenyl (and substituted phenyl) imidazo[1,2
      b]pyridazines is consistent with the model of Bz receptor ligands as proposed by
      Fryer [Raven Press, 1983, pp. 7-20]. Several compounds were identified which had
      more selective activity at peripheral-type (mitochondrial) Bz binding sites.
      Thus, substituted imidazo[1,2-b]pyridazines represent yet another class of low
      molecular mass compounds which have activity at Bz receptor sites.

PMID- 1358076
TI  - Effects of acute alcohol intoxication on gluconeogenesis and its hormonal
      responsiveness in isolated, perfused rat liver.
AB  - Rats were acutely administered ethanol as a primed constant infusion in order to
      produce sustained blood ethanol levels of 8-12 or 55-65 mM. At the end of ethanol
      infusion the livers were either freeze-clamped in vivo or isolated and perfused
      for metabolic studies. The rate of gluconeogenesis and its responsiveness to
      phenylephrine (10 microM), prostaglandin F2 alpha (5 microM) and glucagon (10
      nM), as well as the redox state of the cytosolic NAD(+)-NADH system were assessed
      in livers isolated from acutely ethanol-treated rats, and subsequently perfused
      without ethanol. For liver clamped in vivo, high- but not low-ethanol treatment
      decreased the ATP content by 31% and slightly increased ADP and AMP content,
      resulting in a decreased energy charge (11%). Glutamate and aspartate content was
      also increased in high-dose ethanol-infused rats with no changes in malate and 2
      oxoglutarate content. Gluconeogenesis with saturating concentrations of lactate
      (4 mM)+pyruvate (0.4 mM) was delayed in reaching a plateau in the livers of high
      dose ethanol-treated rats and its response to all three stimulators was impaired.
      Low-dose ethanol treatment only decreased the liver response to phenylephrine.
      While the perfused livers of low-dose ethanol-treated rats displayed no changes
      in adenine nucleotide content, the livers of high-dose ethanol-treated rats had a
      decreased ATP (35%) and an increased AMP (77%) content, paralleled by a fall in
      the total adenine nucleotides (14%) and energy charge (14%). No differences were
      observed between the saline- and ethanol-treated rats with respect to malate
      aspartate shuttle intermediate concentration in perfused livers. Also, the livers
      of high-, but not low-dose ethanol-treated rats had a more negative value of
      NAD(+)-NADH redox state as compared to the livers of control rats. The data
      suggest that acute ethanol intoxication produces changes in liver metabolism and
      its responsiveness to hormones/agonists that are demonstrable for at least 2 hr
      after isolation and perfusion of the liver.

PMID- 1358077
TI  - [Computer analysis and comparison of neurotoxin structures from snake and the
      anemone Radianthus macrodactylus].
AB  - Evolutionary trees of proteins analysed by means of computer comparative methods
      were reconstructed and the level of the structure and functional relationship was
      revealed. The distance between the percent amino acid contents was used to
      classify a group of toxins from the sea anemone Radianthus macrodactylus, which
      proved to belong to long neurotoxins. The scores were calculated by the pattern
      recognition method. By the use of the distance values, ten phospholipases A2 were
      divided into two groups, containing representatives of the most closely related
      organisms.

PMID- 1358078
TI  - Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in
      rheumatoid arthritis. A metaanalysis of published clinical trials.
AB  - OBJECTIVE: Preferred drugs for rheumatoid arthritis (RA) should be those that
      have maximal efficacy with the least toxicity. We evaluated the efficacy and
      toxicity tradeoffs for drugs frequently used in the treatment of RA. METHODS: We
      updated 2 metaanalyses of published clinical trials, by adding trials published
      through 1990 and trials of azathioprine (AZA). We tested 3 different definitions
      of efficacy, each plotted against 3 different toxicity measures, for antimalarial
      drugs, methotrexate (MTX), auranofin, injectable gold, D-penicillamine,
      sulfasalazine (SSZ), AZA, and placebo. Efficacy measures included composite
      efficacy (a combination of joint count, grip strength, and erythrocyte
      sedimentation rate), tender joint count alone, and a measure based on how many
      patients dropped out due to inefficacy. Toxicity measures were the proportion
      dropping out due to toxicity, the same dropouts with side effects weighted for
      severity using a modification of a published toxicity index, and the proportion
      with severe toxicities (defined as a score of at least 7 of 10 on the toxicity
      index). The latter were usually organ toxicities (e.g., cytopenias and renal
      involvement). RESULTS: All 9 efficacy/toxicity tradeoff plots suggested that MTX
      and antimalarial drugs had the highest efficacy relative to toxicity. MTX scored
      among the most efficacious of the drugs and, of these, had the least toxicity.
      Antimalarial drugs, though showing only moderate efficacy, had the lowest
      toxicity rate of all the drugs. SSZ scored close to MTX but was, in general,
      slightly more toxic. CONCLUSION: In the short-term context of clinical trials,
      antimalarial drugs and MTX have the best efficacy/toxicity tradeoffs and may,
      therefore, be the preferred drugs.

PMID- 1358079
TI  - Third International Conference on Systemic Lupus Erythematosus.
AB  - A Fourth International Conference on Systemic Lupus Erythematosus will be held in
      Jerusalem in March 1995. We look forward to a better understanding of the
      molecular, genetic, immunologic, and clinical aspects of the disease and trust
      that this knowledge will result in improved treatment.

PMID- 1358080
TI  - Neuroleptic activity of 10-(4-methyl-1-piperazinyl)-thieno[3,2-b]
      [1,5]benzoxazepine and benzothiazepine derivatives.
AB  - Two series of compounds, structurally related to clozapine (CAS 5786-21-0), were
      tested for their neuroleptic activity. The derivatives 7-chloro-10-(4-methyl-1
      piperazinyl)-thieno[3,2-b][1,5]benzoxazepine and 7-chloro-10-(4-methyl-1
      piperazinyl)-thieno[3,2-b][1,5]benzothiazepine at high doses were not
      cataleptogenic and only very weakly antagonized the amphetamine-or apomorphine
      induced stereotyped behaviour in the rat, whereas at low doses they antagonized
      the amphetamine-induced hypermotility in mice. Thus these compounds might be
      efficient neuroleptics with little propensity to cause extrapyramidal side
      effects. On the other hand, the unsubstituted compound 10-(4-methyl-1
      piperazinyl)-thieno[3,2-b][1,5]benzothiazepine appeared to be an efficient
      neuroleptic agent with a greater propensity to cause these side effects.

PMID- 1358081
TI  - Modification of lymphoid subsets by chronic ethanol consumption in C57Bl/6 mice
      infected with LP-BM5 murine leukemia virus.
AB  - The relatively high incidence of infectious disease in alcoholics is attributed
      to the immunosuppressive effects of alcohol. The potential role of alcohol as
      cofactor in HIV infection and in the development and expression of AIDS is
      suggested but unknown. In order to understand better the contribution of alcohol
      to immune dysfunction following HIV infection, we assessed the presence of
      specific markers on thymus and spleen cells in C57B1/6 mice infected with LP-BM5
      murine leukemia virus and fed ethanol-containing diets. In the first experiments,
      mice were fed diets containing 0, 4.5, 5.5, and 6% (v/v) ethanol for 14 weeks.
      High ethanol exposure (6%) resulted in severe dehydration and death after 7
      weeks. Although moderately low intakes of ethanol did not significantly modify
      percentages of T and B cells, they increased the absolute number of mature T, B,
      and CD4+ cells and decreased percentages of Thy 1.2+ cells. In the second
      experiment, mice were infected with LP-BM5 murine leukemia retrovirus and fed
      diets containing 5% ethanol in a regimen of 5 days of ethanol diet and 2 days of
      diet without alcohol for 12 weeks. Ethanol exposure in the retrovirally infected
      mice showed a marked decrease in Thy 1.2+ (P < 0.05). Moderate decreases in
      percentages of CD4+, CD8+, CD5+ cells and an increase in Ia+ cells were also
      observed in the retrovirus/infected ethanol-treated mice. Moderate ethanol
      consumption during retroviral infection induced mild/moderate changes on lymphoid
      cells. Ethanol consumption may accelerate the progression of murine AIDS through
      such changes in the lymphoid cells of the spleen.

PMID- 1358083
TI  - 6th Congress of the International Child Neurology Association. 1st Iberoamerican
      Congress of Pediatric Neurology. Buenos Aires, Argentina, November 8-13, 1992.
      Abstracts.

PMID- 1358084
TI  - Report from an international symposium on typhoid fever.

PMID- 1358082
TI  - Proton spectroscopic imaging in cerebral ischaemia. Where we stand and what can
      be expected.

PMID- 1358086
TI  - European Respiratory Society annual congress. August 29-September 3, 1992.
      Abstracts.

PMID- 1358085
TI  - Polyamine metabolism in different pathological states of the brain.
AB  - Biosynthesis of the polyamines spermidine and spermine and their precursor
      putrescine is controlled by the activity of the two key enzymes ornithine
      decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC). In the adult
      brain, polyamine synthesis is activated by a variety of physiological and
      pathological stimuli, resulting most prominently in an increase in ODC activity
      and putrescine levels. The sharp rise in putrescine levels observed following
      severe cellular stress is most probably the result of an increase in ODC activity
      and decrease in SAMDC activity or an activation of the interconversion of
      spermidine into putrescine via the enzymes spermidine N-acetyltransferase and
      polyamine oxidase. Spermidine and spermine levels are usually less affected by
      stress and are reduced in severely injured areas. Changes of polyamine synthesis
      and metabolism are most pronounced in those pathological conditions that induce
      cell injury, such as severe metabolic stress, exposure to neurotoxins or seizure.
      Putrescine levels correlate closely with the density of cell necrosis. Because of
      the close relationship between the extent of post-stress changes in polyamine
      metabolism and density of cellular injury, it has been suggested that polyamines
      play a role in the manifestation of structural defects. Four different mechanisms
      of polyamine-dependent cell injury are plausible: (1) an overactivation of
      calcium fluxes and neurotransmitter release in areas with an overshoot in
      putrescine formation; (2) disturbances of the calcium homeostasis resulting from
      an impairment of the calcium buffering capacity of mitochondria in regions in
      which spermine levels are reduced; (3) an overactivation of the NMDA receptor
      complex caused by a release of polyamines into the extracellular space during
      ischemia or after ischemia and prolonged recirculation in the tissue surrounding
      severely damaged areas; (4) an overproduction of hydrogen peroxide resulting from
      an activation of the interconversion of spermidine into putrescine via the
      enzymes spermidine N-acetyltransferase and polyamine oxidase. Insofar as a sharp
      activation of polyamine synthesis is a common response to a variety of
      physiological and pathological stimuli, studying stress-induced changes in
      polyamine synthesis and metabolism may help to elucidate the molecular mechanisms
      involved in the development of cell injury induced by severe stress.

PMID- 1358087
TI  - 2nd International Conference on the Computerized Cytology and Histology
      Laboratory. Chicago, Illinois, March 8-11, 1992. Abstracts.

PMID- 1358088
TI  - Serotonin 5-HT1-like receptors mediate hyperactivity in rats induced by 3,4
      methylenedioxymethamphetamine.
AB  - This study was designed to evaluate the role of different serotonin (5-HT)
      receptor subtypes in mediating the effects of 3,4-methylenedioxymethamphetamine
      (MDMA) on rat exploration of a novel environment. The active enantiomer of MDMA,
      S-MDMA increases forward locomotion and suppresses investigatory behaviors and
      local movements. Previous studies indicate that S-MDMA-induced hyperactivity
      depends upon drug-induced 5-HT release. Propranolol and pindolol, beta
      noradrenergic antagonists with affinity for 5-HT1 receptors, antagonized the S
      MDMA-induced locomotor hyperactivity. The antagonism by propranolol was
      stereoselective. In contrast, a beta-noradrenergic antagonist that is a weaker
      antagonist of 5-HT receptors, betaxolol, was much less effective at blocking the
      behavioral response to S-MDMA. Among nonselective 5-HT antagonists, methiothepin
      was effective and methysergide and cyproheptadine were ineffective as antagonists
      of S-MDMA-induced hypermotility. In other systems, methiothepin has been found to
      be a good antagonist at 5-HT1B receptors where methysergide and cyproheptadine
      are ineffective. The 5-HT2 antagonist ritanserin was ineffective in blocking S
      MDMA-induced hypermotility. However, ritanserin, methysergide, and cyproheptadine
      partially reversed the S-MDMA-induced suppression of investigatory responding,
      suggesting a contribution of 5-HT2 receptor activation to this component of the
      behavioral response to S-MDMA. This study indicates that S-MDMA produces a
      characteristic form of locomotor hyperactivity in rats that depends upon
      activation of 5-HT1-like receptors, possibly of the 5-HT1B subtype.

PMID- 1358089
TI  - Progressive and selective impairment of IL-3 and IL-4 production by peripheral
      blood CD4+ T-lymphocytes during the course of HIV-1 infection.
AB  - The amounts of interleukin 3 (IL-3), interleukin 4 (IL-4), tumor necrosis factor
      alpha (TNF-alpha), and tumor necrosis factor beta (TNF-beta) were evaluated by
      immunoenzymatic assays in the supernatant of short-term cultures of whole
      mononuclear cells and purified CD4+ T-lymphocytes, obtained from the peripheral
      blood (PB) of 35 HIV-1(+) asymptomatic individuals (stages I-II of the Walter
      Reed Classification), 20 HIV-1(+) symptomatic patients (WR V-VI), and 40 HIV-1(-)
      blood donors. TNF-alpha and TNF-beta production was similar in HIV-1(+)
      asymptomatic individuals, HIV-1(+) symptomatic patients, and HIV-1(-) controls.
      On the other hand, IL-3 and IL-4 production by either whole mononuclear cells or
      isolated CD4+ T-cells was decreased approximately 2-fold (p < 0.01) in HIV-1(+)
      asymptomatic subjects with respect to HIV-1(-) blood donors and was very low or
      almost absent in HIV-1(+) symptomatic individuals. The reduced IL-3 and IL-4
      production in HIV-1-infected subjects correlated not only with the stage of the
      disease, but also with signs of active viral replication in PB cells, monitored
      by gag p24 antigen in plasma and viral isolation from PB mononuclear cells. This
      selective and progressive impairment in IL-3 and IL-4 production by CD4+ T
      lymphocytes of HIV-1-infected subjects may contribute to explain the
      hematopoietic abnormalities and the derangement of the inflammatory/immune system
      characteristic of AIDS.

PMID- 1358091
TI  - Programmed cell death and AIDS: from hypothesis to experiment.
AB  - Here, Jean Claude Ameisen discusses new findings supporting the hypothesis that
      abnormal induction of programmed cell death (PCD) is relevant to AIDS
      pathogenesis. Recent evidence also suggests that the prevention of PCD is a
      factor in oncogenesis. Together, these ideas provide a framework for the
      reinterpretation of cell survival disorders in terms of PCD dysregulation, and
      suggest that in vivo control of cell signalling has wide-ranging therapeutic
      potential.

PMID- 1358090
TI  - The noisy elderly patient: prevalence, assessment, and response to the
      antidepressant doxepin.
AB  - To measure the prevalence of noisy behavior as a nursing problem, a survey of
      head nurses was done in a chronic care hospital to identify patients whose
      vocalizing was frequently disturbing to other patients, staff, or visitors. We
      found 17 patients among the total of 154. Subsequently, the medical records of 13
      surviving subjects were reviewed more exhaustively, and 11 were described as
      disruptive, usually when they were left alone. Of these "lonely" patients, eight
      had a previously documented diagnosis of depression. All were demented.
      Antipsychotic medication had previously been given to all 11 "lonely" patients,
      but had failed to control their disruptive behavior. Empirically, six patients
      were treated with doxepin, and in five, all with a history of previous
      depression, agitation and noisiness diminished. These observations suggest that
      the prevalence rate of disturbingly noisy behavior among long-term
      institutionalized elderly patients is about 11% and that the disturbingly noisy
      patient is often demonstrating depression in conjunction with dementia.

PMID- 1358092
TI  - Effect of somatostatin on prolactin in rainbow trout (Oncorhynchus mykiss)
      pituitary cells in primary culture.
AB  - To study the control of prolactin secretion in fish, an in-vitro technique using
      a monolayer cell culture system of rainbow trout pituitary glands was developed.
      Such secretion was characterized by measurement of both prolactin release and
      prolactin mRNA content using a trout prolactin cDNA as a probe. This cell culture
      technique, already used to study the regulation of gonadotrophin secretion in
      rainbow trout, was further validated by measuring total DNA and protein content.
      Both parameters appeared to be stable after 2 days of culture. Studying the
      effect of somatostatin (SRIF) on prolactin cells indicated that a maximal
      inhibitory effect (62%) was observed after 24 h of treatment. Significant
      inhibition of prolactin release was obtained for SRIF doses ranging from 50 nM to
      1 microM. However, in the same experiment, SRIF was much more potent as an
      inhibitor of growth hormone release. Short-term (< 12 h) incubation with SRIF did
      not induce a significant change in prolactin release, whereas growth hormone
      release was reduced at as early as 1 h after SRIF exposure. SRIF did not have a
      significant effect on total prolactin content or prolactin mRNA levels,
      suggesting the absence of an effect on prolactin synthesis. No increase in the
      magnitude of the inhibitory effect of SRIF was observed when using pituitary
      cells from immature, mature male or mature female trout. When comparing effects
      on primary cultures containing cells from the whole pituitary with a prolactin
      cell-enriched population, SRIF appeared to have the same inhibitory effect on
      prolactin release, supporting a direct action of SRIF on prolactin cells. These
      results provide further support for SRIF being a prolactin-inhibiting factor in
      rainbow trout and acting as a modulator of a dominant stimulatory control of
      prolactin release.

PMID- 1358094
TI  - Benign Localized and Generalized Epilepsies of Early Childhood. Symposium
      proceedings. Bad Kreuznach, Germany, September 1990.

PMID- 1358093
TI  - Significant compatibility does not exist at the HLA-DQB gene locus in couples
      with unexplained recurrent abortions.
AB  - The polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP)
      method was used for both examining compatibility at the HLA-DQB1 gene locus and
      determining HLA-DQ antigen polymorphism in spouses of unexplained recurrent
      abortions. Genomic DNA samples were prepared from peripheral mononuclear cells
      from patient and control couples. Two hundred and thirty base pair fragments of
      the second exon of the HLA-DQB genes were selectively amplified. Amplified DNAs
      were digested with the restriction endonucleases, Fok I, Hae III, Hha I, Rsa I
      and Sau3A I, and subjected to electrophoresis in a polyacrylamide gel. The RFLPs
      showed that habitual aborters and their husbands had neither significantly
      frequent alleles nor shared common alleles at the HLA-DQB locus when compared to
      the control group. Since significant HLA-DQB compatibility was not observed
      between the spouses and unexplained recurrent aborters, in order to determine
      whether or not HLA compatibility is responsible for the genesis of unexplained
      recurrent abortions, it is imperative to further examine the compatibility
      between other HLA gene loci.

PMID- 1358095
TI  - Neurotransmitters in epilepsy. Dedicated to Herbert H. Jasper.

PMID- 1358096
TI  - Early efforts to find neurochemical mechanisms in epilepsy.

PMID- 1358097
TI  - GABA- and glutamate-containing neurons in the thalamus of rats and cats: an
      immunocytochemical study.

PMID- 1358098
TI  - Apparent desensitization to glutamate: possible role in epilepsy.

PMID- 1358099
TI  - Neurotransmitter pharmacology of the epilepsies: discrepancies between animal
      models and human conditions.

PMID- 1358100
TI  - Changes in the levels of glutamate and related amino acids in the intact and
      decorticated rat neostriatum during various conditions associated with
      convulsions.

PMID- 1358101
TI  - Kindling increases brain levels of NAAG and seizures reduce activity of a NAAG
      hydrolyzing enzyme, NAALADase.

PMID- 1358103
TI  - Neurotransmission in rats' spontaneous generalized nonconvulsive epilepsy.

PMID- 1358102
TI  - Synaptic and nonsynaptic determinants of excitability changes in aluminum
      intoxicated rabbit CA1 pyramidal neurons studied in vitro.

PMID- 1358104
TI  - Modulatory role of GABA receptor subtypes and glutamate receptors in the
      anticonvulsant effect of barbiturates.

PMID- 1358105
TI  - Effects of benzodiazepine receptor ligands with different intrinsic activities on
      seizures induced by inhibition of GAD.

PMID- 1358106
TI  - Experimental animal models of epilepsy: classification and relevance to human
      epileptic phenomena.

PMID- 1358107
TI  - Biology of the chicken MHC (B complex).
AB  - The major histocompatibility complex (MHC) of chicken is the B complex,
      originally described as a blood group system. Its three classes of cell membrane
      antigens have been clearly defined by serological, histogenetic, biochemical, and
      molecular biological methods. Two of these classes are homologous to classes I
      and II of mammals (B-F and B-L respectively), while the third--B-G antigen--has
      not so far been detected in mammals. The possible role of this antigen is
      discussed. The genes of the MHC play important roles in the regulation of immune
      response, disease resistance, and regression of Rous sarcomas.

PMID- 1358109
TI  - Biological role of helper T-cell subsets in helminth infections.

PMID- 1358108
TI  - Murine CD4+ T-cell subsets generated by antigen-independent and dependent
      mechanisms.

PMID- 1358110
TI  - Evidence for functional subsets of CD4+ and CD8+ T cells in human disease:
      lymphokine patterns in leprosy.

PMID- 1358111
TI  - T-cell subsets in experimental allergic encephalomyelitis: interactions between
      the immune and neuroendocrine systems in the regulation of their activity.

PMID- 1358112
TI  - Postthymic differentiation of CD4 T lymphocytes: naive versus memory subsets and
      further specialization among memory cells.

PMID- 1358113
TI  - Interference of substrate quenching with the kinetics of placental peptidases.
AB  - The study was undertaken to clarify the putative presence and influence of
      substrate inhibition and substrate quenching on the kinetic analysis of placental
      peptidases using naphthylamide substrates in a fluorometric assay. Using the
      appropriate naphthylamide substrates, we analysed microsomal alanine
      aminopeptidase (EC 3.4.11.2) and angiotensinase A (EC 3.4.11.7) in the presence
      or absence of inhibitors (1,10'-phenanthroline, EDTA) or activators (calcium) in
      the human and rat placenta. All substrates were shown to quench the fluorescence
      of the enzymatically released unspecific moiety. Since Michaelis-Menten-derived
      kinetic equations do not include quenching phenomena, we deduced a mathematical
      model integrating enzyme kinetics and quenching kinetics, thereby allowing
      simultaneous analysis of both processes from the same raw data. Curves derived
      from this expanded kinetic model fitted significantly better to velocity data
      than those derived from Michaelis-Menten-equation. According to the presented
      data, we assume that substrate inhibition for both enzymes, as previously
      proposed in the literature, in contrast may be due to formerly unconsidered
      substrate quenching. The presented kinetic model could serve as a useful tool in
      the study of putative physiological substrates of the investigated placental
      peptidases, characterizing the physiologic substrates by their competitive
      interaction with the synthetic naphthylamides. Additionally, this model may not
      only be important in fluorometric analysis of peptidases, but also of other
      enzymes which are analysed fluorometrically with synthetic substrates.

PMID- 1358114
TI  - Aluminium administered in drinking water but not in the diet influences biopterin
      metabolism in the rodent.
AB  - To investigate the neurotoxic effects of aluminium (Al) Al was administered: 1)
      in the diet of the rat (30 mg Al/kg body weight for 6 weeks); 2) as a suspension
      of aluminium acetate in drinking water of the rat for 3 months and 3) in a long
      term study in the mouse in which aluminosilicates were incorporated into a
      pelleted diet (1035 mg/kg of food over 23 months). In the latter treatment,
      increased Al was combined with a reduction in calcium and magnesium; a treatment
      designed to increase absorption of Al into the body. Administration of Al in the
      drinking water significantly reduced total brain biopterins and BH4 synthesis.
      However, no significant affect of Al in the diet on total biopterins or BH4
      synthesis was found either in the rat or in the long-term study in the mouse. In
      addition, in the mouse no significant effects of the Al diet on levels of
      noradrenaline, serotonin, dopamine, 5-HIAA or CAT could be demonstrated. Hence,
      the occurrence of brain alterations may depend on the Al species present and the
      method of administration. Al salts in drinking water may increase brain tissue
      levels compared with the administration of a more insoluble species. Since
      alterations in biopterin metabolism are also a feature of Alzheimer's disease
      (AD) these results support the hypothesis that Al in the water supply may be a
      factor in AD.

PMID- 1358115
TI  - Benzodiazepine antagonists. An update of their role in the emergency care of
      overdose patients.
AB  - The benzodiazepine antagonist flumazenil is a very valuable tool in the diagnosis
      and treatment of intoxications in which benzodiazepines are involved. In case of
      a positive response, patients will regain consciousness immediately, thus
      verifying the diagnosis and making a brief history possible to identify other
      drugs that might be involved. Moreover, invasive diagnostic and therapeutic
      procedures like gastric lavage, lumbar puncture, mechanical ventilation, etc.,
      may then be unnecessary. In cases of pure benzodiazepine overdose a single
      injection of flumazenil 0.2mg should be given, followed by individually titrated
      increments of 0.1 mg/min until the patient is awake and responsive. In these
      cases a total dose of 2mg is usually sufficient. Higher doses of flumazenil may
      be necessary in cases of combined drug overdose. Because of its high therapeutic
      index, the administration of flumazenil is usually not accompanied by serious
      adverse effects. Benzodiazepine withdrawal syndromes characterised by transient
      anxiety and depression can occur, but the incidence is low. Increases of blood
      pressure and heart rate due to a release of catecholamines are possible, which
      might endanger patients with cardiovascular diseases. In severe cases, seizures
      have been observed which usually respond well to small doses of benzodiazepine
      agonists. In all cases of successful treatment it should be remembered that the
      effect of flumazenil deteriorates after 1 to 2h, which usually leads at first to
      resedation. In these patients additional bolus injections or a continuous
      infusion (0.1 to 0.5 mg/h) may be necessary. The effectiveness of flumazenil in
      cases of alcohol (ethanol) poisoning is questionable and should be further
      investigated.

PMID- 1358116
TI  - Distributions and colocalization of neuropeptide Y and somatostatin in the
      goldfish brain.
AB  - The distributions of single- and double-labelled neuropeptide Y- (NPY-) and
      somatostatin-immunoreactive (SOM-IR) perikarya and processes were determined in
      the goldfish brain using immunoperoxidase and immunofluorescence techniques,
      respectively. In double-labelled material, it was evident that although these two
      peptides showed markedly similar distributions, they were colocalized in very few
      instances. A high degree of colocalization of NPY and SOM was noted in the
      neurons of the ventrolateral telencephalon (VI), the entopenduncular nucleus (NE)
      and, to a lesser extent, in the dorsocentral nucleus of the telencephalon (Dc).
      In Vl and NE, neurons showing NPY-IR displayed SOM-IR and vice versa. The only
      other instance of colocalization was that noted in the brainstem, where SOM and
      NPY were colocalized in the large cell bodies of the medial column of the vagal
      motor complex. Single-labelled SOM- and NPY-IR neurons shared a very similar
      distribution in various nuclei in the diencephalon and in the optic tectum.
      Colocalization was also noted within fibers throughout many nuclei of the
      telencephalon and within fibers innervating the swim bladder, one of the
      peripheral organs to which neurons of the medial column of the vagal motor
      complex project. Processes in the torus semicircularis and vagal lobe showed
      single-labelled immunoreactivity for both SOM and NPY in distinct laminar
      patterns. Large single-labelled SOM-IR terminals appeared to form pericellular
      baskets in the eminentia granularis of the cerebellum. Single-labelled NPY- or
      SOM-IR fibers were also found in the secondary gustatory nucleus and tract, the
      facial lobe, descending trigeminal tract, reticular formation and spinal cord. As
      in mammalian species, select groups of neurons in teleosts colocalize the
      neuropeptides SOM and NPY.

PMID- 1358117
TI  - D1-receptor antagonists: comparison of [3H]SCH39166 to [3H]SCH23390.
AB  - A radiolabeled form of the benzonaphthazephine, SCH39166 was used to characterize
      the binding of this D1 antagonist in cortex, and an autoradiographic comparison
      of the localization of [3H]SCH39166 to [3H]SCH23390 (D1 antagonist and forerunner
      of SCH39166) binding was performed. The Kd for [3H]SCH39166, calculated from
      dissociation and association rate constants (1.09 nM), was comparable to the Kd
      value derived from Scatchard analyses of saturation data (1.74 nM). [3H]SCH39166
      binds to brain tissue in a saturable manner with high affinity and low non
      specific binding. Inhibition of [3H]SCH39166 binding by dopaminergic and
      serotonergic agents supports the hypothesis that this is indeed a D1-specific
      compound with little overlap onto serotonin (5-HT) receptors. The affinity of
      [3H]SCH39166 for 5-HT2 and 5-HT1c receptors is at least an order of magnitude
      lower than the affinity of [3H]SCH23390 for these same receptor sites.
      Quantitative autoradiographic analysis of [3H]SCH39166 and [3H]SCH23390 binding
      indicates high D1-receptor density in the caudate-putamen, nucleus accumbens,
      olfactory tubercle, substantia nigra and entopeduncular nucleus. Low levels of
      binding (not significantly above background) were detected with [3H]SCH39166 in
      lamina IV of the cortex and in choroid plexus; areas which had significant
      [3H]SCH23390 binding and are known to have a high density of 5-HT (5-HT2 and 5
      HT1c respectively) receptors.

PMID- 1358118
TI  - Large artery compliance in essential hypertension. Effects of calcium antagonism
      and beta-blocking.
AB  - This study used 2D Doppler flowmetry to assess the effects on peripheral
      hemodynamics of effective treatment with nicardipine or atenolol in 40 patients
      with mild or moderate essential hypertension. Two groups of 20 patients received
      treatment with nicardipine or atenolol, respectively, for 8 months. Consequently,
      those patients considered to be responders (blood pressure less than 150/90 mm
      Hg) were monitored for another 4 weeks after the therapy was suspended in order
      to determine whether the changes, if any, in arterial compliance persisted.
      Following the 8-month therapy, four patients from each group were excluded from
      the study because of unsatisfactory blood pressure levels. After the treatment,
      there was a decrease in blood pressure in both groups (P less than .01). In the
      nicardipine group, there was a significant increase in diameter and compliance (P
      less than .01), whereas pulse wave velocity and resistance decreased (P less than
      .01). In the atenolol group, these parameters did not change significantly. After
      therapy was ended, blood pressure returned to baseline values in both groups.
      However, in the nicardipine group, the observed improvement in forearm
      hemodynamics persisted. This result may indicate that nicardipine is able to
      induce a regression of functional and/or structural changes in the large arteries
      of hypertensive patients.

PMID- 1358120
TI  - Cholinergic mechanisms in physical dependence on barbiturates, ethanol and
      benzodiazepines.
AB  - The aim of this review is to summarize the effects of acute and chronic treatment
      with barbiturates, ethanol and benzodiazepines on cholinergic mechanisms in the
      brains of experimental animals. A single dose of each of these substances reduces
      the turnover of ACh in the brain. Long-term treatment has the opposite effect;
      complicated interactions including decreased content of ACh are induced.
      Barbiturates have been shown to bind stereospecifically to muscarinic and
      nicotinic receptors in the brain, but this has not been observed for ethanol or
      the benzodiazepines. The effects on the cholinergic system are affected by the
      length of treatment and choice of treatment regimen. No effect on cholinergic
      parameters, such as muscarinic receptors, in the brain is observed on withdrawal
      of ethanol or barbiturate treatment when the animals are still tolerant towards
      the substances. The increase in the number of muscarinic receptors observed in
      several brain regions on withdrawal is seen as a sign of cholinergic
      supersensitivity. The number of receptors returns to normal when abstinence
      convulsions have occurred. The assumption of a cholinergic influence is supported
      by the finding that atropine, given as a single dose on the day of withdrawal of
      barbital, can prevent the muscarinic receptor changes. Furthermore, long-term
      barbital or ethanol treatment can induce permanent persistent changes in the
      cholinergic system in the brain. Cognitive defects and a significant permanent
      reduction in the content of ACh can be measured in rats which have had long-term
      barbital treatment. Similarly, a reduced number of muscarinic receptors has been
      measured in different brain regions of chronic alcoholics. Accumulating data
      support the role of the cholinergic system in expressing symptoms of physical
      dependence on barbiturates, ethanol and benzodiazepines as well as in the
      permanent long-term effects observed after end of treatment.

PMID- 1358119
TI  - Pharmacologic properties of (-)-3PPP (preclamol) in man.
AB  - The dopamine (DA) autoreceptor agonist (-)-3PPP (preclamol) was tested in male
      schizophrenic volunteers for safety. The drug was administered intramuscularly in
      a single rising dose design, crossed with a similar "rising dose" placebo period;
      all evaluations and raters were blind to drug or placebo administration.
      Pharmacokinetic, endocrine, safety, and mental status outcome measures were
      completed before and after each single dose of drug or placebo. Pharmacokinetic
      analysis showed blood levels between 200-500 pmoles/ml after the intramuscular
      drug doses of 30-40 mg. Drug half life is 2-2.5 hrs. Growth hormone (GH) levels
      were elevated in a linear fashion to the 30 mg dose; whereafter, the drug failed
      to affect GH at all. All safety evaluations were negative, including any untoward
      effects on the major organ systems. After single dose drug administration,
      evidence of antipsychotic action occurred in two of the four subjects. This study
      suggests that (-)-3PPP/preclamol is a safe drug for study in the treatment of
      schizophrenia and may have antipsychotic efficacy.

PMID- 1358122
TI  - Typical and atypical neuroleptics antagonize MK-801-induced locomotion and
      stereotypy in rats.
AB  - The effects of typical and atypical neuroleptics on MK-801-induced locomotor
      activity and stereotyped sniffing were tested. Pretreatment with the typical
      neuroleptic haloperidol (0.01, 0.05, 0.1, 0.5 mg/kg SC) and the dopamine D2
      receptor selective antagonist eticlopride (0.005, 0.01, 0.05 mg/kg SC) each
      resulted in significant and dose-dependent reductions of locomotor activity and
      sniffing. The atypical neuroleptic clozapine (1.0, 5.0, 10.0 mg/kg SC) was
      somewhat unique in that all doses reduced locomotor activity, but only the
      highest dose (10.0 mg/kg) significantly reduced sniffing. The data support a
      functional interaction between glutamate and dopamine systems, and suggest that
      the behavioral activation associated with MK-801 may represent a valid model for
      detecting potential therapeutic agents in the treatment of schizophrenia. The
      data should be viewed as preliminary, however, until neuroleptics are
      characterized in other glutamate-based models that minimized or exclude the
      possible influence of nonspecific motor effects.

PMID- 1358121
TI  - Interaction between glutamatergic and dopaminergic tone in the nucleus accumbens
      of mice: evidence for a dual glutamatergic function with respect to psychomotor
      control.
AB  - The rotation induced by a unilateral injection of the competitive NMDA receptor
      antagonist AP-5 was studied in mice with different tone in the central
      dopaminergic systems. AP-5 induced contralateral rotation in monoamine-depleted
      mice and in monoamine-depleted mice treated with a dopamine D-1 receptor agonist.
      In contrast, AP-5 induced predominantly ipsilateral rotation in monoamine
      depleted mice treated with a mixed D-1/D-2 or a D-2 selective dopamine agonist
      and in mice with intact monoaminergic systems.

PMID- 1358124
TI  - The 2nd Conference on Valve and Valvular Diseases. Tokyo, July 13-14, 1991.

PMID- 1358123
TI  - Neurochemical evidence for a neuronal GABAergic system in the rat sympathetic
      superior cervical ganglion.
AB  - Some characteristics of gamma aminobutyric acid (GABA) uptake and release in rat
      superior cervical ganglion (SCG) were investigated. Kinetic analysis of GABA
      uptake indicated the existence of both high affinity (Km = 18.6 microM) and low
      affinity (Km = 485 microM) uptake systems. 3H-GABA influx was decreased by
      inhibitors of glial (beta-alanine), neuronal (2,4-diaminobutyric acid, DABA), or
      glial and neuronal GABA uptake (nipecotic acid). 3H-GABA efflux was elicited by
      K+ depolarization in a dose-dependent manner, an effect unaltered by severing the
      preganglionic nerve fibers. Superfusion of SCG explants with DABA or beta-alanine
      resulted in increased 3H-GABA efflux from tissue, an effect amplified by the
      absence of calcium in the superfusion medium. 3H-GABA loading in the presence of
      DABA, but not in the presence of beta-alanine, resulted in abolition of K(+)
      elicited 3H release. At 20 mM, but not at 50 mM K+, the release of 3H-GABA was
      inhibited by replacing Ca2+ by Mg2+ and by adding EGTA, or by incubating SCG in
      the presence of the Ca(2+)-channel blocker verapamil. Veratrine evoked GABA
      release in Ca(2+)-independent manner. None of several putative SCG autacoids or
      agonists (nicotine, muscarine, norepinephrine, dopamine, serotonin, baclofen,
      muscimol) significantly modified GABA release.

PMID- 1358125
TI  - The importance of serotonin-dopamine interactions in the action of clozapine.
AB  - Clozapine has an affinity for the dopamine (DA) D2 receptor which is relatively
      weak but is in line with its average clinical dose when compared with typical
      neuroleptic drugs. A few atypical antipsychotic drugs may have high absolute
      affinities for the D2 receptor, but most are weak D2 blockers. The atypical
      antipsychotic drugs also differ from the typical antipsychotic drugs by a
      relatively high affinity for the serotonin (5-HT2) receptor. This is evident on
      both in vitro and in vivo binding to cortical 5-HT2 receptors. The atypical
      antipsychotics are best distinguished from the typical antipsychotics on the
      basis of the relationship between strong 5-HT2 and weak D2 affinities. High D1
      receptor binding is not characteristic of the group of atypical drugs. A new
      group of putative atypical antipsychotic drugs with high affinities for 5-HT2
      compared to D2 receptors is under study.

PMID- 1358127
TI  - General pharmacology of clozapine.
AB  - Clozapine shows neuroleptic-like inhibition of locomotor activity and conditioned
      avoidance responding in rodents, although tolerance develops on repeated
      treatment. EEG-based studies show strong arousal-inhibiting activity of clozapine
      as well as neuroleptic-like effects on both caudate spindle duration and rat
      sleep-waking patterns. Effects such as apomorphine blockade, catalepsy and strong
      increases of plasma prolactin levels are not seen, however, and chronic treatment
      does not lead to dopamine D2 receptor supersensitivity. Binding studies show
      clozapine's highest affinities to be for dopamine D4, 5-HT1C, 5-HT2, alpha 1,
      muscarinic and histamine H1 receptors, but moderate affinity is also seen for
      many other receptor subtypes. Microdialysis studies indicate a preferential
      interaction with striatal D1 receptors, whereas autoradiographical studies
      indicate upregulation of D1 and downregulation of 5-HT2 receptors after chronic
      clozapine. Clarification of the mechanisms underlying clozapine's special
      attributes is often hampered by a failure to examine compounds which show a close
      chemical relationship to clozapine, but which produce extrapyramidal side-effects
      in man, such as clothiapine, loxapine and amoxapine.

PMID- 1358126
TI  - PET analysis indicates atypical central dopamine receptor occupancy in clozapine
      treated patients.
AB  - D1 and D2 dopamine (DA) receptor occupancy was determined by PET in the basal
      ganglia of drug-treated schizophrenic patients. In 22 patients treated with
      classical neuroleptics at conventional doses, the average D2 occupancy was 78%
      (s.d. 6%). In five patients treated with the prototype atypical antipsychotic
      drug clozapine, a lower D2 occupancy of 48% (s.d. 11%, P less than 0.01) was
      found. Accordingly, clozapine is 'atypical' with respect to the striatal D2 DA
      receptor occupancy induced in patients. No obvious D1 DA receptor occupancy was
      induced by the classical neuroleptics haloperidol or sulpiride. The thioxanthene
      flupenthixol induced a 36-44% D1 occupancy in individual patients. In four
      patients treated with clozapine the D1 occupancy was 38-52%.

PMID- 1358128
TI  - Clinical management of clozapine patients in relation to efficacy and side
      effects.
AB  - Medical charts of 480 schizophrenic in-patients (581 treatments) were analysed to
      evaluate the efficacy and side-effects of clozapine. Clozapine treatment lasted
      for mean 49 (s.d. 38) days. Of the sample, 11.0% showed worsening or no change,
      31.5% slight improvement, 53.0% marked improvement and 4.5% almost total
      reduction of symptoms. At least one major side-effect occurred in 68.0% of
      patients. A combination of clozapine with classical neuroleptics,
      antidepressants, benzodiazepines or lithium is tolerated by most patients, but
      increases the incidence of some side-effects. Clozapine treatment had to be
      discontinued because of severe side-effects in 8.6% of patients. In 81
      schizophrenic out-patients, clozapine significantly reduced the days of in
      patient treatment and number of hospital readmissions. Two patients developed
      leucopenia but had no complications after clozapine withdrawal. This study
      indicates a satisfactory benefit/risk ratio and compliance in most of the
      patients.

PMID- 1358129
TI  - Clinical aspects and distribution of immunologically active cells in the nasal
      mucosa of patients with nasal polyps after endoscopic sinus surgery and treatment
      with topical corticosteroids.
AB  - Clinical parameters of 72 patients who were operated upon for nasal polyps were
      evaluated as well as biopsy specimens of the mucosa of the middle and inferior
      turbinates of 41 of these patients. Biopsies were taken at the time of endoscopic
      sinus surgery (ESS), after 6 months and after 1 year in 23 patients. During the
      follow-up period the patients were treated with topical corticosteroids
      (budesonide). At the time of ESS significantly more CD8+ (suppressor/cytotoxic)
      cells than CD4+ (helper/inducer) cells were found in the middle and inferior
      turbinates. At 6 months significantly more CD4+ cells were found than at the time
      of ESS, whereas at 1 year the number of CD4+ cells had decreased and was lower
      than at 6 months. These data support the theory that the occurrence of nasal
      polyps is associated with T-cell-dependent disturbances. Clinical evaluation
      revealed that most of the patients with chronic airway obstruction had better
      pulmonary functions postoperatively or required less medication for lung disease.
      These findings show that ESS combined with topical corticosteroids has a positive
      effect on upper and lower respiratory tract pathology.

PMID- 1358130
TI  - An application of a simple method for the preparation of bacterial DNA.

PMID- 1358131
TI  - Presynaptic inhibition of miniature excitatory synaptic currents by baclofen and
      adenosine in the hippocampus.
AB  - Presynaptic inhibition of neurotransmitter release is thought to be mediated by a
      reduction of axon terminal Ca2+ current. We have compared the actions of several
      known inhibitors of evoked glutamate release with the actions of the Ca2+ channel
      antagonist Cd2+ on action potential-independent synaptic currents recorded from
      CA3 neurons in hippocampal slice cultures. Baclofen and adenosine decreased the
      frequency of miniature excitatory postsynaptic currents (mEPSCs) without
      affecting the distribution of their amplitudes. Cd2+ blocked evoked synaptic
      transmission, but had no effect on the frequency or amplitude of either mEPSCs or
      inhibitory postsynaptic currents (IPSCs). Inhibition of presynaptic Ca2+ current
      therefore appears not to be required for the inhibition of glutamate release by
      adenosine and baclofen. Baclofen had no effect on the frequency of miniature
      IPSCs, indicating that gamma-aminobutyric acid B-type receptors exert distinct
      presynaptic actions at excitatory and inhibitory synapses.

PMID- 1358132
TI  - Effects of nilvadipine on the cardiovascular responses to tracheal intubation.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of nilvadipine given orally in
      attenuating the hypertensive response to laryngoscopy and intubation. DESIGN:
      Controlled, randomized, double-blind study. SETTING: Induction of anesthesia for
      elective surgery at a university hospital. PATIENTS: Thirty normotensive patients
      (ASA physical status I) undergoing elective surgery were divided into three
      groups of ten patients each. INTERVENTIONS: Either 2 mg of nilvadipine, 4 mg of
      nilvadipine, or a placebo (control) was administered orally 90 minutes before
      induction of anesthesia. Anesthesia was induced with thiopental sodium 5 mg/kg
      intravenously, and tracheal intubation was facilitated with vecuronium 0.2 mg/kg.
      During anesthesia, ventilation was assisted or controlled with 1% enflurane and
      50% nitrous oxide (N2O) in oxygen. Laryngoscopy lasting 30 seconds was attempted
      2 minutes after administration of thiopental sodium and vecuronium. MEASUREMENTS
      AND MAIN RESULTS: Patients receiving the placebo showed a significant increase in
      mean arterial pressure (MAP) and heart rate associated with tracheal intubation.
      The increase in MAP following tracheal intubation was significantly lower in
      nilvadipine-treated patients than in the control group (p less than 0.05).
      However, neither dose of nilvadipine attenuated the tachycardic response to
      intubation. CONCLUSIONS: Oral administration of nilvadipine before induction of
      anesthesia is a simple and practical method for attenuating pressor response to
      laryngoscopy and tracheal intubation after standard elective induction under
      additional 1% enflurane-N2O anesthesia.

PMID- 1358134
TI  - Effect of esmolol on hemodynamics and intraocular pressure response to
      succinylcholine and intubation following low-dose alfentanil premedication.
AB  - STUDY OBJECTIVE: To determine the effectiveness of esmolol hydrochloride
      (Brevibloc) as an additional adjunct to low-dose alfentanil premedication in
      controlling the hemodynamic response [heart rate (HR), mean arterial pressure
      (MAP), and intraocular pressure (IOP)] to succinylcholine and endotracheal
      intubation. DESIGN: Randomized, double-blind, placebo-controlled, prospective
      study. SETTING: Ambulatory gynecologic surgery at a university medical center.
      PATIENTS: Twenty ASA physical status I and II female patients scheduled for
      outpatient laparoscopy under general anesthesia. INTERVENTIONS: All patients
      received alfentanil 10 micrograms/kg as a preoperative medication 4 minutes prior
      to induction of anesthesia. Study patients (n = 10 in each group) received either
      esmolol 1.5 mg/kg or a placebo (normal saline) 30 seconds prior to induction (210
      seconds after alfentanil and 90 seconds prior to endotracheal intubation).
      Anesthesia was induced with thiopental sodium 5 mg/kg and succinylcholine 1
      mg/kg. Postintubation, 70% nitrous oxide, 30% oxygen, and 1% isoflurane were
      administered. MEASUREMENTS AND MAIN RESULTS: Time of study drug administration
      was defined as time zero. Measurements of HR, MAP, and IOP were made at baseline
      (patient awake) and at each minute from minutes 1 through 6 after administration
      of the study drug (time zero). Analysis of variance was used to analyze the data,
      with a value of p less than 0.05 considered significant. Esmolol 1.5 mg/kg was
      found to blunt the maximum increase in HR but not MAP or IOP following low-dose
      alfentanil premedication. CONCLUSIONS: In an eye patient with coronary artery
      disease, or in any patient in whom tachycardia may be detrimental, esmolol may be
      a useful adjunct in combination with low-dose alfentanil to attenuate the
      increase in HR due to laryngoscopy and endotracheal intubation.

PMID- 1358133
TI  - Partial attenuation of the cardiovascular responses to tracheal intubation with
      oral nisoldipine.
AB  - STUDY OBJECTIVE: To evaluate the efficacy and safety of nisoldipine given orally
      in attenuating the cardiovascular responses to laryngoscopy and tracheal
      intubation. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING:
      Induction of anesthesia for elective surgery at a university hospital. PATIENTS:
      Thirty normotensive patients (ASA physical status I) undergoing elective surgery
      were assigned to one of three groups; placebo, nisoldipine 5 mg, or nisoldipine
      10 mg. Each group consisted of ten patients. INTERVENTIONS: Either 5 mg of
      nisoldipine, 10 mg of nisoldipine, or a placebo was administered orally 2 hours
      before induction of anesthesia. Anesthesia was induced with thiopental sodium 5
      mg/kg intravenously, and tracheal intubation was facilitated with vecuronium 0.2
      mg/kg. During anesthesia, ventilation was assisted or controlled with 1%
      enflurane and 50% nitrous oxide in oxygen. Laryngoscopy lasting 30 seconds was
      attempted 2 minutes after administration of thiopental sodium and vecuronium.
      MEASUREMENTS AND MAIN RESULTS: Patients receiving the placebo showed a
      significant increase in mean arterial pressure associated with tracheal
      intubation. These increases following tracheal intubation were significantly
      reduced in patients receiving nisoldipine 10 mg compared with patients receiving
      the placebo (p less than 0.05). CONCLUSIONS: Oral administration of nisoldipine
      before induction of anesthesia is a simple, practical, and safe method for
      attenuating pressor response to laryngoscopy and tracheal intubation.

PMID- 1358136
TI  - Bioavailability and analgesic effect of sustained release cetobemidone capsules
      in cancer patients with chronic pain of malignant origin.
AB  - Ever since its introduction in 1952, Ketogan has consisted of a combination of
      the opioid cetobemidone and a spasmolytic drug, A29, in the ratio of 1:5. Its
      main limitations are the relatively short duration of action and an apparent
      ceiling effect due to A29. We therefore developed a cetobemidone formulation with
      sustained release properties (cetobem. s.r.). Forty-seven patients with advanced
      cancer with moderate/severe pain, treated with regular doses of Ketogan tablets
      took part in an open phase 1 type pharmacologic/toxicologic study comparing
      Ketogan tablets and cetobem. s.r. The patients spent at least 4 days in the
      department. After evaluation during 12 h with Ketogan tablets (3-4 dosing
      intervals), a loading phase lasting for 36 h with cetobem. s.r. given twice/24 h
      (total dose of Ketogan tablets per 24 h divided by 2), and synchronous reduction
      of the dose of Ketogan tablets, a similar evaluation period of 12 h was performed
      when on treatment with cetobem. s.r. alone. Comparison of data from the two
      observation periods showed the following: Average relative bioavailability 0.77
      SD 0.28. Only 2 patients were remedicated before 12 h when on cetobem. s.r.
      Duration of action mean 11.9 h, SD 0.3 h. There was no significant difference
      between Ketogan tablets and cetobem. s.r. periods concerning 'time with no pain'.
      Side-effects were few. The only significant difference was dry mouth being more
      severe during the tablet period. Vital signs were unaffected by treatment. It is
      concluded that cetobem. s.r. can be given every 12 h to cancer patients with
      chronic pain with satisfactory analgesic effect, a very modest change in side
      effect profile and no significant effects on vital signs when substituting
      cetobem. s.r. for Ketogan tablets in equal daily doses.

PMID- 1358135
TI  - Propofol in patients susceptible to malignant hyperthermia: a case report and
      review of the literature.
AB  - Propofol is an intravenous (IV) drug recently introduced into the United States
      for induction and maintenance of anesthesia. In spite of extensive laboratory
      evaluation, it is not possible to predict all the potential side effects that
      might be associated with a new drug. Because malignant hyperthermia (MH) remains
      a serious and potentially life-threatening complication of anesthesia, all new
      anesthetic drugs should be considered potential triggering drugs until proven
      otherwise. We report the use of IV propofol for the induction and maintenance of
      general anesthesia in an MH patient and review the literature on this subject.

PMID- 1358138
TI  - [XXX annual reunion of the Spanish Society of Otorhinolaryngology and Cervico
      Facial Pathology. Madrid, Spain, 11-14 November 1992. Abstracts].

PMID- 1358137
TI  - 1st International Workshop on Pore-Forming Toxins and their Role in the
      Competition among Different Organisms. Trento, Italy, 26-29 September 1991.

PMID- 1358139
TI  - Central nervous system side-effects of antihistamines in schoolchildren.
AB  - There are no studies available in the literature on the effects of classical
      antihistamines on the central nervous system (CNS) in children. Clinical studies
      indicate that somnolence occurs more often with classical antihistamines than
      with placebo. There is no difference in inducing somnolence in children between
      placebo and astemizole or terfenadine, two new antihistamines that have
      thoroughly been shown to have no sedative effect greater than placebo in adults.
      A double-blind, cross-over trial investigating the CNS-effects of astemizole and
      chlorpheniramine in schoolchildren failed to show a negative effect of either of
      these drugs on performance.

PMID- 1358140
TI  - Levocabastine: a new topical approach for the treatment of paediatric allergic
      rhinoconjunctivitis.
AB  - Levocabastine is a novel H1-receptor antagonist for topical use, which is being
      investigated in allergic rhinitis (nasal spray) and conjunctivitis (eye drops).
      Its anti-allergic effects have been demonstrated in nasal and ocular provocation
      tests. Clinical studies have been performed in 1,363 patients with allergic
      rhinitis and 1,218 patients with allergic conjunctivitis, comparing levocabastine
      mainly to placebo and cromoglycate. Levocabastine was effective when used at a
      dose of 2 sprays per nostril or 1 drop per eye twice daily, which if necessary
      can be increased up to four times daily. Levocabastine was superior to placebo in
      alleviating symptoms such as sneezing, itchy nose, runny nose, itchy eyes, red
      eyes and lacrimation. In global evaluations some 60% of patients had good to
      excellent results with the nasal spray and some 75% with the eye drops.
      Levocabastine was shown to be as good or even slightly better than cromoglycate.
      Onset of action was fast, with 73% of patients reporting symptom relief within 30
      min after administration of levocabastine nasal spray. Adverse experiences were
      similar in type and incidence with levocabastine, cromoglycate and placebo, for
      nasal spray as well as eye drops. The most frequent complaints were nasal and
      ocular irritation, respectively, with a similar incidence for the three drugs.
      Limited data are available in children so far, but they indicate response rate
      and adverse-experience profile to be similar to what was observed in adults.
      Levocabastine, thus, is an interesting new antihistamine available for topical
      use in allergic rhinoconjunctivitis. It has been extensively evaluated in adults,
      and preliminary data indicate that it can also be useful in allergic children.

PMID- 1358141
TI  - New strategies for the prevention and treatment of allergic rhinitis in children.
AB  - Allergic rhinitis (AR) is a very common disease in children, often underdiagnosed
      and with underestimated complications. Its prevalence has increased during the
      last years, due to changes in environmental factors. The therapeutic strategy
      will include prevention by identification and eviction of the main allergens,
      associated to pharmacological therapy. Among antirhinitic drugs, the new
      generation of non-sedative specific antihistamines represent the main choice. We
      report our own experience with astemizole, one of these new antihistamines which
      confirms that astemizole is an effective and safe drug for the management of AR
      in children.

PMID- 1358142
TI  - The role of ecotoxicology in the assessment of human exposure to chemical
      substances.
AB  - In the late 1970s new legislation was established in many industrialized
      countries in order to protect the environment. This has led to the definition of
      a new branch of science: ecotoxicology. The development of predictive approaches
      for the hazard assessment of chemical substances has given increased relevance to
      exposure evaluation. This paper discusses the problems related to the
      environmental distribution and fate of chemicals and their potential use in the
      assessment and prediction of exposure of the general population, through air,
      drinking water and food. Collaboration between toxicologists and ecotoxicologists
      is urged to improve our capability to manage chemicals.

PMID- 1358143
TI  - Determination of heavy metals in human liver.
AB  - The levels of Cr (2.49 +/- 0.89 ppm), Mn (5.08 +/- 1.60 ppm), Ni (1.81 +/- 0.95
      ppm) and Pb (4.43 +/- 3.12 ppm) were measured in dessicated liver from 44 cases
      of sudden traumatic death considered as representative of the general population
      in our area, after ruling out the presence of any underlying disease. Atomic
      absorption spectrophotometry and electrothermal atomization was carried out after
      hot, acid digestion, of the dessicated samples. After cancelling the influence of
      age and cause of death, a significant, positive correlation between Cr/Mn (P =
      0.0009; R = 0.493) and Cr/Ni (P = 0.0245; R = 0.347) levels was found.

PMID- 1358144
TI  - Arsenic-copper interaction in the kidney of the rat.
AB  - 1. The interaction between As and three toxic metals (Cd, Ni and Pb) and Cu (an
      essential trace metal) in the kidney was investigated in the rat by feeding diets
      containing various concentrations of As whilst maintaining constant
      concentrations of the other elements. After 1, 3, 7 and 15 weeks of feeding,
      metal contents in the renal cortex and medulla, red blood cells and plasma were
      determined by atomic emission spectrometry (ICP-AES). 2. As accumulated in the
      whole kidney, whereas Cu accumulated only in the cortex. Accumulation of Cu was
      found to depend on the feeding period and dietary As concentration. 3. As was
      also accumulated in red blood cells, where saturation was found at 550 micrograms
      As g-1 cells. 4. Although Cd was also accumulated in the cortex, its accumulation
      was independent of the dietary As concentration. Ni and Pb were not detected by
      ICP-AES. 5. Chromatography of the supernatants from cortical homogenates of
      control and As-treated rat kidney suggested that Cu accumulated in renal
      metallothionein (MT). Its accumulation in this fraction was independent of that
      of Cd, indicating that the As-Cu interaction was not a result of MT induction,
      but rather that it might result from altered renal handling of Cu with subsequent
      incorporation into MT.

PMID- 1358145
TI  - Chronic exposure to n-hexane induces changes in nerve-specific marker proteins in
      the distal peripheral nerve of the rat.
AB  - 1. After long-term n-hexane exposure (2000 ppm, 12 h d-1, 6 d week-1, for 24
      weeks), the content of neuron-specific enolase (gamma-enolase), creatine kinase-B
      and beta-S100 protein in the cortex, cerebellum, spinal cord and proximal and
      distal sciatic nerves of rats was determined by enzyme immunoassay. 2. The
      amounts of the three proteins decreased significantly in the distal segment of
      sciatic nerve, whereas they remained unchanged in the brain and proximal sciatic
      nerve. The quantitative decline in these marker proteins in the distal sciatic
      nerve could be related to neurophysiological deficits in the peripheral nerves.
      3. This study indicates that the biochemical changes observed are consistent with
      the clinical and pathological findings of n-hexane neuropathy. These nerve
      specific marker proteins can be used to assess solvent-related peripheral
      neurotoxicity.

PMID- 1358146
TI  - Aspects of orthodox medicines (therapeutic drugs) poisoning in urban Zimbabwe.
AB  - 1. A retrospective study (extending over 10 years, 1980 to 1989 inclusively) of
      hospital admission cases, due to therapeutic drug poisoning was carried out at
      the six main hospitals of Zimbabwe's four cities. 2. The four cities have a total
      population of approximately 4 million. 3. A total of 1061 cases were recorded and
      analysed. This constituted 16.7% of all poisoning admission cases (i.e. the
      fourth biggest cause of poisoning after traditional medicines, household
      chemicals and snake/insect venom). 4. Of the 1061 cases, 31% were aged 21-30
      years, 21.9% were aged 11-20 years, 14.9% were aged under 5 years and 12.8% were
      aged 31-40 years. Those aged over 80 years accounted for only 0.6% of the cases.
      5. The major groups of drugs implicated were: the analgesics, 22% of the total;
      sedatives and hypnotics, 13.2%; antipsychotics, 11.6%; antimalarials, 9.3%;
      antidepressants, 9.0%; antimicrobials, 7.5%; and alcohol, 7.1%. The other drugs
      each accounted for the less than 7%; the least used group were the
      gastrointestinal drugs which formed only 0.6% of the total. Poisoning due to drug
      abuse was cited at 1.3%. Overdose, either accidental or in the course of
      treatment, accounted for 63.5% of the cases. 6. The mortality rate was 3.9% and
      most of the deaths were suicides. 7. Treatment consisted mainly of the
      administration of ipecacuanha in those under 5 years old age and supportive
      therapy in adults. A few cases were given an antidote if it was specifically
      indicated.

PMID- 1358147
TI  - A pattern of acute poisoning in children in urban Zimbabwe: ten years experience.
AB  - 1. A retrospective analysis was performed to evaluate the epidemiology of
      poisoning in children based on admissions to six of Zimbabwe's main urban
      hospitals over a 10-year period from 1980 to 1989 inclusive. 2. A total of 2873
      cases were children aged between 0-15 years. This constituted 47.8% of poisoning
      cases from all age groups (6018) recorded during the study period. 3. All of the
      children (0-15 years) had signs and symptoms of poisoning on admission and,
      depending on their severity, were admitted to a ward or to an intensive care
      unit. A total of 4.9% (141) died. Most of those who died were suicide cases among
      the 11-15 year age group and accidental poisonings among the 0-15 year old group.
      4. The under 0-5 age group constituted the majority of cases (75.4%) in the 0-15
      age group, and most were between 1 and 3 years old. The 6-10 and 11-15 age groups
      formed 12.6% and 12% of the cases, respectively. The sex distribution showed that
      53.1% were male. 5. Most incidences were accidental (93.2%). Suicides and
      parasuicides accounted for 1.9% and there were only two homicides. 6. The
      commonest toxic agents were: household products (27.2%), traditional medicines
      (23.%), venoms from snake bites and insect stings (16%) and therapeutic agents
      (12.4%). Of the therapeutic agents the most frequently implicated were
      antipsychotics 18.9%, analgesics 16.8%, anti-infectives 11.7%, anticonvulsants
      (8.2%) and benzodiazepines (7.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358148
TI  - Individual differences in activity of glutathione peroxidase and catalase studied
      in monozygotic twins discordant for smoking.
AB  - 1. Cigarette smoke contains free radicals. The enzymes glutathione peroxidase
      (GSH-px) and catalase are important parts of the anti-oxidative protecting
      system. 2. Ten pairs of monozygotic twins, who were discordant for smoking, were
      analysed in order to determine their erythrocyte glutathione peroxidase and
      catalase activities and their plasma concentrations of selenium. 3. Analysis of
      variance (ANOVA) revealed that the difference in activities of catalase and
      glutathione peroxidase was much less within pairs than between pairs, indicating
      a large individual variation due to genetic expression or shared environment and
      no major effect from smoking. 4. The plasma selenium levels of the investigated
      twins revealed sufficient intake of selenium to maintain maximal activity of GSH
      px in erythrocytes. The mean +/- s.d. selenium concentration in plasma for
      smokers was 98 +/- 16 micrograms l-1 and for non-smokers 111 +/- 16 micrograms l
      1. There was no correlation between plasma selenium and glutathione peroxidase in
      erythrocytes.

PMID- 1358149
TI  - Sudden infant death syndrome (SIDS) and the toxic gas hypothesis: microbiological
      studies of cot mattresses.
AB  - 1. Fifty infants' mattresses were studied to investigate the occurrence of viable
      fungal and bacterial propagules, with particular reference to Scopulariopsis
      brevicaulis which had been suggested to be implicated in SIDS cases. A total of
      19 SIDS cases mattresses, 1 non-SIDS death, 20 used controls, and 10 new unused
      controls were examined. 2. Differences were found between SIDS and used controls
      in the variety of fungal species isolated and the numbers isolated from fillings;
      bacterial numbers were similar. 3. S. brevicaulis was isolated from only four
      mattresses, three of which were SIDS cases. It was not found in most of those on
      which death had occurred. 4. A number of potentially pathogenic or allergenic
      fungi, including Aspergillus fumigatus, were isolated more frequently from SIDS
      cases mattresses than new or used controls. 5. Scanning electron microscopy of
      mattress covers and fillings showed microbial 'biofilms' in the head areas of all
      SIDS cases examined. This was not seen on other samples. 6. The limited number of
      mattresses studied and the use of unmatched controls precludes the drawing of any
      general conclusions as to the significance of the biofilms or other fungi
      isolated. 7. Reports of the existence of a dimorphism in general growth forms of
      S. brevicaulis were investigated by growing and transferring authentic strains
      between a variety of growth media. 8. No 'slimy' state of this fungus was
      observed and dimorphism was not confirmed.

PMID- 1358150
TI  - Lack of acipimox-digoxin interaction in patient volunteers.
AB  - 1. A study was carried out to find out if digoxin and acipimox interact. 2. Six
      elderly patients on digoxin were each given acipimox 150 mg three daily for a
      week, after informed consent. Digoxin and acipimox plasma concentrations and
      urinary excretion were measured after the first dose of acipimox and after a week
      of treatment. 3. Data were fitted to a one-compartment oral absorption model.
      Areas under the plasma concentration-time curve, plasma and renal clearances, and
      elimination half-life were computed. 4. There was no significant difference in
      digoxin plasma concentrations and kinetic parameters before and after acipimox
      administration. Acipimox kinetics were not affected by the concomitant ingestion
      of digoxin. 5. The patients' clinical condition remained stable during the study.
      6. Thus there was no evidence for an adverse interaction between digoxin and
      acipimox in human subjects under the conditions of this study.

PMID- 1358151
TI  - Persistence of metaldehyde during acute molluscicide poisoning.
AB  - A case is presented in which a 37-year-old man took an overdose of Slugit, liquid
      containing metaldehyde. Significant concentrations were found in his serum and
      urine for several days afterwards. Acetaldehyde and ethanol were not detected.
      The significance of these findings is discussed.

PMID- 1358152
TI  - Determination of amitriptyline in the hair of psychiatric patients.
AB  - A study was conducted on 60 psychiatric patients to evaluate the reliability of a
      drug-exposure screening test based on gas chromatography/mass spectrometry
      analysis of hair samples for amitriptyline, and the possibility of using the hair
      concentrations of amitriptyline to monitor patients' therapeutic compliance. The
      qualitative test was found to be very reliable (sensitivity 93.3%; specificity
      100%; positive and negative predictive values 100 and 93.8%) in assessing the
      consumer status of patients over a period of 2 months before analysis. Hair
      levels of amitriptyline ranged from 0 to 17.21 ng mg-1. A significant
      relationship (r = 0.563; P < 0.002) was found between the hair concentrations and
      the cumulative intake of amitriptyline over the studied period, but was not
      judged close enough to estimate one individual's therapeutic compliance. The
      results are discussed in the light of existing literature.

PMID- 1358153
TI  - Conclusions of the satellite symposium of the Eurotox '91 Congress on Safety
      Aspects of Biotechnology-Derived Drugs.

PMID- 1358154
TI  - A case of porphyria due to carbaryl intoxication.

PMID- 1358155
TI  - Meeting of the British Toxicology Society.

PMID- 1358156
TI  - Flow cytometric characterisation of proliferating cell nuclear antigen using the
      monoclonal antibody PC10.
AB  - Anti-PCNA antibodies have aroused considerable interest recently as potential
      immunohistochemical markers of proliferation for use on clinical samples. PC10 is
      a monoclonal antibody which has been shown to recognise its epitope on formalin
      fixed, paraffin-embedded, archival material. However, whilst PC10 gives the
      expected labelling pattern for growth fraction in normal tissues and some
      tumours, discrepant results have been obtained, for example, in carcinoma of the
      breast. By means of flow cytometry, we have attempted to characterise the
      different staining patterns that can be obtained with PC10. Intact fixed cells
      from proliferative mammalian cultures show 100% labelling, consistent with a
      growth fraction estimate. In contrast, detergent-extracted nuclei show S-phase
      specific staining. Nuclei extracted by treatment of fixed cells with pepsin show
      a different staining pattern again, with many G1 cells weakly stained and
      staining intensity increasing through S-phase into G2. The results demonstrate
      that multiparametric flow cytometry can define the cell populations which label
      with proliferation-related antibodies, such as PC10, under a variety of
      experimental conditions.

PMID- 1358157
TI  - Bone Morphometry 1992, 6th International Meeting. Lexington, Kentucky, October 4
      9, 1992. Abstracts.

PMID- 1358159
TI  - International Symposium on Control of Human Pathogens in Poultry. Doorwerth, The
      Netherlands, May 17, 1991.

PMID- 1358158
TI  - Assessment of bronchial effects following topical administration of butylamino
      phenoxy-propanol-acetate, an oculoselective beta-adrenoceptor blocker in
      asthmatic subjects.
AB  - 1. Butylamino-phenoxy-propanol-acetate (BPPA) is a new topical oculoselective
      beta-adrenoceptor blocker for the reduction of intraocular pressure (IOP) in man.
      Its potency on the airways of normal subjects was identical with that of placebo.
      A study was carried out to determine the potential of BPPA to cause
      bronchoconstriction in mild asthmatics (FEV1 greater than or equal to 60%
      predicted) with normal IOP. 2. Twelve nonsmoking outpatients who
      bronchoconstricted to 0.25 or 0.50% of timolol eye drops (fall in FEV1 23.33 +/-
      1.20% (mean +/- s.e. mean), range 16-30) were investigated in this double-masked,
      randomized, 3-period, crossover study. On three different occasions six
      incremental concentrations of BPPA (range: 0.1-2%; maximum cumulative
      concentration 4%), timolol (0.1-1%; 2%), and placebo were administered
      bilaterally until bronchoconstriction (decrease in FEV1 greater than or equal to
      20% and in specific airway conductance (sGaw) greater than or equal to 35%
      simultaneously) or the maximum cumulative concentration was reached. 3. Airway
      response was measured as change in FEV1 and sGaw and dose-response curves to
      timolol, BPPA and placebo were performed. IOP was measured 3 h after the highest
      concentration of each study day. 4. Timolol caused dose-dependent falls in FEV1
      and sGaw as well as clinical symptoms of respiratory distress in all subjects.
      The median cumulative concentrations of timolol required to decrease FEV1 by 20%
      and sGaw by 35% were 0.98% and 1.53%. Neither placebo (P greater than 0.05) nor
      BPPA (P greater than 0.05) caused a significant change in sGaw. A fall in FEV1 by
      20% not accompanied by a simultaneous fall in sGaw by 35% was found in four
      subjects following BPPA and in five subjects following placebo.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1358160
TI  - Adhesion of Salmonella typhimurium var. copenhagen in the intestines of pigeons.
AB  - The attachment of Salmonella typhimurium var. copenhagen to the intestinal
      epithelium of pigeons was studied. After experimental infection, the intestines
      of both young and adult pigeons were examined in vivo and in vitro.
      Investigations were carried out by electron and immunofluorescence microscopy.
      Attachment of the Salmonella strain to duodenal epithelium was established.
      Following repeated washing after inoculation, bacterial cells could be seen by
      SEM and TEM in association with the surface structure of the tissue. The adhesive
      properties of fimbriae, which are also involved in haemagglutination, could be
      demonstrated.

PMID- 1358161
TI  - Restriction fragment length polymorphism analysis of Listeria monocytogenes and
      its application to epidemiological investigations.
AB  - The restriction fragment length polymorphisms (RFLPs) of 64 random and
      potentially related strains of Listeria monocytogenes were analysed and compared
      using a probe comprised of two L. monocytogenes chromosome fragments cloned into
      a lambda vector. Twelve RFLP types were defined using 14 isolates of clinical
      origin, 42 food isolates and eight food associated environmental strains. Of the
      RFLP types, some were common to a particular serovar and source, whereas others
      were widespread amongst all serovars and sources. One of the two most common RFLP
      patterns was associated with serovar 1/2 isolates from food or the environment,
      whereas another dominant pattern was associated most commonly with serovar four
      isolates from all sources. The potential relationships between epidemiologically
      related strains were examined, with the analysis of types from a suspected
      listeriosis outbreak, from clinical maternal-foetal cases, and from an ice-cream
      factory environmental study. Serotyping alone was not a sufficient marker for the
      comparison of these strains whereas further discrimination of strains was
      possible with RFLP analysis.

PMID- 1358162
TI  - Beta blockers and quality of life.
AB  - Hypertension is an asymptomatic conditions which can be life threatening. It is
      thus important that hypertensive patients maintain compliance with their therapy.
      This can be put at risk if the patient experiences adverse affects or if the
      patient's lifestyle is significantly altered in some way. The ability to perform
      daily activities and derive satisfaction is referred to as quality of life. With
      this in mind the published literature is reviewed here with regard to comparative
      studies involving beta-blockers. The balance of the evidence reviewed indicates
      that there are differences in quality of life between ACE inhibitors and the non
      selective, lipophilic beta blocker, propranolol, favouring the former. However,
      this is clearly not a class difference as atenolol, which is beta 1 selective and
      hydrophilic, results in a similar quality of life profile to that with either
      captopril or enalapril. This difference between atenolol and propranolol probably
      arises out of their differing pharmacology, as opposed to any fundamental
      difference in their blood pressure lowering ability. There are probably too few
      studies to compare beta blockers and either calcium antagonists or diuretics
      definitively with regard to quality of life. What little evidence there is
      suggests a difference between propranolol and verapamil, with the latter giving
      the better quality of life. However, no difference was observed between verapamil
      SR and atenolol. Although data are very limited it appears that atenolol impacts
      more favourably than thiazide diuretics.

PMID- 1358163
TI  - c-erbB-2 positive breast tumours behave more aggressively in the first years
      after diagnosis.
AB  - In a retrospective study the expression of the c-erbB-2 oncogene was determined
      immunohistochemically in 276 breast cancer samples from 253 patients with the
      antibody 21N. The follow-up period was between 7 and 12 years. This study showed
      a trend for an inverse relationship between c-erbB-2 positive tumours and
      estrogen receptors (ER). A correlation was assessed between c-erbB-2 positive
      tumours and histological grade, liver metastases as first site of metastases,
      disease free survival time (DFS) in the second and third year after diagnosis and
      overall survival time (OST) in the third and fourth year after diagnosis. A trend
      was seen between c-erbB-2 positive tumours and tumour size. No correlation was
      found between c-erbB-2 positive tumours and age at diagnosis. The method of
      operation and lymph node involvement. From this study we conclude that there is a
      significant difference in prognosis the first years after diagnosis, but this
      difference seems to vanish in a longer follow-up period of 12 years. This
      provides us with an explanation for the discrepancies in literature concerning c
      erbB-2 expression and prognosis in breast cancer. Some investigators did not show
      differences in prognosis between positive and negative cases after a long follow
      up period whereas investigations with a short term follow-up period up to 2-3
      years have indeed established a more aggressive behaviour of c-erbB-2
      overexpressionary tumours.

PMID- 1358164
TI  - Proliferating cell nuclear antigen (PCNA) as a prognostic factor in non-Hodgkin's
      lymphoma.
AB  - The prognostic value of immunoperoxidase staining for proliferating cell nuclear
      antigen (PCNA) was studied in a series of 140 non-Hodgkin's lymphomas with median
      follow-up of 9 years. Lymphomas where > 50% of cells showed positive staining for
      PCNA had inferior 5-year survival as compared with those with less than 50% of
      positive cells (57% vs 41%, P = 0.008). The presence of > 50% of positively
      staining cells for PCNA was strongly associated with a larger than the median
      size of the SPF (median, 8.3%), and high histological grade of malignancy (P <
      0.0001 for both). Lymphomas with both a large percentage (> 50%) of PCNA positive
      cells and a larger than the median SPF had inferior outcome as compared with
      lymphomas where either one or both of these factors were small. Although PCNA
      staining was not an independent prognostic factor in a multivariate analysis, it
      appears to be supplementary to the SPF even if determined from old paraffin
      embedded tissue material.

PMID- 1358165
TI  - The effect of therapeutic drugs used in inflammatory bowel disease on the
      incidence and growth of colonic cancer in the dimethylhydrazine rat model.
AB  - An increased incidence of colonic cancer is associated with chronic inflammatory
      bowel disease. Sulphasalazine, metronidazole and more recently, modified forms of
      5-aminosalicylic acid are used for maintenance therapy of inflammatory bowel
      disease. In a series of experiments, we used the 1,2-dimethylhydrazine animal
      model of colonic cancer in conjunction with these drugs, to study the effect on
      the development of colon cancer. Inbred male Wistar rats were divided into groups
      receiving orally: metronidazole 18 mg Kg-1 dy-1; sulphasalazine 60 mg Kg-1 dy-1;
      5-aminosalicylic acid 30 and 60 mg Kg-1 dy-1 and olsalazine 60 mg Kg-1 dy-1
      administered daily. Half of each group also received weekly injections of DMH 40
      mg Kg-1. Metronidazole, sulphasalazine and 30 mg Kg-1 dy-1 5-aminosalicylic acid
      were co-carcinogenic, increasing either the number of cancers or tumour size. In
      contrast 60 mg Kg-1 dy-1 5-aminosalicylic acid inhibited tumour size and
      olsalazine had no effect. These results may have a bearing on long term
      maintenance therapy in inflammatory bowel disease.

PMID- 1358166
TI  - A comparison of membrane properties and composition between cell lines selected
      and transfected for multi-drug resistance.
AB  - Cell lines selected (CHRC5) and transfected (LR-73-1A) for multi-drug resistance
      have total lipid compositions which are indistinguishable between resistant and
      parental cells. Lipid composition was evaluated by 1H NMR and the total fatty
      acid content by GLC. No change in surface hydrophobicity, as measured with the
      fluorescent probe dansyl-PE, was observed as a result of transfection of CHO
      cells with the mdr1 gene. However, the selected cell line, CHRC5, showed a
      decreased surface hydrophobicity. This decreased surface hydrophobicity was
      indicated by an 8 nm increase in the fluorescence emission of dansyl-PE in the
      CHRC5 cell line compared with the AB1. Both resistant cell lines showed an
      increase in the polarisation of the fluorescent probe, TMA-DPH in the plasma
      membranes corresponding to a 14% and a 24% change in fluorescence polarisation
      for the selected and transfected cell lines, respectively. This is indicative of
      reduced mobility of the acyl chains in the resistant cell lines. Both the CHRC5
      and the transfected cell lines showed almost a 2-fold increase in the initial
      rate of membrane cycling. The membrane cycling could be inhibited by a known
      bilayer stabiliser, the N-carbobenzoxy-D-Phe-L-Phe-Gly. These results indicate
      that the properties of the plasma membrane from resistant cells are altered
      compared with their parental cell line.

PMID- 1358167
TI  - Tumour-associated hypoglycaemia in a murine cachexia model.
AB  - Animals bearing a cachexia-inducing tumour, the MAC16 adenocarcinoma, showed a
      progressive decrease in blood glucose levels with increasing weight loss, while
      animals bearing a histologically similar tumour, the MAC13 adenocarcinoma, showed
      no change in either body weight or blood glucose levels with growth of the
      tumour. The effect of the MAC16 tumour on blood glucose levels appeared to be
      unrelated to food intake, glucose consumption by the tumour, or to the production
      of increased levels of IGF-I and IGF-II mRNA by the tumour cells. The
      relationship between the induction of cachexia and alteration in blood glucose
      levels remains unknown.

PMID- 1358169
TI  - Beta-thalassaemia minor and porphyria cutanea tarda.
AB  - A case of porphyria cutanea tarda occurring in association with beta-thalassaemia
      minor is reported in a 33-year-old Northern-Irish woman. Aetiological factors in
      this case included oral and parenteral iron therapy for refractory anaemia which
      was subsequently diagnosed as beta-thalassaemia minor, and the use of an
      oestrogen-containing oral contraceptive pill.

PMID- 1358168
TI  - High-dose tamoxifen as an enhancer of etoposide cytotoxicity. Clinical effects
      and in vitro assessment in p-glycoprotein expressing cell lines.
AB  - Twenty-six patients with relapsed or drug-resistant cancer were treated with a
      combination of oral etoposide (300 mg day-1 for 3 days) and high-dose oral
      tamoxifen as a potential modulator of drug resistance (480 or 720 mg day-1 for 6
      days beginning 3 days before etoposide). One patient with relapsed high-grade
      lymphoma and one with adenocarcinoma of unknown primary site has a partial
      response. Toxicity consisting of nausea, vomiting and subjective dizziness,
      unsteadiness of gait and malaise occurred during tamoxifen treatment. Serum
      levels of tamoxifen averaged 3-3.5 microM on day 4 of all courses of treatment at
      both 480 and 720 mg day-1. N-desmethyltamoxifen levels were lower than tamoxifen
      during the first course (2 microM) but increased to equal tamoxifen levels during
      the second course. Didesmethyltamoxifen levels remained below 1 microM. In vitro,
      both tamoxifen and the standard modulator of multidrug resistance, verapamil,
      produced minor enhancement of etoposide cytotoxicity in the MCF-7 wt cell line
      but produced no enhancement with any other cell line. High, intermittent doses of
      tamoxifen can be given with acceptable toxicity and produce serum levels that
      have been shown to modulate drug resistance in vitro. In vitro, however, such
      levels have no significant effect on etoposide cytotoxicity towards a range of
      wild-type and MDR cell lines.

PMID- 1358171
TI  - Detection of activity of P-glycoprotein in human tumour samples using rhodamine
      123.
AB  - Based on the fluorescent properties of the dye rhodamine 123 (Rh123), which is
      transported by the membrane efflux pump P-glycoprotein (P-gp), we developed a
      functional flow cytometric assay for the detection of multidrug-resistant (MDR)
      cells. Using drug sensitive cell lines (KB-3-1) and MDR mutants (KB-8-5, KB-C1)
      experimental conditions were established that enabled demonstration of
      significant differences in Rh123 efflux and accumulation. Subsequently we
      investigated the applicability of this functional assay for the prediction of MDR
      in human peripheral blood and bone marrow samples. Using two-colour flow
      cytometry, the leukaemic blast cells of six patients suffering from acute myeloid
      leukaemia (AML) were analysed. In three cases the blast cells showed a rapid and
      marked Rh123 efflux. In the presence of MDR inhibitors these cells retained
      Rh123. To determine whether the efflux of Rh123 was associated with P-gp
      expression, the leukaemic cells were stained with the monoclonal antibody MRK-16.
      In addition extracted RNA was analysed by polymerase chain reaction to evaluate
      the expression of mdr 1 mRNA. In all three Rh123+ cases mdr 1 mRNA was detectable
      whereas only one AML case expressed P-gp. In comparing Rh123 with daunorubicin,
      which also allows the detection of MDR cells, accumulation studies proved Rh123
      to be the more sensitive drug for flow cytometric MDR screening. Additionally,
      two-colour flow cytometry was much easier to perform with Rh123 than with
      daunorubicin. Our results indicate that flow cytometric measurement of Rh123
      accumulation/efflux proves applicable to detect MDR cells in heterogenous
      clinical samples.

PMID- 1358170
TI  - Inhibition of chick embryo lysyl oxidase by various lathyrogens and the
      antagonistic effect of pyridoxal.
AB  - Lysyl oxidase, which cross-links collagen and elastin, was obtained from chick
      embryo bone and cartilage and its substrate, elastin, from aorta. The enzyme was
      studied using an improved assay which enabled the stability of the substrate to
      be monitored. The enzyme was fully inhibited in vivo by beta-aminopropionitrile,
      semicarbazide, thiosemicarbazide and isoniazid and in vitro by beta
      aminopropionitrile and semicarbazide but only partially by thiosemicarbazide and
      isoniazid. Penicillamine, which solubilizes collagen by labilizing Schiff base
      cross-links in vivo and which prevents stable cross-link formation in vitro
      indirectly by binding to aldehyde groups on collagen, was shown to have no direct
      inhibitory effect on lysyl oxidase in vivo or in vitro. Homocysteine, which also
      solubilizes collagen by a mechanism similar to penicillamine does not inhibit
      lysyl oxidase either in vivo or in vitro. Pyridoxal reversed the inhibition of
      lysyl oxidase by semicarbazide and isoniazid in vivo but was unable to reverse
      that produced by either beta-aminopropionitrile or thiosemicarbazide. These
      results can be explained by the presence of a sulphydryl group near the active
      site of lysyl oxidase, which can form a complex with the nitrile group on beta
      aminopropionitrile or with the thiol group on thiosemicarbazide leading to
      irreversible inhibition.

PMID- 1358172
TI  - Expression of myeloid associated antigens in chronic lymphocytic leukaemia.

PMID- 1358173
TI  - Symposia abstracts from the 24th Congress of the International Society of
      Haematology. London, 23-27 August 1992.

PMID- 1358174
TI  - Activin A induced expression of a fork head related gene in posterior
      chordamesoderm (notochord) of Xenopus laevis embryos.
AB  - A gene family encoding the fork head/HNF-3 domain has been identified in the
      South African clawed frog, Xenopus laevis. Screening of genomic DNA and gastrula
      stage derived cDNA libraries with a DNA fragment encoding the Drosophila fork
      head domain led to the isolation of a number of different clones encoding this
      motif. While one of the Xenopus fork head sequences, XFD-3, represents the
      Xenopus counterpart to rat HNF-3 beta, all other sequences encode novel types of
      fork head related proteins. Here we report on XFD-1, a DNA binding protein which
      can bind to the HNF-3 alpha target sequence. Analysis of temporal and spatial
      expression revealed that the gene is activated at blastula stage and that
      transcripts are localized in a rather thin stripe of cells invaginating the
      dorsal blastopore lip (organizer) during gastrulation. XFD-1 mRNA is localized
      within the notochord and, by the end of neurulation, is no longer detectable. In
      the animal cap assay the gene is activated by incubation with the vegetalizing
      factor (activin A) but not with bFGF.

PMID- 1358175
TI  - Severe psychosis and the adrenal androgens.
AB  - Past literature suggests a link between certain psychotic states and adrenal
      androgen production, including Dehydroepiandrosterone (DHEA). A group of severely
      psychotic androgenized females, refractory to substantial amounts of
      neuroleptics, has been identified for whom endocrine testing revealed abnormally
      high levels of DHEA. A similar group has been identified among the severely
      psychotic male population. Improvement in psychosis appears to occur as DHEA
      returns to its normal range using standard low dose Dexamethasone suppression.

PMID- 1358176
TI  - Recollections of B. F. Skinner.

PMID- 1358177
TI  - Comparison of two molecular weight markers used in DNA-profiling.
AB  - DNA-profiling was performed on DNA from human blood samples. Restriction was
      performed with HinfI and the fragments were analysed with the single locus probes
      MS1, MS31, MS43a, and YNH24. Calculations of the sizes of DNA-fragments in the
      range from 1.4 to 22 kilobase pairs (kb) were performed with two different size
      markers: the Amersham marker SJ5000 and the Gibco BRL marker 4401SA. The standard
      deviation of the difference between duplicate determinations was significantly
      lower with the Gibco BRL marker than with the Amersham marker. Calculation of the
      fragment lengths with the two markers differed significantly, especially in the
      high molecular weight region (> 8 kb). Fragment lengths were 3-8% (kb) higher
      with the Amersham marker than with the Gibco BRL marker which corresponds to a
      difference of 1.0-1.8 mm in migration distance. The difference was enhanced in
      the presence of ethidium bromide. The consequences of the replacement of the
      Amersham marker by the Gibco BRL marker in practical casework is discussed.

PMID- 1358179
TI  - XVIIth Congress of the European Society for Medical Oncology. Lyon, France,
      November 7-10, 1992. Abstracts.

PMID- 1358178
TI  - pMCT 118 (D1S80): a new allelic ladder and an improved electrophoretic separation
      lead to the demonstration of 28 alleles.
AB  - Population data studies carried out on caucasians from Northwest Germany (n =
      218) using the AMPFLP system pMCT 118 (D1S80). The method used in a previous
      study (Rand et al. 1992) for pMCT 118 could be improved by increasing the
      electrophoretic separation length from 10 to 20 cm and by using an extended
      allelic ladder which allowed the distinction of 8 additional alleles (a total of
      28 alleles). Out of the 8 additional alleles 5 could be differentiated which
      differed within the 16 bp repeat sequence. The allele frequencies found were
      compared to population data from American caucasians, Hispanics and black
      Americans (Eisenberg and Maha 1991). All populations with the exception or black
      Americans, showed good agreement.

PMID- 1358181
TI  - Retinoids, retinoid-responsive genes, cell differentiation, and cancer.

PMID- 1358180
TI  - A ligand for the erbB-2 oncogene product (gp30) induces differentiation of human
      breast cancer cells.
AB  - The human erbB-2 oncogene encodes a tyrosine kinase receptor. A ligand for the
      erbB-2 receptor (gp30), with an apparent molecular weight of 30,000, was reported
      to modulate the growth of cells overexpressing erbB-2. Whereas low concentrations
      of gp30 induced proliferation of these cells, higher concentrations inhibited
      their growth. To elucidate the cellular mechanisms underlying cell growth
      inhibition by gp30, we tested the effect of this ligand on cell growth and
      differentiation of the human breast cancer cells AU-565 and MDA-MB-453 (which
      overexpress erbB-2) and MCF-7 cells (which express low levels of this
      protooncogene). Ligand concentrations that inhibited growth in cells
      overexpressing erbB-2 induced apparent differentiation of cells with a more
      mature phenotype, i.e., with characteristics such as inhibited cell growth,
      altered cytoplasmic and nuclear morphology, and increased synthesis of milk
      components (casein and lipids). No significant effect of the ligand was observed
      in the human breast cancer cell line MCF-7. Concomitant with the induction of
      differentiation in AU-565 and MDA-MB-453 cells, the erbB-2 protein was
      translocated from membrane to the cytoplasm and perinuclear sites. These findings
      indicate that ligand-induced growth inhibition in cells overexpressing erbB-2 is
      associated with an apparent induction of differentiation.

PMID- 1358182
TI  - Negative symptoms and EEG alpha activity in schizophrenic patients.
AB  - Quantitative analyses of electroencephalographic (EEG) recordings in
      schizophrenic patients have often demonstrated reduced alpha band (8-13 Hz)
      activity. However, this finding is not universal and there is some evidence that
      subgroups of schizophrenics may differ in overall or lateralized levels of EEG
      alpha activity. To investigate this issue, the authors examined relationships
      between clinical ratings performed at the time of EEG recording and resting alpha
      power and coherence in 14 medication free schizophrenic patients. Nine channels
      of previously recorded resting (eyes open) EEG were transformed to average
      reference prior to spectral analysis and transformed to source derivation prior
      to calculation of inter-electrode coherences. Patients were rated with the Brief
      Psychiatric Rating Scale (BPRS), from which subscales corresponding to negative
      symptoms, positive symptoms, paranoia, and anxiety/depression were derived.
      Ratings and EEG measures were also obtained on 10 of the schizophrenic patients
      after neuroleptic treatment. Multiple regression with repeated measures was used
      to examine the influence of the subscale scores on bilateral log alpha power and
      both within- and between-hemisphere alpha coherence at selected locations. Prior
      to treatment, negative symptoms varied inversely with alpha power (p < 0.02),
      within-hemisphere alpha coherence (p < 0.03), and between-hemisphere coherence (p
      = 0.053). The effect of negative symptoms on alpha power was bilateral, but the
      effect on within-hemisphere coherence tended (p = 0.053) to be right-sided. After
      treatment these relationships were no longer present. The possible implications
      of and the effects of drug treatment on an association between negative symptoms
      and reduced alpha activity are discussed.

PMID- 1358183
TI  - EEG-brain mapping. A method to optimize therapy in schizophrenics using absolute
      power and center frequency values.
AB  - In this study EEG-spectral parameters like mean alpha-power values and center
      frequency values are computed as maps and compared using significant probability
      mapping. The parameters are used to describe changes of the functional state of
      the brain after neuroleptic depot injection (Haldol-Decanoate) in schizophrenic
      patients. The absolute alpha-power increased significantly (p < 0.01), especially
      within the first week after injection mostly in the left hemispheric regions. The
      center frequency decreased most significantly (p < 0.02) between the first and
      second week after haldol depot injection at the right occipital regions. Both
      parameters are efficient to describe functional changes correlated with clinical
      symptomatology, even 3-5 days earlier. Thus, EEG power and center frequency
      mapping can be used very efficiently to estimate the optimal time between
      sequential neuroleptic depot injections.

PMID- 1358184
TI  - Abnormal premovement brain potentials in schizophrenia.
AB  - We assessed scalp-recorded movement related potentials (MRPs) generated prior to
      voluntary movements in chronic, medicated schizophrenics (n = 9) and age matched
      normal controls (n = 9). MRPs were recorded in a self-paced button press task in
      which subjects pressed a button with either their right, left or both thumbs
      (experimental condition I, II and III respectively). Controls generated a slowly
      rising readiness potential (RP) at about 1000 ms, a negative shift (NS') at about
      450 ms and a motor potential (MP) at about 100 ms prior to movement. The initial
      MRP components (RP and NS') were reduced in schizophrenics indicating an
      impairment of the voluntary preparatory process in schizophrenia. Results of the
      present study indicate a similarity of MRP findings in schizophrenics and
      reported MRPs (Singh and Knight, 1990) in patients with unilateral lesions of the
      dorsolateral prefrontal cortex. These findings provide further support for
      frontal lobe dysfunction in schizophrenia.

PMID- 1358185
TI  - Schizophrenia and porphobilinogen deaminase gene polymorphisms: an association
      study.
AB  - A genetic case-control study was conducted in a group of patients with
      schizophrenia (n = 67; DSM-III) and psychiatrically normal controls matched for
      ethnicity (n = 84), living in the same geographical area. Using three different
      DNA polymorphisms of the gene encoding porphobilinogen deaminase (PBGD), a
      candidate gene for schizophrenia, an association with schizophrenia could not be
      detected. No significant associations were detected even after sub-division of
      the cohort by ethnicity and by gender.

PMID- 1358186
TI  - Gender differences in cognition in schizophrenia.
AB  - Gender differences in cognition were investigated in schizophrenic inpatients and
      outpatients using the Dementia Rating Scale. Females displayed greater impairment
      on Attention and Conceptualization than males. Gender interacted with patient
      group for construction: females performed worse than males among inpatients and
      better among outpatients. Results may be related to the atypically early age of
      onset of females relative to males; attention to sampling and selection biases is
      needed in evaluating gender differences in cognition in schizophrenia.

PMID- 1358187
TI  - Clonal unresponsiveness results from an interaction between staphylococcal
      enterotoxin B and T cells expressing unexpected V beta elements.
AB  - The ability of staphylococcal toxins to stimulate large numbers of T cells has
      led to their designation as a superantigen. Previous studies have indicated that
      activation of T cells bearing particular V beta elements may be responsible for
      the toxic effects of these bacterial products. However, the widespread expression
      of functionally similar proteins by unrelated bacterial species suggests the
      possibility that these products may represent a successful microbial strategy for
      subversion of the host antibacterial response. We have examined the effects of
      the staphylococcal enterotoxin B (SEB) on T cell clones that express different V
      beta elements. We note that SEB stimulates clones bearing previously defined V
      beta elements to proliferate and to produce cytokines. In addition, we
      demonstrate that an interaction between SEB and the TCR of clones that express
      additional V beta elements, including V beta 2 and V beta 6, results in a sterile
      form of immunological activation. This activation phenotype is characterized by
      proliferation without detectable cytokine production and is followed by profound
      immunological unresponsiveness in vitro and in vivo. We propose that reduced
      levels of antibacterial responses resulting from this form of T cell
      unresponsiveness may account for the highly conserved expression of superantigens
      by diverse bacterial species.

PMID- 1358188
TI  - Glycosylphosphatidyl inositol-linked membrane protein expression by intestinal
      intraepithelial lymphocytes.
AB  - Murine intestinal intraepithelial lymphocytes (ilEL) represent a heterogeneous
      population of cells which contains both TCR alpha beta+ and TCR gamma delta+
      cells. In contrast to the TCR alpha beta+ cell population in peripheral lymphoid
      organs, the TCR alpha beta+ ilEL contain high numbers of Thy-1- cells. This
      negativity of ilEL for Thy-1, a glycosylphosphatidyl inositol (GPI)-linked
      membrane protein, is not the result of conformational changes of the Thy-1
      molecule. The absence of Thy-1 on TCR gamma delta+ and a subset of TCR alpha
      beta+ ilEL is furthermore not caused by a general defect in the processing of GPI
      linked proteins, since Thy-1- ilEL mainly express another GPI-linked protein, Qa
      2. However, TCR alpha beta+ and TCR gamma delta+ ilEL are also virtually negative
      for two other members of this family of activation-associated GPI-linked
      proteins, Ly-6A and Ly-6C. This unusual pattern of GPI-linked protein expression
      on TCR+ ilEL may be related to differences in cellular activation and signal
      transduction pathways between TCR+ ilEL and regular peripheral T cells.

PMID- 1358189
TI  - Do antigenic drift residues in influenza hemagglutinins of the H3 subtype qualify
      as contact sites for MHC class II interaction?
AB  - We have previously reported that a majority of hemagglutinin-specific and class
      II (Ak or Ad)-restricted T cell clones, elicited by natural infection with X31
      virus (H3N2 subtype), focus on regions of the HA1 subunit that have featured in
      antigenic drift and exhibit extensive diversity in their ability to discriminate
      between variant viruses with amino acid substitutions in these sites. The
      structural basis for the loss of recognition of a major antigenic site, HA1 120
      139, was investigated by (i) comparing the effects of amino acid substitutions in
      mutant hemagglutinins (HA1 129 Gly----Glu; 132 Gln----Glu; 135 Gly----Arg) with
      the corresponding substitutions in synthetic peptides or (ii) by assessing the
      effects of single amino acid substitutions (to Ala) in the alpha k chain
      (residues 50-79) on the ability of Ak transfectants to present peptides. Despite
      the failure to recognise mutant viruses, mutant peptides were recognised as
      efficiently as wild-type peptides in association with wild-type Ak. However, the
      mutant Ak transfectants identified a different set of alpha k residues (positions
      56, 65, and 72) as being critical for presentation of mutant peptides. Taken
      together with our previous findings that defects in antigen presentation of
      mutant hemagglutinin are reversed by single substitutions in the alpha k chain
      (residues 56 and 62), it would seem that the antigenic drift residues in mutant
      hemagglutinins alter the profile of contact sites with class II.

PMID- 1358190
TI  - Structural analysis of human anti-mouse H-2E xenorecognition: T cell receptor
      bias and impaired CD4 interaction contribute to weak xenoresponses.
AB  - T lymphocyte responses to the MHC of an evolutionarily distant species are known
      to be weak compared with responses against allogeneic MHC products within a
      species. This fact was used to examine the regions of human MHC class II
      molecules required for the stimulation of strong primary immune responses against
      MHC alloantigens. A panel of mouse DAP.3 transfectants expressing the products of
      wild-type and recombinant DR1/H-2Ek MHC class II genes paired to either DR alpha
      or H-2E alpha genes was generated, and tested as stimulator cells for purified
      human T cells. A strong proliferative response to DAP.3 transfectants expressing
      allogeneic HLA-DR molecules was seen. In contrast, weak or absent responses were
      recorded against DAP.3 cells expressing H-2E molecules. Substitution of the DR1
      beta chain with H-2E beta k led to a dramatic loss of recognition; alpha chain
      substitution had a less marked effect. Furthermore, replacement of the beta 2
      domain of DR1 with H-2E sequence caused 90% inhibition, whereas introduction of
      the beta 2 domain of DR1 into H-2Ek led to a 10-fold increase in T cell response.
      These results are most readily explained if the beta 2 domain contributes to the
      interaction site for the CD4 molecule. Substitution of either half of the beta 1
      domain led to a marked loss of response. This was more impressive following
      substitution of the TCR-contacting alpha-helical region of the domain.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1358191
TI  - Most residues on the floor of the antigen binding site of the class I MHC
      molecule H-2Kd influence peptide presentation.
AB  - A panel of 15 single alanine substitutions on the floor of the peptide binding
      groove of the murine class I histocompatibility molecule H-2Kd has been analyzed.
      All but two mutant molecules were expressed on the cell surface, and were tested
      for peptide binding and presentation to specific cytotoxic T lymphocytes. Eleven
      out of 13 mutant molecules appeared to be functionally altered. Five of the
      substituted residues were involved in the presentation of all peptides tested.
      Three participated in the presentation of certain peptides but not others. Three
      other residues participated in epitope formation through indirect interactions.
      Only two mutations had no detectable effect.

PMID- 1358192
TI  - Monoclonal antibodies in corneal transplantation.

PMID- 1358193
TI  - Photodamage of the conjunctiva in patients with porphyria cutanea tarda.
AB  - Ninety two patients with porphyria cutanea tarda (PCT) were examined
      ophthalmically in a paired case control study. The incidence of pinguecula and of
      pterygium was 8 and 2 times higher respectively, in PCT patients than in the
      control group. The photodamage to the conjunctiva is considered to be a result of
      the photoactivity of uroporphyrin in the tissues.

PMID- 1358195
TI  - Characterization of bovine MHC class II polymorphism using three typing methods:
      serology, RFLP and IEF.
AB  - Various methods, with different strengths and weaknesses, are currently used to
      define polymorphism of the bovine major histocompatibility complex (MHC) class II
      genes. A more complete characterization of bovine lymphocyte antigen (BoLA)
      haplotypes can be achieved by combining several of these methods. In this study
      BoLA class II polymorphism was characterized using three typing methods:
      serology, restriction fragment length polymorphism (RFLP), and isoelectric
      focusing (IEF). Twenty six Holstein-Friesian and 15 Angus cattle that carried an
      array of serologically defined BoLA haplotypes were selected for the study. The
      panel included 12 BoLA complex homozygotes. The three class II typing methods
      recognized polymorphism associated with the same or very tightly linked genes in
      the DQ-DR class II subregion. In total 25 BoLA-A locus (class I)--DQ-DR subregion
      (class II) haplotypes were defined. Three of the serological class II
      specificities, Dx1, Dx3, and Dx4, were associated with more than one RFLP defined
      DQ-DR haplotype. The other 4 class II specificities behaved as private
      specificities. One BoLA haplotype was found in both Holstein and Angus cattle.
      Two other BoLA haplotypes defined here have previously been described in other
      breeds. This suggests that these haplotypes exist in strong linkage
      disequilibrium.

PMID- 1358194
TI  - Prolongation of rat corneal graft survival by treatment with anti-CD4 monoclonal
      antibody.
AB  - A rat model of orthotopic corneal graft rejection was used to investigate the
      effect of depletion of subpopulations of immune cells by treatment with
      monoclonal antibodies. Though CD4+ cells were not eliminated completely by anti
      CD4 monoclonal antibodies there was a profound delay in the rejection times of
      orthotopic corneal allografts. Furthermore a third of the CD4+ depleted animals
      failed to reject corneal allografts by 100 days post grafting. Despite an almost
      complete depletion of circulating CD8+ cells, the anti-CD8 antibody treated
      animals rejected corneal allografts in a similar time course to allografted
      controls treated with a non-reactive control antibody OX21. These results
      demonstrate that CD8+ T-cells are not required for rejection of corneal
      allografts whereas CD4+ T-cells play a critical role in the rejection response.
      Treatment with anti-CD4 antibodies may have a useful clinical application.

PMID- 1358196
TI  - Monomorphic organization of human diversity (DH) heavy chain variable genes.
AB  - While recent evidence indicates that human immunoglobulin heavy chain variable
      (VH) genes exhibit a high degree of heterogeneity, little is known concerning the
      polymorphism of the diversity (DH) gene complex. This locus comprises two
      clusters, major and minor, which are physically linked with the VH locus. In
      assessing the variability of the human major and minor DH clusters, we found no
      evidence for a substantial restriction site polymorphism. We also noted that, in
      contrast to what was found in the Japanese population, the DH1 gene is not
      deleted in an appreciable proportion of the European population. We propose that,
      because DH genes impart the critical functions associated with the third
      complementarity-determining region, the genomic organization of the human DH
      locus has been evolutionarily conserved through selection pressure mechanisms.

PMID- 1358197
TI  - Human natriuretic peptide receptor-A guanylyl cyclase is self-associated prior to
      hormone binding.
AB  - The human natriuretic peptide receptor-A (NPR-A) guanylyl cyclase is specifically
      activated to synthesize cGMP by binding of atrial natriuretic peptide (ANP) to
      the receptor's extracellular domain. In this report, NPR-A monoclonal and
      polyclonal antibodies were used to assess the aggregation status of wild-type NPR
      A and a truncation mutant lacking most of the NPR-A cytoplasmic domain. On intact
      human embryonic kidney 293 cells, in the absence of ANP, recombinant human NPR-A
      is self-aggregated through disulfide bonds in an M(r) > 500,000, possibly
      tetrameric, complex. Under nonreducing conditions, truncated NPR-A was a monomer,
      indicating that the cytoplasmic domain is necessary for NPR-A self-association.
      In the presence of the homobifunctional cross-linker dithiobis(succinimidyl
      propionate), or disuccimidyl suberate, truncated NPR-A could be cross-linked as a
      dimer and trimer only in the presence of ANP. Wild-type NPR-A was cross-linked
      with disuccinimidyl suberate to an M(r) > 500,000 species in the absence of ANP,
      and with ANP, a smaller, M(r) approximately 400,000 receptor trimer cross-linking
      product was observed, together with the larger, possibly tetrameric complex. When
      whole cell stimulation of cGMP production by ANP was tested on the low level of
      endogenous 293 cell NPR-A, maximal stimulation was observed regardless of
      truncated NPR-A overexpression. The absence of a dominant negative effect by the
      truncated NPR-A, together with the cross-linking data, demonstrates that
      preassociated NPR-A is the functionally relevant form of this receptor.

PMID- 1358198
TI  - Effects of lithium on basal and modulated activities of the particulate and
      soluble guanylate cyclases in retinal rod outer segments.
AB  - A large amount of information regarding the kinetics of biochemical reactions
      involved in visual transduction was derived from electrophysiological studies on
      dark-adapted rod outer segments. Hodgkin et al. [(1985) J. Physiol. 358, 447-468]
      observed that when Na was replaced with Li in the perfusion solution bathing the
      rod outer segment, the dark current slowly declined to zero. This decline was
      thought to result from a rise in intracellular calcium which was hypothesized to
      inhibit guanylate cyclase activity and reduce the cyclic GMP concentration. Rod
      outer segments contain membrane and soluble guanylate cyclase activities, and we
      show here that Li directly inhibits both types of activities very strongly. Both
      the basal (at high calcium) and the stimulated (at low calcium) activities of the
      membrane enzyme were inhibited by Li. Half-maximal inhibition of the stimulated
      enzyme was at 30 mM Li while for the basal activity it was at 100 mM. Over 80% of
      the activated enzyme was inhibited at 110 mM Li. The soluble guanylate cyclase
      activity was stimulated by nitroprusside. One hundred millimolar Li inhibited the
      basal activity by 20-30%, but the inhibition of the nitroprusside-stimulated
      (soluble) enzyme was much stronger, resembling that of the activated membrane
      enzyme. Half-maximal inhibition occurred at 30 mM, and about 80% inhibition was
      found at 100 mM Li. Stimulation of the soluble enzyme by nitroprusside was
      independent of calcium in the physiological range. The inhibition of the
      stimulated enzyme by Li was similarly independent of calcium, except at
      unphysiologically high concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358199
TI  - Energy-dependent conversion of transformed cytosolic glucocorticoid receptors
      from soluble to particulate-bound form.
AB  - We have recently published that soluble cytosolic glucocorticoid receptors are
      converted to a particulate form when they are incubated at 37 degrees C in a
      tubulin-polymerizing buffer [Pratt, W. B., Sanchez, E. R., Bresnick, E. H.,
      Meshinchi, S., Scherrer, L. C., Dalman, F. C., & Welsh, M. J. (1989) Cancer Res.
      (Suppl.) 49, 2222s-2229s]. In this work, we further define this phenomenon and
      demonstrate that the L-cell glucocorticoid receptors are binding to a protein
      particulate composed largely of cytoskeletal proteins. Incubation of L-cell
      cytosol with glutamate at 37 degrees C converts the glucorticoid receptor to a
      form that pellets when cytosol is centrifuged at 150000g. The particulate
      material formed in a temperature-dependent and glutamate-dependent manner
      contains a large amount of tubulin, actin, and vimentin, but it is not the
      product of a cold-labile, colchicine-sensitive polymerization process. Very few
      cytosolic proteins are present in this complex, but the glucocorticoid receptor
      is tightly bound to it. Binding of the receptor to the cytoskeletal complex
      occurs after receptor transformation and is at least partially energy-dependent.
      Examination of the behavior of beta-galactosidase receptor fusion proteins and
      the nti glucocorticoid receptor demonstrates that residues 445 to the COOH
      terminus of the receptor (DNA-binding and hormone-binding domains) contain the
      features required for binding to the cytoskeletal complex. Although it is the
      transformed receptor that associates tightly with the complex, DNA-binding
      activity is not required for association with the cytoskeletal
      particulate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358200
TI  - Carrier-mediated glutamate secretion by Corynebacterium glutamicum under biotin
      limitation.
AB  - Previous studies have demonstrated the involvement of a carrier system in
      glutamate secretion by Corynebacterium glutamicum under biotin limitation
      (Hoischen, C. and Kramer, R. (1989) Arch. Microbiol. 151, 342-347). In a detailed
      analysis of the export process we found secretion to be independent of secondary
      forces: (i) glutamate was secreted at high rate even when external glutamate
      exceeded the internal concentration, (ii) movement of neither protons nor
      potassium or chloride ions was found to be coupled to glutamate secretion, and
      (iii) secretion continued unaffected after breakdown of the membrane potential.
      Instead, under conditions leading to variation of glutamate secretion activity, a
      correlation of secretion rate and the intracellular ATP-pool was observed. Thus,
      ATP or a related high-energy metabolite is thought to be involved in the activity
      of the glutamate secretion system.

PMID- 1358201
TI  - Characterization of three arylsulfatases in semen: seminolipid sulfohydrolase
      activity is present in seminal plasma.
AB  - Sperm cells and seminal plasma of various mammals contain high levels of
      arylsulfatase. In the present study, we investigated the composition of soluble
      AS in these compartments of boar semen by analysing sperm cells and seminal
      plasma using anion-exchange chromatography. Seminal plasma contained both
      arylsulfatase B (2.4 units per ml), an enzyme which desulfates
      sulfoglycosaminoglycans and probably sulfoglycoproteins, and arylsulfatase A
      (10.2 units per ml), an enzyme which desulfates sulfogalactolipids. Sperm cells
      contained only arylsulfatase A, which differed biochemically from the
      extracellular arylsulfatase A of seminal plasma (2.6 units per ml). Both types of
      arylsulfatase A desulfate seminolipid, the natural sulfolipid substrate in sperm,
      as well as two brain sulfatides. The possible physiological consequences of the
      presence of extracellular arylsulfatases in seminal plasma for spermatozoa are
      discussed.

PMID- 1358202
TI  - Nucleotide sequence and expression in Escherichia coli of the cephalosporin
      acylase gene of a Pseudomonas strain.
AB  - The gene encoding cephalosporin acylase, which hydrolyzes 7-beta-(4
      carboxybutanamido)-cephalosporanic acid (GL-7ACA) to 7-aminocephalosporanic acid
      (7ACA) and glutaric acid, was cloned from a Pseudomonas sp. strain V22 and
      expressed in Escherichia coli, in a two-cistron system, and the enzyme was
      purified and characterized. The purified enzyme was composed of two non-identical
      subunits, their molecular weights were estimated by SDS-PAGE to be 40,000 and
      22,000, and had a pI of 4.6. The amino acid sequence of the enzyme, deduced from
      the nucleotide sequence, showed high similarity (97%) with that of a previously
      reported acyI-encoded cephalosporin acylase. Cephalosporin acylase also resembles
      the bacterial gamma-glutamyl transpeptidases (GGTs) with respect to their
      molecular organization and amino acid sequence, but differs from them with
      respect to catalytic and immunological properties. Purified enzyme exhibited not
      only cephalosporin acylase activity, but also GGT activity. The Km values of the
      enzyme for GL-7ACA and L-gamma-glutamyl-p-nitroanilide were 6.1 and 3.8 mM,
      respectively. Cephalosporin acylase was not recognized by antibodies prepared
      against bacterial GGTs.

PMID- 1358203
TI  - Amplification and direct sequencing of a cDNA encoding human cytosolic 3-hydroxy
      3-methylglutaryl-coenzyme A synthase.
AB  - Cytosolic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase (E.C. 4.1.3.5) is a
      highly regulated enzyme involved in isoprenoid biosynthesis and therefore a
      potential target for cholesterol-lowering drugs. Up to now, primary structure
      data have only been available for chicken, rat and hamster HMG-CoA synthase.
      Using in vitro amplification and direct sequencing, we have determined the
      nucleotide sequence of the coding region of the human cytosolic 3-hydroxy-3
      methylglutaryl CoA synthase cDNA.

PMID- 1358204
TI  - Cloning and sequencing of the human homeobox gene HOX4A.
AB  - The HOX4A gene, one of the homeobox-containing genes on human chromosome 2, has
      been isolated by screening a genomic cosmid library with a HOX4B cDNA probe. The
      HOX4A gene consists of at least two exons separated by a long intron of 1860 bp.
      According to conceptual translation, the HOX4A protein is predicted to be
      composed of 416 amino acid residues. Interestingly, the HOX4A protein has a
      sequence, Pro-Ala-Ser-Gln-Ser-Pro-Glu-Arg-Ser, eight amino acids downstream from
      the homeodomain, which is similar to that containing a phosphorylation site in
      pp60c-src, Pro-Ala-Ser-Gln-Thr-Pro-Asn-Lys-Thr. However, the HOX2G protein, which
      exhibits a paralogous relationship with the HOX4A protein, does not possess the
      sequence which is similar to that in pp60c-src. A comparison of the predicted
      HOX4A protein with the HOX2G protein revealed four regions of amino acid sequence
      similarities: an N-terminal tetrapeptide, a pentapeptide (pre-box) upstream of
      the homeodomain, the homeodomain and a C-terminal octapeptide.

PMID- 1358205
TI  - 2nd European Symposium on Calcium-Binding Proteins in Normal and Transformed
      Cells. Marseilles, France, 1-6 March 1992.

PMID- 1358206
TI  - Recoverin, a novel calcium-binding protein from vertebrate photoreceptors.
AB  - Photoreceptor guanylyl cyclase activity is modulated by an endogenous calcium
      binding protein called recoverin. A modified isolation procedure for recoverin
      using gel-filtration chromatography instead of a heat denaturation step is
      presented. The elution volume of recoverin corresponds to a monomer. Recoverin
      exhibits a calcium-dependent mobility shift in a native gel electrophoresis.
      Isoelectric focusing revealed a pI of 5.25. No subspecies of recoverin were
      detected.

PMID- 1358207
TI  - Arachidonic acid regulates unsaturated fatty acid synthesis in lymphocytes by
      inhibiting stearoyl-CoA desaturase gene expression.
AB  - This work was based upon the observation that a reduction in the level of serum,
      provided to murine lymphocytes in culture, augmented endogenous unsaturated fatty
      acid (UFA) synthesis. Since the phospholipids of BW5147 cells grown in 1% serum
      were especially deficient in arachidonic acid (20:4), and given the findings of
      previous workers, we suspected that the availability of exogenous 20:4 in serum
      might correlate with the squelching of UFA synthesis. Indeed, after a 5 h
      exposure to 4-28 microM 20:4, the 20:4 content of BW5147 cell phospholipids
      increased from 1% to 15% of the total fatty acids with a coincident reduction in
      18:1 synthesis to approx. 30% of starting values. Subsequent studies were done to
      define the mechanism by which 20:4 down-regulates 18:1 synthesis. The results
      indicated that 20:4 inhibited endogenous 18:1 synthesis by reducing stearoyl-CoA
      desaturase (SCD) enzyme activity. Moreover, as determined by Northern blot
      analyses, the inhibitory effect of 20:4 on stearoyl-CoA desaturase activity
      coincided with decreased stearoyl-CoA desaturase mRNA levels. Exposure of BW5147
      cells to either 20:4, actinomycin D, or both, resulted in a temporal decay of
      stearoyl-CoA desaturase mRNAs with half-lives ranging from 4.0 h to 4.4 h. Such a
      similarity in decay times implied that 20:4 regulates stearoyl-CoA desaturase
      expression by inhibiting transcription. This was confirmed by nuclear run-on
      studies in which 20:4 was found to inhibit transcription of nascent stearoyl-CoA
      desaturase mRNA. Collectively, these findings implicate 20:4 as an important
      regulator of stearoyl-CoA desaturase gene expression, and hence UFA synthesis, in
      lymphoid cells.

PMID- 1358209
TI  - Utility of the parent-neutral loss scan screening technique: partial
      characterization of urinary metabolites of U-78875 in monkey urine.
AB  - Metabolites of an antianxiety-sedative drug candidate (U-78875; 3-(5-cyclopropyl
      1,2,4-oxadiazol-3-yl)-5-(1-methylethyl)-imidazo[1 ,5-alpha] quinoxalin-4(5H)-one
      (I)) present in the urine of monkeys were detected using tandem mass spectrometry
      (MS/MS) by application of parent ion scans and characterized or partially
      characterized by performing daughter ion scans of the pseudo-molecular ions of
      suspected metabolites. The use of liquid secondary ion mass spectrometry
      ionization of crude urinary extracts in combination with tandem quadrupole MS/MS
      analyses using parent ion scans of m/z 69 and subsequent daughter ion scans
      characterized unmetabolized I and N-dealkyl I (U-85466) and partially
      characterized aryl hydroxyl, aryl hydroxyl-N-dealkyl, aryl O-glucuronide, aryl O
      glucuronide-N-dealkyl, aryl O-sulfate and aryl O-sulfate-N-dealkyl metabolites.
      From these data it was concluded that some of the metabolic pathways involved in
      the biotransformation of U-78875 include N-dealkylation, aryl hydroxylation and
      conjugation of aryl hydroxides. Several other metabolites of U-78875 not detected
      using this analytical approach were subsequently identified by alternative mass
      spectrometric approaches. These data clearly demonstrated both the utility and,
      just as important, the limitations of the parent-neutral loss scan screening
      technique in detecting drug metabolites in complex biological milieux.

PMID- 1358208
TI  - P-glycoprotein genes in the winter flounder, Pleuronectes americanus: isolation
      of two types of genomic clones carrying 3' terminal exons.
AB  - In mammals, P-glycoprotein (P-gp) is encoded by two or more highly conserved
      genes that differ in their abilities to transport drugs. One isoform class (class
      I) is consistently associated with the multidrug resistance phenotype, while the
      other (class III) is not. This study was designed to enumerate the P-gp genes in
      fish and determine how they are related to the two functional classes already
      defined in mammals. Southern blot analysis using a conserved single exon from the
      3' terminal region of hamster P-gp cDNA (pEX1-172) as a probe indicated that
      there were two P-gp genes in right-eye flounders. Subsequently, two sets of
      clones were isolated from a winter flounder genomic library that correspond to
      the 3' ends of the two flounder P-gp genes. Sequence analysis was done on two key
      areas: the 3' ATP binding site and the 3' terminal exon, both of which were found
      to be homologous with their mammalian counterparts. Despite high levels of
      sequence identity in the predicted coding regions of the gene fragments it has
      not been possible to use these sequences to relate the homologs to particular
      mammalian classes of P-gp genes, perhaps because of gene conversion between
      mammalian P-gp genes. These cloned sequences are the first set of P-gp genes
      reported in lower vertebrates and will be useful for delineating the expression
      of P-gp genes in fish and understanding the role of P-gp in fish physiology.

PMID- 1358210
TI  - The chiral chromatographic separation of beta-adrenoceptor blocking drugs.
AB  - Over 100 chromatographic procedures for the separation of beta-blocker
      enantiomers are reviewed including a large number for the analysis of biological
      samples. All the principal chiral chromatographic procedures have found use,
      namely Chiral Mobile Phase Additives (CMPA), Chiral Derivatization Agents (CDA)
      and Chiral Stationary Phases (CSP). Chiral Mobile Phase Additives are less
      frequently employed than the other two procedures and many of the earlier methods
      were based on the use of CDAs. However, the recent development of sophisticated
      custom-made CSPs has allowed the separation of native (underivatized) analytes
      and this approach appears to be gaining in popularity. The beta-blockers are an
      extensive group of drugs and stereoselective separations have been reported for
      40 different structures.

PMID- 1358211
TI  - Aortocaval fistulas associated with ruptured abdominal aortic aneurysms.

PMID- 1358212
TI  - Oestrogen, progesterone, and glucocorticoid receptors in normal and neoplastic
      parathyroid glands.
AB  - OBJECTIVE: To verify the presence or absence of steroid receptors in the
      parathyroid glands of patients undergoing operations on the parathyroid and
      thyroid glands. DESIGN: Open experimental study. SETTING: Karolinska Hospital,
      Stockholm, Sweden. MATERIAL: 165 parathyroid glands from 137 patients, 108 of
      whom underwent operations on the parathyroid glands and 29 on the thyroid gland.
      INTERVENTIONS: Normal and neoplastic parathyroid tissue was analysed for its
      content of oestrogen and progesterone and glucocorticoid receptors using either
      ligand binding or antibodies raised against oestrogen and progesterone receptors.
      RESULTS: Positive reactions to female sex steroid receptors (defined as > 0.05
      fmol/microgram DNA) were uncommon (9%) regardless of the morphological
      classification of the glands or the age, sex, and menopausal status of the
      patients. Glucocorticoid receptors were detected in 107/163 (66%) of all glands
      analysed (mean value 0.43 fmol/micrograms DNA, range 0-44). Seventy of the 96
      diseased glands (73%) contained receptors, as did 27/67 normal glands from
      patients with primary hyperparathyroidism or those undergoing thyroid operations.
      The difference was again not associated with age, sex, and menopausal status.
      CONCLUSIONS: It seems unlikely that sex steroid hormones play a physiological
      part in the secretion of parathyroid hormone, but our finding of glucocorticoid
      receptors in normal as well as diseased parathyroid tissue suggests that they may
      have a role in the regulation of parathyroid function.

PMID- 1358213
TI  - Biochemical variables associated with bone density in patients with primary
      hyperparathyroidism.
AB  - OBJECTIVE: To clarify the association between primary hyperparathyroidism and
      cortical osteopenia. DESIGN: Open study. SETTING: Department of Surgery,
      University of Lund, Sweden. SUBJECTS: 38 patients with primary
      hyperparathyroidism. OUTCOME MEASURES: Correlation between bone density (measured
      by single photon absorption) and age; sex; serum concentrations of parathyroid
      hormone and ionised calcium; serum alkaline phosphatase activity; and serum
      concentration of calcium, phosphate, creatinine, urea, osteocalcin, 25
      hydroxycholecalciferol, and 1,25 dihydroxycholecalciferol. RESULTS: There was no
      difference in bone density between men and women. There was no correlation
      between bone density and severity of hypercalcaemia or age. No biochemical
      abnormality was peculiar to the seven patients whose bone density was more than
      two SD below the population mean. Serum concentrations of 1,25
      dihydroxycholecalciferol and osteocalcin both correlated significantly with bone
      density (p < 0.05) and there was a strong correlation between serum osteocalcin
      and serum intact parathyroid hormone (p < 0.001). Serum osteocalcin had the
      strongest correlation with bone density of any of the biochemical variables.
      CONCLUSION: There is little association between bone density and serum
      concentration of parathyroid hormone.

PMID- 1358214
TI  - Effect of perioperative blood transfusion and cell saver on the incidence of
      postoperative infective complications in patients with an aneurysm of the
      abdominal aorta.
AB  - OBJECTIVE: To find out if there was an association between perioperative blood
      transfusion and the development of infective complications, and whether the use
      of the cell saver for autologous transfusion had any influence. DESIGN:
      Retrospective study. SETTING: University Hospital. SUBJECTS: 102 consecutive
      patients who had been operated on for aneurysms of the abdominal aorta. MAIN
      OUTCOME MEASURES: Morbidity and mortality. RESULTS: 32 of the 102 patients
      developed infective complications. Thirteen patients died (six after emergency
      and seven after elective operations). Nine died as a direct result of infection,
      one of intra-abdominal bleeding, one of necrosis of the colon, and two of
      cardiopulmonary complications. The incidence of infective complications was
      directly related to the number of units of blood transfused, being 0 when 0 or 1
      was given; 11 (20%) when 2-4 units were given; 12 (55%) when 5-8 units were
      given; and 9 (69%) when the number was 9 or more. The cell saver had no influence
      on the incidence. Other factors associated with higher rates of infective
      complications were the insertion of a bifurcated prosthesis (p = 0.03), and
      emergency operation (p < 0.001). CONCLUSION: These results confirm the
      association between blood transfusion and the incidence of infective
      complications. It may be that more intensive use of the cell saver and
      preoperatively saved autologous blood could reduce the rate of infective
      complications.

PMID- 1358215
TI  - Fibrin sleeve formation after long term brachial catheterisation with an
      implantable port device. A prospective venographic study.
AB  - OBJECTIVE: To evaluate the risk of thrombosis after long term venous access with
      an implantable port device (PAS-Port system). DESIGN: Open study. SETTING:
      University Hospital, Linkoping, Sweden. SUBJECTS: Sixteen patients who required
      central venous catheters for long term chemotherapy were prospectively followed
      for 218 patient months (median 12.5 months/patient, range 3-34). INTERVENTIONS:
      Venogram taken while the catheters were being withdrawn. Venography was also done
      in 10 patients 1-29 months after the catheter had been removed. RESULTS: The
      venograms showed that fibrin sleeves had developed along the route of the
      catheter in all cases (cubital vein to the superior vena cava n = 7; to
      subclavian vein alone n = 8; and basilic vein alone n = 1). One of the 10
      patients who underwent venography 1-29 months later had developed an occlusive
      subclavian vein thrombosis with well developed collateral vessels 10 months after
      the catheter had been removed. CONCLUSION: Because of the high incidence of
      formation of extensive fibrin sleeves, implantable port devices should be removed
      as soon as they have served their purpose. If catheters malfunction they should
      be evaluated radiographically.

PMID- 1358216
TI  - Combined sclerotherapy and operation for the treatment of bleeding oesophageal
      varices.
AB  - OBJECTIVE: To identify prognostic factors in a consecutive series of patients
      with bleeding oesophageal varices and develop an optimum regimen of treatment.
      DESIGN: Retrospective review. SETTING: I Department of Surgery, University
      Hospital, Vienna, Austria. PATIENTS: 301 consecutive patients with bleeding
      oesophageal varices. OUTCOME MEASURES: Median survival and survival at one year
      after sclerotherapy alone (n = 213), or sclerotherapy with portosystemic shunt (n
      = 54), Hassab's devascularisation (n = 29), or liver transplantation (n = 5).
      RESULTS: Prognosis was dependent on the severity of liver damage at the start of
      treatment. Median survival for Child's class A was 47 months, for Child's class B
      54 months, and for Child's class C 2 months. The overall one year survival for
      patients in Child's class C was 33%, for sclerotherapy alone 28%, and for
      sclerotherapy and portosystemic shunt 42%, Hassab's devascularisation 50%, and
      liver transplantation 80%. CONCLUSION: Despite the small number of patients who
      underwent liver transplantation and their poor initial prognosis (Child's class
      C, n = 4; class B, n = 1) our results suggest that liver transplantation should
      be considered for the treatment of patients with end stage cirrhosis and bleeding
      varices.

PMID- 1358217
TI  - Association between permeability of the colonic wall and azoxymethane induced
      cancer of the colon in rats.
AB  - OBJECTIVE: To investigate the association between colonic permeability and the
      development of azoxymethane induced colonic cancer in rats. MATERIAL: Seventy
      three male Fischer-Cooper hybrid rats. INTERVENTIONS: Measurement of the
      concentrations of sodium fluorescein in plasma as an indication of its passage
      across the bowel wall in control rats, and six weeks and six months after
      injection of azoxymethane. RESULTS: Forty-seven rats were given azoxymethane, and
      26 acted as controls. Sodium fluorescein was instilled into segments of right (n
      = 46) and left (n = 27) colon and measured in peripheral blood; significantly
      higher concentrations were recorded after instillation into the left than into
      the right colon. No tumours developed in the 15 rats that were given azoxymethane
      and were examined after six weeks. At six months, however, 29 of the remaining 32
      had developed 94 macroscopic tumours (range 1-12 tumours/rat), and 89 of these
      (95%) were in the left colon. CONCLUSION: The greater permeability of the left
      colon in rats compared with the right may be associated with the higher incidence
      of carcinomas in the left compared with the right colon.

PMID- 1358218
TI  - Morbidity after immediate and delayed opening of sigmoid end colostomy: a
      randomised trial.
AB  - OBJECTIVE: To see if sigmoid end colostomies that were opened immediately carried
      a higher early morbidity than those in which opening was delayed for 10 days.
      DESIGN: Randomised trial. SETTING: University department of surgical
      gastroenterology. SUBJECTS: All patients for whom a temporary or permanent end
      sigmoid colostomy was done between December 1986 and May 1989. INTERVENTIONS: 51
      patients had their colostomies opened immediately, and in 49 opening was delayed.
      MAIN OUTCOME MEASURES: Presence of ischaemia, retraction, separation or
      infection, and length of stay in hospital. RESULTS: Two patients from each group
      died within the first week; none of the deaths was associated with complications
      of the colostomy. One patient whose colostomy had been opened immediately
      developed gangrene of the stoma, and one in whom the opening had been delayed
      developed retraction. There was no difference between the groups in length of
      stay in hospital. CONCLUSION: As we could find no differences in morbidity
      whether the colostomy was opened immediately or whether it was delayed, we now
      recommend that it should be done immediately. The question of late complications
      (stenosis and hernia), however, cannot be answered yet.

PMID- 1358220
TI  - Haemangiomas of the breast in children.
AB  - Capillary hemangioma of the breast parenchyma is a rare finding in the pediatric
      age group. The condition was diagnosed in two children, aged 18 months and three
      years. Such lesions have occasionally been found during histologic surveys among
      asymptomatic adult women. Although vascular tumors in the adult breast are often
      found to be sarcomatous, the pediatric lesion is benign and responds well to
      simple excision.

PMID- 1358219
TI  - Maximum anal sphincter strength measured by the solid sphere test and anal
      pressure profiles.
AB  - OBJECTIVE: To evaluate two methods of quantifying external anal sphincter
      function. DESIGN: Open study. SETTING: Helsingborg Hospital, Sweden. SUBJECTS: 73
      patients (63 women and 10 men), of whom 25 were incontinent of gas and liquid or
      solid stool. INTERVENTIONS: Anal pressure profiles and the "solid sphere" test.
      OUTCOME MEASURE: Correlation between results of tests and presence of
      incontinence. RESULTS: Continent patients were younger than incontinent ones. The
      correlation between the maximum force the patient could retain and the maximum
      anal squeeze pressure was good (r = 0.67, p < 0.001). Younger continent patients
      (n = 48) and significantly higher pressures than incontinent patients (n = 25),
      but the range and overlap were wide. The reproducibility of both methods was
      good. CONCLUSIONS: Although the solid sphere test is easier and quicker to do,
      anal pressure profiles yield more information that is important in the evaluation
      of incontinence.

PMID- 1358222
TI  - Blunt oesophageal perforation: treatment with surgical exclusion and percutaneous
      drainage under computed tomographic guidance.

PMID- 1358221
TI  - Perforated diverticulum of the appendix.

PMID- 1358223
TI  - Acute chylous effusion with peritonism.

PMID- 1358224
TI  - Regional intra-arterial thrombolytic treatment of venous gangrene of the foot.

PMID- 1358225
TI  - Enterocolitis in Behcet's syndrome.

PMID- 1358226
TI  - Trophic effects of neurotransmitters during brain maturation.
AB  - Besides their neurotransmitter and/or neuromodulatory roles, many neuroactive
      substances synthesized and released during brain development can also directly
      influence neuronal differentiation. Transitory expression of neurotransmitters,
      their metabolic enzymes and their receptors is only one aspect of this trophic
      role. The most considerable progress in neurotrophic factor research has been
      made with the use of primary cultures of neuronal cells, and numerous studies
      have focused on the effects of neurotransmitters on the differentiation of cells
      at various stages of development. Thus, several neuropeptides like VIP, substance
      P, enkephalins, somatostatin, and monoamines, can modulate neuronal
      differentiation, but only during a limited period of fetal life. Among the
      monoamines, it was shown that, depending on the target, 5-HT stimulates the
      development of the neuropile, the myelinization of axons, the differentiation of
      the synaptic contacts, induces markers of monoaminergic neuron differentiation,
      inhibits the development of the growth cone, decreases the branching of neurites,
      and influences the survival, cell body size, and neurite outgrowth in several
      neuronal cultures. 5-HT can also indirectly influence the differentiation of
      serotonergic neurons by the intermediate of astrocytes, and it was shown in our
      laboratory that 5-HT1A agonists can stimulate the cholinergic parameters of
      primary cultures of rat fetal septal neurons. At the molecular level, the events
      triggered by neurotransmitters that underlie their neurotrophic action probably
      involve the transmembrane influx of calcium. To date, calcium regulation of
      cellular processes is one of the most rapidly expanding areas of research in
      developmental neurobiology.

PMID- 1358227
TI  - International Symposium on Fetal and Neonatal Neurology. Tours, October 7-10,
      1992.

PMID- 1358228
TI  - Role of excitatory amino acid antagonists in the management of birth asphyxia.
AB  - Birth asphyxia is an important cause of permanent neuro-developmental disability.
      Asphyxia sets in course a progression of intracellular events which culminates in
      neuronal death, and this process may take up to 48 h to complete. Entry of
      calcium into the neurone appears to be the key to the cell death, and it is known
      that during asphyxia, excessive glutamate is released which stimulates the
      voltage-dependent N-methyl-D-aspartate (NMDA) receptor to open with an
      accumulation of excess intracellular calcium. MK-801 is a very effective NMDA
      receptor antagonist, and it has been shown that this drug prevents or
      significantly reduces the extent of cortical neurone infarction following
      experimental asphyxia in 7-day-old rat pups. Unfortunately, MK-801 is toxic to
      the pup, but newer NMDA receptor antagonists may offer the opportunity for
      neuroprotection in the human infant who has suffered severe birth asphyxia.

PMID- 1358229
TI  - Single photon emission tomography assessment of cerebral dopamine D2 receptor
      blockade in schizophrenia.

PMID- 1358230
TI  - Dynamical systems in psychiatry: now what?

PMID- 1358231
TI  - GABA agonist-induced changes in motor, oculomotor, and attention measures
      correlate in schizophrenics with tardive dyskinesia.
AB  - Saccadic distractibility, Stroop color-word scores, and serial dyskinesia
      assessments were obtained on 10 schizophrenic patients with tardive dyskinesia
      during a pharmacologic challenge with placebo or 7 mg muscimol, a potent, direct
      acting GABA agonist. Although no significant difference in the measures was
      evident between conditions, a significant correlation was found between GABA
      agonist-induced changes in saccadic distractibility and dyskinesia scores where
      no correlation existed between these measures on placebo. Improvement in saccadic
      distractibility was also correlated with reduction in attention performance, as
      measured by Stroop. These effects are not due to sedation. The correlation
      between dyskinesia and saccadic distractibility is consistent with a model of
      parallel motor and oculomotor cortico-striatal-thalamic circuits in humans. This
      work supports the hypothesis that a dysfunction in GABA-mediated
      neurotransmission may be the basis for tardive dyskinesia.

PMID- 1358233
TI  - The effect of alpha-1-adrenoreceptor agonist and antagonist administration on
      human upper gastrointestinal transit and motility.
AB  - To explore the role of alpha-1-adrenoreceptor-mediated pathways on human upper
      gut motor function in vivo, we studied the effects of the alpha-1-agonist
      phenylephrine and the alpha-1-antagonist thymoxamine on oro-caecal transit and
      antroduodenal motor activity. Transit was measured using a standard exhaled
      breath hydrogen method, and motility was measured by intraluminal manometry. Oro
      caecal transit was unaffected by 80 mg thymoxamine [median 63 min (range 35-164
      min) vs. control, 65 min (range 30-155 min), P greater than 0.1]. However,
      phenylephrine (2.4 micrograms/kg/min) consistently delayed oro-caecal transit
      time to 103 min (50-215 min), P greater than 0.005. Co-administration of
      thymoxamine abolished this phenylephrine-induced delay. The mean amplitude of
      antral postprandial contractions was reduced by phenylephrine from 29 (13-37) to
      10 (3-13) mmHg (P less than 0.02). In contrast, neither the pattern nor the mean
      inter-contraction interval was altered. Responses to phenylephrine in the
      duodenum were similar to those in the antrum, with reduction in amplitude from 12
      (3-18) to 6 (5-13) mmHg without alteration in the pattern or interval between
      contractions. Nutrient transit through the upper gut can thus be inhibited via
      activation of an alpha-1-adrenoreceptor-mediated pathway. Failure of alpha-1
      antagonist administration to alter oro-caecal transit suggests that this pathway
      is not tonically active, and it is therefore unlikely to play a major role in
      nutrient passage under normal circumstances.

PMID- 1358232
TI  - Cyclic GMP modulators on vascular adrenergic neurotransmission.
AB  - The presence of the endothelium reduced the sensitivity of isolated rabbit
      carotid artery to endogenous norepinephrine released by electrical stimulation of
      adrenergic nerves or displaced by tyramine and to exogenously applied
      norepinephrine, phenylephrine and UK 14304. The maximal contractions induced by
      the selective alpha 2-agonist UK 14304 were much more profoundly depressed in
      arteries with endothelium than those induced by the nonselective alpha
      adrenoceptor agonist norepinephrine or by the selective alpha 1-agonist. LY
      83583, a cyclic-guanosine-monophosphate (GMP)-lowering agent, abolished the
      endothelium-dependent depression of tone induced by the agonists and converted
      the sensitivity of arteries with endothelium to that of endothelium-denuded
      preparations. M & B 22948, a selective cyclic GMP phosphodiesterase inhibitor,
      significantly inhibited contractions caused by electrical stimulation of
      adrenergic nerves, tyramine, norepinephrine and UK 14304 in rings with, but not
      in those without, endothelium. Yohimbine, an alpha 2-adrenoceptor antagonist,
      increased contractions caused by UK 14304 in rings with endothelium only, but had
      no significant effect on the contractions caused by exogenously applied
      norepinephrine or phenylephrine. In the presence of prazosin, an alpha 1-blocker,
      UK 14304 caused minimal relaxation (about 20%) in rings with endothelium only
      which were inhibited by yohimbine, suggesting a minor role of direct endothelial
      cell alpha 2-mediated release of relaxing factors. The over-flow of endogenous
      norepinephrine caused by electrical stimulation was not affected by treatment
      with LY 83583 or M & B 22948, suggesting that altering cyclic GMP levels has no
      major role in prejunctional modulation of norepinephrine release. These findings
      support the notion that intrinsic levels of cyclic GMP may act as a regulator of
      adrenergic neurotransmission due primarily to endothelium-derived relaxing factor
      which is released basally, and to a lesser extent by an activation of endothelial
      cell alpha 2-adrenoceptors.

PMID- 1358235
TI  - The effect of H2-blockade on plasma gastrin concentration in patients with an
      achlorhydric stomach.
AB  - The mechanisms of hypergastrinaemia during H2-receptor antagonist therapy remain
      unclear. In addition, the effect of food stimulation in conditions of
      hypergastrinaemia is poorly understood. These effects may be important when
      considering long-term therapy with potent acid inhibitory agents. To investigate
      this we studied the effect of H2-receptor antagonist therapy on basal and meal
      stimulated plasma gastrin concentrations in 9 patients with pentagastrin fast
      gastric achlorhydria associated with pernicious anaemia. The subjects received in
      double-blind randomized fashion 28-day courses of 300 mg ranitidine q.d.s. and
      placebo, with one-month wash-out between. The fasting and peptone meal-stimulated
      gastrin concentrations were studied on the final day of each course of treatment.
      The median fasting gastrin concentrations (ng/L) were similar following placebo
      (1100, range 25-2100), and 300 mg ranitidine q.d.s. (1075, range 15-2600) and
      both markedly elevated when compared with our laboratory's normal range of 0-100.
      Despite the elevated basal levels the pernicious anaemia patients still showed a
      further increase in response to the peptone meal. Their median peak percentage
      rise over basal in response to the meal was similar following placebo (96%, range
      0-375) and 300 mg ranitidine q.d.s. (100%, range 25-425) (both P less than 0.02
      c.f. basal). This study shows that: (a) in hypergastrinaemia in pernicious
      anaemia subjects, meal stimulation leads to a marked and prolonged increase in
      plasma gastrin concentrations; (b) H2-receptor antagonists have no effect on
      plasma gastrin in the neutral stomach and this is consistent with their gastrin
      effect being entirely secondary to acid inhibition.

PMID- 1358234
TI  - Improved maintenance of remission in ulcerative colitis by balsalazide 4 g/day
      compared with 2 g/day.
AB  - The efficacy of two doses of balsalazide for the maintenance of remission in
      patients with ulcerative colitis was compared in a double-blind multicentre
      trial. Sixty-five patients received a 2 g daily dose, and 68 a 4 g dose. The
      patient groups were similar at entry for sex, age, and disease distribution.
      Clinical assessment was carried out at 3-monthly intervals, with sigmoidoscopy,
      rectal biopsy, and blood tests on entry and at 26 and 52 weeks. Clinical relapse
      over twelve months was significantly less common on the 4 g dose (36%), than on
      the 2 g dose (55%), P less than 0.01. There were eight withdrawals on 2 g daily
      and 13 on 4 g daily, six and nine respectively being mainly due to
      gastrointestinal intolerance. It is concluded that balsalazide is a well
      tolerated drug, and is effective for the maintenance of remission in patients
      with ulcerative colitis, the optimal dose being greater than 2 g daily.

PMID- 1358237
TI  - Thyroid autoimmunity. International symposium proceedings. Montreal, Canada,
      September 1991.

PMID- 1358236
TI  - [The use of narcotic analgesics in primary care in Spain (1988-1991). An
      evaluation of the impact of new technologies in the pharmaceutical sector].
AB  - OBJECTIVE: To analyse the results of the policy of encouraging rational use of
      analgesics in Spain. DESIGN: Longitudinal retrospective and observational study,
      on the exhaustive information deriving from the filling out of Analgesic Extra
      therapeutic Dose notebooks. SITE. Primary Care treatment of terminal oncological
      patients carried out basically in the Province of Barcelona. PARTICIPANTS: All
      treatments carried out under the extra-therapeutic dose notebook during the last
      quarter of 1988 and the first quarters of 1989, 1990, and 1991. MAIN MEASUREMENTS
      AND RESULTS: Revision of initial treatment, change of medication and posology and
      returns on the basis of the extensive documentation generated. Consumption has
      risen from 157 authorized cases in 1989 to 404 in 1991. CONCLUSIONS: Consumption
      has increased sharply, although the opinion that such analgesics are under-used
      still predominates. Along with the quantitative increase there has been a
      corresponding deterioration in the rationale informing use and control, both
      medically (patterns of treatment, excesses) and socially (cost effectiveness,
      fair allocation). The evaluation in force before the advent of new technology and
      policies should be reinstated if we wish to achieve the desired level of
      effectiveness, adapting national health care by coordinating social and health
      care and bringing up to standard the training and supply of information to health
      workers. It is suggested that a "Consensus" Conference should be organised to
      bring up to date the basis on which analgesics are used and regulated.

PMID- 1358238
TI  - Protein kinase C as a mediator of TSH and thyroid autoantibody action.
AB  - Although it is well-established that TSH activates a cAMP-dependent pathway in
      the thyroid follicular cell leading to thyroid hormone synthesis and release, the
      present review provides new evidence that TSH also activates a non-cAMP-dependent
      signal transduction system. This cascade involves phosphoinositide (PI) turnover,
      diacylglycerol accumulation and protein kinase C (PKC) activation. Activation of
      this pathway leads to an inhibition of differentiated thyroid function in vitro.
      Recent evidence suggests that TSH can activate both pathways via a single
      transcription unit. Unlike TSH, TSH-receptor antibodies may selectively activate
      cAMP with no effects on PI turnover. In contrast, preliminary studies suggest TSH
      blocking antibodies may activate PKC. PKC may be an important mediator of TSH
      and, possibly, thyroid autoantibody action.

PMID- 1358240
TI  - The effect of second-line antirheumatic drugs on interleukin-8 mRNA synthesis and
      protein secretion in human endothelial cells.
AB  - Interactions between interleukin 8 (IL-8) and endothelial cells play an important
      role in the emigration of mononuclear cells from the blood into areas of
      inflammation. We examined the ability of specific second-line antirheumatic drugs
      to regulate (IL-8) gene expression and protein secretion in interleukin 1 (IL-1)
      stimulated human umbilical vein endothelial cells and peripheral blood
      mononuclear cells. The drugs sodium aurothiomalate, D-penicillamine and
      sulphasalazine were all able to modulate IL-8 mRNA synthesis in and protein
      secretion from endothelial cells. A bimodal effect was observed: at low
      concentrations IL-8 was suppressed, whereas higher concentrations resulted in an
      increased IL-8 production. In endothelial cells, treatment with hydrocortisone
      led to a linear suppression of IL-8 production in concentrations ranging from 0.5
      micrograms/ml up to 500 micrograms/ml. Sulphapyridine, auranofin,
      hydroxychloroquine and methotrexate, had no effect on IL-8 secretion in
      endothelial cells. By contrast, 5-aminosalicylic acid induced a threefold
      increase in the IL-8 release. In peripheral blood mononuclear cells it was only
      possible to suppress the IL-8 production by hydrocortisone treatment. These
      results indicate that suppression of IL-8 production in endothelial cells could
      be an important factor in the mode of action for a number of second-line
      antirheumatic drugs.

PMID- 1358239
TI  - Micromanipulation of adhesion of phorbol 12-myristate-13-acetate-stimulated T
      lymphocytes to planar membranes containing intercellular adhesion molecule-1.
AB  - This paper presents an analytical and experimental methodology to determine the
      physical strength of cell adhesion to a planar membrane containing one set of
      adhesion molecules. In particular, the T lymphocyte adhesion due to the
      interaction of the lymphocyte function associated molecule 1 on the surface of
      the cell, with its counter-receptor, intercellular adhesion molecule-1 (ICAM-1),
      on the planar membrane, was investigated. A micromanipulation method and
      mathematical analysis of cell deformation were used to determine (a) the area of
      conjugation between the cell and the substrate and (b) the energy that must be
      supplied to detach a unit area of the cell membrane from its substrate. T
      lymphocytes stimulated with phorbol 12-myristate-13-acetate (PMA) conjugated
      strongly with the planar membrane containing purified ICAM-1. The T lymphocytes
      attached to the planar membrane deviated occasionally from their round
      configuration by extending pseudopods but without changing the size of the
      contact area. These adherent cells were dramatically deformed and then detached
      when pulled away from the planar membrane by a micropipette. Detachment occurred
      by a gradual decrease in the radius of the contact area. The physical strength of
      adhesion between a PMA-stimulated T lymphocyte and a planar membrane containing
      1,000 ICAM-1 molecules/micron 2 was comparable to the strength of adhesion
      between a cytotoxic T cell and its target cell. The comparison of the adhesive
      energy density, measured at constant cell shape, with the model predictions
      suggests that the physical strength of cell adhesion may increase significantly
      when the adhesion bonds in the contact area are immobilized by the actin
      cytoskeleton.

PMID- 1358242
TI  - Systemic hyperthermia in the treatment of HIV-related Kaposi's sarcoma. A phase I
      study.
AB  - Ten Caucasian males with HIV-related Kaposi's sarcoma, a disseminated disease
      which is refractory to usual therapies, underwent a single session of systemic
      hyperthermia with maintenance of core temperatures at 42 degrees C for 1 h. One
      complete remission and 7 partial remissions were identified when assessed 30 days
      post-treatment. Two mixed responses were noted in patients whose tumors showed
      autocrine growth. At 60 days 2 of the 7 partial responders began to show tumor
      progression. The complete remission persisted at 120 days. Surrogate markers of
      HIV activity fell in all responding patients. In no patient was there evidence of
      HIV activation. No adverse effects of heating were noted on CMV retinitis. Hairy
      leukoplakia resolved with heating in all patients. CD4 counts showed no
      appreciable change in any of the 8 patients with a presenting CD4 count below 60.
      In the 2 patients who presented with a CD4 count above 400, CD4 counts rose
      dramatically following treatment. No deaths were noted in this phase I study. The
      use of systemic hyperthermia in treatment of HIV-related illness warrants further
      study.

PMID- 1358241
TI  - Upregulation of HLA class II, but not intercellular adhesion molecule 1 (ICAM-1)
      by granulocyte-macrophage colony stimulating factor (GM-CSF) or interleukin-3 (IL
      3) in synergy with dexamethasone.
AB  - In this study we have compared the effects of granulocyte macrophage colony
      stimulating factor (GM-CSF) on purified normal blood monocytes, with two other
      haemopoietic growth factors, Interleukin (IL-) 3 and Macrophage (M-)CSF on HLA
      class I, class II and intercellular adhesion molecule 1 (ICAM-1) expression in
      the presence and absence of dexamethasone (Dex). IL-3 alone, like GM-CSF, was a
      weak inducer of HLA class II expression but in combination with Dex markedly
      enhanced HLA-DR, DP and DQ expression. Similar changes were observed for HLA
      class I expression. The response to both IL-3 and GM-CSF was not additive in the
      presence of an optimal concentration of one cytokine and titrating concentrations
      of the other indicating that they may use common receptors and signal
      transduction mechanisms. Although IL-3 or GM-CSF alone also enhanced ICAM-1
      expression, Dex inhibited both constitutive and the cytokine induced expression
      of this antigen. In contrast M-CSF, in the presence or absence of Dex, failed to
      enhance ICAM-1, HLA class I or II expression. These observations further
      highlight differences between the effects of the haemopoietic growth factors GM
      CSF and IL-3 versus M-CSF in the regulation of monocyte function. Finally, the
      distinct effect of a combination of glucocorticoids with GM-CSF or IL-3 to induce
      high levels of HLA expression on human monocytes suggests they may have an
      important role during inflammatory conditions in vivo.

PMID- 1358243
TI  - Pharmacokinetics of alfuzosin after single oral administration to healthy
      volunteers, of three different doses.
AB  - The aim of this study was to assess the linearity of pharmacokinetic of
      alfuzosin, administered by oral route, at the doses of 1, 2.5, and 5 mg to 12
      young healthy volunteers. The pharmacokinetic parameters (tmax, Cmax, AUC, t1/2
      beta) obtained from plasma alfuzosin concentrations after administration of the
      three doses show that pharmacokinetics of alfuzosin is linear in the range of
      doses 1-5 mg. Mean pharmacokinetic parameters of alfuzosin observed after 1, 2.5,
      and 5 mg were, respectively: tmax (h) 1.5 +/- 0.3, 1.1 +/- 0.2, 1.3 +/- 0.1; Cmax
      (ng ml-1) 2.6 +/- 0.3, 9.4 +/- 1.2, 13.5 +/- 1.0; AUC (ng ml-1 h) 17.7 +/- 2.9,
      51.7 +/- 7.1, 99.0 +/- 14.1; t1/2 (h) 3.7 +/- 0.4, 3.9 +/- 0.2, 3.8 +/- 0.3. Cmax
      (corrected by the dose) obtained after 2.5 mg was significantly higher than those
      obtained after 1 and 5 mg. This difference seems to be due principally to the
      intraindividual variability. The absence of statistically significant difference
      on individual values of AUC corrected by the administered dose, supports the
      linearity of the pharmacokinetics of alfuzosin in the range of doses between 1
      and 5 mg. Some postural hypotension, clinical criterion, was observed with a
      frequency increasing with the dose in these healthy subjects: 0 volunteers of 12
      after 1 mg, 3 volunteers of 12 after 2.5 mg and 4 volunteers of 12 after 5 mg.

PMID- 1358244
TI  - The metabolism of CGS 15873 in man using stable isotope pattern recognition
      techniques.
AB  - CGS 15873 is a relatively specific dopamine agonist with preferential activity at
      the presynaptic autoreceptor and therefore may represent a novel agent for the
      treatment of schizophrenia and/or Parkinson's disease. Several metabolites have
      been identified in the rat and monkey using an isotopically enriched dosing
      solution and pattern recognition techniques coupled with GC/MS and LC/MS. In this
      study, the metabolism of CGS 15873 was investigated in man using these same
      techniques. In urine, specific isotope clusters were found that matched the
      dosing solution pattern. Three metabolites were identified: an O-glucuronide
      conjugate of the parent drug, N-despropyl CGS 15873, and a keto metabolite of CGS
      15873. Thermospray LC/MS allowed for the direct confirmation of the conjugated
      metabolite. GC/MS required derivatization but afforded greater sensitivity
      compared to LC/MS.

PMID- 1358245
TI  - Immunoprecipitation of a pertussis toxin substrate of the G(o) family from rat
      islets of Langerhans.
AB  - Rat islets express a pertussis toxin sensitive G-protein involved in receptor
      mediated inhibition of insulin secretion. This has been assumed previously to
      represent "G(i)" which couples inhibitory receptors to adenylate cyclase.
      Incubation of islet G-proteins with 32P-NAD and pertussis toxin resulted in the
      labelling of a band of molecular weight 40,000. This band was very broad and did
      not allow resolution of individual components. Incubation of the radiolabelled
      proteins with an anti-G(o) antiserum resulted in specific immunoprecipitation of
      a 32P-labelled band. These results demonstrate that the complement of pertussis
      toxin sensitive G-proteins in rat islets includes G(o).

PMID- 1358246
TI  - Voltage-gated calcium channels in adult hippocampal neurons.

PMID- 1358247
TI  - Prolonged infusion of varied doses of dopexamine hydrochloride for low cardiac
      output after cardiac surgery.
AB  - Circulatory failure after cardiac surgery often calls for active hemodynamic
      management with fluids, inotropes, and vasodilators. Dopexamine hydrochloride is
      a new combined beta 2-adrenergic and DA1-dopaminergic receptor agonist and an
      inhibitor of the uptake-1 mechanism of endogenous catecholamines. As a result, it
      exerts inotropic and vasodilator effects on the heart and systemic vasculature.
      The effects were examined over a mean of 22 hours, using 1 to 4 micrograms/kg/min
      of dopexamine to treat low cardiac output states following coronary bypass and
      valvular/ventricular repair surgery. In 8 out of 14 patients, low cardiac output
      was readily reversed by 1 microgram/kg/min of dopexamine. Six patients required
      higher doses (2 to 4 micrograms/kg/min) to achieve a satisfactory cardiac index.
      Significant changes from control values were observed throughout the infusion for
      heart rate (67 to 102 beats/min), cardiac index (2.0 to 3.4 L/min/m2), and
      systemic vascular resistance (1,545 to 914 dyne.s.cm-5). Pulmonary vascular
      resistance, pulmonary artery wedge pressure, and right atrial pressure were also
      significantly reduced during the infusion. Most of these changes reversed when
      dopexamine was discontinued, suggesting a drug-specific effect and a lack of
      tolerance. Nausea was a frequent complaint, but was no more frequent than in a
      random sample of similar patients. Titration of dopexamine, 1 to 4
      micrograms/kg/min, was efficacious in producing circulatory improvement in
      patients with a low cardiac output after cardiac surgery.

PMID- 1358248
TI  - Esmolol for the treatment of isorhythmic atrioventricular dissociation.

PMID- 1358249
TI  - Case 6-5--1992. Anesthetic considerations for thoracoscopic procedures.

PMID- 1358250
TI  - Retinal on-bipolar cells contain a nitric oxide-sensitive guanylate cyclase.
AB  - Retinal on-bipolar cells possess specialized glutamate receptors which are
      coupled via a G-protein to the control of a cyclic GMP (cGMP) cascade. Whole-cell
      voltage clamp recordings were obtained from light-responsive on-bipolar cells in
      retinal slices of the dogfish. Inclusion of nitroprusside in the patch-pipette
      solution induced effects in on-bipolar cells which were consistent with a rise in
      intracellular cGMP and thus stimulation of guanylate cyclase (GC) activity.
      Conversely, the soluble GC inhibitors, methylene blue and ferricyanide, induced
      effects consistent with a fall in intracellular cGMP. Activators of particulate
      GC had no effect. We conclude that cGMP synthesis in on-bipolar cells is
      catalysed by a NO-sensitive cyclase.

PMID- 1358251
TI  - Enrichment of glutamate in zinc-containing terminals of the cat visual cortex.
AB  - The presence of glutamate and GABA was examined in zinc-containing terminals of
      the cat visual cortex using a post-embedding immunogold method. The surface
      density of immunogold-labelling was also evaluated in morphologically defined
      ultrastructural elements, namely terminals having round synaptic vesicles and
      making asymmetrical synapses (RA boutons), terminals with flat vesicles and
      symmetrical synapses (FS) and glial cell processes. Glutamate immunoreactivity
      was highest in RA terminals and in zinc-containing boutons. It was lower in FS
      terminals and lowest in glial cell processes. GABA immunoreactivity was highest
      in FS terminals and low in all other ultrastructural elements analysed, including
      zinc-containing terminals. Therefore, zinc-containing terminals show an
      enrichment of glutamate and they are likely to use this amino acid as their
      neurotransmitter. Moreover, the fact that many RA terminals that are negative for
      zinc show an enrichment of immunoreactive glutamate suggests that zinc-containing
      fibres represent a subpopulation of the glutamate axonal network.

PMID- 1358253
TI  - Antianxiety properties of the angiotensin II antagonist, DUP 753, in the rat
      using the elevated plus-maze.
AB  - The angiotensin II receptor antagonist, DUP 753 (Losartan), was compared with
      diazepam for antianxiety properties in the rat using the elevated plus-maze. Oral
      diazepam (5 mg kg-1) resulted in a significantly greater number of entries of
      rats into the open arms of the maze, an increase in time spent in the open arms
      and a decreased time spent in the closed arms. Oral doses of DUP 753 likewise
      resulted in significantly greater numbers of entries into the open arms (active
      at 0.0001, 0.001, 0.01 and 0.1 mg kg-1), increased time spent on the open arms
      (active at 0.0001-0.01 mg kg-1) and a decreased time spent in the closed arms
      (active at 0.0001, 0.01 and 0.1 mg kg-1). Larger (1.0 mg kg-1) or smaller
      (0.00001 mg kg-1) doses of DUP 753 were not active.

PMID- 1358252
TI  - Cholecystokinin is released from a crossed corticostriatal pathway.
AB  - The release of striatal cholecystokinin, glutamate, aspartate and dopamine was
      studied in vivo with microdialysis in decorticated rats, with or without
      callosotomy. Unlesioned rats were also analysed. Unilateral decortication
      produced a unilateral decrease in K(+)-stimulated extracellular striatal
      glutamate and aspartate levels, without decreasing cholecystokinin or dopamine
      levels. However, following decortication plus callosotomy, basal and K(+)
      stimulated extracellular cholecystokinin and glutamate levels were significantly
      decreased in the striatum ipsilateral to side of decortication. Aspartate levels
      were bilaterally decreased. These results give evidence for the existence of
      crossed corticostriatal projections containing releasable cholecystokinin and
      glutamate.

PMID- 1358254
TI  - Differential distribution of gamma-glutamyl cycle molecules in the vomeronasal
      organ of rats.
AB  - Molecules related to the gamma-glutamyl cycle, including thiols, glutathione
      (GSH) and gamma-glutamyl transpeptidase (gamma-GT) were identified
      histochemically and immunohistochemically in the vomeronasal organ of neonatal
      and adult rats. Thiols and GSH were distributed in the mucomicrovillar complex
      (MMC), vomeronasal receptor neurons and acinar cells of vomeronasal glands (VNG).
      gamma-GT was localized in the MMC and in the VNG, where it was associated mainly
      with the luminal surface of the acinar cells and ducts. The VNO of the neonates
      exhibited higher staining intensities for all compounds than that of the adults.
      The data indicate that components of the gamma-glutamyl cycle are present in the
      VNO and that they are secreted into mucus, where they may be associated with
      perireceptor events including clearance of pheromones and detoxification of
      xenobiotics.

PMID- 1358256
TI  - Calcium dynamics in neurons treated with toxic and non-toxic concentrations of
      glutamate.
AB  - Intracellular calcium concentration ([Ca2+]i) dynamics were simultaneously
      monitored in multiple cultured rat neurons loaded with Fluo-3 and continuously
      stimulated with glutamate (GLU). Three response types were observed: 10 microM
      GLU caused an initial transient increase in [Ca2+]i; 20 microM a biphasic
      response characterized by a 150-350 s 'calcium trough' between peaks; and 40
      microM an initial sustained increase in [Ca2+]i. Neurons in calcium-free medium
      treated with 40 microM GLU showed only an initial transient increase in [Ca2+]i,
      demonstrating the dependence of sustained secondary increases in [Ca2+]i on
      extracellular calcium sources. We observed synchronized responses of multiple
      neurons within a given culture well, after GLU treatment, supporting the
      hypothesis that sustained influx of extracellular calcium may be stimulated by
      depletion of intracellular calcium and/or the release of endogenous excitatory
      amino acids.

PMID- 1358255
TI  - Metabotropic glutamate receptor agonists potentiate a slow afterdepolarization in
      CNS neurons.
AB  - We have previously reported that, in the rat dorsolateral septal nucleus (DLSN),
      metabotropic glutamate receptor (met-GluR) agonists evoked a slow depolarization
      accompanied by an increase in membrane conductance and burst firing. We have
      speculated that the burst firing elicited by met-GluR agonists may be due to
      activation or enhancement of a non-specific cation current, which exists in some
      DLSN neurons. Now we report that a slow afterdepolarization (sADP) mediated by a
      non-specific cation current was potentiated by both 1S,3R-ACPD and quisqualate.
      In addition, met-GluR agonists unmask a sADP in DLSN neurons which did not show a
      sADP under control conditions. Our data suggest that a non-specific cation
      current can be potentiated by activation of the met-GluR.

PMID- 1358257
TI  - [Somatostatin as a modulator of vagal effects on heart rhythm].
AB  - In 11 experiments on anesthetised cats burst stimulation of peripheral cut end of
      right vagus nerve leads to synchronization of cardiac and vagus rhythms.
      Alterations of burst sequence frequency within definite limits has been
      synchronously reproduced by heart thus creating managed bradycardia possibility.
      Somatostatin (10(-8)-10(-9) M intravenously) decreases heart rate and inhibits
      total vagus chronotropic effect. Vagolytic effect of somatostatin caused a
      decrease of tonic component of the vagus chronotropic effect. On the other hand,
      somatostatin augmented the extent of the vagal synchronizing influences and
      caused enlargement of the ranges of managed bradycardia. The observed results
      testify to participation of the peptidergic mechanisms in genesis of vagal
      managed bradycardia.

PMID- 1358259
TI  - Homeobox genes in normal hematopoiesis and leukemia.

PMID- 1358258
TI  - [Different effects of typical and atypical neuroleptics on K+-stimulated dopamine
      release from isolated rat striatum].
AB  - Effects of haloperidol (10(-7)-alpha 10(-5) M), trifluoperazine, metoclopramide,
      tiapride, sulpiride, thioridazine, clozapine remoxipride, raclopride, cis- and
      trans-isomers of carbidine, SCH 23390 (all at the 10(-6) M) on the K(+)
      stimulated (28 mM) dopamine (DA) release from isolated rat striatum were studied.
      Haloperidol at the concentration of 10(-7) and 10(-6) M failed to affect, while
      at 10(-5) M the drug decreased the stimulated striatal DA release.
      Trifluoperazine, metoclopramide and tiapride were shown not to modify this
      process. Sulpiride, thioridazine, clozapine, remoxipride, raclopride, isomers of
      carbidine were found to increase significantly the stimulated striatal DA
      release. SCH 23390 failed to affect K(+)-stimulated release of DA in the striatum
      and also did not change K(+)-stimulated release enhancement produced by
      raclopride. It is suggested that the mechanism underlying observed effects of the
      drugs may contribute to pharmacological profile of atypical neuroleptics.

PMID- 1358260
TI  - Antilymphocytic antibodies and marrow transplantation. XII. Suppression of graft
      versus-host disease by T-cell-modulating and depleting antimouse CD3 antibody is
      most effective when preinjected in the marrow recipient.
AB  - A hamster antimouse CD3 monoclonal antibody (MoAb) opened the way to experimental
      studies on the suppression of allograft rejection and cytokine-related morbidity
      after treatment with antibodies modulating the CD3/T-cell receptor complex
      (CD3/TCR). Because earlier attempts to suppress graft-versus-host disease (GVHD)
      in patients by in vitro treatment of donor marrow with anti-CD3 MoAb had remained
      inconclusive, we used a rat IgG2b antimouse CD3 MoAb (17A2) with fewer side
      effects to analyze suppression of GVHD in the mouse model. Detailed phenotyping
      of blood, spleen, and lymphnode T cells after the injection of 400 micrograms
      17A2 in C57BL/6 mice showed 60% CD3 downmodulation and 50% T-cell depletion for
      spleen cells. Injection of these spleen cells, together with bone marrow cells,
      in fully mismatched preirradiated CBA mice delayed GVHD by only 6 days. Ex vivo
      treatment of donor cells with 17A2 was not effective. In contrast, conditioning
      of marrow recipients with a single injection of 17A2 delayed 50% GVHD mortality
      by 100 days and prevented GVHD altogether after prolonged treatment, with
      survivors showing complete chimerism and specific transplantation tolerance. This
      difference in antibody effect contrasts with earlier experiences with
      nonmodulating but more strongly T-cell-depleting MoAbs of the same isotype, which
      prevent GVHD no matter whether applied in vitro or injected into donor or
      recipient mice. Our data indicate that CD3/TCR reexpression in marrow recipients
      with no circulating 17A2 is the reason why ex vivo donor cell treatment with anti
      CD3 MoAb is comparatively ineffective. Our data, which allow separate evaluation
      of cell-depleting and cell-modulating antibody activity, help to explain previous
      clinical failure to suppress GVHD and provide evidence in favor of conditioning
      the marrow recipient with anti-CD3 MoAb as a therapeutic alternative.

PMID- 1358261
TI  - CD11c expression in chronic lymphocytic leukemia.

PMID- 1358262
TI  - A single cycle of 2-chlorodeoxyadenosine results in complete remission in the
      majority of patients with hairy cell leukemia.
AB  - Twenty-six patients with hairy cell leukemia (HCL) were treated with 2
      chlorodeoxyadenosine (2-CdA), a purine analogue resistant to adenosine deaminase,
      at 0.1 mg/kg/d for 7 days by continuous intravenous infusion. Fifteen patients
      were previously untreated, while 11 patients had received prior treatment with
      splenectomy alone (three patients), interferon alpha alone (four), splenectomy,
      then interferon alpha (two), or splenectomy, interferon alpha, then 2
      deoxycoformycin (2-DCF) (two). Sixteen (80%) of 20 patients evaluable at 3 months
      achieved complete remission (CR), and four (20%) achieved partial remission (PR)
      following a single cycle of therapy. All four patients in PR had complete
      recovery of their peripheral blood counts (except one patient whose platelet
      count remained 84,000/microL), but had residual HCL in the bone marrow (three
      patients) or residual splenomegaly (one). Patients with bulky adenopathy, massive
      splenomegaly, and severe pancytopenia responded as well as those with only modest
      marrow involvement. The three patients with residual marrow disease received a
      second cycle of 2-CdA, and two have attained CR. Therefore, 18 of 20 (90%)
      achieved CR with either one or two cycles of therapy. No patient achieving CR has
      relapsed at a median follow-up of 12 (+/- 2.1) months. Toxicities included
      myelosuppression and culture-negative fever. A community-acquired pneumonia was
      the only infectious complication. Since a single cycle of 2-CdA induces sustained
      CR in the vast majority of patients with minimal toxicity, this agent is emerging
      as the treatment of choice for all patients with HCL.

PMID- 1358263
TI  - Elevated levels of cICAM-1 in patients with human T-cell leukemia virus type I
      associated myelopathy and adult T-cell leukemia.

PMID- 1358264
TI  - Taxol: a review of its preclinical in vivo antitumor activity.
AB  - Taxol has been demonstrated in numerous laboratories worldwide to have broad
      spectrum antitumor activity against many tumor models. The susceptible tumors
      include murine leukemias and solid tumors, and human solid tumor xenografts. The
      initial findings of taxol's ineffectiveness against most distal site tumor models
      was probably a consequence of the insolubility of taxol in nearly all the
      vehicles used in those early studies. On the occasions when an ethanol-based
      vehicle was used to dissolve taxol, substantial distal site antitumor activity
      was observed. Although no definitive schedule dependency data have evolved, once
      a-day or every-other-day i.v. injections for several treatments have proved to be
      reproducibly effective in stringent s.c. tumor models. Attempts to discern a
      therapeutically synergistic cytotoxic drug combination was made on two occasions
      without success. In the manner evaluated, taxol plus either adriamycin,
      cisplatin, cyclophosphamide or etoposide (VP-16) were not meaningfully more
      efficacious than the more effective drug in each of those combination settings.

PMID- 1358265
TI  - Untoward reactions to gastric antisecretory drugs.

PMID- 1358266
TI  - Seasonality, biting cycle and parity of the yellow fever vector mosquito
      Haemagogus janthinomys in Trinidad.
AB  - 1. Age composition, seasonal abundance and diel patterns of landing activity of
      the sylvan vector of yellow fever Haemagogus janthinomys Dyar were monitored
      weekly during 1981-82 by human collectors on the ground at Point Gourde in
      Chaguaramas Forest, 16 km west of Port of Spain, Trinidad. 2. Landing collections
      of Hg. janthinomys showed only diurnal activity, from 06.00 to 18.00 (sunrise to
      sunset, universal time), with a single peak of activity between 10.00 and 16.00
      hours. 3. Densities of Hg. janthinomys were about 6 times greater during the wet
      season (May-November) than during the dry season (December-April); the annual
      Williams' mean landing rate on two collectors was 9.3 per day. 4. Monthly parous
      rates averaged 59% (range 0-86%) and some females were up to seven-pars. Retained
      eggs (range 1-21, mean 7.7/female) were found in the ovaries of 1.3% of landing
      females, all of which had stage I ovarian follicles for the next gonotrophic
      cycle. Hence blood-feeding is not inhibited by egg retention, which might promote
      transovarial transmission of virus. Implications of these findings are discussed
      in relation to yellow fever epidemiology.

PMID- 1358267
TI  - The susceptibility of the mosquitoes Aedes notoscriptus and Culex annulirostris
      to infection with dog heartworm Dirofilaria immitis and their vector efficiency.
AB  - The mosquitoes Aedes notoscriptus (Skuse) and Culex annulirostris Skuse were fed
      on a dog infected with Dirofilaria immitis (Leidy) and a blood parasite count of
      approximately 5000 microfilaria per ml. Cx annulirostris ingested almost 4 times
      as much blood and almost 4 times as many microfilariae as Ae.notoscriptus (mean
      26.0 compared to 6.6). Attrition of the filarial numbers occurred primarily
      within the midgut during the first 24 h following ingestion and was greater in Cx
      annulirostris than Ae.notoscriptus. Aedes notoscriptus sustained development of
      almost 8 times as many third-stage infective larvae as Cx annulirostris (mean of
      3.8 compared to 0.5), and thus had a vector efficiency index of 57.6 compared to
      1.9 for Cx annulirostris. In a series of investigations Ae.notoscriptus has now
      been shown to be an important vector for dog heartworm in southern Australia and
      may be a significant factor in the apparent burgeoning of the disease.

PMID- 1358268
TI  - Effects of Toxorhynchites moctezuma larval predation on Aedes aegypti
      populations: experimental evaluation.
AB  - Predatory larvae of the mosquito Toxorhynchites moctezuma were used
      experimentally to control a standing crop of larvae of the dengue vector mosquito
      Ae.aegypti. Each week, fifty Ae.aegypti first instar larvae were introduced to
      each of five water-filled drums (220 litres) of the type commonly used for
      domestic water storage in Caribbean dwellings. At the beginning of the fourth
      week, a certain number (0, 1, 2, 5 or 10) of first instar Tx.moctezuma larvae
      were introduced to each drum and the daily yield of Ae.aegypti adults from each
      drum was monitored thereafter. The experiment was repeated three times. With only
      one or two Tx.moctezuma larvae, predation on Ae.aegypti larvae stopped the output
      of Ae.aegypti adults for 1 week. Five or ten Tx.moctezuma prevented any
      Ae.aegypti emergence for up to 16 weeks. Cannibalism among Tx.moctezuma larvae
      was seldom observed and appeared not to be a hindrance in using this species
      against Ae.aegypti. Thus Tx.moctezuma is regarded as a good candidate for the
      biological control of Ae.aegypti by augmentative releases.

PMID- 1358269
TI  - Suppression of Aedes aegypti by predatory Toxorhynchites moctezuma in an island
      habitat.
AB  - Larval populations of the mosquito Aedes aegypti were suppressed by predatory
      Toxorhynchites moctezuma mosquito larvae released systematically in a village on
      Union Island (Saint Vincent and the Grenadines) during March-December 1988. Eggs
      and larvae of Tx.moctezuma were transported from Trinidad and introduced into all
      semi-permanent and permanent water-holding containers in the experimental village
      at Clifton. The semi-isolated village of Ashton served as control. Base-line
      Ae.aegypti indices (house, ovitrap, Breteau, cistern/tank, drum/barrel, small
      containers) were obtained for the two villages over a 4-month period prior to the
      introduction of the predatory Tx.moctezuma mosquito larvae. After sustained
      releases of predators for 5 months, all indices of Ae.aegypti were lower in the
      treated village than in the untreated village during the last 3 months of the
      year.

PMID- 1358270
TI  - Laboratory evaluation of Toxorhynchites splendens (Diptera: Culicidae) for
      predation of Aedes albopictus mosquito larvae.
AB  - Biology of the mosquito Toxorhynchites splendens (Wiedemann) was studied in the
      laboratory to provide baseline data for using the predatory larvae of this
      species against those of Aedes albopictus (Skuse) in a biological control
      programme. The mean incubation time of Tx.splendens eggs was 43.8 h and the time
      required for newly-hatched larvae to initiate predation was 2.5 h. Mean numbers
      of prey larvae consumed and killed by each Tx.splendens larva totalled 389 and
      345 respectively. The larval period of Tx.splendens was not significantly
      different for rearing individually or in groups of nine, with equal prey density,
      and duration of larval development was proportional to prey density. In mass
      rearing, larval cannibalism was usually observed during days 1-3 post-eclosion.
      The incidence of cannibalism decreased sharply on the fourth day after hatching
      when some larvae became fourth-instar. Adult female Tx.splendens usually
      commenced oviposition on day 4 after emergence. The number of eggs laid daily
      increased on day 7 and the peak oviposition of 6.3 eggs/female/day occurred on
      day 11. When oviposition containers were provided only intermittently, gravid
      females of Tx.splendens scattered most of their eggs on the dry floor of the
      cage. Viability of eggs laid by females aged 4-14 days was high (60-90%) but
      decreased to less than 40% as the females aged.

PMID- 1358271
TI  - Biological control of container-breeding mosquitoes, Aedes albopictus and Culex
      quinquefasciatus, in a Japanese island by release of Toxorhynchites splendens
      adults.
AB  - To control container-breeding mosquitoes in the small island of Minnajima (0.56
      km2), northern Okinawa, Japan, laboratory-reared adults (aged 7-10 days) of
      Toxorhynchites splendens (Palawan strain), a mosquito with predatory larvae, were
      released repeatedly during 1984, 1986 and 1987. Thirteen species of mosquitoes
      (Diptera: Culicidae) occurred in artificial containers, ground pools or crab
      holes on the island, the predominant species being Aedes (Stegomyia) albopictus
      and Culex (Culex) quinquefasciatus. Predatory mosquito larvae of Culex (Lutzia)
      fuscanus and Cx (Lt.) halifaxii were found commonly in wet containers. In the
      first year of study, during a period of 54 days from 13 May to 5 July 1984,
      totals of 879 female and 806 male adults of Tx.splendens were released on six
      occasions. Similarly, between 29 April and 30 August 1986, totals of 2920 female
      and 2878 male adult Tx.splendens were released. In the third study year, totals
      of 2041 female and 1783 male Tx.splendens were released on eight occasions during
      199 days from 23 April to 7 November 1987. After adult releases at two sites, the
      immature stages of Tx.splendens were found in 164 out of 502 traps in 1984, 421
      out of 933 traps in 1986, and 151 out of 502 traps in 1987. The number of
      immatures of Tx.splendens present in each trap varied from 1 to 40 in 1984, 1 to
      29 in 1986 and 1 to 9 in 1987. Numbers of immatures of the target species found
      in the traps during August-September averaged 71.9/trap/month in 1984,
      114.7/trap/month in 1986 and 36.0/trap/month in 1987, significantly less in the
      traps with Tx.splendens than in those without them. The present field studies
      indicated that, in this small island, approximately 250 adult female and 200 male
      Tx.splendens per month should be released from April to November, and the
      releases should be carried out every year, in order to control effectively the
      target mosquitoes Ae.albopictus and Cx quinquefasciatus breeding in artificial
      containers in Minnajima.

PMID- 1358272
TI  - Toxorhynchites auranticauda sp.n., a new Indonesian mosquito and potential
      biocontrol agent.

PMID- 1358273
TI  - Talpid2 limb bud mesoderm does not express GHox-8 and has an altered expression
      pattern of GHox-7.
AB  - We have studied the expression patterns of the chick homeobox-containing genes,
      GHox-7 and GHox-8, in the talpid2 (ta2) chick mutant whose limbs have abnormal
      pattern. These studies provide new insight into how homeobox gene expression and
      limb patterning may be related. This is the first study demonstrating a natural
      change in GHox-7 and GHox-8 along the anteroposterior axis. While GHox-7 is
      expressed asymmetrically in normal limb buds, it is expressed at a uniform level
      across the anteroposterior axis of ta2 limb buds. GHox-8 is expressed in anterior
      mesoderm of normal limb buds, but is undetectable in ta2 limb bud mesoderm. These
      data are consistent with the subtle anteroposterior polarity in ta2 limbs, and
      allow us to propose that ta2 limb buds lack anterior positional information, but
      have a narrow range of posterior positional values. We suggest that in normal
      limb buds GHox-8 may establish the anterior limb bud boundary. Furthermore, we
      point out that coexpression of GHox-7 and GHox-8 in normal anterior limb bud
      mesoderm can be correlated with the reduced apical ridge maintenance activity of
      this tissue, while the lack of coexpression in ta2 limb buds is correlated with
      the strong ridge maintenance activity in the mutant's anterior limb bud mesoderm.
      Last, ta2 limbs contain no dying cells in their anterior and posterior border
      mesoderm; nevertheless, they express GHox-7 in these regions. These data
      challenge the proposal that this gene determines cell death.

PMID- 1358274
TI  - Laparoscopic orchiectomy for cryptorchidism.
AB  - A 28-year-old man was admitted for removal of an undescented testis. The
      operation was performed via the laparoscopic approach. Laparoscopy has for years
      been recommended for locating the intraabdominal testis. Therapeutic laparoscopy
      is gaining increased popularity and this brief report shows that an
      intraabdominal testis can be easily removed via the laparoscope.

PMID- 1358275
TI  - The sliding clamp of DNA polymerase III holoenzyme encircles DNA.

PMID- 1358276
TI  - Balloon tamponade and vasoactive drugs in the control of acute variceal
      haemorrhage.
AB  - Successful pharmacological arrest of haemorrhage might avoid the risk of
      aspiration associated with tamponade and early studies have suggested that the
      vasoactive agent somatostatin may be as effective and perhaps safer than
      tamponade in controlling variceal haemorrhage. In our view, vasopressin has not
      established a role in management but we retain an open mind regarding the
      potential use of terlipressin in combination with nitroglycerin. It is unlikely
      that any of these agents can improve significantly our ability to control
      variceal haemorrhage when compared to balloon tamponade but they may reduce the
      incidence of pulmonary complications and thereby reduce subsequent mortality.
      Tamponade has proved successful in controlling acute haemorrhage from oesophageal
      varices in our hands. Late complications continue to give cause for concern but
      until effective safe alternatives to tamponade are developed, we continue to
      advocate its use for emergency control of acute variceal haemorrhage. Our own
      studies have shown that the high mortality seen in this patient population may
      reflect the severity of the underlying liver disease rather than failure of a
      management policy employing oesophageal tamponade for the initial control of
      acute variceal haemorrhage.

PMID- 1358277
TI  - Prophylaxis of first variceal bleeding.
AB  - Surgical, endoscopic and pharmacological treatment options are available for
      prophylaxis of first upper intestinal haemorrhage in cirrhotic patients.
      Randomized controlled trials have revealed that a prophylactic portocaval shunt
      operation should not be performed because its beneficial effect on the bleeding
      rate is outweighed by a slightly increased mortality. Prophylactic portal non
      decompressive surgery (mainly gastro-oesophageal vascular disconnection) has been
      shown to reduce the bleeding rate and mortality in Japanese cirrhotic patients.
      However, further trials in different populations must confirm this positive
      effect. beta-blockers have fewer side-effects and are probably more effective for
      prophylaxis of the first bleed than sclerotherapy, but survival is only
      marginally influenced. Nadolol is preferable to propranolol. The effect of
      sclerotherapy is in part related to the technical experience of the physician.
      Although sclerotherapy has only minor effects on the bleeding rate, it is
      associated with a trend towards a prolonged survival. This may be caused by non
      specific effects. On the basis of the published trials, only preliminary
      recommendations can be given. Prophylactic treatment may be useful in cirrhotic
      patients who are at high risk of bleeding. Life quality may be improved with
      continuous beta-blocker treatment. Some studies suggest that alcoholics with
      large varices may also profit from regular prophylactic sclerotherapy performed
      by experienced physicians.

PMID- 1358278
TI  - Recent developments in the pathophysiology and treatment of hepatic
      encephalopathy.
AB  - The pathophysiology of HE has not yet been clarified. At present the main
      mechanisms under discussion are the combined effects of different toxins, such as
      ammonia, mercaptans, phenols and short- and medium-chain fatty acids, as well as
      a change particularly in GABAergic and glutamatergic neurotransmission. In this
      chapter the current views on the importance of these individual factors in the
      pathophysiology of HE are discussed; possible connections between changes in
      neurotransmission and the effect of different neurotoxins are presented. In
      addition, possible therapies resulting from recent knowledge of the
      pathophysiology of this disease are discussed, such as the use of Bz receptor
      antagonists.

PMID- 1358279
TI  - Effect of histamine H2-receptor antagonists on vitamin B12 absorption.
AB  - OBJECTIVE: To discuss the potential of histamine H2-receptor antagonists (H2RAs)
      to cause malabsorption of vitamin B12 (cyanocobalamin). DATA SOURCES: Pertinent
      literature was identified via a MEDLINE search. Journals and references cited in
      published articles also were used as data sources. STUDY SELECTION: Studies
      evaluating the effect of H2RAs on vitamin B12 absorption were reviewed. DATA
      SYNTHESIS: H2RAs decrease acid secretion by the gastric parietal cells. Gastric
      acid and pepsin produced by these cells are required for the cleavage of vitamin
      B12 from dietary sources. Intrinsic factor (IF), also produced by gastric
      parietal cells, is required for vitamin B12 absorption from the gastrointestinal
      tract. Although H2RAs have not conclusively been shown to decrease IF secretion,
      studies have demonstrated a significant reduction in food-bound vitamin B12
      absorption secondary to decreased acid secretion in patients taking these drugs.
      CONCLUSIONS: H2RAs have the potential to cause vitamin B12 deficiency. This may
      be important in patients with inadequate stores of vitamin B12 (e.g., poor diet),
      particularly those receiving H2RA therapy continuously for more than two years.
      Healthcare providers should be aware of this potential adverse effect.

PMID- 1358280
TI  - Correction: cyanide toxicity from sodium nitroprusside.

PMID- 1358281
TI  - Correction: cyanide toxicity from sodium nitroprusside.

PMID- 1358282
TI  - [12th Forum on Cancer. Paris, 11-13 June 1992. Abstracts].

PMID- 1358283
TI  - Remarkable increase in CD26-positive T cells in patients with human T
      lymphotropic virus type I (HTLV-I) associated myelopathy.
AB  - We used two-color flow cytometric analysis to investigate CD26+ (Ta1+) cells in
      peripheral blood T lymphocytes from patients with human T-lymphotropic virus type
      I (HTLV-I)-associated myelopathy (HAM). The percentage of CD26+ cells among CD3+
      cells was markedly increased in patients with HAM, compared with anti-HTLV-I
      seropositive carriers (p < 0.001) and seronegative controls (p < 0.01). Within
      the subpopulation of T cells, a significantly high percentage of CD26+ cells was
      detected in both CD4+ and CD8+ cell populations. Furthermore, analysis of HLA-DR+
      T cells revealed similar results. In contrast CD4+CD45RA+ cells were
      significantly decreased in comparison with controls. These results suggest that
      immunologically activated or memory T cells found in peripheral blood may be
      etiologically relevant to HAM.

PMID- 1358284
TI  - Localization of phospholipase C-gamma 1 to mouse chromosome 2.

PMID- 1358285
TI  - Localization of the human chromosome 5q genes Gabra-1, Gabrg-2, Il-4, Il-5, and
      Irf-1 on mouse chromosome 11.

PMID- 1358286
TI  - Medium-chain triglycerides and long-term parenteral nutrition in children.
AB  - There are no data concerning long-term utilization of medium-chain triglycerides
      (MCTs) in parenteral nutrition (PN) in children. Our study included 12 children,
      aged 1.5-17 yr, on total PN at home, supplying a daily intake of 214 +/- 92 mg/kg
      nitrogen and 47 +/- 17 kcal/kg nonprotein energy (NPE). NPE included 10-32% long
      chain triglycerides (LCTs) (Intralipid 20%). After switching to emulsion
      containing 50% MCT and 50% LCT (Medialipide) at the same dosage regimen and
      infusion rate as before, the subjects were monitored at 1, 3, and 6 mo. No signs
      of clinical intolerance were observed. Among the laboratory parameters evaluated,
      the only significant (p < 0.05) changes were 1) an increase in apolipoproteins A
      I and A-II at 1, 3, and 6 mo and 2) a decrease in gamma-glutamyltransferase
      (gamma-GT) at 6 mo. There were no changes in the status of essential fatty acids
      in plasma or in phospholipids (in erythrocyte membranes). Moderate urinary
      excretion of dicarboxylic acids (adipic, suberic, and sebacic) was evidence of
      peroxysomal omega-oxidation. The results support the proposal for use of MCT-rich
      emulsion in long-term PN, given its metabolic advantages relative to LCT.

PMID- 1358288
TI  - Proceedings of an International Symposium on Recombinant Factor VIII.

PMID- 1358287
TI  - Chronic ethanol feeding and microvillus membrane glycosylation in normal and
      protein-malnourished rat intestine.
AB  - Ethanol feeding to rats for 40 days enhanced (p < 0.001) the activities of
      alkaline phosphatase, sucrase, gamma-glutamyltransferase (GTP), and p-nitrophenyl
      (PNP)-beta-D-galactosidase (p < 0.05) with no change in leucine amino peptidase
      (LAP) and PNP-beta-D-glucosidase activities in intestine compared with control
      rats. The activities of alkaline phosphatase, sucrase, and GTP were diminished (p
      < 0.01) in ethanol-fed malnourished rats. There was no change in LAP activity,
      but the levels of glucosidase and galactosidase were elevated under these
      conditions. Brush-border sialic acid, fucose, hexose, and hexosamine contents
      were elevated in ethanol-fed protein-deficient animals. Ethanol administration to
      normally fed rats elevated the membrane sialic acid and hexose contents, reduced
      fucose content, and had no effect on brush-border hexosamine content compared
      with the control group. These results are in agreement with data on lectin
      binding to brush borders under these conditions. Alcohol ingestion reduced the
      incorporation of [14C]-glucosamine into brush borders in rats maintained on an
      18% protein diet but augmented the incorporation of [14C]-glucosamine and [14C]
      mannose in protein-malnourished membranes. These observations suggest that
      nutrition status influences the sensitivity of microvillus membrane glycosylation
      to ethanol feeding in rat intestine.

PMID- 1358289
TI  - Postoperative complications and survival after pancreatoduodenectomy in patients
      aged over 70 years.
AB  - An analysis of postoperative complications and survival was conducted in 31
      patients undergoing pancreatoduodenectomy (PD) for carcinoma of the pancreas or
      periampullary carcinoma. Of them, 11 were over 70 years of age and 20 were under
      70. Anastomotic leakage was the most common complication after PD. Definite
      pancreatic leakage was found in one patient in the over 70 group, and one case
      each of pancreatic, biliary, and gastric leakage were found in the under 70
      group. All complications were treated conservatively without any further
      operative intervention. The overall morbidity rate was 41.9% (13/31), being 45.5%
      (5/11) in the over 70 group and 40.0% (8/20) in the under 70 group, and no
      operative deaths occurred within 30 days after surgery. The cumulative survival
      rate of the patients aged over 70 years with carcinoma of the pancreas or
      periampullary carcinoma did not differ significantly from the rate of those under
      70. It was thus concluded that PD achieves an adequate prognosis and survival in
      patients over 70 years of age.

PMID- 1358290
TI  - Gastric emptying after pancreatoduodenectomy with total stomach preservation and
      selective proximal vagotomy.
AB  - This study evaluates postoperative gastric emptying following a new method of
      pancreatoduodenectomy with total stomach preservation and selective proximal
      vagotomy performed on 10 patients with diseases affecting the head of the
      pancreas, 7 being malignant and 3 benign. Reconstruction was carried out using
      the Billroth I and Billroth II techniques in 5 patients each, respectively. Early
      postoperative gastric emptying was evaluated by the time before intragastric tube
      removal and the resumption of oral intake, as well as by barium gastric
      radiography, while late postoperative gastric emptying was evaluated by the
      acetaminophen method. No difference was seen in early postoperative gastric
      emptying between the two surgical techniques, the mean time which elapsed before
      intragastric tube removal being 4.4 days for the Billroth I and 4.5 days for the
      Billroth II patients, and the mean time until the resumption of oral intake being
      6.8 days for the Billroth I and 7.0 days for the Billroth II patients. A
      significant delay in gastric emptying was seen in the Billroth II patients
      compared to a normal control group, 30 and 45 min after acetaminophen
      administration, but the difference in gastric emptying between the Billroth I and
      II patients was not significant. Moreover, both techniques impaired gastric
      emptying much less than Traverso's pylorus-preserving pancreatoduodenectomy.

PMID- 1358291
TI  - What does the preterm infant breathe for? Controversies on apnea of prematurity.

PMID- 1358292
TI  - Persistent Diarrhea in Children of Developing Countries. Proceedings of a
      symposium. Mombasa, Kenya, January 1991.

PMID- 1358294
TI  - [The national symposium on the digestive diseases treated by traditional Chinese
      medicine combined with Western medicine].

PMID- 1358293
TI  - P-glycoprotein-mediated multidrug resistance and cytotoxic effector cells.
AB  - Multidrug resistance (MDR) is one of the major obstacles to successful cancer
      chemotherapy. MDR is a complex and multifactorial phenomenon. One important and
      common mechanism used by cancer cells as a defense against cytotoxic drugs is a
      170-kD plasma membrane glycoprotein, P-glycoprotein (P-gp). P-gp confers
      resistance by actively pumping cytotoxic drugs out of cancer cells.
      Paradoxically, P-gp overexpression on tumor cells is frequently associated with
      enhanced susceptibility to lymphokine-activated killer cell activity. This
      enhanced susceptibility is not observed with P-gp- MDR cells, nor is
      susceptibility to natural killer cells increased. The physiologic, evolutionary
      and immunologic concepts with regard to the P-gp and the possible intervention of
      the function of the P-gp in cancer therapy are reviewed.

PMID- 1358295
TI  - Expression in Escherichia coli of a chemically synthesized gene for the hormone
      somatostatin. 1977.

PMID- 1358297
TI  - The transport of neurotransmitters into synaptic vesicles.
AB  - As investigations identify additional plasma membrane neurotransmitter
      transporters, attention has focused on the molecular basis of neurotransmitter
      transport into synaptic vesicles. The transport of biogenic amines into
      chromaffin granules has served as the paradigm for understanding vesicular
      transport. Recent work now describes the vesicular transport of other classical
      neurotransmitters, which occur by distinct but related mechanisms. To determine
      their biochemical basis, several of the transporters have been functionally
      reconstituted in liposomes. The ability of vesicular amine transport to protect
      against the neurotoxin MPP+ has permitted the isolation of the first cDNA clone
      for a member of this family, and the sequence establishes a relationship with
      drug-resistance transporters in bacteria.

PMID- 1358296
TI  - Intravenous and other novel abuses of benzodiazepines: the opening of Pandora's
      box?

PMID- 1358298
TI  - Retroviruses and nervous system disease.
AB  - During the past decade retroviruses have been recognized as causes of human
      neurological disease. A wide clinical spectrum of neurological and neuromuscular
      diseases have been reported with HIV infections, and studies of these diseases
      have raised novel and exciting hypotheses of pathogenesis. As yet the full
      clinical spectrum of diseases associated with HTLV-1 has yet to be defined, and
      the pathogenesis of the chronic spastic paraparesis remains a mystery. Chronic
      neurological diseases in animals caused by both oncoviruses and lentiviruses can
      provide some clues to the pathogenesis of these newly recognized human
      neurological illnesses.

PMID- 1358301
TI  - The Xp21 myopathies: current research and the prospect for treatment. (20-21
      February 1992, Rome, Italy).

PMID- 1358300
TI  - Neuropsychological performance in asymptomatic HIV infection.
AB  - This study compared 74 human immunodeficiency virus (HIV)-negative and 131 HIV
      positive asymptomatic homosexual or bisexual men on an extensive
      neuropsychological test battery. HIV-positive subjects' performance was
      significantly worse on verbal memory and psychomotor skills. The prevalence of
      mild but persistent neurobehavioral impairment in the HIV-positive group was
      approximately twice that in HIV-negative patients, consistently across several
      criteria for impairment. There was evidence that degree of neuropsychological
      impairment was related to patients' perceptions of dysfunction in daily life.
      Findings were not related to degree of depression or to medication effects. These
      data suggest that approximately 10% to 20% of HIV-positive asymptomatic men
      suffer mild neuropsychological impairment that influences their daily lives.

PMID- 1358299
TI  - N-glycosylation of membrane glycoproteins in retinol-deficient rat liver.
AB  - The effect of vitamin A deficiency on N-linked oligosaccharides of membrane
      glycoproteins was studied in rat liver in order to evaluate the suggested role of
      retinol in protein N-glycosylation. First, oligosaccharides of newly synthesized
      glycoproteins from rough endoplasmic reticulum of vitamin A deficient liver were
      compared with that of pair-fed controls. Oligosaccharides were metabolically
      labelled with D-[2-3H]mannose, released from the glycoproteins with
      endoglycosidase H, purified by reversed phase HPLC and ion exchange
      chromatography, and were reduced with sodium borohydride. HPLC fractionation of
      the oligosaccharide alditols showed that the glycoproteins carried mainly four
      oligosaccharide species, Glc1Man9GlcNAc2, Man9GlcNAc2, Man8GlcNAc2 and
      Man7GlcNAc2, in identical relative amounts in the vitamin A deficient and the
      control tissue. In particular, no increase in the proportion of short chain
      oligosaccharides was noted in vitamin A deficient liver. Second, the number of N
      linked oligosaccharides was estimated in dipeptidylpeptidase IV (DPP IV), a major
      glycoprotein constituent of the hepatic plasma membrane, comparing the newly
      synthesized glycoprotein from rough endoplasmic reticulum and the mature form of
      DPP IV from the plasma membrane. No evidence was obtained that retinol deficiency
      caused incomplete glycosylation of this membrane glycoprotein. From these data,
      the suggested role of retinol as a cofactor involved in the synthesis of N-linked
      oligosaccharides of glycoproteins must be questioned.

PMID- 1358302
TI  - Purification of Rhodotorula gracilis D-amino acid oxidase.
AB  - A protocol is presented for preparing Rhodotorula gracilis D-amino acid oxidase
      in homogeneous form and in high yield in 3 to 4 days. The method takes advantage
      of (a) cell rupture by alternate freeze-thawing, (b) use of DEAE-Sepharose to
      bind contaminants, and (c) enzyme binding to a Mono S column. The D-amino acid
      oxidase isolated by this means has the same spectral and catalytic properties as
      the enzyme previously obtained, and possesses improved long-term stability.

PMID- 1358304
TI  - Analysis of the TSH receptor gene structure in various thyroid disorders: DNA
      from thyroid adenomas can have large insertions or deletions.
AB  - We examined the structure of the TSH receptor gene in various thyroid disorders
      by a restriction fragment length polymorphism (RFLP) study with a cloned human
      TSH receptor cDNA as a probe. Southern blot analysis of DNAs in peripheral white
      blood cells obtained from normal individuals revealed a single band in each of
      several restriction enzyme digestions, indicating that the TSH receptor gene is a
      single copy gene in the human genome. Although RFLPs were not detected in
      peripheral blood cells and thyroid tissues in patients with Graves' disease,
      thyroid carcinomas, or subacute thyroiditis, significant RFLPs were found in 2 of
      6 patients with adenoma in all restriction enzyme digestions examined. Moreover,
      these RFLPs were heterozygous and adenoma specific, and these additional bands in
      adenoma were amplified in both cases. We conclude that there are no major
      abnormalities in the structure of the TSH receptor gene in patients with Graves'
      disease, thyroid carcinoma, or subacute thyroiditis, although there may be a
      possibility of point mutations, small insertions, or deletions that cannot be
      detected by RFLP studies, and that there are large insertions or deletions in the
      region, including the TSH receptor gene, in some patients with thyroid adenoma.

PMID- 1358303
TI  - High-level expression of human asparagine synthetase and production of monoclonal
      antibodies for enzyme purification.
AB  - In order to obtain large quantities of extremely pure human asparagine synthetase
      for detailed kinetic and structural studies, its gene was cloned into a 2mu
      plasmid (pBS24.1GAS) suitable for replication in a Saccharomyces cerevisiae cir0
      strain (AB116). In this construct, the transcription of the asparagine synthetase
      gene is regulated by the alcohol dehydrogenase II/glyceraldehyde-3-phosphate
      dehydrogenase promoter, which is subject to glucose repression. The expression of
      the enzyme was allowed to take place in yeast minimal medium containing D
      galactose as the only sugar nutrient. Eleven monoclonal antibodies to recombinant
      human asparagine synthetase were produced and one of them was selected to make
      immunoaffinity resins. After single-step immunoaffinity chromatography, more than
      1.2 mg of homogeneous enzyme was obtained from the total cell extract from a 100
      ml yeast culture. The yield of pure enzyme was over 100-fold higher than that of
      a previously reported yeast expression system. SDS-PAGE analysis showed the
      enzyme to be extremely pure and isoelectric focusing gel electrophoresis showed
      that the enzyme has an isoelectric point of 7.5. Immunoaffinity-purified
      recombinant human asparagine synthetase demonstrated both glutamine-dependent and
      ammonia-dependent asparagine synthetase activities, as well as glutaminase
      activity.

PMID- 1358305
TI  - The changing health-care system and the new physician.

PMID- 1358306
TI  - Long-term observation of pediatric aplastic anemia.
AB  - Fifty-nine verified cases of acquired aplastic anemia (AA), diagnosed at the
      Pediatric Department of the National Taiwan University Hospital from 1977 to
      1987, were reviewed and analyzed. The demographic features showed a high relative
      incidence (acute myelogenous leukemia/AA ratio, 2.2/1), a high percentage of non
      severe AA (39%) and a high association with hepatitis (20.8%). No evidence of
      hepatitis A, B or C virus infection was found in five cases of hepatitis
      associated AA. No sex preponderance was noted in this pediatric series. The 10
      year projected survival rate of the total series approached 55%. The crude two
      year-survival and two-year-transfusion-free-survival rates were 59% and 44%,
      respectively, in the conservative therapy group treated with androgens and
      steroids; 36% and 32%, respectively, in patients with severe AA in the
      conservative therapy group; and 73% and 64%, respectively, in the aggressive
      therapy group treated with cyclosporin, anti-lymphocyte globulin or bone marrow
      transplant. The major causes of death were hemorrhage (44%) and infection (56%)
      in the conservative therapy group; but in the aggressive therapy group, two out
      of three deaths were related to therapeutic complications. Multivariate analysis
      of prognostic factors revealed that severity and treatment modality were
      independent risk factors. Only two out of 31 patients who survived more than two
      years (long-term survivors) experienced late mortalities. At two, five, seven and
      10 years after diagnosis, 61%, 55%, 41% and 40% of the long-term survivors had
      inadequate hematopoietic recovery.

PMID- 1358307
TI  - Comparison of umbilical blood gas and acid-base status of small-for-date and
      normal Chinese newborns.
AB  - A prospective study of umbilical arterial blood gas in appropriate-for
      gestational-age (AGA) and small-for-gestational-age (SGA) babies was performed at
      our hospital from August 1989 to July 1990. A total of of 512 cases were
      included, 432 cases in the AGA group and 80 cases in the SGA group, with
      gestational ages ranging from 26 to 42 weeks. Umbilical arterial blood was
      collected immediately after delivery of the newborns. Comparisons of maternal
      age, gestational age, birth body weight and body length of infants. Apgar scores
      at one minute and five minutes, cord arterial blood pH, pO2, pCO2, base excess,
      bicarbonate, total CO2, O2 saturation and O2 content between the AGA and SGA
      groups were taken into account. Our results demonstrated significant differences
      in birth body weight, birth body length, Apgar scores at one minute and five
      minutes and gestational age in the SGA group compared with those in the AGA
      group. The parameters of cord arterial blood gas were not correlated with
      gestational age in either group. The mean pH value in the AGA group (7.30 +/-
      0.05) was higher than that in the SGA group (7.28 +/- 0.08). The same trend of
      difference was also noted between the AGA (7.30 +/- 0.04) and SGA (7.27 +/- 0.07)
      babies who were delivered by Cesarean section (p < 0.05). The latter results
      imply a more academic state in SGA babies which is independent of labor.
      Prepartum asphyxia plays an important role in determining the prognosis of SGA
      babies. We suggest routine umbilical cord blood gas and acid-base analysis at
      delivery to assess fetal asphyxia.

PMID- 1358308
TI  - Surgical repair of ventricular septal defect without ventriculotomy in the first
      12 months of life.
AB  - Sixty-eight infants with clinical evidence of a large ventricular septal defect
      (VSD), refractory to conventional medical treatment, underwent surgical closure
      within the first 12 months of life from August 1987 to June 1991. There were 43
      males and 25 females. The ages of the patients ranged from two to 12 months, with
      a mean age of 6.6 months. The mean body weight of the patients was 5.4 kg (range,
      2.3-10 kg). Surgery was performed because of intractable heart failure in 27
      infants (39.7%), failure to thrive in 40 (58.8%), repeated pneumonia in 43
      (63.2%) and prolonged endotracheal intubation in nine (13.2%). There were 21
      patients with a supracristal VSD (30.9%) and 47 patients with perimembranous VSD
      (69.1%). Nine patients (13.2%) had preoperative cardiac catheterization.
      Transatrial repair of perimembranous VSDs and transpulmonary repair of
      supracristal VSDs was used exclusively without ventriculotomy. Surgically induced
      heart blocks did not occur in any of the patients. Only two patients (2.9%) died
      during the early postoperative period. Diagnosis in most cases was confirmed by
      the present advanced integrated color Doppler echocardiographic technology which
      is widely used by pediatric cardiologists. There was no need to perform cardiac
      catheterization in most patients with VSDs. The morbidity and mortality were very
      low. We strongly suggest that for infants with a large VSD, primary repair should
      be the procedure of choice.

PMID- 1358309
TI  - Clinical analysis of 206 cases of kidney transplantation.
AB  - From July 1981 to May 1991, 206 kidney transplantations were performed at the
      Chang Gung Memorial Hospital. There were 762 patients on our waiting list for
      transplantation at that time. Patient follow-up care was undertaken, alternately,
      by urologists and nephrologists. The average follow-up period was 4.0 +/- 2.8
      years. Patient data were registered in the UCLA (University of California at Los
      Angeles) International Kidney Transplant Registry. Eighty patients received
      living-related transplants, 126 received cadaveric transplants. Twenty-four per
      cent of transplant recipients were carriers of HBsAg. Their survival rates were
      equal to those of non-carriers up to five years postoperatively, although they
      were prone to episodes of hepatitis. Nineteen kidneys were from HBsAg carriers
      with recipient survival rates, five years postoperatively, not significantly
      different from those who received kidneys from non-carriers. However, there was
      one case of seroconversion from HBsAg negative to HBsAg positive status. There
      were 19 deaths among the recipients, the major cause of death being infection
      (57.9%). Eight grafts were lost due to medical noncompliance. Malignant lymphomas
      were noted in three cases who are now alive and well. Three cases of hepatomas
      were noted, but unfortunately none of them survived. The transplant recipients
      were found to enjoy a better quality of life after undergoing psychiatric
      evaluation. The one-year patient survival rate was 97.4% and 96.2% for living
      related and cadaveric transplants, respectively. The one-year graft survival rate
      was 96.0% and 88.5% for living-related and cadaveric transplants, respectively.
      Kidney transplantation is a well-accepted method of treatment for end-stage renal
      disease.

PMID- 1358310
TI  - Electroejaculation in spinal cord injured males.
AB  - Electroejaculation is a newly developed method to retrieve sperm in anejaculatory
      spinal cord injured (SCI) males. We studied 25 completely traumatic SCI males
      from August 1990 to May 1991. The patients' ages ranged from 18.7 to 43.3 years,
      and the interval since injury ranged from four months to 14.1 years. The level of
      injury varied from C5 to T12. Bi-directional emission was found in 12 patients,
      antegrade in nine, retrograde in one and failure in three. Electroejaculatory
      stimulation parameters were 434 +/- 54 mA for mean maximum current, 21.7 +/- 2.7
      volts for mean maximum voltage and 35.9 +/- 3.1 degrees C for mean maximum probe
      temperature. The antegrade semen obtained showed wide variations in sperm quality
      and quantity between subjects. The total sperm count was 478 +/- 809 x 10(6) in
      the antegrade portion, and the sperm motility was below 5% in most cases. The
      retrograde portion was usually worse. There was no correlation between sperm
      quality and quantity with patient age, injury level or injury period. Bladder
      management had no effect on the results of electrical stimulation. Epididymitis
      had a negative impact on the success of retrieval. Low-level injury victims
      needed analgesia or anesthesia to complete the stimulation. The major side
      effects were minimal autonomic dysreflexia and mild rectal mucosal change.
      Repeated stimulation may improve sperm counts, but semen quality deteriorates if
      the procedure is performed once a week. As a whole, electroejaculation is a safe,
      effective and simple procedure to retrieve sperm in anejaculatory persons,
      especially SCI patients.

PMID- 1358311
TI  - Measurement of viscosity of human semen with a rotational viscometer.
AB  - The viscosity of 130 human seminal plasma samples was studied with a rotational
      viscometer instead of by the traditional subjective rating method. The average
      seminal viscosity one hour after ejaculation was 9.35 +/- 0.99 centipoise (cps),
      which was statistically identical to that in the third hour (8.63 +/- 0.77 cps).
      Seminal viscosity showed a significant negative correlation with the percentage
      of motile sperm (p < 0.05); however, no significant correlation between seminal
      viscosity and sperm concentration could be found (r = -0.15, p = 0.098). The
      seminal viscosity of the oligoasthenospermic group was significantly higher than
      that of the normospermic group (p < 0.01); there was also a trend towards higher
      viscosity in the semen of asthenospermia and oligospermia when compared with the
      normospermic group. It is concluded that seminal viscosity may be higher in cases
      of poor-quality semen; however, sperm motility and concentration are not the sole
      determinants of viscosity. Determining the seminal viscosity with this rapid,
      objective and quantitative method is valuable in identifying and treating the
      subgroup of infertile men with viscid semen.

PMID- 1358312
TI  - Surgical treatment for Perthes disease at risk.
AB  - The treatment of Perthes disease has remained controversial ever since the
      disorder was first described in 1910. It is generally accepted that surgical
      treatment is favorable if the patients are at risk clinically or radiologically.
      From March 1983 to March 1988, 13 patients suffering from severe Perthes disease
      were treated surgically at the National Taiwan University Hospital. There were 12
      boys and one girl with an average age of eight years and eight months (ranging
      from five years and 10 months to 12 years and one month). They were all at risk
      either clinically or radiologically. All patients suffered from hip pain, limping
      and limited range of motion, except one who was pain-free. All femoral heads were
      classified as Catterall group III or IV, and had at least two radiologic risk
      signs. After nonsurgical treatment for an average duration of 13 months,
      including bed rest, traction and bracing as inpatients or outpatients,
      operations, including varus derotational osteotomy of the femur in three, Salter
      innominate osteotomy in one, combined surgery in three and triple innominate
      osteotomy in six patients, were performed. After following up for 36 months, we
      determined that surgical containment for Perthes disease can achieve satisfactory
      results. In our preliminary report, triple innominate osteotomy was one of the
      relatively simple and effective procedures.

PMID- 1358313
TI  - A dynamic study of the ankle-foot complex.
AB  - A kinematic study of the ankle-foot complex in 19 healthy volunteers was
      performed using computerized radiocinematography. We found that the instant
      centers of rotation of the ankle joint fell closely within the talus in the
      sagittal plane. When the ankle joint moved, the talus, the calcaneus and the
      navicular bone performed different excursions. Except for the movement in the
      sagittal plane, the calcaneus assumed eversion in dorsiflexion and inversion in
      plantar flexion when the ankle moved in an open kinematic chain (under non-weight
      bearing conditions). In a closed kinetic chain movement (under weight-bearing
      conditions), the lower leg exhibited internal rotation, and the talus moved
      plantarward when the ankle was dorsiflexed. The internal rotation of the lower
      leg did not cause a slippery rotation of the foot on the surface, but rather it
      was converted into eversion of the calcaneus in the frontal plane.

PMID- 1358314
TI  - Immunohistochemical study of dystrophin in neuromuscular disorders.
AB  - Dystrophin, a protein product of the gene that is affected in Duchenne/Becker
      muscular dystrophy (DMD/BMD), is localized on the sarcolemma of muscle fibers. We
      tried to study various neuromuscular disorders, including DMD/BMD and their
      carriers, by the immunohistochemical method with two types of anti-dystrophin
      antibodies. No dystrophin stain was found on the muscles of cases of DMD. In
      cases of BMD, partial deficiency or a mosaic appearance of dystrophin was found.
      In members of DMD/BMD families, polyclonal antibody stains did not show definite
      membrane abnormality. However, partial deficiency or a mosaic appearance of
      dystrophin on muscle membranes was found in the carriers by a monoclonal anti C
      terminal antibody stain. The explanation may be: 1) more non-specific antigen
      antibody cross reactions occurred in the polyclonal antibody stain; and 2) a
      partial defect exists, such as a segmental deletion of the C-terminal portion of
      dystrophin. Dystrophin study in muscle diseases is a helpful tool for the
      following reasons: 1) it improves diagnostic accuracy and helps to differentiate
      variant types of muscle disorders; 2) it makes an early diagnosis possible before
      the onset of the symptoms of DMD/BMD; and 3) it detects nonsymptomatic carriers
      of DMD/BMD. However, without the aid of a genetic study, dystrophin antibody
      stains cannot absolutely rule out the diagnosis of carriers.

PMID- 1358315
TI  - Tubal embryo transfer for the treatment of infertility.
AB  - The outcome of treatment for male factor infertility with either gamete
      intrafallopian transfer (GIFT) or in vitro fertilization and embryo transfer
      (IVF/ET) has been unsatisfactory. A better approach may be tubal embryo transfer
      (TET). In our medical center, from November 1989 to December 1990, 80 couples
      (male factor, n = 35, non-male factor, n = 45) entered our program for TET.
      Superovulation was conducted with either human menopausal gonadotropins (hMG) or
      gonadotropin-releasing hormone agonist (GnRH-a, buserelin)/hMG. Ovum retrieval
      (OR) was possible in 73 patients and successful fertilization after insemination
      occurred in 64 of them. TET was performed only when there was at least one grade
      III-V embryo. The mean number of embryos transferred was 3.92 +/- 0.13 (range 1
      5). There were 35 pregnancies out of 55 TET (64% per TET, 48% per OR). In the
      group with male factor infertility, OR occurred in 32, and 24 achieved
      fertilization. Ten pregnancies were achieved after 19 TET (53% per TET, 31% per
      OR). In comparison, the group with non-male factor infertility had a higher
      pregnancy rate (69% per TET and 61% per OR). There have been 15 live births, 14
      ongoing pregnancies (eight sets of twins and 21 singletons), five abortions and
      one ectopic pregnancy. Our results indicate that: 1) TET is a valuable treatment
      for non-tubal factor infertility; and 2) in the group with male factor
      infertility, it has the advantages of demonstrating fertilization in vitro and
      preventing unrewarding laparoscopies.

PMID- 1358316
TI  - Experience with treatment of gastroschisis and omphalocele.
AB  - From 1982 to 1990, 31 neonates with omphalocele and 54 with gastroschisis were
      treated at Mackay Memorial Hospital. The overall survival rate for omphalocele
      was 71%, while it was 85% for gastroschisis. The rate of primary fascial closure
      for omphalocele (85%) and gastroschisis (87%) was similar. The mortality from
      omphalocele was almost exclusively due to the presence of serious associated
      congenital anomalies. Two cases of Cantrell's pentalogy and two of cloacal
      exstrophy were found. The incidence of major malformation with gastroschisis was
      6%. Sepsis, inadequate perioperative resuscitation and prolonged gastrointestinal
      dysfunction were the major causes of death in gastroschisis. Among survivors, the
      hospital stay was significantly longer in the silon pouch group than in the
      primary fascial closure group (71.5 vs 31.3 days for gastroschisis, 41 vs 14 days
      for omphalocele). Advances in surgical technique, neonatal intensive care and
      ventilatory support have made primary fascial closure a superior approach without
      jeopardizing the babies' chance for survival. An improved survival rate and
      increased primary closure rate are the main features in the treatment of
      abdominal wall defects in the last decade.

PMID- 1358317
TI  - Effects of age and posture on plasma active renin and plasma inactive renin in
      normal subjects.
AB  - To investigate the effects of age and posture on plasma active and inactive
      renin, we measured the plasma active renin concentration (ARC) and inactive renin
      concentration (IRC) in 81 healthy subjects. The subjects were divided into five
      groups according to age and body position at the time the blood was taken. Group
      I included 15 five-day-old newborns in a supine position. Group H included 18
      adults, aged from 20 to 50 years, who were in a supine position. Group III
      included 21 adults, over 50 years old, who were in a supine position. Group IV
      included 20 adults, aged from 20 to 50 years, who were in an upright position.
      Group V included 19 adults, over 50 years old, who were in an upright position.
      Twelve subjects were included in Groups II and IV. Plasma active renin was
      measured by the amount of angiotensin I general when an exogenous renin substrate
      was added. Plasma inactive renin was activated by trypsin. The results showed
      that, in a supine position, both ARC and IRC were significantly higher in
      newborns (Group I) than in the two adult groups (Groups II and III). The mean of
      the ARC/TPRC (total plasma renin concentration) ratio was lower in adults over 50
      years old (Group III) than in those from 20 to 50 years old (Group II), but the
      difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358318
TI  - Metastasis of hepatocellular carcinoma to the heart: unusual patterns in three
      cases with antemortem diagnosis.
AB  - Unusual patterns of cardiac metastasis were noted in three cases of
      hepatocellular carcinoma (HCC): one patient was noted to have a large right
      ventricular (RV) tumor mass with intracavitary growth and myocardial invasion;
      the second had massive pulmonary and left atrial (LA) metastasis; and the third
      patient had a right atrial tumor mass with concomitant RV and LA involvement.
      Tumor implantation to the RV without right atrial involvement and extensive
      myocardial invasion is unusual in HCC. The LA involvement is probably related to
      tumor growth from the pulmonary veins following massive metastasis to the lung,
      direct invasion of the atrial septum or tumor implantation via a subclinical
      right-to-left shunt through the patent foramen ovale. To the best of our
      knowledge, such unusual intracavitary metastases in HCC have not been reported
      previously. Cardiac metastasis, without local gross recurrence, may be one of the
      presentations after lobectomy in patients with HCC.

PMID- 1358319
TI  - Cutaneous alternariosis in association with scabies or iatrogenic Cushing's
      syndrome.
AB  - Cutaneous alternariosis is rare. Most infections occur in immunocompromised
      hosts. We report the first three cases in Taiwan. The patients were elderly
      farmers residing in Tainan. They developed indolent, erythematous, ulcerated or
      crusted papules, plaques or pustules over the extensor aspect of the forearms or
      hands. Pure colonies of Alternaria sp were isolated from biopsy specimens in each
      case. The diagnosis was confirmed by detecting pleomorphic fungal elements in the
      dermis within suppurative, granulomatous infiltrates. All three patients were
      immunocompromised. They showed a negative reaction to an intradermal test of
      seven common antigens. Cases 2 and 3 had iatrogenic Cushing's syndrome. Cases 1
      and 3 had extensive scabies, which in Case 1 was of the Norwegian type. To the
      best of our knowledge, scabies associated with alternariosis has not been
      reported previously. The infection showed spontaneous regression in Case 1; in
      Case 2, it resolved after seven weeks of intralesional amphotericin B at a dose
      of 1 mg/mL twice a week.

PMID- 1358320
TI  - Computed tomographic finding in adenomyomatosis of the gallbladder.
AB  - We report on an uncommon case of symptomatic generalized adenomyomatosis of the
      gallbladder. It was initially suspected by ultrasonography and further confirmed
      by computed tomography (CT). A postcontrast CT scan at the level of the
      gallbladder body demonstrated the characteristic rosary sign. The rosary sign is
      formed by the enhanced proliferative mucosal epithelium with the intramural
      diverticula surrounded by the unenhanced hypertrophied muscle coat of the
      gallbladder. Similar CT scans were obtained sequentially in the caudal direction.
      These CT scan findings indicated generalized adenomyomatosis of the gallbladder.
      The patient received a cholecystectomy. The pathologic report showed specific
      changes of adenomyomatosis corresponding to the findings on the CT scan.
      Generalized adenomyomatosis of the gallbladder, therefore, can be accurately
      diagnosed by CT.

PMID- 1358321
TI  - Congenital short bowel syndrome: report of a case treated with home central
      parenteral nutrition.
AB  - Congenital short bowel is a rare anomaly. Among the 21 cases reviewed in the
      literature, only four (19%) survived beyond infancy. We present a female infant
      with short small bowel, malrotation and floating colon, who was successfully
      treated with home central parenteral nutrition. Improved long-term survival in
      this group of patients is expected with prolonged parenteral nutritional support.

PMID- 1358322
TI  - Pericentric inversions of chromosome 9 in Taiwanese fetuses.
AB  - Using trypsin-Giemsa banding, a total of 1,350 unrelated Chinese fetuses were
      studied for pericentric inversion of chromosome 9 [inv(9) (p11; q13)]. Sixteen
      cases (1.2%) were found to have this variant. The prevalence was higher than that
      in a previous report on Asians. All the fetuses with inv(9) were born with a
      normal phenotype.

PMID- 1358324
TI  - PCR amplified HLA DQ alpha and DQ beta DNA typed by dot-blot hybridization and
      direct sequence for suspect.
AB  - For more effective screening of suspects, we combined two methods to
      individualize the biologic evidence from a crime scene: polymerase chain reaction
      (PCR) dot-blot hybridization for DNA typing of HLA Dq alpha; and PCR direct
      sequencing for DNA typing of HLA DQ beta. PCR-DQ alpha was typed by an AmpliType
      HLA DQ alpha kit from Cetus. PCR-DQ beta was typed by direct sequence using the
      dideoxy chain termination method. In 20 DNA samples, complete separation was
      demonstrated by these two polymorphic DNAs. This will be of considerable use in
      screening suspects in crime investigation work. The sensitivity of PCR is useful
      for trace evidence, and the rapid results of dot-blot hybridization and the
      precise results of direct sequencing have significant advantages.

PMID- 1358325
TI  - Effects of splenectomy on portal pressure in short- and long-term portal
      hypertensive rats.
AB  - Different hemodynamic patterns were noted in short- and long-term portal
      hypertensive rats, induced by partial portal vein ligation (PVL) performed two
      weeks and six months earlier. In order to investigate the effect of splenectomy
      on the portal pressure of portal hypertensive rats with different hemodynamics,
      an operation was performed on these two groups of animals and the portal pressure
      measured thereafter at different time points. Splenectomy in the short-term group
      produced an immediate, but transient, drop in portal pressure from 14.1 +/- 2.7
      to 11.0 +/- 3.0 mmHg, which bounced back to pre-splenectomy values in 20 seconds.
      Two weeks later, the portal pressure in these splenectomized rats was 15.2 +/-
      4.2 mmHg, which was indistinguishable from that of the pre-splenectomy condition
      of the short-term group. However, after an additional two weeks, portal pressure
      in the splenectomized rats rose to 16.4 +/- 2.1 mmHg, which was significantly
      higher than that of the pre-splenectomy condition of the short-term group. This
      difference in portal pressure became even more pronounced at six months.
      Sustained portal hypertension was observed in the long-term group, but the
      pressure was significantly lower than that in the short-term group. Splenectomy
      in the long-term group produced neither an immediate drop nor a delayed rebound
      in portal pressure. We conclude that splenectomies in portal hypertensive rats at
      different stages of disease produce different effects.

PMID- 1358326
TI  - C-peptide response to glucagon in patients with non-insulin-dependent diabetes
      mellitus.
AB  - To understand pancreatic beta cell function in patients with non-insulin
      dependent diabetes, we analyzed C-peptide response to glucagon in 101 nonketotic
      patients with onset of diabetes at over 25 years of age and duration of diabetes
      of more than one year. The fasting serum C-peptide values (FCP), maximal
      incremental (delta CP) and 6-minute (6'CP) serum C-peptide values after 1 mg of
      intravenous glucagon administration were not related to age at diagnosis (r =
      0.12, 0.06 and 0.10, respectively), duration of diabetes (r = 0.15, 0.05 and
      0.10, respectively), fasting plasma glucose concentrations (r = 0.01, 0.18 and
      0.12, respectively) or glycohemoglobin (HbA1c, r = 0.13, 0.22 and 0.16,
      respectively). In contrast, they showed a clear positive correlation with body
      mass index (BMI, r = 0.36, 0.52 and 0.41, p < 0.001). In order to evaluate the
      beta cell function in patients with different responses to treatment modalities,
      a subgroup of 45 patients was divided into three groups: diet successes (DS, n =
      14), oral hypoglycemic agent (OHA) successes (OS, n = 19) and OHA failure (OF, n
      = 12). Among the three groups, patients in the OF group had the longest duration
      of diabetes (9.4 +/- 1.9 years) and the lowest BMI (19.3 +/- 1.0 kg/m2). Serum C
      peptide responses to glucagon were different in the three study groups. Patients
      in the DS group had the highest response and patients in the OF group had the
      lowest response. However, the differences in mean FCP, delta CP and 6'CP among
      the three groups were not statistically significant, and there was a wide overlap
      of individual C-peptide values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358323
TI  - Acute renal failure and severe thrombocytopenia induced by rifampicin: report of
      a case.
AB  - We report on a patient who developed life-threatening thrombocytopenia and acute
      renal failure after the reinstitution of rifampicin therapy for pulmonary
      tuberculosis. This combined reaction is rarely reported. Supportive treatment and
      withdrawal of rifampicin led to complete recovery. The increased incidence of
      drug-resistant tuberculosis and the need for the reintroduction of rifampicin
      therapy may lead to more such reactions being observed.

PMID- 1358327
TI  - Treatment and outcome of unexplained recurrent spontaneous abortions in
      subclinical autoimmune disorders.
AB  - Patients with a history of three or more fetal losses before a gestational age of
      20 weeks were examined. Only patients with normal chromosomal, hormonal and
      anatomic findings were included in this study. These patients were tested for the
      antinuclear antibody, the C3 and C4 levels, anti-ENA [Ro(SSA), La(SSB), SM, RNP,
      scl-70], anti-single-stranded DNA and anti-double-stranded DNA, lupus
      anticoagulant, anticardiolipin and antiphosphotidylserine. All of these patients
      were free of any symptoms, except for the repeated abortions. The results showed
      that 10 out of 213 (4.7%) patients with unexplained recurrent spontaneous
      abortions had abnormal serologic tests, and 28% of the abortions (nine out of 32
      abortions) occurred during the second trimester. With treatment of low-dose
      aspirin alone, or in combination with prednisolone, two out of 11 pregnancies in
      these 10 patients resulted in repeated abortions (18%), which was significantly
      lower than their previous abortion rate where 32 out of 33 pregnancies resulted
      in abortions (97%). Four babies (three term and one premature) were delivered
      without any abnormalities and the other five pregnancies are beyond the 28th week
      of gestation and are progressing smoothly. This study revealed that subclinical
      autoimmune disorders may play a role in recurrent spontaneous abortions and
      adequate treatment can improve the pregnancy outcome.

PMID- 1358328
TI  - Wilson's disease: clinical analysis of 71 cases and comparison with previous
      Chinese series.
AB  - We analyzed 71 patients (45 males and 26 females) with Wilson's disease (WD) who
      were seen at our hospital from 1979 through 1990. The mean age at onset was 18.1
      +/- 6.5 years, with 17.0 +/- 6.6 years for males and 20.2 +/- 5.7 years for
      females. The mean age at the time of diagnosis was 21.0 +/- 6.3 years. Hepatic WD
      was the most frequent mode of presentation in childhood with a mean age of 15.5
      +/- 6.0 years, while neurologic WD tended to occur in adolescence with a mean age
      of 21.0 +/- 8.9 years. The ages of onset were 12.5 +/- 0.5 years for renal WD and
      25.3 +/- 2.4 years for psychiatric WD. The common initial symptoms were
      neurologic and hepatobiliary. In addition, hematologic and renal disorders were
      also common during evaluation. The neurologic findings at the time of diagnosis
      were tremors (66.2%), dysarthria (56.3%), gait disturbances (46.5%), dystonia
      (42.3%) and decreased facial expressions (40.8%). Less frequent but notable
      neurologic presentations were psychosis (11.3%), epileptic seizures (5.6%) and
      hypokalemic periodic paralysis (1.4%). When compared with two previous large
      Chinese series, the present data show a male preponderance, an earlier age of
      onset for males and higher incidences of hepatic, hematologic and renal
      involvement. The possible reasons for the discrepancies between the present study
      and previous Chinese series are discussed.

PMID- 1358329
TI  - Dorsal root entry zone lesions in the treatment of pain following brachial plexus
      avulsion and herpes zoster.
AB  - Fifteen patients with brachial plexus avulsion injury and four patients with
      postherpetic pain submitted to dorsal root entry zone surgery. Nashold's method
      was used in all cases. The initial results in the group with brachial plexus
      avulsion injury were satisfactory. Twelve patients experienced pain relief. Only
      one patient had a poor result. Ten patients (66%) continued to have good pain
      relief in the follow-up period of 15-48 months. Three patients with postherpetic
      pain had good pain relief in the initial stage after surgery. Two of these four
      cases were found to have a recurrence of some pain, which could be relieved more
      or less by oral analgesics. No mortality or major complications were found in
      this series, although eight patients complained postoperatively of mild sensory
      weakness which disappeared within two weeks.

PMID- 1358330
TI  - Can cancer pain attenuate the physical dependence on chronic long-term morphine
      treatment?
AB  - This prospective and comparative study was designed to determine the role of
      cancer pain and attitudes towards morphine in attenuating the intensity and
      duration of physical dependence following chronic morphine treatment. Morphine
      was administered via a stepwise ladder approach in order of oral, spinal and
      intravenous routes depending on the adequacy of analgesia. On-demand titration of
      a dose, either upward or downward, was liberal and unlimited. Withdrawal strategy
      was evaluated and initiated either by patients (PI group) or their families (FI
      group). The manifestation of physical dependence on morphine was compared between
      patients who successfully withdrew (total withdrawal), and patients who failed to
      withdraw (episodic withdrawal), from morphine for a period of more than two
      weeks. Eighty-eight out of 627 patients (14.1%) were excluded from our protocol;
      75% of these exclusions were due to objections toward morphine as the major form
      of analgesic. Drop-out due to poorly tolerated side effects was relatively rare
      (18.2%). Fifty-four (10.0%) achieved total withdrawal and 212 (39.3%) experienced
      episodic withdrawal. Non-pain-related abstinence symptoms were highly prevalent
      but were tolerable for both groups. Pain-related symptoms were more exaggerated
      during episodic withdrawal. Intolerable pain, rather than physical dependence,
      contributed to the failure to withdraw from morphine. Among a total of 539,
      addiction was found in only one patient (0.18%) who began drug use long before
      entering our protocol. Attitudes towards morphine affect the acceptance of
      treatment and hasten the withdrawal strategy. Families were more anxious about
      morphine than the patients themselves which led to more aggressive, but less
      tolerable, withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358331
TI  - Conization with a carbon dioxide laser as a uterine-preservation operation for
      patients with preinvasive cervical carcinoma.
AB  - Preinvasive cervical carcinoma (PCC) is a disease entity of the uterine cervix
      resulting from carcinoma in situ and various degrees of dysplasia. These cases
      are conventionally treated by a total abdominal hysterectomy. Effective
      management that can preserve the uterus is more desirable than hysterectomy. In
      this report, we present the results and complications of laser conization as a
      uterine-preservation treatment. At our dysplasia clinic, cases of reproductive
      age diagnosed with PCC can voluntarily undergo laser conization. From June 1985
      to May 1988, there were 26 cases who received this treatment. After treatment,
      they were regularly followed up for more than three years. Before and after
      surgery, these cases were evaluated by a Pap smear for cytology, colposcopy, a
      cervical punch biopsy and endocervical curettage for histopathology. Eighteen
      cases with a satisfactory colposcopy were treated by laser vaporizing conization.
      Eight cases with an unsatisfactory colposcopy were treated by laser excisional
      conization. Their mean age was 35.8 (SD 7.7) years, and parity was 1.5 (SD 0.9).
      The instrument used was a Sharplan CO2 laser model 720. The power density was
      around 1,000 W/cm2 for vaporization, and 1,500 W/cm2 for excisional conization.
      During the operations, there was little bleeding. No case required a blood
      transfusion. The vaginal discharge decreased within four days after treatment.
      The cervical epithelium on the operated wound began growing after the second
      week, and the cervix healed well in four to six weeks. After healing, the
      squamocolumnar junction in each case was visible on colposcopy. No case suffered
      from cervical stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358332
TI  - Secondary ovarian malignancy of extragenital origin: clinical analysis of 42
      cases.
AB  - Forty-two patients with secondary ovarian cancer from extragenital sites
      encountered in the past 14 years at the National Taiwan University Hospital were
      retrospectively analyzed. They accounted for 11.6% (42/362) of all ovarian
      cancers. The mean age was 43.7 years, and 32 patients were premenopausal. Gastric
      cancer was the most frequent primary malignancy (50.0%); other sites of
      extragenital primaries were colon (23.8%), breast (11.9%), rectum (4.8%), and
      indeterminate (9.5%). Bilateral ovarian involvement was found in 78.6% of
      patients. The most common presenting symptom was abdominal distension (52%). All
      patients received surgical intervention as the primary treatment; 30 patients had
      subsequent chemotherapy and four patients had postoperative radiotherapy.
      However, the outcome was poor; more than half of the patients died within one
      year, with a two-year survival rate of 22.5%.

PMID- 1358334
TI  - Computed tomography in diagnosis of septic sacroiliitis: report of three cases.
AB  - Disorders of the sacroiliac joint are often overlooked during an initial physical
      examination because the patient is usually in a supine position and the
      posteriorly located joint is not accessible. Local pain and tenderness at the
      sacroiliac joint on lateral compression of the pelvis, together with Gaenslen and
      Fabere maneuvers, may direct the physician's attention to the joint. However,
      these symptoms are not specific or pathognomonic. Unusual presentation of septic
      sacroiliitis, which does not show radiologic changes during the early stages, may
      mimic gluteal, lumbar disc or intra-abdominal syndromes, leading to unnecessary
      abdominal exploration or lumbar discectomy. Computed tomography (CT), with its
      superb delineation of osseous, synovial and peri-articular structures, was
      applied to diagnose septic sacroiliitis in three patients. In Patient 1, septic
      arthritis and juxta-articular osteomyelitis with sequestrum formation were
      demonstrated by CT four weeks before abnormalities were shown on a roentgenogram.
      In Patients 2 and 3, inflammatory processes affected the synovium and peri
      articular muscles; thus, abnormalities were shown by CT but not by a
      roentgenogram. We consider CT to be helpful and superior to conventional
      radiography in the diagnosis of septic sacroiliitis.

PMID- 1358333
TI  - Management of infected tibial plate osteosynthesis using a staging system for
      infected fractures.
AB  - Osteomyelitis following plate osteosynthesis of a tibial shaft fracture was
      managed in 23 patients through a staging system and prospective treatment
      protocol. The staging system, which is arranged in an upstaging disease
      progression and downstaging treatment protocol, is composed of the status of
      osseous continuity (Type I to II) and the dead space created by the debridement
      surgery (Classes A to D). The follow-up period ranged from 20 to 48 months
      (average, 31.5 months). Staphylococcus aureus (35.5%) and Pseudomonas aeruginosa
      (29%) were the most commonly involved organisms. Twenty-two infections were
      initially arrested by one debridement, and one infection was arrested by three
      sequential debridements. There were seven Stage IA, one Stage IB, seven Stage
      IIA, two Stage IIB, three Stage IIC, and three Stage IID fractures in this study.
      The average number of surgical procedures were 1, 2, 2.1, 4, 4.7 and 6,
      respectively. The difficulty of treatment increased with the severity of the
      disease. The average time to bone union for Stage IIA, IIB, IIC and IID fractures
      were 11, 9, 20.3 and 21.5 months, respectively. A tibial osseous defect longer
      than 4 cm is a major prognostic factor for prolonged disability time. Important
      complications were nonunion one, bone graft stress fractures (two), and
      recurrence (three).

PMID- 1358335
TI  - Non-mosaic trisomy 20 in cultures of amniotic fluid from a fetus with serious
      congenital malformation.
AB  - We present a case of non-mosaic trisomy 20 in amniotic fluid associated with
      major congenital anomalies. A detailed prenatal ultrasonic examination was
      performed, and revealed dilatation of the cisterna magna and the fourth ventricle
      with hypoplasia of the vermis of the cerebellum. Fetal echocardiography showed
      overriding aorta and ventricular septal defects with pulmonary atresia. However,
      the karyotype of the lymphocyte in the cord blood was normal female 46, XX. The
      occurrence of the Dandy-Walker malformation in non-mosaic trisomy 20 has not been
      reported before, and the clinical significance of this major defect for prenatal
      diagnosis is discussed.

PMID- 1358336
TI  - Incomplete prepenile scrotum: report of two cases and review of literature.
AB  - An incomplete prepenile scrotum is an unusual anomaly. Two cases of incomplete
      prepenile scrotum are presented here, both of which are associated with a small
      phallus, hypospadias and a bifid scrotum. No sex chromosome disorder or
      hereditary factors contribute to such a disorder. Early surgical correction is
      recommended.

PMID- 1358337
TI  - Treatment of symptomatic syringomyelia with ventriculoperitoneal shunt: report of
      a case.
AB  - We report on a 43-year-old female who, for 27 years, had thoracic scoliosis with
      curve convexity to the left side. She complained of rapid progression of the
      central cord syndrome in the past two years. Magnetic resonance imaging (MRI)
      demonstrated a syringomyelia with a direct connection between the fourth
      ventricle and the syrinx. The patient underwent a ventriculoperitoneal shunt and
      showed rapid neurologic improvement. A follow-up MRI showed dramatic shrinkage of
      the syrinx.

PMID- 1358338
TI  - Primary medullary hemorrhage: report of a case.
AB  - A 40-year-old normotensive man suddenly developed dizziness, vomiting, hoarseness
      and swallowing disturbance. Neurologic examinations showed bilaterally decreased
      palatal elevation and gag reflex, upbeat nystagmus and gait ataxia. The diagnosis
      of medullary hemorrhage was first established by computed tomography (CT).
      Magnetic resonance imaging study further showed a hematoma in the paramedial
      medulla oblongata extending dorsorostrally to the pontomedullary junction. It
      gave the precise anatomic boundary of the intramedullary hematoma and was well
      correlated with the clinical findings. This patient's subsequent prognosis was
      good with gradual improvement of the clinical signs and symptoms. A follow-up CT
      scan showed resolution of the hematoma, and the prognosis was consistent with a
      good neurologic recovery.

PMID- 1358339
TI  - A simple and effective method of compression dressing for skin grafts.
AB  - Skin grafting is one of the most common procedures in plastic and reconstructive
      surgery. Various methods of fixation and dressing, to achieve good approximation
      and immobilization of skin grafts and, thus, to bring about better graft
      survival, are described. A simple method utilizing readily available latex and
      staples provides good fixation and compression. This technique has been applied
      in 50 patients requiring skin grafts. The morbidity and complications were
      minimal, and the grafts have taken satisfactorily. Pressure study with an animal
      model has revealed adequate compression.

PMID- 1358340
TI  - Detection of enterovirus RNA in patients with idiopathic dilated cardiomyopathy
      by polymerase chain reaction.
AB  - The pathogenic role of enterovirus in patients with idiopathic dilated
      cardiomyopathy has been determined through a molecular biologic approach.
      Sensitivity in the detection of viral genomes in tissues varied between
      conventional nucleic acid hybridization and polymerase chain gene amplification.
      To improve diagnosis, we developed a strategy for reverse transcription
      polymerase chain reaction (RT-PCR) to detect viral RNA. We synthesized two
      sequence-specific oligonucleotides, primer 1 (5'dACCGACGAATACCACTGTTA3') and
      primer 2 (5'dCCTCCGGCCCCTGAATGCGGCTAAT3'), complementary to the 5' conserved
      viral genomic fragments. Viral RNA was amplified by double PCR with these two
      primers and hybridized with a 32-P labeled inter-primer probe
      (5'dATGAAACCCACAGGCACAAAG3'). Using this strategy, we detected as little as 10(
      8) micrograms of coxsackievirus B3 RNA after amplification with RT-PCR, but
      detected none in the plasma of eight healthy adults. Among 15 patients with
      idiopathic dilated cardiomyopathy, viral RNA could be detected in one out of 12
      plasmas (8%) and three out of four explanted heart tissues (75%). In contrast, no
      viral RNA could be detected in six samples of myocardial tissue from patients
      with other heart diseases. The only patient who had viral RNA in his plasma also
      had viral RNA in his myocardium. Thus, the high incidence of viral RNA in these
      patients suggests a possible etiologic link between them. Correct selection of
      specific PCR primers and the application of double PCR can improve chances of
      diagnosing enteroviral infection.

PMID- 1358341
TI  - Comparison between carotid duplex sonography and angiography in the diagnosis of
      extracranial internal carotid artery occlusion.
AB  - To determine the diagnostic accuracy of extracranial internal carotid artery
      (ICA) occlusion by carotid duplex sonography and ophthalmic flow direction, we
      compared both carotid sonograms and angiograms in 82 cases of ischemic
      cerebrovascular disease. A total of 157 carotid arteries were available for
      comparison. The overall diagnostic accuracy of ICA occlusion by duplex scanning
      was 96% (sensitivity, 83%; specificity, 98%; positive predictive value, 91%), by
      ophthalmic flow examination, 95% (sensitivity, 79%; specificity, 98%; positive
      predictive value 86%), and by combined study, 98% (sensitivity, 96%; specificity,
      98%; positive predictive value 92%). We recommend that the ophthalmic flow
      examination should be used in combination with other sonographic methods in
      detecting extracranial carotid artery disease. The combined study gives higher
      diagnostic accuracy than the single method. When an occlusion or a tight stenosis
      is uncertain on carotid sonograms, color Doppler or angiography is indicated for
      further confirmation.

PMID- 1358342
TI  - The simultaneous use of electrocochleogram, brainstem auditory evoked potential
      and facial muscle EMG in cerebellopontine angle tumor removal.
AB  - In six cases of acoustic neurilemmoma, electrocochleogram (ECOchG), brainstem
      auditory evoked potentials (BAEP) and facial muscle electromyograms (EMG) were
      recorded to monitor facial nerve and brainstem function. Under isoflurane and
      nitrous oxide anesthesia, we recorded ECOchG from the tympanic membrane, BAEP
      from the scalp needle, and facial muscle EMG from the mentalis muscle. During
      surgery, the body temperature was kept above 36.5 degrees C, and PaCO2 above 30
      mmHg. In all cases, the peak N1 of ECOchG and wave I of BAEP had identical
      latencies throughout the monitoring period. The response was faster and the
      amplitude was higher in the ECOchG recordings. For calculation of the I-III or I
      V interpeak latency of BAEP, the wave I of BAEP could be confirmed more quickly
      and precisely by the peak N1 of ECOchG. During tumor removal, the embedded facial
      nerve pathway in the tumor was identified by electric stimulation of the
      intracranial facial nerve, followed by evoked facial muscle EMG. Facial nerve
      function was confirmed by nerve traction or direct electric stimulation after
      total removal of the tumor. No facial palsy or other neurologic sequelae was
      found after the operations.

PMID- 1358343
TI  - Delayed traumatic intracerebral hemorrhage: a study of prognostic factors.
AB  - Experience in the management of 32 patients with delayed traumatic intracerebral
      hemorrhage (DTICH) is presented with emphasis on the incidence, clinical
      significance and factors affecting the outcome. The incidence was 1.4% of all
      hospitalized head-injury patients, or 5.9% of only those patients with neurologic
      signs or abnormal findings on computed tomography (CT) identified on admission.
      After an injury, every patient had an immediate CT scan to diagnose intracranial
      pathology. Initially, nine patients underwent a craniotomy for intracranial
      hematomas, and 23 patients had nonoperative treatment. CT follow-up was carried
      out in 10 patients due to clinical deterioration and on 22 patients due to
      failure to recover neurologically. The delayed hemorrhage was found after a time
      interval varying from seven hours to 10 days (average, three days and seven
      hours). Six patients underwent operations for DTICH, and 26 were treated
      conservatively. Twenty-four patients (75%) were functional (good or moderately
      disabled condition) after one year of follow-up treatment, as measured on the
      Glasgow Outcome Scale. The mortality was 16%. The patients were predicted to have
      a poor prognosis if associated with an earlier occurrence, the hematoma was
      large, the patient had a poor Glasgow Coma Scale score at the time of CT follow
      up, clinical deterioration was noted, or partial or complete effacement of the
      suprachiasmatic cistern was noted on the CT scan. The results indicate that the
      prognosis of DTICH is not as poor as it was previously thought to be, and the
      factors affecting the outcome in this study seem to justify a more vigilant
      approach.

PMID- 1358344
TI  - Apolipoprotein levels in normolipidemic non-insulin-dependent diabetes mellitus.
AB  - The purpose of this study was to examine the change in apolipoprotein and
      lipoprotein levels in patients with normolipidemic untreated non-insulin
      dependent diabetes mellitus (NIDDM). Fifteen untreated, non-obese male NIDDM
      patients without hyperlipidemia were chosen, and 15 healthy subjects, matched for
      age, sex, body weight, alcohol consumption and cigarette smoking served as the
      control group. We observed that the concentrations of plasma total cholesterol
      (TC), triacylglycerol (TG) and very low density lipoprotein cholesterol (VLDL-C)
      were identical in both NIDDM and control groups. The levels of low-density
      lipoprotein cholesterol (LDL-C) were slightly increased in the diabetic group,
      but the difference did not reach statistical significance in our study. High
      density lipoprotein cholesterol (HDL-C) was lower in the NIDDM group than in the
      controls. Significantly increased TC/HDL-C and LDL-C/HDL-C ratios were found in
      NIDDM patients compared with controls. The apolipoprotein A-I (apo A-I) and
      apolipoprotein A-II (apo A-II) levels were decreased in NIDDM patients, while the
      apolipoprotein B (apo B) level remained similar to that of the control subjects.
      The ratio of apo A-I/apo B was decreased significantly in the NIDDM group. Our
      results suggest that NIDDM patients are at higher risk of coronary heart disease,
      even if they remain normolipidemic.

PMID- 1358345
TI  - Clinical experience of octreotide in the treatment of acromegaly.
AB  - To evaluate the efficacy and safety of octreotide (a somatostatin analogue) in
      the treatment of acromegaly, 10 patients were injected subcutaneously with
      octreotide, 50 micrograms, thrice daily before each meal for two days, followed
      by 100 micrograms thrice daily for six months. One case dropped out at the
      initial stage because of diarrhea, and another quit due to a lack of improvement
      in headaches after treatment for three months. Eight patients completed the
      study. The results showed that the circumference of the fourth finger and hand
      volume significantly decreased after treatment. Laboratory data demonstrated that
      serum growth hormone (GH) and somatomedin-C levels also decreased significantly.
      However, in six patients without a history of trans-sphenoidal adenomectomy, the
      serum GH and somatomedin-C levels returned to normal in only one case who had a
      serum GH level < 20 mU/L before treatment. In the oral glucose tolerance test,
      paradoxic elevation of GH subsided after treatment. In the TRH test, paradoxic
      elevation of GH improved after treatment. In the bromocriptine test, octreotide
      had a synergistic effect on the suppression of GH. All cases had the side effect
      of injection pain, especially at the initial stage. An increase in intestinal
      peristalsis and bowel movement occurred in the first week, but symptoms later
      subsided. Two out of these eight patients had gallbladder sludge after six months
      of treatment. In conclusion, octreotide is effective in the treatment of
      acromegaly; however, it is better used in patients who have serum GH levels < 20
      mU/L, or after a trans-sphenoidal adenomectomy, and may be combined with
      bromocriptine to treat the patient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358346
TI  - Effects of fibrin glue on hemostasis.
AB  - In order to decrease complications following incomplete hemostasis, we tried to
      make a safe, efficient and highly concentrated fibrin glue by thawing single
      donor fresh frozen plasma. Using a unique animal model, in which arterial
      bleeding was created, fibrin glue and some related hemostatic agents were tested
      to evaluate their hemostatic effectiveness. The results demonstrated that: 1) the
      concomitant use of cryoprecipitate-thrombin tissue glue with adjuvant (aprotinin
      or calcium chloride) had a better hemostatic effect than the use of
      cryoprecipitate-thrombin tissue glue alone (p < 0.05); 2) impregnation of fibrin
      glue with a suitable vehicle was advisable to accelerate the coagulation plug
      formation and to enhance the mechanical strength of the adhesive plug; 3)
      Gelform, used as a vehicle to hold the fibrin glue, had a more efficient
      hemostatic effect than gauze, collagen fleece and Surgicel (p < 0.05); 4)
      systemic heparinization attenuated the effectiveness of the hemostatic agents and
      aggravated the bleeding problem, but a low hematocrit level did not; 5) fibrin
      glue had its own limitations, especially under systemic heparinization, on
      hemostatic effectiveness in a high-pressure system. Understanding the
      characteristics of fibrin glue, as mentioned above, definitely improved the
      hemostatic effectiveness of the glue, especially after failure of the usual
      methods of controlling bleeding.

PMID- 1358347
TI  - Characterization of a newly established human bladder carcinoma cell line, NTUB1.
AB  - A new human bladder cancer cell line, NTUB1, has been derived from the surgical
      specimen of a 70-year-old female patient diagnosed with poorly differentiated
      transitional cell carcinoma. It has been successfully propagated in vitro for
      over 24 months without evidence of reaching senescence. Population doubling time
      was about 21 hours at the 32nd passage. It was tumorigenic in nude mice, and the
      histologic findings of the heterotransplanted tumor resembled the original tumor.
      Expression of keratin proteins confirmed its epithelial origin. Cytogenetic
      analysis showed multiple chromosome changes. Anticancer drugs, including thiotepa
      and adriamycin, were tested in vitro, and the cytotoxicity did not exceed 50% of
      the control value; likewise, in this patient chemotherapy was not effective. On
      the other hand, a combination of recombinant tumor necrosis factor and interferon
      tau in vitro was more effective against this tumor.

PMID- 1358348
TI  - Evaluation of the A-60 IgG ELISA serodiagnostic test for tuberculosis in Taiwan.
AB  - To assess the applicability of a serologic test of specific IgG antibody for
      tuberculous infection in the Taiwan population, serum samples obtained from 118
      subjects were analyzed by an ELISA test using mycobacterial antigen 60. There
      were 50 patients with a documented active infection caused by Mycobacterium
      tuberculosis (39 pulmonary tuberculosis, five pleurisy, three cervical
      lymphadenitis and three miliary tuberculosis with extrapulmonary involvement). Of
      these 50 patients, 42 (84%) showed a positive ELISA test (titer > 200 U). Of the
      19 patients with inactive pulmonary tuberculosis, seven (37%) had a positive
      titer. Of the 22 patients with pulmonary disease other than tuberculosis, four
      (18%) showed a false-positive. In eight patients with autoimmune diseases, only
      the patient with rheumatoid arthritis had a positive reaction. One of the 19
      healthy controls (5.3%) showed a false-positive result. The overall false
      positive rate for the nontuberculous group was 12%. Follow-up examinations in 20
      patients with active tuberculosis one month after treatment revealed that seven
      had an elevation in titers (three of them were initially negative and became
      positive later), five remained high and eight decreased in titers. Further
      examinations in six patients two months after treatment showed a decrease in
      titers. We conclude that this ELISA assay of specific IgG antibody is a valuable
      serologic test for diagnosis of M. tuberculosis infection. It may be useful in
      areas with a high prevalence of M. tuberculosis infection.

PMID- 1358349
TI  - Gestational and congenital syphilis in Hualien.
AB  - From September 1987 to April 1991, 19 pregnant women (0.97%) with syphilis were
      detected out of 1,955 pregnant women who received prenatal serologic screening at
      the Buddhist Tz'u-Chi General Hospital. The ages ranged from 17 to 34 years
      (average, 26). Three cases had recurrent gestational syphilis. The time of
      diagnosis was: the third trimester, 11 cases; the second trimester, six cases;
      and the first trimester, two cases. The reasons for late (third trimester)
      diagnosis were: delay of prenatal care, four cases; failure to screen syphilis in
      the pregnancy, four cases; and negative first test and late infection, three
      cases. Late diagnosis and treatment often resulted in poor fetal outcome:
      syphilitic stillbirth, two cases; probable and possible congenital syphilis,
      seven cases; and normal infant, two cases. Patients (delivered, five;
      undelivered, two; abortion, one) who had been diagnosed before the third
      trimester had a better fetal outcome: possible congenital syphilis, one case; and
      normal infant, four cases. The perinatal mortality and morbidity were
      significantly higher in the late diagnosis group (9/11) than in the early
      diagnosis group (1/5). Pregnant women should be screened in early pregnancy by a
      serologic test for syphilis. In areas of high prevalence, or in patients at high
      risk, screening should be repeated in the third trimester and again at delivery.

PMID- 1358350
TI  - Aicardi's syndrome in a female infant with a family history of miscarried male
      siblings.
AB  - Aicardi's syndrome is thought to be an X-linked genetic disease, although the
      mechanism for transmission remains uncertain. We report on a four-month-old
      female patient with Aicardi's syndrome. She was born prematurely at 28 weeks'
      gestation, weighing 1,500 g. Asymmetric myoclonic jerks developed at one month of
      age. Her left eye showed chorioretinal lacunae and a coloboma on the optic disc,
      while the right eye was microphthalmic with total retinal detachment. A CT scan
      disclosed heterotopia and dysgenesis of the corpus callosum. Abnormal development
      of the thoracic vertebrae was also evident. The most remarkable aspect of this
      case was that the patient's mother had suffered three miscarriages. Two are known
      to have been male, but the other gender is unknown. This family history may
      support the theory that there is a factor, lethal for males, involved in the
      genetic transmission of Aicardi's syndrome.

PMID- 1358351
TI  - Resolution of cerebral white matter lesions following long-term penicillamine
      therapy for Wilson's disease: report of a case.
AB  - Although lenticular gray matter lesions in Wilson's disease (WD) may resolve
      following long-term decoppering therapy, response of cerebral white matter
      lesions to such a treatment has not been reported. A patient with WD developed
      dystonia of the left hand and focal seizures involving the left upper limb with
      occasional generalization. CT disclosed a low density area in the right frontal
      white matter. Initiation of penicillamine therapy resulted in worsening of
      clinical manifestations, further extension of the right frontal lesion, and
      development of a new left parietal lesion. However, after five years of continued
      penicillamine therapy, clinical improvements were noted, including disappearance
      of the left parietal lesion and almost complete resolution of the right frontal
      lesion. The present case suggests that cerebral white matter lesions in WD may
      also respond to long-term chelating therapy.

PMID- 1358352
TI  - Chronic recurrent multifocal osteomyelitis: report of a case.
AB  - We report on a Chinese boy with chronic recurrent multifocal osteomyelitis
      (CRMO). The eight-year-old boy presented with intermittent exacerbation and
      spontaneous remission of bone pain at two bone sites, associated with local
      erythema, swelling and tenderness. The white blood cell count, erythrocyte
      sedimentation rate, alkaline phosphatase, lactate dehydrogenase, calcium and
      phosphate were normal or mildly elevated. The roentgenogram and scintigram were
      consistent with osteomyelitis. The pathologic feature of the bone biopsy
      specimens was compatible with osteomyelitis. However, no organisms were
      consistently isolated from culture, and the disease was unaffected by
      antimicrobial therapy. CRMO is an uncommon childhood disease of still unknown
      etiology. It is the purpose of this paper to present our experience with the
      first case in a Chinese person and to review the literature with a discussion of
      what is currently known about CRMO.

PMID- 1358353
TI  - Internal mammary artery to pulmonary artery fistula associated with sick sinus
      syndrome: report of a case.
AB  - A 77-year-old woman presented with general weakness, dizziness and slow,
      irregular heart beats. An electrophysiologic study revealed a markedly prolonged
      sinus node recovery time of up to 5,900 msec, accompanied with dizziness. A
      permanent pacemaker with an AAIR mode was implanted. An abnormal shadow in the
      right lower lung field was found on chest x-ray. Selective arteriography revealed
      a right internal mammary to right pulmonary artery fistula. No significant
      hemodynamic abnormalities were found. This anomaly is extremely rare. Our patient
      is the oldest among 20 cases reported in the literature, and is the first one
      associated with sick sinus syndrome. Most reported cases have involved surgical
      ligation and excision, due to the risk of rupture of the malformation,
      endarteritis and congestive heart failure. Our patient refused surgical
      intervention and has done well during the past year.

PMID- 1358354
TI  - Desmoplasia and regression of lung adenocarcinoma after intratumor injection of
      OK-432: report of a case.
AB  - Intratumor injections of an immune modulator, OK-432, were administered to a 61
      year-old man with inoperable lung adenocarcinoma. He received intratumor
      injections of OK-432, 20 K.E., twice weekly, under chest ultrasound guidance. A
      total dose of 240 K.E. was given in a six-week period. The tumor size decreased
      during a six-month follow-up period after the OK-432 injections. The immunologic
      profile of the patient showed neutrophilia, a decrease in the lymphocyte count in
      the peripheral blood and an increase in immunoglobulins after the OK-432
      injections. The peripheral T-lymphocyte subsets showed a significant reduction in
      cytotoxic T cells and a decrease in the OKT4/OKT8 ratio. Histologic examination
      of the tumor after OK-432 injections showed extensive desmoplastic fibrosis.
      There was no evidence of lymphocyte infiltration. Intratumor injections of OK-432
      may be an alternative for local control of inoperable lung cancer.

PMID- 1358355
TI  - Familial nephrogenic diabetes insipidus: report of two families.
AB  - Familial nephrogenic diabetes insipidus is a hereditary disorder, generally
      transmitted by sex-linked recessive genes with varying degrees of penetrance in
      females. The onset of this disorder occurs in infancy, usually characterized by
      unexplained fever, recurrent dehydration and failure to thrive. If left
      unrecognized, recurrent hyperosmolality and hypernatremia will lead to retarded
      growth and neurologic sequelae. Intracranial hemorrhage, consciousness
      disturbance and even mortality may occur in cases of acute dehydration episodes.
      We report on two families with nephrogenic diabetes insipidus, whose various
      symptoms and signs were studied to establish an accurate diagnosis. In pediatric
      practices, it is very important to recognize early those infants with obscure
      symptoms in order to preserve their psychomotor development and growth potential.

PMID- 1358357
TI  - [Projected supply and geographic distribution of physicians in Taiwan for the
      year 2000].
AB  - Using the data from the Physician Masterfile of the Department of Health,
      Executive Yuan, and reports from all of the medical colleges in Taiwan and the
      Ministry of Defense, this study projects the future supply of physicians as well
      as their geographic distribution. The components of the projection include a
      study of current supply, future increments and losses. Three sources of future
      increments are identified: new native medical graduates, foreign medical
      graduates and medical transfers from the military. Age-specific and year-of
      graduation-specific active rates are used to estimate losses. The results of this
      study show: There will be 25,956 active physicians in Taiwan by the year 2000, or
      118 physicians per 100,000 people; and the ratio of the highest to the lowest
      (Taipei city vs Yunlin county) in terms of the physician-population ratio will
      become worse from 4.5 in 1990 to 5.4 in 2000, ceteris paribus. Finally, this
      study discusses the projection process as well as the implications for the
      physician manpower policy in Taiwan.

PMID- 1358356
TI  - Sciatica caused by piriformis muscle syndrome: report of two cases.
AB  - The diagnosis of piriformis muscle syndrome, an unusual cause of sciatica, is
      difficult. However, with the advancement of imaging techniques, it has become
      clear that the condition is not just clinical speculation, but is a definite
      entity. We report on two cases with piriformis muscle syndrome, diagnosed on the
      basis of: a history of sciatica; physical findings, such as a tender point at the
      sciatic notch and around the piriformis muscle by palpation of the gluteal
      region, and by a digital pelvic examination; and computed tomography (CT) to
      demonstrate hypertrophy of the piriformis muscle. In both cases, a tenotomy of
      the piriformis muscle at the greater trochanter relieved entrapment of the
      sciatic nerve and gave satisfactory results. Since local tenderness at the
      piriformis muscle is the most reliable physical finding, a pelvic examination is
      recommended in the evaluation of suspected cases of piriformis muscle syndrome.
      CT is helpful in showing hypertrophy of the piriformis muscle. Detailed history
      taking, a careful physical examination, and versatile use of CT or magnetic
      resonance imaging can lead to an early, accurate diagnosis and proper treatment.

PMID- 1358358
TI  - [A clinicopathological study in primary biliary cirrhosis].
AB  - Twenty-two patients with clinical, biochemical, immunological and pathological
      characteristics compatible with primary biliary cirrhosis were studied. There
      were 17 women and 5 men with a mean age of 57.4 +/- 15.2 years and a mean follow
      up of 24.1 +/- 20.1 months. Four of them expired during the follow-up and
      eighteen patients now survive. The most common complaints were fatigue (63.6%)
      and itching (59.1%). Only one case (4.5%) was asymptomatic in this series. The
      major physical findings were jaundice (50%) and hepatomegaly (50%). The
      significant laboratory findings were: elevation of alkaline phosphatase (91% of
      the cases greater than 3 times the upper limit of normal), gamma-glutamyl
      transpeptidase (100% of the cases greater than 4 times the upper limit of
      normal), aspartate transaminase (95%) and alanine transaminase (100%), presence
      of anti-mitochondrial antibodies (91%), antinuclear antibodies (73%) and the
      elevation of IgM (88%). One case was associated with ulcerative colitis.
      Pathological staging in this series revealed 57.9% of stage II, 26% of stage III,
      10% of stage IV and 5.3% of stage I. All patients with granuloma survived but 4
      of the 5 patients with cholestasis died during follow-up. The results show that
      the features in this series of PBC were similar to those observed in western
      countries. The very high ALP and gamma-GT level as well as only one asymptomatic
      case in this series, suggest that our patients were diagnosed at a late stage.
      The reason(s) for the higher positivity of ANA, particularly the speckled type
      and a lower rate of associated auto-immune disease requires further study. Liver
      biopsy in predicting a prognosis is valuable.

PMID- 1358360
TI  - [Dento-facial structural characteristics in Angle Class II malocclusion
      associated with abnormal facial divergency].
AB  - Lateral cephalometric radiographs of 60 adult patients with Angle class 11
      malocclusion associated with abnormal facial divergency were collected from the
      Orthodontic Department of the National Taiwan University Hospital. They were
      divided into a hyperdivergent group (35 cases) and a hypodivergent group (25
      case), according to mandibular plane angle (SN-MP). The 19 landmarks on each
      cephalometric tracing were digitized into a computer, then computer-aided
      cephalometric analysis was performed to calculate the 17 skeletal measurements
      and 13 dentoalveolar measurements. The dento-facial structural characteristics of
      the hyperdivergent and hypodivergent groups were compared. It was found that the
      subjects of the hyperdivergent group revealed a greater tendency of divergency in
      the anterior cranial base plane, Frank-fort horizontal plane, palatal plane,
      occlusal plane, and mandibular plane. Hyperdivergent facial type, supposedly
      indicating an open bite or a tendency toward an open bite, has a longer lower
      anterior facial height, shorter posterior facial height, longer upper anterior
      and posterior dental height. While, the majority of dentofacial characteristics
      of the hypodivergent facial type observed in is study were directly opposite to
      those of the hyperdivergent facial type. The relationships of incisor overbite
      depth and other skeletal and dentoalveolar parameters were illustrated by
      Pearson's correlation coefficient and stepwise multiple regression analysis by
      means of the SPSS/PC statistic program. With the incisor overbite depth as the
      dependent variable, the independent variables included on the regression analysis
      were the 10 items of skeletal and dentoalveolar parameters. The compared
      parameters showed a statistically significant correlation with the incisor
      overbite depth (P < 0.001). By the stepwise method, the variables included on the
      regression equation were (1) N-Go-Gn, (2) A-Gn-Ar, (3) N-Ans/ans-Me, and (4)
      U1L1. The value of R square (R2) in the regression analysis was 0.543. It
      demonstrated that only a 54.3% variation in incisor overbite depth can be
      explained by variations in those skeletal and dentoalveolar variables.

PMID- 1358359
TI  - [Factors in recurrence after curative resection of rectal cancer].
AB  - Data on 409 Patients who had a curative resection for rectal cancer at the
      National Taiwan University Hospital between 1977 and 1989 were analysed to
      determine the independent effect on recurrence. In our series, the total
      operative mortality rate was 1.7% and the resectability rate was 88.1%. For these
      cases who received curative resection, the overall 5-year survival rate was
      62.6%. The 5-year survival rate varied according to the Dukes' stage: stage A,
      96.4%; stage B, 73.3% and stage C, 39.6%. The total recurrence rate after
      curative resection was 35.9%, including local recurrence 18.3%, systemic
      recurrence 12.0%, and combined recurrence 5.6%. According to Dukes' staging
      system, the recurrence rate for stage A, B and C were 0%, 22.4% and 63.8%,
      respectively. We used Cox's regression model to analyse the patients
      characteristics and pathological variables on recurrence and to assess the
      independent influence of each when all other factors were held constant. The
      pathological stage of the cancer had the strongest association. Other variables
      found to have an independent yet significant importance, were CEA level and tumor
      size. The identification of the patient group, at a high risk of recurrence,
      might promote a more judicious selection for surgical procedure and trials of
      adjuvant therapy.

PMID- 1358362
TI  - [Peutz-Jeghers syndrome: report of two cases and review of the literature].
AB  - Two cases brothers of Peutz-Jeghers syndrome are reported, in which the
      gastrointestinal polyps were resected by laparotomy and enterotomy. One of the
      polyps was in the cecum and was found to have atypia cellular change, though no
      malignancy was found in the others, which were thought to be hamartomas. The
      hamartomatous polyps were initially thought to have little potential for
      malignancy, and the disease was believed to have a relatively benign course.
      However, reports in the literature have associated this syndrome with various
      kinds of malignancies, and the overall risk of cancer in this population is
      regarded as higher than normal. The analysis of our cases and a review of the
      literatures are presented for clarification of the predisposition of the
      development of malignancies in these patients.

PMID- 1358361
TI  - [Mouse embryos co-cultured with various generations of human ampullary cells].
AB  - The pregnancy rates for the gamete intra-fallopian transfer (GIFT) and tubal
      embryo transfer (TET) methods have been shown to be high. The oviductal
      environment appears to be suitable for fertilization and subsequent cleavage.
      Many authors have reported that when co-cultured with human ampullary cells, the
      embryos can develop in vitro as well as in vivo. Thus, significantly more embryos
      reach the early blastocyst stage, and more successful implantation may be
      obtained. However, the characteristics of the ampullary cells may change after a
      series of sub-cultures. In this study, we compared the first and the seventh sub
      culture ampullary cell co-cultured systems with a control group. There were
      significantly more embryos cleaved to blastocysts in these two co-cultured
      systems than in the control group, but no significant difference between these
      two co-cultured systems. Detoxification of the medium by co-cultured cells may
      play an important role in improving embryo quality.

PMID- 1358363
TI  - [Kaposi's sarcoma in Tainan: report of five cases].
AB  - Kaposi's sarcoma (KS) is an uncommon cutaneous neoplasm with an increased
      incidence among Jews and Italians of Europe and North America and Negroes of
      equatory Africa. In recent years, several cases have been diagnosed in AIDS
      patients and in patients who have undergone organ transplantation or received
      immunosuppressant treatments. We have diagnosed five cases of KS over a 3-year
      period in our department. They include four men and one women, aged from 58 to 79
      years, and who were born and had lived in Tainan. They all denied a history of
      homosexuality, multiple sexual partners, or drug abuse. HIV (Human
      immunodeficiency virus) screening test were negative. Two patients had taken
      'black pills' (usually containing steroids) for a long period of time and also
      had generalized dermatophytosis. One of these two patients had a cytomegalovirus
      infection and died of Salmonella septicemia and upper GI bleeding. Although the
      English literature seems to indicate that KS is rare among Asians. Our present
      experience coupled with two other recently reported cases from Taiwan and the
      unpublished observations of some other dermatologists suggest that KS is not all
      that rare in Taiwan.

PMID- 1358364
TI  - [Continuous arteriovenous hemodialysis in critical patients with acute renal
      failure].
AB  - Continuous arteriovenous hemodialysis (CAVHD) offers a modified therapeutic
      approach for the patient with acute renal failure. The system is modified fron
      the CAVH write out method by adding two pumps to control the flow rate of the
      dialysis solution and to reduce the nursing load. The blood flow through the
      dialyzer is dependent on the net blood pressure gradient. Peritoneal dialysis or
      bicarbonate dialysate is infused through the dialysate ports utilizing both
      diffuse and convective transport for an average blood flow rate of 0.9 L/hour.
      The two pumps control the dialysate inflow and outflow rates. Ten patients with
      complications and acute renal failure were treated with CAVHD for periods ranging
      from 10 to 154 hours. Average urea clearance was 9.39 mL/min. Average creatinine
      clearance was 9.12 mL/min, and in stable patients, the mean BUN was maintained at
      60 mg/dL and the mean serum creatinine level was 4.6 mg/dL. The average
      ultrafiltration rate obtained was 100 mL/hr and was adjusted for the body fluid
      condition. most patients tolerated CAVHD without further hemodynamic instability
      and did not develop serious complications. In conclusion, CAVHD is a safe and
      technically simple procedure, which is particularly suitable for hemodynamically
      unstable patients requiring fluid removal.

PMID- 1358365
TI  - [Laparoscopic orchiectomy for intraabdominal cryptorchism and varicocelectomy].
AB  - Laparoscopic procedures have recently been used in the evaluation and treatment
      of some urogenital diseases. A case of right intraabdominal cryptorchism
      associated with left varicocele was successfully treated by laparoscopic
      orchiectomy and ligation of the contralateral internal spermatic vein
      concomitantly. This new technology can be easily performed and has the advantages
      of less tissue trauma, easy application for bilateral lesions, and less patient
      morbidity. We consider laparoscopy is a promising method for the diagnosis and
      treatment of intraabdominal testis.

PMID- 1358366
TI  - [CT and MRI of parasellar cavernous hemangioma in two cases].
AB  - Extracerebral cavernous hemangioma is a rare entity, only 51 cases have been
      reported up to 1991. Most of the extracerebral cavernous angiomas occur in the
      parasellar region and easily extend to the sella; with CT and MRI views entirely
      different from those of intracerebral cavernous hemangiomas. The CT scan shows a
      good, homogeneous enhanced tumor, similar to a meningioma, yet lacking
      calcification or bony hyperostosis. In MRI, the characteristic findings of
      extracerebral cavernous hemangioma are the very high signal intensity in the T2
      weighted image, and strong homogeneous enhancement by Gadolinium-DTPA. Here we
      report two cases of parasellar cavernous hemangioma. A 68-year-old male patient
      shown to have a dumbbell tumor in the parasellar and sellar regions by CT scan,
      showed a high density before contrast, and good enhancement by an iodine
      contained contrast medium. The tumor had a very high signal intensity in the T2
      weighted image of MRI and a good, homogeneous enhancement by Gadolinium-DTPA, yet
      a carotid angiogram showed it was avascular. Surgical removal was abandoned in
      view of the probability of massive bleeding. The second case was a 34-year-old
      man, who had had a skin hemangioma on the right side of the face since his
      childhood. For the past 3 months, he had suffered from ptosis, and limitation of
      eye movement which was found to be due to 3rd and 4th cranial nerve palsy. CT
      showed a good enhanced tumor mass in the left side of the parasellar region with
      sellar extension. MRI also showed a high intensity in T2WI and good, homogeneous
      enhancement by Gadolinium-DTPA. A carotid angiogram revealed some tumor stain.
      Surgical removal. in this case, was also impossible due to its intracavernous
      sinus location and the probability of massive bleeding.

PMID- 1358367
TI  - [Enzyme cytochemistry of microcylinders: a Long-Evans-rat-specific mitochondrial
      inclusion].

PMID- 1358368
TI  - [Study on P450c21 gene].
AB  - Yeast cells harboring mutant plasmids were incubated with 0.1, 0.15, 0.2, 0.3,
      0.4, 0.45, 0.6, or 1.0 mM (14C)-17-hydroxyprogesterone for 1h. The steroids in
      the media were then separated by thin layer chromatography and counted to
      calculate enzymatic activities. Wt = wild type enzyme. Pt: patient enzyme.

PMID- 1358369
TI  - [High-resolution chromosome techniques].

PMID- 1358370
TI  - [Detection of chimerism after bone marrow transplantation].

PMID- 1358371
TI  - [Willingness to share costs of health insurance].
AB  - The purpose of this investigation, undertaken in 1988, was to find out citizens'
      willingness to share the costs of health insurance in metropolitan Taipei. The
      individuals sampled were from three groups: government employee insurer GEI,
      Labor insurer LI, and others OT. A stratified random sampling method and a closed
      format questionnaire were used in this study. A total of 300 samples were taken
      from GEI, 500 form LI and 300 from OT. The total number of effective
      questionnaires were 1065. The questionnaire had 8 parts including individual
      basic data, consciousness of self health conditions, knowledge of LI, knowledge
      of GEI, degree of satisfaction with medical services, medical care utilization,
      willingness of health insurance, and willingness to share costs. The results
      showed that most people pay, most respondents would only be willing to pay a
      limited amount. The different factors positively influencing a willingness to
      cost share were level of education, average income and knowledge of health
      insurance, while the degree of satisfaction towards medical services was a
      negative influence. Since the public is not yet willing to accept a cost-sharing
      system, this study was of limited value in trying to find out the explanatory or
      predicting factors. Nevertheless, because of the negative reactions of
      respondents, we are obliged to more carefully and circumspectly rethink the
      implementation of a cost-sharing system.

PMID- 1358372
TI  - Ipriflavone: A New Non-Hormonal Therapeutic Agent in Osteoporosis. Satellite
      symposium proceedings. Florence, Italy, April 24, 1992.

PMID- 1358373
TI  - General practitioners' management of hypertension in elderly patients.
AB  - OBJECTIVE: To assess general practitioners' attitudes to the diagnosis and
      management of hypertension in elderly patients. DESIGN: Postal questionnaire to
      all general practitioners in Leicestershire. RESULTS: 360 of 451 general
      practitioners (80%) responded. 81% (292) reported rechecking an initially high
      blood pressure on two or three occasions before starting treatment, 56% (202)
      measured sitting blood pressure only, and just 28% (100) took sitting and
      standing levels. 36% (128) had no upper age limit for starting anti-hypertensive
      treatment; of the 58% (206) who did, the median was 80 (range 70-99) years. Blood
      pressure levels reported for starting treatment in patients aged 70-79 years were
      180 (150-240)/106 (90-120) mm Hg. 34% of general practitioners (121) would not
      treat isolated systolic hypertension. The most popular first line treatment for
      an elderly hypertensive patient was a thiazide diuretic; only 17% of general
      practitioners (61) initially tried non-pharmacological methods. 34% (122) would
      continue anti-hypertensive treatment unchanged in the period immediately after
      stroke. CONCLUSIONS: The variation among general practitioners in the criteria
      for the measurement, diagnosis, and treatment of hypertension in elderly patients
      emphasises the need for clear management guidelines in this age group.

PMID- 1358374
TI  - Ecstasy and the dance of death.

PMID- 1358375
TI  - [The effect of an alpha-adrenoblocker and a calcium-channel blocker on the
      spontaneous tonus of an isolated blood-perfused artery].
AB  - The existence of spontaneous myogenic tone was shown on an experimental model of
      an isolated artery perfused "ex vivo" with blood from the rat donor.
      Administration of the alpha-adrenoblockers prasosine and yohimbine into the
      perfusion medium in the bath was followed by a 60% decrease in the myogenic tone.
      The nonspecific blocker of calcium channels CaCl2 decreased the rest of the tone
      by 15%. The remaining 20-25% of the initial myogenic tone was inhibited by sodium
      nitroprusside. Urethane (300 mg/kg) or nembutal (20 mg/kg) injected intravenously
      into the rat donor may lead to an increase or a decrease in the myogenic tone,
      respectively. The conclusion is made that the advantage of the experimental model
      proposed lies in the existence of the spontaneous myogenic tone of an arterial
      vessel depending on humoral catecholamines and some other vasoconstrictor
      factors.

PMID- 1358376
TI  - [The mechanism of the antiarrhythmic action of dalargin in experimental
      myocardial ischemia].
AB  - It has been found that injection of dalargin before the occlusion of the left
      anterior coronary artery prevents an increase of cAMP content in the myocardium
      and blood plasma. In the myocardium of rats given dalargin before acute
      myocardial ischemia, the content of cGMP was increased and the level of
      somatostatin was reduced. It is assumed that the increase of the content of cGMP
      and the reduction of cAMP and somatostatin levels in the myocardium play an
      important role in antiarrhythmic action of dalargin.

PMID- 1358377
TI  - [The effect of the new nonsteroidal anti-inflammatory agent glucamine on
      oxidative phosphorylation processes].
AB  - A study was made of the action of the nonsteroidal antiinflammatory agent
      glucamin on the processes of oxidation and phosphorylation (OP) in isolated
      mitochondria of the liver. It has been established that glucamin does not exhibit
      the properties of a separator in the explored concentrations (10(-2)-10(-7) M).
      Unlike the standard drug voltaren that separates OP processes, it slightly
      enhances interaction of liver mitochondria which oxidize NAD-dependent
      substrates. The effect of voltaren is dose-dependent, being pronounced to a
      greater measure when succinate is applied as a substrate of mitochondria
      oxidation.

PMID- 1358378
TI  - Experience with peripheral blood stem cell collection for autografts in children
      with active cancer.
AB  - This report examines laboratory and clinical experience with peripheral blood
      stem/progenitor cell harvest for autografts in 71 consecutively referred children
      with various types of cancer from one institution. The age of the patients ranged
      from 7 months to 17 years with a median of 8 years. Ten of the 71 referred
      children were removed from the collection procedure because of failure to induce
      clinical remission (nine) or deteriorating chemotherapy-induced liver failure
      (one). A total of 215 aphereses were performed on a CS 3000 cell separator in 61
      patients, including 18 children aged 4 years or less. The methylcellulose
      progenitor assay was used as an index of stem cell collection. A minimum of
      greater than or equal to 3 x 10(5) colony-forming units-granulocyte/macrophage
      (CFU-GM)/kg body weight were collected in 31 of 71 children (44%) with a mean of
      3.1 (range, 1-5) aphereses, and greater than or equal to 1 x 10(5) CFU-GM/kg in
      46 children (65%). The incidence of serious morbidity was low. When apheresis or
      chemotherapy was repeated, the progenitor yields decreased rapidly. By
      multivariate analysis, the age of the patients was the only significant predictor
      of CFU-GM yield (p = 0.009). In our experience with 12 children with acute
      leukemia or non-Hodgkin's lymphoma, regimens containing high-dose cytarabine (2.0
      g/m2 x 10) were effective for mobilization. Our results extend the earlier
      findings that harvesting PBSCs for autografts in children with active cancer is a
      safe and reliable procedure with a low incidence of serious morbidity.

PMID- 1358379
TI  - Prompt haemopoietic reconstitution following hyperthermia purged autologous
      marrow and peripheral blood stem cell transplantation in acute myeloid leukaemia.
AB  - We report a case of acute myeloid leukaemia in a 35-year-old woman where marrow
      and chemotherapy-mobilized peripheral blood stem cells (PBSC) were obtained in
      first complete remission and heat treated at 42 degrees C for 1 h to minimize the
      likelihood of leukaemic relapse. Transplantation of marrow and PBSC was
      undertaken following busulphan/cyclophosphamide conditioning 9 months after
      diagnosis in CR1. Hyperthermic purging did not impair the rate of engraftment and
      the patient was independent of blood product support by day 21. Studies on this
      patient's committed normal granulocyte-macrophage progenitor cells (CFU-GM) on
      samples from marrow and peripheral blood following treatment at 42 degrees C for
      1 h, showed minimal and acceptable loss of activity comparable with the loss seen
      in other marrow progenitor activity treated in a similar fashion in our
      laboratory. We conclude that hyperthermia-purged PBSC can be used to hasten
      recovery in autologous haemopoietic progenitor transplantation without
      compromising rate of engraftment. This is part of an ongoing pilot study to
      evaluate the role of hyperthermic purging to reduce the risk of leukaemic
      relapse.

PMID- 1358380
TI  - Characterization of adrenoceptors involved in the electrogenic chloride secretion
      by cultured rat epididymal epithelium.
AB  - 1. Short-circuit current (SCC) technique was used to study the adrenoceptors
      involved in the electrogenic chloride secretion by cultured cauda epididymal
      epithelium of rats. Stimulation of the epithelium with noradrenaline (primarily
      beta 1-adrenoceptor selective agonist), salbutamol (beta 2-adrenoceptor selective
      agonist) and adrenaline (non-selective beta-adrenoceptor agonist) led to a rise
      in SCC. At a low chart-speed (2 mm min-1), the response profile to these agonists
      consisted of a peak followed by a sustained response considerably higher than the
      basal SCC. 2. The EC50s (doses of agonist producing 50% maximum response) of
      noradrenaline, salbutamol and adrenaline were 300, 115 and 10 nM respectively.
      Pretreating the tissues with 1 microM atenolol (beta 1-selective antagonist) and
      10 microM butoxamine (beta 2-selective antagonist) shifted the dose-response
      curves of noradrenaline (shifted EC50 = 4000 nM) and salbutamol (shifted EC50 =
      1050 nM) to the right. Atenolol (1 microM) and butoxamine (10 microM) shifted the
      dose-response curve of adrenaline to the right with new EC50s of 30 nM and 115
      nM, respectively. 3. The rapidly rising phase of the SCC response to
      noradrenaline and adrenaline observed at low chart-speed consisted of a brief and
      transient retraction followed by a rebound increase in SCC. At a high chart-speed
      (1 mm s-1), the retraction and rebound phenomenon manifested as a fast initial
      spike which could be blocked by phentolamine (non-specific alpha-adrenoceptor
      antagonist) in a dose-dependent fashion. Similar initial spikes were observed
      when the tissues were stimulated with phenylephrine (alpha-selective agonist) but
      not with isoprenaline (non-selective beta-agonist) or forskolin (activator of
      adenylate cyclase). The response of the initial spike triggered by noradrenaline
      was dose-dependent and the EC50 was 2000 nM.4. The present study showed that the
      electrogenic chloride secretion by rat epididymis could be stimulated by (alphaxi
      , beta131- and beta2-adrenoceptor agonists. The al-mediated response had a faster
      onset and more transient action than the 3-counterpart. It is postulated that
      epididymal chloride secretion might be regulated by neural (noradrenaline
      mediated) and humoral (adrenaline-mediated) controls and that the stimulus
      secretion coupling mechanisms might involve both Ca2+(alpha-mediated response)
      and adenosine 3':5'-cyclic monophosphate (beta-mediated response) as
      intracellular second messengers.

PMID- 1358382
TI  - Involvement of nitric oxide pathway in the PAF-induced relaxation of rat thoracic
      aorta.
AB  - 1. The mechanism of the vasorelaxant effect of platelet activating factor (PAF)
      on rat thoracic aorta and the effect of aging on the PAF-induced relaxation were
      investigated. 2. PAF at concentrations causing relaxation induced marked
      increases in guanosine 3':5'-cyclic monophosphate (cyclic GMP) production, but
      did not induce an increase in adenosine 3':5'-cyclic monophosphate (cyclic AMP).
      3. Removal of the endothelium by mechanical rubbing, and treatment with the PAF
      antagonists CV-3988, CV-6209 and FR-900452, the nitric oxide biosynthesis
      inhibitor, NG-nitro L-arginine, the radical scavenger, haemoglobin, and the
      soluble guanylate cyclase inhibitor, methylene blue, inhibited PAF-induced
      relaxation and abolished or attenuated PAF-stimulated cyclic GMP production. 4.
      The relaxation was greatest in arteries from rats aged 4 weeks. With an increase
      in age, the response of the arteries to PAF was attenuated. 5. Endothelium
      dependent cyclic GMP production also decreased with increase in age of the rats.
      6. These results suggest that PAF stimulates production of nitric oxide from L
      arginine by acting on the PAF receptors in the endothelium, which in turn
      stimulates soluble guanylate cyclase in the smooth muscle cells, and so increases
      production of cyclic GMP, thus relaxing the arteries. Age-associated decrease in
      PAF-induced relaxation may result from a reduction of cyclic GMP formation.

PMID- 1358383
TI  - Determination of alpha 1-adrenoceptor subtype selectivity by [3H]-prazosin
      displacement studies in guinea-pig cerebral cortex and rat spleen membranes.
AB  - 1. [3H]-prazosin homogeneously labels alpha 1-adrenoceptors in guinea-pig
      cerebral cortex and rat spleen membranes with dissociation constants of 1.28 and
      1.49 x 10(-10) M respectively. 2. Phentolamine and WB 4101 displacement studies
      show that guinea-pig cerebral cortex contains 30% alpha 1A- and 70% alpha 1B
      adrenoceptor subtypes, whereas rat spleen contains a virtually homogeneous alpha
      1B-adrenoceptor subtype population. The alpha 1-adrenoceptor population of rat
      thoracic aorta is predominantly of the alpha 1A-adrenoceptor subtype, and in
      guinea-pig thoracic aorta it is mainly of the alpha 1B-adrenoceptor subtype. 3.
      Half of the compounds displacing [3H]-prazosin bound to guinea-pig cerebral
      cortex membranes display alpha 1A-adrenoceptor selectivity. Among these
      compounds, WB 4101 and methoxamine are most selective, displaying selectivity
      ratios of approximately 38 and approximately 26 respectively. 4. The affinity
      constants of the non-selective compounds for the alpha 1-adrenoceptor in guinea
      pig cerebral cortex membranes correlate well with the affinity constants obtained
      for alpha 1B-adrenoceptors in rat spleen membranes. The affinities of selective
      compounds for the alpha 1B-adrenoceptor subtype in guinea-pig cerebral cortex
      correlate very well with their affinity for alpha 1B-adrenoceptor in the rat
      spleen homogenate. Both regression lines coincide with the line of identity. The
      affinity constants of selective compounds for the alpha 1A-adrenoceptors in
      guinea-pig cerebral cortex only apparently correlate with the affinity for either
      the alpha 1B-adrenoceptors in guinea-pig cerebral cortex or in the rat spleen.
      Regression analyses indicate a straight line relationship (r2>0.9) between pKEA
      and Pk1B but the regression lines deviate from the line of identity.

PMID- 1358384
TI  - Different patterns of protein kinase C redistribution mediated by alpha 1
      adrenoceptor stimulation and phorbol ester in rat isolated left ventricular
      papillary muscle.
AB  - 1. In rat left ventricular papillary muscle, phenylephrine, an alpha 1
      adrenoceptor agonist, had a staurosporine-sensitive positive inotropic effect and
      increased the particulate-associated protein kinase C (PKC) activity without
      significant changes in total PKC activity or in cytosolic Ca2+/phospholipid
      independent kinase (PKI) activity. 2. A PKC stimulant, phorbol 12,13-dibutyrate
      (PDBu), decreased contractility and slightly increased PKC activity in the
      particulate fractions, with a marked decrease and increase in total PKC and PKI
      activities, respectively. 3. The PDBu-induced negative inotropic response was
      attenuated by two protease inhibitors, leupeptine and a microbial peptide
      isolated from Aspergillus japonicus (E-64), which are known to inhibit the
      conversion of particulate-associated PKC to PKI. 4. Such differences in the
      patterns of PKC redistribution, i.e. marked increases in particulate PKC and
      cytosolic PKI activities caused by phenylephrine and PDBu, respectively, may
      account for the opposite inotropic effects of PKC stimulation by an alpha 1
      agonist and a phorbol ester.

PMID- 1358381
TI  - The effects of beta 2-adrenoceptor agonists and a corticosteroid, budesonide, on
      the secretion of inflammatory mediators from monocytes.
AB  - 1. The in vitro effects of the beta 2-adrenoceptor agonists (1 x 10(-9)-10(-5)
      M), terbutaline, salmeterol, and formoterol, on the release of inflammatory
      mediators, i.e. the eicosanoids leukotriene B4 (LTB4) and prostaglandin E2 (PGE2)
      and the cytokine interleukin-1 beta (IL-1 beta), were assessed in cultures of
      human blood monocytes. For comparison, the effects of a 5-lipoxygenase inhibitor,
      BW A4C (1 x 10(-9)-10(-5) M), and a corticosteroid, budesonide (1 x 10(-10)-10(
      5) M) were also examined. Sotalol was used to investigate whether the actions of
      beta 2-agonists were mediated through beta-adrenoceptors. 2. Terbutaline, like
      budesonide, had no significant effect on LTB4 release, whereas BW A4C (IC50 = 2 x
      10(-8) M) was a potent inhibitor. All concentrations of formoterol approximately
      halved the LTB4 secretion, whereas high concentrations (1 x 10(-7)-10(-5) M)
      only, of salmeterol, inhibited release. Only salmeterol, at high concentrations
      (greater than 1 x 10(-6) M), lowered the secretion of PGE2 in monocyte cultures.
      Formoterol and salmeterol reduced the secretion of IL-1 beta only at the highest
      dose (1 x 10(-5) M). In contrast, budesonide (greater than or equal to 1 x 10(-9)
      M) was a potent suppressant of this secretion. 3. Treatment of monocyte cultures
      with sotalol (1 x 10(-5) M) did not significantly antagonize the inhibitory
      effects of salmeterol and formoterol. These results suggest that the inhibitory
      action of these beta 2-agonists on the release of eicosanoids or IL-1 beta, is
      not mediated via beta 2-adrenoceptors.4. This study does not support a
      therapeutic importance of the anti-release effects of beta2-agonists since high
      concentrations were generally required. Furthermore, the anti-secretory action of
      beta2-agonists was distinct from that of corticosteroids.

PMID- 1358385
TI  - The alpha 2-adrenoceptors of the human retinoblastoma cell line (Y79) may
      represent an additional example of the alpha 2C-adrenoceptor.
AB  - 1. In agreement with the literature, correlation of the ability of a series of
      agonists and antagonists to displace [3H]-rauwolscine binding shows the alpha 2
      adrenoceptors of HT29 cells, NG108-15 cells, OK cells and homogenates of rat
      sublingual gland to represent four distinct subtypes. 2. [3H]-rauwolscine also
      bound with high affinity (KD = 0.30 +/- 0.10 mM) to a human retinoblastoma cell
      line (Y79). Specific binding represents 73% of total binding, and a Bmax of 38 +/
      1 fmol mg-1 protein was determined. 3. Correlation of antagonist affinities
      against [3H]-rauwolscine with corresponding values in the other four tissue
      sources showed the Y79 cells to resemble most closely the OK cells, the prototype
      example of an alpha 2C-adrenoceptor, with a correlation coefficient of 0.90 and a
      regression slope of 1.01 being obtained for 10 antagonists in these two systems.
      4. Comparison of KD values for [3H]-rauwolscine also showed a similarity between
      the OK cells (0.19 +/- 0.07 nM) and Y79 cells. 5. These data suggest that the
      human retinoblastoma cell line may represent an additional example of the alpha
      2C-adrenoceptor subtype.

PMID- 1358387
TI  - Modulation of non-adrenergic non-cholinergic inhibitory neurotransmission in rat
      gastric fundus by the alpha 2-adrenoceptor agonist, UK-14,304.
AB  - 1. The influence of the alpha 2-adrenoceptor agonist, UK-14,304, on non
      adrenergic non-cholinergic (NANC) relaxation induced by electrical field
      stimulation was investigated in longitudinal muscle strips of the gastric fundus
      of reserpinized rats. 2. In tissues where tone was raised by 3 x 10(-7) M
      prostaglandin F2 alpha (PGF2 alpha), the inhibitory effect of 10(-6) M UK-14,304,
      on the NANC relaxations induced by short train stimulation (40 V, 1 ms, 20 s) was
      inversely related to the stimulus frequency (1-4-16 Hz). UK-14,304 (10(-6) M) did
      not influence relaxations induced by administration of exogenous nitric oxide
      (NO, 2 x 10(-6) M-10(-4) M). The inhibitory effect of UK-14,304 on the
      electrically induced relaxations was antagonized by 10(-6) M rauwolscine but not
      by 10(-6) M prazosin. 3. UK-14,304 (10(-6) M) also reduced the amplitude of the
      sustained NANC relaxation, induced by electrical field stimulation (40 V, 1 ms, 4
      Hz) for 5 min. The effect of UK-14,304 was also antagonized by 10(-6) M
      rauwolscine but not by 10(-6) M prazosin. UK-14,304 (10(-6) M) did not reduce the
      relaxation induced by 3 x 10(-9) M vasoactive intestinal polypeptide (VIP). 4.
      These results suggest that the release of the inhibitory NANC neurotransmitter
      during short train stimulation, thought to be NO, and during sustained
      stimulation, thought to be VIP, is inhibited by stimulation of presynaptic alpha
      2-adrenoceptors in the rat gastric fundus.

PMID- 1358386
TI  - Pharmacological characterization of presynaptic alpha 2-autoreceptors in rat
      submaxillary gland and heart atrium.
AB  - 1. The pharmacological properties of presynaptic alpha 2-autoreceptors were
      studied in rat isolated submaxillary glands and atria. Tissue pieces were
      preincubated with [3H]-noradrenaline, then superfused with medium containing
      desipramine, and stimulated electrically. In one series of experiments, pEC30
      values of 12 alpha-adrenoceptor antagonists were determined, i.e., negative
      logarithms of concentrations that increased the electrically evoked overflow of
      tritium by 30%. In another series, pKD values of 9 alpha-adrenoceptor antagonists
      against the release-inhibiting effect of 5-bromo-6-(2-imidazolin-2-ylamino)
      quinoxaline (UK 14304), and of 3 antagonists against the release-inhibiting
      effect of methoxamine, were determined. 2. In submaxillary glands, the pEC30
      values of the antagonists correlated well with their pKD values against UK 14304
      (r = 0.93). The same was true for atria (r = 0.92). 3. In submaxillary glands,
      the pKD values of 3 antagonists against UK14304 were very similar to their pKD
      values against methoxamine, with a maximal difference of 0.4. The same was true
      for atria where the maximal difference was 0.3. 4. The pEC30 values obtained in
      submaxillary glands correlated significantly with those obtained in atria (r =
      0.81). The same was true for the pKD values (r = 0.79). However, the pEC30 and
      pKD values also indicated consistent differences between the two tissues. 5. It
      is concluded that the sites of action of the imidazoline UK 14304 (alpha 2
      selective), the phenylethylamine noradrenaline, and the phenylethylamine
      methoxamine (alpha 1-selective) are exclusively alpha 2-adrenoceptors. There is
      no indication for presynaptic alpha 1-adrenoceptors or for an effect of UK 14304
      mediated by presynaptic imidazoline receptors.The 02-autoreceptor population in
      the submaxillary gland differs from that in the atrium.6. Comparison with studies
      from the literature indicates that the submaxillary autoreceptors are closely
      similar to the a2D radioligand binding site found in the bovine pineal gland and
      probably the rat submaxillary gland. The atrial autoreceptors also conform best
      to this site, but the agreement is more limited; the atrial autoreceptors may
      represent a type related to, but distinct from, the a2D site, or a mixture of
      different types.

PMID- 1358388
TI  - Imidazoline antagonists of alpha 2-adrenoceptors increase insulin release in
      vitro by inhibiting ATP-sensitive K+ channels in pancreatic beta-cells.
AB  - 1. Islets from normal mice were used to study the mechanisms by which imidazoline
      antagonists of alpha 2-adrenoceptors increase insulin release in vitro. 2.
      Alinidine, antazoline, phentolamine and tolazoline inhibited 86Rb efflux from
      islets perifused with a medium containing 3 mM glucose, i.e. under conditions
      where many adenosine 5'-triphosphate (ATP)-sensitive K+ channels are open in the
      beta-cell membrane. They also reduced the acceleration of 86Rb efflux caused by
      diazoxide, an opener of ATP-sensitive K+ channels. 3. ATP-sensitive and voltage
      sensitive K+ currents were measured in single beta-cells by the whole-cell mode
      of the patch-clamp technique. Antazoline more markedly inhibited the ATP
      sensitive than the voltage-sensitive current, an effect previously observed with
      phentolamine. Alinidine and tolazoline partially decreased the ATP-sensitive K+
      current. 4. The four imidazolines reversed the inhibition of insulin release
      caused by diazoxide (through opening of ATP-sensitive K+ channels) or by
      clonidine (through activation of alpha 2-adrenoceptors) in a concentration
      dependent manner. Only the former effect correlated with the ability of each drug
      to increase control insulin release stimulated by 15 mM glucose alone. 5. It is
      concluded that the ability of imidazoline antagonists of alpha 2-adrenoceptors to
      increase insulin release in vitro can be ascribed to their blockade of ATP
      sensitive K+ channels in beta-cells rather than to their interaction with the
      adrenoceptor.

PMID- 1358389
TI  - Investigations into neuropeptide Y-mediated presynaptic inhibition in cultured
      hippocampal neurones of the rat.
AB  - 1. We have examined the effects of neuropeptide Y (NPY) on synaptic transmission
      and [Ca2+]i signals in rat hippocampal neurones grown in culture. [Ca2+]i in
      individual neurones displayed frequent spontaneous fluctuations often resulting
      in an elevated plateau [Ca2+]i. These fluctuations were reduced by tetrodotoxin
      (1 microM) or combinations of the excitatory amino acid antagonists 6-cyano-7
      dinitro-quinoxaline (CNQX) (10 microM) and aminophosphonovalerate (APV) (50
      microM), indicating that they were the result of glutamatergic transmission
      occurring between hippocampal neurones. 2. [Ca2+]i fluctuations were also
      prevented by Ni2+ (200 microM), by the GABAB receptor agonist, baclofen (10
      microM) and by NPY (100 nM) or Y2 receptor-selective NPY agonists. Following
      treatment of cells with pertussis toxin, NPY produced only a brief decrease in
      [Ca2+]i fluctuations which rapidly recovered. 3. Perfusion of hippocampal
      neurones with 50 mM K+ produced a large rapid increase in [Ca2+]i. This increase
      was slightly reduced by NPY or by a combination of CNQX and APV. The effects of
      CNQX/APV occluded those of NPY. NPY had no effect on Ba2+ currents measured in
      hippocampal neurones under whole cell voltage-clamp even in the presence of
      intracellular GTP-gamma-S. On the other hand, Ba2+ currents were reduced by both
      Cd2+ (200 microM) and baclofen (10 microM). 4. Current clamp recordings from
      hippocampal neurones demonstrated the occurrence of spontaneous e.p.s.ps and
      action potential firing which were accompanied by increases in [Ca2+]i. This
      spontaneous activity and the accompanying [Ca2+]i signals were prevented by
      application of NPY (100 nM). When hippocampal neurones were induced to fire
      trains of action potentials in the absence of synaptic transmission, these were
      accompanied by an increase in cell soma [Ca2+]j. NPY (100 nM) had no effect on
      these cell soma [Ca2+], signals. NPY (100 nM) also had no effect on inward
      currents generated in hippocampal neurones by micropipette application of
      glutamate (50 microM).5. Thus, NPY is able to abolish excitatory
      neurotransmission in hippocampal cultures through a pertussis toxin-sensitive
      mechanism. However, no effect of NPY on Ca2+ influx into the cell soma of these
      hippocampal neurones could be discerned. These results are consistent with a
      localized presynaptic inhibitory effect of NPY on glutamate release in
      hippocampal neurones in culture.

PMID- 1358390
TI  - Antagonism of synaptic potentials in ventral horn neurones by 6-cyano-7
      nitroquinoxaline-2,3-dione: a study in the rat spinal cord in vitro.
AB  - 1. The rat spinal cord in vitro has been used to assess the effect of 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) on the dorsal root evoked extracellular ventral
      root reflex (DR-VRR) and the intracellular excitatory postsynaptic potential
      (e.p.s.p.) in ventral horn neurones and motoneurones. 2. CNQX (1-5 microM)
      produces a selective and dose-dependent reduction in the amplitude of the
      monosynaptic component of the DR-VRR recorded from lumbar spinal segments. 3.
      With low intensity dorsal root stimulation CNQX selectively attenuates the
      amplitude of the short latency intracellular e.p.s.p. (70% reduction, P < 0.005)
      and its rise-time (75%, P < 0.01) without affecting the half-time to decay. 4.
      When high intensity stimulation is used CNQX significantly attenuates the
      amplitude of the e.p.s.p. (56%, P < 0.005), rise-time (76%, P < 0.01) and
      abolishes the short latency spike. In addition longer latency synaptic components
      are attenuated and the half-time to decay significantly reduced (47%, P < 0.005).
      5. The results with CNQX are compared to D-aminophosphonovalerate and discussed
      in relation to the recruitment of low versus high threshold afferents. The data
      supports an involvement of non-NMDA receptors in transmission through both mono-
      and polysynaptic pathways in the ventral horn.

PMID- 1358391
TI  - Calmidazolium, a calmodulin inhibitor, inhibits endothelium-dependent relaxations
      resistant to nitro-L-arginine in the canine coronary artery.
AB  - 1. The role of calmodulin in endothelium-dependent relaxations in the canine
      coronary artery, was investigated by use of the inhibitor of calmodulin,
      calmidazolium. 2. The endothelium-dependent relaxations to adenosine diphosphate
      (ADP) and nebivolol, a beta-adrenoceptor antagonist, in control solution, and to
      bradykinin in high potassium solution (to inhibit endothelium-dependent
      hyperpolarization), were abolished by nitro-L-arginine (30 microM), an inhibitor
      of nitro oxide-synthase. Calmidazolium (10 microM) did not inhibit these
      relaxations. 3. Calmidazolium did not affect the endothelium-independent
      relaxations to SIN-1, an exogenous donor of nitric oxide (NO). 4. The relaxations
      to bradykinin and to the calcium ionophore A23187 in control solution were
      inhibited to a small extent by calmidazolium (10 microM). 5. Bradykinin and
      A23187 induced relaxations in the presence of nitro-L-arginine (30 microM) that
      were abolished by calmidazolium (10 microM) but not affected by glibenclamide (10
      microM), an inhibitor of ATP-sensitive K+ channels. 6. The endothelium
      independent relaxations to lemakalim, an ATP-sensitive K+ channel opener, were
      not affected by calmidazolium (10 microM) but were inhibited by glibenclamide (10
      microM). 7. These results suggest that calmidazolium does not inhibit the
      endothelium-dependent relaxations due to endothelium-derived NO in the canine
      coronary artery but inhibits either the production of endothelium-derived
      hyperpolarizing factor (EDHF) from endothelial cells or its effects on vascular
      smooth muscle cells. Furthermore these results suggest that EDHF contributes to
      endothelium-dependent relaxations in the canine coronary artery.

PMID- 1358392
TI  - Evidence for a noradrenergic innervation to alpha 1A-adrenoceptors in rat kidney.
AB  - 1. Experiments were undertaken to characterize the alpha 1-adrenoceptor subtype
      mediating vasoconstrictor responses to periarterial noradrenergic nerve
      stimulation (PNS) in the isolated perfused kidney of the rat. 2. Vasoconstrictor
      responses to nerve stimulation were inhibited by prazosin (10 nM), 5-methyl
      urapidil (30 nM), and nitrendipine (1 microM) but were resistant to inhibition by
      chloroethylclonidine (100 microM). 3. 5-Methyl-urapidil (30 nM),
      chloroethylclonidine (100 microM) and nitrendipine (1 microM) did not inhibit the
      neuronal release of tritium from nerves loaded with [3H]-noradrenaline. 4. The
      results suggest that renovascular alpha 1A-adrenoceptors receive a noradrenergic
      innervation and that the innervated receptors are coupled to dihydropyridine
      sensitive calcium channels.

PMID- 1358393
TI  - Effect of histamine and histamine analogues on human isolated myometrial strips.
AB  - 1. The effect of histamine and histamine H1- and H2-receptor agonists on isolated
      myometrium strips of premenopausal women has been examined. The effect of
      acetylcholine was also determined. 2. Histamine, 2-pyridylethylamine, 4
      methylhistamine and acetylcholine, but not dimaprit, produced a concentration
      related contractile response in human isolated myometrial strips. Histamine also
      produced a further contraction in human isolated myometrial strips precontracted
      with KCl (55 mM). 3. The contractile response to histamine was antagonized by the
      histamine H1-receptor antagonist, clemizole (0.1 microM) but was potentiated by
      the histamine H2-receptor antagonist, ranitidine (10 microM). Clemizole (0.1 nM
      to 10 nM) competitively antagonized the contractile effect of 2-pyridylethylamine
      (- log KB = 10.5 +/- 0.5). The concentration-response curve for acetylcholine was
      displaced to the right by atropine 0.1 microM. 4. Atropine (0.1 microM),
      propranolol (0.1 microM), prazosin (0.1 microM) and indomethacin (1 microM)
      failed to modify the contractile response to histamine. 5. In human isolated
      myometrial strips precontracted with KCl (55 mM), clemizole at 1 microM
      completely abolished the contractile response to histamine and revealed a
      concentration-dependent relaxation. Dimaprit alone and 4-methylhistamine (in the
      presence of clemizole), produced concentration-related relaxation with a
      magnitude similar to that in response to histamine. The relaxant response to
      dimaprit was antagonized by ranitidine. 6. It is concluded that human isolated
      uterine strips possess histamine H1- and H2-receptors: the former mediating
      contraction and the latter relaxation. The predominant response to histamine in
      this tissue is contraction.

PMID- 1358394
TI  - Cannabis and psychotic illness.
AB  - In-patients with psychotic symptoms and cannabis-positive urine analysis were
      assessed by PSE within one week of admission and again at one and six months.
      Concurrently admitted psychotic patients with drug-free urine analysis were
      controls. At one week the two groups differed significantly on only five PSE
      items: changed perception, thought insertion, non-verbal auditory hallucinations,
      delusions of control, and delusions of grandiose ability. One item (delayed
      sleep) differed at one month, and none at six months. The symptom cluster at one
      week is consistent with acute cannabis intoxication. Subjects and controls were
      mostly single, poorly educated, unemployed people with histories of psychotic
      disorders, and given major tranquillisers on admission. Compared with controls,
      subjects were younger, less likely to have psychiatric histories, more often
      male, Afro-Caribbeans with a history of convictions and compulsory admissions.
      The commonest diagnosis was schizophrenia. Use of the label 'cannabis-induced
      psychosis' may obscure a diagnosis of paranoid schizophrenia. A short-lived
      psychotic episode does occur in clear consciousness after cannabis intoxication,
      but chronic cannabis-induced psychosis was not found.

PMID- 1358395
TI  - The use of image habituation training with post-traumatic stress disorders.
AB  - An exposure treatment for patients suffering from post-traumatic stress disorder
      (PTSD) is described. Image habituation training (IHT) involves the patient in
      generating verbal descriptions of the traumatic event and recording these onto an
      audiotape. After the initial training session with the therapist, homework
      sessions of self-directed exposure in which the patient visualised the described
      event in response to listening to the audiotape were carried out. Of ten
      consecutive patients who received this treatment, six improved considerably after
      ten homework sessions, two showed moderate improvements, and two showed minimal
      improvement on a range of outcome measures. There were significant decreases in
      anxiety between and within homework sessions, suggesting that habituation did
      occur and was responsible for improvement. Treatment gains were maintained at six
      month follow-up.

PMID- 1358396
TI  - Benzodiazepines with ECT.

PMID- 1358397
TI  - Non-surgical management of the acute variceal bleed.

PMID- 1358398
TI  - Control of simultaneous movements distinguishes depressive motor retardation from
      Parkinson's disease and neuroleptic parkinsonism.
AB  - Patients with depressive motor retardation, neuroleptic induced parkinsonism or
      Parkinson's disease were tested on movement tasks requiring control of
      simultaneous movements. This was in order to determine whether these three groups
      of patients, who all show slowing of movements, also share the distinctive
      impairment of simultaneous movement control that is observed in Parkinson's
      disease. Though all three patient groups showed equivalent slowing on the motor
      tasks that were studied, the patterns of impairment were different. Only the
      patients with parkinsonism, either neuroleptic induced or from Parkinson's
      disease, showed additional slowing of a rapid ballistic elbow flexion movement
      when it was performed simultaneously with a rapid squeeze of the ipsilateral
      hand. Only patients with parkinsonism showed a significant increase in dual task
      interference on a bimanual bead and tapper task, compared with controls. The bead
      and tapper interference in patients with depressive motor retardation was between
      that of controls and parkinsonism. Having a bimanual skill had a large effect on
      the subjects' dual task interference on this task. The measures of dual task
      interference for the two tasks did not correlate with one another; difficulty
      running simultaneous motor programs does therefore not explain the interference
      that is observed when tapping is performed while the other hand simultaneously
      performs a dextrous motor task. Only patients with parkinsonism showed increased
      fatigue on the tapping task. The patients with depressive motor retardation did
      have elevated scores on a clinical rating of parkinsonism. Nevertheless there are
      clearly defined differences between the movement disorder observed in patients
      with depression, and that observed in in parkinsonism. The patterns of
      impairments in patients with neuroleptic parkinsonism were very similar to those
      of Parkinson's disease.

PMID- 1358399
TI  - Characterization of superior cervical ganglion neurons that project to the
      submandibular glands, the eyes, and the pineal gland in rats.
AB  - These studies sought to determine whether the cell bodies of rat superior
      cervical ganglion neurons projecting to three very different target organs differ
      in terms of their size, number, location within the ganglion and/or neuropeptide
      content, and whether these features are altered in response to neonatal
      deafferentiation of the ganglion. A series of retrograde tracer,
      immunocytochemical, and double-labeling studies revealed differences in the size,
      number, location and neuropeptide content of superior cervical ganglion neurons
      that project to the submandibular salivary glands, eyes, or pineal gland. The
      mean areas of the cell bodies of neurons projecting to the submandibular gland
      are largest, those projecting to the eye are smallest, and those projecting to
      the pineal are intermediate in size. Submandibular gland projecting neurons are
      found throughout the ganglion, while the eye and pineal projecting populations
      are localized to the rostral quadrants. The different subpopulations of target
      organ specific superior cervical ganglion neurons are heterogeneous in their
      content of vasoactive intestinal peptide-, neuropeptide Y- and somatostatin-like
      immunoreactivity. A greater percentage of submandibular gland than of pineal
      projecting neurons display vasoactive intestinal peptide-like immunoreactivity,
      but there are no differences in the percentage of neurons displaying neuropeptide
      Y- or somatostatin-like immunoreactivity between the target organ specific
      groups. Neonatal deafferentiation does not result in changes in the size, number
      or distribution of target organ specific neurons, or in the percentage of
      immunoreactive neurons in these populations. In conclusion, these studies provide
      evidence that the size and distribution of neurons and percentage of peptide
      containing neurons in the superior cervical ganglion is related to the target
      organ innervated, but provides no evidence of exclusive target organ-peptide
      relationships.

PMID- 1358400
TI  - NMDA-receptor mediated electrical epileptogenesis in the organotypic culture of
      rat hippocampus.
AB  - Extracellular field recordings were made in CA1 in the hippocampal explant
      cultures in oxygenated artificial cerebrospinal fluid. Schaffer collaterals were
      stimulated with 1-s trains of 60 Hz pulses every 10 min. Seizures were reliably
      elicited with progressive lengthening over 1-2 h. D-APV, an N-methyl-D-aspartate
      (NMDA) antagonist, stereoselectively blocked the development of seizures. Thus we
      have demonstrated that in vitro epileptogenesis occurs in hippocampal explant
      cultures through NMDA receptor mediated mechanisms.

PMID- 1358401
TI  - Projection from the ventrolateral medullary neurons containing tyrosine
      hydroxylase to the central amygdaloid nucleus in the rat.
AB  - By using a double-labeling produce of retrograde horseradish peroxidase (HRP)
      tracing and the immunocytochemical localization of tyrosine hydroxylase (TH), the
      present study ascertained that the axonal fibers of catecholaminergic neurons in
      the caudal ventrolateral medulla projected to the central amygdaloid nucleus in
      the rat. The majority of double-labeled cells were observed primarily around the
      level of the obex. 92% of HRP retrogradely labeled cells contained TH-like
      immunoreactive (TH-IR), but only 31% of TH-IR cells was labeled with HRP.

PMID- 1358402
TI  - Glutamate neurotoxicity in the developing rat cochlea is antagonized by kynurenic
      acid and MK-801.
AB  - Glutamate (Glu) is neurotoxic in the neonatal rat cochlea, producing hearing
      impairment which is largely due to the death of spiral ganglion cells, whereas
      the receptor hair cells are spared. Dendritic processes of the spiral ganglion
      are postsynaptic to the primary afferent synapse of the auditory system. The
      experiments reported here were designed to test whether this apparent
      excitotoxicity can be blocked by Glu antagonists. The broad-spectrum antagonist
      kynurenic acid (KYNA) was coadministered with Glu initially to determine whether
      the high-frequency hearing deficit caused by Glu may be mediated by excitatory
      amino acid receptors. Subsequently, the N-methyl-D-aspartate (NMDA)-specific
      receptor blocker MK-801 was used to test whether NMDA receptors may be involved
      in the effect. Both antagonists partially blocked the high-frequency hearing
      impairment caused by Glu. The blocker-alone control groups exhibited mid
      frequency effects of unknown origin. The significant antagonism of Glu-induced
      impairment is consistent with the hypothesis that Glu or a similar excitatory
      amino acid is an important afferent transmitter in the cochlea.

PMID- 1358403
TI  - Further evidence for differential affinity states of the serotonin1A receptor in
      rat hippocampus.
AB  - The binding profile of [3H]8-hydroxy-2-(di-N-propylamino)-tetralin ([3H]8-OH
      DPAT) to serotonin1A (5-HT1A) sites in rat hippocampal, frontocortical and
      striatal membranes has been compared. In these regions, [3H]8-OH-DPAT labels both
      a high and a low-affinity binding site; the affinity values for each of the two
      sites are comparable in the different brain regions, but have different maximal
      capacity. By modifying the experimental conditions in a series of hippocampal
      membrane preparations, reciprocal changes in the proportion of the two sites were
      observed suggesting that they represent, at least in this region, different
      conformations or affinity states of a single receptor protein. In contrast to the
      lower affinity state, it appears that the high-affinity state is stabilized by
      coupling with a G-protein. Evidence supporting this statement is provided by
      addition of the guanine nucleotide Gpp(NH)p, breakage of labile disulfide bonds
      using N-ethylmaleimide and increasing membrane rigidity with ascorbate-induced
      lipid peroxidation, conditions which all reduced the density of receptors in the
      high-affinity state. Moreover, the high-affinity state appears to be stabilized
      at the expense of the lower affinity state in the presence of Mn2+. On the other
      hand, a complete shift to the low-affinity binding state was observed after a 24
      h in vivo treatment with inhibitors of monoamine oxidase A (phenelzine or
      clorgyline) but not of monoamine oxidase B (deprenyl). This disappearance of the
      high-affinity state with a concomitant increase in the binding capacity of the
      low-affinity state was reproduced by inhibiting monoamine oxidase A in vitro, as
      well as by reducing preincubation washout periods. Also, competitors of the [3H]8
      OH-DPAT binding site, such as serotonin and unlabelled 8-OH-DPAT, display two
      affinity states while others like (+/-)-propranolol, tryptamine and spiperone
      recognize a single affinity component. These results suggest that the 5-HT1A
      binding site may exhibit at least two different affinity states depending upon
      its microenvironment and the intrinsic activity of the ligand used.

PMID- 1358404
TI  - Reactive proliferation of astrocytes studied by immunohistochemistry for
      proliferating cell nuclear antigen.
AB  - Astrocyte proliferation in the stab-wounded cerebral cortex of mice was studied
      using double immunohistochemistry for proliferating cell nuclear antigen (PCNA)
      and glial fibrillary acidic protein (GFAP). The number of GFAP-positive
      astrocytes increased markedly from day 0.5 to day 3 after stab wounding. Some
      GFAP-positive astrocytes in the immediate vicinity of the wound were found to be
      positive for PCNA. However, the maximum number of these double positive
      astrocytes was only 5-6% of the number of GFAP-positive astrocytes. This maximum
      value was observed on days 2.5 and 3. The present study revealed that astrocytes
      are able to reactively express PCNA, an intrinsic marker of DNA replication. On
      the other hand, it is suggested that the proliferation of astrocytes in the
      wounded cerebral cortex is limited, in contrast with their marked reactive up
      regulation of GFAP.

PMID- 1358405
TI  - Flunarizine induces a transient loss of tyrosine hydroxylase immunoreactivity in
      nigrostriatal neurons.
AB  - Neurotoxic effects of flunarizine (Fz), a selective calcium channel blocker, on
      the nigrostriatal dopamine system was investigated. Systemic injections of Fz to
      mice resulted in a transient loss of tyrosine hydroxylase (TH) immunoreactive
      nigrostriatal neurons without cell loss. TH immunoreactivity in these neurons was
      greatly reduced as rapidly as one day after drug administration (regardless of
      dosage used) and thereafter recovered in both dose- and time-dependent manners.
      Such a novel neurotoxic action of Fz may constitute a morphological substrate for
      reversible drug-induced parkinsonian signs described in recent clinical case
      reports.

PMID- 1358406
TI  - Specificity of 192 IgG-saporin for NGF receptor-positive cholinergic basal
      forebrain neurons in the rat.
AB  - A monoclonal antibody to the rat nerve growth factor (NGF) receptor, 192 IgG,
      accumulates bilaterally and specifically in cholinergic basal forebrain (CBF)
      cells following intraventricular injection. An immunotoxin composed of 192 IgG
      linked to saporin (192 IgG-saporin) has been shown to destroy cholinergic neurons
      in the basal forebrain. We sought to determine if intraventricular 192 IgG
      saporin affected choline acetyltransferase (ChAT) enzyme activity in the CBF
      terminal projection fields. ChAT assays from 192 IgG-saporin-treated animals
      showed significant time-dependent decreases in ChAT activity in the neocortex,
      olfactory bulb and hippocampus, compared to PBS- or OKT1-saporin-injected
      controls. ChAT and tyrosine hydroxylase activity in the striatum was always
      unchanged by 192 IgG-saporin. ChAT immunohistochemistry was confirmative of major
      cell loss in the CBF, while other cholinergic nuclei appeared unremarkable. The
      data provide further evidence of the selectivity of 192 IgG-saporin in abolishing
      cholinergic, NGF receptor-positive CNS neurons.

PMID- 1358407
TI  - Analgesic actions of dynorphin A(1-13) antiserum in the rat brain stem.
AB  - This study was performed to evaluate the effects of dynorphin A(1-3) antiserum
      when microinjected into an active hyperalgesic region within the rat brain stem.
      When administered within the dorsal posterior mesencephalic tegmentum (DPMT) of
      intact conscious rats, dynorphin A(1-13) antiserum produced rapid onset and
      persistent prolongation of a low intensity thermally evoked tail avoidance
      response (LITETAR). These analgesic actions of the dynorphin A(1-13) antiserum
      appeared to be dose dependent. These studies support previous hypotheses about
      the existence of tonically active brain stem opioid hyperalgesic process.
      Further, the results provide indirect evidence for a potential role of brain stem
      dynorphin(s) in facilitating pain.

PMID- 1358408
TI  - Afferent and sympathetic innervation of the dome and the base of the urinary
      bladder of the female rat.
AB  - The afferent and sympathetic innervation of different regions of the urinary
      bladder (bladder dome vs. bladder base) was examined in the female rat using
      simultaneous injections of two fluorescent tracers. Retrogradely labeled cells
      were found in the dorsal root ganglia (DRG; L1-L3 and L6-S1), the sympathetic
      chain (SC; T12-L6), the inferior mesenteric ganglia (IMG) and the major pelvic
      ganglia (MPG). There were very few double-labeled cells, indicating that the dome
      and the base of the bladder receive innervation (afferent or sympathetic) from
      separate and distinct neuronal populations. Most of the sympathetic innervation
      of the bladder arose from the SC (dome: 77%; base: 89%) and it was carried
      equally by the hypogastric and pelvic nerves. The distributions of SC
      postganglionic neurons innervating the dome and the base of the bladder were very
      similar. In contrast, the contribution of IMG neurons was almost entirely
      restricted to the dome of the bladder (22%), with less than 1% innervating the
      base. Tyrosine hydroxylase-immunoreactive (TH) neurons in the MPG displayed a
      strong sexual dimorphism. Many TH neurons were found in the male MPG, but very
      few in the female MPG. In the female, these TH neurons projected almost
      exclusively to the bladder base of the female rat and were responsible for 10% of
      the sympathetic innervation of the base. Less than 1% innervated the dome.
      Therefore, prevertebral ganglia (IMG and MPG) show a strong regional selectivity
      in the innervation of the bladder of the female rat. The possible functional
      implications of this organization are discussed.

PMID- 1358409
TI  - Antitumor activity of tiazofurin in human colon carcinoma HT-29.
AB  - Tiazofurin is effective in treating end-stage leukemic patients (Tricot et al.,
      Cancer Res 49:3696-3701, 1989). In sensitive tumors, the active metabolite of
      tiazofurin, TAD, potently inhibits IMP dehydrogenase activity, resulting in
      reduced guanylate pools. To elucidate tiazofurin activity in human solid tumors,
      we examined its activity in human colon carcinoma HT-29. Tiazofurin exhibited an
      LC50 of 35 microM in cultured HT-29 cells. Incubation of HT-29 cells with 100
      microM tiazofurin for 2 h resulted in TAD formation (9.3 nmol/g cells) and in a
      64% decrease in GTP pools. For biochemical and chemotherapy studies, athymic nude
      mice were transplanted s.c. with HT-29 cells. Twenty-four days later, mice were
      injected i.p. with tiazofurin (500 mg/kg); 6 h later, tumors were removed and
      analyzed. These tumors formed 17 nmol/g of TAD with decreased GTP pools (56%). To
      study oncolytic activity, transplanted mice were treated 24 h later with
      tiazofurin (500 mg/kg, once a day for 10 days). To examine the effectiveness of
      tiazofurin in established tumors, the drug was administered to mice 14 days after
      tumor implantation (500 mg/kg, once a day for 5 days, course repeated 4 times
      with a 10-day rest). Both treatment schedules resulted in significant antitumor
      activity. This study illustrates the potential usefulness of tiazofurin in
      treating human colon carcinoma.

PMID- 1358410
TI  - Clinical significance of erbB-2 (HER-2/neu) protein.
AB  - erbB-2 protein is believed to be a cell membrane receptor for the recently
      identified ligand gp30. When overexpressed, erbB-2 is an indicator of poor
      prognosis in adenocarcinomas of breast, stomach, lung, and endometrium. Even more
      important, clinical data suggest that erbB-2 overexpression may be an indicator
      of poor response to at least some commonly used adjuvant regimens. However, there
      is preliminary evidence that these tumors might respond as well to doxorubicin
      regimen as do erbB-2 negative tumors, at least in gastric cancer. The efficacy of
      doxorubicin-containing regimen in the treatment of tumors with erbB-2
      overexpression needs to be explored further by retrospective analysis of finished
      clinical trials. Combination of chemotherapeutics with reagents that block erbB-2
      signal transduction pathway may be another effective approach.

PMID- 1358411
TI  - Leukocyte integrin activation.

PMID- 1358412
TI  - [Programmed death (apoptosis) of T CD4 lymphocytes and AIDS pathogenesis].
AB  - A major characteristic of human immunodeficiency virus (HIV) infection is
      progressive decline in T CD4+ lymphocytes. Ten years after infection, on average,
      this cell subpopulation disappears and AIDS develops. In the asymptotic phase T
      CD4+ lymphocytes no longer respond, in vitro or in vivo, to certain memory
      antigens constrained by the class II histocompatibility complex, or in vitro to
      polyclonal activators like pokeweed mitogen. They retain, however, some
      proliferative response activity and constitute only a small proportion of the T
      CD4+ population. Indirect mechanisms of depletion are therefore sought. We have
      proposed a hypothesis for a single mechanism: a programmed death process,
      apoptosis, reactivated in mature T CD4+ lymphocytes of seropositives. Unlike
      necrosis, apoptosis has a role in embryogenesis, in the adult in certain cell
      populations and, in immature thymocytes, in T lymphocyte selection and
      establishment of self-tolerance. T CD4+ lymphocytes of infected subjects lose
      their ability to proliferate in vitro, as they undergo a form of suicide in
      response to certain stimuli. In vivo T CD4+ cell activation induced by various
      infectious agents, including HIV, progressively reduces the subpopulation,
      independently of the virus' cytopathogenic effect. Tests were performed that
      explored the T CD4+ lymphocyte response to super-antigens, which mimic and
      amplify the effect of memory antigens by way of CMH II molecules of Ag-presenting
      cells and certain nu beta chains of the alpha beta receptor for the Ag which are
      expressed by a third of human mature T CD4+ lymphocytes.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1358413
TI  - [Are embryonic forms of NCAM homeobox receptors?].
AB  - In a previous study we demonstrated that the homeobox peptide pAntp was able to
      penetrate into rat embryonic neurons in culture thus provoking their
      morphological differentiation [1]. In the present work we have started to analyse
      the process of penetration of the homeobox peptide. As illustrated in Figure 1
      pAntp migrating as a homogeneous 7 kDa band could be recovered in the nuclear
      fraction 2 hrs. only after its addition to cultured embryonic neurons (lane 2).
      Penetration and nuclear targeting were quantitatively blocked by preincubating
      pAntp with its cognate recognition sequence present in the promoter of Hox-1.3
      (lane 3) or by incubating the cells with an antibody directed against the NCAM
      specific alpha 2-8 polysialic acid (lane 4). Similar inhibitions were observed
      when the peptide was incubated with double stranded DNA or added to cells
      deprived of alpha 2-8 polysialic acid by EndoN treatment (not shown). As
      illustrated in Figure 2, the strong pAntp-induced neurite growth was antagonized
      when pAntp internalization was prevented by the EndoN removal of PSA. This effect
      of EndoN was not due to the enzyme itself since morphological differentiation was
      not inhibited if EndoN was added after pAntp penetration (Fig. 2B). Polysialic
      acid is composed of long chains of neuraminic acids, each pyranose ring carrying
      a negatively charged carboxylic group linked to carbon in position 1. NMR studies
      of the molecule in solution have demonstrated that the alpha 2-8 link between
      each pyranose ring allows specific and stable helical conformation [2].(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1358414
TI  - Paradoxical sleep deprivation increases glutamine synthetase in rat brain.
AB  - The modifications of glutamine synthetase (GS) level, an enzyme mainly located in
      astrocytes, were investigated in rat after paradoxical sleep deprivation and
      during recovery. An immunotitration method was used to evaluate the relative
      level of GS in brain tissue. At the end of a 24 hrs. paradoxical sleep
      deprivation, a significant increase in GS level was observed both in the
      frontoparietal cortex and the locus coeruleus area. 4 hrs. later, during
      recovery, the GS level returned to control level in the cortex but was lower in
      the locus coeruleus area.

PMID- 1358415
TI  - Viruses as precipitants of asthma symptoms. II. Physiology and mechanisms.
AB  - The upper and lower airways have complimentary roles in the ultimate object of
      supplying the body with oxygen whilst removing waste products of metabolism.
      Pathology in one area may trigger a response in another, the physiology of which,
      in the case of virus-induced asthma exacerbations remains poorly characterized.
      Viral infection of the upper airways by common cold viruses frequently triggers a
      response in the lower airways leading to prolonged morbidity, especially in
      subjects with significant pre-existing airway disease. The induction or
      amplification of BHR may be an important mechanism whereby asthmatic symptoms are
      produced although the cellular and tissue events or reflex mechanisms activated
      by viral illnesses and underlying BHR changes are poorly defined and may be
      dependent on the type and the severity of infection. Children and asthmatics tend
      to develop frequent colds setting in motion a sequence of events culminating in
      airway obstruction and symptoms of wheezing, coughing and chest tightness. This
      may reflect independent inflammatory changes caused by a simply additive effect
      of viral damage to the mucosa superimposed upon pre-existing allergic
      inflammation (Fig. 1). Few if any symptoms will develop in normal subjects with a
      mild cold whereas significant symptoms may ensue if the cold is severe and
      induces marked lower airway swelling, secretions and smooth muscle contraction;
      pathology to which children who have small calibre airways may be particularly
      susceptible. In asthmatics even a mild cold frequently induces exacerbation of
      symptoms, while serious life-threatening asthma attacks may occur associated with
      a severe cold. Some studies have suggested that this effect is not only additive
      but also synergistic and brought about by release of the mediators already
      present in increased quantities, the induction of IgE synthesis, or by the
      potentiation of neural and epithelial damage. The combined effect of both asthma
      and viruses may thus be amplified and result in a sustained and refractory period
      of airway obstruction, severe symptoms and unstable asthma. As most hospital
      admissions for asthma occur over the winter months and soon after the start of
      the school terms [115], spread of viruses through the community to susceptible
      individuals may be the single most important cause of sustained exacerbations of
      asthma. Definition of the pathological and physiological mechanisms involved will
      lead to better understanding and may thus provide a basis for prevention and the
      development of effective forms of treatment for virus-induced asthma.

PMID- 1358416
TI  - Genetics and regulation of the human immune response. Report on a symposium held
      at Ringberg Castle, Rottach-Egern a. Tegernsee.

PMID- 1358418
TI  - Abstracts from the 3rd Symposium of the Spanish Society of Bone and Mineral
      Research (SEIOMM). Oviedo, Spain, 25-27 September 1991.

PMID- 1358417
TI  - An osteonectin-like protein in the matrix of cultured osteogenic cell-line MC3T3
      E1, which is associated with calcification.
AB  - Time-dependent changes of the [3H]-proline-labeled noncollagenous proteins
      synthesized by the osteogenic cell-line MC3T3-E1 were analyzed over a range
      starting from cell confluency to 13 days after confluency during which time cells
      formed a bone-like structure. It was found that the 40 kDa protein on SDS
      polyacrylamide gel (SDS-PAGE) remarkably increased in the cell-matrix layer at
      about 9 days after cell confluence, just before calcification. This protein was
      highly purified and was found to contain high amounts of glutamic acid, glycine,
      and serine. An internal amino acid sequence of this protein was revealed to be K
      X-M-A-P-E-E-X-P, which showed homology with the sequence of the EF-hand domain in
      osteonectin/SPARC (secreted protein, acidic, and rich in cysteine). This protein
      co-migrated with collagen in gel filtration, and ion-exchange chromatography.
      Furthermore, it showed high affinity to type I collagen.

PMID- 1358419
TI  - Proceedings from a symposium of basic research on ipriflavone (Osten). Yokohama,
      Japan. January 18, 1992.

PMID- 1358420
TI  - Specific restriction fragment length polymorphism in liver mitochondrial DNA of
      the Chinese.
AB  - By use of restriction fragment length polymorphism analysis, we examined the
      liver mitochondrial DNA amplified by polymerase chain reaction from 60 Chinese
      subjects of 31 to 78 years of age. We found nine specific mtDNA polymorphisms
      that had never been reported before. Eleven subjects had an Alu I polymorphic
      site in the subunit 2 gene of NADH dehydrogenase, five had a Hae III polymorphic
      site in the cytochrome oxidase subunit 2 gene, and five had a Hinf I polymorphic
      site in the subunit 3 gene of cytochrome oxidase. No polymorphic site was found
      in the structural genes coding for subunits 1, 3, 4, 4L and 6 of NADH
      dehydrogenase, cytochrome b, and subunit 8 of ATP synthase. Detailed analysis of
      the RFLP data did not show age-dependent mtDNA polymorphisms. In addition, the
      analysis of the restriction patterns of all the mtDNAs revealed 12 mtDNA
      haplotypes in all the Chinese subjects examined. Among them, type 1 mtDNA was
      found to be the most predominant and comprised 63.3% of the total study subjects.
      The restriction patterns of type 1 mtDNA generated by all restriction enzymes
      were identical to those deduced from the Cambridge sequence of human mtDNA. About
      8.3% of the subjects exhibited type 2 mtDNA, and 5% had types 3, 5 and 8 mtDNA,
      respectively. Each of the rest seven mtDNA types comprised about 2% of the
      samples. Moreover, type 1 mtDNA was found in the platelets of three white
      Americans. These findings suggest that type 2 to type 12 mtDNAs have come into
      existence through the generation or loss of specific polymorphic restriction
      sites in the mtDNA of the Chinese.

PMID- 1358421
TI  - Yohimbine-precipitated clonidine withdrawal: an experimental model of the
      antihypertensive drug withdrawal syndrome.
AB  - In this study, a model of the clonidine withdrawal syndrome in normotensive rats
      was used to investigate the mechanisms and sites of the cardiovascular responses
      associated with this withdrawal. Clonidine (400 micrograms.kg-1.day-1), an alpha
      2-adrenergic receptor agonist, was administered to rats via indwelling osmotic
      minipumps for 7 days. Withdrawal was precipitated by an intravenous injection of
      the alpha 2-adrenergic receptor antagonist yohimbine under alpha-chloralose
      anaesthesia, and the blood pressure and heart rate responses were recorded.
      Yohimbine (0.25, 0.50, and 1.0 mg/kg i.v.) in clonidine-treated rats provoked an
      immediate rise in blood pressure and heart rate. Similar injections in saline
      treated rats produced slight hypotension and modestly increased the heart rate.
      Intracerebroventricular (i.c.v.) yohimbine injection (30 or 120 micrograms/kg in
      10 microL volume) failed to elicit signs of withdrawal in clonidine-treated
      animals, but a subsequent intravenous injection of yohimbine (0.5 mg/kg) provoked
      brisk signs of withdrawal. hexamethonium (2 mg/kg) pretreatment did not abolish
      the increase in the heart rate, but it delayed the blood pressure increase.
      Pretreatment with atropine sulfate (1 mg/kg) did not block the yohimbine-induced
      increase in heart rate or blood pressure. This study demonstrates that yohimbine
      can effectively produce cardiovascular signs of withdrawal in rats chronically
      exposed to clonidine. The lack of i.c.v. yohimbine suggests that the antagonist
      precipitated withdrawal may not have a central origin.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1358422
TI  - A comparison of the effects of acute versus chronic administration of
      phenoxybenzamine on pressor responses elicited by the selective alpha 1
      adrenoceptor agonist cirazoline in the pithed rat preparation.
AB  - The effects of nifedipine on the pressor responses to cirazoline were examined in
      the pithed rat preparation that had received either acute or chronic
      phenoxybenzamine treatment. Phenoxybenzamine was administered, i.v., to conscious
      rats, either acutely at 0.01, 0.03, and 0.1 mg/kg, 60 min prior to the
      commencement of the experiments or chronically at 0.1, 0.3, and 1.0 mg/kg, once
      daily for 7 days. Nifedipine was administered i.a. (1.0 mg/kg) after the animals
      had been pithed. The acute or chronic administration of phenoxybenzamine alone
      displaced the dose-response curve to cirazoline to the right in a dose-dependent
      manner, while reducing the slope function and maximum response to the agonist.
      The combined effects of acute phenoxybenzamine and nifedipine produced an
      additive inhibitory effect on the pressor response elicited by cirazoline, which
      was most apparent following the removal of receptor reserve by acute
      phenoxybenzamine. The inhibitory effects of nifedipine and chronically
      administered phenoxybenzamine were additive at the lower administered doses of
      the alkylating agent but, in contrast with the effects of acute phenoxybenzamine,
      the enhanced inhibitory effects of nifedipine were reduced following the removal
      of receptor reserve. These results indicate that the chronic administration of
      phenoxybenzamine reduces the additive inhibitory effects of nifedipine and
      phenoxybenzamine that were observed following the acute administration of
      phenoxybenzamine.

PMID- 1358423
TI  - Suppression of spreading depression of Leao in neocortex by an N-methyl-D
      aspartate receptor antagonist.
AB  - Spreading depression has been implicated in the pathophysiology of a number of
      diseases such as migraine, stroke and epilepsy. The characteristics of this
      phenomenon were explored in neocortex of anesthetized rats. Spreading depression
      was produced in 10 of 15 animals using mechanical, electrical and chemical
      stimulation. Mean amplitude of the DC shift was -9.3 mV, mean duration at any one
      electrode 65 sec and rate of spread 2-5 mm/min. Spreading depression was
      facilitated by focal interictal spike activity induced by penicillin and
      completely blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist, DL-2
      aminophosphonovaleric acid (APV), providing further evidence that excitatory
      amino acid neurotransmission is a critical element in the development or
      propagation of the phenomenon.

PMID- 1358424
TI  - Health Promotion Research Methods: Expanding the Repertoire. Conference. Toronto,
      Ontario, 30 November-2 December 1990.

PMID- 1358425
TI  - Health promotion research methods: expanding the repertoire.

PMID- 1358426
TI  - Different sensitivities of human esophageal cancer cells to multiple anti-cancer
      agents and related mechanisms.
AB  - Mechanisms responsible for drug resistance in human esophageal cancer cell lines
      were investigated. Three cell lines established from human esophageal carcinoma
      (TE-1, SH-1, and TH) showed different sensitivities to vindesine, vincristine,
      cisplatin (CDDP), etoposide (VP-16), and pepleomycin. Both SH-1 and TH cell lines
      were twofold to sevenfold more resistant to pepleomycin, vindesine, and
      vincristine than TE-1 was. SH-1 showed twofold more resistance to CDDP than
      either TE-1 or TH did, and TH and TE-1 showed a 3-fold or 1.5-fold more
      resistance, respectively, to VP-16 than SH-1 did. The accumulation of tritiated
      vincristine in SH-1 and TH was approximately 50% that in TE-1. Two multidrug
      resistance reversal agents, cepharanthine and a synthetic dihydropyridine
      analogue (NK-252; Nikken Chemicals, Saitama, Japan), potentiated the cytocidal
      actions of vindesine against SH-1, TH, and TE-1 cells, with no apparent
      expression of P-glycoprotein in the three cell lines. The glutathione S
      transferase pi gene was expressed in all three cell lines. DNA topoisomerase II
      levels were lowest in TE-1, followed by SH-1 and TH, although the accumulation of
      tritiated VP-16 was less in both TH and SH-1 than in TE-1. Differential
      sensitivities to anti-cancer drugs appear to be mediated through pleiotropic
      mechanisms.

PMID- 1358427
TI  - An immunohistologic evaluation of C-erbB-2 gene product in patients with urinary
      bladder carcinoma.
AB  - BACKGROUND: Amplification or overexpression of the c-erbB-2 gene have been
      reported to correlate with poor patient prognosis in human breast, gastric, and
      ovarian cancer. Recently, the c-erbB-2 gene product was found to be expressed
      frequently in the urinary bladder carcinoma. In the current study, the presence
      of the c-erbB-2 gene product in urinary bladder carcinomas was compared with
      patient outcome to evaluate whether c-erbB-2 gene product could identify a subset
      of patients who are destined to have a poor prognosis. METHODS: Immunohistologic
      study of the c-erbB-2 gene product was done in formaldehyde-fixed paraffin
      embedded tissue specimens obtained from 88 transitional cell carcinomas of the
      human urinary bladder. Eighty-three patients who underwent complete tumor
      resection by total cystoprostatectomy (30 patients) or by bladder-preserving
      operations such as transurethral surgery (50 patients) or partial cystectomy (3
      patients) entered a follow-up study. The other five patients did not enter the
      follow-up study because of lost follow-up (2 patients) or distant metastasis at
      the time of surgery. RESULTS: The c-erbB-2 gene product was expressed in 23 of 88
      patients (26%), showing an increase in the expression rate corresponding to the
      advancement of tumor grade (P < 0.05) and tumor stage (P < 0.2). The 5-year
      disease-free survival rate was 48.5% for patients with c-erbB-2 negative tumors
      versus 9.7% for those with c-erbB-2 positive tumors (P < 0.01). The 5-year
      actuarial survival rate was 65.5% for patients with c-erbB-2 negative tumors
      versus 41.8% for those with c-erbB-2 positive tumors (P < 0.05). Multivariate
      analysis using Cox regression model showed that the c-erbB-2 gene product tissue
      status was a significant prognostic factor independent of grade and stage of the
      tumor. CONCLUSIONS: The results suggest that the c-erbB-2 gene product could be a
      tumor marker to identify a malignant subgroup in bladder carcinomas.

PMID- 1358428
TI  - A kindred with multiple endocrine neoplasia type 2A associated with pruritic skin
      lesions.
AB  - BACKGROUND: A kindred affected by multiple endocrine neoplasia type 2A (MEN 2A),
      associated with symmetric, bilateral, scapular pruritic skin lesions (PSL), is
      reported. METHODS: There were 21 members, including the propositus, in four
      generations. Screening of 10 family members showed a palpable thyroid tumor in 1
      and positive results for a pentagastrin test in 7 others. Two of these patients
      had surgically confirmed pheochromocytoma. Two others had a biochemical diagnosis
      of pheochromocytoma but did not have surgery. RESULTS: Medullary thyroid
      carcinoma was confirmed in five patients and nodular C-cell hyperplasia in
      another. In five affected adults, PSL were observed in the interscapular region,
      crossing the midline in some. These lesions were characterized by hyperkeratosis
      and hyperpigmentation. In all the patients, the pruritus had been present long
      before the clinical or biochemical diagnosis. Skin biopsies were performed in two
      of these patients. No amyloid deposits were found (Congo red stain and electron
      microscopic examination were used). Two children (14 and 6 years old) in the
      fourth generation complained of scapular pruritus, although skin lesions were not
      apparent. CONCLUSIONS: Localized PSL must be sought when screening for MEN 2A.

PMID- 1358429
TI  - Cytogenetics of multiple endocrine neoplasia syndrome. II. Chromosome
      abnormalities in an insulinoma and a glucagonoma from two subjects with MEN1.
AB  - Cytogenetic analysis of two pancreatic islet tumors, an insulinoma and a
      glucagonoma was ascertained in two subjects with multiple endocrine neoplasia
      type 1 (MEN1). The insulinoma had a modal peak at 84 chromosomes. Most cells were
      pseudotetraploid, and in all cells the normal chromosomes were represented in
      varied numbers, i.e., from 1 to 7 copies. The tumor had 5 characteristic and
      consistent marker chromosomes which were identified as deletions of chromosomes
      1, 2, 7, 16, and 17. All metaphases had several double minute chromosomes (dmin)
      of variable size and possible intermediate structures between dmin and
      homogeneously staining chromosomal regions. The glucagonoma had a nearly equal
      proportion of normal metaphases and metaphases with structural and numerical
      abnormalities with no consistent trend.

PMID- 1358430
TI  - The 3rd European Workshop on Cytogenetics and Molecular Genetics of Human Solid
      Tumors. Porto-Espinho, Portugal, April 26-29, 1992. Abstracts.

PMID- 1358431
TI  - Reduced intracellular drug accumulation in the absence of P-glycoprotein (mdr1)
      overexpression in mitoxantrone-resistant human MCF-7 breast cancer cells.
AB  - A mitoxantrone-resistant human MCF-7 breast cancer subline (MCF/MX) which is
      approximately 4000-fold resistant to mitoxantrone was isolated by serial passage
      of the parental wild-type MCF-7 cells (MCF/WT) in stepwise increasing
      concentrations of drug. MCF/MX cells were also approximately 10-fold cross
      resistant to doxorubicin and etoposide but were not cross-resistant to
      vinblastine. Intracellular accumulation of radiolabeled mitoxantrone was markedly
      reduced in MCF/MX cells relative to that in the drug-sensitive MCF/WT cells. This
      decrease in intracellular drug accumulation into MCF/MX cells was associated with
      enhanced drug efflux, which was reversed when cells were incubated in the
      presence of sodium azide and 2, 4-dinitrophenol, suggesting an energy-dependent
      process. Incubation of MCF/MX cells with verapamil did not affect either the
      accumulation of mitoxantrone or the level of resistance in these cells.
      Furthermore, RNase protection and Western blot analyses failed to detect the
      expression of the mdr1 RNA or P-glycoprotein, a drug efflux pump known to be
      associated with the development of multidrug resistance in vitro. However, a
      polyclonal antibody directed against a synthetic peptide corresponding to the
      putative ATP binding domain of P-glycoprotein reacted with two (M(r) 42,000 and
      85,000) membrane proteins from MCF/MX cells which were not found in MCF/WT.
      Functional assays and Western blot analysis for topoisomerase II revealed no
      differences in topoisomerase II activity or protein levels in MCF/MX cells. Thus,
      resistance in this cell line is apparently associated with enhanced drug efflux
      involving a pathway distinct from the mdr1-encoded multidrug transporter P
      glycoprotein.

PMID- 1358432
TI  - Selective inhibition of tumor cell growth by a recombinant single-chain antibody
      toxin specific for the erbB-2 receptor.
AB  - A high percentage of human breast and ovarian tumors display amplified c-erbB-2
      gene copies, leading to overexpression of the growth factor receptor. Its
      membrane location and elevated expression make the erbB-2 protein an appropriate
      target for a directed tumor therapy. We have used recombinant DNA technology to
      produce a single-chain antibody-exotoxin A (scFv-ETA) fusion protein which
      specifically binds the human erbB-2 receptor. The scFv portion is composed of the
      heavy- and light-chain variable domains of a monoclonal antibody which recognizes
      the extracellular domain of the human erbB-2 receptor. The bacterially produced
      scFv-ETA protein was shown to bind specifically to cells expressing the human
      erbB-2 protein. The scFv-ETA inhibits protein synthesis in erbB-2-expressing
      tumor cells at doses ranging from 2 to 200 ng/ml and is cytotoxic for these cells
      at equivalent doses. In athymic nude mice, administration of the scFv-ETA
      inhibited the growth of erbB-2-overexpressing human ovarian carcinoma cells.

PMID- 1358433
TI  - Structural requirements of simple organic cations for recognition by multidrug
      resistant cells.
AB  - We previously noted that a wide variety of drugs which are recognized by
      multidrug-resistant cells (MDR+) are positively charged. However, it remains
      unclear why and how such a large number of structurally different compounds can
      be distinguished by MDR+ cells. The majority of the diverse compounds subject to
      MDR are complex and thereby complicate definitive structure/function
      characterization of the P-glycoprotein-mediated MDR mechanism. Using a series of
      simple aromatic (alkypyridiniums) and nonaromatic (alkylguanidiniums) organic
      cations differing in their lipophilicity by stepwise additions of single alkyl
      carbons, we demonstrate by growth inhibition studies that a single aromatic
      moiety and a critical degree of lipophilicity (log P > -1) are required for
      recognition of these simple organic cations by MDR+ cells. Thus, MDR+ cells are
      not cross-resistant to the nonaromatic guanidiniums but do show cross-resistance
      to those aromatic pyridiniums with chain lengths > four. Resistance ratios, as
      determined by comparison of 50% inhibitory doses in MDR- versus MDR+ cells,
      increase as a function of increasing chain lengths of these latter simple
      aromatic compounds. Resistance to pyridinium analogues in MDR+ cells is
      reversible by co-treatment with nontoxic doses of verapamil. Preliminary uptake
      data with radioactive analogues further implicate the MDR mechanism of lowered
      drug accumulation in accounting for resistance to the pyridinium homologues.
      Utilization of these simple organic cations provides a rational basis for better
      defining the physical chemical properties of more complex compounds processed by
      the MDR mechanism and suggests a strategy for designing chemotherapeutic agents
      with reduced susceptibility to MDR.

PMID- 1358434
TI  - Tumorigenic suppression of a human cutaneous squamous cell carcinoma cell line in
      the nude mouse skin graft assay.
AB  - The development of human squamous cell carcinomas has been associated with a
      number of genetic alterations involving chromosome 11, including cytogenetic and
      allelic deletions as well as amplification of genes in the 11q13 region. To
      determine the relevance of chromosome 11 in the formation of tumors of stratified
      squamous epithelial origin, we have introduced, via microcell fusion, a normal
      human chromosome 11 into the cutaneous squamous cell carcinoma cell line
      A3886TGc2. The ability of chromosome 11 to modulate the tumorigenicity of
      A3886TGc2 was evaluated first by inoculating cells s.c. in nude mice. All hybrids
      remained tumorigenic but exhibited longer tumor latencies than the parent, a
      result previously observed by other laboratories. We then tested our epidermally
      derived hybrids in the more physiologically relevant environment of the nude
      mouse skin graft system. The tumorigenic phenotype of three of four chromosome 11
      hybrids placed into nude mouse skin grafts was completely suppressed. Polymerase
      chain reaction amplification of DNA from normal skin present at the suppressed
      graft sites failed to detect the introduced human cells. This information
      indicates that the normal skin is of mouse origin and suggests that the
      chromosome 11 microcell hybrids did not differentiate in vivo, but most likely
      failed to survive. We propose that external environmental factors present at the
      site of inoculation modulate the tumorigenic potential of these cells.

PMID- 1358435
TI  - Expression and CpG methylation of the insulin-like growth factor II gene in human
      smooth muscle tumors.
AB  - Previously we have shown that expression of the insulin-like growth factor II
      (IGF-II) gene in 36 normal smooth muscle tissues (myometria) and 26 benign smooth
      muscle tumors (leiomyomas) was detectable by Northern blot analysis but that the
      RNA levels were low. In 9 of 20 malignant smooth muscle tumors (leiomyosarcomas)
      IGF-II gene expression was also low or absent, while in 11 of 20 the IGF-II gene
      was abundantly expressed. In 32 of these tissues we have now studied the DNA
      methylation state of the IGF-II gene. For the analysis of overall methylation of
      the gene the restriction endonucleases HpaII and MspI were used. In normal smooth
      muscle and in leiomyomas the IGF-II gene appeared to be methylated. In
      leiomyosarcomas with low IGF-II gene expression the DNA was partly demethylated.
      In leiomyosarcomas with abundant IGF-II gene expression overall methylation of
      the DNA tended to be low. In addition, we have studied the methylation state of
      one particular CpG site in the IGF-II gene with the restriction endonuclease
      AvaII. The results of the latter analysis confirm the analysis with HpaII and
      MspI. In conclusion, in malignant smooth muscle tumors the data indicate an
      inverse correlation between CpG methylation and expression of the IGF-II gene.

PMID- 1358436
TI  - Transcriptional repression of the neu protooncogene by estrogen stimulated
      estrogen receptor.
AB  - Both neu gene overexpression and loss of estrogen receptor (ER) expression have
      been found to correlate with a poor prognosis in human breast cancer. Studies of
      breast tumor specimens have suggested that these two factors are not independent,
      leading us to hypothesize that there is a causal relationship between loss of ER
      and overexpression of neu. In this report, we confirm that ER can negatively
      regulate the expression of the neu gene protein product, p185neu, in two ER
      positive but not an ER negative breast cancer cell line(s). We have produced
      sublines which stably express human ER from a previously ER negative human breast
      cancer cell line. We demonstrate that the expression of ER in these cell lines is
      sufficient to confer the ability to respond to estradiol by down-regulating neu
      expression at both the protein and RNA levels. Utilizing neu promoter
      chloramphenicol acetyltransferase constructs in transient cotransfection assays,
      we have also shown that this regulation occurs at the transcriptional level and
      requires the presence of both ER and estradiol. Furthermore, utilizing promoter
      deletion constructs, we provide evidence that a 140-base pair region of the neu
      promoter is required for this transcriptional regulation. When placed in a
      heterologous promoter, this 140-base pair region allows transcriptional
      repression by estradiol stimulated ER; thus, it represents an estrogen responsive
      region within the neu promoter. Finally, we have used gel mobility shift analysis
      to demonstrate an alteration in the nuclear factor(s) binding to this promoter
      region in estradiol stimulated versus estradiol deprived breast cancer cells.
      This study provides the first evidence that the inverse clinical correlation
      between neu and ER expression may be due to transcriptional repression of neu by
      estradiol stimulated ER.

PMID- 1358437
TI  - A new functional role for P-glycoprotein: efflux pump for benzo(alpha)pyrene in
      human breast cancer MCF-7 cells.
AB  - We propose that the cellular burden of certain carcinogens may be mitigated by P
      glycoprotein (P-gp), the putative drug efflux pump. In a series of multidrug
      resistant human breast cancer MCF-7 cells with increasing P-gp expression we
      examined this hypothesis using benzo(alpha)pyrene, a widely distributed
      environmental and dietary carcinogen. We found that multidrug resistant cells
      were cross-resistant to benzo(alpha)pyrene and the rates of efflux for
      benzo(alpha)pyrene were higher in multidrug resistant cells than in wild type
      cells. Evidence supporting the involvement of P-gp included the inhibition of
      azidopine binding to P-gp benzo(alpha)pyrene and the inhibition of
      benzo(alpha)pyrene efflux by Adriamycin and verapamil. Our findings suggest that
      P-gp may play a role in the cellular defense to carcinogens. The expression of P
      gp and the modulation of its function may affect the susceptibility of normal
      tissues to transformation by carcinogens.

PMID- 1358438
TI  - Evidence for the involvement of a potential second tumor suppressor gene on
      chromosome 17 distinct from p53 in malignant astrocytomas.
AB  - Molecular analysis of malignant astrocytomas demonstrated three distinct groups
      of tumors with chromosome 17p abnormalities, which include (a) deletion of the
      p53 locus (17p13.1) and mutations in the remaining allele, (b) deletion of the
      p53 locus but no detectable mutations in the remaining allele, and (c) deletions
      not including the p53 locus but mutations in one of the alleles. Furthermore,
      deletion mapping analysis demonstrated allelic loss of genes distal to
      D17S28/D17S5 markers (17p13.3) in group C tumors. The loss of heterozygosity of
      genes on chromosome 17 without detectable mutation (group B) or deletion (group
      C) in the p53 gene implies the presence of a second tumor suppressor gene in the
      telomeric region of 17p, the homozygous functional inactivation of which may play
      a role, either alone or in conjunction with p53, in the initiation and/or
      progression of astrocytic neoplasms.

PMID- 1358439
TI  - Cytotoxic T lymphocytes and immune surveillance.
AB  - Cytotoxic T lymphocytes recognize peptide fragments of cytoplasmic proteins
      presented by class I MHC molecules. Recently, these peptides have been shown to
      be short, usually nonamers, and their binding to particular class I molecules is
      now well understood. There is also detailed understanding of how proteins are
      processed to generate antigenic peptides and some knowledge of the T lymphocyte
      receptors involved. CTL have been shown to be important in controlling virus
      infections, including those that cause tumours. CTL have also been demonstrated
      against other tumours, and their activity may lead to the abnormalities of MHC
      class I molecule expression that are frequently observed on tumours. The overall
      role of CTL is probably to survey body cells for abnormalities, including those
      induced by virus infection and mutation, and to destroy potentially harmful
      cells.

PMID- 1358440
TI  - Thyroid hormone receptors and their role in development.
AB  - That most major physiological actions of thyroid hormones could be mediated via
      hormonal regulation of gene expression has been known for more than 25 years. The
      localization of TR in the cell nucleus, first reported almost 20 years ago,
      confirmed this concept. But it is only since the cloning of the TR gene and its
      identification as the c-erbA oncogene, accomplished 6 years ago, that we have
      begun to understand the details of the interaction between the hormone and its
      receptor and between the receptor and its target gene. Perhaps the most
      significant concept to emerge from the molecular studies is that the TR belongs
      to the superfamily of nuclear receptors for steroid hormones and morphogens such
      as retinoids. It highlights the evolutionary conservation of a major network of
      cellular signalling and intracellular regulatory pathways and which has helped
      bring us closer to a unified concept of the action of many growth and
      developmental hormones. Several important questions to be solved in the future
      become obvious from this brief review of the role of thyroid hormone in
      regulating developmental processes. Among these is the explantation for the high
      degree of tissue specificity of hormonal regulation of gene expression. The
      discovery of differential expression of the two major TR genes and the generation
      of multiple isoforms of the receptor by alternate splicing go some way to
      answering this question, but this is clearly not the sole factor determining
      tissue specificity. It will be most important to find out more about the
      interaction between the receptor and other transcription factors or nuclear
      proteins, some of which may be tissue specific and others expressed ubiquitously.
      The autoinduction of TR during amphibian metamorphosis, described above,
      emphasizes the intriguing question of how receptor genes are regulated during
      development. We know little as yet about the promoters and regulatory factors
      involved in this process. Finally, we have also described the recent recognition
      of genetic defects in TRs that underlie thyroid hormone linked diseases in
      humans. Future studies on the molecular genetics of receptors will enhance the
      importance in clinical practice of receptor linked diseases.

PMID- 1358441
TI  - The leukaemia oncogene v-erbA: a dominant negative version of ligand dependent
      transcription factors that regulates red cell differentiation?
AB  - The v-erbA oncogene of avian erythroblastosis virus alters the growth properties
      and arrests differentiation of chick erythroid progenitor cells. The v-erbA
      protein is a mutated, ligand independent version of the c-erbA/T3R alpha chick
      receptor for T3, a ligand dependent transcriptional regulator. In reconstituted
      systems using idealized hormone responsive elements, over-expressed v-erbA acts
      as a dominant repressor of transcription mediated by liganded c-erbA/T3R alpha.
      This property seems to account for at least part of the phenotype of AEV
      transformed erythroid cells and for the transcriptional repression of some
      erythrocyte specific genes. However, v-erbA is likely to interfere with
      regulatory circuits other than those directly regulated by T3 receptors. Aspects
      of this hypothesis are discussed in the context of available evidence for the
      role of T3 and other hormones in erythroid progenitor cells
      proliferation/differentiation.

PMID- 1358442
TI  - Pharmacologic controversy of CNS stimulants in Gilles de la Tourette's syndrome.
AB  - The controversy of the use of stimulants in Gilles de la Tourette's syndrome
      (GTS) can only be understood by examining the relationship between GTS and
      attention deficit-hyperactivity disorder (ADHD), because the relationship between
      the two disorders is complex, and stimulants are used in the one (ADHD) and may
      be contraindicated in the other (GTS). This relationship therefore has to be
      viewed from several perspectives, including clinical, genetic, neurobiochemical,
      neurophysiological, and treatment strategies, to highlight the complexities
      involved, and reasons for controversy. The present review will examine these
      relationships, and thus the evidence for and against the treatment of GTS with
      stimulants.

PMID- 1358443
TI  - [Heart insufficiency treated with beta-blocking agents. Comparison of responders
      and non-responders].
AB  - In the last few years several Authors reported positive results using beta
      blocking therapy in chronic heart failure. They also observed a group of patients
      who did not improve after this treatment. The aim of our study was comparing
      hemodynamic, neurohumoral and heart rate responses to beta-blockers in 2 groups
      of patients: Group A, patients who improved and Group B, patients who did not
      improve their clinical conditions after beta-blockade. We studied 26 patients
      with chronic heart failure of different origin: coronary artery disease and
      idiopathic dilative cardiomyopathy. They were treated with atenolol 50 mg/die for
      at least 1 year. Patients were divided into 2 groups: Group A including patients
      who increased the exercise time and the peak VO2 (> or = 2 ml/min/kg) and Group
      B, patients who did not increase exercise time and peak VO2 during beta-blockers.
      In Group A patients we observed a correlation between heart rate and end
      diastolic volume by scintigraphy. We did not observe this correlation in Group B
      patients. The ejection fraction, evaluated by scintigraphy, significantly
      increased in Group A, while in Group B did not change. In both groups of patients
      we observed that plasmatic norepinephrine decreased significantly. In our
      opinion, this reduction is not due to an amelioration of organ clearance, because
      it was observed even in patients who did not show an increase of cardiac index
      and of ejection fraction. We suggest that the decrease of plasmatic
      norepinephrine might be the effect of beta-blockade and that it is not related to
      clinical response after treatment.

PMID- 1358444
TI  - Improved isovolumetric relaxation in canine reperfused myocardium after beta 1
      adrenergic stimulation.
AB  - OBJECTIVE: beta 1 Adrenergic stimulation with the partial agonist xamoterol
      improves the systolic recovery of reperfused ("stunned") myocardium. The effects
      of this agent on isovolumetric relaxation and diastolic ventricular filling were
      evaluated. METHODS: In 15 open chest dogs, the distal left circumflex coronary
      artery was occluded for 15 min and then reperfused. Eight dogs served as placebo
      controls, and seven received xamoterol (100 micrograms.kg-1 intravenously) at 10
      min reperfusion. Diastole was divided into an isovolumetric relaxation phase and
      a subsequent filling phase, and wall excursion velocities were calculated.
      RESULTS: In the control group isovolumetric wall thinning velocity in the
      reperfused myocardium recovered only slowly, from -5.67(SD 5.29) mm.s-1 at 10 min
      reperfusion to -4.84(6.35) mm.s-1 at 30 min reperfusion and 2.99(7.97) mm.s-1 at
      8 h reperfusion. Xamoterol increased isovolumetric wall thinning velocity in the
      reperfused myocardium, from -7.78(6.25) mm.s-1 at 10 min reperfusion to
      3.43(6.09) mm.s-1 at 30 min reperfusion, and 12.04(5.66) mm.s-1 at 8 h
      reperfusion, whereas wall thinning velocity during the filling phase was
      unaffected. At 8 h reperfusion the difference between the groups was still
      significant. When compared with the effects on systolic wall thickening velocity,
      the impairment of isovolumetric wall thinning velocity during occlusion and the
      improvement due to xamoterol were both more marked. These functional differences
      were not reflected by the two indices of global diastolic function, peak negative
      dP/dt and relaxation constant tau. CONCLUSIONS: beta 1 Adrenergic stimulation
      with xamoterol improves isovolumetric relaxation in reperfused myocardium more
      markedly than systolic contraction, but it has no direct effect during diastolic
      filling.

PMID- 1358446
TI  - Long-term effects of syrup medications for recurrent otitis media on the dental
      health of 6- to 8-year-old children.
AB  - The dental response to repeated antimicrobial and antihistamine medications was
      studied by comparing the dental health of 64 adenoidectomized children 5 years
      after surgery to that of 212 untreated controls. Annual dental recordings
      starting from the age of 3 years were obtained from health care centers. As
      expected, the proportion of children who had several (> or = 11) syrup
      medications was significantly higher (p < 0.001) in the adenoidectomized than in
      the control group. Sucrose-containing syrup medications were prescribed twice as
      often for the children of the adenoidectomized as for the control group (p <
      0.001). However, the average amount of antimicrobial syrup medications prescribed
      was 19.2 +/- (SD) 13.0 per child for the adenoidectomized as compared to 8.5 +/-
      8.3 for the control children (p < 0.001). The dmf value of the adenoidectomized
      children at the age of 3 years (mean +/- SEM: 0.5 +/- 0.1) was significantly (p <
      0.005) lower than that of the controls (1.1 +/- 0.2). The difference was still
      significant (p < 0.01) at the age of 4 years, but disappeared thereafter. In
      conclusion, the antibacterial syrup medication seemed to be associated with a
      significant decline in dental caries at first. The simultaneous use of
      antihistamines was, however, thought to delay normal tooth maturation, so that
      after discontinuation of the antimicrobial medication, accelerated formation of
      new carious lesions took place.

PMID- 1358445
TI  - Transmural heterogeneity of postjunctional alpha 2 adrenergic coronary
      vasoconstriction in hypoperfused cat left ventricle.
AB  - OBJECTIVE: The aim was to analyse the influence of coronary postjunctional alpha
      1 and alpha 2 adrenergic vasoconstriction in hypoperfused myocardium with special
      emphasis on transmural distribution of blood flow. METHODS: The left coronary
      artery was hypoperfused by means of a clamped shunt line. Sequential selective
      postjunctional alpha 1 (doxazosin) and alpha 2 (SK&F 104078) adrenergic
      antagonism was established following beta adrenergic antagonism with propranolol.
      Regional myocardial blood flow was measured with radiolabelled microspheres
      during equal coronary perfusion pressures. Experimental subjects were nine
      pentobarbitone anaesthetised open chest cats. RESULTS: Left coronary
      hypoperfusion decreased endocardial blood flow, whereas epicardial flow was
      unaltered. In this situation alpha 1 adrenergic antagonism did not affect
      myocardial blood flow. Subsequent alpha 2 antagonism impaired endocardial blood
      flow, whereas epicardial blood flow was augmented. Mean coronary vascular
      resistance declined following combined alpha 1 and alpha 2 adrenergic antagonism.
      CONCLUSIONS: Coronary alpha adrenergic vasoconstriction is localised mainly
      epicardially in hypoperfused myocardium and counteracts endocardial hypoperfusion
      distal to a fixed coronary stenosis. Furthermore, this vasoconstriction is of the
      postjunctional alpha 2 adrenergic subtype.

PMID- 1358447
TI  - Glucocorticoids stimulate transcription of the rat phenylethanolamine N
      methyltransferase (PNMT) gene in vivo and in vitro.
AB  - 1. Phenylethanolamine N-methyltransferase (PNMT) is regulated by glucocorticoid
      hormones. This study investigates the ability of glucocorticoids to modulate
      transcription of the rat PNMT gene in vivo and in vitro. 2. In the adrenal glands
      of hypophysectomized (HPX'd) rats, the synthetic glucocorticoid dexamethasone
      (DEX) stimulates production of PNMT mRNA. Quantitative hybridization reveals that
      the levels of PNMT mRNA increase approximately threefold in total and poly(A)+RNA
      after 4 days of DEX treatment of HPX'd rats, a level which is maximal for this
      treatment. 3. ACTH, the hormonal stimulus of glucocorticoid biosynthesis in the
      adrenal cortex, enhances PNMT mRNA production to levels comparable to that
      achieved with DEX in this system. The steroid responsiveness of PNMT message
      production is specific for glucocorticoids. DEX also increases PNMT mRNA in the
      brain stem, although the magnitude and speed of response are lower than observed
      in the adrenal gland. 4. Additional confirmation of the inductive ability of
      glucocorticoids is demonstrated by the increase in PNMT immunoprecipitated
      following translation in vitro of adrenal RNAs from DEX-treated rats.
      Furthermore, the PNMT mRNA signal obtained by in situ hybridization
      histochemistry in adrenal sections and in primary cultures of dispersed rat
      adrenal medullae reveals that DEX effects on PNMT mRNA can be elicited both in
      vivo and in vitro. 5. Specifically, glucocorticoids exert their effects on
      expression of PNMT mRNA by elevating the rate of PNMT gene transcription: a 2.3
      fold increase in PNMT transcription persists for 18 hr following DEX treatment of
      HPX'd rats. In summary, this study establishes that glucocorticoids directly and
      rapidly stimulate transcription of the rat PNMT gene.

PMID- 1358449
TI  - Microtubule-associated protein 2 (MAP2)-immunoreactive neurons in the retina of
      Bufo marinus: colocalisation with tyrosine hydroxylase and serotonin in amacrine
      cells.
AB  - Neuron populations in the retina of the toad, Bufo marinus, were labelled with a
      monoclonal antibody raised against microtubule-associated protein 2 (MAP2). A
      subpopulation of cones, probably corresponding to the blue-sensitive small single
      cones, large diameter amacrine cells in the most proximal row of the inner
      nuclear layer and some large ganglion cells in the ganglion cell layer were
      labelled. Double labelling experiments were carried out to establish the
      colocalisation of MAP2 with known putative transmitter substances of the anuran
      amacrine cells. MAP2 was colocalised in a subpopulation of serotonin
      immunoreactive and in all tyrosine hydroxylase-immunoreactive amacrine cells. The
      results indicate, that the MAP2 content in the neurons of the anuran retina can
      be correlated with other well-defined neurochemical and/or physiological
      properties.

PMID- 1358448
TI  - A combined evaluation of biochemical and morphological changes during human
      neuroblastoma cell differentiation.
AB  - 1. The effects of retinoic acid, gamma-interferon, cytosine arabinoside, nerve
      growth factor, tumor necrosis factor, and 12-O-tetradecanoylphorbol 13-acetate on
      the human neuroblastoma cell line, LAN-5, were studied. Intracellular levels of
      acetylcholinesterase, neuron-specific enolase, catecholamines and related
      neurotransmitters, vasointestinal peptide, and substance P were evaluated after
      induction. 2. Cell morphology was strongly affected by retinoic acid, gamma
      interferon, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13-acetate. The
      main effects of retinoic acid and gamma-interferon were the loosening of cell
      clusters and the extension of long neurites; cytosine arabinoside induced cell
      body swelling and marked neuritogenesis. Following 12-O-tetradecanoylphorbol 13
      acetate treatment, the cells became small, round, and neuritic. Conversely,
      modifications induced by nerve growth factor and tumor necrosis factor were mild.
      Cell proliferation rate was reduced by retinoic acid, gamma-interferon, cytosine
      arabinoside, and 12-O-tetradecanoylphorbol 13-acetate, while nerve growth factor
      and tumor necrosis factor were devoid of effects. 3. Acetylcholinesterase
      activity was significantly stimulated by retinoic acid and by gamma-interferon.
      Neuron-specific enolase activity was unaffected by all treatments except 12-O
      tetradecanoylphorbol 13-acetate, which enhanced it by 1.6-fold. 4. The cellular
      catecholamine and related metabolite content was lowered by retinoic acid and
      gamma-interferon, while cytosine arabinoside and, even more, 12-O
      tetradecanoylphorbol 13-acetate showed a stimulatory activity on their
      intracellular accumulation. 5. Finally, the cell-associated vasointestinal
      peptide level was strikingly increased by gamma-interferon and, to a lesser
      extent, by retinoic acid, cytosine arabinoside, and 12-O-tetradecanoylphorbol 13
      acetate. 6. It is concluded that the most relevant biochemical changes associated
      with LAN-5 cells differentiation involve the repertoire of neurotransmitters and
      neuropeptides. These events vary in quality and in quantity, likely due to the
      pattern complexity of gene expression triggered by each inducer in determining
      the diversity of neuronal phenotypes.

PMID- 1358450
TI  - Immunocytochemical localization of muscarinic acetylcholine receptors in the rat
      endocrine pancreas.
AB  - Immunocytochemical application of the antimuscarinic acetylcholine receptor
      antibody M35 to pancreas tissue revealed the target areas for the parasympathetic
      nervous system. Immunoreactivity in the endocrine pancreas was much higher than
      that in the exocrine part. Moreover, the endocrine cells at the periphery of the
      islets of Langerhans displayed the highest level of immunoreactivity. Based on
      these findings in the mantle of the islets, two types of islets have been
      distinguished: type-I islets with intensely stained mantle cells, and type-II
      islets with a much lower concentration of these cells. On average, type-I islets
      were larger (244.8 microns +/- 6.1 SEM) than type-II islets (121.5 microns +/-
      3.8 SEM). M35-immunoreactivity was present on the majority of D cells, which were
      characterized by their immunoreactivity to somatostatin [of 446 D cells 356
      (79.8%) were M35-immunopositive]. However, only a small proportion of the
      intensely stained mantle cells belonged to the D cell population. Therefore, it
      is concluded that the majority of the intensely stained mantle cells represent
      glucagon-secreting A and/or pancreatic polypeptide-secreting F cells. The
      intensity of M35-immunoreactivity at the periphery and central core of the islets
      paralleled the density of cholinergic innervation, suggesting a positive
      correlation between the intensity of cholinergic transmission and the number of
      muscarinic acetylcholine receptors at the target structures. The present study
      further revealed some striking parallels for the muscarinic acetylcholine
      receptor characteristics between the (endocrine) pancreas and the central nervous
      system.

PMID- 1358451
TI  - Bethanechol and a G-protein activator, NaF/AlCl3, induce secretory response in
      Paneth cells of mouse intestine.
AB  - Paneth cells located at the bottom of intestinal crypts may play a role in
      controlling the bacterial milieu of the intestine. Using morphometry to clarify
      the secretory mechanism of the Paneth cells, we studied the ultrastructural
      changes in mouse Paneth cells produced following intra-arterial perfusion with
      Hanks' balanced salt solution containing a cholinergic muscarinic secretagogue
      (bethanechol), a neuroblocking agent (tetrodotoxin), or a G-protein activator
      (NAF/AlCl3). Bethanechol (2 x 10(-4) mol/l) induced Paneth-cell secretion. Many
      Paneth cells massively exocytosed their secretory material into the crypt lumen;
      the enhanced secretion caused degranulation and vacuole formation. However,
      tetrodotoxin (2 x 10(-6) mol/l) did not prevent the bethanechol-enhanced
      secretion by the Paneth cells. NaF (1 x 10(-2) mol/l) and AlCl3 (1 x 10(-5)
      mol/l) induced massive exocytosis of the Paneth cells; the exocytotic figures
      were similar to those observed in mice stimulated by bethanechol. G-protein
      activation was followed by a sequence of intracellular events, resulting in
      exocytosis.

PMID- 1358452
TI  - Characterization of a RFamide-positive subset of ganglionic cells in the
      hydrozoan planular nerve net.
AB  - The complexity of the hydrozoan planular nervous system was examined. Using a
      whole-mount technique with indirect immunofluorescence, the spatial pattern of
      ganglionic cells showing RFamide-like immunoreactivity was visualized. RFamide
      antiserum bound a subset of ganglionic cells in the anterior and upper middle
      regions of the planula and a few ganglionic cells in the upper tail region.
      Labeled cells consisted of bipolar and multipolar neurons. Stained processes from
      these cells formed a three-dimensional nerve net that followed the contour of the
      mesoglea; such fibers were striking in terms of their large numbers, long
      lengths, and organization into distinct bundles. Labeled fibers were seen to
      contact other ganglionic cells, sensory cells, epithelio-muscle cells, the
      mesoglea, and the outside free surface. All stained cell bodies and fibers were
      found in the ectoderm. Using the same technique the reappearance of RFamide
      positive ganglionic cells in epithelial tissue of chimeric grafts of planulae was
      observed. Interstitial cells capable of forming RFamide-positive ganglionic cells
      underwent extensive anterior-posterior migrations in the grafts, moved into the
      epithelial tissue, and differentiated into RFamide-positive ganglionic cells.
      Stained repopulated ganglionic cells always formed in the same position in the
      epithelial tissue as was observed in control planulae suggesting that the
      expression of RFamide-like substances may be position dependent in the planula.

PMID- 1358453
TI  - Immunocytochemical and circadian biochemical analysis of neuroactive amino acids
      in the pineal gland of the rat: effect of superior cervical ganglionectomy.
AB  - Semiquantitative immunocytochemistry by immuno-gold techniques revealed
      differences in the spatial distribution of glutamate, glutamine, and taurine
      within the pineal gland, with greatest labeling over pinealocytes, glia, and
      endothelia, respectively. At the subcellular level, glutamate labeling tended to
      be highest over pinealocyte synaptic ribbons and mitochondria, and lowest over
      lipid inclusions. Pineal levels of glutamate, glutamine and taurine, as measured
      by high performance liquid chromatography, did not vary over a light: dark cycle.
      Superior cervical sympathetic denervation, which abolishes pineal melatonin
      synthesis, resulted in a nearly 50% reduction in pineal glutamate levels, but had
      no effect on levels of glutamine and taurine. Other amino acids (alanine,
      arginine, aspartate, serine) were reduced by 23%-33% following sympathectomy.
      These data suggest an important role for glutamate in pinealocyte function(s)
      possibly related to the noradrenergic innervation of the gland.

PMID- 1358455
TI  - Ovarian innervation develops before initiation of folliculogenesis in the rat.
AB  - Sympathetic neurotransmitters have been shown to be present in the ovary of the
      rat during early postnatal development and to affect steroidogenesis before the
      ovary becomes responsive to gonadotropins, and before the first primordial
      follicles are formed. This study was undertaken to determine if development of
      the ovarian innervation is an event that antedates the initiation of
      folliculogenesis in the rat, Rattus norvegicus. Serial sections of postnatal
      ovaries revealed a negligible frequency of follicles 24 h after birth (about 1
      primordial follicle per ovary). Twelve hours later there were about 500 follicles
      per ovary, a number that more than doubled to about 1300 during the subsequent 12
      h, indicating that an explosive period of follicular differentiation occurs
      between the end of postnatal days 1 and 2. Electron microscopy demonstrated that
      before birth the ovaries are already innervated by fibers containing clear and
      dense-core vesicles. Immunohistochemistry performed on either fetal (day 19) or
      newborn (less than 15h after birth) ovaries showed the presence of
      catecholaminergic nerves, identified by their content of immunoreactive tyrosine
      hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. While
      some of these fibers innervate blood vessels, others are associated with
      primordial ovarian cells, thereby suggesting their participation in non-vascular
      functions. Since prefollicular ovaries are insensitive to gonadotropins, the
      results suggest that the developing ovary becomes subjected to direct neurogenic
      influences before it acquires responsiveness to gonadotropins.

PMID- 1358456
TI  - Vasoreactivity of the intracranial internal carotid artery.
AB  - The vasoreactivity of the intracranial segment of the internal carotid artery to
      transmitters, present in the perivascular sympathetic, parasympathetic and
      sensory nerves, as well as to other vasoactive agents of relevance for headache,
      was tested in man and monkey. The total arterial segment from both species is
      equipped with contractile receptors for noradrenaline, serotonin, prostaglandin
      F2 alpha, ergotamine and sumatriptan. Further, the total arterial segment dilated
      upon exposure to calcitonin gene-related peptide in both species. Other
      vascoactive transmitters, acetylcholine, substance P and neurokinin A, caused
      only weak dilatation, restricted to the proximal extracavernous segment in the
      monkey. The findings are discussed in relation to the pathogenesis and treatment
      of cluster headache.

PMID- 1358454
TI  - Evidence for projections from medullary nuclei onto serotonergic and dopaminergic
      neurons in the midbrain dorsal raphe nucleus of the rat.
AB  - The anterograde tracer Phaseolus vulgaris-leucoagglutinin was injected into the
      medial nucleus of the solitary tract and into the rostral dorsomedial medulla. A
      sequential two-color immunoperoxidase staining was accomplished in order to
      demonstrate the co-distribution of presumed terminal axons with chemically
      distinct neurons in the dorsal raphe nucleus of the midbrain central gray, i.e.,
      B7 serotonergic and A10dc dopaminergic neurons. Black-stained efferent fibers
      from the medial nucleus of the solitary tract and the rostral dorsomedial medulla
      intermingled with brown-stained serotonergic (5-hydroxytryptamine-immunoreactive)
      or dopaminergic (tyrosine hydroxylase-immunoreactive) neurons. Light microscopy
      revealed that the black-stained efferent axons exhibited numerous en passant and
      terminal varicosities that were often found in close apposition to brown-stained
      serotonergic and dopaminergic somata, and to proximal and distal dendrites and
      dendritic processes. The close association of immunoreactive elements suggests
      the presence of axo-somatic and axo-dendritic synaptic contacts of medullary
      fibers with serotonergic and dopaminergic neurons in the dorsal raphe nucleus.
      These projections could be involved in the modulation of dorsal raphe neurons,
      depending on the autonomic status of an animal.

PMID- 1358457
TI  - Homeotic genes of the Bithorax complex repress limb development in the abdomen of
      the Drosophila embryo through the target gene Distal-less.
AB  - Homeotic genes encode transcription factors that are thought to specify segmental
      identity by regulating expression of subordinate genes. Limb development is
      repressed in the abdominal segments of the Drosophila embryo by the hometic genes
      of the Bithorax complex (BX-C). Localized expression of the homeobox gene Distal
      less (DII) is required for leg development in thoracic segments. We have
      identified a minimal cis-regulatory enhancer element that directs DII expression
      in the larval leg primordia. We present evidence that the BX-C proteins repress
      DII expression in abdominal segments by binding to a small number of specific
      sites in this element. Mutating these sites eliminates BX-C protein binding and
      renders the element insensitive to BX-C-mediated repression in vivo. Repression
      of limb development in the abdomen appears to be controlled at the DII enhancer.
      Thus DII may serve as a downstream target gene through which the homeotic genes
      control abdominal segment identity in the Drosophila embryo.

PMID- 1358458
TI  - D type cyclins associate with multiple protein kinases and the DNA replication
      and repair factor PCNA.
AB  - Human cyclin D1 has been associated with a wide variety of proliferative diseases
      but its biochemical role is unknown. In diploid fibroblasts we find that cyclin
      D1 is complexed with many other cellular proteins. Among them are protein kinase
      catalytic subunits CDK2, CDK4 (previously called PSK-J3), and CDK5 (also called
      PSSALRE). In addition, polypeptides of 21 kd and 36 kd are identified in
      association with cyclin D1. We show that the 36 kd protein is the proliferating
      cell nuclear antigen, PCNA. Cyclin D3 also associates with multiple protein
      kinases, p21 and PCNA. It is proposed that there exists a quaternary complex of D
      cyclin, CDK, PCNA, and p21 and that many combinatorial variations (cyclin D1, D3,
      CDK2, 4, and 5) may assemble in vivo. These findings link a human putative G1
      cyclin that is associated with oncogenesis with a well-characterized DNA
      replication and repair factor.

PMID- 1358459
TI  - Vertebrate homeobox gene nomenclature.

PMID- 1358460
TI  - Role of the production of natural killer cell stimulatory factor (NKSF/IL-12) in
      the ability of B cell lines to stimulate T and NK cell proliferation.
AB  - We have previously used human Epstein Barr virus (EBV)-transformed B
      lymphoblastoid cell lines for the identification and purification of a novel
      cytokine, natural killer cell stimulatory factor (NKSF/IL-12), that has
      pleiotropic effects on human lymphocytes. B cell lines are also routinely
      employed as feeder cells for the culture of T and natural killer (NK) cells. In
      this report we describe the ability of two NKSF/IL-12 producing B cell lines
      (RPMI-8866 and Cess) and two nonproducing lines (Raji and Daudi) to stimulate the
      proliferation of T and NK cells in 8-day PBL cultures. We demonstrate, using an
      anti-NKSF/IL-12 neutralizing monoclonal antibody, that the endogenous production
      of NKSF/IL-12 in these cultures can significantly enhance the proliferation and
      cytotoxic activity of T and NK cells. We also report that the addition of
      exogenous rNKSF/IL-12 can greatly increase the number of T and NK cells obtained
      from the cultures following stimulation by the B cell lines. Aside from the
      possible practical applications, the enhanced proliferation of T and NK cells
      consistently observed in the presence of endogenously produced NKSF/IL-12 or
      exogenously added rNKSF/IL-12 in this system may further our understanding of the
      role of this cytokine during an in vivo immune response.

PMID- 1358461
TI  - Selective activation of murine V beta 8.2 bearing T cells by Pseudomonas exotoxin
      A.
AB  - We have determined that Pseudomonas aeruginosa exotoxin A (PE) can selectively
      stimulate the proliferation of V beta bearing T lymphocytes. Murine thymocytes
      were fractionated by selective agglutination with peanut agglutinin (PNA) and the
      PNA- thymocytes, which represent mature thymocytes, were shown to be responsive
      to PE stimulation. In addition, mature peripheral T lymphocytes (nylon wool
      nonadherent splenocytes) were also observed to respond to PE stimulation. Both
      CD4+ and CD8+ splenic T lymphocyte populations proliferated in response to PE.
      Flow microfluorimetry analysis of PNA- thymocytes stimulated with PE indicated
      that V beta 8.2 bearing T cells were preferentially expanded. Thus, our data
      indicate that PE represents a microbial super antigen which stimulates murine
      thymocytes which bear the V beta 8.2 element of the T cell receptor.

PMID- 1358462
TI  - Acetylated alpha-tubulin in the pollen tube microtubules.
AB  - Three monoclonal alpha-tubulin antibodies YL 1/2 (Kilmartin et al., 1982), 6-11B
      1 (Piperno and Fuller, 1985) and DM1A (Blose et al., 1984) were used in indirect
      immunofluorescence (IIF) microscopy of the microtubule (MT) cytoskeleton in
      tobacco (Nicotiana tabacum) pollen tubes. The majority of pollen tube MTs contain
      tyrosinated alpha-tubulin recognized by YL 1/2. Acetylated alpha-tubulin revealed
      by 6-11B-1 was detected in the generative cell and in the kinetochore fibers, in
      polar spindle regions, and in the cell plate of the phragmoplast during
      generative cell division. In addition, small fragments of acetylated microtubules
      were seen in the older parts of the pollen tube grown on a taxol medium. The
      interaction of pollen tube MTs with mAb 6-11B-1 suggested that acetylation of
      alpha-tubulin correlates well with the putative arrays of stable MTs.

PMID- 1358463
TI  - Infectious pancreatic necrosis virus internalization and endocytic organelles in
      CHSE-214 cells.
AB  - The early events that take place during the internalization of infectious
      pancreatic necrosis virus (IPNV) into Chinook salmon embryo cells (CHSE-214) were
      analyzed ultrastructurally. Endocytic tracers were employed in order to
      characterize the organization of endocytic organelles in CHSE-214 cells, as well
      its relation to the IPNV penetration. Results demonstrate that IPNV appear
      internalized within vesicular compartments which are located peripherally in CHSE
      214 cells. Despite the high rate of infectious multiplicity few virus particles
      were detected inside the cells. Endocytic tracer labelling of tubulovesicular
      elements and endosomes of host cells showed a well developed endocytic apparatus.
      Results suggest that endocytosis may be involved during the initiating events in
      the productive IPNV infection.

PMID- 1358464
TI  - Somatostatin receptors.
AB  - The neuropeptide somatostatin (SRIF) is a neurotransmitter in the brain that
      exerts physiological actions including the modulation of Ca2+ and K+
      conductances, neuronal cell firing, neurotransmitter release, and certain
      behaviors such as locomotion and cognitive functions. SRIF induces its biological
      effects by interacting with cell surface receptors. Recent studies have revealed
      that subtypes of SRIF receptors exist in the brain and other tissues. The SRIF1
      receptor can be distinguished by its high affinity for the agonist MK 678, is
      coupled to G proteins, and mediates the stimulatory effects of SRIF on a delayed
      rectifier K+ current in brain neurons. Furthermore, MK 678, when applied to the
      nucleus accumbens, evokes locomotor activity, and SRIF1 receptors in this brain
      region selectively mediate the stimulation of this behavioral response to SRIF.
      SRIF1 receptors are unevenly distributed in the brain, with high levels in the
      dentate gyrus of the hippocampus, the locus coeruleus, the neostriatum, and the
      inner layers of the cerebral cortex. This receptor subtype has characteristics
      similar to the recently cloned SRIF receptor, SSTR2. A second SRIF receptor
      subtype has been identified in the brain and is referred to as the SRIF2
      receptor. It has no affinity for MK 678, can be selectively labeled with smaller
      structural analogs of the peptide CGP 23996, and has characteristics similar to
      the recently cloned receptor subtype SSTR1. SRIF2 receptors are not efficiently
      coupled to G proteins and have a distinct but overlapping distribution in brain
      with SRIF1 receptors. No clear biological function has been identified for SRIF2
      receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358465
TI  - Tendon injuries of the foot and ankle.
AB  - Tendon injuries are often caused by direct trauma or overuse. Pathology may
      consist of inflammatory lesions external to the tendon sheath or inflammation of
      either the peritenon, sheath, or tendon. This article reviews the diagnosis and
      treatment of injuries to the peroneal, peroneus brevis, peroneus longus, anterior
      tibial, flexor hallucis longus, and posterior tibial tendons.

PMID- 1358466
TI  - Cloning and genetic analyses of two highly polymorphic, moderately repetitive
      nuclear DNAs from Phytophthora infestans.
AB  - Randomly selected clones from a Phytophthora infestans partial genomic library
      were characterized by hybridizing individual clones to Southern blots of total
      genomic DNA digested with the restriction enzyme EcoRI. Among 59 clones that were
      screened on seven different central-Mexican isolates, five revealed a unique
      banding pattern for each isolate tested. Two of these clones were tested further;
      the banding patterns produced by both were somatically stable when probed to DNA
      from 63 single-zoospore (asexual) progeny from five different "parent" isolates.
      For one probe, RG57, each band appeared to represent a unique genetic locus in
      three different crosses, and each locus segregated for the presence or absence of
      a band. No bands were found to be allelic, but two pairs of cosegregating loci
      were identified. Genetic analyses of the other probe (RG7) revealed many more
      pairs of cosegregating bands and some bands which were allelic. When these probes
      were hybridized to DNA from the other five species in Phytophthora group IV,
      probe RG57 hybridized strongly to DNA from P. colocasiae, P. phaseoli and P.
      mirabilis, but weakly or not at all to that of P. hibernalis and P. ilicis. Probe
      RG7 hybridized fairly strongly to DNA from all six species. Because the sequence
      recognized by probe RG57 appears to be evolutionarily conserved, and is
      dispersed, moderately repetitive and highly polymorphic, it could be very useful
      in additional studies on the genetics and population biology of P. infestans.

PMID- 1358467
TI  - Mitochondrial DNA of Schizophyllum commune: restriction map, genetic map, and
      mode of inheritance.
AB  - Mitochondrial DNA (mtDNA) found in the basidiomycete Schizophyllum commune
      (strain 4-40) is a circular molecule 49.75 kbp in length. A physical map
      containing 61 restriction sites revealed no repeat structures. Cloned genes from
      Neurospora crassa, Aspergillus nidulans, and Saccharomyces cerevisiae were used
      in Southern hybridizations to locate nine mitochondrial genes, including a
      possible pseudogene of ATPase 9, on the restriction map. A probe from a
      functional ATPase 9 gene identified homologous fragments only in the nuclear
      genome of S. commune. Restriction fragment length polymorphisms (RFLPs) between
      mtDNA isolated from different strains of S. commune were used to show that
      mitochondria do not migrate with nuclei during dikaryosis.

PMID- 1358468
TI  - Transmission of mitochondrial DNA in Ustilago violacea.
AB  - Mitochondrial DNA (mtDNA) restriction fragment length polymorphisms (RFLPs) were
      used as genetic markers for following mitochondrial transmission in the
      basidiomycete Ustilago violacea. Yeast-like cells of opposite mating types (a1
      and a2) were mated on 2% water agar and were treated with alpha-tocopherol to
      induce formation of dikaryotic hyphae. Upon depletion of the alpha-tocopherol,
      the hyphae budded off haploid cells with parental nuclear genotypes. These cells
      were examined for mitochondrial RFLP phenotype. In progeny expressing the a1
      mating type, mitochondria from either parent were observed equally frequently. In
      progeny with the a2 mating type, mitochondria were almost exclusively (94%) from
      the a2 parent.

PMID- 1358469
TI  - Maternal transmission of mitochondrial DNA in interspecific hybrids of Populus.
AB  - Restriction fragment analysis was conducted to investigate the mode of
      inheritance of mitochondrial (mt) DNA in F1 progeny of two P. deltoides x P.
      deltoides, three P. deltoides x P. nigra, and two P. deltoides x P. maximowiczii
      controlled crosses, and in Populus x canadensis by using 16 restriction
      endonucleases and two heterologous probes of cloned mtDNA fragments of maize.
      Five restriction fragment length polymorphisms (RFLPs) of mtDNA differentiated P.
      deltoides from P. nigra, whereas three RFLPs of mtDNA separated P. deltoides from
      P. maximowiczii. In all cases, F1 progeny of P. deltoides x P. nigra, and P.
      deltoides x P. maximowiczii, crosses had mtDNA restriction fragments of only
      their maternal P. deltoides parents. P. x canadensis had mtDNA restriction
      fragments of only P. deltoides. F1 progeny of intraspecific P. deltoides crosses
      also had the same mtDNA fragments as their maternal parent. The results clearly
      demonstrate uniparental-maternal inheritance of the mitochondrial genome in F1
      interspecific hybrids of P. deltoides with P. nigra and P. maximowiczii.

PMID- 1358470
TI  - Studies on antiulcer drugs. V. Synthesis and antiulcer activity of
      aralkylbenzazoles.
AB  - A series of 2-alkylamino-5- or 6-aralkyl-substituted benzazoles were synthesized
      and tested for histamine H2-receptor antagonist and anti-stress ulcer activities.
      These new compounds showed little or no histamine H2-receptor antagonist activity
      in contrast to imidazo[1,2-a]pyridine analogues (I). On antiulcer assay, however,
      some pyridine derivatives (II) exerted higher activity than the reference
      compounds, sofalcone, sucralfate and cimetidine. The structure-activity
      relationships of these compounds are discussed.

PMID- 1358471
TI  - Lipid lowering effects of high linoleate and high alpha-linolenate diets in rats
      and mice. Consequence of long-term feedings.
AB  - Diets high in linoleate (safflower oil) or high in alpha-linolenate (perilla oil)
      were fed to rats for 11 months, and the effects of the diets on plasma and tissue
      lipids were compared. The plasma levels of total cholesterol (Cho), phospholipids
      (PL) and triacylglycerol (TG) were significantly lower in the high alpha
      linolenate group than in the high linoleate group, the differences being more
      than 30% in the levels of total Cho and TG. The diets had differential effects on
      the lipid contents of major tissues: the TG level in muscle was higher but both
      the TG level in depot fat and the PL level in muscle were lower in the high alpha
      linolenate group than in the high linoleate group. In order to clarify whether or
      not the hypolipidemic effect of the high alpha-linolenate diet was due to changes
      in the distribution of lipids among tissues, whole body lipids were estimated in
      mice fed these diets for 5 months. The whole body Cho content was significantly
      lower, by 28%, in the high alpha-linolenate group compared with the high
      linoleate group, but the total lipid content, PL and neutral lipids were similar
      between the groups. Our results indicate that the high alpha-linolenate diet has
      a more potent cholesterol lowering effect in plasma and body tissue than the high
      linoleate diet; interestingly, whole body TG levels are similar but tissue
      distributions of TG are different between the two dietary groups.

PMID- 1358472
TI  - Corroding characteristics of Eikenella corrodens.
AB  - Fourteen strains of Eikenella corrodens isolated from human oral cavity were
      studied to determine corroding characteristics. Nine out of the 14 strains
      produced corroding colonies under anaerobic culture condition. One of them
      produced corrosion even in an aerobic culture. No morphological differences in
      surface structures were observed between corroding and non-corroding strains of
      E. corrodens by transmission electron microscopy. The morphology of corroding
      colonies of E. corrodens was then examined by scanning electron microscopy. The
      surface of the corroding-colony center was smoothly convex. A boundary line was
      clear between the smooth center and the surrounding corrosion region. Double or
      triple frill-like structures surrounded the center portion with small
      convexities. Spreading bacterial masses were observed in the outer portion of the
      colony. Morphological observations of the corroding colony edge indicated that a
      surface translocation termed "twitching motility" or "gliding motility" occurs in
      the outer portion and plays a role in its colonization of periodontal regions.

PMID- 1358473
TI  - QT intervals at heart rates from 50 to 120 beats per minute during 24-hour
      electrocardiographic recordings in 100 healthy men. Effects of atenolol.
AB  - BACKGROUND: Conflicting reports about changes in QT intervals suggest that QT
      values should be compared at similar heart rates. METHODS AND RESULTS: Relations
      between QT and RR intervals were determined after measurement of QT values by
      Holter recording at heart rates of 50, 60, 70, 80, 90, 100, 110, and 120 beats
      per minute in 100 healthy young men. Fifteen men underwent a second recording
      during acute treatment with the beta-blocking agent atenolol. At heart rates
      between 80 and 120 beats per minute, the QT interval was significantly longer
      (from 9 to 16 msec), and at a heart rate of 50 beats per minute significantly
      shorter (26 msec), than values calculated from Bazett's formula. Sleep prolonged
      QT values by 18 msec at a heart rate of 60 beats per minute and by 21 msec at a
      heart rate of 50 beats per minute compared with the waking state. Atenolol
      lengthened QT intervals significantly (by 11-14 msec) at heart rates between 90
      and 110 beats per minute and shortened them (by 12 msec) at a heart rate of 60
      beats per minute. During sleep, QT intervals were the same before and after
      atenolol. CONCLUSIONS: The method of plotting QT against RR intervals after
      measurement of QT values at similar stable spontaneous heart rates before and
      after intervention allows changes in autonomic state and heart rate to be taken
      into account. By this method, QT values can be compared without distortion
      effects caused by correction formulas.

PMID- 1358474
TI  - Cardiovascular Surgery 1991. Council on Cardiovascular Surgery, American Heart
      Association Scientific Sessions. Anaheim, California, November 11-14, 1991.

PMID- 1358475
TI  - Reduction of infarct size with coronary venous retroperfusion.
AB  - BACKGROUND: The purpose of this study was to determine whether coronary venous
      retroperfusion with pressure-controlled intermittent coronary sinus occlusion
      (PICSO) alone and in combination with coronary venous substrate enhancement using
      L-glutamate would decrease ischemic damage after surgical revascularization for
      an acute coronary occlusion. METHODS AND RESULTS: In 40 pigs, the second and
      third diagonal vessels were occluded with snares for 90 minutes followed by 30
      minutes of cardioplegic arrest and 180 minutes of reperfusion with the coronary
      snares released. During the period of coronary occlusion, 10 pigs received PICSO
      using a balloon-tipped triple-lumen catheter in the coronary sinus; 10 pigs
      received PICSO plus oxygenated blood transfused retrograde via the PICSO catheter
      (7 ml/min), 10 pigs received PICSO plus an oxygenated blood L-glutamate (13 mM)
      solution, and 10 pigs received neither PICSO, blood, nor L-glutamate through the
      coronary sinus (unmodified). Hearts treated with PICSO had higher wall motion
      scores (1.27 +/- 0.33 for unmodified, 2.40 +/- 0.40* for PICSO, 2.45 +/- 0.20*
      for PICSO plus blood, 2.85 +/- 0.30* for PICSO plus L-glutamate; *p < 0.05 from
      unmodified where 4 is normal to -1 is dyskinesia), lower area of necrosis-to-area
      of risk ratio using histochemical staining techniques (73 +/- 4% for unmodified,
      27 +/- 4 for PICSO; 18 +/- 2* for PICSO plus blood, 12 +/- 1* PICSO plus L
      glutamate; *p < 0.05 from unmodified), significantly less tissue acidosis (pH)
      compared with the unmodified group (pH, -0.41 +/- 0.13 for unmodified, -0.16 +/-
      0.03* for PICSO, -0.19 +/- 0.02* for PICSO plus blood, -0.20 +/- 0.08* for PICSO
      plus L-glutamate; *p < 0.05 from unmodified). CONCLUSIONS: Coronary venous
      retroperfusion with PICSO alone and in combination with coronary venous substrate
      enhancement using L-glutamate significantly decreases ischemic damage during
      urgent surgical revascularization.

PMID- 1358476
TI  - Effect of antibody to leukocyte adhesion molecule CD18 on recovery of neonatal
      lamb hearts after 2 hours of cold ischemia.
AB  - BACKGROUND: Prior studies have shown that leukocytes are important in reperfusion
      injury after normothermic ischemia, and recently discovered leukocyte adhesion
      molecules that bind to endothelial ligands may be involved in this process. No
      studies on the role of leukocyte adhesion molecules in hypothermic ischemia are
      available. METHODS AND RESULTS: We assessed the effect of preischemic
      administration of monoclonal antibody to the leukocyte adhesion molecule CD18 on
      recovery of isolated blood-perfused neonatal lamb hearts arrested for 2 hours
      with 15 degrees C K+ cardioplegic solution by comparing nine antibody-treated and
      nine control hearts. At 30 minutes after reperfusion, antibody-treated hearts
      compared with control hearts had better percent recovery of maximum left
      ventricular (LV) developed pressure (83.9 +/- 2.2% versus 73.6 +/- 3.0%, mean +/-
      SEM), LV dP/dt (78.4 +/- 3.3% versus 67.4 +/- 3.4%), coronary blood flow (159.5
      +/- 12.2% versus 84.4 +/- 3.5%), and myocardial oxygen consumption (129.8 +/-
      16.5% versus 71.2 +/- 6.2%) (all p < 0.05). In each heart, we also tested
      coronary vascular resistance (CVR) response to 10(-6) mol/l acetylcholine (ACh)
      infusion to assess endothelial function. Percent recovery of CVR response to ACh
      was higher in antibody-treated hearts (38.4 +/- 4.3%) than control hearts (13.4
      +/- 12.8%) (p = 0.08). CONCLUSIONS: These results suggest that leukocyte
      adherence to endothelium mediated by CD18 plays an important role in reperfusion
      after hypothermic ischemia. Antibody to CD18 may be useful in myocardial and
      endothelial protection during surgically induced ischemia.

PMID- 1358477
TI  - Progression-Regression of Atherogenesis: Molecular, Cellular, and Clinical Bases.
      Symposium proceedings. Scottsdale, Arizona, April 5-7, 1991.

PMID- 1358478
TI  - Expression of the gene encoding tyrosine hydroxylase in a subpopulation of quail
      dorsal root ganglion cells cultured in the presence of insulin or chick embryo
      extract.
AB  - Avian sensory ganglia contain a population of normally latent autonomic
      precursors with catecholaminergic potentialities. The present study examines the
      expression of the tyrosine hydroxylase (TH) gene in quail dorsal root ganglia
      (DRG) by both in situ hybridization and polymerase chain reaction (PCR)
      techniques. In situ hybridization using quail TH cDNA as a probe demonstrated the
      presence in DRG cell cultures of TH mRNA in a subpopulation of cells that never
      express the adrenergic phenotype in vivo. Expression of the TH gene in autonomic
      precursor cells of DRG in culture is totally dependent on the presence either of
      insulin or chick embryo extract. The numbers of catecholaminergic cells
      expressing TH mRNA and TH immunoreactivity evolve in a closely similar manner
      during the culture period. Using two primers, specific for highly conserved 5'
      regions of TH cDNA, it was possible to detect the same band of DNA amplified by
      PCR in total RNA from DRG cultures grown in the presence of insulin, sympathetic
      ganglia and adrenal gland. No amplified DNA was detected in uncultured DRG cells.
      These data further indicate that, under the influence either of insulin or a
      still unknown factor contained in the CEE, the TH gene is induced in a
      subpopulation of DRG cells.

PMID- 1358479
TI  - Effect of insulin and insulin-like growth factor I on the expression of the
      catecholaminergic phenotype by neural crest cells.
AB  - Neural crest-derived catecholaminergic precursors have been used as a model to
      study the role of signals supplied by the environment during avian neurogenesis.
      A new culture system consisting of dissociated sclerotomes or somites isolated at
      embryonic day 3 (E3) or 2.5 (E2.5) has been established, which allows
      quantitative comparison of various culture conditions. As a first step of this
      study, the role of insulin and insulin-like growth factor I (IGF-I) in
      catecholaminergic differentiation has been investigated. Our results show that
      both factors are able to increase by a factor 2 to 3 the number of
      catecholaminergic cells present in the culture of sclerotomes after 24 h of
      culture. The effect is dose-dependent and the half-maximal effect is obtained
      with low concentrations of each peptide. Since insulin, IGF-I and their
      respective receptors are present at this stage of development in avian embryo,
      our observations suggest that an early step in catecholaminergic differentiation
      could be under at least the partial control of insulin and insulin-related
      peptides. On the other hand, neural crest precursors isolated at E2.5 are not
      able to generate catecholaminergic cells and to respond to insulin when
      cultivated for one day, indicating that these precursors are subjected in vivo to
      a maturation step, within the somite/sclerotome between E2.5 and E3; this step
      could be obtained in vitro by cultivating the precursors for 1 day, which
      resulted in the development of insulin responsiveness by catecholaminergic
      precursors.

PMID- 1358480
TI  - Early appearance of tyrosine hydroxylase immunoreactivity in the retina of human
      embryos.
AB  - In the retina of 6 post-ovulatory week old human embryos, tyrosine hydroxylase
      (TH) immunoreactivity is expressed in retinoblasts in the peripheral retina, and
      ganglion-like cells with an axon in the optic nerve in the posterior retina. This
      is the first report on the expression of a catecholamine marker in a sub
      population of migrating retinoblasts. Since in the adult retina the only TH+
      cells are a sub-population of amacrine cells, the expression of this enzyme in
      some ganglion-like cells must represent either a transient developmental event,
      or indicate that these cells subsequently undergo transformation through axonal
      degeneration.

PMID- 1358481
TI  - Analysis for transaminases in serum with an amperometric glutamate electrode.
AB  - We determined transaminases in human blood serum with an amperometric glutamate
      biosensor. The probe was a hydrogen peroxide sensor assembled with appropriate
      selective membranes to enhance the probe specificity and lifetime. Calibration
      curves of glutamate were linear in the range 1-1000 mumol/L, with a response time
      of < 1 min. This probe was subsequently applied to the measurement of activities
      of aspartate and alanine aminotransferases in human sera. Analytical recovery
      studies demonstrated the suitability of the glutamate sensor by measuring 91-99%
      of added glutamate, 92-106% of added aspartate aminotransferase, and 101-105% of
      added alanine aminotransferase. Transaminase activity measured in 80 sera
      correlated well with results obtained with a spectrophotometric procedure.

PMID- 1358482
TI  - Characterization of dipeptidyl peptidase IV (CD26) from human lymphocytes.
AB  - The membrane-bound dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5) has been
      purified 5,400-fold from human peripheral blood mononuclear cells. The
      purification procedure included detergent solubilization and successive
      chromatography on DEAE Sepharose Fast Flow, Con A Sepharose, Cu2+ loaded metal
      chelating Sepharose, Sephacryl S-300 High Resolution and Q Sepharose Hiload. The
      molecular mass of the native, detergent solubilized enzyme estimated by gel
      filtration was 264.kDa. Chromatofocusing indicated a pI of approximately 5.0. The
      pI optimum was 8.7. The enzymatic activity of the purified preparation was
      irreversibly inhibited by N-(H-Phe-Pro)-O-(4-nitrobenzoyl)hydroxylamine
      hydrochloride in the micromolar range. The binding of purified DPP IV to CD26
      monoclonal antibodies confirmed the identity between CD26 and dipeptidyl
      peptidase IV. The purification and characterization of lymphocytic dipeptidyl
      peptidase IV is of great value for the identification of its natural substrates
      and for the study of its physiological significance in the T-lymphocyte function.

PMID- 1358483
TI  - Evaluation of serum basal thyrotrophin levels and thyrotrophin receptor antibody
      activities as prognostic markers for discontinuation of antithyroid drug
      treatment in patients with Graves' disease.
AB  - OBJECTIVE: We evaluated whether antithyroid drug treatment could be terminated
      more appropriately when both the serum basal thyrotrophin (TSH) level and TSH
      receptor antibody activity have become normal. DESIGN: This was a prospective
      randomized study of patients with Graves' disease followed for a mean of 28
      months after the withdrawal of antithyroid drug treatment. PATIENTS AND
      INTERVENTIONS: A total of 174 patients with hyperthyroid Graves' disease were
      entered consecutively into this study, 11 of whom were subsequently excluded. One
      hundred and sixty-three patients were divided randomly into two groups having
      different criteria for the discontinuation of the antithyroid drug. Group 1
      consisted of 79 patients whose antithyroid drug treatment was discontinued if
      both their serum TSH level and thyrotrophin binding inhibitor immunoglobulin
      (TBII) activity normalized. Group 2 consisted of 84 patients who were treated for
      24 months irrespective of their serum TSH level and TBII activity. All patients
      were treated initially with 400 mg/day of propylthiouracil followed by decreasing
      doses that maintained a euthyroid state. MEASUREMENTS: Serum basal TSH levels and
      TBII activities were measured using a radioimmunometric assay and a radioreceptor
      assay, respectively, every 2 months during the antithyroid drug treatment.
      RESULTS: The remission rate of Group 1 (51.9%) was not significantly different
      from that (63.1%) of Group 2. The mean duration of treatment in Group 1 was 10.2
      +/- 4.5 months (range 5-24, median 10). Median duration of treatment in Group 1
      was 14 months shorter than in Group 2. In Group 1, the relapse rate was
      independent of the duration of the treatment. Further, the mean duration of
      treatment in the relapsed patients was not significantly different from that for
      patients who went into remission (9.9 +/- 3.8 vs 10.7 +/- 5.7 months; P greater
      than 0.1). In Group 2, the relapse rate was dependent on the time when both the
      serum TSH level and TBII activity were normalized (chi 2 = 27.0, d.f. = 4; P less
      than 0.001). When both the serum TSH level and TBII activity were normalized, the
      relapse rate of Group 2 was not significantly different from that of Group I for
      treatment periods of 6-12 months (25 vs 24.2%, P greater than 0.1), 12-18 months
      (33.3 vs 40%, P greater than 0.1), and 18-24 months (46.2 vs 50%, P greater than
      0.1). However, the relapse rate of Group 2 was significantly lower than that of
      Group 1 when there was only a 6-month treatment period (5.6 vs 42.9%, P less than
      0.05). Of the clinical and laboratory parameters measured, male sex, change of
      goitre size during treatment, and TSH levels and TBII values at the end of
      treatment, were of prognostic significance in predicting a relapse. CONCLUSION:
      The present study suggests that antithyroid drugs treatment can be terminated
      more appropriately when both the serum TSH level and TBII activity are made
      normal, thus avoiding prolonged and unnecessary drug treatment.

PMID- 1358484
TI  - The pulsatile GH secretion in acromegaly: hypothalamic or pituitary origin?
AB  - OBJECTIVE: We studied the effects of different modes of octreotide therapy on the
      pulsatile pattern of GH release in an attempt to define better its regulation by
      growth hormone-releasing hormone (GHRH) and somatostatin and its effects on IGF-I
      plasma levels in acromegaly. DESIGN: In six acromegalic patients not cured by
      previous treatment we compared the 24-hour GH secretion profiles under basal
      conditions with subcutaneous (s.c.) bolus injections of 100 micrograms octreotide
      every 8 hours and with continuous s.c. infusions of the same daily dose. Blood
      samples were taken every 10 minutes over 24 hours followed by a GHRH test (100
      micrograms GHRH i.v.) with blood sampling every 15 minutes for another 2 hours.
      After a 4-week interval all patients were treated either by the bolus or
      continuous mode of octreotide application in a randomized cross-over design. On
      day 4 of treatment blood sampling and GHRH test were repeated. Octreotide
      treatment was withdrawn for another 4 weeks; all patients then received the
      alternate application mode and were measured under similar conditions.
      MEASUREMENTS: Serum GH and plasma IGF-I concentrations were analysed by serial
      array averaging. IGF-I levels were measured in two different assays with and
      without previous protein extraction. For GH pulse detection three different
      algorithms (Cluster, Pulsar, Desade) were applied. RESULTS: With both treatments,
      the initially elevated basal 24-hour mean serum GH concentrations (58.0 +/- 9.7
      mU/l mean +/- SEM) decreased significantly (bolus: 11.5 +/- 4.9 mU/l, P < 0.001
      vs basal; continuous infusion: 7.6 +/- 1.9 mU/l, P < 0.001 vs basal) after 4
      days. GH suppression was significantly more pronounced following continuous
      infusion than bolus (P < 0.05). IGF-I plasma concentrations were lowered
      significantly (P < 0.05) with both forms of treatment which did not differ
      between themselves. Bolus and continuous infusion treatment significantly
      inhibited (P < 0.05) the amplitudes of pulsatile GH release, but did not change
      the pulse frequency. In two of the patients, GHRH stimulation did not increase GH
      serum levels suggesting a constitutive activation of adenylyl cyclase.
      CONCLUSION: Continuous subcutaneous octreotide treatment in acromegaly suppresses
      mean GH levels better than bolus injection. The number of GH pulses remains
      unaffected by both modes of treatment providing evidence against a
      somatostatinergic mechanism of pulsatile GH secretion in these patients. The
      unchanged frequency of pulsatile GH release in the patients unresponsive to
      exogenous GHRH indicates that this pattern might be independent of hypothalamic
      GHRH and somatostatin and suggests a pituitary-derived mechanism for GH pulse
      generation in acromegaly.

PMID- 1358485
TI  - Patterns of renal function in hypertension due to unilateral renal artery
      occlusion.
AB  - We performed renal function studies in dogs with chronic renovascular
      hypertension produced by complete occlusion of a renal artery. In addition, we
      evaluated in anesthetized dogs the acute effects of a novel angiotensin
      converting enzyme inhibitor, CGS 16,617, on renal function and plasma
      neurohormones (epinephrine, norepinephrine and vasopressin) 4 weeks after
      initiation of 2 kidney, 1 clip hypertension. CGS 16,617 effectively decreased
      blood pressure in renal hypertensive animals. This response was associated with
      suppression of angiotensin II indicating effective converting enzyme inhibition.
      In the non-clipped kidney, acute administration of CGS 16,617 increased effective
      renal plasma flow but not glomerular filtration rate and urinary sodium
      excretion. In the clipped kidney, CGS 16,617 caused no change in any parameter of
      renal function. Plasma norepinephrine, epinephrine and vasopressin were
      unaffected by administration of CGS 16,617. These studies showed that chronic
      occlusion of a renal artery does not result in renal infarction because of a
      compensatory increase in the amount of blood provided through capsular collateral
      vessels. The collateral circulation which has developed in the clipped kidney
      explains the lack of a converting enzyme inhibitor effect.

PMID- 1358486
TI  - X-linked lymphoproliferative disease: prenatal detection of an unaffected
      histocompatible male.
AB  - Chorionic Villous Biopsy (CVS) for diagnosis of XLP was undertaken at 10 weeks
      gestation in an obligate carrier. The fetus was found to be male by cytogenetic
      analysis. XLP (Xq25-q26) is closely linked to the RFLP markers DXS10, DXS37 and
      DXS42, but only DXS10 (distal to XLP) was informative for prenatal diagnosis in
      this family. RFLP analysis using this marker gave a 7% risk that the fetus was
      affected, based on the known recombination frequency between DXS10 and XLP.
      Further investigation was then undertaken to obtain a rapid and more accurate
      diagnosis using the three highly polymorphic PCR based markers. These were the AC
      repeat markers DXS424 (XL5A) and DXS425 (XL90A3) and the tetramer repeat marker
      within HPRT. DX425 is approximately 10 cM proximal to DXS10 and HPRT but is not
      known with certainty to map proximal or distal to XLP. DXS424 is proximal to
      DXS10 and HPRT and was inferred to be proximal to XLP on the basis of map
      distance from HPRT estimated by linkage analysis of data from CEPH pedigrees.
      This was confirmed by a recombinant in the XLP family between DXS424 and DXS425,
      placing DXS424 proximal to XLP. Diagnosis by linkage using DXS424 and DXS425, at
      least one of which is proximal to XLP, and distal markers DXS10 and HPRT,
      increased the accuracy of diagnosis using flanking marker analysis to greater
      than 99% that the fetus was unaffected. HLA DR typing of the CVS showed that the
      fetus was DR identical to a male sibling with XLP. HLA compatibility was
      confirmed at delivery by full HLA typing and MLC.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1358487
TI  - DNA polymorphisms of the apolipoprotein B gene in Chinese coronary artery disease
      patients.
AB  - Five restriction fragment length polymorphisms (RFLP) of the apo B gene and their
      association with serum lipids and apolipoprotein levels have been studied in 139
      Chinese patients with angiographically confirmed CAD (mean age 56.2 +/- 0.8
      years) and 154 healthy Chinese subjects (mean 44.0 +/- 1.0 years) of both sexes.
      The patient group had significantly higher levels of serum total and LDL
      cholesterol; and apo B (P < 0.001) and lower HDL cholesterol and apo A-I (P <
      0.001 and < 0.01, respectively). The frequencies of the rarer alleles of the
      ins/del, XbaI and EcoRI (but not the PvuII and MspI) polymorphisms were
      significantly lower in the Chinese compared to those reported in Caucasians.
      There was no significant difference in allelic frequencies of the signal peptide
      region (Ins/Del), XbaI, MspI and EcoRI sites of the apo B gene between the
      patient and control groups. The frequency of the rarer allele of the PvuII RFLP
      was significantly lower in the CAD patients (P < 0.05) compared to that in the
      control group (0.05 vs 0.10). None of the DNA polymorphisms was associated with a
      significant influence on serum lipid and apolipoprotein levels in the patients
      with coronary artery disease.

PMID- 1358489
TI  - Nucleotide sequence and PCR-amplification of a polymorphic MboI site in human DNA
      marker D4S95 linked to the Huntington disease locus.
AB  - The nucleotide sequence of the probe BS674E-D defining the genetic locus D4S95
      was assessed, and used for designing PCR-primers amplifying a 175 bp fragment
      containing a polymorphic MboI site. With the described conditions it is now
      possible to use PCR followed by digestion for rapid determination of genotype in
      this marker system.

PMID- 1358488
TI  - Clinical variability of cardio-facio-cutaneous syndrome: report of two additional
      cases.
AB  - We describe two new cases of cardio-facio-cutaneous (CFC) syndrome, and underline
      the clinical variability of the CFC phenotype in our two patients presenting with
      border-line psychomotor development. The first patient showed some additional
      clinical manifestations, such as cryptorchidism and scoliosis, and the second one
      had atypical skin lesions.

PMID- 1358490
TI  - Human polymorphonuclear leucocytes stimulated by tumour necrosis factor-alpha
      show increased adherence to extracellular matrix proteins which is mediated via
      the CD11b/18 complex.
AB  - The present study demonstrates that tumour necrosis factor (TNF) and FMLP, but
      not IL-1 or IL-8, enhanced the adherence of polymorphonuclear neutrophil (PMN) to
      fibronectin, an extracellular matrix protein. The adherence induced by FMLP was
      very rapid, within 5 min while the induction of adherence by TNF was much slower,
      reaching maximum at 60 min. TNF also enhanced an adhesion of PMN to other
      extracellular matrix proteins, such as laminin, collagen IV and gelatin II, but
      not to human serum albumin. Anti-CD18 MoAb completely inhibited the binding of
      TNF-stimulated PMN to fibronectin and partially inhibited the binding to laminin.
      Further investigation showed that adhesion of TNF-stimulated PMN to fibronectin
      and laminin was inhibited by anti-CD11b MoAb and to a lesser extent by CD11a
      MoAb. In contrast to TNF-stimulated PMN the binding of unstimulated PMN to
      fibronectin and laminin was only inhibited by anti-CD11a MoAb. Anti-CD11c had no
      effect on PMN adherence. These results suggest that unstimulated PMN adhere to
      extracellular proteins through the CD11a/18, while TNF-stimulated PMN adhere
      through the CD11b/18. These results suggest that TNF secreted at the site of
      inflammation may enhance the interaction of PMN with the extravascular
      environment through the CD11b/18 complex.

PMID- 1358491
TI  - Leukotriene B4-induced hyperadhesiveness of endothelial cells for neutrophils:
      relation to CD54.
AB  - Leukotriene B4 (LTB4) induced an in vitro transient state of hyperadhesiveness in
      cultured human umbilical vein endothelial cells (HUVEC), leading to a 2.2-fold
      increase in the binding of neutrophil granulocytes (PMN), which was less than
      that conferred by platelet activating factor (PAF) though more than thrombin did
      (3.4- or 2.0-fold increases, respectively). This study concerns the role of the
      adhesive molecules CD18 and CD54 for the LTB4- (as well as thrombin- and PAF-)
      induced endothelial hyperadhesiveness. The MoAbs 60.3 (to the CD18 molecule on
      PMN) and 84H10 (to one epitope of CD54 on the HUVEC) blocked the adherence of PMN
      to LTB4-treated HUVEC, whereas MoAb LB-2 (directed at another CD54 epitope)
      failed to do so. MoAb 84H10 blocked 43% of the thrombin-induced
      hyperadhesiveness, whereas the PAF response was unaffected. Thus, LTB4-induced
      HUVEC hyperadhesiveness may therefore be related to a specific domain on the CD54
      (or on an antigenically related molecule) as well as being dependent on CD18,
      whereas the involvement of CD54 was much less or non-existent for the thrombin
      and PAF responses, respectively.

PMID- 1358493
TI  - Severe hemorrhagic complications from infection with nephropathia epidemica
      strain of Hantavirus.
AB  - In the following we describe a case of severe hemorrhagic fever with renal
      syndrome (HFRS) caused by Puumala infection. The diagnosis was made by
      immunofluorescence technique and by solid phase enzyme immunoassay using
      recombinant nucleocapsid antigen of a Puumala serotype strain. Such a clinical
      course with severe bleeding complications is considered untypical for Puumala
      induced HFRS.

PMID- 1358492
TI  - Cellular responses to human chondrocytes: absence of allogeneic responses in the
      presence of HLA-DR and ICAM-1.
AB  - To assess the accessory cell function of human articular chondrocytes, we
      assessed the ability of human chondrocytes to stimulate allogeneic peripheral
      blood mononuclear cells (PBMC) and to support phytohaemagglutinin (PHA)-induced
      proliferation of highly purified T cells. We also examined the surface expression
      of HLA-DR and ICAM-1 on the chondrocytes both unstimulated and stimulated with
      cytokines in vitro. Chondrocytes failed to stimulate allogeneic PBMC despite the
      constitutive expression of MHC class I molecules and the cytokine-induced
      expression of class II molecules but were able to support T cell proliferation to
      PHA, IFN-gamma and to a limited extent, IL-1 beta, induced class II expression on
      chondrocytes. ICAM-1 was present on 94-99% of freshly isolated cells; this
      declined with culture (17-59%; P < 0.005) but was readily induced by IFN-gamma,
      IL-1 beta, and tumour necrosis factor-alpha. Alloreactivity and, presumably,
      autoreactivity to chondrocytes requires factors in addition to the surface
      expression of DR and ICAM-1. However the presence of these molecules suggests a
      capacity for cell-cell interactions in inflammatory sites such as the cartilage
      pannus junction.

PMID- 1358494
TI  - Dose-response variation among different populations.

PMID- 1358495
TI  - The effects of rilmenidine on tests of autonomic function in humans.
AB  - The effects of rilmenidine, a new centrally acting antihypertensive agent, on a
      number of tests of autonomic function were investigated in six healthy male
      volunteers. Baroreflex function (delta RR interval [in milliseconds] with each
      millimeter of mercury change in systolic blood pressure) was determined in
      response to changes in pressure after injections of phenylephrine and
      nitroglycerin. Reflex cardiovascular responses to handgrip and standing, as well
      as during deep breathing and the Valsalva maneuver, were also investigated.
      Rilmenidine produced a dose-dependent decrease in blood pressure that was not
      accompanied by an increase in heart rate. Under conditions of low basal
      sympathetic activity, rilmenidine enhanced parasympathetic tone during the early
      reflex heart rate changes that occur immediately after standing and during deep
      breathing, as well as baroreflex heart rate responses to phenylephrine. During a
      test of sympathetic function, standing blood pressure, and heart rate after 3
      minutes, rilmenidine reduced sympathetic tone.

PMID- 1358496
TI  - Pharmacodynamics and pharmacokinetics of intramuscular dexmedetomidine.
AB  - The pharmacodynamics and pharmacokinetics of intramuscular dexmedetomidine--a
      novel alpha 2-adrenergic receptor agonist under development for preanesthetic use
      -were studied in healthy male volunteers. Single intramuscular doses of
      dexmedetomidine (0.5, 1.0, and 1.5 microgram/kg) and placebo were administered to
      six subjects in a single-blind, multiple crossover study. Dexmedetomidine induced
      dose-related impairment of vigilance assessed both objectively and subjectively.
      The drug also caused moderate decreases in blood pressure and heart rate. Plasma
      norepinephrine was dose-dependently (maximum 89%) decreased. The intramuscular
      doses resulted in linearly dose-related plasma concentrations of dexmedetomidine.
      Pharmacokinetic calculations revealed a time to maximum concentration from 1.6 to
      1.7 hours, an elimination half-life of 1.6 to 2.4 hours, an apparent total plasma
      clearance of 0.7 to 0.9 L/hr/kg, and apparent volume of distribution of 2.1 to
      2.6 L/kg. The sedative effect of dexmedetomidine dissipated during the 6-hour
      observation time, but all other effects were still evident 6 hours after
      administration of the higher doses, paralleling the plasma concentration curves.
      The relationship of plasma concentrations of dexmedetomidine to pharmacodynamic
      variables was consistent with a linear pharmacodynamic model. The pharmacodynamic
      pharmacokinetic profile of intramuscular dexmedetomidine may be suited to the
      proposed preanesthetic clinical use of this alpha 2-agonist.

PMID- 1358497
TI  - Autoantibodies in systemic lupus erythematosus.

PMID- 1358499
TI  - Gastrointestinal disorders requiring surgical treatment in patients with AIDS.

PMID- 1358500
TI  - Recent progress in the treatment of Parkinson's disease.
AB  - Because of the number of different types of anti-Parkinsonian medications, a
      number of options in the treatment of PD are now available. Each patient's
      medication regimen should be individualized. Many of the medication choices are
      made based on the stage of the disease. For patients who have newly diagnosed PD,
      and who are on no medications, treatment with deprenyl should be strongly
      considered. While some controversy remains concerning its possible slowing of the
      rate of disease progression, there is no evidence to suggest that its use is
      detrimental. It is generally well tolerated in patients with early disease. These
      factors must be weighed against the cost of the medication, and the fact that
      little if any therapeutic effect is seen in most patients who are not being
      treated with LD. A useful analogy when considering this issue is the prophylactic
      use of aspirin for cerebrovascular or cardiovascular disease. Newly diagnosed
      patients requiring treatment, who have tremor as their only symptom or their most
      prominent symptom, may be given an anticholinergic medication. Patients who have
      significant bradykinesia, rigidity or gait disturbance can be given amantadine. A
      combination of these two medications may be useful, and a combination of deprenyl
      with an anticholinergic drug or amantadine may provide excellent relief of early
      symptoms. At some point, most patients' symptoms progress such that treatment
      with LD is considered. Given its possible, but unproven, acceleration of the rate
      of disease progression, this decision should be weighed carefully. In a
      relatively young patient who may be treated for many years, a dopamine receptor
      agonist can be initiated without LD therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358498
TI  - [Contribution of glutathione to detoxification in alcoholism. Biochemical
      clinical studies].
AB  - The effects of reduced glutathione (GSH) administration (1.2 g/day and 2.4 g/day
      intravenously) on erythrocyte glutathione levels, serum gamma-glutamyl
      transpeptidase activity (GGTP) and urinary glucaric acid elimination were studied
      in a population of 24 chronic alcoholics voluntarily admitted to a 30 day
      detoxification protocol in comparison to a 12 patient control group treated only
      with chlordiazepoxide (initial dose 75-100 mg/day). Glutathione treatment
      increases dose-dependently and in a significant way erythrocyte glutathione
      levels and hastens the recovery of serum GGTP and urinary glucaric acid
      elimination. The relationship between glutathione, GGTP and glucaric acid is
      discussed, suggesting the possible role of GSH against the oxidative damage of
      alcohol.

PMID- 1358501
TI  - Identification of infant and adult swine susceptible to enterotoxigenic
      Escherichia coli by detection of receptors for F4(K88)ac fimbriae in brush
      borders or feces.
AB  - We attempted to determine F4(K88)-adhesive and non-adhesive phenotypes of infant
      (neonatal < 3 day old and weaned < 4 week old pigs) and adult (> 6 month old)
      swine by ELISA using immobilized F4(K88)ac fimbrial antigen or whole F4(K88) + E.
      coli cells (strains M1823 and 1476) and isolated small intestinal brush borders
      or easily-obtainable fecal samples from the same animals. Nineteen of 22 neonates
      (86%), 17 of 20 weaners (85%), and 26 of 39 adults (67%) were classified
      identically as F4(K88) receptor-positive or negative by the ELISA. The ELISA with
      feces from adult swine was found to be almost equally specific (87%) as that with
      feces from neonatal (90%) and weaned (91%) pigs. However, the sensitivity of the
      assay was low (38%), indicating that fecal samples from adults contained less
      receptor-material than necessary for comparable phenotyping. The receptor
      positive brush borders from neonates and weaners reacted significantly better (P
      < 0.02, < 0.001 respectively) with purified F4(K88) antigen than did those from
      adults. There was good agreement between the average ELISA values for feces from
      infant and adult swine regardless the source of coating antigen applied. With
      this assay we can determine F4(K88) phenotypes of infant swine using easily
      collected fecal samples rather than isolated brush borders. It was also concluded
      that tested feces is not an acceptable alternate source of the receptor-material
      to brush borders from F4(K88)-susceptible adult swine.

PMID- 1358502
TI  - Occurrence of fimbriae and enterotoxins in Escherichia coli strains isolated from
      piglets in Poland.
AB  - 1125 and 1146 E. coli strains isolated from suckling and weaned piglets with
      diarrhea, respectively, and 724 strains from healthy piglets were tested for the
      presence of fimbriae and production of enterotoxins. The fimbriae were determined
      by hemagglutination and slide agglutination tests, enterotoxins--by the use of
      ileal loop test in piglets (LT and STb enterotoxins) and suckling mouse assay
      (STa enterotoxin). It was found that 72.8 and 53.0% strains, isolated from
      diseased suckling and weaned piglets, respectively, possessed specific fimbrial
      hemagglutinins, in most cases with K88 antigen. Additionally, 987P fimbriae were
      detected in 14.0 and 0.7% strains isolated from piglets with diarrhea. Only 5
      strains (0.7%) recovered from healthy piglets had specific fimbriae, usually with
      undetermined antigenic structure. F1 fimbriae (called common or unspecific) were
      found in strains isolated both from diseased (15.2 and 16.3% strains,
      respectively) and healthy piglets (27.1% strains). It was noted that the strains
      isolated from suckling and weaned piglets with diarrhea in most cases were
      enterotoxigenic (90.5 and 69.1% strains, respectively) and most frequently
      produced heat-labile toxin LT alone or with STb. 18.5% of enterotoxigenic strains
      isolated from healthy piglets produced STa toxin.

PMID- 1358503
TI  - Characterization of chicken intestinal brush border membrane Na/H exchange.
AB  - 1. Na/H exchange is the major pathway for Na uptake in brush border membrane
      vesicles from chicken small intestine. Hanes-Woolf analysis demonstrated that Na
      and H competed at the same extravesicular site. The KNa for Na+ at extravesicular
      pH 6.6 is 35 mM and at pH 7.4, 12 mM. 2. Similar to mammalian intestinal cells,
      the Na/H exchanger does not appear to have an internal proton modifier site.
      Varying intravesicular pH from 6.1 to 7.8 stimulates uptake, but a sigmoidal
      relationship is not observed. 3. The ability of several amiloride analogs to
      inhibit the exchanger was tested and the inhibitory profile was similar, but not
      identical to Na/H exchangers in mammalian tissues. The potency series (from most
      to least potent) is hexamethylamiloride approximately ethylisopropylamiloride >
      methylisobutylamiloride > dimethylamiloride >> amiloride.

PMID- 1358504
TI  - Phosphatase activity in the hepatopancreas of Helix aspersa.
AB  - 1. Phosphatase acid (PhA) activity in the digestive gland (hepatopancreas) of the
      common garden snail Helix aspersa has been investigated using cytochemical
      methods. 2. All the cells composing this gland show PhA activity, the
      distribution pattern differing according to the cell type. 3. The digestive cells
      show the most widely distributed reaction product (brush border, phagolysosomes,
      multivesicular bodies and autophagic vacuoles). 4. In the excretory cells this
      activity appears in large sacs, while in the calcium cells the reaction product
      is abundant in the calcium granules. 5. Cellular digestion processes performed by
      each of these cell types is discussed together with their role in the
      detoxification of heavy elements derived from the environment.

PMID- 1358505
TI  - Anuran amphibia which are not acclimable to high salt, tolerate high plasma urea.
AB  - 1. The capacity of five anuran Amphibians (Bufo viridis, B. regularis, Rana
      ridibunda, Hyla arborea and Pelobates syriacus) to acclimate to NaCl and urea
      solutions was investigated. 2. All species could be acclimated to relatively high
      concentrations of urea solutions, while only Bufo viridis and Hyla arborea could
      be acclimated to 500 mOsm/kg or higher NaCl solutions. 3. The plasma urea
      concentration in B. viridis and H. arborea was elevated to levels over 140
      mmol/l. 4. The sum of plasma sodium and chloride concentrations did not increase
      over 400 mmol/l in any species. 5. Urine osmolality, which was normally low,
      increased, but never exceeded the plasma osmolality. 6. In the urea acclimation
      conditions, urine electrolytes diminished, similarly in all species in this
      study. 7. It is concluded that anuran Amphibians can tolerate high plasma urea
      concentrations, but only those species which can elevate it, either through
      retention or net synthesis, can be acclimated to high salt solutions.

PMID- 1358507
TI  - Carbonic anhydrase activity in blood of early sheep fetuses.
AB  - 1. The level of carbonic anhydrase activity in the red cells was measured in
      sheep fetuses at different times after conception: 39, 56, 77, 90 and 140 days,
      the last being close to full term. Measurements were also made on blood from four
      of the mothers. 2. There was a low level of the enzyme present in the 39 day
      fetuses (0.037 enzyme units (E.U.)/100 micrograms Hb) and its increase up to 90
      days of gestation (0.19 E.U./100 micrograms Hb) had a form approximating
      exponential. 3. The earliest levels were only 11% of the full term levels and
      only 4% of the adult levels previously reported. 4. Even the earliest samples
      were of blood that was fetal rather than embryonic but these results are the
      earliest carbonic anhydrase activities reported in this mammal.

PMID- 1358506
TI  - Effects of a low-sodium diet on electrolyte transport in the proximal and distal
      colon of the guinea pig (Cavia porcellus).
AB  - 1. Animals were randomly assigned to three different treatment groups. (I)
      Control group maintained on a standard guinea pig diet, (II) a group obtaining a
      low-Na diet (0.02% Na w/w) and (III) a group fed the low-Na diet and in addition
      being treated with K-canrenoate prior to the perfusion experiment. 2. Proximal
      and distal colonic segments of anesthetized guinea pigs were perfused
      simultaneously with Ringer's solution. 3. In the proximal colon of the control
      group Na and Cl were absorbed in equal quantity and K was secreted. 4. In the
      distal colon of the control group Na and K were absorbed and Cl was secreted. Na
      absorption was only approximately 1/10 of that in the proximal colon. 5. Feeding
      a low-Na diet for two weeks induced secondary hyperaldosteronism. Plasma
      aldosterone concentration increased 3.4-fold. Na and Cl absorption rose 34% and
      27% above control in the proximal colon, respectively. In the distal colon Na
      absorption was elevated 3.7-fold above control. 6. Na absorption and
      transepithelial potential difference (PD) in the proximal colon were amiloride
      insensitive in all groups. In the distal colon Na absorption was abolished by
      luminal amiloride and the transepithelial PD was reversed in polarity. 7. K
      canrenoate treatment prevented the increase in Na transport in the distal colon.

PMID- 1358508
TI  - The transfer of thyroxine from the mother to the young of the marsupials, the
      bandicoot (Isoodon macrourus) and the possum (Trichosurus vulpecula).
AB  - 1. The young of the bandicoot and possum are of similar weight at birth (200-250
      mg) but by day 50 post-partum have weights of 100 and 20 g, respectively. The aim
      of this study was to determine whether the disparate growth rate was associated
      with a difference in the transfer of thyroxine from mother to young. 2.
      Radioactive thyroxine was injected intramuscularly into the lactating female and
      24 hr later a blood sample was obtained from the mother and the pouch young
      removed. The amount of radioactive thyroxine remaining in the blood and within
      the young was determined. 3. The data obtained indicated that milk is a source of
      thyroid hormones in early pouch life. 4. The hypothesis that greater quantities
      of thyroxine are transferred in the milk of bandicoots than that of brushtail
      possums is not supported.

PMID- 1358509
TI  - Diet restriction: a tool to prolong the lifespan of experimental animals. Model
      and current hypothesis of action.

PMID- 1358510
TI  - Alterations of cytoplasmic enzyme activities of liver in rats fed on diets
      containing orotic acid with dietary fibers.
AB  - 1. Rats were fed with diets containing orotic acid with dietary fibers to induce
      alteration of lipid metabolism and cytoplasmic enzyme activities in the livers.
      Concentrations of blood glucose, serum insulin and free fatty acids (FFA) were
      measured. 2. In CP (cellulose + orotic acid) group compared to basal (cellulose -
      orotic acid) or CBH (corn bran hemicellulose + cellulose + orotic acid) groups,
      glucose-6-phosphate dehydrogenase, pyruvate kinase and ATP citrate lyase
      activities and FFA concentration were decreased according to lipid accumulation
      of livers. 3. In the CBH group, glycerokinase activity was higher than basal
      group.

PMID- 1358511
TI  - Changes in body composition of germ-free and conventional chickens during
      starvation.
AB  - 1. Changes in body composition during starvation were compared between germ-free
      (GF) and conventionalized (CVL) chicks in experiment 1. At 8 days of age, the GF
      birds were divided into two groups, i.e. GF and CVL groups. The CVL birds were
      inoculated with faeces from conventionally reared birds. Until 14 days of age,
      both birds were fed a diet ad lib. and thereafter starved for 6 days. 2. Nitrogen
      loss during starvation was significantly lower in CVL birds, though the reverse
      was true for water loss. Fasting heat production was comparable between two
      environments. 3. Influence of the gut microflora on body weight and nitrogen
      losses during starvation was investigated in birds prefed diets high or low in
      dietary protein in experiment 2. 4. No significant effect of the gut microflora
      was observed in body weight and nitrogen losses. Body weight was severely reduced
      in birds prefed the high protein diet and nitrogen loss was lower in birds prefed
      the low protein diet.

PMID- 1358512
TI  - Gut microflora can modify fatty acid composition in liver and egg yolk lipids of
      laying Japanese quail (Coturnix coturnix japonica).
AB  - 1. The influence of the gut microflora on lipid metabolism was investigated in
      germ-free (GF) and conventional (CV) laying Japanese quail. 2. Serum and egg yolk
      cholesterol concentrations showed comparable values in both GF and CV
      environments. 3. The fatty acid composition of liver lipids was modified by the
      presence of gut microflora. Notably, in the presence of the gut microflora,
      proportion of oleic acid was reduced and conversely, stearic and linoleic acids
      were enhanced. 4. In egg yolk lipids, the proportion of myristoleic and
      palmitoleic acids was significantly lowered and that of stearic acid was
      significantly enhanced by the presence of the gut microflora, though the
      difference was very small. 5. It was suggested that oleic acid could be easily
      either hydrogenated to stearic acid or desaturated to linoleic acid by the action
      of the gut microflora in Japanese quail.

PMID- 1358513
TI  - Comparison of fibre digestion and digesta retention time between nutrias
      (Myocaster coypus) and guinea-pigs (Cavia porcellus).
AB  - 1. Digestibilities of feed, and transit and retention time of fluid and particle
      digesta marker measured in nutrias (Myocaster coypus) and guinea-pigs (Cavia
      porcellus) fed on a diet containing 50% alfalfa. 2. The digestibility of fibre
      was higher in the nutria, along with the longer retention time of digesta. 3. The
      liquid and particle marker were similarly excreted, suggesting no separation
      mechanism in the gastrointestinal tract of both the animals. 4. The apparent
      digestibility of protein in the nutria was superior to the guinea-pig and other
      small hindgut fermenters, suggesting that the contribution of coprophagy on
      protein nutrition of nutrias is significant.

PMID- 1358514
TI  - Comparative effects of the water accommodated fraction of three oils on mussels.
      1. Survival, growth and gonad development.
AB  - 1. Mussels, Mytilus galloprovincialis, were exposed to the water accommodated
      fraction (WAF) of two crude oils (types Ural and Maya) and of a commercial
      lubricant oil for 91 days. Synchronous spectrofluorometry showed that the
      aromatic hydrocarbon composition of the WAFs obtained from the three oils were
      significantly different (Maya-WAF heaviest, Ural-WAF lightest). 2. No significant
      mortality occurred in mussels exposed to the WAFs of the two crude oils, while
      all the animals exposed to lubricant-WAF died after 49 and 77 days in
      intermediate and high doses respectively. 3. Flesh and shell growth of mussels
      exposed to the WAFs was reduced significantly with respect to controls as
      demonstrated by several size, condition and allometric parameters. The response
      to petroleum hydrocarbon exposure is not dose-dependent, maximal responses being
      measured in low (Ural) and intermediate (Maya) doses. This seems to depend on a
      behavioural reaction (shell valve closure) against high doses of pollutants which
      may avoid the sublethal damage to some extent. 4. Shell abnormalities or changes
      in shell thickness were not detected. 5. The histological study of gonad tissue
      revealed that gamete release is retarded and hemocytic infiltration of mature
      gonad tissue is increased after exposure to low and intermediate doses of the
      WAFs. On the other hand, spawning is readily induced under exposure to high doses
      of the WAFs.

PMID- 1358515
TI  - Comparative effects of the water accommodated fraction of three oils on mussels.
      2. Quantitative alterations in the structure of the digestive tubules.
AB  - 1. Mussels have been exposed to the water accommodated fraction (WAF) of Ural and
      Maya crude oils and of a lubricant oil for 91 days and the digestive gland
      structure has been studied (a) by planimetry, to calculate the mean epithelial
      thickness (MET), the mean diverticular radius (MDR) and the mean luminal radius
      (MLR) of the digestive tubules and (b) by subjective tubule grading, to determine
      the relative (%) occurrence of the different tubule types found in the digestive
      gland (holding, absorpting, disintegrating, reconstituting and necrotic tubules).
      2. Exposure to the 3 types of WAF leads to lowered MET and MET/MDR values, and
      concomitant higher MLR/MET values. In the case of lubricant- and Ural-WAF
      exposures, MDR decreases significantly at increasing exposure-doses. 3. Exposure
      to oil WAFs leads to decreased percentages of holding and absorpting tubules.
      This decrease is concomitant with an increase of disintegrating tubules in
      lubricant- and Ural-WAF exposures, and with an increase of regenerating tubules
      in the Maya-WAF exposure. 4. The statistical significance of the differences
      found between control and exposed mussels is better at Day 21 than at any other
      further sampling day (35, 77 and 91). 5. Multiple correlation coefficients
      between all the percentages of tubule types and each planimetric parameter
      present an excellent statistical significance.

PMID- 1358516
TI  - The involvement of collagenase in the necrosis induced by the bites of some
      spiders.
AB  - 1. The midgut extracts of 13 Australian spider species produced cellular
      disruption in mouse skin in tissue culture conditions. 2. Microbial collagenase
      and the venoms of some of these species had similar effects. 3. Five venoms also
      caused severe dermonecrosis in living mice. 4. Pre-mixing the venoms with L
      cysteine caused complete in vivo and partial in vitro inhibition of their
      effects. 5. It was concluded that collagenase is a major factor in the aetiology
      of necrotic arachnidism.

PMID- 1358517
TI  - Mouse and rat strain variations in sensitivity to N-nitroso-diethylamine,
      hereditary transmission of the trait and the effect of 3-tert-butyl-4
      hydroxyanisole on sensitivity.
AB  - 1. Strain variations among male mice were studied in terms of the number of days
      of survival with chronic administration of N-nitroso-diethylamine (NDEA). Four
      inbred strains, two F1 progenies and one F2 progeny were tested. 2. BALB/c mice
      survived for the longest period, whereas C3H mice survived for the shortest time.
      Results of examinations of BALB/c-C3H-F1, -F2 and C57BL-CBA-F1 mice revealed that
      the hereditary trait could be adequately explained by postulating two loci of
      genes or gene clusters that regulate the sensitivity to NDEA. 3. Simultaneous
      chronic administration of 3-tert-butyl-4-hydroxyanisole (BHA) could prolong the
      survival period. 4. Preliminary histopathological examinations of the liver
      tissues revealed that the lesion at the time of death of the mice varied
      considerably depending on the strain and the length of survival. Evidence for
      hereditary transmission of the characteristics of histopathological changes,
      including development of liver hemangiosarcoma, is presented. 5. The strain
      variations among male and female rats were also studied in terms of the number of
      days of survival with chronic administration of NDEA. Five strains and one F1
      progeny were tested. 6. From these and previous observations, the possible
      biochemical factors determining sensitivity to NDEA were discussed.

PMID- 1358519
TI  - The effects of acetylcholine, dopamine and noradrenaline on the visceral ganglion
      of Helix pomatia. I. Ongoing compound field potentials of low frequencies.
AB  - 1. The question was addressed what effects do some neurotransmitters exert upon
      the ongoing compound activity of an organized invertebrate ganglion, such as the
      visceral ganglion of the gastropod mollusc, Helix, recorded with extracellular
      semimicroelectrodes in the neuropile, avoiding dominating single units. 2.
      Methods of analysis based on systems theory are used: the electrical activity of
      the snail brain is considered to be a summation of different measurable variables
      or subsystems (in this case, "frequency components"). Frequency components were
      analyzed by the Fourier transform and, for quantification of each component, root
      mean-square (RMS)-voltage of digitally filtered signals. 3. Spontaneous discharge
      of the untreated ganglion shows RMS-voltage of less than 10 microV in the 1-50 Hz
      range, most frequently 3-7 microV. Energy extended far above 50 Hz, with less
      decline than in vertebrates, but was quantified only up to 80 Hz due to the wider
      fluctuations of RMS-voltage in the range greater than 50 Hz. 4. ACh (10(-5)-10(
      3) M) induces strong, dose-related increase of activity with spontaneous
      frequency responses in a broad band between 2 and 20 Hz which accompany
      fluctuations of minor peakings frequently centering at 2-4, 4-8, 9-15 and 20 Hz.
      These frequency centers still remain but as an impression since a statistical
      study on the reality and position of the peaks has not yet been done. ACh-induced
      excitation seems to be rather transient: all frequency components except the 4-8
      Hz component decrease within 4-6 min. 5. DA (10(-4)-10(-3) M) induces a dose
      related increase in the low frequency range (1-15 Hz) which reaches a maximum
      within 4 min and remains relatively unchanged for as long as 10 min. 6. NA (10(
      5)-10(-2) M) mainly depresses the ganglionic activity, though moderately,
      reducing all components (-25%). The action of NA on the Helix ganglion seems to
      incline more towards inhibition of firing than towards excitation, especially
      depressing the 15-48 Hz activity, whereas that on the mammalian brain is known to
      be enhancement of alpha (8-13 Hz)- and beta (15-30 Hz)-activities. 7. The
      activities observed in the present investigation at several lower frequency power
      peaks are also commonly found in the electrograms of vertebrates and the EEG of
      higher animals. The manner, in which ACh and DA influence these peaks in Helix
      pomatia, are very similar to what has been reported on the EEG of
      mammals.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1358518
TI  - Cyclophosphamide and its metabolite acrolein. Some studies on their
      porphyrinogenic action in 17 day old chick embryo.
AB  - 1. Some studies of cyclophosphamide (CP) and its metabolite acrolein in chick
      embryo liver were carried out in order to investigate the mechanism of the
      porphyrinogenic action of CP. 2. In vitro and in vivo studies revealed that CP
      induced but did not activate delta-aminolaevulinic acid (ALA) synthase. 3.
      Pretreatments with phenobarbital (PB) or SKF-525A did not modify ALA-synthase
      induction produced by CP. 4. Acrolein administration neither induced ALA-synthase
      activity nor increased cytochrome P-450 content or led to hepatic porphyrin
      accumulation. 5. Time course induction of cytochrome P-450 content after
      administration of CP or PB was similar. 6. The results obtained would indicate
      that CP is a strong inducer of both ALA-synthase activity and microsomal
      cytochrome P-450 content in liver of 17 day-old chick embryos and that its
      porphyrinogenic activity is not mediated by its metabolite acrolein.

PMID- 1358520
TI  - The effects of acetylcholine, dopamine and noradrenaline on the visceral ganglion
      of Helix pomatia. II. Stimulus evoked field potentials.
AB  - 1. Neurophysiological effects of acetylcholine (ACh), dopamine (DA) and
      noradrenaline (NA) on stimulus evoked field potentials in the Helix pomatia
      visceral ganglion were investigated. Electrical stimuli were applied to nerve
      trunks. 2. For frequency analysis of evoked potentials (EPs) the Fourier
      transform was performed. For quantification of pre- as well as poststimulus
      activities, root-mean-square (RMS)-voltages of digitally filtered signals were
      used. 3. ACh at 10(-4)-10(-3) M selectively enhances the 4-15 Hz as well as the
      30-70 Hz components and DA at 10(-5)-10(-3) M increases the 30-70 Hz activity. NA
      at 10(-5)-10(-4) M augments the 15-30 Hz response and only at 10(-5) M increases
      the 30-48 Hz response. 4. All transmitters at 10(-2) M show a strong tendency to
      suppression. 5. Prestimulus activities of ACh and DA are damped by 40-50%
      compared to the ongoing induced activities in the non-stimulus study (cf. Part
      I). These damped prestimulus activities may be considered as a late part of the
      prolonged evoked activity. 6. The 4-15, 15-30 and 30-70 Hz responses selectively
      increased by the transmitters may be compared to theta-alpha combined rhythm,
      beta-rhythm and 40 Hz rhythm in the mammalian EEG.

PMID- 1358521
TI  - Dopamine inhibits transmission between the interneuron initiating pacemaker
      activity in a bursting neuron and the bursting neuron on the snail Helix pomatia.
AB  - 1. The effect of external application of dopamine on connection between a
      peptidergic interneuron initiating bursting pacemaker activity in non-active
      burster RPa1 and the bursting neuron itself of the snail Helix pomatia has been
      investigated under clamp conditions. 2. External application of dopamine in a
      dose-dependent manner (Kd 15 microM) produces a reversible inhibition of slow
      inward current (SIC) in the RPa1 neuron evoked by stimulation of peptidergic
      interneuron. At the same time, an increase of duration and amplitude of
      interneuronal action potential was observed. 3. Stimulation of the anal nerve
      evokes in RPa1 neuron postsynaptic current consisting of at least three
      components: two fast ones with reversal potentials -50 and -70 mV and a long
      lasting one with no reversal potential between -50 and -95 mV. 4. It is concluded
      that inhibition of SIC by dopamine is due to the processes occurring in the
      postsynaptic RPa1 neuron. 5. Based on the hypothesis that bursting activity of
      RPa1 neuron results from the activation of presynaptic unidentified peptidergic
      interneuron(s) with persistent activity and on data presented it is suggested
      that inhibition of bursting activity evoked by application of dopamine or anal
      nerve stimulation is a consequence of decreased efficiency of synaptic
      transmission between the interneuron initiating bursting activity and the
      burster.

PMID- 1358522
TI  - In vivo neurotoxin administration alters immune responses in chickens (Gallus
      domesticus).
AB  - 1. 6-Hydroxydopamine (6-OHDA) administered in ovo enhanced in primary immune
      response to sheep red blood cells (SRBC) in chicks 2. Splenic norepinephrine
      levels increased during the peak anti-SRBC response. 3. Cell-mediated immunity as
      measured by delayed-type hypersensitivity to phytohemagglutinin-P (PHA-P) was not
      affected by treatment with 6-OHDA.

PMID- 1358523
TI  - Contractile responses to electrical field stimulation and ATP in guinea-pig
      urinary bladder.
AB  - 1. The responses of guinea-pig urinary bladder smooth muscle to intramuscular
      nerve stimulation were investigated by isometric tension recording. 2. The nerve
      mediated contractions, evoked by field stimulation with a stimulus of 0.5 msec
      duration, a frequency of 15 Hz and a voltage of 50 V, were inhibited by atropine
      (10(-6) M) and alpha, beta-MeATP (10(-4) M) to about 80% and 20%, respectively,
      of control. 3. Simultaneous application of atropine (10(-6) M) and alpha, beta
      MeATP (10(-4) M) abolished the contraction evoked by selective nerve stimulation.
      4. Terodiline (10(-4) M), one of Ca2+ antagonists, inhibited the contraction
      evoked by both nerve selective stimulation and exogenously applied ATP. 5. Based
      on these results we suggested that in guinea-pig urinary bladder, ATP was a
      predominant excitatory transmitter and the nerve-mediated contraction and
      exogenous ATP were mainly dependent upon Ca2+ influx.

PMID- 1358524
TI  - Effect of Galleria mellonella larvae preparation and honeybee products on cell
      cultures.
AB  - 1. The action of the extract from larvae of the great wax moth Galleria
      mellonella L. used in Russian folk medicine was studied. 2. Two active components
      influencing the growth and morphological differentiation of cells in vitro were
      found. 3. The presence of these components in the extract was conditioned by
      consumption of honeybee products by Galleria mellonella larvae. 4. Cytotoxicity
      of honeybee products was studied.

PMID- 1358525
TI  - Inhibition of the transepithelial potential difference and short circuit current
      in the isolated frog skin by alloxan.
AB  - 1. Electrical parameters: short circuit current (SCC), transepithelial potential
      difference (PD) and electrical resistance (R) were measured in isolated frog skin
      (Rana pipiens) in the presence and in the absence of alloxan. 2. Alloxan
      decreased SCC and PD in a concentration-dependent pattern, while R remained
      unchanged. 3. The effect on SCC and PD was observed after 25 min of exposure to
      the drug. Maximal average effect was 20% in SCC and 17.5% in PD. 4. These results
      suggest that alloxan decreased epithelial sodium transport, through interference
      with the activity of the Na(+)-K(+)-ATPase.

PMID- 1358526
TI  - Histamine activates whole cell K+ currents in swine carotid arterial smooth
      muscle cell.
AB  - 1. The effects of histamine on whole cell K+ currents were evaluated in cultured
      smooth muscle cells that were derived from explants of swine carotid artery.
      These cells exhibited cytoplasmic protein and agonist-induced calcium responses
      typical of noncultured smooth muscle cells. 2. Upon obtaining whole cell
      configuration, depolarization from a holding potential of -80 mV elicited a
      slowly inactivating voltage-dependent outward current that was sensitive to
      tetraethylammonium and 4-aminopyridine. 3. These K+ currents were at least
      partially Ca2+ dependent since they were inhibited by extracellular bath
      application of verapamil or by substitution of external Ca2+ with Co2+. 4. The
      addition of extracellular histamine increased the outward current both in the
      presence and absence of extracellular Ca2+ and this response was blocked by (+/
      )chlorpheniramine. 5. We conclude that swine carotid arterial smooth muscle cells
      exhibit voltage and calcium dependent potassium current and that these currents
      are modified by histamine stimulation.

PMID- 1358527
TI  - Lead retards development of Drosophila melanogaster.
AB  - 1. Lead (Pb) is a ubiquitous environmental toxicant which has been reported to
      have growth-retarding effects. That premise was examined in the current study of
      the effects of developmental exposure to Pb on the maturation of the fruitfly
      Drosophila melanogaster. 2. Flies were raised from egg to adulthood in media to
      which 0, 100, 250, or 500 ppm Pb acetate added. 3. There was a dose-dependent
      delay of maturation but no apparent effect on survival to adulthood. There were
      no significant differences in this effect between male and female flies. 4.
      Weights of fly offspring and their fecundity were not related to increasing
      exposure levels, suggesting that the delays were not due to gross nutritional
      deficits. 5. Analyses of Pb content indicated exposure-dependent body burdens of
      Pb in flies. Timed analyses of the Pb content of media itself indicated a
      heterogeneous distribution of Pb in the media, suggesting some precipitation of
      Pb at the highest exposure, occurring primarily during the first hour. 6. The
      mechanistic bases of the Pb-induced retardation of D. melanogaster development
      remain unknown, but it is concluded that because of the extensive body of
      knowledge on D. melanogaster genetics, molecular biology, and developmental
      biology, this procedure could serve as a model system for further study of the
      developmental consequences of exposure to Pb or other toxicants. 7. Environmental
      Pb exposure resulting in retarded development could have deleterious
      repercussions for insect populations exposed chronically to high levels of Pb.

PMID- 1358528
TI  - Bioactive substances in nerve-cord extracts from an echiuroid, Urechis unicinctus
      -II. Peptidic substances.
AB  - 1. Two peptides that showed an inhibitory effect on twitch contraction of the
      inner circular body-wall muscle of the echiuroid Urechis unicinctus were purified
      from extracts of the ventral nerve cords of the worms. 2. On the basis of the
      results of amino acid analysis, amino acid sequence analysis and FAB-MS
      measurement, the primary structures of the peptides were proposed to be H-Phe-Arg
      Val-Phe-OH (FRVF) and H-Phe-Arg-Phe-OH (FRF). 3. FRVF and FRF were synthesized,
      and their behavior on HPLC and biological activities on the body-wall muscle were
      confirmed to be identical to those of the native peptides. 4. FRVF was also found
      to have a potentiating effect on spontaneous contractions of the intestine of the
      African clawed toad Xenopus laevis.

PMID- 1358529
TI  - The comparison of the effects of heavy metal ions on the antioxidant enzyme
      activities in human and fish Dicentrarchus labrax erythrocytes.
AB  - 1. The effect of the increasing concentrations of CuSO4 and HgCl2 (0.01-0.3
      mmol/l) on erythrocyte haemolysis and the activities of peroxide metabolism
      enzymes: superoxide dismutase, catalase, peroxidase and glutathione peroxidase
      was investigated in human erythrocytes and the nucleated red blood cells of
      marine fish (Dicentrarchus labrax). 2. The results show that both heavy metal
      ions had only little effect on haemolysis and antioxidant enzyme activities in
      human erythrocytes; in contrast the effect of heavy metals on fish erythrocytes
      was statistically significant when compared to control values. 3. Copper was
      found to have more pronounced effect than mercury on the erythrocytes of
      Dicentrarchus labrax; otherwise there were no significant differences between the
      toxic effects of both ions on human erythrocytes. 4. We suggest that the
      mechanism of copper-induced haemolysis may be different from that of mercuric ion
      in the erythrocytes of Dicentrarchus labrax.

PMID- 1358531
TI  - Separation of cytochrome P-450 containing vesicles from the midgut microsomal
      fraction of Manduca sexta.
AB  - 1. Microsomes prepared from midgut tissue of Manduca sexta by differential
      centrifugation are a heterogeneous population of vesicles. 2. Upon centrifugation
      of microsomes in a sucrose gradient of 30%, 15% and 10%, specific activity of
      cytochrome P-450 catalyzed O-demethylation of p-nitroanisole (a marker enzyme for
      endoplasmic reticulum) was increased 2.5 to 3.5-fold in the 15% fraction. 3.
      Specific activities of alkaline phosphatase and leucine aminopeptidase (marker
      enzymes for brush border membranes) were increased 3.1 to 5.7-fold in the pellet.
      4. Differential centrifugation is a useful step in the purification of cytochrome
      P-450 enzymes.

PMID- 1358530
TI  - Effect of local hyperthermia and chemotherapy on MC29 virus-induced liver tumor
      transplanted into subcutis of chickens.
AB  - 1. A transplantable liver tumor induced by MC29 virus, whose specific utilization
      of glutamine in growth of the tumor had been well-demonstrated, was implanted in
      the subcutis of day-old chickens, and after 7-8 days, when the tumor had reached
      a soybean size, local hyperthermia with microwave and/or chemotherapy with 6
      diazo-5-oxo-1-norleucine (DON), an inhibitor of glutamine metabolism, were given
      once a day for 7 days successively. 2. At the 7th day of experiment, the tumor
      growth ratio, expressed by mean +/- standard deviation was, in the tumor control
      group, 14.3 +/- 1.81; in DON group, 6.93 +/- 0.95; in local hyperthermia group,
      3.24 +/- 2.25, and in DON+hyperthermia group, 0.61 +/- 0.57. 3. The body weight
      gain ratio in the local hyperthermia group was evidently higher than that in the
      tumor control group. DON suppressed body weight gain most remarkably. 4. In the
      present transplantable tumor system, microwave local hyperthermia was more
      effective in tumor suppression and less hazardous to the host than our former
      whole-body hyperthermia.

PMID- 1358532
TI  - Amine oxidase enzymes of sheep blood vessels and blood plasma: a comparison of
      their properties.
AB  - 1. A comparison between the biochemical properties of semicarbazide-sensitive
      amine oxidase (SSAO) activities has been made in sheep blood plasma and arterial
      wall. 2. The metabolism of benzylamine (BZ) by blood plasma was resolved into
      high affinity (Km 2.76 +/- 0.24 microM) and low affinity (Km 743 +/- 49 microM)
      activities. Spermidine metabolism was by a single component (Km 174 +/- 22
      microM) and this amine reduced the metabolism of high concentrations of BZ. 3. A
      single component metabolised BZ in arterial homogenates (Km 11.3 +/- 1.3 microM)
      and which metabolised spermidine at a very slow rate. 4. Dopamine was deaminated
      by plasma SSAO and competed with both low and high concentrations of BZ. Dopamine
      also interfered with arterial metabolism of BZ. 5. These results suggest that
      there are two SSAO enzymes in sheep blood plasma, with one having similar
      properties to SSAO in the arterial wall.

PMID- 1358533
TI  - The FMRFamide-related decapeptide of Mytilus contains a D-amino acid residue.
AB  - 1. An FMRFamide-related decapeptide isolated from the anterior byssus retractor
      muscle (ABRM) of the bivalve mollusc, Mytilus edulis, was shown to have D-Leu as
      the second amino acid residue. 2. The excitatory effects of the peptide (Mytilus
      FFRFamide) on the ABRM were not changed appreciably by substituting an L-Leu
      residue for the D-Leu residue.

PMID- 1358534
TI  - Neuroactive peptides with an RFamide or Famide carboxyl terminal.

PMID- 1358535
TI  - Haematological effects of vanadium on living organisms.
AB  - Although vanadium has been of great interest for many researchers over a number
      of years, its biochemical and physiological role is not yet fully clear. There
      are many papers describing the haematological consequences of its excess in
      living organisms and most of their data are quoted in this mini-review. The
      authors of these papers used various laboratory animals, different vanadium
      compounds, frequently different routes of administration and duration of
      intoxication. Hence a checklist and comparison of the results are rather
      difficult. Vanadium reduces the deformability of erythrocytes, and such cells are
      rather frequently retained in the reticuloendothelial system of the spleen and
      eliminated faster from the blood stream (Kogawa et al., 1976). Vanadium produces
      peroxidative changes in the erythrocyte membrane, this leading to haemolysis.
      Therefore, the depressed erythrocyte count in animals intoxicated with vanadium
      may be the consequence of both the haemolytic action of vanadium and the
      shortened time of survival of erythrocytes. Changes of the haem precursor level
      in blood serum and urine observed in humans exposed occupationally to vanadium
      suggest an influence of this element on haem synthesis. This problem requires,
      however, further studies and observations. Changes occurring under the influence
      of vanadium on the leukocyte system of animals suggest the influence of this
      element on the resistance of the organism, but the mechanism of the action of
      vanadium still requires elucidation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358536
TI  - Adrenergic mechanisms associated with the movement of platelets in iridophores
      from the freshwater goby, Odontobutis obscura.
AB  - 1. Cultured iridophores from the freshwater goby, Odontobutis obscura, were used
      to investigate adrenergic mechanisms of movement of platelets in the iridophores.
      2. Norepinephrine, which was assumed to be the transmitter of the iridophore
      nerves, induced dispersion of platelets within the cells. 3. The effect of
      norepinephrine was inhibited by an alpha-adrenergic antagonist, yohimbine, but
      not by a beta-adrenergic antagonist, propranolol. 4. Isoproterenol, a beta
      adrenergic agonist, failed to bring about aggregation of platelets. 5. Forskolin,
      an activator of adenylate cyclase, was effective in inducing aggregation of
      platelets. 6. 8-Br-cAMP caused the aggregation of platelets and inhibited the
      norepinephrine-induced dispersion of platelets. 7. It appears that the
      adrenoceptors of the iridophores of this species are solely of the alpha type;
      they mediate the dispersion of platelets; and an increase in intracellular levels
      of cAMP induces the aggregation of platelets.

PMID- 1358537
TI  - Isolation, primary structure and synthesis of neomyosuppressin, a myoinhibiting
      neuropeptide from the grey fleshfly, Neobellieria bullata.
AB  - 1. An amidated decapeptide, showing strong inhibitory activity of spontaneous
      visceral muscle movement was isolated, from head extracts of 42 thousand
      fleshflies, Neobellieria bullata (Diptera, Sarcophagidae). 2. Amino acid
      sequencing and verification by peptide synthesis revealed the following primary
      structure: Thr-Asp-Val-Asp-His-Val-Phe-Leu-Arg-PheNH2. 3. The novel peptide was
      termed neomyosuppressin or Neb-MS. 4. During the process of consecutive high
      performance liquid chromatography (HPLC) purifications the biological activity of
      the samples was monitored using heterologous bioassay system. 5. The threshold
      level of synthetic Neb-MS was found to be 8.6 +/- 0.5 x 10(-11) M on the
      Leucophaea hindgut and 3.4 +/- 0.5 x 10(-10) M on the Locusta oviduct bioassay,
      respectively.

PMID- 1358538
TI  - Changes in biochemical composition of gills, hepatopancreas and muscle of the red
      crayfish Procambarus clarkii (Girard) after sublethal exposure to mercury.
AB  - 1. The changes in the biochemical composition of gills, hepatopancreas and muscle
      after exposure to 0.25 mg Hg/l were studied in Procambarus clarkii. 2. Sublethal
      exposure to mercury in P. clarkii resulted in significant decreases in protein
      concentration and caloric concentration in gills over the 96 hr period.
      Glycogen/lipid and glycogen/protein ratios increased after 48 and 96 hr of
      mercury exposure. 3. Lipid and caloric concentration in the hepatopancreas were
      significantly lower in 96 hr mercury exposed group. 4. Glycogen concentration in
      muscle was depleted as consequence of 96 hr mercury exposure.

PMID- 1358540
TI  - Inhibition of dipteran larval neuromuscular synaptic transmission by analogues of
      philanthotoxin-4.3.3: a structure-activity study.
AB  - 1. The blocking action of delta-philanthotoxin (PhTX-4.3.3), a wasp toxin
      composed of a polyamine chain, an aromatic amino acid (tyrosyl) nucleus and an
      aliphatic (butanoic) acid was studied, together with 33 structural analogues, at
      the glutamatergic neuromuscular synapse in larvae of the house fly, Musca
      domestica. 2. Shortening of the polyamine or the aliphatic acid chain, or
      removing the aromatic nucleus caused a decrease in potency. 3. An increase in
      potency was obtained by elongating the molecule in any of several directions:
      elongation of the polyamine chain with amine containing groups, by iodination of
      the aromatic moiety and by aliphatic or aromatic elongation of the butanoic acid.

PMID- 1358539
TI  - Initial characterization of the organophosphate acid anhydrase activity of the
      chicken, Gallus domesticus.
AB  - 1. Supernatant solutions from kidney and liver homogenates of the chicken, Gallus
      domesticus, were found to hydrolyze the organophosphate (OP) compound
      diisopropylfluorophosphate (DFP). The activity on DFP as substrate was heat
      inactivated and was characterized for temperature and pH optima, enzyme kinetics,
      and requirements for manganous ion. 2. Gel column chromatography indicated that
      the DFPase in both tissues is in the range of 82,100 to 93,300 D. This activity
      is strongly inhibited by N,N'-diisopropylphosphorodia-midofluoridate (mipafox).
      3. The chicken has organophosphate acid (OPA) anhydrase activity comparable to
      other eucaryotic sources in its ability to hydrolyze DFP. Although birds may not
      have paraoxonase activity comparable to mammalian species, they do not differ
      significantly in the ability to hydrolyze DFP and probably related compounds.

PMID- 1358541
TI  - Some pharmacological properties of the oviduct muscularis of the stable fly
      Stomoxys calcitrans.
AB  - 1. Spontaneous and rhythmic contractions were measured in 80% of the preparations
      of the stable fly oviduct which were separated from the central nervous system
      and other tissues. Measurements of the changes in the amplitude and frequency of
      contractions and changes in the baseline tonus were taken separately, even though
      they often occurred together during chemical treatments. 2. L-glutamate, at a
      concentration of 10(-4) to 10(-3) M, caused an increase in the frequency of
      contractions and in muscle tonus. Contraction frequency showed the highest
      percentage of change while amplitude and tonus had lower values. 3. The
      excitation threshold for proctolin on the oviduct was between 10(-13) and 10(-10)
      M. The initial responses to the peptide showed increases in the amplitude,
      frequency, and tonus of muscle contractions. However, tonic changes dominated the
      response profile when the concentration reached 10(-10) or 10(-9) M. In 12
      experiments in which the oviduct was exposed to 10(-7) M leucomyosuppressin, no
      change in the amplitude, frequency, or tonus of muscle contractions was detected.
      4. Octopamine caused an inhibition of spontaneous muscle contractions of the
      oviduct. Spontaneous contractions showed a graded drop in activity over the
      concentration range tested (10(-8)-10(-6) M). Also 57% of the preparations tested
      showed a substantial drop in baseline tonus after the addition of octopamine. 5.
      Stable fly oviducts exposed to extracts from the male reproductive tract showed a
      noticeable change in the amplitude frequency and tonus of muscle contraction at
      levels of 2 to 3 equivalents.

PMID- 1358543
TI  - Oxygen consumption and ammonia-N excretion of Penaeus chinensis juveniles exposed
      to ambient ammonia at different salinity levels.
AB  - 1. Oxygen consumption rate (O2 mg/g/hr) and ammonia-N (un-ionized plus ionized
      ammonia as nitrogen) excretion rate (microgram/g/hr) of Penaeus chinensis
      juveniles (0.54 +/- 0.11 g) decreased with increase of salinity among 10, 20 and
      30 ppt. 2. Oxygen consumption rate increased with increase of ambient ammonia-N
      at three salinity levels. 3. Ammonia-N excretion rate was highest (204
      micrograms/g/hr) in P. chinensis exposed to 0.985 mg/l ammonia-N at 10 ppt, and
      lowest (-416 micrograms/g/hr) in that exposed to 9.897 mg/l ammonia-N at 30 ppt.
      4. In the prawns exposed to 9.921 mg/l ammonia-N at 20 ppt, and to 5.087 and
      9.897 mg/l ammonia-N at 30 ppt, ammonia-N excretion was heavily depressed and
      ammonia-N influx occurred (ammonia-N uptake was much higher than ammonia-N
      excretion).

PMID- 1358542
TI  - Effect of acrylamide monomer on hepatic CYP1A1 monooxygenase induction in rainbow
      trout.
AB  - 1. Rainbow trout hepatic microsomes were pre-incubated in vitro with 1 pM, 1 nM,
      and 1 microM acrylamide for 20 or 30 min and ethoxyresorufin-O-deethylase (EROD)
      was measured. In vitro pre-incubation did not produce a significant decrease in
      EROD catalytic activity. 2. The effects of 50 ppm acrylamide monomer on hepatic
      CYP1A1 mRNA and CYP1A1 isozyme steady state levels in rainbow trout were
      determined after 6, 10, and 14 days of exposure. 3. Acrylamide monomer produced a
      35% increase, 51% decrease and 140% increase in CYP1A1 mRNA at 6, 10 and 14 days,
      respectively, while at the same time CYP1A1 isozyme levels were decreased 12%,
      67%, and 62% and EROD activity was decreased 33%, 90%, and 86%, respectively. 4.
      This indicates that acrylamide treatment may result in either a change in the
      translation of CYP1A1 mRNA or an isozyme selective inactivation of CYP1A1
      resulting in loss of CYP1A1 apoprotein. 5. The effect of acrylamide treatment on
      hepatic CYP1A1 induction was determined using 10 or 14 day treatment with 50 ppm
      acrylamide monomer in a flowthrough exposure and induction with beta
      naphthoflavone (beta-NF; 100 mg/kg i.p.) for 1 or 4 days. 6. Acrylamide and 1-day
      beta-NF had no effect on CYP1A1 mRNA levels when compared to 1-day beta-NF
      treatment alone, but acrylamide and 4-day beta-NF resulted in a 74% decrease in
      CYP1A1 mRNA compared to 4-day beta-NF treatment alone.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1358545
TI  - The actions of phorbol esters upon isolated calcium currents of Helix aspersa
      neurones.
AB  - 1. Voltage-clamp recordings have been made from identified neurones in the
      suboesophageal ganglia of Helix aspersa. 2. Calcium currents were isolated
      pharmacologically and studied under two-electrode voltage-clamp. 3. PdBu but not
      PMA caused a transient enhancement followed by an irreversible inhibition of the
      calcium current. 4. It is concluded that activation of protein kinase C within
      these neurones may show selectivity with respect to the exogenous activator used.

PMID- 1358544
TI  - A comparative study on the effects of diethyl ether and thiopentone sodium on
      plasma catecholamine levels in the rat.
AB  - 1. The primary aim of this investigation was to ascertain the effects of
      thiopentone sodium and diethyl ether as anaesthetics on plasma catecholamine
      levels of Sprague-Dawley and Long-Evans rats. A secondary aim was to investigate
      the effect of norepinephrine on susceptibility to electrically induced arrhythmia
      in the Langendorff perfused isolated rat heart. 2. Thiopentone sodium anaesthesia
      resulted in significantly lower plasma norepinephrine and epinephrine levels when
      compared with diethyl ether anaesthesia. 3. Long-Evans rats exhibited
      significantly higher epinephrine levels regarding both anaesthetics in comparison
      with their Sprague-Dawley counterparts. 4. If plasma catecholamines are an
      indicator of the level of induced stress then diethyl ether anaesthesia resulted
      in more stress both of a psychological and physiological origin when compared
      with thiopentone sodium anaesthesia. 5. Long-Evans rats seem to be more prone to
      the physiologically-induced component of stress than Sprague-Dawley rats. 6. In
      isolated hearts, norepinephrine increased susceptibility (P less than 0.002) to
      electrically induced arrhythmia. This occurred at a concentration corresponding
      to measured upper levels of total catecholamines in diethyl ether anaesthetised
      animals.

PMID- 1358546
TI  - Cardiac activity of calcitonin gene-related peptide in amphibian species (Rana
      tigrina, Triturus sp).
AB  - 1. Calcitonin gene-related peptide (CGRP) produced dose-related positive
      chronotropic and inotropic responses in isolated atria of a newt, Triturus sp.
      and a frog, Rana tigrina. It was apparent that CGRP was stimulatory on the heart
      of the amphibian species. 2. In the frog, these dose-related responses were
      attenuated in the presence of a CGRP antagonist (hCGRP 3 x 10(-8) M). This was
      indicative of the presence of cardiac CGRP receptors. 3. In the presence of beta
      adrenergic (propranolol 10(-6) M) and calcium channel (verapamil 10(-8) M, but
      not nifedipine 10(-8) M) blocker, the basal AR in the frog were decreased. AR
      induced by CGRP were increased however. 4. The maximal AR and AT responses of the
      isolated atria to CGRP were not affected by the presence of propranolol. 5. In
      the presence of calcium channel blockers (verapamil and nifedipine), the maximal
      AT response was attenuated. These changes suggest the cardiac effects of CGRP are
      related to calcium mobilization.

PMID- 1358547
TI  - Resumption of testicular activity in Gobius paganellus after administration of
      ethane 1,2-dimethane sulfonate (EDS).
AB  - 1. The effect of a single injection of ethane-1,2-dimethane sulfonate (EDS) was
      studied in the teleost fish, Gobius paganellus in two different periods of the
      year. 2. During June EDS did not induce any change, while during December the
      drug was highly effective in promoting testicular activity. 3. Nucleus/cytoplasm
      ratio of interstitial cells strongly decreased concomitantly with the detection
      of high testicular androgen levels. 4. The germinal compartment was well
      developed showing the appearance of all spermatogenic stages and the cavity of
      lobular compartments filled of spermatozoa. 5. Our data are the first evidence of
      a stimulatory activity of EDS on testes of a vertebrate species.

PMID- 1358548
TI  - Effects of copper, iron and zinc on oedema formation induced by phospholipase A2.
AB  - 1. Intradermal or subplantar injection of soluble snake venom phospholipase A2
      (PLA2) evoked a brisk inflammatory response, with cutaneous vascular permeability
      increase and paw oedema. 2. These inflammatory processes are mainly the result of
      arachidonic acid cascade activation and mast cell degranulation. 3. Copper, iron
      and zinc have an inhibitory effect on vascular permeability increase and paw
      oedema induced by PLA2. 4. Copper and iron could have not only a direct effect on
      PLA2 but on enzymes of arachidonic acid cascade. 5. However, zinc have a moderate
      antiinflammatory activity. This effect could be the result to inhibit PLA2
      induced mast cell degranulation.

PMID- 1358549
TI  - Gender influences the in vitro renin release responses to dopamine and adrenergic
      receptor blockade in the summer-active ground squirrel Spermophilus lateralis.
AB  - 1. 10(-4) M Dopamine stimulated and 10(-7) M inhibited in vitro resting renin
      release (RR) only in the female animals. 2. Alpha- or beta-adrenergic blockade
      prevented the stimulation but not the inhibition of RR by dopamine in the female
      animals. 3. Membrane receptor mechanisms mediating these changes do not involve
      alterations in tissue cyclic AMP content. 4. The sensitivity of the
      juxtaglomerular cells to dopamine challenge is gender dependent during summer
      activity.

PMID- 1358550
TI  - VX enhances neuronal excitability and alters membrane properties of Rana
      catesbeiana sympathetic ganglion neurons.
AB  - 1. The effects of VX (10 microM) were examined on sympathetic ganglion neurons
      from the bullfrog using intracellular recording techniques. 2. VX significantly
      increased the amplitude of the residual EPSP from 4.8 +/- 0.86 mV (n = 4) to 13.7
      +/- 1.23 mV (n = 4). 3. VX significantly decreased the membrane potential 5.2 +/-
      0.75 mV (n = 6). The input resistance and the duration of the spike
      afterhyperpolarization (AHP) were also reduced 69.8% and 69.6% of control,
      respectively. 4. VX increased neuronal excitability greater than 200% (n = 5) of
      control. 5. The VX-induced neuronal excitability may result from a reduction in
      the duration of the AHP and contribute to the CNS toxicity.

PMID- 1358551
TI  - Molecular genetic analysis in autosomal dominant keratoconus.
AB  - Members in three generations of a family whose propositus had keratoconus were
      examined by biomicroscopy, with a corneoscope and a computer-assisted videophoto
      keratoscope. Keratoconus was detected in eight of 15 family members with vertical
      transmission consistent with autosomal dominant inheritance. Affected individuals
      displayed variable topographic features. Abortive "nipple-type" cones were
      identified in some individuals in successive generations using the computer
      assisted videophotokeratoscope and more advanced nipple-type cones detected on
      biomicroscopy of other family members. We selected a COL6A1 cDNA (the gene
      encoding the alpha 1 chain of type VI collagen) as a "candidate gene" to
      determine cosegregation with the disease locus. Linkage analysis excluded a gene
      locus for keratoconus on the most telomeric region of chromosome 21 in this
      family.

PMID- 1358552
TI  - Prolonged paralysis after long-term vecuronium infusion.

PMID- 1358553
TI  - Recent Developments in the Immunopathology of Intraocular Inflammation.
      Proceedings of 2nd international symposium. Aberdeen, Scotland, 22-25 October
      1991.

PMID- 1358554
TI  - Immunopathology and altered immunity in posterior uveitis in man: a review.
AB  - Posterior uveitis is thought to be a T-cell mediated disease since active foci of
      inflammation, identified in eyes enucleated for the complications of intraocular
      inflammation, are found to be predominantly composed of CD4+ T-cells. Few B-cells
      and little immunoglobulin are found suggesting that antibody and immune complex
      deposition do not play a major role in perpetuating the inflammatory process. As
      ocular biopsy is not a feasible method for monitoring disease activity and
      response to treatment, parameters of T-cell activation and retinal damage have
      been studied in the peripheral blood. These have included antibody and T-cell
      sensitisation to retinal S-antigen, serum soluble IL-2 receptors and IL-2
      receptors on activated T-cells. none of these parameters, however, have been
      found to be useful in the monitoring of ocular disease activity alone or in the
      prediction of disease relapse.

PMID- 1358555
TI  - Circulating ICAM-1 levels in serum of uveitis patients.
AB  - Intercellular Adhesion Molecule-1 (ICAM-1) is a cytokine-inducible adhesion
      molecule expressed on cells of multiple lineages at sites of inflammation.
      Recently a truncated form of ICAM-1 has been discovered to be circulating in
      serum. This study reports on circulating serum (cICAM-1) levels in 132 uveitis
      patients (HLA-B 27 pos. acute anterior uveitis (AAU); HLA-B27 neg. anterior
      uveitis (AU); intermediate uveitis (IU); heterochromic cyclitis Fuchs (HCF);
      sarcoidosis; Toxoplasmosis). Measurement of circulating ICAM-1 serum levels was
      performed using a monoclonal antibody based ELISA, with healthy blood donors
      serving as the control group. Applying multiple variance analysis and the Student
      Newmann-Keuls test we found a statistically significant elevation of serum cICAM
      1 level in the HLA-B 27 neg. AU group (n:31), in the IU group (n:25) and in
      patients with sarcoidosis (n:18). Serum levels of HLA-B27 pos. AAU patients,
      patients with HCF and patients suffering from ocular toxoplasmosis did not differ
      significantly from levels of the control group.

PMID- 1358556
TI  - Distribution of IL-2R and CD45Ro expression on CD4+ and CD8+ T-lymphocytes in the
      peripheral blood of patients with posterior uveitis.
AB  - Different lines of evidence support a major role for activated T-lymphocytes in
      the pathogenesis of posterior uveitis. The initial site of activation of these
      autoreactive T-cells, either locally in the eye or in the peripheral immune
      compartment, is still unknown. This study was undertaken to investigate whether
      with currently available techniques, it is possible to detect alterations in the
      levels and subsets of activated T-cells in the peripheral blood of patients with
      posterior uveitis. For this reason, 3-colour immunofluorescent staining was
      performed to assess the distribution of IL-2 receptors (IL-2R) and the CD45RO
      antigen on CD4+ and CD8+ subsets of peripheral blood lymphocytes (PBLs) from
      patients with posterior uveitis (n = 29). Only the subgroup of patients with
      posterior uveitis as part of a systemic immune-mediated disease (sarcoidosis,
      Behcet's disease) (n = 9) showed a significant increase in IL-2R expression on
      peripheral blood lymphocytes (p less than 0.005) when compared to normals (n =
      12). This increased expression was reflected much more significantly in the CD4+
      (p less than 0.0005) rather than in the CD8+ subset (p less than 0.05) of
      lymphocytes. In contrast, no significant increase in CD45RO expression on either
      subset of T lymphocytes was found in any subgroup of posterior uveitis in
      comparison with normals.

PMID- 1358557
TI  - Experimental autoimmune uveoretinitis: a model system for immunointervention: a
      review.
AB  - Experimental autoimmune uveoretinitis (EAU) is a useful model of human posterior
      uveitis and as such, permits the analysis of strategies for immuno-intervention.
      Modulation of the autoimmune response may be attempted at the stages of induction
      of EAU, during homing of autoreactive lymphocytes to the target organ, the
      retina, or during the effector stage of the disease. This paper presents a brief
      overview of current immuno-therapeutic modalities and assesses the usefulness for
      extrapolation to human disease.

PMID- 1358558
TI  - Differential regulation of dopaminergic neurons in the mammalian brain: a brief
      review.
AB  - The mammalian brain contains anatomically distinct dopaminergic neuronal systems
      that subserve a variety of functions which include maintaining postural reflexes,
      modulating basic psychic processes, and controlling the secretion of hormones
      from the pituitary. In turn, these various dopaminergic neuronal systems are
      regulated by different mechanisms that are appropriate for the functions that
      they control. This is illustrated by comparing the responses to endocrinological
      and pharmacological manipulations of the nigrostriatal dopaminergic neuronal
      system that is involved with sensorimotor integration and the tuberoinfundibular
      dopaminergic neuronal system that tonically inhibits the release of prolactin.

PMID- 1358559
TI  - Symposium on Polyfunctional Cytokines: IL-6 and LIF. October 1-3, 1991.

PMID- 1358560
TI  - Functional anatomy of the neuroendocrine hypothalamus. Symposium. Budapest,
      Hungary, 8-10 October 1991.

PMID- 1358561
TI  - Intrahypothalamic neurohormonal interactions in the control of growth hormone
      secretion.
AB  - The secretion of growth hormone (GH, somatotropin) is regulated by two
      neurohormones: one inhibitory, somatotropin release-inhibiting hormone (SRIH) or
      somatostatin, and one stimulatory, GH-releasing hormone (GHRH). There are several
      lines of evidence for reciprocal interactions between SRIH and GHRH neuronal
      networks. Anatomically, GHRH terminals contact SRIH-containing neurons in the
      periventricular nucleus and SRIH-containing fibres innervate GHRH-containing
      neurons in the arcuate nucleus. Physiologically, SRIH and GHRH are secreted into
      the portal blood in complementary oscillating patterns. Results from
      immunizations with anti-SRIH antisera suggest that endogenous SRIH blocks GHRH
      release from the median eminence. Intracerebroventricular injections of SRIH
      stimulate secretion of GHRH indirectly, probably via autoinhibition of SRIH
      neurons in the anterior periventricular region. High resolution autoradiography
      allowed us to visualize high affinity, specific [125]SRIH receptors on 30% of
      GHRH mRNA-containing cells in the ventrolateral portion of the arcuate nucleus.
      The functional importance of these receptors was demonstrated by blocking
      endogenous SRIH action with cysteamine, which resulted in an increase in GHRH
      mRNA levels and desaturation of SRIH receptors in the ventrolateral part of the
      arcuate nucleus. Alterations in GH production caused by hypophysectomy or acute
      and chronic GH hypersecretion have opposite effects on the synthesis of SRIH and
      GHRH, giving further evidence for reciprocal interactions between these two
      neurohormonal systems.

PMID- 1358562
TI  - Erythromycin stimulates gallbladder emptying and motilin release by atropine
      sensitive pathways.
AB  - The effect of administering different doses of erythromycin on gallbladder
      emptying and plasma concentrations of immunoreactive motilin was investigated in
      healthy volunteers. Erythromycin was infused for 30 min at four different doses:
      20, 50, 100, and 1000 mg/hr. Gallbladder volume was determined by ultrasound
      scanning every 10 min for 60 min. All doses, except 20 mg/hr, provoked a
      significant reduction in gallbladder volume (P < 0.01). The gallbladder emptying
      peak occurred after 20 min infusion. It was approximately 40-45% of basal volume
      and 60-70% of the emptying observed after a standard meal. At 100 mg/hr,
      erythromycin caused a 2.5-fold increase in plasma motilin concentration, which
      reached a peak after 30 min infusion. Plasma motilin peaked following maximum
      gallbladder emptying in all subjects. To evaluate whether cholinergic pathways
      were implicated in the action of erythromycin, 100 mg/hr erythromycin was infused
      together with 6 micrograms/kg/hr atropine. Atropine inhibited both gallbladder
      emptying and motilin release (P < 0.001). Infusion of 1 microgram/kg/hr
      somatostatin had the same inhibitory effects (P < 0.001). Our results suggest
      that atropine acts by inhibiting an erythromycin-activated cholinergic neural
      mechanism. Somatostatin could exert its inhibitory effect by blocking the release
      of acetylcholine from neural terminations.

PMID- 1358563
TI  - Controlled study of oxatomide vs disodium chromoglycate for treating adverse
      reactions to food.
AB  - A controlled, cross-over trial was carried out to compare the efficacy and safety
      of oxatomide vs disodium chromoglycate (DSCG) for treating food allergy and
      intolerance. Twenty patients (15F, 5M; mean age 36.6 years), with chronic
      urticaria (twelve patients) or eczema (eight patients) caused by food allergy
      (ten cases) or food intolerance (ten cases), were treated with oxatomide (60
      mg/day in a single evening administration) and with DSCG (2000 mg/day) for six
      weeks. The two treatments were separated by a 3-week wash-out period. All the
      patients completed the trial. During the treatment, both drugs succeeded in
      controlling the symptoms. With oxatomide, the wheals totally disappeared from 75%
      of the patients (p = 0.00135), the eczematous lesions disappeared from 64% (p =
      0.056), and the itching from 70% (p = 0.00012); the figures for DSCG were 33%,
      50% (p = 0.038) and 50%, respectively. Both drugs were well tolerated and there
      was no need to discontinue the treatment of any of the patients.

PMID- 1358564
TI  - Induction of CYP1A1 mRNA in rat epidermis and cultured human epidermal
      keratinocytes by benz(a)anthracene and beta-naphthoflavone.
AB  - Cytochrome P-4501A1 (CYP1A1) plays a major role in the bioactivation of
      procarcinogens in target tissues, including skin. However, the factors
      controlling CYP1A1 expression in mammalian skin are unknown. Utilizing the
      reverse transcriptase-linked polymerase chain reaction, we analyzed the effect of
      treatment with beta-naphthoflavone (beta-NF) and benz(a)anthracene on the
      expression of CYP1A1 mRNA in rat epidermis and normal human epidermal
      keratinocytes (NHEK). Inducer treatment of rats and NHEKs resulted in several
      fold increases in aryl hydrocarbon hydroxylase activity. Following inducer
      treatment of adult or neonatal rats, increase in CYP1A1 gene message occurred as
      compared with that in controls. Higher basal level and inducibility were detected
      in mature rather than in 4-day-old rats. This induction occurred as early as 4 hr
      after beta-NF application. Exposure to beta-NF and benz(a)anthracene also
      resulted in substantial increases in gene message in NHEK. Northern blot analyses
      complemented the polymerase chain reaction data. These results indicate that
      CYP1A1 gene expression is increased in mammalian epidermis by inducers of
      epidermal aryl hydrocarbon hydroxylase activity.

PMID- 1358565
TI  - Conjugation of dinitrofluorobenzene to plasma proteins in vivo in the rat.
AB  - The extent of protein dinitrophenylation was determined in plasma and other
      tissues of anesthetized rats after administration of the model immunogen
      [3H]dinitrofluorobenzene (DNFB) (25 mg/kg; 5-25 microCi). DNFB was given by the
      intravenous, intraportal, intramuscular, or oral route. Irreversible binding was
      determined radiometrically after exhaustive solvent extraction of plasma or organ
      proteins. The extent of binding was high in plasma after parenteral
      administration (approximately 1% dose/ml plasma), but less (approximately 0.1%
      dose/ml) if DNFB was given orally. Low levels of radioactivity were bound
      irreversibly in liver (0.01-0.13% dose/g) and kidney (0.03-0.10% dose/g) and only
      residual amounts in other organs. Western blotting was used to identify target
      proteins in plasma, liver, and kidney using a specific antidinitrophenyl
      antiserum. No dinitrophenylation could be detected in liver or kidney samples,
      but strong recognition of two protein bands was observed in plasma. Bands with
      the same apparent molecular masses (67 and 44 kDa) were seen when DNFB was
      incubated with rat plasma in vitro. Preliminary evidence for these proteins being
      albumin and alpha 1-acid glycoprotein, respectively, is presented. The latter may
      be important for interindividual variability in immune responsiveness, because it
      is an acute phase protein whose levels fluctuate widely during disease states.

PMID- 1358566
TI  - Isolation, purification, and characterization of two new chemical decomposition
      products of methylazoxyprocarbazine.
AB  - We have previously reported that the antineoplastic agent, procarbazine, in
      aqueous solutions was chemically oxidized to its azoxy metabolites (methylazoxy
      and benzylazoxy). To determine if there was additional metabolism of the most
      active metabolite, methylazoxyprocarbazine, it was incubated in the presence and
      absence of CCRF-CEM human leukemia cells. Incubations were extracted, and
      potential metabolites were detected by HPLC with UV detection and by combined
      HPLC and thermospray mass spectrometric analysis. The major metabolite identified
      by HPLC with UV detection of the extracts was N-isopropyl-p-formylbenzamide; this
      was identified by comparison of its retention time with that of a synthesized
      standard. This identification was further corroborated by HPLC/thermospray mass
      spectrometry (LC/MS). Analysis of the extracts by LC/MS also showed the presence
      of a closely eluting peak that had a protonated molecular ion at m/z 207. This
      new metabolite was identified as N-isopropyl-(benzene-1,4-bis-carboxamide) by 1H
      NMR and gas chromatography/ion trap mass spectrometry. This metabolite is
      postulated to arise from breakage of the N-N bond in the hydrazine portion of the
      molecule. Reconstructed ion (m/z 236) current profiles from the analysis of the
      cell extracts indicated that there was only a trace amount of
      methylazoxyprocarbazine left after a 72-hr incubation. Interestingly, a peak with
      the same molecular weight as the parent compound (methylazoxyprocarbazine) was
      observed in the cellular incubations and also in extracts of control incubations
      in which methylazoxyprocarbazine was incubated in medium without cells. This
      unknown was silylated and identified as a hydroxyazo compound by an ion trap mass
      spectrometer operated under both single and multiple-stage mass analysis.
      Formation of this decomposition product appears to involve a novel intramolecular
      rearrangement of methylazoxyprocarbazine in solution. This pathway may be
      responsible for the formation of the ultimate cytotoxic species by chemical
      decomposition of procarbazine.

PMID- 1358567
TI  - Effects of dose, strain, and dosing vehicle on methacrylonitrile disposition in
      rats and identification of a novel-exhaled metabolite.
AB  - Methacrylonitrile (MAN), an aliphatic nitrile used in the production of plastics
      and elastomers, is structurally related to the known animal carcinogen,
      acrylonitrile. Although MAN has potential to cause significant toxicity, minimal
      information is available on its toxicity or fate. Current studies were designed
      to investigate the biological fate of [2-14C]MAN in male F344 rats. Following
      gavage administration of 115, 11.5, or 1.15 mg MAN/kg in water, male F344 rats
      were placed in glass metabolism cages and urine, expired air, and feces were
      collected. Rats were sacrificed at various times, and the concentration of MAN
      derived radioactivity in tissues was determined. MAN was rapidly absorbed from
      the gastrointestinal tract and distributed to all major tissues. After gavage
      administration of 1.15-115 mg/kg, [2-14C]MAN is primarily eliminated in the
      expired air. Sixty to 70% of the low and medium doses were exhaled as 14CO2 in 72
      hr compared with 25% of the highest dose. Whereas 40% of the high dose was
      expired as organic volatiles in 72 hr, only 9-12% of the low and medium doses
      were exhaled as such. It is therefore apparent that saturation of MAN metabolism
      occurs at the high dose. HPLC analysis of expired organic volatiles from MAN
      treated rats showed that it contained two components that were identified as
      unchanged MAN and acetone. The MAN:acetone ratio was directly proportional to
      dose and decreased as a function of time. Urinary excretion accounted for 20-30%
      of all MAN doses within 72 hr after dosing. Investigating the effect of dosing
      vehicle on MAN disposition in rats revealed that administration of 115 mg MAN/kg
      in oil resulted in the death of rats within 24 hr after treatment. Furthermore,
      monitoring the fate of MAN in these rats before death showed that a significantly
      higher percentage of the dose was eliminated in urine and expired air. Analysis
      of this expired air also revealed that significantly more acetone and less
      unchanged MAN were exhaled by these animals. It is apparent that administration
      of MAN to F344 rats in oil resulted in slower absorption, decreased elimination
      of unchanged MAN, and increased metabolism to acetone and/or decreased
      degradation of acetone to CO2. The combination of these effects of an oil vehicle
      may have contributed to the death of rats by MAN. Comparison of the metabolism
      and disposition of MAN in F344 and Sprague-Dawley rats showed minor differences
      between the two strains.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1358568
TI  - Pharmacokinetics and renal handling of enprofylline in pregnant rats.
AB  - The pharmacokinetics and renal handling of enprofylline during pregnancy were
      investigated in Sprague-Dawley rats. Significant differences in the
      pharmacokinetic parameters of enprofylline were observed between nonpregnant rats
      and pregnant rats on the 20th day of gestation: volume of distribution was
      higher, and systemic clearance was lower in pregnant rats. Parameters obtained
      from rats at 7 days postpartum were the same as those obtained from nonpregnant
      rats. There were no significant differences in the fraction of urinary excretion
      of enprofylline between nonpregnant and pregnant rats. The protein binding of
      enprofylline in the plasma of pregnant rats was significantly lower than in
      nonpregnant rats, as a decrease in the albumin concentration consequentially
      reduced the binding capacity of enprofylline. The volume of distribution for
      unbound enprofylline in pregnant rats was not significantly different from
      nonpregnant rats, although a significant decrease was observed in pregnant rats
      in the systemic clearance for unbound enprofylline. In addition, the clearance
      ratio was lower in pregnant rats (2.8) when compared with nonpregnant rats (6.4).
      Pregnancy caused a decrease in the apparent maximum capacity of transport (Vmax)
      from 29.9 to 20.8 micrograms/min and in the Michaelis-Menten constant (KM) from
      2.59 to 2.26 micrograms/ml, indicating that the tubular secretion ability of
      enprofylline becomes reduced during pregnancy. These results suggest that changes
      that occur in the plasma protein binding behavior and in renal handling as a
      result of pregnancy are primary factors influencing the disposition of
      enprofylline during pregnancy.

PMID- 1358569
TI  - Species and tissue differences in the microsomal oxidation of 1,3-butadiene and
      the glutathione conjugation of butadiene monoxide in mice and rats. Possible role
      in 1,3-butadiene-induced toxicity.
AB  - Rat and mouse liver, lung, and kidney microsomes metabolized 1,3-butadiene to
      butadiene monoxide (BM), whereas microsomes from testis, one of the target organs
      of 1,3-butadiene toxicity in both species, were ineffective. 1,3-Butadiene
      metabolism was NADPH-dependent and inhibited by 1-benzylimidazole. With mouse
      microsomes, a 4-fold higher rate was measured with kidney compared with liver or
      lung, which exhibited similar rates. With rat microsomes, the rate obtained with
      liver was 2- and 6-fold higher than those of lung and kidney, respectively.
      Overall, oxidation rates by mouse tissues were higher than those of rat tissues.
      These results, along with the finding that BM was stable in the presence of rat
      plasma, provide evidence for the role of circulating metabolites in 1,3-butadiene
      induced toxicity. Furthermore, crotonaldehyde, a known carcinogen, was detected
      with mouse tissues only. Thus, in addition to the greater ability of mouse
      tissues to produce BM, formation of crotonaldehye may contribute to the greater
      susceptibility of mice to 1,3-butadiene toxicity compared with rats. Nearly all
      rat liver glutathione S-transferase activity was localized to the cytosol
      (greater than 96%). BM glutathione conjugation rates with liver cytosol of both
      species were similar, whereas conjugation rates with mouse lung and kidney
      cytosol were 4- and 2-fold higher than those of rat lung and kidney,
      respectively. Thus, species differences in BM glutathione conjugation do not
      correlate with species susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358570
TI  - Identification and comparison of the urinary metabolites of [1,2,3-13C3]acrylic
      acid and [1,2,3-13C3]propionic acid in the rat by homonuclear 13C nuclear
      magnetic resonance spectroscopy.
AB  - Acrylic acid (AA) and its esters are used extensively for the production of a
      variety of polymers. Despite their ubiquitous nature, little has been reported on
      the metabolism of the parent acid. The metabolites of AA may be volatile,
      unstable, polar, and thus difficult to isolate. Therefore, 13C NMR was used to
      help identify and compare directly the urinary metabolites of both 99% 13C
      enriched AA and propionic acid (PA). Male Sprague-Dawley rats received [1,2,3
      13C]AA (400 mg/kg in water p.o.) or an equimolar dose of [1,2,3-13C]propionate
      together with a radioactive tracer, [2,3-14C]AA, or [1-14C]propionate,
      respectively, and excreta were collected for 72 hr. For both acids, expiration of
      14CO2 was the major route of elimination of radiolabel (approximately 80%).
      Approximately 6% of the dose was excreted in the urine. Urine was analyzed
      directly using proton-decoupled 13C and two-dimensional 13C homonuclear
      correlated NMR spectroscopy. The urine from AA-treated rats revealed major
      signals, the intensity of which was time-dependent, from at least five 13C
      enriched metabolites of AA. Signals have been assigned to 3-hydroxypropionic
      acid, N-acetyl-S-(2-carboxyethyl)cysteine, and N-acetyl-S-(2
      carboxyethyl)cysteine-S-oxide by comparison with spectra of authentic standards.
      No unchanged AA was detected. In contrast, the spectra of urine from a propionate
      treated rat revealed only a few minor 13C-enriched signals that were assigned to
      methylmalonic acid. No unchanged PA was detected.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1358571
TI  - Pharmacokinetics of intravenously injected [3H]tetrachloro(D,L-trans)1,2
      diaminocyclohexane platinum (IV) (tetraplatin) in mice.
AB  - Platinum (Pt) complexes with diaminocyclohexane (DACH) carrier ligand are of
      interest because of their effectiveness against tumor cells resistant to
      cisplatin. We examined the pharmacokinetics and in vivo stability of Pt-N bond of
      tetraplatin using radiolabeled drug containing the 1,2-[4,5-3H]diaminocyclohexane
      ([3H]DACH) moiety and monitored the ratio 3H:Pt in biological samples. Following
      intravenous administration of [3H]tetraplatin (5 mg/kg and 163 microCi/kg) in
      mice, blood, urine, and tissue samples were collected and analyzed for both Pt
      level and radioactivity using flameless atomic absorption spectrophotometry and
      scintillation counting, respectively. In plasma, half-lives of 5 min (alpha
      phase) and 1 hr (beta-phase) were generated for both "free" 3H and Pt. The 3H:Pt
      ratio of "free" levels did not change for at least 2 hr after intravenous
      administration. This indicated that the Pt-N bond was largely intact in the free
      drug fraction over this time period. In blood and plasma, however, there were
      decreases in "total" 3H:Pt ratios by 21 and 13% over 2 hr and 38 and 51% over 4
      days, respectively, as a result of a greater rate of elimination of 3H than Pt.
      Urinary excretion in mice of 3H and Pt accounted for 55 and 43% of the
      administered dose, respectively, in 4 days, with 35 and 30% being excreted in the
      first 7 hr. The 3H:Pt ratio in urine increased 1.4-fold between 7 and 72 hr, and
      this was a further indication of dissociation of DACH ligand from Pt. Tissue
      distribution study revealed that the DACH moiety was also being removed more
      rapidly, and this was particularly evident in the liver and spleen than in other
      tissues.

PMID- 1358572
TI  - Disposition of acrivastine in the male beagle dog.
AB  - Three male beagle dogs were given 10 mg/kg iv and oral doses of [14C]acrivastine,
      a novel nonsedating antihistaminic agent, in a nonrandomized crossover
      experiment. Urine and feces were collected for 72 hr after dosing. After iv
      dosing, a mean of 34% was recovered in the urine, and 63% was recovered in the
      feces. After po dosing, a mean of 29% of the radiocarbon was recovered in the
      urine, and 63% was recovered in the feces (dose adjusted for 14% lost in
      vomitus). Acrivastine and three major metabolites were detected in the excreta.
      The metabolites were identified as a side-chain-reduced analog of acrivastine
      (metabolite 3, 270C81), a gamma-aminobutyric acid analog of 270C81 (metabolite
      2), and a benzoic acid analog of 270C81 (metabolite 1). After iv dosing, 34% of
      the dose was excreted as parent drug, 21% as metabolite 3, 15% as metabolite 2,
      and 6% as metabolite 1, while after po dosing, 35% of the dose was excreted as
      parent drug, 18% as metabolite 3, 11% as metabolite 2, and 7% as metabolite 1.
      Pharmacokinetic analysis of acrivastine plasma concentration-time curves after
      both routes of administration indicated a mean total body clearance of 17.3
      ml/min/kg, a Vss of 0.93 liter/kg, a terminal half-life of 0.7 hr, and an oral
      bioavailability of 40%. The apparent plasma half-life of the metabolite, 270C81,
      was 1.5 hr. Analysis of AUC values indicated that greater amounts of 270C81 than
      acrivastine circulated in plasma after both iv and po dosing, and that first-pass
      metabolism of acrivastine to 270C81 occurred. The results indicated that
      acrivastine was extensively metabolized in the dog to 270C81 and suggested that
      270C81 itself underwent further metabolism to metabolites 1 and 2.

PMID- 1358573
TI  - Bromo(monohydroxy)phenyl mercapturic acids. A new class of mercapturic acids from
      bromobenzene-treated rats.
AB  - Alkaline permethylation and GC/MS analysis of urinary mercapturic acids from rats
      given bromobenzene yielded several quinone-derived bromodimethoxythioanisole
      isomers as expected. Unexpectedly, seven bromomonomethoxythioanisole isomers were
      also observed, suggesting the presence of bromomonohydroxyphenyl mercapturic
      acids in the urine. Alkaline permethylation of synthetic 4- and 5-bromo-2
      hydroxyphenyl mercapturic acid gave 4- and 5-bromo-2-methoxythioanisole,
      respectively, which were also observed after alkaline permethylation of urine
      from bromobenzene-treated rats, as was 2-bromo-4-methoxythioanisole. To explore
      the biosynthetic origin of the bromonohydroxyphenyl mercapturic acids, rats were
      separately dosed intraperitoneally with synthetic racemic 2-, 3-, or 4
      bromophenyl mercapturic acid, or biosynthetic L-(-)-4-bromophenyl mercapturic
      acid, or a biosynthetic mixture of the 3,4- and 4,3-premercapturic acids from
      bromobenzene, and their urine (0-24 hr) analyzed by alkaline permethylation and
      GC/MS. The administered mercapturic acids and premercapturic acids were partly
      excreted unchanged (60-80% and 24%, respectively), but both gave rise to
      bromomonohydroxyphenyl mercapturic acids (0.1-5.2% of dose). Results indicated
      that the latter could be formed by 1) dehydrogenation of premercapturic acids and
      2) hydroxylation of mercapturic acids (or their cysteine equivalents).

PMID- 1358574
TI  - Disposition of metabolically labeled recombinant soluble CD4 (sT4) in male
      Sprague-Dawley rats following intravenous and subcutaneous administration.
AB  - Soluble CD4 (sT4) has been metabolically labeled with [3H]leucine in Chinese
      hamster ovary cells and purified by S Sepharose chromatography. Over 250 microCi
      of high specific radioactivity [3H]sT4 (42 Ci/mmol) was prepared. The
      radiolabeled molecule was chemically and biologically representative of the
      unlabeled molecule and thus appropriate for in vivo metabolic investigations. To
      explore the biotransformation and disposition of a recombinant protein, this
      uniformly labeled [3H]sT4 was administered intravenously and subcutaneously to
      male Sprague-Dawley rats. Following a single dose of 0.3 mg/kg, blood samples
      were collected for 9 days and analyzed for total radioactivity, total plasma
      radioactivity, trichloroacetic acid-precipitable plasma radioactivity, sT4
      related plasma radioactivity (by extraction with a Sepharose-bound polyclonal
      anti-sT4 antibody), and plasma sT4 concentration (by an N and C terminal-specific
      Leu3A/OKT4 ELISA). Excreta were analyzed for total radioactivity. The
      pharmacokinetic profiles of intact sT4 were as expected from the results of
      previous studies. sT4 was cleared rapidly from plasma with an elimination t1/2 of
      7 min (intravenous), and low sT4 levels were observed following subcutaneous
      administration. Comparison of the kinetic profiles of total radiolabel,
      trichloroacetic acid-precipitable radiolabel, sT4-related radiolabel, and the
      isolation of plasma proteins containing tritium have led to the following
      conclusions. One of the major metabolic pathways for [3H]sT4 was the degradation
      of the polypeptide to its constituent amino acids, which were subsequently
      incorporated into endogenous proteins. Incorporation of tritium into blood cell
      proteins resulted in a prolonged radiolabel blood profile (t1/2 greater than 250
      hr). Following subcutaneous administration, [3H] sT4 was significantly degraded
      before reaching the vascular circulation.

PMID- 1358575
TI  - Pharmacokinetics and pharmacodynamics of topotecan in patients with advanced
      cancer.
AB  - Topotecan, a semisynthetic water-soluble analog of camptothecin, is the first
      topoisomerase I-directed drug to enter clinical trial in the United States in
      over 20 yr. In this study, 30-min infusions of topotecan were administered daily
      for 5 days every 3 weeks at doses ranging from 0.5 to 2.5 mg/m2. Topotecan is
      reversibly hydrolyzed in a pH-dependent reaction in aqueous solutions to the ring
      open hydroxy acid. The disposition of the closed ring lactone has been studied in
      26 patients, and the disposition of both lactone and hydroxy acid has been
      studied in 12 patients. The clearance rate for topotecan lactone was 1220
      ml/min/m2, with a range of 300-4760 ml/min/m2. The clearance rate for total
      topotecan (lactone and hydroxy acid) was 493 ml/min/m2, with a range of 163-815
      ml/min/m2. A model for the disposition of lactone and hydroxy acid incorporating
      both reversible hydrolysis and elimination was developed. We have shown that
      topotecan is partially hydrolyzed prior to administration in parenteral
      solutions, and that clearance of the parent compound proceeds in vivo by
      conversion to hydroxy acid and elimination. Renal clearance accounted for 30 +/-
      18% of drug elimination in patients. The relationship between topotecan dose and
      myelotoxicity is well fit by a sigmoidal Emax model, as is the relationship
      between total topotecan area under the concentration-time curve and
      myelotoxicity. The disposition of topotecan was also studied in mice. The
      clearance rate for total topotecan in mice was 330 ml/min/m2 after administration
      of topotecan lactone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358576
TI  - Exogenous glutathione decreases cellular cadmium uptake and toxicity.
AB  - The effect of intracellular glutathione (GSH) on cadmium metabolism and toxicity
      has been extensively investigated. However, little is known regarding the effect
      of extracellular GSH on cellular cadmium responses. Therefore, this study was
      conducted to investigate the effect of exogenously added GSH on cadmium toxicity
      in normal rat kidney fibroblasts (NRK-49F). Exponentially growing NRK-49F cells
      were arrested by serum deprivation and then stimulated with epidermal growth
      factor (EGF). CdCl2, at concentrations that range from 0.25 to 2 microM, was
      found to inhibit, in a dose-dependent fashion, the EGF-induced DNA synthesis (as
      judged by [3H]thymidine incorporation) in the cells. A long-term survival assay
      revealed that CdCl2 above 1 microM was toxic to the cells. Exogenous GSH had a
      dose-dependent antagonistic effect on cadmium inhibition of EGF-induced DNA
      synthesis, and 1 mM GSH was found to block completely cadmium inhibition of both
      EGF-induced DNA synthesis and cell survival. Exogenously added GSH did not
      increase intracellular GSH levels but decreased cadmium accumulation by the
      cells. This decrease was primarily caused by a reduced cadmium uptake. Further
      studies indicated that exogenous GSH would form a complex with cadmium outside of
      the cells preventing cellular cadmium uptake. This may explain the mechanism of
      action of the exogenous GSH in cytoprotection against cadmium. The results also
      suggested a practical potential for GSH as a cadmium chelator. If GSH were
      coadministered with a cadmium mobilizer and a gamma-glutamyl transpeptidase
      inhibitor, it could enhance cadmium excretion from the body.

PMID- 1358577
TI  - Enantioselectivity of microsomal and cytosolic esterases in rat intestinal
      mucosa.
AB  - Enantioselectivity of esterases, contained in 9,000g supernatant fraction (S9)
      prepared from homogenate of small intestinal mucosa of male Sprague-Dawley rats
      and the subsequent 105,000g supernatant (cytosol) and pellet (microsomes)
      prepared from S9, was studied using racemic oxazepam 3-acetate (rac-OXA) as the
      substrate. Esterases in S9 were enantioselective in hydrolyzing either S-OXA or R
      OXA, depending on a particular subcellular preparation. Cytosolic and microsomal
      esterases had opposite enantioselectivity and selectively hydrolyzed S-OXA and R
      OXA, respectively. Enantioselectivity of esterases solubilized from microsomes
      with Triton X-100 (0.1%, w/v) was identical to that of the membrane-bound
      microsomal esterases. Cytosolic esterases were more sensitive to temperature than
      either solubilized or membrane-bound microsomal esterases. In the presence of
      paraoxon (1 microM), the esterases selective toward R-OXA in both microsomes and
      S9 were completely inhibited, whereas the esterases selective toward S-OXA in
      cytosol were inhibited by approximately 6%. These results indicate that cytosolic
      and microsomal esterases in rat small intestinal mucosa are distinctly different
      enzymes, with opposite enantioselectivity in the hydrolysis of rac-OXA.

PMID- 1358578
TI  - Concomitant induction of microsomal epoxide hydrolase and UDP
      glucuronosyltransferase activities by dipyridine compounds.
AB  - The coordinated response of the major rat hepatic phase II xenobiotic
      metabolizing enzymes following 3-day exposure to diaryl compounds was
      investigated. Four diaryl compounds containing heterocyclic nitrogen atoms
      elevated microsomal epoxide hydrolase activity from 2- to 4-fold. Equivalent
      compounds lacking the heteroatom, when given in the same dosing regimen (75
      mg/kg, ig, daily for 3 days), did not induce this or any other drug-metabolizing
      enzyme activity. Epoxide hydrolase activity closely paralleled UDP
      glucuronosyltransferase activity toward three aglycones: 4-nitrophenol (r =
      0.87), morphine (r = 0.84), and 1-naphthol (r = 0.78). There was less correlation
      (r = 0.60) between epoxide hydrolase activity and both UDP
      glucuronosyltransferase activity toward testosterone and cytosolic glutathione S
      transferase activity. There was no correlation between microsomal epoxide
      hydrolase activity and cytochrome P-450 or the monooxygenase reaction (4
      nitrophenol hydroxylase) preferentially induced by pyridine-containing compounds.
      Induction of rat hepatic microsomal epoxide hydrolase activity by some pyridine
      containing compounds appears coordinately regulated with glucuronidation rather
      than oxidation enzymes.

PMID- 1358579
TI  - Comparative pharmacokinetics of cefoperazone and cephradine in untreated
      streptozotocin diabetic rats.
AB  - Experimental diabetes mellitus was induced in adult male rats by injecting
      streptozotocin (STZ; 60 mg/kg iv) for the purpose of surveying changes in the
      pharmacokinetics of biliary excretion after the intravenous administration of 40
      mg/kg of cefoperazone (CPZ) or cephradine (CED). CPZ, CED, and other organic
      anions share affinity for the organic anion transport system in the bile
      canalicular membrane. The STZ treatment had a marked influence on the
      distribution and elimination of both cephalosporins. The blood levels of both
      cephalosporins at each time point after administration differed significantly
      between the STZ-treated and control rats. The values of mean residence time (MRT)
      of CPZ and CED were significantly decreased in the STZ-treated rats. Basal bile
      flow rates were increased after the administration of CPZ in the control and STZ
      treated rats. Biliary clearance (CLbile) of CPZ was more than 60% of the CLtot,
      whereas CLbile of CED was less than 20% of CLtot in both groups of rats. The mean
      CLbile value of CPZ in the STZ-treated rats was 1.0 ml/min higher than that of
      the control rats, whereas the mean CLbile value of CED was almost the same as
      that of the control rats. The increased CLbile of CPZ suggested that diabetes
      alters the biliary excretion of CPZ. The changes in MRT of CPZ in the STZ-treated
      and control rats are mainly caused by an increase in the biliary excretory rate
      and renal clearance. The changes in MRT of CED in the STZ-treated and control
      rats are caused by a decrease in the apparent volume of distribution and
      increased renal clearance.

PMID- 1358580
TI  - The pharmacokinetics of 1,2-diethyl-3-hydroxypyridin-4-one (CP94) in rats.
AB  - The pharmacokinetics of 1,2-diethyl-3-hydroxypyridin-4-one (CP94) and its 2-(1
      hydroxyethyl) metabolite (metabolite A) were examined in male Wistar rats using a
      chronically cannulated conscious-rat model. Serial blood samples were assayed by
      a reversed phase HPLC method with UV detection. Following iv doses of 25, 50, and
      100 mg/kg, the parent compound was eliminated from blood in a biexponential
      fashion with an average systemic clearance of 1.5 liters/hr/kg. The mean terminal
      elimination half-life was 2.02 hr and the mean volume of distribution at steady
      state was 2.69 liters/kg. The areas under the curve (AUCs) for the 25, 50, and
      100 mg/kg iv doses were 15, 36, and 72 micrograms/ml/hr, respectively, suggesting
      that the disposition of CP94 in rats obeys linear kinetics. The oral
      bioavailability of CP94 (100 mg/kg) was about 53%. Peak blood concentration
      occurred at about 0.5 hr after oral administration. Following iv doses of CP94 at
      25, 50, and 100 mg/kg, metabolite A peaked at about 0.75 hr.

PMID- 1358581
TI  - Metabolism of 7-(1,3-thiazolidin-2-ylmethyl)theophylline by rat liver microsomes.
      Evidence for a monooxygenase-dependent step in 1,3-thiazolidine ring cleavage.
AB  - Metabolic transformation of the mucoregulator and bronchodilator 7-(1,3
      thiazolidin-2-ylmethyl)theophylline was studied in vitro with a rat liver
      microsomal preparation containing a NADPH-generating system. The only metabolite
      observed was 7-theophyllinacetaldehyde. In contrast to previous literature
      pointing out the chemical nature of 2-substituted thiazolidine ring cleavage, the
      formation of 7-theophyllinacetaldehyde was mediated by monooxygenase-dependent
      oxidation. Possibly an unstable sulfoxide was the first metabolic product,
      rapidly converted to 7-theophyllinacetaldehyde by hydrolysis. The sulfoxidation
      was apparently catalyzed mainly by flavin-containing monooxygenases, as selective
      thermal inactivation and methymazole significantly reduced the rate of formation
      of the metabolite. No N7-dealkylation pathway producing theophylline was
      detected, indicating a high regioselectivity in in vitro metabolism, due to the
      nucleophilicity of the sulfur atom.

PMID- 1358582
TI  - Pharmacokinetics in mice of the anti-retrovirus agent 9-(2
      phosphonylmethoxyethyl)adenine.
AB  - The pharmacokinetics of 9-(2-phosphonylmethoxyethyl)adenine (PMEA), a potent
      inhibitor of retrovirus (i.e. human immunodeficiency virus) replication was
      determined in mice. Upon iv bolus administration of PMEA at 25, 100, or 500
      mg/kg, PMEA was rapidly cleared from the plasma in a monoexponential and dose
      independent manner (half-life, 7-12.5 min; distribution volume, 0.30-0.36
      liter/kg; total body clearance, 1.21-2.41 liters/hr/kg). Irrespective of the
      initial PMEA dose, 67% of unchanged PMEA was recovered from the urine of mice
      within 24 hr after administration of PMEA. [3H]PMEA, administered as an iv bolus
      injection, mainly accumulated in the kidney, liver, and lungs. Significant
      amounts of monophosphorylated PMEA were detected in kidney and liver, but not
      other tissues, at 10, 30, and 60 min after iv administration of PMEA. Low but
      significant levels of PMEA were attained in the brain.

PMID- 1358583
TI  - Isolation and structural characterization by spectroscopic methods of two
      glucuronide metabolites of mexiletine after N-oxidation and deamination.
AB  - Urine samples from control and mexiletine-treated human subjects or rabbits (test
      group) were collected and passed through an ion exchange resin to isolate polar
      compounds. Methanolic eluates from control and test urines were analyzed by TLC.
      Exposure to p-dimethylaminocinnamaldehyde gave an additional intense pink band at
      Rt 0.40-0.45 in TLC analysis of test urine eluate when compared to control urine
      eluate. Non-exposed silica at this Rt was scraped and metabolites were extracted
      with methanol. Hydrolysis of this methanolic extract at 100 degrees C with
      hydrochloric acid released mexiletine. GC/MS and fast atom bombardment mass
      spectrometry analyses of nonhydrolyzed methanolic extracts evidenced the presence
      of two conjugated metabolites of mexiletine, namely, N-hydroxymexiletine
      glucuronide and mexiletine alcohol glucuronide. Synthetic compounds corresponding
      to these metabolites were obtained and spectra compared with those of isolated
      metabolites from urine. Definite structure assignment of N-hydroxymexiletine
      glucuronide was obtained from NMR spectrometry which confirmed the structure to
      be a hydoxylamine glucuronide (N-O-C link) and showed that the glycoside moiety
      was in the beta configuration. Thus, it is proposed that N-hydroxymexiletine
      glucuronide corresponds to mexiletine acid-labile conjugate and represents a
      major metabolic pathway in the disposition of mexiletine.

PMID- 1358584
TI  - Cytochrome P-450-mediated N-dechloroethylation of cyclophosphamide and ifosfamide
      in the rat.

PMID- 1358585
TI  - Trimethadione metabolism as an index of hepatic drug-oxidizing capacity in dogs
      with liver ischemia.

PMID- 1358586
TI  - Inhibition of rabbit microsomal cytochrome P-450 2E1-dependent p-nitrophenol
      hydroxylation by substituted benzene derivatives.

PMID- 1358587
TI  - Benzodiazepine use and HIV risk-taking behaviour among injecting drug users.
AB  - This paper examines the prevalence of benzodiazepine use, and its relationship to
      other drug use and HIV risk-taking among a sample of 1245 injecting drug users
      (IDU). Approximately a third (36.6%) of the sample had used benzodiazepines
      during their last typical month of injecting. Benzodiazepine users had injected
      more frequently, injected more heroin and amphetamines, and had more poly-drug
      use than other IDU. They also had higher levels of HIV risk-taking, having shared
      injecting equipment more frequently and with more people. There were no
      differences between groups in number of sexual partners or condom use, although
      benzodiazepine users were more likely to have been paid for sex. The demographic
      and drug use variables indicate that benzodiazepine users are a more
      dysfunctional subgroup of IDU who require particular attention in HIV
      interventions.

PMID- 1358588
TI  - A hospital-based benzodiazepine policy.

PMID- 1358589
TI  - [Type-2B multiple endocrine neoplasms with diffuse liver metastases as the cause
      of chronic diarrhea].
AB  - During examination before surgical correction of pes valgus a 20-year-old man
      reported having 3-5 pasty, foul smelling diarrhoeic motions per day for the past
      3 years. He was noted to have rather thick lips and Marfan-like body build.
      Erythrocyte sedimentation rate was 18/34 mm, serum activity of GOT 22.5 U/l, GPT
      35.7 U/l. Faecal weight was increased to 640 g/d, fat content to 12 g/d. Serum
      levels of the carcinoembryonic antigen (2494 ng/ml; normal: < 2.5) and of
      calcitonin (1,619,760 pg/ml; normal < 100) were elevated. Gastroscopy, partial
      coloscopy, colon-contrast imaging, ultrasonography and computed tomography of the
      neck and abdomen, as well as magnetic nuclear imaging of the neck were all
      normal. But laparoscopy revealed the liver to be infiltrated by small whitish
      nodules which immunohistologically proved to be metastases of a C-cell carcinoma.
      Total thyroidectomy was performed and the diagnosis of a C-cell carcinoma of the
      thyroid confirmed intra-operatively. After the operation the diarrhoea was
      stopped with codeine (9 mg/d). In case of tumour progression, therapy with
      octreotide, a somatostatin analogue, will be carried out. The concomitant
      occurrence of C-cell carcinoma, Marfan-like body build, thick lips and skeletal
      changes is typical of multiple endocrine neoplasia type 2B, which is caused by a
      chromosomal defect.

PMID- 1358591
TI  - Expression patterns of the homeobox gene, Hox-8, in the mouse embryo suggest a
      role in specifying tooth initiation and shape.
AB  - We have studied the expression patterns of the newly isolated homeobox gene, Hox
      8 by in situ hybridisation to sections of the developing heads of mouse embryos
      between E9 and E17.5, and compared them to Hox-7 expression patterns in adjacent
      sections. This paper concentrates on the interesting expression patterns of Hox-8
      during initiation and development of the molar and incisor teeth. Hox-8
      expression domains are present in the neural crest-derived mesenchyme beneath
      sites of future tooth formation, in a proximo-distal gradient. Tooth development
      is initiated in the oral epithelium which subsequently thickens in discrete sites
      and invaginates to form the dental lamina. Hox-8 expression in mouse oral
      epithelium is first evident at the sites of the dental placodes, suggesting a
      role in the specification of tooth position. Subsequently, in molar teeth, this
      patch of Hox-8 expressing epithelium becomes incorporated within the buccal
      aspect of the invaginating dental lamina to form part of the external enamel
      epithelium of the cap stage tooth germ. This locus of Hox-8 expression becomes
      continuous with new sites of Hox-8 expression in the enamel navel, septum, knot
      and internal enamel epithelium. The transitory enamel knot, septum and navel were
      postulated, long ago, to be involved in specifying tooth shape, causing the
      inflection of the first buccal cusp, but this theory has been largely ignored.
      Interestingly, in the conical incisor teeth, the enamel navel, septum and knot
      are absent, and Hox-8 has a symmetrical expression pattern. Our demonstration of
      the precise expression patterns of Hox-8 in the early dental placodes and their
      subsequent association with the enamel knot, septum and navel provide the first
      molecular clues to the basis of patterning in the dentition and the association
      of tooth position with tooth shape: an association all the more intriguing in
      view of the evolutionary robustness of the patterning mechanism, and the known
      role of homeobox genes in Drosophila pattern formation. At the bell stage of
      tooth development, Hox-8 expression switches tissue layers, being absent from the
      differentiating epithelial ameloblasts and turned on in the differentiating
      mesenchymal odontoblasts. Hox-7 is expressed in the mesenchyme of the dental
      papilla and follicle at all stages. This reciprocity of expression suggests an
      interactive role between Hox-7, Hox-8 and other genes in regulating epithelial
      mesenchymal interactions during dental differentiation.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1358590
TI  - Gonad formation and development requires the abd-A domain of the bithorax complex
      in Drosophila melanogaster.
AB  - The abdominal-A (abd-A) gene, a member of the bithorax complex, is required for
      the correct identity of parasegments (PS) 7 through 13. Mutations in iab-4, one
      of the cis-regulatory regions of abd-A, transform epidermal structures of PS 9
      and also cause loss of gonads in adult flies. Here, we describe a developmental
      and molecular analysis of the role of iab-4 functions in gonadal development. In
      flies homozygous for a strong iab-4 allele, gonadogenesis is not initiated in the
      embryo because the mesodermal cells fail to encapsulate the pole cells. Flies
      homozygous for weaker iab-4 mutations sometimes form ovaries. The ovary-oviduct
      junctions are abnormal, however, and egg transfer from the ovary to the uterus is
      blocked in the adult. To localize the sites that require iab-4 function, we have
      analyzed animals chimeric for the mutant and wild-type cells. These chimeras were
      generated by three kinds of transplantation experiments: pole cells, embryonic
      somatic nuclei or larval ovaries. Our results suggest that iab-4 is required in
      the somatic cells of the gonadal primordia, but not the germ line. In addition,
      the formation of functional ovary-oviduct junctions and egg transfer also
      requires iab-4 functions in the somatic cells of the ovary and in at least one
      additional somatic tissue.

PMID- 1358593
TI  - Respecification of vertebral identities by retinoic acid.
AB  - In higher vertebrates, the formation of the body axis proceeds in a craniocaudal
      direction during gastrulation. Cell biological evidence suggests that mesoderm
      formation and specification of axial positions occur simultaneously. Exposure of
      gastrulating embryos to retinoic acid induces changes in axial patterns, e.g.
      anterior and posterior homeotic transformations of vertebrae. These morphological
      changes are accompanied by changes in the nonidentical, overlapping expression
      domains of Hox genes. In this report the influence of retinoic acid, administered
      at the end of and after gastrulation, on vertebral patterns is described.
      Anterior transformations and truncations affecting the caudal part of the
      vertebral column characterize animals exposed on day 8 and 9. 4 hours after
      retinoic acid administration on day 8 + 5 hours, Hox-1.8, Hox-1.9, and Hox-4.5
      transcripts were not detected in their usual posterior expression domains,
      whereas transcripts of the anterior Hox-1.5 gene remained unaffected. 4 days
      after RA exposure on day 8 + 5 hours, Hox-1.8 expression was shifted posteriorly
      by an effectively low dose of RA, which induced the formation of supernumerary
      ribs. Hox-1.8 expression was limited to posterior, disorganized mesenchyme,
      bulging out neural tube, some intestinal loops and the hindlimb in truncated
      embryos exposed to a high dose of RA. A causal relation between the delayed
      activation of posterior Hox genes and anterior transformations or agenesis of
      vertebrae is discussed. On day 10.5 posterior transformations begin to occur in
      the cervical region, while later exposures again affect more caudal structures.
      The distribution of the transformations along the vertebral column indicates an
      influence of RA on migrating sclerotome cells before they are finally fixed in
      the cartilagenous vertebrae. The findings show that the mesodermal segments
      originally specified during gastrulation can be respecified in their second
      migratory phase, with effects spreading for a second time in a craniocaudal
      direction. The transformations are discussed with regard to a molecular
      specification of axial levels by Hox codes, defined as combinations of expressed
      Hox genes.

PMID- 1358592
TI  - Localized expression of a Xenopus POU gene depends on cell-autonomous
      transcriptional activation and induction-dependent inactivation.
AB  - We have cloned a cDNA encoding a Xenopus POU domain protein, XLPOU91, which is
      expressed at high levels in gastrula embryos. XLPOU91 transcription initiates at
      the midblastula transition, and declines to low levels by late neurula stages. In
      early neurula embryos, XLPOU91 transcripts are enriched 35-fold in the most
      ventroposterior versus anterior regions. Initial transcriptional activation of
      the gene is cell autonomous; the gene is activated in dissociated gastrula stage
      embryos as well as in animal cap explants. Cell-cell communication is needed for
      proper temporal down-regulation of XLPOU91 expression in late neurula embryos;
      cell dissociation during blastula stages or removal of explants from the embryo
      prevents normal transcriptional shunt down. Explants treated with peptide growth
      factors (PGFs) mimic the normal temporal and spatial shut down in whole embryos.
      This negative regulatory pathway may be important for determining cell fate or
      maintaining an inducible state in the ventroposterior region of the embryo.

PMID- 1358594
TI  - Hox-4 gene expression in mouse/chicken heterospecific grafts of signalling
      regions to limb buds reveals similarities in patterning mechanisms.
AB  - The products of Hox-4 genes appear to encode position in developing vertebrate
      limbs. In chick embryos, a number of different signalling regions when grafted to
      wing buds lead to duplicated digit patterns. We grafted tissue from the
      equivalent regions in mouse embryos to chick wing buds and assayed expression of
      Hox-4 genes in both the mouse cells in the grafts and in the chick cells in the
      responding limb bud using species specific probes. Tissue from the mouse limb
      polarizing region and anterior primitive streak respecify anterior chick limb bud
      cells to give posterior structures and lead to activation of all the genes in the
      complex. Mouse neural tube and genital tubercle grafts, which give much less
      extensive changes in pattern, do not activate 5'-located Hox-4 genes. Analysis of
      expression of Hox-4 genes in mouse cells in the grafted signalling regions
      reveals no relationship between expression of these genes and strength of their
      signalling activity. Endogenous signals in the chick limb bud activate Hox-4
      genes in grafts of mouse anterior limb cells when placed posteriorly and in
      grafts of mouse anterior primitive streak tissue. The activation of the same gene
      network by different signalling regions points to a similarity in patterning
      mechanisms along the axes of the vertebrate body.

PMID- 1358596
TI  - Role of the chicken homeobox-containing genes GHox-4.6 and GHox-8 in the
      specification of positional identities during the development of normal and
      polydactylous chick limb buds.
AB  - During early stages of normal chick limb development, the homeobox-containing
      (HOX) gene GHox-4.6 is expressed throughout the posterior mesoderm of the wing
      bud from which most of the skeletal elements including the digits will develop,
      whereas GHox-8 is expressed in the anterior limb bud mesoderm which will not give
      rise to skeletal elements. In the present study, we have examined the expression
      of GHox-4.6 and GHox-8 in the wing buds of two polydactylous mutant chick
      embryos, diplopodia-5 and talpid2, from which supernumerary digits develop from
      anterior limb mesoderm, and have also examined the expression of these genes in
      response to polarizing zone grafts and retinoic acid-coated bead implants which
      induce the formation of supernumerary digits from anterior limb mesoderm. We have
      found that the formation of supernumerary digits from the anterior mesoderm in
      mutant and experimentally induced polydactylous limb buds is preceded by the
      ectopic expression of GHox-4.6 in the anterior mesoderm and the coincident
      suppression of GHox-8 expression in the anterior mesoderm. These observations
      suggest that the anterior mesoderm of the polydactylous limb buds is
      "posteriorized" and support the suggestion that GHox-8 and GHox-4.6,
      respectively, are involved in specifying the anterior non-skeletal and posterior
      digit-forming regions of the limb bud. Although the anterior mesodermal domain of
      GHox-8 expression is severely impaired in the mutant and experimentally induced
      polydactylous limb buds, this gene is expressed by the prolonged, thickened
      apical ectodermal ridges of the polydactylous limb buds that extend along the
      distal anterior as well as the distal posterior mesoderm.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1358595
TI  - The expression of neuropeptide Y immunoreactivity in the avian sympathoadrenal
      system conforms with two models of coexpression development for neurons and
      chromaffin cells.
AB  - We have studied the expression and development of neuropeptide Y-like
      immunoreactivity (NPY-LI) in the sympathoadrenal system of the chicken using
      single and double immunocytochemical techniques and radioimmunoassay. NPY-LI is
      expressed by neurons of the paravertebral sympathetic ganglia and by chromaffin
      cells of the adrenal gland in embryonic and adult chickens. The peptide is
      coexpressed with catecholaminergic properties in neurons. In chromaffin cells, it
      is also expressed with immunoreactivity to somatostatin and serotonin. We have
      used the expression of NPY-LI to analyze how cells that coexpress two or more
      neuroactive substances arrive at their final phenotype. Our results suggest that
      the ontogeny of coexpression in neurons of the avian paravertebral sympathetic
      ganglia occurs in a sequential pattern, where the expression of the peptide
      follows the initial expression of the "classical neurotransmitter". In contrast,
      in chromaffin cells, expression of the peptides occurs concomitantly with
      expression of catecholaminergic properties or soon after. Initially, coexpression
      of several neuroactive substances occurs, but this is followed by further
      specialization where the expression of one peptide prevails over the other. We
      believe that the two models of coexpression shown by our results can be used to
      describe the ontogeny of coexpression in other cells of the nervous system.

PMID- 1358598
TI  - Relaxation of soman-induced contracture of airway smooth muscle in vitro.
AB  - A possible role for beta-adrenergic agonists in the management of
      bronchoconstriction resulting from exposure to anticholinesterase compounds was
      investigated in vitro in canine tracheal smooth muscle. Norepinephrine,
      salbutamol and isoproterenol produced partial relaxation of soman-induced
      contractures. However, the relaxation induced was not sustained; muscle tensions
      returned to pretreatment levels within minutes despite the continued presence of
      beta-agonists. Increasing cAMP levels with the non beta-agonist bronchodilators
      such as theophylline, a phosphodiesterase inhibitor, or forskolin, a specific
      stimulator of adenylate cyclase, resulted in more complete and longer lasting
      relaxation, suggesting that beta-adrenoceptor desensitization may contribute to
      the failure by beta-agonists to produce sustained relaxation.

PMID- 1358597
TI  - Mechanism of skin morphogenesis. II. Retinoic acid modulates axis orientation and
      phenotypes of skin appendages.
AB  - The factors that determine the axial orientation and phenotypes of skin
      appendages were analyzed by studying the effect of retinoic acid (RA) on
      embryonic chicken skin explant cultures. With RA uniformly distributed in the
      culture media, the feather buds became smaller, were disoriented or were
      transformed into scale-like structures in a concentration-dependent manner (from
      0.05-2.5 microM). With RA distributed as a gradient created by a RA-soaked anion
      exchange bead, a radial zone of inhibition with a rim of disoriented buds was
      observed. The new axis of the disoriented buds appeared to be determined by a
      combination of the original feather axis determining force and a new axial force
      pointing centrifugally away from the RA source. This observed result can be
      simulated with a computer model using a vectorial sum of different feather axial
      determination forces. The size of the inhibited zone is linearly correlated to
      the RA concentration and may be used to quantify the morphogenetic activity of
      retinoids. These effects are specific to developmental stages (Hamburg and
      Hamilton stage 31-34). Both all-trans and 13-cis RA have morphogenetic activity.
      Retinol has no effect and retinal has a small inhibitory effect but neither
      phenotypic transformation nor axial disorientation were observed. The antero
      posterior gradient of homeoprotein XlHbox 1 in feather buds became diffusive
      after RA treatment. RA dissolves dermal condensations and the distribution of N
      CAM is altered from an anterior localized pattern to a diffusive presence in the
      bud cores. Endogenous retinoids in developing skins show developmental stage
      dependent changes both quantitatively and qualitatively. The results suggest that
      RA either is or can modulate the endogenous morphogen(s) that determine the
      orientation and phenotype of skin appendages, and that this morphogenetic pathway
      involves Hox genes and adhesion molecules.

PMID- 1358599
TI  - Special wounds. Nail bed, plantar puncture, and cartilage.
AB  - Traumatic wounds are one of the most common problems encountered in the practice
      of emergency medicine. The literature is replete with articles concerning the
      evaluation and care of life threatening wounds, but many common non-life
      threatening injuries have received very little attention. This article focuses on
      nail bed injuries, plantar puncture wounds, and cartilaginous wounds. Although
      not immediately life threatening, these injuries may be associated with
      significant long-term morbidity and, rarely, life threatening sequelae.

PMID- 1358600
TI  - Remembrance: the discovery of growth hormone (GH)-releasing hormone and GH
      release-inhibiting hormone.

PMID- 1358601
TI  - A pituitary specific point mutation of codon 201 of the Gs alpha gene in a
      pituitary adenoma of a patient with multiple endocrine neoplasia (MEN) type 1.
AB  - The DNA from a pituitary adenoma of a patient with multiple endocrine neoplasia
      (MEN) type 1 was analyzed to detect a point mutation of the Gs alpha gene (gsp)
      by the PCR direct-sequencing method. The patient had galactorrhea, amenorrhea and
      acromegalic features. Hormonal examination revealed high serum levels of PRL and
      GH. The tumor was histologically diagnosed as a mixed GH cell-PRL cell adenoma in
      which GH and PRL were produced by different cells. Sequence analysis of the DNAs
      extracted from paraffin sections of pituitary, parathyroid, and pancreas tumors
      demonstrated the substitution of thymidine for cytidine in codon 201 of the Gs
      alpha gene that resulted in replacement of arginine (CGT) with cysteine (TGT)
      only in the pituitary adenoma, but not in the parathyroid and pancreas tumors.
      These results suggest that a pituitary specific point mutational activation of
      the Gs alpha gene may be involved in the development of the pituitary adenoma in
      this patient.

PMID- 1358602
TI  - Laparoscopy in the Diagnosis and Treatment of Abdominal Disease. Proceedings of
      the Orlando Symposium, 20-21 January 1992.

PMID- 1358603
TI  - Epilepsy through life: recent advances in understanding and treating epilepsy
      during pregnancy, childhood, adulthood, and old age. Proceedings of the 11th
      annual Merritt-Putnam Symposium.

PMID- 1358604
TI  - Calculation of restriction fragment lengths by image processing.
AB  - The image processing system, LabEye Profile, calculates the size of DNA
      restriction fragments according to the formula MD = f(x); x = 1/log bp. The
      migration distances (MD) of known fragment sizes are interpolated by the use of
      cubic splines. Cubic splines are also used to correct for gel distortions. A
      comparison to the Biotrac system, which uses the reciprocal method, gives almost
      identical standard deviations for calculated sizes compared to known sizes, 0.88%
      for LabEye Profile and 0.89% for Biotrac. The measurement error for LabEye
      Profile is 0.24% of the size of the fragments.

PMID- 1358606
TI  - Ondansetron in postoperative nausea and vomiting. Proceedings of a symposium.
      London, 28 February 1992.

PMID- 1358605
TI  - Development and function of T cells in mice with a disrupted CD2 gene.
AB  - CD2 is a T cell surface glycoprotein that mediates cellular adhesion and can
      participate in signal transduction. It is expressed early in thymocyte ontogeny
      and consequently has been proposed to participate in T cell development. To study
      the in vivo function of CD2, the murine gene was inactivated using the technique
      of homologous recombination in embryonic stem cells. Homozygous mutant mice are
      healthy and have an apparently normal complement of lymphocytes. They mount
      effective immune responses similar to those of wild type controls. In particular,
      the generation and function of cytotoxic T cells was found to be normal as was
      the production of antibodies following immunization. Selection of thymocytes
      expressing either MHC class I- or class II-restricted transgenic T cell receptors
      was also grossly normal in the absence of CD2. Thus, CD2 may be dispensable for
      the development and function of T cells. Within the context of other targetted
      mutations, these mice should be useful in defining the precise roles of various
      cell surface molecules involved in T cell responses.

PMID- 1358607
TI  - Oral ondansetron in the prevention of postoperative nausea and vomiting.
AB  - The effect of three times daily oral ondansetron in preventing postoperative
      nausea and vomiting was investigated in two randomized, double-blind, placebo
      controlled, multi-centre studies. The first study compared ondansetron 1, 8 and
      16 mg to placebo, and the second study compared 8 mg ondansetron to placebo. Both
      studies included ASA Class I-III female patients about to undergo major abdominal
      gynaecological surgery or vaginal hysterectomy. In the first study, the 8 and 16
      mg ondansetron groups had a significantly lower incidence of nausea and vomiting
      in the 0-24 h period following recovery from anaesthesia than the placebo group.
      Ondansetron 8 mg three times daily was also significantly better than placebo in
      the second study. Side-effects mainly consisted of constipation, headache, and
      asymptomatic elevation of liver enzymes. The incidence of side-effects was
      similar in ondansetron- and placebo-treated patients. There appeared to be no
      clinically important benefit of the 16 mg three times daily ondansetron regimen
      over the 8 mg three times daily dose, therefore 8 mg three times daily is
      recommended as the optimal oral dose in the prevention of postoperative nausea
      and vomiting.

PMID- 1358608
TI  - Structures and functions of the sugar chains of glycoproteins.
AB  - Most proteins within living organisms contain sugar chains. Recent advancements
      in cell biology have revealed that many of these sugar chains play important
      roles as signals for cell-surface recognition phenomena in multi-cellular
      organisms. In order to elucidate the biological information included in the sugar
      chains and link them with biology, a novel scientific field called 'glycobiology'
      has been established. This review will give an outline of the analytical
      techniques for the structural study of the sugar chains of glycoproteins, the
      structural characteristics of the sugar chains and the biosynthetic mechanism to
      produce such characteristics. Based on this knowledge, functional aspects of the
      sugar chains of glycohormones and of those in the immune system will be described
      to help others understand this new scientific field.

PMID- 1358609
TI  - Proteolytic cleavage of atrial natriuretic factor receptor in bovine adrenal
      membranes by endogenous metalloendopeptidase. Effects on guanylate cyclase
      activity and ligand-binding specificity.
AB  - Atrial natriuretic factor (ANF) is a peptide hormone from the heart atrium with
      potent natriuretic and vasorelaxant activities. The natriuretic activity of ANF
      is, in part, mediated through the adrenal gland, where binding of ANF to the 130
      kDa ANF receptor causes suppression of aldosterone secretion. Incubation of
      bovine adrenal membranes at pH < 5.6 caused a rapid and spontaneous cleavage of
      the 130-kDa ANF receptor, yielding a 65-kDa polypeptide that could be detected by
      photoaffinity labeling by 125I-labeled N alpha 4-azidobenzoyl-ANF(4-28) followed
      by SDS/PAGE under reducing conditions. Within 20 min of incubation at pH 4.0,
      essentially all the 130-kDa receptor was converted to a 65-kDa ANF binding
      protein. This cleavage reaction was completely inhibited by inclusion of 5 mM
      EDTA. When SDS/PAGE was carried out under non-reducing conditions, the apparent
      size of the ANF receptor remained unchanged at 130 kDa, indicating that the 65
      kDa ANF-binding fragment was still linked to the remaining part(s) of the
      receptor polypeptide through a disulfide bond(s). The disappearance of the 130
      kDa receptor was accompanied by a parallel decrease in guanylate cyclase activity
      in the membranes. Inclusion of EDTA in the incubation not only prevented cleavage
      of the 130-kDa receptor, but also protected guanylate cyclase activity,
      indicating that proteolysis, but not the physical effects of the acidic pH,
      causes inactivation of guanylate cyclase. The 130-kDa ANF receptor in adrenal
      membranes was competitively protected from photoaffinity labeling by ANF(1-28) or
      ANF(4-28), but not by atriopeptin I [ANF(5-25)] or C-ANF [des-(18-22)-ANF(4-23)
      NH2]. On the contrary, the 65-kDa ANF-binding fragment generated after incubation
      at pH 4.0 was protected from labeling by any of the above peptides, indicating
      broader binding specificity. After incubation in the presence of EDTA, the 130
      kDa ANF receptor, which was protected from proteolysis, retained binding
      specificity identical to that of the 130-kDa receptor in untreated membranes. The
      results indicate that the broadening of selectivity is caused by cleavage, but
      not by the physical effect of acidic pH. Spontaneous proteolysis of ANF receptor
      by an endogenous metalloendopeptidase, occurring with concomitant inactivation of
      guanylate cyclase activity and broadening of ligand-binding selectivity, may be
      responsible for the generation of low-molecular-mass receptors found in the
      adrenal gland and other target organs of ANF. The proteolytic process may play a
      role in desensitization or down-regulation of the ANF receptor.

PMID- 1358610
TI  - Structural relationship between the hexameric and tetrameric family of glutamate
      dehydrogenases.
AB  - The family of glutamate dehydrogenases include a group of hexameric oligomers
      with a subunit M(r) of around 50,000, which are closely related in amino acid
      sequence and a smaller group of tetrameric oligomers based on a much larger
      subunit with M(r) 115,000. Sequence comparisons have indicated a low level of
      similarity between the C-terminal portion of the tetrameric enzymes and a
      substantial region of the polypeptide chain for the more widespread hexameric
      glutamate dehydrogenases. In the light of the solution of the three-dimensional
      structure of the hexameric NAD(+)-linked glutamate dehydrogenase from Clostridium
      symbiosum, we have undertaken a detailed examination of the alignment of the
      sequence for the C-terminal domain of the tetrameric Neurospora crassa glutamate
      dehydrogenase against the sequence and the molecular structure of that from C.
      symbiosum. This analysis reveals that the residues conserved between these two
      families are clustered in the three-dimensional structure and points to a
      remarkably similar layout of the glutamate-binding site and the active-site
      pocket, though with some differences in the mode of recognition of the nucleotide
      cofactor.

PMID- 1358611
TI  - Evidence for a protein kinase cascade in higher plants. 3-Hydroxy-3
      methylglutaryl-CoA reductase kinase.
AB  - Protein phosphorylation is well established as a regulatory mechanism in higher
      plants, but only a handful of plant enzymes are known to be regulated in this
      manner, and relatively few plant protein kinases have been characterized. AMP
      activated protein kinase regulates key enzymes of mammalian fatty acid, sterol
      and isoprenoid metabolism, including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG
      CoA) reductase. We now show that there is an activity in higher plants which, by
      functional criteria, is a homologue of the AMP-activated protein kinase, although
      it is not regulated by AMP. The plant kinase inactivates mammalian HMG-CoA
      reductase and acetyl-CoA carboxylase, and peptide mapping suggests that it
      phosphorylates the same sites on these proteins as the mammalian kinase. However,
      with the target enzymes purified from plant sources, it inactivates HMG-CoA
      reductase but not acetyl-CoA carboxylase. The kinase is located in the soluble,
      and not the chloroplast, fraction of leaf cells, consistent with the idea that it
      regulates HMG-CoA reductase, and hence isoprenoid biosynthesis, in vivo. The
      plant kinase also appears to be part of a protein kinase cascade which has been
      highly conserved during evolution, since the kinase is inactivated and
      reactivated by mammalian protein phosphatases (2A or 2C) and mammalian kinase
      kinase, respectively. This contrasts with the situation for many other mammalian
      protein kinases involved in signal transduction, which appear to have no close
      homologue in higher plants. To our knowledge, this represents the first direct
      evidence for a protein kinase cascade in higher plants.

PMID- 1358612
TI  - Molecular epidemiological analysis of Pseudomonas aeruginosa strains causing
      failure of antibiotic therapy in cystic fibrosis patients.
AB  - A combination of esterase electrophoretic typing and analysis of the restriction
      fragment length polymorphism of ribosomal DNA regions (ribotyping) was used to
      compare 27 Pseudomonas aeruginosa strains isolated before and after two-week
      courses of anti-pseudomonal treatment in seven cystic fibrosis patients. A total
      of 12 courses of therapy were studied in which ciprofloxacin, ceftazidime,
      azlocillin or imipenem were used alone or in combination with tobramycin.
      Isolates at a count of greater than or equal to 10(6) cfu/ml of sputum were
      collected when there was evidence of therapeutic failure on the basis of
      persistence of isolates whether or not they were resistant to the antibiotic used
      for therapy. Emergence of resistance was observed in ten cases and failure to
      eradicate sensitive strains in five cases. Among the 27 isolates, eight zymotypes
      and five ribotypes were identified. With this typing approach, resistant post
      therapy isolates were found to be identical to pre-therapy isolates in all cases
      but one. However, in one case an additional resistant strain was isolated after
      therapy besides that initially present. In all five cases in which susceptibility
      was still observed after treatment, pre-therapy and post-therapy isolates were
      indistinguishable. Using this molecular typing approach, all the strains were
      typable. Thus combination of esterase typing and ribotyping should improve the
      analysis of therapeutic failure in cystic fibrosis patients.

PMID- 1358613
TI  - Visualization of posture-dependent cerebral blood flow in a patient with
      Takayasu's disease by means of 99mTc-HMPAO brain single photon emission
      tomography.
AB  - A case of Takayasu's disease in a 22-year-old woman who complained of severe
      fainting attacks is presented. Bilateral obstruction of the cervical arteries was
      confirmed by digital subtraction angiography. Preoperative technetium-99m
      hexamethylpropylene amine oxime brain SPET in the sitting position showed
      bilateral hypoactivity in the temporoparietal areas. Subtraction brain SPET
      showed slightly increased activity in the lying position. The patient has had no
      fainting attacks since bypass surgery. Postoperative 99mTc-HMPAO brain SPET in
      the sitting position showed normal activity except in the right temporoparietal
      area. This area was filled in the lying position. 99mTc-HMPAO brain SPET is the
      only technique that can visualize the cerebral blood flow in any position, this
      capability deriving on the fact that the distribution of 99mTc-HMPAO in the brain
      is fixed in the first 2-3 min following injection. The use of both sitting and
      lying 99mTc-HMPAO brain SPET is very useful for detecting an abnormality (i.e. an
      inhomogeneous response due to the fall in perfusion pressure) that could not be
      seen if the cerebral blood flow were to be assessed only in the lying position.

PMID- 1358614
TI  - Drug therapy of Parkinson's disease. An overview.
AB  - The nation-wide collaborative study on the bromocriptine monotherapy and
      bromocriptine-levodopa combination therapy was completed in November 1990, and
      the results were reported during the symposium on the Long-Term Treatment of
      Parkinson's Disease held in Tokyo in October 1991. The author briefly reviewed
      the history of treatment of Parkinson's disease, and current and future trends in
      its drug therapy as an introductory remark. The personal view on the principle of
      drug treatment for parkinsonian patients is the judicious concomitant use of
      several different classes of anti-parkinsonian drugs, including levodopa,
      dopamine agonists, monoamine oxidase inhibitors, anticholinergics, and amantadine
      HCl utilizing the smallest effective dose for each drug. The treatment of
      Parkinson's disease seems to be moving slowly from mere symptomatic therapy to
      the one which is aiming the protection of nigral cells. Recent progress in this
      field is also briefly reviewed.

PMID- 1358616
TI  - Markers in urology. Proceedings of the 2nd Mediterranean Congress of Urology.
      Rome, Italy, July 3-6, 1991.

PMID- 1358615
TI  - Early therapy for Parkinson's disease.
AB  - The management of patients with early Parkinson's disease should now take into
      account the possibility that MAO-B inhibitors may provide neuroprotective
      therapy, that dopamine undergoes oxidative metabolism and has the potential to
      generate cytotoxic free radicals, and that the early employment of drugs which
      provide sustained central dopamine agonism may delay the development of adverse
      effects associated with chronic levodopa therapy. The aim of treatment for
      patients with early Parkinson's disease is to utilize strategies designed to
      address these issues without compromising clinical control. These approaches are
      reviewed.

PMID- 1358617
TI  - DNA-ploidy, morphometric-stereological and P-glycoprotein study of superficial
      bladder carcinomas.
AB  - We carried out a DNA-ploidy, morphometric-stereologic and P-glycoprotein study on
      40 newly diagnosed superficial bladder cancer patients (G1-G2), correlating the
      results with histological grade and clinical outcome. Variations in the number of
      patients who present recurrences, progression or remain tumor-free during the
      whole follow-up period (at least 5 years) were not significant when related to
      nuclear size, proliferative diploid index, presence of aneuploidy and expression
      of P-glycoprotein. It is striking how the majority of disease-free subjects
      showed a proliferative diploid index higher than 10%. Moreover, 3 of them
      presented an aneuploid cell population. In our study, only histological grade
      showed a significant discriminatory level in terms of progression versus no
      progression in patients with superficial bladder cancer.

PMID- 1358618
TI  - Characterization of seven kidney tumors by flow cytometry: analysis of cell
      cycle, DNA content and P-glycoprotein expression.
AB  - Seven kidney tumors obtained from patients aged from 5 to 76 years were analyzed
      by flow cytometry for cell cycle, DNA content and P-glycoprotein expression
      involved in multidrug resistance. The DNA index seems to be an important
      criterion since all the tumors were aneuploid. In a case of clear cell carcinoma,
      two aneuploid clones were identified. In 5 cases of kidney tumors a high
      proportion of cells in proliferation (S + (G2 + M)) was observed; it was
      comprised between 13 and 33%. As for P-glycoprotein it was detected only in few
      tumor cells (5-15%) respectively in a case of clear cell carcinoma and in a case
      of Wilms' tumor.

PMID- 1358619
TI  - Graves' immunoglobulins and cytokines stimulate the expression of intercellular
      adhesion molecule-1 (ICAM-1) in cultured Graves' orbital fibroblasts.
AB  - Intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-asociated
      antigen-1 (LFA-1) are cell surface adhesion receptors that bind to one another
      and promote a variety of effector/target cell interactions in tissues affected by
      inflammatory or immune processes. Local infiltration of the thyroid gland and the
      retro-ocular space by mononuclear cells is a hallmark of Graves' disease and
      Graves' ophthalmopathy (GO). Thus, we studied the role of these adhesion
      receptors in the interaction of inflammatory cells with retro-ocular fibroblasts
      (OF) derived from patients undergoing transantral decompression for severe GO,
      and from normal individuals. Confluent OF-monolayers were incubated with various
      cytokines or protein-A affinity-purified IgGs prepared from sera of patients with
      severe GO, Hashimoto's thyroiditis (HT), rheumatoid arthritis (RA) and normal
      individuals. As determined by immunocytochemistry and immunoprecipitation using a
      monoclonal anti-ICAM-1 antibody, interleukin-1-alpha (IL-1a), tumour necrosis
      factor-alpha (TNFa) and interferon-gamma (IFNg) strongly enhanced surface
      expression of ICAM-1 in both GO- and normal OF. By contrast, Graves' IgGs
      stimulated ICAM-1 expression only in GO-, but not in normal OF. No effect was
      observed in either cell type with interleukin-2, transforming growth factor-beta,
      or IgGs from patients with HT, RA and normal individuals. Using phorbol ester
      activated, 51Cr-labelled peripheral blood mononuclear cells (PBMCs) in a cell
      adhesion assay, we demonstrated potent adhesive activity of ICAM-1 in GO-OF
      pretreated with IL-1a, TNFa, IFNg or Graves' IgGs, while all other compounds did
      not affect PBMC adhesion to GO-OF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358620
TI  - Lack of pharmacodynamic and pharmacokinetic interactions of the antihistamine
      ebastine with ethanol in healthy subjects.
AB  - We have given 12 healthy subjects the H1-antihistamine ebastine (20 mg) or
      placebo in a double-blind, crossover study for one week each. The subjects were
      tested for drug effects on Day 6 of each period, and for interactions of ebastine
      with ethanol (0.8 g.kg-1) on Day 7. On both days, the testing runs were done at
      baseline and at 2, 4, and 6 h after the drug. Performance was evaluated both
      objectively (digit symbol substitution, flicker fusion, Madox wing, nystagmus,
      simulated driving, body balance) and subjectively (visual analogue scales) and
      with questionnaires. Venous blood samples were taken daily during maintenance and
      during each test run for assay of plasma carebastine. Blood ethanol
      concentrations were assayed with an Alcolmeter in the breath and directly in the
      blood. Plasma carebastine concentration reached a steady-state from Day 3 on; the
      mean concentrations in the morning were 92 micrograms.l-1 on Day 6 and 104
      micrograms.l-1 on Day 7. The rise in plasma carebastine after an extra 20 mg of
      ebastine was accelerated but not increased by ethanol. Ebastine did not impair
      performance objectively or subjectively. It slightly improved body balance and
      reduced errors during simple tracking at 4 h. Blood ethanol concentrations peaked
      (mean 0.76 g.l-1) at 1.5 h after ethanol intake. Ethanol impaired performance in
      most objective tests and produced clumsiness, muzziness, and mental slowness, but
      little drowsiness. Ebastine neither modified the blood ethanol concentrations nor
      increased the effects of ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358621
TI  - Comparing risk estimates of sulphonamide-induced agranulocytosis from the Swedish
      Drug Monitoring System and a case-control study.
AB  - A comparison has been made of risk estimates for agranulocytosis connected with
      sulphasalazine and trimethoprim-sulphamethoxazole (T-SM) therapy calculated from
      data in the Swedish Drug Monitoring System ("spontaneous" reports, sales and
      prescription information) and a population based case-control study (the IAAAS).
      The relative risk for agranulocytosis during sulphasalazine treatment was
      calculated to be 107 and 123 by the spontaneous reporting system and the case
      control study, respectively. The corresponding excess risk in both systems was
      1.8. For T-SM the relative risk was 17 in the spontaneous reporting system and 12
      in the case-control study, while the excess risk calculated for 3 days of
      treatment was 0.9 in the spontaneous reporting system, and 1.6 for 3 or more days
      of treatment in the case-control study. It is concluded that the Swedish Drug
      Monitoring System gives an appropriate estimate of the risk of developing
      agranulocytosis in association with the two drugs studied.

PMID- 1358622
TI  - Sulfasalazine associated agranulocytosis in Sweden 1972-1989. Clinical features,
      and estimation of its incidence.
AB  - During the 18 year period 1972-1989 a total of 62 cases of agranulocytosis
      associated with the use of sulphasalazine were reported to the Swedish Adverse
      Drug Reactions Advisory Committee (SADRAC). The median age of the patients was 52
      y and median duration of sulphasalazine treatment was 43 days. The fatality rate
      was 6.5%, and among patients who recovered the median recovery time was 10 days.
      Twelve patients were treated concomitantly with other drugs generally suspected
      to induce agranulocytosis. From sales and prescription data the average incidence
      of agranulocytosis during sulphasalazine therapy was estimated to be 1/1750
      patient years of exposure. From an ongoing Prescription Monitoring Project in a
      Swedish county it was possible to calculate the proportion of patients receiving
      sulphasalazine for different periods of time. The incidence of agranulocytosis
      during the first 30 days was estimated to be 1/2400 patients, while it was 1/700
      between Days 31-90 and 1/11200 during Days 91-365. The risk of developing
      agranulocytosis during sulphasalazine treatment is considerable during the first
      three months of treatment, and the traditional way of expressing the risk (1/1750
      patient years) underestimates the risk for the individual patient.

PMID- 1358623
TI  - Differential thymus dependence of rat CD8 isoform expression.
AB  - Expression of the rat CD8 molecule was studied using five novel monoclonal
      antibodies (mAb), four of which are specific for the V-like domain of CD8 alpha,
      whereas one reacts either with the beta chain or with a determinant only
      expressed on the CD8 alpha/beta heterodimer. mAb to both chains effectively
      blocked purified lymph node CD8 T cells in mixed lymphocyte reaction and in cell
      mediated cytotoxicity. Flow cytometric analysis showed that CD8 T cells from
      lymph nodes or spleen of normal rats almost exclusively express the alpha/beta
      isoform, regardless of the T cell receptor isotype (alpha/beta or gamma/delta).
      In contrast, natural killer (NK) cells carry only CD8 alpha chains. This CD8
      alpha + beta - phenotype was also prominent among CD8 T cells from athymic rats
      and from intestinal epithelium of normal rats. CD8 alpha homodimers can also be
      expressed as a result of activation, as shown by analysis of CD4 CD8 double
      positive T cells obtained from highly purified lymph node CD4 T cells by in
      vitrok stimulation. Such CD4+CD8 alpha + beta - cells also represent a major
      subset among adult intestinal intraepithelial lymphocytes (IEL), suggesting local
      activation. Taken together, the difference in CD8 isoform expression among T
      cells from athymic rats, NK cells, and gut IEL versus CD8 T cells from peripheral
      lymphatic organs of euthymic animals suggests that like in mice, expression of
      the CD8 heterodimer is more dependent on intrathymic maturation than that of the
      homodimer. Since the more stringent thymus dependence of CD8 alpha + beta + T
      cells may be due to a requirement for thymic selection on self major
      histocompatibility complex class I antigens, the virtually exclusive CD8 alpha +
      beta + phenotype of peripheral rat gamma/delta T cells could mean that antigen
      recognition by this subset is also restricted by MHC class I molecules.

PMID- 1358624
TI  - Interleukin-4 differentially regulates interleukin-2-mediated and CD2-mediated
      induction of human lymphokine-activated killer effectors.
AB  - Natural killer (NK) cells can be differentiated into lymphokine-activated killer
      (LAK) effectors following stimulation with interleukin (IL)-2. This induction can
      be negatively regulated by IL-4. In this study, we demonstrate that the
      stimulation of NK cells through the CD2 pathway with (9-1 + 9.6) monoclonal
      antibodies can also induce these cells to secrete tumor necrosis factor-alpha
      (TNF-alpha) and to differentiate into LAK effectors. More importantly, our data
      indicate that, in contrast to the IL-2-induced LAK generation, the anti-CD2
      triggered LAK activity was not regulated by IL-4. IL-4 was found to enhance the
      LAK activity as well as NK cell proliferation following activation with anti-CD2
      by a mechanism involving, at least in part, an increased TNF-alpha production.
      Using immobilized monoclonal antibodies against the Fc receptor (Fc gamma RIII or
      CD16) for NK stimulation, we also observed that the anti-CD16-induced LAK
      activity was not inhibited by IL-4. These data further point to a pivotal role of
      TNF-alpha as a regulatory cytokine in anti-CD2-induced LAK generation, and
      suggest that IL-4 could serve as a discriminatory factor between two distinct
      pathways involved in the activation of non-MHC-restricted cytotoxicity.

PMID- 1358625
TI  - Both T cell receptor (TcR)-CD3 complex and CD2 increase the tyrosine kinase
      activity of p56lck. CD2 can mediate TcR-CD3-independent and CD45-dependent
      activation of p56lck.
AB  - T cell activation by triggering the T cell receptor (TcR)-CD3 complex leads to a
      dramatic increase in tyrosine phosphorylation of multiple cellular proteins. To
      date, there has been no direct evidence on the identity of the tyrosine kinase
      activity implicated in this signaling pathway. In this study, we demonstrate that
      activation of human T cells with anti-CD3 monoclonal antibody increases tyrosine
      kinase activity of p56lck. This extends our previous findings which demonstrated
      the involvement of p56lck kinase activity in the CD2 signal transduction pathway.
      The results from peripheral blood lymphocytes and Jurkat cell line showed in both
      cases an early and transient change in the specific activity of p56lck, followed
      by a shift to a higher apparent molecular mass. Therefore, to test directly the
      role of TcR-CD3 in CD2-induced activation of p56lck, we utilized mutant variants
      of the Jurkat cell line lacking in cell surface TcR-CD3. We found that cell
      surface expression of TcR-CD3 is not required for the activation of p56lck via
      CD2 but is necessary for the appearance of the reduced-electrophoretic-mobility
      form of p56lck observed after CD2 triggering. By isolating CD45- mutants from
      Jurkat cells, we observed that surface expression of the tyrosine phosphatase
      CD45 is required in order to increase p56lck activity following CD2 stimulation,
      while CD4-induced activation of the kinase remained unchanged. These data provide
      evidence for a specific functional linkage between CD2 and p56lck, in which CD45
      may play an essential role.

PMID- 1358626
TI  - Human neutrophils release their major membrane sialoprotein, leukosialin (CD43),
      during cell activation.
AB  - Leukosialin (CD43) is a sialic acid-rich molecule with a relative molecular mass
      (M(r)) of 140,000 highly represented on polymorphonuclear neutrophils (PMN) and
      on most leukocytes. One of its functions may be to prevent nonspecific cell-to
      cell interactions through negative charge repulsions. As tested by
      immunofluorescence, neutrophil CD43 membrane expression was shown to decrease by
      up to 80% upon cell activation by phorbol myristate acetate (10 ng/ml) or by N
      formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 10(-6) M) in the presence of
      cytochalasin B. The kinetic of this decrease paralleled that of CD11b up
      regulation. FMLP alone, tumor necrosis factor (TNF-alpha), lipopolysaccharide and
      granulocyte macrophage colony-stimulating factor had moderate or insignificant
      effects, while inducing striking CD11b up-regulation. Cell priming with TNF-alpha
      followed by FMLP stimulation resulted in up to 40% decrease of CD43 expression.
      Anti-CD43 mAb immunoprecipitated three fragments of M(r) 130,000, 49,000 and
      34,000 from the cell-free supernatant of activated neutrophils, suggesting that
      CD43 is released from the membrane by proteolysis. Indeed, the decrease in CD43
      expression was inhibited by phenylmethanesulfonylfluoride (PMSF). Homotypic
      aggregation of activated PMN was also inhibited by PMSF and could result, at
      least in part, from the shedding of CD43. The shedding of such a strongly anionic
      and major membrane protein should drastically modify PMN surface charge and may
      allow previously hindered interactions by exposing new adhesion molecules.

PMID- 1358627
TI  - Suppressive effect of the dopamine D2 receptor agonist B-HT 920 on rat grooming.
AB  - The effect of the D2 agonist B-HT 920 was examined on three behavioural models of
      induced grooming in the rat. B-HT 920 potently inhibited the grooming elicited by
      a novel environment, whereas it stimulated the stretching-yawning syndrome.
      Pretreatment with the selective dopamine D2 receptor antagonist, sulpiride,
      reversed the phenomenon. When B-HT 920 was administered to rats before water
      immersion, it similarly antagonized total grooming; wet-dog shakes, detected in
      these same animals, were potently inhibited. Finally, B-HT 920 displayed
      inhibitory activity towards adrenocorticotropin hormone-induced excessive
      grooming. On the basis of these effects, the role of D2 receptor subtypes in the
      modulation of grooming is discussed.

PMID- 1358628
TI  - Vascular alpha-adrenoceptor affinity variation is not due to varying populations
      of subtypes distinguished by WB 4101 and chlorethylclonidine.
AB  - Interaction with chlorethylclonidine has been used to subdivide populations of
      alpha 1-adrenoceptors in some tissues. WB 4101 can distinguish high and low
      affinity states of the receptor. The present study was carried out to determine
      if different populations or affinity states of alpha 1-adrenoceptors
      distinguished by either of these compounds, could explain the variation in alpha
      1-adrenoceptor agonist affinity found amongst rabbit arteries. Five arteries were
      studied whose affinity for noradrenaline vary between 4.8 and 6.4. These were the
      thoracic aorta, renal, superior mesenteric, ear and ovarian arteries. WB 4101 was
      found to be equally effective in antagonizing noradrenaline on all arteries.
      Chlorethylclonidine caused a 20-fold rightward shift of the noradrenaline dose
      contraction curve in the thoracic aorta; but had little or no effect on the other
      vessels. Thus, the combination of different proportions of subsets of alpha 1
      adrenoceptors distinguished by WB 4101 or chlorethylclonidine does not explain
      the variation in alpha 1-adrenoceptor affinity found in these rabbit arteries.

PMID- 1358629
TI  - Interference of antihistamines and anti-allergic drugs with antigen-induced paw
      edema in boosted and unboosted mice.
AB  - The protective effects of two antihistamines and two anti-allergic drugs against
      anaphylactic paw edema were studied in immunized animals that had or had not
      received a booster injection of antigen. The injection of 1 or 10 micrograms/paw
      ovalbumin induced acute paw edema of similar intensity in both groups. The
      antihistamine meclizine and the mixed anti histamine/anti-5-HT antagonist
      cyproheptadine reduced the anaphylactic reaction by 55 and 84% respectively, in
      non-boosted animals and were less effective against edema induced by 1 microgram
      antigen in boosted animals. The effectiveness of these drugs was also reduced
      when boosted mice were challenged with 10 micrograms antigen, where meclizine and
      cyproheptadine inhibited edema by 31 and 59%, respectively. The anti-allergic
      compounds ketotifen and azelastine, although effective against allergic
      inflammation in non-boosted mice, had a reduced or no effect in boosted mice. Our
      results suggest that allergic edema is less sensitive to antihistamine and anti
      allergic drugs in boosted mice, which may be accounted for by an increased role
      of other mediators.

PMID- 1358630
TI  - The inhibitory effect of opioid and alpha 2-adrenoceptor agonists on cardiac
      sensory neurones is pertussis toxin-insensitive.
AB  - The role of pertussis toxin-sensitive G proteins on the alpha 2-adrenoceptor and
      mu-opioid receptor-mediated inhibition of the efferent function of capsaicin
      sensitive neurones was investigated in guinea-pig atria pretreated with
      guanethidine. In the presence of atropine, CGP 20712A (2-hydroxy-5-(2-[hydroxy-3
      (4-[(1-methyl- 4-trifluormethyl)1H-imidazol-2-yl]-phenoxy)propyl]aminoethoxyl+
      ++)-benzamide) and prazosin, [D-Ala2,NMe-Phe4,Gly5-ol]enkephalin (DAGO, 0.1-3
      microM) and 2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo(4,5-d)azepine (BHT
      920, 0.01-1 microM) reduced the positive inotropic effect induced by transmural
      stimulation of preparations obtained from control and from pertussis toxin
      treated animals. These results suggest that pertussis toxin-sensitive G proteins
      are not involved in the inhibitory regulation of the efferent function of
      capsaicin-sensitive nerve terminals in cardiac tissue induced by alpha 2 and
      opioid receptor stimulation.

PMID- 1358631
TI  - Potentiation of 5-hydroxytryptamine-induced contraction in rat aorta by
      chlorpheniramine, citalopram and fluoxetine.
AB  - This study examined the effects of chlorpheniramine, citalopram and fluoxetine on
      5-hydroxytryptamine (5-HT)-induced contraction and 5-HT uptake in rat thoracic
      aortic rings in vitro. Chlorpheniramine and citalopram markedly potentiated 5-HT
      induced contraction. Potentiation by fluoxetine was less pronounced.
      Chlorpheniramine (0.01-1 microM) and citalopram (0.1-1 microM) induced
      concentration-dependent parallel shifts to the left of the 5-HT concentration
      response curves. The potentiation by chlorpheniramine was selective as
      chlorpheniramine (1 microM) did not potentiate phenylephrine-induced contraction.
      The potentiation did not depend upon the presence of endothelium, and was not
      related to H1 receptor antagonism as diphenhydramine and pyrilamine (1 microM)
      did not similarly enhance 5-HT-induced contractions. Whereas cocaine (1-10
      microM) similarly potentiated 5-HT-induced contraction, imipramine (1-10 microM)
      inhibited, rather than enhanced, contraction elicited by 5-HT. In the presence of
      10 microM cocaine, maximally effective concentrations of chlorpheniramine (1
      microM) or citalopram (100 nM) did not induce any additional potentiation of 5-HT
      induced contraction. Cooling (4 degrees C) markedly inhibited uptake of [3H]5-HT
      in rings with and without endothelium. Although less marked, imipramine (10
      microM), cocaine (1 microM), chlorpheniramine (1 microM) and citalopram (100 nM)
      inhibited [3H]5-HT uptake in endothelium-intact and endothelium-denuded rings.
      Fluoxetine also inhibited [3H]5-HT uptake, but the inhibition was only
      statistically significant in endothelium-intact rings. The monoamine oxidase
      (MAO) inhibitor, pargyline (10-100 microM), did not significantly affect 5-HT
      induced contraction. The results demonstrate that chlorpheniramine, citalopram
      and to a lesser extent, fluoxetine potentiate 5-HT-induced contraction in rat
      aorta in which neuronal 5-HT uptake is negligible. The data are consistent with
      inhibition of non-neuronal 5-HT uptake as at least one mechanism responsible for
      potentiation of 5-HT-induced contraction in rat aorta by chlorpheniramine,
      citalopram and fluoxetine.

PMID- 1358632
TI  - Ascending neural pathways in the rat ileum in vitro--effect of capsaicin and
      involvement of nitric oxide.
AB  - The aim of the present study was to develop and characterize an in vitro model of
      the rat ileum in which activation of the orally projecting neural excitatory
      pathway of the myenteric reflex is produced by electrical field stimulation
      anally to the recording site. The motility of a 10-cm segment of rat ileum was
      recorded using a perfused manometric assembly with side holes 2 and 4 cm orally
      to the stimulation site. Electrical field stimulation caused a contractile
      response in the oral but not in the aboral direction of the stimulation site. The
      contractile response, which was maximal using low stimulus frequencies (3 or 5
      pulses per second (pps)) and decreased with higher frequencies (10 or 20 pps),
      was blocked by atropine (10(-6) M) at all frequencies tested after acute and
      after prolonged (greater than 30 min) treatment. The maximal contractile response
      at 3 pps was abolished by hexamethonium (10(-4) M), tetrodotoxin (5 x 10(-7) M)
      and by complete transection of the muscular wall between the stimulation and the
      recording site. Acute administration of capsaicin (8 x 10(-7) M) to the bath
      reduced the lag between the start of the electrical stimulation and the onset of
      the contractile response. Higher concentrations of capsaicin (10(-5) M) reduced
      the contractile response, but this was partly due to an unspecific effect of
      capsaicin. Blockade of nitric oxide (NO) synthesis by L-NG-nitro-arginine-methyl
      ester (L-NAME) (3 x 10(-4) M) augmented the contractile response to anal
      stimulation by 222.4% and reduced the lag period by 54.5%, whereas the
      stereoisomer D-NAME had no significant effect. The potentiating effects of L-NAME
      were reversed in the presence of L-arginine (3 x 10(-3) M) but not in the
      presence of the stereoisomer D-arginine (3 x 10(-3) M). This model can be used to
      study ascending neural pathways in the rat small intestine. The ascending
      excitatory response is abolished by atropine and hexamethonium and is modulated
      by capsicin-sensitive fibers. The ascending pathway is under tonic inhibition of
      metabolites of the L-arginine-NO pathway.

PMID- 1358633
TI  - Calcitonin gene-related peptide is a venous dilator in conscious rats.
AB  - The effect of calcitonin gene-related peptide (CGRP) on body venous tone is not
      known. This study examines the dose-response effects of rat alpha CGRP on mean
      circulatory filling pressure (MCFP), an index of body venous tone, in conscious
      rats. Dose-response curves of CGRP were constructed in three groups of rats,
      namely, (I) intact, (III) rats pretreated with the ganglionic blocker
      hexamethonium and (V) rats pretreated with noradrenaline to raise mean arterial
      pressure (MAP) and MCFP. Three additional groups, (II), (IV) and (VI), served as
      time controls and were treated similarly to (I), (III) and (V), respectively,
      except that they were given saline (0.9% NaCl) in place of CGRP. The infusion of
      CGRP in intact rats dose dependently decreased MAP, increased heart rate (HR) and
      slightly reduced MCFP. In ganglionic-blocked rats, CGRP caused similar depressor
      responses but less tachycardia than in intact rats, however, it also slightly
      reduced MCFP. In rats given noradrenaline, CGRP dose dependently decreased MAP,
      MCFP and increased HR. The results show that CGRP has venodilator activities; its
      venous effect is best revealed at elevated venous tone.

PMID- 1358634
TI  - Partial dopamine D2 receptor agonists antagonize prolactin-regulating D2
      receptors in a transfected clonal cell line (GH4ZR7).
AB  - (-)-(3-Hydroxyphenyl)-N-n-propylpiperidine ((-)-3-PPP) and transdihydrolisuride
      (terguride, TDHL) are partial dopamine D2 receptor agonists displaying low
      intrinsic activity at normosensitive postsynaptic dopamine D2 receptors in brain
      while activating prolactin-regulating dopamine D2 receptors in male rats with an
      efficacy close to that of full dopamine D2 receptor agonists. In the present
      study we examined the effects of these partial dopamine D2 receptor agonists on
      prolactin release in vitro. For this purpose prolactin-producing tumour cells
      which have been transfected with the dopamine D2 receptor cDNA and hence which
      express a dopamine D2 receptor (short isoform) that is functionally active with
      respect to inhibition of adenylate cyclase and prolactin release (GH4ZR7; Albert
      et al., J. Biol. Chem. (1990) 265, 2098) were used. While the full dopamine D2
      receptor agonists, quinpirole, (+)-(3-hydroxyphenyl)-N-n-propylpiperidine ((+)-3
      PPP) and dopamine induced a dose-dependent suppression of vasoactive intestinal
      peptide (VIP)-induced prolactin release from GH4ZR7, both (-)-3-PPP and terguride
      were inactive. Furthermore, the prolactin-suppressive effects of dopamine and
      quinpirole were significantly antagonized by pretreatment with (-)-3-PPP and
      terguride. It is concluded that partial dopamine D2 receptor agonists, which
      activate male lactotroph dopamine D2 receptors in vivo, may antagonize dopamine
      D2 receptors on GH4ZR7 cells. There were similar results from an experiment using
      monolayers of anterior pituitary cells from male rats. Thus, in this in vitro
      preparation (+)-3-PPP suppressed spontaneous prolactin release while (-)-3-PPP
      again was inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358636
TI  - Response of monoaminergic and neuropeptide systems to 4-methylaminorex: a new
      stimulant of abuse.
AB  - 4-Methylaminorex is an amphetamine analog which has recently gained attention due
      to its potential as a stimulant of abuse and the ease with which it is
      synthesized. Administration of acute and multiple doses of 4-methylaminorex
      caused rapid (3-h) and long-term (7-day) declines in striatal tryptophan
      hydroxylase activity with few changes in other serotonergic parameters. The acute
      response by tryptophan hydroxylase to this drug was reversed by incubating the
      tissues in a reducing environment suggesting that 4-methylaminorex alters this
      enzyme through oxidative mechanisms. The 4-methylaminorex-induced long-term
      reduction in tryptophan hydroxylase activity might be due to neurotoxic action on
      serotonergic systems. In contrast, although a decline in striatal tyrosine
      hydroxylase occurred 3 h following a single dose of 4-methylaminorex, no changes
      in this enzyme were observed at 7 days after acute or multiple dosing with this
      drug. This result suggests that 4-methylaminorex is not neurotoxic to the
      dopaminergic neurons. Even though this amphetamine analog apparently does not
      have long-term effects on dopaminergic systems, it does appear to enhance
      substantially dopaminergic activity. Evidence for increased dopamine activity
      resulting from 4-methylaminorex administration included dramatic but temporary
      rises in the levels of nigral neurotensin, dynorphin A and substance P following
      multiple drug administration. Similar peptide changes have been observed with
      other amphetamine-related stimulants and are mediated by increases in
      dopaminergic activity. In summary, 4-methylaminorex has significant impact on
      monoaminergic pathways. In general, its spectrum of effects on these systems is
      like that of the ring-substituted amphetamines, such as
      methylenedioxymethamphetamine.

PMID- 1358635
TI  - Triazolam blocks the initial rotational effects of quinpirole but permits the
      later developing reduction of dopamine D2-mediated rotational behavior and
      dopamine D2 receptors.
AB  - Continuous infusion of the dopamine D2 receptor agonist quinpirole into mice with
      unilateral striatal 6-hydroxydopamine lesions initially produces a supersensitive
      rotational behavior. This is followed by reductions of dopamine D2-mediated
      behavior and dopamine D2 receptors. In this study we attempted to determine if it
      is possible to inhibit the acute increase in D2-mediated behavior while still
      allowing the reduction of D2-mediated behavioral responses and dopamine D2
      receptors to occur. Mice were implanted with Alzet minipumps containing either
      quinpirole alone or quinpirole combined with the GABA receptor modulator
      triazolam or the dopamine D2 receptor antagonist sulpiride, and rotational
      behavior was monitored for the 6 days of infusion. The pumps were then removed,
      and D2 receptors in striatal membranes were determined. Triazolam completely
      blocked the initial rotational behavior normally induced by implanting
      quinpirole. However, the quinpirole-induced reduction of D2-mediated behavioral
      responses and D2 receptors still occurred. Continuous infusion of sulpiride also
      inhibited the rotational behavior produced by quinpirole, but it prevented the
      reduction of dopamine D2 receptors. We conclude that up-regulated dopamine
      receptors and dopaminergic behaviors can be reversed by the continuous
      administration of a dopamine receptor agonist and that this reversal can occur
      without producing an initial exacerbation of dopaminergic responses. These
      results suggest that this type of treatment regimen might be useful for treating
      clinical conditions associated with dopaminergic supersensitivity.

PMID- 1358637
TI  - Behavioural studies on WAY100289, a novel 5-HT3 receptor antagonist, in two
      animal models of anxiety.
AB  - The novel 5-HT3 receptor antagonist, WAY100289, was examined in two animal models
      of anxiety: the mouse two-compartment light: dark box, and the rat potentiated
      acoustic startle paradigm. The activity of WAY100289 in the light: dark box model
      was also compared with that of the selective 5-HT3 receptor antagonists
      ondansetron, zacopride, ICS-205,930 and quaternary ICS-205,930 (QICS). WAY100289
      mimicked the activity profile of benzodiazepine positive controls in the mouse
      light: dark box, i.e. WAY100289 markedly and significantly increased the
      exploratory activity of mice in the more aversive light compartment, at doses of
      0.01-1.0 mg/kg s.c. and 0.1-10.0 mg/kg p.o. Zacopride and ondansetron induced
      comparable effects at doses of 0.001-1.0 mg/kg s.c. ICS-205,930 displayed a
      markedly biphasic dose-response relationship; being active at 0.01 mg/kg s.c.,
      but not at higher or lower doses. QICS was not active in the light: dark box up
      to a dose of 10 mg/kg s.c., suggesting that the compound does not enter the brain
      readily. WAY100289 was also active in the rat potentiated acoustic startle model,
      significantly attenuating the potentiated startle response at doses of 0.03 and
      0.3 mg/kg s.c. The activity profile of WAY100289 in this model resembled that of
      ondansetron. These data strongly suggest that WAY100289 may possess anxiolytic
      properties in the clinic.

PMID- 1358638
TI  - GABAB receptor activation partially inhibits N-methyl-D-aspartate-mediated
      tyrosine hydroxylase stimulation in rat striatal slices.
AB  - The effect of the GABAB agonist, (+/-)-baclofen, on the N-methyl-D-aspartate
      (NMDA)-mediated stimulation of tyrosine hydroxylase activity was investigated in
      slices of rat striatum. Tyrosine hydroxylase activity was stimulated by NMDA in a
      concentration-dependent manner (EC50, 1.3 +/- 0.3 microM; maximum stimulation 194
      +/- 7% of basal activity). The action of NMDA was reversed by the NMDA
      antagonist, 2-amino-5-phosphonovalerate (AP-5). (+/-)-Baclofen (100 microM)
      decreased the maximum effect of NMDA by 24 +/- 2% without significantly modifying
      its EC50. The IC50 for the inhibitory action of (+/-)-baclofen was 4.2 +/- 1.2
      microM. These results show that GABAB receptor activation modulates NMDA
      stimulated tyrosine hydroxylase activity, further supporting the possibility of a
      role of GABA in the regulation of striatal dopaminergic neurotransmission.

PMID- 1358639
TI  - Antidepressant profile in rodents of SR 58611A, a new selective agonist for
      atypical beta-adrenoceptors.
AB  - beta 2-Adrenoceptor agonists possess antidepressant-like activity in animals and
      man, but their peripheral side-effects prevent their therapeutic use. Atypical
      beta-adrenoceptors have not been demonstrated in the central nervous system, but
      are known to exist in peripheral tissues such as the rat colon. We have now
      studied the antidepressant-like effects in rodents of a new selective atypical
      beta-adrenoceptor agonist, SR 58611A. SR 58611A was active with minimal effective
      doses of 0.1-0.3 mg kg-1 i.p. in several models (antagonism of the hypothermia
      induced by apomorphine and reserpine; potentiation of the toxicity produced by
      yohimbine; reversal of learned helplessness), but was inactive in the tests of
      reserpine-induced ptosis and behavioural despair. The antidepressant-like effect
      of SR 58611A was not antagonised by selective beta 1- or beta 2-adrenoceptor
      antagonists, but was blocked by high doses of the non-selective beta-adrenoceptor
      antagonists, propranolol and alprenolol. Unlike beta 2-adrenoceptor agonists, SR
      58611A did not reduce locomotor activity or increase water intake at doses up to
      10 mg kg-1. Therefore, SR 58611A may represent the prototype of a new class of
      antidepressant compounds.

PMID- 1358640
TI  - Are the prejunctional alpha 2-adrenoceptors of the rat vas deferens and
      submandibular gland of the alpha 2A- or alpha 2D-subtype?
AB  - We have investigated the effects of antagonists at functional prejunctional alpha
      2-adrenoceptors of rat was deferens and rat submandibular gland and compared
      potencies with affinities for the alpha 2A-, alpha 2B- and putative alpha 2D
      ligand binding sites of human platelet, rat kidney, and rat submandibular gland,
      respectively. Prejunctional potency of antagonists was expressed as an EC30
      (concentration producing a 30% increase in stimulation-evoked release of tritium
      in tissues pre-incubated with [3H]noradrenaline) in rat vas deferens and
      submandibular gland, and also as a pA2 (antagonist concentration producing a 2
      fold shift in the inhibition by the alpha 2-adrenoceptor agonist xylazine of the
      electrically-evoked isometric twitch) in rat vas deferens. The functional
      prejunctional alpha 2-adrenoceptors of rat vas deferens and submandibular gland
      are alpha 2A-like since there was a good correlation between affinity for the
      alpha 2A-ligand binding site in human platelet and prejunctional potency in rat
      vas deferens (r = 0.90, n = 7, P less than 0.001), and submandibular gland (r =
      0.84, n = 7, P less than 0.05). However, there was a better correlation between
      affinity for the alpha 2-ligand binding site of rat submandibular gland and
      prejunctional potency in rat vas deferens (r = 0.95, n = 7, P less than 0.001),
      and submandibular gland (r = 0.97, n = 7, P less than 0.001).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1358641
TI  - The intrathecal administration of excitatory amino acid receptor antagonists
      selectively attenuated carrageenan-induced behavioral hyperalgesia in rats.
AB  - A single unilateral injection of carrageenan (4.5-6.0 mg in 0.15-0.20 ml saline)
      into the rat hindpaw induced behavioral hyperalgesia as evidenced by a
      significant reduction in hindpaw withdrawal latency to a noxious thermal
      stimulus. The involvement of N-methyl-D-aspartate (NMDA) receptors in this model
      of hyperalgesia was examined by intrathecal administration of the selective
      excitatory amino acid (EAA) receptor antagonists: (+/-)-2-amino-5
      phosphonopentanoic acid (AP-5), (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1
      phosphonic acid (CPP), ketamine hydrochloride (ketamine), 7-chlorokynurenic acid
      (7-Cl kynurenic acid), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The
      effects of dizocilpine maleate (MK-801) were studied under the same conditions
      and published previously (Ren et al., 1992) and the data are presented for
      comparison. While the withdrawal latencies of the non-injected paws and of the
      paws of naive rats were not significantly affected by application of the EAA
      receptor antagonists at doses tested, the paw withdrawal latencies of the
      carrageenan-injected paws were elevated dose dependently. The rank order of
      potency of these agents to reduce hyperalgesia was: MK-801 greater than or equal
      to AP-5 greater than or equal to CPP = 7-Cl kynurenic acid = ketamine much
      greater than CNQX greater than 0. In contrast, intrathecal injection of the
      opioid receptor agonists, [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO, mu-selective)
      and [D-Pen2,D-Pen5] enkephalin (DPDPE, delta-selective), produced antinociception
      in both injected and non-injected paws. DAMGO was much more potent, while DPDPE
      was less potent, than MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358642
TI  - Bifemelane enhances high K(+)-evoked release of glutamate from mossy fiber
      synaptosomes of guinea-pig hippocampus.
AB  - We have shown that bifemelane augments long-term potentiation in the mossy fiber
      CA3 system, but not in the Schaffer collateral-CA1 system. To elucidate the
      mechanism of action of bifemelane in relation to pathway-specific augmentation of
      long-term potentiation, we prepared a mossy fiber terminal-rich synaptosomal
      fraction (P3) from guinea-pig hippocampus and investigated the effect of
      bifemelane on the release of glutamate from these synaptosomes, using an in vitro
      superfusion technique. Bifemelane (0.01-1 microM) dose dependently increased the
      30 mM K(+)-evoked release of glutamate from the P3 fraction, without affecting
      glutamate release from a conventional synaptosomal P2 fraction. This stimulatory
      effect of 1 microM bifemelane was abolished by 100 microM H-7, which also
      suppressed the increase in K(+)-evoked glutamate release by phorbol 12,13
      dibutyrate (1 microM). Bifemelane (1 microM) induced the translocation of protein
      kinase C activity from cytosol to membrane in the P3 fraction (which contains
      large and irregular-shaped synaptosomes probably derived from mossy fiber
      terminals), but not in the P2 fraction. These findings suggest that bifemelane
      directly acts on mossy fiber terminals to potentiate depolarization-induced
      glutamate release, which may be at least partly mediated by the translocation
      (activation) of protein kinase C.

PMID- 1358643
TI  - Lesions of the mesotelencephalic dopamine system enhance the effects of selective
      dopamine D1 and D2 receptor agonists on striatal acetylcholine release.
AB  - In vivo microdialysis was used to determine the effects of 6-hydroxydopamine (6
      OHDA) lesions of the mesotelencephalic dopamine system on dopamine receptor
      agonist induced changes in extracellular acetylcholine (ACh) concentrations in
      the striatum. Such lesions increased the inhibitory effect of a low dose of the
      D2 receptor agonist quinpirole (0.05 mg/kg s.c.) on striatal ACh release. In
      addition, 6-OHDA lesions enhanced the facilitatory effect of the selective D1
      receptor agonist CY 208-243 on striatal ACh release, enabling a subthreshold (0.2
      mg/kg s.c.) dose to increase striatal dialysate concentrations of ACh by over
      60%. These results indicate that denervation supersensitivity potentiates both
      the facilitatory effects of D1 receptor agonists and the inhibitory effects of D2
      receptor agonists on striatal cholinergic activity. It was also found that the 6
      OHDA lesions reduced basal interstitial ACh concentrations by 75% in the
      ipsilateral striatum. The later results are consistent with the hypothesis that
      the prepotent action of dopamine in the forebrain is to enhance striatal ACh
      release via a D1 receptor mechanism.

PMID- 1358644
TI  - Role of Ca2+ channel blockers in insulin secretion resulting from alpha 1- and
      beta-adrenoceptor stimulation in the rabbit.
AB  - In conscious fasted rabbits the i.v. infusion of amidephrine (alpha 1-agonist) or
      isoprenaline (beta-agonist) induced an increase in plasma levels of
      immunoreactive insulin. The alpha 1-mediated response was suppressed in animals
      pretreated with calcium channel blockers (verapamil and elgodipine). The
      potentiated insulin secretory response in rabbits exposed to dual (alpha 1 +
      beta) adrenoceptor stimulation was also prevented by verapamil and elgodipine.
      These results suggest that extracellular calcium is required to mediate the
      effects of amidephrine on insulin secretion and to support potentiation.

PMID- 1358646
TI  - Ethanol inhibits release of excitatory amino acids from slices of hippocampal
      area CA1.
AB  - Slices of hippocampal area CA1 were employed to test the hypothesis that release
      of excitatory amino acids glutamate and aspartate is regulated by ethanol. K(+)
      evoked release of glutamate and aspartate was inhibited by ethanol (25-100 mM) in
      a dose-dependent manner. Ethanol (100 mM) also inhibited K(+)-evoked gamma
      aminobutyric acid release. This selective inhibition of excitatory amino acid
      release by ethanol may contribute to some of the learning and memory deficits
      associated with ethanol abuse, since excitatory amino acid receptors play an
      important role in synaptic plasticity processes.

PMID- 1358645
TI  - The effect of intrathecally administered imiloxan and WB4101: possible role of
      alpha 2-adrenoceptor subtypes in the spinal cord.
AB  - To define the antagonist pharmacology of spinal antinociceptive effects of alpha
      2-adrenoceptor agonists, the ability of WB4101 (2-(2,6-dimethoxyphenoxyethyl)
      aminomethyl-1,4-benzodioxane) and imiloxan to antagonize the effect of spinal ST
      91 (2-[2,6-diethylphenylamino]-2-imidazoline), clonidine and dexmedetomidine was
      examined. Antinociceptive effects of ST-91 were antagonized by WB4101 and
      imiloxan; clonidine only by WB4101; and, dexmedetomidine was not antagonized by
      either antagonist. It is hypothesized that the alpha 2 adrenoceptor subtype alpha
      2A is involved in the antinociception of spinal clonidine and dexmedetomidine,
      and alpha 2B is involved in that of ST-91.

PMID- 1358647
TI  - Effect of excitatory amino acid receptor antagonists on apomorphine-, oxytocin-
      and ACTH-induced penile erection and yawning in male rats.
AB  - The effect of excitatory amino acid receptor antagonists, (5R,10S)-(+)-5-methyl
      10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5, 10-imine hydrogen maleate ((+)-MK
      801), (+/-)-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid (CPP), 6-cyano
      7-nitroquinoxaline-2,3-dione (CNQX) and (+/-)-2-amino-4-phosphonobutanoic acid
      (AP-4), on penile erection and yawning induced by subcutaneous apomorphine (80
      micrograms/kg), intracerebroventricular (i.c.v.) oxytocin (30 ng) and
      adrenocorticotropin (ACTH)-(1-24) (10 micrograms) was studied in male rats.
      Intraperitoneal (0.1-0.4 mg/kg) and i.c.v. (10-50 micrograms) (+)-MK-801
      prevented dose dependently the penile erection and yawning induced by the three
      drugs. The (+)-MK-801 effect coincided with the appearance of head weaving, body
      rolling, hyperlocomotion and ataxia. Haloperidol (0.5 mg/kg i.p.) antagonized the
      prevention by (+)-MK-801 of oxytocin responses. Penile erection but not yawning
      was also prevented by high, but not low doses of CPP and CNQX, which impaired
      motor performance, AP-4 was ineffective at all doses tested. The above compounds
      were ineffective when injected into the paraventricular nucleus of the
      hypothalamus, the brain area where apomorphine and oxytocin act to induce penile
      erection and yawning. The results suggest that excitatory amino acid transmission
      is not involved in the expression of penile erection and yawning induced by the
      above compounds.

PMID- 1358648
TI  - Effects of tertatolol, a beta-adrenoceptor antagonist with agonist affinity at 5
      HT1A receptors, in an animal model of migraine: comparison with propranolol and
      pindolol.
AB  - Constriction of carotid arteriovenous anastomoses is a common property of several
      antimigraine drugs. The present study concerns the effects of tertatolol (0.1,
      0.3, 1 and 3 mg/kg i.v.), a novel beta-adrenoceptor antagonist with an agonist
      action on 5-HT1A receptors, on systemic haemodynamics and carotid blood flow
      distribution in the anaesthetized pig. Two other beta-adrenoceptor antagonists,
      one (propranolol) with and one (pindolol) without antimigraine actions, were
      compared (doses: 0.03, 0.1, 0.3 and 1 mg/kg i.v.) with tertatolol in this animal
      experimental model of migraine. While the beta-adrenoceptor antagonist with
      partial agonist action, pindolol, increased heart rate and cardiac output,
      propranolol and tertatolol decreased these variables moderately. Mean arterial
      blood pressure also decreased with the two highest doses of propranolol and with
      the highest dose of tertatolol. The calculated total peripheral conductance
      decreased with the first three doses of tertatolol. Carotid haemodynamic
      variables were not affected by pindolol, except for some increase in the nutrient
      fraction after the highest dose. Propranolol and especially tertatolol decreased
      both total carotid blood flow and arteriovenous anastomotic blood flow without
      affecting the nutrient fraction. In the case of tertatolol, blood flow decreases
      were accompanied by similar decreases in vascular conductance, indicating active
      arteriovenous anastomotic constriction. It is therefore suggested that tertatolol
      may prove effective in the treatment of migraine.

PMID- 1358649
TI  - Role of acetylcholinesterase in airway epithelium-mediated inhibition of
      acetylcholine-induced contraction of guinea-pig isolated trachea.
AB  - To seek evidence for the involvement of acetylcholinesterase activity in the
      modulatory influence of the airway epithelium, we examined responses to
      acetylcholine (ACh), bethanechol, histamine or KCl in isolated epithelium-intact
      and epithelium-denuded guinea-pig trachealis preparations. The concentration
      response curves to ACh were shifted 26-fold to the left by epithelial denudation
      but the contractile response to KCl was not altered. The response to histamine in
      epithelium-denuded preparations increased 4-fold with no attenuation in the
      presence of physostigmine (30 nM). Physostigmine (30 nM) potentiated the response
      to ACh in epithelium-intact tissues more (about 26-fold) than in epithelium
      denuded tissues (about 3.5-fold). Thus, in the presence of physostigmine removing
      the epithelium had only a slight effect (not statistically significant) on the
      potency of ACh to contract the trachea. Removing the epithelium had no effect on
      the potency of bethanechol, a muscarinic receptor agonist that is not a substrate
      for cholinesterases. Physostigmine itself contracted the trachealis muscle but
      the pD2 values and maximum responses in epithelium-intact and denuded
      preparations were not significantly different. The frequency-response curves to
      electrical field-stimulated cholinergic contractions were unaffected by removing
      the epithelium. In conclusion, the principal mechanism by which the epithelium
      inhibits contraction of guinea-pig trachea to exogenously applied ACh is via
      epithelium-derived acetylcholinesterase activity.

PMID- 1358650
TI  - Effects of inhaled alpha 2-adrenoceptor and GABAB receptor agonists on citric
      acid-induced cough and tidal volume changes in guinea pigs.
AB  - The effects of alpha 2-adrenoceptor and GABA receptor agonists on citric acid
      induced cough and increased tidal volume were investigated in conscious guinea
      pigs. Inhalation of low doses of B-HT 920 (5-allyl-2-amino 5,6,7,8-tetrahydro-4H
      thiazolo[4,5-d]azepine dihydrochloride), and xylazine significantly inhibited
      citric acid-induced cough and tidal volume increases. Intraperitoneal
      administration of higher doses of B-HT 920 than those given by aerosol were
      ineffective. The inhibitory effects of B-HT 920 were antagonised by prior
      intraperitoneal administration of yohimbine, but not atropine. Inhalation of GABA
      or baclofen inhibited tidal volume increases, but had no effect on cough. Inhaled
      alpha 2-adrenoceptor or GABA agonists had no effect on the reduced respiratory
      rate after citric acid inhalation. It is concluded that alpha 2-adrenoceptor
      agonists inhibit cough via a mechanism which may not be related to their ability
      to reduce citric acid-induced tidal volume increases, since GABA and baclofen
      inhibited tidal volume increases but not cough. We suggest that alpha 2
      adrenoceptor agonists may have therapeutic potential in the treatment of cough.

PMID- 1358651
TI  - 5-HT2/5-HT1C receptor-mediated facilitatory action on unit activity of ventral
      horn cells in rat spinal cord slices.
AB  - 5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) and 1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane (DOI) facilitate motoneuron excitability through 5-HT1C/5-HT2
      receptors in rats. Using spinal cord slices prepared from adult rats, we recorded
      unitary cell discharges, evoked by local stimulation of the adjacent site,
      extracellularly in the motor nuclei of the ventral horn. 5-MeODMT, DOI, 5
      hydroxytryptamine (5-HT), 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) and
      tandospirone facilitated the probability of firing in the motor nuclei, with 5
      MeODMT and DOI being the most potent. The effect of 5-MeODMT was significantly
      suppressed by ketanserin (a 5-HT2 receptor-selective antagonist), spiperone (a 5
      HT1A/5-HT2 receptor antagonist) and cyproheptadine (a 5-HT1C/5-HT2 receptor
      antagonist), but not by 3-tropanyl-3,5-dichlorobenzoate (MDL 72222, a 5-HT3
      receptor-selective antagonist) or pindolol (a 5-HT1A/5-HT1B receptor antagonist).
      This suggests that 5-HT2 and/or 5-HT1C receptors are involved in the facilitatory
      effects of 5-HT receptor agonists on the synaptic activity of ventral horn cells.

PMID- 1358652
TI  - Antidiabetic sulfonylureas antagonize somatostatin inhibition of prolactin
      secretion in vitro.
AB  - Somatostatin-induced inhibition of prolactin secretion from adenohypophysis cells
      in culture is antagonized by the sulfonylurea glipizide, a specific blocker of
      ATP-sensitive K+ channels. The affinity constant for glipizide is K0.5 = 10 +/- 5
      nM.

PMID- 1358653
TI  - Suppression by dynorphin A-(1-13) of the expression of opiate withdrawal and
      tolerance in mice.
AB  - Dynorphin A-(1-13) has been shown to suppress the expression of opiate withdrawal
      and tolerance dose dependently in morphine-dependent mice when administered i.v.
      The ED50 of naloxone to precipitate withdrawal jumping was increased by 1.5- and
      7-fold when morphine-dependent mice were pretreated with 2.5 and 5.0 mumol/kg of
      dynorphin A-(1-13), respectively. When dynorphin A-(1-13) (5.0 mumol/kg, i.v.)
      was administered after the precipitation of withdrawal with naloxone, the ED50 of
      naloxone was still increased by over 2-fold. Also, the expression of tolerance
      which was estimated by noting the antinociceptive ED50 of morphine, was inhibited
      by over 70% with a dynorphin A-(1-13) dose of 2.5 mumol/kg and completely
      suppressed by pretreatment with 5.0 mumol/kg of dynorphin A-(1-13) i.v. The
      mechanism by which dynorphin A-(1-13) produces these effects when given i.v.
      remains to be elucidated.

PMID- 1358654
TI  - Long-term alteration in the central monoaminergic systems of the rat by 2,4,5
      trihydroxyamphetamine but not by 2-hydroxy-4,5-methylenedioxymethamphetamine or 2
      hydroxy-4,5-methylenedioxyamphetamine.
AB  - The long-term effects of three metabolites of 3,4-methylenedioxymethamphetamine
      (MDMA) on the central monoaminergic systems of the rat were examined. Seven days
      after the intracerebroventricular administration of 0.25 and 0.5 mumol 2,4,5
      trihydroxyamphetamine, hippocampal tryptophan hydroxylase (TPH) activity was
      reduced to 5 and 1% of control, respectively, while norepinephrine (NE)
      concentration was depressed to 10 and 18% of control. These two respective
      dosages also decreased striatal tyrosine hydroxylase (TH) activity to 67 and 10%
      of control, respectively, while nigral TH activity was reduced to 59 and 20% of
      control. Striatal TPH activity was reduced to 74 and 81% of control,
      respectively, while the activity in the dorsal and median raphe remained
      unaltered. The intracerebroventricular administration of 1 mumol 2-hydroxy-4,5
      methylenedioxymethamphetamine (6-OH-MDMA) failed to alter TPH activity, TH
      activity or NE concentration after 14 days. In contrast, 1 mumol of 2-hydroxy-4,5
      methylenedioxyamphetamine (6-OH-MDA) induced a 30% increase in striatal TPH
      activity and a 50% increase in nigral TH activity. The study of the formation of
      2,4,5-trihydroxyamphetamine after MDMA treatment may provide insight as to how
      MDMA destroys serotonergic nerve terminals.

PMID- 1358655
TI  - Effects of tandospirone in three behavioral tests for anxiolytics.
AB  - The azapirone putative anxiolytic tandospirone was evaluated in two behavioral
      screening methods that identify known azapirone anxiolytics and one method that
      identifies only sedative-hypnotic anxiolytics. Tandospirone produced a large
      increase in punished key-pecking for food in pigeon and a large increase in cork
      gnawing in rat. It did not produce a large increase in punished lever-pressing
      for food in rat, a result that to some extent contradicts reports from other
      laboratories. It was equipotent with buspirone in pigeon, but in rat it was ten
      times less potent than buspirone in disrupting the lever-press response and
      increasing cork gnawing. The results indicate that tandospirone is qualitatively
      similar to the other azapirone anxiolytics buspirone, gepirone and ipsapirone and
      is different from sedative-hypnotic anxiolytics.

PMID- 1358656
TI  - Continuous alpha 2-adrenoceptor blockade by atipamezole decreases neocortical
      high-voltage spindle activity in rats.
AB  - The present study investigates the effects of a subchronic continuous infusion of
      atipamezole, a potent and selective alpha 2-adrenoceptor antagonist, on
      neocortical high-voltage spindle (HVS) activity in rats. Six days' subcutaneous
      infusion of atipamezole (0.125 mg/kg per h) with osmotic minipumps decreased HVS
      activity significantly. The HVS activity-decreasing effect of atipamezole
      persisted at the same level throughout the infusion. A single subthreshold dose
      of an alpha 2-adrenoceptor agonist, guanfacine (0.001 mg/kg i.p.), did not affect
      HVS activity either before or after the continuous atipamezole treatment. The
      central alpha 2-adrenoceptor blocking effect of atipamezole (0.1 mg/kg per h
      s.c.) was confirmed to be at the same level after one, three or seven days'
      infusion, as assessed by measuring the antagonism of detomidine-induced mydriasis
      in the rat. The serum concentration of atipamezole (0.1 mg/kg per h s.c.)
      increased slightly from day 3 (37 +/- 11 ng/ml) to day 7 (45 +/- 4 ng/ml). In
      conclusion, the results of the study suggest that the suppressant effects of
      atipamezole on neocortical high-voltage spindle activity are preserved during
      subchronic continuous treatment. In addition, alpha 2-adrenoceptor blockade, as
      measured in the rat mydriasis model, persists at the same level during subchronic
      infusion.

PMID- 1358657
TI  - Amitriptyline inhibits striatal efflux of neurotransmitters via blockade of
      voltage-dependent Na+ channels.
AB  - Amitriptyline, a tricyclic antidepressant, almost completely inhibited
      veratridine- or scorpion toxin-evoked efflux of endogenous dopamine (DA) and
      gamma-aminobutyric acid (GABA) from rat striatal slices without any effects of 30
      mM K+ or 4-aminopyridine on basal and evoked efflux. The effects of amitriptyline
      on glutamate efflux were comparable to those on DA or GABA efflux. These effects
      of amitriptyline can be well explained by its blockade of voltage-dependent Na+
      channels and may be independent of other activities of this drug such as re
      uptake inhibition of monoamines and blockade of K+ channels.

PMID- 1358658
TI  - Protein kinase C phosphorylates a 15 kDa protein but not phospholamban in intact
      rat cardiac myocytes.
AB  - In the present study the effects of the protein kinase C activator 12-O
      tetradecanoylphorbol 13-acetate (TPA) as well as the alpha- and beta-adrenoceptor
      agonists methoxamine and isoproterenol on protein phosphorylation of intact rat
      cardiac myocytes were investigated. TPA, isoproterenol and methoxamine were shown
      to stimulate phosphorylation of a 15 kDa protein. EC50 for TPA and isoproterenol
      were 4 x 10(-8) M and 5 x 10(-9) M respectively. The time course of
      phosphorylation by TPA and isoproterenol greatly differed, revealing a maximal
      phosphorylation (2.9-fold) after 10 min and 1 min respectively. Cell
      fractionation showed a significant enrichment of the 15 kDa protein in a crude
      membrane preparation. While the 15 kDa protein was the only phosphoprotein
      stimulated by TPA and methoxamine, isoproterenol additionally enhanced the 32Pi
      incorporation into four proteins corresponding to 6 kDa (phospholamban), 28 kDa,
      97 kDa and 140 kDa. Furthermore, dephosphorylation of a 21 kDa substrate upon
      beta-adrenoceptor stimulation was observed. Phospholamban phosphorylation was
      effectively (max. 9.1-fold) stimulated by isoproterenol (EC50 of 5 x 10(-9) M),
      reaching a maximal phosphorylation state within 1 min. The present study clearly
      demonstrates: (1) TPA stimulates the phosphorylation of a membrane-localized 15
      kDa protein and this effect can be mimicked by both isoproterenol and
      methoxamine; (2) TPA, in contrast to isoproterenol, does not change the
      phosphorylation state of phospholamban. Whilst phospholamban under in vitro
      conditions is known to be a substrate for protein kinase C, it does not appear to
      be accessible for the enzyme in intact cardiac myocytes.

PMID- 1358659
TI  - Conantokin-G selectively inhibits N-methyl-D-aspartate-induced currents in
      Xenopus oocytes injected with mouse brain mRNA.
AB  - The conantokins are a family of peptides isolated from the venom of predatory
      marine snails of the genus Conus. Here we demonstrate that one of these peptides,
      conantokin-G, specifically inhibits the N-methyl-D-aspartate (NMDA) subtype of
      glutamate receptors that are expressed in mouse brain mRNA-injected Xenopus
      oocytes. Increasing the concentration of conantokin-G causes the NMDA dose
      response curve to shift to progressively higher concentrations. We therefore
      conclude that conantokin-G interacts with the glutamate binding site of the
      receptor. In contrast, the peptide does not compete with glycine, and this
      indicates that conantokin-G does not act at the binding site of this co-agonist
      of the NMDA receptor. Furthermore, the inhibitory effects of conantokin-G appear
      to be insensitive to membrane potential.

PMID- 1358660
TI  - Metabotropic receptor mediated afterdepolarization in neocortical neurons.
AB  - In rat neocortical slices activation of glutamate metabotropic receptors with
      glutamate, quisqualate and 1S,3R-ACPD caused a spike-evoked afterdepolarization
      which replaced the normal afterhyperpolarization. In some neocortical neurons the
      afterdepolarization reached action potential threshold causing prolonged self
      sustained firing. These effects of metabotropic receptor activation were similar
      to the action of muscarinic agonists in the same preparation.

PMID- 1358661
TI  - Interaction among mu-opioid receptors and alpha 2-adrenoceptors on SH-SY5Y human
      neuroblastoma cells.
AB  - The clonal human neuroblastoma cell line SK-N-SH-SY5Y was previously shown to
      express mu-opioid and alpha 2-adrenoceptors which are both negatively coupled to
      adenylyl cyclase. Because of the potential use of alpha 2-agonists in the
      treatment of narcotic dependence, we tested the interactions among he alpha 2
      agonists, clonidine and norepinephrine, and morphine on AC in SH-SY5Y cells.
      Pretreatment with retinoic acid resulting in partial neuronal differentiation
      greatly enhanced the cells' sensitivity towards adenylyl cyclase stimulation by
      prostaglandin E1, and its inhibition by morphine and alpha 2-agonists.
      Norepinephrine (EC50 = 69 nM) maximally inhibited prostaglandin E1-stimulated
      cAMP accumulation (by approximately 83%), and the alpha 2-agonist yohimbine
      reversed these effects. Clonidine (EC50 = 32 nM) was a partial agonist, with 50
      to 60% maximal inhibition. The combined effects of morphine (maximum
      approximately 70% inhibition) and norepinephrine exceeded the effect of either
      agent alone, yielding more than 90% inhibition of prostaglandin E1-stimulated
      cAMP accumulation. As previously reported for morphine, only a partial tolerance
      was observed for adenylyl cyclase inhibition by norepinephrine. Further, no cross
      tolerance was observed between clonidine and morphine. The combined results
      indicate that mu-opioid receptors and an alpha 2-adrenoceptor subtype are
      colocalized on the same cells in SH-SY5Y culture, which hence serves as a model
      to study opioid-alpha 2-adrenergic interactions.

PMID- 1358662
TI  - The cloned dopamine D2 receptor reveals different densities for dopamine receptor
      antagonist ligands. Implications for human brain positron emission tomography.
AB  - Since [3H]emonapride ([3H]YM-09151-2), a benzamide neuroleptic, consistently
      detects more dopamine D2 receptors than [3H]spiperone in the same tissue, we
      tested whether this property was inherent in the cloned dopamine D2 receptor. We
      found that the density of dopamine D2 receptors labelled by [3H]emonapride was
      1.5-fold to 2-fold (mean of 1.8-fold) higher than the density of dopamine D2
      receptors labelled by [3H]spiperone in cells expressing cloned dopamine D2
      receptors (either the short form (from rat) or the long form (from human)),
      matching similar findings in anterior pituitary tissue (rat or pig) or in post
      mortem human caudate nucleus tissue. The situation was similar for another
      benzamide, [3H]raclopride, which revealed 1.3-fold to 1.8-fold (mean of 1.5-fold)
      more binding sites than that for [3H]spiperone in cell membranes containing
      cloned dopamine D2 receptors. The apparently different dopamine D2 receptor
      densities revealed by these two types of 3H-ligands (i.e. [3H]spiperone and the
      [3H]benzamides), therefore, arise from an inherent property of the dopamine D2
      receptor protein. These findings for the cloned dopamine D2 receptor, therefore,
      partly explain the higher dopamine D2 receptor density measured in human brain
      (by positron emission tomography) when using radioactive raclopride compared to
      results using radioactive methylspiperone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358663
TI  - Site-directed mutagenesis of the human dopamine D2 receptor.
AB  - Based on amino acid sequence and computer modeling, two conflicting three
      dimensional models of the dopamine D2 receptor have been proposed. One model
      (Dahl et al., 1991, Proc. Natl. Acad. Sci. USA 88, 8111) suggests that dopamine
      interacts with aspartate 80 of transmembrane (TM) 2 and asparagine 390 of TM6
      with the transmembranes arranged in a clockwise manner, while a second model
      (Hibert et al., 1991, Mol. Pharmacol. 40, 8) suggests that dopamine interacts
      with aspartate 114 of TM3 and the serines of TM5 (194 and 197) with the
      transmembranes arranged in a counterclockwise manner when viewed from the
      extracellular space. The present study tests the latter model by selectively
      mutating aspartate 114 and serines 194 and 197 of the human dopamine D2 receptor
      by site-directed mutagenesis. In addition, two methionines (116 and 117) were
      mutated to evaluate whether residues near aspartate (114) of the dopamine D2
      receptor are critical in differentiating dopamine receptor agonists from
      adrenoceptor agonists. Removal of the negative charge with the mutation of
      aspartate (114) to either asparagine or glycine led to a total loss of both
      agonist and antagonist binding. Individual or dual methionine mutations in
      positions 116 and 117, to make the dopamine D2 binding pocket more closely
      resemble the beta 2-adrenoceptor, did not result in a change in selectivity
      toward noradrenergic agonists or antagonists. The serine mutations revealed
      interesting differences between the dopamine D2 receptor and the adrenoceptors.
      In particular, serine 197 appeared more important than serine 194 for agonist
      binding. In addition, the binding of one agonist (N-0437) was unaffected by
      individual serine mutations, while the binding of some antagonists, such as
      raclopride and spiperone, was significantly altered. These findings are discussed
      in relation to ligand structure and their interactions with the putative binding
      pocket.

PMID- 1358664
TI  - Formycin triphosphate as a probe for the ATP binding site involved in the
      activation of guanylate cyclase.
AB  - Formycin A triphosphate (FTP), a fluorescent analog of ATP, slightly increased
      basal guanylate cyclase activity, but significantly potentiated guanylate cyclase
      activity stimulated by atrial natriuretic factor (ANF) in rat lung membranes. FTP
      potentiated ANF-stimulated guanylate cyclase activity with an EC50 at about 90
      microM and inhibited ATP-stimulated guanylate cyclase activity with an IC50 at
      about 100 microM. These results indicate that FTP binds more tightly than ATP for
      the same binding site. Therefore, FTP would be an excellent tool for studying the
      ATP binding site.

PMID- 1358665
TI  - Thy-1 inhibits mitogen-induced Ca2+ oscillation in ras-transformed mouse
      fibroblasts.
AB  - Cell surface glycoprotein Thy-1 functions as a transformation suppressor in v-ras
      transformed NIH/3T3 cells [Sugimoto et al., (1991) Cancer Res. 51, 99-104.]. In
      order to understand the mechanism of action of Thy-1, we examined the effect of
      Thy-1 expression on mitogen-induced Ca2+ oscillation which was correlated with v
      ras-transformation [Fu et al., (1991) FEBS Lett. 281, 263-266.]. Forced
      expression of Thy-1 in v-ras-transformed cells inhibited mitogen-induced Ca2+
      oscillation. Although v-Ras-free, Thy-1-positive NIH/3T3 cells (major population)
      did not show Ca2+ oscillation, whereas in Thy-1-negative NIH/3T3 cells (less than
      1% of the population) Ca2+ oscillation was observed. Finally, replacement of the
      carboxyl-half of Thy-1 with that of CD4 abolished the inhibitory effect of Thy-1.
      These results suggest that Thy-1 directly or indirectly participates in the
      negative regulation of Ca2+ response by inhibiting Ca2+ oscillation.

PMID- 1358666
TI  - Experimental autoimmune anterior uveitis (EAAU). II. Dose-dependent induction and
      adoptive transfer using a melanin-bound antigen of the retinal pigment
      epithelium.
AB  - Retinal pigment epithelial cell fractions have been investigated for their
      capacity to induce experimental uveitis. Cells of the dark (melanotic) and light
      areas of the bovine RPE have subsequently been extracted by buffer, Triton X-100,
      sodium dodecyl sulfate (SDS), and treated with various reagents in order to study
      some characteristics of the antigen. The SDS-insoluble melanotic fraction,
      consisting of spindle-shaped, mature melanin granules, proved to be the most
      uveitogenic preparation. Using pertussis toxin as coadjuvant, 1 microgram of
      melanin-protein (3.4 x 10(6) granules) was able to induce experimental autoimmune
      anterior uveitis (EAAU) in Lewis rats. The pathogenic activity of the responsible
      pathogen (PEP-X) was not diminished by SDS, nor eliminated by mildly alkaline SDS
      or formic acid treatment. However, HCl-deproteinized granules were not
      uveitogenic. The results show that PEP-X is a highly stable melano-antigen that
      is probably covalently bound to the granule surface. This is the first time that
      a melanin-bound antigen has been demonstrated to evoke specific autoaggressive
      activity. EAAU could adoptively be transferred by sensitized and in vitro
      stimulated CD4 T-lymphocytes. The evoked inflammation started 3-4 days after
      injection, was similar to those induced by immunization, and consisted mainly of
      severe iridocyclitis accompanied by dense flare and cells in the anterior
      chamber. Choroiditis developed in severe cases of EAAU but no inflammation was
      detected in the retina, pineal gland or other organs of these rats. EAAU could
      not be transferred by serum. Immunized PVG rats and guinea-pigs did not develop
      ocular inflammation. In monkeys a high dose of antigen evoked a very mild EAAU
      accompanied by choroiditis. In view of its characteristics, EAAU may be a new
      model for human anterior uveitis.

PMID- 1358667
TI  - Proceedings of the 2nd International Conference on Longevity and Aging:
      Environmental and Nutritional Influences on Aging and Cancer.

PMID- 1358669
TI  - NMDA receptor-mediated long term modulation of electrically evoked field
      potentials in the rat medial vestibular nuclei.
AB  - The effect of high frequency stimulation (HFS) of the primary vestibular
      afferents on field potentials recorded in the ipsilateral Medial Vestibular
      Nuclei (MVN) was studied. Our results show that potentiation and depression can
      be induced in different portions of MVN, which are distinguishable by their
      anatomical organization. HFS induces potentiation of the monosynaptic component
      in the ventral portion of the MVN, whereas it provokes depression of the
      polysynaptic component in the dorsal portion of the same nucleus. The induction
      of both potentiation and depression was blocked under AP5 perfusion, thus
      demonstrating that NMDA receptor activation mediates both phenomena. Furthermore,
      the finding that the field potentials were not modified during perfusion with DL
      AP5, as previously reported, supports the hypothesis that NMDA receptors are not
      involved in the normal synaptic transmission from the primary vestibular afferent
      fibres, but are only activated following hyperstimulation of this afferent
      system. Our results suggest that the mechanisms of long term modification of
      synaptic efficacy observed in MVN may underlie the plasticity phenomena occurring
      in vestibular nuclei.

PMID- 1358668
TI  - Intracellular calcium and hormone release from nerve endings of the
      neurohypophysis in the presence of opioid agonists and antagonists.
AB  - Rat neural lobes and isolated nerve terminals from the neurohypophysis were
      stimulated in the presence of different opioid agonists and antagonists. The
      secretion of arginine vasopressin and oxytocin and rise in cytoplasmic calcium
      induced by depolarization were analyzed by radioimmunoassay and the fluorescent
      probe fura-2, respectively. The kappa-agonists dynorphin A(1-13) and dynorphin
      A(1-8) did not affect electrically evoked release of vasopressin, although
      oxytocin release was slightly reduced. U-50 488, a relatively specific kappa
      receptor agonist, had no effect on the amount of vasopressin or oxytocin
      secreted, although it significantly reduced K(+)-evoked changes in [Ca2+]i in
      isolated nerve endings. Two kappa-receptor antagonists, MR 2266 and diprenorphin,
      alone had no effect on vasopressin and oxytocin secretion from isolated nerve
      endings depolarized with potassium. Opioid agonists less selective for the kappa
      receptors, etorphin and ethylketocyclazocin, were found to inhibit the release of
      both vasopressin and oxytocin significantly. Naloxone, a nonselective opiate
      receptor antagonist, alone had no effect on vasopressin release but potentiated
      the electrically evoked release of oxytocin. Naloxone also could overcome the
      inhibitory effect of etorphin on oxytocin and vasopressin release observed after
      electrical stimulation of the neural lobe. A number of inconsistencies therefore
      exist between the effects of opioid agonists and antagonists on neuropeptide
      release and on the evoked changes in [Ca2+]i. In view of these inconsistencies
      and the high concentrations of opioid agonists and antagonists necessary to
      modify release, we conclude that it is doubtful that opioid molecules have a
      physiological role in controlling neurohypophysial secretion.

PMID- 1358671
TI  - Vermont physician assistants perform abortions, train residents.

PMID- 1358672
TI  - New drugs for asthma.
AB  - Several new drugs are now under development for the treatment of asthma, either
      as improvements to existing classes of therapy or as novel agents. Amongst
      bronchodilators, long-acting inhaled beta 2-agonists (salmeterol and formoterol)
      look very promising and there is also interest in selective phosphodiesterase
      inhibitors, K+ channel-openers and nitrodilators. There are several new inhaled
      corticosteroids under development and more selective agents include leukotriene
      antagonists, 5-lipoxygenase inhibitors, bradykinin and tachykinin antagonists and
      immunomodulators. In the future, adhesion molecule inhibitors and cytokine
      inhibitors may be developed.

PMID- 1358670
TI  - Brain cortical tissue levels of noradrenaline and its glycol metabolites: effects
      of ischemia and postischemic administration of idazoxan.
AB  - The brain noradrenaline (NA) system is known to modulate ischemic neuronal
      damage, and the turnover of NA has been suggested to increase in the early
      recovery period following cerebral ischemia. Using HPLC and gas chromatography
      mass spectrometry we analyzed the tissue levels of NA and its metabolites, 3,4
      dihydroxyphenylethyleneglycol (DHPG) and 3-methoxy-4-hydroxyphenylethyleneglycol
      (MHPG), in rat brain cortex after 10 min of forebrain ischemia followed by 1 h of
      recirculation. The effect of idazoxan, given in cerebro-protective doses, as a
      bolus of 0.1 mg.kg-1 immediately after ischemia followed by 10 micrograms.kg
      1.min-1 for 1 h, was also investigated. Ischemia decreased basal NA cortical
      levels from 384 ng/g tissue in control animals to 214 ng/g, while DHPG increased
      from 74 to 103 ng/g (+39%) and MHPG from 82 to 154 ng/g (+88%). Conjugated but
      not free DHPG increased, while both free and conjugated MHPG increased equally.
      The findings indicate an enhanced postischemic NA turnover with a major
      proportion of uptake and metabolism occurring extraneuronally, possibly secondary
      to a saturation of neuronal NA uptake in the postischemic phase. Idazoxan further
      increased NA turnover, as evidenced by higher postischemic levels of free MHPG
      and a higher MHPG/NA ratio. A correlation may exist between the protective action
      of idazoxan and its effect on NA turnover.

PMID- 1358673
TI  - Antihistamines in the treatment of asthma.
AB  - Histamine is an important mediator of asthma. The new anti-histamines which block
      histamine at the H1-receptor level also possess some anti-allergic properties. At
      current dosages they appear to be safe. These drugs are effective in the
      treatment of rhinitis and conjunctivitis but their role in asthma is still under
      investigation. At a dose higher than usually recommended, they were shown to
      block exercise-induced asthma and, inconstantly, the early phase reaction after
      allergen challenge. Their effect on the late phase allergic reaction as well as
      their clinical efficacy during trials is, however, less consistent. The
      indication of H1-blockers in the treatment of asthma is therefore limited,
      especially since doses higher than recommended may lead to adverse reactions.

PMID- 1358674
TI  - Breath-actuated inhalers in chronic asthma: comparison of Diskhaler and
      Turbohaler for delivery of beta-agonists.
AB  - An open, randomized, cross-over study was performed to compare the efficacy and
      acceptability of two breath-actuated inhalers, the Turbohaler (T) and Diskhaler
      (D), for delivery of beta-agonists. Thirty six adults with chronic asthma
      requiring beta-agonists four times daily were treated with terbutaline 500
      micrograms via T and salbutamol 400 micrograms via D four times daily, each
      period lasting four weeks. Additional bronchodilator via pressurized aerosol was
      permitted as required. Peak expiratory flow (PEF) was recorded in the morning
      (before and after beta-agonist) and in the evening. The mean morning PEF was
      higher during the first two weeks using T (295 l.min-1) than whilst using D (281
      l.min-1, p < 0.01), but this difference did not persist during the second two
      weeks and there were no differences in post-bronchodilator PEF or rescue beta
      agonist use. After four weeks, > 90% of patients used both inhaler devices
      efficiently and they were equally acceptable in terms of ease of use and
      convenience to carry. The Diskhaler and Turbohaler achieve similar clinical
      efficacy for delivery of beta-agonists.

PMID- 1358675
TI  - Dopaminergic stimulation up-regulates the in vivo expression of brain-derived
      neurotrophic factor (BDNF) in the striatum.
AB  - We investigated the effect of dopamine on the in vivo expression of brain-derived
      neurotrophic factor (BDNF) in the striatum of mouse. BDNF mRNA expression in the
      striatum, which was quantified with the reverse transcriptase polymerase chain
      reaction, was up-regulated from 2 h after oral administration of levodopa, a
      precursor of dopamine. The increase was sustained for 16 h. Co-administration of
      haloperidol partially inhibited dopamine-induced BDNF enhancement. These data
      suggest that dopaminergic stimulation directly promotes the expression of BDNF in
      the striatum in vivo.

PMID- 1358676
TI  - Structure of tubulin C-terminal domain obtained by subtilisin treatment. The
      major alpha and beta tubulin isotypes from pig brain are glutamylated.
AB  - Limited subtilisin digestion of the tubulin alpha, beta heterodimer has been used
      in this work to reduce the total number of tubulin isotypes from 20 for native to
      9 for subtilisin-cleaved tubulin. This indicates that the major part of tubulin
      heterogeneity is located at the C-terminus of the molecule. The C-terminal
      peptides of both alpha and beta subunits of tubulin were purified by anion
      exchange HPLC. Combined use of Edman degradation chemistry and mass spectrometry
      on the isolated peptides shows that subtilisin cleavage occurs at position Asp
      438 and His-406 of alpha and Gln-433 and His-396 of beta tubulin chains.
      Quantitative analysis of our data show that cleavage at positions His-406 (alpha)
      and His-396 (beta) occurs with a low efficiency and indicates that the major
      isotypes of pig brain tubulin are modified by sequential attachment of 1 to 5
      glutamic acid residues at positions Glu-445 or -435 of alpha and beta tubulin,
      respectively.

PMID- 1358677
TI  - An alternative mechanism for the nitrogen transfer reaction in asparagine
      synthetase.
AB  - In the absence of crystallographic data, the mechanism of nitrogen transfer from
      glutamine in asparagine synthetase (AS) remains under active investigation.
      Surprisingly, the glutamine-dependent AS from Escherichia coli (AsnB) appears to
      lack a conserved histidine residue, necessary for nitrogen transfer if the
      reaction proceeds by the accepted pathway in other glutamine amidotransferases,
      but retains the ability to synthesize asparagine. We propose an alternative
      mechanism for nitrogen transfer in AsnB which obviates the requirement for
      participation of histidine in this step. Our hypothesis may also be more
      generally applicable to other glutamine-dependent amidotransferases.

PMID- 1358678
TI  - Parathyroid carcinoma in a patient with non-secretory pituitary tumor: a variant
      of multiple endocrine neoplasia type-I?
AB  - We report a case of pituitary adenoma in association with parathyroid carcinoma
      as an unusual combination of multiple endocrine neoplasia (MEN). A 48-year-old
      man had a trans-sphenoidal hypophysectomy and transcranial partial removal of a
      recurrent pituitary chromophobe adenoma followed by a course of radiotherapy in
      1980. Four years later, he developed hypercalcemic crisis from a parathyroid
      carcinoma with invasion to the adjacent thyroid gland and skeletal muscle. A
      hemithyroidectomy and resection of the left lower parathyroid gland was
      performed. Three years later, he had local recurrence and anterior chest wall
      metastasis accompanied by hypercalcemia. After resection of the remnant and
      metastatic lesion, eucalcemia was achieved. There was no family history of
      endocrine tumors. This case illustrates the rare association of a malignant
      parathyroid tumor and a chromophobe adenoma of the pituitary as a variant of MEN
      syndrome.

PMID- 1358679
TI  - [The polyphosphoinisitide response evoked by different neuromediators after
      exposure to a helium-oxygen environment under increased pressure].
AB  - Male Wistar rats were subjected to normoxic helium-oxygen mixture under 40 kg/cm2
      pressure with subsequent decompression. Their brain's Ach, dopamine, glutamate,
      substance P were shown to change the turnover rate of the synaptosomal PPI. The
      findings suggest an unspecific mechanism of action of high tension helium on the
      neurons. The data obtained shows the high pressure neural syndrome not to be
      connected with metabolic change of a single neurotransmitter.

PMID- 1358680
TI  - Doyne Lecture. Rhodopsin and autosomal dominant retinitis pigmentosa.

PMID- 1358681
TI  - VIth Congress of Czechoslovak Immunologists. Banska Bystrica, September 16-20,
      1991.

PMID- 1358682
TI  - [Fundamentals of solders in dental technique].

PMID- 1358683
TI  - Purification of a mature form of 60 kDa heat-shock protein (chaperonin homolog)
      from porcine kidney and its partial amino acid sequence.
AB  - 1. We have purified a 58 kDa collagen-binding protein from a 4 M guanidine
      hydrochloride extract of porcine kidney. 2. This protein was identified as a
      mature form of 60 kDa heat-shock protein (HSP60, chaperonin homolog) based on its
      partial amino acid sequence. 3. Among 98 determined sequences of the porcine
      protein, 97 residues were identical with those deduced from nucleotide sequence
      of the cDNA encoding human HSP60.

PMID- 1358684
TI  - The de Watteville Memorial Lecture: reproductive technologies and genetic
      advances in obstetrics and gynecology.
AB  - Public fascination with genetics and the new reproductive technologies seem
      ubiquitious. Although interest in genetic causation for diseases is not new,
      attention is increasing. There are several predictable reasons for this. One is
      the overall decrease in deaths due to infection. As a result, genetic factors
      producing birth defects loom relatively larger. This is also coupled with the
      public's increased desire for the ideal pregnancy, especially given a decreased
      population rate. Finally, the public's appetite is whetted by the increasing
      number of heritable diseases whose molecular basis is being elucidated. We shall
      focus on three general areas in which genetic technology increasingly impacts
      upon the obstetrician/gynecologist: genetics of pregnancy losses, genetics of sex
      determination and the common gynecologic disorders, and finally prenatal genetic
      diagnosis, particularly in preimplantation genetics and recovering fetal cells
      from maternal blood. Most of these topics are discussed in a recent text, where
      extensive references are available.

PMID- 1358685
TI  - The impact of maternal age on pregnancy and its outcome.
AB  - There were 28,600 deliveries of 500 g or more to women at the Rotunda Hospital
      between January 1st 1985 and December 1st 1989. Of these, 595 were to women aged
      40 years and over. Thirty-five variables of clinical significance were analyzed,
      comparing those of 40 years of age and more with those under 40. The older group
      had significant increases in gestational diabetes, ante-partum hemorrhage, fetal
      distress, prematurity, low birth weight and perinatal mortality. Chromosome
      congenital abnormalities were significantly higher, particularly Down syndrome.
      There were significantly increased rates of induction and cesarean section in the
      older women. Some evidence of interaction of age with other factors was found,
      however these were difficult to separate out in the clinical setting. We
      therefore recommend it wiser to manage all elderly gravidas in a high risk manner
      dealing with cases individually within this framework. Intervention should,
      however, need to be justified in the older as in the younger woman.

PMID- 1358686
TI  - The preterm breech delivery in Zaria, northern Nigeria.
AB  - The preterm breech occurred in 31.21% of singleton breech presentations in a
      prospective study at Ahmadu Bello University Teaching Hospital (ABUTH), Zaria,
      Nigeria. The uncorrected perinatal mortality of 670.5 per 1000 deliveries was 1.7
      times that for term breech presentations. Failure to book for antenatal care
      (50.94%), admission of cases in the second stage of labor (21.84%) and
      intrauterine fetal death on admission (38.64%) were associated factors of the
      high perinatal mortality. The mortality was extremely high in the very low
      birthweight fetus (less than 1500 g) delivered vaginally. Moreover, the cesarean
      section rate was associated with a 2.4 times higher perinatal morbidity and
      mortality rates than vaginal delivery.

PMID- 1358687
TI  - Obstetric performance following conservative surgery for pelvic relaxation.
AB  - Over a period of three years (January 1987 to December 1990), 78 cases of
      conservative surgery for pelvic relaxation, either at our hospital or in some
      other hospitals, were studied. All of these patients were admitted in active
      labor or as cases of abortions. The complex nature of the problem of pelvic
      relaxation or genital prolapse is evident from the fact that we have encountered
      as many as six conservative operations in our series. The reproductive
      performance of a patient along with the time taken for the conception to occur
      after the surgery are emphasized in our study.

PMID- 1358688
TI  - Ectopic pregnancy among past IUD users.
AB  - The relationship between return to fertility and pregnancy outcome in women with
      IUD removal for planned pregnancy as well as the frequency of ectopic pregnancy
      among all former IUD users in comparison with the general population was studied.
      The cumulative conception rate in the group of women with IUD removal for planned
      pregnancy (n = 748) was 93.7% after 5 years, 93.4% being intrauterine and 0.3%
      ectopic. Rates of ectopic pregnancy in women with IUD removed for planned
      pregnancy were 2.7/1000 women, 3.6/1000 deliveries and 2.9/1000 pregnancies vs.
      3.9, 13.4 and 5.6 in the general population. Only when the number of deliveries
      is used as denominator, have these differences reached statistical significance
      (P less than 0.05). Except for bleeding/pain and PID removals (6.0 vs. 3.9), in
      all other groups of former IUD users the incidence of ectopic pregnancy was also
      lower than in the control group. From the results of this study it was concluded
      that former IUD users are not at an increased risk for ectopic pregnancy.

PMID- 1358689
TI  - Outcome of cryosurgery for cervical intraepithelial neoplasia in a developing
      country.
AB  - Over a 2-year period cryosurgery was used to treat 73 women who were diagnosed by
      colposcopy and histologic studies to have cervical intraepithelial neoplasia
      (CIN). Follow-up was achieved for 70% at 5 years, a significant attendance rate
      in a developing country. The primary cure rate was 88.5% at 1 year and 90% at 5
      years (excluding those lost to follow-up) in all patients with different grades
      of CIN. The therapy was free of major complications and we found no adverse
      effect of cryosurgery on subsequent reproductive function in those desiring
      pregnancy. We conclude that cryosurgery has gained wide acceptance in our
      geographic area particularly because of its low cost, efficacy and preservation
      of fertility. For these reasons we would strongly recommend its use provided
      adequate attention is paid to meticulous pretreatment evaluation and long-term
      follow-up after therapy.

PMID- 1358691
TI  - Choriocarcinoma presenting as pulmonary hydatid disease.

PMID- 1358692
TI  - Unusual fetal heart rate pattern with uniform rapid high frequency of change.

PMID- 1358690
TI  - Prospective analysis of short course chemotherapy in female genital tuberculosis.
AB  - Short course chemotherapy with 2SHRZ/7HR of 9 months duration was given in 41
      proven cases of female genital tuberculosis. Thirty-two (78%) patients completed
      9 months of therapy. Twenty-five (61%) were pronounced cured. Short course
      chemotherapy appears to be quite effective in patients of genital tract
      tuberculosis.

PMID- 1358693
TI  - Classification and staging of gynecologic malignancies. ACOG Technical Bulletin
      Number 155--May 1991 (replaces No. 47, June 1977).

PMID- 1358694
TI  - Voluntary testing for human immunodeficiency virus. ACOG Committee Opinion:
      Committee on Obstetrics: Maternal and Fetal Medicine. Number 97-September 1991.

PMID- 1358695
TI  - Fetal maturity assessment prior to elective repeat cesarean delivery. ACOG
      Committee Opinion: Committee on Obstetrics: Maternal and Fetal Medicine. Number
      98-September 1991 (replaces No. 77, January 1990).

PMID- 1358696
TI  - Report from the second ICM/WHO/UNICEF pre-congress workshop on midwifery
      education--action for safe motherhood.

PMID- 1358697
TI  - Ethical aspects of termination of pregnancy following prenatal diagnosis.

PMID- 1358698
TI  - Pregnancy-associated hypertension in Maputo. A study on maternal characteristics
      and perinatal outcome in 1275 consecutive cases.
AB  - A total of 1275 consecutive cases of pregnancy-associated hypertension were
      registered in the Maputo Central Hospital (corresponding to 2.9% of a total of
      43,794 city parturients). In the hypertensive and in the reference populations
      the following prevalence figures were registered, respectively: age below 25
      years, 52% and 23% (P < 0.0005); nulliparity, 33% and 19% (P < 0.0005); twin
      pregnancies, 3.9% and 1.7% (P < 0.0005); stillbirths, 5.7% and 2.3% (P < 0.0005);
      and low birthweight (LBW), 22.9% and 10.7% (P < 0.0005). In the hypertensive
      population the prevalence of LBW newborns was 20.1% in the liveborn group, while
      it was 68.4% in the stillborn group (P < 0.0005). In the ongoing perinatal audit
      it was found useful to review hypertensive women separately, in order to assess
      current routines in cases of pregnancy hypertension.

PMID- 1358699
TI  - Obstructed labor in Ibadan.
AB  - Over a period of 13 years, 380 cases of obstructed labor were managed amongst
      39,456 deliveries. Absent prenatal care and poor intrapartum care at peripheral
      hospitals were major contributing factors. The average duration of labor in those
      with obstruction was three times that in the normal obstetric population. About
      82% of patients with obstruction had an emergency cesarean section while 10% had
      destructive operations. The main etiological factor was unrecognised positional
      disproportion. Common associated complications were ruptured uterus, genital and
      wound sepsis. Maternal and perinatal morbidity and mortality were high. Adequate
      health education, incorporation of traditional birth attendants into health care
      programs and the provision of more health care centers will reduce the occurrence
      of this complication.

PMID- 1358700
TI  - Assessment of fetal well-being: fetal movement count versus non stress test.
AB  - In this prospective study, comparisons were made between the results of fetal
      movement count as performed by either the attending staff or by the patients
      using the non stress test (NST). A total of 283 NSTs were performed in 200
      patients who had singleton pregnancy of at least 32 weeks gestation with
      indications for assessment of fetal well-being. Fetal movement counts performed
      by the attending staff and by the patients were recorded on 241 and 170
      occasions, respectively. The results showed that the best correlation between
      fetal movement count by the attending staff with NST was when the criteria of
      three or more fetal movements within 10 min was used. Likewise, the best
      correlation between fetal movement count by patients with NST was found when ten
      fetal movements within 2 h was used as a cut off point. The result of this study
      suggests the usefulness of fetal movement count performed either by attending
      staff or patients as a cheap and effective method of screening for good fetal
      well-being in places where NST is not readily available and may also be used as a
      screening for patients prior to further evaluation.

PMID- 1358702
TI  - Ovarian masses in postmenopausal women.
AB  - In an attempt to evaluate the significance of malignant tumors in postmenopausal
      women, we reviewed the charts of 380 postmenopausal women over 50 years of age,
      operated on in our department for adnexal masses, from January 1st 1980 to
      December 31st, 1989. Two hundred and ninety-seven benign (78.2%) and 83 malignant
      (21.8%) tumors were found. In our group of patients the rate of malignancies
      increases significantly with the size of the lesion. Of the malignant tumors
      25.1% were in the age group 50-60 years, 16.3% in the age group 60-80 years and
      58.6%, a fourfold increase in the rate of malignancies, in the over 80 age group.
      Although surgery might pose problems in older patients, we conclude, on the basis
      of our experience, that surgical treatment should be considered for all adnexal
      masses in postmenopausal women.

PMID- 1358701
TI  - Haptoglobin as a sensitive marker of hemolysis in HELLP-syndrome.
AB  - In a prospective study we measured laboratory variables of hemolysis in 25
      patients with HELLP-syndrome. Reduced haptoglobin levels were observed in all 25
      patients at diagnosis. Elevated bilirubin and plasma hemoglobin levels were
      observed in 5/25 patients while an abnormal peripheral blood smear was found in
      11/25 patients. Our results suggest that haptoglobin is a sensitive parameter for
      early detection of moderate hemolysis in HELLP-syndrome and should be included in
      laboratory screening to aid diagnosis.

PMID- 1358703
TI  - Declining mortality in international sterilization services.
AB  - Between 1973 and 1988, AVSC supported 1,516,478 female sterilizations and 401,856
      vasectomies in 50 countries. Overall, 73 deaths were attributable to voluntary
      sterilization procedures (yielding mortality rates of 4.7 deaths per 100,000
      female sterilizations and 0.5 per 100,000 vasectomies). Causes of death, in order
      of frequency, were anesthesia (22), intestinal injury (20), infection (19), intra
      abdominal hemorrhage (6) and other (6). The female sterilization mortality rate
      declined from 7.1 per 100,000 procedures in 1973-1981 to 3.7 per 100,000 in 1982
      1988. Safer anesthesia practices and improved infection control contributed most
      to this decline. The mortality rate related to surgical errors declined
      proportionately less than the rates related to anesthesia and infection.
      Contraceptive sterilization has become a very safe procedure in these 50
      countries, where anesthesia (local and general), surgical technique
      (minilaparotomy and laparoscopy) and timing of the procedure (interval and
      postpartum) vary substantially. Future deaths will probably be rare. However,
      expert surgeons should review each case because identifying the most likely cause
      of death is always complex and these analyses help shape surgical contraception
      practices.

PMID- 1358705
TI  - Lyme disease during pregnancy. ACOG Committee Opinion: Committee on Obstetrics:
      Maternal and Fetal Medicine. Number 99--November 1991.

PMID- 1358704
TI  - Nonmalignant conditions of the breast. ACOG Technical Bulletin Number 156--June
      1991 (Replaces No. 71, September 1983).
AB  - The evaluation of benign conditions of the breast requires constant vigilance in
      relation to diagnosis, treatment, and, importantly, exclusion of carcinoma.
      Fortunately, the clinical presentation and epidemiologic considerations of the
      various benign lesions of the breast provide information permitting a fairly
      precise diagnosis. Fibrocystic changes, with its various subconditions, certainly
      is the most prominent benign condition, but other benign alterations occurring in
      the breast are also somewhat common. The management of fibroadenomas requires
      precise judgment and depends partly on the patient's age and the characteristics
      of the growth. Acute infections such as mastitis require prompt intervention and
      treatment. Recurring infections such as a subareolar abscess should be treated
      specifically in an aggressive and definitive manner. Infrequently occurring
      problems such as superficial thrombophlebitis, galactocele, and fat necrosis can
      be very uncomfortable, and occasionally, their diagnosis will be more difficult
      to establish. They, however, demand accurate diagnosis and definitive treatment.
      The axiom of excisional biopsy and histologic evaluation of any lesion that does
      not respond to treatment is the most important guideline in the treatment of
      benign breast disease.

PMID- 1358707
TI  - FIGO Committee for the Study of Ethical Aspects of Human Reproduction, Cairo
      Meeting, December 13th-14th, 1991.

PMID- 1358706
TI  - Second-look surgery for ovarian carcinoma. ACOG Committee Opinion: Committee on
      Gynecologic Practice. Number 100--November 1991.

PMID- 1358708
TI  - The effect of desogestrel for hormone replacement therapy on the blood lipid
      profiles of postmenopausal women.
AB  - OBJECTIVE: To determine the effect of a hormone replacement protocol containing
      conjugated equine estrogens and desogestrel (which has a highly selective
      progestogenic and low androgenic effect) as the progestogen, on the plasma lipid
      profile, as compared with two other hormone replacement treatments (HRT). METHOD:
      Eighty-nine healthy postmenopausal women were divided prospectively into four
      groups. A control group of 24 women did not receive HRT. Twenty-nine women
      received conjugated equine estrogen and medroxyprogesterone, and 13 women
      received a protocol containing estradiol, estriol and norethisterone acetate.
      Fasting blood lipid was taken at the end of each third cycle. The cumulative
      therapeutic response was calculated in each group as compared with initial values
      and between groups. Significance was analyzed by t-tests. RESULTS: A protocol
      containing desogestrel significantly decreased low-density lipoprotein
      cholesterol (27%; P < 0.05) and increased high-density lipoprotein cholesterol
      (HDL-C) by 30% (P < 0.05%) after 9 months. The ratio of total cholesterol to HDL
      C also decreased significantly (44%; P < 0.05). CONCLUSION: The most beneficial
      effect on plasma lipid profile was obtained with an HRT protocol containing
      desogestrel as the progesterone.

PMID- 1358709
TI  - Female voluntary surgical contraception via minilaparotomy under local
      anesthesia.
AB  - OBJECTIVE: To examine changes in prevalence and acceptance of sterilization
      methods in a developing country from 1986 to 1990. METHOD: Data from 5182
      voluntary female sterilizations performed at 52 service sites in Nigeria were
      retrospectively reviewed for sterilization method, anesthesia technique,
      demographic factors, and patient acceptance. RESULTS: The annual number of
      sterilization procedures increased dramatically over this period from 688 in 1986
      to 1911 in 1989. Overall, 74.3% of the procedures were performed by
      minilaparotomy under local anesthesia (ML/LA), 6% by laparoscopy/general
      anesthesia, and 19.7% by laparatomy/general anesthesia. ML/LA was found to be a
      very safe method, with a complication rate of 1.4%. 98.6% of ML/LA patients
      expressed complete satisfaction with the procedure. CONCLUSION: Female
      sterilization increased in acceptance in Nigeria over the period 1986-1990
      concomitant with the increased use of ML/LA. This approach is safe, cost
      effective, and appropriate for the developing world.

PMID- 1358710
TI  - The role of the village midwife in detection of high risk pregnancies and
      newborns.
AB  - The preliminary findings of a prospective study of perinatal, neonatal and
      maternal mortality carried out in a rural community of Sudan are reported. Out of
      6275 deliveries monitored over a period of 3 years, 150 stillbirths, 167 neonatal
      deaths and 27 maternal deaths were observed. An intervention program to upgrade
      the skills of the village midwives started in the middle of the second year.
      There was a 25% reduction in the risk of unfavorable outcome of pregnancy (i.e.
      stillbirth and neonatal death) in the third year relative to the first 2 years.
      Peer review of the 40 village midwives who took part in the study revealed their
      tremendous potentials in mobilization of mothers as well as participation in
      primary health care. Their role in detection of high risk pregnancies and
      newborns cannot be overemphasized.

PMID- 1358711
TI  - Maternal tetanus toxoid coverage during pregnancy in Ile-Ife, Nigeria.
AB  - A cluster survey on maternal tetanus toxoid (TT) coverage was carried out in the
      Ile-Ife Central Local Government Area. Out of the 896 mothers of babies 0-12
      months old who were interviewed, 668 (74.6%) claimed they received TT during
      pregnancy, this was confirmed in 37 (4.1%) and in only 25 (2.8%) of these cases
      could the babies be said to have been protected from neonatal tetanus (NNT) at
      birth. About 35% of the babies were delivered at home/churches where most babies
      with NNT are usually born.

PMID- 1358712
TI  - Histiocytosis X and vulvar ulceration.
AB  - Vulvar ulceration is a rare manifestation of histiocytosis X. A 13-year-old girl
      had a nonhealing vulvar ulcer for 1 year. She had been in remission from
      histiocytosis X and the ulcer was not recognised as a sign of disease recurrence
      until tissue biopsy was obtained for histopathological and immunohistochemical
      studies. This article stresses the importance of establishing an accurate
      diagnosis when chronic vulvar ulcers are encountered and reviews the literature
      on this uncommon presentation of histiocytosis X.

PMID- 1358713
TI  - The epidemiology of neural tube defects in Izmir, Turkey.

PMID- 1358714
TI  - Heparin-induced thrombocytopenia syndrome (HITS), complicated by bilateral
      femoral arterial thrombosis.

PMID- 1358716
TI  - Current status of cystic fibrosis carrier screening. ACOG committee opinion:
      committee on obstetrics: maternal and fetal medicine. Number 101--November 1991.

PMID- 1358715
TI  - Induction and augmentation of labor. ACOG Technical Bulletin Number 157--July
      1991.

PMID- 1358717
TI  - Placental pathology. ACOG committee opinion: committee on gynecologic practice.
      Number 102--December 1991.

PMID- 1358718
TI  - Anesthesia for emergency deliveries. ACOG committee opinion: committee on
      obstetrics: maternal and fetal medicine. Number 104--March 1992.

PMID- 1358719
TI  - Social issues in reproductive medicine.

PMID- 1358720
TI  - Risk factors for maternal mortality: results of a case-control study conducted in
      Conakry (Guinea).
AB  - OBJECTIVE: To assess the risk factors of maternal mortality in an urban area of
      West Africa (Conakry, capital of Guinea). METHOD: A case-control study where 102
      maternal deaths were compared with 338 control women who had given birth and
      survived, during 1 year (from July 1, 1989 to June 30, 1990). RESULT: Of all the
      socio-demographic variables studied, only a low family income (R = 2.6; 1.1-6.5)
      was found to be a risk factor for maternal death In the obstetrical part of the
      survey, neither parity nor the number or location of pre-natal consultations
      constituted risk factors. However, the presence during pregnancy or delivery of
      signs of infection (R = 3.7; 1.4-9.8), anemia (R = 2.1; 1.1-4.1), hypertension (R
      = 19.8; 5.8-67.8) and dystocia (R = 9.0; 3.7-21.5) were found to be the main
      predictive risk factors of maternal death. The maternal mortality risk was
      multiplied by 12 if the women had had a cesarean section, and by 4 in the case of
      complications in the post-partum period. CONCLUSION: To achieve substantial
      reductions in maternal mortality levels, work must be done on these specific risk
      factors, and future programs must urgently be concentrated on a higher standard
      of pre-natal monitoring, obstetrical emergency facilities and training of
      obstetrical staff.

PMID- 1358721
TI  - Management of patients with poor symphysis pubis-fundus growth by Doppler flow
      velocimetry of the umbilical artery--an effective method to detect the fetus at
      risk.
AB  - This study evaluated Doppler flow velocimetry of the umbilical artery in patients
      with suspected intrauterine growth retardation as detected by poor symphysis
      fundus growth (SFG). The sensitivity of Doppler in detecting light for
      gestational age babies and intrauterine growth retardation was poor. Antenatal
      complications, neonatal morbidity and perinatal mortality occurred significantly
      more frequently in patients with abnormal flow. Doppler flow velocimetry is an
      excellent test to identify babies at high risk for perinatal morbidity and
      mortality, when poor SFG is present.

PMID- 1358722
TI  - The use of intradepartmental audit to contain cesarean section rate.
AB  - In one department practicing critical review of indications for cesarean
      delivery, the overall LSCS rate was maintained at 12.3%, 11.1%, 11.2% and 11.4%
      for 1987, 1988, 1989 and 1990, respectively. A highly significant (P = 0.0013)
      reduction of 26.8% was observed in the LSCS rate for cephalo-pelvic disproportion
      between 1987 and 1990. Perinatal mortality rate per 1000 births remained low at
      8.25, 7.05, 9.39 and 5.83 for infants weighing 500 g or more.

PMID- 1358723
TI  - A role for lysosomes in scrapie pathogenesis.

PMID- 1358724
TI  - Amplification of members of the neurotransmitter transporter superfamily using
      PCR.

PMID- 1358725
TI  - The role of insulin in the regulation of AMP-activated protein kinase in
      lactating rat mammary gland.

PMID- 1358726
TI  - Localization of n-Chimaerin in rat brain, using antibodies raised against
      bacterially expressed trpE fusion proteins.

PMID- 1358727
TI  - Annulin, a protein expressed at limb segment boundaries in the grasshopper
      embryo, is homologous to protein cross-linking transglutaminases.
AB  - Annulin, a protein whose general stage- and position-specific expression pattern
      in the grasshopper embryo is described in the companion paper, is expressed in
      epithelial annuli in developing limbs. Here, we show that these annuli comprise
      narrow circumferential bands of epithelial cells at the boundaries of limb
      segments. At most boundaries, expression of annulin precedes the first
      morphological signs of segmentation. The most distal cells in a band underlie the
      boundary invagination. Bands arise in a stereotyped order and, within a band,
      expression occurs in an ordered circumferential progression. Annulin has a
      molecular weight of about 97 kDa and appears to be intracellular and peripherally
      associated with the inner leaflet of the cell membrane. Using the monoclonal
      antibody 7H7, two overlapping cDNA clones encoding this protein were isolated
      from an embryonic Schistocerca cDNA expression library. The nucleotide and
      deduced amino acid sequences indicate that the annulin protein does not contain
      either a signal sequence or a transmembrane domain. By sequence comparison,
      annulin appears to be a transglutaminase, one of a family of enzymes that have
      protein cross-linking activity. Its expression pattern within the limb and the
      embryo is associated with areas undergoing morphogenetic rearrangements,
      movements, or rapid cell division. It may stabilize cells under mechanical stress
      or participate in some other way in these morphogenetic activities.

PMID- 1358728
TI  - Two distal-less related homeobox-containing genes expressed in regeneration
      blastemas of the newt.
AB  - Urodeles, like the newt, are able to replace their limbs and tail following
      amputation by the formation of a blastema, a mass of proliferating mesenchymal
      cells originating from the tissue adjacent to the cut surface. As this capacity
      may involve genetic control, we investigated in adult tissues the expression of
      genes controlling embryonic development. We screened a newt cDNA library with a
      redundant oligonucleotide specific to the highly conserved third helix of the DNA
      binding domain of homeobox genes. Five classes of cDNA have been isolated. We
      report the nucleotide sequence and the tissue distribution of two of them, NvHBox
      4 and NvHBox-5. The amino acid sequences of both homeodomains are highly
      homologous (83 and 87% identity) to distal-less, a Drosophila homeobox gene
      expressed during the development of appendages. NvHBox-4 and NvHBox-5 express
      respectively 2.8 and 2 kb transcripts. The pattern of expression of both genes is
      identical in adult tissues of the newt. Polyadenylated transcripts are detectable
      in the forelimbs, hindlimbs, the tail, flank, and brain as well as in limb and
      tail blastemas. Analysis of dissected tissue from the hindlimbs indicated that
      the expression of both genes is restricted to the skin. This work is a first step
      toward understanding the possible relation between sustained expression of
      homeobox-containing genes in adult newt tissues and regeneration potential.

PMID- 1358729
TI  - Cloning and characterization of a novel Drosophila Wnt gene, Dwnt-5, a putative
      downstream target of the homeobox gene distal-less.
AB  - The Wnt gene family in vertebrates comprises at least 11 distinct genes but the
      only family member previously identified in Drosophila has been the segment
      polarity gene wingless (wg), the ortholog of vertebrate Wnt-1. In this report we
      describe the isolation of a novel Drosophila Wnt gene, Dwnt-5, which differs
      significantly from wg in both the pattern of its expression during embryogenesis
      and the predicted structure of its product. Dwnt-5 encodes a polypeptide of 112
      kDa, which is more than twice as large as the products of previously known Wnt
      genes. The protein shares homology with other Wnt sequences in its carboxy
      terminal half only and is most closely related to the products of vertebrate Wnt
      5a and Wnt-5b. Dwnt-5 is expressed in a complex pattern during Drosophila
      embryogenesis. At the extended germ band stage, however, transcripts accumulate
      specifically in the nascent limb primordia of the head and thoracic segments. We
      show that this elevated expression depends on the activity of the homeobox gene
      Distal-less (Dll) and suggest that the Dwnt-5 gene may constitute a downstream
      target of Dll that acts in the specification of these primordia.

PMID- 1358730
TI  - Contractile protein isoforms in muscle development.
AB  - The contractile proteins of skeletal muscle are often represented by families of
      very similar isoforms. Protein isoforms can result from the differential
      expression of multigene families or from multiple transcripts from a single gene
      via alternative splicing. In many cases the regulatory mechanisms that determine
      the accumulation of specific isoforms via alternative splicing or differential
      gene expression are being unraveled. However, the functional significance of
      expressing different proteins during muscle development remains a key issue that
      has not been resolved. It is widely believed that distinct isoforms within a
      family are uniquely adapted to muscles with different physiological properties,
      since separate isoform families are often coordinately regulated within
      functionally distinct muscle fiber types. It is also possible that different
      isoforms are functionally indistinguishable and represent an inherent genetic
      redundancy among critically important muscle proteins. The goal of this review is
      to assess the evidence that muscle proteins which exist as different isoforms in
      developing and mature skeletal and cardiac muscles are functionally unique. Since
      regulation of both transcription and alternative splicing within multigene
      families may also be an important factor determining the accumulation of specific
      protein isoforms, evidence that genetic regulation rather than protein coding
      information provides the functional basis of isoform diversity is also examined.

PMID- 1358731
TI  - Cholinergic differentiation of rat sympathetic neurons in culture: effects of
      factors applied to distal neurites.
AB  - Cholinergic properties are induced in sympathetic neurons by several factors
      applied to entire neurons in culture. Evidence from work with the rat sweat gland
      model indicates that factors located in target tissues can induce cholinergic
      differentiation in vivo. We now report that when leukemia inhibitory factor
      (LIF), heart cell-conditioned medium (HCCM), or dermal fibroblast-conditioned
      medium (DFCM) is applied to only distal neurites in compartmented cultures of rat
      sympathetic neurons, the neurons exhibit an increase in specific choline
      acetyltransferase activity and a concomitant decrease in levels of tyrosine
      hydroxylase. LIF, HCCM, and DFCM also induce neurite fasciculation, thus
      suggesting an additional role of cholinergic switching factors in regulating axon
      axon and/or axon-substrate adhesion. These results demonstrate that rat
      sympathetic neurons have the cellular machinery to respond to cholinergic
      differentiation cues located in peripheral targets, analogous to the response to
      nerve growth factor.

PMID- 1358732
TI  - Standardization of the immunopharmacology of natural and synthetic
      immunomodulators. Proceedings of a symposium. Annecy, France, 15-17 May 1991.

PMID- 1358734
TI  - When and why do brain cells die?

PMID- 1358735
TI  - [Reactions of various neuroregulatory systems in astronauts after a 366-day space
      flight].

PMID- 1358733
TI  - Second signal for T lymphocyte activation: multiple targets for pharmacological
      modulation.
AB  - Complete T cell activation requires at least two signals. The first is delivered
      through the antigen-specific T cell receptor, whereas the second is generated by
      cognate interactions through adhesion molecules of T cells and antigen-presenting
      cells and/or by cytokines produced by antigen-presenting cells. The delivery of
      the two signals results in gene transcription, cytokine secretion, expression of
      new cell surface molecules including cytokine receptors, and cellular
      proliferation. Reference immunosuppressive agents were shown to act at different
      subsequent stages of T cell activation and proliferation. Among immunostimulating
      compounds, those which can enhance T cell responses are likely to modulate or
      replace the second signal in T cell activation, or alternatively, to act at later
      stages such as cytokine secretion, cytokine receptor expression or response to
      cytokine signals. For the purpose of in vitro evaluation of the activity of
      immunomodulators on the second signal of T cell activation, we devised a model of
      accessory cell depletion and reconstitution. This model allows the capacity of a
      given compound to enhance surface adhesion molecule expression or to trigger
      monocyte cytokine synthesis to be tested, and these effects to be assessed on T
      cell proliferation.

PMID- 1358736
TI  - [Severe psychiatric disorders associated with severe acute colitis].
AB  - Acute colitis occurring in patients suffering from psychiatric illnesses is
      believed to be linked to the intake of psychotropes. From 1983 to 1989, the
      authors observed, in three Hepato-gastroenterology units, 10 cases of acute
      colitis in patients suffering from serious psychiatric disorders, most of them
      inpatients of mental hospitals. The detailed study of 7 of these cases emphasized
      a certain number of common features: there was no previous history of digestive
      disease, the psychiatric illness was serious and longstanding, acute colitis was
      severe, and there was no recurrence during clinical and endoscopic follow-up
      averaging 4.3 years. Of these 7 patients, 2 were not taking psychotropes at the
      time of colitis or after, 2 had discontinued their treatment for a few days, and
      2 had not stopped taking psychotropes. One patient died. The short-term and long
      term evolution in these cases was not influenced by the intake or not of
      psychotropes. The pathogeny of this colitis is yet to be determined: infection is
      the most likely origin.

PMID- 1358737
TI  - [Benign papillomatosis of Wirsung's duct associated with adenomyoma of the distal
      common bile duct].
AB  - We report the case of a 42 year-old man, with a history of alcohol and tobacco
      abuse, who was referred for suspicion of carcinoma of the head of pancreas.
      Pancreatoduodenectomy was performed. Histological study demonstrated obstructive
      benign adenomyoma of the distal common bile duct associated with villous
      papillomatosis of the pancreatic ducts and patchy lesions of chronic
      pancreatitis. Two years later, the patient was completely asymptomatic, but the
      risk of malignant transformation of villous papillomatosis requires periodic
      examination of the remaining pancreas and biliary tract.

PMID- 1358739
TI  - PCNA-positive cell distribution in depressed types of early carcinoma and adenoma
      of the large intestine.

PMID- 1358738
TI  - Influence of plasma proteinase inhibitors and the secretory leucocyte proteinase
      inhibitor on pancreatic elastase-induced degradation of some plasma proteins.
AB  - Pancreatic elastase-induced degradation of some plasma proteins was studied in an
      in vitro model. The digestion was correlated with the degree of saturation of the
      alpha 1-proteinase inhibitor (alpha 1PI) and also with varying amounts of
      secretory leucocyte proteinase inhibitor (SLPI). SLPI was found to inhibit
      pancreatic elastase showing a Ki of about 10(-7) M for the complex. On the
      addition of human pancreatic elastase to plasma cleavage of C3, kininogen,
      fibrinogen and fibronectin was observed when the alpha 1PI approached saturation.
      In the present in vitro model it was possible to block the cleavage of the four
      plasma proteins, mentioned above completely with SLPI. Addition of the inhibitor
      also decreased the consumption of alpha 1PI.

PMID- 1358740
TI  - Endotoxin-induced alterations in rat colonic water and electrolyte transport.
AB  - This study examines the effects of endotoxin on intestinal water and electrolyte
      transport in adult male rats. Endotoxin (1.55 mg/kg, intravenously) reduced in
      vivo colonic saline absorption 61% in 1 hour. In vitro unidirectional and net
      22Na and 36Cl fluxes showed that endotoxin significantly decreased net colonic
      22Na absorption compared with control colons (0.3 +/- 1.7 vs. 4.8 +/- 1.1
      microEq/h x cm2). Although endotoxin had no significant effect on basal short
      circuit current (Isc) and conductance, 3H-inulin flux studies suggested an
      increase in colonic permeability. Isc responses to the 5'-cyclic adenosine
      monophosphate (cAMP)-dependent secretagogues prostaglandin E2 (1 mumol/L) and
      vasoactive intestinal peptide (0.1 mumol/L) were diminished by 80% and 50%,
      respectively. However, cytosolic cAMP-dependent protein kinase activity under
      basal and stimulated (6 mumol/L 8-bromo-cAMP) conditions was not altered by
      endotoxin treatment. The Isc responses to 10 mumol/L bethanechol, a Ca(2+)
      dependent agonist, were not effected by endotoxin treatment. It was concluded
      that endotoxin significantly affects colonic transport function and may
      contribute to the development of diarrhea in inflammatory bowel diseases.

PMID- 1358741
TI  - Colorectal cancer risk and mortality in patients with ulcerative colitis.
AB  - A regional inception cohort of 1161 ulcerative colitis (UC) patients was followed
      up from diagnosis to the end of 1987. The follow-up rate for death and occurrence
      of cancer was 99.9% (median observation time, 11.7 years; range, 0-26 years). One
      hundred forty-one deaths were observed, 26 caused by UC or complications thereof.
      No significant excess mortality was found after the first year, but in the year
      of diagnosis the relative risk of death was 2.4 (P < 0.001). The cumulative
      colectomy rate 25 years after diagnosis was 32.4%. The initial extent of disease
      significantly influenced the colectomy probability, being 35% in total colitis,
      19% in substantial colitis, and 9% in distal colitis within the first 5 years
      after diagnosis. Six patients developed colorectal cancer within the observation
      period. Compared with the expected number of 6.6, the relative risk for patients
      with UC was 0.9. The calculated cumulative cancer incidence was 3.1% after 25
      years (95% confidence limits, 0.0-6.8). The calculated lifetime risk (0-74 years)
      for development of colorectal cancer was 3.5% for UC patients compared with 3.7%
      for the Danish population. It is concluded that with an active approach to
      medical and surgical treatment, as practiced here, patients whose colons are left
      intact bear no significantly increased risk of colorectal malignancy.

PMID- 1358742
TI  - Neoplasia and hyperplasia of large bowel: focal lesions in an abnormal
      epithelium.
AB  - Expression of brush border hydrolases can reflect the state of differentiation of
      an epithelium. To determine if expression of these enzymes is disordered in
      patients with neoplastic or hyperplastic lesions, the activities of alkaline
      phosphatase, maltase, and dipeptidyl peptidase IV were measured
      spectrophotometrically in colonoscopic biopsies from the proximal and distal
      colon and rectum in 50 controls, 17 patients with large bowel adenomas, 29 with
      carcinoma, and 9 with hyperplastic polyps. In normal controls, a descending
      cecorectal gradient of alkaline phosphatase activities and an ascending gradient
      of maltase activities were seen (P < 0.001). Though regional patterns of
      expression were generally preserved in disease groups, there were significant
      differences of activities across patient groups for alkaline phosphatase (greater
      in cancer, adenoma, and hyperplastic groups than in normals; P < 0.05) and for
      dipeptidyl peptidase IV (greater in hyperplastic polyp group than normals,
      greater in adenoma than cancer group; P < 0.05). Compared with normal controls,
      abnormalities of site-specific activities were confined to the rectum in patients
      with adenoma (maltase decreased, P = 0.02; dipeptidyl peptidase IV increased, P <
      0.01) or with carcinoma (alkaline phosphatase increased, P = 0.03) but dipeptidyl
      peptidase IV activities were increased in all regions in bowels bearing
      hyperplastic polyps (P < 0.01). These data suggest that neoplastic and
      hyperplastic lesions, while focal in nature, occur in large bowel epithelium,
      which is diffusely abnormal in terms of its expression of these enzymes.

PMID- 1358743
TI  - Neoplastic progression in ulcerative colitis: histology, DNA content, and loss of
      a p53 allele.
AB  - Neoplastic progression in patients with chronic ulcerative colitis (UC) is
      characterized by the development of epithelial dysplasia, which is accompanied by
      genetic abnormalities that can be detected by flow cytometric and molecular
      biologic methods. Distribution of and correlation between histologic
      abnormalities, DNA content, and loss of heterozygosity for a p53 allele (p53 LOH)
      in the colons of nine UC patients were analyzed. Loss of a p53 allele was found
      in 85% (22/26) of biopsy specimens classified histologically as carcinoma, 63%
      (25/40) of biopsy specimens with high grade dysplasia, and 33% (7/21) of biopsy
      specimens with low grade dysplasia. Loss of heterozygosity for p53 was also found
      in 9% (5/57) of biopsy specimens indefinite for dysplasia and in 1/18 biopsy
      specimens negative for dysplasia, showing that this genetic change may occur
      early in the histological progression towards carcinoma. Aneuploid DNA contents
      were more common than p53 LOH in regions with negative, indefinite or low grade
      dysplastic histology; moreover, p53 LOH was detected only in aneuploid cells and
      not in diploid epithelium. Aneuploidy alone was not as specific a marker for the
      concomitant presence of dysplasia or carcinoma in a biopsy sample as aneuploidy
      combined with p53 LOH. These findings show that aneuploidy may precede both p53
      LOH and epithelial dysplasia. Two UC patients' colons contained geographically
      separated clones of cells with different aneuploidies that also showed loss of
      different p53 alleles, suggesting that neoplasia may arise within different
      populations of cells in separate areas of the same colon.

PMID- 1358744
TI  - In vivo effects of indomethacin on the activity of metal-containing enzymes.
AB  - 1. Indomethacin injected subcutaneously at a single "ulcerogenic" dose decreased
      aminooxidase and leucine aminopeptidase activity and did not change alcohol
      dehydrogenase and ceruloplasmin activity. 2. Indomethacin administered at an oral
      "therapeutic" dose inhibited aminooxidase activity in small intestinal mucosa but
      not in liver and did not change leucine aminopeptidase activity in blood, liver
      and intestinal mucosa; it, however, increased alcohol dehydrogenase and
      ceruloplasmin activity. 3. The decreased activity of ceruloplasmin and alcohol
      dehydrogenase by metal deficiency increased after oral indomethacin treatment,
      reaching the control values when indomethacin was chelated with copper. 4. The
      results suggest the participation of endogenous metals in the indomethacin
      effect.

PMID- 1358745
TI  - Absence of mitochondrial beta-adrenoceptors in guinea pig myocardium: evidence
      for tissue disparity.
AB  - 1. Binding sites in guinea pig myocardial tissue labelled by (-)-[125I]
      cyanopindolol (CYP) were investigated using differential centrifugation and
      autoradiographic techniques. Autoradiographs of myocardial sections (0.1 microns)
      indicated (-)-[125I]CYP binding to sarcolemmal membrane. A low density of binding
      sites was observed to mitochondria. 2. Binding studies were performed in
      subcellular fractions. The density of binding sites in the mitochondrial fraction
      (36.1 +/- 9.4 fmol/mg protein) was less than 10% that in the sarcolemmal membrane
      (371.7 +/- 38.2 fmol/mg protein). The beta 1/beta 2-adrenoceptor subtype ratio in
      the mitochondrial fraction (83.3/16.7) was similar to that in the sarcolemmal
      fraction (87.1/12.9). 3. Ouabain (100 microM), in the presence of sodium azide
      (0.4 mM), inhibited a Na+K+ stimulated ATPase activity (1.0 +/- 0.2 mumol Pi/mg
      protein/hr reduction), indicating a low but significant level of sarcolemmal
      contamination of the mitochondrial fraction. 4. The study showed beta
      adrenoceptors in guinea pig heart are located primarily on the sarcolemmal
      membrane of myocardium. No evidence was obtained for beta-adrenoceptors over
      mitochondria, as has been suggested in other tissues and species, but that this
      binding was to sarcolemmal inclusions in the mitochondrial fraction.

PMID- 1358746
TI  - Alpha 1-adrenoceptor blocking activities of bevantolol hydrochloride(NC-1400) and
      labetalol in rat isolated thoracic aorta--do they distinguish between subtypes?
AB  - 1. alpha 1-adrenoceptor blocking activity of bevantolol(NC-1400) was tested in
      the rat thoracic aorta, comparing with that of labetalol. 2. In alpha 1
      adrenoceptor blocking activity, bevantolol(NC-1400) was 1/20th as potent as
      labetalol. 3. The pA2 values of bevantolol(NC-1400) and labetalol estimated in
      the rat thoracic aorta were compared with those in the rabbit thoracic aorta,
      which were reported by Takayanagi et al. [Takayanagi I., Kizawa Y., Iwasaki S.
      and Nakagoshi A. (1987) Gen. Pharmac. 18, 87-89]. 4. The pA2 values of
      bevantolol(NC-1400) and labetalol were approximately 1 order of magnitude higher
      in rat aorta than in rabbit aorta, suggesting that both the drugs distinguish
      between subtypes of alpha 1-adrenoceptors.

PMID- 1358748
TI  - CFU-S and haematopoietic microenvironment in mice after fractionated irradiation.
      A study on spleen colonies.
AB  - The paper is aimed at evaluating the quantity and quality of the haematopoietic
      stem cells, CFU-S, in the bone marrow and the functional effectiveness of the
      haematopoietic microenvironment of the spleen in two time intervals after
      repeated exposure of mice to doses of 0.5 Gy gamma-rays once a week (total doses
      of 12 and 24 Gy). After irradiation, bone marrow was cross-transplanted between
      fractionatedly irradiated and control mice. The parameter evaluated were numbers
      of spleen colonies classified into size categories. The data obtained provide
      evidence for a significant damage to the CFU-S, concerning both their number and
      proliferation ability, after both total doses used. The functional effectiveness
      of the haematopoietic microenvironment of the spleen was impaired only in bone
      marrow recipients receiving a transplant after having been exposed to a total
      dose of 24 Gy; this dose combined with subsequent pre-transplantation irradiation
      resulted in a marked suppression of cell production within the spleen colonies
      formed from a normal bone marrow on the spleens of fractionatedly irradiated
      mice.

PMID- 1358747
TI  - Influences of dopamine receptors on chewing behaviour in rats.
AB  - 1. Intraperitoneal (i.p.) injection of different doses of pilocarpine induced
      purposeless chewing in rats. Physostigmine (i.p.), but not neostigmine (i.p.)
      also induced chewing behaviour. 2. Subcutaneous (s.c.) pretreatment of animals
      with the D-1 receptor blocker SCH 23390 decreased the number of chews induced by
      pilocarpine. 3. The D-2 dopamine antagonist sulpiride (i.p.) and anticholinergic
      atropine (i.p.) pretreatment also decreased the frequency of chews induced by the
      drug. 4. The response induced by pilocarpine (1 mg/kg i.p.) also was dose
      dependently decreased in animals pretreated with apomorphine (0.25-1 mg/kg s.c.).
      5. Administration of low doses of apomorphine (s.c.) also induced chewing, which
      was decreased with increasing the doses of the drug. 6. Chewing-induced by
      apomorphine was decreased by sulpiride or atropine and increased by SCH 23390
      pretreatment. 7. Single administration of D-2 dopamine agonist bromocriptine also
      showed a slight but significant purposeless chewing, which was decreased by
      sulpiride pretreatment. 8. Single administration of D-2 agonist quinpirole, D-1
      agonist SKF 38393 or D-1 antagonist SCH 23390, but not sulpiride caused a slight
      chewing. 9. It may be concluded that D-1 or D-2 activation exert opposite
      influences on chewing behaviour in rats, although to prove this effect more
      elucidation is needed.

PMID- 1358749
TI  - TCP pilus biosynthesis in Vibrio cholerae O1: gene sequence of tcpC encoding an
      outer membrane lipoprotein.
AB  - The nucleotide sequence of the tcpC gene has been determined. It encodes a 53995
      Da protein precursor with a signal sequence and cleavage site typical of a number
      of outer membrane lipoproteins, which are cleaved by the equivalent of signal
      peptidase II (Lsp) of Escherichia coli. The location of the tcpC gene is such
      that it is predicted to be translationally coupled to the 5' and 3' flanking
      genes, tcpY and tcpD, respectively, indicating that it forms part of an operon.
      Together with the lipoprotein signal sequence and the several hydrophobic domains
      it seems likely that TcpC is a surface-anchored trans-outer membrane lipoprotein.

PMID- 1358750
TI  - Bacterial gamma-glutamyltranspeptidases: comparison of Escherichia coli and
      Pseudomonas gamma-glutamyltranspeptidase.
AB  - A high-level expression system for the Escherichia coli HB101 gamma
      glutamyltranspeptidase (GGT) gene was constructed to obtain a sufficient amount
      of the enzyme for structural studies. About 300 mg of the enzyme was purified
      from 2 1 of culture broth. Both subunits were needed to reconstitute GGT
      activity. The E. coli GGT and the Pseudomonas GGT were compared with respect to
      catalytic properties and immunological relationships. Both enzymes showed
      different acceptor specificities. Relatively high immunocross-reactivity was
      observed between the small subunits of both enzymes by Western blot analysis
      using antibodies prepared against either enzyme.

PMID- 1358751
TI  - Nonrandom distribution of chloroplast recombination events in Chlamydomonas
      reinhardtii: evidence for a hotspot and an adjacent cold region.
AB  - Intermolecular recombination of Chlamydomonas chloroplast genes has been analyzed
      in sexual crosses and following biolistic transformation. The pattern and
      position of specific exchange events within 15 kb of the 22-kb inverted repeat
      have been mapped with respect to known restriction fragment length polymorphism
      markers that distinguish the chloroplast genomes of the interfertile species
      Chlamydomonas reinhardtii and Chlamydomonas smithii. Recombinant progeny were
      selected from two- and three-factor crosses involving point mutations conferring
      herbicide (dr) and antibiotic resistance (er and spr) in the psbA, 23S and 16S
      ribosomal RNA genes, respectively. Exchange events were not randomly distributed
      over the 15-kb region, but were found to occur preferentially in a 0.7-kb
      sequence spanning the 3' end of the psbA gene and were much less common in an
      adjacent region of ca. 2.0 kb. These findings are corroborated by data showing
      that the dr mutation is unlinked genetically (3% recombination/kb) to the er and
      spr rRNA mutations, which are themselves linked and show ca. 1% recombination/kb.
      This discrepancy is significant since the dr-er and er-spr intervals are about
      the same length (ca. 7 kb). During chloroplast transformation, the 0.7-kb
      recombination hotspot also functions as a preferential site for exchange events
      leading to the integration of donor psbA gene sequences. The 0.7-kb hotspot
      region contains four classes of 18-37-bp direct repeats also found in other
      intergenic regions, but no open reading frame. Using deletion constructs in a
      chloroplast transformation assay, the hotspot was localized to a 500-bp region
      that lacks most of these repeats, which suggests that the repeats themselves are
      not responsible for the increased recombination frequency. Within this region, a
      400-bp sequence is highly conserved between the chloroplast genomes of C.
      reinhardtii and C. smithii and includes several structural motifs characteristic
      of recombination hotspots in other systems.

PMID- 1358752
TI  - Patterns of naturally occurring restriction map variation, dopa decarboxylase
      activity variation and linkage disequilibrium in the Ddc gene region of
      Drosophila melanogaster.
AB  - Forty-six second-chromosome lines of Drosophila melanogaster isolated from five
      natural populations were surveyed for restriction map variation in a 65-kb region
      surrounding the gene (Ddc) encoding dopa decarboxylase (DDC). Sixty-nine
      restriction sites were scored, 13 of which were polymorphic. Average
      heterozygosity per nucleotide was estimated to be 0.005. Eight large (0.7-5.0 kb)
      inserts, two small inserts (100 and 200 bp) and three small deletions (100-300
      bp) were also observed across the 65-kb region. We see no evidence for a
      reduction in either nucleotide heterozygosity or insertion/deletion variation in
      the central 26-kb segment containing Ddc and a dense cluster of lethal
      complementation groups and transcripts (greater than or equal to 9 genes)
      compared to that seen in the adjacent regions (totaling 39 kb) in which only a
      single gene and transcript has been detected, or to that observed for other gene
      regions in D. melanogaster. The distribution of restriction site variation shows
      no significant departure from that expected under an equilibrium neutral model.
      However insertions and deletions show a significant departure from neutrality in
      that they are too rare in frequency, consistent with them being deleterious on
      average. Significant linkage disequilibrium among variants exists across much of
      the 65-kb region. Lower regional rates of recombination combined with the
      influence of polymorphic chromosomal inversions, rather than epistatic selection
      among genes in the dense cluster, probably are sufficient explanations for the
      creation and/or maintenance of the linkage disequilibrium observed in the Ddc
      region. We have also assayed adult DDC enzyme activity in these same lines.
      Twofold variation in activity among lines is observed within our sample.
      Significant associations are observed between level of DDC enzyme activity and
      restriction map variants. Surprisingly, one line with a 5.0-kb insert within an
      intron and one line with a 1.5-kb insert near the 5' end of Ddc each show normal
      adult DDC activities.

PMID- 1358754
TI  - Genetic variability in a family of satellite DNAs from tilapia (Pisces:
      Cichlidae).
AB  - We have cloned and sequenced members of a family of satellite DNAs from three
      genera of the tilapiine tribe of fishes: Oreochromis, Sarotherodon, and Tilapia.
      The satellite DNAs, visualized as intensely staining bands following
      electrophoretic separation of EcoRI-digested genomic DNA, consist of three size
      variants differentially distributed in the various tilapiine species. The sizes
      of the monomers are approximately 237 bp (type I), 230 bp (type II), and 209 bp
      (type III). Several cloned monomers were sequenced from Oreochromis niloticus
      (type III), Oreochromis placidus (types I and II), Sarotherodon galilaeus (type
      I), Tilapia zillii (type I), and Tilapia rendalli (type I). Comparison of derived
      consensus sequences for the monomer units of the satellite DNAs revealed sequence
      identities within and between species that ranged from 89 to 96%. The type II and
      type III size variants appear to have arisen by deletions of 9 and 29 bp,
      respectively, within different regions of the type I satellite. Hybridization of
      a cloned monomer satellite from O. niloticus (type III) to PalI digests of
      genomic DNA from all three genera detected polymorphic, high molecular weight
      restriction fragments that produced fingerprint-like patterns. The complexity of
      these DNA fingerprints varied from one species to another, suggesting a markedly
      different genomic organization for these polymorphic satellite DNAs.

PMID- 1358753
TI  - Comparative studies of Drosophila Antennapedia genes.
AB  - The Antennapedia (Antp) homeotic gene of Drosophila melanogaster controls cell
      fates and pattern formation in the epidermis, nervous system and mesoderm of
      thoracic segments. Its expression is controlled at the levels of transcription,
      alternative RNA splicing, polyadenylation and translation. Two nested Antp
      transcription units extend over 103 kb and produce sixteen different transcripts.
      We have compared the Antp genes of Drosophila virilis, Drosophila subobscura and
      D. melanogaster to determine which structural features are conserved and
      therefore may be important to the gene's function. The overall gene structures
      are similar. There are many conserved sequence blocks throughout the large
      introns, at least 15 kb upstream of the first promoter, and at least 3 kb
      downstream of the last polyadenylation site. Intron and exon sequence
      conservation around alternative splice sites indicates that alternative protein
      coding forms may also be conserved. Protein coding potential is perfectly
      conserved around the C-terminal homeodomain, well conserved in the N-terminal
      region, and more variable in the middle. The large size of the Antp gene may
      reflect a large number of control elements necessary for appropriate Antp protein
      expression. The conservation of transcript complexity suggests functional
      requirements for the different protein forms.

PMID- 1358755
TI  - Recognition of the surface of a homeo domain protein.
AB  - Homeo domain proteins exhibit distinct biological functions with specificities
      that cannot be predicted by their sequence specificities for binding DNA.
      Recognition of the surface of the Oct-1 POU homeo domain provides a general model
      for the contribution of selective protein-protein interactions to the functional
      specificity of the homeo domain family of factors. The assembly of Oct-1 into a
      multiprotein complex on the herpes simplex virus alpha/IE enhancer is specified
      by the interactions of its homeo domain with ancillary factors. This complex (C1
      complex) is composed of the viral alpha TIF protein (VP16), Oct-1, and one
      additional cellular component, the C1 factor. Variants of the Oct-1 POU homeo
      domain were generated by site-directed mutagenesis, which altered the residues
      predicted to form the exposed surface of the domain-DNA complex. Proteins with
      single amino acid substitutions on the surface of either helix 1 or 2 of the Oct
      1 POU homeo domain had decreased abilities to form the C1 complex. The behavior
      of these mutants in a cooperative DNA-binding assay with alpha TIF suggested that
      the Oct-1 POU homeo domain is principally recognized by alpha TIF in the C1
      complex. The preferential recognition of Oct-1 over the closely related Oct-2
      protein is critically influenced by a single residue on the surface of helix 1
      because the introduction of this residue into the Oct-2 POU homeo domain
      significantly enhanced its ability to form a C1 complex.

PMID- 1358756
TI  - A single amino acid exchange transfers VP16-induced positive control from the Oct
      1 to the Oct-2 homeo domain.
AB  - The selective association of the herpesvirus trans-activator VP16 with the human
      Oct-1 homeo domain is a model for differential positive transcriptional control
      by homeo domains. VP16 discriminates between the closely related homeo domains of
      Oct-1 and Oct-2 by distinguishing among their seven amino-acid differences; these
      differences lie on the surface that is thought to be accessible when the homeo
      domain is bound to DNA. Only two of these seven differences are recognized by
      VP16, one in each of the first two alpha-helices of the tri-alpha-helical homeo
      domain. The major determinant for selective association with VP16 in vitro and
      VP16-induced positive control in vivo is a single glutamic acid residue at
      position 22 in the first alpha-helix of the Oct-1 homeo domain, but the acidic
      properties of this residue are not critical for association with VP16 in vitro or
      in vivo, because it can be replaced by glutamine with little or no deleterious
      effect. Mere replacement of the single corresponding alanine residue in the Oct-2
      homeo domain with the key glutamic acid residue is sufficient to confer on the
      Oct-2 homeo domain the ability to associate with VP16 in vitro and respond to
      VP16-induced positive control in vivo. Thus, the specificity of homeo domain
      positive control can be conferred by a single amino acid difference.

PMID- 1358758
TI  - Synergistic activation of the insulin gene by a LIM-homeo domain protein and a
      basic helix-loop-helix protein: building a functional insulin minienhancer
      complex.
AB  - The distal portion of the rat insulin I gene 5'-flanking DNA contains two
      sequence elements, the Far and FLAT elements, that can function in combination,
      but not separately, as a beta-cell-specific transcriptional enhancer. We have
      isolated several cDNAs encoding proteins that bind to the FLAT element. Two of
      these cDNAs, cdx-3 and lmx-1, represent homeo box containing mRNAs with
      restricted patterns of expression. The protein encoded by lmx-1 also contains two
      amino-terminal cysteine/histidine-rich "LIM" domains. Both cdx-3 and lmx-1 can
      activate transcription of a Far/FLAT-linked gene when expressed in a normally non
      insulin-producing fibroblast cell line. Furthermore, in fibroblasts expressing
      transfected beta-cell lmx-1, the addition of the Far-binding, basic helix-loop
      helix protein shPan-1 (the hamster equivalent of human E47) causes a dramatic
      synergistic activation. ShPan-1 causes no activation in fibroblasts expressing
      transfected cdx-3 or the related LIM-homeodomain protein isl-1. Deletion of one
      or both of the LIM domains from the 5' end of the lmx-1 cDNA removes this
      synergistic interaction with shPan-1 without any loss of basal transcriptional
      activation. We conclude that beta-cell lmx-1 functions by binding to the FLAT
      element and interacting through the LIM-containing amino terminus with shPan-1
      bound at the Far element. These proteins form the minimal components for a
      functional minienhancer complex.

PMID- 1358757
TI  - 3'-UTR-dependent deadenylation by the yeast poly(A) nuclease.
AB  - Poly(A) tail removal is the first step in the degradation pathway for some mRNAs.
      The purified poly(A)-binding protein (PAB)-dependent poly(A) nuclease (PAN) from
      yeast removes mRNA poly(A) tails in vitro by a process similar to that observed
      in vivo. The exonucleolytic PAN degrades poly(A) and RNA bound by PAB, and can be
      activated by spermidine to degrade poly(A) in the absence of PAB. The shortening
      of the poly(A) tail down to 10-25 nucleotides and the terminal deadenylation of
      this short adenine tract are kinetically distinct reactions. Poly(A) shortening
      rates are stimulated by the yeast a-mating factor (MFA2) RNA 3' UTR sequence, and
      this occurs by switching PAN from a distributive to a more processive enzyme.
      Terminal deadenylation rates are also stimulated to different extents by various
      RNAs. Inversion of the MFA2 3' UTR sequence completely inhibits the terminal
      deadenylation reaction owing to the presence of an inhibitory element 70
      nucleotides from the poly(A) tail. Other sequence elements inserted at a similar
      distance from the poly(A) tail also interfere with the reaction. These data
      suggest that the two phases of poly(A) degradation can be regulated by mRNA
      sequences, and they provide a mechanistic description of how this regulation
      could occur in vivo.

PMID- 1358759
TI  - Differential regulation of transcription preinitiation complex assembly by
      activator and repressor homeo domain proteins.
AB  - Different eukaryotic transcription factors can act through the same upstream
      binding site to differentially regulate target gene expression, but little is
      known of the underlying mechanisms. Here, we show that Ultrabithorax and even
      skipped homeo domain proteins (UBX and EVE) of Drosophila melanogaster exert
      active and opposite effects on in vitro transcription when bound to a common site
      upstream of a core promoter. Both the activator UBX and the repressor EVE affect
      the extent but not the rate constant of preinitiation complex (preIC) formation.
      Both regulators act early in preIC assembly and are dispensable later. Assembling
      complexes become resistant to regulation by the bound proteins, but activation by
      UBX is restored upon ATP or dATP addition, and regulation by both proteins is
      restored after the addition of all four nucleoside triphosphates and
      transcription initiation. The results establish that upstream activators and
      repressors can function by fundamentally similar mechanisms, by differentially
      regulating an early step in preIC assembly, leading to formation of functionally
      distinct transcription complexes. A subsequent step renders mature complexes
      transiently refractory to activation and repression. Implications for the
      mechanism of transcription complex assembly and turnover and its regulation are
      discussed, including a new role for ATP in turnover.

PMID- 1358760
TI  - Secretion of human blood coagulation factor XIIIa by the yeast Yarrowia
      lipolytica.
AB  - The industrial yeast, Yarrowia lipolytica, secretes high yields of an alkaline
      extracellular protease (AEP), which is synthesized as a preproprotein encoded by
      the XPR2 gene. We investigated the possibility of using this system for the
      secretion of human coagulation factor XIII subunit a (FXIIIa). This protein is
      naturally secreted in the plasma by an unknown, signal peptide-independent
      mechanism and has so far been found to be nonsecretable in yeast. We have
      designed six hybrid genes encoding fusion proteins between increasing portions of
      the AEP preprodomain and the precursor or mature forms of FXIIIa. All constructs
      directed translocation of the FXIIIa precursor into the endoplasmic reticulum.
      Transport of the translocated and core-glycosylated hybrid precursor to the Golgi
      apparatus appeared to be strongly rate limiting, and most of the precursors
      appeared to be partially proteolysed. One of these constructs directed the
      extracellular secretion of a low amount of hyperglycosylated FXIIIa. These
      results indicate that fusion to the yeast AEP signal peptide and dipeptide
      stretch allows FXIIIa to be translocated, albeit inefficiently, through the
      endoplasmic reticulum and to follow a classical secretory transit.

PMID- 1358761
TI  - A rational approach to hypertension treatment in the older patient.

PMID- 1358762
TI  - Effect of potentiation of cholinergic tone by pyridostigmine on the GH response
      to GHRH in elderly men.
AB  - The plasma GH response to GHRH (100 micrograms i.v.) was evaluated either alone
      or after pretreatment with pyridostigmine (120 mg orally 1 h prior to GHRH) in 9
      younger men (age range: 22-39 years) and in 9 healthy elderly men (age range: 63
      77 years). On a different occasion, subjects were tested with pyridostigmine
      alone. Basal concentrations of glucose, cortisol, androgens, estrogens, thyroid
      hormones and GH were similar in all subjects, whereas insulin-like growth factor
      was lower in elderly men. The GH response to GHRH was significantly lower in the
      older (mean peak was 6 times higher than baseline) than in the younger group
      (mean peak was 11.3 times higher than baseline). The pretreatment with
      pyridostigmine induced a striking increase in the GH response to GHRH in the
      younger subjects (mean peak was 26 times higher than baseline), whereas it
      produced only a slight increase in the GHRH-induced GH response in elderly men
      (mean peak was 8.7 times higher than baseline). When pyridostigmine was given
      alone, plasma GH levels rose significantly in both groups; however, the
      pyridostigmine-stimulated GH response was significantly higher in younger (mean
      peak was 6 times higher than baseline) than in older subjects (mean peak was 2.5
      times higher than baseline). These data indicate that the cholinergic stimulatory
      regulation of GH release is reduced in elderly subjects. Since acetylcholine
      inhibits hypothalamic somatostatin release, the reduced cholinergic tone in
      elderly subjects may result in an increased somatostatinergic tone.

PMID- 1358763
TI  - Glutamate metabolism, release, and quantal transmission at central excitatory
      synapses: implications for neural plasticity.
AB  - Glutamate is thought to act as a neurotransmitter at several excitatory synapses
      in the brain. Available knowledge reveals complex intercompartmental dynamics of
      glutamate, which is synthesized, accumulated and released by presynaptic
      elements, activates postsynaptic receptors, and is eventually re-uptaken and
      interconverted to glutamine by the participation of surrounding glial cells. The
      postsynaptic reactions to physiological release of glutamate during
      neurotransmission are considered in relation to the quantal approach, which is
      revealing unsuspected complexity in central synaptic mechanisms. This issue is
      particularly important in view of its implications in the study of long-term
      synaptic modifications.

PMID- 1358764
TI  - Use of cimetidine and other peptic ulcer drugs in Denmark 1977-1990 with analysis
      of the risk of gastric cancer among cimetidine users.
AB  - The prevalence of use of peptic ulcer drugs in the Danish population is described
      at two points in time using registrations of applications for reimbursement. In
      1977-81, the prevalence of use of cimetidine was 0.4% in men and 0.2% in women.
      In 1989-90, the prevalence of use of peptic ulcer drugs was 1.3% in men and 1.2%
      in women. The increase in prevalence was apparent in all age groups, but most
      pronounced at relatively old age. The median age of users increased from 55 years
      in 1977-81 to 63 years in 1989-90. The data indicated that a third of those who
      used peptic ulcer drugs in 1977-81 also used these drugs in 1989-90, conditional
      on surviving this period. The probability of becoming a long term user was
      highest for those who were 50-69 years in 1977-81. The incidence of gastric
      cancer was investigated in the cohort of persons who used cimetidine in 1977-81.
      An excess risk of gastric cancer was apparent in the first years after start of
      cimetidine use. This is thought to reflect a selection bias. Significantly
      increased incidence was also observed in women seven years or longer after start
      of cimetidine use (RR = 4.7; 95% CI: 1.7-10.3). This estimate was, however, based
      on only six cases, and a similar pattern was not observed in men.

PMID- 1358766
TI  - Distribution of somatostatin-immunoreactive nerve fibres in Peyer's patches.
AB  - The distribution of somatostatin-immunoreactive nerve fibres in Peyer's patches
      of the cat was demonstrated by immunocytochemical techniques. A large number of
      immunoreactive nerve fibres was observed in the tela submucosa very close to the
      Peyer's patches. Some immunoreactive nerve cell bodies were also found in this
      layer. The immunoreactive nerve terminals ran around the margin of the follicles
      and only a few nerve fibres were observed in the centre of follicles. Electron
      microscopic investigation showed that these immunoreactive nerve terminals were
      in very close contact with lymphocytes and plasma cells, where no Schwann cell
      sheath was interposed. The gap between the nerve processes and the lymphocytes
      and plasma cells was about 20-200 nm, and occasionally less. These results
      provide morphological evidence consistent with the view that somatostatin has a
      neuroimmunomodulatory action.

PMID- 1358765
TI  - Effects of enteropathogenic Escherichia coli on microvillar membrane proteins
      during organ culture of rabbit intestinal mucosa.
AB  - This study examines the effects of an enteropathogenic Escherichia coli on
      microvillar membrane proteins during organ culture of rabbit ileal explants.
      Explants maintained with enteropathogenic E coli showed brush border effacement
      affecting approximately 50% of enterocytes, and where enteropathogenic E coli
      were closely adherent to the enterocyte surface microvilli were apparently being
      shed as vesicles. The microvillar membrane enzymes alkaline phosphatase,
      aminopeptidase N and alpha-glucosidase were released into the culture medium
      during organ culture, and this process was significantly enhanced by
      enteropathogenic E coli. This increased loss of microvillar membrane enzymes into
      the culture medium was associated with decreased tissue activities of microvillar
      membrane enzymes in enteropathogenic E coli infected ileal explants compared with
      control. For aminopeptidase N in particular, however, total enzyme activities in
      the tissue plus culture medium were increased comparing enteropathogenic E coli
      with control, suggesting that there might be an increase in the rate of synthesis
      of certain microvillar membrane proteins. Reorientating sucrose density gradient
      centrifugation of culture medium showed that alkaline phosphatase, aminopeptidase
      N and alpha-glucosidase were predominantly associated with particles of peak
      modal density 1.19 g/ml in both groups, confirming that enteropathogenic E coli
      accelerate release of microvillar membrane enzymes as vesicles. Analytical
      fractionation of ileal explants showed that enteropathogenic E coli resulted in a
      loss of microvillar membrane enzyme activities from the main brush border peak of
      modal density 1.21 g/ml present in controls. The density of the remaining smaller
      and lighter peak increased from 1.19 g/ml to 1.23 g/ml after homogenisation in
      digitonin, confirming association of these proteins with cholesterol containing
      membranes and not endoplasmic reticulum. These findings suggest that
      enteropathogenic E. coli accelerate the normal shedding of microvillar membrane
      proteins as vesicles, and may stimulate a compensatory increase in microvillar
      membrane protein synthesis.

PMID- 1358767
TI  - Influence of multiple endocrine neoplasia type 1 on gastric endocrine cells in
      patients with the Zollinger-Ellison syndrome.
AB  - The influences of multiple endocrine neoplasia type 1 (MEN 1), hypergastrinaemia,
      age, and sex on gastric endocrine cell densities were studied in 48 patients with
      the Zollinger-Ellison syndrome of either the sporadic type (n = 31) or associated
      with MEN 1 (n = 17). The mean fundic argyrophil cell density was higher in women
      (p < 0.05). It showed no appreciable difference between young and old women but
      it declined with age in men. The mean argyrophil cell density, when adjusted for
      sex, was higher (+48.5%, p = 0.06) in patients with Zollinger-Ellison syndrome
      associated with MEN 1 than in those with sporadic type disease. This measurement
      was not significantly different between the two groups of patients when
      antisecretory treatments were considered. In patients with sporadic type disease,
      fundic argyrophil cells showed a normal pattern (16%) or diffuse (71%) or linear
      (13%) hyperplasia. In patients with MEN 1 diffuse and linear hyperplasia were of
      the same order (53% and 47%). Furthermore, fundic argyrophil endocrine tumours
      developed in five of 17-that is, 29.5% of patients with associated MEN 1 while
      none was seen in patients with sporadic type disease. These tumours showed an
      exclusive or prominent enterochromaffin like cell population. Antral gastrin and
      somatostatin cell densities and fasting serum gastrin concentrations were similar
      in the two groups of patients with Zollinger-Ellison syndrome. Whatever the
      underlying mechanism for carcinoidosis, the risk of developing fundic
      enterochromaffin like cell tumours in Zollinger-Ellison syndrome patients who
      present with MEN 1 is probably higher than was initially estimated and suggests
      that regular follow up of these patients is necessary.

PMID- 1358768
TI  - Postmarketing surveillance of the safety of cimetidine: 10 year mortality report.
AB  - A total of 9928 cimetidine users were identified from prescriptions in four
      centres and followed for 10 years. The 'all-cause' mortality ratio fell from 1.9
      in year 1 to 1.0 in years 8 to 10. Most of the early excess in mortality was
      attributable to cimetidine being given in the late stages of many diseases, often
      to counter adverse gastric effects of other drugs. Specific causes of mortality
      during years 5-10 of the study, were generally unremarkable. Significant
      increases in mortality ratios were apparent, however, for oesophageal cancer
      (years 5-7, 2.3; years 8-10, 1.9); lung cancer (years 5-7, 1.1; years 8-10, 1.7);
      diseases of the oesophagus, stomach, and duodenum (years 5-7, 3.3; years 8-10,
      2.3); and chronic liver disease (years 5-7, 2.4; years 8-10, 3.3). None of these
      increases in mortality seems to be attributable to an adverse effect of
      cimetidine use. Data are also presented for mortality from diseases of the
      nervous system. Eight deaths (of which one was miscoded) were certified as being
      from motor neurone disease, representing a mortality ratio of 2.6 for years 2-10
      of the study which is of borderline statistical significance. This study confirms
      that cimetidine is safe. Mortality from some diseases increased over the study
      period, but selection rather than any adverse effect of the drug is likely to be
      the explanation.

PMID- 1358769
TI  - Inhibition by tiazofurin of inosine 5'-phosphate dehydrogenase (IMP DH) activity
      in extracts of ovarian carcinomas.
AB  - Cancer cells have an increased ability to synthesize GTP (guanosine triphosphate)
      because of increased activity of IMP DH (inosine 5'-phosphate dehydrogenase, EC
      1.1.1.205). Because IMP DH activity is rate limiting for de novo biosynthesis of
      GTP, this enzyme was suggested as a sensitive target for chemotherapy. Tiazofurin
      (2-beta-D-ribofuranosylthiazole-4-carboxamide) is converted in the cells into the
      active metabolite, TAD, (thiazole-4-carboxamide adenine dinucleotide) which
      potently inhibits IMP DH activity. By adding TAD to tissue extracts one can
      determine the extent of inhibition of IMP DH. We applied the IMP DH assay method
      to extracts of normal ovaries (N = 11) and epithelial ovarian carcinomas (N =
      10). The IMP DH activity (mean +/- SE) in ovarian carcinoma was 21.1 +/- 5.8
      which was markedly higher than that observed in normal ovaries (2.9 +/- 0.7
      nmol/hr/mg protein) (P < 0.05%). The inhibition by TAD of IMP DH activity in
      ovarian carcinomas (N = 4) was 81%. The results indicate that IMP DH activity is
      elevated sevenfold in ovarian carcinomas as compared to normal ovary and can be
      inhibited by exposure to tiazofurin (TAD). Similar high IMP DH activity and
      inhibition of the activity by TAD was observed in patients with chronic
      granulocytic leukemia in blast crisis among whom 70 to 80% remissions were
      reported. Since there is increased IMP DH activity in human ovarian carcinomas
      and in OVCAR-5 cells and tiazofurin and TAD inhibit IMP DH activity of these
      cells and the proliferation of human ovarian carcinoma xenografts in the mouse,
      tiazofurin may merit serious consideration for a Phase II trial for patients with
      recurrent/refractory epithelial ovarian carcinoma.

PMID- 1358770
TI  - Gene expression of pyrogenic cytokines in Hodgkin's disease lymph nodes.
AB  - BACKGROUND: Inflammatory cytokines released by either the neoplastic or reactive
      cells in Hodgkin's disease (HD) might mediate its peculiar clinical and
      histopathological features. We investigated by Northern blotting the gene
      expressions of the pyrogenic and inflammation-associated cytokines IL-1 alpha, IL
      1 beta, TNF-alpha, TNF-beta (lymphotoxin) and IL-6 in 14 HD lymph nodes and
      studied their relation to systemic symptoms (B symptoms). METHODS: Two ug of
      poly(A)+RNA from 14 HD lymph nodes (8 from symptomatic and 6 from asymptomatic
      patients, of different histological type and disease stage) were subjected to
      agarose electrophoresis, Northern blotted and hybridized to the various cytokine
      cDNA probes. RESULTS: The inflammatory cytokines were expressed very
      heterogenously in HD, even in lymph nodes with the same histological type and
      with similar stromal inflammatory reactions. IL-1 beta was increased about 2 to
      10 times in 5 of 8 lymph nodes from patients with B symptoms, whereas the other
      cytokines were heterogenously expressed in both symptomatic and asymptomatic
      patients. Statistical analysis on densitometric values demonstrated that the
      difference in IL-1 beta expression between symptomatic and asymptomatic patients
      was significant (p less than 0.02). CONCLUSIONS: These results support the
      hypothesis of increased IL-1 levels in tumoral lymph nodes from symptomatic HD
      patients.

PMID- 1358771
TI  - Carrier detection for prenatal diagnosis of hemophilia A in Italian families.
AB  - BACKGROUND: The results obtained from a comparative analysis between phenotypic
      bioassays as the ratio of factor VIII: C clotting activity to factor VIII: C
      related antigen, and DNA haplotypes from RFLP's TaqI/St14 and BclI/F8A in 12
      hemophilia A (HeA) families are described. METHODS: DNA from HeA patients and
      related at-risk women has been analyzed by Southern blotting with two probes: the
      intragenic F8A and the extragenic St14. Factor VIII: C coagulant activity was
      measured by a one-stage method, and the Factor VIII-related antigen (FVIII: RAg)
      was assayed with bidimensional electrophoresis. Linkage analysis was performed
      with the LINKAGE computer programs; in particular, the risks of carrying HeA were
      calculated using the MLINK program. RESULTS: The observed heterozygosity for the
      flanking marker DXS 52 (TaqI/St14 RFLP) in combination with intragenic BclI/F8A
      polymorphism was 0.94. A statistically significant difference in frequency was
      detected at the DXS 52 locus (allele 4) in comparison with other Caucasian
      populations. Linkage analysis made it possible to combine the plasma bioassay
      values with the DNA marker haplotypes to determine the probability of
      carriership; 22 females at risk were investigated: 4 of them were identified as
      carriers and 18 were excluded. The risk of carrying hemophilia A for some women
      at risk in six families is reported. CONCLUSIONS: This study compares a classic
      method and DNA analysis in genetic counselling for hemophilia A. In some cases
      the two methods may give different results when identifying carriers in at-risk
      families. From these data it is possible to conclude that DNA analysis combined
      with the phenotypic bioassays for carrier detection gives more information that
      the two analyses taken separately.

PMID- 1358772
TI  - High-risk acute lymphoblastic leukemia (ALL): is there an alternative approach
      for increasing the number of cures?

PMID- 1358774
TI  - [Special symposium: Improvement of Therapy of Cardiac Arrhythmias. Class III
      Antiarrhythmic Drugs Focussing on Sotalol and D-Sotalol. Nizza, 17-20 June 1992].

PMID- 1358773
TI  - [Drug therapy of hypertrophic cardiomyopathy].
AB  - INTRODUCTION: Hypertrophy of the myocardium occurring in hypertrophic
      cardiomyopathy (HCM) may affect different locations of the left ventricle. If the
      hypertrophy is sited in the region of the basal septum, obstruction of the left
      ventricular outflow tract (hypertrophic obstructive cardiomyopathy [HOCM])
      occurs. characteristic of left ventricular function in HCM is hypercontractility
      and disordered diastolic relaxation. THERAPEUTIC APPROACHES: In the medical
      treatment of HCM, the calcium antagonists play a leading role. They improve
      relaxation and, through their negative inotropic effect, decrease the
      intraventricular gradient. Although beta-blockers reduce the gradient in outflow
      tract obstruction, they do not improve relaxation. In individual cases the use of
      diuretics and anti-arrhythmic agents may be necessary; in the case of atrial
      fibrillation the use of marcumar is recommended. CAUTIONARY REMARK: In the event
      of dental treatment or invasive diagnostic procedures being necessary,
      prophylactic measures against endocarditis should be initiated.

PMID- 1358775
TI  - Pharmacokinetics of glafenine and glafenic acid in patients with cirrhosis,
      compared to healthy volunteers.
AB  - Pharmacokinetic parameters were evaluated in 12 patients with alcoholic cirrhosis
      and 12 healthy volunteers after a single 400 mg oral dose of glafenine. Glafenine
      (G) and its major active metabolite glafenic acid (GA) were measured at regular
      intervals using a specific high performance liquid chromatographic method.
      Glafenine absorption was significantly delayed in cirrhotic patients (CP) (Tmax =
      2.8 +/- 1.3 hvs 1.5 +/- 0.4 h, p less than 0.01) and was dramatically reduced in
      3 patients. The large hepatic 'first pass' effect observed in healthy volunteers
      was markedly reduced in CP (ratio Cmax GA/Cmax G = 3.6 +/- 2.9 vs 18.9 +/- 9.8, p
      less than 0.001; ratio areas under the curves AUC GA/AUC G = 2.3 +/- 2.3 vs 18.2
      +/- 11.2, p less than 0.001). The elimination half-life of G was prolonged in the
      CP (13.0 +/- 13.1 h vs 1.5 +/- 0.5 h, p less than 0.01). In CP, GA elimination
      half-life was increased (12.0 +/- 13.4 h vs 4.3 +/- 1.3 h, NS) but the difference
      did not reach statistical significance because of large variability. The
      significant rise of G plasma concentrations (Cmax = 2.2 +/- 2.1 mg/L vs 0.7 +/-
      0.2 mg/L, p less than 0.05) and its longer half-life would lead to an
      accumulation if the usual dosage regimen was prescribed for CP and could result
      in nephrotoxicity. On the other hand, lower dosage would be ineffective because
      only GA is active and nephrotoxic. Hence, G should be given with great caution to
      CP.

PMID- 1358777
TI  - New Aspects of the Physiology and Pathology of the Luteal Phase. 3rd Tokyo
      Conference on Reproductive Physiology. Tokyo, Japan, August 24, 1991.

PMID- 1358776
TI  - Effect of nicotinic acid on plasma glucose concentration in normal individuals.
AB  - In order to assess the ability of nicotinic acid to decrease plasma glucose
      concentration, normal individuals were given continuous four hour infusions of
      either nicotinic acid (NA), somatostatin (SRIF), NA + SRIF, or 0.9% NaCl
      (Saline). Plasma non-esterified fatty acid (NEFA) concentration decreased to
      about one-fourth of the basal value in response to either NA or NA + SRIF,
      associated with statistically significant decreases in plasma glucose
      concentration. The ability of NA and NA + SRIF to decrease plasma glucose
      concentration was seen despite the fact that plasma insulin concentrations also
      fell significantly during both infusions. Although plasma glucose concentration
      fell significantly in response to both NA and NA + SRIF, the effect of NA + SRIF
      was approximately twice as great as that seen with NA alone. The augmented
      hypoglycaemic effect of NA + SRIF as compared to NA alone was associated with a
      concomitant fall in plasma glucagon concentration. In contrast, plasma glucose
      concentration did not change following Saline, and was actually higher than
      baseline after the infusion of SRIF alone. These results provide evidence that NA
      can lower plasma glucose concentration in normal volunteers, and suggests that
      this is mediated by the NA-associated decrease in plasma NEFA concentration.

PMID- 1358778
TI  - International Symposium on Endocrinology and Development: Basic and Clinical
      Aspects. Athens, October 12-14, 1990.

PMID- 1358779
TI  - Estimated central blood volume in cirrhosis: relationship to sympathetic nervous
      activity, beta-adrenergic blockade and atrial natriuretic factor.
AB  - The estimated central blood volume (i.e., blood volume in the heart cavities,
      lungs and central arterial tree) was determined by multiplying cardiac output by
      circulatory mean transit time in 19 patients with cirrhosis and compared with
      sympathetic nervous activity and circulating level of atrial natriuretic factor.
      Arterial norepinephrine level, an index of overall sympathetic nervous activity
      (3.08 nmol/L in patients vs. 1.36 nmol/L in controls; p < 0.01) was negatively
      correlated (r = -0.54, p < 0.01) with estimated central blood volume (mean = 23
      ml/kg in patients vs. 27 ml/kg in controls; p < 0.05). Similarly, renal venous
      norepinephrine level (an index of renal sympathetic tone; 4.26 nmol/L in patients
      vs. 1.78 nmol/L in controls; p < 0.01) was inversely correlated with estimated
      central blood volume (r = -0.53, n = 18, p < 0.02). No significant correlation
      could be established between arterial atrial natriuretic factor level (8.9 pmol/L
      in patients vs. 9.6 pmol/L in controls; not significant) and estimated central
      blood volume. Hemodynamic values were subsequently modified with oral propranolol
      (80 mg). During beta-adrenergic blockade, the mean estimated central blood volume
      was not altered significantly, except in six patients who exhibited decreases in
      mean arterial blood pressure (85 to 69 mm Hg; n = 6) and decreases in mean
      estimated central blood volume (23.2 to 20.6 ml/kg; n = 6, p < 0.05). Slight
      increases were observed in mean right atrial pressure (2.2 to 3.7 mm Hg; n = 14,
      p < 0.05); this change was positively correlated with the change in estimated
      central blood volume (r = 0.44, n = 14, p = 0.06).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1358780
TI  - Treatment of schizophrenia: current practice and future promise.
AB  - Studies published since 1988 describing the treatment of schizophrenia are
      reviewed. Antipsychotic agents play a dominant role in treatment, but, except for
      clozapine, no one drug has been proved more effective than any other. Ineffective
      medication and medication noncompliance may contribute to apparent treatment
      resistance. Used in conjunction with drug treatment, supportive psychotherapy
      that incorporates social skills training appears to be useful. Environmental
      interventions such as supervised housing and work with families appear to help
      patients function better in the community and avoid relapse. Trials of new
      antipsychotic agents and improved understanding of the neurochemistry of
      schizophrenia offer hope that improved therapies will become available.

PMID- 1358781
TI  - Expression of p53 in human esophageal carcinoma: an immunohistochemical study
      with correlation to proliferating cell nuclear antigen expression.
AB  - Immunolocalization of the nuclear protein p53 tumor suppressor gene product is
      considered to be one of the best methods of detecting a mutated form of p53. We
      have studied p53 immunohistochemically by using monoclonal antibody pAb1801 in 15
      cases of esophageal squamous cell carcinoma. Immunoreactive p53 was observed in
      the nuclei of tumor cells in 4% paraformaldehyde-fixed, frozen sections (12 of
      15) and paraffin-embedded sections (11 of 15), but not in routinely processed
      (10% formalin-fixed) specimens. p53 expression was closely correlated with the
      malignant phenotype, including dysplasia. p53 was not observed in histologically
      normal mucosa, except in three cases in which scattered immunoreactivity was
      observed in parabasal and basal cells. Immunostaining of ki67 and proliferating
      cellular nuclear antigen on adjacent tissue sections revealed that p53 expression
      was strongly correlated with ki67 and proliferating cellular nuclear antigen in
      carcinoma and dysplastic cells, but not in normal mucosa, suggesting involvement
      of the mutated form of p53 in the cell cycle of malignant cells.
      Immunohistochemical patterns of p53 were not related significantly to
      clinicopathologic parameters in the cases examined. Therefore, p53 expression was
      strongly associated with the proliferation of carcinoma cells but not with that
      of normal cells in esophageal carcinoma.

PMID- 1358782
TI  - No association between RFLPs at the porphobilinogen deaminase gene and
      schizophrenia.
AB  - An association study of restriction fragment length polymorphisms (RFLPs) in the
      porphobilinogen deaminase (PBGD) gene and schizophrenia was conducted. RFLPs
      detected by MspI, PstI, ApaLI and BstNI in intron 1 of the gene were studied in
      49 patients and 79 controls. There were no significant differences between the
      groups in allele frequencies, genotype counts or haplotype distribution.

PMID- 1358783
TI  - CpG hotspot causes second mutation in codon 408 of the phenylalanine hydroxylase
      gene.
AB  - A new mutation has been identified in exon 12 of the gene encoding phenylalanine
      hydroxylase at codon 408. The single base change from guanine to adenine changes
      the amino acid arginine to glutamine; thus, the mutation is defined as R408Q.
      This codon is the site of a mutation known to causes phenylketonuria. Both these
      mutations are located at the same CpG site.

PMID- 1358784
TI  - Haplotype distribution and mutations at the PAH locus in Croatia.
AB  - Restriction fragment length polymorphism (RFLP) haplotypes and mutations at the
      phenylalanine hydroxylase (PAH) locus have been studied in 25 unrelated families
      from Croatia. The results of RFLP analysis demonstrated that 80% of the mutant
      alleles were associated with three haplotypes (1, 2 and 4). Eight mutations were
      detected on the background of six mutant haplotypes, comprising 68% of
      phenylketonuria (PKU) alleles in Croatia. The mutation in codon 408 was most
      frequent, as was the haplotype 2 allele with which it was associated. These data
      are in accordance with formerly published population genetic analyses at the PAH
      locus, and with studies revealing the molecular basis of the phenotypic
      heterogeneity of PKU. The codon 281 mutation was more frequent in Croatia than
      previously observed in other populations.

PMID- 1358785
TI  - Transthyretin Pro 36 associated with familial amyloidotic polyneuropathy in an
      Ashkenazic Jewish kindred.
AB  - Mutations in the serum protein transthyretin (TTR) cause amyloidosis involving
      the peripheral nerves, heart, and other organs. In Ashkenazic Jews, the only TTR
      variant described to date has been TTR Ile 33. We have studied DNA from another
      Ashkenazic Jewish kindred with familial amyloidotic polyneuropathy. Single-strand
      conformation polymorphism analysis, DNA sequencing, and restriction analysis
      indicated that this kindred has the TTR Pro 36 variant, previously described only
      in a Greek kindred.

PMID- 1358786
TI  - Linkage study in a large pedigree with Stickler syndrome: exclusion of COL2A1 as
      the mutant gene.
AB  - A three generation family with Stickler syndrome is reported. Affected patients
      exhibited myopia with frequent retinal detachment or glaucoma. Most of them had
      characteristic facial dysmorphism, the Pierre-Robin sequence being observed in
      four individuals. Neonatal radiological signs of the Weissenbacher-Zweymuller
      syndrome were also noticed but early arthopathy was not reported in adults.
      Restriction fragment length polymorphism studies with the type II collagen gene
      (COL2A1) showed a recombination event between the disease locus and COL2A1, thus
      excluding collagen type II as the candidate gene. Although the calculation of the
      likelihood of genetic heterogeneity versus homogeneity based on 10 families was
      not statistically significant, we suggest that a second locus is probably
      involved in this highly variable syndrome.

PMID- 1358787
TI  - Molecular and genetic characterization and physical mapping of 11 new markers
      detecting multiallele restriction fragment length polymorphisms on the short arm
      of human chromosome 3.
AB  - Genetic markers with high degrees of polymorphisms are of vital importance in the
      construction of high resolution (2-4 cM) linkage maps of human chromosomes as
      specified in the short-term goals of the Human Genome Initiative. In this paper,
      we report on molecular and genetic characterization and physical localization of
      11 new multiallele restriction fragment length polymorphism markers on human
      chromosome 3p. Ten of these represent three- and four-allele polymorphisms of the
      base substitution type probably at two adjacent restriction sites. One has been
      identified as a novel mini-satellite sequence comprising a variable copy number
      tandem repeat array of a G/T-rich 79-bp sequence. This collection of multiallele
      polymorphic (PIC values: 0.40-0.60) markers should prove valuable and increase
      the resolution power of the available chromosome 3p genetic markers.

PMID- 1358789
TI  - Molecular basis for nonphenylketonuria hyperphenylalaninemia.
AB  - Nonphenylketonuria hyperphenylalaninemia (non-PKU HPA) is defined as
      phenylalanine hydroxylase (PAH) deficiency with blood phenylalanine levels below
      600 mumol/liter (i.e., within the therapeutic range) on a normal dietary intake.
      Haplotype analysis at the PAH locus was performed in 17 Danish families with non
      PKU HPA, revealing compound heterozygosity in all individuals. By allele-specific
      oligonucleotide (ASO) probing for common PKU mutations we found 12 of 17 non-PKU
      HPA children with a PKU allele on one chromosome. To identify molecular lesions
      in the second allele, individual exons were amplified by polymerase chain
      reaction and screened for mutations by single-strand conformation polymorphism.
      Two new missense mutations were identified. Three children had inherited a G-to-A
      transition at codon 415 in exon 12 of the PAH gene, resulting in the substitution
      of asparagine for aspartate, whereas one child possessed an A-to-G transition at
      codon 306 in exon 9, causing the replacement of an isoleucine by a valine in the
      enzyme. It is further demonstrated that the identified mutations have less impact
      on the heterozygote's ability to hydroxylate phenylalanine to tyrosine compared
      to the parents carrying a PKU mutation. The combined effect on PAH activity
      explains the non-PKU HPA phenotype of the child. The present observations that
      PKU mutations in combination with other mutations result in the non-PKU HPA
      phenotype and that particular mutation-restriction fragment length polymorphism
      haplotype combinations are associated with this phenotype offer the possibility
      of distinguishing PKU patients from non-PKU individuals by means of molecular
      analysis of the hyperphenylalaninemic neonate and, consequently, of determining
      whether a newborn child requires dietary treatment.

PMID- 1358788
TI  - Analysis of the 5' flanking sequence of the G gamma globin gene by denaturing
      gradient gel electrophoresis confirms the heterogeneity of the Bantu beta S
      haplotype.
AB  - The GC-->TT polymorphism recently described at positions -1106 and -1105 in the
      5' flanking region of the G gamma globin gene for the Bantu beta S haplotype was
      analysed by denaturing gradient gel electrophoresis. We studied 108 beta S
      chromosome and 122 beta A chromosomes. The TT sequence was found as follows: in
      all of 80 chromosomes bearing the Bantu beta S haplotype with the 6-bp deletion 
      400 nt from the G gamma gene in 3 out of 5 Bantu beta S chromosomes without the
      deletion, in 1 out of 122 beta A chromosomes from different ethnic origins but in
      none of 23 beta S chromosomes bearing the Senegal, Benin or Cameroon haplotypes.
      These results confirm the heterogeneity of the Bantu beta S haplotype and allow a
      tentative evolutionary sequence for the different alleles at this locus to be
      presented.

PMID- 1358790
TI  - Evidence implicating heterozygous deletion of chromosome 7 in the pathogenesis of
      familial leukemia associated with monosomy 7.
AB  - Complete or partial monosomy 7 is a recurring cytogenetic abnormality in acute
      myelogenous leukemia (AML) and myeloproliferative syndromes (MPS) and is
      particularly common in patients with Fanconi's anemia and in secondary AML. A
      familial form of monosomy 7 has been recognized in which two or more siblings
      develop MPS or AML before age 20. We tested the hypothesis that a recessive
      cancer susceptibility locus on chromosome 7 was important in the pathogenesis of
      leukemia in familial monosomy 7 by determining the parental origins of the
      chromosome 7 retained in the bone marrows of three pairs of affected siblings. We
      found no overlapping region where all three pairs retained DNA derived from the
      same paternal or maternal chromosome. These data suggest that inactivation of a
      single allele of a putative tumor-suppressor gene may be sufficient to contribute
      to leukemic transformation in familial monosomy 7.

PMID- 1358791
TI  - Somatic cell mapping, polymorphism, and linkage analysis of bovine prolactin
      related proteins and placental lactogen.
AB  - The bovine prolactin gene family includes novel members expressed in the fetal
      placenta that are distinct from placental lactogen. In this study, we
      investigated the genetic organization of four members of this gene family (PRP1,
      PRP3, PRP6, and PRP10) as well as placental lactogen (PL). Using a bovine-rodent
      hybrid somatic cell panel, all five genes were assigned to bovine chromosome 23,
      which contains prolactin and the major histocompatibility group (BOLA).
      Restriction fragment length polymorphisms were detected by all probes in breeding
      populations with the restriction enzyme MspI, whereas no polymorphisms were
      detected with BamHI. EcoRI, HindIII, TaqI, and PstI produced polymorphic
      fragments with some but not all of the probes tested. A PRP10 polymorphism, which
      is apparently the result of a insertion/deletion event, detected polymorphism
      frequency differences between Bos indicus and Bos taurus. No recombinational
      events were observed with these probes and prolactin using linkage analysis
      involving 91 American Holsteins. The bovine prolactin gene family was
      incorporated into a linkage group containing CYP21. Our studies demonstrate that
      members of the bovine prolactin gene family have a close physical association
      with each other, and all members demonstrate genetic variability in the breeding
      population.

PMID- 1358793
TI  - Generation of 19 STS markers that can be anchored at specific sites on human
      chromosome 21.
AB  - Sequence-tagged sites (STSs) are short stretches of DNA that can be specifically
      detected by the polymerase chain reaction (PCR) and can be used to construct long
      range physical maps of chromosomal DNA. These STSs can be detected by PCR assays
      developed by reference to data obtained from the sequencing of restriction
      fragment length polymorphism-DNA markers for chromosome 21, which were derived
      from recombinant lamba-phage and plasmid clones made from DNA of a human-hamster
      hybrid cell line. In this report, we describe the generation of 19 new STSs that
      are specific for human chromosome 21.

PMID- 1358792
TI  - Cloning of the human cholesterol 7 alpha-hydroxylase gene (CYP7) and localization
      to chromosome 8q11-q12.
AB  - Cholesterol 7 alpha-hydroxylase (7 alpha-hydroxylase) is a microsomal cytochrome
      P450 that catalyzes the first step in bile acid synthesis. In this paper, we
      describe the cloning, characterization, and chromosomal mapping of the human 7
      alpha-hydroxylase gene (CYP7). The gene spans 10 kb and contains six exons and
      five introns. The exon-intron boundaries are completely conserved between the
      human and rat genes. Sequencing of the 5' flanking region revealed consensus
      recognition sequences for a number of liver-specific transcription factors. The
      human CYP7 gene was mapped to chromosome 8q11-q12 using both mouse-human somatic
      cell hybrids and in situ chromosomal hybridization studies. A total of four
      single-stranded conformation-dependent DNA polymorphisms and an Alu sequence
      related polymorphism were identified. Of the individuals analyzed, 80% were
      heterozygous for at least one of these five polymorphisms. The localization and
      characterization of the human 7 alpha-hydroxylase gene, as well as the
      identification of polymorphisms, provide the molecular tools necessary to
      investigate the role of this gene in disorders of cholesterol and bile acid
      metabolism.

PMID- 1358794
TI  - Localization of insulin-2 (Ins-2) and the obesity mutant tubby (tub) to distinct
      regions of mouse chromosome 7.
AB  - A DNA mapping panel derived from an interspecific backcross was used to position
      the mouse insulin-2 locus (Ins-2) on Chromosome 7, near H19 (0/114 recombinants)
      and Th (1/114 recombinants). Ins-2 is part of a human-mouse conserved linkage
      group that includes Th, H19, and Igf-2. Analysis of segregation in the F2
      generation from the cross C57BL/6J-tub/tub x CAST/Ei demonstrated that Ins-2 and
      the obesity mutant tubby (tub) are distinct loci, thus eliminating Ins-2 as a
      candidate gene for tub. These results also refine the estimated genetic distance
      between tub and Hbb to 2.4 +/- 1.4 cM. The predicted location for a human homolog
      of tubby is HSA 11p15.

PMID- 1358795
TI  - A linkage map of mouse chromosome 19: definition of comparative mapping
      relationships with human chromosomes 10 and 11 including the MEN1 locus.
AB  - A linkage map of mouse Chromosome (Chr) 19 was constructed using an interspecific
      cross and markers defined by restriction fragment length variants. The map
      includes 20 markers, 9 of which had not been mapped previously in the mouse. The
      data further defined the relationship between genes on mouse Chr 19 and those on
      the long arm of human Chr 10 and the pericentric region of the long arm of human
      Chr 11. The comparative mapping analysis suggests that the proximal segment of
      mouse Chr 19 may contain the MEN1 locus and that the current study has identified
      additional genes that may be useful for positional cloning of this putative tumor
      suppressor gene.

PMID- 1358796
TI  - Identification and mapping of six microdissected genomic DNA probes to the
      proximal region of mouse chromosome 1.
AB  - Six independent DNA probes, lambda Mm1C-150, lambda Mm1C-153, lambda Mm1C-156,
      lambda Mm1C-162, lambda Mm1C-163, and lambda Mm1C-165, have been isolated from a
      library of microdissected fragments from mouse chromosome 1, spanning cytogenetic
      bands C2 to C5. These DNA probes have been mapped by restriction fragment length
      polymorphism analysis with respect to 12 marker loci previously assigned to this
      portion of mouse chromosome 1, in a panel of 251 segregating Mus spretus x
      C57BL/6J interspecific backcross mice. The gene order and intergene distances
      were determined by segregation analysis to be centromere- lambda Mm1C-162-11.1 cM
      Col3a1-8.8 cM-Len-2-2.6 cM-lambda Mm1C-163-1.6 cM-Fn-1-1.6 cM-Tp-1-0.8 cM-lambda
      Mm1C-165/Vil-0.4 cM-Inha-2.8 cM-lambda Mm1C-153-2.4 cM-lambda Mm1C-156-1.2 cM-Pax
      3-5.6 cM-Akp-3-0.8 cM-Acrg-2.0 cM-Sag-0.5 cM-Col6a3-1.8 cM-lambda Mm1C-150-15.4
      cM-Ren1,2. Four of these probes map within a chromosome 1 segment that is
      homologous to human chromosome 2q. Southern blotting analyses indicate that one
      of these anonymous probes, lambda Mm1C-165, detects DNA fragments highly
      conserved across species. These novel polymorphic probes should prove useful for
      linkage and physical mapping of this chromosomal region.

PMID- 1358797
TI  - Evolution of a highly polymorphic human cytochrome P450 gene cluster: CYP2D6.
AB  - The CYP2D gene cluster on human chromosome 22 containing the functional
      cytochrome P450 gene CYP2D6 and two or three highly homologous pseudogenes is
      involved in a clinically important variation in the inactivation of drugs and
      environmental chemicals. Several mutant haplotypes of CYP2D6 have been identified
      by restriction analysis and by PCR-based allele-specific amplification. To
      understand the evolutionary sequence of mutational events as well as recently
      discovered interracial differences, we analyzed the arrangement of the CYP2D
      haplotype containing a common mutant allele of CYP2D6 associated with a XbaI 44
      kb fragment. This haplotype contains four CYP2D genes instead of three.
      Comparison of the sequences of these genes with those of previously characterized
      haplotypes suggests that an early point mutation was followed by a crossover and
      a gene conversion event, the latter found preferentially in Caucasians. These
      data are consistent with the rapid evolution of this locus during "plant-animal
      warfare" with practical consequences for present-day defense of the organism
      against environmental adversity.

PMID- 1358798
TI  - Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated
      subunits to chromosomes 3 and 5.
AB  - IL12 (formerly NKSF or CLMF) is a unique cytokine composed of two unrelated
      disulfide-linked subunits. The larger 40-kDa subunit (p40) is a member of the
      cytokine receptor family, and the smaller 35-kDa subunit (p35) is related to IL6
      and GCSF. The chromosomal localization of these two subunits was determined by
      PCR analysis of DNA from rodent-human hybrids. More refined mapping was obtained
      by PCR analysis of hybrids containing translocation chromosomes and for p40, by
      analysis of radiation hybrids. The subunits map to different chromosomes: p40
      (IL12B) to 5q31-q33 and p35 (IL12A) to 3p12-3q13.2.

PMID- 1358799
TI  - Mapping of the regulatory subunits RI beta and RII beta of cAMP-dependent protein
      kinase genes on human chromosome 7.
AB  - The genes encoding the regulatory subunits RI beta (locus PRKAR1B) and RII beta
      (locus PRKAR2B) of human cAMP-dependent protein kinase have been mapped in the
      basic CEPH (Centre d'Etude du Polymorphisme Humain) family panel of 40 families
      to chromosome 7p and 7q, respectively, using the enzymes HindIII and BanII
      recognizing the corresponding restriction fragment length polymorphisms (RFLPs).
      Previous data from the CEPH database and our present RFLP data were used to
      construct a six-point local framework map including PRKAR1B and a seven-point
      framework map including PRKAR2B. The analysis placed PRKAR1B as the most distal
      of the hitherto mapped 7p marker loci and resulted in an unequivocal order of
      pter-PRKAR1B-D7S21-D7S108-D7S17-D7S149- D7S62-cen, with a significantly higher
      rate of male than female recombination between PRKAR1B and D7S21. The 7q
      regulatory gene locus, PRKAR2B, could also be placed in an unambigous order with
      regard to the existing CEPH database 7q marker loci, the resulting order being
      cen-D7S371-(COL1A2,D7S79)-PRKAR2B-MET-D7S87++ +-TCRB-qter. Furthermore, in situ
      hybridization to metaphase chromosomes physically mapped PRKAR2B to band q22 on
      chromosome 7.

PMID- 1358801
TI  - The accuracy of DNA sequences: estimating sequence quality.
AB  - In this paper we describe a method for the statistical reconstruction of a large
      DNA sequence from a set of sequenced fragments. We assume that the fragments have
      been assembled and address the problem of determining the degree to which the
      reconstructed sequence is free from errors, i.e., its accuracy. A consensus
      distribution is derived from the assembled fragment configuration based upon the
      rates of sequencing errors in the individual fragments. The consensus
      distribution can be used to find a minimally redundant consensus sequence that
      meets a prespecified confidence level, either base by base or across any region
      of the sequence. A likelihood-based procedure for the estimation of the
      sequencing error rates, which utilizes an iterative EM algorithm, is described.
      Prior knowledge of the error rates is easily incorporated into the estimation
      procedure. The methods are applied to a set of assembled sequence fragments from
      the human G6PD locus. We close the paper with a brief discussion of the relevance
      and practical implications of this work.

PMID- 1358800
TI  - Methylation of the DXS255 hypervariable locus 5' CCGG site may be affected by
      factors other than X-chromosome activation status.
AB  - Differences in the methylation status of certain cytosine residues between active
      and inactive X chromosomes can be used to determine X-inactivation in females
      heterozygous for X-linked restriction fragment length polymorphisms. We have
      studied methylation patterns in 105 females heterozygous at the DXS255 locus by
      Southern blotting of PstI and MspI or HpaII double digests and hybridization with
      the probe M27B. Unequivocal patterns of unilateral or bilateral X-inactivation
      were obtained in 15/64 and 49/64 cases, respectively. In the remaining 41 cases
      the results were unclear due to the absence of HpaII digestion of one or both
      PstI fragments. In 7 samples an unequivocal digestion pattern was demonstrated on
      repeat analysis, suggesting that the initial ambiguous pattern was due to
      incomplete HpaII digestion. In certain individuals, methylation at the 5' CCGG
      DXS255 locus may be affected by factors other than X-inactivation, making
      analysis of clonality with the M27B probe impossible. These individuals should be
      clearly identified in studies of clonality.

PMID- 1358802
TI  - The gene for a novel epidermal antigen maps near the neurofibromatosis 1 gene.
AB  - Recently the M17S1 gene, encoding an epidermal antigen thought to play a role in
      cell adhesion, was mapped to chromosome bands 17q11-q12, placing it in the
      vicinity of the gene for the genetic disorder neurofibromatosis 1 (NF1). The
      pleomorphic cutaneous lesions of NF1 and the precedent for other genes being
      embedded within the NF1 gene prompted us to investigate whether the M17S1 gene
      mapped near, or within, the NF1 gene. Genetic linkage analyses revealed that
      M17S1 was tightly linked to NF1 and mapped within the interval bounded by D17S58
      and D17S54. Physical mapping of an M17S1 cDNA on somatic cell hybrids, yeast
      artificial chromosomes, and an NF1 patient with a deletion involving an entire
      NF1 allele demonstrated that M17S1 is located at least 180 kb centromeric to the
      NF1 gene. The distance between the genes suggests that M17S1 is unlikely to
      contribute to the NF1 phenotype since a gross chromosomal rearrangement would be
      required to disrupt expression of both genes.

PMID- 1358803
TI  - Gene order and genetic distance of 13 loci spanning murine chromosome 15.
AB  - Thirteen genetic loci spanning murine chromosome 15 from 15A2 (Mlvi-2) to 15F2-3
      (Gdc-1) have been mapped. The genetic distance extends to 55.4 cM. Among 151
      animals, only 1 animal with a double cross-over was found. The linear order is
      unambiguous, with the exception of the distal end on 15F1-3. Our analysis favors
      the order cen-Ela-1/Hox-3-Wnt-1-Gdc-1-ter. This ordering makes necessary the
      introduction of three tightly spaced double recombination events around and
      within the Hox-3 locus. Alternatively, Hox-3 may be most distal, and several
      double recombinations at the telomere lead to map expansion. Despite the unequal
      distribution along chromosome 15 of G-versus R-bands, a comparison of distances
      determined by physical and genetic mapping does not indicate an overt difference
      in distance between both mapping techniques.

PMID- 1358804
TI  - Genetic mapping of tandemly repeated telomeric DNA sequences in tomato
      (Lycopersicon esculentum).
AB  - A telomere-associated tandemly repeated DNA sequence of tomato, TGR I, has been
      used to map telomeres on the tomato RFLP linkage map. Mapping was performed by
      monitoring the segregation of entire arrays of TGR I from a segregating F2
      population using pulsed-field gel electrophoresis (PFGE). With this strategy,
      four telomeres have been mapped to the ends of the short arm of chromosomes 9 and
      12 and the long arms of chromosomes 5 and 11, using a saturated RFLP map of
      tomato containing approximately 1000 RFLP markers. In all four cases, the TGR I
      locus maps to the end of the chromosome, and the distance between the most distal
      single-copy RFLP marker and the telomeric TGR I locus was between 1.6 and 9.6 cM.
      This indicates that the region close to the telomeres does not show an excessive
      rate of recombination compared to other regions of the genome and that the RFLP
      map of tomato is essentially complete and covers the entire genome for all
      practical purposes. Additionally, the mapping technique presented here should be
      generally applicable to the mapping of other tandemly repeated DNA sequences.

PMID- 1358806
TI  - Assignment of the gene for acetylcholinesterase to distal mouse chromosome 5.
AB  - Characterization of genomic clones encoding mouse acetylcholinesterase enabled us
      to identify a restriction fragment length polymorphism that distinguishes between
      the progenitor strains for the recombinant inbred strain sets AKXD and BXD. The
      strain distribution pattern for this polymorphism indicates that Ache is located
      on distal mouse chromosome 5.

PMID- 1358805
TI  - Arrangement and localization of the human GM-CSF receptor alpha chain gene CSF2RA
      within the X-Y pseudoautosomal region.
AB  - The gene encoding one subunit of the receptor for the hemopoietic growth factor,
      GM-CSF, has been previously localized to the short arm of the human sex
      chromosomes. By pulsed-field gel electrophoresis, the precise localization of
      this gene, CSF2RA, within the pseudoautosomal region has been determined. The
      gene is located 1180 to 1300 kb from the telomere, in close proximity to the CpG
      island B5. The CSF2RA gene spans at least 45 kb, and a representation of most of
      the gene on three overlapping cosmid clones has been obtained. The exon(s)
      encoding the first 35 bp of cDNA sequence lies outside these cosmids. The CSF2RA
      gene is characterized by abundant hypervariable sequences, and a number of
      informative restriction fragment length polymorphisms have been defined.

PMID- 1358807
TI  - Genetic heterogeneity in X-linked amelogenesis imperfecta.
AB  - The AMELX gene located at Xp22.1-p22.3 encodes for the enamel protein amelogenin
      and has been implicated as the gene responsible for the inherited dental
      abnormality X-linked amelogenesis imperfecta (XAI). Three families with XAI have
      been investigated using polymorphic DNA markers flanking the position of AMELX.
      Using two-point linkage analysis, linkage was established between XAI and several
      of these markers in two families, with a combined lod score of 6.05 for DXS16 at
      theta = 0.04. This supports the involvement of AMELX, located close to DXS16, in
      the XAI disease process (AIH1) in those families. Using multipoint linkage
      analysis, the combined maximum lod score for these two families was 7.30 for a
      location of AIH1 at 2 cM distal to DXS16. The support interval around this
      location extended about 8 cM proximal to DXS92, and the AIH1 location could not
      be precisely defined by multipoint mapping. Study of recombination events
      indicated that AIH1 lies in the interval between DXS143 and DXS85. There was
      significant evidence against linkage to this region in the third family,
      indicating locus heterogeneity in XAI. Further analysis with markers on the long
      arm of the X chromosome showed evidence of linkage to DXS144E and F9 with no
      recombination with either of these markers. Two-point analysis gave a peak lod
      score at DXS144E with a maximum lod score of 2.83 at theta = 0, with a peak lod
      score in multipoint linkage analysis of 2.84 at theta = 0. The support interval
      extended 9 cM proximal to DXS144E and 14 cM distal to F9.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1358808
TI  - Mapping of the mouse Rxr loci encoding nuclear retinoid X receptors RXR alpha,
      RXR beta, and RXR gamma.
AB  - Recently, a novel subgroup of nuclear hormone receptors called RXRs implicated
      for retinoid-mediated gene regulation have been identified. RXRs appear to
      interact with many other nuclear hormone receptors and modulate their functions.
      We have mapped genetic loci Rxra, Rxrb, and Rxrg encoding three RXR subtypes, RXR
      alpha, RXR beta, and RXR gamma, respectively, using interspecific backcross mice.
      None of the Rxr loci cosegregated with each other or with the retinoic acid
      receptor loci (Rar) mapped previously. Rxra mapped to Chr 2 near the centromere,
      Rxrb mapped to the H-2 region of Chr 17, and Rxrg was tightly linked to the Pbx
      gene on distal Chr 1. These results underscore that RXR genes are dispersed in
      the genome.

PMID- 1358809
TI  - Genetic map of nine polymorphic loci comprising a single linkage group on rat
      chromosome 10: evidence for linkage conservation with human chromosome 17 and
      mouse chromosome 11.
AB  - Seven genes and two anonymous markers were mapped to a single linkage group on
      rat chromosome 10 using progeny of an F2 intercross of Fischer (F344/N) and Lewis
      (LEW/N) inbred rats. Two genes, the neu oncogene or cellular homologue of the
      viral oncogene erbb2 (ERBB2) and growth hormone (GH) were mapped by Southern blot
      analysis of restriction fragment length polymorphisms. Five genes, embryonic
      skeletal myosin heavy chain (MYH3), androgen binding protein/sex hormone binding
      globulin (SHBG), asialoglycoprotein receptor (hepatic lectin)-1 (ASGR1), ATP
      citrate lysase (CLATP), and pancreatic polypeptide (PPY), and two anonymous
      markers, F16F2 and F10F1, were mapped using PCR amplification techniques. The PCR
      typable polymorphic markers for the five genes were also highly polymorphic in 10
      other inbred rat strains (SHR/N, WKY/N, MNR/N, MR/N, LOU/MN, BN/SsN, BUF/N,
      WBB1/N, WBB2/N, and ACI/N). These markers should be useful in genetic analysis of
      traits described in inbred rat strains, as well as in genetic monitoring of such
      strains. The loci in this linkage group covered 50 cM of rat chromosome 10 with
      the following order: MYH3, SHBG/ASGR1 (no recombinants detected), F16F2, ERBB2,
      CLATP, PPY, GH, and F10F1. Comparative gene mapping analysis indicated that this
      region of rat chromosome 10 exhibits linkage conservation with regions of human
      chromosome 17 and mouse chromosome 11.

PMID- 1358810
TI  - Pax1, a member of the paired box-containing class of developmental control genes,
      is mapped to human chromosome 20p11.2 by in situ hybridization (ISH and FISH).
AB  - Pax-1, a member of a murine multigene family, belongs to the paired box
      containing class of developmental control genes first identified in Drosophila.
      The Pax-1 gene encodes a sequence-specific DNA-binding protein with
      transcriptional activating properties and has been found to be mutated in the
      autosomal recessive mutation undulated (un) on mouse chromosome 2 with vertebral
      anomalies along the entire rostrocaudal axis. By radioactive in situ
      hybridization (ISH) using a fragment from the murine Pax-1 paired box that is
      almost identical to the respective sequences from the cognate human gene HuP48
      and fluorescence in situ hybridization (FISH) using a complete mouse Pax-1 cDNA,
      we have assigned the human homologue of murine Pax-1, the PAX1 locus, to
      chromosome 20p. The map position of PAX1 after FISH (FL-pter value of 0.34 +/-
      0.04) corresponds to band p11.2. These results confirm the exceptional homology
      between human chromosome 20 and the distal segment of mouse chromosome 2,
      extending from bands F to G, and add PAX1 to the group of genes on 20p like PTPA,
      PRNP, SCG1, BMP2A, which are located in proximity on both chromosomes.

PMID- 1358811
TI  - Mapping Creb-1 to chromosome 1 in the mouse.
AB  - The gene CREB1 encoding the cyclic AMP response element DNA binding protein was
      previously assigned to human 2q32.3-q34. In this study, a panel of 207 backcross
      mice made between C57BL/10ScSn (=B10) females and (B10 x B10.L-Lsh)F1 males were
      used to map Creb-1 with respect to Cryg and Lsh/Vil on mouse chromosome 1. A
      reverse-transcribed, polymerase chain reaction-amplified cDNA probe covering bp
      39 to 554 of the human sequence identified restriction fragment length
      polymorphisms with 7/18 restriction endonucleases used to digest whole genomic
      mouse DNA from the parental strains. BglII and DraI RFLPs for Creb-1 were scored
      on a subpanel of 16/207 known recombinants between Cryg and Lsh/Vil, yielding
      2/16 recombinants between Cryg and Creb-1 and 14/16 recombinants between Creb-1
      and Lsh/Vil. The 16/207 recombinants observed between Lsh/Vil and Cryg provide an
      estimated recombination frequency of 0.077 +/- 0.019, equivalent to a map
      distance of 7.7 +/- 1.9 cM. This is in good agreement with previously published
      map distances. The number of recombinants observed between Creb-1 and the other
      markers place Creb-1 approximately 1 cM distal to Cryg and 7 cM proximal to
      Lsh/Vil.

PMID- 1358812
TI  - Chromosome 11p15 deletions in human malignant astrocytomas and primitive
      neuroectodermal tumors.
AB  - Chromosome 11p15 deletions occur frequently in several types of human cancer,
      both sporadic and familial, suggesting that a tumor suppressor gene is present
      within the deleted chromosome region. We carried out a restriction fragment
      length polymorphism analysis of chromosome 11p in two types of human brain
      tumors: malignant astrocytoma, the most common glial tumor in adults; and
      primitive neuroectodermal tumor (PNET), a malignant embryonic tumor that afflicts
      children. Loss of heterozygosity was found in 11/43 malignant astrocytomas (26%)
      and in 3/11 PNETs (27%). Deletion mapping revealed a region of loss on chromosome
      11p (p15.4-pter) that was common to both tumor types. To determine whether the c
      H-ras gene, located on chromosome 11p in the common region of deletion, was a
      candidate gene, we analyzed polymerase chain reaction products corresponding to
      all four c-H-ras coding exons for single-strand conformation polymorphisms. The
      absence of electrophoretic mobility shifts in tumor DNA compared to leukocyte DNA
      indicated that c-H-ras gene mutations were most likely not present. These results
      suggested that loss of a gene on chromosome 11p15 distinct from c-H-ras is an
      important step in tumorigenesis within the central nervous system in both
      children and adults.

PMID- 1358813
TI  - The gene for lysyl oxidase maps to mouse chromosome 18.

PMID- 1358814
TI  - CD3+ T cells in severe combined immunodeficiency (scid) mice. VI. Rescue of scid
      derived, IgM-producing B cells by transfer of CD4+ CD8- T cells from various
      lymphoid organs.
AB  - Intravenous injection of purified CD4+ CD8- T cells from thymus, spleen or lymph
      nodes of adult dm2 donor mice (H-2d, Ld-, IgMa) into young C.B-17 scid/scid
      (scid) mice (H-2d, Ld+, IgMb) partially and selectively reconstituted the splenic
      CD4+ T-cell compartment of recipient scid mice. This was demonstrated by
      cytofluorographic analyses, histological examinations, growing donor-derived CD4+
      T-cell lines in vitro from spleens of transplanted scid mice, and serial passage
      of Ld-, CD3+CD4+CD8- T-cell lines through young scid recipients for more than 1
      year. Host-derived IgMb appeared in sera of all CD4+ T-cell-transplanted young
      scid mice, while none of the sex- and age-matched, non-transplanted control scid
      mice was Ig+. B-cell leakiness was most efficiently induced by transfer of low
      numbers of adult CD4+ CD8- thymocytes: transfer of 10(3) purified CD4+ CD8-
      thymocytes efficiently rescued scid-derived B cells, while transfer of 2 x 10(7)
      non-fractionated thymocytes from the same donor mouse was inefficient. Serum
      antibodies of scid mice with T-cell-induced B-cell leakiness stained congenic
      'double-positive' (CD4+ CD8+) thymocytes and immunoprecipitated protein bands
      with an apparent MW of 14,000, 28,000, 43,000, 65,000 and 80,000 from 125I
      labelled thymocytes. These data indicate that repopulation of peripheral lymphoid
      organs with CD4+ T cells is always accompanied by partial co-reconstitution of
      the B-cell system, and raises the question of the interdependence of these two
      lymphocyte subsets.

PMID- 1358816
TI  - T cell receptor alpha-chain polymorphic allele frequencies in Caucasians and
      Polynesians.
AB  - Restriction length polymorphisms in the variable and constant regions of the T
      cell receptor alpha-chain were examined in 42 Caucasians, 29 Maoris and 27
      Pacific Islanders. Southern blots of Taq I digested DNA were hybridized with the
      T cell receptor alpha-chain probe pY14. Our results confirm that a 1.4 kb T cell
      receptor alpha chain-Taq 1 band is allelic to a 0.5 kb band. A significant
      difference in the frequency of the 1.4 and 0.5 kb alleles of the variable region
      of the alpha-chain was detected in Caucasians when compared with Maoris or
      Pacific Islanders (P < 0.0001). No differences in the frequency of the 2.0 and
      7.0 kb alleles of the constant region gene were detected between any of the
      racial groups. These data may be relevant to ethnic differences in susceptibility
      to immune disorders.

PMID- 1358815
TI  - Subsets of null and gamma delta T-cell receptor+ T lymphocytes in the blood of
      young pigs identified by specific monoclonal antibodies.
AB  - Rat monoclonal antibodies (mAb) against isolated pig Null T cells were derived
      using a novel two-colour cytofluorometric assay. One (MAC320) identified all
      blood CD2-sIg- 'Null' cells (present at up to approximately 6 x 10(6)/ml).
      Another type (MAC319 and MAC318) identified a subset comprising approximately 60%
      or approximately 30% of the Null cell population. This percentage appears
      genetically determined. This subset partially overlapped with a gamma delta T
      cell receptor+ (TcR+) population which consisted of approximately 40% of Null T
      cells. The antibodies did not react with other leucocyte or lymphocyte
      populations. In non-reducing conditions, MAC320 precipitated two molecules at
      approximately 270,000-280,000 MW in SDS-PAGE; the larger of which was also
      precipitated by MAC319 (and MAC318, which binds to the same epitope). Under
      reducing conditions, MAC320 immunoprecipitated two or three polypeptide chains at
      approximately 130,000-160,000 MW; MAC319 precipitated only the largest of these
      polypeptides. The large MAC319+ MAC320+ molecule on one subset is removed by
      bromelain treatment; the smaller MAC319- MAC320+ molecule on the remaining Null
      cells is not bromelain sensitive. Several properties of this new antigen complex
      specific to pig Null T cells show that it is distinct from the ruminant T19
      complex.

PMID- 1358817
TI  - Immunosuppressive factor from liver and its influence on T cell development.
AB  - An endogenous immunosuppressive factor from liver, named ISF-70, of 70 kDa was
      studied with respect to mouse thymocyte maturation and expression of
      differentiation antigens in vitro. This factor induced dose-dependent alternative
      changes in thymocyte viability curves for 72 h incubation. Augmentation of viable
      cells was accompanied by a decrease in DNA synthesis and an increase in Lyt-2
      positive cells. A correlation was observed between thymocyte proliferation, Lyt-2
      expression and the action of ISF-70. It was found that ISF-70 distribution on
      thymocytes coincided with that of Lyt-2 antigen. The role of this factor in
      thymocyte developmental pathways and self-tolerance is discussed.

PMID- 1358818
TI  - Construction of a quadroma to alpha-endorphin/horseradish peroxidase using an
      actinomycin D-resistant mouse myeloma cell line.
AB  - A hybrid hybridoma (quadroma), secreting antibodies with double specificity to
      alpha-endorphin (alpha-EP) and horseradish peroxidase (HRP), has been produced.
      The bispecific antibodies constituted about 28-29% of all immunologically active
      IgG, produced by quadroma. The quadroma was isolated by fusion of two mouse
      hybridomas (anti-HRP and anti-alpha-EP) with distinct phenotypes: double mutant
      AMDR/HAT(S), and wild type (AMDS/HATR). A novel strategy for the construction of
      a double-mutant was applied, based on the use of an actinomycin D-resistant
      (AMDR) mouse myeloma for initiation of one of the parental hybridomas.

PMID- 1358819
TI  - Thy-1 antigen-mediated adhesion of mouse lymphoid cells to stromal cells of
      haemopoietic origin.
AB  - Thy-1 antigen is one of the widespread cell surface antigens. The antigen is
      expressed in the cells of a wide variety of different tissues and species and its
      pattern varies considerably during development and among species. Although the
      Thy-1 is one of the members of Ig-superfamily its function(s) remain unknown.
      Here we show that monoclonal antibodies to mouse Thy-1.2 antigen prevent adhesion
      of Thy-1.2-positive mouse T-leukemic cells 127 to monolayers of two mouse bone
      marrow stromal cell lines (14F1.1 and MBA-15). The same antibodies do not prevent
      adhesion of cell 127 to monolayers of two other mouse bone marrow stromal cell
      lines (MBA-2.1 and MBA-1.1.1) and to a wide spectrum of different normal and
      tumor mouse cell lines. A characteristic of the cell line 14F1.1 is the ability
      to support growth of mouse haemopoietic stem-cells. This data suggest that cells
      of stromal lines 14F1.1 and MBA-15 contain on their surface a specific ligand for
      the Thy-1 molecule. Cell-cell interaction via this ligand and the molecule on the
      cell surface may be an important step for development of certain lineages of
      cells.

PMID- 1358821
TI  - Antihistaminic efficacy of Ranitidine with & without Dimethendine maleate on
      histamine-induced cutaneous reactions.
AB  - The effect of Ranitidine, the H2-receptor antagonist, was investigated on
      cutaneous response to intradermal injection of histamine in healthy volunteers in
      a controlled, randomized, cross over study. The response was compared with that
      of the H1-receptor blocker; Dimethendine maleate used alone and in combination
      with the two antagonists. Reduction in the wheal area was significant in subjects
      pretreated with Ranitidine alone (P less than 0.05), and Dimethendine maleate
      alone (P less than 0.05); the combination of the two antagonists, did not produce
      additional reduction. Reduction in erythema area was not significant with
      Dimethendine maleate alone, but significant with Ranitidine alone (P less than
      0.01). With the combination of the two antagonists the reduction was not more
      significant than with Ranitidine alone. The flare response scoring on visual
      analogue scale was not reduced significantly by Dimethendine maleate alone but
      reduced significantly by Ranitidine alone (P less than 0.10), and by combination
      of Ranitidine and Dimethendine maleate (P less than 0.05). Thus, Ranitidine
      appears to be more effective than Dimethendine maleate in reducing the erythema
      area and intensity of flare response and equieffective in reducing wheal response
      to histamine injection.

PMID- 1358820
TI  - Apparently non-expressed alleles of factor B (BF) code for hypomorphic proteins.
AB  - In three families with an apparent non-expressed factor B (BF) allele (BF*Q0),
      advanced methods of isoelectric focusing for the determination of BF F subtypes
      revealed different hypomorphic BF products (BF QL) with functional hemolytic
      activity expressed by the assumed BF*Q0 allele. A Taq I and a Msp I restriction
      fragment length polymorphism as well as the Ba fragment of the expression
      products showed banding patterns for the BF*QL alleles corresponding to BF S
      types, whereas an altered Bb fragment was seen in two BF QL products. In one
      family an intragenic recombination site within the Bb part of the BF gene was
      assumed. Investigations of factor B and its conversion fragments, as demonstrated
      by the used methods, allow to complement molecular genetic investigations of
      BF*Q0 alleles in heterozygous genotypes on a protein level. We conclude that
      apparently non-expressed alleles of factor B code for hypomorphic but
      functionally active proteins.

PMID- 1358822
TI  - Whole body autoregulation in reduced renal mass hypertension.
AB  - Whole body autoregulation in conscious rats can be shown in the absence of the
      rapid acting neural and hormonal controllers of blood pressure. It is
      hypothesized that this phenomenon is responsible for the gradual rise of vascular
      resistance observed in volume-dependent forms of hypertension such as reduced
      renal mass-salt-induced hypertension. To examine the hypothesis, we evaluated the
      gain of whole body autoregulation at various stages of reduced renal mass
      hypertension to determine if acute autoregulatory capacity is altered during
      chronic hypertension. Rats underwent reduced renal mass surgery (nephrectomy plus
      70% reduction of remaining kidney) and were studied at 2 (n = 8), 4 (n = 6), and
      6 (n = 7) weeks after high salt diet. Control rats (n = 6) underwent nephrectomy
      and sham surgery and were studied after 2 weeks of high salt diet. All reduced
      renal mass rats showed progressive hypertension (2 weeks, 136 +/- 5; 4 weeks, 157
      +/- 8; and 6 weeks, 171 +/- 10 mm Hg) compared with sham rats (113 +/- 4 mm Hg).
      We observed an increase in basal level of total peripheral resistance index after
      neurohumoral blockade in reduced renal mass rats (2 weeks, 1.64 +/- 0.06; 4
      weeks, 1.79 +/- 0.10; and 6 weeks, 1.89 +/- 0.09 mm Hg.100 g-1.min-1.ml-1)
      compared with sham rats (1.56 +/- 0.10 mm Hg.100 g-1.min-1.ml-1).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1358823
TI  - Endothelial role in ouabain-induced contractions in guinea pig carotid arteries.
AB  - The influence of endothelium on the direct contractile effects of ouabain in
      vascular smooth muscle was analyzed in isolated perfused guinea pig carotid
      arteries. After blocking the neurogenic component of the glycoside contraction
      with alpha-adrenergic receptor blocking drugs or treating the animals with
      reserpine, ouabain-induced contractions were markedly reduced in vessels with
      intact endothelium. However, removal of the vascular endothelium from
      reserpinized carotid arteries resulted in ouabain-induced contractions similar to
      those observed in control arteries. These effects were not mimicked by the
      inhibitor of nitric oxide NG-monomethyl L-arginine or by the cyclooxygenase
      blocker indomethacin. Bioassay experiments suggested that these endothelial
      effects are mediated by diffusible factors. Uptake of 86Rb to measure sodium pump
      activity was significantly reduced by removal of the endothelium. These results
      suggest the existence of an inhibitory modulation by the endothelium of
      contractions induced by ouabain, likely mediated by a diffusible factor (or
      factors) released from these cells. The nature of this substance is unknown, but
      it is neither related to prostaglandins nor a nitric oxide-related compound. Its
      mechanism of action could be the stimulation of vascular sodium pump activity,
      the antagonism of the pump's inhibition by ouabain, or both.

PMID- 1358824
TI  - Pulmonary involvement in nephropathia epidemica as demonstrated by computed
      tomography.
AB  - In a prospective study 19 adult patients with nephropathia epidemica were
      examined in the acute phase of disease with computed tomography (CT) of the lungs
      and conventional chest radiography. Infiltrates and/or pleural effusions were
      seen in ten of 19 patients. In two of the patients, abnormalities were disclosed
      only by CT. Patients with pathologic radiography findings had a more pronounced
      inflammatory response, as measured by C-reactive protein and leukocyte count,
      than did those with normal radiography findings. It is concluded that
      radiological evidence of pulmonary involvement is a common finding early in the
      course of nephropathia epidemica. The possibility that the lung may be a site of
      viral replication merits further investigation.

PMID- 1358826
TI  - Immunohistochemical demonstration of androgen receptors on testicular blood
      vessels.
AB  - Using an antiserum directed against the human and rat androgen receptor we have
      used immunohistochemistry to demonstrate that nuclear androgen receptors are
      present in the muscular layer of almost all arteries within the rat testis. These
      receptors are apparently influenced by testosterone. They disappear after Leydig
      cell depletion induced by ethanedimethane sulphonate (EDS) and return after
      testosterone treatment. It is suggested that testicular blood vessels could be a
      target-organ for androgens and may mediate some of the effects of androgens on
      the testicular microcirculation.

PMID- 1358825
TI  - S-fimbriae mediated adhesion of Escherichia coli to human buccal epithelial cells
      is age independent.
AB  - S-fimbriated Escherichia coli, which cause sepsis and meningitis in the newborn,
      bind to sialic acid-containing glycoprotein structures on the surface of human
      buccal epithelial cells. The dependence of this binding on host age was examined.
      S-fimbriated E. coli adhered in comparable numbers to cells in newborns, infants,
      children and adults (23.0 +/- 8.6; 23.1 +/- 11.5; 24.7 +/- 7.9; 28.9 +/- 8.8).
      Thus, the increased susceptibility of neonates to infections caused by S
      fimbriated E. coli cannot be explained by enhanced adhesion to epithelial cells.

PMID- 1358827
TI  - Suppression of basal, PMA- and IFN-alpha-, but not IFN-gamma-induced expression
      of HLA class I in v-myc-transformed U-937 monoblasts.
AB  - Recent studies have suggested that certain oncogenes, in particular members of
      the myc family, may be involved in the down-regulation of HLA class-I antigen
      expression observed in many types of tumor. We report that constitutive
      expression of an OK10 v-myc gene in human monoblastic U-937 cells results in a
      reduced expression of HLA class-I cell-surface expression and decreased levels of
      HLA class-I protein and mRNA. All class-I alleles, with the possible exception of
      HLA A3, were affected, as shown by one-dimensional isoelectric focusing (ID-IEF).
      Basal expression of the beta 2m chain was also reduced, although to a lesser
      extent. In addition, we show that the PMA-, and at least partially the IFN-alpha
      induced increase in HLA class-I antigen expression, was inhibited in U-937-myc
      cells both at the protein and the mRNA level. In contrast, the response to IFN
      gamma was normal. Another important difference in the response to IFN-gamma and
      alpha was that, while IFN-gamma abrogated the v-myc block of PMA-induced
      differentiation of U-937 cells, as previously reported, IFN-alpha did not. Our
      data show that v-myc negatively affects the regulation of both basal and
      inducible HLA class-I antigen expression.

PMID- 1358828
TI  - Treatment of liver metastases of human colon cancers in nude mice with
      somatostatin analogue RC-160.
AB  - Hepatic metastases of colon 320 DM and WidR human colon cancers in nude mice were
      treated by s.c. injections of somatostatin analogue RC-160 for 4 weeks. Chronic
      administration of RC-160 significantly inhibited the incidence and growth of
      liver metastases of these 2 colon-cancer cell lines. After RC-160 treatment, the
      incidence of liver metastases decreased by 25% for colon 320 DM cells and by
      37.5% for WidR cells. The mean number of metastatic tumors in each liver
      decreased by 47.9% for colon 320 DM and 42.6% for WidR. Survival times of mice
      with liver tumors of colon 320 DM and WidR cells were prolonged by 20 days and 7
      days, respectively. The inhibitory effect of RC-160 on the growth of these 2
      colon cancers implanted s.c. was also observed. After administration of RC-160
      for 4 weeks, the mean tumor volume in the treated groups was only 39.8% of that
      of controls for the colon 320 DM line and 58% for the WidR line. Tumor-growth
      rate and final tumor weight were also significantly decreased, while tumor-volume
      doubling time and tumor-growth delay time were prolonged. The effect of RC-160 on
      cellular proliferation in the tumors was studied by in vivo labelling with
      bromodeoxyuridine and immunoperoxidase staining. The mean labelling index in the
      treatment group was reduced by 14.9% and 19.5%, respectively, for colon 320 DM
      and WidR tumors. The cytostatic effect of RC-160 was also evident from the
      apparent reduction in DNA and protein content in the tumor tissues of these
      cancer lines. Our findings suggest that somatostatin analogue RC-160 may be
      useful for the treatment of patients with hepatic metastases of colon cancer.

PMID- 1358829
TI  - Atrial fibrillation and flutter after coronary artery bypass surgery:
      epidemiology, risk factors and preventive trials.
AB  - Atrial fibrillation and atrial flutter are common arrhythmias after coronary
      artery bypass grafting. Although the consequences of the arrhythmia are generally
      not life-threatening, it constitutes a major clinical problem often requiring
      conversion to sinus rhythm. Atrial fibrillation or flutter can result in
      hypotension, heart failure, pneumonia, and stroke. This article reviews the
      literature on epidemiology, electrophysiology, risk factors, and preventive
      trials. The major conclusions are: (1) In patients undergoing coronary artery
      bypass surgery, the incidence of postoperative atrial fibrillation or flutter is
      20-30%, the peak incidence being on the second or third postoperative day. (2)
      The strongest independent preoperative predictor for atrial fibrillation or
      flutter is the patients' age. (3) Intra-atrial conduction delay recorded pre and
      peroperatively may predict development of atrial fibrillation. (4) Peroperative
      inducibility of atrial fibrillation by pacing the right atrium may identify
      patients at risk for postoperative atrial fibrillation. (5) Development of
      postoperative atrial fibrillation or flutter has not been associated with
      peroperative or postoperative events. (6) The specificity and sensitivity of age
      and other possible relevant factors for prediction of atrial fibrillation or
      flutter after coronary artery bypass grafting is low. (7) No effective
      prophylactic regimen has yet been established.

PMID- 1358830
TI  - Amlodipine in patients with stable angina pectoris treated with nitrates and beta
      blockers. The influence on exercise tolerance, systolic and diastolic functions
      of the left ventricle.
AB  - The effects of 5 and 10 mg of amlodipine and of placebo were compared in 21
      patients with stable angina pectoris and multivessel coronary artery disease. The
      blind comparison was performed by means of bicycle ergometry and stress
      echocardiography using esophageal stimulation of the left heart atrium. All
      patients subsequently received placebo, amlodipine 5 mg and 10 mg for 2 weeks. In
      bicycle ergometry both doses of amlodipine in comparison with placebo
      significantly lowered the ST segment depression in lead V5 and prolonged the time
      to onset of angina. The exercise duration was significantly prolonged only after
      10 mg of amlodipine. In stress echocardiography 10 mg of amlodipine significantly
      improved ejection fraction and reduced wall motion score during stimulation and
      increased peak velocity of relaxation of left ventricular posterior wall at rest
      and immediately after stimulation. In the patients with left ventricular end
      diastolic pressure < or = 20 mmHg, amlodipine reduced the ratio of peak
      transmitral flow velocity in atrial contraction to that in early diastole (A/E)
      at rest and shortened deceleration time at rest and immediately after
      stimulation. Amlodipine in patients with stable angina pectoris significantly
      improved the exercise tolerance and the function of the left ventricle in a dose
      dependent way. Amlodipine was well tolerated.

PMID- 1358831
TI  - Combined two-dimensional and Doppler echographic examination of internal mammary
      artery grafts from the supraclavicular fossa.
AB  - The noninvasive examination of internal mammary artery grafts is gaining
      importance with the increasing use of this vessel in the surgical treatment of
      coronary atherosclerosis of the left anterior descending artery. We studied 36
      patients (37 internal mammary artery grafts) with combined two-dimensional and
      pulsed Doppler echography from the supraclavicular fossa. Adequate visualization
      and Doppler signals were obtained in 95% of arterial grafts. Twenty-four grafts
      leading to an area without evidence of old myocardial infarction or ischemia and
      10 grafts leading to an area of old myocardial infarction but without evidence of
      ischemia on exercise showed a significant decrease of the peak systolic velocity
      and of the peak systolic velocity/peak diastolic velocity ratio as compared to
      the controls, which consisted of the contralateral internal mammary arteries in
      situ. One patient with a distally subtotally occluded mammary artery graft had a
      flow pattern different from the other bypassed mammary arteries. It seems that
      combined two-dimensional and pulsed Doppler echography is a useful method to
      evaluate the functional status of internal mammary artery grafts.

PMID- 1358832
TI  - Open trial of tacrine therapy in 70 HIV-infected patients.
AB  - The purpose of this study consisted in following-up the biological and clinical
      parameters in HIV infected patients treated with tacrine (THA). THA (150-300
      mg/d) was administrated to 70 patients (39 IVC I and 31 IVC II and III). Thirty
      five were treated after discontinuation of AZT treatment and 35 as a first
      intention treatment. Thirty (43%) patients showed an increase in the CD4+ cell
      count by more than 50% relative to pretreatment levels and fifteen (21%) showed
      an increase of more than 25%. p24 antigenemia (Ag p24) became negative in eight
      of the twenty-seven patients who were initially positive, and decreased by 25 and
      50% in nine and six patients, respectively. Ag p24 was therefore decreased in 80%
      of the patients. From a clinical point of view, there were two deaths (3%) and
      five opportunistic infections (7%). The treatment with THA was stopped in five
      patients because of side effects (nausea, rash). Neither hepatotoxicity,
      hematotoxicity, nor pancreatitis was observed during the THA treatment. In group
      II and III only two patients (6%) developed an opportunistic infection.

PMID- 1358833
TI  - Pharmacokinetic/pharmacodynamic characteristics of the beta-2-agonists
      terbutaline, salbutamol and fenoterol.
AB  - The clinical pharmacokinetics and pharmacokinetic/dynamic properties of the beta
      adrenergic drugs fenoterol, salbutamol and terbutaline are reviewed. Sulfate
      conjugates are the main metabolites in man. The protein binding of these
      derivatives is rather weak with most pronounced binding observed e.g. fenoterol
      (40%). Disposition after parenteral administration shows a multi-exponential
      behavior for all the substances with linear but also stereo-selective
      pharmacokinetics. After parenteral administration, the drugs are mainly
      eliminated by renal processes while after oral administration a pronounced
      metabolic clearance (high first pass effect) is responsible for a low
      bioavailability, especially for fenoterol (2%). The total clearance for fenoterol
      is about twice that of salbutamol and terbutaline. Seven to 15% of the delivered
      aerosol reach typically the systemic circulation. In patients with respiratory
      disorders, pulmonary absorption is however highly dependent on the disease state.
      Pharmacokinetics in children do not significantly differ from adults when
      expressed per kg body weight. Patients with renal failure but not asthmatics show
      changed pharmacokinetic profiles. Only insignificant interactions with other
      drugs have been found. Pharmacokinetic/dynamic modeling approaches indicated that
      fenoterol is 25 times more active at the site of action than salbutamol and
      terbutaline, but all three drugs show similar bronchopulmonary selectivities.
      When the overall clinical activity, determined by pharmacokinetic and dynamic
      properties is compared, the activity gap is reduced: fenoterol (8) greater than
      salbutamol (2) greater than terbutaline (1). Differences in the first pass effect
      even inverse the pattern after oral administration. PK/PD modeling quantified the
      pulmonary effect after inhalation and suggested that the higher incidence of side
      effects for fenoterol might be linked to an overdosing problem. The application
      of PK/PD principles may improve the clinical usage and therapy of beta-2
      adrenergic drugs.

PMID- 1358834
TI  - Bispecific antibodies and targeted cellular cytotoxicity. Ostuni, Italy, June 13
      17, 1992.

PMID- 1358835
TI  - Familial granuloma annulare.

PMID- 1358836
TI  - Laparoscopy bashing.
AB  - Therapeutic laparoscopy--operative laparoscopy--has been employed in increasing
      proportion to laparotomy for various gynecological pathologies. Although
      routinely used for sterilization procedures, acceptance first for tubal pregnancy
      and then for other adnexal surgery has been gained. Now advocates are using the
      laparoscope for assisted hysterectomy, lymph node dissections, and other
      questionable indications. Coupled with the emergence of rapidly changing
      technology is the problem of adequate teaching of postgraduate physicians and
      proper credentialing of individuals, especially in smaller community hospitals.

PMID- 1358837
TI  - Ovarian consequences of the transient interruption of combined oral
      contraceptives.
AB  - The combined oral contraceptive pill is an efficient means of contraception. It
      acts at different levels of the genital tract. Despite its efficiency, it is
      universally suggested that patients take the pill at regular daily intervals.
      Little attention has been given to the question of what happens if you miss the
      pill one day or more. A study was undertaken to evaluate the consequences of pill
      misses at different times of the cycle. Forty-seven young, healthy, normally
      menstruating patients voluntarily enrolled. All were given Cilest (ethinyl
      estradiol 35 micrograms and norgestimate 250 mg, Cilag France) for 21 days
      without any misses. Then, after a 7-day interval, they were prescribed one (group
      1), two (group 2), three (group 3) or four days of pill misses, to occur
      respectively on day 1 (group a), 6 (group b), 12 (group c) or 18 (group d) of a
      new 21 day cycle; supplementary contraceptive means were recommended. Four
      patients had no miss prescribed and served as controls. Ovarian function was
      evaluated with daily estrogen measurements (E1 + E2 enzymatic dosage, BioMerieux,
      France) and ultrasound examinations. When required, because of significant
      increase in estrogen or because of follicular growth detected on ultrasound, LH
      and progesterone were measured. None of the patients experienced a normal
      ovulation. Four patients (1 control, 1 from group 2a, and 2 from group 3a) had a
      significant increase in estrogen levels and had a follicular image on
      ultrasounds. One of them (group 3a) had a follicular rupture, but none had a LH
      surge or increase in progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358838
TI  - Combined therapy with bromocriptine and clomiphene citrate for patients with
      normoprolactinemic amenorrhea.
AB  - The purpose of this study was to investigate the combined effect of bromocriptine
      (Brc) and clomiphene citrate (Cl) treatment on 40 patients with
      normoprolactinemic amenorrhea who failed to respond to Cl alone. The ovulation
      rate in this treatment was 57.3% (23/40) in the 40 cases, 55.6% (99/178) in 178
      cycles; the pregnancy rate was 26.7%. This treatment was effective in 14 of 21
      women with polycystic ovary-like syndrome (66.7%). Among those women who
      responded to treatment, prolactin (PRL) and LH levels were significantly
      decreased. Estradiol and progesterone levels were significantly increased in the
      patients who responded. Before treatment, the responsiveness of LH to LHRH among
      responders to Brc/Cl therapy was significantly higher than among the
      nonresponders. After treatment, the LH-releasing response following a conjugated
      estrogen injection in the patients who responded to the treatment was
      significantly greater than that in the patients who did not respond. The results
      suggest that the therapeutic effect of this treatment may be primarily due to the
      restoration and improvement of the impaired hypothalamo-pituitary axis.

PMID- 1358839
TI  - Mullerian remnants in complete androgen insensitivity syndrome.
AB  - Patients with complete androgen insensitivity syndrome rarely have Mullerian
      remnants. A patient with this syndrome found to have a microscopic fallopian tube
      at the time of gonadectomy is described and possible etiologies for the finding
      are discussed.

PMID- 1358840
TI  - Clinical review of a monophasic oral contraceptive containing desogestrel and
      ethinyl estradiol.

PMID- 1358841
TI  - Prevalence of polycystic ovaries by transvaginal ultrasound and serum androgens.
AB  - The present study compares the ovarian area and the androgen levels
      (testosterone, free testosterone, SHBG, testosterone/SHBG ratio) in the two
      patterns (peripheral cystic pattern, general cystic pattern) of polycystic
      ovaries diagnosed by transvaginal ultrasound. The results were as follows. (1)
      The ovarian area of the peripheral cystic pattern group of polycystic ovaries was
      significantly greater than that of normal controls, but in the general cystic
      group it was not. (2) Serum levels of testosterone and free testosterone, and the
      testosterone/SHBG ratio in patients with polycystic ovary syndrome were
      significantly higher than those of healthy controls; but with ultrasonographic
      classification, there was no significant difference between the peripheral cystic
      and general cystic groups. (3) In the polycystic ovary syndrome, elevated levels
      of testosterone and free testosterone, and of the testosterone/SHBG ratio were
      observed in approximately half of the patients. Ovarian morphology was different,
      but androgen status was similar in the two patterns of polycystic ovaries.

PMID- 1358842
TI  - Endoscopic carbon dioxide laser ovarian wedge resection in resistant polycystic
      ovarian disease.
AB  - Clomiphene citrate therapy has been found to improve the infertility rate in
      women suffering from polycystic ovarian disease (PCOD). However, there still
      exists a group of women with PCOD who fail to respond to clomiphene citrate or
      human menopausal gonadotropin/human chorionic gonadotropin or
      urofollitropin/chorionic gonadotropin treatment, an ovarian wedge resection by
      laparotomy approach which has been known for 50 years. Within the last decade,
      translaparoscopic electrocautery and laser drilling techniques have been
      utilized. In 1986, a translaparoscopic carbon dioxide laser ovarian wedge
      resection was introduced for resistant PCOD. This paper describes the surgical
      principle of a translaparoscopic carbon dioxide laser ovarian wedge resection.
      This type of treatment results in a 75% crude conception rate, with a 67% rate of
      healthy live birth. There was an 8% postsurgical adhesion rate among 12 cases
      that were incorporated into the study. This mode of therapy may prove to be very
      useful, safe, easy to perform, and cost effective as a second-line therapy for
      resistant PCOD in cases where medical inductions fail to achieve ovulation.

PMID- 1358843
TI  - Etiological factors of male infertility in Africa.
AB  - Of the 595 infertile African males studied, 192 (30.8%) were azoospermic and 413
      (69.40%) had oligospermia. Azoospermia was caused by obstruction to the vas
      and/or epididymis in 44% of cases and testicular lesions in the remaining 56% of
      cases, whilst the oligospermia was probably caused by obstruction in 4.7% of
      cases and testicular lesions in 85.3%. Bilateral testicular biopsies were
      performed on 302 patients. A variety of pathological conditions were observed;
      the most prevalent was hypospermatogenesis, in 12% of cases. A significant
      portion (37.2%) of patients without testicular biopsies had clinically detectable
      testicular or epididymal abnormalities. There was a higher incidence (12%) of
      inflammatory testicular or prostatic conditions in this study as compared with
      those found in Europeans, suggesting that inflammatory conditions contribute more
      to male infertility in Africa. Only a single case of chromosomal abnormality was
      detected.

PMID- 1358844
TI  - Plasminogen activator: the identification of an additional proteinase at the
      outer acrosomal membrane of human and boar spermatozoa.
AB  - We have recently shown that spermatozoa of various species contain both types of
      plasminogen activator, the tissue-type (t-PA) and the urokinase-type (u-PA). In
      the present study, the localization of t-PA and u-PA in plasma membrane and outer
      acrosomal membrane of human and boar spermatozoa has been investigated. The
      identification of the type of the plasminogen activator (t-PA or u-PA) was made
      immunologically. In human spermatozoa, the outer acrosomal membrane and plasma
      membrane contained both types of plasminogen activator (t-PA and u-PA); in
      addition, t-PA antigen was measured. In boar spermatozoa, the outer acrosomal
      membrane contained only t-PA, whereas plasma membrane contained both types of
      plasminogen activator (t-PA and u-PA). Plasminogen activator inhibition (PAI) has
      also been demonstrated in plasma and outer acrosomal membranes of both species
      and identified as PAI-1 in membranes of human spermatozoa.

PMID- 1358845
TI  - Flow cytometric comparison between swim-up and Percoll gradient techniques for
      the separation of frozen-thawed human spermatozoa.
AB  - Viable human spermatozoa were recovered from cryopreservation by either swim-up
      or Percoll density gradient techniques and their cell-surface oligosaccharide
      components were compared to those of fresh sperm. Sperm were labeled with FITC
      Con A and analyzed by fluorescence microscopy and flow cytometry. By fluorescence
      microscopy, fresh sperm were uniformly labeled in the neck region alone. Frozen
      thawed sperm, obtained by either swim-up or Percoll density gradients, showed two
      patterns of staining: one sperm population was stained in the neck region only,
      whilst another showed staining in both the neck and acrosome regions. No
      difference between sperm recovered by the two techniques was apparent. Flow
      cytometry profiles of fresh sperm revealed a single peak of fluorescence, whereas
      cryopreserved sperm gave two peaks of fluorescence. Samples recovered by Percoll
      density gradient contained significantly more sperm with the same fluorescence
      pattern as that observed for fresh sperm than did those recovered by swim-up.
      Cryopreservation alters the cell-surface oligosaccharide components of
      spermatozoa. Recovery of cryopreserved sperm by Percoll density gradient yields a
      greater proportion of sperm which resemble fresh sperm than does swim-up.

PMID- 1358846
TI  - Precursors of molecules related to mammalian opioid peptides in brain of a marine
      worm.
AB  - Total mRNA were extracted from brain of Nereis diversicolor (Annelida,
      Polychaeta) and were translated in vitro or in ovo. The newly synthesized
      polypeptides were analyzed through electrophoresis of immunoprecipitated products
      or the Western blotting technique using polyclonal antibodies raised against
      mammalian dynorphin 1-17 and mammalian alpha-neo-endorphin. Among the products
      translated in vitro, only one class of polypeptide of 70 kDa was recognized by
      anti-dynorphin 1-17 antibodies. Furthermore, some in ovo translated products as
      well as proteins extracted from brain of worms showed identical immunoreactivity.
      These polypeptides, 60-70 kDa, reacted with anti-dynorphin 1-17 and anti alpha
      neo-endorphin antibodies. These results suggest the existence of epitopes common
      to in ovo and in vitro translated products, to polypeptides extracted from the
      brain and to some mammalian opioid peptides of the prodynorphin family. We
      postulate the presence, in the brain of N. diversicolor, of precursors of
      peptides related to mammalian dynorphin 1-17 and alpha-neo-endorphin. Data
      reported in this investigation do not allow us to propose or even postulate the
      presence, in the brain of the worm, of one precursor molecule common to
      polypeptides related to mammalian dynorphin 1-17 and alpha-neo-endorphin.
      Furthermore, the Nereis precursor molecules exhibit a clear-cut difference in
      molecular mass with the mammalian prodynorphin: 70 kDa versus 30 kDa.

PMID- 1358848
TI  - Interaction of glucagon with artificial lipid bilayer membranes.
AB  - The enhancement of fluorescence emission from the tryptophan residue of glucagon,
      the quenching of that emission with acrylamide and with 5-doxyl and 16-doxyl
      stearic acid, circular dichroism spectra, the release of 6-carboxyfluorescein,
      and polarized infrared attenuated total reflection (IR-ATR) spectra were used to
      study the interaction of glucagon with intact lipid vesicles and flat bilayers.
      Dimyristoylphosphatidylcholine bound the peptide only below the main transition
      temperature, thus confirming earlier results of Epand et al. (1977). However, the
      peptide is also bound by vesicles of unsaturated lipids above their transition
      temperature, suggesting an influence of lipid area on the binding process.
      Circular dichroism showed that binding to such vesicles also increases the helix
      content of glucagon. The IR-ATR study and a comparison with dynorphin-A-(1-13)
      tridecapeptide revealed profound differences in orientation of the two peptides.
      The dichroic ratios and the derived order parameters indicated an isotropic
      orientation of the helical segments of glucagon, but did not exclude a principal
      orientation of the molecules lying flat on the membrane surface. In contrast, the
      axis of the dynorphin helix is clearly oriented normal to the interface. The two
      peptides also differ in their rates of 6-carboxyfluorescein release, suggesting a
      deeper penetration of the primary amphiphilic helix of dynorphin A-(1-13) than of
      the secondary amphiphilic helix of glucagon.

PMID- 1358849
TI  - N-alkoxycarbonyl-glutamic and aspartic acids. Studies on the activation and
      cyclodehydration and side-reaction encountered in analysis of glutamic acid using
      Fmoc-chloride.
AB  - N-Alkoxycarbonylaminodicarboxylic acids were reacted in dichloromethane with N
      ethyl-N'-(dimethylaminopropyl)carbodiimide hydrochloride, and with methyl
      chloroformate in the presence of N-methylmorpholine. Removal of secondary
      products by washing the mixtures with aqueous solutions gave good yields of the
      pure crystalline internal anhydrides. Anhydrides of N-benzyloxycarbonyl- (Z) and
      N-9-fluorenylmethoxycarbonyl-(Fmoc) L-glutamic and L-aspartic acids and of N
      tert.-butoxycarbonyl-L-aspartic acid were prepared in this way. The compounds
      were shown to be amenable to normal phase high-performance liquid chromatography
      (NP-HPLC) on a CN-column using tert.-butanol-hexane as solvent. The products of
      the reactions of Z- and Fmoc-glutamic acid with hot acetic anhydride were
      examined by nuclear magnetic resonance and NP-HPLC before and after methanolysis
      in an attempt to establish if any of the corresponding pyroglutamates were
      formed. The reaction of Fmoc-chloride with Fmoc-glutamate was examined for the
      same reason. It is concluded that the side product generated during the reaction
      of Fmoc-chloride with glutamic acid which is used for analysis of the latter is
      the N-protected internal anhydride and not the pyroglutamate as reported in the
      literature.

PMID- 1358847
TI  - Reduced peptide bond cyclic somatostatin based opioid octapeptides. Synthesis,
      conformational properties and pharmacological characterization.
AB  - The conformational and pharmacological properties that result from peptide bond
      reduction as well as the use of secondary amino acids in a series of cyclic
      peptides related to the mu opioid receptor selective antagonist D-Phe1-Cys2-Tyr3
      D-Trp4-Orn5-Thr6-Pen7+ ++-Thr8-NH2 (IV), have been investigated. Peptide
      analogues that contain [CH2NH] and [CH2N] pseudo-peptide bonds (in primary and
      secondary amino acids, respectively) were synthesized on a solid support.
      Substitution of Tyr3 in IV by the cyclic, secondary amino acid 1,2,3,4
      tetrahydroisoquinoline carboxylate (Tic) and of D-Trp4 with D-1,2,3,4-tetrahydro
      beta-carboline(D-Tca4), gave peptides 4 and 1, respectively. Both analogues
      displayed reduced affinities for mu opioid receptors. Conformational analysis
      based on extensive NMR investigations demonstrated that the backbone
      conformations of 1 and 4 are similar to those of the potent and selective
      analogue D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (I), while the conformational
      properties of the side chains of Tic3 (4) and D-Tca4 (1) resulted in
      topographical properties that were not well recognized by the mu opioid receptor.
      Peptide bond modifications were made including (Tyr3-psi[CH2NH]-D-Trp4), 3; (Tyr3
      psi[CH2N]-D-Tca4), 2; and (Cys2-psi[CH2N]-Tic3), 6. These analogues showed
      decreases in their mu opioid receptor affinities relative to the parent compounds
      IV, 1, and 4, respectively. 1H NMR based conformational analysis in conjunction
      with receptor binding data led to the conclusion that the reduced peptide bonds
      in 2, 3, 5, and 6 do not contribute to the process of discrimination between mu
      and delta opioid receptors, and in spite of their different dynamic behaviors
      (relative to 1 and 4), they are still capable of attaining similar receptor bound
      conformations, possibly due to their increased flexibility.

PMID- 1358851
TI  - Special issue on Glaucoma. 4th Congress of the European Glaucoma Society.
      Amsterdam, The Netherlands, 20-24 May 1992.

PMID- 1358850
TI  - Conformational studies of N-Tyr-MIF-1 in aqueous solution by 1H nuclear magnetic
      resonance spectroscopy.
AB  - N-Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) is an endogenous brain peptide with multiple
      effects on animal behavior. However, there have been no studies on the
      conformation of this tetrapeptide. In this report, we studied the conformation of
      N-Tyr-MIF-1 in aqueous solution by conventional one-dimensional and two
      dimensional (COSY and NOESY) 1H nuclear magnetic resonance spectroscopy at 300
      MHz. A complete set of assignments for the resolved resonances and approximate
      assignments for the overlapping resonances were made. The results demonstrate
      that N-Tyr-MIF-1 is in slow exchange between two conformers, most likely
      determined by the cis and trans states of the proline residue. The minor
      conformation represents 30 +/- 3% of the population over the temperature range
      from 3 degrees to 73 degrees. In the major conformation, the tyrosine aromatic
      ring appears to be close enough to interact directly with the proline pyrrolidine
      ring, as indicated by a strong temperature dependence of the proline C beta H, C
      delta H and C delta H' chemical shifts. In contrast, this interaction of the
      tyrosine and proline rings is not present in the minor conformation.

PMID- 1358852
TI  - Apraclonidine and clonidine: a comparison of efficacy and side effects in normal
      and ocular hypertensive volunteers.
AB  - We performed a prospective, randomized double blind study comparing the
      cardiovascular and intraocular pressure (IOP) effects of unilateral therapy with
      clonidine 0.125% and apraclonidine hydrochloride 1.0% in 15 normal and 15 ocular
      hypertensive volunteers. Baseline values were obtained prior to instillation. One
      drop of test medication (clonidine, apraclonidine or placebo) was instilled
      unilaterally, and the post-instillation measurements were taken at 1, 2, 4, 6 and
      8 hours. Apraclonidine 1% produced a maximum 31.4% +/- 6.9% (4.83 +/- 1.17 mmHg)
      decrease in mean IOP in ocular normotensive volunteers and 33.9% +/- 6.9% (10.10
      +/- 2.45 mmHg) in ocular hypertensive patients (p < 0.001). These values were
      22.1% +/- 6.9% (2.90 +/- 1.94 mmHg) and 22.7% +/- 6.9 (6.80 +/- 2.31 mmHg),
      respectively in clonidine group (p < 0.001). In apraclonidine group, there were
      no changes in contralateral IOP, blood pressure or pulse rate. Clonidine produced
      a significant decrease in contralateral IOP, but this reduction was not
      statistically significantly different than that of placebo. In clonidine group,
      there was no change in pulse rate, but a significant decrease in blood pressure.
      Eyelid retraction, conjunctival blanching and mydriasis were noted in eyes
      treated with apraclonidine. However there were no statistically and clinically
      significant changes in pupil size or interpalpebral fissure width with clonidine.
      This study suggests that apraclonidine appears to be safer and more effective
      ocular hypotensive agent than clonidine in treatment of glaucoma.

PMID- 1358853
TI  - Dopamine, dopaminergic drugs and ocular hypertension.
AB  - The study refers to the clinical experiences performed with several D1 and D2
      dopaminergic receptors agonists in 20 patients with high tension open angle
      glaucoma. The substances were administered topically as eye drops as well as an
      ocular eye bath. The parameter examined was intraocular pressure (IOP). The
      substances taken in consideration were: Dopamine, Ibopamine (dopamine analog),
      Fenoldopam and 3B90 (D1-receptor agonists) and Bromocriptine (dopaminergic
      agonist with higher affinity for D2 than for D1-receptors). It has been shown
      that all selective D1-receptors agonists induce a significant increase in IOP
      only in eyes with hydrodynamic disorders (p < 0.001). Such hypertensive effects
      could not be antagonized either by topically administered dopaminergic
      antagonists (Sulpiride, D2-receptors antagonist, and Haloperidol, non-selective
      dopaminergic antagonist) or by the pretreatment with the commonly used topical
      antiglaucomatous drugs. The only substance which proved able to inhibit the IOP
      increase induced by the D1-receptors agonists was the D1-selective antagonist SCH
      23390, suggesting that IOP increase may be a result of a stimulation of the D1
      receptors. The authors hypothesize that dopaminergic system may play a role in
      the regulation of aqueous humor hydrodynamics.

PMID- 1358856
TI  - [Borderline Kidney Function. Results with Piretanide and Ramipril. Symposium.
      Vienna, 14 December 1991].

PMID- 1358854
TI  - The scientific basis of antenatal care routines: the state of the art.
      Proceedings of a conference. Gimo, Sweden, May 21-23, 1990.

PMID- 1358855
TI  - [Drugs acting on the heart in therapy of silent myocardial ischemia].

PMID- 1358857
TI  - Human leukocyte antigen serologic and DNA typing of Behcet's disease and its
      primary association with B51.
AB  - Ninety Japanese patients with Behcet's disease (BD) were typed for human
      leukocyte antigen (HLA)-DRB1, -DQA1-, -DQB1, and -DPB1 alleles by the polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and for
      HLA-A, -B, -C, -DR, and -DQ antigens by conventional serologic typing. Serologic
      HLA typing showed a remarkably significant increase of HLA-B51 and a significant
      decrease of HLA-DQw1 in the patients with BD, especially those with ocular
      lesions including complete type, as compared with the control group (for B51, chi
      squared = 46.75, P corrected < 0.001, relative risk [RR] = 7.9; for DQw1, chi
      squared = 12.10, P corrected < 0.01, RR = 0.4). By PCR-RFLP genotyping, no
      significant difference was revealed in any class II alleles between the patient
      and the control groups in the corrected P value test, but P value analysis showed
      the significantly high frequency of DRB1*0802 and the significantly low
      frequencies of DQA1*0103, DQB1*0601, and DQB1*0501. No significant difference was
      observed in any DPB1 alleles by either P value analysis. These results indicated
      that the primary and primordial gene(s) responsible for the susceptibility to BD,
      especially related to ocular lesions, were not located in the HLA class II gene
      region but were in or very close to the HLA-B locus in the class I region. They
      also suggested the possibility that BD was a symptom complex associated with some
      independent diseases.

PMID- 1358858
TI  - MK-801 protects retinal neurons from hypoxia and the toxicity of glutamate and
      aspartate.
AB  - The protective effect of the anticonvulsant MK-801 and the antitussive
      dextromethorphan, which are both N-methyl-D-aspartate receptor antagonists, and
      kynurenic acid, a broad-spectrum excitotoxin antagonist, was tested in cultured
      rat retinal cells in an hypoxic environment. The protective effect of these
      antagonists also was tested in cultured retinal cells and in intact adult rat
      retinas exposed to the exogenous excitotoxins L-glutamic acid and N-methyl-D
      aspartic acid. MK-801 and kynurenic acid protected retinal neurons from hypoxic
      damage and from the toxicity of exogenous L-glutamic acid and N-methyl-D-aspartic
      acid. Dextromethorphan, a less potent antagonist, did not protect the retinal
      neurons from hypoxic damage or the toxicity of exogenous L-glutamic acid, but did
      attenuate N-methyl-D-aspartate toxicity. These results provide evidence that the
      synaptic release of excitatory transmitters, most likely glutamate and aspartate,
      mediate the death of hypoxic retinal neurons. Compounds related to MK-801 may
      have possible therapeutic applications in the management of retinal ischemia.

PMID- 1358859
TI  - [Elastosis perforans serpiginosa. Considerations on the pathogenesis based on a
      typical case].
AB  - Elastosis perforans serpiginosa (EPS) is a rare entity belonging to the group of
      primary perforating dermatoses. A 13-year-old male patient with Down's syndrome
      developed reddish hyperkeratotic papules in a serpiginous and ellipsoid
      configuration on the face. Histological examination revealed transepidermal
      elimination of thick coarse elastic fibres from the papillary dermis. The dermal
      infiltrate showed an immunohistological pattern consistent with an acute cell
      mediated immune response. It consisted mainly of activated T-lymphocytes, with a
      predominance of CD4-positive cells. Considerable numbers of CD1-positive cells
      were also present. Inflammatory macrophages of the 27E10 phenotype were found in
      considerable numbers, whereas 25F9-positive resident macrophages were almost
      completely absent. The role of a cell-mediated immune response in the mechanism
      of transepithelial elimination is discussed.

PMID- 1358860
TI  - Quantification of in vivo binding of [3H]RX 821002 in rat brain: evaluation as a
      radioligand for central alpha 2-adrenoceptors.
AB  - On the basis of its established in vitro characteristics, [3H]RX 821002 was
      evaluated in rats as an in vivo radioligand for central alpha 2-adrenoceptors.
      Estimates for in vivo binding potential, obtained by compartmental analyses of
      time-radioactivity data, ranged between 1.9 for hypothalamus and 0.2 for
      cerebellum, with a regional distribution in brain which was similar to that
      observed in vitro. Selectivity and specificity of the signal were checked by
      predosing with either the alpha 2-antagonists, idazoxan or yohimbine, the alpha 2
      agonist, clonidine, or the alpha 1-antagonist, prazosin. Pretreatment of the rats
      with the selective neurotoxin, DSP-4, had no significant effect on [3H]RX 821002
      binding, suggesting that the majority of labelled sites were situated post
      junctionally. The studies indicate that [3H]RX 821002 can be used experimentally
      as an in vivo marker for central alpha 2-adrenoceptors. The size and rate of
      expression of the specific signal encourage the development and assessment of
      [11C]RX 821002 for clinical PET studies.

PMID- 1358862
TI  - Proceedings of the Urban Health Care Symposium II. June 2-4, 1991.

PMID- 1358861
TI  - [Chronic pancreatitis of the head of the pancreas in hyperplasia of the body and
      tail of the pancreas].
AB  - We report a case of chronic pancreatitis of the head of the pancreas complicated
      with insulin-requiring diabetes mellitus, in a 44-year-old woman with hypoplasia
      of the dorsal pancreas. Preoperative ultrasonography, computerized tomography and
      angiography revealed a calcifying retroperitoneal mass, which on explorative
      laparotomy proved to be a severe chronic pancreatitis of the head of the pancreas
      with a finding of abnormal visibility of the confluens venosum and absence of
      both the corpus and the tail of the pancreas. The postoperative course following
      pylorus-preserving duodenopancreatectomy was uneventful.

PMID- 1358864
TI  - Glutamate-like immunoreactivity in the leech central nervous system.
AB  - Using a monoclonal antibody for glutamate the distribution was determined of
      glutamate-like immunoreactive neurons in the leech central nervous system (CNS).
      Glutamate-like immunoreactive neurons (GINs) were found to be localized to the
      anterior portion of the leech CNS: in the first segmental ganglion and in the
      subesophageal ganglion. Exactly five pairs of GINs consistently reacted with the
      glutamate antibody. Two medial pairs of GINs were located in the subesophageal
      ganglion and shared several morphological characteristics with two medial pairs
      of GINs in the first segmental ganglion. An additional lateral pair of GINs was
      also located in segmental ganglion 1. A pair of glutamate-like immunoreactive
      neurons, which are potential homologs of the lateral pair of GINs in segmental
      ganglion 1, were occasionally observed in more posterior segmental ganglia along
      with a selective group of neuronal processes. Thus only a small, localized
      population of neurons in the leech CNS appears to use glutamate as their
      neurotransmitter.

PMID- 1358863
TI  - The evolution of proteinase substrates with special reference to
      dipeptidylpeptidase IV.
AB  - The design and development of specific substrates for proteolytic enzymes is
      reviewed. Particular attention is given to substrates containing the leaving
      groups 4-methoxy-2-naphthylamide (MNA) and 7-amino-4-trifluoromethylcoumarin
      (AFC). The MNA substrates are used for histochemical and cytochemical purposes,
      and they yield a coloured final reaction product when azo-coupled with a
      diazonium salt, an osmiophilic product for electron microscopy when coupled with
      hexazotized Pararosaniline, or a fluorescent final reaction product when coupled
      with 5-nitrosalicylaldehyde. AFC substrates are considerably more sensitive, and
      they yield the fluorescent product AFC after enzymatic cleavage of the substrate.
      AFC is not sufficiently water-insoluble to allow (intra)cellular localization,
      but AFC substrates are successfully used for incubations in microwells (Immu
      Probe technique) and for the demonstration of banding patterns after gel
      electrophoresis (enzyme-directed overlay membrane technique). The methods are
      discussed with the example of the elucidation of the role of dipeptidylpeptidase
      IV in autoimmune diseases.

PMID- 1358865
TI  - Alloimmunization to platelet antigen HPA-1a (PIA1) is strongly associated with
      both HLA-DRB3*0101 and HLA-DQB1*0201.
AB  - Antibodies to the platelet HPA-1a antigen can elicit in the newborn a condition
      known as neonatal alloimmune thrombocytopenic purpura (NAITP). Previous studies
      based on RFLP analysis showed that 100% of HPA-1a-negative women who produced
      anti-HPA-1a antibodies (responders) were HLA-DRw52a (DRB3*0101). However, this
      specificity could also be found in some HPA-1a-negative women not producing anti
      HPA-1a antibodies (nonresponders). We have analyzed in detail by PCR-SSOP the HLA
      DR, -DQ, and -DP loci of 36 responders and 10 nonresponders. We found that while
      the allele DRB3*0101 was present in the vast majority of responders (91%), there
      were exceptions. Furthermore, the DQB1*0201 allele was found to be present in
      almost all responders (94%), but again was also found in nonresponders. The risk
      of alloimmunization to HPA-1a in an HPA-1b homozygous mother significantly
      increases with the presence of either allele, the odds ratio being 39.7 for
      DQB1*0201 and 24.9 for DRB3*0101. Sequencing of exon 2 of these two alleles from
      responders indicated no sequence difference when compared with the consensus
      sequences. This indicates that they do not represent variants when compared with
      the same alleles found in some nonresponders.

PMID- 1358866
TI  - Nucleotide sequences of the HLA-DRw12 and DRw8 B1 chains from an Australian
      aborigine.
AB  - To gain a more detailed understanding of the molecular structure of the HLA genes
      in Australian aborigines, the polymorphic first-domain sequences of the DR B
      alleles were determined in an aborigine who was tissue typed as HLA-DRw8 and a
      probable DRw12; DRw52; DQw1,7. Both peripheral blood leukocytes and a
      lymphoblastoid cell line were reactive with the majority of DRw12-specific sera,
      but also with half of the DRw11-specific sera. With the use of primers specific
      for the conserved regions flanking the first domain, the polymerase chain
      reaction technique was used to amplify first-strand synthesis products prepared
      from the cell line. Two distinct DRB1 sequences were obtained. One was virtually
      identical to the reported DRw8,Dw8.3 sequence present in an Asian haplotype,
      differing only by a single silent nucleotide substitution at the third position
      of codon 36 (A to G). A second DRB allele was closely related to two recently
      published and nearly identical sequences for DRw12, with amino acid differences
      at positions 67 and 85 of the first domain. DRB RFLP studies on this cell line
      using the Taq I restriction enzyme indicated bands previously described for the
      DRw8 and DRw12 haplotypes.

PMID- 1358868
TI  - A new perspective on stress ulcer prophylaxis.
AB  - Gastric acid suppression by use of either antacids or histamine H2-receptor
      antagonist therapy is the mainstay of stress ulcer prophylaxis. Available
      evidence indicating an antimicrobial role for gastric acid calls for the
      reevaluation of gastric acid suppression. A pH of greater than 4.0 leads to
      bacterial overgrowth and colonization of the upper gastrointestinal tract which
      has been associated with nosocomial pneumonia, bacterial translocation from the
      gut, systemic sepsis, and multiple-organ failure. The availability of alternative
      therapy should discourage the routine use of acid-suppression therapy in the
      critically ill patient.

PMID- 1358867
TI  - Family study on HLA-DPB1 polymorphism: linkage analysis with HLA-DR/DQ and two
      "new" alleles.
AB  - An extensive family study on HLA-DPB1 was performed in 105 families living in
      northeastern Japan. In a linkage study between HLA-DPB1 and other HLA loci, five
      apparent recombinations between DPB1 and DR/DQ loci were observed. The
      recombination frequency (theta) with maximum probability was estimated to be
      0.017 by the lod score method. DPB1 allele and haplotype frequencies in unrelated
      parents were determined by direct counting. The most common allele was DPB1*0501
      with the frequency of 41.2% and the second was DPB1*0201 with 24.0%. Nine DPB1-DR
      and six DPB1-DQ haplotypes were in significant linkage disequilibrium. Seven
      kinds of extended haplotypes were observed to be over 1%, in which the most
      common haplotype A24-B52-DR15-DQ6-DPB1*0901 occurred at 6.0%. Moreover, we found
      two "new" DPB1 alleles in this study. The first one possesses a single base
      substitution from DPB1*0501 resulting in an amino acid change. The other is most
      likely to be formed by an intraexonic recombination between DPB1*0301 and
      DPB1*0501.

PMID- 1358869
TI  - Implications of psychopharmacological studies for the practice of psychoanalysis.
AB  - Over the past 35 years psychopharmacological developments have fueled major
      changes in the care of psychiatric patients. The most obvious of these are in two
      areas: (1) the control of symptoms not heretofore consistently treated
      effectively, such as the benefits of lithium in bipolar disorder, and (2) the
      shift toward reliance on medications rather than other forms of treatment. In
      this article I shall cover some of the implications of the second point, but will
      focus principally on other, less direct consequences of the development of
      specific pharmacotherapies for the practice of psychoanalysis. These areas are
      the enhanced importance of accurate diagnosis, the expansions of categories for
      which drugs are helpful, and the point, or framework, from which dynamic
      psychotherapies have their main indications.

PMID- 1358870
TI  - Diagnostic efficacy of serum alkaline phosphatase and gamma-glutamyltransferase
      in dogs with histologically confirmed hepatobiliary disease: 270 cases (1980
      1990).
AB  - The diagnostic efficacy of serum alkaline phosphatase (ALP) and gamma
      glutamyltransferase (GGT) activities was examined, using the records of 270 dogs
      initially suspected of having hepatobiliary disease on the basis of history,
      findings on physical examination, results of baseline screening tests, or any
      combination of these data. Histologic examination of hepatic tissue was performed
      in each dog. Sixty-three dogs did not have histologic evidence of hepatobiliary
      disease and served as the control group. On the basis of diagnosis, dogs were
      assigned to 1 of 8 groups: dogs with cirrhosis (n = 34), steroid hepatopathy (n =
      16), hepatic neoplasia (primary and secondary, n = 36), chronic hepatitis (n =
      14), chronic passive congestion (n = 5), hepatic necrosis (n = 17), portosystemic
      vascular anomaly (n = 35), and cholestasis (extrahepatic bile-duct obstruction
      and intrahepatic cholestasis, n = 50). Of the 207 dogs with hepatobiliary
      disease, 29 (14%) had normal ALP and GGT activities, 31 (15%) had normal ALP
      activity, and 112 (54%) had normal GGT activity. Of the 63 control dogs, 29 (46%)
      had normal serum ALP and GGT activities, 32 had normal ALP activity (ALP
      specificity, 51%), and 55 had normal GGT activity (GGT specificity, 87%). The
      specificity of ALP and GGT in parallel (positive result = result of either test
      abnormal) was 46%, and in series (positive result = results of both tests
      abnormal) was 91%. The highest median activities of ALP developed in dogs with
      cholestasis, steroid hepatopathy, chronic hepatitis, and hepatic necrosis. The
      highest median activities of GGT developed in dogs with steroid hepatopathy,
      cholestasis, and hepatic necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358871
TI  - Construction of a cDNA library from microdissected guinea pig organ of Corti.
AB  - Poly (A) RNA was isolated from microdissected guinea pig organ of Corti and
      converted into cDNA with RNase H- murine leukemia virus reverse transcriptase.
      After size fractionation, the cDNA was directionally ligated into the vector
      pSPORT 1 and the plasmids were transformed into DH10B E. coli via
      electroporation. The library was found to have 3.35 x 10(6) independent colonies
      with ten percent of the colonies lacking an insert. After checking 33 randomly
      selected colonies for inserts, the average insert size was 1218 base pairs,
      ranging from 3300 base pairs to 400 base pairs. The library was screened with a
      beta-actin oligonucleotide probe and 1.4% of the colonies contained an insert
      hybridizing to the probe.

PMID- 1358872
TI  - Effects of the beta-adrenergic agonist L644,969 on muscle protein turnover,
      endogenous proteinase activities, and meat tenderness in steers.
AB  - Eight MARC III composite (1/4 Hereford, 1/4 Angus, 1/4 Pinzgauer, and 1/4 Red
      Poll) steers weighing approximately 350 kg were fed 0 or 3 ppm of the beta
      adrenergic agonist L644,969 (Merck Sharp and Dohme Laboratories, Rahway, NJ) for
      6 wk in a high-concentrate diet. Feed efficiency was higher (P less than .05) in
      beta-adrenergic agonist-fed steers at 1, 3, 5, and 6 wk on trial. Average daily
      gain was greater (P less than .05) in beta-adrenergic agonist-fed steers at 3, 5,
      and 6 wk on treatment. Fractional degradation rate (percentage/day) of skeletal
      muscle myofibrillar protein was 27.1% lower (P less than .05) in beta-adrenergic
      agonist-fed steers at 3 wk on trial. Fractional accretion rate (percentage/day)
      of skeletal muscle myofibrillar protein in beta-adrenergic agonist-fed steers was
      higher (P less than .05) at 1, 3, 5, and 6 wk on trial. The beta-adrenergic
      agonist-fed steers had heavier (P less than .05) carcasses (9.6%), larger (P less
      than .05) longissimus muscle areas (24.3%), and lower (P less than .05) USDA
      yield grades (43.8%). Marbling degree, USDA quality grade, kidney, pelvic, and
      heart fat percentage, and 12th rib fat thickness were not different (P greater
      than .05). Calpastatin activity was higher (P less than .05) in muscle from the
      beta-adrenergic agonist-fed steers at 0 and 7 d postmortem. There were no
      differences (P greater than .05) in mu- or m-calpain or in cathepsins B or B+L or
      cystatin(s) between beta-adrenergic agonist-fed and control steers.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1358873
TI  - Production of Neisseria gonorrhoeae pili (fimbriae) in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa K/2PfS, when transformed with an expression plasmid
      harboring the pilin gene (pilE1) of Neisseria gonorrhoeae MS11, was able to
      express and assemble gonococcal pilin monomers into surface-associated pili, as
      judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      immunoblotting, and immunoelectron microscopy. Concomitant with the expression of
      gonococcal pili in P. aeruginosa was the virtual loss of production of P.
      aeruginosa K/2PfS pili normally associated with the host cell.

PMID- 1358875
TI  - Structural comparison of urease and a GroEL analog from Helicobacter pylori.
AB  - Electron microscopy of purified protein preparations indicated that Helicobacter
      pylori urease consisted of circular particles that are 13 nm in diameter, some of
      which showed indications of threefold rotational symmetry. A GroEL analog of H.
      pylori (Hp60K) appeared as a disc-shaped molecule with a diameter similar to that
      of urease but possessed sevenfold rotational symmetry. In a side-view projection,
      Hp60K appeared as two or four discs stacked side by side.

PMID- 1358874
TI  - The lethal phenotype caused by null mutations in the Escherichia coli htrB gene
      is suppressed by mutations in the accBC operon, encoding two subunits of acetyl
      coenzyme A carboxylase.
AB  - Insertion mutations in the Escherichia coli htrB gene result in the unique
      phenotype of not affecting growth at temperatures below 32.5 degrees C but
      leading to a loss of viability at temperatures above this in rich media. When
      htrB bacteria growing in rich media were shifted to the nonpermissive temperature
      of 42 degrees C, they continued to grow at a rate similar to that at 30 degrees C
      but they produced phospholipids at the rate required for growth at 42 degrees C.
      This led to the accumulation of more than twice as much phospholipid per
      milligram of protein compared with that in wild-type bacteria. Consistent with
      HtrB playing a role in phospholipid biosynthesis, one complementation group of
      spontaneously arising mutations that suppressed htrB-induced lethality were
      mapped to the accBC operon. This operon codes for the biotin carboxyl carrier
      protein and biotin carboxylase subunits of the acetyl coenzyme A carboxylase
      enzyme complex, which catalyzes the first step in fatty acid biosynthesis. Four
      suppressor mutations mapped to this operon. Two alleles were identified as
      mutations in the accC gene, the third allele was identified as a mutation in the
      accB gene, and the fourth allele was shown to be an insertion of an IS1
      transposable element in the promoter region of the operon, resulting in reduced
      transcription. The suppressor mutations caused a decrease in the rate of
      phospholipid biosynthesis, restoring the balance between the biosynthesis of
      phospholipids and growth rate, thus enabling htrB bacteria to grow at high
      temperatures.

PMID- 1358876
TI  - Clozapine treatment of psychosis in Parkinson's disease: a report of five
      consecutive cases.
AB  - BACKGROUND: Clozapine has gained acceptance as an antipsychotic in treatment
      resistant schizophrenia. Its low propensity to induce extrapyramidal side effects
      makes clozapine an attractive treatment for patients with Parkinson's disease and
      dopaminomimetic psychosis. Recent evidence demonstrates that Parkinson's patients
      are exquisitely sensitive to both the antipsychotic and the potential
      extrapyramidal effects of clozapine. The uncontrolled studies suggest that low
      dose clozapine may be efficacious in this population. The dose range, side effect
      profiles, and length of treatment varied in these reports. METHOD: We report our
      experience with five patients with Parkinson's disease and psychosis who were
      treated with clozapine in an open trial. RESULTS: Three patients were
      successfully treated with clozapine (25-100 mg/day, mean = 66.7 mg) without
      worsening their parkinsonism. Adverse effects unrelated to the motor disability
      required discontinuation of clozapine in the other two patients. At 1- to 2-year
      follow-up, each patient had required increased dosages of clozapine (75-150
      mg/day, mean = 125 mg) for continued management of their psychosis and
      parkinsonism. The higher dose range was well tolerated. CONCLUSION: These results
      suggest that clozapine may effectively treat psychosis in Parkinson's disease.

PMID- 1358877
TI  - Reaction mechanism of glutamate racemase, a pyridoxal phosphate-independent amino
      acid racemase.
AB  - Glutamate racemase of Pediococcus pentosaceus contained no cofactor, and was
      completely inactivated by a thiol reagent. The role of a cysteine residue in the
      enzyme reaction was studied by chemical modification. The modification of this
      cysteine residue resulted in a concomitant loss of activity. DL-Glutamate
      protected the enzyme from inactivation. The inactivated enzyme was reactivated by
      addition of dithiothreitol. The racemization in 2H2O showed an overshoot in the
      optical rotation of glutamate before the substrate was completely racemized. This
      indicates that the removal of alpha-hydrogen is the rate determining step. During
      the racemization of D- or L-glutamate in 3H2O, tritium was incorporated
      preferentially into the product. Glutamate is racemized by the enzyme probably
      through a two base mechanism.

PMID- 1358878
TI  - Rat liver dipeptidylpeptidase IV contains competing apical and basolateral
      targeting information.
AB  - Madin-Darby canine kidney (MDCK) cells deliver endogenous apical and basolateral
      proteins directly to the appropriate domains. We are investigating the molecular
      signals on a model plasma membrane hydrolase, dipeptidylpeptidase IV (DPPIV).
      Most newly synthesized rat liver DPPIV is delivered directly to the apical
      surface of transfected MDCK cells; however, about 20% is delivered first to the
      basolateral surface and reaches the apical surface via transcytosis (Casanova, J.
      E., Mishumi, Y., Ikehara, Y., Hubbard, A. L., and Mostov, K. E. (1991) J. Biol.
      Chem. 266, 24428-24432). A soluble form of DPPIV (solDPPIV) containing only the
      lumenal domain of the protein was efficiently transported and secreted by stably
      transfected MDCK cells. If this domain contains apical sorting information, we
      would expect 80% of the soluble protein to be secreted apically. Surprisingly,
      95% of the secreted solDPPIV was found in the apical medium. The high efficiency
      of apical secretion suggested that the transmembrane domain and cytoplasmic tail
      of DPPIV might contain competing basolateral targeting information. To test this
      hypothesis, we investigated the trafficking of a chimera in which the cytoplasmic
      tail and transmembrane domains of DPPIV were joined to lysozyme, an exogenous
      protein which should not contain sorting information. This protein was delivered
      predominantly to the basolateral surface. Our results suggest that the lumenal
      domain of DPPIV carries dominant apical sorting information while the
      transmembrane domain and cytoplasmic tail of the molecule contains competing
      basolateral sorting information.

PMID- 1358879
TI  - Activation of Ca2+/calmodulin-dependent protein kinase II and protein kinase C by
      glutamate in cultured rat hippocampal neurons.
AB  - In cultured rat hippocampal neurons, glutamate elevated the Ca(2+)-independent
      activity of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) through
      autophosphorylation when the neurons were incubated in Mg(2+)-free buffer, and
      this response was blocked by specific antagonists of the N-methyl-D-aspartate
      (NMDA) receptor. In addition, glutamate stimulated the transient translocation of
      protein kinase C (PKC) from the cytosol to the membrane fraction. This effect was
      not blocked by NMDA receptor antagonists but was partially blocked by DL-2-amino
      3-phosphonopropionate. Quisqualate or trans-1-amoinocyclopentane-trans1,3
      dicarboxylate produced a similar effect on the translocation of PKC. In the
      experiments with 32P-labeled cells, the phosphorylation of microtuble-associated
      protein 2 and synapsin I, as well as autophosphorylation of CaM kinase II, were
      found to be stimulated by exposure to glutamate. These results suggest that
      glutamate can activate CaM kinase II through the ionotropic NMDA receptor, which
      in turn increases the phosphorylation of microtuble-associated protein 2 and
      synapsin I. PKC was activated through the metabotropic glutamate receptor in the
      hippocampal neurons.

PMID- 1358880
TI  - A retinoic acid-inducible mRNA from human erythroleukemia cells encodes a novel
      tissue transglutaminase homologue.
AB  - A 1.9-kilobase (kb) cDNA for a new transglutaminase protein has been cloned and
      sequenced from retinoic acid-induced human erythroleukemia (HEL) cells. Full
      length cDNA analysis reveals an open reading frame coding for a polypeptide of
      548 amino acid residues with a molecular weight of 61,740. The deduced amino acid
      sequence exhibited 98% identity to the human cellular transglutaminase sequence.
      The cysteine at position 277 in the active site and the putative Ca(2+)-binding
      pocket at residues 446-453 of cellular transglutaminase are conserved. Such
      evidence predicts that the encoded protein product is likely to be a
      transglutaminase homologue (TGase-H). Immunoprecipitation of the in vitro
      translation products from a synthetic TGase-H mRNA and from total protein of
      cultured erythroleukemia HEL cells revealed a protein with a molecular weight of
      63,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Northern
      blot analysis of HEL cells and normal human fibroblast cells WI-38 using a
      cellular TGase probe detected the 1.9- and 4.0-kb RNA species at a relative
      abundance of 1:3 and 1:7, respectively. The 3'-end of the human cellular
      transglutaminase mRNA was also cloned and sequenced to allow comparison to the 3'
      end of TGase-H reported here. This new piece gives a full length of 4012
      nucleotides (4.0 kb) for human cellular transglutaminase. Comparison of the 5'
      end (bases 1-1747) of the 1.9- and 4.0-kb cDNA sequences revealed a very high
      degree of identity. Beginning with base 1748, the sequences diverge showing no
      homology. The divergence point correlates with known intron-exon consensus
      boundaries indicative of alternative splicing.

PMID- 1358882
TI  - Expression of plant chaperonin-60 genes in Escherichia coli.
AB  - We have examined the expression in Escherichia coli of genes encoding a plant
      chloroplast molecular chaperone, chaperonin-60. Purified plant chaperonin-60 is
      distinct in that it contains two polypeptides, p60cpn-60 alpha and p60cpn-60
      beta, which have divergent amino acid sequences (Hemmingsen, S. M., and Ellis, R.
      J. (1986) Plant Physiol. 80, 269-276; Martel, R., Cloney, L. P., Pelcher, L. E.,
      and Hemmingsen, S. M. (1990) Gene (Amst.) 94, 181-187). The precise polypeptide
      composition(s) of the active tetradecameric specie(s) (cpn60(14)) has not been
      determined. Genes encoding the mature forms of the Brassica napus chaperonin
      polypeptides have been expressed separately and in combination in E. coli to
      produce three novel strains: alpha, beta, and alpha beta. The plant cpn60
      polypeptides accumulated in soluble forms and to similar high levels in each.
      There was no conclusive evidence that p60cpn-60 alpha assembled into cpn60(14)
      species in alpha cells. In beta and alpha beta cells, the plant gene products
      assembled efficiently into cpn60(14) species. Thus, the assembly of p60cpn-60
      alpha required the presence of p60cpn-60 beta, whereas the assembly of p60cpn-60
      beta could occur in the absence of p60cpn-60 alpha. Significant proportions of
      the endogenous groEL polypeptides were not assembled into tetradecameric groEL14
      in beta and alpha beta cells. Analysis of the tetradecameric species that did
      form indicated the presence of novel hybrid cpn6014 species that contained both
      plant and bacterial cpn60 polypeptides.

PMID- 1358881
TI  - Oncogenic ras induces an inhibitor of double-stranded RNA-dependent eukaryotic
      initiation factor 2 alpha-kinase activation.
AB  - The interferon-inducible 68-kDa dsRNA-dependent eIF2 alpha-kinase (dsI) is a
      potent cellular antiviral enzyme which is activated by autophosphorylation in
      response to double-stranded RNA (dsRNA). Activated dsI has also been implicated
      as a second messenger for gene induction by platelet-derived growth factor (PDGF)
      and interferon (IFN). We have shown previously that introduction of a
      transforming ras gene into BALB/c-3T3 fibroblasts blocks induction of responsive
      genes by PDGF and IFN. We therefore investigated the effect of transforming ras
      genes on dsI activity in these cells. We report here that dsRNA-mediated
      activation of dsI is blocked in v-ras-containing cells in a manner specific to
      ras and not attributable to the transformed phenotype since: 1) a dexamethasone
      inducible v-Ha-ras gene produced the effect within 18 h of induction; 2)
      morphologic reversion of ras-transformed cells with cAMP or the Krev-1 gene
      restored potential for dsI activation; and 3) transformation by v-mos or v-abl
      had no effect on dsI activation. Latent dsI levels were unaffected by v-ras. A
      heat-sensitive dsI inhibitory activity could be demonstrated in v-ras-containing
      cells which functioned in trans when mixed with untransformed cell extracts prior
      to stimulation with dsRNA. The inhibitory activity, which was destroyed by phenol
      chloroform extraction, did not bind dsRNA.

PMID- 1358883
TI  - Assessment of plant chaperonin-60 gene function in Escherichia coli.
AB  - Brassica napus chaperonin-60 alpha and chaperonin-60 beta genes expressed
      separately and in combination produce three novel Escherichia coli strains:
      alpha, beta, and alpha beta. In beta and alpha beta cells, the plant gene
      products assemble efficiently into tetradecameric cpn60(14) species, including
      novel hybrids containing both bacterial and plant gene products. The levels of
      authentic groEL14 are reduced in these cells (Cloney, L. P., Wu, H. B., and
      Hemmingsen, S. M. (1992) J. Biol. Chem. 267, 23327-23332). The assembly of
      cyanobacterial ribulose-P2 carboxylase (rubisco) in E. coli requires the
      activities of the endogenous chaperonin proteins. Furthermore, the extent to
      which assembly occurs is limited by the normal levels of expression of the groE
      operon (Goloubinoff, P., Gatenby, A. A., and Lorimer, G. H. (1989) Nature 337, 44
      47). We have now monitored the accumulation of cyanobacterial rubisco in E. coli
      alpha, beta, and alpha beta cells to assess the activity of the plant cpn60 gene
      products and effects on endogenous chaperonin functions. Expression of cpn-60
      alpha alone did not enhance rubisco assembly, which is consistent with our
      previous observation that p60cpn-60 alpha required the presence of p60cpn-60 beta
      for assembly into cpn60(14) species. In contrast, expression of cpn-60 beta alone
      resulted in markedly enhanced rubisco assembly in cells that accumulated normal
      levels of both endogenous chaperonin polypeptides (groEL and groES). This
      demonstrates that assembled p60cpn-60 beta is functional as a chaperonin in E.
      coli. Co-expression of cpn-60 alpha and cpn-60 beta in cells with normal levels
      of expression of groES and groEL suppressed rubisco assembly. Increased
      expression of groES in cells in which cpn-60 alpha and cpn-60 beta were co
      expressed relieved this suppression and resulted in enhanced rubisco assembly.
      Implications with respect to dependence of chloroplast cpn60 function on cpn10
      are discussed.

PMID- 1358884
TI  - A human polyadenylation factor is a G protein beta-subunit homologue.
AB  - Cleavage stimulation factor (CstF) is one of the multiple factors required for
      polyadenylation of mammalian pre-mRNAs in vitro. We have shown previously that
      this factor is composed of three distinct subunits of 77, 64, and 50 kDa, and
      that the 64-kDa subunit can be UV-cross-linked to RNA in a polyadenylation signal
      (AAUAAA)-dependent manner. By molecular cloning, the 64-kDa subunit was shown to
      contain a ribonucleoprotein-type RNA binding domain and a novel repeat structure.
      To study the functions of the other subunits, we have now isolated cDNAs encoding
      the 50-kDa subunit of human CstF. This subunit shares extensive homology with
      mammalian G protein beta-subunits and has a characteristic repeat structure
      (transducin repeat), in which an approximately 44-amino acid-long sequence is
      repeated seven times. To our knowledge, the 50-kDa subunit is the first example
      of a functional beta-subunit-like protein in vertebrates. Possible roles of the
      transducin repeat, both in CstF function specifically and in other beta-subunit
      homologues more generally, are discussed.

PMID- 1358885
TI  - Involvement of sequences near both amino and carboxyl termini in the rapid
      intracellular degradation of tyrosine aminotransferase.
AB  - The degradation of rat liver tyrosine aminotransferase has been studied after
      transfection of suitable expression vectors into mammalian cells in culture. A
      normal rapid rate of degradation (half-life about 6 h) was observed in cells
      under stable transfection conditions. However, the higher enzyme levels produced
      during transient transfections or after amplification with methotrexate caused
      the apparent half-life of degradation to increase substantially. Analysis of
      expression in Chinese hamster ovary (CHO)-DG44 cells from vectors with deletions
      near either end of the tyrosine aminotransferase coding sequence showed that
      approximately the first 40 and the last 12 amino acid residues are not required
      to obtain normal catalytic function. When catalytically active deletion mutants
      were examined for effects on tyrosine aminotransferase degradation in stably
      transfected CHO-DG44 cell populations, short sequences near each end of the
      protein were found to be necessary for rapid degradation. The required sequence
      near the amino terminus is located between amino acids 30 and 40 and includes the
      highly basic region RKKGRKAR, a potential ubiquitin attachment site. The other
      essential sequence (EECDK) is located at the very COOH terminus of the 454-amino
      acid chain and is part of an acidic domain rich in cysteines and having PEST
      characteristics (rich in Pro, Glu, and Thr). Ser448, a potential casein kinase II
      phosphorylation site, is not required for activity or rapid degradation of
      tyrosine aminotransferase. No correlation was observed between the intracellular
      degradation rates of the various mutant proteins and their heat stabilities in
      vitro.

PMID- 1358886
TI  - Factors determining the specificity of signal transduction by guanine nucleotide
      binding protein-coupled receptors. III. Coupling of alpha 2-adrenergic receptor
      subtypes in a cell type-specific manner.
AB  - A number of diverse signaling pathways can be activated by G-protein coupled
      receptors. However, the factors involved in selection of a particular
      transduction pathway by a single receptor are not well understood. We are
      attempting to address this issue utilizing the alpha 2-adrenergic receptor (alpha
      2-AR) subfamily as a representative model system. In this report, we demonstrate
      that the cellular response mediated by an alpha 2-AR subtype is cell-specific and
      thus depends on its environment. Receptor coupling to adenylylcyclase was
      determined following stable expression of the rat alpha 2B- and alpha 2D-AR
      subtypes in three functionally distinct cell types (NIH-3T3 fibroblasts, DDT1 MF
      2 smooth muscle cells, and the pheochromocytoma cell line PC-12). When the
      receptor subtype gene is expressed in NIH-3T3 and DDT1 MF-2 cells, receptor
      activation inhibits basal and forskolin-induced increases in cellular cAMP.
      However, in PC-12 transfectants the same receptor subtype actually increases
      basal cAMP and augments the effect of forskolin. Potentiation of the forskolin
      effect in PC-12 cells is insensitive to pertussis toxin but is blocked by loading
      the cells with BAPTA (bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid)
      which minimizes changes in Ca2+i by calcium chelation. These data and the
      functional demonstration of a Ca2+/calmodulin-sensitive adenylylcyclase in PC-12
      but not NIH-3T3 and DDT1 MF-2 cells, suggests that the cell-specific effects of
      epinephrine are due to receptor coupling to both different G-proteins and types
      of adenylylcyclase.

PMID- 1358887
TI  - Beta-adrenergic agonists that down-regulate receptor mRNA up-regulate a M(r)
      35,000 protein(s) that selectively binds to beta-adrenergic receptor mRNAs.
AB  - In an effort to explore the molecular basis for agonist-induced destabilization
      of beta-adrenergic receptor mRNA, we investigated the nature of RNA-binding
      proteins both in untreated and agonist-treated DDT1-MF2 smooth muscle cells.
      Messenger RNAs for the alpha 1b-, beta 1-, and beta 2-adrenergic receptors as
      well as for beta-globin were transcribed in vitro, incubated with cytosolic
      fractions, covalently cross-linked by short-wave UV light, and analyzed by SDS
      polyacrylamide gel electrophoresis. A prominent M(r) 35,000 radiolabeled
      protein(s) with the following characteristics was identified: (i) binds
      selectively to beta 1- and beta 2-adrenergic receptor mRNAs, both of which
      undergo agonist-induced down-regulation; (ii) does not bind to either alpha 1b
      adrenergic receptor mRNA, which does not undergo agonist induced down-regulation,
      or to beta-globin mRNA; (iii) displays binding to beta 2-adrenergic receptor mRNA
      that is selectively competed by poly(U) RNA, but not poly(A), -(C), or -(G) RNA;
      and (iv) displays binding to receptor mRNA that can be competed by RNA harboring
      destabilizer sequences that are AU-rich and AUUUA pentamer-rich. The abundance of
      the M(r) 35,000 RNA-binding protein selective for beta-adrenergic receptor
      message, a factor we term beta ARB protein, varies inversely with the level of
      receptor mRNA, being induced by agonists that down-regulate receptor mRNA.

PMID- 1358888
TI  - Regulation of ADP-ribosylation factor (ARF) expression. Cross-species
      conservation of the developmental and tissue-specific alternative polyadenylation
      of ARF 4 mRNA.
AB  - ADP-ribosylation factors (ARFs), approximately 20-kDa guanine nucleotide-binding
      proteins, are involved in protein trafficking and enhance cholera toxin ADP
      ribosyltransferase activity. Expression of six ARF genes was examined in
      mammalian tissues; only ARF 4 mRNA was detected in rat testis in forms
      considerably shorter than those in other tissues. Testis-specific expression of
      short forms of ARF 4 mRNA was observed in several mammalian species. On Northern
      analysis of the developmental expression of rat ARF 4 mRNA, appearance of the
      shorter species was consistent with its involvement in a late stage of
      spermatogenesis. Sequences of products of rapid amplification of cDNA ends (RACE
      polymerase chain reaction) of rat ARF 4 mRNA revealed that different mRNAs
      resulted from the use of three polyadenylation signals, one AUUAAA and two
      AAUAAA. Sequences of 3'-untranslated regions of rat and human ARF 4 mRNA were
      very similar with identical polyadenylation signals at similar positions. Of the
      ARF 4 mRNAs identified by RACE-PCR, with sizes of 1.1, 1.3, and 1.8 kb, the 1.1
      kb mRNA was predominant in adult testis. By in situ hybridization, the 1.1-kb
      mRNA was identified primarily in mature sperm, consistent with the developmental
      studies. Shorter mRNAs, thought to be more stable, may compensate for cessation
      of transcription at late stages of spermatogenesis.

PMID- 1358889
TI  - Functional involvement of alpha 1- and alpha 2-adrenoceptors in 86Rb efflux from
      liver slices and lipolysis in guinea-pig isolated adipocytes.
AB  - 1. The application of an alpha 1-adrenoceptor agonist, amidephrine, to guinea-pig
      liver slices increases glucose release and 86Rb efflux. Since prazosin was more
      potent than yohimbine in inhibiting both responses, alpha 1-adrenoceptors seem to
      be involved in the effects evoked by the agonist. 2. Clonidine (an alpha 2
      adrenoceptor agonist) at doses unable to activate liver glycogenolysis increased
      86Rb release and potentiated isoprenaline in promoting 86Rb efflux. Since
      yohimbine antagonized clonidine in promoting 86Rb efflux, alpha 2-adrenoceptors
      also seem to control plasmalemmal permeability to 86Rb. 3. The liver slice
      responses resulting from alpha 1- and alpha 2-adrenoceptor stimulation required
      extracellular calcium. Calcium absence or the administration of D-600 attenuated
      the effects of amidephrine on glucose release and 86Rb outflow and Ca2+ excess re
      established both responses. D-600 and apamin blocked clonidine-induced 86Rb
      efflux, suggesting that alpha 2-adrenoceptor stimulation activates calcium
      dependent K+ channels. 4. alpha 2-adrenoceptors do not appear to mediate
      antilipolytic effects in guinea-pig fat cells.

PMID- 1358890
TI  - Effect of quinpirole on neurogenic vasoconstriction in the in situ autoperfused
      hindquarters and renal vascular beds of the rat.
AB  - 1. The effects of local administration of quinpirole were studied in the in situ
      autoperfused hindquarters and renal vascular beds, in order to assess whether
      presynaptic dopamine receptors in these vascular systems could play a role in the
      hypotensive effect of this agonist. 2. In both preparations, local injection of
      quinpirole did not alter perfusion pressure, but reduced the pressor response to
      electrical stimulation of the sympathetic innervation. Increases in perfusion
      induced by local administration of noradrenaline were not altered by quinpirole.
      3. The inhibitory effect of quinpirole on the stimulation-evoked pressor
      responses was completely antagonized by intravenous administration of the DA2
      receptor antagonist domperidone (0.5 mg kg-1) but not by the DA1-receptor
      antagonist SCH 23390 (0.3 mg kg-1) or the alpha 2-adrenoceptor antagonist
      idazoxan (0.3 mg kg-1). 4. The results indicate that quinpirole inhibits neurally
      induced pressor responses in the autoperfused hindquarters and renal vascular
      beds of the rat by stimulation of presynaptic dopamine receptors. These receptors
      may be involved in the hypotensive action of quinpirole in the rat.

PMID- 1358891
TI  - Biphasic dose-dependent effects of dopamine and involvement of dopamine
      autoreceptors on intra-ocular pressure in the rabbit.
AB  - 1. This work was conducted to provide new data concerning the possible dose
      dependent activity of dopamine (DA) after ocular instillation. Experiments were
      done in rabbits with normal intraocular pressure (IOP), or after transitory
      induced ocular hypertension in water-loaded animals. 2. In ocular normotensive
      animals, a biphasic dose-dependent activity is observed, with no significant
      effect for 0.001% and 0.003% DA, a decrease in IOP after 0.005% and 0.01% DA
      instillation, then an important increase in IOP at concentrations from 0.05%
      onwards. 3. During transitory ocular hypertension, this phenomenon was confirmed,
      with a marked ocular hypotensive activity for 0.01% DA, no effect after 0.005%
      DA, then an important ocular hypertension with 0.05% and 0.5% DA as compared to
      the control group (0.9% NaCl). 4. An immediate and similar ocular hypertensive
      effect with DA could be reproduced by a subsequent instillation at high
      concentration (1%), while the hypotensive activity induced at low concentration
      (0.01%) is followed by a long-lasting refractory period (about 18 h). 5. Such a
      dose-dependent biphasic effect was also observed with N-methyl-dopamine (NMDA)
      after ocular instillation. The effects of instilled dopaminergic compounds were
      tested and ocular hypotensive activities of the S(-)enantiomer of the DA
      analogues 3-(3-hydroxyphenyl)-N-propylpiperidine (3-PPP), and of thiothixene
      (TIX) were also demonstrated. 6. The possible relationships to DA1 and DA2
      receptors of the dual effect is discussed.

PMID- 1358892
TI  - Decreased tissue reaction to bioprosthetic heart valve material after L-glutamic
      acid treatment. A morphological study.
AB  - Degenerative alterations of two different glutaraldehyde (GA)-fixed bioprosthetic
      heart valve materials were investigated in subcutaneous rat implants: Bovine
      pericardium, prepared according to clinically used bioprosthetic heart valve
      material (BHV) was compared to alternatively preserved pericardium (APHV), which
      was fixed in GA and treated with L-glutamic acid. Following 63 days of
      subcutaneous implantation, calcification of APHV implants was significantly lower
      as compared to BHV implants (13 +/- 6 versus 158 +/- 18 micrograms Ca/mg dry
      weight tissue; p less than 0.05). In BHV implants ultrastructural investigations
      showed nucleation of plate-shaped hydroxyapatite crystals at the surface of
      collagen fibrils and in remnants of connective tissue cells; no signs of
      calcification could be detected in APHV implants. The time-course of the
      inflammatory reaction was determined by quantification of immunohistochemical
      stained mononuclear host-cells invading the implants. In both preparation groups
      inflammatory reaction reached maximum 42 days after implantation. However,
      infiltration rate of inflammatory cells was markedly decreased in APHVs as
      compared to BHVs (p less than 0.05).

PMID- 1358893
TI  - Argyrophilic nucleolar organizer region counts and proliferating cell nuclear
      antigen scores are two reliable indicators of survival in pharyngeal carcinoma.
AB  - The proliferative activity of pharyngeal carcinoma has been investigated by means
      of monoclonal antibody PC10 against proliferating cell nuclear antigen
      (PCNA/cyclin) and argyrophilic nucleolar organizer region (AgNOR) analysis in
      formalin-fixed, paraffin-embedded biopsies from 45 primary squamous and
      undifferentiated carcinomas, prior to therapy. The correlation between AgNOR
      counts and PCNA(PC10) scores was highly significant (r = 0.73; P < 0.0001) as
      determined by Pearson's correlation coefficient. Moreover, the univariate Kaplan
      Meier survival analysis showed a significant correlation between 3- and 5-year
      survival rates and the mean AgNOR number per tumour cell (P = 0.0003) or the
      percentage of PCNA(PC10)-positive cells (P = 0.0001). Our results indicate that
      both AgNOR counts and PCNA(PC10) scores are reliable markers of the proliferative
      activity of pharyngeal carcinoma in small, routinely processed biopsies, in which
      they can allow simultaneous evaluation of the histology and tumour cell kinetics.

PMID- 1358894
TI  - Adriamycin binding assay: a valuable chemosensitivity test in human osteosarcoma.
AB  - The reliability of a simple method evaluating the pattern of subcellular binding
      of Adriamycin (Adriamycin binding assay, ABA) as an index of sensitivity was
      demonstrated in different primary cultures and in sensitive and resistant cell
      lines of human osteosarcoma. After exposure to Adriamycin (10 micrograms/ml for
      30 min at 37 degrees C), living sensitive cells showed selective intranuclear
      uptake of the drug, whereas in resistant cells no distinct subcellular
      distribution was observed. The binding pattern of Adriamycin in sensitive and in
      highly resistant cells was inversely related to the expression of P-glycoprotein.
      However, low levels of resistance in vitro, not detectable by increased levels of
      expression of P-glycoprotein, were revealed by ABA. The use of ABA in combination
      with the estimate of P-glycoprotein expression is recommended in clinical
      practice as an accurate means for predicting the sensitivity of osteosarcoma to
      Adriamycin.

PMID- 1358895
TI  - Sialosylated Lewis chi expression in CD30-positive anaplastic large-cell
      lymphomas.
AB  - The expression of sialosylated Lewis chi (SLEX), a ligand for endothelial
      leukocyte adhesion molecule 1 in malignant lymphomas, was immunohistochemically
      examined, using the monoclonal antibody, CSLEX1, which specifically reacts with
      SLEX. It was expressed in 6 out of 64 non-Hodgkin's lymphomas, which consisted of
      1 nasal large-cell lymphoma and 5 of 8 (62%) Ki-1-positive anaplastic large-cell
      lymphomas (ALCL). One nasal lymphoma positive for SLEX co-expressed a T cell
      marker, cluster of differentiation (CD) 5, and natural killer (NK) cell markers
      such as CD56 and CD16, indicating that SLEX+ nasal lymphoma cells are possibly
      malignant counterparts of SLEX+ NK cells. SLEX did not react with 30 B cell
      lymphomas or most Hodgkin's disease lymphomas, though it did with one lymphocyte
      predominance type. Although SLEX+ ALCL exhibit T cell markers in some cases, some
      ALCL expressing SLEX may represent histiocytic differentiation of the neoplastic
      cells. The lymphoma cells of ALCL were preferentially positive for SLEX, in
      contrast to Hodgkin's disease cells, and thus CSLEX1 in conjunction with CD30 and
      CD15 should be of use for analyzing and making differential diagnoses of routine
      paraffin-embedded sections of ALCL.

PMID- 1358896
TI  - Clathrin assembly protein AP-2 induces aggregation of membrane vesicles: a
      possible role for AP-2 in endosome formation.
AB  - We have examined the in vitro behavior of clathrin-coated vesicles that have been
      stripped of their surface coats such that the majority of the clathrin is removed
      but substantial amounts of clathrin assembly proteins (AP) remain membrane
      associated. Aggregation of these stripped coated vesicles (s-CV) is observed when
      they are placed under conditions that approximate the pH and ionic strength of
      the cell interior (pH 7.2, approximately 100 mM salt). This s-CV aggregation
      reaction is rapid (t1/2 < or = 0.5 min), independent of temperature within a
      range of 4-37 degrees C, and unaffected by ATP, guanosine-5'-O-(3-thiophosphate),
      and in particular EGTA, distinguishing it from Ca(2+)-dependent membrane
      aggregation reactions. The process is driven by the action of membrane-associated
      AP molecules since partial proteolysis results in a full loss of activity and
      since aggregation is abolished by pretreatment of the s-CVs with a monoclonal
      antibody that reacts with the alpha subunit of AP-2. However, vesicle aggregation
      is not inhibited by PPPi, indicating that the previously characterized
      polyphosphate-sensitive AP-2 self-association is not responsible for the
      reaction. The vesicle aggregation reaction can be reconstituted: liposomes of
      phospholipid composition approximating that found on the cytoplasmic surfaces of
      the plasma membrane and of coated vesicles (70% L-alpha-phosphatidylethanolamine
      (type I-A), 15% L-alpha-phosphatidyl-L-serine, and 15% L-alpha
      phosphatidylinositol) aggregated after addition of AP-2, but not of AP-1, AP-3
      (AP180), or pure clathrin triskelions. Aggregation of liposomes is abolished by
      limited proteolysis of AP-2 with trypsin. In addition, a highly purified AP-2
      alpha preparation devoid of beta causes liposome aggregation, whereas pure beta
      subunit does not, consistent with results obtained in the s-CV assay which also
      indicate the involvement of the alpha subunit. Using a fluorescence energy
      transfer assay we show that AP-2 does not cause fusion of liposomes under
      physiological solution conditions. However, since the fusion of membranes
      necessarily requires the close opposition of the two participating bilayers, the
      AP-2-dependent vesicle aggregation events that we have identified may represent
      an initial step in the formation and fusion of endosomes that occur subsequent to
      endocytosis and clathrin uncoating in vivo.

PMID- 1358898
TI  - Extracellular ATP and ADP stimulate proliferation of porcine aortic smooth muscle
      cells.
AB  - The mitogenic effect of extracellular ATP on porcine aortic smooth muscle cells
      (SMC) was examined. Stimulation of [3H]thymidine incorporation by ATP was dose
      dependent; the maximal effect was obtained at 100 microM. ATP acted
      synergistically with insulin, IGF-1, EGF, PDGF, and various other mitogens.
      Incorporation of [3H]thymidine was correlated with the fraction of [3H]thymidine
      labeled nuclei and changes in cell counts. The stimulation of proliferation was
      also determined by measurement of cellular DNA using bisbenzamide and by
      following the increase of mitochondrial dehydrogenase protein. The effect of ATP
      was not due to hydrolysis to adenosine, which shows synergism with ATP. ATP acted
      as a competence factor. The mitogenic effect of ATP, but not adenosine, was
      further increased by lysophosphatidate, phosphatidic acid, or norepinephrine. The
      inhibitor of adenosine deaminase, EHNA, stimulated the effect of adenosine but
      not ATP. The adenosine receptor antagonist theophylline depressed adenosine
      induced mitogenesis. ADP and the non-hydrolyzable analogue adenosine 5'-[beta,
      gamma-imido]triphosphate (AMP-PNP) were equally mitogenic. Thus extracellular ATP
      stimulated mitogenesis of SMC via P2Y purinoceptors. The mechanism of ATP acting
      as a mitogen in SMC was further explored. Extracellular ATP stimulated the
      release of [3H]arachidonic acid (AA) and prostaglandin E2 (PGE2) into the medium,
      and enhanced cAMP accumulation in a dose-dependent fashion similar to ATP-induced
      [3H]thymidine incorporation. Inhibitors of the arachidonic acid metabolism
      pathway, quinacrine and indomethacin, partially inhibited the mitogenic effect of
      ATP but not of adenosine. Pertussis toxin inhibited ATP-stimulated DNA synthesis,
      AA release, PGE2 formation, and cAMP accumulation. Down-regulation of protein
      kinase C (PKC) by long-term exposure to phorbol dibutyrate (PDBu) partially
      prevented stimulation of DNA synthesis and activation of the AA pathway by ATP.
      The PKC inhibitor, staurosporine, antagonized mitogenesis stimulated by ATP. No
      synergistic effect was found when PDBu and ATP were added together. Therefore, a
      dual mechanism, including both arachidonic acid metabolism and PKC, is involved
      in ATP-mediated mitogenesis in SMC. In addition, ATP acted synergistically with
      angiotensin II, phospholipase C, serotonin, or carbachol to stimulate DNA
      synthesis. Finally, the possible physiological significance of ATP as a mitogen
      in SMC was further studied. The effect of endothelin and heparin, which are
      released from endothelial cells, on ATP-dependent mitogenesis was investigated.
      Extracellular ATP acted synergistically with endothelin to stimulate a greater
      extent of [3H]thymidine incorporation than was seen with PDGF plus endothelin.
      Heparin, believed to have a regulatory role, partially inhibited the stimulation
      of DNA synthesis caused both by ATP and PDGF.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1358899
TI  - Evaluation of the role of electrostatic residues in human epidermal growth factor
      by site-directed mutagenesis and chemical modification.
AB  - Four residues in the carboxy-terminal domain of human epidermal growth factor
      (hEGF), glutamate 40, glutamine 43, arginine 45, and aspartate 46 were targeted
      for site-directed mutagenesis to evaluate their potential role in epidermal
      growth factor (EGF) receptor-ligand interaction. One or more mutations were
      generated at each of these sites and the altered recombinant hEGF gene products
      were purified and evaluated by radioreceptor competition binding assay. Charge
      conservative replacement of glutamate 40 with aspartate resulted in a decrease in
      receptor binding affinity to 30% relative to wild-type hEGF. On the other hand,
      removal of the electrostatic charge by substitution of glutamate 40 with
      glutamine or alanine resulted in only a slightly greater decrease in receptor
      binding to 25% relative receptor affinity. The introduction of a positive charge
      upon substitution of glutamine 43 with lysine had no effect on receptor binding.
      The substitution of arginine 45 with lysine also showed no effect on receptor
      binding, unlike the absolute requirement observed for the arginine side-chain at
      position 41 [Engler DA, Campion SR, Hauser MR, Cook JS, Niyogi, SK: J Biol Chem
      267:2274-2281, 1992]. Subsequent elimination of the positive charge of lysine 45
      by reaction with potassium cyanate showed that the electrostatic property of the
      residue at this site, as well as that at lysine 28 and lysine 48, was not
      required for receptor-ligand association.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358897
TI  - The alternatively spliced V region contributes to the differential incorporation
      of plasma and cellular fibronectins into fibrin clots.
AB  - During blood clot formation in vivo, plasma fibronectin (pFN) is cross-linked to
      fibrin by coagulation factor XIIIa. Cellular FN (cFN), which localizes to
      connective tissue, is distinguished from pFN by the inclusion of alternatively
      spliced segments. To determine if these two FNs are functionally equivalent in
      blood clotting, the cross-linking of rat pFN and cFN to fibrin was compared in an
      in vitro clotting assay. Fibrinogen and FN were incubated at physiological ratios
      in the presence of thrombin and factor XIIIa. Cross-linking of FN to fibrin was
      monitored by SDS-PAGE and immunoblotting. Over 24 h, cFN was incorporated at a
      significantly slower rate than pFN and was not completely cross-linked to fibrin
      at a temperature that favors this interaction (0 degrees C). This difference was
      observed with purified fibrinogens from human, rat, and bovine and with rat
      plasma and was maintained even after incubation of pFN with rat fibroblasts for
      several days. Using the same assay, purified recombinant V(+)-V0 and V(+)-V+ FN
      dimers resembling pFN and cFN, respectively, showed a similar difference in cross
      linking kinetics. These results suggest that the asymmetric distribution of the V
      region among pFN dimers plays a role in regulating its incorporation into blood
      clots. In fibrin clots, cFN was converted into a set of cross-linked
      intermediates distinct from those of pFN. For example, while pFN was initially
      cross-linked into a pFN-fibrin alpha heterodimer, this product was not a major
      intermediate in clots formed with cFN. This finding, in conjunction with evidence
      for the formation of factor XIIIa-catalyzed cFN-cFN cross-links, indicated that
      cFN molecules interact with each other, and with fibrin, differently from pFN.
      Together, these results show an important functional distinction between pFN and
      cFN.

PMID- 1358900
TI  - Antennapedia homeobox as a signal for the cellular internalization and nuclear
      addressing of a small exogenous peptide.
AB  - In a previous study we demonstrated that a homeobox peptide corresponding to the
      60 amino acid long DNA-binding region of the Drosophila antennapedia homeo
      protein was capable of crossing the plasma membrane of cells in culture. This
      finding has led us to investigate whether chimeric molecules encompassing the
      homeobox would behave in a similar manner. We demonstrate here that a peptide of
      93 amino acids composed of the homeobox and of the C terminus of Rab3, a small
      GTP-binding protein, crosses the membrane of myoblasts, myotubes and neurons and
      is conveyed to their nuclei. This transport is highly efficient, is observed in
      all the cells present in the culture and occurs at 37 degrees C and 12 degrees C
      without quantitative peptide degradation. Beyond its theoretical implications for
      our current views on cellular interactions, this finding could have technical
      repercussions on the development of drugs with intracellular targets.

PMID- 1358901
TI  - Force contribution of the LFA-1/ICAM-1 complex to T cell adhesion.
AB  - Little is known in quantitative terms about forces between cells generated during
      adhesion and recognition, or about the contribution of any one set of molecular
      associations to the development of these forces. To determine the forces involved
      in adhesion dependent on lymphocyte function-associated antigen-1 (LFA-1) and
      intercellular adhesion molecule 1 (ICAM-1), we have measured the junctional
      avidity between single cell pairs consisting of a cloned T cell that expresses
      LFA-1 and a fibroblast cell that expresses MHC class II molecules and ICAM-1
      after transfection. Micromanipulation was used to induce conjugation of cell
      pairs and to determine the force required to separate the conjugate. T cell
      adhesion to three related fibroblast cell lines was compared: the parent line
      that does not express ICAM-1 or other LFA-1 counter-receptors, and two
      transfectants that have high and moderate levels of surface ICAM-1 expression.
      The force needed to separate the conjugates varied with the fibroblast ICAM-1
      expression levels. The T cell adhesion to ICAM-1-expressing fibroblasts was
      strong, and the critical separation stresses measured for the three cell lines
      were 1.4 x 10(3) dyn/cm2 (1 dyn=10(-5) N) for the ICAM-1-negative fibroblast,
      4.98 x 10(3) dyn/cm2 for the fibroblast with a moderate level of ICAM-1
      expression, and 6.25 x 10(3) dyn/cm2 for the fibroblast line with the highest
      ICAM-1 expression. The dependence of adhesion strength on the LFA-1/ICAM-1
      complex was confirmed by the use of blocking antibodies, which showed the
      contribution from the interaction of CD4/MHC class II to be negligible.

PMID- 1358902
TI  - Intranuclear co-location of newly replicated DNA and PCNA by simultaneous
      immunofluorescent labelling and confocal microscopy in MCF-7 cells.
AB  - The intranuclear distribution of newly replicated DNA and of the proliferating
      cell nuclear antigen (PCNA) was mapped by confocal laser scanning microscopy
      after simultaneous immunofluorescent labelling of incorporated bromodeoxyuridine
      (BrdUrd) and PCNA. A mild hydrolysis with HCl followed by an enzymic digestion of
      DNA was used to produce single-stranded DNA required for BrdUrd immunorevelation,
      since this procedure preserves PCNA antigenicity. Optical sections obtained with
      a laser scanning microscope clearly showed a similar distribution of PCNA and
      BrdUrd within the nuclei, thus confirming previous observations on parallel
      labelled synchronized cultures. The intranuclear distribution of PCNA and BrdUrd
      varies concomitantly during the S phase of MCF-7 cells.

PMID- 1358903
TI  - ["In-dartos" orchidopexy in the treatment of cryptorchism].
AB  - Maldescended testis is a common congenital abnormality. The main complications
      are infertility and venue of malignant testicular tumor. If early orchiopexy can
      prevent infertility, it remains a high risk of venue of a malignant tumor. So,
      the best technique of orchiopexy is that which allows and easy clinical follow-up
      of the maldescended testis after surgical treatment, and doesn't involve
      hematoseminal barrear. From the analysis of fourty cases of scrotal pouch
      orchiopexy and a review of the literature, it appears that this procedure is
      efficient and gives more than 90% of good results.

PMID- 1358904
TI  - Sensitive determination of phenothiazines in body fluids by gas chromatography
      with surface ionization detection.
AB  - Fourteen phenothiazine derivatives were tested for their detection by gas
      chromatography (GC) with surface ionization detection (SID). The sensitivity of
      GC-SID was highest with trimeprazine and levomepromazine, which contain aliphatic
      tertiary amino side chains, and lowest with thiethylperazine and thioproperazine,
      which contain sulphur residues. Chlorpromazine, trimeprazine and promazine showed
      excellent linearity between the SID response and the drug amount in the range
      0.25-3.0 pmol on-column. Their detection limits were as low as ca. 5-10 pg (15-30
      fmol) on-column (250-500 pg per ml of body fluid). A detailed procedure for
      isolation of phenothiazines from human whole blood and urine using Sep-Pak C18
      cartridges, before the GC with SID, is also presented. The recoveries of the
      drugs (100 pmol), which were added to 1 ml of whole blood or urine, were more
      than 79%. The baselines remained steady as the column temperature was increased.

PMID- 1358906
TI  - 4th International Symposium on High Performance Capillary Electrophoresis.
      Amsterdam, February 9-13, 1992.

PMID- 1358905
TI  - Selective system of identification and determination of antidepressants and
      neuroleptics in serum or plasma by solid-phase extraction followed by high
      performance liquid chromatography with photodiode-array detection in analytical
      toxicology.
AB  - A selective off-line solid-phase isolation of antidepressants, neuroleptics and
      other structurally related basic drugs from plasma or serum prior to high
      performance liquid chromatography was tested and optimized for general use in
      toxicological analyses where concomitant drugs can be encountered. The sequential
      elution preseparated drug mixtures and simplified the subsequent analytical
      steps. High isolation efficiencies of cyano-bonded silica cartridges from Baker
      for fifteen amine drugs were determined. Isocratic chromatography on
      octadecylsilica proved to be very suitable for broad practical applications in
      complicated cases. The identification of an unknown peak was supported by
      photodiode-array detection in the range 200-400 nm with a resolution of 2 nm. The
      linearity of the assay from therapeutic to toxic concentrations was attained.
      Sufficient sensitivities covering low therapeutic levels of parent drugs and
      their demethylated metabolites were reached. The system is flexible and allows
      various methods of quantitative assay to be devised according to the conditions
      of a particular case in clinical or forensic toxicology.

PMID- 1358907
TI  - Amplification of unknown DNA sequences by sequence-independent nested polymerase
      chain reaction using a standardized adaptor without specific primers.
AB  - A new procedure for sequence-independent PCR amplification of DNA fragments is
      described. DNA from pUC18 plasmid was used as a test DNA. It was digested with a
      frequently cutting restriction enzyme (Sau3A), generating sticky ends. The DNA
      was ligated to a synthetic, non-phosphorylated adaptor and subsequently amplified
      in a nested PCR using two oligonucleotides with sequences derived from the
      adaptor. As little as 1 fg of pUC18 DNA could be detected by this procedure. The
      product was analyzed on a gel and hybridized with a pUC18-specific probe. The
      sequence-independent nested PCR was repeated with different amounts of pUC18 DNA
      in the presence of an excess of non-specific DNA. In these experiments, pUC18 DNA
      fragments were amplified in a concentration-dependent manner. After hybridization
      with a digoxigenin dUTP-labelled pUC18 DNA probe, 1 fg of pUC18 DNA could still
      be detected. This method allows rapid screening of blood for low titred and
      mutated viruses in which primer binding sites are not conserved.

PMID- 1358908
TI  - Antibodies to Puumala virus in humans determined by neutralization test.
AB  - An assay for detection of neutralizing antibodies to Puumala virus using 96-well
      microtiter plates (NT-ELISA) was developed and evaluated. The test proved to have
      similar sensitivity and specificity as an IgG ELISA and indirect
      immunofluorescence test, when screening 187 sera (with an antibody prevalence
      rate of 19%) from normal populations in an endemic area of Nephropathia epidemica
      (NE) in Sweden. NE-patients monitored for 2 years had neutralizing antibodies in
      early sera collected 1-4 days after the onset of disease with a continuous
      increase in neutralizing antibodies with time. Furthermore, high titers of
      neutralizing antibodies were detected 10-20 years post-infection. This
      neutralization assay was also evaluated as a screening method in the production
      of monoclonal antibodies. The format of the NT-ELISA makes it feasible to screen
      a large number of specimens with results similar to the standard plaque or focus
      reduction neutralization tests.

PMID- 1358909
TI  - Clonal origins of adrenocorticotropin-secreting pituitary tissue in Cushing's
      disease.
AB  - It is unclear whether Cushing's disease results from a primary pituitary disorder
      or arises in response to abnormal hypothalamic control of the pituitary gland.
      Clonal analysis can provide information as to whether neoplastic tissue is
      derived from a monoclonal proliferation of a genetically altered cell or from a
      polyclonal expansion of a group of cells affected by a common stimulus. We used X
      linked restriction fragment length polymorphisms at the phosphoglycerate kinase,
      hypoxanthine phosphoribosyltransferase, and DXS255 loci in 11 women with
      biochemically and pathologically confirmed Cushing's disease to determine the
      clonal origins of corticotroph adenomas and corticotroph hyperplasia. Tumor
      tissue from all 10 women with morphologically and immunohistochemically confirmed
      ACTH-secreting pituitary microadenomas demonstrated a monoclonal pattern.
      Pathologically confirmed corticotroph hyperplasia in a patient with a CRH
      secreting bronchial carcinoid was found to be polyclonal. We conclude that
      corticotroph microadenomas in Cushing's disease are monoclonal, supporting the
      theory that a spontaneous somatic mutation is the primary pathogenetic mechanism
      in this disorder. In addition, the demonstration of polyclonality in corticotroph
      hyperplasia implies that excess of hypothalamic hormones is an etiologic
      mechanism in cases of Cushing's syndrome associated with ectopic CRH-secreting
      tumors.

PMID- 1358910
TI  - Chronic somatostatin analog administration in patients with alpha-subunit
      secreting pituitary tumors.
AB  - Glycoprotein hormone-producing (GPH) pituitary adenomas represent approximately
      25% of all pituitary tumors. Elevated serum levels of intact GPHs or their free
      alpha- and beta-subunits have been demonstrated in patients with such tumors, and
      isolated hypersecretion of alpha-subunit has been reported to occur in 7% of
      patients. Somatostatin has been shown to decrease GPH subunit levels in cultured
      adenoma cells in vitro, and somatostatin receptors have been identified on the
      cell membranes of these tumors. We, therefore, investigated the effect of chronic
      somatostatin analog administration on hormone production and tumor size in six
      patients with GPH-producing macroadenomas and elevated serum alpha-subunit
      levels. Patients initially received native somatostatin as an iv 250-micrograms
      bolus at 0800 h, followed by a constant infusion of 2 mg over 4 h, and serum
      alpha-subunit concentrations were measured at 30-min intervals after baseline
      sampling for a total of 9 h. Patients then received a somatostatin analog,
      octreotide (100 micrograms, twice daily, sc) for 8 weeks. Serum alpha-subunit
      levels were determined weekly at 30-min intervals before and for 4 h after the
      0800 h octreotide dose. Pituitary magnetic resonance imaging scans and visual
      field testing were assessed before and after the study. During the 4-h
      somatostatin infusion, four patients had a significant decrease in alpha-subunit
      levels (P < 0.05). During the 8-week chronic octreotide administration period,
      two patients had significant decreases in alpha-subunit levels of 34.6% and 26.7%
      (P = 0.03 and 0.01, respectively). One of these two patients had a small
      reduction in tumor size. Two patients whose serum alpha-subunit level did not
      significantly change while receiving octreotide had a reduction in tumor size or
      definite improvement in visual field abnormalities. Three patients received a
      maximum octreotide dose of 250 micrograms, three times daily. In one patient,
      there was a significant decrease in alpha-subunit levels by 45% (P = 0.0001) in
      association with a marked improvement in visual field abnormalities. In another
      such patient, continued administration of octreotide to a maximum dose of 250
      micrograms, three times daily, was associated with a marked reduction in tumor
      size. Of the four patients who demonstrated significant decreases in alpha
      subunit concentrations during the initial somatostatin infusion, three patients
      had a significant reduction in alpha-subunit levels while receiving octreotide.
      One patient who did not have a decrease in alpha-subunit levels during the
      somatostatin infusion demonstrated a small decrease in tumor size during higher
      dose octreotide treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1358911
TI  - Analysis by the polymerase chain reaction of histocompatibility leucocyte antigen
      DR9-linked susceptibility to insulin-dependent diabetes mellitus.
AB  - DNA sequence analysis of class II HLA from Caucasian and black patients with type
      1 (insulin-dependent) diabetes mellitus has suggested that aspartic acid at
      position 57 (Asp 57) of the DQ beta chain provides protection against insulin
      dependent diabetes mellitus (IDDM). In contrast, most Japanese patients with IDDM
      have Asp 57-positive alleles. To determine the reason for the differences and to
      localize the HLA-linked diabetogenic gene in Japanese, we studied the DQA1 and
      DQB1 genes of Japanese patients with IDDM and control subjects by the polymerase
      chain reaction in combination with restriction fragment length polymorphism
      analysis. Associations of DQA1*0301 and DQB1*0303 with IDDM were observed.
      DQA1*01 was associated negatively with IDDM. The HLA-DR9 haplotype, which is
      associated positively with IDDM in Japanese, was associated with DQA1*0301 and
      DQB1*0303, indicating that the Japanese DR9 haplotype is the same as that in
      caucasians but different from that in blacks. Of the loci on Japanese DR9
      haplotypes, the DQA1*0301 allele showed the highest association with IDDM.
      DQB1*0303 was also positively associated with IDDM. Since DQB1*0303 is identical
      to DQB1*0302 except that it contains Asp 57, the data suggests that an Asp 57
      positive allele confers susceptibility to IDDM when the whole molecule of the DQ
      beta chain is similar to other susceptible DQ beta chains. DQA1*0301 appears to
      be a marker of IDDM in all these populations: Japanese, caucasian, and black.

PMID- 1358914
TI  - Myelin Destruction and Remyelination, Workshop. France, 27-30 November 1991.

PMID- 1358915
TI  - Lymphocyte migration into the CNS modelled in vitro.
AB  - We report on a series of experiments which examines the factors controlling
      lymphocyte adhesion to brain endothelium in vitro and the factors which control
      cell migration across the endothelium, using a new migration assay. Although
      lymphocyte adhesion preceded migration across the brain endothelium, the two
      processes are not identical. We noted that activated CD4+ T cells were
      particularly good at migrating across endothelia. CD8+ T cells and B cells did
      not migrate but adhered well to endothelia. Moreover, the endothelium maintained
      high levels of cell traffic without being disrupted and without exhausting the
      molecular systems which allowed migration. From the viewpoint of migration of
      dividing cells, the state of lymphocyte activation appeared to be the most
      important controlling factor--these cells migrated equally well across
      endothelium activated with cytokines or untreated endothelium. The kinetics of
      adhesion suggested that the LFA-1/ICAM-1 and VLA-4/VCAM combinations of adhesion
      molecules were important in controlling migration. With antibody blocking
      studies, the role of the LFA-1/ICAM-1 system was equivocal. While anti-LFA-1
      blocked lymphocyte adhesion, anti-ICAM-1 did not, suggesting that the level of
      ICAM-1 was not critical.

PMID- 1358913
TI  - Secretory immunoglobulins in serum from human immunodeficiency virus (HIV)
      infected patients.
AB  - Infection by the human immunodeficiency virus is associated with polyclonal B
      cell activation and increased levels of serum IgA. In order to characterize the
      molecular species of serum IgA, we have measured total IgA, IgA1, and IgA2 in
      sera from 60 HIV-1-infected patients and 40 healthy controls. In addition,
      secretory IgA (S-IgA), secretory IgM (S-IgM), free immunoreactive secretory
      component (SC), and the distribution of monomeric and polymeric IgA were
      determined. The data confirm the elevation of total serum IgA levels in HIV-1
      infected patients, and both IgA1 and IgA2 concentrations are elevated.
      Furthermore, the data show a substantial increase in serum levels of both
      monomeric and polymeric IgA. Serum S-IgA levels were significantly increased in
      CDC group II patients versus controls and more frequently elevated in CDC group
      IV patients. The highest S-IgA levels were found among patients with the lowest
      blood CD4+ cell counts. Serum S-IgA levels were not correlated with serum levels
      of either total IgA or polymeric IgA. Serum S-IgM levels were also increased in
      HIV-1-infected patients and positively correlated with serum S-IgA levels.
      Conversely, serum levels of free SC were not altered. An increase in serum S-IgA
      was not related to human hepatitis B virus infection and/or to hepatic
      dysfunction or to diarrhea or overt intestinal infection. The data indicate that
      secretory Ig (S-IgM and S-IgA), which are likely to be produced at mucosal sites,
      increase in the serum of HIV-1-infected patients.

PMID- 1358912
TI  - In vivo models of human lymphopoiesis and autoimmunity in severe combined immune
      deficient mice.
AB  - The discovery of the SCID mouse mutation has been an important advance for the
      study of human lymphopoiesis and autoimmunity. Further work in the SCID mouse
      models described in this review should yield important new information related to
      transplantation of human hematopoietic stem cells across HLA barriers,
      characterization of hematopoietic development in vivo, and identification of
      pathogenic human T cell clones in organ-specific autoimmune diseases. If
      pluripotent hematopoietic stem cells and pathogenic autoimmune T cells can be
      defined using SCID mouse recipients, this would pave the way for development of
      novel strategies for bone marrow transplantation and for interventional
      immunotherapy of autoimmune diseases targeted at the T cell receptor (99).

PMID- 1358916
TI  - Developmental effects of basic fibroblast growth factor and platelet-derived
      growth factor on glial cells in a three-dimensional cell culture system.
AB  - In order to study peptide growth factor action in a three-dimensional cellular
      environment, aggregating cell cultures prepared from 15-day fetal rat
      telencephalon were grown in a chemically defined medium and treated during an
      early developmental stage with either bovine fibroblast growth factor (bFGF) or
      platelet-derived growth factor (PDGF homodimers AA and BB). A single dose (5-50
      ng/ml) of either growth factor given to the cultures on day 3 greatly enhanced
      the developmental increase of the two glia-specific enzyme activities, 2',3'
      cyclic nucleotide 3'-phosphohydrolase (CNP) and glutamine synthetase (GS),
      whereas it had relatively little effect on total protein and DNA content.
      Distinct patterns of dose-dependency were found for CNP and GS stimulation. At
      low concentrations of bFGF (0.5-5 ng/ml) and at all PDGF concentrations applied,
      the oligodendroglial marker enzyme CNP was the most affected. A relatively small
      but significant mitogenic effect was observed after treatment with PDGF,
      particularly at higher concentrations or after repetitive stimulation. The two
      PDGF homodimers AA and BB were similar in their biological effects and potency.
      The present results show that under histotypic conditions both growth factors,
      bFGF and PDGF, promote the maturation rather than the proliferation of immature
      oligodendrocytes and astrocytes.

PMID- 1358917
TI  - Recruitment of CD11b/CD18 to the neutrophil surface and adherence-dependent cell
      locomotion.
AB  - Chemotactic stimulation of neutrophils results in translocation of CD11b/CD18
      (Mac-1) from intracellular storage pools to the cell surface. Though results from
      several laboratories indicate that the newly arrived surface Mac-1 is not
      involved in the adherence induced by the initial stimulus, the present study
      addresses the hypothesis that this Mac-1 plays a role in subsequent adherence
      dependent functions. The response of human neutrophils to changing concentrations
      of a chemotactic stimulus was evaluated by determining the amount of newly
      arrived surface Mac-1, and Mac-1-dependent adhesion and locomotion. Small step
      wise increases in the concentration of f-Met-Leu-Phe (FMLP) resulted in
      proportional stepwise increases in surface Mac-1 that plateaued within 2-4 min.
      This newly arrived Mac-1 supported adhesion to protein-coated surfaces only when
      the cells were exposed to an additional increase in the FMLP stimulus level.
      Adherence-dependent cellular locomotion was evaluated in chambers that allowed
      rapid changes in the stimulus concentration. Repeated small increments in the
      stimulus level at 200-s intervals resulted in significantly longer migration
      paths than a single-step increase in the stimulus. The results support the
      hypothesis that small increments in the chemotactic stimulus bring Mac-1 to the
      cell surface, and this newly mobilized Mac-1 is available for adherence-dependent
      locomotion with subsequent increases in the concentration of the stimulus.

PMID- 1358918
TI  - Pharmacological tolerance to alpha 1-adrenergic receptor antagonism mediated by
      terazosin in humans.
AB  - Chronic administration of alpha 1-receptor antagonists is associated with loss of
      clinical efficacy, especially in congestive heart failure, although the mechanism
      is uncertain. To evaluate changes in venous alpha 1-adrenoceptor responsiveness
      during chronic alpha 1-adrenoceptor blockade, dose-response curves to
      phenylephrine and angiotensin II were constructed in 10 healthy subjects before,
      during, and after administration of terazosin 1 mg orally for 28 d. Terazosin
      initially shifted the dose-response curve of phenylephrine to the right, with a
      significant increase in ED50 for phenylephrine from a control value of 102 to 759
      ng/min on day 1 of terazosin (P < 0.001). However, by day 28, the dose-response
      curve had shifted back towards baseline with an ED50 of 112 ng/min. After
      discontinuing terazosin, the ED50 for phenylephrine remained near the baseline
      value, indicating no evidence of supersensitivity to phenylephrine. There was no
      change in responsiveness to angiotensin II during the course of treatment with
      terazosin. Plasma terazosin concentrations were stable throughout the period of
      drug administration. The mean Kd of terazosin was estimated as 11 +/- 15 nM in
      the first few days of treatment. This study demonstrates that pharmacological
      tolerance to the alpha 1-adrenoceptor blocking action of terazosin occurs in man
      and may be responsible for loss in efficacy with chronic therapy.

PMID- 1358919
TI  - Effects of transforming growth factor-beta on murine astrocyte glutamine
      synthetase activity. Implications in neuronal injury.
AB  - Cytokines have been implicated in the pathogenesis of a number of brain diseases
      in which neurological dysfunction has been attributed to a change in amino acid
      neurotransmitter metabolism. In the present in vitro study, we investigated the
      effects of cytokines on astrocyte glutamine synthetase (GS) activity and
      subsequently on N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity.
      Proinflammatory cytokines IL-1 alpha, IL-1 beta, and IL-6 at a concentration of
      20 ng/ml did not affect GS activity; however, tumor necrosis factor-alpha
      inhibited this activity by 20% in mixed neuronal/astrocyte cultures. Treatment
      for 24 h with transforming growth factor (TGF)-beta 1 or -beta 2 inhibited up to
      60% GS activity. TGF-beta 2 also inhibited GS in enriched astrocyte cultures with
      an ED50 of 10 pg/ml. Antibodies specific to TGF-beta 2 blocked this effect.
      Treatment of astrocytes with TGF-beta 2 (250 pg/ml) resulted in markedly dilated
      rough endoplasmic reticulum. Since astrocyte GS may play a protective role in
      NMDA receptor-mediated neurotoxicity, we treated mixed neuronal/astrocyte
      cultures with TGF-beta 2 (250 pg/ml) and found a threefold potentiation of NMDA
      receptor-mediated neurotoxicity. These data suggest that TGF-beta impairs
      astrocyte GS function and enhances neurotoxicity, thus providing insight into
      understanding one mechanism of cytokine-mediated central nervous system disease.

PMID- 1358920
TI  - Treatment of posttraumatic stress disorder with eye movement desensitization.
AB  - This case report describes the successful treatment of a posttraumatic stress
      disorder (PTSD) using eye movement desensitization (EMD). The client, a 40-year
      old male, presented with an 8-year history of PTSD following an incident in which
      he was shot with a hand gun and left dying. Using EMD treatment, this trauma was
      quickly desensitized. Two earlier traumas with similar themes then emerged and
      they too were desensitized. Test results, taken pre-treatment and posttreatment,
      along with the client's verbatim account of cognitive and behavioral changes 8
      months later, converged to document the successful treatment outcome.

PMID- 1358921
TI  - Clinical and immunological assessment of HIV infection.

PMID- 1358922
TI  - Double-blind placebo-controlled trial of terazosin effect on blood pressure and
      urinary output of dopamine in hypertensive patients.
AB  - In a parallel, double-blind study, 12 untreated hypertensive patients received
      terazosin (2-4 mg/day for 4 weeks), and 12 received placebo during the same
      period. Systolic and diastolic blood pressure decreased significantly in the
      terazosin group, from 150 +/- 5.0 mmHg systolic and 99.6 +/- 2.0 diastolic before
      treatment, to 134.0 +/- 7.0 systolic and 85.6 +/- 3.0 mmHg diastolic at week 4 of
      treatment. No significant blood pressure changes occurred in the placebo group.
      Blood pressure decrease showed a positive correlation (r = .62 and r = .52 for
      systolic and diastolic blood pressure, respectively) with the patient's age (P
      less than .05). Total plasma cholesterol decreased 18% in the terazosin group (P
      less than .05) and 9% in the placebo group (P greater than .05). Urinary dopamine
      excretion decreased significantly from 692.8 +/- 180.0 to 330.5 +/- 52.0
      micrograms/24 hours in the terazosin group (P less than .05) and showed a
      nonsignificant increase in the placebo group. Compared with 22 age- and sex
      matched healthy volunteers, urinary dopamine excretion in the hypertensive group
      before treatment was not statistically different (779.3 +/- 83.1 micrograms/24
      hours). Dopamine excretion was higher in untreated hypertensive men and in male
      healthy volunteers compared with women. The decrease of urinary dopamine
      excretion observed under terazosin treatment could be due to a decrease of kidney
      dopamine synthesis or release induced by blood pressure reduction, or secondarily
      to the blockade of kidney alpha 1-receptors, modulating dopamine excretion. No
      significant changes were observed in urinary excretion of noradrenaline and
      adrenaline.

PMID- 1358923
TI  - The site of gastrointestinal absorption of gepirone in humans.
AB  - This study was conducted in seven healthy male subjects and was performed over
      four sessions with a 1-week washout between sessions. It was designed to compare
      the bioavailability of an oral 20-mg gepirone dose (treatment 1) with that
      obtained after application of the same dose by gastric intubation to the distal
      (treatment 2) and proximal (treatment 3) regions of the small intestine, and
      after 4 consecutive 5-mg gepirone doses given orally at hourly intervals
      (treatment 4). Serial blood samples were taken over 24 hours after dose after
      each treatment. Plasma concentrations of gepirone and 1-(2-pyrimidinyl)
      piperazine (1-PP), a metabolite of gepirone, were quantitated by gas
      chromatography-mass spectrometry. Mean gepirone time to reach peak concentration
      (tmax) after treatments 1, 2, and 3 ranged between 0.57 and 1.07 hours. There
      were no significant differences between sites and treatments for gepirone t1/2,
      which ranged between 2.8 and 3.3 hours. The mean gepirone maximum peak plasma
      concentration (Cmax) was significantly higher (P less than .05) after treatment 2
      (12.92 +/- 7.24 ng/mL) compared with treatment 1 (6.79 +/- 3.54 ng/mL) or
      treatment 3 (6.33 +/- 2.26 ng/mL). Gepirone area under the curve (AUCinf) was
      also significantly higher (P less than .05) after treatment 2 (29.83 +/- 17.42
      ng.h/mL) compared with treatment 1 (18.07 +/- 6.10 ng.h/mL) or treatment 3 (17.74
      +/- 7.69 ng.h/mL). There were no significant differences in gepirone AUCinf
      between treatments 1 and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358924
TI  - Hypothyroidism complicated by angina pectoris: therapeutic approaches.
AB  - The association of hypothyroidism and coronary artery disease is not uncommon.
      The precipitation of angina pectoris, cardiac arrhythmia, and even myocardial
      infarction may occur in patients when initiating rapid replacement therapy for
      hypothyroidism. This is particularly true when replacement therapy is instituted
      in elderly persons or in patients with preexisting coronary artery disease. A
      starting daily dose of 12.5 to 25 micrograms and increments of 25 micrograms
      every 2 to 3 weeks is recommended. Close monitoring of cardiac symptoms is
      essential to avoid side effects. Medical management of angina pectoris includes
      administration of beta-blockers, nitrates, or at times combination antianginal
      therapy may be most effective. Persistence of angina in these patients may
      require coronary angiography with subsequent angioplasty or coronary artery
      bypass surgery.

PMID- 1358925
TI  - Long distance directed axonal growth from human dopaminergic mesencephalic
      neuroblasts implanted along the nigrostriatal pathway in 6-hydroxydopamine
      lesioned adult rats.
AB  - Dissociated ventral mesencephalon of 6 to 8-week-old human embryos were implanted
      by stereotaxic injection at different sites along the nigrostriatal pathway in
      adult rats, previously subjected to a 6-hydroxydopamine lesion of the intrinsic
      mesotelencephalic dopamine pathways. The recipients were immunosuppressed by
      daily injections of cyclosporin A to prevent rejection. At 13-20 weeks after
      transplantation, the implanted human neurons and their associated fiber
      outgrowths were visualized with a species-specific antibody recognizing human,
      but not rat, intermediary neurofilaments (HNF). From implants placed in the host
      rostral mesencephalic region, HNF-positive axonal projections were seen to extend
      in large numbers rostrally along the medial forebrain bundle and the internal
      capsule, and ramify within the caudate putamen, the ventral striatum and the
      amygdaloid nuclei (a distance of about 5-6 mm), and more sparsely in the frontal
      cortex and the olfactory bulb (a distance of about 10 mm). From implants placed
      in the internal capsule, abundant HNF-positive axons extended in the rostral, but
      not caudal, direction along the myelinated fiber bundles into the caudate putamen
      and the ventral striatum. Tyrosine hydroxylase (TH) immunohistochemistry revealed
      that the vast majority of the rostrally projecting HNF-positive axons were also
      TH-positive, and that the graft-derived axons gave rise to dense TH-positive
      terminal networks, above all in large areas of the previously denervated caudate
      putamen. From control implants of cortical neuroblasts, axonal projections were
      seen along the medial forebrain bundle and the internal capsule, but the axons
      were TH-negative and showed only sparse projections to the striatal areas.
      Instead, dense projections were seen, e.g., in the frontal cortex. The results
      demonstrate a remarkable ability of human mesencephalic neuroblasts to extend
      axons along the trajectories of the nigrostriatal and mesolimbocortical pathways
      to reach and innervate the principal striatal and limbic target areas in the
      forebrain. This shows that the basic requirements for the formation of long
      axonal pathways may be present in the adult mammalian central nervous system
      (CNS) at least for certain types of projection neurons. Furthermore, it implies
      that the developing human neuroblasts can escape the inhibitory features known to
      be present along myelinated growth trajectories in the adult mammalian brain. In
      addition, the present approach may offer new possibilities for functional neural
      grafting in the rat Parkinson model, since transplanted nigral neurons placed in
      their natural position within the rostral mesencephalon could provide an
      anatomically and functionally more integrated system than the standard model with
      ectopically placed intrastriatal nigral grafts.

PMID- 1358927
TI  - Beta-adrenergic blocking drugs and psoriasis.

PMID- 1358926
TI  - Pemphigus vulgaris in siblings: HLA-DR4 and HLA-DQw3 and susceptibility to
      pemphigus.
AB  - BACKGROUND: The association of pemphigus vulgaris with the HLA serotypes, DR4 and
      DRw6, and with the DQ-beta chain alleles, DQw1 and DQw3, suggests that there is a
      genetic predisposition to this disease. However, familial cases of pemphigus
      vulgaris are exceedingly rare. OBJECTIVE: We studied two siblings with pemphigus
      vulgaris and three unaffected family members to determine whether an HLA allele
      was associated with the development of pemphigus vulgaris in this family.
      METHODS: We utilized restriction fragment length polymorphism methods using the
      HLA-DR beta 1, HLA-DQ alpha, and HLA-DW beta 1 genes as cDNA probes. RESULTS: We
      found that the affected siblings share the haplotype HLA-DR4 and the DQw.3.2
      allele. CONCLUSION: Our findings of gene sharing among siblings with pemphigus
      vulgaris lend support to previous studies of unrelated Caucasian patients, which
      implicated DQw3 allele polymorphisms in conferring susceptibility to pemphigus.

PMID- 1358928
TI  - Response of aged versus young skin to intradermal administration of interferon
      gamma.
AB  - BACKGROUND: Interferon gamma (IFN-gamma) induces the interaction of intercellular
      adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen type 1
      expression, and of HLA-DR antigens by keratinocytes. OBJECTIVE: The aim of the
      present study was to determine the potential ability of aged versus young skin to
      respond to intradermal administration of IFN-gamma, as an in vivo immunologic
      stimulus. METHODS: For 3 consecutive days elderly and young volunteers were
      injected with 10 micrograms of recombinant IFN-gamma diluted in 0.1 ml of sterile
      water. On day 5, punch biopsy specimens were obtained from the injected sites.
      Histologic and immunohistochemical stainings were performed on all sections.
      RESULTS: ICAM-1 was expressed by keratinocytes in both aged and young skin. An
      impairment was manifested mainly by the reduced accumulation of mononuclear cells
      throughout the dermis, the absence of HLA-DR expression by keratinocytes in 7 of
      10 elderly volunteers, and the absence of an effect on the Langerhans cell
      population. CONCLUSION: This observation shows a diminished immune response in
      aged skin.

PMID- 1358929
TI  - Minocycline hyperpigmentation: model for in situ phagocytic activity of factor
      XIIIa positive dermal dendrocytes.
AB  - Pigmentary disorders resulting from the prolonged use of the semisynthetic
      tetracycline derivative antibiotic, minocycline, are rare but well recognized
      sequelae of ingestion of this drug. We present two cases of women with bullous
      pemphigoid who developed blue-black pigmentation in areas of scarring on the legs
      after oral minocycline therapy. On histologic examination, the deposited pigment
      was localized within dendritic cells limited to the upper dermis.
      Immunohistochemical analysis revealed these cells to be factor XIIIa positive
      dermal dendrocytes which was confirmed by transmission electron microscopy. We
      believe these cases demonstrate, in-situ, the phagocytic capabilities of this
      recently described cell population.

PMID- 1358930
TI  - Repeated administration of antidepressant drugs reduces regional somatostatin
      concentrations in rat brain.
AB  - A possible role for somatostatin in affective disorders is suggested by its low
      concentration in cerebrospinal fluid of patients with depression. Therefore, we
      studied the regional effects of antidepressant drugs and antimanic agents on
      somatostatin concentrations in rat brain. Repeated, but not acute, administration
      of clomipramine, a specific serotonin uptake inhibitor, caused a highly
      significant, widespread reduction in somatostatin levels. Somatostatin content
      was similarly reduced in the hypothalamus, and midbrain and thalamus following
      repeated administration of zimelidine, another specific serotonin uptake
      inhibitor. Repeated administration of either imipramine, maprotiline, mianserin,
      carbamazepine or zotepine were without effect on somatostatin levels. These
      results suggest that somatostatin in the brain might be involved in therapeutic
      effects of some of antidepressant drugs.

PMID- 1358931
TI  - Beta-agonists, airway hyperresponsiveness, and asthma.

PMID- 1358932
TI  - Bronchodilator and bronchoprotective effects of salmeterol in young patients with
      asthma.
AB  - BACKGROUND: In adults with asthma, the selective beta 2-adrenergic agonist
      salmeterol has a prolonged bronchodilator and bronchoprotective effect. To date,
      there are few published studies of salmeterol in children. METHODS: We compared
      the bronchodilator and bronchoprotective effects of salmeterol, 25 and 50
      micrograms, with salbutamol, 200 micrograms, and with placebo, administered via
      metered-dose inhaler, in a randomized, double-blind, within-patient, four-way
      crossover, single-dose study in 20 children. RESULTS: Mean baseline forced
      expiratory volume in 1 second (FEV1) and PC20 methacholine were not significantly
      different (p > 0.05) on the 4 study days, and did not change significantly after
      placebo. FEV1 increased significantly from 5 to 30 minutes after salbutamol, and
      from 5 minutes to 12 hours after 25 micrograms or 50 micrograms salmeterol,
      compared with placebo. After 25 micrograms or 50 micrograms salmeterol, FEV1 was
      significantly lower than after salbutamol at 5 and 10 minutes, did not differ
      from salbutamol at 30 minutes, and was significantly greater than after
      salbutamol from 3 to 12 hours. No significant difference occurred between the
      effect of 25 micrograms salmeterol and the effect of 50 micrograms salmeterol on
      FEV1. After salbutamol, there was a significant increase in PC20 only at 30
      minutes. After 25 micrograms or 50 micrograms salmeterol, PC20 increased
      significantly from 30 minutes to 12 hours. Salmeterol, 25 micrograms and 50
      micrograms provided significantly greater bronchoprotection than salbutamol from
      3 to 12 hours and from 30 minutes to 12 hours, respectively. Salmeterol, 50
      micrograms, provided significantly better bronchoprotection than 25 micrograms
      salmeterol from 30 minutes to 12 hours. The amount of change in PC20 accounted
      for by change in FEV1 varied from 14% to 28%, indicating that protection against
      bronchoconstriction was not entirely dependent on bronchodilation. CONCLUSIONS:
      Salmeterol is a potent, long-acting bronchodilator, with a slower onset of
      bronchodilation than salbutamol. It provides significantly greater and longer
      lasting protection against bronchoconstriction than salbutamol.

PMID- 1358933
TI  - Spinal cord blood flow decreases following chemical stimulation of the rostral
      ventrolateral medullary pressor area in anesthetized rats.
AB  - In urethane-anesthetized, paralyzed and artificially ventilated rats, the neurons
      in the rostral ventrolateral medullary pressore area (VLPA) were chemically
      stimulated by microinjections of L-glutamate (1.7-5.0 nmol in 100 nl of 0.9%
      sodium chloride solution) and the spinal cord blood flow (SCBF) was determined
      using a combination of labeled microspheres (57Co, 113Sn and 46Sc). In order to
      measure SCBF at normotension, moderate hypotension within the lower limit of
      spinal cord autoregulation was induced by controlled hemorrhage (n = 12).
      Unilateral chemical stimulation of the VLPA in these rats increased arterial
      blood pressure (ABP) but it remained within normotensive range. The SCBFs of
      cervical, thoracic and lumbar cord decreased significantly from 27 +/- 3 (mean +/
      S.E.M.) to 20 +/- 2 (P less than 0.01), from 22 +/- 1 to 17 +/- 2 (P less than
      0.05), and from 41 +/- 5 to 26 +/- 3 (P less than 0.05) ml.min-1.(100 g)-1,
      respectively. The spinal cord vascular resistances (SCVRs) of cervical, thoracic
      and lumbar cord increased significantly from 3.7 +/- 0.4 to 5.0 +/- 0.6 (P less
      than 0.05), from 4.2 +/- 0.2 to 5.9 +/- 0.7 (P less than 0.05), and from 2.5 +/-
      0.2 to 3.8 +/- 0.4 (P less than 0.05) mmHg per [ml.min-1.(100 g)-1],
      respectively. During the chemical stimulation of the VLPA, SCBF increased in
      response to the changes in arterial PaCO2 indicating that the reactivity of
      spinal cord vasculature was intact (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358934
TI  - Effect of nucleus tractus solitarius lesions on cardiovascular responses elicited
      from the caudal ventrolateral medulla.
AB  - Neurons in the caudal ventrolateral medulla (CVLM) which inhibit sympathetic
      vasomotor tone may have reciprocal connections with the nucleus tractus
      solitarius (nTS). This study determined whether changes in arterial pressure
      elicited by chemical excitation or inhibition of neurons in the vasodepressor
      region of the rabbit CVLM depend on the integrity of the nTS. Unilateral
      injections of L-glutamate (10 pmol to 100 nmol), or bilateral injections of GABA
      (1 nmol to 125 nmol), were made into the CVLM, and dose-response effects on
      arterial pressure determined. The nTS was then bilaterally cauterized, or
      inhibited by local injections of muscimol, and the dose-response curves were
      repeated. Neither cauterization nor injection of muscimol significantly altered
      the slope of the log dose-response curves for L-glutamate, but nTS muscimol
      increased the fall in arterial pressure for each dose of L-glutamate (P less than
      0.01). Cauterization of the nTS significantly (P less than 0.01) increased the
      slope of the curve relating dose of GABA to rise in arterial pressure observed,
      after injection of GABA into the CVLM. This increase in slope was similar to the
      increase observed when GABA is injected into the CVLM in baroreceptor-denervated
      rabbits. We conclude that neither the depressor nor the pressor response evoked
      by stimulation or inhibition of the CVLM is dependent on the integrity of the
      nTS. Inactivation of the nTS tends to increase the magnitude of the CVLM
      responses, possibly by removal of baroreceptor-mediated buffering of the
      responses.

PMID- 1358936
TI  - Longitudinal study of psychotropic drug use by elderly nursing home residents.
AB  - In this longitudinal study of patterns of use of psychotropic drugs by a cohort
      of elderly nursing home residents (N = 5,752), drug use was examined upon
      admission, 3 months later, and at discharge/end of study. At each time point, 17%
      of the cohort used neuroleptics. Half of the subjects discontinued neuroleptics
      at each time point; however, a similar number were initiated on the drug.
      Benzodiazepines were used by 21%, 15%, and 15% at each of the three time points,
      respectively. Twice as many people were taken off benzodiazepines as initiated on
      them following admission. The 5% rate of antidepressant use was constant across
      the three time periods, although only half of those who took antidepressants upon
      admission were also taking them upon discharge/end of study. The amount of change
      due to discontinuation of these drugs and adjustment in dosage levels challenges
      the stereotype of the "neglected psychotropic drug user" in nursing homes.

PMID- 1358935
TI  - Generalized thyroid hormone resistance: identification of an arginine to cystine
      mutation in codon 315 of the c-erb A beta thyroid hormone receptor.
AB  - The present report studies a large kindred (WR) with generalized thyroid hormone
      resistance that has varying degrees of neuropsychological dysfunction,
      hyperactivity, poor attention span, decreased IQ and/or abnormalities in spatial
      perception. In this kindred, there has been found tight linkage of the syndrome
      with the c-erb A beta gene. The present study was performed to identify the
      presence of a possible gene mutation as a cause for this syndrome. DNA from
      peripheral leukocytes was isolated from 15 unaffected and 8 affected individuals
      from the kindred. Primers encompassing exons 9 (nucleotides 1171-1429) and 10
      (nucleotides 1430-1698) were synthesized and used in PCR reactions to amplify
      these exons. Direct sequencing revealed a consistent substitution in each
      affected subject, but in none of the unaffected individuals, of a C to T change
      in one allele from nucleotide 1243, resulting in an arg to cys change in codon
      315. The mutant and wild-type human beta 1 receptors were prepared and their
      translated proteins were analyzed for T3 binding. The WR T3 receptor from
      affected patients had reduced T3 binding affinity, with values approximately 2.5
      x 10(10) M-1 compared to about 5 x 10(10) M-1 in normals. In summary, we have: i)
      identified a consistent and reproducible mutation of a C to T change in
      nucleotide 1243 in each of the affected but in none of the unaffected individuals
      of a large well characterized kindred with generalized thyroid hormone
      resistance; and ii) noted that the WR allele causes an approximate 50% decrease
      in the T3 binding affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1358937
TI  - Breast Cancer Screening in Older Women. Forum. Sturbridge, Massachusetts, July 30
      August 2, 1990.

PMID- 1358938
TI  - Abstracts of the 3rd International Conference Current Trends in Chronically
      Evolving Viral Hepatitis. Pisa, Italy, 4-7 October 1992.

PMID- 1358939
TI  - Selective Serotonin Reuptake Inhibitors in Psychiatric Practice. Proceedings of a
      symposium. Copenhagen, Denmark, March 22, 1991.

PMID- 1358940
TI  - Selective Serotonin Uptake Inhibitors in Depression and Other Indications.
      Symposium proceedings. Florence, Italy, 11 June 1991.

PMID- 1358941
TI  - Self- and other-directed human aggression: the role of the central serotonergic
      system.

PMID- 1358942
TI  - Application of an optimized immunostaining technique to evaluate the
      heterogeneous secretory response from porcine somatotropes by cell blotting.
AB  - The objective of the present study was to quantify the absolute hormone release
      from individual porcine pituitary cells incubated on polyvinylidene difluoride
      (PVDF) transfer membranes (cell-blot assay). After immunoperoxidase staining,
      growth hormone (GH) release from isolated somatotrope cells appeared like a
      colored zone of secretion surrounding the cell. Optical densities of these
      secretion zones were quantitated by computerized image analysis and translated
      into picograms by means of an appropriate standard curve. As a prior step, the
      staining method and the optimal immunocytochemical conditions were selected by
      applying purified porcine growth hormone (pGH) to the transfer membranes. The
      avidin-biotin-peroxidase nickel-intensified (ABC-Ni) method produced a better
      resolution than the peroxide-anti-peroxidase (PAP) method, although both
      techniques were similar with regard to background, sensitivity, and range of
      quantitation. The amount of GH released from single porcine somatotropes was
      highly heterogeneous, although the cells were treated under the same conditions.
      Moreover, this fact was consistent with the stimulation of the average release of
      GH by GH-releasing factor (GHRF) but not by GHRF+somatostatin (SRIF). Our results
      confirm the availability of the recently developed cell-blot assay and support
      the concept of functional heterogeneity in anterior pituitary cell populations.

PMID- 1358943
TI  - Antibiotic resistance associated with selective decontamination of the digestive
      tract.
AB  - Selective decontamination of the digestive tract (SDD) appears to reduce
      infection, particularly pneumonia, in intensive care, and some patients benefit
      markedly. Gram-positive overgrowth and antibiotic resistance in both Gram
      positive and Gram-negative organisms has been recorded. However, the clinical and
      epidemiological significance of these observations is still debated. Future
      studies will need to be of sufficient size and duration to provide good quality
      data on which the safety and efficacy of SDD can be properly judged.

PMID- 1358944
TI  - Clinically significant coagulase-negative staphylococci: identification and
      resistance patterns.
AB  - Coagulase-negative staphylococci (CNS) of clinical significance, isolated from
      131 patients, were investigated during the period 1989-90 in northern Norway. The
      staphylococci were isolated from blood cultures (68; 51.9%), vascular catheters
      (6), osteomyelitis foci (13), postoperative and other wounds (15), and urine
      samples (29). The use of Gram-positive Identification Card (Vitek) and 'Staph
      zym' (Rosco) both gave a primarily correct species identification in 95% of the
      cases. Staphylococcus epidermidis was the predominant species (72.3%).
      Methicillin-resistance was found in 40 of 131 (30.5%) of all CNS and in 34 of 96
      (35.4%) of S. epidermidis. Methicillin-resistant (MR) S. epidermidis strains were
      usually resistant to gentamicin, tetracycline, chloramphenicol and trimethoprim.
      MR strains were, however, less resistant to sulphonamides than methicillin
      sensitive strains (10 out of 34 vs. 55 out of 62). Methicillin-resistance implied
      resistance to all beta-lactam antibiotics, including imipenem. Among S.
      epidermidis, MR isolates increased from 10% in 1987 to 35.4% in 1989-90. All
      strains were sensitive to vancomycin and rifampicin.

PMID- 1358945
TI  - Plasmid-pattern analysis in the differentiation of Staphylococcus epidermidis
      isolates.
AB  - Plasmids carried by 29 Staphylococcus epidermidis isolates from two different
      origins (invasive and carrier, non-hospital-associated strains) were analysed by
      agarose gel electrophoresis in order to evaluate any association with virulence.
      Plasmid patterns were found to be characteristic of individual strains and no
      particular molecular size band was found to correlate with either of the two
      categories of isolates. It is concluded that the plasmid pattern analysis carried
      out could not differentiate between carrier and invasive S. epidermidis, but did
      provide a useful tool for epidemiological investigation.

PMID- 1358946
TI  - The relative importance of the routes and sources of wound contamination during
      general surgery. II. Airborne.
AB  - The influence of airborne bacteria on wound contamination during biliary surgery
      was studied. When bacteria grew in the bile they accounted for most of the
      bacteria in the wound but when the wounds were free of bile bacteria many of the
      bacteria came from the patient's skin. It was only in wounds with little
      contamination from non-airborne routes that it was possible to demonstrate an
      effect of airborne contamination. In such a situation it was estimated that a
      reduction in the airborne bacteria in the operating room of about 13-fold would
      reduce the wound contamination by about 50%. The contamination of patient drapes
      from various sources and its relationship to wound contamination was studied. It
      was demonstrated that in areas away from the wound, the bacterial concentration
      on the drape surface was significantly affected only by airborne bacteria. In the
      area close to the wound, airborne bacteria and bacteria from the wound
      significantly affected drape contamination. However, it was found that more
      bacteria transferred from the wound to the drape surface than vice versa.
      Punctured gloves, impervious gowns and the number of bacteria on the patient's
      skin did not significantly affect the counts on the drapes' surfaces.

PMID- 1358947
TI  - Colonization of burns and the duration of hospital stay of severely burned
      patients.
AB  - In a retrospective study the influence of several factors on the length of
      hospital stay of severely burned patients (at least 24% total body surface area)
      has been investigated. The influence of these factors was studied by means of the
      Cox model survival analysis with time-varying covariates. Seventy-one patients
      were included in this study. The mean age was 32 years (range 1-82 years), the
      mean total body surface area burned 40% (range 24-80%) and the mean full
      thickness area burned 32% (range 10-70%). The length of hospital stay was
      positively correlated with the extent of the burned area and with the age of the
      patient. Wound colonization with Enterobacteriaceae or with a combination of
      Pseudomonas spp. and Staphylococcus aureus was also associated with a prolonged
      stay in hospital.

PMID- 1358948
TI  - An outbreak of Candida tropicalis peritonitis in patients on intermittent
      peritoneal dialysis.
AB  - An outbreak of Candida tropicalis peritonitis in intermittent peritoneal dialysis
      patients during a 6-week period is reported from a general hospital. Five
      patients were involved and there were three deaths. The strains recovered from
      affected patients were identical to those recovered from the water baths on the
      basis of biotyping, antimicrobial susceptibility pattern and chromosomal DNA
      fingerprints. No further cases were identified on subsequent surveillance after
      the prohibition of wet-warming of peritoneal dialysate in the hospital.

PMID- 1358949
TI  - A novel electrical method for the prevention of microbial colonization of
      intravascular cannulae.
AB  - An electrical device designed to prevent microbial attachment to plastic
      intravascular cannulae is described. The device produced an electrical current
      (10 microA) in both carbon-impregnated and 'Hydrocath' cannulae. In-vitro models
      were utilized to demonstrate that the current can block several mechanisms by
      which microorganisms gain initial access to intravascular devices, including
      extra- and intra-luminal routes. The electrical system prevented organisms from
      traversing along both the external and internal surfaces of the cannulae.
      Effective prevention of cannula colonization was demonstrated subsequent to
      challenge with Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus
      faecalis, Proteus mirabilis, Pseudomonas aeruginosa and Candida albicans. The
      findings suggest that the electrical device may offer in-vivo cannula protection
      from microbial attachment and colonization, thereby reducing the potential for
      infection.

PMID- 1358950
TI  - Costs of an outbreak of wound infections in an orthopaedic ward.
AB  - An outbreak of serious wound infections occurring in an orthopaedic ward is
      reported. The outbreak involved 10 patients, all of whom had undergone clean,
      orthopaedic operative procedures. The outbreak was eventually terminated by
      discarding five damaged and contaminated mattresses. The costs incurred during
      this outbreak were calculated using a retrospective comparative study. The
      infected patients had an average increased hospital stay of 17 days and average
      increased costs of 2220 pounds. The outbreak demonstrated the high costs of
      hospital-acquired infection and the need for further investment in infection
      control programmes.

PMID- 1358951
TI  - Vascular catheter-related sepsis: diagnosis and prevention.

PMID- 1358952
TI  - A new approach to the management of Broviac catheter infection.
AB  - Infection continues to be a major complication of the use of indwelling venous
      catheters. In an attempt to avoid removal of the catheter and to minimize the
      systemic side-effects of antibiotics, the potential value of in-situ treatment of
      confirmed Broviac catheter infection was assessed in carefully selected patients
      attending an oncology unit. Fourteen episodes from 11 children were included in
      the study. A variety of organisms were encountered. Infective episodes were
      divided into two categories: (a) those occurring in patients with negative
      peripheral blood cultures and neutrophil count greater than 1.5 x 10(9) l-1 which
      were treated only by local instillation of heparinized antibiotic 8-hourly for 7
      14 days (N = 8); (b) those occurring simultaneously with positive peripheral
      blood culture (or peripheral blood culture not performed) regardless of
      neutrophil count, or infection restricted to Broviac catheter but with a
      neutrophil count of less than 1.5 x 10(9) l-1; these were treated, with one
      exception, as above with the addition of systemic antibiotics (N = 6). Treatment
      was successful in 100% of infective episodes with negative cultures achieved
      between 5 and 12 days. Catheters remained in use a mean of 118 days following
      treatment of infection. This approach has obvious advantages but requires careful
      patient selection and monitoring. It prolongs the catheter life, obviates the
      need for systemic antibiotics for a local infection, and with appropriate
      instruction to parents and family practitioner, treatment may be administered on
      an outpatient basis.

PMID- 1358953
TI  - Virulence factors in Escherichia coli from urinary tract infections in patients
      with spinal injuries.
AB  - A collection of 70 strains of Escherichia coli from urinary tract infections in
      spine-injured patients undergoing long-term bladder catheterization were tested
      for characteristics that have been associated with the ability to produce
      pyelonephritis. The incidence of the virulence factors were: mannose-resistant
      haemagglutinins (30%), P-fimbriae (17%), haemolysin (27%), K-antigens (28%) and
      aerobactin (by bioassay 33%, by gene probe 39%). Only 54% of the strains belonged
      to the O-serotypes usually associated with urinary tract infections. E. coli
      carrying the full complement of virulence factors were rare in the urinary tract
      of the spinal patients and were not associated with episodes of symptomatic
      pyelonephritis. It is clear that the neuropathic bladder and the presence of the
      catheter permits a wide variety of bacterial types to colonize the urinary tract
      and cause infection of the kidney. The identification of host markers rather than
      bacterial factors is suggested as a more fruitful approach to the early detection
      of cases likely to progress to pyelonephritis in this group of patients.

PMID- 1358954
TI  - Antibiotic resistance of urinary pathogens isolated from patients attending the
      Toronto Hospital between 1986 and 1990.
AB  - A study was carried out on 1523 urinary isolates obtained at The Toronto
      Hospital, Canada's largest tertiary care establishment, over three 1-month
      periods in 1986, 1987 and 1990. Escherichia coli was the most frequently isolated
      organism, with Enterococcus spp. the second most common isolate in 1986 and 1987,
      and Streptococcus spp. in 1990. Pseudomonas aeruginosa isolates were found to be
      resistant to many of the antimicrobial agents tested. Resistance patterns were
      found to commonly prescribed ampicillin, co-trimoxazole and, to some extent, the
      new fluoroquinolones, ciprofloxacin and norfloxacin. These results are relevant
      to the treatment and management of urinary tract infections in patients attending
      a tertiary care hospital.

PMID- 1358955
TI  - A study of glutaraldehyde disinfection of fibreoptic bronchoscopes experimentally
      contaminated with Mycobacterium tuberculosis.
AB  - Mycobacteria are difficult to inactivate, and concern about the spread of
      tuberculosis at bronchoscopy has a major influence on infection control
      practices. Recommendations from the UK Department of Health are based largely on
      in-vitro mycobactericidal assays which do not take into account the particular
      conditions encountered in endoscopy units. In this applied study cleaning and
      disinfection methods were examined using five bronchoscopes that were heavily
      contaminated with a recent isolate of Mycobacterium tuberculosis in sputum.
      Cleaning reduced contamination by a mean 3.5 log(10) colony forming units (cfu)
      per ml; all bronchoscopes were free of detectable mycobacteria after 10 min in 2%
      alkaline glutaraldehyde (AG). It is recommended that all bronchoscopes be
      thoroughly pre-cleaned and disinfected in 2% AG for 20 min as part of a uniform
      policy of infection control.

PMID- 1358956
TI  - An examination of needlestick injury rates, hepatitis B vaccination uptake and
      instruction on 'sharps' technique among medical students.
AB  - A 12-question survey designed to examine venepuncture techniques and instruction
      and uptake of hepatitis B vaccination was completed by 172 of the 275 medical
      students to whom it was distributed (a response rate of 62.5%). Seventy-five
      injuries were reported, at an average of 0.3 per student per year. Of the
      respondents, 63% resheathed needles after use, a practice frequently cited as a
      cause of needlestick injury. However, in this sample resheathing was not
      significantly associated with a higher or lower injury rate (chi 2 = 2.07, P >
      0.1). Of the respondents from the most recent intake, only 20 out of 57 had
      completed a course of hepatitis B vaccinations prior to the commencement of
      venepuncture duties. There was almost universal ignorance concerning the correct
      course of action following 'sharps' injury. Recommendations are made concerning
      hepatitis B vaccination and teaching strategies for medical students.

PMID- 1358957
TI  - An evaluation of the Hamo LS-76 washing, drying and disinfecting machine for
      anaesthetic equipment.
AB  - This report evaluates a machine designed to wash, disinfect and dry anaesthetic
      equipment. Following adjustments to the program these objectives could be
      reliably achieved within a reasonable time. Multifunction machines should be
      considered for future use in Sterile Service Departments, although a careful
      assessment of the workload capacity should be made before purchase.

PMID- 1358958
TI  - Biochemical mis-identification of Brucella melitensis and subsequent laboratory
      acquired infections.
AB  - Brucella species are mis-identified in the API 20NE system as Moraxella
      phenylpyruvica (profile number 1200004). Since some Brucella spp. grow readily in
      routine blood culture medium and may be isolated from patients without clinically
      obvious brucellosis, the risk of laboratory-acquired brucellosis exists. We
      describe two such cases.

PMID- 1358959
TI  - Diversity of klebsiellae with extended-spectrum beta-lactamases at a Turkish
      university hospital.

PMID- 1358960
TI  - A hospital outbreak of scabies.

PMID- 1358961
TI  - Outbreak of chest infections with Serratia marcescens.

PMID- 1358963
TI  - Emergence of resistance during selective digestive decontamination?

PMID- 1358962
TI  - An outbreak of EMRSA 2 associated with long-term colonization of medical staff.

PMID- 1358964
TI  - Clostridium difficile infection: responses, relapses and re-infections.
AB  - Clostridium difficile infection is a common and potentially lethal complication
      of antibiotic usage. Since the aetiology of antibiotic-associated colitis was
      discovered 14 years ago, two antibiotics in particular, metronidazole and
      vancomycin, have been used to treat C. difficile infection. Studies comparing the
      efficacy of these antibiotics are reviewed. It is now apparent that many of the
      so-called 'relapses' of C. difficile infection following antibiotic treatment
      are, in fact, re-infections. Such findings have major infection control
      implications.

PMID- 1358965
TI  - In-vitro efficacy of a central venous catheter ('Hydrocath') loaded with
      teicoplanin to prevent bacterial colonization.
AB  - A technique is described by which a central venous catheter ('Hydrocath') is
      loaded with the glycopeptide teicoplanin for the prevention of catheter
      infection. Catheters are immersed in teicoplanin solution and, due to the
      hydrophilic surface coating of the 'Hydrocath' catheter, teicoplanin is absorbed
      by the surface layer. The catheter loading is influenced by the experimental
      conditions and is assessed by measuring teicoplanin elution from the catheter
      using a bioassay. Increasing the antibiotic concentration, incubation time and
      temperature leads to the binding of higher amounts of teicoplanin to the
      catheter, resulting in a higher teicoplanin release from the catheter.
      Experiments on in-vitro bacterial adherence to teicoplanin-loaded and unloaded
      catheters reveal that the initial bacterial adhesion is not prevented. However,
      in the case of the teicoplanin-loaded catheter initially adherent bacteria are
      eliminated from the catheter surface, thus preventing catheter colonization by
      bacteria for at least 48 h. Such loaded catheters could be suitable for
      inhibiting early-onset, catheter-related infections.

PMID- 1358966
TI  - Analysis of CD4+ T cells that provide contact-dependent bystander help to B
      cells.
AB  - Although cognate, MHC-restricted interaction of Th cells with Ag-presenting B
      cells provides effective help to a resting B cell, substantial B cell responses
      have also been seen with preactivated T cell clones that cannot recognize Ag on
      the B cell but apparently interact in a noncognate fashion (the bystander
      response). Here, we have investigated the ability of distinct Th cell subsets and
      T cells activated by different stimuli to support such bystander B cell
      responses. We have also determined which cytokines are involved. We generated
      distinct CD4+ T cell subsets specific for both alloantigen (using normal mice)
      and cytochrome c (using TCR transgenic mice). To compare cognate and bystander
      help, we analyzed the response of allogeneic (cognate) vs syngeneic (bystander)
      resting B cells in the former case, and the response of syngeneic B cells in the
      presence vs absence of Ag, in the latter case. Both approaches gave similar
      results. T cells stimulated with Ag for 24 h (naive and memory cells) or
      generated from naive cells over 4 days in the presence of exogenous IL-2 ("Th1
      like" effectors) induced B cells to secrete minimal amounts of bystander Ig (20
      to 700 ng/ml), less than 6% of the Ig induced under cognate conditions. In
      contrast, effectors generated in IL-4 or IL-6 ("Th2-like" and "Th0-like") induced
      significantly more bystander Ig (4 to 9 micrograms/ml), which was 18 to 30% of
      the amount produced during a cognate response. Restimulation of Th cell
      populations with anti-CD3, instead of Ag/APC, enhanced their ability to induce
      bystander Ig to levels 40 to 100% of those produced through cognate interaction.
      The addition of anti-cytokine Ab to bystander responses indicated that the
      cytokines utilized were similar to those mediating response after cognate
      interaction. Addition of exogenous cytokines did not specifically enhance the
      extent of the bystander response as a function of the cognate response. These
      results suggest that most Th cells can efficiently activate only those B cells
      that present relevant Ag on class II MHC, but that highly
      activated/differentiated Th effectors also have the ability to induce significant
      bystander B cell responses through noncognate interactions. We also conclude that
      the mode of Th cell activation and the cytokines encountered during Th
      differentiation play a major role in the capacity of helper cells to initiate a
      bystander response.

PMID- 1358967
TI  - CD27, a member of the nerve growth factor receptor family, is preferentially
      expressed on CD45RA+ CD4 T cell clones and involved in distinct immunoregulatory
      functions.
AB  - CD27 is a disulfide-linked 120-kDa homodimer expressed on the majority of
      peripheral T cells at variable density that belongs to the recently defined nerve
      growth factor receptor family. mAb reactive with CD27 can either enhance or
      inhibit T cell activation, suggesting a crucial role in the process of T cell
      activation. We now show that CD27 is preferentially expressed on the
      CD45RA+CD45RO-CD29low subset of CD4 cells. CD27 expression on this subset is
      maintained for a prolonged period in culture after PHA activation. In contrast,
      CD45RA-CD45RO(+)-CD29high subset of CD4 cells express very low level of CD27, and
      its expression is lost within 2 wk after PHA activation. To further analyze the
      differential expression of CD27 on these reciprocal subsets of CD4 cells, we
      developed T cell clones by stimulating isolated CD4+CD45RA+ and CD4+CD45RO+
      populations with PHA. T cell clones derived from cells originally CD45RA+
      retained both CD45RA and CD27 expression, whereas T cell clones derived from
      cells originally CD45RO+ were CD45RA- and CD27-. In functional assays, IL-4
      production could only be induced in CD45RA-CD27- CD4 clones by stimulation with
      PMA and ionomycin. Four of six CD45RA+ CD4 clones had suppressor activity in PWM
      driven IgG synthesis, whereas five of six CD45RA- CD4 clones had helper activity.
      Of interest, the suppressor activity of CD45RA+CD27+ clones was partially blocked
      by pretreatment with anti-CD27 mAb (1A4). Anti-1A4 pretreatment of these T cell
      clones resulted in elevation of intracellular cAMP levels. Thus, CD27 appears to
      play a role in the function of CD45RA+CD27+ CD4 cells, and may be involved in
      suppressor activity of these cells at least in part via its effects on cAMP
      production.

PMID- 1358968
TI  - Enhanced lymphokine production and lymphokine receptor expression in multiple
      antibody-stimulated human CD4+ peripheral blood lymphocytes.
AB  - Treatment of T lymphocytes with antibodies directed against the T cell receptor
      CD3 complex results in cellular activation that can be augmented by costimulation
      through other cell surface receptors. The activities of anti-CD3-stimulated human
      CD4+ PBL were compared to anti-CD3 plus anti-CD2-, anti-CD4-, or anti-CD11a (LFA
      1)-stimulated cells. [3H]thymidine incorporation, lymphokine receptor expression,
      expansion of cell numbers, and lymphokine mRNA and protein were measured. Forty
      eight hours after activation, costimulated CD4+ cells demonstrated increased
      numbers of cells positive for surface IL-2R alpha-chain, IL-2R beta-chain, IFN
      gamma receptors, and TNF-alpha receptors. By day 6, costimulated cells exhibited
      a sevenfold greater expansion in cell numbers compared to cells stimulated with
      anti-CD3 alone. Anti-CD3 plus anti-CD11a stimulation consistently induced the
      highest secretion of IL-2 and IFN-gamma, whereas variation in secretion of TNF
      alpha and IL-4 between different donors was noted. Analysis of lymphokine
      receptor mRNA demonstrated increased levels of mRNA for IL-2R alpha-chain and IFN
      gamma receptor that preceded the phenotypic changes on the cell surface. In
      contrast, levels of IL-2R beta-chain and the TNF-alpha receptor mRNA decreased
      after stimulation. Amounts of IL-2, IL-4, and TNF-alpha, but not IFN-gamma,
      secreted also correlated with the levels of mRNA measured in the cells. Although
      costimulation through CD2, CD4, or LFA-1 appeared equally effective for the
      induction of the lymphokine receptors, these additional stimuli had a different
      impact on lymphokine secretion. These results indicate that specific control of
      lymphokine secretion and receptor induction can be another function of the CD2,
      CD4, and CD11a cell surface receptors. This control is evident at both
      transcriptional and post-transcriptional levels.

PMID- 1358969
TI  - Intercellular adhesion molecule-1 (ICAM-1)-dependent and ICAM-1-independent
      adhesive interactions between polymorphonuclear leukocytes and human airway
      epithelial cells infected with parainfluenza virus type 2.
AB  - Acute respiratory virus infections are often associated with an early influx of
      neutrophils (PMN) into the airways. Maximal cytoxic injury by PMN depends on
      tight cell-cell adhesion. Infection of some cell types by respiratory and other
      viruses has been shown to increase PMN adhesion to these cells by undefined
      mechanisms. We studied adhesion by human PMN to monolayers of primary (1 degree)
      human tracheal epithelial cells (TEC) or an immortalized cell line derived from
      human TEC, 9HTEo-, that had been infected with parainfluenza virus type 2 (PiV2).
      PMN adhesion to uninfected 1 degree TEC was very low (< 5%), but PMN adhesion to
      PiV2-infected 1 degree TEC was greatly increased (89 +/- 7%). PMN adhesion to
      9HTEo- cells was 47 +/- 6%, but increased, 87 +/- 8%, for PiV2-infected 9HTEo-
      cells. Surface intercellular adhesion molecule-1 (ICAM-1) expression on 1 degree
      TEC, as determined by immunofluorescence flow cytometry, was relatively low (23
      fluorescence units) but doubled by 24 h after PiV2 infection and tripled by 48 h.
      The 9HTEo- cells constitutively expressed higher levels of surface ICAM-1 (120
      units) which did not increase with PiV2 infection. Treatment of non-PiV2-infected
      9HTEo- cells with mAb (R6.5) to ICAM-1 reduced PMN adhesion to these cells from
      47 +/- 8 to 23 +/- 5%. Identical mAb treatment of either 1 degree TEC or 9HTEo-
      cells infected with PiV2 had no significant effect on PMN adhesion. Treatment of
      the PMN with mAb against CD11a, CD11b, or CD18 markedly reduced PMN adhesion to
      PiV2-infected 1 degree TEC and 9HTEo- cells. We conclude that PiV2 infection of
      human TEC causes a marked increase in their adhesive interactions with PMN by
      inducing increased surface expression of both ICAM-1 and one or more, as yet
      uncharacterized, non-ICAM-1 adhesion molecules that function as counter-receptors
      for CD11/CD18 on PMN. These mechanisms of adhesion may play a role in epithelial
      damage during acute respiratory virus infections.

PMID- 1358970
TI  - Inhibition of lymphocyte endothelial adhesion and in vivo lymphocyte migration to
      cutaneous inflammation by TA-3, a new monoclonal antibody to rat LFA-1.
AB  - Lymphocyte function-associated Ag-1 (LFA-1) or CD11a/CD18 mediates lymphocyte
      adhesion to cultured vascular endothelial cells (EC). Thus, LFA-1 likely plays a
      major role in lymphocyte migration out of the blood, but there is little
      information on this in vivo. Small peritoneal exudate lymphocytes (sPEL) and
      lymph node (LN) lymphoblasts adhere to cytokine-activated EC and preferentially
      migrate to cutaneous inflammatory sites. The role of LFA-1 in the adherence and
      in vivo migration of these T cells was determined. Because of a lack of anti-rat
      LFA-1, mAb were prepared to rat T cells. One mAb, TA-3, inhibited homotypic
      aggregation; T cell proliferation to Ag, alloantigens, and mitogens; stained all
      leukocytes; and immunoprecipitated 170- and 95-kDa polypeptides from lymphocytes
      and neutrophils. TA-3 binding to lymphocytes also required Ca2+, but not Mg2+.
      Thus, TA-3 appears to react with rat LFA-1. TA-3 inhibited spleen T cell adhesion
      to unstimulated EC by 30% and to IFN-gamma, TNF-alpha, IL-1 alpha, and LPS
      stimulated EC by 50 to 60% but inhibited sPEL EC adhesion by only 10%. TA-3 also
      strongly inhibited anti-CD3-stimulated LN T cell adherence. The migration of
      spleen T cells to delayed-type hypersensitivity and skin sites injected with LPS,
      poly I:C, IFN-gamma, IFN-alpha/beta, and TNF was inhibited by 72 to 88% by TA-3,
      and was decreased by 50% to peripheral LN. TA-3 caused less but still 50 to 60%
      inhibition of sPEL migration to inflamed skin. Lymphoblast migration to skin was
      inhibited 40 to 80% and to PLN by 30%. Migration of lymphocytes from all sources
      to mesenteric LN was inhibited by 32 to 60%. In conclusion, LFA-1 mediates much
      of the adherence of spleen T cells and lymphoblasts to EC in vitro, most of the
      migration of these cells to dermal inflammation and about 50% of the homing of LN
      and spleen T cells to peripheral and mesenteric LN. sPEL are less dependent on
      LFA-1 for adhesion to EC in vitro and for migration to inflamed skin and LN in
      vivo.

PMID- 1358971
TI  - IL-4 synthesis by in vivo primed keyhole limpet hemocyanin-specific CD4+ T cells.
      I. Influence of antigen concentration and antigen-presenting cell type.
AB  - The development of IL-4 synthesis is a critical step in the regulation of immune
      responses. Our studies focused on the production of IL-4 by CD4+ T cells taken
      from mice primed with the Ag keyhole limpet hemocyanin (KLH). In vitro
      stimulation of such CD4+ T cells with KLH resulted in little or no IL-4
      production in the first 24 h of stimulation, indicating that little IL-4
      synthesis persists in vivo after immunization. However, IL-4 was generated later
      at 24 to 96 h of in vitro stimulation, indicating that the potential to produce
      IL-4 was retained by the KLH-primed CD4+ T cells, but that in vitro maturation of
      the T cells was required before initiation of IL-4 production. The amount of IL-4
      produced in vitro by KLH-primed T cells from BALB/c mice was influenced by
      several factors. First, stimulation of KLH-primed CD4+ T cells with higher in
      vitro concentrations of KLH resulted in more IL-4 synthesis, but this was
      accompanied by more IFN-gamma as well. Second, primed CD4+ T cells from lymph
      nodes (axillary and popliteal) produced significantly more IL-4 than primed
      splenic T cells. Third, when primed B cells were utilized to present low
      concentrations of KLH to the T cells, IL-4 but not IFN-gamma was produced. In
      contrast, use of splenic adherent cells resulted in IFN-gamma but not IL-4
      synthesis. These restricted patterns of lymphokine synthesis, however, were
      observed only with low concentrations of KLH. Fourth, the amount of IL-4 produced
      and its regulation by the presence of IFN-gamma differed among mouse strains, in
      that BALB/c T cells produced much more IL-4 than H-2 identical DBA/2 T cells. Our
      results characterizing the APC and Ag dose requirements for IL-4 synthesis in KLH
      primed T cells from different strains of mice are consistent with previous
      observations that distinct strains of mice differ in the type of immune response
      generated against different pathogens, and with the concept that low Ag
      concentrations preferentially result in high levels of IgE synthesis, which is
      absolutely dependent on IL-4 production.

PMID- 1358972
TI  - Natural killer (NK) cell stimulatory factor or IL-12 has differential effects on
      the proliferation of TCR-alpha beta+, TCR-gamma delta+ T lymphocytes, and NK
      cells.
AB  - We have analyzed the effects of NK cell stimulatory factor/IL-12, on
      proliferation of PBL and their subsets. IL-12 synergizes with lectins and phorbol
      diesters to induce proliferation of CD4+ and CD8+ peripheral blood T lymphocytes.
      In the case of phorbol-diester-induced proliferation, the effect of IL-12 is in
      part mediated by induced IL-2 production, as suggested by the observation that IL
      12 enhances IL-2 production in these cultures and that anti-IL-2 antibodies
      inhibit proliferation. IL-12 synergizes also with anti-CD3 antibodies and with
      allogeneic stimulation in MLC in inducing T cell proliferation. IL-12 alone is
      mitogenic for preactivated T and NK lymphoblasts. This mitogenic effect is
      observed with similar doses of IL-12 on NK lymphoblasts as well as on CD4+ and
      CD8+ TCR-alpha beta+ and on TCR-gamma delta+ lymphoblasts. On TCR-alpha beta+ T
      lymphocytes the effect of IL-12 is always additive to that of IL-2 over a wide
      dose range. The same effect is observed on highly activated, actively
      proliferating NK cells. However, on NK and TCR-gamma delta+ lymphoblasts
      reverting to a resting state after stimulation and on a TCR-gamma delta+ acute
      leukemia-derived T cell line, IL-12 inhibits significantly the proliferation
      induced by moderate to high doses (10 to 100 U/ml) of IL-2. This inhibitory
      effect is, at least in part, indirect, and depends on IL-12-induced production of
      TNF. Neutralizing anti-TNF antibodies, but not anti-IFN-gamma and anti
      transforming growth factor antibodies, restore by more than 70% the inhibition of
      proliferation induced by IL-12 in these cultures. However, TNF alone cannot mimic
      the inhibitory effect of IL-12 on the IL-2-induced proliferation of NK and TCR
      gamma delta+ lymphoblasts, suggesting the involvement of additional mechanisms.
      The relevance of these findings for the biology of lymphocyte subsets mediating
      MHC nonrestricted cytotoxicity is discussed.

PMID- 1358973
TI  - Granuloma T lymphocytes in murine schistosomiasis mansoni have somatostatin
      receptors and respond to somatostatin with decreased IFN-gamma secretion.
AB  - The granulomas of mice infected with Schistosoma mansoni for 8 wk have
      macrophages that secrete somatostatin 1-14 (SOM). Within the granuloma, SOM has
      no known function. To uncover the possible significance of SOM produced within
      this granulomatous inflammation, we sought SOM receptors on distinct cellular
      components of the granuloma to identify cells targeted for SOM action. [125I]SOM
      1-14 bound to dispersed granuloma inflammatory cells specifically and reversibly.
      Scatchard analysis suggested one receptor type (kDa 4.28 x 10(-9) M). Octreotide,
      a stable SOM derivative, displaced radioligand (kDa 1.01 x 10(-10) M), but SOM 1
      28, substance P, and vasoactive intestinal peptide did not. The SOM receptor
      localized exclusively to a subset of granuloma CD4+ T lymphocytes. Using IL-5 and
      IFN-gamma ELISA, it was shown that granuloma T cells can secrete appreciable IL-5
      and IFN-gamma when stimulated with Ag or mitogen. Both SOM and octreotide at
      concentrations as low as 10(-10) M substantially decreased IFN-gamma secretion
      from Ag or mitogen-stimulated T cells, but at concentrations as high as 10(-6)
      did not affect IL-5 production. Octreotide administered to animals in vivo
      decreased the intensity of the granulomatous response. Thus, some granuloma T
      cells have SOM 1-14 receptors. SOM 1-14, a product of granuloma macrophages, may
      participate in regulation of the granulomatous response by modulating the
      secretion of some lymphokines. Octreotide, a clinically useful SOM analog, mimics
      the action of SOM on the immune system.

PMID- 1358974
TI  - Role of neutrophils and CD4+ T lymphocytes in the primary and memory response to
      nonimmunogenic murine mammary adenocarcinoma made immunogenic by IL-2 gene.
AB  - TS/A is a spontaneous adenocarcinoma, apparently not immunogenic in BALB/cnAnCr
      mice. TS/A cells are unable to stimulate a syngeneic antitumor response either in
      vitro or in vivo. To evaluate the immunogenic potential of IL-2-releasing
      neoplastic cells, we used an expression vector to introduce the cDNA coding for
      murine IL-2 into TS/A cells. Six clones releasing between 30 and 6800 U of IL
      2/10(5) cells/ml/48 h have been isolated. Both low (30 U, B1.30) and high (6000
      U, B4.6000) IL-2-releasing clone are capable of stimulating a proliferative and
      cytotoxic response in syngeneic cultures. While the B1.30 clone grows in 60% of
      syngeneic mice with a delayed pattern, the five clones that release higher levels
      of IL-2 are promptly rejected. Rejection is associated with neutrophil
      infiltration, the intensity of which is directly proportional to the amount of IL
      2 released. NK cells and CD4+ lymphocytes are uninfluential, whereas CD8+
      lymphocytes play only a minor role. This neutrophil-dominated rejection leaves a
      long-lasting, tumor-specific, T lymphocyte-mediated immune memory. For its
      induction, CD4+ lymphocytes are required. Their specific activation appears to
      depend on both the amount of IL-2 released and the granulocyte-mediated reaction
      that may lead to a more efficient presentation of tumor-associated Ag. These data
      support the notion that, after transduction of IL-2 gene, cancer cells may elicit
      an immune antitumor response, and stress the potential use of IL-2 as a component
      of new tumor vaccines.

PMID- 1358975
TI  - Comparison of airway and blood eosinophil function after in vivo antigen
      challenge.
AB  - Eosinophils (EOS) are important effector cells in allergic diseases and asthma.
      However, functional characteristics of the EOS have been derived primarily from
      studies of blood cells, and it is unlikely that such assessments reflect events
      occurring in tissues or airways. To establish more precisely the function of
      airway EOS, segmental Ag challenge was used to elicit and isolate large numbers
      of these cells. Airway, as well as blood, EOS were isolated from allergic
      patients 48 h after segmental Ag challenge. Both blood and bronchoalveolar lavage
      (BAL) EOS were fractionated over Percoll density gradients; by using this
      protocol, three density-distinct populations of pure (>90%) EOS were obtained
      from BAL fluid (1.100, 1.095, and 1.090 g/ml) and one from blood (1.100 g/ml).
      The functions of these various populations were compared by measuring superoxide
      generation, adherence to collagen and endothelial cell monolayers, cell surface
      receptors, and in vitro survival. BAL EOS of all three densities had greater
      superoxide generation and adherence with FMLP activation than did corresponding
      blood EOS. In contrast, blood and airway EOS responded similarly to PMA. BAL EOS
      also had increased expression of CD11b/CD18 and HLA-DR. The intracellular calcium
      concentration ([Ca2+]i) was measured with the fluorescent marker indo
      1/acetoxymethyl ester. FMLP caused a greater and more sustained increase in
      [Ca2+]i with BAL than blood EOS. EGTA blocked the sustained component of the
      [Ca2+]i response to FMLP. Our findings indicate that BAL EOS have an enhanced
      [Ca2+]i response to activation that may contribute to their functional up
      regulation.

PMID- 1358977
TI  - 3rd International Langerhans Cell Workshop. Dallas, Texas, December 5-6, 1991.

PMID- 1358978
TI  - Third International Workshop on Langerhans cells: discussion overview.

PMID- 1358976
TI  - Eradication of hantavirus infection among laboratory rats by application of
      caesarian section and a foster mother technique.
AB  - Hantavirus antibodies were demonstrated by the indirect immunofluorescent
      antibody assay, in the serum of inbred strains of laboratory rats, during the
      period 1973-1982, at the Unit of Experimental Immunology in the Catholic
      University of Louvain, Brussels, Belgium. LOU rats, as well as immunocytomas,
      which were requested by laboratories in the U.K. and The Netherlands, were
      supplied at a time when the infection was unknown and unsuspected in Europe.
      Hantavirus-infected laboratory rats were rendered free of virus through re
      derivation by caesarian section and suckling by virus-free foster mothers.
      Immunocytomas were tested for the presence of hantaviruses by implantation into
      seronegative laboratory rats. The strain of hantavirus causing the laboratory
      infection was clearly different from the one circulating in free-living bankvoles
      in Belgium. The exchange of laboratory rats and rat tumours in relation to the
      potential risk of laboratory-acquired hantavirus infection, is discussed.

PMID- 1358980
TI  - Human epidermal keratinocyte expression of sialyl-Lewis X.
AB  - Cell-surface oligosaccharides can function as ligands for intercellular adhesion
      receptors, matrix proteins, and growth factors. We report that human neonatal and
      adult epidermal keratinocytes (KC) express sialyl Lewis X [s-Le(x); SA alpha 2
      3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3R], a ligand for endothelial and
      platelet selectins. Freshly isolated or cultured KC bind FH6 monoclonal antibody
      (MoAb), which is specific for s-Le(x)-containing oligosaccharides. The relevant
      epitope is bona fide s-Le(x), because sialidase treatment of KC suspensions
      abrogates FH6 binding while generating de novo KC reactivity with anti-Le(x). KC
      stained in ice-cold suspension display a knobby membrane distribution of s-Le(x)
      detectable by immunofluorescence microscopy. As others have reported, FH6
      appeared not to bind KC in perpendicular skin sections. However, basal KC in
      intact epidermal sheets exhibited obvious "honeycomb" reactivity with FH6 when
      stained and viewed en face, suggesting that s-Le(x) in intact epidermis may occur
      in bands that parallel the major tissue axis. FH6 specifically immunoprecipitated
      proteins of Mr 34 kd, 44 kd, and 56 kd from [35S]-labeled KC, and anti-Le(x)
      precipitated similar proteins from sialidase-treated KC. The enzymatic basis for
      KC s-Le(x) expression was studied by analyzing acceptor specificities and other
      properties of KC fucosyltransferases. Results indicate that KC express both Lewis
      and myeloid-type alpha 1-3fucosyltransferases. KC s-Le(x) could be an important
      element of the epithelial milieu, because both epithelial cells and immune cells
      that home to epithelia express s-Le(x) and related structures, and because KC s
      Le(x) is well positioned for selectin-mediated platelet binding after trans
      cutaneous wounding. The apparent distributions of s-Le(x) in epidermis and on
      isolated KC are compatible with a functional role for s-Le(x) in these
      intercellular interactions.

PMID- 1358979
TI  - Genetic linkage between the collagen VII (COL7A1) gene and the autosomal dominant
      form of dystrophic epidermolysis bullosa in two Dutch kindreds.
AB  - Epidermolysis bullosa is a heterogeneous group of heritable blistering skin
      diseases affecting epidermis and the dermal-epidermal junction zone. Recently,
      genetic linkage to the type VII collagen gene (Z = 8.77; theta = 0.00) localized
      on chromosome 3p21 was shown in three Finnish families with the autosomal
      dominant form of dystrophic epidermolysis bullosa. Two Dutch kindreds with
      intrafamilial characteristics of both the Cockayne-Touraine type and Bart's
      syndrome of autosomal dominant dystrophic epidermolysis bullosa have been
      studied. Two-point linkage analysis in these two families with the COL7A1 marker
      revealed a combined lod score of Z = 6.08 at theta = 0.00. These data strongly
      suggest that the type VII collagen gene is the candidate gene in these Dutch
      pedigrees. At least two (Cockayne-Touraine and Bart) of the three subtypes of
      dominant dystrophic epidermolysis bullosa seem to represent different forms of
      expression of the same gene defect.

PMID- 1358981
TI  - Co-stimulatory functions of antigen-presenting cells.
AB  - Antigen-presenting cells, in addition to presenting processed antigen, provide co
      stimulatory signals that are necessary for stimulating maximal lymphokine
      production by CD4+ T cells. For interleukin 2 (IL-2)-producing CD4+ T cells, the
      B7 molecule provides an important co-stimulatory signal through interaction with
      its ligand on the T-cell surface, CD28. Populations of antigen-presenting cells
      that express high levels of B7 (e.g., dendritic cells) are much more potent
      stimulators of T-cell activation than cells that fail to express B7 (e.g.,
      resting B cells). An increase in B7 expression could therefore explain the
      increased accessory function gained by Langerhans cells as they leave the skin
      and migrate to the draining lymph node.

PMID- 1358982
TI  - Doses of ultraviolet radiation that modulate accessory cell activity and ICAM-1
      expression are ultimately cytotoxic for murine epidermal Langerhans cells.
AB  - Mechanisms that underlie immunomodulatory properties of ultraviolet (UV)
      radiation remain incompletely characterized. Recently, we have studied effects of
      UV on the functional activity of epidermal Langerhans cells (LC) and have
      attempted to relate inhibitory effects of UV on LC function to modulatory effects
      of UV on adhesion molecule expression by LC. Exposure of LC in vitro to amounts
      of UVB, UVC, or psoralen+UVA (PUVA) radiation that inhibited LC function also
      prevented increased expression of intercellular adhesion molecule-1 by LC in
      vitro. Subsequent studies revealed that amounts of UV radiation that inhibited LC
      function and modulated ICAM-1 expression also decreased LC survival in vitro,
      although UV-induced LC cytotoxicity did not become apparent until 48-72 h after
      UV exposure. Our results are consistent with those of previous studies that
      suggested that low doses of UV radiation were cytotoxic for LC in situ. The
      potential cytotoxicity of UV radiation for LC should be considered when studies
      of effects of UV radiation on immune responses in skin are interpreted.

PMID- 1358983
TI  - Regulation of the skin immune system by retinoids during carcinogenesis.
AB  - One of the immunosuppressive effects of both ultraviolet (UV) light and chemical
      carcinogens is to deplete Langerhans cells (LC) from the epidermis, suggesting
      that these cells play an important role in inducing immune responses to
      developing tumors during the early phases of carcinogenesis. Retinoids such as
      all-trans-retinoic acid (RA) are natural or synthetic derivatives of vitamin A;
      RA binds to nuclear receptors in the skin, effecting transcription of a wide
      range of genes. Topical application of RA prevents the tumor promotor 12-O
      tetradecanoylphorbol-13-acetate (TPA) from depleting the density of LC in murine
      epidermis. In contrast, topical RA did not itself alter the normal LC density. RA
      also inhibited the development of TPA-induced immunosuppression to a locally
      applied contact sensitizer. Topical RA also prevented UV light from reducing the
      density of both LC and Thy-1+ dendritic epidermal cells (Thy-1+ dEC). However,
      the RA treatment did not prevent local immunosuppression to the contact
      sensitizer from developing in response to UV irradiation. The reasons for this
      are unclear, however, it is possible that RA does not inhibit some other
      immunosuppressive effect of UV light. Temarotene, a recently developed synthetic
      retinoid also inhibited UV light from reducing the LC and Thy-1+ dEC density from
      murine epidermis. Thus part of the anti-carcinogenic activity of retinoids may be
      due to their ability to protect LC during the early stages of carcinogenesis.

PMID- 1358984
TI  - Epidermal compromise in American cutaneous leishmaniasis.
AB  - In American cutaneous leishmaniasis (ACL), Leishmania parasites enter the
      epidermis of the host via the bite of infected sandflies. Immune responses
      against the parasite vary from "effective" in localized (LCL) to a state of
      "selective anergy" in diffuse (DCL) cutaneous leishmaniasis, whereas the
      intermediate muco-cutaneous form (MCL) is characterized by an exacerbated cell
      mediated immunity. We have shown that in LCL epidermis, Langerhans cells (LC) are
      increased, HLA-DR is universally expressed and intercellular adhesion molecule-1
      (ICAM-1) immunoreactivity is distributed in patches. In addition, mRNA for IL-1
      beta, IL-8, TNF alpha, TNF beta, and INF gamma may be detected in epidermal
      sheets by reverse transcriptase followed by polymerase chain reaction (RT-PCR).
      In contrast, DCL epidermis shows fewer LC than LCL epidermis, and expression of
      ICAM-1, HLA-DR, and IL-1 beta mRNA cannot be detected. MCL lesions show a mucosal
      epithelium lacking LC, but ICAM-1 is universally expressed. The clinical
      manifestations of ACL can be reproduced experimentally in different strains of
      inbred mice. In healthy mice, we have shown a positive correlation between LC and
      dendritic epidermal T cells (DETC) numbers. This correlation was not, however,
      observed in L. mexicana-infected mice, suggesting that infection alters the
      balance between the two cell types. In addition, agents that modulate LC and DETC
      cell densities change the development of experimental leishmaniasis. These
      results suggest that the epidermis is essential in determining the type of immune
      response that is developed against the Leishmania parasites.

PMID- 1358985
TI  - Association of antibody to human immunodeficiency virus type 1 core protein
      (p24), CD4+ lymphocyte number, and AIDS-free time.
AB  - Serum antibody to p24 (anti-p24) and p24 antigen, alone and in combination with
      CD4+ lymphocyte number, were evaluated as predictors of progression of human
      immunodeficiency virus type 1 (HIV-1) infection. Two hundred six HIV-1-prevalent
      seropositive men in the Multi-center AIDS Cohort Study since 1984-1985 were
      studied cross-sectionally and 84 seroconverters were evaluated longitudinally.
      Cross-sectional analyses revealed significant associations among titer of anti
      p24, CD4+ cell count, disease status (Centers for Disease Control class), and
      progression to AIDS. A high titer of anti-p24 was associated with lack of p24
      antigenemia. Longitudinal studies of seroconverters demonstrated that a low titer
      of anti-p24, low CD4+ cell count, and detection of HIV-1 p24 antigen are
      individually strong predictors of AIDS, but only low CD4+ cell count retains its
      independent predictive value in multivariate analysis of the three markers during
      the period immediately after infection with HIV-1.

PMID- 1358986
TI  - Incidence and natural history of cytomegalovirus disease in patients with
      advanced human immunodeficiency virus disease treated with zidovudine. The
      Zidovudine Epidemiology Study Group.
AB  - Data were analyzed from a multicenter observational cohort study of 1002 persons
      with AIDS or AIDS-related complex (ARC) and total CD4 cell count < 0.25 x 10(9)/L
      treated with zidovudine between April 1987 and April 1988. Cytomegalovirus (CMV)
      disease developed in 109 patients (10.9%), with a 2-year actuarial risk of 15%.
      Manifestations included retinitis (93 patients), esophagitis (10), colitis (8),
      gastritis (1), hepatitis (1), and encephalitis (1). The probability of CMV
      disease at 2 years for patients with initial counts < 0.1 x 10(9)/L was 21.4%,
      compared with 10.3% for patients with initial counts > or = 0.1 x 10(9)/L (P <
      .001). By proportional hazards analysis, baseline CD4 cell count < 0.1 x 10(9)/L,
      enrollment diagnosis of AIDS, and homosexuality were significantly associated
      with subsequently developing CMV disease. Median survival after diagnosis of CMV
      disease was 173 days, and CMV was an independent predictor of death. CMV
      contributes to AIDS-related morbidity and mortality. As new anti-CMV drugs become
      available, prophylaxis should be targeted at individuals with CD4 cell counts <
      0.1 x 10(9)/L.

PMID- 1358987
TI  - Localized, aggregative, and diffuse adherence to HeLa cells, plastic, and human
      small intestines by Escherichia coli isolated from patients with diarrhea.
AB  - Adherence of diarrhea-associated Escherichia coli was studied by scanning
      electron microscopy. Enteropathogenic E. coli (EPEC) adherence factor-positive
      (EAF+) E. coli of EPEC serotypes (class I EPEC) adhered to plastic and human
      jejunal and ileal mucosa, similar to case and HeLa cells. Localized adherence,
      elongation of cell microvilli, and "locking" of the bacterial aggregates by the
      elongated microvilli were evident after incubation for 20 min. EAF+ E. coli
      adhered strikingly to mucus but rarely to M cells in Peyer's patch-associated
      epithelium. Most enteroaggregative E. coli (EAggEC) strains adhered to plastic,
      similar to HeLa cells. Some diffuse-adhering E. coli (DAEC) strains displayed no
      adherence to plastic but formed "dimples" on HeLa cells. Both EAggEC and DAEC
      adhered at lower levels to human small intestines (except M cells) than did EAF+
      E. coli. In all cases of EAF+ E. coli, EAggEC, and DAEC, strains were found with
      atypical characteristics. The data demonstrate the unique adherence
      characteristics of EAF+ E. coli, EAggEC, and DAEC.

PMID- 1358988
TI  - Course of primary candidiasis in T cell-depleted mice infected with attenuated
      variant cells.
AB  - Anti-CD4, anti-CD8, or anti-interferon-gamma (IFN-gamma) antibodies or
      combinations of them were administered in the early stages of chronic infection
      of mice with a Candida albicans live vaccine strain, and the animals were
      monitored for course of primary infection, development of delayed-type
      hypersensitivity, resistance to reinfection, production of interleukin 2 (IL-2)
      and IFN-gamma in vitro by splenic lymphocytes, and levels of IL-2 and IFN-gamma
      transcripts in these cells. CD4+ cell and IFN-gamma depletion resulted in the
      development of fatal candidiasis by the attenuated yeast vaccine. In contrast,
      either treatment alone modified the course but not the outcome of primary
      infection, though each prevented the development of resistance to reinfection.
      Our data thus indicate that both IFN-gamma and CD4+ cells participate in
      resistance to primary infection with attenuated yeast cells and are critical in
      the induction of persistent systemic anticandidal immunity.

PMID- 1358989
TI  - Construction and expression of an enzymatically active human-mouse chimeric
      double-stranded RNA-dependent protein kinase.
AB  - The interferon (IFN)-inducible double-stranded (ds) RNA-activated protein kinase
      (p68 kinase) is a physiologically important enzyme that regulates the rate of
      cellular and viral protein synthesis by phosphorylating and thereby inactivating
      the peptide chain initiation factor 2. We have generated a partial cDNA clone,
      which probably represents the murine p68 kinase, by reverse transcription
      polymerase chain reaction (RT-PCR) using sequence information of the human p68
      kinase. The 725-bp cDNA clone encoded the carboxyl-terminal 238 amino acid
      residues of the mouse kinase. It has 67% overall identity with the corresponding
      region of the human kinase. All the protein kinase catalytic domains are
      conserved in the mouse protein. Moreover, there are additional stretches of
      residues that are totally conserved between the two proteins. The functional
      equivalence of the two proteins was tested by constructing a chimeric cDNA that
      encoded a protein whose amino-terminal 364 residues were of human origin and
      carboxyl-terminal 187 residues were of mouse origin. The chimeric protein was as
      efficient as the human p68 kinase in binding to the dsRNA, autophosphorylating
      and phosphorylating exogenous substrate.

PMID- 1358990
TI  - New Developments in the Biology and Clinical Application of Carcinoembryonic
      Antigen. Seminar. Milan, 28-29 November 1991.

PMID- 1358991
TI  - [Cerebral amyloid angiopathy].

PMID- 1358992
TI  - Macrophage cytoskeleton association with CR3 and CR4 regulates receptor mobility
      and phagocytosis of iC3b-opsonized erythrocytes.
AB  - Alveolar macrophages (AM phi) were examined for CR1 (C3b receptor, CD35), CR3
      (iC3b receptor; CD11b/CD18), and CR4 (iC3b receptor; CD11c/CD18) by assays for
      binding of C3-opsonized sheep erythrocytes (EC3b or EC3bi) and uptake of specific
      monoclonal antibodies (mAbs). In AM phi isolates from nine normal volunteers, 49%
      of cells bound EC3b and 71% bound EC3bi. Quantitation of receptors per cell with
      [125I]mAbs showed 8.5 x 10(4) CR4, 5.1 x 10(4) CR3, and 2.6 x 10(4) CR1. With
      most AM phi preparations, CR3 was the major receptor mediating attachment of
      EC3bi, despite the predominance of CR4 antigens. Anti-CR3 inhibited EC3bi
      rosettes by > or = 50%, whereas anti-CR4 blocked rosettes by < or = 18%. U937
      cells differentiated with phorbol myristate acetate resembled AM phi in receptor
      expression but exhibited almost no CR4-dependent rosetting. Despite the relative
      inability of CR4 to mediate EC3bi attachment, AM phi ingestion of [51Cr]EC3bi was
      blocked by either anti-CR3 or anti-CR4. Two lines of evidence indicated that CR3
      were more mobile within the membrane than were CR4. Immunofluorescence staining
      demonstrated patching and occasional capping of CR3, whereas CR4 remained
      uniformly distributed. This patching and capping of CR3 required the actin
      cytoskeleton, as it was inhibited by cytochalasin D. Modulation experiments using
      surfaces coated with anti-CR3 or anti-CR4 also showed that CR3 was more mobile
      than was CR4. However, there was some variation among AM phi isolates from
      different donors. In seven isolates, no CR4 modulation was produced with anti
      CR4, whereas in six other isolates, CR4 was modulated by 66%. Incubation of cells
      in cytochalasin D increased modulation of both CR3 and CR4 on mAb-coated
      surfaces. Cells exhibiting increased mobility of CR4 showed an increased ability
      to form CR4-dependent EC3bi rosettes. The data are consistent with the hypothesis
      that CR3 and CR4 exhibit a variable association with the cytoskeleton that
      regulates their mobility and function. A relatively mobile subset of CR3 and/or
      CR4 mediates EC3bi attachment, whereas a relatively immobile subset of CR3 and/or
      CR4 fails to mediate EC3bi attachment but functions to promote ingestion of
      EC3bi.

PMID- 1358993
TI  - Role of CD4+ T lymphocytes and interleukin-5 in antigen-induced eosinophil
      recruitment into the site of cutaneous late-phase reaction in mice.
AB  - Previous studies suggested that the eosinophil recruitment into the site of
      cutaneous late-phase reaction (LPR) was dependent on IgE antibody and mast cells.
      In this study, we determined the role of CD4+ T cells and CD8+ T cells in causing
      antigen-induced eosinophil recruitment of LPR in mouse skin. Eosinophil
      infiltration into the subcutaneous tissue of ovalbumin (OVA)-sensitized BALB/c
      mice was biphasic, reaching the first peak at 6 h after the subcutaneous
      challenge with OVA and the second peak at 24 to 48 h. The in vivo depletion of
      CD4+ T cells by pretreatment with anti-L3T4 monoclonal antibody (mAb)
      significantly decreased the second peak (at 24 h and 48 h), but not the first
      peak (at 6 h), of OVA-induced eosinophil infiltration into the skin of OVA
      sensitized mice. However, the depletion of CD8+ T cells by pretreatment with anti
      Lyt-2 mAb had no significant effect on either the first peak or second peak of
      OVA-induced cutaneous eosinophilia. Pretreatment with anti-murine interleukin-5
      (IL-5) mAb also decreased the second peak, but not the first peak, of OVA-induced
      cutaneous eosinophilia. In contrast to the inhibitory effects of depletion of
      CD4+ T cells and of anti-IL-5 mAb on the second peak of antigen-induced cutaneous
      eosinophilia, disodium cromoglycate and a selective antagonist for platelet
      activating factor (PAF) CV-6209 decreased the first peak of OVA-induced cutaneous
      eosinophilia in the mouse. These results indicate that CD4+ T cells, but not CD8+
      T cells, cause the second peak of antigen-induced eosinophil recruitment of
      cutaneous LPR and that IL-5 mediates this eosinophil recruitment. In contrast,
      the first peak of antigen-induced eosinophil recruitment of cutaneous LPR is
      mediated by mast cells and PAF.

PMID- 1358994
TI  - A rapid and reliable method for direct genotyping of codon 360 in the human
      apolipoprotein A-IV gene.
AB  - Human apolipoprotein A-IV exhibits a polymorphism, first investigated at the
      protein level, that is caused by a single amino acid substitution of glutamine to
      histidine at codon 360. Detection of this polymorphism requires polymerase chain
      reaction (PCR) and direct sequencing of the amplified products, radiolabeled
      allele-specific oligonucleotides (ASOs) technique, or restriction enzyme analysis
      of the amplified products. However, these techniques involve the use of
      radioactivity and/or are not well suited to the rapid processing of a large
      number of samples. In this paper, we propose a new technique, a bispecific-allele
      primer amplification, in which a simple electrophoresis of PCR products is used
      for typing the variation at codon 360. The 3' primer of PCR hybridizes with one
      or other homologous sequence in the apoA-IV gene, depending on the presence or
      the absence of the mutation. This differential hybridization of the primer is
      used for typing the variation. In order to demonstrate the validity of this
      system, 120 individuals phenotyped by two-dimensional electrophoresis and
      genotyped by ASO were analyzed by this new technique. The results obtained by the
      latter method are in agreement with those found by the other techniques. However,
      this method is simple, more reliable, and will facilitate population studies
      without using radioactive materials.

PMID- 1358995
TI  - Detection of three separate DNA polymorphisms in the human lipoprotein lipase
      gene by gene amplification and restriction endonuclease digestion.
AB  - A rapid detection method was developed for DNA polymorphisms in the human
      lipoprotein lipase (LPL) gene. The examined polymorphisms include an A-C
      transversion in the 5'-region of intron 3, a T-G transversion that occurs within
      a Hind III site of intron 8, and the previously described C-T transition that
      causes a Pvu II polymorphism in intron 6. Gene fragments encompassing each
      polymorphic site were amplified by the polymerase chain reaction (PCR) and
      digested with an appropriate restriction enzyme whose recognition site was either
      naturally affected by the polymorphism or artificially created with a mismatched
      PCR-primer. According to the digestion profiles, genotypes were unambiguously
      distinguished. With this method, respective allelic frequencies were determined
      for 50 or 70 normal subjects. The procedure will facilitate LPL genotyping in the
      large population.

PMID- 1358996
TI  - Differential regulation of the expression of 3-hydroxy-3-methylglutaryl coenzyme
      A reductase, synthase, and low density lipoprotein receptor genes.
AB  - The ability of mitogenic stimulation of human T lymphocytes to alter the
      expression of genes involved in sterol metabolism was examined. Messenger RNA
      levels for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, HMG-CoA
      synthase, and low density lipoprotein (LDL) receptor were quantified in resting
      and mitogen-stimulated T lymphocytes by nuclease protection assay. Mitogenic
      stimulation increased HMG-CoA synthase mRNA levels by 5-fold and LDL receptor by
      4-fold when cells were cultured in lipoprotein-depleted medium whereas HMG-CoA
      reductase gene expression was not significantly increased. When cultures were
      supplemented with concentrations of low density lipoprotein sufficient to
      saturate LDL receptors, expression of all three genes was inhibited in resting
      lymphocytes, as effectively as was noted with fibroblasts. Similarly, LDL down
      regulated gene expression in mitogen-activated lymphocytes so that mitogenic
      stimulation did not increase either HMG-CoA reductase or synthase mRNA levels,
      although LDL receptor gene expression was enhanced. These results indicate that
      expression of three of the genes involved in sterol metabolism is differentially
      regulated by LDL and mitogenic stimulation. Moreover, the increase in rates of
      endogenous sterol synthesis and the activity of HMG-CoA reductase in mitogen
      stimulated T lymphocytes cannot be accounted for by increases in HMG-CoA
      reductase mRNA levels.

PMID- 1358997
TI  - Microfilaments, cell shape changes, and the formation of primary mesenchyme in
      sea urchin embryos.
AB  - Primary mesenchyme formation in sea urchin embryos occurs when a subset of
      epithelial cells of the blastula move from the epithelial layer into the
      blastocoel. The role of microfilaments in producing the cell shape changes that
      characterize this process, referred to as ingression, was investigated in this
      study. f-Actin was localized by confocal microscopy using labeled phalloidin. The
      distribution of f-actin was observed before, during, and after ingression and was
      correlated with cellular movements. Prior to the onset of ingression, staining
      became intense in the apical region of putative primary mesenchyme and
      disappeared following the completion of mesenchyme formation. The apical end of
      these cells constricted coincidentally with the appearance of the intensified
      staining, indicating that f-actin may be involved in this constriction. In
      addition, papaverine, a smooth muscle cell relaxant that interferes with
      microfilament-based contraction, and that was shown in this study to inhibit
      cytokinesis, diminished apical constriction and delayed ingression. Despite this
      interference with apical constriction, the basal surface of ingressing cells
      protruded into the blastocoel. It is suggested that apical constriction, while
      not necessary for ingression, does contribute to the efficient production of
      mesenchyme and that protrusion of the basal surface results from changes that
      occur independent of apical constriction.

PMID- 1358998
TI  - Dominant mutation of the murine Hox-2.2 gene results in developmental
      abnormalities.
AB  - Genes carrying the homeobox were originally identified in Drosophila, in which
      they are now known to play key roles in establishing segmentation patterns and in
      determining segment identities. A number of genes with striking homology to the
      Drosophila homeobox genes have now been found in the mouse genome, and mutational
      analysis is beginning to shed light on their function in mammalian development.
      To understand better the developmental significance of the murine Hox-2.2 gene,
      we have generated gain of function mutants by using the chicken beta-actin
      promoter to drive ubiquitous expression in transgenic mice. The resulting Hox-2.2
      misexpression produces early postnatal lethality as well as craniofacial and
      axial skeletal perturbations that include open eyes at birth, cleft palate,
      micrognathia, microtia, skull bone deficiencies, and structural and positional
      alterations in the vertebral column. We repeatedly observe complete or partial
      absence of the supraoccipital bone and malformations of the exoccipital and the
      basioccipital bones. These results suggests a role for the Hox-2.2 gene in
      specifying positional identity along the anterior-posterior axis.

PMID- 1358999
TI  - Dangerous marine life.
AB  - All physicians must be educated in treating injuries incurred when a diver comes
      into contact with any dangerous marine life. Stinging invertebrates are the most
      commonly encountered dangerous marine animals. Venomous vertebrate marine animals
      are less common than stinging invertebrates and easier to recognize. However,
      they may be much more deadly. Sharks pose the greatest danger to divers. However,
      bites from other marine animals can be painful, become infected and require
      extensive medical treatment.

PMID- 1359000
TI  - Receptive field properties of rod-driven horizontal cells in the skate retina.
AB  - The large receptive fields of retinal horizontal cells result primarily from
      extensive intercellular coupling via gap (electrical) junctions; thus, the extent
      of the receptive field provides an index of the degree to which the cells are
      electrically coupled. For rod-driven horizontal cells in the dark-adapted skate
      retina, a space constant of 1.18 +/- 0.15 mm (SD) was obtained from measurements
      with a moving slit stimulus, and a comparable value (1.43 +/- 0.55 mm) was
      obtained with variation in spot diameter. These values, and the extensive spread
      of a fluorescent dye (Lucifer Yellow) from the site of injection to neighboring
      cells, indicate that the horizontal cells of the all-rod retina of skate are well
      coupled electrically. Neither the receptive field properties nor the gap
      junctional features of skate horizontal cells were influenced by the adaptive
      state of the retina: (a) the receptive field organization was unaffected by light
      adaptation, (b) similar dye coupling was seen in both dark- and light-adapted
      retinae, and (c) no significant differences were found in the gap-junctional
      particle densities measured in dark- and light-adapted retinas, i.e., 3,184 +/-
      286/microns 2 (n = 8) and 3,073 +/- 494/microns 2 (n = 11), respectively.
      Moreover, the receptive fields of skate horizontal cells were not altered by
      either dopamine, glycine, GABA, or the GABAA receptor antagonists bicuculline and
      picrotoxin. We conclude that the rod-driven horizontal cells of the skate retina
      are tightly coupled to one another, and that the coupling is not affected by
      photic and pharmacological conditions that are known to modulate intercellular
      coupling between cone-driven horizontal cells in other species.

PMID- 1359001
TI  - Evidence of genomic variations between infectious pancreatic necrosis virus
      strains determined by restriction fragment profiles.
AB  - Infectious pancreatic necrosis virus (IPNV) is the aetiological agent of an
      important disease in hatchery-reared salmonid fish in North America, Europe and
      Japan. It belongs to the family Birnaviridae and shows a high degree of antigenic
      heterogeneity. However, genomic variations between the 10 identified serotypes
      have not yet been studied. In order to correlate genomic heterogeneity with the
      different serotypes, oligonucleotides were synthesized according to the published
      sequence of the Jasper strain (serotype A9). They were used as primers for the
      amplification of a 359 bp cDNA fragment of the viral genome using the polymerase
      chain reaction. Fragments amplified from 37 strains were digested with five
      different restriction enzymes. Restriction fragment profiles obtained an agarose
      gels showed heterogeneity not only between strains of different serotypes, but
      also among those belonging to serotype A1. A cluster analysis of the restriction
      patterns showed that IPNV strains can be divided into three major groups,
      corresponding approximately to serotypes A1, A2 and A3, and 10 subgroups which do
      not correlate with the serotyping of the strains.

PMID- 1359002
TI  - Demonstration of scrapie strain diversity in infected PC12 cells.
AB  - Scrapie strain replication in the nerve growth factor-induced, differentiated
      PC12 cell culture system was examined. Differences in replication between mouse
      derived agents were demonstrated, with the 139A scrapie strain yielding 100- to
      1000-fold higher levels of infectivity than the ME7 scrapie strain. Replication
      was not detected in PC12 cells infected with either the hamster-derived 263K or
      rat-derived 139R scrapie strains. Studies on the neurotransmitters in infected
      PC12 cells demonstrated that the adrenergic pathway was unchanged but the
      cholinergic pathway was altered. Furthermore, the degree of alteration correlated
      with the level of scrapie strain replication. Comparison of infectivity titres
      and enzymatic changes in ME7-infected PC12 cells with those in Chandler agent
      infected mouse neuroblastoma cells suggests that the significant changes in
      neurotransmitter levels in cultures exhibiting low titres of infectivity involve
      factors in addition to strain replication. The variation in the range of scrapie
      strain replication in PC12 cells is discussed in relationship to species barrier,
      cell targeting, genetic susceptibility and species strain specificity. These
      studies further emphasize the value of the PC12 cell model system in examining
      the scrapie strain-host cell interaction and in addition support the concept of
      variation among scrapie strains.

PMID- 1359003
TI  - Longitudinal outcome and medication noncompliance among manic patients with and
      without mood-incongruent psychotic features.
AB  - The prognostic utility of mood-incongruent psychotic features was examined in a
      sample of 23 hospitalized manic patients. Patients were initially subdivided
      according to whether they met Research Diagnostic Criteria (RDC) for
      schizoaffective, mainly affective (mood-incongruent) manic disorder (SAM; N = 11)
      or RDC primary manic (mood-congruent or nonpsychotic) manic disorder (PM; N =
      12). Patients were then followed over a 9-month posthospitalization period and
      rated every 3 months for relapse status, symptom severity, social adjustment, and
      medication noncompliance. Patients with SAM and PM did not differ at follow-up on
      rates or timing of manic or depressive relapses or on cycling of symptoms of mood
      disorder. However, at follow-up, SAM patients had more severe positive and
      negative psychotic symptoms and poorer social adjustment, and were less medically
      compliant than PM patients. Results are consistent with the view that mania with
      mood-incongruent psychotic features is a poor-prognosis subtype of bipolar
      disorder.

PMID- 1359004
TI  - Structure-activity relationship of the neurotransmitter alpha-bag cell peptide on
      Aplysia LUQ neurons: implications regarding its inactivation in the extracellular
      space.
AB  - Alpha-bag cell peptide [alpha-BCP (Ala-Pro-Arg-Leu-Arg-Phe-Tyr-Ser-Leu)] is a
      neurotransmitter that mediates bag cell-induced inhibition of left-upper-quadrant
      (LUQ) neurons L2, L3, L4, and L6 in the abdominal ganglion of Aplysia. Our recent
      biochemical studies have shown that alpha-BCP[1-9] is cleaved into alpha-BCP[1
      2], [3-9], [1-5], [6-9], and [7-9] by a combination of three distinct peptidase
      activities located within the extracellular spaces of the CNS: A diaminopeptidase
      IV (DAP-IV)-like enzyme cleaves alpha-BCP[1-9] at the 2-3 peptide bond; a neutral
      metalloendopeptidase (NEP)-like enzyme cleaves either alpha-BCP[1-9] or alpha
      BCP[3-9] at the 5-6 bond; an aminopeptidase M-II (APM-II)-like enzyme cleaves
      alpha-BCP[6-9] at the 6-7 bond, but cleaves neither alpha-BCP[1-9], nor the other
      ganglionic peptidase products. To further understand the manner in which alpha
      BCP is inactivated after release, that is loses its electrophysiological
      activity, we studied its structure-activity relationship by recording
      intracellularly from LUQ neurons in isolated abdominal ganglia that were
      arterially perfused with peptides dissolved in artificial sea water. The effects
      of alpha-BCP[1-9] and 15 of its fragments ([1-8], [1-7], [1-6], [1-5], [2-9], [3
      9], [3-8], [6-9], [7-9], [8-9], [6-7], [6-8], [1-2], Phe, Tyr) indicated that the
      sequence Phe6-Tyr7 was both necessary and sufficient to produce LUQ inhibitory
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359005
TI  - Transient expression of somatostatin peptide is a widespread feature of
      developing sensory and sympathetic neurons in the embryonic rat.
AB  - Previous studies from this and other laboratories demonstrated that many
      embryonic sensory ganglion cells in the rat transiently express the catecholamine
      synthesizing enzyme tyrosine hydroxylase (TH), a trait not expressed by most
      mature sensory neurons. We, therefore, sought to determine whether transient
      expression was uniquely associated with catecholaminergic traits, or,
      alternatively, whether embryonic ganglion cells transiently expressed peptidergic
      properties as well. Of the four peptides examined (somatostatin [somatotropin
      release inhibiting factor] (SRIF), galanin (Gal), calcitonin gene-related peptide
      (CGRP), and substance P (SP)), only SRIF was found to be transiently expressed
      during early stages of sensory gangliogenesis. Surprisingly, SRIF
      immunoreactivity was observed in virtually all cranial and spinal sensory
      ganglion cells on embryonic day (E) 12.5. In addition to perikaryal labeling,
      intense SRIF immunoreactivity was also observed in the central and peripheral
      processes of E12.5 sensory neurons, suggesting the peptide may be released from
      nerve endings. The time course of SRIF appearance in cranial ganglion cells
      paralleled that previously described for TH, and double-labeling studies revealed
      extensive co-localization of these two phenotypes. By E16.5, however, the number
      of neurons expressing SRIF had diminished markedly, indicating that SRIF is only
      transiently expressed by most sensory neurons during early stages of ganglion
      development. An unexpected finding was that transient expression of SRIF is also
      a prominent feature of sympathetic ganglion cells; however, the temporal pattern
      of staining in the sympathetic and sensory ganglia differed substantially.
      Whereas virtually no SRIF staining was observed in E12.5 sympathetics, the vast
      majority of cells in the E16.5 superior cervical ganglion (SCG) were labeled.
      This contrasted sharply with the adult SCG, in which only low levels of SRIF
      expression were found. These findings demonstrate that SRIF peptide is
      transiently expressed at high levels in peripheral sensory and sympathetic
      neurons during embryogenesis. The time course and widespread distribution of SRIF
      expression indicates that the peptide may play a role in early stages of ganglion
      cell growth and development. Moreover, these data, in conjunction with previous
      studies demonstrating SRIF immunoreactivity in developing central neurons,
      suggest that transient expression of this peptide is a common property of diverse
      neuronal cell types.

PMID- 1359006
TI  - Establishment of mouse-immortalized hybrid clones expressing characteristics of
      differentiated neurons derived from the cerebellar and brain stem regions.
AB  - Two clonal immortalized neurons designated CL8c4.7 and CL8a5.2 were established
      by somatic cell fusion between a hypoxanthine phosphoribosyltransferase-(HPRT-)
      deficient neuroblastoma N18TG2 and newborn mouse cerebellar/brain stem neurons.
      In the serum-containing medium without extra differentiating agents, both clones
      exhibited a morphology of differentiated neurons. They contained high levels of
      glutamate but no gamma-aminobutyric acid (GABA). The CL8a5.2 clone synthesized
      choline acetyltransferase and serotonin. In immunocytochemical studies, both
      clones expressed 200 kD neurofilament protein, neuron-specific enolase,
      microtubule-associated protein 2 (MAP2), tau protein, neuronal cell adhesion
      molecule (N-CAM), HNK-1, Thy-1.2, saxitoxin-binding sodium channel protein, and
      glutamate. Synaptophysin immunoreactivity was identified in the neuritic
      terminals of CL8c4.7 cells. Most of these antigens were barely detectable on
      N18TG2 cells. Electrophysiologically, both clones generated action potentials in
      response to electrical stimuli. The hybrid clones that express characteristics of
      differentiated neurons derived from the cerebellar and brain stem regions might
      be invaluable for the study of the molecular basis of neuronal differentiation
      and degeneration in these regions.

PMID- 1359007
TI  - Toxicity and residual action of the photoactivated compound, cyano-alpha
      terthienyl, and its efficacy for reducing pre-imaginal populations of mosquitoes.
AB  - The photoactivated compound, cyano-alpha-terthienyl (cyano-alpha-T), was highly
      toxic to pre-imagines of the mosquitoes Culex restuans, Cx. tarsalis and Culiseta
      inornata when synergized with piperonyl butoxide (PBO). Lethal concentrations for
      50% mortality, determined during an outdoor trial using caged fourth-instar Culex
      spp. larvae, were 19.4, 15.4 and 12.9 g/ha at 24, 48 and 72 h after treatment,
      respectively. No residual activity of cyano-alpha-T was observed beyond 24 h
      following treatment. In artificial pool tests, greatest population reductions
      were achieved using dosages of 20 and 40 g/ha; statistically significant
      reductions were not observed following applications of 5 g/ha. Cyano-alpha-T plus
      PBO was more effective for reducing mosquito populations than alpha-terthienyl
      (alpha-T) plus PBO at comparable dosages, although it exhibited slightly lower
      insecticidal activity at a dosage of 20 g/ha than a formulation of Bacillus
      thuringiensis var. israelensis (Vectobac 12 AS, 0.12 ml/m2). Greatest
      effectiveness of cyano-alpha-T plus PBO was observed in pools with low organic
      content relative to pools high in organic content.

PMID- 1359009
TI  - Occurrence of Psorophora howardii in Suffolk County, Long Island, New York.
AB  - Psorophora howardii has been confirmed in New York State for the first time,
      based on larvae from a rain pool and an adult female from a CDC trap catch. Both
      collections were reported from Suffolk County, Long Island, NY.

PMID- 1359008
TI  - New state record for Culiseta impatiens in Maryland.
AB  - Culiseta impatiens is reported for the first time from Maryland. Collections from
      the southwestern border of Fort George G. Meade extend the range of this species
      over 400 km farther south than previous records. Multiple collections from 4
      separate traps during 2 years indicate a population of Cs. impatiens is probably
      established in the collection area.

PMID- 1359010
TI  - 10th International Conference on Iron and Iron Proteins. Oxford, United Kingdom,
      July 27-31, 1992.

PMID- 1359011
TI  - Regulation of expression of dopamine beta-hydroxylase in PC12 cells by
      glucocorticoids and cyclic AMP analogues.
AB  - Regulation of catecholamine biosynthesis is crucial in the adaptation to various
      physiological conditions, such as stress, and in several disorders, including
      hypertension and depression. In this study we have found that in PC12 cells, the
      mRNA levels of dopamine beta-hydroxylase (DBH), the enzyme that catalyzes the
      formation of norepinephrine from dopamine, can be regulated by glucocorticoids
      and cyclic AMP (cAMP) analogues. Treatment with dexamethasone increased DBH mRNA
      levels by 6 h. with maximal elevation (four- to fivefold) obtained after 1 day of
      exposure, and these levels were maintained for up to 4 days. DBH mRNA levels were
      also elevated on treatment of PC12 cells with 8-bromo cAMP for 8 h to 1 day. The
      response to 8-bromo cAMP, however, was bimodal, because DBH mRNA levels declined
      below control values on treatment for > 1 day. In combined treatments with 8
      bromo cAMP and dexamethasone, the cAMP effect was dominant. To begin to
      characterize the regulation of DBH mRNA, genomic clones for rat DBH were
      isolated, and 1 kb of the 5' flanking region was sequenced. Several putative
      regulatory elements, which may be involved in cAMP and glucocorticoid regulation,
      were identified, including two adjacent cAMP response elements, another element
      that can also bind members of the ATF/CREB family of transcription factors, a NF
      kappa B-like sequence, several AP-2 sites, and three core glucocorticoid receptor
      binding sequences.

PMID- 1359012
TI  - Tetrahydrobiopterin turnover in cultured rat sympathetic neurons: developmental
      profile, pharmacologic sensitivity, and relationship to norepinephrine synthesis.
AB  - We have examined the turnover of 5,6,7,8-tetrahydrobiopterin (BH4) and the effect
      of decreasing BH4 levels on in situ tyrosine hydroxylase (TH) activity and
      norepinephrine (NE) content in a homogeneous population of NE-containing neurons
      derived from the superior cervical ganglion (SCG) of the neonatal rat and
      maintained in tissue culture. Initial studies indicated that the level of BH4
      within SCG cultures increased fourfold between 5 and 37 days in vitro (DIV). This
      increase in BH4 levels was determined to result from an increase in the rate of
      BH4 biosynthesis without a change in the rate of degradation. Regardless of
      culture age, the BH4 content of SCG neurons was observed to turn over with a half
      life of approximately 2.5 h. BH4 synthesis by SCG neurons was found to be five
      times more sensitive to inhibition by 2,4-diamino-6-hydroxypyrimidine (DAHP) and
      25 times less sensitive to inhibition by N-acetylserotonin than was previously
      reported for CNS neurons in culture. Under basal conditions, the rates of in situ
      TH activity and BH4 biosynthesis were similar. In response to inhibition of BH4
      biosynthesis by DAHP and a 90-95% decrease in BH4 levels, in situ TH activity
      declined by 75%. NE levels declined by 30% following a 24-h period of inhibition
      of BH4 synthesis. After 2 days of BH4 synthesis inhibition, the level of NE was
      decreased by 47%. On treatment days 3 and 4, the decline in NE content plateaued
      at 24% of control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359013
TI  - Stimulation of cultured cerebellar granule cells via glutamate receptors induces
      TRE- and CRE-binding activities mediated by common DNA-binding complexes.
AB  - By use of nuclear mini-extracts prepared from cultured cerebellar granule cells
      in a gel-mobility assay, exogenous N-methyl-D-aspartate (NMDA) or kainate was
      shown to increase both 12-O-tetradecanoylphorbol 13-acetate-responsive element
      (TRE)- and cyclic AMP-responsive element (CRE)-binding activity. These increases
      were specifically prevented by the NMDA receptor antagonist D,L-2-amino-5
      phosphonovalerate and the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline
      2,3-dione, respectively. The increase of TRE-binding activity was dependent on de
      novo protein synthesis, and its inductions by both NMDA and kainate required
      extracellular Ca2+. TRE-binding activity was competitively inhibited by the CRE,
      and vice versa, showing higher DNA-binding affinity to the CRE than to the TRE. A
      proteolytic clipping bandshift assay demonstrated that the increase in CRE
      binding activity could be mediated by the TRE-binding activity. Thus, the TRE
      binding activity cross-binding to the CRE could be activated by NMDA or kainate
      stimulation. The involvement of c-Fos or Fos-related proteins in the TRE- and CRE
      binding complexes was shown by a supershift gel-mobility assay using anti-c-Fos
      antiserum.

PMID- 1359014
TI  - Biphasic 24-hour variations in cyclic GMP accumulation in the rat pineal gland
      are due to corresponding changes in the activity of cytosolic and particulate
      guanylate cyclase.
AB  - Various parameters of the rat pineal gland display a 24-h rhythm. However,
      nothing is known about possible 24-h variations in cyclic GMP (cGMP) metabolism.
      In the present study, 24-h variations in pineal gland cGMP accumulation were
      investigated by determining the increase in cGMP level with and without
      inhibitors of phosphodiesterase at different time points over a light/dark cycle
      (12/12 h). Furthermore, the activity of guanylate cyclase (GC) was determined
      under substrate-saturated conditions regarding the cytosolic and particulate
      forms of the enzyme. It has been found that cGMP accumulation and GC activity
      display biphasic 24-h variations with two peaks--one approximately 7 h after
      lights "on" and the other approximately 7 h after lights "off." The activity of
      cytosolic GC remains unchanged in the presence of the nitric oxide (NO) synthesis
      inhibitor N-monomethyl-L-arginine, indicating that 24-h variations in the
      activity do not reflect changes in the synthesis of the GC stimulator NO.

PMID- 1359015
TI  - Neomycin is an agonist at a polyamine site on the N-methyl-D-aspartate receptor.
AB  - Neomycin appears as a full agonist and spermidine as a partial agonist at the
      site where polyamines enhance 1-[1-(2-thienyl)cyclohexyl][3H]piperidine ([3H]TCP)
      binding on the N-methyl-D-aspartate (NMDA) receptor. Other aminoglycosides also
      enhance [3H]TCP binding with efficacies roughly proportional to the number of
      primary amine groups. The polyamine antagonists ifenprodil and arcaine inhibit
      enhancement of [3H]TCP binding by spermidine or neomycin. The inhibition of
      [3H]TCP binding by arcaine is apparently competitively reduced by neomycin and
      spermidine, supporting a common site. Diethylenetriamine (previously described as
      a polyamine antagonist) may be a partial agonist. Enhancement by neomycin or
      spermidine is not additive to that of Mg2+, consistent with competition of Mg2+
      and spermidine or neomycin at the site where these compounds enhance [3H]TCP
      binding. Polyamines also enhance the binding of the competitive antagonist 2-(2
      carboxypiperazin-4-yl)[3H]propyl-1-phosphonic acid ([3H]CPP). Neomycin, which
      does not enhance [3H]CPP binding, inhibits the enhancement by spermidine. That
      this site is distinct from the site where spermidine and neomycin increase
      [3H]TCP binding is supported by different pharmacology. Arcaine and
      diethylenetriamine do not inhibit spermidine enhancement of [3H]CPP binding. Mg2+
      also does not compete with the spermidine enhancement of [3H]CPP binding.
      Ifenprodil inhibits the spermidine enhancement of [3H]CPP binding. The data
      suggest two or more polyamine sites, with arcaine selective for the site that
      enhances [3H]TCP binding. Neomycin is an agonist at one polyamine site and
      antagonist to the second.

PMID- 1359016
TI  - Differential effects of tetanus toxin on inhibitory and excitatory
      neurotransmitter release from mammalian spinal cord cells in culture.
AB  - The effect of tetanus toxin on depolarization-evoked and spontaneous synaptic
      release of inhibitory and excitatory neurotransmitters was examined in murine
      spinal cord cell cultures. Toxin action on the release of radiolabeled glycine
      and glutamate was followed over time intervals corresponding to the early phase
      of convulsant activity through the later phase of electrical quiescence. Tetanus
      toxin inhibited potassium-evoked release of [3H]glycine and [3H]glutamate in a
      time- and dose-dependent manner. Ninety minutes after the application of toxin (6
      x 10(-10) M), the stimulated release of [3H]glycine was blocked completely,
      whereas stimulated release of [3H]glutamate was not blocked completely until 150
      210 min after toxin application. Fragment C, the binding portion of the tetanus
      toxin molecule, had no effect on stimulated release of either transmitter. The
      spontaneous synaptic release of [3H]glycine was blocked totally within 90 min of
      toxin exposure. In contrast, the spontaneous release of [3H]glutamate, in toxin
      exposed cultures, was elevated to nearly twice that of control cultures at this
      time. Thus, toxin-induced convulsant activity is characterized by a reduction in
      the spontaneous synaptic release of inhibitory neurotransmitter with a
      concomitant increase in the release of excitatory neurotransmitter, as well as
      the more rapid onset of blockade of depolarization-evoked release of inhibitory
      versus excitatory neurotransmitter.

PMID- 1359017
TI  - Neuropeptide Y inhibits beta-adrenergic agonist- and vasoactive intestinal
      peptide-induced cyclic AMP accumulation in rat pinealocytes through pertussis
      toxin-sensitive G protein.
AB  - The effects of neuropeptide Y (NPY) on pineal gland cyclic AMP (cAMP)
      accumulation were investigated using dispersed pinealocytes from rats. NPY
      inhibited the intracellular cAMP accumulation stimulated by isoproterenol and
      norepinephrine in a dose-dependent manner during a 10-min incubation of
      pinealocytes. NPY (1 x 10(-7) M) also inhibited vasoactive intestinal peptide
      (VIP)- and cholera toxin-induced cAMP accumulation. The inhibitory effect of NPY
      on isoproterenol-induced cAMP accumulation was completely abolished by a 5-h
      pretreatment of pinealocytes with 1 microgram/ml of pertussis toxin (PT). These
      results suggest that NPY participates in modulation of cAMP production in the rat
      pineal gland through PT-sensitive G protein. Yohimbine, an alpha 2-adrenergic
      antagonist, blocked NPY inhibition of isoproterenol-stimulated cAMP accumulation.
      On the other hand, the alpha 2-adrenergic agonist clonidine by itself did not
      affect cAMP accumulation stimulated by isoproterenol but significantly
      potentiated NPY action. The present study demonstrates that NPY inhibits beta
      adrenergic or VIPergic stimulation of the pineal gland cAMP accumulation. The
      inhibitory effect of NPY is mediated through PT-sensitive G protein. Our results
      also suggest that NPY exerts its action to affect alpha 2-adrenoceptor function.

PMID- 1359019
TI  - Nicotinic cholinergic regulation of tyrosine hydroxylase gene expression and
      catecholamine synthesis in isolated bovine adrenal chromaffin cells.
AB  - Isolated bovine adrenal chromaffin cells were used to study the nicotinic
      regulation of tyrosine hydroxylase (TH) gene expression. Continuous exposure of
      the cells to carbachol or the nicotinic receptor agonist 1,1-dimethyl-4
      phenylpiperazinium (DMPP) produces a time- and concentration-dependent increase
      in TH enzyme activity, whereas muscarine has no effect. DMPP at 1 microM (EC50 =
      0.3 microM) elicits a two- to threefold elevation of both TH activity and TH
      immunoreactive protein level after 3-5 days in the presence of 2.5 mM calcium;
      the increase in enzyme levels is significantly less at lower extracellular
      calcium levels. The rate of hydroxylation of tyrosine to dopamine (DA) in intact
      cells, an index of endogenous TH activity, increases in parallel with the rise in
      TH levels. The TH mRNA level is elevated before the increase in protein levels.
      As determined by nuclear run-on assays, TH gene transcription is stimulated two-
      to threefold within 30 min of addition of 1 microM DMPP to the cells;
      transcription returns to basal levels by 2 h. Nitrendipine (20 microM) blocks the
      stimulation of transcription by DMPP. Pretreatment of the cells with
      cycloheximide (5 microM) does not prevent the DMPP stimulation of transcription.
      Forskolin (10 microM) also increases TH transcription (fourfold in 15 min) by a
      mechanism that is not blocked by cycloheximide. These results show that nicotinic
      receptor stimulation increases TH mRNA synthesis, TH protein levels, and TH
      activity in a calcium-dependent manner. Furthermore, the nicotinic influence on
      TH gene expression does not appear to require the synthesis of a protein factor
      for its effects. That in situ DA synthesis rates are elevated consequent to the
      rise in TH levels demonstrates that TH induction serves as a mechanism for
      enhancing the catecholamine-synthesizing capacity of the chromaffin cell on a
      long-term basis.

PMID- 1359020
TI  - Taxol: quantitative internuclear proton-proton distances in CDCl3 solution from
      nOe data: 2D nmr ROESY buildup rates at 500 MHz.
AB  - Quantitative nmr internuclear proton-proton distance measurements obtained by
      observation of the initial buildup rates of nOe's in 2D ROESY spectra of taxol
      [1] in CDCl3 are reported. A comparison to the X-ray crystal structure of
      taxotere [2] is made, and the results are discussed in terms of previous studies
      of structure-activity relationships.

PMID- 1359018
TI  - Differing neurochemical and morphological sequelae of global ischemia: comparison
      of single- and multiple-insult paradigms.
AB  - The purpose of this investigation was to investigate pathomechanisms responsible
      for the deleterious effects of repeated episodes of brief forebrain ischemia.
      Halothane-anesthetized male Wistar rats were subjected to either (a) a single 15
      min period or (b) three 5-min periods (separated by 1 h) of global forebrain
      ischemia by bilateral carotid artery occlusions plus hypotension (50 mm Hg),
      followed by various periods of recirculation. Brain temperature was normothermic
      throughout. In one series of rats, extracellular levels of glutamate, glycine,
      and gamma-aminobutyric acid (GABA) were measured in the dorsolateral striatum (n
      = 6-8 per group) and lateral thalamus (n = 4-6 per group) by microdialysis and
      HPLC before and during ischemia and during 3-5 h of recirculation. In a parallel
      series of rats (n = 6 per group), ischemic cell change was quantified at 2 (dark
      neurons), 24, or 72 h following either single or multiple ischemic insults. A
      single 15-min ischemic period led to massive glutamate release (13-fold increase;
      p = 0.001), which returned to normal by 20-30 min of recirculation and remained
      normal thereafter. By contrast, in rats with three 5-min periods of ischemia, the
      glutamate level rise with each repeated insult (four- to 4.5-fold; p < or = 0.02)
      was smaller than that observed during the single 15-min insult, but a late
      sustained rise (five- to six-fold; p < 0.05) occurred at 2-3 h of recirculation.
      Brief ischemia-induced elevations of glycine and GABA levels were detected in
      both the single- and multiple-insult groups, with normalization during
      recirculation. In contrast, the excitotoxic index, a composite measure of
      neurotransmitter release ([glutamate] x [glycine]/[GABA]), differed markedly
      following single versus multiple insults (p = 0.002 by repeated-measures analysis
      of variance) and increased by seven- to 12-fold (p < 0.05) at 1-3 h following the
      third insult. The total amount of glutamate released was 3.3-fold higher in the
      multiple-insult than in the single-insult group (p < 0.02). At 2 h of
      recirculation, histopathological analysis of dorsolateral striatum showed a
      significantly greater frequency of dark neurons in the multiple- than in the
      single-insult group (p < 0.05 by analysis of variance). In the thalamus, a higher
      frequency of ischemic neurons was seen in the multiple-than in the single-insult
      group at all intervals studied. Thus, in rats with multiple ischemic insults,
      accelerated ischemic damage was found in the striatum, and severe ischemic injury
      was documented in the thalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1359021
TI  - An immunogenetic heterogeneity in multiple sclerosis.
AB  - Two clinical forms of multiple sclerosis (MS), primarily chronic progressive MS
      (PCP MS) and relapsing/remitting MS (R/R MS) have been shown to differ in several
      respects. The results of genomic HLA class II typing with restriction fragment
      length polymorphism analysis of 62 MS patients from Western Norway, 42 with R/R
      MS and 20 PCP MS, are reported on here. As in previous studies of Swedish
      patients, the haplotype DRw17(3), DQw2 was found to be five times more common in
      R/R MS than in PCP MS. This finding supports the hypothesis that R/R and PCP MS
      are immunogenetically separate entities. In contrast with a previous
      investigation of Norwegian MS patients, no association of MS with glutamine at
      position 34 of the HLA-DQ alpha chain or with defined sequences of the HLA-DQB1
      gene was found.

PMID- 1359022
TI  - Determinants of total high density lipoprotein cholesterol and high density
      lipoprotein subfraction levels among Hispanic and non-Hispanic white persons with
      normal glucose tolerance: the San Luis Valley Diabetes Study.
AB  - Determinants of total high-density lipoprotein cholesterol (HDL-C) and HDL
      subfractions were assessed in Hispanic and non-Hispanic white persons (n = 932),
      aged 20-74 years, in the San Luis Valley, Colorado. Using multiple regression,
      BMI was negatively associated with HDL-C, HDL2-C, and HDL3-C in men and HDL-C and
      HDL3-C in women. Among females, current smokers had lower HDL-C and subfractions.
      Women on beta-blockers had lower HDL3-C levels. For both sexes, a positive
      association was observed between age and HDL-C and subfractions and physical
      activity with HDL-C and HDL3-C. Drinking alcohol (> or = 50 g/week) was
      associated with higher HDL-C and HDL3-C in both sexes and HDL2-C in women. The
      positive association of age and negative associations of the subscapular/triceps
      ratio and fasting insulin had consistent relationships with HDL-C, HDL2-C, and
      HDL3-C in men and women. Ethnicity was not significantly associated with HDL-C or
      subfractions after controlling for body fat distribution or fasting insulin.

PMID- 1359023
TI  - The action of the putative neurotransmitters N-acetylaspartylglutamate and L
      homocysteate in cat dorsal lateral geniculate nucleus.
AB  - 1. We have examined the actions and pharmacology of two putative optic nerve
      transmitters, N-acetylaspartylglutamate (NAAG) and L-homocysteic acid (L-HCA), in
      the feline dorsal lateral geniculate nucleus (dLGN). We compared the responses
      obtained to iontophoretic application of these substances with those elicited by
      visual stimulation and application of specific N-methyl-D-aspartate (NMDA) and
      non-NMDA receptor agonists. The relative effects of the selective NMDA antagonist
      3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) and the
      selective non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were
      tested on these responses. 2. There was a pronounced contrast between the
      influence of iontophoretically applied NAAG and L-HCA on dLGN cells.
      Iontophoretic application of NAAG [ejection current range 75-200 nA (mean 125
      nA)] evoked either no effect (17/37), or very weak and sluggish excitatory
      (16/37) or inhibitory (4/37) effects. Conversely, L-HCA application [current
      range 25-136 nA (mean 67 nA)] elicited brisk and powerful excitatory responses
      (32/32) that were comparable with those produced by visual stimulation and
      iontophoresis of NMDA, kainate, and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA). 3. Responses to L-HCA were selectively
      antagonized by application of the NMDA receptor antagonist CPP but were generally
      much less affected by the non-NMDA receptor antagonist CNQX. The weak and
      inconsistent responses to NAAG were not compatible with an evaluation of
      antagonist effects. 4. CPP application at dose levels selective for NMDA with
      respect to kainate and AMPA did not exert equal effects on L-HCA and NMDA.
      Whereas the mean responses to L-HCA were reduced to 32% of control for Y cells
      and 21% for X cells, those to NMDA were 11 and 11%, respectively. However, the
      level of reduction of the visual response for X and Y cells was very similar to
      that of L-HCA, visual responses being reduced to 35 and 22% of control for Y and
      X cells. 5. CNQX application reduced the visual response level of Y cells to 64%
      of control and that of X cells to 65%. The mean level for the L-HCA response of Y
      cells was 106% of control; the mean for X cells, 79%, was substantially below
      control. The responses to kainate and AMPA were reduced to a much greater extent.
      6. The data suggest that it is unlikely that NAAG is the optic nerve
      transmitter.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1359024
TI  - Dopamine and glutamate agonists stimulate neuron-specific expression of Fos-like
      protein in the striatum.
AB  - 1. The monoamine dopamine and the amino acid glutamate are major
      neurotransmitters in the basal ganglia implicated in the normal functions of the
      striatum and in extrapyramidal disease states. To study the effects of these
      neurotransmitters on gene transcription in striatal neurons, we treated rats with
      dopamine (monoamine) agonists and with glutamate agonists and monitored the
      induction of Fos-like protein in striatal neurons. We administered the indirect
      monoamine agonists cocaine and amphetamine intraperitoneally and gave the
      glutamate agonist quinolinic acid by direct intrastriatal injection. We
      identified the phenotypes of the responsive neurons by immunohistochemistry and
      by enzyme histochemistry in double staining protocols. 2. Both the indirect
      monoamine agonists and the glutamate receptor agonist stimulated rapid nuclear
      expression of Fos-like protein in specific classes of striatal neurons. The
      induction by cocaine and amphetamine was blocked by pretreatment with the
      dopamine D1-like receptor antagonist SCH23390, and the induction by quinolinic
      acid was blocked by pretreatment with MK-801, a noncompetitive antagonist of the
      N-methyl-D-aspartate (NMDA) glutamate receptor. 3. The monoamine and glutamate
      agonists both induced Fos-like protein exclusively in striatal neurons that
      constitutively expressed the protein phosphatase inhibitor DARPP-32 (dopamine and
      cAMP-regulated phosphoprotein). 4. The dopamine agonists failed to induce
      detectable Fos-like protein in striatal neurons expressing enkephalin, even
      though many such neurons expressed DARPP-32. By contrast, many enkephalinergic
      neurons did express Fos-like protein in response to glutamatergic stimulation. 5.
      Glutamate agonist stimulation, but not dopamine agonist stimulation, induced Fos
      like protein in a subpopulation of striatal interneurons, namely, a group of
      neurons exhibiting NADPH-diaphorase activity. 6. These findings suggest that
      stimulation of dopamine D1-like receptors (or related monoamine receptors) and
      glutamate NMDA receptors activates neuron-specific programs of immediate-early
      gene expression in the striatum. Our findings further suggest that monoamine and
      glutamate may act cooperatively at the transcriptional level on a functionally
      defined subset of striatal neurons.

PMID- 1359025
TI  - Blockade of excitation reveals inhibition of dentate spiny hilar neurons recorded
      in rat hippocampal slices.
AB  - 1. Extracellular and intracellular recordings in rat hippocampal slices were used
      to compare the synaptic responses to perforant path stimulation of granule cells
      of the dentate gyrus, spiny "mossy" cells of the hilus, and area CA3c pyramidal
      cells of hippocampus. Specifically, we asked whether aspects of the local
      circuitry could explain the relative vulnerability of spiny hilar neurons to
      various insults to the hippocampus. 2. Spiny hilar cells demonstrated a
      surprising lack of inhibition after perforant path activation, despite robust
      paired-pulse inhibition and inhibitory postsynaptic potentials (IPSPs) in
      adjacent granule cells and area CA3c pyramidal cells in response to the same
      stimulus in the same slice. However, when the slice was perfused with excitatory
      amino acid antagonists [6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), or CNQX
      with 2-amino-5-phosphonovaleric acid (APV)], IPSPs could be observed in spiny
      hilar cells in response to perforant path stimulation. 3. The IPSPs evoked in
      spiny hilar cells in the presence of CNQX were similar in their reversal
      potentials and bicuculline sensitivity to IPSPs recorded in dentate granule cells
      or hippocampal pyramidal cells in the absence of CNQX. 4. These results
      demonstrate that, at least in slices, perforant path stimulation of spiny hilar
      cells is primarily excitatory and, when excitation is blocked, underlying
      inhibition can be revealed. This contrasts to the situation for dentate and
      hippocampal principal cells, which are ordinarily dominated by inhibition, and
      only when inhibition is compromised can the full extent of excitation be
      appreciated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359026
TI  - Mu opioid receptor-mediated modulation of synaptic currents in dentate granule
      cells of rat hippocampus.
AB  - 1. The effect of a selective mu opioid agonist, [N-MePhe3-D-Pro4]morphiceptin
      (PL017), on synaptic transmission in the dentate gyrus was examined in
      hippocampal slices. Synaptic currents were evoked by stimulation of the outer
      molecular layer and recorded from granule cells using whole-cell voltage-clamp
      techniques. 2. Monosynaptic inhibitory postsynaptic currents (IPSCs) were evoked
      in the presence of D(-)-2-amino-5-phosphonovaleric acid (D-APV), and N-methyl-D
      aspartate (NMDA) receptor antagonist, and 6,7-dinitroquinoxaline-2,3-dione
      (DNQX), a non-NMDA type of glutamate receptor antagonist. The IPSCs consisted of
      a gamma-aminobutyric acid (GABA)A receptor-mediated early component and a GABAB
      receptor-mediated late component. 3. Bath application of PL017 (0.3-3 microM)
      induced a dose-dependent reduction in the amplitude of both early IPSCs (21-56%)
      and late IPSCs (43-81%). These effects could be reversed by the opiate antagonist
      naloxone (1 microM) or prevented by the selective mu antagonist beta
      funaltrexamine hydrochloride (10 microM). 4. NMDA receptor-mediated excitatory
      postsynaptic currents (EPSCs) were revealed in the presence of DNQX and the GABAA
      antagonist bicuculline methiodide. PL017 (3 microM) caused a 35% reduction in the
      amplitude of NMDA EPSCs. NMDA receptor-mediated population EPSPs recorded
      extracellularly were also inhibited by 3 microM PL017 to a similar degree. 5. Non
      NMDA receptor-mediated EPSCs were demonstrated in the presence of D-APV and
      bicuculline methiodide. The amplitude of non-NMDA EPSCs was not affected by
      PL017.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359027
TI  - Calcium transients evoked by climbing fiber and parallel fiber synaptic inputs in
      guinea pig cerebellar Purkinje neurons.
AB  - 1. Calcium transients related to climbing fiber (CF) and parallel fiber (PF)
      synaptic potentials were recorded from Purkinje cells in guinea pig cerebellar
      slices. Transients were measured using either absorbance changes of arsenazo III
      or fluorescence changes of fura-2, which were injected into individual cells in
      the slice. 2. All-or-none somatically recorded CF potentials elicited by white
      matter stimulation had all-or-none Ca transients. These signals began with a
      delay of > or = 2 ms from the start of the electrically recorded synaptic
      potential. The recovery time of CF-induced arsenazo III absorbance transients was
      < 50 ms in the fine dendrites in conditions that minimized the effects of dye
      buffering. 3. Ca2+ entry through voltage-gated Ca channels opened by Ca action
      potentials was the dominant source of the rise in [Ca2+]i after CF activation.
      There was no significant change in [Ca2+]i corresponding to the plateau potential
      that followed the large CF response. 4. The appearance and amplitude of distal CF
      evoked Ca signals was more variable than proximal signals, suggesting that CF
      potentials do not reliably spread to the fine distal dendrites. The distal
      transient could be enhanced by intrasomatic depolarizing pulses, suggesting that
      it was a property of the postsynaptic membrane and not the presynaptic side of
      the CF synapse that was responsible for this variability. 5. Parallel fiber
      responses were evoked by electrical stimulation near the pial surface. Graded
      synaptic potentials and related Ca transients were reversibly blocked by 2 microM
      6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Small synaptic potentials induced
      small, localized Ca transients. With increasing stimulus intensity, the PF
      electrical response developed a regenerative component. Larger dendritic Ca
      transients were detected corresponding to this component. Ca transients evoked by
      the regenerative responses had the same rapid rise times and fall times as those
      related to somatically stimulated Ca action potentials, suggesting that they also
      were due to Ca2+ entry through voltage-sensitive channels. 6. During trains of PF
      responses, we observed an increase in the spatial extent of related Ca
      transients. This effect could be modulated by changes in the resting potential,
      suggesting that the same intrinsic mechanism was affecting the spread of both CF
      and PF signals.

PMID- 1359029
TI  - Fibroblast growth factor differentially modulates the neurotransmitter phenotype
      of cultured sympathetic neurons.
AB  - Fibroblast growth factors (FGFs) are multifunctional growth factors that increase
      the proliferation of mesoderm- and neuroectoderm-derived cells and promote
      neuronal survival and neurite outgrowth in various regions of the brain, yet the
      physiological role(s) they may play in nervous system function and/or development
      is unclear. The present report demonstrates, using a well-characterized system,
      avian sympathetic neurons in vitro, that acidic and basic FGFs increase ChAT but
      decrease tyrosine hydroxylase (TH) activity in these cells, without affecting
      neuronal growth and survival. Heparin, which binds to FGFs with a high affinity,
      potentiates the activity of FGF on ChAT, but not TH. The time course of FGF
      action on the neurotransmitter phenotype is slow since effects start to appear
      after 1-2 d only. FGFs may thus modulate the activities of ChAT and TH by
      differentially regulating the expression of the genes coding for these enzymes.
      In conclusion, this report provides evidence supporting the hypothesis that FGFs
      may play a role in regulating neurotransmitter expression in sympathetic neurons
      during development independently of any effect on neuronal survival.

PMID- 1359028
TI  - Membrane properties of mesopontine cholinergic neurons studied with the whole
      cell patch-clamp technique: implications for behavioral state control.
AB  - 1. The whole-cell patch-clamp technique was used to study the membrane properties
      of identified cholinergic and noncholinergic laterodorsal tegmental neurons in
      slices of rat brain maintained in vitro. 2. On the basis of their expression of
      the transient outward potassium current IA and the transient inward calcium
      current IT, three classes of neurons were observed: type I neurons exhibited a
      large IT; type II neurons exhibited a prominent IA; and type III neurons
      exhibited both IA and IT. 3. Combining intracellular deposition of biocytin with
      NADPH diaphorase histochemistry revealed that the vast majority of type III
      neurons were cholinergic, whereas only a minority of type I and type II neurons
      were cholinergic. Thus mesopontine cholinergic neurons possess intrinsic ionic
      currents capable of inducing burst firing. 4. Delineation of the intrinsic
      membrane properties of identified mesopontine cholinergic neurons, in concert
      with recent results regarding the responses of these neurons to neurotransmitter
      agents, has led us to present a unifying and mechanistic hypothesis of brain stem
      cholinergic function in the control of behavioral states.

PMID- 1359030
TI  - Calcium concentration dynamics produced by synaptic activation of CA1 hippocampal
      pyramidal cells.
AB  - The spatial and temporal dynamics of many electrophysiological and biochemical
      processes in nerve cells are in turn dependent on the concentration dynamics of
      the second messenger calcium. We have used microfluorimetry of the calcium
      indicator fura-2 (Grynkiewicz et al., 1985) to measure and characterize
      synaptically activated calcium changes in individual CA1 pyramidal cells
      contained within guinea pig hippocampal slices. One component of the calcium
      changes was largely produced by influx through voltage-dependent Ca2+ channels
      (VDCCs). It consisted of large transient accumulations in the proximal-apical and
      basal dendrites; the amplitude was smaller in the distal-apical dendrites and the
      soma. This spatial profile was insensitive to the method of cell activation:
      stimulation of inputs located at different positions on the dendritic tree as
      well as antidromic stimulation produced only slight modifications. This component
      was not blocked by the NMDA antagonist 5-amino-4-phosphonovalerate (AP5)
      (Collingridge et al., 1983), was greatly reduced by Cd2+, partially reduced by
      nifedipine, and was increased by Bay-K 8644, providing the evidence that it was
      largely produced by influx through VDCCs. Blocking postsynaptic Na+ channels with
      QX-314 greatly reduced the accumulation amplitude, and spatial differences
      between proximal-dendritic and distal-dendritic regions were less pronounced,
      suggesting that active sodium conductances contribute significantly to the
      spatial activation of calcium conductances. Residual spatial differences that
      persist in QX-314 experiments are consistent with the idea that VDCCs have
      decreased density on distal-apical dendrites. A second component of accumulation
      was induced by ionic currents through NMDA receptor channels. It was blocked by
      AP5, unaffected by QX-314, attenuated and slowed down by elevated calcium
      buffering, and spatially localized to regions receiving activated synaptic
      inputs. The magnitude of this component was strongly dependent on the frequency
      and amplitude of synaptic activation. At high frequency, it was generally very
      large, often saturating the fura-2 (> 2 microM). Measurements made with the
      indicator furaptra also showed large localized AP5-sensitive fluorescence
      changes. Our results suggest that in dendritic regions near activated input
      fibers calcium levels may reach 2-10 microM. In general, our measurements of
      calcium dynamics provide an experimental basis for evaluating the spatial
      distribution of calcium conductances, the spatial distribution of calcium
      activated electrophysiological and biochemical processes, and the spatial
      uniformity of calcium buffering and removal systems in CA1 hippocampal pyramidal
      cells. The time course and amplitude of Ca2+ transients we measured suggest that
      activation of Ca(2+)-dependent conductances [e.g., IK(Ca)] will be markedly
      different for different cellular regions.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1359031
TI  - Long-term synaptic depression in the striatum: physiological and pharmacological
      characterization.
AB  - The effect of tetanic activation of corticostriatal glutamatergic fibers was
      studied in striatal slices by utilizing extracellular and intracellular recording
      techniques. Tetanic stimulation produced a long-term synaptic depression (LTD) (>
      2 h) of both extracellularly recorded field potentials and intracellularly
      recorded EPSPs. LTD was not coupled with changes of intrinsic membrane properties
      of the recorded neurons. In some neurons, repetitive cortical activation produced
      a short-term posttetanic potentiation (1-3 min). Subthreshold tetanic
      stimulation, which under control condition did not cause LTD, induced LTD when
      associated with membrane depolarization. Moreover, LTD was not expressed in cells
      in which the conditioning tetanus was coupled with hyperpolarization of the
      membrane. Bath application of aminophosphonovalerate (30-50 microM), an
      antagonist of NMDA receptors, did not affect the amplitude of the synaptic
      potentials and the expression of LTD. Striatal LTD was significantly reduced by
      the pretreatment of the slices with 30 microM 2-amino-3-phosphonopropionic acid,
      an antagonist of glutamate metabotropic receptors. LTD was not blocked by
      bicuculline (30 microM), a GABA(A) receptor antagonist. Scopolamine (3 microM),
      an antagonist of muscarinic receptors, induced a slight, but significant,
      increase of the amplitude of LTD. Both SCH 23390 (3 microM), an antagonist of D1
      dopamine (DA) receptors, and I-sulpiride (1 microM), an antagonist of D2 DA
      receptors, blocked LTD. LTD was also absent in slices obtained from rats in which
      the nigrostriatal DA system was lesioned by unilateral nigral injection of 6
      hydroxydopamine. In DA-depleted slices, LTD could be restored by applying
      exogenous DA (30 microM) before the conditioning tetanus. In DA-depleted slices,
      LTD could also be restored by coadministration of SKF 38393 (3-10 microM), a D1
      receptor agonist, and of LY 171555 (1-3 microM), a D2 receptor agonist.
      Application of a single class of DA receptor agonists failed to restore LTD.
      These data show that striatal LTD requires three main physiological and
      pharmacological conditions: (1) membrane depolarization and action potential
      discharge of the postsynaptic cell during the conditioning tetanus, (2)
      activation of glutamate metabotropic receptors, and (3) coactivation of D1 and D2
      DA receptors. Striatal LTD may alter the output signals from the striatum to the
      other structures of the basal ganglia. This form of synaptic plasticity can
      influence the striatal control of motor activity.

PMID- 1359032
TI  - Energy requirements of glutamatergic pathways in rabbit retina.
AB  - In vitro rabbit retina was used as an example of CNS tissue in experiments
      designed to measure the energy requirements associated with the activation of
      different types of glutamate receptors. Retinas were exposed to glutamate and to
      four analogs: kainate, 2-amino-4-phosphonobutyric acid (APB), 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), and 2-amino-5-phosphonovaleric acid (APV). The
      changes in O2 consumption and lactate production were determined using a recently
      developed experimental system that permitted simultaneous measurements of the
      rates at which O2 was removed from the medium and acid was added. The
      glutamatergic agents had relatively little effect on oxidative metabolism, but
      they caused large changes in glycolysis. Kainate increased retinal lactate
      production by 50%, whereas APB, CNQX, and APV reduced it by 23%, 19%, and 35%,
      respectively. Glutamate increased lactate production by 16% when administered
      after APB, but decreased it by 12% when administered after CNQX. The changes in
      energy metabolism coincided with changes in electrophysiological function. Since
      the energy metabolism of many retinal cells was presumably not much affected by
      the glutamatergic agents, the changes measured as a percent of total retinal
      glycolysis must have reflected considerably larger fractional changes in the
      cells most affected. From the response to inhibitors, it seems probable that even
      under resting conditions in darkness, activity in glutamatergic pathways is
      responsible for more than 50% of the glycolytically derived energy used by the
      cells involved. It also seems probable (particularly from the response to
      kainate) that under some circumstances the cells' energy metabolism and/or
      transport capability cannot meet the requirements imposed by glutamate-induced
      increases in function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359033
TI  - Identified postnatal mesolimbic dopamine neurons in culture: morphology and
      electrophysiology.
AB  - To examine the intrinsic properties of postnatal mesolimbic dopamine (DA)
      neurons, we dissociated the ventral tegmental area (VTA) from postnatal rats,
      enriched for DA neurons by microdissection or gradient purification, and grew the
      cells in culture. In these cultures, up to 50% of neurons were dopaminergic. DA
      neurons resembled their in vivo counterparts in soma shapes, and in showing two
      levels of tyrosine hydroxylase (TH) expression, axodendritic differentiation, two
      sizes of synaptic vesicles, nest-like synaptic arrangements with non-DA cells,
      and synaptic specializations. Electrophysiologically, however, they could not be
      distinguished from non-DA cells, which could be consistent with heterogeneity in
      cell properties. To examine a functional subset of VTA DA neurons, we
      retrogradely labeled VTA neurons projecting to the nucleus accumbens. These
      mesoaccumbens neurons were 86% TH positive, 56% cholecystokinin positive, and 0%
      neurotensin positive; they also displayed the soma shapes characteristic of DA
      neurons more generally and two levels of TH expression. Like their in vivo
      counterparts, mesoaccumbens cells generally fired single broad spikes that were
      triggered by slow depolarizations and had robust spike afterhyperpolarizations,
      low- and high-threshold Ca2+ spikes, rapid accommodation of firing, time
      dependent anomalous rectification, and hyperpolarizing autoreceptor responses.
      Strikingly, the expression of these active properties did not change with time in
      culture. Mesoaccumbens DA cells could be identified by a distinctive subset of
      properties that made up an electrophysiological signature; however, unlike their
      in vivo counterparts, they were less often spontaneously active and never fired
      in bursts. These results suggest that most DA cell properties are intrinsic to
      the cells, including a significant heterogeneity that is maintained in postnatal
      culture; their level and mode of activity, however, appear to require afferent
      input. Culturing identified postnatal VTA DA neurons now makes possible
      examination of the impact of their individual properties on synaptic function.

PMID- 1359034
TI  - The regional vulnerability to hypoglycemia-induced neurotoxicity in organotypic
      hippocampal culture: protection by early tetrodotoxin or delayed MK-801.
AB  - Profound hypoglycemia selectively damages CA1 and the dentate gyrus of the
      hippocampus. We have examined the time course of hippocampal neuronal injury in
      organotypic cultures following in vitro "hypoglycemia," using the fluorescent
      vital dye propidium iodide to observe directly the regional distribution of early
      neuronal membrane injury in living cultures. The in vivo hippocampal pattern of
      hypoglycemic injury was reproduced by a 2 hr exposure to glucose-free media,
      which resulted in simultaneous, selective propidium staining of CA1 and the
      dentate gyrus starting by 4 hr after exposure. After 24 hr of recovery, CA3
      remained spared. A similar pattern of propidium staining was produced by
      incubation of cultures for briefer periods in glucose-free medium containing 5 mM
      2-deoxyglucose (2-DG) to inhibit glycolysis. This "hypoglycemic" pattern and time
      course of neuronal injury was mimicked by 300 microM aspartate but not by
      glutamate. The NMDA receptor antagonists MK-801 and CPP, but not the relatively
      selective non-NMDA receptor antagonist 6-cyano-7-dinitroquinoxaline-2,3-dione,
      prevented the development of propidium staining. MK-801 protected against injury
      even if added to the recovery media 30 min after the insult, while TTX (10
      microM) protected only if added by the end of the exposure. The appearance of
      propidium staining after 4-6 hr of recovery was well correlated with histological
      observation of pyknotic neuronal nuclei in the injured regions. The
      characteristic hippocampal regional vulnerability of CA1 and the dentate gyrus to
      injury following profound hypoglycemia can be reproduced in organotypic
      hippocampal culture and appears to be mediated both by an early TTX-sensitive
      component and by a more prolonged period of toxic NMDA receptor activation,
      extending for at least 30 min into the recovery period.

PMID- 1359035
TI  - Pharmacological characterization of calcium currents and synaptic transmission
      between thalamic neurons in vitro.
AB  - We recorded from pairs of cultured, synaptically connected thalamic neurons.
      Evoked excitatory postsynaptic currents (EPSCs) reversed at +17 mV and were
      blocked reversibly by 1 mM kynurenic acid, a glutamate receptor antagonist. NMDA
      and non-NMDA receptors mediated excitatory post-synaptic responses, as shown by
      selective block of EPSC components with 50 microM (+/-)-2-amino-5
      phosphonopentanoic acid and 10 microM 6,7-dinitroquinoxaline-2,3-dione,
      respectively. Inhibitory postsynaptic responses were evoked less frequently and
      were blocked by the GABAA receptor antagonist (-)-bicuculline methochloride. The
      pharmacological profiles of whole-cell calcium currents and evoked EPSCs were
      compared. With 50 microM cadmium chloride (Cd), whole-cell low voltage-activated
      (LVA) calcium currents were reduced in amplitude and high voltage-activated (HVA)
      calcium currents and excitatory synaptic transmission were completely blocked.
      This suggests that the residual calcium influx through LVA channels into the
      presynaptic terminal does not suffice to trigger transmitter release. A
      saturating concentration of omega-conotoxin GVIA (omega-CgTx) (2.5 microM)
      blocked one-third of whole-cell HVA calcium currents and evoked EPSCs. The
      dihydropyridine nifedipine (50 microM) reversibly reduced whole-cell HVA calcium
      currents in a voltage-dependent manner but not excitatory synaptic transmission.
      Cd and omega-CgTx did not alter amplitude distributions of miniature EPSCs,
      demonstrating that the inhibition of synaptic transmission was due to block of
      presynaptic calcium channels. We conclude that excitatory glutamatergic
      transmission in thalamic neurons in vitro was mediated mainly by HVA calcium
      currents, which were insensitive to omega-CgTx and nifedipine.

PMID- 1359036
TI  - Inhibition of calcium channels in rat CA3 pyramidal neurons by a metabotropic
      glutamate receptor.
AB  - L-Glutamate rapidly and reversibly suppressed Ca channel current in freshly
      dissociated pyramidal neurons from the CA3 region of the rat hippocampus. L
      Glutamate inhibition of Ca channel current could be distinguished from activation
      of background conductance by appropriate ionic conditions and by distinct
      pharmacological profiles. Ca channel inhibition by glutamate was mimicked by
      quisqualate, ibotenate, racemict-ACPD and 1S,3R-ACPD but not by kainate, AMPA, L
      aspartate, NMDA, L-2-amino-4-phosphonobutyric acid, or 1R,3S-ACPD; 6-cyano-7
      nitroquinoxaline-2,3-dione did not inhibit the response. All agonists inhibited a
      similar fraction of high-voltage-activated Ca channel current, typically
      approximately 30%. Concentration-response relations for the agonists were
      consistent with mediation by a metabotropic glutamate receptor. The
      stereospecific agonist 1S,3R-ACPD was especially useful since it did not activate
      background conductances. The fraction of Ca channel current sensitive to 1S,3R
      ACPD was partially blocked by omega-conotoxin GVIA but was not sensitive to
      dihydropyridine antagonists or agonists. The suppression of Ca channels by 1S,3R
      ACPD became irreversible when cells were dialyzed with GTP-gamma-S. 1S,3R-ACPD
      suppressed Ca channel currents in outside-out membrane patches but not in cell
      attached patches when applied outside the patch. These results suggest that
      metabotropic glutamate receptors suppress the activity of N-type Ca channels in
      CA3 neurons by a mechanism involving G-proteins but not readily diffusible second
      messengers.

PMID- 1359039
TI  - Functional and structural properties of large arteries. Workshop of the
      International Society of Hypertension. Paris, France, 6-7 March 1992.

PMID- 1359037
TI  - 5' flanking sequences of the rat tyrosine hydroxylase gene target accurate tissue
      specific, developmental, and transsynaptic expression in transgenic mice.
AB  - Transgenic mice were generated in which sequences that flank the rat tyrosine
      hydroxylase (TH) gene were linked to the bacterial chloramphenicol acetyl
      transferase (CAT) gene. Mice bearing 4.8 kilobases (kb) of 5' flanking DNA
      exhibited correct tissue-specific expression in the CNS and periphery. Expression
      was more robust in the CNS than in the periphery, although CAT activity was
      clearly detected in sympathetic ganglia (superior cervical ganglia) and the
      adrenal, the two peripheral tissues that contain TH-positive cells. Within the
      brain, CAT expression was seen in all the expected areas containing TH-positive
      cell bodies, with little or no expression in other regions. In the olfactory
      bulb, which contains the majority of the CNS TH cells, developmental expression
      of CAT was quantifiable and was found to parallel the postnatal rise in
      endogenous TH, with both TH and CAT reaching adult levels by postnatal day 21.
      Since TH activity in the olfactory bulb requires afferent input, the dependence
      of CAT activity on transsynaptic input was also assayed in transgenic mice. Like
      the endogenous TH activity, CAT levels were also reduced by deafferentation, in
      parallel with loss in endogenous dopamine levels. While previous experiments
      demonstrated that shorter 5' flanking regions (2.5 kb and 3.5 kb of 5' upstream
      sequences of the human and mouse TH gene, respectively) failed to direct accurate
      tissue-specific expression, our data demonstrate that 4.8 kb of 5' flanking
      sequence of the rat TH gene contains sufficient regulatory information to mediate
      appropriate tissue-specific expression in all CNS and PNS tissues, as well as to
      mediate developmental and transsynaptic expression in the olfactory bulb.

PMID- 1359038
TI  - Fatty acid composition and fatty acid elongase and stearoyl-CoA desaturase
      activities in tissues of steers fed high oleate sunflower seed.
AB  - The effects of a high oleate sunflower seed diet on tissue composition and on
      fatty acid elongation and desaturation enzyme activities were investigated. Three
      Simmental calves were fed a standard corn-based diet (2.6% fat); three others
      were fed the corn-based diet containing 20% high oleate sunflower seed (10.4%
      fat). Blood samples and perianal adipose tissue samples were obtained at 7, 90
      and 180 d on trial. Samples of liver, longissimus dorsi muscle and intestinal
      mucosa were obtained at the termination of the experiment (195 d on trial).
      Plasma oleate was higher (P < 0.05) in the cattle fed the sunflower seed, and
      oleate, myristate (P < 0.05) and stearate (P < 0.06) were elevated in perianal
      adipose tissue in response to the greater lipid content of the dietary sunflower
      seed. Dietary sunflower seed decreased the concentration of stearate (P < 0.05)
      in liver. The high oleate diet significantly (P < 0.05) increased the activity of
      stearoyl-CoA desaturase activity in muscle, and numerical increases in desaturase
      activity were observed in liver, adipose and small intestine samples. Elongase
      activity was unaffected by diet. Because stearate is the primary fatty acid
      available for absorption in ruminants, elevated oleate in plasma and depressed
      stearate in liver of cattle fed sunflower seed may have reflected an adaptive
      response of stearoyl-CoA desaturase in their tissues.

PMID- 1359041
TI  - [The 93rd Congress of the Japanese Society of Otolaryngology. Nagoya, May 15-17,
      1992. Abstracts].

PMID- 1359040
TI  - Compliance changes in physiological and pathological states.
AB  - AIM: Although arterial compliance has been estimated by a variety of methods none
      of them can be directly validated because it is difficult to measure arterial
      volume. Moreover, because arterial pressure-volume relationships are non-linear,
      compliance is pressure-dependent. We have developed a method of estimating
      arterial compliance based on the Windkessel model of the arterial system that can
      account for the pressure-dependence of compliance. RESULTS: Compared to
      normotensive humans, compliance was decreased in hypertension and normalized with
      alpha-blockade, angiotensin converting enzyme inhibition and vasodilators, but
      not with beta-blockade. Compliance changes with aging, exercise and some diseases
      were determined. CONCLUSION: The decreased compliance seen in hypertension was
      due to an intrinsic change in the arterial wall, most likely due to increased
      smooth muscle tone.

PMID- 1359043
TI  - 9th International Congress on Care of the Terminally Ill. Montreal, Canada,
      October 31-November 4, 1992. Abstracts.

PMID- 1359042
TI  - Experience with a provocative test of calcitonin release as a prospective
      screening for preclinical medullary thyroid carcinoma in MEN type 2A family
      members.
AB  - We report our experience with a provocative test of calcitonin (CT) release using
      a combined stimulus of intravenous 10% CaCl2 solution and pentagastrin on 34
      normal adults (15 females: age 41 +/- 12.3 years and range 22-65 years; and 19
      males: age 43 +/- 9.1 years and range 23-60 years) and in 44 family members of
      three proven multiple endocrine neoplasia type 2A syndrome (MEN 2A) patients. A
      commercial radioimmunoassay was used to determine the serum CT levels. Peak CT
      levels were reached within 2 to 5 minutes after administration of the stimulus in
      all subjects tested. In the group of normal subjects there was no significant
      difference in the mean basal CT levels between males (54.8 +/- 21.7 pg/ml) and
      females (56.5 +/- 34.8 pg/ml), whilst the mean peak response values for males was
      146.3 +/- 120.6 pg/ml, which was significantly different from the mean value of
      females, namely 71.6 +/- 39.0 pg/ml. We did not find significant correlations
      between the basal CT level, peak CT response, and age. Of the 44 family members
      tested, 9 showed an exaggerated CT response to the combined stimulus and
      subsequently had a total thyroidectomy. Histological examination confirmed C-cell
      hyperplasia (CCH) in one and medullary thyroid carcinoma (MTC) in the other 8.
      Three of the 9 had high basal plasma CT levels. The 9 patients were retested
      postoperatively and all showed a flat response to the combined stimulus. Those
      family members with histological proof of MTC or CCH were screened for genetic
      linkage to the disease gene for MEN 2A using probe MCK2, and showed correlation
      in each instance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359044
TI  - Identical photosensitizing activities of a sulfonated aluminium phthalocyanine on
      human erythroleukemia cell lines susceptible or resistant to the cytotoxic
      activity of doxorubicin.
AB  - In this paper we report that a human erythroleukemia cell line made 100 times
      more resistant than the parental line to the cytostatic activity of doxorubicin
      and spontaneously 500-1000 times more resistant to the cytostatic activity of an
      unrelated drug, namely taxol, exhibits on the other hand unchanged susceptibility
      to the photosensitizing activity of a sulfonated phthalocyanine.

PMID- 1359046
TI  - Pseudoporphyria cutanea tarda: two case reports on children receiving peritoneal
      dialysis and erythropoietin therapy.
AB  - Pseudoporphyria cutanea tarda occurred in two children undergoing peritoneal
      dialysis and receiving erythropoietin therapy. The mechanism whereby
      erythropoietin might lead to photosensitization is unknown, but physicians should
      be aware of this possible association.

PMID- 1359045
TI  - Recurrent juvenile dermatomyositis and cutaneous necrotizing arteritis with
      molecular mimicry between streptococcal type 5 M protein and human skeletal
      myosin.
AB  - An adult patient had a syndrome associating the features of juvenile
      dermatomyositis and cutaneous polyarteritis nodosa that followed a cyclic course
      from childhood; recurrences were always associated with a rise of serum
      antistreptococcal antibodies. Regions of homology between streptococcal type 5 M
      protein and skeletal myosin were found. These findings suggest that streptococcal
      infection, possibly through a molecular mimicry mechanism, played a role in the
      pathogenesis of the disease in our patient.

PMID- 1359047
TI  - DNA testing for neurofibromatosis type 1.

PMID- 1359048
TI  - Impact of children's sickle cell history on nurse and physician ratings of pain
      and medication decisions.
AB  - The process of assessing and treating recurrent and unpredictable pain in
      children with sickle cell disease (SCD) is complex. A conceptual model is
      presented to aid in understanding the influence of mediating factors such as
      professional knowledge, attitudes and beliefs about pain, and learning history on
      the interpretation of objective data and resulting treatment decision. One aspect
      of this model, the effect of disease history on pain assessment and treatment
      decisions, is tested in an experimental study of SCD pain in children. Results
      suggest that nurses, but not pediatric residents, provide lower doses of narcotic
      analgesics to children with histories of frequent, as opposed to occasional,
      hospitalization for pain, although they do not differ in their ratings of the
      pain of children with these histories. Neither professional experience and
      training nor reported attitudes and beliefs about pain in children are related to
      this pattern of decision making. Results are discussed in terms of the aversive
      impact of repeated exposure to a noxious stimulus (pain behaviors) on caregiver
      interpretation of pain cues.

PMID- 1359049
TI  - Proceedings of the 13th Symposium on the Interaction between Biological Membranes
      and Drugs. Tokyo, November 15-16, 1991.

PMID- 1359050
TI  - Quantitative skin blanching assay of corticosteroid creams using tristimulus
      colour analysis.
AB  - The potencies of four proprietary corticosteroid creams were ranked using
      blanching measured by a tristimulus colour analyser as an index. Intra-subject
      variation was measured in a trial using a single subject while in a second study
      inter-subject variation was quantified using six volunteers. Discriminative
      parameters were derived from the extended multiple-point chromaticity coordinates
      L* and a* recorded after application of the steroid creams under occlusion.
      Analysis of variance of the data using the linear regression model was followed
      by Tukey's multiple comparison tests. Ranking of the creams using parameters of
      the pharmacodynamic response corresponded with the generally accepted rank order
      of the potencies of the corticosteroid creams. It is proposed that this multiple
      point skin blanching assay of topical corticosteroids using an internationally
      accepted clear measurement standard and the subsequent data analysis be adopted
      as a standard protocol.

PMID- 1359052
TI  - Effect of freezing on iontophoretic transport through hairless rat skin.
AB  - The influence of frozen storage of hairless rat skin on the constant-current
      iontophoretic transport of a model weak acid, salicylic acid, was examined.
      Nearly a threefold increase was observed in the steady-state flux of salicylic
      acid through previously frozen skin (217.1 nmol h-1 cm-2) when compared with
      fresh, excised skin (72.3 nmol h-1 cm-2). The iontophoretic permeability of skin
      to salicylic acid was also found to be dependent upon the length of time skin
      samples remained in the frozen state. Differential scanning calorimetry studies
      revealed distinct differences in the thermograms for fresh and frozen skin. These
      results suggest that storage of skin samples in the frozen state may contribute
      to physical or chemical changes in skin structure.

PMID- 1359051
TI  - The pharmacology of a novel topical retinoid, BMY 30123: comparison with
      tretinoin.
AB  - Preclinical studies pertaining to the pharmacology and toxicology of BMY 30123 (4
      acetamidophenyl retinoate) are reported. BMY 30123 is a novel compound which has
      topical retinoid activity. This compound exhibits lower toxicity, both local and
      systemic, than other clinically used topical retinoids such as tretinoin (all
      trans retinoic acid) in animal models. BMY 30123 is effective in a number of
      retinoid sensitive skin models including the rhino mouse utriculi reduction
      assay, the mouse epidermal hyperplasia model and in the suppression of DNA
      synthesis in mouse skin stimulated with phorbol ester. BMY 30123 was equipotent
      with tretinoin in these topical models. In the rhino mouse model the ED30 values
      for BMY 30123 and tretinoin were 0.037 and 0.015 mM, respectively. In addition,
      BMY 30123 was active in the UVB-induced photodamaged mouse model, another
      retinoid sensitive model. One of the problems associated with topically applied
      tretinoin is local irritation. Therefore, for topical therapy to be optimal, it
      is important to reduce or minimize local irritation. Repeated applications of BMY
      30123 to rabbit skin resulted in low skin irritation. The first perceptible signs
      of skin irritation produced by BMY 30123 occurred at a dose 10 times higher than
      that observed for tretinoin. BMY 30123 also exhibits low retinoid activity after
      oral or i.p. administration in mice and produced no signs of hypervitaminosis A
      related toxicity at twenty times the no effect dose of tretinoin. Because
      retinoids are effective modulators of epidermal growth and differentiation, this
      compound should be useful for the treatment of cutaneous disorders that exhibit
      altered epidermal differentiation such as acne, psoriasis, ichthyosis and
      epithelial tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359053
TI  - Parthenolide content and bioactivity of feverfew (Tanacetum parthenium (L.)
      Schultz-Bip.). Estimation of commercial and authenticated feverfew products.
AB  - Three physicochemical methods (HPLC, NMR spectroscopy, and HPLC of a derivative)
      have been used to measure parthenolide in authenticated Tanacetum parthenium
      (feverfew) and in several commercial purported feverfew products. A bioassay
      based on inhibition of the secretory activity of blood platelets by extracts of
      feverfew in comparison with parthenolide was also used. Similar results were
      obtained for all three physicochemical assays and also for the bioassay. Thus
      different methodologies yield consistent values for parthenolide content of
      feverfew preparations. Parthenolide appears to be mainly responsible for the
      antisecretory effects of extracts of feverfew. Authenticated Tanacetum parthenium
      grown in the UK contained a high level of parthenolide in leaves, flowering tops
      and seeds but a low level in stalks and roots. The level of parthenolide in
      powdered leaf material fell during storage. The purported feverfew products
      varied widely in their parthenolide content and in some products parthenolide was
      not detected. Possible reasons for the variation in parthenolide content are
      discussed. Since therapeutic efficacy has only been demonstrated for preparations
      of feverfew that contain parthenolide, it is suggested that manufacturers of
      feverfew products should use measurements of parthenolide as a means of
      standardization and quality control.

PMID- 1359054
TI  - Effects of the mucoadhesive polymer polycarbophil on the intestinal absorption of
      a peptide drug in the rat.
AB  - The absorption across rat intestinal tissue of the model peptide drug 9
      desglycinamide, 8-arginine vasopressin from bioadhesive formulations was studied
      in-vitro, in a chronically isolated internal loop in-situ and after intraduodenal
      administration in-vivo. A controlled-release bioadhesive drug delivery system was
      tested, consisting of microspheres of poly(2-hydroxyethyl methacrylate) with a
      mucoadhesive Polycarbophil-coating, as well as fast-release formulation
      consisting of an aqueous solution of the peptide in a suspension of Polycarbophil
      particles. Using the controlled-release system, a slight improvement of peptide
      absorption was found in-vitro in comparison with a non-adhesive control system,
      but not in-situ or in-vivo. In contrast, bioavailability was significantly
      increased in all three models from the Polycarbophil suspension in comparison
      with a solution of the drug in saline. The effect appeared to be dose-dependent,
      indicative of intrinsic penetration-enhancing properties of the mucoadhesive
      polymer. A prolongation of the absorption phase in-vitro and in the chronically
      isolated loop in-situ suggested that the polymer was able to protect the peptide
      from proteolytic degradation. This could be confirmed by degradation studies in
      vitro. The duration of the penetration enhancing/enzyme inhibiting effect was
      diminished with increasing complexity of the test model, in the same way as was
      previously found for the bioadhesive effect. This interrelationship suggests that
      the observed improvement in peptide absorption and the mucoadhesive properties of
      this polymer are associated. The development of a fast-release oral dosage form
      for peptide drugs on the basis of Polycarbophil appears to be possible.

PMID- 1359055
TI  - Dose-dependent inhibition in plasma protein binding of valproic acid during
      continued treatment in guinea-pigs.
AB  - Plasma protein binding of valproic acid over a wide range of steady-state plasma
      concentration (11.3 +/- 2.6-1303.0 +/- 122.9 micrograms mL-1: s.e.m., n = 5) in
      guinea-pigs has been studied. Valproic acid was given by intravenous constant
      infusion. At steady-state the plasma protein binding of valproic acid was
      analysed. Nonlinear binding was observed. Unbound fraction (fu) of valproic acid
      increased from 25 to 95% with the increase of steady-state plasma concentration
      (Css). The plasma protein-bound drug concentration (Cb) of valproic acid
      increased initially with Css but decreased after the Css exceeded 345.0
      micrograms mL-1, where the Cb was 152.5 +/- 26.8 micrograms mL-1. At a Css of
      1303.3 +/- 122.9 micrograms mL-1 the Cb was significantly (P less than 0.05)
      decreased to 72.8 +/- 20.2 micrograms mL-1. Binding characteristics of valproic
      acid in-vitro were studied using drug-free guinea-pig plasma with added valproic
      acid (10-1000 micrograms mL-1). The binding behaviour was also nonlinear in
      vitro. The fu increased from 14 to 79% with the increase of valproate
      concentrations. No decrease in Cb was observed throughout the range. The study
      demonstrated that binding characteristics of valproic acid in-vivo and in-vitro
      are not parallel. The results suggest that valproic acid may produce or induce
      plasma protein binding competitors; metabolites of valproic acid may be
      implicated.

PMID- 1359056
TI  - Pharmacokinetics of moclobemide in male, virgin female, pregnant and nursing
      rats.
AB  - The disposition of moclobemide, a reversible inhibitor of monoamine oxidase
      isoenzyme A was studied in male, virgin female, pregnant and nursing rats. The
      average clearance in control rats (male and female) was 36 mL min-1 kg-1, the
      initial volume of distribution 1.4 L kg-1, the volume of distribution at steady
      state 2.3 L kg-1 and the terminal half-life 59 min. The blood-to-plasma
      concentration ratio of moclobemide was 0.84 giving rise to an average blood
      clearance of 30 mL min-1 kg-1. The clearance values in rats were higher than in
      man but as a fraction of hepatic blood flow were similar (36 vs 45%). The volume
      of distribution at steady state was approximately twice as high as in man while
      the half-life was similar. Pregnant and nursing rats showed no statistically
      significant differences in their disposition parameters for moclobemide compared
      with virgin female rats. Nursing rats had statistically significantly lower
      concentrations of the moclobemide N-oxide metabolite than did pregnant and
      control rats. Generally lower concentrations of the lactam metabolite were also
      found in this group although the differences did not reach statistical
      significance. Moclobemide as well as the N-oxide and lactam metabolites were
      found in the amniotic fluid suggesting that moclobemide is capable of crossing
      the placental barrier.

PMID- 1359057
TI  - In-vitro evaluation of 5-lipoxygenase and cyclo-oxygenase inhibitors using bovine
      neutrophils and platelets and HPLC.
AB  - Inhibition of 5-lipoxygenase has been determined by monitoring the formation of
      leukotriene B4 and 5-hydroxyeicosatetraenoic acid in bovine polymorphonuclear
      leucocytes. For evaluating the inhibition of cyclo-oxygenase two different test
      systems are presented: the first uses 12-hydroxyheptadecatrienoic acid produced
      by bovine platelets as an indicator of the cyclo-oxygenase activity; the second
      test system monitors the prostaglandin E2 formation by bovine platelets. All
      arachidonic acid metabolites are quantified by reverse-phase HPLC with UV
      detection.

PMID- 1359058
TI  - Vasorelaxant effect of trapidil on human basilar artery.
AB  - We have investigated the vasorelaxant effect of trapidil on human isolated
      basilar artery. Trapidil (10(-5)-10(-4) M) dose-dependently caused relaxation in
      vascular strips with or without endothelium, with no significant difference
      between the two types of strips. The relaxation responses were not inhibited by
      atropine, propranolol or methylene blue. Trapidil increased the concentration of
      6-keto-PGF1 alpha, a prostacyclin degradation product, released from an artery
      ring in the incubation medium, but trapidil-induced relaxation was not inhibited
      by indomethacin. Pretreatment of vascular strips with 10(-5) M trapidil increased
      the relaxation responses to forskolin and dibutyryladenosine cyclic monophosphate
      but not to sodium nitroprusside or 8-bromoguanosine cyclic monophosphate.
      Trapidil induced a significant increase in the cAMP concentration but not in the
      cGMP concentration in artery strips. These results suggest that the relaxation
      response to trapidil is not caused by prostacyclin release or an increase in cGMP
      in the smooth muscle, but possibly by an increase in the cAMP levels, probably
      via an inhibitory effect on cAMP phosphodiesterase.

PMID- 1359059
TI  - A comparative study on desipramine pharmacokinetics in the rat brain after
      administration of desipramine or imipramine.
AB  - Chronic intraperitoneal administration of desipramine led to an extensive
      cumulation of the drug in brain and blood compared with that after a single dose
      treatment, while chronic treatment with desipramine by the oral route produced a
      brain concentration comparable with its level after a single oral dose.
      Comparison of the present results with the corresponding data of published
      imipramine pharmacokinetics indicated that the cumulation of desipramine in the
      rat brain was nearly the same when rats received desipramine or imipramine twice
      a day for two weeks at a dose of 10 mg kg-1 orally, or imipramine, twice a day
      for two weeks at a dose of 10 mg kg-1 intraperitoneally. It is suggested that
      these three experimental paradigms may be used as models for differentiation of
      the pharmacological effects of imipramine and desipramine in-vivo.

PMID- 1359060
TI  - Failure of verapamil and diltiazem to attenuate the pressor response to
      hypothalamic stimulation: a possible mechanism.
AB  - The effects of verapamil or diltiazem on pressor responses to posterior
      hypothalamic stimulation, injected noradrenaline or tyramine were studied in
      urethane-anaesthetized normotensive, deoxycorticosterone acetate (DOCA), renal
      and spontaneously hypertensive rats at the early and established phases of
      hypertension. Pressor responses to the pressor stimuli were significantly
      enhanced in the early and established phases of hypertension when compared with
      the normotensives. While the magnitude of pressor responses in the established
      phase of renal or spontaneously hypertensive rats was significantly higher (P
      less than 0.05) than the corresponding value in the early phase, in contrast, the
      pressor response in the early phase of DOCA hypertension was significantly higher
      than that of the established phase. Verapamil or diltiazem significantly (P less
      than 0.005) inhibited pressor responses to injected noradrenaline or tyramine in
      all groups of rats but not that to hypothalamic stimulation, irrespective of the
      stage of hypertension. When the probable mechanism of the hypothalamic pressor
      response's resistance to the calcium antagonists was studied in-vitro, ATP
      significantly (P less than 0.005) inhibited the relaxant effect of the calcium
      antagonists in the rat aortic strips. Our data indicate that verapamil or
      diltiazem is ineffective in inhibiting the pressor response to posterior
      hypothalamic stimulation. The probable mechanism of the resistance and the
      clinical implication of the findings are discussed.

PMID- 1359061
TI  - Bupivacaine kinetic changes during the oestrous cycle in rats.

PMID- 1359062
TI  - Use of prostaglandin E1 (lipo-PGE1) to treat Raynaud's phenomenon associated with
      connective tissue disease: thermographic and subjective assessment.
AB  - Four patients with connective tissue disease who had been suffering from severe
      Raynaud's phenomenon were treated with an intravenous infusion of prostaglandin
      E1 (PGE1) and its effectiveness was assessed by thermography and a questionnaire
      approach. PGE1 in a lipid microsphere formulation (lipo-PGE1) produced a
      significantly greater increase in lesional skin temperature compared with
      treatment with PGE1 clathrated in alpha-cyclodextrin 12 months previously in the
      same group of patients. These results were supported by the subjective assessment
      obtained from the patients by questionnaire.

PMID- 1359063
TI  - Iontophoretic permeation of sodium cromoglycate through synthetic membrane and
      excised hairless mouse skin.
AB  - The iontophoretic transport properties of sodium cromoglycate were characterized
      using a synthetic membrane and excised hairless mouse skin. The permeation rate
      of sodium cromoglycate through the synthetic membrane was found to be linearly
      dependent on the density of electrical current applied. Passive diffusion through
      the excised hairless mouse skin was not demonstrated for sodium cromoglycate;
      however, under iontophoresis, an appreciable permeation was exhibited by the drug
      through the animal skin, which was also found to be a function of the electrical
      current density.

PMID- 1359064
TI  - Elimination of non-reactive and weakly reactive human alpha 1-acid glycoprotein
      after induction of the acute phase response in rats.
AB  - The disposition of concanavalin A (Con A)-non-reactive and Con A-reactive human
      alpha 1-acid glycoprotein (AAG) was studied in normal male rats and in acute
      phase response-activated male rats. Activation of the acute phase response was
      made using a subcutaneous administration of ethynyloestradiol in sesame oil. This
      technique increased the endogenous AAG concentration 7-fold. In control rats the
      two forms of human AAG showed identical kinetics with an average clearance of 5.4
      mL h-1 kg-1, terminal half-life of 13.5 h and a volume of distribution (steady
      state) of 91 mL kg-1. In the acute phase response-activated animals, both the
      clearance and volume of distribution were larger: the average clearance of the
      Con A-non-reactive AAG was 10.2 mL h-1 kg-1, the volume of distribution (steady
      state) 152 mL kg-1 and the terminal half-life 11.7 h. The Con A-reactive AAG had
      a clearance of 14.7 mL h-1 kg-1, a volume of distribution (steady state) of 262
      mL kg-1 and a half-life of 15.8 h. The results indicate that not only does
      activation of the acute phase response alter the kinetics of AAG but that the
      change is different for the different types of AAG.

PMID- 1359065
TI  - Ageing influences haloperidol-induced changes in the permeability of the blood
      brain barrier in the rat.
AB  - The effect of the dopaminergic antagonist haloperidol on the permeability of the
      blood-brain barrier (BBB) to [14C]alpha-aminoisobutyric acid was studied in 10-12
      and 28-30-week old rats. Following the intraperitoneal injection of haloperidol
      (1 mg kg-1), an increase in the permeability of the BBB, with respect to younger
      animals, was observed within the occipital cortex, striatum, hippocampus and
      hypothalamus in the older rats. No correlation was found between haloperidol
      induced changes and age-related differences in the permeability of the BBB. Such
      age-associated increase in the vulnerability of the BBB when challenged with
      haloperidol might be related to a deterioration of the dopaminergic control of
      cerebrovascular permeability.

PMID- 1359066
TI  - Similar effects of nifedipine and hydralazine on anaesthesia and hypermotility
      induced by pentobarbitone in mice.
AB  - Nifedipine, a dihydropyridine calcium channel blocker, and hydralazine, a non
      calcium channel antagonist vasodilatator, enhanced pentobarbitone-induced
      sleeping time and reversed locomotor hyperactivity induced by a subhypnotic dose
      of the barbiturate in mice. The similarity of the behavioural effects, exerted by
      nifedipine and hydralazine, suggest that haemodynamic factors may play an
      important role in the interaction of calcium channel antagonists with
      barbiturates.

PMID- 1359067
TI  - Anti-inflammatory activity of oleanolic acid in rats and mice.
AB  - Oleanolic acid displayed anti-inflammatory activity in carrageenan and dextran
      induced oedema in rats. It elicited marked anti-arthritic action in adjuvant
      induced polyarthritis in rats and mice and in formaldehyde-induced arthritis in
      rats. Oleanolic acid checked the inflammation-induced increased serum
      transaminase levels. It reduced exudate volume and inhibited leucocyte
      infiltration in carrageenan-induced pleurisy in rats. It is devoid of any
      analgesic, antipyretic or ulcerogenic action. Oleanolic acid did not affect the
      parturition time in pregnant rats or castor oil-induced diarrhoea in rats. Oral
      LD50 was found to be greater than 2 g kg-1 in mice and rats.

PMID- 1359068
TI  - Estimation of elastic recovery, work of decompression and Young's modulus using a
      rotary tablet press.
AB  - Capping and lamination occur when the bonds within a tablet cannot withstand the
      elastic recovery during decompression. To estimate tablet recovery, it is
      necessary to subtract the machine recovery from the total recovery during
      decompression. A direct relationship between the force and machine deformation is
      applied in a novel fashion to calculate in-die tablet recovery on a Manesty
      Betapress and to estimate the Young's modulus, E, of various solids from the
      recovery data. The E values of about twenty-five pharmaceutical solids were found
      to be in reasonable agreement with literature values. This procedure allows in
      process analysis of tablet recovery and gives E without the use of specialized
      equipment.

PMID- 1359069
TI  - Interaction and aggregation of sodium aurothiomalate and poly L-lysine.
AB  - This report describes the interaction and aggregation of sodium aurothiomalate
      with polylysine, a potentially useful property, both as a model for drug-protein
      interaction and as a means of reversibly immobilizing sodium aurothiomalate.
      Sodium aurothiomalate formed stable precipitates with polylysine at neutral pH,
      ionic strengths below 1M NaCl, and optimally, at sodium aurothiomalate to lysine
      ratios of less than one. The interaction could be demonstrated both by
      precipitation (which was sensitive to the size of polylysine polymer) and by
      using polylysine immobilized to Sepharose. Precipitation could be inhibited by
      addition of the organic thiomalate moiety alone. These findings indicate that the
      interaction of sodium aurothiomalate with polylysine is by electrostatic bonding
      of the thiomalate (mercaptosuccinate) moiety and the epsilon-amino groups of
      lysine residues. At suitable molar ratios this will link together many polylysine
      chains leading to precipitation. This represents a potentially valuable
      interaction for immobilization of the drug and in the formation of conjugates.

PMID- 1359070
TI  - Doxorubicin-loaded casein microspheres: protein nature of drug incorporation.
AB  - We have studied incorporation of [14C]doxorubicin within protease-sensitive
      casein microspheres both by 14C-activity, measuring total drug, and HPLC,
      measuring free drug only. It was found that total drug content (27.7 micrograms
      mg-1) exceeded free drug content (3.2 micrograms mg-1) suggesting that the major
      portion of doxorubicin was incorporated via a covalent linkage to matrix protein.
      In-vivo drug disposition and activity studies suggested that this fraction of
      doxorubicin was the major species within tumour tissue (total vs free: 5 min,
      14.3 micrograms g-1 vs 0.7 micrograms g-1; 24 h, 11.7 micrograms g-1 vs 1.1
      micrograms g-1; 48 h, 11.2 micrograms g-1 vs 1.2 micrograms g-1; 72 h, 10.0
      micrograms g-1 vs 0.8 micrograms g-1), did not exhibit a 'burst' effect, was
      slowly cleared (30% loss over 3 days), and was equiactive (growth delay = 12
      days) compared with drug in solution (growth delay = 10 days). This work clearly
      implicates in-vivo microsphere matrix biodegradation in drug release and
      subsequent disposition and activity.

PMID- 1359072
TI  - Effect of theophylline on the intestinal clearance of drugs in rats.
AB  - Intestinal exsorption of salicylic acid, urea and quinidine was measured during
      the perfusion of the rat intestinal lumen with Tyrode solution. The intestinal
      clearance (CLi) of the three compounds was measured by dividing the rate of
      appearance in the intestinal luminal perfusate by the plasma concentration of the
      compound. Co-administration of theophylline (0.2 mg h-1) with the test agents
      increased the CLi of salicylic acid, did not alter the CLi of urea, but decreased
      the CLi of quinidine. The effect of theophylline on the CLi of quinidine was
      enhanced with increasing dose. Theophylline was found to increase microclimate-pH
      at the intestinal surface, but the magnitude of delta pH alone could not explain
      the effect of theophylline on the CLi of quinidine. The data, together with
      previous observations, suggest that the intestinal exsorption of drugs was
      affected by the microclimate pH and by the unstirred water layer. Theophylline
      affects CLi of salicylic acid and quinidine partly by increasing the microclimate
      pH of the intestine. Theophylline may also affect quinidine CLi by inhibiting the
      carrier-mediated pathway.

PMID- 1359071
TI  - Anti-ulcer activity of a slow-release zinc complex, zinc monoglycerolate
      (Glyzinc).
AB  - A slow-release zinc complex, zinc monoglycerolate (ZMG) was examined for its
      potential gastroprotective activity in various gastric ulcer models. These models
      comprised (a) oral or parenteral non-steroidal anti-inflammatory drugs (NSAIDs)
      given to rats whose gastrointestinal mucosa was pre-sensitized by prior
      development of arthritis, oleyl alcohol-induced inflammation and cold exposure,
      (b) oral ethanol (12.5-100%) with and without added 4% HCl, (c) intraperitoneal
      reserpine (5 mg kg-1) in arthritic and normal rats and in normal mice, (d) oral
      NSAIDs given to mice in which acid and pepsin production was stimulated by co
      administration of intraperitoneal bethanechol chloride (5 mg kg-1) to enhance
      ulcer development, and (e) NSAIDs given to carrageenan-inflamed rats to determine
      effects of ZMG on paw inflammation. In these models, ZMG given orally was
      effective in preventing development of gastric lesions, except with propionic
      acid NSAIDs; the effective doses being apparently dependent on the severity of
      the mucosal injury. In many of the models ZMG was superior to zinc sulphate and
      other zinc salts or metal ion complexes investigated but was slightly more
      effective or equipotent compared with zinc acexamate. ZMG did not impair the anti
      oedemic effects of NSAIDs. ZMG is thus an effective agent in preventing ulcer
      development in a wide range of model systems and may be more effective than zinc
      salts because of the controlled slow-release of zinc from the complex.

PMID- 1359073
TI  - Characteristics of procarbazine as an inhibitor in-vitro of rat semicarbazide
      sensitive amine oxidase.
AB  - Procarbazine (N-isopropyl-alpha-(2-methyl hydrazino)-p-toluamide hydrochloride)
      inhibited more powerfully the deamination of benzylamine by semicarbazide
      sensitive amine oxidase (SSAO) of rat brown adipose tissue than the deamination
      of 5-hydroxytryptamine and benzylamine by rat liver monoamine oxidase-A or -B
      activities, respectively. Inhibition of SSAO, but not monoamine oxidase, was time
      dependent. Use of metabolic inhibitors, and an enzyme dilution technique,
      suggested that any conversion of procarbazine to an active species must be as a
      result of the action of SSAO itself and not of any other enzyme. The non
      competitive kinetics and the time-dependence of inhibition were indicative of a
      suicide interaction between procarbazine and SSAO. The slow reversal of
      inhibition by dialysis was evidence in favour of the involvement of tight
      binding, rather than covalent bonding. High concentrations of benzylamine
      afforded the enzyme significant protection from the action of procarbazine,
      indicating that the interaction is at or near the active site. If the properties
      of procarbazine, evident in in-vitro studies, are retained in-vivo, these data
      suggest that procarbazine might be suitable for the examination of SSAO
      activities, both in-vivo and ex-vivo.

PMID- 1359074
TI  - Effects in-vitro of procarbazine metabolites on some amine oxidase activities in
      the rat.
AB  - The effects were examined of four metabolites of the anticancer agent,
      procarbazine (N-isopropyl-alpha-(2-methyl hydrazino)-p-toluamide hydrochloride)
      on semicarbazide-sensitive amine oxidase (SSAO) and monoamine oxidase-A and -B
      (MAO-A and -B) activities in rat brown adipose tissue and liver homogenates,
      respectively. Azoprocarbazine (AZO) and monomethylhydrazine (MMH) inhibited
      selectively the deamination of benzylamine by SSAO, when compared with their
      effects on MAO activities. The IC50 values against SSAO, of 32.7 nM (AZO) and 7.0
      nM (MMH), were more than three orders of magnitude lower than those exhibited
      against MAO. Neither isomer of azoxyprocarbazine was an effective inhibitor of
      rat amine oxidase activities. The inhibition of SSAO by AZO was reversed very
      slowly by dialysis, in contrast to results seen for MMH. The non-competitive
      kinetics of MMH and the ability of B24, a rapidly reversible SSAO inhibitor, to
      protect SSAO against inhibition by MMH are consistent with the view that this
      compound binds to the enzyme cofactor at, or near, the active site.

PMID- 1359076
TI  - In-vitro assessment of a matrix system of levobunolol.
AB  - In order to study the feasibility of systemic delivery of levobunolol
      transdermally, a matrix-type delivery system was fabricated using a silicone
      elastomer. The relationship between loading dose and skin permeation rate was
      evaluated in-vitro using hairless mouse skin mounted on the stirred receptor
      compartment of the Keshary-Chien glass diffusion cell maintained at 37 degrees C.
      The concentration of levobunolol in the receptor compartment was determined by
      HPLC. A similar study without using the skin was carried out to determine the
      effect of loading dose on the release of levobunolol from discs. It was observed
      that the release of drug from disc followed a matrix-diffusion controlled (Q) vs
      square root of time relationship at different loading doses. In contrast, the
      results of skin permeation of levobunolol from transdermal discs containing
      different loading doses showed a linear Q vs time relationship indicating a
      constant zero order skin permeation rate at each loading dose. Skin permeation of
      levobunolol appeared to reach a plateau at a 5% (w/w) loading dose in the disc
      indicating the attainment of equilibrium concentration of levobunolol in the
      skin.

PMID- 1359075
TI  - Effects of calcium antagonists on rat normal and skinned fundus.
AB  - Calcium chloride (CaCl2) (0.1-25 mM, in K(+)-depolarized tissue), KCl (10-112 mM)
      and acetylcholine (1 x 10(-9) M-1 mM) produced concentration-dependent
      contractions of rat isolated fundus. Verapamil (0.01-100 microM), cinnarizine (1
      100 microM), trifluoperazine (10-500 microM) and dantrolene (50-250 microM) each
      produced a concentration-related rightward and downward shift of the log
      concentration-effect curve for CaCl2. The rank order of potencies of these
      antagonists, measured as the IC50 against Ca2+ (25 mM)-induced contraction of
      depolarized fundus, was verapamil (2.5 microM) greater than cinnarizine (8.7
      microM) greater than trifluoperazine (85.1 microM) greater than dantrolene
      (greater than 250 microM). Cinnarizine (0.5 mM) and trifluoperazine (0.5 mM), but
      neither verapamil nor dantrolene depressed Ca2+ (20 microM)-evoked contraction of
      rat skinned fundus preparations. In intact preparations of rat fundus, verapamil
      had greater inhibitory effects on contractions produced by KCl than against those
      elicited by acetylcholine while trifluoperazine depressed to the same extent the
      responses to these two spasmogens. Dantrolene was without effect on contractions
      elicited by KCl or acetylcholine. Cinnarizine inhibited acetylcholine-induced
      responses but enhanced contractions to KCl. Augmentation of KCl-induced responses
      by cinnarizine is resistant to verapamil (1 microM). This enhancing effect of
      cinnarizine was not observed for KCl-induced contraction of guinea-pig fundus or
      rat gastro-oesophageal sphincter. In the rat fundus, cinnarizine (1-100 microM)
      produced an additional and concentration-related contraction when added on the
      plateau contraction to KCl (100 mM). The enhancing effect and the direct
      contraction produced by cinnarizine are at least partly dependent on
      extracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359077
TI  - Compatibility study between acetylcysteine and some commonly used tablet
      excipients.
AB  - Differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy
      (FT-IR), HPLC and TLC were used to investigate the interactions between the
      mucolytic drug acetylcysteine and a number of commonly used tablet and capsule
      excipients. Acetylcysteine was found to be compatible with microcrystalline
      cellulose (Avicel PH 101), sodium carboxymethylcellulose, amorphous silicon
      dioxide (Aerosil), PVP, cross-linked PVP (Polyplasdone XL), corn starch,
      saccharose and magnesium stearate. Acetylcysteine thermal stability (onset
      degradation temperature) was decreased in mixtures with corn starch, magnesium
      stearate, saccharose and lactose. Interactions of acetylcysteine with lactose,
      PEG 4000 and 6000, glycine, adipic acid and saccharin sodium were found using DSC
      and studied in detail with FT-IR, HPLC and TLC. The results suggest that
      acetylcysteine in mixtures with PEG 4000, glycine or saccharin sodium is degraded
      during storage at conditions of high temperature and humidity.

PMID- 1359079
TI  - MK-801 antagonizes the lethal action of centrally and peripherally administered
      cypermethrin in mice and rats.
AB  - The present study investigated the effect of MK-801, an N-methyl-D-aspartate
      antagonist, on the convulsant lethal action of cypermethrin administered
      centrally or peripherally. Cypermethrin produced severe convulsions and death in
      a dose-dependent manner. MK-801 (0.5, 1 and 2 mg kg-1, intraperitoneally)
      significantly increased the onset time of convulsions and decreased the mortality
      in the peripherally treated cypermethrin group. MK-801 (1.0 and 2.0 mg kg-1)
      attenuated the convulsant action of cypermethrin (50 micrograms,
      intracerebroventricularly) significantly. Survival rate was also increased
      significantly. However, MK-801 (0.5 mg kg-1) did not produce any significant
      protective effect against centrally administered cypermethrin. These results
      suggest excitatory amino acids to be a target for pyrethroid-induced
      neurotoxicity.

PMID- 1359080
TI  - Supersensitivity to morphine after chronic sympathetic denervation in guinea-pig
      colon.
AB  - The possible role of opioid systems in the adaptive changes which follow chronic
      sympathetic denervation in the guinea-pig colon has been studied by comparing the
      effects of the opioid agonist morphine in control animals and after chronic
      sympathetic denervation. Supersensitivity to the inhibitory effects of morphine
      on the peristaltic reflex was observed after chronic sympathetic denervation,
      while the potency against acetylcholine release was unmodified. Our results
      suggest that a modification of the opioid system occurs after sympathetic
      denervation in the guinea-pig colon. Supersensitivity to endogenous opioids at a
      site different from that regulating acetylcholine release could account for the
      counter-regulation of intestinal motility after chronic sympathetic denervation.

PMID- 1359078
TI  - Polyethylene glycol: its adverse gastric effects in rats.
AB  - The effects of polyethylene glycol (PEG) on gastric function and on lesion
      formation, evoked by topical applications of absolute ethanol to an ex-vivo
      stomach chamber preparation have been examined. Parenteral injection (i.p. or
      s.c.) of PEG with different molecular weights (PEG 300, 400 or 4000), dose
      dependently reduced the gastric mucosal blood flow and volume of gastric
      secretion; these effects were greater in rats given PEG by the i.p. route, which
      also lowered acid output. Topical application of 1.5 mL absolute ethanol produced
      severe gastric mucosal injury, which was exacerbated by PEG; this lesion
      aggravating effect was higher in the i.p.-injected groups. These findings
      indicate that when PEG is given by injection, it can adversely affect gastric
      function and increase the damaging action of alcohol. It is suggested that the
      use of PEG as a vehicle for injection should be re-assessed.

PMID- 1359081
TI  - Sulphasalazine fails to prevent development of mucosal ulceration and 5
      lipoxygenase activity in guinea-pigs with chronic inflammatory bowel disease
      induced by combined bacterial immunization and oral carrageenin.
AB  - A model of inflammatory bowel disease in guinea-pigs involving a 14 day initial
      treatment with formalin-killed Bacteroides vulgatus subcutaneously and oral
      carrageenin plus live B. vulgatus for 10 days was used to determine the effects
      of sulphasalazine 100 mg kg-1 day-1 b.i.d., p.o. given for 4, 7 and 10 days after
      cessation of the bacterial/carrageenin treatment on the morphological and
      histological states of the established disease and on the production of the
      principal 5-lipoxygenase products, 5-hydroxyeicosatetraenoic acid and leukotriene
      B4. The drug treatment did not cause any significant changes in this established
      disease as measured by these parameters.

PMID- 1359082
TI  - Influence of changes in protein binding on the central activity of
      antidepressants.
AB  - The central effect (expressed as analgesic response), protein binding and brain
      uptake of mianserin were measured in mice receiving drug intraperitoneally. A
      significant decrease of the central effect of mianserin (30 mg kg-1) was seen in
      mice with experimental inflammation when compared with control animals (reaction
      time (s) = 12.12 +/- 1.22 vs 25.56 +/- 2.92; P less than 0.001) and the dose
      analgesia response curve (10-60 mg kg-1) was significantly shifted to the right
      in mice with inflammation. In serum of mice with inflammation, unbound
      concentration of mianserin was decreased from 19.37 +/- 0.73 to 17.83 +/- 0.30%
      (P less than 0.05) and seromucoid levels were significantly increased (P less
      than 0.001). Following the intraperitoneal administration of 30 mg kg-1 of
      mianserin, brain uptake decreased in diseased mice when compared with control
      animals (P less than 0.02), suggesting that the decrease in analgesia was
      secondary to a decrease in drug delivery to the brain because of increased
      protein binding.

PMID- 1359083
TI  - Effects of lithium and haloperidol on human sperm motility in-vitro.
AB  - Two psychotropic drugs, lithium and haloperidol, were evaluated for their in
      vitro effects on sperm motility using a transmembrane migration method. Sperm
      motility was measured either immediately after semen had been mixed with the drug
      or after a 2 h incubation period at 37 degrees C. Lithium inhibited human sperm
      motility in a dose-dependent manner with an EC50 of 10 mM when the semen-lithium
      mixture had been incubated. Sperm motility was increased to 127% of control when
      semen had been incubated with 0.027 microM haloperidol; this concentration was
      within the therapeutic range.

PMID- 1359084
TI  - Amorphism and physicochemical stability of spray-dried frusemide.
AB  - The physicochemical properties of amorphous forms of frusemide, prepared by spray
      drying at 50 or 150 degrees C, and their hygroscopic stability at temperatures of
      25 and 40 degrees C, and at 0 and 75% relative humidity were investigated. The
      glass transition temperature of the amorphous form A was 44.2 degrees C as
      measured by differential scanning calorimetry, while that of the amorphous form B
      was 54.4 degrees C. The activation energies for glass transition and
      crystallization processes were calculated from the differential scanning
      calorimetry thermograms of amorphous forms A and B, respectively. Stability
      determined by X-ray diffraction at 0% relative humidity, 25 and 40 degrees C
      suggested that form B was more stable than form A. However, the stability of form
      A at 75% relative humidity and 25 and 40 degrees C was similar to that of form B.

PMID- 1359085
TI  - Prediction of skin permeability of drugs: comparison of human and hairless rat
      skin.
AB  - Relationships between skin permeability and physicochemical properties of drugs
      were examined to establish a predictive method for the steady-state permeation
      rate of drugs through human skin. Human skin permeation properties fell into two
      categories: one in which the permeability coefficient is correlated to the
      partition coefficient, revealed with lipophilic drugs; and the other in which the
      permeability coefficients are almost constant, shown with hydrophilic drugs. The
      stratum corneum, the main barrier in skin, could be considered as a membrane with
      two parallel permeation pathways: lipid and pore pathways, and an equation for
      predicting the steady-state permeation rate of drugs was derived. The skin
      permeabilities of drugs for man were compared with those for hairless rat. The
      species difference in skin permeability found was suggested to be due to the
      difference in skin permeation pathways, since lipid content and water uptake of
      the stratum corneum varied between human and hairless rat skin.

PMID- 1359086
TI  - Pig ear skin as an in-vitro model for human skin permeability.
AB  - Pig skin has been shown to have similar histological and physiological properties
      to human skin and has been suggested as a good model for human skin permeability.
      In this series of experiments, the in-vitro permeability of pig ear skin was
      compared with human (abdominal) skin and rat (dorsal) skin using both hydrophilic
      (water, mannitol, paraquat) and lipophilic (aldrin, carbaryl, fluazifop-butyl)
      penetrants. Pig skin was found to have a closer permeability character than rat
      skin to human skin, particularly for lipophilic penetrants. Electrical
      conductivity measurements across pig skin membranes showed that skin conductivity
      could be a useful method for assessing the integrity of membranes, particularly
      when used in conjunction with water permeability assessments.

PMID- 1359087
TI  - Bile salt- and lysophosphatidylcholine-induced membrane damage in human
      erythrocytes.
AB  - The interaction of bile salts and lysophosphatidylcholine (LPC) with membranes
      has implications both in understanding the aetiology of a number of
      gastrointestinal disorders, including gastritis, gastric ulcers and colonic
      cancer, and in enhancing drug absorption by various epithelia. The membrane
      toxicity of nine bile salts (the sodium (S) salts of chenodeoxycholate (CDC),
      deoxycholate (DC) and cholate (C) and their glycine (G) and taurine (T)
      conjugates) and LPC was determined using erythrocyte haemolysis as a model
      parameter. Washed human erythrocytes were incubated for 15-60 min at 20 degrees C
      with media buffered at pH 8, 7 and 6. Bile salt toxicity was shown to be a
      function of type, concentration, pH and contact time with the membrane. At pH 7
      toxicity decreased in the order LPC greater than unconjugated dihydroxy salts
      (SDC and SCDC) greater than conjugated deoxycholates (SGDC and STDC) greater than
      conjugated chenodeoxycholates (SGCDC and STCDC) greater than unconjugated
      trihydroxy salt (SC) greater than conjugated trihydroxy salts (SGC and STC).
      Incubation with equimolar combinations of bile salts (SDC+SCDC; STCDC+SGDC;
      SDC+STDC) indicated that the resultant damage was an additive function of the
      damage induced by the individual bile salts.

PMID- 1359088
TI  - The mitigating effects of phosphatidylcholines on bile salt- and
      lysophosphatidylcholine-induced membrane damage.
AB  - The effects, at pH 7.0, of a series of 0.2 mM phosphatidylcholines (PC), namely
      dicaproyl-PC (DCPC), didecanoyl-PC (DDPC), dilauroyl-PC (DLaPC), dimyristoyl-PC
      (DMPC), dipalmitoyl-PC (DPPC), dioleoyl-PC (DOPC) and dilinoleoyl-PC (DLPC) and a
      series of 0.2 mM fatty acid salts (namely sodium myristate, palmitate, stearate,
      oleate and linoleate) upon the erythrocyte haemolysis induced by 2 mM sodium
      taurodeoxycholate (STDC) were determined. The influence of egg PC and dihexadecyl
      phosphate (DHDP) concentration upon the haemolysis induced by 1.4 mM sodium
      deoxycholate (SDC), 2 mM STDC and 0.1 mM lysophosphatidylcholine (LPC) were also
      established. A bile salt:egg PC mole ratio of 0.5 virtually abolished the
      haemolysis induced by SDC and STDC, whereas the same ratio of LPC:egg PC only
      reduced haemolysis from 65 to 40% (maximum haemolysis). DHDP had no effect on the
      haemolytic action of SDC or STDC. The salts of the fatty acids were non
      haemolytic, and when mixed with STDC did not affect the level of haemolysis
      induced by the bile salt. In contrast, DDPC and DLaPC enhanced the haemolysis of
      STDC and DCPC had no effect, whereas DMPC, DPPC, DSPC, DOPC, DLPC and egg PC all
      reduced haemolysis. Maximum reduction was determined for DMPC and egg PC. The
      mixed micelle preparation temperature (either room or 60 degrees C) and
      temperature of incubation (either 20 degrees C for 30 min or 37 degrees C for 5
      min) had only minor effects on the net haemolysis induced by STDC. These findings
      may be of significance in understanding the aetiology of certain gastrointestinal
      diseases and in determining whether mixed bile salt micelles have a role as drug
      penetration enhancers.

PMID- 1359089
TI  - Adsorption of paracetamol and chloroquine phosphate by some antacids.
AB  - The adsorption of paracetamol and chloroquine phosphate onto some antacids with
      adsorptive properties, has been studied. Dissolution of the drugs from commercial
      tablets was significantly retarded in the presence of the antacids. The
      adsorption and retardation of dissolution of both drugs by the adsorbent antacids
      studied followed the rank order magnesium trisilicate greater than magnesium
      oxide greater than aluminium hydroxide greater than edible clay. The concomitant
      administration of the drugs and antacid formulations containing any of these
      should be discouraged.

PMID- 1359090
TI  - Concentration-dependent exsorption of quinidine in the rat intestine.
AB  - During intravenous infusion, the luminal concentration of quinidine was higher
      than the plasma concentration. The intestinal clearance (CLi) of the drug was
      measured by dividing the rate of appearance of the drug in the intestinal luminal
      perfusate by the plasma concentration. The CLi of quinidine was therefore much
      higher than the rate of luminal perfusion. Over the infusion dose range of 0.1-2
      mg h-1, the CLi of quinidine decreased with increasing plasma concentration of
      quinidine. Adding quinidine into the luminal perfusate had little effect on the
      CLi of quinidine. Co-administration of quinidine with other agents intravenously
      did not alter the CLi of salicylic acid and urea, while the same treatment
      decreased the CLi of theophylline and S-disopyramide. In-vitro experiments on
      brush-border membrane vesicles showed that quinidine decreased the rate of Na+
      uptake and H+ efflux. The inhibition was significant at quinidine concentrations
      above 20 microM. Quinidine was a more potent inhibitor than amiloride. At
      quinidine infusion rates less than 2 mg h-1, quinidine concentration in plasma or
      in the luminal perfusate was at the lower limit of the inhibitory concentration.
      Microclimate pH at the intestinal surface was also measured. At mid-jejunum, the
      microclimate pH increased 0.3 pH units by infusing 2 mg h-1 of quinidine, while
      the microclimate pH at most other measuring sites was not significantly altered
      by quinidine infusion. It was concluded that quinidine is exsorbed from blood
      into the intestinal lumen by a carrier-mediated pathway in addition to the
      passive diffusion. At high plasma concentration, quinidine exsorption becomes
      saturated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359091
TI  - Effects of isosorbide-5-mononitrate and isosorbide-2-mononitrate on the
      contractile and electrical activity and on the content of cyclic nucleotides in
      isolated heart muscles of the guinea-pig and dog.
AB  - Isosorbide-5-mononitrate and isosorbide-2-mononitrate, the metabolites of
      isosorbide dinitrate, were studied for their effects on the contractile and
      electrical activity and on the content of cyclic nucleotides in isolated heart
      muscles of guinea-pig and dog. Isosorbide-5-mononitrate at all concentrations
      tested and isosorbide-2-mononitrate at low concentrations did not produce
      significant changes in the mechanical activity of guinea-pig heart preparations.
      Isosorbide-2-mononitrate in concentrations above 10(-4) M inhibited the
      contractility and shortened the action potential of guinea-pig and dog heart
      muscle. Neither mononitrate had an effect on cAMP concentration but both induced
      a significant elevation of cGMP content in guinea-pig heart tissue, the effect of
      isosorbide-2-mononitrate being greater.

PMID- 1359093
TI  - Urinary excretion of ephedrine after nasal application in healthy volunteers.
AB  - The urinary excretion of ephedrine after intranasal administration of the drug
      was studied in 8 healthy volunteers. Ephedrine (6 drops of a commercial 0.75%
      nasal ephedrine solution in each nasal cavity) was administered 4 times at
      intervals of 2 h (total amount applied equivalent to approximately 14 mg
      ephedrine), and urine was collected each hour for 10 h; the volunteers exercised
      on a bicycle ergometer at 50% of their VO2max for 2 h after the last ephedrine
      application. Ephedrine was detected in all urine samples. The urinary ephedrine
      concentration ranged from 0.9 to 16.5 micrograms mL-1; the number of urine
      samples with an ephedrine concentration exceeding 5 micrograms mL-1 ranged from
      1/10 (volunteer 2) to 9/10 (volunteers 1 and 3). The mean percentage of dose
      recovered within 10 h was 33% (range 23-50%). There was a weak but significant
      negative correlation between urinary pH and amount of ephedrine in the urine;
      exercise did not consistently influence the urinary amount. These results
      illustrate the systemic availability of ephedrine upon intranasal administration
      and show that the therapeutic use of a nasal ephedrine formulation by an athlete
      on the day of a competition can lead to a urinary ephedrine concentration above 5
      micrograms mL-1, which is considered positive in current doping regulations of
      the International Union of Cyclists.

PMID- 1359092
TI  - Vasorelaxation of rat thoracic aorta caused by two Ca(2+)-channel blockers, HA-22
      and HA-23.
AB  - The pharmacological effects of HA-22 (2-(4'methoxyphenylmethyl)-3,4
      dimethylpyrano[2,3-c]pyrazol- 6(2H)-one) and HA-23 (2-(2'-thienylmethyl)-3,4
      dimethylpyrano[2,3-c]pyrazol-6(2H) -one) on rat isolated thoracic aorta have been
      examined. In high potassium medium (60 mM), Ca2+ (0.03-3 mM)-induced
      vasoconstriction was inhibited by HA-22 and HA-23 (10-100 micrograms mL-1).
      Cromakalim-relaxed aortic rings precontracted with 15 mM but not 60 mM K+.
      However, HA-22, HA-23 and verapamil produced a greater relaxation in 60 mM than
      in 15 mM K(+)-induced contraction. The tonic contractions elicited by KCl (60 mM)
      and Bay K 8644 (10(-7)M) were also relaxed by the addition of HA-22 and HA-23.
      The phenylephrine concentration-response curves displayed antagonism by HA-22 and
      HA-23 (10-100 micrograms mL-1) in a non-competitive manner. The caffeine (10 mM)
      induced contraction and cAMP or cGMP levels were not affected by HA-22 or HA-23.
      It is concluded that HA-22 and HA-23 relaxed the rat aorta by suppressing the
      Ca2+ influx through both voltage-dependent and receptor-operated Ca2+ channels.

PMID- 1359094
TI  - Correlation of extrusion forces, raw materials and sphere characteristics.
AB  - This communication reports on the correlation between extrusion forces and sphere
      characteristics. Dicalcium phosphate dihydrate, alpha-lactose monohydrate and
      anhydrous beta-lactose were models for respectively an insoluble, a medium
      soluble and a highly soluble drug and were used to produce spheres. Phase
      diagrams for ternary mixtures consisting of microcrystalline cellulose, water and
      a third excipient were constructed. The region where good spheres were obtained
      correlated well with the area of extrusion forces between 630 and 1260 N. This
      correlation was seen for the insoluble, the medium and the highly soluble
      products.

PMID- 1359095
TI  - Effect of compressional forces on piroxicam polymorphs.
AB  - The effect of compressional force on the polymorphic transition in piroxicam has
      been examined, using pure polymorph, by differential scanning calorimetry, powder
      X-ray diffractometry and by determination of dissolution rates from tablets of
      the individual polymorphs. The needle shaped polymorph was found to undergo
      transition to the cubic polymorph during compression.

PMID- 1359096
TI  - Visual recovery using small dilating eye drops.
AB  - It is well established that reduced size dilating eye drops of 1% tropicamide and
      10% phenylephrine (micro drops) are effective for clinical purposes. Excellent
      pupil dilatation (mydriasis) is achieved and pupil constriction does not occur in
      response to light. In this study, the effect of micro drops of 1% tropicamide on
      distance and near visual recovery was compared with standard drops in a group of
      20 healthy volunteers. For each person studied, one eye was selected at random to
      be tested first with the standard drop size, and then after a minimum of one
      week, the same eye was again tested using a drop of the same drug one fifth
      standard size. An iris photograph, Snellen visual acuity at 6 m, and reading
      visual acuity was obtained for each test procedure: before drop instillation and
      at 30 min, 1, 2 and 4 h after drug instillation. Use of the micro drops caused a
      small but statistically significant improvement in the rate of recovery of
      distance and near visual acuity. These findings, allied to the known beneficial
      effects of reduced systemic absorption using micro drops, lend further weight to
      the argument that mydriasis may be achieved more safely, with fewer side effects,
      and with earlier return of normal vision when reduced size drops are used. It is
      hoped that practical micro drop dispensers will be developed.

PMID- 1359097
TI  - Comparison of salivary fluoride concentrations after administration of a
      bioadhesive slow-release tablet and a conventional fluoride tablet.
AB  - The in-vitro and in-vivo fluoride release of bioadhesive, slow-release tablets
      prepared from a mixture of polyethylene glycol polymers, containing 0.1 mg of
      fluoride as NaF was studied, and their ability to sustain fluoride levels in
      saliva were compared with conventional fluoride tablets with the same fluoride
      content. In-vitro release experiments showed that the bioadhesive tablets needed
      8 h to release all their fluoride compared with less than 1 h for the
      conventional fluoride tablets. In-vivo, the bioadhesive tablets had a retention
      period of 6 h and could sustain a salivary fluoride level of more than 10 microM
      above the baseline for 7 h. The conventional fluoride tablets achieved a peak
      concentration of 0.5 mM directly after dissolution in the mouth, but the fluoride
      level could not be sustained for longer than 1 h. A good agreement was found
      between the in-vitro swelling behaviour of the bioadhesive tablets and their in
      vitro and in-vivo release characteristics and their in-vivo retention time.

PMID- 1359098
TI  - Dispositional study of opioids in mice pretreated with sympathomimetic agents.
AB  - Brain and plasma levels of morphine and codeine were determined by an assay
      method involving solid-phase extraction and ion-pair reversed phase HPLC.
      Detection was by a variable wavelength UV-detector (for codeine) and an
      amperometric electro-chemical detector (for morphine) coupled in series.
      Ephedrine or phenylpropanolamine pretreatment did not interfere with the plasma
      disposition of morphine, evidenced by overlapping plasma concentration-time
      profiles. Brain opioid levels were equally unaffected by sympathomimetic
      pretreatment. The relative ratios of brain to plasma concentrations at the time
      corresponding to the respective peak anti-nociceptive activity for morphine and
      codeine revealed no significant differences. It is concluded that single doses of
      ephedrine and phenylpropanolamine do not affect the disposition of morphine and
      codeine in mice.

PMID- 1359099
TI  - HI-6 pharmacokinetics in rabbits after intravenous and intramuscular
      administration.
AB  - The pharmacokinetics of HI-6 ((4-carboxamidopyridinium (1) methyl)-(2'
      hydroxyiminomethyl-pyridinium (1') methyl) ether dichloride) have been studied in
      rabbits receiving an intramuscular (50 micrograms kg-1) or intravenous (12.5
      micrograms kg-1) dose. The plasma concentration-time profile for the
      intramuscular dose (n = 8) fits a one-compartment open model with first-order
      absorption and elimination. The absorption half-life was 2 min and maximum
      concentration (51 micrograms mL-1) was reached in 9 min. The pharmacokinetics for
      the intravenous dose (n = 8) was described by a two-compartment open model with
      first-order distribution and elimination. The apparent volume of distribution was
      0.1 L kg-1. Half-lives of distribution and elimination were 5 and 38 min,
      respectively. The results indicate HI-6 is rapidly absorbed, distributed and
      eliminated in rabbits receiving an intramuscular dose.

PMID- 1359100
TI  - Effects of senna and its active compounds rhein and rhein-anthrone on PAF
      formation by rat colon.
AB  - A single or a prolonged oral administration of senna (60 mg kg-1) to rats did not
      increase either colonic PAF (platelet activating factor) content or intraluminal
      release of acid phosphatase. A similar result was observed in the colonic tissue
      of rats perfused in-vitro with rhein (1-300 micrograms mL-1) or rhein-anthrone (1
      300 micrograms mL-1). A single or prolonged administration of castor oil (2 mL)
      to rats increased both colonic PAF content and intraluminal release of acid
      phosphatase. Colonic tissue of rats perfused in-vitro with calcium ionophore
      A23187 (1 and 10 micrograms mL-1) formed large amounts of PAF and acid
      phosphatase. Since PAF can mediate intestinal damage and acid phosphatase is a
      marker of cellular injury, we conclude that senna and its derivatives, rhein and
      rhein-anthrone, are well tolerated in rats.

PMID- 1359101
TI  - Anorectic activity of fluoxetine and norfluoxetine in mice, rats and guinea-pigs.
AB  - The present study aimed to establish the role of the metabolite norfluoxetine in
      the anorectic activity of fluoxetine, and to relate the anorectic doses (ED50) to
      the brain concentrations of the parent drug and its metabolite. Fluoxetine showed
      anorectic activity at increasing intraperitoneal doses (ED50 = 39.1, 34.7 and
      21.7 mumol kg-1 in mouse, rat and guinea-pig, respectively) and norfluoxetine was
      slightly more active (24.3, 22.9 and 19.1 mumol kg-1, respectively) in all three
      species. In terms of maximum concentration (Cmax) and area under the curve (AUC)
      within the experimental period (0-90 min), brain concentrations varied widely and
      were poorly related to the dose; guinea-pig appeared to be much more sensitive to
      fluoxetine than was mouse or rat. Administered norfluoxetine was present in the
      brain of the three species in approximately the same order as fluoxetine, i.e.
      lower in guinea-pig than in mouse or rat. The Cmax and AUC of norfluoxetine after
      fluoxetine administration was 50-60% of the values after an equiactive dose of
      norfluoxetine in mouse and guinea-pig, and more than 80% in rat.

PMID- 1359102
TI  - Further studies on the anti-nociceptive effect of vasopressin.
AB  - The possible interactions of pathways which mediate anti-nociception when
      stimulated by alpha 2-adrenoceptor agonists and arginine vasopressin (AVP) were
      investigated. Yohimbine, an alpha 2-antagonist, failed to modify the anti
      nociceptive response of AVP. However, clonidine pretreatment, in sub-effective
      and effective doses, potentiated the anti-nociceptive response of a sub-effective
      dose of AVP. This potentiation was attenuated by yohimbine and completely
      antagonized by naloxone. These studies suggest that pathways related to the
      opioidergic system and those stimulated by alpha 2-agonists may be utilized by
      AVP in eliciting the anti-nociceptive response.

PMID- 1359104
TI  - The effect of thymidine on the antibacterial and antiviral activity of
      zidovudine.
AB  - The effect of thymidine and deoxyadenosine on the antiviral and antibacterial
      effect of zidovudine was studied in human immunodeficiency virus type 1 (HIV-1)
      Escherichia coli and Salmonella typhimurium. In quantitative assays, 10
      micrograms mL-1 thymidine was shown to increase the 50% inhibitory concentration
      (IC50) of zidovudine for HIV-1 by approximately 100-fold and to reduce zidovudine
      (1 microM)-induced protection of C8166 cells from 2.04 to 0.18 log syncytial
      forming units. Thymidine also antagonized the antibacterial effect of zidovudine
      for two E. coli and three S. typhimurium species in a dose-dependent manner; 10
      micrograms mL-1 of thymidine increased the minimum inhibitory concentration of
      zidovudine for E. coli strains by 10-40-fold and for S. typhimurium strains by
      three-fold. Deoxyadenosine reduced the minimum inhibitory concentration of
      zidovudine against all five bacterial strains but had no effect on the IC50 of
      zidovudine for HIV-1, nor did it significantly reverse the antagonism of the
      antibacterial and antiviral activity of thymidine. The induction of the SOS
      response in E. coli was reversed in a dose-dependent manner by thymidine while
      the presence of deoxyadenosine increased induction of the SOS response by
      zidovudine at suboptimal concentrations.

PMID- 1359103
TI  - Effects of benzodiazepine administration on A1 adenosine receptor binding in-vivo
      and ex-vivo.
AB  - The adenosine receptor has been implicated in the central mechanism of action of
      benzodiazepines. The specific binding of an A1-selective adenosine antagonist
      radioligand, [3H]8-cyclopentyl-1,3-dipropylxanthine, was measured in-vivo in mice
      treated with alprazolam (2 mg kg-1, i.p.), lorazepam (2 mg kg-1, i.p.) and
      vehicle. Binding studies were performed in-vivo and ex-vivo in mice receiving
      continuous infusion of alprazolam (2 mg kg-1 day-1), lorazepam (2 mg kg-1 day-1)
      and vehicle by mini-osmotic pumps for 6 days. Continuous infusion of alprazolam
      and lorazepam significantly decreased specific binding by 34 and 53%,
      respectively, compared with vehicle treatment (P less than 0.01). Single doses of
      alprazolam and lorazepam induced a similar trend in specific binding in-vivo (P =
      0.07). There were no alterations in A1-receptor density (Bmax) or affinity (Kd)
      in cortex, hippocampus or brainstem in ex-vivo studies. Benzodiazepine treatment
      may diminish A1- receptor binding in-vivo by inhibiting adenosine uptake or by
      direct occupancy of the A1 adenosine receptor recognition site.

PMID- 1359105
TI  - Organic cation transport and cationic drug interactions in freshly isolated
      proximal tubular cells of the rat.
AB  - Freshly isolated proximal tubular cells (PTC) of the rat are used to study the
      uptake of a prototypical organic cation, tetraethylammonium (TEA), and the
      influence of other cationic drugs on TEA uptake. The time dependency of 50 microM
      TEA uptake was determined by incubating PTC for time periods from 10 sec until 60
      min. TEA uptake was linear for at least 2 min and reached equilibrium after 30
      min. The cell to medium ratio reached a value of 8 after 60 min, indicating
      marked accumulation of TEA. TEA uptake was concentration dependent and saturable,
      with an apparent Km of 63 +/- 7 microM and Vmax of 0.57 +/- 0.02 nmol/mg
      protein.min. In comparison with cells cultured on filters, the overall transport
      characteristics of TEA in PTC seem to resemble basolateral to apical flux. The
      concentration-dependent inhibition of some H2 antagonists and various cations on
      32 microM TEA uptake was investigated, as well as the interaction with
      probenecid. Analysis of the log-concentration inhibition curves showed that
      mepiperphenidol, trimethoprim, famotidine and cimetidine had a high and low IC50
      value, whereas ranitidine, nizatidine, cimetidine sulfoxide, N1
      methylnicotinamide and probenecid had only a low IC50 value. The data reported
      here are comparable with those from other preparations, and it is possible to
      extrapolate to the human in vivo situation. Moreover, the isolation procedure is
      relatively simple and quick and the yield is high.

PMID- 1359106
TI  - Vascular alpha-1 antagonistic and agonistic effects of beta adrenoceptor agonists
      in rabbit common carotid arteries.
AB  - The stainless-steel cannula-inserting method was used to observe vascular effects
      of mixed and selective beta adrenoceptor agonists, isoproterenol, procaterol and
      denopamine, on isolated, perfused rabbit common carotid arteries. In
      phenylephrine-preconstricted preparations, the three beta agonists induced a dose
      dependent vasodilation which was not suppressed by treatment with beta
      antagonists, atenolol, a selective beta-1 antagonist and ICI 118551, a selective
      beta-2 antagonist. On the other hand, in prostaglandin F2 alpha-preconstricted
      preparations, these agonists produced no vasodilation and revealed weak
      vasoconstrictions which were readily suppressed by bunazosin, a selective alpha-1
      antagonist. Moreover, these agonists caused a shift of the dose-response curve
      for phenylephrine to the right in a parallel fashion in non-preconstricted
      preparations. The relative pA2 values for isoproterenol, procaterol and
      denopamine calculated from the displacement curve were 7.47, 7.59 and 8.17,
      respectively. Thus, it is concluded that 1) there are little functional beta
      adrenoceptors in the rabbit common carotid arteries, 2) beta adrenoceptor
      agonists have both antagonistic and agonistic properties for alpha-1 adrenoceptor
      activation, 3) denopamine possesses a higher potency as an alpha-1 antagonist and
      4) beta agonists generally act as vasodilators in rabbit cerebral circulation.

PMID- 1359107
TI  - Comparative effects of receptor inactivation, 17 beta-estradiol and pertussis
      toxin on dopaminergic inhibition of prolactin secretion in vitro.
AB  - Akin to receptor inactivation with phenoxybenzamine (PBZ) (1 microM, 1 hr),
      treatment of anterior pituitary cells with 17 beta-estradiol (10 nM, 3 days)
      right-shifted the dose-response curve for inhibition of prolactin (PRL) secretion
      by the full agonist R-(-)-N-n-propylnorapomorphine (NPA) and reduced the maximal
      effect [EC50 (pM) and percent maximal effect: control, 25.4 and 81.2; PBZ, 115.3
      and 57.9; 17 beta-estradiol, 358 and 58.6]. PBZ treatment of 17 beta-estradiol
      pretreated cultures further reduced the maximal response but did not alter the
      EC50. Plots of receptor occupancy vs. response indicated a large receptor reserve
      for NPA (approximately 60%) in control cultures but its abolition by 17 beta
      estradiol. 17 beta-Estradiol pretreatment elicited identical rightward shifts
      (4.5-fold) and similar reductions in maximal PRL inhibition by quinpirole and (+)
      3-PPP, although these drugs were partial agonists with dissimilar efficacies
      relative to NPA (0.61 and 0.12, respectively) at presynaptic striatal D2
      receptors. However, receptor inactivation experiments with (+)-3-PPP and
      quinpirole, and subsequent comparison of receptor occupancy vs. response plots,
      demonstrated that the relative efficacies of quinpirole and (+)-3-PPP were
      reversed in the striatum and anterior pituitary. In striatum, half-maximal
      response to quinpirole and (+)-3-PPP required 6.2 and 30% receptor occupancy,
      respectively, whereas 25.6 and 9.6% occupancy was required in the pituitary.
      Pertussis toxin treatment (10 ng/ml, 24 hr) produced large shifts in the dose
      response curves for all three agonists (8.4-21.9-fold), but was distinguished
      from the effects of both PBZ and 17 beta-estradiol by a significant (P < .001)
      decrease in the slope factor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359108
TI  - Norepinephrine and alpha-2 adrenoceptors modulate active ion transport in porcine
      small intestine.
AB  - The effects of norepinephrine (NE) were examined on active ion transport in the
      porcine distal jejunum under base-line conditions and after electrical transmural
      stimulation (ETS). Serosal administration of NE decreased basal short-circuit
      current across sheets of muscle-stripped jejunal submucosa-mucosa in vitro. These
      effects were absent in tissues pretreated with the neuronal conduction blocker,
      tetrodotoxin. NE stimulated net Na secretion in tissues which displayed basal net
      Na and Cl absorption and increased net Cl absorption in tissues which displayed
      net Na absorption and Cl secretion under base-line conditions. Moreover, NE
      inhibited short-circuit current elevations produced by ETS (300 pulses at 10 Hz,
      0.5 msec pulse duration, 2.8 mA cm-2), the ganglionic stimulant dimethylphenyl
      piperazinium or the gut peptide neurotensin. In contrast, NE did not alter
      mucosal responses to the directly acting secretagogues forskolin and carbachol.
      The inhibitory action of NE on mucosal responses evoked by ETS were selectively
      antagonized by the alpha adrenoceptor blockers phentolamine and yohimbine.
      Moreover, the selective alpha-2 adrenoceptor agonists p-aminoclonidine, UK-14,304
      and oxymetazoline and the NE releasing agent tyramine mimicked the inhibitory
      effects of NE on ETS-evoked mucosal responses. Desipramine, a blocker of neuronal
      NE uptake, produced a 1000-fold increase in the potency of NE at concentrations
      less than 1 nM. These results suggest that NE modulates active ion transport by
      interacting with alpha-2 adrenoceptors located on submucosal neurons of the
      porcine small intestine.

PMID- 1359109
TI  - Yohimbine as a serotonergic agent: evidence from receptor binding and drug
      discrimination.
AB  - Stimulus control was established in rats trained to discriminate either 8-hydroxy
      2-(di-n-propylamino)tetralin (DPAT) (0.2 mg/kg) or yohimbine (3 mg/kg) from
      saline. Tests of generalization were then conducted with a group of drugs thought
      to act via the 5-hydroxytryptamine1A (5-HT1A) receptor and a group of drugs
      thought to act as antagonists at alpha 2 adrenoceptors. In addition, each drug
      was characterized in terms of its affinity for 5-HT1A and alpha 2 adrenoceptors
      by means of radioligand binding techniques. It was observed that the stimulus
      effects of DPAT generalized fully to those of the alpha 2-adrenoceptor
      antagonists, yohimbine, rauwolscine and L-657,743, but not to idazoxan or
      atipamezole. The dissociation constants (Kd, nM) of the alpha 2-adrenoceptor
      antagonists at the 5-HT1A receptor were 74, 52, 80, 199 and 13,000, respectively.
      Thus, the discrimination data are explicable in terms of a direct action of
      yohimbine and some other alpha 2 adrenoceptor antagonists upon 5-HT1A receptors.
      In yohimbine-trained rats, full generalization to DPAT, flesinoxan and
      tandospirone was observed. In light of the negligible affinity of flesinoxan and
      tandospirone for the alpha 2 adrenoceptor (9000 and 8800 nM, respectively), and
      high affinity for the 5-HT1A receptor (0.3 and 43 nM, respectively), a mechanism
      mediated by the latter site is suggested. We would emphasize two implications of
      the present study. First, the present data suggest that rats trained with
      yohimbine as a discriminative stimulus generalize to drugs with minimal affinity
      for the alpha 2 adrenoceptor but with high affinity for 5-HT1A
      receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359110
TI  - Hemodynamic and sedative effects of dexmedetomidine in dog.
AB  - This study investigated hemodynamic and sedative effects of a single dose of the
      selective alpha-2 adrenoceptor agonist dexmedetoimidine (DMED) in isoflurane
      anesthetized dogs. DMED (20 micrograms/kg i.v. 2-min infusion) was given to all
      dogs. In Group 1 the effects of DMED (time control; N = 10) were studied over 4
      hr. In Group 2 (N = 11) glycopyrrolate (40 micrograms/kg initial dose followed by
      20 micrograms/kg repeated every 30 min) was used to modulate the DMED-induced
      vagally mediated changes in heart rate. In Group 3 (N = 8), two doses of
      nifedipine were used to offset the DMED-induced increase in arterial blood
      pressure, low dose nifedipine = 10 micrograms/kg bolus followed by 2.5
      micrograms/kg/min infusion for 20 min, high dose nifedipine = 20 micrograms/kg
      bolus followed by 5 micrograms/kg/min infusion for 20 min. DMED administration
      reduced isoflurane anesthetic requirements by 89% at 30 min and by 50% at 4 hr.
      Maximum increase in mean arterial blood pressure (MABP) +67 mm Hg occurred 1 min
      after DMED. MABP remained significantly elevated throughout the 4 hr studied
      (about +20%). Concomitant with the transient peak in MABP, heart rate (129 +/- 6
      to 60 +/- 8 bpm) and cardiac output (3.5 +/- 0.3 to 0.9 +/- 0.1 l/min) decreased,
      whereas systemic vascular resistance (2460 +/- 210 to 14,700 +/- 1330
      dynes.sec.cm-5) and left ventricular end diastolic pressure (4 +/- 1 to 27 +/- 4
      mm Hg) increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359111
TI  - Inhibitory effects of the antiparkinsonian drugs memantine and amantadine on N
      methyl-D-aspartate-evoked acetylcholine release in the rabbit caudate nucleus in
      vitro.
AB  - Slices of the rabbit caudate nucleus were incubated with [3H]choline or
      [3H]dopamine and then superfused continuously with Mg(++)-free medium.
      Stimulation with N-methyl-D-aspartate (NMDA), alpha-amino-2,3-dihydro-5-methyl-3
      oxo-4-isoxazolepropanoic acid (AMPA), L-glutamate and kainic acid (in that rank
      order of potencies) caused a concentration-dependent increase in [3H]ACh efflux,
      which was abolished in the presence of Mg++. This kind of release was Ca(++)
      dependent and tetrodotoxin-sensitive. In contrast, NMDA was hardly effective in
      stimulating [3H]ACh release from hippocampal or cortical slices, as well as
      [3H]dopamine release from slices of rabbit caudate nucleus. Hence, the presence
      of cell bodies of stimulated neurons seems to be a prerequisite for the induction
      of release via NMDA receptors. Dizocilpine [(+)-5-methyl-10,11-dihydro-5H
      dibenzo(a,d)cyclohepten-5,10-imine maleate] at nanomolar concentrations, as well
      as memantine and amantadine at low micromolar concentrations, inhibited the L
      glutamate- and NMDA-evoked [3H]ACh release in a concentration-dependent,
      noncompetitive and use-dependent manner. Also (+/-)-2-amino-5-phosphopentanoic
      acid at micromolar concentrations depressed the L-glutamate- and NMDA-induced
      release, acting, however, in a competitive manner. It is concluded that, by
      antagonizing NMDA receptor-mediated ACh release, memantine and amantadine may act
      as functional "anticholinergics" when administered clinically to treat
      Parkinson's disease.

PMID- 1359112
TI  - Mu opioid receptors are associated with the induction of hippocampal mossy fiber
      long-term potentiation.
AB  - We assessed the effects of antagonists selective for mu (mu), delta (delta) or
      kappa (kappa) opioid receptors on the induction of long-term potentiation (LTP)
      and short-term potentiation (STP) at the rat hippocampal mossy fiber-CA3 synapse
      in vivo. The mu opioid receptor-selective antagonist Cys2,Tyr3,Orn5,Pen7 amide
      (CTOP, 1 or 3 nmol) did not alter either mossy fiber-CA3 responses evoked at low
      frequencies or previously potentiated mossy fiber-CA3 responses, but it
      attenuated the induction of mossy fiber LTP in a dose-dependent manner. By
      contrast, LTP of CA3 responses evoked by stimulation of commissural afferents to
      the CA3 region was unaffected by CTOP. Neither the delta opioid receptor
      selective antagonist naltrindole hydrochloride (0.3-10 nmol) or the kappa opioid
      receptor-selective antagonist nor-binaltorphimine hydrochloride (3-10 nmol)
      altered the induction of mossy fiber LTP. Thus, a role for delta or kappa opioid
      receptors in the induction of mossy fiber LTP could not be demonstrated. CTOP, in
      quantities that attenuated mossy fiber LTP induction, also attenuated the
      magnitude of mossy fiber STP measured 5 sec after delivery of conditioning
      trains. Further examination of the component of STP corresponding to post-tetanic
      potentiation (PTP) revealed that CTOP selectively attenuated the estimated
      magnitude and time constant of decay of mossy fiber PTP. These results suggest
      that the frequency-dependent activation of mu opioid receptors by endogenous
      opioid peptides is required for the induction of LTP at hippocampal mossy fiber
      synapses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359113
TI  - Adrenergic mechanisms underlying cardiac and vascular responses to cocaine in
      conscious rats.
AB  - The contribution of adrenergic receptors to the cardiovascular responses to
      cocaine (5 mg/kg i.v.) were examined in conscious, free-moving rats instrumented
      for continuous measurement of arterial pressure, heart rate and blood flows in
      the mesentery and hindquarters or ascending aorta. Cocaine elicits an immediate
      (peak) and sustained pressor response with a concomitant reduction in heart rate.
      Prazosin (0.1 mg/kg i.v.) pretreatment significantly reduced both the peak and
      sustained pressor responses by attenuating the increases in systemic, mesenteric
      and hindquarters vascular resistances. Idazoxan pretreatment (1 mg/kg i.v.)
      attenuated the peak increase in hindquarters vascular resistance. Whereas
      propranolol pretreatment (1 mg/kg i.v.) attenuated the peak pressor response, the
      sustained pressor response was enhanced due to increased hindquarters and
      systemic vascular resistances. Metoprolol pretreatment (1 mg/kg i.v.) enhanced
      the sustained pressor response to cocaine, in part due to increased heart rate
      and mesenteric vascular resistances. Upon examination of the cardiac effects of
      cocaine, a sustained bradycardic response was observed, whereas stroke volume and
      cardiac output were relatively unaffected. The bradycardic response to cocaine
      was attenuated by yohimbine (0.1 mg/kg i.v.), prevented by prazosin and converted
      to a tachycardia after idazoxan (1 mg/kg) pretreatment. After propranolol
      pretreatment, cocaine substantially decreased cardiac output and stroke volume.
      Our results demonstrate that cocaine produces a biphasic pressor response in
      conscious rats and that the mechanisms underlying the dual responses vary in
      intensity and mode of action in different vascular beds, but are primarily
      dependent upon alpha-1 adrenergic receptor-mediated vasoconstriction.

PMID- 1359114
TI  - Somatostatin depleting potency of cysteamine-related thiols and amines in the
      rat: structure-activity relation.
AB  - Cysteamine, a potent duodenal ulcerogen, stimulates gastric acid and gastrin
      secretion and decreases immunoreactive somatostatin (IRS) from the gut and
      hypothalamus of the rat. To elucidate the structural requirements for this
      effect, we tested a series of cysteamine analogs for their IRS decreasing
      activity in comparison with their nucleophilic and reducing potencies. Adult
      female rats were sacrificed 4 hr after p.o. administration of the test chemicals
      given in molar equivalents to 30 mg/100 g of cysteamine-HCl. IRS decreasing
      activity in gastric mucosa, expressed as percentage of controls is listed in
      descending order: cystamine (55%), cysteamine (59%), 2-dimethylaminethanethiol
      (59%), ethylamine (66%), 1,3-propanedithiol (70%), propylamine (75%) and 3
      aminothiophenol (79%). The following thiols and amines had no IRS decreasing
      effect (80% of controls): L-cysteine, ethanethiol, 1-propanethiol, penicillamine,
      dimercaprol, 1-4-dithiothreitol, ethanolamine, propionitrile, n-butyronitrile, o
      , m- or p-aminophenol. The aryl 2-, 3- or 4-aminothiophenols, unlike most of
      their aminophenol analogs also decreased immunoreactive prolactin in the
      pituitary by 38 to 78%. IRS decreasing activity was independent of the reducing
      potency of cysteamine derivatives but was correlated significantly (r = 0.793, P
      < .01) with electron affinity of -SH, -NH2, -OH and -CN radicals in terminal
      alkyl chemicals. The structural requirement for decreasing activity is the
      presence of either -SH and -NH2 on a 2 to 3 carbon alkyl or aryl molecule. Both
      radicals when present together increase potency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359115
TI  - Comparison of the role of local anesthetic properties with dopamine uptake
      blockade in the inhibition of striatal and nucleus accumbens [3H]acetylcholine
      release by cocaine.
AB  - The effects of cocaine on the electrically evoked release of tritium from brain
      slices previously loaded with [3H]choline were examined and used as an index of
      acetylcholine (ACh) release. In the striatum, cocaine dose-dependently inhibited
      ACh release, with an IC50 of 2.9 microM. At 10 microM cocaine, D2 receptor
      blockade by sulpiride resulted in only about a 45% reversal of the inhibition of
      ACh release, whereas inhibition due to either nomifensine or quinpirole was
      reversed by about 80%. 5-Hydroxytryptamine antagonists had no effect on the
      cocaine-induced inhibition of striatal ACh release, thus suggesting no
      involvement of this amine in cocaine's action. Antagonists against gamma
      aminobutyric acidA, muscarinic, opioid and adenosine receptors were similarly
      ineffective at reversing cocaine's effect on ACh release. Comparison with the
      effect of procaine on striatal ACh release suggested that the inhibition of ACh
      release in the presence of sulpiride was due to the local anesthetic properties
      of cocaine. In the nucleus accumbens cocaine was about 5-fold less potent at
      inhibiting ACh release than in the striatum and sulpiride was much less effective
      at reversing the inhibitory effect of cocaine, suggesting that the local
      anesthetic effects of cocaine play a greater role in regulating ACh release in
      this area relative to dopamine uptake blockade. These data suggest that the local
      anesthetic effect of cocaine is prominent at concentrations found in the central
      nervous system after pharmacologically relevant systemic doses and depending on
      the degree of monoaminergic control of a particular brain area, may be even more
      important than the effects of cocaine arising from inhibition of reuptake.

PMID- 1359116
TI  - Kinetic analysis of P-glycoprotein-mediated doxorubicin efflux.
AB  - P-glycoprotein lowers the intracellular concentration of a variety of unrelated
      compounds including doxorubicin by actively removing them from the cell.
      Mathematical modeling techniques have been applied to the transmembrane transport
      of doxorubicin in a nonresistant HL-60 cell line and in a P-glycoprotein
      containing resistant subclone, HL-60R, to obtain clearances for inward and
      outward transport. Distribution of [14C]doxorubicin from extracellular fluid into
      the cell pellet was analyzed with a closed two-compartment system that fitted
      experimental measurements of drug concentrations in the extracellular fluid and
      in the cell pellet, represented by a third compartment that includes trapped
      extracellular doxorubicin along with the intact cells. Transmembrane diffusion
      clearance was similar for the two cell lines (1.00 vs. 1.06 microliters sec-1),
      yielding an apparent doxorubicin permeability coefficient of 7.4 x 10(-5) cm sec
      1. However, the total efflux clearance averaged 0.99 +/- 0.05 microliters sec-1
      in HL-60 and 2.29 +/- 0.62 microliters sec-1 in HL-60R. The estimated P
      glycoprotein-mediated efflux clearance in HL-60R averaged 1.23 +/- 0.51
      microliters sec-1. This experimental approach provides direct estimates of
      transport parameters in intact cells and should be useful in studying the
      mechanism of action and interactions of inhibitors of P-glycoprotein.

PMID- 1359117
TI  - Selective M3 muscarinic receptor antagonists inhibit smooth muscle contraction in
      rabbit trachea without increasing the release of acetylcholine.
AB  - Although five muscarinic receptor subtypes have now been cloned, only three
      receptor subtypes have been demonstrated pharmacologically in bronchial tissue
      (designated M1, M2 and M3). By using drugs that show selectivity for these
      receptor subtypes, in combination with a sensitive and specific high-pressure
      liquid chromatography method that enables the direct measurement of acetylcholine
      (ACh) release, the existence and function of these muscarinic receptor subtypes
      was investigated in rabbit trachea in vitro. Atropine and ipratropium bromide,
      nonselective antimuscarinic agents, dose-dependently suppressed contraction of
      rabbit trachea induced by transmural electrical stimulation, but at the same time
      enhanced the release of ACh, suggesting the presence of an autoregulatory feed
      back system. The M2/M4 receptor antagonists methoctramine, 11-((2
      [(diethylamino)methyl]-1-piperidinyl)acetyl)-5, 11-dihydro-6H-pyrido(2,3
      b)(1,4)benzodiazepine-6-one, 5,11-dihydro-11-([(2-(2-[(dipropylamino)methyl]-1
      piperidinyl)ethyl) amino]carbonyl)-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one and
      11-((4-[4-(diethylamino)butyl]-1-piperidinyl)acetyl)-5, 11-dihydro-6H-pyrido(2,3
      b)(1,4)benzodiazepine-6-one also dose-dependently increased ACh release during
      electrical stimulation, indicating that the powerful negative feedback system is
      mediated by presynaptic autoreceptors of the M2 or M4 type.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1359118
TI  - Effect of the dopamine D2 receptor agonist quinpirole on renal sympathetic nerve
      activity and renal norepinephrine spillover in anesthetized rabbits.
AB  - Cardiovascular and sympathetic nervous system effects of the dopamine D2 receptor
      selective agonist quinpirole were studied in anesthetized rabbits. Sodium
      nitroprusside was administered for comparison. The animals received a tracer
      infusion of [3H] norepinephrine i.v. Arterial and renal venous concentrations of
      endogenous norepinephrine and epinephrine and [3H]norepinephrine, the firing rate
      of the renal sympathetic nerves and renal blood flow were determined. Quinpirole
      (100 micrograms kg-1 + 5 micrograms kg-1 min-1 i.v.) lowered blood pressure and
      renal vascular resistance. The firing rate of the renal sympathetic nerves was
      increased, but there was no reflex tachycardia. Despite the increase in renal
      sympathetic firing, the renal spillover of norepinephrine into blood was
      decreased. The increase in total body norepinephrine spillover during quinpirole
      induced hypotension was less than expected from baroreflex activation. Effects of
      quinpirole were antagonized by domperidone (1000 micrograms kg-1 + 200 micrograms
      kg-1 h-1). The distinguishing feature of this study is the simultaneous
      measurement of sympathetic firing and norepinephrine spillover in the same organ,
      the kidney, under conditions of intact sympathetic impulse traffic. Quinpirole
      activated presynaptic D2 receptors and thus reduced the released norepinephrine
      per action potential. Consequences of the presynaptic inhibition were reductions
      of blood pressure and renal vascular resistance and absence of reflex
      tachycardia.

PMID- 1359119
TI  - Biochemical and functional identification of a novel dopamine receptor subtype in
      rat brown adipose tissue. Its role in modulating sympathetic stimulation-induced
      thermogenesis.
AB  - Various dopamine (DA) agonists including propylnorapomorphine, lisuride,
      bromocriptine, apomorphine and quinpirole were found to reduce adenylate cyclase
      activity in rat brown adipose tissue homogenates. These inhibitory effects were
      antagonized, with a very low stereoselectivity, by DA receptor antagonists with
      the following rank order of potency: haloperidol > (+)-butaclamol > or = (-)
      butaclamol >> clozapine > or = (-)-sulpiride > or = (+)-sulpiride > or =
      eticlopride, but not by the alpha-2 adrenoceptor antagonists, phenoxybenzamine
      and yohimbine or the serotonin receptor antagonists, ketanserin and metergoline.
      The selective D1 agonist, fenoldopam, was completely inactive in modifying the
      basal enzyme activity. DA as well as various DA agonists (lisuride >
      propylnorapomorphine > bromocriptine > apomorphine > quinpirole) dose-dependently
      reduced the stimulation of adenylate cyclase activity induced either by forskolin
      or by the beta adrenoceptor agonist, (-)-isoproterenol. Similar results were
      obtained also in dispersed brown adipocytes. We also found that DA and various DA
      receptor agonists induced a significant decrease of beta adrenoceptor-stimulated
      glycerol and nonesterified fatty acids release from brown adipocytes. This effect
      was selectively antagonized by haloperidol and butaclamol. Thus, the receptors
      present on the BAT membranes appear to be dopaminergic in nature although they
      differ from the classical D2 receptor for the following: 1) the low affinity for
      the most selective D2, D3 and D4 receptor agonist and antagonist (quinpirole,
      sulpiride and clozapine); 2) the absence of stereoselectivity for various DA
      antagonists (butaclamol and sulpiride); and 3) the lack of detectable mRNA
      encoding D2 or D3 DA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359120
TI  - Transport of digoxin by human P-glycoprotein expressed in a porcine kidney
      epithelial cell line (LLC-PK1).
AB  - This article represents the first evidence that the renal secretion of the
      commonly used drug, digoxin, is mediated by P-glycoprotein. In this study, it was
      demonstrated that digoxin is a substrate of P-glycoprotein, and the mechanism of
      a clinically important drug interaction, such as digoxin-quinidine, was
      elucidated. Human P-glycoprotein was expressed on the apical membrane of the
      porcine kidney epithelial cell line, LLC-PK1 by transfecting with human MDR1
      cDNA. The expression and function of P-glycoprotein were confirmed by Southern
      and Western blotting, RNase protection assay, immunostaining and transporting
      activity for vinblastine. The transepithelial transport of [3H]digoxin was
      measured across the cell monolayers grown on microporous polycarbonate membrane
      filters. The transfectant cells exhibited markedly greater basal-to-apical
      transport and less apical-to-basal transport than the host cells, and the former
      was 8-fold greater than the latter. The augmented transepithelial transport
      resulted from the increased efflux from cells to apical side. This oriented
      transport was inhibited by the presence of 20 microM vinblastine, quinidine or
      verapamil. The rate of efflux to the apical side was 2-fold greater than that to
      the basal side. Quinidine inhibited the efflux to the apical side but did not
      affect transport into the basal side. These findings demonstrate that digoxin is
      transported by human P-glycoprotein, which is a previously undiscovered drug
      transport system in the kidney other than organic cation and anion transport
      systems, and suggest a molecular mechanism for the renal tubular secretion of
      digoxin as well as clinically important digoxin-quinidine interaction via P
      glycoprotein.

PMID- 1359122
TI  - Somatosensory stimulation causes autonomic vasodilatation in cat lip.
AB  - 1. Electrical stimulation of the infra-orbital nerve and the maxillary buccal
      gingiva caused an increase in ipsilateral lip blood flow in a stimulus intensity
      dependent manner in anaesthetized cats. 2. The reflex vasodilator response was
      resistant to blockade by antimuscarinic (atropine), antiadrenergic (phentolamine
      and propranolol) and antihistaminergic (tripelennamine) but sensitive to
      ganglionic blocking agent (hexamethonium). 3. The reflex vasodilator response was
      unaffected by section of the ipsilateral cervical sympathetic trunk and facial
      nerve root, but was completely abolished by ipsilateral section of the
      glossopharyngeal nerve root. 4. The vasodilator response elicited by stimulation
      of the facial and glosso-pharyngeal nerves was never affected by lesion of the
      ipsilateral pterygopalatine ganglion. 5. Local anaesthesia or section of the
      inferior alveolar nerve abolished the vasodilator effects of stimulation of the
      facial and the glossopharyngeal nerves. 6. These results suggest that there is a
      somato-autonomic reflex vasodilator system mediated via final neurons that are
      not cholinergic, and that the parasympathetic vasodilator fibres emerge from the
      brain stem with the glossopharyngeal nerve and reach the blood vessels via the
      otic ganglion and the inferior alveolar nerve in the cat mandibular lip.

PMID- 1359121
TI  - Cholinergic excitation of GABAergic interneurons in the rat hippocampal slice.
AB  - 1. Intracellular recordings were made from CA1 pyramidal cells in the rat
      hippocampal slice to study the cholinergic modulation of GABAergic inhibition.
      The cholinergic receptor agonist, carbamylcholine (carbachol), depressed evoked
      excitatory postsynaptic potentials (EPSPs) and evoked inhibitory postsynaptic
      potentials (IPSPs), but enhanced small spontaneously occurring membrane potential
      fluctuations that resembled IPSPs. Both atropine (1 microM) and picrotoxin (25-60
      microM) abolished the small fluctuations. 2. Recording from cells with potassium
      or caesium chloride (KCl or CsCl)-filled microelectrodes enhanced and inverted
      spontaneous Cl(-)-dependent GABAA-mediated IPSPs. These events appeared to result
      from the spontaneous firing of GABAergic interneurons since they could be
      inhibited by picrotoxin or bicuculline and nearly eliminated by tetrodotoxin. 3.
      Muscarinic acetylcholine (ACh) receptor activation significantly increased the
      frequency of spontaneous-activity-dependent IPSPs from 1.7 +/- 0.4 s (mean +/-
      S.E.M.) in control saline to 7.0 +/- 1.1 s in carbachol (10-50 microM)-containing
      saline, although evoked IPSPs were inhibited. All effects of carbachol were
      completely reversed by atropine. 4. The increase in frequency of spontaneous
      IPSPs observed in carbachol was not secondary to changes in the postsynaptic cell
      and was not blocked by high doses of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX,
      5-10 microM) and 2-amino-5-phosphonovaleric acid (APV, 10-20 microM), which
      abolished evoked excitatory transmission. Amplitude histograms showed an increase
      in mean size as well as of frequency of spontaneous IPSCs in carbachol. 5.
      Stimulation of cholinergic afferents in stratum oriens in the presence of the
      acetylcholinesterase inhibitor eserine (1 microM) also increased spontaneous IPSP
      frequency, and the time course of this response was similar to that of the
      muscarinic slow EPSP. Postsynaptic factors or the activation of glutamatergic
      excitatory pathways could not account for this effect. 6. Evoked monosynaptic
      IPSCs in CNQX and APV were diminished by carbachol. 7. We conclude that GABAergic
      inhibitory interneurons possess muscarinic receptors, that activation of these
      receptors increases the excitability of the interneurons and that synaptically
      released ACh increases interneuronal activity. Cholinergic reduction of the
      monosynaptic IPSC may point to additional complexity in cholinergic regulation of
      the GABA system.

PMID- 1359123
TI  - Pharmacological and kinetic properties of alpha 4 beta 2 neuronal nicotinic
      acetylcholine receptors expressed in Xenopus oocytes.
AB  - 1. Co-injection of RNA synthesized from cloned neuronal acetylcholine receptor
      (nAChR) subunits (alpha 4 and beta 2) in Xenopus oocytes produced functional
      receptors. In macroscopic voltage-clamp experiments, the agonist-induced current
      exhibited a strong inward rectification. 2. Voltage jumps from +50 mV to more
      negative potentials produced relaxations of the agonist-induced current with a
      single exponential time course. The relaxation rate constant was only weakly
      voltage dependent. 3. At the single-channel level, three conductances were
      recorded of 12, 22 and 34 pS. Their burst durations were similar and varied only
      weakly with voltage (e-fold for 120 to 370 mV), consistent with the poorly
      voltage-dependent relaxation rate constants. However, the burst durations were
      less than 10 ms, or less than 1/5 the value expected from voltage-jump
      relaxations. 4. Hexamethonium (Hex, 0.5 to 8 microM) inhibited the agonist
      induced current and produced voltage-jump relaxations characterized by a rapid
      conductance increase and a slower conductance decrease. Analysis of these
      relaxations suggested that the Hex-receptor interaction is open-channel blockade
      characterized by a forward binding rate of 1 x 10(7) M-1 s-1 and a dissociation
      rate constant of about 25 s-1. 5. For the relaxations produced by QX222, the
      slowest phase was a conductance increase, suggesting that the dissociation rate
      constant for QX222 is 10-30-fold greater than for Hex. 6. Hex but not QX222
      produced an additional use-dependent blockade that was manifest during repetitive
      hyperpolarizing pulses. 7. With mouse muscle ACh receptors expressed in oocytes,
      the blockade by Hex did not depend strongly on voltage. Neither Hex nor QX222
      produced appreciable use-dependent block on muscle ACh receptors. 8. Of the four
      conditions studied (neuronal and muscle receptors, Hex and QX222), only the
      blockade of the neuronal AChR by Hex is characterized by a residence time longer
      than the normal open time. 9. It is concluded that the modest differences in
      primary amino acid sequence between muscle and neuronal receptors lead to
      profound changes in their interactions with channels blockers.

PMID- 1359124
TI  - Dopamine D2 receptor stimulation differentially affects voltage-activated calcium
      channels in rat pituitary melanotropic cells.
AB  - 1. Whole-cell voltage clamp recordings were made from 141 rat pituitary
      melanotropic cells in short-term, serum-free, primary culture. The effects of the
      dopamine D2 receptor agonist, LY 171555, on sodium, potassium and barium currents
      were investigated. 2. Application of 1 microM-LY 171555 did not affect the inward
      sodium and outward potassium currents. 3. Application of LY 171555 reversibly
      inhibited barium currents, with the strongest inhibition on the early inward
      current. The effect was dose dependent (IC50 = 4 x 10(-8) M), maximal inhibition
      of the total current was 30% and the LY 171555-induced block (1 microM) was
      reversibly antagonized by (+/-)sulpiride (4 microM). 4. Using barium-selective
      saline solutions, different types of barium current (T, N, and two L components)
      were identified on the basis of their voltage-dependent kinetics. Their relative
      amplitudes differed between cells. 5. The T-type current activated at potentials
      positive to -60 mV, reaching peak amplitude between -20 and -10 mV. At -30 mV,
      this current was inhibited up to 30% by 1 microM-LY 171555. The time constants of
      activation (10-3 ms) and inactivation (50-20 ms) as well as the voltage
      dependence of inactivation (potential of half-maximal inactivation (H), -61 mV;
      slope factor (S), 4.9 mV) were not affected by LY 171555 application. 6. A
      rapidly inactivating (time constants 100-50 ms), high threshold current component
      was identified as an N-type current. This current activated at command potentials
      positive to -30 mV and reached a maximal amplitude at +10 mV. The steady-state
      inactivation was described by a single Boltzmann equation with H = -65 mV and S =
      11.7 mV. Application of 1 microM-LY 171555 completely suppressed this current. 7.
      The slowly inactivating (time constants > 1500 ms), high-threshold, L-type
      current displayed the same voltage dependence of activation as the N current. The
      voltage dependence of inactivation was modelled by the sum of two Boltzmann
      equations (L1: H1 = -45 mV, S1 = 13.0 mV; L2:H2 = -11 mV, S2 = 6.0 mV),
      indicating the existence of two L channel populations. Neither time course, nor
      voltage dependence of inactivation were influenced by LY 171555. However, LY
      171555 induced a slow-down in the time course of activation, which necessitated
      the use of two time constants to model the activation kinetics. One of these
      (approximately 2 ms) was also observed under control conditions.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1359125
TI  - Quantal transmitter release mediated by strontium at the mouse motor nerve
      terminal.
AB  - 1. In isolated mouse diaphragm, nerve stimulation in the presence of Sr2+ evokes
      phasic quantal transmitter release (endplate potentials, EPPs) with the same time
      course as in the presence of Ca2+. 2. Brief tetanic trains of nerve stimuli in
      the presence of Sr2+ cause an increase in quantal content of EPPs accompanied by
      an increase in the frequency of miniature EPPs (MEPPs); the latter persists as a
      'tail' that subsides within about a second. Pseudo-random stimulation sequences
      were used to characterize these changes. 3. The fourth root of MEPP frequency
      during or after stimulation rose and fell in accordance with first order kinetics
      with the same time constants for rising and falling phases, in agreement with a
      'residual ion' model in which (a) each nerve impulse causes the same entry of
      Sr2+ into the nerve terminal, (b) transmitter release (MEPP frequency) is
      proportional to the fourth power of [Sr2+] at release sites, and (c) Sr2+ removal
      is a first order process with a time constant of about 250 ms. 4. After exposure
      to bis (O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, acetoxymethyl ester
      form (BAPTA AM), 'Sr2+ tails' of MEPP frequency were reduced in magnitude and
      prolonged. 5. During stimulation trains, growth of phasic transmitter release
      rates (and quantal content of EPPs) were related to growth of MEPP frequency in
      almost exact agreement with a residual ion model, in which 'phasic' release
      (EPPs) and MEPP frequency are governed by the same equation, with the same
      parameters, and without any effect of depolarization per se to affect phasic
      release. 6. Prolonged (1 s) nerve terminal depolarizations in the presence of
      Sr2+ produce increased MEPP frequency with a time course corresponding to a model
      in which depolarization per se has little or no effect to increase transmitter
      release. 7. It was concluded that in the presence of Sr2+ the intense 'phasic'
      acceleration of quantal release induced by nerve impulse manifest in an EPP can
      be attributed to a transient rise of intracellular [Sr2+] in the vicinity of
      release sites, while the modulation of 'phasic' release by antecedent nerve
      impulses can be attributed to residual Sr2+ which is also manifest in a rise in
      MEPP frequency.

PMID- 1359127
TI  - A procedure for modifying the occlusal surface of an all cast implant
      restoration.

PMID- 1359128
TI  - Glutamatergic motoneurons in the stomatogastric ganglion of the mantis shrimp
      Squilla oratoria.
AB  - 1. Transmitters of motoneurons in the stomatogastric ganglion (STG) of Squilla
      were identified by analyzing the excitatory neuromuscular properties of muscles
      in the posterior cardiac plate (pcp) and pyloric regions. 2. Bath and
      iontophoretic applications of glutamate produce depolarizations in these muscles.
      The pharmacological experiments and desensitization of the junctional receptors
      elucidate the glutamatergic nature of the excitatory junctional potentials (EJPs)
      evoked in the constrictor and dilator muscles. The reversal potentials for the
      excitatory junctional current (EJC) and for the glutamate-induced current are
      almost the same. 3. Some types of dilator muscle show sensitivity to both
      glutamate and acetylcholine (ACh) exogenously applied. The pharmacological
      evidence and desensitization of the junctional receptors indicate the
      glutamatergic nature of neuromuscular junctions in these dually sensitive
      muscles. The reversal potentials for the EJC and for the ACh-induced current are
      not identical. 4. Glutamate is a candidate as an excitatory neuro-transmitter at
      the neuromuscular junctions which the STG motoneurons named PCP, PY, PD, LA and
      VC make with the identified muscles. Kainic and quisqualic acids which act on
      glutamate receptors are potent excitants of these muscles. Extrajunctional
      receptors to ACh are present in two types of the muscle innervated by LA and VC.
      5. Neurotransmitters used by the STG motoneurons of stomatopods are compared to
      those of decapods.

PMID- 1359126
TI  - Activation and desensitization of N-methyl-D-aspartate receptors in nucleated
      outside-out patches from mouse neurones.
AB  - 1. Activation and desensitization of N-methyl-D-aspartate (NMDA) receptors were
      studied in large outside-out patches excised from cultured embryonic neurones
      dissociated from mouse forebrain. The patches were exposed to rapid changes of
      NMDA or L-glutamate concentrations in the presence of glycine at concentrations
      (10-20 microM) saturating the modulatory site of the NMDA receptor. 2.
      Immediately after formation of the patch the responses to NMDA and L-glutamate
      showed a slow and small desensitization, even with high concentrations of
      agonist. During the following hour, the peak response either decreased or
      remained relatively stable, but in all cases the desensitization increased and
      accelerated until it stabilized. In this 'stabilized' state, the desensitization
      produced by high concentrations of NMDA (1 mM) or L-glutamate (300 microM) had an
      exponential time course, with a time constant of about 30 ms. The ratio of the
      peak over the steady-state current was in the order of 40 for NMDA and about 30
      for L-glutamate. 3. Concentration-response curves were built for the peak and the
      plateau responses, for NMDA and for L-glutamate. The comparison of these curves
      indicated that (i) the EC50 of the peak (K(app) was always higher than the EC50
      of the plateau (Kss); (ii) the two EC50 values for NMDA (K(app) and Kss) were
      higher than those for L-glutamate; (iii) the Hill coefficient was close to 1.4
      for each of the four curves. 4. The application of NMDA or L-glutamate at a low
      concentration for 3 s periods reduced the response to a subsequent application of
      the same agonist at a saturating concentration. The IC50 of this
      'predesensitization', termed Kpre, was lower than the EC50 of the steady-state
      response, Kss. 5. The onset rates of desensitization increased with the
      concentration of agonist. The EC50 of this relation was close to the value of
      K(app). 6. The decay of the currents at the end of a 3 s application of agonist
      was usually well described by the sum of two exponentials both of which were
      faster for NMDA than for L-glutamate. 7. The recovery from desensitization after
      a long (3 s) pulse of agonist was approximately exponential, with a time constant
      of about 0.5 s for NMDA and about 3.5 s for L-glutamate.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1359129
TI  - The morphology, innervation and neural control of the anterior arterial system of
      Aplysia californica.
AB  - The morphology, innervation, and neural control of the anterior arterial system
      of Aplysia californica were investigated. Immunocytochemical and histochemical
      techniques generated positive reactions in the anterior arterial system for
      several neuroactive substances, including SCPB, FMRFamide, R15 alpha 1 peptide,
      dopamine and serotonin. Three neurons were found to innervate the rostral
      portions of the anterior arterial tree. One is the identified peptidergic neuron
      R15 in the abdominal ganglion, and the other two are a pair of previously
      unidentified neurons, one in each pedal ganglion, named pedal arterial shorteners
      (PAS). The endogeneously bursting neuron R15 was found to innervate the proximal
      anterior aorta. It also innervates a branch of the distal anterior aorta, the
      left pedal-parapodial artery. Activity in R15 causes constriction of the left
      pedal-parapodial artery. This effect is presumed to direct hemolymph towards the
      genital groove and penis on the right side in vivo. This vasoconstrictor action
      of R15 is mimicked by the R15 alpha 1 peptide. The PAS neuron pair causes
      longitudinal contraction of the rostral anterior aorta and the pedal-parapodial
      arteries. In vivo, the pair is active during behaviors involving head withdrawal
      and turning. By adjusting the length of the arteries during postural changes, the
      PAS neurons may prevent disturbances in blood flow due to bending or kinking of
      the arterial walls.

PMID- 1359130
TI  - Local research ethics committees. Report of the 2nd National Conference.
AB  - The major theme of this conference was the present variable performance of local
      research ethics committees (LRECs). Opening the meeting, Dame Margaret Turner
      Warwick pointed to the tremendous advances that were taking place in medical
      practice and science and that this was therefore an opportune moment to 'see
      where we are, and share solutions as well as problems in the discussion and
      debate of this meeting'.

PMID- 1359131
TI  - Who will care for our elderly people?
AB  - A conference on the topic 'Who will care for our elderly people?' was held at the
      Royal College of Physicians on 16 March 1992. It began with a consideration of
      the challenge in terms of numbers and problems.

PMID- 1359132
TI  - General medicine and ophthalmology: common interests.
AB  - A conference entitled 'General Medicine and Ophthalmology' was held at the Royal
      College of Physicians on 1 June, 1992. Eye diseases are frequently a
      manifestation of systemic conditions; it is therefore in the patient's best
      interest for ophthalmologists and physicians to co-operate in their management.
      Without such co-operation there is the risk that patients fall between stools and
      neither condition is adequately treated. Medical specialties in which eye
      conditions are particularly prominent include dermatology, endocrinology,
      neurology, rheumatology, and cardiovascular diseases. The advantages of joint
      clinics in medicine and ophthalmology were demonstrated by Professors Alex
      Crombie and Pat Kendall-Taylor for Graves' disease, by Mr Philip Murray and Dr
      David Young for uveitis, and by Professor Eva Kohner for diabetes. These included
      more expert assessments of patients leading to quicker and more complete
      diagnoses, earlier recognition of complications, and access to a wider range of
      investigations and treatments, opportunities for collaborative research, improved
      education for patients and doctors, increased patient convenience, and a stimulus
      for better control of factors which can worsen the disease.

PMID- 1359133
TI  - Treatment and prevention of falciparum malaria in Africa.

PMID- 1359134
TI  - Effect of a histamine H2 type receptor antagonist (WY 45, 727) on the healing of
      gastric ulcers in ponies.
AB  - Using video gastroscopy, the efficacy of a Histamine-H2 type receptor antagonist
      (WY 45, 727) was investigated in young ponies with spontaneous and experimentally
      induced gastric ulcers. Oral administration of WY 45, 727 at 2 mg/kg and 10 mg/kg
      of body weight every 12 hours for 14 days resulted in complete healing of
      spontaneous gastric ulcers in the non-glandular portion of the stomach in 2/5
      (40%) and 3/4 (75%) of the ponies, respectively, compared (P < 0.05) to 0/5 (0%)
      placebo-treated ponies. After intramuscular administration of flunixin meglumine
      at 1.5 mg/kg body weight every 8 hours for 6 days, 9/18 ponies had ulcers in the
      non-glandular portion of the stomach. Oral administration of WY 45, 727 at 10
      mg/kg body weight every 12 hours for 14 days resulted in complete healing of the
      non-glandular gastric ulcers in 3/4 (75%) compared with (P < 0.05) 1/5 (20%)
      placebo-treated ponies. This study indicates that 1) the occurrence of
      subclinical ulcers may be common in young ponies; 2) flunixin meglumine at 1.5
      mg/kg intramuscularly every 8 hours for 6 days may result in ulcers of the non
      glandular stomach in ponies; and 3) WY 45, 727, a histaminergic H2 type receptor
      antagonist could be of value in the therapeutic management of ulcers in the non
      glandular stomach of foals and adult horses.

PMID- 1359135
TI  - FDA and ADA Evaluation of Dental Products: Implications for Dentists and their
      Patients. Symposium proceedings. Baltimore, Maryland, October 25-26, 1991.

PMID- 1359136
TI  - Immunohistochemical localization of 3 beta-hydroxysteroid/delta 5-delta 4
      isomerase, tyrosine hydroxylase and phenylethanolamine N-methyl transferase in
      adrenal glands of sheep fetuses throughout gestation and in neonates.
AB  - Immunoreactive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3
      beta-HSD) was localized in adrenal glands of sheep fetuses in cortical-type
      cells, but not in medullary-type cells, from day 43 of gestation to term and in 2
      4-day-old neonates. From day 54 of gestation, the formation of distinct zones
      within the adrenal cortex was apparent and immunoreactive 3 beta-HSD was found in
      cortical cells in the zona fasciculata and in groups and cords of cortical cells
      within the developing medulla, with weak positive staining in the zona
      glomerulosa. At this stage, most medullary cells were positive for immunoreactive
      tyrosine hydroxylase, and some of these cells with a juxtacortical distribution
      also stained positively for immunoreactive phenylethanolamine N-methyl
      transferase (PNMT). Between days 65 and 130, the adrenal medulla increased in
      size with little change in the width of the cortex. Organization and zonation of
      immunoreactive 3 beta-HSD staining cells were evident in the zona fasciculata and
      in groups of cells in the medulla. Between day 130 and term, uniform
      immunoreactive 3 beta-HSD staining was found throughout the zona fasciculata, and
      there was also staining in single cells and small clusters of cells throughout
      the medulla. At this stage, immunoreactive tyrosine hydroxylase was distributed
      in most cells throughout the medulla, but in two distinct patterns: cells
      staining intensely for immunoreactive tyrosine hydroxylase in the central region
      of the medulla, and cells exhibiting weaker staining for immunoreactive tyrosine
      hydroxylase localized in a juxta-cortical position. These juxta-cortical cells
      were also positive for immunoreactive PNMT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359137
TI  - Neuroleptic-associated hyperprolactinemia. Can it be treated with bromocriptine?
AB  - Six stable psychiatric outpatients with hyperprolactinemia and
      amenorrhea/oligomenorrhea associated with their neuroleptic medications were
      treated with bromocriptine. Daily dosages of 5-10 mg corrected the
      hyperprolactinemia and restored menstruation in four of the six patients. One
      woman, however, developed worsened psychiatric symptoms while taking
      bromocriptine, and it was discontinued. Thus, three of six patients had their
      menstrual irregularity successfully corrected with bromocriptine. This suggests
      that bromocriptine should be further evaluated as potential therapy for
      neuroleptic-associated hyperprolactinemia and amenorrhea/galactorrhea.

PMID- 1359138
TI  - Human T cell leukemia virus-I carriers and gonarthrosis. A preliminary report.
AB  - Gonarthrosis in 11 human T cell leukemia virus-1 (HTLV-I) carriers were studied
      for sera, synovial fluids (SF) and cerebrospinal fluids (CSF). Atypical
      lymphocytes similar to adult T cell leukemia cells were noticed in the SF of all
      the HTLV-I carriers and ranged from 19 to 1%, while those of peripheral white
      blood cells ranged from 3 to 0%. Anti-HTLV-I antibodies in the SF were equal to
      or lower than those in the sera. The CSF from 7 of them demonstrated positive
      titers of anti-HTLV-I antibodies, while no evidence of neurological disorders
      manifested. The histopathological findings of synovial membranes on hematoxylin
      and eosin staining method showed no statistical difference between those of
      gonarthrosis of HTLV-I carriers and noncarriers.

PMID- 1359139
TI  - Long-term effects on insulin sensitivity and sodium transport in glucose
      intolerant hypertensive subjects when beta-blockade is replaced by captopril
      treatment.
AB  - Long-term effects on insulin sensitivity and leucocyte sodium transport were
      studied in 42 glucose-intolerant hypertensives on beta-blockers, randomly
      assigned to continuous beta-blockade (beta group) or a switch to captopril
      treatment (mean daily dose 69.1 mg) (ACE group). In the ACE group, despite a
      tendency towards improvement, glucose uptake during the euglycaemic insulin clamp
      procedure did not change significantly from the baseline value of 4.0(0.5-12.9)
      mg/kg/min, values at 6 and 12 months being 4.8(1.3-14.7) and 4.4(1.5-9.8)
      mg/kg/min, respectively: the corresponding values for the beta group were 4.2(1.1
      15.3), 3.6(1.2-8.9) and 4.0(1.5-12.0) mg/kg/min. The 22Na efflux rate constant,
      both baseline and follow-up values, was similar in both groups, and unrelated to
      insulin sensitivity. Owing to the surprisingly great variation in peripheral
      glucose uptake, the subgroup with values below the median for the population as a
      whole (4.9 mg/kg/min) was evaluated separately: those switched to captopril
      treatment manifested a 60% improvement in glucose disposal at 6 months and
      persisting at 12 months, the respective values being 2.1(0.5-4.8) (baseline),
      3.5(1.3-6.3) and 3.4(1.5-6.1) mg/kg/min, (P = 0.012). The body mass index (BMI)
      was not significantly affected. Values for BMI, peripheral insulin and
      triglycerides were higher in the subgroup with glucose disposal below the median
      than in the subgroup with values above the median. Correlation between BMI and
      glucose uptake was highly significant (r = -0.75, P = 0.0001). The present
      findings suggest that captopril may be a better alternative than beta-blockers
      for treating the highly insulin-resistant, glucose-intolerant patients,
      predominantly to be found among the overweight.

PMID- 1359140
TI  - Influence of mild to moderate treated hypertension on 9-11 year mortality in
      patients with pre-existing coronary heart disease.
AB  - Hypertension is a known risk factor in the genesis of coronary artery disease.
      However, the effect of pre-existing hypertension on the long-term mortality in
      patients with established coronary heart disease is not clear. The present cohort
      study analysed the influence of baseline mild to moderate treated hypertension in
      cases of known coronary heart disease with cardiac mortality as end point. Data
      from a cohort of 511 patients including 266 normotensives and 245 controlled
      hypertensives was analysed over a follow-up period of 9 to 11 years. The baseline
      data were identical regarding other major risk factors like age, gender, smoking,
      diabetes, cholesterol levels and congestive heart failure on univariate analysis.
      There were more cases of myocardial infarction in the normotensive group. The
      number of patients receiving beta-blockers or aspirin were similar in both
      groups. However, more patients in the hypertensive group received nifedipine.
      Actuarial analysis of survival showed that mortality was the same in both groups
      with an overall cardiac mortality of 65 (26.5%) in the hypertensive group and 86
      (32.3%) in the normotensive group (P greater than 0.1). The survival curves also
      showed no significant difference in mortality at any point in time (logrank test
      = 2.37, P greater than 0.1). Analysis of mortality after adjusting for myocardial
      infarction at first presentation also showed no significant difference. These
      data indicate that in patients with coronary heart disease the presence of mild
      to moderate hypertension does not add to the risk of cardiac mortality.

PMID- 1359141
TI  - Synthesis and hypoglycemic activity of substituted 8-(1-piperazinyl)imidazo[1,2
      a]pyrazines.
AB  - A series of alkyl- and halo-substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines
      were prepared using two approaches, the condensation of alpha-halocarbonyl
      derivatives with an aminopyrazine or the oxidation-dehydration of a [(beta
      hydroxyalkyl)amino]pyrazine. These imidazo[1,2-a]pyrazines were evaluated for
      their binding affinity to the alpha 1, alpha 2, beta 1, and beta 2 adrenergic
      receptors as well as their ability to lower blood glucose in insulin resistant
      hyperglycemic ob/ob mice. Modifications on 8-(1-piperazinyl)imidazo[1,2
      a]pyrazine (4) reduced alpha 2 binding, lowered hypoglycemic potency, and showed
      variations in binding to the alpha 1, beta 1, and beta 2 adrenergic receptors. In
      addition to 4, the 2-methyl, 3-methyl, and 5-methyl 8-(1-piperazinyl)imidazo[1,2
      a]pyrazines (16k, 25m, and 16f, respectively) displayed high affinity for the
      alpha 2 receptor and were potent hypoglycemic agents when compared to 2-amino-7,8
      dihydro-4-(1-piperazinyl)-6H-thiopyrano[3,2- d]pyrimidine (MTP-1403, 2). Receptor
      binding was modified by use of a 4-methylpiperazine moiety which reduced alpha 1
      and beta 1 binding while retaining some hypoglycemic activity. The structure
      activity relationship for heterocyclic alkyl and halo substitution on biological
      activity is discussed.

PMID- 1359142
TI  - Synthesis and dopaminergic activity of some 3-(1,2,3,6-tetrahydro-1
      pyridylalkyl)indoles. A novel conformational model to explain structure-activity
      relationships.
AB  - The synthesis and dopaminergic properties of a novel type of dopamine agonist is
      described. The number and kind of essential structural elements differ
      significantly from that of the rigid apomorphine-type dopamine agonists. Using
      standard molecular modeling techniques, a conformational model is developed
      proposing a U-shaped conformation which might be energetically preferred through
      aromatic pi-pi-interactions between both of the electron rich aromatic structural
      elements of this class of compounds. Superimposition of conformations of the lead
      compound 28 with apomorphine yields a novel model explaining the atypical
      structure-activity relationships found in this class of indolealkylamines.

PMID- 1359143
TI  - Synthesis of biologically active taxol analogues with modified phenylisoserine
      side chains.
AB  - Taxol (1) is a highly potent antitumor agent, exerting its mechanism of action by
      promoting the assembly of stable microtubules in cells. We are reporting on the
      first synthesis and biological evaluation of taxol derivatives with substituted
      phenyl rings at the C-13 N-benzoyl-(2'R,3'S)-3'-phenylisoserine side chain of
      taxol (1). Two taxol derivatives were synthesized, one possessing a N-(p
      chlorobenzoyl)-(2'R,3'S)-3'-phenylisoserine side chain (2) and the other one a N
      benzoyl-(2'R,3'S)-3'-(p-chlorophenyl)isoserine side chain (3). The synthesis of
      the novel phenylisoserine side chains was achieved through the asymmetric
      synthesis of 3-hydroxy-4-aryl-2-azetidinone derivatives via the ester enolate
      imine cyclocondensation reaction. The 2-azetidinones 14 and 15 were acylated with
      p-chlorobenzoyl chloride and benzoyl chloride, respectively, to form the N-acyl
      beta-lactams 16 and 17. Subsequent coupling of 16 and 17 to 7
      (triethylsilyl)baccatin III (6) in the presence of pyridine and DMAP afforded,
      after removal of the protecting groups, the desired taxol analogues 2 and 3 in
      excellent yields. The newly synthesized derivatives 2 and 3 were tested in the
      tubulin assembly assay and also evaluated for their cytotoxicity against B16
      melanoma cells. It was found that the taxol derivatives 2 and 3 had activity
      comparable to taxol (1).

PMID- 1359145
TI  - Difficult diagnosis of the fragile X syndrome made possible by direct detection
      of DNA mutations.
AB  - Genetic recombination near the fragile X locus (Xq27.3) has frequently been a
      problem in linkage studies of families in which the fragile X is segregating.
      This case report illustrates the resolution of a difficult situation in a fragile
      X family for whom cytogenetic studies were inconclusive and where recombination
      had twice confounded attempts at prenatal DNA diagnosis by RFLP analysis. Using a
      newly developed DNA probe, StB12.3, for direct detection of DNA instability in
      the fragile X locus, the presence of the fragile X was ascertained definitively
      in a prenatal DNA sample.

PMID- 1359144
TI  - Large de novo DNA deletion in a patient with sporadic neurofibromatosis 1, mental
      retardation, and dysmorphism.
AB  - A mildly dysmorphic, mentally retarded male with neurofibromatosis 1 (NF1) was
      found to have a de novo deletion of chromosome 17. The deletion occurred on the
      paternally derived chromosome 17 as shown by the absence of a D17S73 paternal
      allele. Densitometric analysis indicated that, in addition to the D17S73 locus,
      the patient has only one copy of four other adjacent loci. The deletion involved
      the loci D17S120, NF1, D17S57, D17S115, and D17S73 and was estimated to encompass
      more than 380 kb of DNA. The deletion of the entire paternal NF1 allele argues
      strongly that this disorder is not caused by the action of an abnormal NF1
      protein. The extent of the deletion suggests that the mental retardation and
      dysmorphism of this patient may result from a deletion involving both the NF1
      gene and contiguous genetic material.

PMID- 1359146
TI  - Report of ENMC workshop on the limb-girdle muscular dystrophies.

PMID- 1359147
TI  - The adherence of verocytotoxin-producing Escherichia coli to rabbit intestinal
      cells.
AB  - Verocytotoxin-producing Escherichia coli (VTEC) have been recognised recently as
      an important cause of human disease. The adherence of VTEC to rabbit intestinal
      tract and the relationship between adherence and other virulence traits were
      studied. Twenty clinical isolates of VTEC (O157:H7 and other serotypes) and a
      control, commensal E. coli strain, were examined. Bacteria were evaluated for the
      presence of surface fimbriae, plasmid profile and hybridisation with a 3.4 kb DNA
      probe derived from the 60-MDa plasmid of such strains. Adherence was determined
      by electronmicroscopy and quantitatively with radio-labelled bacteria. Of the
      VTEC strains, 12 (60%) had surface fimbriae; all O157:H7 and 10 (70%) of 14 of
      the non-O157:H7 strains hybridised with the probe. No isolate was negative for
      both of these virulence traits and there was no correlation between their
      presence. The plasmid profiles varied among the strains, with no correlation to
      virulence traits. The adherence of VTEC strains differed significantly, ranging
      from 0.3 to 34.0 bacteria/intestinal cell. The mean adherence of fimbriate
      strains was greater than that of non-fimbriate strains (3.9 versus 2.7
      bacteria/cell), although marked variability was noted in both groups. This study
      showed that VTEC strains differed markedly in their adherence capability and that
      neither the presence of fimbriae nor hybridisation with the 3.4-kb probe was
      essential for adherence. Several distinct mechanisms probably play a role in VTEC
      adherence.

PMID- 1359148
TI  - Variation in the CD4+ and CD8+ populations in lymph nodes does not reflect that
      in the blood during SIVMNE/E11S infection of macaques.
AB  - The decline in the CD4% and CD4/CD8 ratios have been compared in lymph nodes and
      blood from SIVMNE/E11S infected rhesus macaques. The results indicate that loss
      from the LN CD4+ cell pool does not occur until CD4/CD8 ratios of less than 0.5
      is reached in blood. These changes also correlate with the ability to isolate
      virus from the blood and the transition of CD45RAhi to highly activated CD45RAlo
      CD8+ cells both of which may play a role in eliminating CD4+ cells. In end-stage
      disease, CD8+ cells also decline in LN and mitogen responsiveness no longer
      exists in any nodes. Interestingly at this stage, the circulating CD8% increases
      significantly and represents the only source of functional T cells remaining in
      the body.

PMID- 1359150
TI  - MDR1 (P-glycoprotein) gene expression--implications for resistance modifier
      trials.

PMID- 1359149
TI  - Correlates of SIV encephalitis in rhesus monkeys.
AB  - Necropsy records from 204 SIV-infected rhesus monkeys that had been inoculated
      with various strains of SIV and had died of SIV-related disease were reviewed.
      The relationship of SIV encephalitis with other parameters was evaluated.
      Encephalitis was associated with the presence of syncytial cells in other
      tissues, with persistent or early recurrent antigenemia, with a selective
      decrease in CD4+CD29+ blood lymphocytes, and with a shortened time of survival.
      Monkeys whose lymphocytes produced high levels of virus in culture also had a
      higher incidence of encephalitis. SIV was more frequently isolated from the
      brains of animals with encephalitis. No other clear associations were detected.

PMID- 1359151
TI  - More patients to receive taxol.

PMID- 1359152
TI  - Clinical correlates of MDR1 (P-glycoprotein) gene expression in ovarian and small
      cell lung carcinomas.
AB  - BACKGROUND: Expression of the MDR1 (P-glycoprotein) gene causes resistance to
      several classes of lipophilic anti-cancer drugs, but MDR1 expression in untreated
      ovarian and lung carcinomas is rarely detectable by standard assays. PURPOSE:
      This study was designed to measure the MDR1 messenger RNA (mRNA) content of
      ovarian and lung carcinomas and to analyze clinical correlations of MDR1
      expression in these tumors. METHODS: A sensitive assay based on the polymerase
      chain reaction (PCR) was used in a retrospective study to measure MDR1 mRNA in
      biopsy samples of 100 solid tumors, including 60 ovarian and 32 lung carcinomas.
      The levels of MDR1 mRNA were correlated with history of chemotherapeutic
      treatment for all tumors; for ovarian and small-cell lung carcinomas (SCLCs),
      these levels were also correlated with subsequent tumor response to chemotherapy.
      RESULTS: Among previously untreated patients, MDR1 mRNA was expressed in 68% (50
      of 74) of all tumors. Among patients pretreated with chemotherapy regimens that
      included at least one P-glycoprotein-transported drug (MDR regimens), 95% (20 of
      21) of all tumors expressed MDR1 mRNA though the incidence of high-level MDR1
      expression was decreased among the treated tumors. MDR1 mRNA was expressed in
      only one of five tumors treated with regimens that included no P-glycoprotein
      substrates (non-MDR regimens). Subsequent tumor response to chemotherapy was
      evaluated in 35 patients with ovarian carcinoma and seven patients with SCLC. The
      presence of even very low levels of MDR1 mRNA correlated with the lack of
      response to MDR regimens in these tumor types (P < .035 for ovarian carcinomas, P
      < .029 for SCLCs, and P < .0005 for both tumor types; Fisher's Exact Test).
      CONCLUSIONS: Low-level expression of MDR1 mRNA correlates with clinical
      resistance to combination chemotherapy in ovarian cancer and SCLC. We hypothesize
      that MDR1 is expressed in a subpopulation of more malignant tumor cells
      possessing multiple mechanisms of drug resistance. IMPLICATIONS: The presence of
      MDR1-expressing tumor cells may be useful as a predictive marker for clinical
      resistance to combination chemotherapy in ovarian cancer and SCLC. Prospective
      studies are needed to confirm this hypothesis.

PMID- 1359153
TI  - Effect of P-glycoprotein expression on sensitivity to hormones in MCF-7 human
      breast cancer cells.
AB  - BACKGROUND: Data obtained from studies of primary human breast cancers and
      established cell lines indicate that overexpression of the MDR1 gene (also known
      as PGY1) is associated with decreased expression of steroid hormone receptors and
      increased expression of epidermal growth factor (EGF) receptors. Other study
      results indicate that both progestins and triphenylethylene antiestrogens may be
      substrates for P-glycoprotein, the product of the MDR1 gene. These findings
      together suggest an association between overexpression of the MDR1 gene and cross
      resistance to progestin and antiestrogen therapies. PURPOSE: This study was
      designed to determine (a) the ability of MDR1 expression to alter tumor
      sensitivity to hormone therapy and (b) the role of MDR1 expression in expression
      of functional hormone receptors in human breast cancer. METHODS: We transduced
      MCF-7 cells with MDR1 complementary DNA, using a retroviral vector directing the
      constitutive expression of the MDR1 gene. Transduced cells (MCF-7MDR1) were
      examined for ability to produce P-glycoprotein, expression of steroid hormone
      receptors, and responsivity to antiestrogens. For comparison, we used MCF-7ADR
      human breast cancer cells, which overexpress MDR1 and have also lost the
      requirement for 17 beta-estradiol supplementation to form tumors in nude mice. We
      also investigated the level of EGF-R mRNA expression by using a sensitive RNase
      protection analysis. RESULTS: MCF-7MDR1 cells retained both estrogen receptor and
      progesterone receptor expression as well as sensitivity to 4-hydroxytamoxifen.
      Expression of the estrogen-inducible pS2 and EGF receptor genes was similar in
      parental MCF-7 and transduced MCF-7MDR1 cells. EGF receptor expression was
      increased, and pS2 expression was lost (undetectable) in MCF-7ADR cells.
      CONCLUSIONS: The data indicate that overexpression of the MDR1 gene alone confers
      a multidrug-resistant phenotype, but it does not directly result in either cross
      resistance to antiestrogens or a loss of steroid hormone receptor expression.
      IMPLICATIONS: MCF-7MDR1 cells provide an important model for study of the
      interactions of cytotoxic drugs, hormones, and the MDR1 glycoprotein in human
      hormone-responsive breast cancer cells.

PMID- 1359154
TI  - Phase I trial of Taxotere: five-day schedule.
AB  - BACKGROUND: Taxotere, a semisynthetic compound structurally related to taxol, has
      a broad spectrum of activity in murine transplantable tumors; in the B16 melanoma
      model, it caused a total log cell kill 2.5 times greater than that caused by
      taxol at equitoxic doses. PURPOSE: We conducted a phase I study of Taxotere (a)
      to determine its qualitative and quantitative toxic effects and a starting dose
      for phase II trials, (b) to investigate its clinical pharmacology, and (c) to
      document its antitumor activity. METHODS: Taxotere was given as a 1-hour infusion
      at a starting dose of 1 mg/m2 per day for 5 consecutive days. The 5-day course of
      therapy was repeated every 21 days. Thirty-nine cancer patients with advanced
      disease were entered in the study; at least three patients were entered at each
      dose level. Initial dose escalations were planned at 100% increments until
      biologic activity was observed; subsequent escalations were planned at 50%
      increments until grade 2 toxicity (the National Cancer Institute's Common
      Toxicity Criteria) occurred and then at 25% increments until the maximum
      tolerated dose was established. RESULTS: Thirty-nine patients were entered in the
      study. Successive dose levels used were 1, 4, 8, 16, 12, and 14 mg/m2 per day.
      The dose-limiting toxic effects were granulocytopenia and concurrent mucositis.
      Grade 4 granulocytopenia associated with grade 3 mucositis developed in six of 12
      patients treated at a dose of 16 mg/m2 per day, two of 10 treated at 12 mg/m2 per
      day, and two of eight treated at 14 mg/m2 per day. Because these toxic effects
      occurred concurrently, all patients so affected developed neutropenic fevers and
      required hospitalization. Neither cardiac nor neurologic toxic effects were
      noted. Anti-tumor activity was observed in six patients with ovarian cancer and
      in one with breast carcinoma. Although pharmacokinetic parameters were consistent
      between day 1 and day 5 for individual patients, considerable variation existed
      among those treated at the same dose level. A relationship was observed between
      the area under the curve for plasma concentration of drug x time (AUC) on day 1
      and the percentage decrease in absolute granulocyte counts. CONCLUSION:
      Granulocytopenia associated with oral mucositis is the dose-limiting toxicity of
      this schedule. We recommended a starting dose of 14 mg/m2 per day for phase II
      studies of this 5-day schedule. Dose modifications on days 2-5 based on the day-1
      AUC may allow individualized dosing.

PMID- 1359155
TI  - High-dose oral tamoxifen, a potential multidrug-resistance-reversal agent: phase
      I trial in combination with vinblastine.
AB  - BACKGROUND: P-glycoprotein mediates resistance to natural-product anti-neoplastic
      agents like vinblastine through an active transport process resulting in reduced
      intracellular concentration of these agents. The triphenylethylene antiestrogen
      tamoxifen and its major metabolite N-desmethyltamoxifen at concentrations of 4-6
      microM enhance the intracellular concentration of natural-product antineoplastics
      and augment the cytotoxicity of such drugs three-fold to 10-fold in a variety of
      human and murine cell lines. PURPOSE: On the basis of these preclinical findings,
      we conducted a phase I clinical trial of high-dose, oral tamoxifen administered
      in conjunction with a 5-day continuous infusion of vinblastine. METHODS: We
      studied 53 patients with advanced epithelial tumors. Tamoxifen was given orally
      as a loading dose on day 1, followed by two doses a day on days 2-13. Vinblastine
      was given as a 120-hour continuous infusion (1.5 mg/m2 per day) on days 9-13 of
      each tamoxifen course. The starting dose of tamoxifen was 40 mg/m2 administered
      twice a day following a loading dose of 150 mg/m2. The maximum dose was 260 mg/m2
      twice a day following a loading dose of 680 mg/m2. Treatment cycles were repeated
      every 28 days. RESULTS: The dose-limiting toxic effects of tamoxifen were
      neurologic and began within 3-5 days after the start of treatment. They consisted
      of tremor, hyperreflexia, dysmetria, unsteady gait, and dizziness. One patient
      experienced a grand mal seizure 24 hours after the last tamoxifen dose. Toxic
      effects were rapidly reversible. Asymptomatic prolongation of the QT interval on
      electrocardiogram occurred at doses of tamoxifen of 80 mg/m2 or higher given
      twice a day. No coagulation or ophthalmologic abnormalities occurred. Tamoxifen
      did not enhance the toxicity of vinblastine. Mean plasma concentrations of
      tamoxifen or N-desmethyltamoxifen at 260 mg/m2 tamoxifen given twice a day for 13
      days were 6.04 and 6.56 microM, respectively. There was no relationship between
      plasma antiestrogen content and the development of neurotoxic effects.
      CONCLUSIONS: Tamoxifen at 150 mg/m2 given twice a day following a loading dose of
      400 mg/m2 results in plasma levels of tamoxifen and N-desmethyltamoxifen of 4 and
      6 microM, respectively, without dose-limiting toxicity. We recommend this dose
      for phase II trials of tamoxifen to modulate P-glycoprotein-mediated drug
      resistance. IMPLICATIONS: Our study demonstrates that high-dose tamoxifen can be
      safely administered and that plasma concentrations that may inhibit P
      glycoprotein function can be achieved.

PMID- 1359156
TI  - Phase II studies: untreated breast cancer patients.

PMID- 1359157
TI  - Relationship among prognostic laboratory indices in breast cancers.

PMID- 1359158
TI  - In vitro and in vivo inhibition of lysyl oxidase by aminopropionitriles.
AB  - Inhibition of lysyl oxidase (protein-lysine 6-oxidase, EC 1.4.3.13) decreases the
      rate of collagen and elastin cross-link formation and produces osteolathyrism in
      animals. Organic nitriles, including beta-aminopropionitrile (BAPN), have been
      shown to irreversibly inhibit lysyl oxidase in vitro. Both BAPN and 3,3'
      iminodipropionitrile (IDPN) have been shown to produce osteolathyric changes when
      administered to animals. To date compounds that have been reported to inhibit
      this enzyme possess a primary amine functional group. In this study a series of
      primary and substituted aminopropionitriles was studied for their ability to
      inhibit lysyl oxidase activity both in vitro and in vivo. Our results show that
      of the compounds tested, BAPN was the most potent inhibitor of the enzyme.
      Reversible inhibition of lysyl oxidase in vitro was found with two secondary
      aminonitriles, IDPN and monomethylaminopropionitrile (MMAPN). There was no
      inhibition of enzyme activity associated with the tertiary compound 3,3'
      dimethylaminopropionitrile (DMAPN) or propionitrile, a compound lacking an amine
      functional group. IDPN was found to produce a slight irreversible inhibition of
      the enzyme both in vitro and in vivo. Pretreatment of rats with pargyline, an
      inhibitor of monoamine oxidase, was found to increase the inhibitory potential of
      BAPN (p < or = .1). Pargyline pretreatment did not alter the inhibitory potential
      for any of the other aminonitriles tested. These results suggest that the
      presence of a primary amino functional group is not a strict requirement for
      inhibition of lysyl oxidase. In addition, reversible and irreversible mechanisms
      of inhibition may be involved in the production of osteolathyric changes
      associated with IDPN exposure.

PMID- 1359159
TI  - Phenotypic plasticity of avian embryonic sympathetic neurons grown in a
      chemically defined medium: direct evidence for noradrenergic and cholinergic
      properties in the same neurons.
AB  - Avian embryonic sympathetic ganglia possess both catecholaminergic and
      cholinergic features and can synthesize noradrenaline (NAd) and acetylcholine
      (ACh) simultaneously. In the present study we sought to determine (1) whether or
      not this coproduction of NAd and ACh corresponds to the existence of two non
      overlapping populations, and (2) to what extent the levels of synthesis are
      influenced by non-neuronal ganglion cells. We have focused on the correlation
      between the immunocytochemically demonstrable presence of the noradrenergic and
      cholinergic enzymes tyrosine hydroxylase (TH) and choline acetyltransferase
      (ChAT), respectively, and the synthesis of the corresponding neurotransmitters in
      embryonic quail sympathetic neuronal and non-neuronal cells purified by
      fluorescence-activated cell sorting. We show that (1) freshly sorted neurons
      synthesize both NAd and ACh, whereas non-neuronal cells produce neither; (2) the
      overwhelming majority of the sympathetic neurons display TH immunoreactivity; (3)
      about half of the TH-positive neurons are recognized by an anti-ChAT antibody in
      an artificial medium that selectively enhances synthesis and/or accumulation of
      ACh; (4) the non-neuronal cells are important for survival of the neurons and
      potentiate their synthesis of ACh in this medium, and (5) finally, we present
      evidence that expression of TH in noradrenergic neurons and in small intensely
      fluorescent cells of sympathetic ganglia is differentially regulated.

PMID- 1359160
TI  - Clinical evaluation of pediatric ethylene glycol monobutyl ether poisonings.
AB  - Ethylene glycol butyl ether, CAS 111-76-2, an ingredient in many popular
      commercial window/glass cleaners, is known to produce equal if not greater
      toxicity than ethylene glycol when administered to animals. Treatment
      recommendations for human poisonings are based upon animal data and include the
      use of ethanol therapy to inhibit the production of toxic metabolites. No human
      experiential data exist to accurately assess human toxicity or to verify
      treatment modalities. A 5 month retrospective review of all glass cleaner
      ingestions reported to a regional poison information center disclosed 24
      pediatric patients, ages 7 mo to 9 y, who ingested 5-300 mL of a liquid glass
      cleaning product containing ethylene glycol butyl ether. All ingestions were
      reported within 5 min of ingestion, and all 24 children were asymptomatic at that
      time and subsequently. The product concentrations of ethylene glycol butyl ether
      ranged from 0.5% to 9.9%. Two of the 24 children ingested > 15 mL and were
      treated by gastric emptying and 24 h hospital observation. Neither hospitalized
      child suffered symptoms consistent with hemolysis, nervous system depression,
      acidosis, or renal compromise. Dilution with oral fluids at home is considered
      appropriate treatment of pediatric ingestions of < 10 mL of a commercial liquid
      glass/window cleaners containing < 10% ethylene glycol butyl ether.

PMID- 1359161
TI  - A comparison of the sedative effects of three alpha 2-adrenoceptor agonists
      (romifidine, detomidine and xylazine) in the horse.
AB  - The sedative effects of a new alpha 2-adrenoceptor agonist, romifidine, were
      compared with those of xylazine and detomidine. Five horses were treated with two
      doses of romifidine (40 micrograms/kg body weight and 80 micrograms/kg body
      weight), two doses of detomidine (10 micrograms/kg body weight and 20
      micrograms/kg body weight) and one dose of xylazine (1 mg/kg body weight) given
      by intravenous injection using a Latin-square design. The dose of 80
      micrograms/kg romifidine appeared equipotent to 1 mg/kg xylazine and 20
      micrograms/kg detomidine, although at these doses both xylazine and detomidine
      had a shorter action. Detomidine 20 micrograms/kg and xylazine both produced
      greater lowering of the head and a greater degree of ataxia than romifidine at
      either dose. Romifidine produced sedation similar to that of the other drug
      regimes. The effect upon imposed stimuli was similar.

PMID- 1359162
TI  - International Workshop on Reflux and Pyelonephritis. New Orleans, Louisiana,
      October 23-25, 1991.

PMID- 1359163
TI  - Immunodeficiency and the risk of death in HIV infection.
AB  - OBJECTIVE: To describe the rate of development of immunodeficiency in human
      immunodeficiency virus (HIV) infection and to relate this to the risk of death.
      DESIGN: Inception cohort followed up for up to 12 years from HIV seroconversion
      until January 1, 1992. SETTING: A regional hemophilia center based in a major
      teaching hospital. PATIENTS: All 111 patients with hemophilia who seroconverted
      to HIV-1 between 1979 and 1985 were registered at the center. Patients have been
      closely followed up clinically and immunologically. OUTCOME MEASURES: Development
      of immunodeficiency, defined by a CD4 lymphocyte count falling beneath 0.20 and
      0.05 x 10(9)/L, and death. RESULTS: Kaplan-Meier estimates suggest that almost
      half (46%; 95% confidence interval [CI], 26% to 66%) of patients alive 12 years
      after seroconversion will have a CD4 lymphocyte count that has remained above
      0.05 x 10(9)/L. Thirty-five percent (95% CI, 22% to 48%) remain above 0.20 x
      10(9)/L. Thirty-seven patients died of HIV-related causes, and there was a 52%
      probability (95% CI, 35% to 69%) of HIV-related mortality by 12 years from
      seroconversion. Mortality risk was closely associated with severe
      immunodeficiency. There was only a 15% chance (95% CI, 6% to 25%) of HIV-related
      death occurring before a CD4 count of below 0.05 x 10(9)/L had been reached.
      There was an average of one HIV-related death per 96.7 patient-years of
      observation before the CD4 count had fallen below 0.05 x 10(9)/L, as compared
      with one death per 2.5 patient-years of observation after the CD4 count had
      fallen below this level (P < .0001). CONCLUSIONS: In patients with HIV infection
      who are closely followed up, the risk of death is low before the CD4 lymphocyte
      count has fallen to 0.05 x 10(9)/L, a count many patients remain above up to 12
      years after seroconversion.

PMID- 1359164
TI  - Immunologic aspects of cardiovascular disease.
AB  - The spectrum of vasculitis is diverse, and numerous entities do not fit the
      aforementioned broad categories. Examples of these include Buerger's disease;
      vaso-occlusive vasculitis of the lower extremities associated with cigarette
      smoking; Behcet's disease, which is prevalent in the Orient and Middle East and
      is characterized by recurrent aphthous stomatitis, genital ulcerations, uveitis,
      meningoencephalitis, and phlebitis; and isolated central nervous system
      vasculitis, a rare disease with a poor prognosis that primarily affects
      intracranial arteries without a systemic acute-phase response. Improvement in the
      classification and definitive therapy of vasculitis awaits identification of
      etiologic agents and definition of host factors and the immune response
      responsible for the pathology.

PMID- 1359165
TI  - Genetic analysis of dilated cardiomyopathy--HLA and immunoglobulin genes may
      confer susceptibility.
AB  - To identify genetic factors in the immune system which control the susceptibility
      to dilated cardiomyopathy (DCM), HLA class II DNA typing was performed in 61
      Japanese patients, using PCR/SSO probe analyses. The frequencies of HLA-DQB1*0503
      (15% vs 5%; RR = 3.06, chi 2 = 7.19) and DQB1*0604 (21% vs 10%; RR = 2.41, chi 2
      = 6.20) were significantly increased and that of HLA-DQB1*0502 (RR = 1.74) was
      slightly increased in the DCM patients. The frequency of DQB1*0303 (16% vs 31%;
      RR = 0.44, chi 2 = 5.16) was significantly decreased in the patients. The
      increased HLA-DQB1 alleles have a histidine residue in common at the 30th codon
      for the HLA-DQ beta chain. Among the genetic markers studied by Southern blot
      analyses, IGLV (immunoglobulin lambda light chain, pV3.3) showed a strong
      association with DCM, i.e. A2/A2 genotype was found in 37.7% of patients whereas
      it was observed in only 18.9% of the control subjects (RR = 2.6, chi 2 = 7.77).
      The frequency of this genotype was higher in patients under age 45 years at the
      time of diagnosis (45.5%, RR = 3.6, chi 2 = 10.02). These results suggest that
      HLA and immunoglobulin genes are closely linked to susceptibility to DCM.

PMID- 1359166
TI  - [Evaluation of the timing principle with small priming doses of vecuronium].
AB  - The intubating conditions using the timing principle combined with small priming
      doses of vecuronium were evaluated in forty patients who underwent elective
      surgery. They were randomly assigned to one of two groups: 1) timing, 2) timing
      with priming. In timing group, vecuronium 0.15 mg.kg-1 was administered, and at
      the onset of clinical muscle weakness, thiopental 4-5 mg.kg-1 was given promptly.
      Sixty seconds after thiopental, patients were intubated. In the timing with
      priming group, vecuronium 0.005 mg.kg-1 was administered as priming doses. Four
      minutes later vecuronium 0.15 mg.kg-1 was given. The administration of thiopental
      and the intubation were done in the same way as in timing group. The time to
      onset of clinical weakness after the administration of vecuronium 0.15 mg.kg-1
      was significantly shorter in the timing with priming group than that in the
      timing group (46.1 +/- 4.8 vs. 57.6 +/- 7.8, P < 0.01). There were no significant
      differences in intubating score, T1, TR, onset time, and duration between the two
      groups. We conclude that the timing principle combined with small priming doses
      of vecuronium might be safe and useful for rapid tracheal intubation.

PMID- 1359167
TI  - [Effects of epithelium removal and cooling on tracheal contraction in guinea
      pigs].
AB  - We investigated the effects of epithelium removal and cooling (32 degrees C, 27
      degrees C, 22 degrees C) on isolated tracheal smooth muscle contraction induced
      by bethanechol (BCh), acetylcholine (ACh), histamine (Hist), and KCl in guinea
      pigs. The pD2 values (-logED50) increased in the epithelium damaged group
      compared with the intact group when ACh was administered at 37 degrees C, 32
      degrees C, 27 degrees C and 22 degrees C, with histamine at all four temperature
      conditions, and with KCl at 37 degrees C, 32 degrees C and 27 degrees C. In both
      groups, the pD2 values for BCh, ACh, and KCl tended to decrease as temperature
      was lowered, and significant decrease in pD2 was observed at 27 degrees C. In
      contrast, the pD2 value for histamine tended to increase as temperature was
      lowered in every group. Concerning these agents, we conclude that epithelium
      removal and cooling exert neither significant nor consistent effect on tracheal
      epithelial function.

PMID- 1359168
TI  - [Rapid induction with vecuronium/fentanyl combinations for coronary artery
      surgery: influence on cardiovascular responses and plasma fentanyl
      concentrations].
AB  - Cardiovascular effects of fentanyl (60 micrograms.kg-1.min-1)/vecuronium
      combination for rapid induction were studied in fifty five patients for coronary
      artery bypass grafts. Cardiovascular and cerebral profiles of patients who had
      rapid fentanyl administration (39 patients) or slow fentanyl administration (15
      patients) were compared with base line values and between each group. Plasma
      samples were assayed for epinephrine, norepinephrine, growth hormone, anti
      diuretic hormone and fentanyl. There were no differences in all hemodynamic
      parameters between each group. However, in the rapid administration group,
      statistically significant changes were detected in the heart rate, cardiac index,
      stroke volume index and left ventricular stroke work index. The changes in the
      heart rate were small and returned to the baseline value after sternotomy. A
      decrease in cardiac index after induction depends on a decrease in stroke volume
      index rather than in the heart rate. In rapid administration group, the EEG
      showed low frequency activity within a minute. The hormonal stress responses were
      significantly attenuated in both groups. High plasma concentrations of fentanyl
      could be achieved at the intubation. The data demonstrate that rapid induction by
      fentanyl is safe and convenient.

PMID- 1359169
TI  - [Varicella-zoster virus infection after peripheral blood stem cell autografts in
      children with leukemia or non-Hodgkin's lymphoma].
AB  - Thirty-two patients with leukemia or non-Hodgkin's lymphoma (NHL) who underwent
      high-dose chemotherapy without total body irradiation (TBI) and peripheral blood
      stem cell autografts (PBSCT) were evaluated for the occurrence of clinically
      manifested varicella-zoster virus infection (VZV). In a minimum follow-up of 3
      mo, there were 14 cases with VZV; 12 patients were treated with intravenous
      acyclovir and 2 patients received additional intravenous VZV hyperimmune
      immunoglobulin preparations. History of previous varicella-zoster at some time
      before PBSCT was the only significant risk factor for the development of VZV.
      Furthermore, a significant association between VZV and higher disease-free
      survival rate after PBSCT was proved. Development of minor and reversible VZV is
      rather common event after high-dose chemotherapy without TBI and PBSCT. VZV
      appears to be one of the factors which reflects basic physiologic mechanism
      preventing relapse of leukemias or NHL after PBSCT.

PMID- 1359170
TI  - [Inversion of chromosome 16 observed in acute myeloblastic leukemia (M2) with
      biphenotypic surface markers lacking monocytosis and eosinophilia].
AB  - Inversion of chromosome 16 was found in a 73-year-old female with acute
      myeloblastic leukemia (FAB:M2). Complete remission was achieved by combined
      chemotherapy (DNR, Ara-C, 6-MP, Prednisolone), but she relapsed 6 months later
      without CNS involvement and died of respiratory failure presumably due to
      cerebrovascular accident during remission reinduction chemotherapy. Biphenotypic
      surface markers (CD2+ and CD13+) were observed on relapse. Eosinophilia was not
      observed throughout. Our patient and the other reported case suggest that
      biphenotypism and the lack of eosinophilia and monocytosis in inv (16) leukemia
      may be correlated with a poor prognosis.

PMID- 1359171
TI  - [Function and molecular structure of IL-12].
AB  - Natural killer cell stimulatory factor (NKSF), also called cytotoxic lymphocyte
      maturation factor (CLMF) or interleukin-12, is a novel cytokine of a 70 kDa
      heterodimer, composed of two covalently linked glycosylated chains of 40 and 35
      kDa. NKSF was originally identified in the supernatant fluid of human EB virus
      transformed B lymphoblastoid cell lines. NKSF has been shown to: (a) induce
      interferon-gamma production from both T and NK cells and synergize in this effect
      with interleukin-2 (IL-2), mitogens, phorbol diesters, anti-CD3 antibodies, and
      allogeneic antigens; (b) exert a comitogenic effect on fresh resting T cells
      together with lectins or phorbol diesters; (c) mediate a direct mitogenic effect
      on activated T or NK cell blasts; (d) enhance the cytotoxic activity of resting
      peripheral blood NK cells; and (e) synergize with IL-2 in the generation of
      lymphokine-activated killer cells.

PMID- 1359173
TI  - Marked increase of CD57+CD16- cells in long-term survivors of graft-versus-host
      disease after allogeneic bone marrow transplantation.
AB  - We have evaluated long-term serial changes in the immunological state from soon
      after allogeneic bone marrow transplantation (BMT) In 44, mainly leukemia
      patients with respect to changes in lymphocyte surface markers. Absolute numbers
      of cluster designation (CD)2+, CD20+ and human lymphocyte antigen-DR+ (HLA-DR+)
      cells recovered to within their normal ranges three months, one year and two
      years, respectively, after BMT. The reversal of the CD4+: CD8+ ratio persisted
      for five years or more but returned to normal after six years. CD57+CD16- cells
      were markedly increased from three mo up to a maximum of five years after
      transplantation; they were increased between three and six months after
      transplantation irrespective of graft-versus-host disease (GVHD), but changes
      after one year or more differed among patients without GVHD, with acute GVHD,
      with acute and chronic GVHD or with chronic GVHD. Absolute numbers of CD57+CD16-
      cells tended gradually to return to normal after one year or more in the group
      without GVHD but only after six years in patients in the other three GVHD groups.

PMID- 1359172
TI  - Production of immunoreactive corticotropin-releasing hormone in various
      neuroendocrine tumors.
AB  - The concentrations of immunoreactive (IR) corticotropin-releasing hormone (CRH)
      in 218 neuroendocrine tumors were determined by CRH radioimmunoassay. The tumors
      examined were 86 pancreatic endocrine tumors (PET), 22 neuroblastic tumors (NBT),
      26 carcinoid tumors (CA), 24 pheochromocytomas (PHEO), 40 small cell lung
      carcinomas (SCLC) and 20 medullary thyroid carcinomas (MTC). IR-CRH was
      detectable in 21 neuroendocrine tumors (10 PET, four NBT, three CA, two PHEO and
      two SCLC) at levels of 10-2,700 ng/g wet weight (9.6%). The 21 patients with
      these CRH-producing tumors showed no clinical symptoms suggestive of Cushing's
      syndrome. The levels of plasma IR-CRH extracted by immunoaffinity chromatography
      were < 7.5 pg/ml in five normal subjects and a patient with a neuroblastic tumor
      containing 55 ng/g wet weight IR-CRH, but in a patient with a thymic carcinoid
      tumor containing 1,000 ng/g wet weight IR-CRH, the plasma level was elevated to
      180 pg/ml. This patient did not have Cushing's syndrome nor an elevated plasma
      adrenocorticotropic hormone (ACTH) level. The concentrations of nine peptides
      (growth hormone-releasing hormone, somatostatin, ACTH, calcitonin, gastrin
      releasing peptide, glucagon, vasoactive intestinal peptide, neuropeptide tyrosine
      and pancreatic polypeptide) were determined in extracts of the 21 IR-CRH
      producing tumors. Some of these peptides were frequently found to be produced
      concomitantly with CRH. The results indicate IR-CRH to be produced by various
      neuroendocrine tumors, but Cushing's syndrome, due to the CRH, to be very rare.
      The results also show that CRH-producing tumors produce multiple hormones.

PMID- 1359175
TI  - [The 34th Congress of the Japanese Geriatric Society. Kanazawa, November 19-21,
      1992. Abstracts].

PMID- 1359174
TI  - Prognostic factors for recurrent breast cancer: univariate and multivariate
      analyses including histologic grade and amplification of the c-erbB-2 proto
      oncogene.
AB  - Post-recurrence survival was examined in 62 breast cancer patients who had
      undergone curative radical mastectomies between 1974 and 1976 and suffered
      recurrences within 127 months of surgery. The prognostic value of 11 clinical,
      histological and genetic factors, including histologic grade of malignancy and
      amplification of oncogenes was analyzed using univariate and multivariate
      analyses. Not only the site of first recurrence, clinical stage and size of
      primary tumor at initial surgery, and disease-free period, but also histologic
      grade and amplification of the c-erbB-2 proto-oncogene were significant
      prognostic indicators of recurrent breast cancer. Multivariate analysis using
      Cox's regression model, histologic grade and amplification of c-erbB-2 in the
      primary tumor, as well as clinical stage at surgery and site of first recurrence,
      were shown to be major independent prognostic factors of recurrent breast cancer.
      Because post-recurrence prognosis was strongly influenced by the clinical,
      histological and genetic status of the primary breast cancer, appropriate
      evaluation of the primary tumor for the grade of aggressiveness of the cancer
      cells, as well as the extent of cancer spread, seem to be important.

PMID- 1359176
TI  - Sympathetic vasoconstrictor tone induced by pentobarbital anesthesia in
      hindquarters of rats.
AB  - Hindquarter (terminal aortic) blood flow (HQF) and arterial pressure (AP) were
      observed in rats with an electromagnetic flow probe implanted around the terminal
      aorta and an arterial indwelling cannula. Hindquarter peripheral resistance (HQR)
      was calculated by dividing mean AP by HQF. Under pentobarbital anesthesia, HQR
      was decreased significantly (p less than 0.001) by ganglionic blockade with
      hexamethonium bromide (C6). Since C6 does not change HQR significantly without
      anesthesia, we interpret that pentobarbital anesthesia generated a sympathetic
      vasoconstrictor tone in hindquarter resistance vessels. This was further
      substantiated by the observation that the increase in HQR on infusion of
      vasopressin was obscure under pentobarbital anesthesia: Presumably, the increase
      was offset by reflex inhibition of the hindquarter tone induced by anesthesia.
      The generation of hindquarter vasoconstrictor tone by pentobarbital was for the
      most part ascribable to the baroreceptor reflex to compensate for the depressor
      effect of this anesthetic, because it was greatly diminished after severance of
      the buffer nerves.

PMID- 1359177
TI  - Conditioning stimulation of the central amygdaloid nucleus inhibits the jaw
      opening reflex in the cat.
AB  - To elucidate a function of the central amygdaloid nucleus (ACE) in the trigeminal
      system, the ACE conditioning effect on the jaw-opening reflex (JOR) regarded as a
      nociceptive reflex was investigated in the cat anesthetized with pentobarbital
      sodium. The JOR to molar tooth pulp stimulation with an intensity 1.2-1.5 times
      the threshold was recorded in the ipsilateral digastric muscle. As conditioning
      stimulation, a train of 33 rectangular pulses (0.5 ms in duration) at 330 Hz with
      an intensity of 300 microA was applied to the ipsilateral ACE. The conditioning
      stimulation inhibited a JOR that had a latency of 7.90 +/- 0.88 ms (n = 36). The
      inhibition was maximum (83.1 +/- 11.2%) at a conditioning-test (C-T) interval of
      110 ms and continued for C-T intervals of up to 1,000 ms. Likewise,
      microinjection of 0.5 M monosodium glutamate (10 microliters) into the ACE
      inhibited the JOR for approximately 10 min. Additionally, the ACE conditioning
      stimulation inhibited the JOR induced by the stimulation of the sensory
      trigeminal nuclear complex in a similar manner, but not the jaw-opening response
      induced by the stimulation of the trigeminal motor nucleus (Mo V). Also, the
      conditioning stimulation influenced neither the evoked potentials induced by the
      tooth pulp stimulation at the main sensory and rostral nuclei nor the jaw-closing
      reflex induced by the stimulation of the mesencephalic trigeminal nucleus (Mes
      V). These results suggest that the excitation of the cell bodies in the ACE
      exerts an inhibitory modulation on the JOR with no effect on the non-nociceptive
      reflex such as the jaw-closing reflex at the level of Mo V.

PMID- 1359178
TI  - Effects of a new histamine H2-receptor antagonist, Z-300, on gastric secretion
      and gastro-duodenal lesions in rats: comparison with roxatidine.
AB  - We examined the effects of a new compound, N-[3-[3-(piperidinomethyl)phenoxy]
      propyl]-2-(2-hydroxyethyl-1- thio)acetamido.2-(4-hydroxy benzoyl)benzoate (Z
      300), on the histamine H2-receptor, gastric secretion in rats and dogs, and acute
      gastro-duodenal lesions or chronic gastric ulcers in rats. Roxatidine acetate
      hydrochloride (roxatidine), a known histamine H2-receptor antagonist, was used as
      a reference compound. The pA2 values for Z-300 and roxatidine for the isolated
      guinea pig atrium were 6.8 and 7.0, respectively. These agents at less than 10(
      5) M did not affect the contraction of guinea pig ileum in response to carbachol.
      Z-300, administered either orally or parenterally, significantly inhibited the
      basal and histamine-stimulated gastric acid secretion in rats. Gastric acid
      secretion stimulated by histamine, pentagastrin or carbachol in Heidenhain pouch
      dogs was also significantly inhibited by the compound. The effect persisted for
      greater than 7 hr in the case of histamine-stimulation. Oral Z-300 significantly
      protected the gastric mucosa from water-immersion stress-, indomethacin-, aspirin
      and HCl.ethanol-induced lesions and protected the duodenal mucosa against
      mepirizole- and cysteamine-induced ulcers. These effects on gastric secretion and
      lesion formation were, as a whole, stronger than those observed with roxatidine.
      Z-300, but not roxatidine, significantly accelerated the spontaneous healing of
      acetic acid ulcers induced in rats and prevented the delay in ulcer healing
      caused by indomethacin. The mechanism of action of Z-300 on acute lesions and
      chronic ulcers appears to be mostly related to its potent antisecretory and
      mucosal-protective activities.

PMID- 1359179
TI  - In vitro pharmacological profile of the novel alpha 1-adrenoceptor antagonist HSR
      175.
AB  - The pharmacological profile of HSR-175, a new alpha 1-adrenoceptor antagonist,
      was studied in vitro and compared with those of other alpha 1-antagonists. HSR
      175, prazosin, bunazosin and yohimbine competitively antagonized the contractile
      responses induced by noradrenaline in the dog mesenteric arteries and the rabbit
      thoracic aorta. The pA2 values for HSR-175 in the dog mesenteric arteries and the
      rabbit aorta were 10.38 and 9.63, respectively, which were significantly higher
      than those for prazosin (8.39 and 8.80), bunazosin (8.44 and 8.75) and yohimbine
      (7.34 and 6.10). HSR-175 also inhibited the sympathetic adrenergic contraction
      induced by electrical transmural stimulation in the dog mesenteric arteries, and
      the inhibitory effect of HSR-175 was more potent than those of prazosin and
      bunazosin. Although HSR-175 also possessed competitive antagonist properties at
      pre- and postsynaptic alpha 2-adrenoceptors in the rat vas deferens and the dog
      saphenous veins, those affinities (pA2 = 6.41 and 7.05) were much lower than
      those at postsynaptic alpha 1-adrenoceptors. Furthermore, HSR-175 at
      concentration of 10(-6) M showed no inhibition on the contractile responses to 5
      HT, histamine, KCl and angiotensin II in the rabbit thoracic aorta. These results
      indicate that HSR-175 is a very potent and selective alpha 1-adrenoceptor
      antagonist.

PMID- 1359180
TI  - Characteristics of the association of brotizolam, a thieno-triazolo diazepine
      derivative, with the benzodiazepine receptor: a selective and high affinity
      ligand of the central type I benzodiazepine receptor.
AB  - Characteristics of the association of brotizolam, a thieno-triazolo diazepine
      derivative, to central benzodiazepine receptors were examined. Brotizolam
      significantly displaced the [3H]flunitrazepam and [3H]beta-carboline carboxylate
      ethylester bindings to crude synaptic membrane from the rat brain. This agent had
      the highest affinity for benzodiazepine receptors in the cerebellum, and it was
      found to be 2.1 times that in the spinal cord. Furthermore, a low concentration
      of brotizolam potentiated the GABA-stimulated 36Cl- influx into membrane
      vesicles. In contrast, the bindings of [3H]8-hydroxy-2-(di-n-propylamino)tetralin
      to 5-hydroxytryptamine1A receptors and [3H]ketanserin to 5-hydroxytryptamine2
      receptors were not affected by brotizolam. The present results suggest that
      brotizolam may be a selective and high affinity ligand for the type I central
      benzodiazepine receptor. The anxiolytic and hypnotic actions of brotizolam seem
      to be not due to the association with 5-hydroxytryptamine receptor, but due to
      the activation of the GABAA receptor complex. Furthermore, the present results
      suggest that the lower affinity of brotizolam to benzodiazepine receptors in the
      spinal cord than those in the cerebellum may be related to the low muscle
      relaxation action of this drug.

PMID- 1359181
TI  - Tryptophan inhibits the [3H]glutamate uptake into Xenopus oocytes injected with
      rat brain mRNA.
AB  - We characterized the glutamate (Glu) uptake in Xenopus oocytes injected with rat
      brain mRNA. The Glu uptake into oocytes was higher in mRNA-injected oocytes than
      in vehicle-injected ones. Na+ omission or addition of tryptophan inhibited the
      uptake in mRNA-injected oocytes, although it did not affect that in vehicle
      injected oocytes. These results suggest that Glu transporters with a tryptophan
      sensitivity different from that of Glu transporters in native oocytes are
      expressed after injection of rat brain mRNA.

PMID- 1359182
TI  - Kindling seizure induction and excitatory amino acid.

PMID- 1359183
TI  - The function of poly(A) tract in vitro protein synthesis of seizure-prone E1
      mouse brain.

PMID- 1359184
TI  - Changes of immunoreactive somatostatin, neuropeptide Y, and corticotropin
      releasing factor (CRF) in the brain of spontaneously epileptic rats (SER).

PMID- 1359185
TI  - [Bronchial hyperresponsiveness to acetylcholine during acute pulmonary congestion
      in guinea pigs].
AB  - To understand the precise mechanism of bronchial hyperresponsiveness in patients
      with congestive heart failure, we studied the effect of mild pulmonary congestion
      on bronchial responsiveness to inhaled acetylcholine (ACh) in guinea pigs. We
      induced mild pulmonary congestion by inflation of a balloon placed in the left
      atrium, and maintained the left atrial pressure (Pla) at 10 mmHg for 30 minutes
      with continuous monitoring of lung resistance (RL) and dynamic compliance (Cdyn).
      Furthermore, we determined the provocative concentration of ACh producing 100%
      increase in RL (PC100-ACh), before and during balloon inflation. In animals with
      propranolol pretreatment, but not in animals without propranolol pretreatment,
      mild pulmonary congestion caused slight increase in RL (N.S.) and significant
      decrease in Cdyn (p less than 0.01) and PC 100-ACh (p less than 0.01). Cutting of
      bilateral vagal nerves partially inhibited the decrease of PC100-ACh, but
      pretreatment with either phenoxybenzamine, indomethacin, AA-861 or OKY-046 had
      not effect. These results suggest that blockade of beta-adrenergic receptors and
      the vagal reflex, but not of alpha-adrenergic receptors or arachidonates,
      contributes to bronchial hyperresponsiveness during acute pulmonary congestion.

PMID- 1359186
TI  - [Encephalitis, meningitis serosa and parotitis after MMR preventive vaccination?
      The Pediatric Vaccination Counseling Unit].

PMID- 1359188
TI  - [Legal occupational rights: termination of a long-term physician's assistant].

PMID- 1359187
TI  - [Incubation vaccination ("post-exposure vaccination") with MMR vaccine during a
      mumps epidemic? The Pediatric Vaccine Counseling Unit].

PMID- 1359189
TI  - [Eurocity: Vienna--Frankfurt].

PMID- 1359190
TI  - [First European meeting of nursing schools. Space for common projects!].

PMID- 1359191
TI  - [There is always a borderline somewhere].

PMID- 1359192
TI  - Molecular basis of 3-ketothiolase deficiency: detection of gene mutations and
      expression of mutant cDNAs of mitochondrial acetoacetyl-CoA thiolase.

PMID- 1359193
TI  - Characterization of primary human fetal dissociated central nervous system
      cultures with an emphasis on microglia.
AB  - BACKGROUND: We undertook a systematic examination of human fetal central nervous
      system dissociated cell cultures, particularly with respect to microglia and
      their dynamic interactions with other central nervous system cell components.
      EXPERIMENTAL DESIGN: The growth and differentiation of astrocytes, microglia, and
      small immature neuronal cells in mixed and single cell type-enriched cultures
      were followed by phase contrast microscopy, immunocytochemistry, flow cytometry,
      electron microscopy and immunoelectron microscopy, in regard to their phenotype
      change, proliferation and class II major histocompatibility complex antigen
      expression. RESULTS: Both astrocytes and microglia expressed marked phenotype
      heterogeneity, but they were consistently positive for glial fibrillary acidic
      protein and CD68, respectively. Highly enriched astrocyte and microglial cultures
      suitable for biochemical or molecular biologic studies were obtained. Using
      double immunocytochemical labeling techniques with the proliferating cell nuclear
      antigen and cell-type specific markers, astrocytes grown in serum-containing
      media showed a high labeling index, whereas microglia seldom exhibited a similar
      degree of proliferative activity. Microglia, however, proliferated in response to
      certain growth factors, such as granulocyte macrophage colony-stimulating factor.
      Both microglia and astrocytes expressed high basal levels of class II MHC
      antigens, which further increased with addition of interferon-gamma. The
      microglia in dissociated cultures existed in two forms, ameboid and ramified.
      Microglial ramification was induced when ameboid microglia were co-cultured with
      a monolayer of astrocytes, suggesting a role for astrocytes in microglial
      differentiation. In addition, lipopolysaccharide in nanogram amounts consistently
      enhanced microglial survival and morphologic differentiation. The small bipolar
      cells, the most frequent cell type in mixed culture, were glial fibrillary acidic
      protein (-) and CD68 (-), and their size and shape remained unchanged under our
      culture conditions. A subpopulation of small bipolar cells was stained positive
      with an antibody to surface ganglioside, A2B5. Electron microscopic examination
      showed that their processes contained parallel microtubules bearing side arms
      consistent with immature neurons. CONCLUSIONS: Highly purified astrocyte and
      microglial cultures are obtained using the currently described technique. The
      current culture system is a valuable tool in studying human central nervous
      system biology and disease.

PMID- 1359194
TI  - Mechanisms of somatostatin action in RINm5F cells in culture: preliminary
      evidence for possible altered G protein function.
AB  - Octreotide (SMS), a somatostatin analogue, is an established antigrowth peptide,
      but it does not effectively inhibit the growth of insulinoma cells. In order to
      study the mechanisms that underlie this apparent lack of an antiproliferative
      effect on insulinoma tumor cells we established the rat insulinoma cell line,
      RINm5F, in culture. Cells in culture were tested by incubation in media with and
      without SMS. To study tritiated [3H]-thymidine incorporation into extracted DNA
      (TTID), 2 muCi/well of 3H was added for 24 hr, and cells were harvested and
      assayed for TTID (cpm/microgram DNA). Insulin (IRI) and intracellular cAMP
      (cAMPi) were measured by RIA. To study the effects of SMS on insulin secretion,
      conditioned media were sampled after 24 hr. To study the effects of cAMPi,
      conditioned medium was used to extract cAMPi following incubation with SMS for 15
      min. Increasing concentrations of SMS had no significant effect on TTID in the
      presence of 1% FBS. Trypan blue exclusion tests showed > 90% viable cells
      throughout all stages of these experiments. There were no significant differences
      in cell numbers and protein content in the presence of SMS. There was a
      significant decrease in the secretion of insulin and intracellular cAMP levels in
      response to 50 nM SMS. However, SMS significantly inhibited TTID in RINm5F cells
      following a 4-hr pretreatment with pertussis toxin (PT) (23553 +/- 1747 vs 20635
      [cpm/microgram DNA] +/- 1983 [SEM], P < 0.01). We conclude that the inhibition of
      insulin secretion by SMS is associated with an attenuation of cAMP
      formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359195
TI  - Proliferative activity in gastric cancer determined with cell cycle-related
      monoclonal antibodies Ki-67 and p105: analysis by flow cytometry.
AB  - The proliferative activity of gastric cancer cells was determined by DNA flow
      cytometric (FCM) analysis and labeling rates of Ki-67 and monoclonal antibodies
      and proliferation-associated nuclear antigen (p105) autoantibodies in 28 patients
      with fresh human gastric cancer cells. By setting the cutoff line at the level as
      used in a negative control study without primary antibody in the same sample, the
      Ki-67 and p105 labeling rates were calculated by the dual fluorescence analysis.
      A total of 43 experiments was performed on FCM analysis for each antigen: 28 with
      Ki-67 and 15 with p105. The mean Ki-67 labeling rate of gastric cancer cells was
      45.1% (13.9-76.3%). The Ki-67 labeling rates were significantly higher for larger
      size tumor, peritoneal metastasis, and advanced clinical stage. A significant
      correlation was found between Ki-67 labeling rate and p105 labeling rate (P <
      0.05). Bivariate FCM may be an easy method for obtaining useful information of
      cell kinetics.

PMID- 1359196
TI  - Structural alterations of the p53 gene in human leukemias.
AB  - We have investigated alterations of the p53 gene in human leukemias by polymerase
      chain reaction-mediated restriction fragment length polymorphism analysis. This
      method detects the codon 72 polymorphism of the p53 gene, allowing identification
      of loss of heterozygosity (LOH) of the p53 gene. In this study, at least two
      specimens were obtained from each patient to compare the allele status at
      different points of clinical course. Of 21 cases examined 7 were heterozygous at
      this polymorphic site and were evaluable for LOH study. Only one patient of
      Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) lost the
      heterozygosity in the specimen of her last relapse. Leukemic cells from her
      repeated relapses including the last one revealed to have the clonally rearranged
      immunoglobulin H chain gene of the same size, indicating that alteration of the
      p53 gene in this patient might account for the lethal relapse as a clonal
      evolution event. Northern-blot analysis of the p53 gene showed that one case of
      CD7(+) ALL had altered p53 mRNA. Overall, it is demonstrated that alterations of
      the p53 gene might be involved in the pathogenesis or progression of at least
      some human leukemias, although the alterations in leukemias seemed to be not as
      frequent as in solid tumors.

PMID- 1359197
TI  - In vitro electroreceptor organs for pharmacological studies.
AB  - Electroreception is a well-established sensory faculty in aquatic vertebrates.
      The general physiology of the receptor organs is comprehensively documented. The
      transduction mechanism of the receptor cells and the synaptic transmission
      mechanism are less well understood. Research has been hampered by the
      inaccessibility of the synaptic site. This paper describes how to prepare an in
      vitro preparation of ampullary electroreceptor organs which allows exposure of
      both the mucosal and the serosal sides of the receptor cells to superfusion of
      test solutions. The preparation is quite robust and has been shown to function
      reliably for more than 8 h. Furthermore, the use of in vitro electroreceptors
      organs as a model for pharmacological studies is evaluated.

PMID- 1359199
TI  - Antiprogestin Drugs: Ethical, Legal and Medical Issues. Proceedings of a
      conference. December 1991.

PMID- 1359198
TI  - In situ hybridization of whole-mounts of Aplysia ganglia using non-radioactive
      probes.
AB  - A protocol for carrying out in situ hybridization with non-radioactive,
      digoxigenin-labelled probes has been developed for whole-mounts of Aplysia
      ganglia. Whole-mount preparations preserve the anatomical relationships of
      neurons within intact ganglia and facilitate the precise identification of a
      particular neuron in live preparations so that functional studies can be
      correlated with biochemical attributes of an identified neuron. The protocol was
      developed with the use of probes to messenger RNAs that are abundant in Aplysia
      neurons. In situ hybridization with a cDNA probe to a neuronal form of beta-actin
      stained all neurons, including their processes, whereas use of a cDNA probe for
      the neuropeptide FMRFamide resulted in staining of a select group of Aplysia
      neurons.

PMID- 1359200
TI  - Leukemia 1992. Proceedings of the 2nd International Course: Recent Progress in
      Biology and Clinical Research in Adult Leukemia. Genoa, Italy, 4-7 July 1992.

PMID- 1359201
TI  - New developments in peripheral blood stem cell transplants.

PMID- 1359202
TI  - Intensive conventional chemotherapy can lead to a precocious overshoot of
      cytogenetically normal blood stem cells (BSC) in chronic myeloid leukemia and
      acute lymphoblastic leukemia.
AB  - Forty patients with Ph-positive blastic phase (BP) (28 patients) or chronic phase
      (CP)-CML (3 patients) and relapsed adult acute lymphoblastic leukemia (ALL) (9
      patients) with cytogenetical translocations [t(8;14):2 patients; t(4;8):2
      patients; t(4;11):3 patients; t(9;22):2 patients], received an intensive
      conventional chemotherapy. During early recovery from marrow aplasia, when WBC
      reached 0.3-1.5 x 10--9/L, peripheral blood stem cells (BSC) were collected by 4
      8 leukapheresis consecutively. BSC collected from the 2/3 patients with CP-CML
      resulted Ph-negative and PCR negative. In 8 out of 26 BP-CML patients, BSC
      resulted Ph-negative and in two cases PCR negative. Of the nine ALL patients, 6
      patients lost the cytogenetic translocations, one patient died during aplasia,
      two patients did not have cytogenetic modifications and died in few weeks of
      leukemia and one patient out of six responding patients relapsed before
      transplant. After complete recovery, 15 patients (BP-CML:8 patients; CP-CML:2
      patients; ALL:5 patients) were subsequently given high-dose therapy (VP-16 +/-
      Cy+TBI in single dose) followed by reinfusion of "normal" BSC. Both the patients
      in CP-CML and 5/5 patients with ALL maintain clinical and cytogenetic remission;
      all the patients transplanted in BP-CML relapsed 5-18 months post-transplant. It
      is concluded that intensive conventional chemotherapy employed in CML and ALL can
      lead to a precocious overshoot of cytogenetically normal BSC.

PMID- 1359203
TI  - New drugs in the treatment of chronic lymphocytic leukemia.

PMID- 1359205
TI  - Myeloablative regimens in peripheral stem cell transplantation.
AB  - There is considerable opportunity for research in identifying the relative merits
      of various preparatory regimens utilized for high dose therapy in autologous
      peripheral stem cell transplantation. These include studies of the dose level of
      a particular regimen (e.g., CBV). There is some suggestion in the literature that
      a dose response effect exists even at high doses. Studies of the relative merits
      of different drugs such as cyclophosphamide, melphalan, and hydroxyurea that have
      all been added to the CBV regimen need to be carried out. The contribution of TBI
      also remains uncertain. However, these studies require prospective, randomized
      trials that will probably have to be performed on a multi-institutional basis. It
      is also possible that future uses of hematopoietic growth factors will
      significantly modify concerns about safety with any regimen.

PMID- 1359204
TI  - Biological markers and minimal residual disease in hairy cell leukemia.
AB  - Soluble Interleukin-2 Receptor (sIl-2R) and Tumor Necrosis Factor-alpha (TNF
      alpha) have been found significantly increased in serum samples of patients with
      HCL at diagnosis and a strict correlation with leukemic burden has been reported.
      Furthermore, following therapy, serological monitoring of these cytokines may be
      considered a useful tool for controlling therapeutic efficacy and for detection
      of minimal residual disease. Eighteen HCL patients, treated with 2
      Chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg daily for 7 days, entered the
      study all of them showing increased levels of sIL-2R and TNF-alpha prior to
      therapy. After therapy, serum levels were reassessed and a remarkable decrease
      was recorded in all cases. In particular, after 1 month by the end of treatment
      sIL-2R and TNF-alpha decreased from 3,377 +/- 2,303 to 149 +/- 96 pM/ml (p =
      0.00003) and from 38 +/- 41 to 18 +/- 18 pg/ml (p = 0.015) respectively. The only
      3 patients who did not normalize sIL-2R and TNF-alpha levels showed also an
      evident persistence of the disease in the marrow. In conclusion, 2-CdA leads to a
      rapid normalization of the increased levels of sIL-2R and TNF-alpha in the
      majority of HCL patients. Furthermore, monitoring of these cytokines represents a
      useful tool for detecting minimal residual disease.

PMID- 1359206
TI  - Medical therapy for ocular allergy.
AB  - The ocular manifestations of allergy have traditionally been classified into four
      categories--namely, hay fever conjunctivitis, vernal keratoconjunctivitis, atopic
      keratoconjunctivitis, and contact lens-associated giant papillary conjunctivitis.
      Typically, hay fever conjunctivitis is characterized by mild conjunctival
      inflammation, whereas the other disorders may have severe inflammation and
      clinical manifestations. Potentially blinding corneal complications may result
      from vernal keratoconjunctivitis and atopic keratoconjunctivitis. Although hay
      fever conjunctivitis is clearly an immediate hypersensitivity reaction, the
      immunologic mechanisms that cause vernal keratoconjunctivitis, atopic
      keratoconjunctivitis, and giant papillary conjunctivitis are primarily unknown
      and speculative. Treatment of patients with ocular allergies is often challenging
      and may necessitate collaborative efforts of an ophthalmologist and an allergist.
      Herein we discuss conventional therapy and new, promising antiallergy drugs.

PMID- 1359207
TI  - [Cholesterol--how much do we disagree?].

PMID- 1359208
TI  - [Widen the narrow scientific limits of medicine, admit the great humanistic
      knowledge of human nature].

PMID- 1359209
TI  - Non-invasive detection of endothelial dysfunction in children and adults at risk
      of atherosclerosis.
AB  - Endothelial dysfunction is an early event in experimental studies of
      atherogenesis, preceding formation of plaques. We have devised a non-invasive
      method for testing endothelial function, to find out whether abnormalities are
      present in symptom-free children and young adults at high risk of
      atherosclerosis. With high-resolution ultrasound, we measured the diameter of the
      superficial femoral and brachial arteries at rest, during reactive hyperaemia
      (with increased flow causing endothelium-dependent dilatation), and after
      sublingual glyceryl trinitrate (GTN; causing endothelium-independent dilatation)
      in 100 subjects--50 controls without vascular risk factors (aged 8-57 years), 20
      cigarette smokers (aged 17-62 years), 10 children with familial
      hypercholesterolaemia (FH; aged 8-16 years), and 20 patients with established
      coronary artery disease (CAD). Adequate scans were obtained in all but 6 cases.
      Flow-mediated dilatation was observed in arteries from all control subjects.
      Dilatation was inversely related to baseline vessel diameter (r = -0.81, p <
      0.0001); in arteries of 6.0 mm or less, mean dilatation was 10 (SE 2)%. In
      smokers, FH children, and adults with CAD, flow-mediated dilatation was much
      reduced or absent (p < 0.001 for comparison with each relevant control group).
      Dilatation in response to GTN was present in all groups. Endothelial dysfunction
      is present in children and adults with risk factors for atherosclerosis, such as
      smoking and hypercholesterolaemia, before anatomical evidence of plaque formation
      in the arteries studied. This may be an important early event in atherogenesis.

PMID- 1359210
TI  - Randomised controlled trial of laparoscopic versus mini cholecystectomy. The
      McGill Gallstone Treatment Group.
AB  - Laparoscopic cholecystectomy (LC) has gained wide acceptance for treatment of
      cholelithiasis in preference to open cholecystectomy, though it has not been
      formally compared with mini cholecystectomy (MC). We have compared these two
      techniques in a randomised trial. 70 patients with ultrasound-proven
      cholelithiasis were randomly allocated LC (38) or MC (32); 37 and 25,
      respectively, underwent the assigned procedure. The mean hospital stay (including
      1 preoperative day) was significantly shorter in the LC than the MC group (median
      3 [interquartile range 2-3] vs 4 [3-5], p = 0.001) as was duration of
      convalescence (mean 11.9 [SD 9.1] vs 20.2 [16.5] days, p = 0.04). The rate of
      return to normal activities was 1.77 times greater in the LC group than in the MC
      group (95% confidence interval 1.01-3.11, p = 0.03). In regression analysis, the
      type of cholecystectomy done was the only variable significantly associated with
      the duration of convalescence. Although there was significant postoperative
      improvement in all of three quality of life scores in both groups, LC patients
      improved more quickly than did MC patients. This randomised trial shows the
      superior effectiveness of LC over MC in treating cholelithiasis.

PMID- 1359211
TI  - Effect of vitamin and trace-element supplementation on immune responses and
      infection in elderly subjects.
AB  - Ageing is associated with impaired immune responses and increased infection
      related morbidity. This study assessed the effect of physiological amounts of
      vitamins and trace elements on immunocompetence and occurrence of infection
      related illness. 96 independently living, healthy elderly individuals were
      randomly assigned to receive nutrient supplementation or placebo. Nutrient status
      and immunological variables were assessed at baseline and at 12 months, and the
      frequency of illness due to infection was ascertained. Subjects in the supplement
      group had higher numbers of certain T-cell subsets and natural killer cells,
      enhanced proliferation response to mitogen, increased interleukin-2 production,
      and higher antibody response and natural killer cell activity. These subjects
      were less likely than those in the placebo group to have illness due to
      infections (mean [SD] 23 [5] vs 48 [7] days per year, p = 0.002). Supplementation
      with a modest physiological amount of micronutrients improves immunity and
      decreases the risk of infection in old age.

PMID- 1359212
TI  - Adult coronary artery disease probably due to childhood Kawasaki disease.
AB  - We have surveyed adult survivors of childhood Kawasaki disease (KD) who had
      coronary artery disease that could be ascribed to KD. In response to
      questionnaires sent to cardiologists throughout Japan, 21 patients (17 men, 4
      women, aged 20-63 years) with coronary lesions and a definite (2) or suspected
      (19) history of KD were reported. 5 patients had presented with acute myocardial
      infarction, 6 previous myocardial infarction, 9 angina pectoris, and 1 dilated
      cardiomyopathy. 16 patients had obstructions in two or more coronary arteries. 3
      had died and 18 were alive with serious sequelae (mitral regurgitation,
      arrhythmias, congestive heart failure). Childhood KD should be included in the
      differential diagnosis of coronary artery disease in young adults.

PMID- 1359213
TI  - Electrically stimulated gracilis sphincter for treatment of bladder sphincter
      incontinence.
AB  - Correction of total urinary incontinence due to sphincter damage is done with an
      artificial sphincter prosthesis or urinary diversion. In this pilot study we used
      graciloplasty around the bladder neck followed by electrical stimulation of this
      muscle with an implanted stimulator, which could be switched off and on by a
      magnet. Stimulus variables could be changed externally. With the stimulator on,
      urethral pressures of about 50 cm H2O were obtained. Of three patients who
      underwent the procedure, two became continent and one improved but remained
      incontinent. Dynamic graciloplasty can restore urinary incontinence.

PMID- 1359214
TI  - Cochrane's legacy.

PMID- 1359215
TI  - Sporting hearts.

PMID- 1359216
TI  - Dietary fibre: importance of function as well as amount.

PMID- 1359217
TI  - Brain biopsy for intracranial mass lesions in AIDS.

PMID- 1359218
TI  - Ginkgo biloba.

PMID- 1359219
TI  - Usefulness of clinical case-definitions in guiding therapy for African children
      with malaria or pneumonia.
AB  - The World Health Organisation has developed disease-specific clinical case
      definitions to guide management of children with fever or cough, the cardinal
      signs of malaria and pneumonia. To assess the usefulness of the case-definitions
      and to investigate their interaction, we studied children with fever or cough
      brought to a hospital in Lilongwe, Malawi. For all children, a thick blood smear
      was examined for Plasmodium falciparum parasites. Chest radiography was done only
      for children with parasitaemia and those who satisfied the clinical case
      definition for pneumonia; others were assumed to have normal chest radiographs.
      Of 1599 enrolled children, 566 (35%) had parasitaemia and 116 had radiographic
      evidence of pneumonia; 43 had both pneumonia and parasitaemia. Of the 471
      children who met the clinical definition for pneumonia, 449 (95%) also met the
      malaria clinical definition. Among children with radiographic evidence of
      pneumonia, the clinical definition for malaria was not predictive of parasitaemia
      (sensitivity 93%, specificity 5%). Whether malaria parasitaemia was present or
      absent, the pneumonia clinical definition distinguished children with and without
      radiographic evidence of pneumonia (sensitivity and specificity > 60%). Children
      who satisfied the pneumonia clinical definition were more likely to have
      radiographic evidence of pneumonia (odds ratio 10.4, 95% confidence interval 5.2
      20.7), parasitaemia (1.6, 1.2-2.2), or both at the same time (4.2, 2.1-8.4) than
      were children who did not meet the definition. Children who satisfy the malaria
      and pneumonia clinical definitions need treatment for both disorders. Scarce
      diagnostic methods, especially microscopy, are needed for more specific treatment
      of children with fever and cough.

PMID- 1359220
TI  - Tamoxifen: disease prevention or disease substitution?

PMID- 1359221
TI  - The case for clinical trials of tamoxifen for prevention of breast cancer.

PMID- 1359222
TI  - USA: new AIDS definition.

PMID- 1359223
TI  - Delayed disconnection of dead baby from ventilator.

PMID- 1359224
TI  - HTLV-I transmission from mother to fetus via placenta.

PMID- 1359225
TI  - Detection of HTLV-II in breastmilk of HTLV-II infected mothers.

PMID- 1359226
TI  - PET with fluorine-18 deoxyglucose for pancreatic disease.

PMID- 1359227
TI  - Travellers' diarrhoea associated with cyanobacterium-like bodies.

PMID- 1359228
TI  - Diabetes and schizophrenia: genes or zinc deficiency?

PMID- 1359229
TI  - Screening before hepatitis A vaccination.

PMID- 1359230
TI  - Transmission of hepatitis C by pasteurised factor VIII.

PMID- 1359231
TI  - Antibody-capture particle-adherence test for antibody to HIV-1 in urine.

PMID- 1359232
TI  - Hepatitis C viraemia with normal liver histology in symptomless HIV-1 infection.

PMID- 1359233
TI  - Serological assessment of Helicobacter pylori eradication.

PMID- 1359234
TI  - Beta-cell secretory defect caused by mutations in glucokinase gene.

PMID- 1359235
TI  - Cardiac pacing and breast carcinoma.

PMID- 1359236
TI  - Magnetic resonance imaging in antenatal diagnosis of tuberous sclerosis.

PMID- 1359238
TI  - War injury and post-traumatic morbidity.

PMID- 1359237
TI  - Brain-death and transplantation in Japan.

PMID- 1359239
TI  - Journals for developing countries.

PMID- 1359240
TI  - Clenbuterol and sport.

PMID- 1359241
TI  - Journals for developing countries.

PMID- 1359242
TI  - Journals for developing countries.

PMID- 1359244
TI  - Needlestick injury.

PMID- 1359243
TI  - Training for laparoscopy.

PMID- 1359245
TI  - Needlestick injury.

PMID- 1359246
TI  - Needlestick injury.

PMID- 1359247
TI  - Needlestick injury.

PMID- 1359248
TI  - Simple method for monitoring concentration of inhaled nitric oxide.

PMID- 1359249
TI  - Distinct neurological syndrome in two brothers with hyperuricaemia.

PMID- 1359250
TI  - Acute deterioration of myasthenia gravis after intravenous administration of
      gadolinium-DTPA.

PMID- 1359251
TI  - Malignant histiocytosis in a patient with chronic active Epstein-Barr virus
      infection.

PMID- 1359252
TI  - Atrial fibrillation and cognitive impairment.

PMID- 1359253
TI  - Plasma calcitonin gene-related peptide during gestation.

PMID- 1359254
TI  - Congenital heart lesions, childbirth, and antibiotic prophylaxis.

PMID- 1359255
TI  - Fetal ECG waveform for intrapartum monitoring.

PMID- 1359256
TI  - Aortic distensibility and hypercholesterolaemia.

PMID- 1359257
TI  - Case-fatality rates in severe measles outbreak in rural Germany in 1861.

PMID- 1359258
TI  - Effect of enalapril on myocardial infarction and unstable angina in patients with
      low ejection fractions.
AB  - An association between raised renin levels and myocardial infarction has been
      reported. We studied the effects of enalapril, an angiotensin-converting enzyme
      (ACE) inhibitor, on the development of myocardial infarction and unstable angina
      in 6797 patients with ejection fractions < or = 0.35 enrolled into the two
      Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly
      assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per
      day in two concurrent double-blind trials with the same protocol. Patients with
      heart failure entered the treatment trial (n = 2569) and those without heart
      failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In
      each trial there were significant reductions in the number of patients developing
      myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02;
      prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001;
      355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with
      myocardial infarction compared with 288 in the enalapril group (risk reduction
      23%, 95% CI 11-34%; p < 0.001). 595 placebo group patients developed unstable
      angina compared with 499 in the enalapril group (risk reduction 20%, 95% CI 9
      29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615
      enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths,
      myocardial infarction, and unstable angina was highly significant (20% risk
      reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced
      myocardial infarction, unstable angina, and cardiac mortality in patients with
      low ejection fractions.

PMID- 1359259
TI  - Detection in life of confirmed Alzheimer's disease using a simple measurement of
      medial temporal lobe atrophy by computed tomography.
AB  - The medial temporal lobe of the brain is important for normal cognitive function,
      notably for memory, and is the region with the most extensive pathological change
      in Alzheimer's disease (AD). We wanted to find out if atrophy of the medial
      temporal lobe could be detected in life in patients in whom a diagnosis of AD was
      subsequently established histopathologically. The minimum width of the medial
      temporal lobe, measured by temporal-lobe-oriented computed tomography (CT) about
      one year before death, in 44 patients with a histopathological diagnosis of AD
      (cases) was nearly half (0.56 of the median) that in 75 controls of the same age
      with no clinical evidence of dementia (95% confidence interval 0.51-0.61). There
      was little overlap between the distributions of measurements in cases and
      controls. A cut-off (< 0.79 MoM) selected to yield a 5% false-positive rate gave
      an expected detection rate of 92%. A cut-off selected to yield a false-positive
      rate of 1% (< 0.70 MoM) yielded a 79% detection rate. 20 of the 44 patients with
      histopathologically diagnosed AD had been scanned more than once before death,
      and the test (cut-off < 0.79 MoM) was positive in all 20 more than a year before
      and in 9/10 more than 2 years before death. In 10 subjects with dementia but with
      histopathology excluding AD, the mean minimum width of the medial temporal lobe
      was significantly greater than that in the cases with AD, but was not
      significantly different from that in controls. Medial temporal lobe CT is a non
      invasive, rapid, simple and effective test for AD which could have immediate
      application firstly in improving the accuracy of prevalence and incidence studies
      and, secondly, for the identification of groups of high-risk patients in the
      evaluation of novel treatments for AD. In the future, it could be applied as a
      screening test.

PMID- 1359260
TI  - Pulsed excimer laser versus continuous-wave Nd:YAG laser versus conventional
      angioplasty of peripheral arterial occlusions: prospective, controlled,
      randomised trial.
AB  - Early clinical studies of coronary and peripheral laser angioplasty showed that
      arterial occlusions could be recanalised by continuous-wave lasers delivered with
      contact probes and by pulsed lasers applied with multifibre catheters. However,
      whether laser-assisted angioplasty improves success rates in reopening occlusions
      and in long-term patency rates is unclear. We have compared the primary
      recanalisation and long-term patency rates after laser-assisted and conventional
      percutaneous transluminal angioplasty (PTA) of femoropopliteal artery occlusions
      in 116 consecutive symptomatic patients (excimer laser 37, Nd:YAG laser 40, PTA
      39). Primary recanalisation was achieved in 81 patients (70%). The primary
      recanalisation rate achieved with the excimer laser was significantly lower than
      that with the Nd:YAG laser (49% vs 78%, p < 0.01) or with PTA (82%, p < 0.003).
      The overall angiographic recanalisation rate (primary and secondary
      recanalisation) after laser and PTA was 89%. After 3 months, clinical improvement
      was recorded in 76% of patients. Clinical long-term results were available in 94
      (91%), and angiographic long-term results in 77 (75%), of 103 successfully
      recanalised patients. Life-table analysis of the long-term results revealed no
      significant difference of the restenosis rate between the three treatment groups.
      The 12-month patency rate was 60% as assessed clinically and 39% as judged by
      angiography. Primary and secondary recanalisation rates and long-term patency
      rates were significantly correlated with length of the occlusion. Our results
      suggest that PTA of femoropopliteal artery occlusions is only indicated if the
      occlusion is short (< 8 cm) and that laser-assisted angioplasty should only be
      used after failure of conventional PTA.

PMID- 1359261
TI  - Detection of premature atherosclerosis by high-resolution ultrasonography in
      symptom-free hypopituitary adults.
AB  - Retrospective analysis suggests that there is increased mortality from vascular
      disease in hypopituitary adults, but vascular status before death is unknown.
      High resolution B-mode ultrasonic imaging of both carotid and femoral arteries
      was therefore done in 34 adult hypopituitary patients on routine replacement
      therapy and was compared with that in 39 matched controls. Changes were related
      to risk factors for vascular disease. Carotid intima-media thickness was greater
      in patients than in controls (mean [SD] 0.74 [0.16] vs 0.65 [0.13] mm, p < 0.02).
      This difference was seen in middle-aged and elderly patients. More patients than
      controls had one or more atheromatous plaques (65% vs 41%, p < 0.05). The
      percentage of individual arteries with a plaque was also higher in patients (32%
      vs 18%, p < 0.005). In multiple regression analysis, patients' age was the
      dominant factor determining carotid intima-media thickness. Symptom-free adults
      with hypopituitarism show an increased prevalence of atherosclerosis.

PMID- 1359262
TI  - Ambulatory oxygen in chronic heart failure.
AB  - Ambulatory oxygen therapy may be of benefit in bicycle exercise tests. We have
      assessed the effects of ambulatory oxygen during walk tests in 12 patients with
      chronic heart failure. In 6 min walks with the patient breathing air, mean (SD)
      arterial oxygen saturation (SaO2) fell from 94.4 (3.7)% at rest to 90.1 (6.1)% (p
      = 0.014) on exercise. 21/min oxygen increased resting SaO2 from 93.7 (4.0)% (air
      cylinder) to 96.5 (3.0)% (p < 0.001) with no effect on minimum SaO2, distance, or
      breathlessness. During endurance walks, 4 l/min oxygen increased minimum SaO2
      from 90.4 (5.6)% to 93.5 (4.7)% (p = 0.011) but also had no effect on
      breathlessness or distance. Ambulatory oxygen in currently available cylinders
      cannot be recommended for patients with chronic heart failure.

PMID- 1359263
TI  - Isolation of Helicobacter pylori from human faeces.
AB  - Helicobacter pylori is arguably the commonest chronic infection in man. However,
      its route of transmission is unknown. We have isolated viable H pylori from the
      faeces of an infected individual from The Gambia. The organism was cultured on
      selective media after concentration of faecal bacteria by centrifugation in a
      buffer equilibrated with a microaerophilic gas mixture. Growth characteristics,
      microscopic appearances, and enzyme activities were the same as those of a
      typical gastric isolate of H pylori. Protein preparations derived from the new
      isolate and the typical strain were antigenically similar, and had very similar
      electrophoretic profiles (including two major protein bands of 62 and 26 kDa,
      corresponding to the urease enzyme subunits). With the same technique, organisms
      with the colony morphology, growth requirements, enzyme activities, and
      microscopic appearances of H pylori were isolated from the faeces of 9 of 23
      randomly selected children aged 3-27 months from a Gambian village with a high
      prevalence of H pylori infection in early life. Faecal-oral transmission is
      probably important in the spread of infection in such communities.

PMID- 1359264
TI  - Smoking and decreased fertilisation rates in vitro.
AB  - To examine possible mechanisms for the association between cigarette smoking and
      reduced fertility, we have measured the concentration of the nicotine metabolite
      cotinine in ovarian follicular fluid collected at the time of oocyte recovery
      during treatment for in-vitro fertilisation. In a group of women in whom
      follicular fluid cotinine could not be detected (limit of accurate measurement 20
      ng/ml) 116 oocytes were collected, of which 84 became fertilised (72%), whereas
      among women with cotinine concentration greater than 20 ng/ml 20/45 (44%) oocytes
      did so (p < 0.01). The median fertilisation rates for individuals (range 1-8 eggs
      each) in the high and low cotinine groups were 57% and 75%, respectively (p <
      0.05). These findings suggest that infertile women should be advised to stop or
      reduce smoking generally, and especially before treatment by in-vitro
      fertilisation.

PMID- 1359265
TI  - From cardiac to vascular protection: the next chapter.

PMID- 1359266
TI  - Shaving the head: reason or ritual?

PMID- 1359268
TI  - Chimpanzees in trees do it.

PMID- 1359267
TI  - Changing case-definition for AIDS.

PMID- 1359269
TI  - Success with coronary angioplasty as seen at demonstrations of procedure.
AB  - To assess the real-life results of coronary angioplasty, unidentified
      participants made notes on 104 cases demonstrated live at twelve international
      angioplasty courses in 1991. The initially planned procedure was successful in
      73% with crossover to another device in 20% for an ultimate success rate of 93%.
      Interventions lasted an hour on average and two devices on average were used per
      artery tackled. Rates of success and of complication necessitating reintervention
      were, for balloon angioplasty (57 cases) 81% and 19%, for directional atherectomy
      (16 cases) 75% and 0%, for the Rotablator (12 cases) 42% and 42%, for stent
      implantation (10 cases) 100% and 0%, for excimer laser angioplasty (6 cases) 17%
      and 33%, and for Rotacs recanalisation (3 cases) 67% and 0%, respectively. The
      complications were occlusions (threatened, acute, or delayed) and they were
      usually treated by balloon angioplasty or a stent. No death or myocardial
      infarction was reported. The observer attending the demonstration tended to take
      a less favourable view of the outcome than the clinician doing the procedure and
      in general the results of coronary angioplasty seemed inferior to those reported
      in journals. Interventions done before an audience will be unusually stressful
      but this will be outweighed by the fact that difficult cases with a low
      probability of success are rarely tackled during live courses. This survey
      suggests that conventional balloon angioplasty, complemented by stent
      implantation in selected cases, is the treatment of choice.

PMID- 1359271
TI  - Smoking and statistical overkill.

PMID- 1359270
TI  - Seroepidemiological survey of hepatitis E in Hong Kong by recombinant-based
      enzyme immunoassays.
AB  - The agent that causes the enterally transmitted form of non-A, non-B hepatitis
      has been cloned and called hepatitis E virus (HEV). We have carried out a
      seroepidemiological survey on the prevalence of hepatitis E in Hong Kong. In a
      retrospective study, serum from 394 patients with acute viral hepatitis and 355
      healthy subjects was tested for antibodies to HEV (anti-HEV) with a recombinant
      based enzyme immunoassay. 65 (16.5%) patients with hepatitis were positive for
      IgM anti-HEV and 23 (5.8%) were also positive for IgM anti-HEV. Of 18 patients
      diagnosed as having acute non-A, non-B, non-C hepatitis, 6 were IgM anti-HEV
      positive. 17 (6%) patients in whom acute hepatitis A was diagnosed were also
      infected with HEV. None of 70 patients with acute hepatitis B or C or
      exacerbation of chronic hepatitis B was IgM anti-HEV positive. 57 (16.1%) of the
      healthy subjects were positive for IgG anti-HEV. The prevalence of IgG anti-HEV
      was higher in subjects over 20 years old than in younger subjects (24% vs 4%, p <
      0.0001). IgG anti-HEV was detected in 26% of subjects who were positive for IgG
      antibody to HAV and in 7% of those negative for that antibody (p < 0.0001). We
      demonstrated the validity of the recombinant-based enzyme immunoassays for the
      diagnosis of hepatitis E. Our results suggest that hepatitis E accounts for a
      third of non-A, non-B, non-C hepatitis in Hong Kong and that coinfection of
      hepatitis A and E can occur.

PMID- 1359272
TI  - Countdown to Clinton's first 100 days.

PMID- 1359273
TI  - Canada: controversy over Royal Commission on Reproductive Technologies.

PMID- 1359274
TI  - USA: victory over gag rule for family planning groups.

PMID- 1359275
TI  - USA: therapeutic AIDS vaccine trial debated.

PMID- 1359276
TI  - Germany: new health-care law agreed.

PMID- 1359277
TI  - Europe: review of short-acting benzodiazepines.

PMID- 1359278
TI  - Italy: national health service intact but charges rise.

PMID- 1359279
TI  - Issues in HIV testing in developing countries.

PMID- 1359280
TI  - Cancer and magnetic field.

PMID- 1359281
TI  - Environmental pollution and health.

PMID- 1359282
TI  - Environmental pollution and health.

PMID- 1359283
TI  - Environmental pollution and health.

PMID- 1359284
TI  - Environmental pollution and health.

PMID- 1359285
TI  - Environmental pollution and health.

PMID- 1359286
TI  - Bacterial growth in blood for transfusion.

PMID- 1359287
TI  - Hiccough relief with cisapride.

PMID- 1359288
TI  - Lamotrigine for generalised epilepsies.

PMID- 1359289
TI  - Ondansetron and hyperemesis gravidarum.

PMID- 1359290
TI  - Benzodiazepine sensitivity in Leber's hereditary optic neuroretinopathy.

PMID- 1359291
TI  - Magnesium deficiency and cardiovascular disease.

PMID- 1359292
TI  - Hypergammaglobulinaemia and IgG subclass deficiency.

PMID- 1359293
TI  - Hypergammaglobulinaemia and IgG subclass deficiency.

PMID- 1359294
TI  - Bone-marrow transplantation in sickle-cell anaemia: why so few so late?

PMID- 1359295
TI  - HIV infection and immune system in genesis of coronary lesions.

PMID- 1359296
TI  - Septic shock from Eikenella corrodens and Staphylococcus epidermidis in HIV
      infection.

PMID- 1359297
TI  - Speech arrest as manifestation of seizures in non-ketotic hyperglycaemia.

PMID- 1359298
TI  - Barosaurus and its circulation.

PMID- 1359299
TI  - Barosaurus and its circulation.

PMID- 1359300
TI  - Barosaurus and its circulation.

PMID- 1359301
TI  - Harm done through treatment of childhood cancers.

PMID- 1359302
TI  - Volunteering for research.

PMID- 1359303
TI  - Volunteering for research.

PMID- 1359304
TI  - Bleeding oesophageal varices and transjugular intrahepatic portosystemic
      shunting.

PMID- 1359305
TI  - Acute hepatitis A in haemophiliacs.

PMID- 1359306
TI  - Detection of hepatitis A virus RNA in commercially available factor VIII
      preparation.

PMID- 1359307
TI  - Prevention of suicide.

PMID- 1359308
TI  - Prevention of suicide.

PMID- 1359309
TI  - Prevention of suicide. The Swedish PTD Committee.

PMID- 1359310
TI  - In-utero cystostomy.

PMID- 1359311
TI  - Pain during streptokinase infusion.

PMID- 1359312
TI  - Pain during streptokinase infusion.

PMID- 1359313
TI  - Pain during streptokinase infusion.

PMID- 1359314
TI  - Myocardial evidence of dystrophin mosaic in a Duchenne muscular dystrophy
      carrier.

PMID- 1359315
TI  - Artifactual p53 point mutations: possible effect of gene secondary structure on
      PCR and direct sequence analysis.

PMID- 1359316
TI  - Interferon alfa and development of type 1 diabetes mellitus.

PMID- 1359317
TI  - Randomised comparison of amniocentesis and transabdominal and transcervical
      chorionic villus sampling.
AB  - We have compared three methods of prenatal diagnosis in two large obstetric
      centres in Denmark. Women were randomly assigned transabdominal (TA) chorionic
      villus sampling (CVS), transcervical (TC) CVS, or second-trimester amniocentesis
      (AC); women at high genetic risk were randomised between the two CVS groups only.
      Analysis of 45 epidemiological variables showed the three procedure groups to be
      similar at enrollment. All women were followed up until completion of pregnancy.
      Among 3079 women at low genetic risk total fetal loss rates were 10.9% for TC
      CVS, 6.3% for TA CVS, and 6.4% for AC (p < 0.001). More women had bleeding after
      the procedure in the CVS groups (p < 0.001), whereas more amniotic fluid leakage
      (p < 0.001) was reported after AC. No uterine infections occurred in any group.
      No case of oromandibular-limb abnormality was seen in the CVS groups, but 1 child
      in the AC group had aplasia of the right hand. The two CVS approaches were
      compared among 2882 women at low and high genetic risk who were found to have
      cytogenetically normal fetuses. Rates of unintentional loss after the procedure
      were 7.7% for TC CVS and 3.7% for TA CVS (p < 0.001; 95% Cl of difference 2.3
      5.8%). At baseline ultrasound scanning after establishment of optimum sampling
      conditions, more TC than TA procedures (p < 0.001) were judged not to be
      feasible. We found that TA CVS allows better access to the placental site than TC
      sampling, is an easier skill to acquire, and has the potential that more villi
      can be aspirated when needed. The risk of fetal loss is similar after TA CVS and
      AC. However, losses after AC are at a later stage and are therefore more
      distressing. TA procedures remain the first choice for prenatal diagnosis. Since,
      in our hands, TC sampling carries a greater risk to the fetus, we have abandoned
      TC CVS in our two study centres.

PMID- 1359318
TI  - Comparison of oral artemether and mefloquine in acute uncomplicated falciparum
      malaria.
AB  - Plasmodium falciparum malaria in Thailand is highly resistant to available
      antimalarials, and alternative drugs are needed urgently. Artemether is effective
      against falciparum malaria but associated with a high recrudescence rate. The
      proper dosage regimen remains to be defined. We have done a clinical trial
      comparing mefloquine 1250 mg in divided doses with oral artemether at 700 mg
      total dose given over 5 days in acute uncomplicated falciparum malaria. 46
      patients, admitted to the Bangkok Hospital for Tropical Diseases, were randomised
      to receive either mefloquine (12) or artemether (34). Hospital follow-up was 28
      days for the artemether group and 42 days for the mefloquine group. Oral
      artemether gave a significantly faster parasite clearance time than mefloquine
      (30 vs 64 h), and a significantly better cure rate (97 vs 64%) with fewer
      episodes of dizziness and vomiting. Oral artemether at 700 mg given over 5 days
      is effective and well tolerated. The cure rate with this regimen is higher than
      that reported by previous studies with 600 mg intramuscular artemether given over
      5 days. Oral artemether can be considered as an alternative drug for multiple
      drug-resistant falciparum malaria.

PMID- 1359319
TI  - Protection against bradykinin-induced bronchoconstriction in asthmatic patients
      by neurokinin receptor antagonist.
AB  - Axon reflex mechanisms may be involved in the pathogenesis of asthma, but there
      has been no direct evidence that endogenous tachykinins cause bronchoconstriction
      in asthmatic subjects. We have studied the effect of a tachykinin receptor
      antagonist (FK-224) on bronchoconstriction induced by inhalation of bradykinin in
      asthmatic patients. In a double-blind, placebo-controlled, crossover trial, ten
      subjects with stable asthma were given FK-224 (4 mg) or placebo by inhalation 20
      min before challenge with bradykinin (0-1250 micrograms/ml, five breaths of each
      concentration) given with 5 min intervals. Bradykinin caused dose-dependent
      bronchoconstriction in all subjects. FK-224 significantly opposed the
      bronchoconstrictor effect; the geometric mean of the cumulative concentration
      required to elicit a 35% fall in specific airway conductance was 5.3
      micrograms/ml after placebo and 40 micrograms/ml after FK-224 (p < 0.001).
      Inhalation of bradykinin caused coughing in three subjects, which was inhibited
      by FK-224 in all three. Antagonism of the tachykinin receptor by FK-224 greatly
      inhibited both bronchoconstriction and coughing induced by bradykinin in
      asthmatic patients, suggesting that tachykinin release from the airway sensory
      nerves is involved in responses to bradykinin. Tachykinin receptor antagonists
      may be useful in the treatment of asthma.

PMID- 1359320
TI  - Cross-contamination potential with dental equipment.
AB  - Some types of reused dental equipment, especially handpieces and their
      attachments for drilling and cleaning teeth, might be responsible for cross
      contamination if patient material were to lodge temporarily in difficult-to
      disinfect internal mechanisms. This possibility is worrisome with respect to
      transmission of hepatitis B and human immunodeficiency viruses (HBV, HIV).
      Previous cross-contamination studies have relied on laboratory experiments with
      bacteria or dye tracers. To assess possible risk more thoroughly, we tested 30
      new prophylaxis angles and 12 new high-speed handpieces to see whether they would
      take up and expel contaminants in laboratory and clinical trials. In treatments
      of three patients, including two infected with HIV, human-specific DNA (beta
      globin, HLA DQ alpha) and HIV proviral DNA were detected inside or coming back
      from the devices. Similarly, when handpieces were operated in contact with blood
      pooled from HBV-infected patients, HBV DNA was detected in samples taken from
      inside the equipment and from their attached air/water hoses. When we used
      bacteriophage phi X174 as a model virus in laboratory tests, many infective viral
      particles were recovered from internal mechanisms of handpieces, their connecting
      air/water hoses, and from water spray expelled when the equipment was reused. We
      recommend that reused high-speed, air-driven handpieces and prophylaxis angles
      should be cleaned and heat-treated between patients. Further studies are needed
      to determine ways of eliminating the risks associated with exhaust hoses and
      air/water input lines.

PMID- 1359321
TI  - Cardiotoxicity after accidental herb-induced aconite poisoning.
AB  - Aconitine and its related alkaloids are known cardiotoxins with no therapeutic
      role in modern western medicine. The rootstocks of Aconitum plants, which contain
      aconite alkaloids, have been common components of Chinese herbal recipes. We have
      documented life-threatening intoxication in 17 Chinese subjects after accidental
      herb-induced aconite poisoning. All patients developed symptoms of aconite
      toxicity within 2 h of herb ingestion. Most developed tachyarrhythmias, including
      ventricular tachycardia and fibrillation from which 2 patients died.
      Toxicological evaluation revealed that aconites from the Aconitum rootstocks were
      the only plausible casual factor for intoxication. These cases point to the need
      for strict surveillance of herbal substances with low safety margins.

PMID- 1359322
TI  - Amphotericin versus pentamidine in antimony-unresponsive kala-azar.
AB  - We compared the efficacy of amphotericin B and pentamidine isethionate in a
      prospective randomised trial in 120 uncomplicated and parasitologically confirmed
      cases of antimony-unresponsive kala-azar. Doses were twenty intramuscular
      injections of pentamidine 4 mg/kg on alternate days or fourteen definitive doses
      of amphotericin 0.5 mg/kg infused in 5% dextrose on alternate days. 48 (80%)
      patients given pentamidine showed initial cure and 46 (77%) showed definitive
      cure compared with 60 (100%) and 59 (98%) cases, respectively, on amphotericin (p
      < 0.001). Amphotericin also brought about quicker abatement of fever and more
      complete spleen regression.

PMID- 1359323
TI  - Is clearance of HIV-1 viraemia at seroconversion mediated by neutralising
      antibodies?
AB  - The mechanism of clearance of human immunodeficiency virus-1 (HIV-1) viraemia is
      not fully understood. In two patients with acute HIV-1 infection, initial high
      titres of free infectious virus in plasma declined rapidly to undetectable levels
      within 4-8 weeks, an event that was coincident with seroconversion. Neutralising
      antibodies directed against the first autologous isolates taken during the
      viraemic periods could not be detected in either patient around the time of
      disappearance of plasma virus. In the absence of functional neutralising
      antibody, it is unlikely that humoral factors are responsible for the suppression
      of primary viraemia in early HIV infection.

PMID- 1359324
TI  - Risk of HIV transmission during dental treatment.

PMID- 1359325
TI  - Bile acid therapy in the 1990s.

PMID- 1359326
TI  - Mammography: uncertainty clarified.

PMID- 1359328
TI  - Chariots of fear: wheelchair-related accidents.

PMID- 1359327
TI  - Chronic myeloid leukaemia: potential for antisense therapy.

PMID- 1359329
TI  - Pathogenesis of endometriosis.

PMID- 1359331
TI  - Anal intraepithelial neoplasia: part of a multifocal disease process.
AB  - Invasive carcinomas of the anogenital epithelium share a common aetiological
      factor--human papillomavirus (HPV) type 16. Although genital intraepithelial
      neoplasia may be multifocal, there have been no studies of the prevalence of anal
      intraepithelial neoplasia in women with intraepithelial neoplasia of the genital
      tract. We tested the hypothesis that women with high-grade cervical
      intraepithelial neoplasia are at higher risk of disease in the anus than are
      control women of similar age with no history of anogenital neoplasia. 29 (19%) of
      152 women with cervical intraepithelial neoplasia grade III had histological
      evidence of anal intraepithelial neoplasia. Of the 29 patients, 11 had grade III
      anal lesions; 2 of those women had concomitant invasive anal squamous-cell
      carcinomas. Only 7% (8/115) women with high-grade lesions of the cervix alone had
      evidence of anal intraepithelial neoplasia; by contrast, 57% (21/37) of those
      with more than one focus of intraepithelial neoplasia (cervix plus vulva, vagina,
      or both) had anal lesions. HPV 16 DNA was identified in 18 (51%) of 35 anal
      biopsy samples in the study group. No evidence of anal intraepithelial neoplasia
      was found in the control group (50 women), although 2 patients had grade I
      cervical lesions. HPV 16 DNA was identified in 12 (24%) of biopsy samples from
      the cervix and 7 (14%) from the anus in the control group; all 7 women with anal
      HPV 16 had concomitant cervical infection. The role of anal examination in the
      assessment of women with any focus of genital intraepithelial neoplasia requires
      further investigation.

PMID- 1359330
TI  - Treatment of endometriosis.

PMID- 1359332
TI  - USA: Employer allowed to reduce AIDS patient's health benefit.

PMID- 1359333
TI  - Association between confined placental trisomy, fetal uniparental disomy, and
      early intrauterine growth retardation.

PMID- 1359334
TI  - Uniparental disomy with normal phenotype.

PMID- 1359335
TI  - Computed tomographic angiography for carotid imaging.

PMID- 1359336
TI  - Magnetic resonance imaging in perianal Crohn's disease.

PMID- 1359337
TI  - Analysis of natural history of breast cancer in young women.

PMID- 1359338
TI  - Obstructed defaecation because of adult sacrococcygeal teratoma.

PMID- 1359339
TI  - Death from tetanus in sickle-cell disease.

PMID- 1359340
TI  - Micrometastatic tumour cells in bone marrow in colorectal cancer.

PMID- 1359341
TI  - Liver dysfunction, anaemia, and granulocytopenia after exanthema subitum.

PMID- 1359342
TI  - HHV-6 infection during pregnancy and spontaneous abortion.

PMID- 1359343
TI  - Acute adrenal insufficiency after discontinuation of inhaled corticosteroid
      therapy.

PMID- 1359344
TI  - Economic evaluation of peripheral blood stem cell transplantation for lymphoma.

PMID- 1359345
TI  - Spurious outbreak of HCV in bone-marrow recipients treated with cytomegalovirus
      immunoglobulin.

PMID- 1359346
TI  - Passively transfused hepatitis C antibody.

PMID- 1359347
TI  - Specialty-defined medical curriculum.

PMID- 1359348
TI  - Specialty-defined medical curriculum.

PMID- 1359349
TI  - Specialty-defined medical curriculum.

PMID- 1359350
TI  - "I would like to become a general physician".

PMID- 1359351
TI  - Capitalism in Japan's hospitals.

PMID- 1359352
TI  - Rethinking famine relief.

PMID- 1359353
TI  - Psychological aspects of loin-pain/haematuria syndrome.

PMID- 1359354
TI  - Surveillance for small-for-gestational-age fetuses.

PMID- 1359355
TI  - Energy supplementation during pregnancy and postnatal growth.

PMID- 1359356
TI  - Energy supplementation during pregnancy and postnatal growth.

PMID- 1359357
TI  - Duration of anticoagulation for deep-vein thrombosis and pulmonary embolism.

PMID- 1359358
TI  - Duration of anticoagulation for deep-vein thrombosis and pulmonary embolism.

PMID- 1359359
TI  - Duration of anticoagulation for deep-vein thrombosis and pulmonary embolism.

PMID- 1359360
TI  - Effect of thrombolytic treatment delay on myocardial infarct size.

PMID- 1359361
TI  - Reverse passive haemagglutination test for identification and serotyping of
      polioviruses.

PMID- 1359362
TI  - Acute renal failure after overdose of colloidal bismuth subcitrate.

PMID- 1359363
TI  - The Leicester anti-vaccination movement.

PMID- 1359364
TI  - Heterogeneity of high affinity uptake of L-glutamate and L-aspartate in the
      mammalian central nervous system.
AB  - Characteristics of high affinity uptake of L-glutamate are examined in order to
      evaluate the possible use of the uptake of [3H]L-glutamate, [3H]L-aspartate or
      any other suitable [3H]-labelled substrate as a marker for glutamatergic and
      aspartergic synapses in autoradiographic studies in the mammalian brain. Review
      of data on substrate specificity indicates the presence of at least two high
      affinity uptake systems specific for acidic amino acids in the central nervous
      tissue; one which takes up L-glutamate and L-aspartate and the other which is
      selective for L-glutamate only. Studies on ionic requirements, too, point to the
      existence of at least two distinct uptake systems with high affinity for L
      glutamate. The Na(+)-dependent uptake system(s) handle(s) both L-glutamate and L
      aspartate whereas the Na(+)-independent uptake system(s) show(s) selectivity for
      L-glutamate only. Available data do not favour the Na(+)-dependent binding of
      [3H]D-aspartate to thaw-mounted sections of frozen brain tissue as a suitable
      marker for glutamatergic/aspartergic synaptic nerve endings. However, there are
      reasons--such as the results of lesion studies and the existence of uptake sites
      which have a higher affinity for L-aspartate than for D-aspartate--to suggest
      that Na(+)-dependent binding of [3H]L-aspartate, rather than that of [3H]D
      aspartate, should be further investigated as a possible marker for the
      glutamatergic/aspartergic synapses in the autoradiographic studies using sections
      of frozen brain.

PMID- 1359365
TI  - An antibody to dopamine D2 receptor inhibits dopamine antagonist and agonist
      binding to dopamine D2 receptor cDNA transfected mouse fibroblast cells.
AB  - A polyclonal antibody to dopamine D2 receptor (D2-receptor) has been used to
      examine the immuno-inhibition in the binding of a D2 antagonist, [3H]YM09151-2
      and an agonist, PPHT-fluorescein to dopamine receptor DNA transfected mouse
      fibroblast cells. The specific activity of the [3H]YM09151-2 binding to
      transfected (Ltk-RGB) cells is 4-5 fold higher than untransfected (Ltk-) cells.
      The antibody is able to inhibit the [3H]YM09151-2 binding to the cell membranes
      from Ltk-RGB cells (Bmax 110.56 +/- 5.26 and 76.20 +/- 5.18 fmoles/mg protein in
      the presence of preimmune and immune sera, respectively, with no change in the
      Kd). The flow cytometric analysis of the PPHT-fluorescein labeled Ltk- and Ltk
      RGB cells indicated that ligand specific fluorescence is associated only with
      small Ltk-RGB cells (second peak) and autofluorescence with large cells (first
      peak). Preincubation of the Ltk-RGB cells with antibody, reduced the fluorescence
      intensity of the PPHT-fluorescein by 20-25% without changing the auto
      fluorescence. These results suggest that peptide antibody recognize D2-receptor
      in both membranes and in intact cells and interact at or near the ligand binding
      site of the receptor.

PMID- 1359366
TI  - The effect of amperozide, a new antipsychotic drug, on plasma corticosterone
      concentration in the rat.
AB  - Amperozide is an atypical antipsychotic drug with high affinity for the serotonin
      5-HT2 receptor but with low affinity for the dopamine D1 and D2 receptors.
      Amperozide dose-dependently increased the level of plasma corticocorticosterone
      in the rat. The effect of amperozide on plasma corticosterone was not inhibited
      by pretreatment with the 5-HT1A receptor antagonist pindolol or the 5-HT2
      receptor antagonist ritanserin. Nor was it inhibited by the dopamine D2 receptor
      antagonist haloperidol. In contrast to ritanserin, amperozide did not antagonize
      plasma corticosterone elevation elicited by the serotonin receptor agonist MK
      212. Similar to the serotonin uptake inhibitor fluoxetine, amperozide (0.5 mg/kg)
      significantly (p < 0.05) blocked p-chloroamphetamine (PCA) induced corticosterone
      release 4 and 16 hrs after amperozide administration. However, amperozide
      significantly increased the plasma corticosterone concentration also in rats
      pretreated with parachlorophenylalanine (PCPA). These data suggest that other
      mechanisms than a 5-HT uptake inhibitory effect are involved in the acute
      stimulation of corticosterone by amperozide.

PMID- 1359367
TI  - Opposite influence of medial preoptic D1 and D2 receptors on genital reflexes:
      implications for copulation.
AB  - Dopamine D1 and D2 receptors may synergize with or oppose each other's effects.
      We suggest that stimulation of D1 and D2 receptors in the medial preoptic area
      (MPOA) of male rats have opposing effects on genital reflexes. In Experiment 1 a
      D1 agonist injected into the MPOA increased the number of ex copula erections but
      decreased the number of seminal emissions. In Experiment 2 a D1 antagonist had
      the opposite effects (decreased erections and increased seminal emissions), as
      had a D2 agonist previously. We also suggest that D1 and D2 mechanisms in the
      MPOA have different thresholds of activation. In Experiment 3 a low dose of the
      mixed D1/D2 agonist apomorphine increased erections and anteroflexions, an effect
      blocked by the D1 antagonist. In Experiments 3 and 4 a high dose of apomorphine
      increased seminal emissions, an effect blocked by the D2 antagonist. Thus, low
      levels of dopaminergic stimulation may facilitate erections and anteroflexions
      (controlled by the parasympathetic system and striated muscles) via D1 receptors;
      higher or more prolonged stimulation may shift to seminal emission (controlled by
      the sympathetic system) via D2 receptors. This may explain the progression from
      erectile to ejaculatory mechanisms during copulation.

PMID- 1359368
TI  - The neurochemistry of depression: evidence derived from studies of post-mortem
      brain tissue.

PMID- 1359369
TI  - GABAA receptor function and regional analysis of subunit mRNAs in long-sleep and
      short-sleep mouse brain.
AB  - The greater sensitivity of long-sleep (LS), as compared with short-sleep (SS),
      mice to ethanol is due in part to differences in GABAA receptor function in
      specific brain regions. To determine if differences in subunit composition of
      GABAA receptors contribute to this differential sensitivity, we measured alpha 1
      and gamma 2 subunit mRNAs with Northern analysis and in situ hybridization and
      gamma 2S, gamma 2L and alpha 6 subunit mRNAs with polymerase chain reaction (PCR)
      amplification. No differences in mRNAs in whole brain were apparent by Northern
      analysis. In situ hybridization revealed that alpha 1 and gamma 2 subunit mRNAs
      were co-localized in many brain regions but that they still had distinct patterns
      of hybridization. However, the few differences observed between LS and SS mice in
      the levels of hybridization for these subunits did not show a regional
      distribution consistent with ethanol sensitivity differences. Similar ratios of
      gamma 2L, and gamma 2S subunit mRNAs were found in LS and SS mouse cerebral
      cortex and hippocampus, and both mouse lines expressed essentially only gamma 2L
      subunit mRNA in cerebellum. mRNA for the alpha 6 subunit was detected only in
      cerebellum and also was qualitatively similar between LS and SS mice. Studies of
      muscimol-stimulated 36Cl- uptake by cortical membrane vesicles confirmed earlier
      findings that ethanol does not enhance function of GABAA receptors in SS mice
      when assayed at 30 degrees C. However, at 34 degrees C ethanol did increase this
      function in SS mice although the enhancement remained greater in LS mice. These
      functional results, together with the results showing similar levels of alpha 1,
      gamma 2S, gamma 2L and alpha 6 subunits in LS and SS mice, suggest that the
      ethanol-insensitivity of SS mouse GABAA receptors cannot be due solely to lack of
      subunits required for ethanol action and further suggest that differences in
      catalytic mechanisms affecting post-translational processing may account for some
      genetic differences in ethanol sensitivity of GABAA receptors.

PMID- 1359370
TI  - Age-dependent regulation of GABAA receptors in neocortex.
AB  - We have shown previously that GABAA receptors labelled with the antagonist
      [3H]SR95531 can be regulated in a living cortical slice preparation by agonists
      or changes in electrical activity. Due to the important role that receptor
      regulation may play in controlling neural activity, we have now investigated the
      regulation of GABAA receptors in neocortex at different stages in postnatal life.
      We found that regulation by agonist stimulation and increases in bioelectric
      activity is age-dependent in amount and, in the latter case, in direction. Using
      muscimol as an agonist we observed a GABAA receptor down-regulation of between 60
      and 70% at 20-30 days of age; in adults muscimol gave an 11% down-regulation. A
      combination of veratridine and glutamate gave a peak down-regulation of 39% at 20
      days postnatal, but an up-regulation of 58% in adults. These age-dependent
      effects may signal a role for receptor regulation in cortical neural critical
      period plasticity.

PMID- 1359371
TI  - Molecular cloning and primary structure of the avian Thy-1 glycoprotein.
AB  - We have previously characterised, both biochemically and immunohistochemically, a
      23 kDa putative avian Thy-1 protein homologue. In this report we have examined
      the carbohydrates present on the protein and determined the partial protein
      sequence of enzymatically and CNBr-produced peptides. The protein sequences
      enabled us to clone an essentially full-length (1854 bp) cDNA using PCR and
      colony screening of an embryonic day (ED) 18 forebrain pUEX-1 cDNA library.
      Analysis of deduced amino acid sequence shows the 23 kDa protein to be 110 amino
      acids in length compared to mouse (112) and human and rat (111) while still
      retaining the conserved cysteine residues. The N-glycosylation site at position
      61 is the same as that in the human protein, but is different from that in the
      rodent (position 75). Northern blot analysis of Thy-1 mRNA expression in the
      forebrain, cerebellum and tectum show that all three tissues have low levels at
      ED4 (forebrain and tectum) and ED8 (cerebellum), rising most rapidly between ED16
      and the first few days post-hatch. Analysis of various tissues at hatch and adult
      show expression to be predominantly neuronal with very low levels in some other
      organs, mainly at hatch, indicating the possibility of subsets of cells, which we
      have also seen in histological sections, in these tissues expressing Thy-1 mRNA.
      Bone marrow and blood cells were also negative for Thy-1 protein.

PMID- 1359372
TI  - VILIP, a cognate protein of the retinal calcium binding proteins visinin and
      recoverin, is expressed in the developing chicken brain.
AB  - Using a selective cloning approach we previously isolated a number of cDNAs of
      transcripts that are newly expressed during terminal differentiation of the
      chicken optic tectum. Here, we have characterized one of these cDNAs (OZ1) by
      Northern analysis and in situ hybridization. The OZ1 cDNA hybridizes to two
      transcripts of 1.6 kb and 2.9 kb which are widely expressed in the brain but not
      detectable in liver, heart or skeletal muscle. Cloning of overlapping cDNAs
      revealed that both transcripts encode the same open reading frame for a
      polypeptide of 191 amino acids. The deduced protein contains 4 EF-hand consensus
      motifs characteristic of calmodulin-like Ca(2+)-binding proteins. It displays 40%
      and 46% sequence identity with the retinal photoreceptor-specific Ca(2+)-binding
      proteins visinin and recoverin, respectively, and was termed VILIP (visinin-like
      protein). VILIP transcripts are also expressed in the retina. However, the
      expression pattern does not overlap with that of visinin or recoverin. The
      possible functional implications of the similarity to recoverin, which regulates
      guanylate cyclase activity of retinal rod cells in a Ca(2+)-dependent manner, are
      discussed.

PMID- 1359373
TI  - A human dopamine transporter cDNA predicts reduced glycosylation, displays a
      novel repetitive element and provides racially-dimorphic TaqI RFLPs.
AB  - We describe a cDNA for the human dopamine transporter, which has been implicated
      in several human disorders linked to dopaminergic function. The cDNA predicts
      reduced glycosylation of the protein with respect to the rat transporter, as well
      as a novel repetitive element in the 3' untranslated region of the cDNA. A TaqI
      RFLP is also reported that shows a race-specific difference in allelic
      frequencies.

PMID- 1359374
TI  - Alterations in mRNA of enkephalin, dynorphin and thyrotropin releasing hormone
      during amygdala kindling: an in situ hybridization study.
AB  - The present study examined changes in mRNA expression of various neuropeptides at
      several stages of amygdala kindled seizures. 35S-labelled oligonucleotide probes
      for mRNA of enkephalin (ENK), dynorphin (DYN) and thyrotropin releasing hormone
      (TRH) were hybridized to brain sections of rats sacrificed 24 h after a stage 1
      or stage 5 seizure, or 2 weeks after a stage 5 seizure. Changes in expression
      developed as kindling progressed, with long-lasting changes in ENK and transient
      changes in DYN and TRH. ENK mRNA levels increased in pyriform and entorhinal
      cortices at stage 1 and 5 and remained elevated in the pyriform two weeks after a
      stage 5 seizure. In contrast, DYN mRNA was decreased bilaterally in the dentate
      gyrus 24 h after a stage 5 seizure, but returned to control levels two weeks
      after a stage 5 seizure. TRH mRNA was dramatically increased 24 h after a stage 1
      or stage 5 seizure. After a stage 1 seizure two patterns developed. One showed
      increases in the pyriform, entorhinal and perirhinal cortices ipsilateral to the
      stimulation. The other pattern displayed bilateral increases in the dentate gyrus
      with or without the unilateral increases the limbic cortices. Twenty-four hours
      after a stage 5 seizure, large bilateral increases were found in these areas, but
      these returned to baseline levels by two weeks after a stage 5 seizure. The data
      demonstrate a constellation of alterations in several peptide systems with
      distinct spatiotemporal patterns, particularly in regions known to be important
      in kindling and epilepsy, such as the dentate gyrus and pyriform and entorhinal
      cortices. The relationship of these neuropeptide mRNA changes to those previously
      found in c-fos mRNA expression during the development of kindling is discussed.

PMID- 1359375
TI  - Characterization and regulation of a high affinity [3H]CNQX labelled AMPA
      receptor in rat neocortex.
AB  - We have characterized a high affinity site of the alpha-amino-3 hydroxy-5-methyl
      isoxazole-4-propionate (AMPA) receptor in in vitro living slices of adult rat
      neocortex using [3H]CNQX, and AMPA antagonist. [3H]CNQX labelled multiple binding
      sites with a Bmax of a high affinity site of approximately 470 fmol/mg protein
      and an apparent Kd of 11.3 nM. The high affinity site of the AMPA receptor could
      be down-regulated (36%) by 2 h preincubations in quisqualate, an AMPA agonist.
      Increases in electrical activity induced by a combination of veratridine and
      glutamate also led to an average decrease of the high affinity AMPA receptor
      number of 17%. In addition, preincubations with muscimol, a GABAA agonist, as
      well as glutamate agonists kainate and N-methyl-D-aspartate (NMDA) led to an
      average increase in high affinity AMPA receptor number of 17%, 14%, and 37%,
      respectively. The present results show that a ligand-gated high affinity AMPA
      receptor can be regulated by agonist stimulation as well as changes in neural
      activity.

PMID- 1359376
TI  - Parallel upregulation of catecholamine-synthesizing enzymes in rat brain and
      adrenal gland: effects of reserpine and correlation with immediate early gene
      expression.
AB  - Changes in the mRNA levels of all catecholamine-synthesizing enzymes were
      examined 24 h after a single injection of reserpine by in situ hybridization. The
      responses of the midbrain dopaminergic cells in the ventral tegmental area and
      substantia nigra compacta, locus ceruleus and adrenal gland were studied in three
      groups of animals receiving either no injection, vehicle injection or reserpine
      10 mg/kg subcutaneously. Increases in enzyme message signal observed by in situ
      hybridization were corroborated by Northern blot analysis for all four enzyme
      mRNAs species expressed in the locus ceruleus and adrenal gland were found while
      no change of enzyme message was detected the midbrain. Two distinct
      subpopulations of adrenomedullary cells could be distinguished by their baseline
      levels of enzyme mRNA expression: the majority of medullary cells have moderate
      adrenomedullary cells could be distinguished by their baseline levels of enzyme
      mRNA expression: the majority of medullary cells have moderate levels of all four
      enzyme mRNAs but a minority of cells show very high signal for the first three
      enzymes of the catecholamine synthesis pathway. To test whether reserpine elicits
      a selective transcriptional response of the catecholamine enzyme genes or induces
      other neuronal genes, cDNA probes for the growth-associated protein GAP-43 which
      is highly expressed and neurofilament L which is weakly expressed in
      monoaminergic neurons were used as independent cellular markers and showed no
      change in message levels. Changes in mRNA levels of the proto-oncogenes c-fos and
      c-jun were examined 1 h after injection of reserpine by in situ hybridization and
      compared to the pattern observed for the Fos protein immunohistochemically. C-fos
      and c-jun proto-oncogene activation was observed 1 h after reserpine in the locus
      ceruleus and adrenal medulla, specifically in those catecholaminergic structures
      that respond with increased enzyme gene transcription; in contrast, the
      dopaminergic neurons of the substantia nigra did not exhibit detectable proto
      oncogene activation, only a small group of neurons in the ventral tegmental area
      showed c-fos without concomitant c-jun expression after reserpine.

PMID- 1359377
TI  - Effects of arch height of the foot on ground reaction forces in running.
AB  - There is a suggested link between running injuries and arch type of the foot.
      However, a distinct cause and effect relationship has not been established. Feet
      may be functionally categorized on the basis of arch height. The purpose of this
      study was to compare selected ground reaction force variables in running for
      different arch heights. Static height of the medial longitudinal arch was
      measured using a caliper, arch flattening during running was determined by video
      analysis, and ground reaction forces during running were recorded from a KISTLER
      force plate. Thirty-four subjects were divided into three arch height and three
      arch flattening groups, and single-factor analyses of variance were conducted to
      compare the groups. Arch height and arch flattening were not found to be
      significantly related. However, the initial medial force peak in the low arch
      group occurred significantly later than in the normal and high arch groups, and
      the anterior force peak in the low flattening group was lower compared with the
      medium and high flattening groups (P < 0.05). Both arch measurements were
      ineffective in accounting for the observed variability in the ground reaction
      forces in running. Specifically, the impact forces did not differ for the
      different arch height and arch lowering groups.

PMID- 1359378
TI  - Dissociation of macrophage cytolysis and ability to transfer anti-listeria
      resistance by concanavalin A-stimulated spleen cells.
AB  - In this study, we determined whether spleen cells from Listeria monocytogenes
      immunized mice were cytolytic for Listeria-infected macrophages. Spleen cells
      freshly obtained from immunized donors were unable to lyse Listeria-infected
      macrophages unless they were first stimulated in vitro for 2-3 days with
      Concanavalin A (ConA) or L. monocytogenes. Spleen cells from non-immunized mice
      developed cytolytic activity after incubation with ConA, but not with L.
      monocytogenes. Cytolytic spleen cells demonstrated an equivalent ability to lyse
      uninfected and Listeria-infected thioglycollate elicited peritoneal macrophages.
      Maximal cytolysis required co-incubation of effector and target cells for 18-20
      h. Spleen cell culture supernatants did not lyse macrophages, suggesting that
      cytolysis required direct contact. Preincubation of immune spleen cells with ConA
      decreased their ability to transfer anti-listeria resistance in the spleens, but
      not the livers of recipient mice. Depletion of CD4+ or CD8+ cells did not
      significantly reduce the ability of ConA-incubated Listeria-immune spleen cells
      to transfer resistance. Despite being cytolytic for Listeria-immune infected
      macrophages, ConA-stimulated non-immune spleen cells did not transfer anti
      listeria resistance. These results indicate that cytolytic cells can be generated
      by short-term incubation of spleen cells with antigen or mitogen. The
      dissociation between in vitro cytolytic activity and ability to transfer
      protection, however, suggests that the two biological activities are not
      inextricably linked.

PMID- 1359379
TI  - Characterization and detection of the 40 kDa fimbrial subunit of Bacteroides
      fragilis BE1.
AB  - The amino acid composition and amino-terminal amino acid sequence of the 40 kDa
      fimbrial subunit of Bacteroides fragilis were determined. No similarity with
      other known fimbrial subunits or protein sequences was found. The isoelectric
      point of the fimbriae was determined to be 3.8. The acidic nature of these
      fimbriae is in agreement with the amino acid composition of the fimbrial subunit.
      An IgM monoclonal antibody, raised against the denaturated subunit of strain BE1
      fimbriae, reacted with native BE1 fimbriae and appeared to be strain specific.
      Bacteroides fragilis strain BE38 expressed fimbriae which did not react with the
      polyclonal or monoclonal antibodies directed against strain BE1 fimbriae.

PMID- 1359380
TI  - Binding of Haemophilus ducreyi to extracellular matrix proteins.
AB  - A collection of Haemophilus ducreyi isolates were screened for the ability to
      bind to fibrinogen, fibronectin, collagen, gelatin and laminin by a particle
      agglutination test using latex beads coated with the individual proteins.
      Thirteen of 21 isolates reacted with all five extracellular matrix proteins.
      Binding of organisms to protein-coated latex beads was inhibited by pretreatment
      of the bacteria with detergent, trypsin or boiling. Two isolates did not bind to
      collagen and gelatin with one of these not reacting with laminin either. Seven
      strains which failed to react with laminin did not express pili when examined by
      electron microscopy. This observation suggests a specific interaction with the
      pili of H. ducreyi.

PMID- 1359381
TI  - Bacterial spinal epidural abscess. Review of 43 cases and literature survey.
AB  - We have reviewed our experience with 43 cases of bacterial spinal epidural
      abscess, as well as previously reported series of cases. We found a striking male
      predominance of the disease, accounting for 86% of cases. Most patients had some
      underlying conditions that predisposed to infection, a prior infection at a
      distant site, or an abnormality or trauma to the spine. Presenting symptoms
      included backache (72%), radicular pain (47%), weakness of an extremity (35%),
      sensory deficit (23%), bladder or bowel dysfunction (30%), and frank paralysis
      (21%). Patients cared for in public hospitals tended to seek medical attention in
      later stages of the disease than patients admitted to private hospitals. Spinal
      epidural abscess was the suspected diagnosis in only 40% of the cases; the
      remainder of the time various other infections, tumors, neurologic diseases, or
      degenerative conditions were considered. Patients in whom the diagnosis of spinal
      epidural abscess was not initially entertained on admission suffered delays in
      diagnosis and experienced neurologic deterioration. Staphylococcus aureus was the
      predominant pathogen (65%) and was associated with positive blood cultures in
      nearly every case; aerobic or facultative gram-negative bacilli were next most
      common. Coagulase-negative staphylococci caused infection only in patients who
      had previous spinal instrumentation. Although analysis of CSF was abnormal in the
      majority of cases, abnormalities were nonspecific, Gram stain was always negative
      and culture was rarely diagnostic. Abscesses extended over an average of 4
      vertebrae, and the majority were located in the lumbar region followed by
      thoracic and cervical regions. Unlike previous series, we noted an equal
      frequency of anterior and posterior epidural abscesses; although differences were
      not statistically significant, posterior abscesses tended to be more extensive
      but less commonly associated with radiographic abnormalities of osteomyelitis.
      Myelography revealed an abnormality in every case in which it was done.
      Computerized tomographic scanning after intrathecal injection of contrast
      material always provided additional useful information. Even though magnetic
      resonance imaging was diagnostic in only 4 of 5 cases (80%) in our series, this
      test is noninvasive and clearly delineates the location and nature of spinal
      lesion. It should, therefore, probably replace myelography as an initial
      definitive study in patients suspected of having spinal infection. Plain
      roentgenograms and nuclear scans contributed little useful information that was
      not already available from other radiographic procedures. Surgical drainage
      together with antibiotics was the treatment of choice; 35 of our 43 patients
      underwent operative intervention. The preoperative status clearly predicted the
      final neurologic outcome.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1359382
TI  - Consecutive actions of different gene-altering mechanisms in the evolution of
      involucrin.
AB  - During the evolution of primates from nonprimates, the gene for involucrin was
      greatly altered by changes in the short tandem repeats that are present in some
      form in the gene of each of 17 species examined. The evolution of involucrin was
      not the result of a single continuum of more or less random changes, and it was
      not confined to the process of nucleotide substitution, the most commonly studied
      evolutionary change in DNA. Instead, the evolution of this gene took place
      through different mechanisms that shortened the length of the repeats, increased
      their number, and changed their codon sequence. As part of this trend, one entire
      segment of repeats was replaced by another located elsewhere in the coding
      region. To bring about these changes, specific mechanisms have been activated,
      deactivated, and replaced by other mechanisms. The resulting serial revisions in
      the involucrin gene must depend on gene-altering machinery whose synthesis or
      activity can be controlled.

PMID- 1359383
TI  - [A case of unusual occupational allergy to bee venom].
AB  - The authors discuss an exceptional case of allergy to bee venom in a zoo
      technician working on a morphological analysis of bees. During her work, the zoo
      technician was repeatedly stung, initially with only small local reaction. After
      six-year period of work, the symptoms that followed stinging had all the
      characteristics of general oedema. Next years of exposure to bee venom resulted
      in collapse in the patient. Allergological examinations indicated work-related
      hypersensitivity to bee venom. The case history was supplemented with
      prophylactic recommendations. General principles of controlling the shock were
      provided.

PMID- 1359384
TI  - Surface exclusion specificity of the TraT lipoprotein is determined by single
      alterations in a five-amino-acid region of the protein.
AB  - The TraT protein is a highly cell-surface-exposed lipoprotein specified by F-like
      plasmids that confers serum resistance and blocks the conjugative transfer of
      plasmids to cells bearing identical or closely related plasmids, a process known
      as surface exclusion. The TraT protein specified by the antibiotic-resistance
      plasmid R6-5 was purified to apparent homogeneity. When added to mating mixtures,
      TraT blocked the transfer of plasmids belonging to Surface Exclusion Group IV
      (Sfx IV) but had no significant effect on the transfer of plasmids belonging to
      other groups. Additionally, the purified protein has a protective effect on
      bacterial cells incubated in serum, indicating that it does not have to be
      located on the cell surface to mediate serum resistance. To localize regions of
      the protein that were responsible for surface exclusion specificity, the amino
      acid sequence of the TraT protein specified by CoIB2-K98 (Sfx II) was determined
      by cloning and sequencing of the corresponding gene. Comparison of the derived
      sequence with those of the F and R100-1 proteins indicated that surface exclusion
      specificity of TraT is determined by single alterations in a five-amino-acid
      region (residues 116-120). This was confirmed by segment swapping experiments in
      which the specificity of the R6-5 TraT protein (Sfx IV) was switched to that of
      the CoIB2-K98 protein (Sfx II). Our results suggest that the region defined by
      residues 116-120 is located on the external face of the outer membrane and
      interacts specifically with the donor cell in surface exclusion.

PMID- 1359385
TI  - Characterization and functional expression in Escherichia coli of the
      sodium/proton/glutamate symport proteins of Bacillus stearothermophilus and
      Bacillus caldotenax.
AB  - The genes encoding the Na+/H+/L-glutamate symport proteins of the thermophilic
      organisms Bacillus stearothermophilus (gltTBs) and Bacillus caldotenax (gltTBc)
      were cloned by complementation of Escherichia coli JC5412 for growth on glutamate
      as sole source of carbon, energy and nitrogen. The nucleotide sequences of the
      gltTBs and gltTBc genes were determined. In both cases the translated sequences
      corresponded with proteins of 421 amino acid residues (96.7% amino acid identity
      between GltTBs and GltTBc). Putative promoter, terminator and ribosome-binding
      site sequences were found in the flanking regions. These expression signals were
      functional in E. coli. The hydropathy profiles indicate that the proteins are
      hydrophobic and could form 12 membrane-spanning regions. The Na+/H+ coupled L
      glutamate symport proteins GltTBs and GltTBc are homologous to the strictly H+
      coupled L-glutamate transport protein of E. coli K-12 (overall 57.2% identity).
      Functional expression of glutamate transport activity was demonstrated by uptake
      of glutamate in whole cells and membrane vesicles. In accordance with previous
      observations (de Vrij et al., 1989; Heyne et al., 1991), glutamate uptake was
      driven by the electrochemical gradients of sodium ions and protons.

PMID- 1359386
TI  - Alcohol delays clearance of lipoproteins from the circulation.
AB  - Long-term (18-month) consumption of high-dose ethanol ([EtOH] 24% of total
      calories) by squirrel monkeys results in marked elevations in plasma
      antiatherogenic high-density lipoprotein (HDL) cholesterol and apolipoprotein
      (apo) A-1, and atherogenic low-density lipoprotein (LDL) cholesterol and apo B.
      In an effort to determine whether alterations in lipoprotein turnover could
      explain the above findings, 131I-HDL apo A-1 and 125I-LDL apo B were injected
      into EtOH and control animals, following which in-vivo catabolic and production
      rates were determined. For both lipoproteins, synthetic rates were unaltered,
      while fractional catabolic rates (FCR) were significantly reduced in EtOH
      monkeys. Results from this study implicate EtOH-induced changes in hepatic
      metabolism as the basis for delayed lipoprotein clearance and hence elevated
      plasma apolipoprotein levels.

PMID- 1359387
TI  - Synthesis of a yohimbine-agarose matrix useful for large-scale and
      micropurification of multiple alpha 2-receptor subtypes.
AB  - We have provided a detailed protocol for the synthesis of a yohimbine-agarose
      matrix that has been shown to be effective for isolation of the alpha 2A
      adrenergic receptor from human platelet and purification of the alpha 2A
      adrenergic receptor to apparent homogeneity from porcine brain cortex using
      chromatography on only two sequential yohimbine-agarose columns. In addition,
      this affinity matrix also interacts with alpha 2 receptors of the alpha 2B
      subtype extracted from cultured NG108-15 cells. Finally, this affinity matrix has
      proven useful for monitoring posttranslational modifications of the receptor in
      digitonin extracts of metabolically labeled cells. Thus, this affinity matrix can
      be exploited for the purification of multiple alpha 2-adrenergic receptor
      subtypes on both a macro- and microscale and should be of value to any laboratory
      exploring the molecular basis for alpha 2-adrenergic functions.

PMID- 1359388
TI  - [The surface structures and biological properties of Klebsiella strains].
AB  - The electron-microscopic method has been used to study the surface structures and
      biological properties (adhesiveness, antibiotic-resistance, biochemical
      properties) in 67 strains of Klebsiella isolated from one-year-old children with
      intestinal infections (56) and from healthy ones (11). It is found that bacterial
      cells in 58.2% of strains have fimbriae of the 3d type, in 20.9%--of the 1st
      type. No correlation has been revealed between the type of fimbriae and the
      studied properties.

PMID- 1359389
TI  - Recent developments in the pharmacotherapy of cardiac failure.

PMID- 1359390
TI  - Follow-up care after acute myocardial infarction.
AB  - OBJECTIVE: To examine the medical care received by patients following discharge
      from hospital after acute myocardial infarction (AMI). SETTING AND DESIGN:
      Community-based cross-sectional survey. PATIENTS: 2836 consecutive patients aged
      25-64 years living in the Perth Statistical Division who were admitted to
      hospital with AMI during 1984-1988. After one reminder the response rate was 71%.
      RESULTS: Half of all respondents were in full-time employment at the time of
      their AMI. At follow-up this had fallen to a third. Over 80% of patients visited
      a cardiologist after AMI, with half remaining under consultant care to the time
      of survey. However, one in five patients reported no follow-up care at the time
      of survey. Seventy-three per cent of patients reported undergoing at least one
      exercise stress test after AMI, with 61% undergoing angiography, 16% angioplasty
      and 24% coronary bypass surgery. Large proportions of the patients accurately
      reported being prescribed beta-blockers and antiplatelet agents. The pattern of
      prescribing at discharge corresponded closely with the use of cardioactive agents
      at the time of survey and with drugs reported to have been taken continuously
      since discharge to the time of survey. CONCLUSIONS: These data suggest that
      follow-up care after AMI is both comprehensive and widespread. Such care may have
      contributed significantly to the overall decline in mortality from ischaemic
      heart disease.

PMID- 1359391
TI  - Research perspectives in heritable disorders of connective tissue.

PMID- 1359392
TI  - [Bloodsucking mosquitoes on the irrigated lands of Kara-Kalpakia. I. The species
      composition and distribution of mass species].
AB  - Data on fauna of bloodsucking mosquitos (Culicidae), obtained during the survey
      in the irrigated part of Takhta-Kupyr District of Kara-Kalpakia in 1988-1989, are
      presented. The density of mosquito populations of mass species in different parts
      of the oasis is, to a great extent, caused by the presence of reservoirs of
      different types and also by the features of anthropogenic landscapes.

PMID- 1359393
TI  - [The results and problems of surgical treatment of cancer of the duodenal papilla
      of Vater].
AB  - Twenty six of 28 cases (92.9%) of cancer of duodenal papilla of Vater were
      resected from 1981 to 1990. Twenty five pancreatoduodenectomy and one total
      pancreatectomy were performed. Operative death and hospital death were not
      observed. Three year and five year cumulative survival rates of resected cases
      were 58% and 52% respectively. There was relatively good correlation between
      pathological cancer extension and postoperative prognosis. Postoperative
      prognosis of the cases which had cancer extension to the pancreas was extremely
      poor. But the prognosis of the cases of cancer within Oddi muscle was extremely
      good. Immunohistochemical staining using anti CEA, anti CA19-9 and anti DUPAN 2
      was studied and Grade III staining pattern was observed only in the cases which
      had cancer invasion to the pancreas. Preoperative diagnosis of cancer extension
      using endoscopic ultrasonography and appropriate choice of the operative
      procedure are important. Extended operation and effective adjuvant therapy are
      necessary for advanced cases of cancer of the duodenal papilla.

PMID- 1359394
TI  - Cloning and mapping of telomere-associated sequences from Hordeum vulgare L.
AB  - We present a novel approach to the efficient cloning of telomere-associated
      sequences and demonstrate its application to the cloning and mapping of these
      sequences from barley. The method is a modification of the Vectorette PCR
      technique and allows specific amplification and cloning of subtelomeric
      sequences. Telomere-associated sequences isolated from barley include
      hypervariable, repetitive sequences. Polymorphisms detected by subtelomeric
      markers behaved as Mendelian factors and were mapped to the most distal positions
      of barley chromosomes 1, 2, and 4.

PMID- 1359395
TI  - kappa-Opioid inhibition of [3H]dopamine release from rat ventral mesencephalic
      dissociated cell cultures.
AB  - The present study investigated the effect of opioids on [3H]dopamine release from
      mixed neuronal-glial cell cultures of embryonic rat ventral mesencephalon. Each
      of the major morphological types of dopaminergic cell was represented in these
      cultures. These cells exhibited specific uptake of [3H]dopamine, which was
      subsequently released, in a calcium-dependent manner, in response to a double
      pulse of elevated extracellular potassium. Spontaneous and potassium-evoked
      [3H]dopamine release was inhibited by kappa- but not mu- or delta-opioid
      agonists. The selective kappa 1 agonist (5 alpha, 7 alpha, 8 beta)-(-)-N-methyl-N
      [7-(1-pyrollidinyl)-1-oxaspiro(4,5)- dec-8-yl]benzeneacetamide (U69593) produced
      a dose-dependent inhibition of dopamine release. The effect of U69593 was blocked
      by the nonselective opiate antagonist naloxone and the selective kappa opioid
      antagonist norbinaltorphimine. kappa-Opioid inhibition of potassium-evoked
      [3H]dopamine release was maintained in the presence of tetrodotoxin. These
      results suggest that functional kappa receptors, modulating dopamine release, are
      localized on the terminals of dopaminergic neurons.

PMID- 1359396
TI  - Coexisting beta 1- and atypical beta-adrenergic receptors cause redundant
      increases in cyclic AMP in human neuroblastoma cells.
AB  - In SK-N-MC human neuroblastoma cells, the cAMP response to 10 nM isoproterenol
      (ISO) is mediated primarily by beta 1-adrenergic receptors. However, responses to
      higher concentrations of ISO (100-1000 nM) were only weakly blocked by beta 1-
      and beta 2-selective antagonists. When beta 1 receptors were blocked with 10
      microM CGP 20712A, catecholamines still maximally activated cAMP accumulation,
      with only small decreases in potency. In the presence of CGP 20712A, beta
      blockers inhibited the response to ISO stereoselectively but with relatively low
      potencies. Pindolol derivatives were partial agonists with low potencies, and the
      atypical agonist BRL 37344 was a partial agonist with an intermediate potency.
      All binding sites in these cells labeled by 125I-cyanopindolol were of the beta 1
      subtype. Nuclease protection assays indicated that SK-N-MC cells contain mRNA for
      both the human beta 1- and beta 3-adrenergic receptors, with the beta 3 subtype
      mRNA being expressed 25-50% more abundantly than that for the beta 1 subtype.
      Northern blot hybridizations showed the presence of two beta 3 mRNA transcripts
      of 3.1 and 2.4 kilobases. These results suggest that beta 1- and atypical beta
      adrenergic receptors coexist in these cells and cause redundant increases in cAMP
      formation. Although molecular approaches suggest that the atypical subtype is the
      beta 3, the observed drug specificity differs from that reported for the
      expressed recombinant human beta 3 receptor.

PMID- 1359397
TI  - Unsurmountable antagonism of brain 5-hydroxytryptamine2 receptors by (+)-lysergic
      acid diethylamide and bromo-lysergic acid diethylamide.
AB  - Lysergic acid diethylamide (LSD) and its structural analogue 2-bromo-lysergic
      acid diethylamide (BOL) act as unsurmountable antagonists of serotonin-elicited
      contractions in smooth muscle preparations. Two different models, allosteric and
      kinetic, have been invoked to explain these findings. The present studies
      investigate the mechanism of antagonism of brain 5-hydroxytryptamine (5HT)2
      receptors, utilizing cells transfected with 5HT2 receptor cDNA cloned from rat
      brain. A proximal cellular response, phosphoinositide hydrolysis, was examined in
      order to minimize possible postreceptor effects. Even though LSD behaved as a
      partial agonist and BOL as a pure antagonist, both drugs blocked the effect of
      serotonin in an unsurmountable manner, i.e., increasing concentrations of
      serotonin could not overcome the blocking effect of LSD or BOL. Radioligand
      binding studies showed that preincubation of membranes with either LSD or BOL
      reduced the density of [3H]ketanserin binding sites, suggesting that the drugs
      bind tightly to the 5HT2 receptor and are not displaced during the binding assay.
      Two additional experiments supported this hypothesis. First, the off-rate of [3H]
      LSD was slow (20 min), relative to that of [3H]ketanserin (approximately 4 min).
      Second, when the length of incubation with [3H]ketanserin was increased to 60
      min, the LSD-induced decrease in Bmax was essentially eliminated. The possibility
      that LSD and BOL decrease [3H]ketanserin binding by interacting with an
      allosteric site was rejected, because neither drug altered the rate of
      dissociation of [3H]ketanserin. The most parsimonious interpretation of these
      results is that unsurmountable antagonism reflects prolonged occupancy of the
      receptor by slowly reversible antagonists.

PMID- 1359398
TI  - Long term treatment with desipramine increases the turnover of alpha 2
      adrenoceptors in the rat brain.
AB  - The aim of this study was to quantitate the turnover of alpha 2-adrenoceptors in
      different regions of the rat brain and its modulation during desipramine (a
      cyclic antidepressant drug)-induced receptor down-regulation. The recovery of
      [3H]clonidine (a mixed alpha 2A/B-adrenoceptor agonist) binding after
      irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline
      (EEDQ) (an alkylating agent for both alpha 2-adrenoceptor subtypes) was assessed
      in control and desipramine-treated (3 mg/kg, intraperitoneally, every 12 hr for 7
      35 days) rats to study the process of alpha 2-adrenoceptor repopulation and to
      calculate receptor turnover parameters. In control rats, the turnover of brain
      alpha 2-adrenoceptors showed marked regional differences. The fastest receptor
      turnover rate was found in the hypothalamus and corpus striatum (receptor half
      life, t1/2 = 2.1 days), compared with that in the brainstem (t1/2 = 2.6 days),
      cerebral cortex (t1/2 = 3.9 days), and hippocampus (t1/2 = 4.3 days). In the
      cerebral cortex and other brain regions, desipramine induced a time-dependent
      modulation of alpha 2-adrenoceptors, with significant decreases in the number of
      receptors (40-71%; p < 0.01) during the first 7-14 days of treatment and
      regulation to base-line values by 21-35 days. In the cerebral cortex, alpha 2
      adrenoceptor turnover evaluated during desipramine-induced receptor down
      regulation (phase of 7-14 days of treatment) revealed an increase in both the
      disappearance (degradation) (delta k = 122%; p < 0.05; t1/2 = 1.7 days) and
      appearance (synthesis) (delta r = 68%; p < 0.05) rates of the receptor. In other
      noradrenergic brain regions (hippocampus, brainstem, and hypothalamus) but not in
      the corpus striatum, desipramine (7-14 days) also increased alpha 2-adrenoceptor
      degradation (delta k = 97-144%) and shortened the half-life of the receptor, and
      it tended to increase the rate of synthesis (delta r = 51-83%). Similar results,
      but with a higher appearance rate, were obtained in the cerebral cortex during
      the phase of treatment (21-35 days) without apparent receptor down-regulation
      (delta k = 160%; p < 0.01; t1/2 = 1.5 days; delta r = 128%; p < 0.001). It is
      proposed that sustained stimulation of alpha 2-adrenoceptors by endogenous
      norepinephrine, after inhibition of neuronal uptake, increases their
      disappearance rate (degradation), leading to a reduction in receptor number. The
      increase in the appearance (synthesis) rate could be viewed as a later
      compensatory mechanism that would lead to restoration of brain alpha 2
      adrenoceptor density.

PMID- 1359399
TI  - Regulation of tyrosine hydroxylase gene transcription rate and tyrosine
      hydroxylase mRNA stability by cyclic AMP and glucocorticoid.
AB  - Tyrosine hydroxylase mRNA is induced in rat pheochromocytoma PC18 cells by cAMP
      analogs and glucocorticoids. Previous studies have shown that these increases in
      tyrosine hydroxylase mRNA are due at least in part to stimulation of the tyrosine
      hydroxylase gene. However, the involvement of post-transcriptional mechanisms in
      the regulation of tyrosine hydroxylase mRNA by these inducing agents has not been
      investigated. In the present study, using nuclear run-on assays we show that the
      relative transcription rate of the tyrosine hydroxylase gene is stimulated 2-5
      fold within 20 min after treatment of PC18 cells with cAMP analogs or
      dexamethasone and that the rate of transcription remains elevated 2-3-fold for at
      least 24 hr in the continual presence of these inducing agents. Pulse-labeling
      experiments using 4-thiouridine indicate that the rate of synthesis of tyrosine
      hydroxylase mRNA is increased approximately 3-fold or 10-fold after treatment
      with either a cyclic AMP analog or dexamethasone, respectively. These increases
      in rates of synthesis agree well with the fold increases in tyrosine hydroxylase
      mRNA levels after treatment with these inducers. Treatment of the cells with
      cycloheximide lowers the basal relative transcription rate of the tyrosine
      hydroxylase gene 2-3-fold; however, the relative transcription rate of the
      tyrosine hydroxylase gene is still elevated in cells treated with either
      dexamethasone or cAMP analogs in the presence of cycloheximide, compared with the
      transcription rate of the gene in cells treated with cycloheximide alone. These
      results indicate that protein synthesis is not required for the short term
      regulation of the gene by these inducing agents. The apparent t1/2 for tyrosine
      hydroxylase mRNA has been estimated by two different procedures, approach to
      steady state kinetics and pulse-chase analysis. Both procedures yield an
      estimated apparent t1/2 of approximately 6-9 hr for tyrosine hydroxylase mRNA
      under basal culture conditions. Dexamethasone does not substantially alter this
      apparent t1/2 value; however, cAMP appears to lower this apparent t1/2 value
      transiently. Our results suggest that cAMP and glucocorticoid regulate tyrosine
      hydroxylase mRNA levels primarily by stimulating the transcription rate of the
      tyrosine hydroxylase gene; however, cAMP may also regulate the stability of the
      mRNA for a short period of time, such that it is induced more rapidly in the
      cells.

PMID- 1359400
TI  - An extended developmental study of gamma-glutamyltranspeptidase in rat liver
      plasma membranes: identification of specific patterns of changes in activity in
      the adult as well as the neonatal state.
AB  - Homogenates and plasma membranes were isolated from the livers of male Fischer
      344 rats ranging in age from 19 hr to 92 days postnatal. These plasma membranes
      exhibited comparable levels of purity: protein yields were 2-2.5%; relative
      specific activities of 5'-nucleotidase and ouabain-sensitive Na+/K(+)-ATPase were
      from 8-11 and from 12-19, respectively. 5'-nucleotidase and ouabain-sensitive Na+
      K(+)-ATPase displayed distinct and different developmental patterns. The activity
      of gamma-glutamyltranspeptidase was found to be at exceptionally high levels in
      isolated plasma membranes immediately after birth and to decline precipitously
      thereafter achieving and maintaining low levels from days 3-21 postnatal. Liver
      plasma membrane gamma-glutamyltranspeptidase activity was observed to increase
      9.2 fold from this low point, first rising on day 21, peaking on day 40 and
      returning to low levels by day 56. From day 56 day to 92 postnatal, gamma
      glutamyltranspeptidase activity was expressed at a uniformly low level but a
      level 2 fold higher than that preceding the rise at day 40. The hormone
      determinants of these developmental changes in gamma-glutamyltranspeptidase
      activity are discussed.

PMID- 1359401
TI  - Regulation of an H-ras-related transcript by parathyroid hormone in rat
      osteosarcoma cells.
AB  - The rat osteosarcoma cell line UMR 106-01 is a commonly used model system for the
      study of osteoblast function. However, it also expresses a phenotype
      characteristic of transformed cells. To test whether the latter could be
      accounted for by aberrant oncogene expression, we probed Northern blots of UMR
      and other osteoblastic cells with a panel of oncogene probes. These blots, when
      probed with a cDNA specific for v-H-ras, revealed a 7.0-kilobase (kb) H-ras
      related transcript (designated HRRT) in UMR 106-01 cells that was not expressed
      in other osteoblastic cells. Osteoblast-enriched calvarial cells expressed the
      typical 1.1-kb H-ras mRNA, which was absent in UMR cells. Additionally, Western
      blots of lysates of UMR cells documented the presence of three proteins
      immunologically related to H-rasp21. To determine whether HRRT represented a
      recombinant retrovirus product, Northern blots were probed with a cDNA specific
      for the highly conserved gag-pol region of Moloney murine leukemia virus. These
      blots showed parallel cross-reactivity with an apparently identical transcript of
      7.0 kb. The 7.0-kb transcripts detected by both v-H-ras and gag-pol probes
      declined to the same extent after treatment with concentrations of PTH known to
      inhibit proliferation of these cells. PTH regulated the abundance of HRRT in a
      time- and dose-dependent manner, with greatest repression of the transcript after
      8 h of treatment with 10(-8) M PTH. The decrease in HRRT could not be completely
      accounted for by changes in transcriptional activity, as determined by nuclear
      run-on assays.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359402
TI  - The immune response evokes up- and down-modulation of beta 2-adrenergic receptor
      messenger RNA concentration in the male rat thymus.
AB  - Important alterations of noradrenergic activity are known to occur in specific
      brain regions and in different lymphoid tissues during the course of an immune
      response. Our recent characterization of the beta 2-adrenergic receptor (beta
      2AR)-cAMP system of the rat thymus gland, the identification of a thymic beta 2AR
      gene expression, and the marked modulation of receptor mRNA concentration after
      castration and replacement with estrogen prompted us to study the ability of
      products of immune axis activation to modulate beta 2AR number, distribution, and
      expression in the male rat thymus. Moreover, the effect of adrenergic stimulation
      of adenylyl cyclase activity on thymus gland membrane preparations was measured.
      The beta 2AR present in the rat thymus undergoes marked changes in both number
      and distribution during the course of an immune response. At 3 days after
      antigenic challenge (injection of BSA in complete Freund's adjuvant), a sharp
      decrease of receptor number coupled with a significant loss of the
      autoradiographic reaction in the medullary compartment of the rat thymus gland
      were observed. These effects were followed by a significant increase in receptor
      density and number without changes in receptor affinity at 7 and 15 days post
      immunization, corresponding to the pick of the immune response. Parallel
      alterations in adenylyl cyclase activity were measured. Northern blot analysis,
      using a human beta 2AR cDNA as a probe, revealed dramatic alterations of the beta
      2AR mRNA in the thymus, characterized by an approximately 75% decrease of mRNA
      level 3 days after immunization, and by a progressive increase at 7 and 15 days,
      with beta 2AR mRNA concentration rising to levels even higher than those found in
      control animals. These results suggest that the immune response evokes marked
      alterations of the thymic beta 2AR-cAMP signaling pathway. Moreover, antigenic
      stimulation triggers a down- and up-modulation of beta 2AR gene expression.
      Although it is presently unknown whether factor(s) released by immune axis
      activation act at the level of gene transcription to modulate adrenergic receptor
      function in the rat thymus, such down- and up-regulation of beta 2AR mRNA may
      play a role in the dynamic regulation of the immune response.

PMID- 1359403
TI  - [Atypical cat eye syndrome. Fluorescence in situ hybridization of metaphase
      chromosomes].
AB  - In 1983, a chromosome analysis was carried out in a newborn preterm infant with
      minor anomalies (preauricular skin tag, maldescensus testis). All analysed
      metaphases showed a small extra chromosome, which was symmetric, dicentric and bi
      satellited. In spite of in depth analysis, its origin remained obscure. Recent re
      evaluation using fluorescence in situ hybridization (FISH) led to the diagnosis
      of a dicentric chromosome 22. The FISH technique is an important new tool in
      chromosome diagnostics. The phenotype of this infant only vaguely resembles the
      cat eye syndrome. The syndrome should be diagnosed clinically and not only based
      on the results of chromosome analysis.

PMID- 1359404
TI  - [Discovery of the gene makes the direct molecular genetic diagnosis of Martin
      Bell syndrome possible].
AB  - FORMULATION OF QUESTION: In 1991 four independent groups of geneticists succeeded
      in replacing the comparatively unreliable cytogenetic and indirect molecular
      diagnostics of the X-linked Martin-Bell-syndrome (MBS) by a more accurate
      approach. METHODS AND RESULTS: Fine structure analysis of the disease locus at Xq
      27.3 led to the discovery of the fragile X mental retardation gene I (FMR I
      gene), the mutative changes of which are responsible for the disease and can
      easily be detected in Southern hybridizations with gene probes out of this area.
      The observed changes are strong amplification of a repetitive CGG-motive in exon
      I of the gene in patients, a more moderate one in symptom-free carriers of the
      disease and changes in the promotor region of the gene to a varying extent in
      patients and carriers. CONCLUSION: This direct molecular diagnosis of MBS enables
      a safe identification of patients and carriers of the disease. A combined
      analysis of the observed mutations makes possible prenatal diagnosis,
      discriminating between carriers with and without symptoms. Especially this is
      necessary, since 20% of male and 50 to 70% of female mutation carriers are
      phenotypically normal.

PMID- 1359405
TI  - [Treatment of juvenile spondylarthritis and reactive arthritis with
      sulfasalazine].
AB  - Eleven children suffering from juvenile spondylitis and reactive arthritis not
      responding to antiinflammatory therapy were treated with sulfasalazine. Eight
      patients showed good response, in two patients no improvement was seen and in one
      therapy was stopped because of side effects. This overall successful result of
      sulfasalazine therapy of juvenile spondylitis should encourage clinicians to plan
      controlled trials.

PMID- 1359406
TI  - [2nd Three Country Symposium. Switzerland - Germany - Austria. Current themes in
      infant nutrition. Phosphorus and calcium in infant nutrition. Zurich, 17 May
      1991].

PMID- 1359407
TI  - Human Cancer: From Precurable to Curable. Commemorating the 65th birthday of Dr.
      James F. Holland. New York, May 29, 1990.

PMID- 1359408
TI  - Primary sequences of two P-glycoprotein genes of Entamoeba histolytica.
AB  - Two P-glycoprotein genes (EhPgp1 and EhPgp2) from the protozoan parasite
      Entamoeba histolytica were sequenced from a genomic library made with the DNA of
      an emetine-resistant ameba mutant, which overexpresses mRNAs homologous to
      segments of the human mdr1 (P-glycoprotein) gene. The open reading frames for
      EhPgp1 and EhPgp2 were 1302 and 1310 amino acids long, respectively, and showed a
      67% positional identity with each other and 41% and 40% positional identities,
      respectively, with human mdr1 gene. Within each ameba P-glycoprotein were the ATP
      binding sites found twice in eukaryotic P-glycoproteins and once in prokaryotic
      transport proteins. Hydropathy plots of the ameba P-glycoproteins were nearly
      superimposable on that of the human mdr 1, showing 2 homologous halves, each
      containing an ATP-binding site and 6 hydrophobic transmembrane domains that form
      the putative channel. A phylogenetic tree showed that the Entamoeba P
      glycoproteins are more related to the human and mouse P-glycoproteins than to the
      Plasmodium and Leishmania P-glycoproteins. Also identified in the E. histolytica
      genomic library were 2 P-glycoprotein pseudogenes, each with a frame shift and
      stop codons in identical places within the amino ATP-binding site. In conclusion,
      the 2 E. histolytica P-glycoproteins encoded by the EhPgp1 and EhPgp2 genes are
      similar in structure to the mammalian P-glycoproteins and so may be involved in
      energy-dependent drug efflux by this human parasite.

PMID- 1359409
TI  - Stable amplification of a linear extrachromosomal DNA in mycophenolic acid
      resistant Leishmania donovani.
AB  - Pulsed field gel electrophoretic analysis of chromosomes of MPA100 cells, a
      strain of Leishmania donovani that possesses an approx. 15-fold amplified IMP
      dehydrogenase (IMPDH) gene copy number, revealed a new 280-kb extrachromosomal
      DNA, IMPDH-280, that was not present in wild type parental cells. Southern blots
      of these pulsed field gels revealed that the vast majority of the amplified impdh
      genes were localized on IMPDH-280. In addition to the 700-kb wild type
      chromosome, the impdh probe also recognized a 740-kb chromosome in the MPA100
      genome. The pulse time-dependent relative mobility of IMPDH-280 in pulsed field
      gels, the failure of limited gamma-irradiation to generate a new discrete DNA
      fragment, and the susceptibility of IMPDH-280 to lambda-exonuclease digestion,
      demonstrated that IMPDH-280 was a linear molecule. IMPDH-280 was also recognized
      by a telomere probe but not by fragments derived from amplified DNAs found in
      other drug-resistant Leishmania. IMPDH-280 and the drug resistance phenotype
      remained stable when MPA100 cells were propagated in the absence of drug for 2
      years. The appearance of IMPDH-280 in MPA100 cells represents one of the first
      examples of an amplification of a linear extrachromosomal DNA element mediating
      drug resistance in Leishmania and the first instance of a linear DNA
      amplification that is stable in the absence of selective pressure.

PMID- 1359410
TI  - Toxoplasmosis of the central nervous system in the acquired immunodeficiency
      syndrome.
AB  - BACKGROUND AND METHODS: Toxoplasmosis is the most common opportunistic infection
      of the central nervous system in patients with the acquired immunodeficiency
      syndrome (AIDS). To investigate its clinical course, we reviewed the records of
      115 patients with AIDS and central nervous system toxoplasmosis treated at San
      Francisco General Hospital between 1981 and 1990. RESULTS: The most common
      presenting symptoms were headache (in 55 percent), confusion (52 percent), and
      fever (47 percent). Focal neurologic deficits were present in 79 patients (69
      percent). The median CD4 cell count at presentation was 50 per cubic millimeter
      (50 x 10(6) per liter). Thirteen of 80 patients with clinical toxoplasmosis (16
      percent) and 4 of 18 patients with pathologically proved disease (22 percent) had
      undetectable antitoxoplasma IgG antibodies by indirect immunofluorescence assay.
      Of 103 patients, 94 (91 percent) had enhancing lesions on CT. Single lesions were
      seen in 28 of 103 patients (27 percent) on CT, and such lesions were seen in 3 of
      21 patients (14 percent) on magnetic resonance imaging. Over 90 percent of
      patients who eventually had clinical and radiographic improvement had evidence of
      improvement by day 14 of therapy. Adverse drug reactions occurred in 71 patients
      (62 percent) and led to a change in therapy in 50 patients (43 percent). Among
      the patients who survived a first episode of toxoplasmosis, the median survival
      was 265 days. CONCLUSIONS: Toxoplasmosis occurs in advanced stages of human
      immunodeficiency virus infection, and the absence of antitoxoplasma antibodies on
      immunofluorescence assay does not exclude the diagnosis. The clinical and
      radiographic response to therapy is usually rapid, but treatment is frequently
      limited by adverse drug effects.

PMID- 1359412
TI  - Anaphylactic reactions to food.

PMID- 1359411
TI  - Clinical manifestations and predictors of disease progression in drug users with
      human immunodeficiency virus infection.
AB  - BACKGROUND AND METHODS: To examine the clinical course of human immunodeficiency
      virus (HIV) infection in injection-drug users, we conducted a prospective study
      of a cohort of patients in a methadone-treatment program in New York City from
      July 1985 through December 1990. The patients underwent standardized evaluations
      at base line and semiannually thereafter and received on-site primary medical
      care. Rates of progression to the acquired immunodeficiency syndrome (AIDS) and
      major outcomes before the development of AIDS were examined by univariate
      analyses; the risk of AIDS was also assessed by product-limit survival analysis
      and proportional-hazards regression. RESULTS: Of 318 HIV-seropositive patients
      who did not yet have AIDS (171 men and 147 women), 90 were black, 179 were
      Hispanic, and 49 were white; the median age was 33 years. Over a median of 3.0
      years of follow-up, 55 (17 percent) received a diagnosis of AIDS (incidence per
      100 person-years, 5.8). Major outcomes before the development of AIDS included
      oral candidiasis (incidence per 100 person-years, 11.2), pyogenic bacterial
      infections including pneumonia and sepsis (8.0), pulmonary tuberculosis (1.2),
      multiple constitutional symptoms (13.6), and herpes zoster (1.3). There were 41
      deaths from AIDS, and 13 seropositive patients without AIDS (4.1 percent) died of
      bacterial infections, as compared with only 1 of 411 seronegative patients
      studied (P < 0.001). The incidence of AIDS was 62 percent lower among those who
      took zidovudine than among those who did not (P = 0.02). In the multivariate
      analysis, progression to AIDS was best predicted by low numbers and percentages
      of CD4+ lymphocytes, nonuse of zidovudine, and the presence of oral candidiasis,
      bacterial infections, or tuberculosis. There was no consistent relation between
      progression to disease and the continued use of injection drugs. CONCLUSIONS: HIV
      infected injection-drug users have progression to AIDS at rates comparable to
      those of other HIV-infected groups, but they have substantial pre-AIDS morbidity
      and mortality, particularly from bacterial infections, which also appear to
      predict disease progression.

PMID- 1359413
TI  - The cardiac arrhythmia suppression trial.

PMID- 1359414
TI  - Phylogenetic relationships of the genera Arthroderma and Nannizzia inferred from
      mitochondrial DNA analysis.
AB  - The phylogenetic relationship of the genera Arthroderma and Nannizzia, was
      investigated by mitochondrial DNA analysis based on the restriction-fragment
      length polymorphisms. Phylogenetic trees made on ten species. A. benhamiae, A.
      insingulare, A. quadrifidum, A. simii, A. vanbreuseghemii, N. fulva, N. grubyia,
      N. gypsea, N. incurvata and N. otae showed no definite distinctions between the
      genera Arthroderma and Nannizzia. These results support the conclusion of
      Weitzman et al. that the genera Arthroderma and Nannizzia are congeneric.

PMID- 1359415
TI  - Neurological outcome in infants exposed to stimulants in the perinatal period.

PMID- 1359416
TI  - Self-administration of stimulants and serotonergic systems.

PMID- 1359417
TI  - Assessment of new medications for stimulant abuse treatment.

PMID- 1359418
TI  - Cocaine-antagonist effects of limited-efficacy D1 agonists.

PMID- 1359419
TI  - Potential effects of benzodiazepines on cocaine reinforcement in rats.

PMID- 1359420
TI  - Progress report from the Testing Program for Stimulant and Depressant Drugs
      (1990).

PMID- 1359421
TI  - Progress report from the Testing Program for Stimulant and Depressant Drugs
      (1991).

PMID- 1359422
TI  - Human genome project. Variation is now the theme.

PMID- 1359423
TI  - Homeotic transformation of the occipital bones of the skull by ectopic expression
      of a homeobox gene.
AB  - Murine Hox genes have been postulated to play a role in patterning of the
      embryonic body plan. Gene disruption studies have suggested that for a given Hox
      complex, patterning of cell identity along the antero-posterior axis is directed
      by the more 'posterior' (having a more posterior rostral boundary of expression)
      Hox proteins expressed in a given cell. This supports the 'posterior prevalence'
      model, which also predicts that ectopic expression of a given Hox gene would
      result in altered structure only in regions anterior to its normal domain of
      expression. To test this model further, we have expressed the Hox-4.2 gene more
      rostrally than its normal mesoderm anterior boundary of expression, which is at
      the level of the first cervical somites. This ectopic expression results in a
      homeotic transformation of the occipital bones towards a more posterior phenotype
      into structures that resemble cervical vertebrae, whereas it has no effect in
      regions that normally express Hox-4.2. These results are similar to the homeotic
      posteriorization phenomenon generated in Drosophila by ectopic expression of
      genes of the homeotic complex HOM-C (refs 7-10; reviewed in ref. 3).

PMID- 1359424
TI  - Neurotransmission. A retrograde step forward.

PMID- 1359425
TI  - Positive feedback of glutamate exocytosis by metabotropic presynaptic receptor
      stimulation.
AB  - Glutamate is important in several forms of synaptic plasticity such as long-term
      potentiation, and in neuronal cell degeneration. Glutamate activates several
      types of receptors, including a metabotropic receptor that is sensitive to trans
      1-amino-cyclopenthyl-1,3-dicarboxylate, coupled to G protein(s) and linked to
      inositol phospholipid metabolism. The activation of the metabotropic receptor in
      neurons generates inositol 1,4,5-trisphosphate, which causes the release of Ca2+
      from intracellular stores and diacylglycerol, which activates protein kinase C.
      In nerve terminals, the activation of presynaptic protein kinase C with phorbol
      esters enhances glutamate release. But the presynaptic receptor involved in this
      protein kinase C-mediated increase in the release of glutamate has not yet been
      identified. Here we demonstrate the presence of a presynaptic glutamate receptor
      of the metabotropic type that mediates an enhancement of glutamate exocytosis in
      cerebrocortical nerve terminals. Interestingly, this potentiation of glutamate
      release is observed only in the presence of arachidonic acid, which may reflect
      that this positive feedback control of glutamate exocytosis operates in concert
      with other pre- or post-synaptic events of the glutamatergic neurotransmission
      that generate arachidonic acid. This presynaptic glutamate receptor may have a
      physiological role in the maintenance of long-term potentiation where there is an
      increase in glutamate release mediated by postsynaptically generated arachidonic
      acid.

PMID- 1359426
TI  - Tumorigenesis. Suppression with a difference.

PMID- 1359427
TI  - Universal cellular tropism?

PMID- 1359428
TI  - Mutations in T-cell antigen receptor genes alpha and beta block thymocyte
      development at different stages.
AB  - Analysis of mice carrying mutant T-cell antigen receptor (TCR) genes indicates
      that TCR-beta gene rearrangement or expression is critical for the
      differentiation of CD4-CD8- thymocytes to CD4+CD8+ thymocytes, as well as for the
      expansion of the pool of CD4+CD8+ cells. TCR-alpha is irrelevant in these
      developmental processes. The development of gamma delta T cells does not depend
      on either TCR-alpha or TCR-beta.

PMID- 1359429
TI  - Molecular characterization of the Arabidopsis floral homeotic gene APETALA1.
AB  - The first step in flower development is the transition of an inflorescence
      meristem into a floral meristem. Each floral meristem differentiates into a
      flower consisting of four organ types that occupy precisely defined positions
      within four concentric whorls. Genetic studies in Arabidopsis thaliana and
      Antirrhinum majus have identified early-acting genes that determine the identify
      of the floral meristem, and late-acting genes that determine floral organ
      identity. In Arabidopsis, at least two genes, APETALA1 and LEAFY, are required
      for the transition of an influorescence meristem into a floral meristem. We have
      cloned the APETALA1 gene and here we show that it encodes a putative
      transcription factor that contains a MADS-domain. APETALA1 RNA is uniformly
      expressed in young flower primordia, and later becomes localized to sepals and
      petals. Our results suggest that APETALA1 acts locally to specify the identity of
      the floral meristem, and to determine sepal and petal development.

PMID- 1359430
TI  - Are vertebrate exons scanned during splice-site selection?
AB  - Pairwise recognition of splice sites as a result of a scanning mechanism is an
      attractive model to explain the coordination of vertebrate splicing. Such a
      mechanism would predict a polarity-of-site recognition in the scanned unit, but
      no evidence for a polarity gradient across introns has been found. We have
      suggested that the exon rather than the intron is the unit of recognition in
      vertebrates and that polyadenylation and splicing factors interact during
      recognition of 3'-terminal exons. Interaction is reflected in maximal rates of in
      vitro polyadenylation. If scanning across the exon is operating during this
      interaction, then insertion of a 5' splice site should depress polyadenylation.
      Here we report recognition in vitro and in vivo of a 5' splice site situated
      within a 3'-terminal exon, and a concomitant depression of polyadenylation and
      ultraviolet crosslinking of a polyadenylation factor. Decreased crosslinking was
      only found when the 3' and 5' splice sites were within 300 nucleotides of each
      other. These results are consistent with an exon scanning mechanism for splice
      site selection.

PMID- 1359432
TI  - [2d congress of the European Society of Contraception, Athens 6-9 May 1992].

PMID- 1359431
TI  - Evidence from guinea-pig trachealis that Uptake2 of isoprenaline is enhanced by
      hyperpolarization of the smooth muscle.
AB  - Previous studies (Bonisch et al. 1985; Trendelenburg 1986, 1987) have provided
      evidence that Uptake2 of catecholamines is inhibited by depolarization of cells.
      The aim of this study was to further examine the relationship between Uptake2 and
      membrane potential by testing the hypothesis that Uptake2 is, conversely,
      stimulated by hyperpolarization of cells. The effects of beta-adrenoceptor
      agonists (isoprenaline and salbutamol) and beta-adrenoceptor antagonists
      (propranolol and ICI 118,551) on Uptake2 of isoprenaline were examined in guinea
      pig trachealis muscle, in which stimulation of beta-adrenoceptors mediates
      hyperpolarization of the smooth muscle cells (Allen et al. 1985), and in rat
      heart, in which beta-adrenoceptor agonists do not cause hyperpolarization. In
      guinea-pig trachealis muscle segments, propranolol and ICI 118,551 reduced
      Uptake2 (as measured by the steady-state rate of corticosterone-sensitive
      formation of 3-O-methylisoprenaline normalized for the isoprenaline
      concentration) in tissues incubated in 2.5-250 nmol/l 3H-isoprenaline (in the
      range over which isoprenaline causes hyperpolarization of the muscle), but not in
      1 nmol/l 3H-isoprenaline (which does not hyperpolarize the muscle). The
      normalized rates were greater in tissues incubated in 25 nmol/l than 1 nmol/l
      isoprenaline, and were enhanced by 2.5 mumol/l salbutamol in tissues incubated in
      1 nmol/l isoprenaline. In rat hearts perfused with 1 or 25 nmol/l 3H-isoprenaline
      and U-0521 to inhibit catechol-O-methyltransferase, the rate of Uptake2 of
      isoprenaline, normalized for the isoprenaline concentration, was unaffected by
      the isoprenaline concentration or the presence of propranolol, ICI 118,551 or
      salbutamol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359433
TI  - [Effects of short-term application of glutamate-containing solution on isolated
      rat hippocampal neurons].
AB  - The "concentration clamp" technique has been modified to realize fast and short
      term application of a transmitter to whole neuron followed by its fast washout.
      Prolonged glutamate application evoked activation of the desensitized current.
      The application time was shortened to intervals when the washout corresponded to
      unfinished desensitization of the current. Shortening of the glutamate
      application term to some milliseconds resulted in arising of fast currents which
      maximal amplitude appreciably exceeded that of currents evoked by prolonged
      glutamate application. The role of both components under real synaptic conditions
      is discussed.

PMID- 1359434
TI  - [Physiology of Skin Receptors. Conference. Novgorod, Russia, 21-22 May 1992].

PMID- 1359435
TI  - Abstracts of the Internistendagen. 9-10 April 1992.

PMID- 1359436
TI  - Intoxication with beta-sympathicolytics.
AB  - Based on the review of available literature, this article states the possible
      clinical problems with beta-blocker intoxication. Some 26% of severe cases of
      intoxication will die. This fact stimulated the attempt, using animal
      experiments, to gain an insight into the pathophysiological profile of this
      intoxication. The results of these animal experiments led to the following
      conclusion: toxic doses of beta-blockers result in a dose-dependent decrease of
      myocardial contractility. This negative inotropic effect is not related to the
      antagonizing effects of the beta-blocker at the beta-adrenergic receptor level,
      nor to the additional properties of this group of drugs, but is influenced by a
      combination of other factors. These include (1) a direct negative inotropic
      effect on the myocardium, probably caused by a calcium dependent mechanism; (2) a
      decrease in serum calcium concentration, probably caused by a decreased
      parathormone production; (3) a centrally mediated hypotensive action. Toxic doses
      of beta-blockers do not only affect the myocardium and the haemodynamic system,
      they can also lead to respiratory arrest. This arrest is caused by the direct
      effect of these drugs on the central nervous system and can, in itself, be the
      cause of death. Such results lead to the following therapeutic advice: patients
      with severe beta-blocker intoxication must be admitted to an Intensive Care Unit,
      as early initiation of ventilation, as well as administration of beta-antagonist
      can be essential; the drop in serum calcium concentration must be corrected;
      drugs which can improve myocardial contractility, other than via the beta
      adrenergic receptor, such as phosphodiesterase inhibitors and glucagon, should be
      administered.

PMID- 1359437
TI  - Positive correlation between proopiomelanocortin and tyrosine hydroxylase mRNA
      levels in the mediobasohypothalamus of ovariectomized rats: response to estradiol
      replacement and withdrawal.
AB  - We have investigated putative dopaminergic regulation of opiomelanotropinergic
      activity in the arcuate/periarcuate mediobasohypothalamus (MBH) by assessing the
      changes in MBH tyrosine hydroxylase (TH; rate-limiting enzyme in catecholamine
      synthesis) and proopiomelanocortin (POMC; opiomelanotropin precursor) mRNA levels
      under conditions in which endogenous tuberinfundibular dopaminergic activity
      exhibits marked changes. Adult Sprague-Dawley rats were sacrificed at 09.00 and
      15.00 h, and individual MBH POMC and TH cytoplasmic mRNA levels were
      simultaneously quantified by multiplex solution hybridization-RNase protection
      assay with protected fragments separated by polyacrylamide gel electrophoresis.
      In ovariectomized (OVX) rats treated for 3 days with low-dose estradiol (E2)
      implants (resulting in 18 +/- 4 pg E2/ml serum), the MBH levels of POMC and TH
      mRNAs were approximately 17 and 31% lower than those measured in OVX controls,
      respectively. In OVX rats implanted for 20 days with larger E2 implants (99 +/- 9
      pg E2/ml serum), POMC and TH mRNA levels were approximately 29 and 41% lower than
      in OVX controls, respectively. Additional groups were exposed to the higher E2
      dose for 20 days and then killed 10 or 20 days after removal of the E2 implant.
      In these rats, POMC mRNA levels rebounded to the same level seen in OVX controls,
      while TH mRNA levels even exceeded control values by 22-27%. TH and POMC mRNA
      levels did not change significantly between 09.00 and 15.00 h, except 10 days
      after removal of the E2 implants, when 09.00 h POMC mRNA levels were higher than
      the 15.00 h levels. MBH POMC and TH mRNA levels were positively correlated with
      each other within individual animals. This correlation is maintained when both
      POMC and TH mRNA levels are suppressed in response to both 3-day low-dose and 20
      day high-dose E2 treatment. However, although rat MBH opiomelanotropinergic and
      tuberoinfundibular dopaminergic mRNA biosynthesis thus appear to be positively
      correlated, the coregulation or functional interactions of these two neuronal
      systems remain to be determined.

PMID- 1359438
TI  - Dexmedetomidine, a potent and highly specific alpha 2 agonist, evokes cytosolic
      calcium surge in astrocytes but not in neurons.
AB  - Dexmedetomidine is an extremely potent alpha 2 adrenoceptor agonist which can
      reduce anaesthetic requirements by up to 90%. However, the precise cellular
      mechanism of action of this agent is not known. Primary cultures of murine
      neurons and astrocytes were grown to test the hypothesis that changes in free
      intracellular calcium may trigger cellular responses to this drug. In astrocyte
      cultures, experiments revealed a pronounced increase in cytosolic calcium
      concentration when 100 nM dexmedetomidine was administered. However, in cultured
      cerebellar granule cell neurons there was no calcium response observed with
      similar or even higher concentrations of the drug. Results suggest
      dexmedetomidine may exert its primary effect on the central nervous system via
      astrocytes.

PMID- 1359439
TI  - Neuroendocrine responses to the serotonin2 agonist DOI are differentially
      modified by three 5-HT1A agonists.
AB  - Evidence suggests that activation of 5-HT1A receptors leads to inhibition of 5
      HT2-mediated behavior. The purpose of this study was to investigate the
      interaction between 5-HT1A and 5-HT2 receptor-mediated hormone secretion. Rats
      were pretreated with the 5-HT1A agonists buspirone (0, 0.5, 2.0 mg/kg, i.p.), 8
      OH-DPAT (0, 0.05, 0.2 mg/kg, s.c.) or ipsapirone (0, 1.0, 2.5 mg/kg, i.p.), 45
      min before decapitation. The 5-HT2 agonist DOI was administered (0-10 mg/kg,
      i.p.) 15 min after injection of the 5-HT1A agonists. The three 5-HT1A agonists
      differentially altered the DOI-induced increase of concentrations of hormone in
      plasma. None of the three 5-HT1A agonists influenced the basal levels of renin,
      ACTH and prolactin but 8-OH-DPAT and buspirone increased the basal level of
      corticosterone in plasma. Also, 8-OH-DPAT increased the effects of DOI on the
      concentration of ACTH in plasma but ipsapirone and buspirone did not. None of the
      5-HT1A agonists significantly affected DOI-induced increase of concentration of
      corticosterone in plasma. Buspirone and 8-OH-DPAT potentiated the effect of DOI
      on prolactin in plasma, but ipsapirone did not. Ipsapirone potentiated the effect
      of DOI on the concentration of renin in plasma but this effect was not observed
      in 8-OH-DPAT- and buspirone-pretreated rats. The results do not support the
      hypothesis for a functional interaction between 5-HT1A and 5-HT2 receptors, since
      the three 5-HT1A agonists did not have the same influence on the hormonal effects
      of DOI.

PMID- 1359440
TI  - Effects of intracerebroventricularly administered mu-, delta- and kappa-opioid
      agonists on locomotor activity of the guinea pig and the pharmacology of the
      locomotor response to U50,488H.
AB  - The effects of intracerebroventricular administration of morphine, the selective
      mu-agonist DAMGO, the delta-agonist DPDPE, the kappa-preferring peptide dynorphin
      A(1-13) and the kappa-agonist U50,488H on locomotor behaviour in the guinea pig
      were investigated. Morphine (total dose = 0.01, 0.1, 1, 10, 200 nmol), DAMGO and
      DPDPE (total dose = 0.1, 1, 10, 100 nmol of each) produced piloerection and
      sedation, indicating that the responses of guinea pigs to mu- and delta-opioid
      agonists differed from those of rats and mice. In contrast, U50,488H (total dose
      = 10, 100 nmol) and dynorphin A(1-13) (total dose = 100 nmol) produced increased
      locomotor activity which was attenuated by pretreatment with naloxone and
      norbinaltorphimine, thus confirming the involvement of kappa-opioid receptors.
      Furthermore, pretreatment with spantide, baclofen, muscimol, bicuculline, MK-801,
      raclopride and atropine also inhibited the U50,488H-induced locomotor activity,
      suggesting the involvement of GABA, dopamine, excitatory amino acids, substance P
      and acetylcholine in this response.

PMID- 1359441
TI  - Further studies of the role of opioid receptors in the nigra in the morphine
      withdrawal syndrome.
AB  - Bilateral injection of naloxone (3.0-30.0 nmol) into the substantia nigra of
      morphine-dependent rats produced a withdrawal syndrome consisting of wet-dog
      shakes, teeth chattering, irritability to touch, diarrhea and hypothermia.
      Intense wet-dog shakes and grooming were observed after intranigral injection of
      the mu selective antagonist D-Phe-Cys-Try-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP, 3.0
      30.0 nmol) in morphine-dependent animals. Body temperature after 30.0 nmol CTOP
      was significantly increased. A significant positive correlation between body
      temperature and wet-dog shakes was observed in morphine-dependent animals that
      received CTOP. Intranigral injection of beta-funaltrexamine (beta-FNA, 10.0
      nmol), an irreversible mu antagonist, produced no signs of withdrawal in morphine
      dependent animals. However, intranigral injection of beta-FNA (1.0-3.0 nmol)
      suppressed the antinociceptive effect of the mu-selective agonist, D-Ala2,N-Me
      Phe4,Gly5-ol-enkephalin (DAGO, 1.0 nmol). The withdrawal syndrome produced by
      CTOP (10.0 nmol) was not suppressed by the administration of U50,488H (10.0
      nmol), a kappa agonist, suggesting that the absence of an effect of beta-FNA was
      not due to its kappa agonist activity. Neither the delta-selective antagonist,
      naltrindole (NTI, 10.0 nmol) nor the kappa-selective antagonist, nor
      binaltorphimine (nor-BNI, 10.0 nmol) produced withdrawal. Only wet-dog shakes
      were observed when CTOP, NTI and nor-BNI (5 nmol each) were administered together
      into the nigra. These studies suggest an involvement of mu receptors in the nigra
      in the wet-dog shakes and thermoregulatory dysfunction that occur during
      withdrawal of morphine. However, the subtypes of opioid receptors in the nigra,
      that mediate the other signs of morphine withdrawal remain obscure.

PMID- 1359442
TI  - Systemic administration of dynorphin A(1-13) markedly inhibits different
      behavioural responses induced by cocaine in the mouse.
AB  - The effects of systemic administration (i.p.) of dynorphin A(1-13) on the cocaine
      induced behavioural alterations in the mouse were determined by using multi
      dimensional behavioural analyses, based upon a capacitance system. A 1.0 mg/kg
      dose of cocaine did not influence behaviour, while increasing doses to 3-30 mg/kg
      produced a significant increment in the frequency of behaviour, such as linear
      locomotion, circling, rearing and grooming. Although a 1.0 mg/kg dose of
      dynorphin A(1-13) alone produced a significant decrease in grooming behaviour,
      larger doses (3.0 and 10.0 mg/kg) of the peptide failed to affect different
      behaviour. The cocaine (3.0 mg/kg)-induced increases in linear locomotion,
      circling and rearing behaviour were significantly inhibited by dynorphin A(1-13)
      (10.0 mg/kg). The inhibitory effects of dynorphin A(1-13) (10.0 mg/kg) were
      antagonized by the opioid antagonist Mr 2266 (5.6 mg/kg). It is thus possible
      that the systemic administration of dynorphin A(1-13) inhibits different
      behavioural responses induced by cocaine through the blood-brain barrier,
      although the instability of amino acid bonds or the relatively large molecular
      weight of dynorphin A(1-13), may result in the failure to demonstrate opioid
      activity by the peptide after systemic administration.

PMID- 1359443
TI  - Interactions of endogenous opioid and excitatory amino acid inputs to the caudal
      ventrolateral medulla of the rat.
AB  - This study investigated the cardiovascular consequences of interactions between
      endogenous opioid and excitatory amino acid inputs to the caudal ventrolateral
      medulla of the anaesthetised rat. Drugs were injected bilaterally into the
      functionally identified depressor region of the caudal ventrolateral medulla. The
      opioid antagonist, naloxone (2.5-8.0 nmol/side) elicited a dose-dependent
      decrease in blood pressure and a bradycardia. The NMDA-receptor antagonist, 2
      amino, 5-phosphonovaleric acid (2-APV; 1.25-500 pmol/side), dose-dependently
      increased blood pressure but had little effect on heart rate. After the maximum
      dose of naloxone, the pressor response to both 1.25 and 25 pmol/side of 2-APV was
      attenuated by 89 and 66%, respectively. By contrast, the pressor response,
      elicited by injection of the GABA agonist, muscimol (1 pmol/side), was not
      affected. After 2-APV (500 pmol/side), the depressor response to 2.5 nmol/side of
      naloxone was enhanced by 84%, although this effect was lost when a larger dose of
      naloxone (5 nmol/side) was used. 2-Amino,5-phosphonovaleric acid also potentiated
      the depressor response to a submaximal dose of the GABA antagonist, bicuculline
      (2 pmol/side). The results suggest firstly that, in the caudal ventrolateral
      medulla, excitatory amino acid inputs are functionally less important when tonic
      opioid effects are blocked. This interaction appears to be pharmacologically
      specific. Secondly, tonic inhibitory inputs, whether due to opioids or to GABA,
      are functionally more effective after excitatory amino acid inputs are
      antagonized.

PMID- 1359444
TI  - Repeated administration of MDMA causes transient down-regulation of serotonin 5
      HT2 receptors.
AB  - The present study examined short- and long-term effects of MDMA (3,4-methylene
      dioxymethamphetamine) on serotonin (5-HT2 and 5-HT1c) receptors in the brain of
      the rat. N1-Methyl-2-[125I]lysergic acid diethylamide ([125I]MIL) was used to
      label these receptors in vitro and in vivo. The usefulness of [125I]MIL for in
      vivo detection of changes in 5-HT2 receptors was confirmed in preliminary
      experiments in which rats were treated chronically with mianserin (5 mg/kg, once
      daily for 10 days). Decreases in specific in vivo binding of [125I]MIL, after
      treatment with mianserin were found to be of the same magnitude as those
      determined by others, using in vitro methods. The MDMA (8 doses; 5-20 mg/kg each)
      was administered to rats over a period of 4 days. At various times after
      administration of the last dose of MDMA, the binding of [125I]MIL was measured.
      Acutely, treatment with MDMA (20 mg/kg) reduced specific in vivo binding of
      [125I]MIL in all regions of brain studied. For example, in the frontal cortex,
      specific binding of [125I]MIL was decreased by 80% at 6 hr and by 62% at 24 hr,
      after cessation of treatment with MDMA. Twenty-one days after administration of
      MDMA however, the number of binding sites for [125I]MIL was back to control
      levels. Reductions in in vivo binding of [125I]MIL in frontal cortex were
      dependent on the dose of MDMA injected and were associated with decreases in the
      number of binding sites for [125I]MIL (Bmax values) in tissue homogenates of the
      same area. Autoradiographic studies of MDMA-treated rats confirmed the decreased
      density of 5-HT2 receptors and also suggested that the 5-HT1c receptor of the
      choroid plexus was not affected. These results indicate that repeated
      administration of MDMA caused transient down-regulation of 5-HT2 receptors in the
      brain of the rat. Further, they demonstrated that [125I]MIL is a suitable
      radioligand for labeling 5-HT2 receptors, both in vitro and in vivo. Once labeled
      with an appropriate radionuclide for SPECT (single photon emission computed
      tomography) or PET (positron emission tomography), MIL should prove useful for
      monitoring changes in the density of serotonin receptors in the living mammalian
      brain.

PMID- 1359445
TI  - The effects of electroconvulsive shock or imipramine on subtypes of alpha 1
      adrenoceptors in the frontal cortex of the rat.
AB  - The effects of repeated treatment (14 days) with electroconvulsive shock (ECS) or
      imipramine on binding sites on alpha 1-adrenoceptors in the rat were studied. The
      binding of [3H]prazosin studied with WB4101 and phentolamine, as binding
      inhibitors, showed the existence of two subtypes of alpha 1-adrenoceptor (alpha
      1A and alpha 1B). Proportions of the alpha 1A and alpha 1B binding sites were
      about 3:7 in the frontal cortex and 9:1 in the hippocampus. Pretreatment of the
      membranes with chlorethylclonidine (CEC) almost abolished the alpha 1B binding
      sites. Inhibition of the binding of [3H]prazosin studied with antidepressants
      (imipramine, desipramine, maprotiline and mianserin) showed that these drugs
      bound to alpha 1-adrenoceptors with low affinity, in an apparent monophasic
      manner. The characteristics of the alpha 1A and alpha 1B binding sites were
      studied by the binding assay with [3H]prazosin, in the presence of a small
      concentration (2 nM) of WB4101 to mask the alpha 1A binding sites, as well as the
      assay without WB4101, for the total alpha 1-adrenoceptor (alpha 1A and alpha 1B)
      binding. Repeated treatment with electroconvulsive shock increased but that with
      imipramine decreased, the density of the alpha 1B binding sites in the frontal
      cortex, without change of the affinity. Neither treatment affected the alpha 1A
      binding sites in the frontal cortex. The alpha 1-adrenoceptors (alpha 1A and
      alpha 1B) in the hippocampus were not affected at all by these repeated
      treatments. The electroconvulsive shock-induced increase in the alpha 1B binding
      sites in the frontal cortex of the rat could contribute to differences in
      clinical effects between electroconvulsive shock and antidepressant drugs.

PMID- 1359446
TI  - Lack of involvement of haloperidol-sensitive sigma binding sites in modulation of
      dopamine neuronal activity and induction of dystonias by antipsychotic drugs.
AB  - The present studies evaluated previous suggestions that haloperidol-sensitive
      sigma binding sites are involved in the modulation of dopamine (DA) neuronal
      activity and in the induction of the dystonic effects of antipsychotic drugs.
      These issues were addressed by evaluating the effects of compounds that have
      differing affinities for sigma binding sites, on the firing activity of DA
      neurons in the substantia nigra in chloral hydrate-anesthetized rats and on the
      ability to induce extrapyramidal motor dysfunction in squirrel monkeys sensitized
      to the dystonic effects of haloperidol. The agents studied included haloperidol,
      DTG (1,3-di-o-tolylguanidine), (+)-pentazocine, (+)-SKF 10,047, BMY 14802, 8-OH
      DPAT and sulpiride. There was no relationship between affinity for sigma binding
      sites and the ability to either alter DA neuronal activity or to induce
      extrapyramidal motor dysfunction.

PMID- 1359447
TI  - Differential modulation of Purkinje cell activity by enkephalin and corticotropin
      releasing factor.
AB  - Several peptides have been localized within afferents to the opossum's
      cerebellum, including cholecystokinin (15), enkephalin (16, 17) and corticotropin
      releasing factor (7, 9). Each of these peptides has a heterogeneous laminar and
      lobular distribution. Two peptide, enkephalin (ENK) and corticotropin releasing
      factor (CRF) are present in specific populations of climbing fibers and mossy
      fibers, which have an overlapping distribution in several areas of the
      cerebellum, in particular the lateral aspect of vermal lobules VII and VIII.
      Within this location ENK and CRF are co-localized in individual climbing fibers
      and mossy fibers (7). In the present study, the physiological effects of these
      peptides on Purkinje cell activity were analyzed. The data indicate that ENK and
      CRF have opposite effects on Purkinje cell activity. ENK suppresses spontaneous
      activity as well as that induced by application of glutamate and aspartate, as
      described previously (5). In contrast, CRF enhances both spontaneous and amino
      acid-induced unit activity. Further, when applied simultaneously, CRF blocks the
      suppressive effect induced by ENK. Previous studies have shown that climbing
      fibers, as well as the mossy fiber-parallel fiber pathway, are excitatory to
      Purkinje cells (11). However, immunohistochemical data have shown that these
      afferents are heterogeneous with respect to their chemical content (7-9, 15-17,
      25). As found in the current and previous studies (3, 5) peptides in climbing and
      mossy fibers modulate the responsiveness of Purkinje cells to primary excitatory
      neurotransmitters in selected areas of the cerebellar cortex. However, the firing
      rate of individual Purkinje cells is differentially altered depending on which
      neurochemical messenger(s) are released.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359448
TI  - Role of dopamine receptors in the regulation of aggression in mice; relationship
      to genotype.
AB  - The interline differences in the manifestation of aggression evoked by
      stimulation was studied in mice of eight inbred lines, and the role of different
      types of dopamine (DA) receptors in its manifestation was investigated.
      Aggression was assessed in a test involving the effect of a weak electrical
      stimulation through the floor of the cage. A significant relationship to the
      animals' genotype was demonstrated, and low-aggression (C3h/He, DD, BALB/c, and
      AKR) and high-aggression (CBA, DBA/2, and CC57Br) lines could be distinguished on
      the basis of the level of aggressivity. The mixed agonist of DA receptors,
      apomorphine, in a one-time administration activated aggressivity in the low
      aggression mice. The selective stimulation of D2-receptors with bromocriptine
      substantially increased the evoked aggressivity in the low-aggression mice; the
      blockade of D2-receptors by sulpiride decreased or prevented the manifestation of
      aggressivity in the high-aggression lines. At the same time, the selective D1
      agonist SKF 38393 and the selective D1-antagonist SCH 23390 did not exert a
      substantial influence on evoked aggressivity. Evidently the D2-receptors play a
      key role in the control of aggression evoked by stimulation, which constitutes a
      model of affective aggression.

PMID- 1359449
TI  - Contrast-enhanced magnetic resonance imaging of sub- and epidural empyemas.
AB  - Contrast-enhanced magnetic resonance images (MRI) of three patients with subdural
      (SDE) and two with epidural empyemas (EDE) were reviewed. In each case, the
      capsule of the lesion demonstrated enhancement, and distinction between capsule
      and contents was obvious on contrast-enhanced images. In SDE, contrast-enhanced
      images clearly depicted thickening of the neighbouring dura mater and a co
      existent brain abscess. In EDE, part of the displaced dura mater did not enhance,
      which facilitated differentiation from SDE. Contrast-enhanced MRI was thus of
      value in diagnosis.

PMID- 1359450
TI  - Analysis of synaptic events in the mouse accessory olfactory bulb with current
      source-density techniques.
AB  - The accessory olfactory bulb of the mouse was studied by current source-density
      analysis of field potentials to determine the laminar and temporal distribution
      of synaptic currents evoked by electrical stimulation of the vomeronasal organ.
      The one-dimensional current source-density analysis revealed two major spatially
      and temporally distinct inward membrane currents (sinks): one in the glomerular
      layer and the other in the external plexiform layer. The glomerular layer sink
      preceded the external plexiform layer sink by a mean of 5.5 ms. Local infusions
      of the broad-spectrum excitatory amino acid antagonist, kynurenate, into the
      accessory olfactory bulb blocked the external plexiform layer sink without an
      obvious effect on the glomerular layer sink. The selective non-N-methyl-D
      aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione produced a
      dose-dependent blockade of the external plexiform layer sink, whereas the
      selective N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovalerate
      was without effect. These results, taken together with the cytoarchitecture of
      the accessory olfactory bulb, suggest that the glomerular layer sink results
      mainly from synaptic excitation evoked in the glomerular dendritic branches of
      mitral cells by the vomeronasal afferent fibres and the external plexiform layer
      sink mainly from non-N-methyl-D-aspartate receptor-mediated synaptic excitation
      in the peripheral processes of granule cells via the mitral to granule cell
      dendrodendritic synapse.

PMID- 1359451
TI  - D1 and D2 dopamine receptors differentially regulate c-fos expression in
      striatonigral and striatopallidal neurons.
AB  - The expression of Fos, the product of the proto-oncogene c-fos, is thought to be
      a marker of neuronal activity. D1, but not D2, dopamine receptor agonists have
      previously been shown to increase Fos immunoreactivity in striatonigral neurons
      ipsilateral to a 6-hydroxydopamine lesion of the nigrostriatal pathway. In the
      present study, it was demonstrated that the D1 receptor agonist SKF 38393 rarely
      increased Fos in striatopallidal neurons of the 6-hydroxydopamine denervated
      striatum. Conversely, in the intact striatum, the D2 receptor antagonist
      haloperidol enhanced Fos expression predominantly in striatopallidal neurons
      labelled retrogradely from the globus pallidus or with an oligonucleotide probe
      complementary to mRNA encoding enkephalin. These results are consistent with
      studies suggesting that D1 receptors are located predominantly on striatonigral
      neurons and that D2 receptors reside principally on enkephalin-containing
      striatopallidal neurons. They also provide a neuroanatomical basis for
      neurochemical and neurophysiological observations indicating that dopamine
      facilitates the activity of striatonigral neurons but inhibits striatopallidal
      neurons. In another experiment the selective D2 receptor agonist quinpirole was
      found to increase Fos immunoreactivity in the globus pallidus ipsilateral to a 6
      hydroxydopamine lesion. It is proposed that this may have been due to a D2
      receptor-mediated inhibition of enkephalin and GABA release from striatopallidal
      terminals that in turn disinhibited the pallidal neurons. In a final series of
      experiments, brain microdialysis was used to determine the location of dopamine
      receptors regulating striatal Fos expression. Local application of the selective
      D1 receptor agonist CY 208-243 in the 6-hydroxydopamine-denervated striatum, or
      of haloperidol in the intact striatum via the dialysis probe increased Fos
      immunoreactivity in the immediate vicinity of the probe. Hence, the inductive
      effects of these systematically administered compounds on Fos expression in the
      striatum are mediated at least partly by local dopamine receptors in the
      striatum. Taken together, these results suggest that the differential regulation
      of striatonigral and striatopallidal activity by dopamine is mediated by the
      largely separate location of D1 and D2 receptors on these outputs.

PMID- 1359452
TI  - Acute and repeated administration of fluphenazine-N-mustard alters levels of
      tyrosine hydroxylase mRNA in subsets of mesencephalic dopaminergic neurons.
AB  - Changes in striatal dopamine turnover and levels of tyrosine hydroxylase
      messenger RNA were examined in mice injected with D2 selective doses of
      fluphenazine-N-mustard, an irreversible blocker of dopaminergic receptors. The
      animals were killed at different times after acute and repeated injections of the
      drug and dopamine turnover was assessed by measuring dopamine and its metabolite,
      dihydroxyphenylalanine, in the striatum. Tyrosine hydroxylase mRNA was measured
      at the single-cell level in neurons of the substantia nigra pars compacta and the
      ventral tegmental area with quantitative in situ hybridization histochemistry.
      Acute treatment with fluphenazine-N-mustard induced an increase in both striatal
      dopamine turnover and the level of tyrosine hydroxylase mRNA in the substantia
      nigra but not the ventral tegmental area. After two days of repeated drug
      injections (twice daily), tyrosine hydroxylase mRNA was decreased in the
      substantia nigra despite the persistence of an elevated dopamine turnover in the
      striatum. The decrease in mRNA was still observed after four days of repeated
      treatment while, at that time, turnover values were not different from control.
      No changes were observed in the ventral tegmental area. The initial increase in
      tyrosine hydroxylase mRNA in substantia nigra pars compacta suggests that
      activation of nigrostriatal neurons triggers a very rapid increase in genomic
      expression of the enzyme. The following decrease in mRNA levels precedes
      desensitization to the effects of the drug on dopamine turnover, further
      illustrating a lack of correspondence between increased neurotransmission and
      levels of tyrosine hydroxylase mRNA in catecholaminergic neurons of the central
      nervous system.

PMID- 1359453
TI  - A neuroleptic-like effect of ceronapril on latent inhibition.
AB  - Three experiments that used a latent inhibition procedure to investigate the
      effects of ceronapril on attentional processes in the rat are reported. Latent
      inhibition is a behavioural paradigm in which prior exposure to a stimulus with
      no significant consequences retards subsequent conditioning to that stimulus when
      it is paired with reinforcement. Latent inhibition reflects a process of learning
      to ignore, or tune out, irrelevant stimuli, and has been suggested as an animal
      model of the attentional processes disrupted in the acute phase of schizophrenia.
      In animals, latent inhibition is disrupted by the administration of low doses of
      amphetamine and enhanced by the administration of neuroleptics. Ceronapril is an
      angiotensin converting enzyme inhibitor that has been shown to retard the
      breakdown of central cholecystokinin. It has been proposed that elevation of
      cholecystokinin levels in the brain may possess neuroleptic-like properties. We
      assessed this possibility by determining the effects of ceronapril on latent
      inhibition using a conditioned emotional response procedure, consisting of three
      stages: pre-exposure, in which the to-be-conditioned stimulus, a tone, was
      repeatedly presented without reinforcement; conditioning, in which the pre
      exposed stimulus was paired with shock; and test, where latent inhibition was
      indexed by animals' suppression of licking during tone presentation. In
      Experiment 1, 20 tone pre-exposures were given, and conditioning consisted of
      five tone-shock pairings; we assessed the effects of 0.005 mg/kg, 0.05 mg/kg and
      0.5 mg/kg ceronapril, compared with vehicle injections. In Experiment 2, five
      tone pre-exposures were given, and conditioning consisted of two tone-shock
      pairings: we assessed the effects of 0.05 mg/kg ceronapril, compared with vehicle
      injections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359454
TI  - Dissociated high-purity dopaminergic neuron cultures from the substantia nigra
      and the ventral tegmental area of the postnatal rat.
AB  - We have developed dissociated primary neuronal cultures obtained from the
      substantia nigra and from the ventral tegmental area of postnatal rats (two to
      three days old). After making brain slices, the regions of the substantia nigra
      and the ventral tegmental area were separately dissected. The removed fragments
      of brain tissue were dissociated and cultured on a glial feeder layer. Double
      immunocytochemical labeling for tyrosine hydroxylase and GABA on cultures grown
      for two to three weeks showed the presence of 42% dopaminergic and 39% GABAergic
      neurons in substantia nigra cultures, whereas in ventral tegmental area cultures
      there were 65% dopaminergic and 21% GABAergic neurons. The dopaminergic neurons
      were characterized by thick and straight primary processes dividing into several
      branches. Varicosities were found mainly on distal parts of the processes. In
      contrast, GABAergic neurons possessed highly branched thick and thin primary
      processes with intensive arborization and numerous varicosities. Co-existence of
      dopamine and cholecystokinin was found in about 70% of dopaminergic neurons from
      the substantia nigra and in about 35% of dopaminergic neurons from the ventral
      tegmental area. Physiological properties of these cultured dopaminergic neurons
      were investigated with the whole-cell version of the patch-clamp method. After
      each physiological experiment, immunocytochemical labeling confirmed that the
      cell was dopaminergic. Properties of single action potentials, with an action
      potential height of 92 mV and duration of 1.6 ms, were similar to those reported
      for dopaminergic neurons in brain slices. The neurons showed a high resting
      potential, and no spontaneous firing of action potentials. Constant current
      depolarizations elicited trains of action potentials. In the majority of cells,
      the train stopped firing within a few seconds, while in some cells it lasted
      indefinitely. When the cell was hyperpolarized, the voltage response started to
      decline slowly (sag), indicating the presence of hyperpolarization-activated
      currents (time-dependent inward rectification). These results show that by using
      our culture method it is possible to obtain separate dissociated cultures of the
      substantia nigra and the ventral tegmental area from newborn rats. Because they
      are rich in functional dopaminergic neurons, these cultures will be a useful tool
      for studying various properties of dopaminergic neurons.

PMID- 1359455
TI  - Pentylenetetrazol kindling and factors of glutamate transmitter metabolism in rat
      hippocampus.
AB  - Male Wistar rats administered repetitively with pentylenetetrazol developed a
      dose-dependent enhancement of seizure behaviour referred to as pentylenetetrazol
      kindling. After a daily dose of 40 mg pentylenetetrazol/kg or physiological
      saline (control rats) injected intraperitoneally for a period of two weeks,
      hippocampal tissue was studied autoradiographically for high-affinity uptake of
      [3H]glutamate and, by activity staining, for aspartate aminotransferase and
      glutamate dehydrogenase. Most prominent changes were found in neuropil areas
      known to be endowed with glutamatergic structures. The uptake capacity of
      glutamate decreased by 48% (maximum rate), whilst activities of aspartate
      aminotransferase and glutamate dehydrogenase elevated to 140 and 130%,
      respectively. Cytochrome c oxidase activity was found to be unaffected. The
      findings indicate an important role of factors of the glutamate metabolism in the
      kindling process with respect to the production, utilization, and availability of
      transmitter glutamate.

PMID- 1359456
TI  - Inhibition of nigral dopamine neurons by systemic and local apomorphine: possible
      contribution of dendritic autoreceptors.
AB  - Peripheral administration of low doses of dopamine agonist apomorphine induces a
      strong and short-latency inhibition of dopamine neurons in the substantia nigra,
      presumably via the activation of somatodendritic autoreceptors. We studied the
      site of action of apomorphine in anesthetized rats using volume-controlled
      pressure microejection combined with single unit recordings. Microapplication of
      apomorphine in the immediate vicinity of nigral dopamine neurons did not mimic
      the effect of intravenous administration of apomorphine (50 micrograms/kg),
      regardless of the concentration or volume used (10(-10)-10(-2) M, 10-100 nl). In
      contrast, the inhibition produced by systemic apomorphine was mimicked by drug
      application at a site 300 microns lateral and 600 microns ventral from the
      recording site in the zona reticulata of the substantia nigra, a region rich in
      dendrites of dopamine neurons. The inhibition induced by such a distant
      application of apomorphine could be reversed by systemic injection of D2, but not
      D1, receptor antagonists. Non-dopaminergic substances such as GABA, bicuculline
      or lidocaine were more effective when ejected close to rather than distant from
      the recording site, in a manner opposite to that of apomorphine. Similar to
      apomorphine, dopamine and D2 receptor agonists were more potent when intranigral
      applications were made at sites distant from, rather than close to, the recorded
      dopamine cells. Ejection of D2 antagonists in the substantia nigra zona
      reticulata attenuated the inhibitory effect of subsequent systemic apomorphine.
      Our results, together with other previous studies on the location of D2 receptors
      on dopamine neurons, suggest that peripheral administration of low doses of
      apomorphine inhibits nigral dopamine neurons by acting at D2 receptors located on
      the dendrites of these neurons.

PMID- 1359457
TI  - Excitatory synaptic potentials in neurons of the deep nuclei in olivo-cerebellar
      slice cultures.
AB  - Excitatory postsynaptic potentials evoked in neurons of the deep cerebellar
      nuclei, either by electrical stimulation within the nuclei in cerebellar slice
      cultures or by electrical stimulation of olivary explants in olivo-cerebellar co
      cultures, were investigated in the rat by means of intracellular recordings. In
      neurons of the deep cerebellar nuclei, stimulation of the nuclear tissue, as well
      as stimulation of the olivary tissue, induced a fast rising excitatory
      postsynaptic potential, followed by an inhibitory postsynaptic potential and a
      long-lasting excitation. The fast rising excitatory postsynaptic potential and
      the following inhibitory postsynaptic potential were blocked by 6-cyano-7
      nitroquinoxaline-2,3-dione. The remaining depolarization was abolished by D-(-)-2
      amino-5-phosphonovalerate, suggesting that this potential was mediated by N
      methyl-D-aspartate receptors. With only D-(-)-2-amino-5-phosphonovalerate added
      to the bath, the slow excitation was depressed, whereas the fast excitatory and
      inhibitory postsynaptic potentials were not affected. In the presence of
      bicuculline, the 6-cyano-7-nitroquinoxaline-2,3-dione- and the D-(-)-2-amino-5
      phosphonovalerate-sensitive excitatory postsynaptic potentials elicited by
      stimulation of the olivary tissue had the same latency, and were both graded with
      stimulation strength. The time-to-peak and the duration of the D-(-)-2-amino-5
      phosphonovalerate-sensitive excitatory postsynaptic potentials were considerably
      longer than those of the 6-cyano-7-nitroquinoxaline-2,3-dione-sensitive
      excitatory postsynaptic potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359458
TI  - Cocaine induced synchronous oscillations in central noradrenergic neurons in
      vitro.
AB  - Through inhibition of reuptake, cocaine increases monoaminergic tone in the
      central nervous system. The activities of the neurons within the locus coeruleus
      play a pivotal role in central noradrenergic transmission and regulate overall
      levels of arousal and attention. We have found that cocaine in low concentrations
      (0.3-1.0 microM) induced slow oscillations (0.8 Hz) in membrane potential (2-6
      mV). These oscillations were synchronized in neurons throughout the nucleus and
      were blocked by alpha 2-adrenergic receptor antagonists. The synchrony of these
      events was thought to arise from within the nucleus, through a combination of
      spontaneous activity (intrinsic properties) and noradrenergic mediated inhibitory
      postsynaptic potentials augmented by cocaine. The synchronous firing of
      noradrenergic neurons may facilitate transmitter release in the widespread
      projection areas and thus be important for the action of cocaine to increase
      levels of arousal.

PMID- 1359459
TI  - Localization of oestrogen receptors in preoptic neurons containing neurotensin
      but not tyrosine hydroxylase, cholecystokinin or luteinizing hormone-releasing
      hormone in the male and female rat.
AB  - The neurochemical identity of preoptic neurons containing oestrogen receptors was
      investigated in the male and female rat using a sequential double-staining
      immunocytochemistry procedure. Single-immunostaining revealed large populations
      of cells with nuclear immunoreactivity to the oestrogen receptor in the medial
      preoptic area of the male and female rat. Optimal double-staining of sections for
      the oestrogen receptor and one of several neuropeptides or tyrosine hydroxylase,
      was achieved with short-term (two- to four-day) gonadectomized rats treated with
      colchicine where necessary. Neurotensin-immunoreactive cells were distributed in
      a sexually dimorphic manner in the region of the anteroventral preoptic nucleus
      and exhibited oestrogen receptor immunoreactivity in both sexes. Double-labelled
      cells in this area of the female rat comprised 50% and 11% of the total
      neurotensin- and oestrogen receptor-containing cell populations, respectively,
      compared with 25% and 4% in the male (P less than 0.01). The numbers of
      neurotensin-immunoreactive cells in the region of the medial preoptic nucleus
      were similar in male and female rats with double-labelled cells making up 20-38%
      and 3-5% of the total numbers of cells containing neurotensin and oestrogen
      receptors, respectively, in both sexes. Neurons immunoreactive for tyrosine
      hydroxylase were distributed in a gender-specific manner within the anterior
      periventricular area but were not immunoreactive for the oestrogen receptor in
      either sex. Following colchicine treatment, cholecystokinin-immunoreactive cells
      were identified predominantly within periventricular regions of the preoptic area
      and similarly, did not possess immunoreactivity to the oestrogen receptor in
      either the male or the female rat. Neurons containing luteinizing hormone
      releasing hormone were found immediately lateral to the cell populations
      containing oestrogen receptors and immunoreactivity to the oestrogen receptor was
      not identified within any neurons containing luteinizing hormone-releasing
      hormone in either the male or female rat. The absence of oestrogen receptor
      immunoreactivity in neurons containing tyrosine hydroxylase, cholecystokinin or
      luteinizing hormone-releasing hormone suggests that gonadal steroids acting
      through this receptor do not influence these cells directly in either sex. In
      particular, it appears that gender-specific patterns of luteinizing hormone
      secretion cannot be attributed to sex differences in oestrogen receptor
      localization within luteinizing hormone-releasing hormone neurons. These
      experiments also show that the sexually dimorphic neurotensin neurons in the
      preoptic area possess oestrogen receptors and that female rats have larger number
      of neurons co-localizing neurotensin and oestrogen receptors. As such, these
      neurons may be involved in mediating sex-specific actions of the gonadal steroids
      in the preoptic area.

PMID- 1359460
TI  - Pressure reversed extracellular striatal dopamine decrease produced by D1
      receptor agonist SKF 38393, and D2 receptor agonist LY 171555, but failed to
      change the effect of the activation of both D1 and D2 receptors.
AB  - When human divers or experimental animals are exposed to high pressure, they
      develop the high-pressure neurological syndrome which is characterized by
      electroencephalographic changes, and behavioral disturbances. Recently,
      neurochemical disorders such as a pressure-induced increase in dopamine release
      have been demonstrated. In the present study, pharmacological experiments, using
      dopamine receptor agonists such as D1 receptor agonist SKF 38393, D2 receptor
      agonist LY 171555, and D1/D2 receptor agonist apomorphine, were performed to
      investigate dopamine receptor function at the neurochemical level. Only
      apomorphine and mixed SKF 38393 + LY 171555 prevented the pressure-induced
      increase in dopamine release while SKF 38393 or LY 171555 administered alone
      failed to do so. The results suggest that the D1-D2 link would be reduced under
      high pressure because of an abnormal function of D1 receptors which would allow
      high-affinity D2 states for dopamine. If so, such a preponderance of high
      affinity states in D2 postsynaptic receptors could be associated with hyperbaric
      hyperlocomotor activity. Elsewhere, results also suggested that the pressure
      induced disorders in dopamine receptor function could be involved in the pressure
      induced elevation in dopamine release.

PMID- 1359461
TI  - Neonatal hypoxic-ischemic or excitotoxic striatal injury results in a decreased
      adult number of substantia nigra neurons.
AB  - It has been shown that morphologic and biochemical presynaptic markers of
      dopaminergic terminals are preserved in a unilateral experimental model of
      neonatal hypoxic-ischemic injury to the striatum. As the substantia nigra is
      spared direct injury in this model, we anticipated that the number of tyrosine
      hydroxylase-positive dopaminergic neurons projecting to the striatum would also
      be normal. We have found, however, that following unilateral neonatal striatal
      injury the number of ipsilateral tyrosine hydroxylase-positive neurons is
      decreased, as is the mean area of the substantia nigra pars compacta. The
      decrease in neurons is correlated with the decrease in striatal size (r = 0.7, P
      = 0.01). Neuron loss is most pronounced in the substantia nigra pars reticulata,
      where it is 50%. Calbindin-positive neurons in the dorsal tier of the substantia
      nigra pars compacta appear to be preserved. We also examined effects on the nigra
      following a neonatal excitotoxic striatal lesion made with quinolinic acid. We
      observed a decrease in the number of substantia nigra tyrosine hydroxylase
      positive neurons in the absence of direct nigral injury, and the decrease was
      closely correlated with reductions in striatal area (r = 0.91, p < 0.01). While
      there are a number of possible explanations for these observations, one major
      possibility is that there has been a reduction in tyrosine hydroxylase-positive
      neurons due to a diminution in developmental target-derived trophic support from
      the striatum. If striatum-derived trophic support plays a role in the
      developmental regulation of substantia nigra neuron number, then abnormalities in
      this supportive relationship may play a role in the loss of these neurons in some
      animal models of developmental nigral degeneration, and some forms of human
      parkinsonism.

PMID- 1359462
TI  - Functional heterogeneity of the matrix compartment in the cat caudate nucleus as
      demonstrated by the cholinergic presynaptic regulation of dopamine release.
AB  - Previously, using a new in vitro microsuperfusion procedure, we have demonstrated
      marked differences in the cholinergic presynaptic regulation of the release of
      [3H]dopamine continuously synthesized from [3H]tyrosine in two close striosomal-
      and matrix-enriched areas of the cat caudate nucleus. A tetrodotoxin-resistant
      stimulatory effect of acetylcholine mediated by muscarinic receptors was observed
      in both compartments. However, in addition, two opposing types of tetrodotoxin
      sensitive acetylcholine-evoked regulation of [3H]dopamine release were only seen
      in the matrix: one facilitatory, involving nicotinic receptors located on as yet
      unidentified neurons, and the other inhibitory, mediated by muscarinic receptors
      located on dynorphin-containing neurons. In the present study, using the same
      approach, a functional heterogeneity was demonstrated in the matrix. Indeed, in
      various conditions the effects of acetylcholine (50 microM) on the release of
      [3H]dopamine were different in a matrix-enriched area (matrix 2) distinct from
      that previously investigated (matrix 1); these areas being characterized by the
      presence or absence of islands of striatonigral cells, respectively. As in matrix
      1, acetylcholine induced a short-lasting stimulation of [3H]dopamine release in
      matrix 2 but, in contrast to that observed in matrix 1, the acetylcholine-evoked
      response in matrix 2 was not modified in the presence of tetrodotoxin (1 microM).
      Experiments made in the presence of the tetrodotoxin and atropine (1 microM)
      indicated that both muscarinic and nicotinic receptors are located on
      dopaminergic nerve terminals in matrix 2 while muscarinic receptors are only
      present in matrix 1. In the absence of tetrodotoxin, the short-lasting
      stimulation of [3H]dopamine release was transformed into a long-lasting response
      in the presence of pempidine (50 microM), in matrix 2 but not in matrix 1 while
      prolonged responses were seen in both matrix areas in the presence of atropine.
      Finally, the acetylcholine short stimulatory effect on [3H]dopamine release was
      transformed into a long stimulatory response in the presence of bicuculline (50
      microM) but not naloxone (1 microM) in matrix 2 while the reverse was observed in
      matrix 1. By providing further evidence for a functional heterogeneity of the
      matrix, our results suggest that depending on the matrix area investigated,
      dynorphin- or GABA-containing neurons are involved in the indirect cholinergic
      inhibitory control of dopamine release.

PMID- 1359464
TI  - [The use of somatostatin in the therapy of acute pancreatitis].
AB  - The authors report their experience in the use of somatostatin in severe acute
      pancreatitis. From 1985 to 1990, 169 patients with severe acute pancreatitis have
      been observed in the Surgery Division of "S. Andrea" Hospital in Vercelli. After
      the introduction, the evaluation of methods employed and results obtained, the
      authors conclude that somatostatin can give a good response in this kind of
      patient without side effects or complications.

PMID- 1359463
TI  - Distributions of neuropeptide Y, vasoactive intestinal peptide and somatostatin
      in populations of postganglionic neurons innervating the rat kidney, spleen and
      intestine.
AB  - Some peripheral peptidergic nerves selectively innervate different types of
      tissue in abdominal organs. Neuropeptide Y- and vasoactive intestinal peptide
      immunoreactive nerve terminals have been identified in the kidney, spleen and
      intestine and these peptides may have important physiological actions.
      Somatostatin has been found in sympathetic ganglia, and nerve terminals
      containing this peptide have been identified in the intestine. We have used
      fluorescent retrograde tracers to identify renal, splenic and mesenteric
      postganglionic neurons in rat sympathetic ganglia and then used
      immunocytochemistry to determine the proportions of these three identified groups
      of neurons displaying immunoreactivity for neuropeptide Y, vasoactive intestinal
      peptide and somatostatin. Most renal, splenic and mesenteric neurons were
      immunoreactive for neuropeptide Y and less than 1% of cells innervating these
      organs were immunoreactive for vasoactive intestinal peptide. Somatostatin
      immunoreactivity was present only in a small percentage of mesenteric neurons and
      not in renal or splenic neurons. The present study demonstrates that (i) the rat
      kidney, spleen and intestine do not differ in the proportion of innervation by
      neuropeptide Y-immunoreactive neurons, (ii) the solar plexus, splanchnic ganglion
      and chain ganglia (T12 and T13) provide very little vasoactive intestinal peptide
      immunoreactive inputs to these organs, and (iii) somatostatin-immunoreactive
      neurons innervate the intestine but not the kidney or spleen.

PMID- 1359465
TI  - [The efficacy of the omeprazole-levosulpiride combination in the therapy of
      distal reflux esophagitis].
AB  - The therapeutic effectiveness of levosulpiride associated with omeprazole versus
      omeprazole alone in the reflux esophagitis has been evaluated. Two groups, each
      of 9 patients, were investigated before and after therapy on a clinical ground
      and endoscopically. While no difference was shown in terms of macro and
      microscopic resolution, a better subjective relief was obtained in the group
      treated with the association levosulpiride-omeprazole.

PMID- 1359466
TI  - Differing effects of alpha-difluoromethylornithine and CGP 40116 on polyamine
      levels and infarct volume in a rat model of focal cerebral ischaemia.
AB  - Focal cerebral ischaemia was induced in rats by occlusion of the left middle
      cerebral artery. Two days later, infarct volume was determined by magnetic
      resonance imaging and the concentrations of the polyamines putrescine (PU),
      spermine and spermidine by HPLC. In control (occluded) animals, PU levels were
      elevated in infarcted and non-infarcted areas of the left hemisphere. Treatment
      with the ornithine decarboxylase (ODC) inhibitor alpha-difluoromethylornithine,
      prevented the ischaemia-induced increase in tissue PU without affecting infarct
      volume. Conversely, administration of the N-methyl-D-aspartate (NMDA) receptor
      antagonist CGP 40116 decreased cortical infarction without changing the tissue
      content of PU. We conclude that there is no direct link between NMDA receptor
      activation and brain PU, or PU and post-ischaemic tissue damage, and that
      inhibitors of ODC are not cerebroprotective in this animal model of stroke.

PMID- 1359467
TI  - Glutamate-induced ribosomal disaggregation and ultrastructural changes in rat
      cortical neuronal culture: protective effect of horse serum.
AB  - Differentiated primary cortical neuronal cultures of rat were exposed for 5 min
      to 0.1 and 1.0 mM glutamate. In cultures maintained in serum-free medium after
      glutamate exposure, ribosomes completely disaggregated and neurons died within 24
      h already after 0.1 mM glutamate. Addition of 5% horse serum to the culture
      medium prevented both ribosomal disaggregation and neuronal death even after
      exposure to 1.0 mM glutamate. Glutamate toxicity in vitro requires removal of
      serum-associated growth factors from the incubation medium and, therefore, may
      not be representative for neuronal vulnerability in vivo.

PMID- 1359468
TI  - Lesions of nigrostriatal pathway reduce expression of tyrosine hydroxylase gene
      in residual dopaminergic neurons of substantia nigra.
AB  - The effects of unilateral mechanical transection of the nigrostriatal bundle of
      rat brain on the level of tyrosine hydroxylase (TH) mRNA and on the activity of
      TH enzyme in the substantia nigra (SN) were examined. Lesions resulted, by 14
      days, in reductions of TH mRNA level to 10% of control and of TH enzyme activity
      to 39% of control in the ipsilateral SN. The percentage of TH mRNA is lower than
      either the percentage of surviving dopaminergic neurons or the remaining TH
      enzyme activity. In situ hybridization analyses also demonstrated the reduction
      of TH mRNA concentration in surviving dopaminergic neurons in the ipsilateral SN.

PMID- 1359469
TI  - Elicitation of penile erection following activation of the hippocampal formation
      in the rat.
AB  - We explore the possible involvement of the hippocampal formation in penile
      erection, using male, adult Sprague-Dawley rats that were anesthetized with
      pentobarbital sodium. The intracavernous pressure (ICP) was used as the
      experimental index for penile erection. Electrical activation of the hippocampal
      formation resulted in two patterns, viz, multiple and single episodes of
      elevation in ICP, along with visible penile erection and ejaculation. The former
      pattern exhibited an increase in ICP that was more sustained, with higher peak
      amplitude and longer latency. Furthermore, they originated respectively from the
      granule cells of the dentate gyrus and pyramidal cells of the CA1 and CA3 fields
      of the Ammon's horn. Chemical stimulation of the hippocampus with glutamate also
      elicited significant increase in ICP. These results thus provided direct evidence
      to establish that the hippocampal formation may be involved in central neural
      regulation of the erectile process.

PMID- 1359470
TI  - Apamin reduces the late afterhyperpolarization of lamprey spinal neurons, with
      little effect on fictive swimming.
AB  - The role of the late afterhyperpolarization (late AHP) in the firing properties
      of lamprey spinal neurons was tested by bath application of apamin, a selective
      blocker of the sk calcium-dependent potassium current. Intracellular recordings
      of identified motoneurons and interneurons were made with micropipette electrodes
      in the isolated lamprey spinal cord. Apamin reversibly reduced the amplitude of
      the late afterhyperpolarization without affecting other aspects of the action
      potential or the resting potential. The firing frequencies of the neurons were
      enhanced by apamin over a range of depolarizing current pulse injections. The
      effect of apamin was also tested on fictive swimming, which was induced in the
      isolated spinal cord by bath application of an excitatory amino acid (D-glutamate
      or N-methyl-D,L-aspartate). A concentration of apamin (10 microM) sufficient to
      substantially reduce the late AHP had no significant effect on the ventral root
      burst rate, intensity, or phase lag during fictive swimming.

PMID- 1359471
TI  - Excitatory amino acid receptors involved in primary afferent-evoked polysynaptic
      EPSPs of substantia gelatinosa neurons in the adult rat spinal cord slice.
AB  - Intracellular recordings were made from substantia gelatinosa (SG) neurons in
      spinal cord slices to determine a subclass of excitatory amino acid receptors
      involved in polysynaptic excitatory postsynaptic potentials (EPSPs). In the
      majority of neurons, polysynaptic EPSPs evoked by A delta fiber were not affected
      by 2-amino-5-phosphonovaleric acid (APV), while all EPSPs including monosynaptic
      EPSPs were depressed by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). All
      spontaneous EPSPs were blocked by CNQX, while spontaneous EPSPs in a few SG
      neurons were attenuated by APV. These observations suggest that polysynaptic
      EPSPs evoked through A delta fibers are predominantly mediated by activation of
      the non-N-methyl-D-aspartate (non-NMDA) receptor subclass.

PMID- 1359472
TI  - Expression of the dopaminergic phenotype in the olfactory bulb: neither
      calcitonin gene-related peptide nor olfactory input is necessary.
AB  - In the olfactory bulb, expression of tyrosine hydroxylase (TH) in juxtaglomerular
      neurons is dependent on innervation by the olfactory nerve. The presence of the
      neuropeptide calcitonin gene-related peptide (CGRP) within the olfactory nerve
      has led to the hypothesis that CGRP is responsible for regulation of TH
      expression in the bulbar neurons. On the other hand, other investigators claim
      that olfactory receptors never produce CGRP and that functional contact with
      olfactory axons regulates production of TH by bulbar neurons. Two different
      experimental procedures were used to test whether either CGRP or contact with the
      olfactory nerve is essential for production of TH by bulbar neurons in vivo. The
      peptidergic innervation of the olfactory bulb was eliminated either by neonatal
      capsaicin treatment, or by stereotaxic, electrolytic lesions of the ophthalmic
      division of the trigeminal nerve. Both of the treatments leave the olfactory
      innervation of the bulb intact while eliminating the CGRP-immunoreactive fibers
      in the olfactory nerve and glomeruli. Subsequent immunocytochemistry reveals a
      normal complement of bulbar TH-immunoreactive juxtaglomerular neurons in the
      absence of peptidergic innervation. In order to test whether olfactory nerve
      input is necessary for expression of TH in vivo, the anlage of the olfactory bulb
      was removed from embryonic (E16) rat pups and transplanted into the anterior
      chamber. These ectopic olfactory bulbs, although devoid of olfactory nerve input,
      contain numerous TH-immunoreactive neurons. Thus olfactory nerve input is not
      necessary for expression of TH in bulbar neurons.

PMID- 1359473
TI  - Quisqualic acid-induced neurotoxicity is protected by NMDA and non-NMDA receptor
      antagonists.
AB  - Quisqualic acid-mediated excitotoxicity has been attributed essentially to the
      activation of non-N-methyl-D-aspartate (non-NMDA) receptors. In the present study
      we demonstrate the possible involvement of both NMDA and non-NMDA receptors in
      quisqualic acid-induced toxicity in mouse brain slices, in vitro. Incubation of
      mouse brain sagittal slices with various concentrations of quisqualic acid
      resulted in significant increase in the leakage of lactate dehydrogenase and
      potassium from the slices into the medium. Prior incubation of mouse brain slices
      with NMDA (MK-801 or AP7) or non-NMDA receptor antagonists (GDEE or
      quinoxalinediones) protected against quisqualic acid-mediated toxicity. Slices
      prepared from animals pretreated in vivo with MK-801 (5 mg/kg b.wt.) were also
      resistant to the toxic effects of quisqualic acid, indicating the possible
      involvement of NMDA receptors in quisqualic acid toxicity.

PMID- 1359474
TI  - Neuropeptide FF is colocalized with catecholamine-synthesizing enzymes in neurons
      of the nucleus of the solitary tract.
AB  - Neuropeptide FF (NFF) is an amidated octapeptide of bovine origin. It has some
      antiopioid-like effects and it elevates blood pressure when injected
      intravenously in rats. NFF-immunoreactive nerve cells and terminals are localized
      in large numbers in the dorsomedial caudal brainstem which is a region involved
      in central regulation of blood pressure. We compared the localization of NFF
      immunoreactive neurons with medullary catecholamine-synthesizing neurons by using
      immunohistochemical double-labeling and light microscopic mirror methods. NFF and
      tyrosine hydroxylase coexisted in a minor portion of the NFF neurons in the
      nucleus of the solitary tract and occasional cell bodies were stained with both
      NFF and PNMT (phenylethanolamine N-methyltransferase) antisera. The results have
      anatomical correlation with previous pharmacological reports, suggesting that NFF
      is present in neuronal systems involved in cardiovascular reflex arcs.

PMID- 1359476
TI  - Production of specific antibody against L-dopa and its ultrastructural
      localization of immunoreactivity in the house-shrew (Suncus murinus) lateral
      habenular nucleus.
AB  - An antiserum was raised against L-DOPA bound to bovine serum albumin, purified by
      affinity chromatography, and its specificities were verified by immunoblotting
      and enzyme-linked immunosorbent assays. The antiserum did not cross-react with
      dopamine (DA), tyrosine, tyramine, octopamine, norepinephrine or epinephrine.
      Immunocytochemical studies using the PAP method revealed that tyrosine
      hydroxylase- and L-DOPA positive but aromatic L-amino acid decarboxylase- and DA
      negative neurons were present in the lateral habenular nucleus of the house-shrew
      (Suncus murinus) brain. Ultrastructurally L-DOPA immunoreactive products were
      localized in the cytoplasmic matrix and terminals with vesicles.

PMID- 1359475
TI  - A novel inhibitor of glutamate release reduces excitotoxic injury in vitro.
AB  - Excessive release of glutamate has been implicated in the pathogenesis of
      excitotoxic neurologic disorders, such as stroke. BW 1003C87, an inhibitor of
      glutamate release and a putative Na+ channel antagonist, reduced veratridine
      stimulated, tetrodotoxin- and dizocilpine-sensitive toxicity (measured by lactate
      dehydrogenase efflux) in neuron-enriched cortical cultures (IC50 = 5 microM). In
      contrast, BW 1003C87 (300 microM) had no effect on toxicity induced by direct
      application of 1 mM glutamate or 1 mM N-methyl-D-aspartate, or by depolarization
      with 50 mM KCl. Glutamate release inhibitors such as BW 1003C87 may provide a
      novel approach to protection from excitotoxicity.

PMID- 1359477
TI  - EPSPs in rat neocortical pyramidal neurones in vitro are prolonged by NMDA
      receptor-mediated currents.
AB  - We investigated the influence of 2-amino-5-phosphonovalerate (APV), a selective
      antagonist of the N-methyl-D-aspartate (NMDA) receptor, on the time course of
      small excitatory postsynaptic potentials (EPSPs) in pyramidal neurones in layer
      2/3 of adult rat visual cortex in vitro. Time constants of the voltage decay
      following the EPSPs (T(s)) and after brief (2 ms) pulses of current injected at
      the soma (T(p)) were determined from semilogarithmic plots of averages of 100-250
      trials. The mean T(s)/T(p) ratio decreased from 1.53 +/- 0.29 (S.D.) to 1.10 +/-
      0.08 on addition of 50 microM APV to the bathing medium (P less than 0.001; n =
      23), but there was no significant change in EPSP peak amplitude or rise-time.
      These results suggest that the time course of many small EPSPs, even at negative
      membrane potentials and in the presence of Mg2+, can be prolonged by NMDA
      receptor-mediated currents.

PMID- 1359478
TI  - Effects of hexamethonium on transmitter release from the rat phrenic nerve.
AB  - Hexamethonium (HEX) was applied to isolated transected diaphragm-phrenic nerve
      preparations of the rat in order to further elucidate the functional role of the
      presynaptic nicotinic autoreceptors. End-plate potentials (EPPs) and miniature
      end-plate potentials (MEPPs) were recorded from the neuromuscular junctions in
      the presence and absence of HEX to determine the relative effect of this
      nicotinic antagonist on end-plate sensitivity and evoked release. In this study
      we show that HEX enhances transmitter release for the first few stimuli, but this
      action is not maintained during a train-of-six stimulation. While these results
      support the hypothesis that transmitter released from the nerve terminal normally
      has a negative feedback effect by depressing transmitter release it is proposed
      that HEX also has secondary actions on the neuromuscular junction that are
      unrelated to autoreceptor blockage. The results with HEX suggests that the
      presynaptic receptors may differ pharmacologically from the postsynaptic
      receptors.

PMID- 1359479
TI  - Excitatory synaptic transmission mediated by NMDA and non-NMDA receptors in the
      superficial/middle layers of the epileptogenic human neocortex maintained in
      vitro.
AB  - Conventional intracellular recordings were made from regular-spiking cells
      located in layers II-IV to examine the involvement of excitatory amino acid
      receptors in synaptic transmission in epileptogenic human neocortical slices
      maintained in vitro. Extracellular stimuli that were below the threshold for
      generating action potentials evoked an excitatory postsynaptic potential (EPSP)
      with short latency to onset (0.8-4 ms). When suprathreshold stimuli were
      delivered, 95% of the neurons fired a single action potential. In 5% of the
      population, however, an all-or-none bursting discharge was observed. The EPSP and
      the bursting discharge were tested with the N-methyl-D-aspartate (NMDA)
      antagonist 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP, 5 microM)
      or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 4 microM).
      In the presence of CNQX the peak amplitude of the EPSP was reduced by 85% and the
      bursting discharge was abolished completely. By contrast, CPP reduced the peak
      amplitude of the EPSP by 52%, attenuated the late phase of the bursting discharge
      and increased its threshold. These results indicate that excitatory amino acids
      function as excitatory transmitters in the human brain. While the involvement of
      non-NMDA receptors in the EPSP is in line with data from normal neocortical
      slices of other mammals, the participation of NMDA-mediated conductances to the
      EPSP appears peculiar to the epileptogenic human neocortex. This evidence,
      together with the contribution of NMDA and non-NMDA receptors to the all-or-none
      bursting discharge suggests that excitatory amino acid-mediated transmission
      might be modified in the epileptogenic human neocortex.

PMID- 1359480
TI  - Inhibition by locus coeruleus on the baroreceptor reflex response in the rat.
AB  - We evaluated the modulation of baroreceptor reflex (BRR) response by locus
      coeruleus (LC) in adult, male Sprague-Dawley rats anesthetized with urethane (1.5
      g/kg, i.p.). Under an electrical stimulation condition that did not appreciably
      alter the basal systemic arterial pressure and heart rate, the LC significantly
      suppressed the BRR response. Microinjection of L-glutamate (1 nmol, 50 nl) into
      the LC essentially duplicated this depressant effect. Intracerebroventricular
      (i.c.v.) administration of the alpha 1-adrenoceptor antagonist, prazosin (6.5
      nmol), appreciably blunted the inhibition by LC on the BRR response. Yohimbine
      (6.5 nmol), the alpha 2-adrenoceptor blocker, however, was ineffective. Direct
      microinjection of prazosin (50 pmol), but not yohimbine (50 pmol), into the
      terminal site of baroreceptor afferents at the nucleus tractus solitarii (NTS)
      also significantly blunted the suppressive effect of LC on the BRR response.
      These results suggest that the LC may produce an inhibition on the BRR response
      by a process that involves the alpha 1-adrenoceptors located in the NTS.

PMID- 1359481
TI  - Expression of c-fos protein in the medulla oblongata of conscious rabbits in
      response to baroreceptor activation.
AB  - Neuronal expression of c-fos protein (Fos) in the medulla in response to
      baroreceptor activation was studied in conscious rabbits. Raising arterial
      pressure resulted in a marked increase, compared to control animals, in Fos
      immunoreactivity in the nucleus tractus solitarius, area postrema and
      ventrolateral medulla (VLM). Fos-immunoreactive neurons in the VLM extended from
      the level just rostral to the obex to 3 mm more caudal. Only a small proportion
      of these neurons showed tyrosine hydroxylase immunoreactivity. The results
      indicate that baroreceptor activation induces Fos expression in circumscribed
      medullary regions which have previously been shown to receive excitatory
      baroreceptor inputs.

PMID- 1359482
TI  - AIDS: advocacy & activism. Amsterdam I & II: orthodoxies and heresies.

PMID- 1359483
TI  - Aluminum inhibits glutamate release from transverse rat hippocampal slices: role
      of G proteins, Ca channels and protein kinase C.
AB  - Aluminum (Al) has been shown to produce deficits in learning and memory. The
      present experiments tested the hypothesis that Al-induced inhibition of learning
      may be due to its effect on glutamate release secondary to changes in calcium
      channel function and/or intracellular events triggering glutamate release.
      Calcium-dependent potassium (K)-evoked [14C]-glutamate release from 400 microns
      transverse rat hippocampal slices was inhibited by Al in a concentration
      dependent manner (IC50 = 40 microM). Aluminum (30, 100 microM) noncompetitively
      inhibited Bay K 8644-evoked glutamate release. 4-Aminopyridine (30, 1000 microM)
      noncompetitively attenuated the Al inhibition of glutamate release, suggesting an
      Al-induced alteration of Ca channel function. Activation of the Gi protein by R(
      )phenylisopropyladenosine (PIA; 1 microM) reduced K-evoked glutamate release 69%,
      whereas 300 microM Al produced an 84% reduction. These effects were prevented by
      the Gi protein inhibitor N-ethylmaleimide (NEM; 100 microM), suggesting an effect
      of Al on the Gi protein to inhibit glutamate release. Phorbol myristate acetate
      (0.16 microM)-induced glutamate release was inhibited by 300 microM Al and 80
      microM polymyxin B, suggesting an Al modulation of protein kinase C (PKC)-evoked
      glutamate release. These results demonstrate an Al inhibition of glutamate
      release that may be mediated by multiple, but interconnected mechanisms (e.g.,
      via interactions with Ca systems), providing multiple targets for an Al-induced
      alteration of neuronal function.

PMID- 1359484
TI  - Dynorphin A content in the rat brain and spinal cord after a localized trauma to
      the spinal cord and its modification with p-chlorophenylalanine. An experimental
      study using radioimmunoassay technique.
AB  - The distribution of dynorphin A in the spinal cord and brain of normal rats and
      of rats subjected to a focal injury of the spinal cord was examined in a rat
      model using a radioimmunoassay (RIA) technique. The validity of RIA was checked
      by high performance liquid chromatography (HPLC). Furthermore, the possibility
      that the peptide is somehow functionally related with endogenous 5
      hydroxytryptamine (5-HT, serotonin), was also evaluated using a pharmacological
      approach. In normal animals, the peptide content was very similar in the spinal
      cord segments (T9, T10-11, and T12) examined whereas, the dynorphin content of
      the whole brain was about two-fold higher compared with that in the spinal cord.
      A focal injury to the spinal cord in the right dorsal horn (about 1.5 mm deep,
      2.5 mm long and 1.5 mm to the right of the midline) of the lower thoracic cord
      (T10-11) in urethane anaesthetised animals significantly altered the peptide
      content in the whole brain as well as in the spinal cord. Thus, a decrease in the
      peptide level in whole brain, T10-11 and in the T12 segments of the spinal cord
      was observed 1 and 2 h after trauma. At 5 h, the peptide had accumulated markedly
      in the T9 segment (about a two-fold increase) as compared with the controls. At
      this time, the peptide content had been restored in the T10-11 and T12 segments.
      On the other hand, the whole brain dynorphin level continued to remain low (by
      55%) as compared to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359485
TI  - Extrapyramidal symptoms are serious side-effects of antipsychotic and other
      drugs.
AB  - Antipsychotic medications commonly produce extrapyramidal symptoms as side
      effects. The extrapyramidal symptoms include acute dyskinesias and dystonic
      reactions, tardive dyskinesia, Parkinsonism, akinesia, akathisia, and neuroleptic
      malignant syndrome. Extrapyramidal symptoms are caused by dopamine blockade or
      depletion in the basal ganglia; this lack of dopamine often mimics idiopathic
      pathologies of the extrapyramidal system. Less recognized is that extrapyramidal
      symptoms are also associated with certain non-antipsychotic agents, including
      some antidepressants, lithium, various anticonvulsants, antiemetics and, rarely,
      oral-contraceptive agents. Extrapyramidal symptoms caused by these agents are
      indistinguishable from neuroleptic-induced extrapyramidal symptoms. Clinicians
      must be able to recognize these side effects and be able to determine the
      antipsychotic-induced and non-antipsychotic causes of extrapyramidal symptoms.

PMID- 1359486
TI  - AIDS.

PMID- 1359487
TI  - Localization of alpha-2 adrenergic receptors in the human eye.
AB  - To elucidate sites of the action of alpha-2 adrenergic drugs, we localized
      binding sites for a potent alpha-2 adrenergic agonist, UK-14,304, in sections of
      the human cadaveric eye by an in vitro ligand-binding technique and
      autoradiography. Its specific binding sites were found in the iris epithelium and
      ciliary epithelium at a high level, and also in the ciliary muscle, retina,
      retinal pigment epithelium (and/or choroid). Binding of UK-14,304 to the ocular
      pigments was prevented by preincubating the eye sections with chloroquine, which
      reduced the non-specific binding to a low level.

PMID- 1359488
TI  - Simple and accurate assay for tyrosine hydroxylase from bovine retina by high
      performance liquid chromatography with fluorescence detection.
AB  - We present a simple and sensitive assay for tyrosine hydroxylase (TH) using high
      performance liquid chromatography (HPLC) with a fluorescence detector which
      enabled us to study bovine retinal TH of a small quantity in crude retinal
      samples. The detection limit with this method was 1 pmol of
      dihydroxyphenylalanine (DOPA) enzymatically produced. Retinal TH exhibited the
      maximum activity at pH 6 to 6.3, and almost none at physiological pH of above 7,
      a tendency similar to that reported for striatal TH.

PMID- 1359489
TI  - Contraindications to vasoconstrictors in dentistry: Part III. Pharmacologic
      interactions.
AB  - This article discusses the relative contraindications to the use of
      vasoconstrictor in patients currently medicated with tricyclic antidepressants,
      monoamine oxidase inhibitors, phenothiazines and beta-blockers. It reviews drug
      interactions and emphasizes potential detrimental systemic effects that
      epinephrine contained in local anesthetics can have when administered
      concomitantly with these drugs. Finally, special considerations are expressed
      concerning patients who abuse illicit drugs such as cocaine.

PMID- 1359490
TI  - [Ocular manifestations in porphyria cutanea tarda].
AB  - Ninety two patients suffering from porphyria cutanea tarda were examined
      ophthalmologically in a paired case-control study. The incidence of pinguecula
      and that of pterygium were 8 times and 2 times higher, respectively, in PCT
      patients that in the control group. The photodamage of the conjunctiva is
      presumed to be a result of the photoactivity of uroporphyrin in the tissues.

PMID- 1359491
TI  - [Effectiveness and safety of long-term H2-receptor antagonist maintenance
      therapy].
AB  - The long-term maintenance therapy with an H2 receptor antagonist is currently the
      best treatment for ulcer disease. The treatment is effective in keeping most
      ulcers in remission, and is safe both by preventing ulcer complications and
      because the treatment itself is innocuous. Maintenance therapy achieves the
      objective of all treatment--it restores patients to normal health. Treatment of
      ulcer disease with an H2 receptor antagonist can be considered one of the
      triumphs of modern therapy.

PMID- 1359493
TI  - p53 mosaicism with an exon 8 germline mutation in the founder of a cancer-prone
      pedigree.
AB  - Changes in the tumor-suppressor gene p53 are frequently acquired during the
      course of malignant development of human tumors. Recently, constitutional
      heterozygous mutations in p53 exon 7 have been identified as the primary cause of
      cancer predisposition in cases of the familial Li-Fraumeni cancer syndrome. These
      findings underline the need for extensive mutation screening in families with
      high cancer incidence. This report describes the detection and follow-up by two
      dimensional single-strand conformation polymorphism analysis (2DSSCP) of a new
      germline mutation of p53 exon 8 in a case of suspected Li-Fraumeni syndrome.
      Although a high cancer incidence had been reported in the family history of the
      father of siblings suffering from brain tumor and rhabdomyosarcoma, a
      constitutional heterozygous p53 mutation was identified only in the affected
      children. Retrospective analysis of archival tissue of a half-sister who died
      several years ago from a tumor of previously uncertain diagnosis revealed the
      same mutation. The mutation had therefore occurred in the germ cells of the
      mother, who thus appears to be a mosaic. The cancer predisposition of the
      paternal ancestors must have been due to other factors.

PMID- 1359492
TI  - HTLV-I and HTLV-II tax trans-activate the human EGR-1 promoter through different
      cis-acting sequences.
AB  - The immediate-early response gene, EGR-1, encodes a zinc finger-containing
      transcription factor that is involved in growth and differentiation of a variety
      of cell types. EGR-1 is induced in normal T cells following mitogenic stimulation
      and has recently been shown to be constitutively expressed in human T-cell
      leukemia virus type I (HTLV-I)- and type II (HTLV-II)-transformed T-cell lines.
      The trans-activating protein of HTLV-I, Tax, has been demonstrated to trans
      activate promoters of a number of cellular genes, some of which may be critical
      in regulating T-cell proliferation. In this study, we examine the effect of Tax
      on expression of EGR-1 in three T-cell lines and demonstrate that both HTLV-I and
      -II Tax are capable of trans-activating human EGR-1 recombinant promoter
      constructs. Interestingly, HTLV-I and -II Tax trans-activate the human EGR-1
      promoter through different promoter regions in the Jurkat cell line, suggesting
      that HTLV-I and -II Tax may lead to constitutive expression of EGR-1 through
      different signaling pathways. Deregulated expression of EGR-1 may contribute to
      uncontrolled cell growth and transformation during early stages of T-cell
      activation in HTLV-I and -II-infected cells.

PMID- 1359494
TI  - The insulin-like growth factor 1 receptor is required for the proliferation of
      hemopoietic cells.
AB  - We have investigated the role of the insulin-like growth factor one (IGF1)
      receptor and its relationship to the proto-oncogene c-myb in the growth of two
      types of hemopoietic cells: mitogen-stimulated human peripheral blood mononuclear
      cells and a human promyelocytic cell line (HL-60). Using the antisense strategy
      and the reverse transcriptase polymerase chain reaction (RT-PCR), we show that
      expression of the IGF1 receptor is required for the entry into S phase of both
      stimulated lymphocytes and HL-60 cells. The inhibition of DNA synthesis by
      antisense oligomers to the IGF1 receptor RNA is accompanied by an inhibition of
      the expression of the mRNA for a DNA synthesis gene, proliferating cell nuclear
      antigen (PCNA), the co-factor of DNA polymerase delta. Inhibition of c-myb
      expression results in a decrease in IGF1 receptor mRNA levels; on the other hand,
      inhibition of IGF1 receptor expression has no effect on c-myb mRNA levels. A
      tentative temporal relationship between these three genes (c-myb, IGF1 receptor,
      PCNA) is proposed.

PMID- 1359495
TI  - Mechanisms of c-erbB2/neu oncogene-induced metastasis and repression of
      metastatic properties by adenovirus 5 E1A gene products.
AB  - c-erbB2/neu is a transforming oncogene that encodes a 185-kDa transmembrane
      glycoprotein. In many but not all studies, amplification and/or overexpression of
      the human c-erbB2/neu oncogene has been correlated with poor prognosis and the
      number of lymph node metastases in node-positive breast cancer patients. We have
      shown that expression of the activated rat c-erbB2/neu oncogene in mouse embryo
      fibroblast 3T3 cells is sufficient to induce experimental metastases in nude
      mice. Important steps in the metastatic event are tumor cell adhesion to
      endothelial cells and invasion of basement membranes. Therefore, we further
      examined the ability of c-erbB2/neu oncogene-transformed 3T3 cells to adhere to
      microvessel endothelial cells and secrete basement membrane-degradative enzymes.
      The c-erbB2/neu oncogene-transformed 3T3 cells were shown to be more adherent and
      have higher gelatinase activities. Since we had previously shown that the
      adenovirus 5 E1A gene product can suppress c-erbB2/neu-induced transformation of
      3T3 cells, we examined the possibility that E1A can abrogate the metastatic
      properties of c-erbB2/neu-transformed 3T3 cells. We found that introduction of
      the E1A gene into c-erbB2/neu-transformed 3T3 cells reduced the formation of
      experimental metastatic tumors and inhibited metastasis-associated properties,
      such as adhesion to microvessel endothelial cells, migration through a layer of
      reconstituted basement membrane (Matrigel) and secretion of basement membrane
      degradative enzymes. The results indicate that the mechanism by which the c
      erbB2/neu gene induces higher metastatic potential is to promote adhesion and
      invasion steps of the metastatic cascade. The E1A gene, which functions by
      inhibiting these steps, is thus a suppressor gene for c-erbB2/neu-induced
      experimental metastasis.

PMID- 1359496
TI  - Bureau looking for AIDS-like illnesses.

PMID- 1359497
TI  - [Stress related immune regulation].
AB  - The immune system ist capable of producing factors, which apart from playing a
      crucial role during the immune response, serve to integrate immune-neuroendocrine
      circuits with immunoregulatory and metabolic consequences for the organism.
      Hormones and neuropeptides on the other hand exert direct effects on immune cells
      via specific surface receptors on such cells. Therefore, there is strong evidence
      for a bidirectional communication between the immune, endocrine, and central
      nervous systems mediated by peptide hormones and receptors common to these
      systems. One element of the immune system's response to stress factors may
      involve the activation of the hypothalamo-pituitary-adrenal axis and other
      neuroendocrine circuits. A complex network of neuroendocrine immune systems is
      able to sustain biologic adaptation and homeostasis in response to stresses and
      needs to be taken into account in every clinical context of stress responses.

PMID- 1359498
TI  - Identification and quantification of rodent malaria strains and species using
      gene probes.
AB  - A DNA probe PCsv4 and a subclone thereof PCsv4.1, hybridize specifically to
      rodent malaria DNA. DNA purified from a small volume (10 microliters) of infected
      mouse blood was used to determine the composition of the parasite population
      present. The hybridization signal following PCsv4 probing of slot-blotted DNA
      correlated directly with parasitaemia. The hybridization pattern and intensity,
      resulting from probing restriction enzyme digested and Southern-blotted genomic
      DNA, determined the identity of the infecting parasite line(s), and provided a
      semi-quantitative measure of parasite burden. Fifteen parasite lines
      representative of all four Plasmodium species infecting rodents can be
      differentiated in this way.

PMID- 1359499
TI  - Asthma, allergies, and school.

PMID- 1359500
TI  - Cystic fibrosis manifested as undescended testis and absence of vas deferens.

PMID- 1359501
TI  - Malignant vasovagally mediated hypotension and bradycardia: a possible cause of
      sudden death in young patients with asthma.

PMID- 1359502
TI  - Longitudinal follow-up of malignant osteopetrosis by skeletal radiographs and
      restriction fragment length polymorphism analysis after bone marrow
      transplantation.

PMID- 1359503
TI  - [Molecular genetics and prenatal diagnosis].
AB  - Recombinant DNA techniques have provided new insight into genetic and prenatal
      diagnosis during the last 10 years. Human gene mapping data are increasing
      exponentially due to molecular biology advances. Most analyses are possible from
      chorionic villi biopsy specimens as early as the 10th week of fetal life. When
      the gene is known and cloned, the diagnosis is regularly made by using the
      polymerase chain reaction technique; when the gene is unknown but mapped, the
      restriction fragment length polymorphism technique is used. However, these
      methods for prenatal assessment require a reliable diagnosis of index case
      disease and a preliminary familial DNA study.

PMID- 1359504
TI  - A drug use review study in patients with obstructive lung disease. Assessment of
      the quality of drug therapy.
AB  - This study presents the results of an analysis of the pharmacy records of 778
      patients with asthma or chronic obstructive lung diseases. The high percentage of
      patients taking oral corticosteroids was striking. Inhaled beta-agonists for use
      as needed have been prescribed to only a minority of patients using these agents.
      Only half of the patients on beta-agonists used inhaled corticosteroids
      prophylactically. Drug interactions capable of causing changes in plasma
      theophylline concentrations appeared in only a small number of patients. The
      results from studies like the one presented here can provide valuable data to be
      used for further discussion between physicians and pharmacists about rational
      drug therapy.

PMID- 1359506
TI  - The sustained development of preneoplastic lesions depends on high protein
      intake.
AB  - The effects of sequential alterations in the feeding of two levels of dietary
      protein (5% and 20% casein) on the postinitiation development of aflatoxin B1-
      (AFB1) induced gamma-glutamyl transpeptidase-positive (GGT+) preneoplastic foci
      were examined. Weanling male Fischer 344 rats fed AIN-76A diet (20% protein) were
      administered 10 intragastric doses of AFB1 (1 dose/day during the 14-day dosing
      period excluding weekends) at 250 micrograms/kg body wt (initiation). After AFB1
      tissue clearance, rats were randomly assigned to dietary treatment groups. During
      the next 12 weeks (promotion), they developed AFB1-induced GGT+ preneoplastic
      lesions. The 12-week promotion period was subdivided into four three-week
      periods, during which rats were fed isocaloric diets containing 20% casein during
      all four periods (20:20:20:20), 5% casein during all four periods (5:5:5:5), or
      sequentially altered casein levels (20:5:20:5 and 5:20:5:20). Rats were killed at
      3,6,9, and 12 weeks to examine the dependence of GGT+ foci development on protein
      intake. Animals fed 5% casein diets developed significantly fewer (p < 0.01) GGT+
      foci than animals fed 20% casein diets despite greater total caloric intake.
      Similarly, in the intervention groups, preneoplastic development was enhanced
      when the 20% casein diet was fed and inhibited when the 5% casein diet was fed.
      These results indicate that the sustained development of AFB1-induced
      preneoplastic foci depends on a high protein intake. Alternatively, these results
      suggest that low protein intake inhibits lesion development.

PMID- 1359505
TI  - PCNA-induced DNA synthesis past cis-syn and trans-syn-I thymine dimers by calf
      thymus DNA polymerase delta in vitro.
AB  - Calf thymus proliferating cell nuclear antigen (PCNA) promoted DNA synthesis past
      cis-syn and trans-syn-I cyclobutane thymine dimers by calf thymus DNA polymerase
      delta (Pol delta) in vitro. Templates containing site-specific cis-syn and trans
      syn-I thymine dimers were prepared via a combination of solid phase synthesis
      with photoproduct building blocks and DNA ligation. Extension of a 15-mer primer
      on the UV dimer-containing templates by Pol delta produced termination and bypass
      products in a dNTP and PCNA dependent manner. In the absence of PCNA and at dNTP
      concentrations varying between 1 and 100 microM, Pol delta could not bypass the
      cis-syn dimer and terminated elongation one nucleotide prior to the 3'-T of the
      dimer. DNA synthesis past the trans-syn-I dimer was even less efficient. In the
      presence of PCNA, termination occurred primarily one nucleotide prior to the 3'-T
      of both dimers at 1 microM dNTPs but opposite the 5'-T of the dimers at 100
      microM dNTPs. In addition, under the latter conditions, bypass of the dimers was
      observed, to the extent of about 30% of the products for the cis-syn dimer and
      about 15% for the trans-syn-I dimer.

PMID- 1359507
TI  - Isolation of a novel tetrapeptide with opiate and antiopiate activity from human
      brain cortex: Tyr-Pro-Trp-Gly-NH2 (Tyr-W-MIF-1).
AB  - A novel tetrapeptide, Tyr-Pro-Trp-Gly-NH2 (Tyr-W-MIF-1), was purified from
      extracts of frontal cortex of human brain tissue by several consecutive reversed
      phase high performance liquid chromatographic steps followed by a
      radioimmunoassay originally developed for Tyr-Pro-Leu-Gly-NH2 (Tyr-MIF-1).
      Sequencing, mass spectrometric analysis, and comparison of its chromatographic
      behavior with that of the synthetic peptide confirmed the structure. Like Tyr-MIF
      1, which was previously isolated from human brain tissue, Tyr-W-MIF-1 can inhibit
      the binding of 3H-DAMGO (selective for mu opiate receptors) to rat brain and can
      act as an opiate agonist as well as antagonist. Tyr-W-MIF-1 was a more potent
      opiate agonist than Tyr-MIF-1, the free acid of Tyr-W-MIF-1, and the structurally
      related hemoglobin-derived opiate peptide hemorphin-4 (Tyr-Pro-Trp-Thr) in the
      guinea pig ileum. Each of these peptides acted as opiate antagonists on the ileum
      from morphine-tolerant guinea pigs; the free acid of Tyr-W-MIF-1 was the most
      potent antagonist in inhibiting the activity of DAMGO. The results demonstrate
      the presence in human brain of a new member of the Tyr-MIF-1 family of
      biologically active peptides.

PMID- 1359508
TI  - Neuroanatomical connections between corticotropin-releasing factor (CRF) and
      somatostatin (SRIF) nerve endings and thyrotropin-releasing hormone (TRH) neurons
      in the paraventricular nucleus of rat hypothalamus.
AB  - In order to investigate the possible involvement of corticotropin-releasing
      factor (CRF) and somatostatin (SRIF) on thyrotropin-releasing hormone (TRH)
      neuronal cell activity in the rat hypothalamic paraventricular nucleus, we have
      proceeded to the simultaneous localization of CRF or SRIF and TRH. For this
      purpose, we used a dual immunostaining procedure that employed antibodies to CRF
      and SRIF and peroxidase-labeled goat anti-rabbit IgG as a first sequence, and
      antibodies to a cryptic fragment (Phe178-Glu199) of pro-TRH (to label TRH
      neurons) and alkaline phosphatase-labeled goat anti-rabbit IgG as the second
      sequence. A rich innervation of the paraventricular nucleus by immunoreactive CRF
      and SRIF fibers was observed. A large number of CRF and SRIF nerve endings were
      seen intimate anatomic proximity and often appeared to surround TRH-containing
      cell bodies. These results strongly suggest that TRH neurons might be regulated
      by both CRF and SRIF. These interactions might be the neuroanatomical basis for
      the already observed inhibitory effects of CRF and SRIF on TRH release.

PMID- 1359509
TI  - Identification of neuropeptide-degrading enzymes in the pancreas.
AB  - Neutral endopeptidase (NEP) and aminopeptidase M (APM) were identified in the
      pancreas by enzymatic assays and Western blotting. The NEP activity, assessed by
      the phosphoramidon- and DL-thiorphan-inhibitable degradation of glutaryl-Ala-Ala
      Phe-4-methoxy-2-naphthylamine, was 28.8 pmol/h/micrograms of pancreatic membrane
      protein and 124 pmol/h/10(6) pancreatic acinar cells. The APM enzymatic activity,
      assessed by the actinonin- and amastatin-inhibitable degradation of Ala-4-methoxy
      2-naphthylamine, was 633 pmol/h/micrograms pancreatic membrane protein and 17.4
      nmol/h/10(6) pancreatic acinar cells. Proteins corresponding to NEP (95 kDa) and
      APM (140 kDa) were identified in membranes by Western blotting. Both NEP and APM
      on acinar cells may degrade neuropeptides and regulate their effects on exocrine
      secretion.

PMID- 1359510
TI  - Blockade of dynorphin A(1-13) overt psychomotor effects by naloxone.
AB  - Each of the dynorphin A(1-13) or dynorphin (dyn) treatment groups receiving
      naloxone showed a significant overall reduction of overt signs compared with the
      dyn controls. The data suggested that the overt psychomotor effects of dyn in the
      rhesus monkey were especially prone to blockade by naloxone, and probably
      involved opioid mechanisms.

PMID- 1359511
TI  - [Molecular biology of the atrial natriuretic factor].

PMID- 1359512
TI  - [Migraine as one of the symptoms of food allergy].
AB  - A role of nutrients in the onset of migraine and other gastrointestinal symptoms
      (vomiting, nausea, diarrhoea), skin reactions (rush, atopic dermatitis, Quincke'a
      edema), respiratory symptoms (bronchial asthma, cough, allergic rhinitis, polyps,
      congestion of the nasal mucosa), motion system disorders (jointache and edema),
      gynecological disorders (chronic and recurrent adnexitis), and sleep disorders
      together with emotional tension and behavioral disturbances has been assessed in
      17 patients with atopy. Migraine attacks have been produced most frequently by
      cow milk (in 10 out of 17 patients), cabbage, flour and eggs in 5 patients,
      preservatives, cottage and Swiss cheese, porcine meat in 4 patients, colorants
      and chocolate in 3 patients, beef, strawberries, lemons and butter in 2 patients.
      Other nutrients produced headache in single patients. Migraine and other symptoms
      have diminished after an individual elimination diet. Recurrence has been noted
      after each consumption of allergen except one female patient with EEG
      abnormalities. Immunoglobulins E have been involved in headache-producing
      mechanism in 3 patients.

PMID- 1359513
TI  - [Use of molecular DNA probes in the diagnosis of mucoviscidosis-- analysis of
      restriction fragment length polymorphisms (RFLP) in 22 high-risk families].
AB  - The results of DNA analysis with the aid of specific molecular probes are
      discussed. DNA analysis involved 22 families of a high risk of cystic fibrosis. A
      significance of the obtained results in genetic counselling is also discussed.
      DNA analysis enabled detection or exclusion of cystic fibrosis gene carrier state
      in patient's relatives. DNA analysis proved fully informative in case of 17
      families being a base to offer these families prenatal diagnosis of the disease
      in the I trimester of pregnancy, if such a family plans conception, and to accept
      this diagnostic technique.

PMID- 1359514
TI  - [Current theories on the etiology and treatment of Gilles de la Tourette's
      disease].
AB  - Gilles de la Tourette syndrome is a condition marked by: (1) onset usually in
      childhood and adolescence, i.e. between 2 and 15 years of life; (2) violent
      facial tics and echolalia; (3) increased excitability and apathy; (4) progressive
      increase in symptoms intensity; (5) chronic course. This syndrome is threefold
      more frequent in men than in women. None hypothesis concerning its
      etiopathogenesis (genetic, organic, organic-functional, psychomotor, and mixed)
      does explain its origin. Many cases respond with some degree of relief to
      neuroleptics, carbamazepine, clonidine, and glucocorticosteroids. Neurosurgery
      and psychotherapy are also of value. Haloperidol is commonly considered the most
      effective in this syndrome.

PMID- 1359515
TI  - Effect of acute and chronic treatment of rats with the putative anxiolytic drug
      ipsapirone on the turnover of monoamine transmitters in various brain regions. A
      comparison with the 5-HT1A agonist 8-OH-DPAT.
AB  - A fourteen-days treatment (twice a day) of male Wistar rats with the putative
      anxiolytic ipsapirone (10 mg/kg po) and the selective 5-HT1A agonist 8-OH-DPAT (1
      mg/kg ip) induced changes in the turnover of serotonin and catecholamines in
      various regions of the brain. In contrast to 8-OH-DPAT, ipsapirone stimulated the
      development of tolerance in serotonin neurons in the hypothalamus, hippocampus,
      cortex and striatum. Nevertheless, adaptative changes were not produced by
      ipsapirone in dopamine neurons in the striatum or nucleus accumbens, or in
      noradrenaline neurons in the hypothalamus, hippocampus or cortex. The centrally
      active metabolite of ipsapirone 1-PP, which has adrenolytic properties, seems to
      be responsible for the effects on the dopamine and noradrenaline turnover.

PMID- 1359517
TI  - XI Congress of the Polish Pharmacological Society with cooperation of the German
      Society of Pharmacology and Toxicology. Gdansk, September 16-19, 1992. Abstracts.

PMID- 1359516
TI  - Structure-activity relationship studies of CNS agents. Part III. On the bioactive
      conformations of 1-arylpiperazines at 5-HT1A receptor.
AB  - Quantitative structure-activity relationships (QSAR) were analyzed for 5-HT1 and
      5-HT1A affinity data of two series of 1-arylpiperazines. A conformational
      analysis of the investigated derivatives was performed using CNDO/2 method. It
      was shown that some 1-arylpiperazines adopt the bioactive conformations, while
      the others, like 1-(2-alkylphenyl)-piperazines, should exist in the twisted
      conformations at the receptor sites.

PMID- 1359518
TI  - Exercise and hypertension. Maximizing the benefits in patients receiving drug
      therapy.
AB  - Aerobic exercise may prevent hypertension and reduce blood pressure and mortality
      in hypertensive patients and those at high risk for coronary artery disease.
      Supervised aerobic exercise at an intensity of 70% to 80% of maximal aerobic
      capacity is recommended to achieve cardiovascular conditioning and other health
      benefits. When antihypertensive drug therapy is required, physicians should
      choose an agent that has favorable secondary effects, including hemodynamic
      responses to exercise. The most favorable effects are achieved with calcium
      channel blockers, angiotensin-converting enzyme inhibitors, alpha blockers, and
      central alpha agonists. The effects of diuretics are less desirable, and beta
      blockers should be a last choice for hypertensive patients who are physically
      active.

PMID- 1359519
TI  - Asthma in the 1990s. A new approach to therapy.
AB  - Asthma has been shown to be an inflammatory disease. Therefore, it makes sense to
      base treatment strategies on the selection of an appropriate anti-inflammatory
      agent, with bronchodilators being used as effective rescue medications. Because
      of recent concerns raised in the literature about the safety of long-term use of
      beta 2 agonists, early and appropriate medication in the form of inhaled
      corticosteroids or cromolyn sodium is recommended for daily control of asthma
      symptoms, long-term patient management, and prevention of acute exacerbations.

PMID- 1359521
TI  - Pruritus. What to do when the itching won't stop.
AB  - Pruritus is a common problem that can result from many conditions. Some, such as
      fungal or parasitic infection, may be fairly obvious. However, others, such as
      iron deficiency and psychogenic disorder, are more difficult to diagnose.
      Evaluation must include a thorough inspection of the skin, history taking for
      drug intake and chemical exposure, and appropriate laboratory testing. The
      location on the body and characteristics of the itching may point to a cause. In
      some cases, attention to exacerbating factors (eg, dry skin, coarse fabrics
      against the skin, dry environmental conditions) and application of topical
      preparations may be sufficient. Antihistamines are the foundation of oral
      treatment, and with the advent of second-generation agents, they can be taken
      with fewer concerns about their sedative effects. Specific conditions of which
      pruritus is one feature may require specific treatment. For example, in patients
      undergoing dialysis, activated charcoal, UV light treatment, or heparin therapy
      may be useful.

PMID- 1359520
TI  - Outpatient management of inflammatory bowel disease. Let's keep it as simple as
      possible.
AB  - Inflammatory bowel disease is a conglomeration of disorders of unclear etiology
      and pathogenesis. Confirming the diagnosis of active disease may be difficult but
      is critical to judicious therapy. Sulfasalazine (Azulfidine) and its newer
      derivatives mesalamine (Asacol, Rowasa) and olsalazine sodium (Dipentum) are used
      for treatment of mild disease and maintenance. Corticosteroid therapy controls
      moderate disease in most patients, but withdrawal may be difficult.
      Immunosuppression or surgery may be necessary in severe or refractory cases. The
      risk of cancer as a complication of inflammatory bowel disease is often
      exaggerated but cannot be ignored.

PMID- 1359522
TI  - Monozygotic twins concordant for both open-angle glaucoma and bronchospasm
      induced by beta-blockers.

PMID- 1359523
TI  - B-HT 920-induced effects on rat feeding behaviour.
AB  - Wistar rats, deprived of food for 15 h, were injected with B-HT 920 and 20 min
      later presented with their normal diet in their individual home cages. The
      parameters considered were latency to feeding and food intake which was
      determined 0.5, 1, 2, 3, 6 and 24 h later. B-HT 920 significantly reduced latency
      to feeding at 0.1, 0.5 and 1 mg/kg; food intake was increased by doses of 0.05
      and 0.1 mg/kg 3 and 6 h after treatment and decreased by a dose of 1 mg/kg at 3
      h. The amount of food eaten over a 24 h period by the various groups did not
      differ. At this time rats received a second injection of the drug at the same
      dosages, and preweighed food was presented again 20 min later. We confirmed that
      latency to feeding is lowered by B-HT 920 at 0.1, 0.5 and 1 mg/kg, doses which
      also induced feeding in sated rats within the first half-hour and even after 1 h
      in the case of the highest dose. Since penile erection and stretching and
      yawning, signs typically induced by all DA D2 agonists, were observed after B-HT
      920 at 0.05, 0.1 and 0.5 mg/kg, discussion centres on the possible mechanisms
      involved in the B-HT 920-induced effects.

PMID- 1359524
TI  - The fate of altered hepatocytic foci as a result of treatment with oxodipine, a
      calcium channel blocker.
AB  - The dietary administration of the calcium channel blocker oxodipine to Fischer
      (F344) rats for 12 and 30 months resulted in increased incidence of altered
      hepatocytic foci (AHF). As the Environmental Protection Agency (EPA) regards AHF
      as potentially precancerous it is important to accumulate experimental evidence
      which may negate this theory. In the case of oxodipine we proved that with
      dosages close to maximum tolerated dose (MTD) for prolonged periods no hepatic
      neoplasms were produced. The possible nature of such AHF is discussed.

PMID- 1359525
TI  - A novel peptide toxin from Trimeresurus wagleri acts pre- and post-synaptically
      to block transmission at the rat neuromuscular junction.
AB  - The neuromuscular effects of a peptide toxin (peptide I) from venom of
      Trimeresurus wagleri were investigated using the rat extensor digitorum longus
      muscle/peroneal nerve preparation. Sub-micromolar concentrations depressed
      endplate currents (EPCs) produced in response to nerve stimulation. Since quantal
      content of EPCs was not altered, it appears that the site of action is post
      synaptic. However, higher concentrations (1.4-2.9 microM) also inhibited
      spontaneous release of transmitter. Nerve stimulation in the presence of peptide
      I caused 'rundown' of EPC amplitude, evidence that the peptide acts pre
      synaptically to interfere with transmitter release. Recovery from this effect
      occurred within 3-5 min. of washing, but EPC amplitude took 20-30 min. to
      recover. The dual action of this peptide makes it unusual amongst naturally
      occurring toxins, and these data suggest that further investigation of the
      peptide (and its analogues) could yield new information about neurotransmitter
      release.

PMID- 1359526
TI  - Exogenous modification of nitrovasodilator-induced cyclic GMP formation in human
      lymphocytes.
AB  - The effects of exogenous guanosine 5'-triphosphate (GTP), guanosine 5'-(gamma
      thio)triphosphate (GTP gamma S), cysteine and Trolox C, a water soluble vitamin E
      analogue, were studied on basal and nitrovasodilator-induced cyclic GMP formation
      in isolated human lymphocytes. Incubation of lymphocytes in the presence of GTP
      (0.1 mM) and GTP gamma S (0.1 mM) increased cyclic GMP more than twofold. SIN-1
      and sodium nitroprusside dose-dependently increased cyclic GMP, but nitroglycerin
      and sodium nitrite were ineffective. GTP and GTP gamma S potentiated SIN-1 and
      sodium nitroprusside-induced cyclic GMP formation. In the presence of GTP and GTP
      gamma S, nitroglycerin, but not sodium nitrite, was able to increase lymphocyte
      cyclic GMP. Cysteine (1 mM) enhanced cyclic GMP formation induced by sodium
      nitroprusside and nitroglycerin. Trolox C (0.1 mM) potentiated SIN-1-induced
      cyclic GMP formation. These results indicate that exogenous GTP and GTP gamma S
      enhance guanylate cyclase stimulation by spontaneous nitric oxide releasers and
      nitroglycerin in lymphocytes. Cysteine, a redox-compound and Trolox C, an
      antioxidant, have different effects on guanylate cyclase activation by nitric
      oxide releasers, SIN-1 and sodium nitroprusside.

PMID- 1359527
TI  - Radiographic, haematological, and biochemical findings in a fetus with Caffey
      disease.
AB  - An early case of prenatal Caffey disease is reported. Ultrasound examination
      performed at 20 weeks showed major angulations of long bones, but both ultrasound
      scan and X-rays failed to make the differential diagnosis between Caffey disease
      and lethal osteogenesis imperfecta. A cordocentesis allowed us to find important
      biological abnormalities. The pregnancy was terminated after the rapid
      development of hydrops fetalis. The definitive diagnosis of Caffey disease was
      obtained by special X-ray and pathological study.

PMID- 1359528
TI  - [New dopamine agonists in cardiovascular therapy].
AB  - Dopamine, a naturally occurring catecholamine, has been extensively used in
      intensive care for many years. Dopamine stimulates different types of adrenergic
      receptors: alpha-1 and -2, beta-1 and -2, and dopamine-1 and -2. The renal
      effects of dopamine are the result of dopamine-1 receptor (DA1) stimulation:
      renal vasodilation and natriuresis. DA2-receptor stimulation lowers plasma
      aldosterone and norepinephrine levels. Recently, several new dopamine agonists
      have been developed. Fenoldopam, a selective DA1-agonist, induces renal and
      systemic vasodilation with an increase in renal blood flow. This is accompanied
      by an increase in natriuresis and diuresis. Dopexamine, a DA1- and beta-2
      agonist, is administered intravenously. It is used, like dopamine, in the
      treatment of congestive heart failure. However, the use of dopamine (and
      dopexamine) is limited by its unique intravenous availability. Ibopamine is an
      selective dopamine agonist for oral use. Several clinical studies have
      demonstrated the efficacy of ibopamine in the treatment of patients with
      congestive heart failure and its mild renal effects.

PMID- 1359529
TI  - [Renal oncocytoma in multiple endocrine neoplasia type 1].

PMID- 1359530
TI  - [Proceedings of the 77th Workshop of the Work Group Pathophysiology of
      Respiration. Kurzenberg Oberfranken, 11-12 October 1991. Abstracts].

PMID- 1359531
TI  - Restriction-fragment-length polymorphism and variation in electrophoretic
      karyotype in Naegleria fowleri from Japan.
AB  - Strains of Naegleria fowleri isolated in Japan from two different places were
      found to differ in electrophoretic karyotype and restriction-fragment-length
      polymorphism (RFLP) both from each other and from strains isolated on other
      continents. Using the Wagner parsimony method on the RFLP, we found that the
      Japanese isolates are most closely related to the Australian isolates and most
      distinct from the European isolates.

PMID- 1359532
TI  - Appearance in Europe of Naegleria fowleri displaying the Australian type of
      restriction-fragment-length polymorphism.
AB  - We report for the first time the isolation in Europe of Naegleria fowleri showing
      a type of restriction-fragment-length polymorphism (RFLP) usually found in
      Australia. The presence of this type as well as the European type fluctuated with
      time in the cooling waters of the nuclear power station investigated. Two
      possible explanations for the appearance of the Australian N. fowleri type in
      Europe are presented.

PMID- 1359533
TI  - Isolation and characterization of allelic losses and gains in colorectal tumors
      by arbitrarily primed polymerase chain reaction.
AB  - The arbitrarily primed polymerase chain reaction (AP-PCR) [Welsh, J. &
      McClelland, M. (1990) Nucleic Acids Res. 18, 7213-7218] has been used to detect
      somatic genetic alterations in tumors of the colon and rectum. DNA fingerprints
      generated by single arbitrary primers were compared between normal and tumor
      tissue of the same individuals. AP-PCR bands showing decreased and increased
      intensities in tumor tissue DNA, relative to normal, have been cloned after
      reamplification with the same arbitrary primer. Standard restriction fragment
      length polymorphism and Southern blot analyses show that these DNA sequences have
      undergone allelic losses and gains, respectively, in the tumor cell genome. The
      deleted sequences have been assigned to the short arm of chromosome 17 by PCR of
      somatic hamster/human cell hybrids and linkage analysis. These results show the
      ability of the AP-PCR to detect and isolate, in a single step, DNA sequences
      representing two of the genetic alterations that underlie the aneuploidy of
      cancer cells: losses of heterozygosity and chromosomal gains. Altogether, they
      also show the quantitative nature of the amplification levels obtained in vitro
      by AP-PCR, which thus provides the basis for an alternative molecular approach to
      cancer cytogenetics.

PMID- 1359534
TI  - Cholinergic agonists and interleukin 1 regulate processing and secretion of the
      Alzheimer beta/A4 amyloid protein precursor.
AB  - Activation of protein kinase C by phorbol esters is known to accelerate the
      processing and secretion of the beta/A4 amyloid protein precursor. We have now
      examined various first messengers that increase protein kinase C activity of
      target cells for their ability to affect beta/A4 amyloid protein precursor
      metabolism. Acetylcholine and interleukin 1, which are altered in Alzheimer
      disease, were shown to increase processing of the beta/A4 amyloid protein
      precursor via the secretory cleavage pathway. Cholinergic agonists stimulated
      secretion in human glioma and neuroblastoma cells as well as in PC12 cells
      transfected with the M1 receptor, while interleukin 1 stimulated secretion in
      human endothelial and glioma cells.

PMID- 1359535
TI  - "7-tetrahydrobiopterin," a naturally occurring analogue of tetrahydrobiopterin,
      is a cofactor for and a potential inhibitor of the aromatic amino acid
      hydroxylases.
AB  - The ability of 2-amino-4-hydroxy-7-[dihydroxylpropyl-(L-erythro)-5,6,7,8-tetrahyd
      ropterin] ("7-tetrahydrobiopterin" or 7-BH4) to substitute for the natural
      cofactor tetrahydrobiopterin (BH4) has been studied in vitro in the reactions of
      the three mammalian aromatic amino acid hydroxylases. With rat liver
      phenylalanine hydroxylase, the apparent Km for 7-BH4 is 160 microM, a value that
      is approximately 60-fold greater than that for the natural cofactor. In contrast,
      the hydroxylase reaction is severely inhibited by as little as 1 microM 7-BH4
      when assayed in the presence of physiological concentrations of BH4. This
      inhibition can be overcome either by an increase in the concentration of BH4 or a
      decrease in the concentration of phenylalanine. With both rat brain tryptophan
      hydroxylase and rat pheochromocytoma tyrosine hydroxylase, the Km value for 7-BH4
      is about one order of magnitude greater than the Km for BH4. Accordingly, 7-BH4
      is a poor competitive inhibitor of both tryptophan and tyrosine hydroxylase.
      Thus, our results suggest that the observed hyperphenylalaninemia in patients who
      excrete 7-BH4 in their urine may arise directly from the inhibition of
      phenylalanine hydroxylase by low levels of this pterin. On the other hand, it is
      less likely that low levels of 7-BH4 would affect the activity of tyrosine or
      tryptophan hydroxylase in vivo.

PMID- 1359536
TI  - Coordinated regulation and inositol-mediated and fatty acid-mediated repression
      of fatty acid synthase genes in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, FAS1, FAS2, and FAS3 are the genes involved in
      saturated fatty acid biosynthesis. The enzymatic activities of both fatty acid
      synthase (FAS) and acetyl-CoA carboxylase are reduced 2- to 3-fold when yeast
      cells are grown in the presence of exogenous fatty acids. The mRNA levels of the
      FAS genes are correspondingly lower under repressive conditions. Expression of
      the FAS-lacZ reporter gene is also regulated by fatty acids. When a FAS2
      multicopy plasmid is present in the cells, expression of both FAS1 and FAS3
      increases. Thus, the FAS genes are coordinately regulated. Deletion analyses of
      the regulatory regions of FAS1 and FAS2 revealed common regulatory sequences.
      These include the GGCCAAAAAC and AGCCAAGCA sequences that have a common GCCAA
      core sequence and the UASINO (upstream activation sequence). Derepression of the
      FAS genes in the absence of exogenous inositol is not observed when UASINO is
      mutated, indicating that this cis element is a positive regulator of these genes.
      The GCCAA elements and UASINO act synergistically for optimal expression of the
      FAS genes.

PMID- 1359537
TI  - A role for Quox-8 in the establishment of the dorsoventral pattern during
      vertebrate development.
AB  - We have been interested in the possible involvement of the gene Quox-8, a member
      of the Hox-7/msh family of homeobox-containing genes in the patterning of the
      neural tube and the somitic-derived mesoderm. We demonstrate that in the
      embryonic day 2-6 avian embryo, the expression of Quox-8 in the roof plate
      depends upon (i) the normal dorsoventral orientation of the neural primordium and
      (ii) interactions between the dorsal neural tube and the superficial ectoderm. We
      also show that Quox-8 is expressed in the dorsal mesenchyme located between the
      neural tube and the superficial ectoderm that yields the spinous processes of the
      vertebrae. Experimental inhibition of Quox-8 expression in these areas of the
      dorsal mesenchyme results in the failure of its differentiation into vertebral
      cartilage. We conclude, therefore, that this gene is involved in the patterning
      of vertebral structures through a cascade of tissue interactions primarily
      occurring between the dorsal neural tube and the overlying ectoderm.

PMID- 1359538
TI  - Cooperation of GroEL/GroES and DnaK/DnaJ heat shock proteins in preventing
      protein misfolding in Escherichia coli.
AB  - Newly synthesized proteins aggregate extensively in Escherichia coli rpoH
      mutants, which are deficient in the heat shock proteins (hsp). Overproduction of
      either GroEL and GroES or DnaK and DnaJ prevents aggregation. If expressed
      together, the four hsp are effective at physiological concentrations. Our data
      suggest that the GroEL and GroES proteins and the DnaK and DnaJ proteins have
      complementary functions in the folding and assembly of most proteins.

PMID- 1359539
TI  - Synthetic phosphopeptide immunogens yield activation-specific antibodies to the c
      erbB-2 receptor.
AB  - We inoculated rabbits with synthetic phosphopeptides, duplicating a major
      autophosphorylation site of the c-erbB-2 protooncogene product. The rabbits
      produced antisera that, after reverse immunoaffinity purification, selectively
      recognize the erbB-2 protein in its enzymatically active configuration. These
      anti-phosphopeptide antisera identify a subset of erbB-2-positive human cell
      lines wherein the protein is constitutively active as a tyrosine kinase.
      Synthetic phosphopeptides incorporating informative protein phosphorylation sites
      may prove useful for generating antibodies that indicate the activation state of
      additional tyrosine kinases and perhaps other proteins phosphorylated on serine
      and threonine residues.

PMID- 1359540
TI  - Glutamate receptors of Drosophila melanogaster: cloning of a kainate-selective
      subunit expressed in the central nervous system.
AB  - We report the isolation and functional characterization of cDNAs encoding a
      Drosophila kainate-selective glutamate receptor. The deduced mature 964-residue
      protein (DGluR-I) is 108,482 Da and exhibits significant homology to mammalian
      glutamate receptor subunits. Injection of DGluR-I cRNA into Xenopus oocytes
      generated kainate-operated ion channels which were blocked by the selective non-N
      methyl-D-aspartate receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione and
      philanthotoxin. DGluR-I transcripts are differentially expressed during
      Drosophila development and, in late embryogenesis, accumulate in the central
      nervous system.

PMID- 1359541
TI  - Expression of the neu protooncogene in the mammary epithelium of transgenic mice
      induces metastatic disease.
AB  - Overexpression and amplification of the neu (c-erbB2, ERBB2) protooncogene have
      been implicated in the development of aggressive human breast cancer. To directly
      assess the effect of mammary gland-specific expression of the neu protooncogene,
      transgenic mice carrying unactivated neu under the transcriptional control of the
      mouse mammary tumor virus promoter/enhancer were established. By contrast to the
      rapid tumor progression observed in several transgenic strains carrying the
      activated neu transgene, expression of unactivated neu in the mammary epithelium
      resulted in the development of focal mammary tumors after long latency. The
      majority of the mammary tumors analyzed expressed elevated levels of neu-encoded
      mRNA and protein. Overexpression of neu in the mammary tumors was also associated
      with elevated neu intrinsic tyrosine kinase activity and the de novo tyrosine
      phosphorylation of several cellular proteins. Interestingly, many of the tumor
      bearing transgenic mice developed secondary metastatic tumors in the lung. These
      observations suggest that overexpression of the unactivated neu protein can
      induce metastatic disease after long latency.

PMID- 1359542
TI  - N-methyl-D-aspartate receptor antagonists disrupt the formation of a mammalian
      neural map.
AB  - The topographic ordering of retinal connections in the rat superior colliculus
      emerges during early postnatal life from an initially diffuse projection.
      Disruption of N-methyl-D-aspartate (NMDA) receptor activity in the superior
      colliculus during this period interferes with map remodeling. In rats chronically
      treated with NMDA receptor antagonists during the first two postnatal weeks,
      aberrant axons remain and arborize at topographically incorrect sites. These
      results indicate that, at a stage preceding visually evoked activity, normal NMDA
      receptor function is important for the development of an ordered neural map in
      the mammalian brain.

PMID- 1359543
TI  - Kindred S thyroid hormone receptor is an active and constitutive silencer and a
      repressor for thyroid hormone and retinoic acid responses.
AB  - Mutations in the gene encoding the human thyroid hormone receptor beta (hTR beta)
      have been associated with generalized thyroid hormone resistance (GTHR). However,
      the molecular basis by which the receptor mutants cause the clinical symptoms is
      largely unknown. We show here that the beta form of the human receptor possesses,
      in addition to hormone-dependent activation, the ability to repress basal-level
      activity of a target promoter. This silencing function is localized in the
      carboxyl-terminal part of the receptor and can be transferred to a heterologous
      DNA binding domain. This mode of silencing is therefore distinct from inhibition
      by competition with activator proteins on DNA. We show that two receptor mutants
      isolated from patients with GTHR are impaired in transcriptional activation but
      fully retain the silencing function, which enforces dominant negative regulation
      by the receptor. Interestingly, the kindred S receptor (hTR delta 332) acts as a
      constitutive repressor with a strong silencing ability similar to that of the v
      erbA oncogene product. We also provide evidence for distinct transcriptional
      regulatory properties of both proteins. Finally, we show that both thyroid
      hormone- and retinoic acid-responsive genes are potentially repressed to generate
      the clinical manifestations of the GTHR syndrome. Our findings suggest that
      silencing plays an important role in the phenotypic expression of the symptoms in
      patients with GTHR.

PMID- 1359545
TI  - The dual effect of internal tetramethylammonium ions on the open states of the
      sodium channel in the squid giant axon.
AB  - Voltage-clamp recordings of INa in squid axons dialysed with Cs or TMA, and
      bathed in low Na choline seawater, showed that, except close to threshold, the
      initial peak of fast-inactivating current was invariably decreased by TMA,
      whereas the non-inactivating current in the steady state was simultaneously
      increased. The results suggest that although TMA does not act directly on the
      movements of the voltage sensors that activate the sodium system, it blocks
      single-channel conductance in a voltage-dependent fashion in both the open states
      of the Na channel, while it has an entirely different type of action by
      increasing the probability of late openings in the steady state. Another
      difference between the two open states was that the sodium permeability
      coefficient had a Q10 of 1.8 in the initial open state, whereas in the steady
      state the effect of temperature was much smaller or even negative.

PMID- 1359544
TI  - NMR structure determination reveals that the homeodomain is connected through a
      flexible linker to the main body in the Drosophila Antennapedia protein.
AB  - The secondary structure of an N-terminally elongated Antennapedia (Antp)
      homeodomain (HD) polypeptide containing residues -14 to 67, where residues 1-60
      constitute the HD, has been determined by NMR in solution. This polypeptide
      contains the conserved motif -Tyr-Pro-Trp-Met- (YPWM) at positions -9 to -6.
      Despite the hydrophobic nature of this tetrapeptide motif, the N-terminal arm
      consisting of residues -14 to 6 is flexibly disordered, and the well-defined part
      of the HD structure with residues 7-59 is indistinguishable from that of the
      shorter Antp HD polypeptide (where positions 0, 1, and 67 are methionine,
      arginine, and glycine, respectively). In vitro biochemical studies showed that
      the stability and specificity of the DNA binding previously observed for the
      shorter Antp HD polypeptide is preserved in the elongated polypeptide. These
      results strongly support the view that the HD is connected through a flexible
      linker to the main body in the Antp protein and that the minor groove contacts by
      the N-terminal arm (residues 1-6) in the Antp HD-DNA complex are an intrinsic
      feature of the DNA-binding interactions of the intact Antp protein.

PMID- 1359546
TI  - Testing the role of intraguild predation in regulating hedgehog populations.
AB  - Potential competitors that eat each other can engender patterns of spatial
      segregation similar to those produced by competition, and distinguishable only by
      field manipulation. This paper reports the results of a perturbation experiment
      to test the factors responsible for small-scale discontinuities in the
      distribution of a common insectivore. Populations of hedgehogs (Erinaceus
      europaeus) were monitored following their introductions into an area where they
      had been absent, and into a neighbouring area where they were known to persist.
      The two sites had a similar availability of preferred habitat, and the growth
      rates of introduced hedgehogs were similar. The density of badgers (Meles meles),
      larger members of the same guild, appears to produce differences in mortality and
      dispersal, which returned the populations close to their original levels within 2
      months of the transplant.

PMID- 1359547
TI  - Clonal structure of the introduced freshwater snail Potamopyrgus antipodarum
      (Prosobranchia: Hydrobiidae), as revealed by DNA fingerprinting.
AB  - Multi-locus DNA fingerprints were obtained from individuals of the hydrobiid
      snail, Potamopyrgus antipodarum (= P. jenkinsi), by using an RNA derivative (pSPT
      18.15) of Jeffrey's 33.15 minisatellite core sequence. Whole-body homogenization
      of snails yielded 3.21 +/- 0.09 micrograms DNA per individual, producing complex
      profiles comprising 12-22 fragments within the 1.0-20.0 kilobase (kb) size range.
      Fingerprints from natural and experimental populations identified three distinct
      clonal genotypes corresponding to morphological strains A, B and C, with only
      rare mutational variants. Mother-offspring comparisons of genetic fingerprints
      revealed genetic stability during apomictic parthenogenesis. Data support the
      notion that British populations of P. antipodarum comprise three widespread
      obligate parthenogenetic clones resulting from a mid-19th Century introduction
      from Australasia. The present-day low levels of genotypic diversity are discussed
      in relation to the typical occurrence of P. antipodarum in man-made or immature
      habitats.

PMID- 1359548
TI  - Drosophila projectin: relatedness to titin and twitchin and correlation with
      lethal(4) 102 CDa and bent-dominant mutants.
AB  - We have investigated projectin, a large protein of insect muscles, in Drosophila
      melanogaster. The 5.3 kilobases of coding sequence reported here contains Class I
      and Class II motifs characteristic of titin and twitchin, arranged in a three
      domain ... [II-I-I] [II-I-I] ... pattern. Two mutants mapped to the location of
      the projectin gene in the 102C subdivision of chromosome 4, lethal(4) 102 CDa and
      bent-Dominant, have DNA rearrangements within their projectin gene. The lethal(4)
      102 CDa mutant has a 141 nucleotide insertion containing stop codons in all three
      reading frames within an exon sequence, showing that it cannot synthesize normal
      projectin. Both bent-Dominant and lethal(4) 102 CDa homozygotes die at the
      completion of embryogenesis because they are unable to escape the egg vitelline
      membrane. We propose that this hatching failure is due to muscle weakness caused
      by projectin defects.

PMID- 1359550
TI  - Parallel reflex and central control of promotor and receptor motoneurons in
      crayfish.
AB  - We describe the reflex and central control of an identified motoneuron (rm 1) to
      a crayfish muscle receptor, the thoracocoxal muscle receptor organ (TCMRO), and
      compare it with the in-parallel, 'extrafusal' promotor motorneurons. Rm 1 is
      spontaneously active in an isolated preparation. This activity is modulated in
      phase with centrally driven promoter nerve activity, suggesting coactivation of
      promotor and receptor-motor motoneurons. Rm 1 is autogenetically modulated, in a
      phase-dependent manner, by stretching the TCMRO: during promotor bursts rm 1 is
      excited by dynamic stretch, but during remotor bursts it is inhibited by the same
      stimulus. This effect is mediated by a single, identified TCMRO afferent, the
      dynamically sensitive T-fibre. At or near maximally stretched lengths of the
      TCMRO a tonic inhibition of rm 1 is revealed. This effect is mediated by another
      identified TCMRO afferent, the statistically sensitive S-fibre. The thoracocoxal
      chordotonal organ is a non-muscular receptor spanning the same joint but
      signalling the opposite direction of movement. Dynamic movement stimulation of
      this receptor also excites rm 1, a reflex that could counteract TCMRO slackening.
      These results demonstrate a complex central and reflex control of the TCMRO,
      which could regulate reflex gain throughout the step cycle during walking in the
      intact animal.

PMID- 1359549
TI  - The post-embryonic development of cell properties and synaptic drive underlying
      locomotor rhythm generation in Xenopus larvae.
AB  - In the first 24 h of post-embryonic development, the motor rhythm underlying
      swimming in Xenopus laevis tadpoles changes from brief (ca. 7 ms) ventral root
      discharge in each cycle to bursts of activity lasting around 20 ms (Sillar et al.
      1991). Because individual motoneurons in the spinal cord of newly hatched embryos
      normally fire only a single impulse per cycle, two possible changes underly the
      transition to motor bursts seen in larval ventral roots; desynchronization of
      neurons in a given ventral root which continue to fire once per cycle, or the
      developmental acquisition of a multiple spike capability in individual
      motoneurons. Here we have recorded intracellularly from ventrally positioned
      spinal neurons, presumed to be myotomal motoneurons, in stage 37/38 embryos and
      24 h later in development in stage 42 larvae. We find that (i) larval neurons are
      able to fire more than one impulse per cycle of fictive swimming activity; (ii)
      unlike in the embryo, they generally will fire multiple impulses in response to
      injected depolarizing current; (iii) the synaptic drive to motoneurons during
      swimming increases dramatically in complexity, although it still consists of
      alternating phases of synaptic excitation and chloride-dependent inhibition,
      superimposed upon tonic synaptic depolarization. The results therefore suggest a
      developmental change in the membrane properties of rhythmically active neurons as
      a major factor in the post-embryonic development of swimming in Xenopus larvae.
      This change appears to occur in premotor rhythm generating interneurons as well
      as in the motoneurons themselves and may satisfy a demand for behavioural
      flexibility that allows larvae to survive in a complex and changing environment.

PMID- 1359551
TI  - A slow voltage-activated potassium current in rat vagal neurons.
AB  - Potassium currents play a key role in controlling the excitability of neurons. In
      this paper we describe the properties of a novel voltage-activated potassium
      current in neurons of the rat dorsal motor nucleus of the vagus (DMV).
      Intracellular recordings were made from DMV neurons in transverse slices of the
      medulla. Under voltage clamp, depolarization of these neurons from hyperpolarized
      membrane potentials (more negative than -80 mV) activated two transient outward
      currents. One had fast kinetics and had properties similar to A-currents. The
      other current had an activation threshold of around -95 mV (from a holding
      potential -110 mV) and inactivated with a time constant of about 3s. It had a
      reversal potential close to the potassium equilibrium potential. This current was
      not calcium dependent and was not blocked by 4-aminopyridine (5 mM), catechol (5
      mM) or tetraethylammonium (20 mM). It was completely inactivated at the resting
      membrane potential. This current therefore represents a new type of voltage
      activated potassium current. It is suggested that this current might act as a
      brake to repetitive firing when the neuron is depolarized from membrane
      potentials negative to the resting potential.

PMID- 1359552
TI  - [14C]deoxyglucose labelling of functional activity in the cephalopod central
      nervous system.
AB  - For the first time, the [14C]deoxyglucose radioautographic technique has been
      successfully used to map physiological activity in cephalopod brains. In
      unilaterally blinded octopus and cuttlefish, the optic lobe of the deprived side
      showed a decreased uptake of the labelled tracer. This suggests that the uptake
      is related to functional activity. The potential of the [14C]deoxyglucose
      technique as a powerful tool in studying the functional organization of
      cephalopod brains is discussed.

PMID- 1359554
TI  - Human vision combines oriented filters to compute edges.
AB  - The experiments examined the perceived spatial structure of plaid patterns,
      composed of two or three sinusoidal gratings of the same spatial frequency,
      superimposed at different orientations. Perceived structure corresponded well
      with the pattern of zero crossings in the output of a circular spatial filter
      applied to the image. This lends some support to Marr & Hildreth's (Proc. R. Soc.
      Lond. B 207, 187 (1980)) theory of edge detection as a model for human vision,
      but with a very different implementation. The perceived structure of two
      component plaids was distorted by prior exposure to a masking or adapting
      grating, in a way that was perceptually equivalent to reducing the contrast of
      one of the plaid components. This was confirmed by finding that the plaid
      distortion could be nulled by increasing the contrast of the masked or adapted
      component. A corresponding reduction of perceived contrast for single gratings
      was observed after adaptation and in some masking conditions. I propose the
      outlines of a model for edge finding in human vision. The plaid components are
      processed through cortical, orientation-selective filters that are subject to
      attenuation by forward masking and adaptation. The outputs of these oriented
      filters are then linearly summed to emulate circular filtering, and zero
      crossings (zcs) in the combined output are used to determine edge locations.
      Masking or adapting to a grating attenuates some oriented filters more than
      others, and although this changes only the effective contrast of the components,
      it results in a geometric distortion at the zc level after different filters have
      been combined. The orientation of zcs may not correspond at all with the
      orientation of Fourier components, but they are correctly predicted by this two
      stage model. The oriented filters are not 'orientation detectors', but are
      precursors to a more subtle stage that locates and represents spatial features.

PMID- 1359553
TI  - Heterogeneity of receptor immunoreactivity at synapses of glycine-utilizing
      neurons.
AB  - Neurons often contain, and probably release, more than one neuroactive substance
      that may have diverse or opposite actions on the postsynaptic cell. It remains
      unexplained how these neurons utilize their multiple neuroactive substances while
      maintaining appropriate resolution of neurotransmitter functions. Here, we have
      examined the ultrastructural localization of glycine receptors by using a
      monoclonal antibody directed to the intracellular domain of the strychnine
      sensitive glycine receptor. We have found that glycine receptors are only
      localized to 56% of the synapses made by presumed 'glycinergic' (more accurately,
      glycine-utilizing) amacrine cells in the turtle retina. The remaining synapses
      made by these same boutons show no evidence of glycine receptors. As there is no
      evidence to suggest the presence of a second type of glycine receptor, these data
      indicate that only a portion of the postsynaptic sites contacted by the glycine
      utilizing neurons can respond to glycine. They also suggest that a neuron
      containing multiple neuroactive substances can selectively affect postsynaptic
      elements by means of heterogeneous receptor localization.

PMID- 1359555
TI  - Rigorous analysis of light diffraction by a striated muscle fibre.
AB  - A rigorous theory describing the diffraction of light by a muscle fibre has been
      formulated. The basis of this analysis is the rigorous coupled-wave approach of
      T. K. Gaylord & M. G. Moharam (Proc. IEEE 73, 894 (1985)); however, we obtain
      here a closed-form analytical result that is both mathematically simple and
      physically easy to understand. We have compared our results on striated muscle
      fibres with the analytical results obtained by A. F. Huxley (Proc. R. Soc. Lond.
      B 241, 65 (1990)) using the normal mode approach, and with those obtained by R.
      A. Thornhill, N. Thomas & N. Berovic (Eur. Biophys. J. 20, 87 (1991)) using a
      multiwave first-order coupled-wave approximation. For an equivalent set of
      assigned fibre parameters, our results are consistent with these mentioned.
      Extension of this analysis to a fibre with different structures showed that the
      differences in diffraction efficiencies of different orders for a frog skeletal
      fibre and for an insect flight fibre are clear; the sensitivity to distinct
      structural organization of the fibre is very good.

PMID- 1359556
TI  - Localization of cholinergic and purinergic receptors on outer hair cells isolated
      from the guinea-pig cochlea.
AB  - Acetylcholine (ACh) and adenosine 5'-triphosphate (ATP) are shown to act in
      opposing fashion on guinea-pig cochlear outer hair cells (OHCS) via receptors
      localized within different fluid compartments of the organ of Corti. The
      cholinergic (efferent) receptors localized at the basal (perilymphatic) region of
      these cells activated a rapidly desensitizing hyperpolarizing K+ current. In
      contrast, purinergic (ATP) receptors were localized at the apical (endolymphatic)
      surface of OHCS and activated a depolarizing nonselective cation current which
      exhibited inward rectification and lacked desensitization. Localization of the
      receptors was determined by using whole-cell patch-clamp, by recording onset
      latencies and response amplitudes to pulses of either ACh or ATP pressure-applied
      at selected sites along the length of isolated OHCS. Under voltage-clamp at -60
      mV, the largest ACh-induced (outward) currents were recorded when ACh was
      directed at the basal region of the cells. Conversely, the maximum (inward) ATP
      currents were obtained when ATP was directed toward the apical surface of these
      cells. Onset latencies increased rapidly from a minimum of approximately 10 ms
      for either ACh or ATP as the drug pipette was moved away from these optimal
      sites. The ATP response was antagonized by amiloride in a dose-dependent manner
      with a KD of approximately 400 microM. The localization of P2-type purinoceptors
      to the endolymphatic surface of OHCS suggests that ATP mediates a humoral
      modulation of the mechano-electrical transduction process.

PMID- 1359557
TI  - Detecting gene conversion: primate visual pigment genes.
AB  - The effects of gene conversion can be detected in the DNA sequences of multigene
      families. We develop a permutation test of the significance of patterns of
      sequence mismatches, and apply it to the sequences of the red- and green
      sensitive visual pigment genes of human and the diana monkey. Whereas
      conventional tests of the rate of sequence divergence are equivocal, the
      permutation test convincingly excludes divergence in the absence of gene
      conversion (p = 10(-6)).

PMID- 1359558
TI  - A simple model for the function of proteoglycans and collagen in the response to
      compression of the intervertebral disc.
AB  - The nucleus pulposus of the intervertebral disc exerts a pressure which enables
      it to support axial compression when contained by the annulus fibrosus. The disc
      was modelled as a thick-walled cylindrical pressure vessel in which the nucleus
      was contained radially by the annulus. As a result, the stress in the annulus had
      radial (compressive) as well as tangential (tensile) components. The radial
      stress at a given point in the annulus was considered to be balanced by the
      internal pressure which is expected to arise from the attraction of water by
      proteoglycans. There was a reasonable agreement between the calculated radial
      stress distribution and published results on the distribution of water within the
      annulus. As the internal pressure is expected to be isotropic, the annulus was
      expected to contribute to the axial resistance to compression of the disc; this
      contribution would be equal, in magnitude, to the radial stress. Predictions of
      the pressure distribution within the annulus were similar to published
      experimental measurements made in the radial and axial directions. The tangential
      stress within the annulus was considered to arise from the restoring stress in
      its strained collagen fibrils.

PMID- 1359559
TI  - Progressive loss of semantic memory in a case of Alzheimer's disease.
AB  - The breakdown of semantic memory in a patient with Alzheimer's disease was
      monitored by using a word-picture matching task. Performance deteriorated from a
      time when target pictures were selected virtually without error to a time when
      targets and semantically related distractor pictures were selected equally often.
      From this point, selection deteriorated rapidly to random. Knowledge of category
      membership and semantic features declined together over the same period. No
      consistency in item selection could be discerned, and successful selection in
      early tests was not influenced by either the name frequency or the familiarity of
      the target. The findings are argued to support a theory of access to semantic
      memory which is non-hierarchical.

PMID- 1359560
TI  - Identification of chimpanzee subspecies with DNA from hair and allele-specific
      probes.
AB  - We describe a non-invasive method of determining the subspecies identity of
      common chimpanzees (Pan troglodytes), based on subspecies-specific sequence
      differences in the mitochondrial genome. This procedure involves the extraction
      of DNA from hair, the amplification of a short (410 base pair (b.p.)) segment of
      the non-coding displacement loop (D-loop) by the polymerase chain reaction (PCR),
      and subspecies identification based on rapid allele-specific oligonucleotide
      (ASO) probe dot-blot typing. This approach will contribute to: (i) the colony
      level management of captive chimpanzees by enabling managers to recognize hybrids
      between subspecies and minimize outbreeding depression; (ii) the recognition of
      inappropriately matched individuals in comparative behavioural and experimental
      studies; and (iii) forensic questions surrounding the origin of illegally traded
      animals.

PMID- 1359562
TI  - New Developments in Fatty Acid Oxidation. Proceedings of the 2nd International
      Symposium on Clinical, Biochemical, and Molecular Aspects of Fatty Acid
      Oxidation. Philadelphia, Pennsylvania, November 1991.

PMID- 1359561
TI  - On the block of outward potassium current in rabbit Schwann cells by internal
      sodium ions.
AB  - Currents through delayed rectifier-type K+ channels in Schwann cells cultured
      from rabbit sciatic nerve were studied with patch-clamp techniques. When the
      internal and external solutions contained physiological concentrations of sodium,
      the amplitude of these outward currents declined as the cell was depolarized to
      potentials above about +40 mV, despite the increased driving force. This
      reduction in the amplitude of outward K+ currents was observed in many cells
      before the subtraction of leakage currents; it was also observed for ensemble
      currents recorded in outside-out patches. It was therefore not the result of a
      leak-subtraction artefact nor of inadequate voltage-clamp control. Several lines
      of evidence also suggested that it was not the result of the extracellular
      accumulation of K+. By contrast, when the Na+ ion concentration of the internal
      solution was nominally zero, the reduction in the amplitude of outward K+
      currents at positive membrane potentials was not observed. The apparent amplitude
      of single-channel currents through two types of K+ channel was reduced by 30 mM
      internal Na+, apparently as the result of a rapid 'flickery' block. The results
      suggest that channel block by internal Na+ is largely responsible for the
      negative slope conductance seen in current-voltage plots of whole-cell K+
      currents at positive membrane potentials. In addition, our analysis of single
      channel currents suggests that the current-voltage curve for a delayed rectifier
      channel in rabbit Schwann cells (in the absence of internal Na+) is roughly
      linear with internal and external K+ concentrations of 140 mM and 5.6 mM,
      respectively.

PMID- 1359564
TI  - Prevalence of K329E mutation in the medium-chain acyl-CoA dehydrogenase gene
      determined from Guthrie cards.

PMID- 1359563
TI  - The molecular basis of medium chain acyl-CoA dehydrogenase deficiency: survey and
      evolution of 985A----G transition, and identification of five rare types of
      mutation within the medium chain acyl-CoA dehydrogenase gene.

PMID- 1359565
TI  - Advances in Bone Marrow Purging and Processing. Proceedings of the 3rd
      International Symposium. San Diego, California, October 3-5, 1991.

PMID- 1359566
TI  - Cord blood banking for human hematopoietic cell transplantation.

PMID- 1359567
TI  - Autologous and allogeneic transplantation with peripheral blood stem cells.

PMID- 1359569
TI  - Autologous blood stem cell transplantation for patients with Hodgkin's disease in
      sensitive relapse.

PMID- 1359568
TI  - Peripheral stem cell collection and transplantation in pediatric patients.

PMID- 1359570
TI  - Effects of beta-endorphin on spontaneous uterine contractions. Prostaglandins
      production and 45Ca2+ uptake in uterine strips from ovariectomized rats.
AB  - The effects of beta-endorphin, Met-enkephalin, dynorphin and SKF 10047 on the
      constancy of the isometric developed tension (IDT) of the spontaneous
      contractions of uterine strips isolated from ovariectomized rats were explored.
      beta-endorphin (10(-6) M) was the only opioid that depressed significantly
      uterine constancy of IDT in a concentration dependent fashion. Naloxone, neither
      at 10(-8) M nor at 10(-6) M, altered the negative inotropic influence of beta
      endorphin. Moreover, the basal synthesis and outputs of some prostaglandins
      (PGE1, PGE2 and PGF2 alpha) from rat uteri and the effect of beta-endorphin (10(
      6) M), were determined. It was found that the basal synthesis and release of PGs
      in uteri were significantly inhibited by this endogenous opioid. The effects of
      beta-endorphin (10(-8), 10(-6) and 10(-5) M) on the basal; and oxytocin or
      A23187, induced 45Ca2+ uptake, as well as the influence of naloxone were also
      studied. beta-endorphin at three of the concentrations tested decreased basal
      uterine 45Ca2+ uptake and this action was not prevented by naloxone (10(-8) M).
      The presence of oxytocin and of A23187 augmented significantly 45Ca2+ uptake, an
      effect that was antagonized by beta-endorphin (10(-6) M). The possible role of
      beta-endorphin in uterine functioning via the modulation of uterine PG synthesis
      and Ca2+ uptake is discussed.

PMID- 1359572
TI  - Pipradrol conditioned place preference is blocked by SCH23390.
AB  - We investigated the effect of the selective D1 dopamine antagonist, SCH23390, on
      the establishment of a pipradrol-conditioned place preference (CPP). Among
      various doses of pipradrol (6.25-75.0 mg/kg, SC), a CPP was established at 25.0
      mg/kg. SCH23390 (0.16 mg/kg, IP) blocked the establishment of a CPP by this dose
      of pipradrol. The results suggest that pipradrol produces a rewarding effect and
      that this effect may involve activation of D1 dopamine receptors.

PMID- 1359571
TI  - Evaluation of a stable CCK agonist (A68552) in conditioned avoidance responding
      in mice, rats, and primates: comparison with typical and atypical antipsychotics.
AB  - In a variety of in vivo and in vitro tests, cholecystokinin (CCK) has been shown
      to produce effects that would suggest a functional antagonism of dopamine. On
      that basis, it has been hypothesized that CCK could have antipsychotic effects.
      We compared the CCK agonist, A68552, to the antipsychotics haloperidol (HAL),
      clozapine (CLOZ) and sulpiride (SULP) in various forms of conditioned avoidance
      using rats, mice, and cynomolgus monkeys. In rats, HAL disrupted both acquisition
      of a conditioned shelf-jump avoidance response and performance of the response by
      previously trained animals. CLOZ and SULP were ineffective in suppressing
      performance by previously trained rats but blocked acquisition of the response.
      CLOZ disrupted avoidance responding on the first 3 of 4 consecutive days of
      acquisition. SULP significantly suppressed avoidance responding on the last 3
      days and significantly increased escape failures on day 2. A68552 administered
      during acquisition failed to significantly suppress avoidance responding. In
      mice, both HAL and CLOZ blocked performance of two-way shuttle conditioned
      avoidance at doses (0.1 and 3.0 mg/kg, IP, respectively) that had no effect on
      escape responding. A68552 at doses up to 1.07 mg/kg IP had no effect on
      performance. Mice treated with A68552 during acquisition showed a mild but
      statistically significant suppression of avoidance and an equivalent suppression
      of escape responding. Cynomolgus monkeys trained in a conditioned avoidance
      procedure were sensitive to the disruptive effects of HAL at a dose of 0.03 mg/kg
      IM while A68552 was without significant effect at doses up to those producing
      emesis (0.214 mg/kg, IM). A68552 does not resemble either HAL or the "atypical"
      antipsychotics, CLOZ or SULP, in conditioned avoidance tests.

PMID- 1359573
TI  - Serotonin 5-HT1A receptor-mediated hypothermia in mice: absence of spare
      receptors and rapid induction of tolerance.
AB  - The mixed 5-hydroxytryptamine1A (5-HT1A) receptor agonist/antagonist 8-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol-[4.5]- decane-7,9-dione (BMY
      7378) (5 mg/kg) did not significantly depress body temperature, but pretreatment
      with BMY 7378 blocked hypothermia induced by the selective 5-HT1A agonist 8
      hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In contrast, another partial 5
      HT1A agonist, pindolol (10 mg/kg), slightly but significantly depressed body
      temperature by itself but did not attenuate hypothermia elicited by 8-OH-DPAT.
      Attempts to identify the synaptic locus of the receptor were unsuccessful because
      depletion of central serotonin (5-HT) by treatment with para-chlorophenylalanine
      (PCPA; 3 x 150 mg/kg) did not alter the hypothermic response to 8-OH-DPAT.
      Partial, irreversible 5-HT1A receptor inactivation by N-ethoxycarbonyl-2-ethoxy
      1,2-dihydroquinoline (EEDQ) (1 mg/kg) reduced the maximal hypothermic effect of 8
      OH-DPAT (to 53% of control) without altering its ED50 (0.96 mg/kg). Analysis of
      the data indicated a linear relationship between 5-HT1A receptor occupancy and
      hypothermic response, that is, absence of receptor reserve. When groups of mice
      were treated with each of five different doses of 8-OH-DPAT (0.04, 0.16, 0.63,
      2.5, and 10 mg/kg) 48 h apart, there was a significant reduction in hypothermic
      response after the second injection, but only at the three highest doses. The
      results demonstrate that 8-OH-DPAT-induced hypothermia in mice is mediated by a 5
      HT1A receptor whose synaptic localization is uncertain but that has no receptor
      reserve. In addition, tolerance is observed after only a single agonist
      treatment.

PMID- 1359574
TI  - Benzodiazepine receptor binding of benzodiazepine hypnotics: receptor and ligand
      specificity.
AB  - Benzodiazepine (BDZ) hypnotics bind at a specific receptor located on
      postsynaptic neurons. Some data support specificity of binding for several
      hypnotics to receptor subtypes. We evaluated BDZ receptor binding in cerebral
      cortical membranes using agonist, antagonist, and subtype-specific ligands for
      commonly used hypnotics and their metabolites. All hypnotics competed similarly
      at BDZ1 and BDZ2 receptor subtypes except quazepam and its metabolite 2-oxo
      quazepam and to a lesser extent hydroxyethyl flurazepam (EtOH) flurazepam. These
      compounds had relative specificity for the BDZ1 site. Triazolam, estazolam, and
      flurazepam bound equally to sites labeled by agonists and antagonists but
      desalkylflurazepam, EtOH flurazepam, temazepam, quazepam, and 2-oxo-quazepam did
      not; in addition, these four compounds did not bind to the "peripheral" BDZ site
      labeled by Ro 5-4864. BDZ hypnotics differ in their receptor subtype and ligand
      binding characteristics.

PMID- 1359575
TI  - Parkinson's disease-like effects of S-adenosyl-L-methionine: effects of L-dopa.
AB  - The major symptoms of Parkinson's disease (PD) are due to degeneration of the
      nigrostriatal pathway and depletion of dopamine (DA). Tyrosine hydroxylase (TH),
      norepinephrine (NE), serotonin (5-HT), and melanin pigments are also decreased
      and acetylcholinergic activity increased. Biochemically, increased methylation
      can cause the depletion of DA, NE, 5-HT, and melanin pigments and also an
      increase of acetylcholine; thus, increased methylation can present a biochemical
      picture that resembles the biochemical changes that occur in PD. During the
      therapy of PD with L-dopa, it is well known that L-dopa reacts avidly with S
      adenosyl-L-methionine (SAM), the biologic methyl donor, to produce 3-O-methyl
      dopa. Correspondingly, L-dopa has been shown to deplete the concentration of SAM,
      and SAM has been found to induce PD-like motor impairments in rodents; therefore,
      an excess of SAM-dependent methylation may be associated with Parkinsonism. To
      further study the effects of methylation, SAM was injected into the lateral
      ventricle of rats. SAM caused tremors, rigidity, abnormal posture, and dose
      related hypokinesia. Doses of 9.38, 50, and 400 nM/rat caused 61.9, 73.4, and
      94.8% reduction, respectively, of motor activity. A 200-mg/kg IP dose of L-dopa,
      given before 50 nM SAM, blocked the SAM-induced hypokinesia. SAM also caused a
      decrease in TH immunoreactivity, apparent degeneration of TH-containing fibers,
      loss of neurons, and the accumulation of phagocytic cells in the substantia
      nigra. These results showed that excess SAM in the brain, probably due to its
      ability to increase methylation, can induce symptoms that resemble some of the
      changes that occur in PD.

PMID- 1359576
TI  - Interaction of GABA and serotonin in the anxiolytic action of diazepam and
      serotonergic anxiolytics.
AB  - The general purpose of the present study was to analyze the possible interactions
      between the GABA-benzodiazepine and the serotonergic (5-HT) systems in the
      anxiolytic action of diazepam and the 5-HT1A agonists, ipsapirone, indorenate,
      and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The effect of the
      benzodiazepine receptor antagonist, flumazenil (10.0 mg/kg), on the anxiolytic
      action of ipsapirone (5.0 mg/kg), indorenate (5.0 mg/kg), and 8-OH-DPAT (0.125
      mg/kg) was examined on the avoidance exploratory behavior paradigm in mice. The
      effect of the 5-HT1 blockers, methiotepin (0.31 mg/kg), pindolol (3.1 mg/kg), and
      alprenolol (5.0 mg/kg), on the anxiolytic action of diazepam (0.5 mg/kg) was also
      studied. In the last part of this work, the putative potentiation between
      diazepam (0.25 mg/kg) and each of the serotonergic anxiolytics was investigated.
      The antianxiety effect of diazepam, ipsapirone, indorenate, and 8-OH-DPAT was
      prevented by flumazenil. The serotonergic/beta-blocker, alprenolol, partially
      antagonized the diazepam effect. Finally, a potentiation of suboptimal doses of
      diazepam and ipsapirone, but not with indorenate or 8-OH-DPAT, was observed. The
      findings suggest an interaction between both systems on the anxiolytic action of
      diazepam and the 5-HT1A agonists.

PMID- 1359577
TI  - Anxiolytic-like effects of the noncompetitive NMDA antagonist MK 801.
AB  - The present study examined the effects of the noncompetitive NMDA antagonist, MK
      801 (dizocilpine), on behavior in the conditioned suppression of drinking (CSD)
      punished drinking paradigm, a repeated-measures conflict task. In daily 10- or 15
      min sessions, water-restricted rats drank from a tube that was occasionally
      electrified (0.25- or 0.5-mA shocks signaled by a tone). Trained subjects (4
      weeks of CSD testing) exhibited stable baselines for both punished (approximately
      40 or 100 shocks received/session at the 0.5- and 0.25-mA shock intensities,
      respectively) and unpunished (approximately 15 ml/session water intake at either
      shock intensity) responding. Over a wide range of doses, (+) MK 801 did not
      increase punished responding when administered using a 10-min, 4-h, or 48-h
      pretreatment. However, at a 24-h pretreatment (+) MK 801 (0.04-0.4 mg/kg, IP)
      produced a dramatic and dose-dependent increase in punished responding. The
      "inactive" (-) isomer of MK 801 did not produce a significant anxiolytic-like
      effect in the CSD paradigm at doses up to 2 mg/kg when tested using a 24-h
      pretreatment. These data suggest that the anticonvulsant agent (+) MK 801 also
      may exert antianxiety effects in humans.

PMID- 1359578
TI  - Morphine and naloxone act similarly on glutamate-caused guinea pig ileum
      contraction.
AB  - Both morphine (M) and naloxone (NL) have been reported to have NMDA receptor
      blocking effects, regarded as the reason of opiate physical dependence
      development. On the other hand, glutamate (GLU) has been known to induce the
      contraction of isolated guinea pig ileum via acetylcholine release. Therefore,
      different concentrations of M or NL were investigated on the 1 mM GLU-induced
      contraction of isolated guinea pig ileum fixed at a resting tension of 1 g in
      isolated organ bath. The mean value (359.3 +/- 20 mg) of the GLU-elicited
      contraction force was significantly reduced (318.4 +/- 19.4) by 25 nM M
      concentration in the medium. Consequently, 500 and 750 nM M caused further
      decreases in a rather dose-dependent manner (270.8 +/- 17.4 and 167.8 +/- 16.5
      mg, respectively). One micromolar M contraction nearly abolished (8.0 +/- 8.2 mg)
      the GLU-induced contraction. A similar effect was obtained with the naloxone
      concentrations of 10, 20, 40, and 50 microM. In addition, NL has been shown to
      elicit the contraction of the isolated M-dependent guinea pig ileum. In the
      present study, 20- and 30-microM NL concentrations in the bathing medium caused
      the contraction of the ileum made M-dependent by preincubation with M (333.0 +/-
      32.4 and 309.5 +/- 17.7 mg, respectively). These contraction forces were
      significantly reduced when the NL concentration was increased to 40 microM. And,
      50 microM NL concentration not only failed to induce contraction but caused a
      relaxation (-10.6 +/- 2.3) as well. The results were considered supporting
      evidence for the fact that both M and NL are NMDA receptor blockers.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1359581
TI  - Discriminative stimulus properties of RU 33965, a benzodiazepine receptor weak
      partial inverse agonist.
AB  - Rats were trained to discriminate the low-efficacy benzodiazepine receptor
      inverse agonist RU 33965 from vehicle in a two-lever discrimination task on a
      fixed ratio (FR) 20 schedule. Consistent discrimination was obtained at 0.5 mg/kg
      PO RU 33965. Both leptazol and stronger inverse agonists (FG7142, S-135, RU
      34000) substituted for the cue. The weak inverse agonists/antagonists RU 33094,
      RU 34030, Ro 15-1788, and ZK 93426 also substituted for the cue with the latter
      two compounds being particularly potent. The agonist and partial agonists
      diazepam, RU 33203, and RU 39419 did not substitute for the RU 33965 cue but RU
      39419 antagonised it. The full agonists diazepam and loprazolam only consistently
      antagonised the cue when given IP 5 min pretest. These data suggest that the RU
      33965 cue results from its weak inverse agonist activity at benzodiazepine
      receptors, but kinetic factors must be considered when interpreting drug effects
      in discrimination studies.

PMID- 1359579
TI  - Role of the central serotonergic system in the anticonflict effect of d-AP159.
AB  - d-AP159 is a d-optical isomer, and in rats it has a high affinity for 5
      hydroxytryptamine1A (5-HT1A) receptors and potent anticonflict activity, equal to
      that of buspirone. The anticonflict effects of d-AP159 and buspirone were
      investigated in animals in which lesions of the serotonergic neurons were caused
      by intradorsal raphe (d-RA) injection of the neurotoxin 5,7-dihydroxytryptamine
      (5,7-DHT). The anticonflict effect of buspirone, but not that of d-AP159, was
      attenuated in 5-HT neuron-lesioned rats. The anticonflict effect of d-AP159
      injected into various brain sites was also studied. d-AP159 and buspirone
      microinjected into the d-RA caused significant anticonflict activity in rats.
      There was a significant anticonflict effect of d-AP159 injected into the amygdala
      centralis (ACE), but not the dorsal hippocampus (d-HC). The anticonflict effect
      of d-AP159 injected into the d-RA was antagonized by systemic administration of (
      )propranolol but not Ro 15-1788. This effect of d-AP159 injected into the ACE was
      antagonized by systematic administration of Ro 15-1788 but not (-)propranolol.
      These results suggest that the d-RA and the ACE play important roles in the
      anticonflict effects of d-AP159 but that the mechanisms by which this drug acts
      at these sites are different.

PMID- 1359580
TI  - Vigabatrin has an anxiolytic effect in the elevated plus-maze test of anxiety.
AB  - tau-Vinyl GABA (vigabatrin, GVG) is a novel antiepileptic drug that irreversibly
      inhibits GABA transaminase and elevates GABA levels in all parts of the brain. In
      the present study, we investigated the anxiolytic and behavioral effects of GVG
      in the elevated plus-maze and the hole board compared to diazepam. Doses of 500
      and 1,000 mg/kg GVG were injected IP to different groups of male Wistar rats and
      animals were tested either 4 or 24 h after injection. Animals administered
      diazepam (1.5 mg/kg, IP) and saline (1 ml) were tested 20 min after injection.
      GVG and diazepam were found to decrease significantly the number of squares
      visited and rearing; both had a suppressant effect on locomotor activity. Neither
      drug had an effect on exploration (head dipping). GVG at a dose of 1,000 mg/kg
      was shown to have a similar anxiolytic activity either after 4 or 24 h as
      diazepam, while GVG at 500 mg/kg did not show any significant anxiolytic effect.

PMID- 1359582
TI  - Inhibition of catecholamine synthesis depresses behavior of rats in the holeboard
      and forced swim tests: influence of previous chronic stress.
AB  - Catecholaminergic pathways in the brain are activated during stress and are
      presumably involved in the control of physiological and behavioral changes
      triggered by stress. When repeatedly stressed, adaptive changes have been
      observed in catecholaminergic activity in the brain. In the present experiment,
      it was assessed whether or not chronic exposure to immobilization (IMO) altered
      the influence of catecholamines on behavior in the holeboard and forced swim test
      by administering alpha-methyl-p-tyrosine (an inhibitor of catecholamine
      synthesis). Adult Sprague-Dawley rats were used. Chronic stress amortiguated the
      inhibitory effect of acute IMO on some but not all behaviors in the two tests.
      Whereas previous chronic IMO exacerbated the effects of the drug on struggling
      and immobility in the forced swim test, no change in response to the drug as a
      consequence of chronic IMO was observed in the holeboard test. The present data
      suggest that chronic IMO-induced changes in the catecholaminergic control of some
      behaviors might be related to depression-like states in rats. The actual
      physiological meaning of these changes and the specific receptors involved remain
      to be elucidated.

PMID- 1359583
TI  - Extensive gastrointestinal metabolic conversion limits the oral bioavailability
      of the dopamine D2 agonist N-0923 in freely moving rats.
AB  - The absorption of the dopamine D2 agonist S(-)-2-(N-propyl-N-2-thienylethylamino)
      5-hydroxy-tetralin hydrochloride (1; N-0923) was studied in fasted and non-fasted
      male Albino Wistar rats after intragastric administration of 10.0 mumol.kg-1.
      Blood samples up to 120 min were obtained from the portal vein and the levels of
      1 were monitored with a sensitive HPLC method. The maximal fraction of the drug
      reaching the liver invariable was less than 1% of the dose. Maximal plasma levels
      of 30 pmol.ml-1 were found within 12 min after dosing in fasted animals. Plasma
      concentrations of 1 were measurable up to 60 min, after which they were below the
      quantitation limit of the assay (10 pmol.ml-1). This did not allow detailed
      kinetic analysis. Analysis of the portal blood samples obtained after an oral
      dosing of 10.0 mumol.kg(-1)1 spiked with 0.37 MBq tritium labelled drug showed
      that the amount of unchanged drug which reaches the liver invariably was
      comparable with the concentrations found in the study without radioactivity. In
      vitro incubation of 1 with gastric juice and gut contents showed no degradation.
      Therefore, it can be concluded that 1 undergoes an extensive metabolism in the
      gastrointestinal mucosa.

PMID- 1359584
TI  - 5-Hydroxytryptamine receptors.

PMID- 1359585
TI  - Partial hindrance by beta-adrenoceptors of the antagonism of prazosin against
      adrenoceptor agonists in rat caecum.
AB  - The relaxation of the carbachol-contracted rat isolated caecum by noradrenaline
      (NA), adrenaline (A) and isoproterenol (I) was investigated, to identify the
      pharmacological receptors involved. The organs were pretreated with cocaine to
      block neuronal uptake. The relative potencies of the three agonists were I >> A >
      or = NA, indicating the presence of beta-adrenoceptors. However, the shift of
      concentration-response curves by the beta-adrenoceptor antagonist propranolol
      varied according to the agonist used, suggesting the presence of distorting
      factors. Initial attempts to verify if alpha-adrenoceptors were involved, by
      using the alpha-adrenoceptor antagonist prazosin, were unsuccessful, since the
      shifts of the concentration-response curves were small and were not concentration
      dependent, leading to Schild lines with slopes significantly lower than unity.
      When the experiments with prazosin were repeated in the presence of large
      concentration of propranolol (10(-5) mol/l) to block beta-adrenoceptors, the
      relative potencies were changed to NA > A > or = I, reflecting the presence of
      alpha-adrenoceptors. In addition, the shifts induced by prazosin against A lead
      to Schild lines with slopes not different from 1.0. It is concluded that alpha
      adrenoceptors are also present in the caecum, but its presence can only be
      clearly disclosed after blockade of beta-adrenoceptors. The results are discussed
      in relation to other situations known to hinder the determination of relative
      potencies and competitive antagonism, as for instance the removal of agonist from
      the vicinity of receptors by drug uptake mechanisms.

PMID- 1359586
TI  - A neural network model of the vestibulo-ocular reflex using a local synaptic
      learning rule.
AB  - Vertebrates use the vestibulo-ocular reflex to maintain clear vision during head
      movements. This reflex requires eye-velocity commands from the semicircular
      canals to be integrated (mathematically) to produce eye-position commands for the
      extraocular muscles. This is accomplished by a neural network in the caudal pons.
      A model of this network is proposed using positive feedback via lateral
      inhibition. The model has been adapted to a learning network. We have developed a
      synaptic learning rule using only local information to make the model more
      physiological.

PMID- 1359587
TI  - Hand-eye coordination during sequential tasks.
AB  - The small angle subtended by the human fovea places a premium on the ability to
      quickly and accurately direct the gaze to targets of interest. Thus the resultant
      saccadic eye fixations are a very instructive behaviour, revealing much about the
      underlying cognitive mechanisms that guide them. Of particular interest are the
      eye fixations used in hand-eye coordination. Such coordination has been
      extensively studied for single movements from a source location to a target
      location. In contrast, we have studied multiple fixations where the sources and
      targets are a function of a task and chosen dynamically by the subject according
      to task requirements. The task chosen is a copying task: subjects must copy a
      figure made up of contiguous coloured blocks as fast as possible. The main
      observation is that although eye fixations are used for the terminal phase of
      hand movements, they are used for other tasks before and after that phase. The
      analysis of the spatial and temporal details of these fixations suggests that the
      underlying decision process that moves the eyes leaves key decisions until just
      before they are required.

PMID- 1359588
TI  - Low-level aspects of segmentation and recognition.
AB  - This paper discusses two problems related to three-dimensional object
      recognition. The first is segmentation and the selection of a candidate object in
      the image, the second is the recognition of a three-dimensional object from
      different viewing positions. Regarding segmentation, it is shown how globally
      salient structures can be extracted from a contour image based on geometrical
      attributes, including smoothness and contour length. This computation is
      performed by a parallel network of locally connected neuron-like elements. With
      respect to the effect of viewing, it is shown how the problem can be overcome by
      using the linear combinations of a small number of two-dimensional object views.
      In both problems the emphasis is on methods that are relatively low level in
      nature. Segmentation is performed using a bottom-up process, driven by the
      geometry of image contours. Recognition is performed without using explicit three
      dimensional models, but by the direct manipulation of two-dimensional images.

PMID- 1359589
TI  - The structure and mechanical design of rhinoceros dermal armour.
AB  - The collagenous dermis of the white rhinoceros forms a thick, protective armour
      that is highly specialized in its structure and material properties compared with
      other mammalian skin. Rhinoceros skin is three times thicker than predicted
      allometrically, and it contains a dense and highly ordered three-dimensional
      array of relatively straight and highly crosslinked collagen fibres. The skin of
      the back and flanks exhibits a steep stress-strain curve with very little 'toe'
      region, a high elastic modulus (240 MPa), a high tensile strength (30 MPa), a low
      breaking strain (0.24) and high breaking energy (3 MJm-3) and work of fracture
      (78 kJm-2). By comparison, the belly skin is somewhat less stiff, weaker, and
      more extensible. In compression, rhinoceros skin withstands average stresses and
      strains of 170 MPa and 0.7, respectively, before yielding. As a biological
      material, rhinoceros dorsolateral skin has properties that are intermediate
      between those of 'normal' mammalian skin and tendons. This study shows that the
      dermal armour of the rhinoceros is very well adapted to resist blows from the
      horns of conspecifics, as might occur during aggressive behaviour, due to
      specialized material properties as well as its great thickness.

PMID- 1359590
TI  - Computational aspects of motion perception in natural and artificial vision
      systems.
AB  - In this paper a computational scheme for motion perception in artificial and
      natural vision systems is described. The scheme is motivated by a mathematical
      analysis in which first-order spatial properties of optical flow, such as
      singular points and elementary components of optical flow, are shown to be
      salient features for the computation and analysis of visual motion. The fact that
      different methods for the computation of optical flow produce similar results is
      explained in terms of the simple spatial structure of the image motion of rigid
      bodies. Singular points and elementary flow components are used to compute motion
      parameters, such as time-to-collision and angular velocity, and also to segment
      the visual field into areas which correspond to different motions. Then a number
      of biological implications are discussed. Electrophysiological findings suggest
      that the brain perceives visual motion by detecting and analysing optical flow
      components. However, the cortical neurons, which seem to detect elementary flow
      components, are not able to extract these components from more complex flows. A
      simple model for the organization of the receptive field of these cells, which is
      consistent with anatomical and electrophysiological data, is described at the end
      of the paper.

PMID- 1359591
TI  - Activation, inactivation and recovery in the sodium channels of the squid giant
      axon dialysed with different solutions.
AB  - Comparisons were made between families of ion currents recorded in voltage
      clamped squid axons dialysed with 20 mM NaF and 330 mM CsF or TMAF, and bathed in
      a solution in which four fifths of the Na was replaced by Tris. The permeability
      coefficient PNa,fast for the fast-inactivating current in the initial open state
      was calculated as a function of test potential from the size of the initial peak
      of INa. The permeability coefficient PNa,non for the non-inactivating open state
      was calculated from the steady-state INa that persisted until the end of the test
      pulse. Dialysis with TMA had no direct effect on the QV curve for gating charge.
      The reversal potential for INa,non was always lower than that for INa,fast, the
      mean difference being about -9 mV when dialysing with Cs, but only about -1 mV
      with TMA. Except close to threshold, PNa,fast was roughly halved by dialysis with
      TMA as compared with Cs, but PNa,non was substantially increased. The time
      constant tau h inactivation of the sodium system was slightly increased during
      dialysis with TMA in place of Cs, and there were small shifts in the steady-state
      inactivation curve, but the rate of recovery from inactivation was not measurably
      altered. The flattening off of the tau h curve at increasingly positive test
      potentials corresponded to a steady reduction of the apparent inactivation charge
      until a value of about 0.2e was reached for pulses to 100 mV. The instantaneous I
      V relationship in the steady state was also investigated. The results have a
      useful bearing on the effects of dialysis with TMA, on the differences between
      the initial and steady open states of the sodium channel, and on the relative
      voltage-dependences of the transitions in each direction between the resting and
      inactivated states.

PMID- 1359592
TI  - [Visuo-postural control of schizophrenics--variations of sway area during
      horizontal eye movement].
AB  - In the present study, we investigated the neurological mechanism of commonly
      known specific or unnatural postures in schizophrenic patients. Using a
      gravimeter, body sway studied in 26 chronic schizophrenic patients, 10
      schizoaffective disorder patients and 21 normal subjects. During eye fixation at
      a target while keeping an upright posture, schizophrenic patients presented a
      larger gravimetric area than the normal subjects and the patients with
      schizoaffective disorder. There was a negative correlation (r = -0.509) between
      the standard deviation of the sway gravimetric area during fixation and the dose
      of neuroleptics in schizophrenic patients, but no correlation was found in
      patients with schizoaffective disorder (r = -0.01), although they took
      neuroleptics in a similar regimen to that for the schizophrenics. There was no
      correlation between the standard deviation of the sway gravimetric area during
      fixation and the duration of illness. There was also no correlation between the
      former and the amplitude ratio of saccades during smooth pursuit eye movements.
      When horizontal eye movements pursuing the target were loaded in this experiment,
      both the normal subjects and the patients with schizoaffective disorder showed a
      decrease in a loaded gravimetric area and a tendency towards postural
      stabilization. However, schizophrenic patients having higher SANS scores
      (Andreasen) presented an increase in gravimetric area. This suggests that
      schizophrenic patients with higher SANS score may have organic cerebellar changes
      related to impairment of the mechanism of visual and postural coordinations.

PMID- 1359593
TI  - CSF corticotropin releasing hormone, somatostatin, and thyrotropin releasing
      hormone in schizophrenia.
AB  - Cerebrospinal fluid (CSF) corticotropin releasing hormone (CRH), somatostatin
      (SRIF), and thyrotropin releasing hormone (TRH) were measured by specific
      radioimmunoassay methods in 86 patients who met DSM-III-R criteria for
      schizophrenia or schizophreniform disorder and in 30 neurologic controls. The
      multivariate CSF peptide concentration was significantly different in patients
      compared with controls, but none of the individual variable differences reached
      statistical significance when analyzed separately. There were no significant CSF
      neuropeptide differences among patients with various schizophrenic subtypes.
      Neither global severity of illness nor individual symptoms were correlated with
      CSF neuropeptide concentrations. Although schizophrenic patients showed a pattern
      of mildly lower SRIF and TRH levels in their CSF, together with a weak tendency
      for higher CSF CRH values, these peptide changes did not appear to be
      specifically related to the core features of schizophrenia.

PMID- 1359594
TI  - Dopaminergic responsivity during cocaine abstinence: a pilot study.
AB  - This preliminary study investigated dopamine (DA) function in six hospitalized
      cocaine-dependent subjects (DSM-III-R) who received 1.5 mg/kg of active cocaine
      by mouth, t.i.d., for 3 days followed by 9 days of placebo cocaine. During early
      and late abstinence from cocaine, plasma growth hormone (GH), homovanillic acid
      (HVA), prolactin, and 3-methoxy-4-hydroxyphenethyleneglycol responses to the
      placebo-controlled administration of oral L-dopa 250 mg/carbidopa 25 mg (Sinemet)
      were measured. Sinemet caused significantly greater placebo-corrected increases
      in GH and HVA during early as compared with late abstinence. Acute abstinence
      from cocaine may be associated with increased DA responsivity, which normalizes
      over time.

PMID- 1359595
TI  - Neuropsychological predictors of skills training for chronic psychiatric
      patients.
AB  - Measures of neuropsychological functioning were examined for their relationship
      to skills training ability. In a longitudinal design, 16 psychotic inpatients
      were followed during their involvement in a skills training program. The two
      training programs (Symptom Management and Medication Management) included daily 2
      hour sessions over an 8-month period. Five clinical neuropsychological measures
      and three laboratory-based information processing measures were administered at
      baseline. The outcome variables included two measures of skill knowledge/ability
      and a measure of on-task behavior. Modest correlations were found between outcome
      measures and three types of predictors: serial verbal learning, susceptibility to
      distraction, and vigilance. These findings suggest that selected measures of
      neuropsychological functioning may help to target those cognitive abilities
      necessary for skill acquisition, and may aid in selecting patients most likely to
      benefit from skills training.

PMID- 1359596
TI  - Platelet membrane alpha 2-adrenergic receptors in depression.
AB  - The platelet membrane was used as a model system to examine alpha 2-adrenergic
      receptors in 30 depressed patients and 30 healthy control subjects. The number of
      binding sites and their affinity for 3H-UK 14304 (5-bromo-6-(2-imidazoline-2
      ylamino)-quinoxaline), a potent, highly selective alpha 2-adrenergic receptor
      agonist, was measured. Plasma magnesium and free 3-methoxy-4-hydroxyphenylglycol
      (MHPG) concentrations were assayed in the same sample. A decreased agonist
      receptor affinity was found in depressed patients, whereas receptor density was
      not significantly altered compared with that in control subjects. In bipolar
      depressed and dysthymic patients, there was a tendency toward a higher density of
      alpha 2-adrenergic receptors. This trend was not apparent in unipolar, recurrent
      depressed subjects. Moreover, a positive correlation between Bmax and Kd values
      was observed in patients but not in control subjects--a finding that suggests
      that a compensatory phenomenon occurs in depression. After the patients were
      treated with antidepressant drugs, an increased affinity (decrease in Kd) was
      observed, together with a decrease in binding sites. Plasma magnesium
      concentrations were higher in drug-free depressed patients than in control
      subjects. In addition, magnesium concentrations were negatively correlated with
      the density of alpha 2-adrenergic receptor binding sites in depressed patients,
      both before and during treatment. Lastly, a trend toward a negative correlation
      between plasma MHPG concentration and the number of binding sites was also
      observed. These results suggest a complex multifactorial regulation of alpha 2
      adrenergic receptors, which are probably hyposensitive in depressive syndromes.

PMID- 1359597
TI  - Urinary amines in adults with Tourette's syndrome.
AB  - Urinary amines and their metabolites were examined in 32 adults who met DSM-III-R
      diagnostic criteria for Tourette's Syndrome. These patients were compared with a
      control group that was of similar age and sexual representation. Analyses
      revealed significantly lower levels of 3-methoxy-4-hydroxyphenylglycol and
      serotonin as well as the metabolites of several "trace" amines including
      indoleacetic acid and m- and p-hydroxyphenylacetic acid. These findings persisted
      when Tourette's Syndrome patients taking medications were eliminated from the
      analyses. These data are consistent with reports of neurotransmitter
      abnormalities in children with Tourette's Syndrome. The differences in several
      trace amine metabolites suggest that the pathophysiology in this disorder is
      complex and involves a number of neurotransmitter and neuromodulator systems.

PMID- 1359598
TI  - Effects of intravenous and oral dexamethasone on selected lymphocyte
      subpopulations in normal subjects.
AB  - Our studies describe the effects of 1 mg oral (PO) and intravenous (IV)
      administration of dexamethasone (DEX) on certain subpopulations of circulating
      lymphocytes in normal subjects. We compared the outcomes of PO and IV DEX
      administration because of individual differences in gastro-intestinal absorption
      of DEX and the issue of noncompliance in patients undergoing the dexamethasone
      suppression test (DST). Both routes of DEX administration were equally effective
      in suppressing plasma cortisol levels below 5 micrograms/dl, the customary
      criterion level. Both routes of DEX administration also significantly decreased
      the percent and absolute number of CD4+ cells, the CD4+/CD8+ ratio, and the
      percent and absolute number of virgin, but not of memory, CD4+ cells.

PMID- 1359601
TI  - Psychoneuroendocrinology of aging: The brain as a target organ of hormones.
      Proceedings of a workshop. Parma, Italy, 1991.

PMID- 1359599
TI  - Pulsatile LH secretion in women with premenstrual syndrome (PMS): evidence for
      normal neuroregulation of the menstrual cycle.
AB  - The premenstrual syndrome (PMS) has been proposed to result from excessive
      exposure to and/or withdrawal of brain opioid activity during the luteal phase.
      Because hypothalamic opioids are believed to modulate GnRH secretion, in part
      under the influence of ovarian steroids, we performed longitudinal studies of
      gonadotropin and ovarian steroid secretion across ovulatory, symptomatic cycles
      of 17 PMS patients and 8 normal volunteers. Pulsatile LH secretion was measured
      every 10 min for 8 hr at times when central opioid activity was expected to be
      low (early follicular phase), high (mid-luteal phase; ML), and declining (late
      luteal phase). In both subject groups, a cycle-phase effect was observed for LH
      pulse frequency (p = < 0.001) and amplitude (p = 0.002), and for the transverse
      mean concentrations of LH (p = 0.05), FSH (p < = 0.001), estradiol (E2) (p = <
      0.001) and progesterone (P) (p = < 0.001). ML P secretion in PMS patients was
      pulsatile, and mean concentrations (over 30-60 min) were similar to those of
      normal controls. The changes in pulsatile LH secretion across the cycle were not
      different in the PMS patients compared to the normal women, though mean FSH in
      the ML phase was higher in the PMS group (p = < 0.05). The similar changes in
      luteal LH pulse frequency fail to provide evidence that GnRH secretion is
      impaired, thus challenging the view that the neuroregulation of the menstrual
      cycle in women with PMS is markedly altered.

PMID- 1359600
TI  - Alpha-2-adrenoceptor control of cortisol and ACTH in normal volunteers:
      preliminary open trial of the effects of acute and chronic idazoxan.
AB  - To examine the role of alpha 2-adrenoceptors in the control of cortisol and ACTH,
      hormone responses to the selective alpha 2-antagonist idazoxan were studied in 12
      normal volunteers. Plasma cortisol and ACTH were measured from 0930h-1230h on
      three occasions: before, on the 1st day, and on the 22nd day of an open treatment
      trial with idazoxan 40 mg administered three times per day. Compared with
      pretreatment cortisol levels, acute but not chronic idazoxan treatment attenuated
      the normal diurnal fall in plasma cortisol. Plasma ACTH concentrations were not
      altered by either dose of idazoxan. The attenuation of the diurnal fall in
      cortisol after acute idazoxan may be mediated through increased central
      availability of norepinephrine, and is similar to responses after high doses of
      the less selective alpha 2-antagonist yohimbine. Activity of central
      noradrenergic neurons appears to be reduced or normalized by chronic idazoxan,
      indicated by restoration of the normal diurnal fall in cortisol.

PMID- 1359602
TI  - Psychoneuroendocrinology of aging: the brain as target organ of hormones.

PMID- 1359603
TI  - Psychopathological aspects of neuroendocrine diseases: possible parallels with
      the psychoendocrine aspects of normal aging.
AB  - Psychological impairments can occur during the course of major endocrine
      diseases. These impairments range from mild affective-cognitive-behavioral
      disturbances to frank psychoses. The former are rather specific for each hormonal
      disorder and disappear with the hormonal correction. The latter, instead, seem to
      be quite nonspecific and include depression, mania, schizophrenia-like and
      organic brain syndromes which appear at random in each endocrinopathy, not always
      regressing with hormonal recovery, and apparently correlating more with the
      severity than with the nosographic classification of the metabolic disturbances.
      It is suggested that age-related physiological changes of hormonal and
      psychological patterns mimic those occurring in neuroendocrine diseases and that,
      possibly, common brain biochemical changes may underlie the two phenomena.

PMID- 1359604
TI  - Effects of hypothalamic peptides on the aging brain.
AB  - The hypothalamic peptide hormones, TRH, LHRH (GnRH), CRH, GHRH, and GHIRH
      (somatostatin), influence the release of the anterior pituitary hormones, which
      in turn promote the release of target endocrine gland hormones and other
      metabolites. These latter compounds feed back to the brain to help control the
      secretion of the hypothalamic hormones. This is a dynamic interaction that is
      influenced by the aging process: Most of these hormones systems become less
      responsive with advancing age, due to decreased function of peptide-containing
      secretory neurons, a loss of hormone receptor sensitivity, and/or a reduction in
      the output of the target endocrine glands. That the hypothalamic peptides
      themselves can influence brain function is supported by the fact that most are
      found in areas of the brain other than the hypothalamus and that receptors for
      them exist in these other areas. For example, CRH is contained in a number of
      central neural systems that can influence behavior, including limbic areas, the
      hypothalamus, locus coeruleus, median raphe nuclei, and cortical interneurons.
      CRH has been shown to be anxiogenic in animal models, and its effect can be
      blocked by CRH receptor antagonists. CRH content in the locus coeruleus is
      particularly increased by stress and may influence norepinephrine
      neurotransmitter function in this structure. In aging there is a gradual
      reduction of the sensitivity of the brain to the negative feedback of
      corticosteroids, such that CRH secretion becomes somewhat increased under basal
      conditions. The behavioral effects of this change are unclear, however, as is the
      influence of stress-related activation of CRH, ACTH, and glucocorticoid secretion
      on behavior in the elderly. Other hypothalamic peptides have different patterns
      of change with aging, and some are markedly altered in pathological conditions;
      for example, in Alzheimer's disease the content of CRH and somatostatin in
      certain brain areas is decreased. However, whether the changes in hypothalamic
      peptides precede or follow the pathological behavioral changes, and how they
      participate in the changes, is still unclear.

PMID- 1359606
TI  - Psychoneuroendocrinoimmunology: the basis for a novel therapeutic approach in
      aging.
AB  - Along with the nervous and the endocrine systems, the immune system is one of the
      three major integrative systems in higher organisms. Growing evidence
      demonstrates an intimate relationship between the immune system and the endocrine
      and nervous systems: The psychoneuroendocrine system can influence the immune
      response and thereby the capacity of the organism to cope with illness, and the
      immune system can have an impact on neuroendocrine function. Such cross-talk
      among systems is dependent upon feedback loops working to maintain homeostatic
      equilibrium.

PMID- 1359605
TI  - The brain as a target organ of gonadal steroids.
AB  - Gonadal steroids have many effects in the central nervous system. Through a
      feedback mechanism, they influence the synthesis and release of hypothalamic
      gonadotropin-releasing hormone (GnRH) and/or pituitary gonadotropic hormones
      (luteinizing hormone, LH, and follicle stimulating hormone, FSH). Endogenous
      opioid peptides (EOPs) represent one of the key factors modulating the activity
      of sex steroids on the hypothalamus-pituitary-gonadal (HPG) axis. In particular,
      these peptides control the secretion of LH by inhibiting the activity of the
      hypothalamic neurons which produce GnRH. The EOP effect is dependent on the
      steroid hormone milieu, as shown by different responses to naloxone
      administration, both in animals and in humans. For the naloxone-induced increase
      in LH secretion to occur, relatively high levels of sex steroids are required. In
      humans, LH release is absent before sexual maturation. In fertile women, naloxone
      administration increases LH levels in the luteal phase but not in the follicular
      phase. In the postmenopausal period, naloxone has no effect on LH release;
      estrogen/progestin therapy does restore the LH response.

PMID- 1359607
TI  - Symposium: The Molecular basis for Radiation Effects on Cell Progression through
      the Cell Cycle. March 1992.

PMID- 1359608
TI  - Successful Maternal Recognition of Pregnancy: Signalling between the Conceptus
      and the Maternal System. Symposium proceedings. Honolulu, Hawaii, 1-3 July 1991.

PMID- 1359609
TI  - Autoradiographic visualization of the natriuretic peptide receptor-B in rat
      tissues.
AB  - Natriuretic peptide receptor-B (NPRB) was visualized in rat tissues by in vitro
      autoradiography, using its putative physiological agonist C-type natriuretic
      peptide (CNP). In initial studies, we determined that atrial natriuretic peptide
      (ANP) is not a suitable ligand for labeling the NPRB: in tissues reported to
      contain NPRB transcripts, CNP did not inhibit [125I]ANP binding except to NPRC
      sites. Therefore, to visualize the NPRB we used 125I[Tyr(o)]-CNP as a radioligand
      with an excess of NPRC-blocking peptide: C-ANP. With this approach we detected
      the highest number of NPRB-like sites in the pars intermedia of the pituitary
      gland. A large number of these sites were present in pituitary neural and
      anterior lobes, area postrema, adrenal medulla and cortex. A moderate NPRB
      population was observed in the subfornical organ, plexiform layer of the
      olfactory bulb and kidney. Low concentrations of NPRB were noted in the
      cerebellum and cerebrum but not in the choroid plexus and pia-arachnoid.
      Saturation experiments performed on cerebellum sections revealed a very low
      concentration (Bmax 4.8 fmol/mg protein) of high affinity (Kd 1.2 nM) NPRB-like
      sites. This study is the first demonstration of 125I[Tyr(o)]-CNP binding sites
      with characteristics of the NPRB in intact tissues.

PMID- 1359610
TI  - Achlorhydria induced changes in gastrin, somatostatin, H+/K(+)-ATPase and
      carbonic anhydrase in the sheep.
AB  - Gastrin, somatostatin, H+/K(+)-ATPase and carbonic anhydrase are principal
      elements of acid secretion. We investigated in the conscious sheep the effect of
      24 h omeprazole (an H+/K(+)-ATPase inhibitor) infusion on these elements at the
      level of synthesis, storage and secretion. Omeprazole inhibited acid secretion-pH
      increased from 3.0 to 7.1 at 24 h. Plasma amidated and glycine extended gastrin
      increased 3-fold while the ratio of amidated to glycine extended gastrins (4:1)
      remained unchanged. Despite the increase in circulating gastrin, antral gastrin
      concentration and mRNA did not change significantly. Gastrin-17 (amidated and
      glycine extended) was the predominant form in the circulation and antrum,
      although there were preferential increases in larger forms following omeprazole
      treatment. Omeprazole had no effect on somatostatin mRNA or peptide levels in the
      fundus. Similarly, plasma somatostatin remained unchanged. However, antral
      somatostatin increased significantly (63%) following omeprazole treatment
      accompanied by a 4-fold increase in its mRNA. Fundic H+/K(+)-ATPase mRNA was
      unchanged but a significant increase (87%) in carbonic anhydrase II mRNA was
      observed. Omeprazole induced hypergastrinaemia occurred without a measurable
      reduction in storage or increased synthesis of gastrin at 24 h. Increased antral
      somatostatin synthesis and storage may result from stimulation by plasma gastrin
      on antral D cells, independent of acid. The rise in carbonic anhydrase II mRNA in
      the absence of any change in H+/K(+)-ATPase mRNA may reflect the differential
      sensitivity of the genes encoding these two enzymes to the stimulatory action of
      gastrin.

PMID- 1359611
TI  - Vascular control of the pig nasal mucosa: distribution and effect of somatostatin
      in relation to noradrenaline and neuropeptide Y.
AB  - By means of immunohistochemistry and radioimmunoassay (RIA), we have investigated
      the possible occurrence of somatostatin (SOM)-like immunoreactivity (-LI) in the
      autonomic innervation of the pig nasal mucosa. SOM-immunoreactive (-IR) fibres
      were present around nasal arteries, arterioles and venous sinusoids. Double
      labelling experiments revealed that SOM-LI was co-localized with the
      noradrenaline (NA) markers tyrosine hydroxylase and dopamine-beta-hydroxylase as
      well as with neuropeptide Y (NPY) in a subpopulation of neurons in the superior
      cervical sympathetic ganglion and in perivascular nerve terminals. Furthermore,
      SOM-LI was also present in perivascular fibres containing vasoactive intestinal
      polypeptide (VIP) and NPY of presumably parasympathetic origin. The
      parasympathetic fibres that were associated with glands contained peptide
      histidine isoleucine (PHI), VIP and NPY but not SOM, suggesting that in the nasal
      mucosa SOM-IR is restricted to perivascular nerves. As revealed by RIA, the
      content of SOM-LI in biopsies of both nasal mucosa and superior cervical
      sympathetic ganglion was about 12 pmol/g and the reverse phase HPLC
      characterisation of SOM-LI shown two separate peaks for SOM-28 and SOM-14. In
      thiopentone anaesthetized pigs (n = 10), local intra-arterial (i.a.) infusion of
      SOM (1-14) induced dose-dependent, long lasting and parallel reduction of the
      nasal arterial blood flow, the volume of the nasal mucosa (reflecting capacitance
      vessel function) and decrease of the laser Doppler flowmeter signal (reflecting
      superficial nasal mucosal blood flow). These functional responses were not
      modified after pretreatment with the alpha-adrenoceptor antagonist
      phenoxybenzamine (1 mg kg-1 i.a.) whereas the effects of NA were almost
      abolished. SOM (6.10(-6) mol, i.a.) did not influence the nasal vascular
      responses to single impulse stimulation of the nasal sympathetic nerve supply
      providing no evidence for prejunctional activity in spite of clear-cut vascular
      effects. It is concluded that SOM-LI is co-localized with NA and NPY in
      sympathetic nerves and with VIP/NPY in parasympathetic perivascular nerves of the
      pig nasal mucosa. Since SOM evokes vasoconstriction via non-adrenergic
      mechanisms, this peptide should also be considered when discussing mediator
      candidates for the neural regulation of the nasal vascular bed.

PMID- 1359612
TI  - Dynorphin B-like immunoreactivity in gastroduodenal biopsy specimens from
      gallstone patients.
AB  - Dynorphin B-like immunoreactivity (ir-dyn B) was measured by a validated radio
      immunoassay in gastroduodenal biopsy specimens from control and gallstone
      patients. Levels were significantly lower in acetic acid extracts of specimens of
      the transverse portion of the duodenum from gallstone patients. Gel permeation
      chromatography showed that almost all ir-dyn B in duodenal samples corresponded
      to a molecular form co-eluting with authentic dyn B. Duodenal extracts from
      gallstone patients had less of this form. Reverse-phase high performance liquid
      chromatography of the pooled gel chromatography fractions showed up a molecular
      form with the same retention time as synthetic dyn B which was significantly less
      in fractions from duodenal extracts of gallstone patients. These results indicate
      the occurrence of dyn B in the human gastrointestinal tract; however, at this
      stage of our understanding, no causal relationship can be demonstrated with
      functional alterations of the biliary tree.

PMID- 1359613
TI  - Somatostatin inhibition of phosphoinositides turnover in isolated rat acinar
      pancreatic cells: interaction with bombesin.
AB  - The effects of somatostatin-14 and bombesin on [3H]inositol phosphate
      accumulation were studied in 24 h myo-[3H]inositol-prelabeled cultured rat acinar
      cells. Bombesin, 10 nM, stimulated basal formation of phosphatidyl monophosphate
      (InsP1), phosphatidyl 4,5-biphosphate (InsP2) and inositol 1,4,5-triphosphate
      (InsP3) by 128 +/- 5.2%, 147 +/- 10% and 155 +/- 5%, respectively. At 5 s, the
      ED50 value for InsP3 stimulation was 0.70 +/- 0.2 nM. This stimulation was partly
      blocked (64 +/- 0.04% inhibition) by 10 ng/ml Bordetella pertussis toxin. In
      contrast to bombesin, somatostatin, 10 nM, inhibited basal InsP1, InsP2 and InsP3
      formation. At 5 s, the inhibition degree for InsP3 was 18 +/- 2.5% and the IC50s
      values 1 +/- 0.09 nM, 1 +/- 0.12 nM and 0.07 +/- 0.005 nM for InsP1, InsP2 and
      InsP3, respectively. Bombesin-stimulated InsP3 formation was also inhibited by
      somatostatin. At 5 s, the inhibition degree was 85 +/- 3.5% at 10 nM and the IC50
      value, 0.10 +/- 0.05 nM. Furthermore, somatostatin inhibition of bombesin
      stimulation was partly blocked (66 +/- 4% inhibition) by Bordetella pertussis
      toxin. These data therefore suggest that the acinar pancreatic cells contain a
      somatostatin receptor exerting a negative control on basal and bombesin receptor
      stimulated phosphatidyl inositol turnover.

PMID- 1359614
TI  - [Update on benzodiazepines].
AB  - The Authors shortly review the benzodiazepine (BDZ) pharmacology and therapeutic.
      They start from the supposed mechanism of action, then the main indications,
      counterindications and side effects are reported. Finally, the pharmacokinetic
      and general classification of the drugs are examined.

PMID- 1359615
TI  - Neuroendocrine evidence for antagonism of serotonin and dopamine receptors by
      olanzapine (LY170053), an antipsychotic drug candidate.
AB  - Olanzapine, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-B]
      [1,5]benzodiazepine (LY170053), antagonized the quipazine-induced elevation of
      serum corticosterone concentration in rats with an ED50 value of 0.57 mg/kg i.p.
      LY170053 was less potent in antagonizing the pergolide-induced elevation of serum
      corticosterone concentration in rats, and increases in corticosterone elicited by
      olanzapine alone at higher doses complicated the precise estimate of an ED50
      value, which was approximately 3 mg/kg. These relative potencies in blocking
      quipazine and pergolide effects are taken as indices of antagonism of serotonin
      5HT2 and of dopamine D2 receptors, respectively. Olanzapine is more potent than
      clozapine in blocking 5HT2 and D2 receptors, and its ability to block these
      receptors supports its possible usefulness as an antipsychotic drug.

PMID- 1359616
TI  - Neonatal administration of L-cysteine does not produce long-term effects on
      neurotransmitter or neuropeptide systems in the rat striatum.
AB  - Previous studies by other investigators have shown that neonatal administration
      of high doses of L-cysteine produces within 6 hrs morphological damage to neurons
      in many areas of the brain including the striatum; the damage could be blocked by
      NMDA antagonist MK-801. These studies implicated a potential involvement of this
      amino acid in neurodegenerative processes including Parkinsonism. The present
      study attempted to elucidate whether L-cysteine produces long-term changes in
      neurotransmitter (dopamine; 5-hydroxytryptamine) or neuropeptide (Met5
      enkephalin; dynorphin A (1-8); substance P) systems as a corollary to neonatal
      treatment with L-cysteine. L-cysteine (0.5 or 1 g/kg, s.c.) was administered to 4
      day old rat pups and sacrificed 35 days later. The striatal levels of amines and
      neuropeptides were determined by HPLC and radioimmunoassay respectively. L
      Cysteine treatment alone or after a pretreatment with MK-801 (1 mg/kg, s.c.)
      failed to produce any significant changes in the parameters studied. The results
      indicate that neonatal administration of L-cysteine does not appear to produce
      long-term effects on major neuroregulator systems of the striatum.

PMID- 1359617
TI  - Effects of the serotonin-antagonist ketanserin on the function of ischaemic and
      normally perfused myocardium and modification by beta-1-blockade in anaesthetized
      normotensive dogs.
AB  - The 5-HT-2 antagonist ketanserin (KAS) has been successfully used to treat acute
      hypertension in coronary bypass surgery. The present study was performed to
      investigate the effect of KAS on ischaemic myocardium. In 11 anaesthetized
      (piritramide) dogs, systolic contraction (sdL) and end-diastolic length (edL) of
      myocardium supplied by the left descending coronary artery (LAD) and the left
      circumflex coronary artery (LCX) were measured by sonomicrometry simultaneously
      with aortic pressure (AoP), left ventricular dP/dtmax and end-diastolic pressure
      (LVedP), heart rate (HR), stroke volume, and LAD flow (QLAD). Regional ischaemia
      to decrease sdLLAD (-48%) was achieved by LAD stenosis (QLAD -47%).
      Concomitantly, edLLAD increased by 8%. However, the other variables did not
      change. Then KAS was given i.v. (0.15 + 0.15 + 0.30 + 0.6 mg/kg) at 15-min
      intervals. Following KAS, prestenotic sdLLAD recovered in a dose-dependent
      manner. LVedP and edLLAD decreased, sdLLCX increased, and the other variables
      were not affected. This functional recovery of ischaemic myocardium was
      attenuated by pretreatment with metoprolol (MET, 1 mg/kg) prior to LAD stenosis.
      The ischaemic area was not irreversibly damaged, however, as proven by the
      recovery of prestenotic sdLLAD values after release of the stenosis. The improved
      systolic shortening of ischaemic myocardium following KAS did not result from
      restored QLAD due to post-stenotic vasodilation or break up of platelet
      aggregates (QLAD did not increase) or from reduced afterload (AoP did not
      decrease). Obviously, it was mediated by beta-1-receptors, as shown by the
      attenuation of the beneficial effect of KAS by pretreatment with MET.

PMID- 1359618
TI  - Changes in hepatic lipogenic enzyme activities in voles and mice treated with
      monosodium aspartate.
AB  - Changes in activities of hepatic lipogenic enzymes, ATP citrate lyase and acetyl
      CoA carboxylase, were measured in voles and C57BL mice following neonatal
      administration of monosodium aspartate (MSA). Hepatic lipogenic enzyme activities
      in voles were considerably lower than those in mice; these low activities were
      considered to be one of the characteristics of voles as a herbivore. In the MSA
      treated voles and mice, the plasma insulin concentrations increased
      significantly. The MSA-treated mice showed remarkable obesity and increased
      lipogenic enzyme activities. In the MSA-treated voles, signs of obesity were not
      observed and hepatic ATP citrate lyase activity increased significantly; acetyl
      CoA carboxylase activity did not increase.

PMID- 1359620
TI  - [Pentoxifylline in the treatment of AIDS].

PMID- 1359619
TI  - [Low doses of azidothymidine in the treatment of HIV-1 virus infection].
AB  - A group of 26 patients (18 males and 8 females) infected with HIV (42% through
      sexual route and 58% through blood/blood products transfusion) was prospectively
      studied to assess the efficacy of low doses (300 mg/day) of AZT combined (n = 15)
      or not (n = 11) with ACV (600 mg/day). According to CDC stages, 12% were in stage
      II, 73% in stage III and 15% in stage IV. Patients were followed for a maximum of
      156 weeks. An objective response was observed in all patients who improved
      significantly in: performance status (Karnofsky 74.5 versus 97.6%, p less than
      0.01), weight 58.9 versus 68.6 kg, p less than 0.01), and absolute CD4 T cell
      count (329/microL versus 480/microL, p less than 0.01). The levels of hemoglobin
      dropped after treatment (12.8 versus 11.5, p less than 0.01). Median survival was
      114 weeks for all the group. With the exception of granulocytopenia in 42% of
      patients treated with AZT + ACV versus only in 22% of those treated solely with
      AZT (p = 0.02), similar effects were recorded in both treatments: 114-week
      survival was 60% for those treated solely with AZT, whereas 156-week survival was
      93% for those treated with AZT + ACV (p NS), but the response was better for the
      combination of antivirals in the group of patients with more than 200 CD4
      cells/microL at diagnosis as compared with those with less than 200 cells (110
      week survival of 100% versus 50% respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359621
TI  - Estimating prevalence by group testing using generalized linear models.
AB  - A method is described for estimating prevalence by group testing using
      generalized linear models. This provides a simple way of analysing such data
      using widely available software. Existing methodology to correct for
      overdispersion using quasi-likelihoods is applied to the group testing model. The
      methods are illustrated by an estimation of salmonella contamination in eggs, and
      of yellow fever virus infection in a mosquito population.

PMID- 1359623
TI  - [Asthma, allergy, current aspects: IgE, atopy and parasites. Report of a 3A
      conference of January 25, 1992].

PMID- 1359622
TI  - [Falls as a side effect of drugs].
AB  - Because of the smaller functional resources, the risk for falls in elderly
      persons is significantly increased when they take sedative anxiolytics with long
      half life, antipsychotics, antidepressants and, not so well documented,
      antihypertensives. Nonpharmacological strategies are, therefore, the treatment of
      choice for insomnia, depression and agitation in the elderly.

PMID- 1359624
TI  - [Stages of drug treatment in threatened premature labor].

PMID- 1359625
TI  - [Treatment of threatened premature labor by beta mimetic drugs. Experience at the
      Hotel-Dieu].

PMID- 1359626
TI  - [Usefulness of beta mimetic treatment in threatened premature labor].

PMID- 1359627
TI  - [What treatment in threatened premature labor?].

PMID- 1359628
TI  - [Fetal advantages and benefits of the treatment of threatened premature labor by
      beta mimetics].

PMID- 1359629
TI  - Disposition of mesalazine from mesalazine-delivering drugs in patients with
      inflammatory bowel disease, with and without diarrhoea.
AB  - The disposition of mesalazine from the azo compounds sulphasalazine and
      olsalazine (Dipentum) and from the slow-release mesalazine drugs Pentasa, Asacol,
      and Salofalk was studied in 20 patients with inflammatory bowel disease. Ten of
      them had diarrhoea, and 10 had normal stools. On the last 2 days of a 7-day
      maintenance treatment with each of the study drugs urine and faeces were
      collected for determination of mesalazine, acetyl-mesalazine, and unsplit azo
      compound. In patients with and without diarrhoea the urinary and the faecal
      excretion of acetyl-mesalazine was lowest during treatment with olsalazine. The
      proportion of acetyl-mesalazine in faeces was highest during treatment with
      Pentasa in both groups. The presence of diarrhoea was associated with a decrease
      in the proportion of acetyl-mesalazine in faeces during treatment with all drugs,
      not significant only for Pentasa. The proportion of unsplit azo compound in
      faeces increased in the case of diarrhoea to almost 50%. It is concluded that in
      patients with inflammatory bowel disease diarrhoea substantially influences the
      disposition from all these drugs except Pentasa.

PMID- 1359630
TI  - Clinical evaluation of pancreatic cancer-associated mucin expressing CA19-9,
      CA50, Span-1, sialyl SSEA-1, and Dupan-2.
AB  - We have previously described the purification and partial characterization of a
      new pancreatic cancer-associated antigen, a pancreatic cancer-associated mucin
      expressing CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2. This study describes
      the clinical evaluation of various assay systems for this antigen which depend on
      measuring respective serum levels. Elevated levels of antigen were detected in
      the sera from both patients with malignant and non-malignant diseases. However,
      elevated serum levels of CA19-9 and Lewisa and Lewisb epitopes on moieties were
      restricted to pancreatic and biliary tract cancers, although adequate sensitivity
      was not attained. Coordinate evaluation of these three markers improved the
      sensitivity to some extent without loss of specificity for the diagnosis of
      pancreatic and biliary tract cancers, because of the heterogeneity of the
      coexpression of these epitopes. We developed additional assay systems with a
      combination of this antigen and two lectins (Bauhinia purpurea (BPA) and Vicia
      villosa (VVA)). Elevated levels of BPA- and VVA-reactive antigens were detected
      in 41% and 31%, respectively, of pancreatic cancer sera samples. Few patients
      with chronic pancreatitis had an elevated serum level of either antigen, and
      higher elevated levels of these markers were restricted to the sera of patients
      with malignancies. Our results suggest that this antigen is found in the sera of
      patients with various conditions and in the sera of normal subjects but that
      antigens bearing CA19-9 or Lewisa or Lewisb epitopes and an altered carbohydrate
      structure recognized by BPA and VVA lectins are preferentially present in the
      sera of patients with pancreatic and other malignancies.

PMID- 1359631
TI  - Vagal control of the release of somatostatin, vasoactive intestinal polypeptide,
      gastrin-releasing peptide, and HCl from porcine non-antral stomach.
AB  - We studied the secretion of somatostatin and HCl and the release of vasoactive
      intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP) from isolated,
      vascularly perfused, porcine non-antral stomach. Electric vagus stimulation
      increased acid secretion and the release of VIP and GRP and inhibited
      somatostatin secretion as determined in the venous effluent. Atropine abolished
      the HCl response and reversed the somatostatin inhibition to a three-fold
      increase, whereas GRP and VIP responses were unchanged. Both intra-arterial
      carbachol (10(-6) M) and GRP (10(-8) M) increased acid secretion and inhibited
      somatostatin secretion. VIP (10(-8) M) increased somatostatin secretion and had
      no effect on acid secretion. By immunohistochemistry, somatostatin was localized
      to both open-type and closed-type cells equally spread in the various parts of
      the gastric glands without particular relation to the parietal cells. Numerous
      GRP- and VIP-immunoreactive nerve fibers were seen between the glands. It is
      concluded that the fundic and antral secretion of somatostatin, investigated in a
      previous study, are differently regulated. The relation of fundic somatostatin
      release to acid secretion seems to be complex.

PMID- 1359632
TI  - Horizons in gastroenterology. Proceedings of an International meeting. Evian,
      France, 21-24 June 1992.

PMID- 1359633
TI  - Gender differences in tardive dyskinesia: a critical review of the literature.
AB  - We analyzed data from 76 selected studies on prevalence of tardive dyskinesia
      (TD), published through 1989. The primary focus was on gender differences. The
      overall prevalence of TD in the 39,187 patients included in these reports was
      24.2 percent, and prevalence was significantly higher in women (26.6%) than in
      men (21.6%). The gender difference in TD prevalence appeared to narrow
      intriguingly in more recent studies. Overall, the TD prevalence seemed to reach
      its peak in the 50-70-year-old age group in men and continued to rise after age
      70 in women. Also, women tended to have more severe TD than men. Spontaneous
      dyskinesia too was found to be more common in women. The material was also
      analyzed for cultural differences by comparing studies in four continents: North
      America, Europe, Africa, and Asia. Although grouping together studies from
      different countries in a continent into a single group is somewhat problematic,
      we found that Asian patients had lower prevalence of TD than North American,
      European, and African patients. Limitations of our review (including differences
      among studies in diagnostic criteria, observer bias, etc.) as well as possible
      explanations for the reported differences in the risk for TD are discussed.

PMID- 1359634
TI  - Anti-Inflammatory Efficacy versus Gastrointestinal Safety: A Dilemma Resolved?
      Proceedings of a symposium at the XIIth European Congress of Rheumatology.
      Budapest, Hungary, 2 July 1991.

PMID- 1359635
TI  - Influence of acetylator status on sulphasalazine efficacy and toxicity in
      patients with rheumatoid arthritis.
AB  - The influence of acetylator status on the therapeutic efficacy and the toxicity
      of sulphasalazine (SASP) was assessed in 106 patients with rheumatoid arthritis
      (RA). Changes of indices of disease activity after 6 months, and progression of
      erosions after 2 years of SASP treatment were similar in fast and slow
      acetylators. Incidence and nature of withdrawals and side-effects, and
      requirement for intra-articular steroid injections or combination therapy due to
      poor response to SASP were almost identical in the two groups. A significant
      increase of the hepatic enzyme aspartate transaminase was noted mainly in slow
      acetylators, but was not associated with clinical disease. These results suggest
      that acetylator status does not relate significantly to either the efficacy or
      the toxicity of SASP in RA. It is possible that hepatic metabolism is affected by
      SASP, particularly in slow acetylators, but this does not lead to clinically
      identifiable problems.

PMID- 1359636
TI  - [Dental imaging].

PMID- 1359637
TI  - Unlikely messengers. How do nerve cells communicate?

PMID- 1359638
TI  - Association of selected social, environmental and constitutional factors to blood
      lead levels in men aged 55-75 years.
AB  - Blood lead (B-Pb) levels were determined in 1802 out of 1856 non-occupationally
      exposed men aged 55-75 years living in the Rome area who participated, between
      1989 and 1990, in an epidemiological survey for coronary heart disease (New Risk
      Factors Project). The median B-Pb level was 113 micrograms/l (10th-90th centiles:
      74-180 micrograms/l) and only 0.7 per cent (n = 14) of the subjects had B-Pb
      values higher than 300 micrograms/l. B-Pb levels were significantly and
      positively associated to alcohol consumption. Moderate and heavy drinkers had
      median B-Pb level of 143 micrograms/l (10th-90th centiles: 92-233) and 165
      micrograms/l (10th-90th centiles: 102-285) respectively, whereas non-drinkers had
      a median B-Pb level of 96 micrograms/l (10th-90th centiles: 66-143). The
      influence of smoking habits was less relevant. Subjects who never smoked and
      subjects smoking more than 20 cigarettes daily had median B-Pb levels of 103 and
      133 micrograms/l, respectively. Individuals classified as habitual car-drivers
      had slightly higher Pb levels than non-drivers. Subjects classified as manual
      workers had higher B-Pb levels in comparison with non-manual workers and retired
      subjects. B-Pb levels were directly related to HDL-cholesterol (HDL-C, r =
      0.2252) and gamma-glutamyltransferase (gamma-GT, r = 0.2207) serum levels. The
      alleged alcohol consumption was more related to B-Pb level (r = 0.3848) than to
      serum level of HDL-C (r = 0.2474) or gamma-GT (r = 0.2469). A significant
      correlation (r = 0.2409) also existed between B-Pb and blood cadmium levels (B
      Cd). Subjects with a low Gaensler ratio, an index of respiratory function, had
      higher B-Pb levels. In multiple regression analyses alcohol intake was the most
      important predictor of B-Pb level, explaining more (14.27%) of the total variance
      than did B-Cd (4.98%), HDL-C (1.89%), driving habits (1.46%), gamma-GT (1.09%),
      skinfold thickness (0.96%), and Gaensler index (0.38%). The risk ratio of having
      B-Pb level higher than 180 micrograms/l (90th centile of B-Pb distribution in our
      subjects) was 5.3 (95% CI: 2.7-10.4) for drinkers versus non-drinkers and 1.9
      (95% CI: 1.2-3.1) for current smokers versus subjects who had never smoked. B-Pb
      was, at least in our subjects, a more specific and sensitive objective index of
      alcohol consumption than gamma-GT and HDL-C.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1359639
TI  - A comprehensive genetic linkage map of the human genome. NIH/CEPH Collaborative
      Mapping Group.

PMID- 1359640
TI  - The human Y chromosome: overlapping DNA clones spanning the euchromatic region.
AB  - The human Y chromosome was physically mapped by assembling 196 recombinant DNA
      clones, each containing a segment of the chromosome, into a single overlapping
      array. This array included more than 98 percent of the euchromatic portion of the
      Y chromosome. First, a library of yeast artificial chromosome (YAC) clones was
      prepared from the genomic DNA of a human XYYYY male. The library was screened to
      identify clones containing 160 sequence-tagged sites and the map was then
      constructed from this information. In all, 207 Y-chromosomal DNA loci were
      assigned to 127 ordered intervals on the basis of their presence or absence in
      the YAC's, yielding ordered landmarks at an average spacing of 220 kilobases
      across the euchromatic region. The map reveals that Y-chromosomal genes are
      scattered among a patchwork of X-homologous, Y-specific repetitive, and single
      copy DNA sequences. This map of overlapping clones and ordered, densely spaced
      markers should accelerate studies of the chromosome.

PMID- 1359641
TI  - Comparative genomic hybridization for molecular cytogenetic analysis of solid
      tumors.
AB  - Comparative genomic hybridization produces a map of DNA sequence copy number as a
      function of chromosomal location throughout the entire genome. Differentially
      labeled test DNA and normal reference DNA are hybridized simultaneously to normal
      chromosome spreads. The hybridization is detected with two different
      fluorochromes. Regions of gain or loss of DNA sequences, such as deletions,
      duplications, or amplifications, are seen as changes in the ratio of the
      intensities of the two fluorochromes along the target chromosomes. Analysis of
      tumor cell lines and primary bladder tumors identified 16 different regions of
      amplification, many in loci not previously known to be amplified.

PMID- 1359642
TI  - Reductase activity encoded by the HM1 disease resistance gene in maize.
AB  - The HM1 gene in maize controls both race-specific resistance to the fungus
      Cochliobolus carbonum race 1 and expression of the NADPH (reduced form of
      nicotinamide adenine dinucleotide phosphate)-dependent HC toxin reductase (HCTR),
      which inactivates HC toxin, a cyclic tetrapeptide produced by the fungus to
      permit infection. Several HM1 alleles were generated and cloned by transposon
      induced mutagenesis. The sequence of wild-type HM1 shares homology with
      dihydroflavonol-4-reductase genes from maize, petunia, and snap-dragon. Sequence
      homology is greatest in the beta alpha beta-dinucleotide binding fold that is
      conserved among NADPH- and NADH (reduced form of nicotinamide adenine
      dinucleotide)-dependent reductases and dehydrogenases. This indicates that HM1
      encodes HCTR.

PMID- 1359643
TI  - Nucleotide-iron-sulfur cluster signal transduction in the nitrogenase iron
      protein: the role of Asp125.
AB  - Electron transfer in nitrogenase involves a gating process initiated by MgATP
      (magnesium adenosine triphosphate) binding to Fe-protein. The redox site, an
      4Fe:4S cluster, is structurally separated from the MgATP binding site. For MgATP
      hydrolysis to be coupled to electron transfer, a signal transduction mechanism is
      proposed that is similar to that in guanosine triphosphatase proteins. Based on
      the three-dimensional structure of Fe-protein, Asp125 is likely to be part of a
      putative transduction path. Altered Fe-protein with Glu replacing Asp has been
      prepared and retains the ability for the initial nucleotide-dependent
      conformational change. However, either MgADP or MgATP can induce the shift and Mg
      binding to the nucleotide is no longer essential.

PMID- 1359644
TI  - Prevention of protein denaturation under heat stress by the chaperonin Hsp60.
AB  - The increased synthesis of heat shock proteins is a ubiquitous physiological
      response of cells to environmental stress. How these proteins function in
      protecting cellular structures is not yet understood. The mitochondrial heat
      shock protein 60 (Hsp60) has now been shown to form complexes with a variety of
      polypeptides in organelles exposed to heat stress. The Hsp60 was required to
      prevent the thermal inactivation in vivo of native dihydrofolate reductase (DHFR)
      imported into mitochondria. In vitro, Hsp60 bound to DHFR in the course of
      thermal denaturation, preventing its aggregation, and mediated its adenosine
      triphosphate-dependent refolding at increased temperatures. These results suggest
      a general mechanism by which heat shock proteins of the Hsp60 family stabilize
      preexisting proteins under stress conditions.

PMID- 1359645
TI  - Protection from dementia.

PMID- 1359646
TI  - Dual-target inhibition of HIV-1 in vitro by means of an adeno-associated virus
      antisense vector.
AB  - An adeno-associated virus vector encoding an antisense RNA was used to transduce
      stable intracellular resistance to human immunodeficiency virus-1 (HIV-1) in
      human hemopoietic and non-hemopoietic cell lines. The antisense targets are
      present in all HIV-1 transcripts and include the TAR sequence, which is critical
      for transcription and virus replication, and the polyadenylation signal. Cell
      lines expressing antisense RNA showed up to 95 percent inhibition of gene
      expression directed by the HIV-1 long terminal repeat and greater than 99 percent
      reduction in infectious HIV-1 production, with no detectable cellular toxicity.
      Because of their efficient transcription and inability to recombine with HIV-1,
      adeno-associated virus vectors represent a promising form of anti-retroviral gene
      therapy.

PMID- 1359648
TI  - Elephantiasis: a disease of development in north east Ghana.
AB  - A reconnaissance survey for the presence of lymphatic filariasis is made in 41
      chiefdoms of north east Ghana. Four disease levels are identified culminating in
      hyperendemic disease foci associated with two Government-introduced rice
      irrigation projects. Attention is also drawn to the disease effects of small
      village dams. Multiple concurrent infections are noted. Within the most stricken
      irrigation villages, aspects of concealment, stigma and marriage are considered.
      Failure to control lymphatic filariasis has led to hospital avoidance and neglect
      of the disease jointly by patients, physicians and nurses. Culpability rests with
      the irrigation authority and Government health services. An outline is given of
      possible measures for disease control. A multisectoral policy of 'prevention
      before development' is strongly advocated.

PMID- 1359647
TI  - The time course of glutamate in the synaptic cleft.
AB  - The peak concentration and rate of clearance of neurotransmitter from the
      synaptic cleft are important determinants of synaptic function, yet the
      neurotransmitter concentration time course is unknown at synapses in the brain.
      The time course of free glutamate in the cleft was estimated by kinetic analysis
      of the displacement of a rapidly dissociating competitive antagonist from N
      methyl-D-aspartate (NMDA) receptors during synaptic transmission. Glutamate
      peaked at 1.1 millimolar and decayed with a time constant of 1.2 milliseconds at
      cultured hippocampal synapses. This time course implies that transmitter
      saturates postsynaptic NMDA receptors. However, glutamate dissociates much more
      rapidly from alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptors. Thus, the time course of free glutamate predicts that dissociation
      contributes to the decay of the AMPA receptor-mediated postsynaptic current.

PMID- 1359650
TI  - Beta-cyfluthrin, a synthetic pyrethroid for mosquito control.
AB  - Beta-cyfluthrin (OMS 3051), a new synthetic pyrethroid and one of the
      stereoisomers of cyfluthrin, was studied for insecticidal activity against eight
      mosquito species. Its larvicidal activity with LC50 values of 5.62 x 10(-5) and
      1.19 x 10(-4) mg/l respectively for Culex quinquefasciatus and Aedes aegypti was
      comparable with that of deltamethrin. This pyrethroid was more effective against
      the larvae of Armigeres subalbatus (LC50 - 7.76 x 10(-7)) and the adults of
      Anopheles culicifacies LT50 - 27.76 min at 2.0 mu/cm2) than the other species
      tested. Residual efficacy at 50 mg(ai)/m2 was more persistent (for 14-25 weeks)
      on thatch and asbestos among the four treated surfaces. This compound also
      elicited oviposition deterrent activity at 0.001 mg/l against
      Cx.quinquefasciatus. beta-cyfluthrin is a good insecticide for mosquito control.
      However, care should be exercised while using it as a larvicide in breeding
      habitats considering its toxicity to fish.

PMID- 1359649
TI  - Assessment of sanitation conditions by qualitative sanitation measurement.
AB  - Survey of sanitation conditions by qualitative sanitation measurement were
      carried out in three districts, Chachoengsao Province, Thailand. The sanitation
      of each household was assessed in terms of positive stool examination and scores
      of seven main sanitary activities which were used to classify each household's
      sanitation as hygienic or non-hygienic. Stool collections were made from each
      household's housewife and examined for pathogenic bacteria and parasites. It was
      found that in the qualitative measurement of the household's sanitation as
      hygienic or non-hygienic, most sanitary activities were highly associated with
      the results of stool examination. From consideration of the sensitivity,
      specificity and kappa coefficient of significant sanitary activities as
      predictors and the result of stool examination was used as gold standard, it was
      apparent that a package of all main sanitary activities was the most appropriate
      measurement in the survey to assess sanitation conditions in the community.

PMID- 1359651
TI  - The resting and house frequenting behavior of Mansonia annulifera, Ma. uniformis
      and Ma. indiana, the vectors of Malayan filariasis in Kerala State, India.
AB  - Mansonia annulifera, was recorded to be an endophilic species, preferring to rest
      indoors, while Ma. uniformis was exophilic, having a predilection for outdoor
      resting habitats, eg bushes and shrubs. Ma. indiana did not show a clear
      preference to either of these biotopes. In indoor resting collections, the unfed
      proportion of Ma. uniformis was significantly higher during post-dusk compared to
      day hours (p < 0.05), indicating that this exophilic species enters houses during
      dusk hours for feeding. The full fed proportion was higher during day hours
      compared to dusk/night hours. The semigravid proportion showed a significant
      reduction during post-dusk hours (p < 0.05). These findings suggest that after
      having a blood-meal this species rest indoors and leave the houses for outdoor
      resting sites during the dusk hours on the subsequent night.

PMID- 1359652
TI  - Evaluation of carbon dioxide and 1-octen-3-ol as mosquito attractants.
AB  - CDC Light traps were used to study the attractant effect of CO2 and 1-octen-3-ol
      on trap catches of mosquito populations at three different locations in Malaysia.
      There was a significant increase in the number of mosquitos caught in traps
      baited with CO2 and CO2 with 1-octen-3-ol. The number of mosquitos caught in the
      CDC light trap and in the CDC light trap baited with 1-octen-3-ol alone were very
      few. 1-octen-3-ol and CO2 acted synergistically in attracting significantly
      greater numbers of Culex tritaeniorhynchus. However Anopheles sp. were not very
      attracted to light traps even with attractants added to them.

PMID- 1359653
TI  - Factors affecting compliance with depot injection treatment in the community.
AB  - This study investigated aspects of the community psychiatric care of psychotic
      patients living in inner city areas, and especially those of Afro-Caribbean
      ethnicity. Ethnicity was not found to be a major factor affecting compliance with
      depot injections. More important were variables such as time since first
      treatment and sex. Defaulters from treatment were more likely to be subsequently
      admitted to hospital.

PMID- 1359654
TI  - Complete hamster CAD protein and the carbamylphosphate synthetase domain of CAD
      complement mammalian cell mutants defective in de novo pyrimidine biosynthesis.
AB  - The mammalian CAD gene codes for a 240-kDa multifunctional protein that catalyzes
      the first three steps of de novo pyrimidine biosynthesis. Previously, the longest
      cDNA construct available was missing approximately 500 bp of coding sequence at
      the 5' end, thereby lacking the sequence to encode the entire carbamylphosphate
      synthetase (CPSase) domain. Here, a complete CAD hamster cDNA is constructed,
      placed into a mammalian expression vector, and transfected into hamster cells
      deficient in CAD. Transfectants show coordinately restored levels of all three
      enzyme activities and the presence of full-length CAD protein. A derivative
      construct of the CAD cDNA was generated that should encode only the CPSase
      domain. When transfected into mammalian cells, a protein was synthesized that had
      significant CPSase activity both in vivo and in vitro. The two constructs
      generated in this study will facilitate the study of CAD structure, function, and
      allosteric regulation.

PMID- 1359655
TI  - [Detection of antibodies against T-cell lymphotropic virus HTLV-I/II in Cuban
      patients with chronic renal failure undergoing hemodialysis].

PMID- 1359656
TI  - [Importance of the study of the binding of factor VIII to von Willebrand factor
      in hemophilia A].

PMID- 1359657
TI  - Spinal epidural abscess: a report of 40 cases and review.
AB  - Despite modern medical advances, the morbidity and mortality rates associated
      with spinal epidural abscess remain significant, and the diagnosis often is
      elusive. A retrospective study was undertaken to define better the incidence and
      clinical features of this infection, and to establish current diagnostic and
      therapeutic guidelines. Forty cases of spinal epidural abscess were encountered
      at our institution between July 1979 and March 1991. All medical records and
      radiological images were reviewed. We report a significant increase in the
      incidence of epidural abscess after June 1988 (p = 0.0195). Sixteen patients used
      drugs intravenously, and six had undergone spinal procedures. Twelve patients
      were misdiagnosed in various emergency rooms or clinics and discharged. Localized
      back pain, fever, and neurological deficit remained the typical clinical
      manifestations. Erythrocyte sedimentation rate was elevated uniformly when
      measured (21 cases). Magnetic resonance imaging was diagnostic specifically in 23
      of 24 instances. The majority of patients underwent surgical drainage, but five
      selected patients were managed nonoperatively. The highly variable presentation
      of spinal epidural abscess may confuse the diagnosis and delay indicated surgical
      intervention. Localized back pain in a febrile patient at significant risk for
      epidural abscess warrants erythrocyte sedimentation rate measurement. The
      presence of erythrocyte sedimentation rate elevation or evidence of spinal cord
      compression on physical examination are indications for immediate magnetic
      resonance imaging examination with contrast enhancement. Surgical drainage with
      sustained intravenous antibiotic treatment remains the cornerstone of therapy.
      Nonoperative management may be considered in selected cases.

PMID- 1359658
TI  - [Thrombolysis attains its majority].

PMID- 1359659
TI  - [Beta-adrenoblockaders and pheochromocytoma (a practical case)].

PMID- 1359660
TI  - [The neuroendocrine reactions in patients with chronic bronchitis in a region of
      the northeastern USSR].
AB  - The author describes differences in the manifestations of mutually determined
      reactions of the sympathoadrenal and hypophyseoadrenocortical systems in their
      interaction with the biologically active substance serotonin in healthy persons
      (124) and patients suffering from chronic bronchitis at different times of living
      on the Chukot Peninsula. The most perfect system of the protective effect on the
      part of the neuroendocrine complex can be seen in chronic bronchitis patients
      within the first 3-5 years of living in the North as compared with the reaction
      of the neuroendocrine system in the examined patients with a longer "northern
      record" (10-15 years and more).

PMID- 1359661
TI  - [Hemochromatosis and porphyria cutanea tarda].

PMID- 1359662
TI  - Transplacental exposure to tobacco smoke in human-adduct formation in placenta
      and umbilical cord blood vessels.
AB  - Smokers are exposed to a large number of genotoxic compounds that react with DNA
      to form covalently bound carcinogen-DNA adducts after metabolic conversion to
      their biological active form. Using the P32-postlabeling techniques, tobacco
      smoke related carcinogen--DNA adducts have been demonstrated in DNA isolated from
      human placenta and umbilical cord vein and artery obtained from 11 nonsmoking and
      8 smoking normal healthy women and foetuses. The adduct level was significantly
      higher in tissues from smokers than from nonsmokers (P = 0.021), when all tissues
      were combined. Furthermore, the total adduct level was higher in maternal tissue
      than the level in fetal tissues (P = 0.030). The adduct level in umbilical cord
      vein DNA was significantly lower than in placenta, and marginally lower than in
      umbilical cord artery from the same donor. This suggests that the foetus can
      metabolise some of the genotoxic compounds found in tobacco smoke to DNA-binding
      metabolites. The presence of DNA adducts in foetal tissues is indicative of
      potential genomic damage, that may result in an increased risk for the
      development of serious diseases, like cancer in childhood or later during the
      life span of the individual.

PMID- 1359663
TI  - Effects of reproductive tract glutathione enhancement and depletion on ethyl
      methanesulfonate-induced dominant lethal mutations in Sprague-Dawley rats.
AB  - The effects of altering glutathione (GSH) levels in the male reproductive tract
      have been studied in an attempt to establish a link between chemical-induced
      perturbations in glutathione and susceptibility of spermatozoa to chemical
      insult. Tissue GSH levels were enhanced by a treatment regimen of N
      acetylcysteine (NAC) (250 mg/kg, 4 treatments at 2 h intervals). With this
      treatment, GSH levels in liver, testis, caput epididymis, and cauda epididymis
      were elevated to 126%, 110%, 178%, and 136% of control values. Sexually mature
      male rats were then treated with NAC and challenged with a dose of EMS (100
      mg/kg) to determine if enhanced tissue GSH would protect against EMS-induced
      dominant lethal mutations. Pretreatment with NAC significantly decreased the post
      implantation loss from 7.05 +/- 0.57 with EMS alone to 5.28 +/- 0.47. Conversely,
      a dominant lethal assay was conducted using different doses of phorone
      pretreatment to determine the relative contribution of hepatic versus
      reproductive tract GSH in protecting against EMS-induced dominant lethal
      resorptions. Doses of 100 mg/kg and 250 mg/kg phorone significantly lowered both
      hepatic and reproductive tract GSH while 25 mg/kg lowered only hepatic GSH. These
      three dose levels were used as pretreatments in a dominant lethal study followed
      by a challenge administration of EMS (50 mg/kg), which is a threshold dose of EMS
      for producing dominant lethal mutations. Comparison against controls demonstrated
      a significant potentiation of fetal resorptions in all groups receiving phorone
      pretreatment, including the 25 mg/kg pretreatment group which only lowered
      hepatic GSH prior to EMS challenge. The results of these experiments indicate
      that GSH reserves in the male reproductive tract are insufficient to protect
      developing spermatozoa from damage by alkylating agents in the absence of hepatic
      GSH.

PMID- 1359664
TI  - Lack of synergism among DMAB, BOP, and MNU in induction of carcinomas of the rat
      ventral prostate.
AB  - The present experiment was undertaken to investigate possible synergism in
      induction of rat prostate tumor. F344 rats were repeatedly administered the
      prostate carcinogens 3,2'-dimethyl-4-aminobiphenyl (DMAB),N-nitrosobis(2
      oxopropyl)amine(BOP), and N-methylnitrosourea (MNU) sequentially or together at
      times of hormonal castration induced regenerative cell proliferation of prostate
      epithelial cells. Group 1 animals received two 100 mg/kg doses of DMAB, two 20
      mg/kg applications of BOP, and two times 15 mg/kg of MNU. Groups 2, 3, and 4,
      respectively, received each of the carcinogen treatment alone. Group 5 was given
      6 applications of all three in combination, each at one-third the dose
      administered to the other groups. The results showed a clear synergism in
      enhanced tumor development in the colon but not in the prostate, in which the
      incidence of lesions induced by the three carcinogens was similar to that with
      DMAB alone.

PMID- 1359665
TI  - Strategy of research for cancer--chemoprevention.
AB  - It has been reported that environmental chemicals are important factors in terms
      of both development and prevention of human cancer. For the latter, detection of
      early stages is an essential first step followed by clinical trials for surveying
      populations at risk. Thus a great deal of attention has been focused on these
      areas. However, investigations of possibilities for active prevention of cancer
      development itself form another major project. Chemoprevention of carcinogenesis,
      which means prevention of carcinogenesis by exogenous chemical compounds, has
      been investigated extensively in a variety of organs in animal models. Usually
      attention is concentrated on only one organ. However, antioxidants, such as BHA,
      exert very different effects on different organs, suggesting the necessity of
      whole body approaches to the question of chemoprevention. Furthermore, the
      mechanisms of chemoprevention, including the step of carcinogenesis, i.e.,
      initiation, promotion, progression or whole carcinogenesis steps, in which
      exogenous compounds exert their protective effects, should be considered. A
      medium-term bioassay system and a multi-organ carcinogenesis system, which can be
      used for investigation of potential for cancer chemoprevention, have been
      developed in our laboratory. Dose dependent inhibitory effects were established
      for both BHA and alpha-tocopherol in the medium-term bioassay system, and
      inhibition of small intestinal carcinogenesis by catechins in green tea has also
      been investigated in our multi-organ carcinogenesis protocol. It is extremely
      important for prevention of human cancer that we find new candidates for
      chemopreventive agents using animal studies. This paper reviews published reports
      on chemoprevention, taking into account effective stages, and proposes suitable
      experimental animal models for future investigations in this increasingly
      important area.

PMID- 1359666
TI  - Airway calibre as a confounder in interpreting bronchial responsiveness in
      asthma.
AB  - BACKGROUND: The relation between airway responsiveness to constrictor agents and
      forced expiratory volume in one second (FEV1) is important when interpreting
      change in airway responsiveness after an intervention. The aim of the study was
      to analyse the relation between FEV1 as a percentage of predicted values (%
      predicted) and airway responsiveness between and within asthmatic subjects.
      METHODS: Results of non-specific bronchial challenge tests were pooled from two
      randomised crossover studies comparing the effect of a non-sedative antihistamine
      with placebo in 35 patients with moderate asthma. The design of the two studies
      was similar: the provocative concentration of either histamine (first study) or
      methacholine (second study) resulting in a 20% decrease in ventilatory capacity
      (PC20) was repeated at two week intervals while patients were treated with the
      antihistamine or placebo. The dose of inhaled corticosteroid was gradually
      reduced during the study. Data were analysed with PC20 as the dependent variable
      in a general linear model so that the influence on PC20 of inhaled corticosteroid
      dose, antihistamine, and choice of bronchoconstricting agent could be separated
      from the influence of FEV1% predicted. RESULTS: The correlation coefficient
      between mean PC20 and mean prechallenge FEV1 for each patient was 0.45. In the
      general linear model two thirds (65%) of the variation in PC20 was due to
      variation between subjects. One third of the within subject variation in PC20
      could be explained by variation in prechallenge FEV1% predicted (a change in FEV1
      of 27% predicted was associated with one doubling or halving of PC20). Treatment
      with the antihistamine had no influence on PC20, except when histamine was used
      as the bronchoconstricting agent. The dose of inhaled corticosteroid had a small
      but significant effect. CONCLUSIONS: The variation in a patient's PC20 over time
      (several months) is related to changes in FEV1% predicted. Variation in FEV1%
      predicted explains less of the variation in bronchial responsiveness between
      subjects where a patient specific factor, which is probably related to the
      pathogenesis of bronchial asthma, seems to dominate.

PMID- 1359667
TI  - Development and evaluation of ELISAs for factor XIIIA and XIIIB subunits in
      plasma.
AB  - Severe, congenital deficiency of factor XIII is extremely rare. However, a
      moderate reduction in the plasma level of the functional subunit (factor XIIIA)
      and also to a lesser extent of the carrier subunit (factor XIIIB), and a decrease
      in the XIIIA:B subunit ratio, have recently been reported in patients with the
      inflammatory bowel disorder Crohn's disease, particularly during clinical
      relapse. In order to accurately monitor patients, sensitive, reliable assays for
      the two subunits of factor XIII are required. We report here the development and
      validation of ELISAs for these components. The assays are identical except in
      respect of the specificity of the polyclonal antiserum used as starting material,
      both of which are commercially available. The antisera are purified by n-octanoic
      acid precipitation and portions of these purified immunoglobulins are used as
      coating antibodies. The remaining portions are biotinylated and used with
      streptavidin and horse-radish peroxidase as tracer antibodies. A normal range (n
      = 24) was established for factor XIIIA (mean 95 range 60-130 U/dl) and for factor
      XIIIB (mean 99 range 60-130 U/dl). There were no significant differences between
      the ELISA and electroimmunodiffusion assays either for factor XIIIA (means +/- 1
      standard deviation 95 +/- 15.9 and 89 +/- 22.7 respectively) or for factor XIIIB
      (99 +/- 18.3 and 106 +/- 23.4 respectively). These assays have been in routine
      use for six months, during which time two further antisera purifications and
      biotinylations have been carried out without significant problems of
      reproducibility or stability.

PMID- 1359668
TI  - Canine leukocyte cell adhesion molecules (LeuCAMs): characterization of the
      CD11/CD18 family.
AB  - The canine LeuCAM (CD11/CD18) family is characterized using a panel of newly
      developed anti-canine LeuCAM monoclonal antibodies (mAb) as well as a cross
      reactive anti-human CD11b mAb. The new anti-canine LeuCAM mAb were developed by
      immunizing mice with purified canine CD11/CD18 antigen derived from an anti
      canine CD18 affinity column. Six mAb with reactivity to the canine LeuCAM family
      were cloned and characterized. These 6 included a new anti-canine CD18 mAb, 2
      anti-canine CD11a mAb, 2 anti-canine CD11c mAb, and a mAb which recognizes a
      novel canine CD11/CD18-related macrophage antigen, designated LeuCAMmac, which is
      described in a separate report. The cell and tissue distribution of canine
      LeuCAMs was found to be similar to that reported in other species with a few
      notable exceptions. One prominent exception was the finding that canine CD11c, in
      contrast to human CD11c, was much more widely distributed on dendritic cells than
      it was on tissue macrophages. The molecular organization of the canine LeuCAM
      family was also found to be similar to that reported in other species, with the
      possible exception of the canine CD11b alpha chain, which may exist as several
      different species. It is anticipated that these anti-canine LeuCAM mAb will prove
      useful in immunophenotypic studies of canine hemolymphatic system neoplasia.

PMID- 1359669
TI  - Association of HLA-B51 and lack of association of class II alleles with Behcet's
      disease.
AB  - Eighty-one Behcet's disease patients have been studied for HLA association by HLA
      DRB1, -DQA1, -DQB1 and -DPB1 genotyping with the polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) technique and for NcoI RFLP
      in the tumor-necrosis factor (TNF beta) gene by Southern hybridization in
      addition to serological typing. In serological typing, the frequency of HLA-B51
      was significantly increased in the patients. In PCR genotyping, there was a
      significant increase in the HLA-DRB1*0802, DQA1*0301 and DQB1*0303 alleles,
      whereas the frequencies of DRB1*1502, DQA1*0103, DQA1*0101, DQB1*0601 and
      DQB1*0501 showed a significant decrease in the patients. No significant
      difference was observed in any HLA-DPB1 alleles. Among them, B51 was found to be
      a genetic marker most strongly associated with Behcet's disease (p less than
      0.00005, chi 2 = 46.47, pc[corrected p] less than 0.005). The positive and
      negative associations of class II alleles with the disease can be explained by
      linkage disequilibrium with B51, and do not reach statistical significance by the
      corrected p-value test. In NcoI RFLP typing in the TNF beta gene, 250 kb
      centromeric of the HLA-B gene, the frequency of a 5.5 kb fragment was
      considerably decreased in the patients when compared to the controls, although
      the decrease was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359670
TI  - HLA-DP polymorphism in the present-day San (Bushmen) and Khoi (Hottentots) using
      polymerase chain reaction and sequence-specific oligonucleotide typing.

PMID- 1359671
TI  - HLA-DQB1 allele typing by a new PCR-RFLP method: correlation with a PCR-SSO
      method.
AB  - We have developed a new PCR-RFLP method for HLA-DQB1 typing. This method was easy
      to follow, requiring only one DQB1 generic amplification and 5 endonucleases to
      assign 14 out of 15 HLA-DQB1 alleles. In addition, we determined that by using
      one generic amplification and two enzymes (Sau96 I and Hae III) it was possible
      to type the generic specificities: DQw2, DQw4, DQw5, DQw6, and DQw7, DQw8-9,
      providing a practical alternative for serological HLA-DQ generic typing. We also
      performed a side-by-side correlation with a PCR-SSO typing method and found an
      almost 100% concordance between the methods. The limitations of these methods
      were: 1) the PCR-RFLP method did not allow the differentiation between the HLA
      DQB1*0602 and *0603 alleles; 2) the PCR-SSO method gave crosshybridization
      signals in the detection of *0302 or *0303 alleles. Our results suggested that
      both methods, PCR-RFLP and PCR-SSO, are useful alternatives for HLA-DQB1 typing.

PMID- 1359672
TI  - Studies of RFLP-inferred HLA-DR-DQ haplotypes in Danish women with recurrent
      fetal losses.
AB  - Results of HLA-DR and -DQ typing by RFLP in 152 unrelated women with at least 3
      unexplained fetal losses were compared with those of 210 normal controls. The
      overall distribution of DR-DQ phenotypes did not differ significantly between
      patients and controls. In a subgroup of 59 patients having had at least 4 fetal
      losses, a significantly higher number of patients than controls were DRw17,DQw2
      positive (RR = 2.9, pcorrected less than 0.02). DR-DQ haplotypes which carry DQB1
      alleles encoding an amino acid other than aspartic acid at codon 57 in the second
      exon (non-Asp57 haplotypes) have been reported to confer susceptibility to
      several immunologically-mediated diseases. We found that the total frequency of
      non-Asp57 haplotypes (other than DR7,DQw2 which has unique features) was
      significantly increased in patients (50.0%) compared with controls (39.3%) (p
      less than 0.005). In the total group of patients and in the group with at least 4
      fetal losses, 22.4% and 32.2% respectively were homozygous non-Asp57/non-Asp57
      compared with 13.3% among controls (RR = 1.9, p less than 0.025 and RR = 3.1, p
      less than 0.001, respectively). The results suggest that DRw17,DQw2 confers
      susceptibility to suffer recurrent fetal losses. However, it is possible that the
      HLA-associated susceptibility may be primarily conferred by DQ molecules lacking
      aspartic acid at codon 57 in the DQ beta chain.

PMID- 1359673
TI  - HLA-DPB1 typing with polymerase chain reaction and restriction fragment length
      polymorphism technique in Danes.
AB  - We have used the polymerase chain reaction (PCR) in combination with the
      restriction fragment length polymorphism (RFLP) technique for HLA-DBP1 typing.
      After PCR amplification of the polymorphic second exon of the HLA-DPB1 locus, the
      PCR product was digested with seven allele-specific restriction endonucleases:
      RsaI, FokI, ApaI, SacI, BstUI, EcoNI, and DdeI, and the DNA fragments were
      separated by electrophoresis in agarose gels. Altogether, 71 individuals were
      investigated and 16 different HLA-DPB1 types were observed in 26 different
      heterozygotic combinations, as well as five possible homozygotes. Four
      heterozygotes could not be unequivocally typed with the PCR-RFLP method. The HLA
      DPB1 typing results obtained with the PCR-RFLP method were compared with the
      typing results obtained with PCR allele-specific oligonucleotides (PCR-ASO) in 50
      individuals. The results obtained with the two methods were concordant in 84% of
      the cases. One of the HLA-DPB1 types was discrepant in six heterozygotes, both
      HLA-DPB1 types were discrepant in one heterozygote, and in one individual two HLA
      DPB1 types were identified with the PCR-RFLP technique while only one HLA-DPB1
      type could be demonstrated with the PCR-ASO technique. The frequencies of the HLA
      DPB1 genotypes deduced from the results of PCR-RFLP typing were estimated in 71
      healthy Danes.

PMID- 1359674
TI  - A mosquito neuropeptide in a moth larva (Helicoverpa zea): relation to FMRF-amide
      immunoreactivity.
AB  - The cerebral nervous and midgut endocrine systems of the larval corn earworm,
      Helicoverpa zea, were examined using light microscopy and immunocytochemistry for
      RF-amide family peptides. Immunoreactivity for a mosquito neuropeptide, Aedes
      Head Peptide-I (Aea-HP-I,pERPhPSLKTRFa), is widely distributed in this
      lepidopteran. Immunostaining for Aea-HP-I is localized (1a) in perikarya and
      axons of the brain, the subesophageal ganglion, and the first thoracic ganglion,
      (b) in peripheral axons innervating muscles of the midgut, and (2) in numerous
      midgut endocrine cells. Aea-HP-I-associated activity generally occurs as a subset
      of FMRF-amide (FMRFa; a molluscan cardioactive peptide) immunoreactivity. Cross
      reactivity studies indicate that Aea-HP-I and FMRFa immunoreactivities are
      heterogeneous in the cerebral nervous system and in axons innervating the muscles
      of the midgut, but may be homogeneous in midgut endocrine cells. Radioimmunoassay
      for Aea-HP-I reveals immunoreactivity in hemolymph, as well as in extracts of
      midguts and heads.

PMID- 1359675
TI  - Morphological alterations accompanying the effect of peptaibiotics, alpha
      aminoisobutyric acid-rich secondary metabolites of filamentous fungi, on Culex
      pipiens larvae.
AB  - The effect of different representatives of the group of peptaibiotics, alpha
      amino-isobutyric acid rich secondary metabolites of filamentous fungi, on Culex
      pipiens larvae was studied. Light and transmission electron microscopy techniques
      were used to localize the intracellular damage and to determine the target
      organells for the mode of action of peptaibols in mosquito larvae. Though
      different in insecticidal activity, all tested compounds induced the same type of
      tissue damage, which was characterized by heavy challenge of mitochondria
      followed by partial swelling, crystaeolysis and destruction of mitochondrial
      walls. It is concluded that the mode of action of peptaibols in mosquito larvae
      is mediated through the damage of mitochondria. The structure-mosquitocidal
      effect of these compounds, their potential mode of action and role in the natural
      fungal entomopathogenic process are briefly discussed.

PMID- 1359676
TI  - [Old and new alpha 2-adrenoceptor agonists. 1. Xylazine and medetomidine].
AB  - The "discovery" of alpha 2-receptors permits the explanation of the mechanism of
      xylazine that was hitherto poorly understood. The substance can be classified as
      an alpha 2-adrenoceptor agonist. In the near future two new alpha 2-adrenoceptor
      agonists will be available in Germany: medetomidine for small animals and
      detomidine for large animals. Also a new alpha 2-adrenoceptor antagonist will be
      introduced: atipamezole. alpha 2-adrenoceptor agonists cause sedation, analgesia
      and muscle relaxation. Notable side effects are bradycardia, heart block and a
      dose dependent respiratory depression. A comprehensive survey on the pharmacology
      of the alpha 2-adrenoceptor agonists is given. The previous literature is
      summarized and discussed, including own studies and clinical experience. An
      attempt is made to assess the clinical importance of the new drugs. For certain
      indications medetomidine alone may not be satisfying and combination with other
      drugs becomes necessary. If sedation is inadequate, the combination with
      benzodiazepines or propofol is advised; if analgesia is poor, the combination
      with ketamine or an opioid is recommended.

PMID- 1359677
TI  - Sertoli cells isolated from adult 2,5-hexanedione-exposed rats exhibit atypical
      morphology and actin distribution.
AB  - Sertoli cells were isolated from 2,5-hexanedione (2,5-HD)-exposed, cryptorchid
      and 21-day-old rats in order to examine alterations in in vitro Sertoli cell
      transferrin secretion, germ cell adhesion, in vitro morphology, and cytoskeletal
      organization which might be involved in the irreversibility of 2,5-HD-induced
      testicular injury. Sertoli cells isolated from 21-day-old, cryptorchid and 2,5-HD
      exposed rats exhibited similar transferrin secretion as measured using an enzyme
      linked immunosorbent assay. Germ-cell adhesion was measured using [3H]leucine
      labeled immature rat germ cells and revealed similar levels of germ-cell binding
      in Sertoli cell cultures isolated from the three groups of rats. Differential
      interference contrast microscopy demonstrated that Sertoli cells isolated from
      2,5-HD-exposed rats possessed an atypical spindle shape and long cytoplasmic
      processes. The immunofluorescent distribution of tubulin and vimentin
      corresponded with the morphological appearance of the cells with well-defined
      microtubule and intermediate filament networks which, in the cells isolated from
      2,5-HD-exposed rats, extended into the cytoplasmic processes. Rhodamine
      conjugated phalloidin-labeled actin stress fibers were decreased in density
      within the 2,5-HD-exposed rat Sertoli cells. The altered morphology and
      distribution of actin filaments within Sertoli cells isolated from adult 2,5-HD
      exposed rats may reflect an underlying insult which is involved in the
      irreversible nature of 2,5-HD intoxication.

PMID- 1359678
TI  - The effects of Indian red scorpion Buthus tamulus venom in vivo and in vitro.
AB  - The Indian red scorpion Buthus tamulus (or Mesobuthus tamulus) can cause fatal
      envenoming, but its mechanism of action is unclear. Venom was tested in vivo in
      anaesthetized rats and in vitro on isolated cardiac and skeletal muscle
      preparations. In vivo, the venom caused marked rhythmical fluctuations in blood
      pressure preceding cardiovascular collapse and death. On sheep Purkinje fibres,
      venom could induce spontaneous action potentials and cause prolongation of action
      potential duration. In chick biventer cervicis and mouse triangularis sterni
      preparations, venom enhanced the release of acetylcholine and induced repetitive
      firing of nerve action potentials in response to single shock stimulation. High
      concentrations caused stimulation then block of neuromuscular transmission. The
      main effects of Buthus tamulus venom are likely to be due to toxins that affect
      the opening of Na+ channels in nerves and muscles. This will cause an increase in
      the release of neurotransmitters in the peripheral nervous system, which may
      produce cardiovascular abnormalities and respiratory paralysis.

PMID- 1359679
TI  - Purification and characterization of iotrochotin, a novel toxin from the
      Caribbean sponge Iotrochota birotulata, which selectively permeabilizes
      synaptosomes.
AB  - A protein termed iotrochotin (IOT) was isolated from the exudate of the Caribbean
      sponge Iotrochota birotulata using as an assay its stimulation of the release of
      radioactivity from synaptosomes preloaded with [3H]choline. Sephadex G-50
      chromatography of the exudate produced one peak, with a mol. wt of approximately
      18,000, which was further resolved into two active fractions by anion exchange
      chromatography. The more tightly bound of the two fractions was characterized and
      referred to as IOT. The action of IOT was essentially complete by 0.5-1.0 min and
      was independent of the Ca2+ or Na+ content of the incubation mixture. Released
      radioactivity included about 50% each of [3H]acetylcholine and [3H]choline.
      Release of radioactivity increased as a function of IOT concentration and then
      reached a maximum. Extrapolated asymptotic release was nearly equal to that
      obtained by lysing the synaptosomes. IOT also released radioactivity from
      synaptosomes which had been preincubated with other tritiated neurotransmitters
      or with 2-[3H]deoxy-D-glucose. Lactate dehydrogenase and choline
      acetyltransferase activities were not released from synaptosomes by treatment
      with IOT, but were released by digitonin. IOT therefore releases some of the
      smaller molecular weight components of synaptosomes, but does not permeabilize
      the synaptosomal membrane in the same way as digitonin treatment.

PMID- 1359680
TI  - Phoneutria nigriventer (armed spider) venom induces increased vascular
      permeability in rat and rabbit skin in vivo.
AB  - The effect of intradermally injected Phoneutria nigriventer venom (PNV) on
      vascular permeability of both rat and rabbit skin has been investigated. Oedema
      formation was measured as the local extravascular accumulation at skin sites of
      intravenously injected 125I-human serum albumin. In both rat and rabbit PNV
      induced dose-dependent oedema which was greatly potentiated by the vasodilators
      calcitonin-gene-related peptide and prostaglandin E1. In rats, PNV-induced oedema
      was markedly reduced either by previous treatment of the animals with the
      histamine H1 antagonist mepyramine and the serotonin antagonist methysergide or
      when venom was dialysed, indicating a major role for histamine and serotonin. In
      rabbits, dialysis of the venom to remove histamine and serotonin did not reduce
      PNV-induced oedema, indicating presence of oedematogenic component(s) which are
      different from the amines histamine or serotonin.

PMID- 1359681
TI  - Role of H2-receptor antagonists in the treatment of duodenitis.
AB  - Non-erosive duodenitis is an ulcer-independent disorder, the pathogenesis of
      which is still unclear but apparently unrelated to gastric hyperacidity. However,
      antisecretory agents such as H2-blockers can be effective not only in relieving
      dyspeptic symptoms but also in promoting endoscopic healing or improvement. In
      this respect conflicting data are reported with cimetidine while promising,
      although preliminary, results were obtained with ranitidine and with nizatidine.
      Nizatidine seems especially effective when administered at a dose of 150 mg
      b.i.d., a regimen providing moderate, but continuous acid inhibition throughout a
      24 hour period.

PMID- 1359682
TI  - [Poisonings by beta-adrenoblockaders].
AB  - The review includes data on symptomatology of acute poisoning with beta
      adrenoblockers, their distribution in biological material, main pathways of
      metabolism in human body. Necessity for developing methods of systemic analysis
      of beta-adrenoblockers in biological material is pointed out.

PMID- 1359683
TI  - The reservoir of Plasmodium falciparum malaria in a holoendemic area of western
      Kenya.
AB  - The reservoir of infectious Plasmodium falciparum gametocytes in a population
      living in an area of holoendemic malaria in western Kenya was estimated by
      directly feeding mosquitoes on volunteers. Resulting mosquito infections were
      assessed both by midgut examination for oocysts and by enzyme-linked
      immunosorbent assay for P. falciparum circumsporozoite antigen. Calculations
      based on the age structure of the population and the resulting rates of mosquito
      infections indicated that children under 10 years of age were responsible for 72%
      of mosquito infections, individuals between 10 and 21 years of age contributed
      12%, and those over 21 years of age accounted for 16%. No infection resulted in
      mosquitoes fed on infants less than 1 year of age.

PMID- 1359684
TI  - The effect of donor T lymphocytes and total-body irradiation on hemopoietic
      engraftment and pulmonary toxicity following experimental allogeneic bone marrow
      transplantation.
AB  - To study the effects of donor T lymphocytes on engraftment and graft-versus-host
      disease in relation to recipient total-body irradiation, we have returned small
      numbers of T cells to T-cell-depleted bone marrow transplanted across a minor
      histocompatibility barrier in mice (B10.BR-->CBA). T-cell-depleted B10.BR marrow
      (10(7) cells) was transplanted into CBA recipients prepared with TBI doses
      ranging from 4 to 14 Gy. Selected animals also received 10(4) (0.1%) and 10(5)
      (1.0%) measured B10.BR T lymphocytes. The extent of donor marrow engraftment was
      determined from hemoglobin and carbonic anhydrase phenotyping of peripheral blood
      at 3 months posttransplant. Toxicity was assessed from breathing-rate
      measurements, histopathology, and animal survival. Addition of T cells had a
      profound effect on survival related to radiation dose. The TBI doses resulting in
      an LD50 at 12 weeks were 6.9 Gy, 9.3 Gy, and 13.0 Gy for animals receiving 10(5),
      10(4), and no T cells, respectively. Mortality was associated with pulmonary
      dysfunction as measured by an elevation of breathing rates. Autopsy and
      histological analysis revealed extensive damage to the lung parenchyma. In
      contrast to the toxicity data, addition of T cells to the donor marrow had no
      effect on the TBI dose required for equivalent erythroid engraftment. These
      results demonstrate that in combination with TBI small numbers of T cells in the
      transplanted marrow do not aid engraftment but do significantly increase the risk
      of pulmonary toxicity.

PMID- 1359685
TI  - Induction of a cell-transferable suppression of alloreactivity by photodamaged
      lymphocytes.
AB  - We have reported previously that splenocytes from BALB/c mice acutely rejecting
      CBA/j skin allografts were exposed to 8-methoxypsoralen (8-MOP) and ultraviolet A
      light and infused several times intravenously into naive BALB/c recipients; the
      recipients were hyporesponsive to CBA/j alloantigens in skin graft and delayed
      type hypersensitivity assays, as well as in mixed leukocyte culture and
      cytotoxicity assays. We currently expand on this work by showing that donor
      specific tolerance can be transferred adoptively to naive syngeneic animals via
      unfractionated splenocytes from mice rendered tolerant by the previous protocol.
      This suppressed response to alloantigen was transferred optimally with
      splenocytes taken from mice on the sixth day after the final treatment with PET
      cells. We further demonstrate that the cells that are adoptively transferring
      suppression are radiosensitive, Thy-1+, Lyt-2+, L3T4- T lymphocytes.

PMID- 1359687
TI  - [X National Reunion of Experimental and Clinical Oncology. Pordenone, 4-7
      November 1992. Abstracts].

PMID- 1359686
TI  - P-glycoprotein but not topoisomerase II and glutathione-S-transferase-pi accounts
      for enhanced intracellular drug-resistance in LoVo MDR human cell lines.
AB  - The biochemical bases of the multidrug-resistant (MDR) phenotype were
      investigated in drug-resistant sublines derived from LoVo human colon carcinoma
      cell lines by doxorubicin (DOX) and teniposide (VM26) selection. In addition to P
      glycoprotein-mediated drug extrusion through the plasma-membrane, LoVo MDR cells
      display a further drug-resistance mechanism. That is, to achieve equitoxic
      effects, LoVo MDR sublines require much higher intracellular drug concentrations
      than those required by LoVo drug-sensitive parent cell line. Involvement of mdr1,
      topoisomerase II and glutathione-S-transferase-pi (GST-pi) drug-resistance
      systems in intracellular drug resistance was investigated. Pharmacologic and
      biochemical data indicated that intracellular drug resistance in LoVo MDR
      sublines is uniquely consequent to the drug-transporting property of
      intracytoplasmic membrane-bound P-glycoprotein molecules which compartment drugs
      in vacuole-like structures.

PMID- 1359688
TI  - Neuroendocrine carcinoma of the stomach with extensive somatostatin
      immunoreactivity.
AB  - Upper gastrointestinal tract neuroendocrine tumors producing predominantly
      somatostatin have thus far been described only in the duodenum; their
      characteristic features include the frequent presence of psammoma bodies
      (psammomatous somatostinomas), and the association with von Recklinghausen's
      neurofibromatosis. Gastric neuroendocrine tumors, on the other hand, tend to
      display immunoreactivity to serotonin but may include small subpopulations
      producing gastrin, motilin, pancreatic polypeptide, and somatostatin. In this
      report we describe a neuroendocrine carcinoma of the stomach with rapidly fatal
      outcome, displaying neurosecretory granules by electron microscopy and
      immunoreactivity to pan-neuroendocrine markers, ie, chromogranin and neuron
      specific enolase. The only neuroendocrine regulatory peptide detected in the
      tumor was somatostatin, identified by immunohistochemistry in the majority of
      neoplastic cells. In contrast with duodenal somatostinomas, there were no
      psammoma bodies and no demonstrable association with von Recklinghausen's
      neurofibromatosis. To our knowledge this appears to be the first report of a
      malignant neuroendocrine tumor with diffuse somatostatin immunoreactivity.

PMID- 1359689
TI  - [Distal pedicled musculus extensor digitorum brevis island flap for covering an
      amputation stump--case report].

PMID- 1359691
TI  - Occurrence and enterotoxigenicity of F17 fimbriae bearing Escherichia coli from
      calf diarrhoea.

PMID- 1359690
TI  - Bovine haemorrhagic colitis associated with CNF+ and F6+ (987P) E coli.

PMID- 1359692
TI  - Colonization factor different from K88, K99, F41 and 987P in enterotoxigenic
      Escherichia coli strains isolated from postweaning diarrhoea in pigs.
AB  - A novel common colonization factor was detected in enterotoxigenic strains of
      Escherichia coli isolated from intestinal contents of piglets affected with
      postweaning diarrhoea. This factor was antigenically distinct from the previously
      described K88, K99, F41, 987P, CFAI, CFAII and Att25 fimbrial antigens. E. coli
      strains possessing this factor adhered to the pig intestinal brush borders and
      one strain, used in experimental infection in weanlings, colonized the intestinal
      epithelium and induced diarrhoea. Examination of 212 toxigenic strains of E. coli
      isolated from weanlings revealed the presence of the novel common colonization
      factor in 83 strains, belonging to serogroups O25, O108, O138, O141, O147 and
      O157. The antigen K88 was detected in 47 strains belonging to serogroups O8,
      O141, O147 and O149.

PMID- 1359693
TI  - The protective efficacy of pili from different strains of Moraxella bovis within
      the same serogroup against infectious bovine keratoconjunctivitis.
AB  - Three groups of ten calves were each immunised with a total of 400 micrograms
      pili prepared from three separate strains of Moraxella bovis in Alhydrogel-oil
      adjuvant as two divided, equal doses 21 days apart. Groups 1 and 2 each received
      a monovalent vaccine made from strain 4L and S276R respectively, which belonged
      to pili serogroup A. Group 3 received vaccine made from pili of strain Maff1,
      belonging to serogroup F. A further group of ten calves served as non-vaccinated
      controls. Calves in groups 1 and 2 had developed serogroup A-specific antibody
      and those in group 3 developed serogroup F-specific antibody, and some evidence
      of cross-reacting antibody was also detected when measured by an agglutination
      test using formalin-killed piliated cells of serogroup A strain 4L. Although
      antibody titres measured against purified pili by ELISA were highest with
      homologous serogroup antigens, cross-reactive titres to shared epitopes of M.
      bovis pili were also detected by this method. Ocular challenge of the 40 calves
      with virulent M. bovis of serogroup A strain S276R was carried out 14 days after
      the second vaccine dose. All non-vaccinated calves developed infectious bovine
      keratoconjunctivitis (IBK). The percentage protection in groups 1 (strain 4L) and
      2 (strain S276R) was 60% and 80% respectively (P less than 0.05), with mean
      lesion scores of 0.7 and 0.3 out of a possible 6.0. The percentage protection of
      calves in group 3 (strain Maff1) was only 30%, with a mean lesion score of 1.4
      compared with 2.2 for non-vaccinated controls. The present findings, together
      with other evidence indicating that immunity to IBK is serogroup-specific,
      suggest that inclusion of pili from one representative strain from each of the
      seven Australian and British serogroups in a polyvalent, subunit vaccine should
      effectively protect the majority of cattle against IBK caused by most field
      strains of M. bovis encountered in Australia and the United Kingdom.

PMID- 1359694
TI  - Peroxisomes in human colon carcinomas. A cytochemical and biochemical study.
AB  - The presence of peroxisomes and their enzymic content were investigated and
      compared in healthy and neoplastic human colon epithelial cells using
      cytochemical studies at the ultrastructural level as well as biochemical
      analyses. Catalase-positive organelles were found to be more numerous in normal
      than in colonic neoplastic cells. Biochemical assays revealed that no D-aminoacid
      oxidase or L-alpha-hydroxyacid oxidase activity was detected in normal or tumor
      tissues. The specific activities of catalase, fatty-acyl CoA oxidase and enoyl
      CoA hydratase/3 hydroxyacyl-CoA dehydrogenase (the so-called peroxisomal
      bifunctional enzyme of the beta-oxidation system) were found to be diminished in
      carcinoma cells compared with the control tissue. The fall in catalase activity
      correlated well with tumor stage according to Dukes, suggesting that this
      peroxisomal enzyme could be used as a potential prognostic marker.

PMID- 1359695
TI  - Influence of synovial cells on cartilage in vitro: induction of breakdown and
      inhibition of synthesis.
AB  - Organoid or high density cultures of: (1) synovial cells from patients with
      rheumatoid arthritis, and (2) prechondrogenic mesenchymal cells from limb buds of
      12-day-old mouse embryos, were co-cultured for 7-10 days using the Trowell
      culture system. Depending on the time of commencing co-cultivation,
      chondrogenesis was inhibited (co-cultivation from the start) or the cartilaginous
      matrix was partly degraded (co-cultivation after formation of embryonic
      cartilage, i.e. on day 4). These effects were obtained with cells from synovial
      fluid as well as from synovial tissue. Matrix degradation and the behaviour of
      the different cell types could be demonstrated well by electron microscopy under
      the in vitro conditions applied.

PMID- 1359696
TI  - Tissue distribution of neutrophils in postischemic acute renal failure.
AB  - Polymorphonuclear neutrophil granulocytes (PMNs) seem to participate in the
      pathogenesis of renal ischemic reperfusion injury. The kidneys from male Sprague
      Dawley rats were immersion-fixed after 45 min of renal artery clamping followed
      by reperfusion for 0, 5, 20, and 120 min, respectively. The tissue distribution
      of PMNs in the kidneys was studied histochemically using naphthol AS-D
      chloroacetate esterase as a specific marker for these cells. Neutrophil counts
      per unit sectional area were obtained for renal cortex, outer and inner medulla.
      In the cortex separate intraglomerular and peritubular counts, and in the outer
      medulla separate outer and inner stripe counts were made. After 120 min of
      reperfusion the total renal PMN counts were 488 +/- 62 (n = 4) compared with 54
      +/- 4 (n = 4) per cm2 in nonischemic controls. Within 120 min of reperfusion PMN
      counts increased by a factor of 8 in the cortex, of 12 in the outer medulla and
      of 14 in the inner medulla, compared with controls. The ratio of intraglomerular
      against peritubular PMN counts was approximately 2 in controls, but 0.5 after a
      120-min reperfusion interval. The outer stripe of the outer medulla contained
      only a small number of PMNs whereas PMN counts of 923 +/- 197 (n = 4) per cm2
      were found in the inner stripe after 120 min reperfusion. Interestingly, there
      was a marked increase in PMNs in the inner stripe during the first 5 min of
      reperfusion but no extravasation of PMNs was observed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1359697
TI  - Intraperitoneal amyloid formation by amyloid enhancing factor--rich macrophages
      in ascitic fluid.
AB  - Although resident peritoneal cells from amyloidotic mice (amyloidotic peritoneal
      cells) are capable of processing the precursor protein of secondary amyloidosis,
      serum amyloid A (SAA) to amyloid fibrils, the peritoneum is a rare site for
      amyloid deposition. This is considered to be due to a deficiency of SAA in the
      peritoneum. To increase the supply of SAA to the peritoneum, ascitic fluid
      containing about the same protein constituents as in the serum was induced in
      mice. Amyloidotic peritoneal cells were packed in a microchamber which was
      shielded with filter membranes, and cultured in ascitic fluid supplemented with
      additional inflammatory factors. On the 7th day, Congo red-positive structures
      which showed green birefringence under polarized light were found inside and
      occasionally outside the chamber. By anti-AA or -SAA immunostaining, amyloid
      deposits and the cell surfaces of macrophages were positive. Immunologic
      depletion of T- and B-lymphocytes from the amyloidotic peritoneal cells did not
      adversely effect the amyloid formation in microchambers. These results suggest
      that either ascitic fluid containing sufficient amounts of SAA, or peritoneal
      macrophages with a high amyloid enhancing factor (AEF) activity are indispensable
      for AA amyloid fibrillogenesis in the peritoneum.

PMID- 1359698
TI  - Altered transferrin gene expression in preneoplastic and neoplastic liver lesions
      induced in rats with N-nitrosomorpholine.
AB  - The expression of the gene for the iron transport protein transferrin was found
      to be altered in preneoplastic and neoplastic lesions induced in the rat liver by
      N-nitrosomorpholine. The total RNA of ten hepatocellular carcinomas (HCC) was
      investigated by Northern blot analysis using a cDNA-probe comprising 150 bp of
      the 3' region and compared with the total hepatic RNA in untreated rats. Seven
      hepatocellular carcinomas showed slight or pronounced reduction in transferrin
      expression. In situ hybridization of two additional hepatocellular carcinomas
      revealed marked reduction in the mRNA level for the transferrin gene compared
      with the surrounding tissue. In contrast, the majority of early preneoplastic
      lesions storing excess glycogen and tigroid cell foci expressed increased levels
      of transferrin mRNA. The loss of glycogen in mixed cell foci, which represent a
      later stage of hepatocarcinogenesis, was usually accompanied by a decrease in
      transferrin mRNA suggesting a close relationship between this change in gene
      expression and cellular dedifferentiation emerging during hepatocarcinogenesis.

PMID- 1359699
TI  - Immunohistological study of skin involvement in Kikuchi's disease.
AB  - Five patients with histiocytic necrotizing lymphadenitis (Kikuchi's disease) with
      erythematous or popular skin lesions were studied. All patients healed naturally
      within a few months like the patients with no skin involvement. Histological
      findings for the skin lesions mimicked cutaneous malignant lymphoma. The
      infiltrated mononuclear cells usually demonstrated positive reactions for Ki-M1p
      (20-63%), lysozymes (13-54%), MT-1 (18-64%), UCHL-1 (22-39%) and LN2 (17-36%).
      OPD-4 and L26 positive cells were few in number. These results suggest that the
      infiltrated cells in a Kikuchi's disease skin lesion are composed of the same
      components as the affected lesion in the lymph node.

PMID- 1359700
TI  - Low incidence of bronchus-associated lymphoid tissue (BALT) in chronically
      inflamed human lungs.
AB  - The relevance of bronchus-associated lymphoid tissue (BALT) in man is still under
      discussion. Animal experiments indicate that the development of BALT is dependent
      on microbial stimulation. Therefore, the incidence of BALT was investigated
      retrospectively in specimens removed during surgical procedures on patients with
      chronic pulmonary inflammation. All these patients had severe chronic bronchitis
      and bronchiectasis, but BALT was found in only 8%. In patients with BALT and a
      malignant tumor, occlusion of a bronchus with poststenotic pneumonia was always
      present and BALT was observed exclusively in areas peripheral to the occlusion.
      In man other compartments of the lung must be responsible for the immune function
      of BALT found in animals.

PMID- 1359701
TI  - Analysis of proliferative activity in colorectal mucosa by immunohistochemical
      detection of proliferating cell nuclear antigen (PCNA). Methodological aspects
      and application to routine diagnostic material.
AB  - Immunohistochemical detection of proliferating cell nuclear antigen (PCNA) has
      been suggested as a new approach for determining proliferative activity in
      paraffin-embedded tissue. In a prospective study PCNA immunostaining was
      performed in 284 colorectal biopsies using monoclonal antibodies 19F4 (Ogata et
      al. 1987) and PC10 (Waseem and Lane 1990) and compared with the Ki67 method. From
      each site three biopsies were taken and a variety of fixation regimens for frozen
      and paraffin-embedded samples tested. For frozen biopsies methanol fixation at 
      20 degrees C proved best. In paraffin sections PCNA could be detected after
      methacarn fixation as well as after controled fixation at 4 degrees C in 4%
      paraformaldehyde for 1 h and in most biopsies routinely fixed with 10% formalin.
      However, the latter fixation regimens revealed additional PCNA-positive cells in
      the normal superficial colonic mucosal epithelium. Although the percentage of
      cells positive for PCNA was generally lower than for Ki67, the rates correlated
      in a highly significant fashion, both in frozen methanol-fixed biopsies, and in
      paraformaldehyde-fixed paraffin-embedded samples. PCNA immunohistochemistry
      revealed a similar proliferative activity in different parts of the large bowel.
      A higher proliferative activity was found in inflamed mucosa, adenomas,
      carcinomas and even in normal mucosa from patients with colorectal neoplasms. In
      routinely fixed biopsies, the monoclonal antibody PC10 was superior to 19F4
      because of considerably less background staining. However, in the routine
      material only a rough estimate of the proliferative activity was possible by PCNA
      immunohistochemistry using these antibodies, because unpredictable numbers of non
      S-phase cells were also stained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359703
TI  - Interphasic nucleolar organizer regions expression and cell kinetics evaluation
      during gastric carcinogenesis induced by nitrosoguanidine in the rat.
AB  - An increased number of interphasic nucleolar organizer regions containing
      ribosomal cistrons associated with argyrophilic proteins (AgNORs) has been
      described in human malignant tumor cells. In this study variations in AgNOR
      numbers have been compared with changes of cell kinetics, evaluated by the
      mitotic count (MC) and bromodeoxyuridine labeling index (BrdU LI), during gastric
      carcinogenesis induced with N-methyl-N'-nitro-N-nitrosoguanidine (NG) in rats.
      Significant differences (2 P < 0.005) in AgNOR mean numbers, evaluated in the
      antral isthmic cells, in MC mean values and BrdU LI, evaluated in the whole
      antral cellular population, were found when comparing areas of acute gastritis,
      atrophy and hyperplasia in NG-treated rats with the normal mucosa in controls. No
      differences were observed in MC and BrdU LI between normal antrum and carcinoma
      cells which showed an AgNORs mean number lower than in the isthmic cells of
      controls (2 P < 0.005). Moreover, significant correlations were found comparing
      changes in AgNOR numbers with MC (r = 0.89, P < 0.001) and BrdU LI (r = 0.66, P <
      0.001) in different lesions. These data show that evaluation of AgNOR numbers
      does not allow the identification of malignant cells in NG-induced gastric
      carcinoma. However AgNOR quantification seems to be a reliable index of cell
      kinetics and related well with the cellular dividing fraction.

PMID- 1359702
TI  - Pituitary lactotrophs and somatotrophs in pregnancy: a correlative in situ
      hybridization and immunocytochemical study.
AB  - Lactotroph hyperplasia is a prominent finding in the adenohypophyses of pregnant
      women. In order to elucidate the morphogenesis of this change, pituitaries from
      16 women in various phases of pregnancy were collected at autopsy and studied by
      histology, immunocytochemistry and in situ hybridization. The results showed that
      the increase in the amount of prolactin (PRL) mRNA paralleled the progressive
      lactotroph hyperplasia. The presence of mitoses in PRL-immunoreactive cells
      provided evidence that proliferation of preexisting lactotrophs contribute to
      lactotroph accumulation. Growth hormone (GH) immunoreactive cells showed a marked
      reduction in GH mRNA indicating that GH synthesis was inhibited. In many GH
      immunoreactive cells, PRL mRNA became apparent. These findings demonstrate that
      GH is stored following discontinuation of GH synthesis. It appears that, when PRL
      is secreted in excess during pregnancy, somatotrophs are recruited to produce
      PRL. These somatotrophs begin to express PRL mRNA, transform to bihormonal
      mammosomatotrophs and possibly later to lactotrophs, contributing to PRL
      production. Mature somatotrophs may be regarded as reserve cells in the
      adenohypophysis, having the potential to switch hormone synthesis and to convert
      to mammosomatotrophs and possibly lactotrophs.

PMID- 1359704
TI  - NCI-H716 cells as a model for endocrine differentiation in colorectal cancer.
AB  - In colonic neoplasms, endocrine differentiation is encountered not only in
      carcinoid tumors but also in adenocarcinomas, where endocrine cells may represent
      a distinct line of differentiation in the tumor. The significance of endocrine
      differentiation in colorectal cancer is not well established, partly because of
      the paucity of tumor cell lines which can serve as a model for studying endocrine
      differentiation. In this report we describe the properties of NCI-H716 cells, a
      cell line derived from a poorly differentiated adenocarcinoma of the caecum,
      under various in vitro conditions and as xenografts in athymic mice. Phenotypical
      properties were immunohistochemically assessed using a panel of differentiation
      related antibodies, and also by Northern blot analysis and by electron
      microscopy. Receptors for biogenic amines and peptide hormones were analyzed by
      ligand binding assay. These studies show that: 1. NCI-H716 cells can be
      undifferentiated, or show endocrine, mucin-producing or "amphicrine" properties.
      2. Endocrine differentiation of NCI-H716 cells preferentially occurs in
      xenografts in athymic mice, which suggests that mesenchymal elements induce
      endocrine differentiation. 3. NCI-H716 cells express large amounts of high
      affinity receptors for gastrin, serotonin and somatostatin and these substances
      can regulate growth. Thus, NCI-H716 cells form a suitable model for the study of
      endocrine differentiation in intestinal epithelium and of auto- or paracrine
      growth regulation in intestinal neoplasia.

PMID- 1359706
TI  - [Outstanding theoretician and organizer of medical support for the troops (based
      on materials from the scientific conference on the centenary of the birth of B.
      K. Leonardov)].

PMID- 1359705
TI  - [A trial of the pharmacological correction of sleep disorders in sailors during a
      cruise].
AB  - The article makes a comparative estimation of the efficiency between the
      benzodiazepine pharmacological group (selenium, diazepam) and adaptogens of the
      plant origin (Extractum Leuzeae carthamoidis fluidum) for correction of sleeping
      disorders in seamen during cruise. The application of elenium and diazepam have
      caused the unpleasant subjective sensations, such as psychoemotional retardation,
      sluggishness, apathism and headaches. After application of Extractum Leuzeae
      there were no side effects like a drug hang-over; the health status, functional
      state and job performance of seamen were improved. Having taken Extractum Leuzeae
      the seamen had the normalization of sleeping in 5-7 days.

PMID- 1359707
TI  - [Effect of physiologically active polymers on the activity and hormonal induction
      of tyrosine aminotransferase].
AB  - Effect of neutral polymers on activity of tyrosine aminotransferase and
      hydrocortisone induction of the enzyme were studied. Physiologically active
      polymers decreased in most cases the basal rate of the enzymatic activity.
      Preadministration of polymers decreased hormonal induction of tyrosine
      aminotransferase. Simultaneous administration of polymers and hydrocortisone led
      to augmented and long-term induction, which appears to occur due to complex
      formation of the polymer and hormone. Gradual liberation of hydrocortisone from
      the complex enabled to maintain the hormone effective concentration for a long
      time.

PMID- 1359708
TI  - Applications of the polymerase chain reaction to HLA class II typing.

PMID- 1359709
TI  - [The characteristics of the pharmacotherapy for patients with ischemic heart
      disease and hypertension in relation to age].
AB  - On the basis of literary and own findings the authors discuss disputable problems
      of the pharmacotherapy of ischemic heart disease and hypertensive disease in the
      age aspect including patients over 60 years of age. Approaches are analyzed to
      individual choice of adequate pharmacotherapy, criteria of selection and dosages
      with special emphasis of adreno-beta-blockaders and calcium antagonists as well
      as criteria of evaluation of pharmacotherapy.

PMID- 1359710
TI  - [A method for the permanent maintainance aurotherapy of rheumatoid arthritis
      patients under the control of gold excretion].
AB  - A study is presented of 34 patients with rheumatoid arthritis. The authors
      propose a method of persistently maintained aurotherapy of patients with
      rheumatoid arthritis directed to prevention of recurrences and toxic effect of
      gold due to chrysanol treatment, the active substance of which is metallic gold.
      After course treatment with chrysanol (850-1020 mg) persistent treatment by
      maintained doses is instituted. RESULTS: prevention of recurrences of the disease
      and prevention of side effects due to the toxicity of cumulated gold.

PMID- 1359711
TI  - [Dysfunction of the diffuse neuroendocrine system as one of the possible
      pathogenetic mechanisms in bronchial asthma].

PMID- 1359714
TI  - [13th Symposium for Attorneys and Physicians. Berlin, 11-12 January 1991. Theme:
      Expert assessment in forensic psychiatry, geriatric psychiatry].

PMID- 1359712
TI  - [The disposition of natural foci of hemorrhagic fever with renal syndrome in
      different landscape areas of Tyumen Province].
AB  - Lungs of 3159 animals of the forest complex from 90 areas of 30 administrative
      districts of Tyumen Province were examined by enzyme immunoassays for antigen of
      hemorrhagic fever with renal syndrome (HFRS) during 5 years, 1985-1989. The
      antigen of HERS virus was detected in the lungs of mammals of 8 species:
      Clethrionomys glareolus and Cl. rutilus, Siberian and Arctic lemmings (first
      findings in the world), M. oeconomus, field mouse, common and pygmy shrews.
      Nearly all the findings refer to the subzone of southern taiga and adjacent areas
      of subtaiga subzone where Cl. glareolus is the main reservoir of infection and
      Cl. rutilus an additional one. In the tundra zone, Siberian lemming is the main
      reservoir of infection and Arctic lemming an additional one. No natural foci of
      HFRS were found in forest steppe and forest tundra zones. In the subzone of the
      northern and middle taiga, the antigen was found only on 4 occasions: 3 in common
      shrews and one in Cl. glareolus (near the town of Khanty-Mansisk). An irregular
      annual infection rate with HFRS virus was observed in Cl. glareolus as well as
      its decline from spring to autumn. It cannot be ruled out that lemmings are
      carriers of a distinct HFRS virus serotype.

PMID- 1359713
TI  - Special issue: Papers from the 3rd North American Regional Meeting of ISSX. San
      Diego, October 1990.

PMID- 1359715
TI  - [Expert assessment in civil rights. Determination of informed consent--from the
      physicians viewpoint].

PMID- 1359716
TI  - [The question of amino acid isomerization in the microwave field. Results of a
      model study with standard solutions].
AB  - Aqueous standard-solutions of L-alanine, L-glutamic acid, and L-proline do not
      reveal any increase of D-enantiomers after 30 min heating--neither by the
      conventional method on a hotplate, nor in a standard microwave oven. A specific
      "microwave effect" and, hence, a special consumer risk is, in contrast to recent
      assumptions, not detectable. Effects on the amino acids which were observed in
      conventionally heated samples are explained by higher heat-exposure during the
      treatment of these samples.

PMID- 1359717
TI  - [Drug therapy of peptic ulcer in the elderly].
AB  - Medical therapy of peptic ulcers in elderly patients should depend on drugs which
      have to be administered only once daily. In addition, the ideal compound should
      have minimal side effects as well as minimal, if any, interactions with
      concomitant forms of therapy. From this point of view, acid-inhibitory drugs are
      preferable to other anti-ulcer drugs, the latter having little importance in
      advanced age. For ulcer healing, the proton pump inhibitor omeprazole is
      recommended, whereas H2-blockers (predominantly ranitidine) are the first choice
      in long-term therapy in order to prevent relapses. Treatments directed towards
      eradication of Helicobacter pylori should be regarded with great caution in the
      elderly at the present time.

PMID- 1359719
TI  - [Pharmacology of excitatory amino acid receptors].
AB  - L-Glutamate is an excitatory neurotransmitter at many synapses in the animal, and
      causes neuronal damage in the mammalian neuron. Glutamate receptors have been
      classified into at least five types: NMDA-, kainate-, AMPA-, and L-AP4-type
      ionotropic receptors and metabotropic glutamate receptors. Recently new glutamate
      agonists have been introduced into the pharmacological study in neuroscience
      research. They are methoxyphenylkainoids, acromelic acids and 2
      (carboxycyclopropyl)glycine (CCG). A methoxyphenylkainoid and acromelic acid A
      are one of the most potent excitants in the mammalian central neuron. These
      compounds should provide valuable pharmacological probes for analysis of
      functions of excitatory amino acids.

PMID- 1359718
TI  - [Validation of the Child Speech Test using the Heidelberg Speech Development Test
      with six-year-old preschool children].
AB  - We present and discuss results from researches to validate a new test for
      diagnosing speech-competences of preschool children KISTE. 41 children (6;0-6;11)
      were tested both with KISTE and HSET. Correlations, factor- and clusteranalysis
      showed that the structure of both tests is different and that KISTE has a good
      differential validity for both aspects of speech: communicative and structural.

PMID- 1359720
TI  - [The intensity of the immune response to the hemorrhagic fever with renal
      syndrome virus among different population groups of Bashkortostan].
AB  - For the first time the natural immune stratum to hemorrhagic fever with the renal
      syndrome (HFRS) among the population of all regions of Bashkiria, a large
      territory with the highest morbidity level in this infection in the USSR, was
      studied. 9,176 persons over 15 years of age were examined by radioimmune
      techniques. Analysis of the immune structure of the population revealed that the
      share of immune males was higher than that of immune females, but the difference
      was less than the difference between males and females among the registered HFRS
      patients. Among children immune persons were almost completely absent. The immune
      stratum increased rather slowly among persons under 40 years, and only from this
      age the considerable increase of the immune stratum was observed (up to 16.2%).
      High risk groups included persons of such professions as forestry workers, truck
      and tractor drivers, oil workers and prospectors, livestock breeders, builders.
      These data may be used for the formation of groups to be vaccinated against HFRS
      in foci with different degrees of activity. Before vaccination the correction of
      groups to be vaccinated in a given region should be carried out, taking into
      account the immune structure of the population and the specific features of the
      local landscape and economy.

PMID- 1359721
TI  - [Factors affecting the process of the recurrence of schizophrenia (a review)].

PMID- 1359722
TI  - [The use of the bromocriptine test in schizophrenia patients resistant to
      neuroleptic therapy].
AB  - To choose differentiated therapy, 62 patients suffering from refractory
      schizophrenia were administered bromocriptine in a dose of 7.5-15 mg/day after
      they had been placed on placebo. According to the bromocriptine test, the
      treatment was changed in 53 patients. After the occurrence of the picture of
      hallucinatory stupor remission was attained with the aid of less doses of
      neuroleptics given before. In patients who responded to bromocriptine by anxious
      excitation, the health status noticeably improved after administration of
      anxiolytics and lithium carbonate. Those patients in whom bromocriptine
      eliminated psychosis were treated later with the drugs belonging to the group of
      monosubstituted benzamides.

PMID- 1359724
TI  - Future research in epileptology. Proceedings of the Harry Meinardi Congress 1992.

PMID- 1359723
TI  - Attenuated ventilatory response to hypoxaemia at vecuronium-induced partial
      neuromuscular block.
AB  - The effect of a partial neuromuscular block on the ventilatory response to
      hypercarbia and to hypoxaemia was studied in 11 non-anaesthetized male subjects.
      Respiratory frequency, tidal volume, minute volume, respiratory timing and drive
      were measured during air breathing and during stimulation by hypercarbia and
      hypoxaemia. The ventilatory response was defined as the ratio between,
      respectively, tidal volume and minute volume during ventilation stimulated by
      hypercarbia and hypoxaemia compared to measurements during air breathing. The
      ventilatory measurements were repeated on three separate occasions: before
      neuromuscular block was established, during an infusion of vecuronium aiming at a
      mechanical adductor pollicis train-of-four (TOF) ratio of 0.70, and after the
      infusion had been stopped and the neuromuscular block had spontaneously recovered
      to a TOF ratio of > 0.90. Resting ventilation during air breathing remained with
      minor variations throughout the experiment. The ventilatory response to
      hypercarbia was not affected at a TOF ratio of 0.70 as compared to measurements
      before vecuronium and at a TOF ratio of > 0.90. In contrast, the ventilatory
      response to hypoxaemia was markedly reduced at a TOF ratio of 0.70. We conclude
      that a mechanical TOF ratio of 0.70 following vecuronium may be associated with
      an inadequate ventilatory response to hypoxaemia.

PMID- 1359726
TI  - Ophthalmic Ultrasound. Conference report. Copenhagen, September 1991.

PMID- 1359727
TI  - Doppler sonographic pulse curve analysis for estimation of the haemodynamic
      function.
AB  - Experience with Doppler sonographic pulse curve analysis is given from 40
      glaucoma patients (examination of the temporal posterior ciliary artery), and
      from premature babies (blood flow in the anterior cerebral artery). In the latter
      group the reaction to pain and stress connected with blood sampling was studied.
      In the glaucoma patients focus was on the influence of IOP level on vascular
      autoregulation, and the possible response to therapy with beta-blockers.
      Describing an averaging technique, methodological problems are discussed as
      relevant for the detection of changes in flow and velocity in small blood
      vessels.

PMID- 1359725
TI  - Creutzfeldt-Jakob disease with codon 129 polymorphism (valine): a comparative
      study of patients with codon 102 point mutation or without mutations.
AB  - We examined 7 patients with Creutzfeldt-Jakob disease (CJD) with a methionine-to
      valine change at prion protein (PrP) codon 129 (CJD129 patients). These CJD129
      patients did not have either a codon 117 or 198 point mutation. For comparison,
      we also examined 7 patients with Gerstmann-Straussler syndrome (GSS) with a
      proline-to-leucine change at PrP codon 102 (GSS102 patients) and 13 patients
      without any known mutations at codons 102, 117, 129, 178, or 200 (CJDwild
      patients). CJD129 patients had a long clinical duration and ataxia at onset, but
      rarely had any periodic synchronous discharge in their electroencephalogram.
      Unlike CJDwild patients, all CJD129 patients have typical congophilic PrP plaques
      in their brain. These clinicopathological findings were similar to those of
      GSS102. However, the distribution and morphology of PrP deposits revealed by
      immunohistochemistry were different between CJD129 and GSS102. In GSS102 more
      numerous and various types of PrP plaques are seen throughout the brain, while in
      CJD129 patients a unicentric core was the major feature of PrP plaques. The
      change in codon 129 influences the clinical course and pathological findings in
      CJD.

PMID- 1359728
TI  - The statoconial membrane of the guinea pig utricular macula. Scanning electron
      microscopic investigation combined with the freeze-fracturing technique.
AB  - The superstructure of the guinea pig utricular macula was investigated using
      scanning electron microscopy combined with the freeze-fracturing technique. The
      statoconial membrane was composed of the otoconial layer, otolithic membrane and
      subcupular meshwork. The otolithic membrane consisted of closely arranged
      filaments with beaded appearance and densely packed globular matrix near the
      otoconial layer. The subcupular meshwork consisted of long branching filaments
      cross-bridged to one another. The filaments were continuous with those of the
      otolithic membrane on one side and with the surface of the epithelium on the
      other, which fills the space between the otolithic membrane and the macular
      surface. The otolithic membrane would function as a rigid plate and equally
      distribute the shear force of the otoconial layer to all the ciliary bundles. The
      subcupular meshwork may play an important role in transmitting the shear strain
      of the otolithic membrane to all the ciliary bundles and may also exert an
      additional dampening effect to prevent unwanted vibration.

PMID- 1359729
TI  - [Synthesis, analgesic activity and structure-activity relationship of 4-N
      propionyl analogs of cis-3-methyl fentanyl].
AB  - The synthesis of some 4-N-propionyl analogs of cis-3-methyl fentanyl by acyl
      chloride method. anhydride method, mixed anhydride method and DCC method is
      reported. The ethyl group in 4-N-propionyl portion of cis-3-methyl fentanyl was
      substituted by some groups with different electronic property. In mouse hot plate
      test, all compounds showed typical morphine-like action with analgesic potency
      corresponding to 49-1963 times that of morphine. Compound 3 was found to exhibit
      higher analgesic activity than cis-3-methyl fentanyl. Semiempirical INDO
      calculations have been undertaken for 4 typical compounds and it was found that
      as a result of introduction of chlorovinyl, compound 3 exhibited characteristics
      of electronic structure different from that of cis-3-methyl fentanyl. The
      relationships between analgesic activity and the electronic structure of these
      compounds were discussed.

PMID- 1359730
TI  - Effects of picroliv, the active principle of Picrorhiza kurroa, on biochemical
      changes in rat liver poisoned by Amanita phalloides.
AB  - The efficacy of Picroliv, a standardized iridoid glycoside fraction of Picrorhiza
      kurroa, was studied against the Amanita phalloides-induced biochemical changes in
      rat liver. A phalloides (50 mg.kg-1) caused significant increases in the
      activities of hepatic 5'-nucleotidase, gamma-glutamyl transpeptidase, acid
      ribonuclease, and succinate dehydrogenase, but a decrease in glucose-6
      phosphatase. The level of cytochrome P-450 in microsomal fraction and content of
      glycogen in liver showed significant depletions. Picroliv (25 mg.kg-1.d-1 x 10 d)
      provided significant restorations of all the biochemical changes poisoned by A
      phalloides except cytochrome P-450 and glycogen. These results demonstrated the
      protective effect of Picroliv against A phalloides-induced hepatotoxicity in
      rats.

PMID- 1359732
TI  - XX Nordic Congress of Physiology and Pharmacology. Copenhagen, August 16-19,
      1992. Abstracts.

PMID- 1359731
TI  - [Teratologic studies of methyl 5-aminosalicylate and salicylazopyridine].
AB  - Methyl 5-aminosalicylate hydrochloride (M-5-AS) at the dosages of 21, 42, 209,
      and 417 mg.kg-1.d-1 ig to mice during d 6-15 of pregnancy, no obvious effects on
      the placenta, fetus weight, sex differentiation, external appearance, visceral,
      and skeletal development were observed. In rats ig M-5-AS 56 and 556 mg.kg-1.d-1
      produced no noticeable effects on the organogenesis or teratogenesis either. In
      mice and rats ig salicylazopyridine 410 and 1089 mg.kg-1.d-1 respectively no
      obvious teratogenicity was detected. However, aspirin 250 mg.kg-1.d-1 ig did
      bring about significant teratogenicity in rats.

PMID- 1359733
TI  - Adrenergic and non-adrenergic cardiovascular effects of thyrotropin-releasing
      hormone (TRH) in the anaesthetized rabbit.
AB  - The effects of thyrotropin-releasing hormone (TRH) on regional blood flows were
      studied in urethane-anaesthetized rabbits. Experiments were performed both with
      and without adrenergic antagonist pretreatment. The tracer microsphere method was
      used to measure blood flow. TRH (0.1 mg kg-1) caused an increase in mean arterial
      blood pressure (MAP) from 9.8 +/- 1 to 11.8 +/- 0.8; a higher dose (1 mg kg-1)
      increased the blood pressure to 15.2 +/- 1 kPa (P less than 0.001). Total
      cerebral blood flow (CBFtot) increased to 137 +/- 10% (P less than 0.05) of
      control at the lower dose and to 214 +/- 16% (P less than 0.001), at the higher
      dose. A reduction in blood flow at both doses of TRH in several peripheral organs
      indicates that the pressor effect was mainly due to an effect on the peripheral
      vascular resistance. In prazosin-pretreated animals in which the MAP was
      normalized by ligation of the thoracic aorta, TRH elicited an increase in the
      CBFtot to 131 +/- 12% (P less than 0.05) of control. In the iris, TRH caused
      vasodilation in prazosin-pretreated animals. In experiments with combined alpha-
      and beta-adrenergic blockade, a non-adrenergic vasoconstricting effect of TRH was
      seen in some peripheral organs. The results indicate that TRH activates the
      sympathetic nervous system thus causing an increased vascular resistance and MAP;
      these effects are mediated mainly by an alpha 1-adrenergic mechanism. In the
      spleen, the gastric mucosa and the adrenal glands, the vasoconstriction caused by
      TRH was partly non-adrenergic. The vasodilation seen in the small intestine and
      the anterior uvea after TRH treatment and adrenoceptor blockade may be explained
      by effects on the parasympathetic nervous system. The vasodilating effect of TRH
      in the brain does not seem to involve alpha 1- or beta-adrenergic mechanisms.

PMID- 1359734
TI  - Effects of somatostatin on glucagon-stimulated glycogenolysis and gluconeogenesis
      in hepatocytes cultured in vitro.
AB  - The effects of somatostatin (SS-14) on glycogenolysis and gluconeogenesis in rat
      hepatocytes cultured in vitro in a serum-free medium were investigated.
      Somatostatin (122 nmol l-1) did not significantly change the basal glucose
      production with or without pyruvate (10 mmol l-1). Glucagon strongly (over 100%)
      increased the glucose production in hepatocytes incubated in a medium
      supplemented with 10 mmol l-1 pyruvate. This increase in glucose production is
      the result of increased rates of gluconeogenesis and glycogenolysis. Somatostatin
      partially inhibited the glucagon stimulated increase in glucose production.
      Glucagon also significantly increased the glucose production in a glucose-free
      medium without pyruvate, which resulted from an increase of glycogenolysis.
      Somatostatin did not inhibit the increase in glucose production in these
      conditions. After a 4 h 'fast', glycogen in hepatocytes fell to a very low level.
      Glucose production was minimal. After the addition of pyruvate, there was a
      increase in gluconeogenesis and glucose production. Glucagon stimulated the rate
      of gluconeogenesis. Somatostatin completely inhibited this glucagon-stimulated
      increase in gluconeogenesis.

PMID- 1359735
TI  - Effect of gamma-glutamyl transpeptidase inhibitors on the transport of glutamate
      into neuronal and glial primary cultures.
AB  - Inhibitors of gamma-glutamyl transpeptidase (mixture of serine and borate--13 mM,
      kainic acid--5 mM and 6-diazo-5-oxo-L-norleucine--2 mM) significantly suppressed
      glutamate uptake into cultured neurones and glial cells. The simultaneous
      application of any of these inhibitors with ouabain resulted in a further decline
      in glutamate uptake. It can be speculated that gamma-glutamyl transpeptidase
      significantly contributes to glutamate transport into nerve cells in the early
      period of brain development until the Na(+)-K(+)-gradient is fully constituted.

PMID- 1359737
TI  - Heparin binding properties of the carboxyl terminal domain of [A103,106,108]
      antistasin 93-119.
AB  - Antistasin is a 119 amino acid protein with anticoagulant, antimetastatic and
      heparin-binding properties derived from the salivary glands of the leech
      Haementaria officinalis (1). This protein contains a specific consensus sequence
      for heparin binding at its carboxyl terminal end and a region between residues 32
      and 48 putatively involved in glycosaminoglycan interactions. The cyclic peptide
      antistasin 37-48 (C-P-H-G-F-Q-R-S-R-Y-G-C) and the carboxyl terminal fragment
      [A103,106,108] antistasin 93-119 (P-N-G-L-K-R-D-K-L-G-A-E-Y-A-E-A-R-P-K-R-K-L-I-P
      R-L-S) were synthesized by solid-phase peptide chemistry and their interactions
      with 125I-labeled heparin were investigated. Heparin binding to [A103,106,108]
      antistasin 93-119 was specific and saturable as binding was blocked by addition
      of the unlabeled glycosaminoglycan. The rank order of potency of various
      glycosaminoglycans in blocking 125I-labeled heparin binding to [A103,106,108]
      antistasin 93-119 was dextran sulfate greater than heparin much greater than
      dermatan sulfate greater than or equal to chondroitin sulfate A and C indicating
      a specificity of the peptide for the glycosaminoglycan structure. Moreover,
      heparin binding increased linearly with increasing salt and was optimal at 0.15 M
      NaCl and physiological pH. In contrast, binding of heparin to the basic peptide
      antistasin 37-48 decreased linearly as the ionic strength of the medium was
      increased to physiological concentration (0.15 M) thus showing a greater
      specificity of heparin for [A103,106,108] antistasin 93-119. These studies
      indicate that residues 93-119 of antistasin mediate this inhibitor's interaction
      with heparin.

PMID- 1359738
TI  - The Biology and Prevention of Aerodigestive Tract Cancers. Proceedings from the
      Golden Jubilee Cancer Prevention Conference. Houston, Texas, February 21-23,
      1991.

PMID- 1359736
TI  - Anti-nef antibodies and other predictors of disease progression in HIV-1
      seropositive injecting drug users.
AB  - A cross-sectional and retrospective longitudinal study has been conducted in
      three Italian infectious disease centres to evaluate the role of anti-nef
      antibodies and other markers (HIV-1 p24 antigen, p24 Ag; Beta 2-microglobulin, B2
      M; and number of CD4+ lymphocytes) as predictors of disease progression in HIV
      seropositive injecting drug users (IDUs). The selected patients were: 1) HIV
      seropositive IDUs in different stages of HIV infection; 2) HIV-seropositive IDUs
      who had developed AIDS, from whom serial serum samples were available during the
      asymptomatic stage, and 3) HIV seropositive IDUs who remained asymptomatic
      through a follow-up period of the same duration as the patients who developed
      AIDS. Absence of anti-nef antibodies was associated with symptomatic HIV
      infection. A significant association between the absence of anti-nef antibodies,
      the presence of p24 Ag, high levels of B2-M, a number of CD4+ lymphocytes less
      than 500/ml at first visit and disease progression was found. Subjects who were
      persistently positive for antibody to nef were less likely to develop AIDS than
      those who were transiently or persistently negative. This difference was
      statistically significant (p = 0.03). The results of this study show that absence
      or disappearance of anti-nef antibodies may be used as predictor of disease
      evolution in HIV seropositive IDUs. This study also confirms the usefulness of
      other markers, such as p24 Ag, B2-M and number of CD4+ lymphocytes previously
      shown to be predictive of rapid disease progression for predicting the course of
      HIV seropositive IDUs.

PMID- 1359739
TI  - Exercise, calories, fat, and cancer. AICR 2d annual conference on nutrition and
      cancer. Pentagon City, Virginia, September 4-5, 1991.

PMID- 1359741
TI  - Proceedings of the 3rd meeting on Side Effects of Anti-Inflammatory Drugs and the
      13th European Workshop on Inflammation. Verona, Italy, May 8-11, 1991.

PMID- 1359740
TI  - The mechanism of action of drugs used to treat attention-deficit hyperactivity
      disorder: focus on catecholamine receptor pharmacology.

PMID- 1359742
TI  - Chronic intrajejunal TNBS application in TNBS-sensitized rats: a new model of
      chronic inflammatory bowel diseases.
AB  - An enteritis, based on a delayed-type hypersensitivity reaction, was induced in
      TNBS (2,4,4-trinitrobenzenesulfonic acid) sensitized rats by intrajejunal
      challenge with TNBS. This treatment induced a chronic inflammation of the distal
      small intestine, characterized by gross hyperaemia and oedema, as assessed by a
      macroscopic score. Histologically, the inflammatory response included cell
      infiltration by lymphocytes and histiocytes, a transmural granulomatous
      inflammation with multinucleated cells and activated mesenteric lymph nodes. Drug
      treatment with sulfasalazine or 5-aminosalicylic acid improved enteritis score.
      The applicability and relevance of this new model is discussed in relation to
      drug development and basic research of inflammatory bowel diseases.

PMID- 1359743
TI  - Therapeutic interventions in gastrointestinal disease based on an understanding
      of inflammatory mediators.
AB  - Whatever initiates inflammation, the final message mediating cellular invasion is
      chemical. This consideration allows rational development of anti-inflammatory
      treatments. Two main classes of chemotactic mediator are recognised. Water
      soluble peptides, e.g. cytokines derived from macrophages and other cells, play
      an important integrating part in the early recruitment of neutrophils and
      mononuclear cells, and in the amplification of immune responses. Lipid-soluble
      mediators, of which leukotriene B4 is the most highly chemotactic for
      neutrophils, are important in secondary amplification. In inflammatory bowel
      disease, we have shown evidence of increased synthesis of cytokines interleukin
      1, 6 and 8. These are associated with activation of circulating monocytes in
      active Crohn's disease, of lamina propria macrophages in relapse of both
      ulcerative colitis and Crohn's disease, and development of adhesion molecules on
      vascular endothelium. Our studies show that interleukin 6 is selectively
      increased in Crohn's disease, whilst preliminary findings suggest that enhanced
      synthesis of interleukin 8 is particularly characteristic of ulcerative colitis.
      Patterns of cytokine synthesis may, therefore, be of diagnostic value. They also
      offer the potential for therapeutic strategies since cytokine antagonists are
      becoming available. We have also demonstrated increased synthesis of leukotrienes
      in active inflammatory bowel disease. Since leukotriene B4 is quantitatively the
      main chemotactic signal in the mucosa in inflammatory bowel disease during
      relapse, we investigated the therapeutic effect of suppressing leukotriene B4
      synthesis by treating patients with fish oil (as Hi-EPA), giving 4.5 g daily of
      eicosapentaenoic acid. This competes for the 5-lipoxygenase enzymes, inhibiting
      leukotriene B4 and promoting synthesis of the less chemotactic product,
      LTB5.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359744
TI  - Cytokines and platelet-activating factor in human inflamed colonic mucosa.
AB  - Colonic biopsy specimens from patients with active ulcerative colitis and
      controls were incubated for four hours in the presence or absence of calcium
      ionophore or antihuman immunoglobulin E (IgE). Platelet-activating factor (PAF)
      was determined in the tissue by aggregation assay after extraction with 80%
      ethanol. PAF was not detected in normal mucosa, whereas A23187 and antihuman IgE
      stimulated its activity: mean +/- SE, 43.2 +/- 8.6 and 33.0 +/- 6.1 pg/10 mg wet
      weight, respectively. In active ulcerative colitis, A23187 and antihuman IgE
      induced significantly higher stimulation of PAF synthesis compared to their
      effects on normal mucosa. The enhanced stimulation of PAF induced by A23187 was
      dose-dependently inhibited by sulphasalazine, 5-aminosalicylic acid and
      prednisolone, but not by sulfapyridine. Colonic interleukin-1 content and release
      during 24 h of culture were significantly higher in patients with active
      ulcerative colitis and Crohn's disease compared to normal subjects. Prednisolone
      significantly and dose-dependently inhibited interleukin-1 release. These results
      suggest that colonic generation of PAF and interleukin-1 are elevated in patients
      with inflammatory bowel disease and, thus, may have a role in its pathogenesis.
      Pharmacological suppression of colonic PAF and interleukin-1 production may have
      beneficial therapeutic effects.

PMID- 1359745
TI  - 5-Lipoxygenase inhibitors for the treatment of inflammatory bowel disease.
AB  - The unique role of the enzyme 5-lipoxygenase (5-LO) in the production of
      leukotrienes (LTs) makes it a likely target for biochemical manipulation. The
      rationale for using 5-LO inhibitors for the treatment of inflammatory bowel
      disease (IBD) is based on the increased generation of LTs in the inflamed mucosa,
      LTB4 being the most potent chemotactic and chemokinetic metabolite of arachidonic
      acid. Furthermore, conventional drugs, such as corticosteroids, sulphasalazine,
      and 5-aminosalicylic acid, inhibit LT production and specific 5-LO inhibition
      accelerates healing in animal models of acute colitis. The compounds identified
      as 5-LO inhibitors can be divided into antioxidants, substrate-analogous, and a
      large miscellaneous group of inhibitors, where hydroxamic acids are potent and
      more selective inhibitors of 5-LO. The benzothiophene hydroxyurea, zileuton, is
      the first selective 5-LO inhibitor evaluated for the treatment of patients with
      IBD. An 800-mg oral dose of zileuton was shown to reduce LTB4, but not
      prostaglandin E2, concentrations by 75-85% in rectal dialysates from patients
      with active ulcerative colitis. The clinical efficacy of zileuton 800 mg b.i.d.
      has also been tested in a randomized, double-blind, placebo-controlled trial in
      similar patients. Zileuton significantly improved the symptom scores and the
      histology score, but not the sigmoidoscopy score, compared to pretreatment
      conditions and with response to placebo, the beneficial effects being most
      pronounced in patients not receiving concomitant sulphasalazine treatment. The
      mean inhibition of LTB4 in the target tissue of inflammation was 70%. The proof
      that any putative 5-LO inhibitor is blocking LT production is an important stage
      in assessing any such drug. The main disadvantage of existing new LT inhibitors
      relates to the high potency of LTs, and unless a higher level of inhibition can
      be achieved, endogenous LTs may still be present in sufficient amounts to produce
      their effects.

PMID- 1359746
TI  - Schistosomiasis and the social patterning of infection.
AB  - Social, cultural, behavioural and economic factors interact with local
      environmental and ecological factors to produce extraordinary variation in the
      epidemiology of schistosomiasis, including with respect to prevalence and
      intensity of infection and the potential for control. This article reviews the
      literature on schistosomiasis infection, primarily derived from African studies,
      to identify its major social themes. Research has demonstrated a strong link
      between economic development strategies, where irrigation has been introduced to
      boost agricultural production, and the increased transmission of infection. Water
      contact studies have provided the fullest and most detailed descriptions of
      social risk factors, and have isolated age, sex, religion and occupation as
      primary risk factors. However, fuller explorations of the social and cultural
      context of infection have yet to be undertaken. The social context of water
      related behaviour and patterns of water use within communities and households,
      the intersection of social and economic activities, and the significance that
      people give to these activities, remains poorly explored, and although research
      papers concerned with community-based interventions refer to poor community
      understanding of the cause, prevention and treatment of the disease, this domain
      has also received little scholarly attention. Finally, economic studies have
      focused primarily on working capacity, and extrapolated these findings to
      generalize about the impact that this might have on productivity, but have yet to
      address either household or community costs of schistosomiasis infection.

PMID- 1359747
TI  - Activity, mechanism of action and pharmacokinetics of 2-tert-butylbenzothiazole
      and CGP 6140 (amocarzine) antifilarial drugs.
AB  - A variety of recently developed drugs, designed to be used in antifilarial
      chemotherapy, contain a thiocarbonylamide group as a common structural element.
      One group of these compounds is based on a 2-tert-butylbenzothiazole ring in
      which the carbonylamide linkage is present as an isothiocyanate, dithiocarbamic
      acid ester or thiourea derivative. The single representative of another series is
      an N-methylpiperazine adduct of amoscanate (CGP 6140 or amocarzine). CGP 6140 is
      currently undergoing clinical trials in patients suffering from onchocercosis.
      All of the drugs with antifilarial activity affect the motility of filarial worms
      in vitro. The primary site of action of most of these compounds is the
      mitochondrion. The drugs result in the swelling of this organelle and also the
      inhibition of respiration and other associated metabolic functions. The
      dithiocarbamic acid esters (e.g., CGP 20376) are devoid of intrinsic antifilarial
      activity. Activity of these compounds requires conversion to the corresponding
      isothiocyanates. This occurs spontaneously in aqueous solution at physiological
      pH. The thiourea compounds were found to inhibit acetylcholinesterase activity by
      competing with its substrate. There is also evidence that the latter drugs are
      metabolized by a host-derived enzyme to their isothiocyanate analogs. CGP 6140
      affects both mitochondrial function and acetylcholinesterase activity. The
      biochemical effects of the antifilarial compounds were not found to be
      significantly different between mammalian and parasite test systems. Biochemical
      and pharmacokinetic studies suggest that the selective toxicity of the new series
      of drugs towards filarial parasites is most likely preferential drug uptake by
      the pathogen. The lack of a unique target for these compounds in the parasite may
      explain the side-effects seen upon their administration to humans.

PMID- 1359748
TI  - The influence of the size of the initial inoculum on the efficacy of
      isometamidium (samorin) on a stock of Trypanosoma congolense.
AB  - The effect of the number of trypanosomes in the initial inoculum on the minimum
      curative dose, was determined for an experimental infection of Trypanosoma
      congolense in mice treated with isometamidium. Mice were infected by the
      intravenous route and were then treated three hours later by intraperitoneal
      injection. The minimum curative dose was shown to be dependent on the size of the
      initial inoculum, with a difference of a factor of 7.5 as the initial inoculum
      was increased from 10(3) to 10(6) trypanosomes per mouse. It is concluded that
      this may be a significant variable for in vivo drug sensitivity test, and may
      also have implications for treatment of infections in the field.

PMID- 1359749
TI  - Influence of D(+)-glucosamine on infection rates and parasite loads in tsetse
      flies (Glossina spp.) infected with Trypanosoma brucei.
AB  - Teneral Glossina morsitans centralis, G. m. morsitans and G. pallidipes were
      infected with three different clones of Trypanosoma brucei in blood containing
      D(+)-glucosamine, an inhibitor of tsetse midgut lectin. On average, 5 days of
      D(+)-glucosamine treatment tripled infection rates, without affecting the
      proportion of infections that matured. Total infection rates were equal in males
      and females, but twice as many infections matured in males. Counts of parasites
      in the guts and salivary glands of 277 flies revealed order of magnitude
      differences among flies, with females consistently having 2-3-times as many
      parasites as males. Parasite numbers varied in a sex-specific manner among tsetse
      clone combinations, but these differences were not correlated with similar large
      differences in infection rates. D(+)-glucosamine treatment had no significant
      effect on parasite loads.

PMID- 1359750
TI  - Development of multiple drug resistance of Trypanosoma congolense in Zebu cattle
      under high natural tsetse fly challenge in the pastoral zone of Samorogouan,
      Burkina Faso.
AB  - Preliminary data from an ongoing epidemiological survey in the pastoral zone of
      Samorogouan (Kenedougou) indicate the occurrence of multiple-drug-resistant
      Trypanosoma congolense. Despite frequent trypanocidal drug treatments with
      diminazene aceturate (Berenil, Hoechst) at 7 mg/kg body weight (bw) at intervals
      of 2 to 4 weeks, no significant drop in the prevalence of African animal
      trypanosomosis (AAT) was observed. To examine a suspected drug resistance, 20
      Zebu cattle, naturally infected with T. congolense and/or T. vivax, were
      transferred in December 1989 from Samorogouan into a fly-proof stable. Diminazene
      aceturate at 7 mg/kg bw cured infections of T. vivax, but was ineffective against
      T. congolense. Likewise, treatments with homidium bromide (Ethidium, FBC) at 1
      mg/kg bw and isometamidium chloride (Trypamidium, Rhone Merieux) at 1 mg/kg bw,
      respectively, proved to be ineffective. Corresponding chemotherapeutic trials in
      previously unexposed Zebu bulls and Sahelian goats infected with one primary T.
      congolense isolate from Samorogouan demonstrated a high level of resistance to
      diminazene aceturate (7 mg/kg bw in cattle and 17.5 mg/kg bw in goats),
      isometamidium chloride (1 and 2 mg/kg bw i.v. in goats) and quinapyramine
      sulphate (Trypacide'S', Rhone Merieux) at 5 mg/kg bw in goats. The appearance of
      a multiple-drug-resistant strain of T. congolense emphasizes the urgent need for
      new chemical substances as trypanocidal drugs and the increasing importance of
      efficient vector control.

PMID- 1359751
TI  - An in vitro model for screening antileishmanial drugs: the human leukaemia
      monocyte cell line, THP-1.
AB  - Standard anti-leishmanial drugs were tested for their ability to inhibit the
      growth of intracellular amastigotes of Leishmania aethiopica, L. donovani and L.
      infantum in the human leukemia monocyte THP-1 cell line. Sodium stibogluconate
      and meglumine antimoniate were active against L. donovani with ED50 values of 8.9
      micrograms SbV/ml and 2.9 micrograms SbV/ml, respectively. L. aethiopica was less
      sensitive to sodium stibogluconate with an ED50 value of 25.3 micrograms SbV/ml
      while pentamidine had an ED50 value of 0.6 microM. Both L. donovani (ED50, 9.3
      microM), and L. aethiopica (ED50, 6.4 microM), were sensitive to aminosidine
      sulphate. An L. infantum isolate, clinically resistant to meglumine antimoniate
      treatment, had an ED50 of 22.2 micrograms SbV/ml. The toxic level of drugs on
      host cells was determined by colorimetric Methyl Tetrazolium (MTT) assay prior to
      activity tests. The results obtained with the THP-1 in vitro drug screening model
      were similar to those obtained in the mouse peritoneal macrophage model.

PMID- 1359752
TI  - Comparative evaluation of the colony-stimulating factors induction potential of
      Plasmodium cynomolgi-infected monkey erythrocytes and soluble antigens.
AB  - Plasmodium cynomolgi total antigens soluble in culture medium (P.c.SA), and
      noninfective P. cynomolgi-infected monkey erythrocytes (P.c.IE) were compared for
      their potential to induce colony-stimulating factors (CSFs). When injected
      intravenously in monkeys, both preparations induced an increase in the serum CSFs
      levels; P.c.IE appeared to be 1.6-fold more potent than the P.c.SA. In vitro
      P.c.IE induced 1.8-fold more CSF by monkey blood monocyte-derived macrophages
      than P.c. However, both in vivo and in vitro, the peak CSFs levels induced by
      P.c.SA were attained apparently 8 h earlier. CSF generated by P.c.SA and P.c.IE
      induced the formation of macrophage, granulocyte and granulocyte-macrophage
      colonies, in vitro; P.c.IE-generated CSF induced the formation of significantly
      (P < 0.01) higher numbers of granulocyte-macrophage colonies, indicating that the
      CSF induced by them stimulated different biological responses. The CSF induction
      appeared to be LPS-independent.

PMID- 1359753
TI  - Vector competence of Glossina pallidipes and G. morsitans centralis for
      Trypanosoma vivax, T. congolense and T. b. brucei.
AB  - Vector competence of Glossina pallidipes for pathogenic Trypanosoma species was
      compared to that of G. morsitans centralis. Cattle or goats were the hosts used
      to infect teneral tsetse, rabbits were used to maintain tsetse which were
      dissected on day 30. Mean infection rates of G. pallidipes and G. m. centralis by
      T. vivax isolated from a cow in Kenya were respectively 39.5 +/- 8.9% and 32.1 +/
      10.3% whilst for T. vivax isolated from a cow in Nigeria, they were 30.0 +/-
      7.5% and 19.8 +/- 4.3%. Differences were not significant. Differences in
      infection rates between the sexes of flies were also not significant.
      Transmission capability to goats by either tsetse species was good for the two T.
      vivax isolates. Mean infection rates by T. congolense isolated from a lion in
      Tanzania were significantly lower in G. pallidipes (8.5 +/- 1.8%) than in G. m.
      centralis (22.5 +/- 2.0%). Males of either tsetse were more susceptible than
      females. Transmission rates to goats and mice by both tsetse species was 100%. G.
      pallidipes (3.5%) was less susceptible than G. m. centralis (25.1%) to T.
      congolense isolated from a cow in Nigeria, but transmission rates to goats and
      mice by either tsetse was 100%. Also, G. pallidipes (2.7 +/- 0.4%) was
      significantly less susceptible than G. m. centralis (18.4 +/- 1.1%) to T. b.
      brucei isolated from a hartebeest in Tanzania. Males of either tsetse species
      were more susceptible than females. Transmission rates to goats and mice by
      either tsetse was 100%. G. pallidipes (0%) was not susceptible to T. b. brucei
      isolated from a pig in Nigeria whilst G. m. centralis showed infection rate of
      9.3%. When male G. pallidipes and G. m. centralis were fed every day for 27 days
      on a goat infected with this T. b. brucei from Nigeria, the infection rates were
      8.7% and 20.2%, respectively. Transmission rates to mice by either tsetse species
      was 100%. In conclusion, G. pallidipes has a vector competence equal to that of
      G. m. centralis for T. vivax, whilst G. pallidipes has lower vector competence
      than G. m. centralis for T. congolense and T. b. brucei.

PMID- 1359754
TI  - Sonographic organometry in Brazilian and Sudanese patients with hepatosplenic
      schistosomiasis mansoni and its relation to the risk of bleeding from oesophageal
      varices.
AB  - Fifty-nine patients with hepatosplenic schistosomiasis mansoni were investigated
      by sonography in Northeast Brazil and Central Sudan. The sizes of the organs
      usually involved in this disease were quantitatively assessed according to a
      standardized protocol, and measurements were adjusted to the body height of the
      individual. The results were compared with those of healthy controls matched by
      sex, age, geographical origin and socio-economic status. Considerable differences
      were found between patients and controls as well as between residents from the
      two areas. The liver of both patients and controls from the Sudan was
      significantly smaller than that of patients and controls from Brazil. Only in
      Brazil, but not in the Sudan, was the left liver lobe larger in patients than in
      the controls. The diameter of the portal and the splenic vein, the spleen size
      and the thickness of the gallbladder wall were significantly increased in
      patients from both areas. The increase of the portal and splenic vein diameter
      was significantly correlated with the degree of hepatic periportal fibrosis and
      the frequency of bleeding from endoscopically proven oesophageal varices in the
      patients, irrespective of their geographic origin. In contrast, such correlations
      were not found for the degree of splenomegaly nor for the degree of gallbladder
      wall thickening. It is concluded that standardized sonographic organometry
      permits the assessment of morbidity in hepatosplenic schistosomiasis mansoni
      under different endemic conditions. Especially the measurement of the portal vein
      diameter may allow estimation of the risk of gastrointestinal haemorrhage in
      these patients.

PMID- 1359756
TI  - Recombinant kinetoplast DNA (kDNA) probe for identifying Leishmania tropica.
AB  - The paper reports on the construction of a kDNA library with DNA isolated from
      the WHO reference strain of Leishmania tropica IC-305 and subsequent
      identification and propagation of recombinant plasmids containing L. tropica kDNA
      sequences. It also shows that the cloned kDNA sequences can be used as genetic
      markers in restriction endonuclease, Southern blot transfer, and dot blot
      hybridisation analysis, to identify L. tropica parasites. When the pL 305-I kDNA
      probe was used in hybridisation experiments with DNAs from various Leishmania
      reference strains, species and isolates from different host species and from
      different geographical locations, hybridisation was detected only with L.
      tropica, thereby suggesting that the insert in recombinant plasmid 305-I was
      species-specific. The probe is sensitive to the level of 10(3) parasites in dot
      blot hybridisation. Additionally, orthogonal field alternation gel
      electrophoresis (OFAGE) and transverse alternating field electrophoresis (TAFE)
      were used to characterise Leishmania reference strains and Leishmania species.
      The molecular karyotypes resolved by these techniques showed significant
      differences in the profiles of chromosomal sized-DNA molecules among species of
      Leishmania. The DNA karyotypes of the two reference strains of L. tropica (IC-305
      and NLB-067), while similar, were nevertheless distinct.

PMID- 1359755
TI  - In vitro killing of taeniid oncospheres, mediated by human sera from hydatid
      endemic areas.

PMID- 1359758
TI  - The role of temperature and nutritional status in flight initiation by Triatoma
      infestans.
AB  - Flight initiation in Triatoma infestans is associated with low nutritional status
      and increases with rising temperature; it appears to be largely independent of
      bug age and sex. A predictive model for the probability of flight initiation was
      constructed based on weight:length ratios of the bugs and maximum ambient
      temperature, both of which can be ascertained in the field. The model accurately
      predicted the proportion of bugs initiating flight in > 85% of the groups used in
      our study. The predictive equation was found to give significant fits with two
      independent data sets. From our results it might be expected that flight would be
      rare during colder (< 20 degrees C) months but that 5-10% of the normal
      population of an infested house would fly on any given night during the hotter
      months when temperatures approach 30 degrees C. If bug nutritional status falls
      significantly, this proportion could be expected to rise to 30%.

PMID- 1359757
TI  - Glycolipid and protein profiles of normal and Trypanosoma cruzi infected heart
      muscle cells.
AB  - Using Triton X-114, glycolipids and proteins were extracted from heart muscle
      cells (HMC) infected with Trypanosoma cruzi clone Dm28c and from uninfected HMC,
      and analysed by SDS-PAGE and high-performance thin-layer chromatography (HPTLC).
      Two major differences were observed: (a) two proteins with a molecular mass of 92
      kDa and 69 kDa were present in the uninfected cells but absent from the infected
      cells and (b) a 70-90 kDa protein band was detected only in parasitized cells.
      These differences would seem to constitute alterations taking place during the
      process of cell recognition and/or parasite interiorization. No differences were
      observed in the respective glycolipid compositions, of control and infected cells
      analysed by HPTLC. A glycolipid with the same mobility as the neutral glycolipid
      isolated from epimastigotes of T. cruzi was detected in the uninfected cells.
      This finding may lend support to the previously described hypothesis that
      molecular mimicry is implicated in the cardioneuropathology of Chagas' disease.

PMID- 1359759
TI  - Epidemiology of bovine brucellosis in the coastal savanna zone of Ghana.
AB  - 323 sera from cattle raised in four locations in a coastal savanna area of Ghana
      were screened for brucellosis using the Rose Bengal plate test. The overall
      prevalence rate was 9.3%. No significant difference was seen between the
      infection rates in females (11.3%) and in males (4.3%). Generally, regardless of
      the sex of the animal, older animals (> or = 2 years) had significantly higher
      infection rates (11.6%) than younger animals (3.5%). In the females, the older
      animals had a relatively higher infection rate (13.5%) compared to nil (0) for
      the younger ones. However, in the males the converse was true, with younger
      animals having a relatively higher infection rate (6%) compared to the matured
      males (2.4%). 31% of the 42 herds examined tested positive for brucella
      antibodies in the Rose Bengal plate test. The need to monitor bovine brucellosis
      and educate the population at risk on dangers of infection is emphasised.

PMID- 1359761
TI  - Plasmodicidal effect of desferrioxamine B in human vivax or falciparum malaria
      from Thailand.
AB  - Desferrioxamine B (DFO, Desferal), an iron chelator, was earlier shown to be
      active against Plasmodium falciparum in vitro and in vivo. The present open pilot
      study served to assess its clinical tolerability and efficacy in human malaria
      under hospital conditions. Continuous intravenous DFO was administered to 28 Thai
      males at a dose of 100 mg/kg over 24 h for 3 consecutive days. No other
      antimalarial therapy was administered unless recrudescence had occurred. The
      first 14 patients had symptomatic Plasmodium vivax (P.v.) malaria, while the
      other 14 patients were suffering from uncomplicated Plasmodium falciparum malaria
      (P.f.). Both groups were treated in Bangkok, where malaria transmission does not
      take place, and followed up, on the ward, for 3 weeks (P.v. group) or 4 weeks
      (P.f. group) after the start of therapy. In both groups DFO reduced the
      parasitaemia to zero within 106 and 57 h respectively. The fever clearance time
      was 55 and 60 h, respectively. The overall tolerability of DFO was good but 4
      P.v. and 5 P.f. patients had transient visual blurring. Recrudescences were
      observed on average 15, respectively 10 days after the start of therapy. Only 2
      P.v. patients and none of the P.f. patients remained free of recrudescences
      during the observation period. There was no apparent gametocytocidal effect of
      DFO on P.f.

PMID- 1359760
TI  - Diagnosis of New World leishmaniasis: specific detection of species of the
      Leishmania braziliensis complex by amplification of kinetoplast DNA.
AB  - We have sequenced single kinetoplast DNA minicircles from three species and part
      of a minicircle from the fourth major species within the Leishmania braziliensis
      complex. Alignment of these sequences with each other and with those of other
      kinetoplastids allowed the selection of a pair of oligonucleotides suitable as
      primers in a polymerase chain reaction which is highly specific for the
      Leishmania braziliensis complex. The reaction is capable of detecting less than
      one femtogramme of kinetoplast DNA. It has been tested with crude specimens from
      South American leishmaniasis patients, potential wild animal reservoirs and
      sandfly vectors. The tests indicate that these primers are suitable for diagnosis
      of leishmaniasis and potentially useful in epidemiological surveys.

PMID- 1359762
TI  - Structural differences between the chromatin of procyclic Trypanosoma brucei
      brucei and of higher eukaryotes as probed by immobilized trypsin.
AB  - Soluble chromatin of Trypanosoma brucei brucei procyclic culture forms was
      submitted to digestion with free or immobilized trypsin. Digestion with trypsin
      in salt solutions of low and high ionic strengths generated characteristic sets
      of limit histone peptides. After incubation of chromatin with immobilized trypsin
      in a solution of low ionic strength, histones were not degraded, whereas a
      selective proteolysis occurred at 50 mM NaCl. Histones a and d, which correspond
      to H3 and H4 of higher eukaryotes, were rapidly attacked. Histones b and c, the
      counterparts of H2A and H2B, were more resistant. The results indicated that
      probably the basic N-terminal tails of the proteins a and d are located on the
      surface of the core particle. The location of d on the surface differs from the
      internal one proposed for histone H4. The salt-induced increase of susceptibility
      of histones to proteolysis reflects structural changes of T.b. brucei chromatin,
      which may result in partial chromatin compaction.

PMID- 1359763
TI  - Axenic in vitro cultivation of Trypanosoma simiae bloodstream trypomastigotes.

PMID- 1359764
TI  - Quantitative reconstitution of isolated influenza haemagglutinin into liposomes
      by the detergent method and the immunogenicity of haemagglutinin liposomes.
AB  - The reconstitution of influenza virus haemagglutinin into liposomes from
      lipid/protein/detergent mixtures by detergent removal provides vesicles that are
      similar in structure to viral particles. The dissociation properties of
      haemagglutinin aggregates and the molar ratio of lipid to protein in the starting
      mixture are the key factors for the individual and total yield of protein
      incorporation into liposomes. Structural properties of the detergent used as well
      as special reconstitution conditions are of minor importance for the formation of
      haemagglutinin liposomes. As determined by radial immunodiffusion-, haemolysis-
      and fusion experiments, specific properties of haemagglutinin were maintained to
      a large extent on liposomal incorporation, but its immunogenicity is increased,
      if the antigen is incorporated into the lipid bilayer of liposomes.

PMID- 1359765
TI  - Antigenic and molecular analysis of influenza A(H3N2) virus strains isolated in
      1985 in open and closed communities of northern Germany.
AB  - Antigenic and molecular analyses of influenza A(H3N2) virus strains isolated in
      1985 during outbreaks in open and closed communities of North Germany were
      carried out. The data obtained have shown that 11 strains isolated in a closed
      orphanage were antigenically similar to each other. The electrophoretic
      mobilities of either HA, NP, M1 and NS1 polypeptides or of double stranded RNA
      segments were indistinguishable. Analysis of viruses isolated at the same time
      from open communities has revealed that they contained at least three groups of
      strains differing in homology of 3-5 RNA segments. These data support the idea
      that an outbreak of influenza in a community is caused by single virus strain,
      from which their slightly different variants of the virus arise during
      circulation among sensitive persons.

PMID- 1359766
TI  - Virus-specific immune response in the lungs of mice infected with influenza
      virus.
AB  - The time course of primary humoral immune response in NFS/N mice infected with
      the adapted influenza virus A/Aichi 2/68(H3N2) was followed by determination of
      the different class immunoglobulins in lungs, lung washings, and in blood serum.
      The quantity of antibody-producing cells (APC) was estimated by local haemolysis
      in gel. The presence of antibodies in serum and lavage fluid was tested by the
      methods of radial haemolysis and radial immunodiffusion. It was shown that the
      local immune response had developed earlier than systemic antibodies occurred in
      the serum.

PMID- 1359767
TI  - Virus neutralizing antibodies at different stages of the HIV disease: increased
      levels after azidothymidine treatment.
AB  - Specific HIV-1 neutralizing activity was measured in single serum samples
      obtained from 52 individuals suffering from different stage of HIV disease, as
      well as in serum samples collected during a four years follow up of other 13 HIV
      1 seropositive persons, from whose seven developed AIDS. Three of these persons
      were treated with azidothymidine. In the former group of single serum specimens,
      the specific neutralizing antibody positivity rate was 81 per cent in symptomless
      persons, 92 per cent in patients with ARC and 43 per cent in patients with AIDS.
      From 13 HIV-1 infected individuals, prospectively investigated from 1986 to 1990,
      six remained asymptomatic and no significant fluctuation of specific virus
      neutralizing antibody levels was noted. During this time period, remaining seven
      patients developed AIDS. In the sera of AIDS patients, specific neutralizing
      activity was either not detected or its titres were rather low before the
      appearance of clinical disease. Three AIDS patients were administered
      azidothymidine. Specific neutralizing antibody titres increased significantly one
      month after the beginning of azidothymidine administration and persisted at
      relatively high levels over several months of follow up.

PMID- 1359768
TI  - On the antiviral activity of diffusomycin (oxazolomycin).
AB  - The effect of the beta-lactone antibiotic diffusomycin (oxazolomycin) was
      investigated against vaccinia (Lister), herpes simplex type 1 (Kupka), influenza
      A (WSN; H1N1), and Coxsackie A9 viruses. Diffusomycin reduced significantly the
      plaque formation of enveloped DNA and RNA viruses by more than 90% in the range
      of the maximally tolerated dose. As could be shown with vaccinia virus, the
      antiviral action was not caused by virucidal effect on virions or by interaction
      with virus adsorption and penetration. In one-step growth cycle assays
      diffusomycin prevented the replication of herpes simplex type 1, vaccinia and
      influenza A viruses in a dose-dependent manner. The replication of influenza A
      viruses was blocked immediately after addition of the compound during zero to six
      hr p.i. Partial reversibility of the antiviral action was established by washing
      off the antibiotic from chicken embryo cells (CEC) infected with influenza A
      virus. Finally, replication of Coxsackie A9 virus was not inhibited by
      diffusomycin. Electron-optical studies revealed a reduced synthesis of HSV-1
      nucleocapsids in dependence on the concentration of the compound.

PMID- 1359769
TI  - Molecular characterization of cloned variants of Coxiella burnetii isolated in
      China.
AB  - To study the molecular properties of Coxiella burnetii phase variants we cloned
      the phase variants of C. burnetii Qiyi (CBQY) strain by the red plaque technique.
      Three cloned strains, CBQYIC3 (phase I), CBQYIIC7 (phase II) and CBQYIIC5
      (semirough-phase) were analysed by SDS-PAGE, immunoblot assay, plasmid isolation
      and agarose gel electrophoresis of DNA restriction fragments. The results suggest
      that the unique phase-dependent substance is a lipopolysaccharide and that most
      protein components of phase I and phase II cells are shared. No significant
      differences of DNA restriction fragments were found between clonal isolates of
      phase I and phase II C. burnetii CBQY strains. A plasmid of approximately 56 Kb
      was isolated from both phase I and phase II variants indicating that phase
      variation probably could not be attributed to its presence or absence.

PMID- 1359770
TI  - Analysis of the coat proteins of the ordinary and Andean strains of potato virus
      S and antigenic comparisons of carlaviruses.
AB  - The coat proteins of both ordinary (PVSO) and Andean (PVSA) strains were shown to
      be similar in molecular weights, peptide maps, amino acid analysis and reaction
      to a range of carlavirus antiseras.

PMID- 1359771
TI  - Characterization, purification and serology of the Czechoslovak isolate of radish
      mosaic virus.
AB  - The radish mosaic virus 1 (RMV 1) isolate was characterized according to the
      reaction of differential test plants and then purified by the chloroform-butanol
      method. UV-analysis of sucrose density gradients at 254 nm revealed three
      components. The values of A260/280 ratio were 1.42 for the top, 1.49 for the
      middle and 1.67 for the bottom component, respectively. Electron microscopy of
      the purified virus revealed isometric particles about 30 nm in diameter. Two
      antisera were prepared with the titre 1:1024 and 1:2048, respectively. The RMV 1
      antigen formed a distinct precipitation line with the antiserum against the
      California neo-type strain of RMV.

PMID- 1359772
TI  - Some physicochemical properties of murine herpes virus.
AB  - The effect of incubation temperature variation and various pH values on the
      stability of murine herpesvirus isolate-76 (MHV-76) was investigated. The virus
      survival in rabbit embryo fibroblasts cells (REF) has been determined. At room
      temperature (23 degrees C) 50% of the virus became inactivated during 12 days and
      at 37 degrees C its half life was 9 days. MHV-76 was completely inactivated at 50
      degrees C in 1 hr or at 41 degrees C in 7 hrs. MHV-76 retains its maximal
      infectivity at the pH range between 6-9 regardless of the duration of treatment.
      The pH range 3, 4, 5 and 10, 11, 12 caused either complete or more or less
      expressed inactivation of the virus. A complete inactivation MHV-76 was also
      achieved after treatment with ethyl ether, chloroform and 2M urea.

PMID- 1359773
TI  - Skin virulence of attenuated pseudorabies virus (PRV) strains.
AB  - After intradermal inoculation of the attenuated pseudorabies virus (PRV) strains,
      Bartha, MK35 (gI+) and MK35-T-2 (gI-) to rabbits, they caused local inflammatory
      nodules with oedema reddiness and necrosis. The specifity of these reactions was
      confirmed by their inhibition with anti-PRV serum. The minimal dose that caused
      visible skin reaction was about 10(2) TCID50/ml for Bartha and MK35-T-2 (gI-)
      strains and over 10(4) TCID50/ml for the MK35 (gI+) strain. It is assumed that
      the established residual skin virulence can serve as an additional distinction
      marker for attenuated PRV strains.

PMID- 1359774
TI  - DNA regions and genes determining the virulence of herpes simplex virus.
AB  - The outcome of virus-host interaction after peripheral inoculation of herpes
      simplex virus (HSV) depends on virus replication at the portal of entry, the
      ability of the virus to invade nerve endings and capillary endothelium cells and,
      the rate of virus replication in neurons and nonneural cells of the nervous
      system. Functions involved are the activity of viral thymidine kinase, DNA
      polymerase, immediate early transactivator proteins, the transcription initiation
      protein, the envelope protein(s) governing virus penetration, syncytium formation
      and natural killing of infected cells as well as some other regulatory DNA
      sequences.

PMID- 1359775
TI  - A recombinant immunodot assay for determination of HIV-1 GP41 antibody titres.

PMID- 1359776
TI  - Basic structural features of a lipopolysaccharide from the Coxiella burnetii
      strain Nine Mile in the virulent phase I.

PMID- 1359778
TI  - Exercise treadmill testing.

PMID- 1359777
TI  - Salmeterol xinafoate: a review of its pharmacological properties and therapeutic
      potential in reversible obstructive airways disease.
AB  - Salmeterol xinafoate, like salbutamol (albuterol), is a saligenin derivative, and
      a selective beta 2-adrenoceptor agonist. It produces bronchodilation for at least
      12 hours following inhalation of a single 50 micrograms dose. Salmeterol is
      intended for regular twice-daily treatment of reversible airways obstruction and
      not for immediate symptomatic relief, and when used in this manner. 50 micrograms
      twice daily is more effective than salbutamol 200 micrograms or terbutaline 500
      micrograms administered 4 times daily, or individually titrated oral doses of
      theophylline in improving objective and subjective criteria of efficacy in
      patients with mild to moderate asthma. Salmeterol 100 micrograms inhaled twice
      daily may provide better control than the lower dose in patients with severe
      asthma. The long duration of effect of salmeterol makes it particularly suitable
      for treating patients with nocturnal asthma in whom it improves sleep quality.
      The place of salmeterol, like that of other beta 2-adrenoceptor agonists used
      regularly in the treatment of asthma, is being debated. Patients in need of
      regular beta 2-agonist therapy should also be regarded as candidates for inhaled
      corticosteroids to counteract underlying inflammation. Thus, salmeterol may be
      particularly useful in patients requiring regular treatment with beta 2-agonists
      for nocturnal asthma and results of trials in progress involving large numbers of
      patients are awaited with interest.

PMID- 1359780
TI  - A Symposium: Coronary Artery Disease: Mechanisms for Myocardial Protection.
      Aventura, Florida, December 6-7, 1991.

PMID- 1359779
TI  - T-cell receptor gene polymorphisms in familial cardiomyopathy: correlation with
      anti-beta-receptor autoantibodies.
AB  - Cardiac autoantibodies have been detected in a significant proportion of patients
      with dilated cardiomyopathy, but their relation to the pathogenesis of the
      disease remains unknown. This issue was examined in 41 members of an Ohio family
      with a heritable disorder of the cardiac conduction system and the myocardium. In
      41.5% of all members studied, serum anti-beta-receptor antibodies were identified
      by a combination of techniques: ligand binding inhibition assay, enzyme-linked
      immunoassay of a beta 1-receptor peptide, and adenylate cyclase inhibition. The
      prevalence of autoantibodies was significantly higher (p < 0.01) in the affected
      (64.7%) than in the unaffected (25.0%) members. A 10.0 kb restriction fragment
      length polymorphism of the C beta region of the T-cell receptor gene was also
      overrepresented in affected males (60% versus 30% unaffected males, p < 0.01). In
      males, the presence of anti-beta-receptor antibodies was linked to the 10.0 kb C
      beta polymorphism. In affected males, a BlgII C alpha 2.14 kb polymorphism was
      also more frequent (62% versus 32% in unaffected, p < 0.01) and was linked to the
      presence of anti-beta-receptor antibodies. The distribution of haplotypes defined
      by V beta 8, C alpha, and C beta probes was significantly different between
      affected and unaffected (p < 0.04) and between antibody-positive and antibody
      negative individuals. Since the major function of the T-cell receptor is the
      recognition of processed autoantigens, these results provide additional support
      for the role of autoimmunity in dilated cardiomyopathy.

PMID- 1359781
TI  - Instantaneous cardiac death in the posthospital period after acute myocardial
      infarction.
AB  - Sudden arrhythmic cardiac death is a major unresolved health problem, yet there
      is no agreement on the chronologic definition of sudden death. This retrospective
      study investigates the frequency distribution of the chronology of the terminal
      cardiac event in a large postinfarction population and identifies factors
      associated with instantaneous (< 1 minute) cardiac death. This study involved 229
      patients enrolled in the Multicenter Diltiazem Post-infarction Trial who died
      during 2-year follow-up and had quantitative information on the chronology of the
      terminal event. Thirty-two percent of the cardiac deaths occurred
      instantaneously. Patients who died instantaneously were more likely (p < 0.05) to
      be men, to have a baseline ejection fraction < 0.40, and to have frequent (> or =
      10/hour) and repetitive (> or = 3 in a row) ventricular ectopic complexes (VECs)
      on an ambulatory electrocardiogram than those who did not die instantaneously.
      Patients who died instantaneously received more digitalis and class IA
      antiarrhythmic agents and less beta blockers in the week before death than those
      dying noninstantaneously. Logistic regression analysis identified 3 independent
      factors that differentiated instantaneous from noninstantaneous death (relative
      risk; 95% confidence interval): frequent VECs (2.15; 1.11 to 4.17); digitalis
      (2.57; 1.31 to 5.06); and no beta blocker medication (2.90; 1.09 to 7.75).
      Instantaneous death (within 1 minute) was responsible for almost one third of the
      cardiac deaths that occurred in this postinfarction population. Frequent VECs,
      digitalis, and absence of beta-blocker therapy distinguished patients who died
      instantaneously from those who died noninstantaneously.

PMID- 1359782
TI  - Pulmonary infiltrates and skin pigmentation associated with sulfasalazine.
AB  - A patient with ulcerative colitis developed skin pigmentation and diffuse
      pulmonary shadowing without respiratory symptomatology, while taking
      sulfasalazine. The clinical picture and radiological abnormalities disappeared
      spontaneously on discontinuation of the drug. Histopathological studies from
      specimens taken by transbronchial biopsy showed bronchiolitis obliterans with
      fibrosing alveolitis. Sulfasalazine-induced lung disorder is an extremely rare
      entity which must be considered in all ulcerative colitis patients while on
      sulfasalazine therapy, despite the absence of pulmonary symptomatology.

PMID- 1359783
TI  - Familial IgA nephropathy: a study of HLA class II allogenotypes in a Chinese
      kindred.
AB  - We have studied the restriction fragment length polymorphism (RFLP) of the major
      histocompatibility complex (MHC) class II DQ, DR pattern of a Chinese family with
      IgA nephropathy (IgAN). The three affected and one apparently unaffected sibling
      shared the same DR and DQ pattern. The subjects were homozygous for DRw12, DQw7,
      DQ alpha 1b. The DQw7 allele was further confirmed by polymerase chain reaction
      (PCR) and allele-specific oligonucleotide (ASO) probing. This study confirms that
      IgAN can run in a family and is consistent with the possible immunopathogenetic
      effects of MHC class II antigens on IgAN.

PMID- 1359784
TI  - Renal artery stenosis modifies glomerular injury in antineutrophil cytoplasmic
      antibody-associated disease.
AB  - A 68-year-old man presented with renal failure, heart failure, gastrointestinal
      bleeding, and a pulmonary infiltrate. Serologic evaluation revealed a perinuclear
      antineutrophil cytoplasmic antibody (ANCA) at a titer of 1:1280, which on
      immunoblot and enzyme immunoassay showed antimyeloperoxidase specificity. Autopsy
      showed microscopic polyarteritis based on the presence of necrotizing alveolitis
      and crescentic glomerulonephritis. The extent and activity of the glomerular
      disease was modified by a right renal artery stenosis (RAS). Twenty percent of
      glomeruli on the right and 82% glomeruli on the left contained crescentic
      lesions. Furthermore, predominantly active lesions were associated with renal
      artery stenosis, while the contralateral kidney contained mostly organized
      crescents. This observation suggests that hemodynamic factors or its sequelae can
      influence the onset and severity of ANCA-associated disease.

PMID- 1359785
TI  - The many faces of scleroderma.
AB  - This review integrates the clinical aspects of systemic sclerosis (SSc;
      scleroderma) and scleroderma-like conditions with new knowledge of the control of
      blood vessel tone and the role of anoxia in the activation of connective tissues
      leading to fibrosis. Serologic tests, high resolution computed tomographic
      scanning, bronchoalveolar lavage, and physiologic assessment of pulmonary gas
      diffusion are compared as diagnostic tools and as means of quantitating internal
      organ involvement. Treatment of Raynaud's disease and phenomenon, management of
      scleroderma renal crisis, and new means for improving gastrointestinal function
      with octreotide, the somatostatin analogue, also are discussed. The relationship
      between idiopathic forms of SSc and eosinophilic fasciitis/eosinophilia-myalgia
      syndrome caused by L-tryptophan ingestion and the scleroderma-like disease
      associated with silicone breast implants also is discussed.

PMID- 1359786
TI  - Elevated sulfatide excretion in heterozygotes of metachromatic leukodystrophy:
      dependence on reduction of arylsulfatase A activity.
AB  - Sulfatide excretion in urine and arylsulfatase A (ASA) activity in leukocytes
      were determined in 10 homozygotes of metachromatic leukodystrophy (MLD), 7
      obligate and 5 facultative MLD heterozygotes, 6 low ASA subjects (not related to
      MLD homozygotes), and in 9 controls. As compared to controls (sulfatides: 0-2
      nmol/mg lipid; ASA: 101-287 nmol p-nitrocatechol/mg protein/hr), MLD homozygotes
      displayed highly increased sulfatide excretions (27-280 nmol) and low residual
      ASA activities (0-13 nmol). Of 12 MLD heterozygotes (ASA: 18-87 nmol) 10 showed
      increased sulfatides (3-24 nmol). All heterozygotes with ASA activity < 60 nmol
      (n = 8) had elevated sulfatide excretions (4-24 nmol). Thus, reduction of ASA
      activity below 40% of the mean value of controls seems to be the critical
      threshold for elevated sulfatide excretion in MLD heterozygotes. The low ASA
      subjects (ASA in the heterozygote range) excreted sulfatides in the control
      range, even those with ASA activities < 60 nmoles (n = 3; including a definite
      homozygote for ASA-pseudodeficiency; ASA:25 nmol). Statistical evaluation of
      sulfatide excretion and ASA activity in all subjects (n = 37) revealed a
      significant inverse relation (Spearman rank correlation; R = 0.8278, P < 0.001).
      The finding of elevated sulfatide excretion in certain MLD heterozygotes might
      point to increase of sulfatides also in the nervous system.

PMID- 1359787
TI  - Survival and disease progression in human immunodeficiency virus-infected women
      after an index delivery.
AB  - OBJECTIVE: Our objective was to provide information on survival and disease
      progression in human immunodeficiency virus antibody-positive pregnant women
      undergoing prospective evaluation. STUDY DESIGN: After an index delivery, 103
      human immunodeficiency virus antibody-positive pregnant women were identified and
      underwent follow-up for 3 years. The patients were assessed medically and/or
      gynecologically when hospitalized for a human immunodeficiency virus-related
      illness or at each follow-up visit. The life-table method was used to estimate
      the cumulative probabilities of survival and remaining free of acquired
      immunodeficiency syndrome. Cox's proportional-hazards analyses were used to
      identify prognostic factors for survival and progression to acquired
      immunodeficiency syndrome. RESULTS: The majority of human immunodeficiency virus
      infected pregnant women were alive 3 years later. Lymphadenopathy syndrome or
      herpes genitalis was significantly associated with a subsequent diagnosis of
      acquired immunodeficiency syndrome. Of the 103 original patients, six had
      acquired immunodeficiency syndrome at the index delivery and acquired
      immunodeficiency syndrome developed in 24. Approximately 94% of evaluable
      patients with development of acquired immunodeficiency syndrome had CD4
      lymphocyte counts < 200/mm3. The most common opportunistic infection was
      Pneumocystis carinii pneumonia. Acquired immunodeficiency syndrome and postpartum
      zidovudine therapy were independent prognostic factors affecting survival.
      CONCLUSION: Survival was affected by Centers for Disease Control group status of
      human immunodeficiency virus infection at the index delivery.

PMID- 1359788
TI  - Anti-CD2 monoclonal antibodies prevent spontaneous and adoptive transfer of
      diabetes in the BB/Wor rat.
AB  - We studied the effects of anti-CD2 monoclonal antibodies (MAb) on spontaneous and
      induced autoimmune diabetes mellitus in diabetes-prone (DP) and diabetes
      resistant (DR) BB/Wor rats. In DP rats, all anti-CD2 MAb prevented spontaneous
      diabetes and the adoptive transfer of diabetes with Con-A--stimulated acute
      diabetic spleen cells; OX34 prevented Poly I:C induced accelerated onset of
      diabetes and the adoptive transfer of diabetes with Con-A--stimulated RT6.1+ T
      cell depleted DR splenocytes. In DP rats, all anti-CD2 MAb except OX53 depleted
      CD4+ T cells, without depleting natural killer cells or CD8+ T cells. OX34
      injected DR rats were profoundly depleted of CD4+ T cells without evidence of
      decreased CD8+ T cells, but were not protected against the induction of diabetes
      by RT6.1+ T-cell depletion and Poly I:C injections. We conclude that anti-CD2
      MAbs protect against BB/Wor autoimmune diabetes by depleting CD4+ T cells,
      preventing the activation of effector cells, or by blocking CD2/ligand
      interaction between effector and target cells.

PMID- 1359789
TI  - Multidrug resistance gene (P-glycoprotein) expression in the human fetus.
AB  - P-glycoprotein, a transmembrane protein associated with multidrug resistance in
      cancer cells, is also expressed in normal tissues. To get more insight into the
      physiologic role of mdr1/P-glycoprotein, we investigated its expression in human
      fetal tissues after 7 to 38 weeks of gestation by an immunohistochemical
      technique, using three different monoclonal antibodies, and by a sensitive RNAse
      protection assay. Expression of mdr1-mRNA could already be demonstrated in the
      embryonal phase of human development, after 7 weeks of gestation. Comparing the
      adult with the fetal tissue distribution, differences were found in specific
      organs, such as adrenal, intestine, respiratory epithelium, and brain
      capillaries. In the fetal zone cells of the fetal adrenal cortex no staining was
      observed by immunohistochemistry, whereas the definitive zone showed increasing
      expression throughout gestation. Prenatal intestine did not show staining of the
      epithelium, although definite mdr1-mRNA expression was observed in late
      specimens. Interestingly, respiratory epithelium of main bronchi and pharynx, not
      expressing P-gp in adults, did stain positive. Expression of P-gp in brain
      capillaries was not observed before the third trimester of pregnancy, whereas in
      kidney and liver, mdr1-mRNA expression and staining for P-glycoprotein were
      detected in early fetal life (11 to 14 weeks). These findings suggest a pivotal
      role of P-glycoprotein in physiology of various organs already in early phases of
      human development and may help to identify its physiologic substrates.

PMID- 1359790
TI  - Review of pharmacologic treatment of tinnitus.
AB  - Recent research on the pharmacologic treatment of tinnitus is reviewed,
      emphasizing studies in which controls have been used. Several double-blind cross
      over studies have found that lidocaine can reduce tinnitus in about 50 to 75
      percent of subjects. Unfortunately, it cannot be used clinically because it must
      be administered intravenously and its effects are very brief. Other drugs have
      been much less successful. A few controlled studies have found success rates
      between 33 and 56 percent using oxazepam, clonazepam, sodium amylobarbitone,
      flunarizine, and eperisone hydrochloride. None of these studies have been
      replicated, however. Closely controlled studies using specified etiologic
      subgroups with subjective and objective psychophysical measurements are needed.

PMID- 1359791
TI  - C-type natriuretic peptide inhibits growth factor-dependent DNA synthesis in
      smooth muscle cells.
AB  - We have examined the ability of C-type natriuretic peptide (CNP) to interact with
      guanylate cyclase-coupled natriuretic peptide receptors by measuring its ability
      to stimulate intracellular guanosine 3',5'-cyclic monophosphate (cGMP)
      accumulation in cultured bovine aortic endothelial (BAE) and bovine aortic smooth
      muscle (BASM) cells. Our experiments indicate that CNP is unable to stimulate the
      production of cGMP in BAE cells, whereas both atrial natriuretic peptide (ANP)
      and brain natriuretic peptide (BNP) markedly elevate cGMP levels in these cells
      (ANP = BNP >> CNP). In contrast, CNP is the most effective of the three peptides
      with respect to the stimulation of cGMP levels in BASM cells, fetal human
      vascular smooth muscle cells, and rat A10 cells (CNP >> ANP > BNP), with the
      maximal level of stimulation being approximately 5- to 10-fold over that observed
      for ANP. We have also shown that CNP is able to inhibit serum- and growth factor
      induced DNA synthesis in BASM cells. Low concentrations of CNP (20 x 10(-9) M)
      inhibit up to 80% of the [3H]-thymidine incorporation induced by basic fibroblast
      growth factor, platelet derived growth factor, epidermal growth factor (EGF), and
      heparin binding EGF-like growth factor. These data indicate that, although CNP
      has been detected only in the central nervous system and not in the circulation,
      it may possess multiple effects on vascular tissue.

PMID- 1359792
TI  - Ca(2+)-activated K+ channels in pregnant rat myometrium: modulation by a beta
      adrenergic agent.
AB  - The properties of Ca(2+)-activated K+ currents and channels were characterized in
      pregnant rat myometrium in whole cell and cell-attached patches and in lipid
      bilayers. Membrane depolarization of cultured myometrial cells from a holding
      potential of -50 to +70 mV in 10-mV steps under voltage-clamp conditions (whole
      cell mode) activated K+ outward currents (IK). At +70 mV, in the presence of 0.2
      mM external Ca2+, the amplitude and activation time constant of IK were 15.0 +/-
      2.1 microA/microF and 1.5 +/- 0.2 ms, respectively. Addition of 1 microM A23187
      to the external solution increased the current from a control value of 16.0 +/-
      2.0 to 67.9 +/- 9.1 microA/microF. Charybdotoxin, a blocker of Ca(2+)-activated K
      (KCa) channels, and a low concentration of tetraethylammonium chloride (TEA; 1
      mM) decreased the amplitude of IK by 47 and 62%, respectively. In cell-attached
      patches from these cells, 1 microM A23187 increased the open time probability of
      a 143 +/- 6.0 pS K+ channel. Incorporation of plasma membrane vesicles from
      pregnant myometrium into lipid bilayers resulted in one predominant type of K+
      channel. The unitary conductance of the K+ channel was 326 +/- 9.0 pS in
      symmetrical 450 mM KCl. The channel activation was both voltage and Ca2+
      dependent. TEA inhibited the channel activity with a dissociation constant (Kd)
      of 378 +/- 10 microM at -60 mV or 1,477 +/- 80 microM at +60 mV. The whole cell
      currents were found to be stimulated by isoproterenol, a beta-adrenergic
      agent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359793
TI  - Alpha 1-adrenergic stimulation of Na-H exchange in cardiac myocytes.
AB  - The activation of Na-H exchange in adult rat heart myocytes was characterized in
      response to a phorbol ester (phorbol 12-myristate 13-acetate) and an alpha 1
      adrenergic agonist [6-fluoronorepinephrine (6F-NE)]. Transport activation was
      assessed by determining the initial rate with which intracellular pH (pHi) was
      returned from an acid pulse and by following changes in steady-state pHi; pHi was
      determined by a pH-sensitive fluorescent dye. Both agonists shifted the
      intracellular pH dependence of Na-H exchange by 0.10-0.15 pH units in the
      alkaline direction. This shift was prevented by the presence of sphingosine and 1
      (5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), inhibitors of protein kinase
      C. The agonists also alkalinized pHi at steady state. The alkalinization by 6F-NE
      was blocked by prazosin and H-7. This indicates that the adrenergic stimulation
      of cardiac Na-H exchange is mediated by an alpha 1-adrenergic mechanism and very
      likely involves the activation of protein kinase C.

PMID- 1359794
TI  - Regulation of protein synthesis by modulation of intracellular calcium in rat
      liver.
AB  - The rate of protein synthesis can be modulated in intact cells by varying the
      concentration and subcellular distribution of intracellular calcium. Because the
      biochemical reactions required for the pathway of protein synthesis occur in the
      cytosol of the cell, it might be expected that protein synthesis would be
      controlled by free cytosolic calcium rather than the sequestered cation. However,
      a recent report proposed that maintenance of optimal rates of protein synthesis
      depends on the amount of calcium sequestered in the endoplasmic reticulum rather
      than free cytosolic calcium (C.O. Brostrom and M. A. Brostrom, Annu. Rev.
      Physiol. 52: 577-590, 1990). In the present study, rat livers were perfused with
      buffer containing various compounds previously shown to alter intracellular
      calcium concentration and distribution in isolated cells. It was found that
      conditions designed to cause a rise in free cytosolic calcium had no effect on
      protein synthesis. In contrast, conditions designed to cause depletion of
      sequestered calcium resulted in an inhibition of protein synthesis characterized
      by a reduction in peptide-chain initiation relative to elongation. The inhibition
      of protein synthesis was further localized to a decrease in the activity of
      eukaryotic initiation factor (eIF) 2B as measured in extracts from perfused
      livers. The inhibition of eIF-2B activity was associated with a 2.4-fold increase
      in the proportion of the alpha-subunit of eIF-2 in the phosphorylated form. In
      summary, the results of the present study support a model whereby mobilization of
      calcium sequestered in the endoplasmic reticulum results in an inhibition of
      protein synthesis in rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359795
TI  - Hypothalamic neuropeptide Y inhibits gastric acid output in rat: role of the
      autonomic nervous system.
AB  - Injection of neuropeptide Y (NPY) into the hypothalamic paraventricular nucleus
      (PVN) inhibits gastric acid secretion in anesthetized rats. The role of the
      autonomic nervous system in mediation of this response was investigated.
      Unilateral microinjection of 200 pmol NPY into the PVN of anesthetized rats
      inhibited spontaneous and pentagastrin-stimulated gastric acid output. Inhibition
      was abolished by subdiaphragmatic vagotomy, atropine, and bethanechol but was
      restored by electrical stimulation of the distal cut end of the vagus in
      cervically vagotomized rats. Although sympathectomy, phenoxybenzamine, and
      yohimbine abolished the inhibition, it was not affected by prazosin treatment.
      Gastric blood flow was not altered by injection of NPY. These results suggest
      that the antisecretory effect of NPY in the PVN was sympathetically mediated via
      suppression of gastric vagal cholinergic tone through activation of alpha 2
      adrenoceptors.

PMID- 1359796
TI  - Pharmacokinetics and organ specific metabolism of glycine-extended and amidated
      gastrin in sheep.
AB  - Glycine (Gly)-extended gastrin has been described as the inactive precursor form
      of the biologically active amidated gastrin. The ratio of Gly-extended to
      amidated gastrin is higher in the circulation than in tissue, suggesting either
      differential secretion and/or metabolism. Although the distribution of the
      precursor form is similar in tissue and circulation to its amidated product, the
      significance of measurable levels of precursor peptide in the circulation is
      unknown. In this study, we have examined the pharmacokinetic properties and organ
      specific metabolism of both the Gly-extended and the amidated forms of gastrin-17
      (G-17-Gly and G-17-amide) in the conscious sheep. The metabolic clearance rate,
      half disappearance time, and production rates were similar for both G-17-Gly and
      G-17-amide. G-17-Gly was extracted across the head, kidney, and lung but not
      across the gut and liver. Similarly, G-17-amide was extracted across the head,
      gut, lung, and kidney but not across the liver. G-17-Gly had no biological
      activity as evidenced by its failure to stimulate somatostatin secretion nor was
      there any measurable conversion to amidated gastrin in the circulation. We
      conclude that the presence of G-17-Gly in the circulation is not the result of a
      slower clearance and that circulating G-17-Gly is not a precursor for circulating
      gastrin-amide. The results of this study provide important baseline data for
      understanding the dynamics of the precursor product relationship between G-Gly
      and G-amide.

PMID- 1359797
TI  - Novel sites for expression of an Escherichia coli heat-stable enterotoxin
      receptor in the developing rat.
AB  - Escherichia coli heat-stable enterotoxin (STa) mediates diarrheal disease by
      binding to and activating an intestinal transmembrane receptor, guanylate cyclase
      C (GC-C). To test the hypotheses that there was 1) increased perinatal expression
      of GC-C in rat intestine and 2) GC-C expression and STa binding in
      extraintestinal tissues of immature rat, we prepared whole cell membranes and
      total RNA from jejunum, ileum, colon, liver, kidney, heart, lung, brain, testis,
      and placenta of rats ranging in age from 12 days gestation to adult. Northern
      analysis demonstrated the presence of a unique 3.8-kb mRNA transcript at all ages
      in the jejunum, ileum, colon, and, to a lesser degree, in the testis. GC-C was
      also detected by Northern analysis in liver (from gestational age 18 days through
      14 days postnatal) and in placenta. Steady-state mRNA encoding GC-C was not
      detected by Northern analysis in the other organs examined. GC-C-specific mRNA
      expression was greatest in the perinatal period in the jejunum, ileum, and liver.
      Specific binding of 125I-labeled STa was found in each of the tissue membranes in
      which GC-C mRNA was present; binding was not present in those tissues that had no
      detectable GC-C mRNA. The existence of GC-C in extraintestinal organs in the rat,
      and the development changes in GC-C expression support our hypothesis that GC-C,
      apart from its role as an STa receptor in mediating diarrheal disease, also
      serves as a receptor for an endogenous ligand.

PMID- 1359798
TI  - Reflex cardiovascular response to exercise is modulated by circulating
      vasopressin.
AB  - Peripheral vasopressin (AVP) can act centrally to sensitize the arterial
      baroreflex and/or peripherally to attenuate regional blood flow by a direct
      vascular effect. Because plasma concentrations of AVP increase during exercise,
      this study examined the possibility that AVP is capable of modulating the reflex
      cardiovascular response to static muscle contraction. Thus, in anesthetized cats,
      the pressor [mean arterial pressure (MAP)], myocardial contractile (dP/dt), and
      heart rate responses to 30-45 s of electrically induced static contraction of the
      hindlimb muscles were compared before and after intravenous injection of the V1
      receptor antagonist d[CH2)5Tyr(Me)]-AVP (V1-x, n = 7), V1-x plus the V2 receptor
      antagonist [d(CH2)5,D-Phe2,Ile4,Arg8,Ala9]vasopressin (V2-x, n = 5), or the
      ganglionic blocker hexamethonium chloride (n = 5). In three additional cats, the
      contraction-induced cardiovascular response was monitored before and after
      injection of V1-x + V2-x and after hexamethonium. Subsequent to treatment with V1
      x, the MAP and dP/dt responses to contraction were augmented by 18 +/- 5 and 22
      +/- 10%, respectively (P < 0.05). After injection of V1-x + V2-x, the MAP and
      dP/dt responses were augmented to a similar extent (32 +/- 6 and 40 +/- 17%,
      respectively; P < 0.05). However, there was no difference in the magnitude of
      augmentation of these responses between the two conditions. The heart rate
      response was not altered by either treatment. Ganglionic blockade eliminated the
      cardiovascular responses to contraction. Last, when the pressor and contractile
      responses to contraction were initially augmented by administration of V1-x + V2
      x, subsequent ganglionic blockade abolished the entire cardiovascular
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359799
TI  - Clinical and research implications of the diagnosis of dysphoric or mixed mania
      or hypomania.
AB  - OBJECTIVE: The authors reviewed available evidence regarding the status of
      dysphoric or mixed mania as a distinct clinical state and formulated operational
      criteria for its diagnosis. METHOD: Studies of dysphoric mania or hypomania in
      patients with bipolar disorder were analyzed with regard to clinical
      characteristics, prevalence, demographic features, course of illness, outcome,
      family history, associated conditions, biological tests, and response to
      biological treatment. RESULTS: Although some studies suggest that dysphoric and
      nondysphoric mania are similar conditions, others suggest that, compared with
      nondysphoric mania, dysphoric mania may be more severe; more likely to occur in
      women; more likely to be associated with suicidality, a younger age at onset, a
      longer duration of illness, higher rates of personal and familial depression,
      concomitant alcohol or sedative-hypnotic abuse, neuropsychiatric abnormalities,
      and poorer outcome; more frequently associated with cortisol nonsuppression; and
      less likely to respond adequately to lithium but perhaps more likely to respond
      to ECT or anticonvulsants. CONCLUSIONS: Substantial evidence suggests that
      dysphoric mania may be a distinct affective state. Contrary evidence, however,
      suggests that dysphoric mania may be a form of typical mania, a stage-related or
      severe form of mania, or a transitional state between mania and depression.
      Because the evidence may be inconsistent because of varying definitions of
      dysphoric mania among studies, the authors propose preliminary operational
      diagnostic criteria for the future study of dysphoric mania.

PMID- 1359800
TI  - Implications of the revised surveillance definition: AIDS among New York City
      drug users.
AB  - The Centers for Disease Control (CDC) has proposed revising the AIDS surveillance
      definition to include any HIV-seropositive person with a CD4 cell count of less
      than 200 cells per microliter. Based on a study of persons receiving treatment
      for HIV infection, this new definition would lead to an estimated 50% increase in
      the number of persons recognized as living with AIDS. Among 440 HIV-seropositive
      research subjects recruited from drug treatment programs and through street
      outreach in New York City, 59 met this definition, yet only 25% of those had been
      reported to the New York City AIDS registry. The new definition, if combined with
      HIV and T-cell testing at drug treatment and street outreach programs, could thus
      yield very large increases in the number of injecting drug users meeting the new
      surveillance definition of AIDS.

PMID- 1359801
TI  - The progression of untreated HIV-1 infection prior to AIDS.
AB  - Using a case-control study of untreated men, we investigated the physical,
      mental, and economic effects of human immunodeficiency virus (HIV-1) infection
      prior to the diagnosis of acquired immunodeficiency syndrome (AIDS). Beginning 2
      to 2.5 years prior to AIDS, case subjects reported more of 12 HIV-1 related
      symptoms and during the year prior to AIDS, at least 30.6 extra days of these
      symptoms than did control subjects. Within the 6 months preceding AIDS, case
      subjects' unemployment rose to 9% (P < or = .05) and depression to 34.2% (P < or
      = .001). At 6 to 12 months and within 6 months before AIDS, 17.1% and 31.5%,
      respectively, were anemic, while 37.7% and 64.7% had CD4+ counts less than 200 x
      10(6)/L. Diagnosing AIDS at CD4+ counts less than 200 x 10(6)/L could
      significantly reduce pre-AIDS morbidity. Other implications of these findings are
      discussed.

PMID- 1359802
TI  - Immunity to Hantavirus challenge in Meriones unguiculatus induced by vaccinia
      vectored viral proteins.
AB  - Vaccinia virus recombinants were constructed that incorporated genomic sequences
      coding for the nucleoprotein (N) and glycoproteins (G1 and G2) of the hantavirus
      R22 strain isolated from a rat in China, and designated as RNV and RMV9,
      respectively. The proteins expressed by RNV and RMV9 were identified by
      radioimmunoprecipitation and indirect immunofluorescence assay using a panel of
      monoclonal antibodies and polyclonal immune sera, and were found to be
      antigenically indistinguishable from authentic R22 viral proteins. Both RNV and
      RMV9 elicited an anti-R22 antibody response in Mongolian gerbils (Meriones
      unguiculatus) with titers ranging from 6,400 to 12,800 by enzyme-linked
      immunosorbent assay, but only RMV9 produced neutralizing antibodies to R22 virus
      (titer 1:200) and Hantaan (HTN) virus (titer 1:20). The ability of these
      recombinants to protect Mongolian gerbils against challenge with R22 and HTN
      viruses was examined. The RMV9 recombinant induced a complete protective immune
      response against challenge with 10(4) plaque-forming units (PFU) of both R22 and
      HTN viruses, while RNV induced partial protection against a challenge with the
      homologous R22 virus and the heterologous HTN virus at a dose of 10(3) PFU. Our
      data show that the common antigenic sites responsible for eliciting a protective
      response are located mainly on hantavirus glycoproteins, and that the
      nucleoprotein may also confer partial cross-protection that presumably involves
      cell-mediated as well as humoral mechanisms.

PMID- 1359804
TI  - A hazard of heated humidifiers.

PMID- 1359803
TI  - A comparison of the pharmacodynamics of rocuronium and vecuronium during
      halothane anaesthesia.
AB  - Thirty healthy patients were randomised to receive either a single bolus dose of
      rocuronium 0.6 mg.kg-1 or vecuronium 0.1 mg.kg-1 during halothane anaesthesia.
      Onset time, duration 25, duration 75 and train-of-four 70 were measured. The
      onset of neuromuscular blockade following rocuronium was more rapid than
      vecuronium (p = 0.0001). All other pharmacodynamic parameters were similar.
      During the first minute following injection of the neuromuscular blocking agent,
      the heart rate increased by 36% in the rocuronium group but remained stable in
      those patients who received vecuronium (p = 0.0008). No adverse effects were
      noted in either group.

PMID- 1359805
TI  - The hypnotic actions of alpha 2-adrenoceptor agonists.

PMID- 1359806
TI  - A microtiter plate transglutaminase assay utilizing 5-(biotinamido)pentylamine as
      substrate.
AB  - Transglutaminases belong to an important family of enzymes involved in
      hemostasis, skin formation, and wound healing. We describe a technique for the
      measurement of transglutaminase activity using polystyrene microtiter plates
      coated with N,N'-dimethylcasein. The substrate 5-(biotinamido)pentylamine is
      covalently incorporated into N,N'-dimethylcasein by transglutaminase in a calcium
      dependent reaction. The biotinylated product is detected by streptavidin-alkaline
      phosphatase and quantitated by measuring the absorbance at 405 nm following the
      addition of p-nitrophenyl phosphate. The assay is sensitive, specific, and linear
      at plasma factor XIIIa concentrations between 0.08 and 1.25 micrograms/ml and at
      purified guinea pig liver transglutaminase concentrations between 0.05 and 0.8
      microgram/ml. The intra-assay coefficient of variation is less than 8%. The solid
      phase assay was used to quantitate the transglutaminase activity in Escherichia
      coli extracts expressing recombinant factor XIII A-chains and to analyze factor
      XIIIa inhibitors. This method will facilitate the analysis of structure-function
      relationships of the transglutaminases using recombinant DNA methods.
      Furthermore, screening of natural and synthetic factor XIIIa inhibitors will be
      expedited by this solid-phase microtiter plate assay.

PMID- 1359807
TI  - Detection of neutral endopeptidase-24.11/CD10 by flow cytometry and
      photomicroscopy using a new fluorescent inhibitor.
AB  - Neutral endopeptidase (NEP; E.C. 3.4.24.11) is a mammalian ectopeptidase
      identified as the common acute lymphoblastic leukemia antigen (CALLA or CD10). In
      order to investigate its cellular processing and its role in B lymphocyte
      differentiation, a fluorescent derivative of the mercapto NEP inhibitor
      thiorphan, N-[fluoresceinyl]-N'-[1-(6-(3-mercapto-2-benzyl-1-oxopropyl) amino-1
      hexyl]thiocarbamide (FTI), has been synthesized. The fluorescent characteristics
      of fluorescein were conserved in FTI after linkage with the thiol NEP inhibitor.
      FTI inhibited NEP with an IC50 value of 10 nM and a good selectivity compared to
      that of aminopeptidase N (greater than 100 microM) and angiotensin converting
      enzyme (32 microM). The FTI probe was shown to detect membrane-bound NEP using
      photomicroscopy on cultured cells or flow cytometry techniques. Using NEP
      expressing MDCK cells and episcopic fluorescence microscopy, a specific labeling
      was obtained with 100 nM FTI which was completely displaced by 10 microM
      HACBOGly, a specific and potent inhibitor of NEP. Therefore, FTI can be
      considered a suitable tool for following cellular NEP traffic. In flow cytometry,
      the fluorescent probe FTI, used at concentrations as low as 1 nM with Reh6 cells,
      could be very useful for detecting NEP/CALLA on lymphoid cells. In addition, the
      recognition of FTI is independent of tissues and species, a major advantage of
      inhibitors over monoclonal antibodies.

PMID- 1359808
TI  - Intramuscularly administered dexmedetomidine attenuates hemodynamic and stress
      hormone responses to gynecologic laparoscopy.
AB  - The hemodynamic and endocrine effects of three different doses of dexmedetomidine
      (0.6, 1.2, and 2.4 micrograms/kg), oxycodone (0.13 mg/kg), and saline solution,
      injected intramuscularly 45-60 min before induction of general anesthesia, were
      compared in a double-blind, randomized study involving 100 women undergoing
      gynecologic diagnostic laparoscopy. Anesthesia was induced with thiopental (4.5
      mg/kg) and maintained with 0.3% end-tidal isoflurane and 70% nitrous oxide in
      oxygen. Arterial blood pressure and heart rate increased after endotracheal
      intubation and during laparoscopy in all groups, but the maximal mean arterial
      pressure after tracheal intubation was lower in the dexmedetomidine 2.4
      micrograms/kg group (104 mm Hg [SD 19]) than in the saline solution group (130 mm
      Hg [SD 12]). Dexmedetomidine (2.4 and 1.2 micrograms/kg) attenuated the maximal
      heart rate after intubation (84 [SD 11] and 101 beats/min [SD 15], respectively)
      compared with saline solution (116 beats/min [SD 19]). On the other hand, 40% of
      the patients in the dexmedetomidine 2.4-micrograms/kg group received atropine in
      the postanesthesia care unit for bradycardia (heart rate < or = 40 beats/min).
      Preoperative anxiety and sedation before and after preanesthetic medication were
      evaluated by the patients with the aid of a profile of mood-state questionnaire;
      only dexmedetomidine 2.4 micrograms/kg produced significant anxiolysis and
      sedation. Plasma concentrations of norepinephrine, epinephrine, 3,4
      dihydroxyphenylglycol, cortisol, and beta-endorphin increased less in the
      dexmedetomidine 2.4-micrograms/kg group in response to tracheal intubation and
      surgery than in the saline solution group.

PMID- 1359809
TI  - Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing
      abdominal hysterectomy.
AB  - The usefulness of intravenous dexmedetomidine infusion for maintenance of
      anesthesia was studied in patients anesthetized with thiopental, fentanyl,
      nitrous oxide, and oxygen. Isoflurane was added as needed. The study was
      conducted in two parts, the first of which was an open dose-response study that
      comprised 14 women undergoing abdominal hysterectomy. After a suitable infusion
      regimen of dexmedetomidine was determined according to hemodynamic criteria, 20
      patients were included in a double-blind, randomized placebo-controlled trial (10
      receiving dexmedetomidine, 10 saline solution). Dexmedetomidine was administered
      as a two-step infusion to rapidly achieve a steady-state plasma concentration.
      The infusion was started with an initial dose given over 10 min before the
      induction of anesthesia; at induction the maintenance rate was begun and
      continued until closure of the abdominal fascia. The infusion regimens of
      dexmedetomidine tested in the dose-response study ranged from 120 ng.kg-1 x min
      1, followed by 6 ng.kg-1 x min-1, to 270 + 13.5 ng.kg-1 x min-1. In the second
      part of the study, an initial infusion of 170 ng.kg-1 x min-1 was chosen,
      followed by 10 ng.kg-1 x min-1 for maintenance. Anesthesia was induced with
      thiopental (4.0 mg/kg) and maintained with isoflurane in 70% nitrous oxide and
      oxygen. Isoflurane was administered according to predetermined hemodynamic
      criteria. Dexmedetomidine infusion did not completely abolish the need for
      isoflurane but diminished its requirement by > 90% (P = 0.02). The heart rate
      response to endotracheal intubation was significantly blunted.

PMID- 1359810
TI  - Tyraminelike action of succinylcholine in the isolated, blood-perfused canine
      atrium.
AB  - The mechanisms of succinylcholine-induced cardiac effects have not been fully
      elucidated. Accordingly, we studied the effects of succinylcholine on atrial rate
      and contractile force in the isolated canine atrium perfused with donor blood.
      The sinus node artery was perfused with heparinized blood from the common carotid
      artery of the donor dog at a constant pressure of 100 mm Hg. When succinylcholine
      in a dose range of 30-1000 micrograms was injected directly into the sinus node
      artery of the isolated atrium, increases in atrial rate and contractile force
      were observed in a dose-related manner. The atrial rate and contractile force
      were increased to 10.5% +/- 1.8% (mean +/- SEM) and 56.8% +/- 8.5% above the
      control values after the administration of 1000 micrograms of succinylcholine,
      respectively. After treatment with propranolol, the positive chronotropic and
      inotropic effects of succinylcholine and norepinephrine were significantly
      suppressed. Hexamethonium or tetrodotoxin pretreatment inhibited the cardiac
      effects of nicotine but did not modify the succinylcholine-induced cardiac
      effects. The succinylcholine-induced effects were significantly inhibited by
      treatment with imipramine, which also suppressed the tyramine-induced effects. We
      conclude that succinylcholine has cardioexcitatory properties mediated by release
      of catecholamine due to a tyraminelike action.

PMID- 1359811
TI  - Alpha-2A is the predominant alpha-2 adrenergic receptor subtype in human spinal
      cord.
AB  - alpha-2 Adrenergic receptors can be subdivided into four subtypes based on their
      pharmacologic properties. The subtype of alpha-2 adrenergic receptor present in
      human spinal cord has not been reported previously. The affinities of nine alpha
      2 subtype-selective drugs for the alpha-2 adrenergic receptor in human spinal
      cord homogenates were determined using [3H]rauwolscine and [3H]RX821002. These
      drug affinities (pKi values) were highly correlated with those obtained in a
      tissue or cell line containing only the alpha-2A adrenergic subtype (correlation
      coefficient of 0.99 and 0.98 for human platelet and HT29 cells, respectively). In
      contrast, the correlation of pKi values for the human spinal cord with tissues or
      cell lines containing other adrenergic receptor subtypes was poor. The
      correlation coefficients for alpha-2B (neonatal rat lung), alpha-2C (OK cell),
      and alpha-2D (bovine pineal gland) were 0.15, 0.68, and 0.81, respectively. These
      data suggest that the predominant alpha-2 adrenergic subtype present in human
      spinal cord is the alpha-2A subtype. Both [3H]rauwolscine and [3H]RX821002
      appeared to label a single class of binding sites. The alpha-2 adrenergic
      receptor density was significantly greater in the sacral region of the cord as
      compared to either the lumbar or thoracic regions.

PMID- 1359813
TI  - High levels of linkage disequilibria between serologically defined class I bovine
      lymphocyte antigens (BoLA-A) and class II DQB restriction fragment length
      polymorphism (RFLP) in Norwegian cows.
AB  - Serum defined BoLA-A antigens, together with BoLA-DQB RFLP patterns, were
      determined in 87 almost unrelated Norwegian cattle. Statistical analysis revealed
      strong linkage disequilibria between these loci at the population level. A total
      of 13 haplotypes were found to be present at frequencies significantly greater
      than those predicted on the basis of their component gene frequencies. Among
      these, the subgroups 1A and 1B of the DQ1 haplotype were found to be closely
      associated with the class I antigens A11 and w16, respectively. The association
      between A11 and DQ1A is of particular interest, as two independent studies, one
      employing class I serology, and the other RFLP analysis of the class II locus DQ,
      have previously indicated that A11 and DQ1A confer relative susceptibility to
      mastitis.

PMID- 1359812
TI  - Direct coronary and cerebral vascular responses to dexmedetomidine. Significance
      of endogenous nitric oxide synthesis.
AB  - Dexmedetomidine activates alpha 2-adrenergic receptors in the central nervous
      system and in the peripheral vasculature. In vivo dexmedetomidine has been found
      to cause alterations in coronary and cerebral blood flows and arterial pressure
      by stimulation of vascular smooth muscle alpha 2 receptors. The direct
      vasoconstrictor effects of alpha 2-adrenergic agonists may be opposed by release
      of endothelium-derived relaxing factor believed to be nitric oxide. A functional
      endothelium was demonstrated recently in canine coronary collateral vessels. The
      objective of the current study was to assess the direct effect of dexmedetomidine
      on isolated canine proximal and distal coronary arteries, coronary collateral
      vessels, and middle cerebral arteries. Responses were measured in tissue baths in
      the presence of indomethacin 10(-5) M and in the absence and presence of NG nitro
      l-arginine methyl ester (L-NAME), an inhibitor of vascular nitric oxide
      synthesis. Dexmedetomidine (3 x 10(-8) to 3 x 10(-3.9) M) caused constriction
      (3.9, 5.5, 72.8, and 2.3% for proximal and distal coronary arteries, middle
      cerebral arteries, and coronary collateral vessels, respectively, expressed as a
      percentage of KCl-induced contraction) in all vessels. This constriction was
      enhanced by the presence of L-NAME in all vessels except cerebral arteries. The
      selective alpha 2-adrenergic antagonist atipamezole (10(-4) M) abolished the
      response to low but not high concentrations of dexmedetomidine in middle cerebral
      arteries, proximal coronary arteries, and coronary collateral vessels.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1359814
TI  - Assignment of the HOX2 and HOX3 gene clusters to the bovine chromosome regions
      19q17-qter and 5q14-23.
AB  - The homeobox 2 (HOX2) and homeobox 3 (HOX3) clusters have been chromosomally
      assigned in cattle by in situ hybridization. The probes employed were a murine
      probe for the mapping of HOX2 to 19q17-qter and human probes for the mapping of
      HOX3 to 5q14-q23. These assignments confirm the chromosomal assignment of two
      syntenic groups, consisting of loci located on human chromosome 12 (bovine
      chromosome 5) and the long arm of human chromosome 17 (bovine chromosome 19).

PMID- 1359815
TI  - COGNOSAG workshop report.

PMID- 1359817
TI  - [34th National Congress of Anesthesia and Resuscitation. 18-20 September 1992].

PMID- 1359816
TI  - [Consequences and prevention methods of hemodynamic changes during laryngoscopy
      and intratracheal intubation].
AB  - In patients ranked ASA 1, laryngoscopy and intubation lead to an average increase
      in blood pressure of 40 to 50%, and a 20% increase in heart rate. These changes,
      which are greatest one minute after intubation, last for 5 to 10 min. They are
      due to sympathetic and adrenal stimulation, which may also result in some
      arrhythmias. About half the patient with coronary artery disease experience
      episodes of myocardial ischaemia during intubation when no specific prevention is
      undertaken. Among the different means available for this, narcotics seem to have
      a reliable and constant effect, but they may be responsible for postoperative
      respiratory depression. The protective effect of fentanyl starts at 2
      micrograms.kg-1, and is at a maximum at 8 micrograms.kg-1. Lidocaine is the drug
      used most. Recent studies have questioned its efficacy. In clinical practice, it
      is particularly effective in preventing the pressor response to tracheal
      intubation, whatever its route of administration (intravenous or intratracheal),
      but not the increase in heart rate. Beta blockers with bradycardic,
      antihypertensive, antiarrhythmic and antiischaemic properties, have been
      advocated. As opposed to lidocaine, these agents are more effective in preventing
      the changes in heart rate than the pressor response. Because of their depressor
      effect on the myocardium, their place still remains to be defined, especially in
      the cardiac risk patient. Short-acting beta blockers should be preferred.
      Nitroglycerin is specifically indicated in coronary artery disease. Other agents,
      such as clonidine or calcium blockers, seem to be less effective or less
      convenient in preventing the haemodynamic alterations. In clinical practice,
      prevention will first rely on a sufficient dose of narcotics. In some cases,
      nitroglycerin or beta blockers may be used so as to decrease the doses of
      narcotics, without altering their efficacy; however, the risk of hypotension
      should be constantly borne in mind. If preventing measures have not been taken,
      short-acting antihypertensive agents (beta blockers, calcium blockers) should be
      used in patients who develop major hypertension during laryngoscopy and
      intubation.

PMID- 1359818
TI  - Nedocromil sodium inhibits the airway response to hyperosmolar challenge in
      patients with asthma.
AB  - We studied 16 asthmatic subjects sensitive to changes in airway osmolarity to
      determine whether nedocromil sodium has any effect on airway narrowing caused by
      hypertonic saline challenges. Nedocromil sodium (10 mg) or its vehicle was
      inhaled 10 min before a challenge with ultrasonically nebulized 4.5% NaCl. FEV1
      was measured before challenge and 1 min after each challenge period of 0.5, 1, 2,
      4, 8, 8 and 8 min. The challenge was stopped when there was a 20% fall in FEV1
      from baseline or after the final challenge period. We measured airway
      sensitivity, that is, the provoking dose of 4.5% NaCl required to induce a 20%
      reduction in FEV1 (PD20FEV1) and calculated the fold difference in PD20FEV1 after
      the intervention. After inhaling nedocromil sodium there was a 3.95-fold
      improvement in PD20 (p < 0.001) when compared with the vehicle day. After
      pretreatment with nedocromil sodium two of the 16 subjects were completely
      protected against 4.5% NaCl challenge, and six developed a plateau in their
      response. We conclude that nedocromil sodium is effective in reducing airway
      narrowing in response to 4.5% NaCl challenge in asthmatic subjects, and it
      appears to be unique in its ability to produce a plateau in response to acute
      administration of a drug before a bronchial challenge.

PMID- 1359819
TI  - Increased number of alveolar macrophages expressing adhesion molecules of the
      leukocyte adhesion molecule family in smoking subjects. Association with cell
      binding ability and superoxide anion production.
AB  - This study was designed to investigate whether the expression and functional
      properties of leukocyte adhesion molecules (LeuCAM; CD11/CD18) are altered in
      human alveolar macrophages (AM) from smokers. Cells were obtained from 38 smokers
      (S) and 27 nonsmokers (NS) by bronchoalveolar lavage (BAL). Expression of LeuCAM
      on freshly isolated cells was studied using a sensitive peroxidase-antiperoxidase
      method with monoclonal antibodies (mAB) against CD11a, CD11b, CD11c, and CD18.
      The functional properties of the adhesion molecules were studied by measuring in
      vitro the binding of AM to the intracellular adhesion molecule-1 (ICAM-1) on
      human umbilical-vein endothelial cells (HUVEC). The influence of LeuCAM on the
      increased superoxide anion production (O2-) of smoker AM was quantified after
      blocking the CD18 molecule by a mAB. Compared with nonsmoker AM, significantly
      more AM from smokers expressed CD11b (p < 0.001), CD11c (p < 0.001), CD18 (p <
      0.001), and CD11a (p < 0.004), whereas there was no difference in the expression
      of other common epitopes of human macrophages such as CD68, CD71, CD45, HLA-DQ,
      and HLA-DR. The number of AM expressing CD11a, CD11c, and CD18 showed a
      correlation to the total number of AM obtained by BAL (p < 0.001). Adherence of
      AM to HUVEC was higher for smoker than for nonsmoker AM (p < 0.05). The increased
      binding of smoker AM to endothelial cells could be inhibited by treating the
      HUVEC with a mAB against ICAM-1. The mAB anti-CD18 reduced O2- release from
      smoker AM by 42 +/- 5% after 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359820
TI  - Asthma: the important questions. Part 2.

PMID- 1359821
TI  - Airway Circulation. Proceedings from the 7th Transatlantic Airway Conference.
      Lucerne, Switzerland, January 1992.

PMID- 1359822
TI  - [Current diagnostic-therapeutic trends in carcinoids of the papilla of Vater].
AB  - Diagnosis and treatment of carcinoid tumor of the ampulla of Vater: case report.
      The carcinoid tumour of the ampulla of Vater is extremely rare. The authors
      report one case. Therefore, they dwell upon the problem connected with
      classifications, symptomatology and diagnosis of these neoplasms which present
      difficulty to diagnose preoperatively. At last, they reaffirm the primary role of
      pancreaticoduodenectomy with lymphadenectomy and, if it is possible, the
      necessity to extirpate the liver metastases.

PMID- 1359824
TI  - Beyond Deficiency: New Views on the Function and Health Effects of Vitamins.
      Conference proceedings. Arlington, Virginia, February 9-12, 1992.

PMID- 1359823
TI  - [Pleural manifestations in periarteritis nodosa, Wegener's disease and systemic
      lupus erythematosus].

PMID- 1359826
TI  - [Cutaneous pathology induced by cold].

PMID- 1359825
TI  - Effects of orally administered beta-adrenergic blockers and calcium-channel
      blockers on the intraocular pressure of patients with treated hypertension.
AB  - Little attention has been paid to the influence of orally administered
      antihypertensive drugs on intraocular pressure (IOP). Therefore, we evaluated the
      effects of oral medications on the IOPs and visual fields of 70 patients with
      systemic hypertension who had no ocular symptoms and had not visited any eye
      hospital. In patients with systemic hypertension treated with medication, the IOP
      value (mean, 18.3 +/- 4.2 mmHg; age range, 63.3 +/- 11.6 years) was significantly
      higher than in a control group with a similar age range who were not receiving
      oral medication (mean, 13.7 +/- 2.0 mmHg; age range, 62.5 +/- 7.8 years). In the
      group in which hypertension was controlled by medication, the IOPs were lower
      when orally administered beta-adrenergic blockers were given than in those
      patients with uncontrolled hypertension. In the group to whom calcium-channel
      blockers were administered orally, the IOPs were not lower. Angiotensin
      converting enzyme inhibitors made the visual fields worse. This study suggests a
      modulating influence of orally administered drugs on the IOP and visual fields,
      which may be affected by whether or not the patient's blood pressure is
      controlled.

PMID- 1359827
TI  - [Section of spermatic vessels (Fowler-Stephens procedure). A possible treatment
      for high undescended testis].
AB  - Although orchidopexy for an undescended testis is generally a satisfactory
      operation, high undescended testis is often a problem. Management of such
      testicles remains controversial and since 1984 the authors have used spermatic
      vessels division (Fowler Stephens procedure) in 29 cases with satisfactory
      results. Although the Fowler-Stephens procedure carries a certain risk of
      testicular atrophy, the results are equivalent to those achieved by the two stage
      orchidopexy if careful attention is paid to details of the procedure and
      selection of cases.

PMID- 1359828
TI  - [Do calcium inhibitors have any role in secondary prevention of myocardial
      infarction?].
AB  - The value of using calcium blockers in post-infarction secondary prevention is
      controversial. The HELD meta-analysis (1989) involving 17,759 patients concluded
      that they made no contribution in this indication (9.8% mortality rate vs 9.3% in
      the control group). The findings of the DAVIT II study with verapamil demonstrate
      a significant reduction in the infarction recurrence rate (18% vs 21.6%) in the
      treatment group. In the patients without heart failure, there was some benefit in
      terms of reduced mortality (7.7% vs 11.8%). The true contribution of calcium
      channel inhibitors, relative to that of beta-blockers in post-infarction
      medication should be analyzed in function of the various infarction sub-groups
      (no Q-wave, thrombolytic, with or without left ventricular dysfunction), of the
      calcium channel inhibitor being investigated and of the administration regimen.

PMID- 1359829
TI  - Immortalization of fibroblasts from two patients with hereditary retinoblastoma.
AB  - Two RB fibroblastic strains from patients with hereditary retinoblastoma (RB),
      namely, RB80F/250R and RB110F, were transfected with plasmid DNAs encoding SV-40
      large T-antigen at passage 31 and 10, respectively, These transfected fibroblasts
      developed into two immortalized cell lines. RB80F/250R/ori- and RB110F/gpt.
      RB110F/gpt had a similar doubling time as the parental cells, whereas
      RB80F/250R/ori- grew more rapidly with a doubling time of 19 hours compared to
      the parental cells which had a doubling time of 50 hours. The RB80F/250R/ori-
      cell line was particularly interesting cytogenetically since no normal chromosome
      13 was present, although a marker chromosome 13 was found. In contrast, two
      apparently normal chromosome 13s were present in RB110F/gpt cells, but these
      cells had a marker chromosome which involved chromosome 14 (14 p+). Both the cell
      lines also had an abnormal chromosome 1 (1q-). RFLP analysis using the chromosome
      13 specific VNTR probe, pTH162, assigned to 13q14.1 showed that the DNA from the
      RB80F/250R/ori- cells contained only a 6.1kb allelic fragment whereas the DNAs
      from parental RB80F/250R and RB80F cultures demonstrated both the polymorphic
      8.0kb and 6.1kb allelic fragments. However, the RB gene per se was normal at the
      DNA level. Both cell lines expressed SV-40 large T-antigen together with elevated
      levels of p53 protein. In addition, levels of RB protein were the same in
      exponentially growing nontransformed parental cell strains and their immortalized
      cell lines. However, at confluency the levels of RB protein were greatly reduced
      in nontransformed cells but not in immortalized cell lines under similar
      conditions. In future studies using these immortalized cell lines, we shall make
      an attempt to discern the role of the RB gene and other tumor suppressor genes in
      the regulation of normal and malignant growth.

PMID- 1359830
TI  - Genetic lesion in the carcinogenesis of cervical cancer.
AB  - Allelic loss at specific chromosomal loci was demonstrated in carcinoma of the
      cervix (CaCx) obtained from Hong Kong Chinese by restriction fragment length
      polymorphism analysis. Altogether 12 patients with CaCx, 7 with cervical
      intraepithelial neoplasia (CIN) and 7 with normal cervical tissues were studied.
      Polymorphic DNA markers for chromosome 3 were used and the tumour and
      constitutional genotypes of the above patients were compared. Loss of
      heterozygosity (LOH) was found in 10 out of 12 informative cases with CaCx at RAF
      1 locus (3p25) and in 10 out of 11 cases at D3S3 (3p14). Further study on
      patients with cervical intraepithelial neoplasia showed LOH at both 3p25 and 3p14
      in four out of five cases. In normal cervical tissues, no LOH was demonstrated at
      both loci. Our data suggest that the deletion events occurring on the short arm
      of chromosome 3 at 3p25 and 3p14 are early events in the development of carcinoma
      of cervix. Since recessive genes have been reported to reside within or close to
      these 2 loci, important genes may have been lost or inactivated in the genesis of
      this tumour. Moreover, human papillomavirus (HPV) type 16, 18 or 33 was found in
      8/12 of the carcinomas and 4/7 of CIN using Polymerase Chain Reaction and/or
      Southern Blot hybridization, confirming the close association with human
      papillomavirus. Whether the observed genetic lesions in the short arm of
      chromosome 3 in cervical "premalignant" and malignant lesions and their
      consistent association with high risk HPV represent independent events in the
      development of carcinoma of cervix will be discussed.

PMID- 1359831
TI  - Characterization of beta-adrenergic receptors in DiFi and HT-29 cells.
AB  - The beta-adrenergic receptors present in two human colorectal adenocarcinoma cell
      lines were characterized by measuring specific binding of [125I]-cyanopindolol
      (CYP). Whole, cultured, DiFi (derived from a familial adenomatous polyposis [FAP]
      patient) and HT-29 cells were used in radioligand binding assays. Scatchard
      analysis of specific 125I-CYP binding gave KDS of 38.6 +/- 5.7 pM in DiFi cells
      and 54 +/- 9.1 pM in HT-29 cells. However, binding site density (Bmax) in the
      DiFi cells was greater than that in HT-29 cells. In DiFi cells, the kinetically
      determined KD was similar to that calculated from Scatchard analysis. Studies in
      DiFi cells of the displacement of specific 125I-CYP binding by nonselective
      (propranolol), beta 1-selective (metoprolol and atenolol), and beta 2-selective
      (ICI 118-551) antagonists revealed only a single class of beta 2-adrenergic
      receptors. This provides the first evidence that colorectal adenocarcinoma cell
      lines contain beta-adrenergic receptors and shows that only beta 2-adrenergic
      receptors are present in DiFi cells. Mechanisms possibly affecting beta
      adrenergic-receptor expression in such cells are discussed in relation to colon
      carcinogenesis.

PMID- 1359832
TI  - Toremifene resistance in a rat mammary tumour model.
AB  - The effect of Toremifene on cell growth in vitro was tested on the R3230AC rat
      mammary adenocarcinoma as model. Toremifene differed from Tamoxifen in that it
      did not induce resistance; some cross-resistance was observed in Tamoxifen
      tolerant tumour cell lines. Toremifene does not influence P-glycoprotein
      expression in this model and at the levels studied.

PMID- 1359834
TI  - Abstracts of the 4th International Conference of Anticancer Research. Crete,
      Greece. October 21-25, 1992.

PMID- 1359833
TI  - Abstracts of the 4th International Conference of Anticancer Research. Crete,
      Greece, October 21-25, 1992.

PMID- 1359835
TI  - [Testicular ectopy. Current concepts].
AB  - Testicular descent is a complex mechanism influenced by hormonal and anatomical
      factors. Whatever the age of the patient or the descent technique used for either
      one or both testes, there is a risk of degeneration and sterility counts.
      Anatomical studies and the results of sperm are important, hence the importance
      of establishing a precise anatomical and therapeutic classification.

PMID- 1359836
TI  - Anti-IgG immobilized controlled-pore glass. Thionyl chloride-activated
      succinamidopropyl-glass as a covalent immobilization matrix.
AB  - Rabbit anti-bovine IgG was covalently immobilized on thionyl chloride-activated
      succinamidopropyl controlled-pore glass (CPG) beads (3000 A pore diam; 120/200
      mesh). Thionyl chloride-activated beads remained stable for over 1 y retaining
      full capability of immobilizing protein upon recirculation of protein solution.
      The immobilized anti-bovine IgG is capable of binding IgG with a dissociation
      constant (Kd) of 9.45 x 10(-7) M and a capacity of 0.85 g/L of matrix. A column
      of immobilized anti-IgG is able to remove all detectable contaminating IgG from
      partially purified enzyme preparations of sulfhydryl oxidase and gamma
      glutamyltransferase as determined by ELISA and Western blot. The column matrix
      could be regenerated by washing with 0.1M acetic acid, pH 2.8.

PMID- 1359837
TI  - Glutamine synthetase and nitrogen cycling in colonies of the marine diazotrophic
      cyanobacteria Trichodesmium spp.
AB  - We examined freshly collected samples of the colonial planktonic cyanobacterium
      Trichodesmium thiebautii to determine the pathways of recently fixed N within and
      among trichomes. High concentrations of glutamate and glutamine were found in
      colonies. Glutamate and glutamine uptake rates and concentrations in cells were
      low in the early morning and increased in the late morning to reach maxima near
      midday; then uptake and concentration again fell to low values. This pattern
      followed that previously observed for T. thiebautii nitrogenase activity. Our
      results suggest that recently fixed nitrogen is incorporated into glutamine in
      the N2-fixing trichomes and may be passed as glutamate to non-N2-fixing
      trichomes. The high transport rates and concentrations of glutamate may explain
      the previously observed absence of appreciable uptake of NH4+, NO3-, or urea by
      Trichodesmium spp. Immunolocalization, Western blots (immunoblots), and enzymatic
      assays indicated that glutamine synthetase (GS) was present in all cells during
      both day and night. GS appeared to be primarily contained in cells of T.
      thiebautii rather than in associated bacteria or cyanobacteria. Double
      immunolabeling showed that cells with nitrogenase (Fe protein) contained levels
      of the GS protein that were twofold higher than those in cells with little or no
      nitrogenase. GS activity and the uptake of glutamine and glutamate dramatically
      decreased in the presence of the GS inhibitor methionine sulfoximine. Since no
      glutamate dehydrogenase activity was detected in this species, GS appears to be
      the primary enzyme responsible for NH3 incorporation.

PMID- 1359838
TI  - Organization and nucleotide sequence of the glutamine synthetase (glnA) gene from
      Lactobacillus delbrueckii subsp. bulgaricus.
AB  - A 3.3-kb BamHI fragment of Lactobacillus delbrueckii subsp. bulgaricus DNA was
      cloned and sequenced. It complements an Escherichia coli glnA deletion strain and
      hybridizes strongly to a DNA containing the Bacillus subtilis glnA gene. DNA
      sequence analysis of the L. delbrueckii subsp. bulgaricus DNA showed it to
      contain the glnA gene encoding class I glutamine synthetase, as judged by
      extensive homology with other prokaryotic glnA genes. The sequence suggests that
      the enzyme encoded in this gene is not controlled by adenylylation. Based on a
      comparison of glutamine synthetase sequences, L. delbrueckii subsp. bulgaricus is
      much closer to gram-positive eubacteria, especially Clostridium acetobutylicum,
      than to gram-negative eubacteria and archaebacteria. The fragment contains
      another open reading frame encoding a protein of unknown function consisting of
      306 amino acids (ORF306), which is also present upstream of glnA of Bacillus
      cereus. In B. cereus, a repressor gene, glnR, is found between the open reading
      frame and glnA. Two proteins encoded by the L. delbrueckii subsp. bulgaricus gene
      were identified by the maxicell method; the sizes of these proteins are
      consistent with those of the open reading frames of ORF306 and glnA. The lack of
      a glnR gene in the L. delbrueckii subsp. bulgaricus DNA in this position may
      indicate a gene rearrangement or a different mechanism of glnA gene expression.

PMID- 1359839
TI  - The topology of the glutamine and ATP binding sites of human asparagine
      synthetase.
AB  - Human asparagine synthetase was examined using a combination of chemical
      modifiers and specific monoclonal antibodies. The studies were designed to
      determine the topological relation between the nucleotide binding site and the
      glutamine binding site of the human asparagine synthetase. The purified
      recombinant enzyme was chemically modified at the glutamine binding site by 6
      diazo-5-oxo-L-norleucine (DON), and at the ATP binding site by 8-azidoadenosine
      5'-triphosphate (8-N3ATP). The effects of chemical modification with DON included
      a loss of glutamine-dependent reactions, but no effect on ATP binding as measured
      during ammonia-dependent asparagine synthesis. Similarly, modification with 8
      N3ATP resulted in a loss of ammonia-dependent asparagine synthesis, but no effect
      on the glutaminase activity. A series of monoclonal antibodies was also examined
      in relation to their epitopes and the sites modified by the two covalent chemical
      modifiers. It was found that several antibodies were prevented from binding by
      specific chemical modification, and that the antibodies could be classified into
      groups correlating to their relative binding domains. These results are discussed
      in terms of relative positions of the glutamine and ATP binding sites on
      asparagine synthetase.

PMID- 1359841
TI  - T-cell activation is potentiated by cytokines released by lesional psoriatic, but
      not normal, epidermis.
AB  - BACKGROUND AND DESIGN: T-cell activation appears to be critical for the
      maintenance of psoriatic lesions. In this study, we determined whether cytokines
      released by epidermal cells from psoriatic lesions are providing signals that
      result in propagation of intralesional T-cell activation. Supernatants were
      obtained from epidermal cell cultures derived from skin biopsy specimens of
      psoriatic patients and normal subjects. These supernatants were added to purified
      normal CD4+ T cells activated via T-cell receptor (immobilized anti-CD3 and
      fibronectin) or via other activating pathways (anti-CDw60 or UM4D4). RESULTS:
      Psoriatic supernatants (n = 9), but not normal supernatants (n = 7, P < .0006),
      potentiated T-cell stimulation with anti-CD3 and fibronectin to 172% +/- 41% over
      control stimulation levels. The degree of lesional psoriatic epidermal cell
      potentiation correlated with the clinical severity of the lesion (r = .82, P =
      .007). Psoriatic epidermal cytokine potentiation of T-cell activation was not
      limited to T-cell receptor mediated stimulation; potentiation of anti-CDw60
      stimulated CD4+ T cells was also observed. Neutralizing antisera to interleukin 1
      and interleukin 8, but not interleukin 6, were found to reduce only partly the
      observed potentiation of T-cell activation. To determine whether cyclosporine is
      down modulating T-cell-potentiating cytokine activity in psoriasis, we compared
      samples obtained during a double-blind clinical trial of intralesional
      cyclosporine. T-cell-potentiating activity from psoriatic lesional sites treated
      with cyclosporine was not significantly modulated relative to the activity
      derived from vehicle-treated or untreated sites. CONCLUSION: These data
      demonstrate that lesional psoriatic epidermal cells release a balance of
      cytokines that potentiate T-cell activation. Because normal epidermal cells do
      not potentiate T-cell activation in this system, these findings demonstrate a
      mechanism by which the epidermis may non-specifically potentiate and perpetuate T
      cell activation in psoriatic lesions.

PMID- 1359840
TI  - [Recent results of anticancer drugs acting on microtubules--navelbine, taxol and
      taxotere for the treatment of lung cancer].

PMID- 1359842
TI  - [Laparoscopic orchidopexy].
AB  - The authors have experimented in the pig the possibility of endoscopic treatment
      of cryptorchidism. Sixteen orchidopexy procedures were performed utilizing 12
      Large White pigs weighing 10 to 15 kg. The procedure is described herin,
      including some details of anesthetic induction. The animal is placed in the
      Trendelenburg position and three trocars are inserted, in a position which
      corresponds to that of the umbilicus in humans (through which a laparoscope is
      passed), in the hypogastrium and in the hypochondrium of the corresponding side.
      The spermatic vessels are dissected all the way up to their origin and the vas
      deferens up to a short distance from the bladder. Then an incision is made in the
      inguinal canal, from the epigastric vessels up to the conjoined tendon. Pressure
      is applied outside until the testis is introduced into the peritoneal cavity
      where it is released by sectioning the sustenaculum testis. The cord is then
      pulled and passed in front of the epigastric vessels and taken out through the
      deep orifice of the inguinal canal. Once it is free in the peritoneum and after
      the vessels and the vas have been dissected, it is brought to the bottom of the
      scrotum with the grasping forceps and the aid of the hand outside. Then it is
      fixed with a suture through the skin. Finally, the incision in the inguinal canal
      is sutured with atraumatic nylon 0 suture as in the McVay technique for inguinal
      hernia repair. The procedure has started to be employed in the clinical setting.

PMID- 1359843
TI  - Acute joint inflammation alters the adrenoceptor profile of synovial blood
      vessels in the knee joints of rabbits.
AB  - Experiments were carried out to examine the effect of acute inflammation, induced
      by intra-articular injection of 2% carrageenan, on the response of articular
      blood vessels in the knee joints of rabbits to adrenoceptor agonists. The
      responses to noradrenaline, phenylephrine, clonidine, UK-14304, and isoprenaline
      were examined 24 hours after carrageenan injection and compared with those of
      normal animals. Antagonists specific for alpha 1 and alpha 2 were used to
      identify the adrenoceptors through which the responses were mediated and to
      examine if carrageenan treatment altered the adrenoceptor profile of these blood
      vessels. The evidence suggests that in the carrageenan treated animals there is a
      reduction in the alpha 1 response with an associated increase in the alpha 2
      response. A decrease in the number or affinity of alpha 1 adrenoceptors is
      indicated by the shift to the right of the noradrenaline and phenylephrine
      dose/response curves, whereas an increase in alpha 2 affinity or number is
      suggested by the associated leftward shift in the alpha 2 adrenoceptor agonist
      curves. This change in receptor profile appears to arise as a direct result of
      carrageenan induced joint inflammation.

PMID- 1359844
TI  - Radical surgery for gallbladder carcinoma. Long-term results.
AB  - The authors' objective was to evaluate the effectiveness of radical surgery with
      lymph node dissection for gallbladder carcinoma. Long-term results were analyzed
      in 40 patients in a 5-year study. The authors divided the 40 cases into two
      groups: 20 without positive nodes and 20 with positive nodes. In the group
      without positive nodes, one patient who underwent R1 resection died of a
      recurrence at 1 year 7 months. Seventeen of the 19 patients treated with R0
      resection survived more than 5 years. The 5-year survival rate was 85% (17/20).
      In the group with positive nodes, 9 of the 13 patients treated with R0 resection
      survived more than 5 years, whereas the seven patients treated with R1 or R2
      resection died within 5 years. The 5-year survival rate was 45% (9/20). Patients
      treated by R0 resection showed a 5-year survival rate of 69% (9/13). Thus we
      documented the favorable long-term results of radical surgery. R0 resection is a
      prerequisite for long-term survival. The results justify radical surgery with
      lymph node dissection.

PMID- 1359845
TI  - The adherence of endothelial cells to Dacron induces the expression of the
      intercellular adhesion molecule (ICAM-1).
AB  - The intercellular adhesion molecule (ICAM-1) is a glycoprotein expressed by
      endothelial cells activated by cytokines. The lymphocyte-function-associated
      antigen (LFA-1) is an integrin expressed by activated white blood cells.
      Together, this receptor-ligand pair is responsible, in part, for the localization
      of neutrophils at sites of inflammation. Using an in vitro model, the authors
      studied the binding of antibodies against ICAM-1 by human saphenous vein
      endothelial cells (HSVEC) adherent to Dacron and control cultureware. After
      adherence to Dacron pretreated with fibronectin, 24% more HSVEC-bound antibody
      against ICAM-1 compared with HSVEC on controls. In contrast, 90% more HSVEC
      adherent to Dacron incubated with whole blood bound anti-ICAM-1 antibodies. These
      cells bound 17.7-fold greater amounts of antibody compared with HSVEC on
      controls. Pretreating Dacron with plasma resulted in no increase in antibody
      binding compared with control. Our studies suggest that the cellular components
      of blood in contact with Dacron create a microenvironment that activates HSVEC
      and enhances ICAM-1 expression. Induction of this adhesion molecule may play a
      pivotal role in the migration and localization of leukocytes at the site of the
      vascular prosthesis.

PMID- 1359846
TI  - Toxic effects of zidovudine in asymptomatic human immunodeficiency virus-infected
      individuals with CD4+ cell counts of 0.50 x 10(9)/L or less. Detailed and updated
      results from protocol 019 of the AIDS Clinical Trials Group.
AB  - BACKGROUND: Protocol 019 of the AIDS Clinical Trials Group is a multicenter,
      double-blind, placebo-controlled trial of zidovudine (3'-azido-3'-deoxythymidine;
      formerly AZT) in human immunodeficiency virus-infected asymptomatic individuals.
      The initial results in the stratum of subjects entering with CD4+ cell counts of
      0.50 x 10(9)/L or less have been reported, but without a detailed analysis of
      toxic effects. METHODS: This detailed and updated report analyzes the toxic
      effects that occurred in 1567 subjects (91% men; 89% white) in this stratum of
      protocol 019 who received placebo (494 subjects), a 500-mg daily dose of
      zidovudine (544 subjects), or a 1500-mg daily dose of zidovudine (529 subjects).
      Hematologic, hepatic, and renal effects and patient-reported symptoms and
      clinical signs were monitored. RESULTS: Severe anemia (hemoglobin level, < 80
      g/L) was associated with both the 500-mg zidovudine group and the 1500-mg group
      compared with placebo. The estimated 18-month risks of severe anemia were 0.4%,
      2.0%, and 9.7% for the placebo, 500-mg zidovudine, and 1500-mg zidovudine groups,
      respectively. Predictive baseline measures were lower hemoglobin level in the
      1500-mg group and the two zidovudine groups combined and lower platelet count in
      the 500-mg zidovudine group. The risk of a first severe anemia developing was
      greatest in months 3 through 8 of treatment. Of the 44 subjects with severe
      anemia in the zidovudine groups, 18 (41%) progressed from mild anemia (hemoglobin
      level, 95 to 109 g/L) to severe anemia on consecutive visits (usually 2 to 4
      weeks apart). Severe neutropenia (absolute neutrophil count, < 750 x 10(6)/L) did
      not occur significantly more often in the 500-mg zidovudine group but did in the
      1500-mg zidovudine group. Moderate neutropenia (absolute neutrophil count, < 1300
      x 10(6)/L) did develop significantly more often in the 500-mg zidovudine group
      (165 subjects) than in the placebo group (71 subjects). Mild (or worse)
      elevations of bilirubin levels were uncommon but occurred more often with
      zidovudine. Severe nausea (and/or vomiting) was rare (2.8% of subjects) but was
      associated with zidovudine. Milder patient-reported events were common, and a
      number were associated with zidovudine. CONCLUSION: Zidovudine at the 500-mg/d
      dosage appears to be tolerable in many patients with asymptomatic human
      immunodeficiency virus infection and CD4+ cell counts of 0.50 x 10(9)/L or less.
      Increased clinical surveillance for anemia may be warranted in certain patients.

PMID- 1359847
TI  - Some properties of glutamate dehydrogenase, glutamine synthetase and glutamate
      synthase from Corynebacterium callunae.
AB  - Characteristics of the three major ammonia assimilatory enzymes, glutamate
      dehydrogenase (GDH), glutamine synthetase (GS) and glutamate synthase (GO-GAT) in
      Corynebacterium callunae (NCIB 10338) were examined. The GDH of C. callunae
      specifically required NADPH and NADP+ as coenzymes in the amination and
      deamination reactions, respectively. This enzyme showed a marked specificity for
      alpha-ketoglutarate and glutamate as substrates. The optimum pH was 7.2 for NADPH
      GDH activity (amination) and 9.0 for NADP(+)-GDH activity (deamination). The
      results showed that NADPH-GDH and NADP(+)-GDH activities were controlled
      primarily by product inhibition and that the feedback effectors alanine and
      valine played a minor role in the control of NADPH-GDH activity. The transferase
      activity of GS was dependent on Mn+2 while the biosynthetic activity of the
      enzyme was dependent on Mg2+ as essential activators. The pH optima for
      transferase and biosynthetic activities were 8.0 and 7.0, respectively. In the
      transfer reaction, the Km values were 15.2 mM for glutamine, 1.46 mM for
      hydroxylamine, 3.5 x 10(-3) mM for ADP and 1.03 mM for arsenate. Feedback
      inhibition by alanine, glycine and serine was also found to play an important
      role in controlling GS activity. In addition, the enzyme activity was sensitive
      to ATP. The transferase activity of the enzyme was responsive to ionic strength
      as well as the specific monovalent cation present. GOGAT of C. callunae utilized
      either NADPH or NADH as coenzymes, although the latter was less effective. The
      enzyme specifically required alpha-ketoglutarate and glutamine as
      substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359848
TI  - The effect of various culture conditions on the levels of ammonia assimilatory
      enzymes of Corynebacterium callunae.
AB  - Corynebacterium callunae (NCIB 10338) grows faster on glutamate than ammonia when
      used as sole nitrogen sources. The levels of glutamine synthetase (GS; EC
      6.3.1.2) and glutamate synthase (GOGAT; EC 1.4.1.13) of C. callunae were found to
      be influenced by the nitrogen source. Accordingly, the levels of GS and GOGAT
      activities were decreased markedly under conditions of ammonia excess and
      increased under low nitrogen conditions. In contrast, glutamate dehydrogenase
      (GDH; EC 1.4.1.4) activities were not significantly affected by the type or the
      concentration of the nitrogen source supplied. The carbon source in the growth
      medium could also affect GDH, GS and GOGAT levels. Of the carbon sources tested
      in the presence of 2 mM or 10 mM ammonium chloride as the nitrogen source
      pyruvate, acetate, fumarate and malate caused a decrease in the levels of all
      three enzymes as compared with glucose. GDH, GS and GOGAT levels were slightly
      influenced by aeration. Also, the enzyme levels varied with the growth phase.
      Methionine sulfoximine, an analogue of glutamine, markedly inhibited both the
      growth of C. callunae cells and the transferase activity of GS. The apparent Km
      values of GDH for ammonia and glutamate were 17.2 mM and 69.1 mM, respectively.
      In the NADPH-dependent reaction of GOGAT, the apparent Km values were 0.1 mM for
      alpha-ketoglutarate and 0.22 mM for glutamine.

PMID- 1359849
TI  - CD30-positive, anaplastic large-cell lymphomas that express CD15 but lack CD45. A
      possible diagnostic pitfall.
AB  - We report the immunohistochemical and clinical features of two cases of
      morphologically typical anaplastic large-cell lymphoma. One patient had lymph
      node and focal visceral involvement, and the other patient had multiple-organ
      involvement by lymphoma. In both cases, the lymphoma cells were CD30 (Ber-H2) and
      CD15 (Leu-M1) positive and CD45 (common leukocyte antigen) negative--a phenotype
      that is commonly seen in Hodgkin's disease. This unusual phenotype in large-cell
      anaplastic lymphoma led to an initial misinterpretation in one of the cases.
      Large-cell anaplastic lymphomas are highly variable, both in immunophenotype and
      clinical presentation. Because of this variability, a broad immunophenotypic
      panel, in conjunction with morphological features, should be used to establish
      the correct diagnosis.

PMID- 1359850
TI  - Neurologic disorders of attention and arousal: assessment and treatment.
AB  - Disorders of attention are common after a variety of insults to the central
      nervous system. Clinically observable disorders of attention have complex
      relationships to the hypothesized underlying core deficits that were reviewed in
      a previous article. Thus, the process of evaluating such deficits is equally
      complex. Treatments may be directed along a continuum from cellular chemistry and
      physiology to environmental modification. At present, there is little consensus
      about appropriate evaluation or treatment for attentional disorders.

PMID- 1359851
TI  - Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the
      pancreas.
AB  - Chemoradiation prior to pancreaticoduodenectomy ensures that all patients who
      undergo resection complete multimodality therapy, avoids resection in patients
      with rapidly progressive disease, and allows radiation therapy to be delivered to
      well-oxygenated cells before surgical devascularization. Twenty-eight patients
      with cytologic or histologic proof of localized adenocarcinoma of the pancreatic
      head received preoperative chemoradiation (fluorouracil, 300 mg/m2 per day, and
      50.4 Gy) with the intent of proceeding to resection; all 28 completed this
      preoperative therapy. Hospital admission because of gastrointestinal toxic
      effects was required in nine patients, yet no patient experienced a delay in
      operation. Restaging was performed 4 to 5 weeks after completion of
      chemoradiation, and five patients were found to have metastatic disease; the 23
      patients without evidence of progressive disease underwent laparotomy. At
      laparotomy, three patients were found to have unsuspected metastatic disease,
      three patients had unresectable locally advanced disease, and 17 patients were
      able to undergo pancreaticoduodenectomy. One perioperative death resulted from
      myocardial infarction, and perioperative complications occurred in three
      patients. Histologic evidence of tumor cell injury was present in all resected
      specimens. Our results suggest that pancreaticoduodenectomy can be performed with
      a low incidence of complications after chemoradiation for localized
      adenocarcinoma of the pancreas.

PMID- 1359852
TI  - Somatostatin in the management of gastrointestinal fistulas.

PMID- 1359853
TI  - Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their
      mixture. Part II: Structure-activity relationships with inhibition of hepatic
      phosphoenolpyruvate carboxykinase, pyruvate carboxylase, and gamma-glutamyl
      transpeptidase activities.
AB  - Male Sprague-Dawley rats were treated with an LD20, LD50 and LD80 respectively,
      of tetra-, penta-, hexa-, hepta-CDD and a mixture of the four CDDs, all carrying
      chlorine substituents in the biologically crucial 2, 3, 7, and 8 positions.
      Specific activities of two key enzymes of gluconeogenesis, viz,
      phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC), as well
      as the activity of the preneoplastic marker enzyme gamma-glutamyl transpeptidase
      (gamma-GT), were determined in livers of CDD-treated and ad libitum-fed control
      animals. PEPCK activity showed evidence for dose-related inhibition on the second
      day after dosing; PC activity was slightly reduced, whereas gamma-GT activity was
      dose-dependently inhibited. By 8 days after dosing PEPCK activities were dose
      dependently decreased after administration of all four CDDs and their mixture. PC
      activities were significantly reduced, but no dose-response was evident. The
      activity of gamma-GT was dose-dependently inhibited, but only to a value of 25%
      below control activities. It is concluded that CDDs share a common mechanism of
      acute toxicity, viz, inhibition of glucocorticoid-dependent enzymes which results
      in a derailment of intermediary metabolism not compatible with survival of the
      animals.

PMID- 1359855
TI  - The in vivo depletion of CD4+ T cells prevents antigen-induced eosinophil
      infiltration into mouse skin.
AB  - In order to determine the role of CD4+ T cells and CD8+ T cells in causing
      antigen-induced eosinophil infiltration into the site of late-phase reaction
      (LPR), we examined the effect of the in vivo depletion of CD4+ T cells and CD8+ T
      cells on antigen-induced eosinophil infiltration into mouse skin. Eosinophil
      infiltration into the skin of ovalbumin (OA)-sensitized BALB/c mice was biphasic
      after subcutaneous OA challenge, reaching the first peak at 6 h and the second
      peak at 24 to 48 h. The in vivo depletion of CD4+ T cells by pretreatment with
      anti-L3T4 monoclonal antibody (mAb) significantly decreased the second peak (at
      24 h and 48 h), but not the first peak (at 6 h), of OA-induced eosinophil
      infiltration into the skin of OA-sensitized mice. However, the depletion of CD8+
      T cells by pretreatment with anti-Lyt-2 mAb had no significant effect on either
      the first or second peak of OA-induced cutaneous eosinophilia in the mouse. These
      results indicate that CD4+ T cells, but not CD8+ T cells, play an important role
      in causing antigen-induced eosinophil recruitment of cutaneous LPR.

PMID- 1359854
TI  - Cell proliferation induced in the kidneys and livers of rats and mice by short
      term exposure to the carcinogen p-dichlorobenzene.
AB  - Cell proliferation in the kidneys and livers of rats and mice exposed short-term
      to p-dichlorobenzene (p-DCB) was evaluated by immunohistochemical measurement of
      bromodeoxyuridine (BrdU) incorporation into nuclei of DNA-synthesizing cells. p
      DCB was given by gavage at two doses up to 600 mg/kg body weight for 4 days. The
      cumulative fraction of proliferating cells was increased in the proximal tubule
      epithelial cells of male rats at the high dose, but not at the low dose nor in
      females at either dose using gamma-glutamyl transferase reaction to identify
      tubular cells. Also, no increase in cell proliferation was found in mouse
      kidneys. The fractions of proliferating cells in the livers of rats and mice of
      both sexes were also increased. The increased cell proliferation in only male rat
      kidney and in the livers of mice of both sexes correlates with the reported
      carcinogenic effects of p-DCB in those tissues. However, the finding that p-DCB
      also induced cell proliferation in the livers of rats of both sexes, which were
      not a site of p-DCB-induced tumors in bioassays, and in female mice at the low
      dose, which was not affected by an increase in tumors, reveals a lack of
      concordance and indicates that acute induction of cell proliferation is not
      sufficient to lead to carcinogenesis.

PMID- 1359856
TI  - Biphasic response of clonidine in isolated rat aortae.
AB  - Clonidine as a partial agonist of alpha adrenoceptor in Wistar rat aorta has been
      documented. It was however observed that the effect of clonidine on the isolated
      rat aorta of Sprague Dawley rats was slightly different. The concentration effect
      curve induced by clonidine was on the right of that induced by phenylephrine,
      with EC50 of 1.5 x 10(-7) M and 3.5 x 10(-4) M for the phenylephrine- and
      clonidine-induced responses, respectively; but the maximal contraction induced by
      clonidine was similar to that of phenylephrine. In the presence of clonidine, the
      concentration effect curve of phenylephrine was shifted to the right. Both the
      phenylephrine- and clonidine-induced contraction were inhibited by prazosin, and
      the EC50 values for prazosin in phenylephrine- and clonidine-induced contraction
      were 1.0 x 10(-8) M and 1.8 x 10(-6) M, respectively. Yohimbine in concentration
      sufficient to antagonize almost completely the effect of phenylephrine was found
      to slightly prevent the effects of clonidine. Further increase of clonidine above
      2 x 10(-3) M, the concentration sufficient to induce the maximal contraction,
      however induced depression of the clonidine-induced contraction, and this
      phenomenon was concentration dependent. Possible explanation of this phenomenon
      was discussed.

PMID- 1359857
TI  - Effect of aspirin on the contractility of aortic smooth muscle in female
      spontaneously hypertensive rats.
AB  - The effects of acetylsalicylic acid (ASA), on aortic smooth muscle contractility
      during hypertension were studied in female SHR and WKY rats. The rats were
      administered two intraperitoneal injections of 10 mg/kg of ASA per week for three
      weeks. Twenty four hours after the last injection the aortic smooth muscles were
      evaluated for generation of active tension in response to KCl, phenylephrine,
      clonidine and norepinephrine. We report that aortic rings from ASA-treated SHR
      animals were more responsive than rings from non-treated SHR female rats. ASA
      treatment of SHR animals restored the contractile response to the level shown by
      non-treated WKY control female rats. The response from aortic rings of ASA
      treated SHR to KCl, phenylephrine and clonidine was essentially similar to the
      response of rings from non-ASA-treated WKY control female rats. We did not
      observe any decrease in the systolic blood pressure during the ASA treatment in
      SHR female rats. These results suggest that acetylsalicylic acid modulates aortic
      smooth muscle contractility either through the metabolites of arachidonic acid or
      through alpha-adrenoceptors.

PMID- 1359858
TI  - Periodontopathic potential of two strains of Porphyromonas gingivalis in
      gnotobiotic rats.
AB  - Germ-free rats were monoinfected with Porphyromonas gingivalis strains 381 or
      A7A1-28 for 42 or 84 days. Both strains induced substantial destruction of
      alveolar bone and soft tissue when compared to non-infected controls, but the
      patterns were different. Strain A7A1-28 was associated with increased activity of
      host collagenase and gelatinase at 42 days, whereas the activity was elevated to
      a lesser extent at 84 days. Strain 381 showed a moderate increase in host
      proteinase activity at 42 days, and this remained unchanged until day 84. Strain
      A7A1-28 was associated with more bone loss than strain 381 by a morphometric
      analysis that detects horizontal bone loss in the maxilla. Strain 381 was
      associated with more bone loss than strain A7A1-28 by a radiographic method that
      detects vertical intrabony defects in the mandible. Infection with one strain
      gave rise to serum and salivary antibodies strongly reactive to the infecting
      strain and moderately reactive to antigens from the other strain. This indicates
      that some antigenic similarity exists between the strains and that there are also
      strain or perhaps serotype differences in antibody responses induced by
      infection. Thus two strains of P. gingivalis differing in antigenicity and
      pathogenicity in the mouse model of the subcutaneous abscess cause substantial
      periodontal destruction in the germ-free rat. The disease pattern is, however,
      different, with strain A7A1-28 inducing mostly horizontal bone loss and strain
      381 mostly vertical.

PMID- 1359860
TI  - Different responses in B cells induced by Porphyromonas gingivalis and
      Fusobacterium nucleatum.
AB  - A phenotypic study had shown that gingival B cells respond differently to two
      periodontopathic bacteria, Porphyromonas gingivalis and Fusobacterium nucleatum.
      Further investigation now shows a reduction in the percentage of Ki-67 + T cells
      in cultures of gingival and peripheral blood mononuclear cells stimulated with P.
      gingivalis for 3 and 6 days, respectively, but no suppression of Ki-67 expression
      in B cells in response to either P. gingivalis or F. nucleatum. Depletion studies
      of cultures of peripheral blood mononuclear cells showed that in the absence of
      CD4 cells, the percentage of CD19+ and CD20+ B cells stimulated with P.
      gingivalis increased after 6 days whereas depletion of CD8 cells resulted in a
      rise in the percentage of F. nucleatum- and P. gingivalis-stimulated B cells,
      although this was not significant in the case of P. gingivalis. Specific antibody
      to P. gingivalis and F. nucleatum was found in culture supernatants of gingival
      but not of peripheral blood mononuclear cells, indicating a possible higher
      frequency of antigen-specific B cells in periodontal lesions. IgG was the
      predominant isotype in both gingival and control peripheral blood cultures,
      followed closely by IgA in gingival cultures. F. nucleatum stimulated higher
      levels of Ig in cultures of peripheral blood mononuclear cells than P. gingivalis
      or cells cultured in medium only, whereas in gingival cell cultures, stimulation
      by P. gingivalis appeared to result in higher levels of IgG. Also Ig was present
      at day 3 in gingival cultures, whereas in the blood cell cultures, Ig was only
      detected at day 6, further suggesting a degree of activation of of gingival B
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359859
TI  - A comparative immunological analysis of the oral mucosa in chronic graft-versus
      host disease and oral lichen planus.
AB  - Oral mucosal biopsies of 12 allogeneic marrow transplant recipients with chronic
      graft-versus-host disease (GVHD) involving the mouth were compared with biopsies
      taken before transplantation. They were also compared with biopsies from
      otherwise healthy patients with oral lichen planus, and with those from a control
      group of normal individuals. Biopsies from chronic GVHD exhibited a low number of
      infiltrating T lymphocytes (CD3 cells) compared with those from oral lichen
      planus, which showed intense cell infiltration (p less than 0.005). The ratio of
      CD4 to CD8 cells in biopsies taken after the manifestation of chronic GVHD
      exhibited no consistent variation compared with those taken before
      transplantation or with biopsies of oral lichen planus. The CD4/CD8 ratio in all
      groups investigated varied between 4:1 and 6:1. The number of natural killer
      cells (CD57), was increased in biopsy specimens taken before transplantation
      compared with the other groups. The frequency of homing receptor, Leu-8 bearing T
      cells was low in the biopsy specimens of all groups, compared with the
      corresponding frequency in peripheral blood (10-45 and 60-90%, respectively; p
      less than 0.001). In the biopsies from chronic GVHD and oral lichen planus the
      number of lymphocytes with transferrin receptors was increased compared with the
      pretransplant and control groups. Virtually no infiltrating cells were carrying
      interleukin-2 receptors (CD25) in any of the groups studied. Langerhans cells
      (CD1) were more frequently found in the specimens from chronic GVHD and oral
      lichen planus than in the pretransplant specimens and the control group (p less
      than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359861
TI  - Pseudo-research in prevention of colorectal cancer and the specialist black hole.

PMID- 1359862
TI  - Effect of the revised CDC case definition of AIDS on the number of AIDS cases in
      the Sydney AIDS Prospective Study.
AB  - We sought to evaluate the potential impact of a proposed revision in the case
      definition of acquired immunodeficiency syndrome (AIDS) (from a clinical case
      definition to one also including subjects with HIV infection who have an absolute
      number of peripheral CD4+ cells of less than 200 x 10(6)/L) among 512 HIV
      seropositive homosexual/bisexual who were reviewed between 1984 and 1991.
      According to the current case definition, 151 (30%) of 512 at-risk subjects
      developed AIDS between 1984 and August 1, 1991. Of the 361 at-risk subjects who
      were not classified as AIDS by the current definition, 47 (13%; 95% CI 9-17%)
      were classified as AIDS according to the revised definition. The median time to
      development of AIDS according to the revised definition was 288 weeks and that
      according to the current definition was 338 weeks. Data on clinical status were
      available for 34 of the new cases at the time of their diagnosis according to the
      proposed case definition: 16 (47%) of these were asymptomatic, 10 (29%) had
      persistent generalised lymphadenopathy and eight had minor infectious diseases.
      Of the 151 cases diagnosed according to the current definition, 78 (52%) had an
      antecedent CD4+ cell count that met the criteria for AIDS under the revised
      definition a median of 59 weeks before their diagnosis according to the current
      definition. These data indicate an appreciable increase in the number of cases of
      AIDS in this cohort when the revised case definition was applied. These findings
      have important implications for the surveillance, and for the clinical monitoring
      and treatment, of patients with HIV disease in Australia.

PMID- 1359863
TI  - 5-Fluorouracil-induced pseudoporphyria.

PMID- 1359864
TI  - Asthma mortality and inhaled beta agonist therapy.

PMID- 1359865
TI  - Sulphasalazine induced aplastic anaemia.

PMID- 1359866
TI  - Australian Association of Neurologists, annual scientific meeting. Melbourne,
      Victoria, 1-3 June 1992. Abstracts.

PMID- 1359867
TI  - Experience with the pulsed dye laser in management of ureteric calculi.
AB  - Pulsed dye laser lithotripsy is a recently developed technique for the management
      of urinary calculi. This article reports the results of treatment of a cohort of
      patients managed with this technology. Post-treatment bed stay was generally less
      than 48 h, narcotic analgesia was not regularly required, and no significant post
      treatment complications were encountered. This treatment appeared to complement
      an existing extracorporeal shockwave lithotripsy (ESWL) service at St Vincent's
      Hospital and may offer a financial advantage in the treatment of patients with
      urinary calculi.

PMID- 1359868
TI  - Open cholecystectomy: a control group for comparison with laparoscopic
      cholecystectomy.
AB  - Laparoscopic cholecystectomy is rapidly becoming accepted as the best method for
      the treatment of symptomatic cholelithiasis. Randomized clinical trials comparing
      laparoscopic cholecystectomy with open cholecystectomy are unlikely to be
      performed. In order to compare these two operations, surgeons need an historical
      control group of patients who have undergone a conventional open cholecystectomy.
      The aim of this study was to document a control group of patients having an open
      cholecystectomy and compare them with patients having a laparoscopic
      cholecystectomy. This was achieved by a retrospective study of all patients who
      had an open cholecystectomy from January 1985 to December 1989. Four hundred and
      fifty-seven patients, 345 women and 112 men, had a cholecystectomy. Exploration
      of the common bile duct (ECBD) was performed in 59 (12.5%) cases. The mean
      operative duration was 73 min for cholecystectomy and 118 min for cholecystectomy
      and ECBD. The shortest mean postoperative stay was for an elective
      cholecystectomy (5.3 days) and the longest mean postoperative stay was for urgent
      admissions requiring ECBD (12.0 days). Operative dissection was difficult in
      14.1% of elective cases and 51.8% of urgent cases. Ninety-seven (19.5%) patients
      had an additional procedure, unrelated to cholelithiasis, at the same operation;
      44 did not require laparotomy, 31 had interval appendectomies, and 22 other cases
      required laparotomy in order to perform the additional procedure. All but one
      patient required postoperative narcotic analgesia. The mean duration of narcotic
      analgesia was 2.3 days. The complication rate was 35.2% for cholecystectomy and
      62.5% for ECBD. If pulmonary atelectasis is excluded as a complication, these
      complication rates fell to 6.8% and 20.1%, respectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1359869
TI  - Hypokalaemic episodic polymyopathy in cats fed a vegetarian diet.
AB  - A previously undocumented hypokalaemic condition with a cyclical nature,
      comprising acute bouts of polymyopathy followed by spontaneous recoveries, is
      described in the cat. Cats being fed a high protein vegetarian diet developed
      recurrent episodes of polymyopathy, characterised by ventroflexion of the head
      and neck, stiff forelimb gait, lateral head-resting and generalised muscle
      weakness. Plasma potassium concentrations (mean +/- standard deviation) were
      reduced from 3.28 +/- 0.33 mmol/l at the beginning of the experiment to 2.45 +/-
      0.24 mmol/l during bouts of myopathy. This hypokalaemia was associated with
      increased creatine kinase activities indicative of muscle damage, and decreased
      urinary potassium concentrations, and was caused by insufficient dietary
      potassium. Cats that received the same diet supplemented with potassium did not
      develop hypokalaemic polymyopathy. Spontaneous recoveries of affected cats were
      not associated consistently with increases in plasma potassium concentrations.
      Plasma taurine concentrations decreased and glutamic acid increased markedly in
      all cats fed the experimental diet. There was no evidence of thiamin deficiency
      associated with the high glutamic acid intake. Veterinarians should be aware that
      hypokalaemic cats, and in particular those on potassium-deficient diets, may show
      cyclical disease with episodes of polymyopathy recurring after periods of
      spontaneous clinical recovery. This condition in cats may be a useful animal
      model for familial hypokalaemic periodic paralysis in humans.

PMID- 1359871
TI  - Restriction fragment length variants in the marsupial Sminthopsis crassicaudata.
AB  - A fully pedigreed colony of the dasyurid marsupial Sminthopsis crassicaudata has
      provided material for establishing two panels of DNA samples: a broadbased test
      panel and a two-generation family panel. These have been used to search for
      genetic markers in the form of restriction fragment length variants. The
      molecular probes--pSG-2H, a region of the S. crassicaudata embryonic beta-globin
      gene; pB8.BS, a region of the human ubiquitin gene, and p3-21a1:1, a region of
      the processed pseudogene of phosphoglycerate kinase-1 of the macropodid marsupial
      Macropus robustus--were hybridized to Southern blots of EcoR1-digested DNA from
      the panels. Analysis of these blots when probed with pSG-2H provided evidence of
      two alleles segregating at a single EcoR1 site. Analysis of the same blots when
      probed with pB8.BS suggested allelic variation at two closely linked EcoR1 sites.
      Probing the blots with p3-21a1:1 produced a complex pattern of bands resembling
      DNA fingerprints. The presence of a 12.3-kb band was found to conform to a simple
      autosomal dominant mode of inheritance. Analysis of the family data, for each
      probe, revealed no significant departure from Mendelian inheritance. This work
      has provided additional genetic markers that will enhance the use of S.
      crassicaudata as a model marsupial species and has demonstrated that a high level
      of genetic variability has been maintained in the marsupial colony.

PMID- 1359870
TI  - Mapping of the mouse bilirubin UDP-glucuronosyltransferase gene (Gnt-1) to
      chromosome 1 by restriction fragment length variations.
AB  - Restriction endonuclease fragment length variations (RFLVs) were detected by
      using a rat cDNA probe for the bilirubin UDP-glucuronosyltransferase (UDPGT) gene
      between two mouse strains, 129/Sv and MOL-MIT. RFLVs of the gene were found by
      EcoRI and PvuII digestions. From linkage analyses of the three-point cross test
      using Elo and En-1 as marker genes, the bilirubin UDPGT gene was mapped at
      position 37 on chromosome 1. Bilirubin and phenol UDPGTs have been suggested to
      be expressed by a single gene by alternative splicing in human and rat. The mouse
      bilirubin UDPGT gene was named Gnt-1.

PMID- 1359872
TI  - A molecular genetic linkage map of mouse chromosome 10, including the Myb, S100b,
      Pah, Sl, and Ifg genes.
AB  - Restriction endonuclease fragment length variations (RFLV) on mouse chromosome 10
      were detected in four genes, namely, the Myb protooncogene (Myb) and the genes
      for S100 beta protein (S100b), phenylalanine hydroxylase (Pah), and interferon
      gamma (Ifg). RFLV were found in restriction patterns generated with BamHI for
      Myb, in those generated with BglII for S100b, in those generated with EcoRV for
      Pah, and in those generated with TaqI for Ifg. A multipoint backcross was carried
      out by the mating (129/Sv-Sl/+ x MOL-MIT)F1 x 129/SvJ(-)+/+. The Sl mutation has
      phenotypic effects which include deficiencies in pigment cells, germ cells, and
      blood cells. The following order of genes was derived from the results of the
      multipoint backcross, with distances between genes in parentheses: centromere-
      Myb--(34.9 cM)--S100b--(8.5 cM)--Pah--(8.5 cM)--Sl--(12.3 cM)--Ifg--telomere.
      Most laboratory strains and two strains of Mus musculus domesticus of wild origin
      carry the Myba, S100a, Paha, and Ifga alleles. In contrast, a strain of M. m.
      musculus, two strains of M. m. yamashinai, and two strains of M. m. molossinus
      carry the Mybb, S100b, Pahb, and Ifgb alleles. Other strains of wild origin carry
      various combinations of these alleles.

PMID- 1359873
TI  - A restriction fragment length polymorphism (RFLP) locus of rat (Rattus
      norvegicus) linked to the Cs-1 locus of rat linkage group XIII.
AB  - A novel restriction fragment length polymorphism (RFLP) in inbred rats was
      revealed by Southern blot analysis with a clone arbitrarily chosen from a rat
      genomic library as a probe. A clone named alpha 403 showed interstrain variations
      in the length of the EcoRI and HindIII fragments. The EcoRI fragments were either
      0.7 or 3 kb, those of HindIII were either 4.5 or 5 kb, and three types were
      identified as combinations of those fragments in 20 inbred rat strains. These
      types segregated in backcross progeny as codominant alleles. The locus for the
      RFLP was thus named A403. Analysis of linkage between the RFLP locus and 13 other
      loci reveal that the A403 locus was closely linked to the Cs-1 locus (15 +/-
      5.2%), which belongs to rat linkage group XIII.

PMID- 1359874
TI  - Uracil-DNA glycosylases preferentially excise mispaired uracil.
AB  - We have investigated the substrate specificity of human, viral and bacterial
      uracil-DNA glycosylases employing as substrate double-stranded oligonucleotides
      containing in the same position of the 5'-32P-labelled strand an uracil residue
      facing, on the complementary strand, guanine (mimicking cytosine deamination) or
      adenine (mimicking dUTP misincorporation). The enzyme removal of uracil was
      monitored and quantified by the generation of alkali-sensitive apyrimidinic
      sites. All three uracil-DNA glycosylases excise uracil from mispaired
      oligonucleotides (U/G) more efficiently than from paired oligonucleotides (U/A).
      The enzymes also remove uracil from single-stranded oligonucleotide with an
      efficiency similar to that observed with U/A paired oligonucleotide. The
      efficient recognition of U/G mispair by uracil-DNA glycosylase is important in
      minimizing miscoding transcripts and C/G-->T/A transitions in proliferating
      cells.

PMID- 1359875
TI  - Tissue- and developmental-stage-specific methylation in the two kidney promoters
      of the rat gamma-glutamyl transpeptidase gene.
AB  - We have investigated, using DNA methylation patterning, the site-specific
      methylation of promoters I and II of the rat gamma-glutamyl transpeptidase gene.
      This analysis was done in fetal, newborn and adult rat kidney, in which promoters
      I and II are progressively active during development, as well as in rat liver,
      which never expresses mRNAs from these two promoters. During kidney development,
      a progressive demethylation occurs in the promoter I and II region, specially at
      the level of the most proximal MspI site of promoter II. A progressive
      reorganization of the methylated sites within the 5' end of the gene also occurs
      during liver development.

PMID- 1359876
TI  - Assay method for monitoring the inhibitory effects of antimetabolites on the
      activity of inosinate dehydrogenase in intact human CEM lymphocytes.
AB  - A rapid and convenient method has been developed to monitor the inhibition of
      inosinate (IMP) dehydrogenase by antimetabolites in intact human CEM lymphocytes.
      This method is based on the determination of 3H release from [2,8-3H]hypoxanthine
      ([2,8-3H]Hx) or [2,8-3H]inosine ([2,8-3H]Ino). The validity of this procedure was
      assessed by evaluating IMP dehydrogenase inhibition in intact CEM cells by the
      well-known IMP dehydrogenase inhibitors ribavirin, mycophenolic acid and
      tiazofurin. As reference materials, several compounds that are targeted at other
      enzymes in de novo purine nucleotide anabolism (i.e. hadacidine, acivicin) or
      catabolism (i.e. 8-aminoguanosine, allopurinol) were evaluated. There was a
      strong correlation between the inhibitory effects of the IMP dehydrogenase
      inhibitors (ribavirin, mycophenolic acid, tiazofurin) on 3H release from [2,8
      3H]Hx and [2,8-3H]Ino in intact CEM cells and their ability to decrease
      intracellular GTP pool levels. The other compounds (hadacidine, acivicin, 8
      aminoguanosine, allopurinol) had no marked effect on 3H release from [2,8-3H]Hx.
      Using this method, we demonstrated that the novel ribavirin analogue, 5-ethynyl-1
      beta-D-ribofuranosylimidazole-4-carboxamide, is a potent inhibitor of IMP
      dehydrogenase in intact cells.

PMID- 1359877
TI  - A protonated histidine residue in a phosphorylation site for cyclic AMP-dependent
      protein kinase. Comparison of a synthetic peptide with the exposed linking region
      in the multienzyme polypeptide CAD.
AB  - The multienzyme polypeptide CAD is phosphorylated at two sites by cyclic AMP
      (cAMP)-dependent protein kinase. Site 2 has two interesting features: it is
      located in a 'linking region' between two discretely folded enzyme domains, and a
      histidine, instead of the more usual arginine, is found three positions N
      terminal to the phosphorylated serine. A synthetic peptide corresponding to the
      sequence around site 2 has an extended or random structure in solution, and the
      proton n.m.r. chemical shift of the histidine residues can be titrated against pH
      in the range 6.0-8.0. The peptide is phosphorylated more rapidly by cAMP
      dependent protein kinase at lower pH values, indicating that the protonated
      histidine side chain corresponds to the arginine in the consensus recognition
      sequence for the kinase. Kemptide, a specific synthetic substrate for the kinase,
      was phosphorylated with a higher affinity and at a similar rate at all pH values.
      CAD was a better substrate than the synthetic peptide, and labelling was not
      affected by the pH of the incubation conditions. The results indicate that the
      phosphorylation site in the interdomain linker is sufficiently exposed to the
      solvent to ensure accessibility to the kinase, but that secondary or tertiary
      structure in the intact protein allows the histidine residue to remain protonated
      at physiological pH and enhances recognition of the phosphorylatable serine
      residue.

PMID- 1359878
TI  - 1H-and 13C-n.m.r. spectroscopy of 2-oxo-3-deoxy-D-glycero-D- galactononulosonic
      acid-containing oligosaccharide-alditols bearing Lewis X, Lewis Y and A-Lewis Y
      determinants isolated from the jelly coat of Pleurodeles waltl eggs.
AB  - Three acidic oligosaccharide-alditols carrying Lewis X, Lewis Y and A-Lewis Y
      determinants were isolated from the jelly coat of Pleurodeles waltl eggs. These
      compounds possess the following structures. Gal beta 1-4(Fuc alpha 1-3)GlcNAc
      beta 1-3[2-oxo-3-deoxy-D- glycero-D-galactononulosonic acid (KDN)alpha 2-6]
      GalNAc-ol; Fuc alpha 1-2Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3(KDN alpha 2-6)
      GalNAc-ol and Fuc alpha 1-2(GalNAc alpha 1-3)Gal beta 1-4(Fuc alpha 1-3)GlcNAc
      beta 1-3(KDN alpha 2-6)GalNAc-ol. The complete 1H-n.m.r.-spectrum assignment for
      the three compounds and the 13C-n.m.r. analysis of the A-Lewis Y determinant
      containing heptasaccharide are reported.

PMID- 1359879
TI  - The structural basis for the electrophoretic isoforms of normal and variant human
      platelet arylsulphatase A.
AB  - Human platelet arylsulphatase A (ASA) exhibits a multiple banding pattern when
      examined by PAGE. The isoform pattern (IVa) of the enzyme obtained from normal
      subjects differs from variants (IIIa, IIIb, IVb) which are primarily found in
      alcoholic patients. Alkaline phosphatase and endo-N-acetylglucosaminidase H
      treatments, as well as ion-exchange chromatography, demonstrate that the isoforms
      of ASA arise because of charge heterogeneity caused by phosphoglycan moieties.
      The isoform with the slowest mobility in PAGE lacks phosphate substituents. Based
      upon mannose-6-phosphate-receptor affinity chromatography it can be concluded
      that most, if not all, of the enzyme-linked phosphate is in the form of 6-O
      phospho-D-mannosyl units. Lectin affinity chromatography and peptide-N
      glycosidase F treatment followed by SDS/PAGE and Western-blot analysis indicate
      that normal platelet ASA contains two oligomannose and/or hybrid glycan moieties
      of which one, or both, possess a 6-O-L-fucosyl substituent on the asparagine
      linked N-acetylglucosamine residue. Comparative analysis indicates that the
      variant IIIa and IIIb types of ASA differ from the IVa ASA with regard to the
      level of glycan phosphorylation and glycan structure, as well as the polypeptide
      structure.

PMID- 1359880
TI  - Site-directed mutagenesis at aspartate and glutamate residues of xylanase from
      Bacillus pumilus.
AB  - To elucidate the reaction mechanism of xylanase, the identification of amino
      acids essential for its catalysis is of importance. Studies have indicated the
      possibility that the reaction mechanism of xylanase is similar to that of hen's
      egg lysozyme, which involves acidic amino acid residues. On the basis of this
      assumption, together with the three-dimensional structure of Bacillus pumilus
      xylanase and its amino acid sequence similarity to other xylanases of different
      origins, three acidic amino acids, namely Asp-21, Glu-93 and Glu-182, were
      selected for site-directed mutagenesis. The Asp residue was altered to either Ser
      or Glu, and the Glu residues to Ser or Asp. The purified mutant xylanases D21E,
      D21S, E93D, E93S, E182D and E182S showed single protein bands of about 26 kDa on
      SDS/PAGE. C.d. spectra of these mutant enzymes show no effect on the secondary
      structure of xylanase, except that of D21E, which shows a little variation.
      Furthermore, mutations of Glu-93 and Glu-182 resulted in a drastic decrease in
      the specific activity of xylanase as compared with mutation of Asp-21. On the
      basis of these results we propose that Glu-93 and Glu-182 are the best candidates
      for the essential catalytic residues of xylanase.

PMID- 1359881
TI  - Translation rates of isolated liver mitochondria under conditions of hepatic
      mitochondrial proliferation.
AB  - The hepatic mitochondrial content is increased in rats by treatment with the
      hypolipidaemic drug clofibrate and by administration of the cobalamin analogue
      hydroxycobalamin[c-lactam] (HCCL), an inhibitor of hepatic L-methylmalonyl-CoA
      mutase activity. As a first step in defining the mechanisms regulating liver
      mitochondrial contents in these models, the current studies were designed to test
      the hypothesis that hepatic mitochondrial proliferation is associated with
      enhanced translation rates of mitochondrial DNA gene products. Incorporation of
      [35S]methionine and [3H]leucine into protein was quantified in mitochondria
      isolated from control, clofibrate- and HCCL-treated rats. Use of multiple amino
      acid substrate concentrations permitted the maximal rate of translation (Vmax.)
      to be determined independent of endogenous amino acid concentrations. The Vmax.
      for methionine incorporation was not different in the models evaluated (0.062,
      0.057 and 0.061 pmol/min per mg of mitochondrial protein in control, clofibrate-
      and HCCL-treated rats respectively). Similar results were obtained for leucine
      incorporation when absolute fractional radiolabel incorporation rates were
      analysed and when conventional Lineweaver-Burk analysis was employed. These
      results demonstrate no change in the intrinsic capacity of mitochondrial
      translation in these two models of hepatic mitochondrial proliferation.

PMID- 1359882
TI  - Stimulation of neutrophil adhesion by antibodies recognizing CD15 (Le(X)) and
      CD15-expressing carcinoembryonic antigen-related glycoprotein NCA-160.
AB  - The carbohydrate antigen, CD15 (Le(X)), and its sialylated derivative have
      recently been shown to be involved in the binding of neutrophils to the
      endothelial lectins, E-selectin and P-selectin. Neutrophil NCA-160, a
      carcinoembryonic antigen (CEA)-related glycoprotein, is the major carrier of
      CD15, which is also expressed on the common beta 2 chain of leucocyte integrins.
      Rabbit IgG antibodies directed against CEA, which cross-react with neutrophil
      NCAs, increase the adhesion of neutrophils to plastic. This effect is also
      observed with F(ab')2 and Fab antibody fragments and a monoclonal antibody (mAb)
      recognizing the same antigen. Anti-CD15 mAbs inhibit adhesion at higher
      concentrations, but augment adhesion at lower concentrations. Anti-CEA and anti
      CD15 antibodies cause the homotypic adhesion of neutrophils demonstrable by light
      microscopy and flow cytometry. Anti-(integrin beta 2 chain) mAbs inhibit both
      adhesion to plastic and homotypic adhesion. These results suggest that binding of
      ligand to NCA-160 is able to trigger neutrophil adhesion events which have been
      shown to be integrin mediated. Anti-CD15 mAbs do not, however, induce a
      respiratory burst from neutrophils.

PMID- 1359884
TI  - Retinoic acid and development of the central nervous system.
AB  - We consider the evidence that RA, the vitamin A metabolite, is involved in three
      fundamental aspects of the development of the CNS: 1) the stimulation of axon
      outgrowth in particular neuronal sub-types; 2) the migration of the neural crest;
      and 3) the specification of rostrocaudal position in the developing CNS
      (forebrain, midbrain, hindbrain, spinal cord). The evidence we discuss involves
      RA-induction of neurites in cell cultures and explants of neural tissue; the
      teratological effects of RA on the embryo's nervous system; the observation that
      RA can be detected endogenously in the spinal cord; and the fact that the
      receptors and binding proteins for RA are expressed in precise domains and
      neuronal cell types within the nervous system.

PMID- 1359883
TI  - CD3 and CD2 antigen-mediated CD3 gamma-chain phosphorylation in permeabilized
      human T cells. Regulation by cytosolic phosphatases.
AB  - The role of cytosolic and membrane-associated phosphatases in regulating
      dephosphorylation of the CD3 antigen gamma-chain has been investigated using
      streptolysin-O-permeabilized T lymphoblasts and Jurkat T leukaemia cells.
      Permeabilization of T cells caused a rapid extrusion of cytosolic type 2A
      phosphatases, but a membrane-associated phosphorylase phosphatase activity
      remained inside the cells. This activity had the properties characteristic of
      type 2A phosphatases, being resistant to inhibition by type 1 phosphatase
      inhibitors, though it was inhibited in a time-dependent manner by ATP or by non
      hydrolysable ATP analogues, but not by GTP, CTP, ITP or PPi. The membrane
      associated type 2A phosphatase in permeabilized cells did not dephosphorylate the
      CD3 antigen gamma-chain, suggesting that cytosolic phosphatases dephosphorylate
      the gamma-chain in situ. Cross-linking the CD2 and CD3 antigens with a bivalent
      monoclonal antibody in the absence of cytosolic phosphatases induced marked
      phosphorylation of the CD3 gamma-chain, immunoprecipitated using a novel gamma
      chain peptide analogue directed antiserum (TG1). Phosphorylation was inhibited by
      a protein kinase C (PKC) pseudosubstrate inhibitor, indicating that CD2/CD3
      induced gamma-chain phosphorylation is a PKC-mediated event. Activation of T
      cells either with phorbol 12,13-dibutyrate or by CD2-CD3 cross-linking caused
      [32P]Pi incorporation into the same gamma-chain Ser residues. The site-mapping
      data suggested that PKC in situ may incorporate phosphate at the CD3 gamma-chain
      Ser-123 and Ser-126 residues, but that phosphate is rapidly lost from Ser-123 by
      cytosolic phosphatase action. Our findings underline the importance of the dual
      actions of kinases and phosphatases as potential regulators of T cell antigen
      receptor complex function.

PMID- 1359885
TI  - Cloning of the genes for excitatory amino acid receptors.
AB  - Glutamate is the major excitatory neurotransmitter in the mammalian brain, with
      receptors on every neuron in the central nervous system; it has major roles in
      fast synaptic transmission and in the establishment of certain forms of memory.
      More than 20 years ago Olney and his colleagues described the 'Excitotoxic
      Hypothesis' which postulates that, in addition to its normal function in the
      healthy brain, glutamate can kill neurons by prolonged, receptor-mediated
      depolarization resulting in irreversible disturbances in ion homeostasis.
      Therefore, glutamate is a two-edged sword; in certain undefined, adverse
      conditions it undergoes a transition from neurotransmitter to neurotoxin. Its
      toxicity has been implicated in the death of neurons in ischemia, epilepsy, and
      the neurodegenerative disorders such as Alzheimer's, Huntington's, and
      Parkinson's disease. Recent advances in the molecular cloning of the genes for
      the glutamate family of receptors has revealed a plethora of receptor subtypes
      and an unexpected level of complexity in the mechanisms of receptor expression
      and function.

PMID- 1359887
TI  - Purification of lipoxygenase and hydroperoxide dehydrase in flaxseeds:
      interaction between these enzymatic activities.
AB  - We have purified two enzymic activities from flaxseed acetone powder: a
      lipoxygenase and a hydroperoxide dehydrase. The lipoxygenase activity belongs to
      an iron-containing protein having a molecular weight of 130 kDa which, upon
      incubation with alpha-linolenic acid, forms 13-hydroperoxy-9(Z), 11(E), 15(Z)-
      octadecatrienoic acid. The hydroperoxide dehydrase (a 55 kDa protein) metabolizes
      this hydroperoxide to an allene oxide which in turn is spontaneously hydrolyzed
      to alpha- and gamma-ketols. Relationships between these two enzymes were studied
      and results suggest an inhibition of the lipoxygenase by hydroperoxide dehydrase.

PMID- 1359888
TI  - Ursodeoxycholic acid-dependent activation of the glucocorticoid receptor.
AB  - Therapeutic effectiveness of ursodeoxycholic acid (UDCA) for primary biliary
      cirrhosis strongly indicates that UDCA possesses immunomodulatory activities. In
      order to further investigate mechanical background of such UDCA action, we first
      asked whether UDCA modulates glucocorticoid-mediated signal transduction. Using
      electrophoretic mobility-shift assay, we demonstrated that treatment with UDCA
      promoted the specific complex formation between the cytosol protein and the
      glucocorticoid-response element DNA in a dose-dependent fashion in vitro, and
      also nuclear translocation of the glucocorticoid receptor (GR) in vivo. Gene
      transfer experiments revealed that UDCA induced cellular CAT activities in a GR
      dependent fashion, but rather weakly as compared to synthetic glucocorticoid
      dexamethasone.

PMID- 1359889
TI  - Molecular cloning of a truncated isoform of the human follicle stimulating
      hormone receptor.
AB  - Northern blot hybridization of human testicular poly (A)+ RNA to a human follicle
      stimulating hormone receptor probe revealed the existence of multiple mRNA
      transcripts. In order to investigate whether alternative splicing of the receptor
      occurs in the human testis we amplified the extracellular and the transmembrane
      domain of the human testicular follicle stimulating hormone receptor by reverse
      transcription polymerase chain reaction and subcloned the resulting DNA
      fragments. Sequence analysis of the recombinant clones revealed the existence of
      a truncated isoform of the human follicle stimulating hormone receptor which is
      spliced through a cassette exon mode without a change in the open reading frame,
      thereby deleting exon IX from the coding region of the receptor.

PMID- 1359886
TI  - Selective assays for thymidine kinase 1 and 2 and deoxycytidine kinase and their
      activities in extracts from human cells and tissues.
AB  - Human cells salvage pyrimidine deoxyribonucleosides via 5'-phosphorylation which
      is also the route of activation of many chemotherapeutically used nucleoside
      analogs. Key enzymes in this metabolism are the cytosolic thymidine kinase (TK1),
      the mitochondrial thymidine kinase (TK2) and the cytosolic deoxycytidine kinase
      (dCK). These enzymes are expressed differently in different tissues and cell
      cycle phases, and they display overlapping substrate specificities. Thymidine is
      phosphorylated by both thymidine kinases, and deoxycytidine is phosphorylated by
      both dCK and TK2. The enzymes also phosphorylate nucleoside analogs with very
      different efficiencies. Here we present specific radiochemical assays for the
      three kinase activities utilizing analogs as substrates that are by more than 90
      percent phosphorylated solely by one of the kinases; i.e. 3'-azido-2',3'
      dideoxythymidine (AZT) as substrate for TK1, 1-beta-D-arabinofuranosylthymidine
      (AraT) for TK2 and 2-chlorodeoxyadenosine (CdA) for dCK. We determined the
      fraction of the total deoxycytidine and thymidine phosphorylating activity that
      was provided by each of the three enzymes in different human cells and tissues,
      such as resting and proliferating lymphocytes, lymphocytic cells of leukemia
      patients (chronic lymphocytic, chronic myeloic and hairy cell leukemia), muscle,
      brain and gastrointestinal tissue. The detailed knowledge of the pyrimidine
      deoxyribonucleoside kinase activities and substrate specificities are of
      importance for studies on chemotherapeutically active nucleoside analogs, and the
      assays and data presented here should be valuable tools in that research.

PMID- 1359890
TI  - Gene expression of proliferating cell nuclear antigen in rat brain.
AB  - Proliferating cell nuclear antigen (PCNA), a non-histone nuclear protein which is
      preferentially present in rapidly growing cells, was found to express at a
      significant level in both cerebellum and cerebrum of adult rat brain. Analysis
      with in situ hybridization did not reveal any region in the brain which is
      particularly abundant in PCNA transcripts. However, it was noted that the cell
      bodies of Purkinje cells contained PCNA transcripts. The Purkinje cells are nerve
      cells of cerebellum and generally thought to be non-proliferative. Regardless the
      high level of PCNA mRNA in the rat brain, the PCNA protein was not detected in
      the tissue by immunostaining or immunoblotting analysis. This suggests that
      regulation of PCNA gene expression in brain may be at translational level.

PMID- 1359891
TI  - Dipeptidylpeptidase IV in human leukemic B- and T-cells.
AB  - Dipeptidylpeptidase IV (DPP-IV) activity in lymphoid cells of patients with
      various lymphoproliferative diseases has been assayed. The enzyme activity was
      detected in lysates of all leukemic T- and B-cells studied. High DPP-IV activity
      levels (5-7 fold higher than those in mature Th and Ts) were found in T-cells
      with phenotypes corresponding either to the early thymic stages of maturation, or
      to activated T-lymphocytes, or to some atypic T-cells. In most leukemic B-cells
      with phenotypes of mature and late B-lymphocytes, the DPP-IV activity was lower
      than in mature T-cells; however, in some B-cells carrying the activation markers
      CD 25 and CD 30 the activity was rather high. High DPP-IV activity was seen in
      the majority of leukemic B-cells expressing CD 25 (87%) and CD 11c (82%)
      antigens. Experiments with intact cells have shown that DPP-IV is present in the
      plasma membrane of leukemic B- and T-cells studied. Thus DPP-IV cannot be
      considered as a marker of activated T-cells alone because a significant DPP-IV
      activity was also detected in a number of activated leukemic B-cells and in early
      T-cells.

PMID- 1359893
TI  - Determination of pipamperone in human plasma by high performance liquid
      chromatography.
AB  - A sensitive and reproducible high performance liquid chromatographic method was
      developed for the determination of pipamperone (1'-[4-(4-fluorophenyl)-4
      oxobutyl]-[1,4'-bipiperidine]-4'- carboxamide, Dipiperon, CAS 1893-33-0) in
      plasma samples. Pipamperone and its internal standard (piritramide or 1'-(3-cyano
      3,3-diphenylpropyl)-[1,4'-bipiperidine]-4'-carbo xamide) were extracted from
      alkalinized plasma by liquid-liquid extraction and analysed on a reversed-phase
      (C18) column. In order to reduce analysis time, a gradient elution technique was
      applied. Chromatographic peaks were quantified by UV detection at two
      wavelengths. The method has a detection limit of 2 ng/ml, it proved to have good
      accuracy and precision, and was linear in the range of 2 to 400 ng/ml. The assay
      was extensively applied to study the pharmacokinetics in man after oral
      administration of the drug.

PMID- 1359894
TI  - Placental transfer of the anxiolytic beta-carboline abecarnil in rabbit.
AB  - The placental transfer of abecarnil (isopropyl 6-(benzyloxy)-4- (methoxymethyl)9H
      pyrido(3,4-b)indole-3-carboxylate, ZK 112 119, CAS 11184-1-85-1) was studied in
      the rabbit after i.v. injection of 0.1 mg/kg and oral dosing of 10 mg/kg using
      14C-labeled drug and HPLC with fluorescence detection for measurement of the
      unchanged drug. Abecarnil easily passed the placental barrier and achieved high
      concentrations in the fetus. The concentration ratio C(fetus)/C(dam plasma) was
      24 +/- 12 for all animals and time points. Metabolites were not able to cross the
      placental barrier to the same extent as the unchanged drug (ratio 1 +/- 2). The
      time courses of drug concentration and total radioactivity in the fetus were
      parallel to the respective time courses in the dams plasma. Accumulation of drug
      and metabolites upon multiple dosing, therefore, should not differ from that
      observed in the dam.

PMID- 1359892
TI  - [Modification of melanostatin].

PMID- 1359896
TI  - Reduction of adverse effects of indomethacin by anti-allergic drugs in rat
      stomachs.
AB  - This study was designed to elucidate the role of leukotrienes (LT) in
      indomethacin-induced gastric ulcers in relation to effects of clinically
      available anti-allergic drugs, azelastine (Azeptin, CAS 58581-89-8) and oxatomide
      (CAS 60607-34-3). Azelastine (2 mg/kg) or oxatomide (30 mg/kg) was administered
      intragastrically once 15 min before intragastrical administration of 12 mg/kg of
      indomethacin. Mucosal prostaglandins (PGs) and LTs were measured by high
      performance liquid chromatography (HPLC). In the control rats, 4 kinds of PGs,
      i.e., 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and PGD2, were detected in gastric
      mucosa, but no LT was detected. Administration of indomethacin caused severe
      gastric ulcers (lesion scores; 31.2 +/- 11.1 mm), and all prostaglandins were
      diminished completely. In contrast, LTC4 and LTD4 (peptide-LTs) were detected and
      the sum of their levels was 18.5 +/- 7.1 ng/g tissue. Irrespective of
      indomethacin administration, lesion scores were remarkably reduced in rats
      treated with azelastine or oxatomide (17.0 +/- 8.1 and 16.0 +/- 8.0,
      respectively). Azelastine and oxatomide treatment did not improve mucosal PG
      levels, however, both drugs reduced significantly increases in peptide-LT level,
      9.3 +/- 4.6 and 8.6 +/- 4.4, respectively. These results suggest that increases
      in mucosal LT levels are also involved in the formation of indomethacin-induced
      gastric ulcers. Combined therapy using anti-allergic drugs and non-steroidal anti
      inflammatory drugs might be recommended.

PMID- 1359895
TI  - Evaluation of the alpha-adrenoceptor antagonistic action of berberine in isolated
      organs.
AB  - The selectivity and specificity of berberine (CAS 2086-83-1) for alpha
      adrenoceptor subtypes have been studied. alpha 1-Adrenoceptors were investigated
      in rat and rabbit aorta and alpha 2-adrenoceptors in guinea-pig ileum
      preparations. Subtype selectivity was then assessed by calculating the
      selectivity ratios from Ke (equilibrium constant) values. Berberine was found to
      be more potent for the postsynaptic alpha 1-adrenoceptors than presynaptic alpha
      2-adrenoceptors. The selectivity ratios were 1.9 and 3.1 for rabbit and rat
      aorta, respectively. In the rabbit aorta, responses to norepinephrine and
      phenylephrine were both inhibited by berberine with lower affinity than that in
      the rat aorta. The pA2 values for berberine obtained from the norepinephrine and
      phenylephrine experiments were also found significantly different in rat aorta.
      However, similar pA2 values were found in rabbit aorta for those agonists.

PMID- 1359897
TI  - Cellular pattern of multidrug-resistance gene expression during chemical
      hepatocarcinogenesis in the rat.
AB  - Increased expression of multidrug-resistance (mdr) gene transcripts and of the
      encoded protein, P-glycoprotein, is found in many types of tumors. The biological
      significance of mdr overexpression during the stepwise process of neoplastic
      development, however, is not well understood. To assess the possible significance
      of mdr overexpression in carcinogenesis, we examined the cellular distributions
      of both mdr gene transcripts and P-glycoprotein during hepatocarcinogenesis
      induced in rats by the Solt-Farber protocol and then compared them to the
      distributions of the placental form of glutathione S-transferase (GST-P), a known
      marker of preneoplastic and neoplastic lesions in the liver. In situ
      hybridization and immunohistochemical techniques were employed. Neither mdr
      transcripts nor P-glycoprotein was expressed in oval cells that appeared early in
      the carcinogenic process. GST-P was strongly expressed in the early focal
      lesions, whereas the levels of mdr transcripts and P-glycoprotein expressed were
      low and heterogeneous. Expression of mdr transcripts and P-glycoprotein was
      increased and became more uniform in hyperplastic nodules and carcinomas,
      although considerable heterogeneity of expression was still found, particularly
      at the nodular stage. These data suggest that increased expression of mdr is
      associated with later stages of neoplastic development in the liver. Furthermore,
      that no chemical treatment of the animals was employed when the expression of mdr
      was increasing in the preneoplastic and neoplastic lesions suggests that the
      enhanced mdr expression is intrinsic to the carcinogenic process.

PMID- 1359898
TI  - Neurobiology of motivation: double dissociation of two motivational mechanisms
      mediating opiate reward in drug-naive versus drug-dependent animals.
AB  - Separate brain manipulations double dissociate two motivational mechanisms
      underlying the rewarding effects of opiates. Lesions of the brain stem tegmental
      pedunculopontine nucleus block the rewarding properties of morphine in drug
      naive, but not in drug-dependent, rats. Neuroleptics (which block the action of
      the neurotransmitter dopamine) abolished opiate motivational effects in drug
      dependent, but not in drug-naive, rats in place conditioning paradigms. This
      second dopaminergic opiate reward mechanism mediates morphine's alleviation of
      the withdrawal distress associated with abstinence in opiate-dependent animals.
      Furthermore, neuroleptic-induced blockade of food-related motivational effects in
      food-deprived, but not in food-sated (non-food-deprived), animals suggests that
      the neural substrates of motivational events do not dissociate along the line
      between different rewarding stimuli but along the line between deprivation and
      nondeprivation.

PMID- 1359899
TI  - c-erbB-2/neu in colorectal carcinoma: a potential prognostic value?

PMID- 1359901
TI  - Inhibition of specific pathways of myeloid cell differentiation by an activated
      Hox-2.4 homeobox gene.
AB  - Abnormal expression of homeobox genes is one of the abnormalities associated with
      the development of murine and human leukemia. Myeloid leukemic cells that can be
      induced to differentiate to mature cells by interleukin 6 were stably transfected
      with an activated Hox-2.4 homeobox gene. Expression of the Hox-2.4 gene in the
      transfected clones inhibited specific pathways of the myeloid differentiation
      program induced by interleukin 6. The expression of some genes associated with
      differentiation was almost completely blocked, and the expression of other genes
      was either partially inhibited or not affected. The results support the
      hypothesis that abnormal expression of Hox-2.4 may contribute to the development
      of leukemia by interfering with the differentiation program.

PMID- 1359902
TI  - Melanoma and Biology of the Neural Crest. 1992 Keystone Symposium. Taos, New
      Mexico, February 1-8, 1992.

PMID- 1359903
TI  - Use of T-cell growth factors (interleukins 2, 4, 7, 10, and 12) in the evaluation
      of T-cell reactivity to melanoma.
AB  - Melanoma represents the single best example of a human tumor that has been shown
      to elicit specific T-cell reactivity. The responsiveness of some patients with
      metastatic melanoma to treatment with the prototypic T-cell growth factor (TCGF),
      interleukin-2 (IL-2), indicates that T cells play a role in antitumor immunity.
      Interleukin-4 (IL-4), another TCGF that has been administered clinically to
      humans, was not associated with tumor response in our trials conducted at the
      Surgery Branch of the National Cancer Institute. Combination trials of IL-2 with
      IL-4 have shown no increase in responsiveness of melanoma or other tumors when
      compared to IL-2 alone. However, enhanced expansion of tumor-infiltrating
      lymphocytes (TILs) in vitro has been observed with combinations of low-dose IL-2
      and IL-4. We have begun a study evaluating the trafficking of such expanded
      lymphocytes following their adoptive transfer in association with systemic
      administration of IL-2 and IL-4. We have established several TIL cultures from
      fresh tumor samples, maintained them in long-term culture, and marked them with
      the neomycin phosphotransferase gene using the LNL6 retroviral vector. Such TILs
      appear to demonstrate no notable alterations in phenotype or cytolytic activity
      when compared to their nontransduced counterparts. In addition to IL-2 and IL-4,
      there are a variety of other novel TCGFs that are now available for evaluation in
      preclinical and clinical trials. IL-7 induces proliferation and lymphokine
      activated killer (LAK) cell activity from human peripheral blood mononuclear
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359900
TI  - The differentiation pathway of HL60 cells is a model system for studying the
      specific regulation of some myeloid genes.
AB  - During granulopoiesis, certain myeloid genes encoding products of azurophilic
      granules are specifically down-regulated. The myeloid specific enzyme
      myeloperoxidase belongs to this group of genes. It is responsible for the
      production of hypochlorous acid, a potent microbicidal agent which is involved in
      host defense. During induced differentiation of promyelocytic leukemic HL60 cells
      to granulocyte- or monocyte-like cells, myeloperoxidase RNA is depressed. We
      studied this depression process in more detail by limiting the exposure to the
      inducer phorbol 12-myristate 13-acetate to 24 h. During this time period, no
      significant decrease in cell number and cell viability could be observed.
      Analysis of these in vitro differentiated HL60 cells on the protein and RNA
      levels showed that they can be used under defined conditions as a cell system to
      study the specific depression of myeloid genes. Under the described conditions,
      both the transcriptional rate of the myeloperoxidase gene as well as the
      stability of its transcript was reduced.

PMID- 1359904
TI  - Changes in neurotransmitter levels associated with the deficiency of some
      essential amino acids in the diet.
AB  - The contents of dopamine (DA) and serotonin (5-HT) and their metabolites were
      measured in rat substantia nigra and corpus striatum following dietary changes,
      including restriction of protein content (low-protein diet; LPD) and the contents
      of several large neutral amino acids (isoleucine, leucine, methionine,
      phenylalanine, tryptophan and valine) for 25 d. The LPD produced an increase in
      the concentration of tyrosine (TYR) in the two regions of the brain studied. This
      effect was also observed with all amino acid deficiencies studied except for
      valine in the substantia nigra, tryptophan in the striatum and phenylalanine in
      both regions. Likewise, the concentration of 5-hydroxyindoleacetic acid (5-HIAA),
      the main metabolite of 5-HT, increased in the substantia nigra but not in the
      striatum after LPD, as well as with all the amino acid deficiencies studied, with
      the exception of tryptophan deficiency. In this case there was a dramatic effect
      on all components of the serotoninergic system, with decreases in the
      concentration of tryptophan (TRP; precursor), 5-HT and 5-HIAA. This behaviour
      clearly shows an interrelationship between precursor (TRP) availability and 5-HT
      synthesis and metabolism. With valine deficiency, dopaminergic and serotoninergic
      systems demonstrated opposite effects in the substantia nigra and the corpus
      striatum, and the behaviour of the two monoamines was also opposite within each
      structure. The significance of these changes is discussed.

PMID- 1359905
TI  - Identification of aspartic acid 514 through glutamic acid 542 as a glycoprotein
      Ib-IX complex receptor recognition sequence in von Willebrand factor. Mechanism
      of modulation of von Willebrand factor by ristocetin and botrocetin.
AB  - As the first step in hemostasis, the binding of von Willebrand factor (vWF) to
      the platelet membrane glycoprotein (GP) Ib-IX complex is essential for platelet
      adhesion at high-shear blood flow. This interaction in vivo requires the prior
      binding of vWF to the subendothelial matrix, a process which exposes a normally
      cryptic binding site on vWF for the GP Ib-IX complex. This process can be
      mimicked in vitro by modulators such as ristocetin or the snake venom protein
      botrocetin or by desialation of vWF. We have previously localized the GP Ib
      binding site on vWF to a monomeric dispase fragment which extends from Leu
      480/Val-481 to Gly-718 in the primary sequence of mature vWF [Andrews, R. K.,
      Gorman, J. J., Booth, W. J., Corino, G. L., Castaldi, P. A., & Berndt, M. C.
      (1989) Biochemistry 28, 8326-8336]. This fragment also contains a distinct
      binding site for botrocetin. Analysis of synthetic peptides corresponding to
      hydrophilic stretches of sequence within this fragment indicated that the
      sequence Asp-514-Glu-542 represents a major adhesive sequence involved in
      receptor recognition. This peptide inhibited both the ristocetin- and botrocetin
      mediated binding of vWF to either platelets or purified GP Ib-IX complex (IC50
      approximately 50-200 microM) as well as the asialo-vWF- and bovine vWF-dependent
      agglutination of platelets. Both the N- and C-terminal halves of the peptide were
      inhibitory but less so than the intact peptide. This peptide also inhibited
      botrocetin binding to vWF, suggesting that botrocetin modulates vWF-GP Ib
      interaction by binding in close proximity to the vWF adhesion sequence.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1359906
TI  - Thrombin receptor activating peptides: importance of the N-terminal serine and
      its ionization state as judged by pH dependence, nuclear magnetic resonance
      spectroscopy, and cleavage by aminopeptidase M.
AB  - Peptides derived from the recently identified thrombin receptor were tested for
      their ability to induce platelet aggregation in platelet-rich plasma. The 14
      amino acid peptide identified as the new N-terminus after thrombin cleavage (T
      14) and an 11 amino acid peptide (T-11) lacking the 3 C-terminal amino acids of T
      14 were studied. Both induced platelet aggregation at micromolar concentrations,
      with T-11 about twice as potent as T-14. Induction of platelet aggregation by
      these two peptides showed an unusual pH dependence, being more potent at pH 7.2
      than at pH 8.1; thrombin-induced aggregation showed a reverse pH dependence.
      Proton NMR studies of T-11 demonstrated that the chemical shift of the C-alpha
      proton of the N-terminal serine had a pH dependence that mirrored the aggregation
      potency. Acetylating the N-terminus of T-11 resulted in loss of aggregating
      activity, and this peptide did not show the pH-dependence change in chemical
      shift. The T-14 and T-11 peptides lost aggregating activity when incubated in
      plasma due to cleavage of the N-terminal serine by an enzyme identified as
      aminopeptidase M based on its pattern of inhibition and the ability of purified
      aminopeptidase M (EC3.4.11.2) to cleave the T-11 peptide. Endothelial cell
      aminopeptidase M was also able to cleave T-11. Inhibiting aminopeptidase M with
      amastatin enhanced aggregation induced by T-11 but not thrombin. These studies
      suggest that ionization of the N-terminus of the T-11 and T-14 peptides may be
      important in initiating platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359907
TI  - An active-site mutation (Gly633-->Arg) of dipeptidyl peptidase IV causes its
      retention and rapid degradation in the endoplasmic reticulum.
AB  - Dipeptidyl peptidase IV (DPPIV), a serine protease expressed on the cell surface,
      is deficient in a Fischer rat substrain. Northern blot analysis showed no
      difference in the size and amount of DPPIV mRNA between normal (344/NC) and
      deficient (344/CRJ) rats. Cloning and sequencing of DPPIV cDNAs revealed a G to A
      transition at nucleotide 1897 in the cDNA sequence of 344/CRJ, which leads to
      substitution of Gly633-->Arg in the active-site sequence Gly629-Trp-Ser-Tyr
      Gly633 determined for the wild-type DPPIV [Ogata, S., Misumi, Y., Takami, N.,
      Oda, K., & Ikehara, Y. (1992) Biochemistry 31, 2582-2587]. Pulse-chase
      experiments with hepatocytes showed that the wild-type DPPIV was initially
      synthesized as a 103-kDa form with high-mannose-type oligosaccharides, which was
      processed to a mature form of 109 kDa with the complex type during intracellular
      transport. In contrast, the mutant DPPIV, although being synthesized as the 103
      kDa form, was rapidly degraded without being processed to the mature form. Site
      directed mutagenesis of the wild-type and mutant cDNAs and their
      transfection/expression in COS-1 cells confirmed that the single substitution of
      Gly633-->Arg is sufficient to cause the rapid intracellular degradation of DPPIV.
      Immunoelectron-microscopic observations showed that the mutant DPPIV was
      detectable only in the endoplasmic reticulum (ER), in contrast to the
      distribution of the wild-type DPPIV in the Golgi complex and on the cell
      surface.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359909
TI  - [Effects of tranquilizing agents on bioelectrical activity of the rat brain].
AB  - The action of diazepam, meprobamate, trioxazine and mexidol on bioelectrical
      activity of sensorimotor cortex and dorsal hippocamp of the left and right
      hemisphere of the brain in conscious rat in free behavior has been studied. All
      the drugs produced a decline in the frequency of the dominant peak of EEG power
      spectra. Diazepam and meprobamate increased beta-activity. It is concluded that
      the decreased frequency may be due to an anxiolytic effect of the tranquilizers,
      whereas high beta-activity is related to muscle relaxant effect of some drugs.

PMID- 1359908
TI  - Synthesis and beta-adrenergic antagonist activity of novel (3-oxazolinyl-1,4
      dihydropyridyl) propanolamines.
AB  - A novel class of 1-(1-[4-phenyl(n-butyl or methyl)-3-(4,4-dimethyloxazolin-2-yl)
      1,4- dihydropyridyl])-3-tert-butyl(or isopropyl)amino-2-propanols (7-12) were
      synthesized for evaluation as beta-adrenergic antagonists. Replacement of the
      naphthyloxy moiety of propranolol by a 1-[1-(4-n-butyl)-3-(4,4-dimethyloxazolin-2
      yl)-1,4-dihydropyrid yl] group resulted in a significant decrease in cardiac beta
      1-adrenergic antagonist activity which indicates that this group is not a
      suitable isostere for an aryloxy moiety. 1-(1-[4-n-Butyl-3-(4,4-dimethyloxazolin
      2-yl)-1,4-dihydropyridy l])-3- isopropylamino-2-propanol (10) showed a modest
      beta 2-adrenergic antagonist selectivity for trachea (beta 2/beta 1 = 3:1).

PMID- 1359910
TI  - [Transferase contents in lymph and blood in fever reaction].
AB  - The aim of the present investigation was the study of the content of alanine,
      asparagine-transaminases, gamma-glutamyl transferase and their isoenzymes, as
      well as leucine aminotransferase in the lymph of thoracic duct, hepatic and
      intestinal lymph and peripheral blood in dynamics of fever reaction of various
      duration in the experiments on rabbits. Irrespective of its duration, the fever
      was followed by a significant activation of the enzymes in the body fluids.
      However, in many-day fever reaction, a rise of enzymes level in the lymph was
      more prolonged than that in the blood. The above studies make it possible to
      assume that the released enzymes in fever reaction are primarily resorbed by
      lymphatic capillaries and their activity indices in the blood serum are largely
      evidenced by the transport function of the lymphatic system.

PMID- 1359912
TI  - [Study of hematopoietic stem cell pool maintenance in successive transplantations
      using a quantitative method of assessment].
AB  - The ability of transplantable hemopoietic stem cells (HSC) to maintain their pool
      was studied using successive bone marrow transplantations with quantitative
      evaluation of hemopoiesis restoring units (HRU) in each transfer. The number of
      injected HRU increased (3.6-48.6--fold) upon each transfer; however, the normal
      level could not be attained. The ability fo HRU for further multiplication was
      exhausted after five transfers. HRU lost totipotentiality after four transfers.
      The data obtained support the concertion of Kay (1965) that HSC department is a
      pool of heterogeneous cells, and the property of "stemness" is inversely related
      to the number of divisions of ancestral cells. Transplantation, being a
      proliferative stress for the dormant HSCs, thus lowers the stem potential of the
      whole pool. The experimental data suggest that while dividing stem cell does not
      have a choice to self-renew or to differentiate into maturing cells, but it
      really differentiates into HSCs of lower rank.

PMID- 1359911
TI  - [Selective analyzers of dopamine D2 receptors modulate serotonin metabolism in
      the striatum and nucleus accumbens of the rat brain during blockade of
      dopaminergic impulse flow].
AB  - Effects of D2 dopamine receptor selective agonists: quinpirole (0.1, 0.3 and 1
      mg/kg, i. p.), pergolide (0.3 mg/kg, i. p.), lisuride (0.1 mg/kg, i. p.) and
      antagonist raclopride (1.2 mg/kg, i. p.) on the metabolism and synthesis of DA
      and serotonin in the rat brain striatum and nucleus accumbens after GBL treatment
      were studied. GBL as well as dopamine D2 receptor selective drugs were shown not
      only to change neurochemical parameters of dopaminergic brain systems, but also
      to modulate serotonin metabolism without affecting its biosynthesis.

PMID- 1359913
TI  - 15th Annual San Antonio Breast Cancer Symposium. December 7-10, 1992. Abstracts.

PMID- 1359914
TI  - Gallstone lithotripsy: in vitro comparison of fragmentation with a tunable-dye
      laser and an ultrasonic wire.
AB  - Large bile duct stones require fragmentation prior to extraction through the
      papilla or through a percutaneous tract. This can be attempted with dissolution
      therapy, crushing baskets, or lithotripsy. Lithotripsy can be accomplished safely
      and effectively with tunable-dye laser energy delivered through a flexible, 1-F
      optical fiber under endoscopic or fluoroscopic guidance, but laser technology is
      very costly. A prototype, flexible ball-tipped wire coupled to an ultrasonic
      generator via a piezoelectric crystal has been developed for sonolysis of
      atheroma and thrombus in humans. The purpose of this experiment was to compare
      human gallstone fragmentation in vitro with a tunable-dye laser and this
      prototype wire to see if the less expensive ultrasound device might provide an
      alternative to costly laser technology. Gallstones from 17 patients were
      subjected to lithotripsy in a water bath with each device until completely
      fragmented or 60 seconds had elapsed. Neither device effectively fragmented
      cholesterol stones under these conditions. The ultrasonic wire completely
      fragmented 57% of bilirubinate stones in 60 seconds. The tunable-dye laser
      completely fragmented 100% of bilirubinate stones in less than 35 seconds (P =
      .04). Tunable-dye laser lithotripsy appears superior to the ultrasonic device for
      percutaneous treatment of bile duct stones.

PMID- 1359915
TI  - Opiate action in the pulmonary circulation.
AB  - To gain insight into the mechanisms underlying the association between acute
      pulmonary edema and narcotic abuse, the direct action of morphine was examined in
      isolated, perfused left lower lobe (LLL) preparations in dogs and cats. Morphine
      sulphate injected (0.6 mg/kg) into the pulmonary artery of the LLL increased the
      pulmonary vascular resistance (PVR) by about 100% in both species. The increase
      in PVR was primarily due to constriction of the veins, as determined with the
      arterial and venous occlusion technique. The increase in PVR with morphine
      injection was unaffected by alpha-adrenergic antagonists, but was reversed by
      chlorpheniramine, a histamine H1-receptor antagonist. Pretreatment, but not post
      treatment with the opiate antagonist, naloxone, blocked the effect of morphine on
      PVR. Thus, the rapid administration of morphine produces pulmonary
      venoconstriction via histamine release from the lung, and the latter may account
      for the well-documented association between acute pulmonary edema and narcotic
      abuse.

PMID- 1359916
TI  - Nurses and AIDS care.
AB  - The VIIIth International Conference on AIDS held in Amsterdam, July 1992, covered
      many issues pertinent to nurses; however, the lack of nursing participation was
      evident. This article examines the issues of concern to nurses in AIDS care that
      were highlighted at the meeting.

PMID- 1359918
TI  - Selective involvement of kappa opioid and phencyclidine receptors in the
      analgesic and motor effects of dynorphin-A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro.
AB  - Dynorphin A-(1-13)-Tyr-Leu-Phe-Asn-Gly-Pro (Dyn Ia; 1-8 nmol) injected
      intracerebroventricularly in the mouse produces two independent behavioral
      effects: (1) a norbinaltorphimine (kappa opioid antagonist)-reversible analgesia
      in the acetic acid-induced writhing test and (2) motor dysfunction characterized
      by wild running, pop-corn jumping, hindlimb jerking and barrel rolling and
      antagonized by the irreversible phencyclidine (PCP) and sigma (sigma) receptor
      antagonist, metaphit and the non-competitive N-methyl-D-aspartate (NMDA) receptor
      antagonists, dextromethorphan and ketamine. The specific involvement of the PCP
      receptor in the motor effects of Dyn Ia is supported by the direct competitive
      interaction of the peptide with the binding of [3H]MK-801 (Ki: 0.63 microM) and
      [3H]TCP (Ki: 4.6 microM) to mouse brain membrane preparations.

PMID- 1359917
TI  - Isolation of the Arabidopsis ABI3 gene by positional cloning.
AB  - Arabidopsis abi3 mutants are altered in various aspects of seed development and
      germination that reflect a decreased responsiveness to the hormone abscisic acid.
      The ABI3 gene has been isolated by positional cloning. A detailed restriction
      fragment length polymorphism (RFLP) map of the abi3 region was constructed. An
      RFLP marker closely linked to the abi3 locus was identified, and by analyzing an
      overlapping set of cosmid clones containing this marker, the abi3 locus was
      localized within a 35-kb region. An 11-kb subfragment was then shown to
      complement the mutant phenotype in transgenic plants, thereby further delimiting
      the position of the locus. A candidate ABI3 gene was identified within this
      fragment as being expressed in developing fruits. The primary structure of the
      encoded protein was deduced from sequence analysis of a corresponding cDNA clone.
      In the most severe abi3-4 allele, the size of this predicted protein was reduced
      by 40% due to the presence of a point mutation that introduced a premature stop
      codon. The predicted ABI3 protein displays discrete regions of high similarity to
      the maize viviparous-1 protein.

PMID- 1359919
TI  - Intrathecal administration of non-NMDA receptor agonists increases arterial
      pressure and heart rate in the rat.
AB  - We have found that spinal NMDA receptors are involved in control of sympathetic
      output in pathways to the heart and vessels. The present study was done to
      determine whether spinal non-NMDA excitatory amino acid receptors participate in
      cardiovascular regulation. Experiments were done on urethane-anesthetized Sprague
      Dawley rats, giving the non-NMDA receptor agonists, quisqualate and kainate, and
      the antagonist, kynurenate, intrathecally at the spinal T9 level. Both
      quisqualate (30 nmol; n = 7; to activate AMPA receptors) and kainate (2 nmol; n =
      6; to activate K receptors) increased arterial pressure and heart rate. The
      responses were characterized by a rapid onset, achieving, in most cases, greater
      than 80% of the maximum response within 1-4 min, and a persistence throughout the
      remaining 20-24 min of the experiment. I.v. injection of hexamethonium (10 mg/kg)
      prevented the effects of intrathecal administration of quisqualate (n = 5) but
      not of kainate (n = 7). To determine whether the hexamethonium-resistant effects
      of kainate were due to a peripheral action, kainate was given i.v. (n = 6); it
      was found to be without effect on arterial pressure or heart rate. The increases
      in arterial pressure and heart rate produced by intrathecal administration of
      quisqualate (30 nmol; n = 6), kainate (2 nmol; n = 6), glutamate (1 mumol; n = 6)
      and NMDA (2 nmol; n = 6) but not carbachol (27.4 nmol; n = 6) were prevented by
      similar preadministration of kynurenate (125 nmol). Intrathecal administration of
      kynurenate (125 nmol; n = 6; 500 nmol; n = 7) decreased arterial pressure and/or
      heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359920
TI  - Inhibition of alpha 2/alpha 3 sodium pump isoforms potentiates glutamate
      neurotoxicity.
AB  - Excessive stimulation of neurons by glutamic acid initiates a destructive cascade
      of ion fluxes, cellular swelling, and death. Homeostatic mechanisms which rectify
      these disturbances depend largely upon transmembrane ion gradients maintained by
      Na+,K(+)-ATPase (NaP). We proposed that the neurotoxicity of glutamate is
      enhanced when the NaP capacity is exceeded, and therefore, that the degree of
      neuronal death varies inversely with endogenous NaP activity. To test this
      concept, we directly reduced NaP activity in cultured rat telencephalic cells
      using either the specific inhibitor ouabain, or dcAMP, and assessed whether these
      treatments increased glutamate-induced neuronal death. Since rodent NaP catalytic
      subunits possess both low (alpha 1) and high (alpha 2/alpha 3) affinity for
      ouabain, we were able to inhibit selectively the alpha 2 (principally glial) and
      alpha 3 (neuronal) catalytic subunits without affecting the alpha 1 isoform.
      Brief exposures (5-60 min) to high ouabain concentrations (1-10 mM), which blocks
      the activity of all three catalytic subunits, killed differentiated neurons but
      spared glia. In contrast, differential inhibition of the alpha 2/alpha 3 isoforms
      (by 1 microM ouabain) was not of itself toxic, but produced a supersensitivity to
      glutamate. [3H]Ouabain binding studies confirmed that the glutamate neurotoxicity
      observed varied inversely with the degree of NaP inhibition. Further, this
      relationship was not absolutely dependent upon ouabain, since reductions in alpha
      2/alpha 3 pump activity induced by dcAMP also amplified glutamate toxicity. We
      conclude that inhibition of neuronal NaP with high affinity for ouabain is not
      lethal to unstimulated cells, but markedly increases susceptibility to glutamate
      excitotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359921
TI  - Excitatory neurotransmitters in the lateral habenula and pedunculopontine nucleus
      of rat modulate limbic seizures induced by pilocarpine.
AB  - The involvement of the excitatory neurotransmitter system in the lateral habenula
      and pedunculopontine nucleus in the initiation and propagation of limbic seizures
      induced by pilocarpine has been investigated in the rat. Limbic seizures occur in
      animals following bilateral microinjection into the lateral habenula of N-methyl
      D-aspartate (NMDA) (5 and 12.5 nmol) or kainate (100 and 200 pmol), 15 min prior
      to a subconvulsant dose of pilocarpine (150 mg/kg, i.p.). In the absence of
      pilocarpine NMDA (5 and 12.5 nmol) or kainate (100 and 200 pmol), injected
      focally into the lateral habenula or pedunculopontine nucleus, produced sniffing,
      grooming and tremor but no electrographic or behavioural seizures. Limbic
      seizures also occur after a subconvulsant dose of pilocarpine when it is preceded
      by injection of NMDA (5 and 12.5 nmol) or kainate (50, 100 and 200 pmol) into the
      pedunculopontine nucleus. Behavioural and electrographic signs of limbic seizures
      following pilocarpine (380 mg/kg, i.p.) were attenuated or completely antagonized
      by focal injection into the lateral habenula of the NMDA antagonist, 2-amino-7
      phosphonoheptanoate (AP7) (10 and 50 pmol) or kainate antagonist, gamma-D
      glutamylaminomethylsulphonate (GAMS) (20 nmol). In addition, AP7 (0.05, 0.1 and
      1.0 nmol) or GAMS (40 nmol) injected into the pedunculopontine nucleus suppressed
      limbic seizures induced by i.p. administration of pilocarpine (380 mg/kg). The
      relative efficacy of NMDA and non-NMDA receptor antagonists revealed that the
      selective NMDA antagonist, AP7, was more potent in its anticonvulsant activity in
      comparison to GAMS, a non-NMDA receptor antagonist.

PMID- 1359922
TI  - Actions of somatostatin on GABA-ergic synaptic transmission in the CA1 area of
      the hippocampus.
AB  - Somatostatin and gamma-aminobutyric acid (GABA) are co-localized in some neurons
      in the CA1 area of the hippocampus. Since it is possible that the peptide and the
      amino acid are co-released, the interactions between the actions of somatostatin
      and GABA-ergic inhibitory post-synaptic potentials (IPSPs) in the CA1 pyramidal
      neurons of guinea pig hippocampal slices have been investigated. Somatostatin (2
      microM) induced a hyperpolarization of the CA1 neurons associated with a
      reduction in the input resistance of the cells. These effects were not blocked by
      picrotoxinin (20 microM) or phaclofen (1 mM). Chelation of intracellular Ca2+
      (Ca2+i) with BAPTA or the inhibition of protein kinase C (PKC) with sphingosine
      (30 microM) had no significant effects on the hyperpolarizing actions of
      somatostatin. The peptide suppressed the GABAA receptor-mediated fast IPSPs and
      the GABAB receptor-mediated slow IPSPs, but had no significant effect on the
      excitatory post-synaptic potentials (EPSPs). Somatostatin-induced depression of
      the IPSPs was not due to the hyperpolarization of the neurons. Baclofen (20
      microM) suppressed the EPSP, as well as the fast and the slow IPSPs. The
      hyperpolarization of the CA1 neurons caused by somatostatin was greatly reduced
      in the presence of baclofen, an effect that was not due to the hyperpolarization
      of the cell by baclofen. The presence of QX-314 in the CA1 neurons, which
      suppressed the Na+ spikes and the slow IPSPs, prevented the hyperpolarization of
      the neurons by somatostatin and baclofen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359923
TI  - Phosphorylation and activation of tyrosine hydroxylase in PC18 cells: a cell line
      derived from rat pheochromocytoma PC12 cells.
AB  - Treatment of rat pheochromocytoma PC18 cells (a variant subclone of PC12 cells)
      with forskolin produced increased activity and phosphorylation of tyrosine
      hydroxylase. In contrast, treatment of the PC18 cells with 56 mM K+, A23187,
      phorbol-12-myristate-13-acetate (PMA) or phorbol-12,13-dibutyrate (PDB) did not
      affect the activity and only slightly increased the phosphorylation of tyrosine
      hydroxylase. None of the treatments except forskolin increased cyclic AMP levels
      in PC18 cells. Furthermore, 45Ca2+ uptake into PC18 cells was not affected by 56
      mM K+, PDB or forskolin; however, A23187 increased 45Ca2+ uptake 4-fold over
      basal uptake. Nevertheless, no activation and little increase in phosphorylation
      of tyrosine hydroxylase was observed in PC18 cells treated with A23187. When
      tyrosine hydroxylase levels in PC18 cells were elevated by treatment with
      dexamethasone, activation of tyrosine hydroxylase by 56 mM K+, PDB or A23187 was
      still not observed. Both purified Ca2+/calmodulin-dependent protein kinase and
      cyclic AMP-dependent protein kinase catalyzed the phosphorylation of tyrosine
      hydroxylase purified from PC18 cells in vitro. Furthermore, crude cell extracts
      from PC12 cells and PC18 cells possessed Ca2+/calmodulin-dependent protein kinase
      activity that catalyzed the phosphorylation of purified tyrosine hydroxylase.
      These results suggest that tyrosine hydroxylase activity in PC18 cells is
      regulated by a cyclic AMP-dependent mechanism. However, due to a number of
      abnormalities the Ca(2+)-dependent mechanisms do not result in the activation of
      tyrosine hydroxylase and only slightly increase the phosphorylation of the enzyme
      in PC18 cells.

PMID- 1359924
TI  - Role of catecholamines in the modafinil and amphetamine induced wakefulness, a
      comparative pharmacological study in the cat.
AB  - Seventeen adult cats were chronically implanted with electrodes for polygraphic
      recordings in order to assess the role of catecholamines in the arousal effects
      of oral administrations of modafinil, a presumed noradrenergic agonist, and
      amphetamine, a well-known catecholamine-releasing agent. Whereas both modafinil
      (1, 2.5 and 5 mg/kg) and amphetamine (0.25, 0.5 and 1 mg/kg) caused a significant
      and dose-dependent increase in wakefulness and brain temperature, amphetamine,
      but not modafinil, elicited marked signs of behavioral excitation. Pretreatments
      with alpha-methyl-DL-p-tyrosine methyl ester (50 mg/kg, i.p.), an inhibitor of
      catecholamine synthesis, almost completely prevented the effects of amphetamine
      (0.25 and 1 mg/kg), but only slightly reduced the duration of the waking effect
      of modafinil (2.5 and 5 mg/kg). Pretreatments with phentolamine (10 mg/kg, i.p.),
      prazosin (1.5 mg/kg, per os) and propranolol (5 mg/kg, i.p.), an alpha-, alpha 1-
      and beta-receptor antagonist, respectively, attenuated significantly the arousal
      effect of modafinil (1 mg/kg, the same as below) but not of amphetamine (0.25
      mg/kg, the same as below). Intraperitoneal injections of haloperidol (0.5 mg/kg),
      a dopamine-receptor antagonist, blocked significantly the arousal of amphetamine
      but not of modafinil. The effects of both modafinil and amphetamine were enhanced
      by a pretreatment with yohimbine (1 mg/kg, i.p.), an alpha 2-receptor antagonist.
      These results suggest that the arousal effect of modafinil does not depend on the
      availability of the endogenous catecholamines but results from an enhancement of
      alpha 1- and beta-receptor activity and that the waking and behavioral effects of
      amphetamine may be mainly due to an increase in dopamine release.

PMID- 1359925
TI  - Theta burst stimulation is optimal for induction of LTP at both apical and basal
      dendritic synapses on hippocampal CA1 neurons.
AB  - The efficacy of stimulation patterns consisting of brief high frequency bursts
      repeated at various intervals to induce long-term potentiation (LTP) at synapses
      on apical and basal dendrites of CA1 hippocampal neurons was tested in vitro.
      Both apical and basal dendritic synapses exhibited maximal LTP after bursts
      repeated at 5-10 Hz, i.e. close to the frequency of the endogenous hippocampal
      theta rhythm. As at apical dendritic synapses, LTP at basal dendritic synapses
      was blocked by an antagonist of NMDA receptors. Basal dendritic LTP was
      significantly greater in magnitude than apical dendritic LTP, although the reason
      for this is unknown.

PMID- 1359928
TI  - [Summary of the Third Symposium on Functional Study and Surgical Operation of the
      Spleen].

PMID- 1359926
TI  - Muscarinic nature of cholinergic receptors in the cerebellar flocculus involved
      in the enhancement of the rabbit's optokinetic response.
AB  - Intrafloccular micro-injection of the aselective cholinergic agonist carbachol
      enhances the optokinetic reflex (OKR)17. Histochemical and physiological studies
      have identified cholinergic receptors of the muscarinic as well as nicotinic type
      in the cerebellar cortex, and both have been implicated in cholinergic
      transmission. The present study was undertaken to elucidate the receptor type
      involved in the control of OKR. For that purpose, effects of injections of the
      nicotinic N1 agonist DMPP on the OKR and vestibulo-ocular reflex (VOR) were
      compared with injections of the muscarinic agonist betanechol and the aselective
      cholinergic agonist carbachol. Injection of betanechol mimicked the enhancement
      of the OKR by carbachol, while DMPP had no effect. We conclude that muscarinic
      receptors are involved in the positive modulatory action of the cholinergic
      system in the cerebellar flocculus.

PMID- 1359927
TI  - Virus-neuron interaction: an experimental model.

PMID- 1359929
TI  - [Clinical application of reverse island flap with first metatarsal dorsal
      vessels].

PMID- 1359930
TI  - Cardioprotective effects of carvedilol, a novel beta adrenoceptor antagonist with
      vasodilating properties, in anaesthetised minipigs: comparison with propranolol.
AB  - OBJECTIVE: The aim was to evaluate in a minipig model of acute myocardial
      infarction the cardioprotection provided by the beta adrenoceptor blocking and
      vasodilating activities present in carvedilol; comparison was made to the pure
      beta adrenoceptor antagonist, propranolol. METHODS: Experiments were performed in
      25 Yucatan minipigs (9-12 kg), randomly assigned to receive vehicle (n = 7),
      carvedilol 0.3 mg.kg-1 (n = 6), carvedilol 1 mg.kg-1 (n = 6), or propranolol 1
      mg.kg-1 (n = 6). Myocardial infarction was produced by occlusion of the left
      anterior descending coronary artery for 45 min followed by 4 h of reperfusion.
      Vehicle, carvedilol (0.3 and 1 mg.kg-1) or propranolol (1 mg.kg-1) were given
      intravenously 15 min before the coronary artery occlusion. At the end of the
      reperfusion period, infarct size was determined using Evans blue dye and
      triphenyltetrazolium chloride staining. Infarct volumes were visualised using
      computer assisted three dimensional image analysis of the stained myocardial
      tissue sections. Myeloperoxidase activity was measured in tissue samples removed
      from normal, infarcted, and at risk areas. RESULTS: Carvedilol (1 mg.kg-1)
      reduced infarct size by over 90% without producing pronounced changes in systemic
      haemodynamic variables. The ability of carvedilol to reduce infarct size was
      clearly dose dependent. Thus infarct size, which represented 27.5(SEM 2.3)% of
      the area at risk in the vehicle treated group, was only 13.1(4.0)% (p < 0.05) and
      2.4(1.5)% (p < 0.01) in pigs treated with carvedilol at 0.3 and 1 mg.kg-1,
      respectively. In animals treated with propranolol (1 mg.kg-1), infarct size
      represented 10.9(2.4)% of the area at risk (p < 0.05). The 60% and 91% reductions
      in infarct size produced by propranolol (1 mg.kg-1) and carvedilol (1 mg.kg-1),
      respectively, were clearly evident upon three dimensional image analysis. The
      reduction in infarct size was significantly greater for carvedilol (1 mg.kg-1)
      compared to propranolol (1 mg.kg-1) at equivalent beta adrenoceptor blocking
      doses. Pretreatment with propranolol did not reduce the increases in
      myeloperoxidase activity observed in the area at risk or in the infarcted area.
      In contrast, carvedilol produced a dose dependent reduction in myeloperoxidase
      activity in these areas. CONCLUSIONS: Carvedilol limits myocardial necrosis
      resulting from coronary artery occlusion and reperfusion in a more pronounced
      manner than the pure beta adrenoceptor antagonist, propranolol. The
      cardioprotective effect of carvedilol, which reduced infarct size by 91%, may
      result from the combined effects of beta adrenoceptor blockade and
      vasodilatation, and possibly also from inhibition of intracellular calcium
      overload in cardiac cells resulting from antagonism of myocardial alpha 1
      adrenoceptors and/or calcium channel blockade. The cardioprotection provided by
      carvedilol may ultimately be of benefit in hypertensive patients who are at risk
      for acute myocardial infarction.

PMID- 1359931
TI  - Studies on antiulcer drugs. VI. 4-Furyl-2-guanidinothiazoles and related
      compounds as potent histamine H2-receptor antagonists.
AB  - A series of 4-furyl-2-guanidinothiazole derivatives and related compounds were
      synthesized and evaluated for histamine H2-receptor antagonist and gastric acid
      antisecretory activities. Among them, compounds I-17, I-48 and I-49 showed high
      activities in these tests. In addition, compound I-17 possessed potent inhibitory
      activities on each of the gastric ulcers induced by stress, ethanol and HCl
      aspirin. On the other hand, compound I-48 demonstrated antimicrobial activity
      against Helicobacter Pylori and the potency was far stronger than that of
      clinically used H2-antagonists. Some structure-activity relationships are
      discussed.

PMID- 1359932
TI  - Keratinized epithelial transport of beta-blocking agents. I. Relationship between
      physicochemical properties of drugs and the flux across rat skin and hamster
      cheek pouch.
AB  - The maximum fluxes (Jmax) of beta-blockers through keratinized membranes were
      determined in vitro and compared with their physiochemical parameters such as
      lipophilicity (log k'0) and melting point (mp). Rat abdominal skin and hamster
      cheek pouch mucosa were used as the model membranes. Propranolol, metoprolol,
      timolol, pindolol, nadolol and agenolol were used as beta-blockers with a variety
      of physicochemical characters. Linear relations of Jmax with either log k'0 or mp
      were observed both in intact rat skin and in intact hamster cheek pouch,
      suggesting that the lipophilicity and thermodynamic activity of a drug in the
      crystal state primarily affect the drug's permeation through these membranes.
      However, the slope, dJmax/d(log k'0), for cheek pouch mucosa was greater than
      that for rat skin, corresponding to the lack of appendigeal shunt pathways in
      cheek pouch. Penetration studies using the delipidized membranes and the isolated
      stratum corneum sheet of hamster cheek pouch mucosa clarified that the primary
      rate-limiting barrier function might exist in the lipid layer of the stratum
      corneum. Jmax values for the tape-stripped and delipidized skins correlated with
      both the solubilities of drugs in the vehicle and with the mp, suggesting the
      polar porous characteristics of both model membranes. However, a theoretical
      approach confirmed that the contribution of an intracellular or aqueous pore
      route in the intact membrane to the permeation of drugs with positive lipophilic
      indexes is negligible.

PMID- 1359933
TI  - Proceedings of the Interdisciplinary Symposium on Gene, Nutrition and Health,
      1991. Gene-Environment Interactions in Cardiovascular Diseases. Japan, 1 October
      1991.

PMID- 1359934
TI  - Renin gene restriction fragment length polymorphisms in a Japanese family with a
      high incidence of essential hypertension.
AB  - 1. Human renin gene restriction fragment length polymorphisms (RFLP) were
      compared in a Japanese family which has a high incidence of essential
      hypertension. 2. RFLP of human renin gene were observed in three restriction
      enzymes, Mbo I, Bgl I and Hind III; 1.4 kb and 1.0 kb [Mbo I], 5.0 kb and 9.0 kb
      [Bgl I] and 9.0 and 6.2 kb [Hind III]. 3. Plasma renin activity was not
      associated with blood pressure. 4. Renin gene RFLP were not cosegregated with
      essential hypertension in this Japanese family.

PMID- 1359935
TI  - The roles of intracellular buffers and bone mineral in the regulation of acid
      base balance in mammals.
AB  - 1. Regulation of intracellular and extracellular pH may conflict in their
      requirements for movement of acid or base. 2. Cells make a positive or a negative
      contribution to 'tissue buffering' of extracellular fluid (ECF), depending on
      their internal buffer value, on the tightness of their internal pH control by
      membrane mechanisms, and on the nature of the acid-base disturbance. 3. A role is
      suggested for electrogenic Na-HCO3 co-transport in some of the ion shifts that
      occur in acid-base disturbances. 4. The time course of 'tissue buffering' in
      nephrectomized mammals in hypercapnia is variable, and it is far from clear in
      intact, unanaesthetized mammals. 5. Buffering of ECF by Ca salts of bone mineral
      in acidosis can only be substantial if accompanied by Ca excretion; the release
      of HCO3 with Na and K is more significant. 6. The relative importance of cells
      and of bone mineral in the buffering of ECF is unclear.

PMID- 1359936
TI  - A new source of biologically active compounds--earthworm tissue (Eisenia foetida,
      Lumbricus rubelus).
AB  - 1. Earthworms possess immunological recognition and memory as well as high
      regenerative abilities. Coelomic fluid was used as a source of biologically
      active compounds. 2. A biologically active glycolipoprotein extract from a whole
      earthworm tissue homogenate was isolated and named G-90. 3. G-90 forms
      precipitation arcs in gel with different animal and human sera. 4. It alters
      murine cell growth rate in vitro in serum in a dose-dependent manner and slows
      murine tumor growth in vivo. 5. G-90 does not contain mutagens or carcinogens.

PMID- 1359937
TI  - Basic biochemical data on blood from antarctic Weddell seals (Leptonychotes
      weddelli): ions, lipids, enzymes, serum proteins and thyroid hormones.
AB  - 1. Standard laboratory values of blood samples taken from Weddell seals in
      Antarctica were determined. 2. Numerous blood parameters are similar to those
      observed in man. 3. Comparatively high cholesterol levels but normal triglyceride
      levels were observed when compared with humans. 4. In comparison to laboratory
      findings in humans, T4 levels were decreased although T3 levels were normal. 5.
      The levels of alkaline phosphatase are considerably higher than those in humans.
      6. The data obtained indicate different lipid and thyroid hormone metabolism in
      Weddell seals when compared with humans.

PMID- 1359938
TI  - Correlations between serum corticosterone concentration and reproductive
      conditions in the white-footed mouse (Peromyscus leucopus noveboracensis).
AB  - 1. Adrenal size and activity in reproductively inhibited young born into
      laboratory populations of the white-footed mouse were examined. Measurements were
      made of body weight, reproductive organ weight and adrenal weight. Serum
      corticosterone was measured by radioimmunoassay. 2. Data from reproductively
      inhibited animals were compared with corresponding values from reproductively
      capable animals of the same sex. The mean paired testis and seminal vesicle, or
      paired ovary and uterus, weights, were significantly reduced in reproductively
      inhibited animals of both sexes. The paired adrenal weights were not different in
      any comparison. 3. Reproductively inhibited males selected from laboratory
      populations had a mean corticosterone concentration that was significantly higher
      than the corresponding value for reproductively capable males. Females showed no
      significant difference in mean serum corticosterone concentrations. 4. The
      results are discussed in relation to earlier studies in two species of Peromyscus
      and the apparent paradox of elevated serum corticosterone in the absence of
      adrenal hypertrophy.

PMID- 1359939
TI  - A possible relationship between KCl symport and basolateral K(+)-conductance in
      Necturus gallbladder epithelial cells.
AB  - 1. Apical membrane potential (Va), transepithelial potential (VT), fractional
      apical voltage ratio (FVa = delta Va/delta VT), tissue resistance (RT), and
      intracellular Cl- (aiCl) and K+ (aiK) activities were measured in isolated
      gallbladders maintained between oxygenated bicarbonate-free physiological media
      (23 degrees C, pH 7.2 or 8.2) in a divided chamber. The basolateral membrane
      potential (Vb) was calculated from the measured values of Va and VT. 2. Cl-
      removal from the serosal medium (which should accelerate coupled basolateral KCl
      exit) significantly depolarized Vb, decreased aiCl, decreased FVa, increased RT,
      and attenuated the depolarization of Vb (delta Vb) induced by high K+ added to
      the serosal side. These changes are consistent with a decrease in the K(+)
      conductance of the basolateral membrane (gbK). 3. Addition of furosemide (an
      inhibitor of KCl cotransport) to the serosal medium induced significant increases
      in Vb, FVa, and high K(+)-induced delta Vb, indicating an increase in gbK. 4. In
      the presence of serosal furosemide, Cl- removal from the serosal medium did not
      significantly alter Vb, aiCl or delta Vb from their corresponding values when
      serosal Cl- was present. 5. Serosal furosemide had no significant effect on aiK
      and aiCl measured with double-barreled ion-selective microelectrodes. 6. These
      results suggest the possibility of a reciprocal relationship between gbK and the
      rate of basolateral KCl cotransport. This may contribute to the maintenance of
      aiK in gallbladder epithelial cells.

PMID- 1359940
TI  - Comparative hematology: studies on guinea-pigs (Cavia porcellus).
AB  - 1. Guinea-pig blood clots rapidly and the clots retract in glass tubes. The
      prothrombin time is long and the activated partial thromboplastin time short
      compared to human. The Russel viper venom time is similar to human. 2. Factors
      VII and X assay at levels far below and factors V, VIII and XII assay far above
      human levels. Other coagulation factors (fibrinogen, II, IX, XI, Fletcher and
      Fitzgerald) assay within or close to the human range. 3. The thromboplastin
      generation test results for guinea-pigs and humans are similar. 4. Platelets are
      numerous and small. They aggregate with ADP, arachidonic acid and pig plasma,
      variably with ristocetin and poorly with bovine collagen or thrombin. On electron
      microscopy, platelets appear small with many dark granules (dense bodies). There
      is an open canicular system. Glycogen particles are sparse. Microtubules are
      occasionally seen, mitochondria are rare and alpha-granules are not readily
      distinguished from dark granules. 5. Ristocetin cofactor is very low, assaying at
      < 16% of human (< 0.16 U/ml). 6. Leukocyte counts are variable (6300-17,000 per
      microliters) and differential counts show neutrophils slightly lower and
      lymphocytes slightly higher than average human counts. 7. Guinea-pig erythrocyte
      parameters fall within human ranges. 8. Protein electrophoresis shows total
      protein and albumin to be slightly lower than human. 9. Antithrombin III, Protein
      C and alpha 2-antiplasmin assay within the human range and plasminogen at very
      low levels. 10. Bleeding times are consistently about 4 min.

PMID- 1359941
TI  - Auditory-evoked brainstem responses in the hibernating woodchuck Marmota monax.
AB  - 1. This study measured the changes in the auditory-evoked brainstem responses in
      the woodchuck (Marmota monax) during hibernation and arousal. 2. The auditory
      brainstem response of the euthermic woodchuck consisted of four waves occurring
      in a 10 msec time window after stimulation. 3. In the hibernating woodchuck,
      waves I and II could be traced down to the lowest body temperatures. 4. As
      temperatures increased all the components of the ABR emerged. The latencies of
      all the waves showed systematic decrease with temperature increments, the effect
      being cumulative across the time window. 5. These findings reflect activity in
      the VIIIth cranial nerve and the cochlear nuclei during hibernation and
      restoration of the functional integrity of the brainstem auditory pathway during
      arousal.

PMID- 1359942
TI  - The effects of established diabetes on the growth of the fetal liver and skin in
      the rat.
AB  - 1. The effects of uncontrolled maternal diabetes on the growth of the whole rat
      fetus and its liver and skin were studied over the last 4 days of gestation. 2.
      Smaller fetuses, with growth-retarded livers and skins, were consistently found
      between 18 and 21 days in the diabetic pregnancies. 3. The smaller diabetic
      livers and skins (i.e. combined epidermis and dermis) possessed lower protein,
      RNA and DNA contents, compared with the same fetal tissues from normal
      pregnancies. 4. The growth retardation of the livers in diabetic fetuses was
      attributed to fewer normally sized hepatic cells. 5. Whilst hepatic rates of
      protein synthesis (measured in vivo) remained largely unchanged, these were
      actually increased in the skin, compared with normal control tissues. 6. These
      findings point to an elevated rate of protein degradation in both diabetic
      tissues as the most likely cause of their retarded growth.

PMID- 1359943
TI  - Effects of recombinant human growth hormone on anorexic Nile crocodiles
      (Crocodylus niloticus).
AB  - 1. Eleven-month-old Nile crocodiles with poor appetite and retarded growth were
      injected with 0.325 micrograms/g recombinant human growth hormone (hGH) twice a
      week for 4 weeks. 2. The treated animals had a mean intake per meal of 29.8 g/kg,
      while the controls ate only 2.8 g/kg. 3. The treated group gained 8.1% of their
      initial body weight, while the controls lost 6.3%. 4. During 4 weeks of treatment
      the body and head length increased by 3.93 and 1.29%, respectively, while no
      linear growth took place in the controls. 5. The treated group had higher
      contents of skeletal muscle protein and liver glycogen than the control group. 6.
      In conclusion, recombinant hGH induces appetite and growth in anorexic
      crocodiles.

PMID- 1359944
TI  - Fibre digestion and digesta retention from different physical forms of the feed
      in the rabbit.
AB  - 1. Digestibility of fibre was higher in guinea-pigs than in rabbits, however, the
      digestibility of hemicellulose fraction containing agar was similar in both
      animals. 2. The digestibility of fibre of a fine particle diet was higher than
      that of a large particle diet in the rabbit permitted coprophagy, whereas it was
      lower in the rabbit prevented from coprophagy. 3. The fine particle diet tended
      to cause shorter retention time of digesta in the rabbit prevented from
      coprophagy. 4. These suggest that the digestibility of fine components relates to
      their physical properties which affect the retention time of digesta in the
      rabbit.

PMID- 1359945
TI  - Effects of pantethine on lipogenesis and CO2 production in the isolated
      hepatocytes of the chick (Gallus domesticus).
AB  - 1. Isolated hepatocytes from chicks were used to study the effects of pantethine
      supplementation to incubation medium on in vitro lipogenesis, CO2 production and
      beta-oxidation of fatty acid. 2. In vitro lipogenesis, determined by the
      incorporation of 1-[14C]acetate into total lipid and various lipid fractions, as
      depressed in concordance with the increase of pantethine concentration in the
      medium. 3. Incubation of isolated hepatocytes with pantethine resulted in a
      significant decrease (P < 0.01) in the activities of acetyl-CoA carboxylase and
      fatty acid synthetase. 4. The results suggest that in vitro fatty acid synthesis
      from 1-[14C]acetate was depressed and CO2 production was elevated in hepatocytes
      of chicks through pantethine addition to the medium at a low level.

PMID- 1359946
TI  - Size distribution of adipocytes and variation in adipocyte number in lines of
      mice selected for high or low body fat.
AB  - 1. Adipocyte size and number were measured in epididymal fat pads from lines of
      mice selected for high or low body fat. 2. Epididymal fat pad weight at 10 weeks
      of age was 4-fold greater in the high fat than the low fat mice, accompanied by a
      7-fold greater adipocyte volume but there was no difference in adipocyte number.
      Smaller differences in fatness and cell volume were observed at younger ages. 3.
      The high fat mice showed one or two populations of cells up to 5 weeks of age and
      at 7 weeks 3 days and 10 weeks showed two or more populations. In contrast, the
      low fat animals at all ages showed either one or two populations. 4. These
      findings imply that greater lipogenesis and cell filling, not cell proliferation,
      is the primary mechanism of increased fatness in these selected lines of mice.

PMID- 1359947
TI  - Effects of exercise and food restriction in pregnant and newborn rats. Pre
      pregnancy maximum oxygen consumption.
AB  - 1. In the present study, the effects of exercise and food restriction in pregnant
      and newborn rats were investigated. 2. The following groups were formed: adequate
      food supply, with and without exercise (AE and AN) and 30% food restriction, with
      and without exercise (RE and RN). 3. Exercise was performed throughout the
      pregnancy on a treadmill at a speed of 18 m/min for 30 min/day, which represented
      84% of maximum VO2. 4. The results show that food restriction affected body
      weight gain while exercise only affected the RE group (P < 0.05). 5. Body
      temperature was increased by exercise. The initial temperature was lower in group
      RE. 6. No differences were obtained in average offspring number but reabsorption,
      preterm and natimortality were observed in group RE. 7. Newborn body weight was
      lowered by food restriction rather than by exercise. 8. Newborn brain and heart
      weights were not affected but lung and liver weights were significantly affected
      by the nutritional factor (P < 0.05).

PMID- 1359948
TI  - Presynaptic modulation of sensory afferents in the invertebrate and vertebrate
      nervous system.
AB  - 1. Ultrastructural examination of the central terminals of sensory afferent
      neurons in both invertebrates and vertebrates demonstrates that the synapses that
      form the substrate for presynaptic inhibition and facilitation are almost
      universally present. 2. Presynaptic modulation of afferent input acts in many
      ways which tailor the inflow of sensory information to the behaviour of the
      animal, effectively providing a means of turning this on and off, or of combining
      information of the same or different modalities to refine responsiveness or
      clarify ambiguity. 3. Presynaptic modulation may act in several different roles
      on the same afferent. 4. A comparison of the mechanisms of presynaptic inhibition
      in different animals demonstrates the likelihood of a variety of common
      mechanisms, several of which may act simultaneously on the same terminal. These
      include changes in the conductance of the afferent membrane to Cl-, K+ and Ca2+
      ions, in addition to less well understood mechanisms that directly affect
      transmitter release. 5. A single transmitter can produce several effects on a
      terminal through the same or different receptors. 6. Ultrastructural studies of
      afferent terminals reveal that only a proportion of boutons on a given afferent
      may receive presynaptic input and that this may depend on the region of the
      nervous system in which these are found or on the identity of the postsynaptic
      neurons contacted. 7. The synaptic relationships of afferent terminals can be
      complex. In invertebrates different types of presynaptic neuron may interact
      synaptically, as may postsynaptic dendrites in vertebrates. 8. Axons presynaptic
      to afferent terminals in vertebrates frequently synapse also with dendrites
      postsynaptic to the afferents. 9. In both invertebrates and vertebrates
      reciprocal interactions between afferents and postsynaptic neurons are seen. 10.
      Ultrastructural immunocytochemistry reveals the likely dominance of GABA as an
      agent of presynaptic inhibition but also demonstrates the possible presence of
      other transmitters some of whose roles are less completely understood.

PMID- 1359949
TI  - Periodicity and diversity in ant mating flights.
AB  - 1. Flight hours and seasons are alike within species, but differ among species
      and among genera. 2. Laboratory studies indicate internal circadian control of
      the phase relation to the light-dark cycle, with field evidence for modification
      by temperature (or other environmental variables). 3. In at least two species
      there is abrupt loss of obvious rhythm after mating, suggesting some special
      function before loss, e.g. to facilitate cross-breeding within species or
      reproductive isolation between species.

PMID- 1359950
TI  - Aldosterone increases the amiloride-sensitivity of the rat gustatory neural
      response to NaCl.
AB  - 1. The percentage inhibition of the chorda tympani neural response to NaCl by
      topical application of amiloride to the tongue was significantly larger in rats
      pretreated with aldosterone than in control animals. 2. Adrenalectomized rats
      pretreated with aldosterone had significantly larger amiloride-induced
      inhibitions to a NaCl stimulus than did adrenalectomized control animals. 3.
      These data suggest that aldosterone may increase the number of active amiloride
      sensitive sodium channels in the apical membrane of taste cells, as is known to
      occur in sodium transporting tissues of amphibians and mammals. They additionally
      represent a previously unnoticed hormonal influence over the gustatory system.

PMID- 1359951
TI  - Monoamines and their metabolites in the amphibian (Ambystoma tigrinum) brain:
      quantitative changes during metamorphosis and captivity.
AB  - 1. Monoamine neurotransmitters (epinephrine, norepinephrine, dopamine, serotonin
      and some of their metabolites (DOPEG, MHPG, DOPAC, 5-HIAA) were measured by HPLC
      in extracts from telencephalon (TEL) and diencephalon-midbrain (DM) before,
      during at the end of metamorphosis. 2. During metamorphosis MHPG increased and 5
      HIAA decreased in TEL and DM while DOPEG decreased only in DM. 3. Monoamine
      levels were greater in the TEL and a larger increase in MHPG occurred there. 4.
      Captivity without metamorphosis also caused a significant depression of 5-HIAA in
      TEL and depression of DOPEG, MHPG and DOPAC in DM.

PMID- 1359952
TI  - Neutral amino acid transport in an androgen-dependent epithelium.
AB  - 1. Transport of neutral amino acids by the isolated seminal vesicle epithelium of
      normal and gonadectomized guinea pigs has been investigated by measurement of the
      uptake of 2-amino[1-14C]-isobutyric acid and 2-methylamino[1-14C]isobutyric acid.
      2. The Vmax for Na-dependent and -independent transport of both amino acids was
      reduced by gonadectomy but the general transport characteristics appeared to be
      unchanged by this treatment. 3. The most likely explanation of the decreased
      transport is the loss of transporter molecules associated with the tissue
      regression that follows rapidly on gonadectomy.

PMID- 1359953
TI  - Sex-specific androgen binding in spotted hyaena (Crocuta crocuta) plasma.
AB  - 1. A charcoal adsorption assay demonstrated a large variance in androgen binding
      ability in female spotted hyaenas. 2. A positive correlation between plasma
      androgen binding ability and ovarian steroid concentrations was demonstrated in
      adult females. 3. The strong plasma binding affinity for testosterone and
      dihydrotestosterone (DHT) (nM) together with the lack of cortisol and weaker
      oestradiol-17 beta binding suggests that a specific androgen binding substance,
      possibly a protein, is present in adult females of this species. 4. The lack of
      high affinity binding in male spotted hyaenas is unusual and deserves further
      investigation. 5. Some androgen binding in all, including males and immature
      animals suggests that albumin may bind some plasma androgens in this species.

PMID- 1359954
TI  - The metabolic output of avian (Sturnus vulgaris, Calidris alpina) adipose tissue
      liver and skeletal muscle: implications for BMR/body mass relationships.
AB  - 1. The oxygen uptake rate of avian adipose tissue, liver and skeletal muscle
      slices were measured. 2. The energy consumption of fat was less than one tenth
      that of liver and muscle. 3. Thus, interspecific allometric equations for the
      prediction of basal metabolic rate from body mass will not be accurate throughout
      the avian annual cycle unless changes in body composition are taken into account.

PMID- 1359955
TI  - Core and periphery concentrations of short-chain fatty acids in luminal contents
      of the rat colon.
AB  - 1. The regional concentration of short-chain fatty acids was higher in the core
      than in the periphery of the round slices of contents. 2. Marked circadian and
      segmental fluctuations existed in their concentrations.

PMID- 1359956
TI  - Adaptive changes in total pyruvate dehydrogenase activity in lipogenic tissues of
      rats fed high-sucrose or high-fat diets.
AB  - 1. Pyruvate dehydrogenase complex (PDC) activity was measured in several tissues
      of rats fed for 7 or 15 days on control, or high-sucrose or high-fat diets. 2.
      Total activity in adipose tissue increased in the three groups 3-4 fold as
      compared with chow-fed animals in the first week. Total activity was 60% lower in
      rats fed the diet containing 22% corn oil for 2 weeks. 3. Hepatic total and PDCa
      activities were 50-80% higher in rats fed the sucrose diet for 7 or 15 days and
      decreased 30-40% in those fed on the high-fat diet for 2 weeks.

PMID- 1359957
TI  - Development of hepatic microsomal activity of 3-hydroxy-3-methylglutaryl-coenzyme
      A reductase and cholesterol 7 alpha-hydroxylase in the young chick.
AB  - 1. The 3-hydroxy-3-methylglutaryl-CoA reductase activity increased from 1 to 4
      weeks of age, but decreased from 4 to 8 weeks of age. 2. Cholesterol 7 alpha
      hydroxylase activity increased from 1 to 4 weeks, decreased from 4 to 6 weeks,
      and increased again from 6 to 8 weeks of age. 3. Serum total and free cholesterol
      concentrations decreased from 1 to 6 weeks of age, but increased from 6 to 8
      weeks of age.

PMID- 1359958
TI  - Sonographic measurement of diaphragmatic motion after coronary artery bypass
      surgery.
AB  - Forty-eight patients were prospectively evaluated following coronary artery
      bypass grafting (CABG) in order to determine values for diaphragmatic mobility by
      sonography, to compare diaphragmatic motion to chest x-ray findings, to relate
      diaphragmatic motion to pulmonary function tests, and to determine whether use of
      the left internal mammary artery (LIMA), aortic cross-clamp time, or other
      clinical variables were predictive of diaphragmatic dysfunction. Mean left
      diaphragmatic motion was 2.8 +/- 1.1 cm (range, 1.0 to 5.7 cm), mean right
      diaphragmatic motion was 3.9 +/- 1.1 cm (range, 1.8 to 6.4 cm), and ratio of left
      to right motion was 0.74 +/- 0.27 (range, 0.19 to 1.4). Forty-one patients had
      normally positioned diaphragms on the chest x-ray film; four of these had poor
      mobility by ultrasonography (< 1.6 cm). Of the seven elevated left hemidiaphragms
      on chest x-ray films, three had an excursion of 1.6 cm or more by
      ultrasonography. The mean FVC for all patients was 59 +/- 13 percent of
      predicted. There was no relationship between diaphragmatic mobility and FVC or
      negative inspiratory pressure. The diaphragmatic motion in 36 patients having
      LIMA grafting was similar to those without (2.7 +/- 1.2 cm [n = 36] vs 2.8 +/-
      0.8 cm [n = 12], respectively). Aortic cross-clamp time and respiratory symptoms
      also did not correlate with diaphragmatic mobility. Sonography can be used in the
      evaluation of diaphragmatic motion after CABG and may be more accurate in
      detecting a poorly mobile diaphragm than is the chest x-ray film.

PMID- 1359959
TI  - The islet amyloid polypeptide gene and non-insulin-dependent diabetes mellitus in
      south Indians.
AB  - Islet amyloid polypeptide (IAPP), otherwise called amylin, is the monomeric
      component of islet amyloid. Deposition of this amyloid is a characteristic
      feature of non-insulin-dependent diabetes mellitus in humans and may play a role
      in the pathogenesis of the disease. As such, abnormalities in the structure or
      expression of the IAPP gene might contribute to the inheritance of this
      condition. The IAPP gene was studied in a well-characterised population of 62
      unrelated Dravidian subjects with non-insulin-dependent diabetes mellitus and 56
      normal Dravidian controls, using a restriction fragment length polymorphism
      generated by PvuII digestion. Genotype and allele frequencies did not differ
      between diabetic subjects and controls. Taken together with recent findings in
      Europid and other racial groups, an abnormality of the IAPP gene is highly
      unlikely to represent a major gene for the development of non-insulin-dependent
      diabetes mellitus.

PMID- 1359960
TI  - Serotonin-induced decrease in hypothalamic tyrosine hydroxylase activity and
      corresponding increase in prolactin release are abolished at midpregnancy and by
      transplants of rat choriocarcinoma cells.
AB  - We investigated the effect of central serotonin (5-hydroxytryptamine, 5-HT)
      administration on hypothalamic tuberoinfundibular dopamine neurons and related
      changes in neuronal activity to circulating PRL levels in two physiological
      models: 1) pregnant rats expressing (day 8) or not expressing (days 11 and 16)
      PRL surges, and 2) ovariectomized rats transplanted with rat choriocarcinoma
      cells, which secrete functional placental lactogen-I. Over a 4-min period between
      0900 and 1400 h, rats were administered either vehicle or 5-HT (20 micrograms/6
      microliters) through lateral ventricular cannulae. Plasma PRL levels were
      determined by RIA. NSD 1015 (25 mg/kg intraarterial), a dihydroxyphenylalanine
      (DOPA) decarboxylase inhibitor, was injected 20 min after initiation of
      ventricular infusion. Ten min later, the stalk-median eminence (SME) was
      dissected. The rate of DOPA accumulation, determined by measuring DOPA levels in
      the SME by HPLC, was used as an index of tyrosine hydroxylase catalytic activity,
      indicating tubero infundibular dopamine neuronal activity. In day-8 pregnant rats
      5-HT reduced DOPA accumulation to 57% of vehicle-injected controls and increased
      circulating PRL levels 13-fold. In contrast, on days 11 and 16 of pregnancy 5-HT
      did not alter DOPA accumulation in the SME or plasma PRL levels. In nonpregnant
      rats ovariectomized for 24 h, 5-HT decreased DOPA accumulation in the SME to 43%
      of vehicle-infused controls and increased PRL levels approximately 26-fold.
      However, in nonpregnant rats with rat choriocarcinoma cells, 5-HT produced no
      changes in either DOPA accumulation in the SME or in circulating PRL levels. The
      inability of 5-HT to reduce tyrosine hydroxylase activity after mid-pregnancy may
      account for the lack of a PRL response. Placental lactogens secreted at
      midpregnancy, particularly placental lactogen-1, may induce this loss of 5-HT
      effect.

PMID- 1359961
TI  - Differential effects of neuroexcitatory amino acids on corticotropin-releasing
      hormone-41 and vasopressin release from rat hypothalamic explants.
AB  - We have investigated the direct effects of different neuroexcitatory amino acids
      (EAA) on the secretion of CRH-41 and arginine vasopressin (AVP) from the rat
      hypothalamus maintained in vitro. CRH-41 and AVP released in the medium were
      assayed by RIA before and after incubation with N-methyl-D-aspartate (NMDA), N
      methyl-D,L-aspartic acid, kainate (KA), and quisqualate in the concentration
      range 1 nM to 1 mM in either the absence or the presence of 1 mM Mg2+ in the
      medium. In the case of NMDA, the effect of the addition of glycine (1 and 10
      microM) to the incubation medium was also studied. Finally, we investigated
      whether different periods of exposure (up to 100 min) of hypothalamic explants to
      NMDA and KA would affect CRH-41 release. While no EAA was able to induce CRH-41
      release under any of the above conditions, 20-min incubations with NMDA in the
      dose range of 1 nM to 1 mM in the absence of added Mg2+ significantly stimulated
      AVP release in a dose-related fashion; the maximum effect occurred at a
      concentration of 1 mM [ratio of stimulated collection/basal collection: NMDA,
      1.51 +/- 0.10, controls, 0.86 +/- 0.05 (mean +/- SEM); P < 0.001]. KA also showed
      a dose-related stimulatory effect in the dose range of 1 nM to 1 mM, with maximal
      AVP stimulation at 10 microM (KA, 1.91 +/- 0.28; controls, 0.90 +/- 0.03; P <
      0.01). The effects of both NMDA and KA on AVP were completely reversed by the
      competitive antagonists D,L-2-amino-5-phosphonovaleric acid and 6-cyano-7
      nitroquinoxaline-2,3 dione, respectively, at doses 10 times higher than those of
      the agonists. N-Methyl-D,L-aspartic acid stimulated AVP secretion only at a dose
      of 10 mM (P < 0.01), whereas quisqualate was ineffective at any concentration.
      The addition of 1 mM Mg2+ to the medium blocked the effect of NMDA, while
      attenuating AVP stimulation induced by KA. The stimulatory effect of KA on AVP
      was significantly reduced by D-L-2-amino-5-phosphonovaleric acid (P < 0.05),
      suggesting that KA may also act through NMDA receptors. Moreover, the presence of
      glycine in the incubation medium did not result in any effect of NMDA on CRH-41
      secretion, nor did it appear to potentiate NMDA-induced AVP release.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1359962
TI  - Inhibitory effects of ethanol on the growth hormone (GH)-releasing hormone-GH
      insulin-like growth factor-I axis in the rat.
AB  - Ethanol administration decreases GH secretion in humans and experimental animals.
      The mechanism of these inhibitory effects was investigated by evaluating the
      spontaneous secretory pattern of GH in chronically cannulated unanesthetized
      rats, plasma insulin-like growth factor-I (IGF-I) concentrations, and
      hypothalamic GH-releasing hormone (GHRH) and somatostatin, and pituitary GH mRNA
      levels. Body weight gain was reduced in ethanol (5%)-liquid diet-fed rats (n = 6)
      for 6 days compared to that in both isocalorically pair-fed controls (n = 6) and
      ad libitum-fed animals (n = 6). Spontaneous GH secretion was markedly decreased
      (by 75-90%) in ethanol-fed rats compared to that in pair-fed and ad libitum-fed
      groups, while pulsatile pattern of GH release was preserved, with secretory
      bursts occurring every 180-220 min in all groups. Mean 6-h plasma GH levels in
      ethanol-, pair-, and ad libitum-fed animals were: 18.8 +/- 4.5, 113.3 +/- 14.9,
      and 179.6 +/- 30.1 ng/ml, respectively (P < 0.01, ethanol vs. each control).
      Plasma IGF-I concentrations were decreased in the ethanol-fed rats (338 +/- 16
      ng/ml) compared to those in pair-fed (427 +/- 39 ng/ml; P < 0.05) and ad libitum
      fed (769 +/- 25 ng/ml; P < 0.01) rats. Ethanol treatment decreased GHRH mRNA
      levels to 9% of those in ad libitum-fed (P < 0.01) and 20% of those in pair-fed
      (P < 0.05) animals, whereas it did not significantly alter somatostatin or GH
      mRNA levels. The results indicate that the effects of ethanol inhibit GH
      secretion primarily at the hypothalamic level, resulting in impaired GHRH gene
      expression. Since the GHRH-GH-IGF-I axis has an important role in growth
      regulation, the growth retardation seen in experimental models of alcohol abuse
      may be a consequence at least in part of the suppressive effects of ethanol on
      this axis.

PMID- 1359963
TI  - Ontogeny of insulin-induced hypoglycemia stimulation of adrenocorticotropin
      secretion in the rat: role of catecholamines.
AB  - We previously reported that insulin-induced hypoglycemia (IIH) induces a large
      increase in plasma ACTH and corticosterone levels in the developing rat during
      the stress hyporesponsive period and that this effect is mediated, at least
      partially, by arginine vasopressin (AVP), but not corticotropin-releasing factor.
      Nevertheless, ACTH secretion in response to IIH in rats immunoneutralized against
      AVP was still stimulated, suggesting that other regulatory factors participate in
      the stimulation of ACTH secretion during IIH. It has been suggested that, in the
      adult rat, during profound hypoglycemia, epinephrine may act at the pituitary
      level through beta 2-adrenergic receptors to stimulate ACTH secretion. In this
      report, we studied the effect of the blockade of beta-adrenergic receptors on the
      pituitary-adrenal axis response to IIH. Rats (20 or 8 day old) were pretreated
      with saline or 2.5 mg/kg propranolol (a beta-adrenergic receptors antagonist) and
      subsequently injected with 3 IU/kg insulin. In 20-day-old rats, insulin injection
      induced a large increase of plasma ACTH concentrations that were unaffected by
      propranolol pretreatment. In 8-day-old rats, the IIH-induced increase of plasma
      ACTH levels was significantly reduced by propranolol pretreatment. Pretreatment
      of 8-day-old rats with 5 mg/kg CGP 20712A (a selective beta 1-adrenergic receptor
      antagonist) did not change the plasma ACTH response to insulin injection, while
      pretreatment with 2.5 mg/kg ICI 118551 (a selective beta 2-adrenergic receptor
      antagonist) resulted in a significant decrease of the IIH-induced stimulation of
      ACTH secretion. We next studied the effect of the blockade of circulating AVP
      and/or beta-adrenergic receptors on the pituitary response to IIH. Pretreatment
      of 8-day-old rats with antiserum anti-AVP or propranolol was followed by a
      significant reduction of IIH-induced increase of plasma ACTH concentrations. No
      additive effect was found after pretreatment with both antiserum anti-AVP and
      propranolol, suggesting that the stimulatory effect of catecholamines during IIH
      in 8-day-old rats is mediated through a modulation of hypothalamic AVP secretion.

PMID- 1359965
TI  - Biosynthesis and metabolism of dipeptidylpeptidase IV in primary cultured rat
      hepatocytes and Morris hepatoma 7777 cells.
AB  - N-Glycosylation, biosynthesis and degradation of dipeptidylpeptidase IV (EC
      3.4.14.5) (DPP IV) were comparatively studied in primary cultured rat hepatocytes
      and Morris hepatoma 7777 cells (MH 7777 cells). DPP IV had a molecular mass of
      105 kDa in rat hepatocytes and of 103 kDa in MH 7777 cells as assessed by
      SDS/PAGE under reducing conditions. This difference in molecular mass was caused
      by differences in covalently attached N-glycans. DPP IV from hepatoma cells
      contained a higher proportion of N-glycans of the oligomannosidic or hybrid type
      and therefore migrated at a slightly lower molecular mass. In both cell types DPP
      IV was initially synthesized as a 97-kDa precursor which was completely
      susceptible to digestion with endo-beta-N-acetylglucosaminidase H converting the
      molecular mass to 84 kDa. The precursor was processed to the mature forms of DPP
      IV, glycosylated with N-glycans mainly of the complex type with a half-life of 20
      25 min. The transit of newly synthesized DPP IV to the cell surface displayed
      identical or very similar kinetics in both cell types with the major portion of
      DPP IV appearing at the cell surface after 60 min. DPP IV molecules were very
      slowly degraded in hepatocytes as well as in hepatoma cells with half-lives of
      approximately 45 h. Inhibition of oligosaccharide processing with 1
      deoxymannojirimycin led to the formation of DPP IV molecules containing N-glycans
      of the oligomannosidic type. This glycosylation variant was degraded with the
      same half-life as complex-type glycosylated DPP IV. By contrast, inhibition of N
      glycosylation with tunicamycin resulted into rapid degradation of non-N
      glycosylated DPP IV molecules in both cell types. Non-N-glycosylated DPP IV could
      not be detected at the cell surface indicating an intracellular proteolytic
      process soon after biosynthesis.

PMID- 1359964
TI  - Effects of cysteamine administration on somatostatin biosynthesis and levels in
      rat hypothalamus.
AB  - A single injection of cysteamine (CSH; 2-aminoethanethiol; 300 mg/kg, sc) into
      male rats produced a rapid decline in immunoreactive somatostatin (IR-SRIF)
      levels in the hypothalamus (to 20% of preinjection values within 12 h) which
      persisted for several days. The levels of both somatostatin-14 (SRIF-14) and
      somatostatin-28 (SRIF-28) were reduced. In contrast, the levels of somatostatin
      28(1-12) were unaffected. Most (80-90%) of the lost SRIF molecules (both SRIF-14
      and SRIF-28) could be recovered from CSH-injected rats by subjecting hypothalamic
      samples to denaturing, reducing, and reoxidizing conditions. These results
      suggest that CSH does not deplete the hypothalamus of SRIF molecules, but,
      instead, alters their chemical structures, rendering them undetectable using a
      SRIF-14-directed RIA. CSH injection also caused a rapid and complete suppression
      (within 1 h) of [35S]cysteine incorporation into SRIF-14 and SRIF-28. This
      reduction, however, was short-lived; normal incorporation rates returned within
      10 h of drug administration. CSH did not influence [35S] cysteine incorporation
      into acid-precipitable protein or [35S]cysteine specific activity in the
      hypothalamus. In addition, [35S]SRIF molecules were not recovered from
      hypothalami of CSH-treated rats by subjecting samples to denaturing, reducing,
      and then reoxidizing conditions. These findings indicate that CSH injection
      causes a true, but short-lived (1- to 10-h), suppression of hypothalamic SRIF-14
      and SRIF-28 formation. Finally, biosynthesis studies of longer duration revealed
      no prolonged effects of CSH. The drug produced no changes 4, 24, or 72 h
      postinjection in hypothalamic levels of the prepro-SRIF mRNA. Moreover, two
      injections of CSH, separated by 3 days, which continuously suppressed IR-SRIF
      levels for almost 1 week, caused only a transient suppression of [35S]SRIF-14 and
      [35S]SRIF-28 synthesis after each injection. These results indicate that the SRIF
      biosynthetic pathway is not activated by the prolonged CSH-induced depletion of
      IR-SRIF stores.

PMID- 1359966
TI  - The incorporation of divalent metal ions into recombinant human tyrosine
      hydroxylase apoenzymes studied by intrinsic fluorescence and 1H-NMR spectroscopy.
AB  - Three isoforms of human tyrosine hydroxylase were expressed in Escherichia coli
      and purified to homogeneity as the apoenzymes (metal-free). The apoenzymes
      exhibit typical tryptophan fluorescence emission spectra when excited at 250-300
      nm. The emission maximum (342 nm) was not shifted by the addition of metal ions,
      but reconstitution of the apoenzymes with Fe(II) at pH 7-9 reduced the
      fluorescence intensity by about 35%, with an end point at 1.0 iron atom/enzyme
      subunit. The fluorescence intensity of purified bovine adrenal tyrosine
      hydroxylase, containing 0.78 mol tightly bound iron/mol subunit, was reduced by
      only 6% on addition of an excess amount of Fe(II). Other divalent metal ions
      [Zn(II), Co(II), Mn(II), Cu(II) and Ni(II)] also reduced the fluorescence
      intensity of the human enzyme by 12-30% when added in stoichiometric amounts. The
      binding of Co(II) at pH 7.2 was also found to affect its 1H-NMR spectrum and this
      effect was reversed by lowering the pH to 6.1. The quenching of the intrinsic
      fluorescence of the human isoenzymes by Fe(II) was reversed by the addition of
      metal chelators. However, the addition of stoichiometric amounts of
      catecholamines, which are potent feedback inhibitors of tyrosine hydroxylase, to
      the iron-reconstituted enzyme, prevented the release of iron by the metal
      chelators. Fluorescence quenching, nuclear magnetic relaxation measurements and
      EPR spectroscopy all indicate that the reconstitution of an active holoenzyme
      from the isolated apoenzyme, with stoichiometric amounts of Fe(II) at neutral pH,
      occurs without a measurable change in the redox state of the metal. However, on
      addition of dopamine or suprastoichiometric amounts of iron, the enzyme-bound
      iron is oxidized to a high-spin Fe(III) (S = 5/2) form in an environment of
      nearly axial symmetry, thus providing an explanation for the inhibitory action of
      the catecholamines.

PMID- 1359967
TI  - Probing the active site of the reconstituted aspartate/glutamate carrier from
      mitochondria. Structure/function relationship involving one lysine and two
      cysteine residues.
AB  - Treatment of the reconstituted aspartate/glutamate carrier from mitochondria with
      7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (Nbd-Cl) led to complete inactivation of
      carrier function. Inhibition could be attributed to chemical modification of one
      single cysteine in the active site. This residue was specifically protected in
      the presence of aspartate or glutamate, 50% substrate protection being observed
      at half-saturation of the external binding site. The bifunctional reagent 4,4'
      diisothiocyanostilbene-2,2'-disulfonate (DIDS) also modified the same cysteine
      and, in addition, an active-site lysine identified previously [Dierks, T.,
      Stappen, R., Salentin, A. & Kramer, R. (1992) Biochim. Biophys. Acta 1103, 13
      24]. The proximity of the cysteine [Cys(a)] and the lysine residue was confirmed
      by a mutual exclusion of the respective reagents when added consecutively. By
      using a variety of reagents a further cysteine [Cys(b)] and probably a histidine
      residue could be discriminated from Cys(a) and the lysine. The applied reagents
      were classified according to functional and structural criteria. Class A
      reagents, like Nbd-Cl, modified the active-site Cys(a) thereby inhibiting the
      antiport function. Class B reagents, like HgCl2, reacted with both Cys(a) and
      Cys(b) leading to a conversion of the carrier from antiport to uniport function
      [Dierks, T., Salentin, A., Heberger, C. & Kramer, R. (1990) Biochim. Biophys.
      Acta 1028, 268-280]. DIDS at relatively high concentration (60 microM) also acted
      as a uniport inducer. Class C reagents finally, like pyridoxal phosphate or
      diethyl pyrocarbonate, modified the active-site lysine or histidine,
      respectively, and blocked antiport and uniport activity. By testing the
      accessibility of the mentioned residues to the various reagents, when applied in
      different order, topological relationships could be elaborated indicating the
      location of these amino acids with respect to the exofacial active site of the
      carrier protein.

PMID- 1359968
TI  - Afferent lymph veiled cells prime CD4+ T cell responses in vivo.
AB  - The interdigitating cell (IDC) population of the lymph node paracortex is
      believed to be responsible for the induction of CD4+ T cell responses to soluble
      antigens. We have examined the role of afferent lymph veiled cells (ALVC), the
      putative precursors of IDC, in the induction of primary bovine CD4+ T cell
      responses in vivo. ALVC prepared from lymph draining an antigen inoculation site
      stimulated maximal responses in antigen-specific T cell clones as soon as 30 min
      after inoculation. In addition, antigen-pulsed ALVC were shown to induce primary
      antigen-specific T cell responses when administered in vivo. Observed influences
      of fixation and the addition of chloroquine or class II major histocompatibility
      complex-specific monoclonal antibodies on presenting function confirmed that ALVC
      process and present antigens using the endosomal pathway. We conclude that ALVC
      rapidly internalize antigens deposited in the periphery, and process them for
      presentation to naive T cells in the draining lymph node. Their function is,
      therefore, likely to be an important factor in the induction of primary T cell
      responses to soluble antigens in vivo.

PMID- 1359969
TI  - Role of T cell subsets during the recall of immunologic memory to Leishmania
      major.
AB  - The contributions of different T cell subpopulations to the maintenance of
      immunity during secondary Leishmania major infections were analyzed in healed,
      resistant animals by depletion of T cell subsets in vivo. The strong delayed-type
      hypersensitivity mounted in immune genetically resistant mice upon challenge with
      viable promastigotes was mediated by both CD4+ and CD8+ T cells. Each T cell
      subpopulation alone contributes, although to a different extent, to the
      resolution of secondary lesions; both subsets, however, are required for an
      efficient and rapid healing of the secondary lesions and the decrease in the
      parasite burden in infected tissues. The results indicate that in immune,
      genetically resistant CBA mice, the activity of both T cell subsets is required
      for successful resistance to reinfection and an efficient maintenance of
      immunity.

PMID- 1359970
TI  - Regulation of tumor necrosis factor (TNF)-alpha synthesis and TNF receptors
      expression in T lymphocytes through the CD2 activation pathway.
AB  - The involvement of the CD2 (T11) molecule, an alternative activation pathway for
      T lymphocytes, in the regulation of tumor necrosis factor (TNF)-alpha/TNF
      receptor system in human T lymphocytes has been investigated. It has been found
      that both TNF-alpha synthesis and secretion were induced after incubation of
      purified T lymphocytes with the appropriate mitogenic combination of antibodies
      specific for two different epitopes on the CD2 molecule. Moreover, TNF-alpha
      secretion was also observed by activation of T lymphocytes either through CD3 or
      CD69 molecular pathways, or with other stimulating agents such as Ca2+ ionophore
      in combination with phorbol esters. The expression of TNF receptors has been
      studied in both nonactivated and CD2-activated T lymphocytes. Unstimulated T
      cells weakly expressed a functional 75-kDa receptor form, whereas they lacked
      detectable levels of the 55-kDa receptor form. Triggering of T cell activation
      through the CD2 molecule also markedly increased the expression of the p75-kDa
      TNF receptor form, but did not exert any inductive effect on the expression of
      the p55-kDa TNF receptor. In addition, we have found that TNF-alpha enhanced the
      proliferative response triggered by the mixture of anti-CD2 monoclonal
      antibodies. Taken together, these results support a role for the CD2 activation
      pathway in the functional regulation of TNF-alpha/TNF receptor system in T
      lymphocytes, and reinforce the view of CD2 as an alternative pathway for
      regulation of the cytokine network that modulates the function of T lymphocytes.

PMID- 1359971
TI  - Peritoneal sanctuary for human lymphopoiesis in SCID mice injected with human
      peripheral blood lymphocytes from Epstein-Barr virus-negative donors.
AB  - The successful engraftment in SCID mice of intraperitoneally (i.p.) injected
      human lymphocytes (hu-PBL-SCID) and the failure of intravenously injected
      peripheral blood lymphocytes (PBL) directed the present study to investigate the
      early events of donor cell proliferation in the peritoneal cavity. We found focal
      lymphocyte engraftment together with histio-monocytic interleukin (IL)-6+ cell
      phenotypes which must have been transferred with the human cell inoculum, which
      could explain certain immune functions observed in hu-PBL-SCID chimeras.
      Following i.p. injection of 10(8) PBL, human cells suspended in peritoneal fluid
      as well as those adherent to the serosal peritoneum and abdominal organs were
      investigated by immunocytology and immunohistology. Human cells were found to
      form foci consisting predominantly of proliferating human lymphoblastoid CD3+
      cells, which were mostly activated HLA-DR+ CD8+ lymphocytes. Among the lymphoid
      cells larger epithelioid-like cells were found to belong to the monocytic series
      and to stain strongly with anti-HLA-DR and anti-CD11c antibodies. Some of these
      cells were also positive with anti-ICAM and anti-IL-6. Congenic as well as
      allogeneic mouse PBL, injected i.p. into SCID mice, temporarily produced
      analogous foci, which shifted later on to foci similar in appearance to milky
      spots. However, the human cell foci appeared less compact, more closely
      resembling in vitro-culture soft agar colonies. It is possible that cytokines in
      the human histio-monocytic cells of the foci may have a feeder effect on the
      human lymphocytes and be a prerequisite for proliferation of human PBL in SCID
      mice. The observed early HLA-DR activation of human lymphocytes in the peritoneal
      foci could reflect triggering of immune reactions like xenogeneic graft-versus
      host reactions in the peritoneal site, where the human CD11c+ HLA-DR+ histio
      monocytic cells may act as antigen-presenting cells.

PMID- 1359972
TI  - An activated murine B cell lymphoma line (A-20) produces a factor-like activity
      which is functionally related to human natural killer cell stimulatory factor.
AB  - In the present article we show that supernatants derived from lipopolysaccharide
      (LPS) or phorbol 12-myristate 13-acetate (PMA)-stimulated A-20 B cell lymphoma
      are able to induce polyclonal immunoglobulin (Ig) secretion by normal B cells in
      a T-cell-dependent manner. This activity could be blocked by neutralizing
      monoclonal antibodies against interferon-gamma, but not by monoclonal antibodies
      against interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10 and granulocyte macrophage
      colony-stimulating factor (GM-CSF) or even a polyclonal antibody against tumor
      necrosis factor (TNF)-alpha. Furthermore, A-20 supernatants induced the
      production of measurable amounts of interferon-gamma by normal murine spleen
      cells and activates natural killer (NK) cells. Fractionation of factor-rich
      supernatants on a Sephacryl S-200 column revealed that the factor activity is
      located in the fractions corresponding to a molecular mass of 160-150 kDa and 80
      70 kDa. The biological activities found in the A-20 supernatant are very similar
      to the ones described for the recently cloned human IL-12/NK cell stimulatory
      factor. These results suggest the existence of a murine analogous factor for the
      human IL-12 produced by A-20 B cell lymphoma.

PMID- 1359973
TI  - Characterization of the binding of [3H](+)-pentazocine to sigma recognition sites
      in guinea pig brain.
AB  - The selective sigma compound (+)-pentazocine was radiolabeled and its binding
      characteristics in guinea pig brain membranes were investigated. [3H](+)
      Pentazocine bound to a single high-affinity site with a KD of 2.9 nM and a Bmax
      of 1998 fmol/mg protein. Saturation was achieved at a ligand concentration of 15
      nM. Maximal specific binding was observed at 37 degrees C and was greater than
      90% of total binding. Equilibrium was reached by 120 min and dissociation was
      complete by 420 min, with a t1/2 of 121 min. Li+, Ca2+ and Mg2+ inhibited binding
      at high concentrations, and binding was insensitive to adenyl and guanyl
      nucleotides. Stereoselectivity was observed for the inhibition of binding by
      benzomorphans, 3-(3-hydroxyphenyl)-N-propylpiperidine and butaclamol, and the (+)
      enantiomers and alpha diastereomers of pentazocine and cyclazocine were more
      potent than their corresponding (-) enantiomers and beta diastereomers. The rank
      order of potency for the sigma reference agents to displace [3H](+)-pentazocine
      binding was similar to that reported using the [3H]sigma ligands
      dextromethorphan, 1,3-di(2-tolyl)guanidine and (+)-3-(3-hydroxyphenyl)-N
      propylpiperidine. Haloperidol, (+)-pentazocine, (+)-3-(3-hydroxyphenyl)-N
      propylpiperidine and rimcazole were competitive inhibitors of binding to the
      [3H](+)-pentazocine-defined sigma recognition site, suggesting that these
      different structural classes of compounds all bind to a single molecular entity.

PMID- 1359974
TI  - Atypical molecular pharmacology of a new long-acting beta 2-adrenoceptor agonist,
      TA 2005.
AB  - The molecular pharmacology of a new putative long-acting bronchodilator TA 2005
      (8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(p-methoxy-phenyl)- 1
      methylethyl]amino]ethyl]carbostyril hydrochloride) has been compared with that of
      the reference compounds isoprenaline and salbutamol in both methacholine (3 x 10(
      6) M) precontracted guinea pig tracheal smooth muscle relaxation and in bovine
      trapezium muscle binding experiments. TA 2005 appeared very potent compared with
      isoprenaline and salbutamol (pD2 values of 9.29 vs. 7.65 and 7.10 respectively).
      For isoprenaline and salbutamol a shallow displacement curve was observed and
      addition of the non-hydrolysable GTP analogue guanylyl-imidodiphosphate (GppNHp)
      gave a rightward shift (pKd,high and pKd,low values of 7.3 and 6.1 vs. 7.0 and
      5.4 respectively). For TA 2005 a steep displacement curve was found with only one
      binding state even without GppNHp (pKd,high value of 8.2). The long duration of
      action of TA 2005 might be explained by tight binding of this compound to the
      beta 2-adrenoceptor. The extent of tight binding for TA 2005 was extremely large.
      The molecular basis of the tight agonist binding phenomenon for TA 2005 seems to
      be of different origin than for isoprenaline. It is hypothesized that a different
      mechanism of activation of the beta 2-adrenoceptor may be involved for TA 2005.

PMID- 1359975
TI  - Pharmacologic characterization of cloned alpha 1-adrenoceptor subtypes: selective
      antagonists suggest the existence of a fourth subtype.
AB  - In membranes prepared from Cos-7 or HeLa cells expressing one of three individual
      cloned alpha 1-adrenoceptor subtypes, competition with 2-[(beta-(4-hydroxy-3
      [125I]iodophenyl)ethylaminomethyl]-tetralone ([125I]HEAT) by the selective
      compounds [+]-niguldipine, 5-methyl-urapidil, and benoxathian reveals high
      affinity for the cloned alpha 1C-adrenoceptor subtype and low affinity for both
      the cloned alpha 1A-adrenoceptor and alpha 1B-adrenoceptor. Competition with
      [125I]HEAT by spiperone revealed high affinity for the cloned alpha 1C
      adrenoceptor, intermediate affinity for the cloned alpha 1B-adrenoceptor, and low
      affinity for the cloned alpha 1A-adrenoceptor. Combining pharmacological
      properties previously described for alpha 1-adrenoceptor subtypes in rat
      membranes and here described from cloned receptors, these data suggest the
      existence of a fourth distinct alpha 1-adrenoceptor subtype.

PMID- 1359976
TI  - Visualization of dopamine D3-like receptors in human brain with [125I]epidepride.
AB  - In sections of human brain containing the striatum (caudate, nucleus, putamen,
      nucleus accumbens) the competition for binding of [125I]epidepride by compounds
      with differing selectivity for dopamine D2 and D3 receptors was examined.
      Domperidone showed higher affinity for D2-like than D3-like sites whereas 7-OH
      DPAT (7-hydroxy-2-(N,N-di-n-propylamino)tetralin) and quinpirole demonstrated the
      reverse selectivity. The pattern of [125I]epidepride binding in the presence of a
      high concentration of domperidone was negligible in the dorsal striatum but
      indicated islands of dense binding to D3-like receptors in the nucleus accumbens
      and ventral putamen.

PMID- 1359977
TI  - The glutamate- and glycine-induced reduction of [3H]MK-801 binding in the
      presence of Mg2+ is reversed at low pH.
AB  - At normal pH, glutamate and glycine are known to inhibit [3H]MK-801 binding in
      the presence of Mg2+. We found, however, that at pH 5.4 glutamate and glycine
      enhance [3H]MK-801 binding in rat cerebrocortical membranes. Furthermore, H+,
      similarly to Mg2+, inhibited basal [3H]MK-801 binding. These results indicate
      that H+ competes with binding sites for Mg2+ and [3H]MK-801, and may be
      correlated to the depression in neuronal activity observed during acidosis.

PMID- 1359978
TI  - Metipranolol-induced adverse reactions: I. The rechallenge study.
AB  - Previously unreported adverse drug reactions can be difficult to detect and it
      may be even more difficult to establish a cause and effect relationship,
      particularly if the adverse reactions mimic naturally occurring disease. In a
      previous paper we reported 29 patients with granulomatous anterior uveitis,
      blepharoconjunctivitis, periorbital dermatitis, marginal keratitis and elevation
      in intraocular pressure (IOP), suspected to be caused by metipranolol (Glauline).
      With the approval of the District Ethics Committee 7 of those patients were
      rechallenged with metipranolol 0.3% compared to timolol maleate 0.5% in a double
      blind trial. The 7 metipranolol treated eyes developed an adverse reaction within
      14 days. Metipranolol (Glauline) has been conclusively proven to cause
      granulomatous anterior uveitis, blepharoconjunctivitis and elevation in IOP,
      adverse effects never previously reported with any of the ophthalmic topical beta
      blockers. The multidose preparations of metipranolol (Glauline) in all three
      strengths 0.1%, 0.3% and 0.6% and the single dose minim preparation of
      metipranolol 0.6% have now been withdrawn from clinical use in the United
      Kingdom.

PMID- 1359979
TI  - Metipranolol-induced adverse reactions: II. Loss of intraocular pressure control.
AB  - This paper reviews the behaviour of intraocular pressure (IOP) in glaucomatous
      eyes treated with metipranolol with and without drug-induced adverse reactions
      (ADRs). Two hundred and forty seven patients with open angle glaucoma who were
      receiving the three different strengths of metipranolol (0.1%, 0.3%, and 0.6%) in
      our Department and the 7 patients who participated in the metipranolol
      rechallenge trial were included in this study. Out of the 247 patients, there
      were 52 eyes of 29 patients who showed 78 episodes of ADRs associated with
      metipranolol. Forty five of these 78 episodes (57.6%) were associated with loss
      of IOP control. Two of the 7 eyes treated with metipranolol in the rechallenge
      trial showed loss of IOP control, 1 of them without any signs of ocular
      inflammation. We further studied all the glaucomatous eyes controlled with
      metipranolol 0.6% only and 22 eyes were identified with loss of IOP control but
      without recognisable signs or symptoms of ADR. Five other eyes in this group
      later developed metipranolol-induced ADRs. The possible pathophysiological
      mechanisms for the loss of IOP control are discussed and it is suggested that the
      active drug, metipranolol, could be directly implicated.

PMID- 1359980
TI  - Prolactin gene expression in human thymocytes.
AB  - Recent evidence suggests that lymphocytes produce prolactin (PRL). Here, we
      report the cDNA cloning and expression of PRL from normal human thymocytes.
      Sequence analysis showed that the thymocyte cDNA encodes a 23 kDa protein which
      is identical to pituitary PRL. RNA blot analysis showed that the thymocyte PRL
      mRNA is approximately 170 nucleotides larger than the pituitary PRL message. PRL
      message was also detected in several non-pituitary human cell lines including
      Jurkat T, HeLa, and JEG cells. Furthermore, PRL gene expression in JEG cells was
      inhibited by glucocorticoid treatment. Our data support the hypothesis that PRL
      is a T cell-derived cytokine.

PMID- 1359981
TI  - Report of the 7th European Workshop on Molecular and Cellular Endocrinology of
      the Testis.

PMID- 1359982
TI  - Developmental expression of the growth hormone gene in the gilthead sea bream
      Sparus aurata.
AB  - Expression of growth hormone (GH) gene during early stages of larval development
      of the teleost Sparus aurata was determined by Northern blot analysis. Poly(A+)
      RNA was prepared from a pool of larvae collected on different days after
      hatching. When hybridized to Sparus aurata GH cDNA, GH specific mRNA was first
      seen on day 6 post-hatching. In contrast, the levels of beta-actin mRNA, which
      was used to normalize for RNA amounts, were already high on the day of hatching.
      Our results suggest that expression of the GH gene is very low immediately after
      hatching, and increases dramatically within 6 days.

PMID- 1359983
TI  - Characterisation of adult Sertoli cell cultures from cryptorchid rats: inhibin
      secretion in response to follicle-stimulating hormone stimulation.
AB  - Testes from adult (90-120-day-old) rats, which had been made cryptorchid 28 days
      previously, were dispersed by successive treatment with trypsin, collagenase and
      hyaluronidase. The resulting crude cell suspension was fractionated on
      discontinuous Percoll density gradients to yield five distinct cell bands (1-5),
      at the interface between successive layers of Percoll. Crude cells and purified
      fractions were cultured for up to 7 days, and inhibin was subsequently measured
      in the media by radioimmunoassay and in vitro bioassay. Sertoli cells from
      density gradient bands 2 (1.03-1.04 g/ml) and 3 (1.04-1.05 g/ml) showed minimal
      germ cell or peritubular cell contamination, as determined by morphological and
      histochemical techniques. Cells from these bands secreted significantly higher
      levels of immunoactive inhibin/microgram DNA/48 h under both basal and either
      follicle-stimulating hormone (FSH)- (100 ng/ml) or dibutyryl cAMP-stimulated (100
      micrograms/ml) conditions than did cells from the other bands. While there was a
      decline in basal secretion of inhibin with increasing duration of culture, the
      capacity of the purified Sertoli cells (bands 2 and 3) to respond to both FSH and
      dibutyryl cAMP increased over the culture period. The addition of dibutyryl cAMP
      (31.25-500 micrograms/ml) to the purified Sertoli cells also caused a stimulation
      of bioactive inhibin. Immunoactive inhibin production by purified Sertoli cells
      was unaffected by the addition of either rat LH (8 ng/ml) or testosterone (10(-6)
      M). The data describe a method for the isolation of adult Sertoli cells from
      cryptorchid testes, and demonstrate their responsiveness to both FSH and
      dibutyryl cAMP in vitro using the measurement of immunoactive inhibin as a marker
      of Sertoli cell function.

PMID- 1359984
TI  - Stabilization of follicle-stimulating hormone-receptor complexes may involve
      calcium-dependent transglutaminase activation.
AB  - Calcium-dependent transglutaminase (TGase) activity, determined by incorporation
      of [1,4-14C]diaminobutane dihydrochloride (putrescine) into casein, was
      demonstrated in a light membrane fraction prepared from bovine calf testicular
      homogenates. Purification of these membranes by sucrose density gradient
      centrifugation produced a follicle-stimulating hormone (FSH) receptor-enriched
      fraction containing TGase activity which cosolubilized with the FSH receptor and
      could be incorporated with detergent-solubilized receptor into liposomes. In the
      present study, we show that calcium increases specific binding of FSH to receptor
      in a concentration-related manner, and is associated with an increase (13.2-fold
      at 20 mM) in the affinity (Ka) of the receptor with no significant (P greater
      than 0.05) change in receptor concentration. Treatment of the light membrane
      fraction with monodansylcadaverine (MDC, 1 mM), a specific inhibitor of TGase,
      did not affect specific binding of FSH, but resulted in only a 3.9-fold increase
      in Ka at 20 mM calcium with no change in receptor concentration. Specific binding
      of FSH to receptor at 4 degrees C was also enhanced by calcium. Scatchard
      analysis of competitive binding inhibition data showed a Ka at 20 mM calcium
      similar to that observed with MDC. Dissociation of [125I]hFSH-receptor complexes
      formed at 30 degrees C in the presence of calcium was significantly less than
      dissociation of complexes formed at 30 degrees C in the absence of calcium. When
      [125I]hFSH-receptor complexes were formed at 30 degrees C in the presence of
      calcium and dissociated in calcium-deficient buffer, dissociation increased 3
      fold. Similar results were obtained in the presence of MDC.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1359985
TI  - Regulation of gene transcription and proliferation by parathyroid hormone is
      blocked in mutant osteoblastic cells resistant to cyclic AMP.
AB  - We employed a cyclic AMP-resistant subclone of UMR 106-01 osteoblastic
      osteosarcoma cells (UMR 4-7) with a regulated, dominant-negative mutation of
      cyclic AMP-dependent protein kinase (PK-A), to examine the mechanism(s) whereby
      parathyroid hormone (PTH) regulates growth of these cells. Expression of a
      transiently transfected CAT reporter gene controlled by the cAMP response element
      of the rat somatostatin gene ('SST-CAT') was used to monitor PK-A activation in
      intact cells. Agonist-stimulated SST-CAT expression was specific for agents known
      to activate adenylate cyclase, required an intact cAMP response element and was
      specifically blocked following induction of the mutant cAMP-resistant phenotype
      in UMR 4-7 cells. Inhibition of the proliferation of UMR 106-01 cells by PTH,
      which is mimicked by forskolin and 8-bromo-cAMP, was blocked completely in mutant
      cyclic AMP-resistant UMR 4-7 cells. We conclude that control of proliferation in
      UMR 106-01 cells by PTH involves the cAMP messenger system and requires
      activation of PK-A.

PMID- 1359986
TI  - Lack of feedback inhibition of insulin secretion in denervated human pancreas.
AB  - In this study, pancreas transplantation is used as a clinical model of pancreas
      denervation in humans. To assess the role of innervation on the feedback
      autoinhibition of insulin secretion, we studied four groups of subjects--group 1:
      16 patients with combined pancreas and kidney transplantation (plasma glucose =
      5.1 mM, HbA1c = 6.4%, creatinine = 86 mM); group 2: 8 patients with chronic
      uveitis on the same immunosuppressive therapy as transplanted patients (12 mg/day
      prednisone, 5 mg.kg-1.day-1 CsA); group 3: 4 uremic, nondiabetic patients in
      chronic hemodialysis; group 4: 7 normal, nondiabetic control subjects. The
      following means were used to study the groups: 1) a two-step hyperinsulinemic
      euglycemic clamp (insulin infusion rate = 1 mU and 5 mU.kg-1.min-1); and 2) a 0.3
      mU.kg-1.min-1 hypoglycemic clamp (steady-state plasma glucose = 3.1 mM). Basal
      plasma-free IRI (84 +/- 6, 42 +/- 12, 72 +/- 12, and 30 +/- 6 pM in groups 1, 2,
      3, and 4, respectively), basal C-peptide (0.79 +/- 0.05, 0.66 +/- 0.05, 3.04 +/-
      0.20, and 0.59 +/- 0.06 nM in groups 1, 2, 3, and 4, respectively), and glucagon
      (105 +/- 13, 69 +/- 4, 171 +/- 10, and 71 +/- 5 pg/ml in groups 1, 2, 3, and 4,
      respectively) were increased in groups 1 and 3 with respect to groups 2 and 4 (P
      < 0.01). During euglycemic hyperinsulinemia, plasma C-peptide decreased by 45,
      20, and 44% in groups 2, 3, and 4, respectively, but showed no significant change
      from the basal in patients with transplanted pancreases.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1359988
TI  - Homeoboxes in flatworms.
AB  - A search for homeobox-containing genes was done in the genome of a primitive
      metazoan, the parasitic tapeworm Echinococcus granulosus. Five different
      homeoboxes were isolated, none of them belonging to the classical Antennapedia
      type. Three of the homeodomains are similar to those from the Drosophila
      melanogaster NK-type genes. The fourth homeodomain shares extensive identity with
      that of the recently reported homeobox-containing gene goosecoid from Xenopus
      laevis. The third helix (the recognition helix) of the fifth isolated homeodomain
      is identical to that of the Xlim-1 gene of X. laevis and the lin11 gene of
      Caenorharbditis elegans. Using PCR, some Antennapedia-type homeoboxes were cloned
      from the genome of two other Platyhelminthes, Dugesia tigrina (planaria) and
      Fasciola hepatica. These data suggest that, contrary to what is found for the
      majority of the more complex metazoans, Platyhelminthes contain few homeobox
      genes belonging to the Antennapedia-type.

PMID- 1359987
TI  - Linkage analysis of GLUT1 (HepG2) and GLUT2 (liver/islet) genes in familial
      NIDDM.
AB  - Familial NIDDM probably results from combined inherited defects of insulin
      secretion and action. Members of the facilitative glucose transporter family are
      strong candidates for both defects, and RFLPs for both GLUT1 (erythrocyte) and
      GLUT2 (liver/islet) genes have been associated with NIDDM in some populations. To
      test the hypothesis that GLUT1 and GLUT2 mutations contribute to the inherited
      predisposition to NIDDM, we examined linkage of these loci with NIDDM in 18 large
      Utah white pedigrees (two and three generation) ascertained for > or = 2 NIDDM
      siblings. We used two RFLPs detected with Xba1 and Stu1 for the GLUT1
      transporter. For the GLUT2 (liver/beta-cell) transporter gene, we used an RFLP
      detected with EcoR1 and a highly polymorphic (6-allele) dinucleotide
      (microsatellite) repeat. Analysis was performed with the MLINK program of the
      LINKAGE package. We tested four models for each locus: dominant and recessive,
      with IGT alternately considered as unknown affection status, or affected if IGT
      was diagnosed < or = 45 yr of age and unknown if > 45 yr. Disease gene
      frequencies were chosen to give approximate disease prevalence in American whites
      (q = 0.03, dominant; q = 0.25, recessive). Linkage of GLUT1 and NIDDM was
      strongly and significantly rejected under all models, with total (pooled) LOD
      scores of -5.7 to -8.9, indicating > 500,000:1 odds against linkage. Pooled LOD
      scores were significantly negative (< -2.0, or 100:1 odds against linkage) to a
      recombination fraction of > 5%. No heterogeneity was apparent. Analysis of GLUT2
      gave similar results, with LOD scores of < -4.0 under each model, indicating at
      least 10,000:1 odds against linkage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359989
TI  - The 28S ribosomal RNA-encoding gene of Hymenoptera: inserted sequences in the
      retrotransposon-rich regions.
AB  - The genomes of two parasitoid wasps, Diadromus pulchellus and Eupelmus vuilleti,
      and the honey bee, Apis mellifera, contain few interspersed repeated sequences
      corresponding to transposons (Tn). This suggests that the genomic organisation of
      Hymenoptera could be due to the elimination of deleterious Tn in haploid males.
      We have used restriction-fragment length polymorphism analysis to show that
      nondeleterious Tn are present in the DNA (rDNA) encoding ribosomal RNA of twelve
      species of Hymenoptera. Sequence analysis of the 28S rDNA type-I and type-II
      insertion-rich regions of 80 species showed that this region is very highly
      conserved (95.8%). A consensus sequence and restriction map of the rDNA region
      were established. These sequence data were used to develop a strategy for
      detecting inserted elements in the rDNA fragments containing type-I or type-II
      insertion sites, and this strategy was used to screen twelve hymenopteran species
      and four non-Hymenoptera control species. The rDNA fragments from the Hymenoptera
      and control species contained inserted sequences in the area where type-I and
      type-II elements are inserted in the 28S rDNA retrotransposon-rich region of
      Diptera and Lepidoptera. The hymenopteran genomes therefore appear to contain
      repeated elements, the mobility and nature of which remain to be determined.

PMID- 1359990
TI  - Sequence of a novel chicken genomic DNA fragment that hybridizes to the murine
      Hox-3.1 homeobox.
AB  - A chicken genomic library was screened for novel homeobox-like elements. We
      describe a chicken genomic DNA fragment which hybridizes to the murine Hox-3.1
      homeobox. The fragment is a single-copy sequence which seems to be transcribed
      without spacial or temporal restrictions. The sequence presented here is not
      representative of anything yet in the databases; however, it contains a very
      probable open reading frame which would encode a peptide slightly homologous to
      the Hox-3.1 protein.

PMID- 1359991
TI  - Growth factors in the gastrointestinal tract.

PMID- 1359992
TI  - Different DNA changes in primary and recurrent hepatocellular carcinoma.
AB  - DNA restriction fragment length polymorphism analysis was carried out on a
      primary and recurrent hepatocellular carcinoma in a hepatitis B virus negative
      patient. For the primary tumour, allele losses were found on the short arm of
      chromosome 17 (probe: p144-D6, 17p13) and the long arm of chromosome 5 with the
      probe Lambda MS8 (5q35-qter); other probes showed either no allele loss or a non
      informative pattern. The recurrent cancer also showed allele loss with p144-D6,
      but not with Lambda MS8. In addition, the recurrent tumour had allele losses with
      Lambda MS43 (12q24.3-qter), pYNZ22 (17p13), and DNA rearrangement revealed by the
      probe Lambda MS32 (1q42-43), a pattern not seen in the primary lesion. These
      results indicate that the second hepatocellular carcinoma was of independent
      clonality and probably represents a de novo neoplasm rather than a recurrence.

PMID- 1359993
TI  - [Modification of classical drug receptor mechanisms].
AB  - It is generally accepted that full and partial agonists interact with the same
      receptors according to the classical receptor mechanisms. We have modified the
      drug receptor mechanisms of M3-, alpha 1- and beta-receptors. Among the
      muscarinic receptors, there are two subtypes of M3-cholinoceptors,
      propylbenzilylcholine mustard (PrBCM)-sensitive receptors and (PrBCM)-resistant
      ones. Full agonists contract the guinea pig ileum through both types of
      cholinoceptors, while the partial agonists produce contractions through only the
      PrBCM-sensitive receptors. Two subtypes of alpha 1-adrenoceptors, alpha 1A and
      alpha 1B, were demonstrated in some arteries. Full agonists contracted the rabbit
      aorta through both the alpha 1A- and alpha 1B-adrenoceptors, while the partial
      agonists mediated contraction through only the alpha 1A-adrenoceptors. beta
      Chloroethylamines (PrBCM and chloroethylclonidine) can discriminate the subtype
      of M3- or alpha 1-receptors in the presence of GTP. beta-Adrenoceptors have two
      different types of binding sites, high and low affinity sites. The competitive
      antagonistic effect of the partial agonist is due to their ability to compete
      with the full agonists for the high affinity site, while the partial agonists
      interact with the low affinity site to induce the beta-adrenergic effect. A
      regional difference in alpha 1-adrenoceptor mechanisms was discussed. The potency
      of norepinephrine in veins is related to alpha 1-adrenoceptor densities. In
      contrast, the potency of norepinephrine is linearly related to the agonist
      dissociation constant. This discrepancy suggests a qualitative difference between
      alpha 1-adrenoceptor mechanisms in the veins and arteries.

PMID- 1359994
TI  - Hepatitis C virus and porphyria cutanea tarda: evidence of a strong association.
AB  - Porphyria cutanea tarda in human beings is believed to be due to reduced hepatic
      uroporphyrinogen decarboxylase activity. However, extrinsic factors such as
      alcohol abuse and drug intake are required for clinical manifestation of the
      disease. In addition to typical cutaneous lesions, patients with porphyria
      cutanea tarda usually have chronic liver disease and moderate iron overload. Of
      74 Italian patients with porphyria cutanea tarda, hepatitis C virus antibodies
      were detected in 76% by enzyme-linked immunoassay and in 82% by recombinant
      immunoblot assay. Viral genome, studied with nested polymerase chain reaction,
      was found in the sera of 49 subjects--47 positive and 2 indeterminate on
      recombinant immunoblot assay. Five percent of the patients were HBsAg-positive,
      and about 40% had had past hepatitis B contacts. Alcohol abuse was present in
      38%. Liver biopsies performed in 42 patients showed chronic persistent hepatitis
      in 7 patients, chronic active hepatitis in 22 patients, fibrosis in three
      patients and cirrhosis in 10 patients. Hepatitis C virus antibody was detected in
      100% of patients with chronic active hepatitis and in about 80% of all other
      groups. Alcohol abuse was more frequent in patients with cirrhosis (80%) than in
      the other groups. In Italian patients with porphyria cutanea tarda, the
      prevalence of hepatitis C virus infection was very high, comparable to that in
      non-A, non-B hepatitis and high-risk patient groups. Hepatitis C virus is
      probably the main pathogenetic factor of the liver disease of patients with
      porphyria cutanea tarda.

PMID- 1359995
TI  - Susceptibility to primary biliary cirrhosis is associated with the HLA-DR8
      DQB1*0402 haplotype.
AB  - In studies to date seeking associations between human leukocyte antigens (HLA)
      and primary biliary cirrhosis, no class I association but several different class
      II associations have been described. The aims of this study were to reassess the
      DR associations in primary biliary cirrhosis and to examine for the first time
      the role of DQB. DRB genotypes were determined on standard Taq1 restriction
      fragment-length polymorphism analysis in 159 white northern European patients
      with the disease and 162 racially matched local controls. Polymerase chain
      reaction gene amplification and sequence-specific oligonucleotide analysis were
      used to determine DQB genotypes in 89 patients and 181 controls. An increased
      frequency of human leukocyte antigen DR8 was observed in the patient group (11%
      vs 4%; relative risk = 3.3; p < 0.01). Although we saw an increased frequency of
      the DQB1*0402 allele (11% vs. 3%; relative risk = 3.5; p < 0.025), this was not
      significant after correction for multiple testing. The strongest association was
      with the two-locus haplotype DR8-DQB1*0402 (11% vs. 2.2%; relative risk 5.5; p <
      0.001). The DRB data reported here confirm the findings of previous studies,
      although the described association with DR8 is considerably weaker. The weak
      genetic contribution of human leukocyte antigen in the susceptibility to primary
      biliary cirrhosis is in contrast to its role in other autoimmune liver diseases.

PMID- 1359996
TI  - Cytoprotective effect of somatostatin in a rat model of hepatic ischemic
      reperfusion.
AB  - To evaluate the possible cytoprotective effect of somatostatin in hepatic
      ischemic reperfusion injury we used 75 adult male Wistar rats randomly separated
      into four groups. The rats in group 1 underwent sham operations, and those in
      group 2 underwent resection of the median and left lateral lobes. The rats in
      group 3 underwent a 90-min period of ischemia of the right lateral lobe, which we
      induced by temporarily occluding the right portal vein and the hepatic artery. On
      restoration of flow to the right lateral lobe, the median and left lateral lobes
      (about 80% of total liver mass) were excised (and later assayed for thymidine
      kinase basal activity). The rats in group 4 were given the same treatment as
      group 3 rats except that a saline solution of somatostatin was infused at a rate
      of 2 micrograms/min starting at laparotomy and lasting 24 hr. The rats in groups
      1, 2 and 3 were infused with saline. Rats in groups 2, 3 and 4 were randomly
      assigned to two subgroups; one of these subgroups was observed until spontaneous
      death, and rats in the other group were killed 24 hr after the procedure for
      obtaining peripheral blood and liver samples. Somatostatin infusion improved the
      animals' survival rates from 0% (group 3) to 60% (group 4) (p < 0.05) and
      decreased bilirubin levels (0.78 +/- 0.17 mg/dl, n = 15 [group 4] vs. 1.69 +/-
      0.04 mg/dl, n = 15 [group 3]; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1359997
TI  - Valid estimation of IL2 secretion by PHA-stimulated T-cell clones absolutely
      requires the use of anti-CD25 monoclonal antibody to prevent IL2 consumption.
AB  - A major problem encountered for quantification of IL2 production by stimulated T
      cells is its simultaneous consumption by these activated cells. In the present
      study, 40 T-cell clones (TCC) derived from normal peripheral blood, hyperplastic
      lymph nodes (LN) or lymph nodes involved by malignant lymphomas, were studied for
      their ability to produce IL2. When supernatants were generated in the presence of
      20% fetal calf serum (FCS), no IL2 could be detected for 22 of the 40 TCC,
      whereas very low levels were found for the 18 other TCC (mean value 31 pg/ml;
      range from 10 pg/ml to 114 pg/ml); in contrast, when conditioned media were
      produced with reduced amounts of FCS (final concentration, 1%) as well as in the
      presence of an anti-CD25 monoclonal antibody (final concentration, 50
      micrograms/ml), all TCC were found to release IL2, and very high quantities of
      this lymphokine were measured (mean value: 11,387 pg/ml; range, from 250 pg/ml to
      37,000 pg/ml). Consequently, inhibition of IL2 consumption by PHA-stimulated TCC
      seems to be an absolute requirement for estimating the true capacity of T cells
      to produce this lymphokine.

PMID- 1359998
TI  - Bronchodilation and beta 2-selectivity of broxaterol in asthmatics: a crossover,
      single-blind, terbutaline- and placebo-controlled study.
AB  - To investigate the beta 2-receptor selectivity of a new beta 2-adrenoceptor
      agonist, broxaterol, we compared the respiratory and cardiovascular effects of
      this compound with those of terbutaline and placebo. Twelve asthmatic patients
      were evaluated in a randomized, single blind, crossover study. A single dose of
      each study treatment (broxaterol 400 micrograms and terbutaline 500 micrograms
      was administered with metered dose inhalers. Measurements of lung function (vital
      capacity, forced expiratory volume in one second, airway resistance and specific
      airway conductance), heart rate and systolic/diastolic blood pressure were
      performed before and at 15, 30, 60, 120, 240 and 360 min after each study
      treatment. No significant difference was observed between broxaterol and
      terbutaline in VC, FEV1 and Raw changes, although a greater and significant
      increase in sGaw was found only with broxaterol. Significant increases in heart
      rate and systolic blood pressure were observed only with terbutaline. The results
      of this study suggest that broxaterol can promote a greater bronchodilator effect
      with less cardiovascular side effects than terbutaline, probably through a
      greater beta 2-receptor selectivity.

PMID- 1359999
TI  - Synthesis and opioid activity of 2-substituted dynorphin A-(1-13) amide
      analogues.
AB  - A series of 2-substituted dynorphin A-(1-13) amide (Dyn A-(1-13)NH2) analogues
      was prepared by solid phase peptide synthesis and evaluated for opioid receptor
      affinities in radioligand binding assays and for opioid activity in the guinea
      pig ileum (GPI) assay. Amino acid substitution at the 2 position produced marked
      differences in both opioid receptor affinities and potency in the GPI assay; Ki
      values for the analogues in the radioligand binding assays and IC50 values in the
      GPI assay varied over three to four orders of magnitude. The parent peptide, Dyn
      A-(1-13)NH2, exhibited the greatest affinity and selectivity for kappa receptors
      and was the most potent peptide examined in the GPI assay. The most important
      determinant of opioid receptor selectivity and opioid potency for the synthetic
      analogues was the stereochemistry of the amino acid at the 2 position. Except for
      [D-Lys2]Dyn A-(1-13)NH2 in the kappa receptor binding assay, the analogues
      containing a D-amino acid at position 2 were much more potent in all of the
      assays than their corresponding isomers containing an L-amino acid at this
      position. The L-amino acid-substituted analogues generally retained some
      selectivity for kappa opioid receptors. The more potent derivatives with a D
      amino acid in position 2, however, preferentially interacted with mu opioid
      receptors. Introduction of a positively charged amino acid into the 2 position
      generally decreased opioid receptor affinities and potency in the GPI assay.

PMID- 1360000
TI  - International Educational Symposium on Training and Education of Residents in
      Radiation Oncology. Philadelphia, April 5-6, 1991.

PMID- 1360001
TI  - Skeletal muscle and liver glutathione homeostasis in response to training,
      exercise, and immobilization.
AB  - Female beagle dogs were treadmill trained 40 km/day at 5.5-6.8 km/h, 15% upgrade,
      5 days/wk for 55 wk. With training, hepatic and red gastrocnemius (RG) total
      glutathione increased, glutathione peroxidase (GPX) and glutathione reductase
      (GRD) increased in all the leg muscles studied, and hepatic glutathione S
      transferase (GST) activity increased. Joint immobilization (11 wk) did not affect
      GPX, GRD, and GST of RG, but total glutathione decreased. Male Han Wistar rats
      were treadmill trained 2 h/day at 2.1 km/h, 5 days/wk for 8 wk. With training,
      hepatic total glutathione and leg muscle GPX increased but GRD of RG decreased,
      perhaps because of an increased muscle flavo-protein breakdown during exhaustive
      training. gamma-Glutamyl transpeptidase was higher in the trained leg muscles.
      Exhaustive exercise decreased muscle gamma-glutamyl transpeptidase of only
      control leg muscle, depleted muscle (lesser extent in trained rats) and liver
      total glutathione of both groups, decreased GRD only in untrained RG, and
      increased hepatic GST. Endurance training elevated the antioxidant and detoxicant
      status of muscle and liver, respectively.

PMID- 1360002
TI  - Role of leukocyte CD11/CD18 complex in endotoxic and septic shock in rabbits.
AB  - Two models of sepsis were investigated using rabbits. In the first model, rabbits
      given lipopolysaccharide (LPS) were treated with saline (group II) or CD18
      monoclonal antibody (MAb) 60.3 (group III). Group I animals received no LPS.
      Cardiac output was maintained by infusion of lactated Ringer solution with group
      II (95 +/- 68 ml/kg) requiring significantly more than group I (0 +/- 0 ml/kg) or
      group III (39 +/- 27 ml/kg). Lung permeability indexes in groups II (median
      0.002, range 0.023) and III (median 0.0035, range 0.053) were not different but
      were significantly greater than group I (median 0.0007, range 0.001). In the
      second model, peritonitis was produced by devascularizing the appendix, leaving
      it in situ for 19 h, and then performing an appendectomy. Saline or MAb 60.3
      treatment was at appendectomy and every 12 h for 3 days. Survival was
      significantly greater in the MAb 60.3-treated group at day 10 (90 vs. 40%). Lung
      permeability was increased at day 2 and was not different between groups. Day 1
      fluid requirements were greater in the saline-treated group. These data are
      consistent with MAb 60.3 protection of systemic but not pulmonary circulation in
      two models of sepsis.

PMID- 1360003
TI  - Cardiac secretion of atrial natriuretic factor with exercise in chronic
      congestive heart failure patients.
AB  - We have previously reported a fivefold increase of plasma atrial natriuretic
      factor (ANF) in patients with congestive heart failure (CHF) compared with normal
      subjects. However, given the marked increase of ANF under basal conditions, the
      extent to which ANF secretion can further increase under physiological stress is
      not been clarified in CHF. We therefore evaluated ANF secretion during ergometric
      exercise in 11 patients with CHF, with peripheral venous ANF samples obtained at
      rest and peak exercise. In seven patients, simultaneous peripheral venous and
      right ventricular ANF samples were obtained to estimate myocardial ANF secretion.
      Hemodynamic characteristics of exercise included a significant increase of heart
      rate, mean arterial pressure, and cardiac output (all P < 0.01); reduction of
      systemic vascular resistance (P < 0.001); and increase of right atrial and
      pulmonary wedge pressures (P < 0.001). ANF was abnormally elevated at baseline
      (108 +/- 58 fmol/ml) yet increased further to 183 +/- 86 fmol/ml with exercise (P
      < 0.003). A step-up of right ventricular ANF, particularly during exercise, was
      consistent with active myocardial secretion, despite elevated baseline ANF
      levels.

PMID- 1360004
TI  - Differential expression of a Clostridium acetobutylicum antisense RNA:
      implications for regulation of glutamine synthetase.
AB  - The Clostridium acetobutylicum glutamine synthetase (GS) DNA region is
      characterized by a downstream promoter, P3, oriented toward the glnA gene, which
      controls the transcription of an RNA complementary to the start of the glnA mRNA.
      Expression of the predicted 43-base antisense RNA was demonstrated in C.
      acetobutylicum and Escherichia coli cells containing the cloned glnA DNA.
      Antisense RNA transcription from P3 was not regulated by nitrogen in E. coli
      cells, but the expression of antisense RNA was associated with decreased levels
      of GS activity. In C. acetobutylicum, GS activity and the transcription of glnA
      mRNA and antisense RNA were regulated by nitrogen. GS activity and glnA mRNA were
      repressed in cells grown in nitrogen-rich medium. Repression ratios for GS
      activity varied from 1.6 to 9.0, depending on the sampling time. The relative
      number of glnA transcripts was approximately 25% lower in cells grown for 72 h in
      nitrogen-rich medium than in cells grown in nitrogen-limiting medium. This
      finding contrasted with the expression of antisense RNA, which was repressed in
      nitrogen-limiting medium but induced in nitrogen-rich medium. The relative number
      of antisense RNA transcripts was increased approximately sixfold in cells grown
      in nitrogen-rich medium. There was a 1.6-fold excess of antisense RNA over glnA
      mRNA under conditions that repressed GS activity. Under conditions that induced
      GS activity, glnA mRNA transcripts exceeded antisense RNA transcripts by
      fivefold.

PMID- 1360005
TI  - Identification of ancillary fim genes affecting fimA expression in Salmonella
      typhimurium.
AB  - Regulation of the gene, fimA, encoding the major fimbrial subunit of S.
      typhimurium S6704 was examined by using a lambda fimA-lacZ lysogen.
      Transformation of the lambda fimA-lacZ lysogen with various derivatives of the
      recombinant plasmid that encodes type 1 fimbrial expression, pISF101, indicated
      that two regions of this plasmid alter beta-galactosidase production. One plasmid
      is a deletion resulting in the loss of a 28-kDa polypeptide downstream of fimA,
      while the other plasmid encodes a 24- and a 27-kDa polypeptide. Northern (RNA)
      blot analyses indicated that the steady-state fimA mRNA levels of these
      transformants were high. In addition, phenotypic expression of type 1 fimbriae by
      agar-grown cultures is observed only in those transformants bearing plasmids
      which show increased beta-galactosidase and fimA mRNA levels.

PMID- 1360006
TI  - Amplification fragment length polymorphism in Brucella strains by use of
      polymerase chain reaction with arbitrary primers.
AB  - DNA heterogeneity among members of the genus Brucella was demonstrated with the
      arbitrarily primed polymerase chain reaction (AP-PCR). Simple, reproducible
      genomic fingerprints from DNA of 25 different Brucella strains were generated
      with five arbitrarily chosen primers, alone and in pairs, with the PCR. Reaction
      conditions were optimized for each primer. Several DNA segments were amplified in
      each sample with all of the primers. PCR products that are not shared among all
      strains act as polymorphic markers. Polymorphism was apparent for each primer.
      The Brucella strains can be distinguished according to the banding patterns of
      their amplified DNA on agarose gels, and the differences can be diagnostic of
      specific strains. To determine genetic relatedness among the Brucella strains,
      similarity coefficients were calculated. Statistical analysis of the similarity
      coefficients revealed the degrees of relatedness among strains of the genus
      Brucella.

PMID- 1360007
TI  - Map position of the glnE gene from Escherichia coli.

PMID- 1360008
TI  - Dopaminergic inhibition of DNA synthesis in pituitary tumor cells is associated
      with phosphotyrosine phosphatase activity.
AB  - Dopaminergic D2 receptor agonists, such as bromocriptine, are potent anti
      proliferative agents in the treatment of human pituitary adenomas. We have
      reproduced the anti-proliferative effect of dopamine in an established pituitary
      cell line stably transfected with the rat D2 dopamine receptor cDNA. We found
      that dopaminergic inhibition of DNA synthesis parallels the stimulation of a
      phosphotyrosine phosphatase activity. Both actions are blocked by pertussis toxin
      and by the phosphotyrosine phosphatase inhibitor, vanadate. We suggest that the
      anti-proliferative action of dopamine is mediated, at least in part, by the
      dopaminergic stimulation of a phosphotyrosine phosphatase.

PMID- 1360009
TI  - Characterization and developmental expression of chick aortic lysyl oxidase.
AB  - The complete primary structure of chick lysyl oxidase was determined by
      recombinant DNA techniques. The nucleotide sequence of contiguous chick lysyl
      oxidase cDNA clones contained an open reading frame of 1260 bases which encodes a
      predicted protein of 420 amino acid residues (48,150 Da). In comparison to the
      deduced primary structure of rat lysyl oxidase, the chick enzyme is larger in
      size and exhibits a strong conservation of sequence within the latter two thirds
      of the molecule (92% identity) and a high degree of divergence in the first 150
      amino acid residues (60% identity allowing for several insertions in both
      sequences). The developmental steady-state levels of lysyl oxidase mRNA together
      with the mRNAs encoding two of the enzyme's substrates (tropoelastin and type I
      collagen) increased between 8 and 16 days of embryonic development. Although
      levels of lysyl oxidase mRNA increased during aortic embryogenesis, the specific
      activity of the enzyme remained fairly constant suggesting that lysyl oxidase
      activity increases in direct proportion to total protein synthesis and cell
      number. In situ hybridization showed that the spatial expressions of lysyl
      oxidase and tropoelastin transcripts differ suggesting that the enzyme and
      substrate genes are differentially regulated within the cells of the arterial
      wall.

PMID- 1360011
TI  - Inorganic pyrophosphatase from bovine retinal rod outer segments.
AB  - Rod outer segments from bovine retina contain a higher level of intracellular
      inorganic pyrophosphatase (EC 3.6.1.1) activity than has been found in any other
      mammalian tissue; the specific activity in extracts of soluble outer segment
      proteins is more than 6-fold higher than in extracts from bovine liver and more
      than 24-fold higher than in skeletal muscle extracts. This high activity may be
      necessary to keep inorganic pyrophosphate concentrations low in the face of the
      high rates of pyrophosphate production that accompany the cGMP flux driving
      phototransduction. We have begun to explore the role of inorganic pyrophosphatase
      in photoreceptor cGMP metabolism by 1) studying the kinetic properties of this
      enzyme and its interactions with divalent metal ions and anionic inhibitors, 2)
      purifying it and studying its size and subunit composition, and 3) examining the
      effects of pyrophosphate on rod outer segment guanylyl cyclase. Km for magnesium
      pyrophosphate was 0.9-1.5 microM, and the purified enzyme hydrolyzed > 885 mumol
      of PPi min-1 mg-1. The enzyme appears to be a homodimer of 36-kilodalton subunits
      when analyzed by gel electrophoresis and density gradient centrifugation,
      implying that kcat = 10(3) s-1, and kcat/Km = 0.7-1 x 10(9) M-1 s-1. The enzyme
      was inhibited by Ca2+ at submicromolar levels: 28% inhibition was observed at 138
      nM [Ca2+], and 53% inhibition at 700 nM [Ca2+]. Imidodiphosphate acted as a
      competitive inhibitor, with Ki = 1.2 microM, and fluoride inhibited half
      maximally approximately 20 microM. Inhibition studies on rod outer segment
      guanylyl cyclase confirmed previous reports that pyrophosphate inhibits guanylyl
      cyclase, suggesting an essential role for inorganic pyrophosphatase in
      maintaining cGMP metabolism.

PMID- 1360010
TI  - Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not
      progesterone.
AB  - We expressed human MDR1 cDNA isolated from the human adrenal gland in porcine LLC
      PK1 cells. A highly polarized epithelium formed by LLC-GA5-COL300 cells that
      expressed human P-glycoprotein specifically on the apical surface showed a
      multidrug-resistant phenotype and had 8.3-, 3.4-, and 6.5-fold higher net basal
      to apical transport of 3H-labeled cortisol, aldosterone, and dexamethasone,
      respectively, compared with host cells. But progesterone was not transported,
      although it inhibited azidopine photoaffinity labeling of human P-glycoprotein
      and increased the sensitivity of multidrug-resistant cells to vinblastine. An
      excess of progesterone inhibited the transepithelial transport of cortisol by P
      glycoprotein. These results suggest that cortisol and aldosterone are
      physiological substrates for P-glycoprotein in the human adrenal cortex and that
      substances that efficiently bind to P-glycoprotein are not necessarily
      transported by P-glycoprotein.

PMID- 1360012
TI  - Characterization of a stable, reactivatable complex between chaperonin 60 and
      mitochondrial rhodanese.
AB  - Efficient formation of the cpn60-rhodanese complex can be achieved by mixing
      unfolded rhodanese with excess cpn60 at low temperature. By employing these
      conditions, a stable and highly reactivatable complex is formed. The complex is
      not formed when native enzyme is used. Concentrations of NaCl, as high as 0.75 M,
      do not have any effect on the formation or disruption of the binary complex.
      cpn60-bound rhodanese contains an exposed hydrophobic surface, as detected by the
      binding of the fluorescent reporter, 1-anilinonaphthalene-8-sulfonic acid. The
      intrinsic fluorescence of cpn60-bound rhodanese reports that the average
      tryptophan is in an intermediate environment between that found in unfolded and
      native states. This form of rhodanese has an accessibility to quenching by
      acrylamide or iodide that is intermediate between the unfolded and native forms
      of the enzyme. Protease susceptibility studies show that rhodanese bound to cpn60
      exhibits a trypsin digestion pattern similar to the native enzyme, although it is
      more rapidly proteolyzed. The results suggest that the conformation of cpn60
      bound rhodanese resembles a native-like conformation, but with increased
      flexibility. Further, only intact rhodanese or enzyme lacking its N-terminal
      sequence can interact with cpn60 and form a stable binary complex. The protein
      fragment corresponding to the rhodanese N-terminal sequence did not form part of
      a stable complex with cpn60.

PMID- 1360016
TI  - Proceedings of the ESHRE Campus Workshop on Reproductive Medicine. Bonn, Germany,
      March 18-22, 1991.

PMID- 1360013
TI  - Long-term sensitization training in Aplysia leads to an increase in the
      expression of BiP, the major protein chaperon of the ER.
AB  - Long-term memory for sensitization of the gill- and siphon-withdrawal reflexes in
      Aplysia californica requires RNA and protein synthesis. These long-term
      behavioral changes are accompanied by long-term facilitation of the synaptic
      connections between the gill and siphon sensory and motor neurons, which are
      similarly dependent on transcription and translation. In addition to showing an
      increase in over-all protein synthesis, long-term facilitation is associated with
      changes in the expression of specific early, intermediate, and late proteins, and
      with the growth of new synaptic connections between the sensory and motor neurons
      of the reflex. We previously focused on early proteins and have identified four
      proteins as members of the immunoglobulin family of cell adhesion molecules
      related to NCAM and fasciclin II. We have now cloned the cDNA corresponding to
      one of the late proteins, and identified it as the Aplysia homolog of BiP, an ER
      resident protein involved in the folding and assembly of secretory and membrane
      proteins. Behavioral training increases the steady-state level of BiP mRNA in the
      sensory neurons. The increase in the synthesis of BiP protein is first detected 3
      h after the onset of facilitation, when the increase in overall protein synthesis
      reaches its peak and the formation of new synaptic terminals becomes apparent.
      These findings suggest that the chaperon function of BiP might serve to fold
      proteins and assemble protein complexes necessary for the structural changes
      characteristic of long-term memory.

PMID- 1360014
TI  - Poly(A) RNA codistribution with microfilaments: evaluation by in situ
      hybridization and quantitative digital imaging microscopy.
AB  - The distribution of poly(A) RNA has been visualized in single cells using high
      resolution fluorescent in situ hybridization. Digital imaging microscopy was used
      to quantitate the signal in various cellular compartments. Most of the poly(A)
      signal remained associated with the cellular filament systems after
      solubilization of membranes with Triton, dissociation of ribosomes with
      puromycin, and digestion of non-poly(A) RNA with ribonuclease A and T1. The actin
      filaments were shown to be the predominant cellular structural elements
      associating with the poly(A) because low doses of cytochalasin released about two
      thirds of the poly(A). An approach to assess the extent of colocalization of two
      images was devised using in situ hybridization to poly(A) in combination with
      probes for ribosomes, membranes, or F-actin. Digital imaging microscopy showed
      that most poly(A) spatially distributes most significantly with ribosomes,
      slightly less with F-actin, and least of all with membranes. The results suggest
      a mechanism for anchoring (and perhaps moving) much of the cellular mRNA
      utilizing the interaction between actin filaments and poly(A).

PMID- 1360015
TI  - Human aortic endothelial cells express the type I but not the type II receptor
      for interleukin-1 (IL-1).
AB  - Endothelial cells (EC) are very responsive to the proinflammatory cytokine
      interleukin-1 (IL-1). EC are induced by IL-1 to secrete chemotactic factors and
      to increase expression of cell surface adhesion molecules leading to increased
      leukocyte adhesion. Activated EC further contribute to the inflammatory response
      by secreting additional cytokines. IL-1 interacts with EC through high-affinity
      cell-surface receptors. However, the low number of receptors present on EC has
      made characterization difficult. Further, recent evidence has suggested diversity
      in the responses of EC from different regions of the vascular system. Interested
      in the effect of IL-1 on early atherosclerotic lesion formation, we have
      characterized the IL-1 receptors on human aortic endothelial cells (HAEC). Using
      a direct binding assay, we found that HAEC have 1,000-3,000 IL-1 receptors per
      cell and bind IL-1 alpha with a Kd of 3.5 x 10(-10) M. We found that a monoclonal
      antibody specific for the type I receptor completely blocks IL-1 alpha binding.
      The blocking antibody also completely inhibits the IL-1 induced increase in
      intracellular adhesion molecule 1 (ICAM-1) expression by HAEC. Using solution
      hybridization and ribonuclease protection with an antisense probe, a sensitive
      method for detection of low abundance mRNA species we found that HAEC as well as
      human umbilical vein EC (HUVEC) have significant levels of mRNA for the type I IL
      1 receptor. To test whether HAEC might also contain transcripts for the type II
      IL-1 receptor, we compared levels of mRNAs by polymerase chain reaction (PCR)
      amplification of cDNAs reverse-transcribed from total RNA. We found only
      transcripts for the type I receptor and not the type II receptor in HAEC. Based
      on this data, we conclude that aortic endothelial cells respond to IL-1 through
      the type I receptor.

PMID- 1360017
TI  - From controversy to resolution: bioequivalency of racemic drugs--a symposium on
      the dynamics, kinetics, bioequivalency, and analytical aspects of
      stereochemistry.

PMID- 1360018
TI  - Noradrenergic modulation of noxious heat-evoked fos-like immunoreactivity in the
      dorsal horn of the rat sacral spinal cord.
AB  - The tail-flick withdrawal reflex commonly is used to study spinal nociceptive
      mechanisms; noradrenergic agonists administered intrathecally inhibit the tail
      flick reflex in a dose-dependent manner. The objectives of the present study
      were: (1) to use fos-like immunoreactivity as a marker for neuronal activity to
      examine the population of neurons in the spinal cord dorsal horn that are engaged
      by activation of nociceptive tail afferents, and (2) to determine whether fos
      like immunoreactivity can be modulated by intrathecally administered alpha
      adrenoceptor agonists. Neurons demonstrating heat-evoked fos-like
      immunoreactivity were identified bilaterally in the sacral spinal cord in
      superficial and deep dorsal horn laminae. Heat-evoked fos-like immunoreactivity
      was inhibited dose-dependently by intrathecal norepinephrine (NE). The inhibition
      was attenuated significantly by: (1) phentolamine (PHEN), a nonselective alpha
      adrenoceptor antagonist; (2) yohimbine (YOH), an alpha-2 adrenoceptor antagonist;
      and (3) prazosin (PRAZ), an alpha-1 adrenoceptor antagonist. Thus, both spinal
      alpha-1 and alpha-2 adrenoceptors mediate the inhibition of heat-evoked fos-like
      immunoreactivity produced by intrathecal NE. ST-91, an alpha-2 adrenoceptor
      agonist, also inhibited significantly the expression of fos-like
      immunoreactivity; the inhibition was antagonized by YOH. In the absence of
      noxious heat, intrathecal NE dose-dependently evoked the expression of fos-like
      immunoreactivity in the superficial dorsal horn, which was antagonized by PHEN
      and PRAZ, but not by YOH, suggesting that the effect is mediated by spinal alpha
      1 adrenoceptors.

PMID- 1360019
TI  - [The pattern of the expression of homeo box-containing genes in the mesenchyme of
      the mammalian limb bud as a coordinate network for subsequent morphogenetic
      processes].
AB  - Hypothesis is developed about mechanisms of determination of limb bud of mammals
      as a result of expression of homeo box containing genes (hox genes) of known up
      to date four hox families. Spatial pattern of the expression plays a role of
      coordinate system for subsequent processes of morphogenesis and differentiation
      of the limbs. Propositions of the hypothesis are realized in a computer dynamic
      model. The results of modeling are compared with known data on features of the
      expression of hox genes in the mesenchyme of developing limb buds in mammals and
      birds.

PMID- 1360020
TI  - Prolactin bioassay and hyperprolactinemia.
AB  - The Nb2 rat lymphoma bioassay (BA) for prolactin (PRL) was performed in 26
      subjects with hyperprolactinemia, 17 of whom had radiologic evidence of a
      pituitary adenoma. All subjects were treated with the long acting dopamine
      agonist CV 205-502. The radioimmunoassay (RIA) PRL significantly decreased with
      treatment but the BA/RIA PRL remained essentially the same, indicating that the
      relative bioactivity was unaffected.

PMID- 1360021
TI  - The management of hyperthyroidism due to Graves' disease in the former USSR in
      1991: results of a survey.
AB  - A survey of the current management of Graves' disease was performed in the USSR
      among members of All Union Endocrine Society. The questionnaire was based on the
      format used previously for a survey of members of European Thyroid Association.
      The aim of a similar survey in the USSR was to obtain a comprehensive pattern of
      management of Graves' disease in Soviet endocrinology clinics and to compare
      medical attitudes in the former USSR to those in other European countries. One
      hundred and twenty questionnaires were mailed with 55 returned (46%). The
      responses originated from 33 cities, representing major endocrinology centers of
      the former Soviet Republics. Initial diagnosis was conducted both in hospitals
      (55%) and ambulatory care settings (45%). Thyroid scintigraphy was requested by
      42.3% of the respondents; a majority of them (90%) used 131I. Thyroid
      ultrasonography was performed in more than 50% of cases. Measurements of
      cholesterol, total T4 and T3 were the most frequent laboratory tests requested to
      confirm the diagnosis. For the treatment with ATD, methimazole was the exclusive
      choice (PTU is not currently in use in the USSR). Beta-blocking agents were
      prescribed by a majority of respondents. For the long term treatment, a
      combination procedure of MMI and thyroid hormones was clearly preferred by almost
      3/4 of the respondents. A fixed period of treatment was preferred by 62% of the
      respondents, with a duration of therapy of 18-24 months. Surgery for treatment of
      the index patient was chosen by only 6%, and radioiodine by 3%. The number of
      responses was too limited to attempt any characterization of the two latter
      modalities.

PMID- 1360023
TI  - Adverse Reactions to Foods in Infancy and Childhood. Symposium proceedings.
      Madrid, Spain, April 1-3, 1992.

PMID- 1360024
TI  - Proceedings of the 12th Symposium on Medicinal Chemistry. Okayama, December 5-6,
      1991.

PMID- 1360022
TI  - Memory and naive CD4+ lymphocytes in multiple sclerosis.
AB  - Helper-inducer (CD29+CD4+) and suppressor-inducer (CD45RACD4+) T-cells have been
      recently renamed as memory and naive T-cells, respectively. We measured cells
      expressing these phenotypes in peripheral blood of 46 definite multiple sclerosis
      (MS) patients [32 relapsing-remitting (RR-MS), 14 secondary progressive (P-MS)]
      and controls. CD25+ (interleukin-2-receptor-positive) cells were also evaluated
      in the same groups of patients. RR-MS patients showed increased levels of
      CD29+CD4+ and CD25+ cells compared with controls. This finding was more evident
      in RR-MS patients during the attack than during the stable phase of the disease.
      In P-MS patients we found a reduction of CD45+CD4+ cells compared with either RR
      MS patients or control subjects. Our results show that RR-MS and P-MS are
      characterized by two different T-cell subpopulations. This finding supports the
      hypothesis that during the evolution from RR-MS and P-MS changes occur in the
      immunological status of the patients.

PMID- 1360026
TI  - Novel piperidine sigma receptor ligands as potential antipsychotic drugs.
AB  - sigma receptor ligands represent a new class of potential antipsychotic drugs.
      This paper presents the structure-activity relationships leading to novel
      disubstituted piperidine sigma ligands, which have little or no affinity for
      dopamine D2 receptors. Selectivity for sigma sites over dopamine D2 or serotonin
      5-HT2 receptors appears to be governed by the chemical nature of the piperidine
      nitrogen substituent, its distance from the basic nitrogen, and its orientation
      relative to the other piperidine substituent. Several of these compounds have
      good oral potency in some animal models used to evaluate potential antipsychotic
      drugs. The N-cyclopropylmethyl ketones and ethers (e.g. 6i (DuP 734), 6q, 18a,
      and 18n) have the best in vivo potency. Compounds 6i (DuP 734) and 6q did not
      cause catalepsy in the rat, even at very high doses. On the basis of the
      pharmacology profiles of these sigma ligands, we propose these compounds may be
      effective antipsychotic drugs, which do not induce extrapyramidal side effects or
      tardive dyskinesia.

PMID- 1360025
TI  - Effect of modification of the basic residues of dynorphin A-(1-13) amide on kappa
      opioid receptor selectivity and opioid activity.
AB  - A series of dynorphin A-(1-13) amide (Dyn A-(1-13)NH2) analogues containing
      lysine or N epsilon-acetyllysine (Lys(Ac)) was prepared by solid-phase peptide
      synthesis and evaluated for opioid receptor affinity in radioligand binding
      assays and for opioid activity in the guinea pig ileum (GPI). Substitutions were
      made at positions 6, 7, 9, 11, and 13, the basic amino acids in the C-terminus of
      the peptide, in order to assess the individual contributions of these residues to
      the kappa opioid receptor affinity and selectivity of Dyn A-(1-13)NH2. While
      substitutions of Lys(Ac) for Arg in position 6 did not affect kappa receptor
      affinity, it enhanced affinity for mu and delta receptors and therefore caused a
      loss of kappa receptor selectivity. When Lys(Ac) was substituted for Arg9, kappa
      opioid receptor affinity was enhanced and kappa receptor selectivity was
      retained. Replacement for Arg7, Lys11, or Lys13 by Lys(Ac) resulted in both
      decreased affinity and selectivity for kappa receptors. These results demonstrate
      the importance of Arg6 to the receptor selectivity profile of Dyn A-(1-13)NH2 and
      indicate that, of the five basic residues in the C-terminus, only Arg9 can be
      replaced by a nonbasic residue without substantial loss of kappa opioid receptor
      selectivity.

PMID- 1360028
TI  - Crystallization and preliminary crystallographic analysis of aspartate-beta
      semialdehyde dehydrogenase from Escherichia coli.
AB  - Aspartate-beta-semialdehyde dehydrogenase catalyzes the NADPH-mediated reductive
      dephosphorylation of beta-aspartylphosphate at a branch point in the biosynthesis
      of several amino acids. The enzyme from Escherichia coli has been crystallized by
      the vapor diffusion method from Tris buffer (pH 8.5) using polyethylene glycol
      4000 as a precipitant. The crystals are orthorhombic and have the symmetry of
      space group P222(1), with unit cell dimensions of a = 177.8 A, b = 59.9 A, c =
      118.65 A, and alpha = beta = gamma = 90 degrees. The dimensions and space group
      are indicative of two enzyme dimers (40 kDa per subunit) in the asymmetric unit.
      The crystals show strong diffraction, and a native data set has been collected to
      2.5 A resolution.

PMID- 1360027
TI  - Synthesis and pharmacological characterization of 2-(4-chloro-3
      hydroxyphenyl)ethylamine and N,N-dialkyl derivatives as dopamine receptor
      ligands.
AB  - 2-(4-Chloro-3-hydroxyphenyl)ethylamine (4) and some derivatives were synthesized
      as dopamine (DA) receptor ligands. Amine 4 retains the dopaminergic pharmacophore
      2-(3-hydroxyphenyl)-ethylamine, and the chlorine atom replaces the "para"
      hydroxyl group of DA. The derivatives 18a-e were obtained by introducing on the
      nitrogen of amine 4 the n-propyl and 2-phenylethyl or 3-phenylpropyl groups which
      can be accommodated by the D-2 receptor lipophilic sites 3C and pi 3,
      respectively. The affinity and selectivity of these compounds for D-1 and D-2
      subtypes was determined in radioligand competition assays for the DA receptors of
      rat striatum membranes using [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2
      selective) as radioligands. The amine 4 shows about 7-fold lower affinity than DA
      for both sites and is not able to discriminate between the two subtypes of DA
      receptors. The introduction of two n-propyl groups (18a) on the nitrogen atom
      reduces by one-half and doubles the affinity for D-1 and D-2 binding sites,
      respectively. The substitution of an n-propyl group with different alkylphenyl
      groups, to give compounds 18b-e, increases the affinity for the D-2 subtype from
      19-fold to 36-fold. These compounds have the same affinity at the D-2 site as the
      DA agonist N-n-propyl-N-(2-phenylethyl)-2-(3-hydroxyphenyl)-ethylamine (2a) and
      are about 20 times more selective than DA for this binding site. In the assay for
      D-2 receptor mediated inhibition of adenylate cyclase activity, all the tested
      compounds behaved as D-2 agonists; N-n-propyl-N-[2(4-hydroxyphenyl)ethyl]- (18d)
      and N-n-propyl-N-(2-phenyl-ethyl)-2-(4-chloro-3-hydroxyphenyl)ethylamine (18b)
      were more effective than DA or 2a. On the other hand, all compounds were less
      effective than DA in stimulation of adenylate cyclase activity in rat striatal
      homogenates, a kind of effect which is mediated by the D-1 subtype of DA
      receptors. These results suggest that the nitrogen substitution enhances the
      affinity and selectivity for the D-2 receptor. In the adenylate cyclase assay,
      the compounds behave as potent D-2 agonists.

PMID- 1360030
TI  - [Necessity and limitations of effectiveness of oral beta-stimulants, theophylline
      and oral antiallergic drugs in asthma treatment].
AB  - Oral beta-stimulants, theophylline and oral antiallergic drugs are frequently
      used for asthma treatment in Japan. However, inhaled beta-stimulants and inhaled
      steroids are becoming the first and second choice of drugs in asthma treatment in
      European countries, and these three categories of drugs are becoming third or
      fourth-line therapeutic choices. Accordingly, we investigated the effectiveness
      of these drugs, which is limited by their pharmacological actions and effects. As
      found in this study many cases of bronchial asthma cannot be well controlled by
      their agents, either alone or in combination. The necessity of these drugs for
      the treatment of chronic bronchial asthma was investigated. Substitution of
      inhaled beta-stimulant for oral beta-stimulant was possible in 8 of 15 cases.
      However, in 7 cases, substitution was impossible because of the patient's
      complaints, and it could not be concluded that oral beta-stimulants are necessary
      for asthma treatment. Theophylline was substituted by inhaled corticosteroids in
      6 of 8 cases. Oral antiallergic drugs were substituted by inhaled corticosteroids
      in 5 of 6 cases. These results do not conclusively indicate that theophylline and
      oral antiallergic drugs are not necessary for asthma treatment.

PMID- 1360029
TI  - [Flow cytometric techniques for measurement of proliferating cell nuclear antigen
      (PCNA)].
AB  - Flow cytometric techniques have been developed for measurement of proliferating
      cell nuclear antigen (PCNA), which allows studies on the proliferative capacity
      of cells and tissues. PCNA-DNA dual staining procedures, for both fixed and
      unfixed cells, and analytical method by FCM are presented. We recommend
      performing either the fixed or unfixed method. Our studies using the MCF7 human
      breast adenocarcinoma cell line and the A549 human lung squamous cell carcinoma
      cell line, in the exponential growth phase, revealed that both ethanol and
      acetone were satisfactory fixatives, in contrast to methanol and
      paraformaldehyde, and PI with a concentration of 25 micrograms/ml was most
      suitable compared with 50 and 100 micrograms/ml.

PMID- 1360031
TI  - [Assessment and management of acute severe asthma].
AB  - In the management of acute severe asthma it is very important to start the
      treatment as soon as possible, by appropriate evaluation of the physical status
      and signs of airflow obstruction. We propose a guideline to be used by patients
      with asthma, emergency car crews, physicians and nurses to evaluate the severity
      and to choose the appropriate management of acute asthma, including intubation
      and mechanical ventilation, by the assessment of clinical features, as well as
      blood gas analysis and pulmonary function test. Several researchers have
      demonstrated that the additional administration of aminophylline to inhaled or
      subcutaneous beta 2-agonist bronchodilator during the first 4 hours of an attack
      provides no additional benefit compared to the administration of beta 2-agonist
      alone. In our retrospective study of 68 episodes of acute severe asthma in the
      last 5 years at our institute, however, the additional administration of
      aminophylline with beta 2-agonists was clearly shown to be effective with
      infrequent minor side effects.

PMID- 1360032
TI  - Randomised controlled trial of Doppler ultrasound screening of placental
      perfusion during pregnancy.
AB  - We have done a randomised controlled trial to assess the effect on primary
      management and outcome of routine doppler ultrasound examinations of the
      umbilical and uterine arteries during pregnancy. Over 9 months, 2600 women with
      singleton pregnancies were recruited from a general obstetric population. Of 2475
      women who delivered in hospital after 20 weeks' gestation, 1246 had been
      allocated at random to receive standard antenatal care with routine doppler
      examinations. The first doppler ultrasound was done at 19-22 weeks' gestation,
      and thereafter examinations were monthly if the pregnancy was considered high
      risk (192) or once at 32 weeks if considered low risk (1054). The control group
      of 1229 women received standard, antenatal care without doppler ultrasonography.
      The study groups did not differ in number of antenatal admissions or
      cardiotocographs, gestational age at delivery, method of delivery, frequency of
      deliveries with fetal distress, or need for resuscitation or admission to the
      neonatal intensive care unit. More perinatal deaths occurred in the doppler group
      (17 vs 7, relative risk 2.4, 95% Cl 1.00-5.76), but only 1 of 11 normally formed
      stillbirths and none of the 4 normally formed neonatal deaths after 24 weeks'
      gestation had an abnormal umbilical-artery doppler examination. We did not
      demonstrate any improvement in neonatal outcome by routine doppler ultrasound
      screening of a general obstetric population.

PMID- 1360033
TI  - Antinuclear autoantibodies in women with silicone breast implants.
AB  - Clinical syndromes resembling autoimmune diseases have been reported in women who
      have had breast augmentation procedures. To see whether there is a humoral immune
      response in these diseases that is similar to the immune response in their
      idiopathic counterparts, we assessed the immunological specificity of antinuclear
      antibodies (ANAs) and certain epidemiological features in 24 patients, all of
      whom (with 1 exception) had received silicone gel breast implants. ANA
      specificities were identified by indirect immunofluorescence, immunodiffusion,
      western blot analysis, and immunoprecipitation of radiolabelled intracellular
      proteins. Of 11 patients who had symptoms and signs that met criteria for defined
      autoimmune diseases, 7 had scleroderma or subsets of this disorder and the others
      had systemic lupus erythematosus, rheumatoid arthritis, or overlapping autoimmune
      diseases. High ANA titres were present in 10 of these 11 patients and the ANA
      specificities were similar to those found in the idiopathic forms of the
      corresponding autoimmune diseases. Trauma, with resultant rupture of implants,
      accelerated onset of symptoms. 13 other patients had autoimmune disorders of a
      less clearly defined nature and low titres of ANAs whose specificities could not
      be identified. ANAs are associated with the development of autoimmune
      complications in women with silicone breast implants. Further studies are needed
      to see whether this relation is one of cause and effect and whether ANAs might be
      early serological markers preceding development of autoimmune symptoms.

PMID- 1360034
TI  - Effects of dual-chamber pacing with short atrioventricular delay in dilated
      cardiomyopathy.
AB  - Mitral or tricuspid regurgitation of long duration may so shorten the ventricular
      filling time in dilated cardiomyopathy that stroke volume is limited. We assessed
      the effects of changing the atrioventricular interval during temporary or
      permanent dual-chamber DDD pacing in twelve dilated cardiomyopathy patients with
      short ventricular filling times due to regurgitation. We measured ventricular
      filling time and cardiac output with doppler echocardiography and exercise
      capacity on a treadmill, at baseline and with the best atrioventricular delay
      during pacing. The durations of both mitral and tricuspid regurgitation were
      significantly shorter at the shorter atrioventricular interval (mean reductions
      85 [95% CI 60-110] ms and 110 [75-150] ms, respectively; p < 0.001 for both).
      There were consequent increases in left-ventricular and right-ventricular filling
      times (65 [35-95] ms and 90 [60-120] ms, p < 0.001). For each 50 ms reduction in
      atrioventricular delay, left-ventricular filling time increased by 35 ms in six
      subjects with presystolic mitral regurgitation and right-ventricular filling time
      by 30 ms in nine subjects with presystolic tricuspid regurgitation. At the short
      atrioventricular interval, cardiac output was greater than baseline (by 1.1 [0.8
      1.4] l/min, p < 0.01) and there were rises in exercise duration (104 [45-165] s,
      p < 0.05) and maximum oxygen consumption (2.1 [1.5-2.7] ml kg-1 min-1, p < 0.05).
      There was a decrease in the Likert visual analogue score of breathlessness at
      peak exercise (8.6 [SD 2.1] vs 4.9 [3.1], p < 0.01). Although from a small
      sample, these findings suggest that DDD pacing with a short atrioventricular
      delay may have therapeutic potential in patients with dilated cardiomyopathy,
      even in the absence of conventional indications for pacemaker implantation.

PMID- 1360035
TI  - High frequency of antibodies to Mycoplasma penetrans in HIV-infected patients.
AB  - Mycoplasma penetrans, a novel mycoplasma isolated from HIV-1-infected patients
      with AIDS, has pathogenic properties associated with in-vivo virulence. Enzyme
      linked immunosorbent assay and western blotting detected a more than 100 times
      higher frequency of antibodies to the mycoplasma in serum from HIV-1-infected
      patients with AIDS (40%) than from HIV-negative controls (0.3%). Serum from 20%
      of HIV-1-infected, symptom-free individuals also had M penetrans specific
      antibodies. The antibodies' major immunoreactivity was directed against P35 and
      P38, the two main lipid-associated membrane protein antigens of the organism.
      Patients attending sexually transmitted disease clinics had a low frequency of
      antibody (0.9%). None of 178 HIV-negative patients with different non-AIDS
      diseases, many associated with immune dysfunction and/or low white cell counts,
      tested positive for the antibodies. M penetrans, apparently not a commensal and
      not a simple opportunist, is uniquely associated with HIV-1 infection and AIDS.

PMID- 1360036
TI  - Nonsense mutation of glucokinase gene in late-onset non-insulin-dependent
      diabetes mellitus.
AB  - A nonsense mutation at codon 186 in exon 5 of the gene for glucokinase, an enzyme
      important for glucose-induced insulin secretion, was identified in a Japanese
      patient with late-onset non-insulin-dependent diabetes mellitus (NIDDM). All
      affected members of her family were heterozygous for the mutation and had late
      onset NIDDM or impaired glucose tolerance, whereas unaffected members showed
      normal glucose tolerance. The early insulin response to oral glucose was impaired
      in affected relatives, but was normal in those unaffected. These findings suggest
      that the glucokinase mutation raises the set-point of pancreatic beta cells for
      glucose-induced insulin secretion, leading to abnormal glucose tolerance in some
      patients with late-onset NIDDM.

PMID- 1360037
TI  - Insemination of HIV-negative women with processed semen of HIV-positive partners.
AB  - Many HIV-discordant couples want to have children so much that they are willing
      to abandon condom-protected sexual intercourse irrespective of the risks.
      Previous testing in our laboratory showed that gradient centrifugation followed
      by a swim-up procedure effectively removed HIV-1-infected cells from the semen of
      HIV-seropositive men. 85 HIV-discordant couples were screened for fertility; 29
      women were found suitable for a timed insemination course with the processed
      semen of their HIV-seropositive partner. None of the inseminated women
      seroconverted, and 17 pregnancies were achieved in 15 women. All 10 babies born
      to these mothers remain HIV seronegative. The findings may help in the
      counselling of such couples and also give them hope of having healthy babies.

PMID- 1360038
TI  - Inherited idiopathic dilated cardiomyopathy with multiple deletions of
      mitochondrial DNA.
AB  - Idiopathic dilated cardiomyopathy (DCM) is often familial, but the pathogenetic
      mechanisms of DCM are unknown. We report a woman and her son who both died of
      DCM. The son's cardiac and skeletal muscles showed a high proportion of
      mitochondrial DNA (mtDNA) with multiple large deletions by Southern-blot
      hybridisation and polymerase chain reaction analyses. Amplification of the
      mother's cardiac mtDNA from 20-year-old paraffin-embedded sections showed that
      she also had deletions of mtDNA. These data suggest that a subgroup of inherited
      DCMs is associated with mtDNA mutations.

PMID- 1360039
TI  - Advance directives.

PMID- 1360040
TI  - Guinea worm: good news from Ghana.

PMID- 1360041
TI  - Endotoxaemia or endotoxinaemia?

PMID- 1360042
TI  - Apartheid and health: is reform merely cosmetic?

PMID- 1360043
TI  - Glue ear guidelines: time to act on the evidence.

PMID- 1360044
TI  - Creatinine clearance during cimetidine administration for measurement of
      glomerular filtration rate.
AB  - Creatinine clearance inaccurately estimates true glomerular filtration rate (GFR)
      because of tubular secretion of creatinine. We studied the ability of oral
      cimetidine, a blocker of tubular creatinine secretion, to improve the accuracy of
      measuring creatinine clearance. Clearances of inulin and endogenous creatinine
      were simultaneously measured in 16 patients with renal disease before
      administration of cimetidine and during 8 successive 3 h clearance periods with
      cimetidine 400 mg as priming dose followed by 200 mg every 3 h. At baseline,
      creatinine relative to inulin clearance (ClC/Cll) ranged from 1.14 to 2.27. With
      cimetidine, ClC/Cll approached unity in 8 patients (mean 1.02 [SD 0.03]), but
      considerably exceeded unity in 8 others (1.33 [0.14]). Plasma
      cimetidine/creatinine ratio was smaller in this second group, due to
      significantly higher renal clearance of cimetidine (333 [136] vs 165 [89] ml/min,
      p = 0.01). In a further study, cimetidine dose and, consequently plasma
      cimetidine concentration, was increased in 6 additional patients who had
      incomplete inhibited previously. This increased dose completely inhibited tubular
      creatinine secretion in the third until the sixth hour, so that creatinine
      clearance equalled GFR. Provided an adequate dose of cimetidine is given, 24 h
      creatinine clearance during administration of drug measures GFR accurately in
      patients with renal disease. However, because of the maximum daily dose of
      cimetidine that is advised, short clearance times (3 h) are recommended.

PMID- 1360045
TI  - Phenotype and genotype heterogeneity in autosomal dominant polycystic kidney
      disease.
AB  - It is now clear that mutations of at least two genetic loci can lead to autosomal
      dominant polycystic kidney disease (ADPKD). We have compared the clinical
      features of ADPKD caused by mutations at the PKD1 locus (linked to the alpha
      globin complex on chromosome 16) with those of disease not linked to the locus
      (non-PKD1). We identified 18 families (285 affected members) with mutations at
      PKD1 and 5 families (49 affected individuals) in which involvement of this locus
      could be dismissed. Non-PKD1 patients lived longer than PKD1 patients (median
      survival 71.5 vs 56.0 years), had a lower risk of progressing to renal failure
      (odds ratio 0.35, 95% CI 0.13-0.92), were less likely to have hypertension (odds
      ratio adjusted for age and family of origin 0.29, 0.11-0.80), were diagnosed at
      an older age (median 69.1 vs 44.8 years), and had fewer renal cysts at the time
      of diagnosis. Although most of the PKD1 families were ascertained through clinics
      treating patients with renal impairment, no non-PKD1 family was identified
      through this source. Non-PKD1 ADPKD has a much milder phenotype than that linked
      to PKD1. Partly as a result of this difference in severity, the reported
      prevalence of this genotype is probably an underestimate.

PMID- 1360046
TI  - Medical barriers to access to family planning.

PMID- 1360047
TI  - Canada: blood self-sufficiency.

PMID- 1360048
TI  - Mercy without certainty.

PMID- 1360049
TI  - Didanosine for zidovudine-intolerant patients with HIV disease.

PMID- 1360050
TI  - A1B8DR3-associated CD8-positive T-cell expansion in HIV infection.

PMID- 1360051
TI  - Beneficial effects of intravenous immunoglobulins in AIDS.

PMID- 1360052
TI  - Role of glucose and insulin resistance in development of type 2 diabetes
      mellitus.

PMID- 1360053
TI  - Role of glucose and insulin resistance in development of type 2 diabetes
      mellitus.

PMID- 1360054
TI  - Cardiotocography and Doppler velocimetry for surveillance of small-for
      gestational-age fetuses.

PMID- 1360055
TI  - Cardiotocography with ST-waveform analysis for fetal monitoring.

PMID- 1360056
TI  - Adjuvant treatment with 5-fluorouracil for colorectal cancer.

PMID- 1360057
TI  - Apolipoprotein epsilon 4 and coronary artery disease.

PMID- 1360058
TI  - Serum cholesterol, triglycerides, and aggression.

PMID- 1360059
TI  - Serum cholesterol, triglycerides, and aggression.

PMID- 1360060
TI  - Serum cholesterol, triglycerides, and aggression.

PMID- 1360061
TI  - Apolipoprotein epsilon 4 and coronary artery disease.

PMID- 1360062
TI  - Apolipoprotein epsilon 4 and coronary artery disease.

PMID- 1360063
TI  - Hypertonic saline solution for wound dressing.

PMID- 1360064
TI  - Virus-induced apnoea and theophylline.

PMID- 1360065
TI  - Biliary drug lithiasis: dipyridamole gallstones.

PMID- 1360066
TI  - Dental prophylaxis for endocarditis.

PMID- 1360068
TI  - Living kidney donors.

PMID- 1360067
TI  - Misconceptions on nutrition of refugees.

PMID- 1360069
TI  - Specialist medical training and the European community.

PMID- 1360070
TI  - Drug safety monitoring in Europe.

PMID- 1360071
TI  - Antismoking adverts and sports sponsorship.

PMID- 1360072
TI  - Methods for increased poliovirus diagnosis.

PMID- 1360073
TI  - Increase in birthweight in undernourished women.

PMID- 1360074
TI  - Increase in birthweight in undernourished women.

PMID- 1360075
TI  - Increase in birthweight in undernourished women.

PMID- 1360076
TI  - Slaked lime and betel nut cancer in Papua New Guinea.

PMID- 1360077
TI  - Proton irradiation for hepatocellular carcinoma.

PMID- 1360078
TI  - Vitamin A supplementation and childhood mortality.

PMID- 1360079
TI  - Randomised trial of case finding and surveillance of elderly people at home.

PMID- 1360080
TI  - Congenital complete heart block in children of mothers with primary Sjogren's
      syndrome.

PMID- 1360081
TI  - Rapid misdiagnosis by Mycobacterium avium-intracellulare masquerading as
      tuberculosis in PCR/DNA probe tests.

PMID- 1360082
TI  - Immunotherapy for drug-resistant tuberculosis.

PMID- 1360083
TI  - Abnormal chromosome complement after normal amniocentesis result.

PMID- 1360084
TI  - Possible role for COMT in psychosis associated with velo-cardio-facial syndrome.

PMID- 1360085
TI  - Familial defective apolipoprotein B-100: mild hypercholesterolaemia without
      atherosclerosis in a homozygous patient.

PMID- 1360086
TI  - Is splenectomy another indication for Haemophilus influenzae type b vaccination?

PMID- 1360087
TI  - Early versus delayed neonatal administration of a synthetic surfactant--the
      judgment of OSIRIS. The OSIRIS Collaborative Group (open study of infants at high
      risk of or with respiratory insufficiency--the role of surfactant.
AB  - Although exogenous surfactants are of known efficacy in the prevention and
      treatment of respiratory distress syndrome (RDS), questions remain about the best
      regimens. During 1990-91, 6774 babies were recruited to an international
      multicentre trial to assess when administration of Exosurf, a synthetic
      surfactant, should be started and how often it should be given. The clinical
      outcome is known for 6757 (99.7%) infants. 2690 babies, judged to be at high risk
      of RDS when less than 2 hours of age, were randomly allocated to either early
      administration or delayed selective administration; 96% versus 73% received
      surfactant, at median ages of 118 and 182 min. The risk of death or dependence on
      extra oxygen at the expected date of delivery was 16% (95% CI 25% to 7%) lower
      among infants allocated early administration. Early administration was also
      associated with a 32% lower risk of pneumothorax. These 2690 infants were further
      randomised in a factorial design to either two doses of surfactant 12 hours
      apart, or the option of third and fourth doses at 12-36 hour intervals if signs
      of RDS persisted or recurred. 4067 other infants who later developed RDS were
      also recruited to this comparison, giving a total of 3376 infants allocated up-to
      four doses (of whom, 45% received more than two) and 3381 allocated two doses.
      The outcome was similar in the two groups in respect of death, long-term oxygen
      dependence, and other major morbidity, even in secondary analyses restricted to
      infants who met the criteria for additional administration. There were more
      reports of poorly tolerated administration in the up-to-four doses group but no
      clear increase in serious morbidity, such as pulmonary haemorrhage. The OSIRIS
      trial suggests that early administration of surfactant to an estimated 32 babies,
      when compared with treatment of established RDS, would prevent 1 baby from dying
      and another from being dependent on extra oxygen long-term, but would entail the
      additional use of surfactant in 8 of these babies. It provides no evidence that a
      regimen including the option of third and fourth doses when signs of RDS persist
      or recur is clinically superior to a regimen of two doses.

PMID- 1360088
TI  - Prognostic significance of cytoplasmic p53 oncoprotein in colorectal
      adenocarcinoma.
AB  - Mutation of p53, a tumour-suppressor protein, leads to overexpression of the
      protein and loss of its tumour-suppressive properties. In some tumours (eg,
      breast) p53 expression is related to well-known prognostic factors, but findings
      in colorectal tumours are equivocal. We have used the polyclonal antibody CM1 to
      investigate nuclear and cytoplasmic p53 expression in colorectal tumours and to
      assess their relations with prognosis. Of 293 colorectal adenocarcinomas, 71
      (24%) showed p53 expression in the nucleus alone, 30 (10%) showed p53 in the
      cytoplasm alone, and 43 (15%) showed both nuclear and cytoplasmic expression.
      Nuclear p53 expression showed no relation with survival or Dukes' stage of the
      tumour. However, the frequency of cytoplasmic expression increased with advancing
      Dukes' stage (chi 2 for trend 11.18, 1 df, p = 0.0008) and cytoplasmic expression
      was associated with poor survival (rate ratio 2.3 [95% CI 1.6-3.3], p < 0.0001).
      Among tumours of Dukes' stage A-C, cytoplasmic expression showed prognostic value
      independent of nuclear staining, grade of differentiation, and Dukes' stage (2.3
      [1.4-3.7], p = 0.0021). We conclude that cytoplasmic expression of p53 may be a
      useful biological indicator of prognosis in colorectal adenocarcinoma.

PMID- 1360089
TI  - Effect of extended cold ischaemia with UW solution on graft function after liver
      transplantation.
AB  - Studies in animals on the use of UW solution in liver transplantation have shown
      an inverse relation between cold ischaemia time (CIT) and graft function. There
      are few clinical data on this relation in human beings. We have investigated the
      effect of extended cold ischaemia in a prospective study. We assessed early graft
      function and subsequent outcome for 306 consecutive elective liver
      transplantations; for analyses, grafts were grouped according to CIT (< 12 h
      group A, > or = 12 h group B), since a preliminary study identified 12 h as a
      significant cut-off point. Initial graft function was better in group A than
      group B, as shown by maximum alanine aminotransferase activity (mean 623 [805] vs
      946 [1148], p = 0.02), bile production on days 1-3 (p < 0.05), maximum serum
      bilirubin by day 10 (206 [166] vs 244 [163] mumol/l, p = 0.04), and frequencies
      of primary non-function (1 [0.4%] vs 4 [7%], p = 0.006) and hepatocyte necrosis
      on routine biopsy sample after reperfusion (18% vs 31%, p = 0.04). Long-term
      outcome was also better in group A than group B; graft and patient survival rates
      were higher and fewer retransplantations were needed. These findings suggest that
      cold ischaemia in UW solution for longer than 12 h is a risk factor for graft
      function and patient survival. We recommend that the limit of the safe CIT be
      reconsidered.

PMID- 1360091
TI  - Meningococcal septicaemia in a C6-deficient patient and effects of plasma
      transfusion on lipopolysaccharide release.
AB  - Patients whose blood is deficient in the terminal component of complement have an
      increased susceptibility to meningococcal infection. However, mortality from
      meningococcal infection is lower in these patients than in immunocompetent
      subjects. We studied a C6-deficient patient with meningococcal sepsis who
      received fresh frozen plasma (FFP). The patient's initial plasma endotoxin, C6,
      and terminal-complement-complex concentrations were low, but rose sharply after
      treatment with FFP. Samples of the patient's serum taken shortly after admission
      did not cause endotoxin release from Escherichia coli J5 in vitro, but endotoxin
      releasing activity was restored in serum samples taken after infusion of FFP. It
      is possible that C6-deficient patients have reduced mortality from meningococcal
      infection because their serum cannot cause acute release of endotoxin from the
      invading organism and extensive tissue damage is thus avoided.

PMID- 1360090
TI  - Diabetes mellitus associated with a pathogenic point mutation in mitochondrial
      DNA.
AB  - Family studies of diabetes mellitus (DM) show that patients are more likely to
      have affected mothers than affected fathers. Since the inheritance of
      mitochondrial (mtDNA), unlike nuclear DNA, is exclusively maternal, could it be
      that defect(s) in mtDNA account for some cases of DM? Such defects have been
      associated with rare neurological syndromes, in some of which DM has been an
      accompanying feature. We have looked for glucose intolerance and for a previously
      known point mutation of mtDNA in a family, some of whose members have a
      multisystem disorder with DM but not neurological involvement. DNA samples were
      obtained from fourteen family members. The point mutation (affecting position
      3243 in the tRNA leucine mitochondrial gene) was found in all three diabetic
      patients and post mortem tissues in the proband; it was also found in seven
      offspring of female patients. It was not found in the two children of the male
      proband. The contribution of this mutation to DM in general is not known but
      clinicians ought to be aware of the possibility, especially in families with
      multisystem disease and maternal transmission.

PMID- 1360093
TI  - Skeletal muscle in heart failure.

PMID- 1360092
TI  - Haemoglobin in gut lavage fluid as a measure of gastrointestinal blood loss.
AB  - To detect and measure occult gastrointestinal bleeding, we have measured
      haemoglobin concentrations (by HemoQuant) in the clear fluid obtained after whole
      gut lavage. In subjects with healthy gastrointestinal tracts, lavage-fluid
      haemoglobin concentrations were 0.5-5.1 mg/L, equivalent to daily blood loss of
      0.1-1.1 mL. High concentrations were found for patients with colorectal cancer,
      severe diverticular disease, and rectal varices, in seven of sixteen patients
      with active inflammatory bowel disease, and in four patients with iron-deficiency
      anaemia thought to be due to gastrointestinal bleeding. In these four patients,
      estimated blood loss ranged from 2.6-24.5 mL per day. This method could have
      various research and clinical applications.

PMID- 1360094
TI  - Steroids in acute severe asthma.

PMID- 1360096
TI  - Desferrioxamine and cerebral malaria.

PMID- 1360095
TI  - Home cholesterol testing.

PMID- 1360097
TI  - Surfactant for babies.

PMID- 1360098
TI  - Usefulness of consensus conferences: the case of albumin.
AB  - The usefulness of consensus conferences has been questioned. We have assessed the
      impact of a 1989 consensus conference about the treatment of hypovolaemia on
      prescribing practice at our hospital. Data available from the blood bank enabled
      us to follow albumin use and costs by department between 1987 and 1991. Medical
      journals, direct mail, and meetings were used to disseminate the recommendations
      of the consensus conference, which were that the only indications for albumin are
      massive haemorrhage, plasmapheresis, massive hypoalbuminaemia, and volume
      expansion in pregnancy; for hypovolaemia caused by septic shock or vasoplegia,
      fluid gelatins and crystalloids should be used. In the year after the conference,
      and in subsequent years, albumin use and costs were 40% lower than before the
      conference, even though total medical expenditure continued to rise and numbers
      of patients admitted did not change. We believe that consensus conferences can be
      a useful means of improving medical practice. The features that ensured success
      in this programme were the small number of prescribers, the homogeneous setting,
      and the frequent restatement of the recommendations.

PMID- 1360099
TI  - Geographic distribution of physicians in Japan.
AB  - In the 1970s, Japan's physician manpower policy was to increase the number of
      medical students and medical schools to ease the difficulties caused by shortage
      of doctors and their maldistribution. 34 medical schools were established during
      this time, which eventually doubled the number of newly certificated physicians
      from about 4000 to about 8000 per year by the mid 1980s. To examine the success
      of this policy, we analysed the numbers of physicians in relation to the
      population in all municipal bodies (n = 3268) in Japan. Between 1980 and 1990,
      the number of practising physicians increased by about 37%, and the ratio of
      physicians per 100,000 population increased from 127 to 165 throughout the
      country. However, analyses by the Lorenz curve and the Gini coefficient indicated
      that the inequality in physician distribution did not improve. While municipal
      bodies with a population over 30,000 gained proportionally more physicians, most
      communities with fewer than 10,000 residents showed little gain. Our findings
      have important implications for policy changes now being considered by the
      government to plan the future supply of physician manpower in Japan. A policy
      that will alleviate physician maldistribution also needs to be devised.

PMID- 1360100
TI  - Malignant melanoma excision margins: making a choice.

PMID- 1360101
TI  - WHO clofibrate/cholesterol trial: clarifications.

PMID- 1360102
TI  - Breastfeeding and antibody responses to routine vaccination in infants.

PMID- 1360103
TI  - Bartter's syndrome and growth hormone replacement.

PMID- 1360104
TI  - Muscling in on salbutamol.

PMID- 1360105
TI  - Muscling in on salbutamol.

PMID- 1360106
TI  - Spurious euglycaemia in severe diabetic ketoacidosis.

PMID- 1360107
TI  - Umbilical cord blood progenitor cells for clinical transplantation.

PMID- 1360108
TI  - Chemicals and human cancer.

PMID- 1360109
TI  - Smoking and decreased fertilisation rates in vitro.

PMID- 1360110
TI  - Ondansetron and chest pain.

PMID- 1360111
TI  - Painful hypertrophic scarring and neuropeptides.

PMID- 1360112
TI  - Visual loss associated with bromocriptine.

PMID- 1360113
TI  - Erythropoietin production and pH.

PMID- 1360114
TI  - Living-related liver transplantation in fulminant hepatic failure.

PMID- 1360115
TI  - Transmission of HIV-associated tuberculosis to health-care workers.

PMID- 1360116
TI  - Spurious malarial antibodies in HIV infection.

PMID- 1360117
TI  - Neuronal loss in symptom-free HIV infection.

PMID- 1360118
TI  - Changing case-definition for AIDS.

PMID- 1360120
TI  - Distinction awards and Cochrane.

PMID- 1360119
TI  - Changing case-definition for AIDS.

PMID- 1360122
TI  - EC medicines agency.

PMID- 1360121
TI  - Prohibition of alcohol in India.

PMID- 1360123
TI  - Health care in developing countries.

PMID- 1360124
TI  - Prohibition of alcohol in India.

PMID- 1360126
TI  - Understanding the low uptake of presymptomatic DNA testing for Huntington's
      disease.

PMID- 1360125
TI  - Varicella and acyclovir.

PMID- 1360127
TI  - Zinc status in breastfed infants.

PMID- 1360128
TI  - Zinc status in breastfed infants.

PMID- 1360129
TI  - Human papillomavirus DNA in urine of women with preneoplastic and neoplastic
      cervical lesions.

PMID- 1360130
TI  - Pneumococcal immunisation and the healthy elderly.

PMID- 1360131
TI  - Patient guidance after 131I therapy.

PMID- 1360132
TI  - Pneumococcal immunisation and the healthy elderly.

PMID- 1360133
TI  - "Pseudo-resistant" malaria in tropical countries.

PMID- 1360134
TI  - Pathophysiology of obesity.

PMID- 1360135
TI  - Screening for extended-spectrum cephalosporin resistance in pneumococci.

PMID- 1360136
TI  - In Situ Hybridization and the Liver. Symposium proceedings. Sestriere, Italy.
      April 2-4, 1992.

PMID- 1360137
TI  - Analysis of the transcriptional activity of the hut promoter in Bacillus subtilis
      and identification of a cis-acting regulatory region associated with catabolite
      repression downstream from the site of transcription.
AB  - Levels of transcripts initiated at a hut promoter in Bacillus subtilis were
      analysed. The addition of histidine to the culture medium increased the level of
      the transcript sixfold. In the presence of histidine and glucose together, the
      level of the transcript was reduced to the level in the absence of induction.
      Furthermore, addition of a mixture of 16 amino acids to cultures of induced cells
      and of catabolite-repressed cells decreased levels of the transcript 16-fold and
      2.6-fold, respectively. Thus, it appears that at least three regulatory
      mechanisms associated with induction, catabolite repression, and amino acid
      repression, control the transcriptional activity of the hut promoter. Expression
      of the hut promoter-lacZ fusions that contained various regions of the hutP gene
      and deletion analysis of the hutP region revealed a cis-acting sequence
      associated with catabolite repression that was located between positions +204 and
      +231 or around position +203.

PMID- 1360138
TI  - Mono- and bi-phasic Salmonella typhi: genetic homogeneity and distinguishing
      characteristics.
AB  - Several lines of evidence indicate a relatively low genetic heterogeneity in the
      natural Salmonella typhi population. However, some S. typhi isolates found in
      Indonesia express, instead of the usual fliC-d flagellin gene, a different
      flagellar gene fliC-j. In addition, Indonesian strains may have a second
      flagellar antigen fliC-z66. We have previously suggested, on the basis of the
      flagellar antigen constitution, that S. typhi evolved in an isolated human
      population in Indonesia. In order to test this hypothesis, we have gathered S.
      typhi isolates from around the world and tested the genetic heterogeneity among
      them. In general, polymorphism was greater in isolates from the Far East, as was
      indicated by Southern hybridizations with rDNA and fliC DNA probes. Gene fliC-j
      was not found in S. typhi isolates, other than those from Indonesia. However, the
      one-clone origin of S. typhi was indicated by a common DNA fingerprint pattern
      and by the occurrence, in the 5' end region of the fliC gene, of 10 scattered
      nucleotides that differ from the corresponding 10 nucleotides in other fliC
      alleles studied. These nucleotides were present in all isolates tested but did
      not change the amino acid sequence of the flagellin polypeptide.

PMID- 1360139
TI  - Characterization of a Bordetella pertussis fimbrial gene cluster which is located
      directly downstream of the filamentous haemagglutinin gene.
AB  - The biosynthesis of fimbriae is a complex process requiring multiple genes which
      are generally found clustered on the chromosome. In Bordetella pertussis, only
      major fimbrial subunit genes have been identified, and no evidence has yet been
      found that they are located in a fimbrial gene cluster. To locate additional
      genes involved in the biosynthesis of B. pertussis fimbriae, we used TnphoA
      mutagenesis. A PhoA+ mutant (designated B176) was isolated which was affected in
      the production of both serotype 2 and 3 fimbriae. Cloning and sequencing of the
      DNA region harbouring the transposon insertion revealed the presence of at least
      three additional fimbrial genes, designated fimB, fimC and fimD. The transposon
      was found to be located in fimD. Analysis of PhoA activity indicated that the
      fimbrial gene cluster was positively regulated by the bvg locus. A potential
      binding site for BvgA was observed upstream of fimB. FimB showed homology with
      the so-called chaperone-like fimbrial proteins, while FimC was homologous with a
      class of fimbrial proteins located in the outer membrane and presumed to be
      involved in transport and anchorage of fimbrial subunits. An insertion mutation
      in fimB abolished the expression of fimbrial subunits, implicating this gene in
      the biosynthesis of both serotype 2 and 3 fimbriae. Upstream of fimB a pseudogene
      (fimA) was observed which showed homology with the three major fimbrial subunit
      genes, fim2, fim3 and fimX. The construction of a phylogenetic tree suggested
      that fimA may be the primordial major fimbrial subunit gene from which the other
      three were derived by gene duplication. Interestingly, the fimbrial gene cluster
      was found to be located directly downstream from the gene coding for the
      filamentous haemagglutinin, an important B. pertussis adhesin, possibly
      suggesting co-operation between the two loci in the pathogenesis of pertussis.

PMID- 1360140
TI  - Cloning and characterization of fxp, the flexible pilin gene of Aeromonas
      hydrophila.
AB  - The flexible pilus of Aeromonas hydrophila is a morphologically and biochemically
      unique organelle which binds eukaryotic cell surfaces and whose expression is
      induced by specific physiochemical conditions. fxp, the structural gene coding
      for the flexible pilus subunit, was localized on a 7.6kb plasmid of A. hydrophila
      strain AH26. A putative Shine-Dalgarno sequence and -10 and -35 regions were
      identified, a signal peptide sequence delineated, and the coding sequence
      compared with other bacterial sequences and found to be unique. Plasmid and
      chromosomal DNA was prepared from 66 other Aeromonas strains and 12 strains from
      other bacterial genera and examined by Southern blot hybridization using a
      labelled fxp oligonucleotide and the 7.6kb plasmid as probes. No hybridizing
      sequences were identified except in the original strain, AH26. It is proposed
      that fxp codes for a highly evolved organelle, possibly widely distributed in
      nature, but that it is carried on a genetic element that is rapidly lost from
      most strains upon in vitro cultivation and storage.

PMID- 1360141
TI  - Heartburn--lifting the veil of mythology.

PMID- 1360142
TI  - [Immunohistochemical study of cell proliferation in breast cancer: preliminary
      report].

PMID- 1360143
TI  - Chinese hamster ovary mRNA-dependent, Na(+)-independent L-leucine transport in
      Xenopus laevis oocytes.
AB  - In freshly prepared uninjected folliculated oocytes, Na(+)-independent leucine
      uptake is mediated predominantly by a system L-like transport system. Removal of
      follicular cells, however, results in an irreversible loss of this transport
      activity. When total poly(A)+ mRNA derived from Chinese hamster ovary (CHO) cells
      was injected into prophase-arrested stage V or VI Xenopus laevis oocytes,
      enhanced expression of Na(+)-independent leucine transport was observed. The
      injected mRNAs associated with increased levels of leucine uptake were between 2
      and 3 kb in length. The newly expressed leucine transport activity exhibited
      important differences from the known characteristics of system L, which is the
      dominant Na(+)-independent leucine transporter in CHO cells as well as in freshly
      isolated folliculated oocytes. The CHO mRNA-dependent leucine uptake in oocytes
      was highly sensitive to the cationic amino acids lysine, arginine, and and
      ornithine (> 95% inhibition). As with the leucine uptake, an enhanced lysine
      uptake was also observed in size-fractionated CHO mRNA-injected oocytes. The
      uptakes of leucine and lysine were mutually inhibitable, suggesting that the
      newly expressed transporter was responsible for uptakes of both leucine and
      lysine. The inhibition of uptake of lysine by leucine was Na+ independent, thus
      clearly distinguishing it from the previously reported endogenous system y+
      activity. Furthermore, the high sensitivity to tryptophan of the CHO mRNA
      dependent leucine transport was in sharp contrast to the properties of the
      recently cloned leucine transport-associated gene from rat kidney tissue,
      although leucine transport from both sources was sensitive to cationic amino
      acids. Our results suggest that there may be a family of leucine transporters
      operative in different tissues and possibly under different conditions.

PMID- 1360144
TI  - Relative roles of signals upstream of AAUAAA and promoter proximity in regulation
      of human immunodeficiency virus type 1 mRNA 3' end formation.
AB  - At least two mechanisms have been implicated in regulating poly(A) site use in
      human immunodeficiency virus type 1 (HIV-1): inhibition of basal signals within
      500 nucleotides (nt) of the cap site, leading to specific suppression of the 5'
      poly(A) site, and stimulation of basal signals by long terminal repeat U3
      sequences, leading to specific activation of the 3' poly(A) site. We determined
      the relative contributions of these mechanisms in a HeLa cell
      transcription/processing reaction and by transient transfection analysis. In
      vitro, the efficiency of basal signals is equivalent close to (270 nt) and far
      from (1,080 nt) the promoter and is stimulated at least 30-fold in both positions
      by upstream U3 sequences. In vivo, U3 sequences also enhance processing at both
      positions. There are two additional effects when the poly(A) site is close to the
      cap site: at least a 15-fold reduction in total RNA levels and a 5-fold decrease
      in relative levels of RNA processed at the HIV-1 site in constructs containing
      U3. Both effects are overcome by insertion of upstream splicing signals in an
      orientation-dependent manner. Splicing appears to influence poly(A)+ RNA levels
      by two distinct mechanisms: stabilizing nuclear transcripts and directly
      stimulating 3' end formation. It is proposed that upstream elements play major
      roles in regulating poly(A) site choice and in controlling the subsequent fate of
      polyadenylated RNA. The impact of these findings on mechanisms of mRNA biogenesis
      in the HIV-1 provirus is discussed.

PMID- 1360146
TI  - Persistent paralysis after vecuronium administration.

PMID- 1360145
TI  - A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole as
      primary prophylaxis against Pneumocystis carinii pneumonia in patients with human
      immunodeficiency virus infection. The Dutch AIDS Treatment Group.
AB  - BACKGROUND: Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) is
      recommended for patients with human immunodeficiency virus (HIV) infection if
      their CD4 cell counts are below 200 per cubic millimeter (0.2 x 10(9) per liter).
      Either aerosolized pentamidine or trimethoprim-sulfamethoxazole (co-trimoxazole)
      is commonly prescribed for prophylaxis, but the relative efficacy and toxicity of
      these agents are unknown. METHODS: We conducted a multicenter trial involving 215
      HIV-infected patients with no history of PCP but with CD4 cell counts below 200
      per cubic millimeter. The patients were randomly assigned to one of three
      regimens: aerosolized pentamidine once a month, 480 mg of trimethoprim
      sulfamethoxazole once a day (80 mg of trimethoprim and 400 mg of
      sulfamethoxazole), or 960 mg of trimethoprim-sulfamethoxazole once a day (160 mg
      and 800 mg, respectively). The cumulative incidence of PCP was estimated by
      Kaplan-Meier survival analysis. RESULTS: After a mean follow-up of 264 days, 6 of
      the 71 patients in the pentamidine group had a confirmed first episode of PCP (11
      percent), whereas none of the 142 patients in the two trimethoprim
      sulfamethoxazole groups had PCP (P = 0.002). However, adverse events that
      required discontinuation of the medication were much more frequent in the
      trimethoprim-sulfamethoxazole groups (17 and 18 patients) than in the pentamidine
      group (2 patients). The adverse reactions occurred significantly sooner in the
      group given 960 mg of trimethoprim-sulfamethoxazole than in the group given 480
      mg (mean time, 16 vs. 57 days; P = 0.02). CONCLUSIONS: For patients with HIV
      infection, trimethoprim-sulfamethoxazole taken once a day is more effective as
      primary prophylaxis against PCP than aerosolized pentamidine administered once a
      month, although adverse drug reactions are more frequent with trimethoprim
      sulfamethoxazole.

PMID- 1360147
TI  - Persistent paralysis after vecuronium administration.

PMID- 1360148
TI  - Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160.
AB  - The envelope glycoprotein of human immunodeficiency virus (HIV) initiates
      infection by mediating fusion of the viral envelope with the cell membrane.
      Fusion activity requires proteolytic cleavage of the gp160 protein into gp120 and
      gp41 at a site containing several arginine and lysine residues. Activation at
      basic cleavage sites is observed with many membrane proteins of cellular and
      viral origin. We have recently found that the enzyme activating the
      haemagglutinin of fowl plague virus (FPV), an avian influenza virus, is furin.
      Furin, a subtilisin-like eukaryotic endoprotease, has a substrate specificity for
      the consensus amino-acid sequence Arg-X-Lys/Arg-Arg at the cleavage site. We show
      here that the glycoprotein of HIV-1, which has the same protease recognition
      motif as the FPV haemagglutinin, is also activated by furin.

PMID- 1360149
TI  - Malaria. Another route to a vaccine?

PMID- 1360150
TI  - Expression of Hox-7.1 in myoblasts inhibits terminal differentiation and induces
      cell transformation.
AB  - The terminal differentiation of myogenic cells initiates in the proximal portion
      of the limb bud whereas the distal region remains undifferentiated and
      proliferative. The apical ectodermal ridge maintains the progress zone in an
      undifferentiated state and induces proliferation of limb mesenchymal cells. Hox
      7.1, a homeobox-containing gene, is expressed throughout the limb bud when limb
      outgrowth begins, whereas transcripts are later restricted to distal limb
      mesenchyme which is the proposed site of positional specification.
      Transplantation of proximal limb bud tissue into the distal portion of the limb
      results in a re-expression of Hox-7.1 in the transplanted mesenchyme. Similar
      grafts result in a positional reassignment to distal structures as well as de
      differentiation of the grafted proximal tissue. Because of the association of Hox
      7.1 expression with proliferative and undifferentiated cells, we tested whether
      Hox-7.1 regulates differentiation by transfection of Hox-7.1 complementary DNA
      into determined myogenic cells which represent one mesenchymal lineage in the
      limb. Here we report that forced expression of Hox-7.1 blocks terminal
      differentiation and results in a corresponding decrease in steady-state levels of
      MyoD1. Consistent with the association of Hox-7.1 with proliferation, Hox-7.1
      expressing cells also acquire a transformed phenotype. Forced expression of Hox
      8.1, a related Hox-gene, does not affect terminal differentiation indicating that
      the effects of Hox-7.1 are specific.

PMID- 1360151
TI  - Effects of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline on the prolactin
      suppression induced by a series of full and partial dopamine D2 receptor agonists
      in male rats.
AB  - The effect of pretreatment with a high dose of the alkylating agent N
      ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (20 mg/kg, 24 h) on the
      intrinsic activity displayed by a series of full and partial dopamine D2 receptor
      agonists on prolactin regulating pituitary D2 receptors in male rats was studied.
      To increase baseline prolactin levels, gamma-butyrolactone in a dose inhibiting
      brain dopamine neurotransmission was given to all animals. In controls, i.e. rats
      not given EEDQ, supramaximal doses of all full and partial D2 receptor agonists
      tested decreased serum prolactin levels with greater than 80%. While the
      intrinsic activities of the dopamine precursor 1-DOPA and of the full agonists
      (+)-3-PPP, 5-OH-DPAT, B-HT 920 (talipexole), apomorphine, and NPA (R-(-)-N-n
      propylnorapomorphine) were not affected by pretreatment with EEDQ, the effects of
      supramaximal doses of the partial agonists (-)-HW-165, TDHL (terguride), SDZ208
      911, (-)-3-PP) (preclamol), and SDZ 208-912 were reduced to 66%, 74%, 59%, 100%,
      and 100%, respectively. The effect of EEDQ on the intrinsic activity displayed by
      the various agonists corresponds inversely to the intrinsic efficacy displayed by
      the drugs in other models of D2 receptor function with one exception only; thus,
      the prolactin suppressive effect of (-)-3-PPP was more effectively antagonized by
      EEDQ than would have been predicted from the intrinsic efficacy usually
      attributed to the drug. Since the dose of EEDQ used in the present study has
      previously been shown not to decrease D2 receptor density in the pituitary as
      measured using in vivo radioligand binding, it is suggested that alkylation of D2
      receptors may change the conformation of the individual receptor complexes in a
      way that decreases the responsiveness to partial but not full agonists.

PMID- 1360152
TI  - Electrophysiological and electrochemical analysis of the secretion of ATP and
      noradrenaline from the sympathetic nerves in rat tail artery: effects of alpha 2
      adrenoceptor agonists and antagonists and noradrenaline reuptake blockers.
AB  - The aim of this study was to investigate whether or not nerve impulses release
      ATP and noradrenaline in parallel from the sympathetic nerve terminals of the rat
      tail artery. The extracellularly recorded excitatory junction current (EJC) was
      used to study, pulse by pulse, the release of ATP. An electrochemical method was
      used to study online the nerve stimulation-induced rise in the extracellular
      concentration of endogenous noradrenaline at the probe, a carbon fibre electrode
      (CF). This parameter, which does not directly represent noradrenaline release,
      but reflects release minus clearance, has been termed delta[NA]CF. The effects of
      a number of pharmacological agents on the EJCs were examined both at 0.1 and 2
      Hz, and the effects on the EJC response to 100 pulses at 2 Hz compared with that
      on the delta[NA]CF response. Clonidine and xylazine were used as alpha 2
      agonists, yohimbine and idazoxan as alpha 2-antagonists and desipramine and
      cocaine as blockers of noradrenaline reuptake. Most of these agents had unwanted
      side effects, especially at higher concentrations. However, clonidine and
      xylazine depressed at lower concentrations the EJC and delta[NA]CF responses to
      about the same extent; these effects were partially or completely reversed by
      yohimbine. Yohimbine or idazoxan did not affect the EJCs at 0.1 Hz but enhanced
      the EJC and delta[NA]CF responses to 100 pulses at 2 Hz to the same extent. All
      effects of desipramine (1 microM) seemed explainable as a result of block of
      noradrenaline reuptake, while cocaine (10 microM) in addition exerted an
      'unspecific' depressant (probably local anesthetic) effect. Under control
      conditions, both agents depressed the EJC but dramatically enhanced the
      delta[NA]CF response to 100 pulses at 2 Hz. Addition of yohimbine prevented the
      depressant effect of desipramine on the EJCs completely and reduced that of
      cocaine, but increased their effects on the delta[NA]CF response. These results
      are compatible with the view that ATP and noradrenaline are released in parallel
      from the sympathetic nerve terminals of this tissue. The different, and under
      some conditions even opposite, effects of desipramine or cocaine on the EJC and
      delta[NA]CF responses are explainable in terms of the known post-secretory
      effects of these agents.

PMID- 1360153
TI  - Activation of histamine H3 receptors produces presynaptic inhibition of neurally
      evoked cat nictitating membrane responses in vivo.
AB  - This study was undertaken in order to determine the potential role of
      prejunctional histamine H3 receptors in an in vivo adrenergic model system.
      Frequency-dependent nictitating membrane responses were elicited by sympathetic
      nerve stimulation in anesthetized cats. Systemic administration of the selective
      histamine H3 receptor agonist, (R)-alpha-methylhistamine (R alpha MeHA) produced
      a dose-related depression of amplitude of the evoked nictitating membrane
      responses with a threshold of about 10 micrograms/kg and maximal effect (50%
      depression at the lowest frequency; 0.5 Hz) seen at 100-300 micrograms/kg.
      Responses obtained with low frequency stimulation were more sensitive to
      depression by R alpha MeHA than were responses evoked with higher frequencies of
      stimulation. Larger doses of R alpha MeHA given to the same animals, failed to
      produce additional inhibition. R alpha MeHA depressed the amplitude of
      nictitating membrane responses evoked by either pre- or postganglionic nerve
      stimulation to an equivalent degree. This depressant action of R alpha MeHA was
      antagonized by pretreatment with the specific histamine H3 antagonist,
      thioperamide (3 mg/kg), but not by combined pretreatment with histamine H1 and H2
      blockers chlorpheniramine (300 micrograms/kg) and cimetidine (5 mg/kg).
      Intravenous administration of adrenaline (1-30 micrograms/kg) also produced
      graded nictitating membrane responses that were not altered by subsequent
      administration of R alpha MeHA. These results suggest that histamine H3 receptors
      are involved in the modulation of neurally evoked noradrenaline release in the
      cat nictitating membrane by an inhibitory presynaptic action.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1360154
TI  - Reversal by 3,3',5-triido-L-thyronine of the working memory deficit, and the
      decrease in acetylcholine, glutamate and gamma-aminobutyric acid induced by
      ethylcholine aziridinium ion in mice.
AB  - The effect of 3,3',5-triiodo-L-thyronine (T3) on working memory in ethylcholine
      aziridinium ion (AF64A)-treated mice was studied in a delayed non-matching to
      sample task using a T-maze. After behavioural testing was completed, mice were
      killed by microwave irradiation and regional brain levels of acetylcholine,
      aspartate, glutamate, glutamine, glycine, taurine, and gamma-aminobutyric acid
      (GABA) were measured by high-performance liquid chromatography with
      electrochemical detection. Treatment with AF64A (7 nmol, i.c.v.) produced a
      deficit in working memory performance in the non-matching to sample task at 30 s
      delay, and decreased acetylcholine, glutamate, and GABA levels in the
      hippocampus, but not in the septum and cerebral cortex. Administration of T3 (0.3
      mg/kg, p.o., once daily for 6 days) to AF64A-treated animals improved the deficit
      in working memory performance and reversed the decrease in acetylcholine,
      glutamate, and GABA levels in the hippocampus. These results indicate that the
      deficit in performance induced by AF64A can be improved by T3 administration.

PMID- 1360155
TI  - Functional changes in neuropeptide Y- and somatostatin-containing neurons induced
      by limbic seizures in the rat.
AB  - The influence of sustained epileptic seizures evoked by intraperitoneal injection
      of kainic acid on the gene expression of the neuropeptides somatostatin and
      neuropeptide Y and on the damage of neurons containing these peptides was studied
      in the rat brain. Injection of kainic acid induced an extensive loss of
      somatostatin and, though less pronounced, of neuropeptide Y neurons in the inner
      part of the hilus of the dentate gyrus. Neuropeptide Y-immunoreactive neurons
      located in the subgranular layer of the hilus, presumably pyramidal-shaped basket
      cells, were spared by the treatment. Although neuropeptide Y messenger RNA was
      not detected in granule cells of control rats, it was found there after kainic
      acid seizures at all time intervals investigated (12 h to 90 days after injection
      of kainic acid). High concentrations of neuropeptide Y messenger RNA were
      especially observed 24 h after injection of kainic acid. At this time
      neuropeptide Y messenger RNA was also transiently observed in CA1 pyramidal
      cells. Neuropeptide Y synthesis in granule cells in turn gave rise to an intense
      immunoreactivity of the peptide in the terminal field of mossy fibers which
      persisted for the entire time period (90 days) investigated. In addition,
      neuropeptide Y messenger RNA concentrations were also drastically elevated in
      presumptive basket cells located at the inner surface of the granule cell layer,
      especially at the "late" time intervals investigated (30-90 days after kainic
      acid). These data support the concept that extensive activation of granule cells
      by limbic seizures contributes to the observed neuronal cell death in CA3
      pyramidal neurons and interneurons of the hilus. Consecutively, basket cells
      containing neuropeptide Y and presumably GABA might be activated and participate
      in recurrent inhibition of granule cells. Neuropeptide Y-immunoreactive fibers
      observed in the inner molecular layer at "late" time intervals after kainic acid
      may result either from collateral sprouting of mossy fibers or from basket cells
      extensively expressing the peptide. It is speculated that neuropeptide Y
      synthesized and released at a high rate from granule cells and basket cells may
      exert a protective action against seizures.

PMID- 1360156
TI  - Kinetics and mechanism of degradation of a cyclic hexapeptide (somatostatin
      analogue) in aqueous solution.
AB  - A highly active cyclic hexapeptide analogue of somatostatin, Cyclo(N-Me-L-Ala-L
      Tyr-D-Trp-L-Lys-L-Val-L-Phe), L-363,586, was found to improve the control of
      postprandial hyperglycemia in diabetic animals when given in combination with
      insulin. The compound is reported to be relatively stable in blood, nasal cavity,
      and intestinal lumen but undergoes rapid degradation in aqueous solution. The
      objective of this study was to elucidate the degradation mechanisms based on the
      kinetic data and the structure of the degradation products. Both pH and
      temperature had a profound influence on the instability of the peptide in aqueous
      solution. The data indicated that the peptide was most stable at a pH of about
      4.7. The pH-rate profile exhibited specific acid catalysis at a pH less than 3.0
      and base catalysis above pH 10.5. The kinetic pKa was determined to be 9.7. This
      pKa could be attributed to the tyrosine residue. The mechanisms of degradation
      under acidic and alkaline conditions appear to be different. Identification of
      the fragments obtained using mass spectrometry and amino acid sequencing suggest
      that the cyclic compound was cleaved to yield a linear fragment, which underwent
      further cleavage at both peptide linkages alpha to the tryptophanyl residue. The
      indole group of that residue is probably the potential nucleophile attacking the
      adjacent carbonyls. A rate equation for the degradation of the hexapeptide has
      been proposed.

PMID- 1360157
TI  - Morphine and the endogenous opioid dynorphin in the brain attenuate digoxin
      induced arrhythmias in guinea pigs.
AB  - The effects of the opioid receptor agonists morphine and dynorphin on digoxin
      induced arrhythmias were examined in guinea pigs that had received intravenous
      digoxin (50 mu/kg bolus plus 500 mu/kg/hr intravenously). Animals received either
      morphine (50 or 100 micrograms/kg) or dynorphin A(1-13) (50 or 100 micrograms/kg)
      or saline (the diluent) into the lateral cerebral ventricle
      (intracerebroventricularly) prior to digoxin. Morphine and dynorphin produced
      significant (P < 0.05) dose-dependent increases in the threshold of digoxin
      induced arrhythmias. The mean digoxin dose at the development of fatal
      arrhythmias was 775 +/- 42 micrograms/kg in the control group but was
      significantly higher namely 958 +/- 45 micrograms/kg after 100 micrograms/kg of
      morphine ICV, and 984 +/- 47 micrograms/kg after 100 micrograms/kg of dynorphin A
      (1-13) intracerebroventricularly. In the absence of digoxin, the highest doses of
      each of these opioids did not produce arrhythmias. Changes in blood pressure and
      heart rate were unlikely explanations for the observed actions of these opioids
      as morphine accentuated the increase in blood pressure that accompanied digoxin
      while dynorphin was associated with a lower blood pressure with digoxin, despite
      similar effects on arrhythmias. In the control group, fatal digoxin-induced
      arrhythmias were ventricular tachyarrhythmias in two-thirds of cases and complete
      heart block in the rest. Morphine and dynorphin reduced the development of
      ventricular tachyarrhythmias. The role of the cholinergic system was explored,
      with morphine, utilizing atropine sulfate which crosses the blood brain barrier
      and atropine methylnitrate which does not enter the CNS. Atropine sulfate but not
      atropine methylnitrate reversed the effects of morphine on digoxin-induced
      arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360158
TI  - Behavioral effects of dilazep on cholinergic, dopaminergic, and purinergic
      systems in the rat.
AB  - This study examined the effects of 1,4-bis[3-(3,4,5-trimethoxy benzoyloxy)
      propyl] perhydro-1,4-diazepine (dilazep; Comelian) on central dopaminergic,
      cholinergic, and purinergic neuronal systems in rats. Intraperitoneal injections
      of dilazep (1-5 mg/kg) produced yawning responses, the most effective dose being
      2 mg/kg. Dilazep potentiated physostigmine-induced yawning but not pilocarpine-
      and bromocriptine-induced yawning. Dilazep-induced yawning was not affected by
      low doses of haloperidol or sulpiride, but was completely inhibited by atropine,
      a muscarinic M1 receptor antagonist. Dilazep-induced yawning, as well as
      physostigmine-induced yawning, were markedly inhibited by pretreatment with SK &
      F 38393, a dopamine D1 receptor agonist, and were potentiated by SCH23390, a
      dopamine D1 receptor antagonist that alone does not elicit yawning. Caffeine, an
      adenosine receptor antagonist, inhibited dilazep- and physostigmine-induced
      yawning responses but N6-cyclohexyl adenosine (CHA) and N6-(L-phenylisopropyl,
      adenosine (L-PIA), adenosine A1 receptor agonists, were inactive. These results
      suggest that because the effects of dilazep on central cholinergic neurons are
      similar to those of physostigmine dilazep may potentiate indirectly the action of
      endogenous acetylcholine. Cholinergic neurons activated by dilazep may be
      modulated by postsynaptic dopamine D1 receptor activity but may not be affected
      by dopamine D2 receptor activity. Furthermore, the stimulatory effects of dilazep
      on cholinergic neuron may not be due to an inhibition of dopamine D1 receptors
      via purinergic (adenosine A1 receptor) stimulation by dilazep.

PMID- 1360159
TI  - Anxiolytic-like effects of alpha-2-adrenoceptor agonists on conflict behavior in
      the rat: pre- versus postsynaptic receptor mechanisms.
AB  - The effects of acute pretest administration and chronic posttest administration
      of clonidine or the selective alpha 2-adrenoceptor agonist UK-14,304 on conflict
      behavior were investigated. In daily 10-min sessions, water-deprived rats were
      trained to drink water from a tube that was occasionally electrified (0.25 mA);
      electrification was signaled by a tone. Prior to treatment, subjects accepted 25
      30 shocks/session (punished responding) and consumed approximately 12-15
      ml/session (unpunished responding). Acute pretest administration of clonidine or
      UK-14,304 did not increase punished responding. In contrast, chronic posttest
      clonidine administration (40 micrograms/kg, IP, twice daily for 8 weeks) resulted
      in a robust and time-dependent increase in punished responding (60-70
      shocks/session) relative to saline-treated controls. Moreover, the selective
      alpha 2-adrenoceptor agonist UK-14,304 also increased punished responding when
      administered chronically (1.0 mg/kg, BID). Administration of the noradrenergic
      neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine HCl (DSP4, 65 mg/kg, IP)
      significantly decreased punished responding in control conditioned suppression of
      drinking sessions. The anticonflict effect associated with chronic posttest
      clonidine treatment was not altered by DSP4 pretreatment. These findings suggest
      that chronic posttest alpha 2-adrenoceptor agonist treatment produces an
      anticonflict effect independent of its actions at presynaptic alpha 2
      adrenoceptors.

PMID- 1360160
TI  - Pertussis toxin-mediated ribosylation of G proteins blocks the hypnotic response
      to an alpha 2-agonist in the locus coeruleus of the rat.
AB  - Biologic responses mediated by adrenoceptors are transduced by a receptor
      effector mechanism that involves a guanine nucleotide binding protein (G
      protein). Recently, we determined that the transduction mechanism for the
      hypnotic response to dexmedetomidine, a highly selective alpha 2-agonist, is
      located in the locus coeruleus (LC) of the rat. In this study, we examined the
      role of pertussis toxin-sensitive (PTX) G proteins in the LC for the hypnotic
      response to dexmedetomidine. The LC of rats were stereotactically cannulated and
      treated with PTX, 0.34 micrograms, or vehicle. Five days later, the hypnotic
      response to dexmedetomidine, 7 micrograms into the LC or 50 micrograms.kg-1 IP,
      was tested. On the following day, the LC was harvested and assayed to determine
      whether the G proteins had been ribosylated by pretreatment with PTX in vivo.
      Quantitative immunoblotting of G0 alpha, Gi alpha 1,2, and Gi alpha 3, the alpha
      subunit of three PTX-sensitive proteins, was also performed. In vivo treatment
      with PTX into the LC blocked the hypnotic response to LC-administered
      dexmedetomidine and, to a lesser extent, IP-administered dexmedetomidine. The in
      vivo PTX treatment effectively ribosylated the G proteins. No alteration in the
      amount of the different species of PTX-sensitive alpha-subunit was produced by in
      vivo PTX treatment. These data suggest a pivotal role for PTX-sensitive G
      proteins in the LC in the hypnotic response to alpha 2-agonists in the rat.

PMID- 1360161
TI  - Activation of alpha 2-adrenoceptors suppresses excessive wheel running in the
      semistarvation-induced hyperactive rat.
AB  - Male Wistar rats were housed in cages linked to running wheels and fed on a
      schedule designed to reduce their body weight by 20-30%. During this period of
      semistarvation, rats increased their daily running wheel activity (RWA) by up to
      30 km/day. RWA could be kept at this level provided that body weight was kept
      constant. Different alpha-adrenergic agonists and antagonists were tested for
      their effects on RWA and it was found that RWA could be suppressed only by
      agonists that display high affinity for the alpha 2-receptor (clonidine and
      guanfacine). Neither antagonist had an effect on RWA. Clonidine's inhibiting
      effect on RWA was prevented by pretreatment with yohimbine, which also has high
      affinity for alpha 2-receptors. From these results, we conclude that
      semistarvation-induced hyperactivity can be blocked by alpha 2-agonists. In view
      of this result and those that were obtained in previous studies, a theoretical
      model for the development of semistarvation-induced hyperactivity will be
      presented.

PMID- 1360162
TI  - Investigation of MDMA-related agents in rats trained to discriminate MDMA from
      saline.
AB  - To determine whether metabolite-related analogs of N-methyl-1-(3,4
      methylenedioxyphenyl)-2-aminopropane (MDMA) produce stimulus effects similar to
      those of the parent compound, and to determine the structural requirements
      associated with the MDMA stimulus, several MDMA analogs were examined in tests of
      stimulus generalization using rats trained to discriminate 1.5 mg/kg MDMA from
      saline. Although several of the analogs produced up to 50-60% MDMA-appropriate
      responding, none [with the exception of N-methyl-1-(4-methoxyphenyl)-2
      aminopropane (PMMA)] resulted in stimulus generalization. The partial
      generalization, coupled with the possible reduced ability of certain of the
      agents to penetrate the blood-brain barrier relative to MDMA, suggests that these
      agents are not behaviorally inactive. PMMA, although not a metabolite of MDMA, is
      closely related in chemical structure to MDMA and its metabolites; PMMA produces
      > 80% MDMA-appropriate responding and is approximately three times more potent
      (ED50 = 0.2 mg/kg) than MDMA itself (ED50 = 0.76 mg/kg). PMMA is a newer
      scheduled substance with an as yet unknown mechanism of action; however, on the
      basis of the stimulus generalization observed PMMA may share some behavioral and
      mechanistic similarity with MDMA. These results also indicate that an intact
      methylenedioxy ring, such as that found in MDMA but absent in PMMA, is not a
      prerequisite for MDMA-like activity and further support the notion that ring
      opened MDMA metabolites may produce effects that contribute to the actions of
      MDMA.

PMID- 1360163
TI  - Comparison of behavioral and central BDZ binding profile in three rat lines.
AB  - The performance of three widely used rat lines (Sprague-Dawley, Wistar, and Long
      Evans hooded) were evaluated in behavioral test systems that are sensitive to
      benzodiazepines. The in vivo effects of flunitrazepam and the brain [3H]Ro 15
      1788 binding were determined and compared in these rat lines. The behavioral end
      points evaluated in this study were anxiolysis, measured using the automated
      elevated plus-maze; sedation by modification of locomotor activity; hyperphagia
      following food deprivation; protection for pentylenetetrazol-induced convulsions;
      and hypothermia. There were comparable results in the hypnotic, hypothermic,
      anticonvulsant, and feeding tests in these lines following flunitrazepam
      administration. However, the behavior of the Long Evans hooded rat was most
      amenable to the detection of drug-induced changes in the anxiety test. There was
      no difference in the maximum number of binding sites (Bmax) or the affinity (Ki)
      of the Ro 15-1788 or flunitrazepam binding in either the cerebellum or whole
      brain (minus cerebellum) in the three rat lines as determined by the competitive
      binding against [3H]Ro 15-1788. Thus, while these rat lines exhibited similar
      behavioral profiles in most tests the modest differences in the baseline
      responses and the ability to detect anxiolysis at lower doses of flunitrazepam
      observed with Long Evans hooded rats makes them particularly suited for these
      types of studies.

PMID- 1360164
TI  - Raclopride decreases sucrose intake of rat pups in independent ingestion tests.
AB  - To investigate the role of dopaminergic activity at D2 receptors in the mediation
      of the positive reinforcing effect of sucrose on ingestion in preweanling rats,
      we tested the effects of the D2 antagonist, raclopride, on the intake of 10%
      sucrose of rats on postnatal days (PN) 7, 14, and 21. Intake was measured during
      independent ingestion tests in which pups licked sucrose from the floor of a
      beaker and during oral catheter tests in which sucrose was continuously infused
      through an anterior, sublingual, oral catheter. Rats were tested once to
      eliminate the possibility that repeated test experience would affect the response
      to raclopride. Pretreatment with raclopride resulted in decreased intake in
      independent ingestion (II) tests, but not in oral catheter (OC) tests on PN 7,
      14, and 21. The inhibition of intake was not due to a generalized motor deficit
      because raclopride did not affect latency to eat, time-sampled activity scores,
      or latency to withdraw the hindlimb from a raised position. These results
      demonstrate that dopaminergic activity at D2 receptors is necessary for the
      positive reinforcing effect of sucrose that maintains ingestion in the II test
      but not in the OC test.

PMID- 1360165
TI  - Stimulus effects of d-amphetamine 1: DA mechanisms.
AB  - As part of a continuing effort to assess the role of monoaminergic neuronal
      systems in the subjective effects of CNS stimulants, 10 rats trained to
      discriminate 1.0 mg/kg d-amphetamine from saline were treated with compounds that
      act through different dopaminergic mechanisms. In substitution (generalization)
      tests, 20 mg/kg of the dopamine (DA) uptake inhibitor GBR 12909 mimicked the
      training drug completely; at a dose of 15 mg/kg, GBR 12909 substituted for d
      amphetamine incompletely. Neither the D1 agonist SK&F 38393 (1, 10 mg/kg) nor the
      D2 agonist quinpirole (LY 171555; 0.05-0.2 mg/kg) had amphetamine-like effects.
      When given in combination with the training drug, the D1 antagonist SCH 23390
      blocked the amphetamine cue completely at a dose of 0.05 mg/kg but did not have
      significant effects at higher or lower doses; the D2 antagonist metoclopramide
      did not block d-amphetamine at any dose tested (1-5 mg/kg). These data indicate
      that: a) The discriminable effects of d-amphetamine are due, at least in part, to
      inhibition of DA uptake; b) direct stimulation of either D1 or D2 receptor sites
      is not sufficient to evoke d-amphetamine-like responding; and c) blockade of D1
      receptors attenuates the subjective effects of d-amphetamine to a greater extent
      than blockade of D2 receptors.

PMID- 1360166
TI  - Donor leukocyte migration following extremity transplantation in an experimental
      model.
AB  - In an effort to further define the immunologic mechanisms leading to acute
      composite-tissue allograft rejection, the migratory patterns of donor leukocytes
      were evaluated. Using a rat model, 52 orthotopic vascularized hindlimb
      transplants were performed in strains representing major histocompatibility
      mismatches. In order to evaluate the effect of allogeneic skin on limb rejection,
      all donor skin was removed in a second group of allografts. Recipient lymphoid
      organs were examined during the week following transplantation for antigen
      presenting cells using a donor-specific class II monoclonal antibody. Donor
      leukocytes, with dendritic cell morphology, were identified in recipient spleen
      and lymph nodes draining the allograft. Significantly higher numbers of donor
      leukocytes were present during postoperative days 1 through 4 for both groups.
      Association of these important passenger leukocytes with host T-lymphocytes may
      represent the site of initiation of the immune response.

PMID- 1360167
TI  - Seasonal relapses in affective disorder in the Tropics: a prospective follow-up
      of 12 patients.
AB  - Seasonal relapses of affective disorder are known. We report 12 patients who had
      season-linked relapses during a prospective follow-up period of 4 years. There
      were both winter and summer relapses of mania and depression. The centre is in
      the tropical zone, with lesser variation of sunshine and temperature than in more
      extreme latitudes. This may inference the pattern of relapse in affective
      disorder. Differences in relapses between tropical and temperate zones need to be
      investigated.

PMID- 1360169
TI  - Imaging methods for medullary thyroid cancer.

PMID- 1360168
TI  - Screening for MEN 2 with biochemical and genetic markers.

PMID- 1360170
TI  - Surgical management of MEN 2.

PMID- 1360171
TI  - Restriction fragment length polymorphism in four virulence-associated genes of
      Listeria monocytogenes.
AB  - We observed restriction fragment length polymorphism in 4 genes of Listeria
      monocytogenes associated with virulence. Using the polymerase chain reaction
      (PCR) and primers derived from published sequences, we amplified the following
      genes: hlyA coding for listeriolysin O, iap coding for a putative invasion
      associated factor, mpl coding for a metalloprotease, and the prfA gene that
      positively regulates the hylA gene. PCR-amplified DNA were cut with several
      restriction endonucleases, and the restriction profiles from 29 strains,
      representing 6 serovars (serovars 1/2a, 1/2b, 1/2c, 3a, 3b and 4b) were compared.
      Based on these restriction profiles, the strains were categorized into 2
      subgroups: one group contained all 10 strains of serovars 1/2a, 1/2c and 3a, the
      other group contained all 19 strains of serovars 1/2b, 3b and 4b. This division
      is in complete agreement with multilocus enzyme electrophoretic analysis data
      which divide the species into the same 2 subgroups. Whether the differences
      observed in the nucleotide sequences of the 4 virulence-associated genes for the
      2 subgroups of L. monocytogenes represent salient variations in pathogenic
      mechanisms is not known.

PMID- 1360172
TI  - Influence of sympathetic and parasympathetic substances in clinical
      concentrations on human nasal ciliary beat.
AB  - The effect of autonomic substances on ciliary beat in mucosal biopsies from the
      normal human nose was studied. The influence on ciliary beat frequency (CBF) as
      well as on ciliary beat harmony was measured photoelectrically. The sympathetic
      beta-agonist isoprenaline was found to have a stimulatory effect on CBF, whereas
      the alpha-agonist xylometazoline reduced CBF and ciliary beat harmony. The
      parasympathetic agonist carbachol had a positive effect on CBF. The sympathetic
      antagonists timolol (beta) and phentolamine (alpha) as well as the
      parasympathetic antagonist atropine had no effect. The effect of the agonists on
      ciliary beat was absent when they were administered in combination with their
      specific antagonists. These experiments indicate that, in clinical
      concentrations, the autonomic substances modify ciliary beat by a direct effect
      on the ciliated cells.

PMID- 1360173
TI  - Successful pancreatojejunal anastomosis for pancreatoduodenectomy.
AB  - A series of 100 patients underwent pancreatoduodenectomy for carcinoma of the
      head of the pancreas (36 patients), the bile duct (19 patients), the gallbladder
      (14 patients), the papilla of Vater (13 patients), the duodenum (seven patients),
      the stomach (seven patients) or the colon (one patient), or for chronic
      pancreatitis (two patients) and adenomyoma of the bile duct (one patient) between
      October 1983 and December 1990. The operative morbidity and mortality rates were
      27 and 6 percent, respectively, and failure of the pancreatojejunal anastomosis
      was the most common post-operative complication (16 patients). Anastomotic
      leakage correlated significantly with the quality of the pancreatic remnant and
      the preoperative technique used (p < 0.01). The leakage rate in 34 patients with
      fibrotic pancreatic tissue was 5.8 percent (two of 34) and was significantly less
      than that in 66 patients with a normal pancreatic remnant (21.2 percent). Forty
      seven patients underwent direct anastomosis between the main pancreatic duct and
      the jejunum, using mucosa to mucosa sutures and a pancreatic duct drain tube as
      well as a single layer of sutures between the pancreatic tissue and the jejunum.
      Only two patients had a pancreatic fistula (4.2 percent) and the incidence was
      significantly less than that in 53 patients who received the usual technique of
      double-layer sutures between the pancreatic remnant and the jejunum without a
      direct anastomosis to the main pancreatic duct (26.4 percent, p < 0.01).

PMID- 1360174
TI  - Two new nonsense mutations in type Ia antithrombin III deficiency at Leu 140 and
      Arg 197.
AB  - Using polymerase chain reaction-single strand conformation polymorphism (PCR
      SSCP) and DNA sequencing, the molecular basis of hereditary type Ia antithrombin
      III (AT III) deficiency was disclosed in two families. One mutation was a change
      from T to A in the codon of TTA for Leu 140 forming a stop codon of TAA, which
      was confirmed by mutated primer-mediated PCR-HindIII digestion. The application
      of this method demonstrated that all four affected members had the mutant allele
      in a heterozygous state and that none of unaffected subjects had this mutation.
      Another mutation in the second family was a change from C to T in the codon of
      CGA for Arg 197 also forming a stop codon of TGA, which was confirmed by PCR
      HaeIII digestion. Based on these, it was concluded that the two new nonsense
      mutations in the AT III gene in a heterozygous state are the molecular basis of
      hereditary type Ia AT III deficiency.

PMID- 1360175
TI  - [Growth hormone deficiency: diagnosis and treatment].
AB  - Growth hormone (GH) and thyroxine are the major growth promoting hormones in
      postnatal life. The pulsatile pattern of GH-release by the anterior pituitary is
      regulated by the interaction of stimulating and inhibiting hormones and
      influenced by physiological and pharmacological factors. GH promotes longitudinal
      bone growth mainly through activation of insulin-like growth factor I (IGF-I),
      but there may also be a direct effect. The most important clinical feature of
      growth hormone deficiency (GHD) is a low growth velocity resulting in short
      stature. In addition to retardation of bone maturation many GH-deficient children
      exhibit a number of typical, clinical characteristics. The diagnosis GHD can be
      confirmed by performing GH-stimulation tests and IGF-I measurements. However, the
      maximal GH-response to provocative stimuli is a poor indicator of the spontaneous
      GH-secretion. Classifications and etiology of GHD are given. Since 1958 GH
      deficient children are treated with human GH with initially disappointing results
      regarding attained final height. Early diagnosis and treatment and optimization
      of GH-dose, mode of administration and injection frequency might improve final
      height. In The Netherlands the currently used GH-dose is 12-14 IU/m2/week in 6 or
      7 daily doses administered subcutaneously. Ongoing retrospective and prospective
      studies serve to determine optimal treatment schedules. Up to now, important
      adverse effect of GH-therapy with the current GH-doses in GH-deficient children
      are not known. The beneficial effects of long-term GH-treatment of GHD adults is
      at present subject to ongoing investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360176
TI  - Extracellular alkalinity exacerbates injury of cultured cortical neurons.
AB  - BACKGROUND AND PURPOSE: We have previously shown that extracellular acidity
      protects cultured fetal murine neocortical neurons from glutamate toxicity and
      combined oxygen-glucose deprivation injury, an action at least in part mediated
      by reduction in N-methyl-D-aspartate receptor activation. We now investigate the
      effect of extracellular alkalinity on both glutamate neurotoxicity and injury due
      to combined oxygen-glucose deprivation. METHODS: The effects of extracellular
      alkalinity during injury induced by exposure of murine neocortical cultures to
      glutamate (0.5 mM for 5 minutes) or oxygen-glucose deprivation are characterized
      morphologically and quantitated by efflux of lactate dehydrogenase from both
      neurons and glia to the bathing medium. Calcium accumulation is measured with
      calcium-45. RESULTS: Moderate extracellular alkalinity is well tolerated by
      cortical cells but significantly potentiates both glutamate neuronal toxicity and
      oxygen-glucose deprivation neuronal injury. In contrast, glial viability in the
      face of combined oxygen-glucose deprivation is little affected by extracellular
      alkalinity. Increased accumulation of calcium-45 during oxygen-glucose
      deprivation in alkalotic medium and blockade of this increase by MK-801 is
      demonstrated. CONCLUSIONS: These observations suggest that alkaline pH can
      exacerbate excitotoxic neuronal injury, most likely because of increased N-methyl
      D-aspartate receptor activation. Metabolic alkalosis of any etiology may
      sensitize neurons to ischemic injury and potentiate reperfusion injury.

PMID- 1360178
TI  - Animal models of retrovirus-associated malignancies.

PMID- 1360177
TI  - [Glutamine metabolism by rumen microorganisms: effect of monensin].
AB  - Transformation of glutamine of mixed population of microorganisms-symbionts is
      demonstrated. Protection of glutamine and its intermediates (glutamate and
      pyroglutamate) under the influence of ionophore (monensin) is found. It is
      accompanied by the reduced (by 30-70 per cent and more) levels of ammonia
      formation, total VFA, acetate, butyrate, pH, alpha-ketoglutarate dehydrogenase
      and glutamine synthetase at parallel increase of L-aspartate and L-alanine: 2
      oxoglutarate, aminotransferase activity, redox potential of stability of protein
      content. It is suggested that the rapid change of Eh level on the 24th hour of
      incubation reflects the main stage of pyroglutamate formation being one of the
      final products of glutamine degradation when monensin is used. Ionophore affects
      first of all the inhibition of metabolic processes in gram-positive rumen
      microorganisms.

PMID- 1360179
TI  - Characteristics of the T cell-mediated immune response to maedi-visna virus.
AB  - Virus-specific T cell-mediated immunity was investigated in healthy sheep
      persistently infected with the ruminant lentivirus maedi-visna. Visna-specific
      lymphocyte proliferation was demonstrated in response to both purified virions
      and recombinant p25, the major core protein of maedi-visna virus. The responding
      T cell population in this assay was mainly of the CD4+ phenotype, although in
      some individuals CD8+ T cells were also shown to respond to visna antigen in this
      system.

PMID- 1360180
TI  - Detection of protein kinase homologues and viral RNA-binding domains utilizing
      polyclonal antiserum prepared against a baculovirus-expressed ds RNA-activated
      68,000-Da protein kinase.
AB  - The P68 protein kinase (referred to as P68 based on its M(r) of 68,000 in human
      cells) is a serine/threonine kinase induced by interferon treatment and activated
      by dsRNAs. The kinase is under tight controls in virus-infected cells since once
      activated, it phosphorylates its natural substrate eukaryotic initiation factor 2
      (elF-2), leading to potential limitations in functional elF-2 and decreases in
      protein synthesis initiation. To further delineate the molecular mechanisms
      underlying kinase regulation, we attempted to express the P68 protein kinase in
      insect cells using a baculovirus vector. Repeated efforts to isolate recombinant
      baculoviruses containing a wild-type kinase failed, whereas recombinants
      expressing a nonfunctional kinase with a catalytic domain II mutation were
      readily isolated. When used to infect Spodoptera frugiperda cells, the
      recombinant virus expressed the exogenous mutant protein at almost 5-10% of the
      total proteins synthesized. We then purified the kinase by immunoaffinity
      chromatography to raise monospecific antiserum which recognized not only the
      human native wild-type P68, but also kinase homologues in murine, bovine, and
      monkey cells as determined by immunoblot and immunoprecipitation analysis.
      Fortunately, kinase function also could be assayed using this antibody since the
      human and nonhuman kinase homologues, present in immunoprecipitates, were
      autophosphorylated and phosphorylated the natural substrate, elF-2 alpha.
      Further, this antiserum recognized epitopes throughout the molecule including the
      amino and carboxyl termini in contrast to the available monoclonal antibody. In
      vitro assays using the polyclonal antibody revealed the importance of the amino
      terminus, especially amino acids 1-97, in the binding of the kinase to viral RNA
      activators and inhibitors. Finally, we determined that the P68 amino terminus was
      both necessary and sufficient for binding dsRNA as we were able to transfer dsRNA
      binding properties to a reporter gene product previously unable to bind RNA.

PMID- 1360181
TI  - HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase.
AB  - Human immunodeficiency virus (HIV-1) infection in the human brain leads to
      characteristic neuropathological changes, which may result indirectly from
      interactions of the envelope glycoprotein gp120 with neurons and/or glial cells.
      We therefore investigated the binding of recombinant gp120 (rgp120) to human
      neural cells and its effect on intracellular signalling. Here we present evidence
      that rgp120, besides binding to galactocerebroside or galactosyl-sulfatide,
      specifically binds to a protein receptor of a relative molecular mass of
      approximately 180,000 Da (180 kDa) present on the CD4-negative glioma cells D-54,
      but not on Molt4 T lymphocytes. Binding of rgp120 to this receptor rapidly
      induced a tyrosine-specific protein kinase activity leading to tyrosine
      phosphorylation of 130- and 115-kDa proteins. The concentration of intracellular
      calcium was not affected by rgp120 in these cells. Our data suggest a novel
      signal transducing HIV-1 gp120 receptor on CD4-negative glial cells, which may
      contribute to the neuropathological changes observed in HIV-1-infected brains.

PMID- 1360183
TI  - Membrane alterations linked to early interactions of HIV with the cell surface.
AB  - Ultrastructural studies suggest that cell surface alterations occur early during
      the course of HIV-1 infection of CD4+T-lymphoblastoid cells. Attachment and
      penetration of HIV resulted in formation of membrane discontinuities and pores
      and "ballooning." Distention of the endoplasmic reticulum occurred in some cells
      within the first hour after HIV infection, and this correlated with the numbers
      of virions bound at the cell surface. These results suggest that HIV virion
      components may directly damage the cell membrane.

PMID- 1360182
TI  - Immediate-early, early, and late RNAs in bovine herpesvirus-4-infected cells.
AB  - We have begun to identify immediate-early (IE), early (E), and late (L) genes of
      BHV-4 by analysis of cytoplasmic polyadenylated RNA transcribed from the BHV-4
      genome over the course of infection and in the presence of cycloheximide or
      phosphonoacetic acid. Labeled cDNA prepared from RNA isolated at different times
      was hybridized with Southern blots of viral DNA to show which regions of the
      genome are transcribed at different times. In a second series of experiments,
      radiolabeled cloned restriction fragments representing the entire BHV-4 genome
      were hybridized separately to RNA on Northern blots to determine the number and
      sizes of transcripts at different times. As expected, with increasing time after
      infection, more portions of the BHV-4 genome are transcribed and a larger number
      and a greater abundance of viral transcripts are present. RNA transcribed from
      terminal repeats was not detectable at any time. However, similarity in size of
      RNA transcribed from opposite ends of the unique region of the genome late in
      infection suggests that RNA is transcribed over the fused ends of the genome, and
      terminal repeats are removed during RNA processing. Identification of IE, E, and
      L transcripts by this analysis lays the foundation for further study of specific
      BHV-4 transcripts and genes.

PMID- 1360184
TI  - Fibroplasia and Cholestasis: Pathogenic Factors of Chronic Liver Diseases.
      Workshop. Heidelberg, 15 June 1991.

PMID- 1360185
TI  - Somatostatin inhibits the norepinephrine-activated calcium channels in rMTC 6-23
      cells: possible involvement of a pertussis toxin-sensitive G-protein.
AB  - The mechanisms by which somatostatin inhibits hormone release are complex and
      involve, among other things, reduction of both intracellular cAMP and
      intracellular calcium. We studied the influence of the long-acting somatostatin
      analogue octreotide on norepinephrine (NE)-induced changes in intracellular
      calcium ([Ca2+]i) in fura-2 loaded single cells of a rat medullary carcinoma cell
      line, rMTC 6-23. Increases in the extracellular calcium concentration ([Ca2+]e)
      induced a sudden rise in [Ca2+]i which could be blocked by EGTA or the calcium
      channel blocker verapamil. NE evoked a similar increase in [Ca2+]i, which also
      could be blocked by the addition of EGTA or verapamil. Octreotide prevented or
      reversed the NE-induced increase in [Ca2+]i. Pretreatment of the cells with
      pertussis toxin abolished the inhibitory effect of octreotide. Thus we conclude
      that the NE-induced rise in [Ca2+]i is due to an influx of [Ca2+]e, most probably
      through voltage-dependent calcium channels. Octreotide inhibits the NE-stimulated
      rise in [Ca2+]i by a pertussis toxin-sensitive G-protein, most probably through a
      direct effect on NE-activated calcium channels.

PMID- 1360186
TI  - Sebaceous gland and sweat gland carcinomas of the skin. Clinicopathological study
      and significance of c-erbB-2 oncoprotein expression.
AB  - Thirteen sebaceous gland carcinomas and 10 sweat gland carcinomas were examined
      to elucidate any important histological parameters influencing their prognosis,
      and the relationship between immunohistochemical expressions of c-erbB-2
      oncoprotein and survival of the patients was analyzed. Sebaceous gland carcinomas
      with vacuolated cytoplasm in more than 50% of whole tumor area, with necrosis,
      and without lymphoid cell infiltration in tumor nests and stroma had a higher
      incidence of tumor recurrence and tumor-related death than tumors with vacuolated
      cytoplasm in 50% or less of whole tumor area (p < 0.01), without necrosis, and
      with lymphoid cell infiltration in tumor nest and stroma (p < 0.05). Sweat gland
      carcinomas of all cases with fatal outcomes demonstrated tubular differentiation
      in 20% or less of whole tumor area, lymphatic permeation and desmoplastic
      reaction. Three sebaceous gland carcinomas and three sweat gland carcinomas were
      positive for c-erbB-2 oncoprotein. Two of three sebaceous gland carcinomas, and
      all three sweat gland carcinomas developed tumor recurrence and ended in tumor
      related deaths. Sweat gland carcinomas with c-erbB-2 expression had significantly
      shorter survival than those with negative immunostain (p < 0.01). Cytoplasmic
      appearance, tumor necrosis, and lymphoid cell infiltration in tumor nests and
      stroma of sebaceous gland carcinoma, and tubular differentiation, lymphatic
      permeation, and growth patterns of sweat gland carcinoma are considered to
      closely correlate to the prognosis. Immunohistochemically detected c-erbB-2
      oncoprotein may be an indicator of bad prognosis.

PMID- 1360188
TI  - Ion Pumps, Structure and Mechanism. Satellite symposium of the 15th International
      Congress of Biochemistry. Gothenburg, Sweden, August 12-14, 1991.

PMID- 1360189
TI  - Pancreatic islet cell regeneration and growth. Proceedings of the Diabetes
      Institute Conference. Norfolk, Virginia, June 22-23, 1991.

PMID- 1360187
TI  - Effects of tissue fixation and processing on proliferating cell nuclear antigen
      (PCNA) immunohistochemistry.

PMID- 1360190
TI  - Expression of growth factors in a pancreatic islet regeneration model.
AB  - In this model of pancreatic regeneration, the initial trophic effect of
      cellophane wrapping is upon the ductular-epithelium, as shown by autoradiographic
      analysis following a single pulse of 3H-TdR. The uptake of 3H-TdR by ductular
      cells is maximal approximately 4 weeks before the peak uptake of the label by
      islet cells. Six weeks after the pulse, most of the label is contained in
      differentiating islet cells, not ductular cells. This phenomenon suggests that
      wrapping of the pancreas induces "progenitor" cells to differentiate along the
      line of endocrine cells. The essentially negative observations on REG gene
      expression in the regenerating hamster pancreas indicate that the message for
      this gene is either not involved in the regeneration process or that it is
      sufficiently different from the rat gene (a rat control probe was used) that it
      precludes detection by our methodology. It might be necessary therefore, to
      generate a hamster REG specific probe in order to further study this issue. In
      conclusion, the established model of cellophane wrapping of the pancreas provides
      a useful tool whereby the induced growth of beta-cells can be observed. The
      sequence appears to be initial stimulation of ductal cells followed by islet
      differentiation. Of the candidate genes, it appears that reg does not participate
      in the process. We will however, examine other candidate genes to elucidate the
      mechanism whereby celophane wrapping induces growth of beta-cells.

PMID- 1360191
TI  - Helicobacter pylori and peptic ulcers in rheumatoid arthritis patients receiving
      gold, sulfasalazine, and nonsteroidal anti-inflammatory drugs.
AB  - The conflicting reports on gold and Helicobacter pylori could be related to the
      use of serological tests of unproven value in NSAID patients, and to the lack of
      the appropriate control groups. More important is the fact that the endoscopic
      consequences of the possible effect of gold on H. pylori have not been
      investigated. We therefore decided to assess the prevalence of H. pylori and
      peptic ulcers in rheumatoid patients being treated with gold sodium thiomalate
      (GST) plus NSAID, sulfasalazine plus NSAID, or NSAID only. Eighty-five patients
      receiving treatment for at least 6 months were endoscoped, and H. pylori was
      studied in gastric antral biopsies by both culture and histology. Endoscopic
      abnormalities were classified into ulcers (measuring 5 mm in diameter or more)
      and erosions (smaller lesions). H. pylori (and ulcers) were found in 17 (12
      ulcers) of 31 patients on NSAID only and 21 (9 ulcers) of 27 patients on
      sulfasalazine plus NSAID, compared with nine (3 ulcers) of 27 patients receiving
      GST plus NSAID, p < 0.05, analysis of variance. Patients treated with GST and
      NSAID had the lowest prevalence of detectable H. pylori. This could explain the
      apparent reduction in the prevalence of peptic ulcers in this group and, if
      confirmed in larger randomized studies, might have therapeutic implications.

PMID- 1360192
TI  - Vector competence of California mosquitoes for California encephalitis and
      California encephalitis-like viruses.
AB  - Mosquitoes collected from coastal, inland valley, and alpine locations in
      California were evaluated for their experimental vector competence for two
      viruses in the California serogroup (Bunyaviridae:Bunyavirus). Aedes squamiger, a
      coastal salt marsh mosquito, was an efficient vector of a California encephalitis
      (CE)-like virus isolated from its habitat (89% of the pledget-fed females became
      infected and 61% transmitted virus). Aedes dorsalis, a coastal mosquito, and Ae.
      melanimon, an inland valley mosquito, were competent vectors of prototype CE
      virus (98% and 100% of the pledget-fed females became infected and 56% and 30%,
      respectively, transmitted virus). Aedes squamiger and Ae. dorsalis transmitted
      both viruses vertically to one or more of 20 of their progeny. Culiseta inornata
      was susceptible to infection with both viruses, but 5% or less transmitted virus
      perorally. Alpine mosquitoes, Ae. cataphylla, Ae. increpitus, and Ae. tahoensis,
      became infected with both CE and CE-like viruses, but 3% or less transmitted
      virus. All species of mosquitoes were more efficient vectors of both viruses
      following intrathoracic inoculation than following pledget feeding, suggesting
      the presence of mesenteronal barriers.

PMID- 1360193
TI  - Linkage and association studies with C8A and C8B RFLPs on chromosome 1.
AB  - Linkage relations for the C8A and C8B BamHI RFLPs have been investigated. A peak
      lod score of 4.52 at recombination fraction zero was obtained between the two C8
      genes. Combined with our previously obtained linkage data (Rogde et al. 1986) the
      maximum lod score is 7.53 at recombination fraction zero. The compiled C8-PGM1
      linkage data from this and the previous study gave a maximum lod score of 22.02
      at recombination fraction 0.11 (0.07-0.16) with no sex difference. A chromosome
      1p reference marker, D1S57, has been applied in this linkage study. A maximum lod
      score of 5.06 between the C8 cluster and D1S57 at theta = 0.18 (0.11-0.28) was
      recorded. The linkage analyses and triply informative families gave evidence that
      the C8 loci are situated about halfway between PGM1 and D1S57 on the short arm of
      chromosome 1. There was no evidence of allelic association between the C8A and
      C8B BamHI RFLPs in 62 unrelated haplotypes.

PMID- 1360194
TI  - Structure and chromosomal localization of the human 2',3'-cyclic nucleotide 3'
      phosphodiesterase gene.
AB  - Human brain cDNA clones for the myelin associated enzyme 2',3'-cyclic nucleotide
      3'-phosphodiesterase (CNPase) have been isolated and sequenced. The only 5'
      untranslated region (UTR) sequence found was that of a human CNPII mRNA, with no
      direct evidence for a CNPI mRNA. Human CNPase cDNAs were used to isolate genomic
      clones containing the human CNPase gene which is 9 kb long. Four exons were
      identified, separated by three introns, and the sequence of each exon and
      intron/exon boundary has been established. The polymerase chain reaction (PCR)
      was used to detect the presence of the human CNPase gene in DNA from a panel of
      rodent/human somatic cell hybrids. By this means the human CNPase gene was mapped
      to chromosome 17. In situ hybridization of a human CNPase genomic clone to
      metaphase chromosomes further localized this gene to chromosomal band 17q21.

PMID- 1360195
TI  - Cortical biopsy in Alzheimer's disease: diagnostic accuracy and neurochemical,
      neuropathological, and cognitive correlations. Intraventricular Bethanecol Study
      Group.
AB  - Neurochemical assessments were performed on biopsy samples taken from the right
      frontal lobe of patients diagnosed with Alzheimer's disease (AD), before the
      implantation of a ventricular catheter and pump assembly for the infusion of
      bethanechol chloride as an experimental therapy. The pathologically diagnosed
      patients with AD (n = 35; mean age, 67 +/- 1.5 yr) were compared with a group of
      samples from normal age-equivalent autopsied controls (n = 22; mean age, 68 +/- 2
      yr) and autopsied AD brains (n = 11; mean age, 73 +/- 2 yr). Samples were assayed
      for choline acetyltransferase (ChAT), acetylcholinesterase, binding to
      [3H]quinuclidinyl benzilate as an index of total muscarinic cholinergic binding,
      and [3H]pirenzepine binding as an index of M1 cholinergic receptor subtype
      binding. Mean levels of ChAT activity were decreased in the biopsied patients to
      36% of age-matched autopsied controls. The loss of ChAT activity correlated
      significantly with the Mini-Mental State Examination, an index of global
      cognitive function. Mean ChAT activity in autopsied AD cortex was further
      decreased compared with controls, indicating continuous decline through the
      course of the disease. Acetylcholinesterase followed a similar, less dramatic
      decline. No differences were found in [3H]quinuclidinyl benzilate binding or
      [3H]pirenzepine binding between biopsied and autopsied controls. Neuritic plaque
      counts did not correlate with either the Mini-Mental State Examination or ChAT
      activity in the biopsy specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360196
TI  - Application of a monoclonal antibody-based antigen detection enzyme-linked
      immunosorbent assay (antigen ELISA) for field diagnosis of bovine trypanosomiasis
      at Nguruman, Kenya.
AB  - A monoclonal antibody-based, enzyme immunoassay (antigen ELISA) for the detection
      of species-specific invariant antigens of Trypanosoma congolense, T. vivax or T.
      brucei in the serum of infected animals was evaluated as a means of diagnosis
      using bovine field sera from a trypanosomiasis endemic area, Nguruman, Kenya.
      Circulating trypanosome antigens were detected in 126 (96.2%) of 131 serum
      samples from animals with parasitologically confirmed diagnosis: 74.8% were
      positive for antigens of two or three trypanosome species, while 21.4% tested
      positive for one trypanosome species. When 70 sera from animals (at Nguruman),
      which had tested negative for trypanosomes by the buffy coat technique, were
      tested, 35 (50.0%) of them were shown to be antigen-ELISA positive: 24 (34.3%)
      showing infection with a single species and 11 (15.7%) with mixed infections. The
      predominant trypanosome species diagnosed in the two herds by antigen ELISA was
      T. vivax, which was detected in 133 (82.6%) of the 161 sera that tested positive
      for antigens, followed by T. congolense in 122 (75.8%) sera, with 109 (67.7%)
      showing evidence of mixed infections with two or three trypanosome species. In
      single infections, T. vivax exceeded T. congolense by a ratio of 2:1, with T.
      brucei accounting for less than 1.0%. Evidence for the specificity of the test
      was provided by analysis of field sera from 100 cattle, from a trypanosomiasis
      free area, infected with other haemoparasites (anaplasmosis, babesiosis and
      theileriosis), which all tested negative in the assay.

PMID- 1360197
TI  - Regional cerebral blood flow in monozygotic twins discordant and concordant for
      schizophrenia.
AB  - We addressed several questions regarding hypofunction of the prefrontal cortex
      ("hypofrontality") in schizophrenia by measuring regional cerebral blood flow
      during three different cognitive conditions in monozygotic twins who were
      discordant or concordant for schizophrenia or who were both normal. These
      questions included the prevalence of hypofrontality, the importance of genetic
      predisposition, and the role of long-term neuroleptic treatment. Significant
      differences between affected and unaffected discordant twins were found only
      during a task linked to the prefrontal cortex, the Wisconsin Card Sorting Test.
      During this condition, all of the twins with schizophrenia were hypofrontal
      compared with their unaffected co-twins, suggesting that, if appropriate
      cognitive conditions and control groups are used, hypofrontality can be
      demonstrated in the majority of, if not all, patients with schizophrenia. When
      unaffected co-twins of patients with schizophrenia were compared with twins who
      were both normal, no differences were observed, suggesting that nongenetic
      factors are important in the cause of the prefrontal physiologic deficit that
      appears to characterize schizophrenia. When concordant twins with a high- vs a
      low-dose lifetime history of neuroleptic treatment were compared, the twin
      receiving the higher dose was more hyperfrontal in six of eight pairs, suggesting
      that long-term neuroleptic treatment does not play a major role in
      hypofrontality.

PMID- 1360198
TI  - Frontostriatal disorder of cerebral metabolism in never-medicated schizophrenics.
AB  - We scanned 18 patients with schizophrenia who had never received neuroleptic
      medication and 20 age- and sex-matched controls by positron emission tomography
      with 18-F-fluorodeoxyglucose (fludeoxyglucose F 18) as a tracer of glucose
      metabolism. Subjects performed the Continuous Performance Test during 18-F
      fluorodeoxyglucose uptake. Scan results were converted to metabolic rates, and
      computer algorithms were used to identify cortical regions. Previous reports of
      relative hypofrontality in schizophrenia were confirmed, indicating that this
      finding is not an artifact of previous treatment. Significantly reduced ratios of
      inferior and medial frontal regions to occipital cortex were found, together with
      diminished metabolism in the basal ganglia. This suggests the presence of a
      combined frontostriatal dysfunction in schizophrenia.

PMID- 1360199
TI  - Hypofrontality in neuroleptic-naive patients and in patients with chronic
      schizophrenia. Assessment with xenon 133 single-photon emission computed
      tomography and the Tower of London.
AB  - The "hypofrontality hypothesis" has been supported by many neuroimaging studies,
      but not all, perhaps because of heterogeneity of samples. The present study
      examined three different samples that permitted assessment of a variety of
      confounders, such as effects of long-term treatment, chronicity of illness, and
      presenting phenomenology: (1) 13 neuroleptic-naive schizophrenic patients, (2) 23
      nonnaive schizophrenic patients who had been relatively chronically ill but were
      medication free for at least 3 weeks, and (3) 15 healthy normal volunteers.
      Regional cerebral blood flow was measured using single-photon emission computed
      tomography with xenon 133 as the tracer. The control condition consisted of
      looking at undulating colored shapes on a video monitor, while the experimental
      task was the Tower of London. We observed the Tower of London to be a relatively
      specific stimulant of the left mesial frontal cortex (probably including parts of
      the cingulate gyrus) in healthy normal volunteers. Both the neuroleptic-naive and
      the nonnaive patients lacked this area of activation, as well as a related one in
      the right parietal cortex (representing the circuitry specifically activated by
      the Tower of London). Decreased activation occurred only in the patients with
      high scores for negative symptoms. These results suggest that hypofrontality is
      related to negative symptoms and is not a long-term effect of neuroleptic
      treatment or of chronicity of illness.

PMID- 1360200
TI  - Negative symptoms and hypofrontality in chronic schizophrenia.
AB  - Frontal lobe dysfunction is widely suspected to underlie negative symptoms of
      schizophrenia. This hypothesis is based largely on long-standing observations of
      the similarities between the effects of frontal lobe lesions and negative
      symptoms. However, there is little direct evidence specifically for such an
      association in schizophrenic patients. We measured the relationship between
      decreased relative prefrontal cortex glucose metabolism (hypofrontality) using
      positron emission tomography and evaluated the severity of negative symptoms in
      20 chronic schizophrenics who underwent scanning while not receiving neuroleptic
      drugs. We found a close relationship between negative symptoms and prefrontal
      hypometabolism, particularly in the right dorsolateral convexity. This
      association was regionally specific. Furthermore, there was no evidence that this
      relationship was an artifact of age, cerebral atrophy, or severity of positive
      symptoms.

PMID- 1360201
TI  - Schizophrenia, genetic retrenchment, and epidemiologic renaissance. The Sixth
      Biennial Winter Workshop on Schizophrenia, Badgastein, Austria, January 26
      February 1, 1992.
AB  - A distinctive feature of these workshops, in addition to those noted in the
      introductory overview, is the selection of a relatively isolated location for a 1
      week period. This, together with a rich and varied program and an ethos of
      informality, encourages participants to discuss not only the work presented but
      also their unpublished work and their intuitions based on preliminary data and
      analyses. Such an interchange is of inestimable value to the schizophrenia
      research community. In scientific terms, a panel of concluding discussants (Drs
      Kendell, Torrey, and Waddington) were in some measure of agreement that genetics,
      particularly molecular genetics, appears to be experiencing a period of
      retrenchment, while epidemiology is experiencing something of a renaissance.
      Maternal influenza was a prominent theme, although the data were far from
      consistent. It was argued by Dr Wessely that risk for schizophrenia putatively
      attributable to maternal influenza might be 5% to 10% of all cases, indicating a
      modest effect. Eclectically, Dr Kendell believed the effect to be "real" but
      slight and fragile, it being sought against large aggregates that almost
      inevitably result in differing findings from differing countries or from
      different data bases within a given country. Gender differences were also among
      the more prominent themes, not just in an epidemiologic context but also in a
      variety of other studies. This points anew to disturbances in schizophrenia of
      factors that regulate, or are intimately associated with, sexual dimorphism in
      brain development. Abnormalities in cerebral asymmetry continue to pervade a
      variety of research findings and point further to neurodevelopmental
      anomalies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360202
TI  - Sensory testing in human immunodeficiency virus type 1-infected men. HIV
      Neurobehavioral Research Center Group.
AB  - Patients with acquired immunodeficiency syndrome frequently suffer peripheral
      neuropathy. We investigated its prevalence and relationship to clinical stage of
      human immunodeficiency virus (HIV) infection using quantitative sensory testing
      and nerve conduction testing. Vibratory threshold was determined in the right
      great toe and index finger of 179 men seropositive for HIV (28 with acquired
      immunodeficiency syndrome [AIDS] or AIDS-related complex [ARC], 151 asymptomatic)
      and 32 HIV-seronegative controls. None had clinical peripheral neuropathy.
      Abnormal threshold was control mean plus 2.5 SDs. In the toe, 10 (36%) of 28
      subjects with AIDS or ARC had abnormal vibratory thresholds, compared with seven
      (5%) of 151 asymptomatic seropositive subjects and none of 32 controls. A
      subgroup of 168 seropositive subjects underwent nerve conduction testing.
      Abnormality rates were similar, but abnormalities of nerve conduction coincided
      with quantitative sensory testing abnormalities in only half the cases. Mean (+/
      SD) vibratory threshold was significantly greater in subjects with AIDS or ARC
      (3.00 +/- 0.51 vibratory units) than in asymptomatic subjects (1.56 +/- 0.27
      vibratory units) and controls (1.63 +/- 0.54 vibratory units). Finger abnormality
      rates did not differ, although subjects with AIDS or ARC had greater mean
      vibratory threshold. Subclinical peripheral neuropathy is thus related to stage
      of HIV infection and is present by quantitative sensory testing in 36% of
      patients with AIDS or ARC.

PMID- 1360204
TI  - Cardiology at the Coast. International Symposium. Festschrift in honour of
      Professor David Wilcken. New South Wales, 18-20 March 1992.

PMID- 1360203
TI  - Restriction enzyme analysis of Norrie disease pedigrees.
AB  - Carrier detection and prenatal diagnosis of Norrie disease (ND) were performed
      using the polymorphic L1.28, OTC, and 58-1 probes. L1.28 was polymorphic in 3 of
      the 5 ND families tested and informative in 2 families (40%). Probe 58-1 and OTC
      were informative in one of 3 families (33%) and in both of the 2 families (100%)
      tested, respectively. The major allele frequency was 73% in L1.28 (DXS7), 89% in
      58-1 (DXS14), and 50% in OTC in our patient population. One of 5 families studies
      showed a recombination between probes (L1.28 and OTC) and the ND gene locus
      placing the ND locus proximal to L1.28 and OTC.

PMID- 1360205
TI  - Escherichia coli gamma-glutamyltranspeptidase mutants deficient in processing to
      subunits.
AB  - Arginyl residues 513 and 571 of Escherichia coli K-12 gamma-glutamyl
      transpeptidase (EC 2.3.2.2) were substituted with alanyl and glycyl residues,
      respectively, by oligonucleotide-directed in vitro mutagenesis. Both mutants were
      devoid of the enzymatic activity. On Western blot analysis, we found that both
      mutants accumulated a gamma-glutamyltranspeptidase precursor which was not
      processed into large and small subunits in the periplasmic space of Escherichia
      coli.

PMID- 1360206
TI  - Stable expression of natriuretic peptide receptors: effects of HS-142-1, a non
      peptide ANP antagonist.
AB  - We established clonal cell lines stably expressing each of two subtypes of
      membrane bound guanylate cyclases (GC-A and GC-B), which are known as natriuretic
      peptide receptors. Using these cell lines, we showed that GC-A is an ANP/BNP
      receptor, whereas GC-B is a specific receptor for CNP. Effects of HS-142-1, a
      novel non-peptide ANP antagonist, on GC-A and GC-B were examined by using these
      cells. In cells expressing either GC-A or GC-B, HS-142-1 inhibited cGMP
      production elicited by ANP or CNP with IC50 values of 1.8 micrograms/ml and 1.5
      micrograms/ml, respectively, and also competitively blocked specific binding of
      the natriuretic peptides with IC50 values of 2.2 micrograms/ml and 3.3
      micrograms/ml, respectively. These results indicate that HS-142-1 is a potent
      antagonist of CNP as well as ANP. We also showed that CNP suppressed the growth
      of cells expressing GC-B by 22% and that HS-142-1 blocked the antiproliferative
      action of CNP.

PMID- 1360207
TI  - The MDR1 gene product, P-glycoprotein, mediates the transport of the cardiac
      glycoside, digoxin.
AB  - Digoxin, a widely used cardiac glycoside with a low therapeutic index, is known
      to interact with a large and diverse group of co-administered drugs, frequently
      leading to toxic accumulation of the glycoside. Establishing the mechanism(s) of
      these interactions, therefore, has potential clinical significance. The present
      studies implicate P-glycoprotein, the MDR1 gene product overexpressed in
      multidrug resistant cells, as the apical membrane protein responsible for the
      renal secretion of digoxin and provide an explanation for the occurrence of
      digoxin toxicity in the presence of certain co-administered medications. Since
      digoxin is considered a prototype for endogenous digitalis-like glycosides, the
      results also allow for speculation that endogenous digitalis-like glycosides may
      be the natural substrates for P-gp.

PMID- 1360208
TI  - Production of catecholamines in the human epidermis.
AB  - Cell-free extracts from human full thickness skin (i.e., epidermis and dermis),
      suction blister roofs (i.e., epidermis) and from human keratinocytes express
      biopterin-dependent tyrosine hydroxylase a well as phenylethanolamine-N-methyl
      transferase, both representing key enzymes for the biosynthesis of epinephrine.
      These enzyme activities could not be detected in cell extracts from human
      melanocytes and human fibroblasts. Since keratinocytes in the human epidermis,
      and in cell cultures, express a high density of beta-2-adrenoceptors, and this
      signal transduction system regulates intracellular calcium homeostasis, it can be
      concluded that epinephrine production in the epidermis activates calcium
      transport via the beta-2-adrenoceptor system. Our results show for the first time
      that the human epidermis has the capacity to independently produce epinephrine.

PMID- 1360209
TI  - Multidrug resistant HOB1 lymphoma cells express P-glycoprotein that does not play
      the major role in the development of drug resistance to adriamycin.
AB  - Two cell lines resistant to 0.1 microM vincristine (VCR) and 2.0 microM
      adriamycin (ADR), respectively, (designated HOB1/VCR0.1 and HOB1/ADR2.0) were
      established from a human immunoblastic B lymphoma cell line. These cell lines
      showed the typical MDR phenotype with overexpression of P-glycoprotein and
      decreased [3H]VCR accumulation. The retention amounts of intracellular [3H]VCR in
      these two cell lines could be augmented by verapamil. However, in spite of the
      overproduction of P-glycoprotein, both HOB1/VCR1.0 and HOB1/ADR2.0 cells did not
      exhibit decreased accumulation of intracellular [14C]ADR. And the retention of
      [14C]ADR was not affected by verapamil. Our data support that P-glycoprotein is a
      drug transporter more important for the development of drug resistance to VCR
      than to ADR.

PMID- 1360210
TI  - Effects of a new triazinoaminopiperidine derivative on adriamycin accumulation
      and retention in cells displaying P-glycoprotein-mediated multidrug resistance.
AB  - A new triazinoaminopiperidine derivative, Servier 9788 (S9788), was investigated
      for its ability to increase Adriamycin (ADR) accumulation and retention in two
      rodent (P388/ADR and DC-3F/AD) and three human (KB-A1, K562/R and COLO 320DM)
      cell lines displaying the P-glycoprotein (P-gp)-mediated multidrug resistance
      (MDR) phenotype. Depending on the cell line S9788 was shown to be two to five
      times more active and five to 15 times more potent than Verapamil (VRP) in
      increasing ADR accumulation in resistant cells. ADR retention in KB-A1 cells
      maintained in a concentration of 10 microM S9788 was twice that in VRP-treated
      cells, and similar to that measured in the untreated sensitive KB-3-1 cells.
      Although 5 microM S9788 and 50 microM VRP gave the same values of ADR uptake in
      KB-A1 cells, S9788 was shown to induce a greater ADR retention following cell
      wash and post-incubation in resistance modifier- and ADR-free medium. Taking into
      account that S9788 had no effects on ADR accumulation and retention in sensitive
      KB-3-1 cells, it can be suggested that S9788 inhibits specifically the P-gp
      dependent ADR efflux, and in a manner less reversible than that observed with
      VRP. Moreover, [3H]azidopine photolabeling of P-gp, in P388/ADR plasma membranes,
      was completely inhibited by 100 microM S9788. Although S9788, as VRP, had no
      effect on the cell cycle of P388 cells, 5 microM S9788 increased 700-fold the
      efficacy of ADR to block P388/ADR cells in the G2+M phase of the cell cycle.
      Together, these results show that the sensitization, by S9788, of cell lines
      resistant to ADR is mainly due to an increase in ADR accumulation and retention,
      leading to an increase in the number of resistant cells blocked in the G2+M
      phase.

PMID- 1360211
TI  - Inhibition of aminopeptidases N, A and W. A re-evaluation of the actions of
      bestatin and inhibitors of angiotensin converting enzyme.
AB  - The effects of a range of metallopeptidase inhibitors on the activities of the
      porcine kidney cell surface zinc aminopeptidases, aminopeptidase A (AP-A; EC
      3.4.11.2), aminopeptidase N (AP-N; EC 3.4.11.7) and aminopeptidase W (AP-W; EC
      3.4.11.16), have been directly compared. Amastatin and probestin were effective
      against all three aminopeptidases, with the concentration of inhibitor required
      to cause 50% inhibition (I50) in the low micromolar range (I50 = 1.5-20 microM),
      except for probestin with AP-N which displayed an I50 of 50 nM. Actinonin failed
      to inhibit significantly either AP-A or AP-W, and thus can be considered a
      relatively selective inhibitor (I50 = 2.0 microM) of AP-N. In contrast, bestatin
      was a relatively poor inhibitor of AP-N (I50 = 89 microM) and failed to inhibit
      AP-A, but was more potent towards AP-W (I50 = 7.9 microM). Thus, some of the
      observed chemotherapeutic actions of bestatin may be due to inhibition of cell
      surface AP-W. A number of other metallopeptidase inhibitors, including inhibitors
      of endopeptidase-24.11 (EC 3.4.24.11) and membrane dipeptidase (EC 3.4.13.11),
      and the carboxylalkyl and phosphoryl inhibitors of angiotensin converting enzyme
      (EC 3.4.15.1) failed to inhibit significantly AP-A, AP-N or AP-W. However, AP-W
      was inhibited with I50 values in the micromolar range by the sulphydryl
      converting enzyme inhibitors rentiapril (I50 = 1.6 microM), zofenoprilat (I50 =
      7.0 microM) and YS 980 (I50 = 17.7 microM). Neither AP-A nor AP-N were affected
      by these sulphydryl compounds. Inhibition of AP-W may account for some of the
      side effects noted with the clinical use of the sulphydryl converting enzyme
      inhibitors. The availability of compounds which are totally selective for AP-W
      over any of the other mammalian cell surface zinc aminopeptidases may aid in
      identifying endogenous substrates, and thus physiological or pathophysiological
      role(s) of AP-W.

PMID- 1360212
TI  - Drug interactions in intestinal transport of folic acid and methotrexate. Further
      evidence for the heterogeneity of folate transport in the human small intestine.
AB  - The effect of sulfasalazine and olsalazine on the transport of [3H]folic acid and
      of [3H]methotrexate (MTX) was investigated in organ-cultured endoscopic biopsy
      specimens of small intestinal mucosa from normal subjects. Biopsy specimens
      obtained from patients undergoing routine diagnostic upper gastrointestinal
      endoscopy were organ-cultured at pH 5.5 and the effect of these two drugs on the
      initial rate of uptake of the two folates was determined. Both drugs inhibited
      the transport of [3H]folic acid with similar Ki values (1.38 and 1.32 mM for
      sulfasalazine and olsalazine, respectively). However, the uptake of [3H]MTX was
      only partially inhibited by sulfasalazine and was unaffected by olsalazine.
      Sulfasalazine inhibited 26.2% of the total flux of MTX, in close agreement with
      the fraction of MTX flux that has been shown previously to be inhibited by folic
      acid. These data corroborate previous findings of heterogeneity of transport of
      MTX in the mucosa of the human small intestine.

PMID- 1360213
TI  - Characterization of adriamycin-resistant and radiation-sensitive Chinese hamster
      cell lines.
AB  - A series of cell lines derived from Chinese hamster V79 cells by selection in
      increasing concentrations of Adriamycin (ADRM) was developed to study the
      mechanisms of drug resistance and its relationship to radiation response.
      Survival studies revealed that selection in increasingly higher concentrations of
      ADRM positively correlated with increased cellular drug resistance. Increased
      cellular resistance correlated positively with amplification of the hamster
      multidrug-resistance gene (pgp 1) as detected with dot blot analysis using the
      pCHP1 probe. Southern blot analysis of restriction endonuclease digested DNA (Eco
      RI, Hind III, Pst I, or Bam HI) showed that (1) some fragments were
      preferentially amplified compared to others in the ADRM-resistant lines; and (2)
      no major gene rearrangement appeared to have occurred during the selection for
      greater ADRM resistance. Levels of pgp 1 gene expression assayed with dot blot
      and Northern analysis showed a parallel increase of mRNA with gene amplification
      and increased ADRM resistance. The amounts of the pgp 1 gene product, P
      glycoprotein (P-gp), in the cell membrane of the ADRM-resistant cells correlated
      with the amount of gene amplification/expression. However, levels of P-gp only
      correlated with degree of drug resistance as measured by cell survival in earlier
      selection stages (77A and LZ-3). In later selection stages (LZ-8 and LZ-24),
      higher levels of ADRM resistance were achieved but levels of P-gp did not
      increase beyond approximately 20% of plasma membrane proteins. These results
      suggest that (1) the LZ cell plasma membrane may have a physical limit as to the
      amount of P-gp it can accommodate and/or there is a cellular mechanism for
      regulating the amount of P-gp in the plasma membrane, and (2) additional
      resistance mechanisms are present in LZ-8 and LZ-24 cells. Microscopic
      observations of intracellular drug distribution in these cell lines revealed that
      (1) ADRM appeared to be sequestered in cytoplasmic vesicles, and (2) the amount
      of sequestration (number of vesicles) exhibited correlated with the degree of
      drug resistance attained by the cell lines. These results suggest that drug
      sequestration is another mechanism of resistance in LZ cells in addition to P-gp
      mediated drug efflux.

PMID- 1360214
TI  - An enhanced ability for transforming adriamycin into a noncytotoxic form in a
      multidrug-resistant cell line (LZ-8).
AB  - Multidrug-resistant LZ-8 cells are 9000-fold more resistant to Adriamycin (ADRM)
      exposure than wild-type V79 cells. To understand more about the mechanisms
      producing such high level resistance, we tested whether LZ-8 cells inactivate
      ADRM toxicity to a greater extent than wild-type V79 cells. ADRM was recovered
      from (1) culture media of wild-type V79 and ADRM-resistant LZ-8 cells; (2) V79
      and LZ-8 cells; and (3) LZ-8 cell plasma membrane, and the cytotoxicity was
      determined by treating V79 cells for 1 hr with a known concentration of the
      recovered ADRM. ADRM obtained from LZ-8 cells or its culture medium exhibited
      less cytotoxicity than that recovered from V79 cells or its culture medium. ADRM
      extracted from LZ-8 cell plasma membrane was noncytotoxic. HPLC analysis revealed
      that the extracted ADRM was structurally changed compared to stock ADRM. The
      retention time in the column was 7 min for stock ADRM, and 23 min for the
      recovered ADRM. Thus, LZ-8 cells have an increased ability to transform ADRM into
      a noncytotoxic form compared to wild-type V79 cells. This transformation involves
      structural conversion into a previously unidentified ADRM metabolite. The greatly
      increased survival of LZ-8 cells compared to V79 cells after ADRM treatment is
      due to at least two mechanisms: (1) an enhanced ability to inactivate the
      cytotoxicity of ADRM, and (2) increased drug efflux resulting from the
      amplification and overexpression of the pgp 1 gene in these cells. Our results
      suggest the possibility that P-glycoprotein participates in drug
      binding/inactivation in addition to serving as a drug efflux pump.

PMID- 1360215
TI  - Alcohol-induced macrocytosis and blood pressure.
AB  - The effect of alcohol on blood pressure was studied prospectively in consecutive
      general practice patients with macrocytosis (MCV greater than or equal to 100
      fl). The patients were separated into misuser and non-misuser groups on the basis
      of the Malmo modified Michigan Alcoholism Screening Test. There was no
      significant difference in the prevalence of antihypertensive medication between
      the misuser and non-misuser groups. When patients using antihypertensive
      medication were excluded and the groups were age-adjusted, male misusers (n = 95)
      compared to control patients (n = 22) had significantly higher diastolic (88 mmHg
      and 81 mmHg, respectively, P = 0.001) and systolic (146 mmHg and 137 mmHg,
      respectively, P less than 0.001) blood pressure values. Female misusers (n = 24),
      as compared to female non-misusers (n = 59) had significantly higher diastolic
      (83 mmHg and 82 mmHg, respectively, P = 0.04) but not systolic blood pressure
      values. Thus, alcohol seems to have a pressor effect predominantly among men. As
      72% of men with macrocytosis were alcohol misusers and 41% of them either had
      elevated systolic or diastolic blood pressure, all patients with macrocytosis
      should be asked about their alcohol consumption and at least the males should
      have blood pressure measured.

PMID- 1360216
TI  - The A14 position of insulin tolerates considerable structural alterations with
      modest effects on the biological behavior of the hormone.
AB  - As part of our aim to investigate the contribution of the tyrosine residue found
      in the 14 position of the A-chain to the biological activity of insulin, we have
      synthesized six insulin analogues in which the A14 Tyr has been substituted by a
      variety of amino acid residues. We have selected three hydrophilic and charged
      residues--glutamic acid, histidine, and lysine--as well as three hydrophobic
      residues--cycloleucine, cyclohexylalanine, and naphthyl-(1)-alanine--to replace
      the A14 Tyr. All six analogues exhibit full agonist activity, reaching the same
      maximum stimulation of lipogenesis as is achieved with porcine insulin. The
      potency for five of the six analogues, [A14 Glu]-, [A14 His]-, [A14 Lys]-, [A14
      cycloleucine]-, and [A14 naphthyl-(1)-alanine]-insulins in receptor binding
      assays ranges from 40-71% and in stimulation of lipogenesis ranges from 35-120%
      relative to porcine insulin. In contrast, the potency of the sixth analogue, [A14
      cyclohexylalanine]insulin, in both types of assays is less than 1% of the natural
      hormone. The retention time on reversed-phase high-performance liquid
      chromatography for the first five analogues is similar to that of bovine insulin,
      whereas for the sixth analogue, [A14 cyclohexylalanine]insulin, it is
      approximately 11 min longer than that of the natural hormone. This suggests a
      profound change in conformation of the latter analogue. Apparently, the A14
      position of insulin can tolerate a wide latitude of structural alterations
      without substantial decrease in potency. This suggests that the A14 position does
      not participate directly in insulin receptor interaction. Only when a
      substitution which has the potential to disrupt the conformation of the molecule
      is made at this position, is the affinity for the receptor, and hence the
      biological potency, greatly reduced.

PMID- 1360217
TI  - Immunocytochemical localization of cyclin/proliferating cell nuclear antigen
      (PCNA) in fertilized eggs of mice.
AB  - Immunolocalization of cyclin/PCNA (proliferating cell nuclear antigen) was
      performed with monoclonal antibody using immunogold methods on ultrathin
      cryosections of fertilized mouse eggs. Immunolabeling in pronuclei was checked
      20, 22, 24 and 26 h after HCG injection. A relation between onset of pronuclei
      migration (early S-phase) and appearance of colloidal particle clusters was
      found. Afterwards, (mid S-phase) the increase of labelling and the localization
      of cyclin/PCNA were found throughout the pronuclei, except in the nucleolar
      bodies. Lower labelling appeared at the time of close reciprocal pronuclei
      contact (late S-phase). It is concluded that bulk and distribution of cyclin/PCNA
      in pronuclei is closely related to the progression of first interphase after
      fertilization.

PMID- 1360218
TI  - Plasma and tissue levels of digestive regulatory peptides during postnatal
      development and weaning in the calf.
AB  - Changes in the concentrations of cholecystokinin, gastric inhibitory peptide,
      gastrin, motilin, pancreatic polypeptide, secretin, somatostatin, and vasoactive
      intestinal peptide in calf plasma and antral, duodenal and/or pancreatic tissues
      were assessed by radioimmunoassay during postnatal development and after weaning
      in 50 male Holstein-Friesian calves (randomly distributed into 10 groups of 5
      animals each). The calves in the first group were killed at birth while those in
      6 other groups were colostrum-fed for 2 days and then milk-fed until 7, 28, 56,
      70 or 119 days of age. Those in the remaining 3 groups were given the same diets
      until day 28, were then weaned between day 29-56, and slaughtered on days 56, 70
      or 119. In milk-fed animals, changes in plasma and tissue concentrations of
      almost all digestive regulatory peptides were observed during the 1st month of
      postnatal life, especially at day 2. Weaning was accompanied by variations in the
      plasma concentrations of somatostatin, secretin, gastrin, pancreatic polypeptide
      and gastric inhibitory peptide but not by any apparent change in peptide tissue
      concentrations (except VIP in the duodenum). Thus, the variations in tissue
      concentrations are primarily age-related, while plasma concentrations were
      modified by age and weaning.

PMID- 1360219
TI  - Dolichol and Other Lipids Related to Glycoconjugate Metabolism. Satellite to the
      11th International Symposium on Glycoconjugates. Kimberly, Ontario, Canada, June
      26-29, 1991.

PMID- 1360220
TI  - Studies on the activation by dolichol-P-mannose of the biosynthesis of GlcNAc-P-P
      dolichol and the topography of the GlcNAc-transferases concerned with the
      synthesis of GlcNAc-P-P-dolichol and (GlcNAc)2-P-P-dolichol: a review.
AB  - A review is presented of research carried out in this laboratory on two aspects
      of the dolichol pathway that may have regulatory influences on these events. (i)
      The validity of the phenomenon of the activation of the biosynthesis of GlcNAc-P
      P-dolichol and (GlcNAc)2-P-P-dolichol by dolichol-P-mannose is supported by
      experiments carried out on the Thy-1-negative mouse lymphoma cell. While this
      cell cannot synthesize the activating compound, this capacity was retained and
      revealed upon the addition of exogenous dolichol-P-mannose. (ii) The
      topographical orientation of the GlcNAc-transferases that catalyze the
      biosynthesis of GlcNAc-P-P-dolichol and (GlcNAc)2-P-P-dolichol was investigated
      in microsomes from the liver of the embryonic chick using dolichol phosphate
      liposomes as an exogenous substrate. The formation of GlcNAc-P-P-dolichol and
      (GlcNAc)2-P-P-dolichol was inhibited by trypsinization under conditions where the
      native orientation of the microsome was maintained, as indicated by the latency
      of mannose-6-phosphatase. Both GlcNAc-lipids were detected on free liposomes
      after incubation with intact microsomes, and in the same proportions as found on
      the microsome. From these and other studies, evidence was obtained indicating the
      cytoplasmic orientation of the GlcNAc-transferases that catalyze the synthesis of
      the first two intermediates of the dolichol pathway.

PMID- 1360221
TI  - Treatment of traumatic dental injuries in children.
AB  - The major emphasis of this review should rest on articles written within the past
      12 months. Many of these papers comprise comprehensive surveys of treatment of
      various aspects of dental trauma in the primary and permanent dentition, as well
      as epidemiological studies. There have also been some very good experimental
      studies which have attempted to standardize luxation injuries as well as tooth
      replantation in order to study pulpal and periodontal healing in reproducible
      animal models. However, it can be seen from the reference list that one year's
      production in dental traumatology would not suffice to cover the scope of the
      treatment needs nor to adequately orient the reader on the progress made with
      respect to our present knowledge of wound healing following injury and the most
      recent developments in the restoration of the traumatized dentition. To present
      an overall view of the philosophy which has evolved concerning wound healing in
      the dental pulp and periodontium following injury as well as innovations in the
      treatment of acute dental trauma, this review must of necessity delve back into
      the mid-80's and probe forward into publications which are on the way in 1991. In
      1984, in Dallas, Texas, the American Association of Endodontists' Endowment and
      Memorial Foundation convened the first International Conference on Oral Trauma.
      In 1989, in Stockholm, Sweden, this was followed up with the second International
      Conference on Dental Trauma. The one-day program summarized the state of the art
      of dental traumatology with respect to various aspects of epidemiology,
      diagnosis, treatment and prevention as well as the biological principles which
      form a basis for our present knowledge about healing and healing complications in
      the pulp and periodontium after traumatic dental injuries. The proceedings from
      this conference have been compiled in a newly published volume. Where applicable,
      these presentations have been cited as current reviews. It could also be
      mentioned that at the conclusion of the second conference, in recognition of the
      need to promote research and propagate knowledge in the area of dental
      traumatology, the International Association of Dental Trauma (IADT) was founded.
      The third International Conference on Dental Trauma was convened in Copenhagen,
      Denmark, June 1991. The major theme was restoration of the traumatized dentition.
      Proceedings from this conference are to be published. However, new information
      from that program is also cited in the following where applicable. Finally, the
      second Charlotte Conference on Pathobiology of the Dentin/Pulp Complex was held
      in Charlotte, North Carolina in May 1991.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1360222
TI  - Inadequate internal mammary artery graft as a cause of postoperative ischemia:
      incidence, diagnosis and management.
AB  - Inadequate left internal mammary artery (LIMA) graft to the left anterior
      descending artery (LAD) was encountered in 10 of 3,076 patients between 1984 and
      July 1990. The mean number of bypass grafts was 2.9 per patient. All patients
      with inadequate LIMA grafts were stable preoperatively with normal to moderately
      reduced left ventricular function. No technical difficulties were encountered
      during surgery. All patients were weaned off cardiopulmonary bypass with minimal
      or no inotropic support. Each patient developed myocardial ischemia of the LAD
      territory and/or circulatory collapse or recurrent ventricular dysrhythmia during
      the first 24 h postoperatively. Six patients, who were immediately re-operated on
      and had an additional saphenous graft to the LAD, recovered with no infarction
      and good functional results. Four patients, who were medically treated, developed
      myocardial infarction. In cases of refractory circulatory collapse and/or
      ventricular dysrhythmia, inadequate LIMA flow should be suspected. We recommend
      urgent re-operation with additional saphenous vein graft to the LAD.

PMID- 1360224
TI  - Treatment of a dental phobic with pronounced aversion to rubber gloves.
AB  - This case illustrates where excessive dental stress on the swallowing reflex
      caused retching then nausea and eventually dental phobia. Swallowing relaxation
      enabled normal variable function to be quickly restored, which allowed the phobia
      to be brought under control.

PMID- 1360223
TI  - Physiology and Pathophysiology of Eicosanoids. Proceedings of a Symposium.
      Kloster Knechtsteden, January 20-23, 1992.

PMID- 1360225
TI  - Heads and tales: recent advances in craniofacial development.
AB  - In the last few years, our understanding of the complex series of events
      governing craniofacial morphogenesis has significantly increased. A variety of
      experimental approaches, such as cell lineage marking, monoclonal antibodies,
      organ culture and recombinant DNA techniques, have been fundamental to this
      progress. The neural crest contribution to the head and face of the embryo has
      been mapped, the significance and mechanisms of epithelial-mesenchymal
      interactions are better understood, and a number of regulatory molecules, which
      are likely to be causally involved in mediating the morphogenesis of the
      different craniofacial regions, have been identified. Although the information
      presently available on the molecules involved is far from complete, and the
      experimental strategies need further refinement, the existence of specific
      combinatorial gene-codes (ie the homeobox-containing gene code) has become
      evident. These findings are proving invaluable to our understanding of the
      mechanisms underlying craniofacial development, and of certain syndromes
      affecting craniofacial structures in humans.

PMID- 1360226
TI  - Beyond the mega-trial: certainty and uncertainty.

PMID- 1360228
TI  - Genes, oncogenes, and hormones. Dedicated to William L. McGuire.

PMID- 1360227
TI  - Inflammation of the subacromial bursa in chronic shoulder pain.
AB  - Subacromial bursal tissue was studied in 12 patients operated on for painful (10
      patients with constant pain and 2 patients with pain on motion) rotator cuff
      tendinitis/impingement syndrome. The Neer acromioplasty technique was used. Six
      patients had moderate inflammatory changes and one had a slight inflammation. In
      three of the five remaining patients, the subacromial bursa did not show any
      signs of inflammatory involvement, but patients experienced pain at rest and at
      night, reflecting clinical inflammation in tissues other than the bursa. The two
      patients with pain only on strain did not show inflammation of the bursa.
      Immunohistochemical typing of the bursal tissue disclosed a typical chronic
      mononuclear cell infiltrate consisting mainly of CD2-positive T lymphocytes (50
      80% of all inflammatory cells), accompanied by less frequent CD11b (C3bi
      receptor)-positive monocyte/macrophages (10-40%). The relative paucity of
      plasmablasts/plasma cells expressing PCA-1 suggests this to be an inflammatory
      rather than an immune response. Active involvement of some of the local cells is
      suggested to be the source of algogenic and hyperalgesic substances contributing
      to pain in chronic shoulder pain syndromes.

PMID- 1360229
TI  - Mechanisms involving an expanding erbB/EGF receptor family of tyrosine kinases in
      human neoplasia.

PMID- 1360230
TI  - c-erbB2 amplification and overexpression in human tumors.
AB  - There is no evidence for activation of c-erbB2 by mutation in human cancer. Gene
      rearrangements are observed at low frequency, but there are a proportion of human
      cancers that are associated with c-erbB2 gene amplification and membrane protein
      overexpression. The human cancers so affected are adenocarcinomas of the breast,
      ovary, stomach, and bladder, with up to 20% of primary lesions exhibiting either
      increased gene copy number and/or excess membrane staining. The c-erbB2 protein
      on these tumors could be used as a therapeutic target, as in monoclonal antibody
      targetted therapy already being assessed in c-erbB2 positive breast cancer. Other
      possible therapeutic strategies include the development of tyrosine kinase
      inhibitors or ligand antagonists.

PMID- 1360231
TI  - Clinical significance of erbB2 protein overexpression.

PMID- 1360232
TI  - Anti-p185HER2 monoclonal antibodies: biological properties and potential for
      immunotherapy.

PMID- 1360233
TI  - Role of type IV collagenases in human breast cancer.

PMID- 1360235
TI  - Involvement of protein kinase C in the growth regulation of human breast cancer
      cells.

PMID- 1360234
TI  - A chimeric EGFR/neu receptor in studies of neu function.

PMID- 1360236
TI  - Tyrosine kinase receptor--nuclear protooncogene interactions in breast cancer.
AB  - In summary, evidence is beginning to accumulate in support of a major role for
      tyrosine kinase receptors (and their activating growth factors) and steroid
      hormones and their receptors in normal development and differentiation of the
      mammary gland. A point of intersection of their mechanisms of action in growth
      control appears to be the induction of nuclear protooncogenes such as c-myc. When
      c-myc is amplified, as it is in many breast cancers, EGF and FGF receptor
      tyrosine kinase action becomes transforming, not simply mitogenic. A source of
      the transforming factors could be either stromal or epithelial. This mechanism
      could function early in the progression of breast cancer. c-erbB-2 and EGF
      receptor overexpression and amplification, when they occur, appear to render
      tumors even more malignant and of especially poor prognosis. These mechanisms
      could function late in the progression of breast cancer. Transgenic mouse studies
      have begun to echo these themes. They have established that a growth factor (TGF
      alpha) and its receptor (EGF receptor), which appear to be important in normal
      mouse and human proliferation and gland development, and a protooncogene (c-myc),
      commonly amplified and overexpressed in human and mouse breast cancer, can each
      contribute to mammary carcinogenesis. The mechanisms of the two are likely to be
      distinct. myc is likely to be acting as a tumor initiator in combination with
      normal proliferative factors, whereas TGF-alpha is likely to be acting as a
      hyperproliferative (promotional) factor in combination with a normal background
      of mutational events. The role of unmutated but amplified erbB-2 in the
      transgenic mouse is not yet known.

PMID- 1360237
TI  - Characterization and regulation of estrogen and progesterone receptors in breast
      cancer.

PMID- 1360239
TI  - Estrogen and progesterone receptor structure and action in breast cancer cells.

PMID- 1360240
TI  - Progesterone receptors in breast cancer.

PMID- 1360238
TI  - Prognostic factors in axillary node-negative breast cancer.

PMID- 1360241
TI  - Casein gene expression: from transfection to transgenics.

PMID- 1360243
TI  - Stromal-epithelial interactions in breast cancer.

PMID- 1360242
TI  - The whey acidic protein.

PMID- 1360244
TI  - Suppressor genes in breast cancer: an overview.
AB  - It is apparent that multiple genetic events occur in the development and
      progression of breast cancer. From the limited data available, no consistent
      temporal pattern of mutational events is required. This conclusion is consistent
      with data in colorectal carcinoma, where the number of mutational events, and not
      the order, appears to be relevant. Several authors have questioned whether the
      multiple mutational events occur independently or whether significant
      associations were evident. Cropp et al. postulated that two sets of mutational
      events occurred simultaneously in a higher degree of breast tumors than expected
      based on chance: Set 1 consisted of deletions on 11p, 17p, 18q, and int-2 and myc
      amplifications; set 2 consisted of 17q, 1p, and 3p deletions. Sato et al.,
      analyzing another tumor cohort for simultaneous mutations, noted a correlation of
      17p and 16q deletions, 13q and 17p deletions, and 17p deletion with erbB-2
      amplification. Clearly, concordant data on this issue will require the use of
      large breast tumor cohorts for a comprehensive set of probes. The reasons why
      mutations to specific genes on different chromosomes tend to occur coordinately
      is unknown, but may involve common flanking and/or intron sequences at high risk
      for certain types of mutational events. Another interesting question is the
      degree to which alterations, but not homozygous inactivation, of suppressor genes
      occur and its phenotypic consequences. In this chapter, evidence was presented
      for the amplification of a DCC allele in breast cancer and for variable RB
      protein expression in breast tumors as a consequence of allelic deletion. For
      many of the metastasis suppressor genes, a simple reduction in their expression,
      or an alteration in their expression over the normal cellular regulatory
      controls, may be sufficient to fuel the metastatic process. The data suggest a
      more complex regulation of the cancer phenotype by suppressor genes than by
      recessive inactivation alone. Why do many sporadic cancers, including breast
      cancer, appear to require alterations to multiple suppressor genes, as compared
      to diseases such as retinoblastoma, where a single suppressor gene appears to
      control the cancer phenotype? The answer to this question is unknown, but most
      theories are based on the hypothesis that suppressor genes act to control
      cellular responses to either other cells or signals in the microenvironment. In
      retinoblastoma all cells can carry a germ-line mutation. Cells carrying the RB
      mutation can interact with both the embryonic and differentiated
      microenvironments; the specific interaction of mutated cells with the embryonic
      retinal microenvironment may trigger the onset of retinoblastoma.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1360245
TI  - The role of the retinoblastoma gene in breast cancer development.
AB  - The observation that the human retinoblastoma gene is inactivated in about 20% of
      breast carcinomas indicates that it may be important in the development of these
      tumors. The fact that the loss of RB1 expression correlates with the progression
      of the disease, and especially with the inability of the cells to differentiate,
      is consistent with the clinical observation that retinoblastoma does not occur in
      children in whom the target cells have already fully differentiated. This
      suggests that the normal function of RB1 is to promote differentiation. It is
      possible that the loss of the ability of a cell to differentiate contributes to
      its ability to grow in a foreign environment (metastasis), but this hypothesis
      remains to be tested. Our observation that the overexpression of RB1 suppresses
      the growth of these tumor cells in vitro is consistent with this hypotheses.

PMID- 1360246
TI  - Mammary-derived growth inhibitor (MDGI).

PMID- 1360247
TI  - Roles for transforming growth factors-beta in the genesis, prevention, and
      treatment of breast cancer.

PMID- 1360248
TI  - Stereochemical studies of chiral H-1 antagonists of histamine: the resolution,
      chiral analysis, and biological evaluation of four antipodal pairs.
AB  - The resolution of the H-1 antihistamines chloropheniramine, dimethindene,
      carbinoxamine, and mebrophenhydramine is described. The optical purity of
      antipodal products is investigated by chiral HPLC (use of alpha 1-acid
      glycoprotein and beta-cyclodextrin columns) and NMR (spectra of beta-cyclodextrin
      inclusion complexes). Configurational relationships among the group are reviewed
      and assignments are confirmed and extended by circular dichroism evidence.
      Affinity constants of antipodal pairs for guinea pig ileum and cerebellum sites,
      determined by gut bath and binding experiments respectively, are reported
      together with some in vivo tests in man for central effects. Results are
      discussed in terms of configurational requirements for activity and variations in
      antipodal potency ratios within the group.

PMID- 1360249
TI  - Tumor assessment and response to therapy studied by magnetic resonance
      spectroscopy. Proceedings of the 17th L. H. Gray Conference. Canterbury, 13-16
      April 1992.

PMID- 1360250
TI  - AIDS conference in Amsterdam: prevalence of social problems and a possible third
      virus.

PMID- 1360251
TI  - The 2nd International Symposium on Hodgkin's Disease. Cologne, Germany, October 3
      5, 1991.

PMID- 1360252
TI  - An overview of the Second International Symposium on Hodgkin's disease.

PMID- 1360253
TI  - The Second International Symposium on Hodgkin's Disease. Workshop II: Recent
      advances in basic and clinical research.

PMID- 1360254
TI  - The Second International Symposium on Hodgkin's Disease. Workshop I: Review on
      prognostic factors.

PMID- 1360255
TI  - Single and repeated doses of the vasodilator/beta-adrenergic antagonist,
      carvedilol, block cirazoline- and isoproterenol-mediated hemodynamic responses in
      the conscious rat.
AB  - The purpose of this study was to evaluate the effects of carvedilol, a beta 1&2
      adrenergic blocker and vasodilator, on cirazoline-mediated changes in arterial
      blood pressure and isoproterenol-mediated changes in heart rate after acute and
      chronic administration. Conscious, chronically instrumented male Sprague-Dawley
      rats were injected with carvedilol (1 mg/kg, IV), prazosin (0.3 mg/kg, IV), or
      propranolol (1 mg/kg, twice daily for 8 days. After administration of the first
      dose of carvedilol on day 1, the vasopressor response to cirazoline (60 +/- 3
      mmHg predrug) and the isoproterenol-induced tachycardia (152 +/- 13 beats/min
      predrug) were blocked (e.g., 7 +/- 4 mmHg postdrug and 11 +/- 3 beats/min
      postdrug, respectively). After the administration of carvedilol on day 8, the
      cirazoline vasopressor response was 2 +/- 1 mmHg and the isoproterenol-induced
      tachycardia was 4 +/- 3 beats/min, indicating effective alpha 1- and beta
      adrenergic blockade after chronic dosing with carvedilol. Prazosin blocked the
      cirazoline-induced vasopressor response on both days 1 and 8 but had no effect on
      the isoproterenol-induced tachycardia. Propranolol blocked the isoproterenol
      induced tachycardia on both days 1 and 8 but had no effect on the cirazoline
      vasopressor response. These data indicate that only carvedilol effectively
      blocked both alpha- and beta-adrenergic hemodynamic responses and that the
      antagonism of these responses with carvedilol was not diminished after chronic
      dosing of twice-a-day treatment for 8 days.

PMID- 1360256
TI  - Combined invasive and noninvasive study of left ventricular systolic and
      diastolic function following acute administration of cicloprolol to subjects with
      normal cardiac function.
AB  - Cicloprolol is a new beta-blocking agent with high selectivity for beta 1
      receptors and high intrinsic sympathomimetic activity. We studied the acute
      hemodynamic effects of cicloprolol in nine subjects with no evidence of left
      ventricular dysfunction who underwent cardiac catheterization for the evaluation
      of chest pain. All patients had normal coronary angiography and left
      ventriculography. Left ventricular pressure was determined throughout the cardiac
      cycle using a Millar 8Fr Minotip catheter; an echocardiogram, phonocardiogram,
      and ECG were simultaneously recorded to obtain left ventricular pressure-diameter
      loops. All the measurements were repeated before and after the intravenous
      administration of cicloprolol. Cicloprolol was administered at increasing doses
      of 0.05, 0.10, and 0.25 mg/kg until a cardiac output increase of at least 15%
      over basal values was achieved. A decrease of mean arterial pressure or cardiac
      output after cicloprolol was not observed in any patient. Cicloprolol
      administration significantly increased cardiac output (24%), stroke volume (22%),
      and peak positive dP/dt (25%); no significant changes in heart rate, systemic
      blood pressure, right atrial pressure, or pulmonary artery pressures were
      observed. No significant change in the echocardiographic parameters occurred.
      Among the indices of left ventricular diastolic function, the time constant of
      isovolumetric relaxation was significantly decreased (-43%) after cicloprolol;
      moreover, the left ventricular pressure-diameter loop in the protodiastolic phase
      was shifted to the left following cicloprolol infusion. This study confirms that
      in subjects with normal left ventricular function cicloprolol can improve resting
      left ventricular systolic function, and it shows that this action can also be
      attended by a more rapid isovolumetric relaxation, similar to what has been
      observed with other sympathomimetic amines.

PMID- 1360257
TI  - Dose-dependent effects of 6-hydroxy dopamine on deprivation myopia,
      electroretinograms, and dopaminergic amacrine cells in chickens.
AB  - We found that a single intravitreal injection of 6-hydroxy dopamine (6-OHDA) is
      highly efficient in blocking the development of deprivation-induced myopia in
      young chickens. To investigate the effects of 6-OHDA on retinal function, we
      studied electroretinograms (ERGs) in chickens aged 15-25 days, 4 days subsequent
      to the injection. Both spectral sensitivity and oscillatory potentials were
      tested. In addition, a histological examination was performed of dopaminergic
      amacrine cells labeled by a monoclonal antibody against tyrosine hydroxylase. We
      found that, at doses of 6-OHDA sufficient to suppress deprivation myopia
      entirely, no effect could be detected on either the ERGs or on the density and
      appearance of dopaminergic amacrine cells. For higher doses, spectral sensitivity
      and the number of dopaminergic amacrine cells declined gradually. In contrast, as
      doses increased, oscillatory potentials 1 and 2 grew in amplitude only to decline
      at the highest doses. The results indicate that (1) development of deprivation
      myopia requires normal retinal function and that (2) slight changes in the gains
      of dopaminergic pathways are sufficient to block the development of deprivation
      myopia.

PMID- 1360258
TI  - Triphasic sequence of neointimal formation in the cuffed carotid artery of the
      rabbit.
AB  - A nonocclusive silicone cuff placed around the rabbit carotid artery results in a
      diffuse intimal thickening. The early stages of this phenomenon were studied by
      light microscopy, immunohistochemistry, and electron microscopy. Neointimal
      formation appeared to be triphasic. The first phase started 2 hours after cuff
      placement, with vascular infiltration by polymorphonuclear leukocytes (PMNs). In
      the second phase, starting within 12 hours, 1.90 +/- 0.36% of the medial smooth
      muscle cells (SMCs) were replicating, as demonstrated by their immunoreactivity
      for proliferating cell nuclear antigen (PCNA). The third phase was characterized
      by the appearance, from day 3 onward, of subendothelial SMCs that were
      immunoreactive for alpha-SMC actin and vimentin. A few cells showed
      immunoreactivity for PCNA. During this phase all the PMNs disappeared, but SMC
      replication in the media was still present, as indicated by the presence of
      mitoses and the persisting immunoreactivity for PCNA (0.76 +/- 0.22% at day 7).
      In the third phase the number of subendothelial cells increased (104 +/- 15 SMC
      nuclei per section at day 7, of which 8.89 +/- 2.26% were PCNA-positive) and was
      associated with deposition of collagen type IV and fibronectin. At 14 days a
      complete, circular neointima was present and contained 2.13 +/- 0.28% replicating
      SMCs. The media showed 0.44 +/- 0.08% cell-cycling SMCs, which was still four
      times higher than normal. During the first week there was also a significantly
      higher PCNA activity in the media of sham-operated carotid arteries (no cuff
      present) than in nonsurgical ones. However, this did not lead to the formation of
      a neointima. We conclude that in the cuff system SMC replication in the media
      precedes the neointimal formation. The system can be used to study SMC
      replication, migration, and neointimal formation with minimal medial SMC damage.

PMID- 1360259
TI  - Nuclear Cardiology Today - 1992, II International Symposium. Cesena, Italy, May
      28-30, 1992.

PMID- 1360260
TI  - Predictors of the course of tardive dyskinesia in patients receiving
      neuroleptics.
AB  - As many patients still require maintenance neuroleptic medication, it is
      important to determine what factors affect the course of tardive dyskinesia (TD)
      during ongoing neuroleptic treatment. In this study the data are from a series of
      annual examinations using the Abnormal Involuntary Movement Scale (AIMS) in a
      cohort of outpatients. Average neuroleptic exposure at the commencement of the
      examinations was 10 yr. The data on AIMS scores at successive visits are analysed
      using autoregressive modeling. Two hundred thirty-five patients contributed the
      678 pairs of examinations. Separate analyses are reported for orofacial, limb
      truncal, and total AIMS scores. Different predictor variables emerged as
      important for orofacial and limb-truncal dyskinesia. Age, sex, being on
      anticholinergic medication, and two variables describing duration of neuroleptic
      exposure contributed to the outcome score for total AIMS score after 1 yr.

PMID- 1360261
TI  - Loss of the Kamin blocking effect in acute but not chronic schizophrenics.
AB  - Differences between research diagnostic criteria (RDC)-diagnosed acute and
      chronic schizophrenics and normal controls were studied using a Kamin blocking
      procedure. Blocking is an established animal learning procedure, thought by some
      researchers to reflect selective attention; decreased blocking indicates
      increased processing of irrelevant stimuli. It was predicted that this pattern
      would be obtained in acute schizophrenics, tested soon after admission, for two
      reasons: (1) evidence from previous clinical studies indicates that acute
      schizophrenics are more aware of nonsalient aspects of their environment than
      controls; and (2) blocking is disrupted in animals in a hyperdopaminergic state
      and restored by neuroleptic medication. This was the case: acute, but not
      chronic, schizophrenics showed disrupted blocking. This disruption was especially
      clear in those acute schizophrenics tested within 2 weeks of hospital admission.
      By the second test session (in a cross-over design), there was some evidence of
      normalization in performance in the acute schizophrenics. These findings are
      considered with regard to the dopamine hypothesis of schizophrenia.

PMID- 1360262
TI  - Drug distribution between blood and brain as a determinant of antipsychotic drug
      effects.
AB  - Concentrations of the neuroleptics haloperidol, bromperidol, fluphenazine,
      chlorpromazine and its metabolites nor-1- and nor-2-chlorpromazine, thioridazine
      and its metabolites mesoridazine, sulforidazine, and northioridazine, and
      promazine were estimated in serum and brain of rats by high performance liquid
      chromatography (HPLC) with electrochemical detection following 5 days of chronic
      administration of drug at typical doses (haloperidol, bromperidol, and
      fluphenazine 1 mg/kg/day; chlorpromazine, promazine, and thioridazine 25
      mg/kg/day). The observed ratio of brain-to-serum concentration of drug varied
      widely (0.18-62.5) among neuroleptics studied. High potency agents had more
      favorable brain-to-blood distribution than low potency agents, and a strong
      correlation (r = 0.734, p < 0.05) was observed between the brain-to-serum ratios
      of the neuroleptics and standard clinical doses of drug. This finding suggests
      that drug distribution is a significant determinant of clinical potency. For most
      neuroleptics, including drugs with high (fluphenazine, haloperidol) and low
      potency (thioridazine) such as dopamine D2 antagonists, concentration of drug in
      the brain was similar. If the results are applicable to patients, they suggest
      that the degree of dopamine D2 blockade achieved during treatment may vary by
      drug. Chlorpromazine and promazine were notable for producing high concentrations
      of drug in the brain at typical doses, suggesting that optimal doses might be
      lower than those in common use. These results may be important in designing and
      interpreting studies of the effects of neuroleptic drugs in animals and patients.

PMID- 1360264
TI  - Report on the Sixth International Symposium on Molecular Plant-Microbe
      Interactions, Seattle, July 11-16 1992.

PMID- 1360263
TI  - [Treatment of pain in tumor patients].

PMID- 1360265
TI  - Extramarital sex amongst the beets--Evidence for gene exchanges between sugar
      beet (Beta vulgaris L.) and wild beets: consequences for transgenic sugar beets.

PMID- 1360266
TI  - Subpopulations of normal peripheral blood and bone marrow cells express a
      functional multidrug resistant phenotype.
AB  - The multidrug-resistance gene, MDR1 is expressed in many normal tissues, but
      little is known about its expression in normal hematopoietic cells. Using the
      monoclonal antibody C219 and flow cytometric analysis, P-glycoprotein (P-gp) was
      found to be expressed in all peripheral blood (PB) subpopulations (CD4, CD8,
      CD14, CD19, CD56) except granulocytes. To specifically determine MDR1 gene
      expression, these PB subpopulations were isolated by fluorescence-activated cell
      sorting (FACS) and analyzed for MDR1 mRNA by polymerase chain reaction (PCR). All
      subsets were positive by PCR, but only minimal MDR1 mRNA was detected in
      monocytes and granulocytes. Significant efflux of Rhodamine-123 (Rh-123), a
      measure of P-gp function, was detected in CD4+, CD8+, CD14+, CD19+, and CD56+
      cells but not in granulocytes. Next, PCR-analysis was performed on FACS-sorted
      bone marrow (BM) cells to assess MDR1 expression in different maturational
      stages. Precursors (CD34+), early and late myeloid cells (CD33+/CD34+, CD33+/CD34
      ) as well as lymphocytes of the B-cell lineage (CD19+/CD10+, CD19+/CD10-)
      expressed the MDR1 gene. BM monocytic cells (CD33++/CD34-) were negative, and a
      very weak signal was detected in erythroid cells (glycophorin A+). Significant Rh
      123 efflux was found in CD34+, CD10+, CD33+, and CD33++ BM cells, but not in
      glycophorin A+ cells. We conclude that PB and BM lymphocytes, PB monocytes, BM
      progenitors, and immature myeloid cells, but not late BM monocytes, erythroid
      cells, and PB granulocytes, express MDR1 mRNA and a functional P-gp. These
      results have to be taken into account when MDR1 expression is determined in tumor
      samples containing normal blood cells.

PMID- 1360267
TI  - Expression and activity of the multidrug resistance P-glycoprotein in human
      peripheral blood lymphocytes.
AB  - P-glycoprotein (P-gp), the product of the MDR1 (multidrug resistance) gene, is a
      transmembrane efflux pump for different lipophilic compounds, including many
      anticancer drugs and fluorescent dyes. We have previously reported that the
      efflux of fluorescent dyes from lymphoid cells of human bone marrow was directly
      correlated with the cellular P-gp content. In the present study, we show that
      human peripheral blood lymphocytes (PBL) also express P-gp, and that P-gp
      expression correlates with the efflux of fluorescent dyes from PBL. This efflux
      was suppressed not only by chemical inhibitors of P-gp but also by a P-gp
      specific monoclonal antibody UIC2, thus providing direct evidence that it was
      mediated by P-gp. We have also characterized dye efflux and UIC2 reactivity in
      specific PBL subsets. P-gp was expressed in the majority of CD56+, CD8+, and
      CD20+ lymphocytes, but in less than one half of CD4+ cells. P-gp-mediated dye
      efflux was highly heterogeneous relative to the expression of CD56RA, CD56RO, Leu
      8, and HLA-DR antigens. No significant P-gp activity was detectable in CD14+
      monocytes. MDR1 expression in normal lymphocytes may be a determinant of
      multidrug resistance in the corresponding malignancies.

PMID- 1360268
TI  - Alterations of bone marrow sinus endothelium induced by ionizing irradiation:
      implications in the homing of intravenously transplanted marrow cells.
AB  - The endothelium of bone marrow sinuses is a continuous layer which is selective
      in its cellular transport. It is not known how selective and massive seeding of
      hemopoietic progenitor cells after intravenous transplantation of marrow cells
      occurs. We postulate that the conditioning irradiation could disrupt the
      endothelial barrier, thus permitting the "homing" of progenitor cells to occur.
      To demonstrate this phenomenon, we irradiated mice with doses ranging from 100
      2000 cGy-total body and studied perfusion-fixed marrow by transmission electron
      microscopy. The major finding was sloughing and denudation of plasma membrane,
      particularly on the luminal side of endothelium. Membrane vesiculation was also
      frequently seen in this border. Moreover, dilatation of the perinuclear space and
      rough endoplasmic reticulum was commonplace and testified to instability and
      fragility of the membrane system. Focal cytoplasmic swelling of endothelium was
      seen reflecting increased permissiveness of the endothelial barrier. Endocytosis
      and phagocytosis were increased in the marrow; and the endothelium, normally
      quiescent with regard to phagocytosis, was now overtly phagocytic. A dipogenecity
      of the adventitial layer was increased as hemopoietic function of marrow
      decreased. The end result of membrane alterations in the endothelium was the
      appearance of discontinuities in these cells, which form the essential element of
      bone marrow-blood barrier. Consequent to these discontinuities, the
      permissiveness of the endothelial barrier was enhanced and those cellular
      elements, such as mature, nonreticulated erythrocytes that are normally confined
      to the vascular space, now appeared in large number in the hemopoietic
      compartment. With low doses, these findings were transient and repair set in by 1
      2 weeks. With higher doses, total disruption of marrow-blood barrier occurred and
      the process did not seem to be repairable. We conclude that the conditioning
      irradiation before bone marrow transplantation is essential in disrupting the
      endothelial barrier and permitting large-scale entry of transplanted cells into
      the hemopoietic compartment.

PMID- 1360269
TI  - The structure and function of the blood-marrow barrier. Early ultrastructural
      changes in irradiated bone marrow sinus endothelial cells detected by vascular
      perfusion fixation.

PMID- 1360270
TI  - The human hematopoietic stem cell in vitro and in vivo.
AB  - A quantitative assay for a primitive human hematopoietic cell has been developed.
      The cell identified has been assigned the operational designation of long-term
      culture (LTC)-initiating cell based on its ability when cultured on supportive
      fibroblast monolayers to give rise to daughter cell(s) detectable by standard in
      vitro colony assays. Three lines of evidence support the view that the LTC
      initiating cell assay may allow the relatively specific enumeration of totipotent
      cells with in vivo reconstituting potential. These involve the demonstration: (1)
      that conditions in analogous murine long-term cultures stimulate the extensive
      amplification (self-renewal) of some totipotent long-term repopulating cells, (2)
      that most of the LTC-initiating cells in normal human bone marrow are
      phenotypically different from most of the colony-forming cells present in the
      same cell suspensions in their possession of a number of characteristics
      specifically associated with transplantable stem cells; and (3) that cultured
      marrow cells from patients with chronic myeloid leukemia which, after maintenance
      under LTC conditions for 10 days contain some normal LTC-initiating cells but no
      detectable leukemic LTC-initiating cells, can after autografting reconstitute the
      hematopoietic system with normal cells.

PMID- 1360271
TI  - Integrated hemopoiesis.

PMID- 1360272
TI  - Selective uptake of the somatostatin analog RC-160 across the blood-brain tumor
      barrier of mice with KHT sarcomas.
AB  - The development of somatostatin analogs with anti-tumor effects has raised hopes
      for their use in various cancers and tumors of the central nervous system.
      However, for many therapeutic agents, access to normal brain is retarded by the
      blood-brain barrier (BBB) and to tumor tissues by a blood-brain tumor barrier
      (BBTB). We examined the ability of RC-160, a somatostatin analog with known anti
      tumor activity, to cross the normal BBB and the BBTB in mice with brain sarcomas.
      In comparison with the normal BBB, the BBTB was about 10 times more permeable to
      the vascular marker albumin (radioactively labeled with 99mTc), but the BBTB
      still represents a substantial barrier. By contrast, the entry rate of RC-160,
      radioactively labeled with 125I, into brain sarcomas was 60 times higher than
      into normal brain tissue; more than 1% of the RC-160 injected i.v. was taken up
      by each gram of brain tumor. These results show that a brain tumor can
      selectively accumulate the potentially therapeutic agent RC-160.

PMID- 1360273
TI  - Comparative studies on the mode of action of proctolin and phorbol-12,13
      dibutyrate in their ability to contract the locust mandibular closer muscle.
AB  - The role of proctolin has been further investigated in the locust (Locusta
      migratoria) mandibular closer muscles. Radioactive calcium uptake measurements
      were made using protease-dissociated muscle cells. Both the phorbol ester,
      phorbol-12,13-dibutyrate, and proctolin produce tonic contractions which are
      associated with the influx of extracellular calcium. The thresholds for proctolin
      and the phorbol ester to contract the muscle were 1-10 nM and 10-100nM,
      respectively, while their respective thresholds for evoking measurable calcium
      influx into the muscle cells were 0.1-1 nM for proctolin, and 0.1-1 pM for
      phorbol-12,13-dibutyrate. The effect of phorbol-12,13-dibutyrate is blocked by a
      number of protein kinase inhibitors (at a concentration of 0.1 mM), suggesting
      that an activation of a protein kinase can lead to calcium influx. These
      inhibitors, however, do not block the effect of proctolin, indicating that these
      two compounds work through different pathways, possibly converging on the same
      final target. In light of this finding, a number of other compounds have been
      tested to try to ascertain how proctolin mediates an increased calcium influx.

PMID- 1360274
TI  - A unique RFLP haplotype at the phenylalanine hydroxylase locus in Czechoslovak
      Gypsies with phenylketonuria.

PMID- 1360275
TI  - Resistance mechanisms to topoisomerase poisons: the application of cell culture
      methods.
AB  - A survey is presented of two types of resistance to drugs acting on cellular
      topoisomerase enzymes, that occurring by altered drug transport and that
      occurring by altered target interaction. Particular attention is paid to the use
      of pairs of diagnostic drugs, one susceptible and one refractory to a particular
      resistance mechanism, in the determination of such resistance in cultured cells.
      Two pairs of drugs, each including the antitumor agent amsacrine, are used in the
      analysis of a number of cell lines. Also it is suggested that some normal
      hemopoietic precursor cells may exhibit two types of multidrug resistance, and
      that this should be taken into account in determining selectivity of
      topoisomerase-directed drugs for tumor cells.

PMID- 1360276
TI  - Activation of MDR1 (P-glycoprotein) gene expression in human cells by protein
      kinase C agonists.
AB  - P-glycoprotein, encoded by the MDR1 (multidrug resistance) gene, is a
      transmembrane efflux pump for various lipophilic compounds. MDR1 is expressed in
      several types of normal human tissues and in a variety of tumors, where its
      expression has been correlated with resistance to chemotherapy. Some P
      glycoprotein-overexpressing multidrug-resistant cell lines contain elevated
      amounts of protein kinase C (PKC). PKC activation was shown to increase the level
      of drug resistance in several cell lines, but the functional association of PKC
      with P-glycoprotein-mediated multidrug resistance remains unclear. We have
      studied the effects of lymphocyte-activating agents on P-glycoprotein activity in
      normal human lymphocytes, and found that 12-O-tetradecanoylphorbol-13-acetate
      (TPA), an efficient agonist of PKC, increased the activity as well as the levels
      of P-glycoprotein in these cells. TPA also increased P-glycoprotein expression in
      several cell lines derived from different types of leukemias and solid tumors.
      The increase in MDR1 gene expression was observed at both the protein and RNA
      levels. Induction of MDR1 mRNA was apparent as early as two hours after the
      addition of TPA. Diacylglycerol (DAG), a physiological stimulant of PKC, also
      increased the expression of MDR1 mRNA and P-glycoprotein. The induction of MDR1
      expression by TPA and DAG was suppressed by staurosporine, a protein kinase
      inhibitor. The results suggest that MDR1 gene expression in different cell types
      is regulated by a PKC-mediated pathway. This finding has implications for the
      emergence of multidrug resistance in vitro and in vivo.

PMID- 1360277
TI  - A randomized trial of reduced doses of azidothymidine in Japanese patients with
      human immunodeficiency virus type 1 infection.
AB  - Adverse reactions to the standard dose (1,200 mg/day-1,500 mg/day) of
      azidothymidine (AZT) are serious. An in vitro pharmacokinetic study of
      intracellular AZT-5'-triphosphate suggested the feasibility of a clinical trial
      with reduced doses of AZT. A randomized trial with reduced doses of AZT (group A;
      400 mg/day, n = 15, group B; 800 mg/day, n = 13), was conducted enrolling 28
      patients with human immunodeficiency virus infection. The effective rate of AZT
      on CD4+ lymphocyte counts was similar for both groups, but the duration of the
      effect of AZT was significantly longer in group A (p less than 0.05). In group B,
      adverse reactions were more frequently observed (p less than 0.01), and AZT was
      withdrawn or the dose was reduced more frequently (p less than 0.05). These
      results suggest that AZT at a dose of 400 mg/day is less toxic, and is more
      beneficial for long-term treatment.

PMID- 1360278
TI  - Genetic mapping of the murine gene and 14 related sequences encoding chromosomal
      protein HMG-14.
AB  - The high-mobility-group chromosomal protein HMG-14 preferentially binds to
      nucleosomal core particles of mammalian chromatin and may modulate the chromatin
      configuration of transcriptionally active genes. The human gene for HMG-14 has
      been localized to the Down syndrome region of Chromosome (Chr) 21 and may be
      involved in the etiology of this syndrome. Here we show, by means of genetic
      linkage analysis of interspecific and intersubspecific backcross mice, that the
      murine functional gene, Hmg14, is located on the distal end of mouse Chr 16, a
      region known to have conserved synteny with human Chr 21. In addition to the
      functional gene for HMG-14, both human and mouse genomes contain many related
      sequences that are probably processed pseudogenes. Here we map the locations of
      14 Hmg14-related sequences in two mouse genomes. The 14 mapped loci are widely
      dispersed on ten chromosomes (Chrs 3, 5, 7, 9, 11, 12, 16, 17, 19, and X) and can
      be detected efficiently with a single cDNA probe. Thus, the Hmg14 multigene
      family is well suited to serve as genetic markers for other linkage studies in
      mice.

PMID- 1360279
TI  - A detailed linkage map of subtelomeric murine chromosome 12 region including the
      situs inversus mutation locus IV.
AB  - A mouse model is an invaluable tool to tackle genesis of human congenital
      diseases that have so far eluded human studies. Homozygote for the i.v. mutation,
      the murine Si/Col strain presents a left-right lateralization defect of thoracic
      and abdominal organs and heart defects very similar to human ones. This i.v.
      mutation has been mapped to the region between the Aat and Igh-C loci, suggesting
      the presence of an equivalent human gene in the human syntenic 14q3 region. A
      precise linkage map of the region is, therefore, of great interest since it will
      contribute to the genetic approach of the i.v. gene. Analysis of 242 back-cross
      progeny from Mus musculus (MAI) or spretus strains of mice and SI/Col mice has
      allowed mapping of the i.v. gene to a linkage group of eight markers. It includes
      four genes: Aat (alpha 1-antitrypsin), Ckb (creatine kinase, brain form), Crip
      (cysteine-rich intestinal protein), and Igh-C (immunoglobulin heavy chain
      constant region complex); three murine microsatellites: D12Mit6, D12Mit7, and
      D12Mit8; and one new marker, D12Mtp1, defined by a minisatellite human probe,
      pYNZ2. After analysis of the data by the LINKAGE program, the following
      multilocus map has been constructed: centromere-D12Mit6-6.9 cM-D12Mit7-1.7 cM
      D12Mtp1-2.6 cM-Aat-5.0 cM-(Ckb, Igh-C)-0.4 cM-D12Mit8-0.4 cM-Crip-11.2 cM-i.v.
      telomere. This map differs from the previous map in placing i.v. locus telomeric
      to Igh-C. D12Mit6 and D12Mit7 are now precisely mapped centromeric to the locus
      Aat. In addition, a new locus D12Mtp1 is located between Aat and D12Mit7.

PMID- 1360280
TI  - Isolation and mapping of four new DNA markers from mouse chromosome 4.

PMID- 1360281
TI  - Free radicals and neurotransmitters in gerbil brain. Influence of age and
      ischemia reperfusion insult.
AB  - In gerbil brain, levels of hydroxyl radicals (OH.) and neurotransmitters such as
      glutamate, aspartate, GABA (gamma aminobutyric acid) are low at birth, reach a
      plateau and decrease with age. On the other hand, when gerbils are exposed to an
      ischemia reperfusion insult (IRI) the older animals have a higher stroke index
      and hydroxyl radical as well as glutamate and other neuromediators are
      concomitantly increased. This discrepancy is probably due to differences in the
      ability of old individuals to respond to oxidative stress. The still incompletely
      understood relationship between oxidative damage to proteins and accumulation of
      amino acids, which have an important role as neurotransmitters at physiologic
      concentrations, but may become neurotoxic at high concentrations, is discussed.

PMID- 1360282
TI  - Free radicals, lipid peroxidation, SOD activity, neurotransmitters and choline
      acetyltransferase activity in the aged rat brain.
AB  - The mechanism of aging is suggested to be related to oxygen free radicals. Free
      radicals, lipid peroxidation and SOD activity have been reported to be increased
      in the aged brain. A Japanese herbal medicine, Sho-saiko-to-go-keishi-ka
      shakuyaku-to (TJ-960), which has scavenging activities against hydroxyl radicals,
      superoxide, 1,1-diphenyl-2-picrylhydrazyl radicals, carbon-centered radicals and
      alpha-tocopheroxyl radicals, decreased carbon-centered radicals and
      thiobarbituric acid reactive substances (TBARS) levels in the aged rat brain
      after a 3-week oral administration of 5% TJ-960 solution. TJ-960 elevated
      superoxide dismutase (SOD) activity in the cytosol fraction of the hippocampus
      and hypothalamus of aged rats. It decreased norepinephrine and 5
      hydroxytryptamine (5-HT) levels in the hypothalamus and increased the 5-HT level
      in the cerebellum. TJ-960 treatment increased choline acetyltransferase activity
      in aged rats. As herbal medicines do not generally have harmful side effects,
      antioxidant TJ-960 appears to be a suitable prophylactic agent against some
      neuronal symptoms of aging.

PMID- 1360284
TI  - The safety of beta agonists in asthma.

PMID- 1360283
TI  - Protein modification in aging.
AB  - During aging a number of enzymes accumulate as catalytically inactive or less
      active forms. The age-related changes in catalytic activity are due in part to
      reactions of the protein with "active" oxygen species such as ozone, singlet
      oxygen, or with oxygen free radicals as are produced during exposure to ionizing
      radiation or to metal ion catalyzed oxidation (MCO) systems. The levels of
      oxidized proteins in cultured human fibroblasts from individuals of various ages
      and in liver and brain extracts of rats of different ages increase progressively
      with age, and in old rats can represent 30-50% of the total cellular protein. The
      age-related increase in oxidized protein in rat liver and brain tissue is
      accompanied by a loss of glutamine synthetase (GS) and glucose-6-P dehydrogenase
      (G-6-PDH) activities, and to a decrease in the level of cytosolic neutral
      protease activity which is responsible for the degradation of oxidized
      (denatured) protein. Of particular significance are the results of experiments
      showing that similar age-related changes occur in the gerbil brain and that these
      changes are accompanied by a loss of short-term memory as measured by the radial
      arm maze technique. Chronic treatment (intraperitoneal injections) of old animals
      with the free radical spin-trap reagent, N-tert-butyl-alpha-phenylnitrone (PBN)
      resulted in normalization of the several biochemical parameters to those
      characteristic of the young animals; coincidentally, the short-term memory index
      was restored to the young animal values. These results provide the first evidence
      that there is likely a linkage between the age-dependent accumulation of oxidized
      enzymes and the loss of physiological function.

PMID- 1360286
TI  - Glutathione homeostasis in rats chronically treated with ethanol. Evidence for an
      increased hepatic GSH export in vivo.
AB  - The influence of chronic ethanol feeding to rats on the hepatic glutathione (GSH
      and GSSG) system (synthesis, catabolism, export) and on the GSH and GSSG
      concentrations in extrahepatic tissues was investigated. Histological examination
      of livers from ethanol pretreated rats revealed a minor dilatation of the hepatic
      sinusoids. After ethanol administration the distribution pattern of gamma
      glutamyltranspeptidase (enzymehistochemistry) was nearly unchanged, but the
      hepatic activity of this enzyme was increased. The ethanol pretreatment led to a
      decrease in hepatic GSH content. The hepatic activity of the GSSG-reductase were
      increased after ethanol treatment whereas the activities of the GSH synthesizing
      enzymes (gamma-glutamyl-cysteinyl-synthetase and GSH-synthetase) were not
      affected. A strong increase in sinusoidal GSH export was found in the ethanol
      pretreated rats. The GSH- and GSSG concentrations of brain, lung, kidney and
      skeletal muscle were unchanged. It can be concluded that the ethanol-induced
      alteration of the hepatic GSH metabolism is caused mainly by changes of the
      sinusoidal membrane of the hepatocytes (direct effect of ethanol on the
      sinusoidal GSH carrier) leading to an increased GSH export into plasma. This
      effect should not due to an increased extrahepatic requirement for GSH.

PMID- 1360285
TI  - First International Workshop on Familial Defective apo B-100, Munich, November
      1991.

PMID- 1360289
TI  - Potyvirus taxonomy. Workshop. Braunschweig, Federal Republic of Germany, 2-4
      September 1990.

PMID- 1360288
TI  - Hepatitis C virus infection in patients with idiopathic hemochromatosis (IH) and
      porphyria cutanea tarda (PCT).
AB  - The prevalence of HCV antibodies in IH and PCT patients was examined. It was
      found that both groups are characterized by increased incidence of HCV infection.
      These results suggest a possible connection between HCV and iron overload.

PMID- 1360290
TI  - Effects of excess protein intake on nitrogen utilization in young men.
AB  - The efficiency of nitrogen (N) utilization was studied in 12 young male subjects.
      Protein intake levels were adjusted from moderate (1.08 and 1.18 g
      protein/kg/day) to high (1.74 and 2.00 g protein/kg/day). All of the food was
      supplied in the form of a normal mixed Chinese diet. Six subjects were admitted
      to a metabolic unit at a time for 56 days, in two consecutive periods. The
      results indicate that a higher protein intake causes more N excretion in urine
      and feces. Biologic value (BV) and net protein utilization (NPU) were markedly
      decreased during the high protein intake (HPI) period. However, a significant
      increase in the N balance was found in the presence of excessive protein intake.
      Digestibility of protein seemed to increase during the HPI period, with the
      apparent digestibility of the dietary protein being about 83% to 90%. We conclude
      from this study that excessive N intake reduces the efficiency of N utilization,
      but still results in a positive N balance in adult human subjects.

PMID- 1360287
TI  - The role of the promoter in the expression of the PCNA gene.
AB  - G1-specific temperature-sensitive (ts) mutants of the cell cycle arrest in G1
      after serum stimulation at the restrictive temperature. Under these conditions,
      the RNA levels of late growth-regulated genes (such as DNA polymerase alpha,
      PCNA, thymidine kinase, and core histones) are markedly decreased or even
      undetectable, while early growth-regulated genes (for instance, c-myc) are
      normally expressed, and certain promoters are actually super-induced. We have
      used the human PCNA gene transfected into TK-ts13 cells (a G1-specific ts mutant)
      to investigate whether the inhibition of gene expression caused by this type of
      growth inhibition occurs at a transcriptional or post-transcriptional level.
      Constructs were made in which the 5' and 3' flanking sequences of the human PCNA
      gene were replaced by the corresponding elements of the SV40 T antigen coding
      gene. Using these constructs and data from run-on assays and RT-PCR, we conclude
      that the failure of expression of the PCNA gene in G1-arrested TK-ts13 cells
      occurs at the transcriptional level.

PMID- 1360291
TI  - Relationship between brain serotonin and calmodulin in young, genetically obese
      (ob/ob) mice.
AB  - The possible relationships between altered brain serotonin and calmodulin
      contents on the development of obesity were studied. Eight groups of mice
      separated by differences in phenotype, sex and age were used in this study. The
      brain contents of tryptophan, serotonin, 5-hydroxyindoleacetic acid (5-HIAA) and
      calmodulin were assayed. The contents of brain tryptophan showed no significant
      differences in any of the mice. The amount of brain serotonin in obese mice was
      82% higher than that in their lean counterparts at four weeks of age, but only
      11% higher at eight weeks of age. Regardless of age and sex, brain serotonin was
      positively correlated to the brain calmodulin in the lean mice (r = 0.559, p <
      0.01), yet this was not found in obese mice. There was a strong positive
      correlation between serotonin and 5-HIAA in all mice (r = 0.679, p < 0.001). The
      elevated amount of serotonin in the brain of four-week-old obese mice is
      suggested to have important effects on thermoregulation in young genetically
      obese mice. The results also suggest that abnormal brain serotonin synthesis in
      obese mouse regulated by calmodulin might interact with certain factors, such as
      calcium ions, to complete the activation of serotonin-synthesized enzymes in the
      development of obesity.

PMID- 1360292
TI  - Inheritance of hypertrophic cardiomyopathy in Chinese--M-mode and two-dimensional
      echocardiographic analysis of 28 families.
AB  - To determine the mode of inheritance and degree of penetrance of hypertrophic
      cardiomyopathy (HC) in Chinese, 132 family members of 28 probands with HC were
      assessed by M-mode and two-dimensional echocardiography. Of these 132, 103 cases
      were first-degree relatives of the probands. Twenty-seven (20.4%) family members,
      including 19 cases of first-degree relatives of the probands, had HC. Familial
      occurrence of HC was noted in 13 (46.4%) families. In 10 families, the affected
      relatives were identified in successive generations, and the mode of inheritance
      was most consistent with an autosomal dominant trait. The frequency with which HC
      was identified in relatives increased significantly with the number of subjects
      studied and a positive family history of sudden death. Subgroup analysis, using
      multivariate logistic regression analysis, revealed that increasing age was
      independently associated with a higher frequency of definite cases in first
      degree relatives of the probands. In contrast, by multivariate analysis, there
      were no significant differences between frequency of definite cases in female and
      male relatives or in different familial relationships (parent, sibling,
      offspring) to the probands.

PMID- 1360293
TI  - Comparison of sodium transport processes of human and rat erythrocytes in
      hypertension.
AB  - Erythrocytes of normotensive and hypertensive humans, as well as Sprague-Dawley,
      Wistar-Kyoto and spontaneously hypertensive rats, were prepared to have similar
      ionic compositions adequate for determining the activities of lithium-sodium (Li
      Na) countertransport and sodium (Na) pump. The rate of Li-Na countertransport was
      significantly higher in erythrocytes of hypertensive subjects. This activity was
      not detected in rat erythrocytes, at two different ages, and over a six-fold of
      lithium (Li) content. Activities of Na pump were not significantly different
      among various groups. Human cells, in general, had a higher activity than rat
      cells; among rat cells, spontaneously hypertensive rats had a higher rate of
      sodium pump. Both Na-independent Li efflux and ouabain-insensitive Na efflux were
      significantly higher in rat erythrocytes than in human cells. Thus, employing the
      same methods, we have determined that while the properties of Na pump were
      similar in human and rat erythrocytes, Li-Na countertransport did not operate in
      the erythrocytes of either normotensive or hypertensive rats.

PMID- 1360294
TI  - Antithrombin III activity in normal and toxemic pregnancies.
AB  - From August 1989 to October 1990, 83 pregnant Chinese women were the subjects for
      measuring the levels of plasma functional antithrombin III (AT III) activity. The
      correlations of AT III activity with perinatal outcome and the changes in
      maternal hepatorenal function were analyzed. The population was divided into four
      groups: Group I (n = 30), normal pregnancies; Group II (n = 23), mild pre
      eclampsia; Group III (n = 26), severe pre-eclampsia; and Group IV (n = 4),
      eclampsia. The results demonstrated that: 1) AT III activity decreased with the
      severity of toxemia (p < 0.001), 2) AT III activity correlated with the degree of
      perinatal outcome and maternal morbidity, and 3) reduction of AT III activity
      correlated with impairment of maternal hepatorenal function. In conclusion,
      plasma AT III activity is a valuable parameter in the evaluation of toxemia.

PMID- 1360295
TI  - Rat liver regeneration after partial hepatectomy: effects of insulin, glucagon
      and epidermal growth factor.
AB  - This study evaluated the role of insulin, glucagon and the epidermal growth
      factor (EGF) on liver regeneration after partial hepatectomy. Male Wistar rats,
      weighing approximately 200 g, were used. A partial hepatectomy, with resection of
      the medial and left lateral lobes (67.31%), was performed on the control group
      and seven hormone-treated groups: insulin, glucagon, EGF, insulin plus glucagon,
      insulin plus EGF, glucagon plus EGF, and a combination of the three hormones. The
      hormones were administered subcutaneously two days prior to the partial
      hepatectomy. The groups administered insulin were allowed to drink 20% glucose in
      water. Another group of rats received simulated operations, i.e., only a
      laparotomy was performed. The rats were killed at six, 24, 48 and 72 hours after
      the operation. Remnant liver weight, deoxyribonucleic acid (DNA) content, rate of
      DNA synthesis, mitotic index, blood glucose and serum insulin levels were
      measured. The results showed that: 1) the effects of single hormone
      administration on posthepatectomy liver regeneration were not obvious; 2)
      combined administration of insulin and glucagon increased the weight of the
      remnant liver, the DNA content, and the rate of DNA synthesis; 3) the combined
      administration of insulin, glucagon, and EGF increased the regeneration based on
      the remnant liver weight and mitotic index; and 4) there was no concordance
      between the change in blood glucose levels and the effect of hormones during
      liver regeneration.

PMID- 1360296
TI  - Hepatitis B virus infection among aboriginal children in eastern Taiwan.
AB  - Hepatitis B virus (HBV) infection is endemic in Taiwan, with 15-20% of the adult
      population carrying the surface antigen (HBsAg). Hualien in Eastern Taiwan is
      relatively isolated from other parts of the island by the Central Mountains. The
      status of HBV infection among mountain aborigines in Hualien has not been studied
      on a large scale before. A survey of serum HBsAg and its antibody (anti-HBs) was
      conducted in 1989. A total of 3,287 children from 27 primary schools in three
      mountainous counties of Hualien were tested. The carrier rate (HBsAg positive)
      for the whole group was 31.9%, and the infection rate (HBsAg and/or anti-HBs
      positive) was 80.7%. Both the carrier rate and infection rate of 1,618 boys were
      significantly higher than those of 1,669 girls (35.7% vs 28.3% and 83.0% vs
      79.3%, respectively, p < 0.001). The carrier rates of children in the first to
      sixth grades were 29.4%, 35.0%, 31.5%, 30.8%, 33.3% and 32.0%, and the infection
      rates were 74.9%, 79.0%, 80.1%, 82.6%, 83.3% and 84.1%, respectively. The
      infection rate increased significantly with age (p < 0.05). The results show that
      HBV infection is a serious problem among the children of mountain aborigines in
      Hualien, with nearly one-third of them carrying HBsAg. Aggressive vaccination, as
      well as public health education programs, are greatly needed.

PMID- 1360297
TI  - Urodynamic findings in interstitial cystitis.
AB  - Fifty patients with irritative voiding symptoms and a painful bladder when full
      were engaged in this study to clarify the role of urodynamics in the diagnosis of
      interstitial cystitis (IC). Patients underwent urodynamic study, cystoscopic
      hydrodilatation of the bladder under general anesthesia and bladder biopsy.
      Twenty-eight women and two men who presented with signs of glomerulations or
      petechial hemorrhage of the bladder mucosa were classified as having IC, while 20
      women without this characteristic were classified as having non-IC. A
      hypersensitive urge sensation, a small bladder capacity, a lower maximal flow
      rate and an abnormal flow pattern were observed in both groups of patients, but
      no significant difference was noted. More IC patients had a lower bladder
      compliance than non-IC patients (p < 0.025), and the maximal bladder capacity
      under anesthesia was smaller in IC patients (p < 0.05). However, there does not
      seem to be any definite correlation to the pathologic findings, except in
      patients with marked bladder inflammation, in whom a small capacity and severe
      clinical symptomatology were found.

PMID- 1360298
TI  - Methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) for advanced TCC of
      urothelium.
AB  - After the introduction of methotrexate, vinblastine, adriamycin and cisplatin
      combination (M-VAC) chemotherapy for transitional cell carcinoma (TCC) of the
      urothelium, the reported response and survival rates improved when compared with
      the previous regimens. From July 1989 to March 1991, 43 consecutive cases of
      invasive or metastatic TCC that had received at least one course of M-VAC
      treatment were collected by a computer-assisted search and analyzed. The overall
      response rate, including complete response (CR) and partial response (PR), was
      44% (CR, 16%; PR, 28%). Tumors originating from the renal pelvis or bladder
      responded better than those from the ureter (kidney, 57%; bladder, 42%; and
      ureter 30%). Lymph node, soft tissue, lung metastases and local recurrent tumors
      had a greater chance of response than bone or liver metastases. Although patients
      from the blackfoot disease endemic area seemed to respond better than those from
      the nonendemic area, there was no statistically significant survival benefit. The
      duration of follow-up ranged from nine to 38 months. The length of survival of
      nonresponders ranged from one month to 19 months (median, eight months; mean,
      seven months). Ten of the 19 responders relapsed, and the others were still
      responding. Three patients (7%) survived two years, disease-free. Although the
      response rate improved, the chance of long-term survival was still unsatisfactory
      in our study.

PMID- 1360299
TI  - Cognitive development of children prenatally exposed to polychlorinated biphenyls
      (Yu-Cheng children) and their siblings.
AB  - An intoxication episode resulting from rice-bran oil (Yu-Cheng) contaminated with
      polychlorinated biphenyls (PCBs) occurred in Taiwan from 1978 to 1979. After that
      episode, the authors found 15 Yu-Cheng children who were born to intoxicated
      mothers after their documented consumption of PCB-contaminated oil; these
      children had older siblings, born before PCB exposure, without prenatal PCB
      exposure. The cognitive development of these Yu-Cheng children and the youngest
      of their elder siblings were assessed annually from 1985 to 1990 using the
      Chinese version of the Wechsler Intelligence Scale for Children, Revised Version
      (WISC-R) for those over six years of age. Compared with their elder siblings, the
      Yu-Cheng children scored significantly lower (p < 0.05) on the verbal
      intelligence quotient, by 6.8-16.1 points; on performance IQ by 10.2-18.4 points;
      and on full-scale IQ by 8.9-18.5 points, during the six measurements performed
      from 1985 to 1990. The differences in WISC-R IQ scores between the two groups
      have remained unchanged during these six years of follow-up.

PMID- 1360300
TI  - Pregnancy after transfer of frozen-thawed human embryos.
AB  - Cryopreservation of human embryos has been successfully applied in in vitro
      fertilization (IVF) and embryo transfer (ET) programs at the National Taiwan
      University Hospital since 1988. Our preliminary results with 120 frozen-thawed
      embryos in 31 transfer cycles showed that the survival rate of frozen embryos was
      66%. Following transfer, the implantation rate and clinical pregnancy rate were
      6.5% and 13%, respectively. Four clinical pregnancies and one preclinical
      pregnancy following a frozen-thawed embryo transfer were achieved. Two normal
      male babies have been delivered and another pregnancy is progressing without any
      problem.* Unfortunately, one pregnancy was terminated due to intrauterine fetal
      death discovered at the 10th week of gestation; chromosome abnormality (47, XX,
      +5) of the fetus was found. The single preclinical pregnancy showed an elevation
      of serum beta-human chorionic gonadotropin levels for three consecutive weeks
      following ET, but no definite gestational sac was visualized by transvaginal
      ultrasound.

PMID- 1360301
TI  - Laparoscopic hysterectomy: preliminary report of 24 cases.
AB  - From March to November 1991, 24 patients underwent laparoscopic hysterectomies at
      Chang Gung Memorial Hospital, Taipei. The indications for hysterectomies included
      seven patients with adenomyosis, 14 with myoma uteri, one with intractable
      menorrhagia, and two with endometriosis and severe pelvic adhesions. The
      surgeries were performed using the techniques of videolaparoscopy, including a
      combination of Kleppinger bipolar forceps for hemostasis and scissors and/or CO2
      laser for lysis of adhesions. The mean blood loss was 210 mL; there was one
      bladder injury during these procedures. Most of the patients were discharged on
      the second postoperative day. The advantages of a laparoscopic hysterectomy
      include a short hospitalization, low blood loss and less postoperative
      discomfort. Laparoscopic hysterectomy is a cost-effective and safe procedure.

PMID- 1360302
TI  - Premenstrual tension syndrome with periodic bulimia nervosa: report of a case and
      review of the literature.
AB  - Premenstrual tension syndrome (PMS) is well known in its epidemiology, etiology,
      symptomatology and treatment. However, PMS characterized by bulimic episodes is
      rare. We report a case of a 20-year-old university student who suffered from
      uncontrollable binge eating premenstrually for six months before visiting our
      clinic. She was obese without any other notable family or medical history except
      the PMS noted for two years. A daily food diary for two consecutive menstrual
      cycles showed that the mean differences in caloric intake between premenstrual
      and postmenstrual days of two menstrual cycles were 679 and 703 calories,
      respectively. The greater peaks in caloric level were noted within the third to
      fifth days prior to the onset of menstruation. All binge episodes occurred in the
      premenstrual period, especially within five days prior to menstruation. In this
      report, we will also review the literature on the relationship between PMS and
      dietary intake, as well as bulimia nervosa.

PMID- 1360303
TI  - Neurenteric cyst at craniocervical junction: report of a case.
AB  - The authors report a rare case of neurenteric cyst at the foramen magnum
      presenting with a central cord syndrome and dysfunction of the lower cranial
      nerves. A magnetic resonance imaging study showed a cystic lesion over the lower
      medulla oblongata and C1-2 spinal cord. Differentiation between a neurenteric
      cyst and an epidermoid cyst was difficult. Successful total removal of the cyst
      was performed. The lesion consisted of an enteric cyst lined with a mucus
      secreting columnar epithelium, containing highly proteinaceous supernatant and
      thick mucus deposit. The patient recovered dramatically after surgery.

PMID- 1360304
TI  - Urinary kallikrein excretion in non-insulin-dependent diabetes mellitus.
AB  - To investigate the status of urinary kallikrein excretion (UKE) in patients with
      non-insulin-dependent diabetes mellitus (NIDDM), we measured UKE in 31 NIDDM
      patients. They ranged in age from 40 to 70 years (mean, 54.3 +/- 7.8 years),
      comprising 18 males and 13 females. Their creatinine clearance (Ccr) was 91.6 +/-
      5.5 mL/min, and the daily excretion rate of protein was 1.15 +/- 0.72 g/24 hours.
      Twenty-five normal persons, aged from 37 to 63 years (mean, 51.7 +/- 8.2 years),
      comprising 14 males and 11 females, were enrolled as controls. The NIDDM patients
      were further divided into two groups. Group A (n = 21) had regular blood sugar
      control, while Group B (n = 9) had poor blood sugar control. The autonomic
      nervous function was tested in 15 patients to study its relationship with UKE.
      UKE was measured by spectrophotometric assay of the kallikrein enzymatic product
      on the synthetic substrate S-2266. Autonomic function was evaluated by
      cardiovascular reflex tests. The results showed that UKE was elevated in Group B,
      but depressed in Group A (normal vs A vs B: 9.6 +/- 1.0 vs 4.8 +/- 0.9 vs 14.4 +/
      2.7 nkat/24 hours). The UKE/Ccr ratio was similarly elevated in Group B and
      reduced in Group A (normal vs A vs B: 0.1 +/- 0.01 vs 0.05 +/- 0.01 vs 0.18 +/-
      0.04 nkat. mL/day.minute). There was no significant correlation between UKE or
      the UKE/Ccr ratio and the Valsalva ratio, the 30:15 ratio, or postural blood
      pressure change. These results suggest that NIDDM patients have abnormal urinary
      kallikrein excretion levels that are influenced by blood sugar control. The
      abnormal UKE/Ccr ratio suggests that intrarenal abnormality in the renal
      kallikrein-kinin system exists in NIDDM patients.

PMID- 1360306
TI  - Superior mesenteric artery syndrome as a complication in hip spica application
      for immobilization: report of a case.
AB  - A 10-year-old girl who had a pelvic and femoral osteotomy for congenital
      dislocation of her right hip was immobilized with a hip spica. On the 28th
      postoperative day, she had upper abdominal pain, distention and bilious vomiting.
      An upper GI series demonstrated complete obstruction of the duodenum at the third
      portion of the duodenum in a supine position; however, the barium passed the
      obstruction site slowly when the patient assumed a lateral or prone position. She
      was successfully treated conservatively with nasogastric decompression, fluid
      replacement, proper positioning and hyperalimentation. Superior mesenteric artery
      syndrome is a rare complication in patients immobilized in a body cast or hip
      spica. Early diagnosis and proper treatment usually leads to an uneventful
      convalescence.

PMID- 1360305
TI  - Correlation between ELISA and recombinant immunoblot assay in serum samples
      positive for anti-HCV.
AB  - To determine the false-positivity of antibody to hepatitis C virus (HCV) (anti
      C100-3), the correlation between ELISA optical density (OD), anti-HCV titer and
      recombinant immunoblot assay (RIBA) in 87 anti-HCV-positive sera was analyzed.
      The results showed that > 90% of the serum samples with an anti-HCV OD > 2.0 or
      with titers > 10 x were RIBA reactive. These findings are applicable in daily
      clinical practice.

PMID- 1360307
TI  - Non-association between 9.2 KB PvuII RFLP and seronegative spondyloarthropathies
      in Spain.
AB  - Several studies of DNA restriction fragment length polymorphism (RFLP) in
      ankylosing spondylitis (AS) have been carried out. The association between a
      recently identified class I HLA 9.2 kb PvuII RFLP and AS remain controversial. In
      order to evaluate this possible association in an Euro-Caucasian population, the
      genomic DNA of 42 AS patients and 18 patients with Reiter's syndrome (RS) and 42
      healthy controls was analysed. Non-association between 9.2 kb PvuII RFLP and AS
      or RS was observed. As described previously, a strong association between this
      fragment and HLA-A3 and/or HLA-A9 antigens was demonstrated. A study of two
      families showed that this RFLP segregates with HLA-A3 and/or HLA-A9 and
      independently of the HLA-B27. Our findings support the view that the 9.2 kb PvuII
      fragment is not universally associated with AS.

PMID- 1360308
TI  - Late malignancy risk in urology.
AB  - The long-term survival of children with congenital urological abnormalities is
      now taken for granted. In general, they have been found to grow up well after
      many operations and often in the face of considerable handicaps. Their survival
      carries with it numerous complications, the most frightening of which is the
      development of cancer. Successful treatment of congenital abnormalities does not
      excuse the patient from developing cancers to which the general population is
      prone, but some conditions and some treatments raise specific risks.

PMID- 1360309
TI  - Physical and mental fatigue: metabolic mechanisms and importance of plasma amino
      acids.
AB  - There are at least 5 metabolic causes of fatigue, a decrease in the
      phosphocreatine level in muscle, proton accumulation in muscle, depletion of the
      glycogen store in muscle, hypoglycaemia and an increase in the plasma
      concentration ratio of free tryptophan/branched-chain amino acids. Proton
      accumulation may be a common cause of fatigue in most forms of exercise and may
      be an important factor in fatigue in those persons who are chronically physically
      inactive and also in the elderly: thus, the aerobic capacity markedly decreases
      under these conditions, so that ATP must be synthesized by the much less
      efficient anaerobic system. A marked increase in the plasma fatty acid level,
      which may occur when liver glycogen store is depleted and when hypoglycaemia
      results, or during intermittent exercise when the rate of fatty acid oxidation
      may not match the mobilisation of fatty acids, could be involved indirectly in
      fatigue. This is because such an increase in the plasma level of fatty acids
      raises the free plasma concentration of tryptophan, which can increase the entry
      of tryptophan into the brain, which will increase the brain level of 5
      hydroxytryptamine: there is evidence that the latter may be involved in central
      fatigue. In this case, provision of branched-chain amino acids in order to
      maintain the resting plasma concentration ratio of free tryptophan/branched-chain
      amino acids should delay fatigue--there is prima facie evidence in support of
      this hypothesis. This hypothesis may have considerable clinical importance.

PMID- 1360310
TI  - Transplantation of embryonic mesencephalic and medullary raphe neurons to the
      neostriatum of rats with unilateral 6-hydroxydopamine lesions.
AB  - The implantation of dopamine-rich mesencephalic grafts into the 6-hydroxydopamine
      (6-OHDA)-lesioned neostriatum of rats was accompanied by marked hyperinnervation
      by serotonin (5-HT) fibers. The purpose of this study was to examine the
      possibility that the graft-derived 5-HT hyperinnervation is governed by target
      related effects present in the host neostriatum and the question of whether
      grafts rich in 5-HT cells can ameliorate the drug-induced motor asymmetry
      resulting from unilateral 6-OHDA lesions. Rats were allocated to one of two
      groups: lesion plus mesencephalic raphe grafts (group R5-HT/L); and lesion plus
      medullary raphe grafts (group C5-HT/L). A third group, sham-lesion plus
      mesencephalic raphe grafts (group R5-HT/S) was included. Complete recovery of (+)
      amphetamine-induced rotation was observed only in rats which received 5-HT grafts
      derived from medullary raphe neurons. There was no marked recovery of apomorphine
      induced rotation in either of the R5-HT/L and C5-HT/L groups.
      Immunohistochemistry showed that the R5-HT/L and C5-HT/L groups had 5-HT
      hyperinnervation in the neostriatum of the lesioned side. There was no target
      related effect of the 6-OHDA-lesioned neostriatum specific for the different
      types of 5-HT tissue. It seems likely that the 5-HT tissue derived from the
      medullary raphe may contain additional neurotransmitters which contribute to the
      behavioral recovery.

PMID- 1360311
TI  - Stereoselective effects of central alpha 2-adrenergic agonist medetomidine on in
      vivo catechol activity in the rat rostral ventrolateral medulla (RVLM).
AB  - The stereoselective central effects of a novel, highly potent and selective alpha
      2-agonist medetomidine on adrenergic neuronal activity, reflected by changes in
      catechol oxidation current, in the rostral ventrolateral medulla of the halothane
      anesthetized rat were examined using in vivo differential normal pulse
      voltammetry. Dexmedetomidine, the active isomer, significantly decreased catechol
      oxidation current to 33.4 +/- 4.5% of baseline when given centrally (1 microgram,
      i.c.v.) and to 10.3 +/- 3.9% of baseline when given systemically (50
      micrograms/kg, i.v.). Dexmedetomidine also significantly reduced mean arterial
      blood pressure by 19.9% following central administration but significantly
      increased mean arterial blood pressure by 59.9% following systemic
      administration. Levomedetomidine, the inactive isomer, had no effect on catechol
      oxidation current or blood pressure. The depressant effects of dexmedetomidine on
      catechol oxidation current were reversed by the selective alpha 2-adrenoceptor
      antagonist atipamezole (2 micrograms, i.c.v. or 200 micrograms/kg, i.v.). The
      results of the present study demonstrate, to our knowledge, for the first time
      the central stereoselective effects of medetomidine and antagonism by atipamezole
      on rostral ventrolateral medulla activity in the anesthetized rat.

PMID- 1360312
TI  - CNQX increases spontaneous inhibitory input to CA3 pyramidal neurones in neonatal
      rat hippocampal slices.
AB  - Whole-cell recordings were made from immature CA3 pyramidal neurones in the rat
      hippocampal slice. The addition of the glutamate receptor antagonist, CNQX,
      caused a robust increase in the frequency of spontaneous inhibitory post-synaptic
      currents (IPSC) concomitant with the expected reduction of excitatory drive to
      these neurones. This effect of CNQX was not shared by structurally related
      quinoxalinediones or kynurenic acid, which are also antagonists of non-NMDA
      glutamate receptors. This effect of CNQX was abolished by tetrodotoxin suggesting
      that an increase in interneurone spiking was responsible for the IPSCs.
      Recordings from stratum radiatum interneurones of CA3 confirmed this suggestion,
      since some interneurones were directly depolarized by CNQX. The excitation by
      CNQX of a small population of stratum radiatum interneurones of CA3 complicates
      interpretation of experiments designed to assess the consequences of blocking
      excitatory transmission with this drug.

PMID- 1360313
TI  - Mechanisms of cholecystokinin-induced protection of cultured cortical neurons
      against N-methyl-D-aspartate receptor-mediated glutamate cytotoxicity.
AB  - The protective effects of cholecystokinin (CCK) against glutamate-induced
      cytotoxicity were examined using cultured neurons obtained from the rat cerebral
      cortex. Cell viability was significantly reduced when the cultures were briefly
      exposed to glutamate or N-methyl-D-aspartate (NMDA) and then incubated with
      normal medium for 60 min. A 60-min exposure to kainate also reduced cell
      viability. CCK protected cortical neurons against glutamate-, NMDA- and kainate
      induced cytotoxicity. Glutamate- and NMDA-induced cytotoxicity was also reduced
      by N omega-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor. However, CCK
      did not prevent the cytotoxic effects of sodium nitroprusside (SNP) which
      spontaneously releases NO. Moreover, CCK did not affect NMDA-induced Ca2+ influx
      measured with rhod-2, a fluorescent Ca2+ indicator. Therefore, release of a NO
      like factor from the cerebral cortex was assayed using the thoracic artery in
      vitro. When the artery was incubated with minced cerebral tissues, glutamate
      elicited marked relaxation. SNP also elicited relaxation of the smooth muscle.
      CCK inhibited glutamate-induced relaxation but did not affect that induced by
      SNP. These results indicate that CCK prevents NMDA receptor-mediated cytotoxicity
      without reducing the Ca2+ influx. It is suggested that CCK inhibits NO-formation
      triggered by NMDA receptor activation.

PMID- 1360314
TI  - Inhibition of glutamate release in rat hippocampus by kynurenic acid does not
      protect CA1 cells from forebrain ischemia.
AB  - We assessed the effect of a broad spectrum glutamatergic receptor antagonist,
      kynurenic acid (500 mg/kg) on ischemia-induced hippocampal glutamate release and
      neuronal damage. Kynurenic acid significantly decreased glutamate release during
      ischemia but had no effect on the hippocampal lesion. Some protection was
      observed in the cortex and in the striatum. These data suggested that the
      extracellular accumulation of glutamate during forebrain ischemia does not play a
      major role in the hippocampus.

PMID- 1360315
TI  - Antagonism of limbic and extrapyramidal actions of intracerebrally injected
      dopamine by ergolines with partial D2 agonist activity in the rat.
AB  - Bromocriptine and a series of experimental ergoline D2 partial agonists (SDZ-208
      911, SDZ-212-327, SDZ-208-912) were evaluated for their interactions with
      exogenous dopamine (DA, at ED50 = 16 micrograms) stereotaxically injected
      unilaterally into a limbic (superior-medial nucleus accumbens septi) or
      extrapyramidal (central corpus striatum) target site in rat brain. Behavioral
      measures to quantify responses were locomotor arousal induced by DA in accumbens
      and contralateral head turning with striatum. All agents, given systemically
      (i.p.), induced dose-dependent inhibition of behavioral responses to DA from both
      brain sites. In both accumbens and striatum, SDZ-212-327 was most potent and
      bromocriptine, least; however, bromocriptine was relatively much more potent in
      accumbens, and SDZ-208-912 somewhat more potent in striatum. These results add to
      the growing impression that agents with partial agonist actions at central DA
      receptors can show behaviorally inhibitory effects that may reflect paradoxical
      antidopaminergic actions against the full, natural agonist of DA receptors and
      that such effects can be regionally selective.

PMID- 1360316
TI  - Immunohistochemical studies of noradrenergic-induced expression of c-fos in the
      rat CNS.
AB  - Previous studies have shown that stimulation of adrenergic receptors in the rat
      brain causes increased levels of mRNA of the immediate early gene, c-fos. The
      present studies were undertaken to determine if this stimulation also induces
      increased levels of c-fos immunoreactivity in the central nervous system (CNS).
      Rats were treated with the alpha-2 adrenoceptor blockers, yohimbine or
      atipamezole, or with restraint stress to activate central noradrenergic activity
      and were perfused 2 h later for immunohistochemical analysis of the cerebral
      cortex. Yohimbine, atipamezole and restraint stress each was found to cause
      increases in c-fos-like immunoreactivity (c-fos-li). Western blot analysis
      revealed increased c-fos protein in the cortex after yohimbine treatment. The c
      fos-li response to yohimbine was blocked by prior administration of the beta
      receptor antagonist, dl-propranolol, and to a lesser degree by the alpha-1
      antagonist, prazosin. It is concluded that adrenergic receptor stimulation in the
      cortex causes increased production of c-fos or fos related antigens and that this
      (these) immediate early gene product(s) may play a role in noradrenergic function
      in the CNS.

PMID- 1360318
TI  - Glutamate immunoreactive terminals in the lateral amygdaloid nucleus: a possible
      substrate for emotional memory.
AB  - The ultrastructure and synaptic associations of terminals immunoreactive for L
      glutamate (Glu) were examined in the lateral nucleus of the amygdala (AL). All
      results reported here involved tissue fixed only with paraformaldehyde. The
      specificity of the antiserum with paraformaldehyde fixation conditions was
      assessed and confirmed by immuno-dot blot analysis: the reactivity of anti-Glu to
      glutamic acid was at least 1,000 times greater than the reactivity to other amino
      acids. At the light microscopic level, Glu-immunoreactive punctate processes and
      somata were present in AL. At the electron microscopic level, many Glu
      immunoreactive terminals were identified. Data analysis was performed on 365 of
      these labeled terminals. Glu-immunoreactive terminals were 0.3-1.5 microns in
      diameter and contained numerous small, clear vesicles as well as mitochondria.
      Many (77%) of the terminals analyzed had morphologically identifiable synaptic
      specializations. Most (90%) of the Glu-immunoreactive terminals with synaptic
      specializations formed asymmetric synapses on spines or small dendrites; synaptic
      specializations on soma or proximal dendrites were rarely seen (< 1%). Glu
      immunoreactive terminals were qualitatively compared to terminals in AL labeled
      with two other antisera: anti-glutaminase, a marker for the enzyme that catalyzes
      the conversion of glutamine to the releasable or transmitter form of Glu, and
      anti-gamma-aminobutyric acid (anti-GABA), a marker for the major inhibitory amino
      acid transmitter in the brain. Terminals immunoreactive for glutaminase, like
      those immunoreactive for Glu, formed mostly asymmetric synaptic specializations
      on spines or small dendrites. In contrast, GABA-immunoreactive terminals usually
      formed symmetric synapses on soma or proximal dendrites and were never observed
      to form asymmetric axo-spinous contacts. Although Glu is a metabolic precursor to
      GABA, these data indicate that the majority of Glu-immunoreactive terminals
      reflect the site of synthesis and release of Glu and not of GABA. In addition,
      these results provide morphological evidence that Glu plays a role in excitatory
      neurotransmission at synapses in AL and support the growing body of data
      implicating excitatory amino acid-mediated synaptic plasticity in-emotional
      learning and memory processes in AL.

PMID- 1360319
TI  - The role of nerve growth factor in collateral reinnervation by cutaneous C-fibres
      in the rat.
AB  - We have investigated whether chronic nerve growth factor (NGF) depletion affects
      the development of transmedian collateral reinnervation by C-fibres. Using a dye
      labelled plasma extravasation technique in rats, the extent of transmedian
      innervation of the skin by C-fibres in the inferior alveolar nerve (IAN) was
      determined 8-10 weeks after sectioning and preventing regeneration of the
      contralateral IAN. Another group of animals were immunised against NGF prior to
      the nerve section and a third group acted as unoperated controls. A small but
      significant transmedian collateral reinnervation by C-fibres developed after
      contralateral denervation alone, but was not found in the animals also immunised
      against NGF. These results suggest that NGF is essential for the development of
      collateral reinnervation from cutaneous C-fibres.

PMID- 1360317
TI  - Do NMDA receptor antagonists protect against MPTP-toxicity? Biochemical and
      immunocytochemical analyses in black mice.
AB  - We investigated whether excitatory amino acids acting at the N-methyl-D-aspartate
      (NMDA) subtype of the L-glutamate receptor contribute to the dopaminergic
      neurotoxicity induced by systemic administration of the Parkinson's syndrome
      inducing toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl/6
      mice. The MPTP-regimen chosen (30-40 mg/kg body weight subcutaneously) resulted a
      60-70% depletion of striatal dopamine (DA) content and a 20% reduction of
      tyrosine hydroxylase immunoreactive (TH-IR) cells in the substantia nigra pars
      compacta 20 days after administration. Repeated systemic coadministration of the
      non-competitive NMDA receptor antagonist MK-801 or of the novel competitive NMDA
      receptor antagonist CGP 40116 did not protect against MPTP-induced striatal DA
      depletion 20 days after toxin administration. Additionally, no short-term
      protective effects of MK-801 on striatal DA content were observed 24, 48, and 96
      h, respectively, after exposure to MPTP. A slight and non-significant attenuation
      (approximately 10%) of the MPTP-induced decrease in the number of nigral TH-IR
      cells was observed after MK-801- and CGP 40116-treatment. We conclude that
      neurotoxicity of systemically administered MPTP is not substantially antagonized
      by NMDA receptor antagonists in mice.

PMID- 1360320
TI  - Dissociation of mu and delta opioid receptor-mediated reductions in evoked and
      spontaneous synaptic inhibition in the rat hippocampus in vitro.
AB  - Modulation of gamma-aminobutyric acid (GABA)-mediated inhibition, and glutamate
      mediated excitation by highly selective mu and delta opioid agonists was studied
      using intracellular recordings of CA1 pyramidal neuron synaptic responses in
      superfused hippocampal slices. Equimolar concentrations of the selective mu
      agonist, [Tyr-(D-Ala)-Gly-(N-Me-Phe)-Gly-ol]-enkephalin (DAGO), or the delta
      selective agonist, [D-Pen2,D-Pen5]-enkephalin (DPDPE), reversibly increased the
      amplitudes of excitatory post-synaptic potentials (EPSPs), evoked by Schaffer
      collateral/commissural stimulation, without altering the input resistance or
      resting membrane potential of these CA1 pyramidal neurons. The increased EPSP
      amplitudes resulting from superfusion with the enkephalin analogs were
      qualitatively similar to those caused by the GABAA receptor antagonist,
      bicuculline methiodide (BMI). Specific stimulation/recording protocols and micro
      lesions of the slices were used to evoke relatively pure forms of recurrent and
      feed-forward GABA-mediated inhibitory post-synaptic potentials (IPSPs). The mu
      opioid agonist DAGO reduced both recurrent and feed-forward IPSPs, while the
      delta agonist DPDPE had no effect upon these responses. To test the hypothesis
      that the enhancement of pyramidal neuron EPSPs by delta (and mu) opioids was due
      to the reduction of an inhibitory potential that was coincident with the EPSP,
      DPDPE or the mu agonist, DAGO, were applied while recording monosynaptic IPSPs
      following the elimination of EPSPs by the glutamate receptor antagonists, D,L-2
      amino-5-phosphonovalerate (APV) and 6,7-dinitroquinoxaline-2,3-dione (DNQX). The
      mu agonist, DAGO, reversibly reduced these pharmacologically isolated IPSPs,
      while the delta agonist, DPDPE, had no effect upon these responses. Despite the
      fact that the delta agonist, DPDPE, had no effect on recurrent, feed-forward or
      monosynaptic evoked IPSPs, this enkephalin did reversibly reduce the frequency of
      spontaneously occurring IPSPs, measured using whole-cell recordings with pipettes
      containing 65 mM KCl. The mu agonist, DAGO, and the GABAA antagonist, BMI,
      similarly reduced spontaneous IPSP rates. We conclude from these data that mu and
      delta opioid receptor activation increases EPSPs via the reduction of a form of
      GABAergic inhibition that is difficult to characterize, and which may be distinct
      from conventional feed-forward and recurrent inhibition. Furthermore, delta
      opioids seem to reduce this form of GABAergic inhibition selectively, while mu
      opioids reduced this inhibition, and conventional feed-forward and recurrent
      IPSPs as well.

PMID- 1360321
TI  - Synergistic and persistent interaction between the D2 agonist, bromocriptine, and
      the D1 selective agonist, CY 208-243.
AB  - In mice pretreated with reserpine and alpha-methyl-DL-p-tyrosine (alpha MPT) to
      deplete central catecholamines, the D2 dopamine receptor-selective agonist,
      bromocriptine, at a dose of 10 mg/kg produced no locomotor activity. The D1
      selective agonist, CY 208-243, generated a dose-dependent locomotor response in
      this animal model for Parkinson's disease; low doses elicited little or no effect
      while higher doses resulted in a short burst of locomotor activity (2 h). The
      combination of CY 208-243 and bromocriptine had a dramatic synergistic effect on
      locomotion. Most importantly, this combination of D1 and D2 agonists converted a
      brief (2 h) effect on locomotion to one which persisted for up to 6 h. These
      results suggest that the combination of D1 and D2 dopamine receptor agonists can
      affect both the intensity and the persistence of a locomotor response.

PMID- 1360322
TI  - Trans-ACPD-induced phosphoinositide hydrolysis and modulation of hippocampal
      pyramidal cell excitability do not undergo parallel developmental regulation.
AB  - The selective metabotropic glutamate receptor agonist, trans-1-aminocyclopentane
      1,3-dicarboxylic acid (trans-ACPD), stimulates phosphoinositide hydrolysis and
      elicits a number of electrophysiological responses in the hippocampus. If these
      effects are mediated by the same receptor subtype, they should undergo parallel
      developmental regulation. Therefore, we compared the phosphoinositide hydrolysis
      response and the electrophysiological responses to trans-ACPD at two different
      developmental stages. Trans-ACPD-stimulated phosphoinositide hydrolysis was
      significantly greater in hippocampal slices from immature (6-11-day-old) rats
      than from adults. In contrast, trans-ACPD elicited decreases in spike frequency
      adaptation and in the amplitude of the slow afterhyperpolarization in roughly
      equal percentages of immature and adult CA1 pyramidal cells. Similar results were
      obtained using the putative endogenous agonist, glutamate. These data support the
      hypothesis that certain electrophysiological effects of trans-ACPD are mediated
      by a metabotropic glutamate receptor that is distinct from the phosphoinositide
      hydrolysis-linked glutamate receptor.

PMID- 1360323
TI  - NMDA receptors in the nucleus accumbens modulate intravenous cocaine but not
      heroin self-administration in the rat.
AB  - The role of endogenous glutamate neurotransmission within the nucleus accumbens
      in the modulation of intravenous (i.v.) cocaine and heroin self-administration in
      rats was analyzed. APV (2-amino-5-phosphonovaleric acid), a blocker of glutamate
      receptors of the N-methyl-D-aspartate (NMDA) type, was microinfused within the
      nucleus accumbens of the ventral striatum of rats trained to lever press for i.v.
      cocaine or heroin self-administration. APV, at the dose of 1.5 and 3.0
      micrograms/side, reduced the rewarding value of cocaine while it left heroin self
      administration unaffected. These results suggest that integrity of NMDA receptor
      function within the nucleus accumbens may be of importance for the maintenance of
      i.v. cocaine, but not heroin self-administration in rats.

PMID- 1360324
TI  - Sustained enhancement of NMDA receptor-mediated synaptic potential by
      isoproterenol in rat amygdalar slices.
AB  - The effect of isoproterenol (Iso) on synaptic transmission mediated by the N
      methyl-D-aspartate (NMDA) receptors (EPSPNMDA) was investigated in slices of rat
      amygdala using intracellular recording techniques. EPSPNMDA was isolated
      pharmacologically by application of a solution containing the non-NMDA receptor
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and GABAA
      receptor blocker bicuculline (20 microM). Superfusion of Iso (15 microM) produced
      a long-lasting enhancement of EPSPNMDA. Pretreatment the slices with propranolol
      (10 microM) completely prevented the effect of Iso confirming the mediation by
      beta-adrenergic receptors. These results provide the direct evidence for
      adrenergic modulation of excitatory amino acid neurotransmission in the
      vertebrate central nervous system.

PMID- 1360325
TI  - Regional distribution of glutamate and aspartate in adult and old human brain.
AB  - In previous studies on rat brain we found that the observed heterogeneity of the
      regional distribution of amino acids was much greater when small well-defined
      anatomical structures were assayed. We therefore reinvestigated the distribution
      of glutamate and aspartate in 50 discrete areas from adult and old human brain.
      The concentration of glutamate in the area of highest level was 4.5 and 4.7 times
      as high as in the area of lowest level in adult and old brain respectively; for
      aspartate these values were 3.0 and 6.6. Several changes in old brain were noted.
      The human pattern differed from that in rat.

PMID- 1360326
TI  - Pharmacological characterization of lower esophageal sphincter relaxation induced
      by swallowing, vagal efferent nerve stimulation, and esophageal distention.
AB  - To characterize the neural pathways involved in lower esophageal sphincter
      relaxation, intraluminal pressures from the lower esophageal sphincter of the
      opossum were monitored during swallowing, vagal efferent nerve stimulation, and
      intraluminal balloon distention in the presence and absence of pharmacologic
      antagonism of putative neurotransmitters. The combination of atropine,
      hexamethonium, and 5-methoxydimethyltryptamine, which is known to block
      ganglionic transmission in the vagal inhibitory pathway to the lower esophageal
      sphincter, significantly antagonized LES relaxation induced by both swallowing
      and vagal stimulation, but did not affect the LES relaxation induced by balloon
      distention. Administration of the nitric oxide synthase inhibitor N omega nitro-L
      arginine methyl ester, on the other hand, markedly inhibited LES relaxation
      induced by vagal stimulation, swallowing, and balloon distention, and this effect
      was reversed by administration of the nitric oxide synthase substrate L-arginine.
      These studies indicate that the distension-induced intramural pathway mediating
      LES relaxation does not involve ganglionic transmission similar to that of the
      vagal inhibitory pathway to the LES. However, the LES relaxation induced by all
      forms of stimuli appears to depend on nitric oxide as a final mediator.

PMID- 1360327
TI  - Expression of the HER-2/neu proto-oncogene in serous ovarian neoplasms.
AB  - BACKGROUND: It is unclear whether HER-2/neu proto-oncogene expression in ovarian
      epithelial neoplasms is related to prognosis. METHODS: The authors performed
      immunohistochemical stains on 20 serous tumors of low malignant potential (STLMP)
      in Stages I and II and 19 serious carcinomas in the same stages. They used three
      different commercial antibodies to make comparisons. RESULTS: Two of four Stage I
      STLMP in patients who experienced disease progression showed positive staining
      for the gene product, whereas none of seven Stage I nonprogressive STLMP showed
      positive staining. Five of the six Stage III nonprogressive STLMP showed positive
      staining, whereas none of three Stage III STLMP that progressed showed positive
      staining. Three carcinomas (one Stage I and two Stage III) also showed positive
      staining. CONCLUSIONS: Expression of HER-2/neu may be associated with high stage
      in serous ovarian neoplasms, but it is not likely to identify the small fraction
      of patients with STLMP who will experience disease progression.

PMID- 1360329
TI  - Dual colour flow cytometry of p53 and c-erbB-2 expression related to DNA
      aneuploidy in primary and metastatic breast cancer.
AB  - DNA aneuploidy and p53 or c-erbB-2 expression were simultaneously measured in 29
      breast tumours by two-colour flow cytometry. (i) The majority of tumours had some
      cells expressing either p53 (5-68%) or c-erbB-2 (1-56%). (ii) Expression of p53
      and c-erbB-2 was observed mainly in the aneuploid population of mixed aneuploid
      and diploid tumours but there was no significant correlation with a specific DNA
      index. Aneuploid tumours contained higher percentages of c-erbB-2 positive cells
      (average 25%) than purely diploid tumours (average 15%) but this just failed to
      reach significance (P = 0.074). No relevant trends were noted for p53 expression.
      (iii) Significantly increased c-erbB-2 expression was observed in stage 2 tumours
      (26%) compared to stage 1 tumours (12%) (P = 0.001) with no trend evident for p53
      expression. (iv) The metastatic tumour in the axillary node contained similar or
      slightly higher percentages of positive cells than the matched primary tumour.

PMID- 1360328
TI  - Characterization of a B-cell immunodominant epitope of human T-lymphotropic virus
      type 1 (HTLV-I) envelope gp46.
AB  - The immune response elicited by a synthetic peptide derived from an
      immunodominant external envelope region (Env-5, amino acids 242-257) of human T
      lymphotropic virus type 1 (HTLV-I) was tested in a rabbit model of HTLV-I
      infection. The synthetic peptide elicited a strong antibody response to the HTLV
      I envelope protein gp46; however, these antibodies failed to inhibit HTLV-I
      mediated cell fusion. Immunized rabbits were not protected from HTLV-I infection
      as determined by seroconversion to viral core proteins by immunoblot, HTLV-I p24
      antigen detection in lymphocyte cultures and polymerase chain reaction for the
      HTLV-I provirus in lymphocyte DNA. Env-5 peptide immunization failed to induce T
      cell lymphocyte proliferative responses in rabbits, but induced antibody
      responses in T-cell deficient Balb c nu/nu mice suggesting that the antigenic
      determinant represented by the Env-5 peptide is primarily a B-cell epitope. These
      results further define an immunodominant epitope of the HTLV-I envelope protein
      and suggest that potential synthetic peptide vaccines against HTLV-I infection
      must contain multiple antigens that induce both humoral and cellular immune
      reactivity.

PMID- 1360330
TI  - Anticarcinogenic action of diallyl sulfide in hamster buccal pouch and
      forestomach.
AB  - The anticarcinogenic action of the garlic constituent diallyl sulfide (DAS), was
      examined in the hamster buccal pouch and forestomach. Groups of hamsters were
      topically treated, for up to 14 weeks, with a 0.5% solution of the buccal pouch
      and forestomach carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Prior to,
      during and after DMBA treatment, groups of hamsters were also treated, on
      alternate days, with a 1% solution of DAS. In addition to tumor formation, the
      induction of gamma-glutamyl transpeptidase (gamma GT) buccal pouch epithelial
      lesions served as an additional presumptive index of in vivo
      carcinogenesis/anticarcinogenesis. DAS resulted in a significant reduction in
      buccal pouch tumor frequency, buccal pouch tumor burden, buccal pouch gamma GT
      lesion frequency and forestomach tumor frequency. In a separate experiment, DAS
      also reduced the level of autoradiographically quantified unscheduled DNA repair
      synthesis (UDS) in pieces of hamster buccal pouch concurrently exposed in vitro
      to the potent buccal pouch carcinogen N-methyl-N-benzylnitrosamine (MBN). This
      study demonstrates that DAS is an effective anticarcinogenic agent in squamous
      mucosa of the hamster and suggests novel cost-effective strategies for the rapid
      identification of tissue-specific anticarcinogens and a quantitative assessment
      of their efficacy.

PMID- 1360331
TI  - Clinical outcome of acute myocardial infarction in patients on treatment with
      beta-blockers or calcium antagonists. A study of 7,922 hospitalized first
      myocardial infarctions.
AB  - To assess the effects of current treatments with beta-blockers or calcium
      antagonists on the clinical outcome of acute myocardial infarction (MI),
      enzymatically estimated infarct sizes, circulatory arrests from ventricular
      tachyarrhythmias, ventricular tachycardia (VT)/ventricular fibrillation (VF), and
      in-hospital mortality were analyzed retrospectively from 7,922 citizens of Malmo,
      Sweden, hospitalized due to a first MI between 1973 and 1987. Of these patients,
      296 were on treatment with calcium antagonists, 393 on treatment with a beta 1
      selective beta-blocker, 482 with a nonselective beta-blocker, and 95 on combined
      treatment with beta-blockers and calcium antagonists at the time of admission to
      hospital. In a set of multivariate analyses including several clinical
      characteristics, patients on treatment with a nonselective beta-blocker had a
      significantly lower peak aspartate aminotransferase (ASAT; difference -0.70
      mukat/l, 95% CL: -1.24 to -0.16), whereas no significant relations between peak
      ASAT and treatment with cardioselective beta-blockers or calcium antagonists were
      found. Treatment with cardioselective beta-blockers or calcium antagonists, in
      contrast to treatment with a nonselective beta-blocker, were significant
      predictors of the occurrence of circulatory arrests from VT/VF. The relative risk
      of VT/VF in patients on cardioselective beta-blockers was 1.51 (95% CI: 1.12
      2.03), and in patients on calcium antagonists 1.44 (95% CI: 1.03-2.02). None of
      the treatments were significantly associated with in-hospital mortality. In
      patients on beta-blockers or calcium antagonists when suffering their first MI,
      nonselective beta-blockade may reduce infarct size. Treatment with beta-blockers
      or calcium antagonists identified patients with an increased risk of circulatory
      arrests from VT/VF, but neither of the treatments were significantly associated
      with in-hospital mortality. We suggest that only minor differences exist between
      the effects of chronic treatment with beta-blockers and calcium antagonists on
      the outcome of an acute MI.

PMID- 1360333
TI  - Rapid pacing heart failure.

PMID- 1360332
TI  - beta Adrenergic receptor desensitisation may serve a cardioprotective role.
AB  - OBJECTIVE: The aim was to test the hypothesis that beta adrenoceptor
      desensitisation is a form of cardioprotection whereby the myocardium is protected
      from the injurious effects of excessive adrenergic stimulation by isoprenaline.
      METHODS: A new sensitive and specific method of identifying cardiac myocyte
      necrosis with monoclonal antimyosin was employed. Antibody labelled necrotic
      cardiomyocytes from male Sprague-Dawley rats (190-300 g) were identified by
      immunofluorescence. Homologous beta adrenoceptor desensitisation was induced by 9
      d pretreatment with isoprenaline infusion (20 mg.kg-1.d-1), and heterologous
      desensitisation by treatment with 0.15% propylthiouracil in the diet for six
      weeks. The effects of isoprenaline induced cardiomyocyte injury in these animals
      were compared with those in control rats. RESULTS: In euthyroid control rats,
      treatment with the beta adrenergic agonist, isoprenaline, produced prolonged
      tachycardia and hypotension, and a significant amount of cardiac myocyte necrosis
      subendocardially. When the same isoprenaline challenge was given to rats
      pretreated for 9 d with an isoprenaline infusion, the haemodynamic response was
      markedly attenuated and very little myocyte necrosis was noted. In the model of
      heterologous desensitisation occurring in hypothyroidism, isoprenaline challenge
      produced markedly diminished haemodynamic response and little cardiac myocyte
      necrosis. CONCLUSIONS: In both homologous and heterologous models of beta
      adrenoceptor desensitisation, the susceptibility of the myocardium to
      isoprenaline induced cytotoxicity is markedly reduced.

PMID- 1360334
TI  - Vascular atrial natriuretic factor receptors in spontaneously hypertensive rats.
AB  - OBJECTIVE: The aim was to investigate vascular receptors for atrial natriuretic
      factor (ANF) in spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar
      rats (WR) at different ages. METHODS: Relaxation and guanylate cyclase responses
      of blood vessels to atrial natriuretic factor were investigated, as was the
      binding of 125I-ANF to vascular membranes and ANF receptor subtypes, using sodium
      dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in reducing
      conditions, after solubilisation and irreversible binding of 125I-ANF. RESULTS:
      Vascular relaxation responses of aorta showed an increased sensitivity to ANF in
      four week old SHR [pD2 = 8.9 (SEM 0.1) v 8.5(0.1) in WKY rats, p < 0.05] while
      sensitivity was similar for the three strains at older ages. Production of cyclic
      GMP in mesenteric arteries in response to 100 nmol.litre-1 ANF was greater (p <
      0.05) in SHR than in WKY rats at four weeks of age, but was similar in older
      rats. The density of binding sites for ANF in mesenteric arteries, however, was
      lower in SHR at four weeks (p < 0.01), and increased in older rats, becoming
      similar to that of normotensive rats at 12 weeks of age. Affinity of ANF sites
      was similar in all strains. The proportion of high and low molecular weight ANF
      binding peptides in solubilised blood vessel membranes on SDS-PAGE was similar in
      all strains except in four week old SHR, in which binding to the high molecular
      weight band (presumably the guanylate cyclase containing receptor) was increased
      relative to the low molecular weight band (non-cyclase-coupled receptor) in
      comparison to other strains and ages. CONCLUSIONS: Activity of guanylate cyclase
      in response to occupancy of ANF receptors may be increased in young SHR. Normal
      relaxation of blood vessels in response to ANF in older SHR could result in
      failure to counteract the increased vasoconstrictor activity present in these
      rats, which could play a role in the increase in blood pressure.

PMID- 1360335
TI  - Catecholaminergic cells and fibers in the brain of the lizard Anolis carolinensis
      identified by traditional as well as whole-mount immunohistochemistry.
AB  - Using traditional as well as whole-mount immunohistochemistry, we described the
      location of tyrosine hydroxylase- and dopamine beta hydroxylase-positive cells
      and fibers in the brain of the lizard Anolis carolinensis. Major
      catecholaminergic cell groups were in the ependyma in certain ventricular
      regions, along the periventricular floor in the preoptic region, within the
      anterior hypothalamic and lateral hypothalamic areas, and in the mesencephalic
      tegmental region, locus coeruleus, nucleus of the solitary tract, vagal motor
      nucleus, and rhombencephalic reticular formation. Major catecholaminergic fibers,
      tracts and varicosities included tuberohypophysial, mesolimbic, nigrostriatal,
      isthmocortical, medullohypothalamic, and coeruleospinal systems. Although the
      catecholaminergic systems in A. carolinensis are similar to those in the brains
      of other lizards studied, there are a few species differences. Our information
      about A. carolinensis will be used to help localize the hypothalamic asymmetry in
      catecholamine metabolism previously described in this lizard.

PMID- 1360336
TI  - Role of CD11a/CD18-CD54 interactions in suppression of human B cell
      responsiveness by CD4+ suppressor T cells.
AB  - The role of leukocyte function-associated Ag-1 (LFA-1, CD11a/CD18) and
      intercellular adhesion molecule 1 (ICAM-1, CD54) interactions in the suppression
      of human B cell function by immobilized anti-CD3-activated CD4+ T cells was
      examined by studying the effects of mAb to these determinants. The suppressive
      activity was assessed by the effects of CD4+ T cells without mitomycin C
      treatment activated by immobilized anti-CD3 for 72 hr on the differentiation into
      Ig-secreting cells of B cells activated for 72 hr with immobilized anti-CD3
      stimulated CD4+ T cells that had been treated with mitomycin C (T4 mito).
      Suppression was not observed when activated CD4+ T cells and B cells were
      separated by filter membranes, indicating that the suppression requires the
      direct interactions between anti-CD3-activated CD4+ T cells and activated B
      cells. In this model system, mAb to either the alpha (CD11a) or beta (CD18) chain
      of LFA-1 or ICAM-1 (CD54) reversed the suppression of B cell function by
      suppressor CD4+ T cells significantly. Reversal of suppression of B cell function
      was most marked when activated B cells were treated with mAb to ICAM-1 and
      suppressor CD4+ T cells were treated with mAb to LFA-1, but not vice versa.
      Studies using fluorescence-activated cell sorter revealed marked increase of
      expression of ICAM-1 on B cells after 72 hr of activation with immobilized anti
      CD3-stimulated T4 mito. These results indicate that the interactions between LFA
      1 and ICAM-1 play an important role in mediating the suppressive activity of anti
      CD3-activated CD4+ T cells to B cells. Moreover, the data are consistent with a
      model of T-cell-mediated B cell suppression in which interactions between LFA-1
      on suppressor T cells and ICAM-1 on activated B cells play a central role in the
      suppression of B cell function.

PMID- 1360337
TI  - Continuous infusions of atracurium and vecuronium, compared with intermittent
      boluses of pancuronium: dose requirements and reversal.
AB  - This study was designed to determine the effect of prolonged infusion on the ease
      of reversal of atracurium and vecuronium, and whether factors which potentiate
      the block delayed reversal. In phase one, 40 patients were randomized (double
      blind) to determine the steady state conditions for atracurium and vecuronium.
      Fourteen atracurium patients and 17 vecuronium patients were evaluable. The
      unblinded second phase involved the steady state conditions using halothane or
      isoflurane and atracurium infusions. The infusion required for 95% twitch
      depression (TD95) for atracurium was 7.6 +/- 1.1 micrograms.kg-1 x min-1. The
      requirement for vecuronium changes with time: TD95 at 30 min was 1.01 +/- 0.16,
      at 60 min 0.89 +/- 0.12 and after 90 min 0.85 +/- 0.17 micrograms.kg-1 x min-1 (P
      < 0.05). The mean TD95 was 0.94 +/- 0.23 micrograms.kg-1 x min-1. Multivariate
      regression analysis of the infusion data revealed a vecuronium model predicting
      TD95 by the duration of infusion (P < 0.05) and weight (P = 0.05). Atracurium
      TD95 was predicted by age (P = 0.05). The addition of an inhalation agent to
      atracurium reduced the infusion rate by 2.01 +/- 0.28 micrograms.kg-1 x min-1 (P
      = 0.0001) for each increase in MAC. The mean reversal times for atracurium with
      three different anaesthetics and for vecuronium were not different. Reversal of
      pancuronium blockade, from less profound twitch depression (86.4 vs 95%) took
      twice as long as for atracurium and vecuronium for which the following predictors
      were identified: age, weight, duration of infusion, level of blockade, and type
      of anaesthetic, using a stepwise regression model.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1360338
TI  - Postoperative analgesia: opioid infusions in infants and children.
AB  - The purpose of this review is to emphasise the ineffectiveness of traditional
      analgesic therapy in paediatric patients after surgery, to examine the sensation
      of pain in infants and children, and to describe the use of intravenous opioids
      for postoperative analgesia. The management of acute postoperative pain in the
      paediatric surgical population has been poor. This is despite the knowledge that
      infants and children have sufficient neurological development at birth to sense
      pain, and that the same hormonal and metabolic responses to nociceptive stimuli
      that occur in adult also occur in the neonate. Physicians frequently order
      analgesics in inappropriate doses, nurses are reluctant to administer opioids,
      and children themselves frequently compound the problem by refusing injections.
      The sophisticated techniques for providing postoperative analgesia which have
      been used so successfully in adults can also be used in paediatric patients. Two
      of these, continuous intravenous opioid infusion and patient-controlled
      analgesia, have proved to be very successful. Children older than six months can
      receive either modality safely with regular monitoring by qualified nursing
      staff. Infants younger than six months receiving continuous opioid infusions
      should be monitored in high-dependency units.

PMID- 1360339
TI  - Epinephrine augments von Willebrand factor-dependent shear-induced platelet
      aggregation.
AB  - BACKGROUND: Shear-induced platelet aggregation (SIPA) is an important mechanism
      in thrombogenesis. von Willebrand factor (vWF) binding to platelet glycoprotein
      Ib (GP Ib) has been found to be crucial for platelet aggregation under the high
      shear force probably generated in stenosed coronary artery. The physiological
      significance of vWF-dependent SIPA has not been clarified. METHODS AND RESULTS:
      Blood samples were collected from 23 normal volunteers. SIPA was continuously
      monitored using a modified cone-plate viscometer adapted for measuring the
      transmitted light intensity of the material. The effects of low concentrations of
      epinephrine, ADP, and collagen on SIPA under both low shear (12 dyne/cm2) and
      high shear (108 dyne/cm2) force were investigated. All agonists tested enhanced
      SIPA under low shear force, whereas only epinephrine augmented SIPA under high
      shear force. The maximum extents of SIPA under high shear force in the absence
      and presence of epinephrine (10 ng/ml) were 37.9 +/- 11.5% and 59.7 +/- 13.9%,
      respectively. The antagonist of the alpha 2-adrenergic receptor yohimbine (1
      microgram/ml) antagonized the effects of epinephrine. The monoclonal antibody NMC
      4 against vWF, which was shown to inhibit its binding to GP Ib, completely
      abolished SIPA under high shear force, even in the presence of epinephrine.
      However, this antibody only partially inhibited SIPA under low shear force.
      CONCLUSIONS: Our findings suggest that epinephrine is the agonist that enhances
      SIPA mediated by vWF through its specific receptor. This may be clinically
      important because occlusion of the coronary artery often occurs in stenosed
      atherosclerotic vessels under sympathetic stimulation.

PMID- 1360340
TI  - Lymphocyte subsets in HTLV-II-infected former blood donors: relationship to
      spontaneous lymphocyte proliferation.
AB  - Previous studies showed that over 70% of HTLV-seropositive blood donors from the
      Los Angeles area are infected with HTLV-II; further, mononuclear cells from about
      half of these HTLV-II+ donors exhibit spontaneous lymphocyte proliferation (SLP)
      during in vitro culture. To determine if HTLV-II+SLP+ donors exhibit more marked
      immune system changes than HTLV-II+SLP- donors, lymphocyte subsets for these two
      HTLV-II+ groups were compared to an uninfected control group. The percentage of
      lymphocytes expressing CD3 was significantly increased and the percentage
      expressing a CD16/56+CD3- phenotype (natural killer cells) was significantly
      decreased in the HTLV-II+SLP+ group (N = 34) versus the control group (N = 49).
      On the basis of absolute numbers, the lymphocyte number was significantly higher
      in the HTLV-II+SLP+ group than in the control group and reflected significant
      increases in the numbers of both CD4 and CD8 subsets of T cells. Analysis of
      proportional changes in CD4 and CD8 cell subsets revealed significant increases
      in the proportions of CD4 cells expressing HLA-DR, CD8 cells expressing HLA-DR,
      and CD8 cells expressing CD45RO for the HTLV-II+SLP+ group versus the control
      group. For all phenotypic parameters measured, no significant differences were
      noted when comparing the HTLV-II+SLP- group (N = 21) and the control group. Cell
      culture experiments utilizing purified CD4 cells and CD8 cells from a subset of
      each study group revealed that in vitro spontaneous proliferative capacity
      resides within both the CD4 cell and CD8 cell populations from SLP+ individuals.
      These findings show that changes in circulating lymphocyte subsets in HTLV-II
      infection are found only in association with SLP, and that the capacity to
      exhibit SLP characterizes both CD4 and CD8 lymphocyte subsets.

PMID- 1360343
TI  - Race, ethnicity, and the propensity for neonatal jaundice. Introduction.

PMID- 1360341
TI  - The role of T-cell subsets in the response to anti-CD3 monoclonal antibodies.
AB  - Administration of monoclonal antibodies (mAb) to CD3 elicits an immune response
      to the mAb and an acute toxic syndrome that has been attributed to the release of
      cytokines from activated T cells. To clarify the cellular basis for these
      effects, we used anti-lymphocyte mAb to deplete selected T-cell subsets from
      BALB/c mice prior to administration of anti-CD3. In our first series of
      experiments, anti-CD4 repeatedly blocked the immune response to anti-CD3, but did
      not prevent severe toxicity. This observation suggested that other T-cell subsets
      might contribute to anti-CD3 induced toxicity. Therefore, we treated mice with
      mAb to CD8 as well as mAb to CD4 prior to administration of anti-CD3. Despite
      depletion of > 95% of CD8+ and CD4+ T cells, toxicity was not suppressed. This
      finding cast doubt on the belief that toxicity is due to activation of either
      CD4+ or CD8+ T cells by anti-CD3. Therefore, we assessed the role of thymocytes
      (which are not deleted by the mAb) and gamma delta + T cells. Thymectomy did not
      prevent toxicity in CD4/CD8-depleted mice, demonstrating that thymocytes are not
      responsible for toxicity. Anti-alpha beta TCR mAb produced a toxic reaction
      similar to anti-CD3 whereas anti-gamma delta TCR mAb did not, suggesting that
      gamma delta+ T cells are not the source of toxic cytokines. In addition, we
      proved that anti-CD3-induced toxicity was not due to direct effects on
      macrophages or to other nonspecific factors associated with the hamster mAb.
      These findings imply that a few residual mature T cells in mice treated with mAb
      to CD4 and CD8 are sufficient for the full expression of the anti-CD3-induced
      toxic syndrome. To confirm that both CD4+ and CD8+ T cells can mediate toxicity,
      we showed that:(i) SCID mice, which normally do not develop anti-CD3-induced
      toxicity, can be rendered susceptible by reconstitution with purified CD4+ T
      cells; and (ii) CD4-knockout mice that lack CD4+ T cells but have normal CD8+ T
      cells are susceptible to anti-CD3-induced toxicity. These findings establish that
      both CD4+ and CD8+ cells contribute to the toxic effects of anti-CD3, and that
      relatively few cells are required to mediate the full effect.

PMID- 1360342
TI  - Induction of intercellular adhesion molecule-1 (CD54) on isolated mouse
      pancreatic beta cells by inflammatory cytokines.
AB  - Insulin-dependent diabetes mellitus (IDDM) results from a T cell-dependent
      autoimmune destruction of insulin-producing pancreatic beta cells. In the present
      study, expression of adhesion molecule ICAM-1 (CD54) on pancreatic beta cells was
      studied in normal, obese hyperglycemic (ob/ob), and nonobese diabetic (NOD) mice.
      Freshly isolated pancreatic beta cells from ob/ob mice did not express ICAM-1,
      but treatment of the cells with IL-1-beta, TNF-alpha, or INF-gamma strongly
      induced its expression as measured by immunofluorescence flow cytometry. The
      cytokines acted in a dose- and time-dependent manner. Maximal induction by either
      cytokine occurred at 24 hr and thereafter expression decreased, except for INF
      gamma. Immunoprecipitation from IL-1-beta-treated beta cells demonstrated a cell
      surface glycoprotein with an apparent molecular weight of 95 kDa. ICAM-1
      expression was undetectable on pancreatic beta cells of normal and ob/ob mice as
      measured by immunohistochemistry. In NOD mice at different ages (1 to 6 months)
      ICAM-1 was also undetectable on beta cells, in contrast to the strong expression
      on infiltrating mononuclear cells. The present study indicates that mouse
      pancreatic beta cells, under certain conditions, can express ICAM-1.

PMID- 1360344
TI  - Non-physician medical care.

PMID- 1360345
TI  - The modes of action of spider toxins on insects and mammals.

PMID- 1360346
TI  - Effects of arginine vasotocin on cardiorespiratory and thermoregulatory responses
      in the pigeon.
AB  - 1. The effects of intramuscular injections (10 ng, 100 ng, 1 mu or 10 mu/pigeon)
      of two preparations of synthetic arginine vasotocin (AVT), deamino-dicarba
      arginine vasotocin (ddAVT) and arginine vasotocin diacetate tetrahydrate (AVTdt)
      on heart rate (HR), breathing frequency (BF), oxygen consumption (VO2), cloacal
      and foot temperatures (Tc and Tf) and shivering (S) were studied in the pigeon
      housed in a respiratory flow chamber maintained at a temperature of 22.5 degrees,
      during a 4 hr post-injection period. 2. In general, with the exception of the
      lowest dose, AVT-treatment produced hypothermic responses, as was indicated by Tc
      and Tf. 3. Both ddAVT and AVTdt produced increases in HR and BF when administered
      in high concentrations (10 micrograms/pigeon), the effect being more potent with
      AVTdt than ddAVT; with lower doses, the effects were considerably less
      pronounced. This increase in HR and BF is attributed to a probable compensatory
      response to the hypothermic effect. 4. With a 10 micrograms dose, ddAVT produced
      a greater decline in VO2 than AVTdt. Although other doses too evoked a drop in
      VO2 at certain post-injection time points, the effect was of lesser magnitude. 5.
      No significant shivering response was elicited, in spite of the drop in Tc. 6. It
      is suggested that, besides the antidiuretic function of AVT, its hypothermic
      effect would be of considerable importance in thermal homeostasis during flight
      in birds.

PMID- 1360347
TI  - Trace metal (Cu and Zn) adaptation of organ systems of the American eel, Anguilla
      rostrata, to external concentrations of cadmium.
AB  - 1. The impact of external cadmium on the concentrations of cadmium (Cd), copper
      (Cu) and zinc (Zn) in seven tissues of the American eel, Anguilla rostrata was
      investigated. Even after a week in freshwater with undetectable levels of Cd, the
      tissues of eels caught in fresh and/or brackish waters of the United States east
      coast contained Cd in kidney, liver, gut, and brain. 2. When the eels were
      exposed up to 16 weeks to low and high sublethal concentrations of Cd (75 and 150
      micrograms/l, respectively), the highest tissue concentrations of Cd were found
      after two weeks of exposure. The accumulation was dose-related in all tissues
      studied except for the kidney. After 8 weeks of Cd exposure, the tissue levels of
      Cd were markedly reduced, and they were in a similarly low range after 16 weeks.
      At this time, the highest Cd concentrations were found in the gills and kidney.
      3. After two weeks of Cd exposure, there was a drop of the tissue concentrations
      of Cu in liver and heart, and of Zn in gut and liver. The low concentrations of
      the two metals in other organs did not allow an evaluation of the Cd impact.
      After 16 weeks, the Cu concentrations in all tissues, with the exception of the
      liver, were similar to, or even higher than control levels. At the same time, Zn
      concentrations exceeded the control levels in heart and kidney of eels exposed to
      75 and 150 micrograms Cd/l, respectively. 4. It is clear that some tissues of the
      eel are able to maintain or restore normal levels of Cu and Zn, up to 16 weeks,
      despite concomitant Cd accumulation.

PMID- 1360348
TI  - Inhibition of eggshell formation in domestic fowl by indomethacin: relation to
      calcium and prostaglandin metabolism in the eggshell gland mucosa.
AB  - 1. The involvement of prostaglandins in eggshell formation in the domestic fowl
      was investigated by considering the effects of the drug indomethacin on the
      calcium metabolism on the eggshell gland. Egglaying birds were given a single
      dose (100 mg) of indomethacin at the beginning of shell calcification. Fourteen
      hours later the birds were sacrificed and the effects of the drug were
      determined. There was a 21% reduction in the shell thickness of the egg present
      in the shell gland at the time of slaughter (P < 0.01). The calcium content of
      the eggshell gland mucosa was increased to 153% (P < 0.01) of the controls. In
      the treated birds, there was 43% more calcium (P < 0.05) present in the shell
      gland lumen (recovered by rinsing with Tris buffer) than in the gland lumen of
      control birds. Total calcium in blood plasma was decreased by 15% (P < 0.05). In
      homogenate and three subcellular fractions (MIII, FI and FIII) of eggshell gland
      mucosa, 45Ca uptake was significantly reduced (i.e. by 29%, 25%, 17% and 35%,
      respectively). A significant reduction (62-66%) was also observed in the
      synthesis of PGF2 alpha, PGE2 and TxB2 by eggshell gland mucosa homogenate. 2.
      The effects of indomethacin treatment on the calcium metabolism of the avian
      eggshell gland are discussed and compared with p,p-DDE-induced alterations in
      calcium metabolism and prostaglandin synthesis by the eggshell gland.

PMID- 1360349
TI  - Binding of tricyclic antidepressant drugs to trophozoites of Giardia lamblia.
AB  - 1. Parameters affecting the binding of the tricyclic drugs imipramine and 3
      chloroimipramine to Giardia lamblia trophozoites were studied. 2. Two to three
      times more chlorimipramine than imipramine was bound, consistent with a similar
      difference in suppressing parasite growth (Weinbach et al., 1985). 3. Kinetic
      analysis and the ease with which bound drugs can be washed out of the parasites
      indicate that noncovalent forces are involved in the drug-parasite interaction.
      4. Evidence is presented that such drugs probably bind to parasite protein at
      common binding sites. 5. The data relate to our earlier observation that
      chlorimipramine is about ten times more effective than metronidazole (Crouch et
      al., 1986) in suppressing G. lamblia growth in vitro. Tricyclic drugs, therefore,
      merit serious consideration as novel therapeutic agents against giardiasis.

PMID- 1360350
TI  - Studies on carbohydrates extracted from native and chemically treated
      Biomphalaria alexandrina snails.
AB  - 1. Carbohydrates were extracted from total tissue extracts of Biomphalaria
      alexandrina snails and were analyzed to their monosaccharides using GLC. 2. The
      snails were chemically treated with thioxanthone derivatives (compounds I, II,
      III) and the change in the monosaccharide constituents of their carbohydrates was
      investigated. 3. The isolated monosaccharides from native and chemically
      pretreated snails were injected into mice and their protective effects were
      examined after infection of mice with cercariae of Schistosoma mansoni. 4. The
      results showed that the main monosaccharides in carbohydrates of snails were
      galactose, glucose, fucose and mannose and that chemical treatment caused a drop
      in the galactose content. 5. Moreover, monosaccharide fractions from snails
      treated with compound III were the most effective in inducing protection against
      Schistosoma infection in mice.

PMID- 1360351
TI  - Regulation of porcine adipose tissue lipolytic activity by adrenergic agonists
      and antagonists.
AB  - 1. Several beta-adrenergic agonists yielded quantitatively and qualitatively
      different lipolytic potencies and efficacies when incubated with porcine adipose
      tissue slices in the presence and absence of theophylline in vitro. Some agonists
      were inactive without theophylline but were active with theophylline. 2. However,
      activity in vitro measured with theophylline was no more closely related to acute
      observations in vivo than activity measured in vitro without theophylline. 3.
      Classification of receptor subtypes or agonists and antagonists as specific for
      receptor subtypes could be totally different in the presence and absence of
      theophylline, depending on the specific agonists or antagonists selected for such
      studies in vitro.

PMID- 1360352
TI  - Cadmium inhibits stimulus-response coupling in skate (Raja erinacea) electric
      organ.
AB  - 1. The effects of cadmium on stimulus-response coupling in the skate (Raja
      erinacea) electric organ were examined. 2. Cadmium decreased the evoked
      electrical discharge and the evoked release of 3H-ACh in a concentration-related
      fashion. 3. Cadmium (100 microM) also blocked voltage-dependent 45Ca uptake. 4.
      Both d-tubocurarine and nifedipine blocked Ca uptake and evoked potential, but
      not 3H-ACh release, thus most of the 45Ca uptake measured was post-synaptic
      through L Ca channels. 5. Nickel, cadmium, and verapamil inhibited 3H-ACh release
      and evoked potential, indicating a block of pre-synaptic T Ca channels.

PMID- 1360353
TI  - Transport of neurotransmitter precursors in a syncytial epithelium.
AB  - 1. Tegumental transport of choline at concentrations ranging from 0.005-5.0 mM
      provided no evidence for saturable, carrier-mediated entry of this amine in the
      tegument of the rat tapeworm (Hymenolepis diminuta). 2. In contrast, the large
      neutral amino acid tryptophan appears to be taken up via a high-affinity
      transporter. In the 1st quartile of 17-day-old tapeworms (Km = 0.033 mM, Vmax =
      0.7 nmol.min-1.g-1), in the 2nd quartile (Km = 0.015 mM, Vmax = 0.3 nmol.min-1.g
      1), in the 3rd quartile (Km = 0.022 mM, Vmax = 0.5 nmol.min-1.g-1) and in the 4th
      quartile (Km = 0.025 mM, Vmax = 0.5 nmol.min-1.g-1) saturable tryptophan
      transport was kinetically characterized. 3. The non-saturable diffusion component
      (Kd) for tryptophan transport ranged from 3.8-10.2 microliters.min-1.g-1. 4.
      These studies suggest choline does not appear to be transported across the
      tapeworm tegument. Saturable transport of tryptophan via a high-affinity carrier
      is reported, and no regional variations in indole amino acid uptake were
      detected.

PMID- 1360354
TI  - Liver microsomal alkoxyphenoxazone O-dealkylases of white Leghorn chickens:
      response to mixed function oxidase inducers.
AB  - 1. The cytochrome P-450 substrates, methoxy-, ethoxy-, pentoxy- and
      benzyloxyphenoxazone were investigated in liver microsomes of phenobarbital- and
      beta-napththoflavone-induced White Leghorn chickens and compared to the rat
      mammalian model. 2. Thirty-two-fold increases in benzyloxyphenoxazone O
      dealkylase and 27-fold increases in ethoxyphenoxazone O-dealkylase activities
      were observed in beta-naphthoflavone-treated chickens compared to only an 18-fold
      increase in ethoxyphenoxazone O-dealkylase activity in beta-naphthoflavone
      treated rats. 3. Decreases in pentoxy- and benzyloxyphenoxazone O-dealkylase
      activities were observed in phenobarbital-treated chickens in contrast to
      increases of 197-fold in pentoxy- and 98-fold in benzyloxyphenoxazone O
      dealkylases in the phenobarbital-treated rats.

PMID- 1360355
TI  - Opposing actions of tolbutamide and glibenclamide on hypoxic pulmonary
      vasoconstriction.
AB  - 1. We show that cromakalin and diazoxide, drugs that activate ATP-sensitive
      potassium (KATP) channels, abolish hypoxic pulmonary vasoconstriction (HPV) of
      isolated, perfused rat lungs. 2. Glibenclamide, an inhibitor of these channels,
      does not affect HPV, but it reverses the relaxation caused by cromakalim and
      diazoxide. 3. Tolbutamide, which has effects similar to glibenclamide in other
      tissues, paradoxically abolishes HPV, an effect reversed by glibenclamide. 4.
      These results suggest that: (i) pulmonary vessels contain KATP channels which are
      normally closed and are not opened by levels of hypoxia that cause constriction,
      (ii) tolbutamide acts on the pulmonary vasculature by a mechanism which differs
      from that of glibenclamide.

PMID- 1360356
TI  - Chromatographic and immunological characterisation of neuropeptide Y-like and
      pancreatic polypeptide-like peptides from the nematode Ascaris suum.
AB  - 1. Immunoreactivity (IR) towards neuropeptide Y (NPY) and pancreatic polypeptide
      (PP) has previously been demonstrated in nematodes by immunocytochemistry (ICC).
      2. The PP- and NPY-IR in the nematode parasite Ascaris suum were analysed using
      HPLC and radioimmunoassays (RIAs) specific for either peptide. 3. Quantitative
      RIA data on the distribution of these IRs in the parasite disagreed with ICC data
      suggesting that different tissue treatments used in the two techniques lead to
      different antigen availability. 4. Significant quantities of PP- and NPY-IR were
      found in the pseudocoelomic fluid suggesting a role for this medium in the
      transport of peptides. 5. The parasite possessed chromatographically-distinct PP-
      and NPY-IRs, with each IR being composed of several distinct molecules.

PMID- 1360357
TI  - Study of the glycogenolytic action of platelet activating factor in Tetrahymena
      pyriformis.
AB  - 1. A novel action of AGEPC on non-inflammatory cells was revealed, namely the
      ability to stimulate glycogenolysis in Tetrahymena pyriformis cells. 2. The
      glycogenolytic effect of AGEPC seems to be dependent on Ca2+ transport and
      regulation, thus the effects are completely inhibited by Verapamil and partially
      by EGTA. 3. The influence of Propranolol, Labetalol, Atenolol and Theophylline in
      the glycogenolytic effect of AGEPC are also studied. 4. Our findings suggest that
      the AGEPC promoted glycogenolysis in Tetrahymena through a mechanism distinct
      from that of catecholamines.

PMID- 1360358
TI  - Actions of APGW-amide and GW-amide on identified central neurons of the snail,
      Helix aspersa.
AB  - 1. Actions of APGWamide and GWamide have been examined on identified central
      neurons of the snail, Helix aspersa. 2. In F1 neurons, both APGWamide and
      GWamide, 0.5-5 microM, reversibly inhibited the amplitude of evoked-IPSPs which
      were dopaminergic, but had no direct effect on membrane potential, cell firing
      rate, or dopamine-induced responses. These results indicate that the actions of
      APGWamide and GWamide in F1 neurons are at presynaptic sites. 3. At
      concentrations between 0.5 and 10 microM, APGWamide and GWamide had direct
      postsynaptic effects on F2 neurons. They inhibited the spike activity and
      hyperpolarized the membrane potential of F2 neurons in a dose-dependent manner
      with a reversal potential around -85 mV which is close to Ek. 4. In K+ free
      solution, the inhibitory effects of APGWamide and GWamide were potentiated, while
      they were reduced by increasing external K+ concentration. Either
      tetraethylammonium (10 mM) or 4-aminopyridine (500 microM) only partially
      prevented the inhibition induced by APGWamide and GWamide on F2 neurons.
      Combination of TEA (5 mM) and 4-AP (250 microM) could abolish this inhibition.
      However, neither 1 mM La2+ nor 10 mM Co2+ could prevent the inhibitory action of
      APGWamide and GWamide. This evidence indicates that the postsynaptic inhibition
      of APGWamide and GWamide on F2 neurons is due to an increase in K+ conductance
      and that both transient K channel (IA) and delay K+ channel (IK) were affected by
      these peptides. 4. APGWamide and GWamide exert both presynaptic and postsynaptic
      effects of Helix neurons, depending on the neuron under study. They are
      qualitatively and quantitatively similar in their presynaptic or postsynaptic
      actions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360359
TI  - In vivo and in vitro effects of beta-endorphin and naloxone on corticosterone and
      cortisol release in male and female water frog, Rana esculenta.
AB  - 1. beta-Endorphin and naloxone effects on corticosterone and cortisol production
      in male and female Rana esculenta, were studied in vivo and in vitro. 2. The in
      vivo and in vitro results were in agreement. 3. beta-Endorphin caused a decrease
      in corticosterone and cortisol release. 4. Naloxone induced an increase in the
      two corticosteroids at the same times as the decrease caused by beta-endorphin.
      5. beta-Endorphin plus naloxone treatment did not change corticosterone and
      cortisol levels. 6. These results suggest that in Rana esculenta opioids are
      involved in the regulation of the hypothalamo-pituitary-interrenal axis; in
      particular, opioids directly modulated interrenal steroidogenesis.

PMID- 1360360
TI  - A comparison of glutathione-dependent enzymes in liver, gills and posterior
      kidney of channel catfish (Ictalurus punctatus).
AB  - 1. Six enzymes which collectively catalyze a number of glutathione-dependent
      synthetic, catabolic and detoxification reactions were examined along with
      glutathione status in liver, gills, and posterior kidney of channel catfish
      (Ictalurus punctatus). 2. Hepatic GSH concentrations were higher than those in
      kidney or gills. Oxidized glutathione (GSSG) concentrations were similar among
      the three tissues. 3. Specific (per unit protein) gamma-glutamylcysteine
      synthetase (GCS) activity was greater in the gills than in liver or posterior
      kidney. However, total organ GCS activity was greatest in the liver. 4. Specific
      and total hepatic glutathione peroxidase (GSH peroxidase) activities were
      substantially greater than those of gills or kidney. 5. Similar specific
      glutathione reductase (GSSG reductase) activities were observed among all three
      tissues. 6. All three tissues exhibited glutathione S-transferase (GST) activity
      towards 1-chloro-2,4-dinitrobenzene (CDNB). Specific and total organ GST
      activities were highest in the liver, followed by the posterior kidney and gills.
      7. Gamma-glutamyltranspeptidase (GGT) activity was present in the posterior
      kidney, but was undetectable in the gills or liver.

PMID- 1360361
TI  - Inhibitory effect of a Microcystis sp (cyanobacteria) toxin on development of
      preimplantation mouse embryos.
AB  - 1. A soluble toxin, purified from the algae bloom of an eutrophic lake dominated
      by Microcystis, is a very effective inhibitor of early embryo development in a
      dose-response relationship. 2. Two- and 8-cell mouse embryos under the influence
      of Microcystis toxin do not reach the developmental stages of morula and
      blastocyst, respectively. 3. Actin cortex is disorganized without change in the
      microtubules structure. 4. Results are discussed in terms of the possible
      mechanisms by which the toxin arrests development considering, specifically,
      effects on the cytoskeleton and/or on voltage-insensitive transmembrane Ca2+
      channels.

PMID- 1360362
TI  - Sensitivities of Achatina giant neurones to putative amino acid
      neurotransmitters.
AB  - 1. GABA receptors in Achatina identifiable giant neurones were classified into
      the muscimol I, muscimol II and baclofen types. Muscimol I and II type GABA
      receptors were sensitive to GABA and muscimol but insensitive to baclofen,
      whereas baclofen type receptors were sensitive to GABA and baclofen but
      insensitive to muscimol. Muscimol I and baclofen types were associated with the
      inhibition caused by GABA, while muscimol II type with the GABA excitation. 2.
      GABA, muscimol and TACA produced a transient outward current (Iout) with an
      increase in membrane conductance (g) of an Achatina neurone, TAN, having the
      muscimol I type GABA receptors. Their relative potency values (RPV) at GABA ED50
      (approximately 10(-4) M) were: GABA:muscimol:TACA = 1:0.6:0.3. The GABA effects
      were potentiated by pentobarbitone, antagonized competitively by pitrazepin and
      non-competitively by picrotoxin and diazepam, and unaffected by bicuculline. The
      ionic mechanism of effects of GABA and its two analogues was the increase in
      membrane Cl- conductance (gCl). 3. GABA and (+/-)-baclofen produced a slow Iout
      with a g increase of another Achatina neurone, RPeNLN, having the baclofen type
      GABA receptors. The two compounds were almost equipotent (ED50: approximately 3 x
      10(-4) M). The ionic mechanism of their effects was the increase in gk. The two
      compounds hardly affected the voltage-gated and slowly inactivating calcium
      current. Iout produced by GABA and (+/-)-baclofen were reduced by TEA, but
      unaffected by 4-AP, bicuculline, pitrazepin and picrotoxin. 4. Beta-hydroxy-L
      glutamic acid (L-BHGA) showed the marked effects on the Achatina giant neurones;
      the two neurones were excited by the compound, whereas the three inhibited. D
      BHGA, L-Glu, D-Glu and NMDA were less effective than L-BHGA or almost
      ineffective. Erythro-L-BHGA was more or less effective than threo-L-BHGA
      according to the neurones tested. 5. alpha-Kainic acid and domoic acid excited
      the two neurones, which were excited by L-BHGA. L-Quisqualic acid showed the
      similar effects to L-BHGA, which were mostly much stronger than L-BHGA. Erythro-L
      tricholomic acid and DL-ibotenic acid showed the effects similar to L-BHGA
      selectively on some neurones. 6. It was pointed out that the pharmacological
      features of GABA on the Achatina neurones are simpler than those of L-BHGA, due
      to the simpler structure of the former compound having less binding sites than
      the latter.

PMID- 1360363
TI  - Effects of ecdysteroids on reproductive physiology of Nippostrongylus
      brasiliensis (Nematoda) in vivo.
AB  - 1. The influence of ecdysteroids (ecdysone and ecdysterone) was investigated on
      the control of reproduction in the parasitic nematode Nippostrongylus
      brasiliensis in vivo. 2. Infestive larvae (L3) were immersed in solutions of
      ecdysteroids (2.2 microM) at 37 degrees C for 4 hr before injection into the
      host. The effect on egg-laying was observed two stages later. 3. The treatment
      increased egg-laying, but had no influence on the timing of the reproductive
      period. The greatest effect was observed with ecdysone, ecdysterone only inducing
      a small and non-significant stimulation under our experimental conditions. 4. The
      physiological role of ecdysteroids in meiosis and gonadal development in
      nematodes is discussed.

PMID- 1360364
TI  - Comparative analysis of inositol phospholipid metabolism in viral and chemical
      transformation of mammalian cells.
AB  - 1. Inositol phospholipid metabolites were measured from virally and chemically
      transformed cells. 2. Increased levels of PIP and PIP2 were observed from both
      transformed cell lines as compared with controls. 3. Intracellular levels of IP3
      were also increased approximately three folds in BPV-1 infected ID 13 cells and
      in 3-MC transformed NIH 3T3 cells. 4. The results suggest that phosphorylation of
      phosphatidylinositols and enhanced generation of IP3 second messenger molecules
      are the common signal transducing process leading to the cell transformation.

PMID- 1360365
TI  - Characterization of cholinesterases from the parasitic nematode Trichinella
      spiralis.
AB  - 1. Trichinella cholinesterases occur in multiple molecular forms which differ in
      size, kinetics, activity with butyrylthiocholine, and effects of inhibitors. 2.
      The 5.3 and 13S forms identified in Trichinella extracts are also found in C.
      elegans and other nematodes but the 7S form which occurs in other nematodes was
      absent from Trichinella detergent extracts. Differences in kinetic and inhibition
      properties among nematode species were also evident. 3. The level of
      cholinesterases in excretory/secretory products is low. 4. Trichinella
      cholinesterases did not elicit a detectable antibody response in mice.

PMID- 1360366
TI  - A metabotropic L-glutamate receptor agonist: pharmacological difference between
      rat central neurones and crayfish neuromuscular junctions.
AB  - 1. 2S,3S,4S-2-(carboxycyclopropyl)glycine (L-CCG-I), a conformationally
      restricted glutamate analogue, is a potent metabotropic L-glutamate receptor
      agonist in the mammalian central nervous system. 2. Depolarizing actions of L-CCG
      I and trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) in the
      newborn rat spinal motoneurone are temperature-sensitive, and are not depressed
      by 3-[(+/-)-2-carboxypiperazin-4-yl] propyl-1-phosphonic acid (CPP) and/or 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX). 3. L-CCG-I and trans-ACPD induced
      oscillatory responses in Xenopus oocytes injected with rat brain mRNA. Oocytes
      with oscillatory responses to L-CCG-I and trans-ACPD showed reversal potential of
      about -20 mV, which was very close to the equilibrium potential of chloride ions.
      4. In rat hippocampal synaptoneurosomes, L-CCG-I stimulated phosphoinositide
      hydrolysis in a concentration dependent manner. L-CCG-I was less potent than
      quisqualate but more potent than trans-ACPD. 5. At low concentrations, L-CCG-I
      did not cause any depolarization of newborn rat spinal motoneurones, but reduced
      substantially amplitudes of monosynaptic reflexes. 6. At the crayfish
      neuromuscular junction L-CCG-I, acting presynaptically, reduced the amplitude of
      excitatory junctional potentials. This action was prevented by application of
      picrotoxin but not pertussis toxin. The actions of trans-ACPD differ from those
      of either L-CCG-I or ibotenate at the crayfish neuromuscular junction. 7. L-CCG-I
      has a potential to provide further useful information on metabotropic L-glutamate
      receptor function.

PMID- 1360367
TI  - Isolation and primary structure of two sulfakinin-like peptides from the
      fleshfly, Neobellieria bullata.
AB  - 1. Two novel insect myotropic peptides termed neosulfakinin-I (Neb-SK-I) and
      neosulfakinin-II (Neb-SK-II) were isolated from the heads of 42 thousand
      fleshflies, Neobellieria bullata (Diptera, Sarcophagidae). 2. A series of four,
      high-performance liquid chromatographic (HPLC), fractionations performed on
      columns with different characteristic features yielded two purified biologically
      active, hindgut motility stimulating fractions, suitable for amino acid sequence
      analysis. 3. The proposed sequences for the two peptides are: Phe-Asp-Asp-Tyr-Gly
      His-Met-Arg-Phe-(NH2), (Neb-SK-I) and X-X-Glu-Glu-Gln-Phe-Asp-Asp-Tyr-Gly-His-Met
      Arg-Phe-(NH2), (Neb-SK-II). 4. These sulfakinins exhibit very high homology to
      putative drosulfakinin sequences which, however, have not yet been isolated, but
      were deduced from a cloned Drosophila gene encoding these peptides. 5. Here we
      provide the first evidence for the expression of such peptides present in
      Dipterans. 6. Insect sulfakinins show structural identities with the hormonally
      active portion of vertebrate gastrin II-, cholecystokinin- and caerulin-related
      peptides and they share common carboxy terminal sequences with
      invertebrate/vertebrate peptides of the FMRFamide peptide family.

PMID- 1360368
TI  - Combined effect of vanadium and zinc on certain selected haematological indices
      in rats.
AB  - 1. Two-month-old Wistar rats of both sexes received, as sole drinking liquid, an
      aqueous solution of ammonium metavanadate (AMV) and zinc chloride (ZC) at
      concentrations of 0.30 mg V/cm3 and 0.12 mg Zn/cm3 respectively, for a period of
      4 weeks. 2. The reference groups received for drinking at this time: water, AMV
      or ZC solutions at the same concentration. 3. In all groups of animals there was
      a statistically significant decrease in the uptake of food, AMV or ZC, as well
      AMV-ZC solutions, as compared with the food and water taken up by the control
      group. 4. In the group of animals receiving AMV or AMV-ZC solution for drinking
      the body weight increment diminished significantly. 5. In the animals drinking
      the AMV-ZC solution a statistically significant decrease in the erythrocyte count
      and haemoglobin level in the peripheral blood were recorded, similar to the
      groups drinking AMV or ZC solution. 6. In rats drinking aqueous AMV or ZC
      solutions and in females receiving AMV-ZC solution the percentage of
      reticulocytes and polychromatophilic erythrocytes increased, moreover, in the
      peripheral blood. It was not, however, associated with marked percentage changes
      in the composition of the bone marrow cells.

PMID- 1360369
TI  - Comparative effects of the polychlorinated biphenyl mixture, Aroclor 1242, on
      porphyrin and xenobiotic metabolism in kidney of Japanese quail and rat.
AB  - 1. Aroclor 1242 (500 mg/kg, p.o.) produced a marked increase in porphyrin content
      of quail kidney (1800-fold), and of rat kidney but to a lesser extent (6-fold).
      2. delta-Aminolevulinic acid synthetase activity was increased 12-fold in quail
      kidney but was unchanged in rat kidney following Aroclor 1242 treatment. 3.
      Uroporphyrinogen decarboxylase activity was significantly inhibited in quail
      kidney but not in rat kidney. 4. Renal ethoxyresorufin O-deethylase activity was
      induced in rat and quail whereas renal ethoxycoumarin O-deethylase and
      glutathione S-transferase activities were induced only in rats by Aroclor 1242.

PMID- 1360370
TI  - Differential effects of 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) on interrenal
      steroidogenesis in male and female rainbow trout Oncorhynchus mykiss.
AB  - 1. The conversion of progesterone to 17 alpha-hydroxyprogesterone (17 alpha-OHP),
      11-deoxycortisol (11-DOCR) and deoxycorticosterone (DOC) was significantly higher
      in female rainbow trout than in male trout; in contrast, the interrenal
      production of cortisol (CR) plus cortisone (CN) was higher in males than in
      females. 2. Following treatment with 1 mg/kg of HCB, the interrenal conversion of
      progesterone to 17 alpha-OHP and 11-DOCR was significantly increased in male and
      female trout but at 20 mg/kg of HCB, the production of these metabolites was
      increased in males and decreased in females; CR+CN production was unchanged after
      HCB treatment in both sexes.

PMID- 1360372
TI  - Biochemical characterization of a variant form of cytosolic epoxide hydrolase
      induced by parental exposure to N-ethyl-N-nitrosourea.
AB  - 1. ENU4 mice express a protein variant originally detected in a CBF1 mouse sired
      by a C57BL/6 mouse exposed to N-ethyl-N-nitrosourea. It appears to be an
      isoelectric point variant of cytosolic epoxide hydrolase. Affinity purified
      cytosolic epoxide hydrolase from ENU4 mice has a pI of approximately 5.1 compared
      to 5.6 in other mouse strains. 2. Clofibrate induced cytosolic epoxide hydrolase
      to similar levels in five strains of mice. However, CBF1 and ENU4 mice were more
      sensitive to the induction of palmitoyl CoA oxidase activity. 3. Except for
      isoelectric point, the physico- and immunochemical properties of cytosolic
      epoxide hydrolase from ENU4 mice were similar to those of the other mouse
      strains. Substrate specificities for five of six substrates tested were also
      similar.

PMID- 1360371
TI  - Evidence for hybrid NMDA/kainate receptors from protein reconstitution studies
      and expression of vertebrate CNS RNAs in Xenopus oocytes.
AB  - 1. A review is presented of recent advances in glutamate receptor research with
      particular emphasis on studies which show that some glutamate receptors in the
      central nervous systems (CNS) of Xenopus and rat contain a mixture of N-methyl-D
      aspartate-sensitive and kainate-sensitive subunits. 2. Protein isolated from
      Xenopus CNS using a domoic acid affinity column exhibits complex pharmacological
      properties. It binds both [3H]kainate and [3H]glycine: the binding of the latter
      is strychnine-insensitive. 3. When reconstituted into lipid bilayers, channels
      gated by kainate and NMDA can be elicited and the properties of these channels
      are similar to those gated by kainate receptors and NMDA receptors, respectively,
      in studies of vertebrate central neurones in situ. 4. The protein can be
      fractionated into two components; one of which is sensitive only to kainate and
      AMPA, the other exhibiting sensitivity to both kainate and NMDA. 5. When RNA
      isolated from Xenopus and rat CNS is injected into Xenopus oocytes, responses to
      kainate and NMDA can be seen within 2-3 days. The responses to co-application of
      these agonists support the contention that some of the glutamate receptors
      expressed in oocytes contain both kainate-sensitive and NMDA-sensitive subunits.

PMID- 1360373
TI  - Esterase heterogeneity in mussel Mytilus galloprovincialis: effects of
      organophosphate and carbamate pesticides in vitro.
AB  - 1. In mussel Mytilus galloprovincialis tissue-specific electrophoretic patterns
      of multiple molecular forms of esterases were observed. 2. Carboxylesterases and
      acetylesterases were identified following the application of pertinent substrates
      and inhibitors. 3. Hepatopancreas was the richest source of esterase activity
      followed by gills, ovaria, adductor muscle and mantle. 4. In vitro studies
      indicated that organophosphate and carbamate insecticides have distinct effects
      on different esterase isozymes. Esterases classified as carboxylesterase were
      more sensitive to parathion and particularly to paraoxon.

PMID- 1360374
TI  - The effect of high fluoride intake on tissue trace elements and histology of
      testicular tubules in the rat.
AB  - 1. Male Wistar rats were exposed to fluoride (F) at concentrations of 100- and
      200 ppm in their drinking water for 6- and 16 weeks. 2. The high F intake caused
      several-fold increase in the F concentrations in the testes and bone as compared
      with control rats, both after the 6- and 16 wk exposure; the bone F, but not
      testicular F, appeared to increase with dose and time. 3. F exposure (100- and
      200 ppm) decreased significantly the concentrations of zinc (Zn) in the testes,
      plasma, liver and kidneys particularly in the 16 wk groups; in the bone Zn tended
      to increase, however. 4. The iron concentrations of the testes and plasma were
      not affected by F, whereas those of the liver, kidneys and bone appeared to
      increase under the influence of F. 5. The concentrations of copper and manganese
      in the testes, liver and kidneys were not changed by F exposure. 6. Fifty percent
      of the 100- and 200 ppm F rats after 16 weeks exhibited histopathologic changes
      in the germinal epithelium of the testes, which resembled those in Zn-deficient
      rats. 7. The data suggest that a deprivation of testicular Zn due to a high F
      intake may be directly responsible for the injury of testicular tubules.

PMID- 1360375
TI  - On metallothionein, cadmium, copper and zinc relationships in the liver and
      kidney of adult rats.
AB  - 1. A short-term exposure of adult Wistar rats to Cu (50 micrograms/ml) and Cd
      (10.0 micrograms/ml drinking water) caused significant changes in the subcellular
      concentrations of Cd, Cu, Zn and metallothionein (MT) in the liver and kidney;
      the concentrations were close to the physiological values, however. 2. To
      establish a relationship between these changes in the subcellular concentrations
      of Cd, Cu, Zn and the level of MT in the post-mitochondrial fraction of the liver
      and kidney, the analytical data (N = 42) were subjected to the multiple
      regression analysis. 3. The analysis showed that MT synthesis in the liver was
      principally induced by small amounts of Cd (0.32-1.4 micrograms/g wet wt) whereas
      in the kidney a level of MT in the post-mitochondrial fraction correlated
      positively with the renal Cd and Cu, as well as with the level of this protein in
      the liver. 4. The above results together with the positive correlation between
      the level of MT in the post-mitochondrial fraction and the concentration of Cu in
      this fraction, as well as the fact that under normal physiological conditions the
      capacity of MT (beta-domain) in the liver and kidney was sufficient to bind 50
      100% of the total post-mitochondrial Cu suggest that MT, first induced by small
      amounts of Cd, may be involved in the metabolism of Cu.

PMID- 1360376
TI  - Alterations induced by fascioliasis and cirrhosis on the biliary excretion of
      cefmetazole in Wistar rats.
AB  - 1. Alterations induced by fascioliasis and cirrhosis on the biliary excretion of
      cefmetazole have been studied in Wistar rats. 2. Both infestation with Fasciola
      hepatica and experimental cirrhosis originated a significant decrease in the
      biliary excretion and in bile flow increase induced by the drug. 3.
      Administration of the beta-lactam antibiotic induced a lower degree of uncoupling
      of biliary lipid secretion in the cirrhotic and fasciolotic animals, but the
      effect was evident in all experimental groups.

PMID- 1360377
TI  - Low magnesium induced epileptiform discharges in neocortical slices (guinea pig):
      increased antiepileptic efficacy of organic calcium antagonist verapamil with
      elevation of extracellular K+ concentration.
AB  - 1. The antiepileptic effect of the organic calcium antagonist verapamil on low
      Mg2+ induced epileptiform discharges in the neocortex was tested. 2. The
      experiments were carried out on slices of the frontal neocortex (guinea pigs).
      Verapamil was tested at normal (4 mmol/l) and elevated (8 mmol/l) KCl levels. 3.
      Verapamil (40, 60 mumol/l) suppressed epileptiform activity in any case. 4. With
      elevated K+ concentration the suppressive effect of verapamil was significantly
      accelerated. 5. Epileptic activity reappeared when verapamil was omitted from the
      Mg(2+)-free superfusate.

PMID- 1360378
TI  - The antifertility agent, gossypol, changes several mitochondrial functions in the
      presence of Mg2+.
AB  - 1. The effect of gossypol in the presence of K+ or Mg2+, or both, was studied on
      ATPase activity and respiration of rat liver mitochondria. 2. Respiration was
      uncoupled in the presence of gossypol, Mg2+, and K+, whereas in the presence of
      gossypol and Mg2+ a partial inhibition was observed. 3. Gossypol stimulated
      ATPase activity in the presence of K+ or Mg2+, but maximal activity was observed
      when both cations were in the incubation medium. 4. Stimulation of ATPase
      activity in the presence of Mg2+ was dose related. 5. EDTA reverted the
      stimulation produced by gossypol on ATPase activity. 6. Gossypol had no effect on
      the ATPase activity of submitochondrial particles, which suggests an indirect
      action of gossypol on the enzyme. 7. Mitochondrial membrane potential showed a
      higher collapse in the presence of gossypol and 1 mM MgCl2. 8. The observed
      effects of gossypol could be explained by the collapse of the mitochondrial
      membrane potential.

PMID- 1360379
TI  - Effects of hydroquinones on intact Trypanosoma cruzi epimastigotes.
AB  - 1. Hydroquinones inhibited the culture growth of Trypanosoma cruzi epimastigotes
      at concentrations lower than 1 mM. 2. Hydroquinones inhibited the oxygen
      consumption on the intact Trypanosoma cruzi cells. I50 values for hydroquinone,
      terbutylhydroquinone and 2,5-di-t-butylhydroquinone were 24.87 mM, 0.88 mM and
      0.26 mM, respectively. t-Butylhydroquinone and 2,5-di-t-butylhydroquinone had a
      Michaelian type kinetic inhibition; hydroquinone also showed a Michaelian type
      kinetic inhibition at low concentrations but at higher concentrations it showed a
      positive cooperativity. 3. These hydroquinones changed the NAD(P) redox-state to
      a more reduced state and that of cytochrome b to a more oxidized state. The
      magnitude of the redox-state change was dependent of the hydrophobicity of the
      derivates. 4. These results suggest that the growth and oxygen uptake inhibition
      by the hydroquinones is due to a blockage of the mitochondrial electron transport
      chain before cytochrome b.

PMID- 1360380
TI  - The allometric approach for interspecies scaling of pharmacokinetic parameters.
AB  - A long standing problem in pharmacokinetics and toxicology is the extrapolation
      and correlation between results obtained in different animal species and man.
      Animal data may be scaled-up to predict PPs in man using the allometric approach.
      The allometric approach is empirical, but easy, and is based on the fact that the
      underlying physiological processes such as blood flow, heartbeat duration, breath
      duration etc. are essentially physical and related to B. This approach is
      generally applicable to compounds that are essentially renally excreted. For
      substances that are highly extracted by the liver, Cltot is a function of the LBF
      among various species. Based on the concept of neoteny, use of brain weight
      affords a more correct approach to the scaling of Cl(int) of low extraction ratio
      drugs. By using the invariant pharmacokinetic time, the superficial differences
      in concentration-time profiles due to chronological time among different species
      are removed. Finally, as Boxenbaum (1984) has said "parameters to be scaled,
      independent variables, and the mathematical relationships used in the scaling
      process are all at the discretion of the investigator. There are no proper or
      improper approaches; the only limitations are those imposed by the investigator."

PMID- 1360381
TI  - Effects of copper and cadmium on growth, superoxide dismutase and catalase
      activities in different yeast strains.
AB  - 1. Three strains of Saccharomyces cerevisiae have been adapted in vitro upon
      treatment with copper or cadmium. Growth rate, cellular size, metal uptake,
      superoxide dismutase and catalase activities were measured. 2. Growth rate and
      metal uptake are quite different among the yeast strains and also for copper and
      cadmium treatment. At the employed concentrations, only cadmium chiefly affects
      the cellular volume. 3. Cu, ZnSOD activity is stimulated in the presence of
      copper, while it is lightly inhibited in the presence of cadmium. Catalase level
      remains almost unchanged in the conditions tested. This lack of correlation is
      then discussed.

PMID- 1360382
TI  - Sphingosine inhibits muscarinic cholinergic receptor binding in rat parotid
      acinar cells.
AB  - 1. Sphingosine inhibited the binding of [3H]quinuclidinyl benzilate (QNB), a
      potent and specific muscarinic antagonist, in dispersed rat parotid acinar cells.
      2. The inhibition of [3H]QNB binding was expressed as decrease in affinity
      without significant change of a number of membrane sites. 3. The effect of
      sphingosine on the binding was not affected by the chelation of extracellular
      Ca2+. 4. H-7, an inhibitor of protein kinase C, failed to decrease [3H]QNB
      binding. 5. Stearylamine, an analogue of sphingosine, was as effective as
      sphingosine in inhibiting [3H]QNB binding. 6. These results suggest that
      sphingosine inhibits muscarinic cholinergic receptor binding by a mechanism that
      is independent on extracellular Ca2+ and protein kinase C.

PMID- 1360383
TI  - Equithesin: a hibernation-inducing drug?
AB  - 1. Hibernating insectivore species (hedgehogs) and non-hibernating rodents
      (guinea pig and rat) were anaesthetized with 'equithesin' (a mixture of chloral
      hydrate, magnesium sulphate, and pentobarbitone sodium). 2. The physiological
      responses shown by the hedgehogs were similar to those observed in hedgehogs
      during a natural or cold-induced hibernation. 3. These responses included a
      strong reduction in body temperature, heart rate, respiration and oxygen
      consumption, and brain activity. 4. Such responses to equithesin were not
      observed in the non-hibernating rodent species. 5. These results suggest that
      equithesin is a potential tool for hibernation research.

PMID- 1360384
TI  - Effects of cholinergic and adrenergic agonists on the secretion of fluid and
      protein by submandibular glands of the hamster and the rat.
AB  - 1. Significant differences were observed between the hamster and the rat in terms
      of the secretion of fluid and protein from submandibular glands in response to
      pilocarpine, phenylephrine and isoproterenol. 2. In both the rat and the hamster
      the secretory responses induced by pilocarpine, phenylephrine and isoproterenol
      were inhibited by pretreatment with 4-DAMP, prazosin and metoprolol,
      respectively. 3. These results suggest that the submandibular glands of the
      hamster and the rat have M3-cholinoreceptors, as well as alpha 1- and beta 1
      adrenoceptors, and that these receptors play different roles in the secretion of
      fluid and protein from hamster and rat submandibular glands.

PMID- 1360385
TI  - Postnatal changes in subcellular distribution of copper, zinc and metallothionein
      in the liver of bank vole (Clethrionomys glareolus): a possible involvement of
      metallothionein and copper in cell proliferation.
AB  - 1. Dramatic interdependent changes in the intracellular concentrations of copper
      (Cu), zinc (Zn) and metallothionein (MT) in the liver of bank voles during the
      first 30 days of their life were observed. 2. The post-mitochondrial Cu, Zn and
      MT (Zn-MT) abruptly decreased between 1 and 3 days following birth but the
      nuclear MT (Cu-MT) and Cu increased at the same time, suggesting that Cu
      displaced Zn already bound to MT in the cytoplasm and subsequently the complex Cu
      MT was translocated to the nuclei. 3. The nuclear Cu concentration reached the
      highest level (62-71% of the total tissue Cu) in the period from day 3 to day 20
      post-partum, just prior to and during a rapidly growing liver. 4. The data
      indicate that MT and Cu may be involved in the hepatocyte proliferation.

PMID- 1360386
TI  - Electrophysiological effects of a neurotoxin extracted from the skin of the
      Australian frog Pseudophryne coriacea.
AB  - 1. The electrophysiological effects of a pumiliotoxin-B-like alkaloid extracted
      from the skin of the Australian frog Pseudophryne coriacea (PsC) have been
      studied in rat superior cervical ganglia at 37 degrees C. 2. PsC (50 mg/ml)
      elicits a broadening of the evoked compound action potential and, at rest, the
      appearance of spontaneous spike discharge at 10-20 Hz. Action potentials
      presumably originate far away from the soma, which is invaded in a typical IS-SD
      sequence. 3. The toxin effect is not related to any direct action on the
      preganglionic fibers of the sympathetic trunk, and does not involve synaptic
      mechanisms. 4. Two-electrode voltage-clamp experiments showed that the main
      properties of the major voltage-dependent ionic currents are apparently
      unaffected by the toxin, while the cell input resistance is considerably reduced.
      5. The data are consistent with the hypothesis that PsC elicits a cationic
      permeability increase generating a pacemaker current in a region close to the
      cell soma.

PMID- 1360387
TI  - Comparative study of the enzymatic, hemorrhagic, procoagulant and anticoagulant
      activities of some animal venoms.
AB  - 1. The enzymatic, hemorrhagic, procoagulant and anticoagulant activities of
      venoms of some animals including snakes, lizards, toads, scorpions, spider,
      wasps, bees and ants were compared. 2. Snake venom was the richest source of
      enzymes among the animal venoms. Most other animal venoms were devoid of
      phosphodiesterase, L-amino acid oxidase, alkaline phosphomonoesterase and
      acetylcholinesterase activities and only a few exhibited arginine ester hydrolase
      activity. These venoms, however, exhibited wide ranges of protease, 5'
      nucleotidase and hyaluronidase activities. Most of the animal venoms examined
      exhibited some phospholipase A activity. 3. Other than snake venoms, only venoms
      of the toad Bufo calamita and the lizards were hemorrhagic, and only venoms of
      the social wasps, social bees and harvester ant exhibited strong anticoagulant
      activity. Procoagulant activity occurs only in snake venoms.

PMID- 1360388
TI  - Effects of amiodarone on triggered activity induced by overdrive stimulation in
      Ca2+ overloaded ventricular muscle from guinea pig.
AB  - 1. The acute effects of amiodarone, a powerful antiarrhythmic drug, on transient
      depolarizations (TDs) and/or triggered activity (TA) induced by an overdrive
      stimulation in the condition of low potassium (2.7 mM) and high calcium (5.4 mM)
      solution were evaluated on isolated ventricular papillary muscles from guinea
      pig, by means of conventional microelectrode techniques. 2. The amplitude of the
      induced TDs was enhanced by increase in stimulus number and frequency during
      overdrive stimulation, and the coupling interval of TDs was shortened. 3.
      Amiodarone (4.4 x 10(-5) M) significantly decreased the amplitude of TDs, and
      prolonged the coupling interval. 4. On the other hand, superfusion with a higher
      concentration (4.4 x 10(-4) M) of amiodarone tended to induce automatic activity.
      5. Possible implications with respect to the antiarrhythmic activity of
      amiodarone are discussed.

PMID- 1360389
TI  - Effects of FMRFamide-related peptides and morphine on the isolated foregut of the
      locust Schistocerca gregaria.
AB  - 1. Morphine and YAGFMamide were the most effective potentiators of 5
      hydroxytryptamine (5-HT)-induced relaxation of the isolated foregut. 2. Morphine
      had no effect on proctolin-induced tissue contraction which was inhibited by
      YGGFMamide and YFMRFamide. 3. The differing potency of FaRPs and morphine to
      potentiate 5-HT effects and reduce proctolin responses suggests that there are
      two separate FaRP receptor sub types. 4. This proposal is supported by the
      observation that, while naloxone (10(-5) M) is a relatively potent antagonist of
      FaRP induced inhibition of proctolin contraction, it has less effect on FaRP
      induced potentiation of 5-HT-induced relaxation.

PMID- 1360390
TI  - The effect of high concentrations of alpha 2-adrenoceptor antagonists on the
      lipolytic responsiveness of isolated human adipocytes.
AB  - 1. Non-specific effects of alpha 2-adrenergic antagonists on human adipocyte
      lipolysis are reported, and revealed that yohimbine and RX-821002 (10(-4) M)
      decreased the maximum lipolytic response and increased the ED50 towards
      norepinephrine and isoproterenol. 2. These effects were not mediated by adenosine
      receptors, alpha 2-adrenoceptors or Gi proteins. 3. Whereas alpha 2-antagonists,
      even as low as 10(-8) M, decreased the binding affinity of [3H]CGP-12177, levels
      as high as 10(-3) M of these antagonists were needed to cause 10-20% displacement
      of the beta-selective antagonist. 4. We propose that the antilipolytic effects of
      alpha 2-antagonists can only partly be explained by non-specific binding to beta
      adrenoceptors, and that some other mechanism is also involved.

PMID- 1360391
TI  - FMRFamide-like immunoreactivity in the stomatogastric nervous system innervating
      the gut of the fly, Sarcophaga bullata.

PMID- 1360392
TI  - The nature of Cl- secretion, induced by carbaryl, across the isolated skin of
      Rana esculenta.
AB  - 1. The pesticide carbaryl induces Cl- secretion through the isolated frog skin.
      2. This effect is due to the activation of both processes responsible for this
      phenomenon: (a) Na+/K+/2Cl- cotransport on the serosal membrane; (b) Cl-
      selective channels on the external membrane. 3. Cl- outflux is inhibited by
      bumetanide (10(-5) M) on the serosal side and by diphenylamine-2-carboxylic acid
      (DPC) (10(-3) M) on the external side. 4. The DPC action is not mimicked by
      Naproxen, a specific inhibitor of cyclooxygenase. 5. A comparison with
      isoprenaline, demonstrates that the carbaryl action is, paradoxically, more
      selective than that of isoprenaline. 6. This selectivity of carbaryl action on Cl
      permeability is confirmed by the fact that, unlike isoprenaline, carbaryl does
      not affect the permeability of Na+ and thiourea.

PMID- 1360393
TI  - Effects of a high molecular weight toxin from the sea anemone Condylactis
      gigantea on cholinergic responses.
AB  - 1. The effects of a high molecular weight toxin isolated from the sea anemone
      Condylactis gigantea (Condytoxina 2) on the cholinergic responses were studied in
      two different preparations: identified cells of a land snail and enzymatically
      dissociated mice sensory neurons. These neurons were studied using intracellular
      recording and concentration clamp techniques respectively. 2. The toxin produces
      a concentration-dependent dual effect on the cholinergic responses in both
      preparations. Thus the application of the toxin at concentrations up to 25 nmol/l
      produces a reversible block of the response whereas higher doses potentiates it.
      3. These results suggest that Condytoxina 2 contains an active compound(s) with
      the capacity to bind to the nicotinic acetylcholine receptor of excitable cells
      in both snail and mice neurons. During this action complex allosteric
      interactions among the binding sites could occur.

PMID- 1360394
TI  - Allergic contact dermatitis due to befunolol in eyedrops.

PMID- 1360395
TI  - Adrenergic stimulation of bovine non-pigmented ciliary epithelial cells raises
      cAMP but has no effect on K+ or Cl- currents.
AB  - Freshly isolated bovine nonpigmented ciliary epithelial cells were studied using
      the whole-cell voltage-clamp and permeabilized patch techniques. In a study of
      148 cells three classes of cell were found; those containing inward currents
      alone, 31%; those containing outward currents alone, 37% and those containing
      both inward and outward currents, 32%. The outward currents exhibited slow,
      delayed activation, were blocked by tetraethylammonium (TEA+) but were not
      effected by changes in [Cai] suggesting they are K(+)-currents similar to IK(V),
      the delayed rectifier. The inward currents were reduced by TEA+ and blocked by
      Cs+ suggesting they are inward rectifier K(+)-currents. Intracellular cAMP levels
      were increased by isoprenaline with a Ka of 20 nM. However, the resting membrane
      potential recorded from whole ciliary processes in intracellular microelectrode
      studies was not effected by adrenergic stimulation, neither were the leak
      current, the outward current nor the sustained inward current significantly
      effected by isoprenaline, noradrenaline or dibutyryl-cAMP in whole-cell and
      permeabilized patch clamp studies.

PMID- 1360397
TI  - The Sixth National Conference on Cor Pulmonale.

PMID- 1360396
TI  - Pharmacological evidence for heterogeneity of ocular alpha 2 adrenoceptors.
AB  - Previous studies have shown that ocular alpha 2 adrenoceptors are located
      prejunctionally on sympathetic neurons and postjunctionally on cells in the
      iris/ciliary body. While the activation of alpha 2 adrenoceptors at each site has
      been postulated to alter aqueous humor dynamics, little is known about the
      pharmacological characteristics of these receptors or their role in the
      modulation of anterior segment function. The purpose of the current study was to
      determine the possible heterogeneity of ocular alpha 2 adrenoceptors using
      relatively selective alpha 2 adrenoceptor agonists and antagonists to examine
      ocular pre- and postjunctional alpha 2 adrenoceptors. Prejunctional alpha 2
      effects were evaluated by means of the cat nictitating membrane (CNM)
      preparation. Postjunctional alpha 2 effects were evaluated by means of the cAMP
      assay in rabbit iris root/ciliary body. In the CNM, the administration of UK-14,
      304 (UK) produced a dose-related inhibition of neuronally mediated contractions.
      Pretreatment with the alpha 2 antagonist rauwolscine caused a 1 to 2 log unit
      right shift in the dose-response curve of UK in the CNM. However, pretreatment
      with alpha 2 antagonist SKF 104078 had no demonstrable effect on UK-induced
      inhibition of neuronally mediated contractions of the CNM. In the rabbit iris
      root/ciliary body, UK produced a concentration-dependent inhibition of cAMP
      accumulation on isoproterenol- and VIP-induced cAMP production. Pretreatment of
      iris root/ciliary bodies with SKF 104078 or rauwolscine reversed the inhibitory
      effect of UK on isoproterenol- and VIP-induced accumulation of cAMP. These data
      provide the first evidence that the pre- and postjunctional alpha 2 adrenoceptors
      represent pharmacologically distinct subpopulations of receptors in the
      eye.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360398
TI  - The effect of exogenous dopamine on ileal smooth muscle of guinea-pigs.
AB  - In the isolated ileum of guinea-pig, treatment with dopamine produced a lowering
      of muscle tone in a dose-dependent manner. Dopamine-induced relaxation at low
      concentration was reversed by haloperidol, the specific antagonist of dopamine
      receptors. The relaxations by dopamine induced at concentration of 1 microM or
      higher were abolished by haloperidol with propranolol. At the concentration
      sufficient to block beta-adrenoceptors, propranolol attenuated this relaxation by
      dopamine at high concentrations. Similar results were also observed in tissues
      concerning the dopamine-stimulated formation of cyclic AMP. Mediation of dopamine
      receptor and beta-adrenoceptor in this cyclic AMP-related relaxation can thus be
      considered. Failure of sulpiride, an antagonist of dopamine DA-2 receptors, to
      reverse the actions of dopamine ruled out the participation of DA-2 receptor.
      Otherwise, SCH23390, the blocker of dopamine DA-1 receptors, reversed the
      responses to dopamine at low concentration only. Actions of dopamine induced at
      high concentration were disappeared in the presence of SCH23390 with propranolol.
      Thus, the obtained data suggest that dopamine induced relaxation of ileal smooth
      muscle through an activation of dopamine DA-1 receptors and/or a stimulation of
      beta-adrenoceptors at the concentrations over 1 microM to result in an increase
      of cyclic AMP in guinea-pigs.

PMID- 1360399
TI  - Evaluation of a method for detection of cells with reduced drug retention in
      solid tumours.
AB  - A method for detection of cells with reduced drug retention was evaluated in
      solid tumours. After a 1 h incubation with daunorubicin (DNR), the right angle
      scatter (RAS), forward angle scatter (FAS), and specific fluorescence (Fluo) were
      measured in sensitive and resistant cells; only Fluo was related qualitatively,
      but not quantitatively, to resistance. Various incubation conditions were
      examined. When the pH of the incubation medium increased, the DNR retention
      increased in sensitive and resistant cells. In contrast, when the cell
      concentration increased, the DNR retention decreased. Using sensitive and
      resistant cell lines, a proportion of resistant cells lower than 10% can be
      detected in a mixture. To analyse cells from solid tumours, the cells were
      dissociated by repeated fine needle aspirations. Tumours from 22 patients have
      been processed with this technique; 8 samples were classified as S (sensitive); 2
      as R (resistant); and 12 as I (intermediate). Further experiments were run to
      study and improve the method. Another method of detection of dead cells was
      tested. The intra-assay variability of the technique was found to be less than
      10%. When the study was performed with different fragments of the same tumour,
      the variation, corresponding to the tumour heterogeneity, rose to 21 to 36%. The
      inter-assay reproducibility was too bad, so a variant of this technique has been
      adapted, using verapamil or cyclosporin A, which is able to block DNR efflux;
      this new method allows tumour cells to be used as their own controls.

PMID- 1360401
TI  - [Co-determination of taurine and other free amino acids in the brain during
      complex immunohistochemical study of the cat and rat somatosensory cortex].

PMID- 1360400
TI  - [Use of bovine serum albumin conjugates with polyalkyleneoxides for studying the
      inhibiting effect of water-insoluble dihydroriboflavin esters].

PMID- 1360402
TI  - The role of the teashirt gene in trunk segmental identity in Drosophila.
AB  - The phenotypes of different mutant combinations of teashirt (tsh) and homeotic
      genes together with their regulatory interactions are described in order to gain
      insight into tsh gene function. We show that when tsh, Scr, Antp and BX-C genes
      are missing, the ventral part of the trunk (or thorax and abdomen) is transformed
      to anterior head identity showing that tsh is a homeotic gene. These genes act
      synergistically to suppress the expression of the procephalic gene labial (lab)
      in subsets of cells in each segment of the trunk. Transcripts from the tsh gene
      always accumulate in segments destined to acquire trunk identities. tsh gene
      activity is required for the normal function of the Antp and BX-C genes, which
      modulate in part the expression of tsh. As a whole, our results suggest that tsh
      plays an essential dual role, during embryogenesis, for determining segmental
      identity of the trunk. First, tsh is required critically for the identity of the
      anterior prothorax. Second, tsh is required globally for segmental identity
      throughout the entire trunk whereas the "classical" homeotic genes have more
      specific roles. Our results are consistent with the idea that tsh is defining the
      ground state of the Drosophila trunk region seen in the absence of the Antp and
      BX-C genes.

PMID- 1360403
TI  - MHox: a mesodermally restricted homeodomain protein that binds an essential site
      in the muscle creatine kinase enhancer.
AB  - Myogenic helix-loop-helix (HLH) proteins, such as myogenin and MyoD, can activate
      muscle-specific transcription when introduced into a variety of nonmuscle cell
      types. Whereas cells of mesodermal origin are especially permissive to the
      actions of these myogenic regulators, many other cell types are refractory to
      myogenic conversion by them. Here we describe a novel homeodomain protein, MHox,
      that binds an A+T-rich element in the muscle creatine kinase (MCK) enhancer that
      is essential for muscle-specific transcription and trans-activation by myogenic
      HLH proteins. MHox is completely restricted to mesodermally derived cell types
      during embryogenesis and to established cell lines of mesodermal origin. In
      contrast to most other homeobox genes, MHox expression is excluded from the
      nervous system, with the highest levels observed in limb bud and visceral arches.
      In adult mice, MHox is expressed at high levels in skeletal muscle, heart and
      uterus. The DNA-binding properties and pattern of MHox expression are unique
      among homeobox genes and suggest a role for MHox as a transcriptional regulator
      that participates in the establishment of diverse mesodermal cell types.

PMID- 1360404
TI  - Relationship between Wnt-1 and En-2 expression domains during early development
      of normal and ectopic met-mesencephalon.
AB  - Grafting a met-mesencephalic portion of neural tube from a 9.5-day mouse embryo
      into the prosencephalon of a 2-day chick embryo results in the induction of chick
      En-2 (ChickEn) expression in cells in contact with the graft (Martinez et al.,
      1991). In this paper we investigate the possibility of Wnt-1 being one of the
      factors involved in En-2 induction. Since Wnt-1 and En-2 expression patterns have
      been described as diverging during development of the met-mesencephalic region,
      we first compared Wnt-1 and En-2 expression in this domain by in situ
      hybridization in mouse embryos after embryonic day 8.5. A ring of Wnt-1
      expressing cells is detected encircling the neural tube in the met-mesencephalic
      region at least until day 12.5. This ring consistently overlapped with the En-2
      expression domain, and corresponds to the position of this latter gene's maximal
      expression. We subsequently studied ChickEn ectopic induction in chick embryos
      grafted with various portions of met-mesencephalon. When the graft originated
      from the level of the Wnt-1-positive ring, ChickEn induction was observed in 71%
      of embryos, and in these cases correlated with Wnt-1 expression in the grafted
      tissue. In contrast, this percentage dropped significantly when the graft was
      taken from more rostral or caudal parts of the mesencephalic vesicle. Taken
      together, these results are compatible with a prolonged role of Wnt-1 in the
      specification and/or development of the met-mesencephalic region, and show that
      Wnt-1 could be directly or indirectly involved in the regulation of En-2
      expression around the Wnt-1-positive ring during this time. We also provide data
      on the position of the Wnt-1-positive ring relative to anatomical boundaries in
      the neural tube, which suggest a more general role for the Wnt-1 protein as a
      positional signal involved in organizing the met-mesencephalic domain.

PMID- 1360405
TI  - Kindled rats are more sensitive than non-kindled rats to the behavioural effects
      of combined treatment with MK-801 and valproate.
AB  - The effects of combined treatment with low doses (0.025-0.05 mg/kg i.p.) of the
      non-competitive NMDA receptor antagonist, MK-801 (dizocilpine), and the
      antiepileptic drug, valproate, were studied in amygdala-kindled and non-kindled
      rats. MK-801, 0.05 mg/kg, did not exert anticonvulsant effects in fully kindled
      rats but increased the anticonvulsant potency of valproate, 100 mg/kg i.p.
      However, the increase in anticonvulsant activity was paralleled by a marked
      increase in adverse effects such as motor impairment and hyperactivity, resulting
      in a considerable reduction of the therapeutic index of the combined treatment
      compared to valproate alone. Furthermore, MK-801 potentiated the adverse effects
      but not the anticonvulsant activity of 50 mg/kg valproate. Combined treatment
      with MK-801 and valproate induced much less marked adverse effects in non-kindled
      rats than in kindled rats. The competitive NMDA receptor antagonist, CGP 37849 1
      mg/kg i.p., did not alter the effects of valproate in kindled rats. The data on
      combined treatment with MK-801 and valproate substantiate the conclusion that
      kindling alters the susceptibility to manipulations of NMDA receptor-mediated
      events.

PMID- 1360406
TI  - Quantitative in vitro and ex vivo autoradiography of the alpha 2-adrenoceptor
      antagonist [3H]atipamezole.
AB  - Atipamezole is an alpha-adrenoceptor antagonist with high affinity and
      selectivity for the alpha 2-receptor. In vitro autoradiography of [3H]atipamezole
      on rat and human brain sections revealed a pattern virtually identical to the one
      observed using 3H-labeled antagonists such as idazoxan or methoxyidazoxan or
      agonists such as p-aminoclonidine and 5-bromo-6-(2-imidazolin-2-yl-amino
      quinoxaline (UK-14304). In vivo studies of [3H]atipamezole demonstrated good
      penetration into the brain (0.3-1.8% injected dose/g at 5 min, depending upon
      brain region). In addition, [3H]atipamezole displayed rapid in vivo clearance of
      nonspecific binding such that at 1 h following an i.v. injection of the drug (100
      microCi/animal, rat tail vein administration) the pattern of radioactivity in the
      brain correlated very well with the receptor distribution as seen by in vitro
      autoradiography. Atipamezole binding in vivo was displaceable by idazoxan. These
      results demonstrate the potential of suitably labeled atipamezole for regional
      studies of brain alpha 2-adrenoceptors in vitro and in vivo, in experimental
      animals as well as in human positron emission tomography (PET) studies.

PMID- 1360407
TI  - Evidence for a noradrenergic component in the antinociceptive effect of the
      analgesic agent tramadol in an animal model of clinical pain, the arthritic rat.
AB  - The analgesic agent tramadol has a potent antinociceptive effect in arthritic
      rats. In the present study, the actions of the selective alpha 2-adrenoceptor
      antagonists yohimbine and idazoxan on this antinociceptive effect were tested in
      arthritic rats, using vocalization thresholds to paw pressure as a nociceptive
      test. The antagonists were administered 30 min before tramadol, at doses (0.5 and
      1 mg/kg i.v.) without action per se, but which prevented the antinociceptive
      action of the prototypic alpha 2-adrenoceptor agonist clonidine (0.1 mg/kg i.v.)
      in these animals. The potent antinociceptive effect of tramadol (1 mg/kg i.v.)
      was significantly decreased (mean total effect reduced about 2-fold) by yohimbine
      and idazoxan. In alpha 2-adrenoceptor antagonists-pretreated arthritic rats, the
      effect of tramadol was almost abolished when tramadol was coinjected with the
      opioid antagonist naloxone. In addition to the involvement of opioid receptors,
      these results provide evidence for a noradrenergic component to the
      antinociceptive action of tramadol in this model of clinical pain.

PMID- 1360408
TI  - [Immunocytochemical studies on the pancreatic endocrine cells in the Japanese
      newt (Cynopus pyrrhogaster)].
AB  - Pancreatic endocrine cells were examined by light and electron microscopic
      immunocytochemistry to discuss the co-localization of peptides in one cell type.
      A cells were irregular in shape with an occasional long cytoplasmic process, and
      contained glucagon-immunoreactive granules with various contours. These granules
      were 160-300nm in diameter with various density, and also immunoreactive to anti
      human pancreatic polypeptide (PP) serum. A part of them were further
      immunoreactive to anti-somatostatin serum. B cells were round to elliptical in
      shape, and often aggregated around the capillaries. Granules of B cells were
      round to irregular in shape, 270-410 nm in diameter, and immunoreactive to anti
      insulin serum. D cells were irregular in shape with meager cytoplasm, and
      contained somatostatin-immunoreactive granules. These granules were ovoid or
      teardrop in shape, 140-250nm in longitudinal diameter, and immunoreactive to both
      anti-somatostatin and anti-human PP sera. PP cells were round to spindle-shaped,
      and contained human PP-immunoreactive round granules 150-35nm in diameter. These
      findings reveal the existence of at least 4 types of endocrine cells secreting
      glucagon, insulin, somatostatin, and PP, respectively, in the newt pancreas, and
      suggest the co-localization of some of these peptides in one cell type.

PMID- 1360409
TI  - Heat-shock responsive elements in the induction of the multidrug resistance gene
      (MDR1).
AB  - The MDR1 gene, considered to be involved in multidrug resistance of cancer cells,
      is expressed in liver, kidney, small intestine and the blood-brain barrier. We
      investigated MDR1 gene expression in the well-differentiated hepatoma cell line
      HepG2 after exposure to several stresses and found that sodium arsenite treatment
      increased MDR1 gene expression 2.6-fold. Deletion analysis of the MDR1 promoter
      indicated that the transcriptional activation after exposure to arsenite depends
      on a 60-bp region containing two heat-shock responsive elements.

PMID- 1360410
TI  - The sequence of human caveolin reveals identity with VIP21, a component of
      transport vesicles.
AB  - Caveolin is a protein present in membrane specializations termed caveolae where
      it may play a structural role. Previous studies on the cDNA sequence of chicken
      caveolin demonstrated that it is an integral membrane protein without significant
      homology to any known protein. The cDNA sequence of human lung caveolin is
      presented here. A striking sequence homology is observed with the chicken
      protein, as well as a very recently reported protein termed VIP21 [(1992) J. Cell
      Biol. 118, 1003-1014], a putative vesicle transport protein isolated from MDCK
      cells. Genomic Southern blots suggest that caveolin is present in a single copy,
      and Northern blots confirm that the caveolin mRNA is elevated in muscle.

PMID- 1360411
TI  - Nitric oxide-releasing compounds inhibit Dictyostelium discoideum aggregation
      without altering cGMP production.
AB  - The effects of nitric oxide-releasing compounds on Dictyostelium discoideum cell
      development and guanylyl cyclase activity were studied. The addition of SNP
      (sodium nitroprusside) or SIN-1 (3-morpholino-syndnonimine) to starved cells
      inhibited their differentiation and aggregation in a concentration-dependent
      manner. In contrast to mammalian systems, SNP did not significantly affect
      guanylyl cyclase activity in cell lysates of D. discoideum, nor did it stimulate
      cGMP production in intact cells. The results suggest that the inhibitory effects
      of NO on D. discoideum cell aggregation are through a mechanism independent of an
      effect on guanylyl cyclase activity.

PMID- 1360413
TI  - [Dental laser welding technique. Procedural report. 1. Quality, expense and risks
      of innovative bonding technique].

PMID- 1360412
TI  - The single-copy gene psbS codes for a phylogenetically intriguing 22 kDa
      polypeptide of photosystem II.
AB  - Recombinant phages that encode the complete precursor polypeptide for the 22 kDa
      polypeptide associated with photosystem II have been serologically selected from
      two lambda gt11 expression libraries made from polyadenylated RNA of spinach
      seedlings. The cDNAs hybridize to a 1.3 kb RNA species. The precursor protein is
      comprised of 274 amino acid residues and carries an N-terminal transit peptide of
      probably 69 amino acid residues. The mature protein exhibits four predicted
      transmembrane segments and is shown to be an integral component of photosystem II
      originating in a single-copy gene. The unique characteristics of this protein
      are: (i) it is the result of a gene-internal duplication of an ancestor with two
      membrane spans, (ii) a striking resemblance to LHC I/II, CP24/CP29 apoproteins,
      and ELIPs, although it does not bind chlorophyll and is present in cyanobacteria,
      and, as these proteins, (iii) it integrates into the membrane with uncleaved
      routing signals that display remarkable resemblance to patterns found in
      bipartite transit peptides.

PMID- 1360414
TI  - [Dental laser welding technique. Procedural report. 2. Indications for use of
      innovative technique].

PMID- 1360415
TI  - [Nitrogen laser vaporization of titanium. Alternative to PVD layering].

PMID- 1360416
TI  - Regulation of rat erythrocyte L-glutamine, L-glutamate and L-lysine uptake by
      short term starvation.
AB  - 1. The kinetic parameters (Km, Vmax and Kd) of L-glutamine, L-glutamate and L
      lysine uptake by isolated red blood cells in fed and 24 hr starved rats have been
      determined. 2. L-Lysine and L-glutamine uptake was best fitted by a two transport
      component: a saturable component and a diffusion one. 3. Starvation brought about
      important decreases in the Km and Vmax for both L-lysine and L-glutamine uptake.
      4. The Kd for L-glutamine showed a significant increase whereas that
      corresponding to L-lysine did not change by starvation. 5. L-Glutamate uptake
      adjusted to diffusion kinetics, with a Kd which did not change due to starvation.
      6. It is concluded that the amino acid uptake showed specific regulation by
      starvation. 7. The mechanism involved is not dependent on protein synthesis-
      given the unnucleated nature of mammal red cells. 8. The magnitude of the changes
      observed in the uptake kinetic parameters may account for the extent of the blood
      amino acid pool changes as those produced in vivo over physiological limits.

PMID- 1360417
TI  - Home deliveries in The Netherlands--perinatal mortality and morbidity.
AB  - The obstetrical organizational system in the Netherlands is based on the
      selection for risk factors. We conclude that: (i) The reporting of perinatal
      death is not complete. (ii) Perinatal mortality can be reduced. (iii) More
      iatrogenic interventions are present in low-risk deliveries in hospitals. (iv)
      Neurological behavior of low-risk babies born at home is equal to those born at
      the hospital, despite the worse maternal profile of the latter and the level of
      acidemia at birth in the first. Good data especially in referred cases are
      necessary before adopting a similar system.

PMID- 1360418
TI  - Longitudinal study of serum thyroid hormone levels during normal pregnancy.
AB  - We undertook a prospective longitudinal study of thyroid function in 60 normal
      pregnant women and measured serum concentrations of T4, triiodothyronine (T3), T
      uptake, thyroxine binding globulin (TBG), free thyroxine index (FTI), free T4,
      albumin and thyrotropin (TSH). From these data we established reference ranges
      for each of these analytes for each trimester and examined the inter
      relationships between laboratory measurements of thyroid function tests. We
      observed significant increases in serum concentrations of thyrotropin and
      decreases in free T4, assays commonly used as first line investigations of
      thyroid activity during pregnancy. However, the 95th centile intervals for both
      analytes remained within the reference range for nonpregnant women.

PMID- 1360419
TI  - Perinatal outcome of very low birthweight infants by mode of delivery.
AB  - In order to evaluate the influence of mode of delivery on perinatal morbidity and
      mortality in vertex infants weighing less than 1500 g (VLBW), we made a
      retrospective study of 152 singleton newborns, in vertex presentation, with a
      birthweight of less than 1500 g, delivered in the Cruces Hospital (Vizcaya,
      Spain), a major perinatal referral center, between 1 January 1987 and 31 December
      1989. Twins and infants with lethal congenital anomalies or gross intrauterine
      growth deviations were excluded from the study (n = 71). Of the infants studied
      (n = 81), 37 were delivered by cesarean section (mean weight 1120 +/- 206 g,
      range: 680-1495 g) and 44 were delivered vaginally (mean weight 1029 +/- 283 g,
      range: 530-1475 g). The patients were divided into four groups: Group A: 500-749
      g (n = 10); Group B: 750-999 g (n = 21); Group C: 1000-1249 g (n = 27); and Group
      D: 1250-1499 g (n = 23). The percentages of cesarean sections in each group were
      10%, 42%, 66% and 39%, respectively. A comparison within each group of immediate
      perinatal outcome (Apgar score and umbilical vein cord pH), as well as mortality
      and sequelae up to 1 year of age did not yield any significant differences
      between cesarean and vaginal birth. We conclude that cesarean delivery does not
      appear to offer improved outcome over vaginal delivery in live births without
      congenital anomalies. For this reason, we believe that fetal weight should not be
      the only obstetrical variable considered when deciding whether or not to perform
      a cesarean section in these circumstances.

PMID- 1360421
TI  - Maternal antihypertensive therapy with beta-blockers associated with poor outcome
      in very-low birthweight infants.
AB  - The progress of 36 very-low birthweight (less than or equal to 1500 g) infants
      born to mothers with pregnancy-induced hypertonia or pre-eclampsia was studied.
      During the first year of life, 7 out of 19 infants died when the mothers'
      antihypertensive regimen included beta-blockers. Four of the deaths occurred
      within 15 days. There were no deaths in 16 infants whose mothers were treated
      with other antihypertensive treatment (P = 0.006). These results suggest that
      maternal beta-blocker therapy may have adverse effects on the very-low
      birthweight infants.

PMID- 1360420
TI  - Interval to delivery in high-risk patients: do tocolytic agents really work?
AB  - Some question whether tocolytic drugs reduce uterine activity and prolong
      gestation. The interval from discontinuance of tocolytics until spontaneous labor
      and delivery in patients (n = 69) with documented preterm labor (PTL) versus
      subjects receiving prophylactic tocolytic therapy (n = 41) was studied. Women
      with documented PTL delivered sooner after cessation of tocolytics (6.1 +/- 6.9
      days) than control (C) patients (14.7 +/- 10.8 days, P less than 0.001). Also, 28
      of the 69 (41%) patients in the PTL group delivered within 24 h of
      discontinuation of tocolysis compared to 4 (10%) in the C group (P less than
      0.0004). We conclude that tocolytic therapy for documented preterm labor
      suppresses uterine activity and when these agents are discontinued, contractions
      return and labor ensues.

PMID- 1360422
TI  - Infraumbilical-ring capillary abdominocentesis in late presentation ectopic
      pregnancy: a prospective study.
AB  - Infraumbilical-ring capillary abdominocentesis was compared with culdocentesis in
      75 cases of suspected ruptured ectopic pregnancy, with patients serving as their
      own controls. There were 43 proven ectopic cases and the diagnosis was known in
      the remaining 32. The accuracy of results was equivalent: P greater than 0.15 for
      false positives and P greater than 0.63 for false negatives. For combined testing
      the positive predictive value reached 97%. The new method was easier to perform
      and should be preferred.

PMID- 1360423
TI  - A comparison of ovulation suppression and ovulation stimulation in the treatment
      of endometriosis-associated infertility.
AB  - This study compares ovulation stimulation or suppression with the pregnancy rate
      among infertile couples with endometriosis. The design is a nonrandomized,
      prospective, multicentered cohort analytic study. Two hundred and ninety-seven
      couples with laparoscopy-proven endometriosis were analyzed: 68 received no
      therapy, 42 received clomiphene and 74 received danazol. Forty patients (22%)
      conceived and pregnancy rates were similar in each treatment group. The relative
      likelihood of pregnancy associated with clomiphene was 2.9 (95% confidence limits
      1.2-7.1); the relative likelihood of pregnancy with danazol was 1.02 (95%
      confidence limits 0.5-2.3). This study suggests that pregnancy rates during
      clomiphene treatment could be superior to expectant therapy, while pregnancy rate
      after danazol is similar to no treatment.

PMID- 1360424
TI  - Endocrinological profile of oligomenorrheic strenuously exercising adolescents.
AB  - The endocrinological profile of 20 strenuously exercising oligomenorrheic
      adolescents divided into 2 groups (groups A and B), was correlated with that of
      10 athletes (group C) with normal menstrual cycles and without strenuous
      exercise. Group A LH serum baseline values were found to be statistically
      significantly lower than those of group C (P less than 0.001). FSH/LH basic
      values were 1.9- and 2.9-times higher in group A athletes than those of group B
      or C (P less than 0.05 and P less than 0.001, respectively). 17 beta-estradiol
      (E2) and prolactin serum levels were found lower in group A and B athletes than
      those of group C (P less than 0.01-0.05). Dehydroepiandrosterone sulfate and
      delta 4 androstenedione serum levels were found lower in group A athletes than
      those of group C (P less than 0.001). The low LH and E2 values indicate the
      anovulatory status of group A and B cases which were also confirmed by
      ultrasound. It is concluded that no severe endocrinological changes exist in
      strenuously exercising oligomenorrheic athletes in relation to menarche.

PMID- 1360425
TI  - Evaluation of regret after tubal sterilization.
AB  - Many different criteria and profiles have been suggested for the possible cause
      of regret and requests for reversal after tubal sterilization. Evaluation of data
      obtained from 2253 women who had undergone tubal sterilization showed a strong
      correlation between regrets and youthful age and to changes in marital situation.
      Previously demonstrated risk factors, such as sterilization in connection with
      abortion or labor were not related to regret in this study material.

PMID- 1360426
TI  - Evaluating the readability of informed consent forms used in contraceptive
      clinical trials.
AB  - The readability level of informed consent forms used in clinical trials on
      contraceptives was determined. Three different formulas for measuring readability
      were used. Some forms received relatively high scores by all three methods. The
      most common problems associated with high readability scores were the use of
      'unfamiliar' words, long words and long sentences. At present all forms used must
      be readable, using the SMOG formula, at a grade 6 level or less.

PMID- 1360428
TI  - Pregnancy in primary liver carcinoma.

PMID- 1360427
TI  - Pregnancy complicated by malaria, precipitate labor and uterine rupture.
AB  - A case of Plasmodium falciparum malaria is reported in a 25-year-old pregnant
      woman with a history of three previous cesarean sections. She developed premature
      precipitate labor which was complicated by stillbirth, uterine rupture, bladder
      and vaginal tears necessitating hysterectomy.

PMID- 1360429
TI  - Supine non-hypotensive syndrome post-epidural analgesia.

PMID- 1360430
TI  - Persistent gestational trophoblastic disease after a diploid partial hydatidiform
      mole coexisting with a normal living fetus.

PMID- 1360431
TI  - Ultrasound imaging in pregnancy. ACOG Committee Opinion: Committee on Obstetrics:
      maternal and fetal medicine. Number 96--August 1991.

PMID- 1360433
TI  - Modulation of HOX2 gene expression following differentiation of neuronal cell
      lines.
AB  - The expression of the genes in the human HOX2 locus has been studied during
      differentiation of two human neuroblastoma (SH-SY5Y and Kelly), a human
      glioblastoma (251-MG), and the murine F9 embryonal carcinoma cell lines. Cells
      were differentiated with retinoic acid (RA), or with RA together with dibutyral
      cyclic AMP (db-cAMP) and nerve growth factor (NGF) in order to assess the changes
      in the expression patterns of these homeobox genes during neuronal
      differentiation. We show that the genes of the HOX2 locus are expressed in a
      complex transcription pattern that varies with cell type. The two uninduced
      neuroblastoma cell lines show a similar pattern of expression for a number of
      HOX2 genes although the levels of expression are different for individual cell
      lines. The embryonal carcinoma cell line F9 expresses low levels of several HOX2
      genes which is restricted to the 5' region of the HOX2 cluster. The glioblastoma
      cell line, 251-MG expresses almost all of the genes of the HOX2 locus.
      Differentiation of these cells modulates the expression of the HOX2 genes in a
      manner that is dependent upon the cell type as well as the differentiation
      factor. Differentiation affects both the level of HOX2 gene expression and the
      distribution of transcript sizes. In conclusion, our analysis reveals a complex
      pattern of expression for the genes of the HOX2 locus in neuronal and glial cells
      and suggests that the cell-specific expression of these genes may be correlated
      with the phenotypic differences that are observed between different neuronal and
      glial cell populations within the nervous system.

PMID- 1360432
TI  - Antibodies to glutamic acid decarboxylase are associated with HLA-DR genotypes in
      both Australians and Asians with type 1 (insulin-dependent) diabetes mellitus.
AB  - Antibodies to glutamic acid decarboxylase, previously known as the 64 kD antigen,
      appear to be more predictive of Type 1 (insulin-dependent) diabetes mellitus in
      Caucasoids than other autoantibodies to islet cell antigens. However,
      seropositivity to glutamic acid decarboxylase is not universal at the onset of
      Type 1 diabetes and the prevalence in Asians is low compared to Caucasoid
      patients. This suggests the involvement of multiple pancreatic autoantigens in
      the Type 1 diabetes autoimmune process or, genetic differences within and between
      ethnic groups that contribute to the heterogeneous autoimmune response to
      glutamic acid decarboxylase or both. Alternatively some cases of Type 1 diabetes
      could have an aetiology unrelated to autoimmunity. This study examined the
      differential response to glutamic acid decarboxylase according to HLA-DR and -DQ
      genotypes, as determined by RFLP, in 49 white Australian and 44 Asian patients
      with Type 1 diabetes. Among Australians heterozygous for HLA-DR3, DR4, 85% were
      positive for antibodies to glutamic acid decarboxylase, significantly different
      (p = 0.039) from the prevalence of 48% in patients with at least one HLA-DR
      antigen other than DR3 or DR4. Also, among Australians, the presence of "low
      risk" HLA-DQ antigens, namely DQw5, DQw6 or DQw7, reduced the prevalence of
      antibodies to glutamic acid decarboxylase by 40% (p = 0.064). Among Asians with
      Type 1 diabetes and with antibodies to glutamic acid decarboxylase, HLA-DR9 was
      significantly (p = 0.037) increased in frequency, at 63% compared with 22% in
      those without glutamic acid decarboxylase antibodies, and the presence of a "low
      risk" HLA-DQ allele reduced the antibody rates by 87% (p = 0.003).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1360434
TI  - Epithelial proliferation in Barrett's esophagus by proliferating cell nuclear
      antigen immunolocalization.
AB  - Proliferating cell nuclear antigen (PCNA) is an auxiliary protein to DNA
      polymerase delta and is an absolute requirement for cellular proliferation.
      Specialized-type Barrett's columnar-lined esophagus (CLE) is associated with
      adenocarcinomatous change. In the present study, the cellular proliferation of
      three histological types of CLE was assessed by semiquantitative evaluation of
      PCNA immunolocalization in 93 biopsy specimens from 45 patients using the murine
      monoclonal PC10. Statistical comparison was performed by the Mann-Whitney U test.
      Luminal surface cell labeling was uncommon in all histological types other than
      specialized CLE where 25 of the 43 biopsy specimens had at least occasional
      luminal surface cell labeling. Mean crypt labeling score of 4.06 for specialized
      type exceeded that for junctional (mean, 3.12; P < 0.001) and fundic types (mean,
      1.6; P < 0.001). Gland cell PCNA staining scores for specialized-type CLE (mean,
      3.18) exceeded that of junctional (mean, 1.97; P < 0.001) and fundic (mean, 1.04;
      P < 0.001). Summated PCNA scores for specialized-type, mean of 8.29, exceeded
      junctional mean score of 5.45 (P < 0.001) and fundic mean score of 2.76 (P <
      0.001). PCNA immunolocalization reveals a high proportion of cells in cycle in
      the specialized-type CLE and expansion of the proliferative compartment, which
      may explain the association of specialized-type CLE with malignancy.

PMID- 1360435
TI  - Effects of somatostatin on renal function in cirrhosis.
AB  - To investigate the renal effects of somatostatin in cirrhosis, renal function and
      plasma and urinary levels of endogenous neurohumoral vasoactive substances were
      measured in conditions of intravenous water overload (20 mL/kg body wt with 5%
      glucose) before and during the intravenous infusion of somatostatin (250-500
      micrograms/h) in 6 cirrhotic patients without ascites and 17 nonazotemic
      cirrhotic patients with ascites. Somatostatin induced a significant reduction of
      renal plasma flow, glomerular filtration rate, and free water clearance in both
      groups of patients. In patients with ascites, somatostatin also reduced urinary
      sodium excretion. Changes in renal function were significantly more marked in
      patients with ascites than in those without ascites and occurred in the absence
      of changes in mean arterial pressure and plasma levels of renin, aldosterone,
      norepinephrine, antidiuretic hormone, and atrial natriuretic peptide.
      Somatostatin induced a significant reduction in the plasma concentration of
      glucagon and urinary excretion of prostaglandin E2 that was not related to
      changes in renal function. These findings indicate that somatostatin
      administration induces renal vasoconstriction and impairs glomerular filtration
      rate, free water clearance, and sodium excretion in cirrhosis by a mechanism
      unrelated to systemic hemodynamics and endogenous neurohumoral vasoactive
      systems.

PMID- 1360436
TI  - Hypersensitivity with hepatotoxicity to mesalazine after hypersensitivity to
      sulfasalazine.
AB  - A 21-year-old woman with Crohn's disease of the colon developed a skin rash after
      3 weeks of treatment with sulfasalazine. Administration of sulfasalazine was
      discontinued. When mesalazine was instituted 1 week later, she developed a severe
      hypersensitivity reaction characterized by fever, diarrhea, skin rash with
      subsequent desquamation, marked atypical lymphocytosis, and severe
      hepatotoxicity. Recovery was complete. The clinical and biological features as
      well as liver pathology of this case bear a striking resemblance to earlier
      reports of hypersensitivity reaction with severe hepatotoxicity to sulfasalazine.
      The authors urge caution when mesalazine is given to a patient with known
      hypersensitivity to sulfasalazine.

PMID- 1360437
TI  - Somatostatin and portal hypertensive bleeding: a safe therapeutic alternative?

PMID- 1360438
TI  - [Overexpression of c-erbB-2 oncogene in primary ovarian cancers: incidence and
      prognostic significance in 243 patients].
AB  - In ovarian cancers, no valuable prognostic factors are available so far for
      predicting biological behaviour and clinical outcome. During the last years,
      overexpression of c-erbB-2-oncogene has been reported to be a prognostic factor
      in various human carcinomas. Its prognostic value in ovarian cancer is still a
      matter of controversy. The records and histological specimens of 243 patients
      with primary ovarian cancer were reviewed. Overexpression of c-erbB-2-oncogene
      encoded transmembrane protein p185 was determined immunohistochemically using
      polyclonal and monoclonal antibodies. Of 243 investigated tumours, 45 (19%) were
      positive. We examined the relationship between p185 and clinical stage,
      histological type, grading and prognosis. p185 overexpression differs within the
      histological subtypes of tumours. No correlation was found between p185
      overexpression and stage or histological grade. The follow-up data demonstrate
      that patients with positive staining for p185 have a significantly worse
      prognosis (p = 0.001) than those with negative staining. These results suggest
      that overexpression of c-erbB-2 oncogene is associated with higher biological
      aggressiveness and unfavourable course of disease.

PMID- 1360439
TI  - Dominant hemimelia and En-1 on mouse chromosome 1 are not allelic.
AB  - Previous studies have shown that En-1, a homeobox-containing gene, maps close to
      or at the Dh locus in the mouse. Since homeobox-containing genes are key genes in
      the control of development the close proximity of En-1 to the developmentally
      significant gene Dh raised the possibility that the Dh mutation represented a
      mutant allele of En-1. A genetic analysis involving En-1, Dh, and other
      chromosome 1 markers (Emv-17, ln and Pep-3) shows that although Dh and En-1 are
      closely linked they are separable by recombination (4/563). The likely gene order
      and recombination frequencies of these loci are: ln (5.2 +/- 0.9) Emv-17 (1.1 +/-
      0.4) Dh (0.7 +/- 0.4) En-1 (3.0 +/- 0.7) Pep-3. This shows that Dh is not a
      mutant allele of En-1.

PMID- 1360440
TI  - Sulphasalazine in ulcerative colitis.

PMID- 1360442
TI  - Signals and Signal Processing in the Immune System, 7th Symposium. Proceedings.
      Koszeg, September 1991.

PMID- 1360443
TI  - Expression of intercellular adhesion molecule-1 (ICAM-1) on human monocytes.

PMID- 1360441
TI  - Malignant change in trichilemmal cysts: a study of cell proliferation and DNA
      content.
AB  - We have examined proliferative activity in a series of pilar and trichilemmal
      cysts using an antibody to proliferating cell nuclear antigen. In benign lesions
      proliferative activity was confined to the basal layers of the squamous
      epithelium. Lesions showing malignant change showed increased proliferative
      activity and were not confined to the basal layer. These findings were correlated
      with studies on DNA content using flow cytometry.

PMID- 1360444
TI  - T cell maturation stage-linked heterogeneity of the glycosylphosphatidylinositol
      membrane anchor of Thy-1.
AB  - We showed that some of Thy-1 molecules on murine thymocytes are resistant to
      phosphatidylinositol-specific phospholipase C (PI-PLC) derived from Bacillus
      thuringiensis. Both immature thymocytes with low CD3 expression and mature thymic
      T lymphocytes with high CD3 expression carried the PI-PLC-resistant Thy-1, and
      the PI-PLC-sensitivity of Thy-1 extensively varied among thymocyte
      subpopulations. In contrast, the same PI-PLC fully hydrolysed the anchor of Thy-1
      on peripheral T lymphocytes. When the latter cells were activated with mitogen in
      vitro, however, some Thy-1 on them became resistant to PI-PLC. We then found that
      virtually all Thy-1 molecules on thymocytes became sensitive to PI-PLC when they
      were treated with hydroxylamine that should cleave ester-linked lipids. The
      result ruled out the possibility that the PI-PLC-resistant Thy-1 had a
      transmembranous peptide sequence, and suggested the presence of an additional
      fatty acyl group on the inositol ring of the Thy-1 anchor. In addition, the
      molecular size of the PI-PLC-resistant membrane-bound Thy-1 was only marginally
      larger than that of the PI-PLC-sensitive solubilized Thy-1 in detergent
      partitioning SDS-PAGE analysis.

PMID- 1360445
TI  - In vivo depletion of interferon-gamma leads to susceptibility of A/J mice to
      mouse hepatitis virus 3 infection.
AB  - The possible role of interferon-gamma (IFN-gamma) in the resistance of A/J mice
      to MHV3 infection was investigated. Monoclonal antibodies specific for IFN-gamma,
      CD4 and CD8 molecules were administered in vivo to deplete selectively the IFN
      gamma synthesized or the appropriate subset of T cells. The animals were then
      infected with MHV3 and the course of infection was followed by studying different
      parameters, such as, the mortality, the virus growth in the tissues and the IFN
      gamma synthesis in sera and peritoneal exudates. After MHV3 infection, a full
      resistance of control A/J mice was observed, in contrast to the high mortality
      rate observed among the depleted animals, where higher virus titers were found in
      different tissues. The IFN-gamma synthesis in sera and peritoneal exudates of
      depleted mice, after MHV3 infection, drastically decreased when compared to that
      detected in control mice. The data presented are consistent with the hypothesis
      that IFN-gamma plays an essential role in the resistance of A/J mice to MHV3
      infection.

PMID- 1360447
TI  - Polyarteritis nodosa (classic form) in a child--a case report.

PMID- 1360446
TI  - Antigenic diversity and variation in blood stages of Plasmodium falciparum.

PMID- 1360448
TI  - Vasodilators inhibit acute alpha 1-adrenergic receptor-induced trophic responses
      in the vasculature.
AB  - Cardiovascular hypertrophy plays an important role in the development and
      maintenance of hypertension. Hyperactivity of the sympathetic nervous system may
      be one of the initiating factors responsible for the stimulation of growth
      processes involved in these structural alterations. We have used a well
      established early biochemical marker of cellular growth processes, induction of
      ornithine decarboxylase (ODC), to determine whether alpha 1-adrenergic receptor
      induced vascular trophic responses are dependent on arterial pressure elevation.
      Hydralazine or felodipine were coadministered to control the alpha 1-adrenergic
      receptor agonist-induced rise in mean arterial pressure (MAP). Methoxamine (2, 5,
      or 10 mg/kg s.c.) increased the average MAP (up to 20 mm Hg) and vascular ODC
      activity (up to ninefold) above control rats over 4 hours. Concomitant
      administration of hydralazine (0.5, 1.25, or 5 mg/kg s.c.) or felodipine (100 or
      250 micrograms/kg s.c.) with methoxamine (10 mg/kg) attenuated the alpha 1
      adrenergic receptor-induced activation of ODC in the aorta and mesenteric
      resistance vasculature, as well as the MAP increases. Vasodilators alone did not
      lower basal vascular ODC activity. The major findings include: 1) alpha 1
      adrenergic receptor activation dose-dependently induces vascular ODC activity
      concomitantly with MAP elevation, 2) vasodilators inhibited both the alpha 1
      adrenergic receptor-induced MAP increases and the activation of mesenteric
      vascular and aortic ODC, and 3) the stimulus-response correlation between MAP
      elevation and mesenteric (r = 0.78) and aortic (r = 0.92) ODC activation was
      characterized by a logistic function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360449
TI  - Regulation of intestinal guanylate cyclase by the heat-stable enterotoxin of
      Escherichia coli (STa) and protein kinase C.
AB  - The heat-stable enterotoxin of Escherichia coli (STa) stimulates membrane-bound
      guanylate cyclase in intestinal epithelium and induces fluid and ion secretion.
      Using the T84 human colon carcinoma cell line as a model, we observed that
      phorbol esters markedly enhanced STa-stimulated cyclic GMP accumulation in T84
      cells (C. S. Weikel, C. L. Spann, C. P. Chambers, J. K. Crane, J. Linden, and E.
      L. Hewlett, Infect. Immun. 58:1402-1407, 1990). In this study we document that
      the phorbol ester treatment increases 125I-STa-binding sites as well as membrane
      bound guanylate cyclase activity in T84 cells and provide evidence that both
      effects are mediated by phosphorylation. Guanylate cyclase activity was increased
      approximately 50% in membranes prepared from intact T84 cells treated with
      phorbol-12,13-dibutyrate (beta-PDB) and after treatment of homogenates with beta
      PDB in a manner dependent on ATP, MgCl2, and cytosol. Similarly, treatment of
      membranes with purified bovine brain protein kinase C in the presence of
      appropriate cofactors and beta-PDB resulted in an increase in STa-stimulated
      guanylate cyclase activity of about 70%. Likewise, the number of 125I-STa-binding
      sites was increased by about 25 to 40% in membranes prepared from intact cells or
      homogenates treated with beta-PDB; no effect on binding affinity (Kd = 0.15 nM)
      was noted. These experiments suggest that protein kinase C may phosphorylate the
      STa receptor-guanylate cyclase or a closely related protein and increase
      guanylate cyclase activity. The stimulatory effects of protein kinase C on STa
      sensitive guanylate cyclase are opposite in direction to the profound inhibitory
      effects of the kinase on atrial natriuretic peptide-stimulated guanylate cyclase,
      demonstrating differential regulation by protein kinases within the guanylate
      cyclase-receptor family.

PMID- 1360451
TI  - Medical treatment of male infertility.

PMID- 1360450
TI  - T-cell-independent stimulation of immunoglobulin secretion in resting human B
      lymphocytes by the mannose-specific adhesin of Escherichia coli type 1 fimbriae.
AB  - Purified Escherichia coli type 1 fimbriae have been shown previously to stimulate
      T-cell-independent proliferation of human B lymphocytes. The response is mediated
      by the mannose-specific, lectin-like adhesin protein FimH. Here we show that type
      1 fimbriae also stimulate immunoglobulin (Ig) secretion by B cells. The response
      was maximal at three days of culture and consisted predominantly of the IgM
      isotype. It was independent of serum components, T lymphocytes, monocytes, and
      natural killer cells. Highly purified resting B cells were induced to proliferate
      and secrete Ig in response to the fimbriae. The role of FimH in the response was
      shown by the failure of FimH- type 1 fimbriae to stimulate and by inhibition of
      the response with alpha-methyl mannoside. In light of the fact that carbohydrate
      binding adhesins have been found on a wide variety of microorganisms, these
      studies suggest the possibility that responses of other cell types to other
      microbial adhesins will be discovered.

PMID- 1360452
TI  - Comparison of different follicle-stimulating hormone and luteinizing hormone
      ratios for ovulation induction during in vitro fertilization.
AB  - Five normally menstruating women were treated in an attempt to induce development
      of multiple follicles. They were randomly divided into two groups. The first
      group, consisting of three women, was treated with a combination of follicle
      stimulating hormone (FSH) and human menopausal gonadotropin (hMG) (combination
      FSH/hMG). The second group, two women, was treated with hMG only. Following a
      nonconceptual cycle, the treatments were exchanged. The increment patterns of
      serum estradiol during the follicular phase and progesterone levels in both
      groups were identical. Ultrasonographic scanning revealed similar number and size
      of the growing follicles, which subsequently terminated in the same oocyte
      recovery rate in both groups (7.6 +/- 3.4 oocytes/procedure in the combination
      FSH/hMG and 8.0 +/- 2.5 in the hMG-only group). Fertilization and cleavage rates
      were also similar. These data indicate that high FSH/LH levels in different
      ratios do not alter ovarian response and oocyte fertilization potential.

PMID- 1360453
TI  - A conservative, low-cost superovulation regimen.
AB  - The protocol reported decreases the cost and inconvenience of inducing the growth
      of multiple ovulatory follicles in selected infertility patients. Safety was
      maintained by treating patients with relatively small amounts of exogenous
      gonadotropins and using patient response to slowly increase gonadotropin
      stimulation in subsequent cycles. The pregnancy rate was 26% per cycle. For
      couples with male factor infertility, it was 20% per cycle. This regimen may be
      especially suitable for the practitioner with only a few patients requiring this
      therapy who may not have the capacity to obtain daily estradiol levels.

PMID- 1360454
TI  - Life styles of men in barren couples and their relationship to sperm quality.
AB  - This study is based on a questionnaire which focused on the possible association
      between life-style factors and male fertility in a group of 252 men attending our
      laboratory in connection with a fertility investigation. Their answers were
      correlated to sperm quality. No association could be documented between sperm
      quality and smoking habits, coffee drinking, a moderate alcohol intake, exposure
      to heat (sauna, hot baths, type of underwear, sedentary activities), or physical
      activities in their leisure time. In contrast, the reported average ejaculation
      frequency was significantly positively correlated to the motility of the sperm (%
      progressive), and inversely related to the proportion of sperm with abnormal
      morphology and semen volume. This indicates that the life style of the subject
      has little if any impact on semen quality, at least within the limits recorded in
      the present study.

PMID- 1360456
TI  - Should androgen levels be measured in hirsute women with normal menstrual cycles?
AB  - In a study of 129 consecutively referred hirsute women, 40% had regular menstrual
      cycles. About one half of such individuals had elevated levels of one or more
      androgens (DHEAS, testosterone or free testosterone index), whereas a higher
      proportion (69%) of hirsute women with oligo-amenorrhea were abnormal. Mean
      androgen levels in regularly cycling hirsute women were higher than in controls,
      but lower than or equal to those in oligo-amenorrheic hirsutism. Thus, menstrual
      status does not predict androgen status in hirsute women.

PMID- 1360455
TI  - Late luteal phase progestogen-dependent endometrial protein levels in women with
      in-phase biopsies--can low levels predict a subfertile group?
AB  - A group of infertile women who had luteal phase defects (LPD), but in whom
      follicular maturation was deemed normal, were treated with progesterone until the
      endometrial biopsy was corrected. At the time the corrected biopsy was obtained,
      serum was taken and the progestogen-dependent endometrial protein (PEP)
      concentration was determined. Serum PEP concentration in patients who
      successfully conceived was 102.5 +/- 62.6% units/mL, while PEP concentrations in
      patients who failed to conceive were 57.9 +/- 34.4% (P = .003). In patients whose
      PEP value was more than two standard deviations below the corresponding mean
      control PEP, pregnancy was achieved in 6/17 (35.3%). The conception rate was
      significantly greater (25/35, 71.4%) in patients with values higher than this.
      Thus, the PEP concentration in serum may identify a group of patients with
      persistent LPD despite apparent normalization of the morphology of late secretory
      phase endometrium, which might explain some cases of cryptic, unexplained
      infertility.

PMID- 1360457
TI  - Effect of boar seminal plasma immunosuppressive factor on NK cell activity and
      skin graft survival.
AB  - The B 10 strain of mice was used to test the effect of the boar seminal vesicle
      immunosuppressive factor on the female mouse response to the male-specific
      transplantation antigen. Influence of this factor on human natural killer (NK)
      cell activity was also studied. No inhibitory effect of the immunosuppressive
      factor on graft survival was apparent during a time of more than 200 days, nor
      did the factor suppress NK cell activity.

PMID- 1360459
TI  - Comparative effects of different methods of anastomosis on rat uterine horn.
AB  - This study compares the results of microsurgical uterine horn anastomosis
      performed using fibrin glue (FK-1), 8/0 Prolene sutures, or fibrin glue in
      combination with 8/0 Prolene sutures. Thirty-two rats were divided into three
      groups. Three results were studied: frequency of adhesion formation in the area
      of anastomosis, uterine horn patency, and pregnancy rates. Compared with
      microsurgical sutures, fibrin glue used for the anastomosis of uterine horns in
      rats results in identical pregnancy and patency rates. Moreover, the formation of
      adhesions was significantly lower and the duration of surgery was shortened.

PMID- 1360458
TI  - Ultrastructural comparison of human spermatozoa along a Percoll density gradient.
AB  - We studied the possible deleterious effects of Percoll gradient centrifugation
      processing on spermatozoal integrity in 18 semen samples from patients
      participating in our IVF program, using optical and electron microscopy.
      Substantial recovery by sperm count was obtained in the 100% Percoll layer (32%),
      with greater numbers of motile, alive spermatozoa (P < .01). Whether samples
      studied were from fertile or infertile men, no significant differences, using
      nonparametric tests with transmission electron microscopy, appeared in
      spermatozoal membranes, acrosomes, or nuclei either before or after Percoll
      treatment. No deleterious effects of Percoll use on spermatozoa were detected
      during the study.

PMID- 1360461
TI  - Family planning and contraception: options for the 1990s--introduction.

PMID- 1360460
TI  - Predictive value of sperm hyperactivation measurements based on the dilution
      effect method in clinical in vitro fertilization.
AB  - Sperm hyperactivation motility characterized by wide oscillatory movements of the
      sperm head, nonlinear directions, and rapid motility with occasional star-shaped
      pattern of movement was measured during routine semen analyses prior to an in
      vitro fertilization procedure. The method consisted of diluting liquefied semen
      1:20 with Ham's F-10 supplemented with processed human cord sera followed by
      incubation at 37 degrees C for 30 minutes. At the end of the incubation period,
      aliquots of semen samples were evaluated by phase contrast microscopy for sperm
      hyperactivation. The results indicated that (1) sperm samples exhibiting 15% or
      more hyperactive motility were associated with a significantly higher percent
      fertilization of oocytes during the IVF procedure; (2) sperm hyperactive motility
      was correlated to sperm fertilizability during IVF treatment cycles.

PMID- 1360462
TI  - Benefits and risks of birth control in U.S. women.

PMID- 1360464
TI  - Ovarian consequences of the transient interruption of combined oral
      contraceptives.
AB  - The combined oral contraceptive pill is an efficient means of contraception. It
      acts at different levels of the genital tract. Despite its efficiency, it is
      universally suggested that patients take the pill at regular daily intervals.
      Little attention has been given to the question of what happens if you miss the
      pill one day or more. A study was undertaken to evaluate the consequences of pill
      misses at different times of the cycle. Forty-seven young, healthy, normally
      menstruating patients voluntarily enrolled. All were given Cilest (ethinyl
      estradiol 35 micrograms and norgestimate 250 mg, Cilag France) for 21 days
      without any misses. Then, after a 7-day interval, they were prescribed one (group
      1), two (group 2), three (group 3) or four days of pill misses, to occur
      respectively on day 1 (group a), 6 (group b), 12 (group c) or 18 (group d) of a
      new 21 day cycle; supplementary contraceptive means were recommended. Four
      patients had no miss prescribed and served as controls. Ovarian function was
      evaluated with daily estrogen measurements (E1 + E2 enzymatic dosage, BioMerieux,
      France) and ultrasound examinations. When required, because of significant
      increase in estrogen or because of follicular growth detected on ultrasound, LH
      and progesterone were measured. None of the patients experienced a normal
      ovulation. Four patients (1 control, 1 from group 2a, and 2 from group 3a) had a
      significant increase in estrogen levels and had a follicular image on
      ultrasounds. One of them (group 3a) had a follicular rupture, but none had a LH
      surge or increase in progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360463
TI  - Cilest (norgestimate/EE): some clinical observations.

PMID- 1360465
TI  - A postpartum clinical trial with a new progestin, norgestimate.

PMID- 1360466
TI  - An alternative to oral contraception--the IUD.

PMID- 1360467
TI  - New insights into the development of neural crest derivatives.

PMID- 1360469
TI  - U.S.-Japan seminar on "genomic instability during carcinogenesis and tumor
      progression".

PMID- 1360468
TI  - Spermidine/spermine N1-acetyltransferase, a new biochemical marker for epithelial
      proliferation in rat bladder.
AB  - We examined the activity of spermidine/spermine N1-acetyltransferase (SAT), a
      rate-limiting enzyme of the biodegradation of polyamines, in N-butyl-N-(4
      hydroxybutyl)nitrosamine-induced transitional cell carcinoma (TCC) and melamine
      induced papillomatosis of rat bladder, and compared the activity to that of
      ornithine decarboxylase (ODC). Both activities were higher in both lesions than
      in control rats. The difference between SAT and ODC activities in cancerous
      tissue and papillomatosis was not significant. Cells stained for proliferating
      cell nuclear antigen (PCNA) were abundant in papillomatosis. TCC had areas with
      much PCNA. The results indicated that an elevation of SAT activity occurs in both
      reversible and irreversible proliferation of bladder epithelium and could be
      important in bladder carcinogenesis.

PMID- 1360470
TI  - Therapy of Parkinson's disease: are we at the end of the road?

PMID- 1360471
TI  - Hypopituitarism following snake bite.

PMID- 1360472
TI  - A man with persistent fever and diffuse abdominal pain.

PMID- 1360473
TI  - Determination of diphenylmethane antihistaminic drugs and their analogues in body
      fluids by gas chromatography with surface ionization detection.
AB  - Eleven diphenylmethane antihistaminic drugs and their analogues were tested for
      their detection by capillary gas chromatography (GC) with surface ionization
      detection (SID). The GC-SID response was highest for doxylamine, diphenhydramine
      and orphenadrine and lowest for terodiline, clemastine and pipethanate. The
      detection limits for drugs with the highest response were 2-5 pg (ca. 6-20 fmol)
      on-column (100-250 pg/ml of body fluid). The detection limits with GC-SID were 10
      100 times higher than those with GC with nitrogen-phosphorus detection. A
      detailed procedure for the isolation of the antihistaminics from human whole
      blood and urine by the use of Sep-Pak C18 cartridges, prior to GC-SID, is also
      presented. The recoveries of the drugs (50 or 500 pmol), which had been added to
      1 ml of body fluids, were > 60%. The baselines remained steady as the column
      temperature was increased and the background was clean, especially for whole
      blood extracts.

PMID- 1360474
TI  - Influence of transcutaneous electrical nerve stimulation on memory in patients
      with dementia of the Alzheimer type.
AB  - This study examined the effect of transcutaneous electrical nerve stimulation
      (TENS) on memory in patients with dementia of the Alzheimer type. It was
      hypothesized that, in the early stage of the illness, electrical stimulation
      could activate the affected cortical regions by stimulating the neurotransmitter
      systems projecting to these areas. The results reveal that electrical stimulation
      improves the verbal long-term memory in these patients. Moreover, verbal fluency
      improves more in patients who received electrical stimulation than in patients
      who received control treatment. However, electrical stimulation does not
      influence the visual long-term memory of the patients, nor does it affect their
      verbal and nonverbal short-term memory. Underlying theoretical mechanisms are
      discussed.

PMID- 1360475
TI  - Use of randomly amplified polymorphic DNA markers to distinguish isolates of
      Aspergillus fumigatus.
AB  - Forty-four oligonucleotide decamers were tested for their abilities to generate
      randomly amplified polymorphic DNA (RAPD) markers from genomic DNAs of three
      different isolates of Aspergillus fumigatus. Seven primers generated RAPDs that
      allowed the three isolates to be differentiated; one of the primers also yielded
      a unique RAPD pattern in each of an additional six fungal isolates, demonstrating
      the utility of this technique for distinguishing between A. fumigatus isolates.

PMID- 1360476
TI  - Epidemiology of nosocomial acquisition of Candida lusitaniae.
AB  - Candida species are important nosocomial pathogens; however, little is known
      about the epidemiology of Candida lusitaniae, an organism frequently resistant to
      amphotericin B. We evaluated 98 patients admitted to the bone marrow transplant
      and medical intensive care units of a tertiary-care hospital. Each patient with
      C. lusitaniae was matched with control patients. Restriction fragment analysis of
      DNA was used to determine strain relatedness. Seven patients (7.1%) with C.
      lusitaniae were identified; five acquired C. lusitaniae after admission to the
      study unit. All isolates were susceptible to amphotericin B. There were no
      differences between patients and controls with regard to duration of stay in the
      study unit, antibiotic administration, antifungal therapy, immunosuppressive
      therapy, catheter use, or underlying disease. Temporal and geographic clustering
      of five patients with identical strains occurred. No common source was
      identified. Restriction fragment analysis revealed a total of eight strains, and
      five patients shared one strain type. These results demonstrate exogenous
      acquisition of C. lusitaniae. The mechanism of acquisition is probably indirect
      contact transmission between patients.

PMID- 1360477
TI  - Mycobacteria in Crohn's disease: DNA probes identify the wood pigeon strain of
      Mycobacterium avium and Mycobacterium paratuberculosis from human tissue.
AB  - Mycobacterium paratuberculosis is known to cause Johne's disease, a granulomatous
      ileitis in ruminants, and may be involved in some cases of Crohn's disease. Like
      M. paratuberculosis, the wood pigeon strain of Mycobacterium avium may also show
      mycobactin dependence on primary isolation that is attenuated on further
      subculturing. A wood pigeon strain, M. avium restriction fragment length
      polymorphism (RFLP) type A/I, is also capable of causing granulomatous ileitis in
      experimental animal models but is not known to cause disease in humans. M. avium
      RFLP type A is associated with disease in immunocompromised hosts. Three DNA
      probes, pMB22 and the two subclones pMB22/S4 and pMB/S12, were found to be
      capable of distinguishing among M. paratuberculosis, M. avium type A, and M.
      avium type A/I (wood pigeon strain) on the basis of RFLPs. These DNA probes were
      used to identify two mycobacterial isolates (M. paratuberculosis and M. avium
      type A/I, wood pigeon strain) derived from the intestinal tissues of two patients
      with Crohn's disease. In addition, the wood pigeon strain of M. avium was
      identified from a patient with ulcerative colitis, and M. avium RFLP type A was
      identified from a patient with colonic carcinoma. This is the first time that M.
      avium A/I (wood pigeon strain) is known to have been isolated from human tissue.
      There are too few isolates to speculate about the etiological significance of
      mycobacteria and inflammatory bowel disease, but it is reasonable to conjecture
      that M. paratuberculosis may be responsible for some cases of Crohn's disease and
      that the wood pigeon strain of M. avium may also be an inflammatory bowel disease
      pathogen in humans.

PMID- 1360478
TI  - Detection of mRNA by in situ hybridisation and in northern blot analysis using
      oligodeoxynucleotide probes labelled with alkaline phosphatase.
AB  - AIMS: To assess whether a reduction in intensity of signal observed using an
      alkaline phosphatase labelled oligodeoxynucleotide probe could be explained on
      the basis of procedural steps rather than reduced sensitivity. METHOD: Signal
      intensity was assessed on in situ hybridisation for pro-opiomelanocortin (POMC)
      mRNA in rat pituitary and for somatostatin mRNA in human pancreas and in northern
      blot analysis for POMC mRNA in the presence and absence of formamide. The direct
      effects of formamide on the alkaline phosphatase detection step were assessed
      using histochemical enzyme detection in rat kidney. RESULTS: All signals were
      reduced in systems containing formamide. CONCLUSIONS: In the absence of formamide
      clear, strong signals for specific mRNAs can be obtained by in situ hybridisation
      and northern blot analysis using oligodeoxynucleotide probes directly labelled
      with alkaline phosphatase. Formamide seems to inhibit the activity of alkaline
      phosphatase.

PMID- 1360479
TI  - Directional atherectomy for treatment of restenosis within coronary stents:
      clinical, angiographic and histologic results.
AB  - OBJECTIVES: The safety and long-term results of directional coronary atherectomy
      in stented coronary arteries were determined. In addition, tissue studies were
      performed to characterize the development of restenosis. METHODS: Directional
      coronary atherectomy was performed in restenosed stents in nine patients (10
      procedures) 82 to 1,179 days after stenting. The tissue was assessed for
      histologic features of restenosis, smooth muscle cell phenotype, markers of cell
      proliferation and cell density. A control (no stenting) group consisted of 13
      patients treated with directional coronary atherectomy for restenosis 14 to 597
      days after coronary angioplasty, directional coronary atherectomy or laser
      intervention. RESULTS: Directional coronary atherectomy procedures within the
      stent were technically successful with results similar to those of the initial
      stenting procedure (2.31 +/- 0.38 vs. 2.44 +/- 0.35 mm). Of five patients with
      angiographic follow-up, three had restenosis requiring reintervention (surgery in
      two and repeat atherectomy followed by laser angioplasty in one). Intimal
      hyperplasia was identified in 80% of specimens after stenting and in 77% after
      coronary angioplasty or atherectomy. In three patients with stenting, 70% to 76%
      of the intimal cells showed morphologic features of a contractile phenotype by
      electron microscopy 47 to 185 days after coronary intervention. Evidence of
      ongoing proliferation (proliferating cell nuclear antigen antibody studies) was
      absent in all specimens studied. Although wide individual variability was present
      in the maximal cell density of the intimal hyperplasia, there was a trend toward
      a reduction in cell density over time. CONCLUSIONS: Although atherectomy is
      feasible for the treatment of restenosis in stented coronary arteries and initial
      results are excellent, recurrence of restenosis is common. Intimal hyperplasia is
      a nonspecific response to injury regardless of the device used and accounts for
      about 80% of cases of restenosis. Smooth muscle cell proliferation and phenotypic
      modulation toward a contractile phenotype are early events and largely completed
      by the time of clinical presentation of restenosis. Restenotic lesions may be
      predominantly cellular, matrix or a combination at a particular time after a
      coronary procedure.

PMID- 1360480
TI  - Silymarin protects against paracetamol-induced lipid peroxidation and liver
      damage.
AB  - The effect of silymarin on liver damage induced by acetaminophen (APAP)
      intoxication was studied. Wistar male rats pretreated (72 h) with 3
      methylcholanthrene (3-MC) (20 mg kg-1 body wt. i.p.) were divided into three
      groups: animals in group 1 were treated with acetaminophen (APAP) (500 mg kg-1
      body wt. p.o.), group 2 consisted of animals that received APAP plus silymarin
      (200 mg kg-1 body wt. p.o.) 24 h before APAP, and rats in group 3 (control)
      received the equivalent amount of the vehicles. Animals were sacrificed at
      different times after APAP administration. Reduced glutathione (GSH), lipid
      peroxidation and glycogen were measured in liver and alkaline phosphatase (AP),
      gamma-glutamyl transpeptidase (GGTP) and glutamic pyruvic transaminase (GPT)
      activities were measured in serum. After APAP intoxication, GSH and glycogen
      decreased very fast (1 h) and remained low for 6 h. Lipid peroxidation increased
      three times over the control 4 and 6 h after APAP treatment. Enzyme activities
      increased 18 h after intoxication. In the group receiving APAP plus silymarin,
      levels of lipid peroxidation and serum enzyme activities remained within the
      control values at any time studied. The fall in GSH was not prevented by
      silymarin, but glycogen was restored at 18 h. It was concluded that silymarin can
      protect against APAP intoxication through its antioxidant properties, possibly
      acting as a free-radical scavenger.

PMID- 1360482
TI  - A new fluorescence method for alkaline phosphatase histochemistry.
AB  - We have developed a new fluorescence method for the histochemical localization of
      alkaline phosphatase activity. Calcium phosphate deposited at the sites of
      alkaline phosphatase activity in a Gomori-type reaction are identified by calcium
      binding fluorochromes. The calcium binding fluorochromes calcein, calcein blue,
      and xylenol orange were investigated, with each fluorochrome being included in
      the alkaline phosphatase incubating medium and used in a single-step procedure.
      Alkaline phosphatase activity was studied in freeze-substituted, resin-embedded
      human liver and jejunal biopsies, and each fluorochrome produced intense
      fluorescence of different colors at sites of alkaline phosphatase activity.
      Calcein, calcein blue, and xylenol orange produced green, blue, and red
      fluorescence, respectively. Sites of enzyme activity were accurately localized
      without evidence of diffusion, and there was an absence of non-enzyme-catalyzed
      binding of any of the fluorochromes to tissue. This fluorescence method, which is
      particularly suited to investigating the localization and distribution of the
      activity of different enzymes in the same section, was used to investigate the
      distribution and co-localization of alkaline phosphatase and aminopeptidase M in
      human liver and jejunum.

PMID- 1360481
TI  - Investigation of peroxisomal lipid beta-oxidation enzymes in guinea pig liver
      peroxisomes by immunoblotting and immunocytochemistry.
AB  - We investigated the immunoreactivity of the peroxisomal lipid beta-oxidation
      enzymes acyl-CoA oxidase, trifunctional protein, and thiolase in guinea pig liver
      and compared it with that of homologous proteins in rat, using immunoblotting of
      highly purified peroxisomal fractions and monospecific antibodies to rat
      proteins. In addition, the immunocytochemical localization of beta-oxidation
      enzymes in guinea pig liver was compared with that of catalase. All antibodies
      showed crossreactivity between the two species, indicating that these peroxisomal
      proteins have been well conserved, although all exhibited some differences with
      respect to molecular size and, in the case of acyl-CoA oxidase, in frequency of
      the immunoreactive bands. In the latter case, a distinct second band in the 70 KD
      range was observed in guinea pig, in addition to the regular band due to subunit
      A present in rat liver. This novel band could be due either to
      trihydroxycoprostanoyl-CoA oxidase or to the non-inducible branched chain fatty
      acid oxidase described recently. All three beta-oxidation enzymes were
      immunolocalized by light and electron microscopy to the matrix of peroxisomes, in
      contrast to catalase, which is also found in the cytoplasm and the nucleus of
      hepatocytes in guinea pig liver.

PMID- 1360484
TI  - [Molecular biological approach to neuromuscular diseases].

PMID- 1360483
TI  - The use of unfixed cryostat sections for electron microscopic study of D-amino
      acid oxidase activity in rat liver.
AB  - Unfixed cryostat sections of rat liver were incubated to demonstrate D-amino acid
      oxidase activity at the ultrastructural level. Incubation was performed by
      mounting the sections on a semipermeable membrane which was stretched over a
      gelled incubation medium containing D-proline as substrate and cerium ions as
      capture reagent for hydrogen peroxide. After an incubation period of 30 min,
      ultrastructural morphology was retained to such an extent that the final reaction
      product could be localized in peroxisomes, whereas the crystalline core remained
      unstained. Control incubations were performed in the absence of substrate; the
      lack of final reaction product in peroxisomes indicated the specificity of the
      reaction. We conclude that the semipermeable membrane technique opens new
      perspectives for localization of enzyme activities at the ultrastructural level
      without prior tissue fixation, thus enabling localization of the activity of
      soluble and/or labile enzymes.

PMID- 1360485
TI  - [Metabolic disease and molecular biology].

PMID- 1360487
TI  - [Clinical study on pulmonary hypertension].

PMID- 1360486
TI  - [Clinical study on Crohn disease].

PMID- 1360488
TI  - [Prevention of drug hypersensitivity].

PMID- 1360489
TI  - Reduction of cardiovascular side effects associated with ocular administration of
      metipranolol by inclusion in polymeric nanocapsules.
AB  - A new formulation of metipranolol base for ophthalmic administration was
      developed consisting of a colloidal suspension of polyepsiloncaprolactone
      nanocapsules with an oily core (Migliol 840) in which the drug is dissolved.
      Physicochemical properties of the nanocapsules show that the polymer coating
      around the oily droplets causes an important reduction of the droplet size, with
      no significant modification of the surface charge noted. When this formulation
      was administered to rabbits, a reduction of intraocular pressure similar to that
      seen with commercial eye drops was observed. Nevertheless, the evaluation of the
      cardiovascular side effects clearly showed lower conjunctival absorption of the
      encapsulated drug compared with the commercial drops. The direct (bradycardia)
      and the indirect evaluation (based on the study of the influence on the
      hypotensive and positive chronotropic effects of isoprenaline) showed that
      blockage of beta-adrenoreceptors was reduced greatly by the topical
      administration of the new formulation.

PMID- 1360490
TI  - The treatment of depression: prescribing practices of primary care physicians and
      psychiatrists.
AB  - BACKGROUND: Depression is one of the most common mental disorders treated by
      primary care physicians. Concern has been expressed that primary care physicians
      underutilize antidepressants and overutilize anxiolytics in their management of
      depressive disorders. METHODS: Data from the 1980, 1985, and 1989 National
      Ambulatory Medical Care Surveys were used to examine the pharmacologic treatment
      provided by primary care physicians and psychiatrists during office visits with
      patients diagnosed as depressed. The number and proportion of these visits that
      included an antidepressant prescription or an anxiolytic prescription were
      determined. RESULTS: Primary care physicians and psychiatrists both prescribed
      antidepressants more commonly than other classes of psychotropic medications
      during visits that included a depression diagnosis. Compared with psychiatrists,
      primary care physicians more commonly prescribed antidepressants for depressive
      disorders (1980, 55% vs 33%; 1985, 59% vs 41%; 1989, 57% vs 45%). In 1989,
      benzodiazepines were prescribed in 16% of the primary care visits for depression.
      More than half of these visits (56%) also resulted in an antidepressant being
      prescribed. Primary care visits for depression tended to be slightly longer than
      other primary care visits, but only about half as long as patient visits with
      psychiatrists. CONCLUSIONS: The pharmacologic treatment of depression by primary
      care physicians may be better focused than previously assumed. Future research
      should examine the informal psychological treatment routinely provided by primary
      care physicians to patients with depressive disorders.

PMID- 1360491
TI  - A comparison of models used for calculation of RFLP pattern frequencies.
AB  - In recent years the application of DNA typing information to criminal
      investigations has gained widespread acceptance. The primary method currently in
      use relies on length variation of DNA restriction fragments between individuals.
      These variations are identified using variable number tandem repeat (VNTR) DNA
      probes. As this technology becomes more widely used, it is crucial that
      scientifically valid methods of interpreting the significance of a DNA typing
      result be adopted. The method chosen should not only give a reliable
      approximation of the statistical likelihood of a particular RFLP pattern
      occurring, but should also be easy to present and for the court to understand. In
      this manuscript five methods of calculating a frequency of occurrence of a RFLP
      pattern will be presented (fixed bin genotype, floating bin phenotype, floating
      bin genotype, National Research Council (NRC) method using fixed bins and the NRC
      method using floating bins). The calculations discussed here demonstrated that
      the fixed bin genotype method produces a frequency very similar to that obtained
      from floating bin phenotypes. In addition, regardless of the method chosen or the
      database size, the frequency of any particular banding pattern in the population
      over several loci was found to be very rare.

PMID- 1360492
TI  - Studies on Formosan soft corals. II. Cytotoxic cembranolides from the soft coral
      Lobophytum michaelae.
AB  - Bioactivity-guided fractionation of a CHCl3 extract of the soft coral Lobophytum
      michaelae afforded a new cytotoxic cembranolide, lobomichaolide (1), and a known
      cytotoxic cembranolide, crassolide (2). The structure of 1 was determined by
      spectral and X-ray crystallographic analysis.

PMID- 1360494
TI  - Proliferating cell nuclear antigen (PCNA) expression in Hodgkin's disease.
AB  - Previous studies of the proliferating cell fraction in Hodgkin's disease (HD)
      have been directed towards the classical Hodgkin and Reed-Sternberg cells (HRS)
      to the exclusion of the background population and have not included cases of
      nodular lymphocyte predominant Hodgkin's disease (NLPHD). Using an antibody to
      proliferating cell nuclear antigen (PCNA), we have determined the growth fraction
      of HRS cells and L&H cells in paraffin sections of 15 cases of classical HD [12
      nodular sclerosis (NS), 3 mixed cellularity (MC)] and eight cases of NLPHD. By
      double staining with anti-PCNA and antibodies to B cells (CD20) and T cells
      (CD45RO), we also determined the growth fraction and immunophenotype of the
      background population in each case. In classical HD, 50.4 per cent of HRS cells
      were PCNA-positive and judged to be proliferating, which is comparable to
      previous studies, while in NLPHD 76.9 per cent of L&H cells were PCNA-positive.
      In both classical HD and NLPHD, the majority of PCNA-positive cells in the
      background were T cells, which showed a growth fraction of 57.8 and 68.5 per
      cent, respectively; in comparison, only 4 per cent of B cells were PCNA-positive
      in each type of HD. L&H cells are widely accepted to be B cells and there is
      growing evidence that HRS cells are also B cell-derived. Our results underline a
      relationship between classical HD and NLPHD and suggest that the characteristic
      histological features of both diseases may be caused by the production and
      release of cytokines from altered B cells.

PMID- 1360493
TI  - Preventive medicine for HIV-infected patients: an analysis of isoniazid
      prophylaxis for tuberculin reactors and for anergic patients.
AB  - OBJECTIVE: To analyze the policies of isoniazid prophylaxis for human
      immunodeficiency virus (HIV)-infected tuberculin reactors and for HIV-infected
      anergic patients with unknown tuberculin status. METHODS: Transition-state model
      of clinical immune deterioration of HIV-infection over ten years, review of
      published data, and a survey of AIDS experts. Outcome measures are the numbers of
      tuberculosis cases and deaths prevented and isoniazid toxicity cases and deaths
      occurring with prophylaxis. PATIENTS: Hypothetical cohorts of HIV-infected 40
      year-olds. RESULTS: Because the tuberculosis activation rate is so high in HIV
      infected patients, the benefits of prophylaxis far outweigh the risks of
      isoniazid toxicity for tuberculin reactors with HIV infection at any stage of
      immune function: 1,469-2,868 tuberculosis cases and 170-274 deaths are prevented
      per 10,000 cohort over ten years, depending upon the cohort's initial immune
      state. The benefits of prophylaxis outweigh the risks of isoniazid toxicity for
      anergic HIV-infected patients if they come from a community with a 2% to 3% or
      greater prevalence of Mycobacterium tuberculosis infection. CONCLUSIONS:
      Isoniazid prophylaxis is a reasonable prevention measure for HIV-infected
      tuberculin reactors and for many HIV-infected anergic patients.

PMID- 1360495
TI  - Mitotic indices, anti-PCNA immunostaining, and AgNORs in thick cutaneous
      melanomas displaying paradoxical behaviour.
AB  - Those melanomas which fail to behave as expected from their Breslow thickness
      provide interesting material for study. In an attempt to explain differences in
      behaviour, we have evaluated three distinct proliferative markers in 23 thick
      melanomas which failed to metastasize and in 20 well-matched control tumours with
      documented metastasis. The test group demonstrated significantly greater numbers
      of mitoses when expressed as an index (mitoses per 1000 cells), whilst no
      difference was found when the results were expressed in terms of mitoses per unit
      area. Tumours showing epidermal ulceration possessed higher mitotic indices than
      those of non-ulcerated lesions. High fractions of PCNA immunolabelling combined
      with low mitotic indices were observed frequently in the non-metastasizing group.
      This result and its possible relation to survival advantage are discussed in
      detail. Both AgNOR numbers and patterns failed to act as prognostic variables-
      indeed, AgNORs failed to correlate with the other proliferative indices,
      suggesting that their value as a marker of tumour growth is severely limited.

PMID- 1360496
TI  - Diagnostic usefulness of dipeptidyl aminopeptidase IV monoclonal antibody in
      paraffin-embedded thyroid follicular tumours.
AB  - Monoclonal antibodies to dipeptidyl aminopeptidase IV (DAP IV, EC 3.4.14.5) were
      raised and selectively applied to paraffin-embedded sections of thyroid
      carcinoma. Five monoclonal antibodies were found to stain paraffin sections of
      thyroid carcinomas. Using one of these antibodies (44-4), we studied
      retrospectively aberrant expression of DAP IV in thyroid carcinoma to determine
      whether immunohistochemical staining with DAP IV antibody is useful in
      pathological diagnosis. In almost all cases of thyroid follicular and papillary
      carcinoma, tumour cells were positive (99.0 per cent) with DAP IV, whereas the
      cases of follicular adenoma showed a low incidence (27.1 per cent) of positive
      staining. Follicular adenoma with incomplete capsular invasion had a higher
      positive incidence (50 per cent) than follicular adenoma without incomplete
      capsular invasion (9.6 per cent). In positive staining cases previously diagnosed
      as benign tumours, 11 benign cases reacting positively with DAP IV were
      rediagnosed as carcinoma after re-examination of more thyroid paraffin block
      sections or serial sections. These findings suggest that DAP IV monoclonal
      antibody is very useful in distinguishing thyroid follicular carcinoma from
      follicular adenoma.

PMID- 1360497
TI  - In situ hybridization demonstrates the stability of mRNA in post-mortem rat
      tissues.
AB  - In situ hybridization was used to detect messenger RNA (mRNA) in a variety of rat
      tissues which were fixed in formalin either immediately after death or after a 24
      h period of storage at 5 degrees C. A synthetic polydeoxythymidine [poly d(T)]
      oligonucleotide probe was used to demonstrate polyadenylated [poly (A)] mRNA in
      the small intestine, pancreas, liver, cerebellum, and pituitary. Of these
      tissues, only the liver showed a small reproducible reduction in hybridization
      signal following delayed fixation. Synthetic oligonucleotide probes complementary
      to albumin and pro-opiomelanocortin (POMC) mRNAs were hybridized to liver and
      pituitary, respectively. There was no significant reduction in hybridization
      signal in post-mortem tissues. The results suggest that some mRNAs may be
      remarkably stable under certain post-mortem conditions and this should encourage
      the wider application of in situ hybridization techniques to post-mortem
      material.

PMID- 1360498
TI  - Proliferative activity determined by DNA flow cytometry and proliferating cell
      nuclear antigen (PCNA) immunohistochemistry as a prognostic factor in prostatic
      carcinoma.
AB  - Proliferative activity was measured in 165 paraffin-embedded prostatic carcinomas
      using DNA flow cytometric analysis of the S-phase (SPF) and G2/M-phase fractions
      and CAS 200 image analysis of the proliferating cell nuclear antigen (PCNA)
      expression defined immunohistochemically by PC10 and 19A2 monoclonal antibodies.
      No significant associations were found between the flow cytometric and the two
      immunohistochemical measures of cell proliferation. Of the four indices, only
      SPF, S + G2/M, and immunostaining with 19A2 antibody were associated with the
      poor histological grade of the tumour. High SPF and S + G2/M were significantly
      associated with poor 10-year overall survival (P < 0.001) and prostatic carcinoma
      specific survival (P < 0.01). Multivariate analyses of prostatic carcinoma
      specific survival in patients with non-metastatic disease (M0-stage) indicated
      that only S + G2/M, T-stage, and histological grade (only if re-evaluated by a
      single pathologist) had independent prognostic significance. High-level PCNA
      staining (> 16 per cent of cells stained) with 19A2 antibody was associated with
      poor prognosis only in univariate analysis, and PC10 immunostaining had no
      prognostic value. In conclusion, a high proliferative activity as defined by flow
      cytometric S+G2/M is an independent predictor of poor survival in patients with
      non-metastatic prostatic carcinoma. PCNA immunostaining from formalin-fixed,
      paraffin-embedded prostatic carcinomas has little, if any, prognostic value.

PMID- 1360500
TI  - Another cautionary note on the use of PCNA and AgNORs as markers for
      proliferation.

PMID- 1360499
TI  - Immunoreactivity of proliferating cell nuclear antigen compared with
      bromodeoxyuridine incorporation in normal and neoplastic rat tissue.
AB  - Monoclonal antibodies (MoAbs) against proliferating cell nuclear antigen (PCNA)
      represent a potentially useful tool for cell kinetic analysis of tumours. Because
      in paraffin-embedded tissue the relationship between PCNA immunoreactivity and
      tumour cell proliferation is not well characterized, we have compared PCNA
      positivity as detected by the PC10 MoAb with the bromodeoxyuridine labelling
      index (BrdUrd-LI) in two different transplantable hormone-dependent rat mammary
      tumours. Together, these two tumour models (MCR-83 and EMR-86) cover a wide range
      of S-phase fractions. Evaluating 31 methacarn-fixed tumours, a strong but non
      linear relationship (r = 0.98) was obtained. PCNA-positive fractions were
      invariably higher than corresponding BrdUrd-LIs and also higher than the
      estimated growth faction: growth fractions as determined by continuous BrdUrd
      labelling of the tumour and stromal cell population in EMR-86 carcinomas were 12
      and 26 per cent lower than PCNA-positive fractions, implying that a certain
      fraction of non-cycling cells can also express PCNA. A dramatic disturbance in
      the relationship of PCNA positivity and the BrdUrd-LI was observed in the EMR-86
      model after growth arrest induced by hormonal ablation: PCNA immunoreactivity
      remained detectable for at least 3 days, whereas the BrdUrd-LI decreased almost
      immediately. In comparison, PCNA immunoreactivity persisted for a much shorter
      period in small intestinal cells that had stopped DNA replication when moving
      from the crypt towards the villus. It is concluded that although differences in
      PCNA expression exist between various tissues, PCNA as detected by the PC10 MoAb
      may be used in tumours as an operational marker for the growth fraction.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1360501
TI  - Opioid properties of some derivatives of pethidine based on tropane.
AB  - The preparation of some tropane analogues of pethidine and its reversed ester,
      chiefly with preferred 3 alpha-m-hydroxyphenyl chair conformations, is described.
      The former were secured from tropan-3-one in a sequence of reactions involving
      cyanide attack, hydrolysis, Grignard attack and then rearrangements. The reversed
      ester was obtained by treating tropan-3-one with lithium phenyl, followed by
      acylation. Configurational and conformational assignments follow from NMR
      analysis. The antinociceptive potencies of these compounds in mice are reported,
      and discussed in relation to non-phenolic congeners and the 4-arylpiperidine
      moiety of morphine.

PMID- 1360502
TI  - Analogues of triprolidine: structural influences upon antihistamine activity.
AB  - The synthesis of some geometrical isomers related to triprolidine is reported.
      Previous configurational assignments, by UV and proton NMR, are validated by high
      field nuclear Overhauser enhancement methods and the isomeric purity of tested E-
      and Z-isomers was greater than 99.5% as assessed by an HPLC method developed for
      these compounds. Affinity constants for triprolidine (E and Z) in guinea-pig
      ileum showed a potency ratio of approximately 600 whereas at cerebellar sites
      this ratio was only approximately 100, suggesting that the H1 receptor in these
      two tissues may not be identical. In-vivo tests using a lethal dose of compound
      48/80 (a potent histamine-releasing agent) demonstrated that triprolidine itself
      was the most active compound to protect the animal among all the isomeric
      compounds tested: in all isomeric pairs the E-configuration possessed superior
      activity over Z. The disposition of the aryl groups in these geometrically
      constrained compounds mimics that seen in the structurally related chiral
      pheniramines which are sp3 hybridized and whose absolute stereochemistry is
      known.

PMID- 1360503
TI  - The plasma disposition and renal elimination of digoxin-specific Fab fragments
      and digoxin in the rabbit.
AB  - Administering digoxin-specific antibody fragments (DSFab, 1.9 mg kg-1, i.v.) to
      rabbits 1 h after digoxin (15 micrograms kg-1 or 12.5 microCi kg-1, i.v.)
      produced a redistribution of digoxin associated with a 5-fold elevation in total
      plasma concentration and 36-86% reductions in elimination half-life, apparent
      volume of distribution at steady-state and total body clearance (CLT). Renal
      clearance (CLR) was also reduced (54%), but urinary digoxin excretion was
      increased by one-third (35% vs 25%). This apparent anomaly is due to the large
      rise in total plasma digoxin concentration with a consequent increase in the area
      under the plasma concentration curve (AUC). The AUC, which is the denominator
      term in calculating CLR (and CLT), was increased to a greater extent than urinary
      digoxin excretion (numerator term in calculating CLR) so that an overall
      reduction in CLR occurred. The initial presence of digoxin appeared to alter the
      distribution of DSFab, since their plasma concentrations were markedly higher
      when the antibody was given after the hapten. The digoxin also reduced (from 3 to
      1%) the amount of detectable DSFab in the urine.

PMID- 1360504
TI  - Binding potency of paroxetine analogues for the 5-hydroxytryptamine uptake
      complex.
AB  - The in-vitro inhibition constants (Ki) of 14 structural analogues of the potent 5
      hydroxytryptamine (5-HT)-uptake inhibitor paroxetine were determined to assess
      the structure-affinity relationship of these derivatives. A goal of these studies
      was to determine those positions on paroxetine which could be derivatized without
      significantly decreasing the affinity of the drug for the binding site, so that
      radiolabels such as [18F]fluoroalkyl groups might be appended for future in-vivo
      imaging studies of the 5-HT uptake system. Using the methyl moiety as a steric
      probe for these studies, it was found that the rank order of potency of various
      methyl-substituted paroxetine analogues for inhibiting the binding of
      [3H]paroxetine to the 5-HT re-uptake site was: 4'-approximately equal to 3'
      approximately equal to 2''- > 2'-approximately equal to 1- > 5''- > 6''-methyl.
      The in-vitro equipotent molar ratios (EPMR, Ki(analogue)/Ki(paroxetine)) of the
      analogues were determined, and the EPMRs of the 4'-, 3'-, and 2''-methyl
      derivatives were 1.9, 2.2 and 2.2, respectively. The 4'- and 2''-fluoromethyl and
      -fluoroethyl analogues were synthesized, and the EPMRs of the 4'- and 2''
      fluoromethyl derivatives were determined to be 2.0 and 3.5, and those of the 4'-
      and 2''-fluoroethyl analogues were 5.2 and 6.2, respectively. The 2''
      fluoromethyl analogue was unstable in aqueous solutions, and it is not a
      promising ligand for in-vivo studies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360505
TI  - Plasma protein binding of quinine: binding to human serum albumin, alpha 1-acid
      glycoprotein and plasma from patients with malaria.
AB  - The binding of quinine to human serum albumin (HSA), alpha 1-acid glycoprotein
      (AAG) and plasma obtained from healthy subjects (10 caucasians and 15 Thais) and
      from Thai patients with falciparum malaria (n = 20) has been investigated. In
      healthy volunteers, plasma protein binding expressed as the percentage of unbound
      quinine was 7.9-31.0% (69-92.1% bound). The mean percentage of unbound quinine
      found with essentially fatty acid-free HSA (40 g L-1) was 65.4 +/- 1.5% (mean +/-
      s.d.) and was comparable with the value (66.3 +/- 3.8%, mean +/- s.d.) for
      Fraction V HSA (40 g L-1). This suggests that fatty acids do not influence the
      plasma protein binding of quinine. Binding of quinine to 0.7 g L-1 AAG was high
      (mean unbound 61.0 +/- 5.0%), indicating that quinine is bound primarily to AAG
      and albumin, although other plasma proteins such as lipoproteins may be involved.
      The mean percentage of unbound quinine was slightly less in caucasians (14.8 +/-
      6.7% unbound), compared with healthy Thai subjects (17.0 +/- 6.7% unbound). The
      higher binding of quinine in caucasian subjects was associated with a higher
      plasma AAG concentration observed in caucasians. Mean percentage of unbound
      quinine was significantly lower in Thai patients with malaria (10.9 +/- 4.0%)
      than in the healthy Thai subjects. The increase in the extent of quinine binding
      corresponded with the increase in the acute-phase reactant protein, AAG in the
      patients with malaria. Overall, when the data were combined there was a
      significant correlation (r = 0.846, P < 0.005) between the binding ratio
      (bound/unbound) of quinine and the plasma AAG concentration.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1360506
TI  - A rapid filtration assay for the glycine binding site on the NMDA receptor in rat
      cortical membranes using [3H]dichlorokynurenic acid.
AB  - A filtration binding assay using [3H]dichlorokynurenic acid to label the glycine
      binding site on the N-methyl-D-aspartic acid receptor has been evaluated on rat
      cortical membranes. This ligand binds to a single population of binding sites
      following mass action kinetics with a KD of 29 nM and a capacity of 5.73 pmol (mg
      protein)-1. The pharmacological specificity of the binding site is identical to
      that previously reported for this binding site using [3H]glycine as a
      radioligand. Agonists showed lower affinity and antagonists higher affinity when
      [3H]dichlorokynurenic acid was used compared with [3H]glycine. The higher
      affinity of [3H]dichlorokynurenic acid compared with [3H]glycine make it the more
      suitable compound with which to label the glycine site.

PMID- 1360507
TI  - Comparison of the effects of cromakalim in trachea isolated from normal and
      albumin-sensitive guinea-pigs.
AB  - The effects of the K(+)-channel activator, cromakalim, on spontaneous tone and
      constrictor responses to vagal stimulation or acetylcholine were compared in
      trachea isolated from groups of guinea-pigs that were: untreated; sensitized and
      chronically exposed to inhaled albumin; or sham sensitized. Responses were
      assessed as changes in intraluminal pressure in the isolated, Krebs-filled
      trachea, increases and decreases in intraluminal pressure directly reflecting
      constriction and dilatation, respectively. Cromakalim reduced resting
      intraluminal pressure in normal trachea but in sensitized trachea mixed effects
      occurred, many preparations exhibiting increases in intraluminal pressure,
      particularly at lower concentrations of cromakalim. Cromakalim attenuated the
      frequency-dependent increases in intraluminal pressure evoked by stimulation of
      the vagus nerve in a concentration-dependent manner and to a similar degree in
      trachea from each of the three groups tested. The degree of attenuation was
      similar in the absence and presence of the cyclo-oxygenase inhibitor
      flurbiprofen. In untreated trachea, responses to a range of concentrations of
      applied acetylcholine were attenuated by cromakalim. In sensitized trachea the
      response to the lowest concentration of applied acetylcholine was attenuated by
      cromakalim but responses to higher concentrations of were unaffected. The results
      indicate that the direct relaxant effect of cromakalim is altered in sensitized
      trachea, which may indicate abnormal K(+)-channel behaviour in the smooth muscle
      cell membrane. Attenuation by cromakalim of vagal responses occurs in both normal
      and sensitized trachea, due chiefly to a pre-junctional effect on cholinergic
      neurotransmission which is independent of the generation of cyclo-oxygenase
      products.

PMID- 1360508
TI  - Receptors involved in the modulation of 5-hydroxytryptamine release in bovine
      cerebral arteries.
AB  - The uptake of [3H]5-hydroxytryptamine (5-HT) in bovine cerebral arteries was
      reduced by cocaine (1 microM), ouabain (100 microM), pretreatment with 6
      hydroxydopamine (6-OHDA) (1.46 mM, 10 min) and metitepine (1 microM).
      Electrically-stimulated tritium release was decreased by tetrodotoxin (0.8
      microM), Ca-free medium, denervation with 6-OHDA (1.46 mM, 10 min), 5-HT (10
      microM), noradrenaline (1 microM) and the agonist of alpha 2-adrenoceptors B-HT
      920 (0.1 and 1 microM), enhanced by metitepine (1 microM, antagonists of
      presynaptic 5-HT1 receptors) and rauwolscine (1 microM, antagonist at alpha 2
      adrenoceptors, and also of 5-HT1D receptors) and not affected by ketanserin (1
      microM, antagonist of 5-HT2 receptors), methysergide (0.1 microM, antagonist of 5
      HT1 and 5-HT2 receptors) and phentolamine (1 and 3 microM antagonist of alpha
      adrenoceptors and less potent of 5-HT1 receptors). The inhibitory action of 10
      microM 5-HT was partially reversed by phentolamine (3 microM) and cocaine (1
      microM) and completely reversed by both metitepine (1 microM) and rauwolscine (1
      microM). Ketanserin (1 microM), methysergide (0.1 microM) or phentolamine (1
      microM) had no effect. Rauwolscine (1 microM) antagonized the inhibition induced
      by both noradrenaline (1 microM) and B-HT 920 (0.1 and 1 microM). 5-HT induced
      tritium release which was inhibited by cocaine (an antagonist of 5-HT3 receptors)
      and denervation with 6-OHDA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360510
TI  - The interaction between noradrenaline and ATP upon polyphosphoinositide
      metabolism and contraction in tail arteries from normo- and hypertensive rats.
AB  - The effects of, and interaction between, noradrenaline and alpha,beta-methylene
      ATP upon polyphosphoinositide (PPI) breakdown, investigated by measuring the
      accumulation of inositol phosphates, and contraction, were studied in tail
      arteries from normo- (WKY) and spontaneously-hypertensive (SHR) rats.
      Noradrenaline (10(-7)-10(-3) M) evoked a prazosin (10(-6) M)-sensitive,
      concentration-dependent increase in total inositol phosphate accumulation in both
      WKY and SHR rats. No significant differences were observed in either the maximal
      response or in the concentration range over which noradrenaline evoked this
      response, between these two populations. Noradrenaline (5 x 10(-7)-5 x 10(-5) M)
      evoked a concentration-dependent contraction of arteries from both SHR and WKY
      rats. The responses to noradrenaline were about 2-fold greater at all effective
      concentrations of noradrenaline in SHR compared with WKY rats. alpha,beta
      Methylene ATP (10(-6) M) did not alter noradrenaline-stimulated total inositol
      phosphate accumulation, in arteries from either SHR or WKY rats, measured either
      as the maximal response or as the EC50. alpha,beta-Methylene ATP (5 x 10(-6) M),
      by itself, evoked a contractile response, which was quantitatively similar in SHR
      and WKY rats, and was additive with the contractile responses to noradrenaline (5
      x 10(-7)-5 x 10(-5) M). The maximum response produced by a combination of
      noradrenaline and alpha,beta-Methylene ATP was quantitatively similar to that
      produced by noradrenaline alone. No evidence of synergism between alpha,beta
      Methylene ATP and noradrenaline upon contraction was observed.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1360509
TI  - Cardiovascular effects of LAS 30538, a new vascular selective Ca(2+)-channel
      blocker.
AB  - A new compound, 1-[2-(2,6-dimethylphenoxy)ethyl]-alpha,alpha-bis-(p-fluorphenyl)
      4 -piperidine methanol (LAS 30538), was found to have potent vasodilator effects.
      Its vasorelaxant activity was demonstrated in rat perfused hindlimbs contracted
      with 80 mM K+, having an IC50 value of 40 nM. In conscious spontaneously
      hypertensive rats, LAS 30538 administered orally, caused dose-dependent sustained
      falls in systolic blood pressure with an ED30 value of 11 mg kg-1. In pithed
      rats, LAS 30538, strongly inhibited vasoconstriction induced by the alpha 2
      adrenoceptor agonist B-HT 933 and the calcium agonist compound Bay K8644 with
      ED50 values of 4 mg kg-1 p.o. and 1.3 mg kg-1 i.v., respectively. Results from
      electrophysiological studies carried out using guinea-pig papillary muscles
      partially depolarized by 22 mM K+ are consistent with LAS 30538 acting as a
      Ca(2+)-channel blocker. When compared with verapamil, in guinea-pig and rabbit
      isolated heart preparations, LAS 30538 caused less cardiodepression and
      bradycardia. The results suggest that LAS 30538 may have some advantages over
      other Ca(2+)-channel blockers such as verapamil in causing less myocardial
      depression for a given level of vasodilatation.

PMID- 1360511
TI  - In-vivo pharmacological studies of 2-N-carboxamidinonormianserin, a histamine and
      5-hydroxytryptamine antagonist lacking central effects.
AB  - The in-vivo pharmacological properties have been examined of FCC5 (2-N
      carboxamidino-1,2,-3, 4, 10, 14b-hexahydrodibenzo (c.f.) pyrazino (1, 2
      alpha)azepine hydrochloride), a guanidino analogue of mianserin. FCC5 (30-100
      micrograms kg-1, i.v.) caused long-lasting (> 1 h) attenuation of histamine- and
      5-hydroxytryptamine (5-HT)-induced bronchoconstriction in the anaesthetized
      guinea-pig. FCC5 (< or = 1 mg kg-1, i.v.) had no effect on submaximal
      bronchoconstrictor responses caused by i.v. acetylcholine or the thromboxane A2
      mimetic U46619 ((15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E
      dienoic acid). The pressor effects of 5-HT in anaesthetized and pithed rats were
      inhibited by FCC5 (0.3-1.0 mg kg-1, i.v.). Higher doses of FCC5 (3 mg kg-1, i.v.)
      reduced bradycardia and depressor responses to 5-HT in anaesthetized rats. In
      anaesthetized cats and rats and also pithed rats, FCC5 (0.1-1.0 mg kg-1, i.v.)
      caused sympathomimetic effects as demonstrated by pressor responses and
      tachycardia. FCC5 (0.1-0.3 mg kg-1, i.v.) inhibited pressor responses to tyramine
      whereas those to noradrenaline and sympathetic nerve stimulation were
      potentiated. Oedema in the rat paw caused by intraplantar 5-HT was inhibited by
      FCC5 (ID50 0.76 mg kg-1, i.p.; and 2.7 mg kg-1, p.o.). In decerebrate rats which
      had been spinalized at T6-8, fenfluramine-induced facilitation of the flexor
      reflex of the anterior tibialis muscle was inhibited by mianserin (ID50 0.36 mg
      kg-1, i.p.) but not by FCC5 (< or = 3 mg kg-1, i.p.).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1360512
TI  - The effect of serum Ca2+ compensation on the efficacy of chlorpropamide in
      alloxan-diabetic rabbits.
AB  - A decrease in serum Ca2+ concentration was observed in alloxan-diabetic rabbits,
      with recovery of serum Ca2+ levels achieved following insulin therapy. This
      suggested that the diabetic condition directly relates to the decrease in serum
      Ca2+ levels. The efficacy of chlorpropamide in alloxan-diabetic rabbits after
      intravenous injection (150 mumol kg-1) was less than that in normal rabbits as
      measured by the serum insulin levels, and the efficacy did not change when the
      dose was increased. However, compensation of serum Ca2+ levels in alloxan
      diabetic rabbits caused an increase in the efficacy of chlorpropamide observed as
      an increase in serum insulin and a decrease in serum glucose levels.

PMID- 1360513
TI  - The calcium channel blocker LAS 30538, unlike nifedipine, verapamil, diltiazem or
      flunarizine, potently inhibits insulin secretion in-vivo in rats and dogs.
AB  - The effects of a novel calcium channel blocker, LAS 30538 (1-[2-(2,6
      dimethylphenoxy)ethyl]-alpha,alpha-bis-(p-fluorophenyl)-4- piperidine methanol),
      were studied on glucose tolerance and insulin secretion in rats and dogs in-vitro
      and in-vivo. Some comparisons were made with nifedipine, verapamil, diltiazem,
      flunarizine, diazoxide, cromakalim and minoxidil. LAS 30538, like a number of
      calcium channel blockers, was found to inhibit insulin secretion in-vitro, but
      was 1000-fold more potent than verapamil or diltiazem in this respect. LAS 30538
      differed from the other calcium channel blockers studied in that it also potently
      inhibited insulin secretion and impaired glucose tolerance in-vivo. The evidence
      that LAS 30538 is more potent than diazoxide as a hyperglycaemic agent in-vivo
      suggests that this could be a useful drug for the treatment of hyperinsulinaemia
      in man.

PMID- 1360514
TI  - Effect of mammalian lignans on fMLP-induced oxidative bursts in human
      polymorphonuclear leucocytes.
AB  - We examined the effects of mammalian lignans, enterolactone, prestegane B and 2,3
      dibenzylbutane-1,4-diol (DBB) on superoxide production and luminol-dependent
      chemiluminescence (LCL) response in human polymorphonuclear leucocytes (PMNs).
      The three lignans had no direct effect on the responses of human PMNs. DBB and
      prestegane B enhanced the superoxide production and LCL response induced by
      formylmethionyl-leucyl-phenylalanine (fMLP), but enterolactone inhibited fMLP
      induced effects. The effects of DBB were stronger than those of prestegane B and
      the effects of DBB were inhibited by bromophenacyl bromide, mepacrine, N-(6
      aminophenyl)-5-chloro-1-naphthalene, sulphonamide and trifluoroperazine, but not
      by gossypol, nordihydroguaretic acid, indomethacin, staurosporine, 1-(5
      isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride or (R,S)-2-methoxy-3
      (octadecyl-carbamoyloxy)-propyl-2-(2-thiazoli o)-ethylphosphate. These results
      suggest that DBB primes the responses of human PMNs, and the priming effect is
      caused by the activation of phospholipase A2--and Ca(2+)-calmodulin-pathways, but
      not by the activation of lipoxygenase, cyclo-oxygenase and protein kinase C or by
      the release of platelet activating factor.

PMID- 1360515
TI  - Effects of cupric chloride and tamrabhasma, a traditional Indian preparation of
      copper, on eicosanoid production by human gastric and colonic mucosa.
AB  - Tamrabhasma is a traditional copper oxide-containing Indian preparation which has
      anti-ulcer activity. We have studied the effect of tamrabhasma and CuCl2.2H2O on
      prostaglandin formation by human gastric and colonic mucosa and submucosa, as
      prostaglandins have mucosal protective activity, and their release may contribute
      to the anti-ulcer effect. With the gastric mucosa, tamrabhasma 10 micrograms mL
      1, but not 0.1 or 1 microgram mL-1, increased prostaglandin E (PGE) concentration
      by 38% (P < 0.05), with little or no effect on 6-keto-PGF1 alpha, thromboxane B2
      or the leukotriene (LT) LTC4/LTD4. CuCl2.2H2O (10 micrograms mL-1) increased 6
      keto-PGF1 alpha by 46% (P < 0.05), but 0.1, 1, 50 and 250 micrograms mL-1 did not
      significantly affect any of the prostanoids, and only the highest concentration
      reduced the amount of LTC4/LTD4. In the colon mucosa, tamrabhasma (0.1-10
      micrograms mL-1) or CuCl2.2H2O (10-50 micrograms mL-1) increased all the
      prostanoids and this effect was greater than in the gastric mucosa but there was
      no significant change in LTC4/LTD4. CuCl2.2H2O showed a bell-shaped concentration
      effect curve, with no significant effect at lower and higher amounts.
      Indomethacin (0.1-10 micrograms mL-1) caused a concentration-dependent reduction
      in the prostanoid amounts. The effect of tamrabhasma was probably not only due to
      the presence of Cu2+, as tamrabhasma was more effective than CuCl2.2H2O alone; in
      addition the solubility of CuO is very low. Increased prostanoid levels might
      explain, at least partly, the gastric mucosal protection by tamrabhasma. The
      results in the colon, however, raise the possibility that tamrabhasma should be
      examined for the treatment of inflammatory bowel disease.

PMID- 1360516
TI  - Microsomal formation of N-benzyl-4-hydroxymethylaniline from N-benzyl-4
      methylaniline.
AB  - The in-vitro metabolism of N-benzyl-4-methylaniline was re-examined using male
      hamster and rabbit hepatic microsomes; both species generated N-benzyl-4
      hydroxymethylaniline, confirmed by TLC and HPLC, comparison with authentic
      compound. Further confirmation of the formation of this metabolite was achieved
      by use of a rapid scan UV detector.

PMID- 1360517
TI  - Digoxin-specific Fab fragments impair renal function in the rabbit.
AB  - A 2 mg kg-1 intravenous bolus dose of digoxin-specific Fab fragments produced a
      28% reduction in creatinine clearance in rabbits after 24 h. Urine output was
      reduced, while plasma and urinary creatinine concentrations were unaffected and
      increased, respectively. By 5 days the creatinine clearance had returned to
      normal. The fractional excretion of Na+ was nearly halved, indicating that the
      tubular reabsorption of Na+ increased to compensate for the reduced glomerular
      filtration rate, suggesting that tubular (as opposed to glomerular) function was
      not impaired.

PMID- 1360518
TI  - Statistical assessment of the synergistic effect between a vaccine and a drug.

PMID- 1360519
TI  - Non-Michaelis-Menten type hepatic uptake of liposomes in the rat.
AB  - The objective of this study was to verify the methodology for measuring uptake
      clearance of liposomes and to characterize kinetically the saturable hepatic
      uptake of liposomes-through phagocytosis. The correction of vascular space was
      important in the evaluation of hepatic uptake. The efflux of liposomes from liver
      was shown to be negligible, by a repeated dose study, and thus, hepatic clearance
      can be obtained by the hepatic uptake divided by the area under the blood
      concentration-time curve (AUC). The determinant parameter which describes the
      saturability of uptake clearance of liposomes, independent of infusion rate, was
      investigated, using the data of an in-vivo constant infusion study, where
      infusion rate-dependent saturable hepatic clearance was observed. The mean blood
      concentration failed to obtain an infusion rate-independent function. On the
      other hand, the AUC could explain the saturability of hepatic clearance for every
      infusion rate by a unique relationship. The hepatic uptake amount could also
      explain this saturability, independent of infusion rate. These kinetic
      characteristics are inconsistent with Michaelis-Menten type kinetics, therefore a
      new model is required to describe the saturable hepatic clearance in the
      disposition of liposomes.

PMID- 1360521
TI  - Improvement of intestinal absorption of thyrotropin-releasing hormone by chemical
      modification with lauric acid.
AB  - Intestinal absorption of 125I-labelled lauryl thyrotropin-releasing hormone (Lau
      TRH), a novel lipophilic derivative of TRH, was examined by rat in-situ closed
      intestinal loops. At a dose of 1 mumol per rat into the small intestine, a
      significant increase in percent of dose in plasma radioactivity of Lau-TRH was
      observed in comparison with that of TRH. A dose-dependent decrease in percent of
      dose in plasma radioactivity of TRH was noted, suggesting a saturable process of
      TRH transport. In contrast, the percent of dose in plasma radioactivity of Lau
      TRH increased with increasing dose of Lau-TRH. The stability of TRH and Lau-TRH
      was studied in plasma and rat small intestinal homogenates. Lau-TRH was more
      stable than TRH in rat plasma. These results suggest that chemical modification
      of TRH with lauric acid may not only increase the lipophilicity of TRH but also
      reduce the degradation of TRH, resulting in the increased plasma radioactivity of
      TRH. On the other hand, Lau-TRH was gradually converted to TRH in the intestinal
      mucosal homogenate. These findings indicate that chemical modification of TRH
      with lauric acid might be a useful approach for improving the intestinal
      absorption of this peptide.

PMID- 1360520
TI  - A novel prodrug of salicylic acid, salicylic acid-glycylglycine conjugate,
      utilizing the hydrolysis in rabbit intestinal microorganisms.
AB  - The hydrolysis of salicylic acid-glycylglycine conjugate (salicyl-glycylglycine)
      following oral, intravenous, intracaecal and rectal administration (434, 72, 36
      and 36 mumol kg-1, respectively: equivalent to salicylic acid) was examined in
      rabbits to develop a novel prodrug of salicylic acid. Salicylic acid was detected
      in the blood 2 h after oral administration of salicyl-glycylglycine and it
      reached a maximum level (55.6 micrograms mL-1) at 15 h, whereas a small amount of
      salicyl-glycylglycine was found in the blood. In contrast, unchanged salicyl
      glycylglycine was found mainly in the blood following its intravenous
      administration, suggesting the involvement of presystemic deconjugation in the
      hydrolysis of salicyl-glycylglycine. Immediate and very extensive salicyclic acid
      formation in the caecum was observed following intracaecal administration of
      salicyl-glycylglycine, suggesting that the intestinal microorganisms were
      responsible for the biotransformation of this compound. In-vitro incubation of
      salicyl-glycylglycine with caecal content showed that salicyl-glycylglycine was
      hydrolysed efficiently in the caecum. Consequently, the blood concentration of
      salicylic acid was prolonged extensively following rectal administration of
      salicyl-glycylglycine, indicating the usefulness of salicyl-glycylglycine as a
      prodrug of salicylic acid.

PMID- 1360522
TI  - The pH dependent uptake of enoxacin by rat intestinal brush-border membrane
      vesicles.
AB  - The mechanism of the intestinal transport of enoxacin, an orally active
      fluoroquinolone antibiotic, has been investigated using brush-border membrane
      vesicles isolated from rat small intestine. The initial rate and time-course of
      enoxacin uptake were considerably dependent upon the medium pH (pH 5.5 greater
      than pH 7.5) and upon the percent ionization of the carboxyl group (pKa 6.2,
      anionic charge), namely, the degree of uptake of cationic form was higher than
      that of the zwitterionic form. There was evidence of transport into the
      intravesicular space as shown by the effect of extravesicular medium osmolarity
      on enoxacin uptake at steady state (30 min). This transport across the brush
      border membrane was stimulated by the valinomycin-induced K(+)-diffusion
      potential (interior negative) and an outward H(+)-diffusion potential.
      Furthermore, changing the pH of the medium from 5.5 to 7.5 significantly
      decreased the effect of valinomycin-induced K(+)-diffusion potential on the
      enoxacin uptake. These results suggest that the uptake behaviour of the cationic
      form of enoxacin plays an important role in the intestinal absorption process of
      enoxacin.

PMID- 1360523
TI  - Alpha 1-adrenoceptor subtypes in bovine prostate.
AB  - The object of this study was to examine the existence and characteristics of
      alpha 1-adrenoceptor subtypes in the bovine prostate using the radioligand
      binding assay method. [3H]Prazosin was used as the radioligand and its binding
      sites in bovine prostate were classified into two subtypes. One subtype showed a
      high affinity (alpha 1High, Kd: 101.1 pM and Bmax: 11.8 fmol (mg protein)-1) and
      the other had a low affinity (alpha 1Low, Kd: 3371.4 pM and Bmax: 50.5 fmol (mg
      protein)-1). Although the same pKi values of clorethylclonidine, p
      aminoclonidine, benoxathian and dibenamine to both alpha 1High and alpha 1Low
      binding sites in bovine prostate tissue were observed, other alpha 1 antagonists
      used in this study had different pKi values for the two alpha 1-adrenoceptor
      subtypes. The existence and binding characteristics of alpha 1-adrenoceptor
      subtypes in bovine prostate were clarified. It is possible that agents selective
      for one site may contribute to the development of better drugs for the treatment
      of bladder outlet obstructions of men with benign prostatic hyperplasia.

PMID- 1360524
TI  - Inhibitory effects of tiamulin on contractile and electrical responses in
      isolated thoracic aorta and cardiac muscle of guinea-pigs.
AB  - The inhibitory effect of tiamulin, an antibiotic produced by Pleurotus mutilis,
      on contractile and electrical responses in isolated thoracic aorta and cardiac
      muscle of guinea-pigs was studied. In the thoracic aorta, tiamulin with an IC50
      of 9.7 x 10(-6) M inhibited sustained contractions induced by isosmotically added
      60 mM KCl. The inhibitory effect of tiamulin on a Ca(2+)-induced contraction in a
      depolarized muscle was competitively antagonized by raising external Ca2+
      concentration. Bay K 8644 (10(-7) M) antagonized tiamulin's inhibition of the
      Ca(2+)-induced contraction. Tiamulin (2 x 10(-5) M) decreased the elevated
      cytoplasmic Ca2+ level measured by the fura 2 AM method in the depolarized
      muscle. In high K(+)-isoprenaline-treated left atria, tiamulin (2 x 10(-5)-2 x
      10(-4) M) produced negative inotropic effects. On the other hand in the membrane
      action potential of papillary muscles, tiamulin (2 x 10(-6)-2 x 10(-4) M)
      produced decreases in action potential and durations and 2 x 10(-4) M tiamulin
      depressed the slow response action potential in depolarized muscles. Tiamulin
      produced prolongations of the PR interval in ECG, negative chrono- and inotropic
      effects, and an increase in perfusion flow in guinea-pig isolated and perfused
      hearts. These effects of tiamulin on the aorta or cardiac muscle were similar to
      those of verapamil and nifedipine. These results suggest that both the inhibitory
      action of tiamulin on the high K(+)-induced contraction in the aorta and the
      negative inotropic effect of tiamulin on the cardiac muscle are due to an
      inhibition of Ca2+ entry through the voltage-dependent Ca2+ channels of cells of
      both these muscles.

PMID- 1360526
TI  - Relationship between paracetamol plasma levels and its analgesic effect in the
      rat.
AB  - The relationship between plasma levels of paracetamol and its analgesic effect
      was studied in the rat using a model of pain-induced functional impairment
      (PIFI). Female Wistar rats received an intraarticular injection of 30% uric acid
      in the knee of the right hind limb, inducing its dysfunction. Animals then
      received oral paracetamol at doses of 178, 316 or 562 mg kg-1 and the recovery of
      functionality over time was considered as an expression of analgesia. Paracetamol
      plasma levels were determined by HPLC. Results showed that there is a direct
      relationship between paracetamol plasma levels and its analgesic effect that
      follows a sigmoidal model according to the Hill equation. The PIFI model appears
      to be a useful tool to establish pharmacokinetic/pharmacodynamic relationships
      for non-narcotic analgesics.

PMID- 1360525
TI  - Feverfew extracts and parthenolide irreversibly inhibit vascular responses of the
      rabbit aorta.
AB  - Samples prepared from chloroform extracts of fresh leaves of feverfew (Tanacetum
      parthenium) strongly inhibited responses of rabbit aortic rings to phenylephrine,
      5-hydroxytryptamine, thromboxane mimetic U46619 (9,11-dideoxy-11 alpha,9 alpha
      epoxy-methano-PGF2 alpha), and angiotensin II, but the inhibition to contractions
      induced by potassium depolarization was much less. The inhibition was
      concentration- and time-dependent, non-competitive, and irreversible, and also
      occurred in endothelium-denuded preparations. The feverfew extracts also caused a
      progressive loss of tone of pre-contracted aortic rings and appeared to impair
      the ability of acetylcholine to induce endothelium-dependent relaxations of the
      tissue. These effects were mimicked by a purified preparation of an alpha
      methylenebutyrolactone, parthenolide, obtained from the extract. Our results
      demonstrate a nonspecific and potentially toxic response to feverfew on the
      vasculature.

PMID- 1360527
TI  - Nicotinate esters: their binding to and hydrolysis by human serum albumin.
AB  - Nicotinate esters were studied for their binding to, and hydrolysis by, human
      serum albumin. Some esters (ethyl, isopropyl, t-butyl, cyclohexyl, benzyl) were
      bound but not hydrolysed, while others (2-chloroethyl, 2-butoxyethyl) displayed
      the opposite behaviour; 1-carbamoylethyl ester was neither bound nor readily
      hydrolysed. Only p-methoxyphenyl nicotinate was both a ligand and a substrate,
      and its rate constants of binding and hydrolysis were calculated in a stepwise
      procedure using a kinetic model.

PMID- 1360528
TI  - Single- and multiple-dose pharmacokinetics of nefiracetam, a new nootropic agent,
      in healthy volunteers.
AB  - The pharmacokinetic profile of nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1
      pyrrolidinyl)acetamide), a new nootropic agent, was studied in healthy Japanese
      male volunteers. Nefiracetam was administered orally at doses of 10-200 mg in the
      single-dose studies, and at doses of 200 mg three times a day for seven days in
      the multiple-dose study. An HPLC method was used to determine the concentrations
      of nefiracetam in serum, urine and faecal samples. Linear kinetic behaviour was
      obtained after single oral administration. Serum concentrations of nefiracetam
      reached maximum values (Cmax) within 2 h for all dosage groups, and declined
      monophasically after Cmax with half-lives of 3-5 h. The area under the
      concentration-time curve (AUC infinity) and Cmax were linearly related to the
      dose. The apparent clearance (CL) values were 94.4-140.3 mL min-1. Urinary
      excretion of nefiracetam was independent of the administered dose, and less than
      10% of the dose was recovered in urine as the unchanged form within 24 h after
      administration. Renal clearance (CLR) did not change significantly as dose
      increased from 10 to 1200 mg. Faecal excretion of nefiracetam was less than 0.1%
      of the dose up to 24 h after a 300 mg oral dose. Food intake delayed the
      absorption of nefiracetam but did not significantly modify its pharmacokinetics.
      No clinically significant accumulation of nefiracetam in the body was observed
      during and after multiple doses.

PMID- 1360529
TI  - Phenobarbitone population pharmacokinetics from routine clinical data: role of
      patient characteristics for estimating dosing regimens.
AB  - Routine clinical pharmacokinetic data collected from patients receiving
      phenobarbitone have been analysed to evaluate the role of patient characteristics
      for estimating dosing regimens. The data were analysed using NONMEM, a computer
      program designed for population pharmacokinetic analysis that allows pooling of
      data. The pharmacokinetic model of phenobarbitone was described using a one
      compartment steady-state model. The effect of a variety of developmental and
      demographic factors on clearance was investigated. NONMEM estimates indicated a
      nonlinear function of total body weight as the optimum adjustment of
      phenobarbitone clearance. Concomitant administration of phenobarbitone and other
      antiepileptic drugs showed a decrease of phenobarbitone clearance in young
      children. The dosing method based on clearance values obtained by NONMEM analysis
      allowed the prediction of the steady-state concentration as a function of
      maintenance dose with acceptable error for therapeutic drug monitoring.

PMID- 1360530
TI  - Digoxin population pharmacokinetics from routine clinical data: role of patient
      characteristics for estimating dosing regimens.
AB  - Routine clinical pharmacokinetic data collected from patients receiving digoxin
      have been analysed to evaluate the role of patient characteristics for estimating
      dosing regimens. The data were analysed using NONMEM, a computer program designed
      for population pharmacokinetic analysis that allows pooling of data. The
      pharmacokinetic model of digoxin was described using a one-compartment steady
      state model. The effect of a variety of developmental and demographic factors on
      clearance was investigated. NONMEM estimates indicate that digoxin clearance was
      influenced by the demographic variables of age, total body weight, serum
      creatinine and sex. The interindividual variability in digoxin clearance was
      modelled with additive error with an estimated standard deviation of 46.15 L day
      1 and the intraindividual variability, or residual error was 0.209 ng mL-1. The
      dosing method based on clearance values obtained by NONMEM analysis allowed the
      prediction of the steady-state concentration as a function of maintenance dose
      with acceptable error for therapeutic drug monitoring.

PMID- 1360531
TI  - Distribution of antipyrine in the rat liver.
AB  - The rate and extent of hepatic distribution of antipyrine was examined in the rat
      isolated perfused liver. Tritiated water and [14C]antipyrine were injected
      simultaneously into the portal vein as a bolus using either Krebs-Ringer
      bicarbonate or rat plasma as the perfusate. The effluent profiles of each
      compound using the two perfusates were superimposable, a finding expected for
      water and consistent for antipyrine, which was negligibly bound in rat plasma.
      Although full recovery (97%) of administered material was achieved with both
      compounds, the fractional output profile for antipyrine peaked at a lower value
      (0.10 mL-1) and at a later time (24 s) than water (0.14 mL-1, 17.5 s), due to
      antipyrine having a larger volume of distribution (water 0.61 mL (g liver) -1);
      antipyrine 0.81 mL (g liver)-1). This observation is explained by antipyrine
      binding to, or partitioning into cellular components. Nonetheless, like water,
      distribution of antipyrine into hepatic cells is perfusion rate limited as
      evidenced by the superimposition of the dimensionless plots of fractional output
      vs time normalized to mean residence time.

PMID- 1360532
TI  - Dissolution and absorption of caffeine from guarana.
AB  - The rate of release of caffeine from capsules of guarana was compared with that
      from capsules containing an equivalent amount of caffeine using the British
      Pharmacopoeia dissolution test apparatus. Determinations were carried out in
      media of pH 2 and 6.8 and caffeine concentrations in the dissolution fluid were
      determined by HPLC. No significant differences in release rates were found
      between the two preparations at either pH. The rate of absorption of caffeine
      across rat intestine using the everted gut was also compared for a guarana
      suspension and a solution containing an equivalent amount of caffeine.
      Experiments were carried out using fluids of pH 4.0 and 7.4. No significant
      differences in absorption between the two preparations were observed. These
      results show that the release and uptake of caffeine from guarana is the same as
      for preparations containing free caffeine.

PMID- 1360533
TI  - PAF formation by human gastrointestinal mucosa/submucosa in-vitro: release by
      ricinoleic acid, and inhibition by 5-aminosalicylic acid.
AB  - Human isolated gastrointestinal mucosa/submucosa incubated with ricinoleic acid
      (12.5-100 micrograms mL-1) or the calcium ionophore A23187 (10 micrograms mL-1)
      released platelet-activating factor (PAF) as determined by a scintillation
      proximity assay after extraction and purification. 5-Aminosalicylic acid (25-100
      micrograms mL-1) inhibited PAF release by ricinoleic acid in a concentration
      dependent manner, and 50 micrograms mL-1 reduced the effect of A23187. We suggest
      that PAF may play a role in the laxation and mucosal damage by ricinoleic acid
      released from castor oil.

PMID- 1360534
TI  - Nifedipine-morphine interaction: a further investigation on nociception and
      locomotor activity in mice.
AB  - Nociception and locomotor activity were tested in mice (C57BL/6 and DBA/2
      strains), receiving the dihydropyridine calcium-channel blocker nifedipine, alone
      or combined with morphine. The calcium antagonist did not change the reaction
      time to thermal stimulation (tail-flick test), when administered alone, but
      combinations of nifedipine and morphine prolonged tail-flick latencies less than
      did the opiate alone. Nifedipine decreased locomotion in both strains, reduced
      the hypermotility induced by morphine in C57 mice, and enhanced the locomotor
      depression induced by the opiate in DBA mice. A comparison of the effects of
      nifedipine with those of the non-calcium antagonist vasodilator, hydralazine,
      suggests that the interactions with morphine were not exclusively related to
      neuronal changes produced by calcium channel blockade, but also to haemodynamic
      factors. In fact, except for the lack of interference with morphine-induced
      hypermotility in C57 mice, hydralazine, given alone or in combination with
      morphine, produced effects similar to those of nifedipine.

PMID- 1360535
TI  - Stimulation of postsynaptic 5-HT1A receptors is responsible for the anticonflict
      effect of ipsapirone in rats.
AB  - Ipsapirone (1.25-10 mg kg-1), a non-benzodiazepine anxiolytic drug with high
      affinity for 5-hydroxytryptamine1A (5-HT1A) receptors, increased dose-dependently
      the number of punished licks in the drinking conflict test (Vogel test) in rats.
      The anticonflict effect of the drug administered at a dose of 5 mg kg-1 was not
      modified in animals with lesions of 5-HT neurones, produced by p
      chloroamphetamine (PCA, 2 x 10 mg kg-1). The anticonflict effect of ipsapirone in
      PCA-pretreated rats was antagonized by the 5-HT1A receptor and alpha 1
      adrenoceptor antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2
      phthalimmido)]butylpiperazine hydrobromide; 0.5-1 mg kg-1), but not by the
      selective alpha 1-adrenoceptor blocker prazosin (0.5 mg kg-1). Neither NAN-190
      nor prazosin affected the punished response in PCA-pretreated rats. The present
      results indicate that the anticonflict effect of ipsapirone depends on
      stimulation of postsynaptic 5-HT1A receptors.

PMID- 1360536
TI  - BQ-153, a novel endothelin (ET)A antagonist, attenuates the renal vascular
      effects of endothelin-1.
AB  - Endothelin (ET)-1, leukotriene D4 and the thromboxane analogue, U-44069, were all
      shown to produce dose-dependent reductions in renal blood flow after direct
      injection into the renal artery of anaesthetized pigs. The effects of ET-1
      differed from the other two mediators in that ET-1 caused a transient vasodilator
      followed by a prolonged vasoconstrictor response. The pressor response was not
      mediated by the secondary release of either leukotriene D4 or thromboxane A2 as
      evidenced by the lack of effect of appropriate receptor antagonist MK571 (3-[-2(7
      chloro-2 quinolinyl) ethenyl]phenyl[3-(dimethylamino-3-oxopropyl)thio]methyl thio
      propionic acid) and L-670,596 respectively. This response, however, could be
      inhibited in a dose-dependent fashion by the selective ETA antagonist, BQ-153
      (cyclo-D-sulphalanine-L-Pro-D-Val-L-Leu-D-Trp-). Following blockade by BQ-153 the
      vasodilator response was unaffected and a residual pressor response remained,
      suggesting that either or both of these effects were mediated either through an
      ETB or a novel, as yet undefined, endothelin receptor.

PMID- 1360537
TI  - NaF and two other esterase inhibitors unaffect acetyl salicylic acid enzyme
      hydrolysis.

PMID- 1360539
TI  - Society for the Study of Fertility. British Fertility Society. Joint meeting.
      Bristol, 16-18 December 1992. Abstracts.

PMID- 1360538
TI  - Immune activation markers and CD4+ T-cell counts in HIV-infected intravenous drug
      users.

PMID- 1360540
TI  - The P-glycoprotein gene family of Caenorhabditis elegans. Cloning and
      characterization of genomic and complementary DNA sequences.
AB  - P-glycoproteins, encoded by families of evolutionarily conserved genes, can
      confer a multidrug-resistant phenotype to mammalian tumor cells. To obtain more
      information on their functions in normal cells we have cloned genomic and
      complementary DNA sequences of four P-glycoprotein gene homologs of the
      genetically well-characterized nematode Caenorhabditis elegans, termed pgp-1, pgp
      2, pgp-3 and pgp-4, respectively. The genes were physically mapped on chromosome
      IV (pgp-1), I (pgp-2) and X (pgp-3 and pgp-4). Phenotypic mutants corresponding
      to these loci have not yet been described. Two of the genes, pgp-1 and pgp-3,
      were analyzed in detail. They are predicted to encode ATP-binding membrane
      spanning proteins of 1321 and 1254 amino acid residues, respectively, with the
      characteristic features shared by most P-glycoproteins described thus far. Intra
      species divergence of P-glycoprotein genes is more pronounced in C. elegans than
      in mammals. Only 40% of the amino acids of pgp-1 and pgp-3 are identical, in
      contrast to 77% identity between human MDR1 and MDR3. pgp-1 consists of 14 exons,
      pgp-3 of 13. The two genes share only one intron position, whereas they share
      four (pgp-1) and five (pgp-3) intron positions with mammalian P-glycoprotein
      genes. pgp-1, pgp-2, and pgp-3 are transcribed into low abundance mRNAs in wild
      type nematodes. pgp-1 and pgp-3 mRNAs have the trans-spliced leader SL1 at their
      5' ends. Arsenite, emetine and actinomycin D drugs did not increase the steady
      state levels of pgp mRNA, unlike in some mammalian cell types. Heat shock
      disturbed trans as well as cis-splicing of pgp-1 and led to the accumulation of
      partially processed pgp-1 RNA. Thus, in C. elegans these genes are not induced in
      the context of a general stress response, as has been proposed for mammalian P
      glycoprotein genes in certain tissues.

PMID- 1360541
TI  - Cold-induced alterations in the binding of adrenomedullary nuclear proteins to
      the promoter region of the tyrosine hydroxylase gene.
AB  - It is well documented that cold stress induces a rapid trans-synaptically
      mediated increase in the relative abundance of rat adrenomedullary tyrosine
      hydroxylase (TH) mRNA. To investigate the transcriptional mechanisms regulating
      the cold stress response, we have employed a gel mobility shift assay, using DNA
      fragments prepared from the proximal 5' flanking region of the bovine TH gene as
      a heterologous molecular probe. In pilot studies, this region of the bovine TH
      promoter (nucleotides -246 to +21) was fused to the bacterial reporter gene,
      chloramphenicol acetyltransferase, and the chimeric construct transfected into
      human neuroblastoma SK-N-BE(2)-C, hepatoma HepG2, and rat pheochromocytoma PC-12
      cells. Results of this analysis indicate that the proximal 5' flanking region of
      the bovine TH gene contains sufficient information to drive transient reporter
      gene expression in both human and rat catecholaminergic clonal cell lines. The
      findings derived from the gel mobility shift studies demonstrate that cold
      exposure causes rapid and selective alterations in the binding of adrenomedullary
      nuclear proteins to the proximal 5' flanking region of the TH gene. The most
      striking cold stress-induced alteration in DNA/nucleoprotein binding occurs in a
      region of the TH promoter (nucleotides -246 to -189) which contains an element
      bearing marked sequence similarity to an AP1 binding site and is highly conserved
      among animal species. This alteration occurs within 1 hr of cold exposure and
      persists for up to 48 hr after the onset of stress. The results of adrenal
      denervation experiments indicate that the cold-induced change in
      DNA/nucleoprotein binding is neurally mediated, requiring intact sympathetic
      innervation of the gland.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360542
TI  - Tau protein induces bundling of microtubules in vitro: comparison of different
      tau isoforms and a tau protein fragment.
AB  - Expression of tau protein in non-neuronal cells can result in a redistribution of
      the microtubule cytoskeleton into thick bundles of tau-containing microtubules
      (Lewis et al.: Nature 342:498-505, 1989; Kanai et al.: J Cell Biol 109:1173-1184,
      1989). We reconstituted microtubule bundles using purified tubulin and tau in
      order to study the assembly of these structures. Taxol-stabilized tubulin
      polymers were incubated with various concentrations of recombinant human tau and
      examined by electron microscopy. With increasing concentrations of tau 3 (tau
      isoform containing three microtubule binding domains) or tau 4 (isoform
      containing four microtubule binding domains) the microtubules changed orientation
      from a random distribution to loosely and tightly packed parallel arrays and then
      to thick cables. In contrast, tau 4L, the tau isoform containing four microtubule
      binding domains plus a 58-amino acid insert near the N-terminus, showed minimal
      bundling activity. tau 4-induced bundling could be inhibited by the addition of
      0.5 M NaCl or 0.4 mM estramustine phosphate, conditions which are known to
      inhibit tau binding to microtubules. A tau construct that contained only the
      microtubule binding domains plus 19 amino acids to the C-terminus was fully
      capable of bundling microtubules. Phosphorylation of tau 3 with cAMP-dependent
      protein kinase had no effect on its ability to induce microtubule bundling. These
      results indicate that tau protein is directly capable of bundling microtubules in
      vitro, and suggests that different tau isoforms differ in their ability to bundle
      microtubule filaments.

PMID- 1360543
TI  - Identification of mouse type-2-like astrocytes: demonstration of glutamate and
      GABA transmitter activated responses.
AB  - We have identified mouse type-2-like astrocytes and examined some of their
      electrophysiological properties. Cultures were prepared from P4 mouse neopallia.
      We demonstrate that mouse type-2-like astrocytes can be identified using the
      following criteria: presence of glial fibrillary acidic protein (GFAP), presence
      of chondroitin sulfate polysaccharide, and presence of gamma-aminobutyric acid
      (GABA). A2B5-binding is not a sufficient criterion to identify O2A lineage cells
      in mouse neopallial glial cultures since the monoclonal antibody A2B5 binds not
      only to O2A lineage cells but also to a subpopulation of large, flat type-1-like
      astrocytes. Mouse type-2-like astrocytes have resting membrane potentials of 
      76.2 +/- 2.1 mV-i.e., similar to that of mouse type-1-like astrocytes. The input
      resistance of 44.2 +/- 0.5 M omega is an order of magnitude greater than that of
      type-1-like astrocytes suggesting the type-2-like astrocytes are not extensively
      electrically coupled either to each other or to type-1-like astrocytes. Glutamate
      application caused an 8.8 +/- 1.7 mV depolarization of type-2-like astrocytes.
      Application of glutamate to barium treated astrocytes caused a fast
      depolarization with a peak amplitude of 21.4 +/- 1.8 mV; the cells repolarized
      from this peak by about 10 mV and upon removal of glutamate returned to its pre
      glutamate value. Application of GABA caused a transient depolarization of 14.0 +/
      1.7 mV. The presence of barium resulted in a steady-state GABA-induced
      depolarization of 10.3 +/- 2.0 mV. Neither SITS nor beta-alanine interfered with
      the amplitude of the glutamate and GABA responses.

PMID- 1360544
TI  - S-100 beta and insulin-like growth factor-II differentially regulate growth of
      developing serotonin and dopamine neurons in vitro.
AB  - To study the phenotypic specificity of S-100 beta and insulin-like growth factor
      II (IGF-II) for developing monoamine neurons, serotonin (5-HT) neurons from the
      embryonic day 14 (E14) rostral raphe or dopamine (TH) neurons from the substantia
      nigra/ventral tegmental area were cultured for 3 days in vitro (3 DIV) in the
      presence of these factors. Neuronotrophic effects were analyzed by computer
      assisted morphometry of 5-HT and TH-immunoreactive neurons. S-100 beta and IGF-II
      differentially regulated the growth of 5-HT and TH neurons but did not affect
      their survival. S-100 beta significantly increased several parameters of neurite
      outgrowth by 5-HT neurons but inhibited the spatial extent (field area) of TH
      neurites. IGF-II promoted growth of cell bodies of both phenotype, but only
      stimulated neurite outgrowth by TH neurons. S-100 beta and IGF-II differentially
      affected the number of GFAP immunoreactive cells from raphe and substantia nigra,
      but these effects did not correlate with the specificity of neuronotrophic
      effects. S-100 beta and IGF-II immunoreactivities were expressed in glial
      cultures derived from the same brain regions, raising the possibility that these
      factors have autocrine effects on glia as well as paracrine actions on neurons.
      The results of this study suggest that specificity of neurotrophic factors for
      particular embryonic neurons may be correlated with their neurotransmitter
      phenotype.

PMID- 1360545
TI  - Recombinant human ciliary neurotrophic factor alters the threshold of hippocampal
      pyramidal neuron sensitivity to excitotoxin damage: synergistic effects of
      monosialogangliosides.
AB  - Ciliary neurotrophic factor (CNTF) is a multifunctional protein which not only
      promotes neuronal survival in vitro and in vivo but also controls cell division
      of neuronal precursors, transmitter differentiation, and glial cell
      differentiation. Recent studies have indicated that neurotrophic factors can
      alter hippocampal neuronal threshold to excitotoxin sensitivity. To examine such
      a role for CNTF, cultures of rat embryonic hippocampal neurons were maintained
      with recombinant human CNTF for different times, prior to exposure to a toxic
      dose of glutamate at 5 days in vitro for a further 24 hr. The cytotoxic action of
      200 microM glutamate (approximately 40% of pyramidal neurons remaining after 24
      hr) was reduced in a concentration-dependent manner in cultures receiving a prior
      exposure to CNTF within the first 3 days of cell plating: 30 ng/ml CNTF permitted
      about 75% of the initial number of pyramidal neurons to survive. Presentation of
      CNTF less than 48 hr before glutamate challenge was ineffective at up to 100
      ng/ml. When pyramidal neurons were cultured with a subthreshold concentration (2
      ng/ml) of CNTF together with 10 microM of the monosialoganglioside GM1 (or its
      inner ester form) in the same paradigm, the resulting neuronal survival was
      similar to that seen with 30 ng/ml CNTF in the face of a glutamate challenge.
      Such low doses of either CNTF or ganglioside alone were ineffective. The ability
      of trophic factors to influence the threshold of neuronal sensitivity to
      excitatory amino acid injury suggests that these proteins could play an important
      role in the reparative capacity of acutely traumatized central neurons and in
      neurodegenerative diseases linked to an excitotoxic mechanism.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1360546
TI  - Effect of acute trauma on the levels of intracellular cAMP, cGMP and DNA: studies
      on endocrinology and metabolism.
AB  - In this experiment, we used morgrel dogs to study the effect of trauma on the
      neuro-endocrine and metabolic organs and the effects of hormones on metabolism by
      determining the levels of intracellular cAMP, cGMP and DNA. From the changes in
      intracellular nucleotides, we learned that many neuro-endocrine organs and the
      main metabolic organs are characteristic of predominance in alpha-adrenoreceptor
      after trauma, thereby leading to high blood sugar.

PMID- 1360547
TI  - Benzodiazepine prescription regulations.

PMID- 1360548
TI  - The effect of alpha 1-blocker, bunazosin on a murine model of congestive heart
      failure induced by viral myocarditis.
AB  - The purpose of this study was to investigate the therapeutic effect of an alpha 1
      blocker, bunazosin, using an experimental murine model of congestive heart
      failure induced by viral myocarditis. This model is characterized by a high
      incidence of severe myocarditis and subsequent congestive heart failure, and is
      suitable for the evaluation of the effect of drugs. To estimate myocardial damage
      objectively and quantitatively, we used antimyosin monoclonal antibody in
      addition to histopathological grading. Four-week-old BALB/c mice were inoculated
      with encephalomyocarditis virus. The mice were injected daily with bunazosin or
      saline as a placebo from the day of viral inoculation until day 7 (protocol-I) or
      day 14 (protocol-II), or from day 4 to day 14 (protocol-III). They were then
      injected with 1.5 microCi of indium-111 labeled antimyosin antibody and were
      killed 24 h later. The antimyosin cardiac uptake was counted and
      histopathological grading was performed. The heart-weight to body-weight ratio,
      left ventricular dimension, histopathological grades and antimyosin cardiac
      uptake were significantly lower in the bunazosin group than in the placebo group
      in protocol-II, but not in protocol-I or protocol-III. Bunazosin showed a
      protective effect against viral myocarditis only when it was started early after
      infection and continued until the stage of congestive heart failure.

PMID- 1360549
TI  - [The assessment of clinical usefulness of 131I-MIBG scintigraphy for localization
      of tumors of sympathetic and adrenomedullary origin--a report of multicenter
      phase III clinical trials].
AB  - A phase III clinical study of 131I-metaiodobenzylguanidine (131I-MIBG) was
      performed in 66 patients with tumors of sympathetic and adrenomedullary origin,
      including 32 patients with suspected pheochromocytoma, 25 with suspected
      neuroblastoma, 7 pre- or postoperative medullary carcinoma of the thyroid and
      each with carcinoid and suspected Sipple's syndrome. A total of 150 sites which
      were confirmed for presence (72 sites) or absence (78 sites) of tumors were
      examined on 131I-MIBG scintigrams. True positive ratio of the scintigraphy was
      84.7% (61/72) and true negative ratio was 94.9% (74/78). Positive scintigraphy
      was obtained in 86.5% (32/37) of pheochromocytoma, 78.6% (22/28) of neuroblastoma
      and 100% (6/6) of medullary carcinoma of the thyroid. Accumulation of 131I-MIBG
      was seen in 16.8% of normal adrenal glands. Neither adverse reactions nor
      abnormal laboratory findings were noted in relation to 131I-MIBG injections. Our
      study indicates that 131I-MIBG is a safe and clinically useful radiotracers for
      the visualization and localization of tumors of sympathetic and adrenomedullary
      origin.

PMID- 1360550
TI  - [Radionuclide therapy of Sipple syndrome using iodine-131
      metaiodobenzylguanidine].
AB  - A 40-year-old female who had lung and liver metastases from malignant
      pheochromocytoma was treated with 3.7 GBq 131I-MIBG (metaiodobenzylguanidine).
      After the treatment, 131I-MIBG showed increased uptake in the metastatic lesions
      of the lung and liver. The size of tumor was no significant change on CT and MRI,
      but the intensity of liver metastases decreased gradually on MRI. Prior to the
      treatment, the levels of adrenaline and noradrenaline were high. One to three
      days after treatment, the level of these laboratory data further increased, but
      they gradually decreased in 1 to 3 months. These changes may be due to necrosis
      of tumor tissue.

PMID- 1360552
TI  - Analysis of complement C4 loci in Caucasoids and Japanese with idiopathic
      membranous nephropathy.
AB  - Deletion of the HLA class III complement gene, C4A, has been linked with
      susceptibility to a number of autoimmune diseases. In this study, we show a
      strong positive association between C4A gene deletion and development of
      idiopathic membranous nephropathy (IMN) in European Caucasoids [patients, 17/27
      (63%); healthy controls, 13/65 (20%); RR 6.8; P = 0.003]. To clarify whether C4A
      deletion is an independent risk factor for IMN or is increased secondarily to the
      Caucasoid HLA A1, B8, DR3 extended haplotype, we examined the frequency of C4A
      deletion in Japanese patients, in whom the disease is associated with another HLA
      haplotype (DR2-DQw1). Analysis of 31 Japanese patients and 46 healthy controls
      showed that C4A deletion was present in only one patient (3%) and one control
      (2%). In addition, examination of the C4B locus in Japanese patients showed that
      there was no significant increase in the estimated frequency of C4B deletion in
      patients against controls (31 vs. 27%) and no difference in the frequency of the
      C4B long gene (73 vs. 87%) or C4B short gene (77 vs. 78%). We conclude that
      although C4A deletion confers significant risk of IMN in Caucasoids, there is no
      significant association between C4 polymorphism, as detected here, and risk of
      IMN in Japanese. This suggests that either C4A deletion is irrelevant to the
      pathogenesis of IMN or that more than one genetic mechanism is involved.

PMID- 1360551
TI  - Autoreactive kidney-infiltrating T-cell clones in murine lupus nephritis.
AB  - T-cells have been implicated in autoimmune renal injury. To examine the role of T
      cells in lupus nephritis we propagated T-cell clones from the cortical
      interstitium of MRL/lpr mice. All isolated kidney-infiltrating (KI) T-cell clones
      [6] express surface markers identical to the T-cells regulated by the lpr gene
      (Thy 1.2+, TCR alpha/beta +, Lyt-2-, L3T4-, B220+). Although KI T-cell clones
      have the same surface markers as lymph node-infiltrating (LNI) T-cells, they
      differ functionally. KI T-cells, but not LNI T-cells, are autoreactive and kidney
      specific, exclusively proliferating to renal tubular epithelial (TEC) and
      mesangial cells. In addition, unlike LNI T-cell supernatants (SN), KI T-cell
      clones SN induce class II and ICAM-1 on cultured TEC. When KI T-cell clones are
      injected under the renal capsule, class II is increased on TEC. All clones
      transcribe mRNA for cytokines capable of inducing class II and ICAM-1 (IL-4, TNF
      alpha, IFN-gamma). Anti-IFN-gamma mAb prevents the induction of class II and ICAM
      1 on cultured TEC. Since class II and ICAM-1 expression on TEC precedes renal
      injury, the ability to propagate autoreactive, kidney-specific T-cell clones that
      induce these molecules provides evidence for their role in initiating renal
      injury in MRL/lpr mice.

PMID- 1360553
TI  - Analysis and isolation of renal tubular cells by flow cytometry.
AB  - The cells of the renal cortex have rich heterogeneity of structure and function.
      Flow cytometry, the technique of rapid laser-based single cell analysis, can give
      information about cellular mixtures not obtainable by any other means. We
      examined a variety of fluorescent markers to identify populations of renal cells
      by flow cytometry. Cellular digests of rat cortex were fluorescently stained with
      either enzymatic activity probes, or polyclonal antibodies. Fluorescent staining
      for the proximal marker gamma-glutamyl-transpeptidase (tau-GT) was an order of
      magnitude brighter than autofluorescence, and stained 71 +/- 11% of the cells.
      Second, we colocalized enzymatic and antibody markers. There was tight
      colocalization of tau-GT enzyme activity, detected with fluorogenic substrates,
      with specific surface binding of tau-GT antibodies. Third, populations of
      fluorescently labelled cells can be rapidly isolated by flow cytometry sorting.
      Flow cytometry sorting isolated 10(7) cells positive for the proximal tubular
      marker tau-GT in a little under one hour. The sorted cells were viable with 99 +/
      2% trypan blue exclusion (N = 8). Sodium-dependent phloridzin-inhibitable
      glucose uptake was present in sorted cells, with greater uptake/mg protein than
      in unsorted controls. The sorted cells grew in culture as a monolayer of tightly
      adherent cuboidal cells. Hence, flow cytometry allows us to quantitate the
      heterogeneity in mixed renal cellular digests. Flow cytometry allows us to
      rapidly isolate millions of cells according to fluorescently tagged markers. The
      isolated cells are viable, retain sodium-dependent transport properties, and grow
      in culture.

PMID- 1360555
TI  - [Narcotic analgesics. Part I. Pharmacokinetics of opiate receptors].

PMID- 1360554
TI  - Mesangial cell killing by leukocytes: role of leukocyte oxidants and proteolytic
      enzymes.
AB  - Mesangial cells from human and rat kidney were examined for sensitivity to
      killing by neutrophils. Cells from both species were sensitive to killing by
      phorbol myristate acetate-stimulated neutrophils. Catalase was highly protective
      while superoxide dismutase was less protective and a number of protease
      inhibitors were not protective. Strong protection was also observed with the iron
      chelators, deferoxamine and phenanthroline, and with the hydroxyl radical
      scavengers, dimethylthiourea and 5,5-dimethyl-1-pyrroline N-oxide. Pretreatment
      of the mesangial cells with deferoxamine followed by washing also provided
      protection. Mesangial cells were also killed by reagent hydrogen peroxide (H2O2)
      but were much less sensitive to injury by direct application of proteolytic
      enzymes. The ability of H2O2 to injure mesangial cells was prevented by pre
      incubation of the H2O2 with human leukocyte myeloperoxidase. These data suggest
      that killing is due primarily to the generation of H2O2 by the stimulated
      neutrophils and its further reduction in an iron-catalyzed reaction. The hydroxyl
      radical may be the reduction product that actually mediates lethal injury but
      lack of scavenger specificity prevents definitively concluding this. Mesangial
      cell killing by activated neutrophils could be significantly inhibited by
      monoclonal antibodies to CD11/CD18 molecules, suggesting that close contact
      between the target and effector cells is required for cytotoxicity. Although
      qualitatively similar to endothelial cells, the mesangial cells appeared to be
      quantitatively more oxidant sensitive than previously examined human and rat
      endothelial cells. Taken together, these data show that mesangial cells from rat
      and human are sensitive to leukocyte-induced injury and that injury results via
      an oxidant pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360556
TI  - Complete prevention of myocardial stunning, contracture, low-reflow, and edema
      after heart transplantation by blocking neutrophil adhesion molecules during
      reperfusion.
AB  - This study tested the hypothesis that preventing neutrophil adhesion during
      reperfusion, by blocking either the neutrophil membrane CD18 integrin complex or
      its endothelial and myocyte ligand, intercellular adhesion molecule-1 (ICAM-1),
      would reduce myocardial inflammation and edema and improve reflow and ventricular
      function after heart preservation and transplantation. After cardioplegia and
      insertion of a left ventricular balloon, rabbit hearts were heterotopically
      transplanted into recipient rabbits either immediately (immediate, n = 12) or
      after preservation in 4 degrees C saline (3 hours of ischemia, n = 33). Forty
      five minutes before reperfusion, recipients of preserved hearts received
      intravenous infusions of either saline (vehicle, n = 13), anti-CD18 monoclonal
      antibody (Mab) R15.7 (2 mg/kg) (anti-CD18, n = 10), or anti-ICAM-1 Mab R1.1 (2
      mg/kg) (anti-ICAM, n = 10). During 3 hours of reperfusion the slope of the peak
      systolic pressure-volume relation and its volume-axis intercept, the exponential
      elastic coefficient of the end-diastolic pressure-volume relation, the unstressed
      ventricular volume, and the time constant of the exponential left ventricular
      pressure decay after dP/dtmin were serially measured. Myocardial blood flow was
      measured with microspheres from which coronary vascular resistance was
      calculated. After explanation, the degree of myocardial inflammation, estimated
      by tissue neutrophil sequestration (myeloperoxidase assay) and myocardial water
      content were determined. Within each group no significant differences in
      measurements made at 1, 2, and 3 hours of reperfusion were noted. Compared with
      the immediate transplantation group, the vehicle group demonstrated a significant
      increase in myeloperoxidase activity (3380 +/- 456 versus 1712 +/- 552 microU/gm,
      p < 0.05), coronary vascular resistance (115.5 +/- 13.4 versus 70.5 +/- 10.6
      U/gm, p < 0.05), and myocardial water content (79.8% +/- 0.4% versus 75.6% +/-
      1.3%, p < 0.05), a significant decrease in unstressed ventricular volume (a
      leftward shift in the end-diastolic pressure-volume relation) (-0.49 +/- 0.24
      versus 0.28 +/- 0.21 ml, p < 0.05), and a marked prolongation in exponential left
      ventricular pressure delay after dP/dtmin (156.64 +/- 3.81 versus 37.25 +/- 3.34
      msec, p < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1360557
TI  - Double-blind trial of aspirin in primary prevention of myocardial infarction in
      patients with stable chronic angina pectoris. The Swedish Angina Pectoris Aspirin
      Trial (SAPAT) Group.
AB  - Clinical trials have demonstrated a prophylactic role for aspirin in myocardial
      infarction and in unstable angina pectoris. The Swedish Angina Pectoris Aspirin
      Trial (SAPAT) is the first prospective study of aspirin in stable angina. 2035
      patients were randomised double-blind to treatment with aspirin 75 mg daily or
      placebo. All patients were treated with sotalol for control of symptoms. The
      median duration of follow-up was 50 months. Compared with the placebo+sotalol
      group, the aspirin+sotalol group had a 34% (81 vs 124 patients) reduction in
      primary outcome events (myocardial infarction and sudden death; 95% confidence
      interval 24-49%; p = 0.003) and the reduction observed in secondary outcome
      events (vascular events, vascular death, all cause mortality, stroke) ranged from
      22% to 32%. Treatment withdrawal caused by adverse events occurred in 109
      patients in the aspirin+sotalol group and 100 in patients in the placebo+sotalol
      group; major bleeds, including haemorrhagic stroke, occurred in 20 and 13
      patients, respectively (not significant). The addition of a low dose of aspirin
      to sotalol treatment showed significant benefit in terms of cardiovascular
      events, including a significant reduction in the incidence of first myocardial
      infarction in patients with symptoms of stable angina pectoris.

PMID- 1360558
TI  - Effect of negative pressure ventilation in severe chronic obstructive pulmonary
      disease.
AB  - The hypothesis that patients with chronic obstructive pulmonary disease (COPD)
      have chronic inspiratory muscle fatigue was tested in an effectiveness trial in
      which negative pressure ventilation (NPV) was used to produce inspiratory muscle
      rest. In a double-blind study 184 patients with severe COPD were randomly
      allocated active or sham NPV treatment for a 12-week period of home use. The
      distance walked in a 6 min walk test was the primary outcome variable. Secondary
      outcome measures were cycle exercise endurance time, severity of dyspnoea,
      quality of life, arterial blood gas tensions, and respiratory muscle strength.
      The percentage reduction in amplitude of the diaphragmatic electromyographic
      signal multiplied by hours of NPV was used to reflect the dose of NPV so we could
      examine dose-response relations. Analysis was based on intention to treat. We
      found no evidence of a clinically or statistically significant difference in any
      outcome measure between active and sham groups. No dose-response relation was
      observed. Moreover, the intervention was poorly accepted despite substantial
      clinical support. We conclude that NPV as used in this study is difficult to
      apply and ineffective when used with the aim of resting the respiratory muscles
      in patients with stable COPD.

PMID- 1360559
TI  - Impaired endothelium-dependent vasodilation of forearm resistance vessels in
      hypercholesterolaemia.
AB  - Endothelium-dependent vasodilation in response to acetylcholine is impaired in
      the coronary microvasculature of hypercholesterolaemic subjects. Outside the
      coronary circulation, however, it has been suggested that hypercholesterolaemia
      results in a functional abnormality of vascular smooth muscle rather than in
      endothelial dysfunction. We examined vasodilator responses to acetylcholine,
      methacholine, and the endothelium-independent vasodilator sodium nitroprusside in
      the forearm resistance vessels of 12 men with primary hypercholesterolaemia and
      12 normocholesterolaemic male controls. Endothelium-dependent vasodilation in
      response to acetylcholine was impaired in hypercholesterolaemic patients compared
      with controls: at the highest dose of drug (15 micrograms per min) mean blood
      flow in the forearms of the hypercholesterolaemic group was only 52% (95% Cl 31
      88%) of that in the control group. Responses to sodium nitroprusside and to
      methacholine in the two study groups were not significantly different. These
      results indicate that endothelial dysfunction in hypercholesterolaemic subjects
      is generalised and extends to vascular beds outside the coronary circulation.
      Selective impairment to acetylcholine suggests that, at a molecular level, the
      defect is limited to a specific pathway.

PMID- 1360560
TI  - Polymerase chain reaction for diagnosis of meningococcal meningitis.
AB  - Meningococcal disease is normally suspected on clinical grounds but confirmed by
      isolation of Neisseria meningitidis from blood or cerebrospinal fluid (CSF), or
      by detection of gram-negative diplococci in CSF. After parenteral antibiotics are
      started the isolation rate of meningococci from blood cultures drops from 50% to
      less than 5% and the chances of CSF being positive by culture or microscopy are
      also reduced. We used the polymerase chain reaction (PCR) in a blinded study to
      detect meningococcal DNA in 54 CSF samples from patients with meningococcal
      disease or from controls. The PCR primers were specific for the meningococcal
      insertion sequence IS1106. The sensitivity and specificity of this PCR for
      diagnosis of meningococcal meningitis were both 91%. Sensitivity was not affected
      by prior antibiotic treatment. The IS1106 PCR is a rapid and sensitive test for
      confirmation of the diagnosis of meningococcal meningitis.

PMID- 1360561
TI  - Renal biopsy findings in hypertensive patients with proteinuria.
AB  - 27 patients with hypertension and persistent proteinuria were investigated by
      renal biopsy. The 13 patients without structural glomerular abnormalities were
      younger and had less proteinuria than the other 14, but otherwise the two groups
      had similar clinical features. 6 of the 14 had diffuse glomerular abnormalities;
      the other 8 had segmental sclerosing lesions, which were mainly in the hilum of
      the glomeruli, as seen in states of glomerular overload. Glomeruli in all groups
      were larger than those in normotensive people. It is possible that hypertension
      causes glomerular enlargement, proteinuria, and segmental glomerular lesions
      because of loss of functioning glomeruli due to ischaemia.

PMID- 1360563
TI  - Outcomes and PORTs.

PMID- 1360564
TI  - Negative-pressure ventilation for chronic obstructive pulmonary disease.

PMID- 1360565
TI  - Mapping sexual lifestyles.

PMID- 1360562
TI  - Molecular evaluation of residual disease as a predictor of relapse in acute
      promyelocytic leukaemia.
AB  - Acute promyelocytic leukaemia (APL) is characterised by a unique fusion
      transcript, PML/RAR alpha. We tested for this transcript in 35 APL patients who
      were in apparent remission after various treatments. 11 of 13 patients who tested
      positive 4 months after achieving remission were in relapse 1-4 months later. All
      22 patients who tested negative at 4 months were disease-free after a further 3
      months to five years. The test may therefore prove useful in determining the need
      for additional treatment during clinical remission.

PMID- 1360566
TI  - New gonadotropins for old?

PMID- 1360567
TI  - Second-hand bones?

PMID- 1360568
TI  - Pathophysiology of the irritable bowel syndrome.

PMID- 1360569
TI  - Clinical approaches to irritable bowel syndrome.

PMID- 1360570
TI  - Insulin resistance: an adaptation for weight maintenance.

PMID- 1360572
TI  - Change in course for health-insurance industry.

PMID- 1360571
TI  - John Bostock, hay fever, and the mechanism of allergy.

PMID- 1360573
TI  - USA: civil liberty and control of tuberculosis.

PMID- 1360574
TI  - Death of remand prisoner.

PMID- 1360575
TI  - Clotting factors and hepatitis A.

PMID- 1360576
TI  - Clotting factors and hepatitis A. Working Group on Hepatitis A and Clotting
      Factors.

PMID- 1360577
TI  - Clotting factors and hepatitis A.

PMID- 1360578
TI  - Augmented tumour necrosis factor in Reye's syndrome associated with dengue virus.

PMID- 1360579
TI  - HLA-DR4 genotype and insulin-processing in insulin autoimmune syndrome.

PMID- 1360580
TI  - Mesalazine versus olsalazine for prophylaxis of ulcerative colitis relapse.

PMID- 1360581
TI  - Treatment of high-altitude pulmonary oedema.

PMID- 1360582
TI  - False-positive cases in detection of testosterone doping.

PMID- 1360583
TI  - Detection of HIV-1 DNA sequences in pre-ejaculatory fluid.

PMID- 1360584
TI  - Pre-ejaculatory fluid as potential vector for sexual transmission of HIV-1.

PMID- 1360585
TI  - Plasma viral load in symptom-free women and vertical transmission of HIV-1.

PMID- 1360586
TI  - Monitoring of hormone replacement therapy.

PMID- 1360587
TI  - Vancomycin-resistant enterococci in a district general hospital.

PMID- 1360588
TI  - Borrelia burgdorferi and Shulman syndrome.

PMID- 1360589
TI  - Serum lysosomal enzyme abnormalities in galactosaemia.

PMID- 1360590
TI  - Novel phenylketonuria mutation detected by analysis of ectopically transcribed
      phenylalanine hydroxylase mRNA from lymphoblast.

PMID- 1360591
TI  - Ginkgo biloba.

PMID- 1360592
TI  - McCarthyism in East German universities.

PMID- 1360593
TI  - Teaching of anatomy.

PMID- 1360594
TI  - BCG vaccination in Spain.

PMID- 1360595
TI  - Euthanasia.

PMID- 1360596
TI  - Re-use of syringes.

PMID- 1360597
TI  - Euthanasia.

PMID- 1360598
TI  - International library exchange system.

PMID- 1360599
TI  - ACE inhibitors and LDL-apheresis with dextran sulphate adsorption.

PMID- 1360600
TI  - Occupational exposure to glutaraldehyde in tropical climates.

PMID- 1360601
TI  - Occupational asthma in radiographers.

PMID- 1360602
TI  - Prenatal influences and breast cancer.

PMID- 1360603
TI  - Prenatal influences and breast cancer.

PMID- 1360604
TI  - Antibiotic dose adjustment in renal insufficiency.

PMID- 1360605
TI  - Antibiotic dose adjustment in renal insufficiency.

PMID- 1360606
TI  - Antibiotic dose adjustment in renal insufficiency.

PMID- 1360607
TI  - Meningococcal meningitis or septicaemia: a plea for diagnostic clarity.

PMID- 1360608
TI  - How accurate is death certification of multiple system atrophy?

PMID- 1360609
TI  - Adult coronary artery disease secondary to childhood Kawasaki disease.

PMID- 1360610
TI  - Acute nicotine administration increases somatostatin content and binding in the
      rat hypothalamus.
AB  - Within 4 minutes a single, intravenous injection of nicotine (0.3 mg/Kg) induced
      increases in somatostatin-like immunoreactivity concentrations in the rat
      hypothalamus but not in the striatum. These changes were associated with a
      significant increase in the specific binding of somatostatin to putative receptor
      sites in hypothalamic membranes, while no significant changes were found in
      striatum. The enhancement of somatostatin binding resulted from a rapid increase
      in the number of available receptors rather than a change in receptor affinity.
      This effect appears to be mediated by nicotinic cholinergic receptors, because
      pretreatment with a centrally active nicotinic receptor antagonist, mecamylamine
      (5.0 mg/Kg i.v.), prevented the nicotine-induced changes in somatostatin content
      and binding in the hypothalamus. Mecamylamine alone had no observable effect on
      the hypothalamic somatostatinergic system. These results suggest that the rat
      hypothalamic somatostatinergic system can be regulated by nicotine-like
      acetylcholine receptors.

PMID- 1360613
TI  - Nucleotide sequences of the major subunits of F9 and F12 fimbriae of
      uropathogenic Escherichia coli.
AB  - An Eco RV-Cla I fragment containing the gene encoding the F9 fimbrial subunit of
      the human uropathogenic Escherichia coli strain C1018 and a PstI-PstI fragment
      containing the F12 fimbrial subunit gene of the dog uropathogenic strain 1442
      have been cloned and the nucleotide sequence of the fragments determined. The
      structural gene of the F9 fimbriae (FniA) codes for a protein of 165 amino acid
      residues with a signal peptide of 25 amino acids. The F12 fimbrial gene (FtwA)
      codes for a protein of 155 amino acids which is preceded by a single peptide of
      21 amino acids. The amino acid sequences of the FniA and FtwA proteins deduced
      from the nucleotide sequence were compared with sequences of other known P
      fimbrial subunit proteins. As expected, most differences between the various
      proteins were found in the hypervariable regions defined by van Die et al.
      (1987). The N-terminal sequence of the FtwA protein differs from the one
      published by Klemm et al. (1983). FtwA contains two deletions found in comparison
      to the other fimbrial subunits.

PMID- 1360611
TI  - Chronic clonidine treatment and its termination: effects on penile erection and
      ejaculation in the dog.
AB  - The effects of chronic administration (4 weeks) of the alpha-2 adrenoceptor
      agonist clonidine (CL) and its termination on penile erection and ejaculation
      were investigated in male dogs. Penile erection and ejaculation were elicited by
      manual penile stimulation (for 5 min). CL (10 micrograms/kg/hr, s.c.) was
      delivered via osmotic minipump (Alza, 2ML-4). 3 or 7 days after the minipump
      implantation, CL caused a significant decrease in the amount of ejaculate
      produced by the genital stimulation without affecting the erectile potency.
      Ejaculatory ability returned to pretreatment levels despite continued CL
      administration, becoming evident in tests 14 days after initiation of treatment.
      Further, chronic CL (23 days) antagonized the inhibitory effects of acute
      administration of CL (0.05 mg/kg, i.p.). These data indicate tolerance to
      continued delivery of low doses as well as to acute administration of a higher
      dose. In the acute drug experiments, the ejaculatory inhibition elicited by CL
      (0.05 mg/kg, i.p.) was completely antagonized by pretreatment with yohimbine
      (0.05 and 0.10 mg/kg, i.p.), an alpha-2 adrenoceptor antagonist, but not with
      naloxone (1.0 mg/kg, i.p.), an opioid receptor antagonist. Furthermore, DG-5128
      (1.0 and 2.0 mg/kg, i.p.), a selective alpha-2 adrenoceptor antagonist that
      poorly penetrates the blood-brain barrier, failed to antagonize the CL-induced
      ejaculatory inhibition. This study suggests that functional alterations in the
      central alpha-2 adrenoceptor mechanism may be related to the changes in the
      ejaculatory capacity during chronic treatment with CL.

PMID- 1360612
TI  - The effect of beta blocking drugs on lipid peroxidation in rat heart in vitro.
AB  - Beta-adrenergic receptor blocking drugs include a structurally related class of
      drugs that are employed clinically to treat a variety of cardiovascular
      disorders. Since these drugs exert additional nonspecific effects including
      membrane stabilization, representative samples including atenolol, dilevolol,
      labetalol, metoprolol and propranolol were studied to determine their influence
      on lipid peroxidation. Homogenates or liposomes of adult rat hearts were
      incubated in the presence of various concentrations of propranolol or equivalent
      concentrations of dilevolol, labetalol, metoprolol or atenolol. Lipid
      peroxidation was stimulated with 50 microM FeSO4, 5 microM t-butyl hydroperoxide
      (homogenates) or 0.2 mM citrate FeSO4 (liposomes) plus O2. Lipid peroxidation, as
      assessed by both the thiobarbituric acid reaction and chemiluminescence, was
      reduced in a dose-dependent manner as the propranolol concentration was increased
      from 1 to 10 mM. The five beta-adrenergic receptor blocking drugs reduced lipid
      peroxidation both in crude homogenates and in liposomes; their effectiveness was
      related to their lipophilicity. Dilevolol, propranolol, labetalol and metoprolol
      at a concentration of 20 mM reduced lipid peroxidation by 45%, 37%, 35% and 28%,
      respectively. The hydrophilic blocker atenolol was ineffective in reducing lipid
      peroxidation even at elevated concentrations. Lipophilic beta-blocking drugs
      apparently are capable of exerting an antioxidant effect in protecting membrane
      lipids against peroxidation.

PMID- 1360614
TI  - Effect of attachment factors (pili plus Opa) on Neisseria gonorrhoeae invasion of
      human fallopian tube tissue in vitro: quantitation by computerized image
      analysis.
AB  - Pili (P) and opacity-associated proteins (Opa) facilitate Neisseria gonorrhoeae
      attachment to human fallopian tube epithelium. Subsequent effects on invasion are
      unproven. Computerized image analysis was used to study the effects of attachment
      factors on invasion by comparing a P+Opa+ variant to a P-Opa- variant of strain
      R10 in the fallopian tube organ culture model. Gonococci in sections of infected
      fallopian tube tissue were identified with FITC-labelled monoclonal anti
      gonococcal antibodies. Nomarski DIC microscopy was used to establish anatomic
      boundaries that excluded extracellular gonococci from invasion measurements. The
      area of intracellular fluorescence served as an index of gonococcal invasion.
      With conservative criteria to exclude extracellular gonococci, the per cent of
      the intracellular area occupied by fluorescent P+Opa+ gonococci was 18% compared
      to 4.7% for the P-Opa- variant (P < 0.001). Data suggest that P+Opa+ organisms
      invaded deeper than P-Opa- microbes over the same time period (P = 0.029). Intra
      observer variation in invasion measurements was not significant (P > or = 0.85),
      and inter-observer correlation was high (correlation coefficient = 0.96).
      Computerized image analysis is a rapid, reliable means of quantifying gonococcal
      invasion of fallopian tube epithelium. We conclude that gonococcal attachment
      factors can facilitate events which enhance gonococcal invasion of fallopian tube
      epithelium.

PMID- 1360615
TI  - Morphological and cytoskeletal changes in epithelial cells occur immediately upon
      interaction with Salmonella typhimurium grown under low-oxygen conditions.
AB  - Salmonella typhimurium grown under oxygen-limiting conditions were found to enter
      into, elicit actin filament rearrangement in, and effect morphological changes
      upon HEp-2 cells within 15 min after infection. Video microscopy revealed that
      host cell morphological changes associated with entry began within 1 min of
      productive adherence. Polarized Caco-2 cell morphology was affected 40 s after
      infection with low-oxygen-grown S. typhimurium. Stationary-phase S. typhimurium
      did not elicit these phenomena within this time-period even when adherence was
      enhanced with the afimbial adhesin, AFA-I. Thus, environmental cues regulate S.
      typhimurium invasion factors, allowing for immediate entry into host cells.
      Additionally, actin filament rearrangement and morphological changes in the
      eukaryotic host cell are essential for entry and occur within minutes of
      infection.

PMID- 1360616
TI  - The subcellular distribution of nickel in Ni-sensitive and Ni-resistant strains
      of Saccharomyces cerevisiae.
AB  - Examination of the subcellular distribution of nickel in a Ni-resistant strain
      N08 of Saccharomyces cerevisiae showed that 70% of the nickel is distributed in
      the vascular fraction, which contains large amounts of histidine. The nickel
      taken up by cells grown in medium containing a high concentration of histidine
      was preferentially distributed to the vacuole. Arginine and lysine did not affect
      the intracellular distribution of Ni. In a Ni-sensitive strain 0605-S6, the
      distribution of nickel into the vacuole was lower than that observed in strain
      N08. Strain 0605-S6 exhibited no increase in the histidine content of the
      vacuolar fraction when grown in a Ni-supplemented medium. The Ni-resistant
      mechanism appears to involve the sequestration of nickel to the vacuole, and
      histidine could play an important role in the reduction of free nickel in the
      vacuole by the formation of histidine-nickel complexes.

PMID- 1360617
TI  - Alcohol and H2-receptor antagonists.

PMID- 1360618
TI  - Antivenom use in Australia. Premedication, adverse reactions and the use of venom
      detection kits.
AB  - OBJECTIVES: To analyse reports of antivenom use and sequelae in Australia from
      July 1 1989 to June 30 1990. The value of snake venom detection kits (VDKs) was
      also analysed. METHODS: Information was obtained from antivenom usage reports
      returned to the Commonwealth Serum Laboratories and from personal letters sent to
      those reporting doctors. Information on VDKs was obtained from antivenom usage
      reports or from questionnaires packaged with VDKs. RESULTS: Reported antivenoms
      used were: red-back spider, 258 cases; funnel-web spider, 3 cases; stonefish, 26
      cases; box jellyfish, 6 cases; snake, 91 cases. Immediate reactions followed
      administration of red-back spider antivenom in only two patients and snake
      antivenoms in four patients. Delayed reactions (serum sickness) followed use of
      red-back spider antivenom in three patients, stonefish antivenom in two, and
      snake antivenoms in three. No reaction was life-threatening. Premedication was
      used in the majority of red-back spider bites and in 66 of 86 snake bites. Oral
      corticosteroids were given prophylactically after some uses of snake antivenom to
      prevent serum sickness. VDKs were used in 181 cases of snake bite and were
      reported as being useful in selecting appropriate snake antivenom in 31% of cases
      of antivenom use. (Only 10 of these 181 were also reported on the antivenom usage
      report.) Appropriate first aid was given in 61% of cases. There were 50% fewer
      snake bites reported than 10 years ago. CONCLUSIONS: Antivenoms in Australia are
      well tolerated with few immediate or delayed reactions. The use of premedication
      and prophylactic oral corticosteroids for four to five days after antivenom
      administration may be responsible for this low reaction rate. VDK results help
      select the appropriate antivenom; however, in some cases positive results were
      obtained from urine samples from patients with no symptoms of envenomation.

PMID- 1360619
TI  - Mondor's disease of the breast resulting from jellyfish sting.
AB  - OBJECTIVE: To present two cases of Mondor's disease of the breast resulting from
      jellyfish stings in Western Australia. CLINICAL FEATURES: A 30-year-old Caucasian
      woman presented with a palpable thickened cord in her right breast. The
      straightness of the cord suggested a thrombosed lymphatic. A 50-year-old
      Caucasian woman presented with an obvious palpable cord extending most of the
      length of her left breast. Mammography demonstrated no abnormality. Both women
      reported having been stung by jellyfish a month earlier. INTERVENTION AND
      OUTCOME: As Mondor's disease is a benign, self-limiting disease, the patients
      were reassured and reviewed routinely. In each case, the condition settled
      spontaneously over a period of several weeks. CONCLUSION: Jellyfish stings should
      be recognised as an unusual variant of the numerous causes which have been
      described for Mondor's disease.

PMID- 1360620
TI  - Non-prescription use of bronchodilator aerosols.

PMID- 1360621
TI  - [Report on the I Congress of the Polish Society of Pediatric Neurologists
      (Olsztyn, October 17-19, 1991)].

PMID- 1360622
TI  - Histochemical evaluation of energy metabolism in rat glioma.
AB  - The key enzymes of oxidative phosphorylation and glycolysis were evaluated
      histochemically in rat-implanted C6 gliomas using spot densitometry. Hexokinase,
      the initial enzyme for the glycolysis pathway, was 40% higher within tumour than
      the contralateral cerebral cortex. A similar increase within tumours for 2
      deoxyglucose was observed by autoradiography. Glucose-6-phosphate dehydrogenase
      (G6PDH), which is the first enzyme in the pentose phosphate pathway, shunting
      glucose towards nucleic acid synthesis, was more than 300% higher in gliomas
      compared with the normal cortex. In contrast, enzymes in the energy producing
      tricarboxylic acid cycle (succinate-, isocitrate-, and malate-dehydrogenase) and
      in the electron-transport system (cytochrome c oxidase) were significantly
      reduced in tumour (58% less than the contralateral cortex). Lactate dehydrogenase
      activity, which converts pyruvate to lactate, was 50% higher within tumour.
      Significant reductions of enzymatic activities also occurred in non-neoplastic
      tissue in ipsilateral hemisphere, with larger tumours. Some enzymes showed
      heterogeneous activity within tumours, especially G6PDH. These results suggest
      that: (1) energy production is more dependent on lactate production than on
      oxidative phosphorylation in C6 glioma, and (2) a significant part of the
      increased glucose utilization in glioma cells is due to increased activity of the
      pentose phosphate shunt for increased DNA synthesis, and not energy production.

PMID- 1360624
TI  - Determination of the rate of cerebral oxygen consumption and regional cerebral
      blood flow by non-invasive 17O in vivo NMR spectroscopy and magnetic resonance
      imaging: Part 1. Theory and data analysis methods.
AB  - Theory and novel data analysis methods of 17O inhalation measurements are
      presented for the calculation of CMRO2, regional cerebral blood flow (rCBF), the
      reflow (R), the arterial venous difference (AVD) and the partition coefficient
      (lambda). Several of the methods proposed for the determination of CMRO2 do not
      require measurements of regional cerebral blood flow and H2(17)O arterial
      concentration. All methods of analysis are based on the Kety-Schmidt approach.

PMID- 1360623
TI  - Cryosurgery re-visited for the removal and destruction of brain, spinal and
      orbital tumours.
AB  - Advances in neuroimaging and cryosurgical techniques have prompted us to re
      evaluate the potential of cryosurgical techniques for the removal and the
      destruction of various neoplasms. We have used cryosurgical instrumentation to
      remove tumours in the brain, spine and orbit in 71 patients without
      complications. Cryosurgery was used to facilitate removal and extraction in 64
      and to destroy residual neoplasms when removal was incomplete in 7.
      Intraoperative real time ultrasonic imaging permitted precise delimitation of
      tumours from surrounding tissues and allowed monitoring during the production of
      cryosurgical lesions thus permitting heretofore unavailable visualization of the
      production of cryogenic lesions in the central nervous system. New cryosurgical
      instrumentation was used to produce lesions up to three times larger than similar
      sized probes previously available. Our results reconfirm that cryosurgery
      facilitates the removal of tumours in the brain, spinal cord and orbit, reduces
      blood loss in vascular tumours, and is effective in ablating residual neoplasms
      involving the superior sagittal sinus, torcula and parasagittal areas. A Doppler
      flowmeter proved useful for monitoring sagittal sinus blood flow during the
      production of cryosurgical ablation of residual tumour attached to the walls of
      the sagittal sinus. Recent advances in ultrasonic and neuroimaging coupled with
      stereotactic techniques and improvements in cryosurgical instrumentation may
      prove useful in the future percutaneous destruction of selective intracranial
      neoplasms.

PMID- 1360625
TI  - Pathology of spinal cord lesions caused by ossification of the posterior
      longitudinal ligament, with special reference to reversibility of the spinal cord
      lesion.
AB  - This report describes pathological findings of the spinal cord damage, with
      ossification of the posterior longitudinal ligament (OPLL), with special
      reference to reversibility of such lesions. Twenty-five autopsy cases associated
      with OPLL were examined, and the spinal cord damage was pathologically classified
      into four categories based on degree of destruction (stage 0-3). In stage 0 and
      stage 1, major pathological changes in the gray matter and the degree of
      compression on the spinal cord were well correlated to deformity of the anterior
      horn. In stage 2 and stage 3, neurons were almost completely obliterated and
      necrosis with cavitation were frequently observed. Destruction of the spinal cord
      in stage 2 and stage 3 is considered to be irreversible; therefore, surgical
      treatment is recommended at stage 0 or stage 1.

PMID- 1360626
TI  - Plasma lipoproteins in cortical versus lacunar infarction with or without cardiac
      arrhythmia, and in transient ischaemic attacks: a case control study.
AB  - We investigated the relation of plasma lipids to the risk for cortical infarction
      with (22 cases) or without (38 cases) cardiac arrhythmias, for lacunar infarction
      (28 cases) and transient ischaemic attacks (TAI) (15 cases). In the group of
      cortical infarction with or without cardiac arrhythmias, we observed a maximum
      increase of total cholesterol, of very low density lipoprotein (VLDL) and low
      density lipoprotein (LDL), triglycerides, total Apolipoprotein (Apo) B, LDL-Apo B
      and Apo-A1. On the contrary, we observed a decrease of total ApoE, HDL-ApoE, a
      distribution of LDL in a single layer and the presence of LDL of small weight.
      TAI is different from the former group by a low level of HDL and the lack of
      abnormalities of Apo-A1, and on the distribution and the weight of LDL. Finally,
      lacunar infarction presents a normal plasma lipoprotein profile. These data
      suggest that previously demonstrated differences in LDL-cholesterol levels
      between patients with ischaemic stroke and control subjects may apply to patients
      with cortical but not lacunar infarction. The presence or not of a cardiac
      arrhythmia doesn't give a special lipoprotein profile, and TAI has no changes on
      the distribution and the weight of LDL. Therefore, separation of ischaemic
      strokes into types based on mechanism as large vessel atherosclerosis versus
      small vessel atherosclerosis may help clarify lipid-related risk factors in
      cerebrovascular disease.

PMID- 1360627
TI  - Change of xanthine dehydrogenase and xanthine oxidase activities in rat brain
      following complete ischaemia.
AB  - We studied the activities of xanthine dehydrogenase and xanthine oxidase in rat
      forebrain after complete ischaemia. Complete ischaemia was induced by
      decapitation after transcardiac infusion with saline. The activities of xanthine
      dehydrogenase and xanthine oxidase immediately after ischaemia were 93.3 +/- 38.7
      and 18.8 +/- 7.7 microU/mg protein, respectively, and at 24 h after ischaemia
      were 183.5 +/- 75.1 and 60.8 +/- 15.2 microU/mg protein, respectively. The ratios
      of xanthine dehydrogenase/xanthine oxidase immediately and 24 h after ischaemia
      were 5.04 +/- 1.03 and 3.04 +/- 0.99, respectively. These data indicate that
      xanthine dehydrogenase and xanthine oxidase activities were maintained even 24 h
      after complete ischaemia. Conversion of xanthine dehydrogenase to xanthine
      oxidase proceeds slowly during complete ischaemia.

PMID- 1360628
TI  - Can somatosensory evoked potential monitoring predict energy dynamics during
      controlled hypotension?
AB  - Somatosensory evoked potentials and redox (reduction/oxidation ratio) of
      cytochrome a,a3 were studied simultaneously before, during, and after controlled
      hypotension used for arteriovenous malformation resection. These studies were
      also conducted before and after ED-IC (external-internal carotid) bypass
      procedures for treatment of patients with transient ischaemic attacks. The former
      served as an acute model and the latter as a chronic model of low blood flow
      (ischaemia). The use of non-invasive reflection spectrophotometry (for redox
      studies) in conjunction with somatosensory evoked potentials (SSEP) has
      demonstrated that metabolic and electrophysiological changes parallel each other
      during "controlled" hypotension. The authors conclude that an analysis of SSEP
      changes are valuable in the study of metabolic and functional states of the brain
      during controlled hypotension.

PMID- 1360629
TI  - DNA synthesis and intracellular calcium elevation in porcine cerebral arterial
      smooth muscle cells by cerebrospinal fluid from patients with subarachnoid
      haemorrhage.
AB  - To understand the molecular mechanism of the pathogenesis of cerebral vasospasm
      following subarachnoid haemorrhage, we analysed the effect of cerebrospinal fluid
      from patients with subarachnoid haemorrhage on DNA synthesis and cytosolic-free
      calcium elevation in cultured porcine cerebral smooth muscle cells. Cerebrospinal
      fluid from patients on day 2 after subarachnoid haemorrhage induced transient
      elevation in cytosolic-free calcium levels. In contrast, the maximal elevation of
      cytosolic-free calcium levels induced by cerebrospinal fluid from control
      patients (without subarachnoid haemorrhage) was significantly lower than that
      induced by cerebrospinal fluid from patients with subarachnoid haemorrhage. In
      cultured porcine cerebral arterial smooth muscle cells, cerebrospinal fluid from
      patients with subarachnoid haemorrhage promoted levels of [3H]-thymidine
      incorporation (DNA synthesis) more than 2.5-fold higher than that promoted by
      cerebrospinal fluid from control patients without subarachnoid haemorrhage.
      However, in cultured aortic smooth muscle cells, there was no significant
      difference in [3H]-thymidine incorporation between cerebrospinal fluid from
      patients with subarachnoid haemorrhage and that by control cerebrospinal fluid.
      From these results in cerebral arterial smooth muscle cells, cerebrospinal fluid
      from patients following subarachnoid haemorrhage may play not only constrictive
      functions, evidenced by cytosolic-free calcium elevations, but also proliferative
      functions, demonstrated by promotion of [3H]-thymidine incorporation. The
      relevance of these factors to vasospasm will be discussed.

PMID- 1360630
TI  - Correction of ischaemic brain acidosis with SQ29,548/1-benzylimidazole.
AB  - Thromboxane A2 (TXA2) is a proaggregatory vasoconstrictor that is synthesized and
      released during reperfusion of ischaemic brain. We administered a TXA2 receptor
      antagonist, SQ29,548, and a thromboxane A synthase inhibitor, 1-benzylimidazole
      (1-BI), to rats subjected to 30 min of reversible forebrain ischaemia. Cerebral
      thromboxane B2 (TXB2), the stable metabolite of TXA2, measured after 60 min of
      reperfusion was 0.37 +/- 0.08 ng/mg brain protein in animals treated with
      SQ29,548/1-BI compared with 1.20 +/- 0.16 in ischaemic controls (p < 0.05).
      Cerebral pH determined by 31P magnetic resonance spectroscopy was higher in
      treated animals, 7.06 +/- 0.04, than in ischaemic controls, 6.5 +/- 0.01, after
      20 min of reperfusion (p < or = 0.01). The significant elevation of cerebral pH
      in treated animals persisted at 30 (7.17 +/- 0.05 vs. 6.5 +/- 0.01; p < or =
      0.01), 35 (7.17 +/- 0.05 vs. 6.44 +/- 0.04; p < or = 0.01), and 40 min of
      reperfusion (7.06 +/- 0.06 vs. 6.37 +/- 0.01; p < or = 0.05). We conclude that
      SQ29,548/1-BI reduces thromboxane levels and promotes resolution of tissue
      acidosis in ischaemic brain. The combination of a TXA2 receptor antagonist with a
      thromboxane A synthase inhibitor deserves further study as a potential treatment
      for acute cerebral infarction.

PMID- 1360631
TI  - Cholinergic deafferentation prevents delayed neuronal death of the hippocampal
      CA1 pyramidal neurons after transient forebrain ischaemia.
AB  - The relation between CA1 neurons, fimbria-fornix and cholinergic neurons of the
      basal forebrain was examined with the aid of Acetylcholine esterase (AChE)
      staining, Woelcke's staining and immunohistochemistry of Choline-acetyl
      transferase (ChAT). The transected side of the hippocampus was poorly stained by
      AChE two weeks after the transection, when the ipsilateral medial septum ChAT
      positive neurons were reduced, but showed good recovery with AChE six weeks
      later. Nerve growth factor (NGF) was added at a dose of 10 micrograms/100
      microliters immediately after the aspiration, and after that once per week with
      cisternal puncture. As a result, ipsilateral medial septum ChAT-positive neurons
      were preserved, but cross innervation with relation to hypertrophy of the
      cholinergic neurons was not detectable even six weeks after the transection.
      Furthermore, delayed CA1 neuronal death on the transected side of the hippocampus
      following occlusion of four vessels for 30 minutes was not detectable two weeks
      after the operation, although neuronal density was reduced after six weeks. The
      density of neurons on the transected side of the hippocampus in the CA1 subfield
      with treated NGF had not decreased significantly six weeks later. Therefore, we
      suspect that the input from cholinergic fibres must be transported to the
      hippocampal pyramidal neurons responding to NGF, and it was confirmed that
      cholinergic deafferentation prevents the delayed neuronal death of CA1 pyramidal
      neurons during transient ischaemia.

PMID- 1360632
TI  - Cranio-nasal median splitting for radical resection of craniopharyngioma.
AB  - A new surgical approach for radical resection of craniopharyngioma is presented.
      This approach (cranio-nasal median splitting) involves craniotomy in the centre
      of the frontal bone, removal of the median portion of the supraorbital bar that
      incorporates the nasal bone, and detachment of the medial canthal ligaments. The
      frontal lobes, the cribriform plates, the planum sphenoidale, and the upper nasal
      cavities are split in the midline. The extraventricular surface of the
      hypothalamus, the pituitary stalk, and the posterior portion of the Willis'
      arterial ring are well visualized through the midline infrachiasmatic route. The
      intraventricular surface of the hypothalamus is also visible in the same
      operative field through the lamina terminalis and/or the anterior portion of the
      corpus callosum. This excellent visualization is quite helpful for minimizing
      operative injury to the hypothalamus and the pituitary stalk whichever surface of
      the third ventricular floor the tumour is situated upon. Three cases of
      craniopharyngioma operated upon by this approach are presented. Discussions are
      focused not only on the indication, but on the advantages and disadvantages of
      this approach. The surgical techniques for reconstruction of the cranial base are
      also described, together with some precautions that should be taken to prevent
      possible postoperative complications.

PMID- 1360633
TI  - Changes of cerebral haemodynamics during rebleeding subsequent to subarachnoid
      haemorrhage with vasospasm.
AB  - A 40-year old patient with spontaneous subarachnoid haemorrhage and vasospasm in
      whom an acute rebleeding occurred during transcranial Doppler ultrasonography
      monitoring is reported. The Doppler recordings of the middle cerebral artery
      displayed an extreme modification in their configuration in the form of an
      orthograde systolic flow component with zero diastolic flow or an oscillating
      flow immediately after occurrence of rebleeding. Reoccurrence of a diastolic flow
      component in still markedly raised cerebrovascular resistance index could be
      demonstrated a short time later. Rebleeding in subarachnoid haemorrhage with
      preexisting vasospasm leads to a severe temporary disturbance of cerebral
      perfusion. The vasospasm is likely to lead to a delayed normalization of
      perfusion and thus to prolonged ischaemia.

PMID- 1360634
TI  - Creutzfeldt-Jakob disease.

PMID- 1360635
TI  - Modulation of cholecystokinin (CCK) gene-expression in a human neuroblastoma cell
      line: effects of serum on enhanced CCK and c-fos mRNA expression.
AB  - The effect of fetal-calf serum (FCS) and Forskolin (FKN) on cholecystokinin (CCK)
      and proto-oncogene c-fos mRNA expression in the human neuroblastoma cell line SK
      N-MC, cultured in serum free medium was studied by Northern blot analysis and
      nuclear run-off transcription analysis. Addition of FCS or FKN gradually
      increased the basal CCK mRNA level approximately four to six-fold after 2-4 h. In
      contrast, a strong and transient increase of the c-fos mRNA-level was observed,
      approximately forty to fifty-fold after 50-60 min over unstimulated cells.
      Nuclear run-off transcription analysis indicates that c-fos mRNA is
      constitutively expressed and transcription may be further stimulated by FCS and
      FKN. Moreover, in SK-N-MC nuclei, transcription of the c-fos gene clearly
      precedes stimulated CCK-mRNA expression. This suggests that FOS, which is known
      to form a AP-1 heterodimer transcription complex with the proto-oncogen product,
      Jun, may bind to the tentative AP-1 binding site, found within the human CCK
      promoter and thereby modulates basal and enhanced CCK-mRNA expression in SK-N-MC
      cells.

PMID- 1360636
TI  - Pre-synaptic dopaminergic control mechanisms for CCK-8 like immunoreactivity in
      the rat medial frontal cortex.
AB  - In order to study the control mechanism of cholecystokinin (CCK) contents of the
      rat brain mediated by pre-synaptic receptors in dopamine (DA) neurons, R(+) and
      S(-) compounds of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP), which are
      selective pre-synaptic dopaminergic agents, were administered in rats at low and
      high doses. CCK-8-like immunoreactivity (CCK-8 LI) was measured in the medial
      frontal cortex. In another experiment, a neurotoxin, N-methyl-D-aspartic acid
      (NMDA) was used to degenerate efferent CCK neurons and CCK interneurons of the
      medial frontal cortex, followed by an intraperitoneal administration of
      apomorphine hydrochloride (APO) to study the effect on CCK-8 LI via the pre
      synaptic DA receptor. According to the results of these experiments, CCK-8 LI was
      increased in the medial frontal cortex in response to the stimulation of pre
      synaptic DA receptor, suggesting a control of CCK-8 release, at least in part, by
      the pre-synaptic DA receptor.

PMID- 1360637
TI  - Endogenous glutamate stimulates release of alpha-melanocyte-stimulating hormone
      from the rat hypothalamus.
AB  - Release of alpha-melanocyte-stimulating hormone (alpha-MSH) and glutamic acid was
      quantified from superfused slices of rat hypothalamus. Application of L-glutamic
      acid 10(-4) M failed to evoke release of alpha-MSH but, in the presence of 10(-4)
      M dihydrokainic acid (DHK) an inhibitor of glutamate uptake systems, caused
      significant stimulation of release. DHK caused gradual and sustained increases in
      both alpha-MSH and glutamate release. That in alpha-MSH was blocked by 10(-4) M
      DL-2-amino-5-phosphopentanoic acid, a competitive N-methyl-D-aspartic acid (NMDA)
      type glutamate receptor antagonist. We conclude that hypothalamic glutamate is
      subject to rapid uptake through mechanisms blocked by DHK and that alpha-MSH
      release is stimulated by endogenous and exogenous glutamate through NMDA-type
      receptors.

PMID- 1360638
TI  - A method for comparing benzodiazepine pharmacodynamics in the human brain.

PMID- 1360639
TI  - A prospective study of the effect of the appropriateness of foot-shoe fit and
      training shoe type on the incidence of overuse injuries among infantry recruits.
AB  - In a prospective study of the effect of the appropriateness of foot-shoe fit and
      training shoe type on the incidence of overuse injuries among infantry recruits,
      it was found that three shoe widths for each shoe length size were necessary to
      adequately accommodate the recruit population's foot anatomy. Recruits
      compensated for the lack of available shoe widths by choosing larger shoe sizes.
      However, this compensation did not result in an increase in the incidence of
      overuse injuries. Recruits who trained in basketball shoes had a lower incidence
      of overuse injuries of the feet than recruits who trained in infantry boots (p =
      0.0001), but the overall incidence of overuse injuries was the same in both
      groups.

PMID- 1360640
TI  - Gonadotropin-releasing hormone (GnRH) cells of the terminal nerve as a model
      neuromodulator system.
AB  - Modulation of ionic channel properties by neurotransmitters and hormones is
      called neuromodulation and may be the basis for many long-lasting changes in
      animal behavior, e.g. changes in the arousal or motivational states. Gonadotropin
      releasing hormone (GnRH), originally identified as a hypophysiotropic hormone, is
      now believed to act also as a neuromodulator. From studies of electrical
      activities and morphology of terminal nerve cells (major source of GnRH) of a
      fish brain, a general hypothesis regarding modulator neurons is proposed;
      modulator neurons have endogenous oscillatory activities which vary according to
      the animal's hormonal or environmental conditions. These modulator neurons, in
      turn, regulate neuronal excitabilities in a wide variety of brain regions
      simultaneously via multiple axonal branches.

PMID- 1360641
TI  - Norepinephrine reverses N-methyl-D-aspartate-mediated inhibition of long-term
      potentiation in rat hippocampal slices.
AB  - Application of 1 microM N-methyl-D-aspartate (NMDA) either immediately before or
      following tetanic stimulation inhibits the induction of CA1 hippocampal long-term
      potentiation (LTP). We have examined the effect of trans-amino-1,3
      cyclopentanedicarboxylic acid (ACPD), norepinephrine and acetylcholine on this
      NMDA-mediated LTP inhibition using extracellular recordings from in vitro rat
      hippocampal slices. When NMDA is accompanied by 100 microM ACPD or 10 microM
      norepinephrine, the block of LTP is overcome. The norepinephrine effect is
      mimicked by phenylephrine and methoxamine and is blocked by phentolamine and
      prazosin suggesting the involvement of alpha 1-adrenergic receptors.

PMID- 1360642
TI  - Excitatory effect of adenosine on neurotransmission is due to increase of
      transmitter release in the hippocampal slices.
AB  - Adenosine has dose-dependent biphasic excitatory and inhibitory effects on
      neurotransmission in the hippocampus. The mechanism of the excitatory action is
      not known although that of the inhibitory action has been well analyzed. Here we
      report on the mechanism of excitatory action of adenosine, using hippocampal
      slices. Studies of intracellular recordings of CA3 pyramidal neurons showed that
      the amplitude of EPSP was dramatically enhanced by application of adenosine at
      low concentration (0.1 microM) without changing resting membrane potentials,
      membrane conductance or the threshold for spike generation by injecting current
      pulses. On the other hand, the presence of adenosine at a concentration of 0.1
      microM during electrical stimulation to the slices increased 1.7 times the
      release of glutamate, an excitatory neurotransmitter in the hippocampus. These
      results indicate that the excitatory action of adenosine at low doses is due to
      the increase of transmitter release.

PMID- 1360643
TI  - The involvement of muscarinic, beta-adrenergic and metabotropic glutamate
      receptors in long-term potentiation in the fimbria-CA3 pathway of the
      hippocampus.
AB  - Possible modulatory actions of endogenous neurotransmitters on long-term
      potentiation (LTP) were investigated in the fimbria-CA3 pathway of rat
      hippocampal slices. Bath application of atropine (10 microM), but neither timolol
      (10 microM) nor D,L-2-amino-3-phosphonopropionate (AP3, 100 microM),
      significantly attenuated LTP induced by 20 pulses of 50 Hz stimulation. When
      stronger stimulation (3 trains of 100 Hz, 100 pulses) was used for the induction
      of LTP, timolol significantly attenuated LTP, but atropine and AP3 did not. These
      results suggest that, under specified conditions, endogenous acetylcholine
      through muscarinic receptors, and noradrenaline through beta-adrenergic receptors
      may modulate the generation of LTP in the fimbria-CA3 pathway. Metabotropic
      glutamate receptors may be involved not in the generation of LTP but in low
      frequency synaptic transmission, since 300-1,000 microM AP3 greatly reduced, or
      abolished synaptic transmission in this pathway.

PMID- 1360644
TI  - [An enzyme study of purine nucleotide biosynthesis in the plerocercoids of
      cestodes in the fam. Ligulidae].
AB  - By means of spectrophotometric method there was determined the activity of three
      enzymes of biosynthesis of purine nucleotides: amino imidazole ribonucleotide
      carboxylase (AIR-carboxylase, EC 4.1.1.21), an enzyme of biosynthesis of purine
      nucleotides de novo in plerocercoids of Schistocephalus pungitii and Digramma
      interrupta; inosine monophosphate-dehydrogenase (IMPh-dehydrogenase, EC
      1.2.1.14), an enzyme of salvage path, and adenylosuccinate lyase (EC 4.3.2.2), an
      enzyme taking part both in biosynthesis de novo and salvage in plerocercoids of
      Schistocephalus pungitii. The activity of AIR-carboxylase was not determined.
      Specific activities of adenylosuccinate lyase and IMPh-dehydrogenase amount to
      (1.3 +/- 0.3) x 10(-3) and (1.2 +/- 0.4) x 10(-3) mumole/min.mg protein,
      respectively. The activity of the three enzymes was determined in the liver of
      ten-spined stickleback, a host of S. pungitii plerocercoids. The question of
      metabolic dependence of Ligulidae plerocercoids on hosts to provide for purine
      bases is discussed.

PMID- 1360646
TI  - The regulation of the murine Hox-2.5 gene expression during cell differentiation.
AB  - The mouse Hox-2.5 gene containing a Drosophila Antennapedia-type homeobox
      sequence is expressed in a spatially and temporally restricted manner during
      embryogenesis. We found that the mouse embryonal carcinoma cell line P19
      expresses Hox-2.5 during differentiation by the treatment with retinoic acid
      (RA). Expression of the Hox-2.5 gene was not detected in undifferentiated P19
      cells, but detected 72 hours after treatment with RA. In order to analyze this
      inductive response, we first identified the Hox-2.5 transcription initiation site
      and a possible promoter region. Subsequently, we prepared constructs containing
      various Hox-2.5 DNA fragments fused to a firefly luciferase reporter gene and
      transfected these into undifferentiated or differentiating P19 cells. These
      studies have demonstrated that a region -279 to +15 with respect to the
      transcription initiation site has a differentiation-responsive promoter activity.
      Deletion analysis suggests that the sequences responsible for this induction are
      located in several distinct domains within the 294 bp promoter region. Two of the
      possible differentiation-responsive elements were identified by analysis of DNA
      protein interactions, and in vivo competition assays lend support to the notion
      that these regions are involved in the differential expression of Hox-2.5
      promoter activity.

PMID- 1360647
TI  - Delta-type DNA polymerase characterized from Drosophila melanogaster embryos.
AB  - Genetic and biochemical evidence suggests there are at least three DNA
      polymerases required for replication in eukaryotic cells. However, Drosophila
      embryonic cells have a very short duration S phase which is regulated
      differently. To address the question of whether embryos utilize different DNA
      polymerases, we employed Mono Q anion exchange chromatography to resolve the DNA
      polymerase activities. Two types of DNA polymerase, DNA polymerase delta and DNA
      polymerase alpha, were distinguished by: 1. copurification of DNA primase or 3'
      5'exonuclease activities; 2. immunoblot analysis with alpha-specific polyclonal
      antisera; 3. sensitivity to aphidicolin and BuPdGTP; and 4. processivity
      measurements with and without Proliferating Cell Nuclear Antigen. These
      observations suggest that Drosophila embryos, similar to nonembryonic cells, have
      both alpha- and delta-type DNA polymerases.

PMID- 1360645
TI  - Identification of a novel vertebrate homeobox gene expressed in haematopoietic
      cells.
AB  - This paper describes the characterisation of a novel chicken homeobox gene, Prh,
      whose encoded homeodomain sequence differs significantly from those of other
      factors which have been described. As expected, a portion of the encoded protein,
      containing the homeodomain, is capable of sequence-specific DNA-binding. Outside
      the homeodomain, Prh, possesses an N-terminal region extremely rich in proline
      residues and a C-terminal acidic portion, either of which may function as
      transcription regulatory domains. Since, among the chicken tissues tested, its
      transcription is restricted to haematopoietic cells, lung and liver, it may
      function in tissue-specific patterns of gene regulation. Human and murine Prh
      homologues have also been identified; so it is likely that such genes are a
      general feature of vertebrate genomes.

PMID- 1360649
TI  - Sequence of a tRNA gene cluster from the hydrozoan Podocoryne carnea.

PMID- 1360648
TI  - Purification and characterization of NF-R1 that regulates the expression of the
      human multidrug resistance (MDR1) gene.
AB  - We have purified a protein, NF-R1, that specifically binds to two unrelated
      motifs--the ATTCAGTCA motif and the GC-box motif--on the MDR1 proximal promoter.
      Purified NF-R1 has been confirmed by southwestern blotting to be a 110-kDa
      protein. Methylation interference analysis revealed that the nucleotides were in
      close contact with purified NF-R1 on the ATTCAGTCA and GC-box motifs. The
      nucleotides were required for the binding of NF-R1, as seen by competition gel
      mobility shift assay using point mutated oligonucleotides. In a CAT expression
      assay using the corresponding point-mutated MDR1 promoter fused to a CAT gene,
      binding inhibition of NF-R1 to the promoter resulted in 2- to 3-fold increases of
      CAT activity, as compared to the intact promoter in Adriamycin-resistant K562
      cells. Thus NF-R1 has a relation to the negative regulation of the MDR1 gene
      transcription.

PMID- 1360650
TI  - HES-1, a novel homeobox gene expressed by murine embryonic stem cells, identifies
      a new class of homeobox genes.

PMID- 1360652
TI  - Medical therapy in Crohn's disease.
AB  - Traditionally, sulfasalazine and corticosteroids have been used to treat Crohn's
      disease. However, therapy has been expanded to include other drugs, and several
      newer agents show clinical promise. The authors discuss the therapeutic options
      now available and describe results of several drug trials. Despite the apparent
      benefits of newer therapies, caution must be used in choosing appropriate
      treatment.

PMID- 1360651
TI  - Ondansetron to prevent emesis following N-acetylcysteine for acetaminophen
      intoxication.
AB  - We present a 17-year-old girl who developed persistent vomiting following
      acetaminophen overdose. Because of the amount of drug ingested (300 mg/kg
      acetaminophen) and the four-hour postingestion level (256 micrograms/ml),
      administration of N-acetylcysteine (NAC) was indicated. Emesis occurred
      immediately following the first three doses of NAC despite administering the drug
      by continuous nasogastric drip over one hour. Prior to the next attempt,
      ondansetron (0.15 mg/kg) was administered intravenously as an antiemetic. Thirty
      minutes following ondansetron, NAC was tolerated without further emesis. Although
      several antiemetics may have prevented further emesis, we chose ondansetron
      since, as a serotonin antagonist, it does not cause extrapyramidal side effects
      or sedation. In patients with potentially toxic drug ingestions, these side
      effects may be confused with or mask the adverse effects of the ingested drug,
      thereby interfering with the ongoing evaluation of the patient. Although not
      previously administered for this indication, ondansetron has several advantages
      over other antiemetic agents in the setting of an acute drug ingestion.

PMID- 1360653
TI  - Medical treatment after myocardial infarction. Results of studies using various
      methods.
AB  - Patients who have had myocardial infarction and are at risk for continued
      problems may benefit from several treatment methods (table 1). Beta-adrenergic
      blockers reduce subsequent cardiovascular morbidity and mortality through their
      effect on the myocardial supply-demand balance. Administration of angiotensin
      converting enzyme inhibitors reduces morbidity and mortality rates in myocardial
      infarction survivors who have diminished left ventricular ejection fraction.
      Aspirin and other anticoagulants are beneficial through their antiplatelet
      effects. Cardiac rehabilitation methods and aggressive management of lipids
      levels are also useful.

PMID- 1360654
TI  - Allergic rhinitis and hayfever.

PMID- 1360655
TI  - Potential drug interactions in heart disease.

PMID- 1360656
TI  - Beta-adrenergic responsiveness of the gastrointestinal tract in diabetic rats.
AB  - Recently, decreased gastrointestinal beta-adrenergic responses in experimental
      diabetes have been demonstrated. Gastrointestinal responses to beta-adrenoceptor
      agonists are impaired in both insulin-dependent and non-insulin-dependent
      diabetic rat. Insulin treatment improves the impaired gastrointestinal beta
      adrenergic responsiveness of diabetic rats. The improvement seen with insulin
      treatment on beta-adrenergic responsiveness is closely related to protein
      biosynthesis. The decreased beta-adrenergic responses in diabetic rat
      gastrointestinal tract seem to result from a decrease in the number of beta
      adrenoceptors. It is most likely that the decreased gastrointestinal beta
      adrenergic responsiveness is related to an impairment in the turnover of beta
      adrenoceptors as a consequence of diabetes and that insulin has a beneficial
      effect on the impaired receptor turnover.

PMID- 1360657
TI  - Studies on the interaction between formoterol and salmeterol in guinea-pig
      trachea in vitro.
AB  - The actions of and interaction between formoterol and salmeterol were studied on
      guinea-pig trachea in vitro. Tracheal strip preparations were contracted by 1
      mumol/l carbachol giving a near maximal contraction. Salmeterol in concentrations
      from 0.1 to 3 mumol/l relaxed the tracheal smooth muscle by about 30 per cent of
      the maximum relaxation produced by theophylline. Formoterol caused a
      concentration-dependent and almost complete relaxation with a pD2 of 8.56. In the
      presence of salmeterol there was a rightward shift of the concentration-response
      curve for formoterol. The pA2 for salmeterol was estimated to 7.42. Similar
      experiments with isoprenaline indicated that salmeterol has a low affinity for
      beta 1-adrenoceptors. Formoterol and salmeterol both inhibited in a concentration
      dependent manner the contractions evoked by stimulation of the vagus nerve in a
      tracheal tube preparation. The degree of inhibition decreased with increasing
      stimulation frequency. Complete inhibition was attained with salmeterol, but not
      with formoterol, at the highest frequency employed (45 Hz). The inhibiting effect
      of 10 mumol/l salmeterol was not blocked by 10 mumol/l sotalol, a beta
      adrenoceptor antagonist. It is concluded that salmeterol, in comparison to
      formoterol, is a partial beta 2-adrenoceptor agonist and has, at high
      concentrations, an additional unspecific inhibitory action.

PMID- 1360658
TI  - Lack of effect of certain histamine H2-receptor blockers on the glucuronidation
      of 7-hydroxy-4-methylcoumarin by human liver microsomes.
AB  - Contrary to the general belief that cimetidine and ranitidine spare
      glucuronidation of drugs, some authors have indicated that both cimetidine and
      ranitidine could inhibit the glucuronidation of paracetamol (acetaminophen) by
      cultured rat hepatocytes. Thus, we tested the effect of three histamine H2
      receptor blockers (cimetidine, ranitidine and famotidine) on the glucuronidation
      of 7-hydroxy-4-methylcoumarin (7-OH-4-MC) by human liver microsomes. None of the
      drugs studied produced significant inhibition of the glucuronidation of 7-OH-4-MC
      when used at concentrations up to 1.5 mM. Thus, even the new H2-receptor blocker,
      famotidine, spares glucuronidation. These findings further support the previous
      reports which suggest that glucuronide conjugation in humans is spared by H2
      receptor blockers.

PMID- 1360660
TI  - [Omnia tempus habent--on the significance of time for pathoanatomic thinking].

PMID- 1360659
TI  - Myocardial ultrastructure in the isolated rabbit heart exposed to dopamine,
      dobutamine, isoprenaline, G-strofanthin, xamoterol and hypoxia.
AB  - The isolated spontaneously beating heart was used for comparing the effects of
      hypoxia and positive inotropic drugs on myocardial ultrastructure. Hypoxia gives
      a significant decrease in the volume fractions of mitochondrial cristae relative
      to the total mitochondrial volume (Vvmcristae) and a significant increase in the
      volume fraction of mitochondrial matrix relative to the total mitochondrial
      volume (Vvmmatrix), but changes in volume fractions of mitochondria
      (Vvmitochondria) and myofibrils (Vvmyofibrils) were absent. Significant changes
      in ultrastructure in hearts treated with dopamine (0.6 microM), dobutamine (90
      nM), G-strofanthin (0.25 microM), xamoterol (32 nM) and isoprenaline (0.15 microM
      or 15 nM) were absent. Furthermore, myocardial effects in the isolated rabbit
      heart without exposure to any treatment showed a significantly decrease in oxygen
      consumption after 90 min. and a significant decrease in frequency of contractions
      after 120 min. perfusion time, but no change in contractility was seen. We
      conclude that this experimental model is useful in studies of positive inotropic
      drugs.

PMID- 1360661
TI  - [Polymerase chain reaction (PCR) in microbiology. Value and practical
      applications].
AB  - The gene amplification reaction (PCR) developed in 1985 is a molecular biology
      instrument which is used to amplify genomic restriction fragment lengths of micro
      organisms found in biological samples. At the moment, its applications to direct
      microbiological diagnosis remain to be determined precisely, and its strict
      technique is awaiting standardization. However, it is a powerful tool for
      molecular typing used to follow up an antiviral therapy or to analyse
      retrospectively paraffin-embedded tissue banks in search of viral or bacterial
      nucleic acids.

PMID- 1360662
TI  - [Acute myopathy complicating prolonged curarization and corticoid therapy for
      status asthmaticus].

PMID- 1360663
TI  - Molecular cloning and functional expression of a brain-specific somatostatin
      receptor.
AB  - The PCR and conventional library screening were used to clone the brain-specific
      somatostatin receptor rSSTR-4 from a rat genomic library. The deduced amino acid
      sequence encodes a protein of 384 amino acids and displays structural and
      sequence homologies with members of the G protein-receptor superfamily. The amino
      acid sequence of rSSTR-4 is 60% and 48% identical to that of somatostatin
      receptors SSTR-1 and SSTR-2, respectively, two recently cloned subtypes.
      Competition curve analysis of the binding properties of the receptor transiently
      expressed in COS-1 cells revealed a higher apparent affinity for somatostatin 14
      than for somatostatin 28. In contrast, the somatostatin analogs SMS 201-995, IM 4
      28, and MK-678 failed to displace specific binding in transfected cells. These
      characteristics resemble the pharmacological binding properties of the previously
      described brain-specific somatostatin-receptor subtype. Examination of the tissue
      distribution of mRNA for rSSTR-4 revealed expression limited to various brain
      regions with highest levels in the cortex and hippocampus. Thus, based on the
      pharmacology and tissue localization of this receptor, we conclude that rSSTR-4
      represents a brain-specific somatostatin receptor.

PMID- 1360664
TI  - Isolation of transglutaminase-reactive sequences from complex biological systems:
      a prominent lysine donor sequence in bovine lens.
AB  - The transglutaminase (protein-glutamine: amine gamma-glutamyltransferase, EC
      2.3.2.13)-catalyzed cross-linking of proteins in biological systems can often be
      inhibited by inclusion of small primary amines or glutamine-containing peptides,
      which act as site-specific blockers of the relevant acceptor (i.e., glutamine)
      and donor (i.e., lysine) functionalities of the natural substrates. Compounds
      such as dansylcadaverine and dansyl-epsilon-aminocaproyl-Gln-Gln-Ile-Val are
      particularly useful in sorting out acceptor-donor relationships among lens
      crystallins. Apart from its fluorescent properties, the dansyl hapten offered
      special advantages as a "handle" for the rapid isolation of transglutaminase
      targets even in the complex system of lens cortical homogenate. The dansylated
      peptide was incorporated into bovine lens proteins under the influence of the
      Ca(2+)-activated intrinsic transglutaminase and, after digestion by
      endoproteinase Glu-C, the tracer-containing fragments were isolated by affinity
      chromatography on an anti-dansyl antibody column. The major fluorescent peak was
      isolated by HPLC and sequenced by Edman degradation, which yielded
      phenylthiohydantoin amino acid derivatives for the first 10 cycles, EKPAVTAAPK,
      and none for the next 2. The sequence, corresponding to residues 165-174 of alpha
      B-crystallin, unambiguously identifies the known carboxyl-terminal domain, EK
      PAVTAAPKK, as the prominent lysine-donating fragment in bovine lens.

PMID- 1360665
TI  - Enhancement of human immunodeficiency virus (HIV)-specific CD4+ and CD8+
      cytotoxic T-lymphocyte activities in HIV-infected asymptomatic patients given
      recombinant gp160 vaccine.
AB  - Twenty-six human immunodeficiency virus (HIV)-infected asymptomatic patients with
      CD4+ lymphocytes > 400 per mm3 were randomly allocated to a range of doses of
      recombinant gp160 or a control (recombinant hepatitis B vaccine) on a double
      blind basis. Each patient received an injection at 0, 4, 12, 24, 36, and 48
      weeks. Treatment assignments were decoded when all patients reached 28 weeks of
      the study period. HIV-1-specific CD4+ and CD8+ cytotoxic T lymphocyte (CTL)
      activities were assessed in vitro before vaccination and 2 weeks after each
      injection. There were significant increases in major histocompatibility complex
      restricted HIV-1 Env-specific CD4+ and CD8+ CTL activities in 18 of 21 gp160
      vaccinees. No control-injected patients showed a significant change. Neither
      gp160 nor control recipients showed significant changes in HIV-1 Gag- and Pol
      specific CTL activities. HIV-1 Env-specific CD4+ and CD8+ CTL precursor
      frequencies were also measured in three vaccinees before and at 24 weeks after
      vaccine was started. CTL precursor frequencies also increased in both CD4+ and
      CD8+ populations. This study shows that this gp160 vaccine is immunogenic in
      enhancing HIV-1 Env-specific cytotoxic T-cell-mediated immunity in HIV
      seropositive individuals.

PMID- 1360666
TI  - Toward a cytogenetically based physical map of the wheat genome.
AB  - Bread wheat (Triticum aestivum L. em Thell) is well suited for cytogenetic
      analysis because the genome, buffered by polyploidy, can tolerate structurally
      and numerically engineered chromosomes for analysis over infinite generations.
      This feature of polyploidy can be used in developing a high-resolution,
      cytogenetically based physical map of the wheat genome. We show that numerous
      deletions, observed in the progeny of a monosomic addition of a chromosome from
      Triticum cylindricum in wheat, result from single breakpoints and a concomitant
      loss of distal fragments. Breakages occurred in euchromatic and heterochromatic
      regions. Forty-one deletions for chromosomes 7A, 7B, and 7D, and a set of
      genetically mapped DNA probes, were used to construct physical maps.
      Recombination was low in proximal chromosomal regions and very high toward the
      distal ends. Deletion mapping was more efficient than genetic mapping in
      resolving the order of proximal loci. Despite variation in size and arm ratio,
      relative gene position was largely conserved among chromosomes 7A, 7B, and 7D and
      a consensus group 7 physical map was constructed. Several molecularly tagged
      chromosome regions (MTCRs) of approximately one to a few million base pairs were
      identified that may be resolved by long-range mapping of DNA fragments. Thus, a
      cytogenetically based physical map may be used to integrate chromosome and DNA
      based maps. The MTCRs may simplify strategies for cloning of agronomically useful
      genes despite the genetic complexity and the large genome size of wheat.

PMID- 1360667
TI  - Thymic depletion and peripheral activation of class I major histocompatibility
      complex-restricted T cells by soluble peptide in T-cell receptor transgenic mice.
AB  - Injection of mice transgenic for a class I major histocompatibility complex
      restricted T-cell receptor with a soluble peptide antigen from influenza virus
      nucleoprotein results in clonal depletion of double-positive immature thymocytes
      in the thymus and activation of mature T cells in the periphery, accompanied by a
      transient up-regulation of the T-cell receptor and CD3 and CD8 coreceptor
      molecules.

PMID- 1360668
TI  - Up-regulation of intercellular adhesion molecule 1 transcription by hepatitis B
      virus X protein.
AB  - Intercellular adhesion molecule 1 (ICAM-1), a counter-receptor for lymphocyte
      function-associated antigen 1 on T cells, is critically important to a wide
      variety of adhesion-dependent leukocyte functions, including antigen presentation
      and target cell lysis. ICAM-1 expression by hepatocytes is increased in areas of
      inflammation and necrosis during chronic hepatitis B. Whether induction of ICAM-1
      is due to the effect of inflammatory cytokines or involves a direct effect of the
      hepatitis B virus (HBV) remains unknown. In the present study, transfection of
      the HBV genome into human hepatoma cell lines resulted in enhanced expression of
      ICAM-1 protein and RNA in the absence of inflammation. Results of subgenomic
      transfections indicated that the HBV X protein (pX) induced ICAM-1 expression.
      Nuclear run-on assays showed that pX induced the ICAM-1 gene by increasing its
      rate of transcription. Although both pX and interferon gamma induced
      transcription of ICAM-1, addition of interferon gamma to cells expressing pX did
      not show an additive or synergistic effect. These results indicate that pX can
      directly regulate expression of ICAM-1 and may participate in the
      immunopathogenesis of HBV infection.

PMID- 1360669
TI  - Tat-responsive region RNA of human immunodeficiency virus type 1 stimulates
      protein synthesis in vivo and in vitro: relationship between structure and
      function.
AB  - The Tat-responsive region (TAR) sequence is present at the 5' end of human
      immunodeficiency virus 1 mRNAs and as a cytoplasmic form of 58-66 nucleotides.
      TAR RNA blocks the activation and autophosphorylation of the double-stranded RNA
      activated protein kinase in vitro. We show here that TAR RNA also prevents the
      double-stranded RNA-mediated inhibition of translation in a cell-free system.
      Mutagenic and structural analyses of TAR RNA indicate that a stem of at least 14
      base pairs is required for this activity, whereas the loop and bulge required for
      transactivation by Tat are dispensable. Truncation of the RNA to 68 nucleotides
      results in the loss of translational rescue ability, suggesting that the short
      cytoplasmic TAR RNA produced by viral transcription in vivo may not have the
      capability to suppress activation of the kinase. However, because longer TAR
      transcripts stimulate expression in a transient assay in vivo, the TAR structure
      at the 5' end of viral mRNAs could still exert this function in cis.

PMID- 1360670
TI  - Identification and genetic mapping of a homeobox gene to the 4p16.1 region of
      human chromosome 4.
AB  - A human craniofacial cDNA library was screened with a degenerate oligonucleotide
      probe based on the conserved third helix of homeobox genes. From this screening,
      we identified a homeobox gene, H6, which shared only 57-65% amino acid identity
      to previously reported homeodomains. H6 was physically mapped to the 4p16.1
      region by using somatic cell hybrids containing specific deletions of human
      chromosome 4. Linkage data from a single-stranded conformational polymorphism
      derived from the 3' untranslated region of the H6 cDNA placed this homeobox gene
      more than 20 centimorgans proximal of the previously mapped HOX7 gene on
      chromosome 4. Identity comparisons of the H6 homeodomain with previously reported
      homeodomains reveal the highest identities to be with the Nk class of homeobox
      genes in Drosophila melanogaster.

PMID- 1360671
TI  - Genomic polymorphism, recombination, and linkage disequilibrium in human major
      histocompatibility complex-encoded antigen-processing genes.
AB  - Recently, two subunits of a large cytosolic protease and two putative peptide
      transporter proteins were found to be encoded by genes within the class II region
      of the major histocompatibility complex (MHC). These genes have been suggested to
      be involved in the processing of antigenic proteins for presentation by MHC class
      I molecules. Because of the high degree of polymorphism in MHC genes, and
      previous evidence for both functional and polypeptide sequence polymorphism in
      the proteins encoded by the antigen-processing genes, we tested DNA from 27
      consanguineous human cell lines for genomic polymorphism by restriction fragment
      length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage
      disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a
      polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage
      disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of
      recombination, however, seems to occur in the center of the complex, between the
      TAP1 and TAP2 genes.

PMID- 1360673
TI  - Variation across species in the size of the nuclear genome supports the junk-DNA
      explanation for the C-value paradox.
AB  - The amount of DNA in the nuclear genome (the DNA C-value) of eukaryotes varies at
      least 80,000-fold across species, and yet bears little or no relation to
      organismic complexity or to the number of protein-coding genes. This phenomenon
      is known as the C-value paradox. One explanation for the C-value paradox
      attributes the size of the nuclear genome to 'junk' (typically non-coding)
      genetic elements that accumulate until the costs to the organism of replicating
      excess DNA select against it. Across species, organisms that develop at a slower
      rate should tolerate more junk DNA. Alternatively, junk DNA may function as a
      nucleo-skeleton to maintain the volume of the nucleus at a size proportional to
      the volume of the cytoplasm in the cell. Across species, the DNA C-value is
      predicted to vary with the nuclear and cytoplasmic volumes of cells. Previous
      studies have not been able to distinguish between the skeletal-DNA and junk-DNA
      explanations for the C-value paradox. We report a study of DNA content in 24
      salamander species which does. The size of the nuclear genome is correlated with
      developmental rate even after the effects of nuclear and cytoplasmic volume have
      been removed. However, genome size is not correlated with cytoplasmic volume
      after controlling for developmental rate. These results support the view that
      junk DNA accumulates in the nuclear genome until the costs of replicating it
      become too great, rather than that it functions as a nucleo-skeleton.

PMID- 1360672
TI  - CD8 T cells can protect against an intracellular bacterium in an interferon gamma
      independent fashion.
AB  - Specific T-cell immunity to Listeria monocytogenes is thought to occur through
      the action of lymphokines which activate phagocytes to ingest and kill
      microorganisms. Interferon gamma (IFN-gamma) has been shown to be an effective
      mediator of this type of macrophage activation in vivo and in vitro. The
      monoclonal antibody H22.1 efficiently neutralizes endogenous IFN-gamma,
      exacerbates disease in a mouse model of L. monocytogenes infection, and inhibits
      the in vivo protective activity of a Listeria antigen-specific CD4 T-cell line.
      In contrast, in vivo protection by Listeria-immune CD8 T cells is not inhibited
      by the neutralizing anti-IFN-gamma monoclonal antibody. These results suggest
      that CD8 T cells can protect against an intracellular pathogen in an IFN-gamma
      independent manner.

PMID- 1360675
TI  - Low-level visual processing of biological motion.
AB  - Biological motion displays depict a moving human figure by means of just a few
      isolated points of light attached to the major joints of the body. Naive
      observers readily interpret the moving pattern of dots as representing a human
      figure, despite the complete absence of form cues. This paper reports a series of
      experiments which investigated the visual processes underlying the phenomenon.
      Results suggest that (i) the effect relies upon responses in low-level motion
      detecting processes, which operate over short temporal and spatial intervals and
      respond to local modulations in image intensity; and (ii) the effect does not
      involve hierarchical visual analysis of motion components, nor does it require
      the presence of dots which move in rigid relation to each other. Instead,
      movements of the extremities are crucial. Data are inconsistent with current
      theoretical treatments.

PMID- 1360674
TI  - Supply of O2 regulates O2 demand during utilization of reserves of poly-beta
      hydroxybutyrate in N2-fixing soybean bacteroids.
AB  - A liquid reaction medium containing dissolved air and oxyleghaemoglobin, but no
      energy-yielding substrate, was supplied to bacteroids confined in a stirred flow
      reaction chamber. The relative oxygenation of the leghaemoglobin in the chamber
      was determined automatically by spectrophotometry of the effluent solution, and
      the concentrations of free, dissolved O2 ([O2]) and rates of O2 consumption were
      calculated. Dissolved CO2 and NH3 from N2 fixation were determined in fractions
      of the effluent solution. Bacteroids utilized endogenous reserves of poly-beta
      hydroxybutyrate (PHB), which were depleted by 9.2% during a typical 5 h-long
      experiment. Stepwise increases in flow rate (increasing supply of O2) initially
      produced a drop in O2 demand and resulted in a rise in [O2] and a decline in N2
      fixation. Subsequently, O2 demand rose (presumably because of increased
      mobilization of substrate from PHB) and [O2] declined to a low level. N2 fixation
      was fully restored, or even enhanced, within 15-20 min of establishment of a new,
      steady [O2]. This pattern of regulation by O2 supply was completely eliminated by
      adding low concentrations (20-50 microM) of oxidizable substrate (succinate,
      malate, ethanol) to the reaction medium. During endogenous activity, rates of CO2
      evolution were proportional to, but less than, rates of O2 consumption up to 5.4
      nmol O2 min-1 mg-1, above which CO2 evolution exceeded O2 consumption. These and
      other features of endogenous activity are discussed in relation to sustaining N2
      fixation by nodules in vivo.

PMID- 1360676
TI  - DNA fingerprinting: parentage studies in natural populations and the importance
      of linkage analysis.
AB  - It has been suggested that a full linkage analysis is a prerequisite for
      confident paternity testing, by using DNA fingerprinting, in natural populations.
      These fears are based on a confusion between linkage and linkage disequilibrium
      and a misplaced assumption that linkage between bands will necessarily reduce the
      effective number of paternal-specific bands. Several methods for detecting
      linkage without resorting to the analysis of large sibships are considered, for
      example, by analysing half-sibships, by band-association, and by altering the
      experimental conditions used. Even if linkage is present, the magnitude of its
      effects are unlikely to undermine the accuracy of the technique, given the
      average levels of variability being detected. We conclude that the effects of
      linkage are only likely to present a problem when sample sizes are very small or
      when closely related individuals are being tested together.

PMID- 1360677
TI  - Limited MHC polymorphism in the southern elephant seal: implications for MHC
      evolution and marine mammal population biology.
AB  - Genes of the major histocompatibility complex (MHC) are highly polymorphic in
      most terrestrial mammal populations so far studied. Exceptions to this are
      typically populations that lack genome-wide diversity. Here I show that two
      populations of the southern elephant seal (Mirounga leonina) have low DNA
      restriction fragment length polymorphism at MHC loci when compared with
      terrestrial mammals. Limited studies on MHC polymorphism in two cetacean species
      suggest this is a feature of marine mammal populations in general. MHC
      polymorphism is thought to be maintained by balancing selection, and several
      types of disease-based and reproductive-based mechanisms have been proposed. For
      the three marine mammal species examined, the low MHC polymorphism cannot be
      explained by low genome-wide diversity, or by any reproductive-based selection
      pressure. It can, however, be explained by diminished exposure to pathogenic
      selection pressure compared with terrestrial mammals. Reduced exposure to
      pathogens would also mean that marine mammal populations may be susceptible to
      occasional pathogen-induced mass mortalities.

PMID- 1360678
TI  - Cerebral visual motion blindness: transitory akinetopsia induced by transcranial
      magnetic stimulation of human area V5.
AB  - The perception of visual motion can be selectively and reversibly compromised by
      transcranial magnetic stimulation (TMS) of a small region of cortex, roughly 1 cm
      in diameter and corresponding in position to human area V5. The reversible
      inactivation of a small and specialized visual area which receives its
      predominant input from area V1 and sends a powerful return (re-entrant) input
      back to it allowed us to study for the first time the backward influence of area
      V5 on area V1. In contrast to the complete and temporary visual motion blindness
      which occurs during stimulation of V5, a less-prominent interference with the
      perception of visual motion occurs at 70-80 ms after the onset of the visual
      stimulus when TMS is applied to V1. Because V5 is critical for the perception of
      coherent motion, and because an intact re-entry of signals from V5 to V1 is
      essential for the conscious perception of visual motion, the results obtained
      with stimulation of V1 must be caused by a disruption of the re-entrant signals
      from V5 to V1.

PMID- 1360679
TI  - Reversal of female mate choice by copying in the guppy (Poecilia reticulata).
AB  - Ever since Fisher (1958) formalized models of sexual selection, female mate
      choice has been assumed to be a genetically determined trait. Females, however,
      may also use social cues to select mates. One such cue might be the mate choice
      of conspecifics. Here we report the first direct evidence that a female's
      preference for a particular male can in fact be reversed by social cues. In our
      experiments using the Trinidadian guppy (Poecilia reticulata), this reversal was
      mediated by mate-copying opportunities, such that a female (the 'focal' female)
      is given the opportunity to choose between two males, followed by a period in
      which she observes a second female (the 'model' female) displaying a preference
      for the male she herself did not prefer initially. When allowed to choose between
      the same males a second time, compared with control tests, a significant
      proportion of focal females reversed their mate choice and copied the preference
      of the model female. These results provide strong evidence for the role of non
      genetic factors in sexual selection and underlie the need for new models of
      sexual selection that explicitly incorporate both genetic and cultural aspects of
      mate choice.

PMID- 1360680
TI  - Is clutch size in birds affected by environmental conditions during growth?
AB  - Only environmental conditions occurring at the time of breeding have been shown
      to affect clutch size in birds, even though conditions experienced during growth
      are known to affect body size or egg size. We show here that environmental
      conditions experienced during early life can affect clutch size in captive zebra
      finches (Taeniopygia guttata) and wild great tits (Parus major). Not only do
      factors outside the immediate breeding season affect clutch size, but clutch size
      control mechanism is permanently influenced by conditions experienced during
      ontogeny.

PMID- 1360681
TI  - Functional importance of a highly elastic ligament on the mammalian diaphragm.
AB  - The diaphragm of mammals is a musculotendinous dome separating the thoracic and
      abdominal cavities. With no skeletal elements to stretch it, the diaphragm has
      the problem of positioning its muscle fibres at a length appropriate for the
      onset of an inspiratory contraction. This is achieved through a negative
      intrapleural pressure, resulting from the opposing elastic recoil of the ribcage
      and lungs, which sucks the diaphragm into the thorax and extends the muscle
      fibres. A consequence of this negative pressure is that the diaphragm muscle is
      under tension when inactive during expiration. This is an unusual condition for
      skeletal muscles, which can suffer irreversible changes when stretched to long
      length, or they may respond by growing longer. We now describe a highly elastic
      and resilient diaphragmatic ligament which sets a sarcomere length enabling the
      muscle to use its full operating range, reduces stress on the diaphragm muscle
      fibres, and assists shortening of the diaphragm muscle at the onset of
      inspiration by means of elastic recoil.

PMID- 1360682
TI  - 17 alpha,20 beta-dihydroxy-4-pregnen-3-one 20-sulphate is a potent odorant in
      precocious male Atlantic salmon (Salmo salar L.) parr which have been pre-exposed
      to the urine of ovulated females.
AB  - Electrophysiological recordings from the olfactory epithelium have shown that 17
      alpha,20 beta-dihydroxy-4-pregnen-3-one 20-sulphate (17,20 beta-P-sulphate; a
      conjugate of the oocyte-maturation-inducing steroid in teleosts) is a potent
      odorant in precocious male Atlantic salmon (Salmo salar L.) parr. However, the
      olfactory epithelium of these fish only appeared to be responsive to the steroid
      after stimulation with the urine of ovulated female Atlantic salmon. Immature
      fish did not respond at any time. Stimulation with urine from immature and
      precocious male Atlantic salmon parr did not make the olfactory epithelium of
      precocious male salmon parr responsive to the steroid. 17,20 beta-P-sulphate was
      found in the urines of ovulated females, precocious male parr and mature male
      Atlantic salmon. The findings are discussed in relation to the possible role of
      17,20 beta-P-sulphate in the physiology of Atlantic salmon.

PMID- 1360683
TI  - Anterograde and retrograde effects of synapse formation on calcium currents and
      neurite outgrowth in cultured leech neurons.
AB  - The aim of our experiments has been to analyse how formation of chemical synapses
      affects the distribution of calcium (Ca2+) currents and neurite outgrowth of
      leech Retzius cells. Previous results showed that Ca2+ currents measured in the
      initial process or 'stump' of postsynaptic cells were significantly smaller than
      those in corresponding sites on presynaptic neurons. In the present experiments,
      neurons were plated together in close apposition as pairs or as triads, with the
      tip of one Retzius cell touching the soma of another. Ca2+ currents from selected
      areas of the neuronal surfaces were measured by loose-patch recording before and
      after the formation of chemically mediated synaptic connections, which developed
      in about 8 h. With three cells arranged in a row, the last of the series, which
      was purely postsynaptic (i.e. with no target), also showed a dramatic reduction
      in Ca2+ currents in its initial segment, compared with the currents seen in
      either the first cell (purely presynaptic) or the second cell of the chain (which
      was both postsynaptic to the first cell and presynaptic to the third). This
      suggests that retrograde as well as anterograde effects on Ca2+ currents occurred
      as a result of synapse formation: the Ca2+ currents in the middle cell did not
      decrease although a synapse had been formed on it. To test for additional
      consequences of synapse formation, neurite outgrowth was measured in postsynaptic
      cells and in single cells plated on an extract of extracellular matrix containing
      laminin (ECM-laminin). After 48 h, the total length of neuritic outgrowth in
      postsynaptic cells was only about one third of that in single cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1360684
TI  - A model of bipedal locomotion on compliant legs.
AB  - Simple mathematical models capable of walking or running are used to compare the
      merits of bipedal gaits. Stride length, duty factor (the fraction of the stride,
      for which the foot is on the ground) and the pattern of force on the ground are
      varied, and the optimum gait is deemed to be the one that minimizes the positive
      work that the muscles must perform, per unit distance travelled. Even the
      simplest model, whose legs have neither mass nor elastic compliance, predicts the
      changes of duty factor and force pattern that people make as they increase their
      speed of walking. It predicts a sudden change to running at a critical speed, but
      this is much faster than the speed at which people make the change. When elastic
      compliance is incorporated in the model, unnaturally fast walking becomes
      uncompetitive. However, a slow run with very brief foot contact becomes the
      optimum gait at low speeds, at which people would walk, unless severe energy
      dissipation occurs in the compliance. A model whose legs have mass as well as
      elastic compliance predicts well the relationship between speed and stride length
      in human walking.

PMID- 1360685
TI  - The Cellular and Molecular Biology of Membrane Transport. APS Conference.
      Orlando, Florida, November 4-7, 1992. Abstracts.

PMID- 1360686
TI  - Wegener's granulomatosis, microscopic polyarteritis and pauciimmune crescentic
      necrotizing glomerulonephritis, an overview.

PMID- 1360687
TI  - Suppression of superoxide release from human monocytes by somatostatin-related
      peptides.
AB  - Somatostatin and octreotide share with vasoactive intestinal peptide the property
      of having an inhibitory effect on leukocyte functions. While there are studies
      reporting the inhibitory effect of the latter on respiratory burst in human
      monocytes, no such reports are available about similar inhibitory effects of the
      former. The aim of the present study was to investigate such effects of
      somatostatin and octreotide on human monocytes. Release of superoxide anion from
      monocytes was measured by superoxide dismutase-inhibitable reduction of
      cytochrome c in vitro. Somatostatin 1-14, somatostatin 1-28 and octreotide
      inhibited release of superoxide anion from stimulated monocytes. Formylpeptide
      stimulated reduction of cytochrome c was inhibited by 1 mumol/l of octreotide and
      somatostatin 1-14 by about 50% and 35%, respectively. The effect was dose
      dependent with half-maximal effective peptide concentrations at about 10 nmol/l.
      Somatostatin 1-28, which is the major form found in circulating plasma, also
      antagonized formylpeptide-stimulated respiratory burst activity; when directly
      compared to the effect of 1 mumol/l of somatostatin 1-14, somatostatin 1-28 was
      significantly more active (P less than 0.05). Our observations suggest that
      somatostatin-related peptides have a regulatory role in oxygen radical metabolism
      and a mediator role in the neuro-immune axis.

PMID- 1360688
TI  - Insertion and internalization of vasoactive intestinal peptide (VIP) receptors in
      murine CD4 T lymphocytes.
AB  - The specific binding of vasoactive intestinal peptide (VIP) to murine lymphocytes
      was investigated. CD4 T cells from mesenteric lymph nodes (MLN) bound more 125I
      VIP than did unseparated MLN lymphocytes at 37 degrees C, but not at 4 degrees C.
      The differences between the amount of 125I-VIP bound by the CD4 T cells and
      unseparated MLN lymphocytes at 37 degrees C depended upon a difference in the
      amount of the ligand that was internalized by the cells. The rate of insertion of
      unoccupied VIP receptors from the cytoplasm into the cell membrane (370
      receptors/cell/min), the rate constants for internalization of ligand occupied
      VIP receptors (0.55 min-1) and unoccupied VIP receptors (0.11 min-1), and the
      rate constant for the elimination of internalized VIP (0.07 min-1) by CD4 T cells
      were evaluated. These results provide new understanding of the behaviour of VIP
      receptors on lymphocytes and indicate a mechanism by which CD4 T lymphocytes can
      homologously regulate their surface expression of VIP receptors in the presence
      of ambient VIP.

PMID- 1360689
TI  - Anxiolytic-like effect of neuropeptide Y (NPY), but not other peptides in an
      operant conflict test.
AB  - The peptide messengers neuropeptide Y (NPY), growth hormone-releasing hormone
      (GHRH), atrial natriuretic peptide (ANP) and beta-endorphin (BEND) were tested in
      an animal model of anxiety, the Geller-Seifter conflict test. Rats were subjected
      to a multiple schedule consisting of three components: in the first component,
      lever-pressing produced food-reward ('unpunished responding'). The second
      component was a time-out period, during which lever-pressing had no consequences.
      During the third component, lever-pressing produced food-reward, but was also
      punished by an incremental foot-shock ('punished responding'). After establishing
      a stable baseline of both unpunished and punished responding, animals were
      injected with various doses of NPY, GHRH, ANP, BEND, or with saline into the
      lateral cerebral ventricle, and testing was repeated. While changes in unpunished
      responding can reflect alterations in performance factors or motivational
      strength, increases in punished responding have previously been shown to be
      highly specific for anxiety-reducing drugs, such as the benzodiazepines. NPY
      markedly and dose-dependently increased punished responding. A smaller increase
      of unpunished responding was also seen. These results add further support to the
      hypothesis that NPY may be an endogenous anxiolytic. GHRH, ANP and END did not
      affect punished responding.

PMID- 1360690
TI  - TNF alpha-mediated tissue damage in mouse footpads primed with mycobacterial
      preparations.
AB  - Tissue sites involved in certain types of inflammation become sensitive to the
      destructive effect of a subsequent injection of tumour necrosis factor alpha (TNF
      alpha). To try to further delineate the cascade of effector and regulatory events
      controlling this activity, a new model is described and its main properties
      characterized. C57BL/GrFa mice received mycobacterial products subcutaneously in
      the footpads. Recombinant TNF alpha was injected 24 h later into the same sites.
      To assess the tissue-destructive effect of TNF alpha in these "primed" footpads,
      swelling and haemoglobin content of injected footpads were measured, 16 h and 20
      h respectively after the injection of TNF alpha. When loaded with either
      Escherichia coli LPS (10 micrograms) or Mycobacterium vaccae soluble sonicate (17
      micrograms), footpads were reactive to the subsequent injection of 1 microgram
      recombinant TNF alpha, as assessed by both swelling and haemoglobin content. When
      C57BL/GrFa mice received 10(9) autoclaved M. vaccae subcutaneously in the back 10
      days before the footpad was "primed" with soluble M. vaccae sonicate, the
      destructive effect of TNF alpha was significantly enhanced, becoming 5-10-fold
      greater than that seen in sites "primed" with an optimal dose of LPS. This higher
      reactivity was abrogated by a single dose of anti-CD4 given just before the
      injection of TNF alpha. This local reactivity to TNF alpha of skin sites loaded
      with mycobacterial products is compared to the local LPS-dependent Shwartzman
      reaction, and the relevance of this assay as a model with which to delineate the
      mechanisms of tissue damage in tuberculosis is discussed.

PMID- 1360691
TI  - New concepts in the mechanisms of CD4+ lymphocyte depletion in AIDS, and the
      influence of opportunistic infections.

PMID- 1360692
TI  - Genetic markers for the epidemiology of tuberculosis.

PMID- 1360693
TI  - Epidemiological and genetic markers, virulence factors and intracellular growth
      of Mycobacterium avium in AIDS.

PMID- 1360694
TI  - Polyamines are involved in retinoic acid-mediated induction of tissue
      transglutaminase in human peripheral blood monocytes.
AB  - The differentiation of human peripheral blood monocytes (HPBM) into macrophages,
      when cultured in vitro, has been associated with an increase in the expression of
      tissue transglutaminase (TGc). Retinoic acid (RA) addition to 5-day-old cultured
      monocytes, 36 h later induced about 5-folds increase of TGc content. The
      preliminary exposure of cultured monocytes to alpha-difluoromethylornithine
      (DFMO) significantly reduced TGc induction caused by RA. DFMO alone does not
      induce significant changes in the time-course of TGc activity. In cultured
      monocytes exposed to DFMO, putrescine and spermidine, but not spermine were
      significantly depleted. The supplementation of putrescine (1 mM) or spermidine
      (0.5 mM) to culture medium reversed the inhibiting effect of DFMO on RA-mediated
      induction of TGc. However, the addition of polyamines in the absence of RA or
      DFMO did not mimic the induction of TGc by RA. We conclude that TGc induction by
      RA during in vitro maturation of monocytes to macrophages may be modulated by
      polyamine availability.

PMID- 1360695
TI  - The Bietti Foundation: 3rd International Congress on Vitreoretinal Surgery.
      Selected proceedings. Rome, Italy, September 12-16, 1991.

PMID- 1360696
TI  - Extra-axial suppurations of the central nervous system.

PMID- 1360697
TI  - The treatment of the restless leg syndrome with or without periodic leg movements
      in sleep.
AB  - There are presently three main treatments for restless leg syndrome-periodic leg
      movements in sleep (RLS-PLMS). The benzodiazepines (especially clonazepam) are
      considered by most clinicians to be the treatment of choice in mild cases,
      especially in young subjects. In our experience, however, L-dopa and
      bromocriptine are more effective treatments, although no controlled studies have
      ever been conducted to compare their therapeutic benefits and the side effects of
      benzodiazepines and dopaminergic drugs. The use of opioids should be restricted
      to patients who have severe symptoms and who fail to respond to benzodiazepines
      or L-dopa. Propoxyphene was found less effective than L-dopa in decreasing PLMS,
      but some patients resistant to L-dopa may exhibit a masked therapeutic response
      to opioids. However, there is currently no method to predict the response to any
      treatment modality.

PMID- 1360698
TI  - The beneficial effects of one treatment session and recording of nightmares on
      chronic nightmare sufferers.
AB  - Twenty subjects with chronic nightmares for 17.2 years mean duration were
      randomly divided into two groups: Rehearsal and Recording. At inception, subjects
      in both groups were instructed to write down their nightmares for one month. The
      Recording group received no other intervention. Rehearsal subjects received a
      single treatment group session teaching an imagery rehearsal technique to reduce
      nightmare frequency. At inception and three months follow-up, both groups were
      compared for nightmare frequency and for self-rated distress with scales (Symptom
      Checklist and Symptom Questionnaire) measuring anxiety, depression, hostility,
      somatization and total distress. Nightmare frequency decreased significantly in
      both groups: Rehearsal group-7.2 per month to 2.0 per month (72% reduction) (p <
      0.006); Recording group-9.4 per month to 5.0 per month (47% reduction) (p <
      0.02). There were no statistically significant differences in the nightmare
      frequency reductions between groups. All anxiety, depression, somatization,
      hostility and total distress scores decreased substantially in the Rehearsal
      group. Most changes were significant. Changes in the Recording group were
      inconsistent and not significant. Two brief case histories are presented.

PMID- 1360700
TI  - [Problems, failures, complications. A report on the 5th Munich Symposium for
      Scientific Dentistry, Osseointegration IV].

PMID- 1360699
TI  - Long-term double-blind study on the influence of dietary fibres on faecal bile
      acid excretion in juvenile ulcerative colitis.
AB  - A double-blind cross-over long-term trial (18 months) with randomized
      supplementation with wheat fibre or ispaghula for two periods of six months,
      separated by a six-month wash-out period with placebo, was performed in ten
      patients with juvenile ulcerative colitis to study the effect on faecal bile acid
      (BA) excretion. All patients were in remission since 0.5-2 years and orally
      treated with sulphasalazine. The average intake of either fibres was 16 g day-1.
      Faecal samples were collected (72 h) before and after each fibre period. Faecal
      water were prepared by centrifugation of faeces at 15,000 g for 2 h. BA in faeces
      and faecal water were studied using capillary column gas-liquid chromatography
      mass spectrometry. Faecal excretion of total BA were not significantly changed by
      the two fibres. Supplementation with wheat fibre, but not with ispaghula,
      decreased the faecal concentration of total BA by 43% (p < 0.05), unconjugated BA
      by 41% (p < 0.01), and taurine conjugated BA by 58% (p < 0.05). Addition of wheat
      fibre decreased the concentration of chenodeoxycholic acid by 66% (p < 0.05) and
      isomers of cholic acid by 51% (p < 0.05) in faeces. The mean faecal water
      concentration of taurine-conjugated BA decreased by 55% when wheat fibre was
      added (p < 0.05) and the concentration of isomers of deoxycholic acid increased
      by 39% when ispaghula was supplemented (p < 0.05). The ratio isomeric deoxycholic
      acid to deoxycholic acid in faecal water increased significantly when wheat fibre
      was added (p < 0.05). The percentage distribution of secondary and ketonic BA was
      not influenced by the dietary fibre supplementation. The concentration of BA in
      faeces and faecal water decreased only by wheat fibre, suggesting that it is
      superior in obtaining an affect on faecal BA concentration.

PMID- 1360701
TI  - [Mouth mucosal diseases. A report on the 43rd annual meeting of the Study Group
      for Maxillofacial Surgery of the German Society for Dentistry, Oral Medicine and
      Orthodontics in Bad Homburg v.d.H].

PMID- 1360702
TI  - Induction of mucosal and systemic immunity to a recombinant simian
      immunodeficiency viral protein.
AB  - Heterosexual transmission through the cervico-vaginal mucosa is the principal
      route of human immunodeficiency virus (HIV) infection in Africa and is increasing
      in the United States and Europe. Vaginal immunization with simian
      immunodeficiency virus (SIV) had not yet been studied in nonhuman primates.
      Immune responses in macaques were investigated by stimulation of the genital and
      gut-associated lymphoid tissue with a recombinant, particulate SIV antigen.
      Vaginal, followed by oral, administration of the vaccine elicited three types of
      immunity: (i) gag protein p27-specific, secretory immunoglobulin A (IgA) and
      immunoglobulin G (IgG) in the vaginal fluid, (ii) specific CD4+ T cell
      proliferation and helper function in B cell p27-specific IgA synthesis in the
      genital lymph nodes, and (iii) specific serum IgA and IgG, with CD4+ T cell
      proliferative and helper functions in the circulating blood.

PMID- 1360703
TI  - Roles of SWI1, SWI2, and SWI3 proteins for transcriptional enhancement by steroid
      receptors.
AB  - The SWI1, SWI2, and SWI3 proteins, which are required for regulated transcription
      of numerous yeast genes, were found also to be essential for rat glucocorticoid
      receptor function in yeast; the receptor failed to activate transcription in
      strains with mutations in the SWI1, SWI2, or SWI3 genes. Certain mutations in
      genes encoding components of chromatin, identified as suppressors of swi
      mutations, partially relieved the SWI- requirement for receptor function.
      Immunoprecipitation of glucocorticoid receptor derivatives from wild-type (SWI+)
      yeast extracts coprecipitated the SWI3 protein; such receptor-SWI3 complexes were
      not detected in swi1- or swi2- mutant strains, implying that a complex of
      multiple SWI proteins may associate with the receptor. Prior incubation of a
      Drosophila embryo transcription extract with the yeast SWI3-specific antibody
      inhibited receptor function in vitro whereas the antibody had no effect if added
      after initiation complex formation. Thus, positive regulation by the
      glucocorticoid receptor in vivo and in vitro appears to require its interaction,
      at an early step, with one or more SWI proteins.

PMID- 1360705
TI  - Thermal stability comparison of purified empty and peptide-filled forms of a
      class I MHC molecule.
AB  - A secreted form of a class I major histocompatibility complex (MHC) molecule was
      denatured and renatured in vitro in the absence of peptide. The resulting empty
      class I heterodimer was immunologically reactive and structurally similar to a
      heterodimer renatured in the presence of an appropriate restricted peptide.
      Thermal stability profiles indicated that the two forms of heterodimer differed
      in their resistance to denaturation by heat but that a significant portion of the
      empty class I heterodimers had a native conformation at physiological
      temperatures. Free energies calculated from these data gave a direct measure of
      the stabilization of the class I MHC molecule that resulted from peptide binding.

PMID- 1360704
TI  - Overexpression of a transporter gene in a multidrug-resistant human lung cancer
      cell line.
AB  - The doxorubicin-selected lung cancer cell line H69AR is resistant to many
      chemotherapeutic agents. However, like most tumor samples from individuals with
      this disease, it does not overexpress P-glycoprotein, a transmembrane transport
      protein that is dependent on adenosine triphosphate (ATP) and is associated with
      multidrug resistance. Complementary DNA (cDNA) clones corresponding to messenger
      RNAs (mRNAs) overexpressed in H69AR cells were isolated. One cDNA hybridized to
      an mRNA of 7.8 to 8.2 kilobases that was 100- to 200-fold more expressed in H69AR
      cells relative to drug-sensitive parental H69 cells. Overexpression was
      associated with amplification of the cognate gene located on chromosome 16 at
      band p13.1. Reversion to drug sensitivity was associated with loss of gene
      amplification and a marked decrease in mRNA expression. The mRNA encodes a member
      of the ATP-binding cassette transmembrane transporter superfamily.

PMID- 1360706
TI  - [Effect of opioid peptides on progesterone production by rat luteal cells in
      vitro].
AB  - The effect of exogenous opioid peptides on progesterone production by incubated
      rat luteal cells was studied. beta-endorphin (beta-EP) stimulated progesterone
      production in a dose-dependant manner (10(-8)-10(-6) mol/L); dynorphin exhibited
      a stimulatory effect only at 10(-6) mol/L, while Met-enkephalin had no
      substantial effect at dose from 10(-10)-10(-6) mol/L. mu-opioid receptor agonists
      DAGO and morphine also stimulated progesterone production. The stimulatory
      actions of beta-EP, DAGO and morphine were reversed completely by naloxone. On
      account of the fact that the beta-EP level in rat plasma is lower than that in
      the ovary, it seemed that beta-EP may be an intra-ovarian luteotrophic factor and
      be involved in the regulation of progesterone production. This action of beta-EP
      may be mediated by mu-opioid subtype receptors.

PMID- 1360707
TI  - [Effects of electrical lesioning of hippocampal CA3 region and anterior
      commissura hippocampi fornix on plasma insulin level and islet cells in the rat].
AB  - Bilateral electrical lesioning of the hippocampal CA3 region (HCA3-EL) or
      anterior commissura hippocampi (ACHF-EL) caused marked elevations in plasma basal
      levels of insulin. 2 weeks later, fasting blood glucose levels were also
      augmented with decreased glucose tolerance. In contrast, the secretory response
      of pancreatic B cells to glucose stimulation was markedly enhanced. Following
      intravenous glucose tolerance test (IVGTT), the relative amounts of glucagon-like
      and insulin-like immunoreactants were reduced in the pancreatic islets of both
      HCA3-EL and ACHF-EL rats in comparison with the controls. In the HCA3-EL group,
      the relative amounts of somatostatin-like immunoreactants and gross numbers of
      such immunostained cells in islets were also decreased as compared with the
      control. No difference was seen in pancreatic-polypeptide-like immunoreactivities
      as assessed by immunohistochemistry plus microphotometry method. The above
      results suggest strongly that HCA3 and ACHF exert a tonic inhibitory action on
      the insulin secretion in the rat.

PMID- 1360708
TI  - Effect of H2 antagonists on outcome of simple closure for perforated duodenal
      ulcer.
AB  - The treatment of perforated duodenal ulcer is controversial. Since the advent of
      H2 antagonists, the number of ulcer operations has declined tremendously. We
      wanted to find out if the addition of a H2 antagonist after simple closure of a
      perforated duodenal ulcer would change the outcome and therefore reviewed 46
      patients treated in this fashion. Our results show that this is a safe and
      effective way of treating patients with perforated duodenal ulcer.

PMID- 1360709
TI  - Role of pancreatoduodenectomy in the management of primary duodenal wall
      gastrinomas in patients with Zollinger-Ellison syndrome.
AB  - BACKGROUND: The role of pancreatoduodenectomy in the surgical management of
      duodenal wall gastrinomas (DWGs) has not been well established. Recently DWGs
      have been recognized with increasing frequency, and several reports have
      emphasized that pancreatoduodenectomy can now be performed with a low operative
      morbidity and mortality for other conditions. The purpose of this study was to
      determine the indications, safety, and efficacy of pancreatoduodenectomy in the
      treatment of DWGs. METHODS: Forty-five patients with Zollinger-Ellison syndrome
      were evaluated and surgically treated between 1960 and 1991; 15 (33%) of these
      had primary DWGs. RESULTS: Pancreatoduodenectomy was considered necessary for
      curative resection in six patients. Two of these patients had multiple
      gastrinomas as part of multiple endocrine neoplasia type 1 syndrome and underwent
      tumor excisions and total gastrectomy; both died of tumor-related complications
      (survival, 8.5 and 12 years). A third patient did not consent to
      pancreatoduodenectomy, underwent total gastrectomy and tumor excision, and also
      died of tumor-related complications (survival, 10 years). The remaining three
      patients underwent pancreatoduodenectomy. After pancreatoduodenectomies were
      performed, these three patients became and remained eugastrinemic with normal
      results from secretin stimulation tests (mean follow-up, 7.5 years). CONCLUSIONS:
      In patients with DWGs and Zollinger-Ellison syndrome, pancreatoduodenectomy
      should be considered the treatment of choice whenever complete tumor excision is
      not possible by a lesser procedure.

PMID- 1360710
TI  - Gastrin-dependent inhibitory effects of octreotide on the genesis of gastric
      ECLomas.
AB  - BACKGROUND: The efficacy of octreotide in the regulation of endocrine tumor
      secretion and symptomatology has been well documented. Its effects on
      neuroendocrine tumor generation and cell proliferation are less well understood.
      The purpose of this study was to determine if blockade of somatostatin receptors
      by octreotide would alter gastrin levels and influence enterochromaffin-like
      (ECL) cell proliferation. METHODS: The well-established gastric ECLoma model of
      the rodent, mastomys, was used. Animals received loxtidine (1 mg/kg/day), an
      irreversible H2 blocker, and subcutaneous slow release, octreotide pellet
      implants (150 or 300 micrograms/kg/day) or placebo pellets for a 4-month period.
      RESULTS: Control parameters for gastric mucosal thickness, plasma gastrin level,
      ECL cell density, and bromodeoxyuridine-positive cells were 517 +/- 20 microns,
      46.1 +/- 11.4 pmol/L, 7.4 +/- 0.9 cells/visual field, and 13.8 +/- 2.6
      cells/visual field, respectively. After loxtidine-placebo treatment all values
      were significantly increased (p < 0.05; 883 +/- 70 microns, 192.8 +/- 10.6
      pmol/L, 97 +/- 16.2 cells/visual field, and 51.7 +/- 19.2 cells/visual field,
      respectively). High dose octreotide significantly inhibited all parameters (668
      +/- 3.5 microns, 66.2 +/- 20.5 pmol/L, 37.0 +/- 8.0 cells/visual field, and 10.9
      +/- 2.2 cells/visual field; p < 0.05). Low dose octreotide failed to
      significantly inhibit ECL cell density mucosal thickness, or cell proliferation.
      CONCLUSIONS: Irreversible H2 receptor blockade results in hypergastrinemia and
      ECL cell tumor generation. Hypergastrinemia, ECL cell hyperplasia, and cell
      proliferation are significantly inhibited by in vivo blockade of somatostatin
      receptors by administration of octreotide.

PMID- 1360711
TI  - Long-term follow-up of a large North American kindred with multiple endocrine
      neoplasia type 2A.
AB  - BACKGROUND: Sixty-one patients with multiple endocrine neoplasia (MEN) type 2A
      (27 men; 34 women; mean age, 39 years) from a single kindred (76 affected, 49 at
      risk) were followed 1 month to 33 years (median, 14 years) after diagnosis for
      disease expression. METHODS: Peripheral basal and pentagastrin-stimulated
      calcitonin, parathyroid hormone, and calcium levels were measured in 60 patients,
      58 of whom had undergone previous thyroidectomy; the calcitonin concentration in
      four patients was concomitantly determined in the hepatic and internal jugular
      veins. Biochemical or radiographic screening for pheochromocytoma was performed
      in 58 patients. RESULTS: Recurrence of medullary thyroid carcinoma (MTC)
      developed in nineteen (33%) of 58 patients after they underwent thyroidectomies.
      In 14 of 19 patients regional metastases were inapparent at initial operation,
      and lymphadenectomy was not undertaken. Three patients underwent neck
      reexploration with removal of micrometastases after selective venous studies were
      performed. One patient, 33 years of age, died of MTC, and two patients who
      refused thyroidectomy are alive at 76 and 83 years of age. Fifteen patients are
      alive with disease 8 to 33 years after they underwent thyroidectomies. All
      patients identified by prospective screening remain pentagastrin negative.
      Pheochromocytoma developed in six patients (10%), and four patients have
      Hirschsprung's disease. Hyperparathyroidism was present in seven patients and did
      not occur in those with minimal MTC. CONCLUSIONS: These observations suggest that
      (1) the course of MTC in MEN 2A is highly variable, (2) early treatment of C-cell
      disease can be curative, (3) routine lymphadenectomy for occult micrometastases
      may be necessary for cure of MTC, and (4) the hyperparathyroidism of MEN 2A may
      not be a primary genetic event.

PMID- 1360712
TI  - Hyperparathyroidism in multiple endocrine neoplasia syndrome.
AB  - BACKGROUND: We analyzed clinical findings and results of parathyroidectomy in 42
      patients treated from 1936 to 1988 at the University of California, San Francisco
      (UCSF) for primary hyperparathyroidism and multiple endocrine neoplasia (MEN)
      syndrome to document results of parathyroidectomy and reasons for failed
      parathyroid operations. METHODS: Of the 42 patients (38 had MEN 1 syndrome; 4 had
      MEN 2A syndrome), 40 patients were treated surgically: 29 had initial
      parathyroidectomy at UCSF; 11 were referred to UCSF because of MEN syndrome.
      Eight of these 11 patients required reoperation for persistent or recurrent
      hyperparathyroidism. Patients with hyperplasia were treated with subtotal
      parathyroidectomy; the glands of those patients with solitary or double adenomas
      were removed with or without biopsy of the normal appearing glands. RESULTS:
      Overall, in seven (50%) of 14 patients with hyperplasia, three (16%) of 19
      patients with solitary adenoma, and one (14%) of seven patients with double
      adenomas, recurrent or persistent hyperparathyroidism developed. Failure in
      patients with hyperplasia was due to missed supernumerary glands (13%) and missed
      ectopic glands (33%). Failure occurred in patients with solitary (three patients)
      or double (one patient) parathyroid tumors because of unrecognized hyperplasia.
      None of the four patient with MEN 2A syndrome had persistent or recurrent
      disease, but hypoparathyroidism developed in one patient; hypoparathyroidism
      developed in three patients with MEN 1 syndrome. CONCLUSIONS: These data suggest
      that although many patients with primary hyperparathyroidism and MEN syndrome
      have multiple abnormal parathyroid glands, two populations of patients exist; one
      population has solitary or double adenomas and recurrence is uncommon, whereas
      the other population of patients has hyperplasia and persistent or recurrent
      disease is common.

PMID- 1360713
TI  - P-glycoprotein expression and multidrug resistance in adrenocortical carcinoma.
AB  - BACKGROUND: The response of adrenocortical carcinoma (ACC) to adjuvant
      chemotherapy has been disappointing with no significant impact on survival. The
      normal adrenal cortex has very high levels of P-glycoprotein, an energy-dependent
      efflux pump of a variety of structurally unrelated chemotherapeutic agents. P
      glycoprotein has been implicated as a cause of multidrug resistance in a variety
      of neoplasms. The purpose of this study was to evaluate P-glycoprotein expression
      in ACC. METHODS: Eleven patients with ACC had paraffin-embedded tumor evaluated
      for P-glycoprotein expression. These were analyzed by immunohistochemistry assay
      with a battery of four anti-P-glycoprotein antibodies (MRK-16, JSB-1, UIC-2,
      MDR). RESULTS: All eleven cases showed intense, predominantly membrane
      immunoreactivity for P-glycoprotein. In 10 of the cases, most tumor cells were
      immunoreactive with at least three antibodies, and six of 11 cases were positive
      for all four antibodies. In this small series no correlation existed between P
      glycoprotein expression and tumor grade, stage of disease, or survival.
      CONCLUSIONS: All 11 cases of ACC studied showed P-glycoprotein expression, which
      was similar to the normal adrenal cortex. This possible mechanism of multidrug
      resistance may help explain the significant chemoresistance seen in ACC.

PMID- 1360714
TI  - [The comparative efficacy of slow-acting (basic) preparations in psoriatic
      arthritis].
AB  - Overall 126 patients with verified and clinically active psoriatic arthritis (PA)
      were subjected to a randomized study of the efficacy of chrisanolum (Chr),
      sulfasalicylic drugs (SSD) (sulfasalazine and salazopyridazine) and methotrexate
      (MT) as compared to nonsteroidal anti-inflammatory drugs (NSAID). The treatment
      that lasted for a year was completed by 77 patients: in the group on NSAID, by
      31, on Chr by 15, on SSD by 15, and on MT by 16. In the remainder, the treatment
      was discontinued because of side effects. The best clinical effect was recorded
      in patients on Chr. The improvement was observed in 73% of the patients, with a
      significant effect being attained in 60%. In the groups on SSD and MT, the
      improvement was observed in 80 and 69%, respectively. However, noticeable
      improvement was only recorded in 20 and 19%. SSD turned out more effective than
      MT. in the group on NAID, the improvement was ascertained but in 35% of the
      patients, with noticeable one being attained in 6%. According to Pearson's
      criterion chi 2, the results of the treatment with NAID alone were less potent
      than in the group given Chr (p < 0.001) and SSD (p < 0.05). The differences
      between the effect of the treatment with NAID and MT appeared nonsignificant (p >
      0.1). Therefore, according to the diminution of the clinical efficacy in PA, the
      basic drugs may be distributed in the following way: Chr, SSD, MT. The side
      effects in the group on NAID were. recorded in 37% of cases, in the group on Chr
      in 53%, on SSD in 33%, and on MT in 55%. This means that SSD were tolerated best
      of all.

PMID- 1360715
TI  - Modulation of calciuria by cadmium pretreatment in rats with cadmium
      metallothionein-induced nephrotoxicity.
AB  - One group of male Wistar rats (Group B) was pretreated by a daily subcutaneous
      injection with CdCl2 during 5 days with increasing doses (0.5, 1, 1, 2 and 2 mg
      Cd/kg). Another group of rats (Group A) was daily given normal saline
      subcutaneously for 5 days. On the second day after the last injection, a single
      s.c. injection of 109Cd-metallothionein (CdMT, 0.4 mg Cd/kg) was given to each
      animal in both groups. Urinary calcium, protein, metallothionein (MT), N-acetyl
      beta-D-glucosaminidase (NAG) and gamma glutamyltransferase (gamma-GT) were
      measured. In Group A, calciuria, proteinuria, metallothioneinuria and enzymuria
      was induced by CdMT. Calciuria reached a peak during 0-6 h after the
      administration of CdMT, thus appearing earlier than other effects. Enzymuria was
      displayed at 6-12 h for gamma-GT and 12-24 h for NAG. A prominent increase of
      proteinuria appeared at 24-48 h after the challenge of CdMT. In Group B, no
      significant increase of urinary calcium, protein, or NAG was observed after the
      CdMT injection and urinary gamma-GT was only slightly elevated, thus
      demonstrating the protective action of pretreatment. This study demonstrates for
      the first time that calciuria, one of the signs of cadmium nephrotoxicity, can be
      prevented by cadmium pretreatment. Urinary MT increased slightly during the 4-5
      days of CdCl2 pretreatment. This is in accordance with previous observations that
      cadmium pretreatment induces new synthesis of MT which is likely to constitute
      the background for the resistance to the CdMT challenge to the kidney.

PMID- 1360716
TI  - Neurochemical effects in rats following gestational exposure to styrene.
AB  - Styrene was evaluated for the reproductive effects of pregnant rats and the
      neurochemical effects in the offspring of rats exposed during gestation. Pregnant
      Wistar rats were exposed to 0, 50, or 300 ppm styrene for 6 h/day during days 7
      to 21 of gestation. No significant differences in the number of offspring
      delivered were observed between the exposed and control groups. Body weights at 1
      day of age of the offspring whose mothers were exposed to styrene were
      significantly lower than those of the control group. Although, there were neither
      statistically significant differences of protein contents nor brain weights among
      styrene-exposed and their control offsprings of rats, analyses of
      neurotransmitter studies showed dose-dependent decreases of neuroamines,
      especially 5-HT (serotonin) and its metabolite 5HIAA (5-hydroxyindoleacetic acid)
      in the newborn offspring of styrene-exposed rats. The results suggest that
      gestational exposure to styrene at these concentrations does not produce apparent
      reproductive toxicity but affects the body weight of pups and causes lowering of
      the neurotransmitter levels in the brain.

PMID- 1360718
TI  - [The 5th All-Union Congress of Protozoologists. September 1992. Abstracts].

PMID- 1360717
TI  - Receptor classes and the transmitter-gated ion channels.
AB  - Transmitter-gated channels, which can be selective for cations or for anions,
      form an important class among the membrane receptors responsible for signal
      transduction. Thirteen principal types of these channels can now be recognized
      and most of these are available for analysis in recombinant form. It is
      instructive to contrast their characteristic structural features with those of
      the two other primary classes of the signal-transducing receptors of membranes.

PMID- 1360720
TI  - Immunohistochemical localization of c-erbB-2 protein and epidermal growth factor
      receptor in normal surface epithelium, surface inclusion cysts, and common
      epithelial tumours of the ovary.
AB  - The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor
      receptor showing molecular homology with the epidermal growth factor receptor
      (EGFR). We examined the immunohistochemical reactivity of monoclonal antibodies
      against both of these proteins in normal surface epithelium, surface inclusion
      cysts, and common epithelial tumours of the ovary. The ovarian tumours were
      classified as benign (16), borderline malignant (2), and malignant (19). Normal
      surface ovarian epithelium was weakly positive for both c-erbB-2 protein and
      EGFR. In surface inclusion cysts, however, the epithelial cells lining the lumen
      exhibited stronger staining for c-erbB-2 protein, but no staining for EGFR. All
      16 benign ovarian tumours and the 2 borderline malignant ovarian tumours were
      positive for c-erbB-2 protein and negative for EGFR. Of the ovarian carcinomas,
      13 of the 19 (68.4%) were positive for c-erbB-2 protein and negative for EGFR,
      while 4 showed positivity for both c-erbB-2 protein and EGFR. Two cases were
      negative for both proteins. Expression of both c-erbB-2 protein and EGFR was
      found in endometrioid carcinoma with squamous differentiation and in clinically
      advanced poorly differentiated serous carcinomas. Expression of c-erbB-2 protein
      appears to be increased and that of EGFR is reduced in the early stage of
      epithelial ovarian oncogenesis. The expression of EGFR with c-erbB-2 protein in
      ovarian carcinoma is related both to histological differentiation and/or advanced
      clinical stage.

PMID- 1360722
TI  - Modulation of KB and A431 cell adhesion by epidermal growth inhibitory
      pentapeptide.
AB  - A pentapaptide, pyroGlu-Glu-Asp-Ser-GlyOH (EPP), isolated from mouse epidermis,
      inhibits mitoses and enhances differentiation in primary cultures and in
      transformed mouse epidermal cells in vitro (Elgjo et al. 1986 b). The present
      work demonstrates that EPP also modulates the adhesiveness of two human tumour
      cell lines (KB and A431) of epidermal origin to uncoated plastic and to plastic
      coated with fibrinogen or collagen type 1. The adhesion modulatory effect of EPP
      was observed over a broad range of concentrations (10(-12)-10(-6) M), and
      depended on the substrate the cells were growing on. Thus, when cells were seeded
      on plastic or collagen, the attachment to the substrate was suppressed at the
      highest concentrations of EPP, and stimulated at the lowest ones. The opposite
      concentration-response pattern was observed when fibrinogen was used as
      substrate.

PMID- 1360721
TI  - Storage of glycoprotein in NCTR-Balb/C mouse. Lectin histochemistry, and
      biochemical studies.
AB  - A strain of Balb/C mice carrying a lysosomal storage disorder exhibits metabolic
      and phenotypic abnormalities similar to patients with sphingomyelin-cholesterol
      lipidoses type II (i.e., Niemann-Pick C and D). Their foamy cells, which belong
      to the reticuloendothelial system, stained intensely by periodate-Schiff (PAS)
      reagent and were resistant to predigestion with diastase. To identify the
      chemical nature of the PAS-positive storage material, we applied lectin
      histochemistry and biochemical methods. Paraffin embedded sections, and
      delipidated frozen tissue sections, were treated with biotinylated lectins and
      localized with avidin-biotin-peroxidase complex. Araldite-embedded semithin
      sections were incubated with biotinylated lectins followed by avidin-gold and
      were enhanced with silver. By both histochemical methods the affected foamy cells
      stained positively as follows: Concanavalia ensiformis agglutinin, Datura
      stramonium agglutinin, Griffonia simplicifolia-I, Lens culinaris agglutinin,
      peanut agglutinin, Ricinus communis agglutinin-I, wheat germ agglutinin (WGA),
      and succinylated-WGA. Biochemical analysis of liver extracts complemented the
      histochemical data and demonstrated accumulation of glycoproteins containing
      polylactosaminoglycans in affected mice. Our findings indicate that the storage
      material in NCTR-Balb/C mice is heterogeneous. The lipids that are extracted by
      organic solvents during the histologic preparations mask the occurrence of
      polylactosaminoglycan containing glycoproteins in native frozen sections.

PMID- 1360719
TI  - Human cytomegalovirus in the pancreas of patients with type 2 diabetes: is there
      a relation to clinical features, mRNA and protein expression of insulin,
      somatostatin, and MHC class II?
AB  - Human cytomegalovirus (HCMV) was recently demonstrated in the pancreas of about
      half the patients with type 2 diabetes mellitus in the absence of mumps, rubella
      or Coxsackie B virus. The present study addresses the question as to whether type
      2 diabetes with an HCMV-positive pancreas differs from those with HCMV-negative
      pancreases with respect to age, sex, treatment, duration of disease, volume
      densities of B-cells and D-cells, mRNA levels of insulin and somatostatin, islet
      amyloid peptide deposits and major histocompatibility complex (MHC) class I and
      class II gene transcription, and protein expression. HCMV-positive type 2
      diabetic patients showed a tendency towards a shorter duration of disease and
      significantly increased levels of MHC class II on RNA. In addition, expression of
      MHC class II product (HLA-DR) was identified in duct epithelial cells and/or
      islet cells in 9 diabetic pancreases and in 2 non-diabetic glands. No MHC class I
      expression could be detected. No other clinical differences between HCMV-positive
      and HCMV-negative glands were found. All 10 HCMV-positive diabetics showed a
      strong expression of MHC class II mRNA in the pancreas. By immunocytochemistry, 4
      of 10 demonstrated expression on the islets; three of ten also expressed MHC DR
      beta on ductal cells. This finding might be related to the viral infection, as
      only 2 of the 9 HCMV-negative patients were HLA-DR beta positive and none of the
      non-diabetic controls showed increased levels of MHC class II mRNA. These data
      suggest that HCMV infection in the pancreas is associated with type 2 diabetes.
      However, no conclusions as to a role of this virus in the aetiopathology of type
      2 diabetes can be drawn at present.

PMID- 1360723
TI  - Influence of estrogen and progesterone on the induction of mammary carcinomas by
      7,12-dimethylbenz(a)anthracene in ovariectomized rats.
AB  - The influence of estrogen on mammary carcinogenesis was studied in female Sprague
      Dawley rats ovariectomized at the age of 36 days and given injections of 17 beta
      estradiol (group I:0, II:1, III:10, IV:100, V:1000 micrograms/2 days) between the
      ages of 36 and 250 days and a single oral dose of 20 mg of 7,12
      dimethylbenz(a)anthracene (DMBA) at the age of 50 days. No palpable mammary
      carcinomas were detected up to the age of 135 days. At the age of 135 days, each
      group was divided into two subgroups (a and b). Rats of the second subgroup (Ib,
      IIb, IIIb, IVb and Vb) were given additional injections of progesterone (P; 4
      mg/2 days) between the ages of 135 and 250 days. At the age of 250 days, the
      incidence of mammary carcinoma was significantly higher in rats from group IIIb
      than in groups Ib and IIIa, and that in group IVa was also higher than in group
      Ia. The incidence in group IVb was significantly lower than in group IVa. The
      carcinomas in group IIIb were palpable papillo-tubular adenocarcinomas and those
      in group IVa were secretory micro-adenocarcinomas. These results indicate that
      the induction of mammary carcinomas by DMBA is totally inhibited by ovariectomy
      and/or high doses of estrogen, but that mammary carcinomas are initiated by DMBA
      under hormonal conditions in which suitable levels of estrogen are present. They
      also suggest that the growth of DMBA-induced mammary carcinomas in the rats from
      group III were accelerated by additional injections of P and that those in rats
      from group IV were inhibited by additional P.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360724
TI  - Promoting effect of ovariectomy on hepatocellular tumorigenesis induced in mice
      by 3'-methyl-4-dimethylaminoazobenzene.
AB  - The treatment of female C57BL/6 x DS-F1 mice with 3'-methyl-4
      dimethylaminoazobenzene (3'-Me-DAB) at 10, 12, 14, 16 and 18 days of age resulted
      in the development of hepatocellular adenomatous nodules after 10 months of age.
      Ovariectomy in these mice at 1 month of age hastened the development of
      adenomatous nodules, which then first appeared at 8 months of age. The incidence
      of adenomatous nodules in females ovariectomized at the age of 1 month was much
      higher than that in intact females of the same age. These results showed that the
      ovaries exerted a suppressive effect on the development of adenomatous nodules.
      To determine the time from which the ovaries exert this suppressive effect,
      females were ovariectomized at 4, 6, 8, and 10 months of age, and the incidences
      of adenomatous nodules were compared at 10 and 12 months of age. Delayed
      ovariectomy after 8 months of age did decrease the incidence of adenomatous
      nodules at 10 and 12 months of age, but ovariectomy after 4 and 6 months of age
      did not. When the incidence of adenomatous nodules in females ovariectomized at
      10 months of age was examined over the subsequent 6 months, it became
      significantly higher after 14 months of age compared with that in intact females.
      The results show that the ovariectomy has the promoting effect on the development
      of adenomatous nodules in the liver induced by 3'-Me-DAB after 6 months of age.

PMID- 1360725
TI  - Visualization and rapid quantification of autoradiographic labeling in scanning
      electron microscopy applied to localization of receptor sites on the surface of
      whole cells.
AB  - The use of backscattered electron imaging (BEI) as a routine procedure for
      examining autoradiographic reactions in scanning electron microscopy (SEM) is
      described. This technique allows the determination of the number of receptor
      sites occupied by 125I-epidermal growth factor (EGF) on whole cells. The effect
      of 1.25 dihydroxyvitamin D3 (1,25 (OH)2D3) on the number of epidermal growth
      factor receptors (EGF-R) in the BT 20 human mammary carcinoma cell line (which is
      known to possess a very high number of EGF-R) has been evaluated with this
      method. To compare the silver grain density over the cells (controls and 1,25
      (OH)2D3-treated cells) we used an image analysis system Quantimet 900. The
      results were compared with those of a previous study using transmission electron
      microscopy (TEM). This study confirmed the results obtained with TEM and showed
      the even distribution of receptors sites on a single cell and a large difference
      in the number of receptor sites from one cell to another. The use of BEI to
      visualize the autoradiographic reaction in SEM allowed the examination of a large
      surface with good contrast and resolution and eliminated artefacts not
      corresponding to the silver grains. It gave new information not delivered by
      quantitative TEM autoradiography and was easier and faster to use. The efficient
      use of SEM autoradiography combined with BEI could facilitate whole area
      distribution mapping of radioactive labeling.

PMID- 1360726
TI  - Responses of enterocyte microvilli in experimental diabetes to insulin and an
      aldose reductase inhibitor (ponalrestat).
AB  - The small intestine of 12-week-old streptozotocin-diabetic rats was examined by
      light and transmission electron microscopy in order to study the effects of
      alternative treatments on microvillous morphology. Four groups were examined:
      untreated diabetic rats, insulin-treated diabetics and rats treated with an
      aldose reductase inhibitor (ponalrestat) given with and without insulin. Numbers
      and dimensions of microvilli at the apex of columnar absorptive epithelial cells
      (enterocytes) were estimated using stereological principles. Values were obtained
      for the organ as a whole as well as for different sites along its length. In the
      untreated diabetic intestine, the mean (standard error of mean) number of
      microvilli was 4.5 (0.8) x 10(12) with a total surface area of 1.9 (0.50) m2. On
      average, the microvilli were 1.1 (0.08) microns long, 104 (3.8) nm in diameter
      and packed on the villous surface at a density of 3400 (50) per 100 microns 2.
      Their length at least varied with intestinal location. Significant effects of
      insulin therapy were detected. In contrast, the study failed to find any
      significant effect of aldose reductase inhibition on any variable except
      microvillous packing density.

PMID- 1360727
TI  - Biochemical and immunohistochemical studies on overgrown gingival tissues
      associated with mannosidosis.
AB  - The gingival tissues of a male patient suffering from mannosidosis and presenting
      with gingival overgrowth have been studied. Routine histological assessment
      highlighted the presence of highly enlarged and vacuolated lymphocytes. The
      morphology of the connective tissues, fibroblasts and epithelium appeared normal.
      Immunohistochemical staining of the tissues for chondroitin sulfate proteoglycan
      demonstrated a normal distribution of this component throughout the connective
      tissues and intense staining associated with the vacuolated lymphocytes. In vitro
      studies indicated that fibroblasts isolated from the overgrown tissue did not
      differ from age and sex matched control fibroblasts with respect to
      proliferation, protein and proteoglycan synthesis. Taken together, these findings
      imply that the gingvial overgrowth noted in this patient was not due to a defect
      in the resident fibroblasts but rather reflected a secondary response to the
      tissues to impaired host defence mechanisms.

PMID- 1360728
TI  - [Specialized medical care in combat-related pathology (based on materials from
      the scientific and practical conference of physicians of the N. N. Burdenko Main
      Military Clinical Hospital)].

PMID- 1360730
TI  - [The prospects and problems of drug-induced anesthesia].
AB  - The problem of pain has a major medico-social significance and necessitates
      detailed investigation both from the position of etiology and pathogenesis and
      new therapy methods. Among many methods of pain control drug-induced anesthesia
      is of great importance. The multiplicity of pain requires optimal use of
      analgetics and their combination with other agents strictly in coordination with
      individual needs of the patient. Special anesthesia systems are to be designed
      for this purpose.

PMID- 1360729
TI  - [The clinical and neuromediator mechanisms of the analgetic action of decimeter
      waves and deresinated naphthalan in patients with humeroscapular periarthrosis].

PMID- 1360731
TI  - [Tertatolol--characteristics of the drug].

PMID- 1360733
TI  - Effects of adrenaline, dopamine, serotonin, and different cholinergic agents on
      smooth muscle preparations from the ansa proximalis coli in cattle: studies in
      vitro.
AB  - The effects of adrenaline, dopamine, serotonin, and different cholinergic agents
      on isolated muscle strips from the ansa proximalis coli in cattle were studied.
      Adrenaline (5 x 10(-5) mol/l) evoked a relaxing effect (p < 0.05) on longitudinal
      and circular muscle strips, mediated via beta- and alpha 1-receptors
      respectively. High concentration of dopamine (5 x 10(-4) mol/l) caused a non
      significant inhibitory effect on longitudinal smooth muscles, which was probably
      mediated by beta- and not by dopamine-receptors. Serotonin (5 x 10(-5) mol/l) and
      cisapride (75 x 10(-6) mol/l) had no effect. Carbachol (2 or 10 x 10(-6) mol/l)
      and bethanechol (5 or 10 x 10(-5) mol/l) caused a dose-dependent (p < 0.05)
      contraction of both smooth muscle types. This excitatory effect was inhibited (p
      < 0.05) by metoclopramide (1 x 10(-4) mol/l), as well as the muscarinic agents RS
      86 (5 x 10(-5) mol/l) and CGP-37,218 (37.5 or 75 x 10(-6) mol/l).

PMID- 1360732
TI  - Advantages of achiral h.p.l.c. as a preparative step for chiral analysis in
      biological samples and its use in toxicokinetic studies.
AB  - 1. Achiral reverse-phase h.p.l.c. with semi-automated post-column fraction
      collection and solid-phase sample reconcentration, has been applied as the
      purification procedure during the enantiomeric quantification of two widely
      differing experimental drugs; an HMG-CoA reductase inhibitor (I) and an alpha 2
      adrenoceptor antagonist (II). 2. The robust and specific achiral methodologies
      were available prior to the need for chiral analyses and recovery of drug from
      the fractions provided clean samples from a variety of biological matrices,
      without the need to develop compatible achiral/chiral mobile phases. 3. Compared
      with direct chiral chromatography of plasma extracts, this approach decreased the
      potential for metabolites and endogenous components to interfere or impair the
      performance of the chiral stationary phase. 4. The availability of quantitative
      data from achiral analysis of samples negated the need for internal
      standardization of the chiral analyses, helped confirm assay specificity and
      provided potential to determine enantiomeric ratios where only one isomer could
      be accurately measured. 5. Routine enantiomeric analyses were successfully
      carried out on samples taken from animals dosed orally with the racemic drugs,
      providing important data on the possible levels of exposure to individual
      enantiomers during toxicity testing.

PMID- 1360735
TI  - [Use of intravascular laser irradiation of blood in the treatment of drug
      resistant forms of schizophrenia].
AB  - Overall 62 schizophrenic patients resistant to all forms of treatment were
      examined for the clinical efficacy of the treatment method on the basis of
      intravascular laser blood irradiation. A detailed description of the method,
      equipment, optimal doses, and the degree of effect in different
      psychopathological syndromes are provided. The best results were obtained in
      cases where the depressive paranoid symptomatology was predominant. The authors
      give recommendations for practical use of laser therapy under the conditions of
      the psychiatric hospital, discuss its action mechanism.

PMID- 1360734
TI  - [Approach to the optimal therapy of the psycho-autonomic syndrome].
AB  - To potentiate the psycho- and autonomic activity of phenazepam and to decrease
      its side effects, cranio-cervical electrophoresis of the drug is suggested. The
      method is realized with the aid of a special electrode helmet which permits
      localizing electrodes in the frontal and occipital areas and at different levels
      of the lateral surfaces of the neck. Phenazepam in the amount of 1 ml of 3%
      solution was administered from the cathode. 194 patients with the
      psychovegetative syndrome in the clinical structure of neurosis or neurosis-like
      condition were treated. The dynamics of the psycho-vegetative status was verified
      with the aid of psychometric and vegetative techniques. Cerebral hemodynamics was
      investigated by rheoencephalography. The data obtained demonstrate that the
      treatment suggested improves the patients' functional status, decreases reactive
      anxiety, raises the tempo of sensomotor reactions and attention activity,
      ameliorates short-term memory, exerts a sympatholytic action, and makes cerebral
      hemodynamics return to normal. The method produces fewer side effects as compared
      to the enteral intake of phenazepam.

PMID- 1360736
TI  - [Use of plasmapheresis in the complex treatment of patients with endogenous
      psychoses].
AB  - The results of the use of plasmapheresis in multimodality treatment of patients
      with endogenous psychoses are provided for the first time. The use of
      plasmapheresis was shown to be highly effective in overcoming resistance to
      psychotropic agents as well as in the treatment of lingering and chronic
      extrapyramidal neuroleptic disorders. The beneficial effect on the mental and
      neurologic status of the patients is coupled with pronounced immunocorrective
      action of the procedure.

PMID- 1360738
TI  - [Molecular-genetic analysis of Huntington chorea (review of the foreign
      literature)].

PMID- 1360737
TI  - [Various indicators of the hormonal profile in patients with neuroses after
      psychopharmacotherapy and functional test with sinacten].
AB  - Studies of adenohypophyseal hormones, cortisol, T3, T4, thyroxine-binding
      globulin, testosterone, progesterone and estradiol in 90 neurotic men, treated or
      not with amitriptyline and benzodiazepines, allowed a conclusion that in the
      majority of them, endocrine functions were activated. 11 healthy men and 11 male
      patients underwent the three-day test with sinacten-depot (1 mg intramuscularly).
      The functional test data were compared over time by the methods of nonparametric
      statistics. The patients manifested a decrease of reserve potentialities of the
      pituitary-adrenal system, redistribution of the fractions of thyroid hormones,
      gonadotropins, the progesterone/estradiol ratio, a rise of prolactin and
      testosterone secretion. The drugs were found to improve the functioning of the
      pituitary-adrenal system. However, they did not contribute much to the positive
      changes in the pituitary-thyroid and other systems.

PMID- 1360739
TI  - [Natural coral used as a substitute for bone graft. Its role in the economics of
      blood in spinal surgery].

PMID- 1360740
TI  - Effects of l-stepholidine on tyrosine hydroxylase activity in rat corpus
      striatum.
AB  - l-Stepholidine (SPD) 2.5 and haloperidol (Hal) 1.0 mg.kg-1 ip increased rat
      striatal L-3,4-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenylacetic acid
      (DOPAC) accumulation induced by NSD 1015 (50 mg.kg-1, ip), a decarboxylase
      inhibitor. SPD (2.5 mg.kg-1, ip) did not alter but apomorphine (2.0 mg.kg-1, ip)
      decreased the dopamine (DA) content elevated by gamma-butyrolactone (GBL, 750
      mg.kg-1, ip) in the rat striatum. Ip injection of either SPD 5.0 or Hal 2.5 mg.kg
      1 after NSD 1015 50 mg.kg-1 or NSD 1015 plus GBL 750 mg.kg-1 also augmented
      tyrosine hydroxylase (TH) activity in the rat striatum. These results suggest
      that SPD produces an antagonistic effect on presynaptic DA receptors.

PMID- 1360741
TI  - Comparison of effects of tetrahydropalmatine enantiomers on firing activity of
      dopamine neurons in substantia nigra pars compacta.
AB  - Extracellular single unit recording techniques were used to elucidate the effects
      of enantiomers of tetrahydropalmatine (THP) on the firing activity of dopamine
      (DA) neurons in substantia nigra pars compacta (SNC). (-)-THP rapidly reversed
      the apomorphine (Apo)-induced inhibition of the SNC DA cell firing activity (ED50
      = 0.77, 0.52-1.14, mg.kg-1), while much larger doses of (+)-THP were required to
      reverse the Apo-induced inhibition (ED50 = 23, 15.2-34.7, mg.kg-1) and the
      maximal reversal caused by (+)-THP was 79 +/- 9% of the basal firing rate. In
      paralyzed rats, (-)-THP (0.5-16 mg.kg-1) significantly increased the spontaneous
      firing rate of SNC DA neurons dose-dependently, while (+)-THP did not until the
      dose reached 16 mg.kg-1. Pretreatment with (-)-THP 4 mg.kg-1 attenuated Apo
      induced inhibition of SNC DA cell firing rate, while (+)-THP 32 mg.kg-1 revealed
      a similar potency to block the Apo-induced inhibition. In addition, (+)-THP did
      not potentiate the effect caused by d-amphetamine (Amp) as some behavioral
      experiments have shown, but large dose of (+)-THP (32 mg.kg-1) blocked the Amp
      induced inhibition of SNC DA cell firing activity as (-)-THP (4 mg.kg-1) did.
      These results suggest that the interaction between D2 receptors and THP
      enantiomers has stereoselectivity and that (-)-THP is a D2 antagonist while (+)
      THP seems to be not.

PMID- 1360742
TI  - A 10-year follow-up study of tardive dyskinesia.
AB  - In a 10-year follow-up study of 44 patients with tardive dyskinesia (TD), the
      majority (22 or 50%) had no change in their TD severity, 9 (20%) had an
      improvement and 13 (30%) had a worsening of their TD. Little difference was noted
      in those patients whose medication was decreased (n = 12) and those whose
      medication remained unchanged (n = 32). Of the women, 26% showed improvement as
      compared with 11% of the men. Also, patients whose TD improved had lower present
      neuroleptic dose than those whose TD worsened. These two factors should be
      studied in larger patient cohorts.

PMID- 1360743
TI  - The effects of alcohol and benzodiazepines on the severity of ski accidents.
AB  - Urine samples from 402 victims of ski accidents were analyzed for the presence of
      benzodiazepines (BZD) and alcohol. Eighty-one (20%) samples were positive for
      alcohol; BZD were detected in 34 (8.5%) cases. Ten of the samples (2.5%) were
      found to be positive for both alcohol and BZD. Subjects who were positive for
      either alcohol or BZD or both were older than the other persons examined. The
      prevalence of alcohol was significantly higher among male accident victims. BZD
      intake could be demonstrated to have a significant influence on the severity of
      injuries. Besides an increased awareness of the need for skier education
      regarding drug use, heightened attention of medical caregivers is warranted to
      inform their patients about potential accident hazards in sport activities when
      BZD are prescribed.

PMID- 1360745
TI  - Molecular perspectives on the genetics of mosquitoes.

PMID- 1360744
TI  - Regulation of calcitonin gene expression by hypocalcemia, hypercalcemia, and
      vitamin D in the rat.
AB  - High calcium leads to the secretion of calcitonin, and the administration of 1,25
      dihydroxyvitamin D3 leads to a decreased transcription of the calcitonin gene. We
      now report the effect of chronic hypercalcemia, hypocalcemia, and vitamin D
      deficiency on calcitonin gene expression in vivo in the rat. Hypercalcemia was
      created by calcium infusions for 6 h, a high-calcium diet given to weanling rats
      for 3 weeks, and the transplantation of the Walker carcinosarcoma 256 cell line.
      Despite serum calcium as high as 22 mg/dl, there was no difference in calcitonin
      mRNA levels among these rats. The control genes studied, actin and somatostatin,
      which is specific for C cells in the thyroparathyroid tissue, also did not differ
      among the different groups of rats. Injected 1,25-(OH)2D3 decreased calcitonin
      mRNA levels at 6 h, as previously reported. Hypocalcemia, created by feeding
      diets deficient in calcium and vitamin D to weanling rats for 3 weeks, had no
      effect on calcitonin mRNA levels, in contrast to the large increases in PTH mRNA
      levels. These results demonstrate that calcitonin gene expression in vivo in the
      rat is regulated by administered 1,25-(OH)2D3 but not by changes in serum
      calcium.

PMID- 1360746
TI  - Tonsils: A clinically oriented update. 2nd International Symposium on Tonsils.
      Pavia, September 11-13, 1991.

PMID- 1360747
TI  - Autonomic nervous system in the tonsil.

PMID- 1360749
TI  - Production of monoclonal antibodies to rotavirus suitable for detection of
      rotavirus in stool samples by one-step EIA.
AB  - Two stable hybridoma cell clones producing high amounts of monoclonal antibodies
      (MAb) to rotavirus have been selected. The MAbs were shown to recognize different
      epitopes of the major inner capsid rotavirus protein VP 6. The two types of MAb
      in question cross-reacted with human and animal group A rotaviruses. Due to their
      high affinity and good binding capacity to microtiter plates a simultaneous EIA
      was developed for detection of rotavirus in stool samples. The sensitivity and
      specificity of MAb one-step EIA was compared with an approved polyclonal sandwich
      EIA by testing 1309 stool samples.

PMID- 1360750
TI  - Isolation and purification of HSV-1 specific transfer factor produced by HSV-1
      immunized goat leukocyte dialysate.
AB  - A herpes simplex virus type 1 (HSV-1)-specific transfer factor (TF), was
      separated and purified from the leukocyte dialysate of goats immunized with HSV-1
      using affinity chromatography on antigen-sorbent and reversed phase high
      performance liquid chromatography (RP-HPLC). The antigen-specific activities of
      the starting dialysate and the isolated TF component (s) were examined by 51Cr
      labelled leukocyte adherence inhibition (51Cr LAI) assay. The analytical
      hydrophobic interaction HPLC (HI-HPLC) and isoelectric focusing (IEF) techniques
      were employed to evaluate the purity and the isoelectric point (PI) of isolated
      TF component(s). The experiments provided a two-step procedure for purifying the
      TF material from the starting dialysate. It seems that the purified active TF
      component (PTFC) was specific for HSV-1. The specific PTFC activity was increased
      10,000-fold as compared with the activity of the dialysate. The active moiety
      appeared as a single band in the IEF gel as demonstrated by silver staining; it
      was hydrophilic and its PI was pH 4.48.

PMID- 1360748
TI  - Electrophysiological characterization of histamine receptor subtypes in sheep
      cardiac Purkinje fibers.
AB  - The histamine-receptor-subtype-mediated effects on action potentials of
      electrically driven and spontaneously active isolated sheep cardiac Purkinje
      fibers were investigated using H1- and H2-selective agonists and antagonists. In
      electrically stimulated Purkinje fibers, histamine (3 mumol/l) increased the
      action potential plateau height, decreased the action potential duration measured
      at a repolarization level of -60 mV and enhanced the pacemaker activity. These
      effects were abolished by the H2-selective antagonist cimetidine (30 mumol/l),
      but were not impaired by the H1-selective antagonist dimetindene (0.3 mumol/l).
      In spontaneously active Purkinje fibers, histamine (10 mumol/l) increased the
      spontaneous rate by 24%, the slope of diastolic depolarization by 45% and
      shortened the duration of the diastole by 32% of the respective control
      measurements. These effects were blocked by 30 mumol/l cimetidine, but remained
      unchanged in the presence of 0.3 mumol/l dimetindene. Concentration-response
      curves of histamine were shifted to the right by approximately 2 logarithmic
      units in the presence of 30 mumol/l cimetidine, but were not influenced in the
      presence of 0.3 mumol/l dimetindene. The H2-selective agonist impromidine (0.001
      0.3 mumol/l) had similar actions as histamine on spontaneously active Purkinje
      fibers, while the H1-selective agonist 2-(2-pyridyl-)ethylamine was ineffective.
      It is concluded that the pronounced stimulatory action of histamine on
      spontaneous activity in sheep cardiac Purkinje fibers is exclusively mediated by
      H2 receptors.

PMID- 1360751
TI  - Chemical characterization of the purified component of specific transfer factor
      in the leukocyte dialysates from HSV-1 immunized goats.
AB  - The chemical characterization of the purified component responsible for HSV-1
      specific transfer factor activity (PTFC) by high resolution analytical methods
      was performed. PTFC had a molecular weight of 6,000 dalton by the size-exclusion
      HPLC analysis; it showed a marked UV-absorbance spot at 254 nm and a fluorescent
      spot at 366 nm on the thin-layer plate by thin-layer chromatography which spots
      coincided at the same place of the plate. The amino acid composition and
      sequencing analyses showed that PTFC consisted of at least twelve different amino
      acids, but the amino acid sequence could not be determined. The combined results
      indicate that PTFC is a compound with a molecular weight of 6,000 dalton,
      composed of peptide and nucleotide-like material. The peptide is rich in aspartic
      acid and its N-terminal end may be blocked.

PMID- 1360752
TI  - Comparison of two defective hepatitis A virus strains adapted to cell cultures.
AB  - The replication of two defective hepatitis A virus strains in cell culture was
      examined. The w.t. HAS-15 strain growing in FRhK-4 cells produced infectious
      icosahedral virions 27 nm in size as well as round shaped particles with lipids
      attached to their surface. The morphogenesis of HAV was membrane-dependent and
      the detected particles were in various degree of maturation. The MBB 11/5 strain
      growing in PLC/PRF/5 cells produced mainly noninfectious empty procapsids without
      RNA genome. The translation of viral proteins was uninhibited in both strains.
      The reason for restricted replication competence of both strains seemed to be
      different. In HAS-15, highly efficient encapsidation of the progeny RNA positive
      strand lowered the formation of replicative intermediate forms. In MBB 11/5,
      nearly exclusive empty procapsid production gave evidence for the failure of the
      VPg primer protein attachment to viral RNA. Changes in the efficacy of viral
      genome replication were a result of the adaptation of HAV to propagation in
      vitro.

PMID- 1360753
TI  - Binding rate of rabies virus to alpha interferon primed mouse neuroblastoma
      cells.
AB  - Mouse neuroblastoma cells (MNA) were primed with 20 I.U. of alpha interferon (Mu
      IFN-alpha) prior to exposure to the Challenge Virus Standard strain of rabies
      virus (CVS). Saturation of CVS receptor sites occurred when 0.71 microgram of 3H
      CVS protein bound to 20,000 MNA cells. After 180 min incubation time, the amount
      of viral protein attributed to specific binding was estimated to be 0.45
      microgram. Mu IFN-alpha treatment of MAN cells did not increase the number of
      specific cell receptor sites to CVS but it did significantly increase the rate
      that CVS was able to bind to cell receptors. The amount of time required to reach
      saturation of MNA cell receptors to CVS decreased from 120 min in untreated cells
      to 30 min in Mu IFN-alpha primed MNA cells. Although treatment with Mu IFN-alpha
      increased the binding rate of rabies virus to MNA cells, the virus was unable to
      complete a productive infection 48 hrs after the Mu IFN-alpha was removed.

PMID- 1360754
TI  - Detection of tick-borne encephalitis virus in ixodid ticks collected in natural
      foci by time-resolved fluoroimmunoassay.
AB  - Time-resolved fluoroimmunoassay (TR-FIA) was used for the first time for
      evaluation of infestation of ixodid ticks with tick-borne encephalitis virus.
      Comparison of TR-FIA results with those obtained in enzyme immunoassay and by
      virus isolation confirmed the high efficacy of the method in question. Positive
      results of TR-FIA coincided with the data of virus isolation in 83.6% cases, the
      level of false-negative results did not exceed 1.2%, the overall time consumption
      amounted to about 1.2 hr.

PMID- 1360755
TI  - Immunoenhancement and suppression induced by adenovirus in chicken.
AB  - Chickens injected intravenously (i.v.) with human adenovirus type 6 (Ad6) reveal
      a 2-17-fold increase in the number of plaque-forming cells producing antibody
      (Ab) against sheep red blood cells (SRBC) 2-6 days after virus infection.
      Further, polyclonal B-cell activation has been demonstrated by the quantitation
      of immunoglobulin-producing cells (IgPC) and cells producing immunoglobulin (Ig)
      of IgM isotype (IgPC mu) in the spleen of chicken inoculated with Ad6. Ad6
      infection in chicken results in immunosuppression against SRBC when this
      unrelated antigen is given after virus infection. It seems that coincidence
      occurs between the B-cell mitogenic activation and the immunosuppression caused
      by Ad6, as the most pronounced change in both activities appears on the fourth
      day following virus infection. These findings suggest that the B-cell
      mitogenicity of the virus contributes to the impairment of the humoral immune
      response to SRBC.

PMID- 1360756
TI  - Two-way cross-protection between West Nile and Japanese encephalitis viruses in
      bonnet macaques.
AB  - Cross-protection between Japanese encephalitis (JE) and West Nile (WN) viruses
      was tested in bonnet macaques (Macaca radiata) immunized either with JE virus
      (JEV) or WN virus (WNV). JEV immunized monkeys were challenged by intranasal
      (i.n.) route with WNV and vice versa. Four control unimmunized monkeys were
      similarly infected either with WNV or JEV. Two of three control monkeys infected
      with WNV, developed paralysis followed by death. Virus was recovered from the
      central nervous system (CNS) of the both dead control monkeys and the
      histopathological examination of CNS revealed changes suggestive of viral
      encephalitis. The control monkey infected with JEV developed encephalitis and the
      virus was recovered from the blood and CNS. All the 3 JEV-immunized monkeys
      withstood WNV challenge, whereas only 2 of the 5 WNV immunized monkeys withstood
      the challenge with JEV. Out of 3 WNV-immunized monkeys surviving challenge with
      JEV, 2 revealed symptoms suggestive of mild encephalitis followed by complete
      recovery. The third monkey died on the 60th day post-infection (p.i.) without any
      symptoms and virus was recovered only from the olfactory lobe. These studies
      indicate that the immunization with JEV protects the bonnet macaques against WNV,
      whereas the WNV immunization only reduces the severity of the disease due to JEV.

PMID- 1360757
TI  - Effect of acyclovir on selected immune functions.
AB  - The toxicity of acyclovir (ACV) produced by Lachema, Brno was compared with that
      of Zovirax, Wellcome. The in vitro suppressive effect of both substances was
      found equal and concentration dependent. The primary humoral antibody response
      was more sensitive to ACV than the cellular (blast transformation) response.
      However, spleen cells of drug-treated mice (either with the domestic compounds or
      Wellcome origin) differed neither in blast transformation test nor in the
      secretory antibody response. None of the drugs when given in adequate therapeutic
      dose did significantly influence the cell mediated response or antibody formation
      by spleen cells. Summing up, the acute immunotoxicity of both compounds was low;
      in this respect acyclovir Lachema did not differ from Zovirax Wellcome.

PMID- 1360758
TI  - Serological diagnosis of parainfluenza virus infections: verification of the
      sensitivity and specificity of the haemagglutination-inhibition (HI), complement
      fixation (CF), immunofluorescence (IFA) tests and enzyme immunoassay (ELISA).
AB  - Using four serological tests paired sera were examined of 117 patients with acute
      respiratory diseases, in whom parainfluenza viruses (PIV) infection was
      demonstrated by virus isolation, and of 41 patients with typical clinical mumps
      symptoms. Comparative analysis showed the high sensitivity of IFA and ELISA. A
      significant rise of antibodies in convalescent sera with homologous antigen of
      PIV was found in nearly 100 percent of cases. Only the sera of youngest children
      with high titres of persisting maternal antibodies remained without
      seroconversion. Cross heterologous antibody responses could be found by means of
      ELISA in 45% and by IFA in 10%, of patients who in the past experienced infection
      with one or more PIV or mumps virus--apart from homologous antibody reaction. HI
      and CF test proved to be less sensitive for detection of postinfections
      antibodies, especially in primoinfections with PIV types 1 and 2.

PMID- 1360759
TI  - Pretreatment of the host cell with 1-(S)-(3-hydroxy-2
      phosphonylmethoxypropyl)cytosine (HPMPC) is sufficient for its antiviral effect.
AB  - 1-(S)-(3-Hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) inhibits efficiently
      human cytomegalovirus (HCMV) replication. The drug exhibited marked antiviral
      effect in vitro not only at single application after virus adsorption, but also
      if given 48 hr post-infection. The inhibition of HCMV replication by HPMPC
      occurred after mere pretreatment of the host cells with the drug followed by its
      removal from the medium before virus infection. No free or host cell bound
      infectious virus was detected in the drug pretreated (1.5 micrograms/ml) virus
      infected cells. This effect was drug concentration dependent.

PMID- 1360760
TI  - Detection of influenza B virus in throat swabs using the polymerase chain
      reaction.
AB  - An assay protocol based on exploiting the polymerase chain reaction (PCR) for the
      direct detection of influenza B virus in throat swabs is described. By the use of
      PCR with nested primers, it was possible to detect the virus in throat swabs.
      Dilution experiments showed that as little as 1 plaque forming unit of virus was
      sufficient for detecting the HA gene by the PCR. All throat swab samples from
      which influenza B virus had been isolated by conventional methods were also
      positive by the PCR method.

PMID- 1360761
TI  - Detection of viral DNA polymerase activity in salmon tumour tissue induced by
      herpes virus, Oncorhynchus masou virus.
AB  - DNA polymerase activities were surveyed in tumour tissue and normal tissue of
      cherry salmon (Oncorhynchus masou). High activity of DNA polymerase alpha was
      detected in the tumour tissue but not in the normal tissue. This indicates that
      the tumour cells replicate prosperously. Viral DNA polymerase activity was
      detected only in the tumour tissue, indicating that Oncorhynchus masou virus
      (OMV) DNA should replicate there. DNA polymerase beta activity was of same level
      in both tissues. This is the first evidence that herpesvirus DNA polymerase was
      detected in tumour tissue in association with herpesvirus.

PMID- 1360762
TI  - Experimental infection of domestic cats by cowpox virus.
AB  - Infection of young domestic cats by cowpox virus isolated from sick rodents
      (family Muridae) revealed their high susceptibility to the virus; a severe
      disease with 100% lethality developed after oral inoculation as well as upon skin
      scarification. The disease in dermally infected animals was accompanied by
      eruptions on the site of inoculation. High concentration of the virus was
      detected in lungs of animals infected by either of inoculation routes. The data
      testify the possible participation of domestic cats as intermediate hosts in the
      circulation of cowpox virus.

PMID- 1360763
TI  - Possible use of matrix protein obtained by cloning in E. coli in the serological
      diagnosis of type A influenza.

PMID- 1360764
TI  - Takayasu's arteritis as a cause of orofacial pain.

PMID- 1360765
TI  - Urinary incontinence in the elderly: pharmacologic therapies.
AB  - Treatment of acute urinary incontinence should be directed toward the underlying
      cause, such as infection, medication side effect, atrophic vaginitis, anxiety,
      depression and restricted mobility. Pharmacologic treatment depends on
      identification of one of the four subtypes of chronic urinary incontinence:
      stress, urge, overflow or mixed. Stress incontinence responds to alpha-adrenergic
      agents, which increase sphincter tone. Urge incontinence is the most common type
      of incontinence in the elderly; it can be treated with anticholinergic agents,
      smooth muscle relaxants, estrogen replacement therapy in women and, possibly,
      calcium antagonists. Overflow incontinence is caused by neurologic deficits, such
      as diabetes, or outflow obstruction, such as from prostatic enlargement, urethral
      stricture and tumors. Anticholinergic agents and alpha-adrenergic agents should
      be considered only after existing outflow obstruction is surgically corrected or
      intermittent catheterization is unsuccessful.

PMID- 1360766
TI  - Update on drug therapy for HIV and related infections in adults.
AB  - Antiretroviral therapy with zidovudine is indicated in patients with CD4 cell
      counts below 500 per mm3 (500 x 10(6) per L). Patients intolerant of zidovudine
      and those with advanced human immunodeficiency virus infection may benefit from
      newer antiretroviral agents, such as didanosine (ddl) or zalcitabine (ddC).
      Prophylactic therapy for Pneumocystis carinii pneumonia is indicated in patients
      with CD4 cell counts below 200 per mm3 (200 x 10(6) per L), in patients with CD4
      cell counts less than 20 percent of the total lymphocytes and in patients with a
      prior history of P. carinii infection. In addition, prophylaxis is often
      initiated if thrush is present, even when CD4 cell counts are above 200.
      Trimethoprim-sulfamethoxazole is the drug of choice for Pneumocystis prophylaxis;
      aerosolized pentamidine is reserved for patients unable to tolerate trimethoprim
      sulfamethoxazole. Oral candidiasis is treated with nystatin suspension,
      clotrimazole troches, ketoconazole or fluconazole, with fluconazole used for
      resistant or more invasive infection. Finally, acyclovir is used to treat herpes
      zoster or herpes simplex virus infection.

PMID- 1360767
TI  - International classification of osteochondrodysplasias. International Working
      Group on Constitutional Diseases of Bone.

PMID- 1360768
TI  - Further evidence for dominant inheritance at the chromosome 15q11-13 locus in
      familial Angelman syndrome.
AB  - Eleven patients with Angelman syndrome (AS) and their parents from 5 families
      have been studied with high resolution chromosome analysis and molecular probes
      from region 15q11-13 in an attempt to elucidate the mode of inheritance in
      familial AS. No deletions were detected. All families were informative with a
      combination of different short arm cytogenetic markers. All sets of sibs
      inherited the same maternal chromosome 15, but in 3 families sibs inherited
      different paternal 15s. Analysis of 6 polymorphic DNA markers supported the
      conclusion that AS sibs inherit the same maternal 15, but often different
      paternal 15s. These data make autosomal recessive inheritance at a 15q11-13 locus
      very unlikely and support the hypothesis that familial AS is due to maternal
      transmission of a mutation within 15q11-13.

PMID- 1360769
TI  - Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome.
AB  - Velo-cardio-facial syndrome (VCFS), an autosomal dominant disorder, is
      characterized by cleft palate, cardiac defects, learning disabilities and a
      typical facial appearance. Less frequently, VCFS patients have manifestations of
      the DiGeorge complex (DGC) including hypocalcemia, hypoplastic or absent lymphoid
      tissue and T-cell deficiency suggesting that these 2 conditions share a common
      pathogenesis. Here, we report the results of cytogenetic and molecular studies of
      15 VCFS patients. High-resolution banding techniques detected an interstitial
      deletion of 22q11.21-q11.23 in 3 patients. The remaining 12 patients had
      apparently normal chromosomes. Molecular analysis with probes from the DiGeorge
      Chromosome Region (DGCR) within 22q11 detected DNA deletions in 14 of 15
      patients. In 2 families, deletions were detected in the affected parent as well
      as the propositus suggesting that the autosomal dominant transmission of VCFS is
      due to segregation of a deletion. Deletions of the same loci previously shown to
      be deleted in patients with DGC explains the overlapping phenotype of VCFS and
      the DGC and supports the hypothesis that the cause of these two disorders is the
      same.

PMID- 1360770
TI  - Onset of action and duration of effect of formoterol and salmeterol compared to
      salbutamol in isolated guinea pig trachea with or without epithelium.
AB  - Formoterol and salmeterol are 2 newly developed beta 2-adrenoceptor agonists for
      inhalation with prolonged duration of effect compared with currently available
      beta 2-agonists. The clinical duration of effect has been suggested to be
      correlated to a decreased washability in vitro, i.e. decreased effect due to
      continuous washing of the organ bath. In this study we compared the washability
      and the onset of the relaxatory effect of formoterol (0.01 microM), salmeterol
      (0.05 microM) and salbutamol (0.1 microM) in isolated guinea pig trachea
      contracted with carbachol (0.1 microM). We also evaluated a possible influence of
      the epithelium on onset of action and/or duration of effect. A significant
      relaxatory effect of formoterol and salmeterol remained after washing, whereas no
      effect of salbutamol remained. We also found a rapid onset of action for both
      salbutamol and formoterol, but a significantly slower onset for salmeterol. Both
      the washability and the onset of action were found to be independent of the
      presence of the epithelium.

PMID- 1360771
TI  - Amplified assay of alkaline phosphatase using flavin-adenine dinucleotide
      phosphate as substrate.
AB  - A simple to use, robust, quantitative, and extremely sensitive colorimetric assay
      for alkaline phosphatase (EC 3.1.3.1), designed to be used as a detection system
      in diagnostic assays employing antibodies or gene probes, is described. This
      technology is based on the novel principle of prosthetogenesis, according to
      which a purpose-designed substrate (a prosthetogen) for a primary analyte-linked
      enzyme label is hydrolyzed to produce a prosthetic group for a detector enzyme
      system. The prosthetogen employed here is a derivative of FAD which is
      phosphorylated at the 3'-position of the ribose ring (FADP), the label enzyme is
      alkaline phosphatase, and the detector is a D-amino-acid oxidase/horseradish
      peroxidase-coupled system. Essentially each turnover of every molecule of
      alkaline phosphatase produces a molecule of D-amino-acid oxidase for detection.
      Thus enormous amplification of the initial signal is achieved in short time
      periods because of the relatively high turnover number of alkaline phosphatase
      for FADP. The system can be formatted as a stable, preformed, freeze-dried
      preparation containing all analytical components, which is reconstituted simply
      by addition of buffer solution. This methodology can quantitate less than 0.1
      amol of alkaline phosphatase in 30 min at 25 degrees C using microtiter plates.

PMID- 1360772
TI  - Immunocytochemical and in situ hybridization evidence for the coexistence of GABA
      and tyrosine hydroxylase in the rat locus ceruleus.
AB  - We have demonstrated the coexistence of GABA-like and tyrosine hydroxylase-like
      immunoreactivities (GABA-LI and TH-LI, respectively) in the same neurons of the
      rat locus ceruleus (LC). The profiles of these cells were labeled by alternately
      immunostaining adjacent sections for GABA-LI or TH-LI by the avidin-biotin
      peroxidase complex method or the peroxidase-anti-peroxidase method after
      perfusion (either Zamboni's fixative or PPG), and observation at light and
      electron microscopic levels. For light microscopy, pairs of adjacent sections of
      more than 590 (Zamboni's) and 260 (PPG), and for electron microscopy, 40
      ultrathin sections cut from adjacent semithin plastic sections (Zamboni's), were
      examined. GABA-LI was found in 80% (1,309/1,642 in total) of small and medium
      sized neurons, uniformly scattered throughout the LC. Observations unequivocally
      show that the majority of GABA-ergic neurons are also noradrenergic. Several
      neurons are neither noradrenergic nor GABA-ergic, while other noradrenergic
      neurons do not show GABA-LI. It is shown that astrocytes, but not
      oligodendrocytes, contain GABA. In situ hybridization using a probe DNA fragment
      of the glutamic acid decarboxylase (GAD) cDNA, amplified by the polymerase chain
      reaction, detected GAD mRNA signals in many neurons throughout the LC, supporting
      the presence of a GAD/GABA system in the LC. Multiple "classical" transmitters,
      including GABA, serotonin, and noradrenaline, coexist in many LC neurons and may
      contribute to its widely diverging projections throughout the entire CNS.

PMID- 1360773
TI  - Role of long-acting beta 2 agonists in asthma.

PMID- 1360774
TI  - Sustained improvement in asthma with long-term use of formoterol fumarate.
AB  - Inhaled formoterol fumarate, a long acting beta 2 agonist, produces
      bronchodilatation that is sustained for approximately 12 hours. To determine
      whether such bronchodilator effects are maintained and asthma control sustained
      during chronic administration, we monitored airflow indices and clinical control
      in 112 asthmatic patients who self administered formoterol twice daily for
      periods ranging from 9 to 12 months. Subjects were recruited immediately
      following completion of a 3-month double-blind comparison of formoterol, 12
      micrograms, bid versus salbutamol, 200 micrograms, qid. Assessments were
      conducted at baseline, 3, 6, and 9 months, where baseline represents the final
      visit of the 3-month comparative study. Patients were asked to complete diary
      cards and twice daily PEFR for a 2-week period before each assessment. Throughout
      the follow-up study, there was no indication of worsening of asthma control or
      deteriorating lung function. For the patients who continued to receive
      formoterol, the previous improvement in asthma control and lung function was
      maintained at the level reached in the 3-month study. There was an improvement in
      flow rates and asthma symptoms in the group switched from salbutamol to
      formoterol by the first clinic visit. This improvement in asthma control and lung
      function was maintained over the subsequent 6 months. Formoterol was well
      tolerated during the study period. We conclude that prolonged use of formoterol
      fumarate twice daily results in sustained improvement in symptoms and flow rates
      in asthma with no evidence of tachyphylaxis.

PMID- 1360775
TI  - Detection of beta-blocker use in people with asthma.
AB  - Although there have been numerous reports of adverse outcomes for people with
      asthma who are placed on beta-blockers, there has been no description of how
      often people with asthma receive prescriptions for beta-blockers. Despite the
      fact that pharmacy claims are available and can be used for clinical evaluation,
      there has been no description of a practical surveillance or warning system to
      recognize and reduce the rate of beta-blocker use in people with asthma. This
      study used administrative claims data to estimate the prevalence of patients with
      asthma who also had prescriptions for beta-blockers. Chart audit was used to
      supplement our understanding of the causes of the problem and its consequences.
      In the calendar year 1989, in a large midwestern group practice that contracts
      with a single health maintenance organization (HMO), 3,170 HMO patients presumed
      to have asthma were identified. Of those 3,170 patients, 44 or 1.4% also had
      filled prescriptions for beta-blockers. The occurrence of beta-blocker use varied
      by age group: from less than 1% in patients below 30 years of age, rising to 8.9%
      in patients aged 60 to 69. Two of the patients with asthma who had prescriptions
      for beta-blockers were hospitalized for asthma in the study period. In 61% of the
      cases, different physicians managed the asthma care from those who prescribed the
      beta-blockers. In the remaining 39%, one physician was responsible for both the
      asthma care and beta-blocker prescription. We conclude prescribing beta-blockers
      for individuals with asthma is not uncommon. Current systems of administrative
      claims data permit the development of warning systems to help avert adverse
      outcomes.

PMID- 1360776
TI  - Oxatomide modifies methacholine- and exercise-induced bronchoconstriction in
      asthmatic children.
AB  - Oxatomide is a potent inhibitor of both the release and effects of allergic
      mediators and is similar to calcium antagonists in chemical structure. It
      prevents histamine release by inhibiting not only the increase in calcium intake,
      but also intracellular calcium release. We investigated its effect on
      methacholine-induced and exercise-induced bronchoconstriction in asthmatic
      children. Methacholine challenges were performed after oral administration of
      0.88 mg/kg oxatomide or placebo in nine asthmatic children in a double-blind
      placebo-controlled study. Respiratory thresholds were improved in seven patients
      and log PC20 in the oxatomide group (6.65 +/- 1.34 micrograms/mL) was
      significantly higher than that in the placebo group (5.74 +/- 1.04 micrograms/mL)
      (P < .05). Exercise challenges were performed after oral administration of 1.5
      mg/kg oxatomide or placebo in eight asthmatic children in a double-blind placebo
      controlled study. Oxatomide produced acute bronchodilatation with 6.1%
      improvement on an average in FEV1. The mean maximal % fall obtained by oxatomide
      was 13.5%, while that by placebo was 22% (P < .05). These results indicate that
      oxatomide reduces nonspecific bronchial hyperresponsiveness.

PMID- 1360777
TI  - Polymorphisms of a scrapie-associated fibril protein (PrP) gene and their
      association with susceptibility to experimentally induced scrapie in Cheviot
      sheep in the United States.
AB  - The duration of the incubation period for scrapie, a fatal transmissible
      neurodegenerative disorder of sheep and goats, is mainly determined by the Sip
      gene, which has 2 alleles (sA--susceptible and pA--resistant). A diagnostic test
      is not available to detect scrapie in live animals. We analyzed genomic DNA
      extracted from frozen sheep brains collected from Cheviot sheep of the United
      States that had been inoculated with the SSBP/1 scrapie inoculum. Digestion of
      the DNA with EcoRI or HindIII followed by the addition of a scrapie-associated
      fibril protein (PrP)-specific marker probe, yielded fragments of 6.8 (e1) and 4.0
      (e3) kb, or 5.0 (h1) and 3.4 (h2) kb, respectively. Fragments e1 and h2 were
      associated with the histopathologic diagnosis of scrapie, and fragments e3 and h1
      were associated with survival. A valine/alanine polymorphism within the PrP
      coding region that resulted in a BspHI site was further used to determine the
      genotype of these Cheviot sheep. Digestion of polymerase chain reaction fragments
      with BspHI resulted in an undigested fragment b- (0.840 kb), digested fragments
      b+ (0.460 and 0.380 kb), or both types of fragments. Survival time of b+/b+
      homozygous sheep was significantly (P < 0.01) shorter (218 +/- 26.0 days) than
      survival time for b-/b- sheep (> 700 days after inoculation). Results indicated
      that b+ and b- are markers for the Sip sA and pA alleles, respectively. The
      intermediate duration of the incubation period for heterozygous sheep (b+/b-;
      342.9 +/- 25.3 days) indicated that the Sip sA allele is expressed codominantly
      to the Sip pA allele.

PMID- 1360779
TI  - Beta 2-agonists and corticosteroids: new developments and controversies. Report
      of a meeting in November 1990.

PMID- 1360778
TI  - Serum secretory leukoprotease inhibitor levels to diagnose pneumonia in the
      elderly.
AB  - In pneumonia in the elderly, one occasionally encounters difficulties in
      evaluation with respect to both clinical observation and treatment. Thus a simple
      serum indicator is indicated. We measured secretory leukoprotease inhibitor
      (SLPI) concentrations in sera to see whether this can provide a useful indicator
      for pneumonia, especially in the elderly. Serum samples from patients over 65 yr
      of age, with (n = 54) or without (n = 87) pneumonia, and from healthy, young (n =
      16) and aged (n = 188) control subjects were assayed using ELISA for human SLPI.
      Comparisons were made between groups with clinical diagnoses of either definite
      or probable pneumonia and among cases with various other respiratory diseases,
      including bronchial asthma, chronic obstructive pulmonary disease, and lung
      cancer. The mean SLPI concentration in patients with pneumonia was significantly
      higher than in patients without pneumonia or in healthy controls. The data
      suggest that the measurement of SLPI can provide a useful indicator for pneumonia
      to be used in clinical evaluation.

PMID- 1360780
TI  - Neuro-Immuno-Physiology of the Gastrointestinal Mucosa: Implications for
      Inflammatory Diseases. Conference. Tucson, Arizona, January 24-28, 1992.

PMID- 1360781
TI  - Neuroimmune modulation of epithelial function. An overview.

PMID- 1360782
TI  - Leukocyte adhesion and emigration in inflammation.

PMID- 1360783
TI  - [Treatment of recurrent ulcers after parietal cell vagotomy. Analysis of 18
      cases].
AB  - One hundred and twenty seven patients had a follow-up of more than 4 years after
      parietal cell vagotomy for duodenal, pyloric or prepyloric ulcer. The recurrence
      rate is 15.8% (20 on 127). Eighteen patients who have recurred, had a follow-up
      of 2 years or more after treatment of the recurrent disease. Ten patients had a
      early recurrence (within 2 years); eight had a late one (more than 2 years). One
      patient had been operated as an emergency for perforation. Seventeen patients had
      first received a medical treatment. This treatment was sufficient for 10 out of
      17. Seven patients were reoperated (3 partial gastrectomy), 4 partial gastrotomy
      associated with truncal vagotomy. Seven out of the 10 early recurrences was
      reoperated and only one of the 8 late recurrences was reoperated. The early
      recurrences seem to be more serious that the late ones. Medical treatment is
      always prescribed as first line therapy and a partial gastrectomy alone or with
      vagotomy is necessary in unsuccessful cases.

PMID- 1360784
TI  - Results of surgery in primary hyperparathyroidism.
AB  - In a prospective study 92 consecutive patients with biochemically proved primary
      hyperparathyroidism underwent initial neck exploration at Oulu University
      Hospital. The incidence of multiglandular disease was 34%. 23 patients (25%)
      underwent a simultaneous thyroidectomy. The cure rate after initial exploration
      was 91.3%, ectopic parathyroid glands and multiglandular disease being the most
      common causes of failure. Simultaneous thyroidectomy increased somewhat but not
      significantly the complication risk. There was a slight tendency for serum
      calcium concentrations to increase during the mean follow-up of 2.3 +/- 1.5
      years. Four patients with persistent hypercalcaemia underwent a successful
      reoperation during that time. Thus the overall cure rate was 95.6%, but 5.4% of
      the patients required permanent medication for hypocalcaemia. We conclude that
      the most common causes for failed initial exploration were ectopic parathyroid
      glands and multiglandular disease. The incidence of multiglandular disease was
      unusually high in this series. Because simultaneous thyroidectomy increased
      somewhat the complication risk of initial neck exploration, the indications for
      this additional procedure should be carefully considered. The results of
      parathyroid surgery were good and dependent on how many patients underwent
      reoperation during the follow-up. A consequence of tendency for serum calcium
      concentrations to increase during the follow-up could be that a definite cure
      cannot always be attained in cases of primary hyperparathyroidism.

PMID- 1360785
TI  - Overview of principles and current uses of DNA probes in clinical and laboratory
      medicine.
AB  - Fundamental considerations of deoxyribonucleic acid (DNA) probe hybridization
      reaction including concept of stringency is reviewed. Restriction fragment length
      polymorphism (RFLP) and its detection using DNA probes are discussed together
      with the importance of RFLP in genetic linkage analysis. Methodological
      considerations, such as limitations in sample preparation and improvements
      effected in techniques, cloning DNA, and labelling of DNA probes, are addressed.
      Principles of hybridization technology and blotting techniques are reviewed.
      Amplification of DNA by the polymerase chain reaction (PCR), labelling with PCR,
      detection of PCR products and separation procedures prior to use of PCR are
      discussed. Other amplification methods and in-situ hybridization (ISH) procedures
      are reviewed. Selected current applications of DNA probes in the area of
      infectious diseases, genetic diseases, HLA typing, paternity and forensic testing
      are briefly discussed. Emphasis is placed on the use of DNA probes in the area of
      oncology. Background on activation of proto oncogene, loss of tumor suppressor
      genes, chromosomal translocation, and chromosome analysis are provided for
      understanding DNA probe assays for ph1 positive leukemias and applications of
      Interphase cytogenetic technique in oncology. Finally, analytical strategies for
      detection of tumor suppressor genes are addressed.

PMID- 1360786
TI  - Nigral damage and dopaminergic hypofunction in mesencephalon-immunized guinea
      pigs.
AB  - To support a potential role for immune mechanisms in the destruction of
      substantia nigra (SN) neurons, guinea pigs were immunized with bovine
      mesencephalon containing SN neurons. After immunization no clinical signs of
      basal ganglia dysfunction appeared. However, pathological examination revealed
      evidence of neuronal damage in the SN in 8 of 17 guinea pigs immunized with
      bovine mesencephalon. No nigral pathology was noted in animals immunized with
      spinal cord gray matter or Freund's adjuvant alone. Accompanying the SN damage in
      mesencephalon-immunized guinea pigs was a 25% decrease in tyrosine hydroxylase
      activity in the SN and a 27% decrease in dopamine content in the striatum.
      Deposits of IgG were detected by immunohistochemical techniques in sections of SN
      from mesencephalon-immunized guinea pigs and in sections of human SN after
      exposure to serum from mesencephalon-immunized guinea pigs. These data document
      the antigenicity of SN and suggest the possibility that immune mechanisms can
      contribute to basal ganglia pathology.

PMID- 1360787
TI  - Paternal uniparental disomy of chromosome 15 in a child with Angelman syndrome.
AB  - Angelman and Prader-Willi syndromes are clinically distinct neurobehavioral
      disorders most commonly resulting from large deletions of chromosome 15q11-q13.
      The deletions arise differentially during maternal or paternal gametogenesis,
      respectively. A subgroup of patients with either syndrome have no apparent
      deletion, and because many such patients with Prader-Willi syndrome display
      inheritance of two copies of chromosome 15 from the mother only (uniparental
      disomy; UPD), we suggested that paternal UPD might be found in patients with
      Angelman syndrome. We report here clinical, cytogenetic, and molecular evidence
      on the 1 patient with paternal UPD for chromosome 15 who was found in our study
      population. This represents, to our knowledge, the first patient with paternal
      UPD to be studied with DNA probes from the chromosome 15q11-q13 critical region.
      In contrast to our findings for patients with Prader-Willi syndrome, in which
      maternal UPD was common, our data demonstrate that paternal UPD is infrequent in
      patients with Angelman syndrome.

PMID- 1360788
TI  - [The 7th Mediterranean Congress on Chemotherapy].

PMID- 1360789
TI  - Number and DNA content of hypertrophic spermatogonia in normal and cryptorchid
      human testes.
AB  - The number and the DNA content of hypertrophic spermatogonia were studied in
      normal and cryptorchid testes. The number of hypertrophic spermatogonia in
      cryptorchid testes is higher than in control testes at the same age. This finding
      suggests alterations in the spermatogonia of cryptorchid males. The results show
      a polyploid DNA content in more than 80% of hypertrophic spermatogonia in both
      normal and cryptorchid testes. There were hypertrophic spermatogonia with a DNA
      content between 2c and 4c (0.5%) and between 4c and 8c (9%). These spermatogonia
      might be cells in the S phase of the cell cycle.

PMID- 1360790
TI  - Alpha- and beta-adrenoceptor cross-talk in the regulation of glycogenolysis in
      dog and guinea-pig liver.
AB  - The dog liver glycogenolytic response to isoprenaline (EC50 = 3 x 10(-9) M) was
      selectively blocked by 10(-5) M of practolol, but not by butoxamine. In contrast,
      the glycogenolytic response to isoprenaline (EC50 = 3 x 10(-7) M) was inhibited
      by 10(-6) M of butoxamine, but not by practolol, in the guinea-pig liver. This
      suggests that, in the dog, the isoprenaline response is dominated by beta 1
      adrenoceptors, while in the guinea-pig beta 2-receptors control such response.
      Glucose release from dog and guinea-pig liver slices was also stimulated by
      amidephrine (EC50 = 10(-6) M in the dog and 4 x 10(-5) M in the guinea-pig). Both
      prazosin and yohimbine blocked this response. The effectiveness of clonidine as a
      glucose-mobilizing agent could only be established in the dog liver. Prazosin
      showed greater activity than yohimbine in antagonizing the response to both
      agonists. In the dog, low concentrations of alpha-adrenoceptor agonists (10(-9)
      M), that failed to modify the basal glucose release per se, selectively depressed
      the isoprenaline response. Prazosin, but not yohimbine, reversed this inhibitory
      effect. It is concluded that glucose release from the dog liver is regulated by
      two opposite mechanisms that seem to be associated to alpha 1-adrenoceptors
      (inhibitory) and to beta 1-adrenoceptors (stimulatory).

PMID- 1360791
TI  - Coexistence of presynaptic beta 1- and beta 2-adrenoceptors in splenic strips
      from young rats and betaxolol-induced beta 1-stereoselective antagonism.
AB  - The pharmacological properties of facilitatory presynaptic beta-adrenoceptors
      were characterized using three kinds of beta-agonists and antagonists in
      superfused strips from young Sprague-Dawley rats, loaded with [3H]noradrenaline.
      Isoproterenol (10(-9) M to 10(-7) M) concentration-dependently facilitated [3H]
      release evoked by transmural field stimulation at 5 Hz. Salbutamol (10(-8) M and
      10(-7) M) and prenalterol (10(-8) M to 10(-6) M) also facilitated the stimulation
      evoked [3H] release. Pretreatment with ICI 118,551 (10(-6) M) completely
      antagonized the concentration-facilitation curve for isoproterenol (10(-9) M to
      10(-7) M). Atenolol (10(-6) M) antagonized only the isoproterenol (10(-9) M)
      induced facilitation. dl-Betaxolol (10(-6) M) antagonized the isoproterenol (10(
      9) M and 10(-8) M)-induced facilitation and the antagonistic action for
      isoproterenol (10(-8) M) was more marked than that of atenolol, whereas the same
      concentration of d-betaxolol produced no antagonism. Thus, presynaptic beta 1-
      and beta 2-adrenoceptors coexist on noradrenergic neurons innervating splenic
      strips of young rats. Betaxolol is a useful tool to characterize presynaptic beta
      1-adrenoceptors.

PMID- 1360792
TI  - 6-[N,S-dimethyl-N'-cyanothioureidomethyl]-6,11-dihydro-5H- dibenz[b,e]azepine
      hydrochloride (Fran 12): a histamine and 5-hydroxytryptamine antagonist with
      pressor properties.
AB  - We have synthesized and examined some of the pharmacological properties of 6-[N,S
      dimethyl-N'-cyanoisothioureidomethyl]-6,11-dihydro-5H- dibenz(b,e)azepine
      hydrochloride (Fran 12), a derivative of 6-methylaminomethyl-6,11-dihydro-5H-
      dibenz[b,e,]azepine. In the guinea-pig isolated ileum, Fran 12 (10(-7)-10(-5) M)
      caused parallel rightward shifts of the concentration-response curves to
      histamine. A Schild plot gave a pA2 of 7.48, with a slope not significantly
      different from -1.0. In the rat stomach fundus strip and in endothelium-denuded
      aortic rings, Fran 12 inhibited contractile responses to 5-hydroxytryptamine in a
      non-competitive manner. In both chloralose-anaesthetized and pithed rats, it
      inhibited pressor responses to 5-hydroxytryptamine. It had no effect on depressor
      responses to 5-hydroxytryptamine in anaesthetized rats. In pithed rats, Fran 12
      (0.25-2 mg/kg, i.v.) produced dose-dependent increases in blood pressure. These
      were not inhibited by i.v. phentolamine, prazosin, yohimbine, propranolol,
      methysergide, pentolinium or atropine but were inhibited by verapamil. These
      results indicate that Fran 12 is a histamine and 5-hydroxytryptamine antagonist
      which also exerts pressor effects via a peripheral action. The pressor action
      does not appear to be mediated via effects on alpha 1- or alpha 2-adrenoceptors,
      muscarinic or nicotinic cholinoceptors or 5-hydroxytryptamine receptors, although
      calcium channel activation may play a role.

PMID- 1360794
TI  - College of American Pathologists Conference XXII: Hemostasis and Atherosclerotic
      Disease. April 28-May 1, 1992.

PMID- 1360793
TI  - Electrocardiographic changes during acute treatment of hypertensive emergencies
      with sodium nitroprusside or fenoldopam.
AB  - BACKGROUND: Electrocardiograms are routinely obtained before and during the acute
      treatment of hypertensive emergencies, usually to rule out "ischemic changes."
      Despite a few anecdotal reports of electrocardiographic changes, little is known
      about the incidence and significance of such changes, or their relationship to
      the treatment used. METHODS: We prospectively analyzed 12-lead electrocardiograms
      from 21 patients admitted for hypertensive emergencies (average blood pressure,
      222 +/- 4/140 +/- 3 mm Hg). Patients were randomly assigned to treatment with
      sodium nitroprusside (n = 11) or the dopamine receptor agonist fenoldopam
      mesylate (n = 10). Electrocardiograms were obtained at baseline and within 30
      minutes of reaching goal blood pressure (diastolic blood pressure, 100 to 110 mm
      Hg). RESULTS: There was no significant effect of either drug treatment on PR
      interval, QRS duration, QT interval, or R-wave amplitude, and no major ST-segment
      changes were noted. During treatment with either drug, the average T-wave
      amplitude decreased in all leads except aVR. New T-wave inversions in lead V4
      occurred in two and four patients after fenoldopam and nitroprusside treatment,
      respectively. There were no clinically apparent episodes of myocardial ischemia
      in any patient. CONCLUSIONS: Even in the absence of obvious myocardial ischemia,
      a decrease in T-wave amplitude, including T-wave inversion, occurs commonly
      during acute blood pressure reduction in hypertensive emergencies, an observation
      that may be explained by the accompanying acute changes in cardiac chamber
      volumes.

PMID- 1360795
TI  - A specific RFLP type associated with the occurrence of sheep scrapie in Japan.
AB  - We have investigated restriction fragment length polymorphism (RFLP) on the PrP
      gene and the frequencies of RFLP patterns in 35 healthy Suffolk sheep randomly
      collected. According to the combinations of PrP encoding DNA fragments generated
      by restriction enzymes Eco RI and Hind III, the RFLP patterns were classified
      into six types and designated as types I to VI. The frequencies of these types
      were as follows: I, 8.6%; II, 11.4%; III, 17.6%; IV, 11.4%; V, 28.6%; and VI,
      22.9%. In 10 sheep diagnosed as having natural scrapie, RFLP types, I, III, IV,
      and V were determined. To examine the correlation between the RFLP type and the
      occurrence of scrapie, the frequencies of RFLP types in sheep infected with
      natural scrapie were compared with those in healthy sheep. It was found that the
      frequency of type I in the sheep with natural scrapie was 70%, about eight times
      higher than that in randomly collected healthy sheep. In the 13 experimentally
      infected sheep that had been used for other purposes, however, no relationship
      between the RFLP type and onset of scrapie was found.

PMID- 1360796
TI  - The Canadian Forces Airsickness Rehabilitation Program, 1981-1991.
AB  - Airsickness is a significant obstacle in the training of some student pilots.
      When conventional therapy fails, desensitization therapy may be indicated. Using
      experience gained by the RAF and USAF, the Canadian Forces (CF) began such a
      program in 1981. This paper reports program results from 1981-1991. Following
      subject identification, treatment consists of three phases: biofeedback
      relaxation therapy, ground-based desensitization training and in-flight
      desensitization therapy with a pilot-flight surgeon. Employing a definition of
      cure used by the RAF, success was compared with that of the RAF and USAF
      programs. A total of 22 student pilots have undergone rehabilitation, 17 of whom
      have been successfully treated for a success rate of 77%. This is comparable to
      success rates of other programs. It is reaffirmed that desensitization is a valid
      clinical tool in treatment of airsickness.

PMID- 1360797
TI  - The spontaneously hypertensive rat (SHR) as an animal model of childhood
      hyperactivity (ADHD): changed reactivity to reinforcers and to psychomotor
      stimulants.
AB  - Childhood hyperactivity (attention-deficit hyperactivity disorder, ADHD) is a
      behavior disorder affecting 2-6% of grade-school children. The main symptoms are
      attention problems and hyperkinesis. The disorder is commonly treated with
      psychomotor stimulants, usually methylphenidate hydrochloride (ritalin) or d
      amphetamine. Neither the cause of the disorder nor the basis of the effectiveness
      of the drug treatment is well understood. Differences in reinforcement processes
      have been implicated as part of the underlying problem. The main purpose of the
      present research was to investigate reinforcement processes and motor
      characteristics with and without stimulant medication in SHR, as an animal model
      of ADHD, and WKY controls, its normoactive progenitor strain. SHR behavior turned
      out to be more sensitive to immediate reinforcement and proportionately less
      sensitive to delayed reinforcement when compared to the behavior of WKY, as
      demonstrated by systematic changes in rates of responding throughout fixed
      interval schedules of reinforcement of bar-presses by water. The psychomotor
      stimulants weakened the control by immediate reinforcers and strengthened the
      control by delayed reinforcers, with the effect of the drugs being more
      pronounced in WKY than in SHR. The results are consistent with clinical
      observations that ADHD children are less willing than others to accept "delayed
      gratification" and that methylphenidate increases the control of delayed reward
      over their behavior.

PMID- 1360798
TI  - Effects of medetomidine, an alpha-2 adrenoceptor agonist, and atipamezole, an
      alpha-2 antagonist, on spatial memory performance in adult and aged rats.
AB  - The effects of a novel, highly selective alpha-2 agonist, medetomidine, and its
      antagonist, atipamezole, were studied on the working memory of rats performing a
      spatial delayed alternation task. Testing was performed in two stages, at the age
      of 8.3 months (mean) and again when the rats were 17.6 months (mean). A low dose
      (3 micrograms/kg) and a high dose (30 micrograms/kg) of medetomidine improved the
      performance of the old rats in the memory task but had no effect on the young
      rats. The dose-response curve of medetomidine resembles that of guanfacine,
      another alpha-2 agonist. At the low dose of medetomidine (3 micrograms/kg) the
      animals showed no signs of sedation. Since medetomidine even at a low dose has a
      beneficial effect on the memory performance of old rats, it could be a good
      candidate for the treatment of age-associated memory dysfunction.

PMID- 1360799
TI  - Protective effects of verapamil on cis-platinum and carboplatinum nephrotoxicity
      in dehydrated and normohydrated rats.
AB  - The aim of the study was to compare the nephrotoxic effects of cis-platinum
      (CDDP) and carboplatinum (CBDCA) and the protective potential of verapamil in
      rats. CDDP (3 mg/kg) and CBDCA (60 mg/kg) were administered intraperitoneally in
      a single dose on day 1. Verapamil (0.1 mg/kg) was administered 30 min before i.p.
      injection. Rats were assayed daily for urinary excretion of N-acetyl-beta-D
      glucosaminidase (NAG), alkaline phosphatase (AP) and gamma-glutamyl-transferase
      (GMT), on day 3 they were assayed for creatinine clearance. CBDCA appears to be
      less nephrotoxic than CDDP. Verapamil shows protective effects against the
      nephrotoxicity of platinum derivatives in both groups of rats.

PMID- 1360800
TI  - A chemiluminescence fiber-optic biosensor system for the determination of
      glutamine in mammalian cell cultures.
AB  - A chemiluminescence fiber-optic biosensor system has been developed for
      determining glutamine in hybridoma cell cultures producing monoclonal antibodies
      against viral surface antigens. Glutaminase and glutamate oxidase (GLO) were
      immobilized onto aminopropyl glass beads via glutaraldehyde activation separately
      and packed in a column. Two separate columns containing immobilized GLO and
      catalase were placed upstream to eliminate endogenous glutamate. In the presence
      of ferricyanide, luminol reacted with hydrogen peroxide released from the
      enzymatic reactions to produce a chemiluminescence (CL) light signal which was
      detected and quantitated with a fiber-optic system. In combination with flow
      injection analysis it was possible to process samples virtually identically, thus
      avoiding difficulties in reproducing the CL signal. There was an excellent linear
      relationship between the CL response and standard glutamine concentration in the
      range 10(-6) to 10(-3) M. A complete analysis could be performed in 2 min
      including sampling and washing. Each immobilized enzyme column was stable for at
      least 300 repeated analyses without any loss of activity. When the biosensor
      system was used for the determination of glutamine in spent mammalian cell
      cultures, the values obtained compared well with those of high-performance liquid
      chromatography, thus validating the applicability of the CL fiber-optic system.

PMID- 1360801
TI  - Further data on the development of SRIF-like immunoreactive nerve cell
      populations in the chick embryo brain stem. I. Medulla and pons.
AB  - Further immunocytochemical analysis of the neuroblasts with SRIF-like
      immunoreactivity (ir) was carried out on the chick embryo medulla and pons. 5 or
      100 microns rombencephalon sections were obtained from 60 White Leghorn chick
      embryos at stages (E = Embryonic days) ranging from E4 1/2 to E18 and incubated
      with rabbit polyclonal antibodies against synthetic cyclic Somatostatin-14,
      according to PAP-DAB technique. In the medulla and pons the ir appeared as from
      E12. From E12 to E13 1/2-E14 the ir distribution gradually changed. From E14 to
      E18 numbers and spatial arrangement of the positive neuroblast groups did not
      show substantial changes; in these respects the ir distributional pattern proved
      to be markedly different from the one observed by the Authors in adult animals.
      Moreover, from E13 to E15 the positive neuroblast density appeared to be higher
      than that of positive neurons in adults. These results are consistent with a
      possible SRIF local regulative role.

PMID- 1360802
TI  - Further data on the development of SRIF-like immunoreactive nerve cell
      populations in the chick embryo brain stem. II. Midbrain tegmentum.
AB  - Further immunocytochemical analysis of the neuroblasts with SRIF-like
      immunoreactivity (ir) was carried out on the chick embryo midbrain tegmentum. 5
      or 100 microns mesencephalon sections were obtained from 60 White Leghorn chick
      embryos at stages (E = Embryonic days) ranging from E4 1/2 to E18 and incubated
      with rabbit polyclonal antibodies against synthetic cyclic Somatostatin-14,
      according to PAP-DAB technique. In the midbrain tegmentum the ir appeared as from
      E12. From E12 to E13 1/2-E14 the ir distribution gradually changed. From E14 to
      E18 numbers and spatial arrangement of the positive neuroblast groups did not
      show substantial changes; in these respects the ir distributional pattern proved
      to be similar to the one observed by the Authors in adult animals. From E17 to
      E18 a decrease in the positive neuroblast density appeared to occur, particularly
      in a ventrally placed group. These results are consistent with a possible local
      regulative role of the SRIF.

PMID- 1360803
TI  - Comparison of the efficacy of esmolol and alfentanil to attenuate the hemodynamic
      responses to emergence and extubation.
AB  - STUDY OBJECTIVE: To define the ability of esmolol and alfentanil to control the
      hemodynamic changes associated with extubation and emergence. DESIGN: Randomized,
      double-blind, placebo-controlled study. SETTING: General surgery operating rooms
      at a university hospital. PATIENTS: Forty-two ASA physical status I and II
      patients without history of cardiac or pulmonary disease undergoing surgery not
      involving the cranium or thorax. INTERVENTIONS: Patients were given either a
      bolus dose of normal saline followed by an infusion of normal saline, a bolus
      dose of alfentanil 5 micrograms/kg followed by an infusion of normal saline, or a
      bolus dose of esmolol 500 micrograms/kg followed by an infusion of esmolol 300
      micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Emergency and extubation
      resulted in significant increases in heart rate (HR) and blood pressure (BP) in
      the placebo group. Alfentanil controlled the responses to emergence but prolonged
      the time to extubation (p < 0.05). Esmolol significantly controlled the responses
      to emergence and extubation (p < 0.05). CONCLUSIONS: Emergence and extubation
      after inhalation general anesthesia result in significant increases in BP and HR
      in healthy patients. An esmolol bolus dose and subsequent infusion significantly
      attenuated these responses. A small bolus dose of alfentanil minimized the
      responses to emergence but prolonged the time to extubation and was no longer
      protective at that point.

PMID- 1360804
TI  - Platelet-derived growth factor (PDGF) A-chain mRNA heterogeneity generated by the
      use of alternative promoters and alternative polyadenylation sites.
AB  - Expression of the platelet-derived growth factor (PDGF) A-chain gene is known to
      give rise to multiple transcripts of different sizes. Northern blot analysis,
      using a set of DNA probes corresponding to various parts of the human PDGF A
      chain gene, indicated heterogeneity in both the 5' and 3' end of the transcripts.
      The 3' heterogeneity was shown to be the result of differential use of three
      polyadenylation signals. S1-nuclease protection- and chloramphenicol
      acetyltransferase (CAT)-assays, revealed the 5' heterogeneity to be the
      consequence of two alternative promoters. Whereas the upstream promoter contained
      typical TATA- and CAAT-boxes, the downstream promoter lacked a TATA-box but
      seemed to be composed of several GC-boxes.

PMID- 1360805
TI  - Resistance of HIV-1 to AZT might also involve the cellular expression of
      multidrug resistance P-glycoprotein.
AB  - Resistance of tumor cells to the antigrowth activity of several cytotoxic
      compounds has been associated with the expression of the so-called multidrug
      resistance protein or P-glycoprotein. This article addresses the question whether
      the expression of such protein could also affect the sensitivity of HIV to AZT.
      Our data indicate that this possibility does exist. In fact, multidrug-resistant
      CEM VBL100 cells, which express high levels of P-glycoprotein, are less sensitive
      to both the antiproliferative activity and the antiviral action of AZT.
      Additionally, our data suggest that this phenomenon is specifically mediated by P
      glycoprotein since trifluoroperazine, which is known to circumvent multidrug
      resistance due to the action on P-glycoprotein, increases the intracellular
      accumulation of AZT and affects the sensitivity of HIV to AZT. Although the
      biological and clinical significance of these observations has still to be
      established, this study suggests that cellular factors, other than virus itself,
      should be taken into account to address the phenomenon of drug resistance of HIV.

PMID- 1360806
TI  - Complex correlations between the morphology, electrophysiology and peptide
      immunohistochemistry of guinea-pig enteric neurones.
AB  - Neuroanatomical, electrophysiological and immunohistochemical techniques were
      used to describe correlations between soma morphology and electrophysiological
      properties in two groups of guinea-pig enteric neurones posing particular
      challenges. Lucifer Yellow-staining of 542 myenteric plexus neurones of duodenum
      revealed a great diversity of neuronal morphology. The distribution was: Dogiel
      Type I 27%, Dogiel Type II 54%, Stach Type IV 9%; 10% were unclassified.
      Correlations were sought in 59 of these cells between morphology and
      electrophysiological properties but no particular association was recognised.
      Dynorphin A(1-8)-like immunoreactivity (Dyn A(1-8)-IR) was found in up to 90% of
      identified submucous neurones of guinea-pig ileum. Of 62 S-neurones, 41 showed
      'weak' and 19 had 'intense' Dyn A (1-8)-IR. There was no evidence of Dyn A(1-8)
      IR in 2 S-neurones, nor in 8/8 AH-neurones. As for 11/16 vasoactive intestinal
      peptide- (VIP-) IR neurones, there was a strong correlation between the presence
      of 'weak' Dyn A(1-8)-IR and the occurrence of inhibitory (IPSPs) and slow
      excitatory synaptic potentials (EPSPs) (13/16 cells tested), which were never
      observed in neurones with 'intense' Dyn A(1-8)-IR (16/16) or neuropeptide Y (NPY)
      IR (8/8). Similarly, 7/7 neurones with 'weak' Dyn A(1-8)-IR, but not those (7/7)
      with 'intense' Dyn A(1-8)-IR, hyperpolarised or showed a conductance change to
      noradrenaline. It was concluded that dynorphin A(1-8)-like-IR was contained in
      two populations of submucous neurone that are anatomically,
      immunohistochemically, electrophysiologically and pharmacologically distinct and
      closely related to those containing VIP and NPY. Furthermore, as in the myenteric
      plexus throughout the small intestine, opioid peptides are not expressed in
      Dogiel Type II cells.

PMID- 1360807
TI  - Assessment of the anticholinergic effect of the new antihistamine mizolastine in
      healthy subjects.
AB  - 1. Twelve healthy subjects were enrolled in a double-blind placebo controlled
      cross-over study in order to assess the possible anticholinergic effects of four
      doses of a new antihistamine compound, mizolastine, compared with hyoscine
      butylbromide (HBB) used as a reference anticholinergic drug. 2. Although
      mizolastine, a potent and selective H1-receptor blocker has no affinity for
      muscarinic receptors and does not antagonize the effects of carbachol in rodents,
      a study was initiated to investigate its effects on various effectors possessing
      muscarinic receptors (eye, heart, sweat gland, salivary gland). 3. HBB (40 mg,
      s.c.) impaired accommodation, decreased salivary flow and inhibited cardiac sinus
      arrhythmia. Pupil diameter and maximum constriction speed, carbachol-induced skin
      sweating and Valsalva ratio were unaffected. 4. Mizolastine (5, 10, 20, 40 mg
      p.o.) did not affect any parameter at any time point, demonstrating a lack of
      anticholinergic effect.

PMID- 1360808
TI  - Polyarteritis nodosa presenting with hypertensive encephalopathy.
AB  - Polyarteritis nodosa (PAN) is a rare cause of malignant hypertension. As far as
      we are aware, hypertensive encephalopathy has not been described in the
      literature as a presenting feature of PAN.

PMID- 1360809
TI  - Chromosomal localisation of two putative 11p oncosuppressor genes involved in
      human ovarian tumours.
AB  - In this study, 44 primary or metastatic human ovarian tumours were tested for
      allelic deletions on the short arm of chromosome 11. Analysis of 12 polymorphic
      loci by Southern blotting evidenced loss of heterozygosity (LOH) in at least one
      locus in 41% of cases. Moreover, two hot spots of deletions were tentatively
      mapped on 11p13 and 11p15.5. Our results demonstrated that LOH at 11p is a common
      event in ovarian carcinomas and were indicative of the possible existence in 11p
      of two oncosuppressor genes involved in ovarian carcinogenesis. The similarity
      observed with 11p allelic losses in Wilms tumours, clustered in 11p13 and 11p15.5
      too, suggests that deletion and possibly inactivation of the same growth
      regulatory genes (WT genes) could also contribute to development of the malignant
      phenotype in ovarian carcinomas. Finally, a statistically significant association
      (P = 0.005) between 11p deletions and hepatic involvement was suggested by the
      analysis of distribution of 11p LOH relative to different clinical and
      pathological parameters of the tumour patients.

PMID- 1360810
TI  - Identification of a retinoic acid responsive enhancer 3' of the murine homeobox
      gene Hox-1.6.
AB  - The putative vertebrate morphogen retinoic acid (RA) has been shown to induce
      expression of many mammalian homeobox genes in cell lines, suggesting expression
      of this gene family in developing vertebrate embryos may be controlled in part by
      RA. Using the teratocarcinoma cell line F9 as a model system, we have studied the
      RA-response of the murine homeobox gene Hox-1.6. RA treatment of F9 cells causes
      the appearance of a DNAse I hypersensitive site 3' of Hox-1.6, approximately 5 kb
      downstream of the Hox-1.6 promoter, and this site has been shown to reflect the
      presence of an RA-responsive enhancer 3' of the gene. The RA-responsiveness of
      the enhancer is controlled by a retinoic acid responsive element (RARE) identical
      to the RARE of the retinoic acid receptor (RAR) beta gene; however, other
      sequences also influence the activity of the enhancer, suggesting the presence of
      binding sites for novel proteins which regulate Hox-1.6 expression. Experiments
      with Hox-1.6 minigenes in which lacZ expression is controlled by the Hox-1.6
      promoter and enhancer demonstrate that it is the 3' enhancer which confers RA
      responsiveness on the endogenous promoter, as constructs which lack the enhancer,
      or the RARE alone, do not respond to RA. Our results support the idea that RA is
      an endogenous vertebrate morphogen; identification of the RA-responsive enhancer
      downstream of Hox-1.6 demonstrates that RA directly controls the transcription of
      at least one member of a gene family that determines tissue identity in the
      vertebrate embryo.

PMID- 1360811
TI  - Studies on concentrations of NA and HVA and activity of DBH in the serum from
      schizophrenic patients, first-degree relatives and normal subjects.
AB  - The serum noradrenaline (NA), homovanillic acid (HVA) and dopamine beta
      hydroxylase (DBH) have been examined in neuroleptic-free and -treated patients,
      healthy first-degree relatives of the patients and normal subjects. Analysis of
      variance (ANOVA) revealed significant differences in the concentrations of serum
      NA(F = 2.91, p < 0.05) and HVA (F = 3.58, p < 0.05), and in the activity of serum
      DBH (F = 2.77, p < 0.05) among the four groups. The serum NA was significantly
      higher in neuroleptic-free patients (475 +/- 220 pg/ml, n = 18), than in healthy
      first-degree relatives (343 +/- 189 pg/ml, n = 37, p < 0.05) or in normal
      subjects (354 +/- 111 pg/ml, n = 17, p < 0.05), and it also was significantly
      higher in neuroleptic-treated patients (442 +/- 223 pg/ml, n = 58) than in
      healthy first-degree relatives (p < 0.05) or in normal subjects (p < 0.05). There
      was a trend towards high serum HVA in neuroleptic-free patients (11.3 +/- 6.3
      ng/ml, n = 17) compared with the other three groups. The serum DBH activity was
      high in neuroleptic-free patients (31.2 +/- 15.6 nmol/min/ml, n = 17), and
      significantly in comparison with those treated with neuroleptic drugs (21.6 +/-
      10.9 nmol/min/ml, n = 56, p < 0.05). There was a significant negative correlation
      between HVA concentration and DBH activity in the serum from neuroleptic-free
      patients (r = -0.64, n = 16, p < 0.01), and there appeared to be three subgroups
      with alterations of serum DBH activity and HVA concentration.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1360812
TI  - Smoking and schizophrenia.
AB  - Several studies have shown that patients with schizophrenia have an extremely
      high prevalence of smoking, almost 90%, compared to only 33% in the general
      population and 45-70% in patients with other psychiatric diagnoses. The reasons
      for the high prevalence of smoking among schizophrenics is unknown, but it is
      likely that smoking behavior in schizophrenia may be a complex process, related
      to numerous interrelationships between the psychopathological, biochemical, and
      neuropharmacological aspects of smoking and of schizophrenia.

PMID- 1360813
TI  - Thermodynamic effects of active-site ligands on the reversible, partial unfolding
      of dodecameric glutamine synthetase from Escherichia coli: calorimetric studies.
AB  - Dodecameric glutamine synthetase (GS) from Escherichia coli undergoes reversible,
      thermally induced partial unfolding without subunit dissociation. A single
      endotherm for Mn.GS (+/- active-site ligands) in the presence of 1 mM free Mn2+
      and 100 mM KCl at pH 7 is observed by differential scanning calorimetry (DSC).
      Previous deconvolutions of DSC data for Mn.GS showed only two two-state
      transitions (with similar tm values; 51.6 +/- 2 degrees C), and indicated that
      cooperative interactions link partial unfolding reactions of all subunits within
      the Mn.enzyme dodecamer [Ginsburg, A., & Zolkiewski, M. (1991) Biochemistry 30,
      9421]. A net uptake of 8.0 equiv of H+ by Mn.GS occurs during partial unfolding,
      as determined in the present DSC experiments conducted with four buffers having
      different heats of protonation at 50 degrees C. These data gave a value of 176 +/
      12 kcal (mol of dodecamer)-1 for delta Hcal corrected for buffer protonation. L
      Glutamine and L-Met-(SR)-sulfoximine stabilize the Mn.GS dodecamer through the
      free energies of ligand binding, and these were shown to be partially and totally
      released, respectively, from the 12 active sites at high temperature. Ligand
      effects on Tm values from DSC were similar to those from spectral measurements of
      Trp and Tyr exposures in two subunit domains. Effects of varying [ADP] on DSC
      profiles of Mn.GS were complex; Tm is increased by low [ADP] and decreased by >
      100 microM free ADP. This is due to the exposure of an additional low-affinity
      ADP binding site per GS subunit at high temperature with log K1' = 4.3 and log
      K2' = 3.6 at 60 degrees C relative to log K' = 5.5 for ADP binding at 30 degrees
      C, as determined by isothermal calorimetric and fluorescence titrations.
      Moreover, delta Hcal at > 27% saturation with ADP (corrected for ADP
      binding/dissociation) is approximately 80-100 kcal/mol more than in the absence
      of ligands. Changes in domain interactions could result from ADP bridging subunit
      contacts in the dodecamer. Each of the active-site ligands investigated here
      produces different effects on DSC profiles without uncoupling the extremely
      cooperative, partial unfolding reactions in the Mn.GS dodecamer.

PMID- 1360814
TI  - Cytokine expression and endothelial cell and lymphocyte activation in human
      cardiac allograft rejection: an immunohistochemical study of endomyocardial
      biopsy samples.
AB  - We used monoclonal antibodies and immunohistochemical staining of frozen tissue
      sections to study the expression of cytokines in human cardiac allograft
      rejection. The 113 endomyocardial biopsy samples were stained for interleukin
      (IL)-2, IL-6, and interferon-gamma. The findings were compared to expression of
      the endothelial cell adhesion molecule ICAM-1, and the lymphocyte receptor for
      the adhesion molecule VCAM-1, VLA-4. Four biopsy samples from patients with
      idiopathic cardiomyopathy served as controls. IL-2 was not expressed in
      lymphocytes of controls and only occasionally in mild or moderate cellular
      rejection, humoral rejection, and Quilty lesions. IL-2 expression was prominent
      in severe cellular rejection. Interferon-gamma expression increased in proportion
      to the severity of cellular rejection and was not expressed in other conditions.
      IL-6 staining, which was only observed in occasional cases, was mild. Cytokine
      and adhesion molecule expression tended to increase with the severity of cellular
      rejection. This study shows that cytokine expression can be documented in human
      allograft endomyocardial biopsy samples with immunohistochemical techniques. The
      findings support the concept of an important role for cytokines in human cardiac
      allograft rejection.

PMID- 1360815
TI  - An overview of membrane, cytosolic and nuclear proteins associated with the
      expression of resistance to multiple drugs in vitro.

PMID- 1360816
TI  - Hematopoietic stem cell gene replacement therapy.

PMID- 1360817
TI  - The sensitive determination of abanoquil in blood by high-performance liquid
      chromatography/atmospheric pressure ionization mass spectrometry.
AB  - A method is described for the determination of abanoquil in human blood. The
      method is based on high-performance liquid chromatography (HPLC)/atmospheric
      pressure positive ion chemical ionization mass spectrometry, using (2H3)abanoquil
      as internal standard. Multiple reaction monitoring is employed for selectivity
      and sensitivity, which enables quantification over the range 10-500 pg ml-1 with
      acceptable precision and accuracy. This assay methodology illustrates the
      versatility of atmospheric pressure ionization/tandem mass spectrometry, in
      conjunction with HPLC, for the separation and quantification of drugs in the
      subnanogram per millilitre range.

PMID- 1360818
TI  - Thermospray tandem mass spectrometric (TS MS-MS) investigation of the main
      metabolite of umespirone (KC-9172)

PMID- 1360819
TI  - Laboratory and phase I studies of new cancer drugs.
AB  - New drug discovery continues to follow the time-honored paths of screening and
      novel target identification combined with analogue development and serendipity.
      The agents selected here reflect these various approaches. They include drugs
      already showing significant antitumor activity, eg, anthrapyrazoles,
      temozolomide, camptothecin analogues, and taxotere, and updated information is
      provided on their development. Other drugs just entering or currently in phase I
      trials include rhizoxin, which seems capable of overcoming multidrug resistance;
      the novel bioreductive agent EO9 [corrected]; and bryostatin, a highly potent
      protein kinase C agonist. Sequence specificity could well prove to be an
      important factor in the development of DNA-interactive agents, and information is
      provided on the progress with distamycin mustard and the new
      cyclopropylpyrroloindole analogues carzelesin and adozelesin.

PMID- 1360820
TI  - Cytotoxicity of adriamycin, idarubicin, and vincristine in acute myeloid
      leukemia: chemosensitization by verapamil in relation to P-glycoprotein
      expression.
AB  - A 4-day colorimetric tetrazolium dye (MTT) assay was used to assess the
      cytotoxicity of adriamycin (ADM), vincristine (VCR), and idarubicin (IDA) in
      blasts isolated from 37 patients with newly diagnosed and pretreated acute
      myeloid leukemia (AML). The effect of verapamil (VRP) as a chemosensitizer was
      studied in relation to the expression of the membrane efflux pump P-glycoprotein
      (PGP) as determined by a semiquantitative flow-cytometric proceder. A slight
      positive correlation was found between the fraction of cells expressing PGP and
      the ID50 values for ADM and VCR, but not between cellular PGP content and
      sensitivity to IDA. The overall data showed no significant sensitization effect
      of VRP. However, in specimens with more than 10% cells expressing PGP, 2 microM
      VRP sensitized cells to ADM and VCR significantly. The median of sensitization
      ratios (SRs), i.e., the ratios of cytotoxic drug ID50 in the absence/presence of
      VRP, were 1.89 and 2.0, respectively. No sensitizing effect of VRP on the
      cytotoxicity of IDA was observed. Related to the clinical status, the median
      fraction of PGP-positive blasts was elevated fourfold in pretreated patients (n =
      16) in comparison to patients with de novo AML (n = 19). No differences in ID50
      values were observed between newly diagnosed and pretreated patients. However,
      SRs for ADM and VCR were higher in samples of pretreated patients compared with
      de novo AML. PGP-mediated cellular drug resistance may thus be circumvented in
      leukemic blasts by application of chemosensitizers or, potentially, alternative
      anthracyclines.

PMID- 1360821
TI  - PCR-determined expression of the MDR1 gene in chronic lymphocytic leukemia.
AB  - To determine the role the multiple drug-resistance (MDR 1) gene plays in chronic
      lymphocytic leukemia (CLL), we measured the expression of the MDR 1 gene in 30
      patients with this disease. A rapid, highly sensitive, and nonradioactive
      technique based on the polymerase chain reaction (PCR) was used for that purpose.
      In this technique, called differential PCR, the target (MDR 1) and a reference
      gene (beta 2-microglobulin) are co-amplified by PCR from random hexamer-primed
      cDNA in the same reaction vessel. The level of target gene expression is
      reflected in the ratio between the intensities of the two resulting PCR product
      bands, as measured by high-performance liquid chromatography (HPLC). MDR 1 gene
      expression was detectable in 29/30 (97%) patients with CLL, with a median
      expression level of 0.36 U (human placenta = 1 U). There was no correlation
      between expression of the MDR 1 gene and clinical stage, time from diagnosis,
      absolute lymphocyte count, several lymphocyte surface markers, or prior treatment
      in the patients analyzed. Immunocytochemical studies of the same material using
      the monoclonal antibody C219 showed a very low or undetectable expression of the
      P-glycoprotein in the lymphocytes of all patients studied, whereas granulocytes
      were significantly more immunoreactive. We conclude that the level of expression
      of the MDR 1 gene in CLL is generally low, that the removal of granulocytes is
      important in studies of expression of MDR 1 mRNA in CLL, and that differential
      PCR provides a rapid and reliable method for quantifying the amount of a specific
      mRNA, even in very small samples of total RNA.

PMID- 1360822
TI  - Effect of tissue perfusion and oxygenation on accumulation of collagen in healing
      wounds. Randomized study in patients after major abdominal operations.
AB  - OBJECTIVE: To compare the accumulation of collagen in standardised wounds in
      patients who had abdominal operations and whose postoperative fluid replacement
      was decided either clinically or by measurements of subcutaneous oxygen tension
      (PscO2). DESIGN: Prospective randomised trial. SETTING: University Hospital.
      SUBJECTS: Twenty-nine patients with cancer or inflammatory bowel disease who were
      undergoing abdominal operations. INTERVENTIONS: Silicone rubber catheter placed
      in the upper arm to measure PscO2. Two tubes of expanded polytetrafluoroethylene
      (ePTFE) implanted subcutaneously parallel to the silicone rubber catheter to
      measure the amount of collagen accumulated. MAIN OUTCOME MEASURES: Amount of
      postoperative fluid replacement required in each group, and measurements of
      hydroxyproline/cm of the ePTFE tubes. RESULTS: The group treated according to
      PscO2 measurements received more fluid on the day of operation than the group
      treated according to clinical criteria (p < 0.05). They had accumulated more
      collagen in their ePTFE tubes by day 7 (p < 0.05). CONCLUSION: Replacement of
      fluid according to measurements of PscO2 rather than by clinical criteria results
      in improved accumulation of collagen in healing wounds.

PMID- 1360823
TI  - Ultrasonographic screening for abdominal aortic aneurysm.
AB  - OBJECTIVE: To assess the prevalence of abdominal aortic aneurysm in a selected
      group of men over the age of 60, and define main risk factors. DESIGN: Population
      based screening study. SETTING: Private Norwegian health maintenance
      organisation. SUBJECTS: 500 men over the age of 60 years. INTERVENTIONS: General
      examination by a general practitioner, together with measurements of blood
      glucose and serum cholesterol concentrations. Abdominal scan with a B-mode
      ultrasound imager. MAIN OUTCOME MEASURES: An increase in the diameter of the
      aorta of more than 150% over the diameter at the origin of the superior
      mesenteric artery, or maximum diameter of more than 29 mm. Correlation with
      history of smoking, serum cholesterol concentration, and general health. RESULTS:
      29 patients (5.8%) had small, and 12 (2.4%) had large, abdominal aortic
      aneurysms. There was a significant association between aortic aneurysm and
      history of smoking (p < 0.01), poor health (defined as coexistent hypertension,
      cardiovascular disease, or diabetes mellitus) (p < 0.01), and increasing age (p =
      0.025). There was no association with hypercholesterolaemia. CONCLUSION:
      Ultrasonic screening of groups at risk followed by elective operation may reduce
      mortality of abdominal aortic aneurysm.

PMID- 1360824
TI  - Association between perioperative blood transfusion and postoperative infection
      in patients having elective operations for gastrointestinal cancer.
AB  - OBJECTIVE: To assess the effect of blood transfusion on the development of
      infection after elective operations for gastrointestinal and pancreatic cancer.
      DESIGN: Prospective open study. SUBJECTS: 285 consecutive patients admitted with
      gastric, colorectal, and pancreatic cancer, 215 of whom were suitable for the
      study. MAIN OUTCOME MEASURES: Sex, age, total iron binding capacity, measurement
      of haemoglobin and serum albumin concentration, assessment of immune response by
      delayed hypersensitivity skin test, and weight loss were recorded, as were
      duration of operation, operative blood loss, and pathological TNM stage of the
      disease. RESULTS: Sixty patients (28%) developed infections postoperatively.
      Univariate analysis showed that the development of infection was significantly
      associated with the amount of blood transfused (p < 0.001), operative blood loss
      (p < 0.05), and length of operation (p < 0.01), but not weight loss (p = 0.07) or
      delayed hypersensitivity response (p = 0.08). Multiple logistic analysis showed
      that blood transfusion was a significant independent variable only when more than
      1,000 ml were transfused (odds ratio 6.5, p < 0.05). CONCLUSION: Transfusion of
      more than 1,000 ml of blood is an independent risk factor in the development of
      infection postoperatively in patients undergoing operations for gastrointestinal
      cancer.

PMID- 1360825
TI  - Value of computed tomography in preoperative evaluation of resectability and
      staging in oesophageal carcinoma.
AB  - OBJECTIVE: To evaluate computed tomography (CT) as a method of staging patients
      with oesophageal carcinoma. DESIGN: Retrospective study. SETTING: Ullevaal
      Hospital, Oslo, Norway. SUBJECTS: 85 patients who presented with oesophageal
      carcinoma between February 1982 and December 1989. INTERVENTIONS: Assessment by
      CT was made in all patients. MAIN OUTCOME MEASURES: Correlation with findings at
      operation, and histological examination of operative specimens. RESULTS: From the
      findings at operation in the 46 patients who were operated on (resection, n = 39;
      exploration only, n = 7) the sensitivity, specificity, and accuracy of CT staging
      of the growth were 80%, 91%, and 88%, and when histological confirmation of
      infiltration was taken into consideration the figures were 25%, 84%, and 54%,
      respectively. The sensitivity, specificity, and accuracy of CT detection of lymph
      node metastases were 22%, 95%, and 55%. CONCLUSION: Staging of oesophageal cancer
      with CT before operation is useful in judging resectability, but the smaller
      tumours should be assessed with caution. CT is unreliable in the diagnosis of the
      depth of infiltration and the presence of lymph node metastases compared with
      histological examination.

PMID- 1360826
TI  - Serum interleukin-6 and C reactive protein responses in patients after
      laparoscopic or conventional cholecystectomy.
AB  - OBJECTIVE: To investigate the acute phase inflammatory response to surgical
      trauma after laparoscopic and conventional cholecystectomy. DESIGN: Prospective
      open study. SETTING: University Hospital in The Netherlands. SUBJECTS: 21
      patients with symptomatic cholelithiasis admitted for elective cholecystectomy
      who had had no previous upper abdominal operations. INTERVENTIONS: 12 patients
      underwent conventional, and 9 patients laparoscopic, cholecystectomy. Circulating
      interleukin-6 (IL-6) and C reactive protein concentrations were measured 6, 12,
      24 and 48 hours after operation. MAIN OUTCOME MEASURE: Changes in IL-6 and C
      reactive protein concentrations, and comparison of operative blood loss and
      length of stay in hospital. RESULTS: Those treated by laparoscopic
      cholecystectomy lost significantly less blood (median 60 compared to 100 ml) and
      spent significantly fewer days in hospital (median 2 compared with 7 days), (p <
      0.01 in each case). The only changes in circulating IL-6 concentrations were seen
      in patients over the age of 60 years who underwent conventional cholecystectomy.
      There were significant differences in C reactive protein concentrations between
      the two operations at both 24 and 48 hours after the operation (p < 0.01 in each
      case). CONCLUSION: We conclude that laparoscopic cholecystectomy reduces the
      acute phase inflammatory response compared with the conventional operation; there
      seems to be no relevant correlation between plasma concentrations of IL-6 and C
      reactive protein; the presence of IL-6 does not affect the response of C reactive
      protein to trauma; and the response of IL-6 to trauma is age dependent.

PMID- 1360827
TI  - Early carcinoma of the gallbladder.
AB  - OBJECTIVE: To clarify the definition and clinicopathological characteristics of
      early cancer of the gallbladder. DESIGN: Open study. SETTING: University
      hospital. SUBJECTS: 78 patients with pathological stage T1a and 11 with pT1b
      tumours. INTERVENTIONS: Of those with pT1a tumours, 51 were treated by simple,
      and 27 by radical, cholecystectomy. For those with pT1b tumours the figures were
      5 and 11, respectively. RESULTS: There were two recurrences, both in patients
      with pT1a tumours, histological examination of which had shown tumour present at
      the surgical margins. There were no cases of neurovascular invasion but only one
      case of lymphatic invasion that was mild and restricted to the lamina propria in
      a patient with a pT1b tumour. The outcome in the rest was excellent. CONCLUSION:
      Most pT1 cancers spread locally. Complete resection results in cure regardless of
      the scope of the operation done. The main determinant of prognosis is the
      presence of tumour at the resection margins. All pT1 cancers can therefore be
      regarded as early cancers of the gallbladder.

PMID- 1360828
TI  - Routine early endoscopic cholangiography, sphincterotomy and removal of common
      duct stones in acute gallstone pancreatitis.
AB  - OBJECTIVE: To study the efficacy, safety and timing of endoscopic retrograde
      cholangiography (ERC) and sphincterotomy in patients with acute gallstone
      pancreatitis. DESIGN: Open study in Tampere University Hospital, Finland.
      SUBJECTS: 45 consecutive patients with acute gallstone pancreatitis who underwent
      ERC, with or without sphincterotomy. MAIN OUTCOME MEASURES: The results of early,
      compared with late, ERC with or without sphincterotomy. RESULTS: ERC was
      successful in all 45 patients. Ampullary impacted stone was found in eight.
      Common duct stones were found in 21 (47%) and sphincterotomy was successful in 19
      of these (90%). Nine patients developed complications (20%), five of the nine in
      whom severe disease had been predicted (56%) and four of the 36 in whom mild
      disease had been predicted (11%, p < 0.01). Three patients required operations
      for necrotising pancreatitis, in two of whom sphincterotomy had failed. There was
      no difference in outcome between the 21 patients who had ERC with or without
      sphincterotomy within 72 hours (median 48 h) of the onset of symptoms and the 24
      in whom it was delayed for a median of 144 hours. CONCLUSION: ERC and
      sphincterotomy may be done safely as a routine in patients with acute gallstone
      pancreatitis, and delay for a median of six days (range 3-14) from the onset of
      symptoms did not seem to affect the outcome in our patients.

PMID- 1360829
TI  - Delorme's operation for rectal prolapse in elderly or unfit patients.
AB  - OBJECTIVE: To evaluate the results after Delorme's operation for rectal prolapse
      in elderly and unfit patients. DESIGN: Retrospective analysis and telephone
      interview. SETTING: Akademiska sjukhuset, Uppsala, Sweden. SUBJECTS: A
      consecutive series of 14 women (median age 82, range 32-92) operated on for
      rectal prolapse 1987-1992 and followed up after a median of 18 months. RESULTS:
      There were no serious postoperative complications. Continence was improved in
      6/11 incontinent patients. The recurrence rate was 3/14 (21%). CONCLUSION:
      Delorme's operation is an attractive alternative in elderly or unfit patients,
      but is not recommended for younger and low risk patients because of the
      recurrence rate.

PMID- 1360830
TI  - The repair of difficult recurrent inguinal hernia using fascia lata graft.

PMID- 1360831
TI  - Multiple congenital internal hernias as a cause of acute abdominal symptoms in
      late adult life.

PMID- 1360832
TI  - Rare cause of late failure of polytetrafluoroethylene graft.

PMID- 1360833
TI  - Aneurysm of the thyrocervical trunk.

PMID- 1360834
TI  - Magnetic resonance imaging in preoperative assessment of choledochal cysts.

PMID- 1360835
TI  - Recurrent primary hydatid disease of the left quadriceps: the use of
      intraoperative ultrasonography.

PMID- 1360836
TI  - Colonic perforation: a rare complication in a patient with Ehlers-Danlos syndrome
      and von Willebrand's disease.

PMID- 1360837
TI  - Delayed diagnosis of extrahepatic biliary injury.

PMID- 1360838
TI  - Infection due to Staphylococcus warneri.

PMID- 1360839
TI  - Current concepts in embryonic craniofacial development.
AB  - Embryology mirrors phylogeny. The phenotypic expression of the genome is the
      result of differential gene transcription, the critically timed turning on and
      off of specific genes by transcription factors to produce cyto-, histo-, and
      morpho-differentiation that fleetingly reflects evolutionary stages of
      development during ontogeny. Hox genes regulate transcription of other structural
      genes and are responsible for patterning of the facial primordia. Cephalic
      development involves extremely complex morphogenetic mechanisms built on
      conserved elements that have undergone enormous evolutionary changes. Transient
      expression of phylogenetic origins characterize ontogeny and are reflected in
      defective development that may be due to inappropriate expression of Hox genes or
      distorted or disrupted epignetic processes. The mechanisms by which genetic
      information is transformed into morphological patterning by the actions of growth
      factors, morphogenes, and receptors are currently being identified. Biochemical,
      immunological, and allometric analyses of embryos and fetuses in experimental and
      descriptive studies are elucidating details of units of craniofacial
      morphogenesis--faciogenesis, palatogenesis, gnathogenesis, odontogenesis. Three
      dimensional model computer-assisted reconstruction of sectioned embryos and
      fetuses provides a further technique for understanding the complex configurations
      of tissue migratory patterns and growth sites that account for normal and
      abnormal craniofaciogenesis.

PMID- 1360840
TI  - X International Symposium on Hemoperfusion, Adsorbents and Immobilized
      Bioreactants. Rome, Italy.

PMID- 1360841
TI  - A model of the adrenergic beta-2 receptor and binding sites for agonist and
      antagonist.
AB  - From the known experimental data on adrenergic ligands and beta-2 receptor a
      model for the ligand binding sites was proposed and built. Agonist and antagonist
      have overlapping but different binding sites. The model correlates well with the
      structural information known from a series of adrenergic ligands.

PMID- 1360842
TI  - Synthesis and cardioselective beta-adrenergic antagonist activity of
      quinolyloxypropanolamines.
AB  - The synthesis and beta-adrenergic antagonist activities of (2R,2S)-, (2S)-, (2R)
      1-(5-quinolyloxy)-3-alkylamino-2-propanols (10-21) and (2R,2S)-1-(5
      isoquinolyloxy)-3-alkylamino-2-propanols (24-27) is described. beta 1-Adrenolytic
      (atria) structure-activity correlations indicated the N-alkyl substituent was a
      determinant of activity where the relative potency order was i-Pr and t-Bu >
      cyclohexyl. Compounds having the (2S)-configuration were more potent than the
      corresponding (2R)-analogs. The position of the heteroaryl nitrogen atom
      influences potency since the quinolyl analogs were ten-fold more active than the
      corresponding isoquinolyl isomers. All compounds in both the quinolyl and
      isoquinolyl series exhibited weak beta 2-adrenolytic activity (trachea), and high
      beta 1/beta 2 selectivity ratios when the N-alkyl substituent was i-Pr or t-Bu.
      The quinolyl ring system is an excellent bioisostere for the aryl moiety in
      aryloxypropanolamines since (2R,2S)- or (2S)-1-(5-quinolyloxy)-3-isopropyl (or t
      Bu) amino-2-propanols exhibit very potent and highly cardioselective beta 1
      adrenergic antagonist activities.

PMID- 1360843
TI  - Immunohistochemical determination of P-glycoprotein in a rat mammary tumour
      treated with tamoxifen.
AB  - The effect of treatment with the antiestrogen Tamoxifen on the distribution and
      localization of P-glycoprotein was determined by immunohistochemistry in a rat
      mammary tumour model, the R3230AC. Both in the untreated and the treated tumours,
      P-glycoprotein is unevenly expressed with numerous negative tumour cells and
      located predominantly in the cytoplasmic membranes. Administration of Tamoxifen
      significantly lowers P-glycoprotein content of the tumour studied.

PMID- 1360844
TI  - Abstracts of the 32nd Midwest Regional Developmental Biology Conference. Dayton,
      Ohio, May 13-16, 1992.

PMID- 1360845
TI  - 3rd International Symposium on Hypertension Associated with Diabetes Mellitus.
      Satellite of the American Society of Nephrology. Boston, Massachusetts, November
      21-23, 1992.

PMID- 1360846
TI  - Antihypertensive therapy in experimental diabetes.
AB  - Systemic hypertension is an important risk factor for the progression of diabetic
      glomerular disease. Recognition of this detrimental aspect has prompted intensive
      investigation into the mechanisms by which systemic hypertension promotes
      diabetic glomerulopathy, as well as into potential benefits of antihypertensive
      therapy. Studies in diabetic rats, both normotensive and hypertensive, have
      established that certain antihypertensive regimens effectively slow the
      development of albuminuria and glomerular sclerosis. Most consistently effective
      have been angiotensin-converting enzyme inhibitors, which may act to protect the
      kidney by several different mechanisms. Other antihypertensive regimens have been
      less consistent.

PMID- 1360847
TI  - HIV nursing: caring for the future. Summary proceedings, Amsterdam, July 19,
      1992.

PMID- 1360848
TI  - Influence of preoperative dexamethasone therapy on proliferating cell nuclear
      antigen (PCNA) expression in comparison to other parameters in meningiomas.
AB  - We conducted a trial in 42 benign and malignant meningiomas to assess a possible
      influence of preoperative dexamethasone therapy on mitotic index, labelling
      indices of proliferating cell nuclear antigen (PCNA), progesterone receptor,
      epidermal growth factor receptor (EGF-R), c-erbB-2 oncoprotein, cathepsin D,
      gamma-gamma enolase as well as the mean number of silver-stained nucleolar
      organizer region-associated proteins (AgNORs). Tumors with preceding
      dexamethasone therapy for more than 1 day display significantly less
      immunohistochemical staining for PCNA. A correlation between the labelling index
      of PCNA and the degree of malignancy could not be identified. There was no
      significant effect of preoperative dexamethasone therapy on the other parameters.
      Our data suggest that dexamethasone may selectively inhibit the expression of
      PCNA in the G1/S-phase of the cell cycle. Thus, we emphasize the necessity to
      heed factors, e.g. dexamethasone, which may affect the expression of
      proliferating markers.

PMID- 1360849
TI  - Morphometric changes in GH-immunoreactive adenohypophyseal cells induced by
      intraventricular administration of colchicine to adult rats.
AB  - In order to elucidate whether the gender differences observed in the somatotropic
      cells of adult rats are mediated by hypothalamic neuropeptides, a morphometric
      analysis was made of the GH-immunoreactive cells of adult rats treated
      intraventricularly with colchicine. The morphometric and morphological findings
      obtained were correlated to the basal serum levels of GH at the time of
      sacrifice. Treatment with colchicine was seen to increase serum GH levels; this
      increase was accompanied by an increase in the intensity of the reaction of the
      GH-cells and, morphometrically, an increase in their size due to an increase in
      the nuclear area, but with no significant changes in the cytoplasmic area. The
      results suggest that in the absence of somatostatin and GRF the basal release of
      GH is elevated in a similar fashion in both sexes, in turn suggesting that
      gonadal steroids might act at hypothalamic level on the release of somatostatin
      and, indirectly, on the intracellular pool of GH and hormonal secretion.

PMID- 1360851
TI  - 13th International Symposium on Growth and Growth Disorders. 1st International
      Workshop on Growth Hormone Insensitivity. Proceedings. The Netherlands, April
      1992.

PMID- 1360850
TI  - Localization of serotonin, cholecystokinin and somatostatin immunoreactivity in
      the lower respiratory tract of embryonic, foetal and postnatal sheep.
AB  - The lower respiratory tract of the sheep was studied by light-microscopical
      immunocytochemistry for serotonin, cholecystokinin, somatostatin, bombesin and
      calcitonin during different periods of lung development; embryonic, foetal and
      postnatal. At embryonic period only intraepithelial serotonin-containing cells as
      solitary neuroendocrine cells (NEC) and neuroepithelial bodies (NEB) were found.
      At foetal stages, immunoreactive cells to serotonin, cholecystokinin and
      somatostatin were observed in airway epithelium, as solitary NEC and NEBs, and in
      autonomic intrapulmonary ganglia as single or clusters of small intensely
      fluorescent (SIF) cells. In postnatal sheep, serotonin- and cholecystokinin
      containing cells were found within airway mucosa as solitary NECs and NEBs. No
      immunoreactive cells were observed with antiserum to bombesin and calcitonin.
      Quantitative studies showed that serotonin was the predominant substance, and
      that solitary neuroendocrine cells were more numerous in distal conducting
      airways and at foetal stages.

PMID- 1360852
TI  - New genetic findings in old syndromes.

PMID- 1360853
TI  - Neisserial surface variation: how and why?
AB  - Neisseria gonorrhoeae exhibits striking variability in several of its surface
      components (pili, Opa proteins and lipooligosaccharide) in vivo and in vitro.
      Such flagrant variation of this mucosal pathogen's surface components contrasts
      sharply with changes in single surface components of blood-borne trypanosomes and
      borreliae. Despite these differences, similar molecular events are sometimes
      involved.

PMID- 1360854
TI  - Voyage into the future through nursing research.

PMID- 1360855
TI  - Paradoxical bronchoconstriction in asthmatic patients after salmeterol by metered
      dose inhaler.

PMID- 1360857
TI  - [The dose-dependent effect of mezaton and fetanol on the glucose level of the
      blood].
AB  - Experiments with mice and rabbits have revealed that mezaton and fetanol in a
      dose of 0.1 mg/kg are able to cause heterodirectional changes in blood glucose
      levels. When their dose is increased to 1 and 10 mg/kg, the two agents result in
      hyperglycemia.

PMID- 1360856
TI  - [The serotonin- and dopaminergic mechanisms in the action of 1-pyrimidinyl
      piperazine derivatives].
AB  - It has been established in experiments on spinal ganglia neurons of rats that 1
      pyrimidinyl-piperazine derivatives show the properties of partial agonists of 5
      HT1A-receptors. Some of them were discovered to be capable of blocking D2
      dopamine receptors. Comparison of neuronal and behavioral activity of the
      substances tested has demonstrated that their anxiolytic activity detectable
      under the conditions of the conflict situation method significantly correlates
      with 5-HT1A-mimetic and anti-dopamine activity. The latter one correlates well
      with the influence of the substances tested on the time of immobilization in the
      forced swimming test.

PMID- 1360858
TI  - [The effect of narcotic analgesics on nociceptive reactions of a visceral and
      somatic nature].
AB  - The experiments on conscious cats showed that buprenorphine given in 0.0125 and
      0.025 mg/kg selectively inhibited motor, emotional and hemodynamic manifestations
      of pain induced by stimulation of the splanchnic nerve. The analgetic effect of
      morphine, tramal, pentazocine and butorphanol was equally demonstrated on
      visceral and somatic pain models, but the drugs elevated the baseline blood
      pressure and produced no (morphine, pentazocine) or moderate (tramal,
      butorphanol) antihypertensive effects in various nociceptive stimuli.

PMID- 1360859
TI  - Clinical case conference: asystole following anesthesia induction.

PMID- 1360860
TI  - Continuous subcutaneous beta-agonists in asthma.

PMID- 1360861
TI  - Effect of sulphasalazine on antibody response to oral antigen.
AB  - Cholera toxin was orally administered to mice concurrently receiving
      sulphasalazine (SASP) dissolved in L-lysine, or a control substance (L-lysine
      alone). Circulating antibodies to cholera toxin of IgM, IgG and IgA class were
      determined by direct ELISA at day 7, 14, 21 and 28. Although both groups made a
      significant antibody response to the antigen, mice receiving SASP tended to
      produce lower levels. These were significant for IgA on day 21 (P = 0.013), and
      for days 7-28 (P = 0.009), and 14-28 (P = 0.007). Overall, considering all
      antibody classes together from day 7 to 28, there was a significant effect in the
      SASP treated group (P = < 0.04). It appears that SASP exerts a mild
      immunomodulatory effect on the mucosal immune system. Further work is obviously
      required to substantiate these findings. The effect on the gut mucosal immune
      system of a drug known to ameliorate rheumatoid arthritis may offer an insight
      into the aetiopathogenesis of this disease.

PMID- 1360862
TI  - Genetically epilepsy-prone rats have increased brain regional activity of an
      enzyme which liberates glutamate from N-acetyl-aspartyl-glutamate.
AB  - N-Acetylated-alpha-linked acidic dipeptidase (NAALADase) is a membrane-bound
      peptidase which hydrolyzes the endogenous neuropeptide N-acetylaspartylglutamate
      (NAAG) to N-acetylaspartate (NAA) and the excitatory amino acid, glutamate (Glu).
      Although there is evidence that NAAG might be a neurotransmitter, this dipeptide
      could also function as a precursor form of Glu, which is liberated by the
      dipeptidase. We found that the activity of this NAAG hydrolyzing enzyme in
      genetically epilepsy-prone rats was 11-26% greater than control in brain regions,
      including the amygdala, hippocampus and cerebellum, as well as the pyriform,
      entorhinal and frontal cortices. This is consistent with possible increased
      availability of Glu in certain CNS synapses in these rats, which are reported to
      have increased susceptibility to audiogenically, electrically and chemically
      induced convulsions.

PMID- 1360863
TI  - Consequences of an intrastriatal injection of kainic acid on the dopaminergic
      neuronal and vesicular uptake systems.
AB  - Intrastriatal kainic acid injection destroys the neurons originating from the
      striatum, including those on which terminals of the nigro- and meso-striatal
      dopaminergic neurons project. We have studied at various times the consequences
      of this lesion on dopamine metabolism and on the neuronal and vesicular
      transporters. Two and 15 days after kainic acid injection, whereas dopamine
      turnover was increased and the dopamine content unchanged, there was no
      modification in the binding of [3H]GBR 12783, a marker of the neuronal uptake
      complex, but the binding of [3H]dihydrotetrabenazine, a marker of the vesicular
      transporter, was significantly decreased. At later times (30 and 60 days) when
      the dopamine turnover was decreased as well as the dopamine content, the binding
      of [3H]dihydrotetrabenazine was more dramatically decreased (about 30% of
      controls) than that of [3H]GBR 12783. In addition autoradiography showed an
      increase in the density of [3H]dihydrotetrabenazine binding sites in the
      substantia nigra. Thus it appears that the long-term (60 days) repercussions of a
      kainic acid lesion affect simultaneously the dopamine turnover (which is
      decreased) and the vesicular transporter whereas the dopamine uptake complex is
      little affected.

PMID- 1360864
TI  - Effects of ethanol on Na(+)-dependent amino acid uptake: dependence on rat age
      and Na+, K(+)-ATPase activity.
AB  - Acute effects of ethanol on Na(+)-dependent transport of gamma-aminobutyric acid
      (GABA) and glutamic acid (GLU) were investigated in crude synaptosomal
      preparations from rat cerebral cortex. In experiments with 30-40-day-old
      (peripubertal) rats, the overall dose responses of the GABA and GLU transport
      systems to ethanol were biphasic. Stimulation was observed at ethanol
      concentrations (40-160 mM) relevant to intoxication. Inhibition was observed at
      higher concentrations of ethanol. The stimulatory phase of the dose response was
      not observed in 60-100-day-old (adult) rats. In preparations from peripubertal
      rats, other alcohols also had biphasic dose response curves with stimulation at
      low alcohol concentrations. The relative efficacy of the different alcohols
      appeared to correlate with the relative membrane-buffer partition coefficient. In
      synaptosomal membrane vesicles, where artificial ion concentration gradients
      rather than Na+,K(+)-ATPase activity provide the driving force for uptake,
      ethanol did not stimulate GABA uptake. In direct measures of Na+,K(+)-ATPase
      activity, both Rb+ uptake and ATP hydrolysis were enhanced by 80 mM ethanol. We
      conclude that stimulation of Na(+)-dependent uptake of amino acids by ethanol was
      secondary to enhanced Na+,K(+)-ATPase activity and may be associated with a
      specific developmental stage in the rat.

PMID- 1360865
TI  - A voltage-clamp analysis of NMDA-induced responses on dopaminergic neurons of the
      rat substantia nigra zona compacta and ventral tegmental area.
AB  - The effects of NMDA-receptor activation on dopaminergic neurons of the rat
      substantia nigra zona compacta and ventral tegmental area were studied by using
      in vitro intracellular electrophysiological recordings (current and voltage
      clamp). NMDA depolarized the membrane and increased the firing activity. A
      voltage-dependent inward current and a reduction of the apparent input
      conductance were observed in voltage-clamp experiments. Interestingly, the peak
      amplitude of the inward current occurred at approximately -60 mV. The NMDA
      induced responses were reduced by the application of DL-2-amino-5
      phosphonovaleric acid (APV). The NMDA-induced current was unaffected by potassium
      channel blockers, was present in low-sodium solutions or in solutions treated
      with TTX; but was reduced or blocked in low-calcium solutions containing cobalt.
      In addition, no reduction of the apparent input conductance was observed either
      in the solutions without magnesium or in those with low-sodium. Our data indicate
      that the activation of NMDA receptors produces a powerful excitatory stimulus on
      the dopaminergic neurons of the ventral mesencephalon and this may be primarily
      the result of a voltage-dependent influx of calcium ions. The degeneration of the
      dopaminergic cells after application of neurotoxins may be explained by their
      peculiar response to NMDA.

PMID- 1360866
TI  - Spermine facilitates the generation of long-term potentiation of evoked potential
      in the dentate gyrus of anesthetized rats.
AB  - The effects of the polyamines, spermine, spermidine and putrescine, on long-term
      potentiation (LTP) of evoked potential were investigated in the dentate gyrus of
      anesthetized rats. Injection of 5 nmol spermine into the lateral ventricle did
      not influence the basal amplitude of the population spike, but significantly
      enhanced the potentiation induced by subthreshold tetanic stimulation (20 pulses
      at 60 Hz). The effect of spermine resulted in facilitation of LTP generation.
      Injection of the same dose of spermidine or putrescine affected neither the basal
      response nor the potentiation induced by subthreshold tetanus at all, indicating
      that the LTP-facilitating effect is specific to spermine. Furthermore, the LTP
      facilitating effect of spermine was dose-dependent in the range of 0.5-50 nmol.
      When 5 nmol ifenprodil, an antagonist at the polyamine site of the NMDA receptor
      channel complex, was concomitantly injected, spermine could not facilitate the
      generation of LTP. Since injection of ifenprodil alone did not influence the
      generation of LTP, it is probable that ifenprodil specifically blocks the effect
      of spermine. These results suggest that spermine facilitates the generation of
      hippocampal LTP, probably through an ifenprodil-sensitive polyamine site
      associated with the NMDA receptor.

PMID- 1360867
TI  - Potent antinociceptive effects of clonidine systemically administered in an
      experimental model of clinical pain, the arthritic rat.
AB  - The effects of various doses of the alpha-2 adrenoceptor agonist clonidine
      administered systemically (30, 50 and 100 micrograms/kg i.v.), were investigated
      on the vocalization threshold to paw pressure in normal rats and in rats with
      Freund's adjuvant-induced arthritis. Previous results have suggested that there
      is an increase in the activity of the bulbospinal noradrenergic systems in these
      arthritic animals. In the present study, clonidine led to significant
      antinociceptive effects in both groups of rats. Clonidine was found to be highly
      effective in arthritic animals, even at the lower concentration: the elevation in
      threshold produced by 30 micrograms/kg i.v. was 160% in arthritic vs. 124% in
      normal rats. The effects of clonidine were prevented dose-dependently by
      pretreatment with yohimbine or idazoxan 250 to 1000 micrograms/kg i.v., in the
      two groups of rats, indicating clearly that the dose-dependent effects of i.v.
      clonidine are mediated by alpha-2 adrenoceptors.

PMID- 1360869
TI  - Chromosome 21 rearrangement in acute biphenotypic leukemia.
AB  - A patient with myelodysplastic syndrome (MDS) and a 47,XY,+21 karyotype at
      diagnosis, was documented to have a clonal chromosome 21 rearrangement, i(21q),
      four months before transformation to acute biphenotypic leukemia. For 4 months
      after transformation, isochromosome 21 persisted while the patient was receiving
      treatment with zidovudine. Vitamin D3 was added to zidovudine for an additional
      month, during which time the trisomy 21 clone reappeared as the predominant cell
      population. The unique aspects of this patient are the atypical evolution of
      chromosome 21, the transformation to biphenotypic leukemia, and the occurrence of
      i(21q) associated with biphenotypic leukemia evolving from an MDS.

PMID- 1360868
TI  - Characterization of phencyclidine-induced effects on neuropeptide Y systems in
      the rat caudate-putamen.
AB  - Multiple administrations of the psychotomimetic drug, phencyclidine-HCI (PCP),
      decreased striatal neuropeptide Y-like immunoreactivity (NPY-LI) levels in a dose
      dependent manner. Single or multiple PCP administrations decreased striatal NPY
      levels after 10-12 h; levels returned to control 24 h after a single dose or 58 h
      after multiple doses. In contrast, no significant changes were seen in nigral NPY
      levels with either acute or multiple-dose PCP treatments. The role of monoamine,
      sigma or opioid receptors in PCP-induced striatal NPY changes was evaluated. When
      administered alone, the alpha 1-adrenergic antagonist, prazosin, the sigma
      antagonist, BMY 14802, and the dopamine D2 antagonist, sulpiride decreased
      striatal NPY levels; however, only prazosin and the dopamine D1 antagonist, SCH
      23390, significantly attenuated PCP-induced changes. Administration of the gamma
      aminobutyric acid transaminase (GABA-T) inhibitors, amino-oxyacetic acid (AOAA)
      or gamma-vinyl-GABA (GVG, vigabatrin, MDL 71,754) alone had no effect on striatal
      NPY-LI levels while administration of these indirect GABA agonists prior to or
      concurrently with PCP treatment completely blocked PCP-induced changes in
      striatal NPY-LI levels. The effect of the non-competitive N-methyl-D-aspartate
      (NMDA) receptor antagonist, MK-801, on striatal NPY-LI content resembled that of
      PCP and was also blocked by the two indirect GABA agonists. These data suggest
      that NPY systems are modulated by glutamatergic activity (specifically by the
      NMDA receptor) and that the interaction between these two transmitter systems is
      mediated by GABAergic mechanisms.

PMID- 1360870
TI  - Allelic loss from chromosome 11 in parathyroid tumors.
AB  - Parathyroid tumors may occur in a sporadic fashion or, more rarely, as part of a
      familial syndrome (such as familial multiple endocrine neoplasia type I). The
      MENI gene has been mapped by linkage analysis to chromosome 11 at band q11-q13,
      and presumably acts as a tumor suppressor gene. In the present study, which is an
      extension of our previous studies, we examined 41 parathyroid tumors from
      patients with familial multiple endocrine neoplasia type I and 61 sporadic
      parathyroid tumors with markers on chromosome 11, to assess the extent of allelic
      loss in those tumors. Twenty-four of the MENI-associated tumors (58%) and 16 of
      the sporadic parathyroid tumors (26%) displayed allelic loss from chromosome 11.
      The region of overlap of the allelic losses in the MENI-associated tumors enables
      us to place the MENI gene between PGA centromerically and INT2 telomerically, a
      region spanning about 7.5 cM. Taken together with locus ordering by linkage
      analysis, this clearly localizes the MENI gene telomeric to the PGA locus. Our
      inability to detect allelic loss on chromosome 11 in some parathyroid tumors
      suggests the existence of other genes involved in the development and/or
      progression of this subgroup of presumably monoclonal tumors; or that localized
      events involving the 11q tumor suppressor gene have occurred in some parathyroid
      tumors whose detection is beyond the sensitivity of our analysis; or that at
      least some of the specimens analyzed were in fact primarily hyperplastic
      parathyroid tissue.

PMID- 1360871
TI  - Histogenetic analysis of ovarian germ cell tumors by DNA fingerprinting.
AB  - The histogenesis of ovarian germ cell tumors (11 mature teratomas, three
      malignant transformations of mature teratomas, two immature teratomas, and four
      dysgerminomas) was investigated genetically using minisatellite DNA probes 33.15
      and 33.6 for person-specific restriction fragment length polymorphism (DNA
      fingerprint) analysis. The DNA fingerprints of six ovarian teratomas were
      identical with those of mononuclear cells from each host, while some polymorphic
      bands observed in the host mononuclear cells were lost in the DNA fingerprints of
      the other five cases. The cases of malignant transformation of mature teratoma
      and immature teratoma showed that some polymorphic bands of DNA fingerprints from
      the host mononuclear cells were absent in the tumor tissues. In four cases with
      dysgerminomas, the DNA fingerprints of tumors were completely identical with
      those of the respective host mononuclear cells. The present results suggest that
      mature cystic teratomas of the ovary arise from germ cells arrested at various
      stages of meiosis, while immature teratomas are derived from postmeiotic germ
      cells. Malignant transformation may occur exclusively in the mature teratomas
      arising from postmeiotic germ cells. Dysgerminomas develop from premeiotic
      oogonia (primordial germ cells). Thus, DNA fingerprints are a useful and
      sensitive tool for identifying the pathogenesis of germ cell tumours.

PMID- 1360872
TI  - In vitro cytotoxic targeting by human mononuclear cells and bispecific antibody
      2B1, recognizing c-erbB-2 protooncogene product and Fc gamma receptor III.
AB  - Bispecific murine monoclonal antibody 2B1, possessing dual specificity for the
      human c-erbB-2 protooncogene product and human Fc gamma receptor III (CD16) was
      evaluated for the ability to promote specific lysis of c-erbB-2-positive tumor
      cells in vitro. In short-term 51Cr release assays with human mononuclear cells as
      effectors and SK-Br-3 human breast cancer cells as targets, neither parental
      antibody of 2B1 mediated significant specific lysis, but bispecific antibody was
      as active as a chemical heteroconjugate, with 5 ng/ml of 2B1 causing half-maximal
      lysis at an effector/target ratio of 20:1 and 2 ng/ml 2B1 causing half-maximal
      lysis at an E/T ratio of 40:1. The cytotoxic targeting activity of 2B1 F(ab')2
      fragment was the same as that of whole bispecific antibody, and the activity of
      whole 2B1 was not reduced when assays were performed in 100% autologous human
      serum, indicating that 2B1 binds effector cells through the CD16-binding site
      derived from parental antibody 3G8 rather than through its Fc portion. Variable
      inhibition of 2B1-mediated lysis was observed when autologous polymorphonuclear
      leukocytes from different donors were added to mononuclear effector cells at a
      2:1 ratio; this inhibition was overcome at higher antibody concentration. 2B1
      bispecific monoclonal antibody was also able to mediate targeted cytolysis using
      whole human blood as a source of effector cells or using effector or target cells
      derived from ovarian cancer patients.

PMID- 1360873
TI  - Expression and functional activity of P-glycoprotein in cultured cerebral
      capillary endothelial cells.
AB  - Analysis of a panel of endothelial cells passaged between 5 and 25 times and
      derived from various organs and species demonstrated that murine and porcine
      cerebral capillary endothelial cells actively excluded the fluorescent dye
      rhodamine 123, a substrate of P-glycoprotein. In addition, rhodamine 123
      accumulation could be enhanced by the multidrug resistance chemosensitizer
      verapamil, known to reduce P-glycoprotein-mediated drug efflux. Cloned murine and
      porcine cerebral capillary endothelial cells were immunoreactive with the C219
      monoclonal antibody to P-glycoprotein, and a C219 epitope-specific blocking
      peptide could abolish staining. The antiproliferative and cytotoxic effects of
      vincristine, but not cis-platinum(II) diamminedichloride, were increased by the
      addition of either verapamil or cyclosporin A to brain endothelial cell cultures
      in a 72-h assay, as determined by [3H]thymidine incorporation and total protein
      measurement. Cyclosporin A was a more effective reversal agent than verapamil.
      Thus, a P-glycoprotein isoform may be constitutively expressed in brain
      endothelial cells in vitro and supports the available data on in situ
      immunohistochemical staining of P-glycoprotein at the blood-brain barrier. In
      addition, these findings may indicate that one function of P-glycoprotein in vivo
      at the blood-brain barrier is the exclusion of xenobiotics from central nervous
      system tissues.

PMID- 1360874
TI  - Homeotic transformations in the mouse induced by overexpression of a human Hox3.3
      transgene.
AB  - A permanent transgenic mouse line was generated carrying 40 copies of the human
      Hox3.3 gene. The resulting mice express large amounts of Hox3.3 protein in
      posterior regions of the embryo where this homeodomain protein is normally not
      expressed. The transgene causes homeotic transformations of the skeleton, in
      particular the appearance of an extra pair of ribs in the lumbar region,
      transformation of the shape of posterior ribs into that of more anterior ones,
      and the joining of an additional pair of ribs to the sternum. The phenotype of
      this line resembles that obtained by the targeted loss-of-function mutation of
      Hox3.1 (Le Mouellic et al., 1992). In transient assays, the human Hox3.3
      transgene leads to the formation of additional ribs in more posterior vertebrae
      as well.

PMID- 1360875
TI  - Altering the boundaries of Hox3.1 expression: evidence for antipodal gene
      regulation.
AB  - To investigate the function of region-specific patterns of mouse homeobox gene
      expression during embryogenesis, we programmed a minimal change in the
      distribution of Hox3.1 transcripts along the anteroposterior body axis in
      transgenic mice. Regulatory sequences from Hox1.4, a gene normally expressed more
      anteriorly than Hox3.1, were chosen to direct expression of a Hox3.1 transgene.
      Offspring of independent transgenic lines expressed the transgene more anteriorly
      than the Hox3.1 gene. Rather than predicted posterior transformations, we
      observed anterior transformations of vertebrae in newborn mice. Transgenic mice
      also developed profound gastrointestinal tissue malformations, which may provide
      a molecular explanation for human developmental disorders often involving these
      same two regions. Paradoxically, vertebral transformations in the transgenic mice
      were strikingly similar to those reported in mice homozygous for a null mutation
      of the Hox3.1 gene. This observation suggests that Hox genes may be regulated
      antipodally, with over- or underexpression resulting in similar phenotypes.

PMID- 1360877
TI  - The 2nd International Symposium on Treatment of Liver Cancer. Taipei, Taiwan, 3-4
      February 1991.

PMID- 1360878
TI  - Missense mutations of the tissue-nonspecific alkaline phosphatase gene in
      hypophosphatasia.
AB  - Hypophosphatasia is an inborn error of metabolism that is characterized
      clinically by defective bone mineralization and biochemically by deficient
      activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP) in
      serum and in tissues. Clinical severity is extremely variable, ranging from death
      in utero to pathologic fractures first presenting in adulthood. Severe forms of
      the disease are inherited in an autosomal recessive fashion; the modes of
      transmission of mild forms are uncertain. Deficiency of TNSALP activity in this
      condition suggests that mutations in the TNSALP "candidate" gene are the primary
      defects. This hypothesis was supported in 1988 by the demonstration, in one
      inbred infant, that an identical missense mutation in both alleles of the gene
      encoding TNSALP caused lethal hypophosphatasia. Here we summarize the work
      leading to that discovery and discuss the recent identification of additional
      missense mutations in the TNSALP gene associated with the entire clinical
      spectrum of hypophosphatasia.

PMID- 1360876
TI  - Doxorubicin sensitivity pattern in a panel of small-cell lung-cancer cell lines:
      correlation to etoposide and vincristine sensitivity and inverse correlation to
      carmustine sensitivity.
AB  - The aim of our investigations is to evaluate whether the sensitivity patterns of
      small-cell lung-cancer (SCLC) cell lines in vitro can be used in evaluating new
      drugs and in selecting drugs for the optimization of combination therapy. In our
      attempts to obtain a panel of cell lines demonstrating differential patterns in
      sensitivity, we have developed three SCLC lines exhibiting different types of
      multidrug resistance (MDR). In the present investigations we compared the
      sensitivity patterns shown by five wild-type SCLC lines and three MDR lines in
      response to six different types of drugs: doxorubicin, cytarabine, carmustine,
      cisplatin, vincristine, and etoposide. In the wild-type SCLC cell lines, the
      range of variation in sensitivity to all drugs was within a factor of 10. Cell
      lines showing low sensitivity to doxorubicin also exhibited low sensitivity to
      etoposide and vincristine, and vice versa. In contrast, the pattern of
      sensitivity to carmustine was almost the opposite of that to doxorubicin. A
      tendency to an inverse relationship between doxorubicin and carmustine
      sensitivity was also observed when doxorubicin sensitivity was reduced in near
      stationary cells and in cells exposed to the metabolic inhibitor 2-deoxy-D
      glucose. In agreement with the pattern observed for the wild-type lines, all of
      the MDR sublines demonstrated collateral sensitivity to carmustine. As to
      cytarabine, the wild-type lines expressed a sensitivity pattern similar to that
      shown in response to doxorubicin. Interestingly, the opposite pattern was found
      in the MDR lines, as all three demonstrated cytarabine hypersensitivity. The
      combination of alkylating agents and "MDR" drugs are of proven clinical benefit
      in the treatment of solid tumors, as is the combination of anthracycline and
      cytarabine in acute myeloid leukemia. The experimentally derived sensitivity data
      on cytarabine, alkylating agents, and MDR drugs (i.e., etoposide, doxorubicin,
      vincristine) thus resemble the clinical experience with these drugs, and we
      conclude that the use of a clonogenic assay on the described panel of SCLC cell
      lines can give valuable information for the selection of agents for combination
      therapy.

PMID- 1360879
TI  - CD4-independent binding of HIV-1 to the B lymphocyte receptor CR2 (CD21) in the
      presence of complement and antibody.
AB  - Complement and antibody contribute to infection-enhancement and possible expanded
      cellular tropism of HIV-1 in vitro through a process requiring complement
      receptors. Until now, however, the ability of HIV-1 to bind complement receptors
      has not been documented or characterized. We investigated whether antibody and
      complement permitted HIV-1 to bind to the B lymphocyte receptor, CR2 (CD21), in
      an effort to learn more about infection-enhancement, and also because CR2 can
      mediate B cell proliferation and antigen localization in lymphoid organs in other
      systems. HIV-1 incubated with antibody and fresh human serum as a source of
      complement bound approximately 10-fold greater to cells expressing CR2 than to
      HIV-1-permissive cells lacking this receptor. A similar effect was observed using
      cells which expressed CR2 but no CD4. This binding was minimal in heat
      inactivated and C3-deficient sera, and was significantly reduced by the anti-CR2
      MoAb, OKB7, but not by the anti-CD4 MoAb, OKT4a. Thus, complement and antibody
      acted in concert to facilitate the binding of HIV-1 to CR2 independently of CD4.
      CD4-independent binding of HIV-1 to CR2 was not sufficient to produce infection
      in Raji-3 cells. Titres of antibodies mediating CR2 binding correlated with
      antibody titres as measured by immunofluorescence (P < 0.01) and infection
      enhancement (P < 0.05) but were discordant with titres of neutralizing
      antibodies, a result consistent with the utilization of CR2 for enhanced
      infection of cells. The ability of complement and antibody to facilitate the
      binding of HIV-1 to CR2 in the absence of CD4 provides new insights into
      mechanisms of HIV-1-induced immunopathogenesis and infection-enhancement.

PMID- 1360880
TI  - Haemorrhage-induced alterations in function and cytokine production of T cells
      and T cell subpopulations.
AB  - Haemorrhage produces alterations in macrophage, T and B cell function. In order
      to better define the mechanism for the effects of blood loss on immune response,
      we examined function of and cytokine production by purified T cells, CD4+ and
      CD8+ subpopulations after blood loss. Whereas T and CD4+ cells from control,
      unhaemorrhaged animals produced no alteration in proliferation when added to
      cultures of mitogen-stimulated splenocytes from normal mice, proliferation was
      decreased when T or CD4+ cells from haemorrhaged mice were included. The addition
      of CD8+ cells from haemorrhaged animals to mitogen-stimulated cultures reduced
      proliferation by approximately 50% more than that found when CD8+ cells from
      control, unhaemorrhaged animals were included. Supernatants of mitogen-stimulated
      splenocytes from haemorrhaged mice contained significantly less IL-2 and
      interferon-gamma (IFN-gamma) than did those from control, unhaemorrhaged mice.
      CD4+ populations from haemorrhaged mice produced significantly more IL-10, and
      significantly less IFN-gamma, than did CD4+ cells from control, unhaemorrhaged
      mice. There were no significant differences in IL-2, IL-4, IL-10 or IFN-gamma
      production by CD8+ cells from haemorrhaged or control mice. The present
      experiments demonstrate that haemorrhage affects both CD4+ and CD8+ T cell
      subsets. In particular, haemorrhage appeared to activate CD4+, Th2 cells, with
      concomitant suppression of the Th1 subpopulation. These results provide a
      mechanism which may contribute to the alterations in cytokine production
      previously described to occur following blood loss.

PMID- 1360882
TI  - Hypercholesterolemia: An Evolving Risk Factor. Satellite symposium at the 9th
      International Society of Atherosclerosis Meeting. Chicago, Illinois, October 7,
      1991.

PMID- 1360881
TI  - Expression and gene transcript of Fc receptors for IgG, HLA class II antigens and
      Langerhans cells in human cervico-vaginal epithelium.
AB  - The mechanism of transmission of HIV from the male to the female genital tract or
      in the reverse order is not clear. CD4 glycoprotein is the receptor for HIV and
      Langerhans cells and the related dendritic cells could play a role in the initial
      transmission of HIV. Fc receptors (FcR) for IgG might be involved in antibody
      mediated binding of HIV. We carried out an immunohistological study of normal
      human cervical and vaginal epithelia for the presence of CD4 glycoprotein,
      Langerhans cells and FcR to IgG. CD4+ glycoprotein was not found in the vaginal
      or cervical epithelium, with the exception of a few endocervical epithelial
      cells. A small number of CD4+ mononuclear cells were found in the endocervical
      epithelium of a third of the specimens but a large number of CD4+ cells was found
      in the submucosa of most of the cervical and vaginal specimens. Langerhans cells
      expressing CD4, HLA class II, Fc gamma R2 and Fc gamma R3 were detected in most
      vaginal, ectocervical and transformation zone epithelia and in 9/14 endocervical
      tissues. Fc gamma R3 was detected in about two-thirds of the columnar
      endocervical epithelium and the transformation zone. A smaller number of
      specimens expressed Fc gamma R2 in these epithelia, but Fc gamma R1 was not
      detected. We then demonstrated mRNA for Fc gamma R3 in the columnar endocervical
      epithelial cells and transformation zone by in situ hybridization, using a CD16
      RNA probe. Fc gamma R3 and Fc gamma R2 gene transcripts were also found in fetal
      cervical tissue by applying the polymerase chain reaction to amplify portions of
      the Fc gamma R3 and Fc gamma R2 coding sequences in cDNA prepared from fetal RNA.
      HLA-DR was found in the endocervical cells, transformation zone and in Langerhans
      cells of all specimens. The presence of Langerhans cells, Fc gamma receptors and
      HLA class II antigen offers three potential mechanisms for cervico-vaginal HIV
      transmission: (i) direct HIV infection of Langerhans cells, (ii) binding of HIV
      antibody complexes to cervical epithelial Fc gamma receptors and (iii) binding of
      HIV infected CD4+ cells to cervical HLA class II antigen which may infect these
      or the adjacent CD4+ cells.

PMID- 1360885
TI  - Proceedings of the Congress of Neurological Surgeons. Orlando, Florida, October
      26-31, 1991.

PMID- 1360884
TI  - WHO/IUIS Standardization Programme.

PMID- 1360883
TI  - Accessory molecules expressed on the peripheral blood or synovial fluid T
      lymphocytes from patients with Sjogren's syndrome or rheumatoid arthritis.
AB  - We previously demonstrated that the cells expressed by activation antigens were
      increased in several T cell subsets from the peripheral blood (PB) and joint
      fluid (JF) of patients with Sjogren's syndrome (SS) or rheumatoid arthritis (RA).
      In the present report, we further determined by three-color flow cytometry the
      homing receptors (Leu8) for peripheral lymph nodes expressed on naive (CD45RA+)
      or memory (CD45RA-) CD4+ cells and on the two subsets of CD8+ cells (CD11b+ and
      CD11b-) in the PB and JF from SS and RA patients. In addition, the activation
      antigens (HLA-DR) and two adhesion molecules, including the alpha-chain of the
      leukocyte function associated antigen-1 (LFA 1 alpha: CD11a) and its ligand
      (intercellular adhesion molecule-1: ICAM-1: CD54) expressed on T cells, were
      compared. We found that CD45RA-CD4+ cells were markedly increased in JF, while
      CD45RA+CD4+ cells were almost absent. Leu8+ cells were decreased in both CD45RA
      CD4+ and CD8+CD11b-cells (cytotoxic T cells) in the JF, and were also decreased
      in the CD8+CD11b-subset in the patients' PB. Furthermore, activated (DR+) T cells
      were markedly increased in JF, and the cells expressed more adhesion molecules in
      both the PB and JF from patients, compared with the DR-T cells. The DR+ T cells
      therefore are considered to be memory T cells, which are more efficient for cell
      to-cell interactions. These observations also suggest that the Leu8- and DR+ T
      cells with increased adhesion molecules might preferentially migrate into
      inflammatory tissues, and that naive T cells are being further converted to to
      memory T cells by in vivo stimulation within the tissues.

PMID- 1360886
TI  - Neurosurgery, molecular medicine, and the Pandora-Panacea continuum: future
      implications for glioma therapy?

PMID- 1360887
TI  - New insights and technologies in brain grafting.
AB  - Significant progress has been made in the field of brain grafting over the last
      15 years. Neurosurgeons have been involved directly in the preclinical and
      clinical efforts in this fascinating and promising field, along with their
      neuroscience colleagues. Through a better understanding of the complex mechanisms
      involved in response to transplants in the brain, new technologies and
      experimental strategies are being developed to improve the safety and efficacy of
      these procedures. The time is right for carrying out appropriate preclinical
      studies in rodents and nonhuman primates to answer one of the most basic
      questions: Is a tissue graft necessary for behavior improvement in degenerative
      diseases such as PD, HD, or AD? With available tools and technology and an open
      mind to new ideas, brain grafting has a tremendous potential in the
      neurosurgeon's armamentarium, both today and in the future.

PMID- 1360888
TI  - Allele loss on chromosome 11p is associated with poor survival in ovarian cancer.
AB  - RFLP (restriction fragment length polymorphism) analysis in 46 ovarian tumour and
      paired blood samples shows that 33 per cent (5/15) of informative carcinomas had
      loss of heterozygosity (LOH) at 11p15.4 (Calcitonin locus) and 18% (4/22) had LOH
      at 11p15.5 (Ha-ras). No LOH was detected in five borderline and four benign
      ovarian tumours. Analysis of survival in the carcinoma group (37 patients) showed
      a significantly poorer survival in patients whose tumours showed LOH at either or
      both of these 11p loci (chi 2 = 7.771, p = 0.005). This suggests the presence of
      a tumour suppressor gene (tsg) on the short arm of chromosome 11 whose loss is
      associated with particularly aggressive disease.

PMID- 1360890
TI  - Systemic lupus erythematosus: renal vasculitis. 2nd Seminar on Renal Involvement
      in Systemic Vasculitis. Vimercate, September 21, 1991.

PMID- 1360889
TI  - Demonstration of calf abnormalities by magnetic resonance imaging in
      polyarteritis nodosa.
AB  - A 36-year-old Caucasian woman presenting with persisting painful calves after a
      flu-like illness was diagnosed as having polyarteritis nodosa. Magnetic resonance
      imaging of the lower legs showed abnormal signal intensity of the outer muscle
      groups with sparing of the central located muscles. The good clinical response to
      oral prednisone was supported by improvement of MRI.

PMID- 1360891
TI  - Intercellular adhesion molecule-1 as a marker of activity in lupus nephropathy.

PMID- 1360892
TI  - The Fifth National Conference of the Biliary Surgery Section of the Chinese
      Surgical Society.

PMID- 1360893
TI  - Electrophoresis Forum '92. Proceedings of the International Meeting. Munich,
      October 26-28, 1992.

PMID- 1360894
TI  - Temperature-gradient gel electrophoresis for the detection of polymorphic DNA and
      for quantitative polymerase chain reaction.
AB  - In order to detect mutations in a gene, either known mutations from human
      diseases or artificial ones in transgenic animals, or to screen for not yet
      identified mutations in patients, a method is required which guarantees detection
      of mutations which might occur in every single position of the whole open reading
      frame (ORF). It will be shown that a combination of polymerase chain reaction
      (PCR) and temperature gradient gel electrophoresis (TOGE) fulfills these
      requirements. By thermodynamic calculations the shift in the gel electrophoresis
      due to a mutation can be calculated in dependence on the position of the
      mutation. The theoretical results were tested with the mutations known so far.
      The quantitative determination of the copy number of a specific DNA or RNA
      sequence in a biological specimen (quantitative PCR) can be performed precisely
      and easily by combining PCR and TGGE. The system uses a quantification strategy
      of a new type of internal standardization. TGGE is applied to separate homo- and
      heteroduplexes which correspond respectively to standard and template sequences.
      The accuracy of this quantification strategy is very high, with a variability of
      < 15%. In addition to quantification, PCR/TGGE detects PCR artifacts and template
      mutants.

PMID- 1360895
TI  - Simple repeats are not found more abundantly at G/C-rich regions.
AB  - Three hundred and fifty cosmids from chromosome 7, previously analyzed for the
      presence of rare-cutting restriction enzyme sites, were analyzed for the presence
      of microsatellite sequences [(CA)n or (CT)n repeats]. Of these, 147 cosmids were
      found to contain at least one (CA)n repeat unit and 51 cosmids contained at least
      one (CT)n repeat unit. No evidence was found for the prevalence of microsatellite
      repeat units in the vicinity of rare-cutter restriction enzyme sites.

PMID- 1360896
TI  - Reversible shutdown of replicon initiation by transient hypoxia in Ehrlich
      ascites cells. Dependence of initiation on short-lived protein.
AB  - The O2-dependent regulation of replication in Ehrlich ascites cells,
      characterized by a reversible shutdown of replicon initiation during hypoxia, was
      scrutinized with respect to the involvement of gene expression. Synchronous and
      asynchronous cells were subjected to transient hypoxia and examined for
      expression of selected 'late' growth-regulated mRNA and for the influence of
      inhibitors of transcription and translation on DNA replication. Irrespective of
      whether replicon initiation was suppressed by hypoxia or retriggered by
      reoxygenation, the levels of thymidine kinase mRNA and of proliferating cell
      nuclear antigen/cyclin mRNA were as high as in untreated replicating cells. The
      level of histone H3.1 mRNA followed, with a distinct delay, the replicative
      activity of the cells governed by the imposed changes of pO2. The response of
      replication to inhibition of transcription and translation was virtually the same
      as to hypoxia, i.e. a selective suppression of replicon initiation. It was
      demonstrated that replicon initiation depends on one or several short-lived
      protein(s) (lifetime about 5 min) which is (are) formed under hypoxic conditions
      as well. The lifetime of the corresponding RNA message(s) is in the range of
      several hours. It is suggested that the expression of genes conditioning resting
      cells for DNA replication remains unaffected by hypoxia or by restoring the
      normal pO2. Hypoxic cell appear to rest in a state fully prepared for entering
      DNA replication, but a yet unknown event essential for replicon initiation is
      blocked. This event depends on a critical oxygen tension as well as on short
      lived protein(s).

PMID- 1360897
TI  - Current concepts in the pathophysiology of hepatic encephalopathy.

PMID- 1360899
TI  - Neuroimmunological Aspects in Rheumatic Diseases. Workshop at the 25th Annual
      Meeting of the European Society of Clinical Investigation. Pisa, Italy, 3-6 April
      1991.

PMID- 1360898
TI  - Severe type III hyperlipoproteinemia associated with unusual apolipoprotein E1
      phenotype and epsilon 1/'null' genotype.
AB  - A 60-year-old white male (KH) was diagnosed to suffer from severe type III
      hyperlipoproteinemia (HLP) and premature cardiovascular disease. Biochemical
      analysis revealed an unusual apolipoprotein (apo) E phenotype and genotype. All
      clinical characteristics of type III HLP were present in the patient. His very
      low density lipoprotein (VLDL) cholesterol to plasma triglyceride (TG) ratio was
      elevated at 0.97 without therapy which is unusually high (normal ratio about
      0.18). By contrast his plasma apo E level was only moderately elevated (6.8 mg dl
      1). The patient's apo E migrated in the apo E1 position on isoelectric focusing
      gels. Chemical modification with cysteamine and treatment with neuraminidase
      confirmed the presence of two cysteine residues in the patient's apo E and a
      normal sialylation pattern. Pedigree analysis suggested that the patient was a
      compound heterozygote with one apo epsilon 1 allele and another allele whose
      product did not appear in the plasma compartment ('null' allele). Direct
      sequencing of polymerase chain reaction (PCR) amplified segments of the apo E
      gene as well as restriction fragment length polymorphism (RFLP) analysis with the
      endonuclease Taq I identified an adenosine for guanosine (G-->A) exchange in the
      second base of codon 127 that is predictive for an Asp for Gly substitution in
      the encoded apo E amino acid sequence. This mutation is the structural basis for
      the apo E1 isoform identified upon isoelectric focusing. Five other family
      members are also carriers of the mutant apo epsilon 1 allele. Two of those were
      hyperlipidemic and exhibited biochemical characteristics of type III HLP. A
      second mutation, a deletion of a G in codon 31, is predictive for a reading
      frameshift that encodes for a premature stop in codon 60. Our inability to
      identify the product of a second apo E allele in the plasma of the patient and
      two other members of the KH family corresponds with the heterozygous presence of
      this mutation in the affected individuals. Both relatives (like the index case)
      had an increased VLDL cholesterol to plasma TG ratio, which indicates the
      presence of cholesterol-enriched VLDL particles. We propose that the single base
      deletion in the apo E gene which is the cause of a non-functional 'null' allele
      in addition to a probably dominant apo E1 (Gly127-->Asp, Arg158-->Cys) variant of
      late or incomplete penetrance are the primary genetic defects in this kindred
      leading to severe dysbetalipoproteinemia.

PMID- 1360900
TI  - Ethacrynic acid-induced convulsions and brain neurotransmitters in mice.
AB  - Intracerebroventricular injection of ethacrynic acid (50% convulsive dose; 50
      micrograms/mouse) accelerated the synthesis/turnover of 5-hydroxytryptamine (5
      HT) but suppressed the synthesis of gamma-aminobutyric acid and acetylcholine in
      mouse brain. These effects were completely antagonized by pretreatment with a
      glutamate/N-methyl-D-aspartate antagonist, aminophosphonovaleric acid. In
      ethacrynic acid-induced convulsions, these neurotransmitter systems may be
      differentially modulated, probably through activation of glutaminergic neurons in
      the brain.

PMID- 1360901
TI  - Effect of 5-HT receptor and adrenoceptor antagonists on micturition in conscious
      cats.
AB  - Micturition was induced in awake cats by infusing saline into the bladder at a
      physiological filling rate. Methysergide, a serotonergic antagonist given
      intrathecally, decreased the volume at which micturition occurred. Phentolamine,
      a non-specific alpha-adrenoceptor antagonist, also decreased volume threshold.
      Prazosin, an alpha 1-adrenoceptor antagonist, was without effect on micturition.
      These results imply that 5-HT receptors and alpha 2-adrenoceptors may be
      inhibitory to micturition at a spinal level.

PMID- 1360902
TI  - Microinjection of S-nitrosocysteine into the nucleus tractus solitarii of
      conscious rats decreases arterial pressure but L-glutamate does not.
AB  - Unilateral microinjection of L-glutamate into the nucleus tractus solitarii of
      conscious rats increased arterial pressure and caused bradycardia while
      microinjection of S-nitrosocysteine into the same site of these animals caused
      hypotension and bradycardia. The responses to S-nitrosocysteine were blocked by
      prior microinjection of methylene blue into the nucleus tractus solitarii. The
      bradycardia and fall in arterial pressure induced by S-nitrosocysteine resemble
      more the cardiovascular changes in response to activation of baroreceptor
      afferents than the bradycardia and increase in arterial pressure induced by
      microinjection of L-glutamate into the nucleus tractus solitarii of conscious
      rats.

PMID- 1360903
TI  - Antagonism of ethanol withdrawal convulsions in Withdrawal Seizure Prone mice by
      diazepam and abecarnil.
AB  - Abecarnil, a beta-carboline acting at benzodiazepine receptors, has been shown to
      have anxiolytic and anticonvulsant properties in a number of models. It has
      reduced muscle relaxant and incoordinating effects in comparison to diazepam.
      Given the wide clinical application of diazepam to prevent alcohol withdrawal
      seizures, a genetic animal model was employed to compare abecarnil with diazepam
      for its anti-withdrawal effects. Withdrawal Seizure Prone (WSP) mice, genetically
      selected to develop severe handling-induced convulsions after withdrawal from
      chronic ethanol treatment, were exposed to ethanol vapor for 24 h. WSP mice given
      doses of abecarnil or diazepam at the peak of withdrawal had significantly
      reduced handling-induced convulsion scores. While abecarnil was slightly more
      potent than diazepam, its effects were shorter-lasting. Similar results were seen
      in an experiment where withdrawal handling-induced convulsions were assessed
      after a single high-dose ethanol injection. Abecarnil and diazepam also reduced
      the smaller handling-induced convulsion scores seen in naive WSP mice. Single
      doses of abecarnil or diazepam did not lead to a rebound elevation of handling
      induced convulsion scores suggestive of a withdrawal reaction.

PMID- 1360904
TI  - Adenylate cyclase from sea urchin eggs is positively and negatively regulated by
      D-1 and D-2 dopamine receptors.
AB  - The adenylate cyclase present in membranes prepared from sea urchin eggs is
      sensitive to dopamine stimulation. The receptor sites coupled to sea urchin
      adenylate cyclase were characterized by means of specific agonists and
      antagonists. The D-1 dopamine agonist SKF-38393 was able to stimulate enzyme
      activity, while the two D-1 dopamine antagonists, SCH-23390 and SKF-83566,
      suppressed the stimulatory effect of dopamine. In addition, the D-2 dopamine
      agonists, PPHT and metergoline, brought about a dose-dependent inhibition of
      dopamine-stimulated adenylate cyclase activity. These data show that: (i) in sea
      urchin eggs adenylate cyclase is regulated by dopamine receptors; (ii) these
      receptors share characteristics with D-1 and D-2 dopamine receptors present in
      the mammalian brain.

PMID- 1360905
TI  - Human Diploid Fibroblast-Like Cells as a Model System for the Study of
      Senescence. Conference proceedings. Ardmore, Oklahoma, December 15-18, 1991.

PMID- 1360906
TI  - Intrastriatal dopamine-rich grafts induce a hyperexpression of Fos protein when
      challenged with amphetamine.
AB  - The aim of the present experiment was to characterize the effect of intrastriatal
      grafts of embryonic dopaminergic neurones on the expression of Fos protein in the
      striatum when challenged with amphetamine. Unilateral 6-hydroxydopamine lesions
      of the nigrostriatal pathway were made in adult rats and grafting was performed 3
      weeks later. The numbers of Fos-positive nuclei in the ipsi- and contralateral
      striata were counted on coronal sections following immunohistochemical staining 5
      months after grafting. Administration of d-amphetamine induced an increase in the
      density of Fos-positive nuclei in the intact striatum. This stimulatory effect of
      amphetamine on c-fos expression was blocked by 6-hydroxydopamine hydrobromide
      lesions and was restored in the striata bearing transplants. However, an
      overshoot was observed as the density of Fos-positive cells within the grafted
      striatum was larger than that observed within the intact striatum. This
      hyperexpression of Fos-positive nuclei was correlated with the exaggerated
      compensation of amphetamine-induced rotation in the same animals.

PMID- 1360907
TI  - Gradient expression of Cdx along the rat intestine throughout postnatal
      development.
AB  - Rat genomic DNA was isolated by homology with Cdx1, a murine homeogene
      selectively expressed in intestinal cells of endodermal origin. Southern blot
      analysis indicated that the rat genome contains a single or a small number of
      closely related Cdx gene(s). A major 1.7 kb Cdx mRNA was detected in neonate,
      suckling and adult rats whereas a 6.5 kb mRNA was restricted to sucklings and
      adults. Both transcripts showed decreasing concentration from the colon towards
      the proximal part of the small intestine. No obvious correlation could be
      established with the patterns of expression of transcripts corresponding to
      markers of cell proliferation and cell differentiation during postnatal
      development.

PMID- 1360909
TI  - [Regulation of growth hormone-releasing hormone gene expression and secretion].
AB  - Growth hormone (GH)-releasing hormone (GRH) is a stimulatory hypothalamic
      hypophysiotropic hormone which, along with an inhibitory peptide, somatostatin
      (SRIF), regulates the synthesis and secretion of GH in anterior pituitary
      somatotrophs. Although GHRH genes in several species have been characterized,
      there is only a limited understanding of the neural and hormonal mechanisms
      regulating GRH biosynthesis and secretion. Recent progress in PCR and in situ
      hybridization techniques as well as hGRF-transgenic animal models have provided
      an opportunity to study the regulation of GRH gene expression and secretion as
      well as its metabolism. The difference in 5'-untranslated sequences in both mouse
      and rat GRH cDNAs from hypothalamus and placenta has also suggested tissue
      specific regulation of the GRH gene. GH excess has been shown to result in a
      decrease in hypothalamic GRH mRNA as well as GRH content and secretion while GH
      deficiency caused by hypophysectomy, hypothyroidism or genetic dwarfism causes an
      increase in GRH mRNA levels as tested by Northern blot analysis or in situ
      hybridization. Treatment of animals with GH or SRIF inhibits the increased GRH
      gene expression in the hypothalamic arcuate nucleus. Double immunocytochemistry
      for hypothalamic GRH and SRIF has shown both axo-perikaryal and axo-axonal
      connections between GRH- and SRIF- containing neurons. SRIF binding and GH
      receptor mRNA are demonstrated on a subpopulation of GRH-containing neurons in
      the hypothalamic arcuate nucleus. It is therefore possible to conclude that
      regulation of GRH gene expression, primarily related to inhibitory feedback
      effects of GH and IGFs on hypothalamic GRH gene expression, is mediated at least
      in part by SRIF or GH. The single transcript of the human GRH gene encodes a 108
      amino acid precursor, prepro-hGRH, which is cleaved into the signal peptide and
      the remaining peptide, pro-hGRH. The latter is further processed to yield two
      equipotent forms of the releasing hormone, hGRH(1-44)-NH2, hGRH(1-40)-OH, and a
      carboxyl-terminal peptide (hGCTP) of unknown function. Studies in transgenic mice
      demonstrate the processing of hGRH-prohormone into both mature forms of hGRH and
      hGCTP, and provide evidence that hGRH(1-40)-OH is derived from hGRH(1-44)
      NH2.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1360908
TI  - Gamma-COP, a coat subunit of non-clathrin-coated vesicles with homology to
      Sec21p.
AB  - Constitutive secretory transport in eukaryotes is likely to be mediated by non
      clathrin-coated vesicles, which have been isolated and characterized [(1989) Cell
      58, 329-336; (1991) Nature 349, 215-220]. They contain a set of coat proteins
      (COPs) which are also likely to exist in a preformed cytosolic complex named
      coatomer [(1991) Nature 349, 248-250]. From peptide sequence and cDNA structure
      comparisons evidence is presented that one of the subunits of coatomer, gamma
      COP, is a true constituent of non-clathrin-coated vesicles, and that gamma-COP is
      related to sec 21, a secretory mutant of the yeast Saccharomyces cervisiae.

PMID- 1360910
TI  - Intradomestic mosquito breeding sources and their management.
AB  - Seven mosquito species were found to breed in intradomestic breeding sources. An.
      stephensi and An. subpictus bred in almost all types of containers. Among the
      culicines, Cx. quinquefasciatus and Ae. aegypti were predominant. Larval breeding
      was controlled through source reduction or introduction of larvivorous fish
      Poecilia reticulata. Health education helped in acceptance of the programme by
      the community. Intradomestic breeding positivity was 2-6% and 16-31% in
      experimental and control areas respectively.

PMID- 1360911
TI  - Regulation of growth hormone secretion.
AB  - The secretion of growth hormone (GH) is controlled by a complex regulatory
      system. The primary control is exerted by two neuroendocrine hormones, GH
      releasing hormone and somatostatin, though other hypothalamic neuropeptides
      directly and indirectly participate in this process. The regulation of each of
      these neurohormones is now being clarified at both physiologic and molecular
      levels, as are their respective roles in the generation of pulsatile GH secretion
      and in GH feedback regulation. Considerable information has been amassed
      concerning signal transduction systems mediating the effects of hypothalamic
      hormones on GH secretion. Although multiple second messengers have been
      implicated, the adenylate cyclase-cyclic AMP-protein kinase A system appears to
      exert a predominant role. The developmental regulation of the somatotropes and of
      GH gene expression is also of importance in determining the GH responses to
      releasing and inhibiting hormones. The availability of several rodent strains
      with genetic disorders of growth associated with impaired GH secretion, along
      with the development of transgenic models, has permitted a more detailed analysis
      of the role of cytokines and growth factors on both somatotrope biology and
      hormone secretion. Finally, knowledge gained from studies in animals is
      permitting a better understanding of the mechanisms involved in physiologic GH
      secretion and altered GH secretion associated with specific disease states in
      humans.

PMID- 1360912
TI  - The role of prophylactic oophorectomy in the avoidance of ovarian cancer.
AB  - OBJECTIVE: To determine the role of prophylactic oophorectomy at elective
      hysterectomy in the avoidance of ovarian cancer. METHOD: A survey was performed
      of all members of the Society of Gynecologic Oncologists and all obstetrician
      gynecologists in the State of Connecticut. RESULT: Seventy-nine percent of
      gynecologic oncologists and 72% of obstetrician-gynecologists surveyed reported 0
      1% of women would be saved from ovarian cancer if one ovary was removed at
      elective hysterectomy at age 45 years. If both ovaries were removed, 8.4% and
      32.1% of these physicians respectively responded that 95-100% of women could be
      saved from ovarian cancer. Approximately 50% responded that macroscopic
      appearance and frozen section studies at surgery were helpful in deciding whether
      to remove ovaries at hysterectomy. A literature review suggested that 12% of
      ovarian cancers might be avoided if women undergo prophylactic oophorectomy at
      elective hysterectomy. CONCLUSION: There is a lack of well-designed epidemiologic
      studies evaluating risk factors for ovarian cancer and the role of prophylactic
      oophorectomy at elective hysterectomy.

PMID- 1360913
TI  - Medication during pregnancy: an intercontinental cooperative study. Collaborative
      Group on Drug Use in Pregnancy (C.G.D.U.P.).
AB  - OBJECTIVE: To assess the current situation in pregnancy drug prescription across
      various cultural and health care settings. METHOD: An international study was set
      up to collect by questionnaire survey comparable data. A total of 14,778 women
      giving birth in 148 hospitals from 22 countries were enrolled. RESULT:
      Antenatally, 14% of women received no drugs, while drug takers received an
      average of 2.9 prescriptions. There were marked intercountry variations in
      prescribing habits. The majority of prescriptions referred to iron and vitamins.
      Anti-infectives were the second most widely taken drugs. Anti-inflammatory drugs
      were taken by 17% of women, these in 42% of cases being self-administered. During
      the intrapartum period 79% of the women received an average of 3.3 drugs. Besides
      analgesics/anesthetics (31.8%), the most commonly prescribed drugs were oxytocin
      (17.5%), ergot derivatives (8.4%) and anti-infectives (5.3%). At the time of
      interview 91% of women were planning to breastfeed. Methylergometrin led the list
      of most frequently used drugs (36%) given to breastfeeding women, although the
      use of ergot derivatives in the puerperium showed wide intercountry variations.
      CONCLUSION: The survey has confirmed that at present, some drugs are often more
      widely used in pregnancy than is justified by the knowledge available.

PMID- 1360914
TI  - Maternal mortality in Assiut.
AB  - Twenty-nine maternal deaths were identified among 8656 pregnant women residing in
      Assiut city and three surrounding villages (Upper Egypt). This gives a maternal
      mortality ratio of 368 per 100,000 live births. Of these maternal deaths 83% were
      due to direct obstetric causes (hemorrhage, eclampsia, ruptured uterus and
      sepsis). Logistic regression analysis showed that residence (in villages versus
      Assiut city), parity (nullipara and grandmultipara) and illiteracy were
      significantly associated with increased risk of maternal death.

PMID- 1360915
TI  - The obstetric fistula: factors associated with improved pregnancy outcome after a
      successful repair.
AB  - A retrospective study of 155 pregnant patients with obstetric fistulae was
      conducted to determine the factors associated with improvement in the pregnancy
      outcome. The successful repair of the fistula was associated with a reduced
      abortion rate (4.0%), incidence of premature rupture of the membranes (1.3%)
      perinatal mortality (13.0%) as well as an increase in the mean fetal birthweight
      and reduced incidence of low birth (20.3%). Antenatal supervision of pregnancy
      increased the acceptance rate for elective cesarean section and was associated
      with early referral of cases to hospital during labor. The patients having their
      first pregnancies since the onset of their fistulae delayed longest in labor at
      home (15.6 h) hence had the highest perinatal mortality and rate of recurrence of
      obstetric fistula. Therefore the successful repair of the obstetric fistula
      together with an aggressive drive to improve antenatal supervision especially
      directed at the younger patients will improve acceptance of the policy of
      elective cesarean delivery and therefore the overall pregnancy outcome among
      these patients.

PMID- 1360916
TI  - Racial differences in patients with adenocarcinoma of the endometrium.
AB  - OBJECTIVE: To determine the differences between white and black women with regard
      to the presentation and behavior of adenocarcinoma of the endometrium. METHOD:
      Records of 273 (68%) white patients and 117 (32%) black patients with endometrial
      adenocarcinoma were reviewed in Bloemfontein, South Africa. Survival data was
      calculated according to the direct method where losses in follow-up were regarded
      as tumor deaths. RESULTS: Most patients (82%) were treated by pre-operative
      radium followed by total abdominal hysterectomy and bilateral salpingo
      oophorectomy, with post-operative external irradiation where indicated. Pre
      operatively, fewer black women had reached FIGO stage I, while a larger number
      had advanced to stages II-IV (P = 0.0024). In addition, the tumor differentiation
      was more often poor in the black group (P < 0.0001). Ten-year follow-up was
      achieved in 84% of the white patients and 51% of the black patients and the 10
      year survival figures were 67% for white patients and 28% for blacks (P <
      0.0001). CONCLUSION: Endometrial adenocarcinoma is a more aggressive disease in
      black women than it is in whites.

PMID- 1360917
TI  - Lipid and hormonal profile of Panamanian women during the menstrual cycle.
AB  - Forty-one women of reproductive age were included in the study, to establish the
      variation of serum lipids during the menstrual cycle and simultaneously, to
      determine the physiological fluctuation of FSH, LH, prolactin (PRL), progesterone
      (P4) and estradiol (E2) concentration in serum, during the menstrual cycle. A
      significant decrease of total serum cholesterol (165.29 +/- 3.6 mg/dl) and
      triglycerides (108.99 +/- 9.65) occurred during the luteal phase, as compared
      with the follicular phase (176.16 +/- 3.51, 108.99 +/- 9.65). Changes were not
      observed with HDL-cholesterol during the cycle. On the other hand, FSH showed an
      initial rise (mean 5 IU/l) followed by a surge (10 IU/l) and a progressive fall
      toward the midcycle. In contrast LH secretion showed a steady increase with a
      maximal concentration at surge (32.1 IU/l). PRL mean value was observed, with a
      discrete increase after day 13 of the menstrual cycle, that was more noticeable
      at the end of the cycle. Forty-eight hours after the FSH and LH midcycle surge,
      elevation of progesterone was observed, with maximal concentration occurring on
      day 24 (23 nmol/l) and later on progesterone levels fell rapidly. Thirty-six to
      24 h before the surge of LH and FSH at midcycle was observed the peak serum
      concentration of estradiol (1300 pmol/l) followed by a progressive fall. Changes
      in the concentration of serum lipids during the menstrual cycle are presumably
      due to a direct or indirect effect of physiological fluctuation of sex hormones.

PMID- 1360918
TI  - In vitro fertilization program based on programmed cycles monitored by ultrasound
      only.
AB  - OBJECTIVE: Programmed oocyte retrieval was performed in order to make the in
      vitro fertilization (IVF) program cheaper and work of the IVF team easier.
      METHOD: In a group of 77 patients included in the IVF program, the menstrual
      cycle was modified with estrogen-progesterone contraceptive pills. For this
      reason, it was possible to start the stimulation protocol in all patients on the
      same day. The stimulation protocol was a combination of clomiphene (100 mg) for 5
      days and HMG (150 IU) every other day. Cycles were monitored by ultrasound only.
      RESULT: The implantation rate per embryo transfer was 22.4%. The number of
      embryos per embryo transfer was low (2.6 +/- 1.4) and eliminated the need for
      cryopreservation. Fertilization rate (82%) and embryo transfer rate (87%) were
      high. The take home baby rate was 14.3%. CONCLUSION: Seventy percent of all
      punctures were performed in 3 days in the middle of the week. In our conditions,
      programmed oocyte retrieval is associated with significant economic benefits.

PMID- 1360919
TI  - Vertical transmission of hepatitis C virus infection.

PMID- 1360920
TI  - North Jordan experience with vaginal birth after cesarean section.

PMID- 1360921
TI  - Early sonographic diagnosis of fetal acrania.

PMID- 1360922
TI  - Carcinoma of the breast. ACOG Technical Bulletin Number 158--August 1991.
AB  - In the United States, breast cancer is the leading cause of cancer death in women
      aged 35-54. The cause is not known, and 80% of women with breast cancer do not
      have any of the known risk factors. Mass screening with mammography is the only
      effective method of reducing breast cancer mortality. Early detection discovers
      smaller lesions for which breast-sparing treatments may be appropriate. The
      obstetrician-gynecologist should recognize the breast examination is an integral
      part of the gynecologic examination.

PMID- 1360924
TI  - Credentialing guidelines for operative laparoscopy. ACOG Committee Opinion:
      Committee on Gynecologic Practice. Number 106--April 1992.

PMID- 1360923
TI  - Postpartum tubal sterilization. ACOG Committee Opinion: Committee on Obstetrics:
      Maternal and Fetal Sterilization. Number 105--March 1992.

PMID- 1360925
TI  - Credentialing guidelines for operative hysteroscopy. ACOG Committee Opinion:
      Committee on Gynecologic Practice. Number 107--April 1992.

PMID- 1360926
TI  - Thyroid stimulating immunoglobulins, like thyrotropin activate both the cyclic
      AMP and the PIP2 cascades in CHO cells expressing the TSH receptor.
AB  - In human thyrocytes and in a permanent CHO cell line expressing the human thyroid
      stimulating hormone (TSH) receptor cDNA (JP09 cells), TSH activates both the
      cyclic AMP and the phosphatidylinositol 4,5-bisphosphate (PIP2) cascade, although
      the latter effect requires higher TSH concentrations. Thyroid stimulating
      autoantibodies (TSAb) activate also the human thyroid leading to the
      hyperthyroidism of Graves' disease. They bind to the TSH receptor and mimic the
      TSH stimulation of the gland by increasing intracellular cyclic AMP, but they do
      not enhance PIP2 hydrolysis in human thyroid slices. We show in this study that
      TSAb are able to activate the PIP2 cascade in JP09 cells, a cell line expressing
      high levels of TSH receptor. This suggests that the mechanism of action of TSAb
      on the TSH receptor is qualitatively similar to that of TSH.

PMID- 1360927
TI  - Somatostatin binding and modulation of adenylate cyclase in ovine retina
      membranes.
AB  - Somatostatin (SS) receptors in membranes from ovine retinas were examined using
      125I-Tyr11-SS as a ligand. Receptor binding was rapid, specific, saturable,
      reversible and dependent on temperature and membrane concentration. Conditions of
      apparent equilibrium were obtained at 25 degrees C after a 45 min incubation in
      the presence of about 0.25 mg membrane protein/ml. Native SS competitively
      inhibited the binding of 125I-Tyr11-SS in the range of 0.01-10 nM, and half
      maximal inhibition was observed at 0.2 nM SS. Scatchard analysis of these data
      suggested the existence of a single population of SS receptors with a
      dissociation constant of 0.23 +/- 0.03 nM and a maximum binding capacity of 84 +/
      6 fmol/mg protein. The binding of 125I-Tyr11-SS was inhibited by various
      synthetic SS analogs in a dose-dependent manner whereas peptides unrelated to SS
      did not show practically any effect even at concentrations as high as 10(-6) M.
      SS receptor occupancy appears to be coupled to inhibition of adenylate cyclase
      activity by a guanine nucleotide-binding regulatory protein, as suggested by the
      facts that: (a) SS noncompetitively inhibited the stimulatory effect of
      vasoactive intestinal peptide (VIP) (3 x 10(-7) M) on membrane adenylate cyclase
      activity but it did not alter basal enzyme activity; and (b) the addition of
      guanosine 5'-triphosphate (GTP) (10(-5) M) decreased the specific binding of 125I
      Tyr11-SS to 26.6% of the control value due to a decrease in SS receptor affinity.
      The present results support the hypothesis that SS may contribute to the
      physiological regulation of the functions of the retina.

PMID- 1360929
TI  - Toxicity assessment of mercury vapor from dental amalgams.

PMID- 1360928
TI  - Growth hormone and prolactin stimulate androgen receptor, insulin-like growth
      factor-I (IGF-I) and IGF-I receptor levels in the prostate of immature rats.
AB  - In this study we investigated the involvement of several different pituitary
      hormones on rat prostate development. 22-day-old Wistar rats, hypophysectomized
      (hypox) at 19 days of age were supplemented with highly purified human prolactin
      (hPRL), human luteinizing hormone (hLH), porcine follicle-stimulating hormone
      (pFSH), and bovine growth hormone (bGH) or with saline. Quantitative analysis of
      RNAs shows that treatment with either PRL or GH increases significantly steady
      state mRNAs levels of the following genes in the prostate: androgen receptor (AR)
      (respectively 3.5- and 4.8-fold above hypox controls), IGF-I (5- and 2.7-fold),
      and IGF-I receptor (2.9- and 2.3-fold). LH and FSH, by contrast, have negative
      effects on these parameters. To test whether the enhancing effect of PRL and GH
      on AR-mRNA abundance was followed by increased content in the protein itself,
      binding assays were performed with the androgen agonist [3H]R1881 (131 and 153
      fmol/mg protein while hypox controls contained 110 fmol/mg protein). In addition
      to the well-documented presence of prolactin receptors in prostatic tissues, we
      have further demonstrated, by means of nuclease S1 protection assays plus dot-
      and Northern-blot analyses, that a GH receptor mRNA is produced in the immature
      rat prostate. Moreover, we observed not only strong lactogenic but also purely
      somatogenic binding to be occurring in the immature prostates. Finally, we have
      studied IGF-I mRNA content in separated epithelial/stromal cell fractions and
      have concluded that IGF-I expression is principally located in the prostatic
      stroma. Taken together, these results suggest that PRL and GH are involved in
      regulating AR synthesis, at least partially by direct action on the organ. In
      this context IGF-I appears as a paracrine factor playing a role in
      epithelium/stroma interactions during prostatic development.

PMID- 1360930
TI  - Identification and characterization of GroEL and DnaK homologues in Thiobacillus
      ferrooxidans.
AB  - The major heat shock proteins from Thiobacillus ferrooxidans were identified as
      DnaK and GroEL equivalents by Western blotting and analysis of the N-terminal
      amino acid sequence of spots isolated from dried 2-D polyacrylamide
      electrophoresis gels. The T. ferrooxidans chaperonins showed 70% and 80% identity
      with the Escherichia coli GroEL and DnaK, respectively. By using electrophoresis
      with a transverse pore gradient of cross-linked polyacrylamide and nondenaturing
      conditions followed by Western blotting, we found that the GroEL proteins from
      both bacteria formed a 14-mer, whereas E. coli DnaK protein existed partially as
      a dimer and the T. ferrooxidans DnaK-equivalent showed only a monomeric nature
      under our experimental conditions.

PMID- 1360931
TI  - Generation of a restriction fragment length polymorphism linkage map for
      Toxoplasma gondii.
AB  - We have constructed a genetic linkage map for the parasitic protozoan, Toxoplasma
      gondii, using randomly selected low copy number DNA markers that define
      restriction fragment length polymorphisms (RFLPs). The inheritance patterns of 64
      RFLP markers and two phenotypic markers were analyzed among 19 recombinant
      haploid progeny selected from two parallel genetic crosses between PLK and CEP
      strains. In these first successful interstrain crosses, these RFLP markers
      segregated into 11 distinct genetic linkage groups that showed close correlation
      with physical linkage groups previously defined by molecular karyotype. Separate
      linkage maps, constructed for each of the 11 chromosomes, indicated recombination
      frequencies range from approximately 100 to 300 kb per centimorgan. Preliminary
      linkage assignments were made for the loci regulating sinefungin resistance (snf
      1) on chromosome IX and adenine arabinoside (ara-1) on chromosome V by linkage to
      RFLP markers. Despite random segregation of separate chromosomes, the majority of
      chromosomes failed to demonstrate internal recombination events and in 3/19
      recombinant progeny no intramolecular recombination events were detected. The
      relatively low rate of intrachromosomal recombination predicts that tight linkage
      for unknown genes can be established with a relatively small set of markers. This
      genetic linkage map should prove useful in mapping genes that regulate drug
      resistance and other biological phenotypes in this important opportunistic
      pathogen.

PMID- 1360932
TI  - Reduced levels of DNA polymorphism and fixed between-population differences in
      the centromeric region of Drosophila ananassae.
AB  - We have estimated DNA sequence variation within and between two populations of
      Drosophila ananassae, using six-cutter restriction site variation at vermilion
      (v) and furrowed (fw). These two gene regions are located close to the centromere
      on the left and right X chromosome arms, respectively. In the fw region, no DNA
      polymorphism was detected within each population. In the v region, average
      heterozygosity per nucleotide was very low in both populations (pi = 0.0005 in
      the Burma population, and 0.0009 in the India population). These estimates are
      significantly lower than those from loci in more distal gene regions. The
      distribution of DNA polymorphisms between both populations was also striking. At
      fw, three fixed differences between the Burma and India populations were detected
      (two restriction site differences and one insertion/deletion of approximately 2
      kb). At v, each DNA polymorphism in high frequency in the total sample was nearly
      fixed in one or the other population, although none of them reached complete
      fixation. The observed pattern of reduced variation within populations and fixed
      differences between populations appears to correlate with recombination rate. We
      conclude that recent hitchhiking associated with directional selection is the
      best explanation for this pattern. The data indicate that different selective
      sweeps have occurred in the two populations. The possible role of genetic
      hitchhiking in rapid population differentiation in gene regions of restricted
      recombination is discussed.

PMID- 1360933
TI  - Comparative genome mapping of Sorghum and maize.
AB  - Linkage relationships were determined among 85 maize low copy number nuclear DNA
      probes and seven isozyme loci in an F2 population derived from a cross of Sorghum
      bicolor ssp. bicolor x S. bicolor ssp. arundinaceum. Thirteen linkage groups were
      defined, three more than the 10 chromosomes of sorghum. Use of maize DNA probes
      to produce the sorghum linkage map allowed us to make several inferences
      concerning processes involved in the evolutionary divergence of the maize and
      sorghum genomes. The results show that many linkage groups are conserved between
      these two genomes and that the amount of recombination in these conserved linkage
      groups is roughly equivalent in maize and sorghum. Estimates of the proportions
      of duplicated loci suggest that a larger proportion of the loci are duplicated in
      the maize genome than in the sorghum genome. This result concurs with a prior
      estimate that the nuclear DNA content of maize is three to four times greater
      than that of sorghum. The pattern of conserved linkages between maize and sorghum
      is such that most sorghum linkage groups are composed of loci that map to two
      maize chromosomes. This pattern is consistent with the hypothesized ancient
      polyploid origin of maize and sorghum. There are nine cases in which locus order
      within shared linkage groups is inverted in sorghum relative to maize. These may
      have arisen from either inversions or intrachromosomal translocations. We found
      no evidence for large interchromosomal translocations. Overall, the data suggest
      that the primary processes involved in divergence of the maize and sorghum
      genomes were duplications (either by polyploidy or segmental duplication) and
      inversions or intrachromosomal translocations.

PMID- 1360935
TI  - The 3rd Symposium by the 7 Winners of the Grants from Sandoz Foundation for
      Gerontological Research. Yokohama, Japan, November 5, 1991.

PMID- 1360936
TI  - A retrospective comparative study of reconstructive methods following
      pancreaticoduodenectomy--pancreaticojejunostomy vs. pancreaticogastrostomy.
AB  - Reconstructive methods following pancreaticoduodenectomy in our department are
      discussed and evaluated in this study. Between January 1980 and November 1990
      fifty-two consecutive patients underwent pancreaticoduodenectomy because of
      pancreas head disease. Thirty-one patients underwent pancreaticojejunostomy and
      twenty-one had pancreaticogastrostomy as reconstructive procedures. Mortality
      rate was 6% in pancreaticojejunstomy versus zero in pancreaticogastrostomy. Six
      patients had leakage from the pancreaticojejunostomy, but only one patient had
      necrosis of the gastric stump and leakage from the pancreaticogastrostomy. This
      case had previous distal gastrectomy done for gastric ulcer. The residual stomach
      might not have been large enough, and the blood supply of the gastric stump might
      not have been adequate for pancreaticogastrostomy. Except for this case, none was
      observed with leakage from the pancreatic anastomosis in the
      pancreaticogastrostomy group. No statistical significance in operating time or
      blood loss was observed between the two methods. The pancreaticogastrostomy cases
      without complications had significantly less loss of body weight than those with
      pancreaticojejunostomy at the date of discharge (p < 0.05). It is concluded that
      pancreaticogastrostomy is the safer reconstructive method following
      pancreaticoduodenectomy, although it may not be indicated in patients with prior
      gastrectomy.

PMID- 1360937
TI  - Conservative treatment of acute pancreatitis: the use of somatostatin.
AB  - The aim of the medical treatment of acute pancreatitis is to rest the gland and
      to reduce complication and mortality rates. The effect of various treatment
      modalities on the course and outcome of acute pancreatitis have been
      disappointing. This review critically considers the results of reported
      therapeutic trials and our own unpublished data of somatostatin and its long
      acting synthetic analogue, octreotide, in acute pancreatitis. It is concluded
      that somatostatin is a promising drug. It reduces pancreatic enzyme secretion,
      the clinical need for analgesic drug administration, and the local complication
      rate, and shortens hospitalization. However, its effect on mortality rates is
      questionable. It is suggested that large-scale, carefully designed studies of
      somatostatin are needed to evaluate the beneficial effect of this drug on the
      course and outcome of acute pancreatitis. Since most of the trials included
      pancreatitis of various etiologies, it is also suggested that cases of acute
      biliary pancreatitis should be excluded or evaluated separately, as these
      patients are best treated by endoscopic sphincterotomy.

PMID- 1360934
TI  - High density molecular linkage maps of the tomato and potato genomes.
AB  - High density molecular linkage maps, comprised of more than 1000 markers with an
      average spacing between markers of approximately 1.2 cM (ca. 900 kb), have been
      constructed for the tomato and potato genomes. As the two maps are based on a
      common set of probes, it was possible to determine, with a high degree of
      precision, the breakpoints corresponding to 5 chromosomal inversions that
      differentiate the tomato and potato genomes. All of the inversions appear to have
      resulted from single breakpoints at or near the centromeres of the affected
      chromosomes, the result being the inversion of entire chromosome arms. While the
      crossing over rate among chromosomes appears to be uniformly distributed with
      respect to chromosome size, there is tremendous heterogeneity of crossing over
      within chromosomes. Regions of the map corresponding to centromeres and
      centromeric heterochromatin, and in some instances telomeres, experience up to 10
      fold less recombination than other areas of the genome. Overall, 28% of the
      mapped loci reside in areas of putatively suppressed recombination. This includes
      loci corresponding to both random, single copy genomic clones and transcribed
      genes (detected with cDNA probes). The extreme heterogeneity of crossing over
      within chromosomes has both practical and evolutionary implications. Currently
      tomato and potato are among the most thoroughly mapped eukaryotic species and the
      availability of high density molecular linkage maps should facilitate chromosome
      walking, quantitative trait mapping, marker-assisted breeding and evolutionary
      studies in these two important and well studied crop species.

PMID- 1360938
TI  - Psychotic depression: advances in conceptualization and treatment.
AB  - Psychotic depression is a unique subtype of depressive illness in which mood
      disturbance is accompanied by delusions, hallucinations, or both. Once considered
      relatively uncommon, it is frequently encountered in clinical practice,
      particularly in treatment-resistant depressed patients. Psychotically depressed
      patients respond poorly to antidepressants, but remission is likely with
      neuroleptic-antidepressant combinations or electroconvulsive therapy. Psychotic
      depression may be unipolar or bipolar with early or late onset and may be more
      likely to occur in patients with a history of childhood psychic trauma. Much is
      known about the course and treatment response of obvious presentations of
      psychotic depression, but more must be learned about depressed patients who have
      intermittent, subtle, or mild psychotic symptoms and about the ways in which the
      capacity to become psychotic interacts with the capacity to become depressed to
      produce a syndrome greater than the sum of its parts.

PMID- 1360939
TI  - Differences between chronic schizophrenic patients in the hospital and in the
      community.
AB  - Clinical differences between stable, chronic schizophrenic patients with long
      stays in the hospital and schizophrenic patients living in the community were
      investigated. Patients were matched for age, gender, and diagnosis. Hospitalized
      patients had more severe thought disorder and negative symptoms, and those in the
      community had a significantly higher incidence of depression and anxiety. The
      community-based patients were also receiving higher doses of neuroleptic drugs
      and had a higher incidence and severity of extra-pyramidal side effects. Results
      suggest that living in the community, despite its obvious benefits, may have its
      price in terms of the distressing effects of affective symptoms and neuroleptic
      side effects.

PMID- 1360940
TI  - Linkage analysis of the D1 dopamine receptor gene and manic depression in six
      families.
AB  - Disturbances in dopaminergic activity may play an important role in the
      pathogenesis of manic depression. The effects of dopamine are mediated by at
      least five G protein coupled receptors, D1, D2, D3, D4 and D5. Recently, three
      separate research groups have cloned and characterized the D1 dopamine receptor,
      which localizes to 5q35.1. We undertook a linkage analysis between the D1
      receptor polymorphisms and manic depression in six families in which segregation
      of the disease was consistent with autosomal dominant inheritance. A highly
      polymorphic flanking DNA marker, CRI-L1200, was also analyzed as the D1 gene
      RFLPs were relatively uninformative in our families. Multipoint analyses of manic
      depression and these DNA markers resulted in lod scores of less than -3.0 at the
      D1 locus, indicating that the D1 dopamine receptor gene does not confer an
      inherited susceptibility to manic-depressive illness in the families studied.

PMID- 1360941
TI  - Leber's hereditary optic neuroretinopathy and the X-chromosomal susceptibility
      factor: no linkage to DXs7.
AB  - Leber's hereditary optic neuroretinopathy (LHON) was the first human disease for
      which mitochondrial inheritance was demonstrated. Analysis of genealogies,
      however, suggests the existence of an interacting X-linked factor, and linkage to
      DXS7 was recently described. We tested this location in four LHON families, with
      DXS7 and two flanking markers, OTC and DXS426. We found recombinations with DXS7
      in two families and with DXS426 in one. The two point lod scores to DXS7 were
      negative with all the allele frequencies for the X-linked factor tested (q = 0.5;
      0.35; 0.05).

PMID- 1360942
TI  - Haemopoietic stem cells during development of mouse embryo.
AB  - Haemopoiesis in mammals takes place in yolk-sac and in mouse it can be detected
      on the 7th day of gestation. Erythropoietin (EPO) responsive cells can be
      detected from 7th day onwards. However, the cells committed to the myeloid
      lineage which can respond to the haemopoietic growth factor (viz. granulocyte
      macrophage colony stimulating factor; GM-CSF) can be demonstrated only on 10th
      day of gestation. At the same time, the 12-day spleen colony forming cells i.e.
      the late colony forming unit spleen (CFU-s) which are multipotent stem cells can
      also be detected. Data suggest that the stem cells seen in the embryo from 7-10
      days of gestation may be a primitive population confined only to the yolk-sac.
      Liver haemopoiesis which begins in the liver of 13-day embryos is due to
      primitive haemopoietic pluripotent stem cells, arising de novo in the embryo and
      not in the yolk-sac, since no primitive pluripotent stem cells capable of
      repopulating lethally irradiated bone-marrow can be detected in the yolk-sac.

PMID- 1360943
TI  - Dopaminergic modulation of footshock induced aggression in paired rats.
AB  - Footshock induced aggression (FIA) was induced in weight matched paired rats and
      three paradigms of aggressive behaviour was recorded, namely, the latency to
      fight (LF), total period of physical contact (TPP) and cumulative aggression
      scores (CAS). Dopamine (DA), administered centrally, and peripherally
      administered L-dopa (with benserazide, a peripheral decarboxylase inhibitor), a
      DA precursor, and the postsynaptic D2 receptor agonists, apomorphine, N-n-propyl
      norapomorphine (PNA), bromocriptine, lisuride and pergolide, induced a dose
      related facilitation of FIA characterized by decrease in LF and increase in TPP
      and CAS. However, the DA presynaptic receptor agonist, BHT-920, induced a
      biphasic effect with inhibition of FIA being induced by a lower dose and
      facilitation of the aggressive behaviour produced by a higher dose. The
      postsynaptic D2 receptor antagonists, haloperidol, spiperone and pimozide,
      induced a dose-related attenuation of FIA, an effect not seen with domperidone, a
      peripheral DA receptor antagonist. The results indicate that central dopaminergic
      postsynaptic D2 receptors have a modulatory facilitative effect on FIA, while the
      presynaptic DA autoreceptors mitigate aggressive behaviour. However, the
      presynaptic DA receptor agonist, BHT-920, appears to lose its receptor
      specificity on dose increment. Long term administration of haloperidol, followed
      by withdrawal, or desipramine, induced per se augmentation of FIA and potentiated
      the aggression-facilitative effects of L-dopa, apomorphine and PNA. Since both
      these treatments are known to induce supersensitivity of central postsynaptic
      dopamine D2 receptors, the effects are likely to be related to augmented function
      of dopamine neurones. The findings, in conjunction with a recent report from this
      laboratory indicating an increase in rat brain DA levels in FIA, support the
      contention that the central DA system has a facilitative effect on FIA.

PMID- 1360945
TI  - Histamine-2 receptor antagonists.

PMID- 1360944
TI  - Central histaminergic involvement during stress in rats.
AB  - Effects of some drugs modulating central histaminergic (HA) transmission were
      evaluated on restraint stress (RS)-induced gastric ulcerogenesis, plasma
      corticosterone and immune responses in rats. RS for (i) 6 hr or (ii) 24 hr at
      room temperature, and (iii) 3 hr at 4 degrees C (CRS) all induced gastric mucosal
      erosions and elevated plasma corticosterone levels, the effects with the latter
      two RS procedures being most consistent. Pretreatment of rats with neuronal HA
      depletor, alpha-FMH (100 mg/kg, ip) attenuated both ulcer severity and
      corticosterone response, during both 24 hr RS and CRS. Similar effects were also
      seen with the mast cell degranulator, C-48/80 (10 micrograms/kg, i.c.v.)
      treatment. Further, the H1-blocker, pheniramine (25 mg/kg, ip) but not the
      centrally acting H2-blocker, zolantidine (5 mg/kg, ip) produced clearcut
      attenuations in both stress markers, during the experimental stressors. In rats
      immunized in SRBC, 24 hr RS (and not CRS) significantly prevented the humoral
      immune responses to the antigen. alpha-FMH, C 48/80 and pheniramine but not
      zolantidine, reversed this response during 24 hr RS. The results indicate a
      central HA ergic involvement in the visceral, endocrinal and immune responses
      during RS and suggest the probable role of both neuronal as well as extraneuronal
      (mast cell) HA and activation of H1-receptors in the mediation of these effects.

PMID- 1360946
TI  - Testosterone secretion in children with undescended testis.
AB  - Testicular testosterone (T) production was examined in thirty boys with
      undescended testes (UT) following the administration of 4500 U gonadotropic
      hormone. Twenty boys had bilateral UT and ten had UT plus hypospadias. As for
      possible causes of reduced Leydig cell activity it was investigated whether the
      testis was (1) hypoplastic; (2) abnormally fused with the epididymis; (3) located
      in the abdomen; (4) or UT was associated with hypospadias. Average T values were
      significantly lower when the testicle was hypoplastic or its fusion with the
      epididymis was imperfect; but remained largely undiminished when the testicle was
      located in the abdomen or when UT was combined with hypospadias. The occurrence
      of both pathologic and physiologic T reactions in each of the four groups
      suggests that the population of UT children is heterogeneous, probably due to
      differences in aetiology and in intrauterine hormonal processes. In the case of
      UT and hypoplasia the time and method of operation (orchidopexy) must be selected
      with utmost care, bearing in mind that an originally small testicle with impaired
      T secretion may become physiologic by the time of puberty.

PMID- 1360947
TI  - [Congress of Angiology: Hemodilution therapy, current state of the art. 21st
      annual meeting of the German Society for Angiology. Augsburg, 5 September 1992].

PMID- 1360948
TI  - Detection of P-glycoprotein on endothelial and endocrine cells of the human
      pancreatic islets by C 494 monoclonal antibody.
AB  - P-glycoprotein, an integral membrane protein acting as an energy-dependent efflux
      pump, has been detected immunocytochemically in the human pancreatic islets using
      C 494 monoclonal antibody. Intense P-glycoprotein immunoreactivity was found in
      both endothelial cells of islet blood capillaries and in endocrine cells. Strong
      expression of P-glycoprotein has been found in the capillary blood vessels at
      blood-tissue barrier sites and in numerous kinds of cells with
      secretory/excretory function. Therefore the present findings suggest that P
      glycoprotein may play a role in controlling the composition of the extracellular
      fluids and the intracellular milieu of endocrine islet cells and possibly in
      regulating their secretory activity.

PMID- 1360949
TI  - Statistical associations between restriction fragment length polymorphisms and
      quantitative traits in beef cattle.
AB  - Data on 41 traits from 677 animals produced in a five-breed diallel were matched
      with genotypes for five marker-loci provided by restriction fragment length
      polymorphisms to detect quantitative effects associated with the markers,
      following three different designs based on inbred lines, half-sib families, and
      on assumptions of the markers being quantitative trait loci (QTL). Three growth
      hormone-TaqI alleles, B, C, and D, in high frequencies in this sample of the
      Brahman breed, were associated with decreases in birth weight, as a maternal
      trait (P < .01), and decreases in shoulder width at birth (P < .05). Among F2
      Angus-Brahman and Brahman-Hereford cows, homozygotes for the B, C, or D alleles
      gave birth to calves 4.0 kg lighter than cows homozygous for the A allele, an
      effect that amounts to the magnitude of the corresponding breed difference in the
      diallel, and represents one phenotypic SD. A putative cytoplasmic effect seems to
      interact (P = .02) with this effect on maternal birth weight. Also, at birth, F2
      calves homozygous for the B, C, or D alleles were .8 cm narrower at the shoulders
      than those homozygous for the A allele, after adjusting for birth weight.
      Significant associations (P < .05) between the parathyroid hormone-MspI marker
      and measures of body size were detected, as well as an effect on weaning weight
      (P = .03) as a maternal trait, whose magnitude (17.5 kg) equals the Brahman vs
      Angus and Hereford breed difference, as quantified in the diallel, and represents
      .8 of a phenotypic SD. No significant associations were found for three other
      marker-loci (prolactin-MspI, osteonectin-EcoRI, and keratin VI-MspI). Restriction
      fragment length polymorphisms have the potential to provide new insights and
      useful applications to animal breeding, but, as in this work, small sample sizes,
      extreme susceptibility to Type I errors, and different types of possible
      confounding obfuscate the conclusions that can be drawn from studies of limited
      scope and less than ideal planning.

PMID- 1360950
TI  - Influence of genetic capacity for lean tissue growth on rate and efficiency of
      tissue accretion in pigs fed ractopamine.
AB  - The influence of genetic capacity for lean tissue (LT) growth on responses of
      pigs to ractopamine, in terms of rate and efficiency of body growth and the
      distribution and accretion rate of body tissues, was determined in this study.
      Two sources of pigs representing low and high LT genotypes were used. Within each
      source, two littermate barrows from each of eight litters were individually
      penned and given ad libitum access to a lysine-supplemented, corn-soybean meal
      diet (17.7% CP, 1.08% lysine) containing 0 or 20 ppm of ractopamine hydrochloride
      from 63 to 104 kg. Carcasses were physically dissected into muscle, fatty tissue,
      skin, and bone. Within each source, four additional pigs were killed for
      determination of initial body composition. Pigs of high LT genotype gained BW and
      muscle faster (P < .01), required less (P < .01) feed per unit of gain, and
      produced carcasses that contained more (P < .01) muscle and bone and less (P <
      .01) fatty tissue. Ractopamine increased (P < .01) weight gain and improved (P <
      .01) feed:gain ratio in both genotypes. Ractopamine enhanced the accretion rate
      and the amount of carcass muscle in both genotypes, but the degree of improvement
      was greater in pigs of the high than in those of the low LT genotype (genotype x
      ractopamine, P < .02). Ractopamine also reduced the accretion rate and amount of
      dissectible fat by a greater magnitude in the high LT genotype (genotype x
      ractopamine, P < .04). Based on these data, ractopamine increases muscle
      accretion to a greater degree in pigs with a high genetic capacity for LT growth
      than in those with a low capacity.

PMID- 1360951
TI  - Conference on Comparative Studies of Takayasu Arteritis Among Asian Countries.
      Tokyo, Japan, May 16-17, 1991.

PMID- 1360952
TI  - Comparative studies between Japanese and Korean patients: comparison of the
      findings of angiography, HLA-Bw52, and clinical manifestations.
AB  - A Japan-Korea cooperative survey on Takayasu arteritis has shown some differences
      in the features between Japanese and Korean patients with this disease. In
      angiographic findings, Japanese patients more frequently had lesions at the
      aortic arch and/or its branches (58% of 75 cases), while, in Korean patients, the
      abdominal aorta is the site of relatively frequent lesions (30% of 112 cases).
      Higher occurrence of HLA-Bw52 was found in Japanese patients in comparison with
      Korean patients (46% vs 15%). The presence of HLA-Bw52, however, might have a
      close association with Takayasu arteritis in Korea as well as in Japan. The
      complications in 126 Japanese and 88 Korean patients were also compared. The
      complications occurring with higher frequency in Japanese patients were aortic
      regurgitation, ischemic heart disease, and visual disturbances, while, in Korean
      patients, the more frequent complications were renovascular hypertension as well
      as hypertension of some other etiology.

PMID- 1360953
TI  - Coronary arterial involvement in aortitis syndrome: assessment by exercise
      thallium scintigraphy.
AB  - It is important in patient management to evaluate coronary arterial involvement
      in aortitis syndrome. Twenty-one cases of aortitis syndrome who experienced chest
      pain were examined using exercise thallium scintigraphy. The patients were
      divided into 4 groups according to the angiographic findings. There were five
      patients with left main coronary arterial involvement (group A), four with left
      or right coronary arterial involvement (group B), nine with aortic regurgitation
      (group C), and three with pulmonary arterial involvement (group D). In groups A
      and B, all patients had positive ECGs and thallium perfusion defects. Group A
      patients showed extensive anterolateral perfusion defects, which were compatible
      with left main coronary arterial involvement. Groups C and D patients, who had
      normal coronary arteries, showed no remarkable perfusion defects although five
      had positive ECG findings. Thus, the sensitivity and specificity of exercise
      scintigraphy for detection of myocardial ischemia were 9/9 and 12/12, while those
      of stress ECG were 9/9 and 7/12 (58%), respectively. it is recommended that
      exercise thallium scintigraphy be used for detecting clinically occult but
      significant coronary arterial involvement in aortitis syndrome with chest pain.

PMID- 1360954
TI  - Pathological studies on Takayasu arteritis.
AB  - Takayasu arteritis is a primary inflammatory disease of elastic arteries such as
      the aorta, its larger branches and the pulmonary artery trunk. According to our
      recent statistical survey of autopsy cases in Japan, the frequency of the disease
      in all autopsy cases was approximately 0.033% and the sex ratio was 1:4.5. The
      most frequent ages of the onset were 20-30 years, those of the death were 40-50
      years. The latter was delayed about 20 years in comparison with a previous
      report. In the recent cases, the vascular lesions widely expanded. Luminal
      dilatation and aneurysm formation also increased in frequency, their ratio being
      approximately 57%. In the autopsy cases, the following active lesions were
      observed: (1) acute exudative inflammation (including suppuration), (2) chronic
      non-specific productive inflammation and (3) various types of granulomatous
      inflammation. These findings suggest that many triggers may play a role in the
      morphogenesis of Takayasu arteritis. The inflammatory lesions are produced in the
      media and adventitia through the vasa vasorum, and terminate in a diffuse or
      nodular fibrosis. New active lesions are often observed near the old fibrotic
      ones. This suggests that Takayasu arteritis may be a progressive disease. Intimal
      thickening of the peripheral branches from the affected arteries is very often
      observed. In consequence, secondary ischemic lesions are formed in various
      organs, especially the heart, brain and kidneys.

PMID- 1360955
TI  - Aortic regurgitation in patients with Takayasu arteritis: assessment by color
      Doppler echocardiography.
AB  - To characterize aortic regurgitation in patients with Takayasu arteritis, we
      studied 48 females with arteritis (mean age 47 +/- 12 years) by means of color
      Doppler echocardiography. Aortic regurgitation was confirmed in 32 out of 48
      patients (67%) by color-flow mapping. Twenty-four patients had mild or no aortic
      regurgitation (group A), 9 had moderate (group B), and 15 had severe (group C)
      aortic regurgitation. We compared the echocardiographic data obtained from
      patients with Takayasu arteritis with those of 14 normal controls and 9 patients
      with severe aortic regurgitation of valvular origins (group V). The aortic root
      diameter (AOD) in group B (23 +/- 4 mm/M2) and group C (22 +/- 3 mm/M2) revealed
      a statistically significant large value as compared with that in group A (18 +/-
      2 mm/M2) and normal controls (17 +/- 3 mm/M2). However, the differences, between
      groups B and C and groups C and V, were not significant. The AOD was not
      obviously dilated in a considerable number of group C patients. Aortic valve
      involvement was seen in several group C patients and moderate concentric left
      ventricular hypertrophy was present in all group C patients. Group C patients
      therefore, have concentric left ventricular hypertrophy but may or may not have
      dilatation of the aortic root which can be detected on echocardiography. We
      conclude that aortic valve involvement may cause aortic regurgitation in some
      patients with Takayasu arteritis and that aortic regurgitation is more common
      than previously believed.

PMID- 1360956
TI  - Left ventricular dysfunction and HLA Bw52 antigen in Takayasu arteritis.
AB  - Heart disease is the main cause of death in patients with Takayasu arteritis. It
      has been reported that this disease is closely related to the presence of HLA
      Bw52 antigen. To assess the correlation between this antigen and left ventricular
      involvement, we studied 40 patients with Takayasu arteritis, 21 with and 19
      without Bw52, using Tl-201 stress myocardial scintigraphy and echocardiography.
      Those with Bw52 had a significantly higher incidence of abnormal
      electrocardiographic findings (67% vs 26%; P < 0.05) and of aortic regurgitation
      (52% vs 11%; P < 0.05). The echocardiographically determined interventricular
      septal wall thickness plus left ventricular posterior wall thickness (25 +/- 8 vs
      17 +/- 3 mm; P < 0.01) and the left ventricular mass (257 +/- 132 vs 142 +/- 51
      g; P < 0.01) were significantly increased in the patients with Bw52.
      Scintigraphically determined perfusion abnormalities were significantly more
      frequent in those with Bw52 (76% vs 32%; P < 0.05). These observations indicate
      that patients with Takayasu arteritis and Bw52 antigen have a more severe left
      ventricular involvement than the patients without that antigen. The left
      ventricular impairment may account for the poor prognosis of Takayasu patients
      with Bw52.

PMID- 1360957
TI  - Pregnancy in Takayasu arteritis from the view of internal medicine.
AB  - To evaluate the influence of pregnancy on the morbid condition of Takayasu
      arteritis, we summarized the clinical data and pregnant courses of 18 patients
      with Takayasu arteritis and a total of 22 deliveries. We followed C-reactive
      protein (CRP) scores in 16 of 18 patients (20 of 22 deliveries) to ascertain the
      inflammatory condition inherent in Takayasu arteritis 1 year prior to, during,
      and 1 year after pregnancy. We also evaluated digital plethysmograms (pulse
      amplitude, pulse wave, crest time) to follow the hemodynamical condition of
      patients before, during, and after pregnancy. CRP scores improved significantly
      during pregnancy and 1 year after delivery. In the digital plethysmograms, pulse
      amplitude and wave also exhibited improvement after delivery, but crest time
      remained unchanged. This indicated that pregnancy is a state favorable to this
      disease. Some factors, such as the sex hormone progesterone, may induce this
      condition, but the details are still unknown. In conclusion, inflammatory
      activity and the hemodynamic state improve with pregnancy in patients with
      Takayasu arteritis. The physiologic aspects which cause this improvement should
      be maintained even after pregnancy.

PMID- 1360958
TI  - Clinical gynecologic features of pregnancy in Takayasu arteritis.
AB  - Takayasu arteritis is a non-specific chronic inflammatory vascular disease of
      unknown etiology. Since the incidence of this disease in the child-bearing years
      is relatively high, the management of pregnancies with this disease is of great
      importance in clinical obstetrics. This study is aimed at discussing the maternal
      management and obstetrical outcome, based on the clinical data obtained from 23
      pregnancies of 15 patients treated in our hospital in the past 12 years. Since
      the disease was in the active state, artificial abortions were conducted in four
      cases in the 1st trimester of pregnancy. Among the remaining 16 cases, 3, who
      exhibited neither hypertension nor other complications, vaginally delivered
      neonates weighing 2,660-3,100 g with Apgar scores of nine after 37 weeks'
      gestation. C-sections were performed for 13 patients who showed sustained
      hypertension or/and developed other vascular disorders. Their gestational periods
      ranged from 34 to 40 weeks and the body weight of the infants varied from 1,425
      to 3,024 g. No adverse influence of pregnancy and delivery on Takayasu arteritis
      was detected in the puerperium of any patients. It is suggested that the state of
      Takayasu arteritis in early pregnancy and the magnitude of blood pressure
      elevation in the late gestational period are the most critical and definitive
      factors in determining the management of pregnancy of a patient with Takayasu
      arteritis. Cooperative managements by the specialists in obstetrics, internal
      medicine, and perinatology are required to provide a satisfactory clinical
      outcome.

PMID- 1360959
TI  - Medical treatment of Takayasu arteritis.
AB  - The guidelines for medical treatment of Takayasu arteritis established in 1987 by
      the Systemic Vascular Disorders Research Committee, Ministry of Health and
      Welfare of Japan are presented. The first part of the guidelines concerns
      treatment with adrenocorticosteroids and the second part concerns other medical
      treatment. A review of the literature referring to steroid therapy and other
      medical treatment of Takayasu arteritis is also included.

PMID- 1360960
TI  - Takayasu arteritis: follow-up studies for 20 years.
AB  - We reviewed retrospectively 126 (5 male, 121 female) patients suffering from
      Takayasu arteritis who had been treated in our clinics from 1971 to 1990. The
      patients' ages ranged from 19 to 80 yrs old (1990) with a mean age of 48.7 +/-
      11.8 years. HLA typing analysis in 98 patients revealed that 45 patients (47%)
      were confirmed as carrying the Bw52 antigen, a high result that is statistically
      significant as compared with that in healthy Japanese. Arteriograms (performed in
      75 patients) revealed that 28 patients (37%) were affected in the aorta and its
      main branches by this disease (type IV by Nasu's classification) and 23 patients
      (31%) were affected only in the main branches (type I). The C-reactive protein
      (CRP) and erythrocyte sedimentation rate (ESR) improved significantly from 2.55
      +/- 0.28(+) and 57.0 +/- 5.69 mm/hr to 0.53 +/- 0.12(+) and 31.2 +/- 3.45 mm/hr,
      respectively after treatment including steroid and antiplatelet therapy (P <
      0.01). Patients with Bw52 exhibited more severe inflammatory conditions than
      those without Bw52. Lung scintillations performed in 81 patients showed pulmonary
      arterial lesions in 50 patients (62%). Echocardiograms revealed aortic
      regurgitation (AR) in 44 patients (35%), with a significant difference noted
      between the Bw52 positive group and the Bw52 negative group [29/40 (73%) versus
      11/47 (23%), respectively, P < 0.001]. Patients with Bw52 were prescribed higher
      doses of steroids (P < 0.05) for longer periods (P < 0.01) than those without
      Bw52.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360961
TI  - Percutaneous transluminal angioplasty in Takayasu arteritis.
AB  - Percutaneous transluminal balloon angioplasty (PTBA) was performed in 87 patients
      for 111 stenotic lesions due to Takayasu arteritis. Of the lesions attempted for
      dilatation, 35 were in the aorta, 64 in renal arteries, 9 in subclavian, and 3 in
      common iliac arteries. The stenosis of aorta could be successfully dilated in 33
      of 35 (94.3%) patients with fall in peak systolic pressure gradient (PSG) from
      77.7 +/- 28.4 mmHg to 26.4 +/- 20.6 mmHg (P < 0.001) and increase in luminal
      diameter from 4.7 +/- 2.4 mm to 10.1 +/- 4.1 mm (P < 0.001). On hemodynamic and
      angiographic restudy in 20 patients at 3-24 months (mean 7.7 +/- 4.1 months)
      further fall in PSG (> or = 15 mmHg) was observed in 7 patients, no significant
      change in 12 patients and restenosis with increase in PSG in one patient which
      could be successfully redilated. Late restudy at 36-60 months (mean 43 +/- 9.4)
      in six patients showed continued relief of stenosis (mean PSG 8.8 +/- 7.8 mmHg).
      Of the 64 stenotic lesions of the renal arteries, 58 (90.6%) could be
      successfully dilated with decrease in stenosis from 89.1 +/- 10.1% to 29.9 +/-
      14.9% (P < 0.001). Follow-up intra-arterial digital subtraction angiography in 25
      patients at a mean follow-up period of 13.1 months (range 3-29 months) showed
      restenosis in 5/36 (13.9%) lesions which could be successfully redilated.
      Angioplasty was also successful in dilating 8/9 (88.9%) subclavian and all 3
      common iliac artery stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360962
TI  - Surgical treatment of Takayasu arteritis.
AB  - The role of surgical therapy for Takayasu arteritis remains controversial. From
      1973-1991, 23 patients with Takayasu arteritis have been treated at the
      University of Southern California. Twelve patients have required 17 arterial
      reconstructions for symptomatic complications of arterial disease refractory to
      medical therapy. Indications for operation have included renovascular
      hypertension (7), extremity ischemia (5), cerebrovascular insufficiency (2),
      dilated ascended aorta with aortic insufficiency (1), thoracic aortic aneurysm
      (1), and abdominal aortic aneurysm (1). Long-term clinical follow-up has
      demonstrated uniform symptomatic improvement. Fifteen of seventeen arterial
      reconstructions are still patent. Surgical treatment of symptomatic Takayasu
      arteritis is highly effective. Excellent long-term graft patency can be expected
      following arterial reconstruction.

PMID- 1360963
TI  - Surgical treatment of Takayasu arteritis.
AB  - From 1959 to 1991, 93 patients underwent vascular reconstruction for Takayasu
      arteritis at our institution. The details of the cases were as follows: 16 were
      of type I (brachiocephalic ischemia), 48 type II (hypertension), 13 type III
      (extensive lesions with cerebral ischemia and hypertension), and 16 type IV
      (aneurysms). Carotid reconstruction, repair of atypical aortic coarctation,
      renovascular reconstruction, and aneurysm repair were performed independently or
      in combination. Nine operative deaths occurred, 8 cases of which were operated
      before 1970. The most serious of the delayed complications was suture line
      aneurysm formation, which was encountered in ten cases. The aneurysms were often
      found long after the operation, some of them developing even after more than 20
      years. Takayasu arteritis is characterized by extensive inflammation and
      destruction of the medial elastic fibers and long term postoperative observation
      is mandatory to improve the late survival rate.

PMID- 1360964
TI  - Surgical treatment of cardiac involvement in Takayasu arteritis.
AB  - Cardiac involvement is a serious disorder in Takayasu arteritis. Surgical
      treatment of aortic root and coronary artery lesions due to Takayasu arteritis
      has many potential difficulties due to its inflammatory nature. We operated on 15
      patients with cardiac involvement stemming from Takayasu arteritis. These
      patients are classified into 3 groups depending on the clinical diagnosis and
      surgical procedures employed: coronary artery involvement alone--coronary artery
      bypass grafting (CABG), three patients (group A), aortic regurgitation with
      intact coronary artery--Aortic valve replacement or modified Bentall's operation,
      eight patients (group B), and aortic regurgitation with coronary artery
      involvement g aortic valve replacement or modified Bentall's operation with CABG,
      (4 patients) (group C). CABG was performed using saphenous vein graft. For aortic
      valve replacement or replacement of both the aortic valve and ascending aorta, a
      prosthetic valve or composite graft with Teflon felt flange was fabricated during
      surgery and treated with fibrin glue before insertion. A double fixation method
      with reinforcement by a Teflon felt strip was employed for proximal anastomosis
      of the flanged prosthesis. A button-shaped coronary ostium was directly
      anastomosed to the composite graft. There was no operative or hospital mortality.
      One patient died of brain abscess at 6 months after surgery and another patient
      with CABG required a second operation due to graft failure. Steroid therapy is
      recommended in cases diagnosed as being in an active stage until the inflammatory
      signs disappear.

PMID- 1360965
TI  - Pathological features of the pulmonary artery in Takayasu arteritis.
AB  - Little attention has been paid to the pathological features of the pulmonary
      artery in Takayasu arteritis. Autopsy specimens of 6 cases of this disease were
      studied. Lesions were found in the aortic arch and its brachiocephalic branches
      in all cases and in both the aortic arch and thoracoabdominal aorta in 5 cases.
      The pathohistologic characters of the pulmonary artery were very similar to those
      of the systemic artery. Stenosis-recanalization, so-called blood vessels-in-blood
      vessels, of the pulmonary elastic arteries were found in four cases. These
      lesions were not observed in the systemic arteries, and most of the newly formed
      channels in them seemed to be branches of bronchial arteries. Luminal obstruction
      of pulmonary muscular arteries was observed in 4 cases, cellular arteritis of
      muscular arteries in 2 cases, and angiomatoid dilatation of small blood vessels
      in 2 cases. Thus in this study we found peculiar stenosis-recanalization lesions
      of the pulmonary elastic arteries, and also showed that the pulmonary elastic and
      muscular arteries are frequently involved in Takayasu arteritis. These findings
      suggest that pulmonary hypertension could influence morbidity and long-term
      mortality in this disease.

PMID- 1360966
TI  - Coronary artery lesions in Takayasu arteritis: pathological considerations.
AB  - This communication reviews the clinical and pathological features of coronary
      artery lesions in Takayasu arteritis. The incidence of coronary artery
      involvement has been reported to be 9% to 10%, and is observed mainly in autopsy
      cases because coronary artery disease is usually not evident until the occurrence
      of angina pectoris or myocardial infarction, or after the onset of congestive
      heart failure. On the basis of pathological features, the following three types
      of coronary artery lesions can be distinguished: type 1, stenosis or occlusion of
      the coronary ostia and the proximal segments of the coronary arteries; type 2,
      diffuse or focal coronary arteritis, which may extend diffusely to all epicardial
      branches or may involve focal segments, so-called skip lesions; and type 3,
      coronary aneurysm. Most of the coronary artery lesions in Takayasu arteritis are
      of type 1. Narrowing of the coronary arteries is mainly due to the extension of
      the inflammatory processes of proliferation of the intima and contraction of the
      fibrotic media and adventitia from the ascending aorta. In some cases, coronary
      stenosis may be caused by coronary arteritis as skip lesions in Takayasu
      arteritis, but even in these cases the lesions have been reported to affect
      mainly the proximal segments of the coronary arteries. Diffuse lesions of the
      coronary artery and coronary artery aneurysm seem to be very rare in Takayasu
      arteritis. Other causes of coronary ostial stenosis, coronary arteritis and
      coronary artery aneurysm are also discussed.

PMID- 1360967
TI  - Introductory remarks for this special issue on Takayasu arteritis.

PMID- 1360968
TI  - Takayasu arteritis in China: a report of 530 cases.
AB  - A total of 530 patients with Takayasu arteritis were studied. Among 346 patients
      who were diagnosed by aortography, the female to male ratio was 2.9 to 1, and the
      age of onset ranged from 5 to 45 years. Three hundred and eighteen (60%) patients
      with secondary hypertension, including renovascular hypertension in 281, and 197
      (37.2%) with pulseless extremities were found in the series. All the patients
      were treated with medical or surgical procedures. Surgical treatment is preferred
      if clinical status of the patient permits. The patients were followed for 1-29
      years (average 7.8 years). There were 55 deaths (10.4%) in this series. Cerebral
      hemorrhage was found as a common cause of death. Five-year and ten-year survival
      rates were 93.1% and 91.1%, respectively.

PMID- 1360970
TI  - Takayasu arteritis in Israel.

PMID- 1360969
TI  - Takayasu arteritis in India.
AB  - Takayasu arteritis is the commonest cause of renovascular hypertension in India.
      The clinical and radiological features, complications and course of 83 patients
      (51 females, 32 males) seen during the period from 1972-1990 are described in
      this study. The age of the patients ranged from 5 to 53 years with the mean +/-
      SD of 26.9 +/- 9.7. Hypertension (n = 50) and the related symptom of headache (n
      = 40), dyspnea (n = 24), and giddiness (n = 20) were common at presentation.
      Twelve patients were in congestive cardiac failure. The symptoms of activity with
      fever and arthralgia were present in only 16% contrary to reports from Japan and
      Mexico. Abnormal arterial pulses and bruit over abdominal (37%) or extra
      abdominal great arteries (25%) were useful clinical clues to suspect Takayasu
      arteritis. Rapid sequence intravenous urography was a sensitive screening
      procedure and predicted correctly the presence of renovascular disease in 80% of
      the patients. The diagnosis was confirmed on aortography in 72. In the rest, the
      clinical features and autopsy findings confirmed the same. The four patterns of
      the disease based on the anatomical extent of involvement were recognised. These
      were: type I (n = 8) with involvement of aortic arch and its branches, type II (n
      = 25) descending thoracic and abdominal aorta type III (n = 46) combination of I
      and II and type IV (n = 4) pulmonary artery in addition to any of the
      above.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360971
TI  - Takayasu arteritis in Japan.
AB  - Takayasu arteritis is a disease on which many investigations have been conducted
      to determine its causes, clinical features and treatment, since 1908 when it was
      reported by Dr. Takayasu. The first nationwide epidemiological survey on Takayasu
      arteritis was conducted over 3 years from 1973 through 1975 by a research group
      on "aortitis syndrome", a disease specified by the Ministry of Health and
      Welfare. Another nationwide survey on this disease over a period of 3 years was
      carried out from 1982 through 1984 by a research group focusing on "systemic
      vascular lesion", another disease specified by the Ministry of Health and
      Welfare. The present study reports on the combined results of these two
      nationwide epidemiological surveys.

PMID- 1360973
TI  - An overview on Takayasu arteritis.
AB  - Takayasu arteritis is a non-specific inflammatory disease of unknown etiology. It
      was first recognized as having a peculiar wreath-like arteriovenous anastomosis
      around the papillae of the retina by a Japanese ophthalmologist, Dr. M. Takayasu
      in 1908. A Japanese research committee reported more than 5,000 cases. For a
      supplement issue on Takayasu arteritis, this brief overview article has been
      written as an introduction to the disease.

PMID- 1360972
TI  - Takayasu arteritis in Korea: clinical and angiographic features.
AB  - Clinical and angiographic features of Takayasu arteritis were investigated in 129
      Korean patients. This disease affects females more frequently than males, in a
      ratio of 6.6 to 1. Of the total number of patients, 51 were in the third decade,
      27 in the fourth decade, and 23 in the second decade. Common clinical symptoms
      were headache (60%), exertional dyspnea (42%), dizziness (36%), and malaise or
      weakness (34%). Takayasu arteritis affected the abdominal aorta (46%) and
      descending thoracic aorta (37%) more frequently than the ascending aorta (1%) and
      aortic arch (2%) According to Ueno's classification based on aortographic
      findings, the 129 patients were divided into type I (37), type II (25), and type
      III (67). Among the 48 patients who had coronary angiography, 11 (23%) showed
      coronary arterial involvement. Because the clinical features are determined by
      the extent and severity of the specific artery involved in the occlusive phase of
      the disease, total aortography including coronary angiography is very important
      in the initial evaluation of Takayasu arteritis.

PMID- 1360974
TI  - Takayasu arteritis in Thailand.
AB  - Takayasu arteritis is a disease of world-wide distribution. Geographic difference
      in sex incidence, anatomical distribution, and the type of lesion is observed.
      Hypertension is very common in the present series, as well as in combination with
      absent or deficit of peripheral pulses. These symptoms correlate well with
      arteriographic findings of brachiocephalic and renal artery obstructive lesion.
      While aneurysm and stenotic lesions have a predilection in the abdominal aorta,
      stenotic lesion of the thoracic aorta occurs more commonly than aneurysm.
      However, aneurysm of the aorta as well as of the brachiocephalic arteries is seen
      more frequently than in the reports, of others. The presence of "funnel-shape"
      resulting from renal artery obstructive lesion and dilatation or aneurysm of
      contiguous aorta was characteristic of Takayasu arteritis in our series. The
      material presented in this report reflects not only geographic variation but also
      the severe form of this disease. Total aortography, coronary arteriography and
      pulmonary arteriography, are of value not only for the diagnosis of Takayasu
      arteritis but also for demonstration of anatomical distribution, severity and
      type of lesion.

PMID- 1360975
TI  - Hereditary factors of Takayasu arteritis.
AB  - Takayasu arteritis is a chronic vasculitis characterized by a clinical pulseless
      condition and is predominant in young female patients. Its loci is found mainly
      in Asian countries, and its etiology is still unknown. Our experiences of cases
      of twin sisters with Takayasu arteritis led us to suppose that hereditary factors
      participate in the pathophysiology of this disease. Population and family
      incidence studies employing HLA analysis in Japan have focused on an complotype
      Aw24-DW52-C4A2-C4BQ0-Dw12 which was in disequilibrium with Takayasu arteritis.
      Clinical features and clinical courses were found to be intimately related to
      this complotype. Recent studies on HLA typing in other countries have also
      suggested the important roles of hereditary factors in this morbid condition and
      international collaborative studies on these hereditary factors are now under
      way.

PMID- 1360976
TI  - HLA-linked susceptibility and resistance to Takayasu arteritis.
AB  - To investigate genetic factors involved in the pathogenesis of Takayasu
      arteritis, patients in the Japanese population were examined for HLA-A, -B, and 
      C alleles by serological typing and for HLA-DR, DQ, and DP alleles by DNA typing
      using polymerase chain reaction (PCR)/sequence-specific oligonucleotide probe
      (SSOP) analysis. The frequencies of HLA-Bw52, DRB1*1502, DRB5*0102, DQA1*0103,
      DQB1*0601, and DPB1*0901 alleles were significantly increased and the frequencies
      of HLA-Bw54, DRB1*0405, DRB4*0101, DQA1*0301, and DQB1*0401 alleles were
      significantly decreased. Strong linkage disequilibria among the increased alleles
      and among the decreased alleles were evident in the Japanese population.
      Therefore, the haplotype of HLA-B252-DRB1*1502-DRB5*0102-DQA1*0103-DQB1++ +*0601
      DPA1*02-DPB1*0901 may confer susceptibility to Takayasu arteritis while another
      haplotype of HLA-Bw54-DRB1*0405-DRB4*0101-DQA1*0301-DQB1++ +*0401 may confer
      resistance to the disease. These observations clearly indicate that HLA-linked
      gene(s) are involved in the development of Takayasu arteritis.

PMID- 1360977
TI  - HLA typing of Takayasu arteritis in Korea.
AB  - Takayasu arteritis occurs with a strong predilection for women and particular
      geographic areas, and as related to the etiology of the disease, association of
      HLA antigens has been suggested. In the present study, the authors investigated
      the association of Takayasu arteritis with class I and class II HLA antigens in
      59 Korean patients with this disease. Increased frequencies of HLA-Bw52 (chi 2
      6.213, P < 0.02), Cw6 (chi 2 4.132, P < 0.05), DR7 (chi 2 4.506, P < 0.04), and
      DQw2 (chi 2 7.327, P < 0.01) were observed in the patient group as compared to
      the control group of healthy Koreans. In the Korean population, 2 risk factors in
      the HLA system for developing this disease appear to be (1) Bw52 and (2) DR7 and
      a probable haplotype of Cw6, B13, DR7, DQw2. Previous studies of the Japanese
      population revealed association of Bw52 and class II HLA antigens (DR2, Dw12),
      which are in linkage disequilibrium with Bw52. It is of interest that in the
      Korean population, class II antigens (DR7, DQw2), which are not linked to BW52,
      are associated with the disease. This finding suggests that the disease
      susceptibility gene of Takayasu arteritis is located between the HLA-B locus and
      HLA-DR, DQ loci.

PMID- 1360978
TI  - Immunopathogenesis of Takayasu arteritis.
AB  - Takayasu arteritis is a common cause of renovascular hypertension in India.
      Sensitization to infective agents, particularly mycobacterium tuberculosis or
      autoimmune disturbances have been incriminated in its pathogenesis. Twenty
      patients of Takayasu arteritis along with groups of normal individuals, patients
      of essential hypertension, autoimmune disorders, tuberculosis, and healthy
      tuberculin reactors were studied. Besides detailed immunological profiles
      including LE cell phenomenon, serum complement C3 levels, antibodies to single
      (SS) and double stranded (DS) DNA, rheumatoid factor, lymphocyte subsets, blast
      transformation to antigens including, phytohemagglutinin, PPD, pokeweed, and
      purified human aortal antigen (PHAA) were examined. Soluble protein from human
      aorta was fractionated into 9 peaks by DEASE-52 and Sephadex G-75 chromatography,
      and 25 micrograms of major protein fraction-II was used for blast transformation
      study. Blast transformation by PHAA was higher in Takayasu arteritis as compared
      to all other groups (P < 0.05). Blast transformation to PPD showed wide variation
      in all the groups, and was significantly higher only in tuberculin reactors as
      compared to controls. These observations support aortal sensitization to PHAA
      playing a role in pathogenesis of Takayasu arteritis and do not relate
      tuberculosis to Takayasu arteritis, at least immunologically. In addition, the
      ratio of CD-4 positive to CD-8 positive lymphocytes changing in favor of the
      former and the concomitant increase in B lymphocytes favor the presence of
      autoimmune disturbances in Takayasu arteritis.

PMID- 1360980
TI  - Angiographic characteristics of Takayasu arteritis.

PMID- 1360979
TI  - Takayasu arteritis in Korean children: clinical report of seventy cases.
AB  - Seventy cases of Takayasu arteritis in Korean children are reported. There were
      57 females and 13 males (male-to-female ratio; 1:4.4). The youngest patient was a
      3-year-old female. Family history was positive in one patient. The most common
      chief complaints on admission were dyspnea, headache, palpitation, and edema
      which were due to hypertension and congestive heart failure. Hypertension was
      seen in 65 out of 70 patients (92.8%). The abdominal aorta, thoracic aorta, and
      renal arteries were the most commonly involved sites in these children. Two
      patients had nephrotic syndrome. The frequency of positive tuberculin reaction
      was much higher in children with Takayasu arteritis compared with the general
      population, and the intensity of the reaction was also stronger. The majority of
      the patients required immediate medical treatment to control congestive heart
      failure due to hypertension at initial presentation. When ESR was elevated,
      corticosteroid was administered. Surgical treatment showed good results in six
      out of ten cases. Percutaneous intraluminal angioplasty was effective for
      lowering the blood pressure in six out of nine cases. In three cases, restenosis
      occurred and angioplasty was repeated in two cases.

PMID- 1360981
TI  - Modulation of P-glycoprotein-mediated drug transport by alterations in lipid
      fluidity of rat liver canalicular membrane vesicles.
AB  - P-glycoprotein (P-gp) is believed to function as an ATP-dependent efflux pump for
      natural product anti-cancer drugs in multidrug-resistant (MDR) tumor cells and in
      certain normal tissues. P-gp has been localized to the apical plasma membrane of
      the bile canaliculus where it has been shown to transport [3H]daunomycin. In this
      study, we investigated whether alterations in membrane lipid fluidity of
      canalicular membrane vesicles (CMV) could modulate the P-gp-mediated accumulation
      of [3H]daunomycin and [3H]vinblastine. Accumulation of both cytotoxic agents was
      stimulated by ATP, exhibited temperature dependence and osmotic sensitivity, and
      followed Michaelis-Menten kinetics. Alterations in CMV lipid fluidity were
      induced by the known fluidizers, 2-(2-methoxyethoxy)ethyl 8-(cis-2-n
      octylcyclopropyl)octanoate (A2C) and benzyl alcohol, and were assessed by
      fluorescence polarization techniques using the fluorescent probe, 1,6-diphenyl
      1,3,5-hexatriene (DPH). Both A2C (2.5-5.0 microM) and benzyl alcohol (10-20 mM)
      produced a dose-dependent increase in CMV lipid fluidity. Moreover, both
      fluidizers, at the above doses, significantly inhibited (p < 0.05) the ATP
      dependent accumulation of [3H]daunomycin. [3H]Vinblastine accumulation was also
      inhibited by A2C (p < 0.05). Lower doses of A2C (0.6 microM) and benzyl alcohol
      (1 mM) failed to influence either lipid fluidity or P-gp-mediated drug
      accumulation. Kinetic analysis revealed that A2C (5.0 microM) noncompetitively
      inhibited [3H]daunomycin accumulation and uncompetitively inhibited
      [3H]vinblastine accumulation with apparent Ki values of approximately 1.5 and
      approximately 1.2 microM, respectively. Verapamil competitively inhibited P-gp
      mediated accumulation of [3H]daunomycin but failed to alter the fluidity of CMV.
      Taken together, the present results demonstrate that while increases in membrane
      fluidity of CMV are not necessarily required to inhibit P-gp-mediated drug
      accumulation, they can inhibit these processes, at least in CMV. Alterations in
      the physical state of CMV, therefore, appear to be at least one important
      modulator of P-gp function.

PMID- 1360982
TI  - Identification of glutamic acid 105 at the active site of Bacillus
      amyloliquefaciens 1,3-1,4-beta-D-glucan 4-glucanohydrolase using epoxide-based
      inhibitors.
AB  - Bacillus amyloliquefaciens 1,3-1,4-beta-D-glucan 4-glucanohydrolase (EC 3.2.1.73)
      was modified by the mechanism-based, affinity-labeling reagent [14C](3,4)
      epoxybutyl beta-D-cellobioside. Following partial inactivation a completely
      inactivated enzyme preparation containing 1.1 mol of covalently bound
      inhibitor/mol of protein was obtained by chromatography on a cellulosic matrix.
      The inactivated enzyme was digested with endoproteinase Glu-C and radioactive
      peptides purified by reversed-phase high performance liquid chromatography
      (HPLC). The affinity label was esterified exclusively to the gamma-carboxylate of
      Glu105 in the sequence Gly-Thr-Pro-Trp-Asp-Glu-Ile-Asp-Ile-Glu109. The sequence
      motif Glu-(Ile/Leu)-Asp-Ile is found in many glucanases and xylanases and may
      therefore serve to identify the catalytic nucleophile in beta-glycanases, which
      otherwise exhibit a low degree of sequence identity. The esterification of Glu105
      by the affinity label abolished endoproteinase Glu-C-mediated hydrolysis of the
      Glu-Ile106 peptide bond. Identification of phenylthiohydantoin-Glu105 during
      automated sequence analysis was not possible unless the affinity label was
      liberated by prior base hydrolysis. These observations formed the basis for the
      development of a highly sensitive approach for the identification of catalytic
      carboxylates in polysaccharide hydrolases employing non-radioactive inhibitors,
      comparative HPLC mapping, electrospray mass spectrometry, and Edman degradation.

PMID- 1360984
TI  - Alpbach workshop on the dynamics of motile systems, 4-10 April 1992.

PMID- 1360983
TI  - Identification of residues in the first cytoplasmic loop of P-glycoprotein
      involved in the function of chimeric human MDR1-MDR2 transporters.
AB  - The human MDR1 gene encodes the multidrug transporter (P-glycoprotein), a
      multidrug efflux pump. The highly homologous MDR2 gene product does not appear to
      be a functional multidrug pump. We have constructed a chimeric protein in which
      the first intracytoplasmic loop and the third and fourth transmembrane domains of
      the MDR1 protein were replaced by the analogous region of MDR2. Substitution of
      the MDR2 sequences encompassing amino acid residues 140 to 229 resulted in 17
      amino acid changes, 10 in the intracytoplasmic loop (amino acids 141-188) and 7
      in the transmembrane regions. This chimeric protein was expressed on the surface
      of NIH 3T3 cells where it bound [3H]azidopine but did not confer drug resistance.
      When only 4 residues, 165, 166, 168, and 169, were changed back to MDR1 amino
      acids, a functional drug transporter was recovered. When residues 165, 166, 168,
      and 169 from MDR2 were substituted into a functional MDR1 cDNA, the resulting
      construction was not able to confer drug resistance. These results indicate that
      the major functional differences between MDR1 and MDR2 in this region of P
      glycoprotein reside in a small segment of the first intracytoplasmic loop. We
      also independently analyzed the effect of replacing Asn183 of MDR1 with Ser which
      occurs in MDR2. Substitution of Ser at position 183 in combination with Val at
      position 185 in P-glycoprotein resulted in a relative increase in resistance to
      actinomycin D, vinblastine, and doxorubicin in transfected NIH 3T3 cells. These
      results emphasize the importance of the first intracytoplasmic loop in P
      glycoprotein in determining function and relative drug specificity of the
      transporter.

PMID- 1360985
TI  - An analysis of response prevention and flooding procedures in the treatment of
      adolescent obsessive compulsive disorder.
AB  - Flooding and response prevention have been widely used in the treatment of adult
      obsessive compulsive disorder but have been overlooked in favor of less
      restrictive procedures when treating children. The present case investigates the
      utility of these procedures in an adolescent with severe compulsive handwashing.
      Treatments were introduced hierarchically to minimize subject distress; graded
      exposure decreased the frequency of handwashing, but flooding was required to
      eliminate the compulsion. Guidelines for the ethical use of flooding and exposure
      therapies with children are offered.

PMID- 1360987
TI  - Growth properties of larval and adult locust neurons in primary cell culture.
AB  - We developed a cell culture system for thoracic neurons of fifth instar or adult
      locusts (Locusta migratoria) in order to obtain maximum visualization of cellular
      morphology and direct access to the neurons for electrophysiological analysis.
      The dissociated neurons regenerated new neurites in a serum-free defined culture
      medium, in which they remained viable for up to 3 weeks. Viability of the cells
      was confirmed by intracellular recordings demonstrating active membrane
      properties and action potentials. While the morphology of the cultured neurons is
      distinct from their in vivo counterparts, they retained some cellular surface
      properties and markers related to transmitter metabolism. Two factors influencing
      cellular morphology in vitro were identified in Locusta: 1) the presence of a
      primary neurite stump, and 2) membrane contacts between cells. Dissociated
      neurons of the locust species Schistocerca gregaria grown in a hemolymph-enriched
      medium showed a marked reduction in branching patterns and a tenfold increase in
      neurite length compared to neurons growing in a medium without hemolymph. This
      culture system could prove useful for identifying the action of hemolymph-derived
      growth factors.

PMID- 1360986
TI  - Patterns of glutamate, glycine, and GABA immunolabeling in four synaptic terminal
      classes in the lateral superior olive of the guinea pig.
AB  - The goal of this study was to correlate synaptic ultrastructure with transmitter
      specificity and function in the lateral superior olive (LSO), a nucleus that is
      thought to play a major role in sound localization. This was accomplished by
      means of postembedding immunogold immunocytochemistry. Four classes of synaptic
      terminals were identified in the LSO. They were distinguishable from one another
      both morphologically and on the basis of their different patterns of
      immunolabeling for glutamate, glycine, and gamma-aminobutyric acid (GABA). The
      highest level of glutamate immunoreactivity was found in terminals that contained
      round vesicles (R) and formed synaptic contacts with asymmetric synaptic
      junctions. Round-vesicle terminals predominated on small caliber dendrites by a
      ratio of at least 2:1 over the other classes combined. The thinnest dendrites
      were typically contacted by R terminals only. The ratio of R terminals to the
      other types decreased as the caliber of the dendritic profiles they apposed
      increased so that on the soma, R terminals were outnumbered by at least 2:1 by
      the other types. Terminals containing flattened vesicles (F) exhibited intense
      immunoreactivity for both glycine and glutamate, although the glutamate
      immunolabeling was not as high as that in the R terminals. Flattened-vesicle
      terminals formed symmetric synaptic contacts with their targets and their
      distribution was the reverse of that described for R terminals; i.e., they were
      most abundant on LSO perikarya and fewest on small caliber dendrites. Two
      terminal types, both containing pleomorphic vesicles and forming symmetric
      synaptic junctions, were found in far fewer numbers. One group contained large
      pleomorphic vesicles (LP) and was immunoreactive for both glycine and GABA. The
      other group contained small pleomorphic vesicles (SP) along with a few dense-core
      vesicles and labeled for GABA only. The LP terminals were preferentially
      distributed on somata and large-caliber dendrites, while the SP terminals most
      often contacted smaller dendrites. Previous work suggests that a large percentage
      of the R terminals arise from spherical cells in the ipsilateral cochlear nucleus
      and are excitatory in action. This pathway may use glutamate as a transmitter.
      Many of the F terminals are thought to originate from the ipsilateral medial
      nucleus of the trapezoid body and appear to be the inhibitory (glycinergic)
      terminals from a pathway that originates from the contralateral ear. The origins
      and functions of LP and SP terminals are unknown, but a few possibilities are
      discussed along with the significance of cocontainment of neuroactive substances
      in specific terminal types.

PMID- 1360988
TI  - Retinoids: Present and future. Proceedings of a symposium at the 18th World
      Congress of Dermatology. New York, New York, June 16, 1992.

PMID- 1360989
TI  - Comorbidity of anxiety and depression in youth: treatment implications.
AB  - Reviews the empirical literature on the comorbidity of anxiety and depressive
      disorders in youth, emphasizing prevalence of comorbidity, difficulties in
      assessment and measurement, familial factors, and developmental differences. The
      nature of anxiety and of depression in youth is examined (e.g., differentiating
      cognitive deficiencies from cognitive distortions), and treatment recommendations
      are presented from a cognitive-behavioral framework. Components of the treatment
      include affective education, enactive programming, addressing reinforcement
      difficulties, correcting cognitive distortions, and enhancing problem-solving
      skills. Peer and familial factors are discussed. Successful treatment of co
      morbid children relies on a flexible application of these strategies with
      consideration of the developmental level and particular symptom constellation of
      the individual child.

PMID- 1360990
TI  - Attention-deficit hyperactivity and conduct disorder: comorbidity and
      implications for treatment.
AB  - The distinguishing and overlapping features of attention-deficit hyperactivity
      disorder (ADHD) and conduct disorder (CD) are discussed. Conclusions regarding
      comorbidity, treatment efficacy, and long-term outcome can be influenced by
      several factors, including diagnostic procedures and sample characteristics. The
      need to distinguish between referred and non-referred samples is particularly
      crucial when considering treatment and comorbidity issues. The efficacy of
      psychosocial and pharmacological treatments in ADHD and CD children is reviewed
      as are the few studies of psychostimulant medication in co-morbid youngsters.
      Suggestions regarding treatment planning and recommendations for treatment and
      research are described.

PMID- 1360992
TI  - Intranasal Anticholinergic Treatment of Nasal Disorders. San Francisco,
      California, March 6, 1991.

PMID- 1360991
TI  - The effects of phenindamine tartrate on sleepiness and psychomotor performance.
AB  - Phenindamine, an H1-receptor antagonist that was developed almost 50 years ago,
      has been associated with both drowsiness and insomnia. Since its central nervous
      system profile has not been well characterized, we used a series of psychomotor
      tests to conduct two studies. In the first, 12 subjects received single oral
      doses of phenindamine (25 mg), diphenhydramine (50 mg), terfenadine (60 mg), or
      placebo in a four-way crossover study. Psychomotor tests included choice reaction
      time (CRT), tracking, and hand steadiness (HS). In the second trial, 15 subjects
      received single oral doses of phenindamine (25 mg), pseudoephedrine (60 mg),
      phenindamine and pseudoephedrine, diphenhydramine (50 mg), or placebo in a five
      way crossover study. Psychomotor tests included CRT, HS, and a task that divided
      attention between tracking and reaction time. Introspective drowsiness was
      measured in both trials with use of a visual analog scale (VAS) and the Stanford
      Sleepiness Scale (SSS). All assessments were made before and 1, 3, and 5 hours
      after drug administration. In the first trial, diphenhydramine produced
      significant impairment relative to placebo (p < 0.05) in CRT, tracking, and HS
      tasks and higher SSS and VAS scores, with peak effect noted at 3 hours.
      Phenindamine did not significantly differ from placebo or terfenadine. In the
      second trial, diphenhydramine produced significant impairment relative to placebo
      (p < 0.05) in CRT, divided attention, HS, and VAS, and SSS, also peaking at 3
      hours. Stanford Sleepiness Scale scores after phenindamine were greater than
      placebo at 3 hours (p < 0.05) but significantly less than diphenhydramine (p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1360993
TI  - Distribution of sympathetic neuroeffector junctions in the juxtaglomerular region
      of the rabbit kidney.
AB  - Two structurally distinct types of sympathetic axon (Type I and Type II) have
      recently been identified in the renal cortex of the rat and the rabbit. This
      study describes the distribution and density of the neuroeffector junctions made
      by these two types of axon on the different tissues from the juxtaglomerular
      region of the rabbit renal cortex. Immunohistochemical studies showed that
      tyrosine hydroxylase-positive axons were located only in regions adjacent to the
      arteries and arterioles in the renal cortex. Ultrastructural studies of the
      juxtaglomerular region indicated that both types of axon formed junctions on
      vascular smooth muscle cells, epithelial cells of proximal tubules and renin
      secreting granular epithelioid cells. The density of neuromuscular junctions (18
      x 10(3)/mm2 of vessel surface) was more than twice as high on the afferent
      arteriole as on the efferent arteriole or proximal tubules immediately adjacent
      to the glomerular arterioles (both about 6 x 10(3)/mm2). The junction density on
      granular epithelioid cells was much lower (about 2 x 10(3)/mm2) and were rarely
      observed on the distal tubule. Afferent arterioles preferentially received
      junctions from Type I axons at a relatively high density (14.2 x 10(3)/mm2)
      whereas junctions formed by Type II axons were less selectively distributed and
      occurred at lower densities on all other tissues (range, 1-6.3 x 10(3)/mm2).
      Presynaptic membrane specialisations were identified only at junctions on
      arterioles and granular epithelioid cells and occurred more frequently at Type I
      than at Type II junctions. The data suggest that the predominant effect of the
      sympathetic innervation in the juxtaglomerular region of the renal cortex is on
      the afferent arteriole and that the two axon types within the kidney may have
      different functions.

PMID- 1360994
TI  - IL-12 augments antigen-dependent proliferation of activated T lymphocytes.
AB  - Ag-dependent T cell activation requires multiple transmembrane signals including
      activation of Ag-specific T cell receptor in combination with signals delivered
      through cytokine receptors. IL-12 is a heterodimeric cytokine involved in the
      regulation of NK and T lymphocyte responses. In examining the role of IL-12 in T
      cell activation, we found a direct relationship between Ag stimulation and IL-12
      induced proliferation. Unlike IL-2, which induced proliferation of CTL either in
      the presence or absence of a CD3/TCR co-signal, IL-12 mediated proliferation of
      CTL only when the cells were recently co-stimulated with alloantigen or solid
      phase anti-CD3 antibody. After culture in the absence of alloantigen or anti-CD3
      for 7 to 14 days, these CTL lost the ability to proliferate to IL-12 alone. Under
      these conditions, however, IL-12 synergized with low-dose IL-2 to induce CTL
      proliferation. Restimulation with alloantigen or solid-phase anti-CD3 restored
      the ability of the CTL to proliferate to IL-12 alone. Not all Ag signals resulted
      in IL-2 independent proliferation to IL-12. For example, CTL with specificity for
      influenza matrix peptide proliferated best when co-cultured with peptide Ag
      presented on self MHC and a combination of IL-2 and IL-12. This evidence suggests
      that IL-12 may be useful in expanding an Ag-specific T cell population, as the
      culture of CTL with IL-12 and low-dose IL-2 leads to proliferation only in
      response to an Ag co-signal.

PMID- 1360995
TI  - Costimulation of T cell receptor/CD3-mediated activation of resting human CD4+ T
      cells by leukocyte function-associated antigen-1 ligand intercellular cell
      adhesion molecule-1 involves prolonged inositol phospholipid hydrolysis and
      sustained increase of intracellular Ca2+ levels.
AB  - Activation of resting human CD4+ T cells mediated by mAb ligation of the TCR/CD3
      complex requires costimulatory signals to result in proliferation; these can be
      provided by intercellular cell adhesion molecule-1 (ICAM-1, CD54) a natural
      ligand of leukocyte function-associated Ag-1 (LFA-1, CD11a/CD18). We analyzed
      early signaling events involved in T cell activation to determine the
      contribution by the LFA-1/ICAM-1 interaction. We studied in detail the hydrolysis
      of phosphatidylinositol(4,5)bisphosphate and intracellular levels of free Ca2+
      during stimulation with beads coated with the CD3 mAb OKT3 alone or in
      combination with purified ICAM-1 protein. Our investigations show no response to
      LFA-1/ICAM-1 alone, but that costimulation by LFA-1/CAM-1 interaction induces
      prolonged inositol phospholipid hydrolysis (up to 4 h), resulting in generation
      of both inositol(1,4,5)phosphate3 and inositol(1,3,4,5)phosphate4 and their
      derivatives. Based on studies with cycloheximide, this costimulatory effect of
      prolonged inositol phospholipid hydrolysis appears dependent in part on de novo
      protein synthesis. A sustained increase in intracellular levels of free Ca2+
      level is also observed after LFA-1/ICAM-1 costimulation, which is at least partly
      dependent on extracellular sources of Ca2+. Kinetic studies indicate that
      costimulation requires a minimal period of 4 h of LFA-1/ICAM-1 interaction to
      provide maximal costimulation for OKT3-mediated T cell proliferation. Thus, the
      necessary costimulation required for OKT3-mediated proliferation in this model
      system may be provided by an extended LFA-1/ICAM-1 interaction that in
      combination with OKT3 mAb leads to signal-transducing events, resulting in
      prolonged phospholipase C activation and phosphatidylinositol(4,5)bisphosphate
      hydrolysis, and a sustained increase in intracellular levels of free Ca2+.

PMID- 1360996
TI  - Lipopolysaccharide increases glucocorticoid receptor expression in murine
      macrophages. A possible mechanism for glucocorticoid-mediated suppression of
      endotoxicity.
AB  - In a previous study we demonstrated that IFN-gamma induced an increase in the
      number of glucocorticoid receptors (GR) in murine macrophages. To examine further
      the environmental signals involved in regulation of macrophage GR availability,
      we asked whether another classical macrophage-activating factor, LPS, would
      induce an increase in GR number in the macrophage cell line, RAW 264.7, and in
      primary macrophages from C3H mice. We report that treatment of RAW 264.7 cells
      and peritoneal exudate macrophages from C3H/OuJ mice with protein-free, phenol
      water-extracted LPS (PW-LPS) induced an increase in the number of GR. A
      significant increase in GR number was observed as early as 4 h after PW-LPS
      treatment, was maximal at 12 h, and remained heightened through 48 h. Optimal
      induction of the GR by PW-LPS was observed when murine macrophages were treated
      with 10 ng/ml of PW-LPS. The LPS-induced increase in macrophage GR number could
      be inhibited by polymyxin B. Macrophages obtained from the LPS hyporesponsive
      C3H/HeJ strain did not respond to PW-LPS, but did respond to protein-rich,
      butanol-extracted LPS with a modest increase in GR number after treatment with 2
      micrograms/ml. Moreover, taxol, an antineoplastic agent with LPS mimetic
      activity, also increased GR number in murine macrophages. These results suggest
      that LPS is not only an important macrophage-activating signal, but may also be
      important in sensitizing the cell for negative regulatory events such as feedback
      inhibition by glucocorticoids.

PMID- 1360997
TI  - Differential expression of VLA-alpha 4 and VLA-beta 1 discriminates multiple
      subsets of CD4+CD45R0+ "memory" T cells.
AB  - Given the importance of adhesion in T cell development, we have undertaken
      systematic flow cytometric analysis of CD4 T cells to determine relationships
      between the developmentally regulated marker CD45R0 and adhesion receptors (five
      VLA integrin chains). The most important findings are that: 1) expression of
      alpha 3, alpha 5, and alpha 6 are closely coregulated with beta 1 on CD4 cells,
      while regulation of VLA-alpha 4 is quite discordant. 2) CD45R0- cells, generally
      understood to be naive cells, have low homogeneous expression of VLA-alpha 3, VLA
      alpha 4, VLA-alpha 5, VLA-alpha 6, and beta 1 integrin chains; studies of cord
      blood CD4 cells confirm the low homogeneous expression of alpha 4 and beta 1 on
      naive cells. 3) In marked contrast, CD45R0+ cells, generally understood to be
      memory cells, show not only an overall increase in expression of these integrins
      (relative to CD45R0- cells) but also heterogeneity. Dramatic heterogeneity is
      revealed when the markers VLA-alpha 4 and beta 1 are analyzed together. Many
      CD45R0+ cells show increased levels of both VLA-alpha 4 and VLA-beta 1; however,
      some have increased levels principally of either VLA-beta 1 or VLA-alpha 4. We
      hypothesize that T cells becoming memory cells in different microenvironments
      specialize their integrin phenotype, thereby acquiring distinctive functional and
      homing capacities; in this process, VLA-4 (CD49d) appears to play a unique role.

PMID- 1360998
TI  - Takayasu's arteritis: anatomic change before and after steroid therapy evaluated
      by angiography and echo-Doppler color-flow.
AB  - A 36-year-old Italian woman with active Takayasu's disease presented a bilateral
      occlusions of subclavian artery and stenosis of bilateral common carotid
      arteries: the maximal diameter stenosis, measured with echo-Doppler color-flow
      (EDCF) in the longitudinal section was of 43.5 +/- 2.4% on the right and 61 +/-
      1.4% on the left. Prednisolone was administered for 30 months at doses from 25 to
      6 mg daily (12.5 mg every two days). During steroid therapy we could monitor by
      EDCF the anatomic change of the involved vessel and a final decrease in carotid
      wall thickening of 19.8% on the left and 14.0% on the right side. This work
      demonstrates for the first time that duplex sonography may be an useful tool to
      asses possible anatomic changes in the carotid lesions of Takayasu's arteritis in
      response to steroid therapy.

PMID- 1360999
TI  - Characterization of Dobrava virus: a Hantavirus from Slovenia, Yugoslavia.
AB  - Small mammals were collected in natural foci of hemorrhagic fever with renal
      syndrome (HFRS) in Slovenia, Yugoslavia, and a hantavirus was isolated from the
      lungs of an Apodemus flavicol lis captured in Dobrava village. This new isolate,
      Dobrava virus, was compared with representative strains of the Hantavirus genus
      by serological and polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) methods. It was found by cross immunofluorescent and
      enzyme-linked immunosorbent assays that antigenic properties of Dobrava virus
      were different from those of other hantaviruses. The RNA of this virus was
      successfully amplified with hantavirus genus reactive primer sets by reverse
      transcriptase polymerase chain reaction (RT-PCR); however, PCR-RFLP analysis of
      the amplified product was shown to be unique among those of the known
      hantaviruses, further indicating that Dobrava virus represents a new hantavirus
      serotype.

PMID- 1361000
TI  - The paired domain-containing nuclear factor pax[b] is expressed in specific
      commissural interneurons in zebrafish embryos.
AB  - The zebrafish paired box (Pax) genes are expressed in the early neural tube and
      are thought to be transcription factors that regulate the differentiation of
      cells in the central nervous system (CNS). The protein product of one of these
      Pax genes, pax[b], is detectable as a nuclear antigen in all the regions of the
      embryo that transcribe the gene including the posterior midbrain, the nephritic
      primordium, the Wolffian duct, the optic stalk, and, in specific neurons, in the
      hindbrain and spinal cord. The timing and pattern of axonal outgrowth by the
      early pax[b]-positive neurons suggest that they are the commissural secondary
      ascending (CoSA) interneurons in the spinal cord; the primary commissural
      interneurons (MiD2c and MiD3c) in hindbrain rhombomeres mi2 and mi3; and a
      previously unclassified set of commissural interneurons that we termed the
      commissural caudalrhombomere ascending (CoCaA) interneurons in the caudal
      hindbrain. In contrast, the Mauthner interneurons do not express pax[b] early in
      development. Shortly after the appearance of the first pax[b]-positive
      interneurons, additional nuclei adjacent to the first pax[b]-positive
      interneurons become pax[b] positive. This pattern of expression suggests that the
      pax[b] protein may be involved in determining the identity of specific
      commissural interneurons.

PMID- 1361002
TI  - Detection of fimbrilin gene (fimA) in Porphyromonas (Bacteroides) gingivalis by
      Southern blot analysis.

PMID- 1361001
TI  - Delay in fixation does not affect the immunoreactivity of proliferating cell
      nuclear antigen (PCNA).
AB  - The effect of delayed fixation on the immunoreactivity of proliferating cell
      nuclear antigen (PCNA) was investigated using eight breast carcinomas.
      Topologically shuffled samples of each tumour were immersed in fixative at times
      of 0.5, 1, 2, 4, 6, 18, and 24 h after surgical removal. In addition to a PCNA
      index (percentage of positive cells per 1200 tumour cells), a semi-quantitative
      PCNA grading system was used, based on estimates of more than or less than 50 per
      cent of positive tumour cells at each time interval. The PCNA index of six
      tumours increased by a mean of 10 per cent with a fixation delay of 24 h. The
      PCNA grade of all eight tumours showed no change with delayed fixation.

PMID- 1361003
TI  - British Pharmaceutical Conference 1992. Science proceedings, 129th meeting.
      Birmingham, September 7-10, 1992. Abstracts.

PMID- 1361004
TI  - Phenotypic and functional analysis of peripheral blood lymphocytes in oral lichen
      planus.
AB  - To assess cellular immunity in oral lichen planus (OLP), peripheral blood
      mononuclear cells (PBMC) were obtained from 19 OLP patients and 30 control
      subjects. The proportions of circulating CD45RA+ and CD29+ lymphocyte subsets
      were determined. The proliferative activity of PBMC to the non-specific plant
      mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) was examined
      together with the spontaneous proliferative response and the response in the
      autologous mixed lymphocyte reaction (AMLR). In the OLP group, the proportion of
      CD4+ CD45RA+ T lymphocytes was significantly less than control subjects and the
      proportion of CD4+ CD29+ T lymphocytes was increased significantly. The
      proliferative response to PHA was similar in OLP and controls subjects. Con A
      stimulated PBMC proliferation was decreased significantly in the OLP group.
      Spontaneous PBMC proliferation in patients with non-reticular lesions was
      significantly less than control subjects. Despite a mildly depressed response in
      the AMLR in OLP patients, this result was not statistically significant. Results
      of the phenotypic analysis of peripheral blood lymphocytes indicate a decreased
      proportion of naive T cells and an increased proportion of primed memory T cells,
      although the antigen specificity of these memory cells remains to be determined.
      Results of the functional assays would seem to reflect this phenotypic shift, and
      as T cells responding to Con A stimulation and in the AMLR possess suppressor
      inducer activity, these results may also suggest an association between OLP and
      defective innate T cell-mediated suppressor circuits.

PMID- 1361005
TI  - Rare expression of the c-erbB-2 oncoprotein in salivary gland tumors: an
      immunohistochemical study.
AB  - An immunohistochemical study of c-erbB-2 oncoprotein expression was carried out
      on 201 cases of primary salivary gland tumors, using a polyclonal antibody,
      raised to the intracytoplasmic domain of the c-erbB-2 oncogene product. An
      intense membrane reactivity was observed in one case of sialocarcinoma
      transformed from pleomorphic adenoma (n = 8) and one case of mucoepidermoid
      carcinoma (n = 22). A comparative histopathologic evaluation of c-erbB-2 positive
      tumors showed marked variation in cell size, nuclear pleomorphism,
      multinucleation, a high mitotic rate and increased lymphoid cell infiltration and
      an aggressive clinical course with poor survival. The results indicate that c
      erbB-2 oncoprotein is rarely expressed in malignant salivary gland tumors.
      However, the overexpression appears to have a distinct histopathologic feature,
      but a larger study incorporating histopathology and clinical data would be
      necessary to correlate the significance of c-erbB-2 oncogene product in salivary
      malignant tumors.

PMID- 1361006
TI  - Scanning electron microscopy of eggs of Mansonia bonneae (Diptera: Culicidae).
AB  - The egg of Mansonia bonneae (Edwards) is described by means of scanning electron
      microscopy (SEM) and compared with other sympatric species reported recently in
      previous studies. Ma. bonneae differed from Ma. uniformis (Theobald), Ma. indiana
      (Edwards), Ma. annulifera (Theobald), and Ma. annulata (Leicester) in that it has
      six variably sized dog-tooth spines surrounding the raised central micropyle, and
      only a single nipplelike stud at the anterior one-third of the egg. A key for
      identification of the eggs of the five sympatric Mansonia species under SEM is
      presented.

PMID- 1361007
TI  - Identification of human blood in mosquitoes (Diptera: Culicidae) using
      nonradioactive DNA dot blot hybridization.
AB  - A dot blot hybridization procedure was developed to detect human blood meals in
      engorged mosquitoes. A biotinylated DNA probe allowed the detection of 10-100 ng
      of human DNA, discriminated well between human and nonhuman sources of blood, and
      cross-reacted only with monkey DNA. Results showed that this method was a
      specific and sensitive technique for the identification of blood meals up to 100
      h after ingestion. The nonisotopic label offers easy handling without the
      problems inherent in the use of radioisotopes, and it can be adapted for use in
      routine field tests.

PMID- 1361008
TI  - Liposome-mediated modulation of multidrug resistance in human HL-60 leukemia
      cells.
AB  - BACKGROUND: Multidrug resistance (MDR) is a major obstacle in cancer treatment.
      Resistance of cultured tumor cells to major classes of cytotoxic drugs is
      frequently due to expression of a plasma membrane P-glycoprotein encoded by MDR
      genes. We have demonstrated that liposome-encapsulated doxorubicin is more toxic
      than the free drug and that it modulates MDR in Chinese hamster LZ cells and
      human colon cancer cells. PURPOSE: To investigate further the association between
      expression of P-glycoprotein and modulation of MDR by liposome-encapsulated
      doxorubicin, we studied vincristine-resistant HL-60/VCR leukemia cells, which
      express P-glycoprotein, and doxorubicin-resistant HL-60/ADR leukemia cells, which
      do not. METHODS: Cells were exposed to various concentrations of free doxorubicin
      and liposome-encapsulated doxorubicin. The cellular content of doxorubicin was
      determined by fluorescence analysis, and cytotoxicity was determined by cell
      growth inhibition. Photoaffinity-labeling studies of P-glycoprotein binding were
      performed on HL-60/VCR and HL-60/ADR cells and KB-GSV2 cells transfected with the
      MDR1 gene (also known as PGY1). RESULTS: The concentrations that caused 50%
      inhibition of growth (IC50) for free doxorubicin in HL-60, HL-60/ADR, and HL
      60/VCR cells were 30 nM, 9 microM, and 0.9 microM, respectively. The values for
      liposome-encapsulated doxorubicin in parental HL-60 cells and HL-60/ADR cells
      were 20 nM and 9 microM, respectively, indicating little or no sensitization. In
      contrast, HL-60/VCR cells were fivefold more sensitive to liposome-encapsulated
      doxorubicin than to free doxorubicin, and IC50 was reduced to 0.17 microM. In HL
      60 cells exposed to liposome-encapsulated doxorubicin, intracellular doxorubicin
      accumulation was less than that seen with free drug. In contrast, in HL-60/VCR
      cells, accumulation was twofold to threefold higher than that with free
      doxorubicin. Liposome-encapsulated doxorubicin completely inhibited the
      photoaffinity labeling of P-glycoprotein by azidopine in membrane vesicles of HL
      60/VCR cells, with a potency comparable to that of azidopine, suggesting that
      circumvention of MDR by liposomes is related to their specific interaction with P
      glycoprotein. The studies with KB-GSV2 cells indicated that blank liposomes can
      directly inhibit photoaffinity labeling of P-glycoprotein. CONCLUSIONS: These
      results demonstrate the effectiveness of liposome-encapsulated doxorubicin in
      overcoming resistance in the multidrug-resistant phenotype of HL-60/VCR cells by
      direct interaction with P-glycoprotein. Furthermore, they indicate that liposome
      encapsulated doxorubicin may be an effective treatment for human cancers.

PMID- 1361009
TI  - Cerebral ammonia levels and enzyme changes during Plasmodium yoelii infection in
      mice.
AB  - Ammonia, lactate and glutamate levels and the activities of glutamine synthetase
      (GS), glutamate dehydrogenase (GDH), glutaminase (GLN), aspartate transaminase
      (AST), phosphofructokinase (PFK) and monoamine oxidase (MAO) were compared in the
      brain tissue of normal and P. yoelii infected mice. The brain lactate increased
      by 96% at peak parasitaemia. Cerebral ammonia also exhibited an increase in
      infected mice which was parasitaemia dependent, while glutamate remained almost
      unchanged. The brain glutamine synthetase registered an increase of 35% (P <
      0.001) in post-mitochondrial fractions, this effect being perceptible even at low
      parasitaemia, but attained constancy at parasitaemia levels higher than 20%. The
      activity of monoamine oxidase and phosphofructokinase increased by 105% (P <
      0.02) and 41% (P < 0.05) respectively while glutamate dehydrogenase decreased by
      15% (P < 0.001). Glutaminase and aspartate transaminase were not significantly
      influenced by infection (tested only at high parasitaemia levels). It has been
      postulated that cerebral hypoxia and aberrations in ammonia metabolism may both
      contribute towards malaria induced cerebral complications.

PMID- 1361010
TI  - [Clinical significance of posttetanic count (PTC) during onset and spontaneous
      offset of neuromuscular blockade induced by vecuronium].
AB  - To compare the clinical difference of posttetanic count (PTC) during onset and
      spontaneous offset, the changes of PTC during an intense neuromuscular blockade
      induced by vecuronium (0.08 mg.kg-1, i.v.) were measured using a neuromuscular
      transmission analyzer in 64 adult patients anesthetized with nitrous oxide and
      halothane. Furthermore, intubation score was evaluated when zero PTC was
      obtained. The obvious movement of diaphragm associated with endotracheal
      intubation was observed in 9 out of 20 patients (45%) even when it was performed
      after obtaining zero PTC. The difference of PTC responses between the onset and
      the offset was found. The difference was that, during the onset, a tetanic
      response was observed obviously and the height of the posttetanic single twitch
      was low, and during offset, even when no response was observed, the height of a
      posttetanic single twitch response was high with the same PTC. These facts
      indicate that the same PTC has different clinical significance during onset and
      offset.

PMID- 1361011
TI  - [Changes in mental workload and fatigue during performance of a mental task. 1.
      An experiment in 8-h self-paced transcribing task].
AB  - The changes in mental workload and fatigue during a one-day transcribing task
      were examined by determining some subjective and physiological measures which
      reflect mental activity. With an interval of one week between the three test
      days, 12 male students rested and performed self-paced transcribing task with
      moderate and maximum effort for 8 h each. The subjects transcribed more
      characters in the task with maximum effort than with moderate effort. In both the
      morning and afternoon, adrenaline excretion increased and heart rate decreased
      with the lapse of time. In linear proportion to the total working hours,
      occipital midline beta-2 amplitude, subjective rating of tiredness and subjective
      symptoms of fatigue rose, but critical flicker values fell slightly in the task
      with maximum effort. It was inferred from these results that with lapse of
      working hours intellectual activity and feeling of fatigue increase and the level
      of arousal slightly declines. Hence, it was considered that mental workload
      becomes heavier and subjective feeling of fatigue increases as the working hours
      become longer.

PMID- 1361012
TI  - Protective effect of minaprine against the abnormal changes of 2-deoxyglucose
      uptake by rat hippocampal slices induced by hypoxia/hypoglycemia.
AB  - Effect of minaprine on hypoxia- or hypoxia/hypoglycemia (ischemia)-induced
      impairment of 2-deoxyglucose (2DG) uptake by rat hippocampal slices was
      evaluated. Since minaprine was found to possess both a stimulating effect on
      acetylcholine release and a blocking effect on 5-HT2 receptors, the improving
      effect of minaprine on impaired 2DG uptake was compared to the findings obtained
      with oxotremorine, ketanserin and pentobarbital. Hippocampal slices were exposed
      to 20-min ischemia, and then these slices were returned to oxygenated and glucose
      containing buffer for 6 hr. Ischemia reduced 30 mM KCl-induced 2DG uptake by the
      hippocampus. Pretreatment with minaprine, oxotremorine, pentobarbital and
      ketanserin attenuated the ischemia-induced decline of 2DG uptake. In addition,
      minaprine, oxotremorine and pentobarbital relatively recovered the increase of
      2DG uptake in the hippocampal slices under hypoxia for 45 min. The present
      results suggest that minaprine exerts a neuroprotective action against ischemia
      induced deficit of energy metabolism in vitro.

PMID- 1361014
TI  - [What information about risks of neuroleptics should be given during pregnancy?].

PMID- 1361013
TI  - [Serum adenosine deaminase in human immunodeficiency virus infection. Its
      relationship with CD4+ lymphocytes and beta 2-microglobulin].
AB  - BACKGROUND: The activity of the deaminase adenosine enzyme (ADA) has principally
      been related with the functionalism and replication of the T lymphocytes. Its
      serum behavior and possible clinical use in infection by the human
      immunodeficiency virus type 1 (HIV-1) was studied. METHODS: A multicenter study
      in which the serum values of ADA were examined and compared with those of two
      reference markers (CD4+ lymphocytes and beta 2-microglobulin) in 35 presumably
      healthy donors used as controls, in 60 intravenous drug users (IVDU) seronegative
      for HIV-1, in 69 HIV-1 asymptomatic seropositive intravenous drug users (HIV-1+)
      and in 48 patients with AIDS. RESULTS: The serum values of ADA were as follows:
      control group 10.9 +/- 4.2 U/I; IVDU group 17.6 +/- 7.4 U/I; asymptomatic HIV-1+
      group 32.7 +/- 10.2 U/I, AIDS group 46.2 +/- 18.2 U/I. Differences between the
      different groups were statistically significant in themselves and in relation to
      the control group. A negative correlation was observed (r = 0.47, p < 0.01) with
      the number of CD4+ lymphocytes and a positive correlation was found with respect
      to beta 2-microglobulin (r = 0.76, p < 0.001). The values of serum ADA activity
      in patients with AIDS and tuberculosis (47.4 +/- 17.2 U/I) were not significantly
      higher (p < 0.05) to those of patients with AIDS without this second infection
      (45.9 +/- 19.3 U/I). CONCLUSIONS: Serum deaminase adenosine may be a useful
      evolutive marker for human immunodeficiency virus type 1 given that its activity
      increases significantly in infected patients in agreement with the grade of
      immunodeficiency and its values correlate well with those of reference markers
      (CD4+ lymphocytes and beta 2-microglobulin).

PMID- 1361015
TI  - [Causal connection between severe throat infection and sudden development of
      cardiac syncope].

PMID- 1361016
TI  - [How do we choose our food?].

PMID- 1361017
TI  - [Put the child in supine position already after a week--recommendation for
      prevention of sudden infant death].

PMID- 1361018
TI  - [An international symposium on torture reflected ethical problems of the host
      country].

PMID- 1361019
TI  - Proceedings of the 1st Forum Ampere on Magnetic Resonance New Methodologies:
      Impact on Industrial Research. Rome, Italy, 21-23 November 1991.

PMID- 1361020
TI  - Application of magnetic resonance imaging to the measurement of neurodegeneration
      in rat brain: MRI data correlate strongly with histology and enzymatic analysis.
AB  - Focal brain ischemia was induced by middle cerebral artery occlusion in the rat.
      The volume of cerebral damage was determined 2 days later by MRI in vivo and in
      the same animals histologically. The edema volume as measured by MRI and the
      histologically determined infarction was highly correlated. As a consequence, the
      neuroprotective effect of the N-methyl-D-aspartate (NMDA) receptor antagonists
      CGP 40116 and MK 801 were similar with both methods. Excitotoxic
      neurodegeneration in the rat striatum was induced by direct injection of
      quinolinic acid. The degree of damage was evaluated in vivo 1 day later by
      quantitative MRI, and 7 days later by measuring the activities of neuronal marker
      enzymes choline acetyltransferase and glutamic acid decarboxylase. Striatal
      damage assessed using the three approaches was highly correlated.
      Cerebroprotective efficacy of the NMDA receptor antagonist CGP 40116 was
      indistinguishable based on all methods. MRI was more reproducible than the
      enzymatic methods and was faster and simpler than histologic examination for
      routine analysis of excitotoxic damage and cerebroprotection in vivo in a
      pharmaceutical research environment.

PMID- 1361021
TI  - In vivo identification and monitoring of changes in rat brain glucose by two
      dimensional shift-correlated 1H NMR spectroscopy.
AB  - Intracerebral glucose resonance was directly detected and resolved in vivo by two
      dimensional shift-correlated (COSY) 1H NMR spectroscopy in anesthetized rats (n =
      4). The relative changes in brain glucose concentration were measured by volume
      integration of the alpha-D-glucose cross peak in the 2D COSY spectra. This report
      demonstrates the possibility of monitoring the variations in cerebral glucose
      following iv injection of glucose.

PMID- 1361023
TI  - [Mucosa-associated immune system in HIV-1 infection. T-cell subpopulations
      compared in different segments of the gastrointestinal tract].
AB  - T-lymphocyte subsets in duodenal, ileal, coecal, colonal, sigmoidal, and rectal
      lamina propria were determined in order to compare the distribution of CD2+,
      CD4+, and CD8+ cell subsets as well as the CD4/CD8 ratio in six different
      compartments of the gastrointestinal tract. In both HIV1-infected and not HIV1
      infected patients, no differences in the distribution of T-lymphocyte subsets
      could be noted between the compartments examined. The HIV1-infected patients
      showed a decrease of CD4+ helper cells and CD4/CD8 ratio and an increase of CD8+
      suppressor/cytotoxic cells in all examined segments. In terms of lamina propria T
      lymphocyte subsets, the intestinal immune system seems to react to HIV1-infection
      homogenously.

PMID- 1361024
TI  - [Prevention of infections in iatrogenic immunosuppression. Specialists' forum.
      Cologne, 13 December 1991].

PMID- 1361022
TI  - Glutamate production in islets of Langerhans: properties of phosphate-activated
      glutaminase.
AB  - Homogenates of rat pancreas, pancreatic islets, and HIT-T15 cells (a clonal line
      derived from B cells) catalyzed the breakdown of glutamine to glutamate. This
      activity was markedly stimulated by the addition of orthophosphate and was much
      greater in homogenates from islets and the B-cell-derived clonal cell line than
      in those from whole pancreas. Islet glutaminase was half-maximally stimulated
      with 40 mmol/L phosphate. Kinetic analyses of the rates of glutamine hydrolysis
      showed that the Vmax for the reaction increased with the increase in phosphate
      concentration, whereas the Km for glutamine (2.6 +/- 0.2 mmol/L) was unaltered.
      The pH optimum for enzyme activity was 8.0 to 8.5 at all phosphate concentrations
      studied. Glutamine breakdown was enhanced by adenosine triphosphate ([ATP]
      approximately 100% at 10 mmol/L) and citrate (approximately 30% at 10 mmol/L),
      but it was unaffected by malate, 2-oxoglutarate, lactate, and ammonia. Glutamate
      significantly inhibited glutamine hydrolysis. Freshly isolated islets had a low
      content of both glutamate and glutamine. After culturing for 1 hour in an amino
      acid-containing medium, the concentrations of glutamine and glutamate increased.
      Subsequent perifusion without amino acids caused a loss of glutamine and a
      concomitant increase in glutamate level. Perifusion with 1 mmol/L glutamine led
      to an increase in both internal glutamine and glutamate. The addition to the
      perifusion medium of either 10 mmol/L glutamine, 10 mmol/L orthophosphate, or
      both substantially enhanced insulin release evoked by 10 mmol/L leucine.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1361025
TI  - Membrane Transport and Signal Transduction. 3rd fall conference of the Membrane
      Biophysical Society. Beaufort, North Carolina, October 5-8, 1991.

PMID- 1361026
TI  - Ammonia regulation of phosphate-activated glutaminase displays regional variation
      and impairment in the brain of aged rats.
AB  - The regulation of PAG by ammonia in whole brain (Sprague-Dawley) and regional
      (Fischer-344) synaptosomal preparations from adult and aged animals was assessed.
      Whole brain synaptosomal preparations from both age groups displayed a
      significant decrease in PAG activity with increasing ammonium chloride
      concentrations, however, the aged rats exhibited a significant attenuation in
      ammonia-induced PAG inhibition. PAG activity measured in synaptosomes prepared
      from the striatum (STR), temporal cortex (TCX) and hippocampus (HIPP) was also
      inhibited by ammonium chloride. The STR showed the greatest degree of ammonia
      induced PAG inhibition (55%) followed by the HIPP (30-35%) and the TCX (25-30%).
      This reduction in PAG activity was significantly attenuated in STR from aged rats
      at ammonium chloride concentrations greater than 50 microM and in the TCX, PAG
      activity was significantly attenuated in the aged rats at ammonia concentrations
      of 0.5 and 1.0 mM. Ammonia regulation of PAG activity in the HIPP appeared to be
      unaffected by age. Ammonium chloride concentrations up to 5 mM had no effect on
      GLU release from cortical slices, although GLN efflux was significantly enhanced.
      These findings suggest that isozymes of PAG may exist in different brain regions
      based on their differential sensitivity to ammonia. The attenuation of ammonia
      induced PAG inhibition seen in aged rats may have deleterious effects in the aged
      brain.

PMID- 1361027
TI  - Guanine nucleotide- and muscarinic agonist-dependent phosphoinositide metabolism
      in synaptoneurosomes from cerebral cortex of immature rats.
AB  - Guanine nucleotide-, neurotransmitter-, and fluoride-stimulated accumulation of
      [3H]inositol phosphates ([3H]InsPs) was measured in [3H]inositol-labeled
      synaptoneurosomes from cerebral cortex of immature (7-day-old) and adult rats, in
      order to clarify the role of GTP-binding proteins (G-proteins) in modulating
      phosphoinositide (PtdIns) metabolism during brain development. GTP(S) [Guanosine
      5'-O-(3-thio)triphosphate] time- and concentration-dependently stimulated PtdIns
      hydrolysis. Its effect was potentiated by full (carbachol, metacholine) and
      partial (oxotremorine) cholinergic agonists through activation of muscarinic
      receptors. The presence of deoxycholate was required to demonstrate agonist
      potentiation of the guanine nucleotide effect. The response to GTP(S) was higher
      in adult than in immature rats, while the effect of cholinergic agonists was
      similar at the two ages examined. At both ages, histamine potentiated the effect
      of GTP(S), while norepinephrine was ineffective. At both ages, guanosine 5'-O-(2
      thio)diphosphate [GDP(S)] and pertussis toxin significantly decreased GTP(S)
      induced [3H]InsPs formation. The phorbol ester phorbol 12-myristate 13-acetate
      (PMA), on the other hand, did not inhibit the guanine nucleotide response in
      synaptoneurosomes from immature rats. NaF mimicked the action of GTP(S) in
      stimulating PtdIns hydrolysis. Its effect was not affected by carbachol and was
      highly synergistic with that of AlCl3, according to the concept that
      fluoroaluminate (AlF4-) is the active stimulatory species. No quantitative
      differences were found in the response to these salts between immature and adult
      animals. These results provide evidence that, in both the immature and adult rat
      brain, neuroreceptor activation is coupled to PtdIns hydrolysis through
      modulatory G-proteins.

PMID- 1361028
TI  - Effect of magnesium on calcium influx activated by glutamate and its agonists in
      cultured cerebellar granule cells.
AB  - The effects of Mg2+ on the glutamate-, kainate-, N-methyl-D-aspartate- and
      quisqualate-induced influx of 45Ca2+ were studied in cultured cerebellar granule
      cells. The N-methyl-D-aspartate- and quisqualate-evoked influx was totally and
      the kainate- and glutamate-evoked influx partially blocked in 1.3 mM
      extracellular Mg2+. The increase in influx induced by kainate, quisqualate and
      glutamate was maximal at 0.1 mM Mg2+, whereas N-methyl-D-aspartate was most
      effective in totally Mg(2+)-free media. D-2-Amino-5-phosphonovalerate blocked
      partially and phencyclidine completely the enhancement of Ca2+ influx by 1 mM
      quisqualate in 0.1-mM Mg2+ medium. The effect of 10 microM quisqualate was also
      significantly inhibited by antagonists specific for different glutamate receptor
      subtypes, including N-methyl-D-aspartate, (RS) alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate and metabotropic receptors. This evidences a heterogeneous
      action of quisqualate, mediated by different glutamate receptor subtypes in 0.1
      mM Mg2+ medium. The efficacy of quisqualate in inducing influx of Ca2+ and the
      selectivity of antagonists for different receptors are also modified by
      extracellular Mg2+.

PMID- 1361029
TI  - Transglutaminase activity in primary and subcultured rat astroglial cells.
AB  - Transglutaminases, calcium-dependent thiol enzymes, may be involved in cellular
      growth control and differentiation, having an intracellular regulatory role in
      some post-translational modifications found in various classes of proteins. In
      order to elucidate the involvement of this class of enzymes in cellular
      differentiation processes, we have assayed transglutaminase activity in primary
      and subcultured rat glial cells. Reduced activity was found from 3rd to 5th
      passage. In the 5th passage the activity was some 50% of that found in the
      primary cultures and was not restored by addition of 10 microM retinoic acid. The
      decrease of TGase activity, observed during serial passages, could represent an
      early metabolic alteration related to cell dedifferentiation and loss of growth
      control. In fact, the subcultured cells may have undergone a "disarranged" state,
      as confirmed by a decrease in GFAP-stained cells and glutamine synthetase
      activity, respectively, immunocytochemical and biochemical markers of astroglial
      cells.

PMID- 1361030
TI  - NMDA receptor modification in the fetal guinea pig brain during hypoxia.
AB  - The effect of maternal hypoxia on the modification of the fetal brain cell
      membrane N-methyl-D-aspartate (NMDA) receptor and its modulatory sites was
      investigated. Experiments were conducted in pregnant guinea pigs of 60 days of
      gestation. Guinea pig fetuses were exposed to maternal hypoxia (FiO2 = 7%) for 60
      minutes. Tissue hypoxia in the fetal brain was documented biochemically by
      decreased levels of ATP and phosphocreatine (91.3% and 88.6% lower than normoxia,
      respectively). MK-801 binding characteristics (Bmax = number of receptors, Kd =
      affinity of receptor) were used as an index of NMDA receptor modification. P2
      membrane fraction was prepared from the cortex of normoxic and hypoxic fetal
      brain and washed thoroughly before carrying out the binding assay. In hypoxic
      brains, Bmax decreased from the normoxic control level 0.79 +/- 0.03 pmol/mg
      protein to 0.58 +/- 0.03 pmol/mg protein (P < 0.005) and Kd value decreased
      (increased affinity) from 8.54 +/- 0.27 nM to 4.01 +/- 0.23 nM (P < 0.005)
      respectively. The MK-801 binding in the absence of added glutamate and glycine in
      hypoxic brain was 100% higher as compared to controls, indicating an increased
      sensitivity of the NMDA receptor to activation. The spermine dependent maximum
      activation of the NMDA receptor increased to 44% in the hypoxic animals as
      compared to 25% in controls. The Mg2+ response of the NMDA receptor was not
      affected by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361031
TI  - Modification of modulatory sites of NMDA receptor in the fetal guinea pig brain
      during development.
AB  - Ontogeny of the NMDA receptor and modification of its modulatory sites in the
      developing fetus brain was determined. MK-801 binding characteristics in the
      presence of glycine, glutamate, Mg2+ and spermine were determined and used as an
      index of NMDA receptor modification. Experiments were performed on guinea pig
      fetuses at 30, 45, 50, 55, and 60 days (term = 63 days) of gestation. The Bmax
      value increased approximately three-fold from 30 days to 60 days of gestation.
      The Kd value decreased during the 45-50 day period and then increased toward the
      end of gestation. The Bmax value reached its maximum level by 55 days of
      gestation, indicating the presence of a maximum number of NMDA receptors by this
      age, while the apparent affinity of the receptor showed its peak at 45-50 days of
      gestation, indicating a potential role for NMDA receptor during the proliferation
      period of brain development in the guinea pig fetus. The activation of NMDA
      receptor in the presence of glutamate (10 microM) and glycine (10 microM), as
      measured by MK-801 binding, was absent at 30 days gestation, with the earliest
      observation occurring at 35 days gestation. The spermine dependent activation
      decreased with gestational age. Mg2+ ions increased MK-801 binding in the range
      of 1-20 microM concentration. Sensitivity to Mg2+ dependent activation increased
      with the gestational age (from 10 microM Mg2+ at 45 days to 2.5 microM at 55 and
      60 days).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361032
TI  - Effects of alpha 2- and beta-adrenoceptor agonists on growth hormone secretion
      following lesion of the noradrenergic system of the rat.
AB  - The aim of the present investigation was to lesion the noradrenergic system and
      to measure the effect on growth hormone (GH) secretion following peripheral
      administration of alpha 2- and beta-adrenoceptor agonists. Direct injection of
      these agonists into the paraventricular nucleus of the hypothalamus (PVN) and its
      effect on GH secretion were also investigated. Systemic administration of N-2
      chloroethyl-N-ethyl-2-bromobenzylamine (DSP4, 60 mg/kg, injected i.p. 10 days
      prior to experimentation) significantly decreased the noradrenaline (NA) content
      of the hippocampus, frontal cortex and hypothalamus but had no effect on the
      dopamine (DA) or serotonin (5-HT) content of these areas. Bilateral injection of
      6-hydroxydopamine (6-OHDA, 10 micrograms/microliters, 14 days prior to
      experimentation) into the medial forebrain bundle (MFB) caused a greater
      reduction of NA and also decreased the DA and 5-HT content of the hypothalamus.
      Analysis of the PVN of the hypothalami of rats following 6-OHDA lesion of the MFB
      showed significantly decreased NA and 5-HT content. Neither DSP4 treatment nor 6
      OHDA lesion of the MFB affected the clonidine (250 micrograms/kg, i.p.) induced
      stimulation of GH secretion. Injection of isoproterenol (1 mg/kg, i.p.) had
      varying effects on GH secretion. It stimulated GH release in control rats but not
      in DSP4 or MFB lesioned rats. Direct injection of clonidine (0.1
      microgram/microliters) into the PVN significantly stimulated GH secretion,
      whereas injection of isoproterenol (2.5 micrograms/microliters) into the PVN did
      not affect GH levels when compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361035
TI  - [Pain and the immune system. Physiopathologic and clinical correlations].

PMID- 1361034
TI  - A syndrome of autosomal dominant alternating hemiplegia: clinical presentation
      mimicking intractable epilepsy; chromosomal studies; and physiologic
      investigations.
AB  - We report the familial occurrence and apparent autosomal dominant inheritance of
      alternating hemiplegia of childhood. The proband, a 9-year-old boy, presented
      with developmental retardation, rare tonic-clonic seizures, and frequent episodes
      of flaccid alternating hemiplegia that had been presumed to represent postictal
      paralysis. The hemiplegia spells, which started in his first year, did not
      respond to multiple antiepileptics. Between attacks, there was choreoathetosis
      and dystonic posturing. Father, brother, paternal uncle, and paternal grandmother
      had similar histories of alternating hemiplegia. Investigations included negative
      CT, metabolic, and coagulation studies. EEG and SPECT 99mTc exametazime scanning
      failed to reveal any significant slowing or any major changes in cortical
      perfusion during hemiplegia as compared with nonhemiplegic periods. The karyotype
      revealed a balanced reciprocal translocation, 46,XY,t(3;9)(p26;q34) in the
      patient, in all the affected living relatives, and in one apparently unaffected
      sibling. The asymptomatic mother had a normal karyotype. Analysis of DNA markers
      was consistent with the karyotype results. Both affected siblings were treated
      with and responded to flunarizine therapy, with a greater than 70% decrease in
      attack frequency. Documented flunarizine trough serum concentrations were 28.9
      ng/ml in the proband and 6.6 ng/ml in his brother.

PMID- 1361033
TI  - Glutamate-like immunoreactivity in chick cerebellum and optic tectum.
AB  - Glutamate was coupled via glutaraldehyde to bovine serum albumin. The conjugate
      was used for raising specific anti-glutamate antibodies. The purified antibody
      was used for immunostaining of chick cerebellum and optic tectum. Staining was
      intense in the molecular layer and in cell bodies of the granule cell layer. In
      the optic tectum a diffuse staining was detected in the superficial layers of
      stratum griseum fibrosum superficiale and in cell bodies especially in the layers
      a and e. Large cell bodies located in the stratum griseum centrale were also
      stained.

PMID- 1361037
TI  - [Endogenous opioid systems as biochemical basis of pain control].

PMID- 1361036
TI  - [Pharmacophysiology of inotropic agents].

PMID- 1361038
TI  - [Comparative study of 24-hour continuous gastric pH-measurements in healthy
      people and in patients with pancreatic neoplasms treated with duodeno-pancreatic
      head resection].
AB  - The Authors compare pH measurements taken over a 24-h period to monitor, using an
      original method, a sample group of 11 healthy subject and a series of patients
      suffering from gastroenteropancreatic diseases. The data obtained confirm the
      utility of the functional study of gastrointestinal secretion.

PMID- 1361039
TI  - [Somatostatin in the treatment of lymphorrhea after lateral neck dissection].
AB  - A new pharmacological effect of somatostatin has been verified in the treatment
      of lymphorrea due to a thoracic duct injury, produced during left lateral neck
      dissection. The drug (stilamin 3 mcg/kg/h in continuous venous infusion) allowed
      in 3 case a strongly decrease of the lymphatic loss within 24 hours and the
      complete depletion within 6 days. Further studies are required to clarify the
      dynamic effects of the drug in this complication.

PMID- 1361040
TI  - [Therapy of arterial hypertension in diabetic patients. When to start the
      treatment and which drugs to use?].
AB  - In this review, the Authors analyzes the more recent data in the Literature about
      the major cardiovascular risks in diabetic patients affected by systemic arterial
      hypertension. The more effective pharmacological and not pharmacological
      treatment is suggested. Particularly the advantages and more important side
      effects of antihypertensive drugs are emphasized.

PMID- 1361041
TI  - [Empty sella syndrome (ESS) associated with primary hyperparathyroidism. A
      clinical case and review of the literature].
AB  - The report describes a patient with coexisting primary hyperparathyroidism due to
      adenoma of the left superior lobe and the primary empty sella syndrome (ESS).
      Pathogenetic mechanisms, clinical pictures, associated illnesses and similarity
      between these diseases are discussed. A complete diagnostic procedure and follow
      up is necessary even if the illnesses are oligosymptomatic. In fact this
      association may be part of multiple endocrine neoplasia (MEN) or other endocrine
      diseases.

PMID- 1361042
TI  - Simultaneous measurement by HPLC of the excitatory amino acid transmitter
      candidates homocysteate and homocysteine sulphinate supports a predominant
      astrocytic localisation.
AB  - Primary cultures of mouse cerebral cortex neurons, cerebellar granule cells and
      cortical astrocytes were maintained in vitro for respectively 8-10, 7-10 and 21
      24 days. Following these times, amino acids were extracted from the cells by use
      of ice-cold 70% (v/v) ethanol and the extracts lyophilised. The lyophilised
      extracts when resuspended were subjected to reverse-phase high performance liquid
      chromatographic (HPLC) analysis for detection of free amino acids. Samples of
      cell culture growth medium and water blanks were treated in a similar manner.
      Identification of L-homocysteate (HCA) and L-homocysteine sulphinate (HCSA) was
      undertaken by matching retention times with regard to external standards and by
      'spiking' cell extracts with authentic compounds. On this basis, HCA and HCSA
      were consistently detectable in astrocytes at levels of, respectively, 72.3 +/-
      33.7 pmol/mg protein (n = 24) and 49.4 +/- 28.7 pmol/mg protein (n = 24).
      However, in neurons, a peak corresponding to HCSA could not be detected above the
      background noise, while the area of the peak corresponding to HCA was always
      greater than, but not significantly different from, that of the background noise
      present in water blanks. HCA and HCSA were not detectable in the serum used for
      preparation of the cell culture growth medium. Taken together, these findings
      indicate a predominant localisation of HCA and HCSA in astrocytes which, at least
      in culture, appear to possess the metabolic machinery necessary for synthesising
      and storing these amino acids without any neuronal influence.

PMID- 1361043
TI  - Sulmazole effects on PGE2 and D-Ala2-Met-enkephalinamide modulation of cyclic AMP
      synthesis and neurotransmitter release in a sympathetic ganglion.
AB  - In the guinea-pig superior cervical ganglion, the Gi blocking agent sulmazole
      enhanced the basal and prostaglandin E2-induced stimulation of cyclic AMP
      synthesis but had no effect on the prostaglandin-dependent inhibition of
      acetylcholine release. On the contrary sulmazole counteracted the inhibitory
      effect of D-Ala2-Met-enkephalinamide both on cyclic AMP formation and
      acetylcholine release. Moreover sulmazole eliminated the supra-additive effect of
      the combination of prostaglandin + opiate on cyclic AMP synthesis. The presence
      of a Gi-coupled opiate receptor at the pre-and postsynaptic levels is suggested.

PMID- 1361044
TI  - Effects of oxiracetam on neurotransmitter release from rat hippocampus slices and
      synaptosomes.
AB  - The effects of the nootropic drug oxiracetam on the K(+)-evoked overflow of [3H]D
      aspartic acid ([3H]D-ASP), [3H]acetylcholine ([3H]ACh), [3H] gamma-aminobutyric
      acid ([3H]GABA), [3H]noradrenaline ([3H]NA) and [3H]5-hydroxytryptamine ([3H]5
      HT) have been studied in superfused rat hippocampal slices. The overflow of [3H]D
      ASP was enhanced by low concentrations of oxiracetam (0.01-1 microM) but not by
      high concentrations (10-100 microM) which showed some tendency to inhibit it.
      Similarly, low concentrations of oxiracetam increased, although less effectively,
      the depolarization-evoked overflow of [3H]ACh, whereas higher concentrations were
      without effect. At the concentrations active on [3H]D-ASP and [3H]ACh overflow
      oxiracetam did not affect that of [3H]GABA, [3H]NA or [3H]5-HT. The oxiracetam
      effects present in slices could not be observed in hippocampal synaptosomes. Thus
      oxiracetam may selectively increase the release of glutamate and acetylcholine in
      hippocampus by a mechanism which appears not to be sited in the releasing nerve
      terminals.

PMID- 1361045
TI  - Homocysteate and homocysteine sulfinate, excitatory transmitter candidates
      present in rat astroglial cultures.
AB  - The presence of homocysteate and homocysteine sulfinate was demonstrated in
      extracts prepared from cultures of rat cortical and cerebellar astrocytes as well
      as from C6 glioblastoma cells by o-phthalaldehyde derivatization and subsequent
      HPLC analysis. Homocysteate-like immunoreactivity was found in cultured cortical
      astrocytes by postembedding immunocytochemistry at the level of light microscopy.
      These findings support the notion of a glial localization of the excitatory
      transmitter candidate homocysteate.

PMID- 1361046
TI  - Co-localization of Met-enkephalin and somatostatin in the spinal cord of the rat.
AB  - A double-labelling immunofluorescence study of rat spinal dorsal horn was carried
      out with antisera to Met-enkephalin and somatostatin. Varicosities in laminae I
      and II were frequently immunoreactive with both antisera, and in addition some
      neuronal cell bodies in lamina II possessed both types of immunoreactivity. These
      findings suggest that enkephalin and somatostatin coexist in some axons within
      the rat superficial dorsal horn and that at least some of these axons are derived
      from local neurones.

PMID- 1361048
TI  - Recent Advances in Hormonal Therapy in Cancer. Symposium proceedings. Amsterdam,
      The Netherlands, September 15, 1991.

PMID- 1361047
TI  - Cholecystokinin- and dopamine-containing mesencephalic neurons provide distinct
      projections to monkey prefrontal cortex.
AB  - Retrograde transport and immunohistochemical techniques were utilized to
      determine if cholecystokinin (CCK)-containing neurons of the primate ventral
      mesencephalon project to prefrontal cortex, and to examine what relation the CCK
      innervation of prefrontal cortex bears to the dopaminergic projection to this
      region. Following injections of Fast blue into monkey prefrontal cortex,
      retrogradely labeled, CCK-positive neurons were observed predominantly in
      rostromedial portions of the ventral mesencephalon; these CCK-containing
      projection neurons were not immunoreactive for tyrosine hydroxylase. Furthermore,
      dual-labeling studies in the prefrontal cortex revealed that CCK and tyrosine
      hydroxylase were present in separate populations of axons. These results
      demonstrate that the CCK innervation of monkey prefrontal cortex arises from both
      intrinsic and extrinsic sources; in contrast to the rat, the extrinsic CCK
      innervation of monkey prefrontal cortex is distinct from the dopaminergic
      mesocortical projection.

PMID- 1361049
TI  - Immune control of murine coccidiosis: CD4+ and CD8+ T lymphocytes contribute
      differentially in resistance to primary and secondary infections.
AB  - The effect of treatment with monoclonal antibodies (Mabs) which deplete CD4+ or
      CD8+ T lymphocytes, on infections with Eimeria spp. was examined in NIH mice.
      Treatment with anti-CD4 Mab increased susceptibility to primary infections with
      E. vermiformis or E. pragensis and reduced the subsequent resistance of the mice
      to homologous challenge. Similar treatment of immune mice did not affect their
      resistance to re-infection but this was reduced in mice depleted of CD8+ T
      lymphocytes. In mice immunized with E. vermiformis the effect of CD8(+)-depletion
      was very slight, apparent only as the presence of small numbers of oocysts in the
      faeces of some mice; in mice immunized with E. pragensis there was a small,
      though significant, increase in oocyst production, compared with controls and
      anti-CD4-treated groups. These results confirm the importance of mechanisms
      involving the function of CD4+ T lymphocytes in the control of primary infections
      with Eimeria spp. and indicate that CD8+ cells play some part in the expression
      of resistance to reinfection. They also show that a major part of this resistance
      was not affected by either of the treatments given.

PMID- 1361050
TI  - Dynamic interaction between CD4+ T cells and parasitic helminths: mathematical
      models of heterogeneity in outcome.
AB  - Potential mechanisms of immunoregulation have been investigated for the capacity
      to generate heterogeneity in the outcome of infection with helminth parasites. We
      have developed a mathematical model of the interaction between T cell and
      parasite populations, based on the assumption that activation of a Th1 CD4+ T
      cell response is required for host resistance. Antigen dose-dependent inhibition
      of Th1 cell proliferation generates heterogeneity in the outcome of host response
      to infection, with relatively low levels of exposure inducing resistance, and
      high levels of exposure associated with host susceptibility. Heterogeneity is
      additionally predicted in the duration of infection before individuals of the
      resistant class clear infection, with infection becoming more prolonged as the
      level of exposure rises. Similar categories of response are predicted if an
      alternative regulatory mechanism, that of interferon gamma-regulated control of
      Th1 cell differentiation, is substituted into the model. However, the
      relationship between level of exposure and duration of infection is reversed.
      Results are discussed in the context of how these simple models of parasite
      immune system interactions might be used to make predictions concerning specific
      examples of parasitic infection.

PMID- 1361051
TI  - Age-related standards for T lymphocyte subsets based on uninfected children born
      to human immunodeficiency virus 1-infected women. The European Collaborative
      Study.
AB  - The T lymphocyte subsets in the peripheral blood of 459 uninfected children born
      to white human immunodeficiency virus 1-infected women included in the European
      Collaborative Study were measured at regular intervals from birth. More than 2400
      observations were used to create smooth age-related reference ranges for CD4 and
      CD8 counts and percentages, CD4:CD8 ratio and absolute lymphocyte count.
      Standards are presented for children up to 4 years of age. CD4, CD8 and absolute
      lymphocyte count rose after birth, peaked at around 6 to 9 months of age and then
      declined toward adult values. CD4 percentage and CD4:CD8 ratio declined steadily
      from birth onwards. Centile lines for CD4 count and CD4:CD8 ratio converged
      markedly with age. For the CD4 values, only 3 to 5% of the variation was
      attributable to differences between the 10 participating centers. These standards
      allow T lymphocyte abnormalities to be used more effectively as markers for
      disease progression and assist in the clinical follow up of human
      immunodeficiency virus 1-infected children. They also provide a basis for
      initiating antiretroviral treatment or antimicrobial prophylaxis.

PMID- 1361052
TI  - Activation of alpha 1-adrenoceptors modulates the inwardly rectifying potassium
      currents of mammalian atrial myocytes.
AB  - The selective alpha 1-adrenergic agonist methoxamine (10(-4)-10(-3) M), in the
      presence of propranolol (10(-6) M), can reduce both the inwardly rectifying K+
      background current (IK1) and the muscarinic cholinergic receptor-activated K+
      current (IK,ACh) in rabbit atrial myocytes resulting in action potential
      prolongation during the final phase of repolarization and a depolarization of the
      resting membrane potential. The reduction of these K+ currents(s) by alpha 1
      adrenoceptor stimulation was insensitive to pre-treatment of atrial myocytes with
      pertussis toxin (0.15-0.5 micrograms/ml) and was irreversible following
      intracellular dialysis with the non-hydrolysable guanosine triphosphate (GTP)
      analogue, Gpp(NH)p (1-5 x 10(-3) M). Neither the protein kinase C (PKC)
      inhibitors, 1((5-isoquinolinesulphonyl)-2-methylpiperoxine (H-7) (5 x 10(-5) M)
      and staurosporine (1 x 10(-7) M), nor "downregulation" of PKC by prolonged
      phorbol ester exposure (5 x 10(-7) M, for 7-8 h) had an effect on the alpha 1
      adrenergic modulation of this K+ current. Under cell-attached patch-clamp
      conditions, bath application of methoxamine reversibly decreased acetylcholine
      induced single-channel activity, thus confirming the observed reduction of the
      ACh-induced current under whole-cell voltage clamp. These results demonstrate
      that the alpha 1-adrenoceptor, once activated, can reduce current through two
      different inwardly rectifying K+ channels in rabbit atrial myocytes. These
      current changes are mediated via a pertussis toxin-insensitive GTP-binding
      protein, and do not appear to involve the activation of PKC.

PMID- 1361053
TI  - Characterization of cell-surface beta-adrenergic ([3H]CGP-12177) binding in adult
      rat ventricular myocytes: lack of regulation by beta-agonists at physiological
      concentrations.
AB  - The major focus of this paper is the characterization and quantification of rat
      cardiomyocyte, cell-surface beta-adrenergic receptors labelled with the
      hydrophilic radioligand [3H]CGP-12177. The ventricular cardiomyocytes used in
      these experiments have previously been extensively studied in our laboratory and
      confirmed to be functionally compatible with similar cells in vivo. Specific
      binding of [3H]CGP was stereospecific, saturable and of high affinity. Binding of
      [3H]CGP was also readily reversible, demonstrated appropriate drug specificity
      and positively correlated with increasing cell concentrations. The potency of the
      beta 1-antagonist atenolol was almost 100 times higher than that of the beta 2
      antagonist ICI-118.551 in binding to the [3H]CGP binding site. This preparation
      appears ideal for the investigation of beta-adrenergic receptor regulation in
      heart cells. Indeed, our initial experiments show clearly that pharmacological
      concentrations of isoproterenol, and norepinephrine, can reduce (down-regulate)
      the number of specific [3H]CGP binding sites. This result is in agreement with
      many other reports on similar experiments in a variety of cell types. However,
      physiologically relevant concentrations of these two agonists (1-100 nM) do not
      induce down-regulation of the beta-adrenergic receptors in short-term (2 h)
      incubations. Nevertheless, the high-affinity receptors that we have described
      mediate a contractile response to isoproterenol in the nanomolar concentration
      range (EC50 = 3.6 +/- 0.3 nM). This is approximately 300 times lower than the
      concentration needed to produce down-regulation. Thus, our data indicate that
      short-term down-regulation of cardiomyocyte beta-adrenergic receptors can only be
      observed with high, pharmacological concentrations of isoproterenol.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1361054
TI  - [Cryptorchidism].
AB  - Cryptorchidism is a frequent abnormality which affects approximately 1% of
      children at age 1 year. Many nonscrotal testes are retractile and require no
      therapy. The pathogenesis remains controversial and involves possible mechanical,
      dysgenetic or hormonal factors. The latter are consistent with a partial defect
      in the hypothalamo-pituitary-gonadal axis, which may cause progressive histologic
      alterations in the testes after the first 6 months of life. Ultrasound is the
      simplest diagnostic technique (after clinical examination) to identify the testes
      in the inguinal region, while Magnetic Resonance Imaging can be performed to
      visualize abdominal testes. Therapy is still a matter of controversy. Hormonal
      treatments with HCG, LHRH or both should be used as first-intention treatment and
      their efficacy ranges from 0% to 60% in the various studies. LHRH nasal spray
      seems less effective if used alone. An early surgical treatment is recommended if
      the gonad is in the abdomen or close to the internal inguinal ring. The risk of
      cancer is increased in subjects with a history of cryptorchidism and even
      includes the contralateral descended testes. Early orchidopexy is not associated
      with a certain decrease of the risk. Cancer can be prevented by searching for in
      situ carcinoma with a biopsy performed after puberty. Fertility is impaired
      mainly in men with a history of bilateral cryptorchidism. There is weak evidence
      that early orchidopexy may improve fertility rates.

PMID- 1361055
TI  - [Use of polymerase chain reaction (PCR) in clinical diagnosis].

PMID- 1361056
TI  - Cardiovascular research: imaging, diagnosis and therapy. Proceedings of a
      research symposium. Manchester, 2-3 October 1991.

PMID- 1361057
TI  - Postoperative pain relief.

PMID- 1361058
TI  - Phylogenetic relationships of the thylacine (Mammalia: Thylacinidae) among
      dasyuroid marsupials: evidence from cytochrome b DNA sequences.
AB  - DNA sequences from the mitochondrial cytochrome b gene were obtained from a
      museum specimen of the presumed extinct thylacine (Thylacinus cynocephalus) and
      were compared with homologous sequences from 13 representatives of the Australian
      marsupial family Dasyuridae. The relationship of the thylacine to dasyurids has
      been suggested by previous anatomical and molecular studies, but its position
      within the dasyuroid radiation has not been addressed with genetic data.
      Phylogenetic analysis of the sequences reported here suggests that the thylacine
      is a sister group to Dasyuridae and lends support to the hypothesis that
      Thylacinus represents an ancient Australian marsupial lineage. Relationships with
      Dasyuridae support the results of other recent molecular studies, particularly in
      showing the affinities of endemic New Guinean subfamilies with larger Australian
      clades.

PMID- 1361059
TI  - Mechanical filtering of sound in the inner ear.
AB  - We have studied the distortion generated by the cochlea to gain insight into the
      mechanisms responsible for the sharp tuning or 'frequency selectivity' of the
      inner ear. We used two stimulating tones of moderate intensity which are
      progressively separated in frequency, and measured the ear canal cubic distortion
      components which are generated as a consequence of the stimulus interaction in
      the cochlea. We inferred that the distortion is generated from the frequency
      region of the higher of the two stimulus tones and that it is then band-pass
      filtered by a structure which is tuned to a frequency just over half an octave
      below that of the high-frequency tone. We suggest that the structure responsible
      for this band-pass filtering is the tectorial membrane, and we conclude that our
      results support theories of cochlear mechanics in which resonances due to the
      tectorial membrane interact with those of the basilar membrane to enhance the
      frequency selectivity of the inner ear.

PMID- 1361060
TI  - Activation of L-type Ca2+ currents in cardiac myocytes by photoreleased GTP.
AB  - L-type calcium currents (ICa) were recorded from isolated ventricular myocytes by
      using standard patch-clamp methods. In the absence of agonist, photorelease of
      GTP by flash photolysis of intracellularly applied caged-GTP rapidly increased
      the amplitude of ICa over a wide range of membrane potentials. Control
      experiments clearly demonstrated that this effect was not due to either the
      release of photolytic by-products or to the light flash itself. The timecourse
      for activation of ICa by photolysis of caged-GTP was markedly altered by
      intracellular application of either GDP beta S or GTP gamma S. Upon maximal
      stimulation of ICa by intracellular dialysis with cAMP, photoreleased GTP induced
      a small, rapid increase in ICa followed by a gradual inhibition. The presence of
      Rp-cAMPS intracellularly reduced both the magnitude of the response to
      photoreleased GTP and its time to peak. Similar effects were observed when
      protein kinase inhibitor dialysed the cell interior, suggesting that both cAMP
      dependent and independent processes were involved in this effect. We conclude
      that rapid release of GTP within ventricular myocytes, in the absence of agonist,
      causes rapid activation of L-type Ca2+ current. Mechanisms underlying this effect
      include stimulation of adenylate cyclase, together with other, as yet
      uncharacterized, GTP-dependent pathways for increasing ICa in the heart.

PMID- 1361061
TI  - A latitudinal cline in a Drosophila clock gene.
AB  - The clock gene period determines biological rhythmicity in Drosophila
      melanogaster and encodes a protein characterized by an alternating series of
      threonine-glycine pairs. The minisatellite region encoding the threonine-glycine
      repeat is polymorphic in length in natural Drosophila melanogaster populations.
      In this paper we report the geographical analysis of this polymorphism within
      Europe and North Africa. A robust clinal pattern is observed along a north-south
      axis. We suggest the possibility that the length polymorphism could be maintained
      by thermal selection because the threonine-glycine region has been shown to
      provide thermostability to the circadian phenotype.

PMID- 1361062
TI  - Role of the phosphoenolpyruvate-dependent fructose phosphotransferase system in
      the utilization of mannose by Escherichia coli.
AB  - Mutants of Escherichia coli devoid of the membrane-spanning proteins PtsG and
      PtsMP, which are components of the phosphoenolpyruvate-dependent
      phosphotransferase system (PTS) and which normally effect the transport into the
      cells of glucose and mannose, do not grow upon or take up either sugar.
      Pseudorevertants are described that take up, and grow upon, mannose at rates
      strongly dependent on the mannose concentration in the medium (apparent Km > 5
      mM); such mutants do not grow upon glucose but are derepressed for the components
      of the fructose operon. Evidence is presented that mannose is now taken up via
      the fructose-PTS to form mannose 6-phosphate, which is further utilized for
      growth via fructose 6-phosphate and fructose 1,6-bisphosphate.

PMID- 1361063
TI  - Structural and functional evidence for activation of a chick retinoid X receptor
      by eicosanoids.
AB  - The retinoid X receptors (RXR-alpha, RXR-beta and RXR-gamma) are members of the
      steroid-thyroid hormone receptor superfamily of ligand-dependent transcription
      factors. They appear to function as auxiliary proteins that regulate high
      affinity DNA binding and enhance transcriptional activity through heterodimer
      formation with other members of the superfamily. The RXR-alpha, RXR-beta and RXR
      gamma proteins bind and are activated by the naturally occurring retinoid, 9-cis
      retinoic acid. Structural similarities are apparent between retinoic acid and
      various eicosanoids, raising the possibility that eicosanoids may also activate
      retinoid receptors in vivo. We present evidence that lipoxygenase metabolites of
      arachidonic acid at submicromolar concentrations are capable of activating RXR
      gamma activity in transient transfection assays. In addition, molecular modelling
      predicts conformational similarities between some lipoxygenase products and
      retinoic acid. Consistent with this, hydroxyeicosatetraenoic acids are known to
      mimic some actions of retinoids in cell-based assays. These observations raise
      the possibility that eicosanoids, already known to act both as local hormones and
      as intracellular second messengers, may also have a direct role in
      transcriptional activation via nuclear receptors.

PMID- 1361064
TI  - The dependence of calcium-activated potassium currents on membrane potential.
AB  - Previous experiments on cholinergic synapses in chick cochlear hair cells have
      shown that calcium entering through acetylcholine-activated synaptic channels in
      turn activates calcium-dependent potassium currents, resulting in synaptic
      inhibition. In voltage-clamp experiments such currents would be expected to
      increase with depolarization (as the driving force for potassium entry is
      increased) and then decrease towards zero as the membrane approaches the calcium
      equilibrium potential (when calcium entry is suppressed). In the hair cells,
      however, such currents approached zero at about +20 mV, more than 170 mV negative
      to the calcium equilibrium potential. Another feature of the synapse is its post
      junctional morphology: a uniform 20 nm cleft is formed between the postsynaptic
      membrane and the outermost membrane of an underlying cisterna. Here we present a
      model in which synaptic activation results in calcium influx into the subsynaptic
      cleft and thence into the bulk of the cytoplasm. The model suggests that the
      voltage dependence of the calcium-activated potassium current can be accounted
      for by only two basic assumptions: (i) entry of calcium through the activated
      synaptic channels by simple diffusion; and (ii) activation of the potassium
      channels by the cooperative action of four calcium ions. In addition, the model
      suggests that during activation the calcium concentration in the restricted
      subsynaptic space can reach levels adequate to activate the potassium channels,
      without requiring additional, more complicated, considerations (for example,
      secondary calcium release from the cisterna).

PMID- 1361065
TI  - Coloured noise or low-dimensional chaos?
AB  - Devising a method capable of distinguishing a low-dimensional chaotic signal that
      might be embedded in a noisy stochastic process has become a major challenge for
      those involved in time-series analysis. Here a null hypothesis approach is used
      in conjunction with a known nonlinear predictive test, to probe for the presence
      of chaos in epidemiological data. A probabilistic set of rules is used to
      stimulate a historic record of New York City measles outbreaks, generally
      understood to be governed by a chaotic attractor. The simulated runs of
      'surrogate data' are carefully constructed so as to be free from any underlying
      low-dimensional chaotic process. They therefore serve as a useful null model
      against which to test the observed time series. However, despite the assumed
      differences between the dynamics of measles outbreaks and the null model, a
      nonlinear predictive scheme is found to be unable to differentiate between their
      characteristic time series. The methodology confirms that, if there is in fact a
      chaotic signal in the measles data, it is extremely difficult to detect in time
      series of such limited length. The results have general relevance to the analysis
      of physical, ecological and environmental time series.

PMID- 1361066
TI  - Growth Factors in Early Embryonic Development. ASRB-Serono Satellite Symposium.
      Australia, 3 October 1991.

PMID- 1361067
TI  - International meeting on Molecular Approaches to Nephrology: Prospects in
      Diagnosis and Management. Bari, Italy, March 19-21, 1992. Abstracts.

PMID- 1361068
TI  - Inhaled salmeterol in the treatment of patients with moderate to severe
      reversible obstructive airways disease--a 3-month comparison of the efficacy and
      safety of twice-daily salmeterol (100 micrograms) with salmeterol (50
      micrograms).
AB  - Three-hundred and fifty patients with moderate to severe reversible obstructive
      airways disease (forced expiratory volume in 1 s or peak expiratory flow rate <
      or = 50% predicted, a 15% reversibility to inhaled salbutamol and symptomatic)
      were recruited into a multi-centre, multinational, double-blind, parallel-group
      randomized study. Two-hundred and eighty-three patients were randomized to
      receive 50 micrograms salmeterol twice daily or 100 micrograms salmeterol twice
      daily administered from a metered-dose inhaler for 3 months. Salbutamol (100
      micrograms per metered actuation) was provided for symptomatic relief. Morning
      and evening peak expiratory flow rate (PEFR), day-time and night-time asthma
      symptoms and additional bronchodilator usage were recorded by the patient on a
      daily basis. Lung function and patient/physician assessment of treatment efficacy
      were recorded at scheduled clinic visits. Safety was determined by monitoring
      adverse events and standard biochemical, haematological and cardiovascular
      parameters. Salmeterol 100 micrograms twice daily was consistently superior to
      salmeterol 50 micrograms twice daily in morning and evening PEFR measurements
      (mean differences between the treatments: 10-14 l min-1 for morning, 95% CI-0, 22
      l min-1, P = 0.047; and 10-15 l min-1 for evening, 95% CI 2, 22 l min-1, P =
      0.023). The improvement in PEFR was independent of concurrent steroid usage, with
      the most marked improvement being seen in the more severe asthmatics requiring
      concurrent oral corticosteroids (mean differences between the treatments: 27-31 l
      min-1, 95% CI: 3,55 l m-1, P = 0.027).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361069
TI  - The relationship of putrescine incorporation to transferrin uptake by
      reticulocytes.
AB  - We previously reported that putrescine incorporation occurred during transferrin
      uptake by rat reticulocytes (1). Both the putrescine incorporation and
      transferrin uptake were enhanced by the presence of Ca2+ and A23187. Furthermore,
      putrescine dose-dependently increased the transferrin uptake. Additionally,
      transglutaminase inhibitors partially blocked not only the putrescine
      incorporation but also the transferrin uptake.

PMID- 1361070
TI  - Effect of aspirin on vascular tone and reactivity to vasoactive amines in the dog
      lung.
AB  - The effect of increasing blood levels of aspirin on pulmonary hemodynamics and
      pressor response to vasoactive amines was examined in the isolated canine lung
      lobe, blood perfused at constant flow. At steady state lobar vascular resistance
      (LVR), lobes were challenged with either 250 micrograms serotonin (5-HT; n = 4),
      5.0 mumol acetylcholine (ACh; n = 4) or 50 micrograms norepinephrine (NE; n = 4)
      before and after blood aspirin concentration [ASA] was incrementally increased
      from 17 to 3140 microM. LVR was partitioned into arterial (Ra) and venous (Rv)
      segments by venous outflow occlusions 20 min after each ASA addition and at the
      peak of the pressor response to each amine. ASA treatment was associated with a
      dose-related 105% increase in LVR (P < 0.01) accounted for by a 154% increase in
      Ra (P < 0.01) and a 70% increase in Rv (P < 0.01) at 3150 microM ASA (n = 12). In
      spite of increased vascular tone, higher [ASA] also potentiated increases in both
      pulmonary arterial pressure and LVR to both 5-HT and NE whereas only Ra increased
      with ACh challenge. Thus, the increase in pulmonary vascular tone and reactivity
      to vasoactive amines is positively correlated with blood aspirin levels in the
      dog.

PMID- 1361071
TI  - The Biotherapy of Cancer-VI. Proceedings of a symposium. San Diego, California,
      May 15, 1992.

PMID- 1361072
TI  - [Anti-neutrophil cytoplasmic antibodies (ANCA): major progress in the diagnosis
      of vasculitis].
AB  - ANCA antibodies represent a family of autoantibodies directed against neutrophil
      enzymes. Immunofluorescence patterns allow to distinguish c-ANCAs from p-ANCAs.
      The detection of ANCAs is often a key element for the diagnosis of Wegener's
      granulomatosis, microperiarteritis, Churg-Strauss syndrome and idiopathic rapidly
      progressive glomerulonephritis. Although the pathogenic role of ANCAs is not
      firmly established, their detection often allows an early therapeutic decision in
      necrotizing vasculitides.

PMID- 1361073
TI  - [Non-atheromatous angiopathies].

PMID- 1361074
TI  - AIDS and Trojan horses.

PMID- 1361075
TI  - Primary stimulation of CD4+ cells in the presence of IL-4 or IFN-gamma alters the
      frequencies of cytokine-producing cells at restimulation.
AB  - The induction of specific effector functions in naive T cells may be directed by
      accessory signals during activation. These could be elicited through binding to
      cell surface molecules or through factors secreted by antigen-presenting cells or
      other simultaneously activated cells. We have investigated the influence of CD8+
      cells and of exogenously added cytokines (interleukin (IL)-2, IL-4 and interferon
      (IFN)-gamma) on the cytokine production in splenic CD4+ T cells. IL-2, IL-4, IL-5
      and IFN-gamma production in CD4+ cells was measured at the single cell level
      during primary mitogen stimulation in vitro in the presence or absence of factors
      or CD8+ cells. On day 5 the cells were restimulated with mitogen alone and
      analysed to evaluate the short-term development of cytokine-producing cells in
      such cultures. Preactivation in the presence of either exogenous IL-4 or IFN
      gamma led to an increased production of IL-4 and IFN-gamma respectively at
      restimulation, and the effects of both IL-4 and IFN-gamma were augmented by IL-2.
      After preactivation in the presence of IL-2 and IL-4, every third CD4+ cell could
      be induced to produce IL-4. Exogenous IL-4 or IFN-gamma further decreased each
      other's production. Depletion of CD8+ cells before activation resulted in a
      slight increase of IL-4-producing cells, indicating that simultaneous activation
      of CD8+ cells will influence lymphokine production in CD4+ cells. The results
      suggest that the pattern of lymphokines induced in naive cells may be influenced
      by factors secreted by preactivated CD4+ and CD8+ cells, and that naive cells are
      preferentially 'recruited' to produce similar cytokines.

PMID- 1361076
TI  - Tumour necrosis factor-beta gene RFLP alleles in Finnish IDDM haplotypes. The
      Childhood Diabetes in Finland (DiMe) Study Group.
AB  - The genes located between class II and class I HLA genes including polymorphic
      tumour necrosis factor (TNF) genes may contribute to the disease susceptibility
      in IDDM. Restriction fragment polymorphisms of the TNF-beta gene have been found
      to be fixed in the major IDDM susceptibility haplotypes, the B62,DR4 haplotype
      being associated with the 10.5-kb fragment and the B8,DR3 haplotype with a 5.5-kb
      fragment. We studied this TNF polymorphism in a sample of diabetic families. In
      all IDDM-associated haplotypes (n = 129) the 5.5-kb allele was more frequent than
      in haplotypes found only in healthy family members (n = 112) (58.1% versus 40.2%,
      P < 0.01). Among IDDM haplotypes the B62,DR4 haplotype was characterized by the
      10.5-kb TNF fragment, whereas two other common Finnish IDDM-associated DR4
      haplotypes--A24,B39,DR4 and A2,B56,DR4--had the 5.5-kb TNF fragment. Both IDDM
      associated and non-associated DR3 positive haplotypes were linked to the 5.5-kb
      fragment. The distribution of various combinations of TNF alleles in IDDM
      probands (n = 63) did not differ from that expected according to the Hardy
      Weinberg distribution. Our results indicate that the 10.5-kb allele of TNF-beta
      gene as such is not a risk factor contributing to DR4/DQ8-associated
      susceptibility. Alternatively, there may be heterogeneity in pathogenetic
      effector mechanisms.

PMID- 1361077
TI  - Adhesion of subsets of human blood mononuclear cells to endothelial cells in
      vitro, as quantified by flow cytometry.
AB  - Binding of leucocytes to endothelial cells (EC) is essential as an initial step
      in inflammatory responses. We present a rapid, non-radioactive method to measure
      adhesion of human lymphoid cells to EC using flow cytometry. Freshly isolated
      peripheral blood mononuclear cells (PBMC) were allowed to adhere to EC grown in
      24-well plates. Non-adhering cells were removed, after which adhering cells and
      EC were dissociated using trypsin/EDTA. These samples were subsequently analysed
      by flow cytometry, using scatter properties to distinguish between adhering cells
      and EC. The ratio of the number of adhering leucocytes and EC was calculated to
      quantify adhesion. Results of the flow cytometric adhesion assay were comparable
      to those obtained with a conventional adhesion assay using chromium-labelled
      cells. We additionally show that by using the flow cytometric adhesion assay,
      adhesion of lymphocytes and monocytes present within the adhering PBMC can be
      quantified simultaneously. As a model, the contribution of LFA-1 (CD11a/CD18) and
      ICAM-1 (CD54) in adhesion of PBMC to EC was studied. It was found that adhesion
      of lymphocytes and monocytes is regulated differently by phorbol ester and that
      the relative contribution of LFA-1 and ICAM-1 differs for both cell types.

PMID- 1361078
TI  - Oligoclonal T cells in rheumatoid arthritis: identification strategy and
      molecular characterization of a clonal T-cell receptor.
AB  - Immunodominant antigens in rheumatoid arthritis (RA) should induce an expansion
      of T cells bearing a corresponding T-cell receptor (TCR). We therefore analysed
      the TCR repertoire at the site of inflammation using two fundamentally different
      strategies. The total TCR repertoire was examined by generating 'representative'
      T-cell clone panels, which were subsequently tested for clonality by restriction
      mapping of the TCR beta gene locus. No clonality was detected in large T-cell
      clone panels generated with cells from three patients. However, when we
      selectively analysed the TCR repertoire of in vivo pre-activated, interleukin-2
      (IL-2)-responsive T cells, significant T-cell/TCR clonality was found in 2 out of
      4 patients. The clonal T cells represented a minority of the total T-cell
      population with an estimated frequency of 1 in 300 to 1 in 1000 cells. Molecular
      characterization of a clonal TCR and the use of a specific TCR V beta MoAb ruled
      out an over-representation of T cells bearing the same V beta element in the
      total T-cell population, rendering the involvement of super-antigens in the
      induction of T-cell clonality in this case unlikely.

PMID- 1361079
TI  - Taxol: the first of the taxanes, an important new class of antitumor agents.
AB  - The taxanes represent the first class of antimicrotubule agents with a new
      mechanism of cytotoxic action since the introduction of the vinca alkaloids
      several decades ago. These compounds may prove to be the "anticancer drugs of the
      1990s," just as the anthracyclines and the platinum compounds were the
      "anticancer drugs" of the 1970s and 1980s. Like the platinums, taxol, the
      prototypic taxane, has shown significant antineoplastic activity in patients with
      advanced ovarian cancer, with response rates ranging from 20% to 50%. Moreover,
      taxol has been shown to be useful in patients with platinum-resistant ovarian
      cancer. Although phase II screening is not yet complete, the results of phase II
      studies of taxol in advanced cancers of the ovary, breast (response rates, 56% to
      62%), and lung (response rates, 21% to 24%) have rekindled interest in the
      microtubule as a prime strategic target for cancer therapy. After briefly
      reviewing the mechanisms of antineoplastic action and resistance and the results
      of preliminary clinical and pharmacological studies, this review will discuss
      several critical issues that will be addressed in future clinical trials,
      developmental directions, and drug supply. Although this review will focus
      primarily on taxol, the results of preliminary investigations with the
      semisynthetic taxane analog taxotere will also be discussed.

PMID- 1361080
TI  - New antimetabolites in the treatment of human malignancies.
AB  - Several new antimetabolites have been evaluated in clinical trials in recent
      years. Those with the most promising activity include the structurally related
      purine analogs fludarabine, 2-chlorodeoxyadenosine, and 2'-deoxycoformycin. These
      compounds have shown impressive activity against a broad spectrum of indolent
      lymphoproliferative disorders, including hairy-cell leukemia, chronic lymphocytic
      leukemia, and low-grade non-Hodgkin's lymphomas. They may also be useful in the
      treatment of acute leukemias. In contrast, they lack activity against common
      solid tumors. They have been generally well tolerated in large clinical trials;
      however, each of them is myelosuppressive and immunosuppressive. It is unlikely
      that any one of these drugs, when used as a single agent, will provide optimal
      therapy for any disease other than, possibly, hairy-cell leukemia. Combinations
      with other cytotoxic agents and biologics are in development, and perhaps they
      will lead to more effective regimens in the future.

PMID- 1361081
TI  - Use of haloperidol decanoate in psychiatric diseases.
AB  - Observations with slow-release neuroleptics used in the treatment of inpatients
      of a psychiatric ward of a general hospital have been discussed. The comparative
      examinations were performed within a period of two and a half years in a total of
      48 patients who were ranged into two groups at random. One group received
      Piportil, the other Haloperidol decanoate therapy. It has to be emphasized that
      Haloperidol is available also in its tablet form and as short-acting injection,
      and is readily accessible (contrary to other products), so it is a good basis for
      assessing the expectable effectivity of and tolerance to depot products. When
      comparing the two drugs, in the course of Piportil administration neuroleptic
      depression developed more frequently, in one case delirium occurred which
      unwanted effects did not develop in the course of the administration of
      Haloperidol decanoate. According to our observations on a low number of cases
      relapse also occurred more frequently in the Piportil-treated cases. Pathological
      change was not observed in the results of routine laboratory examinations in the
      course of the administration of any of the drugs. The advantages of the use of
      depot products have been discussed in detail from both the physician's and the
      patient's aspect. Due to their beneficial antipsychotic action schizophrenic
      clinical conditions and especially paranoid conditions constitute the major
      indication field of these drugs. The use of depot products in the treatment of
      patients refusing therapy means a dramatic change.

PMID- 1361082
TI  - Age-related polymorphism of thymus subpopulations in inbred mice.
AB  - There are striking age-related changes in the demography of thymus lymphocytes,
      i.e. in thymus-cell subpopulations of BALB/c and SJL mice; these changes occur in
      the proportion of cells, identified by various markers, and by the membrane
      density of these markers. The thymuses of both strains undergo an age-related
      increase in the proportion of CD4+ CD8- cells and decrease in CD4+ CD8+ cells.
      Age-related changes in cells that are Pgp-1+ also show marked strain differences:
      Pgp-1+ cells increase in SJL, but not in BALB/c thymuses. In both strains, cells
      with high density of Pgp-1 appear in later life, though this is more marked in
      the thymus of SJL, which also shows a higher relative density at an advanced age,
      than do BALB/c mice. Furthermore, the per cent of cells with high density of Pgp
      1 is larger in thymuses of SJL than in BALB/c mice. The percentage of CD45+
      thymocytes remains unchanged, as animals age. Thymocyte-membrane densities of CD
      45 undergo age-related increases in both SJL and BALB/c. The per cent of cells
      with high density of CD-45 is similar in both strains. Individual variations in
      relative size of subpopulations in SJL mice of the same age are greater in old
      than in young mice; this increase in heterogeneity is manifested by increase in
      standard deviation. Corresponding significant changes have not been observed in
      BALB/c or C57BL/6 mice. Thus, we have detected an intrastrain variation which may
      reflect age-related effects of the impact of stochastic events.

PMID- 1361083
TI  - [Bronchial asthma treated with long-acting beta 2 agonist. Comparison between
      formoterol (12 mu/g) inhaled twice daily and salbutamol (200 mu/g) inhaled 4
      times daily].
AB  - Forty patients with stable asthma and daily need for inhaled beta 2-agonist, were
      included in a randomized double-blind study. They were treated for six weeks with
      inhaled beta 2-agonist, either salbutamol, 4 x 200 micrograms daily, of
      formoterol, 2 x 12 micrograms and 2 x placebo daily. This was preceded by a run
      in period, where all patients received terbutalin-inhalation, 4 x 500 micrograms
      daily. Twenty patients were given formoterol and 18 salbutamol. One patient in
      the salbutamol-treated group discontinued treatment after three weeks, because of
      deterioration of asthma. On a diary card, patients recorded peak expiratory flow
      rate (PEFR) morning and evening before medication, score of asthma symptoms
      (scale 0-3; 0 = no symptoms, and 3 = severe symptoms) and use of additional doses
      of beta 2-agonist. Forced expiratory volume in 1 sec. (FEV1), forced vital
      capacity (FVC) and PEFR were obtained after 0, three and six weeks of treatment.
      Blinded global assessment of the treatment was performed by both patient and
      physician at the end of the study. During run-in the two groups of patients were
      different. The group subsequently treated with salbutamol had a statistical
      significant (ss) higher morning-PEFR, ss fewer asthma-symptom scores than one
      during night and ss less need for additional puffs of beta 2-agonist. During
      treatment, the formoterol-treated group showed an ss increase in morning-PEFR, as
      compared to run-in. Furthermore this group had ss fewer nocturnal symptom scores
      than one and ss less need for extra beta 2-agonist during night, than the
      salbutamol-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361085
TI  - IX Congress of the European Society for Urological Oncology and Endocrinology
      (ESUOE). Trento, Italy, October 29-31, 1992. Abstracts.

PMID- 1361084
TI  - Inhibition of two-step urinary bladder carcinogenesis by the somatostatin
      analogue RC-160.
AB  - Fisher 344 female rats were exposed for 4 weeks to the initiator carcinogen N
      butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) 0.05% in the drinking water and
      thereafter to the promoter carcinogen mitomycin C (0.08 mg per animal per week)
      intravesically for 12 weeks. High incidence of urinary bladder transitional cell
      cancers was observed (17 in situ and 17 invasive carcinomas among 40 rats). When
      the somatostatin analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) was
      administered s.c. at the dose of 50 micrograms per animal per day during 6-week
      period of promotion with mitomycin C, the incidence of urinary bladder cancer was
      dramatically reduced. Only 1 in situ carcinoma was observed among 20 rats and
      only preblastomatous lesions (dysplasias and papillomas) occurred. This effect
      could indicate that RC-160 interferes with the process of promotion by induction
      of enhanced apoptosis (programmed cell death) of the dysplastic urothelial cells.
      RC-160 could be tried therapeutically for the hormonal prevention of malignant
      transformation of preneoplastic lesions in the urinary bladder.

PMID- 1361086
TI  - [Laparoscopic diagnosis and therapy of cryptorchism].
AB  - Between May 1987 and December 1991, laparoscopy was performed in 33 selected
      children with 40 nonpalpable testes, to localize the testes. Of 40 testes sought,
      16 were present (14 intra-abdominal and 2 inguinal), and in 24 cases testicular
      aplasia was verified. The authors describe the technique of laparoscopy for
      unilateral and bilateral undescended testes. Exact anatomical localization of the
      testes by laparoscopy facilitated accurate planning of operative repair. The
      advantages of laparoscopy compared with ultrasound and MR imaging in 14 selected
      patients are described. In 3 patients with an intra-abdominal hypoplastic testis
      we performed laparoscopic orchiectomy. This new operative procedure is described.
      Laparoscopic orchiectomy is minimally invasive, offering a practicable
      alternative to orchiectomy in the case of an atrophic or hypoplastic abdominal
      testis. No complications were noted.

PMID- 1361087
TI  - HIV-negative AIDS cases being studied.

PMID- 1361088
TI  - [Increase in the number of operations for undescended testis].
AB  - In recent years the frequency of operations for cryptorchism has been increasing,
      as evidence by operation protocols of boys qualified for treatment and operated
      on by the same surgeon in certain years. The principles of qualification for
      surgical treatment was evaluated on the basis of testicle position during and
      after the operation, testicle size, presence of inguinal hernia sac or patent
      vaginal peritoneal processes. It was found that the increase in the number of
      these operations in the hospital was not due to changes of these principles.
      Possible causes of increased frequency of these operations are discussed.

PMID- 1361089
TI  - [Treatment of autoimmune diseases and graft rejection with anti-CD4 antibodies].
AB  - Based on the experience that T helper lymphocytes play an important part in the
      initiation and maintenance of various autoimmune diseases and also in graft
      rejection, novel therapeutic approaches have been developed and are under
      investigation. They are aimed at selective inhibition of T cells whose activation
      is unwanted. Useful tools for this purpose are monoclonal antibodies to cell
      surface molecules which are restricted to certain cell populations. In this
      review the concept of treatment with antibodies to CD4-a surface molecule
      characteristic of T helper lymphocytes-is discussed. Encouraged by experimental
      experiences obtained during the past years, a series of case reports were
      published and clinical pilot studies have been performed, the preliminary results
      of which are now becoming available. Anti-CD4 therapy appears to be a promising
      approach. Short-lasting effects can be separated from long-lived effects. The
      latter are not easy to explain, although hypotheses have been developed still
      requiring more detailed experimental confirmation.

PMID- 1361090
TI  - [Prevention and treatment of digestive hemorrhage due to ruptured esophageal
      varices in patients with cirrhosis].
AB  - 1) Emergency treatment. The best treatment remains endoscopic sclerotherapy,
      which controls the bleeding in 90% of the cases. Pharmacologic management stops
      the variceal hemorrhage in 80% of the cases and is indicated before endoscopic
      treatment can be performed. Intravenous somatostatin administration may be
      prolonged for 5 days, even more, and may thus prevent early rebleeding, which is
      not achieved neither by vasopressin nor by glypressin, which administration is
      restricted to 24 hours. Esophageal tamponade is useful to arrest a massive
      variceal bleeding, if vasoactive drugs are not available or not efficient, before
      endoscopic management. If the bleeding persists after 2 sclerotherapy sessions,
      an alternative treatment is mandatory: the patient should be sent to the surgeon
      for a portosystemic shunt if the operative risk is acceptable (child A and B) or
      should become a candidate for a transjugular intrahepatic stent shunt, especially
      if transplantation is considered afterwards. 2) Prevention of recurrent
      hemorrhage. A) Early (within 5 days after the initial bleeding). Somatostatin
      probably prevents early rebleeding, as do sclerotherapy. B) Late. B blockade (+
      nitrates) or long-term sclerotherapy have the same efficacy. Their association
      may improve their results. 3) Prevention of the first bleeding episode.
      Propranolol decrease the risk of variceal rupture from 20% to 9% during the first
      year after the diagnosis of esophageal varices and is the only treatment which
      may be proposed to cirrhotics who did not yet bled form their varices.

PMID- 1361091
TI  - Resistance of hippocampal CA-1 noradrenergic fibers to five minutes of transient
      cerebral ischemia in the gerbil.
AB  - We examined changes in the tyrosine hydroxylase (TH)-immunoreactive fibers
      following 5 min of cerebral ischemia in gerbils using an immunohistochemical
      method 1, 3 and 30 days after ischemia. Almost all CA-1 pyramidal neurons were
      lost 3 days after ischemia, whereas noradrenergic fibers were maintained 30 days
      after ischemia. The present study demonstrated that TH-immunoreactive fibers and
      cells were resistant to transient ischemia, and that there was no sprouting or
      hyperactivity in noradrenergic systems after ischemia.

PMID- 1361092
TI  - [Leydig cell tumor in a patient with type I multiple endocrine neoplasm: study of
      a case and review of the literature].
AB  - Presentation of the case of a 42-year old male patient with Type I Multiple
      Endocrine Neoplasia, known as the Wermer Syndrome, who developed Leydig's cells
      tumour. No association was found between both processes and therefore a
      fortuitus, though worthwhile mentioning given the characteristics and hormonal
      implications of both pathologies, can be presumed.

PMID- 1361093
TI  - Recent progress on kinins. Pharmacological and clinical aspects of the kallikrein
      kinin system. Proceedings of the International Conference "Kinin 91 Munich".
      Munich, September 8-14, 1991.

PMID- 1361094
TI  - Proline-specific aminopeptidases: potential role in bradykinin degradation.
AB  - The N-terminus of bradykinin is shown to be sequentially degraded by the human
      proline-specific aminopeptidases aminopeptidase P (EC 3.4.11.9) and dipeptidyl
      peptidase IV (EC 3.4.14.5). Additional evidence is provided for the hypothesis
      that these proline-specific aminopeptidases play an essential role in the
      degradation of peptides containing an N-terminal Xaa-Pro sequence.

PMID- 1361095
TI  - Recent Progress on Kinins. Pharmacological and clinical aspects of the kallikrein
      kinin system. Part II. Proceedings of the International Conference "Kinin 91
      Munich". Munich, September 8-14, 1991.

PMID- 1361096
TI  - Interactions of T-kinin (Ile-Ser-bradykinin) with neurogenic, autacoidal and
      effector systems in affecting cardiovascular function.

PMID- 1361097
TI  - [Treatment concept of facial pain].
AB  - The therapy of chronic facial pain still poses an important challenge. A
      therapeutical scheme in four steps has been developed. This scheme enables
      modification of the pain therapy depending on localisation, intensity and former
      treatment. It consists of the following steps: 1. Transcutaneous electrical nerve
      stimulation. 2. Medication 3. Extracranial glycerol blocking of the trigeminal
      nerve 4. Neurosurgical treatment with thermocoagulation, chemical glycerol
      rhizotomy and microsurgical decompression. The different therapeutical steps have
      no influence on each other.

PMID- 1361098
TI  - Ambulatory blood pressure and postprandial hypotension.

PMID- 1361099
TI  - A new mtDNA mutation in the tRNA(Lys) gene associated with myoclonic epilepsy and
      ragged-red fibers (MERRF).
AB  - Myoclonic epilepsy with ragged-red fibers (MERRF) has been associated with an A-
      G transition at mtDNA nt 8344, within a conserved region of the tRNA(Lys) gene.
      Although the 8344 mutation is highly prevalent in patients with MERRF, it is not
      observed in 10%-20% of the cases, suggesting genetic heterogeneity. We have
      sequenced the tRNA(Lys) gene of five MERRF patients lacking the common 8344
      mutation. One of these showed a novel T-->C transition at nucleotide position
      8356, disrupting a highly conserved base pair in the T psi C stem. The mutant
      mtDNA population was essentially homoplasmic in muscle but was heteroplasmic in
      blood (47%). Neither 20 patients with other mitochondrial diseases nor 25
      controls carried this mutation. These findings suggest that tRNA(Lys) alterations
      may play a specific role in the pathogenesis of MERRF syndrome.

PMID- 1361101
TI  - Cleft lip with or without cleft palate: associations with transforming growth
      factor alpha and retinoic acid receptor loci.
AB  - The first association study of cleft lip with or without cleft palate (CL/P),
      with candidate genes, found an association with the transforming growth-factor
      alpha (TGFA) locus. This finding has since been replicated, in whole or in part,
      in three independent studies. Here we extend our original analysis of the TGFA
      TaqI RFLP to two other TGFA RFLPs and seven other RFLPs at five candidate genes
      in 117 nonsyndromic cases of CL/P and 113 controls. The other candidate genes
      were the retinoic acid receptor (RARA), the bcl-2 oncogene, and the homeobox
      genes 2F, 2G, and EN2. Significant associations with the TGFA TaqI and BamHI
      RFLPs were confirmed, although associations of clefting with previously reported
      haplotypes did not reach significance. Of particular interest, in view of the
      known teratogenic role of retinoic acid, was a significant association with the
      RARA PstI RFLP (P = .016; not corrected for multiple testing). The effect on risk
      of the A2 allele appears to be additive, and although the A2A2 homozygote only
      has an odds ratio of about 2 and recurrence risk to first-degree relatives
      (lambda 1) of 1.06, because it is so common it may account for as much as a third
      of the attributable risk of clefting. There is no evidence of interaction between
      the TGFA and RARA polymorphisms on risk, and jointly they appear to account for
      almost half the attributable risk of clefting.

PMID- 1361100
TI  - Multiple origins for phenylketonuria in Europe.
AB  - Phenylketonuria (PKU), a disorder of amino acid metabolism prevalent among
      Caucasians and other ethnic groups, is caused primarily by a deficiency of the
      hepatic enzyme phenylalanine hydroxylase (PAH). PKU is a highly heterogeneous
      disorder, with more than 60 molecular lesions identified in the PAH gene. The
      haplotype associations, relative frequencies, and distributions of five prevalent
      PAH mutations (R158Q, R261Q, IVS10nt546, R408W, and IVS12n1) were established in
      a comprehensive European sample population and subsequently were examined to
      determine the potential roles of several genetic mechanisms in explaining the
      present distribution of the major PKU alleles. Each of these five mutations was
      strongly associated with only one of the more than 70 chromosomal haplotypes
      defined by eight RFLPs in or near the PAH gene. These findings suggest that each
      of these mutations arose through a single founding event that occurred within
      time periods ranging from several hundred to several thousand years ago. From the
      significant differences observed in the relative frequencies and distributions of
      these five alleles throughout Europe, four of these putative founding events
      could be localized to specific ethnic subgroups. Together, these data suggest
      that there were multiple, geographically and ethnically distinct origins for PKU
      within the European population.

PMID- 1361103
TI  - Updated listing of haplotypes at the human phenylalanine hydroxylase (PAH) locus.

PMID- 1361102
TI  - Improved predictive test for MEN2, using flanking dinucleotide repeats and RFLPs.
AB  - Gene(s) for the autosomal dominant endocrine cancer syndromes, multiple endocrine
      neoplasia type 2A (MEN2A), multiple endocrine neoplasia type 2B (MEN2B), and
      familial medullary thyroid carcinoma (MTC1) all map to the pericentromeric region
      of chromosome 10. Predictive testing for the inheritance of mutant alleles in
      individuals at risk for these disorders has been limited by the availability of
      highly informative and closely linked flanking markers. We describe the
      development of eight new markers, including two PCR-based dinucleotide repeat
      polymorphisms and six RFLPs that flank the disease loci. One of the dinucleotide
      repeat markers (sJRH-1) derives from the RBP3 locus on 10q11.2 and has a PIC of
      .88. The other dinucleotide repeat (sTCL-1) defines a new locus, D10S176, that
      maps by in situ hybridization to 10p11.2 and has a PIC of .68. We have
      constructed a new genetic linkage map of the pericentromeric region of chromosome
      10, on the basis of 13 polymorphisms at six loci, which places the MEN2A locus
      between the dinucleotide repeat markers, with odds of 5,750:1 over the next most
      likely position. Using this set of markers, predictive genetic testing of 130 at
      risk individuals from six families segregating MEN2A revealed that 95% were
      jointly informative with flanking markers, representing a significant improvement
      in genetic testing capabilities.

PMID- 1361104
TI  - Apraclonidine and argon laser trabeculoplasty.

PMID- 1361105
TI  - Markers of keratinocyte differentiation in snuff-induced leukoplakia.
AB  - Biopsy specimens from 12 patients who used snuff and had leukoplakia in the
      mucosa of the oral cavity were studied and compared with specimens from their own
      nonleukoplakic oral mucosa, as well as with biopsy specimens from corresponding
      areas of the oral cavity in 12 nonsmoking, nontobacco-using control subjects. The
      biopsy specimens were processed using standard immunohistochemical rabbit
      antibody to human involucrin and mouse antibody to human transglutaminase type I
      as the primary antibodies. A computer-driven light absorbance image analysis
      system was used to determine the optical density of each of the marker-stained
      specimens. Optical density measurements were compared using a one-way analysis of
      variance. The expression of involucrin was significantly higher in the epithelium
      of the nonsmoking, nontobacco-using control subjects (0.2937 +/- 0.0725 optical
      density) in comparison with the normal-appearing mucosa (0.2283 +/- 0.0488
      optical density) and the leukoplakic mucosa of the snuff-using patients (0.2007
      +/- 0.0669 optical density) (p < 0.05). The expression of transglutaminase type I
      was also significantly higher in the epithelium of the nonsmoking, nontobacco
      using controls (0.2308 +/- 0.1381 optical density) than in the patients with
      leukoplakic mucosa (0.1310 +/- 0.0472 optical density) (p < 0.05). However, there
      was no difference when compared with the normal-appearing mucosa of the patients
      in the snuff-using group (0.1686 +/- 0.0323 optical density). This study has
      shown that involucrin and transglutaminase type I are expressed differently in
      leukoplakic oral mucosa of snuff users and in normal oral mucosa and that this
      difference can be measured objectively.

PMID- 1361106
TI  - Oncogene expression in follicular neoplasms of the thyroid.
AB  - Oncogene expression has been found to be a potential marker for aggressive
      biologic behavior in certain tumors. We studied 21 follicular adenomas and 20
      follicular carcinomas by immunocytochemistry utilizing specific monoclonal
      antibodies against HER-2/neu and c-myc oncogenes. Survival data were obtained
      from our institution's tumor registry. No expression of the HER-2/neu oncogene
      was found in the specimens studied. Cytoplasmic staining for c-myc was observed
      in 3 of 21 adenomas (14%) and 9 of 20 (45%) carcinomas (p < 0.05). The incidence
      of local, regional, and distant metastases was not significantly different in c
      myc (+) and c-myc (-) patients. The c-myc oncogene is expressed more often in
      malignant than in benign follicular neoplasms of the thyroid, but its expression
      does not appear to be a good prognostic indicator.

PMID- 1361107
TI  - [Continuous epidural infusion of narcotic analgesics with a view to treating the
      pain syndrome in incurable oncologic patients].

PMID- 1361108
TI  - The Neurobiology of Neurotensin. Proceedings of 2nd International Conference on
      Neurotensin. Palm Beach, Florida, July 8, 1991.

PMID- 1361109
TI  - Distribution of neurotensin receptors in mammalian brain. What it is telling us
      about its interactions with other neurotransmitter systems.

PMID- 1361110
TI  - Neurotensin, antipsychotic drugs, and schizophrenia. Basic and clinical studies.

PMID- 1361112
TI  - Morphological substrate for neurotensin-dopamine interactions in the rat midbrain
      tegmentum.

PMID- 1361111
TI  - Responses of limbic and extrapyramidal neurotensin systems to stimulants of
      abuse. Involvement of dopaminergic mechanisms.
AB  - In summary, we have observed that drugs of abuse, which can cause schizophrenia
      like paranoia, alter striatal and accumbens NT systems in a similar, dramatic
      fashion. The NT responses to these drugs, in particular METH, are mediated by
      activation of DA D1 receptors. We have observed that NMDA-type glutamate
      receptors are essential for the D1-NT interaction. NMDA receptors are selective,
      since they do not contribute to the antagonistic effects of DA D2 receptors on NT
      activity. This observation suggests that NT responses to D1 and D2 regulation are
      mediated through separate and distinct mechanisms. Finally, we found that the
      presence of METH dramatically reduces striatal NT release, which most likely
      leads to NT accumulation in nerve terminals and the observed increase in NT
      tissue level. The blockade of NT release by a psychotogenic drug, such as METH,
      is consistent with the hypothesis that NT has antipsychotic activity and a
      decrease in its release may contribute to some forms of schizophrenia similar to
      that caused by intense use of the stimulants of abuse.

PMID- 1361113
TI  - Intramembrane interactions between neurotensin receptors and dopamine D2
      receptors as a major mechanism for the neuroleptic-like action of neurotensin.
AB  - Evidence has been presented that behavioral actions of NT, inducing its
      neuroleptic-like action, can be explained on the basis of NT-D2 intramembrane
      receptor-receptor interactions in the basal ganglia, unrelated to the coexistence
      phenomenon, leading to reduced affinity and transduction of the D2 agonist
      binding site. By reducing selectively D2 receptor transduction at the pre- and
      postsynaptic level, the NT receptor appears capable of switching the DA synapses
      towards a D1 receptor-mediated transduction, illustrating how receptor-receptor
      interactions can increase the functional plasticity of central synapses (FIG.
      12).

PMID- 1361114
TI  - Interaction between neurotensin and dopamine in the brain. Morphofunctional and
      clinical evidence.

PMID- 1361116
TI  - Physiological mechanisms of the analgesic effect of neurotensin.

PMID- 1361115
TI  - The current status of neurotensin-dopamine interactions. Issues and speculations.

PMID- 1361117
TI  - Differential effects of conditioned and unconditioned stress on the neurotensin
      content of dopamine cell body groups of the ventral mesencephalon.
AB  - The findings of this study extend the observations of Deutch et al. who suggested
      that NT in the ventral mesencephalon may be involved in the environmentally
      elicited activation of selectively responsive populations of mesotelencephalic
      dopamine neurons. The unconditioned response of NT-LI to electric footshock was
      observed only at an intensity of 500 microA and only in the lateral subdivision
      of the VTA. The selective effect of footshock stress on the NT content of a
      specific cell body group of the ventral mesencephalon suggests that NT mechanisms
      in the lateral VTA may, in part, underlie the stress-induced activation of
      dopamine neurons that originate in the lateral VTA. However, it should be noted
      that populations of dopamine neurons are activated by footshock intensities less
      than 500 microA, while NT concentrations of mesencephalic dopamine cell body
      groups are not altered by these shock intensities. The disparity weakens the
      possibility of a role for NT in the stress-induced activation of brain dopamine
      neurons unless NT mechanisms may be involved in transducing the effects of higher
      intensity stressors versus low intensity stressors. However, it should be noted
      that changes in the concentration of NT-LI represent an endpoint of unknown
      sensitivity and functional significance and best serve as an initial
      approximation of the effects of a manipulation on NT-containing neurons. It is
      plausible that NT mechanisms in the ventral mesencephalon may act in concert with
      other neuropeptides such as substance P and Met-enkephalin to transduce the
      effects of stressors on alterations in the activity of mesotelencephalic dopamine
      neurons that originate in the ventral mesencephalon. An examination of the
      effects of footshock stress on the content of prepro-NT mRNA in the dopamine cell
      body groups of the ventral mesencephalon would be of interest in assessing
      whether stress enhances NT gene expression or alters the characteristics of
      release of this neuropeptide in the ventral mesencephalon. Lacking NT receptor
      antagonists, it would also be of interest to determine the effects of the passive
      immunoneutralization of NT in the ventral mesencephalon on footshock-induced
      increases in the biochemically estimated activity of mesotelencephalic dopamine
      neurons to better understand the involvement of NT as a transducer of the effects
      of stress on dopamine neuronal activity. The distinct topography of conditioned
      versus unconditioned stress on the concentration of NT-LI in the dopamine cell
      body groups of the ventral mesencephalon suggests that NT may be involved in the
      differential activation of distinct dopamine neuronal populations by these
      different stressors.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1361118
TI  - Colocalization of neurotensin in the mesocortical dopaminergic system. Restricted
      regional and laminar distribution in rat, lack of colocalization in human.

PMID- 1361119
TI  - Striatal injection of neurotensin increases tyrosine hydroxylase mRNA in
      substantia nigra.

PMID- 1361120
TI  - Expression of the proneurotensin gene in the rat brain and its regulation by
      antipsychotic drugs.
AB  - In this chapter, we have presented evidence for several potential levels of
      interaction of NT/N gene products with dopaminergic systems of the brain. We have
      focused on one manifestation of this interaction related to the effects of
      antipsychotic drugs on expression of the NT/N gene in two anatomically discrete
      populations of neurons. It appears that certain antipsychotic drugs can
      dramatically increase expression of this gene in the dorsolateral striatum by
      blocking dopamine D2 receptors, perhaps by increasing expression of the gene
      encoding the transcriptional regulator fos. In addition, a second group of NT
      cells in the shell region of the nucleus accumbens also respond to these drugs by
      increasing NT/N gene expression. Several other peptides have been suggested to
      respond to treatment with antipsychotic drugs. However, there are some important
      differences with respect to their effects on the NT cells we have studied. The
      most important of these is the differential responsiveness of the DLSt and
      nucleus accumbens NT neurons to typical and atypical antipsychotics. We showed
      that all antipsychotic drugs tested increased NT/N mRNA gene expression in the
      accumbens, a region thought to be involved in dopaminergic disturbances
      underlying psychosis. However, only the typical neuroleptics that have a high
      propensity to induce acute extrapyramidal motor side effects influenced NT/N gene
      expression in the dorsolateral striatum, a structure importantly involved in
      regulation of motor functions. We hypothesize, therefore, that NT/N-expressing
      neuronal systems in the nucleus accumbens may mediate some or all of the
      antipsychotic effects, whereas those in the dorsolateral striatum may be involved
      in motor effects of neuroleptic drugs. Thus, examination of the effects of these
      drugs on these neuronal populations will not only clarify their mechanism of
      action, but in addition may provide a useful "screening" assay for new drugs with
      enhanced antipsychotic activity, but reduced propensity to induce the
      debilitating extrapyramidal side effects that are a major cause of patient
      noncompliance. Future studies will focus on the effects of antipsychotic drugs on
      NT neurons in clinically relevant models of chronic administration, and on the
      molecular events involved in their effects on expression of the NT/N gene in the
      brain.

PMID- 1361121
TI  - [A case of multiple pulmonary metastases from duodenal cancer showing partial
      response using 5'-DFUR and a small dose of MMC].
AB  - A 77-year-old female with primary duodenal cancer had undergone
      pancreatoduodenectomy in May, 1989. Postoperative chemotherapy was done in
      combination with MMC (mitomycin C), lentinan and UFT (combined medicine of
      tegafur and uracil). In August, 1991, the patient complained of a cough and then
      was examined for multiple pulmonary metastases from duodenal cancer by chest X
      ray and CT-scan. Then, she received 5'-DFUR (400-800 mg) and MMC (total 6 mg).
      Two months from the start of this therapy, the cough almost vanished and
      pulmonary lesions were diminished markedly. For about five months, this case
      corresponded to partial response (PR) according to the response criteria proposed
      by Koyama-Saitoh. The side effects of 5'-DFUR were diarrhea and anorexia.
      Therefore, we think that 5'-DFUR and a small dose of MMC yielded a partial
      response to multiple pulmonary metastases from duodenal cancer.

PMID- 1361122
TI  - Morphine analgesia in normal and alloxanized mice.
AB  - The analgesic response to 10 mg/kg of morphine hydrochloride, administered
      intraperitoneally, was examined in mice made diabetic by treatment with alloxan
      using the hot plate method. The hot plate base line latency of diabetic mice was
      significantly higher than that of normal mice. Morphine was found to possess an
      hyperglycaemic effect in both normal and diabetic mice. A decreased analgesic
      response to morphine was observed in diabetic mice. The decreased response seemed
      to be associated with plasma glucose levels, since multiple injections of insulin
      replacement abolished the decrease in morphine analgesia in diabetic mice.
      However, a single injection of insulin or glucose loading did not modify morphine
      analgesia. Naloxone was an effective antagonist of the analgesic and
      hyperglycaemic effects of morphine in both normal and diabetic mice, but induced
      a greater reduction of the plasma glucose level in diabetic than in normal mice.
      It is suggested that a supranormal dose of morphine may be needed in diabetics.

PMID- 1361123
TI  - Effects of nipradilol on the microvascular tone of rat mesentery: comparison with
      other beta-blockers and vasodilators.
AB  - The effects of nipradilol, a nonselective beta-blocker with vasodilator
      activities, on the diameter of arterioles and venules were examined in rat
      mesentery in vivo and were compared with those of propranolol, atenolol,
      labetalol, nifedipine and nitroglycerin. Topical application of nipradilol (10(
      7) M and 10(-6) M) dilated the arterioles significantly to 109 +/- 2% and 112 +/-
      2% of control, respectively (mean +/- S.E.; n = 9; p < 0.01), without changes in
      blood pressure and pulse rate. The dilator effect was comparable to that of
      nifedipine and nitroglycerin. Propranolol constricted the arterioles (to 86 +/-
      3% at 10(-7) M; n = 9; p < 0.01), but atenolol and labetalol had no significant
      effects. Nitroglycerin dilated venules significantly (to 108 +/- 2% at 10(-7) M;
      n = 6; p < 0.01) but other drugs showed no significant effects on the tone of
      venules. Unlike the other beta-blockers used in this study, nipradilol has
      dilator effects on arterioles as have nifedipine and nitroglycerin.

PMID- 1361124
TI  - Regulated Ca2+ signalling through leukocyte CD11b/CD18 integrin.
AB  - General mechanisms of adhesion in the immune response are coordinated by the
      leukocyte integrins CD11/CD18. The possible participation of these
      differentiation molecules in early events of transmembrane signalling was
      investigated. Monoclonal antibody (mAb) cross-linking of CD18, the integrin beta
      subunit ubiquitously expressed by all leukocytes, increased the cytosolic free
      Ca2+ concentration ([Ca2+]i) by 2-3-fold in monocyte THP-1 cells. Digitalized
      imaging in single adherent cells showed that this Ca2+ response is temporally
      biphasic, involves both release of Ca2+ from the intracellular stores as well as
      Ca2+ influx from the external compartment, and is dramatically down-modulated by
      terminal differentiation of THP-1 cells to a mature monocyte phenotype.
      Similarly, only a minor subset of 20-30% of peripheral blood monocytes
      heterogeneously maintain the CD18-mediated Ca(2+)-signalling properties. Cross
      linking of CD18 also increased cytosolic free [Ca2+]i in a subset of approx. 15
      20% of resting T lymphocytes, in a Ca2+ response that was completely abrogated
      during T-cell mitogenic activation with lectins or alloreactive antigen. While
      cross-linking of CD11a or CD11c was without effect, occupancy of CD11b increased
      cytosolic free [Ca2+]i in monocytic cells. This response was functionally coupled
      with a transient activation state of CD11b/CD18, which was reflected in its
      increased avidity to bind the complementary ligand fibrinogen. These results
      suggest that occupancy of CD18 transduces a stimulatory Ca2+ signal that is
      critically regulated by the state of cell activation/differentiation and by the
      association with the unique alpha-subunit CD11b. These intrinsic signalling
      properties may directly participate in regulating the oligospecific ligand
      recognition of leukocyte integrins.

PMID- 1361125
TI  - Microtubule-independent choleresis and anti-cholestatic action of
      tauroursodeoxycholate in colchicine-treated rat liver.
AB  - In order to cast light on the anti-cholestatic and cytoprotective properties of
      ursodeoxycholic acid (UDCA), intrahepatic transport and secretion of bile salts
      and biliary phospholipids were investigated by using isolated perfused livers
      from colchicine-pretreated rats. Administration of taurocholic acid (TCA) after
      colchicine pretreatment induced marked cholestasis. Tauroursodeoxycholic acid
      (TUDCA) treatment, in contrast, was associated with maintenance of bile flow,
      with excretion rates of bile acids and phospholipids similar to those in control
      animals. Furthermore, TCA-induced cholestasis in colchicine-treated rat livers
      was clearly decreased by co-administration of TUDCA. Although simultaneous
      addition of UDCA also showed slight improvement, with or without taurine pre
      treatment, biliary bile-salt analysis also showed that cholestasis was markedly
      remitted as the excretion of taurine-conjugated UDCA was increased. The results
      suggest that the cytoprotective and anti-cholestatic effects of TUDCA may be
      linked to action at the intrahepatocyte level, represented by mild detergent
      effects on organelle lipids and preservation of intracellular transport even
      under microtubule-dysfunctional conditions. In addition, it was indicated that
      cytoprotective effects of UDCA may also be exerted after its conjugation with
      taurine inside hepatocytes.

PMID- 1361126
TI  - T cells and eosinophils in the pathogenesis of asthma.
AB  - Persistent asthma is characterized by chronic inflammation of the bronchial
      mucosa, where T cells and eosinophils are prominent. This article summarizes the
      evidence that asthmatic bronchial inflammation is initiated and propagated by
      cytokines secreted by activated T cells and other cells, and describes how the
      release of specific cytokines could result in local preferential accumulation and
      activation of eosinophils.

PMID- 1361127
TI  - BMY-14802 reverses the reduction of striatal dopamine release induced by (+)-3-[3
      hydroxyphenyl]-N-(1-propyl)piperidine.
AB  - Intraperitoneal injection of (+)-3-[3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)
      3PPP), a sigma receptor agonist, significantly reduced the striatal levels of
      dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
      measured by in vivo microdialysis. These reductions were significantly greater at
      (+)-3PPP doses of 12 and 24 mg/kg than at 1 mg/kg. The levels of 5
      hydroxyindoleacetic acid (5HIAA) were increased by the injection of (+)-3PPP in
      dose of 24 mg/kg, but were not affected at lower doses. BMY-14802, a sigma
      antagonist, alone at doses of 15 mg/kg and 30 mg/kg did not affect the levels of
      DA, DOPAC, HVA and 5HIAA. Pretreatment with 30 mg/kg BMY-14802 reversed the
      reduction of the levels of DA induced by 12 mg/kg (+)-3PPP. Although neither 30
      mg/kg BMY-14802 nor 12 mg/kg (+)-3PPP affected the levels of striatal 5HIAA,
      combined treatment with both produced a significant elevation. These findings
      clearly demonstrate that sigma receptors may regulate DA release from the
      striatal presynapse.

PMID- 1361128
TI  - Synaptically activated increases in Ca2+ concentration in hippocampal CA1
      pyramidal cells are primarily due to voltage-gated Ca2+ channels.
AB  - Changes in intracellular Ca2+ concentration ([Ca2+]i) in the soma and dendrites
      of hippocampal CA1 pyramidal neurons were measured using intracellularly injected
      fura-2. A large component of the [Ca2+]i elevation caused by high frequency
      stimulation of the Schaffer collaterals was correlated with the Na+ spikes
      triggered by the excitatory postsynaptic potentials (EPSPs). These spikes were
      generated in the soma and proximal dendrites and stimulated Ca2+ entry through
      voltage-gated Ca2+ channels. Suppressing spikes by hyperpolarizing the soma or by
      injecting QX-314 revealed a smaller nonspike component of Ca2+ entry. A
      substantial fraction of this component was mediated by the action of the EPSPs on
      voltage-gated Ca2+ channels, because it persisted in 2-amino-5-phosphonovaleric
      acid and because it was usually reduced when Ca2+ channel activity was suppressed
      by hyperpolarization. Ca2+ entry through the N-methyl-D-aspartate receptor
      channel could not be detected with certainty, perhaps because it was highly
      localized.

PMID- 1361130
TI  - Is a high rate of cell proliferation carcinogenic in itself?

PMID- 1361129
TI  - Ca2+ entry via postsynaptic voltage-sensitive Ca2+ channels can transiently
      potentiate excitatory synaptic transmission in the hippocampus.
AB  - We have studied the role of Ca2+ entry via voltage-sensitive Ca2+ channels in
      long-term potentiation (LTP) in the CA1 region of the hippocampus. Repeated
      depolarizing pulses, in the presence of the NMDA receptor antagonist D-APV and
      without synaptic stimulation, resulted in a potentiation of excitatory
      postsynaptic potentials (EPSPs) or currents (EPSCs). This depolarization-induced
      potentiation was augmented in raised extracellular Ca2+ and was blocked by
      intracellular BAPTA, a Ca2+ chelator, or by nifedipine, a Ca2+ channel
      antagonist, indicating that the effect was mediated by Ca2+ entry via voltage
      sensitive Ca2+ channels. Although the peak potentiation could be as large as 3
      fold, the EPSP(C)s decayed back to baseline values within approximately 30 min.
      However, synaptic activation paired with depolarizing pulses in the presence of D
      APV converted the transient potentiation into a sustained form. These results
      indicate that a rise in postsynaptic Ca2+ via voltage-sensitive Ca2+ channels can
      transiently potentiate synaptic transmission, but that another factor associated
      with synaptic transmission may be required for LTP.

PMID- 1361131
TI  - Toxicology of sensory systems: a perspective.
AB  - This brief review is the result of a recent meeting of the British Toxicology
      Society (Toxicology of Sensory Systems, University of York, April 2-3, 1992). The
      meeting provided the opportunity to discuss the anatomy, physiology and function
      of the eye, ear, nasal epithelium and peripheral sensation and the methods that
      are available to detect injury or dysfunction both in the preclinical and
      clinical situation. In addition, the mechanism whereby certain chemicals can
      perturb some of these organs was discussed. The aim of this short article is to
      highlight some of the recent advances in understanding in these areas with regard
      to their relevance or impact on toxicology. For convenience the areas will be
      discussed under separate headings.

PMID- 1361132
TI  - Dose selection for toxicity studies: a protocol for determining the maximum
      repeatable dose.
AB  - 1. A three-stage protocol is described for a dose-ranging study which defines the
      maximum repeatable dose (MRD) and provides a preview of the toxicology of new,
      pharmacologically active, substances before commencing the first formal
      regulatory toxicity studies, usually of 2 or 4 weeks duration. 2. Additionally, a
      range of toxicokinetic (TK) data relevant to protocol design for formal studies
      is generated. 3. Stage A is a dose incrementation process in which the MRD is
      provisionally determined and basic TK values generated. 4. In stage B the animals
      are dosed daily for at least 7 d, the MRD is substantiated and a wider range of
      TK data obtained. 5. In stage C, each of the dose levels identified for a formal
      study is administered once to investigate the relationship of doses to TK data.
      6. This protocol can be completed using as few as 24 rats or six dogs (or
      primates). 7. Selection of dose levels for the first formal studies can be
      greatly aided by the results of a well-designed dose-ranging study including TK
      data. 8. For particularly toxic substances, the findings of studies based on this
      protocol have frequently been sufficiently clear to warrant early termination of
      their development.

PMID- 1361133
TI  - Clinical course, therapy, outcome and analytical data in amitriptyline and
      combined amitriptyline/chlordiazepoxide overdose.
AB  - A total of 103 cases of amitriptyline (AT) overdose (group 1) and 81 cases of
      overdose with a fixed combination of AT and chlordiazepoxide (CDE) (group 2),
      treated at our Intensive Care Unit or reported to our Poison Information Center
      between 1985-1990, were evaluated with respect to clinical course, symptoms and
      outcome, as well as efficacy of therapy. The mean amount of AT was considerably
      higher in group 1 compared to group 2 (13 mg kg-1 vs 7.7 mg kg-1). The most
      frequent symptoms in both groups were impaired consciousness, anticholinergic
      symptoms, seizures, arrhythmia and hypotension. Respiratory insufficiency
      necessitated respirator therapy in 63 of the patients. Two patients in group 1
      and one patient in group 2 did not survive. Therapy included primary
      detoxification by gastric lavage and repeated administration of activated
      charcoal. In four of eight patients with cardiac conduction disturbances,
      hypertonic sodium bicarbonate led to a significant reduction in QRS duration and
      AV interval. Physostigmine was effective in eight of 14 patients with pronounced
      anticholinergic symptoms. No effect was observed in the other six patients.
      Haemoperfusion, which was performed in five patients, led to rapid improvement of
      coma after initiation of therapy in four patients. The clinical efficacy of
      haemoperfusion in AT overdose despite the high volume of distribution of AT
      deserves further investigation. The rather high average overdose of AT implies
      that large package sizes of AT were available to the patients. A major step
      towards prevention of serious AT overdose would be the prescription of package
      sizes containing a total of less than 500 mg AT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361134
TI  - Respiratory symptoms and ventilatory capacity in metal polishers.
AB  - To evaluate the long-term effects of metal dusts on the bronchopulmonary system
      and the synergistic effect of cigarette smoke, a comparative study of spirometric
      measurements in 104 polishers and 90 unexposed controls was carried out in 25
      brass and steelware polishing industries at Moradabad in northern India. The two
      groups were comparable in terms of age, height, smoking habit and socio-economic
      status. A total of 58.6% of the polishers had one or more respiratory symptoms,
      compared to only 25.5% of the controls (P < 0.05). Chronic cough was present in
      21 polishers (20.2%) as compared to 11.1% of the controls. However, this
      difference was insignificant. Chronic phlegm was nearly three times as frequent
      among the polishers as among the controls (17.5% vs 4.4%) (P < 0.005). The
      prevalence of dyspnoea of varying grades was also significantly higher (16.3% as
      opposed to 4.4%) among the exposed groups. Chronic bronchitis (6.7%) and
      occupational asthma (4.8%) were found to be confined to polishers. The polishers
      also experienced acute respiratory symptoms during the work shift. The prevalence
      of acute respiratory symptoms was recorded for cough in 19 workers (44.1%)
      followed by dyspnoea in 14 workers (32.5%) and throat irritation in 11 workers
      (25.5%). Comparison of the mean values of pulmonary function parameters in the
      polishers and the controls showed significant differences in the smoking and non
      smoking groups (P < 0.001). The polishers exhibited significantly greater acute
      reductions in various lung functions over the work shift, particularly for forced
      expiratory flow over the 25-75% portion of the spirogram (FEF25-75%) FEF25% and
      FEF50%, than did the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361135
TI  - Pesticide-related incidents treated in Finnish hospitals--a review of cases
      registered over a 5-year period.
AB  - Pesticide-related incidents are uncommon in Finland. They comprised 0.11% of all
      hospitalizations due to poisoning in 1987-88. A search of the nationwide Hospital
      Discharge Register revealed 78 pesticide-related incidents in a 5-year period.
      Some 30 different agents were involved, the most frequent being organophosphate
      and MCPA. Only 36 cases (46%) were judged to be unequivocal or probable pesticide
      poisonings; 26 (33%) were probably other illnesses because of no or minimal
      exposure and of the children admitted for follow-up, nine (12%) had potentially
      marked exposure, but no poisoning developed owing to vigorous early treatment
      which limited absorption, and seven (9%) cases remained undetermined. According
      to our analysis, the management of patients with (suspected) pesticide poisoning
      at hospitals could be further improved if the following procedures were
      emphasised: decontamination of the skin when appropriate, systematic early
      estimation of the likely dose involved, analytical verification of pesticide
      absorption whenever feasible, and consistent collaboration with a toxicological
      advisory service.

PMID- 1361136
TI  - Podophyllotoxin intoxication: toxic effect of Bajiaolian in herbal therapeutics.
AB  - Bajiaolian (Dysosma pleianthum), one species in the Mayapple family, has been
      widely used as a general remedy and for the treatment of snake bite, weakness,
      condyloma accuminata, lymphadenopathy and tumours in China for thousands of
      years. However, the textbooks of traditional Chinese medicine mention little
      about the toxicity of Bajiaolian. Within 1 year, the authors saw five people who
      manifested nausea, vomiting, diarrhoea, abdominal pain, thrombocytopenia,
      leucopenia, abnormal liver function tests, sensory ataxia, altered consciousness
      and persistant peripheral tingling or numbness after drinking infusions made with
      Bajiaolian. The herb was recommended by either traditional Chinese medical
      doctors or herbal pharmacies for postpartum recovery and treatment of a neck
      mass, hepatoma, lumbago and dysmenorrhoea. Podophyllotoxin is one of the main
      ingredients of the Bajiaolian root. The clinical manifestations observed in our
      patients were consistent with podophyllum intoxication. Podophyllotoxin
      intoxication usually results from the accidental ingestion or topical application
      of podophyllum resin. However, these cases of Bajiaolian intoxication were
      iatrogenic and results from 'therapeutic doses' of Bajiaolian cited in the
      textbooks of traditional Chinese medicine.

PMID- 1361137
TI  - Effect of glycol ethers on plasma osmolality.
AB  - 1. Glycol ethers and their alkoxyacetic acid metabolites produce a linear
      increase in plasma osmolality with increasing plasma concentration. 2. This
      change in osmolality may be too small to be clinically useful at concentrations
      expected in cases of acute human glycol ether poisoning.

PMID- 1361138
TI  - Failure of oral activated charcoal to accelerate the elimination of amiodarone
      and chloroquine.
AB  - 1. The effect of activated charcoal on the elimination of amiodarone and
      chloroquine was studied in the rat. 2. The study consisted of two separate
      experiments. Amiodarone and chloroquine were injected subcutaneously at doses of
      200 mg kg-1 and 100 mg kg-1, respectively. Six rats in both experiments were put
      on a charcoal-containing diet 48 h after drug administration, while the control
      groups remained on a normal diet. 3. Treatment with repeated oral activated
      charcoal had no effect on the true elimination of amiodarone and chloroquine. 4.
      These results suggest that, after the distribution of amiodarone and chloroquine
      into peripheral compartments, their rate of elimination cannot be significantly
      accelerated with multiple oral doses of activated charcoal.

PMID- 1361139
TI  - Efficacy of whole bowel irrigation using solutions with or without adsorbent in
      the removal of paraquat in dogs.
AB  - 1. The efficacy of whole bowel irrigation with a solution containing either
      polyethylene glycol (PEG) with electrolyte or an adsorbent (Kayexalate with a
      cathartic (sorbitol) was investigated in 18 dogs who had been given 250 mg kg-1
      paraquat dichloride via a jejunal tube to eliminate the influence of gastric
      absorption. 2. Plasma paraquat concentrations 2 and 3 h after the initiation of
      bowel irrigation and at the end of the study (5 h later) were significantly lower
      in the bowel irrigation groups than in the control (no bowel irrigation) group.
      3. The total body clearances of paraquat in the bowel irrigation groups were
      significantly greater than in the control group. 4. There were no significant
      differences between the two different irrigation solution groups in plasma
      paraquat concentration, the area under the plasma concentration time curve and
      the total body clearance. 5. In the PEG with electrolyte group, about 70% of the
      administered dose of paraquat was removed by means of bowel irrigation (n = 4).
      6. The adjunction of the adsorbent had no beneficial effects. 7. Haemodynamic
      changes associated with whole bowel irrigation were unremarkable except that
      right atrial and pulmonary arterial pressures were elevated in the latter part of
      the study.

PMID- 1361141
TI  - Toxicokinetics of colchicine in humans: analysis of tissue, plasma and urine data
      in ten cases.
AB  - 1. A specific and sensitive radioimmunoassay was used to study the toxicokinetics
      of colchicine in seven cases of acute human poisoning. Post-mortem tissue
      concentrations of colchicine were measured in three further cases. Depending on
      the time of patient admission, two disposition processes could be observed. The
      first, in three patients, admitted early, showed a bi-exponential plasma
      colchicine decrease, with distribution half-lives of 30, 45 and 90 min. The
      second, in four patients, admitted late, showed a mono-exponential decrease.
      Plasma terminal half-lives ranged from 10.6 to 31.7 h for both groups. 2.
      Pharmacokinetic analysis of urine colchicine data was performed for two patients.
      The fraction of unchanged colchicine excreted in urine was about 30%, renal
      clearance was about 13 l h-1 and three-fold less than total body clearance (39 l
      h-1). The apparent volume of distribution was 21 l kg-1. 3. Post-mortem tissue
      analysis showed an ubiquitous colchicine distribution. Colchicine accumulated at
      high concentrations in the bone marrow (more than 600 ng g-1), testicle (400 ng g
      1), spleen (250 ng g-1), kidney (200 ng g-1), lung (200 ng g-1) and heart (95 ng
      g-1); it was also found in the brain (125 ng g-1). 4. This toxicokinetic study
      shows that after massive ingestion, the disposition parameters and kinetics of
      colchicine are not markedly modified from those occurring in healthy volunteers.
      The absorption process was not delayed and the distribution and elimination half
      lives were in the range known to occur with therapeutic doses.

PMID- 1361140
TI  - Corticosterone does not cause testicular toxicopathology in the rat: relevance to
      methylxanthines, ACTH and stress.
AB  - 1. Methylxanthines, ACTH and stress are well known to produce testicular
      pathology (e.g. seminiferous tubule atrophy). Methylxanthines, ACTH and stress
      alter hormone secretion, particularly from the pituitary-adrenocortical system.
      Consequently, it has recently been suggested that there may be a causal
      relationship between changes in endogenous physiological adrenocortical
      secretions, particularly corticosterone, and testicular pathology. 2. This study
      tested the hypothesis that corticosterone mediates the testicular effects of both
      methylxanthine treatment and stress. Corticosterone was administered daily by
      subcutaneous injection to groups of 10 male rats at dose levels of 2 or 20 mg kg
      1 in propylene glycol (1 ml kg-1) for 1 month (the shortest duration of
      methylxanthine or ACTH exposure known to produce testicular pathology). The
      highest dose of corticosterone resulted in plasma concentrations that closely
      matched values resulting from stress (200-700 ng ml-1) compared with controls (<
      25 ng ml-1). 3. The highest dose of corticosterone caused reduced body weight
      gain, lower thymus, adrenal, seminal vesicle and prostate weights, but did not
      induce any testicular pathology. 4. That a high, but physiologically relevant,
      dose of corticosterone did not cause testicular pathology in this experiment
      excludes this steroid in the direct aetiology of methylxanthine, ACTH and stress
      induced testicular pathology. Other steroids secreted from the adrenal, in
      combination with corticosterone, may be involved.

PMID- 1361142
TI  - Long-term study of brain lesions following soman, in comparison to DFP and
      metrazol poisoning.
AB  - The long-term histopathological effects of acute lethal (95 micrograms kg-1) and
      sublethal (56 micrograms kg-1) doses of soman were studied in rats and were
      compared to lesions caused by equipotent doses of either another cholinesterase
      (ChE) inhibitor, DFP (1.8 mg kg-1), or a non-organophosphorus convulsant,
      metrazol (100 mg kg-1). Severe toxic signs were noted following one LD50 dose
      administration of all the compounds, yet only soman induced brain lesions.
      Moreover, even when administered at a sublethal dose (0.5 LD50), soman induced
      some histological changes without any clinical signs of intoxication. Soman
      induced brain lesions were assessed quantitatively using a computerized image
      analyser. The analysis was carried out for up to 3 months following
      administration, and a dynamic pattern of pathology was shown. The cortical
      thickness and area of CA1 and CA3 cells declined significantly as early as 1 week
      post-exposure. No pathological findings were detected following DFP and metrazol
      administration. It is therefore suggested that brain lesions are not common for
      all ChE inhibitors and that convulsions per se are not the only factor leading to
      brain damage following the administration of soman. The degenerative process
      (found also with the sublethal dose of soman) might be due to a secondary effect,
      unrelated to soman's clinical toxicity, but leading to long-term brain injuries.

PMID- 1361143
TI  - Diquat-induced intestinal secretion in the anaesthetized rat.
AB  - 1. Diquat (1,1'-ethylene-2,2'-bipyridilium) is a non-selective desiccant
      herbicide which, when administered orally to mammalian species, causes
      significant secretion of fluid into the lumen of the gastrointestinal tract. In
      order to characterize this secretory response in more detail the effect of
      sublethal doses of diquat dibromide (DQBr2) on intestinal secretion was
      investigated in vivo in the jejunum of anaesthetized rats. 2. Ligated segments of
      jejunum (10 cm) which were prepared in groups of up to five animals were filled
      with 500 microliters of isosmotic DQBr2 solutions with concentrations ranging
      from 1-100 mM and maintained in the anaesthetized rat for 1, 2 or 3 h; in control
      experiments a solution of 100 mM NaBr was used. 3. It was found that while all of
      the fluid instilled into the segments was absorbed in the control experiments,
      there was both a dose- and time-dependent secretory response to DQBr2. Maximal
      fluid secretion occurred after treatment with 50 mM DQBr2 for 3 h. 4.
      Histological assessment of the jejunum revealed an increase in cell exfoliation
      and evidence of luminal distension after incubation with DQBr2. However, no
      structural damage to the mucosa could be seen to account for the fluid secretion.
      5. The model described provides a quantitative means of evaluating intestinal
      secretion and may be used for elucidating the mechanism by which diquat alters
      fluid transport processes.

PMID- 1361145
TI  - Neurotoxic effects induced by intracerebral and systemic injection of paraquat in
      rats.
AB  - 1 The neurotoxic effects elicited by paraquat after systemic and intracerebral
      injection were studied in rats. 2 Intrahippocampal microinfusion of paraquat (0.1
      mumol) produced behavioural stimulation and electrocortical (ECoG) excitation
      followed, at 24 h, by multifocal brain damage. Similarly, microinfusion of
      paraquat (0.2-0.4 mumol) into the locus coeruleus, substantia nigra or into the
      raphe nuclei, where noradrenergic, dopaminergic and serotonergic neurons are
      present, respectively, elicited potent excitotoxic effects (n = 6 rats per dose
      and area). A lower dose (0.01 mumol) of the herbicide or injection of the vehicle
      (1.0 microliter) did not produce any behavioural, ECoG or neurodegenerative
      effect. 3 After systemic administration, paraquat (20 mg kg-1 s.c.) evoked limbic
      motor seizures and ECoG epileptogenic discharges; in 10 out of 15 treated rats
      neuronal cell death was observed in the pyriform cortex, but not in other brain
      regions. A dose of 5 mg kg-1 was ineffective. 4 Among the regions of the brain
      studied, high concentrations of paraquat were detected in the pyriform cortex 24
      h after systemic administration (5.0 and 20 mg kg-1 s.c.) lower levels being
      observed in the caudate nucleus. 5 In conclusion, paraquat, given systemically or
      intracerebrally in rats produces neurodegenerative effects.

PMID- 1361144
TI  - Intrapleural administration of fibres induces mesothelioma in rats in the same
      relative order of hazard as occurs in man after exposure.
AB  - 1. The dose-response data for the induction of mesothelioma, in rats, by the
      intrapleural administration of the fibrous zeolite, erionite, has been compared
      to the published data for the crocidolite and chrysotile forms of asbestos.
      Erionite is more than two orders of magnitude more carcinogenic than either of
      the two forms of asbestos examined. 2. The relative sensitivity of the
      intrapleural and intraperitoneal routes of injection were also examined. The
      sensitivity of the intraperitoneal over the intrapleural route of administration
      was considerably greater for all the forms of asbestos examined but not for
      erionite. 3. The relationship for different fibres, between the number of fibres
      required to give animals mesothelioma, at the 50% or 10% observable tumour effect
      level (OTEL) was examined, and a ranking of relative carcinogenicity was made. 4.
      This showed that the data derived from the dose responses obtained by the
      intrapleural administration of fibres to rats ranked the relative carcinogenicity
      of erionite, crocidolite and chrysotile in accord with the known clinical
      mesothelioma induction in man after exposure to these fibres. Examination of the
      carcinogenicity ranking from data derived from intraperitoneal injections of
      fibres was not in accord with the known clinical mesothelioma induction in man
      for the various asbestos types examined.

PMID- 1361146
TI  - Double fatal inhalation of dichloromethane.
AB  - 1 Two cases of lethal poisoning following acute inhalation of extremely high
      concentrations of dichloromethane (DCM) are reported. The concentrations of the
      solvent found in the blood of the two subjects collected at autopsy and analysed
      by gas chromatography/mass spectrometry (572 and 601 mg l-1) were compatible with
      those measured in the air a few hours after the discovery of the bodies (up to
      168,000 ppm). 2 Extensive brain and lung oedema and congestion, microhaemorrhagic
      changes of the stomach and congestion in other organs were observed on
      macroscopic and microscopic examination of both subjects. In addition, and in
      both cases, high but not lethal carboxyhaemoglobin (COHb) levels (30%) were found
      in the blood collected at autopsy. 3 Narcosis and respiratory depression due to
      the effect of DCM on the central nervous system (CNS) appear to have played a
      critical role in the death of the two men. However, biotransformation of the
      solvent to toxic metabolites, including carbon monoxide (via oxidative
      dehalogenation by the cytochrome P450-dependent mixed function oxidase system) or
      formaldehyde, formic acid, inorganic chloride and carbon dioxide (via the
      glutathione-S-transferase pathway) may have also contributed significantly to
      fatal toxicity.

PMID- 1361147
TI  - Safety warnings and first aid instructions on consumer and pharmaceutical
      products in Nigeria: are they adequate?
AB  - An investigation into the adequacy of safety warnings and first aid instruction
      on 357 consumer and pharmaceutical product labels was carried out. The results
      show that 23% of the products carried correct and appropriate information while
      34% had neither warning nor first aid instructions. About 15% had copiously
      written instructions and/or warnings and 15% showed partially correct
      instructions. Only about 4% of the products described warning signs and gave
      directions for the full treatment of poisoning and 3% recommended calling a
      health professional in the case of poisoning.

PMID- 1361148
TI  - Clinical experience in the therapy of bites from exotic snakes in Berlin.
AB  - Since there are nearly no indigenous poisonous snakes in Germany, snake bites by
      poisonous snakes are rare. Most serious snake bites reported to poison
      information centres or treated at hospitals are caused by exotic snakes that are
      kept in private households. Only few types of antivenom are stored in emergency
      depots in Germany including polyvalent antivenoms from commercial sources. Since
      experience with the treatment of poisonous snake bites is limited, the records of
      the Intensive Care Unit and the Poison Information Centre of the
      Universitatsklinikum Rudolf Virchow from 1980-1991 were evaluated. During this
      period, 51 snake bites were reported. Eleven patients who had been bitten by
      exotic poisonous snakes were treated in intensive care. In eight of the cases,
      ethanol (blood levels on admission 1.2-4.2 g-1) had played an important role in
      the cause of the bite. A moderate to severe local inflammation at the site of the
      bite followed by oedema and necrosis was typical. One patient developed
      respiratory failure, probably because of the neurotoxic effects of the snake
      venom and a compartment syndrome necessitating fasciotomy. Haemolysis was
      observed in four patients and coagulopathy in six patients. All patients received
      polyvalent antivenom within 2-12 h of the snake bite. Despite serious
      coagulopathy in two of the patients and respiratory arrest in one, all survived
      without sequelae.

PMID- 1361149
TI  - Difenacoum poisoning as a cause of haematuria.
AB  - A man presented with frank haematuria and a grossly prolonged prothrombin time.
      He was later found to have taken an overdose of difenacoum--a 'superwarfarin'
      rodenticide. The diagnosis was confirmed by a serum concentration of difenacoum
      of 0.6 micrograms ml-1. Overdosage with superwarfarins is discussed and the need
      for prolonged treatment with vitamin K1 highlighted.

PMID- 1361150
TI  - Glutathione conjugation and pharmacokinetics of 2-bromo-3-phenylpropionic acid in
      vitro and in the rat in vivo.
AB  - Glutathione (GSH) conjugation of the chiral compound 2-bromo-3-phenylpropionic
      acid (BPP) was studied in vitro and in the rat in vivo. GSH conjugation of BPP,
      catalyzed by a mixture of glutathione-S-transferases (GST's) from rat liver
      cytosol in vitro, was stereoselective: at a substrate concentration of 250
      microM, (R)-BPP was more rapidly conjugated than (S)-BPP (R/S-ratio = 2.6). The
      blood elimination kinetics of the separate BPP enantiomers and the biliary
      excretion kinetics of the corresponding GSH conjugates were studied in the rat in
      vivo after administration of (R)- or (S)-BPP at a dose level of 50 mumol/kg.
      Elimination of (R)-BPP from blood was faster than that of (S)-BPP: half lives
      were 9 +/- 2 min for (R)-BPP and 13 +/- 1 min for (S)-BPP. The biliary excretion
      rate of the GSH conjugate of (R)-BPP declined monoexponentially, while that of
      the GSH conjugate of (S)-BPP displayed a biphasic profile. Half lives of
      excretion were 13 +/- 1 for the GSH conjugate of (R)-BPP, and 11 +/- 2 for the
      GSH conjugate of (S)-BPP (second phase). The first phase in the biliary excretion
      of the GSH conjugate of (S)-BPP could not be attributed to capacity limitation of
      biliary transport carriers as higher excretion rates were attained upon
      administration of higher doses (100 and 200 mumol/kg) of (S)-BPP). The blood
      elimination profiles of (R)- and (S)-BPP differed greatly from the biliary
      excretion profiles of the corresponding GSH conjugates. This suggests that the
      kinetics of BPP conjugate excretion are determined by other processes than
      hepatic GSH conjugation.

PMID- 1361151
TI  - Resolution and adrenergic activities of the optical isomers of 4-[1-(1
      naphthyl)ethyl]-1H-imidazole.
AB  - Recently we synthesized a naphthalene analog of medetomidine, 4-[1-(1
      naphthyl)ethyl]-1H-imidazole hydrochloride (1), and found it to be highly potent
      in adrenergic systems. The separation of optical isomers of this naphthalene
      analog was achieved by using the isomers of tartaric acid. The optical purities
      of the isomers were determined by HPLC using a chiral column. Using X-ray
      analysis the (+)-isomer was determined to have the S absolute configuration. It
      has been reported that the (+)-isomer of medetomidine (2) is the most potent
      enantiomer on alpha 2-adrenergic receptors. There were both qualitative and
      quantitative differences in biological activities of the optical isomers of 1 in
      alpha 1- and alpha 2-adrenergic receptor systems of guinea pig ileum and human
      platelets. (+)-(S)-1, but not (-)-(R)-1 was a selective agonist of alpha 2
      mediated responses in ileum whereas (-)-(R)-1 was more potent than (+)-(S)-1 as
      an inhibitor of alpha 2-mediated platelet aggregation.

PMID- 1361152
TI  - PCNA-dependent DNA polymerase delta from rabbit bone marrow.
AB  - Proliferating cell nuclear antigen (PCNA) and PCNA-dependent DNA polymerase delta
      were partially purified and characterized from rabbit bone marrow. Rabbit DNA
      polymerase delta sediments at 8.2 S upon glycerol density gradient
      centrifugation. Similar to calf thymus PCNA-dependent DNA polymerase delta, a 125
      123-kDa doublet and 48-kDa polypeptides correlate with DNA polymerase activity.
      Western blotting of rabbit DNA polymerase delta with polyclonal antibody to calf
      thymus PCNA-dependent DNA polymerase delta gives the same results as calf thymus
      delta; the 125-123-kDa doublet is recognized. PCNA-dependent DNA polymerase delta
      is resistant to inhibition by dideoxynucleotides and is relatively insensitive to
      inhibition by N2-[p-(n-butyl)phenyl]dGTP. A 3'-->5' exonuclease copurifies with
      the DNA polymerase. The processivity of DNA polymerase delta alone is very low
      but greatly increases with the addition of PCNA from rabbit bone marrow or calf
      thymus. Comparative studies of the original DNA polymerase delta from rabbit bone
      marrow demonstrate a lack of recognition by antibodies to calf thymus delta and a
      high degree of processivity in the absence of PCNA. Additionally, the originally
      described DNA polymerase delta is a single polypeptide of 122 kDa. These features
      would recategorize the original delta to the epsilon category by recently
      proposed convention. PCNA-dependent DNA polymerase delta is a relatively minor
      component of rabbit bone marrow compared to DNA polymerase alpha and PCNA
      independent DNA polymerase delta (epsilon), the relative proportions being alpha,
      60%; delta, 7%; and epsilon, 30%.

PMID- 1361153
TI  - Determination of immunoreactivity of doxorubicin antibody immunoconjugates by a
      Le(y) competitive RIA.
AB  - Many monoclonal antibody-drug immunoconjugates have been evaluated for their
      ability to deliver cytotoxic drugs to tumors. It is essential to establish that
      the ability of the conjugates to bind antigen, i.e. their immunoreactivity, is
      not adversely affected by the drug conjugation procedure. We have described
      herein a measurement of the immunoreactivity of BR96-DOX, a conjugate comprised
      of BR96, a chimeric monoclonal antibody specific for the Le(y) tetrasaccharide
      commonly expressed on human carcinomas, and doxorubicin, an anticancer agent in
      widespread clinical use. We have employed a competitive RIA, in which microtiter
      wells were coated with synthetic Le(y) conjugated to human serum albumin and then
      incubated with 125I-labeled antibody BR96 in the presence of test conjugate or
      intact BR96 mAb. The test conjugates were found to compete as effectively as
      unconjugated BR96. This assay is highly applicable to QC processes with the intra
      assay CV = 2.0% and the interassay CV = 4.3%.

PMID- 1361154
TI  - The functional role of mesotelencephalic dopamine systems.

PMID- 1361155
TI  - Putative zinc finger protein encoded by a conserved chloroplast gene is very
      likely a subunit of a biotin-dependent carboxylase.

PMID- 1361156
TI  - A cdc2 gene of Petunia hybrida is differentially expressed in leaves, protoplasts
      and during various cell cycle phases.
AB  - Analysis of p34cdc2 kinase in higher eukaryotes has demonstrated that p34cdc2
      function is conserved in all eukaryotic cells. The p34cdc2 kinase (the product of
      the cdc2 gene) is required during the G1 cell cycle phase at the initiation of
      DNA replication and also in G2-M phases for entry into mitosis. In this paper we
      report the isolation and characterization of a cdc2 Petunia hybrida PCR fragment
      (cdc2Pet). Using a DNA probe based on this fragment and a p34cdc2-specific
      antibody, cdc2Pet transcript and p34 protein levels were found to be constant
      both in 2C nuclei of highly proliferating mesophyll 2C cells derived from
      protoplasts and in 2C nuclei isolated directly from expanded petunia leaves. Both
      the cdc2Pet transcript and p34cdc2 protein levels were found to be higher in
      nuclei at 4C than in those at 2C, even when these 4C nuclei were from non
      proliferating tissue. Thus cdc2Pet mRNA and protein levels measured in different
      tissues should not be interpreted to reflect exclusively the proliferative state
      of the tissue but also the frequency of G2 cells including those in the
      differentiated state.

PMID- 1361157
TI  - Quantitative determination of CGS 18102A, a new anxiolytic, in human plasma using
      capillary gas chromatography/mass spectrometry.
AB  - CGS 18102A is a novel hexahydrobenzopyranopyridine that has a mixed
      pharmacological profile of 5-HT-1A agonist and 5-HT-2 antagonist properties.
      Based upon these mechanisms, the compound is predicted to have anxiolytic
      efficacy with possible efficacy in depression. Preclinical studies in the rat
      have shown the drug to be well absorbed and extensively metabolized. Because of
      the anticipated low plasma levels in humans a gas chromatography/mass
      spectrometry (GC/MS) analytical method has been developed and validated to
      determine plasma concentrations of CGS 18102A in early clinical studies. The
      method utilizes CGS 18416A as the internal standard. Samples (1 mL) were
      extracted with pentane:ethyl acetate (75:25, v:v). Extracts were then
      concentrated and analysed directly by GC/MS. Separation was accomplished on a
      methylsilicone capillary column (30 m x 0.32 mm i.d.). GC/MS was carried out
      under positive ion ammonia CI conditions, with selected ion monitoring of the [M
      + H]+ ions (m/z = 262 and 248) for CGS 18102A and CGS 18416A, respectively. The
      method was successively applied to the analysis of clinical samples from an
      ascending multidose safety and tolerability study conducted in six normal healthy
      male volunteers.

PMID- 1361159
TI  - Ninth Annual ECP Symposium: public education on diet and cancer, Madrid, 17-19
      October 1991.

PMID- 1361158
TI  - Neuroleptic sensitivity in dementia with cortical Lewy bodies.

PMID- 1361160
TI  - Ovariectomy promotes the growth of altered hepatic foci after withdrawal and
      reintroduction of phenobarbital during hepatocarcinogenesis in rats.
AB  - Female F344/N rats were given 70% partial hepatectomies and intubated with
      diethyl-nitrosamine (DEN, 10 mg/kg) 24 hours later. They were fed a cereal-based
      diet, NIH-07 (NIH) + 0.05% phenobarbital (PB) for 6 months, at which time NIH +
      PB was withdrawn and the rats were ovariectomized (OV) or sham-operated (SH).
      Groups of 7-10 rats were fed a semipurified diet (AIN-76) for 1 or 2 months after
      withdrawal of NIH + PB, or NIH + PB for 2 months, or AIN-76 diet for 1 month and
      subsequently NIH + PB for 1 month. Placental glutathione S-transferase (PGST)-
      and gamma-glutamyltransferase (GGT)-positive (+) altered hepatic foci (AHF) were
      analysed by quantitative stereology. Ovariectomy stimulated growth of AHF after
      withdrawal and reintroduction of NIH + PB. AHF, especially PGST+ AHF, continued
      to regress throughout the PB withdrawal period in rats fed AIN-76 diet. In most
      studies of chemical hepatocarcinogenesis, females have been shown to develop a
      greater volume of AHF than males. In our study, however, ovariectomy stimulated
      the growth of AHF after withdrawal and reintroduction of PB. Because AHF
      occurring spontaneously in male rats develop more rapidly than in female rats,
      the greater rate of growth of AHF in OV female rats may reflect a similar
      mechanism.

PMID- 1361161
TI  - Isolation and characterization of equinatoxins from the sea anemone Actinia
      equina L.
AB  - Equinatoxins were purified from the tentacles and bodies of the sea anemone
      Actinia equina by the use of acetone precipitation, as well as column
      chromatographies on Sephadex G-50 and CM-cellulose according to the modified
      method of Macek and Lebez (1988). The equinatoxins obtained, equinatoxin 1 and 2,
      were hemolytic glycoproteins with a relative molecular mass of 20000. Equinatoxin
      2 was found to be rich in glycine, alanine and valine. The amino acid sequences
      of equinatoxins 1 and 2 were partially determined. A portion of the N-terminal
      amino acid sequence of equinatoxin 2 was similar to those of pyruvate kinase and
      sialidase.

PMID- 1361163
TI  - Cross-resistance of drug-resistant murine P388 leukemias to taxol in vivo.
AB  - The antimicrotubule agent taxol (NSC 125973) has shown clinical antitumor
      activity against several classically refractory tumors. We developed a drug
      resistance profile for taxol using ten drug-resistant P388 leukemias to identify
      potentially useful guides for patient selection for further clinical trials of
      taxol and possible non-cross-resistant drug combinations with taxol. Multidrug
      resistant P388 leukemias exhibited either clear (leukemia resistant to amsacrine)
      or marginal cross-resistance (leukemias resistant to doxorubicin, actinomycin D,
      and mitoxantrone) to taxol. Leukemias resistant to vincristine (non-multidrug
      resistant leukemia), camptothecin, melphalan, cisplatin, 1-beta-D
      arabinofuranosylcytosine, and methotrexate were not cross-resistant to taxol. The
      data suggest that (1) it may be important to exclude or to monitor with extra
      care patients who have previously been treated with amsacrine, doxorubicin,
      actinomycin D, or mitoxantrone and (2) a combination of one of the non-cross
      resistant drugs and taxol might exhibit therapeutic synergism.

PMID- 1361162
TI  - Fading responses in the evoked EMG after rocuronium in cats.
AB  - This study was performed to evaluate the inhibitory effect on motor nerve
      terminals by rocuronium using recovery curves of muscle compound action
      potentials (CAPs) and train-of-four ratios (TOFRs) in anaesthetized cats, and to
      compare the results with other relaxants reported previously. Recovery curves
      were derived from the amplitude of the CAP induced in the gastrocnemius muscle by
      the second of a paired stimulus (test response) to the sciatic nerve and compared
      with results evoked by the first component (conditioning response). The interval
      between the paired stimuli was increased stepwise from 7 to 1,000 msec, and the
      differences in amplitude of the test and conditioning responses were plotted on a
      graph by relating the changes in paired intervals. The recovery curve after
      rocuronium was less inhibited than after pancuronium, (100.4 +/- 5.9%, 82.3 +/-
      6.7% and 68.5 +/- 6.7% at 60, 100 and 500 msec intervals, compared with 70.3 +/-
      3.3%, 59.0 +/- 4.7% and 46.7 +/- 4.3% after pancuronium (P < 0.05). The recovery
      curves with d-tubocurarine were more depressed than with pancuronium; however,
      the RC with vecuronium was similar to that of rocuronium. The degree of fade in
      TOF by rocuronium was also less than those seen with d-tubocurarine and
      pancuronium. The results obtained suggest that rocuronium has less inhibitory
      effect on motor nerve terminals than do d-tubocurarine and pancuronium, and has a
      similar effect to that of vecuronium.

PMID- 1361164
TI  - FDA approves treatment IND protocol for taxol.

PMID- 1361165
TI  - Glutamate in the inferior colliculus plays a critical role in audiogenic seizure
      initiation.
AB  - Alterations of excitant amino acid (EAA) action are implicated in seizure
      susceptibility in the genetically epilepsy-prone rat (GEPR). The inferior
      colliculus (IC) is critical for audiogenic seizure (AGS) initiation in the GEPR.
      The present study observed that bilateral microinjection into the IC of L
      canaline, a glutamate synthesis inhibitor, decreased AGS severity in the GEPR and
      also decreased potassium-evoked release of glutamate from IC slices. Bilateral
      microinjection of NMDA receptor antagonists, 2-amino-7-phosphonoheptanoate (AP7)
      or 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) into IC blocked
      AGS, and an antagonist at non-NMDA EAA receptors, 6-cyano-7-nitroquinoxaline-2,3
      dione (CNQX), also blocked AGS. NMDA receptor antagonists were 5-200 times more
      effective than CNQX. Microinjection of a non-competitive NMDA receptor
      antagonist, dizocilpine (MK-801), into IC had little effect except with very high
      doses. Microinjection of CPP or AP7 into the IC blocked AGS at considerably lower
      doses as compared to pontine reticular formation (PRF). However, MK-801
      attenuated AGS when microinjected into PRF at doses that were ineffective in IC.
      Systemically administered CPP blocked AGS and significantly reduced IC neuronal
      firing in the behaving GEPR, suggesting an important action of systemically
      administered NMDA receptor antagonists on brainstem auditory nuclei critical to
      AGS. The present results support a critical role for glutamate acting, in part,
      through NMDA receptors in IC in initiation of AGS.

PMID- 1361166
TI  - GLOBOSA: a homeotic gene which interacts with DEFICIENS in the control of
      Antirrhinum floral organogenesis.
AB  - GLOBOSA (GLO) is a homeotic gene whose mutants show sepaloid petals and
      carpelloid stamens. The similarity of Glo mutants to those of the DEFICIENS
      (DEFA) gene suggests that the two genes have comparable functions in floral
      morphogenesis. The GLO cDNA has been cloned by virtue of its homology to the MADS
      box, a conserved DNA-binding domain also contained in the DEFA gene. We have
      determined the structure of the wild type GLO gene as well as of several glo
      mutant alleles which contain transposable element insertions responsible for
      somatic and germinal instability of Glo mutants. Analyses of the temporal and
      spatial expression patterns of the DEFA and GLO genes during development of wild
      type flowers and in flowers of various stable and unstable defA and glo alleles
      indicate independent induction of DEFA and GLO transcription. In contrast, organ
      specific up-regulation of the two genes in petals and stamens depends on
      expression of both DEFA and GLO. In vitro DNA-binding studies were used to
      demonstrate that the DEFA and GLO proteins specifically bind, as a heterodimer,
      to motifs in the promoters of both genes. A model is presented which proposes
      both combinatorial and cross-regulatory interactions between the DEFA and GLO
      genes during petal and stamen organogenesis in the second and third whorls of the
      flower. The function of the two genes controlling determinate growth of the
      floral meristem is also discussed.

PMID- 1361167
TI  - A novel homo-oligomeric protein responsible for an MPF-dependent microtubule
      severing activity.
AB  - An activity that severs stable microtubules has previously been detected in M
      phase extracts, but not in interphase extracts, of Xenopus eggs. We show that
      incubation of interphase extracts with purified MPF rapidly increases the
      microtubule-severing activity. We then report the identification and purification
      of a novel protein factor responsible for this MPF-dependent microtubule-severing
      activity. The purified microtubule-severing factor is a homo-oligomeric protein
      composed of 56 kDa polypeptide subunits. These subunits appear to assemble into a
      pentagonal loop, forming a doughnut-shaped molecule whose overall contours
      resemble a flattened ball. The microtubule-severing activity of the purified
      factor does not require ATP or divalent cations, and is inhibited by monomeric
      tubulin. The purified factor is capable of binding to both monomeric tubulin and
      microtubules. This factor is thus a novel kind of microtubule-binding protein in
      both structure and function, and may play an important role in the cell cycle
      dependent change in microtubule organization.

PMID- 1361168
TI  - Interactive surface in the PapD chaperone cleft is conserved in pilus chaperone
      superfamily and essential in subunit recognition and assembly.
AB  - The assembly of adhesive pili in Gram-negative bacteria is modulated by
      specialized periplasmic chaperone systems. PapD is the prototype member of the
      superfamily of periplasmic pilus chaperones. Previously, the alignment of
      chaperone sequences superimposed on the three dimensional structure of PapD
      revealed the presence of invariant, conserved and variable amino acids.
      Representative residues that protruded into the PapD cleft were targeted for site
      directed mutagenesis to investigate the pilus protein binding site of the
      chaperone. The ability of PapD to bind to fiber-forming pilus subunit proteins to
      prevent their participation in misassembly interactions depended on the
      invariant, solvent-exposed arginine-8 (R8) cleft residue. This residue was also
      essential for the interaction between PapD and a minor pilus adaptor protein. A
      mutation in the conserved methionine-172 (M172) cleft residue abolished PapD
      function when this mutant protein was expressed below a critical threshold level.
      In contrast, radical changes in the variable residue glutamic acid-167 (E167) had
      little or no effect on PapD function. These studies provide the first molecular
      details of how a periplasmic pilus chaperone binds to nascently translocated
      pilus subunits to guide their assembly into adhesive pili.

PMID- 1361169
TI  - Chaperonin-mediated protein folding: GroES binds to one end of the GroEL
      cylinder, which accommodates the protein substrate within its central cavity.
AB  - The mechanism of GroEL (chaperonin)-mediated protein folding is only partially
      understood. We have analysed structural and functional properties of the
      interaction between GroEL and the co-chaperonin GroES. The stoichiometry of the
      GroEL 14mer and the GroES 7mer in the functional holo-chaperonin is 1:1. GroES
      protects half of the GroEL subunits from proteolytic truncation of the
      approximately 50 C-terminal residues. Removal of this region results in an
      inhibition of the GroEL ATPase, mimicking the effect of GroES on full-length
      GroEL. Image analysis of electron micrographs revealed that GroES binding
      triggers conspicuous conformational changes both in the GroES adjacent end and at
      the opposite end of the GroEL cylinder. This apparently prohibits the association
      of a second GroES oligomer. Addition of denatured polypeptide leads to the
      appearance of irregularly shaped, stain-excluding masses within the GroEL double
      ring, which are larger with bound alcohol oxidase (75 kDa) than with rhodanese
      (35 kDa). We conclude that the functional complex of GroEL and GroES is
      characterized by asymmetrical binding of GroES to one end of the GroEL cylinder
      and suggest that binding of the substrate protein occurs within the central
      cavity of GroEL.

PMID- 1361170
TI  - Function in protein folding of TRiC, a cytosolic ring complex containing TCP-1
      and structurally related subunits.
AB  - T-complex polypeptide 1 (TCP-1) was analyzed as a potential chaperonin
      (GroEL/Hsp60) equivalent of the eukaryotic cytosol. We found TCP-1 to be part of
      a hetero-oligomeric 970 kDa complex containing several structurally related
      subunits of 52-65 kDa. These members of a new protein family are assembled into a
      TCP-1 ring complex (TRiC) which resembles the GroEL double ring. The main
      function of TRiC appears to be in chaperoning monomeric protein folding: TRiC
      binds unfolded polypeptides, thereby preventing their aggregation, and mediates
      the ATP-dependent renaturation of unfolded firefly luciferase and tubulin. At
      least in vitro, TRiC appears to function independently of a small co-chaperonin
      protein such as GroES. Folding of luciferase is mediated by TRiC but not by
      GroEL/ES. This suggests that the range of substrate proteins interacting
      productively with TRiC may differ from that of GroEL. We propose that TRiC
      mediates the folding of cytosolic proteins by a mechanism distinct from that of
      the chaperonins in specific aspects.

PMID- 1361171
TI  - Regulation of the mec-3 gene by the C.elegans homeoproteins UNC-86 and MEC-3.
AB  - The mec-3 gene encodes a homeodomain protein with LIM repeats that is required
      for the specification of touch cell fate in Caenorhabditis elegans. Previous
      experiments suggested that mec-3 expression requires the product of the unc-86
      gene, a POU-type homeoprotein, and mec-3 itself. We have analyzed the control of
      mec-3 expression by identifying potential cis regulatory elements in the mec-3
      gene (by conservation in a related nematode and by DNase I footprinting using unc
      86 and mec-3 proteins) and testing their importance by transforming C.elegans
      with mec-3lacZ fusions in which these sites have been mutagenized in vitro. Both
      unc-86 and mec-3 proteins bind specifically to the promoter of the mec-3 gene,
      suggesting that both proteins may be directly involved in the regulation of the
      mec-3 gene. In addition, the footprint pattern with mec-3 protein is altered in
      the presence of unc-86 protein. In vivo transformation experiments reveal that
      some of the binding regions of the two proteins are needed for general positive
      control and maintenance of mec-3 expression while others have no detectable,
      unique function. Interestingly, the unc-86 gene appears to be required not only
      to initiate mec-3 expression but also to maintain it.

PMID- 1361172
TI  - The DNA binding specificity of the bipartite POU domain and its subdomains.
AB  - The POU domain is a conserved DNA binding region of approximately 160 amino acids
      present in a family of eukaryotic transcription factors that play regulatory
      roles in development. The POU domain consists of two subdomains, the POU-specific
      (POUS) domain and a POU-type homeodomain (POUHD). We show here that, like the
      POUHD, the Oct-1 POUS domain can bind autonomously to DNA but with low affinity.
      DNA binding studies and in vitro binding site selection revealed that the POU
      subdomains each have a different sequence specificity. The binding consensus of
      the POUS domain [gAATAT(G/T)CA] and POUHD (RTAATNA) respectively overlap the
      'left half' and right half' of the POU domain recognition sequence
      [a(a/t)TATGC(A/T) AAT(t/a)t]. In addition to the core sequence, which is very
      similar to the octamer motif (ATGCAAAT), the flanking bases make a significant
      contribution to the binding affinity of the POU domain. Interestingly, at some
      positions the sequence preferences of the isolated POU subdomains are distinct
      from those of the POU domain, suggesting that the POU domain binding site is more
      than a simple juxtaposition of the POUS and POUHD target sequences. In addition,
      analysis of the binding kinetics of the POU domain and POUHD indicates that the
      POUS domain enhances the binding affinity by reducing the dissociation rate. Our
      results show that the POU domain proteins have DNA binding properties distinct
      from those of classic homeodomain proteins. We suggest a model for the way in
      which an additional conserved domain adds further specificity to DNA recognition
      by homeodomain proteins.

PMID- 1361174
TI  - Electrophysiological and electropharmacological studies in pre-excitation
      syndromes: results with propafenone therapy and isoproterenol infusion testing.
AB  - To study the electrophysiological effects of oral propafenone on accessory
      pathways and determine the potential for catecholamine-mediated reversal of these
      effects, comprehensive electrophysiology studies (EPS) were conducted in 11
      patients with manifest (n = 9) or concealed (n = 2) pre-excitation syndrome. EPS
      were performed at baseline (in the drug-free state), after oral propafenone
      loading, and with isoproterenol infusion during propafenone therapy. The study
      group included 10 men and 1 woman with a mean age of 39 +/- 13 years, who
      presented with symptoms of palpitations (n = 6), presyncope (n = 3) and syncope
      (n = 2). The clinical arrhythmia was atrioventricular reciprocating tachycardia
      (n = 6), atrial flutter/fibrillation (n = 3), or both (n = 2). During the
      baseline EPS the accessory pathway location was identified as left (n = 6) or
      septal (n = 5). The mean anterograde effective refractory period was 265 +/- 42
      ms, the shortest pre-excited RR interval 259 +/- 20 ms and the retrograde
      refractory period 258 +/- 39 ms. Orthodromic atrioventricular reciprocating
      tachycardia was induced in 10 patients (mean cycle length = 324 +/- 31 ms).
      Antidromic reciprocating tachycardia was induced in one patient (cycle length =
      340 ms). In all the 11 patients EPS were repeated after 4 days of oral
      propafenone loading (668 +/- 226 mg daily) when drug steady state was expected to
      have been achieved. One additional patient had baseline EPS but developed
      clinical arrhythmia recurrences after propafenone loading and thus he was
      excluded from the study; follow-up EPS were conducted on procainamide.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1361173
TI  - Isolation and analysis of the fission yeast gene encoding polymerase delta
      accessory protein PCNA.
AB  - Five monoclonal antibodies raised against rat PCNA cross-reacted with a similar
      protein in the fission yeast Schizosaccharomyces pombe. One of these was used to
      screen an S.pombe cDNA expression library. An incomplete cDNA was isolated and
      used to screen a genomic library, identifying a single gene, designated pcn1+
      (proliferating cell nuclear antigen). The gene encodes a protein of 260 amino
      acids, with a deduced sequence 52% identical to human and rat PCNAs, which are
      98.5% identical to each other. The budding yeast PCNA homologue POL30 is only 35%
      identical to the human and rat proteins. Pcn1 has a region near the C-terminus of
      particularly high homology to higher eukaryotic PCNA proteins. pcn1+ is essential
      for viability and delta pcn1 cells undergo aberrant DNA replication before cell
      cycle arrest. Overproduction of the protein leads to cell cycle delay in G2.
      Disruption of pcn1+ is complemented by the human PCNA gene, demonstrating that
      these genes are functional homologues.

PMID- 1361175
TI  - Differentiation of beta-blocker effects on serum lipids and apolipoproteins in
      hypertensive patients with normolipidaemic or dyslipidaemic profiles.
AB  - To evaluate the differential effects of beta-blockers on serum lipids and
      apolipoproteins in normolipidaemic and dyslipidaemic hypertensives, 330 patients
      with mild to moderate essential hypertension were studied 1 month after placebo
      therapy and 6 months after monotherapy with propranolol (n = 53), atenolol (n =
      66), metoprolol (n = 58), pindolol (n = 53), or celiprolol (n = 100). Serum total
      cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C), low
      density lipoprotein-cholesterol (LDL-C), and apolipoproteins (Apo) A1 and B were
      measured at baseline and study end. A total of 136 (41.2%) patients were
      considered normolipidaemic (pretreatment LDL-C < 160 mg.dl-1) and 194 (58.8%)
      were considered dyslipidaemic (LDL-C > 160 mg.dl-1). Changes in total cholesterol
      differed between normolipidaemics and dyslipidaemics with propranolol (+13% in
      normolipidaemics vs -0.5% in dyslipidaemics, P < 0.001), atenolol (+7% vs -2%, P
      = 0.01), metoprolol (+9% vs -4%, P0.0006), pindolol (+8% vs -9%, P < 0.001), and
      celiprolol (-1% vs -13%, P = 0.002). HDL-C differed less, with propranolol (-18%
      vs -13%), atenolol (-6% vs -2%), metoprolol (-2% vs -6%), pindolol (+4% vs +1%),
      and celiprolol (+9% vs +4%); none of these changes between normolipidaemic and
      dyslipidaemic patients were statistically significant. LDL-C changes differed the
      most, with propranolol (+35% vs -1%, P < 0.0001), atenolol (+15% vs -4%, P =
      0.001), metoprolol (+12% vs -6%, P = 0.004), pindolol (+12% vs -13%, P < 0.0001),
      and celiprolol (+3% vs -16%, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361176
TI  - [A novel function of tetrahydrobiopterin].
AB  - 6R-L-erythro-5, 6, 7, 8-Tetrahydrobiopterin (6R-BH4) is known as a cofactor for
      the hydroxylases of phenylalanine, tyrosine and tryptophan and also as a cofactor
      for nitric oxide synthase. Recently, a novel function of 6R-BH4 has been found:
      that is, 6R-BH4 acts on specific membrane receptors to directly stimulate the
      release of monamine neurotransmitters such as dopamine and serotonin,
      independently of its cofactor activity. In addition, it indirectly stimulates the
      release of non-monoamine neurotransmitters such as acetylcholine and glutamate,
      through activation of monoaminergic systems. In this paper, we briefly review
      recent experimental data, which provide new insights into the role of 6R-BH4 as a
      regulator of neuronal function. We also discuss the possibility of treatment by
      6R-BH4 of neuropsychiatric diseases such as Parkinson's disease, Alzheimer's
      disease, depression and infantile autism.

PMID- 1361177
TI  - [Effects of M6434, an orally active alpha 1-adrenoceptor agonist, on experimental
      postural hypotension in rabbits and dogs].
AB  - We examined the effects of M6434 on mean blood pressure and heart rate in
      conscious rabbits and dogs and on experimental models of postural hypotension in
      conscious rabbits and anesthetized dogs. M6434, given orally, elevated the mean
      blood pressure in conscious rabbits and dogs. The pressor effect of M6434 was
      more potent than that of midodrine, but the bradycardiac action of M6434 was
      weaker than that of midodrine. M6434 (1.0 and 3.0 mg/kg, p.o.) prevented the head
      up tilt-induced reductions of mean blood pressure and cerebral tissue blood flow
      in conscious rabbits, and these effects of M6434 were about 3 times more potent
      than those of midodrine. In the postural hypotension of anesthetized dogs, M6434
      at the doses more than 10 micrograms/kg, i.v. also produced the preventive
      effects on mean blood pressure and cerebral tissue blood flow. These effects of
      M6434 were about 10-30 times more potent than those of midodrine. These results
      show that M6434 possesses a potent hypertensive effect with a weaker bradycardiac
      action and suggest that M6434 may be a potential candidate for an anti
      hypotensive agent that can prevent the deterioration of hemodynamics in postural
      hypotension.

PMID- 1361178
TI  - [Gastritis, feeling of fullness and stomach irritability. Antacids as first
      choice therapy. Conference on Traditional Therapy for Classical Epigastric
      Symptoms: Renaissance of Antacids? Athens, 28 September 1992].

PMID- 1361179
TI  - Anti-CD4 monoclonal antibodies in therapy: creation of nonclassical tolerance in
      the adult.

PMID- 1361180
TI  - Comparative biochemical, morphological, and immunocytochemical studies between C
      6 glial cells of early and late passages and advanced passages of glial cells
      derived from aged mouse cerebral hemispheres.
AB  - We have used C6 glial cells (2B clone), early and late passage, as well as
      advanced passages (8-17) of glial cells derived from aged (18-month-old) mouse
      cerebral hemispheres (MACH), as model systems for studying glial properties. In
      this study passages 20-24 were considered "early" and passages 73-90 were
      considered "late." Activities of glutamine synthetase (GS) and cyclic nucleotide
      phosphohydrolase (CNP) were used as biochemical markers for astrocytes and
      oligodendrocytes, respectively. Glial phenotypes were identified
      immunocytochemically using double staining for glial fibrillary acidic protein
      (GFAP) and A2B5 antigen (type 1 and type 2 astrocytes) or galactocerebroside
      (GalC) and A2B5 antigen (oligodendrocytes); cells positive for A2B5 and negative
      for both GFAP and GalC were considered to be precursor cells. Cultures were grown
      either in DMEM supplemented with 10% fetal bovine serum or in serum-free
      chemically defined medium (CDM) supplemented with insulin and transferrin. We
      report that early-passage C6 glial cells continue to be bipotential cells and
      when grown in the absence of serum express high GS and CNP activities correlating
      with the high number of GFAP- and GalC-positive cells, respectively. Late-passage
      cells continued to be committed to the type 2 astrocytic phenotype regardless of
      media composition (+/- serum). MACH cultures consist of protoplasmic type 1
      astrocytes, differentiated type 2 astrocytes, and oligodendrocytes as well as
      glial progenitor cells. When these cultures were grown in CDM+transferrin, both
      GS and CNP activities increased, suggesting that transferrin has provided the
      signal for progenitor cells present in these cultures derived from aged brain to
      differentiate into type 2 astrocytes and oligodendrocytes.

PMID- 1361181
TI  - [The electromotor unit of the upper urinary tract].
AB  - The muscular architecture of the upper urinary tract constitutes a functional but
      no anatomical syncytium, where the cells are coupled by nexus and crosslinking
      with low electrical resistance. The action potentials are evoked by spontaneous
      depolarisation of muscle cells. The sites of peak depolarisation could be termed
      pace-maker cells. They are localized in the calices. Recent studies have,
      however, described myofilaments capable of contraction in the proximal tubuli
      already. Volume and pressure loads on the hollow system have been identified as
      the regulation mechanism. Modulatory function is directly related to evidence of
      alpha- and beta-adrenergic receptors, of receptor subtypes, of the adenylate
      cyclase system, of histamine- and possibly prostaglandin- and serotonin-receptors
      as well.

PMID- 1361182
TI  - Intense sound increases the level of an unidentified amine found in perilymph.
AB  - The hypothesis tested was that intense sound increases the levels of a substance
      such as glutamate, a putative neurotransmitter and neurotoxic substance, in the
      perilymph compartment of the cochlea. Artificial perilymph was perfused through
      the perilymphatic compartment of the guinea pig cochlea and the effluent
      collected during successive 10-min periods. The effects of perfusing an
      artificial perilymph containing normal levels of Na+ (NARP) were compared to the
      effects of perfusing an artificial perilymph containing very low concentrations
      of Na+ (VLNa). The effluent was collected during ambient noise and during
      increasing intensities of broad-band noise (10 min at 106, 112, 118 and 124 dB
      SPL). Levels of amines in the effluent were measured by HPLC utilizing precolumn
      o-phthalaldehyde (OPA) derivatization and fluorescence detection. VLNa increased
      the levels of glutamate and several other amines in effluent from the cochlea
      compared to levels obtained in NARP. Compared with its level during ambient room
      noise, the concentration of an unidentified amine labeled Unk 2.5 increased
      during intense noise (124 dB SPL). Intense noise induced no detectable changes in
      the concentrations of glutamate and fifteen other amines. The chemical identity
      and role of Unk 2.5 remain to be determined.

PMID- 1361183
TI  - Evidence for L-glutamate release in frog vestibular organs.
AB  - The present study was devised in order to ascertain whether L-glutamate (Glu) is
      the neurotransmitter at the primary afferent synapse in frog vestibular organs.
      To this end different groups of frog isolated semicircular canals were stimulated
      by means of solutions slightly enriched in K+ (5 mM K(+)-rich solutions are
      sufficient to produce a strong, long-lasting, transmitter release from the basal
      pole of sensory cells) both in normal conditions and after low-Ca(2+)-high-Mg2+
      impairment of the synaptic transmission. The concentration of Glu in the
      surrounding medium, determined by means of a bioluminescence-enzymatic method,
      was evaluated in two different experimental conditions: a) when the canals (5
      canals placed inside little net bags) were immersed in a 5 mM K(+)-stimulating
      solution; b) during the superfusion of the canals (25 canals placed into a little
      perfusion chamber) with a 5 mM K(+)-stimulating solution. The net bag experiments
      demonstrated that K(+)-rich solutions can provoke an outflow of Glu from canal
      organs only if the crista ampullaris is present and functioning. Glu fluctuations
      were in fact suppressed by employing canals deprived of the ampulla or after low
      Ca2(+)-high-Mg2+ synaptic blockade. The superfusion experiments demonstrated that
      the time course of 5 mM K(+)-induced release of Glu from the sensory organ
      strictly parallels the time course of 5 mM K(+)-induced EPSPs and spike discharge
      in afferent axons. These results strongly support the hypothesis that Glu is, or
      is released with, the afferent transmitter in frog inner ear sensory organs.

PMID- 1361184
TI  - Immunochemical localization of a region of chaperonin-60 important for productive
      interaction with chaperonin-10.
AB  - An IgG1 monoclonal antibody (mAb 54G8) which binds to both Bordetella pertussis
      chaperonin-60 (cpn60) and Escherichia coli cpn60 (GroEL) was produced. mAb 54G8
      as well as Fab fragments prepared from this antibody were found to abolish the
      ability of chaperonin-10 (cpn10, GroES) to inhibit the ATPase activity of both B.
      pertussis cpn60 and E. coli cpn60. Electron microscopy was used to localize the
      binding site of the monoclonal antibody on the B. pertussis cpn60 molecule. In
      the absence of the antibody, the B. pertussis molecule exhibited the
      tetradecameric structure typical of cpn60. Both end views (showing 7-fold
      symmetry of the face of the molecule) and side views were evident. When mAb 54G8
      was bound, B. pertussis cpn60 molecules appeared to be cross-linked so that they
      formed long chains. Only side views of the molecules were seen in these long
      chains. When B. pertussis cpn60 complexed with Fab fragments of mAb 54G8 was
      examined, chains were no longer observed. Instead, side views of B. pertussis
      cpn60 were often seen with Fab fragments extending from the ends of the molecule.
      These data indicate that mAb 54G8 appears to bind at or near the end of the B.
      pertussis cpn60 molecule and that binding of mAb 54G8 at this location affects
      the ability of cpn10 to productively interact with cpn60, most likely either by
      sterically blocking the binding of cpn10, by affecting the conformation of cpn60
      in such a way that it no longer binds cpn10, or by inhibiting proper transduction
      of the effects of cpn10 binding.

PMID- 1361185
TI  - An involucrin-like protein in hepatocytes serves as a substrate for tissue
      transglutaminase during apoptosis.
AB  - Cornified envelopes and apoptotic bodies are transglutaminase-cross-linked end
      products of physiological cell death pathways. The two structures have similar
      amino acid composition. Involucrin has been considered as a cornified envelope
      precursor protein expressed specifically in terminally differentiating
      keratinocytes and squamous epithelia. We report the presence in hepatocytes of an
      involucrin-like protein which could be purified from dog liver with procedures
      characteristic to involucrins. When compared to purified dog esophagus
      involucrin, the liver protein also reacts with anti-involucrin antibodies, has
      the same relative molecular mass, possesses similar amino acid composition, and
      shows almost identical peptide mapping pattern. The involucrin-like protein is
      detectable by immunohistochemistry in normal and apoptotic hepatocytes, is a
      substrate of tissue transglutaminase, and is incorporated into cross-linked
      apoptotic bodies. These results suggest that there are overlapping molecular
      components in the two characteristic forms (cornification and apoptosis) of
      naturally occurring cell death.

PMID- 1361186
TI  - A newly synthesized protein interacts with GroES on the surface of chaperonin
      GroEL.
AB  - To facilitate folding and assembly of different proteins, chaperonin GroEL
      requires the presence of its helper protein GroES. Using a photochemical cross
      linking approach, we show that GroES and newly synthesized pre-beta-lactamase
      (pre-beta lac) contact with each other only within the ternary complex with
      GroEL. Possibly owing to this contact GroES is able to directly influence the pre
      beta lac/GroEL interaction. Furthermore, the cross-linking of pre-beta lac to
      GroES suggests that the binding of the protein ligands to GroEL occurs near the
      GroES binding site, known to be in the central hole space of GroEL.

PMID- 1361187
TI  - Effect of introducing different carboxylate-containing side chains at position 85
      on chromophore formation and proton transport in bacteriorhodopsin.
AB  - During the initial stages of the bacteriorhodopsin photocycle, a proton is
      transferred from the Schiff base to the deprotonated carboxylate of Asp85.
      Earlier studies have shown that replacement of Asp85 by Asn completely abolishes
      proton transport activity, whereas extension of the side chain by an additional
      carbon-carbon bond (Asp85-->Glu) results in a functional proton pump. Here we
      show that extension of the Asp85 side chain by two additional bond lengths also
      results in a functional proton pump as long as the terminal group is a
      carboxylate moiety. These side chains were created by modification of the
      cysteine residue in the Asp85-->Cys mutant with either iodoacetic acid or
      iodoacetamide. In vitro chromophore formation studies show that the rate of
      Schiff base protonation in mutants that contain a carboxylate at residue 85 is
      invariably faster than in mutants that contain neutral substitutions at this
      position. We conclude that in bacteriorhodopsin, there is considerable tolerance
      in the volume of the side chain that can be accommodated at position 85 and that
      the presence of a carboxylate at residue 85 is important both for proton pumping
      and for stabilizing the protonated Schiff base.

PMID- 1361188
TI  - Dopamine D2 receptor stimulation of Na+/H+ exchange assessed by quantification of
      extracellular acidification.
AB  - A microphysiometer was used to quantify the rate of extracellular acidification
      by C6 glioma cells and L fibroblasts expressing recombinant dopamine D2
      receptors. The dopamine D2 receptor agonist, quinpirole, accelerated the rate of
      acidification of the medium by C6 cells expressing either the short or long form
      of D2 receptors, D2(415) and D2(444), but not by wild-type cells that were not
      transfected with a D2 receptor cDNA. The rate of acidification increased with
      increasing concentrations of quinpirole up to 100 nM. Inhibition of the response
      by the dopamine D2 antagonist, spiperone, provided additional evidence that the
      enhanced extracellular acidification resulted from stimulation of D2 receptors.
      To test the hypothesis that D2 receptor-stimulated extracellular acidification
      was due to transport of protons by a Na+/H+ antiporter and reflected
      intracellular alkalinization, the effect of two inhibitors of Na+/H+ exchange,
      amiloride and methyl-isobutyl-amiloride, was determined. Both compounds inhibited
      quinpirole-induced extracellular acidification at concentrations that did not
      alter D2 receptor-mediated inhibition of adenylylcyclase or radioligand binding
      to D2 receptors. In addition, quinpirole-induced extracellular acidification was
      greatly inhibited by removal of sodium from the extracellular medium, confirming
      the participation of Na+/H+ exchange in the extrusion of acid. Quinpirole (100
      nM) also increased the rate of extracellular acidification by L cells expressing
      D2(415), LZR1 cells. Treatment with pertussis toxin (100 ng/ml for 18 h) had no
      effect on the quinpirole-induced acid extrusion by C6D2(415) and LZR1 cells,
      although the same pertussis toxin treatment regimen completely prevented
      inhibition of adenylylcyclase. We conclude that recombinant D2 receptors
      accelerate Na+/H+ exchange in C6 cells and L fibroblasts by a pathway that does
      not involve inhibition of adenylylcyclase or pertussis toxin-sensitive G
      proteins.

PMID- 1361189
TI  - Site-directed mutagenesis of tyrosine hydroxylase. Role of serine 40 in
      catalysis.
AB  - We have investigated the role of serine 40 (Ser-40) in tyrosine hydroxylase (TH)
      catalysis of basal and activated enzymes by protein kinase A (PKA)-mediated
      phosphorylation. Wild type and mutant TH were transiently and stably expressed in
      AtT-20 cells, and the enzymatic activities of the recombinant enzymes were
      analyzed. The specific enzymatic activity of transiently expressed TH mutants Ser
      40-->leucine or-->tyrosine (Leu-40m or Tyr-40m) was higher than that of the wild
      type enzyme or of other mutants in which Ser-8, -19, and -31 were replaced by
      leucine. The kinetic studies carried out with the stably expressed TH show that
      the Km for the cofactor 6-methyltetrahydropterine is lower and the Ki for
      dopamine is higher when the enzymatic hydroxylation is catalyzed by the Leu-40m
      or Tyr-40m than by the wild type enzyme. The kinetic parameters and the pH
      profile of the enzymatic hydroxylation catalyzed by the Leu-40m or Tyr-40m are
      similar to the enzyme activated by PKA-mediated phosphorylation. We suggest that
      Ser-40 in TH exerts an inhibitory influence on the enzymatic activity, and its
      replacement with another amino acid by site-directed mutagenesis or its
      modification by phosphorylation leads to a change in conformation with an
      increased enzymatic activity. The importance of Ser-40 in the activation of TH by
      PKA-mediated phosphorylation was investigated by comparing the activation of the
      wild type enzyme with that of Leu-40m or Tyr-40m. The findings that the enzymatic
      activity is increased by PKA-mediated phosphorylation of the wild type enzyme,
      but not of the Leu-40m or Tyr-40m, demonstrate that phosphorylation at Ser-40 is
      essential for activation of TH by PKA. The findings that addition of ATP plus
      cAMP to homogenates from transfected AtT-20 cells stimulates the recombinant wild
      type TH activity indicate that these cells contain endogenous cAMP-dependent
      protein kinase.

PMID- 1361191
TI  - Molecular cloning of a homeobox transcription factor from adult aortic smooth
      muscle.
AB  - We report here the cloning of a cDNA encoding a homeobox transcription factor
      from vascular smooth muscle and describe its unique pattern of mRNA expression at
      different stages in development. The cDNA isolated is 1576 base pairs in length
      not including the poly(A) tail and contains an open reading frame coding for a
      predicted 372-amino acid homeobox protein. During early embryogenesis, expression
      was detected in the neural tube with a sharp expression boundary occurring at an
      anterior position, in the myelencephalon, in the third and fourth branchial
      arches, and in vessels leading from the heart. In adults, however, transcripts
      were only detected in aortic smooth muscle and lung but were undetectable in
      cardiac or skeletal muscle, visceral smooth muscle, and many other tissues
      including brain. In neonates, expression was detected in the outflow tracts of
      the heart as well as in the cardiomyocytes. The expression pattern of this gene
      suggests that, although it likely has multiple roles during development, in the
      adult, it may participate in the control of vascular smooth muscle
      differentiation and proliferation.

PMID- 1361192
TI  - Issues and advances in the pharmacotherapy of asthma.
AB  - Evidence is accumulating that inflammation of the airways is directly responsible
      for the increased bronchial hyperresponsiveness (BHR) and lung function
      obstruction in asthma. Bronchoprovocation with non-specific, direct
      bronchoconstrictors (methacholine and/or histamine) can be used as an indirect
      measurement of inflammation. Thus bronchoprovocation is a useful method for
      evaluating the long-term benefits of various therapies in asthma. The focus of
      asthma therapy research is now on the development of anti-inflammatory agents.
      Inhaled corticosteroids are currently the most potent anti-inflammatory agents in
      the treatment of asthma and so are generally the most effective in reducing BHR
      with long-term use. Non-corticosteroid anti-inflammatory agents that are
      currently available are reviewed. Recent studies have suggested that regular use
      of inhaled bronchodilators may actually be detrimental in asthma. At this time
      the data is still inconclusive but certainly warrants the attention of
      practitioners and requires further research, particularly in relation to the long
      acting beta 2-agonists, formoterol and salmeterol.

PMID- 1361190
TI  - Impaired tetramer assembly of variant medium-chain acyl-coenzyme A dehydrogenase
      with a glutamate or aspartate substitution for lysine 304 causing instability of
      the protein.
AB  - Ninety percent of variant medium-chain acyl-CoA dehydrogenase (MCAD) alleles in
      patients with MCAD deficiency carry a 985 A-->G transition which causes glutamate
      substitution for lysine 329 in precursor (p) MCAD (K-304 in mature MCAD). We have
      used site-directed mutagenesis to produce three variant cDNAs encoding variant
      pMCAD with glutamate (Kp329E2), aspartate (Kp329D), or arginine (Kp329R)
      substitution for Kp329. We carried out in vitro expression of cDNAs, and
      incubated the translation products with isolated rat liver mitochondria. Kp329E
      was imported into mitochondria and processed into the mature subunit as
      efficiently as wild-type. Gel filtration analysis of the mitochondria revealed
      that at 10 min after import, markedly more K304E eluted as a monomer than did
      wild-type, and the amount of K304E tetramer formed was distinctly less than wild
      type at any point up to 60 min after import, indicating that the assembly of
      K304E is defective. After further incubation, K304E decayed more rapidly than did
      wild-type, indicating a reduced stability. In similar studies, K304R behaved like
      the wild-type, while K304D closely resembled K304E, indicating that the presence
      of a basic residue at 304 is essential for tetramer formation and
      intramitochondrial stability of mature MCAD.

PMID- 1361193
TI  - Thyroid stimulatory autoantibodies in different patients with autoimmune thyroid
      disease do not all recognize the same components of the human thyrotropin
      receptor: selective role of receptor amino acids Ser25-Glu30.
AB  - To study the interaction between TSH, autoantibodies and the amino-terminal half
      of the TSH receptor extracellular region (amino acids 1-260; domains ABC), we
      constructed 20 LH/CG chimeric receptor cDNAs. The prototypic receptor for
      modification contained domains ABC of the TSH receptor and domains DE of the
      LH/CG receptor. Segments (6-13 amino acids) within the ABC domains were replaced
      with the corresponding amino acids of the rat LH/CG receptor. Fifteen of the 20
      chimeric receptors could be expressed functionally in Chinese hamster ovary
      cells. Twelve retained both high affinity TSH binding and normal signal
      transduction. These 12 receptors were tested with a panel of 10 patients'
      immunoglobulin G (IgG) samples containing potent TSH receptor stimulatory
      activity. With 11 of the receptor variants, the cAMP responses were similar to
      those with the prototype receptor (TSH-LHR-6). However, the -A1 variant of TSH
      LHR-6 (Ser25-Glu30) responded poorly to 6 of 10 IgGs. The same pattern was
      observed when the IgGs were tested for their ability to inhibit [125I] TSH
      binding to the receptor variants, suggesting qualitative differences between the
      different stimulatory TSH receptor autoantibodies. Therefore, we examined the
      dose-response relationship of 2 IgGs that were approximately equipotent when
      tested with TSH-LHR-6 and its -A1 variant and another 2 IgGs that displayed
      greatly diminished potency with respect to the -A1 variant. Despite dilution to
      nearly undetectable levels, the relative potencies of the 4 IgG samples for both
      types of receptors remained similar. These data demonstrate directly that
      stimulatory TSH receptor autoantibodies do not all recognize the same components
      of the TSH receptor. The segment of the TSH receptor discriminated by these
      autoantibodies is between amino acids Ser25-Glu30.

PMID- 1361195
TI  - Alertness and attention: basic science and electrophysiologic correlates.
AB  - There has been much research in the electrophysiologic correlates of alertness
      and attention, but it is fragmented into many subfields. This article integrates
      current knowledge across multiple disciplines and methodologies to provide a
      broad overview of alertness and attention. First, terms that are related to
      alertness and attention are clarified. Then, there is a discussion of basic
      neuroscience, human neurophysiology, and clinical fields that impact on alertness
      and attention. Areas discussed include thalamic and neurotransmitter-specific
      ascending pathways. EEG, event-related potentials, and both physiologic and
      pathologic states of decreased alertness or attention.

PMID- 1361194
TI  - Binding assay for thyrotropin receptor autoantibodies using the recombinant
      receptor protein.
AB  - We have characterized a transfected Chinese hamster ovary cell line, JP09, which
      expresses high levels of the human TSH receptor (TSH-R). Based on a theoretical
      biological activity for TSH of 40 IU/mg, JP09 has approximately 90,000 receptors
      per cell, having a dissociation constant of 1.64 x 10(3) mU/L or 1.47 x 10(-9)
      mol/L. We have used JP09 to prepare solubilized TSH-Rs which have formed the
      basis of a binding assay for thyroid-binding inhibiting immunoglobulins in
      unfractionated sera. We have compared the JP09 assay with the TRAK assay (which
      is based on solubilized porcine TSH-R) and found a highly positive correlation
      between the two assays, r = 0.83 P < 0.0001, in 55 sera from patients with
      autoimmune thyroid disease. JP09 can be adapted to growth in suspension culture,
      permitting large scale production. The tracer in the assay is bovine [125I]TSH;
      surprisingly, despite the use of a hTSH-R, hTSH had no effect on the binding of
      the tracer up to 10(3) mU/L and only a minor effect at 10(4) mU/L.

PMID- 1361196
TI  - Familial apolipoprotein E deficiency and type III hyperlipoproteinemia due to a
      premature stop codon in the apolipoprotein E gene.
AB  - A kindred with apolipoprotein E deficiency and a truncated lower molecular weight
      apoE mutant, designated apoE-3Washington, has been identified. Gel
      electrophoresis demonstrated complete absence of the normal apoE isoproteins and
      the presence of a small quantity of a lower molecular weight apoE. Plasma apoE
      levels in the proband were approximately 4% of normal. This marked deficiency of
      apoE resulted in delayed uptake of chylomicron and very low density lipoprotein
      (VLDL) remnants by the liver, elevated plasma cholesterol levels, mild
      hypertriglyceridemia, and the development of type III hyperlipoproteinemia.
      Sequence analysis of the patient's apoE gene revealed a single nucleotide
      substitution of an A for a G, which converted amino acid 210 of the mature
      protein, tryptophan (TGG), to a premature chain termination codon (TAG), thus
      leading to the synthesis of a truncated E apolipoprotein of 209 amino acids with
      a molecular mass of 23.88 kDa. Northern blot analysis of differentiated monocyte
      derived macrophages demonstrated a mutant mRNA indistinguishable in size from
      normal apoE mRNA. The nucleotide substitution also resulted in the formation of a
      new restriction site for Mae I. Using this enzyme we were able to establish that
      the proband is a homozygote and that her two offsprings are heterozygous for the
      epsilon-3Washington allele. These data demonstrate that the striking deficiency
      of apoE-3Washington results in a moderate form of type III hyperlipoproteinemia.
      The clinical presentation also suggests a dispensable role of apoE in the nervous
      system and in immunoregulation.

PMID- 1361197
TI  - Cellular bases of neocortical activation: modulation of neural oscillations by
      the nucleus basalis and endogenous acetylcholine.
AB  - In the mammalian neocortex, the EEG reflects the state of behavioral arousal. The
      EEG undergoes a transformation, known as activation, during the transition from
      sleep to waking. Abundant evidence indicates the involvement of the
      neurotransmitter acetylcholine (ACh) in EEG activation; however, the cellular
      basis of this involvement remains unclear. We have used electrophysiological
      techniques with in vivo and in vitro preparations to demonstrate actions of
      endogenous ACh on neurons in auditory neocortex. In vivo stimulation of the
      nucleus basalis (NB), a primary source of neocortical ACh, (1) elicited EEG
      activation via cortical muscarinic receptors, (2) depolarized cortical neurons,
      and (3) produced a change in subthreshold membrane potential fluctuations from
      large-amplitude, slow (1-5 Hz) oscillations to low-amplitude, fast (20-40 Hz)
      oscillations. The NB-mediated change in pattern of membrane potential
      fluctuations resulted in a shift of spike discharge pattern from phasic to tonic.
      Stimulation of afferents in the in vitro neocortex elicited cholinergic actions
      on putative layer 5 pyramidal neurons. Acting via muscarinic receptors,
      endogenous ACh (1) reduced slow, rhythmic burst discharge and facilitated higher
      frequency, single-spike discharge in burst-generating neurons, and (2)
      facilitated the appearance and magnitude of intrinsic membrane potential
      oscillations. These in vivo and in vitro observations suggest that neocortical
      activation results from muscarinic modulation of intrinsic neural oscillations
      and firing modes. Rhythmic-bursting pyramidal neurons in layer 5 may act as
      cortical pacemakers; if so, then modifying their discharge characteristics could
      alter local cortical networks. Larger, intercortical networks could also be
      modified, due to the widespread projections of NB neurons. Thus, NB cholinergic
      neurons may play a critical role in producing different states of neocortical
      function.

PMID- 1361199
TI  - Sixth International Conference on hand-arm vibration.

PMID- 1361198
TI  - Spontaneous synchronous synaptic calcium transients in cultured cortical neurons.
AB  - The firing pattern displayed by neuronal aggregates is thought to play a key role
      in cortical development and physiology. In this study, we have employed optical
      recording of intracellular calcium to monitor activity of multiple neurons
      simultaneously in primary cortical cultures. With this approach, we have observed
      spontaneous synchronous calcium transients among adjacent cortical neurons. These
      transients appear to be mediated by prominent spontaneous synaptic excitation, as
      they are enhanced by picrotoxin, a blocker of inhibitory GABAergic transmission,
      and reduced by antagonism of glutamate receptors or addition of TTX. After
      picrotoxin treatment, the calcium transients exhibit regular frequency and
      amplitude, and occur in synchrony with bursts of excitatory synaptic potentials
      every 10-20 sec. Using electrical stimulation, we have identified a relative
      refractory period, extending up to 5 sec after a synchronous burst, that may play
      a role in cell synchronization. NMDA receptor antagonists or reduced
      extracellular calcium levels lower the amplitude of the calcium transients yet
      fail to alter their frequency, suggesting that intracellular calcium levels may
      not be a major determinant of burst frequency. In contrast, mild depolarization
      with kainic acid (0.5-1 microM) increased burst frequency up to fivefold,
      suggesting a critical dependence of rhythmic activity on membrane potential.
      Chronic blockade of electrical activity with TTX beginning a few days after
      plating of cultures dampens the amplitude and significantly increases the
      frequency of calcium transients in mature cultures. These studies demonstrate
      that aggregates of cultured cortical neurons express synchronous firing activity
      in vitro and that this network activity is dependent in part on neuronal firing
      during development.

PMID- 1361200
TI  - Child and adolescent mental health: building a base for research and practice.
      The Third State of the Art and Science of Psychiatric Nursing Conference.

PMID- 1361201
TI  - Effect on cardiac sympathetic nerve activity of phenylephrine microinjected into
      the cat intermediolateral cell column.
AB  - 1. In anaesthetized cats the effect of the alpha 1-adrenoceptor agonist
      phenylephrine, microinjected into the left intermediolateral cell column of the
      spinal cord at the third thoracic level, was studied on left inferior cardiac
      nerve activity. 2. Microinjection of 100 nl of 10 or 40 mM-phenylephrine caused
      increases in inferior cardiac nerve activity in fifteen out of seventeen
      experiments. 3. The microinjection of the alpha 1-adrenoceptor antagonist
      alfuzosin (100 nl of 10 mM) into the intermediolateral cell column antagonized
      the excitatory response elicited by phenylephrine. 4. Increases in inferior
      cardiac nerve activity produced by glutamate and 5-hydroxytryptamine
      microinjected into the intermediolateral cell column were not antagonized by
      alfuzosin. 5. It is concluded that activation of alpha 1-adrenoceptors in the
      region of the intermediolateral cell column can cause an increase in the firing
      rate of sympathetic preganglionic neurones which innervate postganglionic
      neurones projecting into the inferior cardiac nerve.

PMID- 1361202
TI  - Induction of haemodynamic oscillations in the perfused rat liver by K+ channel
      blockers.
AB  - 1. Exposure of the isolated perfused (constant flow) rat liver to the K+ channel
      blockers 4-aminopyridine (4-AP) or Cs+ causes the appearance of oscillations in
      portal pressure and oxygen uptake. The oscillations have a mean frequency of
      0.035 Hz (2.1 cycles/min) and are fully reversible upon perfusion with blocker
      free saline. Tetraethylammonium (0.17-24.7 mM) does not induce oscillatory
      behaviour. 2. Reversible block of the 4-AP-induced oscillations is caused by 2 mM
      EGTA, or verapamil, chlorpheniramine, phentolamine or propranolol with IC50
      values of 0.42, 13.5, 15 or 11.5 microM respectively. The oscillations are
      transiently blocked by atropine (IC50 = 8.3 microM at peak inhibition) and are
      not affected by 2.7 microM-tetrodotoxin. 3. Endothelium-dependent vasorelaxants,
      Kupffer cell activity modifiers, retrograde perfusion, or removal of the portal
      vein from the circuit do not modify the oscillation parameters. 4. Oscillations
      are also caused by infusion of physiological concentrations of adrenaline or
      phenylephrine, but not isoprenaline. 5. The results provide new evidence for the
      existence of intrahepatic voltage-sensitive Ca2+, and 4-AP- and Cs(+)-sensitive
      K+ channels. We propose that the K+ channel blockers reveal an intrinsic
      oscillator in the liver, and that phasic vasoactivity may involve a minor
      contribution from neurotransmitter and/or hormonal substances.

PMID- 1361203
TI  - DNA analysis of HLA-DR, DQ, and DP alleles in children with polyarticular
      juvenile rheumatoid arthritis.
AB  - HLA-DR, DQ and DP alleles were determined by restriction fragment length
      polymorphism analysis and oligonucleotide probe hybridization of polymerase chain
      reaction amplified genomic DNA in 94 Caucasian children with polyarticular
      juvenile rheumatoid arthritis (JRA) [13 rheumatoid factor (RF)+ and 81 RF-] and
      100 healthy controls. HLA-DRw8, DQw4, DQA1*0401, DQB1*0402 were increased in
      frequency in those patients with RF seronegative disease, with highest
      frequencies seen in patients with young age at onset (< 5 years of age). These
      findings were similar to what we observed in children with pauciarticular JRA,
      especially those with young age at onset. DPB1*0301 was also found in increased
      frequency in the RF- group, and in particular those seronegative for antinuclear
      antibody. In contrast to what is observed in patients with pauciarticular JRA,
      the frequency of DPB1*0201 was not increased in any polyarticular JRA patient
      group. These data suggest that polyarticular JRA shares many genetic features
      with pauciarticular JRA.

PMID- 1361204
TI  - Retroperitoneal polyarteritis nodosa presenting as ureteral obstruction.
AB  - Polyarteritis nodosa (PAN) may be systemic or isolated in distribution and may
      involve virtually any organ or tissue in the body. Retroperitoneal PAN with
      ureteral obstruction as the first manifestation of the disease, to our knowledge,
      has not been previously reported. Two such unusual cases are described.

PMID- 1361205
TI  - Polyarteritis nodosa with aortic dissection: necrotizing vasculitis of the vasa
      vasorum.
AB  - A 59-year-old woman was admitted to our hospital with acute onset of chest pain.
      She had experienced high fever, weight loss, polyarthralgia, myalgia,
      polyneuropathy and hallucinations for 3 years before admission. The diagnosis of
      polyarteritis nodosa with hepatitis B surface antigenemia was made by muscle
      biopsy and serological examinations, and administration of prednisolone induced
      remission of all the manifestations. After developing the acute attack of severe
      chest pain, she died suddenly. At autopsy, a DeBakey type 1 aortic dissection was
      found and the immediate cause of death was found to be cardiac tamponade
      secondary to rupture of the aortic dissection. Microscopically, necrotizing
      inflammatory lesions were present in the medium sized vascular arteries
      throughout her body. Furthermore, necrotizing vasculitis was also found in the
      vasa vasorum of the adventitia and media of the thoracic aorta. The dissecting
      lesion was seen in the outer layer of the media. Our results suggest that
      spontaneous dissection of the aorta may be attributed to necrotizing vasculitis
      of the vasa vasorum.

PMID- 1361206
TI  - A metabolic assessment of the beta 1 selectivity of bisoprolol.
AB  - Twelve healthy volunteers were given single oral doses of bisoprolol 5 mg, 10 mg
      and 20 mg and atenolol 50 mg and 100 mg in a randomised, placebo-controlled
      study. The effects of these drugs on beta 2-stimulated hypokalaemia and
      hyperglycaemia (produced by intravenous terbutaline infusion) were studied.
      Comparable beta-blockade was achieved with bisoprolol 20 mg, and atenolol 50 mg
      and 100 mg as measured by attenuation of exercise heart rate. Measurements of
      areas under or over the curve (AUC and AOC) of hypokalaemic or hyperglycaemic
      response to terbutaline infusion showed that bisoprolol (10 mg and 20 mg) and
      atenolol (50 mg and 100 mg) were significantly less beta 1 selective than 5 mg
      bisoprolol. Furthermore, there was a trend towards decreasing beta 1 selectivity
      with increasing doses of bisoprolol. Bisoprolol, an effective once daily
      antihypertensive and antianginal treatment, has comparable beta 1 selectivity to
      atenolol as measured by metabolic response. At a dose of 5 mg, bisoprolol has a
      measurable impact on beta 1 receptors but minimal effect on beta 2 receptors.

PMID- 1361207
TI  - Early ambulation and discharge in 100 patients with burns of the foot treated by
      grafts.
AB  - Traditional treatment after grafting of foot, ankle, and lower leg burns is
      bedrest, limb elevation, and gradual ambulation only after 5 to 10 days. In 1982
      we suggested that aggressive surgical treatment and early ambulation could
      shorten hospital stay and decrease morbidity. Our treatment of these burns is
      excision and grafting, application of an Unna (dome paste) boot immediately in
      the operating room or the next morning, with normal ambulation 4 hours later and
      discharge of the patient if there are no other reasons for continued
      hospitalization. This paper reports the continuation of this plan in 100 patients
      treated since 1982 with a mean age of 28.8 +/- 16.9 (SD) years and burn size of
      3.7% +/- 4.4%. Sheet grafts were applied to 64% with a 96% take and narrowly
      meshed grafts to 36% with a 97% take. Results were excellent in 85 patients,
      satisfactory in ten, and poor in three who required another graft. Return to work
      was in 4.7 +/- 3 weeks. Unna boot application permits immediate ambulation,
      avoids frequent dressing changes, permits a brief or no hospital stay, and
      provides excellent graft take with prompt return to work.

PMID- 1361208
TI  - Endotoxin-induced uveitis in mice. 1. Induction of uveitis and role of T
      lymphocytes.
AB  - Endotoxin-induced uveitis (EIU) with a high frequency of posterior iris synechiae
      was induced by the systemic injection of 200 micrograms of endotoxin into C3H/HeN
      mice, an endotoxin-responsive strain. The cell number and the protein
      concentration within the aqueous humor began to increase 6 hours after the
      injection, achieving a peak at 24 hours, and decreased gradually thereafter.
      Inflammatory cells were observed in the anterior chamber, the vitreous body and
      near the iris-ciliary body histologically. Most of the inflammatory cells were
      polymorphonuclear cells. On the other hand, C3H/HeJ mice, an endotoxin
      unresponsive strain, showed no increase in either cell number or protein
      concentration in the aqueous humor after endotoxin administration. Pretreatment
      of C3H/HeN mice with anti-Thy-1.2 antibody significantly decreased both the cell
      number and the protein concentration in the aqueous humor and the incidence of
      the posterior synechiae, as compared with the control group. Anti-CD4 antibody
      also significantly reduced the severity of EIU, while anti-CD8 antibody had no
      influence on the disease. Anti-IFN-gamma antibody increased the cell number in
      the aqueous humor. These observations indicate that T lymphocytes, especially
      CD4+ T lymphocytes, have an extremely important role in the development of EIU in
      mice.

PMID- 1361209
TI  - [Beta blockers with vasodilating properties in hypertension].

PMID- 1361211
TI  - Nutrition and Metabolism in Renal Disease. Proceedings of the 6th International
      Conference in Renal Nutrition and Metabolism. Harrogate, United Kingdom, August
      26-30, 1991.

PMID- 1361210
TI  - The MTT cell viability assay for cytotoxicity testing in multidrug-resistant
      human leukemic cells.
AB  - The MTT cell viability assay is widely used in determining drug sensitivity
      profiles for patients with hematological malignancies and in primary screening of
      potential chemotherapeutic drugs. Because the multidrug resistance (MDR)
      phenotype is associated with these malignancies, and since many vital dyes are
      effluxed from MDR expressing cells, we have investigated whether the MDR
      phenotype interferes with the MTT assay. In CCRF-CEM and K562 human leukemic cell
      lines and drug-resistant sub-lines developed from them, comparison of the MTT
      assay with other cell viability assays showed significant variation in IC50
      concentrations, although the resistance relative to the sensitive parent cell was
      correlated. Inclusion of verapamil, an inhibitor of drug efflux activity, had no
      effect on the MTT assay.

PMID- 1361213
TI  - Homology of a 150K cytoplasmic dynein-associated polypeptide with the Drosophila
      gene Glued.

PMID- 1361212
TI  - The Ncypt1 gene from Neurospora crassa is located on chromosome 2: molecular
      cloning and structural analysis.
AB  - Small GTP-binding proteins are encoded by ras-like genes and play a central role
      in cell differentiation and membrane vesicle transport. By screening genomic and
      cDNA libraries of the Ascomycete fungus Neurospora crassa with Zmypt genes from
      Zea mays we have isolated a member of the ypt gene family, Ncypt1. The gene
      resides on a 4 kb fragment of genomic DNA and contains four introns, which
      interrupt the coding sequence of a protein of 203 amino acid residues. The Ncytp1
      gene was assigned to a single-copy gene encoding a transcript of 1.5 kb and a
      protein of 26,000 daltons. The gene maps on linkage group IIR between DB0001 and
      ccg-2 close to the Fsr-3 locus. Analysis of the nucleotide sequence and the
      deduced protein sequence revealed a striking homology to yeast, mouse and human
      genes encoding small GTP-binding proteins that are related to the ras supergene
      family. Homology was most significant to ypt1 from Schizosaccharomyces pombe, Mus
      musculus and Homo sapiens sharing 84.8%, 82.3%, and 82.3% identity, respectively.
      Common domains present in other small GTP-binding proteins were identified in the
      predicted sequence of the NCYPT1 protein, and the arrangement of peptide motifs
      sharing similarity with well characterized, small GTP-binding proteins suggests
      that the NCYPT1 protein is a GTPase. The C-terminal region extending from amino
      acid residues 175 to 199 shares only weak amino acid sequence similarity with
      other eukaryotic GTPases. Like other RAS proteins the NCYPT1 protein contains two
      conserved C-terminal cysteine residues, suggesting post-translational
      modification(s) by fatty acylation required for membrane anchoring. The high
      degree of homology between the NCYPT1 protein and eukaryotic YPT proteins
      suggests that NCYPT1 could be involved in the control of secretory processes.

PMID- 1361215
TI  - A highly potent and selective N-methyl-D-aspartate receptor antagonist from the
      venom of the Agelenopsis aperta spider.
AB  - Agatoxin-489, extracted from the venom of the Agelenopsis aperta spider, was
      studied on acutely isolated perfused hippocampal neurons of rat using the
      concentration clamp technique. Agatoxin-489 proved to be a selective N-methyl-D
      aspartate antagonist; responses to applications of N-methyl-D-aspartate or L
      aspartate were blocked by concentrations of agatoxin-489 ranging between 0.1 nM
      and 1 microM, while responses to kainate were not affected by agatoxin-489 at
      concentrations up to 10 microM. The actions of agatoxin-489 against responses to
      N-methyl-D-aspartate or L-aspartate were use- and voltage-dependent, being less
      pronounced with an increase in the holding potential from -100 to -30 mV. The
      action of agatoxin-489 could be completely or partially reversed only after
      washout in the presence of an N-methyl-D-aspartate agonist. The washout was more
      effective at positive membrane potentials ranging from 0 to +20 mV. These results
      imply that the spider toxin agatoxin-489, like dizocilpine, is a potent and
      selective N-methyl-D-aspartate antagonist which preferentially interacts with
      activated N-methyl-D-aspartate receptors and/or open N-methyl-D-aspartate
      activated ionic channels.

PMID- 1361214
TI  - Retinoic acid alters hindbrain Hox code and induces transformation of rhombomeres
      2/3 into a 4/5 identity.
AB  - It has been suggested that Hox genes play an important part in the patterning of
      limbs, vertebrae and craniofacial structures by providing an ordered molecular
      system of positional values, termed the Hox code. Little is known about the
      nature of the signals that govern the establishment and regulation of Hox genes,
      but retinoic acid can affect the expression of these genes in cell lines and in
      embryonic tissues. On the basis of experimental and clinical evidence, the
      hindbrain and branchial region of the head are particularly sensitive to the
      effects of retinoic acid but the phenotypes are complex and hard to interpret,
      and how and if they relate to Hox expression has not been clear. Here we follow
      the changes induced by retinoic acid to hindbrain segmentation and the branchial
      arches using transgenic mice which contain lacZ reporter genes that reveal the
      endogenous segment-restricted expression of the Hox-B1 (Hox-2.9), Hox-B2(Hox-2.8)
      and Krox-20 genes. Our results show that these genes rapidly respond to exposure
      to retinoic acid at preheadfold stages and undergo a progressive series of
      changes in segmental expression that are associated with specific phenotypes in
      hindbrain of first branchial arch. Together the molecular and anatomical
      alterations indicate that retinoic acid has induced changes in the hindbrain Hox
      code which result in the homeotic transformation of rhombomeres (r) 2/3 to an
      r4/5 identity. A main feature of this rhombomeric phenotype is that the
      trigeminal motor nerve is transformed to a facial identity. Furthermore, in
      support of this change in rhombomeric identity, neural crest cells derived from
      r2/3 also express posterior Hox markers suggesting that the retinoic acid-induced
      transformation extends to multiple components of the first branchial arch.

PMID- 1361216
TI  - Is the neuronal ATP release from guinea-pig vas deferens subject to alpha 2
      adrenoceptor-mediated modulation?
AB  - The effects of a variety of alpha 2-adrenoceptor agonists and antagonists were
      studied on stimulation-evoked release of endogenous ATP, measured by the
      luciferin-luciferase assay, and on the release of [3H]noradrenaline from the
      guinea-pig vas deferens. The biphasic mechanical contraction of the guinea-pig
      smooth muscle was recorded concomitantly. The alpha 2-adrenoceptor agonist,
      xylazine (1 microM) inhibited the field stimulation-evoked (8 Hz, 0.1 ms, 480
      shocks) release of ATP and [3H]noradrenaline, and both phases of the contraction.
      The inhibitory effect of xylazine on the release of ATP, noradrenaline and muscle
      contraction was prevented by the selective alpha 2-adrenoceptor antagonist, CH
      38083 [7,8-(methylenedioxi)-14 alpha-alloberbanol, 1 microM]. In the presence of
      prazosin (0.1-1 microM) or WB 4101 [2-(2,6-dimethoxyphenoxyethyl)aminomethyl- 1,4
      benzodioxane hydrochloride, 0.1-1 microM], i.e. under the condition when the
      effect of noradrenaline on postjunctional alpha 1-adrenoceptors was excluded, the
      stimulation-evoked release of [3H]noradrenaline was significantly enhanced,
      however, the release of endogenous ATP and also both phases of contraction were
      reduced. In the presence of prazosin, xylazine was able to inhibit the
      stimulation-evoked release of ATP. In vas deferens dissected from reserpine
      pretreated (2 x 5 mg/kg, i.p.) guinea-pigs, the content of noradrenaline was 0.5%
      of control and there was no detectable evoked release of noradrenaline. Under
      this condition, the release of ATP evoked by electrical stimulation was still
      detectable, but the amount of ATP was much smaller than that measured from
      control animals. Xylazine did not reduce the release of ATP. Oxymetazoline, a
      relatively selective alpha 2-adrenoceptor agonist failed to inhibit the release
      of [3H]noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361217
TI  - Synaptic activation of rat adrenal medulla examined with a large photodiode array
      in combination with a voltage-sensitive dye.
AB  - The adrenal medulla is innervated by sympathetic preganglionic nerve fibers in
      the splanchnic nerve. Synaptic activation of the adrenal medulla causes
      catecholamine secretion which is known to be modified by various neuropeptides
      and other factors. To understand the neuronal control mechanism of catecholamine
      secretion, it is necessary to know the transfer function at the synapse and how
      it is affected by such factors. By using a large photodiode array in combination
      with a voltage-sensitive dye, membrane potential changes in a slice of the rat
      adrenal gland were recorded upon brief local electrical stimulation. Electrical
      signals were recorded only on the portion of the diode array corresponding to the
      medulla. In a typical record, a spike and an underlying slow potential were
      observed following a small deflection due to a presynaptic nerve action
      potential. Both the spike and slow potential were blocked in Ca(2+)-free solution
      or by hexamethonium, a nicotinic antagonist, but were not affected by atropine, a
      muscarinic antagonist. The slow potential was interpreted as a nicotinic synaptic
      potential in the chromaffin cells and the spike as a population action potential.
      A double pulse experiment revealed that the chromaffin cell action potential
      began to fail only when the stimulus interval was less than 50 ms (20 Hz). When
      the stimulus intensity was reduced, the minimal response was found to behave in
      an all-or-none fashion. This suggested that one nerve fiber is innervating a
      cluster of chromaffin cells, which may correspond to a previously histologically
      identified "complex" of cells [Hillarp (1946) Acta. anat. 4, Suppl. 1]. Each
      complex was innervated by approximately four nerve fibers.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1361218
TI  - Somatostatin release is enhanced in the hippocampus of partially and fully
      kindled rats.
AB  - The release of somatostatin (somatostatin-like immunoreactivity) from hippocampal
      slices during the development of hippocampal kindling in rats was measured under
      resting and depolarizing conditions. Preliminary experiments in naive rats showed
      that the spontaneous efflux of somatostatin (4.0 +/- 0.3 fmol/ml every 10 min)
      was independent of external Ca2+ but was reduced to 71.5 +/- 6% of baseline (P <
      0.05) during 20 min incubation with 5 microM tetrodotoxin. Neuronal
      depolarization with 25, 50 and 100 mM KCl induced a Ca(2+)-dependent somatostatin
      release, respectively 4.3 +/- 0.4, 16.7 +/- 1.6 and 22.0 +/- 1.3 times baseline
      (P < 0.01). Veratridine caused a dose-dependent Ca2+ and tetrodotoxin (5 microM)
      sensitive release ranging from 6.5 +/- 0.1 to 13.0 +/- 1.4 times baseline at 1.4
      microM and 50 microM respectively (P < 0.01). One week after the last of three
      consecutive stage 5 seizures (full seizure expression) or 48 h after the last
      stage 2 stimulation (preconvulsive stage), 50 mM KCl-induced somatostatin release
      was significantly higher (1.8 +/- 0.1, P < 0.01) than in shams (animals implanted
      with electrodes but not stimulated) in the stimulated and contralateral
      hippocampus. Somatostatin release measured under resting conditions was increased
      by 1.5 times in the stimulated hippocampus at stage 2 (P < 0.05) and by 2.2 and
      1.7 times in both hippocampi at stage 5 (P < 0.01). Forty-eight hours after the
      induction of a single afterdischarge no significant changes were found in either
      spontaneous or 50 mM KCl-induced release of somatostatin.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1361221
TI  - Neurotransmitter modulation of calcium channels is dependent on the charge
      carrier used in the recording of currents.
AB  - Currents through calcium channels were recorded using calcium, barium and
      strontium as charge carriers in NG108-15 cells. The mean normalised peak current
      amplitude at 0 mV was not significantly different between the charge carriers;
      however, the sustained component (measured at the end of the 500 ms command step)
      was ca. 3 times larger in barium and strontium. Further, the inhibition by
      acetylcholine or noradrenaline, although the same at the peak of the current
      envelope, was significantly greater on the sustained portion of the current for
      barium and strontium. Increasing internal calcium-buffering (to reduce calcium
      dependent inactivation with calcium as the charge carrier) did not increase the
      amount of inhibition of the sustained portion of current. These results suggest a
      cautious approach to analysis of neurotransmitter modulation of calcium currents
      using other charge carriers than calcium.

PMID- 1361219
TI  - Control of 40-Hz firing of reticular thalamic cells by neurotransmitters.
AB  - This study bears on the control exerted by neurotransmitters on the expression of
      a 40-Hz pacemaker activity observed in reticular thalamic cells. Experiments were
      conducted in urethane-anaesthetized rats using extracellular recordings and local
      applications of antagonists against the neurotransmitters involved in the
      modulation of reticular thalamic cells. All drugs were dissolved in a Ringer's
      solution (pH 7.4) and were applied in small quantities (25-150 nl) by pressure
      through one barrel of a micropipette assembly. Forty-Hertz firing was abolished
      by local application of the alpha 1 antagonist prazosin and by bilateral lesion
      of the locus coeruleus. Local applications of glutamate antagonists reduced the
      rate of discharges by 30-50% as did cortical cooling or complete transection of
      the internal capsule. Conversely, scopolamine exerted a permissive action on the
      expression of 40-Hz activities; many spontaneously bursting units started firing
      at 40 Hz under the influence of this muscarinic antagonist. Since reticular
      thalamic cells are GABAergic and synaptically coupled via axonal collaterals, we
      investigated how GABAergic drugs affected the regular firing of these cells.
      Local applications of bicuculline produced a transient increase of the firing
      rates while the application of GABA induced intermittent pauses on a background
      of regular discharges. The application of piperidine-4-sulphonic acid, a GABAA
      receptor agonist, produced a similar effect. The length of pauses generated by
      piperidine was statistically analysed. It was found that the duration of short
      pauses was a multiple integer of the mean interspike interval of surrounding
      discharges. The preservation of the period and phase of the rhythm across the
      pauses implies that a subthreshold oscillation was presented into the cells
      during the arrests of discharges. Given the mode of action of noradrenaline and
      acetylcholine on reticular thalamic neurons, and considering a possible
      metabotropic action of glutamate, the above results suggest that deactivation of
      a leaky K conductance is critically involved in the regular firing of these cells
      in urethane-anaesthetized rats. Alternatively, because reticular cells are
      coupled via inhibitory synapses, it is proposed that the 40-Hz firing frequency
      reflects, in the frequency domain, a point of equilibrium in the reticular
      thalamic network when the leaky K conductance is fully deactivated by the
      metabotropic effects of monoamines and/or excitatory amino acids.

PMID- 1361220
TI  - An experimental arthritis in rats: dorsal horn aspartate and glutamate increases.
AB  - Amino acid release in the dorsal horn of awake rats was examined by microdialysis
      during the development of arthritis induced by injection of 3% kaolin and 3%
      carrageenan into the knee joint. The following amino acids were measured by HPLC
      at baseline and for the first 8 h of arthritis: Asp, Glu, Asn, Gln, Ser, Gly and
      Tau. An initial increase in all amino acids examined was observed on injection of
      the knee joint with kaolin and carrageenan. Subsequently, there was a peak
      increase in Asp (184%), Glu (188%) and Gln (146%) during a prolonged release
      phase which began at 3.5 h and persisted at least 8 h. While Asn showed no
      changes from baseline, extracellular fluid concentrations of Ser, Gly and Tau
      were variable. This data indicates that the induction of arthritis is accompanied
      by an increased release of excitatory amino acids Asp and Glu which may be
      important in the generation of acute arthritis.

PMID- 1361222
TI  - Is forskolin stimulation of rat striatal tyrosine hydroxylase dependent on
      adenylate cyclase activation?
AB  - Because some responses to forskolin are adenosine 3',5'-cyclic phosphate (cyclic
      AMP) independent, we investigated the involvement of adenylate cyclase in the
      stimulatory effect of forskolin on synaptosomal tyrosine hydroxylase (TH)
      activity of rat striatum. The forskolin analogue, 1,9-dideoxyforskolin, which
      mimics the cyclic AMP-independent effects of forskolin, was a very weak activator
      of both striatal adenylate cyclase and tyrosine hydroxylase activities, whereas
      forskolin stimulated the two enzymes effectively and with similar potencies.
      Moreover, exposure of synaptosomes to the specific cyclic AMP antagonist Rp
      adenosine 3',5'-cyclic phosphorothioate reduced basal TH activity and
      counteracted the stimulatory effect on the enzyme activity by submaximal
      concentrations of forskolin. These results provide circumstantial evidence that
      in striatal dopaminergic nerve terminals a presynaptic adenylate cyclase mediates
      the stimulation of TH activity by forskolin.

PMID- 1361223
TI  - Increased plasma concentrations of aspartate, glutamate and glycine in
      Parkinson's disease.
AB  - We measured fasting plasma amino acids in 20 patients with Parkinson's disease
      (PD) and 20 controls matched for age and sex. PD patients had significant
      elevations in plasma levels of aspartate, glutamate and glycine. The levels of
      other amino acids were not significantly different from those found in controls.
      No correlation was noted between PD severity and the degree of abnormality of
      plasma amino acids. We conclude that excitatory amino acids may be altered in
      patients with PD, and raise the possibility that neuroexcitotoxic mechanisms may
      be involved in the neurodegeneration of PD.

PMID- 1361225
TI  - Neuroprotective synergism of 2-amino-3-phosphonoproprionate (D,L-AP3) and MK-801
      against ibotenate induced brain injury.
AB  - The neuroprotective characteristics of the functional antagonist of metabotropic
      stimulated phosphoinositide hydrolysis, 2-amino-3-phosphonoproprionate (D,L-AP3),
      were examined alone and in combination with the non-competitive N-methyl-D
      aspartate (NMDA) antagonist, MK-801, against ibotenate induced brain injury.
      Postnatal day (PND) 7 rats received unilateral stereotaxic intrastriatal
      injections of 10 nmol ibotenate and treated with either D,L-AP3 (600 nmol i.c.),
      MK-801 (1 mg/kg i.p.) or both. The severity of brain injury was assessed on PND
      12 by comparison of the weights of injected and contralateral cerebral
      hemispheres. Ibotenate induced injury was partially reduced by treatment with MK
      801 (34.0 +/- 4.4% protection, P < 0.05 vs. PBS treated, independent t-test) but
      not D,L-AP3. However, combined treatment with both MK-801 and D,L-AP3 produced
      marked synergistic neuroprotection (83.5 +/- 7.6% protection, P < 0.001 vs. PBS
      treated, independent t-test). The data suggest that metabotropic stimulated
      phosphoinositide hydrolysis contributes to excitotoxic neuronal injury in the
      presence of concurrent ionotropic receptor activation.

PMID- 1361224
TI  - Endogenous extracellular glutamate accumulation in rat neocortical cultures by
      reversal of the transmembrane sodium gradient.
AB  - Glutamate excites receptors located on neurons that cause calcium and sodium
      influx involved in excitatory synaptic transmission. During ischemia, excess
      glutamate is present in the extracellular space of brain tissue, leading to
      abnormal levels of calcium influx and eventually to cell death. In mixed
      neuronal/glial cell cultures we have found that reduction of extracellular sodium
      concentration below approximately 10 mM causes marked increases in glutamate and
      aspartate in medium collected 10 min after changing to low sodium. Various data
      indicate that the accumulated glutamate comes from reversal of normal cellular
      glutamate uptake, a process also thought to occur during ischemia.

PMID- 1361226
TI  - Effect of carbachol on luminal release of somatostatin from isolated perfused rat
      duodenum.
AB  - The dynamic release of somatostatin-like immunoreactivity (SLI) from duodenum
      into the lumen was studied in the isolated, vascularly perfused rat duodenum. The
      luminal release of duodenal SLI was stimulated by a cholinergic agonist,
      carbachol, and the carbachol-induced release of SLI was completely blocked by
      atropine, but not by hexamethonium. These data suggest that the luminal release
      of SLI from rat duodenum is under the control of a cholinergic muscarinic
      stimulation. The ratio of somatostatin-14 to somatostatin-28 in picograms was
      about 1 during basal release but increased to approximately 2 during carbachol
      stimulation.

PMID- 1361227
TI  - Symposium on Enzyme Inhibition and Drug Discovery. Antwerp, Belgium, 6 November
      1992. Abstracts.

PMID- 1361228
TI  - [Pharmacology aspects of glaucoma].
AB  - The aim of all treatment for glaucoma is to lower intra-ocular pressure. During
      the past decade, the short-action cholinergic agonists, eserine and pilocarpine,
      that have been used for over a hundred years have been replaced as the drugs of
      choice by beta-blockers, in particular the non-selective beta-blocker, timolol
      maleate. Of the series of drugs developed in recent years for the treatment of
      glaucoma, two types--carbonic anhydrase inhibitors and prostaglandin analogues-
      are undergoing phase III trials. The article provides an account of the
      pharmacological basis of glaucoma treatment today and in the immediate future.

PMID- 1361229
TI  - [Use of inhaled beclomethasone dipropionate in adult asthma].
AB  - Beclomethasone dipropionate has now been used for more than 10 years during which
      our knowledge of how to use inhaled corticosteroids has gradually improved: high
      dose initial treatment followed by progressive reduction down to the minimum
      effective dosage; administration in 2 daily doses when the asthma is stable and 4
      daily doses in case of instability; mild and transient undesirable effects, often
      minimized by a correct use of the inhaler; effectiveness assessed from bronchial
      hyper-reactivity and respiratory function tests, reduction or avoidance of oral
      corticosteroid therapy, or results of association with other treatments, and in
      particular bronchodilators. When exactly should inhaled corticosteroid therapy
      should be started and how long should it be pursued are controversial points, but
      an early and prolonged treatment must probably be recommended.

PMID- 1361230
TI  - The importance of being flexible.

PMID- 1361231
TI  - Molecular mimicry of hepatitis B surface antigen by an anti-idiotype-derived
      synthetic peptide.
AB  - Monoclonal antibody 2F10 is an "internal-image" anti-idiotype (anti-id) antibody
      capable of mimicking the group-specific "a" determinant of human hepatitis B
      surface antigen (HBsAg). By mRNA sequencing and computer-assisted molecular
      modeling of monoclonal antibody 2F10, we identified a 15-amino acid region of the
      heavy-chain hypervariable region that has partial residue homology with sequences
      of the "a" determinant epitopes of HBsAg. We have established that a linear 15
      mer peptide from a contiguous region on the anti-id antibody can (i) generate
      anti-HBsAg-specific antibodies when injected into mice, (ii) prime murine lymph
      node cells for in vitro HBsAg-specific T-cell proliferative responses, and (iii)
      stimulate in vitro human CD4+ T cells that were primed in vivo to HBsAg by
      natural infection with hepatitis B virus or vaccination with a commercially
      available HBsAg vaccine. Significantly, this peptide could also stimulate CD4+ T
      cells of human hepatitis B virus carriers. We conclude that a 15-mer peptide
      derived from the anti-id sequence can duplicate the B- and T-cell stimulatory
      activity of the intact anti-id antibody and the antigen that is mimicked, HBsAg.

PMID- 1361232
TI  - Detection of glutamine synthetase in the cerebrospinal fluid of Alzheimer
      diseased patients: a potential diagnostic biochemical marker.
AB  - In this report, 8- and 2-azidoadenosine 5'-[gamma-32P]triphosphate were used to
      examine cerebrospinal fluid (CSF) samples for the presence of an ATP binding
      protein unique to individuals with Alzheimer disease (AD). A 42-kDa ATP binding
      protein was found in the CSF of AD patients that is not observed in CSF from
      normal patients or other neurological controls. The photolabeling is saturated
      with 30 microM 2-azidoadenosine 5'-[gamma-32P]triphosphate. Photoinsertion can be
      totally prevented by the addition of 25 microM ATP. Photoinsertion of 2
      azidoadenosine 5'-triphosphate into the protein is only weakly protected by other
      nucleotides such as ADP and GTP, indicating that this is a specific ATP binding
      protein. A total of 83 CSF samples were examined in a blind manner. The 42-kDa
      protein was detected in 38 of 39 AD CSF samples and in only 1 of 44 control
      samples. This protein was identified as glutamine synthetase [GS; glutamate
      ammonia ligase; L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] based on
      similar nucleotide binding properties, comigration on two-dimensional gels,
      reaction with a polyclonal anti-GS antibody, and the presence of significant GS
      enzyme activity in AD CSF. In brain, GS plays a key role in elimination of free
      ammonia and also converts the neurotransmitter and excitotoxic amino acid
      glutamate to glutamine, which is not neurotoxic. The involvement of GS, if any,
      in the onset of AD is unknown. However, the presence of GS in the CSF of terminal
      AD patients suggests that this enzyme may be a useful diagnostic marker and that
      further study is warranted to determine any possible role for glutamate
      metabolism in the pathology of AD.

PMID- 1361233
TI  - Recycling and phosphorylation of eukaryotic initiation factor 2 on 60S subunits
      of 80S initiation complexes and polysomes.
AB  - Phosphorylation of the alpha-subunit (38 kDa) of eukaryotic initiation factor 2
      (eIF-2 alpha) regulates initiation of protein synthesis in eukaryotic cells. This
      phosphorylation is enhanced in cycloheximide-treated heme-deficient reticulocyte
      lysates in which polysomes are maintained. In early heme deficiency prior to
      polysome disaggregation, eIF-2(alpha P) accumulates primarily on the 60S subunits
      of polysomes. Further, isolated polysomes contain eIF-2 alpha that is efficiently
      phosphorylated in vitro by heme-regulated inhibitor (HRI). Immunoblot analysis of
      eIF-2 distribution in sucrose gradients of actively protein-synthesizing lysates
      indicates that eIF-2 is distributed at low levels throughout the polysome
      profiles. These findings suggest that polysome-bound eIF-2 alpha is a target of
      HRI under physiological conditions. The presence of eIF-2 on the 60S subunits of
      polysomes is incompatible with the conventional model in which eIF-2 is recycled
      during the joining of the 48S preinitiation complex and the 60S subunit to form
      the 80S initiation complex. A modified model is presented with emphasis on the
      translocation of eIF-2 from the 40S ribosomal subunit of the 48S preinitiation
      complex (eIF-2.GTP.Met-tRNA(f).40S.mRNA) to the 60S subunit of the 80S initiation
      complex.

PMID- 1361234
TI  - Activity of the Hsp70 chaperone complex--DnaK, DnaJ, and GrpE--in initiating
      phage lambda DNA replication by sequestering and releasing lambda P protein.
AB  - Initiation of DNA replication by phage lambda requires the ordered assembly and
      disassembly of a specialized nucleoprotein structure at the origin of
      replication. In the disassembly pathway, a set of Escherichia coli heat shock
      proteins termed the Hsp70 complex--DnaK, DnaJ, and GrpE--act with ATP to release
      lambda P protein from the nucleo-protein complex, freeing the DnaB helicase for
      its DNA-unwinding reaction. To investigate the mechanism of the release reaction,
      we have examined the interaction between P and the three heat shock proteins by
      glycerol gradient sedimentation and gel electrophoresis. We have discovered an
      ATP-dependent ternary interaction between P, DnaK, and DnaJ; this P.DnaK.DnaJ
      complex is dissociated by GrpE. We have concluded that the function of the Hsp70
      complex in sequestering and releasing P protein provides for the critical step in
      the disassembly pathway. Based on our data and other work on protein folding, the
      formation of the P.DnaK.DnaJ complex might involve a conformational shift to a
      folding intermediate of P.

PMID- 1361235
TI  - Effects of the phthalazinone azelastine on epidermal metabolism after mechanical
      skin irritation.
AB  - In female NMRI mice, the phthalazinone azelastine was administered orally once
      daily over 7 days. The drug influenced the epidermal thymidine triphosphate and
      amino acid incorporation rates at doses between 1 and 5 mg/kg. In control mice,
      an epidermal hyperproliferation induced by abrasion of superficial epidermal
      layers was characterized by enhanced prostaglandin and leukotriene concentrations
      in epidermal homogenate, an increase in thymidine triphosphate and amino acid
      incorporation and an increase in epidermal thickness. In mice treated with 1
      mg/kg azelastine HCl, this epidermal reaction was changed. Compared to controls,
      the increase in leukotriene concentration was diminished, and that of
      prostaglandins was enhanced. The incorporation of thymidine triphosphate and of
      amino acids as well as the epidermal thickness and the ratio cell count/epidermal
      thickness were increased in irritated skin of azelastine-treated mice. In
      conclusion, azelastine influences the epidermal metabolism in irritated and
      unirritated skin. Therefore, a beneficial role of this phthalazinone in the
      treatment of psoriasis and related skin disorders seems to be possible.

PMID- 1361236
TI  - The role of imidazoline receptors in blood pressure regulation.
AB  - Using the ligands [3H] clonidine and [3H] idazoxan, nonadrenergic imidazoline
      preferring binding sites have been identified in a range of tissues from several
      species including man. These sites may represent a new family of receptors. An
      endogenous ligand and potential clonidine displacing substance has been
      identified. There is strong evidence for an involvement of the nonadrenergic
      imidazoline [3H] clonidine labelled sites in the nucleus reticularis lateralis in
      blood pressure regulation, and some evidence for a role in sodium regulation in
      the kidney for the [3H] idazoxan labelled sites. Some drugs which were previously
      thought to act via alpha 2-adrenoceptors, may mediate their effects in part via
      these imidazoline sites.

PMID- 1361238
TI  - [Beta agonists in asthma patients. Useful or hazardous?].

PMID- 1361239
TI  - Transactions of the XXIII Nordic Congress in Clinical Chemistry. Reykjavik,
      Iceland, 11-14 August 1992. Abstracts.

PMID- 1361237
TI  - Characterisation of monoclonal antibodies against a fimbrial structure of
      Salmonella enteritidis and certain other serogroup D salmonellae and their
      application as serotyping reagents.
AB  - A panel of 13 monoclonal antibodies from different hybridomas was produced
      against a novel salmonella fimbrial antigen expressed predominantly by Salmonella
      enteritidis strains. The specificity of the monoclonal antibodies to this antigen
      (SEF14) was confirmed by enzyme-linked immunosorbent assay (ELISA) using purified
      SEF14, immune electron microscopy and, with 11 monoclonal antibodies, the
      identification of a repeating protein subunit (14,300kDa) on the antigen.
      Blocking-ELISA with the monoclonal antibodies identified epitopes in at least
      three, non-overlapping clusters which appeared evenly distributed on SEF14 in
      immune electron microscopy. The use of the monoclonal antibodies in direct
      binding ELISA on a range of salmonella serotypes suggested that the epitopes on
      SEF14 are highly conserved and were expressed by all the S enteritidis strains
      examined; some strains of S dublin and the only strain of S moscow available were
      the only other serotypes that expressed SEF14. A latex agglutination reagent
      based on a monoclonal antibody was developed and used to test for SEF14 on 280
      strains (representing 120 serotypes in 24 serogroups of salmonellae) that had
      been grown on Sensitest agar for 18 hours at 37 degrees C. All S enteritidis
      strains (64) and most S dublin strains (28 of 33) produced SEF14 as did the two
      strains representing S blegdam and S moscow. SEF14 was not detected in any other
      strains of serotypes from serogroup D or from any other serogroup examined.

PMID- 1361240
TI  - Trend towards decreased survival in patients infected with HIV resistant to
      zidovudine.
AB  - The survival of 35 patients with AIDS or advanced HIV infection on treatment with
      zidovudine was related to the viral sensitivity to the drug and to the CD4+ cell
      count. 14 patients died, the survivors were followed up for an average of 804
      days. In a univariate Cox model, survival was strongly related to log IC90 (p =
      0.0003) and to the CD4+ count (p = 0.0002). In a bivariate model, log IC90 and
      the CD4+ count contributed to the prediction of survival (p = 0.12 and 0.06,
      respectively). Large studies of combination or alternation therapy with several
      anti-HIV drugs should be given high priority.

PMID- 1361241
TI  - Absence of an association between enteric parasites in the manifestations and
      pathogenesis of HIV enteropathy in gay men. The GI/HIV Study Group.
AB  - 49 gay men confirmed to be infected with the human immunodeficiency virus (HIV)
      and 9 HIV seronegative gay men participated in a pilot study comparing clinical
      status and enteric parasite load with gastrointestinal structure, function and
      symptomatology. Cases included 16/49 (33%) men who were CDC stage II, 7/49 (14%)
      who were CDC stage III, and 26/49 (53%) who were CDC stage IV. The mean CD4
      lymphocyte count was 476 +/- 199 (SD)/microliter. The prevalence of enteric
      parasitic flora was similar in HIV seropositive patients and controls. Seven
      cases had enteric infection with pathogenic agents including 3 patients with
      Entamoeba histolytica, and 4 patients with Giardia lamblia, one of whom also had
      cryptosporidiosis. Other cases were most frequently colonized with Blastocystis
      hominis (44%) and Endolimax nana (41%) regardless of the HIV clinical status. HIV
      seropositive patients with enteric parasitic colonization tended to have lower
      mean levels of serum IgA than cases without parasites. Duodenal morphometric
      mucosal changes demonstrated a significant decrease in the mean villous height (p
      < 0.01) with no elongation of the crypt depth in HIV-infected patients with and
      without diarrhea compared to controls. Despite gastrointestinal symptoms
      including diarrhea and weight loss being more prevalent in HIV infected
      individuals than controls, no correlations were found between the presence of
      particular enteric parasites, gastrointestinal symptomatology, the clinical HIV
      status of the CD4-lymphocyte count, the malabsorption of D-xylose or morphometric
      changes in the duodenum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361242
TI  - [Developments in the treatment of myocardial infarction in Switzerland 1986-1990:
      results of a population survey].
AB  - The Swiss cantons of Vaud and Fribourg participate in the international MONICA
      project (MONI-toring of trends and determinants in CArdiovascular disease).
      Within this context, drug therapies and procedures were recorded during two
      separate years (1986 and 1990) for all hospitalizations of men aged 25 to 64 with
      the diagnosis of myocardial infarction. The medical files were reviewed to
      classify this diagnosis as possible or definite on the basis of the symptoms, the
      ECG results and the enzymatic tests. The two study populations (n = 318 in 1986
      and n = 332 in 1990) are comparable with respect to age, history of ischemic
      heart disease and initial care. In 1990, half of the patients arrived at hospital
      in less than 3 hours, the median time delay being 4 hours for those first
      attending a general practitioner and 2 hours for those transferred directly. The
      frequency of treatments between 1986 and 1990 is compared only for cases with a
      definite diagnosis of myocardial infarction (respectively n = 217 and n = 223).
      The proportion of patients given thrombolytic therapy rose from 9% to 44% (p <
      0.005) and from 51% to 95% (p < 0.005) for those treated with antiplatelet drugs,
      whereas the proportion fell from 72% to 55% (p < 0.005) for calcium blockers and
      from 33% to 24% (p < 0.05) for inotropic drugs. The use of anticoagulants (in 98%
      of patients) and of beta blockers (in 57%) remained stable across time.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1361243
TI  - An obese 14-year-old girl with persistently elevated liver-associated enzymes.

PMID- 1361244
TI  - [Family Health Conference. Covilha, 20-22 February 1992].

PMID- 1361245
TI  - Technique of cholangiography and cystic-duct choledochoscopy at the time of
      laparoscopic cholecystectomy for laser lithotripsy.

PMID- 1361246
TI  - Non 5-HT1A/5-HT1C [3H]5-HT binding sites in the hamster, opossum, and rabbit
      brain show similar regional distribution but different sensitivity to beta
      adrenoceptor antagonists.
AB  - We have used receptor autoradiography to investigate the distribution and
      pharmacological profile of non 5-HT1A/5-HT1C[3H]5-hydroxytryptamine binding sites
      in the brain of rabbits, hamsters and opossums. These data were compared to those
      found under similar conditions in the brain of rats and guinea pigs, species
      which are known to possess 5-HT1B and 5-HT1D receptors, respectively. In the
      presence of 100 nM 8-OH-DPAT and mesulergine, the regional distribution of [3H]5
      hydroxytryptamine binding sites was very similar in the brain of all species
      investigated; densest labelling was observed in the globus pallidus, substantia
      nigra and superior colliculus. In all species, 5-carboxamidotryptamine competed
      for the labelled sites in a biphasic manner and metergoline displayed a
      subnanomolar affinity. In contrast, the beta-adrenoceptor blocking agents (
      )propranolol, (-)pindolol, and (+/-)SDZ 21009 were potent displacers only in the
      rat, hamster and opossum brains. These data indicate that non 5-HT1A/5-HT1C[3H]5
      HT binding sites display a high affinity for these agents in a particular rodent
      suborder as well as in opossum, a phylogenetically unrelated species.

PMID- 1361247
TI  - Chronic treatment with sabeluzole protects cultured rat brain neurons from the
      neurotoxic effects of excitatory amino acids.
AB  - The neuroprotective properties of the cognitive enhancer sabeluzole were
      investigated in rat brain neuronal cultures derived from the hippocampal
      formation of 17-day-old rat embryos. Measurement of the neuronal cytoskeletal
      microtubule-associated protein, MAP2, was used to assess survival of neurons
      after exposure of neuronal cultures to glutamate. MAP2 was quantified in neuronal
      cell homogenates by means of an enzyme-linked immunosorbent assay (ELISA) using a
      mouse monoclonal MAP2 antibody, peroxidase-labeled goat anti-mouse Ig antiserum,
      and 2,2'-azido-di-[3-ethylbenz-thiazoline] sulphonate (ABTS) as substrate.
      Exposure of 7-day-old neuronal cultures to 1 mM glutamate for 16 hours led to a
      three-fold increase in released lactate dehydrogenase (LDH) and a 40% decrease in
      cellular MAP2 content. Acute treatment of neuronal cultures with 10 microM
      sabeluzole yielded a 40% drop in released LDH induced by glutamate. Cultures
      treated chronically with 0.1 microM sabeluzole on days 1 and 4 in culture showed,
      after 1 week in culture, a MAP2 content and total LDH activity that was not
      different from control cultures. A 16-hour exposure to 1 mM glutamate did not
      induce LDH release or changes in MAP2 levels in sabeluzole-treated cultures. A
      single treatment with 0.1 microM sabeluzole between day 1 to 5 induced a 70-80%
      drop in glutamate-induced released LDH in 7-day-old neuronal cultures. Full and
      partial neuronal protection after chronic sabeluzole treatment at 0.1 microM was
      also observed for neurotoxicity induced by 5 mM N-methyl-D-aspartate (NMDA) and 1
      mM kainic acid or 30 microM veratridine, respectively. Within a series of
      compounds such as Ca++ and Na+ channel antagonists, glutamate receptor
      antagonists and various neurotransmitter receptor antagonists, sabeluzole,
      chronically given, were the most potent for inhibition of released LDH induced by
      1 mM glutamate (IC50-value: 34 +/- 13 nM). In conclusion, chronic sabeluzole
      treatment protects cultured rat brain neurons from excitotoxic aggression.

PMID- 1361248
TI  - Interaction of amfonelic acid with antipsychotic drugs on dopaminergic neurons.
AB  - The effects of two inhibitors of dopamine (DA) reuptake, amfonelic acid and GBR
      12909, on the clozapine- and haloperidol-induced increases in DA synthesis,
      release, and metabolism were investigated in the rat. In the striatum, as well as
      in the nucleus accumbens, the haloperidol-induced increase in tissue
      concentrations of dihydroxyphenylacetic acid (DOPAC) or the accumulation of
      dihydroxyphenylalanine (DOPA) was potentiated or unaltered, respectively, in rats
      treated with amfonelic acid. In contrast, amfonelic acid attenuated the
      stimulatory effects of clozapine on DOPAC concentrations and DOPA accumulation in
      both brain regions. GBR 12909 also differentially affected the haloperidol- and
      clozapine-induced increases in DOPAC concentrations. However, the clozapine
      induced increase in DOPA accumulation in the median eminence was not
      significantly altered by treatment with amfonelic acid. The haloperidol-induced
      increase in the extracellular concentrations of DA and DOPAC in the striatum also
      was potentiated by amfonelic acid, whereas the increase elicited by clozapine was
      suppressed. The increase in extracellular DA produced by the administration of
      morphine or the coadministration of ritanserin, a 5-HT2 antagonist, and
      haloperidol also was potentiated by amfonelic acid. The ability of amfonelic acid
      to distinguish between the actions of clozapine and haloperidol on nigrostriatal
      and mesocorticolimbic DA neurons does not appear to be related to differences in
      the effects of the drugs on DA autoreceptors or 5-HT2 receptors. Moreover, the
      mechanism through which clozapine activates tuberoinfundibular DA neurons may
      differ from that which is involved in the activation of nigrostriatal or
      mesocorticolimbic DA neurons.

PMID- 1361249
TI  - BMY-14802, a sigma ligand and potential antipsychotic drug, reverses amphetamine
      induced changes in neostriatal single-unit activity in freely moving rats.
AB  - The effects of BMY-14802 (5, 10, or 20 mg/kg), a sigma-receptor ligand showing
      preclinical evidence of antipsychotic efficacy, were tested on single-unit
      activity in the neostriatum of freely moving rats with or without pretreatment
      with 1.0 mg/kg D-amphetamine. Relative to resting baseline, amphetamine activated
      the large majority of neurons that changed firing rate in close temporal
      association with movement. All doses of BMY-14802 reversed this neuronal
      response, but the effect was most pronounced at 20 mg/kg. This dose, however, was
      equally likely to reverse or to induce a haloperidol-like potentiation of those
      neurons inhibited by amphetamine. In contrast, 10 mg/kg BMY-14802 consistently
      reversed amphetamine-induced neuronal inhibitions. All doses of BMY-14802
      attenuated the locomotor effects of amphetamine, but only the higher doses also
      blocked other aspects of the amphetamine behavioral response. By itself, BMY
      14802 dose dependently inhibited motor-related neurons, but elicited less
      behavioral activation than amphetamine. BMY-14802 (20 mg/kg) also induced
      hindlimb ataxia and occasional backwards locomotion. Haloperidol (1.0 mg/kg)
      reliably suppressed both behavior and neuronal activity when injected 30 min
      after BMY-14802, whether or not amphetamine pretreatment was given. Thus, BMY
      14802 shares with other neuroleptics the capacity to reverse amphetamine-induced
      excitations of neostriatal motor-related neurons, whereas other effects of BMY
      14802 reveal some haloperidol-like actions at 20 mg/kg that do not occur at lower
      doses.

PMID- 1361251
TI  - Evidence that lymphocyte traffic into rejecting cardiac allografts is CD11a- and
      CD49d-dependent.
AB  - Acute cardiac allograft rejection is characterized by infiltration of leukocytes
      into tissue parenchyma, but the site of entry and endothelial adhesion molecules
      involved are not yet defined. Lymphocyte binding to frozen sections prepared from
      day-3 rejecting cardiac allografts was significantly increased compared with
      sections made from normal hearts (number of bound lymphocytes, 983 +/- 216 per
      mm2 vs. 309 +/- 121, respectively, P < 0.001) or syngeneic grafts. The bound
      lymphocytes were located exclusively only on the top of the capillary structures
      and not on any other sites on the heart vasculature. We further wanted to analyze
      which of the cloned endothelial adhesion molecules and their counterreceptors
      would be involved in the increased lymphocyte binding. Lymphocyte pretreatment
      with mAb anti-CD11a or anti-CD49d inhibited this binding more than 50%. This
      inhibition on lymphocyte binding could not be increased by combining these two
      antibodies. Lymphocyte binding to endothelium has been shown to be at least
      partly organ specific; therefore, we asked whether increased lymphocytes adhere
      to cardiac allografts could be organ specific. Lymphocyte binding to lymph node
      high endothelial venules (HEV) has been shown to be inhibited by mannose-6
      phosphate (M6P) and to kidney peritubular capillaries by mannose-1-phosphate
      (M1P). In the present study neither of these carbohydrates had any effect on
      lymphocyte binding to cardiac allograft endothelium. Monosaccharide inhibition
      studies demonstrate that the mechanism of lymphocyte adhesion to cardiac
      capillary endothelium differs from adhesion to kidney allografts or peripheral
      lymph node high endothelium.

PMID- 1361250
TI  - Failure of salmeterol to inhibit circulating white cell responses and
      bronchoconstriction induced by platelet activating factor.
AB  - BACKGROUND: Platelet activating factor (PAF) is a potent mediator of
      inflammation. Inhalation of PAF causes acute bronchoconstriction and a transient
      fall in white blood cell count in humans. Salmeterol inhibits pulmonary
      inflammation induced by PAF in guinea pigs. METHODS: The effect of salmeterol on
      effects induced by PAF was investigated in eight normal subjects who inhaled
      salmeterol (50 micrograms) twice daily or a matched placebo for one week before
      challenge with PAF. Blood samples were taken from a forearm catheter for total
      white cell and neutrophil counts before and for 30 minutes after administration
      of PAF (48 micrograms) through a Mefar dosimeter. Blood films were stained for
      unsegmented neutrophils before and after treatment with PAF on a placebo day.
      RESULTS: Mean baseline total white cell counts and neutrophil counts did not
      differ on the two days. Mean baseline sGaw was significantly higher after inhaled
      salmeterol (1.84 (95% C1 1.45-2.23) s-1kPa-1) than after placebo (1.53 (1.24
      1.82)). After placebo mean total white cell counts, neutrophil counts, and sGaw
      were reduced to 60 (43-78)%, 39 (14-64)%, and 82 (71-93)% of baseline
      respectively five minutes after inhaled PAF. After salmeterol treatment mean
      reductions five minutes after inhaled PAF were 59 (45-73)%, 40 (19-61)%, and 82
      (71-93)% of baseline respectively. At 30 minutes after treatment with PAF the
      neutrophil count rebounded to 143 (82-204)% of baseline after placebo and to 127
      (93-161)% after inhaled salmeterol. There was no significant difference in the
      percentage of immature neutrophils before and after treatment with PAF (2.0 (0.5
      2.6)% compared with 3.9 (2.2-5.6)%. CONCLUSIONS: Treatment with salmeterol did
      not inhibit reduction in total white cell count or neutrophil count, rebound
      neutrophilia, acute bronchoconstriction, or transient flushing after inhalation
      of PAF. These results conflict with the inhibitory effect of salmeterol on lung
      inflammation in guinea pigs but are consistent with the lack of effect of
      salbutamol in humans. Salmeterol does not have an anti-PAF effect in vivo in
      humans.

PMID- 1361252
TI  - Novel immunohistochemical markers of human renal allograft dysfunction-
      antithrombin III, Thy-1, urokinase, and alpha-smooth muscle actin.
AB  - We have studied the expression of alpha-smooth muscle actin (alpha sm-1) by
      mesangial cells, and the expression of Thy-1 glycoprotein, antithrombin III
      (ATIII), and urokinase by tubular epithelial cells in normal kidneys and
      dysfunctional renal allografts. Kidney biopsies were studied immunocytochemically
      for changes in each of these markers and the findings were classified into two
      groups and compared with creatinine plasma levels at the time the biopsies were
      taken. In dysfunctional grafts, mesangial alpha sm-1 and tubular epithelial Thy-1
      reactivities were greatly diminished, and urokinase and ATIII were missing from
      proximal renal tubular epithelial cells. Urokinase, which was absent from normal
      renal glomeruli, appeared in glomeruli of some dysfunctional allografts. The
      possible usefulness of these markers in patient evaluations was supported by our
      finding that the distribution of vinculin, fibronectin, myosin, actin B4, desmin,
      glomerular HLA-DR, and the tubular expression of CD15 remained unchanged. These
      data prompt us to suggest that the immunocytochemical localization and evaluation
      of alpha sm-1, Thy-1, ATIII, and urokinase in kidney allografts may be useful
      adjuncts in the assessment of function in renal allografts.

PMID- 1361254
TI  - 10th Anniversary of the Collaborative Transplant Study and 100,000 CTS
      Transplants. Proceedings. Heidelberg, Germany, May 10-13, 1992.

PMID- 1361253
TI  - Prolongation of rat pancreatic islet allograft survival by anti-CD2 monoclonal
      antibody treatment.

PMID- 1361255
TI  - Matching for HLA-DPB1 alleles in zero mismatched HLA-A, -B, and -DR renal
      transplants.

PMID- 1361256
TI  - Importance of HLA-DRB1 genotyping in cadaveric renal transplantation.

PMID- 1361258
TI  - Definition of HLA class II genotypes and phenotypes for matching solid organ
      donors and their recipients.

PMID- 1361257
TI  - Analysis of discrepancies between serologic and DNA-RFLP typing for HLA-DR in
      kidney graft recipients.

PMID- 1361259
TI  - Nonradioactive DNA/RFLP analysis for HLA DR and DQ allotypes.

PMID- 1361260
TI  - Confidence levels assigned to serologic HLA-DR typing predict DNA HLA-DR typing
      discrepancies.

PMID- 1361261
TI  - Reliability of HLA typing on peripheral blood lymphocytes in cadaveric organ
      donors and the impact of blank donor antigens on kidney graft survival.

PMID- 1361262
TI  - Lymphocyte populations in peripheral blood after kidney transplantation.

PMID- 1361263
TI  - Mitochondrial/cytoplasmic enzyme ratio for the diagnosis of acute rejection after
      liver transplantation: sensitivity and specificity.

PMID- 1361265
TI  - 1st International Congress of the Cell Transplant Society. Pittsburgh,
      Pennsylvania, May 31-June 3, 1992.

PMID- 1361264
TI  - Proliferating cell nuclear antigen immunostaining of the endothelial cells in
      lung transplantation.

PMID- 1361266
TI  - Rapid isolation of CD4 or CD8 T-cell subsets using the CEPRATE LC laboratory cell
      separation system.

PMID- 1361267
TI  - Effect of cytokines on "de novo" lipid synthesis and hormone secretion by
      isolated human islets.

PMID- 1361268
TI  - The role of T cells in the destruction of xenografts within cell-impermeable
      membranes.

PMID- 1361269
TI  - Proliferation and differentiation of fetal liver cells transplanted into rat
      spleen.

PMID- 1361270
TI  - Effect of selective donor T-cell depletion on the graft-versus-leukemia reaction
      in allogeneic marrow transplantation.

PMID- 1361271
TI  - Cell transplantation for Huntington's disease.

PMID- 1361272
TI  - 6th Scientific Meeting of the Latin American Transplantation Society. Porto
      Alegre, Brazil, September 18-21, 1991.

PMID- 1361273
TI  - Immobilization of mink (Mustela vison) with medetomidine-ketamine and
      remobilization with atipamezole.
AB  - Four groups of mink were immobilized with medetomidine-HCl (MED) 0.1 mg/kg +
      ketamine (KET) 5 or 7.5 mg/kg at different ambient temperatures. The induction
      time, degree of immobilization and analgesia, rectal temperature, heart and
      respiration rates were recorded at intervals throughout the immobilization
      period. The animals were then given atipamezole-HCl (ATI) 0.5 mg/kg for reversal
      at different times after injection of MED/KET and the effects of the antagonist
      were evaluated. Subcutaneous administration of MED/KET induced complete
      immobilization in all 20 animals, and the highest dose was considered suitable
      for major surgery. Prolonged immobilization at low ambient temperatures (-10 to
      +5 degrees C) caused severe hypothermia in all animals. The mean rectal
      temperature had dropped to 37.8 degrees C and 32.1 degrees C at 15 and 85 min,
      respectively, after injection of MED/KET, significantly lower than the
      corresponding values for animals immobilized at room temperature. Intramuscular
      administration of ATI 20 or 40 min after injection of MED/KET rapidly remobilized
      the animals without apparent side-effects. Administration of ATI to animals
      recovering spontaneously 90 min after injection of MED/KET induced thermogenesis
      (shivering) in animals immobilized at a low ambient temperature, while no such
      effect was seen in animals immobilized at room temperature. One hour after
      injection of ATI, the rectal temperatures of all treated animals had returned to
      normal and there were no signs of abnormal behaviour.

PMID- 1361274
TI  - Value of ambulatory blood pressure recordings.
AB  - In the present paper, the value of ambulatory blood pressure recordings is
      discussed. Such recordings can be very helpful in the management of high and low
      blood pressure. The fact that more readings are obtained and that they are made
      in normal life conditions are the strongest arguments in favour of those
      recordings. Whether ambulatory recordings predict long term prognosis better than
      office blood pressure is still open for discussion; the long term European study
      OvA should help clarifying this important question. Data coming from these
      techniques are especially useful when conflicting elements are present such as
      high pressure with no organ damage or blood pressure resistant to all drugs and
      side effects occurring with even minor doses of antihypertensive drugs. Short
      term episodes of high or low pressure are best documented with ambulatory blood
      pressure recordings and this holds particularly true in patients with arterial
      hypotension. Finally several research aspects can be approached by ambulatory
      recordings of pressure such as the study of pharmacokinetics of drugs and
      analysis of blood pressure variability.

PMID- 1361275
TI  - The enigma of cyclosporin A treatment for psoriasis: systemic efficacy versus
      topical non-responsiveness. A review.

PMID- 1361276
TI  - The increase in skin hydration after application of emollients with different
      amounts of lipids.
AB  - Emollients can increase the water content in the stratum corneum by delivery of
      their water to the skin, and by occlusion. These two mechanisms were studied
      using three preparations with different concentrations of lipids. The products
      were applied to the skin and then removed by cleaning the surface after 5 and 40
      min. The increase in skin water loss following removal of product residue was
      considered as a release of excess water in the skin. Exposure of the skin to pure
      petrolatum for 5 min gave no increase in the water loss from the skin surface
      following removal of the product residue. A lipid rich cream (66% lipids) gave a
      significant increase, but the highest increase was found after removal of an
      ordinary cream (27% lipids). Release of water from the skin indicates that water
      in the creams had previously been absorbed into the skin. The occluding
      properties of the products were determined after 40 min of exposure. Petrolatum
      reduced the water loss by approximately 50% and the other products by 16%. The
      occlusion caused an increase of water in the skin, which resulted in a release of
      water following removal of the products. The release was related to the reduction
      of water loss. Thus petrolatum gave a higher release of water than the other
      emollients.

PMID- 1361277
TI  - Interleukin-8 receptors in normal and psoriatic polymorphonuclear leukocytes.
AB  - Polymorphonuclear leukocyte (PMNL) infiltration is an important characteristic in
      psoriatic lesions. The proinflammatory 8-kD peptide interleukin-8 (IL-8) is
      present in psoriatic scales and possesses a high chemotactic activity on human
      neutrophils, which may relate to its role in psoriasis. Its chemotactic activity
      is mediated via specific receptors on PMNL. The goal of our work was to ascertain
      whether PMNL infiltration in psoriasis can be accounted for by functional
      abnormalities of the circulating PMNL due to alterations in the IL-8 receptor
      density or affinity (or both). Results of radioligand binding studies performed
      in 10 psoriatic patients, 10 patients with atopic eczema and 11 normal controls
      showed no difference in receptor affinity (Kd) between the groups. However, a
      slight but significant elevation in IL-8 receptor density was seen on PMNL from
      psoriatic individuals (31,230 +/- 3,237 binding sites per cell) compared to those
      from normal volunteers (24,152 +/- 2,643) and atopic eczema patients (24,092 +/-
      2,743). Increased number of IL-8 receptors may, besides elevated cutaneous IL-8
      concentrations, contribute to the intraepidermal accumulation of PMNL in
      psoriasis.

PMID- 1361278
TI  - A new marker of epidermal differentiation associated with the membrane coating
      granules: characterization and applications to pathology.
AB  - A murine monoclonal antibody, BC12, was obtained after immunization against
      suprabasal human keratinocytes. In the epidermis of normal human skin, the
      antigen recognized by BC12 (BC12 antigen) is located at the apex of keratinocytes
      in the upper stratum spinosum and stratum granulosum but is absent in other
      layers. The BC12 antigen is also present in hair follicles. Immunoblotting
      performed on keratinocyte subpopulations confirmed the presence of the BC12
      antigen in differentiated keratinocytes only. Two-dimensional immunoblotting
      showed that the BC12 antigen corresponds to a set of polypeptides with an
      apparent molecular weight of approximately 33kD. In keratinocyte cultures, the
      antigen is present only in stratified areas. The distribution of the BC12
      antigen, as studied by indirect immunofluorescence and immunoelectron microscopy,
      and its presence in certain subcellular fractions of epidermal cells suggest that
      it is a component of membrane coating granules (MCGs) or that it is associated
      with these structures. Strikingly, in psoriasis, eczema and many other diseases,
      the BC12 antibody does not label the epidermis, but vessels in dermal papillae.
      The BC12 antibody may thus be a useful tool in the study of keratinocyte
      differentiation and MCG physiology, and, also, in pathology.

PMID- 1361279
TI  - Immunophenotypical characterization of inflammatory cellular infiltrates in
      tinea.
AB  - In order to elucidate the still poorly understood pathogenetic pathways of acute
      tinea, the inflammatory cellular infiltrates in this infection were analyzed.
      Lesional punch biopsies were cryostat-sectioned and stained with monoclonal
      antibodies for immunophenotypization of T cells, B cells, macrophages and
      activation markers. For each antibody the positively stained inflammatory cells
      in the dermis and in the epidermis were quantified separately. Most of the dermal
      mononuclear cells in acute tinea were identified as T helper lymphocytes of the
      memory type. Furthermore, considerable amounts of Langerhans' cells and
      macrophages were found, but virtually no B cells. A high proportion of cells
      expressed markers of activation. Within the epidermis, accumulations of
      Langerhans' cells and LeuM5+ dendritic macrophages were detected near fungal
      element. In view of the otherwise rather similar cellular infiltrates in acute
      tinea and different non-infectious dermatoses, acute tinea may be particularly
      suitable to study the functional relationship of Langerhans cells and LeuM5+
      macrophages.

PMID- 1361280
TI  - Quantitative analysis of Langerhans' cells in epidermis at irritant contact
      reactions using confocal laser scanning microscopy.
AB  - Confocal laser scanning microscopy (CLSM) was used for quantitative analysis of
      CD1a+ cells in epidermis at irritant reactions. Sodium lauryl sulphate (2% and
      4%) or non-anoic acid (20% and 80%) were applied to the skin of healthy
      volunteers under occlusion for 24 h. Skin biopsy specimens were taken after
      additional 24 h and were snap frozen. Freeze-sections, 25 microns thick, were
      stained with anti-CD1a antibodies (Leu-6) followed by FITC-labelled rabbit anti
      mouse IgG. The sections were viewed and optically sectioned in the CLSM at four
      depth levels. The data was analysed using a threshold value for the fluorescence.
      The obtained result is presented as the proportion of specimen area having a
      fluorescence intensity above the threshold. The result demonstrates that the CLSM
      is a useful tool for obtaining not only structural information but also
      quantitative information from a defined tissue volume. In the present
      investigation it was possible to demonstrate variations in CD1a+ reactivity in
      epidermis at detergent-induced irritant reactions with a marked decrease in CD1a+
      after 80% non-anoic acid exposure and only minor differences in the CD1a+ after
      2% and 4% sodium lauryl sulphate exposure.

PMID- 1361281
TI  - Comparison of muscle-derived serum carbonic anhydrase III and myoglobin in
      dermatological patients: effects of isotretinoin treatment.
AB  - The serum levels of muscle-specific serum carbonic anhydrase III (S-CAIII) and
      myoglobin (S-Myo) were analyzed in various male dermatological patients of the
      same age. The mean levels of S-CAIII and S-Myo were essentially similar in
      patients with acne, psoriasis vulgaris, atopic eczema and tinea, suggesting that
      common dermatological diseases do not affect the serum levels of the muscle
      markers. Increased levels of S-CAIII, which is specific for skeletal muscle
      cells, were found in the acne patients who had been treated with isotretinoin.
      However, when S-CAIII and S-Myo were studied in 24 patients (16 males, 8 females)
      before and during isotretinoin treatment, no constant increases in these markers
      could be observed. When individual patients were followed for several months,
      transient increases or decreases could be observed. The changes in S-CAIII, or S
      Myo, did not correlate with the dose of isotretinoin, nor with the duration of
      the treatment. The results suggest that systemic isotretinoin does not
      specifically affect skeletal or myocardial muscles. The increases in these
      markers observed in the course of dermatological diseases and isotretinoin
      treatment are obviously due to other factors, such as exercise.

PMID- 1361282
TI  - Sequential concentration of chloroquine in human hair correlates with ingested
      dose and duration of therapy.
AB  - Human scalp hair was analyzed for chloroquine using gas-chromatography. In 5
      patients it was demonstrated that the amount of uptake of chloroquine into the
      hair varied proportionally with the dosage (from 500 mg/week to 10 g single dose)
      and with the time of administration. The chloroquine concentrations ranged from 8
      to 1100 micrograms/g hair. Chloroquine could be determined quantitatively after a
      single toxic dosage used in a suicidal attempt and also after low therapeutic
      doses. The sequential examination of the hair shaft allows an assessment of the
      chloroquine amount taken over time, the individual dosage, the initiation and
      termination of therapy. As hairs can be collected easily, they are a unique
      specimen for investigation, and it is suggested that they can virtually be used
      as a "tachogram" of chloroquine drug-therapy or intoxication.

PMID- 1361283
TI  - Lichenoid eruption induced by low dose captopril.
AB  - A patient with congestive cardiac failure developed a rash following captopril
      treatment. The clinical and histological features were consistent with a
      lichenoid eruption. The rash spontaneously resolved without any treatment three
      months after captopril was discontinued.

PMID- 1361285
TI  - Methotrexate hepatotoxicity in psoriatic patients submitted to long-term therapy.
AB  - Eighty-four patients with severe psoriasis who required methotrexate (MTX)
      therapy have been reviewed. A total of 134 liver biopsies were performed. The
      lack of correlation between alcohol intake and the use of potential hepatotoxic
      drugs with pretreatment liver biopsies is noted. A review of 30 patients who had
      liver biopsies performed before and after MTX treatment showed no statistically
      significant difference between the histological grades before and after
      treatment. Nor was there any absolute correlation between the cumulative MTX
      doses and the histological changes of follow-up biopsies. In this group of
      patients, 15 (50%) developed fibrosis, which was severe in 2 patients, after
      3,431 mg MTX average dose. Cirrhosis was observed in 3 patients (10%) after 1,667
      mg MTX average dose. Follow-up liver biopsies are recommended for patients
      treated with MTX.

PMID- 1361284
TI  - Pityriasis alba in a psoriatic location.
AB  - Three patients with pityriasis alba whose lesions were confined to the knees only
      are reported. Such cases can be misdiagnosed as psoriasis. The key to the correct
      diagnosis lies in the physician's awareness of the existence of this variant of
      pityriasis alba.

PMID- 1361286
TI  - Elimination diet in young children with atopic dermatitis.
AB  - Thirteen children with severe current atopic dermatitis unresponsive to topical
      treatment were started on an elimination diet. One child was excluded because she
      could only keep to the diet for 3 days. Twelve children aged 0.8-4.1 years
      maintained the diet for 2-4 weeks. In six children the dermatologist's score
      showed a clear improvement while on diet, in 2 children there was a minor
      improvement and in 4 children the dermatologist's score did not change during
      elimination diet. Challenges were performed with egg, milk and wheat in 6
      children and with milk and wheat in 2 children. The challenges were done in an
      open way except for the dermatologist, who was unaware of which food the child
      had received. No child in the study had an immediate reaction but 3 children had
      late reactions, one after egg, one after milk and one child after challenge with
      wheat.

PMID- 1361287
TI  - Interferon-alpha therapy in atopic dermatitis.
AB  - Thirteen patients with a severe adult form of atopic dermatitis (AD) received 3.0
      x 10(6) IU of recombinant interferon-alpha 2a (rIFN-alpha 2a) 3 times a week. A
      satisfactory response was obtained in 5 of them. Serum IgE levels in all 13
      patients remained unchanged throughout the study. Flu-like symptoms were common,
      but clinical or laboratory adverse effects were otherwise slight. The moderately
      beneficial therapeutic effects observed in this study support a possible role for
      IFN-alpha in controlling immunologic deficiencies in atopic dermatitis.

PMID- 1361288
TI  - The genetic risk for alopecia areata in first degree relatives of severely
      affected patients. An estimate.
AB  - Substantial evidence indicates that genetic factors may have a role in the
      etiology of alopecia areata (AA). Most studies, however, provide only general
      information on the familial incidence but fail to specify family relationships.
      We therefore obtained information on the incidence of AA in first degree
      relatives of 348 severely affected patients. In 7% one of the parents was
      affected. Among the siblings of the patients 3% had developed AA, while AA was
      present in 2% of the children. Taking into account the age of the children, their
      lifetime risk was calculated to approach 6%. However, a severe type of AA is to
      be expected only in about 2% of the children. The degree of involvement observed
      in the patients did not influence the frequency and type of AA present in their
      first degree relatives.

PMID- 1361289
TI  - A new case of Zimmermann-Laband syndrome with atypical retinitis pigmentosa.
AB  - This paper reports a case study of a 10-year-old girl exhibiting symptoms of a
      Zimmermann-Laband syndrome (ZLS), including an ocular involvement not previously
      observed. In addition to the case reported, we have also discovered 21 patients
      described in the literature. Major clinical findings, defined as being present in
      more than 75% of the cases under discussion, are presented.

PMID- 1361290
TI  - The relation between lichen planus and hepatitis C: a case report.
AB  - A case of simultaneous occurrence of lichen planus (LP) and hepatitis C in the
      same patient is presented. The patient had received treatment with interferon
      alpha for her chronic liver disease, and the association between LP, hepatitis C
      and interferon alpha treatment is discussed.

PMID- 1361291
TI  - Dupuytren's contracture (palmar fibromatosis) extending over the arm.

PMID- 1361292
TI  - Adjuvant treatment of recalcitrant genitoanal warts with systemic recombinant
      interferon-alpha-2c.
AB  - Seventeen male patients with recalcitrant genitoanal warts, who had been
      unsuccessfully treated with classical destructive modalities for 16 months on
      average, were included in an open uncontrolled trial. The treatment regimen
      consisted of caustic and/or surgical measures as judged optimally suited in the
      individual cases, combined with an intermittent systemic low-dose adjuvant
      interferon-alpha-2c regimen (3 or 6 5-day-courses with intervals of 2 weeks)
      followed by a 1-year-observation period. At the end of interferon treatment, no
      patient had clinically visible warts but 10 still had subclinical acetic acid
      positive lesions. At the end of the 1-year-observation period, clearance of both
      warts and acetowhite lesions was observed in 4 patients (23.5%), whereas
      acetowhite lesions persisted in 4 others (23.5%). Recurrence of clinically
      visible lesions, always within the acetowhite areas, was observed in 9 (53%)
      patients. Interferon may thus have been effective in suppressing clinical
      recurrences of genitoanal warts, but its potency to eradicate subclinical
      papillomavirus infection was disappointing.

PMID- 1361293
TI  - The route of rapid access of drugs to the distal nail plate.
AB  - It has recently been shown that antimycotic drugs have unexpectedly rapid access
      to distal nail, which we have suggested occurs through the site of continuous
      ventral nail formation along the nail bed. To exclude the alternative possibility
      of diffusion through the nail plate, we have measured the effect of topical
      terbinafine cream in onychomycosis. Sustained outward movement of the fungally
      affected distal segment was seen in only 2 of 10 measured nails, and there was no
      change in the mean severity of clinical involvement in 53 nails under study. This
      excludes significant diffusion of drugs through the nail plate, and we conclude
      that the route of rapid access is indeed through the nail bed.

PMID- 1361295
TI  - Psoriasis: a disease of a thousand key words.

PMID- 1361294
TI  - Chronic aquagenic urticaria.

PMID- 1361296
TI  - General pustular psoriasis: pathogenetic relationship between pustule and
      epidermal sweat duct.

PMID- 1361297
TI  - Reticulate hyperpigmentation of Iijima, Naito and Uyeno and other linear
      hyperpigmentations of children.

PMID- 1361298
TI  - E rosette formation in B cell chronic lymphocytic leukemia.
AB  - We describe a patient with B cell chronic lymphocytic leukemia whose B
      lymphocytes showed the capacity to form rosettes with sheep red blood cells
      during prolymphocytoid transformation of the disease. In this case, rosette
      formation was found to be related to the presence of the classic E rosette
      receptor since the leukemic cells were recognized by the OKT11 monoclonal
      antibody. This feature was not shown at diagnosis. Evaluation of this phenomenon
      is discussed.

PMID- 1361299
TI  - Recent progress on kinins. Biochemistry and molecular biology of the kallikrein
      kinin system. Proceedings of the International Conference "Kinin 91 Munich".
      Munich, September 8-14, 1991.

PMID- 1361300
TI  - Aminopeptidase P: purification of a membrane-bound bradykininase from rat lung.
AB  - Aminopeptidase P that hydrolyzes the Arg1-Pro2-bond of bradykinin was solubilized
      from rat lung microsomes using phosphatidylinositol-specific phospholipase C. The
      enzyme was purified 420-fold by chromatography on decylagarose (two steps), omega
      aminodecyl-agarose and DEAE-Sephacel. A single stained band was observed
      following native gradient (4-15%) polyacrylamide gel electrophoresis.
      Dipeptidylaminopeptidase IV-like activity was also present in the final
      preparation and co-migrated with aminopeptidase P in the above gel system.

PMID- 1361301
TI  - Immunolocalization of high molecular weight kininogen (HKg) and T kininogen (TKg)
      in the rat hypothalamus.
AB  - Specific HKg immunostaining detected with antiserum against the light chain (LC)
      of HKg was restricted to SRIF neurons of the hypothalamic periventricular area
      projecting to median eminence (ME). Heavy chain (HC) immunoreactivity related to
      HKg and/or low molecular weight kininogen (LKg) was found in some other
      hypothalamic territories. Specific TKg was mainly associated with vasopressin in
      neurons of suprachiasmatic (SCN), supraoptic (SON) and paraventricular (PVN)
      nuclei. By direct RIA, hypothalamus was found to contain the highest level of TKg
      (10ng/mg protein) and after trypsin hydrolysis and HPLC separation of kinins,
      10.3 pg BK and 7.3 pg T-kinin/mg protein.

PMID- 1361302
TI  - Beta-blocker therapy in acute myocardial infarction: evidence for
      underutilization in the elderly.
AB  - PURPOSE: To assess the impact of patient age on the use of beta-blocker therapy
      in the management of acute myocardial infarction. PATIENTS AND METHODS: The
      population studied consisted of 4,762 patients hospitalized with validated acute
      myocardial infarction in 16 hospitals in the Worcester, Massachusetts, Standard
      Metropolitan Statistical Area during the years 1975, 1978, 1981, 1984, 1986, and
      1988. Logistic regression analysis was employed to control for relevant
      demographic and clinical variables in evaluating the independent effect of
      patient age as a determinant of receipt of beta-blocker therapy during the
      hospitalization. RESULTS: A consistent trend toward reduced use of beta-blocker
      therapy in older patients was demonstrated. After adjustment for demographic and
      clinical variables (gender; prior history of angina, hypertension, or diabetes
      mellitus; myocardial infarction characteristics; complications including
      congestive heart failure and shock; and use of digoxin and diuretics), odds
      ratios for receipt of beta-blocker therapy relative to patients less than 55
      years of age were 0.61 for those 55 to 64; 0.52 for those 65 to 74; 0.36 for
      those 75 to 84; and 0.26 for those 85 or older. Analyses performed for each study
      year demonstrated results consistent with those for the overall study population.
      CONCLUSION: The results of this population-based study suggest that there are
      substantial opportunities for expanded use of beta-blocker therapy in elderly
      patients who have sustained an acute myocardial infarction.

PMID- 1361303
TI  - Resolution of HIV retinitis with zidovudine therapy.

PMID- 1361304
TI  - Reversible hepatic injury induced by long-term vitamin A ingestion.

PMID- 1361305
TI  - Methadone and immune function.

PMID- 1361308
TI  - Fiber-optic ammonia sensor for measuring synaptic glutamate and extracellular
      ammonia.
AB  - A fiber-optic ammonia gas sensor designed for neurochemical applications is
      presented. Parameters evaluated in terms of effect on the steady-state and
      dynamic response of this sensor include the indicator dye, concentrations of
      indicator and total ammonia nitrogen in the internal solution, volume of the
      internal solution, structure of the gas-permeable membrane, and temperature. The
      final ammonia sensor responds over the concentration range from 7 to 3000 nM with
      a limit of detection of 7 nM and response times ranging from 2 to 5 min.
      Glutamate oxidase is immobilized at the tip of this ammonia sensor to provide a
      glutamate biosensor with a detection limit of 0.1 microM when operated at pH 7.8.
      In addition, this ammonia sensor is used to measure extracellular ammonia levels
      in perfused retinal and eye-cup tissue preparations. These measurements indicate
      a calcium-dependent, potassium-evoked release of ammonia during these
      depolarization conditions.

PMID- 1361307
TI  - Rapid screening for taxanes by tandem mass spectrometry.
AB  - A highly specific and sensitive method is described for determining taxol,
      cephalomannine, and baccatin III in crude plant extracts. Radical anions of the
      taxanes are formed by desorption chemical ionization, and a parent tandem mass
      spectrometric scan is used to recognize these compounds by their characteristic
      dissociations. The limit of detection of the individual taxanes in typical plant
      matrices is less than 500 pg when all three species are screened simultaneously.
      Because of the sensitivity of the method, extraction times can be shortened to 30
      min and crude extracts can be examined at the rate of 6/h. Detection of all three
      taxanes extracted from a single Taxus cuspidata needle in a combined
      extraction/analysis time of less than 1 h is demonstrated.

PMID- 1361306
TI  - Growth fraction in non-small cell lung cancer estimated by proliferating cell
      nuclear antigen and comparison with Ki-67 labeling and DNA flow cytometry data.
AB  - Results generated by the immunohistochemical staining with PC10, a new monoclonal
      antibody recognizing PCNA (a nuclear protein associated with cell proliferation)
      in formalin-fixed and paraffin-embedded tissue were compared with those of Ki-67
      labeling and DNA flow cytometry in 47 consecutive non-small cell lung cancer
      (NSCLC). PCNA reactivity was observed in all samples and confined to the nuclei
      of cancer cells. Its frequency ranged from 0 to 80% (37.7 +/- 23.6) and larger
      sized, early-staged and DNA aneuploid tumors expressed a significant higher
      number of PCNA-reactive cells. The PCNA and Ki-67 labeling rates were closely
      correlated (r = 0.383, P = 0.009). By flow cytometry, we observed a good
      correlation among PCNA labeling and S-phase fraction (r = 0.422, P = .0093) and
      G1 phase (r = 0.303, P = .051) of the cell cycle. Results indicate that PCNA
      labeling with PC10 is a simple method for assessing the proliferative activity in
      formalin-fixed, paraffin-embedded tissue of NSCLC and correlates well with Ki-67
      labeling and S-phase fraction of the cell cycle.

PMID- 1361309
TI  - Priming doses of atracurium and vecuronium depress swallowing in humans.
AB  - The administration of low doses of muscle relaxant may cause peripheral muscular
      weakness including difficulty in swallowing. In the present study, the effect of
      priming doses of atracurium and vecuronium on swallowing was studied. Sixty
      patients undergoing elective surgery under general anesthesia were divided
      randomly into four groups of 15 patients and received as a priming dose either
      vecuronium (10 or 15 micrograms/kg) or atracurium (50 or 75 micrograms/kg).
      Swallowing muscle activity was measured by electromyography using submental
      surface electrodes. Swallowing was initiated by administration of 0.3 ml
      distilled water through an oral catheter. Swallowing reflex was determined by
      measuring the latency time (i.e., time from water administration to start of EMG
      activity of glossal muscles). Swallowing activity was determined by integration
      of the EMG of glossal muscles during swallowing. Peripheral muscle strength was
      determined by hand grip strength. Swallowing reflex activity and peripheral
      muscle strength were measured before and 3 and 6 min after administration of
      vecuronium or atracurium. Latency time remained unchanged after any of the
      priming doses. Integrated EMG decreased significantly (P < .001) 3 and 6 min
      after all priming doses tested (42-75% of baseline value). Only after atracurium
      75 micrograms/kg was the hand grip strength significantly decreased (P < .01).
      These results suggest that owing to its effect on swallowing, the priming dose
      should be used with caution.

PMID- 1361310
TI  - Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and
      metabolic rate.
AB  - Dexmedetomidine (DMED) is a highly selective centrally acting alpha 2-adrenergic
      agonist thought to provide significant sedation without appreciable ventilatory
      effects. This double-blind, placebo-controlled experiment evaluated four dose
      levels of DMED (0.25, 0.5, 1.0, and 2.0 micrograms/kg intravenously over 2 min)
      in 37 healthy male volunteers. Measurements of sedation, arterial blood gases,
      resting ventilation, hypercapnic ventilatory response (HVR), and metabolic rate
      (O2 consumption and CO2 production) were performed at baseline, 10 min after DMED
      infusion, and thereafter at the end of each subsequent 45-min period. DMED caused
      sedation resulting in loss of responsiveness in most of the subjects administered
      1.0 and 2.0 micrograms/kg; sedation was evident for 195 min following 2.0
      micrograms/kg (P < .05). Ten minutes following infusion of 1.0 and 2.0
      micrograms/kg, PaCO2 had increased by 5.0 and 4.2 mmHg, respectively (P < .05),
      and 60 min following 2.0 micrograms/kg, VE had decreased by 28% (P < .05). The
      placebo group showed a progressive increase in the HVR slope (50% increase by 330
      min following the infusion; P < .05). Overall, across all the DMED doses, the
      slope was decreased (P < .05) at all times after DMED. The calculated ventilation
      at a PaCO2 of 55 mmHg was decreased (39%; P < .05) 10 min following 1.0 and 2.0
      micrograms/kg, returning to control values by 285 min following 2.0
      micrograms/kg. O2 consumption increased 16% (P < .05) at 10 min following 2.0
      micrograms/kg; CO2 production decreased (22% at 60 min). By 5 h postinfusion,
      both had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361311
TI  - Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes.
AB  - Dexmedetomidine (DMED) is a novel clonidine-like compound known to have sedative,
      analgesic, and cardiovascular stabilizing qualities. DMED is a more highly
      selective alpha 2-adrenergic agonist than clonidine. This investigation examined
      the hemodynamic effects of four selected iv doses in consenting healthy male
      volunteers. In a randomized, double-blind, placebo-controlled trial subjects
      received 0 (n = 9), 0.25 (n = 6) 0.5 (n = 6), 1.0 (n = 6), or 2.0 (n = 10)
      micrograms/kg of DMED by infusion (2 min). ECG, heart rate (HR), arterial blood
      pressure (MABP), bioimpedance cardiac output (CO), and plasma catecholamines
      concentrations (CA) were monitored from 90 min before to 360 min after infusion.
      Plasma DMED concentrations were measured. DMED produced a maximum decrease in
      MABP at 60 min of 14%, 16%, 23%, and 27% for the 0.25, 0.5, 1.0, and 2.0
      micrograms/kg groups, respectively (P < .05). At 330 min MABP remained below
      baseline by 8% and 17% at the two largest doses (P < .05). Both HR and CO
      decreased maximally by both 17% at 105 min. The two largest doses produced a
      transient (peak at 3 min lasting < 11 min) increased in MABP (16 +/- 2.5 and 24
      +/- 10 mmHg, respectively; P < .05) with a concomitantly reduced CO (41%, 2
      micrograms/kg; P < .05) and HR (22%, 2 micrograms/kg; P < .05), whereas systemic
      vascular resistance doubled. Even the lowest dose decreased CA immediately to
      values close to 20 pg/ml for 5 h. A 2-min iv infusion of DMED produced a
      transient increase in MABP and a longer lasting decrease in MABP and CA. These
      DMED doses were well tolerated in the healthy volunteers.

PMID- 1361312
TI  - Ketamine as a probe for medetomidine stereoisomer inhibition of human liver
      microsomal drug metabolism.
AB  - Medetomidine (MED) is a novel, selective, alpha 2 adrenergic agonist with potent
      sedative, hypnotic, and analgesic properties, currently undergoing evaluation as
      an anesthetic adjuvant. The pharmacologic effects of MED are stereospecific, due
      entirely to the D-isomer (DMED), whereas the L-isomer (LMED) is essentially
      inactive. DMED, a 4(5)substituted imidazole, has been shown to inhibit adrenal
      steroidogenesis and human liver microsomal alfentanil metabolism, reactions
      mediated by cytochrome P-450. The mechanism of MED inhibition of cytochrome P-450
      is unknown. The purpose of this investigation was to determine the mechanism of
      DMED inhibition of human cytochrome P-450-mediated microsomal metabolism, using
      ketamine as a probe. Ketamine undergoes extensive hepatic biotransformation and
      has been used previously to characterize the effects of imidazole anesthetics on
      human P-450-catalyzed drug metabolism. Ketamine N-demethylation by microsomes
      from three human livers was measured by gas chromatography-mass spectrometry with
      selected-ion monitoring. DMED was a potent, competitive inhibitor of S(+)
      ketamine N-demethylation, with a Ki of 0.11-0.18 microM for the high affinity
      ketamine demethylase. The IC50 for DMED inhibition of therapeutic concentrations
      of racemic ketamine (10 microM) was 0.15 +/- 0.02 microM. Preincubation of DMED
      with microsomes and an NADPH generating system prior to ketamine addition had no
      additional effect on the inhibition of ketamine demethylase activity, thereby
      implicating the parent compound rather than a DMED metabolite as the inhibitory
      species. LMED, although pharmacologically inactive, had a greater inhibitory
      effect than DMED on racemic ketamine and ketamine enantiomer demethylation at
      therapeutic concentrations. Spectral studies showed that DMED interacted with
      microsomal cytochrome P-450 to elicit a Type II binding spectrum.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1361313
TI  - Non-beta-adrenergic-mediated peripheral circulatory hyperkinesia in
      hyperthyroidism.
AB  - Systolic time intervals and brachial circulation, evaluated by pulsed Doppler in
      terms of arterial diameter, blood velocity and flow, and vascular resistance,
      were studied in 12 hyperthyroid patients and in 12 normal controls. In patients,
      arterial circulation was studied before and during mechanical exclusion of the
      hand, and hemodynamic measurements were repeated after beta-blocker treatment and
      after obtainment of euthyroid state. Compared with controls, patients had higher
      heart rate (P < 0.001), lower systolic time intervals (P < 0.05, P < 0.01), and
      higher blood velocity (P < 0.05). Beta blockade decreased heart rate (P < 0.05, P
      < 0.001) but did not change systolic time intervals and arterial circulation.
      Euthyroid state decreased heart rate (P < 0.01), preejection period (P < 0.01),
      and blood velocity (P < 0.01) and flow (P < 0.05). The decreases in velocity and
      flow before hand exclusion when euthyroid state was obtained were correlated with
      hyperthyroid values of velocity and flow respectively (r = 0.85, r = 0.90, P <
      0.01, P < 0.001). Vascular resistance during hand exclusion was correlated
      negatively with serum T3 level during hyperthyroid and euthyroid states. Thus,
      thyroid hormones but not beta-adrenoreceptors participate in the peripheral
      hyperkinesia of hyperthyroidism.

PMID- 1361314
TI  - Additive and synergistic pharmacologic inhibition of equine fibrinoligase (factor
      XIIIa*-like) biochemical activity.
AB  - A selected group of pharmaceutical compounds were evaluated for the ability to
      inhibit the biochemical activity of fibrinoligase (coagulation factor XIIIa*) in
      pooled equine plasma. Criteria for the pharmaceuticals selected were based on the
      mechanism of the transglutamination biochemical reaction mediated by coagulation
      factor XIIa*. These criteria were complemented by recognition of the molecular
      configuration and chemical composition of amino acid residue side chains involved
      in the process of covalent fibrin monomer polymerization (cross-linking,
      transglutamination) mediated by this enzyme. Each pharmaceutical was evaluated
      individually and in combination with other potential coagulation factor XIIIa*
      inhibitors in an effort to detect additive and synergistic phenomenon. In this
      context, pharmaceuticals with a carbonylamide (eg, cefuroxime, Girard's reagent
      P, prolinamide) were applied in concert with compounds with a terminal amine (eg,
      D-arginine, L-lysine) functional group. In concept, this method theoretically
      served to competitively simulate glutamine and lysine amino acid residues within
      strands of fibrin monomer substrate involved in phase I (carbonylamide) and phase
      II (terminal amine) of the transglutamination reaction (covalent fibrin monomer
      cross-linking). Halogen-dinitro and ethylene compounds were also evaluated
      because of their reported ability to inactivate enzyme systems dependent on an
      intact sulfhydryl group located at their biochemically active site (eg, cystine
      amino acid residue). This group of pharmaceutical compounds failed to inhibit the
      biochemical activity mediated by coagulation factor XIIIa* in equine plasma.

PMID- 1361315
TI  - Graded work exposure to promote work return after severe hand trauma: a
      replicated study.
AB  - Fifty-one patients with posttraumatic stress disorder after work-related hand
      injuries were placed on a graded work exposure program to facilitate return to
      work. These patients consisted of an initial group of 25 patients and a
      replication group of 26 patients. The program returned 92% of the initial group
      and 88% of the replicated group to work with their previous employers. At 6-month
      follow-up, 88% of the initial group and 80.1% of the replication group were still
      working full-time at the jobs to which they had returned. All of the patients not
      working with their previous employer at follow-up had appraisal/projected flash
      backs, which have previously been associated with a 90% failure to return to
      work. This intervention was successful with 73% of the patients experiencing such
      flashbacks. In conclusion, graded work exposure was an effective treatment to
      promote return to work for patients experiencing significant psychological
      symptomatology after severe hand injury.

PMID- 1361316
TI  - Polymorphism of class I alcohol dehydrogenase in French, Vietnamese and Niger
      populations: genotyping by PCR amplification and RFLP analysis on dried blood
      spots.
AB  - The polymorphism of human alcohol dehydrogenase (ADH) can contribute to the
      explanation of the important ethnic differences towards alcohol metabolism. Its
      assessment at the genomic DNA level with a procedure, excluding labelled probes,
      consisting of PCR (Polymerase chain reaction) amplification on dried blood spots
      and analysis of allele-specific RFLP (Restriction fragment length polymorphism)
      profiles, is well adapted to extensive studies in population samples. It can
      emphasize the importance of ADH as a genetic marker of population. Three ethnic
      groups (French Caucasians, Vietnamese Orientals, Black Africans from Niger) were
      studied. ADH2 and ADH3 genotypes were in equilibrium according to the Hardy
      Weinberg law. Important differences were noted in the distribution of ADH2 and
      ADH3 alleles.

PMID- 1361317
TI  - Sulphasalazine inhibition of human granulocyte activation by inhibition of second
      messenger compounds.
AB  - The effects of sulphasalazine on the production of second messenger compounds in
      human granulocytes have been characterised by various stimuli. The increases in
      cytosolic calcium, inositol trisphosphate, diacylglycerol, and phosphatidic acid
      (all important mediators of intracellular signal transduction) triggered by
      stimulation were inhibited by sulphasalazine. The metabolites 5-amino-salicylic
      acid and sulphapyridine were less potent inhibitors than the mother compound. It
      is concluded that sulphasalazine inhibits the synthesis of phosphoinositide
      derived second messenger compounds at the level of phospholipase C or its
      regulatory guanosine 5'-triphosphate (GTP) binding protein. Inhibition of
      phosphatidic acid synthesis was either due to the same mechanism, or to
      interaction with a phospholipase D regulating GTP binding protein.

PMID- 1361319
TI  - Sulphasalazine induced hepatitis in adult Still's disease.

PMID- 1361318
TI  - Complement factor 2 deficiency: a clinical and serological family study.
AB  - Inherited complement deficiencies are associated with a variety of connective
      tissue diseases. A family with inherited deficiency of complement factor 2 (C2)
      is described in which two family members with homozygous C2 deficiency developed
      cutaneous vasculitis and sicca syndrome. The other family members had
      heterozygous C2 deficiency and each member had the HLA-A25, B18, DR2 (w15)
      haplotype. The mother had seropositive rheumatoid arthritis. Further studies
      showed the presence of cryoglobulins, antibodies against endothelial cells, and
      anticardiolipin antibodies.

PMID- 1361321
TI  - 2nd Jenner International Glycoimmunology Meeting. United Kingdom, 1-2 November
      1992. Abstracts.

PMID- 1361320
TI  - Second Jenner international glycoimmunology meeting.

PMID- 1361322
TI  - Tricyclic azaergoline analogues: synthesis, structural modifications, and
      pharmacological studies.
AB  - As an extension of previous investigations on synthesis and dopamine autoreceptor
      activity of bicyclic ergoline analogues the tricyclic azaergoline analogues 9a
      and 9b were synthesized. Furthermore, the geometry of the aromatic beta
      ethylamine moiety of 9a,b was modified by stereoselective construction of the
      cycloheptenyl fused pyrazolopyridine derivative 7 and the aminomethyl substituted
      tricycle 10. Binding affinity of these compounds at dopamine (DA) receptor sites
      was investigated employing rat striatum homogenate: The compounds reveal modest
      to weak, but selective binding to a dopamine D-2 receptor when it is labelled
      with the DA-autoreceptor agonist [3H]-SND 919. In vivo studies with mice showed
      that 7, 9a,b, and 10 affect their CNS activity.

PMID- 1361323
TI  - Low density lipoprotein composition and oxidizability in coronary disease-
      apparent favourable effect of beta blockers.
AB  - The oxidative modification of LDL in vivo may have an important role in
      atherogenesis. To determine whether LDL fatty acid, anti-oxidant composition and
      sensitivity to oxidation in vitro is different in subjects with established
      atherosclerosis we compared 20 men with angiogram proven coronary disease with 25
      controls without clinical evidence of arterial disease. LDL-cholesterol, total
      triglycerides and LDL fatty acid composition did not differ significantly between
      the groups. LDL oxidation lag time and oxidation rate in coronary patients (132
      min, 0.02 absorbance units/min) and controls (140, 0.017) were not significantly
      different. However coronary disease subjects taking beta-blockers had evidence
      for reduced LDL oxidizability (lag time 148 +/- 7 min; oxidation rate 0.017 +/-
      0.002 abs units/min) compared with those not on beta-blockers (lag time 114 +/- 7
      min, rate 0.025 +/- 0.003, P < 0.005). LDL beta-carotene was significantly lower
      in coronary patients (0.92 mumol/mmol LDL cholesterol; controls 1.58; P = 0.001).
      LDL alpha-tocopherol appeared lower in coronary patients (2.8 mumol/mmol LDL
      cholesterol; controls 3.3; P = 0.056) and was significantly lower in smokers
      (2.56; non-smokers 3.24; P = 0.04). LDL oxidation rate was negatively correlated
      with LDL alpha-tocopherol (r = -0.51, P = 0.005).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1361324
TI  - Carvedilol, a new antihypertensive, prevents oxidation of human low density
      lipoprotein by macrophages and copper.
AB  - Growing evidence indicates that oxidized low-density lipoprotein (LDL) may
      promote atherogenesis. Therefore, inhibition of LDL oxidation may impede this
      process. Carvedilol is a vasodilating, beta-adrenoceptor blocking agent. As a new
      antihypertensive drug, carvedilol is unique by virtue of its potent antioxidant
      activity. Therefore, we tested the ability of carvedilol to inhibit the oxidation
      of LDL by either macrophages or Cu2+. Carvedilol inhibited LDL oxidation by
      macrophages in a dose-dependent manner, with an IC50 value of 3.8 microM, as
      assessed by a thiobarbituric acid reactive substance (TBARS) assay. Under the
      same conditions, propranolol showed only a mild inhibitory effect (IC50 > 100
      microM), while pindolol, atenolol and labetalol had almost no effect. Carvedilol,
      at 10 microM, almost completely inhibited the macrophage-induced increase in
      electrophoretic mobility of LDL, while other beta-blockers at 50-300 microM had
      no significant effect. Carvedilol inhibited superoxide release from mouse
      macrophages, which correlated well with its inhibition of LDL oxidation.
      Carvedilol also inhibited Cu(2+)-induced LDL oxidation with an IC50 value of 17
      microM, while all other beta-blockers were inactive up to 300 microM. These
      observations suggest that carvedilol might not only be an effective
      antihypertensive drug, but might also be effective in prevention of
      atherosclerosis.

PMID- 1361326
TI  - The pathobiology of HIV infection.
AB  - The follicular dendritic cells (FDCs) of the germinal center are known to absorb
      antigens in the form of immune complexes and to express them on the cell surface
      for long periods of time. Here, Cecil Fox and Michele Cottler-Fox propose that,
      as a result of FDC binding of immune-complexed viruses, lymphoid organs are the
      major reservoirs of HIV, and that FDCs play a key role in infection of CD4+ T
      cells.

PMID- 1361325
TI  - HLA polymorphisms and evolution.
AB  - Polymorphisms within the human MHC are of interest to immunologists, for their
      functional significance, and to geneticists, as markers of populations. Here,
      Eleanor Riley and Olle Olerup describe how molecular analysis of the HLA complex
      is beginning to reveal the true extent of class II diversity, and demonstrate the
      use of this information to clarify the historical relationships between different
      human populations.

PMID- 1361327
TI  - Malaria vaccine strategy.

PMID- 1361329
TI  - The Dentate Gyrus and its Role in Seizures. Symposium. Irvine, California,
      February 1991.

PMID- 1361328
TI  - Sulfhydryl modification of E. coli Cpn60 leads to loss of its ability to support
      refolding of rhodanese but not to form a binary complex.
AB  - Differential chemical modification of E. coli chaperonin 60 (cpn60) was achieved
      by using one of several sulfhydryl-directed reagents. For native cpn60, the three
      cysteines were accessible for reaction with N-ethylmaleimide (NEM), while only
      two of them are accessible to the larger reagent 4,4'-dipyridyl disulfide (4
      PDS). However, no sulfhydryl groups were modified when the even larger reagents
      5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) or 2-(4'-(iodoacetamido)anilino)
      naphthalene-6-sulfonic acid (IAANS), were employed, unless the chaperonin was
      unfolded. The cpn60 that had been covalently modified with NEM or IAANS, was not
      able to support the chaperonin-assisted refolding of the mitochondrial enzyme
      rhodanese, which also requires cpn10 and ATP hydrolysis. However, both modified
      forms of cpn60 were able to form binary complexes with rhodanese, as demonstrated
      by their ability to arrest the spontaneous refolding of the enzyme. That is,
      chemical modification with these sulfhydryl-directed reagents produced a species
      that was not prevented from interaction with partially folded rhodanese, but that
      was prevented from supporting a subsequent step(s) during the chaperonin-assisted
      refolding process.

PMID- 1361330
TI  - Hippocampal opioid peptides and seizures.
AB  - We have employed a molecular biological approach to study the dynamic status of
      hippocampal opioid peptides in response to seizures elicited by different
      experimental models, such as electroconvulsive shocks (ECS) and amygdaloid
      kindling. Both ECS- and kindling-induced seizures triggered an initial large
      release of enkephalin and dynorphin, but produced opposite long-term effects on
      the biosynthesis of these two peptides, an increase of enkephalin, and a drastic
      decrease of dynorphin. Electrical stimulation of the perforant pathway produced
      differential changes of enkephalin and dynorphin, which were identical to those
      of ECS and kindling. This finding confirmed our hypothesis that the perforant
      pathway was responsible for the mediation of ECS- and kindling-induced changes in
      opioid peptide turnover. Strongest evidence indicating a role for opioid peptides
      in mediating the expression of seizure-related behaviors was found using the
      kainic acid model, where we saw that hippocampal enkephalin was essential to the
      expression of kainic acid-induced wet dog shakes (a preconvulsive shaking
      behavior). Furthermore, it was found that the granular-mossy fiber pathway of the
      ventral, but not the dorsal, hippocampus was essential for the expression of this
      shaking behavior. However, destruction of the granular-mossy fiber pathway
      potentiated the seizures and hippocampal cell loss induced by kainic acid. This
      unexpected, yet extremely interesting, finding not only distinguished the roles
      of the granular-mossy fiber pathway in mediating wet dog shakes vs. convulsive
      seizures, but also challenged the dogma that this granular-mossy fiber pathway is
      essential for the expression of limbic seizures.

PMID- 1361331
TI  - Neurotransmitters and their receptors in human temporal lobe epilepsy.
AB  - Patients with medically intractable temporal lobe epilepsy (TLE) undergo medial
      temporal lobectomy with hippocampectomy for one of two reasons. (1) A lesion
      (tumor or arteriovenous malformation) adjacent to, but not invasive of, the
      hippocampus, results in the removal of the lesion and adjacent hippocampus in
      order to ensure a tumor-free margin. This group will be referred to as tumor
      related TLE (TTLE) patients. (2) The operation is performed when depth electrode
      recordings and other evaluative techniques point to the hippocampus as the focus
      of seizure initiation. This group will be referred to as cryptogenic TLE (CTLE)
      patients. Analysis of the hippocampi of these two groups of patients reveals that
      the TTLE hippocampus is quite similar to that of autopsy subjects in its chemical
      neuroanatomy. However, the dentate gyrus of the CTLE patients shows considerable
      morphological and cytochemical reorganization. This reorganization is
      characterized by a number of features. (1) There is a loss of granule cells which
      occurs either as a patchy loss and/or a thinning of the granule cell layer. (2)
      Remaining granule cells which contain dynorphin appear to produce recurrent
      collaterals into the inner molecular layer of the dentate gyrus. (3) In the
      subgranular region of the hilus (the polymorphic layer) there is a selective loss
      of interneurons immunoreactive for somatostatin, neuropeptide Y and substance P.
      (4) There appears to be an increase in fibers immunoreactive for somatostatin and
      neuropeptide Y which extend throughout the dentate molecular layer. Somatostatin
      fibers being less numerous than neuropeptide Y fibers (5). The distributions of a
      number of neurotransmitter receptors also show striking reorganization in the
      dentate gyrus of the CTLE hippocampus. (6) Second messenger systems protein
      kinase C and adenylate cyclase, and Na+, K(+)-ATPase activity, as determined by
      ouabain binding, is increased in the molecular layer of CTLE. This remodeling of
      the CTLE hippocampus may hold the key to the mechanisms of hyperexcitability of
      the granule cells in the hippocampus of this group, and consequently the
      generation of seizures. The removal of the hippocampus in CTLE patients results
      in good control of seizures, whereas removal of hippocampi that do not show such
      reorganization, in a group of patients classified as atypical CTLE patients,
      results in inadequate seizure control. These findings suggest a complex series of
      processes in converting the properly regulated granule cells into hyperexcitable
      ones.

PMID- 1361332
TI  - Synaptic connections of seizure-sensitive neurons in the dentate gyrus.
AB  - A selective loss of somatostatin- and neuropeptide Y-immunoreactive neurons has
      been reported in the dentate gyrus of rats with cerebral ischemia, following
      sustained electric stimulation, and in patients with non-tumor-related temporal
      lobe epilepsy. Three theoretical possibilities were tested that may explain why
      these neurons are more vulnerable than others, such as the cholecystokinin- and
      calcium-binding protein-containing cells: (1) the seizure-sensitive neurons are
      more involved in specific excitatory circuitry than are the seizure-resistant
      cells; (2) the somatostatin- and neuropeptide Y-immunoreactive neurons are less
      protected by inhibitory GABAergic inputs than cells immunoreactive for
      cholecystokinin; and (3) the seizure-sensitive neurons do not contain calcium
      binding proteins. The present results of light and electron microscopic, single
      and double, immunostaining experiments and co-localization studies performed on
      the hippocampal formations of rats and non-human primates, support the idea that
      the calcium-binding protein content of a neuron defines its seizure sensitivity.

PMID- 1361333
TI  - GABAergic septal and serotonergic median raphe afferents preferentially innervate
      inhibitory interneurons in the hippocampus and dentate gyrus.
AB  - Postsynaptic targets of the GABAergic septohippocampal and the serotonergic raphe
      hippocampal pathways were studied using anterograde tracing with Phaseolus
      vulgaris leucoagglutinin combined with pre- and postembedding immunocytochemistry
      in the rat. Two types of afferents were labeled in the hippocampus and dentate
      gyrus from the medial septum-diagonal band of Broca complex, one with large
      diameter varicosities and another with smaller terminals. The former type was
      shown to be immunoreactive for gamma-aminobutyric acid (GABA), and to innervate
      predominantly GABA-immunoreactive interneurons. Subsequently, these target
      interneurons were demonstrated to include all subpopulations of GABAergic cells
      which could be visualized by antisera against parvalbumin, calbindin D28k,
      calretinin, cholecystokinin, somatostatin, neuropeptide Y and vasoactive
      intestinal polypeptide. These types of interneurons have different afferent and
      efferent connections, and thus participate in different inhibitory processes in
      the hippocampal formation. The other subcortical pathway, the serotonergic
      projection from the median raphe nucleus, was also shown to establish synapses
      predominantly with GABAergic interneurons both in the hippocampus and in the
      dentate gyrus. In contrast to the septohippocampal projection, this pathway did
      not innervate all types of GABAergic neurons. They selected a particular
      subpopulation, i.e. those which contain calbindin D28k, and ignored those which
      contained parvalbumin or the other neurochemical markers. This suggests a strong
      functional specialization among local inhibitory circuits, as well as among the
      subcortical afferents originating in the septum and raphe. These findings suggest
      that a mechanism by which numerically small afferent pathways may have a profound
      global effect on the electrical activity of the hippocampal formation is the
      selective innervation of local interneurons. These GABAergic inhibitory cells, in
      turn, control the activity of large populations of principal cells. The level of
      GABAergic inhibition determines the degree of population synchrony and influences
      N-methyl-D-aspartate receptor-mediated epileptiform burst-firing. Thus, the
      specific subcortical modulation of hippocampal inhibitory circuits may also have
      fundamental implications for epileptogenesis.

PMID- 1361336
TI  - Biological Signalling Using Superoxide and Nitric Oxide Radicals. 98th conference
      of the Society of Biological Chemistry. Bavaria, Federal Republic of Germany,
      October 14-17, 1992. Abstracts.

PMID- 1361337
TI  - Analysis of Structure and Function of Proteins. 100th conference of the Society
      of Biological Chemistry. Rostock, 25 September 1992. Abstracts.

PMID- 1361335
TI  - Behavioural, biochemical and histological effects of AF64A following injection
      into the third ventricle of the mouse.
AB  - Behavioural, biochemical and histological effects were assessed following AF64A
      injected into the third ventricle of female NMRI mice. Doses from 3 to 7 nmol
      produced significant changes in behaviour, causing hyperactivity, reduced hole
      board exploration, rotational behaviour in a symmetrical Y-maze corresponding to
      a loss of alternation, abnormal behaviour in a plus-maze task of fear/anxiety
      with markedly increased exploration of the open arms and finally deficits in
      passive avoidance responding and spatial orientation in a Morris-type water maze.
      In this latter test, a cue learning deficit was noted for the two highest doses
      only. No histological changes of consequence were observed up to 5 nmol. Beyond
      this dose, at 6 and particularly 7 nmol, necrosis of parts of the hippocampus and
      septum was apparent. ChAT and AChE activity were decreased in the hippocampus but
      not in the cortex although the decreases were smaller than generally reported for
      AF64A-treated rats. ChAT and AChE reductions correlated highly with hyperactivity
      in the open-field and to a lesser extent, with spatial learning deficits.
      Monoaminergic activity was also affected in the hippocampus, but not in the
      cortex, at 4 nmol and above. NE and particularly 5-HT and 5-HIAA levels were
      reduced although the rate of 5-HT turnover was unaltered. A highly significant
      correlation was obtained between 5-HT effects and the increased open arm
      exploration in the plus-maze task of fear/anxiety. The behavioural effects and
      biochemical changes lasted at least 8-9 weeks postop.

PMID- 1361338
TI  - Purification and immunochemical studies of dipeptidyl peptidase IV from bovine
      kidney.
AB  - DPP IV from bovine kidney has been purified and characterized by molecular mass,
      pI, pH optimum and sensitivity to inhibitors. Polyclonal antibodies to the enzyme
      protein were used to show the location of dipeptidyl peptidase IV in microvillar
      membranes of bovine kidney using immunogold labelling by secondary antibody. The
      same antibodies reacted to DPP IV in Western blots of rat, pig and bovine kidney
      tissue, but failed to recognise the enzyme in bovine brain. This suggests that
      dipeptidyl peptidase IV may exist as different organ-specific rather than species
      specific proteins.

PMID- 1361334
TI  - Differentiation of rat dentate neurons by morphology and electrophysiology in
      hippocampal slices: granule cells, spiny hilar cells and aspiny 'fast-spiking'
      cells.
AB  - Intracellular recording and intracellular dye injection of single cells in the
      dentate region of rat hippocampal slices have been used to understand the
      different types of cells in the dentate and their possible functional
      organization. On the basis of combined electrophysiological and morphological
      data, the cells that have been sampled fall into three distinct groups: the
      granule cells, the spiny cells located in the hilus (the 'mossy' cell being the
      prototype), and the aspiny, 'fast-spiking' cells located throughout the region
      (many of which are likely to be GABAergic interneurons). Although there is some
      variability within each group, this variability is minor compared to the large
      differences between groups. To clarify these groups, each one is described first
      morphologically, at the level of the light microscope and histochemically, and
      then the three groups are described electrophysiologically, in terms of intrinsic
      electrophysiological characteristics, synaptic responses to perforant path
      stimulation, and possible roles in dentate circuitry. It is proposed that this
      apparent organization of neurons into three major classes be used as a starting
      point in our evolving understanding of the functional organization of the dentate
      region, and, in particular, the hilus. In addition, the possibility is raised
      that area CA3c cells of the hippocampus could be included in the dentate region
      as a fourth group. Together with the hilar cells, area CA3c could have the
      obviously important role of integrating the dentate circuitry with that of the
      hippocampus proper.

PMID- 1361339
TI  - The influence of lymphocyte counts and disease progression on circulating and
      inducible anti-HIV-1 cytotoxic T-cell activity in HIV-1-infected subjects.
AB  - OBJECTIVE: To evaluate specific anti-HIV cytotoxic T-lymphocyte (CTL) activity in
      relation to basic clinical and laboratory parameters used to follow HIV
      infection. METHODS: Lymphocytes from HIV-1-infected subjects with different
      clinical and immunologic features of HIV infection were tested for circulating
      and inducible anti-HIV CTL activity using autologous B-lymphoblastoid cells
      infected with recombinant vaccinia viruses expressing the HIV gag, pol and env
      genes as targets. Anti-HIV CTL were induced by stimulation with HIV-infected
      autologous lymphoblasts in vitro. RESULTS: We detected circulating anti-HIV CTL
      in asymptomatic subjects exclusively and found a significant association (P <
      0.01) between CD8+ lymphocyte counts > or = 900/microliters blood and detectable
      levels of circulating anti-HIV CTL. Subjects with circulating anti-HIV CTL also
      had a higher mean CD8+ lymphocyte count than those without detectable circulating
      activity (P < 0.001), but there was no significant difference in mean CD4+
      lymphocyte count. CD8+ human histocompatibility leukocyte antigen (HLA) class I
      restricted anti-HIV CTL were induced in all HIV-infected subjects tested
      following stimulation with HIV-infected autologous lymphoblasts in vitro. In
      subjects without detectable circulating anti-HIV CTL, circulating HLA-DR+ cells
      contributed to anti-HIV CTL activity induced by stimulation with HIV or
      concanavalin A in vitro. CONCLUSIONS: Circulating anti-HIV CTL activity is
      associated with CD8+ lymphocyte counts > or = 900/microliters. Anti-HIV CTL
      retain proliferative and functional capacity following in vitro stimulation with
      HIV and interleukin-2 through all stages of HIV infection. Persistent inducible
      anti-HIV CTL activity in subjects with advanced HIV disease and without
      circulating CTL suggests impaired activation and/or proliferation of the CTL in
      vivo.

PMID- 1361340
TI  - Detection of circulating p24 antigen-positive CD4+ cells during HIV infection by
      flow cytometry.
AB  - OBJECTIVES: To determine the amount of circulating CD4+ cells positive for
      intracellular p24 antigen during HIV infection, and to correlate the results with
      clinical, virological and therapeutic parameters. METHODS: Data were obtained
      from 24 anti-HIV-negative subjects (controls) and 47 anti-HIV-positive patients
      classified according to clinical diagnosis, serum p24-antigen assay results, and
      antiretroviral treatment with zidovudine, using a modified flow cytometric assay
      for the detection of intracellular HIV p24 antigen (p24-FCA) in circulating CD4+
      lymphocytes. RESULTS: The proportion of CD4+ lymphocytes positive for p24-FCA
      correlated well with HIV infection (1.685 +/- 1.902 versus 0.160 +/- 0.152 in
      controls; P < 0.001) and clinical progression [Centers for Disease Control (CDC)
      stage II: 1.310 +/- 1.187; CDC stage III 1.145 +/- 1.442; CDC stage IVA/C2: 2.335
      +/- 2.112; CDC stage IVC1: 2.066 +/- 2.420]. The percentage of CD4+ cells
      positive for HIV p24-FCA was inversely correlated with an absolute peripheral
      blood CD4+ lymphocyte count (Spearman's rank correlation = -0.324; P < 0.05).
      However, there was no statistically significant difference between patients in
      presence (n = 27; 1.938 +/- 2.095) or absence (n = 20; 1.343 +/- 1.594) of serum
      p24 Ag. The variable linked most strongly to the detection of intracellular p24
      in anti-HIV-positive patients was zidovudine treatment: the proportion of p24-FCA
      positive CD4+ lymphocytes was significantly lower (0.825 +/- 0.910) in the
      treated patients (n = 25) than in the untreated patients (n = 22; 2.662 +/-
      2.248; P < 0.001). CONCLUSIONS: Our results suggest that CD4+ p24 Ag-FCA is a
      rapid and easy test for the identification of the proportion of CD4+ lymphocytes
      with intracellular p24 Ag, and that it could be more appropriate than serum p24
      Ag assay in evaluating disease progression and efficacy of antiretroviral
      treatment.

PMID- 1361341
TI  - Report and recommendations for the first national conference on teaching of
      transcultural nursing.

PMID- 1361342
TI  - Determination of extracellular glutamate after local K+ stimulation in the
      striatum of non-anaesthetised rats after treatment with dopaminergic drugs-
      studies using microdialysis.
AB  - The present experiments were performed in order to investigate the effects of
      dopamine(DA)ergic drugs on the concentrations of extracellular glutamate (GLU) in
      the striatum of non-anaesthetised, freely moving rats by using microdialysis and
      to get further information about the interactions between glutamatergic and
      dopaminergic pathways. GLU was determined after pre-column derivatisation with o
      phthaldialdehyde by HPLC and fluorescence detection. For increasing the fraction
      of extracellular GLU which is of neuronal origin, an enhanced release of this
      neurotransmitter was evoked by 100 mM K+ administered via the dialysis probe.
      This stimulation was applied twice in each experiment, at the second time after
      administration of a subcutaneously (s.c.) given DAergic drug. For basal
      conditions, a perfusion fluid containing 148.2 mM Na+, 4mM K+, 1.2 mM Ca2+ was
      used, for conditions of stimulation with 100 mM K+ the Na+ concentration was
      reduced correspondingly. Activation of the D1 receptor with the selective D1
      sector agonist SKF 38393 ((+/-) 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8
      diol) 15 mg/kg) failed to influence the stimulated release of GLU, and neither a
      combination of the selective D2 antagonist (-)sulpiride (150 mg/kg) with the
      mixed D1/D2 agonist apomorphine (1 mg/kg), nor a combination of sulpiride (150
      mg/kg) with SKF 38393 (15 mg/kg) were effective. Also the two selective D2
      agonists quinpirole (0.5 mg/kg) or talipexole (50 micrograms/kg) had no
      significant influence on the release of GLU. The results suggest that DA receptor
      agonists have less effect on the K(+)-stimulated GLU-release than might be
      expected from in vitro studies or behavioral experiments (Kornhuber and
      Kornhuber, 1986).

PMID- 1361343
TI  - Dopaminergic neurotransmission in somatodendritic and terminal areas of the rat
      brain: susceptibility to modulation by D1 and D2 receptors and to axotomy.
AB  - We have investigated the influence of D1 and D2 dopamine receptor active drugs on
      dopamine (DA) release in substantia nigra (SN), striatum and limbic forebrain in
      intact and in hemisected rats in vivo. DA release was indirectly assessed as 3
      methoxytyramine (3-MT) accumulation following monoamine oxidase inhibition by
      pargyline. Hemisection per se had no effect on the 3-MT accumulation in the SN.
      Neither, had SCH 23390, SK & F 28393, or cis-flupentixol any effect in the SN in
      intact animals or in the lesioned side in hemisected animals. SCH 23390 slightly
      increased the 3-MT accumulation both in the striatum and limbic forebrain,
      indicating a stimulatory action on DA release, but SK & F 38393 had no effect in
      these brain regions. A difference between the striatum and the limbic forebrain
      was that the effects of SCH 23390, and cis-FPX were almost abolished following
      hemisection in the limbic forebrain, but only partially reduced in the striatum.
      In summary, our data give further support for the concept that neither D1 nor D2
      dopamine receptors have any pronounced influence on the DA release in the SN. The
      data also indicate operational differences in the feedback regulation of limbic
      versus striatal dopaminergic transmission.

PMID- 1361344
TI  - New Pathways of Phagocyte Activation. 4th Phagocyte Discussion Meeting.
      Edinburgh, United Kingdom, May 1992.

PMID- 1361346
TI  - [RFLPs study of parental origin and mechanism of 3 cases with X chromosome
      structural abnormality].
AB  - In this study, we analysed the parental origin and mechanism of X chromosome
      abnormalities in 3 cases by using RFLPs on short or long arm of X chromosome as
      genetic markers. Their karyotypes were 46,X,dup(X)(p21); 46,X,del(X)(p11);
      46,X,i(Xq). The results demonstrated that the dup(X)(p21) and the del(X)(p11)
      were of paternal origin and i(Xq) was of maternal origin. The dup(X)(p21) arose
      from an unequal sister chromatid exchange. The del(X) (p11) occurred through X
      chromosome breakage and deletion mechanism. The i(Xq) resulted from X chromosome
      centromere misdivision in oocyte.

PMID- 1361347
TI  - School refusal.

PMID- 1361348
TI  - International Conference on Advances in AIDS Vaccine Development. 4th Annual
      Meeting of the National Cooperative Vaccine Development Group for AIDS. Marco
      Island, Florida, October 15-19, 1991.

PMID- 1361345
TI  - Phagocyte activation in coronary artery disease.
AB  - Recent studies suggest that granulocytes (PMNs) play a role in the pathogenesis
      of acute and chronic myocardial ischemia and extension of myocardial injury.
      Granulocytes can release a variety of molecules mediating tissue injury which act
      synergistically with other molecules and cells. The aim of our investigation was
      to evaluate the granulocyte function in patients affected by coronary artery
      disease (CAD) and during coronary angioplasty (PTCA). We studied 20 patients
      suffering from CAD. The PMN's aggregating activity was greater in the coronary
      sinus than in the aorta (P < 0.01). The increase in aggregating activity was
      evident in patients who were smokers: their cells release significantly lower
      quantities of leukotriene C4 (P < 0.025). In the 20 patients who underwent
      coronary angioplasty we analyzed superoxide release after stimulation with
      phorbol-myristate-acetate (PMA). The results showed a greater decrease of PMN's
      superoxide production in the coronary sinus than in the aorta (P < 0.05). In all
      patients affected by CAD we evaluated the PMN's expression of CD11b/CD18 membrane
      integrins. In these patients the increase in expression of CD11b/CD18 was
      statistically significant in comparison with the controls (P < 0.01). This
      increase in expression correlates with a higher aggregation (r = 0.87, P <
      0.001). The potential role of leukocytes, oxygen radicals, leukotrienes and
      granulocyte enzymes in the pathophysiology of myocardial injury due to regional
      ischemia and reperfusion is an area of intense investigation. This paper presents
      studies carried out in vivo which have been instrumental in demonstrating the
      role of granulocytes as mediators of myocardial ischemia.

PMID- 1361349
TI  - Immunotherapy of HIV-seropositive patients: preliminary report on a dose-ranging
      study.

PMID- 1361350
TI  - Vaccine therapy using rgp 160 in early HIV infection.

PMID- 1361351
TI  - HLA phenotype is a factor in determining rate of disease progression and outcome
      in HIV-1-infected individuals.
AB  - HLA allele frequencies were examined for possible association(s) with the rate of
      disease progression and with the disease outcome (AIDS diagnosis) in a population
      of HIV-1-infected individuals. Certain alleles were associated with the relative
      rate of CD4+ T-cell decline. Association of particular alleles with several
      disease outcomes associated with infection was also observed. It is important to
      keep these two aspects (disease progression, AIDS diagnosis) separate when
      studying HLA in the HIV-1-infected population. Alleles that may play a role in
      the rate of virus speed by effecting the immune response may be different from
      those found to be associated with a particular disease. We feel that the only
      truly informative data, in this regard, can be generated from a relative precise
      determination of the time of infection (to study disease progression) and
      adequate numbers of individuals with specific diseases to study specific disease
      association. If such data can be generated we will have a much better
      understanding of the pathogenetic process(es) of HIV-1 infection.

PMID- 1361353
TI  - Comparison of the mouse antibody response to different antigenic formulations
      incorporating a synthetic peptide representing the heavy chain second
      complementarity-determining region of a mouse monoclonal anti-CD4 antibody.

PMID- 1361354
TI  - Summary: Clinical Immunology Working Group.

PMID- 1361352
TI  - Clonal analysis of T-cell responses to the HIV-1 envelope proteins in AIDS
      vaccine recipients.
AB  - Both CD4+ and CD8+ CTL responses specific for the HIV-1 envelope proteins can be
      elicited in seronegative humans by candidate AIDS vaccines. The phenotype of the
      responding CTL depends upon the nature of the vaccine, with CD8+ CTL being found
      exclusively in recipients of live virus vaccines. Both types of CTL are active
      against HIV-1-infected cells in vitro. However, the potential efficacy of vaccine
      induced CTL in preventing infection in vaccinated individuals exposed to HIV-1 is
      unknown and is likely to be dependent upon complex factors including lytic
      activity against divergent strains, cytokines produced, and the lysis of
      noninfected CD4+ T cells.

PMID- 1361355
TI  - Modification of the circadian rhythm of onset of acute myocardial infarction by
      long-term antianginal treatment.
AB  - OBJECTIVE: To elucidate the mechanism of the circadian pattern of onset of acute
      myocardial infarction by examining the effects of prior antianginal treatment
      upon it. DESIGN: Retrospective analysis of clock time of the onset of acute
      myocardial infarction by linear modelling to define the circadian distribution of
      hourly onset rates and to examine the deviation of treated groups of patients
      from this distribution. SETTING: Coronary care unit in a general hospital taking
      unselected acute admissions from a district of 0.9 million people. PATIENTS: A
      series of 2231 patients with confirmed acute myocardial infarction. RESULTS: A
      major 24 h cycle and smaller 12 h and 6 h cycles were present in patients not
      taking antianginal medication. Onset rates varied twofold over the day, with
      maxima around 10.00 am and 10.00 pm. This pattern was unchanged in patients on
      prior treatment with regular nitrates, but in those who had been taking a beta
      blocker or a calcium antagonist the 24 h cycle was absent. CONCLUSIONS: These
      results are best explained by the shared property of beta blockers and calcium
      antagonists to reduce blood pressure and myocardial oxygen demand. The mid
      morning peak of the onset of myocardial infarction is attributable to the
      physiological increase in sympathetic drive and cardiac work at that time. The
      data are not consistent with the triggering of the 24 h periodicity by
      fluctuations in coronary tone or haemostatic activity.

PMID- 1361356
TI  - Onset and recovery of rocuronium (Org 9426) and vecuronium under enflurane
      anaesthesia.
AB  - We have studied the onset, duration of action and recovery index of twice the
      ED90 of rocuronium (Org 9426) (0.6 mg kg-1) and of vecuronium (0.08 mg kg-1) in
      patients during enflurane anaesthesia. Rocuronium had a significantly shorter
      mean onset time of 1.8 (SD 0.4) min, compared with vecuronium 3.4 (0.8) min.
      Clinical duration (time for the first twitch in the train-of-four to recover to
      25% of control) was similar for both drugs (29 (10) min vs 31 (12) min).
      Spontaneous recovery times (TOF ratio 70%) did not differ significantly between
      rocuronium (47 (10) min) and vecuronium (44 (11) min).

PMID- 1361357
TI  - Effect of fentanyl on ventilatory resistances during barbiturate general
      anaesthesia.
AB  - Fentanyl has been shown to increase the overall resistance to inspiratory flow of
      the ventilatory system (Rmax). Rmax is the sum of the airway resistance (Raw) and
      of the non-Newtonian resistance (delta R) which may result from the viscoelastic
      properties of the thoracic tissues, from inequalities of the regional time
      constants within the lung, or from both. A bronchoconstrictor challenge may
      increase the magnitude of variation in regional time constants. Thus, in order to
      describe the effect of fentanyl on the two components of Rmax, this study was
      performed, with the end-inflation occlusion method, during paralysis and
      mechanical ventilation in 10 normal men undergoing barbiturate anaesthesia for
      minor urological procedures. The patients were anaesthetized with methohexitone
      and paralysed with vecuronium. Before administration of fentanyl, delta R
      accounted for 56% of Rmax. Fentanyl 5 micrograms kg-1 elicited a significant
      increase in Rmax (+34.5%; P = 0.005) and a parallel increase in both Raw (+35.2%,
      P = 0.017) and delta R (+33.5%, P = 0.005). The increase in Raw, but not in delta
      R, was reversed by atropine, suggesting that the increase in these two components
      of Rmax was not linked. Thus fentanyl increased both components of Rmax, but the
      effects of fentanyl on Raw and delta R seemed to depend on different mechanisms.

PMID- 1361358
TI  - New anticancer agents: taxol, camptothecin analogs, and anthrapyrazoles.
AB  - Taxol, an agent with a unique mechanism of action, has been shown to be highly
      active in patients with refractory ovarian cancer and may well have significant
      activity in other malignancies such as breast and lung cancer. The camptothecin
      analogs, another unique class of agents, have demonstrated antitumor activity in
      phase I and II trials. Finally, the anthrapyrazoles are intercalating agents with
      clinical activity in breast cancer and a toxicity profile that may permit
      increased dose intensity using colony-stimulating factor support. While this
      review focuses on these three drug classes, a number of other agents with
      apparently unique mechanisms of antitumor activity and unusual dose-limiting
      toxicities are in earlier development. These include antimetabolites; inhibitors
      of DNA, RNA, or protein synthesis; differentiating agents; agents that inhibit
      tumor growth by binding to growth factors; and agents whose mechanism of action
      is best classified as unknown.

PMID- 1361359
TI  - [Bronchial asthma--care and therapy of status asthmaticus in the intensive care
      unit].

PMID- 1361360
TI  - The calculation of molecular similarity: alternative formulas, data manipulation
      and graphical display.
AB  - The use of electrostatic potential comparisons between molecules for the
      elucidation of structure activity relationships is now a well-established
      modeling technique. The Carbo and Hodgkin similarity indices are used extensively
      to make quantitative comparisons of this nature; yet their roots are found in the
      overlap of electron density distribution, with both formulas utilizing a product
      based numerator. Two new similarity indices are suggested that calculate the
      electrostatic potential similarity using a difference-based numerator. The form
      of the new indices allows the creation of additional software functions that
      enhance the flexibility of similarity calculations and permit the creation of
      similarity maps. The general properties of these software functions and all
      indices are discussed and applied to a series of dopamine D2 receptor agonists.

PMID- 1361361
TI  - Origin of the ammonia used for mitochondrial citrulline synthesis as revealed by
      13C-15N spin coupling patterns observed by 13C NMR.
AB  - The sources of ammonia used by isolated, intact rat liver mitochondria in the
      production of citrulline have been investigated in situ using a novel methodology
      based on the analysis of 13C-15N heteronuclear couplings observed by 13C NMR.
      Isolated mitochondria from rat liver were incubated with ornithine, 13CO3H- and
      15NH4Cl, using unlabeled glutamate or glutamine as alternative,
      intramitochondrial nitrogen donors. The production of (7-13C, 8-15N) or (7-13C, 8
      14N) citrulline was determined in situ by 13C NMR and the relative proportions of
      15N- and 14N-citrullines confirmed by high resolution 13C NMR analysis of the C-7
      citrulline resonance observed in perchloric acid extracts prepared at the end of
      the incubations. The 15N fractional enrichment of the intramitochondrial NH3 pool
      was manipulated either by modifying the 15N enrichment of added 15NH4Cl, or by
      altering the concentration of the unlabeled nitrogen donors in the incubation
      medium. Fractional 15N enrichments measured in the N-8 nitrogen of the resulting
      (7-13C) citrulline closely paralleled those of the external 15NH4Cl with minor
      dilutions derived from the unlabeled nitrogen contribution from the alternative
      substrates. In the presence of 10 mM 15NH4Cl, 10 mM glutamate contributed 4% of
      the citrulline N-8 nitrogen. Under similar conditions, the contribution of
      nitrogen from 10 mM glutamine to N-8 citrulline was 6%. These results indicate
      that the primary source of ammonia used for citrulline synthesis by isolated,
      intact rat liver mitochondria is extramitochondrial, providing also an
      illustration of the use of 13C-15N spin coupling patterns observed by 13C NMR, as
      a new tool in the study of ammonia metabolism.

PMID- 1361362
TI  - [The role of carnosine in the function of soluble of guanylate cyclase].
AB  - The effect of carnosine on activation of human platelet soluble guanylate cyclase
      has been studied in 105,000 g supernatants and partially purified haem-deficient
      enzyme preparations. In the 105,000 g supernatant carnosine (1 mM) inhibited (by
      about 70%) the enzyme activation caused by sodium nitroprusside. In partially
      purified haem-deficient guanylate cyclase preparations the inhibition of enzyme
      activation by sodium nitroprusside was 86%; further addition of carnosine had no
      effect on the enzyme activity. The strength of the activating effect of
      protoporphyrin IX on partially purified haem-deficient guanylate cyclase did not
      differ from that for the 105,000 g supernatant; this stimulating effect did not
      change after carnosine addition. A conclusion is drawn that the inhibiting effect
      of carnosine on the ability of guanylate cyclase to be activated by sodium
      nitroprusside is due to the dipeptide interaction with the guanylate cyclase
      haem.

PMID- 1361363
TI  - Ontogeny of gastric function in the pig: acid secretion and the synthesis and
      secretion of gastrin.
AB  - Gastric acid secretion, gastrin-releasing peptide (GRP)-stimulated gastrin
      secretion and concentrations of somatostatin in gastric tissues were studied in
      sucking pigs (n = 48). In addition, gastrin concentrations in plasma and antral
      tissue were measured in fetal and sucking pigs (n = 66) from 22 days before birth
      (93 days gestation) to 36 days of age. From 3 days of age littermate pairs were
      treated twice a day with either saline (n = 20) or adrenocorticotropin [ACTH (1
      24); n = 20]. Pentagastrin-stimulated acid secretion per unit stomach weight was
      39 +/- 7 mumol H+/g/h at 0-1 day, increased to 194 +/- 15 mumol H+/g/h at 5-7
      days and plateaued. Antral gastrin concentration was 0.14 nmol/g 10 days before
      birth and increased to 2.7 nmol/g at 5 weeks of age. Plasma gastrin was 25 +/- 2
      pmol/l at 22 days before birth, increased to 102 +/- 14 pmol/l at birth and
      decreased during the postnatal period. Somatostatin concentrations were higher in
      antral than fundic tissues (p < 0.05) and remained constant during the postnatal
      period. Increased levels of glucocorticoids in plasma following ACTH treatment
      had no effect on the studied parameters except that it reduced basal (p < 0.07)
      and GRP-stimulated (p < 0.05) plasma gastrin concentrations at 6-7 days of age.
      Development of acid secretion and its gastric regulatory peptides in the pig is
      different from that in the rat in that it occurs at an earlier age and does not
      appear to be greatly influenced by elevated glucocorticoid levels from 3 days
      after birth.

PMID- 1361364
TI  - Topographical changes in alpha power in medicated and unmedicated schizophrenics
      during digits span reverse matching test.
AB  - The topographical distribution of alpha power reduction was compared in nine
      unmedicated schizophrenics (predominantly never-treated), 17 medicated
      schizophrenics, and 15 normal controls. The task involved four procedures: (1)
      listening to signal sound, (2) listening to digits for memorization, (3) after
      listening, and (4) listening to digits for recognition. The electroencephalograms
      (EEGs) during each procedure were analyzed with Fast Fourier Transformation and
      compared with EEGs at rest. While listening to the digits, medicated
      schizophrenics showed less alpha power reduction than normal controls and
      unmedicated schizophrenics. In addition, there were correlations found between
      the degree of alpha power reduction and medication dose, and score of chronic
      symptoms. These suggest that patients with different clinical backgrounds have
      differing cerebral activity.

PMID- 1361365
TI  - SPEM impairment in drug-naive schizophrenic patients: evidence for a trait
      marker.
AB  - Smooth-pursuit eye movements (SPEM) were assessed in healthy subjects and in drug
      naive, chronic, and residual schizophrenic patients. SPEM gain was found to be
      decreased in all the schizophrenic patients who also exhibited a significant
      increase in the rate of saccades. The frequency of square-wave jerks was the same
      in schizophrenic patients and normal controls, suggesting that the primary
      abnormality in schizophrenic patients was a low gain rather than a defect of the
      saccadic system. Patients were retested 1 month later, and stability of gain was
      high even in formerly drug-naive subjects who had been treated for 1 month with
      neuroleptic drugs. Altogether these results confirm the conclusions of most
      previous studies, extend them to drug-naive schizophrenic patients, and favor the
      hypothesis that SPEM impairment is a trait marker in schizophrenia.

PMID- 1361367
TI  - Cardiorespiratory measures and their role in studies of performance. Workshop.
      Dayton, Ohio.

PMID- 1361366
TI  - MDMA ("ecstasy") and panic disorder: induction by a single dose.

PMID- 1361368
TI  - Autoimmune gastritis: tolerance and autoimmunity to the gastric H+/K+ ATPase
      (proton pump).
AB  - The alpha and beta subunits of the gastric H+/K(+)-ATPase (proton pump) have been
      identified as the major molecular targets of parietal cell autoantibodies
      associated with pernicious anaemia and with murine experimental autoimmune
      gastritis (EAG) induced by neonatal thymectomy. Recent studies with EAG suggest
      that the mechanisms of peripheral tolerance and autoimmunity to extrathymic
      autoantigens are mediated by subsets of "regulator" and "effector" CD4+ T cells,
      respectively. The persistence of "effector" CD4+ autoreactive T cells in the
      periphery may be a direct consequence of the delayed developmental expression of
      the target autoantigen. We hypothesize that cytokines produced by the "regulator"
      T cells prevent the clonal expansion of the "effector" autoreactive T cells, and
      that neonatal thymectomy induces organ-specific autoimmunity in genetically
      susceptible individuals by the reduction of the "regulator" T cell population.

PMID- 1361369
TI  - Inhibition of phosphatidylserine synthesis induced by a CD4 mAb, B66.6 in Jurkat
      T cells.
AB  - A monoclonal antibody, B66.6, previously classified in the cluster of
      differentiation 4 (CD4), has been studied and compared with another CD4
      monoclonal antibody, IOT4. It was found that B66.6 but not IOT4 was able to
      mobilize Ca2+ from intracellular stores in the Jurkat T cell line. Ca2+
      mobilization was followed by a decrease in the extent of phosphatidylserine
      synthesis. In the presence of the phorbol ester, phorbol 12,13-dibutyrate, B66.6
      induced interleukin-2 synthesis. Altogether, the results indicate that the CD4
      monoclonal antibody, B66.6, mimics other T cell activators such as CD3 and
      confirm that the inhibition of phosphatidylserine synthesis in activated T cells
      follows the mobilization of Ca2+ from intracellular stores and is independent of
      the activation of the Ca(2+)-and phospholipid-dependent protein kinase C.

PMID- 1361370
TI  - Transcription factors, translocations, and leukemia.
AB  - The frequent occurrence of TF gene involvement in translocations associated with
      leukemia is remarkable, although not yet explained. The wide variety of TFs
      involved in these translocations and the different stages of cellular maturation
      argue against a unifying mechanism. Recombinases, active during B-cell and T-cell
      development, have been implicated in gene arrangements involving TCR genes and in
      the SIL/SCL rearrangement, which involves two genes not normally rearranged.
      However, other mechanisms must clearly be active in generating these molecular
      abnormalities and perhaps they relate to the multistep maturation and
      differentiation processes and continuous cell turnover seen in hematopoietic
      cells. The difficulties in obtaining human solid tumor samples may make it more
      difficult to identify translocations involving TF genes in solid tumors.
      Recently, the cytogenetic analysis of solid tumors has improved and specific
      cytogenetic abnormalities have been associated with specific types of tumors.
      With advanced techniques, such as fluorescent in situ hybridization (a technique
      that does not depend on cell growth) and PCR, abnormalities involving TF genes
      will be discovered. Abnormalities of TF genes, other than translocations, have
      been seen in a broad variety of nonhematopoietic malignancies. The p53 protein
      has been shown to bind DNA in a sequence-specific fashion and interact with a
      variety of DNA tumor virus oncoproteins. The broad range of cell types that
      harbor p53 abnormalities suggests that TF abnormalities will likely be implicated
      in many solid tumors. We have detailed several examples of how gene
      rearrangements that accompany chromosomal translocations in acute leukemia can
      alter the expression or activity of cellular TFs. Several translocations generate
      fusion RNA transcripts and fusion TF proteins with altered functional
      characteristics. Other translocations result in the expression of a gene not
      normally detectable in hematopoietic cells or alter the level of its expression,
      or affect the promoter usage or exon structure of the gene (Table 2). Studies are
      underway in many laboratories to characterize the biologic activity of these
      abnormal TFs and it remains to be proven that these molecular abnormalities are
      directly linked with leukemogenesis. The identification of abnormal fusion
      transcripts and proteins may allow specific therapies to be directed against
      "tumor-specific" DNA, mRNA, or protein targets. Therapeutic strategies based on
      antisense or ribozyme technology may be used to turn off expression of these
      genes and inhibit leukemia cell growth. Immunologic methods can also be used to
      direct therapy against the malignant cells.

PMID- 1361371
TI  - Dyskeratosis congenita fibroblasts are abnormal and have unbalanced chromosomal
      rearrangements.
AB  - Dyskeratosis congenita (DC) is a rare inherited disorder characterized by bone
      marrow failure, dystrophic changes in the skin and mucous membranes, and a
      predisposition to malignancy. The DC locus has been mapped to Xq28. The primary
      defect responsible for this disease remains unknown. We have studied four
      patients with this disease, three from one family and one from another. In all
      four patients, primary skin fibroblast cultures were abnormal both in morphology
      (polygonal cell shape, ballooning, and dendritic-like projections) and in growth
      rate (doubling time about twice normal). Fibroblast survival studies using four
      clastogens (bleomycin, diepoxybutane, mitomycin-c, and 4-nitroquinoline-1-oxide)
      and gamma radiation showed no significant difference between DC and normal
      fibroblasts. Cytogenetic studies performed on peripheral blood lymphocytes showed
      no difference between DC and normal lymphocytes with or without prior incubation
      with clastogens. However, bone marrow metaphases from one of three patients and
      fibroblasts from two of four patients (who were the eldest of the 4) showed
      numerous unbalanced chromosomal rearrangements (dicentrics, tricentrics, and
      translocations) in the absence of any clastogenic agents. Cell-specific
      differences and a higher rate of chromosomal rearrangements in the older patients
      appear to correlate with the clinical evolution of the disease. These findings
      suggest that the DC defect predisposes DC cells to developing chromosomal
      rearrangements.

PMID- 1361373
TI  - Measures of tumor proliferative activity.
AB  - Tumor proliferative activity, or labeling index, is of interest for gaining
      insight into the biologic properties of human neoplasm and for providing clinical
      information that might guide patient management. There has been an abundance of
      literature reporting experience with standard and newer techniques of measuring
      tumor proliferative activity. These methods are reviewed with emphasis on
      technical issues. Particular attention is paid to the development and use of
      monoclonal antibodies, Ki-67 and anti-PCNA/cyclin. These antibodies are readily
      available and relatively simple to use. The former has recently been shown to be
      of prognostic value in non-Hodgkin's large cell lymphomas. A number of studies
      suggest that indices using these techniques could be useful for a variety of
      carcinomas, soft tissue tumors, and tumors of the central nervous system.

PMID- 1361372
TI  - Structural and functional analysis of oncogenes and tumor suppressor genes in
      adult T-cell leukemia/lymphoma shows frequent p53 mutations.
AB  - The human T-cell lymphotropic virus type I (HTLV-I) is capable of inducing adult
      T-cell leukemia/lymphoma (ATLL). However, the long latency period between
      infection and development of ATLL, as well as the small fraction of the infected
      population that actually develops this disease, suggest that additional factors
      are involved in its pathogenesis. Therefore, we performed a molecular analysis of
      10 cases of ATLL presenting in a nonendemic area that were shown to have HTLV-I
      sequences by polymerase chain reaction as well as clonal T-cell receptor beta
      gene rearrangements. We analyzed these cases for alterations in some of the
      oncogenes and tumor suppressor genes frequently involved in hematopoietic
      neoplasia. Specifically, we used a single-strand conformation polymorphism assay
      to determine the presence of mutations in the p53 tumor suppressor gene, as well
      as the K-RAS, N-RAS, H-RAS, and c-myc oncogenes. In addition, we studied the c
      myc gene for rearrangements by Southern blotting and assessed expression of the
      retinoblastoma (Rb) and p53 genes by immunostaining. Analysis of the c-myc gene
      and the RAS family of oncogenes did not show any alterations. Also, the Rb gene
      was expressed in all cases analyzed. However, we found mutations of the p53 gene
      in 3 of the 10 cases and these results were confirmed by sequence analysis. In
      two of these cases, we showed by restriction fragment length polymorphism
      analysis of chromosome 17p sequences that the p53 mutations were accompanied by a
      loss of heterozygocity. Also, these mutations correlated with an altered pattern
      of p53 expression. Thus, mutations in the p53 locus may be a cofactor for the
      development of ATLL in some cases, whereas the c-myc, Rb, and RAS genes do not
      appear to be involved in these neoplasms.

PMID- 1361374
TI  - Id expression during mouse development: a role in morphogenesis.
AB  - We have characterized the spatial and temporal pattern of Id transcription during
      mouse embryogenesis. The Id gene encodes a helix-loop-helix (HLH) protein which
      can heterodimerize with the ubiquitously expressed HLH protein products of the
      E2A gene, and prevent them from binding DNA either alone or as a heterodimer with
      tissue specific HLH transcription factors such as the muscle determination gene,
      MyoD1 (Benezra et al., 1990: Cell 61:49-59). Since Id has been shown to be down
      regulated during induced differentiation in several cell lines, it has been
      postulated that Id plays a general inhibitory role in cell differentiation
      (Benezra et al., 1990). In situ analysis of Id mRNA expression in the mouse
      embryo was performed in order to determine whether the pattern of Id expression
      is consistent with this postulate. A detailed study throughout the entirety of
      mouse postimplantation development reveals that Id is expressed upon gastrulation
      at very high levels in almost all regions of the mouse embryo and expression
      declines as embryogenesis proceeds. In skeletal muscle, in which the inhibitory
      action of Id has been established in tissue culture models (Benezra et al.,
      1990), Id and the HLH myogenic factors are expressed in a mutually exclusive
      manner suggesting that myogenic precursors do not express both types of HLH gene
      products. In addition, Id colocalizes both spatially and temporally with Hox-7.1,
      a murine homeobox gene which is associated with regions of high cell
      proliferation and positional fate assignment.

PMID- 1361375
TI  - Neural transplantation: problems and prospects for therapeutic application.
AB  - Successful demonstrations of behavioural recovery in a variety of lesion and
      mutant animal models have encouraged the application of neural transplantation to
      the alleviation of neurodegenerative disease. Apart from the continuing shortage
      of foetal tissue, the major problems to be resolved for successful application of
      neural transplantation to humans are: first, immune rejection of allograft tissue
      and its pathological consequences to both graft and host tissue; and second, the
      establishment of normal and extensive graft-host connectivity. Recent
      developments in transplant research are beginning successfully to apply a number
      of strategies to resolve these problems.

PMID- 1361376
TI  - Dynamic neuropathology.

PMID- 1361377
TI  - [Cancer of the lung: focus in 1992. Report of the "6th World Conference on Lung
      Cancer", Melbourne, November 10-14, 1991 (the Lyons Group for Thoracic
      Oncology)].

PMID- 1361379
TI  - Urinary glycylprolyl dipeptidyl aminopeptidase (GP-DAP) in insulin-dependent
      diabetic patients.
AB  - Urinary glycylprolyl dipeptidyl aminopeptidase (GP-DAP) concentrations were
      determined in 36 insulin-dependent diabetic children aged 4-18 years with a
      duration of diabetes ranging from 1 month to 14 years. Abnormal urinary GP-DAP
      concentrations were found in 19 of the 36 patients. Twelve of 27 patients without
      microalbuminuria also had increased urinary concentrations of GP-DAP. There was a
      significant correlation between urinary GP-DAP and plasma fructosamine (r = 0.52,
      p < 0.001). Our data suggest that urinary GP-DAP may be used as a marker for
      diabetic nephropathy. However, there is also a possibility that increased urinary
      GP-DAP concentrations are functionally related to poor metabolic control.
      Longitudinal studies are needed to establish the clinical usefulness of urinary
      GP-DAP.

PMID- 1361378
TI  - Proliferative responses of CD4+ T-cell population to ovalbumin in patients with
      atopic dermatitis who are sensitive to hen eggs.
AB  - Proliferative responses of peripheral blood mononuclear cells and T cells with
      monocytes to ovalbumin were significantly higher than those of B cells with
      monocytes to ovalbumin in patients with atopic dermatitis (AD) who were sensitive
      to hen eggs. The CD4+ T-cell/CD8+ T-cell ratios (the values obtained by dividing
      the maximum stimulation index of CD4+ T cells with monocytes to ovalbumin by the
      maximum stimulation index of CD8+ T cells with monocytes to ovalbumin) were
      significantly higher in AD patients sensitive to hen eggs than in non-atopic
      healthy controls. The proliferative responses of CD4+ T cells with monocytes to
      ovalbumin were more intensive than those of CD8+ T cells with monocytes in
      patients with AD sensitive to hen eggs compared with non-atopic healthy controls.
      These results suggest that the cells responding to ovalbumin are predominantly
      CD4+ T cells. However, there was no relationship between the stimulation index of
      proliferative responses of peripheral blood mononuclear cells to ovalbumin and
      RAST scores for hen eggs. Thus it is possible that the majority of the CD4+ T
      cells which respond to ovalbumin are not CD4+ helper T cells for IgE production.

PMID- 1361380
TI  - [The timely diagnosis of postoperative clostridial infection].
AB  - Authors report a case of clostridial myonecrosis postcholecystectomy. The causes
      of the occurrence of this severe, frequently lethal complication are reviewed, as
      well as the difficulties of an early diagnosis, the only factor able to save the
      patient. The curative treatment of the detected infection requires the initiation
      of a series of local and general measures and a permanent cooperation between the
      surgeon, the specialist in resuscitation and the infectionist.

PMID- 1361381
TI  - [Retrospective studies on the relation between fibrocystic disease and cancer of
      the breast with therapeutic conclusions].
AB  - On the basis of 597 cases of benign and malignant tumoral, respectively
      dysplastic diseases of the breast, operated at the IInd Surgical Clinic of Tirgu
      Mures during the period 1977-1983, the authors consider the fibrocystic disease
      (FCD) of the II and III degree as a facultative precancerous lesion. The
      extremely high frequency of FCD associated to the mammary cancer in young women,
      as well as of intense epithelial proliferations and intermediate forms, of
      transition from typical epithelial hyperplasias to the atypical forms observed in
      some of these cases, is pointed out. The 4 cases (1.94%) of mammary neoplasms
      which occurred late after a mammary sectorectomy performed for FCD illustrate
      that the risk of mammary neoplasm in FCD is 7.4 times higher than the mammary
      cancer rate in women without FCD. In the extensive forms of FCD with marked
      epithelial proliferations, especially if additional risk factors are also
      present, the authors recommend a uni- or bilateral subcutaneous mastectomy, a uni
      or bilateral simple mastectomy respectively. They deem necessary the setting up,
      in all departments of general surgery, of an adequate organizational framework
      for the dispensary care, the hormonal therapy and the control of women with FCD.

PMID- 1361383
TI  - [Sclerosing cholangitis in the evolution of a surgical hepatic hydatid cyst].
AB  - The retrospective analysis of 3 clinical observations points out the
      etiopathogenetic, clinical and therapeutical aspects of the diffuse stenotic
      cholangitis, which can occur after the surgical treatment of the hepatic hydatid
      cyst. Although rare (2.9% of hydatid cysts, 13% of those which communicate with
      the bile ducts), the diffuse stenotic posthydatid cholangitis represents a severe
      postoperative complication in cases of median cysts, exerting a compression upon
      the convergence of hepatic ducts and communicating with the biliary tract. Its
      presence should be clinically suspected if a mechanical icterus with septic
      angiocholitis, sometimes associated with an external biliary fistula (from the
      residual cavity), occurs in the postoperative course of these patients,
      especially if the primary operation has excluded the remanance of an obstacle at
      the level of the main bile duct. The lesional substrate is comparable with that
      of the primitive sclerosing cholangitis, from which it differs through its clear
      relation with the primary treatment of the hepatic hydatid cyst, through the
      rapid course of stenotic lesions which, although diffuse, may become more marked
      in certain segments, as well as through the constant suprastenotic dilatation of
      the bile ducts. In the pathogenesis are involved the caustic action of some
      scolicide solutions (2 per cent formaldehyde solution, hypertonic salt solution)
      on the wall of the bile duct and the cystobiliary communication which predisposes
      to the peroperative occurrence o-a migration syndrome and of angiocholitis. It
      requires an early surgical reintervention in order to solve the cholestasis and
      angiocholitis: according to the morphological situation, we have the choice
      between disobstruction and trans-stenotic calibration drainage, on the one hand,
      and biliodigestive derivations in the hilum, which are more efficient, on the
      other. The prognosis is burdened with the vital risk of septic angiocholitis and
      with the early occurrence of a secondary biliary cirrhosis or of stenotic
      recurrences. Prophylaxis consists in the performance of a primary surgical
      treatment, adequate in median and communicating hydatid cysts, avoiding the
      "blind" intracystic administration of scolicide solutions, which exert a caustic
      action on the bile ducts.

PMID- 1361382
TI  - [Late reinterventions after the surgical treatment of gastric and duodenal
      ulcer].
AB  - A number of 87 reinterventions performed during a 5-year-period for late
      complications of the gastric and duodenal ulcer surgery are analysed. In most of
      them (64 cases), the cause of the reintervention was a postoperative ulcer. A
      long afferent loop (6 cases), the dumping syndrome (4 cases), the stenosis of the
      anastomosis opening (6 cases) and the primitive neoplasm of the gastric stump (7
      cases) represented other causes of reintervention. The immediate postoperative
      results were very good and good in 69 cases. The risks related to the specific
      character of this surgery materialized themselves in 14 postoperative
      complications (anastomotic fistulas, haemorrhages from the anastomosis, stress
      ulcers etc.), which required iterative operations; the postoperative death rate
      attained 3.4%. The analysis of these postgastrectomy syndromes is an opportunity
      to discuss about the failure factors in the surgery of the gastric and duodenal
      ulcer, the possibilities of exploration and the principles which should guide the
      reparative therapy.

PMID- 1361384
TI  - [Diverticulum of the anterior urethra. Observations on a clinical case].

PMID- 1361385
TI  - [A choledochoduodenal fistula of ulcerous origin].
AB  - The case of a 75-year-old patient is reported in whom one of the rare
      complications of the duodenal ulcer, the choledochoduodenal fistula, has occurred
      as a result of the prolonged course of this disease. The case was solved by
      "indirect treatment" of the pathologic complex, with very good results confirmed
      over time.

PMID- 1361386
TI  - [Peritonitis encapsulans, a rare cause of intestinal occlusion].

PMID- 1361388
TI  - One strong voice: call for the National Nurse Practitioner Leadership Summit.

PMID- 1361387
TI  - [A scale of anesthetic-surgical risk].
AB  - An anaesthetic and surgical risk scale, which has also a predictive power
      regarding the lethality and the probability of occurrence of postoperative
      complications, is shown. The scale scores the constitutional taints, the extent
      of the operation, the age, the eventual emergency, the special anaesthetic risk.
      A second variant scores from the constitutional viewpoint each of the 7 organ
      systems and adds a lowering of the risk in case of an operation performed upon a
      system which is directly risk generating. The lethality figure was established by
      applying the scale to 1,945 patients operated and by recording the lethality
      distribution for each risk degree, after which the function which approximates
      most accurately the data score thus obtained is evaluated by the method of the
      least squares. In this way, a direct correlation of the calculated risk with the
      actual morbidity and complication rate, as well as with the lethality in the
      group of patients with complications is obtained. As the scale is achieved by the
      analysis of patients belonging to the field of general surgery and orthopaedics,
      it is valid only for this specialty.

PMID- 1361390
TI  - Second International Conference on Race, Ethnicity, and Health: Challenges in
      Hypertension and Diabetes.

PMID- 1361389
TI  - Ecstasy and dantrolene.

PMID- 1361391
TI  - Community organization and health promotion in minority neighborhoods.

PMID- 1361392
TI  - Gastrointestinal Carcinogenesis: Risk Factors, Mechanisms and Strategies for
      Prevention. 7th Annual Symposium of the Roberto Farini Foundation for
      Gastroenterological Research. Padua, Italy, 4-5 October 1991.

PMID- 1361394
TI  - Regulatory role of brain angiotensins in the control of physiological and
      behavioral responses.
AB  - Considerable evidence now indicates that a separate and distinct renin
      angiotensin system (RAS) is present within the brain. The necessary precursors
      and enzymes required for the formation and degradation of the biologically active
      forms of angiotensins have been identified in brain tissues as have angiotensin
      binding sites. Although this brain RAS appears to be regulated independently from
      the peripheral RAS, circulating angiotensins do exert a portion of their actions
      via stimulation of brain angiotensin receptors located in circumventricular
      organs. These circumventricular organs are located in the proximity of brain
      ventricles, are richly vascularized and possess a reduced blood-brain barrier
      thus permitting accessibility by peptides. In this way the brain RAS interacts
      with other neurotransmitter and neuromodulator systems and contributes to the
      regulation of blood pressure, body fluid homeostasis, cyclicity of reproductive
      hormones and sexual behavior, and perhaps plays a role in other functions such as
      memory acquisition and recall, sensory acuity including pain perception and
      exploratory behavior. An overactive brain RAS has been identified as one of the
      factors contributing to the pathogenesis and maintenance of hypertension in the
      spontaneously hypertensive rat (SHR) model of human essential hypertension. Oral
      treatment with angiotensin-converting enzyme inhibitors, which interfere with the
      formation of angiotensin II, prevents the development of hypertension in young
      SHR by acting, at least in part, upon the brain RAS. Delivery of converting
      enzyme inhibitors or specific angiotensin receptor antagonists into the brain
      significantly reduces blood pressure in adult SHR. Thus, if the SHR is an
      appropriate model of human essential hypertension (there is controversy
      concerning its usefulness), the potential contribution of the brain RAS to this
      dysfunction must be considered during the development of future antihypertensive
      compounds.

PMID- 1361393
TI  - Histamine H2-receptor antagonists and gastric ethanol metabolism in man: effects
      on its bioavailability.

PMID- 1361395
TI  - Brain non-adenylated mRNAs.
AB  - Most eukaryotic messenger RNA (mRNA) species contain a 3'-poly(A) tract. The
      histone mRNAs are a notable exception although a subclass of histone-encoding
      mRNAs is polyadenylated. A class of mRNAs lacking a poly(A) tail would be
      expected to be less stable than poly(A)+ mRNAs and might, like the histones, have
      a half-life that varied in response to changes in the intracellular milieu. Brain
      mRNA exhibits an unusually high degree of sequence complexity; studies published
      ten years ago suggested that a large component of this complexity might be
      present in a poly(A)- mRNA population that was expressed postnatally. The
      question of the existence of a complex class of poly(A)- brain mRNAs is
      particularly tantalizing in light of the heterogeneity of brain cells and the
      possibility that the stability of these poly(A)- mRNAs might vary with changes in
      synaptic function, changing hormonal stimulation or with other modulations of
      neuronal function. The mRNA complexity analyses, although intriguing, did not
      prove the existence of the complex class of poly(A)- brain mRNAs. The observed
      mRNA complexity could have resulted from a variety of artifacts, discussed in
      more detail below. Several attempts have been made to clone members of this class
      of mRNA. This search for specific poly(A)- brain mRNAs has met with only limited
      success. Changes in mRNA polyadenylation state do occur in brain in response to
      specific physiologic stimuli; however, both the role of polyadenylation and de
      adenylation in specific neuronal activities and the existence and significance of
      poly(A)- mRNAs in brain remain unclear.

PMID- 1361396
TI  - Prostaglandins in peptic ulceration.

PMID- 1361397
TI  - Analysis of the agonist activity of fenoldopam (SKF 82526) at the vascular 5-HT2
      receptor.
AB  - 1. The 5-HT2 receptor agonist activity of fenoldopam (SKF 82526) was
      characterized in the rabbit isolated aorta preparation. 2. Fenoldopam was an
      agonist at the vascular 5-HT2 receptor with lower affinity and efficacy than the
      naturally occurring agonist 5-hydroxytryptamine (5-HT). Fenoldopam had an
      affinity (pKA) of 5.84 +/- 0.04 and efficacy (tau) of 0.57 +/- 0.04, whereas 5-HT
      had a pKA of 6.65 +/- 0.12 and tau of 2.66 +/- 0.41. 3. The constrictor effects
      of fenoldopam and 5-HT were competitively antagonized by the 5-HT2 antagonist,
      ketanserin, with pKB values of 8.81 +/- 0.11 and 8.83 +/- 0.10 respectively. 4.
      Prior incubation with fenoldopam produced a concentration-related rightward shift
      of a subsequent 5-HT concentration-response curve. This inhibition was specific
      for 5-HT since constrictor responses to angiotensin II were unaffected. 5. This
      study indicates that the D1 receptor agonist, fenoldopam, acts as an agonist at
      the vascular 5-HT2 receptor, but with an affinity and efficacy less than that of
      the naturally occurring agonist, 5-HT.

PMID- 1361398
TI  - Differential sensitivities of the prostacyclin and nitric oxide biosynthetic
      pathways to cytosolic calcium in bovine aortic endothelial cells.
AB  - 1. Bovine aortic endothelial cells were cultured in vitro, and shown to release
      both prostacyclin (PGI2; Kact = 24.1 nM) and endothelium-derived relaxing factor
      (EDRF, NO; Kact = 0.7 nM) in a concentration-dependent manner when exposed to
      bradykinin. 2. The bradykinin-dependent release of PGI2 (but not EDRF) was
      inhibited by 1 microM isoprenaline or 5 microM forskolin, and the inhibitory
      effect of isoprenaline could be reversed by the beta 2-adrenoceptor antagonist,
      ICI 118551. In contrast, isoprenaline had no capacity to inhibit PGI2 release
      stimulated by exogenous arachidonic acid. 3. Exposure of cells to bradykinin
      increased the cytosolic concentration of Ca2+ ions ([Ca2+]i; Kact = 4.8 nM), and
      the effect was inhibited by both 1 microM isoprenaline and 5 microM forskolin. 4.
      In similar experiments, exposure of cells to ionomycin also increased [Ca2+]i and
      the values of [Ca2+]i were calibrated in terms of the ionomycin concentration. In
      subsequent experiments involving exposure of endothelial cells to selected
      concentrations of ionomycin, it was possible to show that the biosynthesis of NO
      was triggered at ionomycin concentrations about one tenth of the required for
      PGI2 biosynthesis and that these corresponded to a [Ca2+]i threshold of 350 nM
      for PGI2 release while that for EDRF release was less than 200 nM. 5. These
      differences in Ca2+ ion sensitivity explain the selective inhibition of
      bradykinin-stimulated PGI2 biosynthesis (to the exclusion of NO biosynthesis) by
      isoprenaline or forskolin, both of which attenuate bradykinin-dependent increases
      in [Ca2+]i.

PMID- 1361399
TI  - Blockade by antiarrhythmic drugs of glibenclamide-sensitive K+ channels in
      Xenopus oocytes.
AB  - 1. The outward K+ current induced by KRN2391 (K+ channel opener) in Xenopus
      oocytes is blocked by glibenclamide. We have investigated the effects of various
      classes (I-IV) of antiarrhythmic drugs on this KRN2391-induced response. 2. All
      class I antiarrhythmic drugs (Na+ channel blockers) tested concentration
      dependently suppressed KRN2391-induced responses with the rank order of potency
      (IC50 in microM), disopyramide (17.8) > aprindine (29.5) > propafenone (63.1) >
      ajmaline (145) > quinidine (151). Flecainide, SUN1165, lignocaine, mexiletine and
      procainamide were much less potent (IC50, 450- > 1000 microM) than quinidine. 3.
      The class II antiarrhythmic drugs (beta-blockers), timolol, (-)- and (+/-)-
      propranolol, and (+)- propranolol (a non-beta-blocker) inhibited KRN2391-induced
      K+ currents in a concentration-dependent manner with values for IC50 (microM) of
      79, 131, 151 and 129, respectively, whilst butoxamine, oxprenolol, alprenolol,
      pindolol, nadolol, metoprolol and acebutolol were either weak (IC50, 300 microM
      600 microM) or virtually inactive (IC50, > 1000 microM). 4. The class III
      antiarrhythmic drugs, amiodarone and (+)-sotalol scarcely affected KRN2391
      responses. 5. All class IV drugs (Ca2+ antagonists) tested suppressed KRN2391
      induced responses in a concentration-dependent manner with an IC50 of 6.3 microM
      for bepridil, 38 microM for prenylamine, 85 microM for verapamil and 135 microM
      for diltiazem. 6. In conclusion, antiarrhythmic drugs of classes I, II and IV
      potently blocked glibenclamide-sensitive K+ channels in Xenopus oocytes.

PMID- 1361401
TI  - The local intracoronary administration of methylene blue prevents the pronounced
      antiarrhythmic effect of ischaemic preconditioning.
AB  - Short periods of coronary artery occlusion (2 x 5 min) markedly reduce the
      severity of arrhythmias and the changes in ST-segment elevation and in the degree
      of inhomogeneity of conduction during a subsequent 25 min occlusion of the left
      anterior descending coronary artery in anaesthetized dogs. These changes were
      completely reversed if methylene blue (5 mg min-1) was infused into a side branch
      of the coronary artery throughout both the preconditioning and prolonged
      occlusions. These results suggest that the pronounced antiarrhythmic effects of
      preconditioning result from activation of guanylyl cyclase and result in
      increased levels of guanosine 3':5'-cyclic monophosphate.

PMID- 1361403
TI  - Observations on calcium oxalate stone formers.
AB  - Biochemical studies were performed on 22 adult patients with idiopathic recurrent
      calcium oxalate renal stone disease and 23 healthy controls. It was found that
      urinary glutamic-oxaloacetic acid transaminase (UGOT) and urinary glutamic
      pyruvic acid transaminase (UGPT) activity was low and lactate dehydrogenase (LDH)
      and gamma-glutamyl transferase (gamma-GT) activity was high in the urine of
      calcium oxalate stone formers. No significant changes were observed in the
      activity of glutamic-oxaloacetic acid transaminase, glutamic-pyruvic acid
      transaminase and gamma-GT in their blood but a significant reduction was found in
      both LDH and alkaline phosphatase activity. It was concluded that the activity of
      UGOT and UGPT is reduced in patients with kidney stones.

PMID- 1361400
TI  - Subclassification of release-regulating alpha 2-autoreceptors in human brain
      cortex.
AB  - 1. Release-regulating alpha 2-autoreceptors in human brain were characterized
      pharmacologically in cortical slices from patients undergoing neurosurgery to
      remove subcortical tumours; the slices were prelabelled with [3H]-noradrenaline
      ([3H]-NA) and stimulated electrically (3 Hz, 2 ms, 24 mA) under superfusion
      conditions. 2. The stimulus-evoked tritium overflow was almost totally Ca(2+)
      dependent and tetrodotoxin-sensitive. 3. Clonidine and oxymetazoline 0.01 to 1
      microM inhibited in a concentration-dependent manner the evoked overflow of
      tritium. The two drugs were equipotent (EC50 = 0.03 microM) and their maximal
      effect was approx. 45%. Phenylephrine and methoxamine, up to 1 microM, did not
      affect tritium overflow. 4. Yohimbine (0.01-0.1 microM) shifted the concentration
      response curve of clonidine to the right. The calculated pA2 value was 8.29. 5.
      Prazosin and 2-[2-[4-(o-methoxyphenyl)piperazine-1-yl]ethyl]-4,4- dimethyl
      1,3(2H,4H)-isoquinolinedione (AR-C 239), tested at 0.3 microM, did not modify the
      concentration-response curve of clonidine. 6. The effect of clonidine was
      antagonized by (+)-mianserin (pA2 = 7.74), but not by up to 0.3 microM of the (-)
      enantiomer. The concentration-response curve of clonidine was shifted to the
      right by the novel alpha 2-adrenoceptor antagonist, 5-chloro-4-(1-butyl-1,2,5,6
      tetrahydropyridin-3-yl)-thiazole-2-ami ne (Z)-2-butenedioate (1:1) salt (ORG
      20350) (pA2 = 7.55). 7. Yohimbine, (+)-mianserin and ORG 20350, but not prazosin
      and (-)-mianserin, increased the electrically-evoked tritium overflow, suggesting
      that autoreceptors may be tonically activated by endogenous NA. 8. Desipramine (1
      microM) increased evoked tritium overflow from human cortex slices. The effect of
      clonidine (0.01- 1 g1M) on the evoked overflow of tritium was reduced in presence
      of 1 muM desipramine.9. It is proposed that autoregulation of NA release can
      occur in human cerebral cortex. The process involves activation of alpha 2
      adrenoceptors which may be either the alpha2X or the alpha2D subtype.

PMID- 1361404
TI  - Laparoscopic orchidectomy in cryptorchidism.

PMID- 1361402
TI  - Noradrenaline modulates smooth muscle activity of the isolated intravesical
      ureter of the pig through different types of adrenoceptors.
AB  - 1. We have studied the effects of alpha- and beta-adrenoceptor agonists and
      antagonists on both phasic peristaltic activity and basal tone of the isolated
      intravesical ureter of the pig by means of isometric techniques in vitro. 2.
      Spontaneous phasic activity was exhibited by 21% of pig intravesical ureter
      preparations manifested as rhythmic contractions with average frequency and
      amplitude of 2.54 +/- 0.18 min-1 and 1.48 +/- 0.16 g (n = 31), respectively. 3.
      Adrenaline, noradrenaline and phenylephrine induced concentration-dependent
      increases in both phasic activity and basal tone of ureteral preparations, all
      three agonists being more potent in modifying ureteral phasic activity than
      baseline tone. B-HT 920, B-HT 933 and clonidine had no significant effect. 4.
      Phentolamine (10(-9)-10(-7) M) and prazosin (3 x 10(-11)-3 x 10(-8) M)
      significantly inhibited increases in both frequency of phasic activity and
      baseline tone induced by a submaximal dose of noradrenaline. Rauwolscine (10(-9)
      10(-7) M) affected only the tone evoked by noradrenaline and higher
      concentrations of this antagonist were needed to block phasic activity. 5.
      Pretreatment of ureteral strips with the beta-adrenoceptor antagonist,
      propranolol (10(-6) M), significantly increased the maximum contraction evoked by
      noradrenaline. After incubation with phentolamine (10(-6) M), noradrenaline (10(
      7)-10(-6) M) decreased phasic activity induced by prostaglandin F2 alpha (10(-5)
      M). Isoprenaline and salbutamol also abolished PGF2 alpha-induced phasic
      activity. Pafenolol (10(-6) M) and butoxamine (10(-6) M) blocked the inhibitory
      effect of noradrenaline, isoprenaline, and salbutamol on PGF2 alpha-induced
      phasic activity. 6. These results suggest that noradrenaline may modulate both
      phasic peristaltic activity and basal tone of pig intravesical ureter through
      both alpha- and beta-adrenoceptors.

PMID- 1361405
TI  - Pylorus-preserving versus standard pancreaticoduodenectomy: an analysis of 110
      pancreatic and periampullary carcinomas.

PMID- 1361406
TI  - Effect of Trypanosoma vivax infection on semen characteristics of Yankasa rams.
AB  - Twelve Yankasa rams aged between 2 1/2 and 3 years with good semen
      characteristics were used in this 15-week study. Six rams were infected with
      Trypanosoma vivax, while six served as controls. The infected rams developed
      chronic trypanosomosis accompanied by fluctuating pyrexia, lethargy, anaemia,
      scrotal oedema and cachexia. There was a drastic and progressive deterioration in
      semen quality in all infected rams manifested by a decrease in volume or
      cessation of semen production, oligozoospermia, a sharp decrease in progressively
      motile sperm, elevated numbers of dead (eosinophilic) sperm and 100%
      morphological abnormalities of sperm in most animals. The rams were all deemed
      unfit for breeding by 3 weeks post-infection. Uninfected rams were healthy and
      had good semen characteristics throughout the investigation. The results show
      that rams infected with T. vivax may become infertile within a short interval due
      to rapid deterioration of semen characteristics and this trypanosome species may
      be an important causative agent of infertility in endemic areas.

PMID- 1361407
TI  - Niacinamide blocks 3-acetylpyridine toxicity of cerebellar granule cells in
      vitro.
AB  - 3-Acetylpyridine (3AP) is a potent neurotoxin when administered to laboratory
      animals. However, its neurotoxic effects have not been investigated extensively
      in vitro. Cultured cerebellar granule cells are killed by concentrations of 3AP
      of 0.1-1 mM (ED50 = 220 microM) but not by its 2-acetyl and 4-acetyl analogues.
      The toxicity of 3AP is enhanced by preexposure to subtoxic concentrations of N
      methyl-D-aspartate (NMDA) and is unaffected by the NMDA receptor antagonists MK
      801 or APV, as well as by deprenyl, mazindol, or tetrahydrofolic acid. However,
      3AP toxicity is completely blocked by preincubating cerebellar granule cells with
      low concentrations of niacinamide. These data lead us to suggest that 3AP
      toxicity is due to the substitution of 3AP for niacinamide in the formation of
      niacinamide adenine dinucleotides (NAD(P)).

PMID- 1361408
TI  - Cortically evoked excitatory synaptic transmission in the cat red nucleus is
      antagonised by D-AP5 but not by D-AP7.
AB  - Extracellular recordings were made from magnocellular red nucleus neurons (mRN)
      in alpha-chloralose (50 mg/kg, iv.) anaesthetised cats. Iontophoretically applied
      N-methyl-D-aspartate (NMDA) excited the neuronal firing which was antagonised by
      4 selective NMDA receptor antagonists: 2-amino-5-phosphonopentanoate (AP5), 2
      amino-7-phosphonoheptanoate (AP7), RS-4-(phosphonomethyl) piperazine-2-carboxylic
      acid (PMPC) and R-4-(3-phosphonopropyl) piperazine-2-carboxylic acid (CPP),
      whereas AMPA responses were uneffected. Monosynaptic excitatory responses were
      produced by stimulation of the sensorimotor cortex. These responses were reduced
      and often abolished by AP5 and PMPC but not by AP7 or CPP. It is postulated that
      two NMDA receptor subtypes exist on mRN neurones.

PMID- 1361410
TI  - The N-methyl-D-aspartate antagonist MK-801 protects against serotonin depletions
      induced by methamphetamine, 3,4-methylenedioxymethamphetamine and p
      chloroamphetamine.
AB  - The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocks
      the ability of D-methamphetamine (MA) to deplete striatal dopamine (DA). We now
      report that MK-801 attenuates decreases in serotonin (5-HT) concentration induced
      by MA and two other amphetamine analogues, 3,4-methylenedioxymethamphetamine
      (MDMA) and p-chloroamphetamine (PCA). Rats were injected with saline (1.0 ml/kg)
      or MK-801 (0.5, 1.0 or 2.5 mg/kg) followed by either saline (1.0 mg/kg), MA (4, 2
      or 1 injection(s); 10.0, 20.0 or 40.0 mg/kg), MDMA (20.0 or 40.0 mg/kg) or PCA
      (5.0 or 10.0 mg/kg). In some experiments, two injections of MK-801 or saline were
      used. Seventy-two hours after the last injection rats were sacrificed and
      concentrations of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and DA were
      determined in hippocampus and striatum. MA caused a depletion of 5-HT to 33% of
      control in hippocampus and to 50% of control in striatum after the 4 x 10.0 mg/kg
      dose regimen. When MK-801 (2.5 mg/kg) was co-administered with MA, concentrations
      of 5-HT did not differ from control levels in either brain region. MDMA depleted
      5-HT to approximately 58% of control in hippocampus and 66% of control in
      striatum at the 40 mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361409
TI  - Characterization of dynorphin-containing neurons on dissociated dentate gyrus
      cell cultures.
AB  - In the dentate gyrus, the synthesis of the opioid peptide, dynorphin, is
      modulated by a variety of stimuli. In order to elucidate the cellular and
      molecular mechanisms regulating the synthesis of dynorphin in the hippocampus, we
      have established a routine primary cell culture of dentate granule neurons and
      identified granule-like neurons by a characteristic marker, dynorphin, in these
      cultures. Cultures were prepared from 7-day-old rat pups and maintained in medium
      with 2% fetal bovine serum. These cultures contained approximately 20% neurons
      and survived for over 4 weeks. After 2 weeks in culture, neurons expressing
      dynorphin-A and its messenger RNA were detected using immunocytochemistry and in
      situ hybridization, respectively. In dentate cultures, enkephalin-,
      cholecystokinin-, neuropeptide Y- and substance P-positive cells were observed in
      addition to dynorphin-positive cells with immunocytochemistry. The results
      suggest that dentate gyrus cell cultures provide a valid in vitro model for
      studying molecular mechanisms regulating prodynorphin gene expression.

PMID- 1361411
TI  - APV prevents the elimination of transient dendritic spines on a population of
      retinal ganglion cells.
AB  - Blockade of the N-methyl-D-aspartate (NMDA) receptors on retinal ganglion cells
      (RGCs) during development prevents the elimination of the exuberant spine-like
      processes in a population of Type I RGCs in hamsters. During the development of
      RGCs, exuberant dendritic spines have been observed which disappear during
      maturation. Blocking the NMDA receptors on developing RGCs with the antagonist,
      DL-2-amino-5-phosphonovaleric acid (APV) and the subsequent retention of some of
      the normally transient dendritic spines suggest that the morphological
      development of post-synaptic neurons may be affected by this treatment. Our
      result further suggests that the elimination of exuberant spines during normal
      development requires interactions between receptors on the spines and
      neurotransmitters released by the pre-synaptic inputs.

PMID- 1361412
TI  - Long duration ventral root potentials in the neonatal rat spinal cord in vitro;
      the effects of ionotropic and metabotropic excitatory amino acid receptor
      antagonists.
AB  - Long duration, primary afferent evoked ventral root potentials (VRP's) have been
      recorded in vitro from hemisected spinal cords prepared from 8-12-day-old rat
      pups. Single shock stimulation of a dorsal root at stimulus strengths sufficient
      to recruit C/group IV afferent fibres evoked a long duration (11.9 +/- 1.2 s)
      ipsilateral VRP in all preparations. This long duration VRP consisted of two
      components, (i) a slow wave, time to peak 137.0 +/- 5.1 ms, the amplitude of
      which was reduced to 8.7% of mean control value in the presence of the N-methyl-D
      aspartate (NMDA) antagonist D-AP5 (40 microM), (ii) a prolonged wave with a time
      to peak of 2.0 +/- 0.2 s which was partially resistant to D-AP5 (40 microM). Both
      the slow and the prolonged waves were unaffected following superfusion with the
      metabotropic excitatory amino acid (EAA) receptor antagonist L-AP3 (100-200
      microM). Low frequency (1-10 Hz) repetitive stimulation (20 s duration) of high
      threshold dorsal root afferents evoked a temporal summation of synaptic activity
      which generated a progressively depolarizing VRP. This cumulative VRP was graded
      with frequency of stimulation (0.89 +/- 0.13 to 1.25 +/- 0.19 mV). The cumulative
      VRP was followed by a post-stimulus depolarization which outlasted the period of
      repetitive stimulation by tens of seconds (47.6 +/- 8.4 to 91.2 +/- 19.9 s). In
      the presence of AP5 the amplitude of the cumulative VRP was depressed to 54.5 +/-
      11.5% of control values when low frequency (1.0 Hz) stimulation was used. The
      proportion of the cumulative VRP resistant to D-AP5 increased as the frequency of
      stimulation was increased to 10 Hz. The decay time of the post-stimulus
      depolarization was unaffected by AP5. Neither the amplitude nor the post-stimulus
      depolarization of the cumulative VRP was affected by 200 microM L-AP3. It is
      suggested that both an AP5 sensitive and AP5 insensitive potential contribute to
      the long duration VRP evoked in the neonatal rat spinal cord following single
      shock high threshold afferent stimulation. Moreover, the AP5 insensitive
      prolonged depolarization is manifest following sustained low frequency stimuli
      and higher frequency inputs.

PMID- 1361413
TI  - Tyrosine augments dopamine release in stimulated rat retina.
AB  - Endogenous dopamine (DA) release was measured in perfused rat retinae. Perfusion
      with elevated potassium (40 mM K) resulted in a 5-6-fold increase in DA release
      over baseline or 11.6 +/- 0.9% of final tissue DA content. When the selective DA
      D2 receptor agonist quinpirole was added to the perfusion medium (at 1 and 10
      microM), K-stimulated DA release was significant decreased compared to controls
      (to 7.0 +/- 1.6 and 6.14 +/- 1.4%, respectively). Addition of the D2 antagonist
      (+/-)-sulpiride (10 microM) significantly increased DA release to 19.1 +/- 1.3%.
      DA could be released with successive pulses of K; an initial 10 min pulse
      resulted in a 4-5-fold increase in endogenous DA release over basal levels or
      11.4% of the final retinal tissue DA content and a 3-fold increase (a 9.3%
      fractional release) upon a second K stimulation given 50 min later. The ratio of
      stimulated DA release during the two K pulses was 0.82 +/- 0.04. When L-tyrosine
      (100 microM) was included in the medium throughout the perfusion, K2/K1 was
      increased to 1.14 +/- 0.13. Both tissue DA level and release were decreased by
      the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (AMPT). At 10 microM
      AMPT K-stimulated DA release was reduced by 50% during the first pulse and
      completely abolished during the second K pulse. At 100 microM both basal and K
      stimulated release were significantly reduced. Exposure of dark-adapted retinae
      to light in L-tyrosine-supplemented perfusion medium resulted in an increased
      release of DA compared to retinae perfused with tyrosine-free medium.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1361414
TI  - Contribution of the central interaction between calcium and sodium to hemodynamic
      regulation in spontaneously hypertensive rats.
AB  - The contribution of the central interaction between calcium and sodium to
      hemodynamic regulation was assessed in spontaneously hypertensive rats (SHRs) and
      Wistar-Kyoto (WKY) rats. The effect of a high calcium solution (Ca2+, 130 mg/dl,
      10 microliters) infused into the cerebral ventricle (i.c.v.) on hemodynamic
      responses induced by a high sodium solution (Na+, 1,000 mEq/1, 10 microliters)
      i.c.v. and the mechanism by which high Ca2+ affects the hemodynamic responses
      induced by high Na+ i.c.v. were studied. High Na+ i.c.v. induced a pressor
      response with tachycardia in the SHRs, but induced a pressor response with reflex
      bradycardia in the WKYs. Prior treatment with high Ca2+ i.c.v. attenuated the
      pressor response induced by high Na+ i.c.v. (+55.6 +/- 4.4 to +33.1 +/- 3.2 mmHg,
      P < 0.01) and restored reflex bradycardia (+86.4 +/- 7.7 to -26.7 +/- 7.6 bpm, P
      < 0.01) in SHRs. Whereas prior treatment with high Ca2+ i.c.v. attenuated the
      pressor response (+35.7 +/- 2.0 to +22.2 +/- 4.0 mmHg, P < 0.05), it did not
      alter the degree of reflex bradycardia (-81.7 +/- 7.1 to -69.2 +/- 120 bpm, n.s.)
      in WKYs. Ganglionic blockade attenuated the pressor response (+56.9 +/- 3.5 to
      +42.9 +/- 2.3 mmHg, P < 0.05) and restored reflex bradycardia (+82.1 +/- 10.3 to 
      65.9 +/- 11.0 bpm, P < 0.01) in SHRs, whereas, inhibition of arginine vasopressin
      attenuated the pressor response without modification of the tachycardic
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361415
TI  - Effects of glucose and fat antimetabolites on norepinephrine turnover in rat
      hypothalamus and brainstem.
AB  - Rats were injected acutely with antimetabolites of either glucose (2 deoxy-D
      glucose, 2DG), fat (methylpalmoxirate, MP or mercaptoacetate, MAC), or the
      combination of these agents, in dosages known to stimulate food intake.
      Norepinephrine (NE) turnover in hypothalamus and brainstem was determined after
      these treatments by the method of synthesis inhibition. Glucoprivation (2DG)
      increased NE turnover in hypothalamus, confirming previous studies. Fat
      antimetabolites alone had no effect on NE turnover, nor did a peripherally-acting
      fructose antimetabolite. Combination of MP and 2DG, but not MAC and 2DG, produced
      a greater NE turnover than 2DG alone. These data suggest that peripheral signals
      of metabolic emergency do not activate brain NE systems, except when these
      systems are already activated by an ongoing cerebral metabolic emergency. The
      role of hypothalamic NE in metabolic integration of feeding is discussed, and
      possible hemispheric differences.

PMID- 1361416
TI  - NMDA receptor mediates dopamine release in the striatum of unanesthetized rats as
      measured by brain microdialysis.
AB  - We have studied the characteristics associated with the activation of the N
      methyl-D-aspartate (NMDA) subtype of the glutamate receptor on the release of
      dopamine (DA) in the striatum of awake rats as measured by brain microdialysis
      technique. NMDA dose-dependently stimulated the striatal DA release in Mg(2+)
      free Ringer's solution. The stimulation was significant at 90 microM and the
      maximum observed effect was at the highest concentration tested (800 microM). The
      selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate (AP5; 300
      microM), blocked the stimulatory effect of NMDA. The NMDA-induced release of DA
      was reduced by 1.2 mM Mg2+ and totally blocked by 2.5 mM of the cation. Glycine
      (200 microM) potentiated the response evoked by 300 microM NMDA while 7-chloro
      kynurenate (100 microM), an antagonist of the glycine site, reduced markedly this
      response. Neither atropine (100 microM) nor tetrodotoxin (TTX) (5 microM)
      prevented the stimulatory effect of NMDA. These results suggest that glutamate
      released from corticostriatal terminals presynaptically stimulates the release of
      DA via an NMDA receptor.

PMID- 1361417
TI  - NMDA receptors assessed by autoradiography with [3H]L-689,560 are present but not
      enriched on corticofugal-projecting pyramidal neurones.
AB  - Experimental lesions followed by binding of [3H]4-trans-2-carboxy-5,7-dichloro-4
      phenylamino-carbonylamino-1,2 ,3,4- tetrahydroquinoline ([3H]L-689,560, a novel
      ligand that binds to the glycine modulatory site), [3H]glycine and [3H]glutamate
      (N-methyl-D-aspartate (NMDA) sensitive) to cryostat sections and quantitative
      autoradiography were used to investigate the cellular localization of the NMDA
      receptor complex in the neocortex of the rat. The lesions were produced by
      intrastriatal injections of either volkensin (2 and 6 ng) or ricin (10 ng): both
      are suicide transport agents but only the former is retrogradely transported in
      the CNS. The binding of [3H]L-689,560 was significantly reduced in rats receiving
      2 or 6 ng volkensin in deep cortical layers of Fr1/Fr2 ipsilateral to the
      striatal lesion. Similar reductions were also seen in [3H]glycine and
      [3H]glutamate binding, but only in rats receiving 6 ng volkensin. Quantitative
      histological analysis had previously revealed a loss of large infragranular
      pyramidal neurones with sparing of both interneurones and supragranular pyramidal
      neurones. There were no significant reductions in binding of any ligand in the
      superficial layers. In cortical areas Par1/Par2, [3H]L-689,560 was also
      significantly reduced in deep layers but only in rats receiving 6 ng volkensin.
      Binding was also reduced in the superficial layers by contrast to Fr1/Fr2.
      [3H]Glycine and [3H]glutamate binding were unaffected in this area. Binding of
      [3H]L-689,560 was unaffected in any area following intrastriatal ricin injection.
      The present study indicates that the NMDA receptor complex is present on
      pyramidal cells forming the corticofugal pathways. This is discussed in terms of
      the 5-HT1A receptor which is enriched on these cells.

PMID- 1361418
TI  - Inhibition of spinal opioid analgesia by supraspinal administration of selective
      opioid antagonists.
AB  - The effect of intracerebroventricular administration of a selective mu- (CTOP) or
      delta- (ICI 174,864) opioid receptor antagonist on the antinociceptive effects
      produced by intrathecal administration of selective mu- (DAMGO), delta- (DPDPE)
      and kappa- (U50-488H) opioid receptor agonists was evaluated using the Randall
      Selitto paw-withdrawal test, in the rat. While the intracerebroventricular
      administration of CTOP or ICI 174,864, alone, had no effect on nociceptive
      thresholds, intracerebroventricular administration of CTOP and ICI 174,864
      produced marked antagonism of the antinociceptive effects of intrathecal DAMGO.
      The antinociceptive effects of intrathecal administration of DPDPE or U50,488H
      were not antagonized by intracerebroventricular administration of CTOP or ICI
      174,864. These data suggest that, in the rat, along with the established
      descending antinociceptive pathways, there is an ascending antinociceptive
      control mechanism projecting from the spinal cord to the brainstem. The ascending
      antinociceptive control involves mu- and delta-opioid agonism at supraspinal
      sites and appears to be mediated selectively by mu-, but not by delta- or kappa
      opioid agonism at the spinal level.

PMID- 1361419
TI  - Effect of the neurotoxin AF64A on intrinsic and extrinsic neuronal systems of rat
      neostriatum measured by in vivo microdialysis.
AB  - In the present in vivo microdialysis study the aziridinium ion of ethylcholine
      mustard, AF64A and the excitotoxin ibotenic acid were compared for their effects
      on extracellular striatal acetylcholine, choline, gamma-aminobutyric acid (GABA),
      dopamine and its metabolites, glutamate and aspartate, measured in the same
      perfusate sample, under basal and high KCL conditions. Ten days following
      unilateral striatal injections of AF64A (2 x 0.08 to 2 x 8 mM) there was a dose
      dependent decrease in the extracellular striatal levels of acetylcholine and
      GABA, the two major intrinsic striatal neurotransmitter systems. No significant
      effects were observed on any of the monitored neurotransmitter systems following
      the lowest (2 x 0.08 mM) dose of AF64A, while at the intermediate (2 x 0.8 mM)
      dose, AF64A produced a unilateral > 50% and > 70% decrease in basal extracellular
      striatal acetylcholine and GABA levels respectively. The effects of K(+)
      depolarization on extracellular acetylcholine and GABA levels were diminished by
      approximately 50%. At the highest dose (2 x 8 mM), extracellular striatal
      acetylcholine levels were non-detectable under basal conditions, while the GABA
      levels were decreased by > 50%, when compared with the contralateral intact side.
      However, at this dose, GABA levels were bilaterally decreased compared to levels
      observed in control animals. Basal extracellular striatal dopamine and glutamate
      levels, representing the two major extrinsic neurotransmitter systems innervating
      the neostriatum were only affected by the highest dose of AF64A. The excitotoxin
      ibotenic acid (2 x 28.4 mM) produced a strong unilateral decrease in
      extracellular striatal acetylcholine (> 80%) and GABA (> 90%) levels, without
      significantly affecting basal dopamine and glutamate levels.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1361421
TI  - [Interactions between GABAergic and cholinergic mechanisms involved in monocular
      optokinetic nystagmus in frogs].
AB  - The systemic administration of atropine, a muscarinic cholinergic antagonist, was
      found to suppress the Nasal-Temporal (N-T) component of the frog monocular
      optokinetic nystagmus (OKN), which had appeared following a prior injection of
      bicuculline and which does not exist in the normal animal. On the contrary, the
      administration of a nicotinic cholinergic antagonist (D-TC, alpha-BGT,
      Hexamethonium) following that of bicuculline has prolonged the duration of the
      induced N-T component. Thus, ACh was shown to attenuate or to reinforce the
      GABAergic inhibition of the N-T component through muscarinic receptors or
      nicotinic receptors respectively. These data point to the existence of strong
      interactions between these two neurotransmission systems involved in frog
      monocular OKN.

PMID- 1361420
TI  - Dependence of carotid chemosensory responses on metabolic substrates.
AB  - The dependence of the carotid chemosensory response to hypoxia on metabolic
      substrate and the hypothesis that lactic acidosis is essential for O2
      chemoreception were tested. Effects of 3 types of substrate (glucose, glutamate
      and a mixture of amino acids) on the response to hypoxia (perfusate flow
      interruption) were measured (n = 33 carotid bodies). The response to nicotine (n
      = 25) was used to determine whether these effects were exclusive to the hypoxic
      response. The cat carotid body was perfused and superfused in vitro with modified
      Tyrode solution (pO2 > 400 Torr, pCO2 < 1 Torr, pH = 7.4) at 36 degrees C
      containing a given substrate for at least 15 min prior to flow interruption or
      nicotine injection. Without substrate, responses to flow interruption (n = 4) and
      nicotine (n = 2) were irreversibly depressed. With glucose, responses to flow
      interruption (n = 13) and nicotine (n = 8) increased in a concentration-dependent
      fashion. Glutamate (42 mM) alone (n = 11) or a mixture of amino acids (4.2 mM)
      plus 5.5 mM glucose (n = 12) substituted for 11 mM glucose (n = 10). Thus,
      glutamate (42 mM), or a mixture of amino acids (4.2 mM) or a high concentration
      of glucose (11 mM) can support chemosensory responses to flow interruption and
      nicotine. Since glutamate undergoes oxidative deamination to alpha-ketoglutarate
      without lactic acid production, O2 chemoreception does not depend on lactic
      acidosis.

PMID- 1361422
TI  - Rehabilitation Outcome Measures Conference. Edmonton, Alberta, Canada, October 17
      19, 1991.

PMID- 1361423
TI  - Diagnostic value of a P-fimbriation test in determining duration of therapy in
      children with urinary tract infections.
AB  - The patients were 117 children (aged 4 months to 14 years) with uncomplicated
      urinary tract infections caused by co-trimoxazole-sensitive Escherichia coli. The
      patients were randomly assigned to receive treatment with co-trimoxazole for 3
      days (n = 58) or 7 days (n = 59). Urine was analyzed for bacteria before and
      immediately after treatment and again at 1 and 2 months. After 3 days' treatment,
      infection persisted in 14 of 31 patients with P-fimbriated strains of E coli and
      in 1 of 27 patients with non-P-fimbriated strains. After 7 days' treatment,
      infection persisted in 2 of 40 patients with fimbriated strains and in none of
      the 19 patients with nonfimbriated strains. One or 2 months after treatment, 3
      days' treatment was rated successful in 26 of 27 patients with nonfimbriated
      strains and in none of the patients with fimbriated strains. Seven days'
      treatment was rated successful in all patients with nonfimbriated strains and in
      32 of 40 patients with fimbriated strains. The results indicate that the length
      of treatment of urinary tract infections in children should be adjusted according
      to the presence of bacterial P-fimbriae in addition to the patients' clinical
      condition.

PMID- 1361424
TI  - The presence of immunoreactive vertebrate bioactive peptide substances in
      hemocytes of the freshwater snail Viviparus ater (Gastropoda, Prosobranchia).
AB  - 1. Using an immunocytochemical procedure a wide range of immunoreactive
      vertebrate bioactive peptides (BAPs) has been found in hemocytes of Viviparus
      ater: bombesin, calcitonin, CCK-8, CCK-39, GH, glucagon, insulin, oxytocin,
      neurotensin, secretin, serotonin, somatostatin, substance P, vasopressin, and
      VIP. 2. No immunostaining was observed for antigastrin and antithyroglobulin
      antibodies. 3. The presence of BAP-like molecules in hemocytes suggests a
      correlation between hemocyte and APUD cells and is evidence of a relationship
      between the neuroendocrine and the immune systems.

PMID- 1361425
TI  - Nontraditional combination pharmacotherapy of hypertension.
AB  - Traditional drug combinations that have additive hypotensive effect include
      double therapy with a diuretic and any other antihypertensive agent and triple
      therapy with a diuretic, direct vasodilator, and either a beta blocker or
      reserpine. Due to the availability of new classes of antihypertensive agents,
      other combinations of drugs are now increasingly used. The effectiveness of
      combination therapy for hypertension has been investigated; the results of these
      studies are reviewed.

PMID- 1361427
TI  - Suicide risk associated with drug and alcohol addiction.
AB  - The association of alcohol and drugs with suicidal thinking and behavior is both
      causal and conducive. The subjective state of hopelessness is key to the
      disposition to actual suicide. Alcohol and drugs are influential in providing a
      feeling of hopelessness by their toxic effects, by disruption of interpersonal
      relationships and social supports, and, possibly, by manipulating
      neurotransmitters responsible for mood and judgment. Because alcoholism and drug
      addiction are leading risk factors for suicide and suicidal behavior, any
      alcoholic or drug addict should be assessed for suicide, especially if actively
      using alcohol or drugs.

PMID- 1361428
TI  - [Immunoglobulins in Therapy. 27 October 1991].

PMID- 1361426
TI  - Urticaria and angioedema.
AB  - Urticaria and angioedema are commonly seen in the outpatient setting. Their
      pathogenesis involves complex cellular and humoral factors. Diagnosis depends on
      historical information such as duration of symptoms, exacerbating factors, and
      atopy. While many etiologic factors have been implicated, in most chronic cases
      no specific etiology is found. This article reviews physical and hereditary
      syndromes and discusses therapeutic regimens based on the duration and severity
      of symptoms.

PMID- 1361429
TI  - Myocardial uptake and effects of glutamate during non-ischaemic and ischaemic
      conditions. A clinical study with special reference to possible
      interrelationships between glutamate and myocardial utilization of carbohydrate
      substrates.

PMID- 1361430
TI  - Diabetes and Exercise '90. World Health Organization symposium. Dusseldorf,
      Germany, 19-21 May 1990.

PMID- 1361431
TI  - Inhibition of respiratory burst activity in alveolar macrophages by
      bisbenzylisoquinoline alkaloids: characterization of drug-cell interaction.
AB  - The objective of this study was to investigate the effects of various
      bisbenzylisoquinoline (BBIQ) alkaloids on respiratory burst activity of alveolar
      macrophages and to characterize the interaction of these drugs with alveolar
      phagocytes. BBIQ alkaloids were chosen for study because they exhibit a wide
      range of antifibrotic potencies in a rat model, with tetrandrine being very
      effective and tubocurarine being ineffective. These drugs inhibited zymosan
      stimulated oxygen consumption with a potency sequence of tetrandrine (TT)
      approximately fangchinoline (FA) > berbamine (BE) approximately cepharanthine
      (CE) approximately cycleanine (CY) >> tubocurarine (TU). This inhibition of
      respiratory burst activity could not be attributed to a drug-induced decline in
      the ATP content of these pneumocytes. Drug binding to alveolar macrophages was
      directly dependent on temperature and drug concentration. The sequence for
      binding capacity was FA > TT approximately BE approximately CY > CE >> TU.
      Therefore, there was no simple relationship between binding capacity and
      inhibitory potency. Binding capacity was not related to lipophilicity of these
      alkaloids. In addition, tetrandrine failed to bind to metabolically dead cells or
      sonicated macrophage preparations. These data suggest that the interaction of
      BBIQ alkaloids with phagocytes is not simply nonspecific binding to membrane
      lipids. Alteration of the cytoskeletal system with vinblastine, taxol, or
      cytochalasin B decreased tetrandrine binding by approximately 33% when added
      separately and by 93% when added jointly. Pre-exposure of alveolar macrophages to
      stimulants increased the ability of BBIQ alkaloids to inhibit both oxygen
      consumption and superoxide release. These data suggest that the mechanism by
      which BBIQ alkaloids inhibit activation of phagocytes involves microtubules and
      bules and microfilaments. Pre-exposure of macrophages to stimulants would change
      the conformation of cytoskeletal components and may make these structures more
      susceptible to drug interaction.

PMID- 1361432
TI  - Gonocytes of male rats resume migratory activity postnatally.
AB  - In the testis of the neonatal rat, maturation of germ cells, or gonocytes, lays
      the foundations for spermatogenesis which will begin later in postnatal
      development. One of the most critical and yet least understood of the events that
      occur during the immediate neonatal period is relocation of gonocytes from the
      more central part of the seminiferous cord, where they are surrounded by Sertoli
      cells, to its periphery, where they contact the basement membrane. For the
      current study, we examined this change in gonocyte position by identifying some
      of the cellular mechanism involved, with the aim of determining whether movement
      of gonocytes to the basement membrane in vivo and development of cellular
      processes by these cells in vitro represents a resumption of migratory activity
      similar to that displayed by their fetal ancestors and by other motile cells.
      First, we used either thiamine pyrophosphatase cytochemistry or the fluorescent
      probe nitrobenzoxadiazole ceramide to visualize the Golgi complex in gonocytes
      and found that (1) this organelle matures and apparently enlarges in vivo with a
      time course paralleling movement of gonocytes to the basement membrane and
      undergoes similar changes in vitro that correlate with gonocyte process
      formation, and (2) the Golgi complex is located in perinuclear cytoplasm facing
      the apparent direction of gonocyte movement in vivo and in cytoplasm near the
      cellular process in the great majority of elongated gonocytes in coculture. Next
      we used two drugs, brefeldin A and monensin, which have in common their ability
      to disrupt the Golgi complex, and found that both drugs prevent process formation
      by gonocytes in a manner that is completely reversible. We also tested the
      involvement of the cytoskeleton in gonocyte elongation by utilizing nocodazole to
      disrupt and taxol to stabilize microtubules, as verified by alpha-tubulin
      immunofluorescence. Inclusion of the drug abolished (taxol) or substantially
      diminished (nocodazole) the ability of gonocytes to elongate in a reversible
      manner. We also found that the Golgi complex was intact in the presence of taxol
      and that microtubules were intact in the presence of both Golgi complex-specific
      drugs. Thus, our findings indicate that (1) both the Golgi complex and
      microtubules are involved in development of processes by gonocytes and (2)
      neither structure is sufficient by itself to allow these cells to elongate. Taken
      together, our data provide new evidence suggesting that the cellular mechanism
      utilized by postnatal gonocytes in relocating to the basement membrane are those
      mediating active migration.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1361433
TI  - An amphicrine pancreatic cell line: AR42J cells combine exocrine and
      neuroendocrine properties.
AB  - The permanent cell culture line AR42J, derived from a rat pancreatic acinar
      carcinoma, is widely used for functional studies of exocrine pancreatic acinar
      cells. We now present evidence that these cells are amphicrine in that they
      contain zymogen granules as well as small (40-80 nm) neuroendocrine (NE) vesicles
      and typical neurotransmitters. Using the small NE vesicle-specific markers
      synaptophysin and "protein S.V.2", including synaptophysin cDNA probes, we have
      found that AR42J cells synthesize these proteins and contain vesicles harboring
      these proteins with biophysical properties similar to those of small NE vesicles.
      NE properties of these cells are further indicated by the presence of
      considerable amounts of stored amino acids (gamma-aminobutyric acid (GABA),
      glycine, glutamate) and by the presence of the GABA-synthesizing enzyme, glutamic
      acid decarboxylase. Finally, intermediate filament (IF) protein typing showed
      only cytokeratins 8 and 18, indicating that AR42J cells possess an IF protein
      complement indistinguishable from that of acinar and islet cells. Our results
      document the unusual case of a permanent cell line with combined exocrine and
      neuroendocrine properties that may be indicative of a derivation from a cell with
      multipotential character.

PMID- 1361435
TI  - Research in 'prostatitis syndromes': the use of alfuzosin (a new alpha 1-receptor
      blocking agent) in patients mainly presenting with micturition complaints of an
      irritative nature and confirmed urodynamic abnormalities.
AB  - A double-blind, placebo-controlled study in 20 patients with 'prostatitis
      syndromes' and confirmed urodynamic abnormalities using the alpha 1-receptor
      blocking compound alfuzosin is reported. Flow rate recordings are probably the
      most reliable and useful objective variables in this type of investigation. There
      is a significant beneficial effect in the group using an active compound
      concerning maximal flow (p = 0.01), flow time (p = 0.03) and time to maximal flow
      (p = 0.01). However, compared with the group using a placebo, only the change in
      the maximal flow rate appeared to be significantly different. Subjective effects
      were more pronounced in the alfuzosin group, but the spurious nature of the
      subjective observations is stressed. Based on objective parameters, alfuzosin
      seems to be effective compared to placebo in the treatment of these patients with
      micturition complaints of an irritative nature and urodynamic abnormalities,
      while only minor side effects were noticed.

PMID- 1361434
TI  - Molecular detection of genetic defects in congenital adrenal hyperplasia due to
      21-hydroxylase deficiency: a study of 27 families.
AB  - Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OHase) deficiency
      is inherited as an autosomal recessive trait. Patients can present with the salt
      wasting, simple virilizing or a non-classical form of the disease. The gene for
      P450C21, the enzyme carrying 21-OHase activity, has been mapped to the major
      histocompatibility complex on chromosome 6p. Using molecular hybridisation
      techniques we have studied the genetic defect in 27 families with one or more
      affected offspring diagnosed and treated at the University Hospital of Essen. DNA
      samples were digested with restriction endonuclease TaqI, PvuII, BglII, and EcoRI
      and analysed by Southern blot hybridisation with the cDNA probe pC21/3c. Eleven
      of 40 haplotypes associated with the salt wasting form were found to have a large
      deletion of 30 kb affecting the 5' end of the active 21-OHase gene and the 3' end
      of the closely linked pseudogene. Results in another 11 cases are compatible with
      gene conversion; 18 cases were not informative. The 30 kb deletion was associated
      with a combination of the HLA antigens Bw47 and DR7 in 7 of 11 cases. In the
      haplotypes with gene conversion, no linkage disequilibrium to HLA antigens was
      found. No apparent gene alterations were detected in simple virilizing and non
      classical haplotypes. The direct detection of the genetic defect in 55% of the
      salt wasting haplotypes may help to improve predictive testing in families with
      CAH.

PMID- 1361436
TI  - Comparative assessment of proliferating cell nuclear antigen immunostaining and
      of nucleolar organizer region staining in transitional cell carcinomas of the
      urinary bladder. Correlation with other conventional prognostic pathologic
      parameters.
AB  - The expression of two cell proliferation indices, the proliferating cell nuclear
      antigen (PCNA), using the monoclonal antibody PC-10 in the immunoperoxidase
      method, and the nucleolar organizer regions (NORs), using the colloid silver
      nitrate staining technique, was assessed in formalin-fixed paraffin-embedded
      material of 50 transitional cell urinary bladder carcinomas. A relationship was
      found between the histologic grade and each of the two indices used. A
      significant difference was observed, particularly between carcinomas of grade II
      and III (p < 0.001). A relationship was also demonstrated between each of PC-10
      and AgNOR scores and the clinical stage, but it was attributed mostly to the
      close correlation of the latter with the histologic grade of these tumors. The
      linear correlation coefficient between PC-10 and AgNOR scores was 0.757 (p <
      0.001). Our results suggest that PC-10 and AgNOR scores may be important
      prognostic indices in urinary bladder cancer.

PMID- 1361437
TI  - Uptake of radioligands by rat heart and lung in vivo: CGP 12177 does and CGP
      26505 does not reflect binding to beta-adrenoceptors.
AB  - The biodistribution of (-)-4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H
      benzimidazol-2-one (CGP12177, a non-selective beta-adrenoceptor antagonist) and 1
      [2-(3-carbamoyl-4-hydroxy)-(5-3H-phenoxy)]-2-propanol methanesulfonate,
      (CGP26505, a beta 1-adrenoceptor antagonist) was studied in rats pretreated with
      various alpha- and beta-adrenoceptor blocking drugs (5 min before 3H injection,
      in dosages at which the drugs demonstrated the expected selectivity). Cardiac and
      pulmonary radioactivity were measured after 10 min, when specific binding was
      maximal. Uptake of [3H]CGP12177 was linked to binding to beta-adrenoceptors since
      it was not affected by prazosin or yohimbine, and was equally well inhibited by
      propranolol, unlabelled CGP12177 and isoprenaline. Moreover, atenolol and
      CGP20712A inhibited [3H]CGP12177 uptake in heart (predominantly beta 1
      adrenoceptors) more potently than ICI 118,551, while in lungs (predominantly beta
      2-adrenoceptors) ICI 118,551 was more potent than atenolol or CGP20712A. In
      contrast, [3H]CGP26505 uptake in the target organs was equally effectively
      inhibited by propranolol and ICI 118,551, and significantly lowered by alpha
      adrenoceptor antagonists. We conclude that [11C]CGP12177, but not [11C]CGP2605
      will be suitable for positron emission tomography imaging of beta-adrenoceptors
      in animals.

PMID- 1361438
TI  - Antagonism of vecuronium by one of its metabolites in vitro.
AB  - The neuromuscular-blocking agent vecuronium bromide undergoes hydrolysis to three
      pharmacologically active metabolites (3-desacetyl, 17-desacetyl and 3,17
      desacetyl vecuronium) which might modify the neuromuscular-blocking action of
      their parent compound. In order to elucidate the possible role of the interaction
      between vecuronium and its metabolites in the complications reported after long
      term use of vecuronium in intensive care unit (ICU) patients, the relative
      potency of vecuronium, 3-desacetyl and 3,17-desacetyl vecuronium was determined
      in the rat hemidiaphragm in vitro and the mode of interaction of the above
      mentioned compounds investigated. Dose-response relationships were established
      for each substance alone and for combinations of vecuronium with its metabolites.
      The relative potency at the EDmax50 levels (% maximal effect) were in the order
      of 1:1.2:27 for vecuronium, the 3-desacetyl derivative and the 3,17-desacetyl
      derivative, respectively. The mode of interaction characterized by isobolographic
      and algebraic (functional) analysis showed vecuronium and 3-desacetyl vecuronium
      to interact in an additive fashion while the combined effect of the parent
      compound and its 3,17-desacetyl derivative was less than additive, indicating
      antagonism.

PMID- 1361440
TI  - Attenuation of the inhibitory effect of dynorphin on dopamine release in the rat
      nucleus accumbens by repeated treatment with methamphetamine.
AB  - Dynorphin (1-100 nM) dose dependently inhibited both spontaneous and electrically
      evoked endogenous dopamine (DA) release from slices of the nucleus accumbens of
      untreated rats. When this inhibitory effect was compared, it was significantly
      reduced in rats pretreated (for 9 days) with methamphetamine (6 mg/kg per day
      i.p.) relative to rats treated with saline. These findings indicate that
      dynorphin inhibits DA release from the nucleus accumbens, and that treatment with
      methamphetamine reduces the modulatory action of dynorphin on DA release. It is
      possible that repeated administration of methamphetamine leads to attenuation of
      the inhibition of DA release from the nucleus accumbens via presynaptic dynorphin
      sensitive receptors.

PMID- 1361439
TI  - Stimulation by corticotropin-releasing factor of the release of immunoreactive
      dynorphin A from mouse spinal cords in vitro.
AB  - Corticotropin-releasing factor (CRF) has been shown to release endogenous opioid
      peptides from several rat brain regions. Since we have demonstrated previously
      that the actions produced by intrathecally administered CRF in mice involve
      spinal kappa opioid receptors, experiments were conducted in this study to test
      the possibility that CRF may release dynorphin A, a putative endogenous kappa
      opioid agonist, from the mouse spinal cord. Using a superfusion system in vitro,
      mouse spinal cords were superfused with aerated (95% O2, 5% CO2) Krebs-Ringer
      buffer. Fractions of superfusion were collected and dynorphin A levels in each
      fraction were monitored by radioimmunoassay. The presence of CRF in the perfusion
      buffer stimulated significantly the release of immunoreactive dynorphin A. The
      releasing rate of immunoreactive dynorphin A returned to the basal level after
      withdrawing CRF from the superfusion buffer. The stimulatory effect of CRF on the
      release of immunoreactive dynorphin A was abolished by alpha-helical CRF-(9-41),
      a CRF receptor antagonist, indicating that the dynorphin-releasing effect of CRF
      was mediated by CRF receptors in the spinal cord. Also the dynorphin-releasing
      effect of CRF was a concentration-related phenomenon, with an estimated EC50
      value of 5.3 nM. The results from this study support the hypothesis that
      intrathecally administered CRF may produce its effects by releasing endogenous
      dynorphin from the terminals of dynorphin-containing neurons in the spinal cord.
      This study also provides evidence to support the notion that there is a close
      communication between CRF- and opioid peptide-containing neuronal pathways in the
      central nervous system.

PMID- 1361442
TI  - Multidimensional behavioral analyses show dynorphin A-(1-13) modulation of
      methamphetamine-induced behaviors in mice.
AB  - The effects of intracerebroventricular (i.c.v.) injection of dynorphin A-(1-13)
      on methamphetamine-induced behavioral alterations in mice were determined by
      using multidimensional behavioral analyses. Methamphetamine (0.3, 1.0 and 3.0
      mg/kg s.c.) produced a marked increase in linear locomotion, circling, rearing
      and/or grooming behaviors. The behavioral effects of methamphetamine (1.0 mg/kg
      s.c.) were almost completely antagonized by pretreatment with the dopamine D2
      receptor antagonist, S(-)-sulpiride (3.0 and/or 10.0 mg/kg i.p.), but not with
      the dopamine D1 receptor antagonist, SCH 23390 (0.01 or 0.03 mg/kg i.p.).
      Although dynorphin A-(1-13) (3.0 or 12.5 micrograms i.c.v.) alone did not produce
      any significant effects on behavior, the methamphetamine (1.0 mg/kg s.c.)-induced
      increase in circling ipsilateral to the injection side was markedly enhanced by
      dynorphin A-(1-13) (12.5 micrograms i.c.v.). In contrast, the peptide (12.5
      micrograms i.c.v.) inhibited the methamphetamine (1.0 mg/kg s.c.)-induced
      increase in rearing, whilst the increase in grooming remained unchanged. The
      effects of dynorphin A-(1-13) (12.5 micrograms i.c.v.) were fully reversed by the
      opioid antagonist, Mr 2266 (5.6 mg/kg s.c.). These results suggest that the
      unilateral administration (i.c.v.) of dynorphin A-(1-13) inhibits the activity of
      dopamine-elicited neurotransmission, resulting in an increase in ipsilateral
      circling and in a decrease in rearing.

PMID- 1361441
TI  - Mixed agonist-antagonist properties of umespirone at neostriatal dopamine
      receptors in relation to its behavioral effects in the rat.
AB  - In normal rats treated with the inhibitor of cerebral decarboxylase, NSD-1015
      (100 mg kg-1 i.p.), umespirone (1.9-30.0 mumol kg-1 s.c.) produced an increase in
      neostriatal DOPA (dihydroxyphenylalanine) accumulation, whereas decreased DOPA
      accumulation was obtained in reserpine-pretreated (5 mg kg-1 s.c., -18 h)
      animals. The latter effect was statistically significant only in the ventral,
      limbic, portion of the neostriatum. Neostriatal 5-hydroxytryptophan (5-HTP)
      accumulation was decreased in the reserpine-treated animals but not in normal
      controls. DOPA accumulation in the neocortex was not affected by umespirone
      treatment in either preparation, whereas 5-HTP accumulation was decreased in the
      reserpine-treated animals. Spontaneous locomotor activity was suppressed by
      umespirone at doses that did not affect treadmill locomotion (7.9-31.2 mumol kg-1
      s.c., -30 min), and there were no signs of catalepsy at doses ranging from 31.2
      249.6 mumol kg-1 s.c. up to 2 h after injection. Thus, umespirone behaves as a
      mixed dopamine receptor agonist/antagonist and also displays 5-HT receptor
      agonist properties. This biochemical profile was associated with sedation, as
      observed in the open-field, at doses which did not affect treadmill locomotion or
      induced catalepsy.

PMID- 1361443
TI  - Transmitter-like 3,4-dihydroxyphenylalanine is tonically released by nicotine in
      striata of conscious rats.
AB  - Microdialysis and high performance liquid chromatography with an electrochemical
      detector were applied to compare the characteristics of nicotine-evoked release
      of endogenous 3,4-dihydroxyphenylalanine (DOPA) from striata of conscious rats
      and those of the release of dopamine (DA). Dialysates were collected every 20 min
      3-8 h after the start of perfusion. Nicotine was perfused for 20 min through a
      probe. (+/-)-Nicotine (100-300 microM) constantly and repeatedly released DOPA
      and DA over a similar time course in a dose-dependent manner. The ratio of the
      DOPA and DA release evoked was approximately 1:3. The (+/-)-nicotine (200 microM)
      induced DOPA release was mecamylamine (500 microM)-sensitive, tetrodotoxin (100
      nM)-sensitive and Ca2+ (removal plus 12.5 mM Mg2+ addition)-dependent. The (+)
      isomer produced no DOPA release. These characteristics of DOPA release were
      almost the same as those of DA release. Furthermore, mecamylamine alone inhibited
      the basal release of DOPA but not of DA. Nicotine released stereoselectively
      endogenous DOPA via nicotinic acetylcholine receptors from striata of freely
      moving rats in a manner similar to transmitter DA. These acetylcholine receptors
      function tonically for the release of DOPA. These findings are further support
      for our proposal that DOPA is an endogenous neuroactive substance.

PMID- 1361444
TI  - Effects of ibutilide fumarate, a novel antiarrhythmic agent, and its enantiomers
      on isolated rabbit myocardium.
AB  - Ibutilide fumarate is currently in Phase II clinical trials for the treatment of
      life-threatening cardiac arrhythmias. The cardiovascular effects of ibutilide and
      its d- and l-stereoisomers, U82208E and U82209E were tested in an isolated rabbit
      myocardium system. In a series of repeated measures experiments, threshold,
      effective refractory period, force of contraction, conduction time and rate were
      measured at various pacing frequencies in isolated papillary muscles, ventricular
      muscle strips and right atria exposed to 10(-7), 10(-6) and 10(-5) M drug.
      Although there were occasional instances where one form had a greater or lesser
      effect on a given parameter, overall there was little pharmacological difference
      between the racemic mixture and its constituent forms. At the highest dose,
      effective refractory periods at 1 and 3 Hz increased by 18-32 ms, conduction
      times measured at 3 Hz increased by 27-30% and atrial rate decreased by 19-32%,
      while threshold and force of contraction were generally unaffected. In this study
      there were no clear cut pharmacologic differences between the three forms of this
      class III antiarrhythmic agent. Parallel studies to determine pA2 values of
      ibutilide and sotalol demonstrated that ibutilide possesses weak beta
      adrenoceptor blocking properties.

PMID- 1361445
TI  - Studies on the location of catecholamine receptors in canine sympathetic ganglia.
AB  - Receptors mediating catecholamine-induced inhibition were studied in cardiac
      ganglia of pentobarbital-anesthetized dogs. Using selective agonists and
      antagonists the presence of three receptor subtypes was verified: alpha 1- and
      alpha 2-adrenoceptors and dopamine D2 receptors. Activation of alpha 1
      adrenoceptors or dopamine D2 receptors reduced the response to preganglionic
      nerve stimulation but not to direct stimulation of the nicotinic acetylcholine
      receptors of the principal ganglion cells: response to both types of stimulation
      were reduced by activation of ganglionic alpha 2-adrenoceptors. These results
      suggested that two inhibitory systems were present in canine sympathetic ganglia
      and mediated the effects of exogenous catecholamines. One system involved alpha 1
      adrenoceptors and dopamine D2 receptors located proximal to the synapse of the
      pre- and postganglionic neurons and the other involved alpha 2-adrenoceptors
      located distal to the intraganglionic synapse.

PMID- 1361446
TI  - The adrenoceptor agonist, SDZ NVI 085, discriminates between alpha 1A- and alpha
      1B-adrenoceptor subtypes in vas deferens, kidney and aorta of the rat.
AB  - The potency of the alpha 1-adrenoceptor agonist (-)-(4aR, 10aR)-3,4,4a,5,10,10a
      hexahydro-6-methoxy-4-methyl-9-methylthio-2H -naphth [2,3-b]-1,4-oxazine (SDZ NVI
      085) was investigated both in isolated vas deferens and perfused kidney of the
      rat, two tissues with alpha 1A-adrenoceptor subtype characteristics, and in the
      rat thoracic aorta, in which the contribution of different alpha 1-adrenoceptor
      subtypes mediating contraction is controversial. In vas deferens and kidney, SDZ
      NVI 085 evoked smooth muscle contraction and vascular constriction and was of
      similar potency to L-phenylephrine. Contractions of vas deferens in response to (
      )-noradrenaline and SDZ NVI 085 were resistant to chloroethylclonidine treatment
      (3 x 10(-5) M), sensitive to (+/-)-isradipine (10(-8) M) and competitively
      antagonized by 5-methyl-urapidil (pA2 = 9.04 and 8.82, respectively). The
      potencies of a number of alpha 1A-/alpha 1B-adrenoceptor-discriminating
      antagonists to reverse renal vasoconstriction due to either (-)-noradrenaline or
      SDZ NVI 085, and their affinities in vas deferens correlated significantly with
      their pKi values at alpha 1A binding sites in rat cortex. In rat aorta, SDZ NVI
      085 up to 5 x 10(-4) M failed to evoke contraction. The affinities of subtype
      selective antagonists determined in aorta correlated significantly with the pKi
      values at alpha 1B binding sites but differed from pKi values at alpha 1A sites
      in rat cortex. Thus, the contractile alpha 1-adrenoceptor in rat aorta can be
      best characterized as B subtype. SDZ NVI 085 might be a selective alpha 1A
      adrenoceptor agonist and thus be used as a new tool either to detect (rat vas
      deferens and kidney) or exclude (rat aorta) a contribution of alpha 1A
      adrenoceptors functionally involved in smooth muscle contraction.

PMID- 1361448
TI  - Effect of human thyroid stimulating autoantibodies on the radioiodine uptake of
      the mouse thyroid gland.
AB  - Administration of sera from patients with active Graves' disease to nude mice
      bearing human thyroid xenografts provides the opportunity to compare directly the
      effects of TSAb on thyroid tissue of different species. The results presented in
      this paper, namely the fact that only one of 8 Graves' sera increased the RAIU of
      the nu/nu mouse thyroids modestly while all sera increased the RAIU in the
      transplanted human tissue considerable, clearly show a species specific effect of
      TSAb.

PMID- 1361447
TI  - The NMDA receptor antagonist MK-801 prevents imipramine-induced supersensitivity
      to quinpirole.
AB  - Chronic treatment with imipramine enhanced the locomotor stimulant response to
      quinpirole (0.3 mg/kg s.c.), a dopamine D2/D3 receptor agonist. Chronic, but not
      acute, blockade of the NMDA receptor with the non-competitive antagonist MK-801
      (0.3 mg/kg i.p.) prevented the imipramine-induced potentiation of the quinpirole
      effect. The results suggest that NMDA receptors play a role in the development of
      supersensitivity to dopamine receptor agonists produced by chronic antidepressant
      treatment.

PMID- 1361449
TI  - In vivo effects of TSH, TSH-receptor antibodies, and interferon-alpha-2b in
      xenografted human thyroid carcinoma.

PMID- 1361450
TI  - Evidence for the presence of a functional TSH-receptor in retroocular fibroblasts
      from patients with Graves' ophthalmopathy.

PMID- 1361451
TI  - Recombinant TSH-receptor for determination of TSH-receptor-antibodies.
AB  - We have expressed the complete coding sequence of the human TSH-R in eucaryotic
      cells. Limiting dilution enabled us to select two clones, JP09 and JP26, which
      have formed the basis of binding and bioassays respectively, for TSH-R
      antibodies. Results obtained in the binding assay correlated well with those
      obtained in the TRAK (Henning Berlin) assay, while the bioassay was at least as
      sensitive as measurements made with FRTL5 or human thyroid cells. These cell
      lines provide a reliable source of human TSH-R which will be useful in routine
      diagnosis.

PMID- 1361452
TI  - Measurement of stimulating TSH receptor antibodies in sera of patients with
      Graves' disease by a recombinant TSH receptor bioassay.

PMID- 1361453
TI  - Modulation of leukemic cell sensitivity to lymphokine-activated killer cytolysis:
      role of intercellular adhesion molecule-1.
AB  - The role of CD11/CD18 leukocyte adhesion molecules and their ligands in mediating
      non-major histocompatibility complex (MHC) restricted lymphocyte cytotoxicity is
      controversial. In order to examine the role of target cell intercellular adhesion
      molecule-1 (ICAM-1; CD54), a ligand of lymphocyte function-associated antigen
      (LFA-1) (CD11a/CD18), we exposed the human leukemia cell line, HL-60, to a
      variety of agents implicated in modulating ICAM-1 expression and/or sensitivity
      to lymphocyte cytolysis. Exposure of HL-60 cells to retinoic acid (RA),
      interferon (IFN)-alpha, IFN-beta, and IFN-gamma induced protection from
      lymphokine-activated killer (LAK) cytolysis. Only RA and IFN-gamma induced ICAM-1
      expression. Tumor necrosis factor and vitamin D3, which also induced ICAM-1
      expression, increased HL-60 sensitivity to LAK lysis. Granulocyte-macrophage
      colony-stimulating factor also increased sensitivity to LAK lysis; ICAM-1 was not
      induced. The state of cellular differentiation and expression of class I and II
      MHC antigens also did not correlate with sensitivity to LAK cytolysis. Exposure
      of untreated HL-60 cells and HL-60 cells expressing ICAM-1 to monoclonal antibody
      (mAb) versus ICAM-1 did not modulate LAK sensitivity. Exposure of LAK cells to
      mAb versus LFA-1 partially inhibited cytolysis; mAb versus CD18 inhibited
      cytolysis more completely. HL-60 cells were resistant to natural killer lysis;
      exposure to the various experimental agents did not alter sensitivity. We
      conclude that leukemic cell sensitivity to LAK cytolysis can be modulated by a
      variety of agents. Although our results suggest a role for leukocyte CD11/CD18
      adhesion molecules in LAK cytolysis, the poor correlation between ICAM-1
      expression and sensitivity to LAK lysis suggest that interactions other than LFA
      1/ICAM-1 conjugation may be more central to the processes involved.

PMID- 1361454
TI  - Adhesion receptors are differentially expressed on developing thymocytes and
      epithelium in human thymus.
AB  - The thymic microenvironment consists of a network of interrelated cells of
      epithelial, fibroblastic, endothelial, and hemopoietic origin. Within this
      environment, the development of specific T-lymphocyte subpopulations partially
      depends on the selective interaction of T-cell precursors with such cells. Human
      thymic epithelial cell strains, generated with a defective retroviral vector
      containing simian virus 40 (SV40) large T antigen and the neomycin resistance
      gene or by transfection with an SV40 plasmid defective in the origin of
      replication, provide useful tools for understanding the mechanisms contributing
      to the control of T-cell maturation. Because interepithelial, epithelial
      macrophage, and lymphocyte-epithelial cell interactions are important for
      thymocyte differentiation, the distribution of integrin and nonintegrin adhesion
      receptors on these cells and on developing thymocytes in vivo and in vitro has
      been examined in detail. Our results indicate that the transformed human thymic
      epithelial cell strains express the common very late antigen (VLA)-beta 1
      receptor and unique alpha chains VLA-2, VLA-3, and VLA-6. The cells are also
      positive for LFA-3 and ICAM-1 and weakly express beta 3, beta 4, and VNR alpha.
      They do not express the Leu-cellular adhesion molecules (CAM). This phenotypic
      profile on cultured thymic epithelium generally corresponds to the distribution
      of integrin and other receptor molecules on thymic epithelial cells in tissue
      sections. The majority of thymocytes also express the integrin VLA-beta 1 and 
      beta 2 chains as well as VLA-4, VLA-6, and LFA-1 alpha(L). Three-color flow
      cytometric analyses show differential levels of expression of these adhesion
      receptors on human thymocyte subsets. Taken together with the immunohistochemical
      localization of extracellular matrix molecules, these studies suggest that both
      the distribution of receptor-ligand pairs and the level of expression of adhesion
      molecules may influence T-cell development within the thymus.

PMID- 1361456
TI  - No genetic differences between affected and unaffected members of a German family
      with Leber's hereditary optic neuropathy (LHON) with respect to ten mtDNA point
      mutations associated with LHON.
AB  - In order to investigate possible synergistic influences of different mtDNA
      mutations on penetrance and severity of Leber's hereditary optic neuropathy
      (LHON), a large German LHON pedigree is characterized with respect to 10
      different mutations associated with LHON. All members of the family carry three
      different mtDNA mutations (at nucleotide 4,216, 11,778 and 13,708) in a
      homoplasmic form, regardless of whether or not they are clinically affected.
      Testing for another 7 mutations reveals negative results in all family members.
      Hence, the variable disease expression of the family members cannot be explained
      by varying combinations of LHON-associated mtDNA mutations.

PMID- 1361455
TI  - Functional characterization of mouse granulocytes and macrophages produced in
      vitro from bone marrow progenitors stimulated with interleukin 3 (IL-3) or
      granulocyte-macrophage colony-stimulating factor (GM-CSF).
AB  - Bone marrow from C3H/ouj mice was depleted to < 1% of CD11b+ granulocytes and
      macrophages using paramagnetic beads coated with sheep anti-rat antibodies. CD11b
      cells, enriched three- to fourfold in colony-forming cells, were stimulated in
      liquid culture with interleukin 3 (IL-3) or granulocyte-macrophage colony
      stimulating factor (GM-CSF). Cultures stimulated with IL-3 or GM-CSF increased
      cell numbers fourfold at 7 days, with the CD11b+ population increasing to 63% +/-
      9% (n = 5) with IL-3 or 96% +/- 1% (n = 4) cells with GM-CSF. Functional
      responsiveness of the granulocytes and macrophages was assessed by flow cytometry
      in an oxidative burst assay using dichlorofluorescein (DCF) and a quantitative
      phagocytosis assay using opsonized fluorescent beads. Granulocytes and
      macrophages, identified by light scatter characteristics and allophycocyanine
      staining of CD11b, were assayed simultaneously with granulocytes from fresh mouse
      bone marrow and peripheral blood. GM-CSF-generated CD11b+ cells had higher
      oxidative responses than similar populations produced in response to IL-3. The
      oxidative burst of these in vitro generated CD11b+ populations was similar to the
      equivalent fresh bone marrow population. Oxidative burst responses of peripheral
      blood phagocytic cells could not be adequately measured in this system.
      Peripheral blood CD11b+ cells were the most phagocytic, followed by GM-CSF
      stimulated CD11b+ cells; IL-3-stimulated and bone marrow CD11b+ cells were the
      least phagocytic. These data demonstrate that functional granulocytes can be
      produced in vitro using growth factors and that GM-CSF produces a more responsive
      cell than IL-3.

PMID- 1361457
TI  - POU-specific domain of Oct-2 factor confers 'octamer' motif DNA binding
      specificity on heterologous Antennapedia homeodomain.
AB  - The bipartite DNA binding domain of the POU family of transcription factors
      contains a 'POU-specific' domain unique to this class of factors and a 'POU
      homeodomain' homologous to other homeodomains. We compared DNA binding of the Oct
      2 factor POU domain and the Antennapedia (Antp) homeodomain with a chimeric Oct
      2/Antp protein in which the distantly related Antp homeodomain was substituted
      for the Oct-2 POU homeodomain. The Oct-2/Antp chimeric protein bound both the
      octamer and the Antp sites efficiently, indicating that DNA binding specificity
      is contributed by both components of the POU domain.

PMID- 1361458
TI  - Neuropeptide Y: a novel neuroendocrine peptide in the control of pituitary
      hormone secretion, and its relation to luteinizing hormone.
AB  - Evidence that establishes neuropeptide Y (NPY) as an important neuromessenger in
      the regulation of anterior pituitary hormone secretion is reviewed. In
      particular, NPY plays a critical role in stimulating the episodic, basal pattern
      of luteinizing hormone (LH) release, as well as the preovulatory surge of LH
      release in several species. The stimulatory effect of NPY on LH secretion is
      dependent upon the presence of gonadal hormones and involves amplification of the
      response of other interacting stimulatory signals. NPY acts at the level of the
      median eminence to excite the release of LH-releasing hormone (LHRH) via a
      mechanism that leads to the mobilization of intracellular Ca2+. These stimulatory
      LHRH responses are mediated by Y1NPY receptors. Moreover, NPY activates
      postsynaptic messenger pathways that complement and reinforce those affected by
      norepinephrine, which is another major neuroregulator of LHRH secretion and which
      is released as a cotransmitter with NPY in the median eminence. Additionally, NPY
      is released into the hypophyseal portal blood for transportation to the anterior
      pituitary where it enhances the release of LH in response to LHRH. This
      facilitatory, modulating effect at the pituitary level involves an allosteric
      increase in LHRH binding to its receptor leading to augmented influx of Ca2+ from
      the extracellular space. There is evidence that gonadal steroids regulate NPY
      neurosecretion in a site-specific manner, and that alterations in NPY secretion
      may occur in part via a direct action of the steroids on NPY neurons in the
      brainstem and hypothalamus and in part through an indirect effect involving
      removal of the inhibitory influence of endogenous opioid peptides. These findings
      are integrated into an overall hypothesis for induction of the preovulatory LH
      surge on proestrus requiring an interplay between NPY and other neuronal
      networks. In aged male rats, due to the inability of hypothalamic NPY neurons to
      respond appropriately to the trophic effects of androgens, NPY neurosecretion is
      diminished. Further, a review of the literature reveals that NPY may modulate the
      secretion of other pituitary hormones through a similar combination of
      hypothalamic and pituitary actions.

PMID- 1361459
TI  - Unexplained infertility: a review of diagnosis, prognosis, treatment efficacy and
      management.
AB  - The dilemma of unexplained infertility posed by Southam in 1960 remains today:
      despite advances in the diagnostic assessment of infertility, many couples still
      have no explanation for their infertility. Even the most sophisticated evaluation
      of semen, ovulation and genital tract competence cannot reveal all of the
      possible defects in the complex process leading to conception. Because it arises
      from these shortcomings in our knowledge of fertilization and from our inability
      to utilize all of the current knowledge, unexplained infertility is a challenge
      for both biological and clinical research. This paper attempts to summarize some
      clinical issues in the management of unexplained infertility: the prevalence of
      the disorder, problems in the definition and possible explanations for the
      existence of this diagnostic category. It reviews outcome-based clinical
      publications as a guide to decision-making on what diagnostic tests to use,
      provides a summary of the untreated prognosis and evaluates study results that
      may serve as a basis for treatment decisions in this puzzling diagnostic category
      of infertility.

PMID- 1361461
TI  - A trial of labor after cesarean section in patients with or without a prior
      vaginal delivery.
AB  - OBJECTIVE: To determine the outcome of labor in women with a previous cesarean
      section, with or without prior vaginal delivery. METHOD: Records were reviewed
      for 1065 women with a previous cesarean section at 'Virgen Macarena' Hospital who
      were attended for a subsequent labor. RESULTS: Chi-squared tests demonstrated
      that women with previous vaginal delivery (n = 346) had a significantly higher
      rate of vaginal delivery after a trial of labor (95.24%) than those without
      previous vaginal delivery (n = 719) (82.95%). All the ruptures of uterine scar (n
      = 4) were found in women without previous vaginal delivery. CONCLUSION: It
      appears that a cesarean section in a multiparous woman is not a determinant fact
      in her reproductive history and the risk of rupture of uterine scar did not
      appear to be present.

PMID- 1361460
TI  - Maternal weight, weight gain during pregnancy and pregnancy outcome.
AB  - OBJECTIVE: To evaluate the effects of abnormal maternal weight or weight gain on
      pregnancy outcome. METHOD: Records for 191 mothers with abnormal prepregnancy
      weight (> or = 20%) above, or under, ideal body weight for height) or weight gain
      > or = 20 kg, or < or = 5 kg during pregnancy were reviewed. The control group
      consisted of 166 mothers with normal prepregnancy weight and normal weight gain
      during pregnancy. Data on mothers and their infants were analyzed by one-way
      analysis of variance. RESULTS: Obese women and mothers with excessive weight gain
      during pregnancy had an increased incidence of induced labor (P < or = 0.05) and
      tendency for emergency cesarean sections during the delivery. Obese women had
      more large-for-date babies than controls (P < or = 0.05). Weight gain < or = 5 kg
      during pregnancy was most common in slightly obese women and did not carry any
      special obstetric or neonatal risk. Underweight women had a significant risk for
      delivering a small-for-data baby. CONCLUSION: Obese women and women with
      excessive weight gain during pregnancy need special follow-up and counseling
      during pregnancy and delivery. Underweight women may need prepregnancy
      nutritional counseling to guarantee normal fetal growth. In developed countries
      suboptimal weight gain (< or = 5 kg) during pregnancy seems not to need any
      medical intervention.

PMID- 1361462
TI  - Potential relationship between dengue fever and neural tube defects in a northern
      district of India.
AB  - A sudden increase in number of births of newborns with neural tube defects (NTD)
      was observed from June, 1989 to September, 1989 in Medical College and Hospital,
      Rohtak and various other government and private hospitals of the district of
      Rohtak. Out of a total 4785 deliveries whose records were collected, there were
      87 newborns with NTD with an incidence of 18.18/1000 births which was three times
      higher than the previous incidence of 6.8/1000 births in the preceding 4 years.
      There was an epidemic of dengue fever in this area from September, 1988 to
      December, 1988 affecting almost one member from each family. This coincided with
      the period of their first trimester. Of these, 18 patients suffered clinically
      from dengue fever, 21 patients had positive dengue fever history in their family
      members, 21 patients had positive history in their neighbors. The cluster of NTD
      appears to be due to dengue virus infection.

PMID- 1361463
TI  - Use of low molecular weight heparin for prophylaxis and treatment of
      thromboembolism in pregnancy.
AB  - Low molecular weight heparin (LMWH) preserves the antithrombotic action but not
      the anticoagulant activity of heparin. LMWH is safe, does not cross the placenta
      and is administered as a single daily injection. We report our experience with 6
      pregnant women given LMWH for treatment or prophylaxis of thromboembolism. The
      drug was successfully given to 5 women for periods of 6 weeks--6 months and no
      thromboembolic complications occurred during pregnancy or pueperium. There were
      no hemorrhagic complications and no excessive bleeding was observed during
      delivery. The sixth patient relapsed after 6 weeks of therapy. This patient also
      showed resistance to standard heparin administered intravenously at a very high
      dose. LMWH should be considered an alternative to standard heparin in pregnant
      women requiring antithrombotic prophylaxis and therapy.

PMID- 1361464
TI  - Ovarian function after conservational ovarian surgery: a long-term follow-up
      study.
AB  - OBJECTIVE: To determine the long-term effects of conservational ovarian surgery
      on subsequent ovarian function. METHOD: Medical, surgical and menstrual records
      of 87 reproductive age women who have undergone pelvic surgery for indications
      including endometriosis, infertility, and pelvic pain between June 1982 and June
      1989 were retrospectively reviewed. RESULTS: Sixty-seven patients had ovarian
      surgery during their procedure; 26 ovarian cystectomies (OC), 19 partial ovarian
      resections (OR) and 22 ovariolyses (OL). Twenty patients had no ovarian surgery
      (NOS). The mean follow-up period was comparable in all groups (OL 32 +/- 15
      months, OR 34 +/- 26 months, OC 41 +/- 30 months and NOS 37 +/- 21 months). The
      mean time to onset of the first postoperative menses was not significantly
      different among the four groups (OL 24 +/- 7 days, OR 24 +/- 13 days, OC 29 +/-
      26 days and NOS 22 +/- 6 days). The cumulative conception rates were not
      significantly different (OL 23%, OR 37%, OC 19% and NOS 25%). Menstrual
      disturbances, defined as perceived deviations from preoperative patterns, did not
      appear to be related to the type or extent of ovarian surgery and occurred in
      comparable frequencies among patients with or without ovarian surgery (OL 23%, OR
      37%, OC 23% and NOS 20%). In the majority of cases, menstrual disturbances
      occurred either in the early postoperative months and were self-limited, or much
      later in which case they were related to recurrent endometriosis. Premature
      ovarian failure has so far occurred in one patient suggesting an incidence
      comparable to that in the general population. CONCLUSIONS: It is concluded that
      in this group of patients, conservational ovarian surgery had no significant
      effects on ovulatory and menstrual function over a prolonged follow-up period.

PMID- 1361465
TI  - Scanning electron microscopy of endometriotic lesions in the pelvic peritoneum
      and the histogenesis of endometriosis.
AB  - OBJECTIVE: To determine whether the epithelium of an endometriotic lesion has
      eutopic endometrial glandular epithelium morphology or not for the histogenesis
      of endometriosis. METHOD: Scanning electron microscopy (SEM) of the endometrium
      was done for 25 cases. Histologically proven endometriotic lesions of 10 of these
      25 cases were processed for SEM. Peroneum samples of another 15 cases without
      histological endometriosis were also studied. RESULT: Three of 10 cases with
      histologically proven endometriotic lesions revealed endometrium-like morphology
      by SEM, whereas normal appearing peritoneum without histological endometriosis in
      15 cases showed no endometrium-like structures by SEM. CONCLUSION: Although
      abovementioned results did not support retrograde menstruation and implantation,
      they suggested a possibility of derivation from the endometrium.

PMID- 1361466
TI  - The feasibility of suppressing ovarian activity following the end of amenorrhoea
      by increasing the frequency of suckling.
AB  - OBJECTIVE: To determine the feasibility of suppressing ovarian activity by
      increasing the frequency of suckling episodes. METHOD: Prospective study was
      carried out with 19 exclusively breastfeeding volunteers. Ten subjects
      (experimental group) increased the suckling episodes by minimum 50% per day from
      the beginning of the first postpartum menses. Nine controls continued
      breastfeeding as before. Estradiol, progesterone, LH, FSH and prolactin were
      measured in blood samples, drawn twice a week up to the second postpartum menses
      or for 60 days, by RIA. Student's t-test was employed. RESULT: The higher
      suckling frequency prevented ovulation in 7 of 10 cases examined according to the
      plasma progesterone concentration (< 9.5 nmol/l). Significantly higher average
      prolactin value could also be found in the experimental group (1038 (527)
      munits/l vs. 518 (245) munits/l; P < 0.05). CONCLUSION: Results suggest that an
      earlier initiation of the increase in breastfeeding frequency may delay the
      resumption of ovulation. Frequent, full time lactation may reduce the risk of
      pregnancy.

PMID- 1361467
TI  - Prenatal diagnosis of recurrent Meckel syndrome.
AB  - We report a rare case of Meckel-Gruber syndrome in a woman who had three affected
      offsprings in the past with similar condition. Ante-natal ultrasonographic
      diagnosis and management are presented.

PMID- 1361468
TI  - Surgical emergency in the fetus as indication for cesarean section.

PMID- 1361469
TI  - A two-step approach to the treatment of invasive vulvar cancer in pregnancy.

PMID- 1361470
TI  - Z-sampler for outpatient diagnosis of endometrial sampling.

PMID- 1361471
TI  - Munchausen syndrome presenting as uncontrolled menorrhagia.

PMID- 1361472
TI  - Fetal macrosomia. ACOG Technical Bulletin Number 159--September 1991.
AB  - When macrosomia exists, shoulder dystocia is a primary obstetric concern. Current
      methods for estimating birth weight prior to delivery are imprecise, and
      macrosomia often cannot be predicted. Certain conditions or combinations of
      conditions should increase the index of suspicion for shoulder dystocia. When
      these conditions are identified, consideration should be given to the management
      of potential shoulder dystocia. Despite due care and appropriate clinical
      judgment, however, injury during the birth process cannot always be prevented.

PMID- 1361473
TI  - Ethical dimensions of informed consent. ACOG Committee Opinion: Committee on
      Ethics. Number 108--May 1992.

PMID- 1361476
TI  - Evidence for orthologous seed weight genes in cowpea and mung bean based on RFLP
      mapping.
AB  - A well saturated genomic map is a necessity for a breeding program based on
      marker assisted selection. To this end, we are developing genomic maps for cowpea
      (Vigna unguiculata 2N = 22) and mung bean (Vigna radiata 2N = 22) based on
      restriction fragment length polymorphism (RFLP) markers. Using these maps, we
      have located major quantitative trait loci (QTLs) for seed weight in both
      species. Two unlinked genomic regions in cowpea contained QTLs accounting for
      52.7% of the variation for seed weight. In mung bean there were four unlinked
      genomic regions accounting for 49.7% of the variation for seed weight. In both
      cowpea and mung bean the genomic region with the greatest effect on seed weight
      spanned the same RFLP markers in the same linkage order. This suggests that the
      QTLs in this genomic region have remained conserved through evolution. This
      inference is supported by the observation that a significant interaction (i.e.,
      epistasis) was detected between the QTL(s) in the conserved region and an
      unlinked RFLP marker locus in both species.

PMID- 1361474
TI  - Ectopic expression of the Drosophila homeotic gene proboscipedia under
      Antennapedia P1 control causes dominant thoracic defects.
AB  - A deletion mutation in the Antennapedia Complex of Drosophila melanogaster,
      Df(3R)SCBXL2, induces both dominant and recessive loss-of-function phenotypes.
      The deletion is associated with diminished function of proboscipedia (pb), a
      homeotic gene required for mouthparts formation. Df(3R)SCBXL2 also has associated
      dominant thoracic defects related to diminished expression of the homeotic
      Antennapedia (Antp) gene copy on the homologous chromosome. This is shown to be a
      consequence of ectopic pb expression in the thorax. Newly juxtaposed Antp
      sequences provide the pb gene on the deletion bearing chromosome with a second
      promoter, Antp P1, in addition to its own. Ectopic pb protein expression occurs
      under Antp P1 control, by alternate splicing, and results in diminished
      accumulation of Antp protein in the imaginal disc cells where Antp P1 is normally
      expressed. The analysis of this mutant chromosome thus demonstrates that pb
      protein is capable of participating in the negative regulation of a more
      posteriorly expressed homeotic gene, as well as serving a homeotic "selector"
      function in the head.

PMID- 1361475
TI  - Polymorphism and divergence in the Mst26A male accessory gland gene region in
      Drosophila.
AB  - Drosophila males, like males of most other insects, transfer a group of specific
      proteins to the females during mating. These proteins are produced primarily in
      the accessory gland and are likely to influence the female's reproduction. The
      results of studies of DNA sequence polymorphism and divergence in two genes
      coding for male accessory gland proteins of Drosophila are reported here. The
      Mst26Aa and Mst26Ab transcription units are tandemly arranged in a approximately
      1.6-kb segment in Drosophila sechellia, Drosophila mauritiana and Drosophila
      simulans as they were reported to be in Drosophila melanogaster. The DNA
      sequences of 10 alleles from D. melanogaster and one allele each from the three
      sibling species reveals a high degree of amino acid replacement variation. A
      substantial part of the variation is due to insertion/deletion differences.
      Possible functional significance of these amino acid sequence changes is
      discussed. Statistical analyses based on the neutral theory of molecular
      evolution show that the distribution of polymorphism over the 1.6-kb region is
      inconsistent with the pattern of divergence between the species. The amount of 4
      cutter restriction map polymorphism in a larger sample of 75 alleles from the
      same D. melanogaster population is similar to that obtained from the DNA sequence
      of the 10 alleles (a pairwise average of 0.007 difference per site). The 6-cutter
      restriction map survey of a 18-kb region containing the Mst26A genes indicates
      that polymorphism in the region flanking these genes maybe higher. The failure of
      polymorphisms and divergence in the Mst26A region to conform to the expectations
      of a simple mutation-drift-equilibrium model indicates that selection in or near
      this region has played a role in the history of these genes.

PMID- 1361477
TI  - [Genetic differentiation of the inhabitants of Mongolia. Geographic distribution
      of mitochondrial DNA RFLPs and mitotypes in the inhabitants of Mongolia and a
      population assessment of the mutation rate in the mitochondrial genome].
AB  - The geographical distribution of the Asian specific deletion--insertion
      polymorphisms and or the RFLP's in the V noncoding region and the D-loop and of
      the mitotypes was analysed in Mongolia. The frequencies of the mtDNA markers
      demonstrated homogeneity of 18 local groups in Mongolia. The geographical
      distribution of the mitotypes showed the existence of two ancestral maternal
      lineages in mongols. There was no significant difference in the average FST
      values between mitochondrial gene flow and the nuclear gene flow of the Mongolian
      population. The equality of FST values permit to calculate the mutation rate for
      the human mtDNA--6.10(-9) per nucleotide per year. The data reveals the Mongolian
      population is in the equilibrium.

PMID- 1361478
TI  - HER-2/neu expression: a major prognostic factor in endometrial cancer.
AB  - The HER-2/neu oncogene encodes for a specific cell-surface glycoprotein similar
      to the human growth factor receptor. An analysis of 247 patients with endometrial
      cancer treated between 1979 and 1983 was performed using an immunoperoxidase
      technique on paraffin-embedded tissue samples to detect HER-2/neu overexpression.
      Specimens were graded blindly with regard to HER-2/neu staining intensity.
      Overexpression of HER-2/neu was identified as strong in 37 patients (15%), mild
      in 144 (58%), and none in 66 (27%). The 5-year progression-free survival was 56%
      for the strong, 83% for the mild, and 95% for the nonstaining groups. The strong
      (P < 0.0001) and the mild (P = 0.028) staining groups were distinct from the
      nonstaining group in predicting progression-free survival. Likewise, strong
      overexpression was associated with a poor (51%) overall survival (P < 0.0001).
      Multivariate analysis revealed that intense overexpression had independent
      significance in predicting progression-free (P = 0.0003) and overall survival (P
      < 0.0001). In stage I patients (203), the 5-year progression-free survival was
      62% for the strong and 97% for the nonstaining groups (P = 0.0007). This retained
      independent significance when subjected to multivariate analysis (P = 0.0017).
      Other significant stage I prognostic factors in multivariate analysis included
      DNA ploidy, histologic subtype, and histologic grade but not depth of invasion.

PMID- 1361479
TI  - Proliferating cell nuclear antigen in epithelial ovarian cancer: relation to
      results at second-look laparotomy and survival.
AB  - We determined the proliferative index (PI) of 92 previously untreated advanced
      epithelial ovarian cancers using PCNA/cyclin immunostaining and image analysis
      quantitation. In this retrospective study, there was a relationship between tumor
      PI and 5-year survival. For patients with a tumor PI greater than the median, the
      estimated 5-year survival was 44%; for patients with a tumor PI below the median,
      the estimated 5-year survival was 15% (P = 0.003). This may partly reflect
      sensitivity to chemotherapy, as those patients with more rapidly proliferating
      tumors were more likely to achieve a pathologic complete response to platinum
      based therapy.

PMID- 1361480
TI  - C-erbB-2-oncogene expression in breast carcinoma: analysis by S1 nuclease
      protection assay and immunohistochemistry in relation to clinical parameters.
AB  - The c-erbB-2 mRNA was detected by the S1 nuclease protection assay and Northern
      blotting in breast cancer tissues. In contrast to the Northern blot analysis
      which has been used in all recent publications concerning c-erbB-2 expression on
      the level of RNA, the S1-nuclease protection assay has distinct advantages with
      respect to sensitivity, reproducibility, and handling of radioactive probes. We
      compared the expression of c-erbB-2 in 120 breast carcinomas which were operated
      in the years 1989-1990 on the level of the mRNA (S1 nuclease protection assay)
      and the protein (immunohistochemistry), respectively. In general, results
      obtained with both methods were in good agreement. Only minor differences in
      classification were observed with 18 samples, all of them belonging to either the
      moderate or the weak c-erbB-2 expression phenotype. In addition, the level of c
      erbB-2-protein was investigated by immunohistochemistry in 271 breast carcinomas
      which were operated in the years 1984-1987. Comparison of the level of c-erbB-2
      expression with the patient history indicates that patients whose tumors had
      already metastasized to the axillary nodes showed a reduced overall and disease
      free survival in the group with pronounced expression of the c-erbB-2 protein.
      Thus the strong expression of c-erbB-2 oncogene in primary breast cancers appears
      to be an additional and particular prognostic factor in lymph node positive
      patients.

PMID- 1361481
TI  - [Physiology of Doppler blood flow in maternal blood vessels in pregnancy].

PMID- 1361482
TI  - The complexities of proliferating cell nuclear antigen.

PMID- 1361483
TI  - 2nd International Pediatric Airway Symposium. Pittsburgh, Pennsylvania, November
      1991.

PMID- 1361484
TI  - Effects of dopaminergic agents on cardiac and renal function in normal man and in
      patients with congestive heart failure.
AB  - Dopamine is an effective drug in the management of acute congestive heart
      failure. Its beneficial action is due to both cardiovascular--peripheral
      vasodilation and positive inotropy--and renal effects. Dopexamine is one of the
      newer dopamine agonists. Like dopamine, however, it can only be administered
      intravenously, and its value in the chronic treatment of congestive heart failure
      is limited. For this reason, dopamine analogs were developed with oral
      bioavailability, including levodopa, fenoldopam and biopamine. Although both
      levodopa and fenoldopam have shown beneficial hemodynamic effects, these agents
      cannot be recommended for general use in patients with congestive heart failure.
      Levodopa frequently causes side effects, especially nausea, and fenoldopam
      induces an increase in neurohumoral activity, which limits its long-term
      efficacy. Ibopamine has vasodilatory, mild inotropic and diuretic properties and
      it lowers plasma norepinephrine levels. Since ibopamine is usually well
      tolerated, it appears to have the most interesting profile of these oral
      dopaminergic agents.

PMID- 1361485
TI  - 1992 Association of University Radiologists Research Symposium. Chicago,
      Illinois, April 21-22, 1992.

PMID- 1361486
TI  - Matlystatins, new inhibitors of typeIV collagenases from Actinomadura
      atramentaria. II. Biological activities.
AB  - Matlystatin A, the main component of matlystatins, inhibits 92 kDa and 72 kDa
      typeIV collagenases with IC50 values of 0.3 microM and 0.56 microM, respectively,
      while 7- to 11-fold greater concentrations are required to inhibit thermolysin
      and aminopeptidase M. The inhibition is reversible and competitive with respect
      to gelatin. It inhibits the invasion of basement membrane Matrigel by human
      fibrosarcoma HT1080 dose-dependently with an IC50 value of 21.6 microM.

PMID- 1361487
TI  - Pyrizinostatin: a new inhibitor of pyroglutamyl peptidase.

PMID- 1361488
TI  - Mutational analysis of centrin: an EF-hand protein associated with three distinct
      contractile fibers in the basal body apparatus of Chlamydomonas.
AB  - Centrin, a 20-kD phosphoprotein with four calcium-binding EF-hands, is present in
      the centrosome/basal body apparatus of the green alga Chlamydomonas reinhardtii
      in three distinct locations: the nucleus-basal body connectors, the distal
      striated fibers, and the flagellar transition regions. In each location, centrin
      is found in fibrous structures that display calcium-mediated contraction. The
      mutant vfl2 has structural defects at all of these locations and is defective for
      basal body localization and/or segregation. We show that the vfl2 mutation is a G
      to-A transition in the centrin structural gene which converts a glutamic acid to
      a lysine at position 101, the first amino acid of the E-helix of the protein's
      third EF-hand. This proves that centrin is required to construct the nucleus
      basal body connectors, the distal striated fibers, and the flagellar transition
      regions, and it demonstrates the importance of amino acid 101 to normal centrin
      function. Based on immunofluorescence analysis using anti-centrin antibodies, it
      appears that vfl2 centrin is capable of binding to the basal body but is
      incapable of polymerizing into filamentous structures. 19 phenotypic revertants
      of vfl2 were isolated, and 10 of them, each of which had undergone further
      mutation at codon 101, were examined in detail. At the DNA level, 1 of the 10 was
      wild type, and the other 9 were pseudorevertants encoding centrins with the amino
      acids asparagine, threonine, methionine, or isoleucine at position 101. No
      ultrastructure defects were apparent in the revertants with asparagine or
      threonine at position 101, but in those with methionine or isoleucine at position
      101, the distal striated fibers were found to be incomplete, indicating that
      different amino acid substitutions at position 101 can differentially affect the
      assembly of the three distinct centrin-containing fibrous structures associated
      with the Chlamydomonas centrosome.

PMID- 1361489
TI  - Activin A-induced differentiation in K562 cells is associated with a transient
      hypophosphorylation of RB protein and the concomitant block of cell cycle at G1
      phase.
AB  - The human erythroleukemic cell line, K562, can be induced to differentiate by the
      addition of activin A, a newly purified protein belonging to the TGF-beta 1
      family. The present studies used flow cytometric cell cycle analysis, indirect
      immunofluorescence staining of the proliferating cell nuclear antigen (PCNA), and
      thymidine incorporation assay of cell proliferation to study the effects of
      activin A on the cell cycle during differentiation in K562 cells. Activin A
      treated K562 cells were found to undergo a transient block in cell cycle,
      temporarily halting progression from G1 to S phase. The latter can be observed
      after approximately 24 hr of incubation with activin A and then disappears after
      this early stage of induction of differentiation. Cell cycle kinetics analysis
      using synchronized K562 cells also confirms that in the presence of activin A,
      K562 cells progress normally through various phases of cell cycle, except that
      there is prolongation of the G1 phase between 10 to 24 hr of culture.
      Furthermore, this transient arrest in G1 is correlated with dephosphorylation of
      a nucleoprotein, the RB gene product, which occurs within 9-24 hr of incubation
      with activin A; and phosphorylation of RB protein then develops afterward. In
      addition, these cell cycle-related events are observed to occur earlier than the
      accumulation of hemoglobins in K562 cells. It is concluded that transient
      dephosphorylation of RB protein and prolongation of G1 phase of cell cycle
      precede and accompany erythroid differentiation caused by activin A and chemical
      inducers, thus constituting part of the mechanism for induction of
      differentiation in the erythroleukemia cells.

PMID- 1361490
TI  - Restriction fragment length polymorphism analysis of HLA-DR- and DQ-linked
      alleles in multiple sclerosis in Spain.
AB  - HLA-DR allele subtypes in multiple sclerosis (MS) individuals in Spain were
      determined by restriction fragment length polymorphism (RFLP) analysis. The well
      established association of DRw15, DQw6, Dw2 alleles and MS susceptibility was
      confirmed. The strength of its association, however, was relatively weak in our
      MS population and no involvement with any other DR allele was observed. DQw6
      increase correlated with the elevation of the involved DR2 subtype. The
      hypothesis that MS-associated susceptibility genes may be more closely associated
      with the DQ than the DR region was not supported by our findings which, on the
      other hand, could be in concordance with the concept that multiple genes
      contribute to MS susceptibility.

PMID- 1361491
TI  - Detection of a new mutation in the beta-myosin heavy chain gene in an individual
      with hypertrophic cardiomyopathy.
AB  - Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant disease
      affecting primarily the myocardium. The gene responsible for FHCM has been
      localized to chromosome 14 in some families and several mutations have been
      described in the beta-myosin heavy chain (beta MHC), a candidate gene for the
      disease. We recently identified a family with HCM in whom we did not detect any
      of the known mutations in the beta MHC gene (the alpha/beta MHC hybrid gene and
      the missense mutation in exons 13 and 9). However, we did observe a novel 9.5-kb
      BamHI restriction fragment length polymorphism detected by a beta MHC probe on
      Southern blots of DNA from the proband of this family. Similarly, a novel 3.8-kb
      TaqI polymorphism and a novel 4.3-kb HindIII polymorphism were detected on
      Southern blots of DNA from the same proband. Polymerase chain reaction (PCR) was
      used to amplify the segment of the beta MHC that was detected by pSC14 probe. PCR
      amplification of the distal 3'-end of the beta MHC gene yielded an additional
      product in the DNA template from the proband which was subsequently cloned and
      sequenced. The sequence analysis showed a 2.4-kb nucleotide deletion involving
      one allele of the beta MHC gene. The deletion includes part of the intron 39,
      exon 40 including the 3'-untranslated region and the polyadenylation signal, and
      part of the beta-alpha MHC intergenic region. This deletion was inherited in
      Mendelian fashion in an additional three members of this small family of which
      only the proband has developed clinically diagnosed HCM at a very late onset (age
      59 yr), the other three family members are younger and have not developed the
      disease at the ages of 10, 32, and 33 yr.

PMID- 1361492
TI  - Beta cell expression of endogenous xenotropic retrovirus distinguishes diabetes
      susceptible NOD/Lt from resistant NON/Lt mice.
AB  - Endogeneous retroviral expression in beta cells is a feature of prediabetes in
      nonobese diabetic (NOD) mice. The purpose of this study was to characterize the
      class-specific pattern of retroviral gene expression in NOD/Lt beta cells versus
      a related, but diabetes-resistant strain, NON/Lt. Electron microscopic comparison
      of beta cells from both strains indicated low constitutive expression of the
      intracisternal type A (IAP) retroviral class. However, NOD beta cells, in
      contrast to NON beta cells, expressed an additional intracisternal retroviral
      form resembling a type C particle. Antibodies against both IAP and type C were
      detected in NOD, with the humoral response to type C, but not IAP, preceding
      decline in beta cell function. RNA was extracted from freshly isolated islets
      from NOD and NON males. Comparative Northern blot analysis of total type C
      retroviral gene expression using a gag-pol DNA probe corroborated expression of
      endogenous type C proviruses in both NOD and NON islet cells and thymus. Use of
      class-specific retroviral probes identified the class of expressed endogenous
      retrovirus distinguishing the two inbred strains. The single ecotropic provirus
      present in both the NOD and NON genome (Emv-30) was not expressed in islets or
      thymus of either strain. Comparison of endogenous xenotropic provirus content by
      Southern blot analysis revealed two unique xenotropic loci (Xmv-65, -66) in NOD;
      8.4 and 3.0 kb xenotropic envelope (env) RNA transcripts were detected in NOD,
      but not NON islets and thymus. NON contained three xenotropic loci common to
      other inbred strains (Xmv-21, -25, and -28). Both strains were partially
      characterized for content of recombinant (polytropic and modified polytropic)
      proviruses. IAP RNA expression was common to both NOD and NON islets and hence
      could not be specifically associated with the unique intracisternal type C
      particle found in NOD, but not NON beta cells. In conclusion, this study shows
      that expression of xenotropic type C but not IAP distinguishes retroviral
      activity in NOD/Lt versus NON/Lt beta cells. The potential pathogenic role of
      retroviral gene expression in NOD beta cells is discussed.

PMID- 1361493
TI  - Mesangial cell immune injury. Hemodynamic role of leukocyte- and platelet-derived
      eicosanoids.
AB  - The role of leukocytes and platelets and of leukocyte- and platelet-derived
      eicosanoids in mediating acute changes in renal and glomerular hemodynamics was
      assessed in a model of antibody-induced mesangial cell injury in the rat. After a
      single intravenous injection (6 mg/kg) of the monoclonal antibody (ER4) against
      the mesangial cell membrane antigen Thy 1, significant decrements in glomerular
      filtration rate (GFR) and renal blood flow (RBF) were observed at 1 h, and were
      associated with increments in glomerular LC (+) leukocyte counts and in the
      synthesis of thromboxane (Tx)B2, leukotriene (LT)B4, and 12
      hydroxyeicosatetraenoic acid (HETE). In rats with immune leukopenia, the rise in
      glomerular LC (+) leukocytes and in eicosanoid synthesis were abolished and the
      fall in GFR and RBF after administration of ER4 were completely ameliorated.
      Likewise, pretreatment of rats with both a thromboxane synthase and a 5
      lipoxygenase inhibitor also blocked the fall in GFR and RBF and the rise in
      glomerular synthesis of TxB2 and LTB4 produced by ER4 without changing glomerular
      LC (+) leukocyte counts. Selective inhibition of thromboxane or 5-lipoxygenase
      alone only partially ameliorated the decrements in GFR and RBF produced by ER4.
      In animals with immune thrombocytopenia, the elevated glomerular synthesis of 12
      HETE and fall in RBF but not GFR was ameliorated after administration of ER4. The
      ER4 antibody-induced fall in GFR was mainly caused by a marked decrement in the
      ultrafiltration coefficient, Kf, which was dependent on TxA2 and 5-lipoxygenase
      products, since pretreatment of animals with a thromboxane receptor antagonist or
      with a 5-lipoxygenase inhibitor partially ameliorated this decrement. Structural
      changes such as infiltration of glomerular capillaries by leukocytes and
      endothelial cell damage may also have accounted for the fall in Kf. These
      observations indicate that in antibody-mediated mesangial cell injury,
      infiltrating leukocytes and platelets mediate the changes in renal hemodynamics
      via synthesis of thromboxane and arachidonate 5-lipoxygenation products.

PMID- 1361494
TI  - Rat glomerular mesangial cells synthesize basic fibroblast growth factor.
      Release, upregulated synthesis, and mitogenicity in mesangial proliferative
      glomerulonephritis.
AB  - Mesangial injury and cell proliferation are frequent findings in various
      glomerular diseases in man. Previous studies have demonstrated that basic
      fibroblast growth factor (bFGF) is a potent mesangial cell mitogen in vitro. To
      further elucidate the role of bFGF in rat mesangial cell (RMC) proliferation, we
      examined whether RMC synthesize bFGF in vitro and whether bFGF is involved in
      mesangial proliferation in vivo. Cultured RMC expressed bFGF protein (23, 21.5,
      and 18 kD forms) and bFGF mRNA, and released biologically active bFGF into the
      culture medium after antibody- and complement-mediated injury. Normal rat
      glomeruli in vivo contained no detectable bFGF mRNA, but bFGF protein (23 and
      21.5 kD) could be demonstrated, which immunolocalized to the mesangium.
      Glomerular bFGF decreased markedly during the acute phase of glomerulonephritis
      induced by anti-Thy 1.1 antibody, compatible with mesangial bFGF release after
      complement-mediated mesangiolysis. During the subsequent mesangial proliferative
      phase, glomerular bFGF protein and mRNA increased above normal. Intrarenal
      infusion of heparin did not affect the bFGF immunostaining of glomeruli at this
      stage, indicating a predominantly intracellular localization of the bFGF. The
      capability of bFGF to mediate proliferation in the anti-Thy 1.1 model was further
      supported by experiments in which intravenous bFGF given 24 h after a
      subnephritogenic dose of anti-Thy 1.1 antibody led to a 4.9- to 5.1-fold increase
      in glomerular cell proliferation (with > 60% of the cells identified as mesangial
      cells by double immunolabeling). No such increase was observed in normal rats
      injected with bFGF. These data show that mesangial cells produce and release bFGF
      after injury and that bFGF is mitogenic for injured mesangial cells in vivo.
      Release of mesangial cell bFGF thus may be an important mechanism involved in the
      initiation of mesangial cell proliferation in vivo.

PMID- 1361496
TI  - Monoaminergic systems in the brainstem and spinal cord of the turtle Pseudemys
      scripta elegans as revealed by antibodies against serotonin and tyrosine
      hydroxylase.
AB  - With the aim of gaining more insight into the monoaminergic regulation of spinal
      motor systems in the turtle, we have studied the distribution of 5-HT (5-HTir)
      and tyrosine hydroxylase immunoreactivity (THir) in the brainstem and spinal cord
      of Pseudemys scripta elegans. 5-HTir cell bodies were located in the midline in
      nucleus raphe inferior, nucleus raphe superior, and laterally in nuclei
      reticularis superior and inferior and nucleus reticularis isthmi. THir cell
      bodies were located in the commissural nucleus, nucleus tractus solitarii, the
      locus coeruleus-subcoeruleus complex, nuclei reticularis superior and inferior,
      the pretectal area, and substantia nigra. 5-HTir and THir tracts were found in
      lateral and ventral bundles superficially in the brainstem. 5-HTir fibers in the
      spinal cord were located in a large dorsolateral and a smaller ventrolateral
      tract. In the gray matter, a high concentration of 5-HTir fibers were observed in
      areas I-IV and in the lateral motor column of cervical and lumbar enlargements.
      Areas V-VIII and area X were less intensively innervated, with the lowest fibre
      concentration in areas VII-VIII and area X. Throughout the spinal cord, THir
      nerve fibres were located in the same areas but with a lower density. Small
      bipolar 5-HTir and THir cell bodies were found ventromedially to the central
      canal especially in cervical and lumbosacral segments. Large THir cells were
      found in area IX in the caudal sacral and coccygeal spinal cord. THir
      cerebrospinal fluid-contacting cells were also found in the most caudal part of
      the brainstem and the upper cervical spinal cord. The well developed spinal 5-HT
      system and the less developed THir system provides an anatomical explanation for
      the monoaminergic modulation of turtle motoneuron membrane properties, which has
      been observed in electrophysiological experiments.

PMID- 1361495
TI  - Epidermal growth factor receptor distribution in burn wounds. Implications for
      growth factor-mediated repair.
AB  - Epidermal growth factor (EGF) along with several related peptide growth factors
      has been shown both in vivo and in vitro to accelerate events associated with
      epidermal wound repair. EGF and transforming growth factor alpha act by binding
      to a common EGF receptor tyrosine kinase thereby initiating a series of events
      which ultimately regulate cell proliferation. This study examined the
      immunohistochemical localization of EGF receptor (EGF-R) in burn wound margins,
      adjacent proliferating epithelium, and closely associated sweat ducts, sebaceous
      glands, and hair follicles. Tissue specimens removed during surgical debridement
      were obtained from full and partial thickness burn wounds in 32 patients with
      total body surface area burns ranging from 2 to 88%. In the early postburn period
      (days 2-4), prominent staining for EGF-R was found in undifferentiated, marginal
      keratinocytes, adjacent proliferating, hypertrophic epithelium, and both marginal
      and nonmarginal hair follicles, sweat ducts, and sebaceous glands. During the
      late postburn period (days 5-16), EGF-R was depleted along leading epithelial
      margins; however, immunoreactive EGF-R remained intensely positive in the
      hypertrophic epithelium and all skin appendages. Increased detection of
      immunoreactive EGF-R and the presence of [125I]EGF binding in the hypertrophic
      epithelium correlated positively with proliferating cell nuclear antigen
      distributions. Thus, the presence of EGF-R in the appropriate keratinocyte
      populations suggests a functional role for this receptor during wound repair.
      Dynamic modulation in EGF receptor distribution during the temporal sequence of
      repair provides further evidence that an EGF/transforming growth factor alpha/EGF
      R-mediated pathway is activated during human wound repair.

PMID- 1361497
TI  - Neuronal associations in the rat suprachiasmatic nucleus demonstrated by
      immunoelectron microscopy.
AB  - The synaptic associations of neurons in the suprachiasmatic nucleus (SCN) of rats
      were examined by single immunolabeling for somatostatin (SRIH) and arginine
      vasopressin (AVP), and double immunolabeling for SRIH plus AVP and vasoactive
      intestinal polypeptide (VIP) plus AVP. Single immunolabeling showed that SRIH
      neurons, which displayed some somatic and dendritic spines, formed synaptic
      contacts with immunonegative and positive axon terminals. AVP neurons also formed
      synaptic contacts with both immunonegative and positive axon terminals. The
      immunonegative terminals contained small, spherical clear vesicles or flattened
      clear vesicles. A few immunopositive AVP fibers made synapses with immunonegative
      somatic or dendritic spines. Double immunolabeling showed synaptic associations
      between SRIH axons and AVP cell bodies or dendritic processes, and between AVP
      axons and the somata or dendrites of SRIH neurons. These findings suggest a
      reciprocal relation between the two types of neurons. Synaptic contacts between
      AVP neurons and VIP axon terminals were also demonstrated. Previously, we found
      synapses between SRIH axons and VIP neurons. Thus SRIH neurons appeared to
      regulate AVP and VIP neurons. On the basis of these findings, two possible
      oscillation systems of the SCN are proposed.

PMID- 1361498
TI  - Distribution of modulatory inputs to the stomatogastric ganglion of the crab,
      Cancer borealis.
AB  - The pyloric and gastric mill neural networks in the crustacean stomatogastric
      ganglion receive modulatory inputs from more anteriorly located ganglia via the
      stomatogastric nerve. In this study we employed biocytin backfilling and
      immunostaining, as well as electron microscopy, to determine the origin of these
      inputs in the crab, Cancer borealis. Fiber counts from electron micrographs of
      sections through the stomatogastric nerve showed that this nerve contains 55-60
      medium to large diameter fibers (1-13 microns). These fibers were individually
      wrapped by several layers of membrane, presumably glial in origin. There was also
      a single cluster of jointly wrapped, small diameter (< 1 micron) fibers that may
      originate from peripheral sensory somata. Biocytin backfills revealed that
      approximately two thirds of the individually wrapped fibers in this nerve
      originate from somata in the other three ganglia of the stomatogastric nervous
      system, including the paired commissural ganglia and the single oesophageal
      ganglion. There were approximately 20 biocytin-labeled somata in each commissural
      ganglion and 3 somata in the oesophageal ganglion. An additional ten somata were
      localized to the stomatogastric ganglion itself. This accounts for nearly all of
      the medium to large diameter fibers in the stomatogastric nerve. We used double
      labeling with backfills and immunocytochemistry to determine that there are two
      proctolin-immunoreactive neurons and four FMRFamide-like immunoreactive neurons
      among the biocytin-labeled neurons in each commissural ganglion. Both peptides
      modulate neural network activity in the stomatogastric ganglion.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1361499
TI  - Childhood-onset familial porphyria cutanea tarda: effects of therapeutic
      phlebotomy.
AB  - Cutaneous fragility at age 2 years with blistering, scarring, milia, and
      hypertrichosis at age 4 years were noted in an otherwise healthy girl who had no
      family history of porphyria. Results of porphyrin analyses of urine, serum, and
      red blood cells revealed a pattern consistent with porphyria cutanea tarda. Red
      blood cell uroporphyrinogen decarboxylase activity was diminished to
      approximately 50% of normal in the child and in her mother and maternal
      grandmother, who were without symptoms; activity was normal in her sister,
      father, and maternal grandfather. Therapeutic phlebotomies were followed by a
      biochemical and clinical remission.

PMID- 1361500
TI  - Close range shotgun wounds to the foot.
AB  - Presented in a case report of a close range shotgun wound. The nature,
      description, management, and long-term treatment of these wounds are discussed.
      Also presented are the reasons for the differences in short- versus long-range
      shotgun wounds.

PMID- 1361501
TI  - Isolated transverse rupture of the peroneus brevis tendon treated with a free
      split-thickness tendon graft.
AB  - While tendon ruptures are common, isolated transverse rupture of the peroneus
      brevis is an unusual occurrence. The etiology and diagnosis will be discussed in
      this manuscript. Also, the surgical treatment by use of a free split thickness
      tendon graft will be reviewed.

PMID- 1361503
TI  - The identity of Anisakis type II larvae with Anisakis physeteris confirmed by
      restriction fragment length polymorphism analysis of genomic DNA.
AB  - The identity of Anisakis type II larvae with adult A. physeteris was confirmed by
      comparison of restriction fragment length polymorphisms (RFLPs) of 25S ribosomal
      DNA (rDNA). Patterns of RFLPs in larvae were almost identical with those in adult
      worms. Directly labelled 25S rDNA might serve as an appropriate probe with highly
      specific activity for examining RFLPs of larvae and adult worms.

PMID- 1361504
TI  - Unexplained CD4 + T-lymphocyte depletion in persons without evident HIV infection
      -United States.

PMID- 1361502
TI  - [Predictive value of non-specific signs of fetal infection in congenital
      toxoplasmosis].
AB  - AIMS: To study the predictive value of 9 non-specific signs for congenital
      toxoplasmosis. METHOD: The work was carried out as a prospective study comparing
      non-specific signs in 22 fetuses infected with toxoplasmosis and 59 fetuses free
      of the disease. RESULTS: Four of the nine parameters were found to be
      statistically higher in the group of infected fetuses. These are the level of
      leucocytes (p < 0.05) gamma glutamyl transferase (p < 0.001) total M
      immunoglobulin (p < 0.0001) and C4 fraction of complement (p < 0.0001). This last
      sign which is non-specific for infection has never been looked at until now in
      congenital toxoplasmosis but is seems to be of great importance because its
      sensitivity is much greater than of all the other parameters that have been used
      up till now (81%) and the positive predictive value is excellent (72%). On the
      other hand the value of a raised leucocyte count is a matter for discussion.
      CONCLUSION: The presence of even one abnormally raised feature in the fetal blood
      of these non-specific signs is enough to screen for a population which is of high
      risk for congenital toxoplasmosis and sufficient to change our attitude to
      treating the condition.

PMID- 1361505
TI  - Gamma-aminobutyric acid, glutamic acid decarboxylase and tyrosine hydroxylase in
      rat striatum demonstrated by single and dual immunocytochemistry.
AB  - By means of dual ultrastructural immunostaining the followings patterns are
      visualized: gamma-aminobutyric acid (GABA) immunoreactive neurons, dendrites,
      axons and axon terminals and tyrosine hydroxylase (TH) immunopositive fibers,
      varicosities and boutons in rat striatum. Additionally single glutamic acid
      decarboxylase (GAD) immunolabeling is carried out. Four subgroups of GABA and GAD
      immunoreactive striatal neurons are revealed. These neuronal types are identified
      on the basis of sectional diameters, nuclear form and nuclear envelope
      invaginations, quantity of cytoplasm and cell organelles. Plasmalemmal
      appositions between GABAergic and between GABAergic and immunonegative neurons
      are observed. All subgroups of striatal GABAergic neurons contact with GABA and
      GAD immunoreactive, TH immunoreactive and immunonegative boutons. In the striatal
      neuropil numerous GABAergic, dopaminergic and immunonegative axonal endings
      synapsed with dendrites and spines are found out. Massive dopaminergic striatal
      structures using dual immunostaining is evident. Some GABA and GAD immunoreactive
      dendrites are revealed in direct contact with capillary walls.

PMID- 1361506
TI  - Identification of a candidate gene responsible for the high blood pressure of
      spontaneously hypertensive rats.
AB  - OBJECTIVE: We have recently isolated a gene, designated as the SA gene, which is
      more than 10 times more abundantly expressed in the kidneys of spontaneously
      hypertensive rats (SHR) than in those of Wistar-Kyoto (WKY) rats. To address the
      issue whether the SA gene is one of the genes responsible for the hypertension of
      SHR, a genetic cosegregation analysis of the blood pressure values with the
      genotypes in an F2 rat population was undertaken in this study. METHODS AND
      DESIGN: Male F2 rats were bred from SHR and WKY rats. The genotypes of the SA
      gene of the F2 rats were determined by utilizing the StuI restriction fragment
      length polymorphism of the SA gene between SHR and WKY rats. The blood pressure
      values were determined by the tail-cuff method. The effect of the genotype of the
      SA gene on the blood pressure of the F2 rats was analysed by one-way analysis of
      variance. RESULTS AND CONCLUSION: The blood pressure of the F2 rats inheriting
      two SHR alleles of the SA gene was significantly higher than that of the F2 rats
      inheriting two WKY alleles. This indicates that the SA gene, or a gene closely
      linked to it, has a capacity to influence the blood pressure values of the F2 rat
      population. Further studies to identify functions of the SA gene products will be
      necessary.

PMID- 1361507
TI  - HMEC-1: establishment of an immortalized human microvascular endothelial cell
      line.
AB  - The study of human microvascular endothelial cells has been limited, because
      these cells are difficult to isolate in pure culture, are fastidious in their in
      vitro growth requirements, and have a very limited lifespan. In order to overcome
      these difficulties, we have transfected human dermal microvascular endothelial
      cells (HMEC) with a PBR-322-based plasmid containing the coding region for the
      simian virus 40 A gene product, large T antigen, and succeeded in immortalizing
      them. These cells, termed CDC/EU.HMEC-1 (HMEC-1), have been passaged 95 times to
      date and show no signs of senescence, whereas normal microvascular endothelial
      cells undergo senescence at passages 8-10. HMEC-1 exhibit typical cobblestone
      morphology when grown in monolayer culture, express and secrete von Willebrand's
      Factor, take up acteylated low-density lipoprotein, and rapidly form tubes when
      cultured on matrigel. HMEC-1 grow to densities three to seven times higher than
      microvascular endothelial cells and require much less stringent growth medium.
      HMEC-1 will grow in the absence of human serum, whereas microvascular endothelial
      cells require culture medium supplemented with 30% human serum. These cells
      express other cell-surface molecules typically associated with endothelial cells,
      including CD31 and CD36 and epitopes identified by monoclonal antibodies EN4 and
      PAL-E. They also express the cell adhesion molecules ICAM-1 and CD44 and
      following stimulation with interferon-gamma express major histocompatibility
      complex class II antigens. HMEC-1 specifically bind lymphocytes in cell adhesion
      assays. Thus HMEC-1 is the first immortalized human microvascular endothelial
      cell line that retains the morphologic, phenotypic, and functional
      characteristics of normal human microvascular endothelial cells.

PMID- 1361508
TI  - Pulse radiolysis studies of intramolecular electron transfer in model peptides
      and proteins. IV. Met/S:.Br-->Tyr/O. radical transformation in aqueous solution
      of H-Tyr-(Pro)n-Met-OH peptides.
AB  - The intramolecular radical transformation Met/S:.Br-->Tyr/O. in aqueous peptides
      H-Tyr-(Pro)n-Met-OH, n = 0-3, was investigated in the temperature range of 283
      328 K by pulse radiolysis. Corresponding first-order rate constants and
      thermodynamic parameters of activation of electron transfer, Ea and delta S++,
      were determined from kinetic data. The rate constants of the reaction were found
      to decrease exponentially with the number of Pro units and the distance between
      CR atoms of the terminal amino acids, with a correlation coefficient alpha = 3.2
      +/- 0.5 nm-1 at 298 K. Its value appeared to be temperature dependent suggesting
      the occurrence of thermally induced conformational changes in the peptides.
      Analysis of experimental data in terms of known conformational properties of the
      peptides indicates that apparent values of alpha, Ea and delta S++ are probably
      complicated functions of conformation and thermodynamic stability of the
      oligoproline bridge, varying with the number of Pro residues, and of
      intramolecular hydrophobic interactions between side chains of tyrosine and
      methionine. Estimation of the relative efficiency of electron transfer pathways
      through the peptide backbone and through direct and/or water mediated contact
      between groups bearing radical sites led to the conclusion that partitioning of
      electron transfer along these pathways is likely to occur.

PMID- 1361509
TI  - Ethanol radical-induced protein-DNA crosslinking. A radiolysis study.
AB  - Aqueous solutions of double-stranded DNA from calf thymus and bovine serum
      albumin (BSA) were irradiated at pH 7 under N2O and N2 in the presence of 10(-1)
      mol dm-3 ethanol, which was partly 14C-labelled. Ethanol protects DNA from strand
      breakage by scavenging OH radicals, but ethanol radicals induce protein-DNA
      crosslinks. Ethanol radicals react readily with BSA mainly by addition. They
      react also with double-stranded DNA, but produce crosslinking only very slowly.
      Based on these results the following mechanism is proposed: ethanol radicals bind
      to BSA producing protein radicals which become crosslinked to DNA.

PMID- 1361510
TI  - Electron transfer from nucleobase electron adducts to 5-bromouracil. Is guanine
      an ultimate sink for the electron in irradiated DNA?
AB  - Electron transfer to 5-bromouracil (5-BrU) from nucleobase (N) electron adducts
      (and their protonated forms) has been studied by product analysis and pulse
      radiolysis. When an electron is transferred to 5-BrU, the ensuing 5-BrU radical
      anion rapidly loses a bromide ion; the uracilyl radical thus formed reacts with
      added t-butanol, yielding uracil. From the uracil yields measured as the function
      of [N]/[5-BrU] after gamma-radiolysis of Ar-saturated solutions it is concluded
      that thymine and adenine electron adducts and their heteroatomprotonated forms
      transfer electrons quantitatively to 5-BrU. Like the electron adduct of adenine,
      those of cytosine and guanine are rapidly protonated by water. The (protonated)
      electron adduct of guanine does not transfer an electron to 5-BrU, and in the
      case of the (protonated) cytosine electron adduct only partial electron transfer
      is observed. The results can be modelled if the protonated electron adduct
      (protonated at N(3) or at the amino group) of cytosine, CH., which can transfer
      its electron to 5-BrU (k approximately 2 x 10(7) dm3 mol-1 s-1) is transformed in
      a slow tautomerization reaction (k approximately 2.5 x +/- 10(3) s-1) into
      another form C'H. (possibly protonated at C(6) or C(5)) which does not transfer
      an electron to 5-BrU. There is also electron transfer from the electron adduct of
      thymine to cytosine and guanine which serve as electron sinks. The rate constant
      of electron transfer from the thymine electron adduct to cytosine is about 250
      times greater than that of the reverse reaction. The heteroatom-protonated
      electron-adduct of thymidine transfers an electron to 5-BrU more slowly (k = 2.3
      x 10(7) dm3 mol-1 s-1) than the electron-adduct itself (k = 7.2 x 10(8) dm3 mol-1
      s-1). Phosphate buffer-induced protonation of the electron-adduct of thymine at
      carbon (C(6)) prevents electron transfer to 5-BrU. Such phosphate catalysis is
      also observed as an intramolecular process (k approximately 2 x 10(4) s-1) with
      thymidine-5'-phosphate but not with the 3'-phosphate. Phosphate-induced
      protonation at carbon also reduces transfer efficiency for the electron adducts
      of dinucleoside phosphates such as dTpdT and dTpdA. The data raise the question
      whether in DNA the guanine moiety may act as the ultimate sink of the electron in
      competition with other processes such as protonation at C(6) of the thymine
      electron adduct.

PMID- 1361511
TI  - Spectral studies of intermediate species formed in one-electron reactions of
      bovine liver catalase at room and low temperatures. A comparison with peroxidase
      reactions.
AB  - The reactions of native bovine catalase with superoxide and solvated electrons
      have been investigated using three different methods for generation of these
      reducing substrates: gamma-radiolysis of oxygenated or deaerated buffer solutions
      in the presence of an OH radical scavenger; either xanthine or acetaldehyde with
      xanthine oxidase; and low-temperature (77 K) gamma-radiolysis of buffered
      ethylene glycol/water solutions with subsequent annealing of samples at 183 K.
      The first spectral evidence for catalase compound II formation from native
      catalase via reaction with superoxide was obtained. The results are compared with
      results for peroxidase compound II or III formation observed under the same
      experimental conditions. A scheme is proposed to explain these observations
      involving intermediate formation of catalase compounds I and III and the ferrous
      enzyme. The one-electron reduction of catalase and peroxidase by radiolytically
      generated solvated electrons was compared. In the present study the first
      absorption spectrum of a high-spin ferrous catalase which has peaks at 561 and
      594 nm is reported, in comparison with a hemochromogen low-spin ferrous
      peroxidase observed under the same experimental conditions (peaks at 527 and 556
      nm). Both spectra were recorded at 77 K. Data presented in this work also provide
      the first spectral evidence indicating the low temperature (183 K) conversion of
      high-spin ferrous catalase into compound III (oxycatalase) in the presence of
      dioxygen. Under the same experimental conditions low-spin ferrous peroxidase was
      converted into the high-spin ferrous form without oxyperoxidase formation.

PMID- 1361512
TI  - Mutations caused by gamma-radiation-induced double-strand breaks in a shuttle
      plasmid replicated in human lymphoblasts.
AB  - The mutagenicity of open-circular DNA (containing base damage and single-strand
      breaks) and linear DNA (containing base damage, single-strand breaks, and one
      double-strand break) produced in vitro by gamma-irradiation of shuttle vector
      pZ189, was analysed after the plasmid's repair and replication in the human
      lymphoblast line, GM606. By comparing the survival, mutation frequency, and types
      of mutations in descendants from the two DNA forms, the effects of the double
      strand break were determined. The percentage of viable plasmids from linear DNA
      was two-fold lower than that from open-circular DNA, 7.8 versus 14.0 (compared
      with unirradiated, control DNA). The mutation frequency in progenies of the open
      circular plasmid was 4.2 +/- 1.7 x 10(-3), compared with 7.8 +/- 0.1 x 10(-3) in
      progenies of the linear DNA, again, nearly a two-fold difference. Approximately
      59% of the mutations from the linear DNA were deletions and 34% were base
      substitutions. In contrast, only 13% of mutations from open-circular DNA were
      deletions, but 87% were base substitutions. All recoverable deletions were small,
      ranging from 1 to 205 base pairs, and the majority contained direct repeats at
      the deletion junctions, indicating non-homologous recombinations. Thus, mutations
      found among descendants from the linear and open-circular DNAs were qualitatively
      similar but quantitatively different. The data suggests that producing one double
      strand break in DNA by ionizing radiation causes a two-fold increase in both
      lethality and mutation frequency.

PMID- 1361513
TI  - The yield of fission neutron-induced chromatid aberrations in G2-stage human
      lymphocytes: effect of caffeine, hydroxyurea and cytosine arabinoside post
      irradiation.
AB  - To evaluate the influence of inhibitors of DNA synthesis/repair on the yield of
      chromosomal aberrations in the G2 phase of the cell cycle, whole-blood cultures
      of human lymphocytes were exposed to various doses of fission neutrons or X-rays
      and treated post-irradiation during the last 2.45 h before harvesting, with 5 mM
      caffeine, 5 mM hydroxyurea (HU) and 0.05 mM cytosine arabinoside (ara-C). The
      presence of caffeine and HU strongly potentiated the yield of chromatid-type
      aberrations induced by both neutrons and X-rays. No potentiating effect, except
      at the highest dose of neutrons, was observed when irradiated cells were
      subsequently treated with ara-C. Since ara-C strongly potentiated the frequency
      of chromatid aberrations induced in G2 lymphocytes by X-rays, the results
      presented here indicate that fission neutrons produce a smaller proportion of
      lesions, the repair of which can be inhibited by ara-C, compared with the number
      produced by X-rays. In addition, neutron-induced mitotic delay was shortened by
      treatment with caffeine, mainly within the first 2 h after irradiation.

PMID- 1361514
TI  - Chromosome damage induced by high-LET alpha-particles in plateau-phase C3H 10T1/2
      cells.
AB  - Chromosome aberrations induced by X-rays and alpha-particles (LET = 177
      keV/microns) were observed at the first mitosis in C3H 10T1/2 cells released from
      density-inhibited cultures. X-radiation induced more chromosome exchanges than
      breaks (71% vs 27% of total aberrations), while a predominance of breaks (63%)
      was observed after alpha-irradiation. A linear-quadratic dose-response
      relationship was obtained for X-rays, while that for alpha-particles was linear.
      The RBE values for total aberration induction (ranging from 5.1 at low doses to
      4.4 at high doses) were very similar to the RBE for cell killing (from 5.2 to
      4.3). The RBE for dicentric induction (approximately 2) was much lower than the
      RBE for the induction of both breaks (from 7 to 6) and interstitial deletions
      (from 9 to 7). This behaviour supports the hypothesis that chromosome deletions
      play a major role in the malignant transformation of 10T1/2 cells. A high
      correlation between cell killing and number of acentric fragments per cell was
      found. The number of acentrics/cell at the mean lethal dose was about 1.4. This
      number was reduced to 1.0 when asymmetrical interchanges, which generally result
      in very small deletions, were subtracted from acentrics. It could be hypothesized
      that very small deletions could not impair cell survival. However, an alternative
      hypothesis related to the aneuploid state of C3H 10T1/2 cells can be formulated.
      Robertsonian translocations were also observed at the first mitosis. The dose
      response curve of these translocations appears to be very similar to the dose
      response curve for induction of sister chromatid exchanges (observed at the
      second mitosis) reported by other authors studying the same cell line. This
      similarity could indicate a general mechanism of action of radiation on the
      process of recombination of genetic material.

PMID- 1361515
TI  - Heavy ion-induced chromosome breakage studied by premature chromosome
      condensation (PCC) in Syrian hamster embryo cells.
AB  - We have studied induction and repair of chromosome damage induced by high linear
      energy transfer (LET) heavy ions in G1/G0 interphase Syrian golden hamster embryo
      (SHE) cells as revealed by the premature chromosome condensation (PCC) technique.
      The number of chromosome breaks in condensed chromosomes induced by high LET
      heavy ions was higher than those induced by 137Cs gamma-rays. Compared with 137Cs
      gamma rays, the relative biological effectiveness (RBE) for PCC breaks was 1.5
      for 35 keV/microns 4He ions, 1.9 for 77keV/microns 4He ions, and 2.5 for
      530keV/microns 14N ions. Although 95% of the PCC breaks induced by gamma-rays
      rejoined during 8 h post-irradiation incubation, only 35-45% of fragments induced
      by high LET radiations rejoined in the same time. These results suggest that
      there is a difference, spatial or qualitative, in the initial chromosome damage
      produced by high LET radiations and low LET radiations.

PMID- 1361516
TI  - Factors influencing the DNA content of radiation-induced micronuclei.
AB  - The distribution of the DNA content of radiation-induced micronuclei was analysed
      in several cell lines (Chinese hamster, Syrian hamster and mouse NIH-3T3 cells)
      by flow cytometry. Frequency and DNA content of micronuclei were measured
      simultaneously using fluorescence and forward scatter signals of micronuclei and
      nuclei in suspension stained with ethidium bromide. Computerized random breakage
      of chromosomes and random combination of fragments was performed to compare the
      measured micronucleus distributions in synchronized cells irradiated during G1
      phase with calculated distributions. The measured DNA distribution of radiation
      induced micronuclei was found to be influenced by several factors: (1) the DNA
      distribution and the centromeric index of the chromosomes in the various cell
      lines; (2) the cell cycle phase at time of micronucleus measurement due to DNA
      synthesis in micronuclei; (3) the presence of chromosome fragments in
      micronuclei; and (4) the presence of whole chromosomes in micronuclei. These
      factors were shown to be responsible for the previously found large radiation
      induced micronuclei which could not be explained by the classic assumption only
      that radiation-induced micronuclei are mainly produced by single acentric
      fragments.

PMID- 1361517
TI  - Accumulation of cAMP in gamma-irradiated thymocytes and internucleosomal DNA
      fragmentation.
AB  - Ionizing radiation, glucocorticosteroids and chemical inducers of differentiation
      (CID) are cytotoxic to thymocytes, and induce internucleosomal DNA fragmentation.
      Tissue cAMP levels in thymi of irradiated mice were significantly elevated as
      early as 30 min post-irradiation. In contrast, cAMP content in the liver was not
      changed significantly up to 1 h post-irradiation, and then some decrease
      occurred. Irradiation of isolated thymocytes gave essentially the same results as
      after irradiation of animals, and the elevation in cAMP 30 min after the
      irradiation, DNA fragmentation and cell death were linearly related to the dose
      up to 2.5 Gy. The maximal induction of cAMP level occurs in the fractions of
      radiosensitive cortical thymocytes. In thymocytes all CID tested also induced the
      increase in cAMP level with concomitant DNA fragmentation. Unlike ionizing
      radiation, UVC light did not induce cAMP accumulation and DNA fragmentation in
      thymocytes. Treatment of UV-irradiated cells with But2 cAMP did not result in an
      increase in DNA fragmentation. Ionizing radiation induced DNA fragmentation and
      cell death can be prevented by adding the protein kinases inhibitor H-7.
      Theophylline was shown to reduce the cAMP response, DNA fragmentation and cell
      death in gamma-irradiated thymocytes, suggesting that the accumulation of cAMP
      may be partly related to adenosine receptor sites.

PMID- 1361518
TI  - Cytotoxicity of 125I decay in the DNA double strand break repair deficient mutant
      cell line, xrs-5.
AB  - The survival of parental Chinese hamster ovary (CHO) K1 cells and the DNA double
      strand break (DSB) repair deficient mutant, xrs-5 was determined after
      accumulation of 125I decays. Both CHO and xrs-5 cells were extremely sensitive to
      accumulated 125I decays. The D0 values for CHO and xrs-5 cells were 40 and
      approximately 7 decays per cell, respectively. The difference in cell survival
      between CHO and xrs-5 cells was not due to differences in overall 125IUdR
      incorporation, differences in labelling index (LI) or differences in plating
      efficiency (PE). Relative biological effectiveness (RBE) values calculated
      relative to 137Cs gamma radiation survival values (D0 and D10) were higher in xrs
      5 cells compared with CHO cells. Although both CHO and xrs-5 cells have high RBE
      values that correspond to a high sensitivity of CHO and xrs-5 cells to 125I
      decay. The higher RBE observed for xrs-5 cells in combination with the known
      repair defect in xrs-5 cells support the idea that unrepaired DNA double strand
      breaks are lethal to the cell.

PMID- 1361519
TI  - Brain atrophy after foetal exposure to very low doses of ionizing radiation.
AB  - Acute, high dose-rate, exposure of the rat embryo on day 15 post-conception (PC)
      causes a reduction of brain weight in adult life that is proportional to the dose
      received. Doses as low as 10 mGy of 600 keV neutrons, from a Van de Graaff
      accelerator, or 100 mGy of 250 kV X-rays are capable of eliciting a significant
      effect. The relative biological effectiveness for acute neutron exposure compared
      with 250 kV X-rays was 3.5. A brain weight reduction was also observed after
      gamma-ray exposures protracted over 4 or 6 days, during cerebral corticogenesis.
      The dose-rate reduction factor was only 1.5 for exposure from days 12 to 16 PC
      and 3.3 for exposure from days 14 to 20 PC. In relation with the decrease in
      brain weight, the cingulum bundle, a myelinated structure associated with the
      corpus callosum, displayed a significant reduction in size. The implications of
      these observations for human exposures are discussed.

PMID- 1361520
TI  - Time course for the hazard of radiation-induced pneumonitis death in mice.
AB  - The form of the hazard function for radiation-induced pneumonitis death in mice
      was investigated. 'Hazard' refers to the instantaneous failure rate at a
      specified time, conditional upon non-failure to that time. Thus, the hazard
      function describes the time profile for the risk of pneumonitis death among still
      surviving subjects. Single-dose lethality data from nine previously published
      studies involving irradiation of the lung were combined. Sufficient data were
      then available to estimate the hazard for eight different dose groups (dose range
      12-15 Gy). The results of this study suggest that there are multiple distinct
      peaks in the hazard function for radiation pneumonitis, corresponding to distinct
      waves of death separated by an average interval of 33 days. The times of the peak
      hazards are dose dependent, with the peak hazards occurring earlier after larger
      doses, and the values of the hazards at the peaks are also dose dependent, with
      larger doses corresponding to a greater risk of death. The implications of a
      multiply-peaked hazard function for the possible mechanisms of response to whole
      lung irradiation are discussed.

PMID- 1361521
TI  - Rearrangements of the upstream regulatory region of human papillomavirus type 6
      can be found in both Buschke-Lowenstein tumours and in condylomata acuminata.
AB  - Clinically malignant Buschke-Lowenstein tumours and benign condylomata acuminata
      are caused by human papillomaviruses (HPVs), predominantly HPV-6 and -11. In some
      cases, the HPV-6 genomes found in Buschke-Lowenstein tumours and in verrucous
      carcinomas differ from HPV-6b isolated from a benign genital wart, by
      rearrangements of the upstream regulatory region (URR). To evaluate the frequency
      and role of mutations of the URR of HPV-6 we analysed 42 condylomata acuminata
      and four Buschke-Lowenstein tumours by the polymerase chain reaction and
      restriction enzyme cleavage. Using only four different restriction enzymes we
      could demonstrate four distinct restriction patterns, indicating that naturally
      occurring HPV-6 isolates display a high degree of DNA polymorphism within the
      URR. One Buschke-Lowenstein tumour and two condylomata acuminata yielded
      rearranged URRs with DNA duplications. All three lesions harboured multiple HPV-6
      variants, suggesting that cellular or environmental factors facilitate the
      development of rearrangements. Therefore, rearrangements of the URR may represent
      only secondary events in condylomata acuminata and Buschke-Lowenstein tumours
      which do not necessarily confer a higher malignant potential to the infected
      cell.

PMID- 1361522
TI  - Detection of proteinase K-resistant prion protein and infectivity in mouse spleen
      by 2 weeks after scrapie agent inoculation.
AB  - The sequential accumulation of the protease-resistant form of the endogenous
      prion protein (PrP-res) was compared to levels of scrapie infectivity in the
      spleen and brain of scrapie-infected mice at various times after inoculation. In
      mouse spleen PrP-res was detected 1 week after inoculation, and increased 65-fold
      between 1 and 3 weeks post-inoculation and an additional 15-fold during the next
      17 weeks. Infectivity in spleen reached a maximum plateau level by 3 weeks. In
      contrast, in mouse brain PrP-res was not detected until 8 weeks after inoculation
      and then increased 200-fold during the next 12 weeks. During this same time,
      infectivity increased approximately 10,000-fold. Therefore, in both spleen and
      brain of scrapie-infected mice accumulation of PrP-res and infectivity appear to
      be associated. However, it was not possible to show quantitative correlations
      between PrP-res detection and infectivity, perhaps owing to the inaccuracy of the
      infectivity assay.

PMID- 1361523
TI  - Excitotoxic cell death.
AB  - Excitotoxicity refers to the ability of glutamate or related excitatory amino
      acids to mediate the death of central neurons under certain conditions, for
      example, after intense exposure. Such excitotoxic neuronal death may contribute
      to the pathogenesis of brain or spinal cord injury associated with several human
      disease states. Excitotoxicity has substantial cellular specificity and, in most
      cases, is mediated by glutamate receptors. On average, NMDA receptors activation
      may be able to trigger lethal injury more rapidly than AMPA or kainate receptor
      activation, perhaps reflecting a greater ability to induce calcium influx and
      subsequent cellular calcium overload. It is possible that excitotoxic death may
      share some mechanisms with other forms of neuronal death.

PMID- 1361525
TI  - The erbB-3 gene in human pancreatic cancer.
AB  - Abnormalities of the type 1 growth factor receptor family have been implicated in
      the pathogenesis of pancreatic cancer. There is evidence for a potential
      autocrine loop involving overexpression of the epidermal growth factor (EGF)
      receptor and its ligands, as well as overexpression of the erbB-2 receptor. A
      third member of this receptor family, erbB-3, has recently been recognized and
      found to be abnormally expressed in some types of human cancer. In this study we
      show that overexpression of the erbB-3 protein occurs very frequently in
      carcinoma of the exocrine pancreas and also in chronic pancreatitis. We found no
      evidence of amplification or rearrangement of the erbB-3 gene by Southern blot
      analysis of DNA from pancreatic cancer cells lines.

PMID- 1361524
TI  - P-glycoprotein expression in brain tumors.
AB  - Overexpression of P-glycoprotein (P-gp) in cancer cells can result in resistance
      to several chemotherapy agents (multidrug resistance) including doxorubicin and
      vincristine. The drugs to which resistance develops also penetrate the blood
      brain barrier poorly. P-gp expression in brain capillary endothelial cells
      suggests that P-gp may restrict drug entry into brain tumors and thus be another
      mechanism of drug resistance. To seek evidence for either of these roles in the
      drug resistance of brain tumors, we examined the location of expression of P-gp
      in 49 brain tumors, using an anti-P-gp mouse monoclonal antibody and
      immunohistochemistry. P-gp expression was observed in tumor cells of two
      glioblastomas and a meningeal sarcoma but not in low-grade primary or metastatic
      tumors. In low-grade primary tumors, P-gp was present in all vascular endothelial
      cells. In the vascular endothelial cells of anaplastic primary brain tumors and
      brain metastases, P-gp expression was heterogeneous or absent. These findings are
      consistent with a role for P-gp in the resistance of some brain tumors to
      chemotherapy agents.

PMID- 1361526
TI  - Production and characterization of a polyclonal antibody to the c-erbB-3 protein:
      examination of c-erbB-3 protein expression in adenocarcinomas.
AB  - A polyclonal rabbit antibody was raised to the c-erbB-3 protein using a synthetic
      peptide corresponding to amino acids 1229-1241 of the predicted protein sequence
      of c-erbB-3. In Western blot analysis this antibody detects a single band at
      approximately 165 kD in a c-erbB-3 transfected (293/HER-3) human cell line. c
      erbB-3 protein expression was then examined in a variety of adenocarcinomas.
      Expression of c-erbB-3 protein was indicated by membrane and/or cytoplasmic
      tumour cell immunoreactivity in formalin-fixed, paraffin-embedded tissue
      sections. c-erbB-3 protein was detected in a series of 13 out of 14 primary
      breast carcinomas, 3 of 5 gastric adenocarcinomas, 8 of 9 colonic
      adenocarcinomas, 2 of 9 prostatic adenocarcinomas, 0 of 6 renal cell carcinomas,
      1 of 4 primary lung adenocarcinomas, and 5 of 7 endometrial adenocarcinomas.
      Immunohistochemical expression of the c-erbB-3 protein appears to be a relatively
      common event in adenocarcinomas, and further studies are now warranted to
      establish the role of the c-erbB-3 protein in neoplasia.

PMID- 1361527
TI  - Epidermotropism of T cells correlates with intercellular adhesion molecule
      (ICAM1) expression in human papillomavirus (HPV)-induced lesions.
AB  - Adhesion molecules play an important role in inflammatory reactions. Among them,
      ICAM1, a ligand for the lymphocyte function-associated antigen (FLA1) of
      leucocytes, may be expressed by antigen-presenting cells and keratinocytes in
      various inflammatory disorders. As cell-mediated immune responses play a great
      role in HPV infections, we investigated the expression of ICAM1 and correlated it
      with the presence of LFA1-positive cells by immunohistochemistry on serial frozen
      sections of a series of non-regressing cutaneous and mucosal HPV-induced lesions.
      ICAM1 expression by keratinocytes was observed only in intensely infiltrated
      lesions of condylomas and laryngeal papillomas. Its induction was usually
      correlated with the presence of LFA1-positive cells (mainly CD8-positive cells)
      which were in close apposition to ICAM1-positive proliferative epithelial cells
      expressing also, in some cases, HLA-DR antigen. ICAM1 was not correlated with the
      presence of HPV DNA or viral antigen. In moderately infiltrated lesions,
      keratinocytes did not express ICAM1, and LFA1-positive cells were not observed in
      the epidermis. In all lesions, ICAM1 was more intense on endothelial cells than
      in normal skin; infiltrating cells (lymphocytes and dendritic cells) may also
      express this antigen but intraepithelial Langerhans cells were devoid of any
      labelling. These studies provide further evidence that T-lymphocyte mechanisms
      are important in the host response to HPV-induced lesions. ICAM1 expression
      correlates with a lesional infiltrate but not with HPV infection and probably
      results in a more efficient initiation of the immune reaction.

PMID- 1361528
TI  - Effect of cromakalim on the smooth muscle of the cat gastric antrum.
AB  - The effect of the K(+)-channel opener cromakalim (BRL 34915) on the electrical
      and contractile activity of the smooth muscle of the cat gastric antrum has been
      studied. Cromakalim induced a concentration-dependent inhibition of the
      contractions and shortening of the sustained partial repolarization phase of the
      plateau action potential. High concentrations of cromakalim produced
      hyperpolarization and shortening of the repolarization and depolarization phases
      of the plateau action potential. The K(+)-channel blockers 4-aminopyridine (10(
      2) M) and tetraethylammonium (10(-2) M) decreased the effect of cromakalim on the
      phasic contractions, while glibenclamide (5 x 10(-5) M) completely abolished it.
      We suggested that the inhibitory effect of cromakalim on the electrical and
      contractile activity of the gastric antrum smooth muscle is due to the cromakalim
      induced increase of the outward K(+)-current through glibenclamide-dependent K(+)
      channels.

PMID- 1361529
TI  - Calcium antagonism by cobalt ions on contraction of guinea-pig taenia coli.
AB  - In guinea-pig taenia coli, cobalt ions (Co2+) inhibited the tonic response to a
      highly concentrated K+ solution (high-K+, 40 mM) more strongly than the phasic
      response. Co2+ displaced Ca2+ concentration-response curves to the right,
      inhibited the increase in tissue calcium content caused by high-K+, and inhibited
      Ca2+ binding at low affinity sites more than at high affinity sites. After
      treatment with Co2+, the tonic tension caused by high-K+ was not restored by a
      wash with normal medium, but it was restored by a wash with EDTA. The cobalt
      remaining in muscles was almost completely eliminated after a 20-30 min wash with
      EDTA. The results suggest that Co2+ binds chiefly to the surface membrane of
      taenia coli. Co2+ probably reduced the tension in response to high-K+ mainly by
      inhibiting Ca2+ influx rather than by affecting Ca2+ release.

PMID- 1361530
TI  - Ultrastructural alterations and DNA synthesis of renal cell nuclei following
      cisplatin or carboplatin injection in rats.
AB  - To clarify the difference in nephrotoxicity between cisplatin and carboplatin,
      ultrastructural alterations and DNA synthesis of renal cell nuclei were studied
      in Sprague-Dawley rats which had received intravenously either cisplatin or
      carboplatin at an equitoxic dose. Twelve hours after cisplatin injection,
      nucleolar segregation accompanied by aggregated nuclear heterochromatin was
      observed in the third segment of the proximal tubules. Seventy-two hours after
      cisplatin injection, nuclear damage was more widespread while regenerative cells
      were also observed. Nuclear damage was not observed in the carboplatin-treated
      rats. Nuclear DNA synthesis of renal cells was suppressed at 8, 12 and 24 h and
      was accelerated at 72 h after cisplatin injection. Carboplatin did not suppress
      nuclear DNA synthesis at any time. The results indicate that cisplatin, but not
      carboplatin, can affect the renal cell nuclei. Cisplatin-induced nephrotoxicity
      is related to its effects on renal cell nuclei.

PMID- 1361531
TI  - Selective bronchodilators from 1-(5'-oxohexyl)xanthines.
AB  - A series of twenty one 1-(5'-oxohexyl)xanthines substituted with alkyl chains at
      the N3 and N7 positions of the xanthine nucleus were prepared and their relaxant
      activity in guinea-pig isolated tracheal muscle and positive chronotropic
      activity in isolated right atrium of guinea-pig were compared. The tracheal
      relaxant activities were markedly increased with alkyl chain length at the N3
      position, but decreased by the N7 alkylation. The positive chronotropic
      activities in the right atrium were increased by introduction of an n-propyl
      group at the N3 position but decreased by substitution of longer alkyl chains,
      and the action on the heart was diminished by N7 substitution. The activities of
      compounds on cAMP-phosphodiesterase (PDE) and binding of [3H]8-cyclopentyl-1,3
      dipropylxanthine were measured in the homogenate of tracheal muscle and the
      membrane preparation of cerebral cortex, respectively. No relationship among
      tracheal muscle relaxant activity, cAMP-PDE inhibitory activity and adenosine
      antagonism of these xanthines was observed, and other action mechanisms should be
      considered for their relaxant activities. This study indicated that N3 alkylation
      is important for the selectivity for tracheal muscle, while the introduction of
      long alkyl chains such as n-butyl and n-pentyl groups at the N3 and N7 positions
      diminished the potency for the right atrium in guinea-pigs. 3-n-Pentyl- and 7
      methyl-3-n-pentyl-1-(5'-oxohexyl)xanthines showed much higher bronchoselectivity
      than oxpentifylline and theophylline.

PMID- 1361532
TI  - Pharmacokinetic interactions between isoniazid and theophylline in rats.
AB  - Pharmacokinetic interactions between isoniazid and theophylline were studied in
      male Wistar rats, 206 +/- 17 g. Concomitant oral administration of 2 x 5 mg kg-1
      isoniazid accelerated slightly the disposition of theophylline (10 mg kg-1, i.v.)
      whereas 2 x 25 mg kg-1 isoniazid slowed it marginally. The differences in
      distribution volume, systemic clearance and area under the concentration-time
      curve (AUC) between the high and the low dose, however, were statistically
      significant. One week pretreatment with 10 mg kg-1 isoniazid tended towards
      inhibition (significant decrease of systemic clearance, increase of AUC) and 50
      mg kg-1 to acceleration (decrease of half-life, mean residence time and AUC,
      increase of systemic clearance) of theophylline disposition. After oral
      pretreatment with 20 mg kg-1 theophylline, neither the kinetics of free isoniazid
      (50 mg kg-1, i.v.) and the amount acetylated nor the acetylation indices differed
      from the controls. There was no evidence that concomitant or subacute
      administration of different doses of isoniazid affects major metabolic pathways
      of theophylline or that prolonged theophylline treatment interacts with the N
      acetylation capacity.

PMID- 1361533
TI  - Effect of uraemia and anephric state on the pharmacokinetics of tenoxicam in the
      rat.
AB  - Renal alterations, uraemia and nephrotic syndrome induced in experimental animals
      caused a reduction in the plasma albumin concentration of 25 and 30%,
      respectively. As a result of this decrease, the unbound fraction of tenoxicam in
      uraemic rats (0.06 +/- 0.02) and in anephric rats (0.11 +/- 0.08) increased with
      respect to the control group (0.03 +/- 0.004). The induced hypoalbuminaemia did
      not modify the blood to plasma concentration ratio. Both plasma clearance (CL)
      and apparent volume of distribution at steady-state (Vdss) rose significantly
      with the increase in the unbound fraction: (Vdss 55 +/- 6 mL (control rats); 69
      +/- 12 mL (uraemic rats); 96 +/- 30 mL (anephric rats); CL = 7 +/- 1 mL h-1
      (control rats); 12 +/- 4 mL h-1 (uraemic rats); 15 +/- 7 mL h-1 (anephric rats)).
      Tenoxicam elimination was found to be restrictive, with an extraction ratio less
      than 0.1 in the three groups. The induction of nephrotic syndrome was observed to
      have a significant effect on intrinsic metabolic activity, intrinsic clearance of
      tenoxicam being reduced by 30% in the anephric rats (161 +/- 38 mL h-1) with
      respect to the values obtained in the control group (228 +/- 22 mL h-1).

PMID- 1361534
TI  - Pharmacokinetic study of gadolinium-DOTA in control and streptozocin diabetic
      rats.
AB  - The pharmacokinetics of gadolinium tetraazacyclododecanetetraacetic acid (Gd
      DOTA), a contrast agent used in magnetic resonance imaging, have been evaluated
      in control and streptozocin-diabetic rats of different ages. In control rats, an
      age-related decrease in the Gd-DOTA elimination rate was noted, supported by a
      significantly lower apparent total body clearance and a significantly higher mean
      residence time. In diabetic rats, a similar but less important age-related change
      in the mean residence time and the apparent total body clearance was observed.
      Regardless of age-related differences in the pharmacokinetic parameters, a
      diabetic state induced several alterations in the Gd-DOTA pharmacokinetic
      parameters. The apparent total body clearance was significantly higher and the
      mean residence time significantly lower in diabetic rats indicating a higher
      elimination rate of Gd-DOTA. An important age-related increase in the volume of
      distribution at steady-state was noted in diabetic rats.

PMID- 1361535
TI  - Disposition of heptabarbitone in the rat: identification of a new metabolite by
      tandem mass spectrometry.
AB  - The purpose of this study was to elucidate the structure of a metabolite of
      heptabarbitone, the occurrence of which was reported previously in a number of
      pharmacokinetic and pharmacodynamic modelling studies. By application of
      thermospray liquid chromatography (tandem) mass spectrometry, the identity of the
      metabolite was proposed to be 5-ethyl-5-(1',[3' or 6']-cycloheptadienyl)
      barbituric acid. By measuring the ratios between the areas under the
      concentration time curves of the metabolite and heptabarbitone after
      administration of three different intravenous dosages of heptabarbitone, it was
      shown that the exposure to the metabolite is directly correlated with the
      exposure of heptabarbitone.

PMID- 1361536
TI  - Binding of [3H]haloperidol to dopamine D2 receptors in the rat striatum.
AB  - The present study was designed to examine the properties of [3H]haloperidol
      binding to dopamine D2-receptors in rat striatum membranes, displacement
      potencies of various chemicals and differences between the affinities of various
      chemicals and two new 5-hydroxytryptamine (5-HT2) receptor antagonists, MCI-9042,
      (+/-)-2-(dimethylamino)-1-[[o-(m-methoxyphenetyl)phenoxy]methyl]et hyl hydrogen
      succinate hydrochloride and one of its metabolites. The plots of specific binding
      for the striatum membranes obtained from the Scatchard analysis using
      [3H]haloperidol were monophasic when non-specific binding was determined with 10
      microM chlorpromazine, and the Kd and Bmax values were 7.42 +/- 1.03 nM and 1.58
      +/- 0.20 pmol (mg protein)-1 (n = 10), respectively. The displacement potencies
      of D2 receptor, 5-HT2 receptor, histamine H1-receptor, and adrenoceptor
      antagonists were characterized by [3H]haloperidol binding to D2 receptors. The
      pKi values of a new antiplatelet agent, MCI-9042, and its metabolite were 5.02
      and 5.53, respectively, and these values were lower than those of the D2-receptor
      antagonists, fluphenazine, spiperone, haloperidol, prochlorperazine,
      chlorpromazine, thioridazine, and sulpiride. They were also lower than the pKi
      values of the 5-HT2-receptor antagonists, pirenperone, ketanserin, methysergide,
      and mianserin. We conclude that the binding site of [3H]haloperidol in the rat
      striatum is the D2 receptor, that MCI-9042 and its metabolite have lower
      affinities for D2 receptors than for 5-HT2 receptors, and that this radioreceptor
      assay is useful for assessing the affinities of various agents.

PMID- 1361537
TI  - Effect of fenbufen on the entry of new quinolones, norfloxacin and ofloxacin,
      into the central nervous system in rats.
AB  - The entry of two new quinolone antibacterial agents, norfloxacin and ofloxacin,
      into the central nervous system (CNS) of rats, and the effect of fenbufen on this
      was investigated. At various times after the administration of a bolus
      intravenous dose of norfloxacin or ofloxacin (10 mg kg-1) with or without
      fenbufen (20 mg kg-1), serum and cerebrospinal fluid (CSF) samples and whole
      brain were collected from the rats and the concentration of norfloxacin or
      ofloxacin in each sample was determined. Serum concentrations of both quinolones
      declined biexponentially with time and were significantly elevated by
      coadministration with fenbufen at the terminal phase. The fractions of these
      quinolones bound to serum protein were not altered by coadministration with
      fenbufen. Coadministered fenbufen raised the brain concentrations of both
      quinolones but did not affect their brain to serum unbound concentration ratios.
      In contrast, CSF to serum unbound concentration ratios as well as CSF
      concentrations of norfloxacin and ofloxacin were elevated by coadministration
      with fenbufen. Apparent diffusional clearances between blood and CSF of
      norfloxacin and ofloxacin estimated by the physiological model analysis increased
      by 1.9 and 2.6 times, respectively, after coadministration with fenbufen. These
      findings suggest that coadministered fenbufen may facilitate the entry of
      norfloxacin and ofloxacin into the CNS.

PMID- 1361538
TI  - Enantioselective pharmacokinetics of alpha-fluoromethylhistidine in rats and its
      comparison with histidine.
AB  - The enantiomer-specific pharmacokinetics of histidine and its analogue, alpha
      fluoromethylhistidine (FMH), were investigated in rats. After bolus intravenous
      administration of each enantiomer of histidine or FMH at a dose of 40.3 mg kg-1
      as free base equivalents, the plasma concentrations of L-histidine, D-histidine,
      (S)-FMH and (R)-FMH decreased biexponentially with half-lives of 39.2, 20.8, 32.8
      and 25.0 min, respectively, in the elimination phase. Although the concentration
      of L-histidine in the plasma was lower than that of D-histidine, there was no
      large difference in plasma concentration-time curves of the enantiomers of FMH.
      The apparent total clearance of L-histidine from rat plasma was about 4 times
      that of D-histidine or the enantiomers of FMH. L-Histidine was quickly
      transferred to the peripheral tissues where the concentrations also decrease
      biphasically. L-Histidine penetrated more rapidly into the brain than either its
      D-enantiomer or a compound closely related in structure such as FMH. However, the
      disappearance of L-histidine from the various brain regions was very rapid. In
      contrast, brain/plasma ratios of D-histidine and (S)-FMH increased continuously
      after injection of these compounds, indicating that D-histidine or (S)-FMH
      partitioned into the brain and was very slowly removed from the brain; (R)-FMH
      was not distributed to the brain. These results suggested stereoselectivity in
      disposition of histidine and FMH enantiomers in rats.

PMID- 1361539
TI  - Gastric H+, K(+)-ATPase inhibition by catechins.
AB  - Five catechins, (+)-catechin, (-)-epicatechin, (-)-epicatechin gallate, (-)
      epigallocatechin and (-)-epigallocatechin gallate, inhibited gastric H+, K(+)
      ATPase activity with IC50 values ranging from 1.7 x 10(-4) to 6.9 x 10(-8) M,
      with (-)-epigallocatechin gallate as the most potent inhibitor. The intensity of
      inhibitor activity paralleled the number of phenolic hydroxy groups in the
      molecule. The inhibition of the enzyme by (-)-epicatechin was competitive with
      respect to ATP and noncompetitive with respect to K+. These findings suggest that
      the anti-secretory and anti-ulcerogenic effects of catechins previously reported,
      are due to their inhibitory activity on gastric H+, K(+)-ATPase.

PMID- 1361540
TI  - Gastric anti-ulcer activity of silymarin, a lipoxygenase inhibitor, in rats.
AB  - Oral treatment with silymarin was found to be effective in the prevention of
      gastric ulceration induced by cold-restraint stress, in rats. Statistically
      significant ulcer index values with respect to the control group, were observed.
      In 6 h pyloric-ligated animals silymarin showed a significant reduction in the
      number and severity of the ulcers; however, it did not alter the gastric
      secretion volume or acidity although histamine concentration was significantly
      decreased. In absolute ethanol-induced ulcers, treatment with silymarin 1 or 2 h
      before the anti-ulcerogenic agent, did not prevent the formation of gastric
      lesions. Furthermore, the hexosamine content was decreased significantly, but the
      total protein output was enhanced, showing similar values to those with the
      standard drug, carbenoxolone. These results suggest that the anti-ulcerogenic
      effect of silymarin could be related to its inhibitory mechanism of enzymatic
      peroxidation by the lipoxygenase pathway, avoiding leukotriene synthesis.

PMID- 1361541
TI  - High molecular weight protein aggregates formed in the liver of the rat following
      large doses of paracetamol.
AB  - Paracetamol (200 and 500 mg kg-1) was given intraperitoneally to rats pretreated
      with 3-methylcholanthrene for 3 days. Glutamic oxalacetic acid transaminase (GOT)
      activity in plasma increased in rats receiving 500 mg kg-1 paracetamol. Plasma
      GOT activity was low at the dose of 200 mg kg-1, but the same dose to diethyl
      maleate pretreated rats increased the GOT activity. High mol. wt protein
      aggregates were found to be formed in liver homogenates and microsomes of rats
      which showed high plasma GOT activity, accompanied by depletion of hepatic
      glutathione. The formation of protein aggregates in the liver of rats following
      large doses of paracetamol suggests a contribution of lipid peroxidation to
      paracetamol-induced hepatotoxicity.

PMID- 1361542
TI  - In-vitro protein binding interaction between a metabolite of triflusal, 2-hydroxy
      4-trifluoromethylbenzoic acid and other drugs.
AB  - 2-Hydroxy-4-trifluoromethylbenzoic acid (HTB) is the main active metabolite of
      triflusal, an antiplatelet drug. The in-vitro binding of HTB to human serum was
      studied in the presence of different drugs. The results indicate that no
      statistically significant changes are observed in the HTB binding in the presence
      of caffeine, theophylline, glisentide, enalapril, cimetidine or warfarin. The
      free fraction of HTB increases significantly in the presence of the non-steroidal
      anti-inflammatory drugs studied: diclofenac, ibuprofen, indomethacin, naproxen,
      piroxicam and salicylic acid. At high concentrations, HTB displaces these anti
      inflammatory drugs and also glisentide and warfarin from their protein binding
      sites.

PMID- 1361543
TI  - The effects of calcitonin nasal preparations and their excipients on mucociliary
      clearance in an ex-vivo frog palate test.
AB  - The topical tolerability of the commercial preparation of 1-7 Asu-eel and salmon
      calcitonin with 2% ammonium glycyrrhyzinate and 0.01% benzalkonium chloride,
      respectively, and of their excipients mixture in solution with increasing
      concentrations of ammonium glycyrrhyzinate and benzalkonium chloride,
      respectively, were assessed by investigating their effects on the mucociliary
      transport velocity in the ex-vivo frog palate preparation. This preparation
      provides an integrated biological model readily usable in the laboratory which
      closely resembles human nasal mucociliary clearance mechanism and can be used for
      rapid testing and toxicity of agents proposed for topical administration in the
      upper and lower airways. Frog-Ringer control, 1-7 Asu-eel and salmon calcitonin
      commercial spray preparations and the excipients plus 2% ammonium glycyrrhyzinate
      and plus 0.01% benzalkonium chloride did not modify significantly the mucociliary
      transport velocity, confirming their very good tolerability on ciliated
      epithelium. Higher concentrations of ammonium glycyrrhyzinate (10 and 20%) caused
      significant slowing, on average -32 and -55%, respectively. Higher concentrations
      of benzalkonium chloride (0.05 and 0.1%) also caused significant slowing, on
      average, -43.5 and -87%, respectively.

PMID- 1361544
TI  - The binding of the antimalarial arteether to human plasma proteins in-vitro.
AB  - The binding of the novel antimalarial drug, arteether, to human plasma, pure
      albumin and alpha 1-acid glycoprotein has been investigated by ultrafiltration,
      using [14C]arteether. The protein binding in plasma obtained from 11 healthy male
      subjects ranged from 73.4 to 81.8% bound, with a mean of 78.7 +/- 2.1%. The
      binding of drug in plasma was mainly accounted for by binding to albumin and
      alpha 1-acid glycoprotein. Scatchard analysis of the binding data revealed that
      the binding affinity of arteether to alpha 1-acid glycoprotein is much greater
      (20-fold) than that to albumin. This suggests that alpha 1-acid glycoprotein is
      the more important binding protein in plasma. This may have clinical importance
      due to alterations in plasma protein binding in patients with malaria, as the
      concentration of alpha 1-acid glycoprotein is markedly increased during malarial
      infection.

PMID- 1361545
TI  - The Ginkgo biloba extract, EGb761, increases synaptosomal uptake of 5
      hydroxytryptamine: in-vitro and ex-vivo studies.
AB  - The Ginkgo biloba extract (EGb 761) added to a synaptosomal fraction prepared
      from mice cerebral cortex modified [3H]5-hydroxytryptamine ([3H]5-HT) uptake in a
      biphasic manner. Between 4 and 16 micrograms mL-1 EGb 761 increased significantly
      the [3H]5-HT uptake (maximum + 23%). A similar increase was also obtained when
      synaptosomes were prepared from the cortex of mice treated orally with EGb 761,
      either acutely (100 mg kg-1, 14 h and 2 h before death) or semi-chronically (2 x
      100 mg-1 kg daily for 4 consecutive days). The in-vitro increase in [3H]5-HT
      uptake induced by EGb 761 was not observed in the presence of 10(-6) M
      clomipramine, a 5-HT-uptake inhibitor. EGb 761 did not increase [3H]dopamine
      uptake by synaptosomes prepared from striatum of mice. We investigated different
      fractions of EGb 761 in order to determine the compounds inducing the increase in
      [3H]5-HT uptake. The BN 52063 extract (corresponding to the EGb 761 devoid of
      flavonoid substances) did not increase [3H]5-HT uptake. The Cp 202 extract
      (corresponding to the EGb 761 devoid of terpenic substances and containing mostly
      flavonoid substances) increased [3H]5-HT uptake. Among the flavonoids, quercetin
      has been tested and had no effect on the [3H]5-HT uptake. Since at the usual
      therapeutic doses of EGb 761, the effective concentrations of the components
      responsible for this increase are likely to be reached in the brain, one may
      suggest that this effect could contribute to the therapeutic effect of EGb 761.

PMID- 1361546
TI  - Brain as an eliminating organ?

PMID- 1361547
TI  - The effects of labetalol and dilevalol on isolated cardiovascular preparations of
      the guinea-pig and rat.
AB  - Differing effects of labetalol and dilevalol on cardiovascular preparations have
      been reported. I have studied the effects of labetalol and dilevalol on the
      contractile responses of the rat and guinea-pig left atria and rat portal vein.
      On the guinea-pig left atria low concentrations of labetalol (> or = 10(-8) M)
      and of dilevalol (> or = 10(-7) M) inhibited to a small extent the responses to
      electrical cardiac stimulation, which is indicative of membrane stabilizing
      activity. Labetalol (> or = 3 x 10(-8) M) and dilevalol (> or = 10(-8) M) caused
      surmountable antagonism of the isoprenaline responses of the atria and the pA2
      values were 8.60 and 8.98 at the beta 1-adrenoceptors of the rat left atria and
      7.90 and 8.31, respectively, on the guinea-pig left atria which has functional
      beta 1- and beta 2-adrenoceptors. Labetalol and dilevalol (both at > or = 10(-7)
      M) attenuated the spontaneous contractile activity of the rat portal vein and the
      attenuation to labetalol at 10(-6) M was abolished by ICI 118,551 which
      illustrates that the labetalol-induced attenuation is beta 2-adrenoceptor
      mediated. The isoprenaline attenuation responses of the portal vein were
      inhibited by labetalol and dilevalol (both at > or = 10(-7) M) and the pA2 value
      for the labetalol at beta 2-adrenoceptors was 7.59. It is concluded that
      labetalol and dilevalol are beta 1-adrenoceptor selective antagonists.

PMID- 1361548
TI  - Fab-bound colchicine appears to adopt Fab fragment disposition in rats.
AB  - The disposition of colchicine-specific Fab fragments and the effect of Fab
      fragment administration on the disposition of colchicine were studied in
      anaesthetized bile duct-cannulated rats. One group of rats (n = 6) received a
      125I-Fab dose of 38 mg kg-1 i.v. The plasma disposition was characterized by a
      volume of distribution of 179 +/- 48 mL kg-1, total body clearance of 1.02 +/-
      0.07 mL min-1 kg-1, t1/2 alpha of 0.17 +/- 0.03 h and t1/2 beta of 1.3 +/- 0.3 h.
      Fab fragments were in part excreted by the renal route (15.6 +/- 6% of the Fab
      dose), while biliary excretion was a minor route (< 2% of the Fab dose). Two
      other groups of rats received 15 micrograms kg-1 colchicine (n = 6) or 15
      micrograms kg-1 colchicine plus 38 mg kg-1 colchicine-specific Fab fragments (n =
      6) by intravenous infusion. Pharmacokinetics of colchicine was markedly altered
      in the Fab-colchicine-treated rats. In this group, distribution volume and total
      body clearance of colchicine were decreased by factors of 22 and 10,
      respectively, compared with the values in the colchicine-treated group and were
      very similar to those of Fab fragments. An 80% reduction of cumulative biliary
      excretion of colchicine was observed in Fab-colchicine-treated rats (P < 0.01).
      The fraction of colchicine dose excreted by the urinary route was 38 +/- 6.9 and
      9 +/- 0.7% respectively in Fab-colchicine- and colchicine-treated groups (P <
      0.01). These data show that during Fab treatment, colchicine followed the
      elimination kinetics of Fab fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361549
TI  - Spectrophotometric method for the determination of carbidopa using neotetrazolium
      chloride.
AB  - A new high-sensitive spectrophotometric method for the determination of
      microquantities of carbidopa is described. The method is based on the reduction
      of neotetrazolium chloride by carbidopa in an alkaline ethanolic medium. The
      formazan formed exhibits an absorption maximum at lambda = 507 nm, with an
      apparent molar absorptivity of epsilon = 6.63 x 10(4) M-1 cm-1 and a
      corresponding Sandell's sensitivity of 3.68 ng cm-2. Beer's law is obeyed over
      the range of 0.10-6.0 micrograms mL-1 while the optimum concentration range is
      0.125-5.0 micrograms mL-1. The regression line equation was calculated as: A =
      0.271C + 0.0023 with a correlation coefficient of 1.0000 (n = 28). The accuracy
      and the precision of the method were considered as very satisfactory. The results
      obtained from the determination of carbidopa using both the described procedure
      and the corresponding USP. XXII and BP 1988 clinical methods were statistically
      compared by means of Student's t-test as well as by the variance ratio F-test,
      and no significant difference was observed.

PMID- 1361550
TI  - Simultaneous determination of bufadienolides in the traditional Chinese medicine
      preparation, liu-shen-wan, by liquid chromatography.
AB  - The bufadienolide compounds (bufalin, cinobufagin and resibufogenin), major
      constituents of Chansu in Liu-Shen-Wan (LSW), were determined by reverse phase
      high performance liquid chromatography. The procedure involves a preliminary
      extraction of the bufadienolides from LSW with chloroform using ultrasonication
      and subsequent evaporation to dryness of the chloroform extract. The residue of
      the chloroform extract was dissolved in methanol and separated on a Merck
      LiChrosorb RP-18 column. Methanol: water (74:26) was used as mobile phase. The
      compounds were satisfactorily separated with good chromatographic peaks. Good
      coefficients of correlation (r > 0.999) were obtained from the calibration of
      peak areas with concentrations for the 3 bufadienolides. Results of analysis
      showed that there were differences between the contents of bufadienolides in 11
      LSW samples of different origin available to the public in Hong Kong where at
      present there is no legal control over the sale of traditional Chinese medicines.
      The variability of quantities of bufadienolides in Chansu may be a hazard to the
      public.

PMID- 1361551
TI  - Uptake of cefadroxil derivatives in rat intestinal brush-border membrane
      vesicles.
AB  - Uptake of cefadroxil and its two acetyl-derivatives, N-acetyl- and O-acetyl
      cefadroxil, into the brush-border membrane vesicles (BBMV) was measured at [pH]o
      = 5.5, 7.4 and [pH]i = 7.4. Both acetyl-derivatives showed a significantly slower
      uptake than cefadroxil at [pH]o = 5.5 and 7.4. Cefadroxil and the two derivatives
      showed a higher uptake rate in the presence of an inward H+ gradient ([pH]o =
      5.5, [pH]i = 7.4). At [pH]o = 5.5, uptake of cefadroxil into BBMV was inhibited
      by N-acetyl-, O-acetyl-, N-BOC-, and N-BOC-O-acetyl-cefadroxil, but not by
      cephalothin and cefuroxime. At [pH]o = 7.4, no inhibition of cefadroxil uptake
      was evident for any inhibitors. There were two different transporters responsible
      for the uptake of cefadroxil at pH 5.5 and 7.4. One is the H(+)-coupled dipeptide
      transport system, and the other is the neutral pH-preferring system. The alpha
      amino group may be essential for the transport of cefadroxil by both transport
      systems. Although the phenolic group in the side chain is not an essential
      functional group of beta-lactam antibiotics, an additional derivation on the
      phenolic group of cefadroxil also inhibited both the H(+)-coupled dipeptide
      transport system and the neutral pH-preferring transport system.

PMID- 1361552
TI  - Effects of nicarbazin on intestinal digestion and absorption of nutrients in the
      rabbit.
AB  - Nicarbazin is an anticoccidial drug, used mainly in birds, which has shown
      several other effects including inhibition of growth and feed efficiency in
      poultry, and stimulation of sugar and amino acid intestinal absorption in rabbit.
      The present work was designed to determine whether nicarbazin added to the feed,
      affects growth and feed intake in rabbit, and whether the continuous ingestion of
      nicarbazin can alter the mechanisms of intestinal nutrient absorption or
      digestion in this species. Nicarbazin, administered at the recommended dose (125
      ppm) had no harmful effects either on growth or on feed intake of animals. After
      treatment for one month with nicarbazin at the dose of 125 ppm added to the feed,
      rabbits displayed a higher transport ability of both D-glucose and L-leucine
      through the enterocyte plasma membranes than did untreated rabbits. These animals
      also showed higher specific activities of two brush-border enzymes, sucrase and
      aminopeptidase N, than the control animals.

PMID- 1361553
TI  - Inhibitory effect of prostaglandin E1 on laurate-induced peripheral vascular
      occlusive sequelae in rabbits: optimized topical formulation with beta
      cyclodextrin derivative and penetration enhancer HPE-101.
AB  - Prostaglandin E1 (PGE1) and its inclusion complexes with beta-cyclodextrin (beta
      CyD) and O-carboxymethyl-O-ethyl-beta-cyclodextrin (CME-beta-CyD) were made as
      topical preparations. The PGE1 preparations, when applied with a penetration
      enhancer, 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101), markedly
      increased the regional blood flow in the ear of rabbits and were longer acting
      than when administered by the intravenous route. Topical application of the PGE1
      preparations significantly protected rabbits against laurate-induced peripheral
      vascular occlusive sequelae; the protective potency increased in the order of
      PGE1 alone = beta-CyD complex < CME-beta-CyD complex preparation. The PGE1
      preparations elicited skin reactions such as erythema and oedema depending on
      their vasodilating actions. These reactions disappeared gradually after removal
      of the preparations, and hence may not be serious obstacles for their safe use.
      These results suggest that combinations of CME-beta-CyD and HPE-101 work
      synergistically to facilitate the entry of PGE1 into the skin, and consequently
      enhance the therapeutic potential of PGE1 in the topical preparation tested.

PMID- 1361554
TI  - Decrease by psychotropic drugs and local anaesthetics of membrane fluidity
      measured by fluorescence anisotropy in Escherichia coli.
AB  - The effects of psychotropic drugs and local anaesthetics on the fluidity of
      Escherichia coli cell membranes were examined. Chlorpromazine was shown to
      increase 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy, indicating that
      it decreased the membrane fluidity. This increase was significant at a
      temperature of more than 24 degrees C. Dibucaine, lignocaine, imipramine,
      tetracaine and procaine also increased the fluorescence anisotropy.

PMID- 1361556
TI  - Comparison of fluoxetine and norfluoxetine enantiomers as inhibitors of
      hexobarbitone metabolism in mice.

PMID- 1361555
TI  - The 3,3'-bis-pyridinium mono-oximes as antidotes against organophosphorous
      intoxication.
AB  - In an attempt to develop effective antidotes against organophosphorous
      intoxication, three new structurally related bispyridinium mono-oximes with a 2
      oxopropane bridge were synthesized. The compounds were evaluated for in-vivo
      therapeutic protection and cholinesterase reactivation in blood and various brain
      regions. In neuromuscular function studies against diisopropyl-fluorophosphate
      and isopropyl methylphosphonofluoridate poisoning, the oximes produced
      significant protection. The compounds produced marked peripheral reactivation and
      beneficial effects on neuromuscular transmission. The reactivation of
      cholinesterase in cerebral cortex by the oximes, in spite of their being
      quaternary salts is a notable feature.

PMID- 1361557
TI  - Some features of Cannabis plants grown in the United Kingdom from seeds of known
      origin.
AB  - The cannabinoid content of UK-grown plants (up to the 6th generation) from
      Moroccan, Sri Lankan and Zambian seedstock was determined by TLC, GLC and HPLC.
      All plants from the 5th and 6th series resembled their parents, and UK-grown
      plants were always much greener than those grown overseas. Cannabinoid content
      remained broadly typical of the source countries. However, tetrahydrocannabinolic
      acid (THCA) consistently predominated over tetrahydrocannabinol (THC) to a far
      greater extent than in the original plants; the THCA/THC ratio was 17 in UK-grown
      plants compared with 2.0 in the plants from the original areas. Two types of
      plant emerged from the Moroccan seedstock, one tending to increased cannabidiol
      (CBD), the other tending to zero levels of this component. The first generation
      Sri Lankan plants revealed one type of plant with an increased CBD/THC ratio (1.7
      compared with 0.11) but this returned to the original value in the succeeding
      generations. Other Sri Lankan plants had low or undetectable levels of CBD.
      Moroccan and Sri Lankan CBD-rich plants did not contain cannabichromene, although
      this cannabinoid was found in THC-rich plants. Zambian plants did not appear to
      show such a pattern. Zambian seedstock plants had total tetrahydrocannabivarin
      (diol and acid) levels greater than THC but the ratio was progressively reversed
      in succeeding generations. The study concludes that the ratios of particular
      cannabinoids is greatly influenced by the environment.

PMID- 1361558
TI  - Transfer of heparin across the human perfused placental lobule.
AB  - A system of dual perfusion of an isolated lobule of term human placenta was used
      as a model to study the transfer of heparin from maternal to foetal circulation.
      The metabolic viability of the system was assessed by measuring beta-HCG and
      alkaline phosphatase levels in both maternal and foetal perfusates. Creatinine
      and antipyrine were used as markers to determine juxtaposition of the maternal
      and foetal circulations. Results of this study indicate that following
      administration of a single bolus dose of heparin into the maternal circulation,
      its concentration declined slowly from 99.01 +/- 2.98 at 15 min to 97.23 +/-
      4.12% and transfer of heparin in the foetal circulation was linear and increased
      from 0.10% +/- 0.05% at 15 min to 0.46 +/- 0.19% over a period of 120 min. The
      maternal (MAUC) and foetal (FAUC) concentration-time integrals were found to be
      70160 +/- 1332 and 340 +/- 30 int. units min mL-1, respectively. Placental
      permeability of heparin and creatinine, calculated as the ratio of foetal
      concentration to the integral maternal-foetal concentration difference, was 8.65
      x 10(-5) +/- 0.80 x 10(-5) and 0.033 +/- 0.006 mL min-1 g-1 of perfused placental
      weight, respectively. These data suggest that heparin was transferred from the
      maternal to the foetal circulation in small quantities.

PMID- 1361559
TI  - The effects of various peptides on human isolated gut muscle.
AB  - The effects of eleven peptides of gastrointestinal origin have been studied on
      the contraction, relaxation and spontaneous activity of circular and longitudinal
      muscle strips from different regions of the human gastrointestinal tract. The
      effects varied with the peptides and sometimes with the region and muscle layer.
      There was either contraction, no effect, or relaxation and/or inhibition of an
      acetylcholine-induced contraction. Responses to some peptides are consistent with
      the possibility that they may contribute directly to the control of motility:
      galanin, neurotensin and substance P might be involved in contraction, and
      vasoactive intestinal peptide, peptide histidine isoleucine and peptide histidine
      methionine might be inhibitory transmitters.

PMID- 1361560
TI  - Transport characteristics of cephalosporin antibiotics across intestinal brush
      border membrane in man, rat and rabbit.
AB  - The uptake of orally active cephalosporins, ceftibuten and cephradine, by
      intestinal brush-border membrane vesicles isolated from man, rat and rabbit was
      studied. In the presence of an inward H+ gradient, ceftibuten but not cephradine
      was taken up into intestinal brush-border membrane vesicles of man and rat
      against the concentration gradient (overshoot phenomenon). In rabbit jejunal
      brush-border membrane vesicles, the uptake of both cephalosporins in the presence
      of an inward H+ gradient exhibited the overshoot phenomenon. In human and rat
      vesicles, the initial uptake of ceftibuten was strongly inhibited by compound V,
      an analogue of ceftibuten, but the uptake of cephradine was not affected by any
      of the cephalosporins tested, whereas in the rabbit brush-border membrane
      vesicles, initial uptake of both ceftibuten and cephradine were markedly
      inhibited by all cephalosporins and dipeptides used. These results suggest that
      the transport characteristics of human and rat intestinal brush-border membrane
      for cephalosporins are comparable, and that rabbit is an inadequate animal for
      investigating the transport characteristics of beta-lactam antibiotics.

PMID- 1361561
TI  - Metabolic activation of sennoside C in mice: synergistic action of anthrones.
AB  - Sennosides A and C directly injected into the caecum of mice showed equal
      purgative activity. Intracaecal administration reduced time to onset of diarrhoea
      induced by sennoside C from about 3 h after oral administration to about 24 min.
      At 2.3 h after oral administration of sennoside C, nearly equimolar amounts of
      aloe-emodin anthrone and rhein anthrone were detected in the large intestine of
      mice. The purgative effect of oral sennoside C could be reduced by pretreating
      mice with chloramphenicol. This was observed as a decreased formation of total
      anthrones in the large intestine. Both anthrones and an equimolar mixture of both
      anthrones directly injected into the caecum exerted a purgative effect, although
      the activity was lower for aloe-emodin anthrone. The intracaecal ED50 values were
      54.5 (24.1-89.6), 11.4 (5.0-15.7) and 11.2 (6.1-14.6) mumol kg-1 for aloe-emodin
      anthrone, rhein anthrone and an equimolar mixture of both anthrones,
      respectively. We concluded that aloe-emodin anthrone and rhein anthrone, formed
      mainly by intraluminal bacterial action, are the true active metabolites of
      sennoside C in mice and that both anthrones synergistically exert their purgative
      effects on mice.

PMID- 1361562
TI  - Transport of paraquat and mexiletine from the blood into the rat intestinal lumen
      and peritoneal cavity.
AB  - Transport of paraquat and mexiletine from the blood into the intestinal lumen and
      the peritoneal cavity was examined after their intravenous administration
      (paraquat: 20 mg kg-1, mexiletine: 10 mg kg-1) to rats. The average amounts of
      paraquat transferred into the intestinal lumen and the peritoneal cavity were
      1.39 and 22.8% of the dose in 120 min, respectively. The average amounts of
      mexiletine transferred into the intestinal lumen and the peritoneal cavity were
      6.1 and 2.5% of the dose in 120 min, respectively. The transfer rate of 3H2O into
      the peritoneal cavity after intravenous administration (1.85 MBq) was greater
      than that into the intestinal lumen. In view of the hydrophilic nature of
      paraquat cation, a solvent drag effect due to movement of water might contribute
      to transport of paraquat from the blood to the peritoneal cavity. Differences in
      transport behaviour across the two membranes could be due to differences in the
      geometrical factors such as the surface area and the distribution of blood
      vessels. Differences might also be due to differences in physicochemistry and
      pharmacological effects of both substances.

PMID- 1361563
TI  - Semicarbazide-sensitive amine oxidase from the smooth muscles of dog aorta and
      trachea: activation by the MAO-A inhibitor clorgyline.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) has been identified in the dog
      trachea and aorta smooth muscles. The dog SSAO is blocked by hydrazine
      inhibitors. SSAOs from several different vascular smooth muscle sources, such as
      the rat and bovine aorta, and human umbilical artery, as well as the bovine
      plasma, are insensitive to the MAO-A inhibitor clorgyline; the dog SSAO on the
      other hand is significantly activated by clorgyline. Two methods, i.e.
      radioenzymatic and fluorometric methods, have been applied to substantiate this
      clorgyline-induced activation. The activation was detected with respect to the
      deamination of different substrates, such as benzylamine, beta-phenylethylamine
      and longer carbon chain aliphatic amines, but not with respect to methylamine.
      The clorgyline effect is reversible, non-competitive and time-independent; it
      depends on electrostatic and hydrophobic interactions between clorgyline and
      hydrophobic regions of the dog SSAO enzyme.

PMID- 1361564
TI  - Contractile responses of chicken rectum to stimulation of Remak's nerve or
      purinoceptors: effect of suramin.
AB  - Stimulation of Remak's nerve produced a rapid contraction of the rectal muscle
      which was resistant to blockade by hyoscine, followed by a slow contractile
      response which was cholinergic. With hyoscine (1 microM) in the Tyrode solution,
      the non-cholinergic contractile response to nerve stimulation was compared with
      the responses to adenosine triphosphate (ATP) and alpha,beta-methylene adenosine
      triphosphate (alpha,beta-Me ATP). In the presence of suramin (300 microM), the
      contractile response to ATP was increased by about 100%, whereas that to nerve
      stimulation was inhibited by approximately 17%. Suramin (60 microM) also
      discriminated between the contractile responses to ATP and nerve stimulation,
      only the former being potentiated by the drug. It seems probable that suramin
      potentiated the action of ATP in the rectum through inhibition of
      ectonucleotidase activity. If so, the potentiation should not extend to
      alpha,beta-Me ATP, as this analogue of ATP is resistant to inactivation by the
      enzyme. Suramin inhibited the contractile response to alpha,beta-Me ATP. Thus the
      neurotransmitter which mediated the hyoscine-resistant contractile response to
      stimulation of Remak's nerve was dissimilar to ATP, in that it was not
      potentiated by suramin and presumably was not inactivated by ectonucleotidase
      activity.

PMID- 1361565
TI  - L-dopa-like regulatory actions of L-threo-3,4-dihydroxyphenylserine on the
      release of endogenous noradrenaline via presynaptic receptors in rat hypothalamic
      slices.
AB  - Effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on the spontaneous
      release and the stimulus(2 Hz)-evoked release of endogenous noradrenaline were
      studied in rat hypothalamic slices with functioning L-aromatic amino acid
      decarboxylase (AADC) and with AADC inhibition. In non-inhibited slices,
      spontaneous release was not modified by L-threo-DOPS at 1 pM-100 nM, tended to
      increase at 1-10 microM and increased at 100 microM. Noradrenaline tissue content
      slightly increased at 100 microM. Stimulated release was concentration
      dependently facilitated at 1-1000 pM and tended to decrease gradually from a
      maximum at 10 nM-10 microM. Under AADC inhibition, spontaneous release
      concentration-dependently increased at 10-100 microM by 60% of the increase seen
      in slices without AADC inhibition. Increase in noradrenaline tissue content was
      abolished. L-threo-DOPS produced a triphasic pattern on stimulated release;
      concentration-dependent facilitation at 1-1000 pM similar to that seen in slices
      with functional AADC, no facilitation at 10-1000 nM, and a concentration
      dependent increment at 10-100 microM. The facilitation at 1 nM was
      stereoselective and was antagonized by (-)-propranolol 10 nM, and no facilitation
      at 100 nM was restored to the maximum by yohimbine 10 nM, DG-5128 10 nM or S
      sulpiride 1 nM. Furthermore, L-threo-DOPS (1-1000 pM)-induced facilitation was
      competitively antagonized by L-dopa methyl ester, a competitive antagonist for L
      dopa, with a pA2 value of 13.6, whereas it was noncompetitively antagonized by (
      )-propranolol.

PMID- 1361566
TI  - Antiarrhythmic, electrophysiological and haemodynamic effects of prolonged oral
      dosing with Org 7797 in the anaesthetized rat.
AB  - The antiarrhythmic, electrophysiological and haemodynamic effects of chronic oral
      administration of Org 7797 ((16 alpha,17 beta)-17-methylamino-oestra-1,3,5(10)
      triene-3, 16-diol-(Z)-2-butonedioate) were studied in rats. During dosing (10 mg
      kg-1 twice a day for 10 days) no effects on the electrocardiogram, monitored in
      conscious animals, were observed despite modest reductions (15-18%) in the
      maximum rate of depolarization of papillary muscle excised 1 or 6 h after
      completion of the dosing regime. Following anaesthesia, Org 7797 reduced the
      severity of arrhythmias induced by coronary artery occlusion and prevented the
      accompanying decrease in the ventricular fibrillation threshold (VFT) at 1 h
      after completion of dosing. By 6 h the effect on VFT had waned but protection
      against ischaemia-induced arrhythmias was retained despite a substantial decrease
      in Org 7797 plasma levels. Drug treatment did not modify arterial blood pressure,
      heart rate or stroke volume. We conclude that Org 7797 given chronically via the
      oral route exerts antiarrhythmic actions which may, at least in part, be due to
      sodium-channel block. In addition, our results suggest the presence of an active
      metabolite. The protective effects of Org 7797 were seen in the absence of
      electrocardiographic or haemodynamic changes suggesting that multiple oral doses
      of Org 7797 do not compromise normal cardiac function.

PMID- 1361567
TI  - [Synthesis of metabolites of mosapramine. II. Synthesis of phenolic metabolites
      of mosapramine and their pharmacological activities].
AB  - Four phenolic metabolites of (+-)-3-chloro-5-[3-(2-oxo-1,2,3,5,6,7,8,8a
      octahydroimidazo[1,2- a]pyridine-3-spiro-4'-piperidino)propyl]-10,11-dihydro-5H
      dibenz [b,f]azepine (mosapramine), a new antipsychotic drug, were synthesized in
      order to determine their chemical structures. Pharmacological activities of the
      three main metabolites were compared with those of mosapramine. The activities of
      the metabolites were far less potent than those of mosapramine.

PMID- 1361568
TI  - Inhibition of adenylate cyclase in the locus coeruleus mediates the hypnotic
      response to an alpha 2 agonist in the rat.
AB  - Recently, we determined that the transduction mechanism for the hypnotic response
      to dexmedetomidine, a highly selective alpha 2 agonist, resides in the locus
      coeruleus (LC) of the rat. Candidates for the effector mechanism of this alpha 2
      adrenoceptor-mediated hypnotic response include inhibition of adenylate cyclase,
      which has been shown to be pivotal to the cellular response of alpha 2 agonists
      in some, but not in all, cases. The LC of rats were stereotaxically cannulated
      with an indwelling catheter, and after the 2nd day, the hypnotic response to 7
      micrograms of dexmedetomidine into the LC (an effective hypnotic dose for 95% of
      animals) was tested. Other groups of rats were pretreated with the permeable
      nonhydrolyzable cyclic AMP (cAMP) analog, dibutyryl cAMP (dB cAMP), at a dose of
      0.2 to 1.2 ng into the LC, or 2.75 to 275 micrograms.kg-1 i.p. rolipram, a cAMP
      specific phosphodiesterase inhibitor, and the hypnotic response to 7 micrograms
      of dexmedetomidine into the LC was tested. Both dB cAMP and rolipram reversed the
      hypnotic response to dexmedetomidine. To test for the specificity of these
      hypnotic-reversing perturbations, rats were pretreated with Rp-adenosine-3',5'
      cyclic phosphorothioate, a cAMP-dependent protein kinase inhibitor, and the
      experiments were repeated. The hypnotic-reversing property of either dB cAMP or
      rolipram could be prevented by blocking cAMP-dependent protein kinase ("A"
      kinase) activity with Rp-adenosine-3',5'-cyclic phosphorothioate.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1361569
TI  - The positive chronotropic effect induced by BRL 37344 and CGP 12177, two beta-3
      adrenergic agonists, does not involve cardiac beta adrenoceptors but baroreflex
      mechanisms.
AB  - The presence of a beta-3 adrenoceptor (in addition to the classical beta-1 and
      beta-2 adrenoceptors) and its involvement in the control of heart rate was
      investigated in the dog. Experiments were carried out in conscious normal and
      sinoaortic denervated dogs (i.e. animals deprived of baroreceptor pathways). In
      normal dogs, infusion of isoproterenol, BRL 37344 (4-[-[(2-hydroxy-(3
      chlorophenyl) ethyl)-amino]propyl]phenoxyacetate) (a beta-3 adrenergic agonist)
      or CGP 12177 (4-[3-t-butylamino-2-hydroxypropoxy]benzimidazol-2- one) (a beta-1
      beta-2 adrenergic antagonist reported to act as an agonist for the beta-3
      adrenergic receptor) increased heart rate with an order of potency: BRL 37344 >
      isoproterenol >> CGP 12177. [125I]Cyanopindolol binding (2-2000 pM) was saturable
      and Scatchard analysis indicated the presence of an homogenous population of
      binding sites. KD was 12.8 +/- 18.5 pM and maximum binding was 94.2 +/- 12.5
      fmol/mg of protein. Competition binding studies on dog heart membranes using 150
      pM [125I] cyanopindolol indicated an order of potency (CGP 12177 > isoproterenol
      > BRL 37344) different from that observed in cardiovascular studies.
      Isoproterenol stimulated adenylate cyclase activity in heart membranes from
      normal dogs, whereas CGP 12177 and BRL 37344 were without any stimulating action.
      The positive chronotropic effects of isoproterenol, BRL 37344 and CGP 12177 were
      accompanied with a reduction in arterial blood pressure. In sinoaortic denervated
      animals, isoproterenol infusion provoked tachycardia and hypotension. BRL 37344
      and CGP 12177 were without any significant effect on heart rate but induced a
      rapid and dramatic hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361570
TI  - Pharmacological characterization of PD 118717, a putative piperazinyl
      benzopyranone dopamine autoreceptor agonist.
AB  - PD 118717 (7-[3-[4-(2-pyrimidinyl)-1-piperazinyl]-propoxy]-2H-1- benzopyran-2-one
      sulfate) proved to be a dopamine (DA) D-2 autoreceptor agonist in biochemical and
      electrophysiological studies in rats and to exhibit an antipsychotic-like profile
      in behavioral tests in rodents and monkeys. In vitro binding studies indicated
      that PD 118717 bound selectively to DA D-2 vs. D-1 receptors and exhibited
      agonist binding properties (biphasic inhibitory curves and GTP shift) similar to
      DA. It also had significant affinity for serotonin-(5-HT)1A but not 5-HT1B and 5
      HT2 receptors. PD 118717 was active in antagonizing the tau-butyrolactone-induced
      accumulation of dopa in rat striatum and mesolimbic regions. PD 118717 also
      depressed the firing of DA neurons in substantia nigra pars compacta of rats. In
      both of the latter tests the effects of PD 118717 were reversed by haloperidol.
      PD 118717 decreased brain DA metabolism, decreased DA utilization, decreased
      accumulation of dopa after inhibition of L-aromatic amino acid decarboxylase,
      stimulated serum corticosterone and inhibited stimulated serum prolactin levels.
      PD 118717 did not alter striatal acetylcholine levels; nor did it induce
      locomotor stimulation or stereotypy in normal animals, suggesting a lack of
      postsynaptic DA stimulation of normosensitive DA receptors. In tests designed to
      reveal even weak postsynaptic DA agonist effects, PD 118717 stimulated locomotor
      activity in 6-hydroxydopamine-lesioned animals and relatively higher doses
      induced a low degree of stereotyped behavior when combined with the DA D-1
      agonist SKF 38393. PD 118717 decreased the accumulation of 5-hydroxytryptophan in
      brain, an effect probably due to an agonist action at 5-HT1A receptors. PD 118717
      decreased spontaneous locomotor activity in rodents, antagonized amphetamine
      stimulated hyperactivity in mice and inhibited Sidman avoidance in monkeys,
      effects seen with antipsychotic agents. Unlike DA antagonist antipsychotics, PD
      118717 did not induce extrapyramidal dysfunction in monkeys. PD 118717 displayed
      behavioral activity after p.o. dosing and its effects did not show tolerance on
      repeated dosing. In conclusion, PD 118717 has the profile of a DA autoreceptor
      agonist in neurochemical and neurophysiological tests and produces effects
      suggestive of antipsychotic efficacy without neurological side effect liability
      in preclinical behavioral tests.

PMID- 1361571
TI  - DuP 734 [1-(cyclopropylmethyl)-4-(2'(4''-fluorophenyl)-2'- oxoethyl)piperidine
      HBr], a potential antipsychotic agent: preclinical behavioral effects.
AB  - It has been suggested that sigma receptors may be involved in the etiology of
      psychosis and that 5-hydroxytryptamine2 (5-HT2) antagonists may have utility in
      treating the negative symptoms of psychosis as well as reducing the side effects
      associated with the typical antipsychotic haloperidol. We have evaluated the
      potential antipsychotic effects of 1-(cyclopropylmethyl)-4-(2'(4''-fluorophenyl)
      2'-oxoethyl)piper i din e HBr (DuP 734), a selective and potent sigma and 5-HT2
      receptor ligand with weak affinity for D2 receptors, in behavioral animal models
      that are not necessarily dependent on dopamine antagonism. DuP 734 potently
      blocked mescaline-induced scratching (ED50 = 0.35 mg/kg, p.o.) and aggressive
      activity (ED50 = 1.9 mg/kg, p.o.) and was relatively much weaker as an
      apomorphine antagonist (ED50 = 12 mg/kg, p.o.). This was in contrast to the
      typical antipsychotic agents such as haloperidol and chlorpromazine, which were
      very potent in all three tests. In rats, DuP 734 did not antagonize avoidance
      behavior or induce catalepsy, and, therefore, differed from the potent dopamine
      receptor antagonist antipsychotics. It did, however, reduce lever response rates
      in a random interval 60-sec food reward schedule of reinforcement (ED50 = 6.0
      mg/kg, p.o.) in rats. The results suggest that DuP 734 may have antipsychotic
      activity without the liability of motor side effects typical of neuroleptics.
      Although DuP 734 itself did not antagonize avoidance activity, it significantly
      enhanced the potency of haloperidol in blocking avoidance behavior by 3-fold (by
      shifting the ED50 from 0.94 to 0.36 mg/kg, p.o.), whereas the ED50 of haloperidol
      for blockade of escape behavior and induction of catalepsy was not
      affected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361572
TI  - DuP 734 [1-(cyclopropylmethyl)-4-(2'(4''-fluorophenyl)-2'-oxoethyl)- piperidine
      HBr], a sigma and 5-hydroxytryptamine2 receptor antagonist: receptor-binding,
      electrophysiological and neuropharmacological profiles.
AB  - It has been suggested that sigma receptor antagonists may be useful as
      antipsychotic drugs and that 5-hydroxytryptamine (5-HT2) receptor antagonists
      produce improvements of the negative symptoms of schizophrenia. [1
      (Cyclopropylmethyl)-4-(2'-(4''-fluorophenyl)-2'- oxoethyl)-piperidine HBr] (DuP
      734) is a novel compound with high affinity for the sigma (Ki = 10 nM) and 5-HT2
      (Ki = 15 nM) receptors, but low affinity for dopamine receptors (Ki > 1000 nM) as
      well as 33 other receptors, ion channels and second messenger systems in vitro.
      DuP 734 did not inhibit the synaptosomal uptake of dopamine, 5-HT or
      norepinephrine. Oral administration of DuP 734 potently blocked 5-hydroxy-L
      trytophan (5-HTP)-induced head twitch in the rat (ED50 = 6.5 mumol/kg),
      indicating 5-HT2 antagonist activity. Extracellular single-unit recording studies
      demonstrated that DuP 734 antagonized the effect of the selective sigma ligand
      (+)-3-(3-hydroxyphenyl-N-(1-propyl) piperidine [(+)-3-PPP] on dopamine neuronal
      activity in the substantia nigra of the rat with an ED90 of 3.6 mumol/kg i.v. The
      sigma receptor agonists (+)-SKF 10,047 and phencyclidine both elicited rotational
      behavior in rats with unilateral lesion of the substantia nigra. The rotational
      behavior induced by either (+)-SKF 10,047 or phencyclidine was dose-dependently
      antagonized by DuP 734 with oral ED50 of 8.7 and 19.6 mumol/kg, respectively. The
      5-HT2 receptor antagonist ICI 169,369, even at high doses (up to 33 mumol/kg,
      s.c.), did not antagonize the rotational behavior induced by (+)-SKF
      10,047.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361573
TI  - [3H]DuP 734 [1-(cyclopropylmethyl)-4-(2'-(4''-fluorophenyl)-2'- oxoethyl)
      piperidine HBr]: a receptor binding profile of a high-affinity novel sigma
      receptor ligand in guinea pig brain.
AB  - The in vitro binding properties of 1-(cyclopropylmethyl)-4-(2'-(4''-fluorophenyl)
      2'-oxoethyl)pipe ridi ne HBr, [3H]DuP 734, a novel sigma receptor ligand, were
      examined in homogenates of guinea pig brain. Specific [3H]DuP 734 binding (10
      microM haloperidol-displaceable) in cerebellum was dependent on pH, temperature
      and membrane protein concentration, reversible, saturable and of high affinity
      (KD = 228 +/- 34 pM; Bmax = 3856 +/- 340 fmol/mg protein). [3H]DuP 734 binding
      was substantially reduced by treating the membrane with proteases and completely
      abolished by heat denaturation. [3H]DuP 734 binding was unaffected by the
      presence of ions or guanine nucleotides. The pharmacological characteristics of
      [3H]DuP 734 binding in cerebellum displayed the same rank order and
      stereospecificity as previously reported for sigma receptors in brain. [3H]DuP
      734-labeled sigma receptors were heterogeneously distributed throughout the
      central nervous systems with highest densities present in pons/medulla,
      hypothalamus, spinal cord and cerebellum. In addition to labeling sigma
      receptors, a second, lower affinity, haloperidol-insensitive [3H] DuP 734 binding
      site was observed in the cerebral cortex. This second site could not be
      positively identified as a neuronal receptor because a series of standard
      compounds were unable to displace [3H]DuP 734 from the haloperidol-insensitive
      site; only structural analogs of DuP 734 proved effective in displacing [3H]DuP
      734 from the haloperidol-insensitive site. In summary, [3H]DuP 734 is a novel
      ligand that binds with high affinity to sigma receptors in brain.

PMID- 1361575
TI  - Characterization of 2,4,5-trihydroxyphenylalanine neurotoxicity in vitro and
      protective effects of ganglioside GM1: implications for Parkinson's disease.
AB  - The neurotoxic properties of 2,4,5-trihydroxyphenylalanine (TOPA; the 6
      hydroxylated derivative of dopa) was investigated in cultures of central neurons.
      Application of solutions of TOPA to cerebellar granule cells resulted in a
      concentration- and time-dependent neuronal death, with prolonged (24 hr) exposure
      producing a clear left-handed shift in the dose-response relationship from the
      one observed with a 60-min exposure (LD50: 4 and 29 microM, respectively). This
      toxicity was largely blocked by the non-N-methyl-D-aspartate antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione. Solutions of TOPA were also toxic to mesencephalic
      neurons after acute or chronic exposure, displaying the same leftward shift in
      LD50. This latter preparation contained a minor population of dopaminergic,
      tyrosine hydroxylase immunopositive cells which were likewise sensitive to the
      excitotoxic effects of TOPA. Neurotoxic activity of TOPA appeared to depend upon
      its oxidation in solution, as judged using chemical analysis and reducing agents.
      The monosialoganglioside GM1 was effective in protecting against
      neurodegeneration induced by brief or prolonged exposure to solutions of TOPA.
      These results suggest that an abnormal production or accumulation of TOPA or its
      oxidation product(s) might be involved in excitotoxicity directed to areas of the
      brain with dopaminergic innervation, and in other brain areas in Parkinson's
      disease patients on long-term dopa therapy. The selective action of gangliosides
      in disrupting the pathological consequences of glutamate receptor activation
      proposes their use as chemoprophylactic agents for preventing or arresting the
      neuronal losses accompanying such situations.

PMID- 1361574
TI  - Pharmacology of gamma-aminobutyric acidA receptor complex after the in vivo
      administration of the anxioselective and anticonvulsant beta-carboline derivative
      abecarnil.
AB  - In rodents, the effect of the beta-carboline derivative isopropyl-6- benzyloxy-4
      methoxymethyl-beta-carboline-3-carboxylate (abecarrnil), a new ligand for
      benzodiazepine receptors possessing anxiolytic and anticonvulsant properties, was
      evaluated on the function of central gamma-aminobutyric acid (GABA)A receptor
      complex, both in vitro and in vivo. Added in vitro to rat cortical membrane
      preparation, abecarnil increased [3H]GABA binding, enhanced muscimol-stimulated
      36Cl- uptake and reduced the binding of t-[35S]butylbicyclophosphorothionate
      ([35S]TBPS). These effects were similar to those induced by diazepam, whereas the
      partial agonist Ro 16-6028 (tert-butyl-(S)-8-bromo-11,12,13,13a-tetrahydro-9-oxo
      9H- imidazo[1,5-a]-pyrrolo-[2,1-c][1,4]benzodiazepine-1-carboxylate) showed very
      weak efficacy in these biochemical tests. After i.p. injection to rats, abecarnil
      and diazepam decreased in a time-dependent and dose-related (0.25-20 mg/kg i.p.)
      manner [35S]TBPS binding measured ex vivo in the cerebral cortex. Moreover, both
      drugs at the dose of 0.5 mg/kg antagonized completely the convulsant activity and
      the increase of [35S]TBPS binding induced by isoniazide (350 mg/kg s.c.) as well
      as the increase of [35S]TBPS binding induced by foot-shock stress. To better
      correlate the biochemical and the pharmacological effects, we studied the action
      of abecarnil on [35S]TBPS binding, exploratory motility and on isoniazid-induced
      biochemical and pharmacological effects in mice. In these animals, abecarnil
      produced a paralleled dose-dependent (0.05-1 mg/kg i.p.) reduction of both motor
      behavior and cortical [35S]TBPS binding. Moreover, 0.05 mg/kg of this beta
      carboline reduced markedly the increase of [35S]TBPS binding and the convulsions
      induced by isoniazid (200 mg/kg s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361576
TI  - Augmented sensitivity of D1-dopamine receptors in lateral but not medial striatum
      after 6-hydroxydopamine-induced lesions in the neonatal rat.
AB  - Lesioning of neonatal rats with the neurotoxin 6-hydroxydopamine (6-OHDA) reduced
      striatal dopamine (DA) levels to 3% of control levels and produced marked
      increases in the behavioral effects of the selective D1-DA receptor agonist SKF
      38393 in these animals when tested as adults. However, no differences were
      observed, either in basal or D1-DA-stimulated striatal cAMP formation or in
      forskolin-stimulated or GTP-stimulated cAMP production, between control and
      lesioned animals. C-fos-like immunoreactivity after SKF-38393 was significantly
      greater in dorsolateral vs. ventromedial aspects of the striatum in lesioned
      animals. Like the c-fos response, augmented electrophysiological responsiveness
      to SKF-38393 occurred in lesioned rats in lateral, but not medial, portions of
      the striatum. No differences were found in nucleus accumbens in sensitivity to
      SKF-38393 between control and lesioned rats. Although autoradiographic
      determination of D1-DA receptor binding throughout the striatum and nucleus
      accumbens revealed no differences between unlesioned and lesioned rats, tyrosine
      hydroxylase-like immunoreactivity was reduced with a regional distribution
      inversely related to c-fos-like immunohistochemical expression. These findings
      demonstrate that regionally enhanced electrophysiological sensitivity of striatal
      neurons to D1-DA receptor agonists after neonatal 6-OHDA-induced lesions is
      associated with regional changes in c-fos-like immunoreactivity and tyrosine
      hydroxylase-like immunohistochemistry, but not with changes in D1-DA receptor
      autoradiography or D1-DA-stimulated adenylyl cyclase activity. Such regional
      consequences of 6-OHDA-induced lesions in neonates may contribute to the unique
      behavioral patterns observed when these rats are challenged with L-dopa or D1-DA
      agonists as adults.

PMID- 1361577
TI  - Effects of intrahippocampal injections of N-methyl-D-aspartate receptor
      antagonists and scopolamine on working and reference memory assessed in rats by a
      three-panel runway task.
AB  - In order to elucidate the roles of hippocampal N-methyl-D-aspartate-type
      excitatory amino acid receptors in working and reference memory in rats, the
      effects of intrahippocampal injections of selective and competitive N-methyl-D
      aspartate receptor antagonists such as CGS 19755 (cis-4-phosphonomethyl-2
      piperidine carboxylic acid), 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic
      acid and 2-amino-5-phosphonovaleric acid on this behavior were examined with a
      three-panel runway task. The results were compared with the effect of the
      muscarinic receptor antagonist scopolamine. In the working memory task, CGS 19755
      and 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid at 10 and 32
      ng/side, injected bilaterally into the dorsal hippocampus before testing,
      produced a significant increase in the number of errors (attempts to pass through
      two incorrect panels of the three panel-gates at four choice points). This also
      occurred after the rats were given systemic injection of these drugs at 3.2 and
      10 mg/kg. In the reference memory task, neither CGS 19755 nor 3-[(+-)-2
      carboxypiperazin-4-yl]propyl-1-phosphonic acid affected the number of errors,
      whether given at doses up to 32 ng/side intrahippocampally or up to 10 mg/kg
      systemically. Working memory errors also increased significantly after
      intrahippocampal injections of d-2-amino-5-phosphonovaleric acid at 100 and 320
      ng/side, but were not affected by I-2-amino-5-phosphonovaleric acid at doses up
      to 1 microgram/side. On the other hand, intrahippocampal scopolamine at 1.0 and
      3.2 micrograms/side increased significantly working memory errors, without
      affecting reference memory errors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361579
TI  - DL-tetrazol-5-ylglycine, a highly potent NMDA agonist: its synthesis and NMDA
      receptor efficacy.
AB  - At physiological pH, the spatial arrangement of the three charges of DL-tetrazol
      5-ylglycine (5) could be viewed as similar to those found in certain
      conformations of the two excitatory amino acids (EAAs)--aspartic and glutamic
      acids. Given significant binding to one or more EAA receptors, 5 would offer
      unique modeling and perhaps biological opportunities. We have previously shown it
      to be the most potent NMDA agonist known, with a unique and marked in vitro
      neutrotoxicity at depolarizing concentrations. Now we report the details required
      for its synthesis, together with its potency and efficacy in two assays of
      functional activation of the NMDA receptor, namely agonist-influenced [3H]MK801
      binding and agonist-induced release of the neurotransmitter [3H]-norepinephrine
      from brain slices. In both these assays DL-tetrazol-5-ylglycine proved to be more
      potent and efficacious than NMDA and cis-methanoglutamate. It was more potent
      than, and equally efficacious to, L-glutamate in [3H]MK801 binding. The
      structural features of 5 may well reflect optimal agonist interaction at the NMDA
      receptor site. (We considered the possibility that some decarboxylation of DL
      tetrazol-5-ylglycine may have occurred during testing. This would give 5
      (aminomethyl)tetrazole (13), the tetrazole acid analog of glycine; and glycine is
      involved in NMDA receptor activation. Compound 13 does not affect [3H]glycine
      binding at the strychnine-insensitive glycine binding site, and [3H]MK801 binding
      studies showed that the (aminomethyl)-tetrazole, even if is formed, would
      probably have no effect on the activity of tetrazol-5-ylglycine at the NMDA
      receptor.

PMID- 1361578
TI  - Synthesis and biological characterization of alpha-(4-fluorophenyl)-4-(5-fluoro-2
      pyrimidinyl)-1-piperazinebutanol and analogues as potential atypical
      antipsychotic agents.
AB  - A series of 1-(pyrimidin-2-yl)piperazine derivatives were prepared and evaluated
      in receptor binding assays and in in vivo behavioral paradigms as potential
      atypical antipsychotic agents. Compound 16 (BMS 181100 (formerly BMY 14802))
      emerged as the lead compound from within the series on the basis of its good
      activity and duration of action in the inhibition of both conditioned avoidance
      responding and apomorphine-induced stereotopy in the rat. Compound 16 not only
      failed to induce catalepsy in the rat but was quite effective in reversing the
      cataleptic effect of neuroleptic agents, thus indicating a low propensity for
      causing extrapyramidal side effects. In comparison to reference antipsychotic
      agents, 16 appeared to be less sedating and was relatively weaker in causing
      muscle incoordination. The compound was essentially inactive in binding to
      dopamine D2 receptors and its chronic administration to rats did not result in
      dopamine receptor supersensitivity. It exhibited modest to weak affinity for 5
      HT1A and alpha 1 receptors but was found to be a fairly potent ligand for sigma
      binding sites (IC50 vs (+)-[3H]-3-PPP = 112 nM). Although the resolved
      enantiomers of racemic 16 did not show dramatic differences from racemate or from
      each other in most tests, the R(+) enantiomer was up to 11-fold more potent than
      its antipode in binding to sigma sites. Several studies have indicated that 16
      may be a limbic-selective agent which may modulate dopaminergic activity by an
      indirect mechanism. The compound has been selected for clinical evaluation in the
      treatment of psychosis.

PMID- 1361581
TI  - Computer-aided mapping of the beta-adrenoceptor. 1. Explanation for effect of
      para substitution on blocking activity at the beta-1-adrenoceptor.
AB  - Anomalously low affinities for the beta-1-adrenoceptor are seen for members of a
      series of para-substituted N-isopropylphenoxypropanolamines in which the
      substituent is able to conjugate with the aromatic ring. The energy of
      conjugation was calculated using the AM1 semiempirical molecular orbital method
      and appears to correlate with the loss of binding energy, and hence affinity for
      the receptor. This suggests that binding is associated with movement of the
      substituent out of the plane of the aromatic ring due to steric interference with
      the receptor. A previously unrecognized binding site for aromatic groups off the
      para position is also identified.

PMID- 1361580
TI  - N-terminal alkylated derivatives of [D-Pro10]dynorphin A-(1-11) are highly
      selective for kappa-opioid receptors.

PMID- 1361582
TI  - Bioisosteric replacement of the alpha-amino carboxylic acid functionality in 2
      amino-5-phosphonopentanoic acid yields unique 3,4-diamino-3-cyclobutene-1,2-dione
      containing NMDA antagonists.
AB  - In this report, a novel bioisostere of the alpha-amino acid, 3,4-diamino-3
      cyclobutene-1,2-dione, has been incorporated into a series of compounds which are
      NMDA antagonists. These compounds, which are achiral and easily prepared,
      demonstrated good affinity at the NMDA receptor by their ability to displace
      [3H]CPP binding in vitro. In particular, the phosphonic acid 24 provided
      protection against NMDA-induced lethality in mice equivalent to 2-amino-7
      phosphonoheptanoic acid (5). This was considered an encouraging result in lieu of
      the fact that 24, like 5, lacks the conformational rigidity of the more potent
      NMDA antagonists. In addition, analogs that incorporate the 1,2,4-oxadiazolidine
      3,5-dione heterocycle of quisqualic acid and the unsaturation of kainic acid were
      prepared to explore selectivity at the non-NMDA receptor subtypes.

PMID- 1361583
TI  - Helical structure of P pili from Escherichia coli. Evidence from X-ray fiber
      diffraction and scanning transmission electron microscopy.
AB  - The structure of the P pili from Escherichia coli has been studied using X-ray
      fiber diffraction and scanning transmission electron microscopy (STEM). Analysis
      of the fiber diffraction data indicates that the pili are constituted largely of
      structural subunits arranged helically with approximately 33 subunits in 10 turns
      in an axial repeat of 244.5 +/- 1.8 A. Radial electron density distributions
      calculated from equatorial diffraction data and STEM data indicate that the pili
      are about 65 A in diameter with a small central cavity roughly 15 A across. The
      principal protein component of the pili is PapA, which has a molecular weight of
      16.5 kDa. Assuming that each subunit consists of a single PapA molecule, the mass
      per-unit-length of the pili predicted from the X-ray data is 2.23 kDa/A.
      Measurements of mass-per-unit-length were also made through the analysis of STEM
      images. These measurements indicate a value of 2.13 +/- 0.14 kDa/A. STEM images
      demonstrated the presence of thin, thread-like structures emerging from the ends
      of pili and spanning breaks in the pili structure. These structures, which have
      been observed under other conditions, have been termed fibrillae. In the STEM
      images the fibrillae appear about 20 A in diameter. The mass-per-unit-length of
      the fibrillae was estimated using the STEM data to be 0.4 kDa/A. These data are
      consistent with the fibrillae representing an unwound or unraveled form of the
      pili proteins overstretched to about five times the length they would have in the
      intact pili.

PMID- 1361585
TI  - Prevalence of RAS oncogene mutation in head and neck carcinomas.
AB  - RAS genes encode for a protein (p21) known to play an important role in the
      regulation of normal signal transduction and cell growth. Activation of RAS genes
      have been strongly implicated in the pathogenesis of cancer in cell line studies,
      animal models and in human tumors. RAS genes have been shown to be mutated in 10
      to 15% of human solid tumors but the frequency of mutation varies widely
      depending on the tumor type. The prevalence of RAS mutation has not been well
      established in head and neck squamous cell carcinomas (SCC). The purpose of our
      study was to screen a relatively large number (50) SCC tumors using a gene
      amplification technique, the polymerase chain reaction (PCR). H-RAS gene mutation
      is identified by diagnostic restriction length polymorphism, created by
      introducing specific mismatched primers in the PCR. The first 20 tumors were also
      amplified and directly sequenced for K-RAS codon 12 and 13. Four of the 50
      screened tumors were positive for H-RAS codon 12 mutation. All tumor DNA screened
      normal at codon 61 and the first 20 tumors were also normal at K-RAS codon 12 and
      13. The prevalence of RAS mutations appears to be low in head and neck squamous
      cell carcinomas. Tumors positive for point mutation in the H-RAS gene revealed
      some unusual clinical characteristics.

PMID- 1361584
TI  - 3H-D-aspartate release from cerebellar granule neurons is differentially
      regulated by glutamate- and K(+)-stimulation.
AB  - Neurotransmitter release in response to either 55 mM K+ or 25 microM glutamate as
      well as its dependency on Ca2+ from different sources was compared in cultured
      glutamatergic cerebellar granule cells from rat brain. The intracellular Ca2+
      concentration was monitored at the single cell level in neurites as well as cell
      bodies employing the fluorescent Ca2+ indicator fura-2. Transmitter release was
      assayed using 3H-D-aspartate to label the exogenously accessible glutamate pools,
      which in these neurons is believed to also include the transmitter pool. In an
      attempt to distinguish whether transmitter release was dependent on an intact
      cytoskeleton or not, the colchicine-like drug Nocodazole, which also blocks
      transport of vesicles, was used. K(+)-stimulated transmitter release consisted
      for the major part (around 70%) of a Ca(2+)-dependent, Nocodazole sensitive
      release component and this K(+)-induced release appeared to be almost exclusively
      dependent on N-type Ca2+ channels. In contrast, 50% of the glutamate-induced
      Ca(2+)-dependent release was triggered by Ca2+ from a Dantrolene sensitive
      intracellular Ca2+ pool. Since these neurons undergo a pronounced maturational
      change in which neurotransmitter vesicles become increasingly prominent, the Ca2+
      responses and transmitter release evoked by the two different stimuli were
      investigated as a function of the culture period. K+ and glutamate were found to
      increase intracellular [Ca2+] differentially. In 1-day-old cultures K+ elicited a
      small albeit significant increase in [Ca2+]i while glutamate was completely
      without effect. In 7-day-old neurons both agents induced a large increase in
      [Ca2+].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361586
TI  - Measurement of proliferative index in squamous cell carcinoma by flow cytometry.
AB  - Squamous cell carcinoma of the upper aerodigestive tract presents significant
      problems in determining appropriate treatment regimens. Staging aided by
      sophisticated investigations allows for planning of treatment, but there is a
      definite need for a specific and reproducible marker to quantify biological
      aggressiveness. For some classes of tumors the DNA ploidy of cells, as determined
      by flow cytometry, has shown good correlation to pathologic grading and
      prognosis. Using a mathematical model, it is possible to calculate the S-phase
      fraction, which is indicative of proliferative activity and may reflect tumor
      aggressiveness. However, this parameter is often difficult to determine reliably
      in squamous cell carcinoma. An optimal marker would be a measureable protein
      related to proliferation. An attempt was made to use flow cytometry to measure
      the nuclear enzyme topoisomerase II to assess proliferation in cultured cell
      lines. Although the antibody was specific to the extracted protein, constituents
      of the rabbit serum bound non-specifically throughout fixed cells. Further
      purification of this antibody preparation could realize its diagnostic potential.
      Antibody against proliferating cell nuclear antigen was more specific, resulting
      in good correlation flow cytometrically with the S-phase fraction of the cultured
      cell lines. The results obtained with these protein markers deems further
      investigation into their use as prognostic indicators. The protocol has been
      established to apply this technology to tumor samples and establish a meaningful
      parameter of biological behavior of tumors, upon which treatment regimens can be
      confidently based.

PMID- 1361587
TI  - [Sequential extra-anatomical shunting in the Leriche-Takayasu syndrome].

PMID- 1361588
TI  - Intermediate Biomarkers of Precancer and their Application in Chemoprevention.
      Workshop. Keystone, Colorado, October 3-7, 1991.

PMID- 1361591
TI  - [Modern computer technology in medical decision making stimulates interest in
      intuition].

PMID- 1361589
TI  - Aberrant crypts in human colonic mucosa: putative preneoplastic lesions.
AB  - Aberrant crypts are recognized in methylene blue-stained, unsectioned, colonic
      mucosa by their increased size, elliptical lumenal opening, thicker epithelial
      layer, and increased pericryptal region. Aberrant crypt foci in rodents are
      observed as early as 2 weeks and for at least 9 months after a single dose of
      carcinogen, have a distribution that parallels that of tumors, and have an
      increased number of aberrant crypts per focus with time after the carcinogen
      dose. The ability to quantify these lesions in the entire colon of rodents in
      less than an hour suggests that aberrant crypts may provide a highly efficient in
      vivo bioassay for colon carcinogens. Since aberrant crypt foci appear to be the
      earliest identifiable putative precursors of colon cancer, they represent lesions
      that can be characterized further for the earliest genetic and biochemical
      alterations. In F344 rats, we have demonstrated that aberrant crypts have
      multiple histochemically-detectable enzyme alterations. Using similar techniques,
      we were the first to demonstrate aberrant crypts in unsectioned human mucosa.
      After embedding and sectioning, these microscopic aberrant crypts resemble rare
      lesions described earlier in the literature after extensive serial sectioning. In
      rats and humans, aberrant crypts may be histologically normal or display varying
      degrees of dysplasia and histochemically-detectable altered enzyme activities.
      These putative, preneoplastic lesions should reveal early changes that precede
      colon cancer and ways to alter their progression.

PMID- 1361590
TI  - Effect of psychotropic drugs on histamine H2-receptors in rat isolated uterus.
AB  - The effects of the monoamine oxidase inhibitors iproniazid, nialamide and
      phenelzine, the neuroleptics haloperidol and thioridazine, and the
      benzodiazepines diazepam and clonazepam on histamine H2-receptors were assessed
      on rat isolated uterus. The monoamine oxidase inhibitors showed a slight non
      competitive antihistamine H2 activity, while diazepam and clonazepam were devoid
      of any action. Haloperidol and thioridazine inhibited in a dose-dependent manner
      the tonic component of KCl induced contraction, while thioridazine under the same
      conditions exhibited a slight antihistamine H2 activity. These data show that the
      drugs tested are devoid of or elicited only a slight antihistamine H2 activity at
      high non-therapeutic concentrations.

PMID- 1361592
TI  - [GT is superior as a marker of alcohol abuse].

PMID- 1361593
TI  - [Perception during anesthesia--monitoring of the depth of anesthesia will be soon
      possible].

PMID- 1361594
TI  - Comparison of oral-steroid sparing by high-dose and low-dose inhaled steroid in
      maintenance treatment of severe asthma.
AB  - It is not clear whether high doses of inhaled steroids have a greater sparing
      effect than low doses on the requirement for systemic steroids. In a randomised,
      double-blind, multicentre study, we compared the effects of high-dose (1500
      micrograms/day) and low-dose (300 micrograms/day) inhaled beclomethasone
      dipropionate (BDP) in patients with severe asthma requiring a daily oral
      prednisolone dose of 10-40 mg. During a 3-month run-in period, we tried to
      achieve optimum asthma control by means of oral steroid and inhaled BDP 300
      micrograms/day. The patients were then allocated to high-dose (n = 71) or low
      dose (n = 72) treatment by an independent observer who took into account various
      prognostic factors. BDP was administered by means of an aerosol inhaler with a
      spacer device. The dose of systemic steroid was reduced as much as possible
      during the 6-month study period while keeping the peak expiratory flow (PEF)
      constant and asthma clinically stable. There was no difference between the low
      dose and high-dose treatment groups in the mean reduction in oral prednisolone
      dose achieved by the end of the study (5.2[ SD 7.9] vs 5.0 [9.4] mg/day). The
      maximum response to inhaled steroid was seen, however, only after several months'
      therapy in both groups. There were no differences between the groups in use of on
      demand beta-agonist inhalations or in asthma symptoms, and PEF values were
      constant throughout the study. Both doses of BDP were well tolerated. High doses
      of inhaled steroid offer no further benefit over low doses in the maintenance
      treatment of severe steroid-dependent asthma when the inhaled steroid is
      administered with a spacer device.

PMID- 1361596
TI  - Comparison of saliva and serum for HIV surveillance in developing countries.
AB  - Saliva has been proposed as a non-invasive alternative to serum for HIV antibody
      testing. In a field study in Myanmar (formerly Burma), we evaluated such an
      alternative to identify the frequency of HIV infection in a surveillance
      programme of high-risk and low-risk sentinel groups. Duplicate vials of saliva
      and serum were collected from 479 high-risk and 1039 low-risk subjects. One vial
      of each pair was analysed blind in two laboratories, one in the USA and the other
      in Myanmar. The US laboratory followed WHO confirmatory strategy III with three
      different enzyme-linked immunosorbent assays (ELISAs), while the laboratory in
      Myanmar followed strategy I with one ELISA. Serum testing in the US was the gold
      standard. The Cambridge ELISA with saliva was a more effective surveillance tool
      (sensitivity 90.5%, specificity 99.5-100%) for describing the frequency of
      subjects with HIV antibodies than the serum ELISA supplied to Myanmar by WHO
      (95.9% and 98.3%, respectively). Saliva is recommended as a safe and effective
      alternative to serum for HIV antibody testing with ELISA in surveillance
      programmes in developing countries.

PMID- 1361595
TI  - Bone turnover in malnourished children.
AB  - Pyridinoline (PYD) and deoxypyridinoline (DPD) are cross-linking aminoacids of
      collagen that are located mainly in bone and cartilage. When bone matrix is
      resorbed these cross-links are quantitatively excreted in the urine and therefore
      represent specific markers. We have measured the urinary excretion rate of PYD
      and DPD in 46 severely malnourished boys to assess their skeletal turnover and to
      relate this to their subsequent rate of growth. The children were aged 13 months
      (SD 6), and height-for-age was -3.6 (1.6) Z-score, and weight-for-height was -2.4
      (0.8) Z-score. PYD excretion when malnourished and after "recovery" was 11.2
      (4.6) nmol h-1m-2 and 32.2 (10.8) nmol h-1m-2 and DPD excretion was 2.6 (1.3)
      nmol h-1m-2 and 7.5 (3.0) nmol h-1m-2, respectively. The ratio of the two cross
      links did not change with recovery. These data show that cartilage and bone
      turnover is much lower in the malnourished than in the recovered child. There was
      no difference in the degree of depression of turnover between the children with
      marasmus, marasmic-kwashiorkor, or kwashiorkor. The rate of height gain during
      recovery was significantly related to cross-link excretion, age, and weight-for
      height on admission. These three factors accounted for 44% of the variance in the
      height velocity of the children. PYD and DPD excretion rate could be used to
      assess therapeutic interventions designed to alleviate stunting.

PMID- 1361597
TI  - Lipoprotein(a) and accelerated coronary artery disease in cardiac transplant
      recipients.
AB  - High concentrations of serum lipoprotein(a) (Lp(a)) are associated with an
      increased risk of atherosclerotic vascular disease in the nontransplanted
      population. However, its relation with accelerated coronary artery disease (CAD)
      in cardiac transplant recipients has not been reported. We measured serum Lp(a)
      in 130 cardiac transplant recipients undergoing routine follow-up, which included
      annual coronary angiography. The median Lp(a) concentration in 33 patients with
      CAD was 71 mg/dl, which was significantly higher than the corresponding value of
      22 mg/dL in the 97 patients without CAD (p = 0.0006). Multivariant analysis
      showed the serum Lp(a) value to be a higher significant risk factor for CAD
      irrespective of the other factors included in the regression analysis. Thus a
      high concentration of serum Lp(a) is an important, independent risk factor for
      the development of accelerated CAD in transplant recipients.

PMID- 1361598
TI  - Recognition of pneumonia by primary health care workers in Swaziland with a
      simple clinical algorithm.
AB  - In developing countries primary health care workers are being trained to manage
      and treat acute respiratory infections with a protocol developed by the WHO. We
      tested the ability of nurses and nursing assistants in Swaziland to recognise the
      signs and symptoms of pneumonia; with the results of a paediatrician's
      examination as "gold standard", sensitivities and specificities were calculated.
      Danger signs of stridor and abnormal sleepiness were poorly recognised
      (sensitivity 0-50%) by the health care workers, as was audible wheeze. Severe
      undernutrition, tachypnoea, and chest wall indrawing were well recognised.
      Overall, the recognition of pneumonia was good (sensitivity 71-83%, specificity
      84-85%). These findings highlight topics for emphasis in training.

PMID- 1361599
TI  - Fine-needle extrathoracic lymph-node aspiration in HIV-associated sputum-negative
      tuberculosis.
AB  - HIV-associated tuberculosis is increasingly seen in Zimbabwe and other developing
      countries. The clinical and radiological features are often atypical, and
      diagnostic confusion may arise when sputum smears are negative. Patients with
      suspected intrathoracic tuberculosis frequently have palpable extrathoracic lymph
      nodes. In this study, Ziehl-Neelsen staining of aspirates from extrathoracic
      lymph nodes revealed acid-fast bacilli in 20 (71%) of 28 patients with suspected
      tuberculosis, and 20 (87%) of 23 patients in whom a final diagnosis of
      tuberculosis was made Aspiration is simple, rapid, and cheap and may be of value
      in the diagnosis of tuberculosis, especially in developing countries with limited
      diagnostic and therapeutic resources.

PMID- 1361600
TI  - Oral and gastrointestinal manifestations of epidermolysis bullosa.
AB  - The mouth, oesophagus, and anus are often involved in dystrophic and junctional
      epidermolysis bullosa, but the frequency is unknown. Among 246 patients with
      epidermolysis bullosa, dysphagia developed in 76% of those with recessive
      dystrophic, in 20% of those with dominant dystrophic, in 15% of those with
      junctional, and in 2% of those with simplex forms. Lingual adhesions or
      microstomia occurred in dystrophic epidermolysis bullosa only, but were eight
      times more common in recessive than in dominant subtypes. These lesions are
      provoked by the trauma of eating and further reduce food intake, which
      exacerbates constipation caused by anal blisters and results in malnutrition.
      Management requires specialised multidisciplinary care.

PMID- 1361601
TI  - Nifedipine: a new life with GITS?

PMID- 1361602
TI  - Botulinum toxin.

PMID- 1361603
TI  - Mechanical coronary atherectomy.

PMID- 1361604
TI  - Multiple endocrine neoplasia type 2: awaiting the gene.

PMID- 1361605
TI  - Bioelectrical impedance and body composition.

PMID- 1361606
TI  - The molecular pathogenesis of Alzheimer's disease: clinical prospects.

PMID- 1361608
TI  - The extent of man from Vitruvius to Marfan.
AB  - It is frequently stated that patients with Marfan's syndrome have an arm span
      greater than height. This implies a characteristic different from the proportions
      in normal adult man, in whom span and height are often thought to be equal. Such
      equality of span and height, which allows man to be portrayed within a square,
      has been a widely held concept, immortalised by Leonardo da Vinci, that dates
      from the Roman Vitruvius. However, in the past two hundred years, anthropometry
      has shown that span exceeds height in 59-78% of normal adult white men. Thus not
      only is the classic concept of equality of span and height generally incorrect,
      but also a span greater than height cannot be considered characteristic of
      Marfan's syndrome. Paradoxically, in some affected individuals, Vitruvian
      equality of height and span may occur.

PMID- 1361609
TI  - Krook's dyslexia.

PMID- 1361607
TI  - Red blood cell transfusion in warm-type autoimmune haemolytic anaemia.
AB  - Blood transfusions are regarded as hazardous in patients with warm-type
      autoimmune haemolytic anaemia (AIHA) because of potential intensification of
      haemolysis and a presumed high incidence of alloimmunisation. We have
      retrospectively analysed data of 79 multitransfused patients (74 adults, 5
      children) with detectable warm autoantibodies and transitory or persisting
      haemolytic anaemia. All patients had received blood transfusions on at least two
      occasions. Patients were reexamined at least twice within the first 6 months of
      transfusion (duration of follow-up 6 months-12 years). 53 patients had received
      blood transfusions because of decompensated AIHA, all of whom presented with
      detectable autoantibodies against red blood cells. None of these patients had
      transfusion-related alloimmunisation or a definite increase in haemolysis, even
      when the transfused red cells were serologically incompatible because of free
      serum autoantibodies. The other 26 patients had no signs of AIHA at presentation
      (negative direct and indirect antiglobulin test), but received blood transfusions
      for anaemia due to various other causes. 23 of these 26 patients went on to
      develop alloantibodies as well as autoantibodies upon transfusion, and 3 patients
      developed autoantibodies alone. Our findings do not support the generally
      accepted notion that transfusion therapy should be avoided in AIHA patients.
      Rather, they indicate that the incidence of alloimmunisation as well as adverse
      haemolytic transfusion reactions are less common in AIHA patients than in other
      multitransfused patients.

PMID- 1361610
TI  - Curbing the drugs bill.

PMID- 1361611
TI  - France: nosocomial multidrug-resistant TB.

PMID- 1361612
TI  - India: disquiet about AIDS control.

PMID- 1361614
TI  - Mammography.

PMID- 1361615
TI  - Mammography.

PMID- 1361617
TI  - Mammography.

PMID- 1361616
TI  - Mammography.

PMID- 1361618
TI  - DON'T PANIC with ocular motor palsies.

PMID- 1361619
TI  - Psychotropic drugs and myocardial infarction.

PMID- 1361620
TI  - Rapid HIV tests: two for the price of one.

PMID- 1361621
TI  - Reliability of western blotting for the confirmation of HIV-1 seroconversion.

PMID- 1361622
TI  - Xerostomia associated with didanosine.

PMID- 1361624
TI  - Is cervical cancer monoclonal?

PMID- 1361623
TI  - In-vitro activity of zidovudine against mycoplasma.

PMID- 1361625
TI  - Serum interleukin 10 in early stage multiple myeloma.

PMID- 1361627
TI  - Doctors to be.

PMID- 1361626
TI  - Inhaled nitric oxide for postoperative pulmonary hypertension in patients with
      congenital heart defects.

PMID- 1361628
TI  - Management of persistent vegetative state.

PMID- 1361629
TI  - Meaning of human sexual intercourse.

PMID- 1361630
TI  - A right to reproduce?

PMID- 1361631
TI  - Familial adenomatous polyposis and genomic imprinting.

PMID- 1361632
TI  - Is a change in rabies vaccine schedule necessary for travellers?

PMID- 1361633
TI  - ACE inhibitors for myocardial infarction and unstable angina.

PMID- 1361634
TI  - ACE inhibitors for myocardial infarction and unstable angina.

PMID- 1361635
TI  - ACE inhibitors for myocardial infarction and unstable angina.

PMID- 1361636
TI  - ACE inhibitors for myocardial infarction and unstable angina.

PMID- 1361637
TI  - Cholera in young children in an endemic area.

PMID- 1361638
TI  - Long seronegative window in schistosoma infection.

PMID- 1361639
TI  - Nocturnal enuresis.

PMID- 1361640
TI  - Prevention of breast cancer.

PMID- 1361641
TI  - Prevention of breast cancer.

PMID- 1361642
TI  - Prevention of breast cancer.

PMID- 1361643
TI  - Prevention of breast cancer.

PMID- 1361644
TI  - Rigors and bronchospasm with urokinase after streptokinase.

PMID- 1361645
TI  - Erwinase-induced pancreatitis.

PMID- 1361646
TI  - Minocycline-related lupus.

PMID- 1361647
TI  - Long follow-up of tuberous sclerosis treated with vigabatrin.

PMID- 1361648
TI  - Nitric oxide and cerebral malaria.

PMID- 1361649
TI  - [Multidisciplinary Approach to Infections of the Central Nervous System in
      Pediatrics. Genova, 5-6 November 1992].

PMID- 1361650
TI  - [Intracranial bacterial abscess and empyema].

PMID- 1361651
TI  - The Minnesota Advance Psychiatric Directive. Protecting patient decision making.

PMID- 1361652
TI  - 1993 revised classification system for HIV infection and expanded surveillance
      case definition for AIDS among adolescents and adults.
AB  - CDC has revised the classification system for HIV infection to emphasize the
      clinical importance of the CD4+ T-lymphocyte count in the categorization of HIV
      related clinical conditions. This classification system replaces the system
      published by CDC in 1986 (1) and is primarily intended for use in public health
      practice. Consistent with the 1993 revised classification system, CDC has also
      expanded the AIDS surveillance case definition to include all HIV-infected
      persons who have < 200 CD4+ T-lymphocytes/microL, or a CD4+ T-lymphocyte
      percentage of total lymphocytes of < 14. This expansion includes the addition of
      three clinical conditions--pulmonary tuberculosis, recurrent pneumonia, and
      invasive cervical cancer--and retains the 23 clinical conditions in the AIDS
      surveillance case definition published in 1987 (2); it is to be used by all
      states for AIDS case reporting effective January 1, 1993.

PMID- 1361653
TI  - [Comparison of long-term results of surgical and nonsurgical therapy in acute
      aortic dissection].
AB  - The early and long-term results of both surgical and nonsurgical therapy for 160
      patients with acute aortic dissection in our institution were analyzed. Of the 83
      patients with acute type A aortic dissection, 47 received surgery during acute
      stage, 10 received it in the chronic stage, and 26 received nonsurgical therapy.
      Of the 77 patients with acute type B aortic dissection, 27 received surgery
      during acute stage, 22 received it in the chronic stage, and 28 received
      nonsurgical therapy. Ten-year survival rates for patients receiving surgery
      during the acute stage were 62% for type A and 64% for type B dissection. This
      survival rate for type A patients was significantly higher than that for type A
      patients not receiving surgery, but the corresponding difference for type B
      patients was not significant. Present data indicate that immediate surgical
      intervention is indicated in patients with acute type A dissection, and elective
      operation in the subacute stage in patient with uncomplicated type B dissection
      following medical therapy in the acute stage.

PMID- 1361654
TI  - [Problems in ulcer surgery after the introduction of H2-receptor antagonists].
AB  - Recently, antisecretory drugs such as H2-receptor antagonists (H2-RA) or proton
      pump inhibitor have been used for peptic ulcer patients widely in Japan. However,
      there are possibilities that long term administration of H2-RA might cause
      changes in intragastric environment. The present study was designed to clarify
      the changes of surgical treatment in Japan Surgical Society training hospitals,
      before and after introduction of H2-RA. Serum gastrin and antral G-cell number
      was measured after administration of H2-RA (1 mg/kg 14 days continuous infusion)
      in rat. Also, acid secretion and gastrin response stimulated by adrenalin (40
      ng/kg.min) were measured in duodenal ulcer patients. 1) In the view of surgical
      treatment, elective operation highly decreased after the introduction of H2
      receptor antagonists, and showed the increase of the rate of emergency operation
      up to 70%. 2) Hypergastrinemia and antral G cell hyperplasia were observed after
      administration of H2-RA in rats. 3) Acid secretion stimulated by adrenalin which
      is considered as antral G cell dependent, showed a higher response in H2-RA
      treated cases than in those untreated. 4) Antrectomy was carried out in 43.4% of
      the patients treated with H2-RA versus 18.9% to the patients untreated.

PMID- 1361655
TI  - [Effect of gastric mucosal denervation on gastric carcinogenesis].
AB  - Numerous nerve fibers containing various neuropeptides are found in gastric
      mucosa. They play an important role not only in regulation of gastric secretion,
      motility and microcirculation but also in regeneration and differentiation of
      gastric mucosa. These nerve fibers are reduced in chronic atrophic gastritis
      which is considered a lesion closely related to carcinogenesis. We investigated
      the effect of gastric gastric mucosal denervation (vagotomy) on gastric
      carcinogenesis by using two experimental rat models in which chronic atrophic
      gastritis is induced by duodenogastric reflux. At first, following administration
      of MNNG, vagotomy with duodenogastric reflux enhanced gastric carcinogenesis
      compared to reflux only. At second, in the model of gastric remnant in which no
      carcinogenic agent was given, both B-I and B-II gastrectomy with vagotomy showed
      an increase of carcinoma and/or adenoma at the anastomotic site compared to those
      without vagotomy. Moreover, in vagotomized groups, there were an increase of
      labeling index of PCNA positive cells in gastric mucosa and a marked reduction of
      intramucosal neutral mucin in PAS-Alcian blue staining. These results indicate
      that the lack of gastric mucosal innervation not only induces the decrease of
      gastric mucosal cell function and cytoprotection but also enhances the increase
      of immature cell regeneration.

PMID- 1361656
TI  - [Mutations of ras and p53 genes in human non-small cell lung cancer cell lines
      and their clinical significance].
AB  - We examined 77 non-small cell lung cancer (NSCLC) cell lines for mutations of 3
      ras genes and p53 gene, and ras mutations were detected by designed RFLP assay
      generated by mismatched primers during the PCR step and p53 gene mutations were
      detected using SSCP analysis. The incidence of ras mutations were 27/77 (35%)
      while that of p53 gene mutations were 57/77 (74%). The incidence of ras mutations
      in cell lines with p53 mutations were not different from that without p53
      mutations, suggesting that they occurred independently. Neither ras nor p53
      mutations correlated with histologic subtype, disease extent, in vitro culture
      time nor prior therapy status. The patients whose cell lines had any ras
      mutations survived for shorter period of time not only among the patients who
      were treated with curative intent but among those treated with palliative
      treatment. The Cox proportional hazards model predicted the higher risk for
      patients with ras mutations but not those with p53 mutations. We conclude that
      ras and p53 mutations are frequent, apparently independent genetic alterations
      which play different roles in NSCLC and that this information should be utilized
      in surgical oncology in the near future.

PMID- 1361657
TI  - [Problems in multidisciplinary treatment from the standpoint of clinical
      characteristics in human cancers].
AB  - We investigated the amplification and expression of oncogenes in human gastric
      and breast cancers. The biological malignancy of the cases with oncogene
      amplification/expression was higher than that of the cases without
      amplification/expression. Moreover, the case with amplification/expression of
      oncogene was found to be highly correlated with distant organ metastasis. In
      strongly suggests the necessity of postoperative adjuvant therapy. In addition,
      these data will have to be taken into consideration as deciding on the way of
      operation and therapy.

PMID- 1361658
TI  - [Evaluation of immunoreactivity to erbB-2 protein as a marker of prognosis in
      bile duct carcinoma].
AB  - Recent studies of erbB-2 expression have shown that the erbB-2 oncoprotein
      correlated with poor prognosis of patients with breast cancer. Surgical treatment
      of the bile duct carcinoma is currently unsatisfactory. To evaluate erbB-2
      oncoprotein as a marker of prognosis, we analyzed 68 bile duct carcinomas
      immunohistologically, using monoclonal antibody against erbB-2 oncoprotein, as
      well as clinicopathological data and outcome. High incidence of expression of
      erbB-2 oncoprotein was shown in bile duct carcinoma. Positive rates of erbB-2
      oncoprotein correlated with stage of bile duct carcinoma. Survival of patients
      with erbB-2 expression cancer was shorter than those without erbB-2 expression
      cancer and erbB-2 expression has a prognostic value in bile duct carcinoma.

PMID- 1361659
TI  - [Pathophysiology and management of patients with diabetes mellitus in
      gastrointestinal surgery, with special reference to hepatectomy and
      pancreaticoduodenectomy].
AB  - In the 235 patients with hepatectomy, 111 with pancreaticoduodenectomy (PD) and
      547 with gastrectomy for the past 15 years and 5 months, we compared the
      incidence of postoperative complications between patients with diabetes mellitus
      (DM) and those without DM, and studied glucose metabolism and management of
      diabetic patients. DM was most frequently found at 27.7% in hepatectomy,
      especially 38.7% in cirrhotic patients, followed by 24.3% in PD and only 5.9% in
      gastrectomy. The incidence of postoperative complications was not different
      between DM and non-DM after gastrectomy and PD. It was significantly higher in DM
      than in non-DM after hepatectomy (38.5% vs. 11.8%), although there was no
      statistically significant difference in the cirrhotic patients with hepatectomy
      (34.9% vs. 23.5%). The studies on insulin metabolism preoperatively determined by
      oral glucose tolerance test and postoperative control of DM revealed that
      diabetic patients with hepatectomy, especially hepatogenous DM, had a
      significantly reduced insulin uptake in the liver and exogenous insulin
      resistance to glucose. After PD for diabetic patients, a long-term care of
      impaired pancreatic exocrine and endocrine functions was considered to be
      required, especially paying attention to lipid and zinc metabolism.

PMID- 1361660
TI  - Interactions of neurotransmitters with drugs and behavior.

PMID- 1361661
TI  - Characterization of soluble platelet guanylyl cyclase with peptide antibodies.
AB  - Soluble guanylyl cyclase partially purified from bovine and human platelets was
      characterized with antibodies raised against synthetic peptides corresponding to
      different sequences of the alpha 1- and beta 1-subunits of the bovine lung
      enzyme. On immunoblots, the platelet guanylyl cyclase was recognized by the four
      antisera used, with the exception of an antiserum against the C-terminus of the
      beta 1-subunit which did not react with the human platelet but with the bovine
      platelet beta 1-subunit. Furthermore the human platelet beta 1-subunit exhibited
      a slightly lower molecular mass than the bovine protein. The C-terminal
      antibodies precipitated native platelet and lung guanylyl cyclase activity. In
      contrast an antibody against a peptide out of the putative catalytic domain,
      which is highly conserved between all guanylyl cyclases sequenced so far, did not
      precipitate native guanylyl cyclase, although it recognized both subunits on
      immunoblots, suggesting that the respective amino acid sequence is located in an
      inner site of the protein.

PMID- 1361662
TI  - [Pathophysiology and therapy of malignant neuroleptic syndrome].
AB  - Rigidity, hyperthermia, and elevated levels of creatine phosphokinase are the
      essential features of "neuroleptic malignant syndrome" (NMS), a clinical
      condition caused either by pharmacological treatment with dopamine receptor
      antagonists or by the withdrawal of dopamine receptor agonists. An acute
      dopaminergic transmission block in the basal ganglia and the hypothalamus is
      thought to be the pathophysiological mechanism of NMS. NMS, the "malignant
      dopamine depletion syndrome", and the akinetic Parkinsonian crisis may be
      considered identical conditions with regard to their presumptive pathogenesis.
      Centrally acting dopamine receptor agonists and the peripheral calcium
      antagonist, dantrolene, are the most common adjunctive pharmacological approaches
      to NMS, although their efficacy has been questioned. The motor symptoms and the
      autonomic nervous system disturbances of NMS may be related to a relative
      glutamatergic transmission excess, as a consequence of a dopaminergic block.
      Therefore, we recommend the application of N-methyl-D-aspartate (NMDA) receptor
      antagonists such as amantadine or memantine for the management of NMS. These
      drugs counteract excitatory amino acid neurotransmission and exhibit hypothermic
      and central muscle relaxant properties. However, identification and reversal of
      the causative event, such as neuroleptic drug therapy or change of anti
      parkinsonian medication, remain the cornerstones for reducing the incidence and
      mortality of NMS.

PMID- 1361663
TI  - Sulphasalazine-induced eosinophilic pneumonia.
AB  - Eosinophilic pneumonia and skin rash developed in a 21-yr-old man while taking
      sulphasalazine. After discontinuation of the drug and treatment with steroids the
      pulmonary infiltrates and rash resolved completely. A short review of the
      literature concerning sulphasalazine-induced lung disease is presented.

PMID- 1361664
TI  - Gastroenterological Aspects of Cystic Fibrosis. Symposium proceedings. The Hague,
      The Netherlands, 10 April 1992.
AB  - Cystic fibrosis (CF) is the most common hereditary disease amongst Caucasians
      with a potentially lethal outcome. The basic defect is a dysregulation of the
      chloride channels leading to a relative dehydration of the luminal surface of the
      exocrine cells. The prognosis of CF patients is predominantly related to the
      progression of their pulmonary disease. This prognosis has improved dramatically
      during the last decennia and many patients live into adulthood. Gastrointestinal
      disturbances and, consequently, malabsorption of nutrients represent a major
      therapeutic problem in CF. A better understanding of the nutritional problems,
      including the treatment of pancreatic insufficiency, appears to contribute to an
      improved prognosis. However, the nutritional status of many patients is still
      poor and studies to optimise treatment are of paramount importance. In addition,
      with the increased life span, hepatobiliary complications will contribute to the
      morbidity of these patients and preventive treatment may be warranted. The aim of
      this Symposium was to improve our knowledge in this important field by
      considering the interesting and up-to-date contributions of many experts.

PMID- 1361665
TI  - Protein kinase C and dopamine transport--1. Effects of amphetamine in vivo.
AB  - Rats, injected with small doses of amphetamine (0.03-0.1 mg/kg, i.p.), showed an
      increase in the soluble and a decrease in the activity of the particulate protein
      kinase C (PKC) in the striatum, while large doses of amphetamine (0.3-1.0 mg/kg)
      had the opposite effect of decreasing the soluble and increasing the particulate
      activity of PKC. These effects were manifested as a change in the Km for calcium,
      without an alteration in the Vmax. They were attenuated by pretreatment with
      benztropine, a dopamine (DA) uptake blocker and by alpha-methyl-p-tyrosine (alpha
      MT), a DA synthesis inhibitor. The effects of 0.1 mg/kg amphetamine were
      insensitive to pretreatment with reserpine but were attenuated by the DA
      antagonists, SCH 23390 or sulpiride. These results suggest that the changes in
      activity of PKC induced by a small dose of amphetamine were mediated by an
      activation of DA autoreceptors, through an increase in the biophase concentration
      of DA at the synapse. In contrast, the effects of 1.0 mg/kg amphetamine on
      activity of PKC were attenuated by reserpine and by the DA agonists, LY 171555 or
      SKF 38393. They were, furthermore, potentiated by simultaneous treatment with
      sulpiride, which indicates that the two drugs act by different mechanisms. These
      results suggest that larger doses of amphetamine altered the activity of PKC at
      the DA transport site.

PMID- 1361666
TI  - Protein kinase C and dopamine transport--2. Effects of amphetamine in vitro.
AB  - Synaptoneurosomes, incubated with amphetamine, showed a biphasic dose-response
      change in activity of PKC and release of DA. Activity of particulate PKC activity
      and release of DA were decreased at 0.01-10.00 nM, while activity of both was
      increased at 1-10 microM. The effects of 0.1 nM amphetamine were attenuated by
      pretreatment with N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), a
      peptide-coupling agent which inactivated DA receptors. They persisted if the
      autoreceptors were protected with sulpiride or apomorphine (0.05 mg/kg), prior to
      the treatment with EEDQ. In these protected rats, the amphetamine-induced change
      in activity of PKC was attenuated by sulpiride. In contrast, the effects of the
      larger doses of amphetamine on the activity of PKC were not affected by
      pretreatment with EEDQ. Subcellular fractionation of tissues, incubated with 1
      microM amphetamine, showed an increase in activity of particulate PKC, only in
      the synaptic plasma membrane fraction, while tissues incubated with reserpine
      showed a decrease in activity of particulate PKC, only in the vesicular fraction.
      Similar results were seen when synaptic plasma membrane or synaptic vesicles were
      incubated directly with amphetamine or reserpine. These findings suggest the
      presence of multiple metabolic pools of PKC: a reserpine-sensitive pool, present
      in synaptic vesicles and an amphetamine-sensitive pool, present in the synaptic
      plasma membrane. That the latter pool of PKC may be involved in the transport of
      DA was indicated by the good correlation between the ability of drugs to inhibit
      the activity of PKC and their ability to inhibit the amphetamine-induced release
      of DA.

PMID- 1361667
TI  - Caroverine depresses the activity of cochlear glutamate receptors in guinea pigs:
      in vivo model for drug-induced neuroprotection?
AB  - With the aid of microiontophoretic techniques the action of caroverine, a
      quinoxaline-derivative, was tested on the receptor-linked depolarisation of the
      subsynaptic membrane of cochlear afferents. This membrane can be depolarised by
      the afferent transmitter agonist glutamate, mediated by NMDA and non-NMDA
      receptors and by acetylcholine, one of the different transmitter substances,
      released physiologically on axodendritic efferent synapses. Caroverine
      antagonized the membrane response to glutamate in an enduring but reversible
      manner. In contrast, the drug exhibited no effect on the depolarising action of
      acetylcholine. Therefore, the pharmacological profile of caroverine corresponded
      to the action of selective glutamate receptor antagonists. Since glutamate is
      likely to be the major mediator of neurotoxicity in the central nervous system,
      the selective glutamate-antagonism of caroverine is of particular interest, due
      to its putative neuroprotective competence. Caroverine is currently available
      clinically in some countries as a spasmolytic drug. Following these results it is
      proposed to test the drug for clinical efficacy in putatively glutamate-induced,
      excitotoxic disorders of the brain.

PMID- 1361668
TI  - Nicotinic activity in the interpeduncular nucleus of the midbrain prolongs
      recovery from halothane anesthesia.
AB  - The influence of nicotinic transmission in the interpeduncular nucleus of the
      ventral midbrain on recovery from general anesthesia (3% halothane in oxygen) was
      assessed in rats. Immediately upon withdrawal of the anesthetic, nicotine (2
      microliters, 10(-5) to 10(-1) M) was injected into the interpeduncular nucleus.
      Larger doses of nicotine (10(-2) and 10(-1) M) significantly (P < 0.05) prolonged
      the recovery of righting reflexes (to 371 +/- 55 and 362 +/- 67 sec,
      respectively, mean +/- SE), compared with injection of saline (187 +/- 19 sec).
      Prior intramuscular administration of the nicotinic antagonist, mecamylamine (2
      mg/kg) significantly reduced the effect of 10(-2) M nicotine (to 211 +/- 43 sec).
      Injection of the nicotinic antagonist, hexamethonium (10(-1) M) led to a low mean
      recovery time (181 +/- 21 sec), not significantly different from control.
      Prolongation of recovery by 10(-2) M nicotine was not found to be significant
      when sites more dorsal to the interpeduncular nucleus were injected. An observed
      tendency for injection of nicotine to slow the post-anesthesia rate of breathing
      was not statistically significant and not correlated anatomically with the
      injection site in the midbrain. Increased release of acetylcholine has been shown
      previously to occur in the interpeduncular nucleus during anesthesia. The present
      results suggest that nicotinic activation of the interpeduncular nucleus
      facilitates or sums with the mechanisms in the brain that produce anesthesia
      under halothane.

PMID- 1361669
TI  - Bethanechol-induced responses in mudpuppy parasympathetic neurons.
AB  - The effect of bethanechol on membrane potential and excitability was determined
      in mudpuppy parasympathetic postganglionic neurons. Bethanechol induced a large
      amplitude hyperpolarization, which was followed by a smaller amplitude
      depolarization, in 115 out of 135 cells tested. In approximately 20% of these
      cells, a brief depolarization preceded the hyperpolarization. During the
      bethanechol-induced hyperpolarization, the membrane input resistance decreased
      markedly, whereas the input resistance was increased during the subsequent
      depolarization. The hyperpolarization and depolarization were blocked by atropine
      and were unaffected by d-tubocurarine, thus, both appeared to be mediated by
      muscarinic receptors. The bethanechol-induced hyperpolarization was inhibited by
      the M2 muscarinic receptor antagonist AF-DX 116, whereas the bethanechol-induced
      depolarization was unaffected. Both a nonselective increase in membrane
      conductance and a decrease in membrane potassium conductance appeared to be
      involved in the generation of the bethanechol-induced depolarization. Evidence
      for the first mechanism was obtained in barium-treated cells in which bethanechol
      initiated a rapid onset depolarization, which was reversed at membrane potentials
      near 0 mV. Evidence for the second mechanism was obtained when the
      hyperpolarization was inhibited by AF-DX 116. In AF-DX 116-treated cells, the
      membrane input resistance was increased during most of the bethanechol-induced
      depolarization. Mudpuppy neurons initiate repetitive action potential activity in
      response to long depolarizing current pulses. Following application of
      bethanechol, with the hyperpolarization negated electrotonically, the number of
      action potentials produced by a depolarizing current pulse was greater than that
      produced prior to application of bethanechol. It is suggested that activation of
      muscarinic receptors on mudpuppy cardiac neurons influences multiple conductance
      systems and determines the excitability of these neurons.

PMID- 1361670
TI  - The effects of sandostatin and somatostatin on nociceptive transmission in the
      dorsal horn of the rat spinal cord.
AB  - The role of somatostatin and a stable analogue, sandostatin (Octreotide), on the
      responses of spinal cord neurones in vivo was investigated in the rat. Electrical
      C-fibre stimulation was used as a model of acute nociception and the response to
      subcutaneous formalin was used as a model of longer term events. Intrathecal pre
      treatment with sandostatin and somatostatin did not alter the C-fibre response,
      wind up or A beta responses of the cells. However, intrathecal pre-treatment with
      sandostatin and somatostatin inhibited both the first and second phases of the
      formalin response dose dependently. Thus, sandostatin (20 micrograms) and
      somatostatin (150 micrograms) inhibited the first phase (66 +/- 12% inhibition
      and 52 +/- 13% respectively) and second phase (91 +/- 2% inhibition and 39 +/-
      16% inhibition respectively). The second phase of the formalin response was more
      sensitive to somatostatin and sandostatin than the first. Sandostatin was
      approximately 400 times more potent than somatostatin on the second phase of the
      response. Subcutaneous sandostatin (100 mg/kg) significantly inhibited both the
      first and second phase of the formalin response whereas the local peripheral
      administration of sandostatin (20 micrograms) only inhibited the second phase of
      the formalin response.

PMID- 1361672
TI  - International Symposium on Adhesives in Dentistry. Omaha, Nebraska, 11-13 July
      1991.

PMID- 1361671
TI  - Cold weather injuries during peacetime military training.
AB  - Demographic data on 220 cold weather injuries seen over a 52-month period at the
      67th Evacuation Hospital in Wuerzburg, Germany, was reviewed. Data were collected
      at the time of presentation and all diagnoses were made by a general/vascular
      surgeon. Statistics on age, gender, race, rank, unit, prior injury, use of
      tobacco products, classes on prevention, and activity at the time of injury were
      reviewed. Previously identified risk factors were confirmed except for tobacco
      use. There appeared to be no risk associated with gender or rank. Most injuries
      were sustained by soldiers performing low-risk activities for which no clear
      predisposing event could be ascribed. Prevention and early detection appear
      critical since injuries were not necessarily associated with specific actions or
      events.

PMID- 1361673
TI  - Effect of induced molting on B cell and CT4 and CT8 T cell numbers in spleens and
      peripheral blood of White Leghorn hens.
AB  - Two trials were conducted to examine the possible effect of induced molting on
      splenic and peripheral blood T and B cells. Molting was achieved using shortened
      light exposure and a 14-day fast. Feed was removed on Day 0 and blood for
      analysis was removed on Days 3, 10, and 17 whereas spleens were removed on Days
      4, 11, and 18. Fluorochrome-labeled anti-chicken CT4 and CT8 monoclonal
      antibodies were used to examine molting effects on chicken T cells and polyclonal
      anti-chicken immunoglobulin was used to detect chicken B cells. The labeled cell
      preparations were analyzed by flow cytometry. Molted hens had significantly
      decreased CT4+ peripheral blood T cells on Day 3 in both trials and on Day 10 in
      one trial. No effects on peripheral blood CT8+ T cells were observed. Splenic
      CT4+ T cells were decreased on Day 11 in one trial whereas splenic CT8+ T cells
      were significantly increased on Day 4 in two trials and on Day 11 in one trial.
      Peripheral blood and splenic B cells were largely unaffected in both trials.
      These results indicate that fasting to induce a molt does alter T lymphocyte
      subpopulations and these effects primarily occur early in the fasting procedure.

PMID- 1361674
TI  - The turkey major histocompatibility complex: identification of class II genotypes
      by restriction fragment length polymorphism analysis of deoxyribonucleic acid.
AB  - Using a chicken Class II MHC clone in Northern blot analysis, tissue-specific
      expression of turkey Class II MHC genes was observed in the embryonic bursa of
      Fabricius as well as in the adult spleen. In contrast, there was no detectable
      expression in the embryonic liver, brain, or spleen. Southern blot analysis of
      BamHI-digested turkey DNA revealed two restriction fragment length polymorphism
      (RFLP) patterns that did not deviate significantly from single-gene Mendelian
      inheritance. Further analysis of PvuII-digested DNA from 325 turkeys showed four
      distinct RFLP patterns that segregated within the turkey lines studied. Because
      the chicken Class II MHC clone hybridized specifically to mRNA in immune
      associated tissues, and because it identified polymorphisms among turkeys, the
      chicken clone is suggested to identify four turkey Class II MHC genotypes. The
      current study provides good evidence that RFLP analysis of DNA can be used as a
      means for molecular genotyping at the MHC in turkeys.

PMID- 1361675
TI  - [Seroprevalence of hemorrhagic fever with renal syndrome in foresters of Ile-de
      France].

PMID- 1361676
TI  - Distribution and amounts of taxol in different shoot parts of Taxus cuspidata.
AB  - Different fresh shoot parts of male and female plants of Taxus cuspidata were
      extracted and analysed for taxol concentration by high performance liquid
      chromatography (HPLC). Extracted parts included: young needles (first 10 top
      needle pairs of 30 cm long branches), old needles (last 10 needle pairs of 30 cm
      long branches), green bark, dark bark (with intense secondary growth), young wood
      (originally surrounded by green bark), wood (originally surrounded by dark bark),
      young stems (surrounded by green bark and devoid of needles), and mature male
      cones. Dichloromethane extracts were analysed by HPLC and diode array
      spectroscopy. Taxol identification was done by retention time, U.V. spectra, and
      spiking with an authentic taxol standard; 1H-NMR analysis was done for needle
      extracts. All parts except male cones had measurable amounts of taxol; no effect
      of plant sex on taxol levels of the plant parts analysed was observed. Results
      indicated that the bark accounted for almost all the taxol present in stems
      devoid of needles. Needles showed the highest levels of taxol (overall average of
      0.035 +/- 0.006% of the extracted dry weight), significantly higher than those
      displayed by dark bark samples (0.012 +/- 0.001% of the extracted dry weight).
      Different needle post-harvesting procedures were evaluated in relation to taxol
      yields, 96 h dark incubation at -12 degrees C and 96 h dark incubation at 25
      degrees C under vacuum gave taxol yields equivalent to those of freshly extracted
      samples. However, results obtained for 96 h dark incubation at 60 degrees C
      indicated some extent of taxol degradation.

PMID- 1361677
TI  - Contractile effects of prostaglandin E2 in rat rectum: sensitivity to the
      prostaglandin antagonists diphloretin phosphate and SC 19220.
AB  - Prostaglandin E2 (PGE2) applied cumulatively (1 nM-1 microM) induced
      concentration-dependent tonic contractions in the longitudinal muscle of isolated
      rat rectum. The PGE2 effects were not altered by guanethidine (50 microM),
      whereas atropine (3 microM), guanethidine plus atropine or tetrodotoxin (0.1
      microM) reduced them to an almost equal extent and increased the EC50 values for
      PGE2. The after-contractions following electrical stimulation were enhanced by
      PGE2 (10 nM) and inhibited by atropine. Diphloretin phosphate (DPP, 100 microM)
      shifted the regression lines for PGE2 to the right in both untreated and
      tetrodotoxin-treated preparations, and thereby increased the EC50 values. Slopes
      of the concentration-effect lines for PGE2 before and after DPP differed in the
      presence of tetrodotoxin. The regression line for PGE2 with SC 19220 (100 microM)
      in tetrodotoxin-treated preparations was shifted to the right in a parallel
      fashion. It is concluded that PGE2 exerted both a neural (cholinergic) and a
      smooth muscle effect. There may be a competitive antagonism between SC 19220 and
      PGE2 but the block by DPP may be nonselective.

PMID- 1361678
TI  - Effects of EP-receptor subtype specific agonists and other prostanoids on
      adenylate cyclase activity of duodenal epithelial cells.
AB  - Rank order of agonist potency for activation of adenylate cyclase by the
      naturally occurring prostanoids PGE2, PGF2 alpha, PGD2, the stable PGI2 analogue
      iloprost, and the TXA2 mimetic U 46619, provides evidence for the existence of a
      distinct PGE-receptor on guinea-pig duodenal enterocytes. The PGE-receptor is
      likely to be of the EP2-subtype since the specific EP2-agonist 11-deoxy-PGE1
      stimulated adenylate cyclase activity with a 20-fold higher potency than the EP1
      agonist 17-phenyltrinor-PGE2 and the EP3-agonists MB 28767 and GR 63799. In
      addition, sulprostone (acting on both EP1- and EP3-receptors) was ineffective.
      Since the specific EP1-antagonist SC 19220 did not inhibit PGE2-stimulated
      adenylate cyclase activity, the involvement of EP1-receptors could be further
      excluded. The synthetic prostaglandin E-analogues misoprostol and nocloprost
      stimulated adenylate cyclase almost identically, though they were about 10-fold
      less potent than the natural PGE2.

PMID- 1361679
TI  - Controversies in respiratory medicine: regular inhaled beta-agonists--clear
      clinical benefit or a hazard to health? (1). Beta-agonists can be used safely and
      beneficially in asthma.

PMID- 1361680
TI  - Controversies in respiratory medicine: regular inhaled beta-agonists--clear
      clinical benefit or a hazard to health? (2). Why beta-agonists should not be used
      regularly.

PMID- 1361682
TI  - Obstructive Sleep Apnea. Proceedings of a symposium. Grenoble, France, December
      11-12, 1991.

PMID- 1361681
TI  - [Cytosolic oncogenic neu protein determined with enzyme immunoassay:
      approximation to a marker of clinical application].

PMID- 1361683
TI  - [The effect of acute poisoning of rats with carbaryl on the transamination
      reactions involving alpha-ketoglutarate. Part I. Activity of plasma
      aminotransferases].
AB  - White male Wistar rats were poisoned orally with a single carbaryl dose 474 mg/kg
      (1/2 LD50). In the plasma of control animals and 2, 4, 24 and 72 hours after
      administration of the insecticide the activity of aminotransferase catalysing the
      reactions between alpha-ketoglutarate and six amino acids (cysteine, lysine,
      phenylalanine, leucine, asparagine and valine) was determined. Aminotransferases
      activity was expressed as the amount of glutamic acid developing during
      incubation of 1 cm3 of plasma for 1 hour. Glutamic acid was determined
      spectrophotometrically after chromatographic separation on paper. The results of
      the investigations demonstrated that acute intoxication with carbaryl caused a
      statistically significant increase in the activity of two aminotransferases in
      the plasma of experimental animals. A rise in the activity of the enzyme
      catalysing the reaction between alpha-ketoglutarate and asparagine ketoglutarate
      and lysine was observed.

PMID- 1361684
TI  - NO news is good news.
AB  - A startlingly simple molecule unites neuroscience, physiology, and immunology,
      and revises scientists' understanding of how cells communicate and defend
      themselves.

PMID- 1361685
TI  - Impaired long-term potentiation, spatial learning, and hippocampal development in
      fyn mutant mice.
AB  - Mice with mutations in four nonreceptor tyrosine kinase genes, fyn, src, yes, and
      abl, were used to study the role of these kinases in long-term potentiation (LTP)
      and in the relation of LTP to spatial learning and memory. All four kinases were
      expressed in the hippocampus. Mutations in src, yes, and abl did not interfere
      with either the induction or the maintenance of LTP. However, in fyn mutants, LTP
      was blunted even though synaptic transmission and two short-term forms of
      synaptic plasticity, paired-pulse facilitation and post-tetanic potentiation,
      were normal. In parallel with the blunting of LTP, fyn mutants showed impaired
      spatial learning, consistent with a functional link between LTP and learning.
      Although fyn is expressed at mature synapses, its lack of expression during
      development resulted in an increased number of granule cells in the dentate gyrus
      and of pyramidal cells in the CA3 region. Thus, a common tyrosine kinase pathway
      may regulate the growth of neurons in the developing hippocampus and the strength
      of synaptic plasticity in the mature hippocampus.

PMID- 1361687
TI  - HLA-DP polymorphism in northern Italian celiac patients.
AB  - The contribution of HLA-DP genes to celiac disease susceptibility has been
      investigated in 95 Italian patients, 41 with childhood and 54 with adult disease
      onset. Polymerase chain reaction amplification, sequence-specific oligonucleotide
      probe hybridization and restriction fragment length polymorphism analyses have
      been carried out. All celiac patients and 56 out of 128 random healthy controls
      were DQw2-positive. The frequency of the DPB1*0101 allele was significantly
      increased (pc = 0.002, relative risk 5.21) in patients with celiac disease
      (23.2%) compared to the whole panel of controls (5.5%), but not to the 56
      controls bearing DQw2 (10.7%). No significant difference in the frequency of
      DPB1*0101 was found between celiac patients with pediatric (24.4%) or adult
      (22.2%) onset. The DPB1*0101 allele was associated with both the DR3-DQw2 and DR7
      DQw2 haplotypes. Moreover, our study has not confirmed the association with
      DPB1*0402 and DPB1*0301 previously reported in celiac children from southern
      Italy. The linkage of the DPB1*0101 allele with the DQ locus and the observation
      that the DP but not the DQ association appears to be ethnically dependent
      strongly support a secondary role of DP molecules in celiac disease
      susceptibility.

PMID- 1361686
TI  - HLA-DPB typing using co-digestion of amplified fragments allows efficient
      identification of heterozygous genotypes.
AB  - Twenty-four alleles have been defined for HLA-DPB based on their second exon
      sequences. This paper describes a novel method, co-digested amplified fragment
      length polymorphisms (CAFLP), for assigning these alleles to heterozygous
      patients, as well as to homozygous cell lines. The method depends on co-digestion
      of amplified DNA by restriction endonucleases and separation of the resultant
      fragments with polyacrylamide gel electrophoresis. Co-digestion by selected
      restriction enzymes produces a set of readily discernible fragments that are
      unique for a given haplotype because the selected restriction sites occur in cis.
      Consequently, this method provides haplotype information not available from
      independent digests and allows all known heterozygous genotypes to be identified.
      Analysis of 103 trios of mother, father, and child, plus 120 normal caucasians,
      demonstrates the reliability and simplicity of this procedure. This simple typing
      method results in unambiguous assignment of all current HLA-DPB genotypes in
      random samples with a high proportion of heterozygous individuals.

PMID- 1361688
TI  - Distribution of HLA antigens in Spanish Gypsies: a comparative study.
AB  - We have studied the HLA-class I and class II antigen distribution in a sample of
      75 Spanish Gypsies and 74 Spanish non-Gypsies by serology, restriction fragment
      length polymorphism, and protein chain reaction and hybridization with allele
      specific oligonucleotide probes. When both population samples are compared, we
      find that Gypsies have a statistically significantly higher frequency of A1, A11,
      B61, Cw6, DQ5 and haplotypes DR16 DQ5 Dw21 and DR14 DQ5 Dw9 DR52b. Frequency of
      A3, A29, B44, DR4, DQ2, DQ8 and haplotypes DR1 DQ5 and DR7 DQ2 DB17 DR53 are
      significantly lower in this ethnic group. The analysis of the serological data in
      the two populations demonstrates that Cw6 can be split into long Cw6 (Cw6.1) and
      short Cw6 (Cw6.2). Haplotype A1-Cw6-B61-DR14-DQ5 is the most characteristic in
      Gypsies, with a frequency of 13%. Estimation of the genetic distances shows that
      Spanish Gypsies are closer to Indian Caucasoid populations than to the Spanish
      non-Gypsy population. HLA data support the proposed historical origin of this
      ethnic group.

PMID- 1361690
TI  - A qualitative assessment of developmental toxicity within a series of
      structurally related dopamine mimetics.
AB  - A qualitative assessment of developmental toxicity within a series of 12
      structurally related compounds, 11 of which were active dopamine mimetics and one
      was inactive, was conducted in rats treated orally by gavage during the major
      period of organogenesis. Doses were chosen where possible to be equipotent in
      terms of pharmacological activity. The series was typified by the compound BRL
      16644 (2-[[3,4-dihydro-2,2-dimethyl-4-[3-(trifluoromethyl)phenyl]- 2H-1
      benzopyran-7-yl]oxy]-N,N-dimethyl-ethanamine: Chemical Abstracts No. 59257-24-8).
      Five of these compounds were clearly teratogenic producing specific abnormalities
      typified by anasarca, brachygnathia and cleft palate. Similar levels of maternal
      toxicity, particularly stereotypic behaviour, and foetotoxicity were seen in both
      teratogenic and non-teratogenic compounds suggesting that neither maternal nor
      foetotoxicity plays a role in the aetiology of the abnormalities. Four of the
      teratogenic compounds contained a trifluoromethyl group in the 4-phenyl ring and,
      within this series of compounds, substitution with this group appears to confer
      teratogenicity. Although equipotent doses were used this only pertained to the
      adult and as only limited pharmacokinetic data were available, including the
      extent of placental transfer, the influence of this group is not clear.
      Investigations have been undertaken to relate the teratogenic potential of these
      compounds to a number of their chemical descriptors, including electronic,
      steric, quantum chemical and hydrophobicity parameters, to try and clarify the
      influence of the trifluoromethyl group.

PMID- 1361689
TI  - The effects of 2,3,5-(triglutathion-S-yl)hydroquinone on renal mitochondrial
      respiratory function in vivo and in vitro: possible role in cytotoxicity.
AB  - Administration of 2,3,5-(triglutathion-S-yl)hydroquinone [2,3,5-(triGSyl)HQ] to
      rats causes severe renal proximal tubular necrosis. Although the cellular
      target(s) for 2,3,5-(triGSyl)HQ is not known, substantial evidence implicates
      mitochondria as the primary cellular target for aliphatic S-conjugates. To
      determine whether mitochondria are targets for 2,3,5-(triGSyl)HQ, the in vivo and
      in vitro effects of this conjugate on rat renal mitochondria (RRM) were
      investigated. In vitro exposure of RRM to 2,3,5-(triGSyl)HQ inhibited site I
      supported respiration to a much greater extent than site II-supported
      respiration. Inhibition of mitochondrial function, as manifested by decreases in
      the respiratory control ratios, were a consequence of significant elevations in
      state 4 respiration. Inhibition of constitutive gamma-GT activity with AT-125 had
      no effect on the ability of 2,3,5-(triGSyl)HQ to decrease mitochondrial function.
      The effects of 2,3,5-(triGSyl)HQ on mitochondrial function in vivo were
      subsequently assessed. Shortly (0.5-2.0 hr) following administration of 2,3,5
      (triGSyl)HQ (20 mumol/kg, iv) to rats, a significant elevation of state 4
      respiration was observed. Thereafter (4-16 hr) state 4 respiration returned to
      control values and state 3 respiration became significantly depressed. A total
      collapse in RRM function occurred by 24 hr. The effects of 2,3,5-(triGSyl)HQ on
      state 4 respiration preceded significant elevations in blood urea nitrogen, which
      occurred at 8 hr. However, pretreatment of animals with probenecid, an inhibitor
      of organic anion transport, caused a significant decrease in the 2,3,5
      (triGSyl)HQ-mediated elevations in state 4 respiration at 1 hr, without
      preventing the subsequent development of renal necrosis. In contrast, AT-125,
      which protected animals from 2,3,5-(triGSyl)HQ-mediated nephrotoxicity, had no
      effect on the early (1 hr) elevations in state 4 respiration but did prevent the
      later (8 hr) decreases in state 3 respiration. The data suggest that the early
      elevation in state 4 respiration observed in vivo is unlikely to contribute to
      2,3,5-(triGSyl)HQ-mediated nephrotoxicity. The relationship between the decrease
      in state 3 respiration seen at later time points and the subsequent development
      of toxicity require further study before a cause and effect relationship can be
      determined.

PMID- 1361691
TI  - Multivariate quantitative structure-toxicity relationships in a series of
      dopamine mimetics.
AB  - The techniques of principal components analysis and non-linear mapping are
      routinely used by computer chemists at SmithKline Beecham Pharmaceuticals in the
      process of drug development by relating the structure of a compound to its
      chemical activity. To our knowledge these techniques had not previously been
      applied to the association between the structure of a compound and its
      toxicological properties. Using a series of 12 structurally related compounds (11
      were active dopamine mimetics and one was inactive), of which five were known to
      be teratogenic and seven were non-teratogenic, it was possible to demonstrate
      that molecular modelling techniques could be applied to differentiate
      toxicological data. The structure/property relationships of these compounds were
      investigated using calculated physicochemical properties, molecular modelling and
      multivariate statistical techniques. A data set of 56 molecular descriptors was
      used to represent this series of compounds. Analysis of the data set using
      principal components analysis and non-linear mapping suggested that
      teratogenicity was associated with four molecular properties. Moreover, the
      electronic nature of the 4-phenyl group appeared to be an important determinant
      of the teratogenesis.

PMID- 1361693
TI  - Toxicology from discovery and experimentation to the human perspective.
      Proceedings of the VIth International Congress of Toxicology. Rome, Italy, 28
      June - 3 July 1992.

PMID- 1361692
TI  - In vitro evidence for the role of glutamate in the CNS toxicity of mercury.
AB  - Intoxication with elemental mercury vapor or with methylmercury results in the
      accumulation of mercuric mercury (Hg2+) in the brain. Submicromolar
      concentrations of Hg2+ were shown previously to inhibit glutamate uptake in
      astrocyte cultures selectively and reversibly. This finding suggests that
      blockade of the inactivation of synaptically released glutamate is a potential
      mechanism of the CNS toxicity of Hg2+. The present study shows further that Hg2+
      (< or = 1 microM): (i) markedly inhibits the clearance of extracellular glutamate
      both by astrocyte cultures and by spinal cord cultures; (ii) reduces glutamine
      content and export in astrocyte cultures; (iii) has little effect on neuronal
      viability in spinal cord cultures in the absence of excitotoxic accumulations of
      glutamate; (iv) does not impair the sensitivity of neurons to the excitotoxic
      action of glutamate. Also, it is noted that Hg2+ (< or = 1 microM) has not been
      shown to impair transmitter release acutely in existing studies of presynaptic
      actions. Thus, the available evidence from in vitro studies is consistent with
      the hypothesis that low concentrations of mercuric mercury in the brain can cause
      neurotoxicity by selectively inhibiting the uptake of synaptically released
      glutamate, with consequent elevation of glutamate levels in the extracellular
      space.

PMID- 1361694
TI  - Glutamate transmission is involved in the mechanisms of neuronal degeneration
      produced by intrahippocampal tetanus toxin in rats.
AB  - Tetanus toxin (TT) blocks GABA-mediated inhibitory neurotransmission in the
      mammalian CNS via selective inhibition of transmitter release. The loss of
      central inhibition produces an excitatory focus resembling human limbic epilepsy.
      We now report that the net excitation caused by an unopposed action of glutamic
      acid may also produce neuronal degeneration in the rat brain. Anaesthetized rats
      were placed in a stereotaxic frame and TT (1 microliter dissolved in phosphate
      buffer, pH 7.0) was injected unilaterally into the dorsal hippocampus. Injection
      of TT (1000 mouse minimum lethal doses, MLDs; n = 3-6 rats per group) produced
      time-dependent neuronal loss in the CA1 pyramidal cell layer which was
      significant (p < 0.05) 7 and 10 days, but not 1 day, after the injection.
      Systemic treatment with competitive (CGP 37849, 3 mg/kg i.p) or non-competitive
      (MK801, 0.3 mg/kg i.p.) antagonists at the N-methyl D-aspartate (NMDA) receptor
      complex 1 h before and 1 h after TT and then once daily for 10 days protected
      rats from the hippocampal damage produced by TT (1000 MLDs). In addition, in rats
      bearing a monolateral surgical lesion of the Schaffer collaterals, through which
      CA1 neurones receive a robust excitatory input from CA3 pyramids, the bilateral
      injection of TT (1000 MLDs/side) produced significant neuronal loss in the
      unlesioned hippocampus whereas the contralateral appeared to be preserved. In
      conclusion, these results demonstrate that excitatory neurotransmission may be
      involved in the neuropathology elicited by intrahippocampal TT in rats.

PMID- 1361695
TI  - Idiopathic CD4+ T-lymphocytopenia (ICL) and the safety of blood transfusions:
      what do we know and what should we do?

PMID- 1361696
TI  - Blood donor deferral registries: highlights of a conference.

PMID- 1361697
TI  - Computed tomography of the brain, hepatotoxic drugs and high alcohol consumption
      in male alcoholic patients and a random sample from the general male population.
AB  - Computed tomography (CT) of the brain was performed in a random sample of a total
      of 195 men and 211 male alcoholic patients admitted for the first time during a
      period of two years from the same geographically limited area of Greater
      Stockholm as the sample. The same medical, social and neuroradiological methods
      were used for examination of the alcoholic inpatients as for the random controls.
      Laboratory tests were performed, including liver and pancreatic tests.
      Toxicological screening was performed and the consumption of hepatotoxic drugs
      was also investigated and the following were the types of drugs used:
      antiarrhythmics, antiepileptics, antiphlogistics, mixed analgesics, barbiturates,
      sulphonamides, benzodiazepines, clomethiazole and phenothiazine derivatives, all
      of which are metabolised by the liver. The group of male alcoholic inpatients and
      the random sample were then subdivided with respect to alcohol consumption and
      use of hepatotoxic drugs: Group IA, men from the random sample with low or
      moderate alcohol consumption and no use of hepatotoxic drugs; IB, men from the
      random sample with low or moderate alcohol consumption with use of hepatotoxic
      drugs; IIA, alcoholic inpatients with use of alcohol and no drugs; and IIB,
      alcoholic inpatients with use of alcohol and drugs. Group IIB was found to have a
      higher incidence of cortical and subcortical changes than group IA. Group IB had
      a higher incidence of subcortical changes than group IA, and they differed only
      in drug use. Groups IIB and IIA only differed in drug use, and IIB had a higher
      incidence of brain damage except for anterior horn index and wide cerebellar
      sulci indicating vermian atrophy. Significantly higher serum (S) levels of
      bilirubin, gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase
      (ASAT), alanine amino-transferase (ALAT), creatine kinase (CK), lactate
      dehydrogenase (LD) and amylase were found in IIB. The results indicate that drug
      use influences the incidence of cortical and subcortical aberrations, except
      anterior horn index. It is concluded that the groups with alcohol abuse who used
      hepatotoxic drugs showed a picture of cortical changes (wide transport sulci and
      clear-cut or high-grade cortical changes) and also of subcortical aberrations,
      expressed as an increased widening of the third ventricle.

PMID- 1361698
TI  - [The problems of enhancing the quality and the development of new drug forms of
      vaccinal preparations].

PMID- 1361699
TI  - [The concept of the integrative function of the cerebrospinal fluid in the
      activities of the central nervous system].

PMID- 1361700
TI  - Proceedings of the 1st European Conference on Vaccinology. Annecy, France, 16-17
      March 1992.

PMID- 1361702
TI  - [The "Emmerich Arthritis Record", function and acceptance within the scope of an
      integrated treatment concept].
AB  - For a comprehensive model of rheumatoid arthritis treatment, we designed an
      arthritis manual for continuous treatment of chronic illness. One goal of
      introducing the manual to the patients was the improvement of communication
      between patient and different doctors and therapists. The first part includes of
      a doctor's documentation sheet and a patient calendar (6 months each) for daily
      self-documentation of drug compliance. The second part is a daily pain-rating
      scale. The 3-year evaluation of 655 patient manuals for 286 patients was analyzed
      to estimate the compliance in using the manual. Overall, 87% of diagnoses, 83% of
      disease-modifying anti-rheumatic drugs (DMARDs), 87% of non-steroidal anti
      rheumatic drugs (NSAIDs) had been documented in the manual. Data indicates that
      the general practitioner and the rheumatologist accepted the manual form. In
      addition, 85% of the documented patients used the DMARDs, 74% used the daily pain
      score, and 43% the daily physiotherapy. Subgroup data (n = 130 RA patients)
      suggest additional results: 1) there was no difference in sociodemographic data
      between the patient manual user group and the non-user group; 2) the user group
      consisted of patients with higher disease activity (ARA-criteria), higher pain
      score, and negative mood pattern. Furthermore, the user group was more active in
      daily physiotherapy, ergotherapy, and balneotherapy.

PMID- 1361701
TI  - Molecular design of cholera vaccines.
AB  - Cholera is still a serious public health problem in developing countries,
      particularly those in tropical regions. This has stimulated considerable research
      into the molecular analysis of pathogenesis resulting in the identification of a
      number of critical components required for both colonization of the gut mucosa
      and the disease symptoms. These components are the targets for rational molecular
      approaches to vaccine development.

PMID- 1361703
TI  - [The importance of S-100 protein positive Langerhans cells and Leu-M1 positive
      tumor cells for prognosis of papillary thyroid cancer].
AB  - In a period of 10 years (1981-90) papillary thyroid carcinomas were found in 124
      cases. In 95 cases we were able to perform immunohistochemical studies for Leu-M1
      antigen and S-100 protein. The examination of these cases has revealed that the
      presence of S-100 positive Langerhans cells yields no additional information for
      the prognosis of the papillary thyroid carcinoma. But we observed that the
      existence of Leu-M1 positive tumour cells is connected with a poor postoperative
      course of disease in comparison to Leu-M1 negative tumours.

PMID- 1361704
TI  - Spermatic and peripheral venous plasma concentrations of immunoreactive inhibin
      in prepubertal boys with undescended testis and in pubertal boys with varicocele.
AB  - To obtain more information about testicular inhibin secretion in the prepubertal
      and pubertal human male, we measured the concentrations of immunoreactive inhibin
      with a heterologous radioimmunoassay in the spermatic and peripheral venous
      plasma of 5 prepubertal boys with unilateral undescended testis (Group I, P1), 3
      prepubertal boys with inguinal hernia (Group II, P1), and 12 pubertal boys with
      left idiopathic varicocele. The latter subjects were divided, according to the
      degree of their pubertal development, in early pubertal (Group III, N = 5, P2)
      and mid-pubertal groups (Group IV, N = 7, P3-4). In Group I, the mean (+/- SD)
      spermatic venous concentrations of inhibin (289.4 +/- 120.4 ml eq/l) were
      significantly higher than the corresponding mean peripheral venous concentrations
      (162.6 +/- 47.2; p < 0.02) suggesting active testicular secretion of inhibin. In
      Group II, the spermatic-peripheral inhibin gradient was not significant. In
      pubertal boys with idiopathic varicocele, the mean concentrations of spermatic
      inhibin were 1076.6 +/- 532.0 and 1023.4 +/- 274.5 in Groups III and IV,
      respectively. These levels were about five times higher than the corresponding
      peripheral concentrations (204.8 +/- 41.9 and 238.9 +/- 38.9; p < 0.005 and p <
      0.001, respectively). When the data of all the boys were considered together the
      spermatic venous concentrations of inhibin were significantly correlated with
      those of peripheral venous FSH (r = 0.4749, p < 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1361705
TI  - Increased hypothalamic somatostatin mRNA following dexamethasone administration
      in rats.
AB  - There is increasing evidence to suggest that supraphysiological doses of
      glucocorticoids suppress growth hormone secretion in vivo by augmenting
      somatostatin release from the hypothalamus; previously, we reported an increase
      in hypothalamic somatostatin content in dexamethasone-treated rats. To further
      examine whether the production of somatostatin really is augmented, hypothalamic
      somatostatin mRNA levels were determined by the Northern blot technique in female
      rats receiving 330 micrograms of dexamethasone daily for three days. In two
      series of experiments, hypothalamic somatostatin mRNA levels in dexamethasone
      treated rats were significantly (p < 0.05) increased to 133 +/- 19 (mean +/- SD)%
      and 153 +/- 38% of the controls. In the dexamethasone-treated rats, plasma growth
      hormone levels were markedly suppressed compared with those of the controls.
      These results further support the hypothesis that pharmacological doses of
      glucocorticoids increase the production and release of somatostatin from the
      hypothalamus and thus inhibit growth hormone secretion, overriding the direct
      stimulatory effect of glucocorticoids on growth hormone production at the
      pituitary level.

PMID- 1361706
TI  - Antabuse. Proceedings of the Elsinore Antabuse Conference. Elsinore, Denmark, 7-8
      November 1991.

PMID- 1361707
TI  - [Extra-articular fractures near the knee and concomitant knee damage].
AB  - While the prognosis of intra-articular fractures of the knee joint is determined
      by the reconstruction of the articular surfaces, ligamentous damage and resulting
      joint instability is a main problem with extra-articular fractures neighbouring
      the knee. In a follow-up of 43 cases of A 1-3 fractures according to the AO/ASIF
      classification, 37.2% of the patients revealed concomitant ligamentous damage.
      Especially supracondylar femoral fractures and the avulsion fractures of the
      posterior cruciate and lateral collateral ligament are at higher risk.-
      Ligamentous ruptures accompanying avulsion fractures should be treated primarily
      according to the rules of knee joint surgery. In cases of supracondylar femoral
      fractures after open reduction and internal fixation the recovery of knee joint
      motion is more important than joint stability. Therefore ligamentous repair has
      to be performed secondarily if necessary.

PMID- 1361708
TI  - [Double plate compound osteosynthesis. A procedure for primary stress-stable
      management of problem injuries of the subtrochanteric to supracondylar femoral
      area].
AB  - Full loading capacity cannot be achieved with standard implants in reversed
      trochanteric, subtrochanteric and supracondylar femur fractures. A full loading
      capacity is essential for elderly patients because a load free mobilisation is
      not possible and in pathological and impending pathological fractures because of
      the short life expectancy of these patients. On the basis of a proposal by Ganz
      we developed a double plate compound osteosynthesis (DPCO) with very high loading
      capacity for all these types of fractures. The technique is presented.

PMID- 1361709
TI  - [Application of the Isler and Ganz classification of pelvic ring fractures in
      clinical practice].
AB  - The classification of pelvic fractures proposed by Isler and Ganz was applied to
      152 patients. On the basis of this experience, the following conclusion were
      drawn. 1. It is possible to classify all pelvic ring injuries by dividing them in
      lesions of the anterior and of the posterior ring segment. 2. The classification
      requires a thorough examination; often a CT scan is needed. The original
      classification of 9 out of 18 patients based on X-ray morphology had to be
      revised after CT examination. 3. Once the pelvic injury is definitely classified
      the mode of therapy is determined as well.

PMID- 1361710
TI  - [Results of surgical treatment of proximal biceps tendon rupture].
AB  - During a 9-year period we operated on 19 patients in whom the proximal tendon of
      the biceps brachii muscle had been disruptured. Various surgical techniques were
      employed, such as refixation at the processus coracoideus, tenodesis in the
      sulcus intertubercularis, keyhole operation, in combination with an
      intraarticular inspection, revision, or if necessary widening of a narrow passage
      ("defile"). Follow-up was possible in 15 patients for an average period of 3
      years after the operation, in respect of clinical, roentgenological and
      isokinetic findings. Results were mainly good while employing a variety of
      different surgical techniques; in only 3 patients the shoulder function remained
      restricted, painful and/or weakened. The isokinetic maximum torque was either
      increased on the operated side (after coracoid refixation) or reduced (after
      tenodesis in the sulcus). The underlying biomechanical causes are explained. Good
      results can be obtained in surgical treatment of the rupture of the proximal
      biceps tendon provided the procedure is accurately executed while taking into
      consideration, at the same operation stage, the associated pathology of the
      rotatory cuff. For biomechanical reasons, preference should be given to the
      operations according to Hitchcock and Bechtol in respect of refixation, and to
      the keyhole operation method.

PMID- 1361711
TI  - [Roentgen diagnosis of post-traumatic radius torsion].
AB  - Especially the identification of rotational malunions on the distal radius is
      difficult by routine diagnosis. Long-time effects like a chronic loss of
      articular surface of the posttraumatic rotation on the distal radioulnar joint
      are of clinical importance. Evading expensive diagnostic methods like CT
      simulated rotational malunions of the radius are quantitatively investigated on
      the basis of routine X-ray pictures only. The geometrical relation between the
      rotational angle of the radius and the two-dimensional distance from the dorsal
      to the volar border of the radial notch is described by a simple trigonometrical
      function. Considering morphological individualities of the radial notch and the
      rotational angles of right and left radii rotational malunions below 10 degrees
      are discovered and their effects on the forearm skeleton are assessed.

PMID- 1361712
TI  - [Clinical experience with collagenous wound dressing in severe traumatic soft
      tissue injuries].
AB  - We treated 34 patients during 1987-1990 with a collagen wound dressing. Eleven
      patients had traumatic soft tissue defects, 10 patients had 3 degrees-grade open
      fractures, 7 patients had infected soft tissue wounds and 6 patients had deep 2
      degrees and 3 degrees-degree burns. Our clinical experience confirmed the
      excellent clinical experimental results of collagen wound dressings. In all cases
      after 4 until 6 days of treatment good granulation and vascularisation of the
      wound bed was obtained, so that a skin transplant could be performed, which in
      all cases healed primarily. Moreover, the wound dressing had a good antibacterial
      effect and integrated actively in the wound healing process.

PMID- 1361713
TI  - [Healing of a deep skin wound using a collagen sponge as dressing in the animal
      experiment].
AB  - The high number of available wound dressing materials as well as the scientific
      reports about the topic indicates that the problem of an ideal wound dressing is
      not jet solved. In the last thirty years lot of scientific reports about collagen
      as wound covering has been published. The positive effect of collagen by his
      application on a wound ist well known. We investigated the effect of a collagen
      sponge on healing of full thickness skin wound in guinea pig. The animals were
      divided in two control groups and two experimental groups. In the control group
      there were air exposed wounds and another wounds covered with paraffin gauze. In
      the experimental groups were such wounds covered with natural reconstituted
      collagen sponge as well as wounds covered with chemically prepared collagen
      sponge with hexamethyldiisocyanat. The results were compared. The air exposed
      wounds healed in 50 days, the wounds covered with paraffin gauze healed in 48
      days. By covering the wounds with collagen sponge the healing was shortened in 24
      or 27 days respectively. Not only the healing time was shortened but also the
      quality of the wound repair by dressing the wounds with collagen sponge was
      enhanced.

PMID- 1361714
TI  - [Ligament repair with PDS (polydioxanone) in chronic insufficiency of the fibular
      ligament of the upper ankle joint: experimental and clinical experiences].
AB  - From September 1988 till February 1989, 14 patients with chronic ligamentous
      rupture of the ankle had been operated on using PDS-plasty. Of 12 patients
      checked in follow-up examination (mean postoperative period 45 weeks), only two
      showed good or very good results. Most patients had the same signs of chronic
      instability as preoperatively. Two patients had been reoperated on.
      Intraoperatively we did not find a biological substitute along the PDS guide
      line. In an experiment on the rat we examined histological changes and tensile
      strength at appointed times. Histological data showed no biological substitute of
      PDS. We also found residues of PDS even after 300 days. After a short time loss
      of tensile strength occurred. In view of an aseptical necrosis that occurred in
      our experiments, we must point out the risk of foreign body granulomas.

PMID- 1361715
TI  - ["Special occupational disability": a predominantly legal aspect in loss of
      earning capacity!].

PMID- 1361716
TI  - [Anatomic reconstruction of a rare combination injury of the axis (trans-dental
      dislocation with hanged-man fracture) by lag screw fixation].
AB  - The patient described here suffered from a Hanged-Man-Fracture type Effendi II in
      combination with a densfracture type Anderson d'Alonzo II. Options of treatment
      are discussed, the chosen therapy with lag-screw fixation described. The
      functional result was perfect.

PMID- 1361717
TI  - A symposium: Cardioprotection: Building a Consensus for the 1990s. Yorba Linda,
      California, November 10, 1991.

PMID- 1361718
TI  - Beta-adrenergic blockers as cardioprotective agents.
AB  - The evidence supporting and describing cardioprotective effects of beta
      adrenergic blocker treatment is surveyed. Details of the many studies that
      individually and collectively document the ability of long-term and acute beta
      blocker therapy to reduce overall mortality, sudden cardiovascular death, and
      nonfatal reinfarction in patients surviving or experiencing a myocardial
      infarction are described. A discussion of the mechanisms by which beta blockers
      probably and theoretically achieve these benefits includes the suggestion that
      they may reduce plaque rupture, thus indirectly inhibiting thrombosis. It is also
      suggested that, in the future, further cardioprotective benefits may accrue to
      the use of beta blockers in conjunction with thrombolysis and of beta blockers
      with a duration of action sustained throughout a full 24 hours.

PMID- 1361719
TI  - Divergent effects of taxol on tumor necrosis factor-alpha-mediated cytolysis of
      ovarian carcinoma cells.
AB  - OBJECTIVE: Our objective was to study the combined effect of taxol and tumor
      necrosis factor-alpha on the cytolysis of human ovarian carcinoma cell lines,
      because taxol has been shown to be active against ovarian carcinoma and has also
      been shown to increase tumor necrosis factor-alpha release from macrophages.
      STUDY DESIGN: The combined effect of taxol and tumor necrosis factor-alpha on the
      cell lines Caov-3, SK-OV-3, NIH:OVCAR-3, and A2780, which are sensitive to the
      cytolytic effect of tumor necrosis factor-alpha in the presence of inhibitors of
      protein synthesis, was investigated with a 24-hour chromium 51 release assay.
      RESULTS: At therapeutic concentrations taxol caused a significant increase in
      tumor necrosis factor-alpha-mediated cytolysis of Caov-3 and A2780 (p < or =
      0.05). By contrast, taxol caused a decrease in the tumor necrosis factor-alpha
      mediated cytolysis of SK-OV-3 and NIH:OVCAR-3 (p < or = 0.01). CONCLUSION: These
      results suggest that ovarian carcinomas have a heterogeneous response to the
      chemotherapeutic effect of taxol.

PMID- 1361721
TI  - A model of the transmission of dengue fever with an evaluation of the impact of
      ultra-low volume (ULV) insecticide applications on dengue epidemics.
AB  - We have developed a deterministic susceptible, exposed, infectious, resistant or
      removed (SEIR) model of dengue fever transmission that enables us to explore the
      behavior of an epidemic, and to experiment with vector control practices.
      Populations of both host and vector are divided into compartments representing
      disease status (susceptible, exposed, infectious, and, for humans, resistant),
      and the flow between compartments is described by differential equations.
      Examination of the equilibrium points leads to a formulation of the basic
      reproduction rate (Z0) of the disease. With a base set of parameters, Z0 = 1.9
      and the model realistically reproduces epidemic transmission in an
      immunologically naive population. Control of adult mosquitoes by ultra-low volume
      (ULV) aerosols is simulated by an abrupt decrease in vector densities, followed
      by gradual recovery of the vector population. The model indicates that ULV has
      little impact on disease incidence, even when multiple applications are made,
      although the peak of the epidemic may be delayed. Decreasing the carrying
      capacity of the environment for mosquitoes, and thus the basic reproduction rate
      of the disease, by source reduction or other means, is more effective in reducing
      transmission.

PMID- 1361720
TI  - The effect of interferon gamma on epidermal growth factor receptor expression in
      normal and malignant ovarian epithelial cells.
AB  - OBJECTIVE: We examined the effect of interferon gamma on proliferation and
      epidermal growth factor receptor expression in ovarian cancer cell lines and
      normal ovarian epithelial cells. STUDY DESIGN: The tritiated thymidine
      incorporation assay was used to assess the effect of interferon gamma on
      proliferation. Scatchard analysis of anti-epidermal growth factor receptor
      antibody binding, and Western blotting of immunoprecipitates was used to assess
      the effect of interferon gamma on epidermal growth factor receptor expression.
      RESULTS: Although interferon gamma elicited 30% to 40% decreases in
      proliferation, epidermal growth factor receptor expression was strikingly
      increased in all four ovarian cancer cell lines. Scatchard analysis indicated
      that this increase occurred primarily at the cell surface, but total cellular
      receptor levels also were increased. In contrast, interferon gamma treatment of
      normal ovarian epithelial cells affected neither proliferation nor epidermal
      growth factor receptor levels. CONCLUSION: Because the up-regulation of epidermal
      growth factor receptors by interferon gamma appears to be confined to malignant
      cells, interferon gamma may facilitate immunotherapy and imaging of ovarian
      cancers by means of immunoconjugates directed against the epidermal growth factor
      receptor.

PMID- 1361722
TI  - Arbovirus isolations from mosquitoes collected during 1988 in the Senegal River
      basin.
AB  - During August and September 1988, we collected adult mosquitoes from 14 locations
      in the Senegal River basin to search for evidence of Rift Valley fever (RVF)
      viral activity one year after the 1987 outbreak, which occurred along the Senegal
      Mauritania border. More than 62,000 specimens representing 18 species in seven
      genera were collected with carbon dioxide-baited, solid-state Army miniature
      light traps and sheep-baited traps. Twenty virus isolations from Culex, Aedes,
      and Anopheles mosquitoes were recovered from six locations: Fanaye Diery (11),
      Bode (four), Matam (two), Diongui (one), Ndialene (one), and Ngoui (one). Species
      yielding viral isolates were Anopheles pharoensis (eight), Culex
      tritaeniorhynchus (three), Cx. univitattus gr. (three), Cx. antennatus (two), Cx.
      poicillipes (two), Ae. hirsutus (one), and An. gambiae (one). Viruses were
      identified by complement fixation, and virus and plaque-reduction neutralization
      testing as Ngari (Bunyavirus, Bunyaviridae) (n = 15), Babanki (Alphavirus,
      Togaviridae) (n = 3), Bagaza (Flavivirus, Flaviviridae) (n = 1), and Bangui
      (Bunyavirus-like) (n = 1). No evidence of any RVF viral activity in the Senegal
      River Basin was detected in the mosquitoes tested.

PMID- 1361723
TI  - Decreased antihistamine metabolism.

PMID- 1361724
TI  - Bunazosin enhances receptor-mediated endocytosis of low-density lipoproteins.
AB  - The effects of bunazosin, an alpha 1-adrenergic receptor antagonist, on low
      density lipoprotein (LDL) receptor activity have been studied in cultured cells.
      Human skin fibroblasts, swine aortic smooth muscle cells and a human hepatoma
      cell line (Hep G2) were used for this study. Bunazosinm, at a concentration of 5
      x 10(-5) to 10(-4) M, increased 125I-LDL uptake with all of the cell lines and
      125I-LDL degradation with human skin fibroblasts and swine aortic smooth muscle
      cells. However, in human skin fibroblasts pretreated with lipoprotein deficient
      serum and Hep G2 cells, the degradation of 125I-LDL was decreased by bunazosin.
      These results suggest that bunazosin increases LDL receptor activity.

PMID- 1361725
TI  - Somatostatin inhibits vasopressin-stimulated phosphoinositide hydrolysis and
      influx of extracellular calcium in clonal hamster beta (HIT) cells.
AB  - Vasopressin (VP) stimulates insulin secretion and inositol phosphate (InsP)
      production in clonal hamster beta cells (HIT) via a cyclic AMP-independent V1
      receptor-mediated signal-transduction pathway. Somatostatin (SRIF) inhibited VP
      stimulated insulin secretion, and the effects of SRIF were abolished by
      pretreatment with pertussis toxin. The Ca(2+)-channel blockers verapamil and
      nifedipine also inhibited VP-stimulated insulin secretion during 20 min
      incubations, but verapamil was ineffective at 2 min, and the effects of SRIF and
      nifedipine together were not addictive. SRIF failed to inhibit further the
      attenuated insulin response to VP in Ca(2+)-free medium. VP-stimulated InsP
      production was also inhibited by SRIF in a pertussis-toxin-sensitive manner.
      Whereas VP-stimulated insulin secretion was almost completely inhibited by SRIF
      at an equimolar concentration, VP-stimulated InsP production was much less
      sensitive to inhibition by SRIF, even at a 100-fold excess concentration. VP
      increased cytosolic Ca2+ in HIT cells loaded with fura 2, the fluorescent Ca2+
      indicator. The increase was biphasic, with an initial rapid spike increase
      followed by a prolonged second phase. Both SRIF, at a concentration which
      inhibited VP-stimulated insulin secretion but not InsP production, and verapamil
      failed to inhibit the rapid spike increase in intracellular Ca2+, but did inhibit
      the second phase. We conclude that VP induces biphasic changes in cytosolic Ca2+,
      secondary to mobilization of intracellular Ca2+ and influx of extracellular Ca2+.
      SRIF inhibits insulin secretion by interrupting influx of extracellular Ca2+,
      likely by inhibiting Gi-subunit activity. Inhibition of VP-stimulated
      phosphoinositide hydrolysis, which is also pertussis-toxin-sensitive, may
      represent an additional mechanism of action of SRIF.

PMID- 1361727
TI  - Tetanus toxin action: inhibition of neurotransmitter release linked to
      synaptobrevin proteolysis.
AB  - Tetanus toxin is a potent neurotoxin that inhibits the release of
      neurotransmitters from presynaptic nerve endings. The mature toxin is composed of
      a heavy and a light chain that are linked via a disulfide bridge. After entry of
      tetanus toxin into the cytoplasm, the released light chain causes block of
      neurotransmitter release. Recent evidence suggests that the L-chain may act as a
      metalloendoprotease. Here we demonstrate that blockade of neurotransmission by
      tetanus toxin in isolated nerve terminals is associated with a selective
      proteolysis of synaptobrevin, an integral membrane protein of synaptic vesicles.
      No other proteins appear to be affected by tetanus toxin. In addition,
      recombinant light chain selectively cleaves synaptobrevin when incubated with
      purified synaptic vesicles. Our data suggest that cleavage of synaptobrevin is
      the molecular mechanism of tetanus toxin action.

PMID- 1361728
TI  - A comparison of single nucleotide primer extension with mispairing PCR-RFLP in
      detecting a point mutation.
AB  - A recent report by Petruzzella et al. (BBRC 186, 491-497, 1992) raised a question
      as to whether a point mutation in the mitochondrial ND2 gene (BBRC 182, 238-246,
      1992) is relevant to Alzheimer's disease. The argument was based on their
      inability to detect the point mutation at position 5460 in codon 331 in the DNAs
      extracted from 15 patients with Alzheimer's disease using mispairing PCR-RFLP. To
      clarify the discrepancy, we tested the DNAs reported by Petruzzella et al. for
      the mutation by single-nucleotide primer extension. The present work confirms our
      previous report and extends our finding of the point mutation in 8 of the 15 AD
      DNAs.

PMID- 1361726
TI  - Polarized distribution of neutral endopeptidase 24.11 at the cell surface of
      cultured human intestinal epithelial Caco-2 cells.
AB  - The human colon cancer cell line Caco-2 undergoes spontaneous enterocytic
      differentiation during growth, and expresses a number of brush-border-membrane
      associated hydrolases typical of a differentiated phenotype. Among these are
      alkaline phosphatase, dipeptidyl peptidase IV and sucrase-isomaltase (sucrase, EC
      3.2.1.48). Neutral endopeptidase 24.11 [EC 3.4.24.11, neprilysin (NEP)] is
      another abundant protease of normal enterocytes but its presence in Caco-2 cells
      has not been fully documented yet. In this paper, we show that Caco-2 cell
      extracts hydrolyse tritiated [D-Ala2Leu5]enkephalin with a Km of 180 microM, very
      close to the value obtained for the NEP present in the rabbit kidney (118
      microM). Western-blot analysis of brush-border membranes purified from post
      confluent cells revealed a protein with an apparent molecular mass of 94000 Da
      similar to that of the rabbit kidney NEP. The amount of enzyme in cell extracts
      increased as a function of the age of the culture, indicating that NEP expression
      is correlated with the degree of cell differentiation as is also the case for
      sucrase and dipeptidylpeptidase IV (DPP-IV). Binding of a radiolabelled antibody
      to Caco-2 cell monolayers grown on semi-permeable filters indicated that 95% of
      NEP molecules present at the cell surface are on the apical side.
      Immunocytochemical and flow cytometric analysis of intact and permeabilized cells
      were also used to investigate the presence of NEP and DPP-IV at the surface of
      Caco-2 cells. Whereas DPP-IV staining appeared to be homogeneous throughout the
      entire cell population, NEP-related fluorescence exhibited a bimodal distribution
      which indicates an uneven expression of the protein at the cell surface.
      Permeabilization of monolayers with saponin before staining restored a labelling
      pattern for NEP similar to the one obtained for DPP-IV. This suggests that
      although DPP-IV and NEP follow similar patterns of expression when enzymic
      activities are measured on whole-cell extracts, targeting of these brush-border
      proteins to the cell surface appears to be regulated in different ways.

PMID- 1361729
TI  - Widespread co-localization of mRNAs encoding the guanylate cyclase-coupled
      natriuretic peptide receptors in rat tissues.
AB  - Natriuretic peptides modulate vasorelaxation, diuresis, and natriuresis through
      the stimulation of cGMP production by the guanylate cyclase-coupled natriuretic
      peptide receptors, GC-A and GC-B. We used reverse transcription-polymerase chain
      reaction to determine the distribution of mRNA encoding both receptors in rat
      tissues. GC-A and GC-B transcripts were detected in all peripheral and neural
      tissues examined. Since the atrial natriuretic peptide gene is expressed in all
      these tissues, our widespread detection of GC-A and GC-B mRNAs now suggests that
      natriuretic peptides may act as endocrine and paracrine hormones as well as
      neurotransmitters via both GC-A and GC-B receptors.

PMID- 1361730
TI  - Site-directed mutagenesis of conserved residues of Clostridium thermocellum
      endoglucanase CelC.
AB  - Four conserved residues of Clostridium thermocellum endoglucanase CelC were
      replaced by site-directed mutagenesis. Proteins mutated in His-90, Asn-139 and
      Glu-140 showed strongly reduced activity, in agreement with predictions of
      sequence alignments. Mutations in Glu-140 did not result in any detectable change
      in Km, or apparent size, suggesting that Glu-140 is directly involved in
      catalysis. The pH optimum of the proteins carrying the Glu-140/Ala and Glu140/Gln
      mutations was lower than that of the wild type, whereas the activity vs. pH
      profile of Glu-140/Asp CelC was similar to that of the wild type, suggesting that
      Glu-140 may act as a proton donor.

PMID- 1361731
TI  - Marked association of a RFLP for the low density lipoprotein receptor gene with
      obesity in essential hypertensives.
AB  - RFLPs at the low density lipoprotein receptor locus (LDLR) display marked linkage
      disequilibrium between each other. Cross-sectional analysis of a bi-alleleic
      ApaLI RFLP of LDLR showed that the 9.4- and 6.6-kb alleles were present in
      similar frequency between a group of 84 Caucasian essential hypertensive (HT) and
      a group of 96 normotensive subjects whose parents each had a similar blood
      pressure status at age > or = 50. After subdividing HTs into lean and obese,
      however, the frequency of the 6.6-kb allele in the 27 HTs with BMI > or = 26
      kg/m2 was 0.63, compared with 0.39 for HTs with BMI < 26 (chi 2 = 8.8; P =
      0.004). The difference in genotype frequencies was even more striking (chi 2 =
      23; P = 0.00008), with a virtual absence of 9.4-kb homozygotes in the obese HT
      group (1 vs 22). Genetic variation at LDLR (19p13.2) is thus associated with
      obesity in HT.

PMID- 1361732
TI  - Modulation of multidrug resistance gene expression in rat hepatocytes maintained
      under various culture conditions.
AB  - P-glycoprotein (P-gp), the multidrug resistance gene product, is overexpressed in
      normal adult rat hepatocytes under standard culture conditions. We have studied
      the modulation of P-gp expression in this in vitro model in the presence of both
      epidermal growth factor and pyruvate, which favor hepatocyte growth, as well as
      in the presence of either dimethyl sulfoxide (DMSO) or nicotinamide, which favors
      maintenance of differentiated functions. P-gp overexpression, estimated by
      northern blotting and doxorubicin-mediated drug efflux analyses, was similarly
      observed during culture in both standard and proliferating conditions, while it
      was delayed, but not inhibited, in the presence of DMSO or nicotinamide. These
      results suggest that the functional P-gp overexpression occurring in rat
      hepatocytes when exposed to an unfamiliar environment is at least partly not
      related to cell proliferation or the degree of cell differentiation in vitro.

PMID- 1361733
TI  - Pharmacological characterization of a beta 3-receptor agonist (BRL 37,344) and a
      partial agonist (CGP 12,177A) in neonatal rat liver plasma membranes.
AB  - The pharmacological properties of BRL 37,344 (sodium-4-(2'-[2-hydroxy-2- (3
      chloro-phenyl)ethylamino]-propyl)phenoxyacetatesesquihydrate), a beta 3-selective
      agonist, and CGP 12,177A) (-)-4-(3-t-butyl amino-2-hydroxypropoxy) benzimidazole
      2-one], a non-selective beta-antagonist, recently characterized as a partial beta
      3-agonist in rat adipose tissue, were studied in comparison with isoproterenol, a
      non-selective beta-agonist, in plasma membranes prepared from the livers of
      newborn rats. Competition binding curves obtained with [125I]iodocyanopindolol
      ([125I]CYP) as ligand and isoproterenol or BRL 37,344 as competitor were
      characterized by the presence of a high and a low affinity binding site; the high
      affinity binding site was no longer detectable when guanidylimidobisphosphate
      (GppNHp) was present in the incubation mixture. Competition curves with CGP
      12,177A were monophasic and independent of GppNHp. In the presence of 10(-7) M of
      the beta 2-selective antagonist ICI 118,551 [erythro-(+/-)-1-(7-methylindan-4
      yloxy)-3-isopropylamino butan-2-ol], a concentration which blocks most of the
      beta 2-receptors, ligand binding was reduced to 32% of its maximum. Under these
      conditions, isoproterenol further displaced the ligand, and competition curves
      still displayed the high and the low affinity binding sites; BRL 37,344, however,
      caused no further displacement of ligand, except at the highest concentrations.
      This suggests that BRL 37,344 occupies only the ICI 118,551-sensitive binding
      sites, i.e. beta 2-receptors. Isoproterenol and BRL 37,344 both stimulated
      adenylate cyclase (EC 4.6.1.1) activity concentration dependently, although the
      stimulating effect of BRL 37,344 was about half of what was found for
      isoproterenol. Furthermore, BRL 37,344 inhibited concentration dependently the
      isoproterenol-induced stimulation of adenylate cyclase, and the inhibition was
      dependent on the concentration of isoproterenol. The stimulating effect of
      isoproterenol and BRL 37,344 on adenylate cyclase was blocked by ICI 118,551,
      whereas the beta 1-selective antagonist CGP 20,712A ((+/-)-(2-(3-carbamoyl-4
      hydroxyphenoxy)-ethylamino)-3-[4-(1-methy l-4- trifluoromethyl-2-imidazolyl)
      phenoxy]-2-propanolmethane sulphonate) was ineffective. CGP 12,177A failed to
      stimulate adenylate cyclase activity. From these results we suggest that BRL
      37,344 acts as a beta 2-partial agonist in rat liver. The results obtained with
      CGP 12,177A are typical for a non-selective beta-antagonist. We therefore
      conclude that there is no pharmacological evidence for the presence of beta 3
      receptors in livers from newborn rats.

PMID- 1361734
TI  - The development of monoclonal antibodies to the human mitochondrial 60-kd heat
      shock protein, and their use in studying the expression of the protein in
      rheumatoid arthritis.
AB  - OBJECTIVE: To assess the claim that the human 60-kd heat-shock protein (HSP) is
      highly expressed in the joints of patients with rheumatoid arthritis (RA), but is
      not readily detected in normal tissues. METHODS: Monoclonal antibodies were
      raised against the human 60-kd mitochondrial heat-shock protein (P1 protein;
      hsp60), and their specificity was established. They were then applied to synovial
      tissue. RESULTS: HSP was expressed similarly in normal, osteoarthritic, and RA
      synovium. Low levels of hsp60 were detected in synovial fluid by
      immunoprecipitation. CONCLUSION: Minor differences in the distribution of hsp60
      in synovium from RA joints were attributable to increased cellularity and to the
      disorganization of the tissue architecture.

PMID- 1361735
TI  - Effect of nipradilol on cardiovascular hemodynamics during exercise in angina
      pectoris with old myocardial infarction.
AB  - Nipradilol (3,4-dihydro-(2-hydroxy-3-isopropylamino)-propoxy-3-nitroxy-2H-1-
      benzopyran, K-351, CAS 81486-22-8) is a new type of beta-blocker with
      vasodilating action. The effect of nipradilol on hemodynamics at rest and during
      exercise with a multi-stage bicycle ergometer in supine position was studied in 8
      male patients suffering from angina pectoris with old myocardial infarction.
      Nipradilol was orally given at the daily dose of 12 mg (b.i.d.) for one week, and
      various hemodynamic parameters were measured at rest and during exercise before
      and after the treatment with nipradilol. At rest, the blood pressure was almost
      unchanged, heart rate was significantly reduced, cardiac output tended to
      decrease, and the pulmonary blood pressure and left ventricular ejection fraction
      (EF) were almost unchanged. At peak exercise, the blood pressure tended to
      decline, heart rate was significantly reduced, cardiac output tended to decrease
      and the pulmonary blood pressure and EF increased significantly. Consequently,
      the antianginal effect of nipradilol is considered to be attributable to the
      reduction in myocardial oxygen consumption caused by a decrease in double
      product. It is thus suggested that nipradilol exerts its antianginal effect
      without adversely affecting the cardiac performance.

PMID- 1361736
TI  - Effect of a new non-steroidal anti-inflammatory combination of a histamine H2
      antagonist and indomethacin on gastroduodenal mucosal membrane in rat.
AB  - The new non-steroidal anti-inflammatory drug (NSAID), N-(3-[3-(piperidinyl
      methyl) phenoxy] propyl)-carbamoyl-methylthio]ethyl 1-(p-chlorobenzoyl) 5-methoxy
      2-methyl-3-indolyl-acetate (CP 331, CAS 127966-70-5), a compound with a structure
      of an ester combining indomethacin (IM) and a histamine H2 antagonist, has been
      reported to have anti-inflammatory, analgesic and antipyretic effects. However,
      the influence of CP-331 on the gastroduodenal mucosa was not fully investigated.
      Therefore this study was undertaken to investigate the effect of CP-331 on the
      gastroduodenal mucosa membrane in rats. After single oral drug administration,
      the UD50 value (50% ulcerogenic dose) of CP-331 calculated from the incidence
      rate of gastric ulcer was higher than 1000 mg/kg; that for IM was 5.2 mg/kg.
      Moreover it was examined whether CP-331 had a preventive effect on NSAID-induced
      gastric damage. The results showed that the co-administration of CP-331 10-30
      mg/kg prevented significantly the acute gastric mucosal injury caused by IM
      administration (20 mg/kg). CP-331 with anti-inflammatory activity does not cause
      gastric injury, moreover, because of its preventing and therapeutic effects on
      the damage to gastric mucous membrane induced by IM, CP-331 might be useful in
      the treatment of gastropathy caused by NSAID in clinic.

PMID- 1361737
TI  - Inhibition of HSV-1-specific cytotoxic T lymphocytes by recombinant-derived gp120
      of HIV-1.
AB  - The ability of human immunodeficiency virus type-1 (HIV-1) and recombinant HIV-1
      gp120 to prevent target cell lysis by herpes simplex virus type 1 (HSV-1)
      specific cytotoxic T lymphocytes (CTL) was assessed by limiting dilution
      analysis. Live and inactivated HIV-1 as well as recombinant-derived gp120 all
      substantially inhibited HSV-1-specific CTL. Soluble CD4 antigen reversed the
      inhibition by gp120 when simultaneously added with gp120 to the assay. In
      addition, the monoclonal anti-CD4 antibody a-Leu3a mimicked the effects of gp120
      in these experiments. These data suggest that the observed decrease in measurable
      CTL activity is caused by direct or steric hindrance of the CD4-class II major
      histocompatibility complex interaction between the effector and target cells.

PMID- 1361739
TI  - Impairment of learning by localized injection of an N-methyl-D-aspartate receptor
      antagonist into the hyperstriatum ventrale of the domestic chick.
AB  - A restricted part of the domestic chick forebrain is critically involved in the
      learning process of imprinting. This region is the intermediate and medial part
      of the hyperstriatum ventrale (IMHV). The effect on imprinting of local injection
      of the N-methyl-D-aspartate (NMDA) receptor blocker D-amino-5-phosphonopentanoic
      acid (D-AP5) into the left IMHV was studied in chicks in which the right IMHV had
      been lesioned. The left IMHV is essential for imprinting when chicks have been
      lesioned in this way. Injection of approximately 0.7 nmol D-AP5 into the left
      IMHV significantly impaired imprinting. Injection of approximately 0.2 nmol D-AP5
      into the left IMHV, or of approximately 0.7 nmol D-AP5 into the left
      hyperstriatum accessorium, was without significant effect on imprinting. These
      results suggest that NMDA receptors in the left IMHV may play an important part
      in this learning process.

PMID- 1361738
TI  - Modulation of gene function by retinoic acid.

PMID- 1361740
TI  - Effect of ethanol on ascorbate release in the nucleus accumbens and striatum of
      freely moving rats.
AB  - An in vivo voltammetry technique was used to monitor the extracellular ascorbate
      (AA) concentration in the nucleus accumbens and striatum of unanesthetized,
      freely moving rats. A single injection of ethanol, 1.0 g/kg intraperitoneally
      (IP), induced a significant increase in extracellular AA concentration in both
      the nucleus accumbens and striatum. This effect was dose dependent within a dose
      range from 0.5-2.0 g/kg. 4-Methylpyrazole (50 mg/kg, IP), which inhibits
      alcoholdehydrogenase, could not prevent the increase in AA concentration, evoked
      by ethanol. Furthermore, systemic administration of acetaldehyde (20 mg/kg, IP),
      the main metabolite of ethanol, did not have any effect on the level of AA in the
      nucleus accumbens or striatum. These results show that ethanol can alter the
      brain extracellular AA levels and that this effect seems to be attributed to
      ethanol itself and not to acetaldehyde. Consequently, these results indicate that
      a role for AA in the action of ethanol in the brain should be considered.

PMID- 1361741
TI  - Subthalamic nucleotomy alleviates parkinsonism in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-exposed primate.
AB  - Research into the neural mechanisms underlying the symptoms of parkinsonism
      utilizing the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-exposed primate
      model have shown that the subthalamic nucleus (STN) occupies a central role. As a
      logical development of this theory, we have studied the effects of
      thermocoagulative lesions of the STN in the primate model. Such lesions can cause
      remarkable symptom reversal in the experimental primate model.

PMID- 1361742
TI  - Large diurnal variation in CD4 cell count and T-cell function among drug users:
      implications for clinical practice and epidemiological studies.
AB  - OBJECTIVE: To measure diurnal variation in the CD4 cell count and T-cell
      reactivity of drug users. DESIGN: A prospective epidemiological study among HIV
      infected and non-infected drug users attending the Municipal Health Service of
      Amsterdam, The Netherlands. PATIENTS: Eleven HIV-infected and seven non-infected
      drug users. MAIN OUTCOME MEASURES: CD4 cell counts and T-cell reactivity three
      times a day. T-cell subsets and T-cell reactivity were determined from blinded
      samples within 2 hours. RESULTS: The number of CD4 cells increased by 130 x
      10(6)/l (P < 0.05) in HIV-infected intravenous drug users over 8 hours. Following
      stimulation with anti-CD3 monoclonal antibodies, the T-cell reactivity of HIV
      infected drug users rose from 118 to 221 c.p.m. (P < 0.01) over 8 hours. CD4 cell
      counts of the total study population increased by 37% and T-cell reactivity by
      93%. The increase in the number of CD4 cells was more marked among active drug
      users than among drug users who had not used drugs recently. CONCLUSION:
      Variation in the CD4 cell count and in T-cell reactivity is large among drug
      users.

PMID- 1361743
TI  - A novel coculture system for evaluating anti-HIV drugs.
AB  - OBJECTIVE: To develop a useful system for evaluating novel anti-HIV drugs.
      DESIGN: The activity of most antiviral compounds in cell-free HIV infection
      systems has been evaluated. However, the inhibitory effects on both the process
      of HIV induction and viral dissemination to uninfected cells have not been fully
      investigated. We have therefore developed a new cocultivation system using
      chronically HIV-infected monocytes and CD4+ T-lymphocytes in the presence of
      tumor necrosis factor (TNF). METHODS: We designed a cocultivation system using
      flow cytometry with U1 cells and Molt-4 cells in the presence of TNF. The
      antiviral activities of several compounds in the cocultivation system and other
      assay systems were compared. RESULTS: Only pradimicin A and glycyrrhizin showed
      strong inhibitory activity in the cocultivation system in the presence of TNF,
      whereas dextran sulfate, curdlan sulfate and N-acetylcysteine exhibited moderate
      or weak inhibitory activity in the system. 3'-azido-2',3'-dideoxythymidine and
      2',3'-dideoxyadenosine were completely ineffective in the system. CONCLUSION:
      These results support the suggestion that our cocultivation system includes HIV
      induction in chronically infected monocytes, and the resulting cell-to-cell
      infection between HIV-infected monocytes and Molt-4 cells or Molt-4 cells and
      their HIV-converted counterparts. Our new cocultivation system may constitute a
      useful tool in the identification of novel anti-HIV compounds.

PMID- 1361744
TI  - Methods for detecting early signs of AIDS dementia complex in asymptomatic HIV-1
      infected subjects.
AB  - OBJECTIVES: To determine the optimal diagnostic procedures for identifying early
      signs of AIDS dementia complex (ADC) in asymptomatic HIV-1-infected individuals,
      in order to prevent further cognitive function impairment by early treatment.
      DESIGN: Study patients had been referred electively and consecutively to
      hospital; all had been referred for the first time and gave informed consent.
      Inclusion criteria were (1) lack of history and/or symptoms of psychosis and
      neurological disorders; (2) lack of active viral, protozoan or fungal pathology;
      (3) abstinence from heroin and/or cocaine for at least 6 months before baseline
      evaluation. SETTINGS: Subjects were seen at the L. Spallanzani Hospital for
      Infectious Diseases, Rome, Italy between March 1989 and March 1991. PARTICIPANTS:
      Eighty-two asymptomatic HIV-1-infected subjects: 41 drug users, 27 homosexuals
      and 14 heterosexuals. MAIN OUTCOME MEASURES: All subjects were evaluated using
      Wechsler-Bellevue I, Benton C form and Bender tests. Thirty-nine subjects
      underwent single-photon emission computed tomography (SPECT) and 12 magnetic
      resonance imaging (MRI). The immunological status of each subject was determined.
      RESULTS: On psychometric testing, 23 out of the 82 (28%) asymptomatic subjects
      had a mental decay percentage (MD%) > or = 20%. Cerebral perfusion abnormalities
      were detected in 31 out of 39 (79.48%) subjects who underwent SPECT; MRI
      abnormalities were observed in seven out of 12 (58%) subjects. Twelve out of 23
      subjects with MD% > or = 20, 15 out of 29 subjects with SPECT abnormalities and
      four out of seven patients with MRI abnormalities had total CD4+ lymphocyte
      counts > or = 500 x 10(6)/l. CONCLUSIONS: The high incidence of abnormal SPECT
      and of MD% > or = 20 in asymptomatic HIV-1-infected patients, and the lack of
      correlation between immunological status and degree of mental decay, SPECT and
      MRI abnormalities raise many questions about subclinical HIV-1 neurological
      disease.

PMID- 1361745
TI  - Relationship between herpes simplex virus ulceration and CD4+ cell counts in
      patients with HIV infection.
AB  - OBJECTIVE: To establish the incidence of herpes simplex virus (HSV) ulceration in
      relation to CD4+ cell counts in HIV-infected patients. DESIGN: Swabs were taken
      from all ulcerated lesions in HIV-infected patients and cultured for HSV. CD4+
      cell counts were performed at regular intervals. SETTING: The HIV unit at a
      London teaching hospital (the Royal Free Hospital, London, UK). PATIENTS: All HIV
      infected patients (n = 500) attending the HIV unit. RESULTS: Two hundred and
      twenty-three swabs were obtained from 118 patients; 83 (37.2%) swabs from 62
      (52.5%) patients were positive for HSV. Of 96 swabs taken from patients with CD4+
      cell counts < 50 x 10(6)/l, 56 (58.3%) were positive for HSV, compared with 27 of
      127 (21.2%) swabs from patients with higher CD4+ cell counts (P < 0.0001). Of
      patients with CD4+ cell counts < 50 x 10(6)/l, 37 of 47 (78.7%) had positive
      cultures compared with 25 of 71 (35.2%) of patients with higher counts (P <
      0.0001). This trend was observed with swabs from all body sites; sufficient
      samples were available from oral and perianal lesions to demonstrate statistical
      significance (P < 0.0001 and P = 0.007, respectively). CONCLUSIONS: These results
      show a sharp rise in the incidence of HSV with CD4+ cell counts < 50 x 10(6)/l
      and thus provide important data for the design of studies of anti-HSV
      prophylaxis. Furthermore, since nearly 60% of all ulcers in patients with such
      low CD4+ counts are HSV-positive, we suggest appropriate empirical therapy on
      presentation.

PMID- 1361746
TI  - Maintenance of CD4+ cells by thymopentin in asymptomatic HIV-infected subjects:
      results of a double-blind, placebo-controlled study.
AB  - OBJECTIVE: To assess the efficacy and safety of thymopentin in HIV-infected
      patients who had not yet developed AIDS. DESIGN: Patients were stratified into
      asymptomatic or symptomatic groups and randomized to receive either thymopentin
      (50 mg) or placebo, subcutaneously, double-blind for 24 or 52 weeks, three times
      a week. SETTING: Patients were enrolled at three sites (two hospital clinics and
      one private practice). PATIENTS: Of 91 HIV-seropositive patients (52 asymptomatic
      and 39 symptomatic) from whom HIV could be isolated from peripheral blood, 45
      were enrolled for 24 weeks and 46 for 52 weeks of double-blind evaluation. MAIN
      OUTCOME MEASURES: Virological, immunological and clinical evaluations were
      performed before and during treatment. RESULTS: Thymopentin-treated asymptomatic
      patients had more CD4+ cells, as demonstrated by a greater area under the
      percentage CD4+ cells curve (P = 0.03) and a shorter median time to a 20%
      increase in percentage of CD4+ cells (P = 0.04) in the first 24 weeks, with
      similar trends in the 52-week study. By 24 weeks no asymptomatic thymopentin
      treated and two placebo-treated patients (9.1%, Kaplan-Meier estimate) had
      progressed to constitutional symptoms (P = 0.12; two-tailed Wilcoxon-Gehan test),
      with only one further progression in a placebo-treated patient in the subset
      followed for 52 weeks. Symptomatic patients receiving thymopentin or placebo were
      similar in both CD4+ cell levels and disease progression (two progressions to
      AIDS in each group). No serious adverse effects attributable to thymopentin were
      observed. CONCLUSIONS: These results, if confirmed, indicate that thymopentin, by
      maintaining CD4+ cells, could slow or arrest immune decline and consequent
      disease progression at the asymptomatic stage of HIV infection.

PMID- 1361748
TI  - Prognostic value of an elevated CD8 lymphocyte count in HIV infection. Results of
      a prospective study of 152 asymptomatic HIV-positive individuals.
AB  - OBJECTIVE: To evaluate the prognostic value of an elevated CD8 lymphocyte count
      in the early stages of HIV infection. DESIGN: A prospective study ongoing since
      January 1986. METHODS: One hundred and fifty-two asymptomatic HIV-positive
      individuals with a CD4 lymphocyte count > 400 x 10(6)/l at enrollment were
      included. Disease progression was defined as a CD4 count < 200 x 10(6)/l.
      RESULTS: During the follow-up period, CD4 count decreased in 33 individuals; CD8
      count increased to > 1500 x 10(6)/l in 38 individuals and doubled in 35. The risk
      of a decreasing CD4 count was estimated to be 1.7-fold higher, although not
      significantly so, after the elevation of the CD8 count to > 1500 x 10(6)/l than
      before or in the absence of such an increase. However, this predictive value
      disappeared when five baseline parameters found to predict the outcome
      (neopterin, beta 2-microglobulin, p24 antigen, anti-p18 antibody and
      immunoglobulin A) were adjusted. CONCLUSION: Elevated CD8 count appears to be a
      weak marker for disease progression.

PMID- 1361747
TI  - Differences in laboratory values in HIV infection by sex, race, and risk group.
AB  - OBJECTIVES: To determine differences in CD4+ and CD8+ lymphocyte values, beta 2
      microglobulin (beta 2M), and HIV p24 antigenemia by sex and race among HIV
      seropositive and HIV-seronegative injecting drug users (IDU), and to compare
      these values with those in homosexual men of equivalent status. DESIGN: Baseline
      values from a cohort of 206 HIV-seropositive and 173 HIV-seronegative IDU were
      compared with values from a cohort of 288 HIV-seropositive homosexual men and 176
      HIV-seronegative controls, who were prospectively followed at 6-month intervals,
      to examine differences in laboratory values in HIV-infected individuals by sex,
      race, and risk group. METHODS: Among HIV-seropositives, we compared white and
      black IDU only (n = 167), and white male IDU (n = 38) with white homosexual men
      (n = 256). Laboratory values from the cohort of homosexual men at 24, 36 and 48
      months of follow-up were compared with IDU values. RESULTS: HIV-infected female
      IDU had significantly higher CD4+ lymphocyte counts (P < 0.03) and percentages of
      CD4+ lymphocytes (P < 0.004) than male IDU, resulting in higher CD4:CD8 ratios (P
      < 0.002). White IDU had significantly higher serum beta 2M levels than black IDU
      (P < 0.02). Black female IDU were much less likely to be HIV p24-antigenemic (1%)
      than all other groups (P < 0.005). Compared with homosexual men, male IDU had
      significantly elevated beta 2M levels (0.58 mg/l higher). When controlled for
      CD4+ lymphocyte values as a surrogate for length of time HIV-infected, beta 2M
      and HIV p24 antigenemia differences persisted. CONCLUSIONS: These differences
      should be considered when HIV p24 antigen, CD4+ lymphocyte counts and beta 2M
      levels are used as surrogate markers in clinical trials and management of HIV
      disease.

PMID- 1361749
TI  - Studies of prognostic markers in HIV infection: implications for pathogenesis.

PMID- 1361750
TI  - Short-term evaluation of zidovudine-treated patients: decrease in plasma and
      cellular viraemia titres.

PMID- 1361751
TI  - Trends in zidovudine prescription since 1987 in AIDS-free HIV-positive French
      patients attending university hospitals.

PMID- 1361752
TI  - The fragile-X syndrome after the discovery of the FMR-1 gene. The clinical
      geneticist faced with the unravelled enigmas and persisting difficulties in
      genetic counseling.

PMID- 1361753
TI  - Expression of the fragile-X in the "premutated"/"non-imprinted" state.
AB  - Data about the expression of the fragile site at Xq27.3 from 74 daughters of
      normal transmitting males (NTMs) were collected from 7 different genetic centers.
      The majority (85.1%) of these obligate female carriers did not show any
      cytogenetic expression of fra-X. The remaining 14.9% of these females had
      frequencies below 3%. In cases with a frequency below 3% of fra-X, a
      "premutated"/"non imprinted" state of a female carrier should be considered. The
      results of this collaborative study are in accordance with data from DNA studies
      taking the premutation model into account.

PMID- 1361754
TI  - Enzyme-linked immunosorbent assay for determination of antibodies to Vibrio
      cholerae toxin-coregulated pili.
AB  - An ELISA for determination of antibodies to V. cholerae TCP was developed. Since
      purified TCP preparations contained detectable amounts of LPS (as shown by ELISA
      and immunoelectron microscopy with anti-LPS polyclonal serum), a capture ELISA
      was used. In this test the plate was coated with anti-TCP monoclonal antibody
      followed by incubation with TCP fimbriae. By this procedure no LPS bound to the
      solid phase as shown by the loss of reactivity with anti-LPS serum. The capture
      ELISA allowed sensitive and specific determination of TCP antibodies in sera of
      rabbits immunized with classical but not El Tor V. cholerae strains. There was
      good agreement between results in the TCP ELISA and reactivity with the TcpA band
      in immunoblot analyses when antisera raised against classical and El Tor vibrios
      were studied.

PMID- 1361755
TI  - Expression of proliferative cell nuclear antigen (PCNA) in urinary bladder
      carcinoma. Evaluation of antigen retrieval methods.
AB  - Proliferative cell nuclear antigen (PCNA) expression was analyzed in formalin
      fixed and paraffin-embedded specimens from patients with urinary bladder cancer
      using three different anti-PCNA monoclonal antibodies. In 20 recent cases a
      positive correlation was found between the extent and intensity of PCNA staining
      and grade of malignancy. In 95 specimens, three to six years old, extensive
      positive staining was detected in 15 and 23% of grade 2B and 3-4 tumors,
      respectively. No equivalent staining was found in the grade 1 and 2A tumors. In
      material more than six years old, a remarkably weak staining was observed
      regardless of grade. Similarly, in a test of archival material of tonsils a very
      weak immuno-reactivity was found as compared with fresh material. However,
      antigen retrieval by microwave heating of the tissue sections was possible in the
      majority of all cases, and the difference in extent and intensity of the staining
      between low and high grade tumors remained.

PMID- 1361756
TI  - Washington declaration on AIDS education.

PMID- 1361757
TI  - CD45 phosphotyrosine phosphatase and p56lck protein tyrosine kinase: a functional
      complex crucial in T cell signal transduction.
AB  - Tyrosine phosphorylation of several intracellular proteins is observed very early
      during T cell activation. p56lck, a non-receptor src-like protein tyrosine kinase
      (PTK) which is associated with the intracellular domains of CD4 and CD8 co
      receptors, has been implicated in these early signal transduction events.
      Furthermore, recent experiments indicate that the receptor phosphotyrosine
      phosphatase, CD45, might be important in the regulation of p56lck PTK activity
      and that its expression is required for the generation of second messenger
      molecules following TCR triggering. Here, using co-capping experiments and double
      indirect immunofluorescence microscopy in functional human T lymphocytes, a
      specific co-distribution of a significant fraction of p56lck with CD45, but not
      with several other cell surface proteins, has been revealed. This is the first
      demonstration of a physical interaction between a receptor phosphotyrosine
      phosphatase and a PTK under physiologically relevant conditions. In addition,
      after antibody-induced capping of CD4, both a co-localization of p56lck and CD4,
      and concomitantly a significant increase in intracellular phosphotyrosine at the
      sites of CD4 caps were observed. In strong contrast to these results, co
      clustering of CD4 with CD45 did not result in any detectable intracellular
      phosphotyrosine at the cap sites. These data indicate that CD45 can act on CD4
      associated phosphoproteins in viable human T lymphocytes. Further, this provides
      evidence that p56lck PTK is a substrate of CD45 phosphotyrosine phosphatase in
      vivo and thereby supports the idea that CD45 is an early regulator of T cell
      activation involved in the modulation of the coupling of receptor-triggered
      events to intracellular signalling pathways.

PMID- 1361759
TI  - Selected papers from the 12th Annual Conference on Peritoneal Dialysis. Seattle,
      Washington, February 19-21, 1992.

PMID- 1361758
TI  - Analysis of the steady-state and initial rate of doxorubicin efflux from a series
      of multidrug-resistant cells expressing different levels of P-glycoprotein.
AB  - Continuous monitoring of fluorescence (CMF) has been used to examine doxorubicin
      efflux from intact human myeloma cells. The time resolution of these measurements
      has enabled detailed comparison of the initial rates of efflux for the drug
      sensitive myeloma line RPMI 8226 and a series of sequentially derived multidrug
      resistant (MDR) lines expressing different amounts of human MDR protein (P
      glycoprotein). Cells that are 3-, 10-, 60-, or 120-fold resistant to doxorubicin
      export approximately 10, 20, 30, or 33% more doxorubicin than the parental
      sensitive cells, respectively, when all are preloaded to the same level of total
      intracellular drug. Remarkably, however, when cells are loaded to the same level
      of exchangeable drug the initial rates of efflux are found to be virtually
      identical. This agreement between rates is apparently not dependent on the drug
      concentration. Approximately 50% of the increase in the steady-state level of
      doxorubicin efflux for the resistant cells is abolished upon glucose starvation.
      However, surprisingly, the apparent initial rates of efflux from the treated and
      untreated cells are found to be virtually the same. Pretreatment of the resistant
      cells with verapamil reduces the steady-state level of efflux but increases the
      apparent initial rate at some concentrations. Conversely, vincristine does not
      alter steady state but slows the initial rate of efflux from both sensitive and
      resistant cells by approximately the same extent. Finally, quite interestingly, a
      nearly linear relationship between pHi and relative steady state of efflux is
      found for the series of cell lines. These data are interpreted in terms of
      existing models for MDR.

PMID- 1361760
TI  - Failure of CAPD patients to respond to an oral iron absorption test.
AB  - CAPD patients require supplemental iron to maintain a response to erythropoietin.
      Because of limited availability of parenteral iron dextran, oral iron must be
      used. However, oral iron may not be effective in most dialysis patients. To
      determine if oral iron is well absorbed, a modified oral iron absorption or
      tolerance test was performed in CAPD patients using two oral iron preparations.
      Serum irons were measured at baseline in a fasting state and repeated two hours
      after the ingestion of 325 mgs ferrous sulfate in five CAPD patients. In
      addition, eight patients had serum irons determined before and two hours after
      taking liquid oral ferrous fumarate in capsule form. Healthy controls were
      compared with each group. All five patients who received ferrous sulfate had
      borderline to low normal serum iron and iron stores. Average increase in serum
      irons was only 19 mcg/dl in patients compared to 52 mcg/dl in controls. Patients
      receiving ferrous fumarate rose only 14 mcg/dl compared to 60 mcg/dl in controls.
      We conclude that oral iron is poorly absorbed in most CAPD patients and that the
      oral iron absorption test may be helpful in identifying patients who are
      effective iron absorbers. Unfortunately, until parenteral iron dextran is readily
      available, oral iron therapy is the only alternative for iron supplement. The
      oral iron absorption test may predict who will respond to oral iron in the long
      term.

PMID- 1361761
TI  - Single center success with a high risk peritoneal dialysis population.
AB  - A large end stage renal failure population treated by chronic ambulatory
      peritoneal dialysis (CAPD) was examined for rates of infection, CAPD modality
      failure and patient survival (N = 347). Nearly half were considered high risk for
      survival for reasons of age (39% older than 60 years), diabetes mellitus (33%),
      hemodialysis access failure (10%), poor cardiopulmonary reserve (16%) or
      technical challenges (30% had morbid obesity, history of abdominal aortic
      aneurysm repair or multiple abdominal surgeries). Hence, CAPD was often initiated
      by default rather than choice in the 347 patients studied (mean age: 51 +/- 17
      years). Infections greatly outnumbered technical failures as grounds for
      cessation of CAPD. Over 5521 patient-months, 51% of patients developed infection
      with peritonitis predominating (80%) when compared to exit site infections (20%).
      The frequency of infections was 1.9 mean episodes per patient; however, 55% of
      these patients had only one episode of peritonitis. A rate of 0.75 infections per
      patient per year was seen with an average interval of 16 months between
      infections. Technique and patient survival rates at 4 years were 50% and 61%
      respectively. High risk status does not preclude successful CAPD and should not
      preclude its implementation.

PMID- 1361762
TI  - Routine measurement of hydrostatic intraperitoneal pressure.
AB  - A simple, non-invasive and well-tolerated technique for routine measurement of
      intraperitoneal hydrostatic pressure (IPP) in patients treated with peritoneal
      dialysis (PD) is presented. The height of the dialysis fluid in the PD line was
      measured, under atmospheric pressure, before drainage and during inspiration
      (IPPinsp) and expiration (IPPexp), taking the axillary line as the reference
      point of the resting subject in strict supine position. Normal values were
      established for a population of 18 patients treated with PD for 19.8 +/- 20.9
      months under clinical and biological stable conditions. For an intraperitoneal
      volume of 2,820 +/- 419 ml, IPPinsp = 14 +/- 2 cmH2O; IPPexp = 12 +/- 2 cmH2O;
      IPP mean (defined as (IPPinsp+IPPexp)/2) = 13 +/- 2 cmH2O; IPP (defined as
      IPPinsp - IPPexp) = 2 +/- 2 cmH2O. IPP could not predict mechanical complications
      (hernia, hemorrhoids, dialysis fluid leakage) but the maximal IPPexp clinically
      tolerated was 20 cmH2O.

PMID- 1361763
TI  - Chondroitin sulphate and peritoneal permeability.
AB  - We studied the effect of chronic intraperitoneal (ip) infusion of saline
      supplemented with the glycosaminoglycan-chondroitin sulphate 0.1% on the
      permeability and peroxidation of the peritoneal membrane in rats and compared
      this with the effect of saline infusion alone. Animals treated with chondroitin
      sulphate had a higher net ultrafiltration (uf), a slower glucose absorption from
      the dialysate and less trans-peritoneal loss of proteins. Chronic ip infusion of
      chondroitin sulphate reduced peroxidation of the peritoneum. These observations
      suggest that chondroitin may effect the peritoneal interstitium-an important
      barrier of fluid and solutes transport.

PMID- 1361764
TI  - Low protein catabolic rate and serum albumin correlate with increased mortality
      and abdominal complications in peritoneal dialysis patients.
AB  - We retrospectively reviewed 167 consecutive peritoneal dialysis patients with
      regard to serum albumin (Alb), mortality and abdominal complications. In
      addition, 25 patients were studied with serial measurements of urea kinetics. The
      patients were divided into four groups based on their dialysis index (DI) and
      normalized protein catabolic rate (NPCR) (Table I). 12/167 patients were
      identified with abdominal catastrophes. Before these complications occurred, the
      M Alb in this group was 2.67 + 0.24 (compared to age, sex and disease matched
      controls of 3.55 + .11 P < .05). Six of these patients died from abdominal
      complications. In the 26 patients with serial urea kinetic studies, 4/11 patients
      in group IV died (low NPCR and low DI) (P < .05 compared to Group I, II or III).
      We conclude that urea kinetic modeling is predictive of outcome in those patients
      with presumed poor nutrition and inadequate dialysis and that abdominal
      catastrophes are more common in those patients with poor nutrition. Prospective
      interventional studies should be designed in an attempt to improve the poor
      outcome in this group of patients.

PMID- 1361765
TI  - Remarkable improvement of activity by CAPD in a hemodialysis patient with a
      pseudotumor of the craniocervical junction.
AB  - Pseudotumor of the craniocervical junction and destructive spondyloarthropathy
      (DSA) are the most serious forms of dialysis amyloidosis (DAA). Pain and
      paralysis due to these lesions significantly impair activity of a patients' daily
      life (ADL). CAPD improved ADL of a 54 year-old male patient complicated with
      various forms of DAA after 17 years of hemodialysis (HD) treatment. He was first
      diagnosed as having carpal tunnel syndrome 12 years after initiation of
      hemodialysis followed by dialysis shoulders(12 years), trigger fingers(12 years),
      bone cysts(15 years), tendon ruptures(17 years), DSA and a pseudotumor of the
      craniocervical junction(17 years). Magnetic resonance imaging (MRI) taken in May
      1989 revealed a pseudotumor of the craniocervical junction, which was 30 mm in
      diameter, located in front of partially destroyed C1 and C2. Neck pain and muscle
      weakness rendered him bed ridden. Six months after switching to CAPD with
      administration of prednisolone, neck pain disappeared. He recovered the muscle
      power by physical rehabilitation. At last it became possible for him to perform
      the CAPD procedure by himself and drive a car to the hospital as an out patient.
      In such cases of pseudotumors of the craniocervical junction, CAPD is one of the
      best methods for relieving the pain and muscle weakness.

PMID- 1361766
TI  - Adequacy of peritoneal dialysis: a review of quantitative and qualitative
      approaches.
AB  - This paper reviews the qualitative and quantitative approaches to assessing the
      adequacy of peritoneal dialysis. The quantitative measures reviewed include the
      KT/V urea index, the dialysis index, the weekly creatinine clearance, and the
      creatinine efficiency number. Studies that support as well as refute these
      measures are reviewed briefly. Many of these studies are retrospective analyses
      of longitudinal data in small numbers of patients or prospective cross-sectional
      studies. A prospective, longitudinal study involving large numbers of patients is
      required to resolve some of the controversies regarding the adequacy of
      peritoneal dialysis.

PMID- 1361767
TI  - Comparison of the efficacy cost and complication rate of APD and CAPD as long
      term outpatient treatments for renal failure.
AB  - We compared 10 patients treated with overnight APD in their homes with a parallel
      group of 30 patients having CAPD (Freeline II) over two years 1990 and 1991. Our
      aim was to discover if APD was an efficient and cost effective alternative to
      CAPD. The average amount of dialysate used per day in APD patients was 11 litres
      (range 9 to 14 litres) compared to 6.8 litres (range 6 to 10 litres) for CAPD.
      The average plasma creatinine was 920 umol/L, plasma urea of 21 mmol/L on APD and
      825 umol/L and 24 mmol/L respectively on CAPD. In 1990 there were 2 incidences of
      peritonitis (2 in 1991) in the APD patients compared to 24 incidences (24 in
      1991) in the CAPD patients with 6 recurrences (5 in 1991) and 19 exist site
      infections (24 in 1991). The average fluid costs plus disposables were
      comparable. However the cost of treating complications per patient for APD was
      for 1990 32 pounds (108 pounds in 1991) and for CAPD 832 pounds (1308 pounds in
      1991). All the APD patients who had previously experienced CAPD preferred this
      treatment for its convenience and social acceptability. APD is a cost-effective
      alternative to CAPD and has advantages in some patients.

PMID- 1361768
TI  - Quantitative and qualitative changes of serum albumin in CAPD patients.
AB  - This study was conducted to assess quantitative and qualitative changes in serum
      albumin in CAPD patients. For twenty-six CAPD patients as well as age-, sex- and
      dialysis history-matched HD patients, biochemical and physiological parameters
      including urea kinetics were determined. Albumin was qualitatively evaluated by
      HPLC. The CAPD patients showed significant decreases in serum albumin and the
      reduced form of albumin accompanied by a lower protein catabolic rate(PCR)
      compared to the HD patients. Thirty five % of CAPD patients showed mild to
      moderate hypoalbuminemia, associated with a higher incidence of peritonitis and
      longer hospital stay. Patients with hypoalbuminemia had less of the reduced form
      of albumin. A weak positive correlation was found between serum albumin
      concentration and KT/V, and PCR. Thus, in CAPD patients, there occur quantitative
      and qualitative changes in serum albumin. Hypoalbuminemia may be a risk factor
      for peritonitis and is due in part to insufficient dialysis and protein intake.
      Intermolecular change in albumin may possibly be due to uremia per se.

PMID- 1361769
TI  - Urea and creatinine generation and removal in a pregnant patient receiving
      peritoneal dialysis.
AB  - Peritoneal dialysis is the preferred form of dialysis during pregnancy because it
      is continuous and lacks the wide variation in chemistries, weight and blood
      pressure, and avoids the use of anticoagulation necessary during hemodialysis.
      This is a case report of a successful vaginal delivery of a 35 week healthy baby
      boy to a patient with end stage renal disease receiving peritoneal dialysis.
      Approximately one year after starting peritoneal dialysis for end stage renal
      disease of unknown etiology, this patient was noted to be pregnant during a
      transplant evaluation. BUN and creatinine generation increased with pregnancy. In
      order to keep the plasma BUN less than 50 mg/dl and creatinine less than 5 mg/dl,
      BUN and creatinine removal were increased by increasing the liters of dialysate
      from 8 liters to 16 liters per day. The peritoneal volume decreased from an
      initial 2 liters to 0.8 liter per exchange. The frequency of exchange increased.
      This was accomplished at home with a cycler so the patient was able to continue
      self care and maintain a quality of life. Peritoneal equilibration test during
      pregnancy did not change.

PMID- 1361771
TI  - Non-renal indications for peritoneal dialysis.
AB  - Peritoneal dialysis is rarely indicated for conditions other than end-stage renal
      failure. Patients with refractory congestive cardiac failure, who are awaiting
      cardiac transplantation or have potentially reversible cardiac disease, appear to
      benefit from CAPD. The prognosis of patients with fulminant hepatic failure or
      severe acute pancreatitis has not yet been shown to improve with the addition of
      peritoneal dialysis to standard supportive treatment. Isolated reports have
      suggested that patients with hypothermia, hyperthermia, dialysis-associated
      ascites and drug poisonings may be treated successfully with peritoneal dialysis.
      The above indications are encountered infrequently and renal failure remains the
      only major indication for commencing patients on peritoneal dialysis.

PMID- 1361770
TI  - Comparison of survival in CAPD and hemodialysis: a multicenter study.
AB  - We studied 1,622 patients who started regular dialysis treatment between 1985 and
      1989 in 19 centers from the Italian CAPD Study Group. There were 962 pts (59%)
      and on HD; 660 pts (41%) on CAPD. CAPD pts were older and had more risk factors
      at the start than HD pts (p < 0.0001). Overall patient survival was not
      statistically different between CAPD and HD at 6 years (42% CAPD; 54% HD).
      Multivariate analysis (Cox's model) on all population revealed that age and
      pretreatment risk factors had a statistically significant impact on patient
      survival (p < 0.0001), but not the type of dialytic treatment (CAPD or HD). When
      multivariate analysis was applied separately by treatment modalities, in HD group
      age and risk factors had the same negative influence on survival (p < 0.0001)
      while in CAPD group the influence of age on survival was less significant (p
      0.025). This multicenter study carried out with appropriate statistical methods
      in a large number of pts demonstrates that patients' survival at 6 years is not
      different on CAPD and HD (despite the worse patient selection on CAPD) and can be
      even better on CAPD for aged patients.

PMID- 1361772
TI  - Renal malignancy in peritoneal dialysis patients with acquired cystic kidney
      disease.
AB  - A known complication of long-term hemodialysis, acquired cystic kidney disease
      (ACKD) has been reported infrequently in association with chronic ambulatory
      peritoneal dialysis (CAPD). The duration of end stage renal failure (ESRF) is
      thought to correlate with the development of ACKD. Renal cell carcinoma has been
      reported in 4-10% of patients with ACKD. Two patients on CAPD for more than 6
      years without prior hemodialysis treatment developed renal malignancy in the
      setting of ACKD. Flank and abdominal pain was the presenting symptom in both
      patients neither of whom had hematuria. Renal ultrasound detected cystic lesions
      consistent with ACKD; malignant masses were ultimately identified by CT scan.
      Both patients underwent flank radical nephrectomy, resumed CAPD early in the
      postoperative period and continue on CAPD 9 and 4 months after surgery. One
      patient has since developed hepatic metastasis. ACKD is an important risk factor
      for the development of renal cell carcinoma not only in maintenance hemodialysis
      patients but also in the CAPD population. A high index of suspicion and serial
      ultrasound screening for ACKD is warranted in patients with long-term dialysis
      dependence.

PMID- 1361773
TI  - Safety of intraperitoneal calcium therapy in a rodent model.
AB  - Hypocalcemia can be a significant problem for the patient with end stage renal
      disease (ESRD). Although oral calcium supplementation and activated vitamin D
      therapy may be successful in normalizing serum calcium levels, occasional
      peritoneal dialysis patients have persistent and clinically significant
      hypocalcemia. Several researchers have successfully utilized intraperitoneal
      calcium therapy (ICT) for the treatment of this abnormality. In order to evaluate
      whether high calcium dialysate is well tolerated, we developed a model system of
      ICT in Sprague Dawley rats. These rats received intraperitoneal infusion with
      either normal or high calcium peritoneal dialysate. Studies in this experimental
      rodent model showed no evidence of adverse effects of high calcium dialysate when
      used for up to 71 days, except for unexplained weight loss in the high calcium
      group. ICT can be an important adjunct in the treatment of hypocalcemia seen in
      patients on peritoneal dialysis. This preliminary animal study supports its
      clinical use. However further long term studies in animal models will be
      necessary to establish the long term safety of this therapy.

PMID- 1361774
TI  - Hearing thresholds in CAPD patients.
AB  - Ultra high frequency (UHF, 10-20 kHz) and conventional audiometric thresholds
      (0,25-8 kHz) were obtained from 42 stable CAPD patients. Twenty-one (50%) and 11
      (25%) of the patients had UHF and conventional hearing loss respectively, when
      compared to age related control data. This was unrelated to length of chronic
      renal failure and number of treatments with ototoxic drugs. Sixteen of these
      patients were monitored audiometrically using UHF during a course of vancomycin
      therapy for peritonitis. There was no significant change in hearing thresholds.
      In conclusion there is high incidence of hearing loss in CAPD patients which is
      unrelated to ototoxic drugs.

PMID- 1361775
TI  - Effects of amino acid dialysate on appetite in CAPD patients.
AB  - The use of amino acid (AA) dialysate in CAPD patients may have theoretical
      disadvantages, since protein ingestion is known to suppress food intake in humans
      disproportionately to its energy value. Therefore we measured subjective appetite
      and food intake of CAPD patients in a cross-over study of 16 subjects (age 22-75
      years, BMI 19-31, > 3 months on CAPD, non-diabetic and not protein malnourished).
      They received, in random order, either 4 weeks of dextrose only (their usual
      treatment), or one AA (1%) exchange replacing the first dextrose exchange each
      day. Subjective measurements of food intake (3 day food record) and quantitative
      measurements of lunch time food intake were obtained during a morning dextrose
      exchange after 28 days of each regimen. Except for a reduction in feelings of
      fullness during the AA treatment, there were no effects on feelings of
      hunger/satiety, food appeal, lunch-time food intake, or on 3-day food intake. We
      conclude that the use of a daily AA (1%) dialysate for 4 weeks does not affect
      subjective appetite or food intake of CAPD patients. There may even be a
      beneficial effect as the feeling of fullness decreased with the AA treatment.

PMID- 1361776
TI  - Improved nutritional follow-up of peritoneal dialysis patients with bioelectrical
      impedance.
AB  - A threat to survival in renal failure, malnutrition in continuous ambulatory
      peritoneal dialysis patients (CAPD) is often occult as CAPD patients often gain
      weight masking actual protein malnutrition. Bioelectrical impedance (BEI)
      accurately assesses body composition in CAPD patients and uncovers subtle changes
      in lean body mass (LBM) that escape indirect anthropometric detection.
      Segregating parameters of body composition is crucial to nutritional management
      of CAPD patients in whom fat may account for overall weight gain. While both skin
      fold methods and BEI correctly distinguished thin and overweight patients in
      terms of fat mass, only BEI accurately segregated these patients by LBM (P =
      0.007). Serial weights of 39 CAPD patients followed longitudinally for three or
      more months did not correlate with BEI-measured changes in LBM. LBM was lost in
      49% of patients as determined by BEI, while serial weights detected a loss of LBM
      in 36% of these patients. Strikingly, by serial weights, 64% of patients
      demonstrated weight gain; however, in 24% of these an actual loss of LBM was
      demonstrated by BEI. BEI provides specific quantitation of LBM in CAPD patients
      with changing body habitus and unrecognized nutritional derangement.

PMID- 1361777
TI  - Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-I (PAI-I)
      levels in plasma and peritoneal effluent in patients on CAPD.
AB  - The formation of fibrin on peritoneal surface has been related to the appearance
      of adhesions both, in surgical and CAPD patients. It is known that mesothelial
      cells have fibrinolytic activity related with t-PA production. We studied plasma
      and overnight peritoneal effluent (OPE) from 20 CAPD stable patients. Antigenic
      PAI and t-PA were determined. These values and its correspondent peritoneal
      saturation indexes were compared to urea and creatinine MTCs, peritonitis
      incidence, UF capacity, protein losses, Pi, Ca, Na, CO2t, urea and creatinine OPE
      levels. Plasma t-PA 6.64 +/- 4.68 (2.4-20); Plasma PAI-I 24.8 +/- 17.1 (p < 0.001
      in respect to controls) (4-62); OPEt-PA 1.46 +/- 0.95 (0.4-4.6); OPE PAI-I 7.3 +/
      5.6 (0-20.4). Peritoneal saturation ratios were for t-PA 29.6 +/- 21% (6-65) and
      for PAI-I 34 +/- 32% (7-132). In conclusion our data do not support strong
      relationship between peritoneal t-PA/PAI system and the functional
      characteristics of the peritoneal membrane although plasma PAI-I, after an
      increase in patients at early stages on CAPD, shows a tendency to decrease over
      time and frequent peritonitis. The values of peritoneal saturation ratios for t
      PA/PAI are higher than expected for their molecular weight, which suggests local
      production. An elevated plasma t-PA levels has been found in older patients.

PMID- 1361778
TI  - Key factors to improve survival of elderly patients on CAPD.
AB  - The adequacy of dialysis is a primary concern when caring for patients undergoing
      CAPD. It is also important to analyze the key factors, which will reflect on the
      prognosis of elderly patients on CAPD. In this study, 60 CAPD patients were
      examined. The peritoneal and residual renal clearance of these patients were
      calculated every six months. These patients were divided into three groups (G-1 =
      poor, G-2 = fairly good, G-3 = good) according to their clinical parameter scores
      using a s-albumin,Ht,LBW, and s-cholesterol level. This study showed that the
      values of (KT/V) urea and Curea showed no statistical differences. These results
      therefore indicate that the major reason for the poor outcome in elderly patients
      is due to low dietary protein intake.

PMID- 1361779
TI  - Increased total body fat during PD treatment.
AB  - Sufficient nutritional intake is important to adjust the increased catabolic rate
      in uremic patients during dialysis treatment. Increased glucose absorption during
      PD treatment may, however, interfere with the amount of muscle- and fat-mass in
      the body. We have therefore studied the amount of total body fat composition in 8
      male PD patients (treatment period 79 months, range 3-23 before and 165.5 months,
      range 8-35.5 after the study). Food intake was recorded for 7 days twice in four
      patients with an interval of 6-8 months. Total body fat (%) was measured by means
      of a computerized model of near infrared interactance (IRI) ("FUTREX") on the
      dominant upper arm. The energy and protein intake were 1731 +/- 292 kcal. and
      86.9 +/- 17.2 g (n = 4) during the first recording period of food intake. In the
      second period the energy and protein intake were 1676 +/- 105 kcal and 72.7 +/-
      10.2 g (n = 4) (NS). The total body fat increased from 19.8 +/- 2.9 to 22.5 +/-
      3.0 (p < 0.05), in spite of unchanged total body weight. CONCLUSION: PD patients
      seem to accumulate fat during PD treatment with glucose as osmotic agent. This
      may influence the cardiovascular risks. The results indicate nutritional
      adjustments and possibly also increased physical activity.

PMID- 1361780
TI  - Peritoneal function tests: usefulness of simplified methods.
AB  - The Peritoneal Equilibration Test (PET) as standardized by Twardowski (T) and
      simplified Mass Transfer Coefficients (MTC) as per Garred (G) and Krediet (K)
      have been employed in our patients to assess: 1) the reproducibility of results,
      2) correlation between methods, and 3) usefulness of patient categorization by
      simplified methods in contrast to PET patterns. We have performed 29 standardized
      PET (Dianeal 2.5%) in 24 stable CAPD patients. We have collected dialysate
      samples at 0, 30, 60, 120, 180 and 240 minutes. With this data we were able to
      calculate the dialysate/plasma ratio for PET, MTC as per Garred and MTC as per
      Krediet. Our results were not significantly different from data reported by the
      original authors, except for PET D/P urea at 240': 0.91 +/- 0.07(T) vs. 0.87 +/-
      0.08 (our), p < 0.05. In our patients, good correlation was found between PET and
      MTC for urea, creatinine, and glucose, using both formulae (G and K). Patient
      categorization as High, High Average, Low Average, and Low by MTCs can well
      predict PET categorization with acceptable sensitivity and good specificity. We
      conclude there is good reproducibility of the methods. There is also a close
      correlation between PET, K and G methods for solute transport evaluation and
      patient categorization. Simplified methods can be substituted for the more
      complex ones.

PMID- 1361781
TI  - Pharmacokinetics of ciprofloxacin after intraperitoneal administration in
      uninfected patients undergoing CCPD.
AB  - Ciprofloxacin is increasingly used to treat peritoneal dialysis related
      peritonitis. We studied the pharmacokinetics of intraperitoneally administered
      ciprofloxacin in six uninfected CCPD patients. In a randomized cross-over setting
      ciprofloxacin was added either to a long dwell exchange (lastbag) or to four
      short dwell exchanges (dwell time 1.5 h). Addition of ciprofloxacin (25 mg/l)
      during the four short dwell exchanges resulted in dialysate levels of 21.1-13.3
      mg/l during these exchanges. In the subsequent last bag devoid of ciprofloxacin a
      dialysate Cmax,D of 1.38 mg/l was observed at 30 min. Mean +/- SD serum Cmax,S
      was 0.59 +/- 0.29 mg/l after 5.4 h. Instillation of 100 mg/l ciprofloxacin in the
      last-bag yielded Cmax,D of 99.1 mg/l, falling with a t1/2 of 3.3 h towards levels
      < 2 mg/l at 19.8 h. A mean +/- SD serum Cmax,S of 0.69 +/- 0.19 was reached after
      4 h. During four subsequent 1.5h exchanges without ciprofloxacin dialysate levels
      were < 0.1 mg/l. Instillation of 25 mg/l ciprofloxacin in the last-bag yielded a
      Cmax,D of 21.7 mg/l, falling towards levels < 2 mg/l at 15 h with a t1/2 of 3.85
      h. A mean +/- SD serum Cmax,S of 0.26 +/- 0.03 was reached after 8 h. We conclude
      that the rapid absorption of ciprofloxacin from the dialysate into the tissues
      requires ciprofloxacin to be administered to all CCPD bags to ensure bactericidal
      dialysate levels. When therapeutic serum levels are required higher
      intraperitoneal doses or an oral or i.v. loading dose is warranted.

PMID- 1361782
TI  - Evaluation of CNS-function in CAPD patients using magnetoencephalography (MEG):
      comparison with hemodialysis patients.
AB  - In order to evaluate the CNS-function of uremic patients, the magnetic activity
      emitted from the brain of 20 pts (10 pts on CAPD and 10 on HD) was measured. MEG
      consisted of taking 32 consecutive records from the 32 equally spaced points
      chosen on the skull in uremic pts around our reference points T3, T4, P4, F3, F4
      of the international 10-20 electrode placement point system. MEG data were
      converted using an AD-converter with sampling frequency 256 Hz and stored in a
      P/C. Our results showed significant differences between the two groups. In all HD
      pts there was abnormal magnetic brain activity with high spectral amplitudes (in
      the band 2-7 Hz) which was more prominent in pts in hemo for more than 4 years.
      The magnetic activity was within normal ranges in all CAPD pts. We conclude that:
      1) There is high magnetic brain activity in HD pts, which in accordance with the
      EEG findings are signs of diffuse encephalopathy. 2) CAPD pts show a very low
      magnetic brain activity which must be interpreted as normal brain function, and
      3) MEG can be useful in further measurement of adequacy of dialysis.

PMID- 1361783
TI  - CAPD in end stage patients with renal disease due to diabetes mellitus--an
      update.
AB  - Large numbers of diabetics with renal failure have been treated by continuous
      ambulatory peritoneal dialysis (CAPD). Overall 1-year patient survival varies
      from 51% to 87%. Mortality is due to cardiovascular disease in more than 50% of
      the cases. Young diabetics with good blood pressure control and without cardiac
      disease have a chance at long survival on CAPD. In comparison to hemodialysis,
      CAPD yields better patient survival for young diabetics and worse for old
      diabetics, worse technique survival, probably greater overall morbidity, and
      similar rates of progression of retinopathy, neuropathy and peripheral vascular
      disease. Adequacy of peritoneal clearance and peritoneal ultrafiltration
      characteristics are similar between diabetics and non-diabetics on CAPD. CAPD is
      associated with better preservation of renal function than hemodialysis in
      diabetics. The rates of CAPD peritonitis do not differ substantially between
      diabetics and non-diabetics. However, diabetes appears to be associated with
      higher incidence of tunnel infection. Hyperlipidemia is generally less severe in
      diabetics than non-diabetics on CAPD, but malnutrition is more frequent in
      diabetics. CAPD has many attractive features and several drawbacks for the
      management of diabetics with end stage renal failure (ESRF). Its ultimate success
      will depend on the outcome of efforts to improve cardiovascular mortality,
      malnutrition, hyperlipidemia and catheter-related infections.

PMID- 1361784
TI  - Multiple use of cycler set in cycler peritoneal dialysis.
AB  - STUDY OBJECTIVE: To evaluate the multiple use of cycler set with universal
      connector set. DESIGN: The study was designed to reuse the cycler set for two to
      three treatments, each of 16-24 hours using Pac-X or Pac-Xtra cycler and to
      continue to use the same set if the patient was disconnected for any reason.
      SETTING: Tertiary-referral university hospital. PATIENTS AND METHODS: 204 ESRD
      patients on peritoneal dialysis (PD) admitted to University Hospital from January
      1989 to July 1991 were studied. The patients were disconnected and reconnected in
      between or during PD treatments. Five-liter dialysate bags were used. All the
      fluid was either set initially or added as clinically indicated. RESULTS: 2491
      cycler PD treatments were performed with Pac-X and Pac-Xtra cyclers using 940
      cycler tubing sets. 1624 disconnections were made in between and 336 were made
      for radiological investigations, special procedure, physical therapy and surgery
      during PD treatments. No episode of peritonitis or mechanical failure occurred.
      The multiple use resulted in 62% reduction in cycler sets thereby reducing the
      disposable supplies and a substantial saving in the nursing time. CONCLUSIONS:
      The multiple use of cycler set with universal connector and manifold set was safe
      and economical in the patients undergoing cycler PD in the hospital setting.

PMID- 1361786
TI  - Peritoneal dialysis training in a patient with multiple congenital anomalies.
AB  - We report an adult patient with multiple congenital anomalies including absent
      right arm, short stature, and scoliosis who has been trained and successfully
      performs continuous cycling peritoneal dialysis independently. Motivated patients
      with end stage renal disease and various anomalies should be considered for
      peritoneal dialysis training.

PMID- 1361785
TI  - A comparison of sleep-disordered respiration in ESRD patients receiving
      hemodialysis and peritoneal dialysis.
AB  - STUDY OBJECTIVE: To compare sleep-disordered respiration in ESRD patients
      receiving peritoneal dialysis and hemodialysis. DESIGN: Subjective and objective
      measures of sleep were recorded in two groups of ESRD patients receiving PD and
      HD. SETTING: Tertiary-referral university hospital PATIENTS AND METHODS: Fifteen
      PD patients (12 males, 3 females) and 15 HD patients (11 males, 4 females) were
      studied for two nights in the sleep laboratory. RESULTS: Ten of the 15 PD
      patients and 8 of the 15 HD patients reported multiple types of sleep
      difficulties (NS). In the PD group, seven described substantial difficulty
      initially going to sleep; ten were troubled by awakenings during the night, while
      seven suffered from daytime sleepiness. In the HD group, seven described
      substantial difficulty initially going to sleep; eight were troubled by
      awakenings during the night, while five experienced day-time sleepiness. No
      significant difference was observed in total sleep time, intermittent wake time,
      sleep latency, sleep efficiency, total disordered breathing events, minimum
      oxygen saturation and periodic leg movements between the PD and HD groups. Sleep
      apnea was noted in 9 of 15 PD and 8 of 15 HD patients. CONCLUSIONS: This study
      indicates that the incidence and severity of sleep apnea is similar in ESRD
      patients receiving chronic peritoneal dialysis and hemodialysis.

PMID- 1361787
TI  - Archaeology and the "thrifty" non insulin dependent diabetes mellitus (NIDDM)
      genotype.
AB  - In recent decades, non-insulin dependent diabetes mellitus (NIDDM) has become a
      major public health problem in several parts of the world. A complex disorder,
      NIDDM is associated with an increased risk of blindness, coronary heart disease,
      peripheral vascular disease, and kidney failure (1). The epidemiology of NIDDM is
      providing new insights into many aspects of this disease, including prevalence,
      incidence, morbidity, and mortality (2). My objective is to explain the high
      prevalence of a NIDDM susceptible genotype(s) in several distinct populations:
      American Indians, Australian Aborigines, and Pacific Islanders. The susceptible
      genotype may have been selected into these populations because of unusually
      frequent food shortages that occurred during the initial colonization of 'new
      worlds'. NIDDM has been shown to have a strong genetic component (3) that may
      include a 'thrifty' genotype(s) (4,5). The 'thrifty' genotype(s) may have once
      allowed founding populations to survive feast' and 'famine' conditions for
      several generations. With an assured food supply and a sedentary lifestyle,
      however, the 'thrifty' genotype(s) becomes disadvantageous, leading to obesity,
      increased insulin resistance, beta cell decompensation, and NIDDM (3,6).

PMID- 1361788
TI  - Adequacy of dialysis in CAPD and cycler PD; the PET is enough.
AB  - Assessment of adequacy of dialysis has become a necessary part of all peritoneal
      dialysis programs; this task is particularly burdensome in home cycler patients.
      To test the hypothesis that the Peritoneal Equilibration Test (PET) reliably
      predicts clearance, as measured by classical clearance methodology, both CAPD and
      cycler patients underwent PET tests and clearance studies. In cycler patients,
      Dialysis to Plasma Ratios (D/P) for urea nitrogen (UN) and D/P for creatinine as
      determined by clearance methods correlated extremely well with those obtained by
      PET test. D/P creatinine also correlated well (clearance versus PET) in CAPD
      patients; D/P UN approached unity in all CAPD patients with dwell times of 4
      hours or longer. In all cases, the PET prescription was highly accurate in
      predicting 24-hour clearance results. These results are useful in those patients
      in whom 24-hour home collections are inconvenient or impossible, especially in
      cycler patients.

PMID- 1361790
TI  - Effect of glucose concentration and dwell time of dialysis fluid on the
      antibacterial defense in the peritoneal cavity of rats.
AB  - To study the influence of dialysis fluid on the antibacterial defense in the
      peritoneal cavity of rats, especially glucose concentration and dwell time, an
      experimental infection was developed. Rats were injected intraperitoneally with
      dialysis fluid with a glucose concentration of 1.36%, 2.27%, or 3.86% or
      physiological saline. Subsequently 1, 4 or 18 hr thereafter an inoculum of
      approximately 3 x 10(8) colony forming units of Staphylococcus aureus was
      administered intraperitoneally (i.p.) Next, 24 hr after the inoculation the
      number of viable bacteria was determined. Peritoneal cells (PC) isolated 1, 4 and
      18 hr after the administration of dialysis fluid were tested for their capacity
      to kill S. aureus in vitro. A positive relation was observed between the glucose
      concentration and the number of bacteria isolated; the longer the dwell time the
      lower this number. In vitro PC isolated at the various intervals did not differ
      in their capacity to kill S. aureus. It is concluded that the glucose
      concentration in dialysis fluid impairs the antistaphylococcal defense in the
      peritoneal cavity of rats. A relatively long dwell time enhances this defense.
      These results cannot be explained by a lower capacity of the PC to kill S. aureus
      in vitro.

PMID- 1361789
TI  - Adherence of Staphylococci to plastic, mesothelial cells and mesothelial
      extracellular matrix.
AB  - In this study we have investigated whether mesothelial cells (MC) and mesothelial
      extracellular matrix (ECM) are suitable substrates for the adherence of
      Staphylococci. Mesothelial cells were isolated from the peritoneal dialysis
      effluent by making use of their lack of Fc-receptors and capacity to attach
      firmly to plastic. After 10 days post-confluency the MC monolayer was removed
      with 0.1% Triton-X100 and the presence of an ECM shown by enzyme linked
      immunosorbent assay (ELISA). The ELISA showed the presence of fibronectin and
      laminin but not of type IV collagen and vitronectin. Bacterial adherence assays
      with Staphylococcus aureus (N:3 isolates) adhered well to both ECM (33.4%) and MC
      monolayers (40.2%; ECM vs. MC monolayers p < 0.03). Staphylococcus aureus adhered
      significantly better to both ECM (p < 0.05) and MC monolayers (p < 0.05) when
      compared to plastic. Staphylococcus epidermidis (N:3 isolates) showed similar
      adherence for plastic (22.1%) and MC monolayers (23.5%); mesothelial ECM was a
      relatively poor substrate for adherence (6.8%, p < 0.03). In conclusion, results
      obtained sofar do not indicate an increased risk for adherence of Staphylococci
      when the mesothelial ECM is exposed.

PMID- 1361792
TI  - Significant reduction of peritonitis rate by the use of Twin-bag system in a
      Canadian regional CAPD program.
AB  - In a regional CAPD program in Northern Alberta, Canada, the peritonitis rates
      among patients undergoing CAPD treatment were quite high: 1/8.3 and 1/7.4 per
      patient month from a population of 75 and 76 patients in 1989 and 1990
      respectively. Our patient population is comprised of different ethnic groups,
      separated widely from the dialysis centre; over half of them are above the age of
      60 years. As it is not possible to change the patient characteristics in our
      centre, we switched to the Twin-bag disconnect system in 83 out of a total of 103
      patients in 1991. With this change our overall peritonitis rate has significantly
      improved to 1/14 per patient months and 1/17 per patient months in patients using
      the Twin-bag system. This improvement in the peritonitis rate has occurred
      without any change in our patient characteristics. We find the improvement in our
      peritonitis rate is due to the use of the new Twin-bag system, which provides
      total disconnection with no spikes and thereby reduces peritonitis due to touch
      contamination.

PMID- 1361791
TI  - Intraperitoneal pressure, peritoneal permeability and volume of ultrafiltration
      in CAPD.
AB  - Peritoneal permeability (PP), hydrostatic intraperitoneal pressure (IPP) and the
      overall volume of ultrafiltration (UF) were measured in 23 patients treated by
      CAPD under stable conditions. PP, IPP and UF were measured during the same
      exchange with a 2-liter bag with 3.86% glucose, dwell time of 2 hours. PP was
      evaluated with 3 indices: glucose peritoneal desaturation at 2 hours, urea
      peritoneal saturation at 2 hours, and crossing time of glucose and urea
      peritoneal equilibration curves. IPP was evaluated at inspiration (IPPinsp) and
      at expiration (IPPexp)-giving IPPmean-by measuring the height of the dialysis
      fluid in the PD line under atmospheric pressure, with point zero located on the
      axillary line of the subject in strict supine position. Net UF volume was
      inversely correlated with IPPmean. The net UF volume was strongly affected by IPP
      since a 1 cmH2O increase in IPPmean caused a decrease of 74 ml in global UF in 2
      hours, probably by modification of the lymphatic reabsorption and perhaps of the
      transcapillary UF.

PMID- 1361793
TI  - Relationship between peritonitis and exit site infections in CAPD.
AB  - This study was designed to retrospectively review the experience in this center
      with oral ciprofloxacin 500 mg bid and ip vancomycin 25 mg/L in the treatment of
      CAPD-related exit site infections and to determine the relationship between exit
      site infections and peritonitis. There were 48 patients with 172 episodes of
      infection (23 had both infections, 22 had peritonitis only, 3 had exit site
      infections only). Thus, exit site infections occur infrequently in the absence of
      peritonitis (23% of occasions). Of the 35 patients who had peritonitis as the
      first infection, 13 (37%) subsequently developed an exit site infection. The mean
      +/- SD period from an initial peritonitis to a subsequent exit site infection in
      these patients was 8.2 +/- 8.0 (range 1-28) months. Of the 22 patients with 34
      exit site infections, there were 15 (44%) treatment failures, of which 10 (67%)
      were relapses or possible relapses. S. aureus was the most common isolate. 5% of
      exit site infections were culture negative. Follow-up was incomplete for many
      patients resulting in many instances of no further cultures, and compliance could
      not be assured. This combination was associated with a high incidence of
      treatment failures in this setting.

PMID- 1361794
TI  - Erythema: does it indicate infection in a peritoneal catheter exit site?
AB  - The definition of a peritoneal catheter exit site infection varies from one
      dialysis center to another. A review of abnormal appearing exit sites (n = 334 in
      169 patients) from 1/83 to 3/91 was done to compare outcome in exit sites
      presenting with erythema (39, 12%) to those with drainage plus erythema (72, 22%)
      or drainage alone (223, 67%). Resolution of the abnormality occurred in 48% of
      those exit sites with drainage, 62% with erythema and drainage, and 79% with
      erythema alone (p < 0.005). S. aureus was present in 62% of the cultured exit
      sites which had erythema alone, 64% with erythema plus drainage, and 41% with
      drainage alone, while Gram negative rods were present in 13%, 12%, and 35%,
      respectively (p < 0.005). Twenty-three of the 39 exit sites with erythema were
      not initially treated with antibiotics; 87% resolved compared with 69% of those
      treated immediately with antibiotics (p = ns). Seven of the 8 erythematous exit
      sites that did not resolve progressed to tunnel infection and/or peritonitis and
      required catheter removal, despite the addition of antibiotics in the three
      initially untreated. Six of the 8 unresolved erythematous exit sites were due to
      S. aureus. These results indicate that, although drainage is the commonest exit
      site abnormality and has the worst prognosis, peri-catheter erythema is not
      always benign, representing an early sign of infection in some cases.

PMID- 1361795
TI  - Imipenem versus netilmicin and vancomycin in the treatment of CAPD peritonitis.
AB  - Imipenem/cilastatin is a new thienamycin antibiotic with a broad bactericidal
      spectrum. We undertook a prospective randomised study to compare the safety and
      efficacy of intraperitoneal (IP) imipenem/cilastatin (2 gm daily) [group A; 21
      patients, mean age 49.2 years] with a combination of IP netilmicin and vancomycin
      (500 and 60-100 mg daily resp.) [group B; 20 patients, mean age 55.2 years] in
      CAPD peritonitis. Each patient underwent 4 daily CAPD exchanges with antibiotics
      in alternate exchanges. The causative organisms were similar in both the groups
      as was the duration of therapy (gr.A: 6.8 +/- 0.27 days; gr.B: 7.2 +/- 0.51 days;
      p = NS). Complete cure was marginally better with imipenem/cilastatin (gr.A;
      94.1%, gr.B: 83.3%) with less relapses (gr.A: 1 episode; gr.B: 3 episodes). One
      episode in gr.A (S. aureus) and 2 in gr.B (Yeast & Proteus) failed to resolve and
      required catheter removal. Two gr. A patients developed generalised convulsions
      which settled after discontinuation of the drug. Whilst the results show no
      significant difference in the outcome in the two groups, the use of IP imipenem
      would offer a possible advantage as a single antibiotic. Larger experience is
      needed before imipenem can be recommended as a 'blind' first line agent for CAPD
      peritonitis.

PMID- 1361796
TI  - Treatment of CAPD peritonitis with clavulanate potentiated ticarcillin.
AB  - A total of 16 episodes of peritonitis in 14 patients (9 males, 5 females), were
      treated with Clavulanate potentiated ticarcillin (TC), a -lactamase stable
      parenteral penicillin. All the pts were hospitalized and received initial loading
      dose of 3.2 gr intraperitoneally (i.p.) in a 6-hour 1 L exchange, which was
      followed by four 1 L exchanges with 320 mg/LTC. The therapy was continued for ten
      days. The bacteria isolated were: Staph. epid. (4), Staph. aureus (2), Strept.
      viridans (1), Enterococcus (1), Klebsiella Pneum. (1), Serratia (1), Enterobacter
      (1), Pseudomonas species: stutszeri (2), cepacia (1), fluorescens (1), negative
      cultures (1). Recurrence of peritonitis was seen in three patients with
      Pseudomonas (stutszeri (2), fluorescens (1)) peritonitis, 10-16 days after
      cessation of therapy. No clinical or biological side effects were seen in any
      patient during and/or after the therapy. These results suggest that, i.p.
      monotherapy of TC is effective in the treatment of CAPD peritonitis, while in
      cases of Pseudomonas peritonitis more specific regimens should be used.

PMID- 1361797
TI  - Treatment of Staphylococcus aureus nasal carriers in CAPD with mupirocin.
AB  - We have studied the efficacy of topical Mupirocin for elimination of
      Staphylococcus aureus (Staph. aureus) nasal carriage in CAPD patients. Staph.
      aureus nasal carriers in our CAPD program were randomized to one of two groups:
      Group 1, treated with Mupirocin, and Group 2, treated with neomycin sulphate
      nasal ointment. The prevalence of Staph. aureus nasal colonization was 44% for
      patients (24/54) and 17% for dialysis partners (5/29). Group 1 included 11
      patients and 1 partner, and Group 2, 8 patients and 2 partners. In Group 1, the
      eradication rate was 100%, and the recolonization rate was 0, 8, 41, 55 and 66%
      at 1, 2, 3, 6 and 10 months. In Group 2, the eradication rate was 40%, with a
      recolonization rate of 0.25 and 75% at 1, 2 and 3 months. Re-treatment with
      mupirocin was successful in 66% of the cases, compared to 20% for neomycin. The
      MIC90 of mupirocin for Staph. aureus was 0.5 mcg/mL, with an increase to 4 mcg/mL
      towards the end of the study. During the study period, there was a very low
      incidence of Staph. aureus peritonitis or catheter-related infections in patients
      treated with mupirocin. Secondary effects of mupirocin were negligible. Mupirocin
      is more effective than neomycin sulphate for the elimination of Staph. aureus
      nasal colonization in patients undergoing CAPD. Periodic re-treatment is
      frequently necessary, given the significant recolonization rate.

PMID- 1361798
TI  - The modulation by fresh and spent peritoneal dialysis fluids of antibiotic
      kinetics directed against Staphylococcus epidermidis biofilms.
AB  - The presence of CAPD peritoneal catheters has an association with S. epidermidis
      infections which are relatively resistant to antibiotic therapy. This resistance
      has been ascribed to the formation by the bacteria of a protective matrix on the
      catheter surface enclosing the bacteria to form a bacterial biofilm. The rate of
      action of 14 antibiotics on standardized S. epidermidis bacterial biofilms over a
      5 day exposure period and the modifying effects of fresh and spent peritoneal
      dialysis fluids were assayed. There were significant differences in the rates of
      antibiotic action. Fresh dialysis solution markedly augmented rifampin activity,
      and to a lesser extent, vancomycin, cloxacillin and teicoplanin but antagonized
      ciprofloxacin. Spent dialysis fluid generally augmented the activity of
      antibiotics, notably cloxacillin and cephalothin. Rifampin was bactericidal in
      both fresh and spent dialysis fluids. Fusidic acid was a poor performer in all
      tests.

PMID- 1361799
TI  - Peritonitis and the patient with human immunodeficiency virus (HIV).
AB  - The prevalence of HIV positive patients (HIV pts) with ESRD is likely to increase
      and many will be going on CAPD. There are, however, factors which cause one to be
      concerned about a possible increased risk of peritonitis in these patients. These
      include not only their impaired immune and nutritional status, but often their
      mental status. We examined the incidence and type of peritonitis among the 184
      patients who have been in our program since December 1983 for a total of 4,017
      patient months (pt mo). During this time we treated 9 known HIV pts (4 drug users
      and 5 homosexuals) for a total of 114 pt mos. We also looked at albumin,
      cholesterol, and creatinine as possible risk markers. We found a greater than two
      fold incidence of peritonitis in the HIV positive patients and that low albumin
      was a significant risk factor in the HIV negative patients, but not in the HIV
      positive patients.

PMID- 1361800
TI  - Staphylococcus aureus nasal carrier status (SANCS) in CAPD patients; is it
      induced or favored by subcutaneous rHu-erythropoietin?
AB  - Staphylococcus aureus nasal carriage status (SANCS) has been recognized as a risk
      factor for patients on CAPD, due to a higher probability of suffering peritoneal
      catheter infections. The use of subcutaneous drugs (insulin dependent diabetics,
      drug addicts, HD patients and antiallergic vaccines), has been associated with
      increased risk of SANCS. On CAPD, erythropoietin (EPO) is almost universally used
      by the subcutaneous route. The objective of this paper was to evaluate the
      incidence and prevalence of SANCS in 85 CAPD patients by means of nasal smear and
      the influence of SANCS on peritoneal and catheter infection rate. Patients were
      divided in four groups according to diabetic status and EPO treatment (mean dose
      2000 u. twice a week). The prevalence of SANCS in control groups was 30% in non
      diabetics and 23% in diabetics. EPO treated patients showed a prevalence of SANCS
      of 39% in non-diabetics and 45% in diabetics due to the presence of 7 and 5
      carrier patients respectively. SANCS patients (29% of the population), suffered
      45% of peritonitis and 42% of exit-site infections caused by S. aureus. In a
      prospective part of the study, there was no difference in the frequency of
      developing positive cultures among EPO and control (30% of patients). No male EPO
      treated patients developed SANCS. We conclude that it is necessary to monitor S.
      aureus nasal carrier status periodically in CAPD patients especially in women.
      Whether or not subcutaneous erythropoietin treatment is implicated
      pathogenetically with SANCS, is not clarified by our data because of the frequent
      spontaneous appearance of SANCS among CAPD patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1361801
TI  - Detection of CMV-DNA in cells from peritoneal fluid of IPD/CAPD patients by
      polymerase chain reaction.
AB  - Documented viral peritonitis in peritoneal dialysis patients is rare, although up
      to 20% of all cases are culture negative (non-fungal, non-bacterial). CMV
      infected peritoneal cells may serve as a reservoir for reinfection and/or
      reactivation of CMV after renal transplantation. CMV-Polymerase Chain Reaction
      (CMV-PCR) amplification analysis identified CMV-DNA in cells from the peritoneal
      dialysate of 8 patients (3 culture negative peritonitis from a total of 5
      examined) and 5 asymptomatics) out of 17 potential kidney transplant recipients
      (6 on IPD 16.6 +/- 6 months, range 10-29 months; 11 on CAPD 28.1 +/- 25 months,
      range 2-81 months). Serum titers (10/17 patients analyzed) of anti-CMV IgG
      antibodies ranged from < 1:20 to 1:320 (no correlation with CMV-DNA) while anti
      CMV IgM antibodies were undetectable. Detection of CMV specific sequences in
      peritoneal cells in peritoneal dialysis patients by the PCR assay is sensitive
      (amplification of a 133 bp immediate early CMV gene sequence allows detection of
      10 CMV infected cells in a background of 10(5) uninfected peritoneal cells),
      rapid (1 day visual, 3 days with confirmation by Southern hybridization),
      specific (no amplification of human embryo and kidney cell DNA, or HSV, EBV, or
      VZV infected cells) and is non-invasive in IPD/CAPD patients since no additional
      invasive technique is required.

PMID- 1361802
TI  - Peritoneal clearances of carbon dioxide in the rat.
AB  - In our previous rat studies (Kidney Int. 1991; 39: 608-617) we evaluated
      peritoneal clearances (Cp) representing near exclusively diffusive CO2 transfer:
      for isosmotic (0.37% dextrose) and hyperosmotic (15% dextrose) solutions with pH
      7.2-7.3, CpCO2 were 1.20 +/- 0.08 and 1.84 +/- 0.04 ml/min, respectively. In the
      present studies we have compared Cp of CO2 gas and HCO3- in anesthetized rats (n
      = 22) using solutions with dextrose contents as mentioned above but with pH 6.5
      or 7.6; we have also evaluated how much Cp CO2 measurements obtained with
      solutions at these pH values differ from Cp shown earlier with the solutions of
      pH 7.2-7.3. Cp of CO2 gas and HCO3- were significantly higher under hyperosmotic
      than isosmotic conditions. The use of solutions of pH different from 7.2-7.3
      resulted in higher Cp of CO2 gas: with isosmotic solutions of pH 6.5 and 7.6 mean
      increases were 25 and 75%, respectively; with hyperosmotic solutions respective
      increases were 45 and 134%. We conclude that dialysis solution osmolality and pH
      significantly change Cp of CO2 gas and HCO3- in the rat. For evaluation of
      peritoneal blood flow from diffusive transfer parameters of CO2 gas, smaller
      overestimation can be expected when dialysis solution pH is slightly under-than
      overadjusted compared to blood pH.

PMID- 1361803
TI  - Does catheter immobilization reduce exit-site infections in CAPD patients?
AB  - This study was undertaken to ascertain the effectiveness of an immobilization
      device in reducing exit site infections (ESI) in CAPD patients, and whether
      immuno-suppressive therapy, diabetes, disconnect system and Staphylococcus aureus
      nasal carriage had any bearing on the incidence of ESI. Sixty-six patients having
      a Tenckhoff catheter placement were randomly allocated into one of three groups;
      immobilizer, tape and non-immobilized group. The groups were monitored for the
      incidence of ESI over a total period of 347 patient months. The results show no
      significant difference in infection rates between the three groups, nor do the
      factors mentioned have any bearing on ESI rate. Whilst immobilization is
      important, the ineffectiveness of this device was probably related to its design
      problem.

PMID- 1361804
TI  - The impact of peritonitis on CAPD results.
AB  - The impact of peritonitis on CAPD results was evaluated in 1990 pts (mean age +/-
      SD:58.4 +/- 14.8 yrs, 55.9% males), treated in 30 centres participating in
      Italian PD Study Group, during 1980-89, with an overall observation period of
      3953 years (mean +/- SD 24.1 +/- 22.3 months). The incidence of peritonitis
      decreases from 1.21 (1980-84) to 0.48 (1985-89) ep/year (overall:0.68) with a
      significant (P < 0.001) reduction of the probability of developing the first
      peritonitis episode (FPE) through the same periods. The probability of developing
      FPE and the relative risk of peritonitis were significantly lower (P < 0.001) in
      pts for whom CAPD has been the first treatment (80.1%); on the contrary these
      parameters did not gain significant difference according to sex, age 65 years,
      diabetes or cardiovascular disease. As far as the organisms responsible for
      peritonitis are concerned a significant reduction of S. epid. and an increase of
      S. aureus, other Gram pos. and Pseudomonas was observed in the second 5-yr
      periods. Peritonitis episodes caused catheter removal in 8.2% of cases and were
      associated with catheter infection in 10.8% of cases. Peritonitis accounted for
      24.2% of hospitalization causes and for 6.7% and 30.0% of death and of drop-out
      respectively. The probability of death and drop-out was significantly high (p <
      0.001) in pts with a peritonitis incidence > 1 ep/year than in those with < 0.5
      ep/year. The probability of drop-out due to peritonitis was not higher in
      diabetic or older patients.

PMID- 1361806
TI  - A new catheter to prevent exit-site infection in peritoneal dialysis.
AB  - In order to prevent exit-site infection, we studied a new Tenckhoff-derived
      catheter, named the "Malpighi catheter," capable of avoiding sinus tract
      formation. The outer cuff of this new device is 3.5 cm long and is deliberately
      positioned half-extruded; in fact, half of the cuff remains outside the skin exit
      site. The implantation technique is identical to that of the standard two-cuff
      Tenckhoff catheter. We implanted eight Malpighi catheters in 5 CAPD and 3 IPD
      patients. The observation period was 146 patient-months (range 14-23, M +/- SD
      18.2 +/- 3.3). We observed excellent adhesion between the outer cuff and
      surrounding tissue. Actually, by pulling the catheter the skin around the half
      extruded cuff becomes cone-shaped, with the cone's apex tightly stuck to cuff and
      the sinus tract disappearing completely. Only one case of exit-site infection by
      Staphylococcus aureus and two cases of ulcer of the skin beneath the external
      part of the half-extruded cuff were observed. These complications were resolved
      completely. No catheter needed to be removed and there were no leakages. The
      histological study of the cuff showed a good infiltration of the dacron cuff by
      fibrous tissue. On the grounds of our preliminary experience, we believe that the
      absence of the sinus tract, the formation of an efficient mechanical and
      bacterial barrier and the reduction of exit-site infection incidence are all
      factors that encourage further research.

PMID- 1361805
TI  - CAPD bag changing with integrated disconnect system gives lower incidence of
      peritonitis than with UV-box system.
AB  - The use of a UV-box disconnect system reduces the incidence of peritonitis as
      compared with manual exchanges. An integrated disconnect system (IDS) also gives
      good results. See Figure 1. From 1988-1991, we prospectively compared two groups
      of patients using either a UV-box disconnect system (Baxter, n = 18, mean age 64,
      range 28-75 yrs) or an IDS (Baxter, n = 25, mean age 53, range 30-78). The
      Tenckhoff catheter had been inserted by the same technique in all patients, and
      the training program and nursing care were also identical. Since many younger
      patients preferred IDS and refused randomization, age was significantly lower in
      the IDS group. All peritonitis episodes (PER) were registered. Excluded from
      calculations of PER were episodes most probably not due to failure in connective
      device: PER after incidental penetration of the dialysis bags, deep penetrating
      tunnel infections and in the direct course of abdominal surgery. RESULTS: There
      were significantly fewer months with PER (one month = 1 PER; Chi-2 = 6.45, p <
      0.05) in patients using the IDS (3 PER/269 months) compared with those using the
      UV-box system (15 PER/355 months). The IDS was requested mainly by younger
      patients, while some older patients found it to be too complicated. CONCLUSION:
      The integrated disconnect system is especially acceptable by younger patients,
      and patients using the IDS show a low incidence of peritonitis.

PMID- 1361807
TI  - Enhanced peritoneal dialysis delivery with PD-PLUS.
AB  - We prospectively studied the effects of enhanced continuous ambulatory peritoneal
      dialysis (CAPD) on the normalized protein catabolic rate (NPCR) and Kprt/V of two
      patients with zero residual renal function and marginal or below minimal HCFA
      values on urea kinetic modeling (Kprt/V = 0.21). Predictable increases in NPCR
      (from 0.61 to 0.76 and from 0.73 to 0.81 gm/kg/day, respectively) were seen after
      two weeks of enhanced CAPD achieved by the addition of a fifth nighttime exchange
      by a portable, easily operable, automated device (PD-PLUS).

PMID- 1361809
TI  - An assessment of the flow rate within peritoneal dialysis catheters, using a
      standardized in vitro technique.
AB  - A variety of peritoneal dialysis catheters are used in clinical practice. The
      catheters are mainly described by their design, French number (circumference in
      mm) and length. However, this description does not provide information about the
      catheters inflow and outflow rates. We have therefore, studied flow rates of 18
      adult catheters, using a uroflowmeter. Inflow rates were measured with the inflow
      bag 100 cm and 145 cm above the tip of the catheter, and outflow rates were
      measured with the flow transducer located 35 cm and 80 cm below the tip of the
      catheter, imitating situations where patients are sitting in a chair or laying in
      a bed during fluid exchanges. Ten measurements were made for each catheter at all
      heights. We found that catheter designs do affect flow rates. Straight catheters
      had statistic significantly faster inflow and outflow rates compared to curled
      catheters (p < 0.001). Moreover, curled catheters had statistic significantly
      faster flow rates than Swan Neck catheters (p < 0.001). The length and internal
      diameter of the catheter was found to be the determining factor for the
      differences in flow rates.

PMID- 1361808
TI  - Analysis of clinical experience with a new twist lock connectology.
AB  - The DextroLyte II (Dex II) Peritoneal Dialysis System was designed to improve
      safety and convenience in dialysis therapy. Connectors introduced with this
      system have a threaded recessed male connector with a corresponding female
      counterpart. Products are provided for CAPD, Single Use Y, Long Life Y and CCPD.
      Safety and convenience features intended to reduce peritonitis rates and improve
      patient acceptance include the following: 1. Connectors with threaded male and
      corresponding female counterparts which provide a dual seal 2. Easy-to-break
      frangible which seals the solution bag until ready for use 3. A flange on the
      connector ensures proper hand placement by providing a safety shield to prevent
      contamination during connection 4. A hinged shield containing an impregnated
      povidone-iodine sponge easily snaps around the bag connector 5. A Quick
      Disconnect Clamp (QDC) provides external occlusion permitting safe disconnection
      for bagless techniques without opening the system 6. A standard medication port
      provides easy access for administration of intraperitoneal medication Results of
      a multicenter study performed in nine centers are as follows: Total patient
      participants 121 Total patient months 1207 Overall peritonitis rate 1 episode in
      43 patient months We conclude that the Dex II peritoneal dialysis systems provide
      safe dialysis therapy as evidenced by the exceptional peritonitis rates. Patient
      acceptance has been excellent due to the inclusion of the safety and convenience
      features described.

PMID- 1361810
TI  - Subcutaneously implanted catheters reduce the incidence of peritonitis during
      CAPD by eliminating infection by periluminal route.
AB  - Recent experiences with Y-connectors suggest that the flush-before-fill
      effectively reduces intraluminal infection. Periluminal infection, however,
      remains an important route of peritonitis (P). We have recently reported reduced
      P incidence with the introduction of a new access technique as described by
      Moncrief in which the external segment of peritoneal catheter is left implanted
      subcutaneously for 6 weeks before exteriorization and bag exchanges. P developed
      once every 14.0 patient-mos with the new access while the incidence was one
      episode per 10.7 mos with conventional access. Significantly fewer patients with
      the new access compared to those with conventional access experienced P during
      the observation period (p < 0.01). Although the overall incidence of exit-site
      infection (ESI) was not different, there were significantly fewer episodes of
      simultaneous P and ESI with the new access (2P in 47 episodes of ESI) than with
      conventional access (36P in 126 ESI). While 10 of the 36 episodes of simultaneous
      infection in the conventional technique were caused by same organisms, none of
      the 2 episodes with the new access technique was caused by same organisms.
      CONCLUSION: The results of this study suggest that the new access technique
      reduces P incidence by virtually eliminating infection by the periluminal route.

PMID- 1361811
TI  - Choline levels in human peritoneal dialysate.
AB  - The average free choline level was determined to be 14 M in peritoneal dialysates
      and 22 M in plasma of thirty patients on continuous ambulatory peritoneal
      dialysis (CAPD). Daily choline loss via dialysate averaged 129 moles with 32
      moles choline lost per dwell. Daily choline loss via the dialysate was positively
      correlated with plasma choline concentrations. Choline levels in dialysate during
      CAPD exceed plasma levels of choline (9 M) in healthy individuals.

PMID- 1361812
TI  - Treatment of relapsing peritonitis in pediatric patients on peritoneal dialysis.
AB  - Relapsing peritonitis is often due to bacterial colonization of the Tenckhoff
      catheter and may require removal of the catheter in patients on peritoneal
      dialysis. The efficacy of a Tenckhoff catheter decontamination procedure was
      examined in 9 pediatric patients aged 1.5-18 years and compared to the outcome of
      a historical control group. After repeated dialysate cultures had become negative
      and cell count was normalized (< 100/ul), intraluminal urokinase (5000 IU/ml) and
      intraluminal high concentrated antibiotics (vancomycin, fosfomycin, cefotaxim)
      were instilled sequentially for 3 h and 1 h respectively. This procedure was
      performed once daily for three days. In addition, the connector was exchanged on
      the last day. This regimen prevented relapsing peritonitis in all study patients,
      whereas in the control group in 75.8% of events further relapses occurred,
      necessitating removal of the Tenckhoff catheter in 7/19 (36.8%) episodes. No side
      effects of intraluminal urokinase were recorded in any of the patients. We
      conclude that intraluminal urokinase and intraluminal high concentrated
      antibiotics combined with connector device exchange are highly effective for
      prevention of further relapses of peritonitis and reduce the need for Tenckhoff
      catheter exchange.

PMID- 1361813
TI  - CAPD disconnect systems: UK peritonitis experience.
AB  - We reviewed peritonitis (P) experience of four UK units using single use Y
      (Freeline T.M., Baxter UK)(F) and Twinbag (Solo T.M., Baxter UK) (S) disconnect
      systems, which incorporate the 'Flush Before Fill' principle. We aim to show
      clinical achievements, in varying circumstances, in the light of previously
      published in vitro study results. Each unit recorded P data, i.e., rates,
      causative organisms, and recurrences (R) over a 12 month period (Sept 89-Aug 90).
      This data was then analysed by system, by unit and in total. Each unit had
      similar definitions for P and R, but had varying system selection criteria. Unit
      1 had a fairly open criteria for F use, then became more selective at the same
      time as introducing S. In unit 2, F, and then S, were first choice systems for
      all (inc. blind diabetics). Unit 3 trains every pt. on non-disconnect System 2,
      then pt. choice determines if they are retained onto a disconnect system. Unit 4
      had a more highly selected population. Results, expressed as episodes/patient
      month, were as follows: [table: see text] We conclude that it is possible to
      achieve a low incidence of P, especially that caused by S. epidermidis,
      particularly with S. It would seem the extent is related to pt. to system
      selection criteria. The effects of R and ES/TI need to be addressed.

PMID- 1361814
TI  - A randomized multicenter trial to evaluate the effects of UV-Flash system on
      peritonitis rates in CAPD.
AB  - A number of systems and devices have been developed to reduce peritonitis in CAPD
      patients. One of the newer developed systems in the UV-Flash. A retrospective
      study was conducted in five Japanese hospitals to measure the efficiency of the
      UV-Flash system in reducing the peritonitis rate for CAPD patients. This study
      took place between January 1983 to January 1992. The UV-Flash system had a
      significantly lower peritonitis rate (1/46.6 patient months) compared to the
      Standard system (1/27.5), but showed nominal significance when compared to the
      Disconnect system (1/47.6). Due to the lack of differentiation in peritonitis
      rates between the UV-Flash and Disconnect system, patient types for both systems
      were analyzed. The study found more impaired patients on UV-Flash (37.2%) as
      opposed to the Disconnect (9.8%). These impaired patients treated on the UV-Flash
      system showed a significantly lower peritonitis rate (1/27.5) when compared to
      the Disconnect (1/9.7) system. The UV-Flash system proved able to achieve
      sufficient prevention of peritonitis in CAPD patients. Thus, this system can be
      successfully applied to high risk CAPD patients.

PMID- 1361815
TI  - Swan neck presternal ("bath tub") catheter for peritoneal dialysis.
AB  - We hypothesize that the swan neck catheter for peritoneal dialysis with exit in
      the presternal area will have better exit site healing and a decreased incidence
      of exit site infection than currently used peritoneal dialysis catheters with the
      exit located on the abdomen. The chest is a very stable structure, with minimal
      wall motion, especially of the upper chest and over the sternum. Hence, a
      catheter exit located on the chest will be subjected to only minimal movement.
      Decreased piston like movement of the catheter at the exit site reduces inward
      transfer of outer microbial flora. Moreover, a tight garment is usually not worn
      on the chest and there is less pressure on the exit. Based on this rationale a
      new catheter (swan neck presternal) has been designed. The presternal peritoneal
      dialysis catheter is composed of two flexible (silicon rubber) tubes joined
      through a titanium connector at the time of implantation. The device has been
      dubbed as a "bath tube" catheter because, with the exit on the chest, a patient
      may take a tub bath without the risk of exit contamination due to submersion. Two
      such catheters were implanted in two patients. One patient had multiple problems
      (including chronic exit site infection) with a previously implanted swan neck
      Missouri 2 catheter, the other patient was originally rejected as a peritoneal
      dialysis candidate due to extreme obesity. Both catheters healed well in 6 weeks
      and the exits have not become infected during the first 8 months. These
      preliminary experiences with 2 catheters support the rationale of their design.

PMID- 1361816
TI  - Exit-site/tunnel infection and catheter outcome in peritoneal dialysis patients.
AB  - STUDY OBJECTIVE: To study exit-site/tunnel infections and catheter outcomes in
      peritoneal dialysis patients. DESIGN: The study was designed to investigate exit
      site (ESI)/tunnel infections (TI) and catheter losses in all chronic PD catheters
      inserted in ESRD patients from 9/88 to 9/91. SETTING: Tertiary-referral
      university hospital. PATIENTS AND METHODS: Seventy-three patients (40 males, 33
      females) underwent 78 double-cuff coiled swan-neck catheter implantations
      surgically. The curettage of exit site was performed weekly for tunnel infection
      refractory to medical management. The subcutaneous cuff was excised in persistent
      ESI/TI. RESULTS: Fifty-nine episodes of ESI/TI in 34 patients were observed over
      946 patient-months. Thirty-nine patients experienced no ESI/TI, 27 patients had
      one and seven had two or more episodes of ESI/TI. Four patients had five episodes
      of peritonitis associated with ESI/TI. Eight recurrent episodes of ESI/TI with S.
      aureus in 8 patients were treated successfully with Rifampin. Seven subcutaneous
      cuffs were excised successfully in 7 patients with tunnel infection, five with S.
      aureus and two with Pseudomonas aeruginosa. No catheter was removed due to ESI/TI
      or ESI/TI associated peritonitis. CONCLUSIONS: Aggressive exit site care
      including repeated curettage, excision of the subcutaneous cuff and appropriate
      antibiotics reduced significantly catheter losses related to ESI/TI.

PMID- 1361817
TI  - Effect of simvastatin in CAPD patients with hypercholesterolemia.
AB  - The effect of simvastatin on serum total and HDL cholesterol and total
      triglyceride levels in 20 hypercholesterolemic patients on CAPD treatment was
      studied. The drug was given at the initial dose of 10 mg/day which was doubled up
      to 40 mg/day. Two non-compliant patients stopped the drug in the first week of
      treatment. One patient had vomiting and stopped simvastatin. One patients reduced
      the dose from 20 to 10 mg/day because of increase in CPK level. The study was
      completed in 16 patients. Serum cholesterol decreased from 318 +/- 39 to 208 +/-
      34 mg/dl (p < 0.001), triglyceride from 317 +/- 129 to 278 +/- 160 mg/dl and HDL
      cholesterol from 43 +/- 13 to 35 +/- 11 mg/dl. The effective does was 10 mg/day
      in 4 cases, 20 mg/dl in 7 and 40 mg/dl in 5. In CAPD patients, simvastatin is
      safe and effective in lowering serum cholesterol. The clinical significance of
      the decrease in HDL cholesterol and its possible effect on clinical outcome are
      still unknown.

PMID- 1361818
TI  - Is weight gain inevitable in most chronic peritoneal dialysis patients?
AB  - In order to determine the long-term effects of continuous peritoneal dialysis on
      weight, 100 consecutive patients entering our program in 1988 were studied and
      followed for a maximum of 36 months. All patients underwent monthly evaluations
      including weight and biochemical surveys. Peritoneal equilibration tests were
      performed in 75 patients. A definite and significant trend was noted for weight
      gain during the first 17 months with a mean weight gain of 6.41 +/- 8.36 kg or
      6.4% increase (p < 0.01). This was followed by a downward trend with a nadir on
      month 21 (p < 0.05). There were no significant differences in the change in
      weight for small or large patients. A positive correlation was noted between
      weight change and D/P creatinine at 12 and 24 months. Albumin concentrations
      remained stable throughout the period of observation. Serum albumin did not
      correlate with percent weight change nor with D/P creatinine. The frequency of
      peritonitis did not influence weight change in this population. The data suggest
      that there is marked interpatient variation, but the majority of patients on
      chronic peritoneal dialysis experience significant weight gain upon initiation of
      therapy. The trend is reversed after approximately 1.5 years of therapy raising
      the question of underdialysis due to loss of residual renal function or from
      patient selection after transfer of the healthier patients to transplantation
      and/or hemodialysis.

PMID- 1361819
TI  - Growth hormone responses to pituitary and hypothalamic stimuli in CAPD patients
      treated with recombinant human erythropoietin.
AB  - Several alterations of growth hormone (GH) secretion have been described in
      patients with chronic renal failure. The effect of chronic treatment with
      recombinant human erythropoietin (rHuEPO) on GH secretion in uremic patients
      undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The
      purpose of this study was to assess the GH responses to both direct and
      hypothalamic stimuli in CAPD patients chronically treated with rHuEPO. Eight
      clinically stable and well-nourished patients (age 19-59 yr) treated with
      subcutaneous rHuEPO, 96.5 +/- 72.1 U/kg/week, during 6-25 months were tested with
      GH-releasing hormone (GHRH, 100 micrograms iv in bolus). Insulin-induced
      hypoglycemia (0.1 U/kg iv in bolus) and clonidine (0.15 mg/m2 po) were used as
      indirect stimuli for GH release. Baseline concentrations of insulin-like growth
      factor I (IGF I) concentration was also determined. Five CAPD patients matched
      for age and sex and not previously treated with EPO were studied as a control
      group. There was no statistically significant difference in baseline IGF I
      concentrations in EPO treated patients in comparison with control group (2.6 +/-
      0.7 vs 0.9 +/- 0.3 U/ml). GHRH administration was followed by a GH release in the
      treated group that did not differ significantly from that obtained in controls
      (peak: 10.6 +/- 3.7 vs 15.2 +/- 7.8 micrograms l, area under the curve [AUC]:
      16.3 +/- 5.6 vs 24.0 +/- 11.4 micrograms.h/l).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361820
TI  - Metabolic differences between persistent and routine peritonitis in CAPD.
AB  - Changes in 10 metabolic parameters (body weight, blood hemoglobin, and serum
      albumin, urea, creatinine, cholesterol, triglycerides, potassium, calcium and
      phosphorus) were compared in 28 episodes of routine peritonitis and 27 episodes
      of persistent peritonitis. These infections occurred in 20 CAPD patients, all of
      whom acquired both types of peritonitis on separate occasions. Coagulase-negative
      staphylococci predominated in the routine infections, while Staphylococcus aureus
      and Gram-negative bacilli, especially Pseudomonas, were associated with
      persistent peritonitis. Decreases during infection were significantly larger in
      persistent as compared with routine peritonitis episodes for all 10 nutritional
      parameters. Time required for recovery of all nutritional variables except serum
      potassium and urea was significantly longer in the persistent episodes.
      Persistent peritonitis led to peritoneal catheter loss in 13 of the 27 episodes
      and was associated with 4 deaths, while routine peritonitis was associated with
      neither catheter loss nor death. In contrast to routine peritonitis, persistent
      CAPD peritonitis is associated with severe malnutrition, considerable morbidity,
      and mortality.

PMID- 1361821
TI  - Bone mineral and aluminum concentrations in patients undergoing CAPD.
AB  - CAPD results in continuous peritoneal transfer of hormones and minerals involved
      in the pathogenesis of renal osteodystrophy (RO). Moreover, although CAPD
      patients seem to have better control of serum phosphate concentration than
      hemodialysis patients, the need for aluminum-containing phosphate binders (ACPB)
      may still be present. In a prospective study meant to investigate the evolution
      of RO, we obtained 79 bone biopsies in 29 uremic patients (20 male, 9 female; age
      25-59, mean 46). Of these, 22 were obtained at the beginning of treatment, 24
      after 24 months, 23 after 36 months and 10 after 60 months. All patients were
      treated with CAPD (Viaflex, Baxter 2-2.5 L x 4-5 bags/day; Ca(++) + 3.5, Mg(++)
      1.5 mEq/L) as the first modality of therapy and received oral calcitriol,
      aluminum hydroxyde and/or calcium carbonate and magnesium hydroxyde in order to
      maintain serum calcium (Ca) and phosphorus within the normal range. Qualitative
      bone histology, bone Ca and magnesium (Mg) (Flame atomic absorption spectroscopy)
      and aluminum (Al) concentration (Graphite furnace atomic absorption spectrometry)
      were determined. CAPD achieves a good control of RO as indicated by the tendency
      toward a decreased incidence of mixed osteodystrophy and predominant
      hyperparathyroid bone disease and improvement of osteoid lesions. A defective Ca
      content of bone is persistent in the observed period and positively correlated to
      bone Mg concentration. An increased level of Al was shown in the serum and bone.
      The highest bone Al content was found among patients with predominant osteoid
      bone disease. Also in CAPD, patients consuming ACPB are at risk of bone Al
      accumulation despite the low Al levels in the dialysate.

PMID- 1361822
TI  - CAPD with low calcium dialysate and calcium carbonate: results of a 24-week
      study.
AB  - Twelve patients (median age 44.5 years) on CAPD, who had previously used a
      dialysate calcium concentration of 1.75 mmol/l (for a median time of 11.5 months)
      were started on a low calcium dialysate (LCD) with a calcium concentration of
      1.25 mmol/l and followed up for 24 weeks. During the first eight weeks, no
      changes in the doses of oral phosphate binders were made and serum ionized
      calcium decreased from 1.30 +/- 0.02 (mean +/- SE) mmol/l to 1.17 +/- 0.02 (p <
      0.0001) and serum PTH (1-84) rose from 68 (median, range 16-397) ng/l to 147 (70
      449, p = 0.005). After week 8, increasing doses of calcium carbonate were used to
      achieve target calcium levels of 1.20-1.30 mmol/l. No aluminum-containing binders
      were used. Calcium carbonate doses were increased from 2.3 (median, range 0.75
      12) g/d to 6.8 (3.8-15.0, p = 0.0004) and serum phosphorus concentrations
      decreased from 2.00 mmol/l (median, range 1.25-2.67) at 8 weeks to 1.61 (1.18
      2.39) at 24 weeks (p = 0.023). Serum intact PTH(1-84) values remained elevated
      despite the gradually increasing serum calcium concentrations. Hypercalcemia was
      recorded in 20/36 (56%) of blood samples during a period of four weeks before the
      start of LCD, and such episodes were observed in 15/89 (17%) of samples (p <
      0.001) on LCD during the period when calcium carbonate doses were increased. It
      is concluded that on LCD 1) the number of episodes of hypercalcemia was markedly
      reduced, 2) higher calcium carbonate doses could be used, and thus 3) the control
      of serum phosphorus improved.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361823
TI  - Lovastatin in the treatment of hypercholesterolemia in CAPD.
AB  - The authors studied the effect of lovastatin on five hypercholesterolemic CAPD
      patients with high risk of atherosclerotic cardiovascular disease. Patients took
      lovastatin 20 mg once daily for a mean period of 4.5 months. Pre- and post
      treatment values of LDL and VLDL totals (325 mg/dl and 292 mg/dl, respectively)
      and of HDL (42 mg/dl and 43 mg/dl, respectively) had no significant statistical
      difference. Lack of significance may be due to low number of patients and short
      trial time. The study did demonstrate that lovastatin is well tolerated in CAPD
      patients.

PMID- 1361824
TI  - Calcium, magnesium mass transfer and lactate balance study in CAPD patients with
      reduced calcium/magnesium and high lactate dialysis fluid.
AB  - We studied calcium (Ca), magnesium (Mg) mass transfer (MT) in 10 and lactate
      balance in 5 CAPD patients using standard dialysis solution [(ST) (Ca 1.75
      mmol/l; Mg 0.75 mmol/l; lactate 35 mmol/l)] and with reduced Ca/Mg, high lactate
      solution [(LC) (1.25 mmol/l; 0.25 mmol/l; 40 mmol/l respectively)]. Exchanges
      were performed with 1.36% and 3.86% glucose solutions. MT was calculated as
      mmol/exchange. Ca MT was +0.96 and +0.39 with ST 1.36% and 3.86% glucose
      respectively. Serum ionised Ca (iCa++) levels were less than fluid Ca during
      these exchanges. With LC 1.36% glucose it was -0.66 when ICa++ was more than
      dialysate Ca, but +0.66 when iCa++ was less than dialysate Ca. Ca MT was negative
      with LC 3.86% glucose irrespective of iCa++ levels. All patients were
      hypermagnesaemic (mean 1.24 mmol/l. Mg MT was +0.21 and -0.04 with ST 1.36% and
      3.86% glucose respectively and -0.62 and -1.13 with LC 1.36% and 3.86% glucose
      respectively. The difference between mean lactate gain and bicarbonate loss was
      less (-0.4) during exchange with LC 1.36% glucose. Mean plasma TCo2 and plasma pH
      did not differ between ST and LC solutions. We conclude that reduced Ca/Mg, high
      lactate solutions should reduce hypercalcaemia/magnesaemia and maintain a better
      acid base balance in CAPD patients who may require Ca/Mg containing phosphate
      binders.

PMID- 1361825
TI  - Beta 2 microglobulin in CAPD.
AB  - The peritoneal clearance (Kp) and renal clearance (Kr) of beta 2 microglobulin
      (beta 2 m) were studied prospectively on 50 ESRD patients treated with CAPD, in
      order to determine the effect of the number of daily exchanges on Kp and to
      investigate the factors which influence the serum levels of beta 2m. Kr and Kp of
      beta 2m and creatinine (Cr) were calculated using standard formulae at the
      initiation of study and again at 6, 12, 18 and 24 months by collecting 24 hour
      urinary output and dialysate effluent. Kp of beta 2m of patients on 3
      exchanges/day was .94 +/- .08 ml/min at the initiation of study and 1.1 +/- .08
      at the end. For patients on 4 exchanges/day it was .99 +/- .14 ml/min and 1.1 +/-
      .12 respectively. There was no significant difference. Serum levels of beta 2m
      were lower on patients with significant residual renal function (RRF) (17 +/- .9
      mg/L) than on patients without RRF (38 +/- 2 mg/L. p = .001). Serum levels of
      beta 2m correlated inversely with Kr of Cr and beta 2m at the initiation of study
      and at the end (r = .67 and .77 respectively, p = .0001). We conclude that serum
      levels of beta 2m correlate inversely with Kr of Cr and are expected to rise as
      RRF decreases. The combined peritoneal and renal excretion of beta 2m is less
      than its daily production. The number of dialysis exchanges does not influence Kp
      of beta 2m.

PMID- 1361826
TI  - Evolution of lipid profiles in long-term peritoneal dialysis.
AB  - Serial lipid profiles of 102 patients starting chronic ambulatory peritoneal
      dialysis (CAPD) in our renal unit from January 1985 to December 1990 were
      collected retrospectively. Transient triglyceride elevation was noted during the
      first two years of CAPD but declined to normal levels even lower than those at
      baseline by 60 months. Total cholesterol, HDL and LDL cholesterol levels did not
      change significantly. Lipid-lowering agents were begun in 17 patients before
      initiating CAPD, 5 of whom achieved lipid profiles warranting cessation of
      therapy. Five other patients started treatment while on CAPD. No statistical
      difference in patient mortality was found when patients hyperlipidemic at the
      initiation of CAPD were compared to their normolipemic counterparts. We conclude
      that the return to normal plasma triglyceride levels after transient triglyceride
      elevation during long-term CAPD implies that adaptative mechanisms of
      triglyceride production in response to chronic glucose overload may ensue.

PMID- 1361827
TI  - Low turnover bone disease is the more common form of bone disease in CAPD
      patients.
AB  - CAPD is considered a risk factor for low turnover bone disease. This was
      previously attributed to aluminum accumulation. We evaluated by biochemical and
      histomorphometric parameters (including double tetracycline labelling), 26
      patients maintained on CAPD for 12-14 months. Three (11.5%) showed mild
      hyperparathyroidism, 5 (19.2%) osteitis fibrosa, 3 (11.5%) mixed forms, 4 (15%)
      osteomalacia and 11 (42.3%) adynamic bone disease. Only one patient with diabetes
      mellitus showed an aluminum stained bone surface > 10%. Intact PTH serum levels
      were lower in LTBD (133.2 +/- 128 vs 468.2 +/- 451 pg/ml; p < 0.05). We also
      evaluated prospectively 11 patients who underwent a bone biopsy at start of
      dialysis and after 12 months of CAPD treatment. Bone biopsies pre CAPD
      demonstrated normal-high bone turnover disease in 8/11 (72.7%) and low turnover
      bone disease in 3/11 (27%). In the follow-up biopsies, 2 patients showed osteitis
      fibrosa and other two mild forms. Low turnover bone disease was found in 7
      patients (3 osteomalacia and 4 adynamic bone disease). We conclude that the
      predominant bone lesion in our CAPD patients is low turnover bone disease,
      predominantly adynamic forms, and aluminum does not seem to play a role on its
      genesis. Low intact PTH serum levels may be a predictor of low turnover bone
      disease.

PMID- 1361828
TI  - Effect of lovastatin on hypercholesterolemia in chronic renal failure.
AB  - Using a mouse model of chronic renal failure (CRF), the possibility of using
      lovastatin to treat hypercholesterolemia associated with CRF was examined. Renal
      failure was induced in 5 week-old, C57BL/6J mice by electrocoagulation of the
      right kidney surface followed by left nephrectomy 2 weeks later. Five weeks post
      nephrectomy, BUN and serum total cholesterol levels were assessed and lovastatin
      treatment commenced. Upon sacrifice 4 weeks later, BUN, serum total cholesterol
      levels and hepatic HMG-CoA reductase activity were measured. Results showed that
      CRF induced significant increases in serum total cholesterol levels and enzyme
      activity. Treatment with lovastatin led to a dose-dependent reduction in serum
      total cholesterol levels without affecting the enzyme activity. These results
      suggest that the hyper-cholesterolemia in CRF is partly due to an increase in de
      novo cholesterol synthesis in the liver and that the lipid-lowering effect of
      lovastatin is mediated by an action other than the direct reduction of hepatic
      HMG-CoA reductase activity.

PMID- 1361829
TI  - Low calcium (2.5 mEq/l) and high calcium (3.5 mEq/l) dialysate in peritoneal
      dialysis patients.
AB  - STUDY OBJECTIVE: To compare the effects of low-calcium and high-calcium dialysate
      in stable ESRD patients on peritoneal dialysis (PD). DESIGN: Dialysate containing
      2.5 mEq/l and 3.5 mEq/l calcium in combination with oral calcium salts as
      phosphate binders were evaluated. SETTING: Tertiary-referral university hospital.
      PATIENTS AND METHODS: Fifteen patients (6 male, 9 female) on low-calcium (2.5
      mEq/l) and 15 patients (6 male, 9 female) on high-calcium (3.5 mEq/l) dialysate
      were studied for 6 months. All patients received calcium acetate or calcium
      carbonate to control hyperphosphatemia before the study. RESULTS: Serum calcium,
      phosphorus and albumin did not differ before and after between the two groups.
      Three patients in low-calcium and five in high-calcium group developed
      hypercalcemia. Three in low-calcium group and four in high-calcium group required
      sucralfate to control hyperphosphatemia and hypercalcemia. Mean dose of elemental
      calcium was 1152 mg/day in low-calcium group and 790 mg/day in high-calcium
      group. A negative correlation (r = -0.82, p < 0.005) was observed between serum
      calcium and PTH at the end of study period in the low-calcium group. No such
      relationship was observed in the high-calcium group. CONCLUSIONS: Degree and
      frequency of hypercalcemia appeared similar with low-calcium and high-calcium
      dialysate in peritoneal dialysis patients.

PMID- 1361830
TI  - Increased uptake of radio labelled white blood cells into abdomen of uremics on
      peritoneal dialysis.
AB  - Peritonitis and exit-site tunnel infection are frequent causes of CAPD drop out.
      We studied 9 patients, 8 treated by CAPD and 1 by IPD. These patients underwent
      sonographic and scintigraphic study of the abdomen. All scintigraphic
      examinations showed a visceral uptake. In two cases, sub-clinical bowel
      inflammation, demonstrated by scintigraphic study, preceded a gram negative
      peritonitis. The scintigraphic study with radiolabelled white blood cells may be
      useful in identifying chronic aseptic inflammations and some bowel and exit-site
      conditions which are possible risk factors in some cases of peritonitis.

PMID- 1361831
TI  - Gastrostomy buttons for feeding children on continuous cycling peritoneal
      dialysis.
AB  - The promotion of growth in infants and young children with chronic renal failure
      (CRF) requires an aggressive approach to feeding, often in combination with early
      dialysis. Supplementary feeding has usually involved the use of nasogastric
      tubes, but these can have many problems. We report our experience with a
      gastrostomy button device (Bard Ltd.) for long term feeding. Ten children (7
      male) had an initial gastrostomy catheter inserted at a median age of 2.0 years
      (range 0.25-8.5 years). None of the children required an operation for
      gastrooesophageal reflux and 6 had placement of the gastrostomy catheter at the
      time of insertion of the Tenckhoff catheter for continuous cycling peritoneal
      dialysis (CCPD). The catheter is usually exchanged for a similar sized (18 gauge)
      button device after 4 weeks. All ten children received CCPD in addition to
      overnight feeding using an enteral feeding pump. The buttons have been in use for
      a mean of 12 months (range 2-33 months) and are only changed if the anti-reflux
      valves fail. Nutritional goals have been achieved and growth parameters
      maintained or improved in 9 children. The button has many advantages over
      nasogastric tubes or gastrostomy catheters. It has been welcomed by our families
      in reducing the stress of feeding these young children.

PMID- 1361832
TI  - Micronutrient supplementation in children on continuous cycling peritoneal
      dialysis (CCPD).
AB  - Data on the micronutrient (vitamin and trace mineral) requirements of children on
      chronic peritoneal dialysis is limited. Few preparations are of suitable content
      and palatability. In a prospective study we have assessed and compared the serum
      levels and dietary intakes of micronutrients (vitamins A, E, B12, folate and
      zinc, copper, iron) in 7 children on CCPD who were receiving either Ketovite
      tablets (vitamins C, E and B complex) and Cholecalciferol or a more comprehensive
      supplement, Paediatric Renal Seravit (vitamins A, E, D, C and B complex with
      trace minerals). All children received nutritional supplements orally or via a
      gastrostomy button. These supplements contributed significantly to their
      nutritional intakes. The mean dietary intakes of the studied micronutrients, with
      the exception of vitamins A, E, B12 and folate, were below RDA (USA) values. The
      Renal Seravit was tolerated by only 5 of the 7 patients. There was no significant
      difference in serum levels of the micronutrients while on the Paediatric Renal
      Seravit compared to Ketovite. Serum iron levels remained low on both supplements.
      A comprehensive micronutrient supplement may still be required in children on
      prolonged dialysis.

PMID- 1361833
TI  - Adequacy of solute and water removal in children treated with nightly
      intermittent peritoneal dialysis.
AB  - Nightly intermittent peritoneal dialysis (NIPD) is an automated form of
      intermittent peritoneal dialysis which has potential medical and psychosocial
      advantages in comparison with CAPD/CCPD due to the lack of daytime exchanges.
      Data on solute/water removal in children on NIPD are nevertheless scarce, so that
      no clear indications for NIPD can yet be formulated in pediatric age. For this
      reason, 12 patients, mean age 10.49 +/- 5.81, mean body weight 23.73 +/- 10.92,
      with a residual creatinine clearance 1.70 +/- 2.30 ml/min/1.73 sqm, on NIPD for
      14.7 +/- 5.4 months, underwent clearance studies over 3 days. Mean dialysis
      infusion volume was 460.08 +/- 196.30 ml/kg/day, with 10.33 +/- 1.22 h dialysis
      time. Peritoneal creatinine and urea clearances were 6.36 +/- 2.96 and 8.49 +/-
      3.35 1/day/1.73 sqm, respectively. Combined creatinine and urea clearances
      averaged 6.12 +/- 2.21 and 6.96 +/- 2.16 ml/min/1.73 sqm, resulting in serum
      creatinine and urea values of 7.78 +/- 1.90 and 115.58 +/- 29.93 mg/dl,
      respectively. Ultrafiltration rate was 16.94 +/- 16.34 ml/g glucose absorbed.
      NIPD provided similar or improved solute and water clearances compared with those
      reported in children and adults on CAPD/CCPD, without inconvenient long periods
      in bed. These data indicate that NIPD is a suitable treatment in pediatric end
      stage renal disease.

PMID- 1361834
TI  - Continuous peritoneal dialysis in children.
AB  - During the period from June 1985 to December 1991, 48 children were treated with
      continuous peritoneal dialysis (CPD) in our centre because of acute renal
      failure. The median age was 1.8 years (range 0.01-17.1). The most common
      diagnoses were: hemolytic uremic syndrome (n = 22), anuria after cardiac surgery
      (n = 7), and septicemia with multiorgan failure (n = 7). Kidney function
      recovered in 35 (73%); 13 (27%) died of their original disease. One further
      patient with HUS recovered from dialysis but died of cerebral complications
      shortly afterwards. One patient remained anuric and requires renal replacement
      therapy. Hyperkalemia, when present initially, and uremia could be controlled
      adequately in all cases. However, ultrafiltration posed problems when cardiac
      output was low. Peritonitis occurred in 11 patients; in 8 children the Tenckhoff
      catheter had to be revised because of leakage (5), flow problems (2), or bowel
      perforation (1). CPD proved to be an excellent method to treat acute renal
      failure in children of all age groups. The rate of complications was acceptable.

PMID- 1361835
TI  - Evaluation of peritoneal solute transfer by the peritoneal equilibration test in
      children.
AB  - To evaluate the characteristics of peritoneal kinetics in the young, we
      investigated solute and water transfer rates by a modified Peritoneal
      Equilibration Test (PET) in 20 pediatric patients aged 1.9 to 19.8 years. 1000
      ml/m2 body surface area of a 2.3% glucose PD solution were instilled in the
      peritoneal cavity. Glucose, creatinine, urea, sodium, potassium and phosphate
      were measured in the dialysate (D), 7 times during 4 hours and in plasma (P)
      after 2 hours dwell time. At 4 hours, the mean (+/- SD) D/P ratio was 1.06 +/-
      0.16 for urea, 0.79 +/- 0.14 for creatinine, 0.82 +/- 0.21 for potassium, 0.92 +/
      0.04 for sodium and 0.79 +/- 0.30 for phosphate. Mean D/D0 of glucose was 0.36
      +/- 0.13. The 4-hour solute equilibration curves were analytically best
      approximated by logarithmic functions for urea (mean R2 = 0.983), creatinine (R2
      = 0.973) and potassium (R2 = 0.979), by a linear function for phosphate (R2 =
      0.964), and by an exponential model for glucose (R2 = 0.969). The linear or
      exponential regression coefficients were used to express the peritoneal solute
      transfer rates. Although the transfer rates of most solutes were correlated with
      each other, the individual variation of peritoneal permeability for different
      solutes was high. Close associations were observed between the glucose and
      creatinine transfer rates (r = 0.91, p < 0.0001) and between ultrafiltration rate
      and glucose (r = -0.90, p < 0.0005) and creatinine (r = -0.88, p < 0.005).
      Peritoneal permeability for all solutes tended to be inversely correlated with
      body size (urea transfer rate vs. height: r = 0.49, p < 0.05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1361836
TI  - Five years' experience of the Italian Registry of Pediatric Chronic Peritoneal
      Dialysis.
AB  - The results of the first 5 years' experience of the Italian Registry of Pediatric
      Chronic Peritoneal Dialysis (CPD) (1986-1990) are presented. Patients of less
      than 15 years of age at start of dialysis were enrolled and clinical data
      collected until the age of 19. The number of the dialysis centres participating
      in the Registry increased from 7 in 1986 to 15 in 1990. The total number of
      patients on CPD was 119, the number of new patients per year ranged from 15 to 28
      and the percentage of all dialysed children treated with CPD increased from 40%
      in 1986 to 49% in 1990. The age of patients at start of CPD was 8.5 +/- 4.9 years
      and 16% of them were under 2 years. Only CAPD was utilized in 1986, while
      CCPD/NPD accounted for 53% and 65% of the treated patients in 1989 and 1990,
      respectively. At 4 years, patient survival was 91.3% and technique survival
      79.3%. A comparison between data of 48 patients on CPD and 34 on hemodialysis,
      who started dialysis in the period 1989-1990, showed that CPD was the most
      frequent form of initial therapy (56%) and was the treatment of choice for
      children younger than 4 years.

PMID- 1361837
TI  - Peritonitis in children undergoing chronic peritoneal dialysis (CPD): data from
      the Italian Registry of Pediatric CPD.
AB  - During the period 1986-1990, 119 patients were enrolled in the Italian Registry
      of Pediatric CPD. CAPD was largely predominant in the first 3 years, while CCPD
      accounted for 48% of dialysis months in the period 1989-1990. The connect
      disconnect system was a Y set for all patients during the whole observation
      period. The incidence of peritonitis decreased from 1 episode: 10.9 patient
      months in 1986 to 1:19.8 in 1988, and then passed to 1:16.2 in 1990. A comparison
      of the incidence of peritonitis between CAPD and CCPD, referring to the 1989-1990
      period, showed no significant difference. The percentage of positive peritoneal
      fluid cultures changed from 48% in 1986 to 73% in 1990. Gram-positive bacteria,
      primarily Staphylococcus aureus and Staphylococcus epidermidis, accounted for
      most of the isolated organisms. Candida albicans was cultured in 3 cases both in
      1986 and 1987. Exit site infection was the predominant (82%) complication,
      followed by leakage and catheter cuff extrusion. The hospitalization rate for
      peritonitis resulted persistently high (61% of episodes) and the mean duration
      was 12.7 days. Of the 8 patients who were switched to hemodialysis, 4 had
      recurrent peritonitis and 1 Candida albicans peritonitis.

PMID- 1361838
TI  - Bicarbonate is not the ultimate answer to the biocompatibility problems of CAPD
      solutions: a cytotoxicity test of CAPD solutions and effluents.
AB  - Human polymorphonuclear granulocytes (PMN) were tested for migration and
      phagocytosis after exposure to CAPD solutions and effluents sampled during the
      first hour of dialysis from patients treated with lactate or bicarbonate based
      CAPD-solutions. The effluents from the lactate based solutions (Dianeal and
      Lockolys) reduced the migration and enhanced the phagocytosis compared to values
      obtained in a standard cell culture medium. Both cell functions increased during
      the dialysis period. In contrast, the cell-function only changed slightly when
      87b, a bicarbonate based CAPD-solution (pH = 7.4, [HCO3-) = 29mM), was employed.
      During the first 30 minutes, the cells performed at a higher level when exposed
      to the 87b effluent than when exposed to the lactate effluents. The observations
      further indicated that optimal conditions for PMNs are at a bicarbonate
      concentration of less than 20 mM and a lactate concentration of less than 15mM.
      IN CONCLUSION: PMN migration is reduced by both lactate and bicarbonate based
      CAPD solutions and effluents collected during the first hour of dialysis. The bio
      compatibility of CAPD solutions may be improved by combining the lactate and
      bicarbonate buffering systems in a solution with a concentration of less than 20
      mM of bicarbonate and less than 15 mM of lactate.

PMID- 1361839
TI  - Benefits of a mainstreamed summer camp experience for teens with ESRD.
AB  - This is a report on a pilot project integrating children with end stage renal
      disease (ESRD) with well children for a summer camp experience. As the teen with
      ESRD prepares to enter the work force and college, he/she will have to adapt to a
      variety of situations that will not adapt to his/her unique medical condition.
      These issues motivated a pilot project in which 9 ESRD children were mainstreamed
      into a 2 week, YMCA summer camp experience. Pre and post questionnaires were
      developed and distributed to the camper, family, and the cabin counselor along
      with interviews to assess the value of the experience. All the children left camp
      more independent and knowledgeable about their self-care. The results of this
      pilot project indicate that children with ESRD can adapt to their environment and
      increase independence, self-care and self-esteem through supervised mainstreamed
      experiences.

PMID- 1361840
TI  - Successful management of CAPD in infants with cardiac failure.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) was selected and introduced as a
      primary dialysis method in two infants with cardiac failure. CAPD was started at
      14 days after birth with body weight of 2125 gm and at 7 months of age with body
      weight of 2325 gm. In both cases, cardiac failure was due to large ventricular
      septal defect (VSD) and renal failure was due to dysplastic kidneys. In the first
      case (case 1), direct closure of atrial septal defect and patch closure of VSD
      were successfully completed at 9.5 months of age with body weight of 4844 gm.
      CAPD has been managed well for 1 year and 8 months and the child reached a body
      weight of 8440 gm. In the second case (case 2), CAPD was managed well for 11
      months with body weight increasing to 4920 gm at the age of 1 year and 7 months.
      This marked deterioration of this boy's physical growth was mainly caused by the
      delay in introducing CAPD and partly due to his cardiac dysfunction which has not
      been corrected surgically. Both cases show almost normal mental development and
      are managed well at home. Although CAPD introduction yielded water balance and
      physical growth in these infants, earlier introduction of CAPD may result in
      better clinical outcomes including management following open heart surgery.
      Selection of CAPD as a primary dialysis maneuver is strongly recommended for
      uremic infants with cardiac failure.

PMID- 1361841
TI  - Acute peritoneal dialysis utilizing a non-luminal channeled catheter in infants.
AB  - Acute peritoneal dialysis in unstable infants is at times plagued by early
      catheter malfunction secondary to omental plugging in both rigid acute catheters
      and conventional Tenckhoff catheters. This problem is inherent to the design of
      catheters using sideports for outflow and is enhanced by the tenacity of the
      omentum in this population in walling off foreign bodies. We have modified and
      utilized a non-luminal, channeled surgical drain for acute peritoneal dialysis in
      infants to avoid this problem. Five infants ranging in age from 2 days to 7
      months were dialyzed acutely in a Pediatric Intensive Care Unit setting for
      periods ranging from 5 to 34 days utilizing this modified catheter. The infants
      ranged in weights from 1.96 to 8 Kg. Catheters were placed by a surgeon and
      peritoneal dialysis was initiated using a Y-setup. In none of the patients was
      there loss of catheter function secondary to omental plugging. Three patients
      subsequently died of their underlying illness and two recovered renal function.
      Two acute catheters were subsequently changed to conventional Tenckhoff catheters
      when it became apparent that dialysis would need to be performed for a prolonged
      time. The acute catheter which was used has a four channel cloverleaf appearance
      when cut in cross section with no central lumen. There is a transition to a
      luminal catheter outside the peritoneal cavity. The advantage of the cloverleaf
      configuration is the ability to exchange fluid along its entire intraperitoneal
      length, thereby excluding a defined area of catheter sideports where omentum can
      occlude the system causing a ball valve phenomenon.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1361842
TI  - Could CAPD modulate the hemodynamic changes induced by rHuEPO treatment?
AB  - Hemodynamic response to treatment with erythropoietin has been analyzed on two
      different groups of patients. The first group of 25 patients was treated with
      hemodialysis. The second group of 27 was treated with peritoneal dialysis. Both
      groups were studied before starting the treatment with erythropoietin, after
      reaching the hemoglobin target point, and after one year of treatment. The
      following parameters were recorded: basal and hemoglobin target point, time and
      dosage of response, incidence of arterial hypertension, diastolic and systolic
      left ventricular diameters, interventricular septum and posterior wall thickness,
      ejection fraction, fractional fiber shortening, left ventricular mass index,
      cardiac output index and peripheral resistance index. The incidence of
      hypertension was 28.8% and, in both techniques, stabilization of left ventricular
      mass index occurred a year later. When the hemoglobin target point was reached, a
      decrease in cardiac output and an increase in peripheral resistance was found.
      These changes were more evident in the group of patients treated with HD. After a
      year of treatment, both peripheral resistance and cardiac output were similar to
      basal values in both groups of patients.

PMID- 1361843
TI  - Once weekly subcutaneous administration of recombinant erythropoietin in children
      treated with CAPD.
AB  - Treatment with rHuEpo can eliminate many symptoms that had been attributed to
      uremia. Repetitive punctures in children undergoing three times weekly
      subcutaneous (SC) rHuEpo can result in noncompliance with the therapeutic
      regimen. The aim of this study was to evaluate the efficacy of once weekly SC
      injection of rHuEpo in children with end-stage renal disease (ESRD) on CAPD. Six
      children (5 males, 1 female, mean-age: 6.0 years, range: 0.5 to 15.8 years) with
      ESRD on CAPD were treated with a regimen of rHuEpo 150 U/Kg/week SC for 12 weeks.
      All patients received oral iron supplementation. All children had improved
      appetite and well-being. The adolescents showed an increased ability to engage in
      regular activities. The hematocrit increased from 20.3 +/- 1.2% to 31.7 +/- 3.8%
      in 12 weeks. The mean weekly increase in hematocrit was 0.95 +/- 0.34%. There was
      no significant differences in iron indice prior to and during rHuEPO treatment.
      Side effects related to rHuEpo included transient pain at the site of injection
      in all, pruritus at the site of injection in 1 child, hyperphosphatemia in 1
      infant, iron relative deficiency in 2 children and an asymptomatic increase in
      blood pressure in 1 hypertensive child. None of the 5 normotensive patients
      developed hypertension. We concluded that once weekly 150U/kg SC rHuEpo is
      effective in correcting anemia in children on CAPD. This regimen results in few
      side effects, decreases the cost of treatment and produces less distress to the
      patients by avoiding repetitive injections.

PMID- 1361844
TI  - A prospective open-label study evaluating the efficacy and adverse reactions of
      the use of Niferex-150 in ESRD patients receiving EPOGEN.
AB  - Iron supplementation is usually required in patients receiving epoetin alfa.
      Ferrous sulfate is commonly prescribed, however many patients experience adverse
      gastrointestinal effects. Adverse effects may limit the amount of iron that can
      be prescribed, and may lead to noncompliance. Polysaccharide-iron complex (PIC)
      is an iron supplement containing greater amounts of elemental iron, and may
      produce fewer adverse effects. This study compared the efficacy and adverse
      effects of PIC to a historical period of treatment with ferrous iron salts to 38
      dialysis patients receiving epoetin alfa. All patients were switched to PIC, and
      were followed for six months. The following laboratory information was recorded:
      hematocrit, serum iron concentration, percent transferrin saturation, total iron
      binding capacity, serum ferritin concentration. Patients were given an adverse
      experience questionnaire at four and six months of PIC treatment. No differences
      in laboratory values were noted between treatments. The amount of prescribed
      elemental iron increased, while iron dextran use decreased during PIC therapy.
      Epoetin alfa doses were unchanged. Patients reported fewer gastrointestinal
      adverse effects at four months, however differences at six months were less
      striking. PIC is as effective as ferrous sulfate in sustaining erythropoiesis in
      patients receiving epoetin alfa. It may produce fewer adverse effects.

PMID- 1361845
TI  - Erythropoietin associated hypertension among pediatric dialysis patients.
AB  - The major side effect of rHuEPO is hypertension, which is reported to occur in 10
      75% of adult patients. The aim of the present study is to evaluate the effect of
      rHuEPO on blood pressure in pediatric dialysis patients. Nine CAPD patients (mean
      age 7.4 +/- 3.6 years) and fourteen HD patients (mean age 13.8 +/- 5.5 years)
      were treated with rHuEPO. The hematocrits increased significantly from 20.7 +/-
      1.8 to 28.3 +/- 4.1 in HD patients and from 19.7 +/- 2.9 to 26.7 +/- 4.4 in CAPD
      patients. The final maintenance dose required to correct the anemia was 47.6 +/-
      11.7 units/kg/week for CAPD patients and 122.6 +/- 75.2 U/kg/week foe HD
      patients. Six (66.6%) out of nine CAPD patients, and five (35.7%) of fourteen HD
      patients developed or worsened hypertension. Younger CAPD patients tended to
      develop hypertension. Correction of anemia was poor in two hypertension
      exacerbated patients, since rHuEPO dose increase was withheld for fear of
      aggravating hypertension. A four-year-old girl developed hypertensive
      encephalopathy after 13 months of rHuEPO therapy. No difference was observed in
      plasma level of aldosterone or plasma renin activity. Hypertension is observed
      frequently among pediatric dialysis patients treated with rHuEPO therapy. Careful
      monitoring and management of hypertension is required, especially in the first
      three months of rHuEPO therapy.

PMID- 1361846
TI  - Effects of erythropoietin-induced hemopoiesis on peritoneal transport and on in
      vitro T cell response in CAPD.
AB  - In order to investigate the therapeutic efficacy of subcutaneously administered
      erythropoietin (rHuEPO) and the effects of rHuEPO-induced hemopoiesis on
      peritoneal transport and on cellular immune responses, we performed standardized
      peritoneal equilibration tests and measured T cell subsets and phytohemagglutinin
      (PHA)-induced interleukin-2 receptor (IL-2R) expression of PBMC by flow cytometry
      before and after subcutaneous rHuEPO (Eprex-, Cilag), 4000 U twice weekly, in 13
      stable CAPD patients. Hct increased from 21.3 +/- 3.4% to 30.0 +/- 4.8% after 1
      mo and to 32.7 +/- 4.9% after 2 mon of rHuEPO. Drained volume after 4 hrs of
      dwell with 4.25% dialysate increased from 2,675 +/- 204 ml to 2,807 +/- 174 ml (P
      < 0.05). D4/P4 creatinine increased from 0.68 +/- 0.07 to 0.71 +/- 0.06 (P <
      0.05) and creatinine clearance from 7.57 +/- 0.71 to 8.03 +/- 0.63 ml/min (P <
      0.05). The number of total circulating lymphocytes, T4,T8, T4/T8 with or without
      PHA did not change after rHuEPO. PHA-induced IL-2R expression by PBMC as
      expressed by mean channel of fluorescence intensity increased from 149.8 +/- 6.7
      to 156.8 +/- 6.1 (P < 0.05). CONCLUSION: Subcutaneous rHuEPO is effective in
      correcting anemia in CAPD patients. rHuEPO-induced hemopoiesis is associated with
      increase in peritoneal creatinine and water transport and also with PHA-induced
      IL-2R expression.

PMID- 1361847
TI  - How does rHuEPO effect D/P creatinine ratios?
AB  - Initially starting CAPD patients on EPO was concerning after hearing reports of
      hemodialysis patients stating that they "may need more dialysis". The rationale
      given was that with a higher hematocrit the percentage of plasma in whole blood
      would decrease, leading to an increase of red cell mass. This decreased plasma
      volume and increased viscosity would lead to a slower blood flow ultimately
      resulting in less efficient dialysis. Assessing CAPD patients' peritoneal
      efficiency was the next step. We obtained pre and post-EPO PETs and evaluated.
      The initial results showed that D/P creatinine ratios were dropping as our Hcts
      increased, and ultrafiltration results projected an improvement. What remained
      unanswered was what took place over extended periods of time on EPO therapy. We
      examined twelve patients over a period of 27 months. Each patient received 4
      exchanges per day using 1500 to 2500 volume. PET tests were performed on each
      patient prestudy, and at months three, six, and 25-27. Initially each patient
      received EPO 4000 units, 3/week, SQ. EPO easily increased and maintained our
      patients' hematocrits within 12 weeks after starting the study. D/P creatinine
      ratios initially dropped but as our study continued there was a return of D/P
      creatinine ratios to 6% greater than baseline. One report suggests that EPO may
      have a direct vasoconstricting effects on blood vessels caused by the stimulation
      of calcium toward the cell. Vasoconstriction of the vessels would lead to a
      decrease in exchangeable surface area resulting in a decreased D/P creatinine
      ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361848
TI  - Effect of the correction of anemia with recombinant human erythropoietin on
      growth of children treated with CAPD.
AB  - Anemia correction with recombinant human erythropoietin (EPO) has been suggested
      to have a positive effect on nutritional status by improving appetite and protein
      metabolism. To assess this effect growth velocity and various parameters of
      nutritional status of 10 children on continuous ambulatory peritoneal dialysis
      (CAPD) were estimated at the start and one year after the correction of anemia.
      There was no significant improvement of growth velocity after EPO administration.
      Energy and protein intake, standard deviation scores of anthropometric
      measurements, BUN, serum creatinine, albumin, potassium, phosphorous and protein
      catabolic rate did not differ significantly before and after EPO administration.
      There was a significant correlation of protein intake and protein catabolic rate.
      CONCLUSION: There was no significant improvement of nutritional status and growth
      of children on CAPD treated with EPO, possibly because there was no evidence of
      malnutrition in most patients.

PMID- 1361849
TI  - Iron dextran treatment in peritoneal dialysis patients on erythropoietin.
AB  - STUDY OBJECTIVE: To evaluate maintenance parenteral iron dextran in chronic
      peritoneal dialysis (PD) patients receiving erythropoietin (rHuEPO). DESIGN:
      Parenteral iron dextran was investigated in PD patients with poor response to
      rHuEPO and/or side effects of oral iron. SETTING: Tertiary-referral university
      hospital PATIENTS AND METHODS: Seven ESRD patients (five males and two females)
      were studied. A test dose of 25 mg iron dextran was given before starting a
      maintenance dose. Iron dextran 100 mg was given intramuscular weekly or biweekly.
      Six patients received rHuEPO and one patient was on decadurabolin. RESULTS:
      Hematocrits increased significantly (p < 0.01) from 29 +/- 2% to 38 +/- 2% and
      serum ferritin increased from 267 +/- 104 to 660 +/- 104 ng/dl after iron
      dextran. Serum albumin increased from 3.1 +/- 0.3 to 3.6 +/- 0.2 g/dl (p < 0.05).
      No patient developed an anaphylactic reaction or delayed reaction. Mean duration
      of parenteral iron dextran treatment was 7 +/- 1 months. Mean dose of
      erythropoietin was reduced significantly (p < 0.05) from 119 +/- 20 units/kg/week
      to 87 +/- 20 units/kg/week before and during fifth month of iron dextran therapy.
      CONCLUSIONS: Weekly/biweekly maintenance intramuscular iron dextran injection was
      effective and safe iron supplemental therapy in PD patients with poor response or
      side effects to oral iron.

PMID- 1361851
TI  - Effect of CAPD dialysate on the release of eicosanoids and cytokines from human
      peritoneal macrophages.
AB  - The effect of fresh peritoneal dialysis (PD) solution and effluent on the
      generation of eicosanoids and cytokines by human peritoneal macrophages (PMO) was
      studied in vitro. PMO, isolated by density gradient separation from patients
      undergoing intermittent peritoneal dialysis (IPD), were incubated for 2 h with PD
      effluent after dwell periods of 5 to 240 min or fresh PD solution. Supplemented
      RPMI-1640 medium served as control. PMO were stimulated by calcium ionophore
      A23187 (10 M). PD solution significantly inhibited the release of prostanoids
      (PGE2, TXB2, 6-k-PGF1), leukotrienes (LTB4, LTC4), and cytokines (11-6, TNF) from
      PMO by 60 to 96% (p < 0.05). Addition of A23187 increased the generation of TXB2,
      LTB4, and LTC4 in PD solution adjusted to pH 7.4 to 2.7 up to 28.6 times the
      basal level, but was ineffective in PD fluid at pH 5.2. Incubation of PMO with PD
      effluent of varying dwell times resulted in a rise of all assayed mediators (p <
      0.05). The release of IL-6 increased continuously from 80 +/- 10 pg/10(6) PMO (0
      min dwell time) to 440 +/- 104 pg/10(6) PMO (4 h dwell time, mean +/- S.E.M.).
      TNF generation rose from 6.0 +/- 0.1 pg/10(6) PMO (0 min dwell time) to 162 +/-
      54 pg/10(6) PMO after 5 min dwell time and remained constant with effluents of
      longer dwell times (15 to 240 min). Exposure of PMO to PD effluents after 240 min
      dwell time tended to decrease the median levels of PGE2, TXB2, and 6-k
      PGF1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361850
TI  - Peritoneal dialysis efficiency in CAPD patients in treatment with rHuEPO.
AB  - Possible modifications in peritoneal behaviour that can be caused by
      erythropoietin (EPO) treatment and/or correction of anemia in the ultrafiltration
      and peritoneal diffusion were studied in 24 CAPD patients. The evolution of the
      patients on the medium run was also studied. The dialysate to plasma ratio, the
      peritoneal clearance and the mass transfer coefficient of urea and creatinine and
      the ultrafiltration volume were studied, baseline, after reaching the hemoglobin
      target, and after eight months of treatment. The group of patients developed a
      decrease in the dialysate to plasma ratio and in the peritoneal clearance of
      creatinine. After evaluating the effects of the hemoglobin and the hematocrit, we
      found a decrease in the dialysate to plasma ratio of urea and creatinine, and in
      the peritoneal clearance of creatinine. A decrease was also found in the mass
      transfer coefficients of urea and creatinine. An increase in the ultrafiltration
      was also found in the patients with hemoglobin levels higher or equal to 11 g/dl.
      Those changes are reversible after turning the hemoglobin levels back to levels
      lower than 11 g/dl.

PMID- 1361853
TI  - Clinical experience and comparative analysis of the standard and fast peritoneal
      equilibration tests (PET).
AB  - The fast peritoneal equilibration test (PET) has been proposed as a substitute
      procedure for the standard PET because it is less expensive and less time
      consuming since fewer samples must be drawn. This study was undertaken to compare
      the fast and standard PETs to determine if the fast PET is a viable alternative.
      Fifteen patients participated in the study. Results from the standard PETs
      indicate 13 patients had average permeability and 2 patients had high transport.
      Corresponding fast PETs indicate 10 patients with average permeability, 2
      patients with high transport, 1 patient had discrepancies between the D/P ratios
      and drain volume, and 2 patients were noncompliant and did not complete the fast
      PET. We conclude that the fast PET is a valid screening tool to evaluate
      peritoneal membrane permeability in patients who have previously undergone a
      standard PET. It is cost effective and timesaving. The test is easily invalidated
      if patients fail to comply with instructions for the test. The fast PET is
      primarily useful as a screening device to determine whether permeability has
      changed.

PMID- 1361852
TI  - Urea kinetics evaluation of hemodialysis and CAPD patients.
AB  - Urea kinetics have been used to measure adequacy of hemodialysis. The role of
      urea kinetics in CAPD has not been clearly established. Using urea kinetics, we
      studied 71 hemodialysis and 71 CAPD patients. Age was 53 +/- 12 and 45.8 +/- 12
      respectively. Urea kinetics in hemodialysis were studied in the standard manner.
      CAPD patients collected 24 hr, dialysate fluid to measure urea, creatinine,
      glucose and protein. Urine was collected for 24 hr. to measure urea and
      creatinine. Protein catabolic rate (pcr) was calculated from the total amount of
      urea cleared in 24 h. Both groups of patients had similar body weight. Kt/V in
      CAPD (0.65 +/- 0.1) was at a level considered underdialysis for hemodialysis. In
      both groups, pcr increased as Kt/V increased. However, CAPD patients had levels
      of pcr higher than hemodialysis patients at the same level of Kt/V. BUN, serum
      albumin and serum potassium were significantly lower in CAPD patients. Patients
      who dialyze more, eat more. Differences in protein intake may be due to a more
      liberal diet in CAPD, patient selection, removal of middle molecules, or better
      control of the acidosis.

PMID- 1361855
TI  - Urea kinetics has limited relevance in assessing adequacy of dialysis in CAPD.
AB  - The application of urea kinetics to CAPD is controversial. Additional data is
      presented from our recent study on this topic. Different methods of calculating
      KT/V and normalized protein catabolic rate (PCRN) are compared and KT/V is shown
      to be on average 6.5% higher when V is calculated by Watson's formulae instead of
      by body weight alone. This discrepancy increases with time. It is also shown that
      standard methods may overestimate KT and underestimate PCRN. KT/V and PCRN by
      these different methods do not correlate with clinical outcomes. However, if V is
      calculated by Watson's formulae, there is a significant excess of deaths when
      KT/V is under 0.5 (weekly KT/V under 1.5). Survival curves show that neither
      initial KT/V nor PCRN predict failure on CAPD.

PMID- 1361854
TI  - Marked improvement in parameters of renal osteodystrophy with the use of
      intraperitoneal calcitriol.
AB  - Parenteral administration of Calcitriol is felt to be superior to oral Calcitriol
      in the treatment of renal osteodystrophy in chronic renal failure patients. We
      analyzed the results of serum calcium, phosphorus, alkaline phosphatase, and N
      terminal parathormone level which are the clinical parameters of renal
      osteodystrophy in twenty-three chronic peritoneal dialysis patients who received
      varying dosages of intraperitoneal Calcitriol. The results which were analyzed at
      the end of one to twenty-three months revealed significant increase in serum
      calcium and a significant decrease in the values of alkaline phosphatase and N
      terminal parathormone level.

PMID- 1361856
TI  - Interactions of cells from peritoneal dialysate with mesothelial cells and
      fibroblasts in culture.
AB  - Peritoneal mesothelial cells and fibroblasts were co-cultured in vitro with
      peritoneal white blood cells (PWBC) obtained from CAPD patients, after an
      overnight exchange with 0.5% Dianeal or 2.5% Dianeal. Unstimulated PWBC inhibited
      proliferation of mesothelial cells and fibroblasts. Upon stimulation with
      lipoposaccharides (LPS), PWBC from the 0.5% dextrose exchange, enhanced the
      growth of mesothelial cells and fibroblasts, whereas when stimulated with LPS,
      PBWC from the 2.5% dextrose exchange increased only proliferation of fibroblasts.

PMID- 1361857
TI  - Hospitalization: CAPD versus hemodialysis and transplant.
AB  - We studied morbidity in 648 patients treated in our center in a ten-year period
      as indicated by duration of hospitalization: 232 patients were on CAPD, 188 on
      hemodialysis (HD) and 228 had cadaveric kidney transplants (Tx). Duration of
      hospitalization was divided into four groups according to its causes. The age of
      the patients on CAPD was 61 +/- 14 years, 53 +/- 17 on HD and 36 +/- 10 in the Tx
      group. The total follow-up was 629 patient-year (p-y) on CAPD, 458 p-y on HD and
      928 p-y on Tx. The first admission was longer on CAPD (30 +/- 18 days) and on Tx
      (36 +/- 18 days) than on HD (18 +/- 12). After the first admission, the total
      days of hospitalization (days/patient-year, d/p-y) were more for CAPD than HD and
      Tx. Analysis of these data showed that the difference was due to peritonitis and
      to the different percentage of elderly patients in the CAPD group. With a
      reduction in the incidence of infectious complications (peritonitis, tunnel or
      exit-site), hospitalization in CAPD could be reduced to a length of time similar
      to that currently needed by HD and Tx patients. This can result in important cost
      saving.

PMID- 1361858
TI  - Pulmonary function variation in ventilator dependent critically ill infants on
      peritoneal dialysis.
AB  - Four ventilator dependent infants on PD for acute renal failure underwent
      pulmonary function (PFT) evaluation at varying times in the PD cycle. Mid dwell
      peak intraperitoneal pressure (IPP) correlated with a significant decrease in
      pulmonary compliance and increase in air way resistance. This further correlated
      with a decrease in PO2 and an increase in PCO2 on arterial blood gas analysis.
      Etiology of the PFT changes appear to correlate most closely with IPP yet other
      factors including pulmonary artery shunting as well as hypercapnea secondary to a
      4.25% dialysate are being evaluated as additional causative factors.

PMID- 1361859
TI  - A review of urea and creatinine kinetics in predicting CAPD outcome.
AB  - The adequacy of the peritoneal dialysis prescription is of great concern.
      Although the use of urea kinetics has become the standard in hemodialysis, its
      usefulness in peritoneal dialysis is unclear. It has been suggested that
      creatinine clearance may correlate with clinical outcome in CAPD but, as with
      urea kinetics, its predictive value is not established. The efficacy number (EN),
      which only requires a four hour exchange, was introduced as a simpler approach to
      creatinine kinetics. These three kinetic models were correlated to clinical
      outcome in 18 stable CAPD patients over a 12 month study period. The patients
      were divided into three groups: good (G), intermediate (I), and poor (P) based on
      uremic symptoms, mortality, hospital days, biochemical indices and the need for
      transfer to hemodialysis. Both forms of creatinine kinetics (weekly creatinine
      clearance, EN) were able to differentiate between the G, I, and P outcome groups
      (P < 0.05). The weekly uea Kt/V was able to differentiate between the G and P
      groups (P < 0.05) but not between the I and the other two outcome groups. Both
      urea and creatinine kinetics predict clinical outcome in CAPD. However,
      creatinine kinetics may be a more sensitive predictor. The efficacy number was
      just as sensitive as creatinine clearance in predicting clinical outcome yet
      simpler to gather the data for its calculation.

PMID- 1361860
TI  - Nutritional status in long-term CAPD patients.
AB  - We studied normalized urea nitrogen appearance (NUNA), normalized protein
      catabolic rate (NPCR), and normalized daily creatinine excretion (NDCE) in twenty
      one patients (15 men, 6 women; mean age 63 +/- 9 years) on CAPD for more than 4
      years (80 +/- 27 months). In the same patients we evaluated the changes in serum
      albumin and transferrin with time. After 74 +/- 26 months on CAPD, NUNA was 0.12
      +/- 0.03 g/Kg IBW/day, NPCR = 1.09 +/- 0.19 g/Kg IBW/day; NDCE = 15.1 +/- 3.1
      mg/Kg IBW/day; serum albumin = 3.8 +/- 0.2 g/dl. NUNA was correlated with NPCR (p
      < 0.001) and both were correlated with NDCE (p = 0.007 and p = 0.008). NPCR
      significantly decreased as patient age increased (p = 0.007) but was not
      correlated with time on CAPD, sex or serum albumin. Serum albumin did not change
      as age increased. Serum albumin and serum transferrin had not significantly
      changed after 4 years (after 8 years in a subgroup of eight patients). Finally,
      we compared these data to the initial data recorded for the same patients (mean
      interval: 64 +/- 21 months). NUNA, NPCR and NDCE did not change significantly.
      Changes in NPCR were directly related to changes in NDCE (p = 0.019). This study
      supports that long-term CAPD does not necessarily impair nutritional status and
      suggests that the oldest patients can maintain stable serum albumin
      concentrations on lower protein intake than younger ones.

PMID- 1361861
TI  - Canada-USA (CANUSA) multicentre study of peritoneal dialysis adequacy:
      description of the study population and preliminary results. CANUSA Peritoneal
      Dialysis Study Group.
AB  - The adequacy of peritoneal dialysis should be defined by clinical outcomes.
      Studies using multivariate techniques to evaluate the effect of demographic and
      clinical risk factors on these clinical outcomes showed worse patient survival
      for age > 60 years, diabetes mellitus, history of cardiovascular disease, black
      race and prior ESRD therapy. The single study reporting a multivariate analysis
      of urea kinetics and these baseline prognostic factors on clinical outcome showed
      serum albumin to be the most powerful predictor of survival. A multicentre study
      (10 Canadian and 4 US Centres) has enrolled 374 consecutive new peritoneal
      dialysis patients. The target enrollment is 600 patients. Among these 374
      patients are 217 males (58%), 71 patients age > 70 (19%), 106 with diabetic renal
      disease (28%), 95 with a history of cardiovascular disease (25%) and 60 with
      serum albumin values < 30 Gm/L (16%). There are 307 white patients (82%) and 26
      black patients (7%). The 9 month probabilities were: for patient survival, 96%;
      for technique survival, 93%; peritonitis-free survival, 68%; exit site infection
      free survival, 71%. Final statistical analysis will use multivariate techniques
      to evaluate the relationships among baseline prognostic factors, nutritional
      status and clinical outcomes.

PMID- 1361862
TI  - Adequacy of peritoneal dialysis: does kt/v have the same predictive value as in
      HD? A multicenter study.
AB  - Urea kinetics and the use of KT/V has become a useful tool for assessing adequacy
      of small solute removal in HD. Clinical data supporting the benefit of urea
      kinetic analysis in CAPD patients had been lacking. Using the standards of KT/V
      for hemodialysis, many CAPD patients would be underdialyzed but, most studies
      show no significant difference in morbidity or mortality between CAPD and HD
      patients. We studied retrospectively, 102 patients (48 M, 54 F), aged 54.6 +/-
      14.8 (range 14-82), on CAPD 24.4 +/- 23.9 months (0-120) from 6 hospitals.
      Clinical and biochemical parameters, co-morbidity, mortality, and hospital
      admission rate were registered. During the follow-up (1 year), a significant
      decrease of residual renal function (Kr) from 1.74 +/- 1.86 to 1.31 +/- 1.67 (p <
      0.01) was noticed. The KT/V also decreased from 2.00 +/- 0.47 to 1.89 +/- 0.36 (p
      < 0.01) without change in BUN or plasma creatinine levels. The normalized protein
      catabolic rate (NPCR) decreased from 0.98 +/- 0.28 to 0.93 +/- 0.30 (p < 0.05)
      and serum albumin from 3.7 +/- 0.5 to 3.5 +/- 0.6 (p < 0.001). There was a
      positive correlation between NPCR and KT/V (r = 0.44, p < 0.05) and between NPCR
      with serum BUN (r = 0.27, p < 0.05). There was no correlation between KT/V and
      NPCR neither with hospitalization rate nor clinical symptoms index. The latter,
      however, showed a positive correlation with the co-morbidity index.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1361863
TI  - The place for automated peritoneal dialysis.
AB  - The progress of automated peritoneal dialysis is initmately linked to the
      evolution of automated peritoneal delivery systems. The state of the art devices
      have incorporated computerized programs capable of delivering precise timing and
      volumes of dialysate and have made possible the delivery of CCPD, NPD, IPD or TPD
      with either time-controlled or volume-controlled delivery modes. Data storage and
      telephone transmission to the center have also helped in assessing compliance and
      documentation of dialysis delivered. The most common indications for automated
      peritoneal dialysis remain patient preference and the need for partner
      assistance. However, new indications have emerged from our better understanding
      of peritoneal dialysis kinetics and the recent emphasis on dialysis prescription
      and quality assurance.

PMID- 1361864
TI  - LFA-1 and ICAM-1 molecule expression in jejunal mucosa from children with
      autoimmune enteropathy.
AB  - The expression of adhesion molecules by cells of the small intestinal mucosa was
      compared in gut biopsies from children with autoimmune small intestinal
      enteropathy and normal controls and related to HLA-DR expression by the same
      tissue. Jejunal biopsies were stained by IFL with monoclonal antibodies to LFA-1
      (TS1/22 and CD11a/25.3.1) and ICAM-1 (RR1/1 and 84H10) molecules. LFA-1 and ICAM
      1 positive cells were observed in the lamina propria in all cases and the counts
      were increased in autoimmune enteropathy compared with controls. In addition, in
      4 of 7 cases of autoimmune enteropathy crypt enterocytes were positives for ICAM
      1 when stained with RR1/1 and 3 of the 4 were also positive for LFA-1 when
      stained with both LFA-1 reagents. We speculate on the role of adhesion molecule
      expression in autoimmune enteropathy.

PMID- 1361865
TI  - Analysis of heart rate variability to assess hemodynamic alterations following
      induction of anesthesia.
AB  - Extensive changes in hemodynamics and cardiac rhythm during induction of
      anesthesia may be mediated by altered responses of the autonomic nervous system
      to anesthetic agents. Analysis of the power spectrum of the heart rate (PSHR)
      variability can supply information about the autonomic nervous system, and may be
      used in order to assess this phenomenon. In this study, 78 patients undergoing
      coronary artery bypass graft surgery were evaluated. Anesthesia was induced with
      sufentanil, and neuromuscular blockade with vecuronium, a combination that may
      cause a decrease in heart rate. Before and after induction of anesthesia, the
      heart rate (HR), blood pressure (BP), cardiac output (CO), cardiac index (CI),
      and PSHR components were recorded. PSHR was obtained by using a special algorithm
      and data acquisition system for real-time spectral analysis. A low-frequency
      component (LFa, mainly sympathetic) was analyzed from a band of 0.04 Hz to 0.1
      Hz. A high-frequency component (RFa, parasympathetic) was identified by the
      respiratory frequency spectrum. Alterations of the heart rate after induction of
      anesthesia were defined in order to separate the patient population into two
      groups: slow heart rate (slow-HR) and stable heart rate (stable-HR). Slow heart
      rate was defined as a decrease in HR of more than 20% of the baseline value. The
      variables were analyzed and compared between the slow-HR (n = 25) and stable-HR
      (n = 53) groups in order to verify the possibility of identifying patients prone
      to hemodynamic changes after anesthesia induction. There were no differences in
      preoperative HR, BP, CO, or CI between groups before anesthesia
      induction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361866
TI  - Bradycardia following induction with alfentanil and vecuronium.

PMID- 1361867
TI  - Differential diagnosis of HTLV-I-associated myelopathy and multiple sclerosis in
      Iranian patients.
AB  - Two Iranian patients with chronic progressive spastic paraparesis and urinary
      dysfunction were referred to our hospital with the presumptive diagnosis of
      multiple sclerosis (MS). Routine CSF analysis and magnetic resonance imaging of
      the two patients were only partially characteristic of MS. Testing for antibodies
      to human T-cell leukemia virus type I [HTLV-I] in serum using a radioimmune
      precipitation assay revealed antibodies to HTLV-I in both patients. The infection
      with HTLV-I was confirmed by polymerase chain reaction (PCR) and liquid
      hybridization analysis using primers to the tax/rex region and a corresponding
      probe, demonstrating proviral DNA in peripheral blood mononuclear cells of both
      patients. On the basis of these findings demonstrating the presence of proviral
      HTLV-I DNA in the two Iranian patients, the initial diagnosis of MS was corrected
      to that of HTLV-I-associated myelopathy (HAM). In contrast, several patients with
      definite MS (nine from Germany, two from Iran) with a relapsing and remitting
      form of the disease were tested for HTLV-I infection by enzyme-linked
      immunosorbent assay and PCR, which yielded negative results. However, the mother
      of one HAM patient was found to be infected with HTLV-I. To support an
      association between HTLV-I infection and CNS disease in the two HAM patients, we
      analyzed the production of specific IgG antibodies within the CNS based on a
      simple enzyme immunoassay for viral IgG antibodies in CSF and serum. In the two
      HAM patients there was significant intrathecal antibody production directed
      against HTLV-I, but this was not found in any of the samples from MS
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361869
TI  - Occupancy-response relationships for beta- and alpha 2-adrenergic receptors
      exerting opposing effects on cAMP production.
AB  - In primary glial cultures, norepinephrine (NE) activates both beta-adrenergic
      receptors to increase cAMP formation and alpha 2-adrenergic receptors to
      partially inhibit this response. We used selective alkylating agents to compare
      the concentration-dependence and receptor reserves for activation of each
      subtype. Partial inactivation of beta-receptors with alkylating pindolol (BIM)
      caused a slight decrease in the potency of isoproterenol (ISO) in increasing cAMP
      accumulation and a progressive decrease in maximum response. The KA for ISO was
      9.8 +/- 2 nM, with a 2-3-fold beta-receptor reserve. BIM pretreatment decreased
      the maximal response to NE without significantly altering its apparent EC50 (41
      +/- 6.7 nM). Partial inactivation of alpha 2-adrenergic receptors with EEDQ
      increased the maximal response to NE without significantly altering its apparent
      EC50 (41 +/- 6.2 nM). NE inhibited the cAMP response to ISO with an apparent EC50
      of 38 +/- 1.2 nM. EEDQ pretreatment reduced inhibition of the ISO response by
      both NE and the alpha 2-agonist UK 14,304, and inhibition of the forskolin
      response by UK 14,304. EEDQ pretreatment caused only a small decrease in potency
      for the alpha 2-agonists. The KA for NE in inhibiting the ISO response was 120 +/
      30 nM, indicating a 2-3-fold alpha 2-receptor reserve. These results suggest
      that NE has similar affinities and receptor reserves for beta- and alpha 2
      adrenergic receptors in this system, and activates and inhibits adenylate cyclase
      at the same agonist concentrations.

PMID- 1361868
TI  - Balanced efficiencies of splicing and cleavage-polyadenylation are required for
      mu-s and mu-m mRNA regulation.
AB  - The relative abundance of the RNAs encoding the membrane (mu-m) and secreted (mu
      s) forms of immunoglobulin mu heavy chain is regulated during B cell maturation
      by a change in the mode of RNA processing. This regulation depends on a
      competition between two mutually exclusive RNA processing reactions, cleavage
      polyadenylation at the microseconds poly(A) site and splicing of the Cmu4 and M1
      exons. Previously, the efficiencies of these two reactions were altered
      independently. When an efficient processing signal replaced the normal suboptimal
      signals of the mu gene, a single RNA product was produced exclusively. In this
      report, two efficient signals are combined in a single mu transcript and shown to
      restore a processing balance such that two mRNAs can once again be alternatively
      processed from a single RNA precursor. The ratio of the two RNAs generated from
      these mu genes containing balanced competing strong splice and cleavage
      polyadenylation reactions display the expected developmental shift when expressed
      in B cells and plasma cells. Therefore, the balance between cleavage
      polyadenylation and splicing efficiencies is critical to the developmentally
      regulated expression of mu-s and mu-m mRNA. Also shown here is that the entire mu
      m region, including the M1 and M2 exons and the mu-m poly(A) site, can be
      replaced with SV40 splice and poly(A) sequences. Regulation is maintained in
      these mu genes, indicating that no specific sequences within the mu-m region are
      required.

PMID- 1361870
TI  - Human alpha-calcitonin gene-related peptide stimulates adenylate cyclase and
      guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide.
AB  - 1. The signal transduction pathway for vasorelaxation induced by human alpha
      calcitonin gene-related peptide (human alpha-CGRP) was studied in rat thoracic
      aortic rings preconstricted with noradrenaline (10(-7) M). 2. Vasorelaxation by
      human alpha-CGRP was inhibited by haemoglobin (10(-6) M) and methylene blue (10(
      5) M) but was unaffected by ibuprofen (10(-5) M). 3. Acetylcholine caused a 16
      fold increase in levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP) with
      levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) being unaltered.
      Human alpha-CGRP caused a 12 fold increase in levels of cyclic GMP but, in
      contrast to acetylcholine, evoked a 2.5 fold rise in levels of cyclic AMP. The
      rises in cyclic nucleotides evoked by human alpha-CGRP and acetylcholine were
      dependent on the presence of an intact endothelium. 4. NG-nitro-L-arginine (L
      NOARG: 10(-5) M), which inhibits nitric oxide synthetase, inhibited the relaxant
      response to human alpha-CGRP and cyclic GMP accumulation without affecting the
      cyclic AMP accumulation. 5. The data presented in this paper suggests that human
      alpha-CGRP relaxes the rat thoracic aorta by releasing nitric oxide and
      stimulating guanylate cyclase. The stimulation of adenylate cyclase by human
      alpha-CGRP probably precedes the activation of nitric oxide synthase but could be
      unrelated to the relaxant response.

PMID- 1361872
TI  - Multiple sigma binding sites in guinea-pig and rat brain membranes: G-protein
      interactions.
AB  - 1. Evidence is accumulating for multiple sigma (sigma) sites in the mammalian
      CNS. 2. We have addressed this problem and have examined sigma site - G-protein
      coupling in guinea-pig and rat brain membranes. 3. Ditolylorthoguanidine (DTG),
      (+)-3-(3-hydroxyphenyl)-N-1-(propyl)piperidine (3PPP) and dextromethorphan
      displaced [3H]-DTG (3.4 nM) with low Hill slopes of 0.5, 0.6 and 0.6,
      respectively in guinea-pig brain membranes. 4. In the presence of 5'
      guanylylimidodiphosphate (Gpp(NH)p; 100 microM), the specific binding of [3H]-DTG
      was reduced by 36.7%, the Hill slope of 3PPP was increased to near unity, the
      ability of dextromethorphan to displace DTG was virtually abolished and the Hill
      slope for DTG remained low (0.7), indicating the presence of at least two binding
      sites. These data indicate that although Gpp(NH)p removes a dextromethorphan high
      affinity site, two DTG selective sites remain in the presence of Gpp(NH)p. 5. The
      present study suggests that DTG binds to at least three sites in guinea-pig brain
      membranes, at least one of which is G-protein linked. 6. In rat brain membranes,
      DTG displaced itself (3.4 nM) with a Hill slope near 1. 3PPP displacement of [3H]
      DTG was comparable with the guinea-pig (Hill slope 0.5) and displaced from more
      than 1 site. Dextromethorphan did not displace [3H]-DTG at concentrations below
      10 microM. 7. The heterogeneity of sigma sites appears to be less in rat than in
      guinea-pig brain membranes.

PMID- 1361871
TI  - Identification of alpha 1-adrenoceptor subtypes in the rat vas deferens: binding
      and functional studies.
AB  - 1. The alpha 1-adrenoceptor subtypes of the prostatic and epididymal portion of
      rat vas deferens were characterized in binding and functional experiments. 2. In
      saturation experiments, [3H]-prazosin bound to two distinct affinity sites in the
      epididymal portion of rat vas deferens (pKD = 10.1 +/- 0.13 and 9.01 +/- 0.15,
      Bmax = 507 and 1231 fmol mg-1 protein, respectively). In the prostatic portion
      [3H]-prazosin bound to a single affinity site (pKD = 9.82 +/- 0.04, Bmax = 924
      fmol mg-1 protein). 3. In the displacement experiments, unlabelled prazosin
      displaced biphasically the binding of 200 pM [3H]-prazosin to the epididymal
      portion; the resulting two pKI values were consistent with the affinity constants
      obtained in the saturation experiments. WB4101 (2-(2,6-dimethoxy-phenoxyethyl)
      amino-methyl-1,4-benzodioxane) and benoxathian also discriminated the two
      affinity sites in the epididymal portion and the population of low affinity sites
      for the three antagonists was approximately 40%. On the other hand, the prostatic
      portion predominantly showed a single affinity site for prazosin, WB4101 and
      benoxathian, although the presence of a small proportion (less than 10%) of the
      low affinity site could be detected. HV723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3
      ((2-(2-methoxyphenoxy)ethyl)-a min o)- propyl) benzeneacetonitrile fumarate)
      displaced the [3H]-prazosin binding monophasically with a low affinity in both
      halves. 4. Pretreatment with chlorethylclonidine (CEC) at concentrations higher
      than 1 microM inhibited 700 pM [3H]-prazosin binding to the prostatic portion by
      approximately 50%. However, the inhibition in the epididymal portion was much
      less (approximately 21% at 50 microM CEC).5. In the functional study, the
      contractile response to noradrenaline was competitively inhibited by prazosin,
      WB4101, benoxathian and HV723 with similar and low affinities (pKB value ranging
      from 8.0to 9.0) in the epididymal portion of rat vas deferens. In the prostatic
      portion of rat vas deferens,noradrenaline also produced a contraction, but the
      maximal amplitude of contraction developed was approximately one-fourth of that
      in the epididymal portion. Prazosin and WB4101 also inhibited the contractile
      response of the prostatic portion with the pKB values similar to those obtained
      in the epididymal portion. The contractions to noradrenaline in both portions
      were potently attenuated by 1 LM nifedipine but were not affected by pretreatment
      with 1O LM CEC.6. Under conditions where P2x-purinoceptors and prejunctional M2
      adrenoceptors were blocked, electrical transmural stimulation produced a rapidly
      developing phasic contraction and a subsequent tonic contraction in the
      epididymal portion of rat vas deferens. The phasic and tonic contractions were
      inhibited in a concentration-dependent manner by prazosin (ICs = 25.7 and 25.9
      nm, respectively),WB4101 (ICo= 7.27 and 7.58 nM), benoxathian (ICs = 10.9 and
      8.66 nM) and HV723 (ICs = 15.9 and 14.9 nM). Nifedipine selectively attenuated
      the tonic contraction induced by electrical stimulation, and the residual phasic
      response was inhibited by the antagonists mentioned above with similar affinities
      to those in the absence of nifedipine. CEC (10 gM) had little effect on the
      adrenergic neurogenic contractions.7. The present results indicate the presence
      of two distinct alpha&-adrenoceptor subtypes in the rat vas deferens, which show
      respectively high and low affinities for each of prazosin, WB4101 and
      benoxathian,and presumably correspond to putative MIA and alL subtypes according
      to the recent am-adrenoceptorsubclassifications. The contractions induced by
      exogenous and endogenous noradrenaline seem to be predominantly mediated through
      the alL subtype. The heterogeneous distribution of the low affinity sites(alL
      subtype) may well explain differences in functional responsiveness between the
      two portions of rat vas deferens.

PMID- 1361873
TI  - Muscarinic blockade of beta-adrenoceptor-stimulated adenylyl cyclase: the role of
      stimulatory and inhibitory guanine-nucleotide binding regulatory proteins (Gs and
      Gi).
AB  - 1. The functional antagonism that exists between muscarinic and beta-adrenoceptor
      function in guinea-pig tracheal smooth muscle was investigated by assessing Gs
      and Gi regulated adenylyl cyclase activity in isolated membranes. 2. Membranes
      from guinea-pig tracheal smooth muscle contain both Gi alpha and Gs alpha as
      assessed by Western blots with anti-G-protein antibodies. 3. GppNHp, a non
      hydrolysable analogue of guanosine 5'-triphosphate (GTP), was shown to stimulate
      adenylyl cyclase activity at high concentrations (10(-6)-10(-4) M). GppNHp also
      produced a concentration-dependent reduction in pertussis toxin-catalysed
      adenosine diphosphate (ADP)-ribosylation of Gi alpha. 4. Pretreatment of tracheal
      smooth muscle slices with methacholine (10(-6) M) provoked a blockade of
      isoprenaline plus GTP, GppNHp- and GTP-stimulated adenylyl cyclase. 5. Addition
      of methacholine to membranes did not trigger inhibition of GTP-stimulated
      adenylyl cyclase activity but did block the isoprenaline-mediated augmentation of
      GTP-stimulated adenylyl cyclase activity. 6. Pretreatment of tracheal smooth
      muscle with methacholine (10(-6) M) provoked a blockade of cholera toxin
      catalysed NAD(+)-dependent ADP-ribosylation of Gs alpha. 7. Phorbol-12-myristate
      13-acetate (PMA)-treatment of tracheal smooth muscle slices actually enhanced
      GppNHp-stimulated adenylyl cyclase activity in subsequently prepared membranes.
      8. We suggest that methacholine in addition to inhibiting adenylyl cyclase via a
      Gi-dependent mechanism induces a functional inactivation of Gs activity. These
      results together may explain the functional antagonism that exists between
      increased muscarinic tone and the ability of beta-adrenoceptor agonists to
      provoke excitation-contraction uncoupling.

PMID- 1361874
TI  - The glutamate antagonist, MK-801, does not prevent dopaminergic cell death
      induced by the 1-methyl-4-phenylpyridinium ion (MPP+) in rat dissociated
      mesencephalic cultures.
AB  - The neuroprotective effects of MK-801, a non-competitive antagonist of the N
      methyl-D-aspartate (NMDA) receptor/channel, were assessed in a culture model
      which reproduces in vitro the selective degeneration of mesencephalic
      dopaminergic neurons seen in parkinsonian brains. Dissociated mesencephalic cells
      derived from rat embryonic brains were subjected for 24 h to intoxication by the
      1-methyl-4-phenylpyridinium (MPP+), the active metabolite of the 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPP+ at 3 and 10 microM produced
      selective and dose-dependent damages to dopaminergic neurons as quantified by the
      loss of the number of TH immunoreactive cells and the loss of [3H]DA uptake
      whereas other cell types remained unaffected. MK-801 at 3 and 10 microM failed to
      rescue degenerating dopaminergic neurons in presence of MPP+. At 50 microM, i.e.
      the highest concentration that is not toxic by itself in this culture system, MK
      801 was also found ineffective. Furthermore, degree of dopaminergic cell damage
      was not reduced when repeated additions of the glutamate antagonist (10 microM/6
      h for 24 h) were performed during exposure to MPP+ or when mesencephalic cultures
      were left after intoxication for up to 2 days in a culture medium still
      supplemented with MK-801 but free of toxin. In accordance with these results, MK
      801 did not affect significantly the uptake of [3H]DA in control cultures,
      thereby suggesting that this compound cannot prevent intracellular accumulation
      of MPP+ within dopaminergic neurons. At higher concentrations of MPP+ (100
      microM) tested, toxic effects were seen toward dopaminergic neurons and non
      dopaminergic cells as quantified by Trypan blue dye accumulation and loss of
      [3H]GABA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361875
TI  - Somatostatin release in rat neocortex during gamma-hydroxybutyrate-provoked
      seizures: microdialysis combined with EEG recording.
AB  - Gamma-hydroxybutyrate (GHB) was intracortically applied in two doses (first 10
      and then 20 mg/ml) to awake Wistar rats using microdialysis. Simultaneously, EEG
      and the release of somatostatin-like immunoreactivity (SLI) were measured from
      the frontal cortex. Intracerebrally administered GHB induced cortical
      epileptogenic spikes, but not high voltage spindles (HVS) as reported after
      systemic administration, and seizures with myoclonic jerks and contraversive head
      movements. Compared to the basal level, GHB (10 mg/ml) initially increased the
      release of SLI (p < 0.05). However, when the frequency of spikes and seizures
      rose rapidly (p < 0.001), SLI release decreased significantly (p < 0.001).
      Minimum release of SLI occurred when seizures were most frequent (during
      perfusion with 20 mg/ml GHB), while after removal of the drug it rose above the
      basal level (p < 0.05). According to these results, intracortically applied GHB
      increases the release of SLI in the surrounding tissue. However, further exposure
      of GHB leads to a manifestation of epileptic spikes and seizures, during which
      the release of SLI is significantly attenuated. This suggests that release of
      somatostatin is affected during epileptic phenomena induced also by intracortical
      GHB application.

PMID- 1361876
TI  - Hippocampal long-term potentiation in nucleus basalis magnocellularis-lesioned
      rats.
AB  - The probability of hippocampal long-term potentiation induction in the mossy
      fiber CA3 and commissural/associational CA3 responses and the cortical levels of
      choline acetyltransferase (ChAT) activity were compared in right nucleus basalis
      magnocellularis (NBM)-lesioned rats. A 50% reduction in the right cortical ChAT
      activity was demonstrated 4 weeks after an ibotenic acid lesion of the NBM. No
      significative differences were found in the probability of LTP induction of right
      hippocampal slices in sham-operated rats from 10 to 40 days after the injection
      into the right NBM. On the contrary, a progressive and significative increase in
      the probability of LTP induction was shown in right hippocampal slices of NBM
      lesioned rats from 10 to 40 days after the injection of ibotenic acid into the
      right NBM. The results demonstrated the appearance of a paradoxical increase of
      hippocampal synaptic plasticity when the cortical cholinergic biochemical
      alterations are still present. This finding might be responsible for a
      behavioural recovery, in NBM-lesioned rats.

PMID- 1361877
TI  - Somatostatin and growth hormone-releasing factor release from Zucker rat
      hypothalamic tissue.
AB  - Plasma somatotropin (ST) levels are depressed in the genetically obese Zucker rat
      compared to those of their littermates. It is believed that this defect is
      associated with one or both of the hypothalamic neuropeptides that control ST
      release: growth hormone releasing factor (GRF) and somatostatin (SS). The
      mechanism by which SS and GRF neuropeptides are regulated remains uncertain. The
      objective of this study was to examine the effect of 2 deoxy-glucose (2DG),
      isoproterenol (ISO), tryptophan (TRP), and 5HT on SS and GRF release in
      hypothalamic tissue from lean and obese Zucker rats. An in vitro perifusion
      system was established to examine the release of SS and GRF from perifused
      hypothalami taken from 8- and 12-week-old Zucker rats under basal conditions and
      in response to 2DG, ISO, TRP, 5HT, and KCl administration. Hypothalami were
      perifused with Dulbecco's modified eagle's medium continuously at 37 degrees C
      for 5 h at a flow rate of 100 ml/min. ISO and 2DG significantly (p < 0.05)
      increased SS levels from the obese rat, but no effect was observed from the lean
      littermate. GRF was not affected by 2DG or ISO in either genotypes. TRP and 5HT
      failed to affect SS or GRF release in lean or obese Zucker rats. It is proposed
      that the obese Zucker rat is more sensitive to glucose deprivation and to beta
      adrenergic stimulation of SS release than the lean littermate.

PMID- 1361879
TI  - Benzodiazepines and acute psychotic agitation.

PMID- 1361878
TI  - Benzodiazepine receptor binding of nonbenzodiazepines in vivo: alpidem, zolpidem
      and zopiclone.
AB  - Several classes of nonbenzodiazepine compounds, including imidazopyridines such
      as alpidem and zolpidem and cyclopyrrolones, e.g., zopiclone, have effects
      similar to benzodiazepines and may act at the benzodiazepine receptor in brain.
      We characterized the binding of these compounds to the benzodiazepine site in
      three brain regions using specific uptake of the high-affinity ligand [3H]Ro15
      1788 (flumazenil). For alpidem, benzodiazepine binding was decreased in cortex
      and hippocampus with increasing drug dose. For zolpidem, receptor binding was
      reduced in cortex without a dose-response effect and no effect was observed on
      cerebellar binding. Zopiclone did not alter binding except for a decrease in
      binding at the lowest dose evaluated and an increase in binding above control at
      the highest dose. These data corroborate prior studies indicating that the
      imidazopyridines appear to act at the benzodiazepine receptor, but do not support
      receptor subtype selectivity of zolpidem. The limited effect of zopiclone except
      for increased binding at high doses is also consistent with prior studies
      suggesting that zopiclone acts at a site distinct from the benzodiazepine
      receptor.

PMID- 1361880
TI  - Complement 4 gene deletion in patients with IgA nephropathy and Henoch-Schonlein
      nephritis.
AB  - The fourth component of complement (C4), especially B isotype, has been said to
      be deficient in the IgA nephropathy and Henoch-Schonlein nephritis. However, the
      association between these diseases and C4 deficiency was questioned recently, and
      the usual C4 allotyping method is unable to discriminate the C4 deficiency from
      the C4 duplication. So by combining the DNA restriction fragment length
      polymorphism with the usual C4 allotyping, we tried to determine whether the
      deficiency of C4 can be demonstrated in the DNA level. We found that the
      frequency of C4 gene deletion was increased, although the frequency of null
      phenotype was not different from the control. From these results we can say that
      C4 gene deletion is a genetic risk factor in these diseases, at least in the
      Japanese population.

PMID- 1361881
TI  - Tumor-specific chemoimmunotherapy of murine fibrosarcoma using tumor-specific
      transplantation antigen, cyclophosphamide, and interleukin-2.
AB  - The anti-tumor effect of active specific chemoimmunotherapy, using butanol
      extracted tumor-specific transplantation antigen (TSTA), cyclophosphamide (CY),
      and continuous intrasplenic infusion of interleukin-2 (IS-IL-2), was assessed in
      a C3H/HeJ murine methylcholanthrene (MCA)-induced fibrosarcoma model. Sole
      administration of TSTA induced tumor-specific, suppressor T cells in the spleens
      of mice bearing 3-day established tumors. Concomitant low-dose (20 mg/kg) CY
      treatment not only inhibited TSTA-mediated suppressor cell induction, but also
      evoked splenic lymphocytes of tumor-bearing mice to display tumor-specific
      cytotoxic activity. High-dose (200 mg/kg) CY abrogated the immunotherapeutic
      benefit. The immune effectors generated by TSTA plus CY bear the Thy 1, L3T4, Lyt
      2 phenotype. Continuous IS-IL-2 infusion in combination with TSTA and CY induced
      tumor-specific Lyt 2+ cytolytic T cells, as well as the activation of L3T4+
      cytostatic T cells. Thus, a triple regimen using TSTA, CY, and IS-IL-2 appears to
      augment CTL induction in tumor-bearing hosts undergoing stimulation of helper
      elements by TSTA and inhibition of suppressor cells by CY.

PMID- 1361882
TI  - Ethinyl estradiol-induced cell proliferation in rat liver. Involvement of
      specific populations of hepatocytes.
AB  - Hepatocyte proliferation was analyzed in vivo during the time course of
      continuous administration to rats of the liver tumor promoter ethinyl estradiol
      (EE) at 10 p.p.m. in the diet. EE-induced acute liver hyperplasia was detected in
      male and female Sprague-Dawley rats as an increased mitotic index of hepatocytes
      after 2 days of treatment. 5'-Bromodeoxyuridine (BrdU) labeling showed that
      proliferating hepatocytes were randomly distributed throughout the hepatic
      lobule. Subsequently, and still during the first few days of continuous EE
      treatment, hepatocyte proliferation decreased to control levels, and a transient
      increase in the incidence of apoptosis in the liver was detected. Although
      consistent with the concept of liver growth regression after mitogen-induced
      hyperplasia, these results differ from others reported to date in that, in our
      experiments, the cessation of cell proliferation and the subsequent growth
      regression occurred without withdrawal of EE in our experiments. After returning
      to control levels, hepatocellular proliferation again increased between 3 and 6
      months of chronic treatment and remained activated during the following months of
      continuous treatment, as seen by accumulative BrdU labeling. Proliferating
      hepatocytes were predominantly located in zone 2 of the hepatic lobule at this
      time, surrounding a periportal zone of vacuolated hepatocytes, which were also
      induced by the treatment. Moreover, hyperplasia of basophilic hepatocytes was
      also seen around some portal spaces. In another set of experiments, chronic EE
      induced activation was characterized by flow cytometry on hepatocytes isolated
      from male Fischer rats. Ploidy analysis of hepatocyte cell suspensions showed
      that the normal polyploid pattern of hepatocytes was altered by EE, the
      proportion of diploid hepatocytes rising considerably. The results also showed
      that these diploid cells were the most susceptible hepatocyte population to EE
      induced proliferation, as shown by a combination of BrdU labeling and cell
      sorting methods. In contrast to Sprague-Dawley rats, no vacuolated cells were
      found histologically in the livers of these animals and the proliferating
      hepatocytes were located adjacent to the portal areas. These results taken
      together support the existence of cell target populations in the liver responding
      to the effects of tumor promoters. The finding that a subpopulation of diploid
      hepatocytes was the liver cell class most susceptible to proliferation during
      chronic EE treatment may explain, at least in part, the behavior of EE as a tumor
      promoter in hepatocarcinogenesis.

PMID- 1361883
TI  - Proto-oncogene activation in liver tumors of hepatocarcinogenesis-resistant
      strains of mice.
AB  - Activation of the ras family of oncogenes occurs frequently in liver tumors of
      the B6C3F1 mouse, a strain which is highly sensitive to hepatocarcinogenesis.
      Many other mouse strains are much more resistant to hepatocarcinogenesis; the aim
      of this study was to determine the frequency and pattern of oncogene activation
      in spontaneous and chemically induced liver tumors of three such strains, the
      C57BL/6J, the C57BL/6 x DBA/2 F1 hybrid (B6D2F1) and the C57BL/6 x Balb/c F1
      hybrid (B6BCF1). The C57BL/6, DBA/2 and Balb/c strains are all relatively
      resistant to spontaneous hepatocarcinogenesis (1.5-3.6% of animals develop liver
      tumors in 2 years); with regard to chemically induced hepatocarcinogenesis the
      Balb/c is highly resistant, the C57BL/6 has low susceptibility and the DBA/2 has
      low to moderate susceptibility. The nude mouse tumorigenicity assay was used to
      search for activated oncogenes in 15 C57BL/6J liver tumors induced by a single
      neonatal dose of vinyl carbamate (VC, 0.15 mumol/g body weight). Three tumors
      contained H-ras genes activated by point mutations at codon 61 and one contained
      a non-ras oncogene. The polymerase chain reaction and allele-specific
      oligonucleotide hybridization were used to study H-ras mutations in spontaneous
      and VC-induced tumors from all three strains of mice. The frequency of H-ras
      codon 61 mutations in tumors induced by 0.15 mumol/g body weight VC in the
      C57BL/6J mouse (5/37) was similar to that in spontaneous tumors (2/9);
      surprisingly, tumors induced by a lower dose of VC (0.03 mumol/g body weight) had
      a higher frequency of H-ras mutations (12/28). The frequencies of H-ras
      activation detected in VC (0.03 mumol/g body weight)-induced tumors from the two
      F1 hybrids studied differed markedly. Only one VC-induced B6BCF1 tumor contained
      a mutated H-ras gene (1/10), whereas the majority of B6D2F1 tumors contained such
      mutations (23/33). Several spontaneous B6D2F1 liver tumors contained H-ras codon
      61 mutations (6/15). Thus, H-ras activation frequency does not determine
      susceptibility to hepatocarcinogenesis in inbred mice and their F1 hybrids, since
      a relatively high frequency of H-ras mutations was observed in two resistant
      strains and a low frequency was found in the other strain.

PMID- 1361884
TI  - Expression of cell adhesion molecules and catecholamine synthesizing enzymes in
      the developing rat adrenal gland.
AB  - Cell adhesion molecules play a major role in determining tissue architecture
      during histogenesis. This immunocytochemical study of the adrenal gland examines
      the embryonic and early postnatal cellular expression of two neural cell adhesion
      molecules, NCAM and L1, which are widely expressed in brain and have been found
      also to be expressed in the adult rat adrenal gland. In parallel, antibodies
      directed against two neuroendocrine cell markers, tyrosine hydroxylase and
      phenylethanolamine N-methyltransferase, were employed to verify the phenotypic
      nature of developing chromaffin cells in order to correlate cell adhesion
      molecule expression with the state of chromaffin cell differentiation. NCAM was
      found to be expressed by chromoblasts within extra-adrenal blastema (i.e. before
      their migration into the cortical primordium) at the 16th day of embryonic life.
      It continued to be expressed by all developing chromaffin cells after their
      infiltration into the developing adrenal gland at all ages. L1 was also expressed
      by chromoblasts in extra-adrenal sites, but was found only in a subpopulation of
      chromaffin cells within the cortical primordium from the 16th embryonic day
      onwards. Those chromoblasts which expressed L1 constituted relatively large
      compact cell clusters within the gland at this stage, while intra-adrenal
      chromaffin cells not expressing L1 were dispersed in small cell groups. L1 was
      also strongly expressed by nerve fibres (and their surrounding Schwann cells)
      which appeared to innervate cell groups as early as the 16th embryonic day. Both
      extra- and intra-adrenal chromoblasts expressed tyrosine hydroxylase, but the
      large L1-positive cell aggregates were less intensely immunoreactive for tyrosine
      hydroxylase than were cells in small groups. PNMT expression was restricted to L1
      negative intra-adrenal chromoblasts present in small groups. Ultrastructural
      observations demonstrated that cells expressing L1 contained few secretory
      granules at the 18th embryonic day. It is concluded from these data that these
      chromoblasts are the precursors of the noradrenergic cells found in the mature
      gland. In addition, the arrangement of noradrenergic chromaffin cells in the form
      of homotypic cell groups throughout the course of histogenesis of the adrenal
      medulla is likely to be a direct consequence of the exclusive co-expression of
      both NCAM and L1 by this subpopulation of maturing chromaffin cells.

PMID- 1361885
TI  - Cellular expression of somatostatin in MAM-induced microencephaly in the rat.
AB  - Methylazoxymethanol acetate (MAM) is a mitotic inhibitor that has been used to
      selectively destroy neuroblasts at specific times during gestation. The
      administration of MAM results in a dose-dependent microencephaly. Following MAM
      treatment at 15 days of gestation, we have noted an increase in the level of SS
      immunoreactivity in the neocortex, as determined by radioimmunoassay. Northern
      blot analysis for preproSS mRNA revealed an increase in MAM-treated cortex. The
      cellular distribution of SS has been determined using in situ hybridization and
      immunocytochemistry. There was a 30% increase in the density of SS-immunoreactive
      neurons in the cortex of the MAM-treated animals. These data suggest that SS
      neurons in the cortex are spared following MAM treatment at GD 15.

PMID- 1361886
TI  - Ultrastructure of spared dopamine terminals in caudate-putamen nuclei of adult
      rats neonatally treated with intranigral 6-hydroxydopamine.
AB  - Residual dopamine terminals in the dorsal striatum, caudate-putamen nuclei (CPN),
      of adult rats neonatally lesioned with 6-hydroxydopamine (6-OHDA) sustain a
      relatively high level of dopamine release. We examined whether there were
      morphological differences in the spared dopamine terminals that might correlate
      with this increased efficacy. Postnatal male rat pups from 50 litters were
      pretreated with desmethylimipramine (DMI) to protect from non-specific monoamine
      damage, then given unilateral intranigral injections of 6-OHDA or vehicle.
      Coronal sections through the CPN and substantia nigra of the surviving adult
      animals from each litter were co-processed for immunoautoradiographic or
      immunoperoxidase localization of the catecholamine synthesizing enzyme, tyrosine
      hydroxylase (TH). Quantitative ultrastructural analysis established that in
      animals showing maximal (greater than 90%) depletions in immunoautoradiographic
      labeling for TH, the number of TH-labeled axons in the CPN ipsilateral to the 6
      OHDA injections was reduced to one third of the number seen in the contralateral,
      unlesioned hemisphere, or the CPN from vehicle-injected animals. The
      ultrastructural features of residual terminals ipsilateral to 6-OHDA lesions were
      morphologically similar to those of the contralateral side or in vehicle-injected
      animals. However, in comparison with controls, these TH-labeled terminals had
      significantly larger mean cross-sectional diameters. When subdivided into groups
      according to size, there were significantly fewer small (0.0-0.1 micron 2) and
      more large (0.41-0.50 micron 2) TH-immunoreactive profiles in lesioned versus
      unlesioned CPN. The remaining TH-labeled terminals ipsilateral to the 6-OHDA
      lesions also appeared to be more often in direct contact with unlabeled soma and
      proximal dendrites as opposed to dendritic spines in the unlesioned CPN. These
      results suggest that the enhanced activity of dopamine neurons innervating the
      CPN after nigral 6-OHDA lesions may contribute to changes in size and target of
      their terminals. Alternatively, the observed large size of remaining dopamine
      terminals may reflect selective vulnerability of smaller axons to 6-OHDA
      toxicity.

PMID- 1361887
TI  - The Diabetic Foot 1992.

PMID- 1361888
TI  - Sodium salt neutral entry at the apical membrane of the gallbladder epithelium:
      comparing different species.

PMID- 1361889
TI  - Sensory and motor innervation of bird intrafusal muscle fibers.
AB  - 1. Most bird muscle spindles are supplied by only one primary afferent. 2.
      Secondary afferents occur irregularly. 3. Sensory terminals are covered by a
      basal lamina and a collagenous sheath. 4. Two types of motor terminal are
      recognized which can be referred to specific types of intrafusal fiber. 5. The
      sensory and motor innervation of bird intrafusal fibers is less understood than
      that of mammalian intrafusal fibers.

PMID- 1361890
TI  - Retinoids and the molecular basis of limb patterning.

PMID- 1361891
TI  - Effects of propionate on the acid microclimate of hen (Gallus domesticus) colonic
      mucosa.
AB  - 1. Short-chain fatty acid absorption in hen colon is protonated across the apical
      border coupled to an apical electrogenic proton pump. 2. The surface pH of the
      isolated colonic epithelium was 6.27 +/- 0.05, when incubated in Krebs-phosphate
      buffer pH 7.0. 3. Propionate 7 and 40 mmol/l in the incubation medium (pH 7.0)
      increased microclimate pH to 6.47 +/- 0.04 and 6.56 +/- 0.04. Inhibition of
      metabolic activity by potassium cyanide 1 mmol/l increased surface pH to 6.66 +/-
      0.06. 4. The calculated concentration of propionic acid in the microclimate is
      near-linearly related to the propionate concentration. Thus, the acid
      microclimate is not responsible for the Michaelis-Menten like kinetics of
      propionate transport.

PMID- 1361892
TI  - Lipid reserves and body composition in postreproductive anurans.
AB  - 1. The mass of lipid extracted from 13 species of adult anurans collected
      immediately after reproduction differed between sexes. 2. Covariance analyses of
      lipid mass with body mass as the covariate indicated that females had
      significantly more lipid than males; the proportion of lipid as a percentage of
      body mass was correlated significantly with water content of males, but was not
      correlated significantly in females. 3. Heat of combustion of extracted lipid
      increased among species in relation to the timing of reproduction; species that
      bred later in the year had a greater energy content per gram of lipid. 4. Major
      changes in composition during growth and metamorphosis of bullfrogs (Rana
      catesbeiana), include increases in lipid and energy content per gram of tissue
      interrupted by a severe decline of lipid reserve during metamorphosis.

PMID- 1361893
TI  - Tetanus responses under rapid bath solution change: electrotonic depolarization
      of transverse tubules may release Ca2+ from sarcoplasmic reticulum of Rana
      japonica skeletal muscle.
AB  - 1. Single skeletal muscle fibers were transferred from a normal Ringer solution
      to Na+ ion free solution, and vice versa, and tetanus responses were recorded
      immediately after the transfer. 2. Fractional tetanus tension recorded
      immediately after the displacement from the Na+ ion free solution to normal
      Ringer solution was dependent on fiber diameter. 3. Diffusion of Na+ ions along
      the transverse tubules was simulated [apparent diffusion constant was 3.11 x 10(
      6) (cm2/s)]. 4. Our results suggest that the electronic spreading of membrane
      potential, caused by an action potential in the transverse tubules, could release
      Ca2+ ions from sarcoplasmic reticulum.

PMID- 1361894
TI  - Epidermal growth factor alters the electrolyte profile of lactating ewes (Ovis
      aries).
AB  - 1. Lactating ewes were treated with mouse epidermal growth factor (EGF) at a dose
      rate of 0.5 mg/day for 4 days and its effects on the electrolyte profile were
      observed. 2. There was no effect of EGF on plasma concentrations of sodium or
      potassium, although urinary and total (in urine and milk) losses of both were
      reduced. 3. EGF-induced hypocalcaemia was associated with reduced milk calcium
      secretion and increased urinary calcium excretion whereas EGF-induced
      hypermagnesaemia was associated with reduced urinary and total magnesium losses.
      4. Glomerular filtration rate was reduced during EGF infusion. 5. Chronic
      intravenous EGF infusion affects the electrolyte profile by altering electrolyte
      secretion by the mammary gland and renal electrolyte excretion.

PMID- 1361895
TI  - Physiological responses to exercise and hypoglycaemia stress in pigs of differing
      adrenal responsiveness.
AB  - 1. Twelve Large White x Landrace male pigs, six with high adrenocortical response
      to ACTH, and six with low response, were subjected to mild and moderate exercise,
      and then to insulin-induced hypoglycaemia. 2. Plasma ACTH, cortisol,
      catecholamines and some haematological and plasma biochemical parameters were
      determined in response to exercise, and glucose and cortisol in response to
      insulin challenge. 3. High responders had significantly greater increases than
      low responders in ACTH, cortisol and catecholamines following exercise, and in
      cortisol following insulin challenge. 4. The results suggest that differences in
      adrenocortical response to exogenous ACTH are an accurate reflection of the
      animal's response to stressful stimuli.

PMID- 1361896
TI  - Factors affecting oxygen consumption in wild-caught yellow-bellied marmots
      (Marmota flaviventris).
AB  - 1. All age groups gained mass during the active season, but mass-gain of adult
      females was delayed during lactation. 2. The relationship of body mass to
      metabolic rate varied widely; when the relationship was significant, R2 varied
      from 10.3 to 72.6%. Body mass affects VO2 more during lactation than at any other
      period. 3. Mean VO2 of adult males was higher in June than that of adult, non
      lactating females. 4. VO2 of reproductive females was significantly higher during
      lactation than during gestation or postlactation because specific VO2 varied.
      Specific VO2 of non-reproductive females declined over the active season. 5.
      Specific VO2 of all age groups declined between the premolt and postmolt periods.
      The reduced maintenance costs can contribute 20-46% to daily growth. 6. Observed
      VO2 was lower than the value predicted from intraspecific or interspecific Bm:M
      regressions. 7. VO2 of wild-caught marmots was lower than that of marmots
      maintained in the laboratory, probably because of dietary differences. 8. Because
      basal metabolism is a stage on a food-deprivation curve, we suggest that basal
      metabolic rate is not an appropriate measure of the metabolic activity of free
      ranging animals.

PMID- 1361898
TI  - A relationship between circulating natural glucocorticoids and the mechanical
      responses of the heart in atricial and precocial rodents.
AB  - 1. A comparison was made of the mechanical performance of heart muscle from
      mouse, an atricial mammal, with corticosterone as glucocorticoid and spiny mouse
      (Acomys cahirinus), a precocial mammal, with cortisol as glucocorticoid. 2. Force
      frequency responses were negative in mouse and positive in spiny mouse. 3. During
      recovery, there was a gradual increase and an overshoot in the mouse, while in
      the spiny mouse there was an initial enhanced response, diminishing gradually
      with time. 4. High calcium concentration inhibited contractile tension in mouse
      heart, while it was positively inotropic in spiny mouse heart. Changes in the
      concentration of calcium did not change the patterns of force-frequency response.
      5. Lowering the experimental temperature increased the time course and amplitude
      of the tension curve. However, various parameters exhibited different temperature
      sensitivity. 6. There was a significant difference in the levels of circulating
      cortisol between male and female spiny mice. 7. It is proposed that the
      differences in the mechanical responses of mouse and spiny mouse hearts may be
      explained in terms of the effects of the specific glucocorticoid hormone on the
      development of the sodium-calcium exchanger.

PMID- 1361899
TI  - The changes in body temperature, oxygen consumption, CO2 production and muscle
      protein turnover rate by selection for body size in Japanese quail, Coturnix
      coturnix japonica.
AB  - 1. Body temperature, oxygen consumption, CO2 production and muscle protein
      degradation rate were measured in the three quail lines selected for body size, a
      random bred line (RR) and two lines selected for large (LL) or small (SS) body
      size. 2. The body temperature at 15 weeks of age was highest for small body size
      line and lowest for large body size line. 3. The body temperature, oxygen
      consumption and CO2 production of females were significantly higher than that of
      males. 4. The fractional degradation rate of muscle protein of SS, RR and LL
      lines were measured as 2.4, 1.6 and 1.2% per day in male, and 2.6, 1.7 and 1.4%
      per day in female.

PMID- 1361900
TI  - Fibre digestion and digesta retention time in guinea-pigs (Cavia porcellus),
      degus (Octodon degus) and leaf-eared mice (Phyllotis darwini).
AB  - 1. Digestibilities of feed and turnover time (1/k), Transit time (TT) and mean
      retention time (MRT: 1/k + TT) of fluid and particle markers were measured in the
      guinea-pig (Cavia porcellus), degu (Octodon degus) and leaf-eared mouse
      (Phyllotis darwini) fed a diet containing 50% alfalfa. 2. The digestibility of
      fibre and the retention time of digesta were highest in the guinea-pig followed
      by the degu and lowest in the leaf-eared mouse. 3. The difference in the
      retention time of digesta, resulting from the variation in the digestibility of
      fibre, between the three animals can be considered to be related to their body
      mass.

PMID- 1361897
TI  - Specificity of the permissive effect of D-glucose on insulin release in chicken
      pancreas.
AB  - 1. As previously shown, 14 mM D-glucose, a non-insulinotropic concentration in
      isolated chicken pancreas, permits an insulin release in response to D
      glyceraldehyde, (D-GA; a glycolytic fuel) and L-leucine or alpha-ketoisocaproic
      acid (alpha-KIC) (non-glycolytic fuels), which alone are not initiators of
      insulin release in this species. 2. The "permissive" effect of D-glucose was also
      observed in the presence of D-mannose (which, as shown herein, is not
      insulinotropic alone). 3. The specificity of glucose for this "permissive" effect
      was, therefore, subsequently questioned in the presence of 10 mM alpha-KIC by
      substituting various glycolytic and non-glycolytic fuels to glucose. 4. D-GA (at
      5 and 15 mM), D-mannose (30 and 50 mM), or the association of L-glutamine + L
      asparagine permitted an insulin release in response to alpha-KIC. 5. The response
      was, however, delayed with D-GA, only occasionally with 50 mM D-mannose, and
      required high concentrations and was delayed in the presence of L-glutamine + L
      asparagine as compared to that obtained with 14 mM D-glucose + alpha-KIC. 6. In
      conclusion, the threshold of fuel-induced insulin release is much higher in the
      chicken than in mammals and this threshold is most efficiently lowered by
      glucose.

PMID- 1361901
TI  - Dietary supplementation of vitamin E fails to prevent the development of
      hyperoxic lung injury in the premature guinea pig.
AB  - 1. The benefit of dietary vitamin E supplementation in preventing oxidative
      induced lung injury was investigated. Three day preterm guinea pig pups were
      exposed to hyperoxic (85% O2) or normoxic (21% O2) conditions. The animals were
      fed either a standard low birthweight human infant formula milk (6.4 mg/l vitamin
      E), or a vitamin E supplemented milk (100 mg/l) for up to 7 days. 2. After 3 days
      vitamin E supplementation, plasma but not erythrocyte vitamin E concentrations
      were elevated, while following 7 days both plasma and erythrocyte vitamin E
      concentrations were significantly increased. 3. Lung and liver vitamin E
      concentrations were elevated at both 3 and 7 days. At 3 days the increase in lung
      vitamin E was oxygen-dependent, suggesting that the lung increases uptake of
      vitamin E in response to oxidative stress. 4. Despite an increase in the vitamin
      E concentration of the lungs of preterm guinea pigs, no amelioration of the lung
      injury was observed. These results suggest that although vitamin E is a potent
      antioxidant, it is unable to protect adequately the lungs from reactive oxygen
      species in the absence of sufficient primary enzymatic antioxidant defences.

PMID- 1361902
TI  - Effect of diet and essential amino acids gavage on young rat amino acid
      metabolism enzymes.
AB  - 1. The effects of a high-fat, high-energy diet and essential plus semi-essential
      amino acid gavage on pup rats have been studied (60-65 animals). 2. The
      activities of alanine transaminase, adenylate deaminase, glutamine synthetase and
      serine dehydratase have been tested in liver and muscle. 3. Plasma was used for
      the estimation of proteins, urea, amino acids, glucose, lactate, 3
      hydroxybutyrate and acetoacetate. 4. Liver and muscle glutamine synthetase
      activities are increased by diet and gavage administered. Hepatic serine
      dehydratase is inhibited by a cafeteria diet but activated by amino acid gavage.
      Adenylate deaminase is inhibited by diet and gavage in the liver, but gavage does
      not affect this enzyme activity in muscle. Liver alanine transaminase is
      increased by the diet; in the muscle, cafeteria diet and amino acid gavage showed
      the highest values for this enzyme. 5. In the plasma, the increase in lactate
      produced by the diet is inhibited by the amino acids provided. Cafeteria-fed pups
      showed lower urea levels and higher 3-hydroxybutyrate concentrations in the
      plasma. 6. Intracellular glucose is diminished by cafeteria diet. In contrast,
      the blood cell amino acid concentration increases with diet and gavage supplied.

PMID- 1361903
TI  - Differential post-receptor responses of adenylate cyclase in white and brown
      adipose tissue membranes of rats fed high-energy diets.
AB  - 1. Adenylate cyclase activity was determined in membranes of white and brown
      adipose tissue (WAT and BAT, respectively) from rats fed a high-energy diet (EXP
      group) vs those fed a nutritionally balanced one (CON group). 2. The
      isoproterenol- and guanine nucleotide-induced adenylate cyclase activity in WAT
      membranes of EXP rats was lower than that in CON rats. 3. Relative adenylate
      cyclase activity in like treated BAT membranes was higher in EXP than in CON
      rats. 4. It is concluded that feeding high-energy diets to rats induces similar
      post-receptor modifications of adenylate cyclase as found in genetic obese
      rodents.

PMID- 1361904
TI  - A microcomputer program for determining turnover rates during non-steady state
      conditions: application to monoamine turnover.
AB  - A program to calculate the turnover rate of monoaminergic neurotransmitters was
      written for use on microcomputers. The program is based on non-steady state
      models, i.e., measuring the rate of change of levels of neurotransmitters or
      their metabolites after pharmacological inhibition of synthetic or degradative
      enzymes. Methods have been developed to estimate monoamine turnover by measuring
      the rate of decrease of catecholamine levels after treatment with alpha-methyl-p
      tyrosine (AMPT), a tyrosine hydroxylase inhibitor, or the increase in serotonin
      levels after pargyline, an inhibitor of monoamine oxidase. This program is
      suitable for examining either linear increases or exponential decreases in
      monoamine levels. The program has been tested in our laboratory for the
      determination of serotonin, dopamine or norepinephrine turnover after hormonal or
      pharmacological manipulations. The program is readily adaptable for calculation
      of the turnover rate of other biological molecules under non-steady state
      conditions.

PMID- 1361905
TI  - Intragastric nicotine protection against 40% ethanol injury in rat stomach. Role
      of ganglionic stimulation or blockade.
AB  - Intragastric nicotine (4 mg/kg) protects against 40% ethanol-induced gastric
      mucosal injury and raises mean blood pressure. We postulated that this protective
      effect was mediated by the ganglionic stimulatory property of nicotine and
      therefore could be abolished by ganglionic blockers. Rats were pretreated with
      intraperitoneal hexamethonium (10 mg/kg) or mecamylamine (2 mg/kg) to block
      peripheral or central autonomic ganglia, respectively. Intragastric vehicle or
      nicotine (4 mg/kg) was then administered. The total lengths of the linear gastric
      corpus mucosal lesions induced by intragastric 40% ethanol were measured by an
      unbiased observer using a caliper. The results showed that both intraperitoneal
      hexamethonium and mecamylamine pretreatments protected against 40% ethanol
      induced gastric mucosal injury. Neither modified the protective effect of
      intragastric nicotine. The protective effect of hexamethonium and mecamylamine
      was associated with a significant increase in the volume of gastric mucus and
      gastric juice. The increase in the volume of gastric content (mucus and juice)
      was partially responsible for the protective effect of these ganglionic blockers.
      In a separate experiment, intraperitoneal nicotine (4 mg/kg) also protected
      against 40% ethanol-induced gastric mucosal injury and raised mean blood
      pressure. These data indicate that the protection against 40% ethanol-induced
      gastric mucosal injury is not unique to intragastric nicotine. Such protection
      can be induced by ganglionic blocking doses of hexamethonium and mecamylamine, or
      a ganglionic stimulatory dose of intraperitoneally administered nicotine. Whether
      ganglionic stimulation or blockade plays a role in the mechanism of intragastric
      nicotine protection, however, remains to be determined.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1361906
TI  - Sequential histologic evaluations in collagenous colitis. Correlations with
      disease behavior and sampling strategy.
AB  - To evaluate the histologic manifestations of collagenous colitis and correlate
      histologic changes with disease behavior, 14 patients who had undergone
      sequential evaluations during 33 +/- 6 months of follow-up were studied. Two
      hundred twelve tissue specimens from all anatomic regions of the colon (mean, 15
      +/- 3 samples per patient) were interpretated independently under code by two
      pathologists. Eight patients (57%) had histologic resolution after 14 +/- 4
      months of empiric therapy and in only one of these (12%) did symptoms persist.
      Four patients (29%) had sequential histologic examinations from the same anatomic
      region that varied from classical collagenous colitis to inflamed mucosa without
      a thickened collagen band to normal mucosa. Eight patients (57%) had varying
      histologic findings from different anatomic regions during the same examination
      that ranged from classical collagenous colitis to increased inflammation with
      resolution of the collagen band to normal mucosa. Normal mucosa was found mainly
      in specimens from the rectosigmoid, and proctosigmoidoscopic examinations alone
      would have missed the diagnosis of collagenous colitis in 40% of cases.
      Pathologic interpretations were concordant in 171 of 212 instances (81%). We
      conclude that histologic resolution of collagenous colitis can occur and it is
      associated with loss of symptoms. The histologic features of collagenous colitis
      are distinctive, but they may be patchy and inconsistently sampled. Rectosigmoid
      biopsies underestimate the diagnosis.

PMID- 1361908
TI  - [Silent myocardial ischemia].

PMID- 1361909
TI  - [National Symposium on Myocardial Ischemia-Reperfusion Injury and silent
      myocardial ischemia].

PMID- 1361907
TI  - Interrelationship between retinal ischaemic damage and turnover and metabolism of
      putative amino acid neurotransmitters, glutamate and GABA.
AB  - Conditions causing a reduction of oxygen availability (anoxia), such as stroke or
      diabetes, result in drastic changes in ion movements, levels of neurotransmitters
      and metabolites and subsequent neural death. Currently, there is no clinically
      available treatment for anoxia induced neural cell death resulting in drastic and
      permanent central nervous system dysfunction. However, there have been some
      exciting developments in experimentally induced anoxic conditions where several
      classes of drugs appear to significantly reduce neural cell death. This report
      aims to provide the foundations for understanding both the basic mechanisms
      involved in retinal ischaemic damage and experimental treatments used to prevent
      such damage. We discuss the normal release, actions and uptake of the fast
      retinal neurotransmitters, glutamate and GABA, in the vertebrate retina.
      Immunocytochemistry is used to demonstrate that both glutamate and GABA are found
      in the macaque retina. Following this is a discussion on how ischaemia may
      enhance neurotransmitter release or disrupt its uptake, thus causing an increase
      in extracellular concentration of these neurotransmitters and subsequent neuronal
      damage. The mechanisms involved in glutamate neurotoxicity are reviewed, because
      excess glutamate is the likely cause of retinal ischaemic damage. Finally, the
      mechanisms behind four possible modes of treatment of neurotransmitter toxicity
      and their advantages and disadvantages are discussed. Hopefully, further research
      in this area will lead to the development of a rational therapy for retinal, as
      well as cerebral ischaemia.

PMID- 1361910
TI  - Perlman and Wiedemann-Beckwith syndromes: two distinct conditions associated with
      Wilms' tumour.
AB  - Though children with Perlman and Wiedemann-Beckwith syndromes have a number of
      features in common, the two conditions are probably separate entities. The
      distinction may not always be easy, however, partly because of the extreme rarity
      of Perlman syndrome, only nine cases of which have been reported so far. We
      report two siblings, initially diagnosed as having Wiedemann-Beckwith syndrome,
      in whom the correct diagnosis of Perlman syndrome was made only after an autopsy
      on the second child. By comparing and contrasting the features of Perlman and
      Wiedemann-Beckwith syndromes in this report we hope to make it easier to
      distinguish the two conditions.

PMID- 1361911
TI  - Guinea pig hepatocyte alpha 1A-adrenoceptors: characterization, signal
      transduction and regulation.
AB  - Activation of guinea pig hepatocyte alpha 1-adrenoceptors increases
      phosphatidylinositol (PI) labeling, [3H]inositol phosphate production and
      phosphorylase activity. These adrenergic actions were not altered by pretreatment
      with chlorethylclonidine but were blocked by 5-methyl urapidil and prazosin (the
      former being 3- to 10-fold more potent than the latter), indicating that alpha 1A
      adrenoceptors were involved. When the cells were incubated in buffer without
      calcium and containing EGTA, the alpha 1A-adrenergic stimulation of PI labeling
      was diminished but not abolished and that of phosphorylase was not affected. The
      alpha 1A-adrenergic effects were insensitive to pertussis toxin treatment.
      Phorbol myristate acetate inhibited the alpha 1A-adrenergic actions, although at
      relatively large concentrations, and also those of other agents such as
      angiotensin II and NaF. Our data clearly indicate that guinea pig hepatocytes
      express alpha 1A-adrenoceptors whose activation stimulates phosphoinositide
      turnover, via a pertussis toxin-insensitive process; the alpha 1A-adrenergic
      effects were at least partially independent of extracellular calcium.

PMID- 1361912
TI  - Idazoxan down-regulates beta-adrenoceptors on C6 glioma cells in vitro.
AB  - Incubation of the C6 cells with 10 microM idazoxan (an alpha 2-adrenoceptor
      antagonist and putative antidepressant) for 5 days in vitro resulted in a 23%
      reduction of beta-adrenoceptor number and a 37% decrease in isoproterenol-induced
      cyclic AMP accumulation. In contrast, post-receptor stimulated cyclic AMP
      accumulation (by the use of forskolin or cholera toxin) was unaffected. The
      desensitization of the beta-adrenoceptor was accompanied by an increase in the
      KL/KH ratio for this receptor. Chronic in vitro treatment of C6 glioma cells with
      idazoxan did not significantly affect cholera or pertussis toxin catalyzed
      ribosylation of Gs and Gi/Go in these cells. Similarly, idazoxan did not alter
      either the basal levels of protein kinase C (PKC) alpha, or its cytoplasm to
      membrane translocation. These results suggest that idazoxan may have direct
      postsynaptic effects, the site of which may be at the level of receptor/G protein
      interaction.

PMID- 1361913
TI  - L-2-amino-4-phosphonobutyrate (L-AP4) is an agonist at the type IV metabotropic
      glutamate receptor which is negatively coupled to adenylate cyclase.
AB  - Glutamate and L-AP4 inhibited forskolin-stimulated cyclic AMP (cAMP) production
      in baby hamster kidney (BHK) cells transfected with the type IV metabotropic
      receptor (mGluR4). In situ hybridization revealed a high level of mRNA for the
      mGluR4 in the entorhinal cortex, but not in the dentate gyrus. These data
      demonstrate that mGluR4 receptors are negatively coupled to the cAMP cascade, and
      suggest that the mGluR4 receptor may be the previously described presynaptic L
      AP4 receptor.

PMID- 1361914
TI  - Effects of drugs acting on Cl(-)-HCO3- and Na(+)-H+ exchangers on acid secretion
      in the rat gastric mucosa sheet preparation.
AB  - The effects of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an
      inhibitor of the Cl(-)-HCO3- exchanger, and amiloride, an inhibitor of the Na(+)
      H+ exchanger, on gastric acid secretion under basal conditions and after
      stimulation with bethanechol or dibutyryl cyclic AMP were studied in rat gastric
      mucosa sheet preparation. DIDS inhibited bethanechol-induced acid secretion in a
      dose-dependent manner, but amiloride had no effect. The stimulation of acid
      secretion by dibutyryl cyclic AMP plus 3-isobutyl-1-methylxanthine was also
      inhibited by DIDs, but not by amiloride. DIDS did not reduce basal acid
      secretion, and neither did amiloride. These results suggest that the Cl(-)-HCO3
      exchanger in the basolateral membrane of the parietal cell plays an important
      role in stimulated gastric acid secretion and that the Na(+)-H+ exchanger is less
      important. In addition, these data show that DIDS inhibits stimulated gastric
      acid secretion irrespective of the secretagogue, but not basal gastric acid
      secretion.

PMID- 1361915
TI  - Differential behavioural and neurochemical effects of competitive and non
      competitive NMDA receptor antagonists in rats.
AB  - The behavioural and biochemical effects of the non-competitive N-methyl-D
      aspartate (NMDA) receptor antagonists, dizocilpine and memantine, and the
      competitive NMDA receptor antagonist, CGP 39551, were investigated in rats.
      Systemic injections of dizocilpine (0.33 mg/kg) increased locomotion and rearing
      in an open field, whereas memantine (20 mg/kg) increased only locomotor activity.
      CGP 39551 (10 and 20 mg/kg) did not change open field activity. Dopamine (DA)
      metabolism--as measured by the ratio of dihydroxyphenylacetic acid/dopamine
      (DOPAC/DA)--increased in response to dizocilpine in the prefrontal cortex and the
      nucleus accumbens. Memantine enhanced DOPAC/DA in the prefrontal cortex, the
      nucleus accumbens and to a lesser degree in the posterior striatum. In contrast
      to non-competitive NMDA receptor antagonists, CGP 39551 did not increase DA
      metabolism of subcortical structures and even decreased DOPAC/DA in the
      prefrontal cortex. These results indicate that competitive and non-competitive
      NMDA receptor antagonists affect spontaneous locomotion differentially in rats.
      The biochemical data imply that the stimulant actions non-competitive NMDA
      receptor antagonists are at least partially due to activation of ascending
      dopaminergic systems. Potential mechanisms involved in the differential effects
      of both types of NMDA receptor antagonists are discussed.

PMID- 1361916
TI  - Calcium channel blocking agents and potassium-stimulated release of glutamate
      from cerebellar slices.
AB  - The effects of calcium channel blockers and tetrodotoxin on the potassium
      stimulated release of endogenous glutamate from rat cerebellar slices was
      assessed. Verapamil (10 microM), omega-conotoxin (1 and 10 microM) and cobalt (2
      mM) all significantly decreased release. Amiloride (100 microM) and tetrodotoxin
      (0.5 and 1 microM) had no effect. The results suggest a role for N-type voltage
      operated calcium channels in the potassium-stimulated release of glutamate.

PMID- 1361919
TI  - [Neurohormonal regulatory mechanisms of the immune system in the course of
      adaptation to high altitude].

PMID- 1361918
TI  - Transfection of murine P19S18 embryonal carcinoma cells with the oncogene neu
      induces an epithelioid phenotype.
AB  - An embryonal carcinoma cell line, P19S18, was transfected with the rat oncogene
      neu to investigate the function of its protein product, p185*, in a
      multipotential cellular environment. Levels of message for p185* were determined
      by in situ hybridization analysis and two highly expressing clones, PnnA and
      PnnB, were isolated. As demonstrated by indirect immunofluorescence and
      immunoprecipitation, these neu-transfected cells synthesized a full length rat
      p185*. The transfectants do not resemble typical embryonal carcinoma cells either
      before or after differentiation is induced by retinoic acid treatment. They are
      much larger, flatter, "epithelioid" cells. These cells have lost the expression
      of stage specific embryonic antigen-1 (SSEA-1), but do synthesize and assemble
      the basement membrane components laminin and fibronectin. These results suggest
      that expression of the neu oncogene in a multipotential cell line may induce the
      synthesis of proteins indicative of an epithelioid phenotype due to the presence
      of p185*.

PMID- 1361917
TI  - Glucagon, insulin and somatostatin secretion in response to sympathetic neural
      activation in streptozotocin-induced diabetic rats. A study with the isolated
      perfused rat pancreas in vitro.
AB  - Changes in glucagon, insulin and somatostatin secretion induced by electrical
      splanchnic nerve stimulation were examined in rats treated with streptozotocin as
      neonates and as adults. In order to study the direct neural effects we used the
      isolated perfused rat pancreas with intact left splanchnic nerve in vitro. In
      normal rats splanchnic nerve stimulation causes significant decreases in insulin
      (30-40%) and somatostatin (30-50%) secretion at both 16.7 mmol/l and 1 mmol/l
      glucose concentrations. In the neonatal streptozotocin-diabetic rat splanchnic
      nerve stimulation at 16.7 mmol/l glucose decreased insulin secretion (14%)
      further than in the control rats (30%), however, somatostatin secretion did not
      decrease to the same extent. Similar results were also observed at the low (1
      mmol/l) glucose concentration. On the other hand, percent decreases of insulin
      and somatostatin secretion induced by splanchnic nerve stimulation in the
      streptozocin-diabetic rats were similar to the values observed in the normal
      control rats. The glucagon secretion in response to splanchnic nerve stimulation
      at 16.7 mmol/l glucose from pancreatic Alpha cells in both types of induced
      diabetes is exaggerated, and the degree of exaggeration seems to parallel the
      severity of the hyperglycaemia. However, the splanchnic nerve stimulation-induced
      glucagon secretion at 1 mmol/l glucose was impaired in the streptozotocin
      diabetic rats, but not in the neonatal streptozotocin-diabetic rats. These data
      suggest that the sensitivity of diabetic Alpha and Delta cells to sympathetic
      neural activation are blunted, whereas the sensitivity of Beta cells is enhanced
      in the diabetic animal model.

PMID- 1361920
TI  - Regression of duodenal gastrinomas in a patient with multiple endocrine neoplasia
      type I after parathyroidectomy.

PMID- 1361921
TI  - [Polymorphism of untranscribed spacer rDNA as a molecular genetic marker in
      population studies of cattle].
AB  - Variable polymorphic patterns were detected using EcoRI-SalI fragment of bovine
      rDNA, including 3'-end of 28S rRNA gene with the adjacent portion of the
      transcribed spacer, as a probe for hybridization. Some features of these
      polymorphic patterns are similar to DNA fingerprints detected with the M13 probe.
      Bovine rDNA spacer polymorphism was used as a molecular genetic marker for
      population analysis of individual specific patterns of 4 cattle breeds with the
      help of the Jeffreys' method. It was supposed that the probability of identical
      fingerprints appearance could be the characteristics of heterogeneity of cattle
      populations. The observed length of polymorphic gragments ranged from 2000 to
      6000 bp. The mean number of fragments per individual for all breeds was 15.05.
      The probability of identical patterns appearance was very high: from 1.18 x 10(
      5) in ajshir's breed to 1.43 x 10(-7) in "white and black"s' breed. So, high
      probability seems to be dependent on the high allelic frequency and the way of
      breeding.

PMID- 1361923
TI  - [Uses in surgery of the hormone somatostatin and its synthetic analogues].

PMID- 1361922
TI  - [Genetic differentiation of the Mongolian population. Comparative analysis of the
      geographic distribution of biochemical markers of genes and restriction fragment
      length polymorphism of nuclear DNA in the Mongolian population].
AB  - The geographical distribution of the gene frequencies from loci: Hp, Tf, Gc, Pi,
      AcP1, GLO1, EsD, 6-PGD, PGM1 and RFLP's of the nuclear DNA of the loci HBG-2
      (HindIII), HBB (AvaII), ApoB (XbaI), D7S8 (PstI), LDLR (HincII) and AT-3 was
      analysed in the Mongolian population. These data revealed the homogeneity of 18
      local groups in Mongolia and extremely low genetic differences measured by GST.
      There was no differences in the average GST values between protein markers and
      nuclear DNA markers.

PMID- 1361924
TI  - A possible mechanism for the increase in brain tyrosine levels induced by cyanide
      in mice.
AB  - Subcutaneous administration of cyanide significantly increased blood tyrosine
      levels of mice in a dose dependent manner. Tyrosine aminotransferase activity in
      liver of mice was significantly decreased in the presence of cyanide (8, 10, 20,
      40, 50, 65, 80 and 100 microM), also in a concentration-dependent manner, with a
      positive correlation between the percentage increase of blood tyrosine levels and
      the percentage decrease of hepatic tyrosine aminotransferase activity. These
      results suggest that the increased tyrosine levels induced in blood by cyanide
      may be related to its inhibition of tyrosine aminotransferase activity in the
      liver. Cyanide decreased hepatic ATP content and increased blood ammonia levels
      and brain tyrosine in a dose-dependent manner. As it is known that
      hyperammonaemia increases the uptake of neutral amino acids such as tyrosine into
      the brain from blood, the mechanism by which tyrosine levels increase in the
      brain may be based on increases of both tyrosine and ammonia levels in blood.

PMID- 1361925
TI  - 4th European Meeting on Complement in Human Disease. Noordwijkerhout, The
      Netherlands, 1-4 May 1992.

PMID- 1361926
TI  - [Ammonium bituminosulfonate (Ichthyol). Anti-inflammatory effect and inhibition
      of the 5-lipoxygenase enzyme].
AB  - Ammonium bituminosulphonate (Ichthyol) inhibits 5-lipoxygenase activity in human
      polymorphonuclear neutrophils. The inhibition is dose-dependent and occurs at non
      cytotoxic concentrations of the drug. This results in a decreased release of
      Leukotriene B4 from polymorphonuclear neutrophils. Furthermore, when applied to
      the ear skin of AB/Bln mice pretreated with croton oil, Ichthyol reduces the
      inflammatory reaction.

PMID- 1361927
TI  - [Intralesional treatment of classical Kaposi sarcoma with interferon-alpha].
AB  - A 71-year-old female patient with classic Kaposi sarcoma (sarcoma idiopathicum
      haemorrhagicum multiplex) of the lower legs and one hand was treated with
      intralesional recombinant interferon alpha 2b. After 6 consecutive weeks of
      intratumoral injection of 1-3 million IU interferon-alpha 2b (Intron A) in three
      marked lesions, complete remission of intralesionally treated and of untreated
      tumours was observed. Even 9 months after treatment, the patient is still in
      complete remission. We conclude that this low dose and well-tolerated treatment
      schedule with interferon-alpha 2b is effective and a good alternative to
      radiation or chemotherapy in Kaposi sarcoma.

PMID- 1361928
TI  - Analysis and pharmacokinetics of cimaterol in growing Holstein steers.
AB  - Pharmacokinetic parameters for the beta 2-adrenergic agonist, cimaterol (CIM),
      were determined in growing Holstein steers. Compartmental analysis was used after
      measurement of CIM in body fluids by affinity chromatography and HPLC using UV
      detection. Recoveries from spiked plasma and urine standards were 70 +/- 1.2% and
      68 +/- 1.1%, respectively. The minimum detection level in plasma was 1 ng/mL and
      the average CV was 5.1% for concentrations that ranged from 1 to 30 ng/mL. Four
      steers (276 +/- 24 kg) received 15 mg of CIM by bolus intravenous injection.
      Plasma CIM levels declined in a biphasic manner with half-lives of 2.5 min for
      the distribution phase and 54 min for the elimination phase. A two-compartment
      open model was used to describe the disappearance of CIM and the following
      pharmacokinetic parameters were obtained: central compartment volume (Vc) = .76
      L/kg, apparent volume of distribution (Vd) = 4.1 L/kg, and transfer rate
      constants from the central to peripheral compartment (k12) = .177/min, from the
      peripheral to central compartment (k21) = .054/min and elimination from the
      central compartment (kel) = .074/min. After 8 h, total urinary CIM accounted for
      only 18.3% of the administered dose. Results suggest that circulating
      concentrations of CIM in growing steers are influenced by its accumulation in an
      unidentified peripheral pool and its conversion into unknown metabolite(s) before
      elimination.

PMID- 1361929
TI  - Changes in activities of lipogenic enzymes in adipose tissue and liver of growing
      goats.
AB  - The lipogenic capacity of omental adipose tissue and liver was measured in vitro
      from samples obtained at slaughter from 33 young male goats. The animals were
      slaughtered either on the day of weaning (d 0) or 2, 14, or 56 d after weaning.
      Ages at weaning were 4 wk (early weaning) or 6 or 8 wk (late weaning). Blood
      samples from the jugular vein were taken before slaughter to measure the
      concentrations of plasma glucose and nonesterified fatty acids. There was a 30%
      decrease in glucose concentration after weaning. Nonesterified fatty acid
      concentration increased fourfold between d 0 and 2 after weaning. By d 14 after
      weaning, nonesterified fatty acids returned to basal concentration. The
      lipoprotein lipase (LPL) activity of adipose tissue declined markedly (90%) on d
      2 after weaning. Lipoprotein lipase activity returned to preweaning values by d
      56 after weaning in those goats that had ad libitum access to feed. In adipose
      tissue, nicotinamide adenine dinucleotide phosphate (NADP)-malate dehydrogenase
      activity fell by only 17% by d 2 after weaning and to 63% by d 14 after weaning.
      Lipoprotein lipase activity was closely related to metabolizable energy intake
      the day before slaughter. Acetyl-coenzyme A carboxylase activity was low in
      adipose tissue and it increased only slightly by d 56 after weaning. The data
      indicated that LPL played a preponderant role in the restoration of lipid stores
      after weaning. High NADP-malate dehydrogenase activity together with a high
      concentration of plasma glucose by d 56 after weaning suggested that this enzyme
      activity could be enhanced by high glucose availability in goat kids. Activities
      of lipase, acetyl-coenzyme A carboxylase, NADP-malate dehydrogenase, and glucose
      6-phosphate dehydrogenase in liver were essentially unaffected by weaning. The
      extent and rapidity of change of lipogenic enzymes of goat kids was much more
      pronounced in adipose tissue than in liver.

PMID- 1361930
TI  - Pulmonary vasodilation by inhaled nitric oxide after endothelial injury.
AB  - Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally
      induced pulmonary vasoconstriction. To examine the effect of free radical injury
      and methylene blue exposure on inhaled NO-induced pulmonary vasodilation we
      studied ventilated rabbit lungs perfused with Krebs solution containing 3%
      dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture
      for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by
      the thromboxane analogue U-46619 was significantly reduced [8 +/- 2 (SE) mmHg].
      Acetylcholine similarly reduced Ppa (9 +/- 1 mmHg). After free radical injury and
      methylene blue exposure, inhaled NO again produced significant vasodilation (5 +/
      1 and 9 +/- 2 mmHg, respectively), but acetylcholine resulted in an increase in
      Ppa (-9 +/- 3 and -4 +/- 1 mmHg, respectively). These data demonstrate that
      pulmonary vasodilation produced by inhaled NO is unaffected by free radical
      injury or methylene blue in the intact lung despite concomitant reversal of
      acetylcholine-induced vasodilation.

PMID- 1361931
TI  - Effects of nebivolol stereoisomers on the action of adrenaline on blood pressure,
      heart rate and blood levels of noradrenaline and DOPEG.
AB  - 1. Nebivolol (a new beta 1-adrenoceptor blocking drug) has particular effects on
      the cardiovascular system, i.e. it induces hypotension without affecting cardiac
      function or increasing peripheral vascular resistances. In this study, we aimed
      to evaluate the effects of nebivolol and its stereoisomers on the actions of
      adrenaline (AD) at the cardiovascular level as well as at the prejunctional level
      (as ascertained by modification of noradrenaline (NA) and dihydroxyphenylglycol
      (DOPEG) plasma levels in the anaesthetized dog. 2. AD infusion (0.1 micrograms kg
      1 min-1) did not induce statistically significant changes in mean blood pressure
      and heart rate; it caused a pronounced and sustained rise of AD levels, no
      significant alterations in NA levels and a marked, progressive and sustained
      increase in DOPEG levels. 3. Mean blood pressure was not affected by any of the
      nebivolol isomers. d- and dl-nebivolol in the two doses used (0.3 and 0.03 mg kg
      1 in 15 min) caused a significant and dose-dependent decrease in heart rate.
      Plasma levels of AD and NA were not changed by any of the nebivolol isomers
      tested. However, all of them significantly reduced the increase in plasma levels
      of DOPEG induced by adrenaline infusion. 4. We conclude (1) that AD infusion in
      the dog facilitates NA release and that DOPEG is a good index of this effect; and
      (2) nebivolol appears to act at the prejunctional level, reducing the increase in
      NA release induced by adrenaline, as shown by the effect on DOPEG plasma levels.

PMID- 1361932
TI  - Role of nitric oxide in the autonomic innervation of smooth muscle.

PMID- 1361933
TI  - A one-tube, one manipulation RT-PCR reaction for detection of Ross River virus.
AB  - A sensitive, single tube reverse transcription-polymerase chain reaction (RT-PCR)
      protocol for the detection of Ross River virus (RRV) is described. All components
      necessary for both reverse transcription and PCR were combined in a single tube,
      and reverse transcription and PCR carried out sequentially in a single, non
      interrupted thermal cycling program. The antisense oligonucleotide from the two
      primers selected for use in the PCR also served to prime specifically for the
      reverse transcription. The 549 bp product was detected by electrophoresis and
      ethidium bromide staining. The detection limit using this system was 18 fg of
      purified viral RNA or 1.3 pfu of whole virus. Greater sensitivity cannot
      reasonably be expected unless a more sensitive method than electrophoresis and
      ethidium bromide staining is used for PCR product detection, such as nested PCR
      or hybridisation with labelled probe. This PCR detection system will be adapted
      for detection of RRV in mosquito populations for virus surveillance programs.

PMID- 1361934
TI  - Symposium on Sudden Infant Death Syndrome. London, 23 January 1992.

PMID- 1361935
TI  - Impact of chronic oral H2-antagonist therapy on left ventricular systolic
      function and exercise capacity.
AB  - It has been suggested that H2-antagonists may adversely affect left ventricular
      systolic function. To assess the effects of cimetidine, famotidine, and
      ranitidine on exercise capacity and left ventricular systolic function, the
      authors conducted a randomized, double-blind, four-way crossover study in 15
      healthy male volunteers with placebo control. Each subject underwent a maximal
      upright treadmill exercise test, aerobic metabolic assessment, and two
      dimensional stress echocardiography on six separate occasions. The initial two
      treadmill exercise tests with aerobic metabolic assessment and stress
      echocardiography were performed to minimize the learning effect. In the final
      four evaluations, subjects were randomized to receive 7 days of oral treatment
      with cimetidine 400 mg twice daily, famotidine 40 mg daily, ranitidine 150 mg
      twice daily, and placebo. A comparison of exercise tests, aerobic metabolic
      assessment, and stress echocardiography results found no significant differences
      between any of the H2-antagonists and placebo. In addition, there were no
      significant differences in test results between cimetidine, famotidine, and
      ranitidine. Specifically, exercise treadmill time, maximal oxygen consumption,
      respiratory quotient, maximal exercise systolic and diastolic blood pressure,
      maximal exercise heart rate, left ventricular end-diastolic dimension, left
      ventricular end-systolic dimension, and ejection fraction were not different
      between treatments. The authors conclude that 7 days of oral treatment with
      cimetidine, famotidine, or ranitidine has no deleterious effect on exercise
      capacity or left ventricular systolic function in healthy subjects.

PMID- 1361936
TI  - Benzodiazepines and other psychotropic drugs abused by patients in a methadone
      maintenance program: familiarity and preference.
AB  - Physicians often face the problem that they have to treat anxiety and insomnia in
      patients who are dependent on narcotics or other substances. Reports about
      different reinforcing properties of different benzodiazepines and increasing
      concern about their misuse, often in combination with other drugs, call for
      studies that help to establish recommendations for choosing psychopharmacologic
      agents in the treatment of these patients. Opiate addicts enrolled in a methadone
      maintenance program were interviewed about their subjective "liking" of all
      psychotropic substances with which they had personal experience. The results
      confirm previous reports that certain benzodiazepines, especially flunitrazepam
      and diazepam, stand out from others in terms of positive reinforcing properties.
      Overall, the attractiveness of benzodiazepines as drugs of abuse for poly-drug
      abusers is lower than that of other sedative/hypnotics.

PMID- 1361937
TI  - Encapsulation and pilus formation of Bacteroides spp. in normal flora abscesses
      and blood.
AB  - The presence of encapsulated and piliated Bacteroides spp. (mostly Bacteroides
      fragilis and melaninogenicus groups was investigated in isolates from blood,
      abscesses and normal flora. Of the strains of Bacteroides spp. isolated 45 of 54
      (83%) recovered from blood and 31 of 40 (78%) found in abscesses were
      encapsulated. In contrast, only seven of 71 (10%) similar strains isolated from
      the faeces or pharynx of healthy persons were encapsulated (P < 0.001). Pili were
      observed in three of 54 (6%) of strains isolated from blood, 30 of 40 (75%) of
      those recovered from abscesses (P < 0.001), and 49 of 71 (69%) of those found in
      normal flora (P < 0.001). The predominance of encapsulated forms in all strains
      of B. fragilis and B. melaninogenicus in blood as well as in abscesses suggests
      an increased virulence of these compared with non-encapsulated isolates. In
      contrast, the presence of pili in Bacteroides spp. recovered mostly from
      abscesses and normal flora suggests that this structure may play a role in the
      ability of these organisms to adhere to mucous membranes and may interfere with
      their ability to spread systemically. These findings illustrate the morphological
      differences that may be observed in Bacteroides spp. from various anatomical
      sites.

PMID- 1361938
TI  - Typing by DNA probe of mycobacterial species isolated from patients with AIDS.
AB  - Restriction fragment length polymorphism (RFLP) types of Mycobacterium avium
      intracellulare and Mycobacterium kansasii isolated from patients with AIDS were
      examined. We demonstrate that one RFLP type is much more common than others which
      confirms previous findings. Carriage of individual RFLP types is constant over
      long periods of time. In addition, we document a disseminated infection in a
      patient with M. avium intracellulare of three RFLP types.

PMID- 1361939
TI  - Musculoskeletal symptomatology in some HIV-positive injecting drug users may be a
      manifestation of the benzodiazepine withdrawal syndrome.

PMID- 1361940
TI  - Efficacy of Bacillus sphaericus against the malaria vector Anopheles gambiae and
      other mosquitoes in swamps and rice fields in Zaire.
AB  - The microbial control of Anopheles gambiae and other mosquitoes with a granular
      formulation of Bacillus sphaericus (Vectolex) was evaluated in rice fields and
      swamps, located around the suburban region of Kingabwa-village in Kinshasa,
      Zaire. Ten treatment cycles with 15-day intervals were carried out with the same
      application rate, 10 kg/ha, during the dry season (May to September 1991). The
      treatments reduced larval populations of An. gambiae by 98% after 48 h, but
      repetitive applications were required every 15 days to maintain control. The
      persistence of B. sphaericus spores was more apparent in rice fields than in
      swamps. A significant reduction in nuisance biting by Culex quinquefasciatus and
      Mansonia uniformis was observed. For An. gambiae, a decrease of 13.6% in human
      biting was noted during the post-treatment period. The entomological inoculation
      rate was reduced from 0.238 to 0.143. The efficacy of B. sphaericus does not
      appear to offer outstanding potential for control of An. gambiae in rice fields
      and swamps and seems to be limited due to different factors tied to ecology and
      natural conditions in the fields.

PMID- 1361941
TI  - A fabric body light trap for sampling mosquitoes.
AB  - A Fabric Body light trap has been developed that has unique features of a cloth
      body, folding rainshield and a modified folding net. These features allow the
      light trap to be reduced in size and weight for transportation and storage while
      retaining the same operational characteristics as the Solid State Army Miniature
      (SSAM) light trap.

PMID- 1361942
TI  - Reduced mosquito production in cemetery vases with copper liners.
AB  - Water-holding stone vases were sampled in 4 central Florida cemeteries to compare
      the prevalence of mosquitoes in containers with and without metallic liners.
      Overall, immature mosquitoes were found in more than 60% of the vases lacking
      liners and in more than 50% of the vases with aluminum liners. Significantly
      fewer vases with copper liners were positive for mosquitoes. High mortality and a
      lack of development were observed in a field test involving the introduction of
      Aedes aegypti larvae into stone vases with copper liners.

PMID- 1361943
TI  - A survey of larval mosquitoes on Kume Island, Ryukyu Archipelago, Japan.
AB  - Mosquito collections were carried out during May 1991 in Kume Island, Ryukyu
      Archipelago. Eighteen species of mosquitoes in 8 genera were collected; 11
      species were new records for Kume Island. Characteristics of the larval habitats
      of these species are also described.

PMID- 1361944
TI  - Effect of antibiotic treatment on mycelial growth of isolates of the mosquito
      pathogenic fungus Lagenidium giganteum (Oomycetes: Lagenidiales) from Australia,
      Colombia and United States.
AB  - Bacteria collected in mosquito breeding ponds were evaluated for resistance to
      streptomycin, chloramphenicol, penicillin and trimethoprim. Mycelial growth of
      Lagenidium giganteum isolates from Australia, United States and Colombia were
      evaluated in PYG media containing one antibiotic or a mixture of these compounds.
      Media containing chloramphenicol reduced mycelial growth of most of the isolates.
      The antibiotic mixtures and penicillin-streptomycin penicillin-trimethoprim did
      not significantly affect mycelial growth of the isolates; however, the later
      substantially reduced bacterial contamination.

PMID- 1361945
TI  - A comparison of T4:T8 lymphocyte ratio in the periodontal lesion of healthy and
      HIV-positive patients.
AB  - Previous reports describe a characteristic, rapidly progressive, periodontitis
      that is unique to patients who are seropositive for HIV antibody (Western blot
      +). The purpose of this study was to compare the T4 and T8 lymphocyte
      subpopulations in the peripheral blood and periodontal lesions of these HIV
      patients with those of healthy controls. T-cell subsets in peripheral blood were
      quantified by flow cytometry. The values from this analysis were used to
      calculate the peripheral T4:T8 lymphocyte ratio for each patient. Gingival tissue
      (papilla) was obtained from 8 HIV+ patients and from 6 healthy HIV- control
      patients during routine gingival surgery. The T-cell subpopulations in the
      gingival tissue were determined using serial cryostat sections that were labeled
      with monoclonal antibodies for T4 and T8 cells and developed using an avidin
      biotin-peroxidase system. Six sections were taken from each of the 14 tissue
      specimens (one per patient). The sections were examined at 450 x and the mean
      number of T4 and T8 cells calculated for each section. These mean values were
      then used to determine the T4:T8 lymphocyte ratio for each tissue specimen. The
      peripheral blood analysis revealed a mean serum T4:T8 ratio of (2.07 +/- 0.455)
      for the controls and (0.58 +/- 0.26) for the HIV patients. The significantly
      lower T4:T8 ratio in HIV patients is consistent with their diagnosis. Although
      the results indicated that the mean T4:T8 lymphocyte ratio in the gingiva of
      controls was highly variable (2.70 +/- 1.344), the gingiva of HIV patients
      consistently exhibited a complete absence of T-cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1361947
TI  - A puncture wound complicated by infection with Edwardsiella tarda.

PMID- 1361946
TI  - Opioid receptor affinity for agonist-antagonist analgesics.
AB  - Analgesic medications are distributed to a variety of receptors within the
      central nervous system. Activity at these receptors (mu 1, mu, sigma, delta,
      kappa) results in both the beneficial pain-relieving effects of analgesics as
      well as undesirable side effects. The mixed agonist-antagonist class of
      analgesics offers the potential benefit of greater receptor site selectivity
      while diminishing the incidence of adverse sequelae, such as respiratory
      depression. Traditionally, it has been suggested that mixed agonist-antagonist
      medications may be associated with decreased analgesic effectiveness. However,
      newer agents of this mixed class may result in effective analgesia while
      diminishing the incidence of side effects.

PMID- 1361948
TI  - Spinal cord compression in polyarteritis nodosa.

PMID- 1361949
TI  - Role of B13 Glu in insulin assembly. The hexamer structure of recombinant mutant
      (B13 Glu-->Gln) insulin.
AB  - The assembly of the insulin hexamer brings the six B13 glutamate side-chains at
      the centre into close proximity. Their mutual repulsion is unfavourable and zinc
      co-ordination to B10 histidine is necessary to stabilize the well known zinc
      containing hexamers. Since B13 is always a carboxylic acid in all known sequences
      of hexamer forming insulins, it is likely to be important in the hormone's
      biology. The mutation of B13 Glu-->Gln leads to a stable zinc-free hexamer with
      somewhat reduced potency. The structures of the zinc-free B13 Gln hexamer and the
      2Zn B13 insulin hexamer have been determined by X-ray analysis and refined with
      2.5 A and 2.0 A diffraction data, respectively. Comparisons show that in 2Zn B13
      Gln insulin, the hexamer structure (T6) is very like that of the native hormone.
      On the other hand, the zinc-free hexamer assumes a quaternary structure (T3/R3)
      seen in the native 4Zn insulin hexamer, and normally associated only with high
      chloride ion concentrations in the medium. The crystal structures show the B13
      Gln side-chains only contact water in contrast to the B13 glutamate in 2Zn
      insulin. The solvation of the B13 Gln may be associated with this residue
      favouring helix at B1 to B8. The low potency of the B13 Gln insulin also suggests
      the residue influences the hormone's conformation.

PMID- 1361951
TI  - Abstracts from the 3rd Japanese Neurotrauma Symposium. Tokyo, Japan, September
      21, 1991.

PMID- 1361950
TI  - Morphologic changes in cultured astrocytes after exposure to glutamate.
AB  - Cultured astrocytes, exposed to glutamate at a dose that is generally neurotoxic
      in vitro (1 mM), exhibit transient swelling in the absence of cell death. In the
      present study, we further characterize this response by examining the
      distribution of intermediate filaments and evaluating cellular ultrastructure in
      primary cultures of astrocytes after exposure to 1 mM glutamate. In addition,
      cellular swelling was determined using the nonmetabolizable hexose 3-O-methyl
      [14C]-glucose (3-MG). Glial fibrillary acidic protein (GFAP) was immunolocalized
      at the light microscopic level to study the distribution of intermediate
      filaments. GFAP was immunolocalized to a fine cytoskeletal network in control
      cultures. Four to 24 h after exposure to glutamate, this detailed localization
      was replaced by a diffuse, uneven pattern of immunoreactivity. The most prominent
      ultrastructural changes were identified at 4 and 8 h after glutamate exposure.
      Nucleoli underwent transformation from a normal compact appearance to a markedly
      dispersed state. The cell body typically exhibited cytoplasmic lucency, swollen
      mitochondria, and dilated cisterns. Intermediate filaments within cellular
      processes appeared widely spaced in comparison to the controls. These
      ultrastructural changes coincided with findings of increased intracellular water
      space as determined with 3-MG. These findings demonstrate that astrocytes exposed
      to 1 mM glutamate exhibit transient morphologic changes that not only suggest
      cellular swelling but also define a more diverse response that is reflected in
      the altered immunolocalization of GFAP and in unique changes in the nucleolus.

PMID- 1361952
TI  - Selective effect of chronic lead ingestion on tyrosine hydroxylase activity in
      brain regions of rats.
AB  - Alterations of tyrosine hydroxylase activity in various regions of brain from
      rats postnatally exposed to lead were tested. Three groups of animals were
      prepared; (1) Rats exposed to lead at a low dose (0.05% lead acetate, PbAc); (2)
      Rats exposed to lead at a high dose (0.2% PbAc); (3) Age-matched normal control
      rats. At 2, 4, 6, and 8 weeks of age, weight of brain and body, and
      concentrations of lead in whole brain of animals in each group were measured.
      Activities of tyrosine hydroxylase and Na(+)-K+ ATPase were also measured at the
      same ages in 4 brain regions of each animal. Body weight gain was decreased after
      6 weeks of age in rats exposed to lead at a high dose. Concentrations of lead in
      whole brain were increased from 0.37 to 0.83 (ng/mg wet tissue) in these animals.
      Exposure of rats to lead generally increased tyrosine hydroxylase activity and
      decreased Na(+)-K+ ATPase activity. However, changes of tyrosine hydroxylase
      activity were detected without concomitant changes of Na(+)-K+ ATPase activity in
      pons-medulla at 2 weeks of age and telencephalon at 6 weeks of age in rats
      exposed to lead at a low dose, and in midbrain at 4 and 6 weeks of age in rats
      exposed to lead at a high dose. These data imply that catecholaminergic nervous
      system in the brain regions described above could be selectively affected by
      lead.

PMID- 1361953
TI  - Effects of hexamethonium on bradycardiac responses to brain ischemia in the
      rabbit.
AB  - The present study investigated the bradycardiac responses to brain ischemia for
      approximately 30s before and after intravenous administration of hexamethonium
      (C6, 15 mg/kg) in urethane-anesthetized spontaneously breathing rabbits. The
      brain ischemia was performed by clamping both common carotid arteries in rabbits
      whose vertebral arteries were previously occluded. The brain ischemia caused
      bradycardia, pressor response and apnea. Administration of C6 blocked the
      bradycardia evoked by brain ischemia and reduced pressor response at the initial
      period after the onset of brain ischemia. The brain ischemia-induced apnea was
      not significantly altered by C6-treatment. In a separate series of experiments,
      we examined the effects of C6 on the response of heart rate (HR) to vagal
      stimulation in rabbits following unilateral vagotomy. Electrical stimulation of
      the peripheral end of the cut left vagus nerve that selectively activated
      myelinated fibers caused the bradycardia and this effect was entirely blocked by
      administration of C6. When the intensity of stimulus to activate both myelinated
      and non-myelinated fibers was increased, part of the bradycardia was retained
      following C6 administration. These results suggest that the brain ischemia
      induced bradycardia is totally mediated through the activation of myelinated
      efferent fibers in the vagus nerve.

PMID- 1361955
TI  - [European Gastroenterology Week].

PMID- 1361954
TI  - [int-2 and c-erbB-2 gene amplification in urological cancers].
AB  - We analyzed the alteration of int-2, c-erbB-2 and EGFR genes in 32 cases of
      transitional cell carcinoma of the urinary tract, 15 cases of renal cell
      carcinoma and 14 cases of prostatic carcinoma by Southern blot hybridization
      method. Three- to 12 fold amplification of int-2 gene was observed in 4 (12.5%)
      of 32 transitional cell carcinomas. Of these 4 cases 3 were G3 tumor with muscle
      invasion and the remaining was G1, pTa tumor with subsequent recurrence of
      multiple tumors. The other 2 cases (6.3%) with invasive transitional cell
      carcinoma showed amplification of c-erbB-2 gene. Neither amplification nor gross
      rearrangement of EGFR gene was detected in transitional cell carcinoma. On the
      other hand, renal cell carcinomas and prostatic carcinomas had neither
      amplification nor gross rearrangement of these 3 genes. These results suggest
      that the int-2 gene located in chromosome locus 11q13 and the c-erbB-2 gene have
      a specific role in carcinogenesis and in progression of transitional cell
      carcinoma through their gene amplifications.

PMID- 1361957
TI  - A specific enzyme assay for aminopeptidase M in rat brain.
AB  - A specific enzyme assay for aminopeptidase M (APM) activity on rat brain
      membranes has been developed through selective use of enzyme inhibitors.
      Amastatin was the most potent inhibitor (amastatin > actinonin > MDL73347 >
      bestatin) for purified porcine kidney APM, giving 98% inhibition at a 6 microM
      concentration, while actinonin, yielded only 57% inhibition at this
      concentration. Puromycin (10 microM) was used to inhibit puromycin-sensitive
      aminopeptidase activity in the rat brain membrane preparation. Puromycin (10
      microM) had only a slight effect on the Km of porcine kidney APM, and had
      negligible effect on APM velocity at the high substrate concentration (2 mM) used
      in the APM assay. The assay produced a linear accumulation of product for
      increasing amount of rat brain membranes used, and for increasing incubation
      time. The Km of APM on rat brain membranes for L-Leucine-p-nitroanilide (0.383
      mM) was similar to the Km of purified porcine kidney APM (0.558 mM). APM
      activity, involved in the metabolism of several biologically important
      neuropeptides in different brain regions, can be specifically measured with this
      enzyme assay.

PMID- 1361956
TI  - NMDA-, but not kainate- or quisqualate-dependent increases in cerebellar cGMP are
      dependent upon monoaminergic innervation.
AB  - As previously reported, intracerebellar injections of D-serine, quisqualate and
      kainate elevated mouse cerebellar cGMP levels. Similarly, activation of
      endogenous excitatory amino acid utilizing neurons with harmaline or
      pentylenetetrazole also increased cerebellar cGMP. We previously have
      demonstrated that the harmaline- and pentylenetetrazol-dependent cGMP increases
      are NMDA receptor mediated. In this report we further demonstrate that NMDA
      dependent increases in cGMP are dependent upon monoaminergic innervation of the
      cerebellum, while kainate- and quisqualate-dependent cGMP increases are
      independent of such innervation.

PMID- 1361958
TI  - Studies on novel pili from Shigella flexneri. I. Detection of pili and
      hemagglutination activity.
AB  - Pili were detected using electron microscopy in clinical isolates of Shigella
      flexneri which had been continuously subcultivated in liquid media.
      Morphologically, the pili appeared as thin, flexible, cylindrical structures of
      up to 2-5 microns in length and about 3-5 nm in diameter. Two strains showed
      mannose-resistant (MR) hemagglutination to fresh fowl erythrocytes (type 4), and
      one to tannic acid-treated horse erythrocyte (type 3) pili. These pili are novel
      and different from the mannose-sensitive (MS) type 1 pili described by Duguid and
      Gillies.

PMID- 1361959
TI  - A comprehensive macrophage-T-lymphocyte theory of schizophrenia.
AB  - Chronic macrophage activation with subsequent failure of activated macrophages to
      properly control T-lymphocyte secretion of interleukin-2 and interleukin-2
      receptors is proposed as the basic biological mechanism of schizophrenia.
      Fundamental to this theory are the clinical observations on interleukin-2
      provoking the active phase symptoms of schizophrenia in psychiatrically normal
      human volunteers and macrophage cytokines producing the prodromal and residual
      phase symptoms. This theory provides a completely new and unified mechanisms for
      the antipsychotic action of typical and atypical neuroleptics, bromocriptine,
      naloxone and DMSO. Furthermore, this hypothesis reveals why the dopamine theory
      of schizophrenia was a false lead. The effects of prolactin, estrogens and
      androgens are consistent with the model. Age of onset, male/female incidence,
      course of the disease from prodromal to active to residual phase, the protection
      afforded by rheumatoid arthritis and the close relationship between depression
      and schizophrenia can be explained by this theory. The gastrointestinal tract is
      suggested as the preferred site to investigate for the cause of the immune
      activation in schizophrenia.

PMID- 1361960
TI  - [Pharmacokinetics of broxaterol in asthmatic children].
AB  - Pharmacological profile of broxaterol, a new beta adrenergic compound, was
      investigated in 12 asthmatic children (6 male and 6 female with age 8-13 years).
      This study was performed from November to May, and venous blood was collected
      after 30, 45, 120, 180, 240 minutes from administration of 0.5 mg broxaterol; the
      urine was collected every 4 hours drug intake (0-4, 4-8, 8-12 hours). Drug
      absorption proved very fast: T max was 0.9 hours and Cmax was 2.05 micrograms/ml.
      T 1/2 was 2.3 hours. The urine concentration of broxaterol in the urine 0-4 and 4
      8 hours after administration, was 6.11 and 2.3% (as drug percentage), after 8
      hours no broxaterol was evaluated in the urine. Pharmacological profile of
      broxaterol in asthmatic children and adults is comparable.

PMID- 1361961
TI  - PCR detection and differentiation of Chlamydia pneumoniae, Chlamydia psittaci and
      Chlamydia trachomatis.
AB  - A PCR-based system was developed for the detection and differentiation of
      Chlamydia trachomatis, Chlamydia psittaci and Chlamydia pneumoniae. A conserved
      145 bp fragment of the chlamydial omp1 gene was amplified from all three species.
      The three species were then differentiated from each other by digestion of this
      PCR product with restriction enzymes Eco RI and either Hind III or Pst I. The
      system was shown to work for two strains of C. pneumoniae, 11 strains of C.
      psittaci and 10 serovars of C. trachomatis, and had a sensitivity of less than 10
      chlamydial elementary bodies. This method was also applicable to the detection of
      C. trachomatis in conjunctival and nasopharyngeal swabs.

PMID- 1361962
TI  - Distinguishing Chlamydia species by restriction analysis of the major outer
      membrane protein gene.
AB  - Clinical isolates of Chlamydia pneumoniae from diverse geographic locations and
      strains of other Chlamydia species were typed by polymerase chain reaction (PCR)
      amplification of the major outer membrane protein (MOMP) gene followed by
      restriction fragment length polymorphism analysis of the product. Use of
      synthetic primers corresponding to highly conserved regions of the MOMP gene
      resulted in amplification of a 1070 bp product in laboratory strains and clinical
      isolates of C. pneumoniae, C. trachomatis and C. psittaci. PCR products were
      digested with restriction enzymes Alu I and Mbo I and separated by polyacrylamide
      gel electrophoresis. Restriction fragment patterns varied in length from 8-12
      bands of 30-400 bp in size in Alu I digests, and 6-7 bands of 50-400 bp in size
      in Mbo I digests. Strains representing different chlamydia species were easily
      distinguishable by this method, as were different serovars of C. trachomatis.
      Strains of C. pneumoniae tested include laboratory strain TW-183 and recent
      clinical isolates from Atlanta, Brooklyn, Wisconsin and Norway. One combination
      of primers reacted with C. psittaci strains and C. pneumoniae strain TW-183, but
      not with other strains of C. pneumoniae tested regardless of the concentration of
      DNA in the sample. With use of a pan-reactive primer combination, however,
      restriction patterns were similar in all strains of C. pneumoniae tested. This
      gene typing technique can be valuable for distinguishing the three chlamydial
      species and potentially strains of C. pneumoniae in clinical and epidemiologic
      studies.

PMID- 1361963
TI  - Identification of new world Leishmania using ribosomal gene spacer probes.
AB  - DNA probes from the nontranscribed ribosomal spacer (NTS), of Leishmania garnhami
      and Leishmania braziliensis were constructed and tested for sensitivity and
      specificity against different Leishmania isolates. The L. garnhami probes were
      species-specific under hybridization conditions of high stringency, but displayed
      specificity for the mexicana complex under conditions of intermediate stringency.
      The L. braziliensis probes showed 'complex' specificity. RFLP for the
      nontranscribed spacer within the braziliensis complex revealed very homogeneous
      patterns even for organisms currently accepted as different species. A PCR assay
      for the detection of Leishmania from the braziliensis complex is presented.

PMID- 1361964
TI  - Effects of growth hormone-releasing hormone and somatostatin on sleep EEG and
      nocturnal hormone secretion in male controls.
AB  - When applied centrally to animals, growth hormone-releasing hormone (GHRH)
      stimulates slow-wave sleep (SWS), whereas somatostatin (SRIF) increases REM
      sleep. We investigated whether these peptides also affect the sleep EEG in humans
      when given intravenously by comparing polysomnographically the effects of four
      boluses of (1) placebo, (2) 50 micrograms GHRH or (3) 50 micrograms SRIF
      administered at 22.00, 23.00, 24.00 and 1.00 h to 7 male controls. In addition,
      we collected blood samples through a long catheter every 20 min from 22.00 to
      7.00 h and measured plasma cortisol and growth hormone (GH) levels. In comparison
      with SRIF and placebo, GHRH produced a significant increase in plasma GH
      concentration throughout the night (mean +/- SD: 10.8 +/- 2.0 ng/ml after GHRH;
      3.0 +/- 1.7 ng/ml after SRIF and 3.2 +/- 2.0 ng/ml after placebo). SRIF failed to
      substantially attenuate the nocturnal GH release. Nocturnal cortisol secretion
      was blunted after GHRH but remained unaffected by SRIF (61.4 +/- 12.9 ng/ml after
      placebo; 46.6 +/- 19.7 ng/ml after GHRH and 70.8 +/- 12.6 ng/ml after SRIF).
      Quantitative sleep EEG staging showed a significant increase in SWS after GHRH
      administration but no change after SRIF (percent spent in SWS per night: 14.0 +/-
      5.6 after placebo, 20.2 +/- 6.6 after GHRH and 15.1 +/- 8.2 after SRIF).
      Application of SRIF was accompanied by a trend toward increased REM density. The
      effects of episodic GHRH administration upon SWS, GH and cortisol secretion were
      opposite to those previously reported for corticotropin-releasing hormone, which
      supports the view that neuroregulation of human sleep involves an interaction of
      central GHRH and corticotropin-releasing hormone.

PMID- 1361965
TI  - Are 5-HT receptors or beta-adrenoceptors involved in idazoxan-induced food and
      water intake?
AB  - Idazoxan (10 mg/kg, i.p.) produces an unexpected increase in food intake in
      freely-feeding rats which has been linked to its high affinity for non
      adrenoceptor idazoxan binding sites. In this study, a dose-related antagonism of
      idazoxan-induced food intake by the beta-adrenoceptor antagonist (-)-propranolol
      (5-20 mg/kg, i.p.), which also blocks 5-HT1 (5-hydroxytryptamine1) receptors has
      been demonstrated. (+)-Propranolol (10, 20 mg/kg, i.p.) did not attenuate
      idazoxan-induced feeding. (-)-Propranolol (10 mg/kg, i.p.) but not the (+)
      enantiomer (10 mg/kg, i.p.) also significantly inhibited the food intake, induced
      by the 5-HT1A agonist 8-OH-DPAT (0.25 mg/kg, i.p.). Idazoxan-induced feeding was
      not altered by the selective beta-adrenoceptor antagonists betaxolol (beta 1; 5
      mg/kg, i.p.) and ICI 118,551 (beta 2; 5 mg/kg, i.p.) but was potentiated by the 5
      HT receptor antagonist metergoline (5 mg/kg, i.p.). The anomalous findings with
      metergoline may reflect its action at different sub-types of 5-HT receptor. The
      water intake induced by idazoxan and the peripherally-active alpha 2-adrenoceptor
      antagonist L-659,066 was also blocked in a stereoselective manner by propranolol
      (10 mg/kg) but not significantly by either metergoline (5 mg/kg, i.p.), the beta
      1-adrenoceptor antagonist betaxolol (5 mg/kg, i.p.) nor by the beta 2
      adrenoceptor antagonist ICI 118,551 (5 mg/kg, i.p.). These results suggest that
      the food intake induced by idazoxan (and perhaps mediated by non-adrenoceptor
      idazoxan binding sites) may involve the 5-HT system, although further studies,
      using antagonists acting selectively at the different sub-types of 5-HT receptor,
      are required to confirm this.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361966
TI  - Effects of chronic treatment with ethanol and withdrawal of ethanol on levels of
      dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the striatum of
      the rat. Influence of benzodiazepines, barbiturate and somatostatin.
AB  - Administration of ethanol for 40 days, at 10.53 +/- 0.25 g/kg/day did not modify
      levels of dopamine (DA) or 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum
      of the rat; however, the concentration of homovanillic acid (HVA) and the ratio
      of turnover were increased in a statistically significant way (P < 0.05). Twenty
      four hours after withdrawal of ethanol appears as the central time of the ethanol
      induced abstinence syndrome, showing noticeable decreases in levels of DA (P <
      0.05) and DOPAC (P < 0.05), with respect to control and chronically ethanol
      treated groups. The concentrations of DA, DOPAC and HVA and ratio of turnover
      values showed a tendency to return to control normal levels of 48 hr after
      ethanol withdrawal, although the differences still showed statistical
      significance (P < 0.05). The intraperitoneal injection of saline, the water
      soluble benzodiazepine midazolam, the barbiturate thiopental and somatostatin, in
      single doses, resulted in a noticeable increase in levels of DA, DOPAC and HVA
      and ratio of turnover values. The intraperitoneal injection of midazolam produced
      statistically significant decreases in levels of DOPAC and ratio of turnover
      values (P < 0.01) in rats 48 hr after withdrawal of ethanol, with respect to
      control and chronically ethanol-treated animals, in contrast to the absence of
      changes produced when injecting thiopental or somatostatin.

PMID- 1361967
TI  - Characterization of glutamate efflux from preoptic area synaptosomes.
AB  - Treatment of ovariectomized rats in vivo with ovarian steroids has been found to
      influence the efflux of glutamate and gamma-aminobutyric acid from preoptic area
      synaptosomes incubated in vitro. Since these studies indicated a possible role of
      the glutamate carrier in steroid-modulated release of amino acids, the present
      studies examined the characteristics of efflux of glutamate and of the carrier
      system for glutamate in synaptosomes of the preoptic area derived from
      ovariectomized hormone-treated rats. The efflux of [3H]glutamate from preoptic
      area synaptosomes, was induced by glutamate and by the glutamate carrier agonist,
      D-aspartate; the putative glutamate carrier antagonist dihydrokainate failed to
      block this efflux. Dihydrokainate inhibited the uptake of glutamate but it was
      less effective than D-aspartate. The excitatory amino acid receptor agonists, N
      methyl-D-aspartate and kainate were without effect while quisqualate modestly
      stimulated the efflux of [3H]glutamate. Efflux of [3H]glutamate, induced by
      glutamate itself or by D-aspartate was not blocked by the excitatory amino acid
      receptor antagonists, D-2-amino-5-phosphonovaleric acid, 6,7-dinitroquinoxaline
      2,3-dione or kynurenate. Glutamate-induced efflux of [3H]glutamate did not
      require external Ca2+. Glutamate altered neither the basal nor the potassium
      induced increases in the intrasynaptosomal concentration of Ca2+ as measured by
      the fura-2 method. Glutamate-induced efflux of [3H]glutamate was blocked by the
      putative chloride channel antagonist, 4,4'-diisothiocyanatostilbene-2,2'
      disulfonic acid. It is concluded that the glutamate-induced efflux of
      [3H]glutamate in synaptosomes of the preoptic area is a carrier-mediated process
      that does not require activation of receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361968
TI  - Pattern recognition by matched filtering: an analysis of sleep spindle and K
      complex density under the influence of lormetazepam and zopiclone.
AB  - The evaluation of sleep EEG patterns is mostly accomplished by visual analysis.
      With modern personal computers however, it is possible to perform signal
      detection within a reasonable length of time automatically. This paper presents a
      method for signal processing based on matched filtering. This allows the
      detection of sleep spindles and K-complexes in a sleep EEG recording with a high
      degree of accuracy. First the technique is described, and the results of a
      validation study based on the comparison of visual evaluations and computer
      analysis are presented. Thereafter, results of an application study are
      presented. Sleep spindle and K-complex density under the influence of
      lormetazepam and zopiclone were examined. Under both medications sleep spindle
      density increased while K-complex density decreased. Computation of Pearson's
      correlation coefficients demonstrated that the interindividual sleep spindle and
      K-complex variations under both treatments are highly correlated. The data
      suggest that lormetazepam and zopiclone, although chemically different, have a
      similar mode of action and display comparable effects on the sleep EEG.

PMID- 1361969
TI  - Cerebrospinal-fluid neuropeptides: a biochemical subgrouping approach.
AB  - Cerebrospinal-fluid (CSF) corticotropin-releasing hormone, somatostatin, and
      thyrotropin-releasing hormone were measured by specific radioimmunoassays in 257
      hospitalized psychiatry patients suffering from dementia disorders (n = 85),
      schizophrenia (n = 104), and mood and anxiety disorders (n = 39). Neurological
      controls (n = 29) were also investigated. Since there were large overlaps of the
      peptide levels across the nosological groups we subjected the dataset to a three
      dimensional normal mixture distribution analysis. We obtained four biochemically
      separable clusters. Dementia disorders, but not the others, were heterogeneously
      distributed in these clusters but after eliminating the effects of age and
      illness duration this difference disappeared. No single clinical, psychological,
      or background variable emerged as a prominent correlate of the neuropeptide
      clusters. It is concluded that although CSF neuropeptide concentrations in
      psychiatric patient populations appear to be separable into distinct, normally
      distributed subgroups this distinction does not coincide with present nosological
      classifications.

PMID- 1361970
TI  - Effects of an oral glucose load on plasma neurotransmitters in humans:
      involvement of REM sleep?
AB  - Plasma noradrenaline (NA), adrenaline (Ad), dopamine (DA), platelet serotonin
      (p5HT), free serotonin (f5HT), glucose, heart rate (HR) and blood pressure (BP)
      were measured before and after an oral load of glucose (OGTT) in 100 normal
      humans. One sham-feeding test was performed in every subject 2-3 weeks before
      OGTT. Aside from glucose rise, significant increases in NA, p5HT and the NA/Ad
      ratio were registered. No significant changes were observed in Ad, DA, f5HT, HR
      and BP mean +/- SE values. Significant reductions in the NA/p5HT, Ad/p5HT and
      DA/p5HT ratios' mean values were registered at 90 and 180 min. Several
      significant correlations were found amongst plasma neurotransmitters. Very high
      positive correlations were obtained when NA, Ad and DA were plotted against the
      ratio of each one of them over p5HT; however, they (r = 0.99) decreased
      significantly at 90 and 180 min. Upon evaluation of these results we infer that
      quiescence of adrenal glands occurs during OGTT. Under such circumstances, plasma
      neurotransmitters are left under the control of a central bipolar system:
      noradrenergic-parasympathetic. All numerical data strongly suggest that the
      noradrenergic system predominates at 60, 120 and 210 min, whereas parasympathetic
      predominance occurs at 90 and 180 min. The fact that the latter is interfered by
      atropine reinforces this hypothesis. Analyses of correlations also suggest that
      DA and p5HT probably act as a buffer and modulate the excessive increase in NA
      plasma levels registered during OGTT.

PMID- 1361971
TI  - The influence of neuroleptics on specific syndromes and symptoms in
      schizophrenics with unfavourable long-term course. A 5-year follow-up study of 50
      chronic schizophrenics.
AB  - Fifty chronic schizophrenics with severe residual psychopathology were followed
      up over a 5-year period. All of them had continuously received neuroleptics for
      many years before and throughout the period of investigation. In 60% (n = 30) of
      the patients positive symptoms which were unchanged in quality and severity were
      present throughout the period of investigation. In 28% (n = 14) of the patients
      marked positive symptoms persisted from the very beginning up to 1990 (in every
      case more than 20 years). Applying Leonhard's classification it was obvious that
      syndromes are roughly unchanged with respect to the preneuroleptic era. In these
      patients neuroleptics seemed to have only unspecific suppressing effects on
      affectivity. It is supposed that in schizophrenia which leads to severe residual
      psychopathology, Leonhard's classification is superior to the positive-negative
      distinction and is a promising concept for future research in etiology and
      therapy.

PMID- 1361972
TI  - Quantitative EEG and autonomic patterns of synthetic peptides related to
      dermorphin.
AB  - The effects of dermorphin on EEG and autonomic variables are compared with the
      effects of 2 analogues and 2 homologues, all administered
      intracerebroventricularly in the rabbit. Dermorphin was the most effective in
      modifying all considered parameters: increase of cortically derived and
      calculated total power, bradycardia, respiratory depression and hypothermia. The
      dibenzylated heptapeptide was essentially inactive. The electrocortical pattern
      induced by the administration of L-dermorphin suggests a functional correlation
      between the amino acid D-ala 2 and the effects on EEG. Comparison between the
      effects produced by the N-terminal tetrapeptide and pentapeptide led us to
      hypothesize that amino acid Tyr 5 may be specifically involved in inducing the
      autonomic effects.

PMID- 1361974
TI  - Response of oligodendrocytes to glutamate and gamma-aminobutyric acid in the
      intact mouse optic nerve.
AB  - The electrophysiological response to glutamate and gamma-aminobutyric acid (GABA)
      is determined in oligodendrocytes of the isolated intact mouse optic nerve,
      identified by their characteristic morphology following iontophoretic injection
      with horseradish peroxidase (HRP). In this study, mature myelin-forming
      oligodendrocytes are shown for the first time to respond to glutamate and GABA in
      situ, by a 2-3 mV depolarization. Morphologically homogeneous oligodendrocytes
      exhibit a heterogeneous response to glutamate and GABA; some cells respond to
      both excitatory amino acids, whereas others respond to one but not the other, and
      some oligodendrocytes do not respond to either. Oligodendrocytes uniformly
      depolarize in elevated [K+]o and it is concluded that the effect of glutamate and
      GABA is not mediated by an increase in [K+]o released from axons or astrocytes.
      The oligodendrocyte response to amino acids may be important in axon-to
      oligodendrocyte signalling at the nodes of Ranvier.

PMID- 1361973
TI  - Comparative study on the behavioral and EEG changes induced by diazepam,
      buspirone and a novel anxioselective anxiolytic, DN-2327, in the cat.
AB  - Behavioral and EEG effects of 2-(7-chloro-1,8-naphthyridin-2-yl)-3-[(1,4)-dioxa-8
      (azas piro-[4.5]dec-8- yl)carbonylmethyl]isoindolin-1-one (DN-2327; 1, 5 and 20
      mg/kg p.o.) were compared to those of diazepam (0.2 and 1 mg/kg p.o.) and
      buspirone (1 and 5 mg/kg p.o.) in freely moving cats. DN-2327 did not affect
      motor coordination or the relative percentages of the three sleep-wakefulness
      stages. Diazepam (1 mg/kg) increased wakefulness and non-REM sleep, and buspirone
      (5 mg/kg) also increased wakefulness and decreased REM sleep. In addition,
      diazepam (1 mg/kg) caused severe motor disturbance, but buspirone did not. The
      cortical EEG power density spectra during wakefulness were changed almost dose
      dependently by DN-2327 (decreased: 2-7.75 Hz; increased: 20-49.75 Hz), and dose
      dependently by diazepam (decreased: 2-7.75 Hz; increased 13-49.75 Hz) and
      buspirone (decreased: 4-9.75 and 13-19.75 Hz). The effect of DN-2327 on the
      cortical EEG varied with the sleep-wakefulness stage. The power of the 4- to 7.75
      Hz frequency (theta) band of the hippocampal EEG during wakefulness was decreased
      by diazepam and buspirone but not by DN-2327, while the peak frequency of its
      spectra was decreased only by diazepam. On the other hand, during non-REM sleep,
      DN-2327 decreased the power of the theta band as did diazepam. These results
      indicate that the behavioral and EEG effects of DN-2327 differ completely from
      those of buspirone and considerably from those of diazepam and that the EEG
      effect of DN-2327 varies with the sleep-wakefulness stage.

PMID- 1361975
TI  - Potency of depolarization-induced transmitter release is determined by divalent
      cation influx in PC 12 cells.
AB  - Evoked release of [3H]dopamine ([3H]DA) from pheochromocytoma cells (PC 12) is
      dependent on extracellular calcium ([Ca2+]ex), but it can take place if calcium
      ions (Ca2+) are substituted by other divalent ions such as strontium (Sr2+) and
      barium (Ba2+). The potency of the divalent cations at supporting release varies
      with the cell type; in PC 12 cells the order of potency is Ba2+ > Sr2+ > Ca2+.
      The close correlation between depolarization-evoked Ca2+ entry and depolarization
      evoked transmitter release prompted us to examine whether the higher evoked
      transmitter release in the presence of Sr2+ correlates with an increased evoked
      Sr2+ influx. Influx studies were conducted on PC12 cells using a radioactive
      tracer (45Ca2+ or 85Sr2+, < 1 microM) in the presence of either Sr2+ (0.5 mM) or
      Ca2+ (0.5 mM). Depolarization with K Cl (60 mM) increased evoked 45Ca2+ influx 2
      fold when Ca2+ was substituted with Sr2+. Similarly, evoked 85Sr2+ influx
      increased 1.87-fold by substituting Ca2+ for Sr2+. Thus the amount of evoked
      cation influx is determined by the type of divalent ion which is accessible in
      the extracellular medium, independently of the radioactive tracer used. Increased
      evoked transmitter release in the presence of Sr2+ was associated with increased
      evoked Sr2+ influx. This suggests that the potency of evoked transmitter release
      is determined predominantly by the influx of divalent cations. Furthermore, the
      steps subsequent to cation influx in the release process are equally efficient
      for both cations.

PMID- 1361976
TI  - The degeneration of the excitatory climbing fibers enhances [3H]MK-801 and
      [3H]CGP 39653 binding sites in the rat cerebellar cortex.
AB  - The effect of a single injection of 3-acetylpyridine (3-AP), which led to a
      degeneration of the excitatory cerebellar climbing fibers, was studied on the
      binding of [3H]MK-801, a non-competitive NMDA antagonist, in the rat cerebellar
      cortex. The same treatment increased also the binding of [3H]CGP 39653, a new
      NMDA competitive antagonist. Saturation isotherms showed a significant increase
      of the maximal number of binding sites (Bmax) for [3H]CGP 39653 and [3H]MK-801
      (+48 and 36% respectively) with no change in the affinity 4-9 days after the
      administration of 3-AP. Our data demonstrate that in the cerebellar cortex both
      NMDA recognition site labelled by [3H]CGP 39653 and its modulatory site labelled
      by [3H]MK-801 may undergo plastic changes when the glutamatergic receptors and
      transmission are denervated.

PMID- 1361978
TI  - Reduction of somatostatin receptors in rat hippocampus by treatment with 5,7
      dihydroxytryptamine.
AB  - Several lines of evidence suggest that somatostatin (SS) may interact with
      serotonergic neurons in the central nervous system. To assess whether SS acts
      presynaptically on serotonin (5-hydroxytryptamine, (5-HT)) neurons, SS receptors
      were measured in membranes from the hippocampus, a brain region that receives
      dense serotonergic innervation and has a high number of SS receptors in control
      and 5,7-dihydroxytryptamine (5,7-DHT)-treated rats, at 1 and 3 weeks after
      injection. Intracerebroventricular (i.c.v.) injection of the 5-HT-specific
      neurotoxin 5,7-DHT (11 micrograms (free base) dissolved in 10 microliters of
      isotonic saline containing 0.01% ascorbic acid) produced a 70% reduction in
      hippocampal 5-HT content at 3 weeks after injection but not at 1 week. This
      change was associated with a significant decrease in SS receptor density in rat
      hippocampus only at 3 weeks following the injection, without influencing the
      apparent affinity of the receptors at any time. Administration of 5,7-DHT did not
      affect somatostatin-like immunoreactivity (SSLI) levels at both times studied.
      These results suggest that some of the hippocampal SS receptors may be localized
      presynaptically on the serotonergic nerve terminals.

PMID- 1361977
TI  - Dopaminergic neurons in the cat dorsal motor nucleus of the vagus, demonstrated
      by dopamine, AADC and TH immunohistochemistry.
AB  - In the rostral part of the dorsal motor nucleus of the vagus of the cat, neurons
      do not contain histochemically detectable catecholamines, even though many
      perikarya contain both intense aromatic L-amino acid decarboxylase (AADC)
      immunoreactivity and strong monoamine oxidase enzymatic activity. Similarly
      located perikarya have distinct immunoreactivities to tyrosine hydroxylase (TH)
      and dopamine after treatment with colchicine. Since inhibition of monoamine
      oxidase fails to reveal dopamine in these cells, its absence in non-colchicine
      treated animals cannot be due to rapid deamination. It appears that dopamine is
      synthesized by TH and AADC in dorsal motor vagal cells and is then rapidly
      transported from the perikarya.

PMID- 1361979
TI  - ACTH1-39 inputs to mesocorticolimbic dopaminergic neurons: light and electron
      microscopic examination.
AB  - Single- and double-labeling immunocytochemical staining procedures were used to
      examine the relationship between adrenocorticotropin (ACTH)-containing nerve
      terminals and dopaminergic (DA) neurons in the rat midbrain, using both light and
      electron microscopy. At the light microscopic level, ACTH neuronal processes were
      found largely in restricted regions occupied by the mesolimbic and mesocortical
      DA neurons. At the electron microscopic level, in the central linear nucleus,
      ACTH axon terminals made symmetric and asymmetric synaptic contacts with DA
      dendrites, as well as appositions with unlabeled axon terminals which, in turn,
      synapsed upon DA dendrites. These data suggest that ACTH functions as a
      neurotransmitter/neuromodulator in the brain, and such ACTH-DA synapses may be
      important for stress-induced changes in mesocorticolimbic DA neuronal activity.

PMID- 1361980
TI  - Regulation of dopaminergic activity, but not tyrosine hydroxylase, is diminished
      after chronic inorganic lead exposure.
AB  - Previous work has indicated that the neurotoxic action of environmentally
      relevant levels of lead (Pb) on dopaminergic neurons is primarily presynaptic in
      nature and related to impaired regulation of dopamine (DA) synthesis and
      decreased DA release. This study was conducted to assess the functional integrity
      of the regulation of DA synthesis in caudate-putamen (C-P) and nucleus accumbens
      (NAc) of chronically Pb-exposed rats by measuring tyrosine hydroxylase (TH)
      activity. A pharmacological paradigm was employed that isolated autoreceptor
      mediated regulation of the enzyme. At parturition dams received 0.2% Pb acetate
      (1090 ppm) in the drinking water while control dams received distilled water.
      Offspring were weaned to and maintained on the same solution given their dams
      until termination at 60 or 120 days. Rats were given saline or one of three DA
      agonists (EMD 23448, CGS 15855A, TL-99) 45 or 60 min before termination followed
      15 min later by 750 mg/kg i.p. of gamma-butyrolactone (GBL) or saline. The
      ability of a DA agonist to prevent the GBL-induced increase in DA content was
      significantly altered in C-P of exposed rats compared to controls. No effect of
      Pb on DA content was observed in NAc. Furthermore, no differences in the ability
      of DA agonists to inhibit GBL-induced activation of TH in Pb-exposed compared to
      control animals were apparent in either brain region at either age by use of the
      tritium release method or the accumulation of L-DOPA. On the other hand,
      concentrations of DA metabolites in exposed rats given GBL and EMD 23448 were
      significantly lower than those in controls in both C-P and NAc. These findings
      support previous work suggesting that chronic Pb has multiple actions on CNS
      dopaminergic neurons consisting of impaired regulation of DA content and
      decreased DA release. However, these effects cannot be attributed to alterations
      in autoreceptor-mediated regulation of TH activity.

PMID- 1361981
TI  - PFGE-resolved RFLP analysis and long range restriction mapping of the DNA of
      Arabidopsis thaliana using whole YAC clones as probes.
AB  - The cleavage patterns of 23 rare-cutting restriction endonucleases (rcREs) on
      high molecular weight DNA, isolated from leaves of Arabidopsis thaliana
      (Arabidopsis), have been analysed using pulsed field gel electrophoresis (PFGE).
      The DNA digested with rcREs can be used for restriction fragment length
      polymorphism (RFLP) analysis. We show that RFLPs are more readily identified in
      restriction fragments that require resolution by PFGE than in smaller restriction
      fragments. Taking advantage of the low dispersed repetitive DNA content of the
      Arabidopsis genome, whole yeast artificial chromosomes (YACs) were used as probes
      to PFGE resolved genomic DNA. This enabled whole YAC clones to be used as RFLP
      markers and long range restriction maps to be constructed. These techniques
      should enhance the analysis of regions of the genome of Arabidopsis (and other
      organisms with low levels of dispersed repetitive DNA) that are the subject of
      chromosome walking strategies to isolate particular loci.

PMID- 1361982
TI  - PCR-based RFLP analysis of DNA sequence diversity in the gastric pathogen
      Helicobacter pylori.
AB  - DNA sequence diversity among 60 independent isolates of the gastric pathogen
      Helicobacter pylori was assessed by testing for restriction fragment length
      polymorphisms (RFLPs) in several PCR-amplified gene segments. 18 Mbol and 27
      HaeIII RFLPs were found in the 2.4 kb ureA-ureB (urease) segment from the 60
      strains; this identified 44 separate groups, with each group containing one to
      four isolates. With one exception, each isolate not distinguished from the others
      by RFLPs in ureA-ureB was distinguished by Mbol digestion of the neighboring 1.7
      kb ureC-ureD segment. The 1.5 kb flaA (flagellin) gene, which is not close to ure
      gene cluster, was also highly polymorphic. In contrast, isolates from initial and
      followup biopsies yielded identical restriction patterns in each of the three
      cases tested. The potential of this method for detecting population heterogeneity
      was tested by mixing DNAs from different strains before amplification: the arrays
      of restriction fragments obtained indicated co-amplification from both genomes in
      each of the five pairwise combinations tested. These results show that H. pylori
      is a very diverse species, that indicate PCR-based RFLP tests are almost as
      sensitive as arbitrary primer PCR (RAPD) tests, and suggest that such RFLP tests
      will be useful for direct analysis of H. pylori in biopsy and gastric juice
      specimens.

PMID- 1361983
TI  - [Role of histamine H1 receptor antagonists (antihistaminics) in therapy of
      bronchial asthma].

PMID- 1361984
TI  - Modulation of swimming rhythmicity by 5-hydroxytryptamine during post-embryonic
      development in Xenopus laevis.
AB  - During the first 24 h of post-embryonic development in Xenopus laevis, a rapid
      change in the neural activity underlying swimming occurs in which the duration of
      ventral root discharge on each cycle increases from a single compound impulse to
      discrete bursts of activity. Moreover, this change in motor output progresses
      rostrocaudally, suggesting that it could result from the influence of a
      descending neural pathway upon the spinal rhythm-generating circuitry during
      early post-embryonic development. To begin to examine whether serotonergic
      neurons of brainstem raphe nuclei might have a role in this swimming development,
      we have studied the effects of 5-hydroxytryptamine (5HT) on fictive swimming in
      embryonic and larval animals. As previously demonstrated for other vertebrate
      locomotor rhythms, we find that bath-applied 5HT enhances the duration of motor
      activity on each cycle of larval fictive swimming. In addition, our results show
      that the sensitivity of the swimming rhythm to exogenous 5HT follows a strict
      rostrocaudal gradient. In young embryos (stages 32-36) 5HT does not affect the
      duration of ventral root impulses per cycle; by the time of hatching (stage
      37/38), rostral but not caudal discharge is enhanced, and by stage 42 (24 h post
      hatching) 5HT can increase motor burst durations along most of the length of the
      animal. These reversible changes induced by bath-applied 5HT closely resemble the
      normal rostrocaudal development of burst discharge during swimming in animals
      some 12 h older.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1361985
TI  - Closure of potassium M-channels by muscarinic acetylcholine-receptor stimulants
      requires a diffusible messenger.
AB  - The M-current (IK(M)) is a slow voltage-gated K+ current which can be inhibited
      by muscarinic acetylcholine-receptor (mAChR) agonists. In the present experiments
      we have tested whether this inhibition results from a local (membrane-delimited)
      interaction between the receptor and adjacent channels, or whether channel
      closure is mediated by a diffusible messenger. To do this, single KM(+)-channel
      currents were recorded from membrane patches in dissociated rat superior cervical
      sympathetic neurons by using cell-attached patch electrodes. Channel activity was
      inhibited when muscarine was applied to the cell membrane outside the patch but
      persisted when channels were exposed to muscarine added to the pipette solution.
      We conclude that a diffusible molecule (or molecules) is (are) required to induce
      intrapatch channel closure following activation of extra-patch receptors.

PMID- 1361986
TI  - Electrophysiological characterization of a TTX-sensitive sodium current in native
      Xenopus oocytes.
AB  - We have studied a fast inward current expressed in oocytes from one Xenopus
      laevis. This current was characterized as a sodium current. It was activated by
      depolarizations to -50 mV or higher, peaked within 3-5 ms, and then decayed
      following a mono-exponential timecourse. When clamped at different holding
      potentials, the current displayed voltage-dependent inactivation with a V0.5 of 
      51 mV. The channel responsible for this Na+ entry was blocked by tetrodotoxin
      with a K0.5 of 8 nM, and was resistant to block by lidocaine at concentrations up
      to 100 microM. The pharmacological similarities between neuronal and oocyte
      sodium channels suggest that the two channels share a conserved structure.

PMID- 1361987
TI  - Wolbachia endosymbionts responsible for various alterations of sexuality in
      arthropods.
AB  - Rickettsia-like maternally inherited bacteria have been shown to be involved in a
      variety of alterations of arthropod sexuality, such as female-biased sex ratios,
      parthenogenesis, and sterility of crosses either between infected males and
      uninfected females or between infected individuals (cytoplasmic incompatibility).
      We have characterized several of these microorganisms through partial sequences
      of the small (16S) and large (23S) subunit ribosomal DNA. All the symbionts
      identified, which include several cytoplasmic incompatibility microorganisms,
      several endosymbionts of terrestrial isopods, and symbionts of two thelytokous
      Trichogramma wasp species, belong to a monophyletic group of related symbionts,
      some of which have previously been detected in several insects exhibiting
      cytoplasmic incompatibility. Three molecular lineages can be identified on the
      basis of 16S as well as 23S sequences. Although they are only known as
      endocellular symbionts, Wolbachia spread by horizontal transfer across host
      lineages as evidenced by their diversification which occurred long after that of
      their hosts, and by the non-congruence of the phylogenetic relationships of
      symbionts and their hosts. Indeed, symbionts of two different lineages have been
      found in the same host species, whereas closely related endosymbionts are found
      in distinct insect orders. Isopod endosymbionts form a separate lineage, and they
      can determine feminization as well as cytoplasmic incompatibility. The ability to
      determine cytoplasmic incompatibility, found in all lineages, is probably
      ancestral to this group.

PMID- 1361989
TI  - Effects of LY163502, a D2 dopaminergic agonist, on the sexual behavior of male
      rats.
AB  - LY163502, a selective D2 receptor agonist, has been reported to stimulate sexual
      behavior in both copulating and noncopulating male rats. Three experiments were
      conducted to further characterize the role of dopamine on male sexual behavior.
      In the first experiment, quinelorane (LY163502) was directly infused into the
      medial preoptic area (MPOA) of castrated males either alone or in combination
      with subphysiological levels of testosterone (T) exposure. The results showed
      that male sexual behavior was not affected by infusion of LY163502 alone,
      subphysiological T levels alone, or the combination of LY163502 and
      subphysiological T levels. For the second experiment, all animals received
      physiological levels of T and MPOA infusions of LY163502 or saline. The results
      showed an earlier restoration of male sexual behavior in the LY163502 group when
      compared to the T-only group. In the third study, noncopulating, gonadally intact
      males received SC injections of either LY163502 or saline 30 min prior to
      copulatory testing. The results showed that LY163502 induced a significant
      decrease in mount and intromission latencies after 14 days of drug exposure. From
      these results, we conclude a) that D2 receptors play a role in the facilitation
      of male sexual behavior and b) that the action of dopamine at D2 receptors
      requires the presence of T.

PMID- 1361988
TI  - Psychostimulant-induced activity is attenuated by two putative dopamine release
      inhibitors.
AB  - Centrally administered amphetamine (AMPH), cathinone, (CATH), or cocaine (COC)
      have each been shown to produce elevated activity in rats and this effect is dose
      responsive. The question remains whether these psychostimulants share a common
      mechanism of action (i.e., do these psychostimulants act by releasing dopamine to
      increase activity levels?). Experiments were, therefore, conducted to measure the
      spontaneous activity of these three centrally administered psychostimulants in
      rats following pretreatment with two putative dopamine release inhibitors, viz.,
      5-(4-methyl-1 piperazinyl)imidazol(2,1-b) (1,3,5)-benzothiadiazepine maleate [CGS
      10746B (CGS); 20 mg/kg)] and 4-(4-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5
      pyridinedicar boxylic acid methyl 1-methyl-ethyl ester [isradipine (ISR); 2.5
      mg/kg)]. Rats fitted with chronic indwelling ventricular cannulae received a
      single dose of ICV-administered CATH (32 micrograms), AMPH (16 micrograms), COC
      (100 micrograms), or vehicle. Selection of these ICV doses of stimulant drugs was
      based upon results obtained in preliminary studies that indicated similar
      elevations of activity. ICV administration of each of these drugs/doses was
      preceded (20 min) by peripherally administered CGS, ISR, or vehicle. Results show
      that ICV CATH (32 micrograms), AMPH (16 micrograms), COC (100 micrograms)
      equieffectively elevate activity (two- to threefold) and that, in each case, this
      increase was significantly attenuated by pretreatment with CGS or ISR.

PMID- 1361990
TI  - Further studies on N-methyl-1(3,4-methylenedioxyphenyl)-2-aminopropane as a
      discriminative stimulus: antagonism by 5-hydroxytryptamine3 antagonists.
AB  - Using a standard two-lever operant paradigm, male Sprague-Dawley rats were
      trained to discriminate 1.5 mg/kg N-methyl-1(3,4-methylenedioxyphenyl)-2-
      aminopropane (MDMA) from saline using a variable-interval 15-s schedule of
      reinforcement for food reward. Tests of stimulus antagonism were conducted to
      further define the mechanism of action of MDMA as a discriminative stimulus. Low
      doses of the 5-hydroxytryptamine1A (5-HT1A) antagonist NAN-190, the 5-HT2
      antagonist pirenperone, and the dopamine antagonist haloperidol were able to
      somewhat attenuate the MDMA stimulus; however, none of these agents decreased
      MDMA-appropriate responding to less than 46%. The 5-HT3 antagonists zacopride and
      LY 278584 (ID50 = 0.02 micrograms/kg) antagonized the MDMA discriminative
      stimulus. Zacopride also attenuated the stimulus effects of 1-(2,5-dimethoxy-4
      methylphenyl)-2-aminopropane (DOM) in DOM-trained animals but not those of
      (+)amphetamine in (+)amphetamine-trained animals. Several possible mechanistic
      interpretations are provided but it is concluded that MDMA produces its stimulus
      effects via a complex mechanism involving both dopaminergic and serotonergic
      components.

PMID- 1361991
TI  - Comparison of the hyperhydrating effects of angiotensin II and isoproterenol.
AB  - Administration of a single dose of angiotensin II (AII) has been shown to induce
      a state of hyperhydration in rats that can last from 6-10 h depending upon the
      route of administration and the dose. The objective of the present study was to
      determine whether another dipsogenic agent, isoproterenol (ISO), a beta
      adrenoceptor agonist, could also induce a state of hyperhydration. The results
      indicate that a single SC dose of ISO can induce a hyperhydration that lasts from
      4-6 h depending upon the dose administered. Administration of graded doses of
      either AII or ISO induced graded increases both in the time of hyperhydration and
      change in accumulative mean fluid exchange, (delta FE, fluid exchange of treated
      less fluid exchange of control). These two parameters were related linearly and
      directly for each drug, although the slopes, but not the intercepts, of the
      relationship for each drug differed significantly. Because the objective of
      optimal hyperhydration should be to achieve the longest duration of positive
      fluid balance with the least amount of ingested fluid (i.e., delta FE), the
      slopes of the two lines provide a convenient way to compare the hyperhydration
      induced by AII and ISO. By this criterion, it would appear that AII provides a
      more optimal hyperhydration than ISO.

PMID- 1361992
TI  - Effect of mu-, kappa-, and delta-selective opioid agonists on thermoregulation in
      the rat.
AB  - The effect of selective mu-, kappa-, and delta-agonists on brain surface
      temperature (Tb), oxygen consumption (Vo2), and heat exchange (Q) was studied in
      unrestrained, male Sprague-Dawley rats using whole-body calorimetry.
      Hyperthermia, produced by PL-017 (1.86 nM) given ICV, resulted from increased Vo2
      and reduced Q during the first 15-45 min postinjection. Tb returned to control
      levels due to a combination of increased Q and reduced Vo2. PL-017-induced
      hyperthermia was abolished by the mu-selective antagonist CTAP (0.75 nM).
      Dynorphin A1-17 (4.65 nM), a kappa-selective agonist, reduced both Vo2 and Q,
      resulting in hypothermia that was blocked by the kappa-selective antagonist nor
      binaltorphimine (25 nM). The delta-selective agonist DPDPE (4.64 nM) caused no
      significant changes in Tb, Vo2, or Q. The data indicate that central stimulation
      of the mu- and kappa-opioid receptors affects both oxidative metabolism and heat
      exchange, which result in a change in Tb. These alterations can be prevented with
      selective opioid antagonist pretreatment.

PMID- 1361993
TI  - Constriction of environmental space and the behavioral response to the dopamine
      agonist quinpirole.
AB  - The present study examines the influence of size of testing environment on the
      behavioral profile seen following injection of the dopamine D2 receptor agonist
      quinpirole (0.5 mg/kg, n = 16) or saline (n = 16). All rats were tested in a
      counterbalanced order in both a small and large environment. Oral (licking)
      behaviors were observed exclusively in the small environment and only in drug
      treated rats; moreover, quinpirole increased rearing in the small but not large
      environment. Other behaviors--sniffing, face and body grooming--were affected by
      quinpirole but not in an environment-dependent manner. It is concluded that
      limiting environmental space promotes emergence of oral responding under
      quinpirole. The self-directed nature of this licking (paw- and tail-licking) may
      reflect a hierarchical transformation of quinpirole-induced hyperactivity from
      exploration of space to investigation of body parts.

PMID- 1361994
TI  - Oxytocin blocks the environmentally conditioned compensatory response present
      after tolerance to ethanol-induced hypothermia in mice.
AB  - The present study tested the hypothesis that the attenuation by oxytocin of
      tolerance to ethanol-induced hypothermia relies upon an impairment of the
      putative conditioning processes underlying environment-specific tolerance.
      According to the conditioning model of tolerance, such tolerance occurs because
      an opposite compensatory response conditioned to ethanol-paired cues attenuates
      ethanol's effects. Tolerance to ethanol-induced hypothermia was established to a
      particular environment over 4 days by injecting mice (daily) with oxytocin 2 h
      before ethanol, outside the colony room. As controls, other mice were injected
      similarly but following testing in the animal room. We found that oxytocin
      suppressed the conditioned compensatory response, revealed by injecting saline to
      every group in the tolerance-associated environment. These results suggest that
      oxytocin acted, at least partly, via an inhibition of the associative learning
      processes that facilitate tolerance development.

PMID- 1361995
TI  - Role of adrenergic neuronal activity in the yawning induced by tacrine and NIK
      247 in rats.
AB  - The present experiments were performed to investigate the potential role of
      central adrenergic neurons in regulating occurrence of yawning in rats.
      Intraperitoneal injection of tacrine (THA) or 9-amino-2,3,5,6,7,8-hexahydro-1H
      cyclopenta(b)-quinoline monohydrate HCl (NIK-247), cholinesterase inhibitors,
      induced yawning, which was markedly increased by pretreatment with the beta
      adrenoceptor antagonist, pindolol. The yawning evoked by tacrine or NIK-247 given
      alone or in combination with pindolol was inhibited by pretreatment with
      scopolamine but not by mecamylamine or spiperone. Treatment with tacrine or NIK
      247 increased acetylcholine content of the striatum, but this effect was not
      enhanced by pindolol, which per se did not affect basal acetylcholine content.
      Moreover, pretreatment with the central adrenaline synthesis inhibitors, (+-)-2,3
      dichloro-alpha-methylbenzylamine HCl (LY-78335) and 2-cyclooctyl-2
      hydroxyethylamine HCl (UK-1187A), increased tacrine-induced yawning. Subcutaneous
      injection of talipexole (B-HT 920), a dopamine D2 receptor agonist, evoked
      yawning, which was also increased by pindolol, LY-78335, and UK-1187A. These
      receptors antagonists and synthesis inhibitors per se did not cause yawning
      responses. The results suggest that the beta-adrenoceptor blockade and the
      inhibition of adrenaline synthesis facilitate the occurrence of yawning induced
      by cholinergic and dopaminergic agonists, and thus the central adrenergic
      neuronal systems may be implicated in the regulation of yawning responses.

PMID- 1361996
TI  - Hyperthermia induced by the dopamine D1 receptor agonist SK&F38393 in combination
      with the dopamine D2 receptor agonist talipexole in the rat.
AB  - The present experiments were performed to investigate the effects of dopamine D1
      receptor agonists given alone or in combination with dopamine D2 receptor
      agonists on body temperature in rats. The selective dopamine D1 receptor agonist,
      1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SK&F38393), produced
      hyperthermia. However, the dopamine D2 receptor agonist, B-HT 920 (talipexole),
      and the newly synthesized dopamine D2 receptor agonist, (S)-2-amino-4,5,6,7
      tetrahydro-6-propylamino-benzothiazole (SND 919), did not change the temperature.
      Interestingly, the SK&F38393-induced hyperthermia was enhanced by talipexole and
      SND 919. The drastic hyperthermia induced by combined administration of dopamine
      D1 and D2 receptor agonists was blocked by either the dopamine D1 receptor
      antagonist, SCH23390, or the dopamine D2 receptor antagonist, spiperone. On the
      other hand, treatment with prazosin, yohimbine, propranolol, scopolamine, or
      methysergide failed to affect the marked hyperthermia. The present results
      suggest that a functional link between dopamine D1 and D2 receptors may be
      synergistic in the regulation of body temperature and that concurrent stimulation
      of both dopamine D1 and D2 receptors thereby produces marked hyperthermia in the
      rat.

PMID- 1361999
TI  - Developments in antihistamines (H1).

PMID- 1362000
TI  - Centrally acting dopamine D2 receptor ligands: agonists.
AB  - The collected amount of research on D2 agonists is immense. The D2 research field
      has been, and still is, very dynamic. Despite this fact, only a few compounds
      have reached the clinic so far. At present there are clinical trials ongoing with
      partial D2 agonists possessing a range of intrinsic efficacies. Some of these
      agonists are tested for their potential effects in Parkinson's disease (high
      intrinsic efficacy), while others are tested for potential anti-psychotic effects
      (low intrinsic efficacy). An interesting possibility has arisen through the
      research on the synergism between D1 and D2 receptors. This could possibly be
      utilized in the alleviation of Parkinsonian symptomatology. The near future will
      show whether the compounds under evaluation hold promise for being new, valuable
      medicines for treating major diseases like Parkinson's disease and schizophrenia.

PMID- 1361997
TI  - Theoretical and therapeutic considerations for the anxiety disorders.
AB  - Everyone is familiar with that paralyzing state of dread known as anxiety.
      Although it is unpleasant, the experience of anxiety has adaptive aspects: it can
      serve as an impetus to effect beneficial life change and can facilitate
      psychological development. Anxiety becomes of clinical concern, however, when it
      interferes with intellectual function, or arrests normal social or vocational
      pursuits. Anxiety disorders are chronic illnesses. Treatment can eliminate many
      of the disease's debilitating features, but the underlying disorder is not
      usually cured. Discontinuation of treatment-pharmacological, behavioral, or both
      often results in the recurrence of symptoms. The focus of treatment, therefore,
      generally centers on striking a balance between the goal of alleviating the
      patient's symptoms, and the need to avoid the deleterious effects which result
      from long-term treatment (1). The intention of this paper is to review
      theoretical and therapeutic considerations for four types of anxiety disorder:
      panic disorder, generalized anxiety disorder, social phobia, and obsessive
      compulsive disorder. In doing this, emphasis will be placed on the physiological
      concomitants and, when possible, neuropsychological bases of these illnesses.
      Furthermore, pharmacological treatment will be related to the underlying
      substrata of the disorder whenever possible.

PMID- 1361998
TI  - Management of psychopharmacologic agents in children and adolescents.

PMID- 1362001
TI  - Pituitary adenylate cyclase activating polypeptide stimulates gallbladder
      motility in conscious dogs.
AB  - We investigated whether pituitary adenylate cyclase activating polypeptide (PA
      CAP27 and PACAP38) had any effect on gallbladder motility in conscious dogs, in
      which force transducers were chronically implanted in the gastric antrum,
      duodenum and gallbladder. PACAP27 and PACAP38 were administered intravenously
      during the digestive and interdigestive states at doses of 30, 100 and 300
      pmol/kg. By way of comparison, cholecystokinin octapeptide (CCK-OP) was
      administrated at doses of 3, 9 and 27 pmol/kg. As a result, each peptide evoked
      transient and tonic contractions both in the digestive and interdigestive states,
      and the effect on the motor index was dose dependent. PACAP27 and PACAP38 were
      0.11 +/- 0.03 and 0.04 +/- 0.01 as potent as CCK-OP in the digestive state, and
      0.18 +/- 0.04 and 0.02 +/- 0.01 in the interdigestive state, respectively, on a
      molar basis. Although PACAP27 and PACAP38 belong to the vasoactive intestinal
      polypeptide (VIP) family, intravenous administration of 300 pmol/kg of VIP had no
      effect on interdigestive gallbladder motility, but on the other hand inhibited
      gallbladder motility in the digestive state. The contractile effects of PACAP27
      and PACAP38 were almost completely abolished by pretreatment with atropine or
      hexamethonium, but not with L364718. An in vitro study using canine gallbladder
      strips showed that PACAP27 and PACAP38 had no effect on spontaneous gallbladder
      motor activity evoked by electric field stimulation, CCK-OP or acetylcholine. It
      was concluded that PACAP27 and PACAP38 stimulate gallbladder motility in
      conscious dogs through a preganglionic cholinergic mechanism.

PMID- 1362002
TI  - Genome structure of spirochetes.
AB  - The genome structures of several pathogenic spirochetes have recently been
      determined. The genomes of Borrelia species consist of a linear chromosome of
      approximately one million base pairs (Mb) and various linear and circular
      plasmids. Analysis of restriction fragment length polymorphisms and 16S ribosomal
      RNA sequence data indicate the division of Borrelia burgdorferi into at least
      three distinct genetic groups. Leptospira interrogans has a circular chromosome 5
      Mb in size and a 0.35 Mb extrachromosomal element. Repetitive sequence elements
      similar to insertion sequences have been identified in the Leptospira interrogans
      genome. The chromosome of Treponema pallidum subsp. pallidum is circular and has
      a size of approximately one Mb. Genetic studies conducted to date indicate that
      B. burgdorferi and L. interrogans have a high degree of genetic diversity,
      whereas remarkably few genetic differences have been observed among the
      pathogenic Treponema. Knowledge of the genomic structure of these organisms will
      serve as a basis for future genetic studies.

PMID- 1362003
TI  - A comparison of peripheral and central effects of clonidine on rat intestinal
      transit.
AB  - This study was designed to examine the effects of centrally or peripherally
      administered clonidine on small intestinal transit (SIT) in rats with diarrhea.
      Adult, male rats weighing 200 to 250 grams were surgically implanted with a
      silicone catheter in the proximal small intestine. Some animals were additionally
      implanted with a cannula in the right lateral cerebroventricle. SIT was
      determined by measuring the progression of an intraduodenally administered
      radioactive marker (Na2CrO4, 0.5uCi) along the small intestine. In most
      experiments, the effects of clonidine or saline were determined in animals
      challenged with sodium ricinoleate (100 mg) intraduodenally, the active
      ingredient in castor oil except treatment with reserpine. Given subcutaneously
      (s.c.) clonidine significantly inhibited SIT at doses between 25 and 200
      micrograms/kg. The effects of s.c. clonidine were antagonized by yohimbine, but
      not by reserpine or subdiaphragmatic truncal vagotomy. In contrast, given
      intracerebroventricularly (i.c.v.) clonidine produced a more long lasting effect
      at total doses greater than 20 micrograms. Intestinal antipropulsive effects of
      i.c.v. clonidine were blocked by yohimbine, but not by prazosin. Reserpine (s.c.)
      or 6-hydroxydopamine (i.c.v.) did not affect the actions of central clonidine.
      However, effects of i.c.v. clonidine were abolished after vagotomy. The results
      indicate that clonidine inhibits rat intestinal transit in similar total doses
      when given s.c. or i.c.v. Inhibition of SIT by clonidine results from alpha-2
      adrenergic receptor activation. In the case of i.c.v. clonidine, the receptors
      appear to be located postsynaptically and the response is dependent upon intact
      vagal innervation.

PMID- 1362004
TI  - Effects of gadolinium on N-methyl-D-aspartate (NMDA)-induced centrogenic
      arrhythmias.
AB  - In urethane-anesthetized rats, the intracerebroventricular (i.c.v.)
      administration of N-methyl-D-aspartate (NMDA)-induced central arrhythmias. These
      cardiac rhythm disorders could be prevented by the i.c.v. microinjection of
      gadolinium, an inhibitor of exocytosis. These findings suggest that inhibition of
      central neurotransmitter exocytosis could protect against centrogenic
      arrhythmias.

PMID- 1362006
TI  - Resuscitation '92. 1st CPR Congress of the European Resuscitation Council.
      Brighton, England, 20-21 November 1992. Abstracts.

PMID- 1362007
TI  - Cyclosporin A in Rheumatoid Arthritis: Aspects for Long-term Treatment.
      Proceedings of a meeting of the 24th Scandinavian Congress of Rheumatology.
      Malmo, Sweden, 3 June 1992.

PMID- 1362005
TI  - Hepatic function during short-term total parenteral nutrition: effect of exposure
      of parenteral nutrients to light.
AB  - Total parenteral nutrition (TPN) solutions either exposed to light (+L) or
      protected from light (-L) were infused for 5 days through jugular cannulas in
      freely moving rats placed in metabolic cages. At the end of the 5 day period,
      bile flow, biliary inorganic phosphate and biliary gamma-glutamyl transferase
      activity, as well as biliary concentrations of several essential and branch chain
      amino acids were significantly lower in the -L animals compared to +L animals. In
      addition, biliary glutathione was significantly lower in the +L animals. In both
      groups of animals, plasma tyrosine decreased significantly from pre-TPN values
      despite a doubling of plasma phenylalanine concentrations suggesting that
      tyrosine may become a conditionally essential amino acid in rats provided TPN.
      Our findings indicate that short-term parenteral infusion of light exposed TPN
      solutions alters hepatobiliary function as well as amino acid homeostasis and
      that the changes are minimized by light protection of the infusates. The exact
      mechanisms of the contribution of light exposure in the induction of hepatic
      dysfunction remain to elucidated.

PMID- 1362009
TI  - Structural and functional mitochondrial abnormalities associated with high levels
      of partially deleted mitochondrial DNAs in somatic cell hybrids.
AB  - Kearns-Sayre syndrome (KSS) is a progressive and ultimately fatal human
      encephalomyopathy that is associated with large-scale deletions of mitochondrial
      DNA (mtDNA). To gain new insights into the developmental pathobiology of this
      disease, we studied the maintenance and expression of deleted mtDNAs (delta
      mtDNAs) in somatic cell hybrids generated by fusion of HeLacot cells with a KSS
      fibroblast clone containing both wild-type and delta-mtDNAs. We observed that
      delta-mtDNAs were preferentially maintained over the KSS wild-type mtDNAs (wt
      mtDNAs) in almost all isolated hybrid clones. Mitochondrial metabolism was not
      compromised in hybrids containing as much as 70-79% delta-mtDNAs. Two clones
      containing more than 99% delta-mtDNA were severely deficient in oxidative
      phosphorylation and exhibited abnormal, enlarged mitochondria. These clones had
      undetectable levels of mtDNA-encoded polypeptides, but contained normal amounts
      of a nuclear DNA-encoded mitochondrial protein. The data suggest a nonrandom
      pattern of mtDNA segregation in the triplasmic hybrids and a correlation among
      delta-mtDNA, structural mitochondrial abnormalities, and mitochondrial
      dysfunction.

PMID- 1362010
TI  - [Congress 1992. Agreement for good].

PMID- 1362008
TI  - Familial Mediterranean fever and polyarteritis nodosa.

PMID- 1362011
TI  - Further analysis of mutant thiolase protein in fibroblasts from a Japanese boy
      with 3-ketothiolase deficiency.
AB  - We examined the mutant protein of mitochondrial acetoacetyl-CoA thiolase (mutant
      T2) in fibroblasts from a Japanese boy with 3-ketothiolase deficiency. The
      molecular size of the mutant T2 protein, determined by pulse labeling and
      SDS/PAGE, was intermediate between the mature subunit and the precursor of T2. To
      characterize the mutant T2 protein, pulse-labeling and rhodamine 6G inhibition of
      mitochondrial transport in fibroblasts, cell-free translation experiments, and
      family studies by thiolase assay, immunoblotting, and pulse-labeling were carried
      out. The mutant T2 was detectable as early as a 10-min pulse. The probable
      precursor of the mutant T2 was not detectable in either the rhodamine 6G
      inhibition or cell-free translation experiments. In the parents, the K+ ion
      dependency of acetoacetyl-CoA thiolase activity was low and the T2 bands in
      immunoblots were faint. It would thus appear that the parents are heterozygotes
      of this disease. In pulse-labeling, only a band for the mutant T2 was detected in
      the patient and a single band for the normal mature subunit of T2 in the father;
      both bands were detected in the mother. These findings suggested that the mutant
      T2 in the patient was inherited from the mother, and that the expression of
      another mutant allele of the father may be either abolished or scanty.

PMID- 1362012
TI  - The effect of ethylene glycol monomethyl ether and diethylene glycol monomethyl
      ether on hepatic gamma-glutamyl transpeptidase.
AB  - In this paper, we determined whether ethylene glycol monomethyl ether (EGME) and
      diethylene glycol monomethyl ether (diEGME) induce hepatic gamma-glutamyl
      transpeptidase activity. Male adult Wistar rats weighing 220 g were used as
      experimental animals. EGME (100, 300 mg/kg per day) and diEGME (500, 1000, 2000
      mg/kg per day) were administered by gavage for 1, 2 or 5 days or 4 weeks. In the
      4-week study, experimental animals were administered EGME or diEGME once a day
      orally, 5 days/week. EGME treatment increased the serum gamma-glutamyl
      transpeptidase (GGT) level significantly, however, diEGME did not. The activities
      of three other enzymes (SGOT, SGPT and ALP) in serum were not altered by EGME or
      diEGME treatment and thus there was no biochemical indices of hepatic damage by
      EGME or diEGME. EGME treatment increased the GGT activities in the liver and
      lungs. Of the organs examined, the induction of GGT was the greatest in the
      liver. The inducibility in the liver was 216% for the 5-day treatment and 460%
      for the 4-week treatment. A dose-dependent increase of hepatic microsomal GGT
      activity by EGME was observed. On the other hand, renal GGT activities were
      declined to 72% and 60% of control by the 5-day and 4-week EGME treatments,
      respectively. DiEGME did not affect the GGT activities in any of the tissues
      except those of the brain. In the histochemical study, most hepatocytes at the
      periportal zones were stained with GGT staining after the 4-week treatment.
      However, the hepatocytes at the central zones were negative.

PMID- 1362013
TI  - The level of anti-sporozoite antibodies in a highly endemic malaria area and its
      relationship with exposure to mosquitoes. Kilombero Malaria Project.
AB  - The relationship between the humoral immune response to the conserved repeated
      epitope of the Plasmodium falciparum sporozoite and exposure to the mosquito
      vectors was examined in a study carried out in rural southern Tanzania, an area
      highly endemic for malaria. Considerable aggregation of the immune response
      between houses was observed. A statistically significant portion of this
      aggregation could be explained by differences in individual exposure to
      mosquitoes. However, two-thirds of the variance due to aggregation between
      households could not be accounted for, so that antibody level after controlling
      for exposure remained aggregated. Most of the variability in the development of
      the immune response was between individuals within households, and may be related
      to individual differences in behaviour and attractiveness to mosquitoes. The
      observed correlation of the immune response with exposure was due to continual
      exposure during several months, whereas recent exposure had almost no effect on
      the immune response observed in an endemic area. We concluded that in a highly
      endemic area the anti-sporozoite antibody level cannot be used as an indicator of
      recent infection and has only limited use as an indicator of continual infection.

PMID- 1362014
TI  - Radial mass density functions of vitrified helical specimens determined by
      scanning transmission electron microscopy: their potential use as substitutes for
      equatorial data.
AB  - Using STEM dark field images, we have determined linear mass densities and radial
      density profiles of vitrified helical particles. The samples studied are: TMV,
      RNA-free helical polymers of TMV coat protein (TMV-P), Salmonella typhimurium
      bacterial flagellar filaments and Escherichia coli pili. The difference between
      the profiles obtained for TMV and TMV-P shows a maximum at a radius of about 4
      nm, corresponding to the RNA in TMV. Of the peaks that are resolved in X-ray
      diffraction analysis we can resolve the ones for TMV at radii of approximately
      4.2 and approximately 6.7 nm and a shoulder at approximately 7.8 nm. Density
      peaks in bacterial flagellar filaments appear at radii of approximately 4.2,
      approximately 6.5, approximately 8.5, and approximately 10.5 nm. Accurate mass
      data can be obtained if the filaments are embedded in ice layers of uniform
      thickness; their diameters need to be similar to that of the mass standard (TMV)
      when these data are measured in a comparative manner. Ice layers are often not
      uniform, and thickness variations are well revealed in STEM dark field. The
      signal-to-noise ratio and contrast for the transverse projections are lower than
      those measured for freeze-dried specimens: half an order and one order of
      magnitude, respectively. The thinnest uniformly thick ice layer still containing
      a single layer of particles is approximately 10-15 nm thicker than the particles.
      Radial mass density functions that are directly determined in STEM may have a
      potential use as substitutes for the unreliable equatorial data in helical
      reconstructions of TEM bright field images of vitrified specimens.

PMID- 1362015
TI  - Immunodetection of a disease specific PrP fraction in scrapie-affected sheep and
      BSE-affected cattle.

PMID- 1362016
TI  - Extracellular matrix formation by epithelial cells from human polycystic kidney
      cysts in culture.
AB  - Cells from the cysts of patients with autosomal dominant polycystic kidney
      disease (PKD) were grown in vitro under standard conditions without the aid of
      collagen-pretreated surfaces, and both the synthesis and composition of the
      extracellular matrix were investigated. At confluence, PKD cells presented the
      typical features of epithelial cells, but showed a different collagen composition
      from fibroblasts. Compared with normal tubular epithelia (NTE), PKD monolayers
      produced an excess of extracellular matrix, which accounted for 30% of the total
      incorporation of [3H] proline, although this value was considerably lower (by a
      factor of 10) in the case of NTE. Immunohistochemical and electrophoretic
      techniques revealed a complex collagen composition in the extracellular matrix
      which included [alpha (III)]3 and collagen IV. However, part of the collagen
      components remained unidentified in spite of the fact that they exhibited a
      typical M(r) of alpha 1(I) and alpha 2(I) in the presence of urea.
      Immunoprecipitation with monospecific antibodies and Northern blotting with
      specific probes failed to recognize alpha 1(I) and alpha 2(I), but demonstrated
      their presence in fibroblasts. Purification and cyanogen bromide digestion
      demonstrated a strong interhomology in fingerprint peptide composition among the
      uncharacterized collagens synthesized by PKD cells, thus suggesting a common
      identity. These observations document a markedly augmented production of
      extracellular matrix by PKD cultured cells in vitro, and show the presence of
      collagens which do not share homologies with the major collagen molecules. A
      better characterization of extracellular matrix composition is central to any
      comprehension of the cytogenetic mechanisms in vivo.

PMID- 1362017
TI  - Changes in DNA strand breaks in non-parenchymal cells following hepatocyte
      regeneration in CCl4-induced rat liver injury.
AB  - DNA strand breaks (nicks) in non-parenchymal cells (NPCs) in CCl4-induced acute
      or chronic liver injury in rats were detected using an in situ nick translation
      method; their dynamic changes were analysed in relation to the proliferation
      pattern of hepatocytes and NPCs, as revealed by bromodeoxyuridine (BrdU)-uptake.
      In acute injury, hepatocyte proliferation started before centrilobular necrosis
      had occurred, whereas BrdU-labeled sinusoidal NPCs markedly increased only after
      centrilobular necrosis was apparent. DNA breakages in NPCs paralleled the
      proliferation pattern of these cells, suggesting that nicks are physiological,
      and reflect proliferation and activated gene expression. In chronic injury, liver
      cirrhosis developed after 9 weeks, but BrdU-labeling of hepatocytes was almost
      the same level as that in untreated liver. The number of BrdU-labeled NPCs showed
      only a slight increase, while those with DNA breakages were much more frequent in
      the cirrhotic stage, suggesting a significant role for NPCs in the fibrotic
      process. These results indicate that DNA strand breaks in NPCs act as a marker
      for activation states such as proliferation, differentiation and/or activated
      gene expression.

PMID- 1362018
TI  - Distribution of xanthine oxidoreductase activity in human tissues--a
      histochemical and biochemical study.
AB  - Localization of the activity of both the dehydrogenase and oxidase forms of
      xanthine oxidoreductase were studied in biopsy and postmortem specimens of
      various human tissues with a recently developed histochemical method using
      unfixed cryostat sections, poly-(vinyl alcohol) as tissue stabilizator, 1
      methoxyphenazine methosulphate as intermediate electron acceptor and Tetranitro
      BT as final electron acceptor. High enzyme activity was found only in the liver
      and jejunum, whereas all the other organs studied showed no activity. In the
      liver, enzyme activity was found in sinusoidal cells and both in periportal and
      pericentral hepatocytes. In the jejunum, enterocytes and goblet cells, as well as
      the lamina propria beneath the basement membrane showed activity. The oxidase
      activity and total dehydrogenase and oxidase activity of xanthine oxidoreductase,
      as determined biochemically, were found in the liver and jejunum, but not in the
      kidney and spleen. This confirmed the histochemical results for these organs.
      Autolytic rat livers several hours after death were studied to exclude artefacts
      due to postmortem changes in the human material. These showed loss of activity
      both histochemically and biochemically. However, the percentage activity of
      xanthine oxidase did not change significantly in these livers compared with
      controls. The findings are discussed with respect to the possible function of the
      enzyme. Furthermore, the low conversion rate of xanthine dehydrogenase into
      xanthine oxidase during autolysis is discussed in relation to ischemia
      reperfusion injury.

PMID- 1362019
TI  - Cytopathology of PC12 cells infected with Japanese encephalitis virus.
AB  - Infection of a clonal rat pheochromocytoma cell line, PC12, with Japanese
      encephalitis (JE) virus produced successively higher titers of virus in the
      culture fluid during the 72-h experimental period. In electron microscopical
      observation, JE virus entered PC12 cells by direct penetration through the plasma
      membrane at 2 min postinoculation (p.i.) and caused marked cellular hypertrophy
      and extensive proliferation of the cellular secretory system including rough
      endoplasmic reticulum (RER) and Golgi complexes starting 24 h p.i. The
      proliferating RER of the virally infected cells contained progeny virions and
      characteristic endoplasmic reticulum vesicles in its cisternae, and the
      proliferating Golgi complexes contained virions in their saccules. These findings
      indicated that the proliferation of the cellular secretory system occurred in
      association with viral replication and maturation in the system. Seventy-two
      hours p.i., the cellular secretory system of infected PC12 cells showed
      degenerative changes with vesiculation, disorganization, and dispersion of the
      Golgi complexes and fragmentation, focal cystic dilation, and dissolution of the
      RER in the same manner as those seen in the secretory system of JE-virus-infected
      neurons in the mouse brain. Thus, JE-virus-infected PC12 cells seem to be a
      suitable neurogenic cell line for the study of the pathogenic mechanism of JE
      virus. At the same time, the virally infected cells seem to offer an interesting
      cell model for the study of the morphogenesis of the cellular secretory system.

PMID- 1362020
TI  - HTLV-II-specific antisera raised in rabbits immunized with a synthetic peptide of
      HTLV-II envelope protein.
AB  - In order to discriminate HTLV-II from HTLV-I, HTLV-II-specific polyclonal
      antibodies against a synthetic peptide of HTLV-II envelope sequence were raised
      in rabbits. We immunized two adult rabbits with a KLH-conjugated synthetic
      peptide corresponding to the amino acid sequence 171-196 of the HTLV-II envelope
      sequence, which is a specific region for HTLV-II as evaluated with an ELISA
      method. The resulting rabbit antisera to the synthetic peptide reacted with gp46
      of HTLV-II lysates in Western blot analysis but not with that of HTLV-I. Flow
      cytometric analysis and immunohistochemical study revealed that these affinity
      purified antisera recognized some HTLV-II-producing cell lines examined, but not
      HTLV-I-producing cell lines or other cell lines uninfected by HTLV. These
      findings indicate that these antisera specifically recognized the envelope
      glycoprotein (gp46) of HTLV-II and suggest the specificity of this region in the
      immune response to HTLV-II. Such antisera are useful in distinguishing between
      HTLV-I and HTLV-II infection and in determining the presence of individual HTLV
      II-infected cells both in vivo and in vitro, including non-lymphoid cells. They
      may also assist in the elucidation of the pathogenesis of HTLV-II.

PMID- 1362021
TI  - Proliferation of myocardial peroxisomes in experimental rat diabetes: a
      biochemical and immunocytochemical study.
AB  - Myocardial peroxisomes were investigated in normal and diabetic rats. Catalase
      and acyl-CoA oxidase activities were increased in the diabetic rat heart and
      immunoblot analysis showed that both enzyme proteins were markedly enhanced in
      diabetic heart homogenates. After immunoenzyme staining, catalase and acyl-CoA
      oxidase were localized in fine granules in the myocardium, which were increased
      in number in diabetic rats. The numerical density of the granules stained for
      catalase was increased 1.7 times and that for acyl-CoA oxidase 1.8 times,
      compared with controls. Protein A-gold labeling for catalase and acyl-CoA oxidase
      was present in myocardial peroxisomes. The labeling density for both enzymes was
      increased in diabetic rats by 1.6 times for catalase and 1.5 times for acyl-CoA
      oxidase, compared with controls. The results indicate that myocardial peroxisomes
      are increased in the diabetic rat and that this proliferation is accompanied by
      an increase in catalase and acyl-CoA oxidase activities.

PMID- 1362022
TI  - Distribution patterns of proinsulin and insulin in human insulinomas: an
      immunohistochemical analysis in 76 tumors.
AB  - The distribution of proinsulin and insulin immunoreactivity was studied in 76
      human insulinomas and in normal pancreas. One trabecular and two solid
      insulinomas showed the staining pattern of normal beta cells. A "near normal"
      staining pattern (perinuclear proinsulin and diffuse or polarized insulin
      staining) existed in 10 of 27 trabecular and 11 of 44 solid insulinomas. An
      "intermediate" staining pattern (intense perinuclear as well as weaker diffuse
      proinsulin staining with diffuse or polarized insulin staining) was observed in
      10 of 27 trabecular and 20 of 44 solid insulinomas. Different "abnormal" staining
      patterns were found in 6 of 27 trabecular and 6 of 44 solid insulinomas. Of the 5
      glandular insulinomas, 4 exhibited a "near normal" and one an "abnormal" staining
      pattern. No correlation was found between any particular staining pattern and the
      multihormonality or malignancy of the insulinomas. The diffuse labeling for
      proinsulin in about 50% of the insulinomas is suggestive of abnormal prohormone
      processing.

PMID- 1362023
TI  - Three-dimensional study of epithelioid cells by a quick-freezing and deep-etching
      method in muramyl dipeptide-induced granulomas.
AB  - The three-dimensional ultrastructure of epithelioid cells was studied by the
      quick-freezing and deep-etching (QF-DE), as well as the freeze-substitution (QF
      FS) methods. The granulomas were induced in rats by injecting muramyl dipeptide
      (MDP) into the hind footpads. At 3 weeks after the injection, the footpads were
      perfused with a fixative, excised, and quickly frozen to prepare the replica
      membranes. Some unfixed footpads were also quickly frozen and freeze-substituted.
      Dense networks of intermediate filaments, connected with the nuclei, mitochondria
      and other vesicular cell organelles, were observed throughout the cytoplasm of
      epithelioid cells by the QF-DE method. A few actin filaments were located in
      filopodia and just beneath the cell membranes. Interdigitation of the cell
      membranes between adjacent cells was clearly demonstrated by the QF-FS method and
      clathrin-coated pits were identified at the base of interdigitating filopodia. In
      addition, the exact moment of fusion between endosomes and lysosomes was
      ascertained by the same method. These results suggest that the cytoskeletal
      organization of epithelioid cells resembles that of epithelial cells rather than
      actively motile macrophages.

PMID- 1362025
TI  - [Lipid peroxidation and erythrocyte membrane function in congenital heart defects
      in relation to the use of beta-adrenoblockers].
AB  - Oxygen tension in the blood and tissues, lipid peroxidation (LP) intensity
      (content of malonic blood dialdehyde and activity of superoxide dismutase in
      erythrocytes), spectrum of fatty acids and phospholipid composition of
      erythrocytic membranes, their passive K(+) permeability, total ATP content in
      erythrocytes, some other metabolic indices were investigated in 24 patients with
      blue type congenital heart disease. It was shown that these patients showed a
      reduced oxygen tension in the blood and tissues, LP intensification, changes of
      the lipid phase of erythrocytic membranes, disorders of their permeability,
      decrease of intraerythrocytic ATP reserves. Beta-adrenoblocking agents (obsidan,
      anaprilin were used in 10 patients. Reported are clinico-metabolic findings
      indicating a favourable effects of these drugs on LP processes, lipid spectrum of
      erythrocytic membranes, their permeability and bioenergy reactions.

PMID- 1362024
TI  - Comparative sequence analysis and expression of bovine PrP gene in mouse L-929
      cells.
AB  - A cDNA clone encoding bovine scrapie-associated fibril protein, PrP, from a
      bovine brain cDNA library and six amplified genomic DNA clones of bovine PrP were
      characterized. These clones possessed specific characteristics observed in other
      animal PrP genes. However, the bovine PrP was divided into two types by the
      number of repeats. One possessed four octapeptide repetitive sequences, like
      other animal PrP genes, and consisted of 256 amino acids; the other had five such
      repetitive sequences and 264 amino acids. The amino acid sequence of the former
      bovine PrP agreed with that of sheep PrP up to the 165th amino acid from the N
      terminus. Bovine PrP cDNA introduced into mouse L-929 cells were stably
      expressed. The expression level of recombinant bovine PrP in the cells judged by
      immunofluorescence was higher than that of authentic mouse PrP. The recombinant
      PrP comigrated with authentic bovine PrP in SDS-polyacrylamide gel
      electrophoresis, suggesting that the recombinant product was fully glycosylated
      in L-929 cells. Distinct bundles of the intermediate filaments were frequently
      seen at the perinuclear region of the cells.

PMID- 1362026
TI  - [Enzyme activity in the blood serum as a criterion of the severity of acute
      cholecystopancreatitis].
AB  - The activity of lactate dehydrogenase, gamma-glutamyltranspeptidase, alkaline
      phosphatase, 1-antitrypsin was studied in 30 patients with acute
      cholecystopancreatitis of different severity grades. It was found that changes of
      activity of these enzymes depending on the severity of the disease may be
      considered as a criterion of regression of the inflammatory changes in the
      biliary-pancreatic zone as well as a criterion of recovery.

PMID- 1362027
TI  - [The pharmacological correction of reflex stenocardia due to chronic noncalculous
      cholecystitis].
AB  - Results are reported of a study of the effect of benzohexonium electrophoresis on
      the epigastric area in cardiac syndrome due to chronic noncalculous cholecystitis
      in 72 patients. This treatment produced a favourable effect in reflex stenocardia
      as confirmed by data of clinical and paraclinical findings. The authors
      recommended to include benzohexonium electrophoresis in patients with the biliary
      cardiac syndrome in the complex treatment of patients with chronic cholecystitis.

PMID- 1362028
TI  - [Myocardial calcinosis in a juvenile patient with Wermer syndrome (multiple
      endocrine neoplasia type I)].
AB  - We describe the rare case of a 19 year-old patient with multiple endocrine
      neoplasia (Wermer syndrome), presenting with insulinomas as well as primary
      hyperparathyroidism. Echocardiography revealed evidence of calcific deposits in
      the interventricular septum. The latter may be explained by long-standing
      hypercalcemia.

PMID- 1362030
TI  - Proceedings of the International Symposium on Active Immunization against
      Hepatitis A. Vienna, 27-29 January 1992.

PMID- 1362029
TI  - [The status of H2-blocker therapy today].
AB  - In the light of recent findings the therapeutic importance of various H2-blockers
      (e.g. cimetidine, ranitidine, famotidine) in short-term and long-term treatment
      of peptic ulcers is discussed. Special interest is paid to the clinical
      pharmacology (pharmacokinetics, pharmacodynamics) and undesired effects of the
      compounds. New aspects in the pathogenesis of peptic ulcer disease were
      considered, with regard to the pharmacologic profile of H2-blocker.

PMID- 1362031
TI  - Reactogenicity and immunogenicity of inactivated hepatitis A vaccines.
AB  - Two inactivated hepatitis A virus (HAV) candidate vaccine strain were tested,
      derived from strains CLF and HM175. Neither vaccine increased liver enzymes
      levels and reactogenicity was similar to that observed with other alum-absorbed
      products. Antibody responses were dose-dependent and protection against HAV can
      be presumed to last for at least three years. All persons receiving 720 ELISA
      units (El.U) of the CLF vaccine seroconverted after one dose. For the HM175
      vaccine, anti-HAV persisted until month 12 after injections at months 0 and 1,
      suggesting that the third dose of vaccine could be given at any time from month 6
      to 12. A double dose of HM175 vaccine (1440 El.U) given as a single bolus
      resulted in 100% seroconversion by day 14 with a geometric mean anti-HAV level of
      121 mIU/ml. This implies that rapid protection can be induced using large doses
      of inactivated HAV vaccine should time constraints dictate such an approach.

PMID- 1362032
TI  - International Symposium on Atopic Dermatitis. Bergen, Norway, 26-29 May 1991.

PMID- 1362033
TI  - Polyarteritis nodosa with atrophy of the left hepatic lobe.
AB  - A 73-year-old Japanese man with a history of partial gastrectomy due to gastric
      cancer 4 years previously was admitted because of intermittent fever. The patient
      developed abdominal pain, erythema, and myalgia in addition to the fever during
      the final clinical course, and died of acute heart failure. Autopsy disclosed
      atrophy of the left lobe of the liver and acute myocardial infarction. Neither
      metastasis nor recurrence of the cancer was observed. Small- and medium-sized
      arteries of the visceral organs showed various stages of necrotizing vasculitis
      with narrowing of the lumina. The vasculitis was most prominent in the left lobe
      of the liver and in the heart. Narrowing of the portal vein due to portal tract
      inflammation in addition to vasculitis of the hepatic arteries may have induced
      ischemia and infarction, which had resulted in atrophy of the left hepatic lobe.

PMID- 1362034
TI  - Expression of c-fos protein in serotonergic neurons of rat brainstem following
      electro-acupuncture.
AB  - The c-fos proto-oncogene encodes a nuclear phosphoprotein, Fos which has been
      proposed to be a "third messenger" coupling short term extracellular signals to
      long term alteration in cell function. Using double labeling immunocytochemistry,
      the present work demonstrated the co-localization of Fos protein and serotonin in
      the nucleus raphe dorsalis, nucleus raphe centralis superior and rostral
      ventromedial medulla. The results pose an interesting problem, the possible
      relation of Fos protein to the biosynthesis of serotonin, awaiting further
      investigation.

PMID- 1362035
TI  - Acupuncture for low back pain in huang di nei jing su wen. (Yellow Emperor's
      Classic of Internal Medicine Book of Common Questions).
AB  - In Huang Di Nei Jing Su Wen, among the materials which heretofore have no English
      translation, there are three Chapters on pain. One of them was devoted entirely
      to the low back pain. This is certainly an indication of its importance even more
      than 2,300 years ago. Since it still plagues us nowadays, we have translated that
      Chapter of this medical classic to see what we can learn from the ancients. We
      attempted to second guess the ancients in the diagnosis of the various sets of
      symptoms, in the light of western medicine. We discussed the difficulties in
      interpreting the archaic text. We pointed out that there were associations of the
      Mais (i.e., the Meridians) with various sets of symptoms but the loci of puncture
      were rather vaguely described and had no names. We inserted our selections of
      currently used acupoints to match the described loci. We would like to solicit
      our readers' comments.

PMID- 1362036
TI  - Real-time evaluation of anaerobic threshold with rms-EMG of working and
      nonworking muscles during incremental bicycle ergometer test.
AB  - Surface rms-EMG measurement as a real time monitoring method for detecting the
      anaerobic threshold during a bicycle ergometer test was evaluated and compared
      with blood lactate and ventilatory parameters. The study group consisted of 12
      healthy ice hockey players. The anaerobic threshold indicated as dislinearity of
      increase in blood lactate level, ventilatory parameters and myoelectrical
      activity was observed at the work level of 300 (range 270-330) W in each case.
      The linearity disappeared at same time in the rms-EMG-load ratio both in working
      (quadriceps and gastrocnemius) and nonworking (frontalis) muscles. The rms-EMG
      follow-up was easier to perform than measurements of blood lactate and
      ventilatory parameters.

PMID- 1362037
TI  - An introduction to sequential electric acupuncture (SEA) in the treatment of
      stress related physical and mental disorders.
AB  - A method of sequential electrical stimulation to certain acupuncture loci was
      found to be effective in the treatment of stress related physical and mental
      disorders. Recent research found that cerebral serotonin has anti-depressant and
      analgesic effects. It was reported that cerebral serotonin can be released by the
      stimulation of certain acupuncture loci. Omura reported that the stimulation of
      ST36 and GB20 increased intracephalic blood flow. Increasing intracephalic blood
      flow may indirectly increase the quantity of serotonin released. The release of
      serotonin can be enhanced further by sequential stimulation of these acupuncture
      loci. A marked degree of mental relaxation by SEA was shown in this study of 85
      clinical cases of chronic physical disorders, e.g. intractable pain, headache,
      with most disorders complicated by reactive depression. Some of the cases were
      psycho-somatic disorders. The percentage of improvement from slight to remarkable
      between mental disorders (78.8%) and physical disorders (77.1%) is about equal.
      The method of treatment and schematic of the SEA device are discussed and shown.

PMID- 1362038
TI  - Effects of the electrical stimulation of myofascial trigger points with tension
      headache.
AB  - The effects of electrical stimulation by simple pocket size stimulator were
      evaluated on myofascial trigger points by pain threshold (PTH) algometry. The
      study consisted 14 patients with 76 treated trigger points in randomly selected
      double blind cross-over study protocol. The effects of 30 seconds stimulation
      increased the PTH values 0.58 kg/cm2 in study group, but only 0.13kg/cm2 in
      controls (p < 0.01). These results suggested that the stimulation had positive
      effects on myofascial trigger points, but these effects were seen only on the
      treated points.

PMID- 1362039
TI  - Hyperglycemic athymic nude mice: factors affecting in vitro insulin secretion.
AB  - The strain of athymic nude male mice (ANM) developed at the University of
      Southern California (USC) exhibits spontaneous hyperglycemia and relative
      hypoinsulinemia in vivo. To investigate factors that influence insulin secretion
      in this animal model of non-insulin-dependent diabetes mellitus, we utilized the
      isolated perfused mouse pancreas of the ANM-USC and control BALB/c mice. We
      compared in vitro glucose-induced insulin secretion in ANM-USC and control mice,
      inhibition of secretion by somatostatin, and variability of insulin secretion
      over the two-year period it took to complete these experiments. Glucose-induced
      insulin secretion from the isolated pancreas was biphasic in both ANM-USC and
      controls. Insulin secretion was quantitatively equal to or greater than control
      mice, depending on the phase of secretion analyzed and the source of the control
      mice. In contrast to pancreases of control mice, insulin secretion from ANM-USC
      pancreases was relatively resistant to inhibition of insulin secretion by
      somatostatin. Variability in insulin secretion over the two years in which these
      experiments were performed was greater from pancreases of control than that
      observed from pancreases of the ANM-USC. The hyperglycemic ANM-USC mouse does not
      demonstrate diminished insulin secretion in vitro yet is relatively
      hypoinsulinemic in vivo. Thus circulating factors other than somatostatin might
      contribute to the insulinopenic stage in this animal model.

PMID- 1362040
TI  - Exercise interrupts ongoing glucocorticoid-induced muscle atrophy and glutamine
      synthetase induction.
AB  - This study was undertaken to determine whether regular endurance exercise is a
      deterrent to a developing state of muscle atrophy from glucocorticoids and to
      evaluate whether the contractile activity antagonizes the hormonal actions on
      glutamine synthetase, alanine aminotransferase, and cytosolic aspartate
      aminotransferase (cAspAT). Adult female rats were administered cortisol acetate
      (CA, 100 mg/kg body wt) or an equal volume of the vehicle solution for up to 15
      days. Exercise (treadmill running at 31 m/min, 10% grade, 90 min/day) was
      introduced after 4 days of CA treatment, at which time plantaris and quadriceps
      muscle mass had been reduced to 90% of control levels. Running for 11 consecutive
      days prevented 40 mg of the 90-mg loss and 227 mg of the 808-mg loss that were
      subsequently observed in plantaris and quadriceps muscles, respectively, in the
      sedentary animals. Glutamine synthetase mRNA and enzyme activity were elevated
      threefold by glucocorticoid treatment in the deep quadriceps (fast-twitch red)
      muscles after 4 days. Initiating exercise completely interfered with the further
      hormonal induction (to approximately 5-fold) of this enzyme and, after 11
      consecutive days of the exercise regimen, glutamine synthetase mRNA and enzyme
      activity were 58 and 68% of values from CA-treated sedentary animals. In vehicle
      treated groups, basal levels of glutamine synthetase expression were also
      diminished by exercise to approximately 40% of the values in sedentary controls.
      Hormone treatment did not alter either aminotransferase enzyme activity but
      reduced cAspAT mRNA in fast-twitch red muscles by 50%. Exercise abolished the
      glucocorticoid effect on cAspAT mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362041
TI  - Human colon cancer cells express ICAM-1 in vivo and support LFA-1-dependent
      lymphocyte adhesion in vitro.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is a cell surface adhesion
      glycoprotein that mediates leukocyte adhesion through interaction with the
      leukocyte CD11/CD18 adhesion complex. The aim of this study was to determine
      whether ICAM-1 is expressed by normal or neoplastic colonic epithelial cells.
      Immunohistochemical studies on human colonic tissue demonstrated focal ICAM-1
      expression by colonic carcinomas but not by normal colonic epithelium. ICAM-1
      expression by colonic carcinomas showed a positive correlation with the presence
      of a peritumoral inflammatory infiltrate. Surface expression of ICAM-1 was also
      observed in HT-29 cultured human colon cancer cells by both immunohistochemistry
      and enzyme immunoassay. Interferon-gamma and interleukin-1 beta significantly
      increased ICAM-1 surface expression by HT-29 cells in a dose-dependent manner.
      Upregulation of ICAM-1 surface expression became evident some hours after
      cytokine stimulation and was inhibited by both actinomycin D and cycloheximide,
      indicating a requirement for de novo RNA and protein synthesis. HT-29 monolayers
      supported adhesion of human lymphocytes as determined by a quantitative 111In
      labeled leukocyte adhesion assay. Adhesion was mediated in part via interaction
      of ICAM-1 on HT-29 cells with lymphocyte function-associated antigen-1
      (CD11a/CD18) on lymphocytes, as defined by using blocking monoclonal antibodies.
      Expression of ICAM-1 and/or other leukocyte adhesion receptors by neoplastic
      epithelial cells may play a role in directing leukocyte trafficking and leukocyte
      epithelial cell interactions in colonic carcinoma.

PMID- 1362042
TI  - Somatostatin restraint of gastrin secretion in pigs revealed by monoclonal
      antibody immunoneutralization.
AB  - We studied the functional coupling between antral somatostatin and gastrin cells
      in isolated perfused porcine antrum using immunoneutralization with monoclonal
      antibodies against somatostatin. Their binding affinity was 10(11) l/mol, and the
      final binding capacity was 11.7 nmol/ml. Antibody infusion within 1 min increased
      gastrin secretion, reaching a rate of 349 +/- 64% (means +/- SE, n = 7) of basal
      secretion (59 +/- 5 pmol/l) after 5 min. The effect of somatostatin at 10(-9)
      mol/l, which inhibited gastrin secretion from 58 +/- 11 to 14 +/- 3 pmol/min (n =
      4), was abolished by antibody infusion. Electrical stimulation of the vagus
      nerves (n = 7) performed during antibody infusion increased gastrin secretion
      from 224 +/- 61 to 328 +/- 55 pmol/min, not significantly different from the
      increase in control experiments from 43 +/- 9 to 118 +/- 20 pmol/min, indicating
      that the vagal stimulation of gastrin secretion does not depend on mechanisms
      involving somatostatin. We conclude that paracrine antral somatostatin secretion
      is one of the most important factors regulating basal gastrin secretion in pigs.

PMID- 1362043
TI  - Myogenic mechanism for peristalsis in opossum smooth muscle esophagus.
AB  - We studied the propagation of phasic contractions initiated by tetraethylammonium
      (TEA, 1-10 mM), high K+ concentration (10-30 mM), and bethanechol (10(-6) to 10(
      2) M) in a whole organ in vitro preparation of the opossum smooth muscle
      esophagus. TEA initiated phasic contractions that began at all sites along the
      smooth muscle esophagus and propagated in both directions with a velocity similar
      to that of primary peristalsis. Blockade of neural transmission by tetrodotoxin
      (TTX, 10(-7) M) did not prevent contraction propagation. Although a majority of
      contractions initiated by TEA did not propagate the full length of the esophageal
      specimen, with the addition of TTX most contractions initiated by TEA did
      propagate the full specimen length in either direction. High K+ concentration and
      bethanechol elicited propagated contractions similar to those initiated by TEA.
      We conclude that 1) a myogenic mechanism exists for propagation of contractions
      along the smooth muscle esophagus and 2) intramural inhibitory nerves modulate
      the extent of myogenic propagation in the ascending as well as descending
      direction. We suggest that esophageal peristalsis may occur by myogenic
      propagation of contractions that are normally initiated in the proximal smooth
      muscle esophagus by excitatory nerves. Intramural inhibitory nerves may inhibit
      retrograde propagation as well as mediate descending inhibition in advance of the
      peristaltic wave.

PMID- 1362044
TI  - [Effects of intravenous anesthetics on neurons of the central nervous system:
      mechanisms of cellular and molecular action].
AB  - The mechanisms of action of intravenous anaesthetics are not yet completely
      elucidated. Until recently, most of the studies had focused on the interactions
      between anaesthetics and lipid bilayers. It has been proposed that loss of
      consciousness is produced by disorganization of the lipid phase of nerve
      membranes, which impairs the action potential propagation. However, new data
      obtained with sophisticated neuropharmacological tools such as the patch clamp
      technique have recently contributed to challenge this hypothesis. Indeed, several
      lines of evidence suggest that intravenous anaesthetics are thought to induce
      loss of consciousness by blocking the excitatory synaptic transmission. This can
      be achieved presynaptically, by inhibiting glutamate release from nerve endings
      via alterations in the gating properties of voltage-dependent calcium channels.
      Blockade of excitatory synaptic transmission can also occur at the postsynaptic
      level by antagonizing the glutamate receptors of the N-methyl D-aspartate
      subtype. Some anaesthetic agents including ketamine also block the nicotinic
      receptors, however the relevance of this finding with respect to clinical
      anaesthesia requires further investigation. Preliminary data also suggest that
      propofol and etomidate elicit uncoupling of gap junctions between astrocytes,
      which represent a major nonneuronal cell population in the central nervous
      system. This phenomenon might indirectly contribute to the hypnotic action of
      these compounds. Whether loss of consciousness involves preferential target
      structures within the brain remains to be delineated. A better understanding of
      the mechanisms of action of general anaesthetics might contribute to generate new
      agents with more pharmacological selectivity and less undesirable side-effects.

PMID- 1362046
TI  - Typology of Human Relations and Change. Rome, Italy, 17-18 May 1991.

PMID- 1362045
TI  - Effect of age on activation of porcine intestinal guanylate cyclase and binding
      of Escherichia coli heat-stable enterotoxin (STa) to porcine intestinal cells and
      brush border membranes.
AB  - Development of age-dependent resistance to enterotoxigenic Escherichia coli was
      studied, using isolated enterocytes and brush border membranes (BBM) from 7-day
      old and 7-week-old pigs. Binding of 125I-labeled heat-stable (125I-STa)
      enterotoxin to enterocytes and BBM was specific, temperature- and time-dependent,
      saturable, and partially reversible. Scatchard analysis revealed a single class
      of receptors. Mean +/- SD avidity of binding (apparent affinity constant, Ka) of
      125I-STa to enterocytes from 7-day-old and 7-week-old pigs was 2.14 +/- 0.29 x
      10(8) and 2.72 +/- 0.25 x 10(8) L/mol, respectively. Numbers of STa receptors
      were calculated to be 64,903 +/- 2,900/enterocyte for 7-day-old pigs and 53,029
      +/- 3,117/enterocyte for 7-week-old pigs. Numbers of STa receptors expressed per
      milligram of BBM protein from 7-day-old pigs were 2.66 x 10(11), compared with
      2.29 x 10(11) for BBM from 7-week-old pigs. By 5 minutes after addition of STa to
      reaction mixtures, intracellular cyclic guanosine monophosphate concentration
      increased 13.9-fold in enterocytes from 7-day-old pigs and 8.7-fold in
      enterocytes from 7-week-old pigs. The particulate guanylate cyclase activity
      associated with BBM from 7-week-old pigs was slightly more sensitive to low
      amounts of STa, compared with BBM from 7-day-old pigs; however, differences were
      not observed at intermediate and high amounts. These data indicate that lack of a
      secretory response to STa by older pigs is not attributable either to decreased
      numbers of STa receptors or to decreased signal response between the STa receptor
      and membrane-bound guanylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362047
TI  - 11th International Enzyme Engineering Conference. Hawaii, September 22-27, 1991.

PMID- 1362049
TI  - Aggressive behavior and the brain: a different perspective for the mental health
      nurse.
AB  - Mental health nurses often provide care to individuals who have the potential for
      aggressive behavior. The expression of such behavior is influenced by the
      functioning of the central nervous system (CNS). The authors present a framework
      to assist the reader to understand the interrelationships among the limbic
      system, and frontal and temporal lobes as they relate to the expression of
      aggressive behavior. The implications for mental health nursing practice include
      detecting contributing factors such as head injury, temporal lobe epilepsy,
      alcoholism, and dietary imbalances, and interpreting patient behaviors to
      colleagues. Suggestions for proactive interventions are also included.

PMID- 1362048
TI  - The influence of chaperonins on protein folding. A mechanism for increasing the
      yield of the native form.

PMID- 1362050
TI  - Symptom monitoring in schizophrenia: potential for enhancing self-care.
AB  - In this study a symptom self-regulation model was used as a framework to examine
      the characteristics and stability of indicators of illness identified by
      individuals with schizophrenia. Subjects were interviewed to determine if they
      could identify indicators of illness and describe characteristics of their
      primary indicator. Primary indicators of illness from 51 subjects were
      categorized as anxiety-based, depressive, or psychotic. Subjects who identified
      psychotic indicators were more confident that their indicator occurred when they
      were getting ill than subjects with anxiety-based or depressive indicators, and
      subjects who identified psychotic and depressive indicators reported that their
      indicators were more troublesome than those identifying anxiety-based indicators.
      Anxiety-based indicators were reported by subjects to occur more frequently than
      indicators from the other two categories. Findings from a follow-up interview of
      28 subjects 1 year later showed that approximately half reported either the same
      primary indicator of illness or identified an indicator in the same category
      (anxiety-based, depressive, or psychotic) as they had 1 year previously. The
      implications of the findings for enhancing self-care through monitoring symptoms
      are discussed.

PMID- 1362051
TI  - Antipsychotic drug doses in a schizophrenia inpatient unit.
AB  - Dose-effect studies have found that 600 mg/day of chlorpromazine (or its
      equivalent) is generally sufficient to treat acute psychosis. This paper reports
      on the doses of antipsychotic medication prescribed for inpatients in a
      Schizophrenia Unit at an Australian state hospital. Fifty five percent of
      patients received daily doses equivalent to more than 600 mg of chlorpromazine
      and 26% received daily doses equivalent to more than 1500 mg of chlorpromazine.
      Low potency drugs were prescribed in lower doses than high potency drugs.
      Patients prescribed depot medication tended to receive higher doses of medication
      than those prescribed oral medication only.

PMID- 1362052
TI  - Treatment of childhood anxiety disorders using behaviour therapy and
      pharmacotherapy.
AB  - Although the treatment of childhood anxiety disorders can be approached from
      numerous theoretical perspectives, the concentration of research has been on the
      efficacy of behaviour therapy. Behaviour therapy procedures are briefly described
      and evaluated, including systematic desensitisation, flooding, modelling,
      reinforcement and cognitive procedures. We also review research findings on
      pharmacotherapy, focusing on benzodiazepine and antidepressant usage. Finally,
      several conclusions are drawn concerning the scientific and clinical status of
      these treatment approaches for childhood anxiety disorders.

PMID- 1362055
TI  - [Address to the annual general assembly of the Hellenic National Nurses'
      Association by the President St. Papamicroule, 12-2-1992].

PMID- 1362053
TI  - Psychotic symptoms preceding ocular deviation in a patient with tardive
      oculogyric crises.
AB  - This report describes a patient with schizophrenia who developed episodes of
      ocular dystonia as a delayed side effect of neuroleptic medication. Each episode
      was preceded and accompanied by marked agitation, stereotypic behaviour and
      exacerbation of hallucinations. Both the psychotic and dystonic symptoms
      responded to anticholinergic medication. The theoretical and practical
      implications of this observation are discussed.

PMID- 1362054
TI  - Co-variation between biological markers and self-reported alcohol consumption. A
      two-year study of the relationship between changes in consumption and changes in
      the biological markers gamma-glutamyl transpeptidase (GGT) and average volume per
      erythrocyte (MCV) among problem drinkers.
AB  - Co-variations between self-reported alcohol consumption and the biological
      markers MCV (average volume per erythrocyte) and GGT (gamma-glutamyl
      transpeptidase) over a 2-year period were studied in a group of 84 men and 53
      women recruited to out-patient treatment by advertisements in the press. Upon
      admission, the drinking pattern of the participants during the preceding year was
      registered in detail. The participants were also medically examined, and blood
      samples taken. All the participants were followed up by new personal interviews,
      medical examinations and new blood sampling after 3, 9, 25 and 21 months. For the
      group as a whole, alcohol consumption was significantly lower at the end of the
      observation period than at admission. GGT was also decreased, but not MCV. Both
      self-reported consumption and the values for the biological markers showed large
      inter-individual and intra-individual variations during the observation period.
      The biological markers seemed to co-vary to a limited degree with changes in
      reported consumption. Both GGT and MCV seemed to have a low sensitivity but a
      high specificity to changes in consumption. Both markers also seemed to be
      somewhat more useful in identifying decreases than increases in consumption. The
      markers GGT and MCV should be used with caution in connection with therapeutic
      counselling to individuals.

PMID- 1362056
TI  - [19th Annual National Nursing Congress, Rhodos, 19-21 May 1992].

PMID- 1362057
TI  - Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2
      receptors, clozapine occupies D4.
AB  - Dopamine (DA) D2, D3, and D4 receptors are targets for antipsychotic drugs. The
      recent cloning, deoxyribonucleic acid sequencing, and brain location of these
      receptors provide new insight on the DA hypothesis of schizophrenia, particularly
      for the basis of antipsychotic therapy of schizophrenia. In schizophrenia brain
      tissue, D2 receptors are elevated and have lost the link to D1 receptors. Brain
      positron-emission tomography studies of patients may also reveal elevated D2,
      depending on the method used. Hallucinations and positive symptoms are blocked
      when about 70% of the D2 receptors are occupied by neuroleptic drugs. An analysis
      of the literature indicates that therapeutic concentrations of antipsychotic
      drugs (in the patient's cerebrospinal fluid or plasma water) act primarily at D2
      receptors, with the exception of clozapine, which acts at D4 receptors.

PMID- 1362059
TI  - History in the Bay of Naples.

PMID- 1362058
TI  - Processed MHC class I alloantigen as the stimulus for CD4+ T-cell dependent
      antibody-mediated graft rejection.
AB  - The traditional view of graft rejection is one of direct recognition of
      allogeneic MHC molecules by effector T cells, the phenotype of which may be
      predicted by the nature of the MHC disparity. In this article, Andrew Bradley and
      colleagues discuss recent evidence that suggests this view may be an
      oversimplification, and argue that additional effector mechanisms, such as
      alloantibody, need to be reconsidered.

PMID- 1362061
TI  - [The Dutch contribution].

PMID- 1362060
TI  - An association between a Bc1I restriction fragment length polymorphism of the
      glucocorticoid receptor locus and hyperinsulinaemia in obese women.
AB  - Obesity is likely to be a multifactorial disease with an important genetic
      component. Animal models of genetic and experimentally induced obesity suggest
      that glucocorticoid receptor (GR) activity plays a role in the aetiology and
      maintenance of the obese state. Glucocorticoid activity appears to be essential
      for the development of hyperinsulinaemia and subsequent fat deposition. In
      humans, glucocorticoid excess is associated with central fat distribution. We
      have therefore investigated the restriction fragment length polymorphisms of the
      human GR gene locus (GRL) and have sought associations of specific alleles with
      anthropometric measurements and indices of insulin secretion and resistance in
      obesity. Fifty-six extremely obese, unrelated, nondiabetic premenopausal British
      Caucasian females and 43 age-matched, normal weight controls were studied. The
      obese subjects were characterized by fat distribution (waist to hip ratio),
      insulin secretion and insulin resistance (fasting insulin (FI)), an index of
      insulin resistance (HOMA), stimulated insulin secretion during an oral glucose
      tolerance test and insulin-mediated glucose disposal, steady-state plasma
      glucose). A Bc1I polymorphism (fragments of 4.5 and 2.3 kb) demonstrated
      significant association with indices of glucose metabolism in obesity; those
      subjects homozygous for the 4.5 kb fragment had elevated FI (Pc = 0.012) and HOMA
      (Pc = 0.012) values. The genotypic and allelic frequencies of the GRL Bc1I
      polymorphism were otherwise similar in obese and normal weight subjects. We
      postulate that the GRL Bc1I polymorphism may directly affect GR gene expression,
      or be in linkage disequilibrium with a possible mutation within one of three
      exons of the GR gene, and thereby modulate GR transcriptional activity on target
      genes involved in glucose and insulin homeostasis.

PMID- 1362063
TI  - Distribution of somatostatin-immunoreactivity in the brain of the larval lamprey
      (Petromyzon marinus).
AB  - The detailed distribution of somatostatinergic neurons and fibre tracts in the
      brain of larval lamprey was studied in serially sectioned material using
      immunocytochemical techniques. Neurons were found to be arranged in four nuclei:
      a hypothalamic nucleus consisting of both small cerebrospinal fluid-contacting
      neurons and larger non-contacting neurons, a thalamomesencephalic nucleus and two
      isthmotrigeminal reticular nuclei. The hypothalamic nucleus is the first to
      differentiate. Analysis of young larvae showed that somatostatin-immunoreactivity
      first appeared in hypothalamic cells (12 mm larvae), while it appeared later in
      the other nuclei. The different somatostatin-immunoreactive fibre tracts
      innervate different regions of the brain. In addition, somatostatin
      immunoreactive fibres originating from hypothalamic neurons were found in the
      anterior neurohypophysis, which suggests the presence of a hypothalamohypophysial
      somatostatinergic system in lampreys.

PMID- 1362062
TI  - Development of tyrosine hydroxylase-, dopamine- and dopamine beta-hydroxylase
      immunoreactive neurons in a teleost, the three-spined stickleback.
AB  - The development of catecholaminergic neuronal systems in the brain of a teleost,
      the three-spined stickleback, was studied through embryonic to early larval
      stages by immunocytochemistry using specific antibodies against dopamine,
      tyrosine hydroxylase and dopamine beta-hydroxylase. By analysing the
      spatiotemporal patterns of development for the catecholaminergic nuclei, possible
      homologies with nuclei in amniote brains have been identified. The noradrenergic
      neurons in the isthmus region of the rostral rhombencephalon originate in the
      same manner as the A4-A7 + subcoeruleus group in mammals. Their developmental
      characteristics show the largest similarities with the subcoeruleus group of
      birds and mammals, although some features are shared with developing A6 (locus
      coeruleus) neurons. Catecholaminergic neurons never appear during development in
      the ventral mesencephalon of the three-spined stickleback. A group of large
      dopaminergic neurons that accompany the cerebrospinal fluid (CSF)-contacting
      neurons follows the border between the hypothalamus and the ventral thalamus into
      the caudal hypothalamus, where they are continuous with the dopaminergic neurons
      in the posterior tuberculum. They are thus topologically comparable with the
      dopaminergic neurons of the zona incerta in mammals. The dopaminergic CSF
      contacting neurons that line the median, lateral and posterior recesses of the
      third ventricle do not contain tyrosine hydroxylase-immunoreactivity at any
      developmental stage. This indicates that they take up and accumulate exogenous
      dopamine or L-dihydroxyphenylalanine, and do not synthesize dopamine from
      tyrosine at any developmental stage. Tyrosine hydroxylase-immunoreactive neurons
      appear in the pineal organ on the day of hatching (120 h post-fertilization).
      They were still observed in 240-h-old larvae, but are absent in the pineal organ
      of adult sticklebacks. The initial appearance and subsequent differentiation of
      catecholaminergic neurons in the stickleback embryo follow essentially the same
      spatial and temporal pattern as in amphibian, avian and mammalian embryos. This
      observation supports the hypothesis that morphologically, topologically and
      chemically similar monoaminergic neurons in different vertebrate classes are
      homologous.

PMID- 1362064
TI  - The role of cytokines in tumor immunotherapy. Report on the 2nd Frankfurt
      International Cytokine Symposium 25-27 June 1992, Frankfurter Hof, Frankfurt,
      Germany.
AB  - The conference, organized by Profs. Mitrou, Bergmann (Frankfurt), Huber (Mainz)
      and Niederle (Leverkusen), concentrated almost exclusively on the role of
      cytokines in cancer. The majority of presentations concerned IFN-alpha, IL 2 or
      TNF-alpha, but G-CSF, GM-CSF, IL 4, IL 10 and TGF-beta were not neglected.
      Presentations achieved a laudable balance between basic science and clinically
      oriented studies. The present report emphasizes the clinical aspects; proceedings
      of the entire meeting will be published by S. Karger AG, Basel.

PMID- 1362065
TI  - Axonal Transport and the Cytoskeleton. Satellite symposium of the 13th biennial
      meeting of the International Society for Neurochemistry. Cairns, Queensland,
      Australia, July 20-22, 1991.

PMID- 1362067
TI  - Rapid, reliable ligation-independent cloning of PCR products using modified
      plasmid vectors.

PMID- 1362066
TI  - Effect of methylation inhibitors on gene expression in HL-60 cells.
AB  - The methylation inhibitors Neplanocin A (Nep A), 3'-deazaadenosine (dzAdo), and 3
      deaza(+/-)aristeromycin (Dari) were tested for their effect on the expression of
      histone H2B, actin, and the protooncogenes c-myc, and v-fos. Nep A and Dari bind
      to the S-adenosylhomocysteine hydrolase resulting in the accumulation of S
      adenosylhomocysteine, while dzAdo served as a substrate for the enzyme. With
      dzAdo, inordinant amounts of 3-deazaadenosylhomocysteine (dzAdoHcy) accumulated
      in the cell, provided L-homocysteine (Hcy) was present. When added at sublethal
      concentrations, the methylation inhibitors had little or no effect on c-myc, v
      fos, histone H2B, or actin expression, nor did any significant number of the drug
      treated cells demonstrate myeloid characteristics. However, growth and gene
      expression were markedly inhibited upon the addition of Hcy and dzAdo. One of the
      earliest effects of dzAdoHcy on HL-60 cells was the disappearance of c-myc mRNA.
      Within 1 h of the addition of dzAdo and Hcy, only trace amounts of c-myc mRNA
      were detectable. After 4-5 h v-fos, histone H2B, and actin mRNAs also decreased
      to about 40% of control levels. Differences in the stability of preexisting mRNAs
      would appear to account for these results. Within 1 h following the addition of
      dzAdo and Hcy, the synthesis of rRNA and mRNA were completely blocked as measured
      by the incorporation of [3H]uridine.

PMID- 1362068
TI  - Preparation of plasmid DNA by sequential enzymatic digestion.
AB  - A new method for the preparation of plasmid DNA from Escherichia coli, sequential
      enzymatic digestion, is described. The method is based on sequential and
      selective enzymatic digestion of all components of E. coli except for the
      supercoiled plasmid DNA. The key enzymes are exonuclease I and exonuclease III
      that specifically hydrolyze linear chromosomal DNA and are unable to attack
      supercoiled plasmid DNA under controlled conditions. Isolated plasmid DNA can be
      sequenced and digested with restriction enzymes.

PMID- 1362069
TI  - Evaluation of DNA probe removal from nylon membrane.
AB  - Genetic fingerprinting is one of the most challenging applications of any
      hybridization membranes. Forensic DNA fingerprinting typically uses samples in
      the range of 100-400 ng of genomic DNA. To ensure the ability to successfully
      reprobe the samples, it is imperative that repeated stripping of sample DNA be
      minimized while stripping of the probe DNA be maximized. By using standard
      dilutions of K562 cell line, we compared the following three stripping
      techniques: NaOH at 25 degrees C, formamide (HCONH2) at 65 degrees C and 0.1 x
      standard saline citrate and 0.1% sodium dodecyl sulfate at 95 degrees C (high
      temperature stripping). The largest amount of genomic DNA was stripped from the
      membrane with NaOH, with the other two techniques removing less. Formamide and
      high-temperature procedures resulted in a loss of approximately 5-10 ng of DNA
      per strip. In contrast, the NaOH resulted in a loss of approximately 10-20 ng per
      strip.

PMID- 1362070
TI  - [XLIV Annual Reunion of the Spanish Society of Neurology. Barcelona, 7-12
      December 1992. Abstracts].

PMID- 1362071
TI  - [Pulmonary artery involvement in Takayasu arteritis. A case of right ventricular
      failure as presentation form].
AB  - Pulmonary involvement in Takayasu's artery disease has been reported since 1940
      with an incidence of 14 to 56%. However, the development of severe pulmonary
      hypertension is an extremely rare event in the natural course of the disease. The
      authors report a case of a 62 year old male presenting with severe congestive
      heart failure of recent onset. The initial evaluation and routine exams suggested
      the presence of pulmonary hypertension of unknown etiology. The absence of left
      radial pulse in the physical examination led to the performance of a complete
      angiographic study which confirmed the diagnosis of Takayasu's arteritis with
      pulmonary involvement and severe pulmonary hypertension.

PMID- 1362072
TI  - The activity of dipeptidyl peptidase II and dipeptidyl peptidase IV in mice
      immunized with type II collagen.
AB  - We investigated the activity of peptidases in the serum of mice with experimental
      polyarthritis that was induced by the injection of type II collagen, an
      experimental model of human rheumatoid arthritis. The activity of dipeptidyl
      peptidase II (DPP II) was increased and that of dipeptidyl peptidase IV (DPP IV)
      was decreased resulting in the significant increase of the serum DPP II/DPP IV
      ratio in the polyarthritic mice compared with that of controls. These results
      indicate that the DPP II/DPP IV ratio is a novel index of disease activity in
      mice with collagen-induced polyarthritis and may be useful in assessing the
      activity of rheumatoid arthritis in humans.

PMID- 1362073
TI  - Choice of enzymes for mapping based on CpG islands in the human genome.
AB  - The frequencies of sites for rare-cutting restriction enzymes in 2.9 million bp
      of human genomic DNA sequence in the EMBL database have been determined and
      compared with the expected frequencies. Rare cutters can be divided into four
      groups based on certain features of their recognition sites. Mlu, I, Nru I, Spl
      I, and Pvu I are predicted to cleave genomic DNA most infrequently, which is
      borne out by the fragment lengths observed for Mlu I and Nru I. Thus, these four
      enzymes are ideal for making long-range maps based on pulsed-field
      electrophoresis. Other enzymes like Not I are useful for making more detailed
      maps. Finer maps for identification of CpG islands and associated genes should
      involve several rare cutters including Eag I, Sac II and Bss HII. A cluster of
      sites for at least two such enzymes is a good indicator of a CpG island, and 78%
      of the island-associated genes can be located in this way.

PMID- 1362074
TI  - Hox codes and positional specification in vertebrate embryonic axes.
AB  - We have compared the ways in which vertebrate Hox genes are used in the
      patterning of three distinct embryonic contexts, the branchial region, the
      somites, and the limb. We have identified common features of the three systems,
      but have suggested on the basis of their differences (in both embryological
      properties and use of Hox genes) that it is better to consider each as an
      independent system for regional specification. Nevertheless, there are sufficient
      common features to expect that exploitation of the distinct experimental
      advantages of each system will provide important insights to the mode of
      operation of the others.

PMID- 1362075
TI  - Effects of cyclosporin A on resident and passenger immune cells of normal human
      skin and UV-induced erythema reactions.
AB  - Cyclosporin A (CyA) has proved effective in various dermatological diseases, but
      its mechanisms of action within the skin are still ill-defined. In order to
      characterize more clearly the cellular targets of CyA we examined its effects on
      skin immune cells in normal and UVB- and PUVA-irradiated skin by means of a three
      step immunoperoxidase reaction and immunofluorescence double-labelling technique.
      The CyA-induced depletion of epidermal Langerhans cells equals that seen with UVB
      or PUVA alone. CyA alone has no effect on the number and distribution of dermal
      cells. CyA modulates the UV irradiation-induced changes by: (i) inhibiting the
      UVB- and PUVA-induced ICAM-1 expression by keratinocytes and (ii) suppressing the
      PUVA-induced upregulation of CD11a expression by macrophages (72 +/- 12% of Ki
      M8+ macrophages express CD11a with PUVA, compared with 20 +/- 5% with CyA + PUVA,
      P < 0.001). Neither treatment affected ICAM-1 expression by endothelial cells. In
      addition, CyA increases PUVA minimal phototoxicity dose from 10 +/- 2.6 J/cm2
      (PUVA alone) to 15.3 +/- 3.1 J/cm2 (CyA + PUVA), (P < 0.001). In conclusion, the
      effects of CyA on the skin include a down-modulation of the PUVA-erythema
      reaction, associated with a direct or indirect modulation of adhesion molecule
      expression.

PMID- 1362076
TI  - Biochemical and haematological markers of alcohol intake in Ghanaians.
AB  - The serum gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST),
      urate and triglyceride and mean cell volume (MCV) were determined in 60 total
      abstainers, 56 social drinkers and 100 alcoholics. Both enzymes and urate showed
      progressive rise with increasing alcohol intake. The mean cell volume was only
      moderately elevated. Gamma-glutamyltransferase (GGT), aspartate aminotransferase
      (AST), and urate are sensitive enough to detect people who take in alcohol
      regularly and yet may be regarded as normal and not alcohol dependent.

PMID- 1362078
TI  - Major histocompatibility complex located complement C4 and steroid 21-hydroxylase
      gene rearrangements in couples with recurrent spontaneous abortions.
AB  - Major Histocompatibility Complex (MHC) class III located complement C4 and
      steroid 21-hydroxylase (21OH) genes, which form various deletion and duplication
      units, were studied by TaqI Restriction Fragment Length Polymorphism (RFLP) in 58
      Finnish couples who suffered recurrent spontaneous abortions (RSA). The gene
      rearrangements found in the RSA couples did not differ from those in the
      controls.

PMID- 1362077
TI  - The preferential expansion of functional CD4+ lymphocyte populations in vitro.
AB  - We describe a simple and inexpensive chemical procedure for the selective
      expansion of human CD4+ lymphocytes. The method employs L-leucine methyl ester
      (LME) to deplete monocytes and large granular lymphocytes, as well as to inhibit
      growth of CD8+ lymphocytes. LME treatment eliminates granular cells, but most
      CD8+ lymphocytes, B-lymphocytes, and CD4+ lymphocytes remain. Peripheral blood
      mononuclear cells (PBMCs) from normal and HIV-positive individuals are treated
      with LME for 1 h at ambient temperature and cultured in the presence of IL-2 to
      expand the cell number. Stimulation with the T-cell mitogens concanavalin A,
      phytohemagglutinin, or OKT3 antibody augments lymphocyte expansion and within 1-3
      weeks the culture is greatly enriched (90-100%) in CD4+ lymphocytes. LME-treated
      lymphocytes expand up to 10-fold during culture in the presence of IL-2 alone and
      up to 400-fold following treatment with T-cell mitogens. The immune function of
      LME-treated and expanded peripheral blood lymphocytes was examined using the
      response to the recall antigens tetanus toxoid and Candida albicans. Fresh PBMCs
      exposed to these recall antigens proliferated readily. Similarly, LME-treated
      lymphocytes following expansion responded to these recall antigens with good
      fidelity to the original PBMC response patterns in four of six donors. The
      expanded and LME-treated lymphocytes also exhibited good mitogen responses in
      three of three donors. The LME procedure allows for the simple and inexpensive
      generation of expanded, immunologically functional, CD4+ lymphocytes.

PMID- 1362079
TI  - A new restriction fragment length polymorphism of the human TNF-B gene detected
      by AspHI digest.

PMID- 1362080
TI  - Restriction fragment length polymorphism analysis of zoo animals using HaeIII and
      four single-locus probes.
AB  - Using HaeIII as the restriction endonuclease, restriction fragment length
      polymorphism analysis of dried blood samples from various animals was conducted.
      Single-locus probes D2S44, D10S28, D1S7, and D4S139, as well as monomorphic probe
      D7Z2, were used to examine for banding patterns. If bands were present, the
      samples were further examined for heterogeneity (whether single or multiple bands
      were observed) and polymorphism (whether variation in band location was shown
      between the animals studied within a species). Blood samples from animals,
      including primates, were obtained from Miami Metrozoo, Miami, Florida. Some of
      the animals were non-related individuals while others were related. Banding
      patterns were observed in colobus' for D2S44, D1S7, and D4S139; owl monkeys for
      D2S44; gorillas for D2S44 and D4S139; gibbons for D2S44 and D4S139; siamangs for
      D2S44, talapoins for DiS7; cranes for D1S7; and otters for D1S7. Based upon
      these, all of the animals for which a conclusion could be drawn appeared to be
      homozygous and monomorphic (exhibited only an invariant single band) for the loci
      examined except colobus' for D4S139, gorillas for D4S139, cranes for D1S7, and
      otters for D1S7.

PMID- 1362081
TI  - Effect of operating variables on the separation of DNA molecules by capillary
      polyacrylamide gel electrophoresis.
AB  - The influence of operating conditions on the separation of double stranded DNA
      molecules in capillary polyacrylamide gel electrophoresis is presented in
      continuation of previous work. In this study, an equation was derived that
      relates the effects of electrophoresis variables such as gel concentration, field
      strength, molecular weight and temperature to the migration velocity. As a model
      system, phage phi X174 DNA restriction fragments obtained by digestion with
      HaeIII have been examined. As an illustration of optimized conditions, DNA
      molecules up to the 10(3) base pair range were separated at high temperature (50
      degrees C) in less than 6 min and with efficiencies as high as 5000 plates m-1 s
      1.

PMID- 1362082
TI  - Isolation and characterization of type 1 fimbriae from a chicken pathogenic
      Escherichia coli serotype O78.
AB  - Type 1 fimbriae from chicken pathogenic Escherichia coli strain PDI-386 (serotype
      O78) was purified and characterized. Because of the acid-induced
      autoagglutination (T. Sekizaki, Y. Nakasato, and I. Nonomura, J. Vet. Med. Sci.
      54, 493-499, 1992), the fimbriae could be easily purified by repeating acid
      sedimentation, washing, and dissolving in buffer (pH 8.0). In electron
      microscopy, the purified fimbriae showed a filament of 8 nm in diameter and 10
      microns in average length. The molecular mass of the protein subunit of the
      purified fimbriae estimated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) was 19,000 daltons. The amino acid composition and its
      NH2-terminal sequence were similar to the previously described one of the
      Klebsiella pneumoniae type 1 fimbriae. Moreover, there was an immunological
      relatedness between them. These results indicated that a molecular diversity
      found between the fimbriae of E. coli and that of K. pneumoniae has already been
      existed among chicken pathogenic E. coli strains.

PMID- 1362083
TI  - Increase of methionine aminopeptidase activity in hyperplastic Leydig cells of
      rat cryptorchid testis: a histochemical study.
AB  - Histochemical study on the changes of the aminopeptidase activities in rat testes
      after surgically-induced cryptorchidism was conducted comparing them with the
      histochemical changes in regenerated hepatic cells of the partially
      hepatectomized rat liver. Methionine-aminopeptidase in Leydig cells gradually
      increased after cryptorchid was induced, whereas the enzyme activity in
      regenerated hepatic cells decreased. These histochemical observations were
      coincident with the data obtained by enzyme assay. The present study has
      indicated that in the rat cryptorchid testis the increase of methionine
      aminopeptidase activity was caused by hyperplastic Leydig cells.

PMID- 1362084
TI  - Antagonism of medetomidine sedation by atipamezole in pigs.
AB  - The efficacy of atipamezole as a medetomidine antagonist was evaluated in pigs.
      The atipamezole doses (intramuscularly) were 80, 160, 320 and 480 micrograms/kg
      of body weight, which were one, two, four and six times higher than the preceding
      medetomidine dose (80 micrograms/kg, intramuscularly). Atipamezole effectively
      reversed medetomidine-induced sedation, and the optimal action was seen at doses
      of 160 and 320 micrograms/kg. Recovery from sedation was quick and smooth, and
      adverse effects such as hyperactivity or tachycardia were minimal with either
      dose.

PMID- 1362086
TI  - Assessment of myocardial perfusion, metabolism and pharmacology using positron
      emission tomography.
AB  - Positron emission tomography is a non-invasive radionuclide imaging technique
      which enables in vivo assessment of regional cardiac function. When used with
      appropriate radiotracers and kinetic models, it can provide quantitative
      measurements of myocardial perfusion, metabolism and pharmacology. The
      development of quantitative measurements should help to decrease much of the
      ambiguity in the interpretation of data that often occurs. The short half-life of
      the radionuclides used allows the imaging of more than one function to be
      performed conveniently within the same scanning session with a low radiation dose
      to the subject. This integrated approach provides a means for investigating in
      vivo the physiology and pathophysiology of the human heart.

PMID- 1362085
TI  - Initial studies of embryonic transplants of human hippocampus and cerebral cortex
      derived from schizophrenic women.
AB  - Human fetal brain tissue was obtained from first-trimester elective abortions of
      two women who also had schizophrenia. Portions of the embryonic hippocampus or
      cerebral cortex were transplanted into the anterior eye chamber of
      immunologically compromised athymic nude rats. In this environment, embryonic
      brain tissue derived from normal women generally continues organotypic growth and
      development for many months. Although initial survival after transplantation was
      normal, the tissue derived from schizophrenic women manifested less robust
      growth. However, cells in the transplants showed typical neuronal
      differentiation, with development of different neuronal types, such as pyramidal
      cells, granule cells, and gamma-aminobutyric acid (GABA)-containing interneurons.
      Rhythmic electrical activity was also observed, indicative of some local synaptic
      organization. The presence of messenger RNA (mRNA) for brain-derived
      neuronotrophic factor (BDNF) was observed using in situ hybridization. The reason
      for the decreased rate of growth of these transplants remains unknown and the
      significance of the finding cannot be assessed from only two fetuses. However,
      these preliminary findings suggest that fetal transplants may be a useful model
      system for the detection of developmental pathogenic processes in the expression
      and transmission of schizophrenia.

PMID- 1362087
TI  - Simultaneous transcription of eleven cytokines in human alloreactive T lymphocyte
      clones after stimulation by phorbol ester and A23187.
AB  - Human alloreactive T lymphocyte clones derived from cells invading a rejected
      kidney allograft, were analyzed for their ability to transcribe eleven cytokine
      genes under phorbol ester (PMA) plus calcium ionophore (CaI A 23187) stimulation.
      In addition to the positive signal previously obtained for IL-2 transcripts,
      strong specific patterns were seen with cytoplasmic dot hybridizations for IFN
      gamma and GM-CSF mRNAs in all the 17 clones screened. For the remaining
      transcripts (IL-3, IL-4, IL-5, IL-6, TNF alpha, LT, M-CSF and HILDA/LIF), these
      techniques proved to be inadequate. Northern-blots were therefore performed on
      three clones exhibiting different phenotypes (CD4+ CD8- non cytotoxic, CD4+ CD8-
      cytotoxic and CD4- CD8+ cytotoxic). Positive specific signal with the eleven
      probes could be obtained. Nevertheless, the IL-6 message was found only in the
      helper clone and the TNF alpha transcript appeared at a later time point compared
      to the other cytokine messages (its maximum expression was observed around 24
      hours post-stimulation). In conclusion, we demonstrate that under PMA+CaI
      activation, one clone is able to simultaneously transcribe at least eleven
      lymphokine genes. Except, perhaps for IL-6, the pattern of lymphokine
      transcription did not permit us to distinguish between different lymphocyte
      subsets.

PMID- 1362088
TI  - Identification of the B cell derived T cell colony promoting activity to soluble
      CD23.
AB  - We previously reported that supernatants of phytohemagglutinin (PHA)-stimulated
      normal human B cells (NBCsup) contain a T cell colony promoting activity. NBCsup
      were able to (a) increase the number of secondary colonies generated under PHA
      and interleukin-2 (IL-2) stimulation by peripheral blood-derived primary T colony
      cells, (b) enhance the ability of CD4+ but not CD8+ peripheral blood T cells to
      form agar colonies in the presence of PHA and IL-2 and (c) support in vitro
      differentiation of CD2-3-4-8- prothymocytes into CD2+3+4+ T cells. This activity
      was therefore refered to as Prothymocyte Differentiating Activity (PTDA).
      Subsequent studies pointed to striking biochemical and cell source homologies
      between this B cell derived factor and the 25-kDa soluble CD23 (sCD23). sCD23 has
      been recently found to display prothymocyte differentiating activity.

PMID- 1362089
TI  - Angiotensin II-induced proliferation of cultured murine mesangial cells:
      inhibitory role of atrial natriuretic peptide.
AB  - Angiotensin II (ANG II), as a single factor, induces proliferation in a cultured
      murine mesangial cell line (MMC). This study was undertaken to evaluate a
      possible influence of atrial natriuretic peptide (ANP) on this ANG II-induced
      proliferation. ANP (10(-7) M) for 2 min significantly increased intracellular
      cGMP levels in MMC. This increase in cGMP was totally abolished when cells were
      preincubated for 5 min with 10(-7) M ANG II. Stimulation of intracellular cGMP
      formation by sodium nitroprusside was also decreased in the presence of ANG II.
      The ANG II-mediated inhibition of ANP-stimulated intracellular cGMP levels was
      blocked by Dupont 753, suggesting signal transduction through ANG II receptors of
      the AT1 class. ANP (10(-7) M) for 24 h completely abolished the ANG II-induced
      proliferation in MMC. However, 10(-7) M ANP had no significant effect on
      mitogenesis induced by platelet-derived growth factor or epidermal growth factor.
      Furthermore, ANP reduced the ANG II-stimulated expression of the proliferating
      cell nuclear antigen, a cofactor of polymerase delta that is active in the S
      phase of the cell cycle. The addition of 10(-3) M N-monobutyryl-guanosine 3':5'
      cyclic monophosphate or 8-bromo-guanosine 3':5'-cyclic monophosphate also blocked
      the ANG II-induced proliferation. ANP (10(-7)) M for 24 h had no significant
      influence on the expression (number and dissociation constant) of ANG II
      receptors as determined by binding assays. These results suggest that, besides
      the previously shown vasoconstrictive and vasodilating effects, complex
      interactions between ANG II and ANP exist that can modulate mesangial cell
      growth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362090
TI  - Increased circulating intercellular adhesion molecule-1 in adult T cell leukemia
      patients.

PMID- 1362092
TI  - Differentiation of isolates of Discula umbrinella (Teleomorph: Apiognomonia
      errabunda) from beech, chestnut, and oak using randomly amplified polymorphic DNA
      markers.
AB  - Genetic variation in 30 isolates of Discula umbrinella derived from beech,
      chestnut, and oak was assessed using randomly amplified polymorphic DNA (RAPD)
      and restriction fragment length polymorphic markers. Polymerase chain reaction
      amplifications with 17 primers produced 134 different DNA fragments. Three RAPD
      fragments were subsequently used for Southern hybridization. By these techniques
      up to four different individuals could be detected in the same leaf. The presence
      of several individuals within a single leaf indicates a finely tuned balance
      between the endophyte and its host. Cluster analysis of all arbitrary primed
      amplified DNA fragments showed that the isolates could be placed into four groups
      corresponding to their host origin. The high percentage of private RAPD variants
      within groups is consistent with low gene flow.

PMID- 1362091
TI  - [Tropaphen in experimental drug therapy of cor pulmonale].
AB  - The influence of alpha-adrenoblocking drug tropaphen on cardio- and haemodynamics
      under experimental lung-heart failure was studied in dogs. The findings suggest
      effectiveness of tropaphen administration in such pathology shown by a decrease
      of lung hypertension and heart overload, significant increase of the contractile
      activity and relaxation properties of myocardium of both ventricles and in
      cardiac pump function optimization.

PMID- 1362093
TI  - Didanosine therapy in patients intolerant of or failing zidovudine therapy.
AB  - OBJECTIVE: To examine the effect of didanosine (2',3'-dideoxyinosine, ddI) on
      surrogate markers of HIV infection (CD4+ lymphocyte count, p24 antigen) and to
      evaluate the incidence of adverse effects from ddI. DESIGN: This study was
      performed as a retrospective chart review of patients who were enrolled in
      Bristol-Myers Squibb's expanded-access program for ddI. SETTING: Patient records
      were obtained from primary care physicians' offices. PATIENTS: Twenty-five HIV
      infected patients diagnosed with AIDS or AIDS-related complex (ARC) who were
      intolerant of zidovudine (ZDV) therapy or deteriorating clinically despite ZDV
      therapy and were eligible for inclusion in the ddI expanded-access program.
      INTERVENTION: ddI was administered orally in a citrate-phosphate buffer every 12
      hours. Patients were followed by their private physician on a monthly basis. MAIN
      OUTCOME MEASURES: Laboratory analysis at each month included CD4+ lymphocyte
      count, hemoglobin, hematocrit, serum amylase, uric acid, serum triglycerides, and
      p24 antigen. Mean CD4+ cell count, serum amylase, hemoglobin, and uric acid at
      each month during ddI therapy were compared with baseline concentrations for nine
      months. RESULTS: Patients had received prior ZDV therapy for an average of 15.5
      months before starting ddI. Mean CD4+ cell counts increased from 53.9/mm3 at
      baseline to 72.4/mm3 after 4 months of therapy (p = 0.04) but returned to
      concentrations comparable with those at baseline after 5 months. One case of
      documented pancreatitis, two cases of suspected pancreatitis, and nine cases of
      peripheral neuropathy occurred during ddI therapy. The estimated mean cumulative
      dose for the development of neuropathy was 1.16 g/kg, which is lower than
      previously reported. CONCLUSIONS: Patients who have received prolonged therapy
      with ZDV or who have low initial CD4+ counts may not have sustained increases in
      CD4+ counts from ddI therapy. Also, development of peripheral neuropathy may
      occur at lower cumulative doses in these patient populations.

PMID- 1362095
TI  - Nonneuroleptic treatment of disruptive behavior in organic mental syndromes.
AB  - OBJECTIVE: To summarize the literature describing nonneuroleptic treatments of
      unacceptably disruptive behavior in chronically institutionalized psychiatric
      patients with mental retardation, autism, organic brain syndrome, and dementia.
      DATA SOURCES: Relevant articles were identified from a MEDLINE search of the
      above diagnoses linked with "aggression" and "psychomotor agitation." Additional
      references were found in the bibliographies of these articles. STUDY
      SELECTION/DATA EXTRACTION: The studies reviewed were limited to prospective
      evaluations of nonneuroleptic drug therapy of these behavior disturbances. Case
      reports, case series, and retrospective studies were excluded. Studies of
      patients with schizophrenia, affective disorders, and personality disorders were
      also excluded. DATA SYNTHESIS: Studies of lithium, beta-blockers, carbamazepine,
      benzodiazepines, and buspirone were adequate for review. As a rule, these studies
      are hampered by poor design. The lithium studies suggest that mentally retarded
      patients with behavior disturbances may respond to lithium treatment. The beta
      blocker studies suggest improvement in patients with mental retardation, autism,
      organic brain syndrome, and dementia. Neuroleptic discontinuation or a decrease
      in dose was possible in some patients. The carbamazepine studies were
      inconclusive. Carbamazepine should be reserved for patients with concomitant
      seizure disorders. Benzodiazepines were helpful in treating elderly demented
      patients. Thus far, buspirone has been evaluated in only a few, poorly designed
      studies and is not yet recommended for treatment of behavior disturbances.
      CONCLUSIONS: Legislation has restricted the use of neuroleptics in many patients
      receiving long-term healthcare. Despite the questionable validity of the studies
      reviewed, lithium, beta-blockers, carbamazepine, and benzodiazepines may be
      considered as alternatives to neuroleptics in selected cases.

PMID- 1362094
TI  - Adjunctive medications in patients receiving thrombolytic therapy: a multicenter
      prospective assessment. The Virginia Multicenter Thrombolytic Study Group.
AB  - OBJECTIVE: To describe the use of adjunctive therapies in patients with acute
      myocardial infarction receiving thrombolytic agents. DESIGN: Data were collected
      prospectively by the study-site investigator or the emergency department
      physician caring for the patient. Study participation did not influence
      thrombolytic regimen selection or the adjunctive therapies ordered. SETTING:
      Thirteen Virginia hospitals representing a cross-section of hospitals in the
      state. Eleven are urban medical centers; four have graduate medical education
      programs. PARTICIPANTS: Patients were included in the study if the decision to
      administer thrombolytic therapy was made in the emergency department. MAIN
      OUTCOME MEASURES: Concomitant medications administered during the first six hours
      after initiation of thrombolytic therapy. RESULTS: Two hundred ten patients (aged
      57 +/- 14.1 y) were evaluated. Ninety-five percent of these patients were treated
      with tissue plasminogen activator, 3 percent received anisoylated plasminogen
      streptokinase activator complex, and 2 percent received streptokinase. Ninety-one
      percent of the patients also received heparin, the most commonly used adjunctive
      medication; 77 percent concomitantly received lidocaine; 62 percent received
      aspirin; and only 19 percent received a beta-blocker. CONCLUSIONS: Our data
      provide a reference point for future studies to determine factors that influence
      the selection of adjunctive agents for treating patients with acute myocardial
      infarction receiving thrombolytics.

PMID- 1362096
TI  - Evaluation of the reliability and validity of a measure of anxiolytic drug-use
      intensity for pharmacoepidemiologic studies.
AB  - OBJECTIVE: To assess the reliability and validity of a proposed new standard of
      drug-use intensity, the minimum marketed dose (MMD), using anxiolytic drugs as
      models. DESIGN: Retrospective, cohort design. SETTING: Staff model, nonprofit
      health maintenance organization. PATIENTS/PARTICIPANTS: Eighty-five patients who
      obtained one or more prescriptions for an anxiolytic, antidepressant, or sedative
      hypnotic drug during three consecutive one-year time periods. Fifty-nine patients
      had a prescription filled during the year before the study. RESULTS: For
      anxiolytic drugs, the magnitude of the average correlation for the MMD measure of
      drug-use intensity was greater than the total number of prescriptions and the
      total number of dosage units. Discriminant validity was demonstrated because the
      MMD was not correlated with measures in unrelated therapeutic categories. Summed
      MMD units were shown to significantly predict physical impairment (criterion
      validity). CONCLUSIONS: The MMD measure of drug-use intensity was reliable and
      valid for anxiolytic drugs. These findings suggest that information gathered from
      automated prescription records may be a useful indicator of drug-use intensity in
      pharmacoepidemiologic studies.

PMID- 1362097
TI  - Comment: beta-adrenergic agonists for acute, severe asthma.

PMID- 1362098
TI  - Increased frequency of the heterozygous switch region of IgA2 in Japanese
      patients with IgA nephropathy.
AB  - The relation between IgA hyperproduction and restriction fragment length
      polymorphism (RFLP) of the immunoglobulin heavy chain switch (S) region was
      examined in Japanese patients with IgA nephropathy (IgAN) using Southern blot
      hybridization. Polymorphism in the S regions of IgM, IgA1 and IgA2 (SA2) was
      detected. A significant increase in the frequency of heterozygous phenotype of
      SA2 was shown in the patients. These patients showed a significant increase in
      the amount of serum IgA, IgA bearing cells and levels of proteinuria. Although
      two reports on RFLP of the S region have been published in Europe, the results
      differed. A comparison of the three reports showed different frequencies in the
      phenotype of the S region between Caucasian and Japanese patients. These results
      suggested that there is heterogeneity at the S region in IgAN patients in various
      countries and that this polymorphism might be associated with IgA hyperproduction
      and the development of proteinuria in Japanese patients.

PMID- 1362099
TI  - Beta(+)-thalassemia with hemochromatosis.
AB  - A 64-year-old man was admitted due to ascites. Laboratory data showed hemoglobin
      6.7 g/dl, mean corpuscular volume 82 fl, and ferritin 2,360 ng/ml. Liver biopsy
      showed hemochromatosis. The diagnosis of beta-thalassemia was suggested by a
      decreased ratio of beta/alpha-globin synthesis in vitro (0.26). Cloning of the
      beta-globin gene showed A-to-G mutation in the first base of the ATA box. He was
      confirmed to be homozygous for this specific allele by beta-gene complex analysis
      and analysis of Southern blot hybridization of the alpha- and beta-globin genes.
      His two sons were confirmed to be heterozygous for this allele.

PMID- 1362100
TI  - Genetic analysis of systemic lupus erythematosus: association with a T cell
      receptor restriction fragment length polymorphism in Japanese patients.
AB  - Many studies have suggested the involvement of multiple genetic loci in the
      development of systemic lupus erythematosus (SLE). We have analyzed the
      correlation between various genetic markers and the susceptibility to SLE. In
      this study, the association of SLE and restriction fragment length polymorphism
      (RFLP) of T cell receptor gene was evaluated. The cDNA for constant regions of
      alpha, beta and gamma chain were used as probes and RFLPs were analyzed after
      digestion with Eco RI, Bam HI, Pst I, Pvu II, Hind III and Bgl II. Among them,
      polymorphisms were detected using Bgl II- and Hind III-digested DNA and C beta as
      a probe. Association with SLE in Japanese patients was found only after digestion
      with Hind III. The absence of the 13 kb polymorphic band appeared to be
      correlated with the development of SLE (relative risk = 4.78).

PMID- 1362101
TI  - Fine-structure mapping of the complex locus Odc-rs5 relative to Igk and distal
      loci.
AB  - Odc-rs5 was previously identified as a complex locus closely linked to the Igk
      complex on mouse Chromosome (Chr) 6 and comprising at least five copies of a
      sequence related to the mRNA encoding ornithine decarboxylase (ODC) in the
      genomes of mice of some inbred strains and at least seven copies in others
      (Richards-Smith and Elliott, Mammalian Genome 2: 215, 1992). In the present
      study, Odc-rs5 was shown to be composed of at least seven copies of the ODC
      sequence in both the Odc-rs5a and Odc-rs5b haplotypes. Based upon the
      distribution of DNA restriction fragments (RFs) that had previously been
      associated with Odc-rs5a or Odc-rs5b among 42 mice of inbred laboratory strains
      having various haplotypes at Igk and in mice of two congenic strains [B6.PL-Ly
      2a, Ly-3a(75NS)/Cy and B6.PL-Ly-2a,Ly-3a(85NS)/Cy] and a backcross-derived stock
      (NAK) known to be recombinant within Igk, a fine structure map of Odc-rs5 was
      deduced relative to Igk and more distal loci. Odc-rs5-derived RFs were located to
      three distinct regions within and/or distal to Igk and to a fourth site between
      (Ly-3, Ly-2) and Raf-1. Additionally, DNAs from 19 mice of inbred strains and
      random-bred stocks derived from wild progenitors trapped at various locations
      were analyzed and found to exhibit an unexpected variety of combinations of RFs
      associated with the two Odc-rs5 haplotypes most frequently observed among inbred
      laboratory strains of mice.

PMID- 1362103
TI  - Chromosomal localization of the murine stress protein gene encoding glucose
      regulated protein 78 (BiP).

PMID- 1362105
TI  - The effects of salmeterol and salbutamol on ciliary beat frequency of cultured
      human bronchial epithelial cells, in vitro.
AB  - Studies investigating mechanisms of mucociliary clearance have suggested that
      beta 2-adrenergic agents may significantly influence ciliary activity of
      epithelial cells and therefore play a vital role in the maintenance of functional
      integrity of the airways. We have cultured human bronchial epithelial cells, from
      surgical explants and investigated the effects of salbutamol and salmeterol, in a
      time- and dose-dependent manner, on the ciliary beat frequency (CBF) of these
      cells. Prior to and at several times after exposure to either salbutamol (10(-8)
      to 10(-3) M) or salmeterol (10(-8) to 10(-4) M), the epithelial cells were
      monitored for CBF and on the basis of data obtained from these studies, the
      effect of 10(-6) M propranolol was investigated in the presence of optimal
      concentrations of salbutamol and salmeterol. Salbutamol was optimally active at a
      concentration of 10(-4) M and caused a transient but significant increase in the
      CBF from baseline level of 8.6 +/- 0.4 to 9.6 +/- 0.5 Hz (P < 0.05), after 2 h
      incubation. In contrast, salmeterol was maximally active at a concentration of
      10(-6) M and caused a significantly rapid and prolonged increase in CBF from a
      baseline value of 9.2 +/- 0.4 to 10.9 +/- 0.6 Hz (P < 0.02) and 10.6 +/- 0.8 Hz
      (P < 0.05) after 15 min and 24 h incubation, respectively. Propranolol (10(-6) M)
      abrogated the salbutamol- but not the salmeterol-induced increases in
      CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362104
TI  - Theophylline produces over-additive relaxation of canine tracheal smooth muscle
      when combined with beta-agonists: the dose-response relationship.
AB  - The interaction between theophylline (T) and the beta-agonists albuterol (A) and
      isoproterenol (I) was examined using canine cervical tracheal smooth muscle
      devoid of epithelium contracted with 0.1 or 0.3 microM methacholine. Greater
      functional antagonism with beta-agonists vs. T was confirmed and an ability of T
      to potentiate beta-agonist relaxation was demonstrated. The EC50 for T increased
      from 0.13 +/- 0.02 to 0.37 +/- 0.07 mM (mean +/- SEM) in preparations contracted
      with 0.1 or 0.3 microM methacholine, respectively, while that for I increased
      from 0.036 +/- 0.008 to 0.17 +/- 0.03 microM, a significantly larger change (P <
      0.025). In tissues contracted with 0.3 microM methacholine and pretreated with 10
      micrograms/ml of T IC50 values from composite concentration-response curves for I
      and A were displaced to the left and Emax was increased (56.6 to 71.5% for I, 44
      to 61% for A, P < 0.0002). Addition of 10 micrograms/ml T resulted in relaxations
      which exceeded that calculated by the fractional product method for additive,
      independent action (P < 0.0001 for I, P < 0.0002 for A at 0.3 microM
      methacholine), suggesting that at least part of T's action was over-additive.
      Five, 10 and 20 micrograms/ml T enhanced the effectiveness of single
      concentrations of I by factors of 1.47 +/- 0.14 (P < 0.05), 2.72 +/- 0.26 (P <
      0.01) and 5.34 +/- 0.55 (P < 0.01), respectively, in preparations contracted with
      0.1 microM methacholine: I enhanced the effectiveness to a lesser degree. Using
      two approaches, positive interaction or over-additivity between T and beta
      agonists has been demonstrated.

PMID- 1362106
TI  - Migration of peptide-immunoreactive local circuit neurons to rat cingulate
      cortex.
AB  - The times of origin of neurons immunoreactive for somatostatin (SRIF),
      cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were
      determined using a combined immunohistochemical-autoradiographic technique. 3H
      thymidine (3H-dT) was injected into pregnant rats on gestational day 13 (G13),
      G15, G17, G19, or G21. Animals were killed on postnatal day 30, that is, after
      the completion of neuronal migration. Sections of the brain including posterior
      cingulate cortex (area 29), visual cortex (area 17), and somatosensory cortex
      (area 3) were processed serially for peptide immunoreactivity and
      autoradiographically for labeling with 3H-dT. SRIF- and CCK-immunoreactive
      neurons were cogenerated and comigrated according to an inside-to-outside
      sequence. Accordingly, neurons in layer VI were born on G13, neurons in
      intermediate layers were born on G15-G17, and neurons in layer II/III were born
      on G19-G21. In contrast, VIP-positive neurons did not follow such a sequence.
      Neurons in all layers of cortex were generated at relatively constant rates
      between G13 and G21. VIP-immunoreactive neurons were the only known subpopulation
      of neurons that did not migrate into cortex by an inside-to-outside sequence.
      Thus, the migration of local circuit neurons to cingulate cortex follows patterns
      that are similar to those discerned in more differentiated cortical areas.

PMID- 1362107
TI  - Pattern generation.
AB  - The study of rhythmic motor pattern generation continues to be dominated by
      preparations in which cellular and circuit mechanisms can be bridged. Using these
      preparations, basic questions such as how circuits can be modified in order to
      generate a large number of patterns have begun to be answered. The action of
      neuromodulators on second messengers and channel proteins can provide a link
      between molecular studies and behavior. There has been a large increase in the
      use of computer simulations, and their usefulness as a way of studying pattern
      generation is growing.

PMID- 1362108
TI  - Mechanisms of respiratory rhythm generation.
AB  - In mammals, a three-phasic respiratory rhythm is generated by a network of
      various types of neurons in the lower brainstem. The cellular mechanisms of
      rhythmogenesis involve cooperative interactions between synaptic processes and
      specific membrane properties. The network seems to be driven by extrinsic sources
      in mature animals, whereas in the immature network pacemaker neurons might be
      involved.

PMID- 1362109
TI  - Control of functional systems in the brainstem and spinal cord.
AB  - Progress has been made in the identification of cells, circuits, and networks
      involved in certain important subcortical functional systems, including
      swallowing, chewing, posture and locomotion, and in the shared mechanisms for
      selecting the network for specific motor tasks, including a role for excitatory
      amino acids for network activation, the shaping of the network by inhibitory
      control, and the selection of inputs and modulation of outputs by monoamines and
      other agents.

PMID- 1362110
TI  - Toxic effect of bile acid ingestion in rats.
AB  - Ingestion of raw bile from some grass carp fish has been reported to be
      associated with impairment of renal function in some Chinese people. 5 alpha
      cyprinol, the main bile alcohol in these fish, has been suggested as the toxic
      compound causing electrolyte imbalance. In this study, we attempted to determine
      whether oral administration of pure bile acids also affects the electrolyte
      balance in rats. Twenty-four female Long-Evans rats weighing 200-250 g were used.
      Conscious cannulated animals were prepared and studied with gastric intubation of
      15%, 4.8 mL/kg of sodium cholate (SC), sodium deoxycholate (SD), and water; there
      were three groups of eight rats in each. A drastic drop in blood pressure,
      elevation of the ST segment of the EKG, increases in plasma potassium, hydrogen,
      blood urea nitrogen, and oxygen partial pressure were found. All rats treated
      with bile acids died within 24 hours. Six SD rats and three SC rats died within
      eight hours after oral administration of bile acid. It is concluded that the
      effects of feeding rats bile acids are very similar to the toxic action seen
      after ingestion of grass carp bile.

PMID- 1362111
TI  - Generation of neutrophil-chemoattractant by degradation of tumor cell membrane
      protein.
AB  - Polymorphonuclear leukocytes (PMN) infiltrating into tumors are assumed to be the
      result of a migration in response to a tumor-derived chemotactic factor. It is
      hypothesized that tumor-derived chemotactic factors, which are supposed to be in
      aggregates, can be exposed by proteolytic degradation of the tumor cell membrane
      protein (TCM). The TCM suspension made from either Sarcoma 180 or Ehrlich ascites
      tumor after incubation with Varidase at 37 degrees C for six to eight weeks is
      referred to as a degraded TCM protein (DTCM). The purpose of this study was to
      detect whether or not the DTCM was chemotactic for PMNs. Chemotactic activity was
      assayed by a sponge-matrix model and expressed in the number of PMNs infiltrating
      into the sponge per mouse after intrasponge injection of the DTCM, dose range,
      0.4-0.005 mL. Maximal response to DTCM was restricted to the limited dose between
      0.01 and 0.02 mL. Quantities of DTCM > 0.02 mL caused a response in roughly
      reciprocal proportion to the dose of DTCM. Changes in the circulating leukocyte
      count in response to an intravenous (i.v.) injection of DTCM was biphasic. The
      initial relative leukopenia was followed by leukocytosis within 24 hours in rats
      surviving the effect of DTCM doses < 0.5 mL. However, in rats with i.v.
      injections of higher doses, profound leukopenia was present at death. The mice,
      after an intraperitoneal (i.p.) injection of DTCM, dose range, 0.5-1.0 mL, died
      between 16 and 24 hours after the injection. The bone marrow of these mice showed
      complete depletion of PMNs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362112
TI  - Adult bacteremic pneumonia: bacteriology and prognostic factors.
AB  - Bacteremic pneumonia is a highly specified subgroup of pneumonia that is
      potentially life-threatening. In order to find out the prognostic factors in this
      subgroup of pneumonia, we conducted a 40-month retrospective analysis of 70 cases
      in our hospital. The male to female ratio was 54:16. Forty-one cases were
      community-acquired bacteremic pneumonia (CABP), and 29 cases were nosocomial
      bacteremic pneumonia (NBP). Both CABP and NBP were predominated by gram-negative
      bacteria. Klebsiella pneumoniae was the most common microorganism isolated in
      both CABP and NBP. The overall mortality was 62.9% (44/70). There was no
      significant difference in the mortality between CABP (61.0%) and NBP (65.5%).
      After univariate analysis of all possible prognostic factors, 10 variables were
      found to have significantly poor prognostic values. They were: 1) the presence of
      septic shock; 2) the use of ventilatory support; 3) the presence of radiologic
      spread; 4) treatment in an intensive care unit; 5) male gender; 6) the
      development of adult respiratory distress syndrome; 7) Klebsiella bacteremic
      pneumonia in patients with an alcohol habit; 8) patients with ultimately fatal
      underlying diseases; 9) an initial AaDO2 > 200 mmHg; and 10) an initial arterial
      pH < 7.25.

PMID- 1362113
TI  - Serum sialyl stage-specific embryonic antigen levels in adenocarcinoma of the
      lung.
AB  - The serum levels of sialyl stage-specific embryonic antigen (SSEA-1) in 67
      patients with adenocarcinoma of the lung were studied to assess their values for
      diagnosis. A solid-phase immunoradiometric sandwich assay with an FH6 monoclonal
      antibody was used. Another 49 healthy adults, 52 patients with benign pulmonary
      diseases, and 142 lung cancer cases with cell types other than adenocarcinoma
      were evaluated for comparison. The mean (+/- S.D.) levels (U/mL) for
      adenocarcinoma of the lung, lung cancer other than adenocarcinoma, benign
      pulmonary diseases and normal subjects were 182.9 +/- 309.7, 53.5 +/- 22.6, 38.9
      +/- 17.1 and 30.5 +/- 6.5, respectively. The mean serum sialyl SSEA-1 level was
      significantly higher in adenocarcinoma of the lung, compared with lung cancer
      other than adenocarcinoma (p < 0.001), benign pulmonary diseases (p < 0.001), or
      normal subjects (p < 0.001). For late stage (Stages III and IV, n = 58)
      adenocarcinoma of the lung, the mean (+/- S.D.) serum sialyl SSEA-1 level (204.3
      +/- 327.6 U/mL) was significantly higher than that of earlier stage (Stages I and
      II, n = 9) adenocarcinoma of the lung (39.9 +/- 19.3), p < 0.001. There was no
      statistical difference among the mean serum levels of various histologic types of
      lung cancer other than adenocarcinoma (p > 0.05). In the lower range of values,
      considerable overlap existed between adenocarcinoma of the lung and lung cancer
      other than adenocarcinoma. However, very high sialyl SSEA-1 levels (> 140 U/mL)
      were only encountered in late stage adenocarcinoma of the lung (22/58).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1362114
TI  - Prognosis of thymic carcinoma: analysis of 16 cases.
AB  - Primary thymic carcinoma is a rare malignant neoplasm which arises from the
      thymic epithelium. Between May 1982 and September 1990, 16 patients with thymic
      carcinomas, diagnosed at Chang Gung Memorial Hospital, were reviewed. Their ages
      ranged from 19 to 75 years, with a median of 40 years. Males predominated (male
      to female ratio was 11:5). The most common presenting symptoms were chest pain,
      cough, body weight loss and dyspnea. No paraneoplastic syndromes were seen. Chest
      roentgenograms of 15 patients revealed a mediastinal mass, but a definitive
      diagnosis could not be made until surgery. Adjacent mediastinal tissues were
      invaded, or adhered to, by all the tumors. Six distinct histologic types were
      found, squamous cell carcinoma being the most common (seven cases). The primary
      treatment of surgical resection was attempted in 14 patients, but only in five
      cases could the tumors be completely resected; two had a biopsy only.
      Radiotherapy, with or without chemotherapy, given postoperatively, achieved
      additional local control in seven of the nine partially resected patients (77%).
      Distant metastasis occurred in nine of 16 patients (56%). Lymph nodes, bone and
      lung were the most common metastatic sites. Chemotherapy with cisplatin and/or
      adriamycin-based regimens was given to patients who had distant metastasis, but
      the responses were unsatisfactory. The overall survival at one, three and five
      years was 88%, 51% and 31%, respectively. The median survival was 30 months. The
      median survival of patients with pure squamous cell carcinoma (> 49 months) was
      superior to that of patients with other histologic types (18 months; p < 0.01).

PMID- 1362115
TI  - Risk factors for hyperinsulinemia in chlorpropamide-treated diabetic patients: a
      three-year follow-up.
AB  - To elucidate the presence of chronic hyperinsulinemia and its relation to
      clinical and biochemical parameters, 112 (53 females and 59 males) Chinese non
      insulin-dependent diabetes mellitus (NIDDM) patients under chlorpropamide therapy
      were closely monitored for three years. Clinical and biochemical risk factors for
      chronic hyperinsulinemia were studied by regular monitoring of body weight,
      fasting insulin levels and various biochemical data. Chronic hyperinsulinemia was
      defined as a mean fasting level over 20 microU/mL (highest level observed in 35
      non-diabetics). Among 112 diabetics, 52 cases (46.4%) showed chronic
      hyperinsulinemia. From simple linear regression analysis, female gender, high BMI
      and elevated triglyceride and uric acid levels were correlated with insulin
      levels (p < 0.05). The presence of diabetic complications (retinopathy,
      neuropathy and nephropathy) and the degree of glycemic control were not
      significantly different between the normoinsulinemic and hyperinsulinemic groups.
      In conclusion, 1) NIDDM patients treated with chlorpropamide showed higher
      fasting insulin levels with 46.4% of them meeting the criteria for chronic
      hyperinsulinemia; 2) female gender, uric acid, BMI and triglyceride were the risk
      factors correlated with chronic hyperinsulinemia; and 3) the presence of diabetic
      complications and diabetic control correlated poorly with chronic
      hyperinsulinemia.

PMID- 1362116
TI  - Plasma prorenin and renin levels in non-insulin-dependent diabetes mellitus.
AB  - To investigate plasma renin and prorenin levels in non-insulin-dependent diabetes
      mellitus (NIDDM) and their relation with autonomic nervous function and renal
      impairment, we measured plasma renin and prorenin levels in 39 NIDDM patients.
      The patients included 21 males and 18 females, aged 56.3 +/- 6.2. Thirty-four
      normal age-matched subjects served as controls. Autonomic nervous function was
      evaluated in 23 patients by the performance of cardiovascular reflex tests. The
      plasma renin concentration was measured by angiotensin I generation after the
      addition of an exogenous substrate. Plasma prorenin was activated by trypsin. The
      results showed that the plasma renin concentration was similar between NIDDM
      patients and normal subjects, while plasma prorenin was higher in NIDDM patients.
      No correlation existed between the plasma renin or prorenin levels and autonomic
      nervous function. The patients with abnormally high levels of prorenin also had a
      similarly high plasma renin level but not a high creatinine clearance (Ccr) or
      daily proteinuria. The plasma renin level was correlated inversely with daily
      proteinuria but not with Ccr. These results suggest that the high plasma prorenin
      levels in some diabetic patients cannot be explained by renal impairment, poor
      prorenin conversion or autonomic dysfunction. The hyporeninemia in some patients
      may be related to microvascular involvement of the kidney.

PMID- 1362117
TI  - Energy requirements in response to high protein feeding in young male adults.
AB  - Two experiments were conducted to investigate the effects of moderate (MPI) and
      high (HPI) levels of protein intake on energy utilization in 12 healthy young
      male adults who were confined to a metabolic unit for 56 days. The amount of
      energy supplied was adjusted so that the subjects could maintain a relatively
      constant body weight, which was used as the criterion to see whether the body was
      under an energy balance. All foods were supplied in conventional style. In the
      first experiment, six young men were given a diet of 1.18 g (MPI) and 1.74 g
      (HPI) protein/kg of body weight/day in consecutive periods. In the second
      experiment, another six young men were studied at a protein intake of 1.08 g
      (MPI) and 2.00 g (HPI)/kg/day. The results indicate that both energy intake and
      energy expenditure are independent of protein intake. The average gross energy
      intake of the subjects was between 2,300 to 3,240 kcal/day, corresponding to a
      light-to-moderate grade of energy expenditure. The efficiency of energy
      utilization did not differ significantly between the moderate and high levels of
      protein intake in adults.

PMID- 1362118
TI  - Complications of laparoscopic cholecystectomy: an analysis of 200 cases.
AB  - Complications of the initial 200 cases of laparoscopic cholecystectomy (LC) at
      the Cathay General Hospital within a period of 11 months were reviewed from video
      documents of the operations and clinical records. The major complication rate was
      3.5%, including one common bile duct (CBD) injury (0.5%), three retained CBD
      stones (1.5%), one subphrenic fluid accumulation (0.5%), one liver abscess (0.5%)
      and one cystic duct stump bile leakage (0.5%). All major complications were
      cholecystectomy-related, and only one of the seven occurred in cases of acute
      cholecystitis. Age and sex were not related to its occurrence. The rate of minor
      complications ranged from 0.5% to 10%; they were: shoulder and back pain (10%),
      gall bladder perforation (10%), retained stones in the abdominal cavity (5%),
      transient nausea and diarrhea (5%), extension of umbilical port to a mini
      laparotomy (3.5%), prolonged operation time > three hours (2%), subcutaneous
      emphysema (1.5%), wound infection (1.5%) and prolonged ileus (0.5%). The minor
      complications occurred largely in patients with acute cholecystitis. The
      complications occurred mostly during the early period of our study, indicating a
      learning period phenomenon. These could have been avoided if we had had a
      thorough knowledge of the potential complications and had strictly followed the
      principles of laparoscopic surgery. We conclude that LC is safe and the
      complication rate is not higher than that for open cholecystectomy. Most of the
      complications are preventable if LC is performed by qualified biliary surgeons
      following strict precautions.

PMID- 1362119
TI  - Comparison of omeprazole and nizatidine in the treatment of duodenal ulcers.
AB  - This study compares the efficacy and side effects of omeprazole and regular- and
      double-dose nizatidine in the treatment of duodenal ulcers. Duodenal ulcer
      healing rates in these three groups (omeprazole, 20 mg qd; nizatidine, 300 mg hs
      and 600 mg hs) were 81.8%, 19% and 30%, respectively, after two weeks of therapy;
      and 90.5%, 70% and 84.2%, respectively, after four weeks of treatment. Omeprazole
      had a significantly better healing rate than nizatidine, 300 mg or 600 mg, after
      two weeks of treatment (p < 0.01), but not after four weeks of treatment.
      Omeprazole relieved the ulcer pain sooner than nizatidine (p < 0.05). Smoking
      decreased the duodenal ulcer healing rate in the omeprazole group, but not in the
      nizatidine groups. Clinical features, such as sex, age, alcohol consumption,
      ulcer size, past history of upper gastrointestinal bleeding and duration of
      peptic ulcer history, did not collate with the healing rate. Patients with double
      dose nizatidine did not show any benefits over those with a regular dose in this
      study. Adverse effects were minor, and there were no significant changes in
      biochemistry after therapy in these three groups of patients.

PMID- 1362120
TI  - In vitro perfusion study of the human placenta at term: preliminary results.
AB  - Dual perfusion of the human placental lobule in vitro is a useful method for
      studying the transfer of molecules across the placenta, including the transfer of
      endogenous substances and xenobiotics. To establish the first model of in vitro
      placental dynamic study in our country, we used a dual recirculating perfusion
      system modified from that described by Miller et al. A placental lobule without
      tears or gross lesions was chosen. Both the fetal and maternal sides of the
      placenta were perfused with Medium 199 in addition to heparin, glucose, dextran
      and antibiotics. Perfusate samples were obtained periodically and analyzed for
      blood gas, glucose, lactate, human placental lactogen (hPL) and human chorionic
      gonadotropin (hCG). The stability of this human placental lobule preparation
      during 10 hours of perfusion was reflected by the stability of the arterial
      pressure and by the constant volume in the fetal compartment. A constant rate of
      oxygen was delivered by the maternal circulation system, and a steady rate of
      oxygen was gained by the fetal circulation system. Neither oxygen nor glucose
      consumption by the tissue was significantly reduced during the period of
      perfusion. The releasing rates of hCG and hPL did not change significantly during
      perfusion. The development of this dual perfusion system for the human placenta
      can provide for the study of placental hemodynamics and transplacental transport
      in perinatal medicine in our country.

PMID- 1362121
TI  - Binding and growth-stimulation of cervical cancer cell lines by prolactin.
AB  - Two cervical cancer cell lines CC7-T and Si-Ha were employed to observe the
      relationship between cervical cancer and prolactin. By immunocytochemical and
      indirect immunofluorescent assays using two prolactin monoclonal antibodies PRL
      149 and PRL-151, both cell lines with added prolactin (10 ng/mL) were noted to be
      positive for PRL-151, but negative for PRL-149. The control cell lines from
      ovarian cancer and the myeloma lines were both stained negative. By using MTT (3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, it was noted
      that CC7-T and Si-Ha grew better in the presence of various added concentrations
      of prolactin, ranging from 0.1 to 1,000 ng/mL, suggesting that prolactin may
      enhance the growth of cervical cancer. The degree of stimulation appears to
      depend on cell differentiation. However, prolactin levels in the cultured
      supernatant were undetectable by the enzyme immunoassay (EIA) method. We
      postulate that prolactin can bind and stimulate the growth of some cervical
      cancer cell lines, probably through the prolactin receptor rather than by
      autocrine regulation.

PMID- 1362122
TI  - Streptococcus bovis endocarditis associated with colonic adenocarcinoma: report
      of a case.
AB  - Streptococcus bovis (S. bovis) endocarditis has been increasing over recent
      decades, especially among the senile population. A 74-year-old man presented with
      intermittent fever for two months. He had a past history of aortic dissection and
      underwent a Bentall operation one year before admission. A Janeway lesion was
      noted on his right hand and six blood cultures grew S. bovis. He was treated with
      penicillin-G, 3 microU intravenously, every six hours, and became afebrile three
      days later. A colonofiberoscopy was carried out despite the absence of any
      gastrointestinal symptoms, and a 2 x 2 cm mass was found at the cecum, with
      pathologic proof of adenocarcinoma. The patient died from a massive intracranial
      hemorrhage on the 23rd hospital day. Review of the literature revealed an
      intimate association between S. bovis bacteremia (or endocarditis) and underlying
      colonic neoplasia. Failure to be aware of the possible consequences of this
      combination may lead to detrimental patient prognosis. We strongly advise that
      every patient presenting with bacteremia or endocarditis due to this organism,
      even if they are free from gastrointestinal symptoms, should undergo a thorough
      lower gastrointestinal investigation to rule out colonic neoplasia.

PMID- 1362123
TI  - Multiple cerebral aneurysms in a child with cardiac myxoma.
AB  - Neurologic involvement is not uncommon in cardiac myxoma, yet its association
      with multiple cerebral aneurysms is rare, especially in children. We describe a
      patient with left atrial and ventricular myxoma, who otherwise lacked cardiac
      symptomatology and did not exhibit auscultatory, roentgenologic, or electro
      cardiographic evidence of heart disease. The clinical presentation was a sudden
      attack of a cerebrovascular occlusive disorder. Multiple fusiform aneurysms at
      the frontal and parietal branches of the left anterior and middle cerebral
      arteries were demonstrated on cerebral angiograms. The myxomas were surgically
      removed and the patient improved.

PMID- 1362124
TI  - Cardiac tamponade resulting from recurrent small-cell carcinoma of the uterine
      cervix temporarily responding to CE/CAV chemotherapy: report of a case.
AB  - A case of recurrent small-cell carcinoma of the uterine cervix, initially
      presenting with cardiac tamponade, is reported. After pericardiotomy, the patient
      was treated with an alternating combination of chemotherapy, which included
      cisplatin plus etoposide (CE) and cyclophosphamide, adriamycin plus vincristine
      (CAV). A partial response, with relief of a cough and diminishing metastatic
      pulmonary lesions, was noted from serial chest roentgenographs after the initial
      three cycles of chemotherapy. The patient did not receive any further treatment
      and the recurrent cough and dyspnea were noted two months later. In spite of the
      same chemotherapeutic regimen and chest radiotherapy, the patient died nine
      months after the initial diagnosis of metastasis.

PMID- 1362125
TI  - Enhancement of DNA synthesis in rat thymocytes by stimulating their muscarinic
      acetylcholine receptors.
AB  - The binding of 3H-acetylcholine (ACh) to acetylcholine receptors (AChRs) on rat
      thymocytes was examined and found to be inhibited by the treatment with several
      antagonists against nicotinic and muscarinic AChRs. This result suggested that
      thymocytes have AChRs with different affinity, and bear both nicotinic and
      muscarinic AChRs on their surfaces. To make clear the functional significance of
      the AChRs, DNA synthesis of the thymocytes stimulated with ACh was examined. 3H
      thymidine uptake of thymocytes was significantly increased when the cells were
      stimulated with ACh or another cholinergic agonist. The increment of DNA
      synthesis caused by ACh in thymocytes was not reduced by treatment with nicotinic
      antagonists, but was decreased by treatment with any of the muscarinic
      antagonists. Concentration of the intracellular second messengers, inositol 1,4,5
      triphosphate (IP3) and guanosine 3',5'-cyclic monophosphate (cGMP) was also made
      higher by ACh stimulation. It is discussed that the enhancement of intracellular
      IP3 and cGMP concentrations after stimulation of muscarinic AChRs appears to be
      related with the increment of thymocyte DNA synthesis.

PMID- 1362126
TI  - PCR-based approaches for detection of mutated ras genes.

PMID- 1362127
TI  - Modeling of heteroduplex formation during PCR from mixtures of DNA templates.
AB  - We have investigated the capability of PCR to amplify a specific locus from each
      template in a mixture of allelic DNAs. Modeling experiments employed a 300-bp
      HOX2B segment as target and utilized, as distinct template "alleles," genomic
      DNAs from 1 human and from 2 chimpanzees known to differ in sequence at the
      target. Two modes were used: (1) mixtures of PCR products that had been
      previously amplified individually from a single template and (2) PCR
      amplification en masse from composite human/chimpanzee genomic DNA templates.
      Products generated by either mode were separated by denaturing gradient gel
      electrophoresis (DGGE). Detection of a "trace" allele mixed with a "dominant" one
      was possible by simple ethidium bromide staining of the gel up to a sensitivity
      of 1 part in 20. A balanced mixture was represented by 5:5 and 4:3:3 mixtures of
      allelic PCR products or genomic templates; an uneven mixture of dominant and
      trace alleles, by 9:1 and 8:1:1 mixtures. For 5:5, two homoduplex bands and two
      heteroduplex bands of equal intensity were generated. For 9:1, the trace
      homoduplex disappears whereas the two heteroduplexes are easily visible. For
      8:1:1, four heteroduplexes and one homoduplex were observed; homoduplexes and
      heteroduplexes formed from the trace alleles were not visible. These experiments
      demonstrate that PCR can amplify mixed allelic templates in direct proportion to
      the stoichiometric fraction of each template. Trace species are captured as
      heteroduplexes with the most abundant species and are clearly displaced on
      denaturing gradient gels from the dominant homoduplex species. Our analytical
      studies can be applied to analysis of sequence variants in DNA collected from
      cancerous or infected tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362128
TI  - Cystic fibrosis genotyping by direct PCR analysis of Guthrie blood spots.
AB  - In the United States the most common cystic fibrosis (CF) alleles known are F508,
      G551D, G542X, R553X, and N1303K. These mutations comprise approximately 85% of
      U.S. CF alleles, and their detection along with analysis of XV-2C and KM-19
      restriction fragment length polymorphisms (RFLPs) can enable the determination of
      CF status. To facilitate studies for determining CF carrier status, we developed
      methods to detect each of these mutations and RFLPs by direct PCR amplification
      of dried blood spots collected on newborn screening (Guthrie) cards. Following
      collection, samples were protected from contamination by individual plastic bags.
      One-mm2 segments of filter paper were added directly to 100-microliters PCR
      reactions containing 1/16 mM spermidine. Three initial cycles at 96 degrees C,
      then 55 degrees C, for 3 min were performed to free DNA and minimize inhibition
      by other related materials. Next, 1 unit of Taq polymerase was added and a 2-min
      extension was carried out at 72 degrees C, followed by 33 amplification cycles
      using denaturing, annealing, and extension temperatures and times optimal for
      each primer set. Then, 35 microliters of each reaction was run on 8% acrylamide
      gels directly or 1% agarose gels following digestion; genotypes were inferred by
      ethidium bromide staining of gels. Guthrie blood spots of 250 CF probands and
      their parents were screened and the frequencies of all five mutations as well as
      the XV-2C KM-19 RFLP haplotypes were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362130
TI  - The preferred treatment for subdural empyema.

PMID- 1362129
TI  - Expression, purification, and characterization of Bacneu. A soluble protein
      tyrosine kinase domain encoded by the neu-oncogene.
AB  - To further characterize the structure and regulation of the tyrosine kinase
      encoded by the rodent neu oncogene, its cytoplasmic tyrosine kinase domain has
      been expressed as a soluble protein, called Bacneu, in Sf9 insect cells, using
      the baculovirus expression system. Expression of Bacneu was detected by
      immunoblotting with anti p185neu antisera and in vitro autophosphorylation
      analysis as early as 24 h postinfection. Maximal expression was observed at 48 h
      postinfection. The soluble kinase was purified to near homogeneity by sequential
      chromatography on DEAE-Sepharose, phosphocellulose, poly-L-lysine, and Sephacryl
      300, yielding 0.55 mg Bacneu per L of Sf9 cells (4% yield). The kinase is more
      active in the presence of Mn2+ compared to Mg2+ ions. The specific activity of
      the kinase using poly(Glu4Tyr1) as a substrate is 179 nmol/min/mg. Maximal
      incorporation of 1.4 mol of phosphate per mol of enzyme by autophosphorylation
      was found to increase the activity of the enzyme 1.5- to twofold. These results
      indicate that the Bacneu kinase is activated by phosphorylation. Therefore, it
      will be a useful reagent for characterizing the effects that phosphorylation by
      other cellular kinases and dephosphorylation by phosphatases have on its
      activity.

PMID- 1362131
TI  - Glutamate-induced inhibition of paired pulse facilitation of monosynaptic
      excitatory post-synaptic potentials in frog spinal motoneurons.
AB  - To evaluate actions of glutamate on excitatory synaptic transmission in the
      central nervous system, we examined glutamate-induced changes in the paired pulse
      facilitation of monosynaptic excitatory post-synaptic potentials evoked by
      stimulation of the lateral column fibers (LC-EPSPs) on lumbar motoneurons in the
      frog spinal cord. Glutamate (1 mM) depolarized motoneurons both in the presence
      and absence of Mg2+. In most cells perfused with Mg(2+)-free or high Ca(2+)-Mg2+
      solutions, the glutamate potential was accompanied by a reduction in peak
      amplitude of EPSPs, although the degree of change varied with the cells.
      Glutamate enhanced the EPSP amplitude in a few cells with Mg(2+)-free and high
      Ca(2+)-Mg2+ solutions, and in most cells with high Mg2+ medium. In 3/5 cells
      tested, the paired pulse facilitation of EPSPs was reduced by glutamate when the
      EPSP amplitude either increased or decreased. NMDA (50 microM), kainate (50-100
      microM), quisqualate (5-50 microM) and L-2-amino-4-phosphonobutyrate (L-AP4, 1
      mM) also decreased the facilitation in about half of the cells tested. The
      glutamate-induced decrease in the facilitation was observed in both the presence
      and absence of Mg2+ and was not affected by the concomitant application of
      glutamate and antagonists for non-NMDA or NMDA receptors, such as 6-cyano-7-nitro
      quinoxalinediones (CNQX, 60 microM) or 2-amino-5-phosphonovalerate (APV, 250
      microM). Glutamate reduced the facilitation of excitatory post-synaptic currents
      (EPSCs) recorded at a constant membrane potential under voltage clamp, when the
      EPSC amplitude either increased or decreased and when the input conductance
      either increased or decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362133
TI  - [Opioids by the regional route: from enthusiasm to reason].

PMID- 1362132
TI  - Interactive role of L-glutamate and vasopressin, at the level of the PAG area,
      for cardiovascular tone and stereotyped behaviour.
AB  - The periaqueductal gray (PAG) area may modulate cardiovascular functions and
      trigger several stereotyped behavioural responses through a mechanism mediated by
      the interaction of L-glutamate with arginine vasopressin (AVP). Moreover, only
      the NMDA- but not the non-NMDA-glutamergic subtype receptors might participate in
      the control of these neurovegetative functions also modifying the homeostasis of
      the hypothalamic-neurohypophysis system. This latter effect may be due to the
      tight connections between the PAG area neurons to the more cephalic nuclei within
      the brainstem.

PMID- 1362134
TI  - Bacterial conjugation: everybody's doin' it.
AB  - Recent evidence suggests that bacterial conjugation is ubiquitous in the
      bacterial world and that DNA transfer between different genera-kingdoms is
      possible. It has also been demonstrated that many bacterial gene transfer systems
      resemble each other at the molecular level and that others are a blend of two or
      more of these systems. Thus, in the absence of a sexual cycle, bacterial
      conjugation, along with bacteriophages, transposons, and natural transformation
      systems, forms a potent force for gene dissemination and repair in the eubacteria
      and simple eukaryotes.

PMID- 1362135
TI  - Nursing economics in Canada.

PMID- 1362137
TI  - Effects of alpidem in anxious elderly outpatients: a double-blind, placebo
      controlled trial.
AB  - The efficacy and safety of alpidem, a new anxiolytic imidazopyridine, were
      compared with those of placebo in anxious elderly patients (65-80 years) by means
      of a randomized, double-blind, parallel group study. Following a 7-day "placebo
      run-in," 40 anxious patients were randomized to receive either alpidem or
      placebo. Daily doses ranging from 75 to 150 mg (25-50 mg t.i.d.) were
      administered for 3 weeks. Hamilton Rating Scale for Anxiety (HRSA), State Trait
      Anxiety Inventory (STAI-X1), Visual Analogue Scale (VAS), and Clinical Global
      Impression (CGI) were used on days 0, 3, 7, 14, and 21 for assessing efficacy.
      Psychomotor and mnesic performances were evaluated at the same time by means of
      the Digit Symbol Substitution Test (DSST), the Grunberger's test for fine motor
      coordination, and the Hawie's test for immediate memory. Possible adverse events
      were also recorded during the five visits. The anxiolytic efficacy of alpidem was
      significantly (p < 0.01) superior to that of placebo in all the rating scales
      adopted. The anxiolytic action was clearly evident from day 7. For most of the
      patients the active dose was 25 mg t.i.d. No relevant adverse effects were
      observed in both groups. No impairment of psychomotor and mnesic performances
      could be observed in the alpidem group. Alpidem is a new interesting anxiolytic
      drug for anxious elderly patients because it appears remarkably safe and, at
      effective doses, it does not impair psychomotor performances and cognitive
      functions.

PMID- 1362136
TI  - Effect of D1 and D2 agonists in primates withdrawn from long-term treatment with
      haloperidol: the potential role of dopamine D1 receptors in dyskinesia.
AB  - The effects of dopamine (DA) D1 and D2 receptor agonists were evaluated in eight
      Cebus apella monkeys. The monkeys had previously received haloperidol for 2
      years, and five of the monkeys had developed mild oral dyskinesia. SKF 81297 (a
      full D1 agonist) induced marked oral hyperkinesia, consisting of tongue
      protrusions and licking or chewing movements, most pronounced in the monkeys with
      pre-existing oral dyskinesia. SKF 38393 and SKF 75670 (partial D1 agonists) also
      induced some oral dyskinesia, but to a lesser extent than SKF 81297, and with few
      licking movements. The partial D1 agonists, but not the full agonist, induced
      sedation. All of the D1 agonists induced grooming behavior, the full D1 agonist
      to the greatest extent. In the case of SKF 81297, the grooming was closely
      associated with the licking behavior. Quinpirole (a selective D2 agonist) and
      apomorphine (a mixed D1/D2 agonist) induced a hyperactive syndrome (nonoral
      stereotypy with rapid repetitive movements and increased arousal and locomotor
      activity). Quinpirole induced no grooming behavior and reduced pre-existing oral
      movements. The data indicate behavioral differences between D1 and D2 receptors
      and suggest that D1 receptors may be involved in the pathophysiology of some
      forms of dyskinesia syndromes.

PMID- 1362138
TI  - Prevention of myocardial infarction by nitroglycerin plus intravenous beta
      blockers.
AB  - Seven patients with ongoing angina with ST-segment elevation, refractory to oral
      nifedipine and intravenous nitroglycerin, were treated by adding intravenous beta
      blockers. Chest pain resolved in all of them in a few minutes, and myocardial
      infarction did not develop in 5 patients. We recommend this approach for patients
      to whom thrombolytics are contraindicated or have been very recently
      administered, although further investigation is needed to extend its application
      more widely. It does not preclude the use of other therapies, if considered
      necessary.

PMID- 1362139
TI  - Beta-adrenergic blockade in the thrombolytic era.

PMID- 1362140
TI  - [Alternative therapy in the acute phase of endogenous depression--antiepileptics
      and new benzodiazepines and their comparison].
AB  - The average therapeutic effect of classical tricyclic antidepressants and
      antidepressants of the second and third generation varies between 60-70%.
      Moreover, tricycklic antidepressants are associated with undesirable effects
      mostly anticholinergic and "cardiotoxic", which may be a contraindication in
      particular in patients with multiple diseases and in older age groups. The
      authors compared two new alternative therapeutic procedures, represented by new
      highly effective benzodiazepines and anticonvulsants, as regards the therapeutic
      effect and side-effects. From this comparison ensues that their general
      therapeutic effect is on average comparable with the effect of tricyclic
      antidepressants, however, in the spectrum of their undesirable symptoms the
      anticholinergic effects are absent. Recent benzodiazepines have a better effect
      on depressions where anxiety and agitation are in the foreground. Their effect on
      depressive core symptoms is more marked, as compared with anticonvulsants. The
      most frequent side-effects are fatigue, somnolence and vertigo. Anticonvulsants
      have a balanced effect in different syndromological forms of depression.
      Undesirable effects are mostly gastrointestinal. In the authors' trials it did
      not lead to hypomania.

PMID- 1362141
TI  - Role of estrogen receptor variants in the development of hormone resistance in
      breast cancer.
AB  - Recent evidence suggests that the progression to hormone resistance in some
      breast tumors is due to mutations in the estrogen receptor (ER). Various types of
      ER variants have been found in breast cancer biopsies and breast cancer cell
      lines. The ER variants include dominant-positive receptors that are
      transcriptionally active in the absence of estrogen, and dominant-negative
      receptors that are themselves transcriptionally inactive but prevent the action
      of the normal receptor. The mechanisms by which these variants cause loss of
      hormonal control is becoming clear. ER variants may be prognostic factors for
      breast cancer. By modifying the action of ER variants, it should be possible to
      develop new strategies for treatment of malignant breast disease.

PMID- 1362142
TI  - Polymerase chain reaction and its potential as a pharmacokinetic tool.

PMID- 1362143
TI  - Pulmonary pharmacology in pregnancy.
AB  - The pharmacologic treatment of any pregnant patient with a respiratory illness
      should occur only after careful consideration of the effects of altered maternal
      physiology and the potential effects on the developing fetus. Pregnancy changes
      gastrointestinal absorption of drugs, creates an increased volume of
      distribution, decreases protein binding, and increases renal excretion and
      hepatic metabolism of most drugs. These changes may necessitate variation in dose
      or dosing interval of drugs administered during pregnancy. Before administration
      of a therapeutic agent, the available animal and human data summarizing fetal
      effects should be reviewed. Most of the bronchodilators and more common
      antibiotics used for respiratory infections have been used without adverse fetal
      effects. Important exceptions do exist and certain agents should be avoided. When
      the patient expresses concern over a pharmacologic or radiologic exposure during
      pregnancy, a detailed history of the type, timing, and duration of exposure and
      genetic consultation should be obtained. Finally, drug treatment of serious
      illness in the pregnant patient should not be withheld unless the risk of the
      agent in question clearly outweighs the fetal and maternal risk of untreated
      disease.

PMID- 1362144
TI  - Acute respiratory failure in pregnancy.
AB  - Acute respiratory failure in pregnancy is an important cause of maternal and
      fetal morbidity and mortality. Causes include: ARDS, venous air embolism, beta
      adrenergic tocolytic therapy, asthma, thromboembolic disease, pneumothorax, and
      pneumomediastinum. The most common predisposing diseases for ARDS complicating
      pregnancy are sepsis, pneumonia, aspiration of gastric contents, and amniotic
      fluid embolism. Knowledge of normal maternal-fetal physiology and determinants of
      fetal oxygen delivery (uterine blood flow, placental transfer, fetal circulation)
      can help sustain normal fetal development, usually without compromising maternal
      care. The increased microvascular permeability seen in ARDS is likely mediated by
      neutrophils, proinflammatory mediators (e.g., tumor necrosis factor, interleukin
      1, arachidonic acid metabolites) and activation of the complement cascade.
      Treatment of respiratory failure in pregnancy is largely supportive, including
      mechanical ventilation, hemodynamic support, nutrition, and prophylaxis against
      thromboembolism. No specific therapy has as yet been proven effective for ARDS,
      other than treating the underlying cause. Respiratory failure from status
      asthmaticus is treated with vigorous bronchodilator therapy, high-dose
      glucocorticosteroids, magnesium sulfate, and careful ventilator management.
      Occasionally, more experimental therapies (e.g., isoproterenol infusion,
      halothane anesthesia) are indicated. Certain strategies can help prevent
      respiratory failure from aspiration of gastric contents, beta-adrenergic
      tocolytic therapy, and thromboembolic disease.

PMID- 1362145
TI  - Glutamine and glucose metabolism in bovine blood lymphocytes.
AB  - 1. Glutamine and glucose metabolism was studied in bovine blood lymphocytes
      incubated at 37 degrees C in the presence of Krebs-Ringer bicarbonate buffer (pH
      7.4) containing 1 mM [U-14C]glutamine and 5 mM [U-14C]glucose, respectively. 2.
      The major metabolic products from glutamine were ammonia, glutamate, and to a
      lesser extent, aspartate and CO2. Glucose was metabolized mainly to lactate and,
      to a lesser extent, pyruvate and CO2. These findings indicate incomplete
      oxidation of glutamine and glucose carbons in bovine blood lymphocytes. 3.
      Glucose provided three-fold greater amounts of energy to bovine blood lymphocytes
      than did glutamine on the basis of their measured end-products. Glycolysis
      accounted for 50% of glucose-derived ATP production. 4. Our findings suggest
      similar metabolic patterns of glutamine and glucose in lymphocytes between
      ruminants and non-ruminant species (e.g. rats). However, in contrast to rat
      peripheral lymphocytes, glucose, rather than glutamine, was a major energy
      substrate for bovine blood lymphocytes.

PMID- 1362146
TI  - Toward a chronotherapy of ovarian cancer. Part III: Salivary CA125 for
      chronochemotherapy by efficacy.

PMID- 1362147
TI  - Restriction fragment length polymorphisms near the islet amyloid polypeptide gene
      in Japanese subjects.
AB  - Two restriction fragment length polymorphisms (RFLPs) near the human islet
      amyloid polypeptide (IAPP) gene were examined in 50 Japanese patients with non
      insulin-independent diabetes mellitus (NIDDM) and 54 non-diabetic controls. RFLPs
      were identified with the enzymes PvuII (A1 = 21 kb and A2 = 18 kb) and BglII (B1
      = 9 kb and B2 = 7 kb). These RFLPs were in complete linkage disequilibrium with
      A1 which was in disequilibrium with B2, as was A2 with B1. Since these two RFLPs
      map to different locations in the 5'-flanking region of the IAPP gene, they are
      most likely due to changes in the sequence of the sites recognized by PvuII and
      BglII rather than to an insertion/deletion-type DNA polymorphism. There were no
      differences in the genotypic or allelic frequencies of these RFLPs between
      Japanese subjects with NIDDM and non-diabetic controls implying that these RFLPs
      do not play a major role in the development of NIDDM in this population.

PMID- 1362148
TI  - [The therapy of hyperprolactinemia].

PMID- 1362149
TI  - Non-suppressed thyroidal radioactive iodine uptake (RAIU) in thyrotoxic phase in
      a case of subacute thyroiditis with thyroid-stimulating antibodies (TSAb).
AB  - In this paper, we report a 49-year-old female with subacute thyroiditis who had
      thyroid-stimulating antibodies (TSAb) and thyroid-stimulation-blocking antibodies
      (TSBAb) in serum. Although she was in the thyrotoxic phase and TSH was suppressed
      in May, 1990, her radioactive iodine uptake (RAIU) was not suppressed (35.5%) and
      a thyroid scan disclosed a diffuse goiter with no defect. Serum assays revealed
      the presence of TSAb, but TSBAb were negative. In August, 1990, the right lobe
      became undetectable by thyroid scan when the RAIU was 20.7% with the TSH level
      remaining suppressed. At that time, TSAb were negative, while TSBAb were
      positive. When the RAIU was 31.1% in October, 1990, both thyroid lobes became
      visible and the TSH level was normalized. TSBAb became negative, and although
      TSAb reappeared it later became undetectable. These results indicate that the
      changes in the patient's thyroid scan and RAIU were attributable to the presence
      of TSAb.

PMID- 1362150
TI  - Simultaneous measurement of changes in the membrane potential and the
      intracellular Ca2+ concentration caused by somatostatin in human GH-producing
      pituitary tumor cells.
AB  - Changes in the membrane potential and the intracellular Ca2+ concentration
      ([Ca2+]i) caused by somatostatin (SRIF) were simultaneously measured in human GH
      producing pituitary tumor cells, by means of the nystatin-perforated whole cell
      clamp technique and Fura-2 AM. An application of 10(-8) M SRIF hyperpolarized the
      membrane and arrested Ca(2+)-dependent spontaneous action potentials. [Ca2+]i
      concurrently decreased during membrane hyperpolarization. When the membrane
      potential was clamped below the threshold for voltage-gated Ca2+ channels,
      [Ca2+]i decreased and SRIF did not further reduce [Ca2+]i. In cells which did not
      show spontaneous action potentials, SRIF hyperpolarized the membrane but it
      affected [Ca2+]i little. From these results it was concluded that the reduction
      in [Ca2+]i caused by SRIF was ascribed to the decrease in Ca2+ influx through
      voltage-gated channels during membrane hyperpolarization. The effect of SRIF on
      the voltage-gated Ca2+ channel current was also examined under the perforated
      whole cell clamp. SRIF (10(-8) M) inhibited the Ca2+ channel current to 80.8 +/-
      15.4% (n = 5) of the control. Because SRIF-induced inhibition of the voltage
      gated Ca2+ channel current was not prominent, it was considered that membrane
      hyperpolarization is the major cause of the reduction in [Ca2+]i in human GH
      producing cells.

PMID- 1362151
TI  - Ventricular function and pressure -- volume analysis. The role of conductance in
      cardiology. Nuernberg, Germany, 16-17 August 1991.

PMID- 1362153
TI  - Back to basics in the management of arrhythmias -- New approaches and rational
      therapy. Symposium proceedings. Barcelona, Spain, 30 August 1992.

PMID- 1362152
TI  - Aortic input impedance in mild to moderate chronic congestive heart failure: lack
      of interrelation with neurohormonal activation.
AB  - Patients with chronic congestive heart failure (CHF) have activated neurohormonal
      systems, which may induce vasoconstriction. In addition, the arterial wall sodium
      content may increase and could have direct trophic effects on vascular smooth
      muscle cells. These mechanisms might elevate left ventricular (LV) pulsatile
      load. We measured aortic input impedance to find out the LV pulsatile load and
      neurohormonal activation in 20 patients with mild to moderate chronic CHF.
      Cardiac index (2.2 +/- 0.3 l.min-1 x m-2) and LV ejection fraction (38 +/- 4%)
      were reduced, pulmonary wedge pressure was elevated (21 +/- 2 mmHg). Plasma
      norepinephrine levels (462 +/- 62 pg.ml-1), plasma renin concentration (12 +/- 4
      ng.AI.ml-1h-1), plasma levels of atrial natriuretic peptide (408 +/- 64 pg.ml-1)
      and, to a slight degree, plasma arginine vasopressin (1.1 +/- 0.3 pg.ml-1) were
      increased. Characteristic impedance, Zc, was within the normal range (80 +/- 6
      dyn.s.cm-5) and showed no significant correlation with the degree of
      neurohormonal activation (r-values: -0.05 to -0.35). CONCLUSIONS: Our data
      demonstrate that in early stages of CHF stimulation of the neurohormonal systems
      does not significantly elevate LV pulsatile load; therefore there is no
      substantial alteration in the physical properties of the great arteries.

PMID- 1362154
TI  - Impact of primary surgical approach in the management of the impalpable testis.
AB  - There is no univoque opinion about the place of preoperative studies in non
      palpable testes. During a 6.5-year period, we operated on 296 impalpable testes
      in prepubertal boys. A combined inguinal-abdominal approach was used in all cases
      verifying the eventual abdominal testis and its exact vascular anatomy before any
      manipulation of the cord was undertaken. Forty-five testes (15.2%) were
      canalicular, 142 (48%) were abdominal, 5 (1.7%) dysgenetic and 104 (34.1%) absent
      (agenesis or vanishing testis). Of the abdominal testes, 122 underwent a standard
      orchidopexy in dartos pouch, 11 a staged repair, 8 a Fowler-Stephens operation
      and 1 orchiectomy. All means of investigation for impalpable testes are either
      unreliable, too expensive or too invasive for routine use, and in most cases, a
      surgical exploration has to be performed anyway. The primary surgical approach
      has the most favorable cost/benefit ratio, being diagnostic and therapeutic at
      one time. Provided the exploration is performed correctly, all the advantages of
      previous laparoscopy can be achieved with surgery alone.

PMID- 1362155
TI  - Correlation between the expression of P-glycoprotein and multidrug-resistant
      phenotype in transitional cell carcinoma of the urinary tract.
AB  - The expression of a multidrug-resistant (MDR) gene product, P-glycoprotein, was
      examined immunohistochemically in 41 transitional cell carcinomas (TCCs) of the
      urinary tract. In 23 of these, chemosensitivity to adriamycin (ADM) and
      vinblastine (VBL) was also assessed by a microtiter succinate dehydrogenase
      inhibition test and the correlation between the expression of P-glycoprotein and
      MDR phenotype was investigated. P-glycoprotein was detected in 13 (72.2%) of the
      18 untreated TCCs of the upper urinary tract (UUT), 6 (31.6%) of the 19 untreated
      TCCs of the bladder, and all of the 4 TCCs treated with M-VAC chemotherapy,
      respectively. Fourteen (87.5%) of the 16 TCCs with a positive expression of P
      glycoprotein were resistant to ADM and VBL, whereas all of the 4 TCCs sensitive
      to both drugs were negative in the expression of P-glycoprotein. The succinate
      dehydrogenase activity of TCCs with a positive expression of P-glycoprotein was
      significantly higher than that of TCCs with a negative expression of P
      glycoprotein (P < 0.05). Thus, there was a good correlation between the
      expression of P-glycoprotein and MDR phenotype in the chemosensitivity test.
      These results suggest that intrinsic MDR exists in some TCCs of the urinary
      tract, particularly UUT, and that the immunohistochemical investigation of P
      glycoprotein may be useful for predicting the MDR phenotype in TCCs of the
      urinary tract.

PMID- 1362156
TI  - Early diagnosis of the multiple endocrine neoplasia type 2 syndrome: consensus
      statement. European Community Concerted Action: Medullary Thyroid Carcinoma.
AB  - The diagnosis of medullary thyroid carcinoma by biochemical and genetic testing
      is possible in families with multiple endocrine neoplasia type 2. At an early
      stage total thyroidectomy usually cures the patient. As the clinical penetrance
      of the autosomal dominant, transmitted, multiple endocrine neoplasia type 2 gene
      is not complete, family screening is indicated for every new patient who presents
      with apparently sporadic medullary thyroid carcinoma. Problems related to a
      screening programme and early diagnosis have led the members of the European
      Community Concerted Action: Medullary Thyroid Carcinoma group to formulate a
      consensus on biochemical and genetic screening. For biochemical screening,
      measurement of basal and pentagastrin and/or calcium stimulated serum levels of
      calcitonin by radioimmunoassay are essential starting at the age of three and
      continuing annually until 35 years of age. Furthermore, annual screening for
      pheochromocytoma by measuring the urinary excretion of catecholamines and for
      hyperparathyroidism by serum calcium determination is indicated. Genetic
      screening using linked markers can be done with a 95% accuracy in informative
      families when DNA is available from at least two family members proven to be
      affected. Biochemical screening can thus be reserved for gene carriers, while
      those at low risk can be reassured. Combined biochemical and genetic screening
      for multiple endocrine neoplasia type 2 is important and effective for the cure
      of medullary thyroid carcinoma.

PMID- 1362157
TI  - New horizons in the pathogenesis of coronary heart disease.

PMID- 1362158
TI  - Noradrenergic mediation of spinal antinociception by 5-hydroxytryptamine:
      characterization of receptor subtypes.
AB  - The present study examined the involvement of spinal noradrenergic mechanisms in
      spinal antinociception by the 5-hydroxy-tryptamine (5-HT) receptor-selective
      agonists CGS 12066B (5-HT1B; 7-trifluoromethyl-4(4-methyl-1-piperazinyl)
      pyrrolo[1,2-a]quinoxaline), TFMPP (5-HT1C; M-trifluoromethylphenyl-piperazine)
      and DOI (5-HT2; 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) using the rat hot
      plate test. Effects of alpha-adrenoreceptor antagonists (phentolamine,
      yohimbine), the adrenergic neurotoxin 6-hydroxydopamine, and the selective
      noradrenergic uptake blocker desipramine were determined. CGS 12066B, TFMPP and
      DOI produced dose-related antinociception. The antinociceptive effect of each
      agent was reduced by pretreatment with both phentolamine and yohimbine (15-60
      micrograms). Pretreatment with 6-hydroxydopamine (100 micrograms, intrathecal)
      for 7-10 days, which reduced spinal cord levels of noradrenaline by 87%,
      inhibited the action of TFMPP (and 5-HT), but not CGS 12066B or DOI. Pretreatment
      with desipramine (25 mg/kg, systemic) potentiated the action of TFMPP but not CGS
      12066B or DOI (or 2-methyl-5-HT). These results suggest that antinociception by
      TFMPP is dependent on release of endogenous noradrenaline from the spinal cord,
      while that produced by CGS 12066B and DOI is not. As TFMPP exhibits a close
      similarity to 5-HT in these experiments, the 5-HT receptor subtype being
      activated to induce noradrenaline release may either be a 5-HT1C or a 5-HT1S
      subtype. Other mechanisms account for the observed blockade of the action of CGS
      12066B and DOI by alpha-adrenoreceptor antagonists.

PMID- 1362159
TI  - 5-HT2 receptors exert a state-dependent regulation of dopaminergic function:
      studies with MDL 100,907 and the amphetamine analogue, 3,4
      methylenedioxymethamphetamine.
AB  - The highly selective 5-HT2 receptor antagonist, MDL 100,907, was used to explore
      the role of serotonin in the stimulation of dopaminergic function produced by the
      amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA). MDL 100,907
      blocked MDMA-stimulated dopamine synthesis in vivo without affecting basal
      synthesis. The long-term deficits in 5-HT concentrations believed to be a
      consequence of MDMA-induced dopamine release were also blocked by MDL 100,907
      over the same dose range. In vivo microdialysis confirmed that 5-HT2 receptor
      blockade with MDL 100,907 attenuated MDMA-induced increases in extracellular
      concentrations of striatal dopamine. In contrast to its effect on MDMA-induced
      synthesis, MDL 100,907 did not alter dopamine synthesis stimulated by haloperidol
      or reserpine. In vivo dopamine release produced by haloperidol was also
      unaffected by MDL 100,907. The results suggest a permissive role for 5-HT2
      receptors in the activation of the dopamine system which occurs during states of
      high serotonergic activity or during conditions of elevated dopamine efflux with
      high D2 receptor occupancy.

PMID- 1362160
TI  - Suppression by cetirizine of pleurisy triggered by antigen in actively sensitized
      rats.
AB  - The efficacy of cetirizine in comparison with meclizine, another piperazine H1
      receptor antagonist, in rat pleurisy caused by allergen or autacoid was
      investigated. Sensitization was achieved by subcutaneous injection of a mixture
      of ovalbumin and aluminium hydroxide. Fourteen days later, the animals were
      challenged with an intrathoracic injection of ovalbumin (12 micrograms/cavity),
      which caused drastic mast cell degranulation, followed by pleural oedema and
      leucocyte influx. Cetirizine and meclizine (2.5-30 mg/kg i.p.), 1 h before
      challenge, inhibited the exudatory response evoked by antigen, under conditions
      where neutrophil and eosinophil accumulation was affected only by the former.
      When administered intrathoracically 22 h after allergen, i.e. using a curative
      approach, cetirizine (15 micrograms/cavity) drastically reduced the pleural
      eosinophilia noted 24 h post-challenge, indicating that this drug can reverse an
      already established eosinophilia. Cetirizine (15 mg/kg i.p.) also restored, to
      about 39% (P < 0.001), the number of uninjured mast cells recovered from the
      pleural cavity following allergen stimulation. In normal rats, cetirizine (5-15
      micrograms/cavity) completely inhibited the pleural exudation elicited by
      histamine and only partially the exudation caused by 5-hydroxytryptamine or
      bradykinin, but was quite inactive against platelet-activating factor. We
      conclude that the pleural exudation triggered by allergen, vasoactive amines or
      bradykinin is clearly sensitive to cetirizine. In addition, the ability of the
      drug to interfere with pleural neutrophil or eosinophil mobilization and mast
      cell degranulation seems not to be associated with its ability to block the
      histamine H1 receptor.

PMID- 1362161
TI  - Cardiovascular effects of the 5-HT1A receptor ligand, MDL 73005EF, in conscious
      spontaneously hypertensive rats.
AB  - The effects of pretreatment with the potent and selective 5-HT1A receptor ligand,
      MDL 73005EF, on the cardiovascular responses to administration of the 5-HT1A
      receptor agonists, 8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT),
      flesinoxan and 5-methylurapidil were studied in conscious spontaneously
      hypertensive rats (SHR) and compared with those of putative 5-HT1A receptor
      antagonists. MDL 7300EF (0.1-3 mg/kg) induced a dose-dependent but transient
      decrease in mean arterial pressure (MAP). Pretreatment with doses of 1 or 3 mg/kg
      MDL 73005EF significantly inhibited the hypotensive and bradycardiac effects of 8
      OH-DPAT (0.03-1 mg/kg). Pretreatment with 1 mg/kg MDL 73005EF similarly reduced
      the hypotensive actions of flesinoxan (0.3-1 mg/kg) and 5-methylurapidil (0.1
      mg/kg). In contrast, MDL 73005EF did not significantly affect the decrease in
      blood pressure induced by administration of 0.01 mg/kg clonidine, 0.3 mg/kg
      hydralazine or 0.2 mg/kg nifedipine. The effect of 8-OH-DPAT (0.1 mg/kg) on MAP
      was also reduced by pretreatment with 1 mg/kg BMY 7378, buspirone or pindolol,
      but not NAN 190 or spiperone. BMY 7378, NAN 190, pindolol and spiperone induced a
      significant decrease in blood pressure. To rule out the possibility that the
      reduced baseline may have influenced responses to 8-OH-DPAT, we showed that
      pretreatment with the vasodilator, hydralazine (0.3 mg/kg), had no effect on the
      MAP response to 8-OH-DPAT although it significantly reduced MAP. We conclude that
      MDL 73005EF acts as a mixed agonist/antagonist at 5-HT1A receptors since it
      caused a decrease in blood pressure, but also reduced the cardiovascular
      responses to the 5-HT1A receptor agonists, 8-OH-DPAT, flesinoxan and 5
      methylurapidil.

PMID- 1362162
TI  - Effect of (+)-niguldipine on myocardial alpha 1-adrenoceptors in the rabbit.
AB  - The influence of the alpha 1A-adrenoceptor subtype-selective antagonist (+)
      niguldipine on the alpha 1-mediated positive inotropic effect was assessed in the
      isolated rabbit ventricular myocardium. (+)-Niguldipine displaced the specific
      binding of [3H]prazosin to a membrane fraction derived from rabbit ventricular
      muscle with high (Ki = 64.6 pmol/l; RH = 23%) and low (Ki = 7.08 nmol/l)
      affinity. (+)-Niguldipine displaced specific [3H]CGP-121177 binding only at very
      high concentrations (Ki = 118 nmol/l). (+)-Niguldipine at 0.1 pmol/l and higher
      shifted the concentration-response curve for the alpha 1-mediated positive
      inotropic effect downwards, but at higher concentrations (up to 10 and 100
      nmol/l) it did not cause a further shift of the curve. (+)-Niguldipine (1-100
      nmol/l) did not affect the beta-mediated positive inotropic effect and the basal
      force of concentration. (-)-Niguldipine also showed a selective inhibitory action
      on the alpha 1-adrenoceptor-mediated positive inotropic effect, but its affinity
      and potency were approximately 1-2 log units lower than those of (+)-niguldipine.
      The present results indicate that the alpha 1A-adrenoceptor subtype is involved
      in the alpha 1-mediated positive inotropic effect. (+)-Niguldipine (or (-)
      niguldipine with lower affinity) is able to antagonize selectively the cardiac
      alpha 1A-adrenoceptor-mediated positive inotropic effect. The magnitude of the
      alpha 1A-mediated inotropic effect, however, may be much less than that mediated
      by the alpha 1B-subtype in the rabbit ventricular myocardium.

PMID- 1362163
TI  - Pharmacological characterization of a 5-HT receptor in locust nervous tissue.
AB  - A 5-HT receptor in the nervous tissue of the desert locust (Schistocerca gregaria
      Forsk.) was investigated, using [3H]LSD (lysergic acid diethylamide) as the
      radioligand. [3H]LSD labels in addition a putative dopamine receptor whose
      specific [3H]LSD binding nevertheless could easily be diminished by co-incubation
      with 1 microM dopamine. The binding site was characterized by a KD of 1.64 nM,
      and a maximal concentration of binding sites of 79.8 fmol/mg protein.
      Pharmacological investigation revealed a relatively low affinity for the putative
      natural agonist, serotonin (KI = 0.209 microM). In contrast to the high affinity
      of classical serotonergic antagonists (e.g. dihydroergotamine or (+)-butaclamol)
      substances with subtype specificity such as 8-OH-DPAT (8-hydroxyl-1-(N,N
      dipropyl)-aminotetralin) or ketanserin have only moderate affinities.
      Quantitative comparison of the pharmacological data demonstrated that there is
      obviously no pharmacological homology with vertebrate 5-HT receptors
      characterized so far. The only receptors with a close pharmacological
      relationship to the 5-HT receptor of locusts are the 5-HTdro1 receptor expressed
      in Drosophila nervous tissue and a 5-HT receptor in snail nervous tissue which
      might be homologous to that of locusts. The 5-HT receptor investigated, was shown
      to be G-protein-coupled, as addition of stable GTP analogues or depletion of Mg2+
      ions from the incubation medium led to agonist-specific lowering of the affinity.

PMID- 1362165
TI  - Continuous Cell Lines -- An International Workshop on Current Issues.
      Proceedings. Bethesda, Maryland, March 20-22, 1991.

PMID- 1362164
TI  - Prognostic significance of immunohistochemical c-erbB-2 proto-oncogene expression
      and nuclear DNA content in human breast cancer.
AB  - Immunoreactivity of the c-erbB-2 proto-oncogene product and nuclear DNA content
      were assessed in specimens from 211 breast cancer patients with a mean follow-up
      of 16 years (range 13-19 years). A routine immunoperoxidase technique was used
      and cytometrical DNA assessments were performed on cytodiagnostically identified
      tumour nuclei, using image analysis. C-erbB-2 cell membrane staining was observed
      in 29% of the cases and was found to be related to tumour size (P = 0.02),
      histopathological grade (P = 0.02) and nuclear DNA content (P < 0.01). In
      univariate analysis immunohistochemical c-erbB-2 expression was of prognostic
      significance among node-positive patients (P = 0.02), but not among women with
      node-negative disease. This prognostic ability was reduced by multivariate
      analysis and was no longer significant. In contrast, nuclear DNA content was
      significantly related to distant recurrence-free survival even in multivariate
      analysis after adjustment for nodal status and tumour size (P < 0.01). In
      conclusion, the findings of the present study indicate that c-erbB-2 expression
      is of limited prognostic value in a subgroup of patients, whereas nuclear DNA
      content seems to provide significant prognostic information even in node-negative
      patients.

PMID- 1362166
TI  - Diabetes and frontiers of research. Report from the 3rd JDF World Conference on
      Diabetes Research. Monte Carlo, Monaco, 8-10 March 1992.

PMID- 1362167
TI  - [Beta blocking agents in the treatment of dilated cardiomyopathy: review of the
      literature and clinical experience with 67 patients].
AB  - BACKGROUND: Several reports suggest that chronic beta blockade, most often with
      the beta 1 selective agent metoprolol, may improve hemodynamic and clinical
      function in patients with idiopathic dilated cardiomyopathy. However, controlled
      trials are limited and some studies have not shown beneficial effects in short
      term trials. Mechanisms of effectiveness are still debated and probably concern
      the capacity to avoid toxic myocardial damage by catecholamines, to induce
      receptor up-regulation, to contribute to the control of arrhythmias, to improve
      diastolic relaxation and other mechanisms. METHODS: After a revision of the
      literature, a preliminary clinical experience with metoprolol in dilated
      cardiomyopathy diagnosed according to the WHO definition is reported. Sixty-seven
      patients symptomatic for congestive heart failure or with complex ventricular
      arrhythmias associated with severe left ventricular dysfunction were submitted to
      test dose with metoprolol 5 mg bid for 2-7 days. All patients were completely
      studied, including coronary angiography and endomyocardial biopsy to exclude
      ischemic heart disease and active myocarditis. Four pts (6%) did not tolerate the
      first test dosage of metoprolol and twenty-two patients were excluded from
      analysis because of inadequate follow-up or because they were enrolled in an
      international trial. Forty-one patients underwent long-term treatment with
      metoprolol at a final mean dosage of 150 mg a day (range 50-200 mg) and are
      presently analyzed. The dosage was gradually increased during the first seven
      weeks. RESULTS: After 6 +/- 2 months and 12 +/- 2 months, 34 patients were stable
      or ameliorated (Group 1) and experienced an overall significant improvement of
      functional class (all pts in class I-II NYHA), of left and right ventricular
      ejection fraction (from 28 +/- 8.8% to 35.8 +/- 13.7% to 33.2 +/- 12.3% and from
      38.6 +/- 11.8% to 42.4 +/- 5.8% to 45.2 +/- 12.2% respectively), of clinical
      signs of congestive heart failure, of cardiothoracic index, of left ventricular
      diameters and of arrhythmic pattern. Furthermore, the rate of ventricular
      couplets > 20/24h and of non-sustained ventricular tachycardia changed
      respectively from 46% and 54% to 4% and 21% at 12 +/- 2 months. None in Group 1
      died nor is any waiting for heart transplantation. Eleven patients (Group 2) did
      not tolerate the drug acutely (4 pts) or deteriorated during the first 6 +/- 2
      months (7 pts) of the treatment. In this group a worsening or an insignificant
      variation of all clinical and instrumental parameters was observed. During follow
      up four patients of this group underwent heart transplantation (one died shortly
      after the operation because of infective complications), one died while waiting,
      two are currently waiting for heart transplantation, and three are still in heart
      failure (class III NYHA). No cases of sudden death occurred in any group of
      patients (15 pts with follow-up > 12 mo). CONCLUSIONS: Our uncontrolled study
      seems to confirm the beneficial effect of betablockers in a subgroup of patients
      with idiopathic dilated cardiomyopathy. The characterization of responders to
      this therapy is still undefined and will constitute the aim of future analyses.

PMID- 1362168
TI  - [Expression of the P-glycoprotein in the digestive tract and the liver.
      Implication in cellular physiology].

PMID- 1362169
TI  - Evidence for the kidney as an important source of 5'-monodeiodination activity
      and stimulation by somatostatin in Oreochromis niloticus L.
AB  - Radioimmunoassay of 3,5,3'-triiodothyronine (T3) and thyroxine (T4) in the
      thyroidal region of mature male Oreochromis niloticus revealed stores of T4 but
      negligible levels of T3, yielding a very low T3/T4 ratio (0.3%). 5'-Deiodination
      (5-D) of T4 into T3 was examined in liver and kidney homogenates in vitro by
      radioimmunoassay of T3 with T4 as substrate. In both organs, the 5'-D activity
      was temperature dependent: at 4 degrees C, T3 production was below the level of
      detection and maximal in both tissues at 37 degrees C; and at 45 degrees C, the
      enzymatic activity was reduced. T3 production seemed to reach a plateau after 60
      min of incubation. The reaction required exogenous thiol cofactor
      (dithiothreitol) and was inhibited partially or completely by propylthiouracil
      depending on the concentrations used. Hepatic and renal 5'-D activities were
      stimulated by somatostatin (SRIF) within 4 hr, but a subsequent increase in
      plasma T3 was observed only when SRIF was injected together with T4, while the
      magnitude of rT3 production decreased. It is concluded that almost all the
      circulating T3 is provided by peripheral T4 to T3 conversion since T3 RIA in
      thyroidal follicles demonstrated insignificant T3 production. The kidney may
      contain the large part of the functional deiodinase which converts T4 into T3. As
      in mammals and unlike in other fishes, there is not only 5'-D activity, but also
      5-D activity, and both may be influenced by SRIF.

PMID- 1362170
TI  - Regulation of nitrogen fixation in Azospirillum brasilense Sp7: involvement of
      nifA, glnA and glnB gene products.
AB  - The expression of nifA-, niH- and nifB-lacZ fusions was examined in different
      mutants of Azospirillum brasilense. Mutations in nifA, glnA and glnB severely
      impaired the expression of nifH- and nifB-lacZ fusions. By contrast, a nifA-lacZ
      fusion was not affected in a nifA or a glnB background and was only partially
      impaired in glnA mutants. It is proposed that in A. brasilense, the PII protein
      and glutamine synthetase are involved in a post-translational modification of
      NifA.

PMID- 1362171
TI  - The autolytic ('suicidase') system of Enterococcus hirae: from lysine depletion
      autolysis to biochemical and molecular studies of the two muramidases of
      Enterococcus hirae ATCC 9790.
AB  - Autolysis of Enterococcus hirae ATCC 9790 is the result of the action of
      endogenous enzymes that hydrolyze bonds in the protective and shape-maintaining
      cell wall peptidoglycan. It is thought that these potentially suicidal enzymes
      play a positive role(s) in wall growth and division and are expressed as
      autolysins when cell wall assembly and/or repair are inhibited. E. hirae
      possesses two potentially autolytic enzymes, both of which are muramidases.
      Although they hydrolyze the same bond as hen egg-white lysozyme, both are high
      molecular-mass, complex enzymes. Muramidase-1 is synthesized as a zymogen,
      requiring protease activation. It is a glucoenzyme that is also multiply
      nucleotidylated with an unusual nucleotide, 5-mercaptouridine monophosphate.
      Muramidase-2 is almost certainly a product of a separate gene. The deduced amino
      acid sequence of a cloned gene for extracellular muramidase-2 showed several
      unusual features. It appears to be a two-, or perhaps three-domain protein with a
      putative glycosidase-active site near the N-terminal end and six 45-amino-acid
      long repeats at the C-terminal end which are presumed to be involved with high
      affinity binding to the insoluble peptidoglycan substrate. Muramidase-2 binds
      penicillin with low affinity. The presence of several amino acid groupings
      characteristic of serine-active site beta-lactam-interactive proteins is
      consistent with the possible presence of a penicillin-binding, third domain.
      Indirect evidence consistent with a role(s) for these enzymes in cell wall growth
      and division has been obtained. However, proof of such role(s) awaits modern
      genetic, molecular, and biochemical analyses.

PMID- 1362172
TI  - Penetration of fimbriate enteric bacteria through basement membranes: a
      hypothesis.
AB  - A mechanism for penetration of basement membranes by Escherichia coli is
      presented. The mechanism is based on the ability of the S fimbriae of meningitis
      associated E. coli to bind to vascular endothelium and choroid plexuses in brain
      and to basement membranes. On the other hand, the S and the type 1 fimbriae of E.
      coli immobilize plasminogen and tissue-type plasminogen activator; this process
      generates proteolytic plasmin activity on the surface of fimbriate cells. Our
      hypothesis is that bacterium-bound plasma activity, directed to basement
      membranes through fimbrial binding, promotes bacterial penetration through
      basement membranes.

PMID- 1362173
TI  - Bacterial flagellar diversity and significance in pathogenesis.
AB  - Bacterial flagella are structurally diverse, ranging from the thoroughly
      investigated model examples found in Escherichia coli and Salmonella typhimurium
      to the more exotic sheathed flagella of, for example, Helicobacter pylori, and
      the complex multi-flagellin endoflagella found in many spirochaetes. We summarize
      some of the emerging structural and genetic findings relating to these more novel
      flagellar types, and outline their possible significance in the pathogenicity of
      some medically important bacteria.

PMID- 1362174
TI  - Structural analysis and biological significance of the cell wall lytic enzymes of
      Streptococcus pneumoniae and its bacteriophage.
AB  - The development of an appropriate technique for the identification of autolysin
      defective mutants of pneumococcus has been a fundamental step to carry out
      studies on the molecular characteristics of the lytic enzymes of Streptococcus
      pneumoniae and its bacteriophage. Our results show that the principal
      pneumococcal autolysin (an amidase) is responsible for the separation of the
      daughter cells at the end of the cell division. On the other hand, this system
      provides a reliable experimental model to support the extended idea concerning
      the modular organization of most proteins. The comparative analyses of the
      deduced amino acid sequences of these enzymes, as well as the construction of
      functional chimeric phage-bacterial enzymes, demonstrate that the C-terminal
      domain, which contains a large number of repeated amino acid motifs, is the
      substrate-binding domain, whereas the N-terminal domain provides enzymatic
      specificity. We propose that the pneumococcal lytic enzymes have evolved by
      modular exchange providing examples of the types of novel genes that the bacteria
      or the phage might create to allow them to become adapted to new environmental
      situations.

PMID- 1362175
TI  - [Hygienic evaluation of the work of technical school students on the video
      display terminals].
AB  - Psychologic and hygienic examination of students working on display calculating
      complexes (DCC) DCC-2 and DCC-3 during the extra study time revealed the features
      of their functional status caused by the DCC design and work schedule. Positive
      role of eye exercises during the work was stressed. 6-hours duration of students'
      work was considered as unfavourable. The duration of work must be reduced to 3
      hours, prophylactic measures (eye and physical exercises) are to be added.

PMID- 1362176
TI  - Inside Hemophilia: Milestones in Hemophilia and von Willebrand's Disease in the
      Last 25 Years. Conference proceedings from the 4th International Meeting on
      Hemophilia. Madrid, Spain, January 23-24, 1992. Dedicated to Dr. J. Martin Villar
      in his retirement.

PMID- 1362177
TI  - AIDS and hemophilia: experience in the La Paz Hemophilia Center.
AB  - 435 hemophiliacs are usually being attended in the La Paz hemophilia Center
      (Madrid, Spain). 257 (59%) of these patients have been infected by the human
      immunodeficiency virus (HIV-1) because of human plasma derivate substitution
      therapy. The infection has been more frequent among the severely affected
      patients and among the most treated patients. 82% of the infected patients are
      between 14 and 40 years old. By December 1991, 95 (37%) of 257 seropositive
      patients have developed full-blown AIDS. The most frequent opportunistic
      infection they had suffered was esophageal candidiasis. Looking for an evolution
      marker, we can point that the patients older than 35 years with CD4 levels below
      200/mm3 had the worst prognosis. There was no difference in the evolution among
      the patients aged below 17 and those aged between 17 and 35 years. The amount of
      concentrate used between 1980 and 1984 did not hold any relation to the
      evolution. 49 patients (51%) of the 95 suffering from AIDS had died by December
      1991. The evolution to the death was unrelated to the patient age, CD4 lymphocyte
      levels, and amount of substitution therapy. In our opinion, the most valuable
      marker could be the kind of opportunistic infection or tumor the patient suffers
      from. Finally, Retrovir has demonstrated to be useful in increasing the survival
      rate of the patients, but after 36 months of treatment, only 33% of those AIDS
      patients who began taking it remained alive. Retrovir was also used in
      asymptomatic patients, and during an average period of time of 15 months, a
      lesser bone marrow toxicity and a stabilization in CD4 lymphocyte levels could be
      observed, but this was unable to modify the disease progression in those patients
      who presented circulating p24 antigen.

PMID- 1362178
TI  - Plasma protein C as a marker of hepatocellular damage in alcoholic liver disease.
AB  - The synthesis of a number of clotting factors takes place in a hepatocyte.
      Therefore, measurement of these factors in the blood have proved to be of
      additional value in the diagnosis and follow-up of liver diseases. In the present
      study we evaluated protein C level in the plasma of patients with liver cell
      damage due to chronic alcohol consumption. A decrease in plasma protein C
      concentration which correlated with clinical performance of the patients was
      found. Significant correlations between the level of protein C and antithrombin
      III, one-stage prothrombin time, factors VII and X and some biochemical tests
      reflecting liver cell damage were also stated. The obtained data indicate that
      plasma protein C level may constitute a useful marker of hepatocellular disease
      in alcoholics.

PMID- 1362179
TI  - Class I gene contraction within the HLA-A subregion of the human MHC.
AB  - Individuals expressing either the HLA-A24 or the HLA-A23 histocompatibility
      antigens have been found to possess an HLA-A class I subregion approximately 50
      kb smaller in size than those studied from individuals expressing other HLA-A
      haplotypes. This originally manifested itself as a haplotype-associated size
      variation in the NotI and MluI megabase fragments observed on pulsed-field
      electrophoresis gels after blotting and probing with HLA-A subregion-specific
      genomic probes. The contracted region falls between the HLA-A and the HLA-G class
      I genes and specifically includes the novel HLA-A-related pseudogene, HLA-H, as
      well as the adjacent deteriorated class I pseudogene, 7.0 p. The intactness of
      locus D6S128, defined by probe pMC6.7 located telomeric to the HLA-H gene,
      demonstrates that the distal rearrangement point falls within a 20-kb stretch of
      DNA separating HLA-H from pMC6.7. This extends a previous report regarding
      variation in class I gene number within the human major histocompatibility
      complex and precisely localizes the genomic residence of sequences that may
      define a recombination hot spot. Because the size variation maps to a
      recombinogenic area, its characterization may ultimately reveal important
      biological information relevant to the events that shaped the organization of the
      human HLA class I multigene family.

PMID- 1362180
TI  - Characterization of the murine Icam-1 gene.
AB  - Intercellular adhesion molecule-1 (ICAM-1, CD54) is a cell adhesion molecule that
      interacts with the leukocyte beta 2 integrins, LFA-1 and Mac-1. Murine
      inflammatory models are being utilized increasingly to define the role that ICAM
      1 induction plays in the initiation of inflammation. We have isolated murine
      genomic clones that contain the Icam-1 gene including over 2 kb of 5' flanking
      sequence. The gene for murine Icam-1 spans over 13 kb and is composed of seven
      exons and six introns. Each of the extracellular immunoglobulin-like domains of
      ICAM-1 is encoded by a single exon that ends with the first base of the next
      codon. Examination of ICAM-1 expression in vivo shows that mRNA levels of ICAM-1
      are low in all organs except for the lung but increase markedly in multiple
      organs at 3 h after administration of endotoxin. The 5' flanking region of the
      murine gene contains a putative TATA box and potential SP-1, AP-1, and AP-3 sites
      in positions nearly identical to those in the human gene.

PMID- 1362181
TI  - Genetic mapping of a new homeobox gene to mouse chromosome 7.
AB  - A newly identified homeobox gene designated Dbx has been mapped to mouse
      Chromosome (Chr) 7. This gene is expressed in a restricted manner in developing
      mouse brain and spinal cord and has amino acid sequence similarities with members
      of the homeobox gene family such as Drosophila H2.0 and mouse Hlx. Using a
      fragment of the Dbx cDNA as a probe, a PstI restriction fragment length
      polymorphism was used to determine genotypes of 144 progeny from an interspecific
      backcross. Segregation analysis revealed linkage of Dbx with six prepositioned
      reference loci on mouse Chr 7. No recombination was observed between Dbx and Odc
      rs6, indicating that Dbx lies approximately 25 cM distal to the Chr 7 centromere
      in a region that has conserved linkage relationships with regions of human Chrs
      11 and 19.

PMID- 1362182
TI  - The gene for dominant white color in the pig is closely linked to ALB and PDGRFRA
      on chromosome 8.
AB  - White is a widespread coat color among domestic pig breeds and is controlled by
      an autosomal dominant gene I. The segregation of this gene was analyzed in a
      reference pedigree for gene mapping developed by crossing the European wild pig
      and a Large White domestic breed. The gene for dominant white color was shown to
      be closely linked to the genes for albumin (ALB) and platelet-derived growth
      factor receptor alpha (PDGFRA) on chromosome 8. An unexpected phenotype with
      patches of colored and white coat was observed among the F1 and F2 animals. The
      segregation data indicated that the phenotype was controlled by a third allele,
      denoted patch (Ip), most likely transmitted by one of the Large White founder
      animals. It is shown that the ALB, PDGFRA, I linkage group shares homologies with
      parts of mouse chromosome 5, human chromosome 4, and horse linkage group II, all
      of which contain dominant genes for white or white spotting. Candidate genes for
      the dominant white and patch mutations in the pig are proposed on the basis on
      these linkage homologies and the recent molecular definition of the dominant
      white spotting (W) and patch (Ph) mutations in the mouse.

PMID- 1362183
TI  - Enhanced proliferative cellular responses to HIV-1 V3 peptide and gp120 following
      immunization with V3:Ty virus-like particles.
AB  - The induction of CD4+ T-helper (Th) cell responses is likely to be an important
      requirement of vaccine candidates designed to prevent or moderate human
      immunodeficiency virus-1 (HIV-1) infection. We have investigated the ability of
      hybrid Ty virus-like particles carrying the V3 loop region of the HIV-1 IIIB
      envelope gp120 (V3:Ty-VLP) to elicit V3-specific proliferative responses.
      Significant proliferation in response to stimulation in vitro with homologous
      IIIB V3 peptide was observed following immunization of mice with V3:Ty-VLP either
      as an aluminium hydroxide precipitate or without adjuvant. Responses to MN V3
      peptide were also observed in certain mouse haplotypes. To assess the effect of
      presenting the V3 loop in this particulate form, we compared the responses
      induced by V3:Ty-VLP with those obtained with two non-particulate immunogens,
      recombinant gp120 (rgp120) and V3 peptide conjugated to albumin. V3-specific
      responses to V3 peptide in vitro were reproducibly higher following immunization
      with V3:Ty-VLP than with either rgp120 or V3-albumin coagulate (V3-alb). The data
      indicate that immunization with the V3 loop as a hybrid Ty-VLP results in
      enhanced proliferative responses to V3 peptide and recognition of rgp120 in
      vitro. Some cross-reactivity of Th cells for V3 sequences from different isolates
      was also observed.

PMID- 1362186
TI  - Oral contraceptives: an epidemiological perspective.
AB  - Oral contraceptives (OCs) containing a fixed dose of estrogen and progestogen in
      a 21-day regimen initially were approved for unrestricted use in the 1960s in the
      United States. OCs have been used and studied extensively for more than 30 years.
      They have always been seen as providing excellent efficacy. However, estrogens
      were associated with major risks in the use of OCs. In the early 1960s, case
      reports of thromboembolism in women using OCs led to epidemiological studies
      suggesting a correlation between deep vein thrombosis and the estrogen content of
      the pill. Research focused on decreasing the estrogen dose. In the evolution
      process, the combination monophasics of the early 1960s gave way to the
      sequential pill and the "mini pill" of the 1970s. Sex steroids given in the form
      of OCs were shown to alter lipoprotein and carbohydrate metabolism. This,
      together with the increased risk of thromboembolism, led to increased risk of
      cardiovascular disease, e.g., myocardial infarction. Little consideration (in the
      early 1960s) was given to the effects of potent progestogens and their
      interaction with estrogens. Hence, the recent focus of clinical research is the
      development of new and improved progestational agents. These third-generation
      gonane types appear to have little impact on carbohydrate or lipoprotein
      metabolism while maintaining excellent efficacy and cycle control. They should
      reduce the risk of serious side effects. However, to understand how and why these
      agents evolved, tracing the history of OC development is valuable. It might allow
      us to determine the baseline dose where we will begin to lose some of the OCs'
      benefits.

PMID- 1362184
TI  - Subpopulations of guinea-pig T lymphocytes defined by isoforms of the leucocyte
      common antigen.
AB  - This report presents the characterization of three mouse monoclonal antibodies
      (mAb) reactive with the guinea-pig leucocyte common antigen (LCA); CD45 in the
      human nomenclature. One, IH-1, reacted with LCA on all leucocytes. The other two
      were more restricted: IH-2 recognized only the 220,000, 210,000 and 195,000 MW
      isoforms, and IH-4 the 220,000, 210,000 MW isoforms. Both IH-2 and IH-4 reacted
      with all B cells and all Kurloff cells [the putative guinea-pig natural killer
      (NK) cell]. IH-2, but not IH-4, reacted with monocytes and macrophages. Neither
      reacted with neutrophils. Most thymocytes expressed low levels of the IH-2 and IH
      4 epitopes, with those expressing high levels located predominantly within the
      medulla. Most (90%) CD4+ T cells from newborn guinea-pigs expressed high levels
      of the IH-2 and IH-4 epitopes; this percentage decreased with age to 70% in 2
      year-old animals. We have demonstrated that CD4+ T cells which express low levels
      of the IH-2 epitope also express low levels of the IH-4 epitope. CD8+ T cells can
      be divided into two subsets by IH-4 but not IH-2. The reactivities of IH-2 and IH
      4 are remarkably similar to those of human anti-CD45RB and anti-CD45RA antibodies
      respectively. Analogies with man and other species suggest important functional
      differences for subpopulations of guinea-pig T lymphocytes defined by anti-CD45R
      antibodies.

PMID- 1362187
TI  - The underrated benefits of oral contraception: consequences of pregnancy and
      induced abortion in teenagers.
AB  - If complications occur within a pregnancy planned and brought to term, they often
      can be dealt with and accepted. They are even more traumatic when they occur in
      an unwanted pregnancy that could have been prevented through contraception.
      Teenagers, because of their physical and psychological immaturity and also
      because of their social environment, seem to suffer with undue frequency from the
      complications of induced abortion. Its result, for the teenager, is a handicapped
      future in comparison to other women. Hence, access to contraception is important
      for all women, and especially for teenagers, in order to avoid such prejudicial
      situations. It is important, then, to prescribe oral contraception for its
      efficacy and its short- and long-term innocuousness. Because of her immaturity,
      the pregnant teenager is at risk: of spontaneous abortion, pre-eclampsia, anemia,
      hemorrhage, and prematurity. She is also at risk because of the social
      difficulties she will be facing. This is particularly true in families from
      developing countries. From birth, the child is also at risk: of low birth weight
      for the term, mortality in the first year of life, and all risks linked to
      abandonment, or education by a third party. In a proportion of 13 to 30% in
      western countries and in a proportion of 3% in East Asia or in Northwest Africa
      (Maghreb), induced abortions are a reflection of the following: early sexual
      activity without contraception even if fertility is still low in very young
      teenagers, absence of social protection or social independence, refusal of forced
      marriage, and presence or absence of liberal legislation.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1362185
TI  - Studies on the susceptibility to NK-mediated lysis and the simultaneous
      expression of various surface molecules in anthracyclin-treated K562 cells and in
      four K562 cell clones.
AB  - Target molecules for NK cells are unknown. Numerous studies have proposed
      putative target molecules, but have examined their role in the modulation of
      sensitivity to NK-mediated lysis one independently of each other. We examined the
      simultaneous expression of various surface molecules and the susceptibility of
      K562 cells to NK attack. We have previously shown that adriamycin (40 nM) and
      aclacinomycin (15 nM) can induce, in vitro, an increase of glycophorin A (GPA) on
      K562 cells, a modulation of transferrin receptor (TfR) and CD15 antigen
      expression and a significant resistance of cells to NK-mediated lysis. In the
      present work, Fc gamma receptor II (CD32) expression at the K562 cell membrane
      was clearly decreased after aclacinomycin-treatment but was unaltered by
      adriamycin-treatment. Four K562 cell clones were studied. Two clones (F and G)
      expressed a higher level of CD32 at the membrane (62% and 70% of erythrocyte
      antibody (EA) rosettes respectively) and two clones (9 and 19) expressed lower a
      level (18% and 7% EA rosettes respectively) than the original population (43%).
      The sensitivity to lysis by NK cells was increased in clones F, G and 9 but
      decreased in clone 19 (without alteration in the binding capacity). Relationships
      between the sensitivity to NK attack and the levels of simultaneous expression of
      CD32, TfR, CD15, glycophorin A (GPA) and MHC class I monomorphic antigens were
      studied. In addition, the presence at the membrane of some cellular adhesion
      molecules (CD54, CD58, CD29, CD18, CD56) was examined in anthracyclin-treated
      cells and in the four clones. The difference in the sensitivity of target cells
      to NK attack is not strictly related to variation of one or other of these
      molecules. Our previous and present data suggest that the resistance of K562
      cells to NK cells may correlate with the level of erythroid maturation at the
      cell membrane, involving simultaneous variations in expression of several
      molecules such as a decrease of TfR, CD15 and CD32 and an increase of GPA.

PMID- 1362188
TI  - The androgenicity of oral contraceptives: the young patient's concerns.
AB  - Sexual activity is quite common among women aged 14 to 20 in developed countries,
      averaging perhaps 10% at age 15 to about 70% at 19. Thus, the need for
      contraception may begin quite early in life and will continue for as long as 30
      years. One of the best candidates for long-term contraception for young sexually
      active females is the oral contraceptive (OC), which provides health benefits
      besides contraception. Long-term benefits include lowered rates of ovarian and
      endometrial cancer, as well as of benign breast disease and ovarian cysts.
      Another benefit is protection against upper-tract sequelae of sexually
      transmitted diseases. Short-term benefits are correction of menstrual
      irregularity, reduction in menstrual flow, and diminished premenstrual syndrome
      and dysmenorrhea. Recent OC formulations contain only one-third the estrogenic
      potency of older OCs and therefore are associated with dramatic decreases in what
      were always the major side effects of OCs: heart attack, stroke, and pulmonary
      embolism. Other side effects of OCs have been most closely associated with the
      progestogenic component, and are related to the androgenic effects of progestins,
      particularly some synthetic progestins. However, some new synthetic progestins
      have been found to have minimal androgen receptor activity in preclinical testing
      and to cause minimal or no androgen-related side effects in clinical trials. One
      of these new progestins having a favorable androgenic profile is norgestimate.
      Its efficacy and safety in combination with low doses of ethinyl estradiol have
      been documented in the European and the American literature.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1362189
TI  - Long-term profile of a new progestin.
AB  - Major complications attributable to oral contraceptives (OCs) may occur in the
      circulatory system. The inherent risk factors, such as race and family history,
      are unchangeable. Others may be altered by patient counseling and subsequent
      adjustment of certain behaviors. Hypercoagulability is estrogen dose related.
      Older, high-dose-estrogen OC users were at 40% increased risk of mortality from
      thromboembolic phenomena. Reduction in estrogen content has unmasked the
      androgenic effects of some synthetic progestogens. These effects may include
      progression of atherogenesis, effected through changes in cholesterol and
      lipoproteins; reduction in sex hormone binding globulin (SHBG), which enhances
      the androgenic effect; and changes in carbohydrate metabolism. This review of
      clinical findings is based on four studies; three had prospective cohort designs,
      and one was a prospective randomized comparison of a norgestimate-containing OC
      with a norgestrel-containing one. Numbers of subjects ranged from 20 to 59,701;
      the largest evaluated 343,348 cycles of treatment. Study intervals were from 4 to
      24 months. The findings reported here are from the individual studies. 1. The
      normal value for cholesterol is less than 200 mg/dL. Of 2,197 women who met this
      cut-off point, 95% remained below it after 6 months of treatment. Of 756 who
      initially exceeded this value, 25% were below after 6 months and 75% remained
      above it. All studies to date have demonstrated that norgestimate produces
      consistent and significant elevations in high-density lipoprotein levels and
      variable change in low-density lipoproteins. A similar effect was noted on serum
      triglyceride values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362190
TI  - [Classification of findings and staging of endocrine diseases].

PMID- 1362191
TI  - 1st International Workshop on CD15. Dusseldorf, 14-15 December 1991.

PMID- 1362193
TI  - Le(X) and related structures as adhesion molecules.
AB  - Le(x) (alpha 1-->3 fucosylated type 2 chain) functions as an adhesion molecule
      capable of Ca(2+)-mediated homotypic binding. Cells with high surface expression
      of Le(x) therefore exhibit strong self-aggregation (based on Le(x)-Le(x)
      interaction) in the presence of Ca2+. In this review, I have summarized several
      lines of supporting data for this concept, and the role of Le(x)-Le(x)
      interaction in the process of embryo compaction and autoaggregation of F9
      teratocarcinoma cells. In general, cell adhesion events based on Le(x)-Le(x)
      interaction may be followed and reinforced by integrin- or Ig receptor-based
      adhesion systems. SLe(x), the 2-->3 sialosyl derivative of Le(x), and its
      positional isomer SLe(a), have been identified as the target molecules for
      selectin-dependent cell adhesion. Adhesion of leukocytes or tumour cells to ECs
      or platelets, which express E-selectin and P-selectin respectively, is initiated
      by this process. The target epitopes SLe(x) and SLe(a) are presented mainly on
      transmembrane glycoproteins having many clusters of O-linked carbohydrate chains.
      Therefore, inhibition of O-glycosylation may be effective for blocking selectin
      mediated cell adhesion. The abundant presence of Le(x) epitope in the central
      nervous system, and the physiological changes of Le(x) expression as described in
      this monograph, reflect the adhesive properties of this molecule and its
      sialyosylated and/or fucosylated derivatives.

PMID- 1362194
TI  - Expression of CD15 (FAL) on myeloid cells and chromosomal localization of the
      gene.
AB  - Different CD15 murine monoclonal antibodies were studied. These antibodies
      appeared to react specifically with the human myeloid-lineage-derived cell types
      in both peripheral blood and bone marrow. The antigens recognized by these
      antibodies were immunoprecipitated from lysates of 125I-labelled neutrophilic
      PMNs of healthy donors and subsequently analysed by electrophoresis on SDS
      polyacrylamide gel and autoradiography. All antibodies precipitated the same
      membrane polypeptides from the membrane-iodinated PMN lysates: 105 and 150-kDa as
      most prominent, together with 260-, 230-, 67- and 52-kDa polypeptides. Absorption
      studies were performed with synthesized carbohydrate molecules. Antibody B4.3
      appears to be directed against 3-alpha-fucosyl-N-acetyl-lactosamine (FAL).
      Competition experiments with 125I-labelled B4.3 demonstrated complete inhibition
      of binding by B4.3 and three other CD15 antibodies (VIM D5, UJ308, MI/N1), and
      partial inhibition by three additional antibodies (FMC10, FMC12, FMC13),
      indicating binding to the same antigenic structure. None of the antibodies
      reacted with monocytes using the immunofluorescence technique, but after
      neuraminidase digestion of these cells, positive reactions were obtained with all
      antibodies. Immunoprecipitation with lysates of both native and neuraminidase
      digested monocytes showed no polypeptide bands. Monocytic differentiation of the
      myeloid cell line HL60 by 12-O-tetradecanoylphorbol-13-acetate (TPA) was
      accompanied by a decrease in reactivity with the antibodies, which could be
      reversed by neuraminidase digestion. This indicates that 3-alpha-fucosyl-N-acetyl
      lactosamine is masked for the detection with antibodies upon monocytic
      differentiation by sialylation. Human x mouse myeloid cell hybrids were obtained
      after fusion of human myeloid cells and the HPRT-deficient murine myeloid cell
      line WEHI-TG.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362192
TI  - Occurrence and specificities of alpha 3-fucosyltransferases.
AB  - The Le(x) (CD15) carbohydrate antigen and sialylated and oligomeric derivatives
      thereof have been implicated in cell adhesion processes. Expression of these
      antigens is developmentally regulated and (re)occurrence of several members of
      this group has been reported in malignant transformation of cells. Studies on the
      enzymology and genetics of alpha 3-fucosyltransferases, glycosyltransferases that
      play a key role in the biosynthesis of these antigens, would yield insight in the
      regulation of expression of these carbohydrate structures. In this paper the
      existing literature on these enzymes is reviewed and placed in the context of
      cell adhesion and malignancy.

PMID- 1362196
TI  - Retinoic acid increases CD15 expression in immortalized rat astrocytes.
AB  - We have studied the expression of the CD15 (3-fucosyl-N-acetyl-lactosamine)
      epitope on immortalized astroglial cells derived from embryonic (E 19/20) rat
      brain. Immortalization was achieved by pulse-treatment of primary culture with 5
      azacytidine. Seventy-three permanent cell lines were established by repeated cell
      cloning. Clones expressing GFAP, A2B5, and vimentin were regarded as immature
      astrocytes. One of these clones expressing CD15 was selected for manipulation
      studies. Monoclonal antibody was used for immunocytochemical detection of CD15
      epitope and in immunoblot analysis. CD15 expression was visible in about 20% of
      the cells and was associated with a special morphological appearance. In the
      presence of retinoic acid the proportion of CD15-positive cells increased in a
      time-dependent manner, reaching about 90% within four days. Again, this
      expression was associated with the formation of distinct morphological features,
      including immunoreactive perinuclear granula, tips of processes and contact
      sites. After treatment with neuraminidase, all cells showed CD15-positive
      immunoreaction, revealing the presence of the epitope masked by sialylation.
      Immunoblot patterns of glycoproteins from trypsinized and mechanically detached
      cell preparations suggest that proteins, carrying sialylated CD15, might
      represent intracellular precursors of extracellularly active molecules.

PMID- 1362198
TI  - Transient expression of stage-specific embryonic antigen-1 (CD15) in the
      developing dorsal rat spinal cord.
AB  - The localization of CD15 (synonyms: stage-specific embryonic antigen-1 (SSEA-1),
      3(alpha)-fucosyl-N-acetyl-lactosamine or FAL), which is implicated in neuronal
      differentiation, in the developing dorsal rat spinal cord was studied by
      immunocytochemistry. A embryonal day 9 (E9), SSEA-1 was detected in the neural
      ectoderm and, at E11, in cells near the ventricle of the matrix layer. This
      localization indicated that SSEA-1 is present in proliferating premigratory cells
      of the rat spinal cord. Between E12 and E16, cells of the alar plate expressed
      SSEA-1. Expression of the antigen was restricted to neuroblasts that will form
      the dorsal horn. SSEA-1, therefore, can be used at this stage as a marker for a
      subdivision of the matrix layer. At E14, the dorsal root entrance zone showed
      SSEA-1. This indicated that SSEA-1 is associated with ingrowing primary
      afferents. From E16 on, SSEA-1 was present in the dorsal raphe, which suggested a
      function for SSEA-1 in the guidance of developing fibres. After E17, the antigen
      was also found within the dorsal mantle layer. SSEA-1 was first present in
      Rexed's laminae II, IV and V. Later on in development the antigen was detected
      only in Rexed's laminae II (substantia gelatinosa). These distribution patterns
      indicated that SSEA-1 is present on migratory and/or postmigratory cells. In
      addition, SSEA-1 is associated with small-diameter dorsal root fibres, the C
      fibres and A(sigma) fibres, that terminate within the substantia gelatinosa.
      After birth, SSEA-1 was present throughout the dorsal horn, probably as a result
      of the myelination of the fibres.

PMID- 1362197
TI  - The expression of CD15 in dissociated cultured rat dorsal root ganglion cells.
AB  - This study describes the presence of CD15 in dorsal root ganglia neurons in five
      experimental conditions: chemically defined medium and the same medium with added
      nerve growth factor, retinoic acid or antibodies against insulin or tyrosine
      phosphate. Positive astrocyte controls were used to differentiate the monoclonal
      antibodies that did not react with CD15. Those monoclonal antibodies which
      detected CD15 in this positive control were also used to study CD15 positivity in
      dorsal root ganglion cells. This study shows: (i) masking of the CD15 antibody,
      which influences the detection capacity of the monoclonal antibodies used; (ii)
      that CD15 discerns two subpopulations of DRG neurons: a CD15-positive and a CD15
      negative population; (iii) that CD15 expression is not involved in the outgrowth
      of protrusions or the wrapping by non-neuronal cells of DRG neurons.

PMID- 1362195
TI  - The role of CD15-(Le(X))-related carbohydrates in neutrophil adhesion.

PMID- 1362200
TI  - Requirements for lysis of activated T cells by class-II-restricted cytolytic T
      lymphocytes.
AB  - In the present study, we explored the specific requirements for lysis of human
      activated T cells by CD4+ CTLs. This was achieved by using human CD4+ T cell
      lines or clones specific for a peptidic fragment of influenza virus as both CTL
      effectors and target T cells (TTCs). Our results further establish that human
      activated T cells expressing HLA-DR molecules can present Ag to and be lysed by
      CD4+ HLA-DR restricted CTLs. This killing is Ag specific and HLA-DR restricted.
      It can be observed whether TTCs are heterologous or autologous, CD4+ or CD8+.
      However, we find that in our model: (a) TTCs are able to present artificially
      processed peptidic fragments of Ag, but not the corresponding natural Ag in the
      context of class II determinants, even if they can process whole virus in the
      context of class I determinants; (b) TTCs must express high density of HLA-DR
      molecules on their membrane; (c) preincubation of TTCs with high concentrations
      of peptide is required; and (d) interestingly enough, addition of free peptide at
      similar concentration during the cytolytic assay to replace TTC preincubation
      inhibits TTC lysis by at least two different mechanisms, i.e., cold-target
      inhibition in which CTLs serve as their own cold targets and inhibition at the
      effector cell level. From these results, one can conclude that stringent
      conditions are required for lysis of activated T cells by class-II-restricted
      CTLs.

PMID- 1362199
TI  - Expression of CD15 in tumours of the nervous system.
AB  - The expression of the CD15 epitope was investigated by immunohistochemistry,
      western blotting and immuno-thin-layer chromatography on a large series of human
      nervous system tumours and ethylnitrosourea-induced rat gliomas. Our results show
      that CD15 is expressed as a glycoprotein- or glycolipid-associated epitope in
      normal human and rat brain. In contrast, immunoreactivity for CD15 was absent in
      tumour cells of experimental rat gliomas. In human tumours we found a more
      complex expression pattern. While intra- and perivascular granulocytes as well as
      macrophages in necrotic areas of anaplastic tumours were always strongly CD15
      positive, immunoreactive tumour cells were detectable only in a fraction of low
      grade gliomas. Anaplastic gliomas and glioblastomas consistently did not express
      the epitope on their tumour cells. In addition to individual low-grade gliomas,
      we found CD15-positive cases among metastatic carcinomas, craniopharyngeomas,
      meningiomas, germinomas and malignant melanomas. Our results suggest that
      immunohistochemistry for CD15 is potentially useful in diagnostic neuropathology
      as a marker for granulocytes in paraffin sections, as a supplementary tool for
      the histopathological grading of gliomas, and as an aid for differentiation
      between anaplastic glioma cells and non-neoplastic glia. Furthermore, it can be
      speculated that the lack of CD15 expression on anaplastic glioma cells may
      potentially be responsible for some of their characteristics--such as altered
      cellular interaction and loss of contact inhibition.

PMID- 1362201
TI  - Measurement of glutamate, aspartate and glycine and its potential precursors in
      human brain using high-performance liquid chromatography by pre-column
      derivatization with dimethylaminoazobenzene [correction of
      diethylaminoazobenzene] sulphonyl chloride.
AB  - This paper describes a high-performance liquid chromatographic technique, with
      dimethylaminoazobenzene sulphonyl chloride derivatization, for the measurement of
      glutamate, aspartate and glycine and its potential precursors in human brain
      tissue. The derivatization procedure is simple, sensitive and highly
      reproducible. The derivatized amino acids are stable and can be analysed by
      reversed-phase chromatography with visible detection at an absorption wavelength
      of 436 nm. A preliminary application to the determination of the concentrations
      of several amino acids in several regions of the human brain is described.

PMID- 1362202
TI  - Dipeptidyl peptidase IV as a differentiation marker of the human endometrial
      glandular cells.
AB  - To investigate the involvement of membrane-bound peptidases in the human
      endometrial function, we examined the expression of dipeptidyl peptidase (DPP) IV
      and its enzyme activity. Immunohistological studies revealed that DPP IV was
      detected on human endometrial glandular cells and endometrial surface epithelium,
      but not on endometrial stromal cells or decidual cells in the first trimester of
      pregnancy. DPP IV expression on glandular cells and surface epithelium was weak
      in the proliferative phase, began to increase gradually in the early secretory
      phase, and was strong in mid-to late secretory phase and in the first trimester
      of pregnancy. DPP IV enzyme activity was detected histochemically in glandular
      cells and surface epithelium in the mid-secretory phase, and became stronger in
      the late secretory phase, but was rarely detected in the proliferative phase and
      early secretory phase. During the first trimester of pregnancy DPP IV enzyme
      activity in glandular cells and surface epithelium was slightly weaker than in
      the late secretory phase. Endometrial stromal cells and decidual cells, however,
      had no detectable DPP IV enzyme activity at any time throughout the menstrual
      cycle or during the first trimester of pregnancy. These findings indicate that
      DPP IV is a differentiation marker for glandular cells and surface epithelium and
      that active DPP IV is present in both areas during the peri-implantation period
      and thereafter.

PMID- 1362203
TI  - Preimplantation diagnosis of a human beta-globin transgene in biopsied
      trophectoderm cells and blastomeres of the mouse embryo.
AB  - The preimplantation diagnosis of a HbSA-globin transgene in biopsied
      trophectoderm cells and blastomeres in embryos using a transgenic mouse model for
      the trait of human sickle-cell anaemia has been undertaken. A sensitive procedure
      was developed for the amplification of the human beta-globin gene sequence
      flanking the sickle mutation. Polymerase chain reaction (PCR) assays were
      undertaken on one to five biopsied trophectoderm cells and isolated blastomeres
      of the preimplantation mouse embryo. After biopsy the blastocysts were cultured
      whilst the cells were analysed for the presence of the transgene, and a high
      proportion (82-91%) were viable as assessed by the presence of a blastocoele
      cavity within a 5-h period. The majority of the biopsied cultured blastocysts
      were frozen and used to confirm the diagnosis; 90 biopsied cultured blastocysts
      were transferred to pseudopregnant recipients and 34% established pregnancy.
      Material from day 13.5 post-coitum fetuses was also used to confirm the original
      diagnosis. The time (4-5 h) required to carry out the analysis obviates a need
      for extended culture or cryopreservation of the biopsied embryo. In individual
      experiments under optimal conditions, the presence of the transgene in biopsied
      cells was detected with 100% accuracy, and the PCR analysis was sensitive at the
      1-cell level. The overall success rate of diagnosis and confirmation of the
      presence or absence of the human beta-globin sequence in the biopsied embryo was
      70%. Over the entire experimental period (14 months) DNA contamination from a
      variety of sources did occasionally occur; the methods used to overcome this
      problem are discussed.

PMID- 1362204
TI  - Expression of aminopeptidase N and neutral endopeptidase on the endometrial
      stromal cells in endometriosis and adenomyosis.
AB  - Indirect immunofluorescence staining revealed that endometrial stromal cells
      (ESC) in the ectopic endometrium of patients with endometriosis or adenomyosis
      expressed aminopeptidase N/cluster of differentiation (CD) 13 antigen and neutral
      endopeptidase/CD10 antigen, both of which are expressed on ESC in the normal
      endometrium throughout the menstrual cycle. Thus, ESC in the ectopic endometrium
      resembled ESC in the normal endometrium not only morphologically but also
      antigenically. Both peptidase antigens may be useful markers for the histological
      diagnosis of endometriosis and adenomyosis.

PMID- 1362205
TI  - Placebo-controlled, double-blind study of the effects of proglumide in the
      treatment of schizophrenia.
AB  - A double-blind, placebo-controlled, randomized study was performed to determine
      whether proglumide added to ongoing neuroleptic medication was efficacious in the
      treatment of 32 patients with persistent positive and negative schizophrenic
      symptoms. Patients treated with both proglumide and placebo showed a significant
      improvement over the 8 weeks of the study, but no significant difference between
      the patients taking proglumide and those taking placebo could be demonstrated. In
      addition, proglumide had no effect on plasma homovanillic acid concentrations or
      neuroleptic drug activity. The results suggest that, at least for the dose of
      proglumide used in this study (15 mg/day), the addition of this particular
      cholecystokinin antagonist does not potentiate the antipsychotic efficacy of
      neuroleptic medication in patients with persistent schizophrenic symptoms.

PMID- 1362206
TI  - Kinetics, brain uptake, and receptor binding of tandospirone and its metabolite 1
      (2-pyrimidinyl)-piperazine.
AB  - Tandospirone is an azaspirodecanedione derivative under investigation as an
      antidepressant. Metabolism of tandospirone in humans and rodents leads to 1-(2
      pyrimidinyl)-piperazine (1-PP), presumed to have pharmacologic activity. To
      determine the relative contributions of tandospirone and 1-PP after tandospirone
      administration, we evaluated open-field activity, pharmacokinetics, and receptor
      binding of tandospirone and 1-PP in a mouse model. Tandospirone significantly
      reduced open-field activity during 30 minutes at doses of 1-20 mg/kg. 1-PP had no
      significant effect on activity except for a trend toward reduction at 20 mg/kg.
      At 30 minutes after administration, plasma and cortex concentrations of
      tandospirone and 1-PP increased in proportion to dose. Plasma protein binding
      (free fraction) for tandospirone was 30.4%, and for 1-PP, 87.5%. Receptor binding
      studies indicated that tandospirone bound with high affinity to serotonin1A
      sites, and with low affinity to serotonin2, alpha 1, alpha 2, and benzodiazepine
      sites. 1-PP bound with high affinity to alpha 2 sites and with low affinity to
      the other sites evaluated. A "receptor occupancy index" of tandospirone cortex
      concentrations divided by receptor affinity suggests that after acute
      administration of tandospirone, effects are likely to be due to the parent
      compound rather than to the metabolite. Similar conclusions are likely to be
      correct for other azaspirodecanediones, including buspirone.

PMID- 1362207
TI  - Topographic organization of cardiovascular responses to electrical and glutamate
      microstimulation of the parabrachial nucleus in the rat.
AB  - We examined the functional organization of the parabrachial complex (PB) by
      mapping the cardiovascular and respiratory responses to PB microstimulation in
      anesthetized rats. The PB was explored with 100 microns resolution, at threshold
      doses of electrical current (5 microA) and glutamate (10-500 pmols), and the
      locations of stimulation sites were identified by small iontophoretic or pressure
      injections of biocytin or Phaseolus vulgaris leucoagglutinin. Threshold doses of
      either L-glutamate or electrical current pulses caused pressor-tachycardic
      responses that mapped to the outer edge of the external lateral subnucleus while
      depressor bradycardic responses were elicited from stimuli near the dorsal
      lateral subnucleus. Pressor responses persisted in paralyzed, ventilated animals
      and were thus not dependent upon concomitant respiratory changes. Cardiac
      arrhythmias sometimes occurred during large pressor responses and during
      augmented breaths that occurred during or following PB stimulation. These
      observations indicate that the PB contains at least two distinct neuronal systems
      that are potently and opposingly involved in cardiovascular control. The
      locations of the sites giving the most potent responses implicate specific
      ascending and descending pathways as substrates for the cardiovascular responses.

PMID- 1362208
TI  - Postnatal development of tyrosine hydroxylase immunoreactive amacrine cells in
      the rabbit retina: II. Quantitative analysis.
AB  - Tyrosine hydroxylase (TH)-immunoreactive (IR) amacrine cells of the rabbit retina
      mature during the first four postnatal weeks, and their cellular development is
      described in the preceding paper (Casini, G., and N.C. Brecha, J. Comp. Neurol.
      326:283-301, 1992). The present investigation is a quantitative analysis of the
      postnatal development of the TH-IR amacrine cell population. TH-IR amacrine cells
      gradually increase in size from birth (soma area of 44.7 +/- 12.4 microns2, mean
      +/- standard deviation) to adulthood (144.2 +/- 28.0 microns2). Cell density
      slightly increases from postnatal day (PND) 0 (41.9 +/- 9.5 cells/mm2) to PND 6
      (47.2 +/- 7.2 cells/mm2), then markedly decreases from PND 6 to adulthood (17.8
      +/- 5.3 cells/mm2) as a consequence of retinal growth. TH-IR cell number almost
      doubles from PND 0 (about 4,100 cells/retina) to adulthood (about 7,850
      cells/retina). The increase in the total number of TH-IR amacrine cells can be
      explained by the generation of new TH-IR cells in the inner nuclear layer, a
      delay in the expression of the TH phenotype after neurogenesis by cells committed
      to be dopaminergic, or the acquisition of this dopaminergic phenotype by
      uncommitted cells. The development of the TH-IR amacrine cell mosaic was assessed
      by an evaluation of the distribution of nearest neighbor distances of TH-IR
      cells. There is a poor correlation between this distribution and a theoretical
      nonrandom distribution before PND 12. After this age, the nearest neighbor
      distance distribution shifts towards a nonrandom distribution, and is similar to
      that of the TH-IR amacrine cell population in the adult retina. The establishment
      of the TH-IR amacrine cell population mosaic is likely to be achieved through
      different interacting events, including intrinsic (e.g., genetic) factors,
      environmental influences, and nonuniform retinal growth. Overall, the population
      parameters analyzed in the present study approach adult values about the time of
      eye opening (PND 12) and they reach adult values by PND 26.

PMID- 1362210
TI  - Stress proteins and cross-protection by heat shock and salt stress in Bacillus
      subtilis.
AB  - Bacillus subtilis induced a set of general stress proteins in response to a salt
      or heat stress. Cells subjected to a mild heat stress showed a protective
      response which enabled them to survive otherwise lethal temperatures (e.g. 52
      degrees C). In a similar way bacteria were enabled to survive toxic
      concentrations of NaCl by pretreatment with lower salt concentrations. A mild
      heat shock induced a cross-protection against lethal salt stress. The
      pretreatment of cells with low salt, however, was less effective in the induction
      of thermotolerance than a preceding mild heat stress. Three stress proteins were
      identified on the basis of their N-terminal amino acid sequences as homologues of
      GroEL, DnaK and ClpP of Escherichia coli. The role of general and specific stress
      proteins in the induction of thermotolerance/salt tolerance and cross-protection
      is discussed.

PMID- 1362209
TI  - Verrucous lesions secondary to DNA viruses in patients infected with the human
      immunodeficiency virus in association with increased factor XIIIa-positive dermal
      dendritic cells. The Military Medical Consortium of Applied Retroviral Research
      Washington, D.C.
AB  - BACKGROUND: Hyperkeratotic lesions caused by varicella-zoster, herpes simplex, or
      cytomegalovirus occur in patients infected with human immunodeficiency virus type
      1 (HIV-1). We have also observed this type of lesion with molluscum contagiosum.
      OBJECTIVES: These cases were studied to determine whether there are any
      pathologic changes unique to these lesions. METHODS: The cases were studied by
      routine microscopic examination and immunohistochemistry. RESULTS: Each case
      showed changes diagnostic of the viral infection, which was confirmed by
      immunohistochemical stains for herpes simplex and cytomegalovirus. In the dermis
      there were fewer inflammatory cells than expected, but there was an increase in
      factor XIIIa-positive dendritic cells. CONCLUSION: Varicella-zoster, herpes
      simplex virus, cytomegalovirus, and molluscum contagiosum can cause verrucous
      lesions in HIV-1-infected patients. These lesions may be related to an increase
      in factor XIIIa-positive dendritic cells.

PMID- 1362211
TI  - Computer-assisted pattern recognition model for the identification of slowly
      growing mycobacteria including Mycobacterium tuberculosis.
AB  - We present a computerized pattern recognition model used to speciate mycobacteria
      based on their restriction fragment length polymorphism (RFLP) banding patterns.
      DNA fragment migration distances were normalized to minimize lane-to-lane
      variability of band location both within and among gels through the inclusion of
      two internal size standards in each sample. The computer model used a library of
      normalized RFLP patterns derived from samples of known origin to create a
      probability matrix which was then used to classify the RFLP patterns from samples
      of unknown origin. The probability matrix contained the proportion of bands that
      fell within defined migration distance windows for each species in the library of
      reference samples. These proportions were then used to compute the likelihood
      that the banding pattern of an unknown sample corresponded to that of each
      species represented in the probability matrix. As a test of this process, we
      developed an automated, computer-assisted model for the identification of
      Mycobacterium species based on their normalized RFLP banding patterns. The
      probability matrix contained values for the M. tuberculosis complex, M. avium, M.
      intracellulare, M. kansasii and M. gordonae species. Thirty-nine independent
      strains of known origin, not included in the probability matrix, were used to
      test the accuracy of the method in classifying unknowns: 37 of 39 (94.9%) were
      classified correctly. An additional set of 16 strains of known origin
      representing species not included in the model were tested to gauge the
      robustness of the probability matrix. Every sample was correctly identified as an
      outlier, i.e. a member of a species not included in the original matrix.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1362213
TI  - Iron and akathisia.

PMID- 1362212
TI  - The effect of withdrawal of dopaminergic medication on simple and choice reaction
      time and the use of advance information in Parkinson's disease.
AB  - Eight patients with Parkinson's disease performed simple reaction time (SRT),
      uncued, partially and fully cued four choice (CRT) tasks. They were tested on two
      occasions; on their normal dose of dopaminergic medication and following
      withdrawal of such medication for an average of 14.4 hours. Disability as rated
      on the Webster scale was greater in the drug reduced state. Although RTs were
      generally slower when tested in the drug reduced state than when on medication,
      few differences emerged. Withdrawal of dopaminergic medication had no effect on
      unwarned SRT and unwarned and uncued CRT performance. Both on and off medication,
      the patients benefited from a warning signal presented before the imperative
      stimulus. In both medication states, the speeding up of RT was greatest with a
      warning signal presented 200 ms before S2. When the imperative stimulus was
      unwarned, the temporal predictability of its occurrence speeded RT more when on
      medication than when off. Advance movement parameter information was used by
      patients to pre-programme responses both on and off medication. In both
      medication states, the fully cued CRT was the same as SRT only with the 3200 ms
      S1-S2 interval. Medication state had no effect on movement time or the number of
      errors. It is suggested that slowness in motor readiness and motor programming
      may not be specific to striatal dopamine deficiency but rather a nonspecific
      concomitant of brain damage.

PMID- 1362214
TI  - K-dependent inhibition in the dentate-CA3 network of guinea pig hippocampal
      slices.
AB  - 1. The occurrence of potassium-dependent inhibitory postsynaptic potentials (K
      IPSPs) in relation to burst discharges induced by 4-aminopyridine (4-AP; 30
      microM) was studied in CA3, granule and hilar neurons in guinea pig hippocampal
      slices with the use of paired extra- and/or intracellular recording. 2. Slow
      small (2-5 mV) and large (up to 30 mV) K-IPSPs were observed in CA3, granule and
      in some hilar neurons during 4-AP applications in the presence of blockers for
      fast synaptic transmission, picrotoxin (50 microM), and 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX; 5-10 microM). Amplitudes of K-IPSPs were
      linearly related to voltage, and they reversed in sign close to -100 mV, as
      expected for synaptic potentials generated by an increase in K-conductance. 3. In
      CA3 neurons, 4-AP applied in the presence of picrotoxin elicited burst discharges
      and K-IPSPs. CNQX blocked the burst discharge activity and increased the
      amplitude of K-IPSPs. 4. In granule cells, 4-AP applied in the presence of
      picrotoxin elicited K-IPSPs and only inconsistently small excitatory postsynaptic
      potentials (EPSPs). The EPSPs were blocked by CNQX, but CNQX application did not
      affect the K-IPSPs. However, in granule cells it could be observed that blockade
      of Cl-inhibition by picrotoxin in the presence of CNQX increased the amplitude of
      K-IPSPs. 5. In hilar neurons, 4-AP applied in the presence of picrotoxin elicited
      mainly burst discharges. CNQX blocked the burst discharges only in a few cells.
      In most hilar neurons K-IPSPs were observed at the beginning of the 4-AP effect,
      but subsequently K-IPSPs were replaced by burst discharges. 6. To determine the
      type of cells that burst in picrotoxin and 4-AP, neurons were stained
      intracellularly with horseradish peroxidase. Neurons stained in the granule cell
      layer did not burst and were morphologically identified as granule cells. Neurons
      stained in the hilar region burst and were nonpyramidal, nongranule cells.
      Bursting cells stained in the CA3 area were all pyramidal cells. 7. The hilar
      neurons varied considerably in size and dendritic organization. They could be
      classified as aspiny and spiny cells, the latter including mossy cells. 8. We
      conclude that K-dependent inhibition may explain the long-lasting IPSPs observed
      in in vivo recordings from hippocampal cells. In a hippocampal lamella, burst
      discharge activity of hilar neurons including presumed excitatory mossy cells is
      associated with inhibition of granule cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1362215
TI  - Role of sympathetic innervation in the feline continence process under natural
      filling conditions.
AB  - 1. The effect of the sympathetic innervation on the bladder detrusor muscle was
      assessed in pentobarbitone-anesthetized cats by measuring the changes in bladder
      wall tension that occurred during sympathetic ganglion blockade after filling the
      bladder at a natural rate. 2. At a point 60% of the way through the continence
      process, systemic sympathetic blockade was produced by intravenous trimethaphan,
      and selective blockade of postganglionic hypogastric nerve activity was produced
      by application of trimethaphan to the exposed inferior mesenteric ganglia. The
      level of blockade was monitored with an in-continuity hypogastric nerve
      recording. 3. During both systemic and selective ganglion blockade, there was an
      increase in baseline transmural bladder pressure and a decrease in the amplitude
      of nonmicturating contractions. 4. Although there was no change in the mean level
      of transmural bladder pressure during either systemic or selective blockade,
      there was a significant increase in the mean level of bladder wall
      mechanoreceptor discharge, suggesting that before the blockade sympathoinhibitory
      effects were greater than sympathoexcitatory effects. 5. Measurement of bladder
      wall mechanoreceptor discharge before and during ganglion blockade revealed a net
      sympathoinhibitory influence on the level of bladder wall tension under natural
      filling conditions. These results confirm that the detrusor muscle of the feline
      bladder is under both sympathoinhibitory and sympathoexcitatory influences for a
      significant portion of the continence process.

PMID- 1362216
TI  - Differences of L-myc polymorphic patterns of neuroblastoma in patients under 1
      year versus older ages: a preliminary report.
AB  - The age of the patient at the onset of symptoms or at diagnosis is generally
      accepted as one of the most important prognostic factors of neuroblastomas (NBs).
      Children less than 1 year of age have a better survival rate than older patients,
      but the reason for this is unknown. Forty-eight unselected NB patients were
      divided into two groups: less than 1 year (younger NB patient) and over 1 year
      (older NB patient) of age at diagnosis. Two of 12 younger NB patients and 18 of
      36 older NB patients had N-myc amplification in their tumors. To elucidate
      further the possible genetic difference between younger and older NB patients,
      studies of restriction fragment length polymorphism (RFLP) of the L-myc gene was
      carried out in these two groups. The L-myc locus showed 2-allele polymorphism,
      allele L(10 kb) and S (6.6 kb), after digestion with EcoRI. Patients homozygous
      for L-band have been reported as individuals having less metastatic potential in
      some cancers. The allele frequencies of L and S in neuroblastomas of younger NB
      patients were 0.50 and 0.50, while those of older NB patients were 0.35 and 0.65,
      respectively. Although we did not determine L-myc RFLP in normal tissue of
      individual patients, we expect that the distribution of allele L and S is partly
      affected by possible allelic loss involving the L-myc region. However, the L-myc
      RFLP patterns in younger NB patients were the same as those of normal individuals
      and significantly differed from those of older NB patients.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1362217
TI  - Methodologies in Evaluation of Periodontal Therapy. Symposium. Chicago, Illinois,
      September 20-21, 1991.

PMID- 1362218
TI  - [Taxol and related diterpenoids of Taxus sp.: important acquisitions in the
      treatment of cancer].
AB  - Phytochemical and pharmacological studies on Taxus sp extracts have resulted in
      the isolation and the identification of several diterpenoids, and the discovery
      of the potent antitumor activity of taxol. This natural compound displays a
      unique mechanism of action as it stabilizes microtubules and inhibits their
      depolymerization into free tubulin. The emergence of taxol from the screening of
      natural products shows the benefits and the potent interest of these constituents
      in the search of drugs exhibiting novel mechanisms of action. The most pressing
      problem in taxol or taxol derivates commercialization is the drug supply.
      Alternative sources of taxol are now under investigation, mainly the total
      synthesis of taxol, the hemisynthesis of taxol or of taxotere from 10
      deacetylbaccatine III, the in vitro production of taxol by cell or tissue
      cultures, and the prospection of new natural sources of taxol.

PMID- 1362219
TI  - Receptor-mediated methylprednisolone pharmacodynamics in rats: steroid-induced
      receptor down-regulation.
AB  - Several approaches to receptor down-regulation were examined to extend previous
      receptor/gene-mediated pharmacokinetic/dynamic models of corticosteroids. Down
      regulation of the glucocorticoid receptor was considered as an instantaneous
      event or as a gradual steroid-receptor-mediated process. Concentrations of plasma
      methylprednisolone, free hepatic cytosolic receptors, and the activity of hepatic
      tyrosine aminotransferase (TAT) enzyme were measured for 16 hr following
      administration of 0, 10, and 50 mg/kg methylprednisolone sodium succinate to 93
      adrenalectomized rats. Receptor down-regulation was best described by a
      fractional decrement in the rate of return of free cytosolic glucocorticoid
      receptor. Predicted values for free receptor, bound receptor, nuclear bound
      receptor, and transfer compartments were in accord with the expected rank order
      values based on the high and low steroid doses. Model parameter estimates were
      independent of dose and described the rapid depletion of free cytosolic receptor,
      late-phase return of cytosolic receptor to a new baseline level that was 20-40%
      lower than control, and the TAT induction/dissipation pattern following steroid
      dosing. The microscopic association and dissociation constants describing the
      steroid-receptor interaction were 0.23 L/nmole per hr (k(on)) and 4.74 hr-1
      (k(off)) for methylprednisolone compared to previously obtained values of 0.20
      L/nmole per hr and 15.7 hr-1 for the related steroid prednisolone. The time
      course of TAT induction was similar to that observed previously for prednisolone.
      Efficiency of TAT induction was more closely related to steroid receptor
      occupancy than plasma methylprednisolone concentrations due to receptor
      saturability and receptor recycling.

PMID- 1362220
TI  - Linkage analysis with chromosome 15q11-13 markers shows genomic imprinting in
      familial Angelman syndrome.
AB  - Angelman syndrome (AS) and Prader-Willi syndrome (PWS) have become the classical
      examples of genomic imprinting in man, as completely different phenotypes are
      generated by the absence of maternal (AS) or paternal (PWS) contributions to the
      q11-13 region of chromosome 15 as a result of deletion or uniparental disomy.
      Apparently, most patients are sporadic cases. The genetic mechanism underlying
      familial AS has remained enigmatic for a long time. Recently, evidence has been
      emerging suggesting autosomal dominant inheritance of a detectable or
      undetectable defect in a gene or genes at 15q11-13, subject to genomic
      imprinting. The present report describes an unusually large pedigree with
      segregation of AS through maternal inheritance and apparent asymptomatic
      transmission through several male ancestors. Deletion and paternal disomy at
      15q11-13 were excluded. However, the genetic defect is still located in this
      region, as we obtained a maximum lod score of 5.40 for linkage to the GABA
      receptor locus GABRB3 and the anonymous DNA marker D15S10, which have been mapped
      within or adjacent to the AS critical region at 15q11-13. The size of the
      pedigree allowed calculation of an odds ratio in favour of genomic imprinting of
      9.25 x 10(5). This family illustrates the necessity of extensive pedigree
      analysis when considering recurrence risks for relatives of AS patients, those
      without detectable deletion or disomy in particular.

PMID- 1362221
TI  - Association between schizophrenia and homozygosity at the dopamine D3 receptor
      gene.
AB  - Disturbances in dopamine neurotransmission have been postulated to underlie
      schizophrenia. We report data from two independent studies of a BalI polymorphism
      in the dopamine D3 receptor gene in patients with schizophrenia. In both studies,
      more patients than controls were homozygous (p = 0.005, p = 0.008). When pooled
      data were analysed, this difference was highly significant (p = 0.0001) with a
      relative risk of schizophrenia in homozygotes of 2.61 (95% confidence intervals
      1.60-4.26).

PMID- 1362222
TI  - A new mutant transthyretin (Arg 10) associated with familial amyloid
      polyneuropathy.
AB  - We report a new kindred with systemic amyloidosis presenting as peripheral
      neuropathy in the sixth and seventh decades of life. Polymorphism in exon 2 of
      the transthyretin (TTR) gene was suggested by single strand conformation
      polymorphism analysis and determined by direct DNA sequencing. We also developed
      restriction fragment length polymorphism analysis by polymerase chain reaction
      using a primer with an induced mutation. The point mutation (cytosine for thymine
      at position 1038 of the TTR gene) is responsible for substitution of arginine for
      cysteine at position 10 of the TTR molecule. It is hypothesised that the TTR
      molecules which have no cysteine have a unique structure in heterozygous TTR
      polymers and are responsible for amyloid fibril formation.

PMID- 1362223
TI  - Quantitative Southern blot analysis in the dystrophin gene of Japanese patients
      with Duchenne or Becker muscular dystrophy: a high frequency of duplications.
AB  - Eighty-four unrelated patients with Duchenne or Becker muscular dystrophy in
      Japan were studied by quantitative Southern blot analysis with dystrophin cDNA
      probes. We found partial deletions and duplications in 47 (56%) and 12 (14%)
      cases respectively by HindIII digestion. The duplications were confirmed by BglII
      digestion and densitometric scanning. The frequency of duplications in this study
      is significantly higher than those previously reported. This may be because of
      the small sample number, the racial difference, or our quantitative methods. Our
      results suggest that attempts to detect duplications are important for a precise
      diagnosis. Both deletions and duplications clustered at the two hot spots as
      reported previously. Six cases were exceptions to the 'reading frame hypothesis'.
      We detected three types of HindIII RFLP. Based on the results of one duplication
      case, we propose a revised sequential order of exons in the cDNA10 region of the
      dystrophin gene.

PMID- 1362224
TI  - Presymptomatic diagnosis of von Hippel-Lindau disease with flanking DNA markers.
AB  - Von Hippel-Lindau (VHL) disease is a dominantly inherited cancer syndrome
      characterised by the development of retinal, cerebellar, and spinal
      haemangioblastomas, renal cell carcinoma, and phaeochromocytoma. The gene for VHL
      disease has been mapped to chromosome 3p25-p26 and flanking markers identified.
      We have investigated the usefulness of currently available DNA markers for the
      presymptomatic diagnosis of VHL disease. In the first part of this investigation,
      genetic linkage data from two previously published studies were updated and
      reanalysed to provide accurate estimates of sex specific recombination fractions
      and to confirm that there is no evidence of locus heterogeneity. In the second
      part of this study, 14 families containing 23 asymptomatic subjects at 50% prior
      risk of VHL disease were investigated with closely linked DNA markers (RAF1,
      D3S18, D3S732). Seventeen subjects were informative with one or more markers, six
      of whom were informative at markers flanking the VHL disease gene. By combining
      age related and DNA based risk information the carrier risk for 11 subjects was
      reduced to < 2%.

PMID- 1362225
TI  - Angelman syndrome with a chromosomal inversion 15 inv(p11q13) accompanied by a
      deletion in 15q11q13.
AB  - A family is described in which an inversion of chromosome 15, 15 inv(p11q13), is
      segregating. All family members are healthy except the proband who is a 10 year
      old boy with Angelman syndrome. Although the chromosomal inversion has been
      passed from the grandfather to both his son and his daughter with no ill effect,
      passage from daughter to grandson has resulted in a deletion of chromosome 15
      material which is presumed to be the cause of Angelman syndrome in this boy. The
      probabilities of an inversion of this type being instrumental in causing the
      syndrome are discussed.

PMID- 1362226
TI  - Myocardial glutathione depletion impairs recovery of isolated blood-perfused
      hearts after global ischaemia.
AB  - This study was performed to determine whether depletion of myocardial glutathione
      would impair recovery of left ventricular function of blood-perfused, isolated
      hearts after reversible ischaemic injury. Cats were treated with either vehicle
      or buthionine sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine
      synthetase, the rate-limiting enzyme in the synthesis of glutathione. The feline
      isolated hearts were perfused with the blood of normal donor cats before and
      after 40 min of global myocardial ischaemia. The myocardial concentration of
      glutathione of the BSO group, 178 +/- 38 ng/mg tissue, was significantly less
      than that of the control group, 292 +/- 38 ng/mg tissue (P < 0.05). The peak left
      ventricular developed pressure (LVDP) 1 h after reperfusion, expressed as a
      fraction of the peak LVDP before ischaemia, was 0.87 +/- 0.10 for the control
      group and 0.64 +/- 0.08 for the BSO group (P = 0.05 vs. control). The peak left
      ventricular dP/dt after reperfusion, expressed as a fraction of the peak dP/dt
      before ischaemia, was 1.08 +/- 0.14 for the control group and 0.78 +/- 0.09 for
      the BSO group (P = 0.05 vs. control). The myocardial creatine kinase activity of
      the BSO group, 1046 +/- 46 U/g tissue, was not significantly different from that
      of the control group, 1038 +/- 17 U/g tissue (P = 0.87). Thus, depletion of
      myocardial glutathione resulted in impaired post-ischaemic contractile function
      that cannot be attributed to a greater extent of irreversible cell injury.

PMID- 1362227
TI  - Treatment of dual diagnosis patients: a relapse prevention group approach.
AB  - The authors describe the successful use of an adjunctive group psychotherapy for
      substance-abusing patients with major psychiatric disorders (bipolar,
      schizophrenia, schizoaffective, psychotic depression, and atypical psychosis).
      The group utilizes a psychoeducational approach that focuses on substance abuse
      causes and consequences, principles of recovery, and relapse prevention
      strategies. Eight patients with prolonged histories of abuse of cocaine, alcohol,
      marijuana, or other drugs were enrolled in this weekly group treatment at a
      community mental health center drug treatment program, while continuing in
      treatment with their current case manager or primary therapist. Six of the eight
      patients achieved periods of stable abstinence, documented by self-report, urine
      toxicology screens, continued group attendance, and improved social functioning.
      Case examples are utilized to illustrate the group process.

PMID- 1362228
TI  - Treatment of khat addiction.
AB  - The authors present two cases of khat addiction that were successfully treated
      with bromocriptine. Khat is a bush cultivated in the Mid East because of its
      highly stimulant effects. Its leaves contain a variety of sympathomimetics. While
      khat is rarely found in the U.S., American soldiers stationed in the Arabian
      peninsula may be exposed to it. Because of an alcohol interdiction during the
      current Persian Gulf crisis, these troops may be tempted to use this plant as an
      alternative recreational drug.

PMID- 1362229
TI  - [Possible role of cellular immunity against tubular basement membrane antigen
      (TBM) in gold nephropathy in rheumatoid arthritis patients].
AB  - Autoantibody formation and lymphocytes proliferative response to tubular basement
      membrane (TBM) antigen were examined to clarify the pathogenesis of gold
      nephropathy, in rheumatoid arthritis patients. The existence of tubulopathy was
      ascertained by urine protein analysis, electrophoresis and urine TBM antigen
      titration. Circulating antibody to human TBM antigen titrated by enzyme
      immunoassay was significantly elevated in patients with gold tubulopathy, and
      mitogenic stimulation with TBM antigen of peripheral lymphocytes specifically
      responded in the early stage after receiving gold, but then clearly decreased
      after the cessation of gold. But, when the lymphocytes had been passed through a
      nylon wool column, the reaction was remarkably high even in the later stage after
      receiving gold, suggesting that another suppressive population of lymphocytes
      became trapped in the nylon wool column. This evidence suggests that gold
      compounds definitely act as initiating and promoting agents, and the development
      of tubular disorders induced by gold are likely related to the cellular
      recognition of effector T cells to the TBM antigen, following the strong effect
      of gold on the cellular immune system.

PMID- 1362230
TI  - [A case of microscopic polyarteritis nodosa associated with myeloperoxidase
      antineutrophil cytoplasmic autoantibodies (MPO-ANCA)].
AB  - We report a case of microscopic polyarteritis nodosa associated with
      myeloperoxidase-antineutrophil cytoplasmic autoantibodies (MPO-ANCA). A 38 year
      old female was admitted to our hospital, because of proteinuria, recurrent
      pyrexia, polyarthralgia, abdominal pain and purpura. She had a history of severe
      pulmonary hemorrhage and 4 kg weight loss for 8 months. On admission perinuclear
      ANCA without cytoplasmic ANCA was detected by indirect immunofluorescence assay
      and MPO-ANCA was detected by enzyme linked immunosorbent assay. But anti-nuclear
      antibodies, immune complexes and anti-glomerular basement membrane antibodies
      were not detected. Renal biopsy showed necrotizing crescentic glomerulonephritis
      without immune deposits. Skin biopsy revealed leukocytoclastic vasculitis.
      Diagnosis of microscopic polyarteritis nodosa was made by these clinical and
      histological evidence of vasculitis. As renal failure progressed after admission,
      corticosteroid and cyclophosphamide administration were started. Renal function
      and other symptoms improved paralleled with decreased MPO-ANCA titer to normal
      values. It is suggested that MPO-ANCA may be closely related to the pathogenesis
      of microscopic polyarteritis nodosa and it may be a good serological marker for
      diagnosis and disease activity of this disease.

PMID- 1362232
TI  - Delayed suppressive effect of a low dose of caerulein on the grooming behavior
      induced by the D1-receptor agonist SKF 38393.
AB  - Caerulein (CLN, 0.8-80 micrograms/kg, s.c.) was administered to male rats 10 min
      or 24 hr before the injection of SKF 38393 (3 mg/kg, i.p.). The increased mouth
      movement and grooming behavior by SKF 38393 were suppressed dose-dependently by
      CLN 10 min before the SKF 38393. CLN at the dose of 0.8 micrograms/kg, given 24
      hr before the SKF 38393, suppressed the grooming behavior by SKF 38393. These
      findings suggest that a low dose of CLN, but not a high dose, had a delayed
      suppressive effect on the grooming behavior induced by an excess of D1-activity.

PMID- 1362231
TI  - Effects of morphine on responses of nociceptive ventrobasal thalamic neurons in
      diabetic rats.
AB  - The influence of diabetes on the effects of morphine on the responses of
      ventrobasal (VB) thalamic neurons to mechanical noxious stimuli were studied in
      chloral hydrate-anesthetized rats. Animals were rendered diabetic by an injection
      of streptozotocin (60 mg/kg, i.v.). Morphine (0.3 mg/kg), administered i.v.,
      produced a reduction in the responsiveness of VB thalamic neurons to noxious
      stimulation in control rats. This effect was reversed by naloxone. In contrast,
      the inhibitory effects of morphine on the nociceptive responses of VB thalamic
      neurons were significantly attenuated in diabetic rats, as compared with the
      controls. However, there were no significant differences in inhibitory potency
      between diabetic and control rats when morphine (30 nM) was administered
      intrathecally. It seems likely that these changes in the sensitivity of VB
      thalamic neurons to morphine are, to some extent, the source of the reduction in
      the analgesic efficacy of morphine in diabetic rats.

PMID- 1362233
TI  - [The effects of autonomic agonists on the female rabbits urethra--in vitro
      isovolumetric and isometric study].
AB  - To investigate the characteristics of adrenoceptors of the proximal urethra in
      female rabbits, we performed the in vitro isovolumetric urethral pressure study
      and isometric study with three parts of muscle strips of the proximal urethra
      (whole layers, inner layers and outer layers). Both alpha-1 and alpha-2 agonist
      caused dose dependent response in in vitro isovolumetric pressure study as well
      as in vivo study. However, the response of alpha-2 agonist in in vitro was small
      in magnitude compared to in vivo study, suggesting the influence of permeability
      of drugs from serosa to mucosa in in vitro whole urethra study. The response of
      the strips of inner layers to alpha-1 agonist is almost the same as that of outer
      layers and whole layers, while the response of inner layers to alpha-2 agonist is
      almost twice as that of other layers. These findings are suggestive of
      predominance of alpha-2 adrenoceptors mediating contractions in the inner layers
      of the proximal urethra in female rabbits. Alpha-2 adrenoceptors which probably
      are distributed in mucosal and submucosal layers may have an important role in
      the mechanism of urinary continence in female rabbits.

PMID- 1362234
TI  - [Microsurgical autotransplantation of abdominal testis].
AB  - A 32-year-old man who had bilateral non-palpable testis underwent microsurgical
      orchidopexy of the right abdominal testis. Inferior epigastric vessels were used
      for the recipient vessels. Ischemic time during the operation was 40 minutes.
      Postoperative doppler readings revealed excellent blood flow to the testis, and
      HCG-stimulating test revealed good response. Now, 2 years after surgery, no sign
      of atrophy is found.

PMID- 1362236
TI  - pBluescriptII: multifunctional cloning and mapping vectors.

PMID- 1362237
TI  - Physicians extenders will be prevalent in the year 2002.

PMID- 1362235
TI  - [Acute pain in surgery: the significance of a neglected problem].
AB  - Acute pain represents a significant problem in surgical patients. However, the
      management of acute pain in Germany is unsatisfactory, mostly because surgeons
      are not interested in the pain of their patients, and anesthesiologists do not
      give pain treatment on surgical wards. The aim of this article is therefore to
      point out the significance of the problem of "acute pain" for surgeons. Basic
      knowledge of the production, perception and projection of pain as well as the
      special aspects of acute versus chronic pain is mandatory. Every surgeon should
      know about the predictors of postoperative pain, including the surgical and
      anesthesiological factors and patient characteristics. Efficient management of
      acute pain requires knowledge of the clinical significance of pain and the
      different methods for assessment. It is not sufficient to know the methods and
      advantages of appropriate management of acute pain; one must also understand the
      dangers. Problems caused by the treatment of pain should be recognized from a
      clinical point of view. Surgeons must take a greater interest in the problem of
      "pain", which should lead to the establishment of new concepts in the management
      of acute pain in surgical patients.

PMID- 1362238
TI  - Fimbriation, hemagglutination and adherence properties of fresh clinical isolates
      of Branhamella catarrhalis.
AB  - This study investigated the fimbriation on 24 fresh clinical isolates of
      Branhamella catarrhalis by electron microscopy. All the strains were isolated
      from patients with respiratory infections. The Branhamella catarrhalis strains
      were classified into three groups according to the grade of fimbriation. Among
      these 24 strains the incidence of densely fimbriated, moderately fimbriated and
      sparsely fimbriated isolates were 12 (50%), 7 (29%) and 5 (21%), respectively.
      After five-times serial subculture on Brain Heart Infusion agar, the average
      number of fimbriae per bacteria was decreased from 174 to 114 in the densely
      fimbriated strain and from 48 to 10 in the moderately fimbriated strain.
      Moreover, 20% of the population became non-fimbriated in moderately fimbriated
      strain after the serial subculture. In strains with higher hemagglutination titer
      the number of fimbriae was significantly (P < 0.04) more than in strains with
      lower hemagglutination titer.

PMID- 1362239
TI  - Benzodiazepine prescribing and injecting drug users.

PMID- 1362240
TI  - Proceedings of the Matrix Metalloproteinase Conference. Sandestin Beach, Florida,
      September 11-15, 1989.

PMID- 1362241
TI  - Identification of Glu 646 of neutral endopeptidase 24-11 as a zinc binding
      residue.

PMID- 1362242
TI  - Role of protein kinase C in the modulation of multidrug resistance: expression of
      the atypical gamma isoform of protein kinase C does not confer increased
      resistance to doxorubicin.
AB  - Cross-resistance to anticancer drugs, termed multidrug resistance (MDR), is
      functionally associated with the expression of a plasma membrane, energy
      dependent, drug efflux pump termed P-glycoprotein (PGP), the product of the mdr1
      gene. We have shown previously that MCF-7 breast carcinoma cells transfected with
      the human mdr1 gene (BC-19 cells) exhibit greater MDR when stably transfected
      with protein kinase C alpha (PKC alpha). We now demonstrate that transfection of
      BC-19 cells with the gamma isoform of PKC (BC-19/PKC gamma cells), which is not
      normally present in BC-19 cells, does not confer increased resistance to
      doxorubicin, despite a 19-fold increase in PKC activity. All of the increased PKC
      activity is accounted for by PKC gamma and it is rapidly down-regulated by
      phorbol dibutyrate, within 15 min of treatment. Endogenous PKC alpha and PKC
      epsilon activities are not affected by phorbol dibutyrate. The cytotoxicity of
      doxorubicin was similar in BC-19/neo or BC-19/PKC gamma cells after either 2-hr
      or continuous drug exposure, and co-treatment with phorbol dibutyrate increased
      resistance to doxorubicin 4-fold in both cell lines. Phosphorylation of PGP was
      similar in both cell lines and drug accumulation was not affected by
      overexpression of PKC gamma. These results demonstrate that transfection of PGP
      expressing cells with an atypical isoform of PKC does not confer increased MDR,
      and they suggest that the regulation of PGP is phenotype specific with respect to
      the isoform of PKC.

PMID- 1362243
TI  - Molecular cloning and expression of a pituitary somatostatin receptor with
      preferential affinity for somatostatin-28.
AB  - Using the polymerase chain reaction technique with degenerative primers, we
      obtained from a rat pituitary cDNA library a cDNA fragment, rAP236, that
      exhibited considerable homology to known receptors that belong to the guanine
      nucleotide-binding protein (G protein)-coupled receptor superfamily.
      Oligonucleotides to this fragment were used as probes to obtain a full-length
      cDNA from the rat pituitary cDNA library. This clone, rAP6-26, encoded a 383
      amino acid protein with seven putative transmembrane domains that are
      characteristic of G protein-coupled receptors. The predicted amino acid sequence
      of the rAP6-26 cDNA exhibits 56-66% homology to recently cloned somatostatin
      (SRIF) receptors. Membranes prepared from COS-7 cells transfected with the rAP6
      26 cDNA showed specific binding of 125I-Tyr11-SRIF, thus identifying the cDNA
      clone as a novel SRIF receptor. Radioligand binding competition analysis using
      somatostatin-28 (SRIF-28) and a number of cyclic SRIF analogs revealed that SRIF
      28 was the most potent competitor of 125I-Tyr11-SRIF binding, with a
      approximately 30-fold greater affinity for the receptor than that of SRIF. In
      addition, binding of 125I-Tyr11-SRIF was markedly reduced in the presence of Na+
      ions and GTP, indicating coupling of rAP6-26 receptors to inhibitory G proteins
      in COS-7 membranes. In adenylyl cyclase assays, forskolin-induced cAMP
      accumulation was inhibited by SRIF and SRIF-28, thus confirming that the rAP6-26
      cDNA encodes a functional receptor protein. By Northern blot analysis, a
      approximately 2.6 kilobase mRNA encoding the receptor was present in the
      pituitary but not in the liver, small intestine, kidney, pancreas, cerebellum, or
      cortex. Lack of receptor mRNA expression in the brain was confirmed by in situ
      hybridization histochemical studies. Thus, we report the cloning of a novel rat
      pituitary SRIF receptor, termed SSTR4, that has marked preferential affinity for
      SRIF-28 and is linked to inhibition of adenylyl cyclase.

PMID- 1362245
TI  - 3rd International Symposium on Lipid Metabolism in the Normoxic and Ischemic
      Heart. Rotterdam, The Netherlands, September 9-10, 1991.

PMID- 1362244
TI  - Inhibition by HS-142-1, a novel nonpeptide atrial natriuretic peptide antagonist
      of microbial origin, of atrial natriuretic peptide-induced relaxation of isolated
      rabbit aorta through the blockade of guanylyl cyclase-linked receptors.
AB  - HS-142-1, a specific nonpeptide antagonist for the atrial natriuretic peptide
      (ANP) receptor, equally blocked rat ANP (rANP)-, porcine brain natriuretic
      peptide-, or porcine C-type natriuretic peptide-stimulated GMP production in
      cultured bovine aortic smooth muscle (BASM) and bovine aortic endothelial (BAE)
      cells in a concentration-dependent fashion, at concentrations of 1-300
      micrograms/ml. But, even at 300 micrograms/ml, HS-142-1 only weakly inhibited the
      specific binding of 125I-rANP to the BASM and BAE cells, where only a small
      portion of the binding sites are linked to guanylyl cyclase. Further, with BAE
      cell membranes, HS-142-1 recognized only the 135-kDa ANP receptor, which is
      thought from 125I-rANP affinity cross-linking studies to be the guanylyl cyclase
      linked receptor. HS-142-1 also, if anything, inhibited the labeling of 135-kDa
      ANP receptors in the affinity cross-linking studies with BASM membranes,
      suggesting that a major portion of the 135-kDa ANP receptors are HS-142-1
      insensitive and only a small portion of the 135-kDa ANP receptors are responsible
      for the blockade by HS-142-1 of GMP production in BASM cells. At a concentration
      of 100 micrograms/ml, HS-142-1 reversibly prevented ANP-induced relaxation of the
      isolated rabbit thoracic aorta induced to contract with 3 x 10(-7) M
      phenylephrine, but not the relaxation induced by sodium nitroprusside,
      isoproterenol, or papaverine. These results suggest that HS-142-1 specifically
      inhibits natriuretic peptide-induced vasorelaxation through the blockade of
      guanylyl cyclase-linked natriuretic peptide receptors. HS-142-1 thus will be a
      powerful tool for understanding the physiological roles, in vasculature, of
      natriuretic peptides, which contribute to the homeostasis of blood pressure and
      intravascular volume.

PMID- 1362246
TI  - Studies on the interaction of leucocytes and the myocardial vasculature. I.
      Effect of hypoxia on the adherence of blood granulocytes.
AB  - Granulocytes play an important role in increasing the infarct size after ischemia
      and reperfusion by the release of oxygen-derived free radicals (ODFR) and
      lysosomal enzymes. It has been shown that the number of granulocytes adhering to
      the vascular endothelium increases after occlusion of the coronary artery, and
      that the area of myocardial damage can be reduced by preventing granulocyte
      adherence with monoclonal antibodies directed against adhesion receptors. The
      underlying mechanism of granulocyte activation under these conditions is not yet
      known. We have investigated whether granulocytes can be activated directly by
      reduced oxygen tensions. Granulocytes were suspended in a hypoxic buffer and
      incubated on fibronectin and gelatin coated microtitre plates at 1-3% ambient
      oxygen to study their ability to adhere to these matrices. The results showed
      that the adherence of granulocytes to fibronectin was dependent on the duration
      of hypoxia. After 30 min of incubation under hypoxia granulocyte adherence
      increased 1.3 to 1.8 fold compared to the normoxic control. The adherence to
      fibronectin could be inhibited partially by anti-CD18 antibody, a monoclonal
      antibody to the common beta chain of a class of extracellular matrix receptors.
      This direct activation of granulocytes due to hypoxic conditions may have
      implications for the interaction of these cells with the vascular endothelium in
      vivo.

PMID- 1362248
TI  - Single-strand conformation polymorphism (SSCP) analysis applied to the diagnosis
      of acute intermittent porphyria.
AB  - The single-strand conformation polymorphism (SSCP) technique was used to detect
      carriers of the known point mutation in the first exon of the porphobilinogen
      deaminase gene in Finnish and Swedish families. The SSCP technique was a reliable
      and convenient way of distinguishing patients from healthy members in a family.
      This point mutation is thought to result from a splicing defect of the mRNA. The
      PCR-based analyses of a patient's cDNA did not reveal the presence of an abnormal
      mRNA population, suggesting that no abnormal mRNA is synthesized or that it is
      too unstable to be detected.

PMID- 1362249
TI  - [Malaria prophylaxis].

PMID- 1362250
TI  - Application of magnetic resonance angiography to neurosurgical practice: a
      critical review of 150 cases.
AB  - The potential role of magnetic resonance angiography (MRA) in clinical
      neurosurgical practice was evaluated in 150 consecutive patients in an attempt to
      define clinical situations in which it aided in diagnosis, helped guide treatment
      options, and/or possibly eliminated the need for conventional catheter
      angiography. Among patients with nonvascular pathology (n = 42), MRA provided
      useful clinical information in 55% of cases, and could have effectively replaced
      catheter angiography in 76% of cases. In this group of patients, MRA provided
      excellent depiction of tumour and vessel relationships, and in conjunction with
      conventional imaging modalities reliably ruled out the question of tumour versus
      aneurysm whenever that question was raised. Among patients with vascular lesions
      (n = 108), MRA visualized the lesion in 18 of 20 (90%) aneurysms, 11 of 11 (100%)
      vascular malformations, 31 or 31 (100%) cases with known occlusive vascular
      disease, and reliably excluded occlusive vascular disease in 19 of 30 (63%)
      cases. The MRA potentially could have replaced conventional catheter angiography
      in less than 8% of cases with vascular pathology treated surgically, and in 76%
      of cases with vascular pathology treated medically or expectantly. Imaging time
      was relatively short, 10 to 20 minutes for intracranial vessels and 6.5 to 13
      minutes for extracranial vessels. Shortcomings included the lack of spacial
      resolution required for surgical planning and the possible misleading information
      in the settings of low flow and partial thrombosis. It is concluded that
      currently available MRA modalities contribute useful information in a wide
      spectrum of neurosurgical clinical situations including screening and serial
      follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362247
TI  - Occurrence and functions of the phosphatidylinositol cycle in the myocardium.
AB  - In the last decade a great deal of attention was awarded to a signal transduction
      pathway which is utilized primarily by 'Ca2+ mobilizing' signal molecules and
      which involves the hydrolysis of a quantitatively minor phospholipid,
      phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) by a PtdIns-specific
      phospholipase C (PLC). The evidence for the existence of receptor-mediated GTP
      binding protein-coupled PLC in myocardium and its possible functions are briefly
      summarized. The minireview is concentrated on the following aspects: 1) cellular
      localization and synthesis of polyphospho-PtdIns from PtdIns, 2) desensitization
      of the alpha 1-adrenergic agonist and endothelin-1 mediated PtdIns responses, 3)
      oscillatory Ca2+ transients initiated by PtdIns(4,5)P2 hydrolysis, 4)
      polyunsaturated fatty acids as constituents of polyphospho-PtdIns and of the
      protein kinase C activator 1,2-diacylglycerol (DAG), 5) source other than
      PtdIns(4,5)P2 contributing to the stimulated DAG, 6) role of the PtdIns pathway
      in cardiomyocyte growth and gene expression during the hypertrophic response.

PMID- 1362252
TI  - Introduction of high definition television system to neurosurgical documentation.
AB  - The high definition television (HDTV) system is introduced to microneurosurgery.
      Five cases with intracranial lesions: three cerebral aneurysms (giant aneurysms
      of the anterior communicating artery and internal carotid artery, aneurysm of the
      basilar artery), one acoustic neurinoma and one skull base meningioma, were
      operated on under the microscope using the HDTV system. The surgical procedures
      of each case were relayed and recorded by the system. In two of the five cases,
      we used two sets of HDTV system to produce stereoscopic projection. The HDTV
      system provided us with images of superior quality with a distinctly greater
      resolution than ordinary video systems.

PMID- 1362251
TI  - Differential expression of heat shock protein 70 gene between the cortex and
      caudate after transient focal cerebral ischaemia in rats.
AB  - In relation to changes of total protein synthesis, induction of 70-kDa heat shock
      protein (HSP70) mRNA was examined by Northern blot and in situ hybridization
      after 30 min of transient middle cerebral artery (MCA) occlusion of rats. HSP70
      mRNA was not present in the control condition of brain. With reperfusion, the
      mRNA was greatly induced along with the recovery of total protein synthesis in
      the cerebral cortex and lateral caudate of the ipsilateral hemisphere. However,
      the level of the mRNA reached a maximum earlier in the lateral caudate (at 3 h)
      than in the cortex (at 8 h), and the maximum amount of the mRNA was much smaller
      in the caudate than in the cortex. Total protein synthesis in the lateral caudate
      did not completely recover until 7 days. Histological examination showed a severe
      damage in cells of lateral caudate, while cells in the cortex were almost normal
      at 7 days. No difference in the brain temperature was observed between the two
      regions. These results show that the induction of HSP70 mRNA correlates with the
      recovery of protein synthesis in brain cells after a transient ischaemia, and
      that the HSP70 gene expression is different at the transcriptional level between
      the cortical and caudate cells after the transient ischaemia.

PMID- 1362253
TI  - Morphological quantitative analysis of intracranial pressure waves in normal
      pressure hydrocephalus.
AB  - This work presents a prospective morphological and quantitative analysis of 43
      intracranial pressure recordings performed on normal pressure hydrocephalic
      patients. This analysis led us to separate Lundberg's B waves into different
      subtypes and to refine the definition of the 'Plateau' wave. Two B wave subtypes
      named Great Symmetrical wave and Intermediate wave appeared correlated with the
      surgical improvement. In addition, the degree of post-operative improvement was
      correlated with the frequency of Intermediate wave. An extended quantitative
      classification of intracranial pressure waves is proposed that can be used alone
      to determine which patients should undergo a shunting procedure and which one
      should the most improve.

PMID- 1362254
TI  - Activation of phospholipase D by platelet-derived growth factor (PDGF) in rat C6
      glioma cells: possible role in mitogenic signal transduction.
AB  - The effects of platelet-derived growth factor (PDGF) on phospholipase D (PLD)
      activity and deoxyribonucleic acid (DNA) synthesis in rat C6 glioma cells have
      been investigated. Pretreatment of serum-starved C6 cells with PDGF results in
      enhanced choline production and the phosphatidylethanol (PEt) formation in the
      presence of ethanol, indicating the activation of PLD acting on
      phosphatidylcholine (PC). The dose-response curve for choline generation and DNA
      synthesis were comparable. In addition, the effects of PDGF on both PEt formation
      and [3H]thymidine incorporation into acid-precipitable material was blocked by
      the potent protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulphonyl)-2
      methylpiperazine (H-7) but not by N-(2-guanidinoethyl)-5-isoquinolinesulphonamide
      (HA1004), a relatively weak inhibitor of PKC, suggesting that PDGF plays an
      important role as a positive regulator of glioma cell growth via a PLD-mediated
      mitogenic signal transduction cascades, which depends largely on the activation
      of PKC.

PMID- 1362255
TI  - Leukotriene C4 contents, synthase and catabolic activity in human meningiomas.
AB  - Leukotriene has been proposed as a factor of tumour induced brain oedema.
      Independently of its size, meningioma occasionally shows various extents of
      peritumoural oedema. We investigated LTC4 tissue contents, LTC4 catabolic and
      synthetic activity in 12 human meningiomas and their correlation with
      peritumoural oedema was studied. LTC4 contents were varied from 0.01 to 8.21
      pg/mg tissue. When LTA4, an unstable expoxide intermediate was incubated with
      tumour homogenate, LTC4 was rapidly synthesized. However, LTC4 levels generated
      by incubating LTA4 with each homogenate were much different in each case.
      Degradation of LTC4 to LTD4, LTE4, and other polar materials was also rapid by
      incubation with tumour homogenates. Approximately 70% of added LTC4 was
      transformed to LTD4, LTE4 nor 6-trans LTB4 diastereoisomers during 30 min
      incubation at 37 degrees C. The results suggested that there were significant
      LTC4 tissue contents and LTC4 synthetic and catabolic activity in meningiomas.
      Oedema index ranged from 1.0 (no peritumoural oedema) to 67.5. No significant
      correlation, however, was observed not only between the LTC4 tissue contents and
      LTC4 synthetic or catabolic activities but also between each of these three
      parameters and peritumoural oedema. Thus, these results do not support a
      significant correlation of sulfidopeptide LTs with oedema formation in meningioma
      patients. Since leukotrienes are extremely unstable compounds, LTC4 tissue
      contents should be carefully discussed along with a consideration of rapid LTC4
      synthesis and catabolism. Further role of leukotrienes in meningioma tissue
      should be studied.

PMID- 1362256
TI  - Reversibility of energy metabolism and intracellular pH after cerebral ischaemia
      evaluated by 31P-MRS.
AB  - We have previously developed a reproducible model of transient forebrain
      ischaemia in rats by bilateral carotid artery occlusion combined with temporary
      increase of ICP. With this model, reversibility of the energy metabolism and
      intracellular pH (pHi) was investigated by 31P-MRS during 120 min of
      recirculation in three groups of, respectively, 30, 60, and 120 min of ischaemia.
      With the induction of ischaemia, ATP and phosphocreatine (PCr) disappeared, and
      measurement of pHi showed severe acidosis in all rats. In the 30 min ischaemia
      group, both energy metabolism and pHi recovered almost completely. In the 60 min
      ischaemia group, ATP recovered to 74% of control values, but pHi showed full
      recovery. In the 120 min ischaemia group, ATP recovered to about 50% of control
      values, and recovery of pHi was variable. Showing logarithmical changes during
      recirculation in ATP and PCr, the rate of metabolic recovery was fast during 60
      min of recirculation, but it decreased and reached plateau thereafter in all
      groups. Recovery of pHi was affected by ATP levels, and was precipitously
      accelerated as ATP levels exceeded 50% of pre-ischaemic values. These results
      suggest that prolongation of the duration of ischaemia limits the restoration of
      the energy state, and the quality of pHi recovery after cerebral ischaemia is
      affected by the degree of ATP recovery during 60 min of recirculation.

PMID- 1362257
TI  - Cerebral venous system mechanics during a constant infusion in subarachanoid
      space: a model study.
AB  - A model has been developed to explain the development of stress under a constant
      infusion of fluid into the subarachanoid space. When the regulatory mechanism
      operates, the infused fluid is accommodated by the venous system and hence the
      tissue 'give' mechanism is under minimal stress. The necessity of maintaining a
      constant blood flow causes the blood vessel to dilate at higher CSF pressures.
      This puts the tissue 'give' mechanism under dual pressures, since it has to make
      room for the expanding ventricle as well as the dilating venous system. The
      theoretical model developed has been validated by experimental observations.

PMID- 1362258
TI  - Fenestration of the middle cerebral artery and aneurysm at the site of the
      fenestration.
AB  - The authors report the case of a patient who presented a ruptured aneurysm of the
      anterior communicating artery and an unruptured aneurysm of the middle cerebral
      artery arising at the site of a fenestration of the MCA. The fenestration was
      undiagnosed on the preoperative angiogram but discovered during the surgery
      carried out for clipping of the aneurysms. In the literature, cases of
      fenestration of the MCA are sporadically reported and are incidental findings; an
      aneurysm may be associated on an artery other than the fenestrated MCA; an
      aneurysm arising at the site of the MCA fenestration is a very rare occurrence.

PMID- 1362259
TI  - Role of the time interval in the effect of neurochemical signals in the changes
      in the ultrastructure of cortical synapses.

PMID- 1362260
TI  - Dependence of the ultrastructural changes in cortical synapses on the time
      interval between associated neurochemical signals.

PMID- 1362261
TI  - Renal amyloidosis complicating Takayasu's arteritis: a rare association.

PMID- 1362262
TI  - Somatostatin is altered in developing retina from ethanol-exposed rats.
AB  - Optic nerve hypoplasia is seen in 50% of patients diagnosed with fetal alcohol
      syndrome and is due to a defect in the development of retinal ganglion cells.
      Somatostatin may influence the development of retinal ganglion cells, so we
      studied the effect of in vivo ethanol exposure on somatostatin expression in the
      developing retina. Somatostatin concentration is increased in retina from ethanol
      exposed fetuses and pups and this increase in peptide is associated with
      excessive neurite formation and improper migration of the somatostatin-containing
      neurons at early postnatal ages. These disturbances may account for the eventual
      failure in retinal ganglion cell development that results in optic nerve
      hypoplasia.

PMID- 1362263
TI  - Responses to repetitive afferent activity of rat solitary complex neurons
      isolated in brainstem slices.
AB  - The response of postsynaptic solitary complex neurons to repetitive stimulation
      (20-50 Hz) of the tractus solitarius were investigated by intracellular
      recordings in a brainstem slice preparation. Short duration stimuli (0.5 s)
      elicited increases in synaptic activity and short-term potentiation of synaptic
      potentials, both of which lasted approximately 1 min, plus a 10 s repolarization
      suppressed in the presence of glutamate ionotropic receptors antagonists 6-cyano
      7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and 2-D-amino-7-phosphonoheptanoic
      acid (AP7, 50 microM). Longer (5 s) stimuli elicited 2-10 min depolarizations
      accompanied by membrane resistance increases and unaffected by glutamate
      ionotropic receptors antagonists. Our study reveals several mechanisms by which
      rhythmic visceral afferents may exert a tonic control of postsynaptic solitary
      complex neurons.

PMID- 1362264
TI  - Somatostatin effects on cultured human fetal epiphyseal chondrocytes.
AB  - Somatostatin effects on cultured human fetal epiphyseal chondrocytes were
      evaluated by studying the effects of somatostatin on DNA synthesis. Cultured
      epiphyseal chondrocytes from human fetuses (12-40 wk old) were incubated for 48 h
      in Ham's F-12 serum-free medium. After this, the medium was replaced by MCDB-104
      serum-free medium and the cells were incubated for an additional 48 h in the
      presence or absence of somatostatin 1 pM to 10 microM, with the addition of 3H
      thymidine (5 microCi/mL) for the last 24 h of incubation. A significant (p <
      0.02) inhibitory effect of somatostatin (1 nM to 10 microM) on 3H-thymidine DNA
      incorporation was observed in cultured chondrocytes from fetuses of all
      gestational ages studied (12-40 wk), with no significant differences among fetal
      ages. In conclusion, our results show that somatostatin exerts a biologic effect
      on cultured human fetal epiphyseal chondrocytes, as it does in its target cells.
      These results suggest that somatostatin could regulate human skeletal growth not
      only by growth hormone secretion regulation, but also by acting directly on
      chondrocyte metabolism. However, the physiologic significance of the latter
      remains to be elucidated.

PMID- 1362266
TI  - [Treatment of prostatodynia (prostatosis].

PMID- 1362267
TI  - Astra Award Lecture. The psychopharmacology of 5-HT3 receptors.
AB  - 5-HT3 receptors have an exclusive neuronal location and evidence is presented of
      their involvement in behaviour. 5-HT3 receptor antagonists such as ondansetron,
      tropisetron and zacopride have provided the critical pharmacological tools to
      reveal a potent and efficacious ability to regulate disturbed behaviour. Thus the
      5-HT3 receptor antagonists will restore to normal rodent and primate behaviour
      disturbed by increasing limbic dopamine function, aversive situations, cognitive
      impairments and drug abuse. The remarkable feature of their action is a failure
      to modify normal behaviour. This unique pharmacological signature has ensured a
      wide interest in the potential role of the 5-HT3 receptor antagonists in the
      treatment of schizophrenia, anxiety, age related memory impairment and the
      problems of withdrawal from drugs of abuse. The preclinical data and preliminary
      clinical observations are presented.

PMID- 1362265
TI  - Selectivity and potency of opioid peptides in regulating human chorionic
      gonadotropin release from term trophoblast tissue.
AB  - The in vitro effect of three opioid peptides on hCG release from term trophoblast
      tissue was investigated. These peptides were prototypic for opioid receptors of
      the following types: kappa [dynorphin(1-13)], mu (DAMGO) H-Tyr-D-Ala2-Gly-N-Me
      Phe-Gly5- ol, and delta (DPDPE) H-Tyr-O-Pen-Gly-Phe-D-Pen-OH[D-Pen2,D
      Pen5]enkephalin. All peptides stimulated hCG release and their concentration
      response curves were bell shaped. Their order of potency was kappa >>> mu >
      delta. Stimulation of hCG release by any of the peptides was totally reversed by
      opioid antagonists, indicating that the action of peptides is mediated by
      placental opioid receptors. In order to confirm the specificity of opioid
      regulation of hCG release, three nonopioid drugs (cocaine, nicotine, and
      isoproterenol), with binding proteins and receptors known to be present in
      trophoblast tissue membranes, were also investigated. Stimulation of hCG release
      caused by certain concentrations of nonopioid drugs was not reversed by opioid
      antagonists, demonstrating that their effect is not mediated by opioid receptors.
      Furthermore, the concentration-response curve of isoproterenol was biphasic,
      suggesting the presence of a mechanism regulating hCG release that is not
      mediated by placental beta-adrenergic receptors. Data presented in this
      manuscript indicate that placental opioid receptors mediate one of the mechanisms
      regulating hCG release from trophoblast tissue and confirm our earlier results
      using opioid drugs.

PMID- 1362268
TI  - Calcium entry blockade as a mechanism for chlordimeform-induced inhibition of
      motor activity in the isolated guinea-pig ileum.
AB  - Central and peripheral alpha 2-adrenoceptors, including those of the
      gastrointestinal tract, have been indicated as a toxicity target of formamidine
      pesticides in mammals. In this study, the inhibitory effect of chlordimeform on
      twitch contractions from electrically-stimulated longitudinal muscle-myenteric
      plexus preparations (LMMPs) of the guinea-pig ileum was found to be resistant to
      the action of the alpha 2-adrenoceptor antagonist idazoxan. This drug was also
      ineffective on chlordimeform-induced inhibition of peristalsis recorded in whole
      ileal segments. As expected, idazoxan antagonized the inhibitory effect of the
      alpha 2-adrenoceptor agonist clonidine on twitch contractions and peristaltic
      activity. Chlordimeform reduced the amplitude of direct mechanical responses to a
      variety of spasmogens such as acetylcholine, histamine and substance P,
      suggesting a muscular site of action. Moreover, Ca(2+)-free, K(+)-depolarized
      LMMPs, chlordimeform inhibited submaximal contractions caused by addition of
      exogenous calcium, through an action apparently similar to that of the Ca2+ entry
      blocker nifedipine. Both chlordimeform- and nifedipine-induced inhibition of
      calcium contractions were reversed by the calcium channel activator BAY K 8644.
      This compound also partially prevented the inhibitory action of chlordimeform on
      peristaltic activity. On the whole, these results indicate that chlordimeform
      induced depression of motor activity in the guinea-pig ileum is, at least in
      part, related to inhibition of transmembrane Ca2+ fluxes responsible for smooth
      muscle contraction.

PMID- 1362269
TI  - The antibacterial effect of some neuroleptics on strains isolated from patients
      with meningitis.
AB  - Eighty-two strains of bacteria (Neisseria meningitidis, Haemophilus influenzae,
      Enterobacteriaceae, Streptococcus pneumoniae, group B streptococci and Listeria
      monocytogenes) were examined for their in vitro susceptibility to eight drugs,
      seven neuroleptics (perphenazine, fluphenazine, cis(Z)-clopenthixol, haloperidol,
      clozapine, clebopride and SCH 23390), and the neuroleptically inactive trans(E)
      clopenthixol. The phenothiazines and the thioxanthenes were, on the whole, the
      most active drugs when measured, the IC50(50) for each group of bacteria being
      7.4 to 84 mg/l (with the exception of the activity against the
      enterobacteriaceae). The antibacterial potency of clozapine, which has an
      atypical neuroleptic profile, was between 50 and 140 mg/l. Haloperidol also
      showed an antibacterial activity in the concentration range 35-140 mg/l. The
      selective D1 antagonist, SCH 23390 and the selective D2 antagonist, clebopride,
      inhibited only few of the bacteria in the concentration range investigated.

PMID- 1362270
TI  - The Biology and Pharmacotherapy of Manic-Depressive Disorders: From Molecular
      Theories to Clinical Practice. Satellite symposium to the XVIIIth CINP Congress.
      Copenhagen, Denmark, June 24-26, 1992.

PMID- 1362272
TI  - Manipulation of adiposity by somatotropin and beta-adrenergic agonists: a
      comparison of their mechanisms of action.

PMID- 1362271
TI  - beta-adrenoceptors in brain and pineal from depressed suicide victims.
AB  - beta-Adrenoceptors were measured by saturation binding of [3H]CGP 12177 in nine
      brain regions and pineal from suicides, with a firm retrospective diagnosis of
      depression, and age and sex matched controls. Twenty one suicides had not
      recently received antidepressant drugs, 17 had been receiving drugs prior to
      death. In antidepressant drug-free suicides, the number of total beta
      adrenoceptors was significant lower in temporal cortex (Brodmann area 38) and
      beta 1-adrenoceptors (Brodmann areas 21/22) was significant lower than matched
      controls. Suicides who died by violent means had significantly lower numbers of
      total beta- and beta 1-adrenoceptors in the frontal cortex and lower numbers of
      beta 1-adrenoceptors in temporal cortex (Brodmann areas 21/22) than matched
      controls. Suicides who died by non-violent means had lower numbers of total beta
      adrenoceptors in occipital cortex controls and lower numbers of total beta- and
      beta 1-adrenoceptors in temporal cortex (Brodmann area 38) than matched controls.
      In antidepressant drug-treated suicides, significantly lower number of beta
      adrenoceptor binding sites were found in temporal cortex (Brodmann area 38) and
      thalamus compared to matched controls. The lower number of beta-adrenoceptors
      binding sites in the thalamus appeared to be related to drug treatment. There
      were no differences in beta-adrenoceptor binding in the pineal gland between
      antidepressant-free and antidepressant-treated suicides and controls, although
      there were apparent differences between suicides and controls related to the time
      of death and season of death.

PMID- 1362274
TI  - 40th Annual Congress on Medicinal Plant Research. Trieste, 1-5 September 1992.
      Abstracts.

PMID- 1362273
TI  - Synthesis and H1-antihistaminic activity of beta-alkoxyethyl and beta-(N,N
      dialkylamino)ethyl-(3-aryl-3,4-dihydro-4-oxoquinazolin- 2-yl)m ethyl ethers.

PMID- 1362275
TI  - Biologic, pharmacologic, and psychosocial factors influencing response to
      neuroleptics.
AB  - Neuroleptic drugs remain a critical modality in the treatment of schizophrenia.
      Numerous variables influence response to neuroleptic drugs including biologic,
      pharmacologic, and psychosocial factors. This review cites some examples of how
      such factors have been examined.

PMID- 1362276
TI  - Tardive dyskinesia and diabetes mellitus.
AB  - Two studies examine the prevalence of tardive dyskinesia (TD) in neuroleptic
      treated diabetic patients. Study 1 compared 38 diabetic patients with 38
      nondiabetic patients treated for psychotic disorders with low to moderate doses
      of neuroleptics (mean chlorpromazine equivalents = 300 mg/day) for an average of
      18 years. Study 2 compared 24 diabetic and 27 nondiabetic patients treated for an
      average of 2.6 years with a mean 31 mg/day of metoclopramide for gastrointestinal
      disease. Patients were examined for TD using standardized scales by raters blind
      to all treatment and illness variables. In both studies, there were no
      differences between the diabetic and nondiabetic groups in age, sex, type of
      psychiatric illness, and dose and duration of neuroleptic treatment or severity
      of parkinsonism. In both studies, the diabetic patients had significantly greater
      prevalence and severity of TD. No measures of diabetes severity were associated
      with TD in either study. Possible pathophysiologic mechanisms for the increased
      prevalence of TD in neuroleptic-treated patients with diabetes will be discussed.

PMID- 1362277
TI  - Benzodiazepine augmentation of neuroleptics in treatment-resistant schizophrenia.
AB  - A significant minority of patients with schizophrenia fail to respond to
      neuroleptic medication alone. In some of these patients, adjunctive treatment
      with benzodiazepines may prove beneficial. Preclinical studies suggest that
      benzodiazepines significantly decrease brain dopamine release and turnover,
      perhaps by augmenting gamma-aminobutyric acid (GABA) inhibition of dopamine
      neuron activity. Double-blind clinical studies, however, have not conclusively
      established a role for benzodiazepines in the treatment of schizophrenia, and it
      seems likely that some patients respond favorably, whereas others do not. We
      review preliminary new observations that approximately half of a group of
      treatment-resistant patients, studied in a double-blind treatment protocol,
      demonstrated clinically significant antipsychotic responses to adjunctive
      alprazolam. We also briefly describe long-term efficacy of alprazolam in several
      patients whom we have followed in open-label clinical settings. Possible
      predictors or biological concomitants of benzodiazepine responsivity, which may
      aid in delineating distinct subgroups of patients, are discussed, and
      recommendations for future research are presented.

PMID- 1362278
TI  - The human hypothalamus in health and disease. Proceedings of the 17th
      International Summer School of Brain Research. Amsterdam, The Netherlands, 26-30
      August 1991.

PMID- 1362279
TI  - The hypothalamic lateral tuberal nucleus: normal anatomy and changes in
      neurological diseases.
AB  - The lateral tuberal nucleus is a circumscribed cell mass in the lateral posterior
      part of the hypothalamus, containing about 60000 neurons. It can be recognized in
      man and higher primates, probably not in other mammals. Its neurotransmitter
      content and connections with other parts of the brain are as yet unknown. But
      receptors for corticotropin-releasing factor and somatostatin, as well as
      muscarinic cholinergic receptors, benzodiazepine receptors and N-methyl-D
      aspartate receptors have been localized within the confines of the nucleus. The
      lateral tuberal nucleus is affected in a number of human neurodegenerative
      diseases. Changes in Parkinson's disease are the least obvious: Lewy bodies
      appear in small amounts, the majority of them apparently lying outside a neuronal
      perikaryon. Neuronal loss does not occur. In Alzheimer's disease the number of
      neurons seems to be normal as well. Rarely silver staining tangles occur, and the
      deposition of A4/beta-protein in amorphous plaques is moderate. Yet, NTL neurons
      stain heavily in Alz-50 immunocytochemistry, while Alz-50 staining in NTL
      neurites is very dense. These changes are interpreted as indicating early
      Alzheimer-related pathology. In Huntington's disease the NTL loses neurons. This
      loss is related to the severity of the disease: patients who first display motor
      disturbances at an early age will lose more neurons than those who start later.
      The relation between these clinical characteristics and the severity of neuronal
      loss is such, that it seems likely that NTL neurons possess a special
      vulnerability for the effect of the Huntington gene. This could be related to
      their NMDA-receptor content. It is hypothesized that the NTL is involved in a
      neuronal network that regulates feeding and metabolism. NTL pathology may explain
      the peculiar catabolic state of many patients with Alzheimer's or Huntington's
      diseases.

PMID- 1362280
TI  - The use of linkage analysis and the Centre d'Etude Polymorphisme Humain (CEPH)
      panel of DNA in the study of the arginine vasopressin, oxytocin and prodynorphin
      gene loci.

PMID- 1362282
TI  - The Interrelationship of Hodgkin's Disease and Non-Hodgkin's Lymphoma. Workshop.
      San Antonio, Texas, October 31-November 2, 1991.

PMID- 1362281
TI  - Prognostic value of kinetic parameters of HIV isolation from peripheral blood
      mononuclear cells.
AB  - To assess the correlations between clinical and biological stages of HIV
      infection and HIV isolation, peripheral blood mononuclear cells from 389 HIV
      infected patients were studied by 30-day cocultures with normal lymphocytes. HIV
      isolation was successful in 279/389 patients (71.7%). Positive isolation was more
      frequent in CDC IV cases (82%) than in CDC II and III cases (63.6% and 78.4%
      respectively). There was a close correlation between culture positivity and serum
      beta 2-microglobulin, CD4+ cell counts and serum p24 antigen. The day of peak
      detection of reverse transcriptase activity or peak p24 antigen in coculture
      supernatants was selected as a coculture kinetic parameter. The day of peak
      detection of HIV in culture occurred earlier in CDC IV cases than in CDC II and
      III cases, and was a prognostic factor in AIDS progression at 2 years. These data
      suggest that in vitro parameters related to both viral burden and replicative
      capacity of HIV isolates are relevant indicators of disease progression.

PMID- 1362283
TI  - The immunohistochemistry of Hodgkin's disease.
AB  - Immunohistochemistry is a valuable adjunct to the identification of Hodgkin's
      disease (HD) Reed-Sternberg (RS) cells, and in the differential diagnosis between
      HD, non-Hodgkin's lymphomas, and nonlymphoid neoplasms containing RS-like cells.
      The characteristic phenotype of RS cells in different subtypes of HD is
      described, with an emphasis on routine immunohistochemical stains. Some of the
      conflicting literature on this subject is reviewed to highlight pitfalls and
      controversies in the field.

PMID- 1362284
TI  - Localization of proliferating cell nuclear antigen (PCNA/Cyclin) in workshop
      cases of Hodgkin's disease and non-Hodgkin's lymphoma.
AB  - Proliferating cell nuclear antigen (PCNA/Cyclin) is a 36-kD protein that is
      present in cycling cells but not in resting cells, and therefore represents a
      marker of tumor proliferation. Application of anti-PCNA/Cyclin monoclonal
      antibodies has shown that this protein is localized to the nucleus of cycling
      cells, with the exception of cells in mitosis, which demonstrate faint
      cytoplasmic reactivity. Recently, Benjamin and Gown found that Reed-Sternberg
      cells and variants show nuclear and cytoplasmic staining with anti-PCNA/Cyclin
      antibody 19A2, and suggested that this feature may be useful in distinguishing
      Hodgkin's disease from other tumors. This report describes the reactivity of 42
      workshop cases that were stained with anti-PCNA/Cyclin antibodies 19A2 and/or
      PC10. Thirty-three (79%) of the 42 cases showed adequate reactivity to allow for
      interpretation of staining localization. In the group of reactive cases, 26 (79%)
      showed nuclear and cytoplasmic staining. The localization of PCNA/Cyclin was
      compared with the consensus diagnosis in each case. Eighty percent of cases
      classified as Hodgkin's disease, 67% of cases classified as non-Hodgkin's
      lymphoma, and 100% of unresolved cases showed both nuclear and cytoplasmic
      staining. The incidence of cytoplasmic PCNA/Cyclin was not different between
      Hodgkin's disease and non-Hodgkin's lymphoma in this study.

PMID- 1362285
TI  - The Symposium on Longitudinal Data Analysis. Fort Lauderdale, Florida, 19-21 June
      1991.

PMID- 1362286
TI  - [History of the discovery of gold salts action in rheumatoid polyarthritis].

PMID- 1362287
TI  - Blood and urinary cadmium levels in Inuit living in Kuujjuaq, Canada.
AB  - Blood and urine cadmium concentrations have been determined in a group of 85
      Inuit residents of Kuujjuaq, Quebec, Canada, drawn from actively hunting
      households. Mean blood cadmium values are high at 39.4 nmol/l, varying between
      6.6 in non-smokers and 60.3 in smokers. No association of blood cadmium with self
      reported offal consumption could be found. Median urine cadmium concentrations
      are elevated at 2.3 mumol/mol creatinine and rise substantially with age: 0.9 in
      the 30-39 age group; 3.2 among the 40-59 age group; and 4.1 in the 60 and over.

PMID- 1362288
TI  - [Clinical profile of ANCA-associated diseases].

PMID- 1362289
TI  - A review of the role of anti-opioid peptides in morphine tolerance and
      dependence.
AB  - Studies on the mechanisms of tolerance and dependence have mostly focused on
      changes at the receptor level. These experiments, conducted with model systems
      ranging from clonal cell lines to whole animals, have identified a number of
      important adaptive mechanisms which occur at the receptor level. However, none of
      these adaptive mechanisms can completely account for the phenomena which serve to
      define the state of morphine tolerance and dependence, especially the observation
      that as an animal becomes more tolerant to morphine, less naloxone is required to
      trigger withdrawal. The data reviewed in this paper provide strong support for
      the hypothesis that the brain synthesizes and secretes neuropeptides which act as
      part of a homeostatic system to attenuate the effects of morphine and endogenous
      opioid peptides. According to this model, administration of morphine releases
      anti-opioid peptides (AOP), which then attenuate the effects of morphine. As more
      morphine is given, more AOP are released, thereby producing tolerance to the
      effects of morphine. Cessation of morphine administration, or administration of
      naloxone, produces a relative excess of anti-opioid, which is in part responsible
      for the withdrawal syndrome. Since endogenous and exogenous antagonists might
      together produce synergistic effects, less naloxone might be required to trigger
      withdrawal in the presence of higher levels of AOPs. Although the study of AOP is
      in its infancy, a deeper understanding of the central nervous system (CNS) anti
      opioid systems may lead to new treatments for chronic pain, substance abuse, and
      psychiatric disorders.

PMID- 1362290
TI  - Comparison of chronic intermittent haloperidol and raclopride effects on striatal
      dopamine release and synaptic ultrastructure in rats.
AB  - The effects of chronic intermittent administration (7 months) of two
      neuroleptics, haloperidol (HAL) and raclopride (RAC), were compared using several
      different measures. Both drugs were administered weekly by subcutaneous injection
      at 7.0 mg/kg. Both neuroleptics consistently produced catalepsy throughout the
      treatment period, although HAL was generally more cataleptogenic than RAC.
      Assessment of dopamine (DA) release in the caudate putamen (CPu), through the use
      of in vivo microdialysis, showed that chronic HAL or RAC administration caused a
      prolonged decrease of DA release in response to a low dose of the DA D2 agonist
      quinpirole (0.03 mg/kg, sc). Injection of the muscarinic agonist pilocarpine (1.0
      mg/kg, IP) did not have any significant within-group effects, although both
      neuroleptic treatment groups showed decreased DA release when compared to
      controls. Ultrastructural analysis of the dorsolateral CPu showed that both HAL
      and RAC treatment resulted in a significant increase in the number of perforated
      synapses, which contain a discontinuous density along the postsynaptic membrane.
      These results demonstrate that two different DA D2 receptor antagonists produce a
      similar effect on DA function and ultrastructural changes within the CPu
      following chronic, intermittent treatment.

PMID- 1362291
TI  - The paradoxical effect of NMDA receptor stimulation on electrical activity of the
      sensorimotor cortex in freely behaving rats: analysis by combined EEG
      intracerebral microdialysis.
AB  - This study was designed to determine the effects of N-methyl-D-aspartate (NMDA)
      receptor stimulation on the electrical activity of neocortex in freely behaving
      rats. Electroencephalogram (EEG) recording and intracerebral microdialysis were
      conducted simultaneously in the same site of the sensorimotor cortex, where the
      basal extracellular concentrations of aspartate and glutamate were 2.1 +/- 0.7
      microM and 11.5 +/- 2.4 microM, respectively. Microdialysis with NMDA solutions
      (ranging from 10.0 microM to 10.0 mM) reduced the amplitude of the EEG activity
      and decreased the power of all frequency bands, with a virtual elimination of the
      high frequency waves, in a dose-dependent manner. These EEG changes were reversed
      after washing out the drug from the microdialysis fluid, and could be effectively
      antagonized with the competitive NMDA receptor antagonist DL-2-amino-5
      phosphonovalerate. Remarkably, the NMDA actions were not associated with
      epileptiform behavioral or electrographic events. Control studies demonstrated
      that in the same experimental conditions, cholinergic receptor agonist carbachol
      caused seizures, and microdialysis with NMDA in the hippocampus readily induced
      epileptiform spikes. Our study shows that NMDA receptor stimulation in the rat
      sensorimotor cortex, although excitatory at synaptic level, can depress the local
      EEG activity. This may indicate that the NMDA receptor-mediated signals are
      processed by the neocortical network in a different way than by many other brain
      circuitries including hippocampus.

PMID- 1362293
TI  - [The individual choice of anti-anginal preparations by using paired bicycle
      ergometry tests in patients with stenocardia].

PMID- 1362292
TI  - Fischer and Lewis rat strains differ in basal levels of neurofilament proteins
      and their regulation by chronic morphine in the mesolimbic dopamine system.
AB  - We studied levels of neurofilament (NF) proteins in the ventral tegmental area
      (VTA), and other regions of the central nervous system, of two genetically inbred
      rat strains, Lewis (LEW) and Fischer (F344) rats. These strains represent
      genetically divergent populations of rats that have been used to study possible
      genetic factors involved in a variety of biological processes, including drug
      addiction: compared to F344 rats, LEW rats show a much higher preference for
      several classes of drugs of abuse. We found 30-50% lower levels of three NF
      proteins, NF-200 (NF-H), NF-160 (NF-M), and NF-68 (NF-L), in the VTA of LEW
      compared to F344 rats by use of immunolabeling and Coomassie blue staining. These
      strain differences were highly specific to this brain region, with no differences
      observed elsewhere in brain or spinal cord. Interestingly, chronic treatment of
      F344 rats with morphine decreased levels of these three NF proteins in the VTA,
      as found previously in outbred Sprague-Dawley rats (Beitner-Johnson, D., Guitart,
      X., and Nestler, E.J.:J. Neurosci., 12:2165-2176, 1992), whereas morphine had no
      effect on NF levels in the VTA of LEW rats. A similar strain difference was
      observed in chronic morphine regulation of tyrosine hydroxylase, with morphine
      increasing enzyme immunoreactivity in the VTA of F344 rats (as has been observed
      previously in Sprague-Dawley rats [Beitner-Johnson, D., and Nestler, E.J.:J.
      Neurochem., 57:344-347, 1991]), but not in LEW rats. In view of the observations
      that LEW and F344 rats show different levels of preference for several types of
      drugs of abuse, and of the evidence supporting a central role of the mesolimbic
      dopamine system in drug reward mechanisms, the results of the current study
      suggest the possibility that levels of NFs and tyrosine hydroxylase may mediate
      some aspects of drug reinforcement and contribute to individual genetic
      differences in vulnerability to drug addiction.

PMID- 1362295
TI  - HLA class II nucleotide sequences, 1992.
AB  - The HLA Class II sequences included in this compilation are taken from
      publications listed in the papers: Nomenclature for factors of the HLA system,
      1991 (1), Nomenclature for factors of the HLA system, 1990 (2), and Nomenclature
      for factors of the HLA system, 1989 (3). Where discrepancies have arisen between
      reported sequences, the original authors have been contacted, where possible, and
      necessary amendments to published sequences have been incorporated into this
      alignment. Future sequencing may identify errors in this list and we would
      welcome any evidence that helps to maintain the accuracy of this compilation. In
      the sequence alignments, identity between residues is indicated by a hyphen (-).
      An unavailable sequence is indicated by an asterisk (*), gaps in the sequence are
      inserted to maintain the alignment between different alleles showing variation in
      amino acid number.

PMID- 1362294
TI  - HLA class I nucleotide sequences, 1992.
AB  - The HLA Class I sequences included in this compilation are taken from
      publications listed in the papers: Nomenclature for factors of the HLA system,
      1991 (1), Nomenclature for factors of the HLA system, 1990 (2), and Nomenclature
      for factors of the HLA system, 1989 (3). Due to the increased number of
      sequences, we have only included sequences for exons 2, 3 and 4 in this
      compilation. Where discrepancies have arisen between reported sequences, the
      original authors have been contacted where possible, and necessary amendments to
      published sequences have been incorporated into this alignment. Future sequencing
      may identify errors in this list and we would welcome any evidence that helps to
      maintain the accuracy of this compilation. In the sequence alignments, identity
      between nucleotides is indicated by a hyphen (-). An unavailable sequence is
      indicated by a period (.). Gaps in the sequence are inserted to maintain the
      alignment between different alleles showing variation in amino acid number.

PMID- 1362296
TI  - The B*4002 allele encodes the B61 antigen: B40* is identical to B61.

PMID- 1362297
TI  - [The determination of benzodiazepines in biological objects on the Milichrome
      microcolumn liquid chromatograph].
AB  - 1,4-benzodiazepines and benzophenols, the products of their hydrolytic cleavage,
      were measured by high-pressure liquid chromatography in expert material (stomach,
      liver, intestine, kidney samples). Milichrome microcolumn liquid chromatograph,
      designs 1 and 2, was employed, with a chromatography column packed with Separon
      C18 (5 microns) sorbent. A mixture of (NH4)2HPO4 (0.05 M) and acetonitryl in
      volume ratio 65:35 was used as the mobile phase in native compound analysis and
      that in volume ratio 45:55 for benzophenols and medazepam separation. The
      external standard method was used for quantitative estimation.

PMID- 1362299
TI  - The promise of taxol.

PMID- 1362301
TI  - WFUMB Symposium on Safety and Standardisation in Medical Ultrasound. Issues and
      Recommendations Regarding Thermal Mechanisms for Biological Effects of
      Ultrasound. Hornbaek, Denmark, 30 August-1 September 1991.

PMID- 1362298
TI  - [Studies of cerebrospinal fluid diagnosis in Alzheimer's disease: a review of the
      literature and of current developments].
AB  - Studies into the value of examination of the cerebrospinal fluid (CSF) in
      diagnosing Alzheimer's disease are reviewed. The diagnostic utility of about 60
      substances including CSF measures related to classical neurotransmitters,
      (neuro)peptides, proteins, amino-acids, trace elements, and constituents of
      senile plaques and neurofibrillary tangles is evaluated. Technical,
      methodological, and ethical issues relevant to this kind of studies are
      discussed. None of the CSF constituents studies so far, has a proven diagnostic
      utility. Increased knowledge concerning macromolecular changes in the brain and
      improved immunochemical techniques make the outlook for a diagnostic test for
      Alzheimer's disease on CSF promising.

PMID- 1362300
TI  - Quantitative Electron Microscopy. Workshop. 2-7 December 1991.

PMID- 1362303
TI  - Proceedings of the 2nd Congress of the European Society for Veterinary Virology.
      Uppsala, Sweden, 24-26 September 1991.

PMID- 1362302
TI  - [Comparative evaluation of the hypotensive effectiveness of beta blockers].
AB  - The hypotensive efficacies of timolol, vistagan, and betoptic were studied in
      three groups of patients with primary open-angle glaucoma, matched for the
      clinical diagnosis, somatic condition, and number of patients. The hypotensive
      activity of timolol was found superior to that of vistagan or betoptic, but its
      administration was associated with tachiphylaxia, that is an essential
      disadvantage of the drug. The advantage of vistagan and betoptic is the
      possibility of their administration to cardiopulmonary patients with
      contraindications against timolol therapy.

PMID- 1362305
TI  - [Self-care in the prevention of sudden cardiac death].
AB  - In acute myocardial infarction a third up to half of death registered within the
      first month occur in the first hour of the onset of attack most frequently
      because of ventricular fibrillation. Immediate self administration of drugs
      stabilizing electrically the heart may prevent it. On the basis of experiments in
      dogs and in rats flunitrazepam (Rohypnol tabl. 1 mg), tramadol (Tramal caps. 50
      mg) and the beta blocker metipranolol (Trimepranol tabl. 10 mg) were selected for
      clinical trial on high risk patients. As the chosen combinations of drugs were
      not yet tested in view of possible interactions, we studied their effect on
      circulation and cardiovascular reflexes in eight healthy volunteers. When the
      drugs were absorbed from the mouth mucosa, the decrease in the heart rate during
      deep breathing was observed already 15 minutes after the intake of drugs. The
      subjects started to feel relaxed; later on they had pleasant feelings and felt
      sleepy. There were no undesirable changes in the heart rate or blood pressure. In
      the three drug combination with metripranolol, the decrease in the heart rate was
      more marked. The tests in volunteers were without any undesirable effects and
      both combinations may, therefore, be given to selected high risk subjects, e g.
      convalescents from myocardial infarction. Randomized trial to prove the
      preventive effect already started.

PMID- 1362304
TI  - Analysis of T lymphocyte subsets proliferating in response to infective and UV
      inactivated African swine fever viruses.
AB  - The proliferative response to infective and UV-inactivated African swine fever
      virus was analyzed in cells from pigs surviving an experimental infection with
      attenuated virus. All the pigs showed strong dose-dependent proliferative
      responses to both infective and UV-inactivated virus. This response was also
      observed when nitrocellulose-bound solubilized virus proteins were used in the
      assay. Heterologous isolates also induced proliferation, however it was
      significantly lower than that induced by the isolate used to infect the animals.
      The response to infective virus was blocked equally by anti-CD4 and anti-CD8
      monoclonal antibodies (mAb); the response to UV-inactivated virus was almost
      abolished by anti-CD4 and 60% inhibited by anti-CD8 mAb. FACS analysis of 28-day
      T cell lines derived from peripheral blood mononuclear cells demonstrated the
      progressive increase of the CD8+ subset when the cells were stimulated with
      infective virus, whereas the stimulation with UV-inactivated virus induced the
      increase of both CD4+ and CD8+ subsets. In this case, the sum of CD4+ and CD8+
      percentages was higher than the total percentage of T cells, suggesting the
      presence of cells positive for both CD4+ and CD8+.

PMID- 1362307
TI  - [Carcinoma in situ in cryptorchid testes in post-pubertal patients].
AB  - The pathohistologic analysis of testis sections of 37 postpuberty patients with
      different types of cryptorchism is performed. The tissue samples were taken
      during orchiopehy, fixed in Bouin's solution and treated by the standard
      histologic techniques. The morphologic criteria are presented for identification
      of the presence of the so called carcinoma in situ cells found in two cases.
      Besides, in 13 patients rare, mainly single, atypical germinative cells were
      found in a smaller number of the seminiferous tubules. It has been concluded that
      the presence of carcinoma in situ cells in undescended testes of some patients
      and considering the simple way of sampling, lack of complications and high
      reliability of the diagnostic procedure, it is absolutely justified to take
      routine biopsy of testes during orchiopexy in each postpuberty and perhaps
      prepuberty patient.

PMID- 1362306
TI  - [Multiple endocrine neoplasia type 2: familial variant of medullary carcinoma of
      the thyroid gland].
AB  - In addition to a brief characteristic of the syndrome of multiple endocrine
      neoplasia type 2 and medullary thyroid carcinoma with a familial incidence which
      is a prerequisite of the syndrome, the authors submit an account on a group of 53
      patients who were on the authors' records during the past 12 years. During this
      period the disease is systematically searched for in the families of newly
      diagnosed patients by examining the immunoreactive calcitonin level of relatives.
      Familial variants account for 28% of all medullary thyroid carcinomas. Patients
      who are on the records so far belong to 24 families. Approximately twice as often
      an isolated variant of the familial type of medullary carcinoma is involved, as
      compared with association with another endocrine affection, in particular
      pheochromocytoma (Sipple's syndrome), but associated forms will increase in
      number perspectively (multiple endocrine neoplasia 2A). The syndrome of multiple
      endocrine neoplasia 2B is very malignant but in view of the typical phenotype the
      disease should be diagnosed already before the change to malignancy--once the
      disease develops into the clinical stage the course is very adverse. From the
      original number of all familial tumours 38 subjects survive (72%), incl 22 who
      were subjected to bilateral total thyroidectomy based on screening in the
      preclinical stage. The prognosis of these individuals is very favourable, the
      calcitonin levels are throughout the follow-up period (2-10 years) repeatedly
      negative. With regard to the possible association with another endocrinopathy
      (pheochromocytoma or hyperparathyroidism) all must be followed up systematically
      (screening) with regard to the manifestation of an associated endocrinopathy
      frequently only after a longer time interval.

PMID- 1362308
TI  - [Dopaminergic regulation of the renin-angiotensin-aldosterone system (RAAS). The
      control of the initial components of the RAAS (a review of the literature)].

PMID- 1362310
TI  - [Diagnostic reference. Human immunodeficiency virus].

PMID- 1362312
TI  - [Report of the scientific symposium: bolus tocolysis in theory and practice. 29
      30 May 1992 at the Herne Marien Hospital University Gynecologic Clinic, Bochum
      Ruhr University].

PMID- 1362309
TI  - [Vibrio cholerae toxin B subunit gene expressed in a Salmonella vaccine strain].
AB  - This paper reports that the V. cholerae toxin B subunit (ctx B) gene was inserted
      into pYA 248 plasmid with the aspartate beta-semialdehyde dehydrogenase (asd)gene
      and the recombinant plasmid was transformed into S. typhimurium deleting asd
      gene. Results showed that ctx B gene was highly expressed and secreted into
      midium. This strain was able to colonize in the intestinal epithelium. Oral
      immunity and general immunity could produce antibodies at high level and enhance
      cellular immune responses. The animals orally inoculated with S. typhimurium x
      4072 (pYA-ctx B) vaccine had remarkable protection against virulent V. cholear
      569B strain and S. typhimurium strain. Use of such system provides useful method
      for oral vaccine.

PMID- 1362311
TI  - [Conditioned reflexes and memory in the honey bee].

PMID- 1362313
TI  - [The effect of fenazepam on the humoral immune response in secondary
      immunodeficiency].
AB  - A single administration of phenazepam (2.5 mg/kg) enhances the synthesis of
      antibodies after immunization with different vaccines. Phenazepam restores
      antibody formation in immunodeficiency induced by intoxication. The
      immunostimulating effect of phenazepam is linked with an increase in the capacity
      of macrophages for inducing humoral immune response and a rise in the number of
      antibody-producing cells in the spleen.

PMID- 1362314
TI  - Limbic seizure-induced changes in extracellular amino acid levels in the
      hippocampal formation: a microdialysis study of freely moving rats.
AB  - Limbic seizure-activity was induced by injecting kainic acid into the amygdala of
      rats. Extracellular levels of amino acids were monitored by microdialysis in the
      hippocampus. No changes were detected in the levels of glutamate and aspartate.
      The level of glycine also remained unchanged, whereas GABA showed an increase of
      approximately 35%. The level of glutamine decreased by approximately 30%, and
      that of serine by approximately 20%. The results indicate that increased turnover
      may exist in the glutamate transmitter pool. In addition, impairment of GABA
      release seems not to be a pathogenetic factor in seizure-induced hippocampal
      neuron loss. It is concluded that even during sustained seizure-activity, the
      extracellular level of glutamate, is maintained within narrow limits. A proposed
      index for excitatory neurodegeneration, glutamate x glycine/GABA, was found to be
      decreased in this seizure model. We therefore suggest that seizure-induced neuron
      death is not reflected by alterations in the extracellular levels of glutamate
      and aspartate, thought to act as direct neurotoxins.

PMID- 1362316
TI  - The 6th Sandbjerg Symposium. Dementia Research in Denmark. The Danish Society of
      Neurosciences. May 1992. Abstracts.

PMID- 1362315
TI  - Glutamate and aspartate are decreased in the skin in amyotrophic lateral
      sclerosis.
AB  - We measured the levels of amino acids in biopsied skin from eight patients with
      amyotrophic lateral sclerosis (ALS) and seven controls. The most conspicuous
      changes in ALS patients were as follows. First, the contents of the acidic amino
      acids glutamate and aspartate were significantly decreased in ALS, and were
      negatively and significantly associated with the duration of illness. Second, the
      levels of the collagen-associated amino acids hydroxyproline, proline, glycine,
      alanine, and hydroxylysine were significantly decreased in ALS, and correlated
      inversely with the duration of illness. These results suggest that there are
      abnormalities of acidic amino acids and collagen-associated amino acids in the
      skin of patients with ALS. These changes may underlie the pathogenesis of ALS.

PMID- 1362317
TI  - [Amphetamine--induced rage reaction in mice and its mechanism].
AB  - Rage reaction was induced in mice by ip amphetamine sulfate (APT) 15 mg/kg. Mice
      appeared hyperreactive after 6 min and then squeaked and fought each other. These
      manifestations were most distinct in 15-30 min and subsided after 40-70 min. At
      20 degrees C and 25 degrees C, the occurrence of rage reaction was 85.0% and
      90.0% respectively. The ED50 of APT for eliciting rage reaction was 11.8 +/- 2.1
      mg/kg ip. No significant difference in the induction of rage reaction was
      observed between male and female mice but ambient temperature affected the
      occurrence of this reaction. Neuroleptic drugs (chlorpromazine, haloperidol,
      tardan and clozapine), anxiolytic drugs (diazepam and meprobamate) and reserpine
      suppressed the rage reaction induced by APT in mice. Phenobarbital and
      pentobarbital (at sedative doses), atropine, scopolamine, phentolamine and
      propranolol exerted no influence on APT--induced rage reaction. Amantadine,
      levodopa and apomorphine at lower doses potentiated the rage inducing effect of
      APT. Moreover, at higher doses amantadine or levodopa alone also evoked rage
      reaction similar to that induced by APT. Therefore, it may be deduced that the
      APT-induced rage reaction results from increased release of dopamine in limbic
      system and has nothing to do with the simultaneous epinephrine release. The
      available data indicate that the APT--induced rage reaction in mice deserves to
      be recommended as an animal model for screening potential neuroleptic drugs. The
      merits and shortcomings of this new model are discussed.

PMID- 1362318
TI  - Vagally mediated release of gastrin and cholecystokinin following sensory
      stimulation.
AB  - The aim of the present study was to investigate whether gastrin, cholecystokinin
      (CCK) and somatostatin secretion can be influenced by sensory stimulation and if
      so, whether such effects are mediated via the vagal nerves. Male rats
      anaesthetized with chloral hydrate were exposed to three different stimuli, i.e.
      to low frequency (2 Hz) electrical stimulation of muscles via needles (electro
      acupuncture), to thermal stimulation at 40 degrees C or to vibration at 100 Hz.
      The two former stimuli activate mainly small and medium sized myelinated fibres
      from muscles and skin respectively, whereas vibration activates large myelinated
      fibres from skin, subcutaneous tissue and muscles. Experiments were also
      performed on animals that were vagotomized or exposed to prior treatment with
      atropine (0.5 mg kg-1). Blood was collected at various time intervals and plasma
      levels of gastrin, CCK and somatostatin were measured with radioimmunoassay
      (RIA). All three stimuli, i.e. electro-acupuncture, vibration and thermal
      stimulation caused significant elevations of gastrin (103 +/- 11-151 +/- 16 pM,
      105 +/- 8-140 +/- 12 pM and 105 +/- 14-162 +/- 4 pM) and cholecystokinin (9 +/-
      0.8-15 +/- 2.8 pM, 8 +/- 0.5-10 +/- 1.5 pM and 8.0 +/- 0.5-10.5 +/- 1.5).
      Somatostatin was raised in response to electro-acupuncture (10 +/- 1-14 +/- 3
      pM). Vagotomy and atropinization abolished the release of gastrin and CCK in
      response to all three stimuli. CCK levels were significantly reduced following
      electro-acupuncture in atropinized rats. In conclusion, gastrin and
      cholecystokinin release is stimulated by activation of sensory afferent,
      originating in skin, subcutaneous tissue as well as in muscle.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1362319
TI  - Intracranial haemodynamics in Takayasu's arteritis.
AB  - The cerebral circulation was assessed in two cases of Takayasu's arteritis by
      angiography of the aortic arch, cerebral blood flow single photon emission
      computed tomography (SPECT) and transcranial Doppler sonography (TCD). In both
      cases, disease of the major brachiocephalic arteries affected flow in the
      vertebrobasilar system and circle of Willis. Basilar artery flow was permanently
      reversed in one case, with vertebrovertebral shunting and subclavian steal. In
      the other case, focally reduced cerebral hemisphere flow resulted from watershed
      between vascular territories. The complex collateral and haemodynamic changes
      produced by multi-vessel involvement in Takayasu's arteritis suggest that
      therapeutic approaches should be based on assessment of end-organ perfusion
      rather than on structural angiographic changes.

PMID- 1362321
TI  - Southern blot hybridization analysis of polyoma virus-specific RNA synthesized
      under the block of virus replication by 5-bromo-2'-deoxyuridine.
AB  - Polyoma (Py) virus-specific RNA, synthesized at reduced level in infected cells
      in the presence of antiviral substance 5-bromo-2'-deoxyuridine was characterized
      in more detail by Southern blot hybridization analysis. Virus-specific RNA
      present in 3H-uridine labelled cytoplasmic preparations hybridized to individual
      viral DNA restriction fragments in a characteristic manner and extent, which was
      quantitatively assayed. BrdUrd (6.34 micrograms/ml) lowers the hybridization
      profiles essentially in a proportional manner, which indicates that no new,
      atypical transcription products are formed in the presence of BrdUrd.

PMID- 1362320
TI  - Hepatitis B vaccine alone or in combination with anti-HBs immunoglobulin in the
      perinatal prophylaxis of babies born to HBsAg carrier mothers.
AB  - The efficacy of hepatitis B virus (HBV) vaccine alone (group I) or in combination
      with hepatitis B immunoglobulin (HBIG) (group II) for prevention of perinatal
      transmission of the virus was assessed in 21 and 24 neonates, respectively. 58
      infants who could not be vaccinated constituted the control group. It was
      observed that in the unvaccinated group approximately 70% of the infants became
      infected. In both the vaccinated groups, the seroconversion and seroprotection
      rates (anti-HBs > or = 10 IU/1) were almost similar at 6 months of follow up,
      but, at 12 months, infants given HBIG and vaccine showed better seroprotection
      rate (85%) than those given vaccine alone (58.8%). Immune response to the vaccine
      was also better in both the groups if the mothers were anti-HBe positive. Despite
      immunization, 14.2% and 25% infants in group I and II, respectively, became
      chronic carriers if their mothers were HBeAG positive.

PMID- 1362322
TI  - Induction of interferon synthesis and cytotoxicity by murine peritoneal
      macrophages exposed to glycoprotein ligands.
AB  - Thioglycollate-induced murine C57BL/6 and C3H/HeN peritoneal macrophages
      synthesized interferon-beta (IFN-beta) in response to exposure to glycoproteins
      such as horseradish peroxidase (HRP) or mannosyl or fucosyl bovine serum albumin
      (BSAman of BSAfuc, respectively), but not glucosylated or galactosylated BSA
      (BSAglu or BSAgal, respectively). These results suggest participation of the
      mannosyl-fucosyl receptor (MFR) in this response. IFN synthesis was augmented by
      culturing macrophages in L cell-conditioned medium prior to exposure to these
      substances. Macrophages obtained from lipopolysaccharide (LPS)-resistant C3H/HeJ
      mice did not produce IFN in response to HRP. Furthermore, IFN-induction by HRP
      was blocked by polymyxin B. In addition, exposure of macrophages to HRP or BSAman
      induced cytotoxicity against NIH 3T12 cells. Cytotoxicity was not inhibited by
      the presence of anti-IFN-alpha/beta. In contrast to IFN induction, however,
      macrophages activation was LPS-independent, since this activity was demonstrated
      in macrophages from C3H/Hej mice. The carbohydrate specificity of these responses
      suggests that the MFR or an another scavenger receptor may be involved in the
      responses to these substances, and that cytotoxicity and IFN-induction by
      glycoproteins follow unique pathways.

PMID- 1362324
TI  - Monoclonal antibody to Japanese encephalitis virus cross-reacting with histones
      present in the cell nuclei.
AB  - An immunoglobulin G (IgG2b) class of monoclonal antibody (MoAb, NHA-1) raised
      against Japanese encephalitis virus (JEV) E glycoprotein, reacted with the viral
      antigen expressed in cytoplasm of the infected cells and also with the cell
      nuclei, by an indirect fluorescent antibody technique (FA). The NHA-1 reactivity
      to nuclei was found to be due to its recognizing a JEV cross-reactive epitope
      present on the nuclear histones. Adsorption with calf thymus histones (type II
      AS) showed a drop in NHA-1 reactivity to both JEV and histones by an enzyme
      linked immunosorbent assay (ELISA) and indirect FA; the drop was higher against
      the histones. The MoAb recognized specifically the viral antigens expressed on
      the infected porcine kidney cell surface by a modified indirect FA. ELISA carried
      out with glutaraldehyde-fixed antigens showed an almost 2-fold increase in the
      reactivity over unfixed JEV antigen but none for the histones. Thus, the results
      indicate that histones share a sequential homology with E glycoprotein of JEV,
      which might lead to an autoimmune disorder induced due to the molecular mimicry
      between these two antigens.

PMID- 1362323
TI  - Prevalence and specificity of lymphocytotoxic antibodies in different stages of
      HIV infection.
AB  - Sera obtained from 27 HIV-infected persons were investigated for complement
      dependent humoral cytotoxicity. Uninfected as well as HTLV-IIIB-infected H9 cells
      were used as cellular targets either before or after stimulation by
      phytohemagglutinin (PHA) or concanavalin A (Con-A). The degree of cytotoxicity
      was determined by 51Cr-release assay. Two different antibodies could be found in
      sera of HIV-infected persons, one being directed against HIV-induced cell surface
      component(s) and the other reacting with structure(s) present on activated T4
      cells. Asymptomatic HIV-carries were found to have antibodies exerting complement
      dependent cytotoxicity to HIV-infected T4 cells. These antibodies were reactive
      mainly after stimulation of HIV-infected target cells by Con-A. Sera of ARC and
      AIDS patients contained autoantibodies reactive with PHA-stimulated or HIV
      infected T4 lymphocytes. These data suggest that HIV-specific antibodies
      represent an anti-viral immune defense, while autoantibodies may be important in
      destruction of the immune system in AIDS.

PMID- 1362325
TI  - Experimental studies on the susceptibility of Aedes vittatus to dengue viruses.
AB  - Ae. vittatus mosquitoes were infected by oral route and by intrathoracic
      inoculation with dengue (DEN) viruses and tested for the presence of dengue virus
      antigen in their head squashes and salivary glands by indirect
      immunofluorescence. The results indicate that this species was susceptible to all
      four types of DEN viruses and supported the growth of DEN-2 virus.

PMID- 1362326
TI  - Prenatal exclusion of choroideremia.
AB  - We performed prenatal testing to predict the inheritance of choroideremia (CHM)
      using a linked polymorphic DNA marker, DXS95. DNA analysis of chorionic villi at
      the 12th week of pregnancy indicated that the allele at risk had not been passed
      from the heterozygous mother to the fetus. This prenatal exclusion of
      choroideremia was confirmed by polymerase chain reaction-single-strand
      conformation polymorphism (PCR-SSCP) analysis.

PMID- 1362327
TI  - Renal dopamine receptors and pre- and post-cAMP-mediated Na+ transport defect in
      spontaneously hypertensive rats.
AB  - We have reported defective coupling of the renal tubular DA1 dopamine receptor to
      adenylyl cyclase in both the spontaneously hypertensive rat (SHR) and the Dahl
      salt-sensitive rat. Since Na+, 5'-guanyl imidodiphosphate [Gpp(NH)p], and N
      ethylmaleimide (NEM) reduce agonist affinity for brain D1 dopamine receptors, we
      compared the effects of these agents on agonist affinity in proximal tubules from
      SHR and its normotensive control, the Wistar-Kyoto rat (WKY), to delineate
      further the site of the DA1-adenylyl cyclase coupling defect. In WKY, the D1/DA1
      agonist, fenoldopam, competed for 125I-Sch 23982 at a high-affinity site (KiH =
      1.8 +/- 0.8 x 10(-8) M) and a low-affinity site (KiL = 7.6 +/- 1.1 x 10(-5) M, n
      = 6). Na+ (150 mM) or Gpp(NH)p (10(-4) M) converted KiH to KiL. NEM, which
      alkylates sulfhydryl groups, also converted all the binding to KiL; this effect
      could be prevented by prior treatment with 10(-4) M fenoldopam. In contrast, in
      SHR, fenoldopam detected only a KiL (7.8 +/- 1.4 x 10(-5) M, n = 6). Neither Na+,
      Gpp(NH)p, nor NEM had any effect on KiL. To study a functional expression of
      these binding sites, the effect of 5 x 10(-5) M fenoldopam or 8
      (chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (8-CPT-cAMP) on Na+/H+
      exchange activity in proximal tubular brush-border membrane vesicles was tested.
      In WKY, the inhibitory effects of these agents on the exchanger increased with
      the age of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362328
TI  - Hormone signaling systems in inner medullary collecting ducts.
AB  - The inner medullary collecting duct is a complex tissue that exhibits a variety
      of hormone signaling systems. These include the following: adenylyl cyclase
      activity stimulated by vasopressin (AVP), beta-adrenergic agonists, or
      prostanoids and inhibited by alpha 2-adrenergic agents or adenosine; guanylate
      cyclase activity in response to atrial natriuretic peptide (ANP); phospholipase C
      activity stimulated by ANP, AVP, bradykinin, endothelin, epidermal growth factor
      (EGF), and muscarinic cholinergic agents; and phospholipase A2 activity
      stimulated by AVP, bradykinin, EGF, and endothelin. The signal transduction
      mechanisms for each of these hormone signaling systems is succinctly reviewed,
      and the interactions between different signaling pathways are discussed. Central
      to this interaction is the mutually inhibitory relationship between activation of
      adenylyl cyclase and phospholipases. Increasing cellular adenosine 3',5'-cyclic
      monophosphate content impairs activation of phospholipases A2 and C; conversely,
      stimulation of phospholipase C impairs AVP-stimulated adenylyl cyclase activity
      via activation of protein kinase C.

PMID- 1362329
TI  - Phalloidin prevents leukocyte emigration induced by proinflammatory stimuli in
      rat mesentery.
AB  - The objective of this study was to determine whether phalloidin, a potent
      microfilament stabilizer, can modify inflammatory mediator-induced leukocyte
      adhesion and extravasation in postcapillary venules of the rat mesentery. To
      address this issue, the rat mesentery was prepared for in vivo microscopic
      observation. Venules with initial diameters ranging between 25 and 35 microns
      were selected for study. Erythrocyte velocity, vessel diameter, leukocyte rolling
      velocity, and the number of adherent (stationary for 30 s) and emigrated
      leukocytes were initially determined during superfusion of the mesentery with
      phosphate-buffered saline. After these variables were recorded during the control
      period, either 100 nM platelet-activating factor (PAF), 20 nM leukotriene B4
      (LTB4), or 1 microM N-formyl-methionyl-leucyl-phenylalanine (FMLP) was added to
      the superfusate. Repeat measurements were obtained between 50 and 60 min after
      initial exposure to the inflammatory mediator. In some experiments, rats were
      given phalloidin (25 or 500 micrograms/kg iv) 30 min before superfusion with the
      inflammatory mediators. Superfusion of the mesentery with either PAF, LTB4, or
      FMLP enhanced leukocyte adherence and emigration and reduced leukocyte rolling
      velocity. Pretreatment with the low dose of phalloidin effectively prevented
      leukocyte emigration but had no effect on the increased leukocyte adherence
      elicited by the three inflammatory mediators. However, when administered at the
      higher dose, phalloidin prevented both leukocyte adherence and emigration.
      Neither dose of phalloidin altered the upregulation of neutrophil membrane
      CD11/CD18 glycoprotein adherence complex induced by PAF or LTB4. These results
      are consistent with the concept that PAF, LTB4, and FMLP increase leukocyte
      extravasation by a process that may involve alterations in the endothelial cell
      cytoskeleton.

PMID- 1362330
TI  - Alpha-adrenergic vasoconstriction in normal and hypoperfused myocardium during
      sympathetic nerve stimulation.
AB  - Coronary vasoconstriction mediated by postjunctional alpha 1- and alpha 2
      adrenergic receptors was studied in normally perfused (control group) and left
      coronary hypoperfused (stenosis group) hearts of vagotomized, beta-blocked
      (propranolol) cats. Cardiac sympathetic nerve stimulation was combined with alpha
      1- and subsequent alpha 2-adrenergic antagonism (doxazosin and SK&F 104078).
      Coronary perfusion pressure and heart rate were kept constant within groups;
      regional myocardial blood flow and cardiac output were obtained by means of
      microspheres with concomitant measurement of left ventricular myocardial oxygen
      consumption (MVO2). alpha 1-Adrenergic antagonism alone did not significantly
      alter blood flow in any wall layer in either group. Subsequent alpha 2-adrenergic
      antagonism increased epicardial as well as composite transmural flow in the
      stenosis group (P < 0.025). The inverse correlation between coronary resistance
      and MVO2 vanished in the stenosis group following alpha 1- and alpha 2-adrenergic
      antagonism. Maximal first derivative of the left ventricular pressure-time
      relation (dP/dt) and cardiac output were reduced simultaneously (P < 0.001).
      Hence, the significance of alpha 1- and alpha 2-adrenergic stimulation of
      inotropy and cardiac performance are augmented by myocardial hypoperfusion.
      Furthermore, alpha 2-adrenergic receptors are responsible for epicardial
      vasoconstriction in hypoperfused myocardium.

PMID- 1362331
TI  - Effect of afterload and beta-adrenergic blockade on nonischemic myocardial
      contraction pattern.
AB  - We studied how changes in afterload affect regional contraction in the anterior
      wall of the left ventricular after circumflex coronary arterial (CFX) occlusion
      and subsequent beta-adrenergic blockade in pentobarbital sodium-anesthetized
      cats. Regional function was determined by orthogonal sonomicrometry. CFX
      occlusion produced nonuniform hyperkinesis in the nonischemic anterior wall;
      shortening of circumferential segments increased from 10.1 to 14.1% (P < 0.001),
      whereas shortening of longitudinal segments increased from 3.0 to 9.6% (P <
      0.001). Hyperkinesis of longitudinal segments was influenced neither by changes
      in afterload over a pressure range of +/- 30 mmHg nor by beta-adrenergic
      blockade, indicating that hyperkinesis of longitudinal segments does not rely on
      increased inotropic state or resistance to ventricular emptying. Hyperkinesis of
      longitudinal segments occurred at end-diastolic lengths equal to preocclusion
      conditions, whereas hyperkinesis of circumferential segments was dependent on
      activation of the Frank-Starling mechanism. Furthermore, shortening of
      circumferential segments decreased with increments in afterload, particularly
      after CFX occlusion and subsequent beta-adrenergic blockade. In conclusion, CFX
      occlusion alters the contraction pattern of the nonischemic anterior wall. The
      postocclusion contraction is sensitive to increased afterload in the cardiac
      minor axis direction. These initial alterations may well direct the following
      remodeling process in infarcted hearts.

PMID- 1362333
TI  - Desensitization to acetylcholine in single sinoatrial node cells isolated from
      rabbit hearts.
AB  - The negative chronotropic effect of acetylcholine (ACh) on the sinoatrial node
      fades in the continuous presence of ACh as a result of desensitization. We have
      investigated the mechanism underlying desensitization in single rabbit sinoatrial
      node cells using the whole cell patch clamp technique. The negative chronotropic
      effect resulting from the injection of a constant hyperpolarizing current faded.
      ACh activated an inwardly rectifying potassium current (iK,ACh), which faded in
      the continuous presence of ACh. ACh had no effect on "basal" L-type calcium
      current (iCa), but ACh decreased iCa, which had been potentiated by isoprenaline.
      This effect did not fade during a 2-min exposure to ACh. ACh decreased the
      hyperpolarization-activated current (i(f)). This effect again did not fade. These
      results suggest that desensitization of the negative chronotropic response to ACh
      is, in part, the result of the membrane hyperpolarization and, in part, the
      result of the fade of iK,ACh. These results also suggest that, whereas the
      activation of potassium current by ACh rapidly fades, the effects resulting from
      the inhibition of adenylate cyclase do not.

PMID- 1362332
TI  - Baroreflex control of regional capacitance and blood flow distribution with or
      without alpha-adrenergic blockade.
AB  - Regional blood volumes (Vb), unstressed volumes (V0), blood flow distribution,
      venous compliances (Cv), venous resistances (Rv), and time constants of drainage
      (tau v) were determined in dogs anesthetized with alpha-chloralose at carotid
      sinus pressures (Pcs) of 50 and 200 mmHg and dosed with alpha-adrenergic or
      ganglionic blockade at a Pcs of 50 mmHg. Vb was measured in each region from
      indicator dilution curves and mean transit times. V0 was extrapolated from the
      pressure-volume curves. Pcs of 50 and 200 mmHg were maintained in random order.
      With a decrease in Pcs, arterial pressure increased from 58.7 +/- 4.1 to 104.6 +/
      6.4 mmHg (P < 0.01), peripheral fractional blood flow decreased from 69.8 +/-
      3.8 to 55.8 +/- 3.9% (P < 0.001), splanchnic Vb decreased from 28.3 +/- 1.9 to
      19.3 +/- 1.2 ml/kg (P < 0.01), and splanchnic V0 decreased from 19.6 +/- 1.4 to
      6.3 +/- 2.1 ml/kg (P < 0.001). Splanchnic Rv and tau v also decreased, whereas
      splanchnic Cv increased. Phentolamine at low Pcs only partially reversed the
      decrease in splanchnic capacitance, whereas hexamethonium completely abolished
      it. In conclusion, changes in splanchnic Rv and blood flow distribution are
      important components of the carotid sinus reflex, and alpha-adrenergic receptor
      activation is only partially responsible for the changes in vascular capacitance
      by the baroreceptor reflex.

PMID- 1362334
TI  - Alpha 2-adrenoceptors mediate norepinephrine constriction of porcine pial veins.
AB  - The adrenergic innervation and alpha-adrenoceptor agonist-induced constrictions
      in isolated medium-size pial veins (OD 734 +/- 18 microns) of the pig were
      investigated. Using in vitro tissue bath techniques, we noted exogenously applied
      norepinephrine (10(-9) to 10(-5) M) induced venoconstriction with EC50 values of
      1.71 x 10(-7) M, where EC50 is the concentration that produced 50% of (non-KCl)
      agonist-induced maximum constriction. The constriction was mimicked by clonidine
      but not by phenylephrine and was more effectively blocked by yohimbine than by
      prazosin. Results from histochemical studies demonstrated that porcine pial veins
      received a denser plexus of catecholamine fluorescence fibers than do pial
      arteries with similar outer diameter. These results suggest that norepinephrine
      induced pial venoconstriction is mediated predominantly by alpha 2-adrenoceptors
      and that porcine pial veins have significantly greater sensitivity to the alpha
      action of norepinephrine than that reported in pial arteries. These results add
      further support for adrenergic innervation in pial veins being of importance in
      regulating cerebral blood volume and intracranial pressure.

PMID- 1362335
TI  - Age-related decline in left ventricular filling at rest and exercise.
AB  - To determine whether the age-associated decline in resting left ventricular
      diastolic filling persists during aerobic exercise, rest and bicycle exercise
      filling indexes were measured from gated radionuclide blood pool scans in 88
      healthy men aged 22-82 yr. To evaluate the effect of physical conditioning status
      on these age-related changes, a subset of the subjects consisted of endurance
      trained senior athletes with a maximal O2 consumption of 50.5 +/- 5 compared with
      32.6 +/- 7 ml.kg-1 x min-1 in age-matched controls. The contribution of beta
      adrenergic stimulation to exercise-induced changes in filling was also evaluated
      by the administration of intravenous propranolol to another subset before
      testing. Peak filling rate increased progressively at all ages with increasing
      exercise work loads. The peak filling rates at rest, 50% maximal exercise, and
      maximum exercise inversely correlated with age (r = -0.64, -0.53, -0.64,
      respectively). Rest and exercise filling indexes in senior athletes were similar
      to those of sedentary older subjects. Propranolol decreased exercise peak filling
      rates in young (37.2 +/- 7.5 yr) but not in older (62.1 +/- 6 yr) subjects.
      Therefore, filling rates increase with exercise in both young and older healthy
      men, but age differences persist at comparable relative work loads. This decline
      is not secondary to a decline in physical conditioning status but appears to be
      related to a decrease in beta-adrenergic responsiveness in older individuals.

PMID- 1362336
TI  - Proceedings of the 23rd Conference of the International Society for Animal
      Genetics. Interlaken, Switzerland, 3-7 August 1992. Abstracts.

PMID- 1362337
TI  - [Undescended testicle treated with FSH and HCG].
AB  - Medical treatment with FSH and HCG was tested during 21 days in 47 cases (76
      testis) of undescended testis. The average testis size, as measured by ecography,
      increased from 0.828 cc to 1.57 cc 48 hours after completing the treatment. Three
      months later the average testis size was 1.025 cc and 1.24 cc at six months. FSH
      increased slightly and total testosterone and free testosterone increased
      significantly. After treatment, 68% of the previously undescended testis
      descended.

PMID- 1362338
TI  - [Non-Hodgkin's malignant lymphoma and human immunodeficiency virus. Apropos of 34
      cases].
AB  - The characteristics of 34 HIV-associated non Hodgkin's lymphomas diagnosed and
      treated at Bordeaux hospitals are described. The patients represented 7% of the
      AIDS cases observed in the Bordeaux area. HIV-lymphomas were almost always high
      grade malignancies, usually disseminated (70%) with extranodal disease at
      presentation (91%) primarily in the bone marrow, meninges, gastrointestinal tract
      and liver. Twenty-eight patients were treated with different chemotherapy
      protocols or radiation therapy alone. Complete remission was achieved in 11
      patients and partial remission in 3. The median survival was 3.9 months. Despite
      utilization of low-intensity chemotherapy regimens, opportunistic infections were
      not prevented. The only factor that accurately predicted complete remission was
      the WHO performance index. The total number of CD4-positive lymphocytes, the Ann
      Arbor stage and the WHO performance index were prognostic factors influencing
      survival. These results justify the use of high-intensity regimens, but only for
      patients without opportunistic infection and with a WHO performance index below
      3.

PMID- 1362340
TI  - Aging and Cellular Defense Mechanisms. Modena, Italy, September 22-26, 1991.

PMID- 1362339
TI  - [Esophageal candidiasis in HIV positive patients. Lack of statistical correlation
      with CD4 lymphocytes].
AB  - One hundred and twenty-nine upper gastrointestinal endoscopies were performed
      between November, 1986, and November, 1990, at the Fort-de-France Hospital
      (Martinique), on 92 patients who were seropositive for the human immunodeficiency
      virus (HIV). Blood samples were drawn at the same time as 75 endoscopic
      examinations and the number of CD4 lymphocytes/mm3 was determined. The incidence
      of esophageal candidiasis was 23.1% and lesions were observed in 17.2% of the
      endoscopies performed systematically at the time that the patient's
      seropositivity was first established. No significant relationship was found
      between the presence of esophageal candidiasis and peripheral blood CD4
      lymphocyte counts.

PMID- 1362341
TI  - Protein oxidation in aging brain.

PMID- 1362342
TI  - Aged human T cells. Suppressed mitogenic response to activation via CD2 and CD3
      receptors.

PMID- 1362344
TI  - [Is there any desensitization of presynaptic alpha 2-adrenergic receptors in
      hypertension? Experimental and clinical studies].
AB  - Several authors have discussed an alteration of adrenergic receptivity in
      arterial hypertension. De Champlain (Hypertension 1990; 8: S77-S85) suggested
      that postsynaptic alpha 1-adrenergic functions became dominant while beta
      adrenergic functions are attenuated in arterial hypertension. However, the status
      of presynaptic alpha 2-adrenoceptors remains unknown. The present study
      investigates presynaptic alpha 2-adrenoceptors in hypertension through the
      measurement of plasma levels of noradrenaline after administration of yohimbine,
      an alpha 2-adrenoceptor antagonist, in essential hypertension. Yohimbine (0.2
      mg/kg per os) induced a 73% increase of plasma levels of noradrenaline in
      hypertensive patients (n = 12) and a 178% one in normotensive subjects (n = 6, p
      < 0.05). A similar significant difference was found in experimental neurogenic
      hypertension observed in awake dogs 3 weeks after sinoaortic denervation: the
      increase in plasma concentrations of noradrenaline after yohimbine (0.5 mg/kg
      i.v.) was +279% in hypertensive versus +642% in normotensive dogs (p < 0.05). The
      results show that the magnitude of the yohimbine-induced sympathetic activation
      is lower in hypertensives than in normotensives. They suggest the existence of a
      presynaptic alpha 2-adrenoceptor desensitization in arterial hypertension. The
      abnormality of this presynaptic inhibitory mechanism can increase the sympathetic
      tone and help to develop and maintain arterial hypertension.

PMID- 1362343
TI  - Survey of the methicillin resistance-associated genes mecA, mecR1-mecI, and femA
      femB in clinical isolates of methicillin-resistant Staphylococcus aureus.
AB  - The restriction site polymorphism of the chromosomal femAB region and the first
      appearance of the regulatory element mecR1-mecI associated with the methicillin
      resistance determinant (mec) were analyzed in 192 initially methicillin resistant
      (Mcr) Staphylococcus aureus clinical isolates collected between 1965 and 1990 in
      the Zurich area. Forty-three of the strains lost the resistance spontaneously.
      All isolates that were still Mcr hybridized with mecA, the gene for the low
      affinity penicillin-binding protein PBP 2'. Mcr strains isolated before 1977
      lacked sequences that hybridized with mecR1-mecI, a regulatory element
      controlling the expression of mecA; exceptions to this were one strain isolated
      in 1966 and one strain isolated in 1972. The size of the EcoRV fragment carrying
      femA, a chromosomally encoded factor involved in pentaglycine side chain
      formation of the peptidoglycan and essential for the expression of methicillin
      resistance, was conserved in all strains but one, which was susceptible to
      methicillin even though it carried a functional mecA gene. The methicillin
      susceptibility of this particular strain was presumably due to a spontaneous femA
      like mutation. The 192 strains belonged to seven different EcoRV restriction
      fragment patterns recognizable with a 10.5-kb probe covering the femAB region.
      Some 93% of the 149 Mcr strains belonged to pattern A, and the remaining Mcr
      strains shared patterns A' and B. The 42 isolates which spontaneously lost their
      resistance upon storage and revival represented all seven different patterns.
      This strong conservation of femA suggests an important role for femA in cell wall
      metabolism and methicillin resistance.

PMID- 1362345
TI  - [Creatine phosphokinase in a hospitalized psychiatric population].
AB  - Creatine phosphokinase (CPK) is studied in psychiatric hospitalized patients
      under neuroleptic treatment in order to clarify the diagnostic value of this
      enzyme in the neuroleptic malignant syndrome (SNM). Intramuscular drug
      administration was, in the present study, the only variable associated with CPK
      levels over 1,000 U. Other items studied, like agitation, physical restraint or
      illness severity can not account for this elevation. In absence of i.m.
      medication, levels over 1,000 U must be carefully screened in order to rule out
      SNM or organic pathology associated.

PMID- 1362346
TI  - [Soluble intercellular adhesion molecule-I levels in sera of patients with
      Kawasaki disease].
AB  - We investigated whether serum levels of soluble ICAM-1 antigens increases during
      acute Kawasaki disease (KD). We also compared levels in acute KD with those in
      anaphylactoid purpura (AP) and in measles. Serum soluble ICAM-1 levels were
      measured by a double determinant immunoassay using two monoclonal antibodies in
      the FAST system. Serum levels of tumor necrosis factor-alpha (TNF-alpha) were
      measured by a specific and sensitive sandwich enzyme immunoassay. Patients with
      KD, but not with AP or measles, had increased ICAM-1 levels in serum during the
      acute stage. In addition, during the acute stage, KD patients with coronary
      artery lesions (CAL) were found to have increased ICAM-1 levels in serum compared
      to patients without CAL. We found a positive correlation between serum levels of
      ICAM-1 and levels of TNF-alpha during acute KD. Our results suggest that the
      serum level of soluble ICAM-1 is an important immunologic parameter for
      determining the severity of vascular damage during acute KD.

PMID- 1362347
TI  - The expression of presynaptic t-ACPD receptor in rat cerebellum.
AB  - The expression of a receptor subtype for one type of excitatory amino acid
      agonist, t-ACPD, was examined in developing Purkinje cells of cerebellar slices.
      The t-ACPD-induced responses were compared with those induced by QA in current
      response, single cell Ca2+ imaging and changes in the miniature currents in the
      same preparation. It was found that t-ACPD induced a single component of inward
      current, and an increase in the frequency of miniature currents associated with
      the presence of external Ca2+, but was ineffective at mobilizing intracellular
      Ca2+ even in the presence of external Ca2+. The present study suggests the
      expression of at least two types of metabotropic receptors in the Purkinje cell
      region, one of which, expressed in the Purkinje cell dendrites, is highly
      sensitive to QA, but relatively insensitive to t-ACPD, and the other of which is
      a t-ACPD-sensitive receptor expressed on the presynaptic terminals of the neurons
      making synapses onto Purkinje cells.

PMID- 1362348
TI  - Molecular characterization of the gene encoding glutamine synthetase in the
      cyanobacterium Calothrix sp. PCC 7601.
AB  - In order to study the regulation of the synthesis of glutamine synthetase in
      response to changes in environmental parameters (light and nitrogen sources), we
      have cloned and sequenced the glnA gene from the filamentous cyanobacterium
      Calothrix PCC 7601. This gene consists of 472 codons and encodes a polypeptide of
      M(r) 52,290 highly homologous to that from Anabaena PCC 7120, but more distant
      from those identified from other procaryotes. The relative abundance of the two
      glnA transcripts (1.6 and 1.8 kb) is equivalent in cells grown under either red
      or green light, but the 1.6-kb species predominates in nitrate-grown cells and
      the 1.8-kb species in ammonia-grown cells. The very high identity (74%) observed
      between the 374-bp long nucleotide sequence upstream from the Calothrix and
      Anabaena glnA genes suggests the existence of similar regulatory signals for the
      control of glnA expression in both cyanobacteria.

PMID- 1362349
TI  - Evidence of tyrosine hydroxylase mRNA in the anterior and neurointermediate lobes
      of female rat pituitary.
AB  - The anterior pituitary is thought to be unable to synthesize dopamine (DA) except
      under experimental conditions where a tyrosine hydroxylase (TH) activity, the
      rate-limiting step of its synthesis, has been demonstrated. In this work, we
      tested whether the enzyme described as active under particular conditions comes
      from de novo TH gene transcription or from a pre-existing TH mRNA poorly
      translated or untranslated under physiological conditions. Therefore, we searched
      for the presence of TH mRNA in normal female rat pituitary using the polymerase
      chain reaction following reverse transcription (RT/PCR) and in situ hybridization
      (ISH). The neurointermediate lobe (NIL) of the hypophysis was used as negative
      tissue, since it is thought to be unable to synthesize TH. As expected, no ISH
      labelling could be seen in the neural lobe (NL). However, scarce labelled cells
      were found in the intermediate lobe (IL) confirming the positive results observed
      in the NIL by RT/PCR. The anterior lobe (AL) also presented TH mRNA by PCR and
      ISH. The TH gene expression in sparse cells of the AL is discussed in regard to
      the ability of the AL to synthesize DA under particular conditions from a pre
      existing mRNA.

PMID- 1362350
TI  - Uptake of broxaterol by cultured human cells.
AB  - The mechanism of uptake of the sympathomimetic drug broxaterol by Chang liver and
      HepG2 cell lines was investigated. When cells were incubated in the presence of
      low concentrations of broxaterol cell cultures take up (t1/2 = 5-10 min) and,
      depending on the experimental conditions, accumulate the drug such that the
      intracellular concentration is over 200-1000 times that in the incubation medium.
      The uptake was saturable and influenced by the presence of sodium and variations
      in external pH. These data may represent a model for tissue uptake in vivo in an
      attempt to investigate that selective uptake of broxaterol is involved in
      withdrawal of the molecule during drug therapy.

PMID- 1362352
TI  - omega-Dialkylaminoalkyl esters of N-phenyl aminethiocarboximidic acids with local
      anesthetic and other activities.
AB  - A series of omega-dialkylaminoalkyl esters of N-phenyl aminethiocarboximidic
      acids was prepared by reaction of N-phenyl 1-pyrrolidine, 1-piperidine, 4
      morpholine, 1,2,3,4-tetrahydro-1-quinoline, 1,2,3,4-tetrahydro-2-isoquinoline, 10
      phenothiazine, N-phenyl-2-pyridylamine and N-benzyl-2-pyridylamine
      carbothioamides (prepared in situ from the appropriate secondary amine and phenyl
      isothiocyanate) with a number of omega-chloroalkyldialkylamines in anhydrous DMF
      or THF solution in the presence of sodium hydride. Good yields of the above
      esters were obtained provided that sodium hydride was added initially or after
      the formation of 3,3-disubstituted 1-phenylthiourea, according to the nature of
      the secondary amine. Some esters showed in mice local anesthetic activity
      comparable with that of lidocaine, as well as moderate hypoglycemic,
      antiarrhythmic, analgesic, antiacetylcholine, H1-antithistamine and platelet
      antiaggregating activities.

PMID- 1362351
TI  - Increase in activating ability of human platelet guanylate cyclase during
      aggregation.
AB  - The dynamics of changes in the stimulation of human platelet guanylate cyclase by
      some activators in aggregating platelets was studied. It was shown that ADP
      induced aggregation of human platelets (donors) is accompanied by the enhancement
      of the intensity of guanylate cyclase activation by sodium nitroprusside, L
      arginine, protoporphyrin IX and arachidonic acid and also by the increase in cGMP
      content. Immediately after the induction of aggregation the intensity of
      guanylate cyclase activation and cGMP content begin to increase. The rise reaches
      its maxima within several minutes, then followed by a fall to the initial level.
      The peaks of the enhanced capacity for guanylate cyclase activation by the above
      compounds coincide in time and intensity. On the basis of the proposed
      hypothetical scheme of cGMP action as a regulator of platelet aggregation a
      possible mechanism of enhancing the capacity of guanylate cyclase to be
      stimulated by various activators in aggregating platelets is suggested.

PMID- 1362353
TI  - 8-Methoxy- and p-dimethoxy-1-aminoethylhetero-tetralins: synthesis and DA, 5-HT
      receptors affinities.
AB  - Two series of compounds, 8-methoxy- and p-dimethoxy derivatives of 1
      aminoethylhetero-tetralins, I, were evaluated for D-2, 5-HT1 and 5-HT2 receptors
      affinity. No significant serotoninergic affinity was observed, whereas p
      dimethoxy-derivatives 7b e 11b showed a moderate D-2 affinity.

PMID- 1362354
TI  - Pharmacological properties of new 1,2-benzisothiazolyloxypropanolamines on
      cardiac and tracheal beta-receptors.
AB  - This paper reports the pharmacological assessment of beta-blocking properties of
      new benzisothiazole and benzisoxazole derivatives, substituted in position 3-, 5-
      or 7- with the oxypropanolaminic side chain (I-VI), to of which contain the -OCH3
      group in position 3- (III, V) in comparison with propranolol. The results,
      obtained on isoprenaline-induced chronotropic response of rat isolated atria and
      on isoprenaline-induced relaxation of guinea-pig tracheal strips precontracted by
      carbachol, suggest that the compounds (I, II, IV, VI), at variance with the
      methoxy-substituted (III, V), possess a beta 1-blocking activity 4-300 times
      lower than propranolol. pA2 values drop from 8.36 to 7.56 and 7.04 from the
      relative compounds substituted in position 7- (IV), 3- (I) and 5- (II), thus
      indicating that the position of the oxypropanolaminic chain in the
      benzisothiazole ring affects the ability of the molecules to interact with the
      beta 1-adrenoceptor. Furthermore, benzisothiazole rather than benzisoxazole ring
      seems to facilitate the drug-beta 1 adrenoceptor interaction, the compound (I)
      displaying a 10-fold higher affinity than compound (VI).

PMID- 1362355
TI  - [HIV-1 proviral DNA sequences in the saliva of patients with HIV infection].
AB  - In order to understand the significance of presence of HIV-1 in saliva, we
      searched for by PCR HIV-1 proviral sequences in the saliva cells of 49 HIV-1
      infected patients. Seven out 49 specimens resulted positive, 4 of which were from
      patients with PGL, 1 with ARC and 2 with AIDS. Four patients had a CD4+
      lymphocyte counts < 200/cmm and in 3 patients the CD4+ lymphocyte count ranged
      from 200 to 400/cmm. Two patients were treated with AZT, 1 with DDI and 4 had no
      antiretroviral treatment. In conclusion, although HIV-1 proviral sequences have
      been found in saliva of HIV-1 infected patients, a larger group of patients
      should be investigated to define more precisely the role of HIV-1 in saliva.

PMID- 1362357
TI  - Down-regulation of protein kinase C potentiates atrial natriuretic peptide
      stimulated cGMP accumulation in vascular smooth-muscle cells.
AB  - It has been reported that atrial natriuretic peptide (ANP) produces inositol
      phosphates and diacylglycerol in vascular smooth muscle cells (VSMC). The purpose
      of this study is to investigate whether diacylglycerol produced by ANP affects
      ANP-induced cyclic GMP (cGMP) accumulation through the activation of protein
      kinase C. Short-term (15 min) treatment of rat aortic VSMC with protein kinase C
      activating phorbol 12-myristate 13-acetate (PMA, 100 nM) decreased ANP (100 nM)
      induced cGMP accumulation by 34.7% in the presence of IBMX (0.5 mM). However, the
      long-term (24 h) treatment to decrease the activity of protein kinase C led to an
      enhancement of the cGMP accumulation by 69.6% compared with that of control VSMC.
      There were no significant differences in Bmax and Kd for ANP and ANP-dependent
      particular guanylyl cyclase activity between long-term PMA-treated and control
      VSMC. In the present study, we show that the activation of protein kinase C
      attenuates the cGMP accumulation induced by ANP and that down-regulation of
      protein kinase C results in an enhancement of the cGMP accumulation. These data
      are consistent with the role of protein kinase C as a negative regulator in ANP
      receptor/guanylyl cyclase pathway.

PMID- 1362358
TI  - 3,5-Dihydroxyphenyl-glycine: a potent agonist of metabotropic glutamate
      receptors.
AB  - An amino acid, 3,5-dihydroxyphenylglycine (DHPG) induced current responses in
      Xenopus oocytes expressing a metabotropic glutamate receptor clone mGluR1.
      Apparent EC50 of DHPG for mGluR1 was slightly lower than that of (+-)-1
      aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD). DHPG responses were
      partially inhibited by 2-amino-3-phosphonopropionic acid (AP-3). DHPG had no
      effect on ionotropic glutamate receptors whose expression was induced in the
      oocytes following injection of poly(A)+ mRNA of rat brains. In hippocampal
      slices, DHPG produced slow excitation of pyramidal cells, resulting from a
      depression of Ca(2+)-dependent K+ current and a voltage-dependent K+ current.
      These results indicate that DHPG is a specific and potent agonist of mGluRs.

PMID- 1362356
TI  - The molecular study of bacterial virulence: a review of current approaches,
      illustrated by the study of adhesion in uropathogenic Escherichia coli.
AB  - Pathogenic bacteria coexist with their hosts in a relationship which most
      frequently allows persistence of the bacteria without causing disease. In a small
      proportion of colonised individuals the complex mutual interaction between
      microbe and host is upset, leading to disease in the host. The investigation of
      bacterial virulence determinants and their genetic control at the molecular level
      is an important facet of the development of strategies to combat disease. This
      review focuses on the investigation of a single pathogenic organism as a means of
      illustrating modern approaches to the investigation of bacterial virulence. The
      importance of uropathogenic Escherichia coli in causing acute and recurrent
      pyelonephritis with the consequent morbidity of chronic renal failure is well
      established. Pyelonephritis-associated (Pap) pili are likely to be critical
      virulence factors in uropathogenic E. coli. The evidence for their role in
      pathogenicity and the control of their expression at the molecular genetic level
      is discussed.

PMID- 1362359
TI  - Nitric oxide mediated formation of cyclic GMP in the olfactory system.
AB  - Olfactory cilia preparation from rats contain considerable activity of soluble
      guanylate cyclase as indicated by the formation of cyclic GMP (cGMP) upon
      application of nitroprusside, a nitric oxide generating agent. Stimulation of
      olfactory cilia with high doses of odorants elicited a delayed and sustained
      elevation of the cGMP-concentration. The odorant-induced cGMP-response was
      abolished by L-NG-nitro-arginine, a selective inhibitor of nitric oxide
      synthesis, as well as by haemoglobin which efficiently binds and inactivates
      nitric oxide. These observations suggest that the NO/cGMP cascade may plan an
      important role in signal processing of the olfactory system.

PMID- 1362361
TI  - Proteinuria and Progressive Renal Disease. 1st International Symposium. Paris,
      July 2, 1992. Abstracts.

PMID- 1362360
TI  - Receptor autoradiography with 11C and [3H]-labelled ligands visualized by imaging
      plates.
AB  - The distribution of histamine H1, H3, dopamine D1 and D2 receptors in the brain
      was studied by receptor autoradiography using a high-sensitivity and high
      resolution imaging plate system. [3H]Pyrilamine, [3H](R)alpha-methyl-histamine,
      [11C]SCH23390, and [11C]N-methylspiperone (or [11C]YM-09151-2) were used as
      ligands to identify H1, H3, D1 and D2 receptors, respectively. Two different
      receptors (dopamine D2 and histamine H3) could be also labelled simultaneously in
      a single cryostat-sliced section using [11C]N-methylspiperone and [3H](R)alpha
      methylhistamine, respectively. The imaging plate system is useful for receptor
      autoradiography of positron emitter-labelled and tritium-labelled receptor
      ligands because of its high sensitivity.

PMID- 1362362
TI  - The use of the guinea-pig lung parenchyma preparation in studies of the beta
      adrenoceptor adenylate cyclase system.
AB  - The binding, adenylate cyclase activation, and functional effect of four beta
      adrenoceptor agonists were studied in the guinea-pig lung parenchyma preparation
      and the results were compared with those obtained earlier in guinea-pig left
      heart ventricle (beta 1-adrenoceptors) and soleus muscle (beta 2-adrenoceptors)
      preparations. The pKi-values of the unselective compounds, isoprenaline and
      orciprenaline, were in good agreement with those obtained in the heart and soleus
      muscle. The beta 2-adrenoceptor selective compounds KWD 2026 and terbutaline were
      bound to two sites, one corresponding to the beta 1-adrenoceptors and the other
      to the beta 2-adrenoceptors. The pKi-value of isoprenaline was in good agreement
      with its pKact-value indicating that maximum adenylate cyclase activity is
      obtained when the occupancy of the receptors is maximal. Further, the relative
      intrinsic efficacy calculated from the functional effect and receptor occupancy
      agreed well with the relative maximum adenylate cyclase activation by the
      agonists which was also found earlier for the guinea-pig heart ventricle and
      soleus muscle preparations. Relative effects were obtained from both functional
      experiments and from affinity and adenylate cyclase activating studies. There was
      good agreement between relative effects obtained in these two ways. It is
      concluded that the guinea-pig lung parenchyma preparation may be useful for the
      study of the beta-adrenoceptor adenylate cyclase system.

PMID- 1362363
TI  - Erythromycin base-induced rash and liver function disturbances.
AB  - OBJECTIVE: To report a case of erythromycin base-induced rash and liver function
      disturbances. CASE SUMMARY: A patient with erythema nodosum and high
      antistreptolysin-O titers was treated with erythromycin on the assumption that
      occult streptococcal infection was the cause of the erythema nodosum. Forty-eight
      hours after the initiation of therapy the patient developed fever, severe
      generalized rash, pruritus, and cholestatic and hepatocellular liver function
      disturbances. Extensive evaluation to determine the cause of liver function
      disturbances was unrevealing. Marked improvement was noticed within days after
      cessation of erythromycin. DISCUSSION: Case reports in the literature on the
      adverse effects of erythromycin and its derivatives were reviewed. The possible
      immunologic mechanism involved is postulated. CONCLUSIONS: Erythromycin base must
      be added to the list of erythromycin derivatives that can cause rash and liver
      function disturbances. The concomitant appearance of fever, rash, jaundice, and
      liver function disturbances raises the possibility of hypersensitivity as the
      mechanism for the liver disturbances.

PMID- 1362364
TI  - Transient hepatic dysfunction in an infant of an epileptic mother treated with
      carbamazepine during pregnancy and breastfeeding.
AB  - OBJECTIVE: A case is reported of a carbamazepine (CBZ)-treated epileptic mother
      whose newborn presented with transient hepatic dysfunction characterized by
      direct hyperbilirubinemia and high concentrations of gamma-glutamyltransferase
      (GGT). DATA SOURCES: Information was obtained from case reports, clinical trials,
      and relevant bibliographic laboratory studies. DATA EXTRACTION: Data from case
      reports were evaluated and compared with those from our patient. The hepatotoxic
      reactions together with the microsomal enzymatic induction of CBZ were reviewed.
      DATA SYNTHESIS: A female infant born to an epileptic mother treated with CBZ
      throughout pregnancy and breastfeeding presented with transient direct
      hyperbilirubinemia and high concentrations of GGT. The characteristics of her
      transient hepatic dysfunction were: early appearance (during the first day of
      life); discrepancy between the normal liver enzymes and high GGT concentrations;
      slow decrease of GGT, which nevertheless remained at above-normal concentrations
      even after the complete disappearance of direct hyperbilirubinemia; and
      spontaneous resolution in spite of only occasional breastfeeding. The possible
      explanations of this transient hepatic dysfunction (like enzymatic induction) are
      discussed. CONCLUSIONS: CBZ-induced hepatic dysfunction in neonates appears to
      have different clinical expressions. Infants of epileptic mothers treated with
      CBZ throughout pregnancy and breastfeeding should be carefully monitored for
      possible adverse effects.

PMID- 1362366
TI  - Myotonic dystrophy: advances in molecular genetics.

PMID- 1362365
TI  - Over-the-counter medications in cardiac transplant recipients: guidelines for
      use.
AB  - OBJECTIVE: The purpose of this article is to review the pathophysiology of the
      denervated heart and the factors that need to be considered before recommending
      the use of over-the-counter (OTC) medications in the cardiac transplant
      recipient. DATA SOURCES: Pharmacology and therapeutic textbooks, English-language
      journal articles, and physiology textbooks published between 1969 and 1991. DATA
      EXTRACTION: Case reports, controlled case studies, and textbook chapters
      evaluating drug interactions with immunosuppressive agents were reviewed. The
      effects of various OTC medications on the denervated heart were examined and
      relevant material was extrapolated. DATA ANALYSIS: The number of cases or studies
      in which a particular effect or interaction occurred was reported. Those findings
      that were less well documented were either identified as such or were not
      included in the review. DATA SYNTHESIS: Common pharmacokinetic and
      pharmacodynamic interactions with the primary immunosuppressive agents (e.g.,
      cyclosporine, azathioprine, prednisone) are reviewed. The physiology and altered
      responses of the denervated heart to various medications are also explained.
      Using this information recommendations are given for the use and monitoring of
      OTC analgesics, antacids, laxatives, sleep aids, stimulants, and other
      medications that may be used in the cardiac transplant recipient. CONCLUSIONS:
      Many OTC medications can be used safely in the cardiac transplant recipient. In
      each situation, risk/benefit assessments must always be made and therapy should
      be monitored closely. Most important, patients should always notify the
      transplant team before adding an OTC product to their immunosuppressive regimen.

PMID- 1362367
TI  - Recent progress in the molecular genetics of the muscular dystrophies.

PMID- 1362368
TI  - Depletion of T-lymphocyte subsets in murine herpes-simplex-virus retinitis.
AB  - Uniocular injection of herpes-simplex virus type 1 into the anterior chamber of
      BALB/c mice induced contralateral retinitis with relative preservation of the
      ipsilateral retina. Overall 95% of T-cell deficient nude mice developed ipsi- and
      contralateral retinitis, suggesting the importance of T-cells in this model. We
      then depleted lymphocyte subsets in susceptible BALB/c and resistant CB-17 and
      C57BL/6J mice using anti-CD4 (helper/inducer cells) or anti-CD8
      (suppressor/cytotoxic cells) monoclonal antibody. 85% of CD8-depleted, 58% of CD4
      depleted and 50% of untreated BALB/c mice developed contralateral retinitis. All
      CD4- and CD8-depleted animals developed severe ipsilateral retinitis. These
      results suggest that CD8 cells (but not CD4 cells) are protective for the
      contralateral retina in BALB/c mice and that both subsets are important for the
      ipsilateral protection. In CB-17 and C57BL/6J mice, depletion produced no change
      in the contralateral retina but resulted in ipsilateral retinitis, suggesting
      different mechanisms for ipsi- and contralateral protection. The possible role of
      the anterior-chamber-associated immune deviation is discussed.

PMID- 1362369
TI  - Relationship between iron status and chronic akathisia in an in-patient
      population with chronic schizophrenia.
AB  - Iron status and akathisia were assessed in 105 long-stay in-patients who
      fulfilled DSM-III-R criteria for schizophrenia, all but three of whom were
      receiving antipsychotic medication. Chronic akathisia was diagnosed in 23% and
      pseudoakathisia in 20%. No significant correlation was found between serum iron
      concentration and the severity of akathisia. There was no significant difference
      in serum iron concentration between patients with chronic akathisia and those
      without. However, serum iron and percentage saturation were significantly raised
      in patients with pseudoakathisia compared with patients with chronic akathisia,
      and tended to be higher than in patients with akathisia. These findings do not
      support an association between low serum iron and chronic akathisia.

PMID- 1362370
TI  - Clozapine rechallenge after an episode of 'neuroleptic malignant syndrome'.
AB  - Nine out of 4044 patients admitted to our institution between 1987 and 1990
      suffered an episode of NMS. Neuroleptic rechallenge using clozapine for
      persisting psychiatric illness was tolerated by eight patients. Clozapine was
      discontinued in one older, high-risk patient because recurrence of NMS was
      anticipated. Clozapine should be considered a drug of choice for psychotic
      patients with a history of NMS.

PMID- 1362371
TI  - Botulinum toxin in a case of severe tardive dyskinesia mixed with dystonia.

PMID- 1362373
TI  - Symposium on diseases related to ultraviolet radiation: a risk-management
      approach.

PMID- 1362372
TI  - Use of radiography in acute ankle injuries: physicians' attitudes and practice.
AB  - OBJECTIVES: To examine the efficiency of the current use of radiography in
      patients with acute ankle injury. To study the judgements and attitudes of
      experienced clinicians in their use of ankle radiography and to thereby assess
      the potential for improved efficiency. DESIGN: Two-stage study: retrospective
      chart review and prospective survey. SETTING: Emergency departments of two adult
      teaching hospitals and one community hospital. PARTICIPANTS: The records of 1831
      adults presenting with acute blunt trauma to the ankle over 5 months were
      examined; another 732 patients were seen by 21 full-time emergency staff
      physicians over a subsequent 6-month period. MEASURES AND MAIN RESULTS: Of the
      1831 patients with an ankle injury in stage 1, 94.9% had had at least one
      radiographic series; the yield for clinically important fractures was 12.8%. In
      stage 2, experienced physicians predicted the probability of fracture to be 0% or
      10% in 57.8% of cases. The kappa (kappa) level for interobserver agreement in 98
      patients seen independently by two physicians was 0.55 (95% confidence interval
      [CI] 0.39 to 0.72). The area under the receiver operating characteristic curve
      for physicians' predicted probability was 0.88 (95% CI 0.84 to 0.92), reflecting
      good discrimination between fracture and nonfracture cases. Likelihood ratios for
      predicted probabilities ranged from 0.08 for the 0% level to 151 for the 100%
      level. The physicians indicated that they would feel comfortable or very
      comfortable in not ordering radiography in 45.9% of cases (kappa level 0.52; 95%
      CI 0.34 to 0.70). CONCLUSIONS: Emergency physicians order radiography for most
      patients with ankle injury even though they can accurately discriminate between
      fracture and nonfracture cases and clearly expect most of the radiographs to give
      normal results. These findings suggest great potential for a more efficient use
      of radiography in patients with ankle injury, possibly through the use of
      guidelines.

PMID- 1362374
TI  - Spin echo nuclear magnetic resonance studies on intact erythrocytes: changes in
      cellular metabolism as a consequence of carbimazole therapy.
AB  - OBJECTIVE: Because the exact mechanism of action of carbimazole is uncertain,
      nuclear magnetic resonance (NMR) spectroscopy was used to investigate cellular
      changes in erythrocytes from Graves' patients following a course of carbimazole
      therapy. DESIGN: NMR spectroscopy was carried out using intact erythrocytes
      obtained from Graves' patients prior to and at 2 and 12 months after carbimazole
      treatment. The data were correlated with thyroid hormone and antibody levels.
      PATIENTS: Twenty patients (four males; 16 females) with newly diagnosed and
      previously untreated Graves' disease were enrolled into the study. Assessments
      were made prior to the commencement of therapy and after 2 and 12 months on
      treatment. Of the 20 patients assessed at 0 and 2 months only 12 completed the
      study. MEASUREMENTS: The oxidation-reduction balance of erythrocyte glutathione
      was measured directly using 1H spin echo NMR spectroscopy of intact cells.
      Thyroid hormone and antibody levels were measured using reported methods.
      RESULTS: At 2 and 12 months a significant (P < 0.01) oxidation of the erythrocyte
      glutathione was observed. Of the four thyroid related markers (T3, T4, TRAb and
      TSH) assessed in this study both T3 (P < 0.001) and TRAb (P < 0.001) were
      observed to correlate with the NMR observed changes in glutathione. However, in
      vitro experiments indicated that carbimazole does not affect red cell glutathione
      directly. CONCLUSIONS: A model is presented which uses the hydrated iodium cation
      (I+), the natural product of T4 conversion to T3, as a chemical oxidant which can
      produce the observed clinical alteration in intracellular glutathione in ex-vivo
      erythrocytes. It is suggested that a major factor in the action of carbimazole in
      Graves' disease may be to stimulate the function of the deiodinase enzymes.

PMID- 1362376
TI  - Clinical pharmacology of active variceal bleeding.
AB  - Although the mechanism initiating and maintaining variceal hemorrhage is not
      completely understood, there has been general agreement in recent years on the
      concept that variceal rupture occurs when the tension on the wall of the varices
      reaches a critical value (the rupture point) that leads to the leakage of the
      elastic components of the wall. If this hypothesis is true, the aim of
      pharmacological treatment should be to reduce variceal wall tension or to prevent
      any abrupt increase in this parameter. Some vasoconstrictor drugs are currently
      used in order to achieve these goals and in the attempt to stop the acute
      bleeding episode. All these agents decrease either portal pressure and azygos
      blood flow. Vasopressin although effective, has significant cardiac and
      gastrointestinal adverse effects that discourage its use. Combination with
      nitroglycerin reduces its adverse effects while maintaining or even enhancing the
      reduction in portal pressure. Glypressin, which acts as a slow-release
      preparation of vasopressin, has a longer duration of action and can be
      administered as single intravenous injections instead of continuous infusion.
      However, the similarity of effects of these drugs on systemic circulation leads
      to an overlapping spectrum of untoward effects. Somatostatin and the synthetic
      octapeptide octreotide display similar pharmacological effects on splanchnic
      hemodynamics but have a better tolerability profile. Thanks to its longer
      duration of action and ease of administration, octreotide could become the drug
      of choice for the early, pre-hospital management of bleeding varices. A different
      approach to the pharmacological treatment of variceal bleeding may be the use of
      compounds, like metoclopramide and domperidone, that increase the lower
      esophageal sphincter pressure (LESP), thereby reducing the inflow of blood flow
      into the submucous venous plexus of the esophagus and hence into the esophageal
      varices. However, more studies are needed before these compounds be considered a
      real alternative to the above established drugs.

PMID- 1362375
TI  - Thyroid function tests are rarely abnormal in patients with severe hyperemesis
      gravidarum.
AB  - OBJECTIVES: There is considerable controversy in the literature as to the cause
      of hyperemesis gravidarum. The aim of this project was to measure a range of
      thyroid hormone levels in a group of hyperemetic pregnant women. PATIENTS: The
      study was carried out in 10 first trimester pregnant women with hyperemesis
      gravidarum. All had been admitted to hospital due to the severity of their
      symptoms. Fifty age matched, healthy first trimester pregnant women were used as
      controls. MEASUREMENTS: Blood samples from the women were analysed for total T3
      (TT3), total T4 (TT4), free T4 (FT4), TSH, thyrotrophin receptor antibodies
      (TRAb), thyroid stimulating antibodies (TSAb) and thyroid microsomal and
      thyroglobulin antibodies. Human chorionic gonadotrophin (hCG) levels were also
      measured. RESULTS: While individual patients were found to have some abnormal
      thyroid function tests the group as a whole showed no consistent pattern of
      abnormality and did not differ significantly from a group of healthy first
      trimester pregnant women. hCG levels were also within the normal range in the
      hyperemetic patients. DISCUSSION: None of the women in this study received any
      antithyroid medication and their symptoms improved as the pregnancy progressed.
      These results would suggest that there is no underlying thyroid abnormality in
      patients with hyperemesis gravidarum. It would appear that neither thyroid
      hormones, nor hCG contribute to the pathogenesis of the condition.

PMID- 1362377
TI  - Medical management of bleeding esophageal varices.
AB  - Vasoactive drug therapy is the only therapy that can be administered immediately
      to patients with suspected variceal bleeding. The optimal agent is not yet
      available, but somatostatin or octreotide, glypressin and vasopressin and
      nitroglycerin are the best candidates. Somatostatin and octreotide have the best
      therapeutic index as they have very few side effects. They compare well to the
      other agents in comparative randomized trials. In addition to being used prior to
      sclerotherapy, vasoactive agents may show benefit when used in combination with
      endoscopic methods and in the immediate interval thereafter in order to prevent
      early re-bleeding. This remains to be tested in clinical trials.

PMID- 1362379
TI  - Regulation of the Eukaryotic Cell Cycle. Ciba Foundation Symposium. London, 21-23
      January 1992.

PMID- 1362378
TI  - Prevention of upper gastrointestinal bleeding from portal hypertension in
      cirrhosis: rationale for medical treatment.
AB  - We updated meta-analysis and critical descriptive analysis of randomized clinical
      trials (RCTs) assessing the value of beta-blockers in preventing first bleeding
      (prophylactic) or rebleeding (therapeutic) and on survival of patients with
      cirrhosis. Both the methods of Peto-Mantel-Haenszel and DerSimonian-Laird were
      used to assess the heterogeneity and obtain cumulative estimates of treatment
      effects; the L'Abbe plot was also used for a visual assessment of heterogeneity
      in the direction of treatment effect. Seven prophylactic and nine therapeutic
      RCTs were analysed. beta-Blockers uniformly reduced the bleeding risk and
      revealed a trend toward improved survival in non-ascitic, well-compensated
      patients in both the prophylactic and therapeutic sets of RCTs. Discordant
      results were found in patients with ascites or in poor functional condition.

PMID- 1362380
TI  - Development of the D. melanogaster caudal segments involves suppression of the
      ventral regions of A8, A9 and A10.
AB  - Whereas the segmental organization of the thorax and anterior abdomen is
      morphologically delineated in both the Drosophila larva and adult, segments in
      the head and caudal regions lack such well-defined boundaries. Consequently, the
      organization of these regions has been difficult to decipher. In this study,
      transformations caused by the bithorax-complex homeotic mutants 48, M3,
      Ultraabdominal-1 (Uab1) and tumorous-head-3 (tuh-3), as well as the patterns of
      engrailed gene expression have been analyzed to investigate the segmental
      organization of the caudal segments. A special emphasis was placed on sense
      organs appearing in abdominal segments 8, 9 and 10 (A8-A10): We find that: (1)
      transformations in the caudal segments obey parasegmental borders; (2) the sense
      organs on A8, A9, and A10 are probably homologous to the pits and hairs in
      anterior A1-A7; (3) except for the larval anal tuft and the anterior side of A8,
      all structures in larval segments A8, A9 and A10 are dorsal/lateral in origin;
      and (4) dorsalization of embryonic A8 and A9 cells leaves space ventrally for
      A10, as it follows the contracting ventral nervous system during the
      embryological process of germ band contraction.

PMID- 1362381
TI  - A dominant mutation in the maize homeobox gene, Knotted-1, causes its ectopic
      expression in leaf cells with altered fates.
AB  - Dominant mutations of the Knotted-1 (Kn1) homeobox gene of maize alter the
      differentiation and growth of cells associated with leaf veins. By analyzing Kn1
      transcripts and KN1 protein, we show that the gene is not expressed at high
      levels during the development of wild-type leaves. Instead, Kn1 is expressed in
      apical meristems of vegetative and floral shoots, and is downregulated as leaves
      and floral organs are initiated. Kn1 is also expressed in relatively
      undifferentiated cells within developing vascular bundles, as well as ground
      tissue, in immature, unelongated axes of wild-type vegetative and floral shoots.
      In Kn1-N2 mutant plants, quantitative, but not qualitative differences are
      apparent in Kn1 transcripts and KN1 protein, consistent with previous
      observations that dominant Kn1 mutations map to non-coding regions of the gene.
      Kn1 is expressed ectopically in vascular bundles within developing mutant leaves
      in a pattern that correlates with the phenotypic alterations produced by the Kn1
      N2 mutation. Thus, Kn1 apparently alters the fates of leaf cells in which it is
      ectopically expressed from an early stage of leaf development. Based on these
      observations, we hypothesize that Kn1 functions in its wild-type context as a
      regulator of cell determination.

PMID- 1362382
TI  - Peroxisomal acetoacetyl-CoA thiolase of an n-alkane-utilizing yeast, Candida
      tropicalis.
AB  - Two genes encoding acetoacetyl-CoA thiolase (thiolase I; EC 2.3.1.9), whose
      localization in peroxisomes was first found with an n-alkane-utilizing yeast,
      Candida tropicalis, were isolated from the lambda EMBL3 genomic DNA library
      prepared from the yeast genomic DNA. Nucleotide sequence analysis revealed that
      both genes contained open reading frames of 1209 bp corresponding to 403 amino
      acid residues with methionine at the N-terminus, which were named as thiolase IA
      and thiolase IB. The calculated molecular masses were 41,898 Da for thiolase IA
      and 41,930 Da for thiolase IB. These values were in good agreement with the
      subunit mass of the enzyme purified from yeast peroxisomes (41 kDa). There was an
      extremely high similarity between these two genes (96% of nucleotides in the
      coding regions and 98% of amino acids deduced). From the amino acid sequence
      analysis of the purified peroxisomal enzyme, it was shown that thiolase IA and
      thiolase IB were expressed in peroxisomes at an almost equal level. Both showed
      similarity to other thiolases, especially to Saccharomyces uvarum cytosolic
      acetoacetyl-CoA thiolase (65% amino acids of thiolase IA and 64% of thiolase IB
      were identical with this thiolase). Considering the evolution of thiolases, the
      C. tropicalis thiolases and S. uvarum cytosolic acetoacetyl-CoA thiolase are
      supposed to have a common origin. It was noticeable that the carboxyl-terminal
      regions of thiolases IA and IB contained a putative peroxisomal targeting signal,
      -Ala-Lys-Leu-COOH, unlike those of other thiolases reported hitherto.

PMID- 1362383
TI  - Predominant beta-adrenoceptor blocking effect of xamoterol averaged over the day
      in patients with mild to moderate heart failure: insight into the mechanism of
      its long-term clinical efficacy.
AB  - Xamoterol acts as a beta 1-adrenoceptor agonist at low sympathetic activity and
      as an antagonist at high activity. Although its long-term efficacy has been
      proven in patients with mild to moderate heart failure, it remains unclear which
      effect, agonism or antagonism, accounts for its long-term activity. To clarify
      the effect of xamoterol on cardiac sympathetic activity in daily life, 24-h R-R
      interval histograms were obtained during administration of xamoterol 100 mg b.d.
      for 1 week to 10 patients with mild to moderate heart failure. Eight normal
      subjects were also studied as controls. To examine the relation between the
      effect of xamoterol and sympathetic activity, plasma noradrenaline (NA) levels
      were measured under 5 graded conditions simulating daily living. Xamoterol
      administration significantly decreased the standard deviation of the R-R
      interval, both in patients with heart failure and in normal subjects. The mean R
      R interval, however, was increased in patients with heart failure, relative to
      normal subjects. In both groups, the R-R interval histograms had two peaks, i.e.
      a short daytime peak and a long night-time peak. Xamoterol decreased the median
      of the night-time peak without changing the daytime peak in normal subjects. In
      contrast, it increased the median of the daytime peak without producing a
      significant change in the night-time peak in patients with heart failure. Levels
      of plasma NA were significantly higher in patients than in normal subjects under
      all conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362384
TI  - Enantioselective pharmacokinetics of homochlorcyclizine. II: Disposition and
      metabolism of (+)-, (-)- and racemic homochlorcyclizine after oral administration
      to man.
AB  - The pharmacokinetics of a single oral dose of 20 mg (+)-, (-)- and racemic
      homochlorcyclizine (HCZ) have been studied in humans. The formation of the
      quarternary ammonium-linked glucuronide was an important metabolic pathway, and
      the metabolic process was enantioselective as a result of differing urinary
      excretion rates of (+)-, (-)- and racemic glucuronide. There were significant
      differences between (+)-, (-)- and racemic HCZ in AUC (0-14 h) and plasma protein
      binding, but all HCZ enantiomers were slowly absorbed and eliminated (elimination
      half-lives about 11 h). The results shows help to establish a more efficient
      dosage regimen for HCZ therapy.

PMID- 1362385
TI  - Biological and clinical features of B-precursor childhood acute lymphoblastic
      leukemia showing CD2 and/or E-rosette co-expression.
AB  - BACKGROUND: Co-expression of the T-associated marker CD2 or E-rosette in non-T
      acute leukemia has rarely been reported. In this paper the incidence of such co
      expression, together with its biologic features and clinical relevance, was
      evaluated in a large series of childhood "common" acute lymphoblastic leukemia
      (cALL) cases. METHODS: This analysis was performed retrospectively on 306 cases
      of childhood non-T ALL. CD2 and/or E-rosette co-expression with other non-T
      markers was usually shown by a clear overlap between the percentages of T and non
      T markers, by the great difference between positivity for CD2 or E-rosette and
      other T markers, and by double staining for CD2 and CD10 in one case. Two cases
      were further studied by a panel of nine different CD2 monoclonal antibodies
      (MAbs) representative of different epitopes. DNA analysis for the configuration
      of Ig and TCR genes (beta, gamma, and delta locus) was carried out in three
      cases. RESULTS: Eleven out of 306 cases (3.6%) showed CD2 and/or E-rosette co
      expression in otherwise typical cALL. Data obtained in two cases with the use of
      nine different CD2 Mabs showed a different pattern of reactivity between leukemic
      B cells and normal T cells. The configuration of Ig and TCR genes was compatible
      with B-lineage ALL. CONCLUSIONS: CD2 and/or E-rosette co-expression was observed
      in a small subset of acute leukemias showing immunophenotypic and genotypic
      features of B-lineage ALL. A pattern of reactivity different from that seen in
      normal T cells was observed in the two cases tested with a large panel of CD2
      MAbs. No association was found with other known prognostic factors, and 8 of
      these 11 patients have been in first continuous remission for 36-93 months.

PMID- 1362386
TI  - [A study of the chromosomal location of a gene responsible for hypertrophic
      cardiomyopathy].
AB  - Hypertrophic cardiomyopathy (HCM) is defined as a disorder with nondilated left
      ventricular hypertrophy in the absence of any overt cause, and diagnosed by
      clinical symptoms (chest pain, syncope, et al.), past history,
      electrocardiography and two-dimensional echocardiography. About 50% of HCM
      (familial HCM) has a familial occurrence with an autosomal mode of inheritance.
      To investigate the causative genes of familial HCM, we have performed a linkage
      analysis by using RFLP (Restriction Fragment Length Polymorphism) method. In this
      method, DNA markers which are mapped to one region of the human genome with the
      known location were used to identify DNA markers linked to the causative loci for
      familial HCM. The linkage analysis was performed by calculating a lod score,
      using LIPED program. Thirteen families with familial HCM, composed of HCM
      patients, were studied by RFLP method. The maximum lod score of PALB, which is
      located on chromosome 18q11.2-12.1 was 3.672, although those of the other DNA
      markers were below-2 at a recombination fraction of 0.00 with complete
      penetrance. These results strongly suggest that the causative gene for familial
      HCM is closely linked with PALB and expected to facilitate the identification and
      cloning of the causative genes of familial HCM.

PMID- 1362387
TI  - Alcohol dehydrogenase genes: restriction fragment length polymorphisms for ADH4
      (pi-ADH) and ADH5 (chi-ADH) and construction of haplotypes among different ADH
      classes.
AB  - Of the five human alcohol dehydrogenase (ADH) genes located in the region q21-25
      of chromosome 4, genetic markers have been reported previously only for class I
      enzymes, ADH1-3. Here, new restriction fragment length polymorphisms (RFLPs) are
      described for the genes of two other classes, ADH4 (pi) and ADH5 (chi or
      formaldehyde dehydrogenase, FDH). The frequencies and modes of inheritance of
      these RFLPs were determined with DNA both from unrelated individuals and from
      families. A polymorphic PstI site is assigned to the fourth intron of the ADH4
      gene. Pairwise linkage disequilibrium calculations for these new RFLPs and
      already known RFLPs at the ADH2 and ADH3 loci establish strong linkage
      disequilibria between polymorphic MspI and BstXI sites in the ADH5 gene as well
      as between XbaI and MspI sites in the ADH3 gene. Furthermore, linkage
      disequilibria were detected between RFLPs of the ADH2 and ADH3 genes as well as
      between those of the ADH4 and ADH5 genes. The latter disequilibrium implies a
      hitherto unknown physical proximity of two genes belonging to different ADH
      classes. The RFLPs were used to construct chromosomal haplotypes that include
      three ADH classes. Of the 16 possible haplotypes for four RFLP markers used here,
      10 were experimentally detected. The potential application of the ADH RFLPs and
      haplotypes in linkage or association studies of inherited diseases such as
      familial "alcoholism" is discussed.

PMID- 1362389
TI  - Oral Health Care for the Elderly. Proceedings of a symposium. Oslo, Norway, 27-29
      March 1992.

PMID- 1362391
TI  - Physiology of Mountain Sports. Proceedings of the International Congress on
      Mountain Sports. Chamonix, France, 2-4 February 1992.

PMID- 1362390
TI  - Summary of group work and plenary sessions.

PMID- 1362392
TI  - Synthesis and pharmacological activity of the N-terminal dermorphin tetrapeptide
      analogs with CH2-NH peptide bond isosteres.
AB  - The synthesis of pseudotetrapeptides H-Tyr-D-Ala-Phe-NH-(CH2)2--NH2 (1a), H-Tyr-D
      Ala-Phe-psi (CH2--NH)-Gly-NH2 (2a), H-Tyr-D-Ala-psi (CH2--NH)-Phe-Gly-NH2 (3a),
      and H-Tyr-psi (CH2--NH)-D-Ala-Phe-Gly-NH2 (4a), representing the N-terminal
      tetrapeptide sequence of dermorphin, in which amide bonds are replaced by CH2--NH
      bond, is described. N-acetyl-Tyr and desamino-Tyr pseudopeptide analogs (1-4b),
      (1-3c) are also described. The analogs were assayed in binding studies based on
      displacement of mu and delta-receptor selective radiolabels from rat brain
      membrane and in a bioassay using guinea pig ileum (GPI). Pseudopeptides in which
      the C-terminal (1a) or D-Ala-Phe (3a) amide bond are substituted, exhibit higher
      mu-affinities and mu-receptor selectivity than the corresponding Phe-Gly or Tyr-D
      Ala analogs (2a, 4a). Acetyl-and desamino-Tyr pseudopeptide analogs (1-4b) and (1
      3c) did not exhibit mu and delta-opioid receptor affinity at nM concentration.
      The relevance of the single peptide replacement and of its association to
      acetylation or amino group elimination of Tyr, is discussed on the basis of a
      receptor model for mu and delta opioids.

PMID- 1362388
TI  - Analysis of beta-globin gene haplotypes in Asian Indians: origin and spread of
      beta-thalassaemia on the Indian subcontinent.
AB  - beta-globin gene haplotypes were determined for 196 normal (beta-A) and 419
      thalassaemia (beta-Th) chromosomes of individuals from four different regions of
      the Indian subcontinent; North-west Pakistan, Gujarat, Punjab and Sindh. Analysis
      of beta-A and beta-Th haplotypes and haplotype-mutation associations in each
      regional group along with a consideration of Indian history provided information
      about the origin and spread of beta-thalassaemia mutations on the Indian
      subcontinent. The data are consistent with relatively recent and local origins
      for most beta-thalassaemia mutations. The frequencies of particular alleles
      differ markedly in various regions and these may be useful population markers. Of
      the high frequency alleles, intervening sequence 1 (IVS-1) nucleotide 5 (G-C) and
      codons 41/42 (-CTTT) appear to be older as suggested by multiple haplotype
      associations and a widespread geographical distribution. The microepidemiology of
      beta-thalassaemia in this region reflects considerable ethnic diversity, gene
      flow from population migration and natural selection by malaria infection.

PMID- 1362393
TI  - Synthesis of alpha-, beta- and cyclic spaglumic acids.
AB  - A short, one-pot synthesis of alpha- and beta-spaglumic acids (N-acetyl-L
      aspartyl-L-glutamic acids, NAAGA) has been developed based on ultrasound-promoted
      acetylation of aspartic acid, followed by dehydration, condensation with glutamic
      acid dibenzyl ester and hydrogenolysis. The alpha- and beta-peptides were
      separated by anion-exchange chromatography. The alpha-peptide shows a remarkable
      tendency to cyclize during methylation with diazomethane and yields cyclic N
      acetylaspartylglutamic acid dimethyl ester, which could be hydrolysed to the
      hitherto unreported diketopiperazine dicarboxylic acid, cyclic spaglumic acid
      (cyclic NAAGA).

PMID- 1362394
TI  - A multicenter Italian randomised study on early treatment of Parkinson disease:
      comparison of L-dopa, l-deprenyl and dopaminoagonists. Study design and short
      term results. The Italian Parkinson Study Group.
AB  - On the long term Parkinson Disease (PD) treatment is often complicated by the
      occurrence of motor fluctuations. To find out whether early treatment of PD with
      levodopa, dopaminoagonists or l-deprenyl is associated with any difference in
      motor fluctuations occurrence, the Italian Parkinson Study Group initiated a
      multicenter, randomized study. Since November 1988, 475 patients requiring
      effective treatment for idiopathic PD have been randomized to receive levodopa,
      dopamine agonists or deprenyl. After 2 months of therapy, all patients evaluated
      with the Unified Parkinson Disease Rating Scale showed a significant
      amelioration. Daily living activities were more impaired in patients treated with
      deprenyl. Study design is presented and first results are discussed.

PMID- 1362396
TI  - Sublocalization of the multiple endocrine neoplasia type 1 gene.
AB  - Tumorigenesis in multiple endocrine neoplasia type 1 (MEN 1) involves the
      unmasking of a recessive mutation at the MEN 1 locus which has been mapped to
      chromosomal region 11q11-13. By analyzing 58 DNA markers on a panel of radiation
      reduced somatic cell hybrids, the region encompassing the MEN 1 gene was divided
      into nine subregions. Pulsed field gel electrophoresis analysis of markers within
      subgroups showed that the recombination rate around the MEN 1 locus is high.
      Combined linkage analysis in MEN 1 families and deletion mapping in MEN 1-related
      tumors suggest the MEN 1 gene is located centromeric to D11S807 and telomeric to
      PYGM.

PMID- 1362395
TI  - Neurosciences and Pain. 1st Meeting. Rome, Italy, 2-3 October 1992. Abstracts.

PMID- 1362397
TI  - Molecular genetic mapping of the multiple endocrine neoplasia type 1 locus.
AB  - Familial multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant
      disorder characterized by the combined occurrence of tumors of the parathyroid
      glands, the endocrine pancreas, and the pituitary gland. MEN 1 tumors have
      previously been shown to be associated with the loss of alleles on chromosome 11,
      and deletion mapping studies together with family linkage studies have localized
      the MEN 1 gene to 11q13. A detailed genetic map around the MEN 1 locus is
      required to facilitate further characterization and cloning of the gene (MEN1).
      We have characterized a panel of seven rodent-human somatic cell hybrids which
      contain fragments of human chromosome 11 with breakpoints in the pericentromeric
      region by using eight DNA sequences (D11S149, PGA, PYGM, D11S97, INT2, D11S37,
      D11S533, and D11S147) to define the region containing MEN1. This will facilitate
      the rapid localization of additional DNA sequences in this region. In addition,
      we have used a highly polymorphic repetitive degenerate hexanucleotide sequence,
      designated D11S533, for segregation studies in one family with MEN 1. These
      molecular genetic approaches will help to define a precise 1 to 2 centiMorgan map
      around MEN1.

PMID- 1362398
TI  - Prospective screening in multiple endocrine neoplasia type 1.
AB  - To assess the age of clinically detectable onset of multiple endocrine neoplasia
      type 1 (MEN 1), 88 members of four families were invited to participate in a ten
      year biochemical screening program. Evidence for clinically detectable MEN 1 was
      found in adolescence. Pancreatic endocrine dysfunction constituted the presenting
      lesion in a majority of these individuals. The age at diagnosis of pancreatic
      endocrine tumors averaged 25 years and was lowered by almost two decades by
      prospective investigation. Furthermore, the penetrance of the pancreatic
      endocrine and parathyroid lesions equaled the penetrance found in autopsy
      studies. The use of a standardized meal stimulation test with the measurement of
      serum pancreatic polypeptide (PP) and gastrin responses resulted in diagnostic
      sensitivities of 75% and 100%, respectively. In addition to basal serum PP and
      insulin values, the proinsulin level was predictive for early pancreatic
      involvement in MEN 1. Serum gastrin was another useful tumor marker but only in
      the patients with pancreatic tumors diagnosed outside the prospective
      investigation. Two of the four MEN 1 kindreds selected for the screening
      investigation displayed homogeneity within families with respect to the profile
      of peptide excess and malignant potential of the pancreatic endocrine lesion,
      while the remaining kindreds demonstrated variable MEN 1 traits.

PMID- 1362399
TI  - The importance of screening for the MEN 1 syndrome: diagnostic results and
      clinical management.

PMID- 1362401
TI  - Parathyroid tumor biology in familial multiple endocrine neoplasia type 1: a
      model for cancer development.
AB  - Familial multiple endocrine neoplasia type 1 (FMEN 1) is an autosomal dominant
      disorder characterized by tumors of the parathyroid glands, pancreatic islets,
      and anterior pituitary. Hyperplasia appears to be the typical histopathological
      lesion in FMEN 1 endocrine tumors. A circulating mitogen related to basic
      fibroblast growth factor was active on proliferation of clonal bovine and human
      parathyroid endothelial cells. Moreover, the FMEN 1 mitogen modulated
      differentiation of human parathyroid endothelial cell in vitro. All these facts
      suggested that an extrinsic factor was active on parathyroid endothelial cell
      growth and differentiation. The FMEN 1 gene maps to chromosome 11q13, and allelic
      loss in this region has been shown in FMEN 1 parathyroid and pancreatic islet
      tumors and rarely in anterior pituitary tumors. Together these results support
      the theory that FMEN 1 parathyroid clonal lesions can develop in the context of
      generalized hyperplasia. Similarly, in uremic hyperparathyroidism, where
      parathyroid hyperplasia is thought to be the primary lesion, loss of
      constitutional heterozygosity for chromosome 11 markers coexists in parathyroid
      tissue with a polyclonal pattern. Future efforts of scientists working on this
      genetic disorder will focus on the cloning of the FMEN 1 gene and the development
      of a suitable bioassay system to study its function.

PMID- 1362400
TI  - Practical guidelines for DNA-based testing in multiple endocrine neoplasia type
      1.
AB  - Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant
      predisposition to neoplastic lesions of the parathyroid glands, the
      neuroendocrine pancreas, and the anterior pituitary gland. The predisposing
      genetic defect was localized to the long arm of chromosome 11 by genetic linkage
      analysis in three affected families. By analyzing six MEN 1 families with 14 DNA
      marker systems located close to the MEN 1 gene, we have developed a method to
      identify carriers of the MEN 1 predisposition. We describe practical aspects of
      such DNA-based diagnostic procedures.

PMID- 1362402
TI  - Hyperparathyroidism with normal albumin-corrected total calcium in patients with
      multiple endocrine neoplasia type 1.
AB  - In the largest reported family of patients with multiple endocrine neoplasia type
      1 (MEN 1), hyperparathyroidism was expressed at first screening in 33 patients by
      elevation of ionized calcium (IC) (30 cases) or parathyroid hormone (three cases)
      without elevation of albumin-corrected total calcium (ACTC). Three of these 33
      patients have shown a progressive rise in IC and later an elevation of ACTC.
      However, the age distribution suggests that in others the level of IC may remain
      stable at a minimally elevated level throughout life with ACTC remaining normal
      except for transient rises at the times of intercurrent illness or surgical
      operation. Even when ACTC is normal preoperatively, patients with an elevation of
      IC require radical subtotal parathyroidectomy or total parathyroidectomy and
      forearm implantation to restore IC to a normal level. Institutions that rely on
      ACTC as a screening test for hyperparathyroidism in MEN 1 will miss the diagnosis
      in nearly half of patients under the age of 30. The greatest deficiency in using
      ACTC occurs in the follow-up of patients who have undergone parathyroidectomy for
      MEN 1. Only three of 11 recurrences were evidenced by this measurement.

PMID- 1362403
TI  - Primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1:
      experience by a single surgical team in Japan.
AB  - Nineteen patients were surgically treated for hyperparathyroidism associated with
      multiple endocrine neoplasia type 1 syndrome. Fourteen patients (74%) had removal
      of three or more parathyroid glands at the first operation, and five (26%) by
      removal of 2 1/2 or fewer glands. Two patients had recurrent hypercalcemia during
      the mean follow-up period of 65 months. One had a recurrence 10 years after
      subtotal parathyroidectomy. Reexploration in this patient revealed enlargement of
      the remaining tissue in the neck and an enlarged supernumerary gland in the
      aorticopulmonary window. The other patient had persistent hypercalcemia after
      removal of two hyperplastic parathyroid glands until after another 1 1/2 more
      glands were removed. After reoperation the patient was normocalcemic for 10 years
      before hypercalcemia was again noticed. The patient subsequently died from renal
      carcinoma metastases, which might have been the cause of the hypercalcemia before
      death.

PMID- 1362404
TI  - Surgical treatment of the endocrine pancreas and Zollinger-Ellison syndrome in
      the MEN 1 syndrome.
AB  - Islet cell neoplasia is a frequent occurrence in multiple endocrine neoplasia
      type 1 (MEN 1). Sixteen of 27 patients with MEN 1 developed functioning endocrine
      pancreatic tumor syndromes. Eleven of the 16 developed Zollinger-Ellison syndrome
      and each was evaluated by a combination of computed tomography and hepatic
      angiography to exclude hepatic metastasis and percutaneous transhepatic
      catheterization to localize the tumor. Seven of the 11 patients were found to
      have duodenal gastrinomas with multiple duodenal tumors in three patients. Four
      of the 11 patients had only pancreatic gastrinomas. In addition to the
      gastrinomas, other types of islet tumors in the pancreatic body or tail were
      found in nine of the 11 patients. None of the patients had hepatic metastases.
      Seven of the 11 patients were treated by distal pancreatectomy and since 1986 all
      patients have had duodenotomies as part of the surgical exploration. Postsurgical
      evaluation ranging from three months to 14 years indicates that 10 of 11 patients
      have normal basal gastrin levels. We conclude that duodenal gastrinomas are
      common in MEN 1 and can be managed successfully by appropriate operative
      intervention.

PMID- 1362405
TI  - Localization of the gene for MEN 2A.
AB  - The search for the gene that causes the multiple endocrine neoplasia type 2A (MEN
      2A) syndrome is entering a new phase. Genetic linkage studies have localized the
      gene to the pericentromeric region of chromosome 10. The statistical portion of
      mapping the gene for MEN 2A is nearly complete and now classical molecular
      biological/gene mapping techniques will be employed. We have used fluorescence in
      situ hybridization to estimate the size of the MEN2A region to be about 2 to 5
      mb, using some liberal assumptions; at worst the region should contain no more
      than about 10 mb of non-alphoid DNA. Our mapping panels (meiotic recombinant and
      radiation reduced hybrid) give consistent orders of markers in this small region.
      We describe our initial attempts to clone the region using yeast artificial
      chromosomes.

PMID- 1362406
TI  - A preliminary analysis of consortium data for markers tightly linked to multiple
      endocrine neoplasia type 2A.
AB  - We have analyzed DNA marker typing data contributed by six independent groups to
      estimate the pairwise genetic distances between these markers and the locus for
      multiple endocrine neoplasia type 2A (MEN 2A). We used LIPED to calculate these
      distances for female, male, and sex-average linkage maps and to determine the
      corresponding LOD scores. The preliminary analyses of this large data set (89 MEN
      2A families and five non-MEN 2A references families, with 1,934 total
      individuals) are reported here. These refined estimates of the genetic map in
      this region will aid in the assignment of presymptomatic diagnoses. This study
      clearly points out the limitation of pairwise linkage analysis in further
      refining the position of MEN2A in this small region of chromosome 10. Further
      refinement of the genetic map position of MEN2A will be best accomplished by
      finding, verifying, and accurately mapping crossovers in specific families.

PMID- 1362407
TI  - Isolation of YAC clones from the pericentromeric region of chromosome 10 and
      development of new genetic markers linked to the multiple endocrine neoplasia
      type 2A gene.
AB  - Genetic linkage mapping and contig assembly using yeast artificial chromosome
      (YAC) technology form the basis of our strategy to clone and define the genomic
      structure of the pericentromeric region of chromosome 10 containing the multiple
      endocrine neoplasia type 2A gene. Thus far YAC walks have been initiated from
      five chromosome 10 pericentromeric loci including RBP3, D10S94, RET, D10Z1, and
      FNRB. Long range pulsed-field gel electrophoresis maps are constructed from the
      YACs isolated to define clone overlaps and to identify putative CpG islands.
      Bidirectional YAC walks are continued by rescreening the YAC library with
      sequence-tagged site assays developed from end-clones. Several new restriction
      fragment length polymorphisms and simple sequence repeat polymorphism markers
      have been identified from the YAC clones. In particular, two highly informative
      (CA)n dinucleotide repeat markers, sTCL-1 from proximal chromosome 10p (16
      alleles, PIC = 0.68) and sJRH-1 from the RBP3 locus (18 alleles, PIC = 0.88),
      provide useful reagents for a polymerase chain reaction-based predictive genetic
      test that can be performed rapidly from small amounts of DNA.

PMID- 1362409
TI  - Medullary thyroid carcinoma: Australian experience with genetic testing.
AB  - Linkage analysis has been performed in four pedigrees with multiple endocrine
      neoplasia type 2A (MEN 2A) or familial medullary thyroid carcinoma (MTC) using
      pericentromeric chromosome 10 probes. Important information regarding carrier
      status has been provided in 10 individuals, many of whom would not have been
      identified by pentagastrin stimulation testing. We have also used pulsed field
      gel electrophoresis (PFGE) to link the probes H4.IRBP and pMCK2 to a 150 kb
      fragment. Using PFGE, no evidence was found in DNA from lymphocytes of a major
      DNA rearrangement in two individuals affected with MEN 2A and an individual with
      MEN 2B compared with normals. Metastatic MTC from one patient has been used to
      generate a cDNA library which will be used to screen for candidate MEN 2A and MEN
      2B gene(s).

PMID- 1362408
TI  - Expression of the ret proto-oncogene in human medullary thyroid carcinomas and
      pheochromocytomas of MEN 2A.
AB  - We studied the expression of the ret proto-oncogene (proto-ret) in human
      medullary thyroid carcinomas (MTCs) and pheochromocytomas of multiple endocrine
      neoplasia type 2A (MEN 2A) by Northern blot analysis. Expression of the normal
      sized transcripts was detected in all 12 MTCs and in 6 of 8 pheochromocytomas. In
      situ localization of proto-ret mRNA revealed that the signal was confined to the
      cytoplasm of MTC cells. By Southern blot analysis neither amplification nor gross
      genetic changes of proto-ret were found in the tumors. Although no transcripts
      were detected in the normal portion of the thyroid from one MEN 2A patient, faint
      signals were detected in normal adrenal glands by Northern blot analysis,
      probably due to minor populations of C-cells and chromaffin cells in specimens
      from which MTC and pheochromocytoma might later develop. Proto-ret may play an
      important role in differentiation of a specific cell lineage from neuroectoderm,
      and it may be involved in development of MEN 2A tumors.

PMID- 1362410
TI  - Screening for multiple endocrine neoplasia type 2A with DNA-polymorphism
      analysis.
AB  - Nine chromosome 10 DNA markers (FNRB, D10S34, D10Z1, MEN203, D10S94, RBP3,
      D10S15, MBP [48.11], D10S22) were typed in two large Canadian pedigrees with
      multiple endocrine neoplasia type 2A (MEN 2A). These markers and the gene for MEN
      2A (MEN2A) are believed to be in one linkage group spanning approximately 15 cM
      (male). MEN203 and D10S94 were informative and tightly linked to MEN2A with no
      recombinants observed in 26 meiotic events. D10S15 (MCK2), widely used in DNA
      genotyping predictions, demonstrated two recombinants in these two families. The
      use of multiple flanking markers increases both the likelihood of informativeness
      and the accuracy of risk assessments for predictive testing. We were able to
      assign a risk estimate for all 10 at-risk individuals.

PMID- 1362411
TI  - High-sensitivity serum calcitonin assays applied to screening for thyroid C-cell
      disease in multiple endocrine neoplasia type 2A.
AB  - Two serum calcitonin assays with sensitivities < or = 10 pg/mL were compared to
      our standard radioimmunoassay (sensitivity 100 pg/mL) in multiple endocrine
      neoplasia type 2A (MEN 2A) screening. Values from the Nichols displacement
      radioimmunoassay averaged 38% higher than values from the CIS immunoradiometric
      assay; values from both were highly correlated, r = 0.845. In three individuals,
      both of the newer assays revealed abnormalities in pentagastrin tests three to
      four years before abnormalities were detected by the standard assay. Pentagastrin
      tests after total thyroidectomy were assayed by the newer methods in patients
      with medullary thyroid carcinoma (MTC) diagnosed at initial testing (group I); in
      patients with early MTC diagnosed by prospective screening (group II); and in
      patients with pure C-cell hyperplasia detected by prospective screening (group
      III). At least 64% of group I, at least 25% of group II, but none of group III
      had detectable postoperative C-cell function. CONCLUSIONS: 1) The previous
      estimate of 12 years as median age of onset of C-cell disease in MEN 2A is
      probably three to four years too old. 2) Patients diagnosed with early MTC by
      screening had not necessarily skipped a preneoplastic phase of C-cell
      hyperplasias. At least some early disease was not detected by the standard assay.
      Higher sensitivity assay should improve screening for C-cell disease by earlier
      disease detection. 3) Biochemical cure by thyroidectomy after the development of
      MTC is not as frequent as previously thought, but the apparent cure rate of pure
      C-cell hyperplasia remains 100%.

PMID- 1362412
TI  - Genetics of the multiple endocrine neoplasia type 2B syndrome.
AB  - Multiple endocrine neoplasia type 2B (MEN 2B) is similar to MEN 2A in that both
      autosomal dominant syndromes include medullary thyroid cancers and
      pheochromocytomas. It is distinct in that MEN 2B patients have much earlier age
      of onset with more aggressive tumors and mucosal neuromas of the lips and tongue.
      The neuromas allow ascertainment generally before age 5. Studies of two and three
      generations of 14 MEN 2B families disclosed close linkage of the MEN 2B gene to
      DNA markers to which MEN2A had been linked. Multipoint analysis utilizing
      additional results in three generations of a 15th family have disclosed a peak
      total lod score of 8.89 at the midpoint between the centromere markers D10Z1 and
      RBP3 on the long arm (band q11). One recombinant was observed between D10Z1 and
      MEN2B, but this individual was not recombinant with D10S94. These studies suggest
      physical proximity of MEN2A and MEN2B but do not establish allelism for the
      gene(s).

PMID- 1362413
TI  - Multiple endocrine neoplasia type 2B: eighteen-year follow-up of a four
      generation family.
AB  - Seven members with multiple endocrine neoplasia type 2B from a 15-member family
      have been followed for 18 years. All affected had the neuroma phenotype in a
      distribution compatible with autosomal dominant inheritance. The phenotype
      features have allowed 100% initial and continuing prediction of affected versus
      nonaffected status in as early as 1.5 years. Among the affected: immunoreactive
      plasma calcitonin (iCT) concentration was high in 100%; thyroid palpation was
      false-negative in 71%; and thyroid scintiscan was false-negative in 83%. All had
      total thyroidectomy, plus lymphadenectomy in three, for bilateral medullary
      thyroid carcinoma (MTC) or C-cell hyperplasia (in the youngest). None has died
      directly from MTC. The index case died at age 68 and his son at age 32 years from
      complications of the syndrome. All but the youngest have continuing high iCT
      concentrations. No patient has had parathyroid disease. During preoperative
      calcium infusion, immunoreactive serum parathyroid hormone concentration declined
      by 35% to 84% of basal. At operation, macroscopically and microscopically normal
      parathyroid glands were found in all. No patient has had chemical suggestion of
      pheochromocytomas: at postmortem the index case had no adrenal medullary disease;
      his son had bilateral nodular adrenal hyperplasia; his daughter has had adrenal
      medullary hyperplasia and a renin-secreting juxtaglomerular tumor. Initially
      nonaffected members remain so.

PMID- 1362414
TI  - Cutaneous lesion associated with multiple endocrine neoplasia type 2A: lichen
      amyloidosis or notalgia paresthetica?
AB  - Three patients of a French family demonstrated an association of multiple
      endocrine neoplasia type 2A (MEN 2A) with a pruritic scapular skin lesion. The
      lesions are similar to those described as familial cutaneous lichen amyloidosis
      in unrelated MEN 2A and medullary thyroid carcinoma families, but histological,
      immunohistochemical, and ultrastructural analysis of skin biopsies from each
      patient in the French family did not show amyloid deposition. The topography of
      the lesion follows dermatomes C8-D3. The patients report not only pruritus but
      also paresthesia and hyperalgesia, and one showed touch hypoesthesia and pain
      hyperesthesia in the area of the lesion. Such an association of cutaneous and
      neurological features suggests notalgia paresthetica (NP), a neuropathy of the
      posterior dorsal rami nerves. We thus suggest that the cutaneous lesions
      associated with MEN 2A might be secondary to pathology in the neural crest
      derived dorsal sensory nerves. The amyloid, when present, would be secondary to
      scratching. We propose that patients presenting with familial NP be suspect for
      MEN 2A.

PMID- 1362415
TI  - Characterization of the clinical features of five families with hereditary
      primary cutaneous lichen amyloidosis and multiple endocrine neoplasia type 2.
AB  - The hereditary conditions of primary cutaneous lichen amyloidosis and multiple
      endocrine neoplasia type 2 (MEN 2) are rare clinical entities. The initial
      reports of two families in which the two conditions coincided have led to the
      identification of at least eight additional families with this clinical syndrome.
      In this report we describe the clinical features in five of these eight families.
      The salient feature in these five families is the presence of unilateral (46%) or
      bilateral (64%) pruritic and lichenoid skin lesions located over the upper
      portion of the back. Family members describe these skin lesions as intermittently
      intensely pruritic leading to scratching and excoriation of the upper back
      region. The presence of MEN 2 has been documented in 97% of family members with
      this skin lesion, the one exception being a child who is at risk for development
      of MEN 2A in whom the diagnosis has not yet been made. Of family members who have
      MEN 2A, 27% do not have an identifiable skin lesion, although the skin lesion
      developed in one patient two years after a curative thyroidectomy for medullary
      thyroid carcinoma (MTC). Four of the five families have members with
      pheochromocytoma; one with five affected members has only MTC. The finding of
      this clinical syndrome in geographically diverse portions of the world and the
      lack of overlap with MEN 2A without the skin lesion suggest it is a distinct
      clinical variant of MEN 2A.

PMID- 1362416
TI  - Unusual features of multiple endocrine neoplasia.
AB  - In addition to the common presentations of the multiple endocrine neoplasia (MEN)
      syndromes, unusual organ involvement as rare manifestations of a single disease
      may occur. Among our patients we have identified four cases in which unusual
      features of MEN were present. In the first patient, bilateral adrenal cortical
      adenoma, parathyroid adenoma, multiple pancreatic tumors, and follicular thyroid
      carcinoma were observed. The second patient suffered from thymic carcinoid,
      parathyroid hyperplasia, gastrinoma, and pituitary adenoma. Additionally, one
      family was discovered in which medullary thyroid carcinoma (MTC), Hirschsprung's
      disease, and pheochromocytoma occurred and another family had MTC and ovarian
      cancer. Based on these observations, we stress the importance of screening for
      MEN syndromes in all patients with pathologic findings in any endocrine organ.

PMID- 1362417
TI  - Long-term follow-up in four large MEN 2 families in The Netherlands.
AB  - Results of follow-up studies in four large multiple endocrine neoplasia type 2A
      families (total of 95 patients affected) have shown a positive effect on the
      course of the disease since early screening and intervention were initiated in
      1974.

PMID- 1362418
TI  - Mineral metabolic effects of thyroidectomy and long-term outcomes in a family
      with MEN 2A.
AB  - We have followed a family with multiple endocrine neoplasia type 2A for 18 years.
      Four members have undergone total thyroidectomy for medullary thyroid carcinoma
      or C-cell hyperplasia, and one has required bilateral adrenalectomy for
      pheochromocytoma. None has developed hypercalcemic hyperparathyroidism, although
      parathyroid hormone levels were relatively high prethyroidectomy and fell
      postoperatively in the patients with high calcitonin levels. In three of the four
      cases, intestinal calcium absorption decreased following thyroidectomy.

PMID- 1362419
TI  - Statistical analysis of histomorphological findings in medullary thyroid
      carcinoma: distinction between the different familial forms of the disease.
      G.E.T.C. Groupe d'Etude des Tumeurs a Calcitonine.
AB  - A multifactorial analysis of morphological findings was performed on 153 cases of
      medullary thyroid carcinoma (MTC). The aim of the study was to utilize
      histological criteria to discriminate between MTC associated with multiple
      endocrine neoplasia type 2A (MEN 2A) and that associated with the inherited MTC
      only syndrome. The presence of fusiform cells associated with several other
      markers seemed to be more predictive of MEN 2A. A comparison of inherited MTC
      only and sporadic MTC only showed fusiform cells to be significantly less common
      in inherited MTC only. These results suggest that the inherited MTC only syndrome
      is a distinct clinical and morphological entity. Further investigations are
      needed to confirm the findings and understand its implications.

PMID- 1362421
TI  - Microsurgical lymph node dissection for metastatic asymptomatic C-cell carcinoma.
AB  - In persistent, clinically inapparent medullary thyroid carcinoma, microsurgical
      dissection of all lymph node compartments of the neck was performed. Between
      August 1988 and September 1991, 28 cases (mean age 43.3 years) were treated with
      38 surgical interventions. Twenty patients had the sporadic form and eight
      patients the familial form. Unilateral neck dissection resulted in normalization
      of serum calcitonin (CT) levels even after pentagastrin stimulation in two
      patients whereas 16 patients exhibited abnormal CT stimulation tests. Eight of
      ten patients who had bilateral neck dissections had positive pentagastrin test
      results after surgery. The main postoperative complications included loss of
      local cutaneous sensation, generally temporary, and unilateral recurrent
      laryngeal nerve paralysis.

PMID- 1362420
TI  - Frequency and significance of cervicomediastinal lymph node metastases in
      medullary thyroid carcinoma: results of a compartment-oriented microdissection
      method.
AB  - The frequency and significance of cervicomediastinal lymph node metastases have
      been investigated in 82 medullary thyroid carcinoma (MTC) patients
      retrospectively comparing two surgical techniques of lymph node dissection:
      selective lymphadenectomy (n = 63) versus compartment-oriented microdissection (n
      = 35). No positive correlation was observed between primary tumor size and the
      number of lymph node metastases. In patients with lymph node metastases proven
      histologically, 42% showed only cervical involvement (35% unilateral--type A, 7%
      bilateral--type B) and 22% cervicomediastinal lymph node involvement (15% cervico
      unilateral and mediastinal--type C, 7% cervicobilateral and mediastinal--type D).
      Biochemical cure was 83% in node-negative patients but only 21% in node-positive
      patients. In node-positive MTC, calcitonin normalization was achieved in none
      with bilateral lymph node involvement but only in those unilateral lymph node
      metastases (31% in type A, 17% in type C). Survival and biochemical cure are
      significantly improved by application of the compartment-oriented microdissection
      method more so at primary surgery than at reoperation.

PMID- 1362422
TI  - Pheochromocytoma: a frequent indicator for MEN 2.
AB  - Pheochromocytoma is a frequent indicator of multiple endocrine neoplasia type 2A
      (MEN 2A); in the 35 French MEN 2A families in which a pheochromocytoma occurred
      first in some affected members, 30% of the patients had a pheochromocytoma as the
      first manifestation constituting 45% of all patients with pheochromocytomas. The
      finding of a pheochromocytoma is a strong indication for a search for medullary
      thyroid carcinoma and for initiating family screening.

PMID- 1362423
TI  - Surgical approach of synchronous medullary thyroid carcinoma and pheochromocytoma
      in MEN 2 syndrome.
AB  - In cases with concurrent medullary thyroid carcinoma (MTC) and pheochromocytoma,
      discussion regarding a one-stage versus two-stage treatment strategy approach
      remains open. From 1975 to 1990, 11 of 25 multiple endocrine neoplasia type 2
      (MEN 2) patients presented with biendocrinopathies or triendocrinopathies
      synchronously. All patients were treated surgically and followed subsequently in
      our hospital. Of the group of nine patients with concurrent MTC and
      pheochromocytoma, five were treated in one-stage and four in two-stage
      procedures. No patient had major complications intraoperatively. For the two
      stage group, the total hospital stay (preoperatively and postoperatively)
      averaged 35 days. For the one-stage group, the total hospital stay averaged 25
      days. In patients with increased operative risks (patients with higher age and
      impaired physical condition or if neck surgery includes transsternal
      cervicomediastinal lymphadenectomy), two-stage procedures should be selected.
      However, in young patients with the MEN 2 syndrome or syndromes with small tumors
      detected by family screening, thyroidectomy, cervical lymphadenectomy, and
      adrenalectomy may be performed in a one-stage procedure without increasing
      surgically related morbidity.

PMID- 1362424
TI  - Evaluation of children with medullary thyroid carcinoma.
AB  - Early diagnosis and surgical treatment of medullary thyroid carcinoma (MTC) in
      children is essential to decrease the likelihood of metastatic spread. From 1981
      to 1991, eight children under 18 years of age (five girls and three boys) with
      MTC were seen and seven underwent total thyroidectomy. Follow-up ranged from 14
      months to 10 years after surgery. Four of the seven presented with a neck mass
      and elevated basal levels of calcitonin (CT). After surgery, three had recurrent
      disease. In the other three, the diagnosis was made after several years of
      screening (normal basal values of CT but increased CT levels after
      calcium/pentagastrin infusion). All had normal stimulated CT values
      postoperatively. This follow-up showed that the prognosis for MTC in children
      depends predominantly upon its extent at the time of the diagnosis and treatment.

PMID- 1362425
TI  - Oncogene and growth factor expression in MEN 2 and related tumors.
AB  - Pheochromocytomas occur sporadically or in individuals affected by inherited
      syndromes including multiple endocrine neoplasia (MEN) type 2A and 2B,
      neurofibromatosis, and the von Hippel-Lindau syndrome (vHL). Medullary thyroid
      carcinomas (MTCs) also occur sporadically or as part of MEN 2A, MEN 2B, and
      familial MTC. Little is known of the molecular genetic background of these
      tumors. We have shown previously that activation of the N-ras, H-ras, and K-ras
      oncogenes does not occur in these tumors, but that deletions of the short arm of
      chromosome 1 are extremely common (> 60%) and may indicate loss of a suppressor
      gene in the chromosomal region 1p31-36. We have examined the structure and
      expression of N-myc, c-myc, L-myc, c-mos, nerve growth factor (beta-NGF), and the
      low affinity nerve growth factor receptor (LNGFR) in a series of
      pheochromocytomas and MTCs from patients with hereditary and sporadic diseases.
      Southern analysis, using radiolabeled DNA probes, revealed no evidence of
      amplification or rearrangement of these genes in any normal or tumor tissues
      except for loss of heterozygosity at the L-myc locus (1p32) in 9
      pheochromocytomas from patients with MEN 2A or MEN 2B, in 5 of 11 non-MEN
      pheochromocytomas, and in 3 of 24 non-MEN MTCs. Gene expression at the RNA level
      was examined by Northern analysis or ribonuclease protection assay (RPA) using
      radiolabeled DNA or cRNA probes. C-myc transcripts were detectable at low levels
      in all tumors tested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362426
TI  - Somatostatin acts via a pertussis toxin-sensitive mechanism on calcitonin
      secretion in C-cells.
AB  - The effect of the somatostatin analog octreotide on cAMP-mediated calcitonin (CT)
      secretion and cAMP accumulation in C-cells was investigated. Glucagon stimulated
      cAMP accumulation and CT secretion with a maximal effect at a concentration of
      10(-6) M. The cAMP antagonist RpcAMPs blocked the glucagon-induced CT secretion
      down to control levels. Therefore, no other second messengers seem to be involved
      in glucagon-stimulated CT secretion. Octreotide in increasing doses (10(-9) to
      10(-6) M) inhibited cAMP accumulation and CT secretion with a maximal effect at a
      concentration of 10(-7) (40% and 29% of control values, respectively).
      Pretreatment of the cells with 100 ng/mL pertussis toxin for 24 hours abolished
      the inhibitory effect of octreotide on cAMP accumulation and CT secretion (82%
      and 58% of control values, respectively). Similar results were obtained under the
      influence of the phosphodiesterase inhibitor IBMX. Therefore, we conclude that
      somatostatin modulates adenylate cyclase-coupled CT secretion in C-cells via a
      pertussis toxin-sensitive G-protein possibly in an autocrine/paracrine way.

PMID- 1362427
TI  - Patterns of neoplasia in c-mos transgenic mice and their relevance to multiple
      endocrine neoplasia.
AB  - We have previously described a neurological phenotype for transgenic mice
      carrying the c-Mos proto-oncogene. Pheochromocytomas and C-cell thyroid neoplasms
      occur in these transgenic lines in patterns that are similar to those seen in
      multiple endocrine neoplasia type 2 (MEN 2). Characterization of the pathological
      lesions via immunohistochemistry underscores similarities between MEN 2 and these
      transgenic mice. When transgenic mice that do not display the MEN 2 phenotype are
      crossed to a different background, the progeny display the MEN 2 phenotype. Thus
      the interaction of the background with the transgene is such that it can suppress
      tumor information. This observation bears special relevance to the human syndrome
      in that this model system may be used to study the question of penetrance of
      phenotype.

PMID- 1362428
TI  - Enhancement by monocytes of perforin production and its gene expression by human
      CD8+ T cells stimulated with interleukin-2.
AB  - Pore-forming protein (PFP) is an important effector molecule for cytotoxicity
      mediated by cytotoxic T cells and NK cells. In the present study, the effect of
      monocytes on PFP production by interleukin-2 (IL-2)-stimulated T lymphocytes was
      examined. Highly purified lymphocytes (> 99%) and monocytes (> 90%) were isolated
      by centrifugal elutriation from peripheral blood of healthy donors, and, CD4+ and
      CD8+ cells were isolated from the purified lymphocytes by using antibody-bound
      magnetic beads. PFP production was quantitated with a universal
      microspectrophotometer in combination with immunostaining using anti-PFP
      antibody. Monocytes did not produce any PFP. High levels of PFP production were
      observed in CD8+ cells, but not CD4+ cells after incubation for 4 days with IL-2.
      Addition of monocytes to cultures of CD8+ cells resulted in significant
      augmentation of PFP production after 3 days' stimulation with IL-2. Monokines
      (TNF alpha and IL-6) caused a significant increase in PFP production by IL-2
      stimulated CD8+ cells. Northern blot analysis revealed that the PFP mRNA levels
      was enhanced by stimulation with IL-2, and that addition of monocytes to cultures
      of CD8+ cells plus IL-2 augmented their PFP mRNA expression. These observations
      suggest that monocytes are important in in situ regulation of the CD8+ T cell
      mediated cytotoxic response through production of PFP.

PMID- 1362429
TI  - Immunohistochemical localization of hepatocyte growth factor protein in pancreas
      islet A-cells of man and rats.
AB  - Hepatocyte growth factor (HGF), a potent mitogen for adult rat hepatocytes in
      primary culture, has previously been shown to be primarily expressed in the
      nonparenchymal cells of the liver. Using polyclonal antisera against human and
      rat HGFs we studied the tissue distribution of HGF immunohistochemically and
      found the most intense staining in the pancreas islet cells in both man (autopsy
      cases) and the rat. Differential localization of 4 pancreas islet hormones,
      glucagon, insulin, somatostatin and pancreatic polypeptide, revealed HGF to be
      preferentially expressed within the glucagon-positive cells. The results indicate
      that HGF is primarily produced or stored in A-cells and may act as a growth
      factor in a paracrine and an endocrine fashion, like various other hormones.

PMID- 1362431
TI  - Direct observations of synapses between L-glutamate-immunoreactive boutons and
      identified spinocervical tract neurones in the spinal cord of the cat.
AB  - Four spinocervical tract cells in lumbosacral spinal cords of adult cats were
      physiologically characterized and intracellularly labelled with horseradish
      peroxidase. The neurones were examined with a light microscope and reconstructed.
      Selected regions were chosen for ultrastructural analysis. Thin sections were
      treated to reveal the presence of L-glutamate by using the postembedding
      immunogold method. Two antisera, which specifically recognise the presence of
      fixed glutamate in tissue, were used in the study. Somata, proximal, and distal
      dendrites of all four neurones received synaptic contacts from boutons which
      displayed an obvious immunogold reaction. These boutons formed between 35% and
      48% of all synaptic contacts onto spinocervical tract cells. Glutamate-enriched
      boutons were associated with gold particle densities which were 2-3 times greater
      than the average densities associated with the surrounding neuropil. Their
      profiles had a mean diameter of 1.68 microns, contained round agranular synaptic
      vesicles, and formed asymmetrical synaptic junctions. However, not all boutons
      displaying these characteristics were enriched with glutamate. Immunogold studies
      of alternate thin sections, which were incubated with glutamate or GABA
      antiserum, demonstrated that synaptic boutons on spinocervical tract cells were
      either enriched with GABA or with glutamate and formed two separate populations
      which had distinct morphological characteristics. GABA-containing boutons
      contained irregularly shaped agranular vesicles and formed symmetrical synaptic
      junctions, whereas glutamate-enriched boutons corresponded to those described
      above. A further population of boutons, containing highly flattened vesicles, was
      not immunoreactive for GABA or glutamate. The evidence supports the idea that
      much of the excitatory transmission into the SCT is mediated by L-glutamate.

PMID- 1362432
TI  - A prospective randomised controlled trial comparing the efficacy of somatostatin
      with injection sclerotherapy in the control of bleeding oesophageal varices.
AB  - Since previous reports have suggested that somatostatin may be of value in the
      control of acute variceal haemorrhage, we compared its efficacy with that of
      injection sclerotherapy in a randomised controlled clinical trial. Eighty
      consecutive patients with endoscopically-proven severe variceal bleeding were
      randomised to injection sclerotherapy (n = 41) or somatostatin (n = 39) given as
      a continuous infusion of 250 micrograms/h for 5 days plus daily bolus
      administration of 250 micrograms. The efficacy of injection sclerotherapy and
      somatostatin infusion in controlling haemorrhage and preventing rebleeding
      (censored at 5 days), mortality (censored at 28 days) and complications was
      compared. The aetiology of the portal hypertension and transfusion requirements
      was similar between the two groups, but there were more patients with severe
      liver disease (Child's C) in the somatostatin group. There was no significant
      difference between the two treatments in the initial (p = 1.0) or overall control
      of bleeding (p = 0.58). Furthermore, somatostatin was as effective as injection
      sclerotherapy in controlling bleeding in patients with severe liver disease or in
      those actively bleeding at the time of their endoscopy. The relative risk of
      rebleeding whilst receiving somatostatin compared to injection sclerotherapy was
      1.39 [95% Confidence Interval (CI) 3.73; 0.52], but this was reduced to 0.98 (95%
      CI 0.37; 2.67) when readjusted for Child's grading, the only prognostic factor
      shown to be of significance. Mortality was not significantly different between
      the two groups of patients (p = 0.31). The relative risk of dying whilst
      receiving somatostatin compared to injection sclerotherapy was 1.6 (95% CI 3.93;
      0.66) but was reduced to 1.03 (95% CI 0.47; 2.47) when adjusted for Child's
      grading, the only significant prognostic factor. Complications in the
      somatostatin group were minor and less frequent than after injection
      sclerotherapy. The results of this study indicate that somatostatin is a safe
      treatment, which is as effective an endoscopic injection sclerotherapy for acute
      variceal bleeding.

PMID- 1362430
TI  - Topography and collateralization of the dopaminergic projections to motor and
      lateral prefrontal cortex in owl monkeys.
AB  - The sources and histochemical characteristics of dopaminergic projections to
      motor and premotor areas of cortex were investigated in owl monkeys in which
      information from related studies was used to subdivide cortex into motor fields.
      Brainstem projections to frontal cortex were identified by injections of
      different fluorescent dyes in the primary motor cortex (M1) and the supplementary
      motor area (SMA), first identified by microstimulation. Injections were also
      placed in dorsal premotor cortex and lateral prefrontal cortex. The distribution
      of retrogradely labeled neurons was related to the location of tyrosine
      hydroxylase immunolabeled neurons on the same or alternate brain sections to
      identify the dopamine (DA) neurons. All DA cortically projecting neurons were
      located in the A8-A10 complex, largely in its dorsal components, including the
      parabrachial pigmented n. of the ventral tegmental area (VTA), pars gamma of the
      substantia nigra compacta, and the dorsal part of the retrorubral area (A8).
      Fewer cells were in the midline groups of VTA (n. linearis rostralis and
      caudalis) and in the n. paranigralis. DA neurons projecting to M1, SMA, and
      prefrontal cortex were largely intermixed, and some of these neurons were double
      or triple labeled by the fluorescent dyes, indicating collateralization to two or
      three fields; DA cells projecting to M1 were more numerous than to the other
      locations. The dorsal components of the A8-A10 complex from which arose the DA
      mesocortical projection were also characterized by the presence of calbindin
      immunoreactive neurons and by a dense neurotensin and noradrenergic terminal
      innervation. Compared to rodents or felines, the DA neurons projecting to the
      lateral frontal lobe of primates appear to be shifted dorsally and laterally in
      the nigral complex. The topographic overlap, partial collateralization, and
      common histochemical characteristics of the DA mesocortical neurons projecting to
      different fields of the lateral frontal lobe suggest that some degree of
      functional unity exists within this projection.

PMID- 1362433
TI  - Kinetic analysis of hepatobiliary transport of vincristine in perfused rat liver.
      Possible roles of P-glycoprotein in biliary excretion of vincristine.
AB  - Recent studies using bile canalicular membrane vesicles have suggested that P
      glycoprotein may play a role in excreting some anticancer drugs from the liver to
      the bile. At steady state after a continuous single-pass perfusion of a tracer
      concentration of [3H]vincristine in the rat liver, the extraction ratio was
      approximately 0.6, and 70% of the extracted drug was excreted into the bile
      mostly in unchanged form. The liver/perfusate and bile/liver unbound
      concentration ratios obtained after correction for intracellular binding and the
      inside-negative membrane potentials and/or pH difference between the inside and
      outside of the cells, were approximately 2-3 and 160-280, respectively,
      suggesting a highly concentrated biliary excretion process. We also examined the
      effects of verapamil, a P-glycoprotein-related transport inhibitor in cancer
      cells, on the hepatobiliary transport of [3H]vincristine. Verapamil 50 microM in
      the perfusate caused a decrease in the biliary excretion rate of [3H]vincristine,
      whereas [14C]taurocholate (reference compound) remained constant. In contrast,
      the hepatic uptake rate of [3H]vincristine exhibited minimum reduction,
      suggesting that verapamil selectively inhibited the biliary excretion of
      [3H]vincristine at the canalicular membrane. The fact that verapamil had little
      effect on the initial velocity of [3H]vincristine uptake by isolated hepatocytes
      also supports the above findings. Since the effect of 150 microM verapamil in the
      perfusate was not selective for vincristine, the biliary excretion rates of both
      compounds ([3H]vincristine, [14C]taurocholate) were reduced by this concentration
      of verapamil. In conclusion, the concentrative excretion of vincristine into the
      bile and its selective inhibition by a moderate concentration of verapamil
      provide indirect evidence for the contribution of P-glycoprotein to the biliary
      excretion of vincristine in a perfused rat liver system.

PMID- 1362434
TI  - Depressed inotropic response to beta-adrenoceptor agonists in the presence of
      advanced cardiac hypertrophy in hearts from rats with induced aortic stenosis and
      from spontaneously hypertensive rats.
AB  - OBJECTIVE: To study the inotropic response to beta-adrenoceptor stimulation in
      isolated hypertrophied hearts from hypertensive rats. DESIGN AND METHODS: Cardiac
      hypertrophy was induced in Wistar rats by stenosing the abdominal aorta.
      Functional responses to isoprenaline, dobutamine, terbutaline and salbutamol were
      measured in paced (5 Hz), aortically stenosed hearts (18-20 and 32-34 weeks of
      age) and compared with those of sham-operated spontaneously hypertensive (SHR)
      and Wistar-Kyoto (WKY) rats. RESULTS: Following aortic stenosis, which was
      accompanied by less hypertension than that sustained by SHR, the Wistar rat
      hearts showed more pronounced cardiac hypertrophy. An initially equal inotropic
      response to the beta-adrenoceptor agonists (18-20 weeks) was reduced to 45% at 32
      34 weeks in SHR but not in WKY rat hearts. The response to beta-adrenoceptor
      stimulation in the hypertrophied Wistar rat hearts was reduced at 18-20 weeks to
      30% and at 32-34 weeks to 10% of controls, respectively. The response by all
      hypertrophied hearts to forskolin and N,2'-O-dibutyryladenosine 3':5'
      monophosphate was also diminished. CONCLUSIONS: The impaired contractile response
      to beta-adrenoceptor agonism is more clearly related to cardiac hypertrophy than
      to hypertension.

PMID- 1362435
TI  - [Functional roles of synaptotagmin in neurotransmitter release].

PMID- 1362436
TI  - Effects of the association of alpha and beta-blocking agents in glaucoma.
AB  - Twenty patients with POAG and early visual field changes, already under treatment
      with 0.5% timolol were randomly assigned to additional topical treatment with
      0.5% dapiprazole or placebo. After six months of treatment no differences were
      observed between the groups for what concerns visual field. After six months of
      treatment visual field, visual flicker discrimination and contrast sensitivity
      proved to be constant without differences between the groups. On the contrary,
      mean IOP was found to be significantly lower in the dapiprazole group.

PMID- 1362437
TI  - An efficient statistical procedure for interpreting DNA single locus profiling
      data in crime cases.
AB  - This paper describes a simplified approach to calculating the Bayesian likelihood
      ratio for the case where two DNA single locus profiles are to be compared. It
      explains how the calculation allows for band shift and also for the variation in
      precision with molecular weight. A simple basic theory section explains the
      principles of the analysis but more detailed explanations are given in an
      advanced theory section. Experiments on substantial data collections are
      described which demonstrate the robustness of the method.

PMID- 1362438
TI  - The inflammatory myelinopathy of adreno-leukodystrophy: cells, effector
      molecules, and pathogenetic implications.
AB  - Prominent inflammation in the demyelinative lesion of adreno-leukodystrophy (ALD)
      has suggested an immune-mediated pathogenetic component. Commercially available
      antibodies to T cells, B cells, macrophages, class I and II molecules,
      complement, IgG, IgM, IgA, interleukin-1 (IL-1), intercellular adhesion molecule
      1 (ICAM-1) and tumor necrosis factor-alpha (TNF) were applied to paraffin
      sections of formaldehyde-fixed postmortem samples. Twenty-five primary
      demyelinative lesions from five juvenile ALD, three adult ALD, and three
      adrenomyeloneuropathic patients were evaluated with appropriate positive and
      negative controls. Macrophages and astrocytes were the predominant cells detected
      at the active edge; T lymphocytes, including T4 and CD45R subsets, were nearly as
      numerous but usually located around vessels within the lesion. B cells and plasma
      cells, usually containing IgG, were uncommon. The expression of class II
      molecules, restricted to one adult, was problematic; class I expression was
      increased in microvascular and other cells. Degraded myelin was labeled with
      antibodies to C3d and IL-1; IL-1 and ICAM-1 immunoreactivity was seen on
      microvessels and astrocytes. Tumor necrosis factor-alpha immunoreactivity was
      detected in macrophages, but more prominently in astrocytes. These data support a
      natural immune response in the demyelinative lesion of ALD, consisting
      predominantly of reactive astrocytes, macrophages, T cells and cytokines. A two
      stage pathogenetic theory is discussed. The postulated roles of TNF and reactive
      astrocytes, in concert with a fundamental myelinolytic biochemical defect,
      suggest a different pathogenetic mechanism and raise novel therapeutic
      possibilities.

PMID- 1362439
TI  - Current diagnostic concepts of astrocytic tumors.

PMID- 1362440
TI  - PrP protein is associated with follicular dendritic cells of spleens and lymph
      nodes in uninfected and scrapie-infected mice.
AB  - Abnormal forms of a host protein, PrP, accumulate in the central nervous system
      in scrapie-affected animals. Here, PrP protein was detected immunocytochemically
      in tissue sections of spleen, lymph node, Peyer's patches, thymus, and pancreas
      from uninfected mice and from mice infected with a range of mouse-passaged
      scrapie strains and bovine spongiform encephalopathy (BSE). In the spleen, lymph
      node and Peyer's patches, PrP-positive cells were identified as follicular
      dendritic cells (FDC) by their location, appearance, and immune complex trapping
      function, whereas in the thymus they appeared to be two types of stromal cells:
      interdigitating cells (IDC) and cortical epithelial cells. In pancreas, PrP
      containing cells were confined to the islets of Langerhans. Although the
      distribution of PrP immunolabelling was the same in tissues from scrapie-affected
      and uninfected mice, there was evidence that PrP accumulated in abnormal forms in
      FDC of infected mice. If, as is likely, PrP is essential for agent replication,
      our results suggest that FDC are the site of scrapie and BSE replication in the
      spleen and lymph node.

PMID- 1362441
TI  - Activation of the central pattern generators for locomotion by serotonin and
      excitatory amino acids in neonatal rat.
AB  - 1. The role of serotonin (5-HT) and excitatory amino-acids (EAAs) in the
      activation of the neural networks (i.e. the central pattern generators) that
      organize locomotion in mammals was investigated in an isolated brainstem-spinal
      cord preparation from the newborn rat. 2. The neuroactive substances were bath
      applied and the activity of fictive locomotion was recorded in the ventral roots.
      3. Serotonin initiated an alternating pattern of right and left action potential
      bursts. The period of this rhythm was dose dependent, i.e. it decreased from
      around 10 s at 2 x 10(-5) M to 5 s at 10(-4) M. The effects of serotonin were
      blocked by a 5-HT1 antagonist (propranolol) and by 5-HT2 antagonists (ketanserin,
      cyproheptadine, mianserin). 5-HT3 antagonists were ineffective. The effects of
      methoxytryptamine, a non-selective 5-HT agonist, mimicked the 5-HT effects. 4.
      The endogenous EAAs, glutamate and aspartate, also triggered an alternating
      rhythmic pattern. Their effects were blocked by 2-amino-5-phosphonovaleric acid
      (AP-5; a N-methyl-D-aspartate (NMDA) receptor blocker) and 6,7-dinitro
      quinoxaline-2,3-dione (a non-NMDA receptor blocker). 5. Several EAA agonists (N
      methyl-D,L-aspartate (NMA) and kainate) initiated rhythmic activity. The period
      of the induced rhythm (from 3 to 1 s) was similar with both of these substances
      but in a range of concentrations which was ten times lower in the case of kainate
      (10(-6) to 5 x 10(-6) M) than in that of NMA (10(-5) to 4 x 10(-5) M). alpha
      Amino-3-hydroxy-5-methylisoxazole-4-propionate and quisqualate occasionally
      triggered some episodes of fictive locomotion with a threshold at 6 x 10(-7) and
      10(-5) M, respectively.

PMID- 1362442
TI  - Properties of supraoptic magnocellular neurones isolated from the adult rat.
AB  - 1. Magnocellular neurosecretory cells (MNCs) were isolated from the supraoptic
      nucleus of adult Long-Evans rats using an enzymatic procedure. Immunocytochemical
      staining with antibodies against vasopressin and oxytocin revealed that MNCs can
      be identified by size. The membrane properties of these cells were examined at 32
      34 degrees C using intracellular recording methods. 2. Isolated MNCs displayed a
      mean (+/- S.E.M.; n = 109) resting membrane potential of -64.1 +/- 1.0 mV, an
      input resistance of 571 +/- 34 M omega, and a time constant of 8.7 +/- 0.4 ms.
      Measurements of specific resistivity and input capacitance revealed that the soma
      of these cells accounts for a mere 20% of their total somato-dendritic membrane
      in situ. 3. Voltage-current relations measured near -60 mV were linear negative
      to spike threshold. From more hyperpolarized membrane potentials, voltage
      responses to depolarizing current steps displayed transient outward rectification
      and delayed impulse discharge. 4. Action potentials (76.6 +/- 0.9 mV) triggered
      from an apparent threshold of -59.3 +/- 0.1 mV broadened progressively at the
      onset of spontaneous or current-evoked spike trains. Steady-state spike duration
      increased as a logarithmic function of firing frequency with a maximum near 25
      Hz. These effects were abolished in Ca(2+)-free solutions. 5. In all cells,
      evoked spike trains were followed by a prolonged Ca(2+)-sensitive after
      hyperpolarization. In contrast, only a small proportion (16%) of MNCs displayed
      spontaneous bursting activity or depolarizing after-potentials following brief
      current-evoked bursts. 6. Isolated MNCs responded to amino acids (glutamate and
      GABA) and to the neuropeptide cholecystokinin, indicating that receptors for
      these neurotransmitters are expressed postsynaptically by MNCs and are retained
      following dissociation. 7. Increasing the osmolality of the superfusing solution
      by 5-30 mosmol kg-1 caused a membrane depolarization associated with a decrease
      of input resistance and accelerated spontaneous spike discharge in each of thirty
      six MNCs tested. Current-clamp analysis suggested that these responses resulted
      from the activation of a cationic conductance. Excitatory effects of
      hyperosmolality were not observed in non-magnocellular neurones (n = 6).

PMID- 1362443
TI  - Transduction mechanism for glutamate-induced potassium current in neurones of the
      mollusc Planorbarius corneus.
AB  - 1. The potassium currents evoked by glutamate agonists on isolated and identified
      neurones of molluscan pedal ganglia were investigated using the voltage clamp
      technique. 2. Glutamate responses were not modified by increasing intracellular
      cyclic nucleotide concentrations (treatment with 8-Br-cAMP, 8-Br-cGMP, forskolin
      and/or the phosphodiesterase inhibitor isobutylmethylxantine, IBMX), whereas
      inward-going currents induced by the nucleotides were observed. It follows that
      glutamate currents are independent of intracellular cyclic nucleotide control. 3.
      Protein kinase C activation with phorbol esters or oleoylacetylglycerol induced a
      slowly developing outward current and reduced glutamate response amplitude.
      Staurosporine itself did not affect the glutamate responses but completely
      prevented the effects of phorbol esters and oleoylacetylglycerol. This indicated
      that protein kinase C was not involved in the transduction mechanism for the
      potassium component of the glutamate response. 4. The possible involvement of
      inositol-1,4,5-trisphosphate seems to be improbable because the glutamate
      responses were independent of intracellular calcium concentration. Intracellular
      injection of calcium buffer BAPTA, failed to affect any of the glutamate
      currents, although it effectively blocked the after-hyperpolarization following
      directly evoked action potentials. 5. Nordihydroguaiaretic acid (NDGA) and
      indomethacin, inhibitors of the lipoxygenase and cyclo-oxygenase pathways of
      arachidonic acid metabolism, correspondingly, did not change the glutamate
      responses of these neurones. 6. The failure to demonstrate the involvement of any
      known secondary messenger systems in glutamate response transduction favours two
      assumptions: (1) the receptor-G protein complex controls the potassium channel
      directly; or (2) some still unknown transduction system is used.

PMID- 1362444
TI  - Electrophysiological studies of anion secretion in cultured human epididymal
      cells.
AB  - 1. Primary monolayer cultures from adult human epididymis were grown on Petri
      dishes and previous supports. The epithelia so formed were used for whole-cell
      patch clamp recording and short-circuit current (ISC) measurement. 2. After 50
      days of culture, the cells formed a tight epithelium with transepithelial
      potential of 5.5 +/- 1.3 mV (mean +/- S.E.M.., n = 16), apical side negative, and
      a basal ISC of 6.9 +/- 0.9 microA cm-2 (mean +/- S.E.M., n = 16). 3. Adrenaline,
      when added to the basolateral side, at a concentration of 0.23 mumol l-1
      increased the ISC by 3.0 +/- 1.2 microA cm-2 (mean +/- S.E.M., n = 4). This
      increase was blockable by diphenylamine-2-carboxylate (DPC, 1 mmol l-1).
      Forskolin (10 mumol l-1) also evoked a similar response to adrenaline. 4. In
      whole-cell patch clamp experiment, the resting membrane potential of the cells
      after dialysis with pipette solution containing 135 mmol l-1 KCl was found to be 
      30 +/- 14 mV (mean +/- S.E.M., n = 15). 5. About 90% of the cells successfully
      forming patches responded to 1 mumol l-1 adrenaline by an increase in inward
      current at -70 mV holding potential (delta I = -1600 +/- 900 pA, mean +/- S.E.M.,
      n = 15). This increase in current was accompanied by a shift in reversal
      potential to -2 +/- 1 mV (mean +/- S.E.M., n = 15). 6. The adrenaline-induced
      inward current was found to be blockable by the Cl- channel blocker, DPC (0.25
      mmol l-1). Ion substitution experiments showed that the adrenaline-evoked current
      was carried mainly by Cl-. 7. The effect of adrenaline on the whole-cell current
      was found to be mimicked by forskolin and could be abolished by including GDP
      beta S or a protein kinase A inhibitor in the pipette solution. Propranolol, but
      not phentolamine, completely abolished the effect of adrenaline. 8. Inclusion of
      20 mmol l-1 EGTA or 2 mmol l-1 BAPTA + 100 mumol l-1 TMB-8 (to inhibit
      intracellular Ca2+ release) in the pipette did not seem to have any marked effect
      on adrenaline-evoked whole-cell current. Lowering the pipette Ca2+ concentration
      to 1 nmol l-1 or raising it to 10 mumol l-1 had no effect on the whole-cell
      current response to adrenaline. 9. This study shows that adrenaline stimulates Cl
      secretion in cultured human epididymal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1362445
TI  - Hepatic encephalopathy. Current concepts of the pathogenesis.
AB  - Hepatic encephalopathy occurs in a number of different species as a result of
      either congenital portacaval shunts or acquired liver disease. Despite intensive
      research, the neurochemical basis of the disorder has not been defined. Theories
      to explain the cerebral dysfunction that accompanies acute or chronic hepatic
      failure include 1) ammonia acting as the putative neurotoxin, 2) perturbed
      monoamine neurotransmission as a result of altered plasma amino acid metabolism,
      3) an imbalance between excitatory amino acid neurotransmission, mediated by
      glutamate, and inhibitory amino acid neurotransmission, mediated by gamma
      aminobutyric acid, and 4) increased cerebral concentrations of an endogenous
      benzodiazepine-like substance.

PMID- 1362446
TI  - A plasmid-encoded type IV fimbrial gene of enteropathogenic Escherichia coli
      associated with localized adherence.
AB  - Enteropathogenic Escherichia coli (EPEC) form adherent microcolonies on the
      surface of tissue culture cells in a pattern termed localized adherence.
      Localized adherence requires the presence of a large EPEC adherence factor (EAF)
      plasmid. Recently a bundle-forming pilus has been described in EPEC possessing
      the EAF plasmid. An analysis of 22 non-invasive EPEC TnphoA mutants revealed that
      seven have insertions in the EAF plasmid and are incapable of localized
      adherence. We report here the mapping of the TnphoA insertions in these mutants.
      The nucleotide sequence of the gene interrupted in these TnphoA mutants (bfpA)
      was determined and found to correspond to the N-terminal amino acid sequence of
      the major structural protein of the bundle-forming pilus. The bfpA gene bears
      sequence similarities to members of the type IV fimbrial gene family and encodes
      a potential site for processing by a prepilin peptidase. A plasmid containing
      bfpA as the only open reading frame directs the synthesis of a protein recognized
      by antiserum raised against the bundle-forming pilus. TnphoA mutants at this
      locus are unable to synthesize BfpA, but synthesis is restored by introduction of
      a plasmid containing the cloned gene. The minimum fragment of DNA required to
      restore localized adherence is considerably greater than that required to restore
      BfpA synthesis. BfpA expression, as assessed by alkaline phosphatase activity in
      bfpA::TnphoA mutants, is affected by temperature and growth medium. These studies
      describe an EPEC plasmid-encoded fimbrial gene, a candidate for the elusive EPEC
      adherence factor responsible for localized adherence.

PMID- 1362447
TI  - Interaction of two variable proteins (PilE and PilC) required for pilus-mediated
      adherence of Neisseria gonorrhoeae to human epithelial cells.
AB  - Pili confer the initial ability of Neisseria gonorrhoeae to bind to epithelial
      cells. Pilin (PilE), the major pilus subunit, and a minor protein termed PilC,
      reportedly essential for pilus biogenesis, undergo intra-strain phase and
      structural variation. We demonstrate here that at least two different adherence
      properties are associated with the gonococcal pili: one is specific for
      erythrocytes, which is virtually unaffected by PilE variation, and another is
      specific for epithelial cells, and is modulated in response to the variation of
      PilE. Based on this finding, mutants of a recA- strain were selected that had
      lost the ability to bind to human cornea epithelial cells (A-) but retained the
      ability to form pili (P+) and to agglutinate human erythrocytes (H+). The
      adherence-negative mutants failed to produce detectable levels of PilC1 or PilC2
      proteins, representing piIC phase variants generated in the absence of RecA. The
      A- pilC phase variants were indistinguishable from their A+ parents and
      spontaneous A+ revertants with regard to the amount of PilE produced and its
      electrophoretic mobility, the degrees of piliation and haemagglutination, and the
      pilE nucleotide sequence. These data demonstrate a central role for PilC in pilus
      mediated adherence of N. gonorrhoeae to human epithelial cells and further
      indicate that neither PilC1 nor PilC2 is obligatory for the assembly of
      gonococcal pili.

PMID- 1362448
TI  - The neurobiochemical involvement of taurine in ocular pathology.

PMID- 1362449
TI  - Cellular interactions in the striatum involving neuronal systems using
      "classical" neurotransmitters: possible functional implications.
AB  - The neostriatum contains a wide variety of neuroactive substances associated with
      several well-defined functional neuronal systems. This structure, which is the
      seat of numerous neurological pathological disorders, is commonly used as a model
      for studying the basic mechanisms of neurotransmitter interactions in the brain
      and their putative involvement in striatal functions. Increasing interest has
      been focusing lately on the cellular interactions that may occur between the
      corticostriatal putatively glutamatergic system and the nigrostriatal
      dopaminergic input. Current evidence suggests that the activatory corticostriatal
      glutamatergic input may play a more crucial role in regulating striatal functions
      than was formerly assumed in comparison with the dopaminergic input. The key role
      of cholinergic interneurons in the striatum may therefore be attributable to the
      fact that they modulate the glutamatergic transmission to GABA striatal efferent
      neurons. Likewise, dopamine may actually act indirectly in the striatum by
      "tuning down" the cortical excitation of striatal neurons. Consequently, an
      impairment of the dopaminergic transmission such as that occurring in
      Parkinsonism may lead to an increase in the corticostriatal glutamatergic
      transmission, which may further contribute towards reinforcing the "imbalance"
      between subsets of striatal neuronal systems controlling the output of the basal
      ganglia.

PMID- 1362450
TI  - Molecular cloning of GRA4, a Toxoplasma gondii dense granule protein, recognized
      by mucosal IgA antibodies.
AB  - Clones which were selected from a Toxoplasma gondii expression library with the
      immune serum from a T. gondii-infected rabbit, were further screened using milk
      and intestinal secretions from mice which had been orally infected with T. gondii
      cysts. The gene products of several clones reacted strongly with milk IgA and
      weakly with intestinal IgA. Three of these clones (5.1, 36.1, 37.4) were shown to
      encode a dense granule protein of 40 kDa (GRA4). The GRA4 protein co-migrates
      with one of the T. gondii antigens recognized by mucosal IgA. The complete
      nucleotide sequence of GRA4 has been obtained by cloning genomic T. gondii BamHI
      fragments containing the 37.4 DNA insert. The coding sequence contains no intron.
      The deduced amino acid sequence indicates a proline rich (12%) product with an
      internal hydrophobic region of 19 amino acids and a potential site of N
      glycosylation. The primary translation product with a theoretical size of 36,260
      Da contains a putative N-terminal signal sequence of 20 amino acids but no
      apparent glycolipid anchor sequence. Quantitation of the GRA4 gene and Southern
      blot analysis suggested that the GRA4 gene is single copy. GRA4 gene is
      translated in tachyzoites to yield a single mRNA species of about 1900 bases.

PMID- 1362451
TI  - Glycosyl phosphatidylinositol-specific phospholipase C of Trypanosoma brucei:
      expression in Escherichia coli.
AB  - Glycosyl phosphatidylinositol-specific phospholipase C (GPI-PLC) from Trypanosoma
      brucei cleaves the glycosyl phosphatidylinositol (GPI) anchor of the trypanosome
      variant surface glycoprotein (VSG) and other GPI structures. We have expressed
      this enzyme in Escherichia coli, using a protocol designed to produce the native
      enzyme rather than a fusion protein. We have purified large amounts of GPI-PLC
      from E. coli membranes, using a single step immunoaffinity technique. The
      expressed enzyme is identical to its trypanosome counterpart in enzymatic
      specificity, mobility on SDS-PAGE, and isoelectric point. Recombinant GPI-PLC is
      a membrane enzyme; it associates with E. coli membranes and, like the T. brucei
      GPI-PLC, partitions into the detergent phase in Triton X-114 phase separation
      experiments. The Michaelis constants for the two enzymes are similar (400 nM,
      with VSG as substrate). The turnover number (kcat, 72 min-1) of the recombinant
      enzyme (expressed from a. T. brucei rhodesiense WRATat 1.1 cDNA) is about one
      tenth that of GPI-PLC from T. brucei brucei (ILTat 1.3).

PMID- 1362453
TI  - Direct demonstration of dopamine D1-like receptor sites in the ciliary body of
      the rabbit eye by light microscope autoradiography.
AB  - The pharmacological characteristics and the anatomical localization of [3H]-SCH
      23390 in sections of the ciliary body of the rabbit eye were analyzed using a
      radioreceptor assay and autoradiographic techniques. [3H]-SCH 23390 was bound to
      sections of rabbit ciliary body in a manner consistent with the labelling of D1
      like receptor sites. The dissociation constant (Kd) was 0.62 nmol/l, while the
      maximum binding capacity (Bmax) was 117 +/- 9 fmol/mg tissue. Light microscope
      autoradiography revealed [3H]-SCH 23390 binding sites within the epithelium of
      the ciliary processes, which is the ocular structure involved in the secretion of
      aqueous humor. No specific accumulation of silver grains was noticeable within
      the iridocorneal angle, which is the structure involved in the outflow of aqueous
      humor. These findings suggest that the rise in intraocular pressure caused by D1
      receptor agonists is probably mediated by an increase of aqueous humor formation
      rather than by an inhibition of the outflow of aqueous humor.

PMID- 1362452
TI  - In vivo evidence for a concordant response of terminal and dendritic dopamine
      release during intranigral infusion of drugs.
AB  - In the present study we have administered prototypical drugs of 5 different
      receptors (D-2, GABA-A, GABA-B, NMDA, kainate) to the substantia nigra by
      infusion via a microdialysis probe, whereas the release of dopamine and 3,4
      dihydroxyphenylacetic acid (DOPAC) were recorded both in the substantia nigra and
      (by a second microdialysis probe) in the ipsilateral striatum. Infusion of the
      specific D-2 receptor agonist 2-(N-propyl-N-2-thienylethylamino)-5
      hydroxytetralin ((--)-N0437) into the nigra induced a decrease in the release of
      dopamine in the nigra (after 1 mumol/l) as well as in the ipsilateral striatum
      (after 10 mumol/l). During these infusions extracellular DOPAC decreased in the
      nigra and increased in the striatum. Infusion of the D-2 specific receptor
      antagonist (--)-sulpiride into the nigra induced an increase in the release of
      dopamine in the nigra (after 1 mumol/l) as well as in the ipsilateral striatum
      (10 mumol/l). During these infusions a slight increase of extracellular DOPAC was
      noticed in the nigra. Infusion of the GABA-A receptor antagonist bicuculline into
      the nigra (50 mumol/l) induced an increase in the release of dopamine and DOPAC
      both in the nigra and ipsilateral striatum. Infusion of the GABA-B receptor
      agonist d,I-baclofen into the nigra (10 mumol/l) induced a decrease of in the
      release of dopamine in the nigra as well as in the ipsilateral striatum, whereas
      extracellular DOPAC decreased in the nigra and increased in the
      striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362454
TI  - Characterization of the antagonism with metoprolol, ICI 147,798, pindolol,
      mepindolol and bopindolol on the responses of the rat left atria to isoprenaline.
AB  - The aim of the study was to determine whether the antagonism with pindolol,
      mepindolol and bopindolol at the beta 1-adrenoceptor of the rat left atria, a
      tissue with plenty of spare beta 1-adrenoceptors for isoprenaline maximum
      responses, was readily reversible or not. The effects of these drugs were
      compared to those of metoprolol, a readily reversible, and of ICI 147,798, an
      irreversible beta-adrenoceptor antagonist. Metoprolol at 10(-7) and 10(-6) M, ICI
      147,798, pindolol, bopindolol (all at 10(-8) and 10(-7) M) and mepindolol at 10(
      9) and 10(-8) M inhibited the cardiac stimulation responses to a small extent,
      which is indicative of membrane stabilizing activity, and also caused
      surmountable antagonism of isoprenaline responses. The inhibitory effects on the
      isoprenaline responses of metoprolol and pindolol were readily reversible, that
      of mepindolol was slowly reversible and those of ICI 147,798 and bopindolol were
      not reversed in 3 h. The inhibitory effects on isoprenaline responses of
      metoprolol at 10(-6) M, pindolol and bopindolol at 10(-7) M and mepindolol at 10(
      8) M were at equilibrium, which is indicative of reversible, whereas the
      inhibitory effects of ICI 147,798 were increased, which is indicative of
      irreversible antagonism, when the beta-blocker treatment time was increased from
      1 to 2 h. We conclude that the antagonism with pindolol at the beta 1
      adrenoceptors of the rat left atria is readily reversible, that of mepindolol is
      slowly reversible and that of bopindolol is very slowly reversible.

PMID- 1362455
TI  - Adenosine but not an adenine nucleotide mediates tonic purinergic inhibition, as
      well as inhibition by glutamate, of noradrenaline release in rabbit brain cortex
      slices.
AB  - A possible contribution of adenine nucleotides to the endogenous purinergic, A1
      receptor-mediated inhibition of noradrenaline release was studied in rabbit
      occipito-parietal cortex slices. The slices were preincubated with [3H]
      noradrenaline and then superfused and stimulated electrically, in most
      experiments by trains of 6 pulses/100 Hz. A few experiments were carried out in
      rat occipito-parietal cortex slices. The A1-purinoceptor antagonist 8-cyclopentyl
      1,3-dipropylxanthine (DPCPX; 1-100 nmol/l) as well as the enzyme adenosine
      deaminase (0.1-10 U/ml) increased the electrically evoked overflow of tritiated
      compounds. The maximal increase was by about 85% for both DPCPX and adenosine
      deaminase. The increases obtained with maximally effective concentrations of
      DPCPX and adenosine deaminase were not additive. The alpha 1-adrenoceptor
      selective agonist methoxamine (10 but not 1 mumol/l) reduced the evoked overflow.
      Its effect was antagonized by yohimbine 1 mumol/l but then not attenuated further
      by DPCPX 100 nmol/l. L-Glutamate (300 mumol/l-2.3 mmol/l) also reduced the evoked
      overflow of tritium. Its effect was not changed by yohimbine 1 mumol/l but
      greatly, and to the same extent, attenuated by DPCPX 100 nmol/l and adenosine
      deaminase 3 U/ml. Neither the N-methyl-D-aspartate (NMDA) receptor antagonist
      dizocilpine nor omission of Mg++ changed the inhibition by glutamate. Glutamate
      did not alter the basal efflux of tritium from rabbit cortex slices under any
      experimental condition. In contrast, glutamate (100 mumol/l and 1 mmol/l) caused
      an immediate, marked and transient acceleration of tritium outflow from rat
      occipitoparietal cortex slices (medium without Mg++).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1362456
TI  - [Measurement of PCNA labeling index in astrocytic tumors].
AB  - PCNA (proliferating cell nuclear antigen) is said to be present specifically in
      the nucleus of proliferating cells. The PCNA labeling index (PCNA LI) of
      astrocytic tumors was measured and compared with histological types or prognosis.
      The specimens from 44 patients were fixed in a 10% formalin solution, and
      embedded in paraffin. The 3 microns-sections were stained immunohistochemically
      with anti-PCNA monoclonal antibody (PCIO, Novocastra) using an ABC method. The
      percentage of PCNA-positive-cells was determined by counting 2000 cells, and
      identified as PCNA LI. All of the PCNA-positive-cells showed diffuse
      nucleoplasmic staining. The averages of PCNA LIs in each pathological type were
      calculated and evaluated statistically. Although differences in averages of PCNA
      LIs among pilocytic, gemistocytic, fibrillary astrocytoma were not significant,
      there was a significant difference between anaplastic astrocytoma and
      glioblastoma. The relationship between PCNA LIs and the prognoses for 43 patients
      was studied. Forty-three patients were classified into 3 groups (over 22%, 7 to
      less than 22%, and less than 7%) according to PCNA LIs. The survival data in the
      3 groups were analyzed, and differed significantly in the survival rates.
      Furthermore, twenty-three patients of anaplastic astrocytoma and glioblastoma
      were classified into two groups (over 22% and less than 22%). Likewise, the two
      groups differed significantly. In summary, pathological type and prognosis were
      closely related to PCNA LI in astrocytic tumors. Therefore, we thought
      measurement of PCNA LI would make it more possible to analyze clinically the
      proliferating activity of astrocytic tumors, and to care for patients more
      effectively.

PMID- 1362458
TI  - The depressive effect of intrathecal clonidine on the spinal flexor reflex is
      enhanced after sciatic nerve section in rats.
AB  - The effect of intrathecal (i.t.) alpha 2-adrenoceptor agonist, clonidine, on the
      spinal nociceptive flexor reflex was studied in decerebrate, spinalized,
      unanesthetized rats with intact sciatic nerves or in rats in which the sciatic
      nerve had been ipsilaterally sectioned. In rats with intact nerves i.t. clonidine
      caused a dose-dependent biphasic effect on flexor reflex excitability. At low
      dose (10 ng) the effect of clonidine was purely facilitatory, whereas with 50-100
      ng clonidine the initial facilitation was often followed by reflex depression.
      Long-lasting, strong reflex depression was observed after i.t. injection of high
      doses of clonidine (1 and 10 micrograms). Four to 18 days after sciatic nerve
      section, the depressive effect of clonidine on the flexor reflex was dramatically
      enhanced. Depression was frequently observed already with doses of 5 and 10 ng,
      and maximal depression was reached at 100 ng and 1 micrograms in axotomized rats.
      The facilitatory effect of low doses of clonidine on the reflex was also
      observed, although somewhat less frequently than in normals. The depressive
      effect of clonidine on the flexor reflex was reversed by the selective alpha 2
      receptor antagonist, atipamezole (20 micrograms, i.t.), in rats with both intact
      and sectioned sciatic nerves. The present results revealed an increased
      sensitivity and effectiveness of the depression of spinal reflex mechanisms by
      i.t. clonidine after sciatic nerve section, which is opposite to the decreased
      sensitivity to i.t. morphine after axotomy that we observed previously.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1362459
TI  - Leukocyte integrin activation.
AB  - Certain stages of the immune response require interaction of leukocytes with each
      other and with non-hematopoietic cells. One of the systems implicated in these
      interactions involves an integrin, LFA-1 (Lymphocyte Function Antigen-1),
      expressed by all leukocytes at their cell surface, and a molecule belonging to
      the immunoglobulin superfamily, ICAM-1 (Intercellular Adhesion Molecule-1). The
      avidity of LFA-1 for ICAM-1 is transient. It is modulated both by regulation of
      ICAM-1 expression and by activation of LFA-1 molecules constitutively expressed
      on leukocyte membranes. This activation, which induces a conformational change in
      the molecule, depends on the presence of divalent cations, notably Mg++. This has
      been demonstrated by using a specific monoclonal antibody, MAb 24. In addition to
      being a ligand for LFA-1, ICAM-1 is sometimes used as a cell receptor by
      pathogens such as Plasmodium falciparum, the causative organism of malaria. Very
      careful study of the binding site of this pathogen using specific antibodies,
      mutagenesis studies and the construction of a three-dimensional model of the
      molecule suggests some interesting therapeutic possibilities for the treatment of
      malaria.

PMID- 1362457
TI  - Demonstration of dynorphin A 1-8 immunoreactive axons contacting spinal cord
      projection neurons in a rat model of peripheral inflammation and hyperalgesia.
AB  - Using a double-labeling technique, we evaluated the input of afferents
      immunoreactive for dynorphin peptide onto a population of lumbar spinal neurons
      contributing to the spinoparabrachial tract in rats with 1 inflamed hind paw. We
      found that the frequency and distribution with which dynorphin immunoreactive
      varicosities were in apposition to projection neurons varied according to neuron
      location. In particular, neurons in the superficial dorsal horn and neck of the
      dorsal horn receive a high degree of dynorphin input. We also determine that
      unilateral peripheral inflammation is associated with both an increase in the
      number of projection neurons receiving detectable DYN input and in the frequency
      of this input onto a given neuron, with the largest increase seen in the
      superficial dorsal horn. Since almost all superficial dorsal horn neurons
      contributing to the spinoparabrachial tract respond either exclusively or
      maximally to noxious stimulation, our data supports dynorphin's involvement in
      nociception.

PMID- 1362460
TI  - Benextramine, a putative neuropeptide Y receptor antagonist, attenuates the
      termination of receptivity.
AB  - Sexual behavior in female rats is dependent on gonadal steroids. In
      ovariectomized rats, progesterone treatment typically exerts a biphasic effect on
      copulatory behavior induced by prior treatment with estradiol. Thus, there is an
      initial augmentation of the facilitative effect of estradiol occurring 4-10 h
      after progesterone. This is followed by a profound inhibitory effect, essentially
      terminating receptivity. We hypothesized that the receptivity terminating effect
      of progesterone could be due to increased synthesis and release of neuropeptide Y
      in relevant brain regions. Rats were tested for female sexual behavior 4 h after
      progesterone (52 h postestradiol). Immediately following this test, benextramine
      was administered (0, 3, or 15 mg/kg, IP). Subsequently, behavioral tests were
      administered 24, 48, 72, and 96 h postbenextramine. Benextramine treatment
      attenuated the inhibitory effects of progesterone on receptivity (lordosis
      quotients and percent of responding animals) without affecting either proceptive
      or rejection behaviors. These data suggest that blockade of NPY (and alpha
      adrenergic) receptors is associated with selective enhancements of specific
      components of sexual behavior in female rats. Specifically, blockade of NPY
      receptors by benextramine is associated with continued receptivity.

PMID- 1362461
TI  - Cryptosporidiosis in HIV-seropositive patients.
AB  - The incidence of cryptosporidiosis in our unit has increased over the last 6
      years, being diagnosed in approximately 5 per cent of all patients with HIV
      infection and in 21 per cent of those with AIDS, but a marked seasonal variation
      occurs. We have studied the course of the infection in 128 patients and
      identified four clinical patterns of disease: transient (28.7 per cent), chronic
      (59.7 per cent), fulminant (7.8 per cent) and asymptomatic (3.9 per cent).
      Transient disease occurred in patients with a wide range of CD4 lymphocyte
      counts, but was more common in less immunosuppressed patients. Fulminant disease,
      defined by the passage of more than 2 l of stool/day from the time of
      presentation, only occurred in patients with a CD4 count less than 50/mm3. This
      group had lost more than 7 kg in weight at presentation and more commonly had
      other intercurrent gastrointestinal infections. They survived for a median of
      only 5 weeks, compared with 20 weeks for those with chronic diarrhoea and 36
      weeks for those with transient infection. The survival was unaffected by any
      treatment other than zidovudine. Cryptosporidiosis in HIV-infected individuals is
      a heterogeneous disease.

PMID- 1362462
TI  - Renovascular hypertension due to Takayasu's arteritis among Indian patients.
AB  - Over a 16-year period, 205 patients with hypertension were shown to have a
      renovascular aetiology. Of these, 125 (61 per cent) had Takayasu's arteritis, 58
      (28.3 per cent) had fibromuscular dysplasia, 16 (7.8 per cent) had
      atherosclerosis, five (2.4 per cent) had polyarteritis nodosa and one (0.5 per
      cent) had renal artery aneurysm. Among patients with Takayasu's arteritis, males
      were affected as commonly as females. The mean age of these patients at the time
      of detection was 26.8 +/- 8.6 years (range 5-52 years). Type I arteritis was seen
      in nine (7.2 per cent), Type II in 40 (32 per cent) and Type III in 76 (60.8 per
      cent) patients. The abdominal aorta was involved in 117 (93.3 per cent) patients.
      Takayasu's arteritis was associated with ulcerative colitis in two patients and
      with renal amyloidosis and focal segmental glomerulosclerosis with a nephrotic
      syndrome in one patient each. Surgical intervention consisting of bypass
      procedures, autotransplantation or nephrectomy was performed in 17 (13.6 per
      cent) and angioplasty in nine (7.2 per cent) patients. Cure and improvement in
      blood pressure was observed in 82.4 per cent and 77.8 per cent respectively.
      Adequate control of blood pressure was achieved with drugs only in 22 (22.2 per
      cent) patients. A definite cause and effect relationship could not be established
      between any infective or immunological disorder and Takayasu's arteritis.
      Takayasu's arteritis is a far more common cause of renovascular hypertension in
      Indian population than fibromuscular dysplasia or atherosclerosis, which are more
      common in the western population.

PMID- 1362464
TI  - Histochemistry of receptors. Proceedings of the 33rd Symposium of the Society for
      Histochemistry. Ghent, Belgium, September 18-21, 1991.

PMID- 1362463
TI  - Robert Feulgen Lecture 1991. Control and role of major signalling cascades of the
      thyrocyte.

PMID- 1362465
TI  - Identification of alpha 2 adrenoceptors in the human nucleus olivarius by
      radioligand binding.

PMID- 1362467
TI  - [Association of Takayasu arteritis, Crohn disease and pregnancy].
AB  - The authors report a case of a pregnant woman with Takayasu's arteritis and
      Crohn's disease. The course of pregnancy was uneventful. It is suggested that
      these two inflammatory diseases may be immunologically related. A brief review of
      the literature confirm that fetal and maternal prognosis are generally excellent.

PMID- 1362466
TI  - [52 year-old man with colonic polyposis, colon adenocarcinoma and hepatic
      tumors].

PMID- 1362468
TI  - [Therapeutic perspectives of sickle cell anemia].
AB  - After a long gestation new therapies are at hand. At the present time about 30
      patients have been cured with the bone marrow transplantation. The potential use
      of cord blood, rich in hematopoietic stem cells, is under development as an
      alternative for bone marrow transplantation. The activation of HbF expression
      upon hydroxyurea (Hydrea) and other agents which is under clinical trials. The
      agent 12C79 which increases the oxygen affinity of sickle cells in vivo and
      prevent HbS polymerization is in clinical development. Membrane acting agents
      which inhibit sickle cell dehydration are another approach to be developed. The
      inhibition of vascular cell adhesion, of inappropriate clotting formation and of
      inadequate response to vaso-occlusive events needs to be developed. Finally the
      gene therapy is a very promising avenue.

PMID- 1362469
TI  - [Rheumatoid arthritis. Changes in lymphocyte subsets under the effect of
      tiopronin].
AB  - Lymphocytes from 12 rheumatoid arthritis patients were phenotyped before and
      after a 2-month treatment with tiopronin. Originally reduced, CD4 CD45RA-T
      lymphocytes were shown to augment significantly. Abnormal activation (evaluated
      on HLA-DR and CD25 expression) of each cell population and sub-population was
      partially amended.

PMID- 1362471
TI  - Serotonin-Mediated Emesis: The Role of Ondansetron. Proceedings of a symposium.
      Fort Lauderdale, Florida, April 24-26, 1992.

PMID- 1362470
TI  - Recent Advances in Ifosfamide Therapy. Proceedings of a symposium. Houston,
      Texas, May 17, 1991.

PMID- 1362472
TI  - [Non-palpable testes--diagnosis and therapy].
AB  - The authors subject to a retrospective analysis a group of 522 boys operated on
      account of retention of the testes during 1982-1991, whereby they focused
      attention on cases where the testis was not palpable before operation. In 57
      (10.9%) of the boys with a non-palpable testis in three instances the finding was
      bilateral and in 54 cases unilateral. Surgical revision of 60 testicles revealed
      anorchia in 14 instances (23.3%), inguinal retention in 25 (41.7%) and abdominal
      retention in 21 (35.0%). Orchiopexy was performed in 31 boys and orchiectomy in
      15. The therapeutic results are unfavourable in particular in the group of boys
      with intraabdominal retention. The mentioned state of affairs can be improved
      only by initiating treatment at the age of 1 year, making use of microsurgery and
      laparoscopy in the diagnostic and therapeutic process.

PMID- 1362473
TI  - Sea anemone Radianthus macrodactylus--a new source of palytoxin.
AB  - A very potent non-protein toxin was isolated from the sea anemone Radianthus
      macrodactylus with the use of chromatography on polytetrafluoroethylene, CM
      Sephadex C-25 and by cation and anion exchange HPLC. The toxin was identified as
      palytoxin by u.v.-, i.r.- and 500 MHz 1H NMR spectroscopy. Its LD50 was 0.74 +/-
      0.29 micrograms/kg by i.v. injection into mice. So far, palytoxin has been
      associated with zoanthids only. The toxin caused the loss of haemoglobin from
      erythrocytes but only in about 2 hr after the beginning of incubation, which is
      characteristic for palytoxin from zoanthids. Sea anemone palytoxin was divided
      into major and minor components by HPLC. The latter proved to be a product of
      degradation of palytoxin.

PMID- 1362475
TI  - Functional Regulation of Bone Cell Biology by Mechanical Factors. Proceedings of
      the European Calcified Tissue Workshop. Vienna, Austria, March, 14, 1991.

PMID- 1362474
TI  - Treatment with neuroleptics: the patient's perspective.
AB  - Sixty-one acute schizophrenic patients were questioned on the effects ascribed
      subjectively by them to their neuroleptic medication and on their rating of
      neuroleptic therapy. Although negative effects ascribed to the medication
      outnumbered positive effects by 3 to 1, the global rating was predominantly
      positive. Patients approving of neuroleptic therapy reported favourable changes
      under medication significantly more often than patients with a rejecting
      attitude. There was, however, no significant difference between the two groups in
      the frequency with which negatively experienced effects of medication were
      described.

PMID- 1362477
TI  - Multidrug resistant gene 1 product in human T cell subsets: role of protein
      kinase C isoforms and regulation by cyclosporin A.

PMID- 1362476
TI  - On the regulation of beta 2 integrins.
AB  - The complex functions played by beta 2 integrins in mediating a large variety of
      adhesive interactions of leukocytes are highly regulated. This regulation results
      in transient adaptations/associations, permitting physical and functional
      recycling of these receptors during chemotaxis, phagocytosis and target-cell
      killing. The structural definition of these adaptations will lead not only to a
      better understanding of how these receptors are regulated in leukocytes but also
      shed valuable light on how these integrins integrate diverse extracellular
      signals into spatially and temporaly coordinated cellular responses.

PMID- 1362479
TI  - [Immunogenetic and molecular genetic studies on ocular diseases].
AB  - The immunogenetic mechanisms of various ocular diseases were investigated
      utilizing recently developed molecular biological and molecular genetic
      techniques. It was revealed that HLA-B 51 was closely associated with Behcet's
      disease. Investigation of genetic polymorphism of TNF-beta (tumor necrosis factor
      beta) showed that 95% of Behcet's disease patients had the 10.5 kbp Nco I
      fragment. It was therefore concluded that the gene of susceptibility to Behcet's
      disease is located between HLA-B and TNF-beta loci on the short arm of chromosome
      6. Similar studies of HLA-DNA typing in Harada's disease frequently seen in Japan
      showed that frequencies of HLA-DRB1 * 0405, HLA-DQA1 * 0301 and HLA-DQB1 * 0401
      were significantly increased in patients compared with normal controls. These
      data suggested that those who have serine at position 57 of HLA-DR, glutamic acid
      at position 70 and aspertic acid at position 71 of HLA-DQ respond to certain
      unknown agents significantly more than those without them, thus leading to the
      development of Harada's disease. The same HLA association was observed between
      Harada's disease and sympathetic ophthalmia, and the immunogenetic mechanism was
      thought to be similar in both diseases. Recent immunogenetic and molecular
      genetic investigations on various ocular diseases have shed new light not only on
      the genetic individual susceptibility and biased racial differences, but also on
      the diagnosis of the ocular diseases, reclassification of disease entities
      according to HLA associations, and judgement of disease prognosis. Further
      progress of molecular medicine may make it possible to treat various intractable
      ocular diseases by gene therapy in the near future.

PMID- 1362478
TI  - Lymphocyte development in mice deficient for MHC class I expression.

PMID- 1362480
TI  - [Long-term outcome of cryptorchism after orchiopexy].
AB  - The long-term outcome of cryptorchism (undescended testis) was studied in 43
      patients who underwent orchidopexy at pre-puberty ages and who were over 15 years
      of age at the time of this study. The follow-up period after operation was 11
      approximately 23 years. Cryptorchism was unilateral in 39 patients and bilateral
      in 4 patients. The sperm concentration and motility were examined, using a cut
      off level of 20 x 10(6)/ml for sperm concentration and 50% for sperm motility. In
      the unilateral cryptorchism group, 16 patients (61.5%) had normal semen quality,
      8 patients (30.8%) oligozoospermia, 1 (3.8%) asthenozoospermia and 1 (3.8%)
      azoospermia. In the bilateral cryptorchism group, 3 patients (75.0%) were normal
      and 1 (25.0%) had azoospermia. Eight patients with unilateral cryptorchism were
      married and 7 of them (87.5%) had children. The sperm concentration had no
      inverse correlation with the age at operation. In patients with unilateral
      cryptorchism, the testicular volume on the healthy side was significantly higher
      than that on the affected side. The sperm concentration tended to correlate with
      the testicular volume on the healthy side rather than that on the affected side.
      These findings suggest that the sperm profiles in patients with unilateral
      cryptorchism are chiefly associated with the testicular function on the healthy
      side.

PMID- 1362481
TI  - Twelve months, treatment with inhaled salmeterol in asthmatic patients. Effects
      on beta 2-receptor function and inflammatory cells.
AB  - Salmeterol is a new beta 2-receptor agonist with a prolonged duration of action
      after inhalation, exceeding 12 h in most patients. We have performed a 12-month
      open follow-up study on 11 patients with reversible asthma. All patients were
      given salmeterol inhalations (50 micrograms twice daily). Additional asthma
      treatment included inhaled corticosteroids in all patients, and oral slow-release
      theophylline or beta 2-receptor agonists in a minority of patients (3 and 1,
      respectively). Before salmeterol treatment was initiated and after 3, 6, 9 and 12
      months of salmeterol treatment, a cumulative dose-response curve to inhaled
      salbutamol (100, 300 and 900 micrograms) was performed, and FEV1 measured. We
      also evaluated the effect of each salbutamol dose on finger tremor, systemic
      blood pressure and heart rate. Blood tests, including white blood count and
      electrolytes, were taken at each visit. After salmeterol treatment was initiated,
      morning FEV1, measured before the morning asthma medication, was significantly
      improved (p < 0.05). The responsiveness to inhaled salbutamol was not decreased
      during salmeterol treatment, except in one patient with asthma worsening over the
      study year. Baseline finger tremor measured before salbutamol dose-response
      curves, was significantly lower at the 12-month visit than before treatment was
      initiated (p < 0.05). Effects of salbutamol on systemic blood pressure, heart
      rate or finger tremor was not significantly changed during salmeterol treatment.
      We found a successive and significant decrease in blood eosinophils (p < 0.05)
      during the 12 months of salmeterol treatment, when the patient with asthma
      worsening was excluded in the analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362482
TI  - [A comparative evaluation of the efficacy of certain types of premedication in
      children].
AB  - Mathematical analysis of the heart rhythm and expressive methods of emotional
      stress determination have been used in 90 children prepared for surgical
      intervention with the help of three types of premedication. It has been shown
      that premedication with diazepam and droperidol (according to scheme) was
      effective for the elimination of preoperative psychoemotional stress in children.

PMID- 1362483
TI  - [Endogenous humoral regulators directly before an operation].
AB  - It has been shown that modern premedication techniques do not prevent the
      activation of the sympathoadrenal system and the enhanced synthesis of cyclic
      nucleotides and prostaglandin-like compounds in response to preoperative stress.
      In a great number of patients there are no hemodynamic shifts in the nearest
      preoperative period, as an increased production of prostaglandins E and cyclic
      nucleotides (cAMP), that is of compensatory value, is observed. When normal
      relations between endogenous vasoactive substances with constricting and dilating
      effects are damaged, a hyperdynamic reaction ensures.

PMID- 1362485
TI  - Physiopathological Processes of Aging. Towards a Multicausal Interpretation.
      Proceedings of the 4th International Congress of the International Association of
      Biomedical Gerontology. Ancona, Italy, June 26-29, 1991.

PMID- 1362486
TI  - 13th meeting of the European Intra-Renal Surgery Society. Como--Villa d'Este,
      September 22-23, 1990.

PMID- 1362484
TI  - [Opioids and their antagonists in the regulation of vasopressin secretion].

PMID- 1362487
TI  - Coexisting HLA-B27 positive spondyloarthritis and polyarteritis nodosa.
AB  - A 38 year old woman presented with widespread polyarteritis nodosa a few years
      after the onset of HLA-B27 positive spondyloarthritis. The concomitant
      coexistence of these two disorders suggests a possible association in this
      genetically susceptible subject.

PMID- 1362488
TI  - Polyarteritis nodosa and acute interstitial pneumonia.

PMID- 1362489
TI  - Symposium: Role of Granulocytes in Immunology. Spala, Poland, June 20-22, 1991.

PMID- 1362490
TI  - Neutrophil--mediated cytotoxicity against tumour cells: state of art.
AB  - When activated by a variety of stimuli, human neutrophils become capable of
      lysing tumour cells. The main physiologic cytotoxic trigger in neutrophils is
      represented by the surface receptor for the Fc domain of IgG (FcR). This receptor
      confers specificity to the target recognition by neutrophils and cooperates with
      adhesion glycoproteins (CD11-CD18) in the neutrophil-target conjugate formation.
      Although the FcR-dependent pathways of signal transduction remain to be
      clarified, the neutrophil responses involve both the production of oxidants and
      the release of granule constituents. These molecules are responsible for the
      target lysis, whose extent also depends on the target structural and metabolic
      characteristics. The use of monoclonal antibodies specific for tumour cell
      antigens, coupled with appropriate cytokines, may provide rational basis for
      designing trials to employ the neutrophil cytotoxic potential as adjuvant therapy
      in cancer patients.

PMID- 1362491
TI  - Diminished integrin expression on granulocytes from renal allograft recipients.
AB  - Integrin (beta 2 subunit of the LEU-CAM family, CD18) expression on peripheral
      blood and urinary granulocytes was studied in renal allograft recipients.
      Circulating granulocyte CD18 expression was normal except for patients with CMV
      infection. In contrast, the majority of patients with urinary tract infection had
      low numbers of CD18+ cells collected from urine, and the same abnormality could
      also be observed in approx. 50% of non-infected recipients. These disturbances
      were associated with transplantation, as no such deficits were seen in the
      infected non-transplant patients or patients with glomerular diseases on
      immunosuppression. Short culture of granulocytes with immunosuppressants did not
      diminish integrin expression. Deficient granulocyte integrin expression,
      especially in urinary tract, may be associated with increased susceptibility to
      infection in renal transplant recipients, although immunosuppression alone could
      not be incriminated as a sole factor responsible for this deficit.

PMID- 1362492
TI  - Plasmid analysis and epidemiology of Salmonella enteritidis infection in three
      commercial layer flocks.
AB  - Ninety-six S. enteritidis isolates obtained from three commercial layer flocks in
      1988-90 were examined following DNA extraction, restriction enzyme digestion, and
      gel electrophoresis for plasmid size profiles and restriction fragment length
      polymorphisms (RFLPs). The S. enteritidis isolates from the three flocks had
      three, eight, and two different plasmid profiles, respectively. Only four
      isolates from one flock lacked plasmids. A 36-megadalton (mDa) (54-kilobase)
      plasmid was present in 73% of the isolates, either alone or in combination with
      other plasmids. Isolates with only the 36-mDa plasmid had identical RFLPs. The
      diversity of plasmid profiles was greater than that of phage-types among isolates
      from the three flocks: 12 unique plasmid profiles vs. four phage-types. Mixed
      infections with S. enteritidis strains having distinct plasmid profiles occurred
      in all three flocks. Reinfection of these flocks in 1990 with one or more of the
      strains obtained earlier was evident, because some of the original isolates and
      the 1990 isolates had matching plasmid profiles and were of the same phage-types.
      Isolates from both environmental and tissue samples, examined from one flock,
      were found to share the same plasmid profile and phage-type.

PMID- 1362494
TI  - 6th International Symposium of the Working Party for Culture Media. Proceedings.
      Heidelberg, Germany, 30 March-3 April 1992.

PMID- 1362493
TI  - Sequence analysis of the int-2/fgf-3 gene in aggressive human breast carcinomas.
AB  - A number of primary human breast carcinomas exhibit amplification of the
      chromosome 11 region containing the int-2/fgf-3 proto-oncogene, and progression
      of breast cancer has been correlated with int-2 amplification or with certain
      restriction fragment length polymorphisms (RFLPs) of the int-2 gene. Using the
      polymerase chain reaction (PCR), we obtained the int-2 coding sequences from six
      primary tumors, four of which exhibited amplification of the int-2 gene and one
      of which exhibited amplification of the neu gene. The majority of these tumors
      (five of six) were aggressive, as judged by their early recurrence, metastasis,
      or both. Nucleotide sequencing of PCR products revealed that previously described
      BamHI and PstI RFLPs of the int-2 gene, as well as a new polymorphism at position
      9154, were located within the intron between the second and third exons. A
      seventh tumor was used to localize one of the PstI RFLPs 5 bp from the splice
      acceptor site of the third exon. However, none of the tumor DNAs analyzed showed
      differences in the int-2 protein coding regions when compared with normal
      placenta DNA. These results imply that aggressive human breast cancers encode an
      unaltered form of the int-2 protein.

PMID- 1362495
TI  - A distinct large granular lymphocyte (LGL)/NK-associated (NKa) abnormality
      characterized by membrane CD4 and CD8 coexpression.  The Yorkshire Leukaemia
      Group.
AB  - In a study of 870 individual patients with either lymphocytosis (excluding known
      lymphoproliferative disease), increased proportions of blood lymphocytes with
      granular morphology (LGL), or neutropenia, 14 cases were found with abnormally
      increased CD3+CD4+CD8+ components. Eleven of these were further investigated and
      10 shown in follow-up studies to be persistent in nature. Morphological
      assessments revealed increased LGL in 9/11 cases, and in seven of these > 50%
      lymphocytes had discernable cytoplasmic granulation. Immunophenotypic studies
      indicated that CD8 expression by CD4+ lymphocytes in these patients was of low
      density (CD8dim+), and that both the CD4+CD8- and CD4+CD8dim+ fractions in each
      patient was characterized by a CD11b+CD16-CD56+CD57+ composite NK-associated
      (NKa) phenotype (in contrast to normal CD4+CD8- blood lymphocytes and CD4+CD8+
      thymocytes which were consistently CD11b-CD16-CD56-CD57-). TCR genotypic studies
      revealed rearranged components (beta plus gamma, or beta alone) in 5/11 cases,
      but there were no obvious relationships between TCR configuration (including
      rearranged band densities) and immunophenotypes, absolute lymphocyte or
      neutrophil numbers, the proportions of blood LGL, or the proportions of CD4+
      cells coexpressing CD8. The occurrence of identical NKa phenotypic profiles in
      both germline and rearranged TCR cases does, however, suggest the possibility of
      an evolutionary process from a non-clonal expansion to a clonal state. Serum
      studies, including soluble CD4, CD8 and IL2-R concentrations and autoantibody
      investigations, of representative germline and rearranged TCR cases failed to
      indicate any consistent abnormalities, but there was some suggestion for the
      existence of a chronic reactive process in some of the patients with germline
      TCR. These findings suggest that expanded LGL/NKa+ components with phenotypic
      evidence of CD4/CD8 coexpression should be regarded as a distinct diagnostic
      category and that persistent CD4+CD8+ abnormalities with germline TCR should be
      monitored for possible clonal transition.

PMID- 1362497
TI  - Ranitidine, cimetidine, famotidine have no effect on post-prandial absorption of
      ethanol 0.8 g/kg taken after an evening meal.
AB  - Forty-seven healthy male subjects were studied twice using a randomized, placebo
      controlled design. Each subject took an 8-day course of two of the following four
      regimens; 300 mg ranitidine, 800 mg cimetidine, 40 mg famotidine or placebo
      (identical either to 300 mg ranitidine or 800 mg cimetidine). The systemic
      bioavailability of ethanol (integrated 6-h plasma ethanol concentration, peak
      plasma ethanol concentration, and the time to peak plasma ethanol concentration)
      was measured after the oral ingestion of 0.8 g of ethanol per kg body weight,
      given one hour after an evening meal on Day 8 of each regimen. There was no
      significant difference of integrated 6-h plasma ethanol concentration, peak
      ethanol concentration, or time to reach peak ethanol concentration after dosing
      with either ranitidine, cimetidine or famotidine or placebo.

PMID- 1362496
TI  - Psychomotor disturbances in psychiatric patients as a possible basis for new
      attempts at differential diagnosis and therapy. V. Evaluation of psychomotor
      training programs in depressed patients.
AB  - Parts I-III of this series used psychometric assessment of motor performance in
      psychiatric patients and indicated a "psychotic-motor syndrome" (PMS) in
      schizophrenic and affective psychoses, which was not found in "neurotic"/reactive
      or healthy persons. Part IV yielded signs of concomitant brain dysfunction in
      these patients, demonstrated by EEG mapping as well as other (SPECT/PET)
      neuroimaging methods. Apart from this "basic science" interest into the
      pathophysiology of endogenous psychoses we engaged in the development of motor
      training programs using the PMS as "target" syndrome. We hypothesized, that motor
      training would not only improve disturbed motor behaviour, but ameliorate other
      symptoms of psychopathology also. These assumptions were supported in the first
      two independent studies involving n = 45 and n = 31 ICD-9 mono- and/or bipolar
      endogenous depressed patients, respectively (the studies on schizophrenic
      patients being reported finally as part VI of this series, along with the final
      version of our modified motor test battery). Examples of the motor training
      programs are provided in this paper, although the final version of the complete
      programs will be published separately for space reasons and for better
      availability for routine clinical use.

PMID- 1362498
TI  - Is stress ulcer bleeding still an obnoxious killer in present day ICU?

PMID- 1362500
TI  - Clonal deletion of V beta 17 T cells in mice from natural populations.
AB  - In a panel of wild mice trapped in different geographical regions, the
      concomitant expression of V beta 17 T cell receptors and I-E histocompatibility
      molecules is frequent. By Southern blot analysis, eight forms of V beta 17 genes
      have been distinguished that encode five kinds of V beta 17 domains. Populations
      of Asia display the highest level of polymorphism and include all the V beta 17
      forms and domains. The V beta 17 T cells of wild origin are deleted in mice
      expressing Mls-3 and related superantigens. Wild mice use V beta 17 domains
      different than the one of laboratory strains. Together with endogenous
      superantigens polymorphism, this accounts for the observed low frequency of
      clonal deletion cases in natural populations.

PMID- 1362499
TI  - A meta-analysis comparing the efficacy of omeprazole with H2-receptor antagonists
      for acute treatment of duodenal ulcer in Asian patients.
AB  - A meta-analysis was performed on pooled data from five large double-blind studies
      (a total of 1057 patients), which were conducted in Asia to compare the effects
      of omeprazole with H2-receptor antagonists (H2-RA) in duodenal ulcer. As each
      study followed the same protocol and data evaluation procedures, a detailed
      analysis of ulcer healing, symptom relief and influence of prognostic factors
      across the data was possible. Patients received omeprazole 20 mg om or standard
      doses of H2-RA for a minimum of 2 and a maximum of 4 weeks, depending on healing
      (as verified by endoscopy). All efficacy analyses were based on per protocol
      data. The mean healing rates at 2 weeks were 72% for omeprazole and 42% for H2-RA
      (difference 30%; 95% CI: 24-36%; P < 0.0001) and at 4 weeks were 96% for
      omeprazole and 83% for H2-RA (difference 13%; 95% CI: 10-17%; P < 0.0001). In
      addition to treatment, ulcer size had a significant influence on healing, with
      large ulcers (diameter > 10 mm) taking longer to heal than small ulcers. There
      was no significant influence of smoking and alcohol drinking on ulcer healing.
      Patients on omeprazole experienced significantly less epigastric pain after 2
      weeks than those on H2-RA, 79% of them being completely symptom-free on
      omeprazole compared with 65% on H2-RA. The incidence of adverse events was
      approximately 5% on each treatment and profiles were similar for each drug. It is
      concluded that omeprazole, even in the presence of adverse prognostic influences,
      results in significantly better healing of duodenal ulcer and relief from
      symptoms than H2-RA.

PMID- 1362501
TI  - Diagnostic procedures and endoscopic measures for bile duct stones.

PMID- 1362502
TI  - Non-surgical management of bile duct stones refractory to routine endoscopic
      measures.
AB  - Endoscopic sphincterotomy and percutaneous approaches to the biliary tract have
      revolutionized the treatment of bile duct stones. Both the endoscopic and
      transhepatic approaches are less invasive than open surgery. This is an advantage
      for the mostly elderly and frail patients with common bile duct stones. Other
      patients with intrahepatic stones, e.g. young patients with oriental lithiasis,
      may also profit from the non-surgical approach. In this latter group it is often
      difficult for the surgeon to obtain access to the stone-bearing bile ducts. Due
      to the anatomical situation, size or impaction of stones the non-surgical
      approach, including mechanical disintegration, may primarily fail. Several
      techniques such as intracorporeal lithotripsy using electrohydraulic probes or
      laser light, extracorporeal shockwave lithotripsy or direct contact dissolution
      are now available and often allow complete clearance of the bile ducts. If a
      kidney lithotripter with radiographic devices is available, it should be used
      after an attempt at mechanical lithotripsy has failed (Figure 1). According to
      the literature, experience with this method is greater than with any other 'third
      step approach'. The procedure is simple, relatively safe and successful in
      approximately 80% of patients. However, in at least one third of patients,
      several sessions have to be performed and further endoscopy is frequently
      required for extraction of fragments. Intracorporeal techniques may become the
      procedure of choice in the future, at least in patients with common bile duct
      stones. At the moment, however, the different devices are still not fully
      developed and too susceptible to damage. A further major drawback, especially
      with high-energy electrohydraulic intracorporeal lithotripsy, is the danger of
      bile duct injury or even perforation, so that most procedures must be performed
      under optical control. The use of contact dissolution cannot generally be
      recommended. Treatment with mono-octanoin or modified mono-octanoin solvents
      takes too long, is often not successful and has a high rate of side-effects. MTBE
      may shorten the procedure considerably, but is suitable only for cholesterol
      stones, and the danger of spill-over into the intestine with absorption and
      systemic side-effects has to be weighed against the probability of success.

PMID- 1362503
TI  - N-benzyladriamycin-14-valerate and drug resistance: correlation of anthracycline
      structural modification with intracellular accumulation and distribution in
      multidrug resistant cells.
AB  - N-Benzyladriamycin-14-valerate (AD 198) is a highly hydrophobic analogue of
      Adriamycin (ADR) which can circumvent multidrug resistance (MDR) in various cell
      lines. Unlike ADR, AD 198 avoids extrusion by P-glycoprotein (P-gp) in AD 198
      resistant murine macrophage-like J774.2 cells and localizes in the cytoplasm. To
      determine the structural modification(s) responsible for these different
      characteristics, intracellular accumulation and distribution of ADR, AD 198, and
      the two half-substituted AD 198 congeners. N-benzyladriamycin (AD 288) and
      adriamycin-14-valerate (AD 48), were analyzed in AD 198-sensitive (J774.2) and 
      resistant (A300) cells. A300 cells exhibited cross-resistance to and reduced
      accumulation of ADR, AD 48, and AD 288. ADR and AD 288 rapidly localized in the
      nuclei of parental and A300 cells, while AD 48 and AD 198 localized in the
      cytoplasm. AD 48 redistributed into nuclei and cytoplasm of both cell lines, but
      AD 198 maintained a punctate cytoplasmic distribution in A300 cells. These
      results suggest that both the N-benzyl and C14-valerate substitutions of AD 198
      are required for P-gp circumvention and stable cytoplasmic localization in A300
      cells, probably as a result of differing intracellular drug trafficking.

PMID- 1362504
TI  - Benzquinamide inhibits P-glycoprotein mediated drug efflux and potentiates
      anticancer agent cytotoxicity in multidrug resistant cells.
AB  - We have previously shown that efflux of cytotoxic drugs from multidrug resistant
      (MDR) cell lines can be quantitated at the single cell level using a sensitive
      fluorescence microscopy technique. Based on the structure of compounds which
      inhibited the efflux of Rhodamine-123 (Rho-123) using this methodology, we
      hypothesized that the antiemetic, antihistaminic agent benzquinamide (BZQ) would
      interfere with P-glycoprotein (P-gp) mediated drug transport and potentiate the
      effects of anticancer agents in MDR cell lines. We show that BZQ interferes with
      P-gp mediated drug efflux and increases drug accumulation in MDR cells using Rho
      123 as a fluorescent probe. BZQ increases the cytotoxicity of chemotherapeutic
      agents to both human and hamster MDR cell lines in vitro. A slight increase in
      cytotoxicity to chemotherapeutic agents is also observed in the parental cell
      lines with BZQ. BZQ increases [3H]daunorubicin accumulation and inhibits the
      binding of [125I]iodoaryl azidoprazosin to the P-gp in MDR cells. BZQ is a new
      agent to increase the cytotoxic effects of anticancer agents in MDR cells and may
      ultimately prove useful as an adjunct in cancer chemotherapy.

PMID- 1362506
TI  - [Report of the ASCO and AACR II congress, San Diego, 17-23 May 1992. Plenary
      session and urologic oncology sessions].

PMID- 1362505
TI  - [Go France ... ASCO/AACR congress, San Diego I, 17-23 May 1992].

PMID- 1362508
TI  - [Are metipranolol eyedrops responsible for intraocular side effects?].
AB  - Metipranolol is a beta-blocker that has been used in ophthalmology and in
      systemic therapy for about 10 years. Reports about reversible uveitis under the
      product Glauline (metipranolol-containing eye drops) in England were the reason
      for extensive studies with metipranolol-containing eye drops produced with
      different methods. Analytical studies concerning the influence of irradiation
      sterilization on the drug containers, studies on the toxicity of the ophthalmic
      drug on tissue cultures, and prospective and retrospective clinical studies on
      2,800 glaucoma patients were performed. Irradiation sterilization leads to the
      formation of free radicals on the surface of the containers and, depending on the
      radiation dose, to a decrease in the pH of the drug solution. In prospective
      studies involving 1,516 glaucoma patients, no intraocular side effects due to
      metipranolol-containing eye drops were found. In the retrospective examination
      including 1,306 glaucoma patients, 19 cases of uveitis were found. Thirteen cases
      of recurring iritis were diagnosed, which had already been observed before the
      onset of glaucoma therapy. In 2 cases the iritis led to secondary glaucoma and
      was treated with metipranolol. In 2 cases glaucoma was treated with pilocarpine
      (and dipivefrin) and metipranolol concomitantly. One case of rubeosis iridis was
      incorrectly classified as iritis. One case is possibly related to metipranolol
      despite the assessment to the contrary by the ophthalmologist in question.
      Following the results of these studies, an accumulation of cases of uveitis
      caused by metipranolol can be excluded.

PMID- 1362509
TI  - The significance of aminopeptidases and haematopoietic cell differentiation.
AB  - Aminopeptidases are a group of enzymes found on the cell surface and in the
      cytoplasmic compartments of many peripheral blood cell types and their
      progenitors. Their functional roles include the hydrolysis of several
      biologically active peptides and growth factors and some have proved to be of
      diagnostic and prognostic value in leukaemia. These enzymes may also be found in
      serum as a consequence of non-haematopoietic related diseases and so have been
      used as indicators of liver damage. Haematopoietic cells in the bone marrow go
      through a process of growth and differentiation before being released into the
      peripheral circulation where they fulfill many functional roles. The enzyme
      activities of some aminopeptidases have been shown to modulate the growth of
      these cells. In addition, the activities of these enzymes themselves can be
      regulated by haematopoietic growth factors. However, the mechanisms that regulate
      their expression and activity are not fully understood. In this report the
      current literature has been reviewed for evidence of expression, regulation and
      clinical significance.

PMID- 1362507
TI  - Gene expression, signal transduction and tissue-specific biomineralization during
      mammalian tooth development.
AB  - Tooth development provides a paradigm for intrinsic molecular controls for cell-
      and extracellular matrix (ECM)-mediated biomineralization. The intent of this
      review is to evaluate the sequential timing and positional information
      prerequisite for tissue-specific biomineralization. Recent investigations suggest
      that 1,25-dihydroxyvitamin D3 functions to up-regulate VDR (vitamin D receptor)
      that in turn could induce structural gene products, including calcium-binding
      proteins and several ECM proteins (e.g., enamelins, amelogenins, dentine
      sialoglycoproteins (DSP) and dentine phosphoproteins (DPP)), resulting in dentine
      and enamel formation. Inhibition of regulatory gene products and/or their
      receptors likely results in hypoplastic and/or hypomineralized ECM as a direct
      consequence of down-regulated (1) transcription and/or translation of structural
      and regulatory genes, (2) posttranslational modifications, (3) and/or decreased
      calcium transport to the forming dentine and enamel matrices. Advances in
      serumless in vitro culture methodology; computer-assisted access to nucleic acid
      sequences for probes to define when, where, and how many specific regulatory and
      structural gene products are expressed; antisense oligodeoxynucleotides to
      inhibit specific translation; and microtechniques to analyze biomineralization
      all provide additional avenues to investigate tissue-specific biomineralization.

PMID- 1362510
TI  - Abnormalities of insulin-like growth factor (IGF-I and IGF-II) genes in human
      tumor tissue.
AB  - Recent findings have indicated that Insulin-like growth factors (IGF-I and IGF
      II) may play a role in neoplasia. Expression of their genes, which are highly
      complex structures, is tissue-specific and developmentally regulated. The purpose
      of the present study was to determine whether a relationship exists between
      tumorigenesis and the structure and expression of IGF genes. The structures of
      the IGF-I and IGF-II genes were investigated in 40 tumors by Southern blot
      analysis but no obvious re-arrangements (such as amplification or deletion) were
      observed in any of the tissues investigated. DNA methylation was also studied,
      using the enzyme Avall. The extent of DNA methylation of the IGF genes was highly
      variable in most of the tumors, as was the level of mRNA expression. A
      relationship could be detected between IGF over-expression and gene demethylation
      in tumors associated with hypoglycemia and in certain hepatocarcinomas. Loss of
      heterozygosity has been reported in the 11p15 region of some childhood tumors.
      The present findings provide further evidence of this loss of heterozygosity for
      the IGF-II gene and show an imbalance in the leukocyte alleles in several
      childhood tumors. Likewise, an imbalance in the alleles was noted in several
      adult tumors, including hepatocarcinomas and breast cancers. This suggests that
      in certain adult tumors alterations of the IGF-II gene may be associated with
      tumorigenesis, but in other tumors another mechanism may be involved.

PMID- 1362511
TI  - [Species differences in the action of concurrent NMDA receptor antagonists in
      mouse and rat hippocampal neurons].

PMID- 1362512
TI  - Proteinuria and enzymuria in vesicoureteric reflux.
AB  - Vesicoureteric reflux is a common abnormality of the urinary tract leading to
      significant renal morbidity and premature mortality. No reliable non-invasive
      method exists for its diagnosis. This study investigated the presence of urinary
      proteins and enzymes in healthy children and those with reflux. A log normal
      distribution was found for all analyte/creatinine ratios. Significantly higher
      tubular protein/creatinine ratios were found in patients with reflux nephropathy.
      Three enzyme/creatinine ratios (n-acetyl-B-D-glucosaminidase, gamma-glutamyl
      transferase and lactate dehydrogenase) were higher in children with reflux who
      had no renal scarring, but the degree of overlap with the normal range was such
      that it is doubtful whether any will be of use as a urinary marker.

PMID- 1362513
TI  - Testicular cancer and cryptorchidism.
AB  - The records of 273 patients with germ cell tumours of the testis referred between
      1970 and July 1991 were reviewed. There were 25 (9%) black, 40 (14%) mixed race
      and 214 (77%) white patients. Histology showed seminoma in 53% and non
      seminomatous and germ cell tumours in 47% of patients. Maldescent of the testis
      (MDT) was found in 30 patients--an incidence of 11% overall. MDT was present in 8
      of 25 (32%) black, 7 of 40 (18%) mixed race and 15 of 214 (7%) white patients
      with testicular cancer. The incidence of MDT was statistically significantly
      higher in both black and mixed race patients compared with white patients. None
      of the black patients had undergone orchiopexy but 71% of mixed race and 87% of
      white patients had done so. This resulted in a different pattern of presentation
      in black compared with mixed race and white patients with MDT and testicular
      cancer. The mean age was 40 years for black, 32 years for mixed race and 33 years
      for white patients. Black patients presented with abdominal or inguinal tumours
      rather than scrotal tumours and they had an increased tendency to present with
      seminomas.

PMID- 1362514
TI  - Acute testicular torsion following orchidopexy for undescended testis.

PMID- 1362515
TI  - Pylorus-preserving versus standard pancreaticoduodenectomy: an analysis of 110
      pancreatic and periampullary carcinomas.

PMID- 1362516
TI  - Colocalization of peptide- and tyrosine hydroxylase-like immunoreactivities with
      Fos-immunoreactive neurons in rat central amygdaloid nucleus after immobilization
      stress.
AB  - The central amygdaloid nucleus (ACe) is part of the amygdaloid body, and it has
      been shown to participate in several stress related reactions. The ACe is densely
      innervated by tyrosine hydroxylase- (TH), corticotropin releasing factor- (CRF),
      calcitonin gene-related peptide- (CGRP), neurotensin- (NT), somatostatin- (SOM),
      enkephalin- (ENK), substance P- (SP), vasoactive intestinal polypeptide- (VIP)
      and cholecystokinin- (CCK) immunoreactive (IR) nerve terminals. In addition, the
      ACe contains numerous CRF-, NT-, SOM-, ENK- and SP-IR perikarya. In previous
      studies it has been shown that stress stimulates the expression of the immediate
      early gene c-fos in the ACe. The aim of this study was to demonstrate the
      colocalization of the Fos-IR neurons with the peptide- and TH-IR structures using
      an immunocytochemical double staining technique. In intact animals the ACe
      contained only a few Fos-IR neurons. After immobilization stress about 100 Fos-IR
      neurons were seen per section. They were mainly located in the area, which was
      enriched by peptide- and TH-IR nerve terminals. The close contacts observed
      between the Fos-IR neurons and the peptide- and TH-IR nerve endings suggest that
      the Fos-IR neurons were innervated by these nerve terminals. Furthermore, several
      NT-, ENK-, SOM- and CRF-IR neurons were observed and the vast majority of these
      cells exhibited Fos-like immunoreactivity. These results suggest that stress
      enhances the synaptic activity of the ACe, which stimulates the expression of c
      fos. Subsequently, Fos may regulate the expression of the NT, ENK, SOM and CRF
      genes and thus affect the peptidergic efferents from the ACe.

PMID- 1362517
TI  - Postnatal lead exposure induces supersensitivity to the stimulus properties of a
      D2-D3 agonist.
AB  - To examine the impact of lead (Pb) exposure during the ontogeny of dopaminergic
      (DA) systems on resultant DA function, rats were exposed postnatally (0-21 days
      of age) via the lactating dam to 0, 100 or 350 ppm Pb acetate in drinking water.
      At 2 months of age, the postnatally Pb-exposed rats were trained to discriminate
      the stimulus properties of either the D1 receptor agonist SKF38393 (6.0 mg/kg) or
      the D2-D3 receptor family subtype agonist quinpirole (0.05 mg/kg) from saline
      using a standard two-lever operant food-reinforced drug discrimination paradigm.
      In each training group, dose-effect curves describing drug lever responding to
      lower doses of the training drug and to preadministration of selective DA
      antagonists were obtained to examine Pb-induced changes in DA sensitivity, and
      doses of non-DA compounds were substituted to determine the specificity of any
      changes in DA sensitivity. In the D1/saline training condition, Pb exposure was
      not associated with any specific or consistent changes in DA sensitivity. In
      contrast, exposure to Pb was associated with D2-D3 receptor subtype
      supersensitivity as was indicated by significantly elevated levels of drug lever
      responding in the presence of quinpirole and haloperidol and to at least one dose
      of apomorphine. No differences in the dose-effect curves for either (+)
      amphetamine or NMDA were observed in the D2-D3-trained control and Pb-exposed
      groups, but an increase in drug lever responding in the presence of pentobarbital
      was noted in the Pb-exposed group relative to control. Taken together, these
      findings are consistent with a Pb-induced functional D2-D3 supersensitivity
      possibly mediated via autoreceptors. Moreover, this functional D2-D3
      supersensitivity necessarily represents a permanent effect of postnatal Pb
      exposure since both blood and brain Pb levels were negligible at the time drug
      discrimination training began.

PMID- 1362518
TI  - Long-term adaptation of crayfish neurons depends on the frequency and number of
      impulses.
AB  - Increasing the impulse activity of crustacean neurons for a few days causes long
      lasting changes in transmitter release, which are termed 'long-term adaptation'
      (LTA) in previous studies. Both the amount of transmitter released at the
      beginning of a stimulus train, and synaptic fatigue during repetitive
      stimulation, are reduced. The present study examines the dependence of these
      synaptic changes on the frequency and number of impulses used to elicit LTA.
      Fatigue resistance develops consistently when crayfish phasic motor neurons are
      stimulated for 3 days with as few as 9,000 impulses per day, and occurs in
      response either to low frequency stimulation (0.2 or 0.5 Hz), or to stimulation
      in short bursts at a moderate average frequency (2.5 Hz). In contrast, the
      reduction in initial transmitter release does not appear consistently when the
      frequency and number of impulses are both low (9,000 impulses per day delivered
      at 0.2 Hz), but does occur at the moderate stimulus frequency (2.5 Hz) and when a
      larger number of impulses (18,000) are delivered at a low frequency (0.5 Hz). The
      data suggest that the two changes in synaptic transmission that comprise LTA have
      different stimulus requirements.

PMID- 1362519
TI  - Effects of the opiates on the paraventricular nucleus in genetically polydipsic
      mice.
AB  - The inbred mice, STR/N, are known to possess extreme polydipsia with no known
      abnormality in vasopressin system and the kidney function. Our previous studies
      indicate that the opiate antagonists given intracerebroventricularly strongly
      attenuated spontaneous drinking. To determine the site(s) of action, the present
      study was undertaken. Microinjections of naltrexone methobromide and a selective
      kappa-receptor antagonist, nor-binaltorphimine (nor-BNI), into the
      paraventricular nucleus of the hypothalamus (PVN) greatly attenuated drinking of
      the STR/N for 0.5 to 16 h after injections, while in the two control groups, non
      polydipsic STR/1N and Swiss/Webster strains, drinking was not affected by the
      injections. Food intake was not much altered in all groups. Studies of PVN
      neurons in vitro (n = > 160 for each group) showed that basal firing rates and
      patterns were similar in the STR/N and the control groups. Morphine added to the
      medium inhibited some but excited none in all strains tested. The threshold for
      the inhibitory action was higher in the polydipsic STR/N mice (10(-8) M),
      compared to that in the control, S/W mice (10(-9) M). Further, a proportion of
      neurons inhibited by morphine in the PVN was significantly smaller (P < 0.01) in
      the STR/N (41.7%), compared to that in the control (64.9%). Dynorphin had very
      similar effect to that of morphine, but the proportion of cells inhibited was
      25.4% in the STR/N, and 70.4% in the S/W. Prior applications of naloxone to the
      medium prevented the action of both morphine and dynorphin. Under the synaptic
      blockade (in a low Ca2+ and high Mg2+ medium) the inhibitory effect of the
      opiates persisted. We concluded that the PVN is at least one of the possible
      sites where the opiates are acting to cause the polydipsia in the STR/N mice.

PMID- 1362520
TI  - Differential roles of NMDA and non-NMDA receptor activation in induction and
      maintenance of thermal hyperalgesia in rats with painful peripheral
      mononeuropathy.
AB  - Central activation of excitatory amino acid receptors has been implicated in
      neuropathic pain following nerve injury. In a rat model of painful peripheral
      mononeuropathy, we compared the effects of non-competitive NMDA receptor
      antagonists (MK 801 and HA966) and a non-NMDA receptor antagonist (CNQX) on
      induction and maintenance of thermal hyperalgesia induced by chronic constrictive
      injury (CCI) of the rat common sciatic nerve. Thermal hyperalgesia to radiant
      heat was assessed by using a foot-withdrawal test and NMDA/non-NMDA receptor
      antagonists were administered intrathecally onto the lumbar spinal cord before
      and after nerve injury. Four daily single treatments with 20 nmol HA966 or CNQX
      beginning 15 min prior to nerve ligation (pre-injury treatment), reliably reduced
      thermal hyperalgesia in CCI rats on days 3, 5, 7 and 10 after nerve ligation.
      Thermal hyperalgesia was also reduced in CCI rats receiving a single post-injury
      treatment with HA966 (20 or 80 nmol) or MK 801 (5 or 20 nmol) on day 3 after
      nerve ligation when thermal hyperalgesia was well developed. In contrast, a
      single post-injury CNQX (20 or 80 nmol) treatment failed to reduce thermal
      hyperalgesia or to potentiate effects of HA966 or MK 801 (5 or 20 nmol) on
      thermal hyperalgesia in CCI rats. Moreover, multiple post-injury CNQX treatments
      utilizing the same dose regime as employed for the pre-injury treatment
      attenuated thermal hyperalgesia but only when the treatment began 1 or 24 h (but
      not 72 h) after nerve ligation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362521
TI  - MK-801 affects the potassium-induced increase of glial fibrillary acidic protein
      immunoreactivity in rat brain.
AB  - Exposure of a limited brain surface to a high potassium (K+) concentration
      produces an injury limited to the underlying cortex, without apparently affecting
      other brain areas. Such a treatment produces an increased expression of glial
      fibrillary acidic protein (GFAP) in astrocytes, as assessed by
      immunohistochemical techniques, throughout the cortex ipsilateral to K+ exposure.
      This effect is evident 2 days after treatment and persists up to, at least, day
      7. Thirty days after K+ exposure GFAP immunostaining is similar in both
      hemispheres. Administration of the non-competitive NMDA antagonist MK-801 (4
      mg/kg i.p.) prior to the injury prevented the rise in GFAP immunoreactivity (IR)
      at 2 but not 7 days after the treatment. Administration of MK-801 after the
      injury appeared to have no effect on GFAP expression. This work confirms that
      brain injury, associated with spreading depression, can induce a glial response
      far from the lesion site. Furthermore, the fact that this phenomenon can be
      modified by an NMDA receptor antagonist suggests that glutamate may play a role,
      in vivo, in the regulation of astrocytic response to injury and introduces the
      possibility that brain injury-induced gliosis may be pharmacologically
      manipulated.

PMID- 1362522
TI  - The relative importance of reasons for tooth extraction in terms of potential
      tooth years of life lost (PYLL).
AB  - The aim of the present study was to introduce the potential tooth years of life
      lost (PYLL) approach to the analysis of data showing the incidence of tooth
      extraction according to the reason for extraction and to illustrate its use. Six
      sets of data from prospective nationwide questionnaire surveys of patients
      treated by systematic random samples of dentists in five European countries were
      translated into PYLL. Response rates ranged from 25 to 81 per cent and the number
      of extracted teeth from 959 to 29,397, according to the study. PYLL in Norway
      1988 was calculated using the ages of 85 and 80 as cut-off points, or the average
      sex-specific remaining life expectancy at the age of extraction; otherwise the
      age of 85 was used. Mean PYLL for all reasons varied from 40.6 to 46.3 years for
      Norway in 1988 depending on the cut-off point used. For patients aged 21 and
      older PYLL85 ranged from 35.7 years for France in 1984 to 42.3 years for Sweden
      in 1959-61. Employing PYLL changed the rank order of the reasons for extraction
      based on the number of extracted teeth in some instances. It combined the two
      dimensions 'incidence of 'potential years of tooth function lost' into a
      continuous quantitative variable which was easy to understand and simple to
      handle analytically.

PMID- 1362523
TI  - Genetic analysis of the linkage between chromosome 11q and atopy.
AB  - Previous work has suggested that there is a genetic predisposition for the
      development of both asthma and atopy. A recent study has also shown that there is
      a striking link between chromosome 11q and the IgE response underlying asthma and
      rhinitis. To further assess the linkage between chromosome 11q and atopy, we have
      studied nine families of two and, in many instances, three generations with the
      index case having asthma and/or atopy. Using two restriction fragment length
      polymorphism probes associated with the regions 11q12-q13.2, namely PYGM and
      INT2, we have been unable to confirm a significant link between this region of
      chromosome 11q and atopy as defined by a positive skin-prick test and/or a raised
      specific IgE and/or a raised total IgE.

PMID- 1362524
TI  - X-linked polymorphism of hypoxanthine phosphoribosyl transferase gene (HPRT) in
      Chinese females.

PMID- 1362525
TI  - The distribution of type-2 chain histo-blood group antigens in normal cycling
      human endometrium.
AB  - The blood group ABO(H) determinants are major allogenic antigens in both
      erythrocytes and tissue of man. These antigens and related carbohydrates are
      markers of cellular maturation and differentiation in many epithelial tissues and
      have recently attracted great interest as tumor-associated antigens. Previous
      studies of endometrial tissues have indicated that glycosylation in this tissue
      may be related to hormonal stimulation. We have investigated the
      immunohistochemical distribution of type-2 chain histo-blood group-related
      carbohydrates in specimens of normal, cycling endometria obtained from
      hysterectomies on women with known ABO/Lewis erythrocyte type and saliva secretor
      status. N-acetyllactosamine and Le(x) were demonstrated to be uninfluenced by the
      genetic background. A and Ale(y) antigens were exclusively demonstrated in
      endometria from blood group A individuals, while Le(y) was expressed in
      endometria from blood group 0 individuals mainly. The precursor N
      acetyllactosamine as well as the terminal H, A, and ALe(y) antigens were shown in
      only a few cells. In contrast, N-acetyllactosamine substituted by sialic acid
      and/or fucose residues (Le(x), sialosyl-Le(x), Le(y)) were demonstrated in
      epithelial cells of normal, cycling endometrium, but with both quantitative and
      qualitative differences in staining relating to the menstrual cycle, indicating
      that type-2 chain antigens are expressed under both genetic and hormonal
      influence in human cycling endometrium.

PMID- 1362526
TI  - Glutathione and gamma-glutamyl transpeptidase are differentially distributed in
      the olfactory mucosa of rats.
AB  - Components of the gamma-glutamyl cycle, including thiols, glutathione (GSH) and
      gamma-glutamyl transpeptidase (gamma-GT), were localized in the nasal mucosae of
      rats using histochemical and immunohistochemical methods. In olfactory mucosa,
      thiols were widely distributed, with intense staining in the mucociliary complex
      (MC), basal cells, acinar cells of Bowman's glands (BG), and olfactory nerve
      bundles, and with moderate staining in olfactory receptor neurons (ORNs). GSH was
      localized in MC, BG acinar cells, nerve bundles and, to a lesser extent, in ORNs.
      gamma-GT immunoreactivity was restricted to the MC and to basolateral and apical
      membranes of BG acinar and duct cells. The basolateral membrane of BG acinar
      cells, located in close association with blood vessels and connective tissue,
      showed granule-like immunoreactivity. In respiratory mucosa, all three compounds
      were localized in the MC and acinar cells of respiratory glands (RG). In the MC,
      gamma-GT immunoreactivity was associated primarily with brush borders of ciliated
      cells. Granular immunoreactivity was also apparent in the supranuclear region of
      RG acinar cells. These results demonstrate that components of the gamma-glutamyl
      cycle are localized in olfactory and respiratory glands, and that they are
      secreted into the mucus, where they may mediate perireceptor events such as
      detoxification and/or solubilization of air-borne xenobiotics, toxicants and
      odorants.

PMID- 1362528
TI  - StyI polymorphism in an enhancer region of the second intron of the
      apolipoprotein B gene in hyper- and hypocholesterolemic subjects.
AB  - The regulation of the human apolipoprotein (apo) B gene that plays a crucial role
      in lipid metabolism is apparently very complex, with multiple cis- and trans
      acting regulatory factors. One of these factors is an enhancer region in the
      second intron. In this region a point mutation at position + 722 has been found
      that is detectable by the restriction enzyme StyI. The report of Levy-Wilson et
      al. (1991) could suggest that the mutant allele (abolished StyI site) is
      associated with hypocholesterolemia. To investigate further the possible effect
      of this mutation on plasma cholesterol levels, we have compared the frequency of
      the mutant allele between 206 hypercholesterolemic Norwegian or Czech subjects on
      one hand, and 165 hypocholesterolemic Norwegian or Czech subjects on the other
      hand. No significant difference in frequency was found between the
      hypercholesterolemic and the hypocholesterolemic groups. This finding indicates
      either that the mutation at position + 722 does not affect the enhancer activity
      or that this in vitro enhancer activity is of little or no clinical significance.
      One of the Norwegian hypercholesterolemic subjects who was of Czech descent
      possessed the apoB 3500 mutation that leads to defective binding of low density
      lipoprotein (LDL) to the LDL receptors. Haplotype analysis of the apoB gene in
      her family showed that the mutation-bearing allele was identical to that reported
      in other countries, indicating a common gene source.

PMID- 1362529
TI  - beta-Thalassaemia mutations and their linkage to beta-haplotypes in Tamil Nadu in
      southern India.
AB  - A study for screening of beta-thalassaemia mutations by the Amplification
      Refractory Mutation System (ARMS) and haplotyping by Polymerase Chain Reaction
      (PCR) was undertaken because there was a paucity of data in Tamil Nadu in
      Southern India and to initiate a comprehensive prenatal diagnosis programme. A
      total of 294 alleles were analysed to study the nature of the mutations, of which
      146 were beta-thalassaemia alleles. Only four types of beta-thalassaemia
      mutations were recorded. Of these, 128 alleles were of the variant IVS-1 nt 5 (G-
      >C). Thirteen had the mutation codon 41/42 (del TCTT), four had the mutation
      codon 8/9 (insert G) and one had the 619 bp deletion at the 3' end of the gene.
      The most common mutation, IVS-1 nt 5 (G-->C), was strongly associated with a
      single haplotype although the association was not absolute. The population of
      Tamil Nadu in Southern India seems to be ideal for initiating a prenatal
      diagnosis programme based on direct detection of mutation by ARMS coupled with
      RFLP linkage analysis.

PMID- 1362527
TI  - Sex steroids do not alter sex differences in tyrosine hydroxylase activity of
      dopaminergic neurons in vitro.
AB  - In order to distinguish the effects of genetic sex from those of sex hormones on
      the sexual differentiation of dopaminergic neurons, catecholamine synthesis was
      studied in gender-specific cultures of embryonic day-14 rat diencephalon. In
      addition to embryos from normal dams, embryos were used whose mothers had been
      treated with the estrogen antagonist tamoxifen or the testosterone antagonist
      cyproterone acetate on days 12 and 13 of gestation. Cultures from embryos of
      untreated dams were fed daily with a medium containing 17 beta-estradiol or
      testosterone. After 10 days in vitro, cultures were immunostained for tyrosine
      hydroxylase and the accumulation of dihydroxyphenylalanine (DOPA) was measured in
      the presence of the DOPA decarboxylase inhibitor NSD 1015. Rates of DOPA
      synthesis, unlike the numbers of tyrosine hydroxylase-immunoreactive neurons,
      were markedly higher in female cultures under all experimental conditions.
      Treatment of dams with antisteroids prior to removal of the embryos had no
      influence on these results. Treatment of cultures with both steroids decreased
      DOPA formation in a dose-dependent manner without altering the sex difference.
      These results suggest that cultured diencephalic dopaminergic neurons develop sex
      differences in the activity of tyrosine hydroxylase. This sexual dimorphism is
      initiated independently on the activity of gonadal steroid hormones. Sex hormones
      exert an additional modulatory influence on the activity of the enzyme but do not
      abolish or reverse sex differences. Therefore, the concept of a purely epigenetic
      mode of sexual differentiation of the mammalian brain needs to be broadened to
      incorporate other mechanisms, such as the cell-autonomous fulfillment of a sex
      specific genetic program.

PMID- 1362530
TI  - Analysis of three glucose transporter genes in a Caucasian population: no
      associations with non-insulin-dependent diabetes and obesity.
AB  - The significance of variation within the genes coding for three glucose
      transporter proteins in the aetiology of non-insulin dependent diabetes mellitus
      was assessed by analysing restriction fragment length polymorphisms in an English
      Caucasian population. Two polymorphisms at the HepG2/erythrocyte glucose
      transporter (GLUT1) locus, four at the liver/pancreatic glucose transporter
      (GLUT2) locus and one at the muscle/adipocyte glucose transporter (GLUT4) were
      analysed in a sample of diabetic and non-diabetic subjects. No significant
      differences in the allelic, genotypic or haplotypic frequencies of the
      polymorphisms at these three loci were observed between the diabetic or non
      diabetic populations. No significant linkage disequilibrium was observed between
      the two GLUT1 polymorphic sites, whereas the four polymorphic sites at the GLUT2
      locus, one of which appears to be due to a 100-200 base pair DNA
      insertion/deletion, were found to be in significant linkage disequilibrium. In
      order to study the possible role of glucose transporter gene variants
      contributing to the development of obesity, the body mass indexes were compared
      in the different genotypic groups of diabetic and non-diabetic subjects. No
      differences in body mass index between genotype groups were found at the p <
      0.005 level of significance.

PMID- 1362531
TI  - The three week sulphasalazine syndrome.
AB  - We report a 53-year-old man with sero-negative rheumatoid arthritis who developed
      a fever, rash and hepatitis 3 weeks after starting sulphasalazine therapy. This
      was associated with a T cell lymphocytosis, eosinophilia and evidence of
      classical complement pathway activation. He responded to high dose
      corticosteroids. This is a rare but characteristic reaction which is likely to be
      encountered by rheumatologists more frequently with the increasing use of
      sulphasalazine. It should be recognized promptly as it may be fatal and can be
      confused with other systemic diseases.

PMID- 1362532
TI  - Report of the second international workshop on human chromosome 5 mapping.

PMID- 1362533
TI  - Report of the second international workshop on human chromosome 5 mapping:
      consensus genetic map.

PMID- 1362535
TI  - Neuropsychology of Partial Epilepsy. Proceedings of an International Symposium.
      Bologna, Italy, May 18, 1991.

PMID- 1362534
TI  - Report of the first international workshop on human chromosome 12 mapping.

PMID- 1362536
TI  - Biomonitoring and Susceptibility Markers in Human Cancer: Applications in
      Molecular Epidemiology and Risk Assessment. Proceedings of a symposium. Kailua
      Kona, Hawaii, October 16-November 1, 1991.

PMID- 1362537
TI  - The debrisoquine metabolic phenotype and DNA-based assays: implications of
      misclassification for the association of lung cancer and the debrisoquine
      metabolic phenotype.
AB  - Debrisoquine is an antihypertensive drug that is metabolized by cytochrome
      P4502D6. Deficient metabolism is inherited as an autosomal recessive condition.
      We previously reported in a case-control study that extensive metabolizers of
      debrisoquine were at greater risk of lung cancer compared to poor and
      intermediate metabolizers. Cloning of the gene that encodes P4502D6 (CYP2D6) led
      to the identification of both wild-type and mutant forms of the gene.
      Subsequently, a DNA-restriction fragment length polymorphism (RFLP) was
      identified, and a Southern hybridization-based test was developed in an attempt
      to define the genotype. When the DNA-RFLP test was applied to stored DNA from our
      study subjects there was neither a significant association with the metabolic
      phenotype nor an association with lung cancer. Further work has demonstrated that
      the wild-type gene, which was characterized by a 29-kb allele, can also contain
      mutations that result in nonfunctional or absent proteins. When these mutations
      are present, individuals exhibit the poor or intermediate metabolizer phenotype
      in spite of the presence of the 29-kb putative wild-type allele. Sequence
      determination of the mutants led to the development of techniques to exploit the
      polymerase chain reaction, which, together with Southern analysis, have been
      reported to detect as many as 95% of poor metabolizers. This technique is being
      used to examine the association of the extensive metabolizer genotype with lung
      cancer in the subjects from the case-control study. Preliminary results indicate
      a weak association between the homozygous wild-type genotype and lung cancer; in
      contrast, the extensive metabolizer phenotype is strongly associated with lung
      cancer in this subset.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362538
TI  - Allele diversity of the H-ras-1 variable number of tandem repeats in Norwegian
      lung cancer patients.
AB  - We have examined restriction fragment length polymorphisms of the H-ras-1 gene in
      germ-line DNA from 214 lung cancer patients and 309 unaffected controls. When DNA
      samples were digested with MspI/HpaII, Southern blot analysis revealed at least
      22 different alleles, grouped according to their frequencies as common,
      intermediate, and rare. The frequency of rare alleles in lung cancer patients
      (16/428) is significantly different (p = 0.002) from that in the control group
      (5/618). Individuals with rare alleles were found to be at 4.7-fold greater risk
      of lung cancer than those with no rare alleles.

PMID- 1362539
TI  - Polycyclic aromatic hydrocarbon-DNA adducts and the CYP1A1 restriction fragment
      length polymorphism.
AB  - Human cancer risk assessment at a genetic level involves the investigation of
      carcinogen metabolism and DNA adduct formation. Wide interindividual differences
      in metabolism result in different DNA adduct levels. For this and other reasons,
      many laboratories have considered DNA adducts to be a measure of the biologically
      effective dose of a carcinogen. Techniques for studying DNA adducts using
      chemically specific assays are becoming available. A modification of the 32P
      postlabeling assay for polycyclic aromatic hydrocarbon DNA adducts described here
      provides potential improvements in quantification. DNA adducts, however, reflect
      only recent exposure to carcinogens; in contrast, genetic testing for metabolic
      capacity indicates the extent to which carcinogens can be activated and exert
      genotoxic effects. Such studies may reflect both separate and integrated risk
      factors together with DNA adduct levels. A recently described restriction
      fragment length polymorphism for the CYP1A1, which codes for the cytochrome P450
      enzyme primarily responsible for the metabolic activation of carcinogenic
      polycyclic aromatic hydrocarbons, has been found to be associated with lung
      cancer risk in a Japanese population. In a subset of individuals enrolled in a
      U.S. lung cancer case-control study, no association with lung cancer was found.

PMID- 1362541
TI  - Diuretics--past, present and future prospects in cardiovascular disease.
      Proceedings of a seminar. Quinta do Lago, Portugal, 13-14 March 1992.

PMID- 1362540
TI  - Emergence during unsuccessful chemotherapy of multiple drug resistance in a
      strain of Mycobacterium tuberculosis.
AB  - Serial isolates of Mycobacterium tuberculosis were cultured from a patient who
      failed to respond to standard antituberculous chemotherapy. Isolates were
      cultured in March 1989, July 1989, December 1989 and May 1990. Each successive
      isolate was found to be resistant to a wider range of antituberculous drugs than
      its predecessors. The initial isolate was resistant to isoniazid and rifampin,
      the second isolate was also resistant to ethambutol, the third was also resistant
      to pyrazinamide, ansamycin (= rifabutin) and ofloxacin and the last isolate was
      also resistant to ciprofloxacin and sparfloxacin. All four isolates'
      bacteriophage typing profiles and DNA restriction fragment patterns determined by
      Southern blot hybridization using the IS6110/IS986 probes and the new probe
      pTBN12 were concordant. It was concluded that this patient was persistently
      infected with a single strain of Mycobacterium tuberculosis which developed
      resistance to a number of families of drugs but did not show any significant
      change in typing patterns. The problem of acquired multiple drug resistance,
      particularly to fluoroquinolones and rifamycins, represents a new challenge in
      tuberculosis therapy.

PMID- 1362542
TI  - Where now the diuretics in antihypertensive treatment?
AB  - The ultimate aim in treating hypertension is to reduce cardiovascular mortality
      and morbidity, especially from coronary heart disease and strokes. In several
      long-term trials this goal has been achieved with antihypertensive therapy in the
      form of diuretics. Subsequently, diuretics and betablockers, compared as single
      agents or with the addition of other agents, did not appear to affect overall
      cardiovascular morbidity and mortality differentially. Therefore, recommended
      first-line therapy for hypertension was initially diuretics, followed later by
      beta blockers as alternatives. Recently, calcium antagonists and ACE inhibitors
      have been accepted as equally valuable in the treatment of hypertension because
      they similarly lower blood pressure, lack any adverse metabolic effects and may
      be more beneficial than diuretics or beta-blockers on the long-term prognosis of
      hypertensive patients. Such recommendations are, however, highly speculative and
      are not supported by trials using cardiovascular mortality and morbidity as
      endpoints. In order to solve the conflict between proven facts and sound theory,
      long-term trials comparing older (mainly diuretics) and newer (calcium
      antagonists, ACE inhibitors, alpha-adrenoceptor blockers) antihypertensive agents
      are needed. Until such trials are completed, the debate surrounding first-line
      drugs for antihypertensive treatment will not be resolved.

PMID- 1362543
TI  - Neurohormonal consequences of diuretics in different cardiovascular syndromes.
AB  - Diuretics have long been used to lower blood pressure in hypertensive patients or
      to control body fluid and electrolyte homeostasis in diseases such as congestive
      heart failure, chronic renal failure or cirrhosis. The initial response to
      diuretics is a negative sodium and fluid balance. The diuretic-induced loss of
      salt and water activates several hormonal systems such as vasopressin, the renin
      angiotensin-aldosterone system or the sympathetic nervous system which tend to
      compensate for the changes in sodium and water balance. This neurohormonal
      response may have important clinical implications. Thus, the activation of the
      renin-angiotensin-aldosterone cascade appears to be partially responsible for the
      flat dose-blood pressure response curve of thiazides in hypertensive patients. It
      may also be responsible for the difference between responders and non-responders
      to diuretic therapy and for the development of side-effects such as hypokalaemia,
      metabolic alkalosis or hyponatraemia. There are several ways to prevent the
      undesirable consequences of the neurohormonal responses to diuretics. The first
      is to use low doses of these agents. It is also possible to combine them with
      agents that block the activity of the renin-angiotensin-aldosterone system such
      as ACE inhibitors or in combination with drugs that reduce aldosterone secretion
      such as calcium antagonists. The development of drugs able to enhance urinary
      sodium excretion and to reduce simultaneously the activity of the renin
      angiotensin-aldosterone system may offer a new interesting alternative. This
      might perhaps be achieved in the future with the administration of neutral
      endopeptidase inhibitors which interfere with the enzymatic degradation of atrial
      natriuretic peptide.

PMID- 1362546
TI  - Dipeptidylpeptidase IV initiates the degradation of neuropeptide Y in cardiac
      muscle membranes.

PMID- 1362545
TI  - The effect of alpha blockade on cholesterol regulation in vitro and in vivo.

PMID- 1362547
TI  - C1300 neuroblastoma cells possess quisqualate sensitive glutamate binding sites.

PMID- 1362544
TI  - Inhibitory effects of excitatory amino acids on pyramidal cells of the in vitro
      turtle medial cortex.
AB  - The electroencephalogram of the in vitro brain of the turtle Chrysemys d' orbigny
      shows spontaneous random large sharp waves (LSWs) which may be compared to
      interictal spikes. In order to evaluate the role of excitatory amino acids (EAAs)
      -in particular through the N-methyl-D-aspartate (NMDA) receptor--in the
      generation of LSWs, the bath application of NMDA and its antagonists 3-((+/-)-2
      carboxypiperazin-4y)-propyl-1-phosphonic acid (CPP) and DL-2-amino-5
      phosphonovaleric acid (APV), was performed in the whole open hemisphere (WOH) in
      vitro. Field recordings in WOH showed that both CPP and APV unexpectedly
      increased LSW amplitude. Consistently, NMDA in the bath suppressed the LSWs.
      Iontophoretically applied glutamate, kainate and NMDA produced a
      hyperpolarization of intracellularly recorded medial cortex pyramidal cells both
      in WOH and in slices. The EAA-induced hyperpolarization was tetrodotoxin (TTX)
      and bicuculline sensitive and reversed close to -70 mV. It would therefore seem
      to be due to the activation of gamma-aminobutyric acid (GABA) interneurons. The
      NMDA could also produce an excitation of pyramidal cells--always following a
      previous inhibitory phase. In some cases rhythmic bursting discharges or plateau
      potentials were observed. These NMDA effects were mainly elicited by a direct
      effect on pyramidal cells. A long-lasting hyperpolarizing response following the
      NMDA excitatory phase was also observed. This long-lasting response was an
      intrinsic property of pyramidal cells since it was TTX resistant. This study
      demonstrates that GABAergic interneurons from the turtle medial cortex can be
      activated by EAAs, a mechanism that can account for the effects of NMDA
      antagonists on LSWs.

PMID- 1362548
TI  - Purine nucleotide content in human T4 and T8 lymphocyte subpopulations from
      normal subjects and AIDS patients.

PMID- 1362549
TI  - Morphological analysis of the regulation of CD4 endocytosis by p56lck.

PMID- 1362550
TI  - The action of the psychoactive drug 2C-B on isolated rat thoracic aorta.
AB  - 1. 2C-B [2-(4-bromo-2,5-dimethoxyphenyl)ethylamine] elicits concentration
      dependent contraction of the rat thoracic aorta (apparent pD2 = 4.55). The
      maximal contraction (Emax) attained with 2C-B is less than that produced by
      either norepinephrine (NE) or serotonin (5-HT). 2. Pretreatment with either
      prazosin (5 x 10(-9) - 10(-8) M) or ketanserin (5 x 10(-9) - 10(-8) M) leads to
      decreased slopes and Emax in the 2C-B dose-response curves. 3. 2.82 x 10(-5) M 2C
      B potentiates the response to low concentrations of NE; 5 x 10(-5) M 2C-B shows
      similar behaviour, but with reduced Emax. At 10(-6) M 2C-B acts as a competitive
      5-HT antagonist; at 2.8 x 10(-5) M, however, it behaves like a non-competitive 5
      HT antagonist. 4. Removal of the endothelial lining from the aortal rings only
      shifts the 2C-B dose-response curve to the left. 5. These results suggest that 2C
      B behaves as a partial agonist toward both alpha 1-adrenergic and 5-HT2
      serotonergic receptors. The endothelium only seems to act as a diffusional
      barrier to the drug.

PMID- 1362551
TI  - Mechanisms of L-NG-nitro arginine methyl ester-induced antinociception in mice: a
      role for serotonergic and adrenergic neurons.
AB  - 1. The mechanisms involved in the antinociceptive action of L-NG-nitro arginine
      methyl ester (L-NAME) were investigated in mice. 2. Intraperitoneal
      administration of L-NAME produced a dose-dependent antinociception in the tail
      flick, hot-plate and phenyl-p-quinone-induced writhing tests. 3. Pretreatment
      with the catecholamine depletors 6-hydroxydopamine (5 micrograms i.c.v.) or
      reserpine (5 mg/kg i.p.) or the serotonin synthesis inhibitor, p
      chlorophenylalanine methyl ester (200 mg/kg i.p. on 2 consecutive days) resulted
      in a significant decrease in the antinociceptive effect of L-NAME. 4. Similarly,
      pretreatment with the selective alpha 1-adrenoceptor antagonist prazonin (2.5
      mg/kg, i.p.), or the non-selective alpha-adrenoceptor blocker, phentolamine (5
      mg/kg, i.p.) antagonized the antinociceptive effect of L-NAME. 5. However, the
      administration of the selective alpha 2-adrenoceptor antagonist, idazoxan (2.5
      mg/kg i.p.) was without effect. 6. Likewise, pretreatment with the serotonin 5
      HT2 receptor blocker, ketanserin (1 mg/kg, i.p.), the D2 dopamine receptor
      antagonist (+/-) sulpiride (30 mg/kg, i.p.) or the opioid antagonist naloxone (5
      mg/kg, i.p.) did not inhibit the antinociceptive effect of L-NAME. 7. These
      results suggest that L-NAME produces antinociception in the mouse probably by an
      action on adrenergic and serotonergic synapses.

PMID- 1362553
TI  - Neural mechanisms of general anaesthesia. Proceedings of a symposium at the
      Society for Experimental Biology meeting. Birmingham, April 1991.

PMID- 1362552
TI  - Morphine stimulates locomotor activity by an indirect dopaminergic mechanism:
      possible D-1 and D-2 receptor involvement.
AB  - 1. The effect of morphine on locomotor activity in mice and the mechanism
      involved were evaluated. 2. Subcutaneous (s.c.) injection of different doses of
      morphine (10, 20 and 40 mg kg-1) into mice induced a dose-dependent locomotor
      activity. 3. The response to morphine was decreased in animals pretreated by the
      D-1 antagonist SCH 23390, the D-2 antagonist sulpiride or the opiate receptor
      antagonist naloxone, but not by atropine, phenoxybenzamine, propranolol and
      methergoline. 4. The inhibitory effects of SCH 23390, sulpiride or naloxone were
      dose-dependent. 5. Pretreatment with reserpine prevented the effect of morphine.
      SKF 38393 (D-1 agonist) or quinpirole (D-2 agonist) also induced locomotor
      activity in mice. Also this effect was decreased by reserpine pretreatment. 6.
      Combination of SKF 38393 with quinpirole but not of morphine with SKF 38393 or
      quinpirole induced a high degree of locomotor activity in intact and reserpinized
      animals. 7. It is concluded that locomotor activity induced by morphine is
      mediated by opiate receptor through an indirect dopaminergic mechanism.

PMID- 1362555
TI  - [2nd National Enantone-Gyn Symposium. GnRH-Analogs in Gynecology. Berlin, 12
      September 1992].

PMID- 1362554
TI  - Anti-CD2 and anti-CD3 induced T cell cytotoxicity of human intraepithelial and
      lamina propria lymphocytes.
AB  - The effector function of immunocompetent cells in the gut mucosa has not yet been
      defined. The cytotoxic function of these cells might be important in the normal
      immune response and could be relevant to the mucosal damage seen in inflammatory
      conditions. The cytotoxic function of isolated intraepithelial and lamina propria
      mononuclear cells in six and 18 hour assays after the addition of various stimuli
      that interact with the human leukocyte antigens CD2 and CD3 on the mucosal
      effector cells was investigated. T cell phenotypes were determined using CD4,
      CD8, and HML1 to characterise cells of the appropriate compartments. Anti-CD3 and
      phytohaemagglutinin can induce toxic activity of lamina propria lymphocytes in
      most individuals after six hours and in all individuals after 18 hours. Anti-CD2,
      anti-CD3, and phytohaemagglutinin are similarly effective at triggering lamina
      propria lymphocytes. Intraepithelial lymphocytes contain predominantly CD8 and
      HML1 positive T cells, differentiating phenotypically intraepithelial lymphocytes
      from lamina propria lymphocytes. Intraepithelial lymphocytes are not cytotoxic at
      six hours, but have a toxic function comparable with lamina propria lymphocytes
      after 18 hours with all three triggers. Intraepithelial lymphocytes from inflamed
      mucosa (Crohn's disease and diverticulitis) mediate significantly reduced
      cytotoxicity in vitro compared with normal mucosa, whereas lamina propria
      lymphocyte toxicity is not different. Reduced numbers of cytotoxic cells and
      reduced reactivity to the trigger substances used after in vivo activation or
      cold target inhibition could explain the observed differences between
      intraepithelial lymphocytes from inflamed and uninflamed mucosa. Changes in cell
      mediated cytotoxicity of intraepithelial lymphocytes and lamina propria
      lymphocytes may be involved in the mucosal damage in these inflammatory
      conditions.

PMID- 1362556
TI  - The effects of acute and repeated doses of suriclone on subjective sleep,
      psychomotor performance and cognitive function in young and elderly volunteers.
AB  - Suriclone is a new anxiolytic drug belonging to the family of cyclopyrrolones.
      The effects of acute and repeated doses of suriclone on subjective sleep,
      psychomotor performance and cognitive function were compared to those of placebo
      in young and elderly volunteers. Young volunteers randomly received suriclone 0.2
      mg, 0.3 mg, 0.4 mg or placebo tid, and the elderly received suriclone 0.1 mg, 0.2
      mg or placebo tid. After the first single dose and after a three-day treatment,
      subjects completed at 1, 2, 4, 12 and 24 h after drug administration the
      following battery of psychomotor and cognitive tests: critical flicker fusion
      threshold, choice reaction time, simulated car tracking test, the stroop test and
      the Sternberg memory scanning task. Visual analogue scales and the Leeds sleep
      evaluation questionnaire were also administered during the study. No significant
      effects of suriclone compared to placebo were seen on the psychomotor tests both
      in young and elderly volunteers. The only significant result was an improvement
      of the ease of getting to sleep in the young with 0.4 mg suriclone tid. In
      conclusion, there is little evidence to suggest that suriclone produces any
      measurable behavioural toxicity, so often seen with many of the benzodiazepines,
      in either young or elderly subjects.

PMID- 1362557
TI  - Identification of TaqI polymorphism in the mitochondrial acetoacetyl-CoA thiolase
      gene and familial analysis of 3-ketothiolase deficiency.
AB  - We analyzed the mitochondrial acetoacetyl-CoA thiolase gene (T2) by Southern
      blotting. Fifteen unrelated healthy individuals and members of five families with
      3-ketothiolase deficiency (3KTD) were analyzed. We found a TaqI polymorphism, the
      heterozygosity of which was calculated to be 0.5 among healthy Japanese
      individuals. This restriction fragment length polymorphism (RFLP) proved to be
      useful for detecting 3KTD patients and its obligatory carriers, at the DNA level
      and in two out of five 3KTD families. This polymorphism was found to be generated
      by the presence/absence of a TaqI site in intron 9 of the T2 gene. With in vitro
      amplification of the genomic region around the TaqI site, this RFLP can be
      detected within 2 days.

PMID- 1362558
TI  - Linkage to Xq28 in a family with nonspecific X-linked mental retardation.
AB  - Linkage analysis was performed in a family with nonspecific X-linked mental
      retardation (MRX). Affected individuals had no clinical characteristics other
      than mental retardation. Linkage was detected to the marker loci DXS477, DXS465,
      DXS52, DXS15 and F8C with maximum lod scores of 1.70, 1.32, 2.52, 1.70, and 1.09,
      respectively (theta = 0.0). The results strongly indicate that the gene for
      mental retardation in the family studied maps close to DXS52.

PMID- 1362559
TI  - A family with X-linked deafness showing linkage to the proximal Xq region of the
      X chromosome.
AB  - Linkage analysis has been carried out in a family with severe congenital
      sensorineural deafness with a structural abnormality of the inner ear.
      Recombinations show the gene responsible for deafness in this family to lie
      between the loci DXS255 (Xp11.22) and DXS94 (Xq22). Close linkage was found to
      locus DXS159 (cpX289) in Xq12, with a LOD score of 3.155 and 0 recombination.
      This location is consistent with other linkage studies of X-linked deafness.

PMID- 1362560
TI  - BglII RFLP in DXS 498 between the pigment gene repeat unit, RCP and GCP.
AB  - The red (RCP) and green (GCP) color pigment genes are located in Xq28, a
      chromosomal region implicated in many genetic disorders. The restriction fragment
      length polymorphism (RFLP) we describe here will be useful for linkage analysis
      in these disorders.

PMID- 1362561
TI  - Detection of a new polymorphism of the human prothrombin (F2) gene by combination
      of PASA and mutated primer-mediated PCR-RFLP.
AB  - A new polymorphism of the human prothrombin (F2) gene was detected by a
      combination of polymerase chain reaction (PCR) amplification of specific alleles
      (PASA) and mutated primer-mediated PCR restriction fragment length polymorphism
      (PCR-RFLP). The method is simple and useful for detecting polymorphisms and
      mutations. The new polymorphism of C1 and C2 examined by this method is highly
      heterozygous and serves as a good human DNA marker.

PMID- 1362562
TI  - PCR detection of two RFLPs in exon I of the alpha-L-iduronidase (IDUA) gene.
AB  - Two polymorphisms were detected within exon I of the alpha-L-iduronidase (IDUA)
      gene both of which create restriction endonuclease sites and one of which changes
      an amino acid. The polymorphisms may be detected by digesting the same 245-bp
      polymerase chain reaction product. The polymorphisms can be used diagnostically
      in families with IDUA deficiency (mucopolysaccharidosis type I) and Huntington
      disease, which is closely linked to the IDUA locus.

PMID- 1362563
TI  - 44th Annual Conference of the Cardiological Society of India. New Delhi, November
      3-5, 1992. Abstracts.

PMID- 1362564
TI  - A rare TaqI polymorphism in a human complement C4 gene is caused by an additional
      restriction site in the first intron.
AB  - We studied the configuration of the complement C4/CYP21 (steroid 21-hydroxylase)
      region of the human major histocompatibility complex in patients suffering from
      congenital adrenal hyperplasia (CAH) and in the general population in The
      Netherlands, using C4 and CYP21 probes and the restriction enzymes TaqI and
      Bg/II. We found a rare TaqI 3.9-kb restriction fragment in the mother of a CAH
      patient, and present evidence that this polymorphism is caused by an additional
      restriction site in the first intron of a complement C4 gene.

PMID- 1362565
TI  - Antigen presentation by murine splenic, but not hepatic, antigen-presenting cells
      to induce IL-2/IL-4 production from immune T cells is regulated by interactions
      between LFA-1/ICAM-1.
AB  - Pretransplant transfusion of multiple minor histoincompatible spleen cells to
      naive recipient mice by the portal vein suppresses the ability of those animals
      to reject skin grafts from mice syngeneic with those used for transfusion, and
      decreases in vitro immunity on rechallenge with the same antigens, by comparison
      with mice receiving transfusion by the lateral tail vein. We have shown elsewhere
      that this is correlated with a diminished activation of Th1 cells for IL-2
      production, without apparently affecting activation of Th2 cells for IL-4
      production. Similar data are obtained by merely infusing hepatic (vs. splenic)
      antigen-presenting cells (APC) into normal mice, or by challenging immune cells
      in vitro with antigen-pulsed hepatic (vs. splenic) APC. However, when antigen
      pulsed splenic APC are incubated with immune T cells in the presence of anti-LFA
      1 monoclonal antibody (Mab), selective activation of Th2 cells (as is seen with
      hepatic APC) again occurs at the expense of activation of Th1 cells. Anti-LFA-1
      Mab causes little perturbation in lymphokine production from T cells stimulated
      with hepatic APC. Using cDNA probes for IL-2 and IL-4 we show that T-cell
      activation in the presence of anti-LFA-1 Mab leads to selective inhibition of
      transcription of IL-2 mRNA.

PMID- 1362566
TI  - Epstein-Barr virus-induced transformation of human B lymphocytes: the effect of L
      leucyl-L-leucine methyl ester on inhibitory T cell populations.
AB  - Epstein-Barr virus-mediated transformation of human B lymphocytes is inhibited by
      human T lymphocytes as well as by interferon-gamma. Removal of the inhibitory
      cell populations is essential in order to achieve successful transformation in
      vitro. Cells with the capacity to inhibit outgrowth of lymphoblastoid cell lines
      can be removed by pretreatment of peripheral blood mononuclear cells with L
      leucyl-L-leucine methyl ester. This treatment eliminates monocytes, NK-cells and
      a CD8+ T cell subpopulation. We now show that such treatment also has toxic
      effects on other human T cell populations. In addition, CD4+ and/or CD8+
      lymphocytes are demonstrated to contain effector cell activities which inhibit
      outgrowth of EBV-transformed B cells. This inhibitory activity is abolished after
      treatment of peripheral blood mononuclear cells or purified CD4+ T cells with L
      leucyl-L-leucine methyl ester. No evidence was found for a selective toxicity
      against any subset within the CD4+ or CD8+ T cell populations. However, the
      capacity of the treated cells, both peripheral blood mononuclear cells and
      purified CD4+ T lymphocytes, to produce mRNA encoding IFN-gamma, a protein
      previously shown to downregulate outgrowth of EBV-transformed B cells, was
      selectively impaired. The results obtained suggest a role for CD4+ T cells to
      inhibit EBV-induced transformation of B cells.

PMID- 1362567
TI  - Characterization and modulation of cell surface proteases on human myeloblastic
      (HL-60) cells and comparison to normal myeloid cells.
AB  - Human myeloblastic HL-60 cells were probed for cell surface protease activity. A
      class of bestatin sensitive N-exoaminopeptidases and a dipeptidyl aminopeptidase
      IV-like enzyme specifically inhibited by DFP and diprotin A were detected at the
      surface of intact cells, as well as in highly purified HL-60 cell membranes. Cell
      surface proteolytic activities were investigated in HL-60 cells induced to
      differentiate into granulocytes or macrophages as well as on normal human myeloid
      cells. It was found that membrane expression of serine and N-aminopeptidases
      significantly increased following maturation of the HL-60 cell line and normal
      monocytes toward the macrophage pathway. In contrast, N-aminopeptidase expression
      was mainly down-regulated on HL-60 cells differentiated into granulocytes and low
      activity was paralleled with that expressed by normal blood granulocytes. HL-60
      maturation into the granulocyte lineage however did not cause any modulation in
      membrane DPP IV-like enzyme. Thus, selective expression of cell surface proteases
      along the myeloid lineage provides a useful model system for determining the
      possible influence of such enzymes on normal and malignant myeloid cells.

PMID- 1362568
TI  - Taxol administered as a 120 hour infusion.
AB  - A Phase I trial of Taxol administered as a 120 h infusion once every 3 weeks was
      conducted in 20 patients with advanced cancer. The initial dose was 5 mg/m2/d (25
      mg/m2 total dose) and patients received 10 mg/m2/d, 25 mg/m2/d, 30 mg/m2/d and 36
      mg/m2/d. Forty-four courses of taxol were administered and all patients were
      evaluable for toxicity. Grade 4 leukopenia was the dose limiting toxicity
      observed in 50% of patients treated with 36 mg/m2/d. Significant mucositis was
      also observed at 30 and 36 mg/m2/d. All toxicity resolved within three weeks of
      treatment and no cumulative toxicity was observed. No neurotoxicity or
      cardiotoxicity was observed and no episodes of hypersensitivity reaction were
      noted. We conclude that 30 mg/m2/d is an appropriate dose for phase II testing of
      this schedule.

PMID- 1362569
TI  - Depot neuroleptic therapy: an underutilized treatment option.
AB  - BACKGROUND: Depot neuroleptics are effective as long-term maintenance therapy in
      chronic schizophrenia and are widely used in Europe. In the United States,
      however, physicians have been reluctant to use them. They assume that depot
      neuroleptics present an increased risk of major side effects, that patients do
      not accept or tolerate them as well as oral agents, and that prescribing depot
      neuroleptics increases the possibility of medicolegal problems. METHOD: We
      analyzed the published data on neuroleptic malignant syndrome, tardive
      dyskinesia, extrapyramidal symptoms, perceptions of depot therapy, and
      medicolegal concerns. Whenever possible, we used the Mantel-Haenszel test to
      compare the outcome of oral versus depot neuroleptic medication treatment.
      RESULTS: Depot neuroleptics are not associated with an increase in any of the
      negative outcomes assessed. CONCLUSION: Depot neuroleptics represent a valuable
      treatment option for many patients and merit wider use.

PMID- 1362570
TI  - The Use of Benzodiazepine Hypnotics: A Scientific Examination of a Clinical
      Controversy. Proceedings of a roundtable symposium. Phoenix, Arizona, April 10,
      1992.

PMID- 1362572
TI  - Bio-Chromatography and Molecular Biology. Proceedings of the 4th European Meeting
      of the Groupe Francais de Bio-Chromatographie. Herault, France, May 12-14, 1992.

PMID- 1362571
TI  - Occurrence of brown adipocytes in rat white adipose tissue: molecular and
      morphological characterization.
AB  - Brown adipocytes are thermogenic cells which play an important role in energy
      balance. Their thermogenic activity is due to the presence of a mitochondrial
      uncoupling protein (UCP). Until recently, it was admitted that in rodents brown
      adipocytes were mainly located in classical brown adipose tissue (BAT). In the
      present study, we have investigated the presence of UCP protein or mRNA in white
      adipose tissue (WAT) of rats. Using polymerase chain reaction or Northern blot
      hybridization, UCP mRNA was detected in mesenteric, epidydimal, retroperitoneal,
      inguinal and particularly in periovarian adipose depots. The uncoupling protein
      was detected by Western blotting in mitochondria from periovarian adipose tissue.
      When rats were submitted to cold or to treatment with a beta-adrenoceptor
      agonist, UCP expression was increased in this tissue as in typical brown fat.
      Moreover, the expression was decreased in obese fa/fa rats compared to lean
      controls. Morphological studies showed that periovarian adipose tissue of rats
      kept at 24 degrees C contained cells with numerous typical BAT mitochondria with
      or without multilocular lipid droplets. Immunocytochemistry confirmed that
      multilocular cells expressed mitochondrial UCP. Furthermore, the number of brown
      adipocytes and the density of mitochondrial cristae increased in parallel with
      exposure to cold. These results demonstrate that adipocytes expressing UCP are
      present in adipose deposits considered as white fat. They suggest the existence
      of a continuum in rodents between BAT and WAT, and a great plasticity between
      adipose tissue phenotypes. The physiological importance of brown adipocytes in
      WAT and the regulation of UCP expression remain open questions.

PMID- 1362573
TI  - Purification and characterization of recombinant pyrrolidone carboxyl peptidase
      of Bacillus subtilis.
AB  - Bacillus subtilis pyrrolidone carboxyl peptidase (Pcp) overexpressed in
      Escherichia coli was purified to homogeneity in less than 12 h using ammonium
      sulphate precipitation and hydrophobic interaction chromatography. The enzyme,
      which removes amino-terminal L-pyroglutamic acid from peptides, appears to be a
      tetramer of 25,200 molecular mass subunits. The protein cross-reacted with
      polyclonal antibodies raised against Pcp from Streptococcus pyogenes. The
      overexpressed enzyme exhibits an absolute substrate specificity towards N
      terminal pyroglutamyl residues with a Michaelis constant of 1.04 mM for L
      pyroglutamyl-beta-naphthylamide. The enzyme could be used for the removal of
      pyroglutamyl residues that block amino termini of proteins and peptides before
      performing Edman sequential degradation.

PMID- 1362574
TI  - Controlling ventricular dilation in the compromised myocardium.

PMID- 1362575
TI  - Considerations in pharmacotherapeutic treatment of movement disorders after
      traumatic brain injury.

PMID- 1362576
TI  - Proliferating cell nuclear antigen (PCNA) in common epidermal lesions. An
      immunohistochemical study of proliferating cell populations.
AB  - A commercially available antibody to proliferating cell nuclear antigen was used
      to characterize and compare proliferating cell populations in paraffin sections
      of benign, premalignant, and malignant lesions of human epidermis using routine
      immunohistochemical techniques. Three patterns emerged. An ordered pattern was
      found in prurigo nodularis and keratoacanthoma, wherein moderately and strongly
      positive nuclei were distributed in a continuous, basal-suprabasal layer of
      relatively uniform thickness. There was graded loss and ultimate extinction of
      PCNA staining in progressively more superficial epidermal cells. A basal
      dysplastic pattern was found in actinic keratosis and squamous cell carcinoma.
      Nuclei of essentially all dysplastic cells of both categories expressed PCNA,
      with a preponderance of strongly positive nuclei. These were localized to basal
      suprabasal zones that were often expanded. Loss of PCNA reactivity toward the
      surface was often abrupt. Bowen's disease exhibited a diffuse dysplastic pattern,
      wherein large numbers of moderately and strongly positive nuclei, in random
      array, were present in essentially full thickness distribution. In many fields,
      however, a layer of cytologically bland basal cells, with faint or no nuclear
      staining, was interposed between dysplastic epithelium and dermis. This study has
      demonstrated that proliferating cell populations in epidermal lesions can be
      assessed with simple, inexpensive methods. There were consistent differences
      between the proliferating cell populations of the various entities studied,
      differences that can be reasonably correlated with other known clinical,
      microscopic, and biologic features of the lesions. This technique should provide
      an interesting new avenue for study of diverse cutaneous diseases.

PMID- 1362577
TI  - No evidence for involvement of type 1 collagen structural genes in 'genetic
      predisposition' to alcoholic cirrhosis.
AB  - Type 1 collagen is the predominant collagen in cirrhotic livers. Each type 1
      collagen molecule contains three subunits, two are identical (the alpha 1 chains)
      and the sequence of the third (alpha 2) is very similar. They are encoded at the
      non-synthenic loci, COL1A1 and COL1A2 and restriction site dimorphisms have been
      described at each locus. Genetic factors have been invoked as a basis for
      increased susceptibility to alcoholic cirrhosis. One hypothesis is that
      genetically determined differences in type 1 collagen may be involved in this
      predisposition. We have examined this by analysing restriction fragment length
      polymorphisms at each type 1 collagen locus in leucocyte DNA from 56 unrelated
      patients with alcoholic cirrhosis and 74 local unrelated healthy controls. Based
      on the presence or absence of these restriction site dimorphisms four possible
      haplotypes were generated at COL1A1 and COL1A2. We found no significant
      difference in allele frequencies between alcoholic cirrhotics and controls and,
      unlike a previous small study, we found no particular haplotype of either gene
      was associated with alcoholic cirrhosis. Our study provides no evidence for
      involvement of type 1 collagen structural genes in a genetic predisposition to
      cirrhosis in alcoholics.

PMID- 1362578
TI  - Immunization with human thyrotrophin receptor peptide induces an increase in
      thyroid hormone in rabbits.
AB  - Eight rabbits were immunized with a synthetic peptide corresponding to the unique
      N-terminal region (termed N peptide; amino acid residues 29-57) in the
      extracellular domain of the human thyrotrophin (TSH) receptor. After 10 weeks,
      all of the eight rabbits produced anti-N peptide antibodies. Western blot
      analysis revealed that the antibodies recognized rabbit TSH receptor as an
      approximately 100 kDa protein. We compared the level of thyroid hormone in serum
      taken before immunization (preimmune sera) with that of serum taken after
      immunization (postimmune sera) in these immunized rabbits. Postimmune sera from
      the eight rabbits had higher mean (+/- S.D.) levels of tri-iodothyronine (T3) and
      thyroxine (T4) than did preimmune sera (T3, preimmune 0.82 +/- 0.26 micrograms/l
      vs postimmune 1.33 +/- 0.35, P < 0.01; T4, preimmune 33.7 +/- 10.0 micrograms/l
      vs postimmune 41.0 +/- 6.0, P < 0.05). T3 levels in four rabbits and T4 levels in
      four rabbits after immunization were over the normal range obtained from six age
      matched control rabbits. Seven rabbits exhibited thyroid-stimulating antibody
      (TSAb) activity with various degrees (241-545%). The concentration of T3 and T4
      did not increase over 10 weeks in either non-immunized rabbits (T3, preimmune
      0.89 +/- 0.34 micrograms/l vs postimmune 0.82 +/- 0.22; T4, preimmune 31.1 +/-
      7.3 micrograms/l vs postimmune 30.3 +/- 5.1) or other peptide-immunized rabbits
      (T3, preimmune 0.68 micrograms/l (n = 2) vs postimmune 0.69; T4, preimmune 33.1
      micrograms/l vs postimmune 26.4). These results indicate that experimentally
      produced anti-TSH receptor antibody with TSAb activity induces an increase in
      thyroid hormone in rabbits.

PMID- 1362579
TI  - N-methyl-D-aspartate (NMDA) and non-NMDA (metabotropic) type glutamate receptors
      modulate the membrane potential of the Schwann cell of the squid giant nerve
      fibre.
AB  - L-Glutamate application can produce three different responses in the membrane
      potential of the Schwann cell of the tropical squid, Sepioteuthis sepioidea,
      which appear to be mediated by three pharmacologically distinct classes of
      receptor. A class of non-NMDA-type receptors, with some similarities to
      metabotropic glutamate receptors, mediates the development of a rapid and long
      lasting hyperpolarization. Two pharmacologically distinct classes of NMDA-type
      receptor are present. One mediates the development of a slow depolarization
      accompanied by a long-lasting change in responsiveness of the Schwann cell. The
      second produces rapid depolarizing responses during the period of this changed
      responsiveness. All three types of receptor can be activated by dipeptides
      containing excitatory amino acids.

PMID- 1362580
TI  - The effect of a glutamate uptake inhibitor on axon-Schwann cell signalling in the
      squid giant nerve fibre.
AB  - The glutamate uptake blocker p-chloromercuriphenylsulphonic acid (PCMS) (100
      mumol l-1) does not block any of the membrane potential changes induced by the
      application of L-glutamate to the adaxonal Schwann cells of the giant axon of the
      tropical squid Sepioteuthis sepioidea. This indicates that these potential
      changes are not due to the activation of an electrogenic glutamate uptake system
      and supports the idea that they are due to the activation of specific glutamate
      receptors. The presence of PCMS (100 mumol l-1) reduces the activity of the
      glutamate uptake system sufficiently for the extracellular level of axonally
      released glutamate to exceed the threshold for the activation of the NMDA-type
      glutamate receptors in this preparation.

PMID- 1362581
TI  - Chemical modification studies of the active centre of Candida albicans chitinase
      and its inhibition by allosamidin.
AB  - Allosamidin, a glycoside antibiotic, is shown to be a strong, competitive
      inhibitor of semi-purified chitinase from yeast cells of Candida albicans. The
      inhibitory potency of allosamidin was pH-dependent, with IC50 values of 280 nM at
      pH 5.0 and 21 nM at pH 7.5. At higher, micromolar, concentrations, allosamidin
      inactivated this chitinase in a time- and concentration-dependent manner. Kinetic
      studies of this inactivation provided evidence for the formation of a reversible
      complex between allosamidin and chitinase, characterized by Kinact = 5 microM,
      followed by irreversible modification of the enzyme with velocity constant k2 =
      4.6 x 10(-3) s-1. Chemical modification studies with the use of group-specific
      reagents suggested the presence of Glu/Asp carboxyl group(s) at or near the
      active site, that were important for enzyme activity. The carboxyl-specific
      reagent, 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide, inactivated the chitinase
      in a single step process, with apparent second-order rate constant of 0.014 M-1 s
      1.

PMID- 1362582
TI  - Isolation and characterization of new fluoroacetate resistant/acetate non
      utilizing mutants of Neurospora crassa.
AB  - Sixty-two mutants of the filamentous fungus Neurospora crassa were isolated on
      the basis of resistance to the antimetabolite fluoroacetate. Of these, 14 were
      unable to use acetate as sole carbon source (acetate non-utilizers, acu) and were
      the subject of further genetic and biochemical analysis. These mutants fell into
      four complementation groups, three of which did not complement any known acu
      mutants. Mutants of complementation group 3 failed to complement acu-8,
      demonstrated similar phenotypic properties and proved to be closely linked (less
      than 2% recombination) but not allelic. Representatives of groups 2 and 4 were
      mapped to independent loci; the single representative of group 1 could not be
      mapped. The four complementation groups were therefore designated as genes acu-10
      to acu-13 respectively. All the mutants demonstrated normal acetate-induced
      expression of acetyl-CoA synthetase and the unique enzymes of the glyoxylate
      cycle and gluconeogenesis. The nature of these mutations is therefore quite
      different to those reported for other fungal species. Mutant acu-11 was unable to
      fix labelled acetate, indicating the loss of an initial transport function;
      partial enzyme lesions were observed for acu-12 (acetyl-CoA hydrolase) and acu-13
      (acetate-inducible NAD(+)-specific malate dehydrogenase).

PMID- 1362583
TI  - Distinct genetic groups of Giardia intestinalis distinguished by restriction
      fragment length polymorphisms.
AB  - The taxonomic status of the parasitic protozoal species Giardia intestinalis
      depends on the morphological similarity of all Giardia isolated from humans and
      the presumption that Giardia are host-specific. On the basis of electrophoretic
      data derived from examination of 26 enzyme loci in Australian isolates, it has
      been proposed that G. intestinalis is a species complex comprising three or four
      genetically distinct (but morphologically cryptic) species. These received the
      tentative designations of genetic groups I-IV (R. H. Andrews, M. Adams, P. F. L.
      Boreham, G. Mayrhofer & B. P. Meloni. International Journal for Parasitology 19,
      183-190, 1989). In the present study, two unrelated DNA probes (one specific for
      a gene encoding a trophozoite surface protein, the other detecting a non-coding
      repetitive sequence within the G. intestinalis genome) were used in Southern
      hybridization analyses to examine 10 axenic isolates of G. intestinalis,
      established from diverse geographical regions in Australia, together with the
      Portland-1 isolate from the USA. Both probes identified every isolate
      unambiguously as belonging to one or other of two genetic clusters.
      Electrophoretic analysis of the same samples indicated that these clusters
      correspond to the previously defined genetic groups I and II. No heterogeneity
      was apparent within the seven group I isolates using either probe. However, when
      probed with the repetitive sequence, the four isolates belonging to group II
      exhibited small differences in banding patterns, suggesting that this group may
      be less homogeneous than group I.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362585
TI  - Bacterial differentiation within Moraxella bovis colonies growing at the
      interface of the agar medium with the Petri dish.
AB  - Moraxella bovis was found to colonize the interface between agar and the
      polystyrene Petri dish, producing circular colonies when the inoculum was stabbed
      at a single point. The bacteria occurred in a thin layer of nearly uniform
      thickness, and colonial expansion occurred in at least two temporal phases. In
      the first phase, the radial colonial expansion was slow and non-linear. In the
      second phase, the radial expansion was linear. The interfacial colonies possessed
      three characteristic concentric growth zones. At the periphery was a narrow ring
      zone that enclosed another wider ring zone, which, in turn, surrounded a central
      circular zone. Different bacterial phase variants were recovered from these
      zones. The two outer ring zones yielded bacteria that formed agar surface
      colonies of spreading-corroding morphology, while cells from the innermost zone
      always yielded colonies with a different morphology. The uniform thickness of the
      colonies implied that replication was restricted to the outermost ring, and that
      the bacteria within the inner ring and inner circle had entered a quiescent
      state. The inner ring appeared to represent the lag in time needed for the
      replicative form to differentiate into the quiescent form. A different kind of
      variant was associated with wedge-shaped sectors within the colonies. The
      greatest number of these clonal variants appeared shortly after inoculation and
      their frequency decreased after the onset of linear growth. The period of slowest
      colonization coincided with highest frequency of clonal variant expression. It is
      proposed that the proliferative rate of the parental bacterial population exerted
      selective pressure on the expression of new clonal variants.

PMID- 1362584
TI  - Molecular analysis of isolates of Streptococcus suis capsular type 2 by
      restriction-endonuclease-digested DNA separated on SDS-PAGE and by hybridization
      with an rDNA probe.
AB  - This study was undertaken to assess the discriminatory value of restriction
      endonuclease (RE) digestion patterns of Streptococcus suis chromosomal DNA using
      polyacrylamide gel electrophoresis (SDS-PAGE) and DNA-rDNA hybridization. For the
      RE digestion patterns, DNAs were digested separately with the enzymes BamHI and
      BglII and the resultant fragments were separated by SDS-PAGE. An Escherichia coli
      rDNA probe derived from pKK3535 was used for the hybridization. Twenty-three S.
      suis capsular type 2 isolates recovered from diseased and clinically healthy
      pigs, from a human case, and from a cow were compared in this study. The majority
      of isolates associated with septicaemia belonged to one restriction endonuclease
      analysis (REA) profile group. Isolates associated with pneumonia belonged either
      to the REA profile group of isolates associated with septicaemia or to a second
      REA profile group. The REA profiles of isolates from clinically healthy animals
      were more heterogeneous. The REA profile of the type 2 reference strain, S735,
      which was originally isolated from a pig, was very different from those of the
      porcine and bovine isolates but similar to the profile of the human isolate. The
      profiles obtained after rDNA hybridization were more homogeneous. Although
      different patterns were detected in the 23 isolates, there was no correlation
      between the source of the isolate and the patterns observed with this technique.

PMID- 1362586
TI  - Effects of ischemia on regional ligand binding to adrenoceptors in the rat brain.
AB  - Changes in ligand binding to adrenoceptors ([3H]prazosin to alpha 1-receptors,
      [3H]idazoxan to alpha 2-receptors and [125I]cyanopindolol to beta-receptors)
      following transient cerebral ischemia were investigated using autoradiographic
      methods. The binding was quantified in brain sections from control rats, rats
      subjected to 15 min of 2-vessel occlusion ischemia, and rats with recirculation
      times of 1 h, 1 week or 4 weeks after ischemia. No significant change in alpha 1
      receptor binding was observed during and immediately following ischemia, but a
      decrease was noted in the vulnerable hippocampal CA1 region following 1 week's
      survival. In the parietal cortex, the ligand binding to alpha 1-receptors
      increased at 4 weeks. A reduced [3H]idazoxan binding was observed 1 h after
      ischemia in the temporal cortex and amygdala. No change in ligand binding to beta
      receptors was seen in the early phase postischemia, but a marked increase had
      occurred in the hippocampal CA1 region at 1 and 4 weeks after ischemia (+163% and
      +142%, respectively), presumably due to accumulation of macrophages expressing
      beta-receptors. The early postischemic changes in receptor binding may represent
      downregulation of the adrenoceptors by processes activated during ischemia, while
      neuronal degeneration, compensatory mechanisms in surviving neurons and
      proliferation of non-neuronal cells may account for the subsequent changes.

PMID- 1362587
TI  - Neurochemical abnormalities in Huntington's disease: neurotoxic mechanisms and
      neurotransmitter changes.

PMID- 1362589
TI  - Distinguishing acute and tardive akathisia by monitoring microvibration: a pilot
      study.
AB  - One acute and one tardive akathisia patients, respectively, and 10 neuroleptic
      treated schizophrenic patients were injected with biperiden 5 mg or saline and
      the response to anticholinergics was monitored by microvibration (MV) as an
      indicator of muscle tonus. These data were subjected to the Fast Fourier
      Transform and an averaged power spectrum was computed. The biperiden injection
      markedly reduced the power spectral values of MV in acute akathisia. In contrast
      with acute akathisia, the biperiden injection significantly increased the power
      spectral values of MV in tardive akathisia. The subjective feelings of akathisia
      patients were parallel to the power spectral values of MV. Control patients were
      not affected by such treatment. The present findings show that the subjective
      symptoms of akathisia can be well defined by the objective, differential response
      to anticholinergics in a manner similar to the visible extrapyramidal symptoms
      (dystonia, dyskinesia) induced by neuroleptics.

PMID- 1362588
TI  - The ambulatory care of HIV-infected persons: a survey of physician practice
      patterns.
AB  - OBJECTIVE: To describe the use of various counseling practices, examinations, and
      laboratory tests used by general internists in the primary care of HIV-infected
      persons. DESIGN: Mailed questionnaire survey. SUBJECTS: Random sampling of
      members of the Society of General Internal Medicine. RESULTS: Based on a 64%
      response rate (131/205), there are many areas of physician agreement in the
      ambulatory care of HIV-infected persons. Greatest physician consensus was seen in
      the use of viral serologic testing, vaccinations, and Pap tests. Most (70-80%)
      primary care physicians do not use surrogate markers such as beta 2-microglobulin
      and p24 antigen to follow disease progression; instead, they rely mostly on CD4
      lymphocyte counts. Sixty percent of physicians continue to order CD4 lymphocyte
      counts when a baseline count is under 200 cells/mm3. All studies are ordered more
      frequently for patients with more advanced disease. As a group, those physicians
      following the largest number of patients do not manage patients significantly
      differently from the less HIV-experienced physicians. CONCLUSIONS: Despite some
      variation, there is substantial consensus on the "routine" management of HIV
      infected persons. Clinical guidelines would be one mechanism for defining
      appropriate care of HIV-infected patients. The majority judgments of the
      practitioners studied here could be one component among various sources of
      information used by expert panels to define guidelines except where studies
      clearly indicate a different and more effective approach. Such incorporation
      might increase guideline acceptance by practicing clinicians.

PMID- 1362590
TI  - Quantitative EEG of elderly schizophrenic patients.
AB  - To investigate the brain function of elderly schizophrenic patients, quantitative
      EEGs of such patients were compared with those of healthy elderly controls. In
      schizophrenics, increases in delta and slow theta (4.0-6.0 Hz) waves were thought
      to be due to the influence of antipsychotics. Characteristic EEG features of
      these patients included the following: 1) more fast theta (6.0-8.0 Hz) wave was
      observed, with less alpha wave faster than 9.0 Hz, 2) the reduction in alpha 3
      (10.0-11.0 Hz) wave was limited to the frontal regions. The present EEG findings
      are thought to characterize the traits of the subtype of chronic severe
      schizophrenia. The reduction in alpha 3 wave in the frontal regions may be one
      expression of the hypofrontality of schizophrenia.

PMID- 1362591
TI  - Plasma ratios of tryptophan and tyrosine to other large neutral amino acids in
      manic-depressive patients.
AB  - The plasma ratio of each neutral amino acid (tryptophan (TRP), tyrosine (TYR),
      valine, isoleucine, leucine (LEU) or phenylalanine) to the sum of the other
      neutral amino acids was measured in 16 manic and 14 depressed patients. In the
      manics, there was a correlation between the psychomotor activity and the plasma
      TRP and LEU ratios. In the depressives, the depressed mood, retardation and
      global severity were correlated with the TRP ratio. The zotepine responders
      showed an increase in the TRP ratio after treatment. In the mianserin responders,
      the TYR ratio, which was high before the treatment, decreased to the normal range
      after the treatment. But, the plasma amino acid ratios remained unchanged in the
      patients treated with lithium carbonate or amitriptyline. These results suggest
      that, in manic-depressive illness, there might be abnormalities in the metabolism
      of neutral amino acids, mainly of TRP and TYR, and that the plasma TRP and TYR
      ratios might be important indicators for determining the efficacy of some drugs.

PMID- 1362592
TI  - Usefulness of antiparkinsonian drugs during neuroleptic treatment and the effect
      of clonazepam on akathisia and parkinsonism occurred after antiparkinsonian drug
      withdrawal: a double-blind study.
AB  - Antiparkinsonian drugs used for 117 chronic schizophrenic patients receiving long
      term neuroleptic treatment were withdrawn. Seventy-eight (66.7%) of the 117
      patients were without akathisia and/or parkinsonism at least for 6 weeks after
      the antiparkinsonian drug withdrawal. A double-blind study of clonazepam was
      carried out for 22 patients and clonazepam was effective on 8 patients (100%)
      with akathisia and on 3 patients (75%) with parkinsonism. The authors conclude
      that these data support the need for discontinuous use of antiparkinsonian
      medication during the long-term neuroleptic therapy of chronic schizophrenic
      patients and the effectiveness of clonazepam in managing antiparkinsonian drug
      withdrawal-induced akathisia and parkinsonism.

PMID- 1362593
TI  - [The 1st International Symposium of Mediterranean Countries on Arterial
      Hypertension "In the Future without Risk"].

PMID- 1362596
TI  - German Society for Pharmacology and Toxicology. Abstracts of the 4th winter
      meeting and of the 1st Microdialysis Symposium. Hannover, 2-5 December 1992.

PMID- 1362595
TI  - Demyelinating peripheral neuropathy in Creutzfeldt-Jakob disease.
AB  - We describe 2 patients of Jewish Libyan descent, who presented with a clinical
      syndrome compatible with Creutzfeldt-Jakob disease and who were found to have a
      mutation of codon 200 in the prion protein. The patients developed symptoms and
      signs of peripheral nerve involvement diagnosed by electrodiagnostic and
      histopathological studies as demyelinating neuropathy. This may be a rare
      manifestation of Creutzfeldt-Jakob disease.

PMID- 1362594
TI  - Adipose hormone-sensitive lipase preferentially releases polyunsaturated fatty
      acids from triglycerides.
AB  - Rat adipose hormone-sensitive lipase-mediated release of fatty acids from
      triglycerides was studied in three model systems: i) cultured preadipocytes
      containing polyunsaturated fatty acid-enriched triglyceride; ii) perfused
      epididymal fat pads; and iii) in vitro incubations of crude preparations of
      hormone-sensitive lipase with synthetic triglyceride-analogues as substrates. We
      found that cultured preadipocytes challenged with 10 microM norepinephrine tended
      to release more omega 6 and omega 3 polyunsaturated fatty acids than saturated
      fatty acids. Fat pads perfused with 10 microM norepinephrine preferentially
      released arachidonate and alpha-linolenate but tended to retain oleate and
      linoleate. Finally, crude preparations of hormone-sensitive lipase released from
      the triglyceride-analogue substrates alpha-linolenate twice as fast as oleate. We
      conclude that rat adipose hormone-sensitive lipase preferentially releases
      polyunsaturated fatty acids from triglycerides. We suggest that this may be a
      mechanism by which these fatty acids are kept from being trapped in fat depots
      and maintained in the circulation.

PMID- 1362598
TI  - Alpha 2-adrenergic receptors are involved in the suppression of luteinizing
      hormone release during acute fasting in the ovariectomized estradiol-primed rats.
AB  - It has been previously reported that the adrenergic system is involved in the
      control of feeding behavior and LH release. In the present study, the role of the
      adrenergic receptors in the suppression of LH release during acute fasting are
      examined by injecting the alpha 1-antagonist (prazosin), alpha 2-antagonists
      (idazoxan, SKF 86466-A, piperoxan), or beta-antagonist (propranolol) into the
      third ventricle of unfasted and 48 h fasted ovariectomized estradiol-treated
      rats. Blood samples were collected every 6 min for 3 h and the drugs were
      administered after the first hour of the sampling period. Prazosin caused a
      significant suppression of LH release in the unfasted animals while idazoxan and
      propranolol had no significant effects. In contrast, all alpha 2-antagonists
      blocked the inhibitory effect of fasting on LH release and significantly
      reinstated the suppressed LH release while prazosin and propranolol had no
      significant effects. We conclude from these results that the suppression of LH
      release during acute fasting is mediated by alpha 2-adrenergic receptors but not
      alpha 1- or beta-adrenergic receptors.

PMID- 1362597
TI  - Effect of thymosin alpha 1 on hypothalamic hormone release.
AB  - Thymosin alpha 1 (T alpha 1) is a well-characterized immunopotentiating
      polypeptide originally isolated from calf thymus. We have recently shown in vivo,
      probable hypothalamic effects of T alpha 1 to decrease the release of the
      pituitary hormones, TSH, PRL and ACTH from the pituitary gland. Therefore, in the
      present study we evaluated the effect of the peptide on the release of
      hypothalamic regulatory hormones: thyrotropin-releasing hormone (TRH) and
      corticotropin-releasing hormone (CRH), as well as somatostatin (SRIH), from
      medial basal hypothalamic (MBH) fragments incubated in vitro. After a preliminary
      time-course study indicated that a 30-min incubation period was optimal, it was
      used for all the other experiments. At the end of the incubation the tissue was
      still able to respond to a depolarizing K+ concentration for 15 min by a 4-fold
      increase of TRH concentration compared to control basal release during the
      preceding 30 min. T alpha 1 was shown to inhibit the release of TRH and CRH from
      MBH fragments incubated in vitro with a minimal effective dose (MED) of 10(-11)
      M. SRIH and CRH release was also inhibited but the MED for these peptides was 10(
      9) M. The relative responsiveness to the action of T alpha 1 was TRH greater than
      CRH, which was greater than SRIH. This correlated with our previous in vivo
      results for pituitary hormone release, except in the case of SRIH since we
      previously did not detect any significant effect of the peptide on growth hormone
      release. Finally, we evaluated the possible involvement of other
      neurotransmitters in the effect of T alpha 1 on TRH release.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1362599
TI  - Chronically administered nicotine attenuates bradykinin-induced plasma
      extravasation and aggravates arthritis-induced joint injury in the rat.
AB  - We recently showed that acute administration of nicotine in the rat decreases
      bradykinin-induced plasma extravasation and that adrenal medullary-derived
      epinephrine, acting at a beta 2-adrenergic receptor, mediates the nicotine
      effect. Since agents which decrease bradykinin-induced plasma extravasation have
      been associated with increased joint injury in a rat model of chronic
      inflammation (experimental arthritis induced by subcutaneous injection of
      Mycobacterium butyricum) we examined the effect of chronic nicotine on both
      plasma extravasation and the severity of joint injury. In normal rats, bradykinin
      induced plasma extravasation was decreased after nicotine administered both by
      repeated injection (10(-2) mg/kg, s.c., once per h for 4 h) and by continuous
      long-term infusion (subcutaneous mini-osmotic pump; 1.5 x 10(-3) mg/kg per h for
      30 days). Nicotine-induced inhibition of bradykinin-induced plasma extravasation
      did not show tachyphylaxis. In rats with arthritis, chronic administration of
      nicotine also produced a decrease in bradykinin-induced plasma extravasation.
      This effect of chronic nicotine in the arthritic rats was antagonized by co
      administration of hexamethonium (a nicotinic receptor antagonist), by surgical
      removal of the adrenal medulla, or by co-administration of ICI-118,551 (a beta 2
      adrenoceptor antagonist). Chronic administration of nicotine decreased the
      latency to the onset of arthritis and, in a dose-dependent manner, led to an
      increase in the radiographic joint injury score.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362600
TI  - The relation between transmitter release and Ca2+ entry at the mouse motor nerve
      terminal: role of stochastic factors causing heterogeneity.
AB  - The relation between quantal transmitter release and presynaptic Ca2+/Ba2+ entry
      at the mouse neuromuscular junction was studied, making use of the finding that
      in the presence of Ba2+ trains of nerve stimuli or brief nerve terminal
      depolarizations elicit "tails" of raised miniature end-plate potential frequency
      (fm) that reflect entry of Ba2+ per pulse, and hence effectiveness of pulses in
      opening Ca2+/Ba2+ channels; at the same time these pulses elicit end-plate
      potentials. With nerve stimulation in the presence of Ba2+ and Ca2+ and
      modulation of release by raised Mg2+ or bekanamycin, slopes of log quantal
      content (m) vs log apparent Ba2+ entry per pulse were close to 4, which is the
      same as the Hill coefficient for Ba2+ cooperativity derived from other data. With
      depolarizing pulses of varied intensity, however, similar plots gave slopes close
      to 2, with Ba2+ alone or in a mixture of Ca2+ and Ba2+. Thus, the relation
      between transmitter release and Ca2+ (or Ba2+) entry apparently depends upon how
      entry is varied; varying the numbers of channels opened is not the same as
      varying ion entry per channel. A mathematical model was developed to examine the
      consequences of heterogeneity of local Ca2+ (or Ba2+) between release sites,
      arising because of stochastic variation of number and time course of Ca2+
      channels opened per site; the experimental results were consistent with this
      model. It was therefore concluded that release is normally governed by
      intracellular Ca2+ close to points of Ca2+ entry through channels; stochastic
      factors give rise to more release than if Ca2+ were homogeneously distributed. If
      Ca2+ channels are uniformly close to release sites the average number of channels
      opened per site per action potential may be as low as 4.

PMID- 1362601
TI  - Dopaminergic and non-dopaminergic neurons in the ventral tegmental area of the
      rat project, respectively, to the cerebellar cortex and deep cerebellar nuclei.
AB  - It has been suggested recently that dopamine in the cerebellum not only acts as a
      precursor for noradrenaline in afferent fibers supplied by locus coeruleus
      neurons, but also subserves an independent transmitter role in a separate neural
      system. The present study was initiated to investigate the possible sources for
      dopaminergic innervation of the cerebellum. Employing anterograde and retrograde
      axonal tracing with cholera toxin and a combination of fluorescent retrograde
      axonal tracing with Fluoro-Gold and tyrosine hydroxylase immunofluorescence
      histochemistry, we found in the rat that the ventral tegmental area, containing
      the A10 dopaminergic cell group, sends projection fibers to the cerebellum
      bilaterally with a slight contralateral predominance. The projections from the
      ventral tegmental area to the cerebellum were segregated into the dopaminergic
      one to the cerebellar cortex and the non-dopaminergic one to the deep cerebellar
      nuclei. Dopaminergic fibers projecting from the ventral tegmental area to the
      cerebellar cortex terminated mainly in the granular layer, additionally in the
      Purkinje cell layer, but not at all in the molecular layer. They were distributed
      predominantly in the crus I ansiform lobule and paraflocculus, and to a lesser
      extent in the crus II ansiform lobule. On the other hand, non-dopaminergic fibers
      projecting from the ventral tegmental area to the deep cerebellar nuclei were
      seen to terminate mainly in the lateral nucleus, to a lesser extent in the
      interpositus nucleus, but not at all in the medial nucleus. The ventral tegmental
      area was also observed to receive projection fibers from the lateral and
      interpositus cerebellar nuclei bilaterally with a contralateral predominance. The
      projections from the ventral tegmental area to the cerebellum revealed in the
      present study might exert limbic influences upon the cerebro-cerebellar loops
      subserving the execution and co-ordination of voluntary movements.

PMID- 1362602
TI  - Molecular requirements for hapten binding to antibodies against glutamate and
      aspartate.
AB  - Molecular requirements for hapten recognition by antibodies raised in rabbits
      against glutaraldehyde conjugates of L-glutamate and L-aspartate were determined
      in enzyme immunoassays by measuring the displacement of binding of glutamate and
      aspartate, respectively, by a large number of selected haptens to two anti
      glutamate and two anti-aspartate sera. The results indicate that N-terminal
      modifications of the amino acids, such as the presence of an N-acetyl or N
      carbamyl group or the addition of a second amino acid to form dipeptides with C
      terminal glutamate or aspartate, are tolerated to variable degrees, more so by
      the aspartate than the glutamate antisera. The antibodies possess point-to-point
      recognition sites for the two carboxyl groups present in both amino acids. Strong
      shape complementarity between the amino acids and their respective binding sites
      is suggested by the lack of recognition of the appropriate D stereoisomers by any
      of the antibodies. Changes in the distance between the two carboxyl groups, or
      modification, replacement or loss of either or both carboxyl groups, strongly
      reduce or eliminate binding. Based on these results, we suggest that other
      antibodies raised to similar conjugates of these amino acids are likely to share
      similar recognition characteristics. In addition, the results provide a rational
      background for the evaluation of antibody specificity and the interpretation of
      results in immunocytochemical studies using antisera to glutamate and aspartate.

PMID- 1362604
TI  - A histaminergic H2-receptor antagonist, ranitidine, blocks the suppressive
      vasopressin response to fear-related emotional stress in the rat.
AB  - The effects of intracerebroventricularly (i.c.v.) administered histaminergic
      receptor antagonists on plasma levels of vasopressin, oxytocin, prolactin and
      adrenocorticotrophic hormone (ACTH) after fear-related emotional stress were
      investigated in the male rat. Pyrilamine, a histaminergic H1-receptor antagonist
      did not significantly alter the suppressive vasopressin or the facilitative
      prolactin response to nonassociatively applied emotional stress. On the other
      hand, i.c.v. administered ranitidine, a histaminergic H2-receptor antagonist,
      blocked these responses to stress. Pyrilamine again did not significantly change
      the suppressive vasopressin response to the associatively applied emotional
      stress. However, the drug attenuated the prolactin response slightly but
      significantly. Ranitidine blocked the suppressive vasopressin and the
      facilitative prolactin responses to the associatively applied emotional stress,
      but the drug did not change the facilitative oxytocin or ACTH response to the
      stress. Suppression of motor activity during the associatively applied emotional
      stress was not significantly changed by either of these antagonists. These
      results suggest that histaminergic H2 receptors are selectively involved in the
      neural pathways which mediate the suppressive vasopressin and the facilitative
      prolactin responses to fear-related emotional stress.

PMID- 1362605
TI  - 1st International Conference on Nutrition and Aging. Proceedings. Tokyo, Japan,
      October 28-30, 1991.

PMID- 1362603
TI  - Neuronal injury evoked by depolarizing agents in rat cortical cultures.
AB  - Chemical depolarization is often used to study neurotransmitter release. Three
      commonly used depolarizing agents, veratridine, potassium, and glutamate, were
      evaluated for neurotoxicity. Neuronal survival and lactate dehydrogenase efflux
      were measured to assay irreversible injury. In addition, video-enhanced
      differential interference contrast microscopy was used to measure acute neuronal
      swelling. We found that lactate dehydrogenase efflux and cell death associated
      with exposure to potassium and glutamate could be blocked by the competitive N
      methyl-D-aspartate antagonist amino-phosphonovaleric acid. Neuronal swelling was
      observed with all three agents, and could not be blocked by amino
      phosphonovaleric acid. These results suggest multiple mechanisms of neuronal
      injury accompanying chemical depolarization. A 60-min exposure to 100 microM
      veratridine increased lactate dehydrogenase appearing in the medium at the end of
      this exposure to 615% of control and produced a 62% loss of neurons after 20-24
      h. These effects could not be blocked by amino-phosphonovaleric acid at 500
      microM. Differential interference contrast imaging revealed acute neuronal
      swelling in response to veratridine within 5 min of exposure, and this swelling
      could not be blocked by amino-phosphonovaleric acid. A 60-min exposure to medium
      supplemented with 50 mM KCl caused a lactate dehydrogenase efflux of 204% of
      control and produced a 48% loss of neurons. Amino-phosphonovaleric acid blocked
      both the neuronal loss and the excess lactate dehydrogenase efflux. In addition,
      differential interference contrast monitoring showed no KCl-evoked swelling. In
      contrast, isotonic substitution of 50 mM KCl for NaCl resulted in acute swelling
      which could not be blocked by amino-phosphonovaleric acid, in addition to
      neuronal death and lactate dehydrogenase release. Glutamate was, as expected,
      neurotoxic, and as has been shown before, this toxicity could be blocked by amino
      phosphonovaleric acid. Observation of neurons exposed to 300 microM glutamate
      revealed that this treatment was invariably associated with neuronal swelling. In
      the presence of amino-phosphonovaleric acid, 81% of neurons swelled to greater
      than 110% by 30 min exposure to glutamate. These results suggest that
      experimental paradigms which investigate the effects of chemical depolarization
      upon central neurons are likely to be associated with reversible and irreversible
      forms of injury. This is of special importance to any study of the mechanisms of
      release of substances from central neurons.

PMID- 1362606
TI  - [VII National Congress of the FISME. Genova, 25-28 November 1992. Abstracts].

PMID- 1362610
TI  - Advances in Gene Technology: Feeding the World in the 21st Century. Proceedings
      of the 1992 Miami Bio/Technology Winter Symposium. Abstracts.

PMID- 1362608
TI  - Pre- and postsynaptic actions of nifedipine at an identified cholinergic central
      synapse of Aplysia.
AB  - The effects of the dihydropyridine (DHP) Ca2+ channel antagonist, nifedipine,
      were studied on the cholinergic synapse between the presynaptic neurones B4/B5
      and the postsynaptic neurones B3/B6 located in the buccal ganglion of Aplysia
      californica. Nifedipine (10 microM) decreased the presynaptic Ca2+ current by 30%
      40%. Blockade of DHP-sensitive Ca2+ channels, however, did not affect quantal
      transmitter release from the presynaptic neurones. Thus, at this synapse, DHP
      sensitive Ca2+ channels appear not to be involved in acetylcholine (ACh) release.
      The postsynaptic response to an ionophoretic application of ACh was decreased by
      nifedipine, pointing to a blocking action of the drug on the postsynaptic
      receptor/channel complex. Nifedipine was also found to activate protein kinase C,
      which in turn induces an increase in the nifedipine-resistant presynaptic Ca2+
      influx and in the number of released ACh quanta. These effects of nifedipine
      could be prevented by a previous application of 1,5-(isoquinolinylsulfonyl)-2
      methyl-piperazine (H-7), a protein kinase blocker.

PMID- 1362607
TI  - Contribution of Ca2+ inflow to quantal, phasic transmitter release from nerve
      terminals of frog muscle.
AB  - Evoked quantal release from sections of frog endplates contained in an
      extracellular electrode has been investigated with Ca2+ inflow prevented by
      superfusing the extracellular space with a Ringer's solution containing Cd2+e or
      with an "intracellular", EGTA-buffered solution containing less than 0.1 microM
      Ca2+e. Pulse application and recording were by a perfused macro-patch-clamp
      electrode. The muscle outside the electrode (bath) was superfused with Ringer's
      solutions containing Cd2+b to block Ca2+ inflow and normal (1.8 mM) or elevated
      (10 mM) Ca2+b. The depolarization level of the terminal during current pulses
      that generated maximal Ca2+ inflow was used as unit relative depolarization.
      Starting from a threshold above 0.5 relative depolarization, the average release
      increased by a factor of about 1000 with increasing depolarization, reaching a
      plateau above 1.2 relative depolarization. The high level of plateau release
      extended to at least a relative depolarization of 4, i.e. to about +200 mV. When
      Ca2+ inflow was prevented in the section of the terminal within the electrode,
      release was depressed strongly for relative depolarizations around 1, i.e. at
      potentials at which Ca2+ inflow is high. However, for large depolarizations (>
      1.5 relative units), the depression of release by block of Ca2+ inflow was weak
      or absent. The time course of release, measured in distributions of the delays of
      quanta after the depolarizing pulse, was unaffected by block of Ca2+ inflow. If
      the extra-electrode superfusion of Ca2+b of the muscle was elevated to 10 mM and
      Cd2+b was 0.1 mM or 0.5 mM, perfusion of the electrode with solutions below 0.1
      microM Ca2+e raised the average release paradoxically. With 0.5 mM Cd2+b this
      paradoxical increase of release was, on average, 4-fold at 6 degrees C, and 19
      fold at 16 degrees C. Quantal endplate currents recorded in less than 0.1 microM
      Ca2+e had slightly increased amplitudes, and decay time constants were prolonged
      by about 50%. The results are interpreted to support the Ca2+/voltage theory of
      release, which proposes that evoked, phasic release is controlled by both
      intracellular Ca2+ concentration and another membrane-depolarization-related
      factor. If the resting intracellular Ca2+ concentration is sufficiently high,
      large depolarizations can elicit release independent of the presence or absence
      of Ca2+ inflow.

PMID- 1362609
TI  - Inwardly rectifying potassium conductances in AtT-20 clonal pituitary cells.
AB  - We have detected two inwardly rectifying potassium conductances in AtT-20 clonal
      corticotrophs, a cell line derived from the mouse pituitary gland. An agonist
      independent potassium conductance was activated by voltage steps negative to the
      reversal potential for potassium (VK) and was completely blocked by 1 mM barium
      in the bathing solution. The conductance was transient and inactivated completely
      with a time constant of about 80 ms. Reducing the external sodium concentration
      from 140 mM to 14 mM attenuated inactivation. In the presence of 100 nM
      somatostatin an inwardly rectifying conductance, which reversed at potentials
      close to VK, was also elicited. This conductance exhibited a maximal slope
      conductance that increased with increasing extracellular potassium. Rectification
      depends on both voltage and extracellular potassium concentration (Vm-VK). The
      inward current induced by somatostatin during voltage steps negative to VK was
      completely blocked by 1 mM extracellular barium, whereas the outward somatostatin
      induced current activated at the holding current, which was about 30 mV positive
      to VK, was unaffected by 1 mM extracellular barium. The muscarinic agonist
      carbachol (10 microM) also induces an inwardly rectifying conductance of similar
      magnitude to that induced by somatostatin. Since the agonist-independent
      potassium current exhibits sodium-dependent inactivation, whereas the hormone
      induced current does not inactivate, these currents are probably carried by
      different populations of potassium channels.

PMID- 1362611
TI  - [Pentasomy X: a clinical case report].
AB  - Cytogenetic investigations gave evidence of pentasomy X in a 3-year-old female
      with typical facies and psychomotor retardation. The parents and the grandparents
      showed a normal karyotype. The clinical symptoms of our case were compared with
      the other authors, we found a low birth weight, short stature, delayed expressive
      language, multiple abnormalities of craniofacial skeleton and some minor
      deformities of the arts. The parental origin of the extra set of X chromosome
      were determined by the restriction fragment length analysis (RFLPs) using the
      very polymorphic probes M27beta, L1.28 and St14. These data support the
      hypothesis of a maternal meiotic double non-disjunction.

PMID- 1362612
TI  - [Cooperative study of systolic arterial hypertension in the elderly patient
      (SHEP). Comments].
AB  - SHEP (Systolic Hypertension in the Elderly Program) is a multicenter controlled
      therapeutic trial which included 4,736 subjects aged 60 years and over, who had
      isolated systolic hypertension at three consecutive visits at the outpatient
      clinic. The treatment, based on low doses of diuretic (chlorthalidone 12.5-25 mg
      daily) combined, when necessary, with a cardioselective beta-blocker (atenolol 25
      to 50 mg daily), significantly reduced the incidence of cerebrovascular and
      coronary events; the relative risk reduction for total mortality was not
      statistically significant. The beneficial cardiovascular effects were observed in
      both sexes, and in the 80+ age group. These results show that this particular
      therapy applied to this form of hypertension decreases the risk of both coronary
      and cerebral events, as was already suggested by the meta-analysis of the
      controlled therapeutic trials performed with diuretics, beta-blockers and other
      older antihypertensive drugs in patients with permanent diastolic hypertension.
      They also show the limitations of this therapeutic strategy, which controlled
      only 50 percent of the patients who were, however, highly selected, especially
      concerning the absence of associated morbid conditions and treatments. The need
      for, and feasibility of, new controlled therapeutic trials comparing the
      mortality and morbidity associated with various new antihypertensive therapies
      must now be discussed.

PMID- 1362614
TI  - The effect of pertussis toxin treatment on alpha-1-adrenoceptor-mediated pressor
      responses in the pithed rat: dependence on agonist efficacy but not chemical
      class.
AB  - The role of pertussis-toxin-sensitive guanine nucleotide regulatory proteins (G
      proteins) in the signal transduction processes involved in post-junctional
      vascular alpha 1-adrenoceptor-mediated vasoconstriction has been investigated in
      the pithed rat using two chemical classes of alpha-adrenoceptor agonists, the
      phenethylamines and imidazolines, in order to determine if they utilize different
      signal transduction mechanisms. Pertussis toxin pretreatment (50 micrograms/kg,
      i.v., 3 days prior to experimentation) slightly inhibited the pressor response to
      the full alpha 1-adrenoceptor agonist of the phenethylamine class (-)
      norepinephrine (in the presence of rauwolscine, 1 mg/kg, i.v.), whereas it
      markedly inhibited the pressor response to the partial alpha 1-adrenoceptor
      agonist of the imidazoline class oxymetazoline (in the presence of rauwolscine, 1
      mg/kg, i.v.). However, after elimination of the alpha 1-adrenoceptor reserve for
      (-)-norepinephrine with phenoxybenzamine (0.1 mg/kg, i.v.), the pressor response
      to this agonist became sensitive to inhibition by pertussis toxin treatment. The
      pattern of inhibition of alpha 1-adrenoceptor-mediated pressor responses produced
      by pertussis toxin was similar to that produced by the calcium channel antagonist
      nifedipine (1 mg/kg, i.a.). The results support the hypothesis that vascular
      alpha 1-adrenoceptors may be coupled to a G protein which is sensitive to
      pertussis toxin and which couples the alpha 1-adrenoceptor to the influx of
      extracellular calcium, which possibly another G protein that is insensitive to
      pertussis toxin that couples the alpha 1-adrenoceptor to the release of
      intracellular calcium. The intrinsic efficacy of the agonist, and not its
      chemical class, determines which signal transduction mechanisms will be utilized.

PMID- 1362613
TI  - Role of sulphydryl-containing agents in the management of recurrent attacks of
      ulcerative colitis. A new approach.
AB  - This double-blind randomised study investigated the role of sulphydryl-containing
      agents in the management of recurrent attacks of ulcerative colitis. To this end,
      DL-cysteine (200 mg 4 times daily) and DL-methionine-methyl sulphonium chloride
      (MMSC, 500 mg 4 times daily) were administered orally. Patients with recurrent
      attacks of moderate proctosigmoidal ulcerative colitis, despite prophylaxis by
      oral sulphasalazine (2 g daily), were given prednisolone by mouth, 10 mg four
      times a day, sulphasalazine by mouth, 500 mg four times a day, and morning and
      evening retention enema (Predsol 20 mg) alone or with cysteine or MMSC. After 2
      weeks of treatment with sulphasalazine and prednisolone, 51% of patients (n = 45)
      were symptom free. Addition of cysteine (n = 46) or MMSC (n = 47) to this regimen
      controlled the symptoms within 2 weeks in 85% of patients (p < 0.01). During 12
      months of prophylactic treatment, 5% of patients (n = 42) receiving
      sulphasalazine (2 g daily) and cysteine and 5% of patients (n = 41) taking
      sulphasalazine (2 g daily) and MMSC relapsed, relative to 27% of cases with
      sulphasalazine (2 g daily) alone (p < 0.01). These results demonstrate that
      sulphydryl-containing agents play a key role in the treatment of and protection
      against ulcerative colitis.

PMID- 1362615
TI  - An evaluation of structural and functional prefrontal deficits in schizophrenia:
      MRI and neuropsychological measures.
AB  - Magnetic resonance imaging was used to assess prefrontal brain structure in 17
      schizophrenic, 18 psychiatric control, and 19 normal control subjects of
      comparable age, social background, and educational status, while three
      neuropsychological measures were used to assess prefrontal functioning.
      Schizophrenic patients had significantly smaller prefrontal areas than both
      psychiatric control and normal control subjects in all three planes. When
      posterior brain area and temporal lobe were entered into statistical analysis as
      covariates, they did not explain the prefrontal deficits. Schizophrenic patients
      made more perseveration errors on the Wisconsin Card Sorting Task and had fewer
      correct responses on the Spatial Delayed Response Task than normal control
      subjects. Schizophrenic patients performed more poorly than psychiatric control
      subjects on the Block Design Test. No group differences were found on three other
      nonfrontal tasks. These data lend some support to the role of prefrontal deficits
      in the development of schizophrenia.

PMID- 1362616
TI  - Fluoxetine and trifluoperazine in human brain: a 19F-nuclear magnetic resonance
      spectroscopy study.
AB  - Fluorine-19 (19F) is a nonradioactive isotope that is well-suited to nuclear
      magnetic resonance spectroscopy (NMRS) and is a constituent of several
      medications used to treat psychiatric illnesses. Fluoxetine, a trifluorinated
      agent, generated a signal from brain that was readily measured by 19F-NMRS.
      Estimated brain concentrations ranged from 1.3-5.7 micrograms/ml in six subjects
      at a steady state dose of 40 mg/day. Enhanced sensitivity of 19F has been
      obtained by conforming the surface coil to the shape of the forehead. Hence, at
      the current state of development, 19F-NMRS can be applied to clinical questions
      relevant to concentrations of fluoxetine in brain. We also report observation of
      NMRS signals from fluorinated neuroleptics in a number of patients at steady
      state. These signals continue to be difficult to obtain, although a correlation
      between dose and estimated brain concentrations is suggested.

PMID- 1362617
TI  - Operational criteria for senile dementia of Lewy body type (SDLT).
AB  - Recent reports have suggested that brain stem and cortical Lewy body formation
      may identify a neurodegenerative disorder in elderly demented individuals which
      accounts for up to 20% of cases of senile dementia coming to autopsy.
      Retrospective analysis of case notes of 21 autopsy patients with
      neuropathologically proven senile dementia of Lewy body type (SDLT) and 37 cases
      with neuropathologically proven Alzheimer's disease (AD) identified a
      characteristic clinical syndrome in SDLT. Fluctuating cognitive impairment;
      psychotic features including visual and auditory hallucinations, and paranoid
      delusions; depressive symptoms; falling and unexplained losses of consciousness
      were all seen significantly more often than in AD. Over half of the SDLT patients
      in this series who were given neuroleptics in standard dose showed acute and
      often irreversible adverse reactions indicative of a neuroleptic sensitivity
      syndrome. The survival time of drug treated patients was reduced by 50%.
      Operational criteria to aid in the clinical distinction between SDLT and AD
      patients are proposed and hypotheses regarding possible aetiology and treatment
      discussed.

PMID- 1362618
TI  - Posed facial expressions of emotion in schizophrenia and depression.
AB  - The goals of the present study were to explore: (1) whether schizophrenics,
      depressives, and normals differ in their likelihood of expressing different
      emotions; and (2) whether the types of expressions subjects exhibit are
      associated with their level of reported depressive symptomatology. Subjects were
      asked to imagine: seeing, smelling, or tasting something disgusting; and having
      something wonderful happen to them. Subjects were asked to show the experimenter
      what their face would look like if these things happened. The groups differed in
      how frequently they exhibited anger or contempt in the first condition and
      happiness in the second condition. The depressives were most likely to exhibit
      anger/contempt and least likely to exhibit happiness. Using Beck Depression
      Inventory scores as dependent variables, there were significant interactions
      between diagnostic group and the type of facial expressions exhibited. The
      associations between facial expressions and BDI scores were in the opposite
      directions for depressives and schizophrenics.

PMID- 1362619
TI  - Psychotropic and medical drug interactions.
AB  - In a number of situations, drugs used to treat psychiatric and physical illnesses
      are coadministered to patients suffering primarily from a psychiatric illness.
      Hence, coadministration of medical and psychiatric drugs is not uncommon. With
      increasing use of multiple drugs, our ability to treat a number of disorders has
      increased, but simultaneously, the problem of drug interactions has also assumed
      importance. A number of factors contribute to such drug interactions in
      psychiatric patients. All these interactions are both pharmacologically and
      genetically determined. Genetic susceptibility is not practical to determine. It
      is therefore essential for the physician to employ drug combinations only when
      necessary, be aware of the known clinically significant interactions, anticipate
      and watch for them, avoid dangerous combinations, and monitor the patients
      receiving combination of drugs with vigilance.

PMID- 1362621
TI  - Short-Course Therapy: Improved Patient Compliance and Therapeutic Benefit.
      Proceedings of a symposium at the 5th European Congress of Clinical Microbiology
      and Infectious Diseases. Oslo, Norway, 9-11 September 1991.

PMID- 1362620
TI  - Release of neutrophil proteinase 4(3) and leukocyte elastase during phagocytosis
      and their interaction with proteinase inhibitors.
AB  - Neutrophil proteinase 4 (NP4) is a major neutral proteinase of the human
      polymorphonuclear (PMN) leukocyte, which is present in amounts similar to
      leukocyte elastase. NP4(3) is a potent, non-specific proteinase, which may
      degrade structural and soluble proteins in the tissues and body fluids, and it
      has been implicated as an important pathogenetic factor in lung emphysema. We
      have studied the release of elastase and NP4(3) in an in vitro model of
      phagocytosis. alpha 1-proteinase inhibitor (alpha 1-PI) is the major plasma
      inhibitor of both leukocyte elastase and NP4(3), but alpha 1-PI bound leukocyte
      elastase more readily than NP4(3). The basic conditions were designed so that
      some proteolytic activity was present in the medium. Addition of increasing
      amounts of Secretory leukocyte protease inhibitor (SLPI) to the incubation
      mixtures resulted in binding of leukocyte elastase to this inhibitor and
      extinction of free proteolytic activity against both natural and synthetic
      substrates. The progressive binding of leukocyte elastase to SLPI instead of
      alpha 1-PI was paralleled by an increasing binding of NP4(3) to alpha 1-PI. SLPI
      is a potent inhibitor of leukocyte elastase and cathepsin G, and although it
      lacks inhibitory effect on NP4(3), it may obviously indirectly aid in the binding
      and inhibition of NP4(3) to alpha 1-PI, by taking care of at least part of the
      leukocyte elastase. As a specific NP4(3)-inhibitor is not readily available for
      therapeutic use, this effect may prove useful under in vivo conditions and
      enhance the protective effect of administered recombinant human SLPI.

PMID- 1362623
TI  - Dynamic Dynamometry in Research and Clinical Work. Symposium. Stockholm, Sweden,
      October 25, 1991. Abstracts.

PMID- 1362622
TI  - Brain Injury Rehabilitation, Assessment and Evaluation. Proceedings of a
      symposium. Goteborg, Sweden, September 18-20, 1991.

PMID- 1362624
TI  - Novel Approaches to the Use of Etoposide. Proceedings of a workshop. December 5
      7, 1991.

PMID- 1362625
TI  - Filariasis surveillance at the post-control stage in China.
AB  - From 1956, when filariasis control was first listed in our national program, up
      to 1991, a cumulative total of 677,931,521 person-time blood examinations and
      217,472,045 person-time diethylcarbamazine treatments were made in the whole
      country, and 835 (96.6%) out of the 864 endemic counties achieved the criterion
      for control of filariasis. Surveillance data collected in various provinces,
      autonomous regions and municipalities starting from the second year after they
      reached the criterion for control of filariasis demonstrated that in 1991 the
      microfilarial rate in human populations and natural infection of filarial larvae
      in mosquito vector populations in previous endemic areas had already declined to
      a very low level, even zero, without resurgence in quite a number of villages. In
      some places where filariasis was brought under control relatively early, the anti
      filarial antibody positive rate of the human population has fallen to a level the
      same as or similar to that in nonendemic areas. Therefore, the data suggest that
      in most places where filariasis has been controlled, the transmission of
      bancroftian filariasis and periodic malayan filariasis has been interrupted.
      However, filariasis is still endemic in 29 counties in China at present, the
      danger of introduction of sources of infection by the floating population hasn't
      been extinguished yet, and there are still a few areas with weak links in
      filariasis control. Therefore, control work still needs to be strengthened and
      systematic surveillance must be pursued until the elimination of filariasis in
      the whole country.

PMID- 1362626
TI  - Cannibalism and carnivory in Toxorhynchites splendens (Diptera: Culicidae).
AB  - Laboratory reared larvae of Toxorhynchites splendens, which were previously
      starved for 24 hours, cannibalized eggs of their own kind or preyed upon the eggs
      of other species (Aedes aegypti and Anopheles stephensi) present on the surface
      of water in small containers. Second and third instars consumed eggs faster than
      first and fourth instars. The first instar consumed larvae of its own kind faster
      than the other instars, in the absence of other prey. However, when prey larvae
      were provided, there was a significant fall in the rate of cannibalism.

PMID- 1362627
TI  - Cannibalistic behavior in Armigeres subalbatus (Diptera: Culicidae).
AB  - Phenomenon of natural cannibalism was observed to be exhibited by late (III and
      IV) instar larvae of Armigeres subalbatus. Cannibalistic behavior in this species
      was studied in response to food and density. Cannibalism among late instars was
      found to occur even in the presence of an adequate quantity of food. The rate of
      cannibalism was enhanced when food was restricted to only the early stages. Even
      in the total absence of food early instars did not show any cannibalistic
      behavior. Density had no influence on the rate of cannibalism. Under forced
      cannibalism and predation fourth instar larvae could not successfully pupate but
      the duration was prolonged. Cannibalism was thus facultative without any value
      for the survival of larvae. It may help in maintaining a balance in immature
      density in their natural habitats.

PMID- 1362628
TI  - Biting activity of mosquitos (Diptera: Culicidae) at a malarious site in Palawan,
      Republic of The Philippines.
AB  - Fifty-one species of mosquitos were collected at a malarious site in western
      Palawan, Philippines. Anopheles flavirostris, which is the primary malaria
      vector, was mildly exophagic and zoophilic, and had a peak biting activity from
      0030-0130 hours. An. balabacensis, a secondary vector, was endophagic,
      anthropophilic, and was primarily active between 2000-0030. Of the 3 main genera,
      Culex were the most zoophilic, Aedes were the most anthropophilic, and Anopheles
      had species in both extremes. An. annularis, Ae. vexans, and Cx. vishnui showed
      similar biting activity patterns during both the rainy or dry seasons.

PMID- 1362629
TI  - Larval habitat of Armigeres subalbatus (COQ) and its characteristics in
      Pondicherry.
AB  - Larval habitats of Armigeres subalbatus were delineated in urban and rural areas
      of Pondicherry. Survey of various potential mosquito breeding habitats revealed
      that septic tanks were the typical breeding habitat in both areas and the
      proportion was significantly higher in urban areas. The productive status of
      septic tanks differed in different months and the overall proportion breeding Ar.
      subalbatus was significantly higher in urban areas (0.0447) compared to rural
      areas (0.0181). Sporadic breeding observed in receptacles holding water admixed
      with cow-dung, was however insignificant. Among the various physico-chemical
      factors of septic tank habitat analysed in relation to breeding, only ammonia
      nitrogen was found to be significantly correlated with immature density.

PMID- 1362630
TI  - Effect of chronic substance abuse on the neuropsychological performance of
      intravenous drug users with a high prevalence of HIV-1 seropositivity.
AB  - Limited data are available on cognitive performance in populations of intravenous
      drug users during the early, asymptomatic stages of human immunodeficiency virus
      type 1 (HIV-1) infection. Between 1988 and 1990, 151 participants from the AIDS
      Link to Intravenous Experience (ALIVE) Study in Baltimore, Maryland, were
      evaluated neuropsychologically on a semiannual basis. This analysis focused on
      whether history of substance abuse influenced neuropsychological test
      performance. At baseline, 102 participants were HIV-1-seropositives who were free
      of acquired immunodeficiency syndrome and 49 participants were seronegative.
      Multivariate analyses, adjusting for correlation of repeated outcome measures,
      were conducted to determine predictors of neuropsychological functioning. Effects
      of the frequency of reported past use of marijuana, heroin, cocaine,
      barbiturates, and alcohol were not statistically associated with performance on
      the tests. Age and education were the most important predictors of test
      performance, and a significant practice effect was observed for most measures.
      After adjustment for age, education, the practice effect, and frequency of drug
      use, neuropsychological performance over time did not vary by HIV-1 serostatus.
      Overall, after acutely intoxicated individuals were excluded, neither frequency
      of drug and alcohol use nor HIV-1 seropositivity significantly influenced
      neuropsychological test performance over a 1-year period.

PMID- 1362631
TI  - C syndrome and omphalocele: another example.

PMID- 1362632
TI  - A rapid colorimetric assay for gamma-glutamyl hydrolase (conjugase).
AB  - A simple procedure for the measurement of gamma-glutamyl hydrolase (conjugase)
      activity is described. Glutamic acid released from pteroylpenta-gamma-glutamate
      by hog kidney and chicken pancreas conjugases was quantitated using the dye 4,4'
      bis(dimethylamino)benzophenone hydrazone. The procedure involves hydrolysis of
      the folylpoly-gamma-glutamate substrate by conjugase, conversion of glutamate to
      alpha-ketoglutarate by L-glutamate dehydrogenase and colorimetric measurement of
      the BDBH derivative of alpha-ketoglutarate. The release of as little as one nmol
      of glutamic acid from the substrate can be measured by this procedure, which is
      well suited for the assay of a variety of conjugase preparations. In addition,
      the method should provide a general assay for the enzymatic hydrolysis of various
      folate and antifolate polyglutamates.

PMID- 1362633
TI  - High-resolution two-dimensional electrophoresis of nuclear proteins: a comparison
      of HeLa nuclei prepared by three different methods.
AB  - A comparative analysis of HeLa cell nuclear proteins is presented using Iso-Dalt
      methods of protein resolution in two dimensions. The nuclear proteins were
      prepared by (1) spin through glycerol cushion, (2) spin through sucrose cushion,
      or (3) Triton wash. Improved resolution of total nuclear proteins in the range of
      pH 4.5-6.0 was achieved by substituting longer isotubes in combination with broad
      range ampholines during the isoelectric focusing step. An attempt to indicate
      silver stainable protein spots common to total cellular extracts and nuclear
      preparations has been made. Also, proteins that appear to be well represented in
      all three nuclear preparations and remain undetectable in the total cellular
      protein pattern have been marked as probably being enriched nuclear proteins.
      Such a comparative analysis of whole nuclear protein preparations made it
      possible to document that the different preparations preserved the same set of
      proteins. The Triton-wash method of obtaining nuclei was identified as the
      preferred choice. Coomassie-stained gels and blots of these nuclear proteins
      could serve as a guide for accessing relevant protein spots for further
      biochemical analysis such as immunoblotting.

PMID- 1362634
TI  - Incidence and natural history of Mycobacterium avium-complex infections in
      patients with advanced human immunodeficiency virus disease treated with
      zidovudine. The Zidovudine Epidemiology Study Group.
AB  - To determine the incidence and natural history of Mycobacterium avium-complex
      infections in persons with advanced human immunodeficiency virus (HIV) infection,
      we studied a multicenter cohort of 1,020 persons with acquired immunodeficiency
      syndrome (AIDS) or the AIDS-related complex (ARC) and CD4 cell count < 0.250 x
      10(9)/L initially treated with zidovudine between April 1987 and April 1988. M.
      avium-complex infections developed in 123 (12%) patients during follow-up, with a
      2-yr actuarial risk of 19%. Patients with an initial diagnosis of Pneumocystis
      carinii pneumonia were more likely to develop M. avium-complex infections than
      patients with an initial diagnosis of another opportunistic disease or of ARC (p
      = 0.002). Individuals developing M. avium-complex infections had lower baseline
      CD4 cell counts, hematocrits, lymphocyte counts, and total white blood cell
      counts than those who did not develop M. avium-complex infection. During follow
      up, individuals who developed M. avium-complex infections were more likely to
      have severe anemia, to experience zidovudine dose reductions, and to die than
      were patients without M. avium-complex (p < 0.001). By proportional hazards
      analysis, a baseline CD4 cell count < 0.100 x 10(9)/L, development of severe
      anemia, P. carinii pneumonia during follow-up, and zidovudine dose interruption
      were significantly associated with subsequently developing M. avium-complex
      infection. A proportional hazards analysis of survival showed that M. avium
      complex infection, severe anemia, zidovudine dose interruption, occurrence of an
      opportunistic infection, CD4 cell count < 0.100 x 10(9)/L, baseline AIDS
      diagnosis, and transfusion independently predicted an increased risk of
      death.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362636
TI  - Myopathy in severe asthma.
AB  - Myopathy complicating the therapy of severe asthma has been recently described in
      several case reports. Twenty-five consecutive patients admitted to the intensive
      care unit (ICU) at this hospital for mechanical ventilation for severe asthma
      were studied for the incidence of creatine kinase (CK) enzyme rise and for the
      development of clinical myopathy. Pharmacologic therapy was standardized, every
      patient receiving corticosteroids and aminophylline intravenously and salbutamol
      both nebulized and intravenously. Twenty-two patients received muscle relaxant
      therapy with vecuronium. In 19 of 25 (76%) of patients there was elevation of CK
      levels to a median of 1,575 U/L (range, 66 to 7,430) occurring 3.6 +/- 1.5 days
      after admission. In nine patients there was clinically detectable myopathy. The
      presence of either myopathy or CK enzyme rise was associated with a significant
      prolongation of ventilation time. Arterial blood gas measurements on admission to
      the ICU revealed a pH (mean +/- SD) of 7.07 +/- 0.21, a PaCO2 of 87.2 +/- 32.7,
      and a PaO2 (with a high FIO2) of 129 +/- 97 mm Hg; however, no correlation was
      found between the severity of initial metabolic disturbance and the subsequent
      development of myopathy. There was no association between the type of
      corticosteroid administered and the subsequent development of myopathy. Patients
      with myopathy had received a significantly higher total dose of vecuronium when
      compared with those who did not develop myopathy (p < 0.001, Kruskal Wallis
      test). We have therefore found a surprisingly high incidence of CK enzyme rise
      and myopathy in this group of mechanically ventilated patients with severe
      asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362635
TI  - CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil
      infiltration into the mouse trachea.
AB  - In order to determine the role of CD4+ and CD8+ T-cells and of interleukin-5 (IL
      5) in causing antigen-induced eosinophil infiltration into the site of airway
      late-phase reaction, we examined the effect of the in vivo depletion of CD4+ and
      CD8+ T-cells on the eosinophil infiltration of the trachea induced by antigen
      inhalation in mice. We also studied the effect of anti-murine IL-5 monoclonal
      antibody (mAb) on the antigen-induced eosinophil infiltration in the trachea. The
      eosinophil infiltration into the trachea of ovalbumin (OVA)-sensitized BALB/c
      mice began to increase 9 h after OVA inhalation and persisted for more than 48 h.
      The in vivo depletion of CD4+ T-cells by pretreatment with anti-L3T4 mAb
      significantly decreased the eosinophil infiltration induced by OVA inhalation in
      the trachea of sensitized mice. However, the in vivo depletion of CD8+ T-cells by
      pretreatment with anti-Lyt-2 mAb had no significant effect on OVA-induced
      eosinophil infiltration in the trachea. Pretreatment with anti-murine IL-5 mAb
      also decreased OVA-induced eosinophil infiltration in the trachea. In contrast,
      neither disodium cromoglycate nor a selective antagonist for platelet-activating
      factor CV-6209 decreased OVA-induced airway eosinophilia in the mouse. Our
      results provide direct evidence that CD4+ but not CD8+ T-cells mediate antigen
      induced eosinophil recruitment in the airways and that IL-5 mediates this
      eosinophil recruitment.

PMID- 1362638
TI  - Sinusitis-induced subdural empyema.
AB  - Over a 17 year period, 1975-91, 10 children were managed who had sinusitis
      induced subdural or extradural empyema. Their ages ranged from 6 to 14 years,
      with a mean of 11 years. All presented with worsening headaches, fever, vomiting,
      all had neurological abnormalities, and all had symptoms or signs suggestive of
      sinusitis. Initial computed tomography gave normal results in five cases and the
      empyema was diagnosed on the second or third scan. All patients had symptoms for
      at least one to two weeks before the diagnosis was made. Streptococcus milleri
      was the organism most frequently implicated. Medical treatment was started in all
      cases on admission, but all required surgical intervention before resolution.

PMID- 1362639
TI  - Role of NMDA receptors in the compensation of ocular nystagmus induced by
      hemilabyrinthectomy in the guinea pig.
AB  - The possibility that N-methyl-D-aspartate (NMDA) receptor activation plays a role
      in inducing the vestibular compensation following hemilabyrinthectomy (HL) in
      guinea pigs, was verified by means of continuous intraventricular osmotic pumping
      of DL-2-Amino-5-phosphono-valeric acid (APV). Our results show that high doses
      (40 and 20 mM) of APV decrease both the combined OKR and VOR and the nystagmus
      following HL. Low doses of APV (2.5 mM), affect the time course of the ocular
      compensation by maintaining a higher level of nystagmus beat frequency and by
      delaying the nystagmus disappearance. On the contrary, the compensation time
      course is not affected by administering APV later on in the compensation period.
      Therefore, it appears that NMDA receptors are activated during the precocious
      phase of vestibular compensation, when a large vestibular imbalance is present.
      This finding is explained by the development of NMDA receptor hypersensitivity,
      in the functionally inactivated commissural system or by the occurrence of NMDA
      mediated long-term potentiation.

PMID- 1362637
TI  - Change of glutamic acid to lysine in a 13-residue antibacterial and hemolytic
      peptide results in enhanced antibacterial activity without increase in hemolytic
      activity.
AB  - A 13-residue peptide corresponding to a hydrophobic segment of the antimicrobial
      47-residue peptide seminalplasmin, PKLLETFLSKWIG (SPF), has been shown to have
      antibacterial and hemolytic activities (N. Sitaram and R. Nagaraj, J. Biol. Chem.
      265:10438-10442, 1990). In an effort to get an insight into the structural and
      charge requirements for these biological activities, an analog of SPF in which
      Glu has been replaced with Lys has been synthesized and its antibacterial and
      hemolytic properties have been examined. It has been demonstrated that the
      analog, SPFK, exhibits potent antibacterial activity at concentrations at which
      hemolysis does not occur.

PMID- 1362640
TI  - [The reports of the IIIrd All-Union Educational and Methodological Conference on
      Pathological Anatomy. Moscow, 2-7 December 1991].

PMID- 1362641
TI  - Asthma mortality and over the counter purchase of inhaled beta agonists.

PMID- 1362642
TI  - [RFLP analysis of single hairs].
AB  - Investigations were performed with the root of one hair torn out 6 times in
      parallel. Yield of DNA was about the same with 6 extraction methods tested. Hairs
      stored at RT up to 8 weeks in non sterile environment showed the same result as
      deeply frozen hairs. Hairs of one test person could not be typed in repeated
      investigations, whereas hairs of another person could successfully be typed in
      every case (n > 100). 35 hairs of 66 samples investigated from 11 other persons
      could be typed.

PMID- 1362643
TI  - [Population genetic Hae III/RFLP and HLA-DQ-alpha data of a Caucasian population
      sample in Switzerland].
AB  - DNA from unrelated individuals (Caucasians; n = 200-271) from Switzerland were
      digested with Hae III and successively hybridized to the DNA probes D1S7, D2S44,
      D4S139, D10S28, D14S13, D17S26 and D17S79. An allele frequency distribution was
      determined for each locus. Furthermore, from the same individuals (n = 200) after
      amplification of DNA the allele and genotype frequencies at the HLA-DQ alpha
      locus were determined. The allele frequency distribution in Swiss Caucasians is
      statistically similar to American Caucasian population samples. In criminal cases
      a DNA-profile derived from four single-locus probes always leads to a very high
      value of discrimination and in paternity testing the probability of paternity
      always exceeds 99.9% regardless to the reference population used for
      biostatistical evaluation. Therefore for use in forensic analysis and paternity
      testing pooled caucasian databases might be used for the determination of the
      frequency of occurrence of a DNA-profile.

PMID- 1362644
TI  - [Conversion of forensic paternity determination to DNA analysis].
AB  - For many years, the resolution of disputed paternity cases by genetic means
      relied on laboratory blood tests of red cell antigens and red cell and serum
      protein electrophoresis. These systems are generally characterized as lacking
      polymorphism and having low powers of exclusion, therefore it was necessary to
      use a panel of up to 23 marker systems. Over the past five years, a variety of
      DNA restriction fragment length polymorphism (RFLP) systems have been developed
      that characterize individuals at the DNA level. In this paper we describe the
      implementation of a Hae III RFLP system utilized in our laboratory for the
      resolution of disputed parentage cases as well as forensic casework. Since the
      analysis of highly polymorphic VNTR loci has proven to be the most powerful
      method to date for the determination of biological relatedness the utilization of
      the conventional methodologies should be completely replaced.

PMID- 1362645
TI  - [Effects of nonoxinol 9 on RFLP typing of postcoital vaginal smears].
AB  - Nonoxinol 9 effectively inactivates high titres of HIV in vitro, which suggest
      its use for reducing HIV-transmission via sexual intercourse. Therefore, the
      suggestion has been made for the treatment of sexual assault victims with a
      topical anti-HIV agent such as nonoxinol 9 as soon as possible after a sexual
      assault has occurred. From the forensic point of view it becomes pertinent to
      determine whether or not nonoxinol 9 would have an adverse effect on the high
      molecular weight deoxyribonucleic acid (DNA) in vaginal swabs and thereby impact
      RFLP results. The study demonstrates that nonoxinol 9 does not have a negative
      effect on the ability to produce RFLP patterns. Therefore, the early
      administration of the topical anti-HIV agent nonoxinol 9 has to be considered as
      an important step in the medical treatment of sexual assault victims.

PMID- 1362646
TI  - FMRFamide-related peptides potentiate transmission at the squid giant synapse.
AB  - The stellate ganglion of the squid Loligo pealli contains the neuropeptides Phe
      Met-Arg-Phe-NH2 (FMRFamide), Phe-Leu-Arg-Phe-NH2 (FLRFamide) and at least one N
      terminally extended FMRFamide-related peptide that is yet to be fully
      characterized. Both local application and arterial perfusion of FLRFamide
      potentiate transmission at the giant synapse. The N-terminally related peptide
      Ser-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (SDPFLRFamide) produced a similar effect. The
      threshold for both the tetra- and the hepta-peptides was less than 10 microM.
      Potentiation could be detected as an increase in rate of rise of the EPSPs, as an
      increase in amplitude of the EPSP in the absence of spikes, or under voltage
      clamp as an increase in the EPSC. The effect was most pronounced when the synapse
      was fatigued by high frequency stimulation. Another molluscan peptide, eledoisin
      and also leucine enkephalin were without effect. In the absence of any detectable
      effects of FLRFamide on the resting membrane potential of either pre- or
      postsynaptic terminals or on the presynaptic spike, it is suggested that the
      peptide influences transmitter mobilization. However, the peptide could also
      exert small changes in preterminal calcium currents, which so far we have been
      unable to detect.

PMID- 1362647
TI  - [Nursing Congress 1992].

PMID- 1362648
TI  - A new family of homeobox genes encoding multiple homeodomain and zinc finger
      motifs.

PMID- 1362649
TI  - Ectopic expression of Hox-2.3 induces craniofacial and skeletal malformations in
      transgenic mice.
AB  - To better understand the role of the Hox-2.3 murine homeobox gene during
      development, a dominant gain-of-function mutation was generated. The
      developmental malformations that resulted when the chicken beta-actin promoter
      was used to direct widespread expression of the Hox-2.3 gene in transgenic mice
      included early postnatal death as well as craniofacial abnormalities, including
      open eyes and cleft palate. Ventricular septal defects were also observed in the
      hearts of three transgenic mice. Skeletal malformations were seen in the bones of
      the craniocervical transition, with the occipital, basisphenoid, and atlas bones
      deficient or misshapen. Interestingly, one mutant exhibited an extra pair of ribs
      as well as alterations in cervical vertebrae identities. Some of the
      malformations observed in Hox-2.3 gain-of-function mutants overlap with those
      seen in Hox-1.1 and Hox-2.2 misexpression mutants which suggests functional
      similarities between paralogous homeobox genes. The results of these experiments
      are consistent with a role for Hox-2.3 in specifying positional information
      during development.

PMID- 1362650
TI  - Structure and early embryonic expression of the zebrafish engrailed-2 gene.
AB  - The Drosophila homeobox gene engrailed (en) is needed for correct embryonic
      development, and related sequences are active during vertebrate embryogenesis.
      Here we report the protein coding sequence and embryonic expression pattern of
      the zebrafish engrailed-2 gene (eng-2) which is directly homologous to En-2 in
      mice and Xenopus. The predicted zebrafish Eng-2 protein shares 65% overall
      identity to its Xenopus counterpart. In addition to the highly conserved
      homeodomain region, sequence conservation is present within three short stretches
      in the N-terminal region. The embryonic expression of the eng-2 gene was analysed
      by in situ hybridization to whole-mount embryos and tissue sections. Transcripts
      are first detected in two lateral bands at the 10-h stage, when epiboly is
      completed. Within the next 2 h of development, these two bands migrate and fuse
      at the midline. By the time the neural keel becomes visible (11-12 h), a
      transverse stripe of eng-2 expressing cells is seen at the presumptive midbrain
      hindbrain boundary. Later this stripe becomes significantly compressed along the
      AP axis, and in 24-h embryos eng-2 transcripts are detected mainly in the
      posterior midbrain. In the hindbrain, eng-2 expression seems restricted to the
      primordium of the cerebellum. A second site of activity was observed in each
      somite where specific myotomal cells, the muscle pioneers, express eng-2. Our
      observations are discussed in relation to early regionalization of the central
      nervous system (CNS) and the generation of morphological borders.

PMID- 1362651
TI  - A cis-element mediating Ultrabithorax autoregulation in the central nervous
      system.
AB  - We dissected an upstream control region (a BXD fragment) from the homeotic gene
      Ultrabithorax (Ubx) of Drosophila which confers a Ubx-like expression pattern in
      the embryonic ectoderm. We found several distinct enhancer elements spread
      through the whole BXD fragment each of which is active in transformed embryos,
      mediating a different pattern of beta-galactosidase expression in the ventral
      nerve cord. The strongest of these patterns mimics Ubx expression within the Ubx
      domain. This pattern is strictly dependent on Ubx function. Thus, the BXD control
      region contains a Ubx response element, suggesting that positive autoregulation
      of Ubx may occur in the central nervous system of the developing embryo.

PMID- 1362652
TI  - Transcriptional regulation of the germline immunoglobulin C alpha and C epsilon
      genes: implications for commitment to an isotype switch.
AB  - Lymphokine directed isotype switching is preceded by the induced expression of
      the corresponding germline Ig heavy chain constant region (CH) gene. This
      association favors a model in which lymphokine induced germline CH gene
      expression promotes switch recombination by increasing the accessibility of the
      switch region to a recombinase(s). An important prediction of this model is that
      the induction of germline CH RNAs represents increased specific de novo
      transcription. To test if this prediction is fulfilled by the switch commitment
      factors, IL-4 and transforming growth factor-beta (TGF-beta), we have utilized a
      B cell line, 1.29, that switches from IgM to IgE and IgA in vitro. In this cell
      line, IL-4 and TGF-beta increase germline C epsilon and C alpha RNA levels
      respectively, predominantly by elevating transcription of these genes.
      Transcription of germline C epsilon and C alpha genes appears to be independently
      regulated and is not affected by lipopolysaccharide or IL-5. These results are
      discussed in the context of the molecular events necessary to commit a B cell to
      an isotype switch.

PMID- 1362654
TI  - [The role of ATPase activity in the function of molecular chaperones and some
      regulatory proteins].
AB  - It has been suggested that the ATPase activity of molecular chaperones depends on
      the structure of the recognizable determinant in the target protein. The role of
      molecular chaperones in polypeptide chain folding and protein association into
      oligomeric complexes is discussed. The putative regulatory role of the
      determinant ATPase activity of molecular chaperones and those of some regulatory
      proteins are discussed. A hypothesis is proposed that determinant ATPases play a
      part in the increasing specificity of intermacromolecular interactions.

PMID- 1362655
TI  - Quantitative determination of natriuretic peptides in human biological samples
      with a bioassay using cultured cells.
AB  - Up to now, members of the natriuretic peptide family have usually been determined
      by radioimmunoassays using antibodies more or less specific for the distinct
      peptides so far identified. However, natriuretic peptides differing significantly
      in their amino acid sequence from the one against which the antibody has been
      raised cannot be determined by this means, and still unknown natriuretic peptides
      cannot be detected. We therefore developed a new bioassay system sensitive to all
      members of the natriuretic peptide family by taking advantage of the biological
      activity of these hormones, the activation of the guanylate cyclase/cyclic GMP
      system. In this assay, cultured cells are incubated with the natriuretic
      peptides, and the amount of cyclic GMP produced by the cells is determined by
      radioimmunoassay. From the relative stimulation of the cellular cyclic GMP
      production, the concentration of natriuretic peptides in the sample is determined
      after calibration with synthetic atrial natriuretic peptide. For a qualitative
      identification of the various peptides, the bioassay is combined with a reversed
      phase HPLC step. Using cultured bovine aortic endothelial or bovine kidney
      epithelial cells for the bioassay, we achieved detection limits of 1 fmol or 50
      fmol, respectively, for human atrial as well as brain natriuretic peptide. Intra
      assay coefficients of variation of 4.3% (aortic endothelial cells, at 0.65 nmol/l
      peptide) and 5.8% (kidney epithelial cells, at 6.5 nmol/l peptide) were obtained.
      The total content of natriuretic peptides as well as the amounts of the
      individual natriuretic peptides following HPLC separation were determined in
      extracts of human atria obtained at aortocoronary bypass operations.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1362656
TI  - Pharmacokinetics of oxatomide given percutaneously to healthy volunteers.
AB  - The percutaneous absorption of oxatomide gel at 5 per cent concentration was
      studied after single and repeated administration (85 mg b.i.d.) in six male and
      six female healthy volunteers, aged 25.7 +/- 0.8 years (mean +/- SEM) weighing
      64.4 +/- 4.5 kg and the results compared with those obtained following a single
      oral dose (30 mg). The measurement of oxatomide was by means of a new sensitive
      and specific HPLC assay with limits of detection of 0.2 ng ml-1 in plasma and 1.0
      ng ml-1 in urine. Poor percutaneous absorption was confirmed by the peak plasma
      concentrations which were 5.03 +/- 0.79 ng ml-1 following application of the gel
      for 7 days and 10.08 +/- 1.29 ng ml-1 following oral administration; the
      corresponding amounts of unchanged oxatomide recovered from 24 h urine
      collections were 1.42 +/- 0.39 micrograms and 3.93 +/- 0.92 micrograms.

PMID- 1362653
TI  - Insights into the mechanisms of action of the MAO inhibitors phenelzine and
      tranylcypromine: a review.
AB  - Although the non-selective monoamine oxidase inhibitors phenelzine and
      tranylcypromine have been used for many years, much still remains to be
      understood about their mechanisms of action. Other factors, in addition to the
      inhibition of monoamine oxidase and the subsequent elevation of brain levels of
      the catecholamines and 5-hydroxytryptamine, may contribute to the overall
      pharmacological profiles of these drugs. This review also considers the effects
      on brain levels of amino acids and trace amines, uptake and release of
      neurotransmitter amines at nerve terminals, receptors for amino acids and amines,
      and enzymes other than monoamine oxidase, including enzymes involved in
      metabolism of other drugs. The possible contributions of metabolism and
      stereochemistry to the actions of these monoamine oxidase inhibitors are
      discussed.

PMID- 1362658
TI  - First conference on antisense DNA and RNA in Japan.

PMID- 1362659
TI  - About the centrality of mood lowering in mood disorders. Plenary Lecture ECNP
      Congress, Monte Carlo, October 1991.
AB  - 5-HT disturbances in depression (as exemplified by lowered CSF 5-HIAA) are not
      syndrome specific but related to components of the depressive syndrome,
      specifically to increased anxiety and aggression. These 5-HT disturbances are
      probably core pathogenetic processes not derivative features. I hypothesized that
      in this subtype of depression, i.e. in "5-HT related depression", the key
      psychopathological disturbances are dysregulation of anxiety and aggression,
      while mood lowering is a "by-product". Based on this hypothesis it was predicted
      that agents which ameliorate anxiety and/or aggression via harmonization of 5-HT
      ergic transmission will, in addition, exert overall antidepressant effect in "5
      HT related depression". The study of the relative "weight" of the various
      psychopathological components of depression is a basic exercise in understanding
      the nature of that condition and could, as such, greatly facilitate the goal
      directed search for new and innovative antidepressants.

PMID- 1362657
TI  - Factors predicting early response to treatment with recombinant interferon alpha
      2a in chronic non-A, non-B hepatitis. Preliminary report of a long-term trial.
AB  - To evaluate cost-effectiveness and response predictors of treatment with
      recombinant interferon alpha-2a in chronic non-A, non-B hepatitis, 263
      consecutive patients were enrolled in a multicenter long-term study. A pre
      planned analysis aimed at identifying predictors of early response was carried
      out when all patients had completed the initial 3 months of treatment with 6 MU
      thrice weekly. Sixty-three percent of the patients enrolled were classified as
      responders. At multivariate logistic regression analysis, baseline gamma
      glutamyltranspeptidase levels and cirrhosis were the only independent variables
      significantly associated with response. The risk of no response after 3 months of
      treatment was 3.9 times higher (95% confidence interval, 1.6 to 7.2) in patients
      with high baseline levels of gamma-glutamyltranspeptidase as compared with
      patients showing low baseline levels, and it was 2.0 times higher (1.1 to 3.8) in
      patients with cirrhosis as compared with those without it. We expect that results
      from this and other studies on large patient populations may help to select those
      patients who are more likely to benefit from interferon administration.

PMID- 1362660
TI  - Lack of effect of chronic antipsychotic treatment on dopamine D5 receptor mRNA
      level.
AB  - The effects of administration of antipsychotic drugs (haloperidol, loxapine,
      sulpiride; 1-32 day time course) on the rat brain mRNA levels of the dopamine D5
      receptor has been assessed using solution hybridisation with oligonucleotides. In
      contrast with the previously reported increases of D1, D2 and D3 receptor mRNA
      levels in identical experiments, no changes were found in dopamine D5 receptor
      mRNA levels, suggesting that the mechanism of regulation of D5 receptor mRNA is
      different to the other cloned dopamine receptors. We also conclude that up
      regulation of the D5 receptor is not likely to be involved in the mechanism of
      action of antipsychotic drugs.

PMID- 1362661
TI  - Benzodiazepines preferentially affect mesolimbic dopamine turnover in rats.
AB  - Withdrawal of benzodiazepines in man may induce hallucinatory symptoms and can
      evoke delusional depressions, which can be treated with dopamine-antagonistic
      drugs. Withdrawal of benzodiazepines in rats induces a strong hyperactivity
      during daytime, leaving the nighttime activity relatively undisturbed. This
      hyperactivity may be related to an enhanced dopaminergic activity in the
      mesolimbic area, especially in the nucleus accumbens. Mesolimbic dopaminergic
      activity may be specifically involved in the development of benzodiazepine
      withdrawal. Acute administration of benzodiazepines in otherwise non-treated
      rats, has been described not to affect the dopamine-turnover in the nucleus
      accumbens, measured by synthesis inhibition. However, activation by
      administration of haloperidol (feedback activation) can be suppressed by
      benzodiazepines effectively. Five different benzodiazepines viz.
      desmethyldiazepam (DMD), lorazepam (LRZ), brotizolam (BTZ), triazolam (TRZ) and
      flunitrazepam (FNZ) have been compared with respect to their acute effects. Using
      a 3-fold increase in dopamine turnover (determined by measuring the DOPAC
      concentration), benzodiazepines were capable to reduce this increase maximally
      for 70-80% in the nucleus accumbens. The results point to a selective effect of
      benzodiazepines in the nucleus accumbens. The increase induced by haloperidol in
      the corpus striatum was found to be much less sensitive to benzodiazepines. In
      contrast to the other compounds lorazepam appeared to have no effect on
      haloperidol-induced increase in DOPAC concentration. Flunitrazepam and brotizolam
      did affect not only the haloperidol-induced DOPAC increase but also the basal
      DOPAC concentrations. Linear dose-response curves could not be obtained for the
      compounds, but minimal effective doses could be assessed. Flunitrazepam and
      triazolam appeared to be the most active compounds.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1362662
TI  - Mode of action of the triazolobenzodiazepines in the treatment of panic attacks:
      a hypothesis.
AB  - Alprazolam (Xanax) or 8-chloro-1-methyl-6-phenyl-4H-S-triazolobenzodiazepine is a
      potent drug for the treatment of anxiety disorders. The chemical structure
      differs from the classical benzodiazepines by incorporation of the triazoloring.
      Due to the triazolo ring, the drug can have additional modes of action than the
      normal benzodiazepines. The triazolobenzodiazepines are potent inhibitors of the
      platelet-activating factor. This factor is a potent stimulator of the
      corticotropin-releasing hormone. This hormone has an effect on the hypothalamo
      pituitary-adrenal axis but the corticotropin-releasing hormone is also known to
      be a stimulator of the locus coeruleus. The corticotropin-releasing hormone in
      patients with panic attacks is elevated. This could be a result of the
      hyperactive metabolism which is observed by positron emission tomographic (PET)
      studies of the right parahippocampal area.

PMID- 1362663
TI  - Expression of glutathione transferase pi in benign and malignant lesions of the
      melanocyte lineage.
AB  - Intrinsic and acquired resistance to chemotherapeutic agents represents the major
      clinical obstacle in the control of most tumours. In vitro studies have
      established that multiple mechanisms, including changes in drug uptake and efflux
      and in detoxifying enzymes, are responsible for drug resistance. Among the
      latter, glutathione S transferases (GST) have been recognized to play a relevant
      role. In the present study we have evaluated GST pi immunohistochemically as well
      as enzymatically in benign and malignant primary and metastatic lesions of the
      melanocyte lineage. A parallel analysis of the multiple drug resistance (MDRI)
      gene product was performed in a representative number of specimens. Results of
      this study demonstrate that while GST pi is constitutively expressed by the
      melanocyte lineage, independently from the transformed stage, MDRI p-glycoprotein
      is detected with a significantly lower frequency. These findings clearly indicate
      that GST pi represents the major detoxifying metabolic pathway of the melanocyte
      lineage and may be responsible for the high degree of inherent resistance of
      malignant melanoma to available cytostatic treatments.

PMID- 1362664
TI  - Combined cornual pregnancy and intrauterine twin pregnancy after in vitro
      fertilization and embryo transfer: report of a case.
AB  - A case of combined cornual pregnancy and intrauterine twin pregnancy after in
      vitro fertilization (IVF) and transfer of six embryos is presented. The case was
      diagnosed as intrauterine triplets ultrasonographically at seven weeks of
      gestation. Unfortunately, the patient suffered from severe lower abdominal pain
      and hypovolemic shock at 10 weeks of gestation, and an emergent laparotomy was
      done. During the operation, a ruptured cornual pregnancy with accompanying
      hemoperitoneum was found. Because fetal heart beats were not detected by
      intraoperative ultrasonography in the other two intrauterine fetuses, evacuation
      of the gestational contents through the uterine defect was done, and the rupture
      site was repaired. The incidence, mechanism and management of heterotopic
      pregnancies after in vitro fertilization and embryo transfer are discussed.

PMID- 1362665
TI  - Bizarre parosteal osteochondromatous proliferation of the phalanx: report of a
      case.
AB  - The bizarre parosteal osteochondromatous proliferation of the hand and foot is a
      benign lesion which occasionally may mimic osteochondromas, chondrosarcomas or
      osteosarcomas clinically, radiologically and histopathologically. This rare
      benign entity should be recognized in order to avoid unwarranted destructive
      therapy. The authors report a case of this disease and discuss the differential
      diagnosis and the relevant features of this disease entity. A 27-year-old female
      patient suffered from a painful swelling at the proximal middle phalanx of the
      right middle finger for five months. The lesion was excised but the residual
      lesion developed a distinct parosteal growth by radiologic studies one-and-a-half
      years later. The patient underwent reexcision of the lesion twice. No recurrence
      was noted 11 months following the last excision. Histopathologically, the first
      specimen contained bizarre chondrocytes. The recurrent nodular tumors, submitted
      in the second and third operations, were composed of cancellous bone with fatty
      marrow and a few marrow elements, and focally capped by cartilage. The adjacent
      soft tissue contained proliferating fibrous tissue. The osteochondral junctions
      in the latter two specimens were irregular. We believe that the documentation of
      this tumor at different stages of development has helped in the further
      understanding of this rare entity.

PMID- 1362666
TI  - Solitary cerebellar metastases: analysis of 11 cases.
AB  - Solitary cerebellar metastatic tumors are rarely reported in the literature. We
      reviewed 240 posterior fossa tumors treated in the past eight years. There were
      11 cases of solitary metastases in the cerebellum. The primary tumor was lung
      cancer in five cases and breast carcinoma in two cases; the remaining three cases
      had colon cancer, nasopharyngeal carcinoma (NPC) and Ewing's sarcoma,
      respectively. All patients underwent craniectomy and gross total excision of the
      tumor. Seven patients survived less than one year, two cases died in the second
      year, and one case of NPC survived for more than two years. The only survival is
      a case of Ewing's sarcoma who underwent surgery 14 months ago. The symptoms and
      signs of all patients improved satisfactorily after surgery. Four patients
      received postoperative irradiation to the posterior fossa and two cases of lung
      cancer had a thoracotomy for the primary lung lesion; however, the survival
      period was not prolonged. We suggest that a cancer patient or a patient in the
      fifth to seventh decades of life presenting headache, gait disturbance and
      vomiting should promptly undergo a computed tomography (CT) scan of the head. In
      selected cases, surgical intervention for solitary metastatic tumors in the tiny
      posterior fossa may be the best initial treatment. Adjuvant therapies should then
      be added according to the type of tumor.

PMID- 1362667
TI  - Delayed-onset dystonia following recovery from central pontine myelinolysis.
AB  - We report on a 47-year-old female patient with Sheehan's syndrome who developed
      delayed-onset dystonia following recovery from central pontine myelinolysis. The
      dystonia was observed in the head, neck and limbs during active movement. MRI
      scan demonstrated a discrete lesion in the central pons without involving the
      basal ganglia. The action dystonia was markedly improved by giving
      trihexyphenidyl. The patient showed that generalized dystonia can be induced by
      an isolated pontine myelinolysis. There have been four other cases reported in
      the literature. On reviewing all five cases, we conclude that delayed-onset
      dystonia following central pontine myelinolysis usually presents with generalized
      action dystonia and has a beneficial response to trihexyphenidyl.

PMID- 1362668
TI  - Hypothalamic hamartoma and precocious puberty: report of a case.
AB  - Hypothalamic hamartoma is reported to be associated with precocious puberty.
      Here, the authors present a seven-year-old girl whose onset of puberty occurred
      at the age of two. Under the impression of idiopathic precocious puberty,
      cyproterone acetate was initially tried. Since the effect of her medication was
      not satisfactory, it was discontinued at the age of five years and 11 months.
      However, rapid advance of bone age and vaginal spotting recurred after the
      withdrawal of treatment. She was re-evaluated at the age of six, and a magnetic
      resonance image (MRI) study of the head revealed a hypothalamic hamartoma. At
      that time, a long-acting analog of luteinizing hormone-releasing hormone (LHRHa),
      leuprolide acetate, was prescribed. Her secondary sex characteristics regressed
      and her hypothalamic-pituitary-gonad axis was suppressed after treatment. The
      clinical presentation, mechanism and treatment of precocious puberty caused by
      hypothalamic hamartomas are fully discussed in this report.

PMID- 1362669
TI  - Simultaneous presence of three or more creatine kinase isoenzymes in patient
      serum.
AB  - Samples of sera from 1,508 consecutive patients, which were sent to the clinical
      laboratories of Chang Gung Medical College for creatine kinase (CK) isoenzyme
      determination, were examined for the simultaneous presence of various patterns of
      three or more usual or atypical isoenzymes. Of these samples, a total of 29 cases
      (1.9%) exhibited this abnormal isoenzyme condition. Nineteen (66%) of these 29
      cases were patients with cancer of various types. Furthermore, five (26%) of
      these 19 cases had the same pattern of four isoenzymes, and 17 (89%) of these 19
      cases showed the cathodic CK variant (macro CK type II). Eleven (58%) of these 19
      cancerous cases also showed a CK-MB variant, evidently of nonmyocardial origin.

PMID- 1362670
TI  - Cancer of the colon during pregnancy: report of a case and review of the
      literature.
AB  - A case of adenocarcinoma of the sigmoid colon during pregnancy is reported. The
      patient presented with anemia and a painless mass over the left abdomen without
      gastrointestinal discomfort, making this case different from 25 previously
      reported cases of colon carcinoma above the peritoneal reflection associated with
      pregnancy.

PMID- 1362671
TI  - Pen injector for insulin-requiring diabetic patients.
AB  - To compare the metabolic control and acceptability of a pen injector to the
      traditional syringe used in diabetes, 12 non-insulin-dependent diabetes mellitus
      (NIDDM) patients and six insulin-dependent diabetes mellitus (IDDM) patients were
      followed-up at the outpatient clinic of the Taipei Municipal Yang-Ming Hospital.
      All patients participated in a four-week run-in period and 24-week randomized
      cross-over design study. Human NPH insulin (Protaphane HM) in vials and in
      penfills were used in each 12-week experimental period, respectively. Metabolic
      control was assessed by a biochemical examination (before and after seven months
      of treatment) and HbA1c levels (at Weeks 1, 4, 16 and 28) and was found to be
      unchanged. The overall mean blood glucose declined slightly in both treatment
      modalities but not to a significant level (mean +/- SE; run-in: 175 mg/dL +/- 10
      mg/dL; pen: 159 mg/dL +/- 8 mg/dL; syringe: 156 mg/dL +/- 7 mg/dL). The number of
      hypoglycemic episodes and self-adjustments of insulin dosage did not differ
      significantly between pen and syringe treatments. At the end of the study, a
      questionnaire revealed that eight patients would choose pen injectors, nine
      patients syringes and one was unsure of what to use as a future preference. The
      limitation of 36 units per injection of insulin is a drawback for those NIDDM
      patients with insulin resistance. An insulin delivery device that would allow an
      injection of a larger quantity of insulin is desirable for some patients.

PMID- 1362672
TI  - Epidemiologic investigation of nosocomial outbreak of methicillin-resistant
      Staphylococcus aureus by plasmid pattern analysis.
AB  - Nosocomial infections caused by methicillin-resistant Staphylococcus aureus
      (MRSA) have become an important problem with increasing frequency. In order to
      learn if plasmid pattern analysis can be used in epidemiologic investigations of
      MRSA infections, the authors did plasmid extractions of 70 MRSA stock isolates
      using a rapid lysostaphin lysis method. All isolates carried at least one
      plasmid. Most of the isolates had one large plasmid of 24-28 megadaltons (Md).
      Many also carried one or two small plasmids. Accordingly, 12 different patterns
      were identified. From these background results, we applied this method to the
      investigation of two small nosocomial outbreaks of MRSA infection. It was found
      that the analysis of plasmid pattern and restriction endonuclease analysis are
      more discriminative than antibiograms. Strains with the same antibiograms can be
      different by plasmid analysis. It is concluded that the plasmid pattern with a
      restriction endonuclease analysis study is a reliable method for epidemiologic
      study of MRSA infections.

PMID- 1362673
TI  - Dystrophin gene deletion in Chinese Duchenne/Becker muscular dystrophy patients
      via multiplex DNA amplification.
AB  - Duchenne/Becker muscular dystrophy (DMD/BMD) is a progressive muscle-wasting
      disease. The dystrophin gene responsible for the disease is the largest human
      gene ever cloned and is prone to gross gene deletion in two "hot spot" regions.
      Using nine pairs of oligonucleotide primers deduced from the two regions, we have
      screened 23 unrelated Chinese DMD/BMD patients by multiplex polymerase chain
      reaction. Nine (39%) patients were noted to have gene deletion, one in the 5'
      terminus and eight in the distal half of the gene. The incidence is similar to
      that reported in other large series mainly on Caucasian patients. The "hot-spot"
      regions also seem to be present in Chinese patients. Multiplex gene amplification
      for deletion analysis is useful in the diagnosis of patients with neuromuscular
      diseases and is an important aid in the prenatal diagnosis and genetic counseling
      of at-risk families.

PMID- 1362674
TI  - Role of platelets in microembolism-induced acute lung injury.
AB  - The role of platelets in acute lung injury has not been well defined. In the
      present study of isolated perfused rat lungs, a significant increase in pulmonary
      arterial pressure (PAP), lung weight and the lung lavage fluid protein
      concentration occurred when 3 mL of a CaCl2 suspension (25 mg/mL) was mixed with
      blood-KHB (Krebs-Henseleit Buffer) perfusate; or when platelets were added
      instead of blood. However, such an increase was not observed (p > 0.05) when only
      KHB was used. When a comparatively small amount (0.75 mL) of the CaCl2 suspension
      (50 mg/mL) was added to the KHB perfusate, PAP, lung weight and the lung lavage
      protein concentration increased only when PAF (platelet activating factor) and
      platelets were both added before, but not separately. The above phenomena show
      that platelets are actively involved in the mechanism of acute lung injury and
      play an extremely important role in this microembolic model.

PMID- 1362675
TI  - Experience of desmopressin (DDAVP) administration in patients with congenital and
      acquired bleeding disorders.
AB  - Desmopressin (DDAVP) 0.3 micrograms/kg was administered intravenously to three
      normal volunteers and 12 patients with von Willebrand's disease (vWD), congenital
      or acquired platelet function defect, or uremic bleeding to assess its effects
      and side effects. DDAVP significantly shortened the bleeding time as compared
      with basal values. The mean peak post-DDAVP level of factor VIII coagulant
      activity increased 5.9 +/- 0.5 (mean +/- SEM) fold, von Willebrand factor antigen
      increased 3.7 +/- 0.3 fold, von Willebrand factor ristocetin cofactor activity
      increased 4.6 +/- 0.6 fold and the tissue-type plasminogen activator antigen
      increased 3.4 +/- 0.6 fold. Analysis of the multimeric structure of the von
      Willebrand factor revealed that type I vWD had complete correction after DDAVP
      infusion transiently. Except for a mild drop in both systolic and diastolic blood
      pressures, few side effects were noted. By concomitant intravenous infusion of
      DDAVP and oral administration of tranexamic acid, we successfully treated two
      cases of type I vWD undergoing tooth extraction, and one case of acquired
      bleeding disorder undergoing a biopsy of a mandibular mass, and a uremic patient
      complicated by intractable traumatic hematuria. Our experiences confirmed that
      most patients with vWD and some patients with congenital or acquired bleeding
      disorders can be treated effectively by DDAVP infusion without the need for
      plasma product replacement. In this study we found that a patient with a variant
      form of type I vWD had prolongation of the bleeding time, thrombocytopenia and
      platelet aggregation after DDAVP infusion.

PMID- 1362676
TI  - Prevalence of goiters in school children residing in villages where underground
      water is used.
AB  - A representative of Fuder village in Taichung County complained that many
      residents had a goiter problem, which he felt might be related to pollution from
      the nearby Youshi industrial area. The purpose of this study was to determine
      whether school children in the Fuder area have a high prevalence of goiters. We
      chose children of the Schichi elementary school in the Fuder area as the study
      population, and children of the Goumei elementary school, far from the Youshi
      industrial area, as controls. Both groups were from a similar geographic location
      (near the sea), had similar socioeconomic status, and both drank underground
      water. Thyroid enlargement was examined by palpation as recommended by the World
      Health Organization. Thyroid antibodies and hormones were determined in school
      children with a goiter and age-sex-matched normal control children using the
      particle agglutination method and radioimmunoassay, respectively. In total, 1,692
      school children were examined, including 875 males and 817 females. Of these, 126
      school children (7.4%) had a goiter of Grade I or above. The prevalence of
      goiters in Shichi and Goumei were 8.8% (59/671) and 6.6% (67/1,021),
      respectively. There was no significant difference between these two areas. We
      compared the prevalence of goiters in these two schools where underground water
      is drunk with another previous study in Peimen and Putai where tap water is used.
      There was a statistically significant difference (7.4% vs 2.6%, p < 0.0001). This
      suggests that the higher prevalence rate of goiters in Shichi and Goumei is
      related to the drinking of underground water. We recommend that the use of tap
      water and continued salt iodization is the way to prevent endemic goiter in these
      areas. A further comprehensive study is needed to determine the nature of the
      goitrogen in the underground drinking water of the Fuder area.

PMID- 1362677
TI  - Multiplanar gradient recalled images of the knee: comparison of different flip
      angles and echo times.
AB  - To determine the most appropriate combination of echo time (TE) and flip angle in
      gradient echo images of the knee, the authors used different TEs (10, 20 and 30
      msec) and flip angles (10, 30, 50, 70, 90, 120 and 150 degrees) to perform a
      systematic study of MRI on 10 volunteer knees. Contrast-to-noise ratios of
      cartilage-fat, fluid-cartilage, fluid-fat and fluid-ligament were calculated and
      compared. Images with a 30-degree flip angle combined with 20 msec of TE were
      found to have the best contrast-to-noise ratios in both objective data analysis
      and subjective observation. Hyaline cartilage of the knee was hyperintense and
      was well delineated on this pulse sequence, appearing distinct in contrast to the
      intra-articular fluid. It is concluded that this T2-weighted gradient echo pulse
      sequence is an alternative to conventional spin echo T2-weighted imaging of the
      knee.

PMID- 1362678
TI  - Staging of cervical cancer: comparison between magnetic resonance imaging,
      computed tomography and pelvic examination under anesthesia.
AB  - A prospective study was undertaken to compare magnetic resonance imaging (MRI)
      with computed tomography (CT) and examination under anesthesia (EUA) in staging
      cervical carcinoma, with special emphasis on parametrial status. Twenty patients
      with carcinoma of the cervix, in whom the extent of the disease was surgically
      confirmed, were analyzed by MRI, CT and EUA. The tumor size estimated by MRI
      correlated well (r = 0.79, p < 0.001) with those obtained by histopathologic
      measurement of the surgical specimen. Neither clinical examination nor CT could
      precisely estimate tumor size. The overall accuracy rate of MRI in staging
      carcinoma of the cervix was 75%, compared with 32% for CT staging and 55% for
      clinical staging. The accuracy rate of these modalities for parametrial status
      was 90% for MRI, 55% for CT and 82.5% for EUA. MRI accurately excluded all 20
      patients with pelvic side wall, bladder and rectal involvement. In conclusion,
      MRI is superior to CT and EUA in assessment of the parametrium (90% vs 55% vs
      82.5%, p < 0.005). From MRI, tumor size can be estimated precisely. Although a
      larger scale study comparing MRI and CT is needed to determine their roles, both
      should help in the diagnosis and selection of proper treatment for cervical
      carcinoma. Our preliminary report agrees with previous reports that MRI is
      promising and indispensable. MRI should be routinely used in conjunction with
      clinical staging to determine appropriate therapy in patients with cervical
      carcinoma.

PMID- 1362680
TI  - Successful treatment of cytomegalovirus pneumonitis with ganciclovir and high
      dose intravenous immunoglobulin in a bone marrow transplant recipient.
AB  - A 35-year-old man with acute lymphoblastic leukemia in second remission received
      an allogeneic bone marrow transplant from an HLA-compatible sibling donor.
      Unfortunately, cytomegalovirus (CMV) pneumonitis was histologically documented on
      Day +72. Combination therapy with ganciclovir (9-[2-hydroxy-1-(hydroxy-methyl)
      ethoxymethyl] guanine) and high-dose intravenous immunoglobulin (IVIG) was
      started immediately. The treatment comprised a three-week induction course
      (ganciclovir, 2.5 mg/kg q8h and IVIG, 500 mg/kg qod) and a seven-week fixed-dose
      maintenance course (ganciclovir 5 mg/kg thrice a week for 20 doses and IVIG 500
      mg/kg twice a week for eight doses). The pneumonia resolved gradually, and he was
      free from symptoms within two weeks. The only significant side effect was
      moderately severe myelosuppression which was reversible after discontinuation of
      ganciclovir. The patient had a relapse of leukemia on Day +186, but there was no
      recurrence of CMV pneumonitis. This result confirms that such combination therapy
      is effective in the treatment of CMV pneumonitis in a patient with a bone marrow
      transplant.

PMID- 1362679
TI  - Surgery for malignant involvement of the superior vena cava.
AB  - This study reviews surgical operations on seven patients with intrathoracic
      tumors involving the superior vena cava (SVC). Among these patients, five were
      found to have advanced bronchogenic carcinoma; one was found to have thyroid
      carcinoma; and another was found to have thymic carcinoma. The incidence of SVC
      involvement in resectable lung cancer patients at the National Cheng-Kung
      University Hospital was 5.8% (5/85). Total excision of SVC was done in three
      patients and three different prostheses (ringed GoreTex, woven Dacron and
      pericardial tube graft) were interposed. Four patients underwent partial excision
      and repair: one by direct suture and three by autologous pericardial patch. A
      temporary SVC-right atrium internal shunt was used in two of these seven
      patients. The mean time of SVC cross-clamping in five patients was 20 minutes (10
      28 minutes), and the mean value of the central venous pressure at the time of SVC
      cross-clamping was 34 mmHg (18-54 mmHg). There were no operative deaths or
      neurologic sequels. Venography or computed tomography obtained 7-100 days after
      surgery demonstrated all but one to be patent. In conclusion, SVC reconstruction
      with concomitant tumor resection can be performed if a patient fulfills the
      following criteria: 1) there is no distant metastasis; 2) a radiosensitive or
      chemotherapy-effective tumor has been ruled out; and 3) total SVC occlusion or
      prominent collateral circulation should be avoided.

PMID- 1362681
TI  - Lung dysfunction in animal confinement workers--chairman's report to the
      Scientific Committee of the Third International Symposium: issues in health,
      safety and agriculture, held in Saskatoon, Saskatchewan, Canada, May 10-15, 1992.
AB  - The session traced the course of health hazards in livestock confinement from
      anticipation of an emerging health hazard in 1974 to its full recognition as a
      significant health hazard in 1992. The session documented the major health
      hazards including hydrogen sulfide toxicity, bronchitis, non-allergic asthma,
      organic dust toxic syndrome, and mucus membrane irritation. In regard to
      exposures, bioaerosols seem to be the most significant hazard, with endotoxin
      evident as at least one of the major specific atiologic agents. Other agents were
      suspected, as newly recognized agents, specifically 1,3 beta-glucan. Previous
      epidemiological studies have revealed mild decrements in pulmonary function,
      however symptoms have always been excessively prevalent relative to controls.
      Recent results of a longitudinal observation showed a 12% drop out of workers
      with profound decrement in pulmonary function. In summary, the health hazard of
      livestock confinement workers is now well substantiated in North America and
      Europe and further work regarding prevention is highly indicated.

PMID- 1362682
TI  - The pathogenesis of AIDS lymphomas: a foundation for addressing the challenges of
      therapy and prevention.
AB  - The association between AIDS and a spectrum of malignancies relates to chronic,
      profound defects in both cellular and humoral mechanisms of immune surveillance.
      Ironically, as AIDS patients live longer in response to increasingly effective
      antiretroviral therapies, the incidence of AIDS-related malignancies will
      continue to rise. The emergence of non-Hodgkin's lymphomas (NHL) as a major
      sequela of HIV infection bears a striking relationship to depletion of CD4
      lymphocytes, particularly below 50/mm3. The ability to interfere early in the
      course of active HIV infection with additional mechanisms that may promulgate
      transformed cell hyperproliferation and clonal expansion--growth factors, HIV
      itself or other viruses (Epstein-Barr, in particular), aberrant oncogene or tumor
      suppressor genes expression, factors that induce genetic instability or DNA
      damage or alter host or viral genome repair--might decrease the occurrence or
      prolong the time to development of AIDS-related malignancies. The development of
      antiretroviral strategies that confer long-term suppression of HIV activity and
      relative preservation of immune function are essential to the ultimate prevention
      of malignancies that arise as a consequence of HIV-induced immunosuppression.

PMID- 1362683
TI  - Ligation-mediated PCR of restriction fragments from large DNA molecules.
AB  - A general method is described for PCR amplification of single restriction
      fragments from large DNA molecules. The method involves sequence-specific
      ligation of synthetic oligonucleotides to ambiguous 4-base 5' overhangs produced
      by type IIS restriction endonucleases. Such "adapter-tags" provide one target for
      primer annealing in subsequent PCR reactions. The second target for primer
      annealing is provided by a universal "bubble-tag" ligated to blunt ends produced
      with another endonuclease. The key advantage of this approach is that specific
      fragments can be isolated without any prior knowledge of the nucleotide sequence
      of the target. Using bacteriophage lambda DNA as a test system, unique PCR
      products could be generated consistently. Conditions of temperature, ionic
      strength, and substrate concentration in the adapter-tag ligations--which affect
      sequence specificity--were found to have a major influence on the purity of PCR
      generated fragments. In principle, the method permits the amplification of
      virtually any sequence from purified cosmid or YAC DNA using a library of only
      240 adapter-tags.

PMID- 1362684
TI  - Amplification and cloning of sugarcane sucrose synthase cDNA by anchored PCR.
AB  - We have used a strategy based on the polymerase chain reaction (PCR) to amplify
      and construct full-length sucrose synthase (SS) cDNA of sugarcane. Two SS
      specific internal primers were synthesized based on their complementarity to
      published consensus sequences of the SS gene of maize and wheat. Amplification of
      full-length cDNA was achieved by an anchored PCR method utilizing primers which
      extend to 5' and 3' ends of specific cDNA. In the first step, a homopolymeric
      oligo(dC) tail was added to the 3' end of single-stranded cDNAs. The two SS cDNAs
      were amplified, one with a 5' end (SSp1) and the other with a 3' end (SSp2) using
      one internal SS primer and the other anchored end primer. Finally, overlapping
      fragments were identified by restriction mapping, and the non-overlapping
      fragments were excised and religated to reconstruct full-length cDNA. Partial
      sequences of the reconstructed cDNAs (SS-5' and SS-3') were compared with the
      published SS sequences to confirm that the amplified DNA was a copy of the SS
      transcript.

PMID- 1362685
TI  - Cutaneous toxicity of high-dose carboplatin, etoposide and ifosfamide followed by
      autologous stem cell reinfusion.
AB  - Forty patients with germ cell tumors were treated with carboplatin 1500-2000
      mg/m2, etoposide 1200-1600 mg/m2 and ifosfamide 0-10 g/m2 plus mesna followed by
      autologous stem cell reinfusion. A pruritic maculopapular rash was observed in 10
      patients usually starting on the last day of chemotherapy. Lesions remained
      localized to the extremities in four patients. In six they became confluent and
      progressed also involving the trunk and face. Facial edema and painful swelling
      of hands and feet also occurred in this latter group. No ulcerations or bullae
      formation were seen and changes resolved spontaneously in all patients within 3
      weeks leaving marked hyperpigmentation in involved areas. Renal function declined
      in nine of 10 patients concomitantly with evolving cutaneous changes, but
      recovered in all except one. Cutaneous side effects were more frequent with
      increasing doses of etoposide and carboplatin and in patients with deteriorating
      renal function. Plasma concentrations during high-dose chemotherapy should be
      monitored to avoid excessive serum levels and toxicity, especially in patients at
      risk of renal dysfunction.

PMID- 1362686
TI  - Long-term acyclovir prophylaxis for prevention of varicella zoster virus
      infection after autologous blood stem cell transplantation in patients with acute
      leukemia.
AB  - Twenty-one adult patients with acute leukemia who underwent autologous blood stem
      cell transplantation (ABSCT) and who received acyclovir during the first 6 months
      after transplant to prevent varicella zoster virus (VZV) infection were studied
      retrospectively to determine the incidence and outcome of VZV infection after
      ABSCT. The cumulative risk of VZV infection was 32% by 1 year after transplant.
      No patient developed VZV while on prophylactic acyclovir but five (24%) had
      localized herpes zoster within 1 month of acyclovir withdrawal. There were no
      deaths related to VZV infection and only one patient had disseminated disease and
      post-herpetic neuralgia. These preliminary results suggest that the incidence and
      outcome of VZV infection after ABSCT largely parallel those reported in marrow
      transplant patients and that long-term acyclovir prophylaxis delays but does not
      prevent VZV infection. Prophylaxis of VZV infection after ABSCT requires new
      therapeutic approaches.

PMID- 1362687
TI  - Non-haematological toxicity limiting the application of sequential high dose
      chemotherapy in patients with advanced breast cancer.
AB  - A programme of repeated high dose chemotherapy for advanced breast cancer was
      developed using (1) cyclophosphamide 4 g/m2 followed by autologous peripheral
      blood stem cell (PBSC) collection; (2) three cycles of conventional dose
      chemotherapy; (3) high dose cyclophosphamide, cisplatin, and carmustine with PBSC
      rescue; and (4) high dose etoposide and melphalan with PBSC rescue. Fifteen
      eligible patients had advanced poor prognosis breast cancer either at initial
      diagnosis (one patient) or at relapse (14 patients). During the course of the
      protocol, there were three treatment related deaths, two patient withdrawals due
      to debilitating toxicity, five patient withdrawals due to disease progression,
      and one patient withdrawal due to inadequate collection of PBSC. The remaining
      four patients did not complete the planned protocol as the programme was
      terminated because of the unacceptable morbidity and mortality. They were treated
      with an alternative high dose chemotherapy protocol which was well tolerated.
      This study highlights the significant problems associated with a complex
      sequential high dose chemotherapy regimen. Cyclophosphamide mobilized PBSC
      infused following high dose chemotherapy enables rapid haematological recovery.
      However the non-haematological toxicity following high dose chemotherapy regimens
      is often severe and may limit the application of certain sequential high dose
      chemotherapy combinations in patients with breast cancer.

PMID- 1362688
TI  - A case of affective disorder associated with the misuse of 'anabolic steroids'.
AB  - In the pursuit of gains in muscle size and strength, body-builders may mistakenly
      use illicit drugs believing them to be anabolic steroids. The case described
      illustrates the physical and psychological dangers of such behaviour.

PMID- 1362689
TI  - Differential sensitivities of the sphincter of Oddi and gallbladder to
      cholecystokinin in the guinea pig: their role in transsphincteric bile flow.
AB  - Cholecystokinin (CCK) is considered to simply contract the gallbladder and relax
      the sphincter of Oddi with meals. In this study, we examined this hypothesis by
      investigating the action of CCK on the sphincter of Oddi and gallbladder of the
      guinea pig. The experimental design used an in vitro preparation of the sphincter
      of Oddi to measure contraction of the circular muscle. CCK increased tone in both
      the gallbladder and the sphincter of Oddi in a concentration-dependent manner.
      The normalized concentration-response curves for CCK, however, revealed that the
      gallbladder had a greater sensitivity to CCK (ED50 7 nM) than the sphincter of
      Oddi (ED50 22 nM; p < 0.01). Conversely, the sphincter was more sensitive to
      bethanechol than was the gallbladder. When the sphincter of Oddi was stimulated
      maximally with CCK in the presence of atropine (10(-6) M) or tetrodotoxin (10(-6)
      M), the contractile response was significantly reduced (p < 0.05) although not
      abolished. Conversely, atropine completely abolished the responses to bethanechol
      (10(-3) M) and transmural field stimulation (70 V, 10 Hz, 1 ms, for 20 s).
      Transmural field stimulation of the sphincter that had been precontracted with
      CCK (26 nM) caused a transient, initial relaxation followed by contraction.
      Pretreatment with atropine augmented the duration of this relaxation, which could
      be completely abolished by tetrodotoxin. Thus, CCK contracts the sphincter of
      Oddi in the guinea pig by a direct (myogenic) and a neural (likely cholinergic)
      mechanism. Relaxation of the sphincter of Oddi also occurs in the guinea pig via
      noncholinergic inhibitory nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362690
TI  - Impact of enalapril therapy on in vitro coronary artery responsiveness in pacing
      induced heart failure.
AB  - In vitro coronary artery responsiveness to angiotensin I, angiotensin II,
      noradrenaline, phenylephrine, BHT 920, and potassium chloride together with
      functional relaxation to acetylcholine was investigated in dogs with pacing
      induced heart failure treated with enalapril (oral administration of 10 mg.day-1)
      for a mean duration of 26 days. Although maximal responses generated to both
      angiotensin I and angiotensin II were unaltered in the enalapril-treated group,
      angiotensin II became more potent following enalapril treatment: the EC50 for
      angiotensin II following placebo treatment was 2.4 (0.6-5.8; 95% confidence
      limits) nM and following enalapril treatment was 0.03 (0.007-0.1; 95% confidence
      limits) nM. In addition to the above changes, coronary artery rings from dogs
      treated with enalapril developed significantly less tension to noradrenaline,
      phenylephrine, and BHT 920. In contrast, responses to potassium chloride were
      unaltered following enalapril treatment. However, the relaxation to acetylcholine
      was enhanced from 38.9 +/- 3.0 to 50.4 +/- 3.5% (placebo versus enalapril, p <
      0.05). These findings indicate that enalapril may possess alpha-blocking
      properties and enhance the relaxation response to acetylcholine through an
      endothelial-dependent mechanism in addition to inhibiting converting enzyme.

PMID- 1362691
TI  - Decrease in hypothalamic vasopressin mRNA poly(A) tail length following
      physiological stimulation.
AB  - 1. The vasopressin mRNA in the adult male rat hypothalamus is modulated in two
      distinct ways by a dehydration stimulus. In addition to the well-established
      increase in transcript abundance, it has recently been demonstrated that the
      vasopressin mRNA poly(A) tail increases in length. 2. We have studied the
      ontogeny of poly(A) tail length modulation in neonates in response to milk
      deprivation and found that poly(A) tail length changes are age dependent. In
      neonates older than 12 days of age, the vasopressin mRNA poly(A) tail length
      increased with milk deprivation and this effect became more marked in older
      animals. However, in rats 5 to 9 days old, milk deprivation resulted in a
      detectable though not significant decrease in vasopressin mRNA poly(A) tail
      length. 3. As milk deprivation is a combination of dehydration and starvation, we
      investigated the effect of the latter stimulus in more mature animals. We found
      that starvation modifies the length of the vasopressin mRNA poly(A) tail in a
      manner opposite that due to dehydration. 4. Our data indicate a novel mode of
      regulation of the vasopressin mRNA, namely, poly(A) tail shortening. This system
      provides a model for future studies concerning the adaptive role of poly(A) tail
      length modulation in response to physiological stimuli.

PMID- 1362694
TI  - Selected papers from the Jerusalem 9th International Symposium on
      Atherosclerosis. Rosemont, Illinois, October 6-11, 1991.

PMID- 1362693
TI  - [Histologic evaluation of potential new beta-adrenolytics].
AB  - The present paper investigated histological changes in the myocardium in two
      potential beta-adrenolytic agents, 4-[3-isopropylamino-2-hydroxypropoxy]-3
      [propoxymethyl]acetophenone and 4-[3-isopropylamino-hydroxypropoxy]-3
      [pentyloxymethyl]acetophenon e after intravenous administration in doses of 8
      mg/kg and 24 mg/kg. It results from the found data that in both agents in the
      doses used there are no necrotic changes in the myocardium and the values of the
      impairment range within the 1st degree of Zbinden's classification, comparable to
      the standard metipranolol.

PMID- 1362692
TI  - Differential expression of tyrosine hydroxylase mRNA in the developing rat
      mesencephalon.
AB  - 1. With respect to the mesostriatal projection, the mesencephalon is composed of
      two dopaminergic (DA) cell populations, called dorsal tier and ventral tier.
      Strong evidence suggests differences in both the spatial and the temporal
      sequence of the innervation of the striatum between the two groups, with the
      ventral tier neurons innervating striatal patches prenatally and dorsal tier
      cells innervating striatal matrix postnatally. 2. Using in situ hybridization, we
      have examined the expression of the gene coding for tyrosine hydroxylase (TH) in
      mesencephalic DA neurons with respect to their postnatal development. Two
      ontogenic patterns of expression were observed: (a) dorsal tier neurons of the
      medial mesencephalon exhibited a sharp increase in expression beginning after
      birth, peaking on day 14, then decreasing and, finally, stabilizing; and (b)
      ventral tier neurons and dorsal tier cells from the lateral and the medial-dorsal
      mesencephalon showed only a slight increase in TH mRNA, reaching a plateau at
      P10. 3. The time course of the observed increase in TH gene expression in the
      first group, generally parallels the innervation of their target cells in the
      striatal matrix, suggesting that TH gene expression in these cells may be
      influenced by their postsynaptic cells or by the innervation process.

PMID- 1362696
TI  - Aggressive cancer pain management--where does the buck stop?
AB  - A comprehensive cancer pain management consultative service sponsored by a
      department of anesthesia at a moderately sized community hospital is described.
      Medical records of 111 patients from 1986 to 1990 were reviewed. Different
      therapies utilized and patient populations are described. It is suggested that
      trained anesthesiologists who are committed to a multidisciplinary approach to
      alleviating cancer pain can provide similar support.

PMID- 1362695
TI  - Lipid parameters and apolipoprotein B RFLP studies: comparison of normal and
      coronary heart disease groups as defined by angiography.
AB  - We have compared the lipid and apolipoprotein values and the frequency of DNA
      polymorphisms of the apolipoprotein B gene detected with the restriction enzymes,
      Xba I and Eco RI in 122 patients with coronary heart disease (CHD) and 80 control
      subjects. The patients with coronary heart disease (CHD) were defined by > 70%
      stenosis in at least one major coronary artery whereas the controls showed no
      signs of coronary artery narrowing at angiography. When males and females were
      considered separately, differences in triglyceride, total cholesterol and high
      density lipoprotein-cholesterol (HDL-cholesterol) between CHD and control
      subjects were significant only for females. The polymorphism studies showed no
      significant differences between the control and CHD subjects except for a
      difference in the frequency in the females of the Xba I polymorphism (p < 0.05).
      The X1 allele (absence of the restriction enzyme cutting site) occurred
      significantly more often in the patient group than in the controls. Individuals
      with the X1X2 genotype had the highest serum total cholesterol whereas those with
      the X1X1 genotype had the lowest HDL-cholesterol value. Generally, the
      associations between the Xba I and Eco RI alleles and serum lipid levels were
      weak and inconsistent. Furthermore, even after careful selection of disease and
      control groups, a useful role for restriction fragment length polymorphism
      studies in assessing CHD risk in individual patients was not demonstrated.

PMID- 1362697
TI  - Mechanisms in B-Cell Neoplasia 1992. Workshop. Bethesda, Maryland, April 21-23,
      1992.

PMID- 1362700
TI  - Aluminum in Biology and Medicine. Symposium proceedings. London, 19-21 November
      1991.

PMID- 1362699
TI  - p53 mutations in B-cell chronic lymphocytic leukemia.

PMID- 1362698
TI  - Multidrug resistance of a continuously differentiating monoclonal B lineage in
      the blood and bone marrow of patients with multiple myeloma.

PMID- 1362701
TI  - Prompt diagnosis of 'acute groin' conditions in infants.
AB  - Urgent sonographic examination of the groin was performed in 58 patients under
      the age of two years. Accurate diagnosis was done in conditions such as:
      incarcerated inguinal hernia, twisted undescended testis, incarcerated ovary in
      inguinal hernia and others. Ultrasonography facilitated decision-making and
      differentiation between surgical and non-surgical conditions.

PMID- 1362702
TI  - Stereoselective binding of tertatolol and of 4-hydroxytertatolol to human plasma
      proteins.
AB  - The binding of racemic tertatolol and 4-hydroxytertatolol and of their
      enantiomers was compared in alpha 1-acid glycoprotein and albumin solutions. The
      binding rate of S(-)tertatolol to alpha 1-acid glycoprotein was much greater than
      that of R(+)tertatolol, the binding of the racemate being intermediate. It was
      the reverse for the binding to albumin, although the differences were slight. The
      binding of 4-hydroxytertatolol racemate and enantiomers was very low as compared
      to the binding of tertatolol, and there were no statistically significant
      differences in the binding of the 4-hydroxytertatolol enantiomers to either alpha
      1-acid glycoprotein or albumin.

PMID- 1362703
TI  - Changes on distribution of CD4+/CD45RA- and CD8+/CD11- cells in tumor
      infiltrating lymphocytes of renal cell carcinoma associated with tumor
      progression.
AB  - To study the distribution of subsets of T cells in renal cell carcinoma,
      peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) were
      analyzed in 43 untreated patients using two-color flow cytometry. An increase in
      the relative number of CD4+/CD45RA-, CD8+/CD11- and HLA-DR+/CD3+ cells was shown
      in TIL when compared with PBL. When the influence of various tumor factors on
      subsets of TIL was examined, a decrease in CD4, CD4+/CD45RA- and CD16+/CD57-
      cells and an increase in CD8+ and CD8+/CD11- cells was observed along with the
      aggravation of tumor stage and grade. In TIL of stage III/IV and grade III/IV
      disease, most patients showed an increase in CD8+/CD11- associated with a
      decrease in CD4+/CD45RA- cells, or the reverse, resulting in changes of the
      CD4+/CD45RA- to CD8+/CD11- ratio. The prognosis for these patients was poor,
      suggesting that changes in the ratio were a sign of the impairment of local
      immune status associated with disease progression.

PMID- 1362704
TI  - A-77636: a potent and selective dopamine D1 receptor agonist with
      antiparkinsonian activity in marmosets.
AB  - A-77636, ((1R,3S) 3-(1'-adamantyl)-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1H-2
      benz opyran hydrochloride), is a selective dopamine D1 receptor agonist. In a
      battery of receptor binding assays, A-77636 shows the highest affinity (pKi =
      7.40 +/- 0.09; Ki = 39.8 nM) for the dopamine D1 receptor. A-77636 is an agonist
      at the dopamine D1 receptors in the fish retina (pEC50 = 8.13; EC50 = 1.1 nM;
      intrinsic activity = 102% of dopamine) and the rat caudate-putamen (pEC50 = 8.97;
      intrinsic activity = 134% of dopamine). The compound is functionally inactive at
      dopamine D2 receptors (EC50 > 10 microM). In rats with unilateral 6-OHDA (6
      hydroxydopamine) lesions of the nigro-striatal dopaminergic pathway, A-77636
      elicits prolonged (> 20 h) contralateral turning that is blocked by SCH 23390, a
      D1 receptor antagonist, but not by haloperidol at doses selective for the
      dopamine D2 receptor. Higher doses of A-77636 produce forelimb clonus in rats and
      mice. When tested in marmosets treated with MPTP to induce a parkinsonian-like
      state, A-77636 increases locomotor activity and decreases the severity of the
      parkinsonian-like symptoms: the compound is active after either subcutaneous or
      oral administration. A-77641, the optical antipode of A-77636, has a lower
      affinity towards the dopamine D1 receptor (pKi = 5.14, Ki = 7200 nM), is less
      potent as a dopamine D1 receptor agonist (pEC50 = 5.65; EC50 = 2200 nM), fails to
      elicit turning in the 6-OHDA-lesioned rat, and lacks antiparkinsonian efficacy in
      the MPTP-treated marmoset.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362705
TI  - Sensitization, response fluctuation and long-term effect of SKF-82958 and
      bromocriptine in the hemi-parkinsonian rat.
AB  - Rats with a unilateral 6-hydroxydopamine lesion of substantia nigra were treated
      with the dopamine agonists SKF-82958 (D1 receptor selective) or bromocriptine (D2
      receptor-selective) and their circling response recorded. Both of the compounds
      induced an acute episode of rotation directed away from the lesioned side.
      Consecutive daily treatments with either compound usually resulted in a
      significantly increased average response (sensitization) over a 3- to 6-day
      treatment period. But nearly all animals treated with low doses of either SKF
      82958 or bromocriptine exhibited one or more days when they were totally
      unresponsive to drug treatment. Response fluctuations thus were not exclusively
      associated with D1 or D2 receptor agonist treatment. When subsequently tested,
      undrugged, in the drug-associated environment, 2, 4 and 10 weeks after their last
      drug treatment, rats that had previously been treated with SKF-82958 exhibited
      rapid contralateral rotation while rats that had previously been treated with
      bromocriptine showed no such undrugged rotation. This result is consistent with
      previous findings that the D1 receptor agonist, SKF-38393, but not the D2
      receptor agonist, quinpirole, had long-term behavioral effect in nigral rats, and
      suggests that persistent motor consequences of limited treatment with dopamine
      receptor agonists are D1 receptor-related.

PMID- 1362706
TI  - Central alpha-adrenoceptor subtypes involved in the emetic pathway in cats.
AB  - The intracerebroventricular (i.c.v.) injection of clonidine, xylazine, adrenaline
      and methoxamine elicited dose-dependent vomiting in cats in that order of
      potency. The vomiting induced by clonidine, xylazine and adrenaline was
      antagonized by i.c.v. yohimbine and phentolamine possessing alpha 2-adrenoceptor
      blocking activity, but not by prazosin showing alpha 1-adrenoceptor-blocking
      activity. In contrast, methoxamine-induced vomiting was antagonized by prazosin,
      but not by yohimbine. The vomiting induced by xylazine and adrenaline was not
      prevented by i.c.v. 6-hydroxydopamine treatment, but was prevented by i.c.v.
      reserpine treatment. Ablation of the area postrema with some damage to extremely
      adjacent areas abolished the vomiting induced by each alpha-adrenoceptor agonist.
      These results indicate that both central alpha 1- and alpha 2-adrenoceptors are
      involved in the emetic pathway in cats, although alpha 2-adrenoceptors seem to
      have the main role. It is also suggested that monoamines, and in particular 5
      hydroxytryptamine in the brain, are involved in the regulation of alpha
      adrenoceptor-mediated vomiting.

PMID- 1362707
TI  - Cocaine releases limbic acetylcholine through endogenous dopamine action on D1
      receptors.
AB  - Cocaine (10 and 20 mg/kg i.p.) enhanced the extracellular concentration of
      acetylcholine (ACh) in the ventral striatum of freely moving rats. The
      enhancement was prevented both by dopamine (DA) D1 receptor blockade with SCH
      23390 (0.1 mg/kg s.c.) and by depletion of endogenous DA after coadministration
      of reserpine (5 mg/kg i.p.) and alpha-methyltyrosine (alpha-MT) (150 mg/kg i.p.).
      In contrast, blockade of DA D2 receptors with (-)-sulpiride (20 mg/kg i.p.) did
      not prevent the cocaine-induced increase in ACh release. These results indicate
      that the cocaine-induced stimulation of ACh release is mediated by an action of
      DA on D1 receptors, and suggest that the enhancement of ACh release might play a
      functional role in the central effects of cocaine. Moreover, DA depletion after
      reserpine + alpha-MT or D1 receptor blockade with SCH 23390 led to a comparable
      decrease of baseline ACh release, suggesting that striatal cholinergic
      interneurons are under D1 receptor-mediated facilitatory dopaminergic control.

PMID- 1362709
TI  - Establishment of three categories of P-fimbriated Escherichia coli strains that
      show different toxic phenotypes and belong to particular O serogroups.
AB  - Eight hundred and nineteen strains of Escherichia coli isolated in Spain between
      1986 and 1991 from extraintestinal infections and feces of healthy controls were
      investigated for expression of P-fimbriae using a particle agglutination test.
      Among strains causing urinary tract infections, sepsis and other extraintestinal
      infections, P-fimbriae were found in 31% (130/420) (P < 0.001), 25% (30/118) (P <
      0.001) and 12% (11/92) (P < 0.5) respectively. In contrast, only 7% (14/189) of
      faecal isolates from healthy individuals carried P-fimbriae. According to two
      more common toxic markers detected in this study (alpha-haemolysin and cytotoxic
      necrotizing factor type 1), P-fimbriated E. coli strains were grouped into three
      categories: haemolysin+cytotoxic necrosing factor+ (Hly+CNF1+) (68/185; 37%),
      haemolysin+cytotoxic necrosing factor- (Hly+CNF1-) (61/185; 33%) and Hly-CNF1-
      (56/185; 30%). The 185 P-fimbriated strains belonged to 17 different O
      serogroups. However, 148 (80%) were of one of six serogroups (O1, O2, O4, O6, O7
      and O18). The most frequent serogroups determined in the Hly+CNF1+ strains were
      the O4 and O6 (53/68; 78%), in the Hly+CNF1- strains it was the O18 (27/61; 44%)
      and in the Hly-CNF1- strains the O1, O2 and O7 (41/56; 73%). The majority
      (160/185; 86%) of P-fimbriated E. coli expressed the mannose-resistant
      haemagglutinin type IVa.

PMID- 1362708
TI  - Thermal regulation of fimA, the Escherichia coli gene coding for the type 1
      fimbrial subunit protein.
AB  - The effect of temperature on expression of fimA, the gene coding for the phase
      variable type 1 fimbrial subunit protein of Escherichia coli K-12 was
      investigated. In a genetic background in which the orientation of the DNA
      fragment carrying the fimA promoter was determined by the activity of the
      'orientationally unbiased' FimB recombinase, fimA transcription was consistently
      higher at 30 degrees C than at 37 degrees C. This apparent increase in fimA
      expression was found to be due to the fact that the fimA site-specific
      recombination system had become directionally biased at the lower temperature
      such that the bacterial population contained more cells in the ON phase than at
      37 degrees C. When expression of fimA was studied in a strain genetically
      incapable of switching the fimA promoter to the OFF phase (i.e. all cells in the
      culture were phase-locked ON), fimA transcription was found to be higher at 37
      degrees C than at 30 degrees C. Thus, transcription from the fimA promoter was
      subject to temperature control and the site-specific recombination system
      determining the orientation of the promoter DNA fragment was temperature
      modulated. Furthermore, it was found that the thermosensitive fimA promoter was
      subject to transcriptional silencing by the HNS nucleoid protein, in a manner
      analogous to that described for other thermoregulated adhesins.

PMID- 1362710
TI  - Satellite III DNA: regions of extreme endonuclease resistance and inter
      individual polymorphism in the Mb size range.
AB  - Southern analysis of within-gel digested and restricted human cells has revealed
      very large Satellite III restriction fragments which show clear inter-individual
      length polymorphism. The Mb and sub-Mb length of these fragments indicate that
      they arise from regions of heterochromatin which contain homogeneous Satellite
      III sequences of peculiar resistance to common endonucleases. Based on sequence
      alone, such regions would be little digested by endonuclease digestion of
      chromatin in metaphase, regardless of its method of preparation. Polymorphic
      regions such as these might be expected to stain as part of the C-banding seen in
      endonuclease treated metaphase chromosomes, and may in part account for inter
      individual C-band heteromorphisms.

PMID- 1362711
TI  - The effects of (+/-)-idazoxan and its stereoisomers on mouse vas deferens
      motility in vitro. A comparison with yohimbine.
AB  - The effects of idazoxan (IDZ) and its stereoisomers were compared to that of a
      classical alpha 2-antagonist, yohimbine (YOH), on para-aminoclonidine (PAC)- and
      norepinephrine (NE)-mediated inhibition of the twitch response evoked in the
      mouse vas deferens by low-frequency (0.1 Hz) field stimulation. (+/-)-IDZ and (+)
      IDZ antagonized the inhibitory effects of PAC, (+)-IDZ being twice as potent as
      (+/-)-IDZ; in contrast, antagonism by (-)-IDZ failed to meet Schild criteria for
      a competitive mechanism. YOH completely reversed the inhibition of twitch
      response induced by NE, but not that induced by PAC; in the latter case, residual
      inhibition was almost fully reversed by (+)-IDZ and to a lesser extent by (+/-)
      IDZ, while (-)-IDZ proved ineffective. These results provide pharmacological
      evidence of alpha 2-receptor heterogeneity at the vas deferens level. A possible
      additional mechanism involving imidazoline binding sites is discussed.

PMID- 1362712
TI  - Detection of thyroid-stimulating antibody in patients with inflammatory
      thyrotoxicosis.
AB  - The detection of thyrotropin-binding inhibitory immunoglobulins (TBII) and/or
      thyroid-stimulating antibody (TSAb) has been reported in some patients with
      painless thyroiditis (PT) or subacute thyroiditis (SAT). However, its mechanism
      is unknown. TBII and TSAb measured using cultured FRTL-5 thyroid cells were
      evaluated in 18 patients with PT, 11 patients with SAT and a patient with SAT
      like symptoms. In PT, we detected both TBII and TSAb activities in only 1
      patient. This case had first come to our attention with subclinical
      hypothyroidism and had already had weakly positive TSAb activity (205.9%) 1 year
      before the present onset of PT. This patient had a transient thyrotoxicosis with
      a low uptake (24 h) of 123I (4.3%) and 821.0% TSAb activity, and subsequently
      developed a transient subclinical hypothyroidism. Even after 2 years, she still
      had positive TSAb activity (382.3%). In SAT, TBII and TSAb activities were not
      detected during the courses of any patients. A patient with transient
      thyrotoxicosis, who had a high uptake (30 min) of 99mTc (5.6%) and SAT-like
      symptoms (painful tenderness on right thyroid lobe and markedly accelerated
      erythrocyte sedimentation rate), showed positive activities of TBII (34.9%) and
      TSAb activity (1,366.9%). Histological findings by thyroid needle biopsy
      performed in the thyrotoxic phase showed coexistence of granulomatous
      inflammatory changes and hyperplasia with papillary folds of some residual
      follicular cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362713
TI  - Accelerated rejection of allografted rat liver perfused with anti-ICAM-1
      monoclonal antibody.
AB  - Infusion of mouse anti-rat ICAM-1 into the portal vein of ACI rat liver graft
      before transplantation resulted in accelerated rejection by LEW recipients (2.9
      +/- 2.5 days), when compared to the ACI liver grafts perfused with either Lactate
      Ringer's solution (9.8 +/- 1.3) or anti-human ICAM-1 mAb (9.8 +/- 3.1).
      Histologic features of anti-rat ICAM-1 perfused grafts were spotty ischemic
      necrosis, whereas those of control grafts were marked cellular infiltration.
      These combined survival and histologic data suggest that the accelerated
      rejection may be mediated by vascular deterioration.

PMID- 1362714
TI  - Interferon-gamma-mediated suppression of erythroid progenitor growth by a HLA-DR-
      and CD4-positive subset of T lymphocytes in acute myeloid leukemia.
AB  - In this study, we examined the effects of peripheral blood T lymphocytes from
      patients with acute myeloid leukemia (AML) on marrow-derived erythroid
      progenitors (BFU-DE and CFU-DE) growth in an in vivo culture by using the plasma
      clot diffusion chamber (DC) technique. The application of double-compartment
      chambers (each compartment separated by a membrane filter) makes the
      investigations of humoral effects of T lymphocytes upon marrow erythroid
      progenitors proliferation possible. T lymphocytes of AML-patients in the absence
      of a statistically significant number of monocytes suppressed the growth of BFU
      DE and CFU-DE from T lymphocyte- and adherent cell-depleted marrows. The
      inhibition ability was restricted to the CD4-positive enriched fraction obtained
      from T cells by using the negative selection technique. In contrast, the CD8
      positive enriched fraction had no effect on erythroid colony formation.
      Autologous and allogeneic BFU-DE and CFU-DE were similarly affected by the CD4
      positive T cells. Treatment of T cells with monoclonal antibodies against HLA-DR
      before cocultures, completely abrogated the suppression of BFU-DE and CFU-DE
      derived colony formation. Suppressive activity detected in the CD4-positive T
      cells was also totally abolished by treatment with anti-interferon-gamma
      antibodies; whereas the inhibition was retained after 30 Gy radiation. Under
      these experimental conditions, resting T lymphocytes from healthy subjects did
      not affect the erythroid colony formation. Our data show that in AML-patients, a
      circulating HLA-DR-positive, less radiosensitive subset within the CD4-positive T
      cells is capable of inducing an interferon-gamma-mediated suppression of
      erythropoiesis, at least in DC culture.

PMID- 1362715
TI  - Proceedings of the 2nd International Symposium on Clinical Evaluation of Drug
      Efficacy in Urinary Tract Infection. International consensus discussion. Berlin,
      Germany, 28-29 June 1991.

PMID- 1362716
TI  - Effects of histamine on pulmonary artery system in humans after pretreatment with
      an H2-receptor-antagonist.

PMID- 1362717
TI  - Drug interaction involving P-glycoprotein in relation to multidrug resistance.

PMID- 1362718
TI  - Failure to control AIDS-related CMV-retinitis with intravenous ganciclovir.
AB  - Between January 1988 and May 1991 intravenous ganciclovir (GCV) treatment was
      administered to eight male AIDS-patients with unilateral cytomegalovirus (CMV)
      retinitis. Despite of continuous therapy with at least the recommended dose of
      GCV, three patients developed slowly progressive CMV-retinitis in the fellow eye
      after 4 to 13 months. The progression could not be stopped by GCV and thus
      bilateral blindness resulted after 12 to 22 months. The number of CD4-lymphocytes
      in the blood was reduced in all patients, but particularly in patients with
      progressive disease. Treatment failure was partly related to the duration of CMV
      retinitis and partly to the degree of immunodeficiency. Intravenous treatment
      with GCV alone can not stop the progression of CMV-retinitis in long-term
      survivors and in those with advanced immunodeficiency.

PMID- 1362719
TI  - The first normal oral mucosa epithelium in which gamma-glutamyl transpeptidase
      activity has been detected.
AB  - A portion of consistently gamma-glutamyl transpeptidase-positive epithelium in
      the normal oral mucosa of rats is described. This is the first normal oral mucosa
      epithelium reported to express activity of the transpeptidase. This enzyme has
      been used as a marker of malignant transformation in tissues such as epidermis
      and oral mucosa epithelium. Complementary studies of the enzyme-positive portion
      of oral mucosa and a neighbouring negative portion, suggest that, in this model,
      expression of gamma-glutamyl transpeptidase is linked to a terminally
      differentiated epithelium.

PMID- 1362720
TI  - Pneumocandins from Zalerion arboricola. V. Glutamic acid- and leucine-derived
      amino acids in pneumocandin A0 (L-671,329) and distinct origins of the
      substituted proline residues in pneumocandins A0 and B0.

PMID- 1362721
TI  - The structure of pyrizinostatin.

PMID- 1362722
TI  - The efferent modulation of mammalian inner hair cell afferents.
AB  - The results of immunocytochemical, enzymatic and electrophysiological studies
      have indicated that acetylcholine and GABA may act as neurotransmitters in
      lateral olivocochlear efferent endings on inner hair cell afferent dendrites.
      Since spike activity can be recorded in the dendritic region of inner hair cells,
      microiontophoretic techniques were used testing the possible neurotransmitter
      candidates, acetylcholine and GABA, on spontaneous and induced firing of the
      afferent dendrites. The experiments were carried out in anaesthetised guinea
      pigs, the third and fourth turns of the cochlea being exposed for electrode
      penetration. Ejection of acetylcholine resulted in a pronounced dose-dependent
      increase in subsynaptic spiking activity. Furthermore, acetylcholine enhanced
      glutamate-induced activity. In contrast, even at high doses, GABA had very little
      effect on the spontaneous cochlear firing rate. When the firing rate had first
      been enhanced by glutamate or N-methyl-D-aspartate, however, this activation
      could be reduced by the ejection of GABA. A similar reduction was observed when
      the firing rate had been enhanced with acetylcholine. The results of our studies
      support the hypothesis that these substances are involved in efferent
      neurotransmission on inner hair cell afferent fibres. It should be pointed out,
      however, that besides acetylcholine and GABA, several opioids such as enkephalins
      and dynorphins seem to be involved in efferent cochlear innervation.

PMID- 1362723
TI  - N omega-nitro-L-arginine influences cerebral metabolism in awake sheep.
AB  - Cerebral vasodilation in hypoxia may involve endothelium-derived relaxing factor
      nitric oxide (NO). An inhibitor of NO formation, N omega-nitro-L-arginine (LNA,
      100 micrograms/kg i.v.), was given to conscious sheep (n = 6) during normoxia and
      again in hypocapnic hypoxia (arterial PO2 approximately 38 Torr). Blood samples
      were obtained from the aorta and sagittal sinus, and cerebral blood flow (CBF)
      was measured with 15-microns radiolabeled microspheres. During normoxia, LNA
      elevated (P < 0.05) mean arterial pressure from 82 +/- 3 to 88 +/- 2 (SE) mmHg
      and cerebral perfusion pressure (CPP) from 72 +/- 3 to 79 +/- 3 mmHg, CBF was
      unchanged, and cerebral lactate release (CLR) rose temporarily from 0.0 +/- 1.9
      to 13.3 +/- 8.7 mumol.min-1 x 100 g-1 (P < 0.05). The glucose-O2 index declined
      (P < 0.05) from 1.67 +/- 0.16 to 1.03 +/- 0.4 mumol.min-1 x 100 g-1. Hypoxia
      increased CBF from 59.9 +/- 5.4 to 122.5 +/- 17.5 ml.min-1 x 100 g-1 and the
      glucose-O2 index from 1.75 +/- 0.43 to 2.49 +/- 0.52 mumol.min-1 x 100 g-1 and
      decreased brain CO2 output, brain respiratory quotient, and CPP (all P < 0.05),
      while cerebral O2 uptake, CLR, and CPP were unchanged. LNA given during hypoxia
      decreased CBF to 77.7 +/- 11.8 ml.min-1 x 100 g-1 and cerebral O2 uptake from 154
      +/- 22 to 105.2 +/- 12.4 mumol.min-1 x 100 g-1 and further elevated mean arterial
      pressure to 98 +/- 2 mmHg (all P < 0.05), CLR was unchanged, and, surprisingly,
      brain CO2 output and respiratory quotient were reduced dramatically to negative
      values (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362724
TI  - Inhibitory NANC nerves in human tracheal smooth muscle: a quest for the
      neurotransmitter.
AB  - Inhibitory nonadrenergic noncholinergic (i-NANC) nerves are the only neural
      bronchodilator pathway in human airways. Possible candidates for the
      neurotransmitter include vasoactive intestinal peptide (VIP) and nitric oxide
      (NO) and purines such as ATP. We have investigated the potential role of these
      neurotransmitters. Phosphoramidon (10(-5) M) significantly potentiated
      relaxations to low doses of VIP with no effect on i-NANC responses. Relaxations
      induced by VIp were abolished with alpha-chymotrypsin (2 U/ml), but i-NANC
      responses were unaffected. Reactive blue 2 had no effect on i-NANC neural
      responses, indicating that endogenous ATP was not involved. The NO synthase
      inhibitor L-NG-nitroarginine methyl ester (L-NAME, 10(-4) M) produced a
      concentration-dependent inhibition of the i-NANC response, producing almost
      complete inhibition at every frequency studied (0.5-40 Hz), whereas L-NG
      monomethyl arginine was effective only at low stimulation frequencies. The
      inhibitory effect of L-NAME was partially reversed by L- but not D-arginine, and
      D-NAME was without effect. These results suggest that in human tracheal segments
      the neural bronchodilator response is mediated by NO, and there is no functional
      evidence for implicating VIP in this response.

PMID- 1362725
TI  - Histamine decreases left ventricular contractility in normal human subjects.
AB  - To determine whether histamine alters human left ventricular contractility we
      measured heart rate, calibrated carotid arterial pressure, and left ventricular
      dimensions (echocardiogram) in nine healthy volunteers. We assessed baseline
      contractility using the end-systolic pressure-dimension relationship and the end
      systolic meridional wall stress-rate-corrected velocity of circumferential fiber
      shortening relationship determined over a wide range of afterloads using
      phenylephrine and nitroprusside infusions. We then infused histamine for 3-5 min
      at a dose predetermined to decrease mean arterial pressure by 20%, both before
      and after H1 receptor antagonist pretreatment (diphenhydramine 50 mg i.v.).
      Histamine decreased end-systolic pressure but, unlike an equally hypotensive
      infusion of nitroprusside, did not decrease end-systolic dimension or increase
      fractional shortening. Histamine also decreased velocity of circumferential fiber
      shortening at the same end-systolic meridional wall stress as controls (P <
      0.05). These effects of histamine were inhibited by H1 antagonist pretreatment.
      We conclude that the dominant effect of histamine on the human heart is to
      decrease left ventricular contractility and that this decrease in contractility
      is dependent, at least partially, on H1-receptor activation.

PMID- 1362726
TI  - Brain glutamate metabolism during metabolic alkalosis and acidosis.
AB  - Glutamate modifies ventilation by altering neural excitability centrally.
      Metabolic acid-base perturbations may also alter cerebral glutamate metabolism
      locally and thus affect ventilation. Therefore, the effect of metabolic acid-base
      perturbations on central nervous system glutamate metabolism was studied in
      pentobarbital-anesthetized dogs under normal acid-base conditions and during
      isocapnic metabolic alkalosis and acidosis. Cerebrospinal fluid transfer rates of
      radiotracer [13N]ammonia and of [13N]glutamine synthesized de novo via the
      reaction glutamate+NH3-->glutamine in brain glia were measured during normal acid
      base conditions and after 90 min of acute isocapnic metabolic alkalosis and
      acidosis. Cerebrospinal fluid [13N]ammonia and [13N]glutamine transfer rates
      decreased in metabolic acidosis. Maximal glial glutamine efflux rate jm equals
      85.6 +/- 9.5 (SE) mumol.l-1 x min-1 in all animals. No difference in jm was
      observed in metabolic alkalosis or acidosis. Mean cerebral cortical glutamate
      concentration was significantly lower in acidosis [7.01 +/- 0.45 (SE) mumol/g
      brain tissue] and tended to be larger in alkalosis, compared with 7.97 +/- 0.89
      mumol/g in normal acid-base conditions. There was a similar change in cerebral
      cortical gamma-aminobutyric acid concentration. Within the limits of the present
      method and measurements, the results suggest that acute metabolic acidosis but
      not alkalosis reduces glial glutamine efflux, corresponding to changes in
      cerebral cortical glutamate metabolism. These results suggest that glutamatergic
      mechanisms may contribute to central respiratory control in metabolic acidosis.

PMID- 1362727
TI  - The kinetics and temporal expression of T-cell activation-associated antigens
      CD15 (LeuM1), CD30 (Ki-1), EMA, and CD11c (LeuM5) by benign activated T cells.
AB  - Cell surface antigens, including CD71 (T9), CD38 (T10), HLA-DR, CD25 (IL2-R),
      CD15 (LeuM1), CD30 (Ki-1), epithelial membrane antigen (EMA), and CD11c (LeuM5),
      have been identified on the surface of neoplastic T-cells. The significance of
      this expression is unknown since the expression of these antigens by benign T
      cells has not been fully investigated. In this study the kinetics, temporal
      relation and hierarchy of expression of these eight cell surface antigens by
      purified normal peripheral blood T cells following activation with
      phytohemagglutinin (PHA) were investigated using one- and two-color flow
      cytometry. All eight antigens were expressed in a hierarchical manner following
      activation of normal peripheral blood T cells with PHA. The sequence of antigen
      expression and the initial time point of this expression was: CD38, < 24 h; CD71,
      CD25, 24 h; EMA, HLA-DR, CD15, 48-72 h; CD30, 72 h; and CD11c, 96-120 h. The
      maximum percentage of T cells expressing each antigen and the time point of
      maximum expression was: CD38 96% at 14 and 17 days; CD71 88%, CD25 94%, EMA 55%,
      and CD30 31% at 96 h; CD15 56% at 120 h; HLA-DR 30% at 168 h; and CD11c 42% at
      240 h. The expression of these 8 antigens clustered into six distinct
      immunophenotypic constellations: Group I: None; Group II: CD38 with CD71 and/or
      CD25; Group III: CD38, CD71, CD25 with HLA-DR, CD15 and/or EMA; Group IV: CD38,
      CD71, CD25, EMA, HLA-DR with CD15, CD30 and/or CD11c; Group V: CD38, CD25, CD11c
      with CD71, EMA and/or HLA-DR; Group VI: CD38 with CD25 and/or CD11c. Finally, EMA
      and CD11c were preferentially expressed by CD4 and CD8 T cells, respectively. In
      summary, these results demonstrate that all eight antigens (1) are associated
      with T-cell activation, (2) are expressed in a hierarchical manner following
      activation, and (3) that this expression clusters into distinct immunophenotypic
      constellations.

PMID- 1362728
TI  - Minor BCR (m-bcr) rearrangements may appear in major BCR (M-bcr)-positive CML
      cases.
AB  - The chromosome 22 derivative, the Philadelphia (Ph) chromosome, results from the
      reciprocal translocation t(9;22) (q34;q11). On DNA level a BCR/ABL rearrangement
      involving the so-called major BCR (Mbcr) from chromosome 22 has been associated
      with chronic myeloid leukemia (CML). For Ph+ ALL a site of rearrangements in the
      5' part of the BCR (breakpoint cluster region) gene on chromosome 22, the so
      called minor bcr region (mbcr) has been described within the first intron in a
      10.8 kb region (=bcr2 or m-BCR1). The BB1 probe detects two Eco fragments of 8.5
      and/or 11 kb, which may appear as monomorphic or heteromorphic alleles, both
      covering bcr2. We have analyzed EcoRI restriction polymorphisms within bcr2 in 42
      patients with a rearrangement in M-bcr (including 39 Philadelphia chromosome
      positive (Ph+) CML patients and 3 ALLs) and in 18 healthy unrelated volunteers.
      Of the 42 patients tested, 52.4% (22) had the 8.5 kb bcr2 allele, 21.4% (9) had
      the 11 kb bcr2 allele, and 26.2% (11) had both the 8.5 and the 11 kb allele. In
      addition to normal allelic polymorphisms in bcr2, rRFs (rearranged bcr2
      restriction fragments) were found in bcr2 as shown in 33% (14 of 42) of our
      patients. By contrast, no rRFs were found in 18 healthy volunteers. Our results
      indicate, that heterogeneous rearrangements in bcr2 may appear in addition to
      BCR/ABL rearrangements involving M-bcr in Ph+CML.

PMID- 1362729
TI  - Determination of Taxotere in human plasma by a semi-automated high-performance
      liquid chromatographic method.
AB  - A rapid, selective and reproducible high-performance liquid chromatographic
      (HPLC) method with ultraviolet detection was developed for the determination of
      the anti-cancer agent Taxotere in biological fluids. The method involves a solid
      phase extraction step (C2 ethyl microcolumns) using a Varian Advanced Automated
      Sample Processor (AASP) followed by reversed-phase HPLC. The validated
      quantitation range of the method is 10-2500 ng/ml in plasma with coefficients of
      variation < or = 11%. The method is also suitable for the determination of
      Taxotere in urine samples under the same conditions. The method was applied in a
      phase I tolerance study of Taxotere in cancer patients, allowing the
      pharmacokinetic profile of Taxotere to be established.

PMID- 1362730
TI  - Expression of D2 dopamine receptor mRNA in the arterial chemoreceptor afferent
      pathway.
AB  - Dopamine is a major neurotransmitter in the arterial chemoreceptor pathway. In
      the present study we wished to determine if messenger RNAs for dopamine D1 and D2
      receptor are expressed in carotid body (type I cells), in sensory neurons of the
      petrosal ganglion which innervate the carotid body and in sympathetic neurons of
      the superior cervical ganglion. We failed to detect D1 receptor mRNA in any of
      these tissues. However, we found that D2 receptor mRNA was expressed by
      dopaminergic carotid body type I cells. D2 receptor mRNA was also found in
      petrosal ganglion neurons that innervated the carotid sinus and carotid body. In
      addition, a large number of sympathetic postganglionic neurons in the superior
      cervical ganglion expressed D2 receptor mRNA.

PMID- 1362731
TI  - Fast inhibitory postsynaptic potentials and responses to inhibitory amino acids
      of sympathetic preganglionic neurons in the adult cat.
AB  - Intracellular recordings were obtained from sympathetic preganglionic neurons
      (SPNs) of the intermediolateral nucleus (IML) in slices of upper thoracic spinal
      cord of the anesthetized cat. A total of 44 neurons was studied. Single shock
      stimulation of an area of white matter dorsolateral to the IML, close to the
      recording electrode (< 0.5 mm), evoked fast IPSPs with rise time of 3.8 ms and
      1/2 decay time of 14.7 ms (n = 12). In 17 other cells only fast EPSPs were
      recorded but, after suppression of the EPSPs by the excitatory amino acid
      receptor antagonists CNQX (20 microM) and APV (100-250 microM), fast IPSPs were
      unmasked. The IPSP reversed polarity at -63 mV (-67 mV in the presence of CNQX
      and APV). The reversal potential shifted to a less negative value when the
      extracellular chloride concentration was reduced. The IPSP was reversibly
      abolished by the GABAA receptor antagonist bicuculline in 32% of the cells, by
      the glycine receptor antagonist strychnine in 47% of the cells and by the
      combination of the two in 21% of the cells. The IPSP was abolished by TTX (0.5
      microM), had constant latency and showed no failures during high frequency
      stimulation. The IPSP presumably resulted from the excitation of inhibitory axons
      and/or inhibitory neuron somata with monosynaptic connections to the SPN. Glycine
      and GABA (1-3 mM) produced hyperpolarization associated with decreased membrane
      resistance. Sixty-nine percent of cells responded to both agonists, 19% to
      glycine only and 12% to GABA only. The GABAB agonist baclofen (5 microM) had no
      effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362732
TI  - Central action of alpha-adrenoceptor agents on the baroreceptor reflex.
AB  - In chloralose-anaesthetized cats the effects of intravenous application of the
      alpha 1- and alpha 2-adrenoceptor agonistic and antagonistic agents methoxamine,
      prazosin, B-HT 933 and rauwolscine were tested on baroreceptor reflex,
      sympathetic background activity and blood pressure. Sympathetic activity was
      recorded from the renal nerve and the efficacy of the central transmission of the
      baroreceptor reflex was measured by the duration of the complete inhibition of
      renal nerve activity during electrical stimulation of the left carotid sinus
      nerve. All baroreceptors were denervated by sectioning both carotid sinus and
      vagal nerves. The alpha 1-agonist methoxamine increased baroreceptor-induced
      sympatho-inhibition, sympathetic background activity and blood pressure. The
      alpha 1-antagonist prazosin had the opposite effects. The alpha 2-agonist B-HT
      933 was most effective in augmenting the inhibitory response in sympathetic
      activity to baroreceptor stimulation; sympathetic background activity and blood
      pressure were also decreased. At low doses (50 micrograms/kg) the alpha 2
      antagonist rauwolscine reduced the baroreceptor sympathetic reflex inhibition and
      increased sympathetic activity and blood pressure. The effect of B-HT 933 upon
      the baroreceptor reflex could be completely antagonized by rauwolscine. These
      findings demonstrate a very effective facilitation of the baroreceptor reflex
      transmission by stimulation of central alpha 2-adrenoceptors. Through such
      humoral-neuronal interaction circulating catecholamines are likely to modulate
      cardiovascular control.

PMID- 1362733
TI  - Growth hormone therapy in normal short children induces a transitory decrease in
      plasma growth hormone releasing hormone levels and in human growth hormone
      responsiveness to exogenous growth hormone releasing hormone.
AB  - A three-month study of the effect of growth hormone (hGH) therapy (0.1 U/kg/day
      sc) on plasma levels of GH releasing hormone (GHRH), somatostatin and insulin
      like growth factor I (IGF-I) and on the hGH responsiveness to exogenous GHRH was
      carried out in 32 prepubertal short-stature children with normal GH secretion.
      Blood samples were collected prior to initiation of therapy, and at 5, 30 and 90
      days of onset of therapy, as well as 2 and 90 days after termination of therapy.
      The nonconventional hGH therapy induced an increase in serum IGF-I levels which
      lasted as long as therapy was continued. Plasma GHRH levels showed an early
      transitory decrease after five days of therapy, whereas plasma somatostatin
      levels were unaltered. A slight suppression in hGH responsiveness to exogenous
      GHRH was found at 2 but not at 90 days after termination of hGH therapy. It is
      concluded that nonconventional hGH treatment does not cause permanent changes in
      physiological hGH secretion.

PMID- 1362734
TI  - [Takayasu's disease and pregnancy].
AB  - We report one case of pregnancy in a non-oriental woman who had Takayashu's
      disease. Pregnancy was characterised by toxemia and caesarean section had to be
      carried out at 31 weeks because of fetal distress. The disease did not worsen and
      nor were there any maternal complications but the child died on the 7th day.

PMID- 1362735
TI  - Ciprofloxacin and Salmonella carriage.

PMID- 1362736
TI  - Septicaemia in paediatric intensive-care patients at the Hospital for Sick
      Children, Great Ormond Street.
AB  - A review of nosocomial septicaemia in paediatric intensive care in a tertiary
      referral setting was undertaken for a 33-month period (1988-90). This involved
      six units: Cardiothoracic surgery; Neonatal surgery; general medical; Renal
      dialysis/transplant; Haematology/Oncology and Infectious disease/Immunology. The
      latter two units undertake bone marrow transplantation. During the study period,
      10,719 admissions were made to these areas and 624 episodes of septicaemia were
      documented in 464 children. The frequency of septicaemia per 100 admissions
      ranged from 1.5 in the Renal Transplant Unit to 17.3 in the Haematology/Oncology
      unit. Over 60% of all septicaemic episodes occurred in children in the
      Haematology/Oncology and Cardiac Units. Gram-positive organisms were responsible
      for 66% of episodes, Gram-negative organisms for 17% and fungi for 3%.
      Polymicrobial episodes accounted for 13%. Coagulase-negative staphylococci were
      the most frequent isolates overall (43% of episodes in pure culture, and a
      further 6% in combination with other organisms). Staphylococcus aureus was
      associated with 10% of episodes, Enterobacteriaceae with 9% and Pseudomonas spp.
      6% among which environmental pseudomonads predominated. Anaerobes and Haemophilus
      influenzae were each isolated in less than 1% of episodes.

PMID- 1362737
TI  - Multiresistant Klebsiella pneumoniae in a neonatal nursery: the importance of
      maintenance of infection control policies and procedures in the prevention of
      outbreaks.
AB  - During a 3-week period, nine babies in the neonatal unit of a large teaching
      hospital in Durban were infected or colonized with Klebsiella pneumoniae
      resistant to a range of antimicrobial agents including amikacin and cefotaxime.
      Resistance to cefotaxime was reduced by clavulanic acid in vitro suggesting
      production of extended-spectrum beta-lactamase activity. All the isolates had the
      same antibiotic resistance profile, belonged to the same serotype (K17), were non
      typable with bacteriophages, and had identical plasmid profiles indicating that
      they belonged to the same strain. During a 1-day microbiological survey of the
      ward, the outbreak strain was isolated from the nose and hands of a doctor based
      in the nursery and from the hands of a nurse and the mother of an infected baby.
      The strain was also isolated from nine of 67 environmental samples. Investigation
      revealed that infection control practices which had been instituted following a
      previous outbreak in the nursery with multi-resistant methicillin-resistant
      Staphylococcus aureus (MRSA) were not being adhered to. The re-introduction and
      strict enforcement of these procedures under the supervision of an Infection
      Control Nurse resulted in the abrupt end of the outbreak.

PMID- 1362738
TI  - Long-term carriage, and transmission of methicillin-resistant Staphylococcus
      aureus after discharge from hospital.
AB  - The purpose of this study was to determine whether patients who become carriers
      of methicillin-resistant Staphylococcus aureus (MRSA) during their stay in
      hospital, remain colonized after discharge. Thirty-six patients colonized with
      MRSA during one of three outbreaks at Utrecht University Hospital (1986-89) were
      screened 2 or 3 years after they had become carriers. Patients were also
      interviewed to determine factors contributing to persistent carriage, such as
      antibiotics, re-admissions to the hospital, presence of skin lesions and chronic
      diseases. At the same time transmission of MRSA to family members was determined.
      The epidemic MRSA strain was still found in three patients (8%). One was a cystic
      fibrosis patient who had had frequent re-admissions to the hospital and had
      received several course of antibiotic treatment. Both of the other patients had
      skin lesions: a fistula and a colostomy respectively. None of the 44 family
      members of the patients was colonized or infected with MRSA. We conclude that
      long-term MRSA carriage occurs with low frequency and is comparable to persistent
      carriage of methicillin-sensitive Staphylococcus aureus (MSSA). Transmission of
      MRSA to healthy individuals in an antibiotic-free environment is a rare event.

PMID- 1362740
TI  - beta-Lactamase substrate profiles of coagulase-negative skin staphylococci from
      orthopaedic inpatients and staff members.
AB  - Three different beta-lactamase substrate profiles were identified in 95 isolates
      of coagulase-negative staphylococci (CNS), of 57 different phenotypes, from 16
      orthopaedic inpatients and staff members in one ward, by applying a bacterial
      whole-cell assay based on the hydrolysis of cefazolin, cephaloridine and
      nitrocefin. The typability of the assay was 93%, and 91% of the CNS isolates
      could be classified. To assess the discrimination between the beta-lactamase
      profiles obtained in the whole-cell assay, beta-lactamase extracts from 19 of the
      CNS isolates were used for estimation of their relative beta-lactamase substrate
      affinity index (RSAI). The RSAI assay was able to type previously unclassifiable
      or nontypable isolates. Two of the profiles obtained with the whole-cell assay
      were similar to those of the Staphylococcus aureus controls producing A or D and
      B or C beta-lactamases respectively. The distribution of beta-lactamase substrate
      profiles among the CNS isolates indicated an efficient spread of these drug
      resistance genes.

PMID- 1362739
TI  - A study of coagulase-negative staphylococci with reference to slime production,
      adherence, antibiotic resistance patterns and clinical significance.
AB  - Two hundred and fifty-one strains of coagulase-negative staphylococci (CNS)
      isolated from patients in hospital and the community were investigated for slime
      production and adherence as indicators of pathogenicity. Staphylococcus
      epidermidis formed 68.5% (126) of the isolates of CNS from blood and central
      venous catheter (CVC) tips, of which 46.0% (58) were slime-positive and adherent.
      Clinically significant infections were associated with 55.2% (32) of the slime
      positive adherent strains isolated and 11.1% (four) of slime-negative non
      adherent strains of S. epidermidis. For other species of CNS isolated from blood
      and CVC tips 74.1% (43) were slime negative non-adherent and 18.6% (eight) of
      these were considered clinically significant isolates while none of the slime
      positive adherent strains were associated with a clinically significant
      infection. Slime production and adherence were not characteristic properties of
      CNS causing community-acquired urinary tract infection or colonizing the nasal
      mucosa. It is concluded that slime production and adherence had a limited role in
      the differentiation between clinically significant and contaminant strains
      isolated from blood cultures; however, the absence of slime and adherence in
      isolates of S. epidermidis suggested a lack of pathogenicity.

PMID- 1362741
TI  - Pseudobacteraemia with multiply-resistant Klebsiella pneumoniae resulting from
      contamination from the blood gas machine on a neonatal unit.
AB  - Klebsiella pneumoniae with an unusual antibiotic susceptibility pattern was
      isolated from blood cultures of seven unwell premature babies on the Special Care
      Baby Unit. Although the organism was sensitive to cefuroxime it was resistant to
      ceftazidime. It was also resistant to gentamicin, tobramycin, netilmicin,
      piperacillin and aztreonam but sensitive to ciprofloxacin, imipenem and amikacin.
      On extensive investigation to trace the source, a K. pneumoniae with the same
      susceptibility pattern as that obtained from blood cultures was isolated from the
      probe and probe cover on the blood gas machine but not from any other
      environmental samples or clinical specimens. Where clinically indicated,
      antibiotics were used to treat these babies, with success. The difficulty,
      however, of differentiating between true septicaemia and pseudobacteraemia could
      be enormous as withholding treatment will have disastrous consequences in genuine
      cases of bacteraemia.

PMID- 1362742
TI  - Catheter-associated septicaemia due to Trichosporon capitatum.

PMID- 1362743
TI  - Efficacy of 'Mediphen', a phenolic disinfectant.

PMID- 1362745
TI  - Therapeutic alternatives in common infections. Proceedings of a symposium at the
      1st International Congress on the Management of Infection. Amsterdam, April 1992.

PMID- 1362744
TI  - Handwashing during MRCP examinations.

PMID- 1362746
TI  - Single-dose amoxycillin-clavulanic acid vs. cefotetan for prophylaxis in elective
      colorectal surgery: a multicentre, prospective, randomized study. The PRODIGE
      Group.
AB  - A prospective, multicentre, randomized trial was carried out in 19 hospitals in
      order to compare the efficacy of amoxycillin-clavulanic acid with cefotetan as
      antibiotic prophylaxis in patients undergoing elective colorectal surgery. Since
      the main purpose of the study was to demonstrate equivalence between the two
      regimens, the protocol planned the inclusion of 200 patients. Eligible patients
      were randomly assigned to receive either amoxycillin-clavulanic acid (2.2 g) or
      cefotetan (2 g) in a single infusion on the induction of anaesthesia. Failure of
      prophylaxis was defined as occurrence of infection of intestinal origin, either
      minor (wound cellulitis) or major (abscess, peritonitis, septicaemia) within the
      30-day postoperative period. Among 221 randomized patients, 208 (105 amoxycillin
      clavulanic acid, 103 cefotetan) aged 66 +/- 12 years (mean +/- SD) were evaluated
      while 13 were withdrawn. Colorectal cancer was the indication for surgery in 73%
      of cases. Eleven (10 +/- 6%, 95% confidence interval) and 13 (13 +/- 7%) failures
      were observed in the amoxycillin-clavulanic acid and cefotetan groups (P = 0.63
      chi-square test) respectively. Most infections occurred before the 10th
      postoperative day (8% failures at this time, estimated by the Kaplan-Meier
      method). The results of the trial demonstrate that amoxycillin-clavulanic acid
      and cefotetan have similar efficacy when used for prophylaxis of infection after
      elective colorectal surgery.

PMID- 1362747
TI  - Prophylaxis and treatment of infections complicating abdominal surgery.
AB  - The suitability of commonly used antimicrobial regimens for prophylaxis in
      abdominal surgery and treatment of intra-abdominal sepsis is discussed. These
      various therapies are often limited in their usefulness by the range of
      microorganisms against which they are effective and thus, to extend the
      antimicrobial cover, agents may be combined. Some forms of therapy may produce
      adverse effects in susceptible patients, thus limiting their use to certain
      groups, or there may be cost constraints. Beta-lactamase-inhibiting compounds
      appear to offer an optimal combination of a broad spectrum of activity against
      aerobic and anaerobic microorganisms, minimal toxicity and reasonable cost.

PMID- 1362748
TI  - Prospective, randomized study comparing amoxycillin-clavulanic acid and
      cefamandole for the prevention of wound infection in high-risk patients
      undergoing elective biliary surgery.
AB  - The efficacy of amoxycillin-clavulanic acid for prevention of postoperative wound
      infection was compared with that of cefamandole in 150 patients at risk for
      infected bile while undergoing elective biliary surgery in a prospective,
      randomized study. The two groups were comparable for age, sex, risk factors,
      operative procedures and positive bile cultures. Similar numbers of patients had
      an uncomplicated postoperative course (amoxycillin-clavulanic acid 70%;
      cefamandole 73%). Four patients in each group developed wound infection. The
      incidence of postoperative pneumonia, urinary tract infection and number of days
      (+/- SD) in hospital (amoxycillin-clavulanic acid 10.1 +/- 4.7; cefamandole 9.7
      +/- 5.6) were similar. The efficacy of amoxycillin-clavulanic acid and
      cefamandole in preventing wound sepsis in high-risk patients undergoing biliary
      surgery was similar. Economic considerations may favour the use of amoxycillin
      clavulanic acid.

PMID- 1362749
TI  - Postoperative complications due to methicillin-resistant Staphylococcus aureus
      (MRSA) in an elderly patient: management and control of MRSA.
AB  - An elderly lady was admitted to hospital for elective resection of an
      adenocarcinoma of the colon. Following an anastomotic leak she developed intra
      abdominal sepsis and underwent abdominal drainage of pus. During recovery from
      her second operation, she developed pneumonia and a bacteraemia due to
      methicillin-resistant Staphylococcus aureus (MRSA). She was treated with
      vancomycin and co-trimoxazole and survived without further sequelae. Details of
      the development and treatment of this case are discussed. Procedures for the
      control and eradication of MRSA infections in hospitals are reviewed.

PMID- 1362750
TI  - Community-acquired pneumonia.
AB  - The aetiology of community-acquired pneumonia is reviewed, and the identification
      of the most likely pathogens, based on clinical presentation, is discussed. By
      far the major pathogen in community-acquired pneumonia is Streptococcus
      pneumoniae; the relative frequency of other pathogens, and particularly the
      atypical pneumonias caused by Mycoplasma and Legionella spp., will depend on
      local epidemiological factors. The diagnostic tests to confirm diagnosis and
      subsequent treatment of these infections are reviewed.

PMID- 1362751
TI  - Activity of amoxycillin-clavulanic acid against Legionella pneumophila in vitro
      and in an experimental respiratory infection model.
AB  - Amoxycillin and clavulanic acid show good activity against Legionella pneumophila
      in vitro, and synergy has been observed between the two agents. However, in
      tissue culture studies, amoxycillin was inactive against intracellular
      legionellae, whereas clavulanic acid and amoxycillin plus clavulanic acid were as
      effective as erythromycin in preventing bacterial growth. These latter findings
      were reflected in the results of therapy of a L. pneumophila pneumonia in the
      neutropenic rat. Amoxycillin was ineffective in reducing bacterial counts in the
      lungs of infected animals, but clavulanic acid and amoxycillin-clavulanic acid
      produced bactericidal effects similar to those of erythromycin. The data
      illustrate the bactericidal activity of amoxycillin-clavulanic acid and
      clavulanic acid against intracellular L. pneumophila in contrast to the lack of
      activity of amoxycillin.

PMID- 1362752
TI  - Comparative clinical and microbiological study of amoxycillin-clavulanic acid and
      ciprofloxacin in acute purulent exacerbations of chronic bronchitis.
AB  - In a retrospective study, the clinical and microbiological efficacy of
      amoxycillin-clavulanic acid and ciprofloxacin were evaluated in outpatients
      observed within the previous year who were affected by acute purulent
      exacerbations of chronic bronchitis. Of the 95 patients included in the trial, 50
      received amoxycillin 875 mg-clavulanic acid 125 mg 8-hourly for 10 days and 45
      received ciprofloxacin 500 mg 12-hourly before meals for 10 days. Of the
      amoxycillin-clavulanic acid-treated patients, 90% showed clear clinical
      improvement and in 10% treatment failed. In the ciprofloxacin group, 75.5% of
      patients showed improvement and in 24.5% treatment failed. All pathogens isolated
      prior to therapy were susceptible to the antibiotic used for therapy. At the end
      of treatment, in the amoxycillin-clavulanic acid-treated group, 84% of strains
      were eradicated and 8% persisted; others were superinfections. In the
      ciprofloxacin group, 57.7% of strains were eradicated, 26.6% persisted and 15.5%
      were superinfections. No clinically significant side effects were observed in
      either group. Overall, amoxycillin-clavulanic acid demonstrated superior clinical
      and microbiological efficacy to ciprofloxacin, although this might be
      attributable to the higher proportion of aerobic Gram-negative pathogens in the
      ciprofloxacin group.

PMID- 1362753
TI  - The management of acute, serous and chronic otitis media: the role of anaerobic
      bacteria.
AB  - Otitis media (OM) is a common childhood disease and one which can cause
      significant morbidity. A knowledge of the pathogens responsible for OM enables
      the most appropriate treatment regimen to be selected and thus minimizes further
      complications which may require hospital admission and surgery. The microbiology
      of acute, serous and chronic OM is reviewed, with particular regard to the role
      of anaerobic bacteria. Anaerobes, mainly Gram-positive cocci, have been recovered
      from 25% of the ear aspirates of patients with acute otitis media. In a study of
      serous OM, anaerobic bacteria were recovered in 12% of the culture-positive
      aspirates. The predominant anaerobes were Gram-positive cocci and pigmented
      Prevotella. Several studies have reported the recovery of anaerobes from about
      50% of patients with chronic OM and those with cholesteatoma. The predominant
      anaerobes were Gram-positive cocci, pigmented Prevotella, Porphyromonas sp.,
      Bacteroides spp. and Fusobacterium spp. Many of these organisms produce beta
      lactamase which might have contributed to the failure of the patients to respond
      to penicillins. The appropriate antimicrobial therapy for acute, serous and
      chronic otitis media is discussed.

PMID- 1362754
TI  - In-vitro bactericidal activity of four oral antibiotics against pathogens
      responsible for acute otitis media in children.
AB  - This study was designed to test the in-vitro activity of four oral antibiotics
      against the four microorganisms most frequently isolated in acute otitis media:
      beta-lactamase-positive Haemophilus influenzae (N = 10), beta-lactamase-positive
      Moraxella catarrhalis (N = 10), penicillin-sensitive Streptococcus pneumoniae (N
      = 11) and methicillin-sensitive Staphylococcus aureus (N = 10), by the
      bactericidal curve method. Bactericidal kinetics were determined for
      concentrations of antibiotic equivalent to those found in the middle ear after
      treatment: amoxycillin-clavulanic acid (2.5 mg l-1/0.6 mg l-1 and 2.5 mg l-1/1.2
      mg l-1), cefaclor (1 mg l-1), erythromycin (0.5 mg l-1) and
      erythromycin/sulfisoxazole (0.2/3 mg l-1). The inoculum was of 10(6) colony
      forming units (cfu) ml-1. The bacterial counts were performed after 5 h and 24 h
      using a spiral inoculator system. The results showed that amoxycillin-clavulanic
      acid had rapid bactericidal activity (< 24 h) on the tested organisms at each of
      the doses used (reduction < or = 3 log10 cfu ml-1) which was not observed with
      the other antibiotics at either 5 or 24 h. Erythromycin alone or combined with
      sulfisoxazole had a bacteriostatic effect on Moraxella catarrhalis and
      Streptococcus pneumoniae but not on Haemophilus influenzae or Staphylococcus
      aureus. Cefaclor had no bactericidal action under these conditions.

PMID- 1362756
TI  - Irradiation of Langmuir-Blodgett multilayer preparations of phospholipids and a
      fatty acid. 1: Effect of UV radiation.
AB  - Langmuir-Blodgett (LB) preparations containing stacked monolayers of
      phospholipids or stearic acid were irradiated with UV light and the electric
      conductance perpendicular to the planes of the monolayers was measured. There was
      no observable change of conductance when LB preparations of stearic acid were
      irradiated. For LB preparations of phospholipids, a rise of conductance,
      dependent on dose rate, was observed, reaching an equilibrium level after a few
      hours. After irradiation the conductance fell with a temperature-dependent time
      constant, and eventually reached a final level a little above the initial value.
      A three-state model is proposed for the LB phospholipid preparations. This
      suggests that the absorption of one photon raises a molecule from the ground to
      an excited state; and the absorption of a second photon carries it into a damaged
      but repairable or metastable state.

PMID- 1362755
TI  - A meta-analysis of the use of amoxycillin-clavulanic acid in surgical
      prophylaxis.
AB  - The efficacy of amoxycillin-clavulanic acid as antibiotic prophylaxis in surgery
      has been assessed in numerous clinical studies, chiefly in abdominal and
      gynaecological surgery. A meta-analysis of 21 trials covering 2685 patients given
      amoxycillin-clavulanic acid and 2220 patients given comparator regimens is
      presented. Monotherapy with amoxycillin-clavulanic acid was as effective as the
      comparators, including combination regimens utilizing gentamicin or
      metronidazole, in preventing wound infections (median wound infection rates were
      6% and 10% respectively). The antibacterial activity of amoxycillin-clavulanic
      acid covers the broad range of aerobic Gram-negative and anaerobic organisms that
      have a major role in postoperative infections. In addition, amoxycillin
      clavulanic acid may have benefits in terms of convenience, tolerance and cost.

PMID- 1362757
TI  - Irradiation of Langmuir-Blodgett multilayer preparations of phospholipids and a
      fatty acid. 2: Effect of X-radiation.
AB  - X-irradiation of Langmuir-Blodgett (LB) preparations of stearic acid with doses
      up to a few thousand Gy produced no change of measured electrical conductance in
      the direction perpendicular to the stacked monolayers. However, irradiation of LB
      preparations of phospholipids resulted in increased conductance. The effect
      depended on dose, but not on dose rate and, unlike the corresponding effect of UV
      radiation, did not reverse at room temperature. For doses up to about 2 kGy the
      increased conductance fell away over some tens of minutes if the temperature was
      raised above 45 degrees C. For doses between 2 and 60 kGy the conductance
      increased linearly, but less rapidly than the initial rise and the increase was
      only partly reversible by heating. The rate of increase of conductance rose again
      for doses above about 60 kGy and for these doses the increase could not be
      reversed on heating. It is suggested that X-irradiation left molecules in a
      damaged but reversible state similar to that found after UV irradiation; and that
      subsequent excitation and ionization damaged the molecules irreversibly.

PMID- 1362758
TI  - Metal ions protect DNA against strand breakage induced by fast neutrons.
AB  - Single and double strand breaks (SSB and DSB) are induced by fast neutrons in
      plasmid (pBR322) DNA in 1 mM potassium phosphate buffer (pH 7.25). Increasing the
      concentration of monovalent (Na+, Cs+, Li+), divalent (Mg2+, Ca2+) and trivalent
      (Al3+, Co3+ (NH3)6) metal cations strongly decreases the yield of DSB. The extent
      of the observed protection depends on the valence of the cation. The production
      of SSB is only slightly decreased, except for Al3+ and Co3+ (NH3)6, whose effects
      are particularly large (complete protection at 1 and 0.1 mM respectively).
      Circular dichroism spectra show that Al3+ induces an important structural change
      of DNA at the ion concentration where the protection becomes total. This change
      is probably a condensation (collapse), as in the well-known case of Co3+ (NH3)6.
      Our results suggest two mechanisms of protection by metal ions: (i) the induction
      of structural changes of DNA, that render less accessible the critical sites of
      attack by OH. radicals; and (ii) the stabilization of the double helical regions
      between two close-set nicks on opposite strands, that hinders the effective
      double strand breakage of DNA.

PMID- 1362759
TI  - Extracellular DNA level in the blood of irradiated rats.
AB  - There is high-molecular DNA in the blood of unirradiated rats which moves as a
      single fraction during electrophoresis in 0.5% agarose. At short times (2-5 h)
      after gamma-irradiation at doses from 1 to 100 Gy a low-molecular species of DNA
      appears (about 180 nucleotide pairs), the amount of which is directly
      proportional to exposure dose at 5 h after exposure. It has been established by
      Southern hybridization that the low-molecular DNA has few nucleotide sequences
      common with those of the high-molecular DNA, but it shows homologously to genomic
      sequences.

PMID- 1362760
TI  - Radiation-induced chromosome aberrations analysed by fluorescence in situ
      hybridization with a triple combination of composite whole chromosome-specific
      DNA probes.
AB  - Fluorescence in situ hybridization (FISH) with a combination of three composite
      whole chromosome-specific DNA probes for human chromosomes 1, 4 and 12 was used
      to analyse in vitro radiation-induced dicentrics and symmetrical translocations
      in peripheral lymphocytes. Translocations could be rapidly and efficiently
      detected by FISH. Their frequencies were 1.8-fold higher than the frequencies for
      dicentrics at a given dose. The dose-response curves for translocations and
      dicentrics were linear quadratic with a significant higher quadratic component
      for translocations. The application of FISH for scoring stable translocations for
      biological dosimetry of radiation exposures is discussed.

PMID- 1362762
TI  - Inter-individual differences in radiation response shown by an in vitro
      micronucleus assay: effects of 3-aminobenzamide on X-ray treatment.
AB  - Among the methods of biological dosimetry of ionizing radiation, we propose the
      cytokinesis-block micronucleus assay for the measurement of the individual dose
      absorbed. The dose-response curve was determined for in vitro-irradiated
      lymphocytes from 25 individuals. The dose-response relationship, fitted by the
      linear-quadratic function, was F(MN) = 0.015 (+/- 0.0016) + 0.043 (+/- 0.0075).D
      + 0.083 (+/- 0.0045).D2. Our results are compared with those of other authors. 3
      aminobenzamide (3AB) combined with X-rays were used to evaluate the micronucleus
      dose-response relationship in blood from 14 individuals. While it is known that
      3AB inhibits poly(ADP-ribose) polymerase activity in vitro, we demonstrate that
      it also increases the X-ray-induced micronucleus yields. The resulting dose
      response relationship varies from subject to subject. The possibility of using
      this approach to identify the individual radiosensitivity level is discussed.

PMID- 1362763
TI  - An automated flow cytometric micronucleus assay for human lymphocytes.
AB  - A new flow cytometric method is presented for scoring micronuclei (MN) in human
      lymphocytes after in vitro gamma-irradiation. Fifty to fifty-five hours after PHA
      stimulation, the frequency of micronuclei per nucleus and the fraction of cells
      in the second cell cycle were measured using flow cytometry. All data were
      automatically analysed using our DAS-software package. Eight individual linear
      quadratic dose response curves derived from five donors revealed inter- and intra
      individual variabilities of all curve parameters. Since also an age dependence
      was found for spontaneous MN-frequencies and for the linear curve parameter, a
      combined linear-quadratic age-dose-effect model was used to fit the data. The 90%
      prediction intervals show that a reliable individual dose estimation for donors
      aged between 23 and 54 years cannot be achieved for exposures below 1 Gy.

PMID- 1362761
TI  - Lack of differential G2 chromosomal radiosensitivity between non-tumorigenic and
      tumorigenic human hybrid cells (HeLa x skin fibroblasts).
AB  - Previous studies have shown, that for log phase cultures, tumorigenic segregants
      of HeLa x skin fibroblast human hybrid cells are slightly more radiosensitive in
      terms of cell killing than their nontumorigenic parents (Redpath et al. 1985,
      Colman et al. 1988). Other studies have shown that these same tumorigenic
      segregants exhibit a markedly enhanced G2 chromosomal radiosensitivity (Sanford
      et al. 1986) thus offering a possible explanation for the cell killing data. The
      present study set out to examine the G2-phase radiosensitivity of these cells in
      terms of cell killing with the expectation that an enhanced sensitivity in the
      tumorigenic cells would be seen. No enhanced sensitivity was observed. The G2
      chromosomal radiosensitivity was then examined and no differential was seen
      between the non-tumorigenic and tumorigenic cells. This lack of confirmation of
      previously reported studies may be due to some technical differences in the
      experimental protocols.

PMID- 1362765
TI  - Effects of tobacco-smoke on radiation-induced pneumonitis in rats.
AB  - To investigate the effect of exposure to tobacco smoke (TS) on the development of
      irradiation-induced pneumonitis in rats, five groups of animals were investigated
      including controls (C), tobacco smoke exposed (S), irradiated (RNS) and
      irradiated and tobacco smoke exposed (RS). An additional group (RS/NS) was
      exposed to tobacco before irradiation but not afterwards. Rats were exposed to
      diluted mainstream cigarette smoke at a concentration of about 0.4 mg/l in a nose
      only exposure system for 1/day, 5 days/week for 10 weeks. Exposure to TS started
      3 weeks before irradiation in which the basal one-third of both lungs was exposed
      to a single dose of 28 Gy. In previous studies this dose had been shown to cause
      significant pneumonitis. All the animals were killed at 7 weeks after
      irradiation. Examination of the morphology of lung sections showed less pulmonary
      inflammation in the RS group than in the RNS group. This was also reflected in
      the results of bronchoalveolar lavage (BAL) which showed a decline in cell
      recovery and a marked decrease in the numbers of mast cells and neutrophils in
      the RS rats compared with the RNS animals. The concentration of hyaluronan in
      lavage fluid was increased in the RNS and RS/NS group while no increase was found
      in the RS group. A marked increase in BAL protein was also seen in the RNS and
      RS/NS groups as compared with the RS group but all were significantly higher than
      in unirradiated controls. This indicates that smoking suppresses the radiation
      induced inflammation but to a lesser degree affects the radiation-induced
      increase in membrane permeability as reflected by increased protein levels in
      BAL. Moreover, the marked effects on the numbers of mast cells and neutrophils in
      the RS group may indicate that these cells play an important role in the
      mechanism by which tobacco smoke modulates the effects of irradiation. When
      exposure to tobacco smoke was terminated immediately after irradiation (RS/NS),
      the inflammatory response was unaffected.

PMID- 1362764
TI  - Effect of multiple irradiation with low doses of gamma-rays on morphological
      transformation and growth ability of human embryo cells in vitro.
AB  - We have measured expression of transformed phenotypes in human embryo (HE) cells
      repeatedly irradiated with a dose of 7.5 cGy per week throughout the life span of
      these cells in vitro. Irradiation was repeated until the cells had accumulated
      195 cGy at which time the cells had reached the equivalent of their 26th passage
      and samples of cells at several passages were assayed for cell survival by colony
      formation, for mutation at hypoxanthine guanine phosphoribosyl transferase
      (HGPRT) locus and for transformation by focus formation. The lifespan (mean
      population doublings) of multiple irradiated cultures with a total dose of 97.5
      cGy was slightly, but significantly, prolonged over that of controls. For
      example, if cells had accumulated 195 cGy, the maximum number of cell division of
      HE cells in vitro extended to 130-160% of non-irradiated control. Although
      transformed foci were not observed with cells until cells had accumulated 97.5
      cGy, it increased with increasing accumulated dose. No cells, however, showed
      unlimited life span in vitro and also expressed tumorigenicity.

PMID- 1362766
TI  - The effect of whole-body gamma-irradiation on localized beta-irradiation-induced
      skin reactions in mice.
AB  - The combined effects of whole-body radiation and localized radiation trauma have
      received scant experimental attention. However, in the recent accidents at
      Chernobyl and Goiania skin damage from beta-contamination was combined with total
      body radiation and in many cases the skin lesions which covered large surfaces of
      the body were severe and recovery was prolonged. This paper models the
      immunosuppressive effects of whole-body gamma-radiation in the sublethal to
      lethal range (1-11 Gy) on the skin reactions produced by 50 Gy of superficial
      beta-radiation. For gamma ray doses < 4 Gy no synergistic effects were
      detectable. For gamma-ray doses of 4, 6 and 8 Gy there was a 4-5-day prolongation
      in time-course of the skin reaction but no significant exacerbation of its
      severity. The overall time for the resolution of the skin reaction (45 days) was
      also unaffected by the relatively high whole-body doses. These rather surprising
      findings of minimal synergy between whole-body exposure and a localized severe
      beta burn to the skin are perhaps explained by the mismatch between the maximal
      immunosuppression at 2-10 days postirradiation and the timing of the skin damage
      at 10-25 days.

PMID- 1362767
TI  - Cytotoxic and photodynamic effects of Photofrin on sensitive and multi-drug
      resistant Friend leukaemia cells.
AB  - To study cross-resistance to Photofrin (PF) photosensitization, a Friend
      leukaemia cell line (ADM-RFLC) with a high level of multi-drug resistance (MDR)
      and the parental sensitive cell line (FLC) have been used. PF uptake measured by
      HPLC shows a similar intracellular drug accumulation in both cell lines. The
      ID50s for cell growth inhibition by PF are also similar after exposure in the
      dark in the two cell lines, while after illumination they are slightly lower in
      ADM-RFLC than in FLC cells. Moreover, verapamil, known to reverse the MDR
      phenotype induced by P-glycoprotein over-expression (the drug efflux mechanism),
      affects equally ADM-RFLC and FLC cells sensitivity to PF. In addition,
      photodynamic treatment with PF did not reverse the resistance to rhodamine 123
      and aclarubicin, but partly reverses resistance of ADM-RFLC cells to antitubulin
      drugs such as vinblastine or vincristine. These latter results could have
      clinical application in the treatment of tumours expressing the MDR phenotype.

PMID- 1362769
TI  - The Telluride Symposium on V-ATPases. Proceedings.

PMID- 1362768
TI  - Role of membrane components in thermal injury of cells and development of
      thermotolerance.
AB  - Exposure of cells to hyperthermia induces a transient resistance to subsequent
      heat treatment. The specific mechanisms responsible for hyperthermic cell killing
      and thermotolerance development are not well understood. It seems that heat may
      induce at least two different states of thermotolerance, of which one is
      dependent on protein synthesis. The expression of thermotolerance may include
      multiple cytoplasmic and membrane components. A number of studies have indicated
      that membranes play an important role in governing the thermal injury of cells.
      It seems, therefore, that heat denatured plasma membrane proteins may be a
      potential target for thermal stress and a trigger for the induction of
      thermotolerance. The localization of heat shock proteins in the plasma membrane
      and the suggestion of thermal resistance in enucleate erythrocytes support this
      suggestion. However, a direct relationship between the plasma membrane and
      hyperthermic killing or development of thermotolerance has not been found.

PMID- 1362770
TI  - The role of V-ATPase in neuronal and endocrine systems.
AB  - Synaptic vesicles have important roles in the neural transmission at nerve
      terminals: the storage and the controlled exocytosis of neurotransmitters. At
      least two different factors are responsible for the concentration process: the
      vacuolar-type H(+)-ATPase (V-ATPase), establishing an electrochemical gradient of
      protons, and specific transport systems for transmitters. We will discuss our
      recent progress on the energy-transducing systems in synaptic vesicles: (1)
      structural aspects of V-ATPase; (2) energy coupling of transport of transmitters;
      (3) reconstitution of transporters; (4) effects of neurotoxins and neuron
      blocking agents; (5) function of synaptic-vesicle-like microvesicles from
      endocrine tissues.

PMID- 1362771
TI  - Pathobiology and clinical studies concerning diseases of the basal ganglia.
      Symposium proceedings.

PMID- 1362772
TI  - [Contribution of proliferating cell nuclear antigen to prognostic evaluation of
      carcinomas of the maxillary sinus].
AB  - Proliferating cell nuclear antigen (PCNA) is a nuclear protein, synthesized in
      the late G1 and S phases of the cell cycle. Therefore, it is considered to be
      closely related to cell proliferation. The contribution of PCNA to prognostic
      evaluation of the disease was investigated in 42 squamous cell carcinomas of the
      maxillary sinuses, retrospectively. Histological sections were prepared by
      formalin-fixation, paraffin-embedding and staining with monoclonal antibody to
      PCNA (DAKO, PC10) using the Avidin-biotin peroxidase complex method. The
      percentage of tumor cells with positive staining for PCNA ranged from 26.3 to
      92.3% (average; 61.7%). In order to evaluate PCNA in terms of prognosis, five
      year survival rates in the following two groups were compared. One included cases
      with a PCNA positive rate above the mean level and the other, those below the
      mean level. Five year survival rate was 30.4% in the group with a higher positive
      rate, but 42.1% in the group with the lower rate. However, the difference in
      survival rate between the two groups was not statistically significant. In
      addition, no correlations either between the rate of PCNA positivity and T
      classification of tumors or between the degree of tumor cell differentiation and
      metastasis to neck lymph nodes were obtained. Further study is necessary to
      evaluate PCNA as a prognostic marker in human malignancy.

PMID- 1362774
TI  - Genetics and gene expression in mental illness. Proceedings of an International
      Workshop. Venice, 28-31 October 1991.

PMID- 1362773
TI  - The pediatric nurse practitioner and the physician assistant: how are we
      different?
AB  - Changing health care needs over the past 30 years have created new roles for
      professionals in advanced health care practice settings. As new roles continue to
      evolve, educational preparation and clinical experiences must be considered when
      determining the most appropriate health care provider for a particular
      specialization. Although similarities exist between the PA and PNP, the extent of
      pediatric didactic and clinical experiences is limited in most PA programs. Only
      one program is identified by the American Academy of PAs as a child health PA
      program. PNP education provides the nurse in an advanced practice role with an
      extensive background in normal growth and development, family counseling, health
      promotion, and management of common pediatric problems and chronic illnesses. The
      PNP is a registered nurse who is experienced in the care of children before
      pursuing an advanced degree as a PNP. In comparison, many PAs are not required to
      hold a professional degree before enrollment in a PA program. Although students
      entering PA programs may have experience in health-related fields before
      enrollment, few are specialized in the care of children. The PA program is
      designed to prepare the student to assist the physician with diagnosis and
      treatment in primary care with limited exposure to pediatrics. In comparison, the
      PNP spends the entire educational program of study gaining expertise in the care
      of children from infancy to adolescence. Because of advanced educational
      preparation, the PNP is in a unique position to contribute substantially to the
      total care of the child and family.

PMID- 1362775
TI  - Update on the search for DNA markers linked to manic-depressive illness in the
      Old Order Amish.
AB  - In this report we describe our efforts to identify a gene involved in bipolar
      illness using a large, multigenerational Old Order Amish pedigree with many
      affected individuals. The original collection of cell lines from Amish pedigree
      110 has been extended to include 169 individuals. We have used over 250 markers
      spaced at approximately 20 centiMorgans that detect restriction length fragment
      polymorphisms, but no LOD scores greater than 3 have been obtained from pairwise
      linkage analyses. We are expanding our collection of cell lines from both normal
      and affected family members and updating our diagnostic data as we continue our
      systematic screening of the genome for a gene involved in bipolar illness.

PMID- 1362776
TI  - Mapping psychiatric disease genes: impact of new molecular strategies.
AB  - Genetic mapping of genes which predispose to psychiatric illness is discussed in
      relation to recent developments in molecular genetic technology. Among the
      psychiatric disorders, the mechanism by which genetic factors contribute to
      illness is poorly understood, and the classification of phenotype (ill-status) is
      extremely complicated. These uncertainties, together with other complicating
      factors, tend to undermine the effectiveness of genetic linkage analysis. Two
      very powerful new molecular strategies have the potential to improve the overall
      gene mapping effort. First, new applications of polymerase chain reaction (PCR)
      technology will allow laboratories to generate much more genetic data than has
      been previously possible. Some of the factors which confound psychiatric linkage
      analysis should be mitigated by the larger data sets that will be generated with
      this technology. Second, the cloning of large segments of human chromosomes into
      yeast artificial chromosomes (YACs) has given rise to strategies to clone and
      catalog the entire human genome. The goal of constructing overlapping YAC clones
      (contigs) end-to-end across each human chromosome now appears imminent. This
      development will have immense effect upon our ability to identify disease genes.

PMID- 1362777
TI  - Nonhuman behavioral models in the genetics of disturbed behavior.
AB  - The development of the association method in which genetic markers match
      quantitative traits had led to quantitative trait loci (QTL) interval mapping.
      The association method has been extensively used in animal behavior genetics.
      Animal research allows more suitable linkage studies and detailed assessment of
      cellular and subcellular components of the central nervous system that may play a
      crucial role in the development susceptibility to behavioral disorders. Moreover,
      experimental designs in the laboratory setting allow genotype x environment
      interactions to be controlled, thus possibly providing more information on the
      role of nongenetic factors in gene expression. Experimental results are discussed
      which indicate that animal studies will provide a sort of test for hypotheses
      arising in clinical settings, allowing gene-product and product-behavior pathways
      to be examined at molecular levels when the gene accounts for a very small amount
      of genetic variance. In such a perspective, new molecular biology approaches and
      behavior genetics in nonhuman species could provide useful tools in the
      assessment of the genetic as well as nongenetic factors that lead to
      psychopathology.

PMID- 1362778
TI  - Sulfasalazine in early rheumatoid arthritis. The Australian Multicentre Clinical
      Trial Group.
AB  - One hundred and five patients with a diagnosis of early nonerosive rheumatoid
      arthritis (RA) were randomized to receive enteric coated sulfasalazine as
      Salazopyrin En-tabs or placebo for 6 months. Sixty-five patients completed this 6
      month treatment period. Patients taking sulfasalazine were significantly better
      than those taking placebo in terms of Ritchie articular index, number of swollen
      and tender joints and erythrocyte sedimentation rate. The sulfasalazine group
      also demonstrated a significant fall in serum hyaluronic acid, IgM rheumatoid
      factor and C-reactive protein concentration. Side effects leading to withdrawal
      from treatment occurred in 14 of the sulfasalazine group and 4 of the placebo
      group. The most common side effects of patients taking sulfasalazine were rashes,
      liver function test abnormalities and gastrointestinal upsets. Our study
      demonstrates the efficacy of sulfasalazine in early RA.

PMID- 1362779
TI  - Systemic lupus international collaborative clinics: development of a damage index
      in systemic lupus erythematosus.

PMID- 1362780
TI  - Negative seroactivity to HTLV-1 in Sephardic Jews and Arabs with Behcet's
      disease.

PMID- 1362781
TI  - [Polymorphism of T cell receptor genes and hyper-production of cytokines: their
      possible contribution to the pathogenesis of IgA nephropathy in ddY mouse].
AB  - The ddY mouse has been used as the spontaneous model animal of human IgA
      nephropathy (IgAN), because kidney lesion as well as immunological abnormalities
      resemble that of human IgAN. The intensity of mesangial IgA deposition in
      neonatally thymectomized ddY mice, in which T cell function was impaired, was
      less severe, indicating that cytokines from T cells determine the amount of
      mesangial IgA deposition. Therefore ddY mouse may possess a large amount of
      cytokines due to hyperactivity of T cells. To elucidate the reason for T cell
      hyperactivity in ddY mice, genetic polymorphism of T cell receptor genes was
      examined. Though restriction fragment length polymorphism (RFLP) of alpha and
      beta chain genes is the same as that of normal mice, the RFLP of the gamma chain
      is unique. Since T cells bearing gamma chain are observed frequently in the
      tonsil gland or intestinal intraepithelium, which are indispensable lymphoid
      tissues for IgA production, an uncommon DNA sequence of the gamma chain could
      contribute to the pathogenesis of IgAN.

PMID- 1362782
TI  - [Proto-oncogene, proliferating cell nuclear antigen, perforin and growth factor
      gene expression in peripheral blood mononuclear cells from patients with IgA
      nephropathy].
AB  - IgA nephropathy, which is widely recognized as one of the most common primary
      glomerulonephritides, is characterized by the constant presence of IgA in the
      glomerular mesangium. We investigated proto-oncogenes, proliferating cell nuclear
      antigen (PCNA), perforin, platelet-derived growth factor (PDGF) and insulin-like
      growth factor (IGF) mRNA expression in peripheral blood mononuclear cells (PBMC)
      obtained from patients with IgA nephropathy, patients with other types of
      glomerulonephritis and healthy age-matched controls. The majority of patients
      with IgA nephropathy showed elevated c-myc, c-fos, c-jun, c-raf, PCNA, perforin,
      PDGF-B chain, and IGF-I and -II mRNA expression in PBMC, while no these mRNA
      expression was detected in PBMC obtained from patients with other types of
      glomerulonephritis or normal controls. A positive correlation was noted between
      mRNA levels and urinary protein excretion. mRNA expression also correlated with
      the histopathological findings in the renal tissue of patients with IgA
      nephropathy. These studies suggest that abnormal regulation of proto-oncogenes,
      PCNA, perforin, PDGF and IGF gene expression in PBMC may be associated with the
      progression of IgA nephropathy and may be useful as an indicator of disease
      activity.

PMID- 1362783
TI  - [The significance of C4 locus II deletion in IgA nephropathy and Henoch-Schonlein
      nephritis and it's correlation with other HLA genes].
AB  - IgA nephropathy and HSP nephritis share some similar immunological abnormalities,
      for example, high IgA serum concentration, existence of IgA-IC, alternative
      pathway activation, monocyte and B-cell activation and the same histological
      findings of renal biopsy. The genetic factors may play an important role in both
      diseases. The increased frequency of homozygous null C4 phenotypes was reported
      in Caucasians. But the regional variation of C4 null alleles were recognized
      distinctly, and the significance of C4 isotype deficiency remained unclear. We
      studied the relationship between IgA nephropathy and Class II and Class III HLA
      antigens in Japanese by not only C4 protein phenotypes but also gene analysis
      (TaqI, Nla IV and EcoO 109). The frequency of C4 protein isotype deficiency was
      the same with control groups, but significantly increased C4 gene deletion was
      observed in both diseases. Neither DR4 nor DQB4/8/9 related to C4 gene deletion,
      but the total C4 serum concentration was lower in gene deletion groups. We could
      not detect any deviation between C4A and C4B locus deletion by Nla IV and EcoO
      109 analysis. Considering the changing process of C4A to C4B, there is a
      possibility that the mechanism of deletion process itself causes the elevated
      sensitivity to the diseases.

PMID- 1362784
TI  - [Renin gene analysis of familial Bartter's syndrome].
AB  - Familial Bartter's syndrome is considered to be an autosomal recessive disease.
      Because an activation of the renin-angiotensin system is a characteristic feature
      of this disease, we evaluated a possible changes in renin gene. However, we could
      not detected any molecular abnormalities of renin gene, i.e. gene duplication,
      insertion/deletion polymorphism, nor peculiar frequencies of renin RFLPs. For
      further study, we must collect large numbers of affected families of this
      disease, and examine more various candidate genes including Cl(-)-transport
      proteins.

PMID- 1362785
TI  - [Effect of famotidine on gastrin cell, somatostatin cell, and prostaglandin E2
      concentration of stomach in experimental pyloric stenosis model].
AB  - We investigated the effect of 4-weeks famotidine administration (15 mg/kg/day) on
      gastrin cell (G-cell), somatostatin cell (D-cell) and prostaglandin E2 (PGE2) of
      gastric mucosa in pyloric stenosis rats. As a result, the increase of G-cell
      number and serum gastrin level in pyloric stenosis rats were potentiated by
      famotidine administration. However, the increase of D-cell number in pyloric
      stenosis was remarkably abolished by famotidine administration, and G/D cell
      ratio was increased accordingly. Moreover, famotidine administration decreased
      PGE2 concentration in fundic mucosa of the stomach without altering PGE2
      concentration in pyloric mucosa. Our results suggested that famotidine
      administration in pyloric stenosis had a possibility to worsen the balance of
      endocrine cell kinetics in stomach, and PGE2 in fundic mucosa would play a roll
      on the proliferation of D-cell in pyloric stenosis.

PMID- 1362786
TI  - Pharmacological characterization of contractile responses induced by alpha 1
      agonists, norepinephrine and clonidine, by selective antagonists of their
      subtypes in rabbit thoracic aorta.
AB  - In the rabbit isolated thoracic aorta, WB 4101 and 5-methylurapidil dose
      dependently shifted the concentration-response curves for norepinephrine to the
      right. Schild plots showed that the inhibition of responses for WB 4101 and 5
      methylurapidil was biphasic, implying that norepinephrine acted through two
      receptor populations. Clonidine produced a concentration-dependent contraction in
      the isolated rabbit thoracic aorta. WB 4101 and 5-methylurapidil antagonized the
      contractions for clonidine, and the Schild plot to both antagonists against
      clonidine yielded a monophasic slope. Schild plots of the results obtained from
      the inhibition by WB 4101 and 5-methylurapidil for norepinephrine in strips
      pretreated with chloroethylclonidine yielded a straight line with a slope of
      unity. Specific binding of [3H]prazosin in the aortic membrane preparations was
      saturable. The Hill coefficient obtained from the inhibition curves for clonidine
      was significantly different from unity. Clonidine interacted with two binding
      sites labelled by [3H]prazosin, but the low affinity site was completely
      eliminated by pretreatment with 10 microM chloroethylclonidine. These results
      suggest that the subtype activated by norepinephrine is different from that
      activated by clonidine, and that norepinephrine-induced contraction through both
      alpha 1A- and alpha 1B-subtypes and clonidine through only the alpha 1A-subtype
      in the rabbit thoracic aorta.

PMID- 1362787
TI  - Dynorphin-(1-13): antinociceptive action and its effects on morphine analgesia
      and acute tolerance.
AB  - Antinociceptive actions and effects of intracerebroventricular (i.c.v.) dynorphin
      (1-13) (DYN) on morphine (MOR) analgesia and acute tolerance were studied in male
      Sprague-Dawley rats. Antinociceptive effect against hind paw pressure was
      produced by 30 micrograms of DYN, but not by 0.5-10 micrograms. Acetic acid
      writhing was inhibited dose-dependently by DYN at the doses of 2-30 micrograms,
      and the order of potency of the anti-writhing effect was beta-endorphin > MOR >
      DYN >> Met-enkephalin. The anti-writhing effect of DYN that was partially
      antagonized by naloxone at 10 mg/kg, s.c. in MOR tolerant rats was the same as
      that in MOR naive rats. The anti-writhing effect of i.c.v.-MOR was increased
      synergistically by DYN. Continuous s.c. (6 mg/kg/hr) and i.c.v. (7.5
      micrograms/rat/hr) infusion of MOR produced antinociception against hind paw
      pressure, which reached maximum (MAX) and attenuated thereafter during MOR
      infusion for 6 hr. The attenuation of antinociception was also produced during
      MOR infusion combined with multiple i.c.v.-injection of DYN. The MAX and area
      under the antinociceptive curve during MOR infusion was not affected by multiple
      injection of DYN, i.e., no effect of i.c.v.-DYN on the development of acute MOR
      tolerance induced by s.c.- and i.c.v.-infusion was observed. In conclusion, the
      anti-writhing effect of i.c.v.-DYN might not be mediated via mu-receptors,
      although DYN increased the anti-writhing effect of i.c.v.-MOR synergistically and
      the development of acute tolerance to MOR (i.c.v., s.c.) was not affected by
      i.c.v.-DYN.

PMID- 1362789
TI  - [Nursing diagnosis. The first regional meeting of the European French-speaking
      Nursing Diagnosis Association].

PMID- 1362788
TI  - Effects of guanosine 5'-triphosphate on the specificity of irreversible alpha 1
      antagonisms by phenoxybenzamine in rabbit thoracic aorta.
AB  - Phenylephrine displacement curves for the specific binding of [3H]prazosin in the
      membrane fraction prepared from rabbit thoracic aorta showed high- and low
      affinity sites with slope factors significantly less than unity. The irreversible
      alpha 1B-antagonist phenoxybenzamine shifted the binding sites to single high
      affinity sites with a slope factor close to unity in the presence of the
      metabolically stable GTP analog GTP gamma-S. These results indicate that
      phenoxybenzamine may have affected selectively the low affinity site to
      phenylephrine in the presence of GTP gamma-S.

PMID- 1362790
TI  - A microscopical assay using a densitometric application of image analysis to
      quantify neurotransmitter dynamics.
AB  - We have attempted to demonstrate the technical requirements and performance of a
      microscopical assay using a densitometric application of image analysis to
      measure immunohistochemical stain intensity. Not surprisingly, the techniques
      required were more demanding than those used for the quantification of field and
      object parameters in the nervous system. The following areas of methodology have
      been shown to be important: (1) use of buffers free of metallic ions for tissue
      processing, (2) selection and titration of first and second layer antibodies, (3)
      reduction and control of fading of fluorescence, (4) selection of microscopical
      and imaging equipment to give accurate, sensitive and uniform representations of
      low-light biological images, and (5) use of appropriate image analysis algorithms
      in order to generate binary images that match the spatial and intensity
      distributions of immunostaining. Incorporation of these techniques into our assay
      system gave sensitive measurements of the time-scale of uptake of 5-hydroxy
      tryptamine (5-HT) into sympathetic nerve terminals. The microscopical assay
      appears to have advantages over alternative approaches used for studies of
      neurotransmitter dynamics, particularly in small, heterogeneous tissue samples.

PMID- 1362791
TI  - Utilization of extracellular lipids by HT29/219 cancer cells in culture.
AB  - Uptake and incorporation of long-chain fatty acids were studied in a human
      colorectal cancer cell line (HT29/219) grown in culture medium supplemented with
      either fetal calf serum (FCS) or horse serum (HS). The cells were grown for 120 h
      with no change of medium; the two major cellular lipid classes, the phospholipids
      and the triacylglycerols, were analyzed at regular time-points. We observed
      significant changes in the concentration of most fatty acids throughout culture,
      and differences in their composition when different sera were used to supplement
      the medium. Minimal levels of free fatty acids were found in the cells,
      indicating a very small "free fatty acid pool". A major difference between the
      cells grown in media supplemented with different sera was the changes observed in
      concentrations of cellular polyunsaturated fatty acids during growth. In cells
      grown with FCS (in which 20:4n-6 is present), the levels of this acid in the
      phospholipid and triacylglycerol fractions declined rapidly during cell growth,
      suggesting further metabolism. In cells grown in medium supplemented with HS,
      18:2n-6 was the major polyunsaturated acid present. There was clear evidence that
      this acid accumulated in the cellular triacylglycerol and phospholipid fractions.
      Furthermore, its concentration did not decline during growth in culture,
      suggesting minimal conversion to other polyunsaturated n-6 acids. Our results
      suggest that fatty acids from additional sources in the medium, for example
      triacylglycerols and phospholipids associated with the lipoproteins, are taken up
      by the cells. There is also indication of cellular fatty acid synthesis,
      particularly of monounsaturated and saturated acids during the culture
      period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362793
TI  - Dominant familial syndromes with endocrine hyperfunction: an additional syndrome?
AB  - At least 8 separate dominant syndromes have been described which have
      hyperfunctioning endocrine tumors as an important component. Scattered reports in
      the literature suggest that there may be an additional syndrome, in which extra
      adrenal paragangliomas (often multiple), pituitary adenomas, and parathyroid
      hyperplasia coexist. Of 3 such cases described to date, 2 have included
      information about the family history, which in each case suggested dominant
      inheritance. This would presumably be a less common syndrome than the others
      recognized previously, so that full evaluation of endocrine findings and family
      history in future cases will be important for developing our understanding of the
      syndrome.

PMID- 1362794
TI  - Neuroleptic malignant syndrome in Malaysia: a university hospital experience.
AB  - The neuroleptic malignant syndrome (NMS) is a potentially fatal complication of
      antipsychotic therapy. A retrospective study of nine patients seen over six years
      at the University Hospital, Kuala Lumpur (UHKL), is described. The estimated
      annualised incidence was 1.2 per 1000 in-patients with psychosis. No ethnic
      difference was detected. Clinical features were similar to experiences elsewhere,
      with wide variability seen in the severity of illness. The neuroleptic drugs
      implicated were haloperidol, trifluoperazine, chlorpromazine, fluphenazine and
      clopenthixol. Treatment consisted of withdrawal of offending drugs and supportive
      measures. Specific therapy was given to five patients. There was one death. At
      follow-up no deterioration was detected. A different neuroleptic drug was
      successfully re-introduced in four patients. In view of the wide usage of major
      tranquillizers, a high degree of clinical awareness of this serious complication
      is necessary for early diagnosis to reduce morbidity and mortality.

PMID- 1362792
TI  - Essentiality of dietary omega 3 fatty acids for premature infants: plasma and red
      blood cell fatty acid composition.
AB  - Pre-term infants, that are not breast-fed, are deprived of vital intrauterine fat
      accretion during late pregnancy and must rely on formula to obtain fatty acids
      essential for normal development, particularly of the visual system. Preterm
      infants (30 wk postconception) receiving human milk were compared to infants
      given one of the following formulae: Formula A was a commercial preterm formula
      with predominantly 18:2 omega 6 (24.2%) and low (0.5%) 18:3 omega 3; Formula B
      was based on soy oil and contained similar 18:2 omega 6 levels (20%) and high
      18:3 omega 3 (2.7%); Formula C was also a soy oil-based formula (20% 18:2, 1.4%
      18:3) but was supplemented with marine oil to provide omega 3 long-chain
      polyunsaturated fatty acids (LCP) at a level (docosahexaenoic acid, DHA, 0.35%)
      equivalent to human milk. At entry (10 days of age), the fatty acid composition
      of plasma and red blood cell (RBC) membrane lipids of the formula groups were
      identical. By 36 wk postconception, the DHA content in lipids of group A was
      significantly reduced compared to that in the human milk and marine oil formula
      groups. Omega-3 LCP results were further amplified by 57 wk with compensatory
      increases in 22:5 omega 6 in both plasma and RBC lipids. Provision of 2.7% alpha
      linolenic acid in formula group B was sufficient to maintain 22:6 omega 3 levels
      equivalent to those in human milk-fed infants at 36 wk but not at 57 wk. Effects
      on the production of thiobarbituric acid reactive substances and fragility of RBC
      attributable to the marine oil supplementation were negligible. The results
      support the essentiality of omega 3 fatty acids for preterm infants to obtain
      fatty acid profiles comparable to infants receiving human milk. Formula for
      preterm infants should be supplemented with omega 3 fatty acids including LCP.

PMID- 1362795
TI  - Molecular cloning and characterization of neurotransmitter transporters.

PMID- 1362796
TI  - Complement mRNA in the mammalian brain: responses to Alzheimer's disease and
      experimental brain lesioning.
AB  - This study describes evidence in the adult human and rat brain for mRNAs that
      encode two complement (C) proteins, C1qB and C4. C proteins are important
      effectors of humoral immunity and inflammation in peripheral tissues but have not
      been considered as normally present in brain. Previous immunocytochemical studies
      showed that C proteins are associated with plaques, tangles, and dystrophic
      neurites in Alzheimer's disease (AD), but their source is unknown. Combined
      immunocytochemistry and in situ hybridization techniques show C4 mRNA in
      pyramidal neurons and C1qB mRNA in microglia. Primary rat neuron cultures also
      show C1qB mRNA. In the cortex from AD brains, there were two- to threefold
      increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in
      part associated with microglia. As a model for AD, we examined entorhinal cortex
      perforant path transection in the rat brain, which caused rapid increases of C1qB
      mRNA in the ipsilateral, but not contralateral, hippocampus and entorhinal
      cortex. The role of brain-derived acute and chronic C induction during AD and
      experimental lesions can now be considered in relation to functions of C proteins
      that pertain to cell degeneration and/or cell preservation and synaptic
      plasticity.

PMID- 1362797
TI  - Release of amino acid neurotransmitters in different cortical areas of conscious
      adult and aged rats.
AB  - The aim of the present study was to investigate whether or not the levels of
      amino acid neurotransmitters change during the normal process of aging in the
      cerebral cortex. In vivo push-pull perfusions were performed in four different
      areas of the cortex of young (3-4 months) and aged (24-26 months) rats: medial
      prefrontal cortex, sulcal prefrontal cortex, parieto-temporal cortex and
      occipital cortex. Extracellular levels of Asp, Glu, Ser, Gln, and Gly were
      analyzed by HPLC-fluorimetric detection. Aspartate, glutamate, and serine showed
      no differences between young and aged animals in any of the four cortical areas
      studied. However, in the aged rats, the levels of glutamine, a precursor of
      acidic amino acid neurotransmitters, were significantly increased in medial
      prefrontal cortex, sulcal prefrontal cortex, and parieto-temporal cortex. No
      changes in glutamine were detected in occipital cortex. These results suggest
      that the extracellular levels of Asp and Glu in the cerebral cortex do not change
      during the normal process of aging possibly due to functional compensations made
      by intact neurons and/or astrocytes. In addition, the increase of glutamine in
      some areas of the cerebral cortex could be indicative of glial (astrocytes)
      proliferation as a result of neuronal degeneration during the normal process of
      aging.

PMID- 1362799
TI  - HLA-DP region gene polymorphism in primary IgA nephropathy: no association.

PMID- 1362798
TI  - Toward modeling age-related changes of attentional abilities in rats: simple and
      choice reaction time tasks and vigilance.
AB  - Fischer-344 rats aged 4, 12, or 18 months were trained in a simple or choice
      reaction time task (SRTT; CRTT). Animals were required to detect a brief (50 ms),
      rarely, and unpredictably occurring signal that was presented either at the
      central panel light (SRTT) or above one of the two levers (CRTT). Animals
      reported detection by pressing either lever (SRTT) or the cued lever (CRTT)
      within 3 s. False alarm rates were obtained from a nonsignal 3-s bin. In
      comparison to younger animals, 18-month-old animals showed a reduced signal
      detectability, and this effect did not interact with practice. These results
      suggest that age affected vigilance and practice did not attenuate this effect.
      The benzodiazepine receptor agonist chlordiazepoxide (at subsedative doses; 1, 3,
      and 5 mg/kg) and the beta-carboline ZK 93 426 (1, 3, and 5 mg/kg) failed to
      affect signal detectability. Scopolamine HBr and MBr impaired detectability and
      responsivity to a similar extent. However, scopolamine MBr, unlike the tertiary
      compound, failed to affect response accuracy in the CRTT. It is speculated that
      the failure of chlordiazepoxide to affect performance was related to low
      processing demands of both tasks. Although these behavioral models show good face
      validity, they do not allow determination of the major components of attentional
      processes (perceptual sensitivity, response criterion, processing capacity).
      Animal behavioral paradigms that allow determination of such components are
      required for the investigation of the neuronal basis of age-related changes in
      attentional abilities.

PMID- 1362800
TI  - Heymann nephritis: a model of human membranous glomerulopathy. A study of the
      role of additional antigens.

PMID- 1362801
TI  - HLA antigen and gene polymorphisms and haplotypes established by family studies
      in membranous nephropathy.

PMID- 1362803
TI  - Immunohistochemical colocalization of tyrosine hydroxylase and estradiol
      receptors in the sheep arcuate nucleus.
AB  - In sheep, the arcuate nucleus contains numerous tyrosine hydroxylase (TH) and
      estradiol receptor (rE2) immunoreactive (IR) perikarya and it has been shown
      previously in this species that catecholaminergic neurons can mediate the gonadal
      steroid action on the reproductive function. In the present study, double
      immunohistochemical labelling with antibodies against TH and rE2 have been used
      to demonstrate the presence of rE2 in TH-IR neurons in the arcuate nucleus where
      the distribution of TH-IR and rE2-IR neurons overlap each other. Only less than
      10% of all the rE2-IR perikarya presented TH immunoreactivity. It was therefore
      hypothesized that either such a low number of double labelled neurons can support
      the effects of estradiol in this area or that the effect of this steroid was
      indirect. In the latter case it might be first mediated by beta-endorphin neurons
      which have been previously described in this nucleus.

PMID- 1362802
TI  - Monoclonal antibodies to glomerular antigens.

PMID- 1362804
TI  - Regulation of the glutamine content of astrocytes by cAMP and hydrocortisone:
      effect of pH.
AB  - It was reported recently that the glutamine content of astrocytes incubated with
      glutamate and ammonium is steeply dependent on the pH of the solution. The
      present study shows that pretreatment of astrocytes with dibutyryl cAMP or with
      hydrocortisone, conditions that induce glutamine synthetase activity, increased
      glutamine content 2.4-fold and 5.3-fold, respectively. Nevertheless, a shift of
      pH from 7.4 to 7.8 increased glutamine content further by 2.7-fold and 3.0-fold,
      respectively. The net rates of uptake of glutamate and export of glutamine varied
      narrowly compared to these very large changes in glutamine content.

PMID- 1362805
TI  - Astrocyte glutamate uptake during chemical hypoxia in vitro.
AB  - Glutamate uptake was measured in primary rat cortical astrocyte cultures exposed
      to sodium azide, 2,4-dinitrophenol, or antimycin A to assess the ability of
      astrocytes to function under hypoxic conditions. Uptake was maintained at 54-63%
      of control values despite maximal inhibition of oxidative ATP production. In
      contrast, the glycolytic inhibitor sodium fluoride (20 mM) reduced glutamate
      uptake by more than 95% when glucose was the only available substrate. These data
      suggest that glutamate uptake is largely maintained during hypoxia provided
      glucose remains available. Astrocyte glutamate uptake may aid neuronal survival
      during conditions such as incomplete ischemia where oxygen but not glucose is
      depleted.

PMID- 1362806
TI  - Semiquantitative analysis of immunoreactivities of tyrosine hydroxylase and
      aromatic L-amino acid decarboxylase in the locus coeruleus of desipramine-treated
      mice.
AB  - The influence of antidepressant drugs on catecholaminergic neuron groups of the
      mouse brain was studied immunohistochemically, using a microphotometric
      semiquantitative method. The immunoreactive level of tyrosine hydroxylase (TH)
      and aromatic L-amino acid decarboxylase (AADC) in the locus coeruleus (LC) was
      significantly decreased after 2 weeks of antidepressant administration. Our
      results suggest that long-term exposure to an antidepressant drug, desipramine,
      significantly affects intracellular catecholamine-synthesizing enzymes. These
      results may suggest some significant roles of the catecholaminergic neuronal
      groups to the action of the tricyclic antidepressant drugs.

PMID- 1362807
TI  - Riluzole inhibits the release of glutamate in the caudate nucleus of the cat in
      vivo.
AB  - When applied locally to the caudate nucleus of the halothane-anaesthetized cat,
      riluzole (10(-5) M) markedly reduced (-57%) the spontaneous release of glutamate.
      This effect seems to be specific, since the efflux of the other amino acids,
      including aspartate was not affected. Indicating further its selective inhibitory
      effect on the spontaneous release of glutamate, the prolonged (90 min)
      application of riluzole (10(-5) M) enhanced the size of the potassium-releasable
      pool of glutamate, but not that of aspartate. This effect of riluzole was not
      noticed with classical anti-glutamatergic drugs, tested in the same conditions.

PMID- 1362808
TI  - Intrathecal somatostatin in the guinea pig: effects on spinal cord blood flow,
      histopathology and motor function.
AB  - In the present investigation, the vasoconstrictive, motor and neurodegenerative
      effects of intrathecal somatostatin (SST) were assessed in guinea pigs implanted
      with lumbar intrathecal catheters. Five consecutive dose increments of SST (5,
      10, 15, 30 and 60 micrograms) to a total of 120 micrograms during the period of
      16 +/- 3 min, resulted in a moderate (< 20%), gradual decrease of the spinal
      blood flow monitored with the laser-doppler method. A subsequent injection of
      clonidine (50 micrograms) or norepinephrine (10 micrograms) resulted in a more
      pronounced decrease of spinal blood flow (35% and 79%, respectively). Three
      consecutive, daily intrathecal injections of 30 or 60 micrograms SST did not
      cause any loss of weight support or paralysis of the hind limbs. There were no
      histopathological changes in the white or gray matter of the thoracic and lumbar
      sections of the spinal cords. It is concluded that SST, in the doses studied, is
      not neurodegenerative in guinea pigs. These findings are in contrast to those
      previously seen in rats. The implication of this study may be the necessity to
      use several alternate animal species in order to evaluate the antinociceptive and
      neurodegenerative properties of the peptides administered by the intrathecal
      route and the choice of dose to be compared across species.

PMID- 1362809
TI  - Continuous spinal analgesia by means of micropumps[correction of micropumpus]: a
      report of 163 chronic pain patients.
AB  - Chronic pain in patients suffering from advanced cancer as well as unbearable
      chronic pain states depending on non-malignant pathology have always represented
      a test bench to verify results of advanced therapeutical programs as to more
      traditional approaches. The Authors present their experience resulting from
      longterm spinal infusion with peridural catheters connected to portable
      micropumps for the continuous administration of analgesic solutions. The
      availability of portable micropumps, a better understanding of spinal opioid
      receptors and advances in pharmacokinetics of opiate analgesics led in these
      years to a tremendous improvement of pain control possibilities and of the
      quality of life of patients.

PMID- 1362810
TI  - Juvenile granulosa cell tumor of an intraabdominal testis.
AB  - Juvenile granulosa cell tumor of the testis is a distinct form of sex cord
      stromal tumor of neonates and infants [1]. This tumor comprises a significant
      percentage of testicular tumors in baby boys. We present a patient who had
      preoperative imaging studies.

PMID- 1362811
TI  - [Current aspects of the pathology, diagnosis and therapy of C-cell carcinoma. A
      symposium held in Bonn, July 1991].
AB  - An essential element in the histological differentiation of medullary thyroid
      cancer (MTC) from other thyroid tumors is the use of immunohistochemical methods.
      The detection of calcitonin in the tumor cells is decisive. Factors which impair
      the prognosis of MTC are age (> 40 y), male sex, elevated DNA-content and mitotic
      activity of the tumor cells, immunoreactivity against dopa decarboxylase,
      histaminase and Leu-M1-antigen. Family screening is based mainly on calcitonin
      stimulation tests (using pentagastrin or calcium) as a genetic marker for routine
      screening is not available yet. Scintigraphic methods using 99mTc-(V)-DMSA, 201Tl
      chloride or 99mTc-anti-CEA antibodies become more important, especially in the
      detection of recurrent disease. Selective venous blood sampling is another
      sensitive method for localizing recurrent disease. Surgical treatment plays the
      dominant role in the management of MTC. Complete thyroidectomy in conjunction
      with systematic lymphadenectomy is now the primary treatment of choice.

PMID- 1362812
TI  - [The role of E. coli adhesiveness in the pathogenesis and clinical course of
      urinary tract infections].
AB  - An infection with E. coli is the most frequent cause of the urinary infections in
      childhood. Virulence depends on several factors out of which a principal role is
      played by the adhesion of bacteria to the urinary tract epithelium. Such a
      property have E. coli strains with adherence mannose-positive fimbriae of type P
      with antigens recognizing and binding glycolipid receptors on epithelial cells in
      the urinary tract. Children with such infections owe their "sensitivity+" (10% of
      the population) to genetically determined large number o receptors binding E.
      coli strains. Incidence and clinical course of the urinary tract infections have
      been analysed in the group of 184 children. Moreover, sequelae of the urinary
      tract infections with E. coli have been analysed in dependence on E. coli strain
      characteristics, i.e. presence or absence of adherent fimbriae from cases of
      cystitis and significant asymptomatic bacteriuria. Considering pathogenesis of
      the urinary tract infections as the result of interactions between bacteria and
      host, antigenic properties of adherent fimbriae might be used for preparation of
      a vaccine preventing such infections.

PMID- 1362813
TI  - 6th International Congress of Pediatric Dermatology. Toronto. Proceedings.

PMID- 1362814
TI  - Porphyrias in children.

PMID- 1362815
TI  - Calorimetric study of the interaction of local anesthetics and beta-blockers, [2
      (alkyloxy)phenyl]-2-(1-piperidinyl)ethyl esters of carbamic acid, with
      dipalmitoylphosphatidylcholine liposomes.

PMID- 1362816
TI  - Comparative variation of morphological and molecular evolution through geologic
      time: 28S ribosomal RNA versus morphology in echinoids.
AB  - The comparatively good fossil record of post-Palaeozoic echinoids allows rates of
      morphological change to be estimated over the past 260 million years and compared
      with rates of molecular evolution. Parsimony analysis of morphological data,
      based predominantly on skeletal characteristics, and parsimony, distance and
      maximum likelihood analyses of molecular data, from the first 380 bases from the
      5' end of the 28S rRNA molecule, for 10 species of echinoid produce congruent
      phylogenies. The molecular sequence chosen is demonstrably far from saturation
      and sister groups have divergence times ranging from about 15 to 260 Ma.
      Parsimony analysis allows the great majority of molecular and morphological
      apomorphies to be placed in one of 18 independent geological time intervals,
      providing a direct measure of rates of evolution for periods in the geological
      past. Because most molecular fixed point mutations in our sequences cannot be
      polarized unambiguously by outgroup comparison (making the outgroup states
      effectively random), distance and parsimony analyses both tend spuriously to root
      the echinoid tree on the longest internal branch. A topology identical to that
      derived from morphological data is, however, obtained using Maximum Likelihood
      and also parsimony analysis where outgroup rooting is restricted to more
      conserved regions. This is taken as the correct topology for assessing rates of
      evolution. Overall, both morphological and molecular changes show a moderately
      strong correlation with time elapsed, but a weaker correlation with one another.
      Statistically significant differences in evolutionary rate are found between
      some, but not all, pair-wise comparisons of sister lineages for both molecular
      and morphological data. The molecular clock rate for echinaceans is three times
      faster than that for cidaroids and irregular echinoids. Spearman's rank
      correlation test, which requires only relative magnitude of changes to be known,
      suggests that morphological change has a slightly better correlation with time
      than does molecular change, averaged over all ten species. However, when just
      echinaceans are considered an extremely good correlation is found between the
      number of molecular changes and time elapsed, whereas morphological change
      remains poorly correlated. Thus, molecular rates approximate to a clocklike model
      within restricted echinoid clades, but vary significantly between clades.
      Averaging results over all echinoids produces a correlation that is no better
      than the correlation between morphological change and time elapsed.

PMID- 1362817
TI  - To breed or not to breed: an analysis of the social and density-dependent
      constraints on the fecundity of female badgers (Meles meles).
AB  - Data from post-mortem examinations, population density estimates and long term
      capture-mark-recapture studies have been combined to look at the pattern of
      reproductive behaviour and the social factors leading to reproductive failure in
      badgers in Britain. The results are used to evaluate whether the hypothesis that
      the defence of oestrous females (as opposed to defence of food resources) best
      explains territorial behaviour and the social organization of badgers. Badgers in
      Britain have two peaks of reproductive activity, one immediately post partum and
      one in the summer/autumn. These coincide with two peaks of ovulation, and in the
      late winter/spring there is a steep rise in the number of sows carrying
      blastocysts, to reach an asymptote in June for yearling sows and April in older
      sows. Measured by their contribution to overall productivity, winter/spring
      matings were much more important than summer/autumn matings, contributing 65% of
      total autumn blastocysts in yearling sows and 71% of autumn blastocysts in older
      sows. The relative importance of the two mating periods is reflected in the
      seasonal pattern of bite wounding in adult male badgers; minor bite wounding in
      January-March was 2.3 times as frequent as in August-October, and moderate
      extensive bite wounding was 3.1 times more frequent. In the populations studied,
      pre- and post-natal losses were high, with reproductive failure occurring at all
      stages of the breeding cycle, so that less than 30% of potential productivity was
      achieved. Indeed 22% of sows failed to develop blastocysts; these had a lower
      body mass, less body fat, larger adrenal glands, poorer health and higher bite
      wound scores than sows with blastocysts. Only 44% of adult sows implanted their
      blastocysts and proceeded to the end of pregnancy. However, it was less easy to
      identify features characteristic of sows that did or did not go on to implant
      their blastocysts. Finally, 35% of sows that produced cubs ceased lactation
      early, and this loss of entire litters was thought to be due to infanticide by
      dominant sows. The presence of annexe setts correlates with increased
      productivity in younger sows, and this is thought to be because annexe setts
      enable younger sows and their cubs to avoid the aggression of older, more
      dominant sows. Living in large social groups has no net reproductive gain for
      adult males or females, and there was a decline in productivity (per adult) with
      increasing group size.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1362818
TI  - Zidovudine therapy in combination with intravenous immunoglobulin in HIV infected
      children.
AB  - There is little published data on concomitant use of zidovudine and intravenous
      immunoglobulin (IV IgG). In this paper we review our experience of four HIV-1
      infected children treated with zidovudine for periods of 19-33 months (mean 26.5
      months) subsequent to starting IV IgG for period of 18-20 months (mean 19
      months). In these children the only clear benefit we found was in one child who
      had developed HIV encephalopathy which resolved after starting zidovudine. The
      respective roles of zidovudine and intravenous immunoglobulin in HIV-1 infected
      children need to be clarified in larger comparative trials.

PMID- 1362819
TI  - Current Perspectives on the Use of Etoposide. Proceedings of a workshop. December
      5-7, 1991.

PMID- 1362820
TI  - Granulocyte-macrophage colony-stimulating factor: present status.

PMID- 1362821
TI  - The use of granulocyte-macrophage colony-stimulating factor in bone marrow
      transplantation.
AB  - GM-CSF represents an important advance in bone marrow transplantation. The drug
      can be given safely and does not appear to increase the risk of graft-versus-host
      disease or tumor relapse. This is a rare example of a new technology reducing the
      cost of health care. By shortening the duration of hospitalization, GM-CSF can
      significantly reduce the cost of a bone marrow transplant (Table 2). However,
      there are few data to support the conclusion that the reduction in the duration
      of neutropenia is associated with a superior survival. This attests to the
      excellent supportive care that has been developed for patients undergoing bone
      marrow transplantation. At present, GM-CSF has become a standard therapy in
      autologous bone marrow transplantation. However, the future will undoubtedly see
      the development of combinations of hematopoietic growth factors and/or new growth
      factors that will further improve our ability to perform bone marrow
      transplantation.

PMID- 1362822
TI  - The role of granulocyte-macrophage colony-stimulating factor-stimulated
      progenitor cells in oncology.

PMID- 1362823
TI  - [The environment, the quality and healthy style of life. The promotion of life
      and quality of life. The VI National Pastoral Meeting on Health, Fatima, December
      3, 4, 5 and 6, 1991 and Lisboa, May 4, 5 and 6, 1992].

PMID- 1362824
TI  - Gene typing of Chlamydia trachomatis by polymerase chain reaction and restriction
      endonuclease digestion.
AB  - A portion of the major outer membrane protein (MOMP) gene from 15 Chlamydia
      trachomatis serovars was amplified by polymerase chain reaction (PCR) and the
      product was analyzed by restriction fragment length polymorphism (RFLP). A set of
      primers was used to amplify an 871 base pair gene fragment encompassing the 4
      hypervariable regions of MOMP. AluI digestion of the product gave distinctive
      patterns for the 15 serovars as demonstrated on silver-stained polyacrylamide
      gels. A triple digest with EcoRI, HinfI, and HpaII allowed improved
      discrimination between closely related serovars (C, H, I, J, L3). PCR and RFLP
      were used to type 50 wild-type clinical isolates and results were compared to
      results of the solid-phase enzyme immunoassay typing method. These isolates
      represented the most prevalent genital serovars (D, E, F, K, I and J) in the
      local sexually transmitted diseases clinic population. For specimens containing 1
      serovar, the results of the two methods were similar for 42 samples and
      discordant for 1 sample. In addition, two samples showed evidence of mixed
      infection with two serovars as identified by both methods. Five additional
      specimens contained two serovars, as shown by one or both methods. In all five
      such specimens, the two typing methods agreed on at least one of the two
      serovars. For both single and multiple serovar specimens, there was concordance
      between the two typing methods for 16/17 E serovars, 8/9 D serovars, 8/8 F
      serovars, 7/7 I serovars, 7/7 J serovars, 5/8 K serovars, and 0/2 G
      serovars.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362825
TI  - [Bilateral abdominal testicles in the adult. Microsurgical and laparoscopic
      therapy].
AB  - B. L. a 27 year old bilaterally cryptorchid patient underwent right testicular
      autotransplantation in the presence of a quite normal testis. After one year the
      patency of microsurgical anastomosis was confirmed by means of Doppler flowmetry
      and scrotal echography demonstrated the presence in the scrotum of a testis
      provided will normal echogenicity. Left laparoscopic orchiectomy was planned. A
      small semilunar skin incision was made just below the rim of the umbilicus.
      Veress needle was introduced: as soon as the needle pierced the parietal
      peritoneum, its spring mechanism was released allowing the sharp needle point to
      retract leaving only the blunt tip protruding. Carbon dioxide gas was insufflated
      through the side part of the Veress needle until adequate abdominal distension
      was achieved. After having removed the Veress needle, the laparoscope on its
      sharp-pointed trocar was introduced into the peritoneal cavity and left testis
      was easily localized. Four trocars were introduced up to proceed to laparoscopic
      orchiectomy. The patient was discharged two days after. In our opinion in the
      presence of a bilateral cryptorchism in the adult, is better to plan a
      monolateral autotransplantation. After having verified the long-term result of
      microsurgery we can decide if a contralateral orchiectomy has to be planned.

PMID- 1362827
TI  - Population analysis of single neurons in cat somatosensory cortex.
AB  - Single neurons in the somatosensory cortex are divisible into a population with
      receptive fields and a population without receptive fields. These two populations
      display different laminar distributions, and their respective functions are
      unknown. We compared other physiological characteristics of these two neuronal
      populations in an attempt to understand why some neurons lack a receptive field.
      Only 23% of 465 neurons isolated in the somatosensory cortex of halothane
      anesthetized cats displayed a cutaneous receptive field. The iontophoretic
      administration of glutamate uncovered input from the periphery in another 34% of
      the sample, leaving 43% of the neurons without evidence of peripheral input under
      these experimental conditions. Neurons with a receptive field were spontaneously
      active much more often than neurons lacking peripheral inputs, and their rates of
      discharge were higher. No differences were found between neurons having a
      receptive field uncovered with glutamate and those unaffected by glutamate. In
      all classes of neurons, those cells with spontaneous activity were excited by
      smaller amounts of glutamate than were silent neurons, but sensitivity to
      glutamate was not correlated with the presence or absence of a receptive field.
      We infer that some classes of somatosensory cortical neurons receive strong
      thalamocortical inputs, whereas others have only relatively weak or no
      thalamocortical connections. In other experiments we have shown also that those
      neurons lacking a receptive field and/or spontaneous activity were more likely to
      be plastic than those with stronger inputs (see Warren and Dykes, 1993a,b),
      suggesting that neurons having weaker afferent inputs can be more readily
      modified under certain circumstances.

PMID- 1362826
TI  - Genetic variation in pathogenic bacteria.
AB  - In contrast to textbook ideas of pure cultures and defined strains, genetic
      variation is a fact of life in the microbial world. It not only allows pathogens
      to establish themselves in their chosen host, but also allows them to resist that
      host's subsequent attempts to evict them. Here we review some of the mechanisms
      that bring about this variation, and some of the functional consequences that
      result from it.

PMID- 1362828
TI  - Secretion of urokinase and tissue-plasminogen activator by epidermal cells in the
      presence of psoriatic fibroblast-conditioned medium.
AB  - The present study examined secretion of urokinase and tissue-plasminogen
      activator by epidermal cells in the presence of psoriatic or uninvolved skin
      fibroblast-conditioned medium. Using zymographic analyses, a 54kD lysis band and
      a small 110kD band derived from urokinase could be detected in the harvest fluid
      from keratinocytes treated with both psoriatic and uninvolved fibroblast
      conditioned medium, as well as very weak lysis bands of 63kD and 120kD derived
      from tissue-plasminogen activator in the harvest fluid treated with psoriatic
      fibroblast-conditioned medium, but not with uninvolved fibroblast-conditioned
      medium.

PMID- 1362829
TI  - The hairless mouse model for assaying the atrophogenicity of topical
      corticosteroids.
AB  - The daily application of corticosteroids for 18 days to the dorsal skin of
      hairless mice resulted in loss of volume of all the cutaneous compartments. The
      epidermis thinned, sebaceous glands regressed, dermal thickness was reduced, horn
      filled cysts shrunk, subcutaneous fat disappeared, and regression of the muscular
      layer occurred. The magnitude of these changes correlated strongly with the
      accepted potency ranking of these agents by clinical efficacy. Thus,
      atrophogenicity predicts anti-inflammatory activity. This model furnishes a
      simple screening method for assaying corticosteroid activity and for optimizing
      proprietary formulations.

PMID- 1362830
TI  - Expression of loricrin in skin disorders.
AB  - Loricrin, the major component of the cornified envelope, is normally expressed in
      the granular layer of epidermis during the last steps of keratinocyte
      differentiation. Using an antiloricrin antiserum (A8-73), an increased expression
      of this envelope precursor was found in some disorders of hyperorthokeratosis
      (ichthyosiform erythroderma; lichen ruber), but not in others (keratodermia
      ichthyosis vulgaris). In disorders accompanied by parakeratosis, a sign of
      incomplete differentiation (psoriasis, prurigo nodularis) loricrin was not
      detected, whereas the tissue expressed filaggrin. Treatment of normal skin with
      retinoic acid, increasing epidermal thickness in some subjects, led to an
      increased expression of loricrin. Loricrin might be a useful indicator of the
      extent of terminal epidermal differentiation in skin disorders.

PMID- 1362831
TI  - Adenosine deaminase activity in sera of patients with psoriasis, mycosis
      fungoides and adult T cell leukemia.
AB  - Adenosine deaminase activities in sera were measured in 18 psoriatic patients, 8
      mycosis fungoides patients, and 9 patients with adult T cell leukemia. Adenosine
      deaminase activity in the sera of the psoriatic patients showed no significant
      increase. An elevated adenosine deaminase activity was observed in 7 of the 8
      patients with mycosis fungoides and 8 of the 9 patients with adult T cell
      leukemia. After chemotherapy, adenosine deaminase activity in serum of acute
      adult T cell leukemia was reduced. Adenosine deaminase activity in the sera of 2
      patients with smoldering adult T cell leukemia was more elevated, with
      exacerbation of the disease. It is difficult to grade the extension of the tumors
      in plaque stage mycosis fungoides and smoldering adult T cell leukemia. To know
      the progression of the disease is critical in determining its management. These
      results indicate that adenosine deaminase activity in serum is one of the
      reliable indicators for the grading of mycosis fungoides and adult T cell
      leukemia.

PMID- 1362832
TI  - Localized proliferative effect of preadipocytes on cultured human epidermal
      keratinocytes.
AB  - The effect of preadipocytes (ST 13) on cultured normal human epidermal
      keratinocytes (NHEK) was investigated. The growth of NHEK was accelerated with co
      cultured ST 13 cells. This stimulative effect must have been localized around
      viable ST 13 cells, because neither the medium nor the surface conditioned by ST
      13 or the ST 13 cell fragments showed any promotion of NHEK growth, and NHEK
      showed a compact, paving-like arrangement only when they were attached directly
      to ST 13 cells. It became clear that these compactly arranged keratinocytes have
      an active proliferative ability, since their nuclei showed a marked uptake of 5
      bromodeoxyuridine (BrdU) and they were positively stained with anticytokeratin
      37, a monoclonal antibody against the basal epidermis. Under electron microscopy,
      ST 13 preadipocytes were closely connected with NHEK. These results, together
      with those of previous reports, suggest that the localized proliferative effect
      of ST 13 cells on NHEK is due to cell-to-cell contact.

PMID- 1362833
TI  - Lifetime topical application of tretinoin to hairless mice.
AB  - The discovery that topical tretinoin can reverse some of the effects of
      photodamage may lead to its chronic application. Examination of long-term effects
      was of interest. Three groups of hairless mice (age 6-8 weeks) were treated
      dorsally with 1) tretinoin (0.025%), 2) cream vehicle, 3) sham treatment.
      Applications were 3 times weekly and continued for up to 2 years until all mice
      were sacrificed or had died. Biweekly examinations showed no sign of retinoid
      toxicity, with growth and longevity similar in all groups. Tretinoin-treated skin
      was smooth and pink, resembling that of younger mice. Controls had yellowed,
      irregularly thickened skin. Histologically, tretinoin-treated skin had a
      hyperplastic epidermis consisting of plump, cytologically normal cells. Control
      skin had 3-4 compressed cell layers. Foci of new normally staining collagen were
      present in the subepidermal dermis of tretinoin-treated skin; fibroblasts were
      large and abundant in these areas. These foci were absent in controls. Mice
      treated with tretinoin also appeared to have increased amounts of elastic fibers
      and glycosaminoglycans.

PMID- 1362834
TI  - Elemental changes in guinea pig epidermis at repeated exposure to sodium lauryl
      sulfate.
AB  - Epidermal hyperplasia is the response of the epidermis to external harmful
      stimuli. The control and regulation of this hyperplasia is not completely
      understood. It has been proposed that changes in the cellular sodium/potassium
      ratio are of importance in the regulation of cell proliferation. To evaluate if
      such a change in the elemental content of epidermal cells can be one factor to
      consider at irritant contact dermatitis, we performed a quantitative assessment
      of sodium lauryl sulfate (SLS)-induced contact reactions in the guinea pig. SLS
      was applied 1, 2 or 3 times and biopsies were obtained at 24 and 84 h after the
      last application. It was found that repeated exposures to SLS induced a
      hyperplasia of epidermis at 24 h persisting at 84 h. At 24 h there were
      significant changes in the sodium and potassium content of the keratinocytes. At
      84 h there was still an increased potassium level in the cells and the
      sodium/potassium ratio was significantly decreased in epidermis exposed three
      times to SLS. This implies that changes in cellular sodium/potassium ratios occur
      in epidermal hyperplasia following irritant stimuli.

PMID- 1362835
TI  - A dose-response study of irritant reactions to sodium lauryl sulphate in patients
      with seborrhoeic dermatitis and atopic eczema.
AB  - The susceptibility of the skin of patients with seborrhoeic dermatitis to
      surfactant irritation was investigated and compared to that of a group of normal
      subjects and patients with a history of atopic eczema. Responses to six
      concentrations of sodium lauryl sulphate (SLS), applied to forearm skin, were
      assessed clinically and measured by laser Doppler flowmetry. Analysis of dose
      response curves showed statistically significant increased susceptibility to SLS
      induced irritation in patients with seborrhoeic dermatitis and atopic eczema
      compared with normal subjects. Increased susceptibility to chemical irritation
      may be important in the pathogenesis of seborrhoeic dermatitis.

PMID- 1362836
TI  - Cyclosporin A responsive chronic severe vesicular hand eczema.
AB  - A patient with an otherwise recalcitrant chronic vesicular hand eczema responded
      with a dramatical improvement within 2 weeks of cyclosporin A (CsA) therapy 5.0
      mg/kg daily. The patient was still free of eczema in spite of reducing the CsA
      dose to 2.5 mg/kg daily. CsA therapy was finally stopped due to a moderate
      increase in blood pressure, resulting in rapid recurrence of the hand eczema. The
      case report clearly demonstrates that oral CsA should be considered in patients
      with severe hand eczema that cannot be controlled on conventional
      immunosuppressive treatments.

PMID- 1362837
TI  - Folinic acid rescue used routinely in psoriatic patients with known methotrexate
      "sensitivity".
AB  - Many combinations of methotrexate and folic or folinic acid have been used to
      limit the side effects of methotrexate therapy in psoriasis or psoriatic
      arthropathy. Methotrexate inhibits the enzyme dihydrofolate reductase and
      prevents the formation of DNA and RNA. Folinic acid, the 5-formyl derivative of
      tetrahydrofolic acid, is the active form of folic acid. We have confirmed in 5
      patients that continuous administration of folinic acid with weekly oral
      methotrexate prevents improvement of psoriasis. When folinic acid was ceased on
      the day of methotrexate in these patients their psoriasis improved. Five other
      patients with previous sensitivity to methotrexate, forcing cessation of therapy,
      were given weekly oral methotrexate and folinic acid every day except the day of
      methotrexate. Marked improvement of psoriasis or arthropathy occurred in each
      case without side effects. This method precisely limits the exposure to
      methotrexate, allowing a therapeutic effect without complication even in those
      patients who exhibit methotrexate sensitivity.

PMID- 1362838
TI  - Intertriginous drug eruption.
AB  - Presented are two patients who developed an unusual, and as yet unreported
      eruption due to amoxycillin. They exhibited an eruption confined to the
      intertriginous areas, which mimicked intertrigo. Although drug eruption can mimic
      a variety of idiopathic skin diseases, intertrigo is easily distinguished from
      drug eruption and has not been mentioned in the differential diagnosis of this
      reaction. It is suggested that drug reactions should be considered in the
      differential diagnosis of intertrigo, in particular of atypical and therapy
      resistant cases. Early detection of these cases has practical importance since
      the elimination of the causative drug is essential for therapy success. Case 2
      showed a response of the toxic epidermal neurolysis (TEN) type, which could have
      been very severe and dangerous had the diagnosis not been made in an early stage
      before the development of generalized TEN.

PMID- 1362839
TI  - Juvenile generalized pustular psoriasis in a pair of monozygotic twins presenting
      strikingly similar clinical courses.
AB  - We describe an exceptionally rare case of juvenile generalized pustular psoriasis
      noted in monozygotic twins who, after developing the disease on the same day (the
      48th day after birth) continued to show strikingly similar clinical features of
      generalized pustular psoriasis for 7 years. Not even therapeutic intervention by
      tonsillectomy performed at age 4 years on one of the twins, which was expected to
      have some beneficial effect, could decrease the number of attacks or pustulation
      compared with the counterpart.

PMID- 1362840
TI  - Efficacy and skeletal side effects of two years' acitretin treatment.
AB  - In this prospective study, 51 patients suffering from psoriasis and ichthyosis
      were treated with acitretin for 2 years. The average dose was 0.5 mg/kg/day. We
      have evaluated the efficacy and side effects, focusing on skeletal side effects.
      X-ray examinations were done before treatment and after 1 and 2 years. Forty-five
      patients completed the study. Acitretin had a good clinical effect, with 75%
      improvement in 35 of the patients. Apart from the well-known side effects
      affecting the mucous membranes, one patient developed biopsy- proven toxic
      hepatitis. In 2 patients we observed unusual skeletal calcifications located in
      the forearms and in the hip. These were considered to be caused by the drug. In
      this study, which included patients up to 71 years, only radiographs of the
      pelvis and the forearms were of value as routine follow-up films.

PMID- 1362841
TI  - One-minute dithranol therapy in psoriasis: a placebo-controlled paired
      comparative study.
AB  - In a double-blind left-right randomised comparison, 27 patients suffering from
      chronic plaque-type psoriasis vulgaris were treated for one minute with dithranol
      2% ointment, Psoralon (Psoralon MT), on a selected psoriasis plaque on one half
      of the body and with a placebo ointment on a corresponding plaque on the other.
      The preparations were applied once daily for 8 weeks. Seventeen patients achieved
      clearing or considerable improvement with dithranol therapy, as compared with 6
      patients with placebo (p = 0.002). Erythema, infiltration, scaling, pruritus and
      the overall result were assessed. Statistically significant differences in favour
      of dithranol treatment were seen for all five variables, except for pruritus. The
      average of these five variables, designated the mean score, was also analysed;
      dithranol was seen to yield significantly better results (p = 0.001). Staining of
      clothes and the bathroom was noted by 3 and 5 patients, respectively, but no
      medical side effects were seen.

PMID- 1362842
TI  - Aberrant cutaneous weal and flare responses in chronic urticaria.
AB  - This study examined cutaneous mast cell behaviour in 14 patients with chronic
      urticaria but no dermographism and 11 healthy controls, by measuring cutaneous
      weal and flare reactions evoked in response to intradermal challenge injections
      of 0.1 ml isotonic saline, histamine (20 micrograms), codeine phosphate (10
      micrograms) and compound 48/80 (10 micrograms). Five minutes after each
      injection, the area of the resulting weal and flare was calculated by computer
      aided planimetry. The process was repeated at 15, 30 and 45 min following the
      injection. In patients, saline flares were significantly larger than those of the
      volunteers at 15, 30 and 45 min (p < 0.05). However, histamine and codeine flare
      areas were significantly smaller in the patients when compared to the controls at
      15, 30 and 45 min (p < 0.05). Compound 48/80 produced smaller reactions in the
      patients without reaching statistical significance.

PMID- 1362843
TI  - Treatment with bifonazole shampoo for seborrhea and seborrheic dermatitis: a
      randomized, double-blind study.
AB  - Forty-four patients with seborrhea and seborrheic dermatitis of the scalp were
      treated with either bifonazole shampoo (22 patients) or the vehicle shampoo (22
      patients) in a randomized, double-blind vehicle-controlled study. The patients
      were instructed to wash their scalps 3 times weekly for 6 weeks and were examined
      every 3 weeks. Responses were evaluated by clinicians using a clinical grading of
      scaling, erythema and overall improvement, and also by the patients, who assessed
      pruritus and overall improvement, using a scale of 0 to 3. The improvement
      following the bifonazole shampoo was found to be significantly greater than that
      achieved with the vehicle shampoo in regard to the clinical evaluation of scaling
      (p = 0.01) as well as patient evaluation of pruritus (p = 0.008) and overall
      improvement (p = 0.03). No major adverse side effects were recorded.

PMID- 1362844
TI  - Allergic contact sensitization in an unselected Danish population. The Glostrup
      Allergy Study, Denmark.
AB  - The distribution of allergic contact sensitization was assessed in an unselected
      population, living in western Copenhagen, Denmark. Ready-to-apply patch tests
      comprising 23 haptens and mixtures of haptens were mailed to 793 adults, and 567
      (71.5%) participated. The tests were read 2 days after application. A total of
      111 positive reactions were found among 86 (15.2%) subjects. Sensitization was
      less frequent in men than in women (11.5% versus 18.8%). Twenty out of the 23
      chemicals in the test elicited positive reactions. Positive reactions to nickel
      and thiomersal were found most frequently (6.7% and 3.4%, respectively).
      Concerning the other chemicals the frequencies were 1.1% or less. Nickel
      sensitivity was less frequent in men than in women (2.2% versus 11.1%). The
      frequencies of sensitization probably represent minimum figures. Regulation of
      exposure needs to be considered in order to prevent primary sensitization and
      disease recurrences in those already sensitized.

PMID- 1362845
TI  - Intractable chronic furunculosis: prevention of recurrences with pentoxifylline.
AB  - A 60-year-old HIV-negative man with known noninsulin-dependent diabetes mellitus
      and glucose 6-phosphate-dehydrogenase deficiency anemia suffered from chronic
      recurrent furunculosis since the age of 30. In recent years, his condition had
      become increasingly severe and the recurrences increasingly frequent. Different
      measures including continuous therapy with large doses of systemic antibiotics
      for a period of 6 months failed to prevent the recurrences. Oral treatment with
      pentoxifylline 400 mg t.i.d. was prescribed, and 2 months later the patient
      experienced a dramatic and complete remission of his furunculosis. Six months
      later he was still totally free of lesions while continuing to take the same
      medication. Pentoxifylline may provide a new and effective approach to the
      previously difficult and often disappointing problem of the management of
      patients with chronic recurrent furunculosis.

PMID- 1362846
TI  - Treatment of prurigo nodularis, chronic prurigo and neurodermatitis circumscripta
      with topical capsaicin.

PMID- 1362847
TI  - The "red face"--a warning sign of malignant melanoma?

PMID- 1362848
TI  - Cholinergic modulation of GH secretion in acromegalic patients before and after
      pituitary surgery.
AB  - Cholinergic neurotransmission exerts a physiological control on GH secretion.
      Pirenzepine (Pz), an antagonist of muscarinic receptors, by enhancing
      hypothalamic somatostatin release, inhibits stimulated GH secretion in normal
      subjects but not in acromegalic patients. To address the hypothesis that a
      feedback effect of GH hypersecretion can be involved in this condition, GH
      responses to GHRH 1-29, 1 microgram/kg iv, with and without administration of Pz,
      40 mg iv before tests, were investigated in eight acromegalic patients, before
      and 20-30 days after transsphenoidal adenomectomy. Pz diminished (p < 0.001) the
      incremental area under the curve (AUC) of GH responses to GHRH in seven normal
      controls. In contrast, GHRH responsiveness in untreated acromegalic patients was
      not affected by Pz. Postoperative basal GH levels decreased by 62.4 +/- 14.9% (p
      < 0.01). Pz inhibited GH responses to GHRH (p < 0.01). Furthermore, a direct
      relationship (r = 0.73, p < 0.01) between basal concentrations and the AUC of GH
      responses following Pz plus GHRH-test was found. The finding that muscarinic
      receptor activity recovered after the reduction of serum GH basal levels by
      pituitary surgery lends support to the proposed pathophysiological role of GH
      excess as a possible determinant factor in cholinergic-somatostatinergic
      dysfunction in acromegaly.

PMID- 1362849
TI  - Effect of insulin-like growth factor I on the thyroid axis in patients with Laron
      type dwarfism and healthy subjects.
AB  - We have evaluated the effect of exogenous administration of IGF-I on the thyroid
      axis in four separate studies: (1) iv bolus injection; (2) single sc injection;
      (3) seven days' sc treatment, and (4) four months' treatment. Thirteen patients
      with Laron-type dwarfism (LTD) participated in the investigations. In studies 1
      and 2, 10 healthy subjects were also included. Before and during long-term
      treatment (study 4) six LTD patients underwent a TRH test. IGF-I was administered
      in a dose of 75 micrograms.kg-1 iv or 120-150 micrograms.kg-1 sc. Single
      injections of IGF-I caused significant decreases of serum TSH in LTD patients
      (iv: 1.7 +/- 0.2 to 1.1 +/- 0.1 mU/l; sc: from 2.1 +/- 0.4 to 1.1 +/- 0.2; p <
      0.0005). In controls the decrease was for iv from 1.2 +/- 0.2 to 0.8 +/- 0.2 mU/l
      (p < 0.02) and for sc from 2.0 +/- 0.5 to 0.8 +/- 0.2 mU/l (p < 0.05). Long-term
      administration of IGF-I induces a transitory decrease of both serum TSH and fT4,
      followed by a spontaneous rise to pretreatment or even higher values. No changes
      in T3 were observed. TSH stimulation by TRH was significantly augmented after
      four months of IGF-I treatment (p < 0.005). The effects of IGF-I can be explained
      by an early stimulation of somatostatin release causing a decrease in TSH and
      followed by the development of compensatory mechanisms. All changes were within
      the normal ranges, not causing abnormal thyroid function.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1362851
TI  - [2-chlorodeoxyadenosine (2-CDA)--a new antineoplastic and immunosuppressive
      drug].

PMID- 1362850
TI  - Growth hormone secretion in old female rats analyzed by the reverse hemolytic
      plaque assay.
AB  - Growth hormone (GH) release was studied in young (3-4-month-old) and old
      persistent diestrous (20-21-month-old) female rats using the reverse hemolytic
      plaque assay. A bimodal distribution of reverse hemolytic plaque area was
      observed in both young and old female rats. The mean and median of the plaque
      area of GH cells from old females were smaller than those from young female rats.
      The percentage of plaque-forming GH cells in old female rats was lower than in
      young female rats. The percentage of large plaque-forming GH cells (plaque area,
      more than 8 x 10(3) microns2) was lower in old female rats than in young female
      rats. GH-releasing hormone (GHRH) increased the mean and median of plaque areas
      in both young and old female rats. However, responsiveness to GHRH was reduced in
      old female rats. These results indicate that the amount of GH released from
      individual GH cells decreases with age in female rats, resulting in diminished GH
      secretion.

PMID- 1362852
TI  - [Autologous blood-derived stem cell transplantation in the treatment of
      proliferative disorders of the hematopoietic system (I)].
AB  - Peripheral blood can be an alternative source of hematopoietic stem cells which
      after autografting are capable of sustaining or completely recovering of
      lymphopoiesis without the necessity of bone marrow harvesting. Theoretical
      assumptions conditioning the clinical application of circulating stem cells
      autotransplantation have been described. The results of experimental studies
      performed in animals and humans have allowed for closer characterization of these
      cells. However, the physiological significance of their presence in the
      peripheral blood still remains unknown.

PMID- 1362853
TI  - The role of purinergic neurotransmission in various cardiovascular reflexes.
AB  - In urethane-anaesthetized rats the effects of alpha-adrenoceptor antagonists and
      desensitization of P2-purinoceptors with alpha,beta-methylene ATP on the pressor
      reflex responses were investigated. Pressor responses were elicited by electrical
      stimulation of the central end of the sciatic nerve, by asphyxia and by occlusion
      of the common carotid artery. Responses to sciatic nerve stimulation and to
      asphyxia, but not those to carotid artery occlusion were entirely suppressed by
      dihydroergotamine and phentolamine. Under the action of dihydroergotamine the
      sinocarotid reflex decreased by over 70% in 40% of the experiments. In 60% of
      experiments the response was only slightly reduced or even augmented, but it was
      entirely inhibited by subsequent desensitization with alpha,beta-methylene ATP.
      The magnitude of response to sciatic nerve stimulation was almost unaffected by
      alpha,beta-methylene ATP, while the response to carotid occlusion was decreased
      by 40-50%. The recovery of purinoceptor sensitivity to alpha,beta-methylene ATP
      was accompanied by restoration of the sinocarotid reflex. It is suggested that
      purinergic neurotransmission plays a considerable role in the pressor sinocarotid
      reflex, while in the pressor response to stimulation of somatic afferents its
      role is negligible.

PMID- 1362854
TI  - Modulation of G proteins and second messenger responsiveness by steroid hormones
      in GH3 rat pituitary tumour cells.
AB  - We have investigated the modulation of different G protein alpha- and beta
      subunit levels in prolactin (PRL) and growth hormone producing rat pituitary
      adenoma cells (GH3 cells) in culture after prolonged exposure (6-48 h) to the
      steroid hormones 17 beta-oestradiol and dexamethasone. Gi-3 alpha- and G beta
      subunits were the only G protein subunits which increased in response to 10(-6) M
      oestradiol (to approximately 150 and 200% of controls, respectively), while the
      other alpha-subunits investigated (Gs alpha, Gi-2 alpha and G(o) alpha) remained
      relatively unchanged. Thyroliberin (TRH)--and guanosine 5'-[beta gamma
      imido]trisphosphate (Gpp(NH)p)-elicited adenylyl cyclase (AC) activities were
      reduced during 6-12 h of oestradiol treatment (by 60 and 20%, respectively),
      while the inhibitory effect of somatostatin (SRIF) increased by approximately
      100%. Dexamethasone (10(-6) M) increased levels of the stimulatory G protein Gs
      alpha (to approximately 340%) and decreased levels of Gi-3 alpha (to 25%). After
      48 h, the AC response to TRH was reduced by approximately 70%, whereas the effect
      of the other modulators remained close to controls. We conclude that G protein
      subunits in GH3 cells are subject to specific regulation by steroid hormones and
      that this may be important in the tuning of the responsiveness of PRL secretion
      to hormones in the in vivo situation.

PMID- 1362855
TI  - The influence of moderate hypothermia on cellular calcium uptake in complete
      ischaemia: implications for the excitotoxic hypothesis.

PMID- 1362856
TI  - Activation of phosphoinositide turnover and protein kinase C by neurotransmitters
      that modulate calcium channels in embryonic chick sensory neurons.
AB  - Gamma aminobutyric acid (GABA) and norepinephrine modulate the excitability of
      primary chick sensory neurons by decreasing the voltage dependent Ca current.
      Although previous electrophysiological studies indicate that neurotransmitter
      modulation of the Ca current in these neurons involves protein kinase C, the
      biochemical aspects of this mechanism have not been examined directly. We find
      that both norepinephrine (via a unique alpha receptor subtype) and GABA (via
      GABAb receptors) linked to pertussis toxin sensitive pathways, stimulate the
      metabolism of membrane phosphatidylinositol phospholipids in primary chick
      sensory neurons. In addition, norepinephrine causes the rapid translocation of C
      kinase activity from cytosolic to membrane associated distribution, consistent
      with its rapid activation in response to applied neurotransmitter. The
      pharmacology, pertussis toxin sensitivity and time course of the biochemical
      changes due to neurotransmitter treatment parallel the effects of these
      transmitters on calcium current modulation. These biochemical studies confirm the
      hypothesis that activation of protein kinase C is critically involved in calcium
      channel modulation in embryonic chick sensory neurons.

PMID- 1362858
TI  - Prostate Cancer and Bone Metastasis. Proceedings of a conference. Gotenba, Japan,
      December 12, 1990.

PMID- 1362857
TI  - Neurochemical changes of long-term adrenalectomy in rat brain: effects on
      neurotransmitter amino acids.
AB  - The levels of five amino acids together with glutamine synthetase activity, were
      measured in brain regions of rats with bilateral adrenalectomy, performed in
      newly weaning rats on postnatal day 22 and sacrificed 3 months later.
      Adrenalectomy caused a general decrease of glutamine concentration in three
      hippocampal regions (CA1-CA2, CA3, CA4-dentate gyrus), in hypothalamus, striatum
      and cerebellum. This reduction, which was particularly significant in hippocampus
      and cerebellum, was paralleled by a decrease of glutamine synthetase activity.
      Treatment with corticosterone reversed the effect of adrenalectomy. Little or no
      change was observed in the tissue levels of taurine, aspartic, glutamic or gamma
      amino butyric acids.

PMID- 1362859
TI  - Extensive polymorphism of the BoLA-DRB3 gene distinguished by PCR-RFLP.
AB  - A polymerase chain reaction (PCR)-based method is described for typing of alleles
      of the bovine lymphocyte antigen (BoLA)-DRB3 gene. A total of 30 DRB3 alleles
      were distinguished by digestion of PCR amplification products of BoLA-DRB3 exon 2
      with RsaI, BstYI and HaeIII (PCR-RFLP). All restriction fragment patterns, with
      the exception of one HaeIII pattern, were consistent with restriction sites that
      were found among 14 previously sequenced DRB3 alleles. The PCR-RFLP typing method
      was evaluated on 168 genomic DNA samples collected from animals of 10 cattle
      breeds, 48 of which were typed in the Fourth International BoLA Workshop for BoLA
      DRB and -DQ by conventional restriction fragment length polymorphism (RFLP)
      analysis using heterologous and homologous DNA probes. Thirty-one DRB/DQ
      haplotypes containing 23 DRB3 alleles were identified among the 48 workshop
      animals analysed. Using PCR-RFLP, 11 DRB3 alleles were identified in 18 workshop
      animals for which DRB RFLPs were not informative. PCR-RFLP typing of additional
      animals revealed five new DRB3 alleles, of which three contained a putatively
      located three basepair deletion in the identical position as found for the
      sequenced allele DRB*2A. PCR-RFLP was shown to be a rapid and sensitive method
      for the detection of polymorphism in a functionally relevant domain of the BoLA
      DRB3 gene and should be useful for studying the evolution of DRB polymorphism in
      cattle and other Bovidae.

PMID- 1362860
TI  - Isolation and sequencing of porcine lipoprotein lipase cDNA and its use in
      multiallelic restriction fragment length polymorphism detection.
AB  - Porcine lipoprotein lipase (LPL) cDNA has been cloned and sequenced. The deduced
      amino acid sequence shows a high degree of identity to LPL from other species,
      and contains the Ser/His/Asp triade characteristic of serine proteases and
      esterases. A repetitive element is present in the 3'-untranslated region of the
      cDNA. A partial cDNA covering the coding region of LPL detects three restriction
      fragment length polymorphisms with HindIII. This represents the first marker
      assigned to porcine chromosome 14.

PMID- 1362861
TI  - Diagnosis of bovine freemartinism by the polymerase chain reaction method.

PMID- 1362863
TI  - A BamHI RFLP at the locus encoding the 65-kDa regulatory subunit of porcine
      protein phosphatase 2A (PPP2ARB).

PMID- 1362862
TI  - A TaqI RFLP at the porcine thyroid stimulating hormone beta-subunit locus (TSHB).

PMID- 1362865
TI  - RFLP at the bovine phosphogluconate dehydrogenase (PGD) locus.

PMID- 1362864
TI  - RFLPs at the ovine locus for growth hormone.

PMID- 1362866
TI  - RFLP at the bovine Gardner-Rasheed feline sarcoma oncogene homologue (FGR) locus.

PMID- 1362867
TI  - RFLP at the bovine liver, bone and kidney alkaline phosphatase (ALPL) locus.

PMID- 1362868
TI  - [Endocrine sequelae of oncologic pathology. Historic evolution].

PMID- 1362869
TI  - [XIV Congress of the Pediatric Endocrinology Section of the Spanish Association
      of Pediatrics. Madrid, 7-9 May 1992].

PMID- 1362870
TI  - Regional localization of the intestinal mucin gene MUC3 to chromosome 7q22.
AB  - The gene MUC3 which codes for a mucin expressed in intestine (Gum et al. 1990)
      has previously been mapped, using somatic cell hybrids, to chromosome 7. We
      describe here the regional localization of MUC3 to chromosome 7q22 by in situ
      hybridization. Preliminary linkage analysis using CEPH (Centre d'Etude du
      Polymorphisme Humain) families supports this assignment and places MUC3 in the
      same linkage group as COL1A2 and CFTR.

PMID- 1362871
TI  - A Y-associated allele may be characteristic of certain ethnic groups in Asia.
AB  - The probe 47z detects DNA polymorphisms on both the X and Y chromosomes. Blood
      samples were collected from Korean, Chinese, Jewish, Caucasian and Negro
      populations and polymorphisms of both loci were compared with findings previously
      reported in Japanese. Both Y1 and Y2 alleles were detected in Japanese and
      Koreans. However, only the Y1 allele was detected in each of the other
      populations. Although, both X1 and X2 alleles were detected in all examined
      populations, the frequency of the X2 allele was very low among Negroes.

PMID- 1362872
TI  - Mitochondrial DNA polymorphisms in Khoisan populations from southern Africa.
AB  - Mitochondrial DNA (mtDNA) restriction fragment length polymorphisms (RFLPs) were
      investigated in 95 individuals, consisting of 49 San ('Bushmen') and 46 Nama
      ('Hottentot') individuals from Namibia, using the restriction enzymes HpaI,
      BamHI, HaeII, MspI, AvaII and HincII. Six of the eleven types found in the pooled
      Khoisan sample are shared, albeit at varying frequencies, suggesting that both
      the San and Nama have evolved from a recent common ancestor. However, San and
      Nama groups differ appreciably, in particular, type 3-2 (3-1-1-2-2-2) was found
      in 7/49 Sekele and 25/46 Nama (chi 2 [1] = 15.3, P = 9.17 x 10(-5)). In addition,
      type 4 makes up 42.8% of the types found in the San, and is not found in the Nama
      group. This suggests that the San and Nama have evolved along separate lineages,
      with little gene flow between them, following their proposed separation from a
      common Khoisan ancestor. Type 7-2 (3-1-1-1-1-2), most common in Negroid
      populations, is found at a higher frequency in the San (20.4%) than the Nama
      (6.5%), suggesting that miscegenation involving Negroid females and San males is
      more common than that between Negroid females and Nama men. The higher frequency
      of type 21-2 (2-1-1-1-2-2) in the Nama (13%) than in the San (4.1%), may be
      attributable to gene flow from the Dama into the Nama, consistent with the
      consequences of enslavement of the Dama by the Nama.

PMID- 1362873
TI  - A sero-epidemiological study on mother-to-child transmission of HTLV-I in
      southern Kyushu, Japan.
AB  - In vertical transmission of HTLV-I the duration of breast-feeding seems to be an
      important risk factor. In this study, we made prospective and retrospective
      surveys on the rate of vertical transmission of HTLV-I in infants and their
      siblings born to HTLV-I seropositive mothers. The results obtained were as
      follows. (1) In the prospective study, 885 of the 16,283 pregnant women examined
      were HTLV-I seropositive, and the seropositive rate was 5.4%. The seroconversion
      rates of short-term (< 7 months) and long-term (> or = 7 months) breast-feeders
      were 3.8% (1/26 cases) and 25.0% (1/4 cases) respectively, and the rate of bottle
      feeders was 5.6% (10/177 cases). Short-term breast-feeding tended to yield a
      lower seroconversion rate of infants. In addition, the seroconversion rate of
      short-term breast-feeders was nearly equal to that of bottle-feeders: 3.8% vs.
      5.6%. (2) In the retrospective study, the seroconversion rates of short-term and
      long-term breast-feeders in their siblings were 4.5% (3/67 cases) and 14.0%
      (19/136 cases) respectively. There was a significant difference between the 2
      groups (p < 0.01). Thus, the results of our retrospective and prospective studies
      suggest that short-term breast-feeding might lessen the risk of breast-milk-borne
      transmission of HTLV-I from carrier mothers to their children.

PMID- 1362874
TI  - Possible mechanisms of activation of soluble guanylate cyclase by organic
      nitrates.
AB  - Various possible mechanisms for the activation of soluble guanylate cyclase by
      the organic nitrates are discussed. It is suggested that the mechanisms in intact
      blood vessels and in blood vessel homogenates are probably different.

PMID- 1362875
TI  - Molecular basis of discrepancies in neurotoxic properties among 1-methyl-4-aryl
      1,2,3,6-tetrahydropyridines.
AB  - The relationship between structural specificity of the main stages of 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) action and the display of
      parkinsonogenic properties among homologous structures in a number of 4-tolyl
      derivatives of MPTP has been studied. All the compounds are better substrates for
      monoamine oxidase (MAO) than MPTP. MAO is inactivated during the reaction
      according to a mechanism of irreversible inhibition by 2,3-dihydropyridinium
      metabolite. All the tolyl derivatives are stronger inhibitors of MAO than 1
      methyl-2,3-dihydropyridinium (MPDP). A significant contribution of enzyme
      inhibition to the catalytic conversion of the substrate leads to the fact that
      substrates having equal (para isomer) or even higher (meta isomer) values of
      catalytic parameters are oxidized by MAO to a lesser extent than MPTP. It has
      been found that all 4-arylpyridiniums (final products of MATP bioconversion)
      competitively and reversibly inhibit [14C]dopamine (DA) uptake in mouse brain
      synaptosomes. Affinity toward DA transporter characterized by KI (microM) is 0.37
      +/- 0.04, 0.7 +/- 0.1, 2.0 +/- 0.15, 2.0 +/- 0.35 for MPP, and its o-, m-, and p
      tolyl derivatives, respectively. Joint calculation of specificity factors for the
      processes discussed define the following rank order for the bio-delivery of
      MATP's metabolic produces into DA nerve terminals: o-tolyl > MPTP >> m-tolyl > p
      tolyl. The regularity revealed is in good agreement with the observed relative
      potency of these compounds to cause dopaminergic neurodegeneration.

PMID- 1362876
TI  - Somatostatin concentrations in cerebrospinal fluid and brain tissue of patients
      with refractory epilepsy.
AB  - The somatostatin concentrations of cerebrospinal fluid (CSF) and brain tissue in
      16 refractory epileptic patients were measured simultaneously by a
      radioimmunoassay (RIA) method. An increased level of somatostatin was found in
      the epileptic foci of cerebral cortex, determined by the cortical EEG. There were
      significant differences among the epileptic foci (75.58 +/- 6.58 pg/mg wet wt, +/
      SEM), nonfocal tissues (37.04 +/- 6.55 pg/mg), and normal tissues of control
      patients (47.69 +/- 10.12 pg/mg), p < 0.001 and p < 0.05, respectively. The
      somatostatin concentrations of CSF in 11 epileptic patients were determined
      before (257.78 +/- 19.11 pg/mL) and after (178.36 +/- 8.78 pg/mL) the removal of
      epileptic focal area, and a dramatic decrease of the CSF somatostatin
      concentration after operation was detected (p < 0.01). We also found that the
      somatostatin level of cerebral scar induced by head injury in cases of
      posttraumatic epilepsy was highest (106.39 +/- 12.41 pg/mg). The results
      suggested that the surgical removal of the epileptic focal area in refractory
      epileptic patients may reduce the increased central somatostatin level, which
      could play an important part in the pathophysiological process of refractory
      epilepsy.

PMID- 1362877
TI  - [XXIII National Congress of Pediatrics. Mexico City, D.F., Mexico. 28 April-2 May
      1992. Abstracts].

PMID- 1362878
TI  - PASSHIV-1 treatment of patients with HIV-1 infection. A preliminary report of a
      phase I trial of hyperimmune porcine immunoglobulin to HIV-1.
AB  - OBJECTIVE: To study the safety of intravenously administered porcine-derived
      hyperimmune immunoglobulin to HIV-1, PASSHIV-1, in humans. METHODS: Fourteen HIV
      1-infected individuals were treated for 5-7 days with intravenous infusions of
      highly purified PASSHIV-1 (> 95% pure). Two of the 14 patients were retreated 3
      months later with PASSHIV-1 for an additional 5 days to evaluate side-effects
      from retreatment with porcine immunoglobulins. RESULTS: Ten of the patients had
      no side-effects from PASSHIV-1 therapy. Three patients experienced transient
      urticarial eruptions, which responded to antihistamine administration and did not
      require discontinuation of therapy. One patient, who received concomitant
      administration of human gammaglobulin, experienced serum sickness (type 3
      hypersensitivity reaction). All patients demonstrated a significant improvement
      in fatigue (100% response), weight (all those with previous weight loss gained
      weight), fever (100% response), polyneuropathy (100% response), bronchitis (100%
      response), candidiasis (100% response), diarrhea (100% response), and dermatitis
      (100% response). One out of the five patients with Kaposi's sarcoma demonstrated
      > 50% improvement. Mean CD4+ cell counts in the group rose from 143 +/- 263 to
      234 +/- 323 x 10(6)/l 4-6 months following completion of therapy (P = 0.013,
      paired Student's t-test); CD4+ counts rose > twofold in six individuals. p24
      antigen, present in four patients, was negative following therapy in all
      patients. Other laboratory parameters that responded to therapy included:
      platelet counts (71% response), leukopenia (57% response), elevated lactic
      dehydrogenase (100% response), and elevated alkaline phosphatase (100% response).
      PASSHIV-1 was well tolerated by HIV-1-infected individuals. CONCLUSION: This
      therapy appears to be efficacious in ameliorating some of the clinical aspects
      and symptoms of HIV-1 infection.

PMID- 1362879
TI  - Salmonella, Campylobacter and Shigella in HIV-seropositive patients.
AB  - OBJECTIVE: To study the incidence, clinical features, treatment and outcome of
      patients with Salmonella, Shigella or Campylobacter infection. DESIGN:
      Retrospective analysis. SETTING: Two dedicated HIV units within a London teaching
      hospital. METHODS: All patients with Salmonella, Shigella or Campylobacter
      infection were reviewed retrospectively by correlating the records of the
      gastrointestinal and microbiology departments with the computerized records of
      all HIV-positive patients attending the two clinics. RESULTS: Between July 1985
      and June 1991, 56 episodes of Salmonella, 37 of Campylobacter and eight of
      Shigella infection were documented in HIV-seropositive patients. Shigella was
      most likely to occur early in HIV disease, whilst patients with Campylobacter or
      Salmonella were more likely to have had a previous AIDS diagnosis. Septicaemica
      was most common in patients with Salmonella and was especially likely to occur in
      individuals with an AIDS diagnosis. Relapse of infection was common in patients
      with Salmonella, especially in those with low CD4 lymphocyte counts, those with
      an initial septicaemic illness and those not treated with ciprofloxacin.
      CONCLUSIONS: Patients with Salmonella who have low CD4 lymphocytes counts and/or
      a septicaemic illness should be considered for life-long secondary prophylaxis
      with ciprofloxacin because of the high rate of relapse observed. Administration
      of zidovudine or cotrimoxazole as prophylaxis against Pneumocystis carinii
      pneumonia may prevent the development of salmonellosis: significantly fewer
      patients with this infection were taking these drugs than patients with
      Campylobacter.

PMID- 1362880
TI  - Visceral leishmaniasis in HIV-1-infected individuals: a common opportunistic
      infection in Spain?
AB  - OBJECTIVE: To investigate the epidemiological, clinical and biological features
      of visceral leishmaniasis (VL) in patients with HIV-1 infection. DESIGN:
      Retrospective study. SETTING: Three university hospitals in southern Spain.
      PATIENTS: Forty-seven adult patients with VL and HIV-1 infection diagnosed
      between January 1986 and November 1991. RESULTS: Forty-five out of the 47 (96%)
      cases were diagnosed in the last 2 years. Fever (87%), hepatomegaly (74%),
      splenomegaly (72%) and pancytopenia (77%) were the most common presenting
      features. Most patients (79%) were strongly immunocompromised when VL was
      diagnosed, and were in stage IV of the Centers for Disease Control
      classification; 87% had a CD4 lymphocyte count < 200 x 10(6)/l. However, VL was
      the first severe infection diagnosed in 10 cases. Significant titres (> 1:40) of
      antileishmanial antibodies were detected by indirect immunofluorescence in five
      out of 16 (31%) cases only. Clinical response to the therapy was difficult to
      assess. Microbiological response was achieved in only 38% of the patients
      evaluated. CONCLUSIONS: Leishmaniasis is a relatively common infection in HIV-1
      infected individuals in southern Spain. Its clinical picture is quite uniform and
      it can be the first opportunistic infection in individuals with HIV-1. In endemic
      areas, a high index of clinical suspicion should be maintained in order to avoid
      underdiagnosis of leishmaniasis.

PMID- 1362881
TI  - A defect in tissue factor expression in monocytes from patients infected by HIV
      correlates with markers of disease progression.

PMID- 1362882
TI  - Bone-marrow diagnosis of opportunistic infections in HIV disease.

PMID- 1362883
TI  - 2-Chlorodeoxyadenosine.

PMID- 1362885
TI  - Fimbriae of Branhamella catarrhalis as possible mediators of adherence to
      pharyngeal epithelial cells.
AB  - This study attempted to elucidate the role of fimbriae in the adherence of B.
      catarrhalis to human oropharyngeal epithelial cells. Antifimbrial immune serum
      was prepared by immunization of rabbit with whole fimbriated bacteria, and
      adsorption of the serum with a nonfimbriated B. catarrhalis strain. After
      pretreatment with the antifimbrial antiserum, the adherence of fimbriated B.
      catarrhalis to human epithelial cells was significantly decreased (p < 0.05). The
      adherence was also significantly (p < 0.001) decreased by trypsin treatment.
      Electron microscopy revealed destruction of fimbriae after trypsin treatment.
      These observations suggest that fimbriae are involved in the adherence of B.
      catarrhalis to epithelial cells.

PMID- 1362884
TI  - Quantitative determination of zetidoline, a new antipsychotic agent, in human
      blood plasma and saliva using capillary gas chromatograph-mass spectrometry.
AB  - A specific and sensitive assay is described. Zetidoline is extracted with ethyl
      ether from 1 ml of plasma or saliva added with the internal standard. The extract
      is carefully purified and injected into a gas chromatography-mass spectrometry
      system equipped with a crosslinked capillary column and operated in single ion
      monitoring mode by electron impact. Quantitative response is linear in the range
      2-50 ng/ml. The detection limit is 1 ng/ml.

PMID- 1362886
TI  - CD4 lymphocyte decline and survival in human immunodeficiency virus infection.
      The Military Medical Consortium for Applied Retroviral Research.
AB  - The loss of the CD4 lymphocyte is the central pathophysiologic event in the
      progression of human immunodeficiency virus (HIV) infection. This retrospective
      study, based on review of data from deceased HIV patients followed in a single
      HIV clinic, was conducted to determine if the rate of CD4 lymphocyte decline was
      predictive of survival. Forty of 172 patients met defined criteria for inclusion
      in this study. For each patient, CD4-cell counts showed approximate exponential
      decline over time. A Cox regression analysis was used to assess the association
      of CD4 cell decline (half-life), race, age, gender, initial CD4-cell count, and
      treatment (anti-Pneumocystis carinii pneumonia prophylaxis and/or zidovudine vs.
      no therapy) on total survival (from initial CD4 cell count) and on remaining
      survival time after reaching a CD4 cell count of 100 (estimated). For all
      patients, the rate of CD4 cell decline was predictive of total survival (p =
      .009) but not for survival after reaching a count of 100 (p = .6). For patients
      who had never received therapy (6 patients), however, the CD4 half-life remained
      associated with survival time from 100 CD4 cells (p < .05) as opposed to the
      treated patients. Therapy was the single variable most predictive of both
      survival endpoints, resulting in an increase in median total survival of 27.2 mo
      (p < .00001) and of 15.4 mo from a CD4 cell count of 100 (p < .00004). Nonwhites
      had a slight survival disadvantage compared to whites (p = .08 overall; p = .02
      from CD4 cell count of 100).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362887
TI  - A preliminary, clinical pharmacological assessment of L-659,066, a novel alpha 2
      adrenoceptor antagonist.
AB  - 1. The alpha 2-adrenoceptor antagonist activity of L-659,066 has been
      investigated in studies of healthy normotensive males to whom doses of up to 8 mg
      were administered by short intravenous infusion. 2. L-659,066 had no effect on
      basal levels of glucose or insulin and no significant effect on the plasma
      glucose and plasma insulin time profiles following an intravenous glucose load.
      3. There was a non-significant trend for plasma noradrenaline concentrations to
      be higher after L-659,066. 4. L-659,066 had no significant effects on mood
      changes or on physical symptom scores. 5. There were no significant effects on
      supine blood pressure but there were consistent increases in heart rate both
      supine (non-significant) and erect (P < 0.01). 6. Ex vivo platelet aggregation
      studies confirmed alpha 2-adrenoceptor antagonist activity with L-659,066 but
      with an approximately 9-fold lesser potency than yohimbine. 7. While L-659,066
      has alpha 2-adrenoceptor antagonist activity these results suggest that it is
      unlikely to present a new therapeutic approach for improving insulin release.

PMID- 1362888
TI  - Effect of 3 weeks treatment with yohimbine on salivary secretion in healthy
      volunteers and in depressed patients treated with tricyclic antidepressants.
AB  - The effect of yohimbine treatment (4 mg three times daily) for 3 weeks on
      salivary secretion was investigated. In healthy volunteers, acute administration
      of yohimbine increased salivary volume within 1 h to a similar extent before and
      at the end of the treatment period. In depressed patients treated with tricyclic
      antidepressants (and exhibiting a reduced salivary flow), yohimbine also acutely
      increased salivary volume. In contrast, the alpha 2-adrenoceptor antagonist
      failed to modify resting values measured in the morning (i.e. 10 and 14 h after
      the last administration in healthy volunteers and depressed patients
      respectively). This result indicates that alpha 2-adrenoceptor antagonists may
      have a potential therapeutic use in the treatment of dry mouth caused by
      tricyclic antidepressant drugs.

PMID- 1362889
TI  - Diagnosis of drug-induced psoriasis.
AB  - Certain drugs have been reported to precipitate or to exacerbate psoriasis. These
      cases occur mostly in patients with a history of psoriasis, although occasionally
      the new onset of psoriasis has followed treatment with certain drugs. The suspect
      drugs include lithium, beta adrenergic antagonists, antimalarials, and non
      steroidal anti-inflammatory drugs (NSAID), in addition to various miscellaneous
      agents, including tetracycline. Evidence for these reports must be critically
      examined based on clinical and histological data, time course between drug intake
      and psoriasis exacerbation or resistance to psoriasis therapy, and response to
      drug rechallenge when available. The clinical context must be taken into
      consideration, including effects of concomitant antipsoriatic therapy, and the
      possible role of other triggering factors, such as infection. Controlled,
      prospective studies of the use of NSAID in patients with psoriasis may help to
      clarify their varied cutaneous effects. Further knowledge of the mechanisms
      involved in drug exacerbation of psoriasis may help to elucidate the
      etiopathogenesis of this chronic skin disorder.

PMID- 1362890
TI  - Psoriasis Symposium. Proceedings. Kauai, Hawaii, February 20, 1992.

PMID- 1362892
TI  - Clinical Biochemistry in Renal Diseases: Basic Knowledge and Diagnostic
      Approaches. Proceedings of international symposium. Gdansk, September 4-6, 1991.

PMID- 1362891
TI  - Replacement of butter on bread by rapeseed oil and rapeseed oil-containing
      margarine: effects on plasma fatty acid composition and serum cholesterol.
AB  - The effects of zero-erucic acid rapeseed oil and rapeseed oil-containing
      margarine on plasma fatty acid composition and serum cholesterol were studied in
      butter users (n 43). Compliance to the substitution was followed by fatty acid
      analysis of total plasma and plasma phospholipids. The amount of substitute fats
      represented, on average, 21% of total fat and 8% of total energy intake. Changes
      in the relative fatty acid composition of plasma phospholipids indicated further
      fatty acid metabolism, and were closely related to the serum cholesterol level.
      The reduction in saturated fatty acids led to a significant increase in the
      proportion of n-3 and n-6 polyunsaturated fatty acids (PUFA) with the rapeseed
      oil diet, whereas the margarine caused a significant rise in n-6 PUFA only. The
      increase in the proportions of the two PUFA families occurred in accordance with
      their competitive order, most completely with the rapeseed oil diet. When butter
      was replaced by rapeseed oil, low-density-lipoprotein-cholesterol decreased by an
      average of 9.1% without a reduction in high-density-lipoprotein-cholesterol.
      During margarine substitution the reduction was 5.2%, on average. Of the plasma
      phospholipids, alpha-linolenic acid and the linoleic:stearic acid ratio, but not
      oleic acid, were the components most significantly correlated with serum
      cholesterol levels or the decrease in these levels. The results show that
      rapeseed oil can act primarily as a source of essential fatty acids, rather than
      that of monoenes, in the diet of butter users.

PMID- 1362893
TI  - Clinical biochemistry in renal diseases basic knowledge and diagnostic
      approaches. Report on the international symposium, held in Gdansk, Poland,
      September 4th to 6th, 1991.

PMID- 1362894
TI  - Biochemical and immunological properties of urinary angiotensinase A and
      dipeptidylaminopeptidase IV. Their use as markers in patients with renal cell
      injury.
AB  - Dipeptidyl peptidase IV (EC 3.4.14.5) and angiotensinase A (EC 4.4.11.7) were
      purified to homogeneity from pooled urine concentrate of patients with renal
      damage, using ultrafiltration, ammonium sulphate precipitation, lectin affinity
      chromatography, FPLC-ion-exchange(Mono-Q-)chromatography, and FPLC-gel filtration
      (Superdex). Based on the specific enzyme activity of the starting material,
      dipeptidyl peptidase IV was enriched 1629 fold, angiotensinase A 1183 fold. The
      relative molecular masses, Michaelis constants and isoelectric points were
      determined. Negative staining of the purified enzymes revealed globular proteins
      (5-7 nm). Antisera raised against dipeptidyl peptidase IV and angiotensinase A
      reacted specifically with tubular and, in the case of anti-angiotensinase A sera,
      with tubular and glomerular structures. In addition, urinary membrane vesicles of
      proximal tubule origin were eluted with the void volume (Superdex-gel
      filtration), indicating heavy epithelial cell disintegration. Both soluble tissue
      enzymes (dipeptidyl peptidase IV, angiotensinase A) and vacuolar blebs shed from
      epithelia contribute to proteinuria, as was shown in patients with
      glomerulonephritis, interstitial nephritis, diabetic nephropathy and, for
      angiotensinase A, in patients with essential arterial hypertension.

PMID- 1362895
TI  - Effects of intracerebroventricular administration of D,L-2-amino-5
      phosphonovaleric acid, an N-methyl-D-aspartate receptor antagonist, on
      luteininizing hormone release in ovariectomized lambs.
AB  - To determine whether endogenous glutamate and aspartate control LH secretion via
      N-methyl-D-aspartate (NMDA) receptors in the sheep, we evaluated the effects of
      the NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (AP5) on
      secretion of LH in ovariectomized lambs. Twelve lambs were ovariectomized and
      surgically implanted with lateral cerebroventricular cannulae. At the time of the
      experiment, (38 wk of age) they received intracerebrally 4 injections of either
      50 (n = 4), 100 (n = 4), or 200 micrograms (n = 4) of AP5. Blood samples were
      collected every 10 min for 8 h with animals receiving AP5 at hours 4, 5, 6, and
      7. Patterns of LH during the preinjection period were compared to those during
      the period encompassing AP5 injections. Mean concentrations of LH were lower
      during AP5 injections than during the preinjection periods, a response that was
      not influenced by dose (0.87 +/- 0.08 vs. 0.69 +/- .07 ng/ml; p < 0.01). LH pulse
      amplitude decreased during AP5 treatment relative to the preinjection periods,
      but this difference was not statistically significant (0.79 +/- 0.11 vs. 0.68 +/-
      0.10 ng/ml; p = 0.09). There were no effects of AP5 on LH pulse frequency (1.00
      +/- 0.10 vs. 0.83 +/- 0.15 pulses/h for injection and preinjection periods; p >
      0.10). A second experiment was done to evaluate a higher dose of AP5. Four
      animals were chosen to receive 4 injections of 2 mg of AP5 in a design identical
      to that used in the first experiment.

PMID- 1362896
TI  - Biochemical characterization of phosphoinositide hydrolysis stimulated by 5-HT3
      receptor agonists.
AB  - Serotonin (5-HT) stimulates phosphoinositide (PI) turnover in rat fronto
      cingulate cortical slices and is probably mediated through the activation of both
      5-HT2 and 5-HT3 receptors. We have extended these findings and have assessed
      whether the increased stimulation of PI turnover is secondary to 5-HT stimulated
      arachidonate metabolism or to the release of another neurotransmitter. Incubation
      of the cortical slices by the two 5-HT3 receptor agonists, 2-methyl-serotonin (2
      Me-5-HT) and phenylbiguanide (PBG), significantly decreases serotonin-stimulated
      phosphoinositide turnover, indicating that activation of 5-HT3, receptors by 2-Me
      5-HT and PBG caused the desensitized PI hydrolysis to 5-HT. Indomethacin did not
      affect the increased PI hydrolysis induced by 5-HT, 2-Me-5-HT and PBG, suggesting
      that neither cyclooxygenase nor lipoxgenase activity is required for the PI
      response and that it is independent of arachidonic acid metabolism. The
      stimulation in PI turnover induced by 5-HT and the 5-HT3 receptor agonists was
      not potentiated by proteinase inhibitors suggesting that the release of a peptide
      neurotransmitter is not involved in the PI response. In addition, the effects of
      5-HT, 2-Me-5-HT and PBG on PI turnover are additive to the effect of KCl and
      veratrine. In conclusion, our results indicate that the action of 2-Me-5-HT and
      PBG on PI turnover is direct.

PMID- 1362897
TI  - Muscarinic inhibition of reticular thalamic cells by basal forebrain neurones.
AB  - Pressure injections of a Ringer's solution containing glutamate (10 or 20 mM)
      into the nucleus basalis of Meynert inhibited the tonic firing of reticular
      thalamic (RT) neurones which were recorded in rats under deep urethane
      anaesthesia. When the inhibition was strong enough to stop the discharges, a
      burst firing mode was induced in RT cells before the recovery of tonic
      discharges. This glutamate-induced inhibition of RT cells was completely
      abolished following the systemic administration of the muscarinic antagonist,
      scopolamine (150 micrograms kg-1, i.v.). These results indicate that the
      cholinergic cells of the nucleus basalis of Meynert can control the mode of
      discharges of RT neurones through the activation of muscarinic receptors.

PMID- 1362899
TI  - No association or linkage with HLA-DR or -DQ genes in south Indians with
      pulmonary tuberculosis.
AB  - Studies of the HLA class II genes were performed in patients and multiple
      families with pulmonary tuberculosis from South India to seek any association of
      disease susceptibility with an individual allele or haplotype. TaqI RFLP analysis
      of HLA-DRB, -DQA and -DQB genes was done in 38 patients and 36 healthy control
      subjects. No significant association with any particular allele or haplotype was
      obtained. Linkage analysis performed in 12 families and haplotype sharing
      analysis in 9 families showed that the genetic susceptibility to pulmonary
      tuberculosis was not linked to the HLA region. The results suggest that the RFLP
      patterns of HLA class II genes DRB, DQA and DQB are not associated with
      susceptibility to pulmonary tuberculosis and that the genes controlling
      susceptibility or resistance may be located outside the HLA region.

PMID- 1362898
TI  - Chronic nicotine treatment decreases dopamine D2 agonist binding in the rat basal
      ganglia.
AB  - To elucidate possible actions of nicotine on dopamine D2 receptor binding, the
      effect of chronic continuous (-)nicotine treatment (osmotic pumps s.c., 0.125 mg
      kg h-2, 14 days) was studied in the binding of [3H]N-propylnorapomorphine
      ([3H]NPA) and [125I]sulpride in coronal cryostat sections in the rat.
      Quantitative autoradiography showed that nicotine decreased the binding of
      [3H]NPA in the basal ganglia, preferentially in the nucleus accumbens and
      olfactory tubercle. In contrast, [125I]sulpride binding was not affected.
      Nicotine decreased the KD value of [3H]NPA by 27% and decreased the Bmax value by
      17%, using filter-wiped sections. These results indicate that chronic continuous
      nicotine treatment affects the D2 receptor and that this effect may be involved
      in the development of nicotine dependence.

PMID- 1362900
TI  - [Multivisceral and extended resection in pancreatic cancer].
AB  - Out of 303 pancreatoduodenectomies performed for carcinoma in the past 19 years,
      100 patients required a multivisceral or (in 39 cases) a regional pancreatectomy.
      Although the operative and hospital mortality for these extended resections was
      only 2%, long-term survival (only 1 patient survived more than 5 years) was
      inferior to conventional radical pancreatoduodenectomy with a 25% 5-year survival
      rate.

PMID- 1362902
TI  - 1st Conference of the International Federation of Toxicologic Pathologists
      (IFSTP). Proceedings. Nagoya, Japan, April 22-24, 1992.

PMID- 1362901
TI  - The role of Gln61 and Glu63 of Ras GTPases in their activation by NF1 and Ras
      GAP.
AB  - Two distinct GAPs of 120 and 235 kDa called GAP1 and NF1 serve as attenuators of
      Ras, a member of GTP-dependent signal transducers, by stimulating its intrinsic
      guanosine triphosphatase (GTPase) activity. The GAP1 (also called Ras GAP) is
      highly specific for Ras and does not stimulate the intrinsic GTPase activity of
      Rap1 or Rho. Using GAP1C, the C-terminal GTPase activating domain (residues 720
      1044) of bovine GAP1, we have shown previously that the GAP1 specificity is
      determined by the Ras domain (residues 61-65) where Gln61 plays the primary role.
      The corresponding domain (residues 1175-1531) of human NF1 (called NF1C), which
      shares only 26% sequence identity with the GAP1C, also activates Ras GTPases. In
      this article, we demonstrate that the NF1C, like the GAP1C, is highly specific
      for Ras and does not activate either Rap1 or Rho GTPases. Furthermore, using a
      series of chimeric Ras/Rap1 and mutated Ras GTPases, we show that Gln at position
      61 of the GTPases primarily determines that NF1C as well as GAP1C activates Ras
      GTPases, but not Rap1 GTPases, and Glu at position 63 of the GTPases is required
      for maximizing the sensitivity of Ras GTPases to both NF1C and GAP1C.
      Interestingly, replacement of Glu63 of c-HaRas by Lys reduces its intrinsic
      GTPase activity and abolishes the GTPase activation by both NF1C and GAP1C. Thus,
      the potentiation of oncogenicity by Lys63 mutation of c-HaRas appears primarily
      to be due to the loss of its sensitivity to the two major Ras signal attenuators
      (NF1 and GAP1).

PMID- 1362903
TI  - Antithyroid drug effects on function and growth of FRTL-5 cells.
AB  - Although antithyroid drugs (ATDs) are known to exert their effects by inhibiting
      iodide organification within the thyroid follicular cell, a full understanding of
      their mechanisms of action is lacking. In this study the effects of methimazole
      (MMI) and propylthiouracil (PTU) on thyrotropin (TSH) and thyroid-stimulating
      immunoglobin (TSI)-stimulated cAMP production and growth in FRTL-5 cells was
      investigated. MMI, but not PTU, inhibited TSH-stimulated cAMP production, but
      only at the very highest concentration (10(-3) M): 0.3 +/- 0.01 vs 0.79 +/- 0.13
      pmol/micrograms protein (p < 0.01). Neither MMI nor PTU inhibited TSI-stimulated
      cAMP production at any dose. Neither MMI nor PTU exhibited an inhibitory effect
      on TSH- or TSI-stimulated cell growth, as measured by [3H]-thymidine
      incorporation. These observations suggest that high concentrations of MMI may act
      to control thyroid function by inhibiting receptor-mediated cAMP production.
      Although decreases in thyroid gland size frequently occur during ATD therapy,
      neither MMI nor PTU exhibited any effect on TSH- or TSI-stimulated thyroid cell
      growth.

PMID- 1362904
TI  - [Genetic counseling].

PMID- 1362905
TI  - [Hepatocellular carcinoma: 30 years' experience in Taiwan].

PMID- 1362906
TI  - [Natural history of hepatitis B and D virus infections].

PMID- 1362907
TI  - [The management of obstructive jaundice caused by pancreatic head carcinoma and
      periampullary carcinoma].
AB  - We had treated 115 patients with malignant obstructive jaundice, including 69
      pancreatic head carcinoma and 46 periampullary carcinoma during the period
      between 1982 and 1991. In the 115 jaundiced patients 33 had undergone
      pancreaticoduodenectomy, 50 had bypass operation and the remaining 32 patients
      undergone percutaneous transhepatic biliary drainage (PTBD) only. No operative
      mortality happened for the 33 pancreaticoduodenectomies. Postoperative
      complications occurred in 12 patients. Leakage from the choledochojejunostomy was
      the most often occurred complications, it was found in 7 patients (21.2%).
      Intraabdominal abscesses happened in six patients (18.2%) which recovered by
      treating with ultrasound-guided catheteral drainage. Leakage from
      pancreaticojejunostomy was also found in five patients (15.2%), the complication
      recovered uneventfully after administration of total parenteral nutrition and
      good abdominal drainage. Twenty-two out 33 patients with pancreaticoduodenectomy
      received preoperative biliary drainage. However, despite preoperative biliary
      drainage, 10 of 22 patients (45.5%) still suffered postoperative complications.
      It implied that hyperbilirubinemia would trend to carry a high postoperative
      morbility. The prognosis for our patients with pancreatic head carcinoma was
      extremely poor. The mean survival period for all of them was not exceeding 12
      months. Those who had PTBD as the sole treatment had the shortest survival
      period, which was 3.4 +/- 3.1 months only. On the other hand, the mean survival
      period for those who had periampullary cancer and had pancreaticoduodenectomy was
      35.5 +/- 27.2 months, while it was 13.3 +/- 10.1 and 11.8 +/- 10.0 months for
      those having bypass operation and PTBD respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1362908
TI  - [Indications and contraindications of digital replantation].
AB  - With the development of microsurgery, replantation surgery have become the method
      of choice in treating the digit amputations. Although better than 90% of
      successful rate can be achieved in replanting guillotine type amputation, the
      final functional recovery is the main goal. The indications include: (1) thumb
      amputations, (2) Zone I amputation, (3) multiple digits, (4) bilateral
      amputation, (5) hemi-hand amputations, (6) hand amputation at wrist to upper
      forearm, and (7) pediatric amputations. And the contraindications include: (1)
      life-threatening associated injuries, (2) technically impossible, and (3) self
      inflicted injuries. As for condition which have been previously put in the
      contraindication categories, such as: (1) single finger amputation, (2) Zone II
      amputations, (3) severe crush or avulsion injuries, (4) geriatric amputations,
      and (5) lengthy ischemia time amputations, the decision of to replant or not to
      replant was not a straight forward one. The decisions are individualized to meet
      the needs of different patients.

PMID- 1362909
TI  - [Risk factors of lung cancer].
AB  - The relationship between various risk factors and lung cancer was evaluated in a
      case-control study. One hundred and forty-one cancer patients newly cytologically
      or pathologically diagnosed from May 1990 to July 1991 at Tri-Service General
      Hospital (TSGH) were recruited as cases. Two control groups were also studied:
      282 hospital controls two-to-one matched with cases on sex, age, hospital of
      admission and insurance status were selected from the TSGH Ophthalmologic
      Department, and 282 neighborhood controls two-to-one matched on sex, age, and
      residence were randomly selected from eligible neighbors. A comparison of
      interview data between cases and hospital controls based on multiple conditional
      logistic regression revealed that cigarette smoking, keeping doves as pet,
      occupational exposure to cotton dust and working as a cook were risk factors for
      lung cancer. An inverse association between incense burning and lung cancer was
      noted. The comparison between cases and neighborhood controls showed lung cancer
      was significantly associated with cigarette smoking, keeping doves, prior chronic
      bronchitis, occupational exposure to cotton dust, asbestos and radiation, low
      frequency of burning incense, and low intake of vitamin A derived from vegetables
      and fruits. There was no association between lung cancer and working as a cook
      when cases were compared with neighborhood controls.

PMID- 1362910
TI  - [Sleep quality and nocturnal hypoxemia in patients with chronic obstructive
      pulmonary disease].
AB  - To evaluate the incidence of sleep apnea syndrome (SAS), oxygen desaturation
      during sleep and sleep quality in patients with chronic obstructive pulmonary
      disease (COPD), 30 COPD patients and 20 healthy snorers (without SAS) were
      studied. Each subject received a pulmonary function test (PFT) (simple
      spirometry), arterial blood gas determination and an overnight sleep study. COPD
      patients were divided into two groups: those with SAS (group I) and those without
      (group II). Group II patients were further subdivided into: group IIa [delta SaO2
      < 15% (delta SaO2 = baseline SaO2-lowest SaO2) and group IIb (delta SaO2 > or =
      15%); group IIc (baseline SaO2 > 90%) and group IId (baseline SaO2 < or = 90%).
      Our results showed that only six of 30 (20%) COPD patients had an associated SAS.
      Among group II patients, the lowest SaO2 and delta SaO2 were correlated with
      baseline SaO2, PaO2 and PaCO2 but were not correlated with age, % of ideal body
      weight, FVC, FEVl, FEVl/FVC. Group IIb patients (n = 10) had a lower SaO2 during
      sleep, a lower baseline PaO2, and a lower hematocrit level than group IIa
      patients (n = 14). Group IId patients (n = 9) had a lower PaO2 and a higher delta
      SaO2 during sleep than group IIc patients (n = 15). However, there were no
      significant differences in age, percent of ideal body weight (IBW), FVC, FEVl or
      FEVl/FVC values between groups IIa and IIb, or between groups IIc and IId. Group
      II patients had a lower percentage of sleep efficiency, higher arousal and
      movement indices and a longer period of stage 1 sleep, compared to the control
      group. In conclusion, the incidence of COPD patients with SAS is 20%. Age,
      percentage of IBW, FEVl, and FEVl/FVC values are not reliable predictors of the
      risk of nocturnal hypoxemia among COPD patients. However, a possible correlation
      between baseline SaO2, PaO2 and PaCO2 values and the incidence of nocturnal
      hypoxemia exists. Finally, COPD patients experienced a poorer quality of sleep in
      comparison with the control group.

PMID- 1362911
TI  - [Preliminary study of cartilage repair with autologous periosteum and fibrin
      adhesive system].
AB  - The potential surgical transplantation with autogenous periosteal grafts and
      Fibrin Adhesive System (FAS) was attempted in a rabbit model. The grafts were
      taken from the tibia, transplanted and fixed with FAS to artificial full
      thickness (0.4 x 0.3 cm) defect on the femoral condyle. Histologic and
      ultrastructural findings revealed chondrocyte regeneration in the control,
      grafted, and graft/FAS treated group at week 6; however, chondrogenesis of the
      reparative tissue was best demonstrated in the graft/FAS group. At week 12, the
      interface between the reparative tissue and the surrounding tissue was invisible
      in the FAS/graft group, as compared with the well-defined interface in the
      grafted group and the control. The results strongly suggest that FAS-treated
      periosteal transplant is a potential model for the repair of articular cartilage
      defects. Although the results are preliminary, all seem promising in the clinical
      aspects.

PMID- 1362912
TI  - [Effect of fibrin on nerve regeneration in a silicone chamber].
AB  - When regenerating from an injury, fluid containing nerve growth-promoting
      components such as the nerve growth factor (NGF) will accumulate around the stump
      of a cut nerve within 24 hours. It has been found that this fluid also contains
      fibrin. To evaluate the effect of fibrin on nerve regeneration, we cut both
      facial nerves of 40 guinea pigs and sutured both ends of the nerve stumps to
      silicone tubes. The distance between the stumps were kept at around 8 mm in the
      silicone chamber. Autogenous fibrin isolated from the blood of each guinea pig
      was injected into the silicone chamber on the left side, while lactate Ringer's
      solution was injected into the silicone chamber on the right side as a control.
      The status of nerve regeneration in both sides of the silicone chambers were
      later evaluated at 3 and 5 weeks. Histological study revealed that after
      regeneration for 3 weeks, the total axon number and the fascicular number
      increased significantly in the fibrin-filled chamber. However, after 5 weeks,
      there was no significant difference in nerve regeneration between the two groups.

PMID- 1362913
TI  - [Influence of haloperidol on plasma Li+ and Li+ index].
AB  - Since Cohen and Cohen reported four cases suffering from irreversible brain
      damage after combined use of haloperidol and lithium, the possible toxic
      interaction between these two drugs has been intensively studied. The results are
      controversial. In this study, we used the within-Ss design to study the influence
      of haloperidol on the plasma Li+ level and Li+ index in 29 manic patients. Also,
      we used the in vitro method to study the influence of haloperidol on the Li+
      index in 36 healthy volunteers. Haloperidol significantly increased the plasma
      Li+ levels (paired t test, t = 2.797, d.f. = 27, p < 0.01) in the in vivo study,
      but did not alter the Li+ index in either the in vivo or the in vitro study.

PMID- 1362914
TI  - [Parathyroid storm: report of two cases].
AB  - Parathyroid storm in patients with primary hyperparathyroidism has previously
      been described as hyperparathyroid crisis, parathyroid intoxication or acute
      hyperparathyroidism. Whatever the nomenclature, all emphasize the severity and
      urgency of this disease entity. Although fewer than 200 cases have been described
      since the first report by Dawson in 1932, it is generally agreed that parathyroid
      storm is more prevalent than commonly appreciated. The symptoms and signs of the
      syndrome are not only due to the hypercalcemia, but also to the toxic effects of
      the parathyroid hormone (PTH). Its wide, but nonspecific clinical presentations
      make it easily confused with other cardiovascular or renal diseases. The
      mortality rate in untreated cases of parathyroid storm is essentially 100%. With
      combined medical-surgical treatment, it is still reported to be as high as 40%.
      Two patients with parathyroid storm were encountered at our institute recently,
      they both presented with severe hypercalcemia, consciousness disturbance and
      acute renal failure. The serum level of the intact form of PTH (iPTH) in both
      patients was greater than 1,000 pg/mL. Case 1, a 63-year-old female, presented
      with hypercalcemic crisis. Initially, good responsiveness to a saline infusion,
      steroids and furosemide administration was noted. Unfortunately, she became
      comatous after fine-needle aspiration of the parathyroid tumor. The recurrent
      storm was refractory to medical therapy, but was treated successfully by surgical
      removal of the single adenoma. This is a rare reported case regarding a
      hyperparathyroid storm after fine-needle aspiration of a parathyroid
      adenoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362915
TI  - Paradoxical bronchoconstriction and salmeterol.

PMID- 1362916
TI  - Resistance of chronic lymphocytic leukaemia cells to interferon-alpha generated
      lymphokine activated killer cells.
AB  - Recent studies have shown that, when used in early stage disease, interferon
      alpha (IFN-alpha) can produce a fall in the number of malignant cells in the
      peripheral blood of patients with B-CLL. In this study, we investigated the
      effect of IFN-alpha on natural killer (NK) cell and lymphokine-activated cell
      (LAK) activity in patients with B-CLL. In vitro, IFN-alpha (500 U/ml for 18
      hours) induced LAK activity in patients with B-CLL (27.7 +/- 9.9%, n = 20), and
      IL-2 (500 U/ml for 5 days) produced similar activity (35.9 +/- 8.8%, n = 7).
      Despite the induction of LAK activity by IFN-alpha and IL2 in patients with B
      CLL, the malignant cells remained resistant to both allogeneic and autologous LAK
      effectors. NK activity in patients with B-CLL is also low (23.1 +/- 7.2%, n =
      20), and B-CLL cells were resistant to NK cell activity. In cold target
      competition assays, CLL cells did not compete with labelled K562 or Daudi targets
      in the NK and LAK assays, suggesting that the malignant cells are not recognised
      by the effector cells, and this may be related to low level of expression of the
      adhesion receptors, LFA-1 and ICAM-1. Finally, CLL cells were also resistant to
      antibody dependent cell mediated cytotoxicity, but were susceptible to antibody
      dependent complement mediated lysis. These results suggest that it is unlikely
      that the effects of IFN-alpha in B-CLL are due to the enhancement of NK or LAK
      activity.

PMID- 1362918
TI  - Autologous blood stem cell transplantation in malignant lymphomas: an Italian
      Cooperative Study.
AB  - Twenty-three patients with malignant lymphoma, (7 Hodgkin's, and 16 non
      Hodgkin's) in different phases of disease were autografted in 4 Italian
      Haematology institutions using only chemotherapy-mobilized blood stem cells (BSC)
      collected by apheresis. Clinical and laboratory data were analysed centrally and
      showed mean collection yields of 8.1 x 10(8) kg mononuclear cells (MNC) (SE 0.5;
      range 2.6-13.8) and 24.1 x 10(4) kg CFU-GM (SE 7.4; range 1.4-162.9). The mean
      times required to attain 0.5 x 10(9)/l neutrophils and 50 x 10(9)/l platelets
      after marrow-ablative high-dose chemo+radiotherapy and BSC reinfusion were 14.9
      days (SE 1.5; range 7-38) and 18.6 days (SE 2.6; range 6-49) respectively. The
      incidence of early deaths was < 5% and the requirement for support with blood
      product transfusion was moderate. The progression free survival (PFS) is > 50% at
      3 years with a median follow-up of 17.3 months. Results were significantly better
      for patients autografted in remission. These results suggest that autologous
      blood stem cell transplantation (ABSCT) may be proposed for the primary treatment
      of poor prognosis malignant lymphomas. However, ABSCT needs to be compared with
      autologous bone marrow transplantation (ABMT) followed by infusion of growth
      factors to accelerate recovery.

PMID- 1362917
TI  - Demonstration of HTLV-related proviral DNA sequences and antibodies reactive with
      HTLV internal proteins in an Hungarian patient with Sezary syndrome.
AB  - DNA sequences distantly related to the proviral DNA of HTLV-I were found in the
      leukemic cells of a Hungarian patient suffering from Sezary syndrome. Serum
      samples from the patient contained antibodies reactive with the internal core
      polypeptides of HTLV-I and HTLV-II, but not with the env gene encoded type
      specific HTLV antigens. The husband and daughter of the patient also had
      antibodies of the same specificity. These findings suggest the presence of a
      virus distantly related to HTLV-I and HTLV-II.

PMID- 1362919
TI  - Expression and functional role of CD54/Intercellular Adhesion Molecule-1 (ICAM-1)
      on human blood cells.
AB  - CD54/Intercellular Adhesion Molecule-1 (ICAM-1) is a cell adhesion molecule
      largely distributed among normal and neoplastic tissues. Through the binding to
      its ligand(s) CD54 plays a key role in cell to cell interactions leading to the
      immune response. Recently, CD54 expression has been investigated on hematopoietic
      cells: the antigen is predominantly expressed in the early stages of normal
      hematopoiesis and during the activation of blood cells. As regards to
      hematological malignancies, CD54 is strongly expressed on neoplastic cells from
      "stem cell derived" neoplasms. In AML, CD54 expression is related with other
      differentiation-linked molecules such as CD34 and HLA-DR and is significantly
      correlated with FAB morphological classification. In lymphoproliferative
      disorders, a high CD54 expression is associated with germinal centre lymphomas.
      This review summarizes our current understanding of CD54 with emphasis on recent
      advances and reference to unresolved issues such as its prognostic role in the
      clinical outcome of oncohematological diseases.

PMID- 1362920
TI  - Effect of serotonergic agents on regional concentrations of somatostatin- and
      neuropeptide Y-like immunoreactivities in rat brain.
AB  - A possible role for neuropeptides in affective disorders is suggested by many
      investigators. Somatostatin-like immunoreactivity (SS-LI) and neuropeptide Y-like
      immunoreactivity (NPY-LI) concentrations are demonstrated to be reduced in
      cerebrospinal fluid from depressed patients. We have shown that long-term
      treatment with serotonin uptake inhibitors, clomipramine and zimelidine, reduce
      brain SS-LI concentrations in the rat. We have studied the effect of serotonergic
      agents on regional brain SS-LI and NPY-LI concentrations in rats. Long-term
      treatment with 5-hydroxytryptamine (5-HTP), a serotonin precursor, caused
      reductions in SS- and NPY-LI levels in the hypothalamus. SS- and NPY-LI
      concentrations in the brain were markedly elevated by treatment with p
      chlorophenylalanine, a serotonin synthesis inhibitor. Intracerebroventricular
      administration of 5,7-dihydroxytryptamine, a serotonin neurotoxin, resulted in
      elevations of both peptides in the brain. These results suggest a inhibitory role
      for the serotonergic system in the brain in the regulation of SS and NPY.

PMID- 1362921
TI  - Protection from 1-methyl-4-phenylpyridinium (MPP+) toxicity and stimulation of
      regrowth of MPP(+)-damaged dopaminergic fibers by treatment of mesencephalic
      cultures with EGF and basic FGF.
AB  - Several peptide growth factors can maintain survival or promote recovery of
      injured central neurons. In the present study, the effects of epidermal growth
      factor (EGF) and basic fibroblast growth factor (bFGF) on the toxicity produced
      by the dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium (MPP+), were
      investigated in rat mesencephalic dopaminergic neurons in culture. High affinity
      [3H]DA uptake and morphometric analyses of tyrosine hydroxylase immunostained
      neurons were used to assess the extent of MPP+ toxicity, dopaminergic neuronal
      survival and growth of neurites. Consistent with previous reports, EGF and bFGF
      treatments stimulated neuritic outgrowth in dopaminergic neurons, increased DA
      uptake and enhanced their long-term survival in vitro. These growth factors also
      stimulated proliferation of astrocytes. The time course of EGF and bFGF effects
      on dopaminergic neurons coincided with the increase in glial cell density,
      suggesting that proliferation of glia mediates their trophic effects. Several
      findings from our study support this possibility. When MPP+ was applied to
      cultures at 4 days in vitro, before glial cells had proliferated, the damage to
      dopaminergic neurons was not affected by EGF or bFGF pretreatments. However, when
      cultures maintained in the presence of the growth factors for 10 days were
      exposed to MPP+, after they had become confluent with dividing glial cells, the
      MPP(+)-induced decreases in DA uptake and cell survival were significantly
      attenuated. Furthermore, when glial cell proliferation was inhibited by 5-fluoro
      2'-deoxyuridine, the protective effects of EGF and bFGF against MPP+ toxicity
      were abolished. Continuous treatment of MPP(+)-exposed cultures with EGF or bFGF
      resulted in the stimulation of process regrowth of damaged dopaminergic neurons
      with concomitant recovery of DA uptake, suggesting that the injured neurons are
      able to respond to the trophic effects of EGF and bFGF. In summary, our study
      shows that the trophic effects of EGF and bFGF on mesencephalic dopaminergic
      neurons include protection from the toxicity produced by MPP+ and promotion of
      recovery of MPP(+)-damaged neurons. Stimulation of glial cell proliferation is
      necessary for these effects.

PMID- 1362922
TI  - Lipogenesis in turkeys and chickens: a study of body composition and liver
      lipogenic enzyme activities.
AB  - 1. Carcase composition, fat deposition and the activities of three liver
      lipogenic enzymes were compared in turkeys and chickens fed ad libitum on two
      different isocaloric diets, respectively adapted to chickens (C) and to turkeys
      (T). Diets differed in their protein content, being higher by 60 g/kg in diet T.
      2. Chickens were much fatter than turkeys and exhibited higher activities of
      acetyl-coenzyme A carboxylase (EC 6.4.1.2) and malic enzyme (EC 1.1.1.40). 3. The
      carcase composition of turkeys was not influenced by the type of diet
      administered, while chickens fed on diet C were fatter than chickens fed on diet
      T. Compared to diet T, diet C enhanced malic enzyme activity, whatever the
      species and age. 4. A good correlation between abdominal fat and total fatness
      was observed in both species but especially in turkeys. 5. In conclusion, hepatic
      lipogenesis is much lower in turkeys than in chickens.

PMID- 1362923
TI  - Role of the sympathetic nervous system in the alcohol-guanabenz hemodynamic
      interaction.
AB  - The present study evaluated the contribution of the sympathetic nervous system to
      the adverse hemodynamic action of ethanol on hypotensive responses in conscious
      unrestrained spontaneously hypertensive rats. Ethanol caused a dose-related
      attenuation of the hypotensive effect of guanabenz. An equivalent hypotensive
      response to sodium nitroprusside was not influenced by ethanol, which indicates a
      potential specific interaction between ethanol and guanabenz. Alternatively, it
      is possible that a preexisting high sympathetic nervous system activity, which
      occurred during nitroprusside infusion, may mask a sympathoexcitatory action of
      ethanol. Further, ethanol (1 g/kg) failed to reverse the hypotensive effect of
      the ganglionic blocker hexamethonium. This suggests that a centrally mediated
      sympathoexcitatory action of ethanol is involved, at least partly, in the
      reversal of hypotension. In addition, the antagonistic interaction between
      ethanol and guanabenz seems to take place within the central nervous system and
      involves opposite effects on central sympathetic tone. Finally, changes in plasma
      catecholamines provide supportive evidence for the involvement of the sympathetic
      nervous system in this interaction. In a separate group of conscious
      spontaneously hypertensive rats, ethanol (1 g/kg) reversed the guanabenz-evoked
      decreases in blood pressure and plasma catecholamine levels. It is concluded that
      (i) ethanol adversely interacts with centrally acting antihypertensive drugs
      through a mechanism that involves a directionally opposite effect on sympathetic
      activity, and (ii) a sympathetically mediated pressor effect of ethanol is
      enhanced in the presence of an inhibited central sympathetic tone.

PMID- 1362924
TI  - Inhibition of nitrovasodilator- and acetylcholine-induced relaxation and cyclic
      GMP accumulation by the cytochrome P-450 substrate, 7-ethoxyresorufin.
AB  - We examined the effect of the cytochrome P-450 substrate, 7-ethoxyresorufin (7
      ER), and its corresponding product, resorufin, on nitrovasodilator- and
      endothelium-dependent relaxation of isolated rat aorta. The EC50 value for
      glyceryl trinitrate (GTN) induced relaxation was increased over 100-fold by 7-ER
      and less than 3-fold by resorufin. The EC50 value for sodium nitroprusside (SNP)
      induced relaxation was increased approximately 12-fold by 7-ER, acetylcholine
      (ACh) induced relaxation was abolished, and relaxation induced by
      isopropylnorepinephrine was not significantly affected. GTN-, SNP-, and ACh
      induced increases in cyclic GMP accumulation were inhibited by 7-ER, as were
      basal cyclic GMP levels in endothelium-intact, but not endothelium-denuded
      tissues. 7-ER decreased GTN biotransformation in intact aorta and decreased the
      regioselective formation of glyceryl-1,2-dinitrate. The activation by GTN and SNP
      of aortic guanylyl cyclase in broken cell preparations was not affected by 7-ER,
      indicating that the inhibitory effect of 7-ER is probably not due to a direct
      interaction with guanylyl cyclase. The inhibitory effect of 7-ER on GTN-induced
      relaxation was not altered by the addition of superoxide dismutase, suggesting
      that 7-ER does not act by increasing superoxide anion concentration (which would
      serve to increase the degradation of nitric oxide (NO) formed during vascular GTN
      biotransformation). Our data provide further evidence for the role of the
      cytochrome P-450--cytochrome P-450 reductase system in the biotransformation of
      GTN to an activator (presumably nitric oxide) of guanylyl cyclase. The data are
      consistent with a mode of action of 7-ER involving either competitive inhibition
      of vascular cytochrome P-450 or uncoupling of vascular cytochrome P-450 reductase
      from cytochrome P-450. The data also suggest that the cytochrome P-450 system
      facilitates NO release from SNP and that 7-ER has an inhibitory effect on
      endothelial nitric oxide synthase.

PMID- 1362926
TI  - Genotyping of spinal muscular atrophy families with linked DNA probes.
AB  - We report on linkage analysis and haplotype characterization in 40 Italian
      families with spinal muscular atrophy (SMA). The investigated loci included D5S6,
      D5S112, D5S39, and D5S76. No evidence of unlinked families was found. Thirty-two
      (80%) of the examined families were fully informative for prenatal diagnosis and
      carrier detection. The frequencies of individual alleles did not differ between
      SMA and normal chromosomes.

PMID- 1362927
TI  - Peroxisome proliferators, a unique set of drug-metabolizing enzyme inducers:
      commentary on a symposium.

PMID- 1362925
TI  - A 9.6 kilobase deletion in the low density lipoprotein receptor gene in Norwegian
      familial hypercholesterolemia subjects.
AB  - Haplotype analysis of the low density lipoprotein receptor (LDLR) gene was
      performed in Norwegian subjects heterozygous for familial hypercholesterolemia
      (FH). Southern blot analysis of genomic DNA, using an exon 18 specific probe and
      the restriction enzyme NcoI, showed that two out of 57 unrelated FH subjects had
      an abnormal 3.6 kb band. Further analyses revealed that this abnormal band was
      due to a 9.6 kb deletion that included exons 16 and 17. The 5' deletion
      breakpoint was after 245 bp of intron 15, and the 3' deletion breakpoint was in
      exon 18 after nucleotide 3390 of cDNA. Thus, both the membrane-spanning and
      cytoplasmatic domains of the receptor had been deleted. A polymerase chain
      reaction (PCR) method was developed to identify this deletion among other
      Norwegian FH subjects. As a result of this screening one additional subject was
      found out of 124 subjects screened. Thus, three out of 181 (1.7%) unrelated
      Norwegian FH subject possessed this deletion. The deletion was found on the same
      haplotype in the three unrelated subjects, suggesting a common mutagenic event.
      The deletion is identical to a deletion (FH-Helsinki) that is very common among
      Finnish FH subjects. However, it is not yet known whether the mutations evolved
      separately in the two countries.

PMID- 1362928
TI  - Induction of P-450 cytochromes 2E2, 1A1, and 1A2 by imidazole in neonatal
      rabbits.
AB  - Cytochrome P-450 2E1 is induced in adult rabbits by treatment with alcohol,
      imidazole, and a variety of other agents, as shown earlier in this laboratory,
      but it is not known whether the highly homologous P-450 2E2 is similarly induced.
      In this study, the effects of imidazole on 2E2 expression were examined in
      neonatal rabbits, in which 2E1 is not detectable. Treatment of the animals with
      imidazole on days 8 through 11 after birth caused a 3-fold increase in the
      content of total P-450 in liver microsomes. In contrast, the microsomal content
      of cytochrome b5 and NADPH-P450 reductase was not changed. Immunoblot analysis
      revealed a significant increase in the level of P-450 2E2 (3-fold) as well as 1A1
      (> 10-fold) and 1A2 (> 2-fold) in hepatic microsomes from imidazole-treated
      neonatal rabbits. The rates of microsomal N-demethylation of N
      nitrosodimethylamine and O-deethylation of 7-ethoxyresorufin were similarly
      increased from 1.3 and 0.03 nmol/min/mg protein, respectively, to 5.6 and 0.24
      nmol/min/mg protein, respectively, by imidazole treatment. Blot analysis
      indicated that the levels of 2E2, 1A1, and 1A2 mRNAs are not increased by
      imidazole treatment and that 2E1 mRNA is not detectable in either untreated or
      imidazole-treated neonates. The induction of P-450 2E2 was confirmed by NH2
      terminal amino acid sequence analysis of immunopurified 2E protein from hepatic
      microsomes of imidazole-treated neonatal rabbits.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1362929
TI  - Phenobarbital and dexamethasone induce expression of cytochrome P-450 genes from
      subfamilies IIB, IIC, and IIIA in mouse liver.
AB  - Phenobarbital (PB) and dexamethasone (DEX) induce several liver-specific
      cytochrome P-450 mRNAs in rats. We examined the induction of P-450 mRNAs from
      families IIB, IIC, and IIIA by PB and DEX in six inbred mouse strains. P-450IIB1
      related mRNA species were induced 3- to 13-fold by PB and 3- to 15-fold by DEX in
      all animals. P-450IIC6-related mRNA species were induced 3- to 7-fold by PB in
      males and females, and up to 5-fold by DEX in most males but not in female mice,
      in which DEX was inactive. P-450IIIA-related mRNA species were induced 2- to 7
      fold by PB and 2- to 20-fold by DEX in all animals of either sex. In DBA/2J
      female mice, both inducers triggered a comparable early response (4 hr) at a low
      dose (10 mg/kg) for all three gene subfamilies, the maximum being reached between
      8 and 18 hr of treatment with 100 mg/kg. Under the optimal induction conditions,
      coadministration of PB and DEX did not lead to any further increase in the
      responses. These results demonstrate the existence of analogies, as well as
      striking differences in the inductive effects of PB and DEX between rats and
      mice. They also indicate the possible involvement of these inducers in related
      inductive pathways for three cytochrome P-450 gene subfamilies in mouse liver.

PMID- 1362930
TI  - Cyclosporin A metabolism in human liver, kidney, and intestine slices. Comparison
      to rat and dog slices and human cell lines.
AB  - This study assesses the contribution of cyclosporin A (CsA) metabolism at sites
      of CsA-induced toxicity: kidney and liver, and a site of absorption, the
      intestine. With organ slice cultures (8 mm phi), it has been possible to
      demonstrate that the extrahepatic metabolism of CsA is significant. Both human
      kidney and colonic mucosal tissue metabolize CsA (1 microM, 24 hr) as analyzed by
      HPLC. The major metabolite M17 was formed in the kidney at an initial rate of 3
      pmol/hr/mg slice protein, which was comparable to M17 formation in the liver
      slices (5 pmol/hr/mg slice protein). The rate of total CsA metabolism by human
      kidney slices represents about 42% the rate in liver slices. The metabolism of
      CsA to M17 was the same in the human kidney cell line 293; however, CsA
      metabolism was not detectable using human kidney microsomes, nor was metabolism
      clearly evident in either rat or dog kidney slice cultures. The metabolism of CsA
      by human colonic mucosal slices to at least three metabolites and the metabolism
      of CsA by the human intestinal cell line FHs74 Int indicates that the intestinal
      metabolism of CsA contributes to the first-pass effect of the drug. The liver
      proved to be the major site of CsA biotransformation in terms of the complexity
      of metabolites produced, whereas the human liver HepG2 cell line proved not to be
      a suitable model for CsA metabolism. A time course revealed that the first
      metabolites formed in the liver slice cultures were the monohydroxylated, M1 and
      M17, and N-demethylated, M21, followed by the secondary metabolites (including
      M8, M13, and M18).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362931
TI  - Pharmacokinetics and pharmacodynamics of valproate analogs in rats. III.
      Pharmacokinetics of valproic acid, cyclohexanecarboxylic acid, and 1-methyl-1
      cyclohexanecarboxylic acid in the bile-exteriorized rat.
AB  - The pharmacokinetics of valproic acid (VPA) and its structural analogs
      cyclohexanecarboxylic acid (CCA) and 1-methyl-1-cyclohexanecarboxylic acid (MCCA)
      were examined in bile-exteriorized rats. A 0.52 mmol/kg dose (equivalent to 75
      mg/kg VPA) of test compound (N = 4 rats per compound) was administered as an
      intravenous bolus. VPA, CCA, and MCCA concentrations in serum, bile, and urine
      were determined by gas chromatography before and after incubation in sodium
      hydroxide to hydrolyze base-labile conjugates. Concentration-time profiles of
      these compounds in serum displayed apparent Michaelis-Menten kinetics. Serum
      concentrations of base-labile conjugates were similar to parent concentrations
      for VPA, were an order of magnitude lower than parent concentrations for CCA, and
      were undetectable for MCCA. Urinary recovery of base-labile (apparently
      glucuronide) conjugates in the bile-exteriorized rat was 28.8%, 12.0%, and 25.2%
      of the administered dose for VPA, CCA, and MCCA, respectively. In contrast, more
      than 50% of the dose for VPA and MCCA was recovered in bile as the base-labile
      conjugate, with less than 5% of the CCA dose recovered via this excretory route.
      Bile flow was stimulated significantly by VPA and MCCA, but not by CCA; changes
      in bile flow correlated with the biliary excretion rate of base-labile conjugates
      rather than with excretion of the parent compounds themselves.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1362932
TI  - Metabolism of 3-tert-butyl-4-hydroxyanisole by horseradish peroxidase and
      hydrogen peroxide.
AB  - 3-Tert-butyl-4-hydroxyanisole (3-BHA) was metabolized in the presence of
      horseradish peroxidase and hydrogen peroxide to 2-tert-butyl-p-benzoquinone
      (TBQ), 2,3-epoxy-5-tert-butyl-1,4-benzoquinone (TBQ-epoxide), and two known
      dimers. The formation of TBQ from 3-BHA required both horseradish peroxidase and
      hydrogen peroxide. When 2.5 mM 3-BHA was incubated with horseradish peroxidase
      and hydrogen peroxide, the formation of TBQ increased with hydrogen peroxide
      concentration up to 5 mM and decreased gradually at higher concentrations of
      hydrogen peroxide. On the other hand, the formation of TBQ-epoxide from 3-BHA
      increased, depending on hydrogen peroxide concentration at higher concentrations
      than 1 mM. In incubating 2-tert-butylhydroquinone (TBHQ) with horseradish
      peroxidase and hydrogen peroxide, TBHQ was rapidly oxidized to TBQ, and then TBQ
      epoxide was also produced at concentrations more than 2.5 mM of hydrogen
      peroxide. In the absence of horseradish peroxidase, the incubation of TBQ with
      hydrogen peroxide resulted in TBQ-epoxide production. These results suggest that
      3-BHA is metabolized to TBHQ, which is rapidly oxidized to TBQ, by horseradish
      peroxidase and hydrogen peroxide, and then TBQ is converted to TBQ-epoxide by
      only hydrogen peroxide.

PMID- 1362933
TI  - Simultaneous modeling of the pharmacokinetic and pharmacodynamic properties of
      enalkiren (Abbott-64662, a new renin inhibitor). I: Single dose study.
AB  - This study describes the relationship between the measured effects (angiotensin I
      and renal plasma flow) and plasma drug levels using a combined pharmacokinetic
      pharmacodynamic model after 90 min iv infusion of enalkiren in 15 healthy, salt
      depleted subjects. Doses from 0.002 to 0.512 mg/kg were evaluated. One hour prior
      to enalkiren dosing, para-aminohippuric acid infusion was started for each
      subject and continued until 3 hr after the start of enalkiren infusion. Timed
      blood samples were obtained to measure enalkiren, para-aminohippuric acid, and
      angiotensin I levels in plasma. Enalkiren-induced effect changes lagged in time
      behind the plasma enalkiren level changes, showing a counterclockwise hysteresis
      loop. To relate the temporal relationship of effect changes accurately to plasma
      drug levels, a pharmacokinetic model was combined with a pharmacokinetic model
      that incorporated a hypothetical effect compartment. The magnitude of the time
      lag was quantified by the half-time of equilibration between concentrations in
      the hypothetical effect compartment and the plasma enalkiren levels (t1/2keo).
      The t1/2keo for angiotensin I (0.002 hr) is significantly shorter than that of
      renal plasma flow (0.267 hr), indicating that enalkiren equilibrates more rapidly
      with the angiotensin I-related effect compartment than the renal plasma flow
      related effect compartment. Moreover, the model allows for estimation of the
      effect site concentration that causes one-half of the maximal predicted effect
      (EC50), which is a measure of an individual's sensitivity to enalkiren. The EC50
      of angiotensin I (81.1 ng/ml) is substantially lower than that of renal plasma
      flow (4414 ng/ml), indicating that angiotensin I may be a more sensitive measure
      of enalkiren effects than renal plasma flow.

PMID- 1362934
TI  - Pharmacokinetic profile of theophylline in isolated perfused liver of rabbits at
      different ages. Development of drug-metabolizing activity during ontogenesis.
AB  - The ontogeny of the biotransformation of exogenous and endogenous compounds has
      been mostly studied using liver cells and microsomal fractions. We have used
      liver perfusion for the first time to characterize the development of the total P
      450 cytochrome-dependent system in the rabbit, with theophylline (TH) as tool
      substance. Livers of 0- to 60-day-old rabbits were perfused with TH (10
      micrograms/ml) for 3 hr. Metabolizing enzymes (cytochrome P-450), ATP,
      glutathione, and glycogen were measured in liver tissue after perfusion. Lactate
      dehydrogenase, glutamic-oxalacetic transaminase, glucose, and urea were assayed
      in the medium throughout perfusion. The pharmacokinetic profile of TH was
      determined. The activity of total cytochrome P-450, as well as the intrinsic
      unbound clearance and TH metabolites production, increased following a similar
      sigmoidal pattern and reached a plateau around 30-45 days of the postnatal
      development of rabbit liver. The perfused tissue showed no signs of age-related
      hepatic damage or toxic effects of TH. Thus, the results in perfused liver
      predict its metabolic capacity during ontogenesis.

PMID- 1362935
TI  - Stereoselective sulfoxidation by human flavin-containing monooxygenase. Evidence
      for catalytic diversity between hepatic, renal, and fetal forms.
AB  - The stereoselective formation of p-tolyl methyl sulfoxide from the corresponding
      sulfide has been examined in detergent-solubilized human adult liver, adult
      kidney, and fetal liver microsomes, in order to compare the functional activities
      of human flavin-containing monooxygenase(s). Solubilization with detergent was
      performed to eradicate the contribution that cytochrome P-450 would make to the
      net stereochemistry. Consistent with studies in experimental animal livers,
      solubilized human fetal liver and adult kidney microsomes formed (R)-p-tolyl
      methyl sulfoxide in greater than 86% enantiomeric excess. These enzyme activities
      were sensitive to methimazole inhibition and were markedly thermolabile in the
      absence of NADPH, attributes that are consistent with a flavin-containing
      monooxygenase-mediated process. However, solubilized adult human liver microsomes
      displayed little stereoselectivity (0-40% enantiomeric excess) for the formation
      of (R)-p-tolyl methyl sulfoxide, although this reaction also displayed several of
      the characteristics of a flavin-containing monooxygenase-dependent process,
      including sensitivity to methimazole inhibition and NADPH protection against heat
      inactivation. Furthermore, this lack of stereoselectivity was not attenuated by
      the inclusion of activated oxygen scavengers in reaction mixtures. Human tissue
      metabolite profiling was further studied by using the ethyl, propyl, and
      isopropyl p-tolyl sulfides. Parallel changes in product stereochemistry as a
      function of increasing steric bulk were observed with the fetal liver and adult
      kidney tissue, whereas an anomalous profile was again observed with adult human
      liver. These data are consistent with the presence of functionally discrete
      complements of the flavin-containing monooxygenase in detergent-solubilized adult
      and fetal human liver microsomes.

PMID- 1362936
TI  - Characterization of metabolites of xylazine produced in vivo and in vitro by
      LC/MS/MS and by GC/MS.
AB  - The metabolic fate of xylazine, 2-(2,6-dimethylphenylamino)-5,6-dihydro-4H-1,3
      thiazine, in horses is described. The major metabolites identified in the
      hydrolyzed horse urine were 2-(4'-hydroxy-2',6'-dimethylphenylamino)-5,6-dihydro
      4H-1,3-thiazi ne, 2-(3'-hydroxy-2',6'-dimethylphenylamino)-5,6-dihydro-4H-1,3
      thiazi ne, N-(2,6-dimethylphenyl)thiourea, and 2-(2',6'-dimethylphenylamino)-4
      oxo-5,6-dihydro-1,3-thiazine. These metabolites were also produced by incubating
      xylazine with rat liver microsomes. The major metabolite produced in vitro by rat
      liver preparations was found to be the ring opened N-(2,6
      dimethylphenyl)thiourea. The identities of these metabolites were confirmed by
      spectroscopic comparisons with synthetic standards. Phenolic metabolic standards
      were synthesized efficiently by the use of Fenton's reagent. This reagent was
      used to monohydroxylate multiply substituted aromatic ring systems. LC/MS/MS,
      with an atmospheric pressure chemical ionization source, was found to be
      particularly useful in confirming the presence of phenolic metabolites in
      hydrolyzed equine urine and microsomal extracts. These phenolic metabolites could
      not be analyzed by GC/MS even after derivatization with silylating agents. The
      advantage of LC/MS/MS was that no or little sample preparation of urine or
      microsomal extract was necessary prior to the analysis. A mechanism is also
      proposed for the formation of the major metabolite, N-(2,6
      dimethylphenyl)thiourea, from xylazine.

PMID- 1362937
TI  - Metabolism and disposition of gemcitabine, and oncolytic deoxycytidine analog, in
      mice, rats, and dogs.
AB  - Gemcitabine, 2'-deoxy-2',2'-difluorocytidine, is a broad spectrum oncolytic
      compound with antitumor activity in solid tumor models. The pharmacokinetics,
      metabolism, and disposition of gemcitabine was examined in mice, rats, and dogs.
      All three species metabolize gemcitabine by deamination to the uracil metabolite.
      However, deamination in the mouse and dog was more extensive than in the rat. The
      mouse deaminated gemcitabine rapidly with the plasma concentration maximum of the
      uracil metabolite of gemcitabine being attained at 15 min postdosing compared
      with approximately 3 and 6 hr in the dog and rat, respectively. The rapid
      deamination in the mouse was also reflected in the plasma half-life of the parent
      compound. The mouse exhibited the shortest plasma half-life, approximately 0.28
      hr, contrasted with 2.14 and 1.38 hr half-lives in rat and dog, respectively.
      Plasma AUC for the uracil metabolite of gemcitabine was 73%, 10.5%, and 315% of
      that for gemcitabine in the mouse, rat, and dog, respectively. Tissue
      concentrations of gemcitabine-derived radioactivity in the rat and mouse
      indicated that gemcitabine was rapidly distributed throughout the body. Half
      lives of radioactivity in tissues of both the rat and mouse were relatively
      short, with the longest tissue half-lives of 5.7 and 3.0 hr, respectively. Plasma
      protein binding is negligible in all three species. The major route of
      elimination is via the urine in all three species with 76-86% of the dose
      excreted in the first 24 hr. The predominant radiolabeled component isolated from
      urine was gemcitabine in the rat and its uracil metabolite in the mouse and dog.

PMID- 1362938
TI  - Pharmacokinetics of oral methamphetamine and effects of repeated daily dosing in
      humans.
AB  - The pharmacokinetics of orally administered S-(+)-methamphetamine-d3 were
      investigated in human male volunteers before and after a 13-day course of a slow
      release form of S-methamphetamine hydrochloride. A one-compartment
      pharmacokinetic model incorporating a lag time fits the data best. The average
      elimination half-life was 10.1 hr (range of 6.4-15.1 hr). There were no
      statistically significant differences in pharmacokinetic parameters when a low
      dose (0.125 mg/kg) was given before and after the 13-day oral regimen. When a
      higher challenge dose (0.250 mg/kg) was used, the maximum plasma concentration of
      methamphetamine-d3 was slightly but significantly greater when the test dose was
      given at the end of the oral dosing period than when it was given at the
      beginning. Although minor differences in pharmacokinetics occur after subchronic
      treatment with low doses of methamphetamine, their result would be to increase
      plasma concentration of the drug. Therefore, development of pharmacodynamic
      tolerance to methamphetamine could not be explained on the grounds of a change in
      pharmacokinetics.

PMID- 1362940
TI  - Specific and enantioselective sulfoxidation of an aryl-trifluoromethyl sulfide by
      rat liver cytochromes P-450.
AB  - Evidence based on thermal stability and enzyme inhibition data suggests that the
      sulfoxidation of the drug toltrazuril by rat liver microsomes is catalyzed by
      different cytochromes P-450. Pretreatment of rats by different inducers-
      phenobarbital, 3-methylcholanthrene, dexamethasone, and triacetyloleandomycin-
      results in a 2.1-, 2.6-, 2.9-, and 1.8-fold increase, respectively, in the rate
      of sulfoxidation. The highest increase (8.4-fold) was observed after treatment of
      microsomes from triacetyloleandomycin-treated animals by potassium ferricyanide.
      Castration and aging also modify the sulfoxidase activity. The relative rate of
      formation of the two toltrazuril enantiomers [(A)- and (B)-sulfoxides] depends on
      the source of the microsomes, suggesting that different cytochromes P-450 have
      different stereoselectivities.

PMID- 1362939
TI  - Pharmacokinetic analysis of the metabolism of cocaine to norcocaine and N
      hydroxynorcocaine in mice.
AB  - Cocaine is hepatotoxic in humans and is a very effective hepatotoxin in the
      mouse. Previous in vitro studies have shown that the mixed function oxidase
      system is very important in the metabolism of cocaine to the hepatotoxic species.
      Activation of cocaine to the cytotoxic species is thought to proceed through the
      N-demethylation and subsequent N-hydroxylation of the bridgehead amine. The in
      vivo metabolism of cocaine involves not only oxidative but also hydrolytic
      mechanisms. Therefore the principle aim of this study was to establish a system
      in which the in vivo metabolism of cocaine to norcocaine and N-hydroxynorcocaine
      could be determined. The in vivo metabolism of acutely administered cocaine to
      norcocaine and N-hydroxynorcocaine was assessed in two inbred mouse strains; one
      that is relatively sensitive to cocaine hepatotoxicity but shows little
      enhancement in toxicity when pretreated with phenobarbital (DBA/2lbg), and one
      that shows little hepatotoxicity unless pretreated with phenobarbital
      (C57BL/6lbg). Although no significant differences between the strains were seen
      in the pharmacokinetics of cocaine, the half-life of both norcocaine and N
      hydroxynorcocaine was significantly longer in DBA mice. Accordingly, the area
      under the curve values for hepatic norcocaine and N-hydroxynorcocaine were
      approximately 5- and 3-fold greater, respectively, in DBA as compared with C57BL
      mice. The higher levels of both norcocaine and N-hydroxynorcocaine in the DBA
      mouse are consistent with previously established differences in cocaine
      hepatotoxicity in these strains of mice. Pretreatment of C57BL mice with
      phenobarbital prolonged the half-life of norcocaine and N-hydroxynorcocaine 5- to
      8-fold over C57BL control values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362941
TI  - Microbial models of mammalian metabolism. N-dealkylation of furosemide to yield
      the mammalian metabolite CSA using Cunninghamella elegans.
AB  - Furosemide (Lasix), a widely used diuretic, is metabolized by the fungus
      Cunninghamella elegans (ATCC 36112) to 4-chloro-5-sulfamoyl anthranilic acid
      (CSA), a metabolite also present in mammalian systems. This metabolite was
      isolated following preparative-scale incubations of C. elegans, and was
      characterized by comparison with standard CSA using 13C-NMR, mass spectrometry
      (high-resolution mass spectra, electron impact mass spectra), UV, TLC, and HPLC
      with fluorescence detection. Because a known complication with furosemide studies
      is the spontaneous formation of CSA by decomposition of furosemide during
      incubation, extraction, and/or analysis, a time course study was conducted to
      determine the rate of CSA formation caused by metabolism vs. the relatively low
      rate of CSA formation caused by spontaneous decomposition.

PMID- 1362942
TI  - Role of guinea pig and rabbit hepatic aldehyde oxidase in oxidative in vitro
      metabolism of cinchona antimalarials.
AB  - Cinchona alkaloids (quinine, quinidine, cinchonine, and cinchonidine) were
      incubated with partially purified aldehyde oxidase from rabbit or guinea pig
      liver. Reversed-phase HPLC methods were developed to separate the oxidation
      products from the parent drugs, and the metabolites were identified on the basis
      of their infrared and mass spectral characteristics. All four alkaloids were
      oxidized at carbon 2 of the quinoline ring to give the corresponding lactams. In
      addition, the dihydro contaminants of the cinchona alkaloids were also
      metabolized by aldehyde oxidase to the 2-quinolone derivatives. Kinetic constants
      for the oxidation reactions were determined spectrophotometrically and showed
      that these substrates have a low affinity (KM values of around 10(-5) M) for
      hepatic aldehyde oxidase, coupled with a relatively low oxidation rate. However,
      the overall efficiency of the enzyme (Vmax/KM) toward this group of compounds
      indicates that in vivo biotransformation by aldehyde oxidase will be a
      significant pathway. Microsomal metabolites were also isolated from quinine and
      quinidine incubations with rabbit or guinea pig liver fractions. 3-Hydroxyquinine
      (quinidine) and O-desmethylquinine (quinidine) were identified in microsomal and
      10,000g supernatant extracts from quinine and quinidine, respectively. Oxidation
      of quinine via aldehyde oxidase appeared to be the predominant pathway in rabbit
      10,000g fractions, because 2'-quininone was the major metabolite under these
      conditions with lower concentrations of the microsomal metabolites produced along
      with a dioxygenated derivative thought to be 3-hydroxy-2'-quininone.

PMID- 1362943
TI  - Studies on tertiary amine UDP-glucuronosyltransferases from human and rabbit
      hepatic microsomes.
AB  - The conversion of tertiary amines to quaternary ammonium glucuronides was
      investigated in human liver microsomes, and characteristics of the UDP
      glucuronosyltransferase (UGT) catalyzing quaternary ammonium glucuronidation were
      evaluated. In addition, a rabbit liver microsomal UGT mediating this reaction was
      studied. The kinetics of quaternary ammonium glucuronidation of cyproheptadine,
      tripelennamine, amitriptyline, and doxepin in intact human liver microsomes was
      determined. Tripelennamine was found to have the lowest apparent KM and was used
      as a representative substrate for further studies. A polyclonal antibody
      preparation raised in sheep against rabbit liver p-nitrophenol UGT was found to
      inhibit tripelennamine glucuronidation in solubilized human liver microsomes, but
      had no effect on p-nitrophenol, 4-methylumbelliferone, 4-aminobiphenyl, estriol,
      morphine, or naloxone glucuronidation. This antibody also inhibited
      tripelennamine glucuronidation in solubilized rabbit liver microsomes, but had
      little or no effect on estrone, testosterone, estradiol, androsterone, and
      morphine glucuronidation. Chlorpromazine competitively inhibited tripelennamine
      glucuronidation. This inhibition was markedly enhanced by UV light irradiation.
      [3H] Chlorpromazine binding to solubilized human liver microsomes was also
      increased by UV light. The binding was antagonized by substrates for tertiary
      amine UGT but not by substrates for morphine UGT. These studies suggest that the
      tertiary amine UGT is photo-affinity-labeled by chlorpromazine. Furthermore, it
      would appear from immunoinhibition and [3H]chlorpromazine labeling experiments
      that tertiary ammonium glucuronidation is catalyzed by a unique and distinct UGT
      in rabbit and human liver microsomes.

PMID- 1362944
TI  - Substrates for microsomal azoreductase. Hammett substituent effects, NMR studies,
      and response to inhibitors.
AB  - In previous studies on azoreduction by microsomal cytochrome P-450, we identified
      two classes of substrates structurally related to 4-dimethylaminoazobenzene. Both
      require polar electron-donating groups for binding to enzyme and are
      differentiated by their structure, their redox potentials, their rates of
      chemical and enzymic reduction, and the influence on their metabolism of inducing
      agents, CO and O2. Azo compounds whose reductions are insensitive to CO and O2 (I
      substrates) contain electron-donating substituents on either ring. Azo compounds
      whose reductions are O2- and CO-sensitive (S-substrates) also contain electron
      withdrawing groups on the opposite (prime) ring. For all dyes, NMR studies
      revealed minor differences in the chemical shifts of the protons attached to the
      phenyl ring substituted with electron-donating substituents (ring A). This is
      consistent with the narrow range of pKa's (basicity) and KM values for all
      substrates. However, there are significant differences in the chemical shifts of
      the aromatic protons of the prime ring (ring B). The difference in chemical
      shifts is most pronounced for aromatic protons adjacent to the prime ring
      substituents, showing a clear distinction between I and S substrates.
      Furthermore, the Hammett sigma substituent constants on the prime ring clearly
      distinguish between the two classes of dyes. I- and S-substrates have negative
      and positive sigma Hammett values, respectively. This implies that the mechanism
      of microsomal azoreduction is critically dependent on the charge and redox
      potentials of the dyes and is exclusively determined by the nature of the
      substituents on the prime ring.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362945
TI  - Pharmacokinetics of D(+)-usnic acid in rabbits after intravenous and oral
      administration.
AB  - The pharmacokinetics of D(+)-usnic acid--a lichen antitubercular, antitumor, and
      enzyme-inhibiting agent--was studied in rabbits following intravenous or oral
      administration of 5 and 20 mg/kg body weight doses, respectively. Plasma samples
      were collected at different time intervals, and usnic acid was determined by
      HPLC. Plasma usnic acid levels following intravenous administration showed a
      triexponential elimination with a mean +/- SD terminal half-life of 10.7 +/- 4.6
      hr. The volume of distribution of the central compartment and systemic clearance
      were 43.9 +/- 21.3 ml/kg and 12.2 +/- 3.0 ml/hr/kg, respectively. Pharmacokinetic
      parameters obtained, based on compartmental and noncompartmental approaches, were
      comparable. Plasma concentration data obtained after oral administration were
      analyzed using a noncompartmental method. Peak plasma level (Cmax) of 32.5 +/-
      6.8 micrograms/ml was achieved in 12.2 +/- 3.8 hr (tmax). Mean absolute
      bioavailability of usnic acid following oral administration was 77.8%.

PMID- 1362946
TI  - Oxidation of carbovir, a carbocyclic nucleoside, by rat liver cytosolic enzymes.
      Enantioselectivity and enantiomeric inhibition.
AB  - Previous metabolism studies of (-)-cis-carbovir (1'R-cis-2-amino-1,9-dihydro-9
      [4'S-hydroxymethyl-2-cyclopenten-1- yl]-6H- purin-6-one), an antiviral agent,
      have shown that the major route of metabolism of carbovir in the rat is oxidation
      of the methylene hydroxyl group of the cyclopentadiene ring to form the
      corresponding 4'-carboxylic acid metabolite. We have determined that rat hepatic
      alcohol dehydrogenase and aldehyde dehydrogenase are responsible for this
      biotransformation through sequential oxidation of the alcohol through the
      aldehyde to the carboxylic acid. The results of incubations of racemic (+/-)-cis
      carbovir with rat liver cytosol showed that this oxidation occurs
      enantioselectively favoring the (+)-enantiomer by a factor of 6- to 7-fold. We
      have proven that alcohol dehydrogenase contributes to the enantioselectivity of
      the overall oxidation process, but were unable to determine whether or not any
      contribution is made by aldehyde dehydrogenase. Parallel incubations conducted
      with the separate enantiomers revealed that the concentration required to achieve
      a half-maximal rate for the oxidation of the (+)-enantiomer (0.27 mM) was one
      fifth that required for the (-)-enantiomer (1.36 mM). Results from enantiomeric
      inhibition studies showed that (+)-carbovir inhibited the oxidation of (-)
      carbovir. In contrast, (-)-carbovir did not inhibit the oxidation of (+)
      carbovir.

PMID- 1362947
TI  - Disposition and metabolism of triprolidine in mice.
AB  - The disposition of the antihistamine, triprolidine, was studied in male and
      female CD-1 mice after a single oral 50 mg/kg dose of [14C]triprolidine HCl.
      Urine and feces collected over 72 hr postdosing were analyzed for total
      radiocarbon, and for parent drug and metabolites by radiochromatography.
      Structures of metabolites were determined by GC/MS, direct probe MS, FAB/MS,
      LC/MS, NMR, and IR techniques. More than 80% of the dose was recovered in the
      urine, with the remainder recovered in the feces. The carboxylic acid analog of
      triprolidine (219C69) was found to be the major metabolite in urine and feces,
      accounting for an average of 57.6% of the administered dose. Three minor
      metabolites were identified as a gamma-aminobutyric acid analog of triprolidine,
      a pyrrolidinone analog of 219C69, and a pyridine-ring hydroxylated derivative of
      triprolidine. Parent drug could only be detected in urine and accounted for 0.3%
      (females) to 1.1% (males) of the dose. The results of this study showed that
      triprolidine was absorbed well but extensively metabolized when administered
      orally to mice.

PMID- 1362949
TI  - Clinical pharmacology of combined oral uracil and ftorafur.
AB  - Phase I clinical trials of the combination of oral uracil with ftorafur (Ft) were
      conducted in patients with solid tumors over either a 5-day (345 mg/m2/day) or a
      28-day (160 mg/m2/day) period. The uracil dose, which was four times the Ft dose
      (molar basis), was previously shown to be optimal at inhibiting the degradation
      of 5-fluorouracil (5-FU). Pharmacology was performed on the first dose of the
      first day of therapy. Ft was measured by HPLC, whereas uracil and 5-FU were
      measured using GC/MS. Plasma levels were highest for Ft, followed by uracil and 5
      FU at all time points. Peak and trough levels after selected subsequent doses
      were also measured; these varied in the individual from day to day. Maximum
      plasma levels (Cpmax) for Ft, uracil, and 5-FU except in one patient were
      achieved at 0.6-2.1 hr, 0.6-4.1 hr, and 0.7-2.0 hr, respectively. Generally,
      lower doses yielded more rapid decay of 5-FU and uracil levels than did higher
      doses. No correlation was observed between myelotoxicities (granulocytopenia and
      leukopenia) and the Cpmax and AUC0-6hr of Ft (p > 0.2). However, after the
      highest uracil and Ft dose (approximately 300 mg/m2/Ft study dose), the Cpmax and
      AUC0-6hr values of 5-FU revealed significant differences (p < 0.05) in three
      patients each with and without myelotoxicity. These associations were similarly
      observed with uracil. Our findings thus indicate that measuring plasma uracil and
      more importantly, the 5-FU levels, may predict hematological toxicity and enable
      subsequent dose adjustments.

PMID- 1362948
TI  - Disposition of triprolidine in the male beagle dog.
AB  - Three male beagle dogs were given 2.5 mg/kg doses of [14C]triprolidine HCl
      monohydrate (2.09 mg/kg of the free base) by intravenous and oral routes, in a
      nonrandomized cross-over experiment. After either route of administration,
      approximately 75% of the dose was excreted in the urine, and the remainder was
      excreted in the feces. Triprolidine was extensively metabolized, with less than
      1% of the parent drug recovered in the excreta after either route of
      administration. Three metabolites were isolated from excreta and identified,
      including the major metabolite (metabolite 1, 219C69), in which the toluene ring
      methyl group was oxidized to a carboxylic acid, a metabolite (metabolite 2) in
      which the pyrrolidine ring was opened with oxidation of the terminal carbon to a
      carboxylic acid (a gamma-aminobutyric acid), and a metabolite (metabolite 3) that
      was a pyrrolidinone derivative of 219C69. Other metabolites in urine and feces
      were present in amounts too small for quantitation or identification. Route of
      administration had little effect on the metabolic pattern of triprolidine. Thus,
      after oral administration of triprolidine, a mean of 49.1% of the dose was
      excreted as 219C69, 12.0% as metabolite 2, 3.4% as metabolite 3, and 0.6% as
      triprolidine, while after intravenous administration, a mean of 50.8% of the dose
      was excreted as 219C69, 11.1% as metabolite 2, 4.2% as metabolite 3, and 0.8% as
      triprolidine. Plasma contained triprolidine, 219C69, and metabolite 2, as well as
      other apparent metabolites that were present at levels too low for quantitation.
      Mean pharmacokinetic parameters calculated for triprolidine after intravenous
      dosing were: CL = 24.4 ml/min/kg, Vdss = 5.8 liters/kg, and Vc = 1.6
      liters/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362951
TI  - Oxidation of aldose reductase inhibitors ALO-4114 and ALO-3152 catalyzed by liver
      microsomes.
AB  - Rat and Cynomolgus monkey liver microsomes catalyze the oxidation of 2.7-difluoro
      4.5-dimethoxyspiro (9H-fluorene-9,4'-imidazolidine)-2',5'-dione (ALO-4114) to its
      monomethoxymetabolite (ALO-4417). Formation of this product by O-demethylation of
      ALO-4114 is catalyzed by NADPH and oxygen-dependent microsomal enzymes with the
      properties of P-450 monooxygenases. The reaction is blocked by inhibitors
      selective for these enzymes and activity increases about 2-fold in rats
      pretreated with phenobarbital or methylcholanthrene. The increase in the O
      demethylation of ALO-4114 was, however, considerably less than the increase in
      benzphetamine N-demethylation or nitrophenetole O-deethylation activities in
      liver microsomes from rats pretreated with either phenobarbital or
      methylcholanthrene. Rats pretreated with 20 or 40 mg/kg of ALO-4114 for 3-4 days
      failed to change significantly the rate of ALO-4114 O-demethylase activity of
      liver microsomes. O-Demethylation of the achiral ALO-4114 yields the chiral ALO
      4417. The enantiomers separated on a Daicel Chiracel AS column by HPLC indicated
      that O-demethylation of ALO-4114 by microsomes from untreated rats was only
      slightly stereoselective. However, rats pretreated with methylcholanthrene not
      only enhanced activity, but also increased the formation of one enantiomer.
      Further oxidative metabolism of the enantiomers was slow and barely detectable in
      vitro. Studies conducted with Cynomolgus monkey liver microsomes from one male
      and one female per experimental group were generally consistent with those from
      the rat, but some differences were noted. Whether the differences are real or
      only reflect individual variations caused by the small sample size is not known
      at present.

PMID- 1362950
TI  - Investigation of conjugated metabolites of 4-hydroxyandrost-4-ene-3,17-dione in
      patient urine by liquid chromatography-atmospheric pressure ionization mass
      spectrometry.
AB  - Metabolism of the anticancer drug 4-hydroxyandrost-4-ene,3,17-dione (4OHA) was
      studied in cancer patients by HPLC-MS-MS. 40HA was administered orally to a
      breast cancer patient. The drug was extensively metabolized and was excreted in
      the urine as the 4OHA-glucuronide, 3 alpha-hydroxy-5 beta-androstan-4,17-dione (3
      alpha OHA)-sulfate (or 4-hydroxytestosterone-sulfate) and 3 alpha,17-dihydroxy-5
      beta-androstan-4-one (3,17-OHA)-sulfate conjugates in the 4 hr posttreatment
      sample. Other metabolites include 4OHA-sulfate, 3 alpha OHA-glucuronide, and 3,17
      OHA-monoglucuronide. When 4OHA was given to the prostatic cancer patients
      intramuscularly, different metabolites were observed as compared with the female
      studies. The most noticeable difference is the absence of 4OHA-sulfate in both 24
      and 48 hr posttreatment urine samples. The drug was eliminated mainly as 4OHA
      glucuronide, 3 alpha OHA-sulfate, and 3,17-OHA-monosulfate. Other metabolites
      that have been detected include 3 alpha OHA-glucuronide, 3,17-OHA-glucuronide,
      3,17-OHA-disulfate, and an unknown metabolite. The variation observed in
      metabolism could be attributed to a different route of drug administration (oral
      and intramuscular) and sex difference among the patients. This study describes
      the utilization of HPLC-MS-MS for monitoring the 4OHA conjugates and provides the
      first evidence of the presence of 4OHA-sulfate and its analogs in patient urinary
      extracts.

PMID- 1362952
TI  - Disposition of the human immunodeficiency virus Tat inhibitor, Ro 5-3335, in rats
      and dogs.

PMID- 1362953
TI  - Formation of indenesulfonylureas in the metabolism of the anticancer agent
      sulofenur in rats, monkeys, and humans.

PMID- 1362955
TI  - 1st European Workshop in Aviation Cardiology. Herts, United Kingdom, 10-12
      October 1991.

PMID- 1362954
TI  - Covalent binding of etodolac acyl glucuronide to albumin in vitro.

PMID- 1362957
TI  - Long-term hemopoietic repopulation by Thy-1lo, Lin-, Ly6A/E+ cells.
AB  - Murine bone marrow Thy-1lo, Lin-, Ly6A/E+ cells have been isolated by
      fluorescence-activated cell sorting (FACS). This population contained up to 27%
      in vitro colony-forming cells (CFC) when stimulated by interleukin 3 (IL-3) and
      5% day-12 spleen colony-forming units (CFU-S) (uncorrected for seeding
      efficiency). As few as 100 cells were able to reconstitute the myeloid and
      lymphoid compartments of lethally irradiated recipients for periods of up to 72
      weeks. Over the range of 30-560 transplanted cells, three patterns of engraftment
      were observed; the proportion of donor cells increased gradually to values of >
      90%, gradually declined, or remained static over the 72-week observation period.
      When the donor cell percentage in the peripheral blood exceeded 60%, both myeloid
      (neutrophils and monocytes) and lymphoid (T- and B-lymphocytes) cells were of
      donor origin. Primary animals containing > 60% donor cells in their peripheral
      blood were able to engraft secondary recipients with donor cells of both myeloid
      and lymphoid lineages. Primary animals with < 20% donor cells in their peripheral
      blood contained bone marrow cells that were only able to produce lymphoid cells
      in the peripheral blood of secondary recipients. With > 90% of animals, including
      both primary and secondary recipients, there were no large fluctuations in the
      proportion of donor myeloid or lymphoid cells in the peripheral blood. Where
      changes occurred, with three exceptions, these were gradual. These data suggest
      that the Thy-1lo, Lin-, Ly6A/E+ population is heterogeneous and contains in vitro
      CFC, day-12 CFU-S, and long-term repopulating cells for both the myeloid and
      lymphoid lineages and cells capable of long-term repopulation of only the
      lymphoid lineage.

PMID- 1362956
TI  - The systemic availability of oral glutathione.
AB  - When the plasma glutathione concentration is low, such as in patients with HIV
      infection, alcoholics, and patients with cirrhosis, increasing the availability
      of circulating glutathione by oral administration might be of therapeutic
      benefit. To assess the feasibility of supplementing oral glutathione we have
      determined the systemic availability of glutathione in 7 healthy volunteers. The
      basal concentrations of glutathione, cysteine, and glutamate in plasma were 6.2,
      8.3, and 54 mumol.l-1 respectively. During the 270 min after the administration
      of glutathione in a dose of 0.15 mmol.kg-1 the concentrations of glutathione,
      cysteine, and glutamate in plasma did not increase significantly, suggesting that
      the systemic availability of glutathione is negligible in man. Because of
      hydrolysis of glutathione by intestinal and hepatic gamma-glutamyltransferase,
      dietary glutathione is not a major determinant of circulating glutathione, and it
      is not possible to increase circulating glutathione to a clinically beneficial
      extent by the oral administration of a single dose of 3 g of glutathione.

PMID- 1362958
TI  - Cerebral protection by AMPA- and NMDA-receptor antagonists administered after
      severe insulin-induced hypoglycemia.
AB  - Excitatory amino acids are implicated in the development of neuronal cell damage
      following periods of reversible cerebral ischemia or insulin-induced hypoglycemic
      coma. To explore the importance of glutamate receptor activation in the
      posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe
      hypoglycemia. The rats were treated immediately after the hypoglycemic insult
      with four regimes of glutamate receptor antagonists: (1) the AMPA (alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propriate)-receptor antagonist NBQX [2.3-dihydroxy-6
      nitro-7-sulfamoyl-benzo (F) quinoxaline] given as a bolus dose of 30 mg.kg-1
      i.p., followed by an i.v. infusion of 225 micrograms.kg-1.min-1 for 6 h; (2) the
      non-competitive NMDA-receptor antagonist, dizocilpine (MK-801) 1 mg.kg-1 given
      i.v.; (3) a combined NBQX treatment, (a bolus dose of 10 mg.kg-1 i.p., followed
      by an i.v. infusion of 225 micrograms.kg-1.min-1 for 6 h), with dizocilpine 0.33
      mg.kg-1 given twice i.p. at 0 and 15 min after recovery and (4) the competitive
      NMDA-receptor blocker CGP 40,116 [D-(E)-2-amino-4-methyl-5-phosphono-3- pentenoic
      acid] 10 mg.kg-1 given i.p. In the striatum, all glutamate receptor blockers
      significantly decreased neuronal damage by approximately 30%. An approximately
      50% decrease in neuronal damage was demonstrated in neocortex and hippocampus
      following the combined treatment with NBQX and dizocilpine, while protection was
      variable following the treatment with a single glutamate-receptor
      antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1362960
TI  - [Villous tumors of the Wirsung's duct and pancreatic intraductal adenocarcinoma:
      interrelation or accidental association?].
AB  - Villous neoplasms of the main pancreatic duct are uncommon. Two cases of neoplasm
      of the main cephalic pancreatic duct in 61- and 42-year-old patients presenting
      with long standing (10 and 12 years) history of abdominal pain are reported. In
      both cases, duodenal fistula was present and mucus was observed by endoscopy at
      the fistula and major papilla levels. Endoscopic retrograde pancreatography
      showed a stricture of the main pancreatic duct in the pancreatic head. In one
      case, with incomplete stricture, pancreatic ducts disclosed typical features of
      chronic obstructive pancreatitis and contained mucus casts. Histologic
      examination of total and proximal duodenopancreatectomy showed a villous
      neoplastic pattern with focal malignant changes within the main pancreatic duct.
      The adjacent pancreatic tissue showed signs of stromal invasion without lymph
      node or nervous infiltration. Glandular parenchyma was atrophic in the pancreatic
      body and tail, with extensive fibrosis, and the pancreatic duct depicted signs of
      nonpapillary hyperplasia. Histochemical study disclosed a predominant sialomucin
      secretion by villous adenoma and sulfomucin secretion by epithelial cells lining
      the accessory or main caudal pancreatic ducts. These results lead us to suggest a
      possible relationship between villous adenoma of ducts and pancreatic
      adenocarcinoma.

PMID- 1362961
TI  - DNA profiling in a genetically isolated population using three hypervariable DNA
      markers.
AB  - We determined the allele frequencies for three hypervariable DNA loci D2S44, D1S7
      and D7S21 using the probes YNH24, MS1 and MS31 in the genetically isolated
      Finnish population. The allelic length ranges were 1.7- < 6.0 kb for YNH24, 1.7-
      < 18.0 kb for MS1 and 3.2- < 12.0 kb for MS31. High heterozygosity rates (0.94
      0.96) were detected for all three probes. In 48 mother-child pairs no mutations
      were found using the probes YNH24 and MS31, whereas a mutation rate of 0.064 was
      observed for probe MS1. In addition, an unexpected four-band pattern was detected
      in 1 out of 170 individuals using the probe MS1, suggesting complex DNA
      polymorphism based on both a variable number of tandem repeats and restriction
      site polymorphism. Our findings also show that all three probes are valuable in
      individual identification in this genetically isolated population.

PMID- 1362959
TI  - An analysis of adrenergic influences on the sural-gastrocnemius reflex of the
      decerebrated rabbit.
AB  - The sural-gastrocnemius reflex was observed in decerebrated rabbits during
      intrathecal application of four alpha-adrenoceptor antagonists. Idazoxan and
      yohimbine, which are antagonists at the alpha 2-receptor, caused facilitation of
      the reflex, although idazoxan was more potent and produced a larger overall
      increase in the reflex response. However, when given after yohimbine, idazoxan
      elicited no further increase in reflex responses. The differences between the two
      drugs may result from the interaction of yohimbine with receptors for 5
      hydroxytryptamine. The selective alpha 1-receptor antagonist prazosin had no
      consistent effects when given alone, but reduced the facilitatory effects of
      idazoxan. The putative selective post-junctional alpha 2-receptor blocker SK&F
      104078 had no significant effects when given alone, nor did it influence the
      facilitatory action of a subsequent dose of idazoxan. Section of the spinal cord
      in the presence of idazoxan always caused a decrease in gastrocnemius responses
      to sural nerve stimulation. These data show that the facilitatory effects of
      idazoxan are almost certainly mediated at the spinal cord and that they do not
      involve blockade of alpha 1-receptors. It appears that idazoxan acts by blockade
      of adrenergic descending inhibition in combination with increased descending
      facilitation. The inhibition is probably mediated through noradrenaline acting at
      alpha 2-receptors, and the facilitation may be the result of release of
      noradrenaline (acting at alpha 1-receptors) and 5-hydroxytryptamine in the spinal
      cord.

PMID- 1362963
TI  - Mobilization of circulating haemopoietic cells (blood stem cells) by GM-CSF in
      patients with malignancies.
AB  - Autologous reinfusion of circulating haemopoietic progenitor and stem cells
      (blood stem cell transplantation) has emerged as an alternative to autologous
      bone marrow transplantation in a variety of malignant diseases. Major obstacles
      associated with harvest of blood stem cells by leukapheresis are: 1. relatively
      high costs, and 2. discomfort caused to the patient, as generally five to ten
      settings of leukapheresis are necessary to harvest a number of blood stem cells
      sufficient for haemopoietic restitution following myeloablative therapy. GM-CSF
      recently has been shown to effectively increase circulating haemopoietic cells,
      when given subsequent to even highly-toxic therapy. This report summarizes our
      data on mobilization of blood stem cells by GM-CSF cells in multiple myeloma
      patients.

PMID- 1362962
TI  - The effect of Mycobacterium tuberculosis on the susceptibility of human cells to
      the stimulatory and toxic effects of tumour necrosis factor.
AB  - It has previously been shown that the inherently tumour necrosis factor-alpha
      (TNF-alpha)-sensitive L929 murine fibroblast cell line becomes much more
      sensitive to the cytotoxic effect of this cytokine after exposure to
      Mycobacterium tuberculosis in culture. In this study it is now shown that normal
      human cells of types likely to be involved in tuberculous lesions are affected in
      a similar way. Growth of normal human fibroblasts is usually stimulated by TNF
      alpha in vitro, but after exposure to M. tuberculosis or to extracts of this
      organism, these cells are killed rather than stimulated by subsequent exposure to
      TNF-alpha. Similarly, human endothelial cells become susceptible to doses to TNF
      alpha which do not normally affect viability. Moreover this enhancement of
      sensitivity to TNF-alpha is not confined to its toxicity. Endothelial cells and
      HeLa cells exposed to M. tuberculosis express increased levels of ICAM-1 after
      subsequent exposure to TNF-alpha, implying synergy between the two stimuli. It is
      suggested that these effects contribute to the ability of M. tuberculosis to
      distort the normal protective role of TNF-alpha so that the cytokine becomes
      detrimental to the host.

PMID- 1362964
TI  - Liquid chromatographic purification and detection of anabolic compounds.
AB  - The role of liquid chromatography within methods of analysis for steroids,
      related compounds and beta-agonists in biological samples is discussed. Special
      attention is given to the application of liquid chromatography in sample
      preparation and extract clean-up. Different forms of liquid chromatography,
      including immunoaffinity chromatography, are compared and evaluated. Methods for
      confirmation based on gas chromatography-mass spectrometry and cryotrapping
      Fourier transform infrared spectrometry are discussed.

PMID- 1362965
TI  - Determination of tranquilisers and carazolol residues in animal tissue using high
      performance liquid chromatography with electrochemical detection.
AB  - A multi-residue method for the determination of tranquiliser residues in animal
      tissue is described. The procedure may be used to determine residues of the
      tranquilisers acepromazine, azaperone, chlorpromazine, haloperidol,
      propionylpromazine, xylazine, the metabolite of azaperone, azaperol, and the beta
      adrenoreceptor blocking agent carazolol. Existing methods of analysis for
      tranquilisers are based on ultraviolet and fluorescence detection and have been
      used for pig kidney analysis. Determination in this method was by high
      performance liquid chromatography with electrochemical detection in the screen
      mode. The enhanced selectivity offered by the electrochemical detector allowed
      determination in liver extracts, which often give rise to more interferences on
      chromatographic traces when using conventional methods of detection. The method
      offers up to a ten-fold improvement in limits of determination over methods using
      ultraviolet and fluorescence detection. Recoveries and coefficients of variation
      have been determined in the range 2-25 micrograms/kg in pig kidney and liver.
      This electrochemical detection method has been used to measure residues in
      routine surveillance programmes.

PMID- 1362966
TI  - [Pharmacology of cellular ischemia].
AB  - Knowledge of cellular disturbances provoked by an ischemic aggression conditions
      the use of a pharmacologic strategy that could possibly protect the cell from
      necrosis. Whatever the type of cell, the basic mechanisms are very similar:
      energy failure, acidosis, loss of electrolytic homeostasis, particularly of
      calcium, formation of free radicals and, of more recent knowledge, genetic
      induction. Different molecules have been shown to be effective at each of these
      stages in one or other of the many experimental models available. The therapeutic
      approach is not very forthcoming at present but the field of applications is
      vast. Ischemic disease is not restricted to cerebral or cardiac ischemia and,
      although the lesions are mainly those of senescence, it is observed in other
      etiologic frameworks, if only in the perinatal period. Finally, the great
      increase in the use of organ transplants opens up another field of application
      with research on the best method for organ preservation and optimization of its
      acceptance by the host organism.

PMID- 1362967
TI  - Comparative study of the H2-receptor antagonists cimetidine, ranitidine,
      famotidine and nizatidine on the rabbit stomach fundus and sigmoid colon.
AB  - The H2-receptor antagonists, cimetidine, ranitidine, famotidine and nizatidine,
      were tested for their effect on the isolated smooth muscle strips from the rabbit
      stomach fundus and sigmoid colon. These H2-receptor antagonists were found to
      possess a concentration-dependent contractile effect on the above smooth muscle
      preparations and the order of potency was: ranitidine = nizatidine > famotidine >
      cimetidine. In addition, the smooth muscle preparations from the sigmoid colon
      were significantly more sensitive to the above compounds than the smooth muscle
      preparations from the stomach fundus.

PMID- 1362968
TI  - Studies on the anti-allergic mechanism of glucocorticoids in mice.
AB  - Glucocorticoids inhibit IgE antibody-mediated passive cutaneous anaphylaxis (PCA)
      and chemical mediator-induced cutaneous reactions elicited in the mouse ear. In
      the present study, we investigated the effect of actinomycin D, a protein
      synthesis inhibitor, on dexamethasone-caused inhibition of PCA and histamine
      induced cutaneous reaction in the mouse ear. Tyrosine aminotransferase (TAT)
      activity in the liver, which was estimated as an index for protein synthesis,
      significantly increased by the administration of hydrocortisone, prednisolone and
      dexamethasone. Significant increase in TAT activity was observed from 2 h after
      glucocorticoid administration and peaked at 4 h, and declined gradually
      thereafter. Cycloheximide even at high doses of 100 and 300 mg/kg failed to
      affect the increase in TAT activity by dexamethasone. On the contrary,
      actinomycin D at doses of 1 and 10 mg/kg abrogated the TAT activity increase by
      dexamethasone almost completely. Treatment with 1 mg/kg of actinomycin D,
      however, failed to affect the inhibition of PCA and histamine-induced cutaneous
      reaction by dexamethasone. These results suggest that glucocorticoids exhibit
      their inhibitory action of PCA and chemical mediator-induced cutaneous reactions
      in mice through a mechanism resistant to actinomycin D treatment.

PMID- 1362970
TI  - [Nursing positively has its place].

PMID- 1362969
TI  - Richner-Hanhart syndrome (oculocutaneous tyrosinaemia, tyrosinaemia type II)

PMID- 1362971
TI  - A method to simultaneously investigate histamine-induced cyclic AMP and
      aminopyrine accumulation in isolated gastric mucosal cells from human biopsies.
AB  - A method has been developed to simultaneously measure two parameters of histamine
      induced gastric secretion, cyclic AMP and aminopyrine accumulation, in gastric
      mucosal cells from human biopsies. Histamine stimulated cyclic AMP and
      aminopyrine accumulation with different time courses. Cyclic AMP production
      reached a maximum at 30 min, whereas maximal aminopyrine accumulation was
      obtained after the cells had been incubated for 90 min in presence of 100 mcM
      histamine. Histamine was more potent in stimulating aminopyrine than cyclic AMP
      accumulation. The ED50 values for histamine-induced aminopyrine accumulation were
      estimated to be 0.88 +/- 0.02 and 25.53 +/- 8.75 mcM for cyclic AMP production,
      respectively. The aminopyrine accumulation was more than half-maximally increased
      at 1 mcM histamine without significant effects on the cyclic AMP basal level. It
      remains to be elucidated whether this finding indicates, besides cyclic AMP, the
      involvement of calcium in histamine stimulus. The histamine H2-receptor
      antagonists cimetidine and ranitidine inhibited both in vitro parameters, whereas
      the gastric proton pump inhibitor omeprazole only affected aminopyrine
      accumulation. Our method might be a valuable tool for in vitro pharmacological
      and clinical investigations on histamine-induced gastric secretion in human
      biopsies.

PMID- 1362972
TI  - Possible role of histamine in pathogenesis of autoimmune diseases: implications
      for immunotherapy with histamine-2 receptor antagonists.
AB  - The immunosuppressive chemical drugs cyclosporine A (CsA) and methotrexate (Mx)
      have recently been shown to be of benefit in several different diseases of
      autoimmune origin. Cellular immune responses may play a major role in
      autoimmunity as autoreactive T lymphocytes appear to recognize autoantigens and
      major histocompatibility complex (MHC) class II restriction molecules presented
      by non-immune, aberrant cells, subsequently leading to damage on healthy tissues.
      Psoriasis is suggested to be an autoimmune disease and in severe, uncontrollable
      psoriasis CsA and Mx are of value in reducing disease activity. Histamine is
      suggested to be involved in the pathogenesis of psoriasis and the histamine-2
      receptor antagonist ranitidine has been shown to be of value to reduce severe
      psoriatic disease. The finding that CsA and Mx efficiently reduce histamine
      formation and release raises the possibility, that histamine is one of the
      molecules involved in pathogenesis of autoimmune diseases. T cell mediated
      regulation and suppression of autoreactive T cells seem to be ineffective in
      controlling the enhanced immune reaction in patients where the discrimination
      between self and non-self is changed. A consequence of this may be induction of
      interferon-gamma (IFN-g) production and release by cytotoxic T cells,
      subsequently leading to expression of MHC II molecules on non-immune tissues. As
      immunotherapy may be of value in some autoimmune diseases the use of histamine-2
      receptor antagonists should be evaluated in patients where conventional therapy
      is ineffective to reduce disease activity.

PMID- 1362975
TI  - [Study of the recovery rate of non-NMDA desensitized receptors of hippocampal
      neurons using paired and rhythmic application of glutamate].
AB  - The new technique has been used to realize paired short-term application of
      glutamate to whole dialyzed neuron. Desensitization of receptors via first
      application of glutamate resulted in incomplete recovery of the current evoked by
      the second application if interval between both applications was less than 160
      ms. The recovery time constant of the current was found to be 44 ms at single
      exponential approximation. It is close to the mean desensitization time constant
      of the current evoked by single prolonged application of glutamate. Rhythmic
      application of glutamate resulted in a rapid fall of the mean current amplitude
      at frequencies over 10 Hz. Data obtained by the authors confirm the known concept
      of desensitization of non-NMDA receptors as a relatively slow conformation of the
      receptor-channel complex.

PMID- 1362974
TI  - [Role of glutamate intracortical connections in conditioned reflex activity].
AB  - The effects of iontophoretic application of glutamate and its blockers on
      neuronal activity of the sensorimotor cortex were studied in cat during
      fulfillment of conditioned instrumental placing reflex. 64 neurons were
      investigated. Application of glutamate caused reliable facilitation of neuronal
      impulse reactions to the conditioned stimulus. The facilitation appeared some
      seconds after beginning of the application of glutamate and continued for 5-10
      min after cessation of the iontophoretic application. The similar inhibitory
      effect in neuronal activity was observed with application of APV, kinurenate,
      ketamine. It is suggested that the NMDA receptors under natural conditions take
      part in facilitation of the synaptic transmission in glutamatergic intracortical
      pathways.

PMID- 1362973
TI  - Genetic and physical analysis of the rice bacterial blight disease resistance
      locus, Xa21.
AB  - Nearly isogenic lines (NILs) of rice (Oryza sativa) differing at a locus
      conferring resistance to the pathogen Xanthomonas oryzae pv. oryzae were surveyed
      with 123 DNA markers and 985 random primers using restriction fragment length
      plymorphism (RFLP) and random amplified polymorphic DNA (RAPD) analysis. One
      chromosome 11 marker (RG103) detected polymorphism between the NILs that
      cosegregated with Xa21. All other chromosome 11 DNA markers tested were
      monomorphic between the NILs, localizing the Xa21 introgressed region to an 8.3
      cM interval on chromosome 11. Furthermore, we identified two polymerase chain
      reaction (PCR) products (RAPD2148 and RAPD818) that detected polymorphisms
      between the NILs. Genomic sequences hybridizing with RAPD818, RAPD248 and RG103
      were duplicated specifically in the Xa21 NIL. All three markers cosegregated with
      the resistance locus, Xa21, in a F2 population of 386 progeny. Based on the
      frequency with which we recovered polymorphic Xa21-linked markers, we estimated
      the physical size of the introgressed region to be approximately 800 kb. This
      estimation was supported by physical mapping (using pulsed field gel
      electrophoresis) of the sequences hybridizing with the three Xa21-linked DNA
      markers. The results showed that the three Xa21-linked markers are physically
      close to each other, with one copy of the RAPD818 sequences located within 60 kb
      of RAPD248 and the other copy within 270 kb of RG103. None of the enzymes tested
      generated a DNA fragment that hybridized with all three of the markers indicating
      that the introgressed region containing the resistance locus Xa21 is probably
      larger than 270 kb.

PMID- 1362977
TI  - Critique, resistance, and action: working papers in the politics of nursing. 2nd
      Annual Conference on Critical and Feminist Perspectives in Nursing. Toledo, Ohio,
      February 1991.

PMID- 1362976
TI  - No constant relationship between islet amyloid polypeptide (IAPP) and insulin
      expression in insulinomas.
AB  - The relationship between insulin and islet amyloid polypeptide (IAPP) expression
      was studied at the level of RNA and peptide in 3 patients operated on for
      insulinoma. Two patients had a solitary tumour; one patient suffered from the MEN
      I syndrome. In the 3 tumours, as in normal pancreas, the same 2 IAPP-specific
      mRNA species, approximately 1600 and 2100 nucleotides, respectively, were
      detected. In 2 patients, the IAPP mRNA concentration of the tumour was lower than
      the insulin mRNA concentration; in the third patient, however, the specific IAPP
      hybridization signal was at least equal to that for insulin. Amyloid deposits
      were found in one solitary tumour and in the tumour from the MEN-I patient, both
      staining strongly positive with anti-IAPP antibodies; cytoplasmatic IAPP was
      weak. In conclusion, at least in some insulinomas, no constant relationship
      exists between insulin and IAPP expression.

PMID- 1362978
TI  - The presence of caring in nursing. Proceedings of the 13th International
      Conference on Human Caring. Rochester, New York, 1991.

PMID- 1362979
TI  - Spinal antinociceptive effects of [D-Ala2]deltorphin II, a novel and highly
      selective delta-opioid receptor agonist.
AB  - Pharmacological assays in isolated tissues and binding tests have recently shown
      that two peptides, with the sequence Tyr-D-Ala-Phe-Asp-(or Glu)- Val-Val-Gly-NH2,
      isolated from skin extracts of Phyllomedusa bicolor and named [D-Ala2]deltorphin
      I and II, respectively, possess a higher affinity and selectivity for delta
      opioid receptors than any other known natural compound. Since much evidence
      supports the role of spinal delta-opioid sites in producing antinociceptive
      effects, we investigated whether analgesia might be detected by direct spinal
      cord administration of [D-Ala2]deltorphin II (DADELT II) in the rat. The thermal
      antinociceptive effects of intrathecal DADELT II and dermorphin, a potent mu
      selective agonist, were compared at different postinjection times by means of the
      tail-flick test. The DADELT II produced a dose-related inhibition of the tail
      flick response, which lasted 10-60 min depending on the dose and appeared to be
      of shorter duration than the analgesia produced in rats after intrathecal
      injection of dermorphin (20-120 min). The analgesic effect of infused or injected
      DADELT II was completely abolished by naltrindole, the highly selective delta
      antagonist. These results confirm the involvement of delta receptors in spinal
      analgesic activity in the rat.

PMID- 1362980
TI  - Somatostatin as a mediator of the effect of neurotensin on pentagastrin
      stimulated acid secretion in rats.
AB  - Neurotensin and somatostatin have both been shown to inhibit gastric acid
      secretion, but no interaction between these peptides has been demonstrated. To
      determine whether somatostatin might be a mediator of neurotensin's effect on
      pentagastrin-stimulated gastric acid secretion, we performed the following three
      experiments. First, we collected 0.2-ml samples of portal venous blood as
      frequently as every 5 min, and we confirmed a significant release of somatostatin
      like immunoreactivity into portal venous blood during neurotensin-induced
      inhibition of acid secretion. This release of somatostatin-like immunoreactivity
      and inhibition of acid secretion were only seen in pentobarbital-anesthetized
      rats, but no sustained release of somatostatin-like immunoreactivity or
      inhibition of acid secretion occurred in urethane-anesthetized animals. In the
      second experiment, we analyzed portal plasma by high pressure liquid
      chromatography, and found that portal somatostatin-like immunoreactivity in blood
      collected during neurotensin infusion was composed of a single peak corresponding
      to somatostatin-14. In the third experiment, we found that infusion of antibody
      to somatostatin prevented neurotensin from inhibiting pentagastrin-stimulated
      acid secretion. Taken together, these data show that somatostatin, possibly from
      the stomach itself, is a necessary mediator of neurotensin's inhibitory effect in
      pentobarbital-anesthetized rats.

PMID- 1362981
TI  - Sex differences in the effects of Tyr-MIF-1 on morphine- and stress-induced
      analgesia.
AB  - There is evidence suggesting that the endogenous tetrapeptide, Tyr-MIF-1 (Tyr
      Prol-Leu-Gly-amide), has antagonistic or modulatory effects on opioid-mediated
      analgesia. There is also substantial evidence for sex differences in opioid
      effects, whereby male rodents display greater levels of opioid-mediated analgesia
      than females. In the present study, determinations were made of the effects of
      Tyr-MIF-1 on morphine- and restraint stress-induced opioid analgesia in adult
      male and female deer mice, Peromyscus maniculatus. Intraperitoneal treatment with
      Tyr-MIF-1 (0.10-10 mg/kg) reduced morphine- and stress-induced analgesia in both
      male and female mice, with Tyr-MIF-1 having markedly greater antagonistic effects
      in male than female mice. These results indicate that there are sex differences
      in the modulatory (antiopiate) effects of Tyr-MIF-1 on opioid-mediated analgesia.

PMID- 1362983
TI  - Prenatal exclusion of haemophilia A and carrier testing by direct detection of a
      disease lesion.
AB  - A novel mutation was detected in the Factor VIII gene of a sporadic case of
      severe haemophilia A. The lesion, a CGA-->TGA transition, converts Arg 795 to
      Term and adequately accounts for the severe phenotype observed. PCR/direct
      sequencing was used to confirm the carrier status in the mother. Exclusion of
      haemophilia A in an at-risk pregnancy was then achieved by demonstration of the
      absence of this lesion in fetal DNA from a chorionic villus sample. The mutation
      was also detectable by chemical cleavage of mismatch (CCM), which both confirmed
      the prenatal diagnosis and established the carrier status of the proband's
      sister. This example therefore serves to illustrate the potential of direct gene
      analysis in sporadic cases of haemophilia A and/or in families uninformative for
      known RFLPs.

PMID- 1362984
TI  - Prenatal diagnosis of metabolic diseases on chorionic villi obtained before the
      ninth week of pregnancy.
AB  - Nine pregnancies at risk for various metabolic disorders were monitored by
      prenatal diagnosis on chorionic villi obtained between the sixth and ninth weeks
      of pregnancy. A diagnosis of an affected fetus was made in five cases (Sandhoff,
      Tay-Sachs (2), Pompe's, GM1), while metachromatic leukodystrophy, GM1 (2), and
      Pompe's were excluded in four cases. It is concluded that chorionic villi are a
      reliable tissue for prenatal diagnosis of metabolic disorders also when obtained
      before the ninth week.

PMID- 1362985
TI  - Potential co-existence of haemophilia A and B carrier status in two sisters.

PMID- 1362986
TI  - [Spondylodiscitis caused by Bacteroides melaninogenicus].

PMID- 1362982
TI  - Recent advances in asthma.

PMID- 1362987
TI  - Growth of axons through a lesion in the intact CNS of fetal rat maintained in
      long-term culture.
AB  - The ability of neurons in the central nervous system (CNS) to grow through a
      lesion and restore conduction has been analysed in developing spinal cord in
      vitro. The preparation consists of the entire CNS of embryonic rat, isolated and
      maintained in culture. Conduction of electrical activity and normal morphological
      appearance (light microscopical and electron microscopical) were maintained in
      the spinal cord of such preparations for up to 7 d in culture. A complete
      transverse crush of the spinal cord abolished all conduction for 2 d. After 3-5
      d, clear recovery had occurred: electrical conduction across the crush was
      comparable with that in uninjured preparations. Furthermore, the spinal cord had
      largely regained its gross normal appearance at the crush site. Axons stained in
      vivo by carbocyanine dyes had, by 5 d, grown in profusion through the lesion and
      several millimetres beyond it. These experiments, like those made in neonatal
      opossum (Treherne et al. 1992) demonstrate that central neurons of immature
      mammals, unlike those in adults, can respond to injury by rapid and extensive
      outgrowth of nerve fibres in the absence of peripheral nerve bridges or
      antibodies that neutralize inhibitory factors. However, unlike the opossum, in
      which outgrowth occurred at 24 degrees C, although there was prolonged survival
      of rat spinal cords at this temperature, outgrowth of axons across the lesion
      required a temperature of 29 degrees C. With rapid and reliable regeneration in
      vitro it becomes practicable to assay the effects of molecules that promote or
      inhibit restoration of functional connections.

PMID- 1362988
TI  - K(+)-channel blockers restore synaptic plasticity in the neuromuscular junction
      of dunce, a Drosophila learning and memory mutant.
AB  - The effects of K(+)-channel blockers on synaptic transmission in dunce (dnc), a
      Drosophila learning and memory mutant, were investigated. Larvae dnc mutants lack
      facilitation and post-tetanic potentiation (PTP) at their motor end-plates; dnc
      mutants are also deficient in a form of phosphodiesterase, and exhibit abnormally
      high levels of cyclic adenosine 3',5'-monophosphate (cAMP). A two-microelectrode
      voltage-clamp was used to record end-plate currents and spontaneous end-plate
      currents from longitudinal ventrolateral third-instar larval muscle. The K(+)
      channel blockers 3,4-diaminopyridine (3,4-DAP) and tetraethylammonium (TEA), at
      micromolar concentrations, caused a reversible decrease in end-plate current
      amplitudes both in wild-type and mutant end-plates. In the presence of blockers,
      a period of high-frequency stimulation (tetanus) of the nerve gave way to a
      transient increase in the end-plate currents of dnc mutants resembling
      facilitation and PTP in normal end-plates; 3,4-DAP and TEA also restored
      facilitation and PTP in normal end-plates after incubation with a non
      hydrolysable analogue of cAMP (8Br-cAMP). It is suggested that a specific K+
      conductance might be relevant to the lack of synaptic plasticity at the dnc
      neuromuscular synapses.

PMID- 1362989
TI  - A kin selection model for the evolution of virulence.
AB  - The costs and benefits of parasite virulence are analysed in an evolutionarily
      stable strategy (ESS) model. Increased host mortality caused by disease
      (virulence) reduces a parasite's fitness by damaging its food supply. The fitness
      costs of high virulence may be offset by the benefits of increased transmission
      or ability to withstand the host's defences. It has been suggested that multiple
      infections lead to higher virulence because of competition among parasite strains
      within a host. A quantitative prediction is given for the ESS virulence rate as a
      function of the coefficient of relatedness among co-infecting strains. The
      prediction depends on the quantitative relation between the costs of virulence
      and the benefits of transmission or avoidance of host defences. The particular
      mechanisms by which parasites can increase their transmission or avoid host
      defences also have a key role in the evolution of virulence when there are
      multiple infections.

PMID- 1362990
TI  - Nonlinear mechanical responses of mouse cochlear hair bundles.
AB  - The stiffness of sensory hair bundles of both inner (IHC) and outer (OHC) hair
      cells was measured with calibrated silica fibres in mouse cochlear cultures to
      test the hypothesis that the mechanical properties of the hair bundle reflect
      processes underlying mechanotransduction. For OHCs, the displacement of the hair
      bundle relaxed with time constants of 6 ms for displacements which open
      transducer channels and 4 ms for displacements which close the channels. The
      corresponding values of the time constants for IHCs were 10 ms and 8 ms,
      respectively. A displacement-dependent change in the stiffness of the hair bundle
      was not observed when the bundle was displaced orthogonally to the direction of
      excitation. The stiffness of the hair bundle as a function of nanometre
      displacements from the resting position was remarkably nonlinear. The stiffness
      declined to a minimum from the resting stiffness by about 12% for OHCs and 20%
      for IHCs when the hair bundle was displaced by about 20 nm in the excitatory
      direction, and it increased by a similar amount when the bundle was displaced by
      20 nm in the inhibitory direction. The displacement at which the stiffness
      reached a minimum was within the most sensitive region of the hair-cell
      transducer function (receptor potential as a function of hair-bundle
      displacement), and the displacement at which the stiffness reached a maximum was
      at the point of saturation of the transducer function in the inhibitory
      direction. The nonlinear displacement-dependent compliance change is reversibly
      abolished, and the time constant of relaxation of the bundle for excitatory
      displacements is reversibly reduced, when mechanotransduction is blocked by the
      addition of either neomycin sulphate or cobalt chloride to the solution bathing
      the hair cells. The displacement-dependent compliance change was not apparently
      reduced when the receptor potential was attenuated through the substitution of
      sodium in the bathing solution with a less permeant cation, tetraethylammonium.
      These findings suggest that the nonlinear mechanical properties of the hair
      bundle are associated with aspects of the hair-cell mechanotransducer process.
      The mechanical properties of the hair bundle are discussed in relation to the
      'gating-spring' hypothesis of hair-cell transduction.

PMID- 1362991
TI  - Kinetics of intracellular calcium release by inositol 1,4,5-trisphosphate and
      extracellular ATP in porcine cultured aortic endothelial cells.
AB  - Quantitative, time-resolved measurements have been made of intracellular Ca ion
      release by inositol 1,4,5-trisphosphate (InsP3) and extracellular ATP in porcine
      aortic endothelial cells in tissue culture. Intracellular free [Ca] was detected
      with the calcium dye fluo-3 and InsP3 released intracellularly by photolysis of
      'caged' InsP3 in whole-cell voltage-clamped aortic endothelial cells. A rise of
      [Ca] was recorded at InsP3 concentrations greater than 0.2 microM. The timecourse
      at low InsP3 concentrations comprised a delay of mean 300 ms (range 266-330 ms),
      a peak in 2-3 s before declining with a half-time of 5-10 s. The delay and time
      to-peak decreased with increasing concentrations of InsP3 over the range 0.2-5
      microM. At very high concentrations of InsP3 (> 5 microM), the delay in the Ca
      response was short, always less than 20 ms. The results are consistent with a
      direct binding and gating action of InsP3 on the Ca channel of the cellular
      store. Following InsP3 action there is a refractoriness of the InsP3 Ca release
      process which recovers with a timecourse of half-time about 30 s. A comparison
      can be made between the timecourse of InsP3 and extracellular ATP actions. High
      concentrations of ATP (500 microM) acted with a delay of mean 1.8 s (range 1.2
      2.5 s), whereas even moderate concentrations of InsP3 acted much more quickly,
      suggesting that there are slow coupling steps before or during the production of
      InsP3 in response to extracellular ATP. Both ATP and InsP3 evoked an increase in
      membrane conductance to K+, probably via Ca.

PMID- 1362992
TI  - Detection and processing of vertical disparity by the human observer.
AB  - Based on the distinction between uniocular vertical magnification and vertical
      disparity, the induced size effect experiments were reinterpreted and new
      experiments done to show that vertical disparity signals can produce other
      stereoptic depth effects. The direction and efficiency of utilization of vertical
      disparity signals depend on the quadrant of the visual field and the stimulus
      position within it.

PMID- 1362993
TI  - Modelling the immune response to malaria with ecological concepts: short-term
      behaviour against long-term equilibrium.
AB  - A model for the human immune response to the malaria parasite Plasmodium
      falciparum is used to analyse the dynamics of an infection within an individual
      patient. Previous models either looked at competition between two parasite
      genotypes or at one parasite clone and the immune response to it. This model
      describes the course of an infection caused by the blood stages of two parasite
      genotypes differing in reproductive rate and in the immune response they elicit.
      The interactions between the genotypes can be interpreted as exploitative
      competition for red blood cells. Interactions between omnipotent immune cells and
      parasites resemble a predator-prey relation. In analysing these kinds of models,
      classical theoretical ecology usually deals with long-term behaviours, i.e. looks
      for equilibria and conditions for coexistence. However, especially in endemic
      regions with ongoing transmission, an equilibrium state of infections is
      unlikely. When reinfections with another parasite genotype were considered, the
      short-term dynamics of the infection changed dramatically, depending on which
      genotype was first, when the second one appeared, and what kind of immune
      response was elicited. If the slow development of immunity to malaria really is
      due to its genotype specificity, the effects of superinfections will be of great
      importance.

PMID- 1362995
TI  - The glial spike theory. I. On an active role of neuroglia in spreading depression
      and migraine.
AB  - The propagation mechanism of spreading depression (SD), which has been implicated
      in the pathophysiology of the neurological auras of migraine, remains enigmatic
      but is widely believed to depend primarily upon the behaviour of assemblies of
      neurons. It is proposed here, based upon a program of theoretical research, that
      the most essential constituent of SD is a slowly propagating, regenerative event
      in the neuroglial compartment. By altering the neuronal microenvironment, this
      glial spike helps trigger and coordinate the neuronal depolarization of SD; the
      glial spike is in turn facilitated by neuronally released agents acting at the
      neuroglial plasma membrane. The conduction velocity-determining propagation
      mechanism of SD is further proposed to be a wave of intracellular Ca(2+)-induced
      Ca2+ release (cytocal wave) that travels through the glial compartment of nervous
      tissue. Some implications for the improved understanding and clinical management
      of migraine are suggested. Excitability of glial cells of vertebrates has until
      now been demonstrated only in vitro, and its physiological significance has
      remained unknown. This work identifies a macroscopic reaction of neuronal tissue,
      known from the in vivo vertebrate brain for over 45 years, as a manifestation of
      neuroglial excitability.

PMID- 1362994
TI  - Statistical geometry of pancreatic islets.
AB  - Quantitative histomorphometric studies of the dynamics of growth and development
      of pancreatic islets in normal and pathological states pose substantial
      methodological and conceptual problems. We address these problems with the
      geometry of random fractals, and apply our methods to the analysis of islet
      regeneration in the alloxan-treated guinea-pig. In both experimental islet
      regenerated and control animals, islet centres are found to cluster in similar
      fractal subsets of dimension strictly less than 3, in agreement with the
      postulated origin of islets along a system of ductules, and suggesting that
      regeneration follows the same mathematical dynamics as original islet formation.

PMID- 1362996
TI  - A computational model of the analysis of some first-order and second-order motion
      patterns by simple and complex cells.
AB  - Although spatio-temporal gradient schemes are widely used in the computation of
      image motion, algorithms are ill conditioned for particular classes of input.
      This paper addresses this problem. Motion is computed as the space-time direction
      in which the difference in image illuminance from the local mean is conserved.
      This method can reliably detect motion in first-order and some second-order
      motion stimuli. Components of the model can be identified with directionally
      asymmetric and directionally selective simple cells. A stage in which we compute
      spatial and temporal derivatives of the difference between image illuminance and
      the local mean illuminance using a truncated Taylor series gives rise to a phase
      invariant output reminiscent of the response of complex cells.

PMID- 1362997
TI  - Dopamine autoreceptor agonists in the treatment of schizophrenia and major
      depression.
AB  - Dopamine autoreceptor agonists reduce the firing rate, synthesis, and release of
      dopamine in dopaminergic neurons by means of a negative feedback mechanism via
      stimulation of autoreceptors. Moreover, dopamine autoreceptor agonists are able
      to stimulate supersensitive but not normosensitive postsynaptic receptors. For
      dopamine autoreceptor agonists, therapeutic effects by readjustment of excessive
      or deficient dopaminergic function have been postulated for positive and negative
      schizophrenic symptomatology as well as for subtypes of depressive disorders.
      Investigations on the therapeutic effects of autoreceptor-nonselective dopamine
      agonists in schizophrenia or depression have yielded inconsistent results. In
      order to reduce the excess of central dopaminergic activity postulated by the
      dopamine hypothesis of schizophrenia, dopamine autoreceptor agonists have been
      tested in open clinical trials in positive schizophrenic symptomatology. However,
      administration of selective dopamine autoreceptor agonists like talipexole or
      roxindole did not result in a significant improvement of positive psychotic
      symptoms. In negative schizophrenic symptomatology, a dopamine deficit rather
      than an excess has been hypothesized. Current evidence from pilot studies
      suggests that dopamine autoreceptor agonists like roxindole may produce a minor
      to moderate improvement of symptoms like affective flattening, depressed mood,
      alogia, and avolition, possibly by stimulation of supersensitive postsynaptic
      dopamine receptors. For certain subgroups of depression, a reduction of
      functional dopamine activity has been postulated. In an open pilot study in
      patients with a major depression, roxindole demonstrated antidepressive
      properties comparable to those of standard antidepressants, justifying further
      double-blind controlled trials against reference drugs.

PMID- 1362998
TI  - [Paroxysmal neurological manifestations disclosing panic attacks].
AB  - Thirty-seven patients presented with paroxysmal neurological manifestations
      attributed to anxiety attacks. The manifestations included loss of consciousness,
      focal sensorimotor deficits, diffuse dysesthaesiae, visual disorders and tremor.
      They lasted 10 to 45 minutes and occurred once per day to once per week. Organic
      pathology was dismissed on the basis of normal examinations and atypical course.
      In all patients questioning revealed symptoms that were those of acute anxiety.
      The fact that these attacks took place in suggestive (circumstances e.g. in
      crowds and car driving), and that they could be induced by challenge tests
      hyperpnoea, infusion of lactate) suggested that these disorders were consecutive
      to panic attacks.

PMID- 1362999
TI  - [Current treatment of systemic vasculitis].

PMID- 1363000
TI  - [Therapeutic maintenance and tolerance of sulfasalazine in rheumatoid
      polyarthritis. Retrospective study of 95 patients].
AB  - This retrospective study evaluated treatment with sulfasalazine (SAS) in a mean
      dosage of 2.1 g/day in 95 patients with rheumatoid arthritis (RA) who were
      followed-up for 3 months to 4 years. Mean disease duration was 7 years; 79
      patients had previously received at least one disease-modifying drug. Four per
      cent of patients were lost to follow-up. Mean duration of treatment was 15 months
      (3 weeks-50 months). Treatment continuation rates were 57% at one year, 40% at
      two years, and 26% at three years. Reasons for discontinuation of SAS included
      adverse effects (n = 24), inefficacy (n = 33), and death unrelated to SAS therapy
      (n = 2). In four patients, SAS was discontinued within three months of the first
      dose because of a severe adverse effect (diffuse erythematous rash, diffuse
      bullous rash, hepatitis with jaundice, agranulocytosis). SAS-induced biologic
      markers for lupus were seen in one patient. Furthermore, 12% of evaluable
      patients developed antinuclear antibodies during SAS therapy. The SAS treatment
      continuation rate was higher (p = 0.05) among patients under 40 years of age (n =
      18) than among older patients. This difference was due to a correlation between
      age and tolerance with less SAS-induced side effects in patients under 40 years
      of age (p = 0.03). The SAS treatment continuation rate was unrelated to the
      duration of rheumatoid arthritis or number of previous maintenance treatments.
      This study suggests that rheumatoid arthritis patients under 40 years of age
      exhibit better tolerance to SAS therapy.

PMID- 1363001
TI  - A novel model to assess developmental toxicity of dihaloalkanes in humans:
      bioactivation of 1,2-dibromoethane by the isozymes of human fetal liver
      glutathione S-transferase.
AB  - Glutathione S-transferase (GST) isozymes from human fetal liver (16-18 weeks
      gestation) were purified by affinity chromatography followed by ion-exchange high
      performance liquid chromatography (HPLC). The purified isozymes were used to
      investigate toxicity of 1,2-dibromoethane(EDB) in an in vitro model of rat
      embryos in culture as passive targets. At least five isozymes of GST were found
      in the human fetal liver. Two anionic forms [pI values 5.5 (P-2) and 4.5 (P-3)]
      and one basic form [pI value 8.7 (P-6)] were clearly separated. The presence of
      two near-neutral forms was also identified. All the isozymes of the human fetal
      liver GSTs tested metabolized EDB (specific activities were 2.1, 7.0, and 2.0
      mumol of GSH consumed/min/mg protein for P-2, P-3, and P-6 isozymes,
      respectively). Covalent binding of EDB to DNA and protein was 144% and 212%
      higher, respectively, with the P-3 anionic isozyme when compared to the P-6 basic
      isozyme of GST. No covalent binding to either protein or DNA was observed with
      the P-2 isozyme. EDB bioactivation by the GST isozyme P-3 (15 units; 1 unit = 1
      nmol of GSH consumed/min) resulted in toxicity to cultured rat embryos.
      Significant reductions of crown rump length, yolk sac diameter, and the composite
      score of morphological parameters (Brown and Fabro method) were observed. The
      central nervous system, optic and olfactory systems, and the hind limb were most
      significantly affected. The results of this investigation suggest that EDB may be
      classified as a suspected developmental toxicant in humans.

PMID- 1363002
TI  - Teratogenic effects of N-nitrosodiethylamine in embryos of the hermaphroditic
      fish Rivulus marmoratus.
AB  - Exposure of N-nitrosodiethylamine (NDEA) to hermaphroditic fish (Rivulus
      marmoratus) embryos induced specific congenital malformations when the chemical
      was applied to embryos on days 0-6 post morula stage. This sensitive period
      generally coincided with the known period of organogenesis in this species, and
      the incidence of anomalies was clearly dose related. These results indicate that
      NDEA is teratogenic to fish embryos.

PMID- 1363003
TI  - N-alkyl-N-nitrosourea induced secondary structural changes in DNA from rat
      embryos and fetal brains in vivo.
AB  - N-methyl-N-nitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU) are gestational
      stage dependent teratogens and transplacental carcinogens capable of inducing
      neurogenic tumours in rats. Intravenous treatment of gravid Wistar rats showed
      that MNU is teratogenic but ENU is a transplacental carcinogen and may be a
      teratogen when administered on day 12 of gestation. Twenty-four hours after
      single doses of 2, 5, or 10 mg MNU/kg on day 12, dose dependent decreases in
      embryonic wet weight and total embryonic DNA were observed. Rats similarly
      treated with 2 and 5 mg MNU/kg showed dose dependent decreases in fetal brain DNA
      synthesis, DNA content, and wet weight 9 days later. Administration of single ENU
      doses of 1.5, 3, 6, 12, 48, and 80 mg/kg to day 12 embryos resulted in a dose
      dependent reduction in [methyl-14C]-thymidine (14C-TdR) incorporation into DNA
      after 24 h although total DNA amounts and embryonic wet weights were unaffected.
      Benzoylated DEAE-cellulose (BD-cellulose) chromatography fractionates DNA on the
      basis of secondary structure by stepwise elution of double-stranded DNA with 1.0
      M NaCl solution (SE-DNA) followed by elution of DNA containing single-stranded
      regions with caffeine solution (CE-DNA). Day 13 embryonic and day 21 fetal brain
      DNA was monitored by in vivo labelling with [methyl-3H]-thymidine on days 6 and 7
      of gestation. Significant reduction in percentages of CE-DNA (%CE-DNA) 24 h after
      treatment of day 12 embryos with 2, 5, or 10 mg MNU/kg were attributed to the
      necrotic effect of MNU. Day 12 treatment with MNU produced no change in %CE-DNA
      values of day 21 fetal brains. A teratogenic dose of 80 mg ENU/kg to day 12
      embryos resulted in significantly increased %CE-DNA values compared to controls
      but no changes were observed after 1.5 to 48 mg/kg. Analysis of the distribution
      of %CE-DNA values from the 80 mg ENU/kg treated litter showed that the increase
      in %CE-DNA was due to a second distinct population of embryos with higher %CE-DNA
      values than controls. Incorporation of 14C-TdR into embryonic and fetal brain DNA
      demonstrated the effects of treatment with these compounds on DNA synthesis in
      vivo. The relative %CE-DNA is expressed as the ratio of the percentage of
      caffeine-eluted 14C-labelled DNA to %CE-DNA (i.e., %CE-14C-DNA:%CE-3H-DNA). In
      the majority of control embryos the 14C-specific activity of CE-DNA was higher
      than the 14C-specific activity of SE-DNA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1363004
TI  - Further in vitro and in vivo mutagenicity assays with thiram and ziram
      fungicides: bacterial reversion assays and mouse micronucleus test.
AB  - The fungicides thiram and ziram have been assayed in a battery of nine bacterial
      strains of different genetic specificity. The results obtained suggest the
      induction of excisable DNA lesion(s), and indicate similar mutability of strains
      with AT or GC base pairs at target sites. This mutagenic profile is clearly
      distinct from that of oxidative mutagens, and it does not support the proposed
      role of oxidative stress in the mechanism of dithiocarbamates mutagenicity in
      bacteria. Furthermore, the bone marrow micronucleus test has been carried out in
      B6C3F1 mice with intraperitoneal administration of high grade thiram (12.5-50
      mg/kg) and ziram samples (2.5-10 mg/kg in males, and 5-20 mg/kg in females).
      Thiram produced a significant increase of micronucleated PCEs in male mice
      sampled 48 h after treatment with 25, 37.5, and 50 mg/kg. No significant increase
      was detected in treated females. Ziram, tested in a lower range of doses because
      of its higher toxicity, resulted negative in both sexes. Both the acute toxicity
      and the ratio polychromatic/normochromatic erythrocytes indicated some sex
      specificity in the toxic effects induced by these dithiocarbamates in the B6C3F1
      mouse.

PMID- 1363005
TI  - Reversible sensorimotor impairment following prolonged ventilation with
      isoflurane and vecuronium for acute severe asthma.
AB  - A patient with acute asthma developed severe sensorimotor neuropathy while being
      ventilated with isoflurane and receiving vecuronium and fentanyl. The neuropathy
      resolved spontaneously within three months of the episode. This unusual
      complication may result from prolonged use of inhalational anaesthesia or of
      vecuronium, or both.

PMID- 1363006
TI  - Feline Immunodeficiency Virus. Proceedings of an international conference. Davis,
      California, 4-7 September 1991.

PMID- 1363007
TI  - Effect of primary phase feline immunodeficiency virus infection on cats with
      chronic toxoplasmosis.
AB  - The effect of primary phase feline immunodeficiency virus (FIV) infection on
      clinical signs, hematological values, Toxoplasma gondii oocyst shedding, T.
      gondii-specific serology, T. gondii-specific cell-mediated immune responses, non
      specific cell-mediated immune responses, and lymphocyte subpopulations from cats
      with experimentally induced chronic toxoplasmosis was studied. No significant
      clinical or hematologic abnormalities were noted following inoculation with FIV.
      T. gondii-specific IgM was significantly increased, concanavalin A, T. gondii
      tachyzoite antigen and T. gondii secretory antigen induction of lymphocyte
      transformation were significantly suppressed, and CD4+ cell numbers were
      significantly decreased following inoculation with FIV. The changes were
      attributed to FIV effects on the immune system and resultant activated
      toxoplasmosis.

PMID- 1363008
TI  - Use of two virustatica (AZT, PMEA) in the treatment of FIV and of FeLV
      seropositive cats with clinical symptoms.
AB  - In the present study the therapeutic efficacy and the side effects of two
      antiretroviral compounds used in human acquired immunodeficiency syndrome (AIDS)
      research, 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine, Retrovir) and 9-(2
      phosphonylmethoxyethyl)adenine (PMEA), were investigated in the treatment of cats
      naturally infected with feline immunodeficiency virus (FIV) and cats naturally
      infected with feline leukemia virus (FeLV). AZT was administered subcutaneously
      at a dose of 5 mg kg-1 body weight every 12 h and PMEA was administered
      subcutaneously at a dose of 2.5 mg kg-1 body weight every 12 h during a 3 week
      hospitalization. The therapeutic efficacy of both compounds was investigated.
      There was a stronger potency of PMEA than of AZT on the regression of stomatitis
      in FIV and in FeLV infected cats. In addition, in FIV infection PMEA had a
      stronger effect on the improvement of the general clinical status. Both
      antiretroviral compounds were potent agents to improve the immunologic status of
      FIV infected cats by raising the CD4/CD8 ratio. In FeLV infection PMEA and AZT
      appeared to reduce antigenemia. The hematological side effects caused by PMEA
      were severe and stronger than those of AZT. Therefore the advantage of PMEA in
      clinical and immunologic improvement was diminished by the hematologic disorders,
      which do not allow long term treatment with this drug in the dose used.

PMID- 1363009
TI  - Immunization-induced decrease of the CD4+:CD8+ ratio in cats experimentally
      infected with feline immunodeficiency virus.
AB  - In a previous experiment a group of 15 specified pathogen free (SPF) cats were
      experimentally infected with a Swiss isolate of feline immunodeficiency virus
      (FIV). A group of 15 SPF cats served as FIV negative controls. Nine cats of each
      group were vaccinated with a recombinant feline leukemia virus (FeLV) vaccine,
      six cats in each group with a placebo vaccine. All vaccinated cats developed high
      antibody titers to FeLV and were protected against subsequent FeLV challenge
      infection. In both control groups five of six cats became persistently infected
      with FeLV. Unexpectedly, the primary immune response to the vaccine antigen was
      significantly higher in the FIV positive group than in the FIV negative. The
      secondary response was stronger in the FIV negative cats. The goal of the present
      investigation was to further study the immune response in these 30 cats. They
      were immunized twice with the synthetic peptide L-tyrosine-L-glutamic acid
      poly(DL-alanine)-poly(L-lysine) (TGAL) 21 days apart. Blood samples were
      collected on four occasions during the immunization process. They were tested for
      antibodies to TGAL, complete blood cell counts and CD4+, CD8+ and pan-T
      lymphocyte counts. The following observations were made: (1) in contrast to the
      FeLV vaccine experiment, the primary immune response to TGAL was not
      significantly stronger in the FIV positive cats when tested by enzyme-linked
      immunosorbent assay (2). The absolute size of the CD4+ lymphocyte population was
      distinctly smaller in the FIV positive than in the FIV negative cats. The lowest
      CD4+ values were found in the dually FIV/FeLV infected cats. (3) A population of
      CD8+ lymphocytes was identified that was characterized by a distinctly weaker
      fluorescence. The size of this population increased in FIV positive and decreased
      in FIV negative cats during the TGAL immunization experiment. (4) The CD4+:CD8+
      ratio increased in FIV negative cats during TGAL immunization from 1.9 to 2.3. In
      contrast, in FIV positive animals the CD4+:CD8+ ratio decreased significantly
      from 1.9 to 1.3 during the same period. From these and earlier data it was
      concluded that in short-term FIV infection the immune response to T-cell
      dependent antigens may be increased over that of the controls. Immune suppression
      develops gradually with duration of the infection. The significant drop of the
      CD4+:CD8+ ratio over a 5 week immunization period suggests that antigenic
      stimulation may accelerate the development of immune suppression in FIV positive
      cats. If this is a general feature, FIV infection may provide a particularly
      interesting model for studying the pathogenesis of AIDS.

PMID- 1363010
TI  - Persistent upregulation of MHC class II antigen expression on T-lymphocytes from
      cats experimentally infected with feline immunodeficiency virus.
AB  - A significant elevation in the percentage of CD4+ and CD8+ T-lymphocytes
      expressing major histocompatibility complex (MHC) Class II antigens was observed
      in the blood of cats shortly after they were experimentally infected with feline
      immunodeficiency virus (FIV). In addition to an increase in the relative
      proportion of T-lymphocytes expressing Class II antigens, there was an increase
      in the density of Class II antigens on the cell surface. These elevations were
      still evident at the completion of the 5 month study. A second group of cats that
      had been infected with FIV for almost 5 years, and with either normal or
      abnormally low levels of CD4+ T-lymphocytes, had similar elevations in MHC II
      expression, suggesting that such abnormalities are lifelong. Cats with chronic (2
      year) feline leukemia virus (FeLV) infection or dual FIV/FeLV infections also
      showed similar alterations in MHC II expression on CD4+ and CD8+ T-lymphocytes,
      suggesting that these alterations were not FIV specific. Feline T-lymphocytes
      expressed more MHC II antigen and interleukin-2 (IL-2) receptor following
      stimulation in vitro with conconavalin A and IL-2, demonstrating that feline T
      lymphocytes respond to activation signals in a manner similar to T-lymphocytes of
      other species. However, changes in MHC II expression on T-cells of FIV infected
      cats were not explainable by viral induced T-cell activation alone, because FIV
      infected cats with elevated MHC II expression did not have coincident elevations
      in IL-2 receptor expression.

PMID- 1363012
TI  - [Warning medical assistance and co-workers in the medical practice].

PMID- 1363011
TI  - Interaction of acute feline herpesvirus-1 and chronic feline immunodeficiency
      virus infections in experimentally infected specific pathogen free cats.
AB  - Cats with or without chronic feline immunodeficiency virus (FIV) infection were
      exposed to feline herpesvirus, type 1 (FHV-1). FIV infected cats became sicker
      than non-FIV infected cats and required more supportive treatment. However, there
      were no differences in the length of their illness or in the levels and duration
      of FHV-1 shedding. FHV-1 infection caused a transient neutrophilia at Day 7 with
      a rapid return to preinfection levels. The neutrophilia coincided with a
      transient lymphopenia that was accompanied by a decline in both CD4+ and CD8+ T
      lymphocytes. A brief decrease in the CD4+/CD8+ T-lymphocyte ratio occurred at Day
      14 in both FIV infected and non-infected cats. This decrease was mainly the
      result of an absolute and transient increase in CD8+ T-lymphocytes. CD4+ and CD8+
      T-lymphocyte numbers and CD4+/CD8+ T-lymphocyte ratios returned to baseline
      within 4-8 weeks in both FIV infected and non-infected cats. FIV infected cats
      produced less FHV-1 neutralizing antibodies during the first 3 weeks of infection
      than non-FIV infected animals. The IgM FHV-1 antibody response was depressed in
      FIV infected cats whereas the IgG antibody response was unaffected. FHV-1
      infection evoked a comparable transient loss of lymphocyte blastogenic responses
      to concanavalin A and pokeweed mitogen in both FIV infected and non-infected
      cats. However, response to pokeweed mitogen took longer to return to normal in
      FIV infected animals. Lymphocytes from FIV infected cats had a greater and more
      sustained proliferative response to FHV-1 antigen than non-FIV infected cats. The
      ongoing IgG antibody response to FIV was not affected by FHV-1 infection.

PMID- 1363013
TI  - [Reading, hearing, understanding].
AB  - The relationship between reading comprehension, listening comprehension, and two
      indicators of intelligence (verbal reasoning, speed of information processing) is
      analyzed on the basis of a hierarchical monistic model. Two tests (reading
      comprehension, listening comprehension) were administered to 221 4th graders in
      classroom context at two sessions. Order of administration was balanced.
      Additionally, verbal reasoning and speed of information processing were assessed,
      marks in German were collected. On the whole, performance in listening
      comprehension exceeds reading comprehension as expected for children at that age.
      In spite of this mean difference a high correlation between the variables was
      found. In accordance with theory, the relationship between reading and listening
      comprehension is stronger when the influence of reading specific abilities is
      lower and reading material is less complex. Listening comprehension appears to be
      of more relevance to the prediction of reading comprehension than verbal
      intelligence, speed of information processing, and marks in German, even when
      listening comprehension is introduced as the last predictor in multiple
      regression analysis. It is suggested to emphasize the role of listening
      comprehension in the assessment and prognosis of reading disabilities.

PMID- 1363014
TI  - Retrieval of action phrases: the efficacy of verb cues and noun cues.
AB  - Memory for noun cues has been shown to be superior to memory for verb cues. This
      study investigates two factors that might influence this noun-cue superiority
      effect: pre-experimental associations between the cue and the target, and
      encoding strategies. Subjects were to study a list of noun-verb phrases. The pre
      experimental associations between the two components of the phrases were either
      symmetric or asymmetric, and either strong or weak. One group of subjects studied
      the list under a standard learning instruction. The other group was required to
      enact the phrases. The results show that the noun-cue superiority is modulated by
      the variation of pre-experimental associations, that enacting considerably
      improves cued recall performances, and that enacting neither influences the
      effects of pre-experimental associations nor the efficacy of the two cuetypes.

PMID- 1363015
TI  - [Constraint and inclination for reducing complexity--social cognitive aspects of
      moral judgment in children].
AB  - When processing information about their reality human beings systematically
      reduce objective complexity. This is not only true in cognitive problem solving,
      but also in other every-day situations, e.g., when decisions in situations of
      moral relevance are required. From a developmental psychological point of view
      the adequate handling of such situations requires, on the one hand, an age
      related differentiation of social cognitions, and, on the other hand, an
      increasingly effective structuring and integration of information. The latter
      developmental process, however, bears the danger that an adequate psychosocial
      development is substituted by a tendency toward complexity reduction in the sense
      of oversimplification due to the fact that such a tendency may suggest situation
      specific alternative actions which are seemingly "easier to handle". In an
      empirical study with 176 students from Polytechnical High Schools in (East
      )Berlin the hypothesis is tested if a tendency toward oversimplification in
      (fictitious) situations of moral relevance is systematically related to deviant
      behavior at school. Results show that indeed deviant students have a stronger
      tendency toward oversimplifying social cognitions than non-deviant students.
      Furthermore, it can be shown that this result is not moderated by possible sex,
      age or academic performance effects. As results with regard to moral judgement in
      the Kohlbergian sense differ substantially in their relation to academic
      performance and to behavioral deviance, it is assumed that the two judgement
      processes differ conceptually.

PMID- 1363018
TI  - [Arthrodesis of the upper ankle joint. Indications, technique, results].
AB  - From 1984 to 1990 a total of 119 arthrodesis of the upper ankle joint were
      performed at the Hospital of Accident Surgery of the Trade Association in
      Frankfurt am Main. The results of 98 patients after an arthrodesis of the upper
      ankle joint are documented by an x-ray control series and patient files,
      including the expertise on the medical status of pensioners plus a follow-up
      examination of 34 patients. The indications and the results are discussed on the
      basis of the various procedures. The results confirm the method of a compressions
      arthrodesis with an extension screw in case of a posttraumatic arthrosis of the
      upper ankle joint, while a fixateur externe should be used in case of chronical
      osteomyelitis, osteoporotic bones, extensive tissue swellings and after a pilon
      or talus fragment fracture.

PMID- 1363017
TI  - [Pathomechanical aspects of intra-articular calcaneus fractures. Typing, grading
      and surgical therapy].
AB  - The forces to produce fractures of the os calcis are combined compression and
      shear under a cranio-caudal impulse of 10-40 kN and a short time of stroke about
      10-40 ms. The main patterns in biomechanics of calcaneal fractures are the time
      of stroke and the geometrical position of the foot in the moment of impact.
      Furthermore individual structural changes of the calcaneal cancellous bone, age,
      diseases as Diabetes mellitus and vascular obliterations are to be respected.
      Operative treatment of these fractures needs an understanding of the
      pathomechanism of the intracalcaneal shear-tension-forces. With plantarflexion of
      the foot combined with vertical forces within 40 ms to the anterior talocalcanear
      facette impact-fractures of the anterior part can be expected. These forces
      develop a posterior directed shear tension parallel to the axis of the os calcis,
      dividing the bone horizontally in two parts (Typ A, 44-56%), well-known as tongue
      type fracture. Compression of the posterior talo-calcaneal joint leads to an
      impact of this structure producing the joint depression type within about 30 ms
      in dorsoflexion of the foot (Type B, 42%) together with sagittal shear fractures.
      High-energy forces are supposed to produce the so-called primary fractures of the
      sustentacular process in about 10 ms in a supinated position of the foot (Type C,
      2-10%); these fractures represent in cases of dislocation an indication for open
      reduction and internal fixation. In our own experience with 45 cases in 35
      patients using the lateral or/and medial approach no infection happened. Palmer's
      lateral approach was preferred.

PMID- 1363016
TI  - Ultrastructural localization of Alzheimer amyloid beta/A4 protein precursor in
      the cytoplasm of neurons and senile plaque-associated astrocytes.
AB  - The ultrastructural localization of amyloid beta/A4 protein precursor (APP) in
      the brains of control and Alzheimer's disease patients was examined
      immunohistochemically using antisera against the N and C termini of APP. In both
      control and Alzheimer brains, immunoreaction for APP was seen in the cytoplasm of
      most neurons, on plasma membranes, outer membrane of mitochondria, granular
      substance and neurofilaments. Cell bodies and foot processes of astrocytes,
      containing glial filaments, were also labeled. In primitive and classic type
      senile plaques, APP immunoreaction products were localized in the astroglial
      processes that surrounded the amyloid mass of the senile plaques. Swollen
      degenerating neurites in the senile plaques were also labeled. Amyloid fibrils
      were negative with APP antisera.

PMID- 1363019
TI  - [The value of digital luminescence radiography within the scope of traumatologic
      follow-up examinations].
AB  - At the present time we cannot unhesitatingly recommend the general use of digital
      luminescence radiography in traumatological follow-up examinations. Marked
      drawbacks of this method are, for example, sudden changes in contrast in the
      marginal areas of osteosynthesis material, occasional limitations in the detailed
      assessment of spongious structures and problems in respect of imaging geometry.
      By modifying the image processing parameters, increasing the image matrix and
      enlarging the format spectrum, however, these problems should be capable of being
      resolved in the future. Positive features, on the other hand, are even now the
      possibility of reducing the dosage to a marked degree in many traumatological
      follow-up examinations, especially in children and adolescents, and in case of
      conservatively treated fractures. In the long run we can foresee the routine use
      of digitalised examination methods on traumatology coupled with the possibility
      of storage in an image filing and communication system, although this is at
      present not yet feasible due to lack of requisite experience and the cost of the
      necessary equipment.

PMID- 1363020
TI  - [An analysis of conservative therapy in 376 patients with paraplegia after
      injuries of the spine].
AB  - In 376 cases of paraplegia after lesions of the vertebral column which had been
      treated exclusively by conservative methods we were interested in changes of the
      neurological status, if any, during inpatient treatment, as well as in the rate
      of complications, the stability of the vertebral column and the immobilisation
      time and period of hospitalisation. 70.7% of the patients were primarily
      completely paralysed at admission to hospital; 6.4% of them displayed
      neurological improvement, compared to 49.5% of the primarily not fully paralysed
      patients. With decreasing height of the site of lesion of the vertebral column
      the rate of neurological improvement increased to a statistically significant
      extent. The neurological status did not deteriorate in any of the patients.
      Instabilities of the vertebral column were rare in our patient material,
      occurring in only 0.8% of the exclusively conservatively treated lesions of the
      thoracic and lumbar vertebral column. The average rate of complications was
      13.9%, the immobilisation time approx. 10.8 weeks and the hospitalisation period
      on the average 25.6 weeks.

PMID- 1363021
TI  - [Epidural "sulmycin implant" coverage for local prevention of infection in
      surgical management of open craniocerebral injuries].
AB  - In various series reported in the literature on the operative management of
      severe head injuries with compound depressed skull fractures and penetrating
      wounds of the brain, the rates of infection differ from 1 to 17%. In this paper
      the operative experience with 22 cases of penetrating head injuries is discussed.
      In conventional operative therapy, depressed skull fracture and lacerated dura
      were covered by "Sulmycin Implant" containing Gentamycin as a helpful
      bacteriological barrier. 18 patients survived, 7 patients had severe neurological
      defects, 5 patients had mild neurological deficits and 6 patients recovered
      completely. There were no signs of suppurative complications in superficial
      wounds or in the brain. 4 patients died due to their severe brain damage with
      multiple contusional lesions. Postoperative complications were as follows: one
      patient suffered extradural and one patient subdural rebleeding. Another patient
      with a frontal base skull fracture suffered a pneumatocele because the fracture
      was not correctly covered. The revision was done successfully using the "Sulmycin
      Implant". Presently, however, the intradural use of "Sulmycin Implant" is not
      recommended without further testing for the level of gentamycin in the
      cerebrospinal fluid which is released by the "Sulmycin Implant".

PMID- 1363023
TI  - [Legal aspects of the risk of surgical malpractice: infection of the surgical
      wound].

PMID- 1363022
TI  - [Benefits and risks of surgical therapy of acute lateral fibular ligament rupture
      of the upper ankle joint. Results of a retrospective study].
AB  - In 60 patients with an intra-operatively confirmed first-time tear of the lateral
      ligaments of the ankle joint an examination carried out after a period ranging
      from 11.6 and 35 months post-op. showed that ligament suturing coupled with
      immobilisation for 6 weeks was not associated with any major or persistent
      impairment. The important advantage of the procedure was the possibility of
      accurately determining the extent of the injury, together with the chance of
      providing suitable and immediate correction. In 91% of the patient group, a
      comparison of sides revealed equal or greater stability of the surgically treated
      ankle joint. Even when occasional temporary, varyingly pronounced, sensory
      disorders are taken into account, in comparison with the possibilities of
      conservative therapy, we consider that these results confirm a tear of the
      lateral ligaments of the ankle to be a justifiable indication for surgery.

PMID- 1363024
TI  - [Power stapling in trauma surgery. An improvement of trauma surgery technique?].
AB  - Power staple fixation of fracture fragments represent an enrichment of
      technological possibilities in adaptive osteosynthesis. We gained some experience
      with a variety of indications. The advantage of this method can be seen in the
      simple and fast way of application. Observing limited indications excellent
      results can be achieved.

PMID- 1363025
TI  - Proceedings of the 1st European Symposium on Production, Evaluation and
      Preservation of Stallion Semen. Uppsala, Sweden, October 1-2, 1992.

PMID- 1363026
TI  - Prevention and management of NSAID-induced ulcers.

PMID- 1363027
TI  - Prophylactic pharmacologic treatment of asthma.

PMID- 1363028
TI  - [Decrease of postoperative morbidity in coronary surgery using the two internal
      mammary arteries].
AB  - The surgical risk of bilateral internal mammary artery grafting was analyzed in
      100 successive patients separated chronologically into two groups. These groups
      were not statistically different in terms of age, severity of angina, and extent
      of coronary artery disease. The number of grafts per patient and the time of
      aortic cross clamping were not statistically different in the two groups. The
      postoperative mortality was 1% in the 100 patients. The incidence of
      perioperative myocardial infarction was not statistically different in the two
      groups. No mediastinal suppuration was observed. The mean postoperative
      hemorrhage was 633 +/- 558 ml in the first 50 patients and 560 +/- 410 ml for the
      last 50 patients (p < 0.05). The percentage of patients receiving no homologous
      blood transfusion was 64% in the first 50 patients and 94% in the last 50
      patients. The percentage of phrenic palsy was 36% in the first 50 patients and 6%
      in the last 50 patients (p < 0.05). With surgical experience, the risk of
      coronary bypass with bilateral internal mammary artery was lowered and very
      similar to the surgical risk of conventional aorto-coronary bypass with saphenous
      veins or one mammary artery.

PMID- 1363029
TI  - [Place of the right gastro-epiploic artery in coronary revascularization by
      exclusive arterial grafts].
AB  - From March 1990 to July 1991, 35 patients underwent coronary artery bypass grafts
      using the right gastro-epiploic artery (GEA). Twenty-nine patients had
      exclusively arterial grafts using a combination of GEA and internal mammary
      artery (IMA) in situ. The selection criteria for this group of 29 patients
      included a life expectancy exceeding ten years to avoid the need for reoperation
      due to deterioration of the grafts. This group consisted of 27 men and two women
      under the age of 70 years (mean age: 58 years, range: 36 to 70), 11 patients
      (38%) were under the age of 50 years and 15 (52%) were under the age of 60 years.
      Cardiac status was relatively well preserved. The mean ejection fraction was 58%
      (range: 25-70%). Fourteen patients (48%) had had a preoperative myocardial
      infarction. Fifty-five p. cent were smokers, 41% suffered from HT and 31% had a
      dyslipidaemia. Six patients (20%) had respiratory failure, 6 others (20%) were
      severely overweight and 2 patients were diabetic. According to the NYHA
      classification, 14 patients (48%) were stage IV, 9 patients (31%) were stage III
      and 6 patients (20%) were stage II. The mean number of bypass grafts per patient
      was 2.8 and 8 sequential bypass grafts (27%) were performed. The GEA was used in
      29 cases, the left IMA was used in 28 cases, the right IMA was used in 13 cases
      and the epigastric artery was used as a free graft in 3 cases. Associated lesions
      included a resected left ventricular aneurysm. No associated valve procedures
      were performed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363030
TI  - [Use of the internal mammary artery as a free graft with reimplantation of the
      proximal end onto the ascending aorta. Apropos of 39 cases].
AB  - From January 1987 to January 1991, 104 patients received bilateral internal
      mammary artery grafts and 39 of them had coronary bypass with a free graft
      implanted on the ascending aorta. There were 35 men, with a mean age of 57.35
      years (range 41 to 70 years). 87% of them had stable angina, and 23 had
      preoperative myocardial infarction. The left ventricular function was good in 77
      per cent of cases. 23 patients had three vessel disease (61.5%), 13 two vessel
      diseases (30.7%), 2 one vessel disease (5.12%) and one a left main coronary
      stenosis. Left internal mammary artery was used in two patients on the left
      descending artery and the right internal mammary artery was used in 37 patients:
      15 on the circumflex, 15 on the right coronary, 4 on the LDA and 3 on the
      diagonal artery. Five patients had one graft, 32 two grafts and one three grafts
      (bilateral mammary and saphenous vein). Hospital mortality was 2.56% (1 patient)
      and there were 2 late deaths (5.12%). There were 5 perioperative myocardial
      infractions (12.8%) and no sternal infections. The mean follow up is 21 months
      (range 3 to 46 months). At follow-up, 34 patients (87.2%) were asymptomatic, and
      there were no myocardial infarctions. Postoperative angiography in 8 patients
      (mean postoperative time 2.5 months) showed that all the grafts were patent. This
      analysis demonstrates that free IMA graft has a low operative risk and provides
      excellent long term functional improvement and survival.

PMID- 1363032
TI  - [Beta-blockaders and atheroma regression: a necessary evaluation?].
AB  - Beta-blockers have been shown to have a beneficial effect especially regarding
      secondary prevention in coronary patients. The reduction in global mortality is
      most noticeable with respect to sudden death, which suggests an antiarrhythmic
      effect, but other non-lethal ischaemic events are also less frequent. The
      explanation of this observation is certainly multifactorial: some results point
      to a potential action on the development of atherosclerotic lesions. This
      justifies experimental and clinical studies of this hypothesis with this
      pharmacological group of drugs.

PMID- 1363031
TI  - Antinociceptive action of dopamine agonists in the nucleus raphe magnus of rats
      is mediated by D2 receptors.
AB  - We have shown previously that the dopamine agonist apomorphine is antinociceptive
      when injected into the nucleus raphe magnus of rats, presumably via stimulation
      of descending antinociceptive pathways. We have now extended the investigation to
      receptor-specific agonists. We measured nociception in conscious Sprague-Dawley
      rats, using the latency of the first flexor response following tail immersion in
      water at 49 degrees C, before and after injection of agonists into the nucleus
      raphe magnus through chronically implanted cannulae. The D2 agonist PPHT HCl
      produced an increase in latency, i.e. hypoalgesia, for 30 min after injection of
      doses of 10 and 20 nmol. The lowest dose of the D1 agonist SKF 38393 produced no
      change in latency, but a bimodal response was found at the higher two doses (20
      and 200 nmol), with hypoalgesia at 15 min, followed by a sustained hyperalgesia.
      The dopamine autoreceptor agonist R (+)-3PPP produced a significant hypoalgesia
      at 10 and 20 nmol 15 min after injection, with no subsequent hyperalgesia. Our
      results are consistent with the hypothesis that the antinociceptive action of
      dopamine in the rat nucleus raphe magnus is mediated by the D2 receptor.

PMID- 1363033
TI  - [Methodological problems in evaluating lipid lowering drugs. Vth workshop on
      clinical pharmacology and therapeutics. Bandol, 3-4 May 1991].

PMID- 1363034
TI  - Dosimetry workshop: extremely-low-frequency electric and magnetic fields. Carmel,
      California, March 20-22, 1991.

PMID- 1363035
TI  - [Communication between stem cells and the hematopoietic microenvironment.
      Experimental data and models of interaction].
AB  - The aim of this review is to analyze the different ways by which stem cells and
      microenvironmental cells may interact. Stem cells are defined as immature cells
      that ensure the continuous renewal of blood cells. This small set of marrow cells
      comprises different kinds of cells, differing by their degree of maturity, their
      commitment, self-renewal ability and repopulating capacity. Microenvironmental
      cells are fixed marrow cells involved in stem cell survival, proliferation and
      differentiation. In vivo studies on the distribution within spleen or marrow, of
      stem cells injected to lethally irradiated mice, have suggested that cells of the
      microenvironment play a significant role in stem cell proliferation and
      differentiation. This role has been demonstrated using an in vitro model, i.e.
      the long-term marrow cultures as described in 1976 by M. Dexter. Analysis of stem
      cell maintenance in this culture system has made it possible to define the
      different means by which stromal cells and macrophages (the microenvironmental
      cells) may control stem cell behavior. Different molecules play a critical role:
      cytokines (growth factors and inhibitors), adhesion molecules (cell adhesion
      molecules and molecules belonging to the extracellular matrix) and eventually
      small peptides. It appears nowadays possible to materially represent the
      hemopoietic niche, whose existence was postulated by R. Schofield 10 years ago
      for theoretical reasons related to the the physiology of stem cells.

PMID- 1363036
TI  - [Long-term tolerability of formoterol in chronic obstructive bronchopathies].
AB  - Formoterol aerosol, a long-acting new beta 2-mimetic was administered over a year
      at a dose of 12 micrograms twice daily, to 62 chronic obstructive bronchitics of
      mean age 66 +/- 6 years and of whom the basal VEMS was at 12,801 +/- 0.59.
      Clinical tolerance of the product was good with undesirable effects in 13
      patients, the most frequent being shaking. No untoward effect was seen on
      systolic or diastolic arterial pressure, or the heart rate over successive visits
      at 1, 3, 6, 9 months and one year. Electrocardiographic surveillance found in
      only four patients electrical abnormalities that may be due to Formoterol, these
      were patients without previous cardiac problems but of advanced mean age.
      Functionally, a significant improvement of basal VEMS was noticed from the 6th
      month. The VEMS improved significantly after administration of 12 micrograms on
      successive visits, without tachyphylactic signs. Well tolerated, with functional
      benefits, Formoterol is a promising product amongst the long-acting beta 2
      mimetics. Its usefulness and limitations in the basic treatment of these chronic
      bronchopathies remains to be defined.

PMID- 1363037
TI  - Polymorphism of the Pa gene.
AB  - PROBLEM: This study was undertaken to identify the number of alleles of the Pa
      gene at the DNA level and to correlate the presence of the different alleles with
      the ability of a strain to elicit an anti-Pa antibody response when mated with a
      WF female. The Pa gene is present in both Pa+ and Pa- strains of rats, but it has
      unique restriction fragment length polymorphisms (RFLP) in the two types of
      strains: 1.7 kb in Pa- and 1.8 kb in Pa+XbaI digests using a probe derived from
      the Pa gene. RESULTS: Examination of DNA from a variety of strains using
      different enzymes showed that there were characteristic RFLP patterns for Pa+ and
      Pa- strains. Strains of the b haplotype, however, had an intermediate RFLP
      pattern, and all of these strains had a relatively low level of reactivity with
      anti-Pa antibody. CONCLUSIONS: Thus, there are three alleles of the Pa gene based
      on their level of expression: Paa, high; Pab, low; and Pa-, none.

PMID- 1363038
TI  - Increased epileptogenesis in the immature brain.

PMID- 1363040
TI  - GABA and glutamate neurotransmission in the C57BL/10 sps/sps mouse: a mutant with
      absence-like behavior.

PMID- 1363039
TI  - Inhibitory and excitatory amino acid receptors, c-fos expression, and calcium
      binding proteins in the brain of baboons (Papio hamadryas) that exhibit
      'spontaneous' grand mal epilepsy.

PMID- 1363041
TI  - Neurochemical remodelling of the hippocampus in human temporal lobe epilepsy.

PMID- 1363042
TI  - Neurochemical changes in the hippocampus of rats with spontaneous recurrent
      seizures.

PMID- 1363043
TI  - Intrahippocampal tetanus toxin produces generalized convulsions and
      neurodegeneration in rats: antagonism by NMDA receptor blockers.

PMID- 1363044
TI  - Biochemical and functional studies on noradrenergic and peptidergic
      neurotransmission in hippocampal kindling.

PMID- 1363045
TI  - Age-dependent changes in excitability of rat neocortical neurons studied in
      vitro.

PMID- 1363046
TI  - Prognostic significance of proliferating cell nuclear antigen-positive growth
      fraction in gastric adenomas.
AB  - The proliferative activity of gastric adenomas from 18 patients (42 endoscopic
      procedures) was compared with follow-up results. These cases were gastric
      adenomas proven by follow-up with repeated endoscopic procedures for more than 2
      years, or were confirmed as gastric adenocarcinoma thereafter by histopathologic
      examination. Among the eighteen cases, nine showed carcinoma in the subsequent
      biopsies (group 1) and the remaining nine did not result in carcinoma (group 2).
      The proliferating cell nuclear antigen (PCNA) positivity rates of the two groups
      were significantly different (P < 0.01). The average PCNA positivity in group 1
      was 33.1%, while it was 10.0% in group 2. The risk of developing carcinoma
      increased as the PCNA positivity increased: 0% in the low PCNA positivity group,
      41% in the mid-positivity group and 89% in the high positivity group. We
      concluded that growth fraction could be taken into account as one of the most
      important prognostic factors for gastric adenoma, and accordingly repeated
      endoscopic biopsies with close follow-up should be carried out especially in the
      high PCNA positivity group.

PMID- 1363047
TI  - Compartmentalization of monoaminergic synaptic vesicles in the storage and
      release of neurotransmitter.
AB  - Monoaminergic nerves are characterized by the presence of a population of small
      synaptic vesicles (40-60 nm in diameter) containing a few large vesicles (80-90
      nm in diameter). Thus, although both types of vesicles contain monoamines, the
      small vesicles must be considered as the organoid responsible for the storage and
      release of the neurotransmitter, whereas the large ones possibly are involved in
      the modulation of the process. The small vesicles are electron-lucent or have an
      osmiophilic electron-dense core that is always linked to the vesicle membrane.
      Considering morphological and histochemical evidence under different experimental
      conditions, we proposed the existence of two compartments in the small vesicles:
      the core and the matrix, corresponding respectively to the electron-dense core
      and the electron-lucent space between the core and the vesicle membrane in osmium
      tetroxide fixations. The sizes of both compartments are inversely related, i.e.,
      the smaller the core, the larger the matrix and vice versa. The core even
      disappears, giving way to a small electron-lucent vesicle made exclusively by the
      matrix. Thus, the matrix is a constant component of the vesicle, whereas the core
      is a transient one. Each compartment has a different pool of amine: a loosely
      bound, easily releasable pool in the matrix and a tightly bound, more resistant
      pool in the core. These two pools subserve, respectively, a tonic or phasic
      release of the neurotransmitter, correlated with a tonic or phasic stimulation of
      the receptor. The core may be considered as a storage or reserve pool.
      Experimental evidence from our laboratory supports the concept that different
      mechanisms are operative in both compartments in the release of the
      neurotransmitter. For instance, a Ca2(+)-independent release would be primarily
      concerned with the neurotransmitter contained in the matrix, and a Ca2(+)
      dependent efflux would be primarily related with the neurotransmitter stored in
      the core. However, it still must be established that a simple relationship exists
      between each kind of stimulus and each vesicle compartment, rather than both
      compartments being integrated in a dynamic functional unit.

PMID- 1363048
TI  - In search of synaptosomal Na+,K(+)-ATPase regulators.
AB  - The arrival of the nerve impulse to the nerve endings leads to a series of events
      involving the entry of sodium and the exit of potassium. Restoration of ionic
      equilibria of sodium and potassium through the membrane is carried out by the
      sodium/potassium pump, that is the enzyme Na+,K(+)-ATPase. This is a particle
      bound enzyme that concentrates in the nerve ending or synaptosomal membranes. The
      activity of Na+,K(+)-ATPase is essential for the maintenance of numerous
      reactions, as demonstrated in the isolated synaptosomes. This lends interest to
      the knowledge of the possible regulatory mechanisms of Na+,K(+)-ATPase activity
      in the synaptic region. The aim of this review is to summarize the results
      obtained in the author's laboratory, that refer to the effect of
      neurotransmitters and endogenous substances on Na+,K(+)-ATPase activity. Mention
      is also made of results in the field obtained in other laboratories. Evidence
      showing that brain Na+,K(+)-ATPase activity may be modified by certain
      neurotransmitters and insulin have been presented. The type of change produced by
      noradrenaline, dopamine, and serotonin on synaptosomal membrane Na+,K(+)-ATPase
      was found to depend on the presence or absence of a soluble brain fraction. The
      soluble brain fraction itself was able to stimulate or inhibit the enzyme, an
      effect that was dependent in turn on the time elapsed between preparation and use
      of the fraction. The filtration of soluble brain fraction through Sephadex G-50
      allowed the separation of two active subfractions: peaks I and II. Peak I
      increased Na+,K(+)- and Mg(2+)-ATPases, and peak II inhibited Na+,K(+)-ATPase.
      Other membrane enzymes such as acetylcholinesterase and 5'-nucleotidase were
      unchanged by peaks I or II. In normotensive anesthetized rats, water and sodium
      excretion were not modified by peak I but were increased by peak II, thus
      resembling ouabain effects. 3H-ouabain binding was unchanged by peak I but
      decreased by peak II in some areas of the CNS assayed by quantitative
      autoradiography and in synaptosomal membranes assayed by a filtration technique.
      The effects of peak I and II on Na+,K(+)-ATPase were reversed by catecholamines.
      The extent of Na+,K(+)-ATPase inhibition by peak II was dependent on K+
      concentration, thus suggesting an interference with the K+ site of the enzyme.
      Peak II was able to induce the release of neurotransmitter stored in the synaptic
      vesicles in a way similar to ouabain. Taking into account that peak II inhibits
      only Na+,N(+)-ATPase, increases diuresis and natriuresis, blocks high affinity 3H
      ouabain binding, and induces neurotransmitter release, it is suggested that it
      contains an ouabain-like substance.

PMID- 1363049
TI  - Insulin insensitivity in nonobese, nondiabetic essential hypertension and its
      improvement by an alpha 1-blocker (bunazosin).
AB  - To investigate insulin insensitivity and its reversibility, we performed an
      insulin sensitivity test using the steady state plasma glucose (SSPG) method in
      10 lean hypertensive subjects with normal glucose tolerance before and after
      treatment with alpha 1-blocker bunazosin, and 14 age body mass index-adjusted
      healthy control subjects. Steady state plasma glucose was significantly higher in
      the hypertensive subjects compared with the control group (182 +/- 10 mg/dL v 104
      +/- 7, P < .01, mean +/- standard error of the mean (SEM). Steady state plasma
      glucose significantly decreased to 136 +/- 12 mg/dL (P < .01) after the treatment
      with alpha 1-blocker bunazosin, with a decrease of blood pressure. Hypertensive
      subjects had shown an increased area under the curve of glucose and insulin
      during the oral glucose tolerance test compared with normal controls. The glucose
      area decreased significantly, but the insulin area did not change after the
      treatment. There was no difference in plasma epinephrine, norepinephrine, and
      fractional excretion of Na between normal and hypertensive subjects both before
      and after treatment with bunazosin at basal and during insulin sensitivity tests
      (2 h). Serum total cholesterol level decreased and HDL cholesterol increased
      significantly after treatment with bunazosin. A significant correlation was
      observed between SSPG and blood pressure, but not between insulin level and blood
      pressure. The results indicate that insulin sensitivity is better related than
      hyperinsulinemia to hypertension and that this insensitivity is partially
      reversible by alpha 1-blocker, bunazosin.

PMID- 1363050
TI  - The mechanism of perturbation in monoamine metabolism by L-dopa therapy: in vivo
      and in vitro studies.
AB  - In the cerebrospinal fluid of the patients with Parkinson's disease treated with
      L-DOPA, L-3-O-methyldopa was the major metabolite of administered L-DOPA. Using a
      dopaminergic cell model, clonal rat phenochromocytoma PC 12h cells, and by
      microdialysis of the rat striatum it was proved that L-3-O-methyldopa was taken
      up into monoamine neurons by transport system specific for aromatic L-amino acids
      and inhibited transport of L-DOPA and other amino acids competitively. L-3-O
      Methyldopa depleted allosteric regulation of the biopterin cofactor on activity
      of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis.
      Depletion of the allostery may perturb the buffer action of endogenous L-DOPA
      synthesis that stabilizes dopamine level in the brain. By these mechanisms L-3-O
      methyldopa may reduce clinical effectiveness of administered L-DOPA and be
      involved in wearing-off phenomenon. L-DOPA inhibited the activity of tryptophan
      hydroxylase and thus serotonin synthesis, which may be related to psychiatric
      side-effects in the patients under L-DOPA therapy.

PMID- 1363051
TI  - Differential locomotor interactions between dopamine D1/D2 receptor agonists and
      the NMDA antagonist dizocilpine in monoamine-depleted mice.
AB  - Previous work in our laboratory has shown that the non-competitive N-methyl-D
      aspartate antagonist dizocilipine (MK-801) interacts synergistically with the
      mixed dopamine (DA) receptor agonist apomorphine and the DA D 1 agonist SKF 38393
      to promote locomotion in monoamine-depleted mice. The purpose of the present
      study was to compare the roles of DA D 1 and DA D 2 receptors in this
      interaction. To that end, dizocilpine was given in combination with either the DA
      D 1 receptor agonist SKF 38393 or the selective DA D 2 receptor agonist
      quinpirole or the preferential DA D 2 agonist bromocriptine. In general, the
      locomotor stimulatory effects produced by SKF 38393 were potentiated by
      dizocilpine, whereas the locomotor stimulation produced by quinpirole and
      bromocriptine was counteracted. However, baseline activity, which partly depends
      on how much time is allowed to elapse between administration of the DA agonist
      and commencement of locomotor recording, and partly on the dose of the DA
      agonist, seems to be an important factor that determines whether dizocilpine will
      have a weakening or a potentiating effect. Interestingly, the competitive NMDA
      antagonist D-CPPene displayed a different pattern of interaction with SKF 38393
      and quinpirole in that synergistic effects were observed with both DA agonists,
      most conspicuously so with the DA D 2 receptor agonist. The results are
      interpreted in the light of present knowledge of basal ganglia neuroanatomy; they
      are discussed in relation to the "direct" and "indirect" pathways from the
      striatum to the thalamus, proposed to form part of positive and negative cortico
      striato-thalamo-cortical loops, respectively, as well as to the presumed
      presynaptic D 2 receptors on corticostriatal glutamatergic neurons.

PMID- 1363052
TI  - Torsion of a malignant undescended testis mimicking appendicitis.
AB  - Testicular maldescent is known to be associated with later development of
      malignancy. The maldescended testis is prone to other complications--in
      particular, torsion. We report an unusual coincidence of both malignancy and
      torsion of an intra-abdominal testis which closely simulated a ruptured appendix
      abscess. This case demonstrates that an intra-abdominal testis can develop acute
      life-threatening complications which should be considered in any patient with
      acute abdominal symptoms who has an 'absent' testis.

PMID- 1363053
TI  - Efficacy of stellate ganglion block: a clinical study with bupivacaine.
AB  - BACKGROUND AND OBJECTIVES: When administering stellate ganglion blocks (e.g., to
      pain patients), it may be essential to know whether the sympathetic block is
      complete. The aim of the present study was to study the efficacy of stellate
      ganglion blocks using different concentrations and volumes of local anesthetic
      and different sites of injection. METHODS: Fifty-four stellate ganglion blocks
      (cervicothoracic sympathetic blocks) were performed for relief of chronic pain in
      30 patients, all with a pre-block palmar skin temperature 32 degrees C or lower.
      Bupivacaine in random combinations of concentration (high, 5 mg/ml; low, 2.5
      mg/ml), volume (high, 15-20 ml; low, 5-10 ml), and site of injection (C6 or C7)
      was used. The efficacy of these combinations was assessed by registering the
      following changes in effector organ activity: (1) observed signs (e.g., Horner's
      syndrome: miosis, ptosis, enophthalmos, and reddening of the sclera) and (2)
      objective measurements of changes in skin temperature, skin blood flow (laser
      Doppler flowmetry), skin resistance response, and in skin resistance level.
      RESULTS: Only 15 of 54 blocks met four of the five criteria for an effective
      block: a Horner's syndrome in combination with an increased skin temperature (to
      > or = 34 degrees C), increased skin blood flow ( > or = 50%), and completely
      abolished skin resistance response on both the radial and the ulnar sides of the
      blocked hand. Only six of those 54 met all five criteria: they also had an
      increase ( > or = 13%) in skin resistance level on the radial and ulnar sides.
      Injection toward C7 instead of injection toward C6, and high concentration
      instead of low, seemed to be more advantageous, whereas volume seemed to be of
      less importance. A relationship between pre-block skin temperature and the rise
      in temperature during the block was found. CONCLUSIONS: It was difficult to
      achieve a block that met all five established criteria. When assessing the
      efficacy of a stellate ganglion block, it is essential to evaluate the effects on
      vasoconstrictor and sudomotor fibers.

PMID- 1363054
TI  - A co-stimulatory role for CD28 in the activation of CD4+ T lymphocytes by
      staphylococcal enterotoxin B.
AB  - In this study we investigated the differential effect of the co-stimulatory
      receptor ligand molecules CD2/LFA-3, LFA-1/ICAM-1, and CD28/B7 on microbial
      superantigen mediated activation of CD4+ T cells. Highly purified CD4+ T cells,
      depleted of antigen presenting cells (APCs), do not proliferate in response to
      the superantigen, staphylococcal enterotoxin B (SEB). However, CD4+ T cells do
      respond to SEB in the presence of the LFA-3, ICAM-1, and B7 positive
      erythroleukemic cell line K562, murine L cells, human B7 transfected L cells or
      CD28 mAb. The K562 plus SEB induced response can be inhibited by combinations of
      mAbs to CD2 and LFA-1, and to LFA-3, ICAM-1, and B7. Addition of CD28 mAb to the
      CD2 and LFA-1 inhibited cultures could restore the response. Furthermore, soluble
      CD28 mAb alone is able to synergize with SEB to induce a proliferative CD4+ T
      cell response. CD4+ T cells depleted of APCs could also be activated by a pool of
      four mAbs directed to the V beta 5, V beta 6, V beta 8, and V beta 12 region of
      the TCR when a co-stimulatory signal was provided by the CD28 mAb, while the V
      beta mAbs alone or in combination are unable to activate CD4+ T cells in the
      absence of APCs. In contrast, addition of soluble mAbs to CD2 and LFA-1 molecules
      failed to co-stimulate SEB activated CD4+ T lymphocytes. The kinetics of the
      different modes of activation are distinct. SEB induced proliferation is most
      efficient in the presence of autologous APCs with maximal proliferation at a log4
      lower SEB concentration than when CD28 mAbs were used. SEB plus K562 activation
      peaks on day 7, while SEB plus CD28 mAb induced proliferative responses do not
      peak until day 9. Thus, superantigen mediated activation of CD4+ T cells requires
      co-stimulatory signals, among which CD28 has distinct and unique effects.

PMID- 1363055
TI  - Life and death of a superantigen-reactive human CD4+ T cell clone: staphylococcal
      enterotoxins induce death by apoptosis but simultaneously trigger a proliferative
      response in the presence of HLA-DR+ antigen-presenting cells.
AB  - We report that a human CD4+ T cell clone with specificity for staphylococcal
      enterotoxin (SE) superantigens A, D, and E can respond to SEs in two seemingly
      opposite ways. In the absence of antigen presenting cells (APC), SEA, D, and E
      (but not SEB or C1) strongly inhibited in a dose-dependent manner the
      responsiveness of clone D894/25 to exogenous IL-2. Growth inhibition was due to
      SE-induced programmed cell death (apoptosis) as shown by propidium iodide
      staining and the appearance of the characteristic ladder pattern of DNA
      fragmentation. Apoptotic cell death was accompanied by significant cell lysis
      after 4 and 8 h as measured in a 51Cr release assay. In contrast (but as
      expected), a proliferative response of clone D894/25 was triggered by SEA, D, and
      E in the absence of exogenous IL-2 but presence of HLA class II-positive
      lymphoblastoid cell line (LCL) as APC. Moreover, the addition of LCL feeder cells
      partially prevented the suppression of IL-2 responsiveness by SEs. Surprisingly,
      however, the latter two culture conditions (i.e. presence of LCL feeder cells
      with or without exogenous IL-2) were associated with similar levels of induced
      cell death as in the absence of LCL. At the clonal level, these data demonstrate
      that SE superantigens induce programmed cell death in a fraction (40-50%) of
      responsive mature T cells, irrespective of the presence or absence of MHC class
      II-positive APC. We conclude that the proliferative response of clone D894/25
      which is triggered by SEs in the presence of APC and absence of IL-2 must
      originate from the fraction (50-60%) of clone T cells surviving SE-induced cell
      death.

PMID- 1363056
TI  - Abnormal distribution of IL-6 receptor in aged MRL/lpr mice: elevated expression
      on B cells and absence on CD4+ cells.
AB  - A mAb against murine IL-6 receptor (IL-6R), KMH7, was obtained by immunization of
      hamster with recombinant soluble murine IL-6R. Flow cytometry analysis of IL-6R
      distribution on lymphocytes in BALB/c showed that IL-6R was expressed on
      peripheral lymph node (LN) T cells of either CD4+ or CD8+ phenotype, and Peyer's
      patch IgA+ B cells, but not on splenic B cells and thymocytes. A similar
      distribution was observed in 5 week old MRL/lpr and 16-week-old MRL/n mice. In
      contrast, in 16 week old MRL/lpr mice of both sexes, IL-6R was expressed on
      splenic IgM+ cells. Peripheral LN CD4+ T cells in 16 week old female MRL/lpr mice
      did not express IL-6R. Thymocytes in any population with a phenotype of CD4+ or
      CD8+, double negative, and double positive were not stained with KMH7 in both
      BALB/c and MRL/lpr mice. In both strains, IL-6R was induced in CD4+ or CD8+
      thymocytes after 2 days of culture, suggesting that CD4+ thymocytes in MRL/lpr
      have a potential to express IL-6R. Our results suggest that overexpression of IL
      6R on B cells and absence of IL-6R on peripheral CD4+ cells are concurrent with,
      or may contribute to, B cell hyperreactivity and T cell abnormality in this
      strain.

PMID- 1363057
TI  - Alpha 2-adrenoceptor control of ion and water transport in the newt renal distal
      tubule.
AB  - To study the nature of adrenergic stimulation of ions and water reabsorption in
      the newt renal distal tubule, stationary microperfusion of the nephron and
      electron probe analysis were used. After application of norepinephrine (NE 10(-6)
      M) to the tubule surface, the fractional reabsorption of fluid increased from
      15.0 +/- 3.1 to 41.30 +/- 10.4% (n = 7, p < 0.01), of Na+ from 69.30 +/- 6.6 to
      79.10 +/- 7.5% (p < 0.05), Cl- from 63.30 +/- 7.6 to 72.40 +/- 7.9% (p < 0.05).
      Instead of secretion (control), there was reabsorption of K+. Fractional
      reabsorption of Ca2+ decreased from 51.00 +/- 6.0 to 43.00 +/- 7.0% (p < 0.05).
      The nonspecific alpha-adrenergic antagonist dibenamine 10(-6) M completely
      inhibited the effect of NE while, under the action of propranolol (2 x 10(-6) M)
      NE increased ion and water reabsorption significantly. When applied alone, or
      with NE, the specific alpha 2-adrenoblocker idazoxan, 2 x 10(-6) M, did not
      interfere with reabsorption in the distal tubule. At the same time, under the
      action of alpha 1-adrenoblocker prazosin 2 x 10(-6) M NE, increased the
      fractional reabsorption of fluid from 24.10 +/- 3.4 to 44.40 +/- 4.0% (n = 6, p <
      0.001). These results serve as evidence that there exist specific alpha 2
      adrenoceptors in the newt distal tubule the stimulation of which increases
      membrane permeability of the distal tubule to water, Na+, K+, Cl-, but not to
      Ca2+.

PMID- 1363058
TI  - Comparison of the potency of five potential beta-adrenoceptor blocking drugs and
      eight calcium channel blockers to inhibit platelet aggregation and to perturb
      liposomal membranes prepared from platelet lipids.
AB  - Five potential beta-adrenoceptor blocking (BAB) compounds, alkylesters of 4-[(2
      hydroxy-3-alkylamino)propoxy] phenylcarbamic acid, and eight calcium channel
      blockers (CB), i.e. nifedipine, nimodipine, niludipine, nitrendipine, verapamil,
      gallopamil, mepamil and diltiazem, were compared as to their inhibitory effect on
      thrombin induced aggregation of washed rat platelets and their effect on
      dynamics/disorder of liposomal membranes prepared from platelet lipids, studied
      by EPR spectroscopy of a lipid spin probe. The anti-aggregatory potency of the
      BAB and CB drugs was effective within the concentration range of 0.01-1 mmol/l.
      The antiaggregatory potency of BAB increased in the order BL-143 < BL-243 < BL
      343 < BL-443 < BL-543 and among the CB, nifedipine and diltiazem were least
      potent, whereas nitrendipine and mepamil were the most potent drugs. The potency
      of the other CB tested was intermediate. The BAB drugs increased the
      dynamics/disorder of the liposomes in the same order as they inhibited platelet
      aggregation, whereas there was no relationship between antiaggregatory effect of
      CB and their influence on dynamics/disorder of the liposomes. Nifedipine,
      nimodipine, niludipine and nitrendipine had a minor perturbation effect on the
      liposomes, whereas verapamil, mepamil, gallopamil and diltiazem pronouncedly
      increased the dynamics/disorder of the hydrophobic part of the liposomes. The
      results indicate that the anti-aggregatory activity of BAB drugs may be mediated,
      at least partially, through their perturbation effect on the lipid part of
      biological membranes.

PMID- 1363059
TI  - Pancytopaenia and hepatosplenomegaly in an AIDS patient responding to high dose
      steroids.

PMID- 1363060
TI  - Disposition of human drug preparations in the horse. II. Orally administered
      fencamfamine.
AB  - A gas chromatographic method to measure urinary levels of the central nervous
      system stimulant fencamfamine and some of its metabolites is described. When 100
      mg fencamfamine was given orally to four horses the parent drug could not be
      detected in the urine. After enzymatic hydrolysis of the urine the major human
      metabolite, N-desethylated fencamfamine, only accounted for 1% of the dose in 12
      h. The major equine metabolites were conjugated parahydroxylated compounds
      representing 18% of the dose. With regard to horse doping control and analysis,
      the injudicious use of human doping routine methods for the detection of
      fencamfamine in equine urine could lead to false negative results.

PMID- 1363061
TI  - Comparative investigation of disposition of 3,4-(methylenedioxy)methamphetamine
      (MDMA) in the rat and the mouse by a capillary gas chromatography-mass
      spectrometry assay based on perfluorotributylamine-enhanced ammonia positive ion
      chemical ionization.
AB  - A gas chromatography-mass spectrometry assay based on perfluorotributylamine
      enhanced ammonia positive ion chemical ionization has been developed for MDMA and
      three of its primary metabolites in biological specimens; the assay is linear
      from 2 to 1000 ng ml-1. Quantitatively, more of an administered dose of 10 mg kg
      1 MDMA was excreted by the mouse (72%) than by the rat (35%); most in both
      species was excreted in urine and within 24 h. The difference in per cent
      excretion is entirely due to proportionally greater excretion of the parent drug
      by the mouse. 4-Hydroxy-3-methoxymethamphetamine (HMM) is the major urinary
      metabolite in both species. HMM and another primary metabolite, 4-hydroxy-3
      methoxyamphetamine (HMA), were excreted mainly as glucuronide and sulphate
      conjugates (> 85%).

PMID- 1363062
TI  - Papillary thyroid carcinoma: a multivariate analysis of prognostic factors
      including an evaluation of the p-TNM staging system.
AB  - OBJECTIVE: To analyse the prognostic factors in papillary thyroid carcinoma, and
      in particular to evaluate the accuracy of the pathological tumour, nodes,
      metastases (p-TNM) staging. DESIGN: Retrospective univariate and multivariate
      analysis. SETTING: University hospital in Norway. SUBJECTS: 167 patients who were
      operated on for papillary thyroid carcinoma between 1971 and 1985. Main outcome
      measures--Death of papillary thyroid carcinoma, and length of recurrence free
      survival. RESULTS: Male sex, increasing age, larger tumours, and spread of growth
      beyond the thyroid all independently increased the risk of dying of papillary
      thyroid carcinoma, whereas the period of recurrence free survival was influenced
      only by the presence of regional metastases and the patient's age. The age
      related p-TNM staging is suitable for predicting the likelihood of death, but is
      less accurate in the prediction of recurrence free survival. The age of 45 years
      is too low to be useful in predicting survival, especially in women. CONCLUSION:
      The identification of sex in the multivariate analysis as a strong independent
      predictor of death of papillary thyroid cancer suggests that the prognostic value
      of the age related p-TNM staging system could be improved if sex was adjusted
      for, and if a different age was used for men and women.

PMID- 1363063
TI  - Herniorrhaphy in patients aged 80 years or more. A prospective analysis of
      morbidity and mortality.
AB  - OBJECTIVE: To find out the morbidity and mortality after repair of groin hernias
      in patients aged 80 years or more, and to identify factors that add to the risk
      of hernia repair. DESIGN: Prospective open study. SETTING: All general surgical
      departments in Ringkobing County, Denmark. SUBJECTS: All 39 patients aged 80
      years and over who were admitted with hernias during a one year period (1990).
      OUTCOME MEASURES: Morbidity and mortality. RESULTS: Three patients refused
      operation, and of the remaining 36, 15 (42%) were admitted as emergencies (5 of
      whom were already waiting for elective repair of their hernias). The median age
      was 84 years (range 80-90) and 23 (64%) were men, 31 patients had inguinal
      hernias, 4 had femoral hernias, and one an obturator hernia. There were six major
      and two minor complications after 14 emergency operations (57%), and one minor
      complication after 22 elective operations (5%, p = 0.0007). Two patients died,
      both after emergency operations (14%). CONCLUSION: Elective hernia repair can be
      carried out safely even in the presence of serious coexisting disease, and
      emergency hernia repair carries a high risk of complications even in the absence
      of coexisting disease.

PMID- 1363064
TI  - Effects of jejunoileal bypass on oxalate and mineral metabolism in rats.
AB  - OBJECTIVE: To reassess the effects of jejunoileal bypass on the gastrointestinal
      absorption and bone metabolism of certain minerals in rats, and to see if
      jejunoileal bypass in rats was a suitable model in which to study formation of
      calcium oxalate renal stones. DESIGN: Controlled study. SETTING: Division of
      Experimental Surgery, University of Erlangen, Germany. MATERIAL: 43 male Sprague
      Dawley rats. INTERVENTION: 23 rate underwent jejunoileal bypass, and 20
      laparotomy, with transsection and anastomosis of the jejunum and ileotomy and
      suture (sham operation). RESULTS: Rats that had undergone jejunoileal bypass ate
      less and gained less weight than those that had had sham operations. Absorption
      of calcium and phosphorus from the intestine was impaired, but that of magnesium
      was unchanged. Absorption of oxalate from the small intestine was unchanged, but
      that from the colon was increased. There were no signs of hyperoxaluria or
      urolithiasis. Serum mineral homeostasis was not affected by jejunoileal bypass
      nor were bone volume, density, or mineral concentrations. Serum concentrations of
      parathyroid hormone and 1,25-dihydroxycholecalciferol remained low, suggesting
      that jejunoileal bypass might have induced some calcium flux towards the vascular
      space. CONCLUSIONS: Jejunoileal bypass halts weight increase in rats; the model
      may be helpful in elucidating associations between enteric factors and
      calciotropic hormones, and several metabolic features that are altered by
      jejunoileal bypass in man are not altered in rats.

PMID- 1363065
TI  - Acute appendicitis in pregnancy: complications and subsequent management.
AB  - OBJECTIVE: To establish guidelines for the management of a pregnancy that is
      complicated by acute appendicitis. DESIGN: Retrospective study. SETTING:
      University Hospital, Copenhagen, Denmark. SUBJECTS: 16 patients operated on for
      symptoms of acute appendicitis during the 15 year period 1974-1988. RESULTS: In
      12 patients (75%) the diagnosis was confirmed histologically. The signs and
      symptoms were classic, and three patients had contractions. One fetus died, in a
      patient with appendicitis complicated by intraperitoneal abscess. In all
      uncomplicated cases the pregnancy proceeded to term and the deliveries were
      normal. CONCLUSIONS: Pregnancy should not deter a surgeon from removing an
      appendix, once the diagnosis is suspected; no pregnancy was affected by removal
      of a normal appendix. We recommend that prophylactic antibiotics and tocolytic
      drugs be given in all cases. Simultaneous caesarean section should be done only
      if there are obstetric indications.

PMID- 1363066
TI  - Colonic volvulus. Diagnosis and results of treatment in 82 patients.
AB  - OBJECTIVE: To test the accuracy of initial diagnosis of colonic volvulus and the
      results of different treatment regimens. DESIGN: Retrospective population based
      study. SETTING: Tampere University Hospital (major referral center). SUBJECTS:
      All patients who presented with colonic volvulus from 1973-1990, 58 patients had
      sigmoid, 23 caecal and one had transverse colonic volvulus. MAIN OUTCOME
      MEASURES: Findings of endoscopic or operative treatment compared with the
      clinical diagnosis and plain abdominal radiographs. Association between treatment
      and risk factors. RESULTS: Diagnosis was difficult, despite some differences in
      clinical presentation. Gangrenous bowel was diagnosed only at operation, although
      caecal volvulus with gangrenous bowel was associated with a high white cell
      count. In 23 patients with caecal volvulus both right hemicolectomy (n = 11) and
      tube caecostomy (n = 7) were successful with one death after each procedure and
      no recurrences. In sigmoid volvulus, resection (n = 19) and detorsion with or
      without sigmoidopexy (n = 21) resulted in similar numbers of complications and
      deaths (6 and 4, and 5 and 3, respectively), though recurrences were more common
      after detorsion (1 (5%) compared with 5 (24%)). Endoscopic decompression was
      tried in 30 and was successful in 26 cases; it was the only treatment in 17/58
      patients, with two deaths (12%) and five recurrences (29%). The overall mortality
      was 15%, but this was associated more with neuropsychiatric diseases, old age,
      and residence in mental or nursing homes than with gangrene of the bowel.
      CONCLUSIONS: Poor diagnostic accuracy is a problem. Caecal volvulus can be safely
      treated by resection or tube caecostomy. Sigmoid volvulus is best treated by
      endoscopic detorsion followed by operation in otherwise fit patients. Mortality
      is associated with neuropsychiatric diseases and old age.

PMID- 1363067
TI  - New method for the internal stabilisation of flail chest.

PMID- 1363069
TI  - Exteriorisation of small bowel anastomosis alternative to a double stoma.

PMID- 1363068
TI  - Pancreaticoduodenal resection including the portion developed from the ventral
      embryonic bud.

PMID- 1363070
TI  - Rupture of the vein patch: a serious complication of profundaplasty.

PMID- 1363071
TI  - Chylous ascites after aortic replacement.

PMID- 1363072
TI  - Vertebral arteriovenous fistula caused by puncture of the internal jugular vein.

PMID- 1363073
TI  - Myelolipoma of the adrenal gland. Report on two cases.

PMID- 1363074
TI  - Hemodynamic observation and treatment approach for patients with angina
      decubitus.
AB  - In order to investigate the mechanism and treatment of angina decubitus, 20
      patients (18 men and 2 women aged 36-70 years) were studied during
      hospitalization. All patients were found to have an increased heart rate x
      systolic blood pressure product before the onset of angina decubitus, indicating
      that this type of angina pectoris belongs to the category of effort angina. Of
      the 11 patients investigated by continuous hemodynamic monitoring, 3 had
      significant progressive increases in pulmonary artery systolic pressure (PASP)
      and pulmonary artery diastolic pressure (PADP) before onset: their episodes of
      angina could not be completely controlled by digoxin and diuretics, but quickly
      subsided after beta blockers were added. Among the other 8 patients, PADP
      increased slightly in 5 and remained unchanged in 3 cases before onset: these
      patients had no manifestations of LV dysfunction, and beta blockers combined with
      coronary vasodilators produced satisfactory effects. These results indicate that
      LV failure is not a major factor in the pathogenesis of angina decubitus. The LV
      diastolic dysfunction seen in 8/11 cases may have been related to LV hypertrophy
      caused by long-term hypertension or chronic persistent ischemia.

PMID- 1363075
TI  - The Cellular and Molecular Basis of the Platelet Storage Lesion. Papers of a
      symposium. Bethesda, Maryland, April 1991.

PMID- 1363076
TI  - Regulation of anterior cell-specific mec-3 expression during asymmetric cell
      division in C. elegans.
AB  - The homeobox-containing mec-3 gene of C. elegans is expressed in 10
      mechanosensory neurons and is necessary for these cells to acquire their fate.
      All the mec-3-expressing cells are anterior daughters from an asymmetric cell
      division. In this paper, we examine the expression of a mec-3--lacZ fusion in the
      presence of mutations that may disrupt asymmetric cell division or anterior
      posterior positional information, as well as mutations that may specifically
      alter mec-3 expression. A mutation in lin-17 causes production of additional mec
      3-expressing cells and can have its effect on the cell division that produces a
      mec-3-expressing cell. In a lin-5 mutant, in which postembryonic blast cells do
      not complete cell division and become polyploid, blast cells that would give rise
      to mec-3-expressing daughters instead express mec-3 themselves. In a lin-12 glp-1
      double mutant, which is disrupted for many cell interactions in which two cells
      compete for the same fate, mec-3 expression is unaffected. These results are
      consistent with a model for asymmetric cell division in which the mec-3
      expressing cell and its sister are different immediately upon cell division,
      rather than acquiring differences through later interaction with each other or
      their surroundings. lin-17 mutant animals also show defects in the position of
      the PVM cell and the PLM axons. Animals mutant in unc-73 and unc-40, known to
      have axon outgrowth defects, also show errors in PVM position and a low frequency
      of additional mec-3-expressing cells, as well as occasional secondary vulval
      protrusions, a common phenotype of lin-17 animals. Many other mutations have
      either no effect on mec-3 expression or an effect that can be largely predicted
      from previously known phenotypes: these include mab-5, mig-1, unc-53, egl-5, lin
      32, and egl-27. unc-11 shows an unexpected and specific defect in mec-3
      expression in the PVD neurons, but not in the other mec-3-expressing cells. Two
      mutations that suppress the egg-laying defect of unc-86 have no effect on the mec
      3 expression defect in an unc-86 mutant.

PMID- 1363077
TI  - Pericholangitis with ulcerative colitis following autoimmune hepatitis over 12
      years.
AB  - A 35-year-old woman was diagnosed as autoimmune hepatitis 12 years ago by
      abnormal findings of liver tests including lupus erythematosus (LE) cell
      phenomenon and liver biopsy. She was admitted in May 1990 with a history of lower
      gastrointestinal bleeding. Colonoscopy with biopsy and barium enema revealed
      chronic ulcerative colitis along the entire colon. Since liver tests did not
      respond well to prednisolone treatment, liver biopsy was again performed and it
      revealed periductal inflammation with small duct proliferation, a finding
      compatible with pericholangitis. We herein report this patient who was initially
      diagnosed as autoimmune hepatitis and thereafter found to be pericholangitis
      associated with ulcerative colitis.

PMID- 1363078
TI  - Dapiprazole: will it affect the standard of care for pupillary dilation?
AB  - One of the most controversial clinical issues in optometry is the use of
      "routine" pupillary dilation. Many optometrists are still reluctant to employ
      routine dilation because of concerns regarding patient inconvenience, angle
      closure glaucoma, or systemic side effects. Dapiprazole, a new alpha-adrenergic
      blocking agent, is now available to reverse the effects of tropicamide- or
      phenylephrine-induced mydriasis. This article discusses the advantages, clinical
      uses, limitations, and legal aspects of this mydriatic antagonist in optometric
      practice.

PMID- 1363079
TI  - Drug therapy for ocular allergy.
AB  - Ocular allergy is a common problem for the primary care practitioner. A range of
      ocular decongestants, antihistamines, mast cell stabilizers, and corticosteroids
      are available for use, and practitioners must be familiar with the clinical
      effectiveness, treatment regimens, and side effects of these drugs. This paper
      reviews the drugs, both prescription and nonprescription, appropriate for
      management of ocular allergy and provides guidelines for their use.

PMID- 1363080
TI  - Ocular side effects of selected systemic drugs.
AB  - Numerous systemic drugs produce adverse effects that involve the eye. Pigmentary
      inclusions of the lids or conjunctivae or both may be caused by a variety of
      drugs, including amiodarone, chlorpromazine, and gold salts, while conjunctivitis
      and blepharoconjunctivitis have been associated with isotretinoin, sulfonamides,
      salicylates, and antineoplastic agents. Dry eye complaints may be caused by
      antihistamines, beta-receptor blocking agents prescribed for cardiovascular
      problems, antianxiety agents, and tricyclic antidepressants. Several drugs have
      been well documented as causes of keratopathies and/or lenticular deposits,
      including chloroquine and hydroxychloroquine, chlorpromazine, gold salts,
      systemic corticosteroids, nonsteroidal antiinflammatory drugs, and the
      antiarrhythmic agent amiodarone. Visual acuity may be decreased by transient
      changes in refractive error caused by sulfonamides, the antifungal agent
      metronidazole, thiazide diuretics, and carbonic anhydrase inhibitors. Dilation of
      the pupil may be caused by anticholinergic drugs, antihistamines, antidepressant
      agents, and central nervous system stimulants such as cocaine, methylphenidate,
      and amphetamines. Nystagmus, diplopia, and extraocular muscle palsies have been
      associated with central nervous system depressants, antihistamines, barbiturates,
      and elevated blood ethanol concentrations. Intraocular pressure can be elevated
      in susceptible individuals by long-term use of topical or systemic
      corticosteroids. Numerous drugs have been associated with retinal toxicity,
      including chloroquine and hydroxychloroquine, thioridazine, tamoxifen, and talc,
      which may embolize to the retinal circulation when administered by long-term drug
      abusers. The antituberculosis agents ethambutol and isoniazid have been
      implicated as causes of reduced acuity, visual field defects, and disturbances of
      color vision. Optic neuritis and retrobulbar neuritis may result from the use of
      chloramphenicol. This paper describes these and other adverse ocular effects that
      may be encountered when examining patients who are taking systemic drugs.

PMID- 1363081
TI  - "Brenda goes to town". A case study of a woman with agoraphobia.

PMID- 1363082
TI  - Long-term effects of befunolol on the corneal endothelium and the consensual
      ophthalmotonic reaction.
AB  - In a double-blind study, 30 patients with ocular hypertension were randomly
      assigned to receive one drop of 0.5% befunolol or placebo (the drug vehicle) in
      each eye twice daily for 120 days. The befunolol used contained no preservatives.
      Before and after treatment the number and shape of the endothelial cells of the
      five corneal sectors were evaluated. After 120 days of twice-daily application of
      befunolol or placebo, no changes in the shape or density of the corneal cells
      were found in any patient. No differences in the patients receiving befunolol or
      placebo were noted. The consensual ophthalmotonic reaction was studied in 15 of
      the patients before and after befunolol administration. A significant decrease in
      intraocular pressure was noted at 30 minutes and at 1, 2, 3, 4, 5, and 6 hours
      after befunolol. Intraocular pressure also decreased significantly at 1 to 4
      hours after placebo, and then returned to pretreatment levels at 6 hours.

PMID- 1363083
TI  - Measurement of thyroid-stimulating immunoglobulins by incorporation of tritiated
      adenine into intact FRTL-5 cells: a viable alternative to radioimmunoassay for
      the measurement of cAMP.
AB  - OBJECTIVE: To evaluate the utility of 3H-adenine incorporation into intact rat
      thyroid epithelial cells (FRTL-5) as an alternative to radioimmunoassay for the
      measurement of cAMP following stimulation of these cells by serum thyroid
      stimulating immunoglobulins from patients with Graves' disease. DESIGN: We
      determined the cAMP produced by FRTL-5 cells following incubation with serum from
      patients with a spectrum of autoimmune thyroid and other diseases using the 3H
      adenine assay. PATIENTS: We studied 27 patients with untreated Graves' disease,
      10 with Graves' disease complicated by ophthalmopathy (all on antithyroid
      medication), 11 with Hashimoto's thyroiditis, five with multinodular goitre, one
      with thyroid carcinoma, 23 with type 1 diabetes mellitus, 19 with other
      autoimmune diseases and 10 controls. MEASUREMENTS: The 3H-cAMP produced in cells
      incubated with either bovine TSH (bTSH) or polyethylene glycol-precipitated serum
      immunoglobulins, was separated by sequential chromatography on Dowex and alumina
      columns, and counted. The thyroid-stimulating immunoglobulins index (3H-cAMP
      patient immunoglobulins/3H-cAMP control immunoglobulins) was calculated for each
      serum and considered positive if greater than 1.5 (+ve thyroid-stimulating
      immunoglobulins index, i.e. > 2 standard deviations above control). The thyroid
      stimulating immunoglobulins index was correlated with measurement of thyrotrophin
      binding inhibitory immunoglobulins (TBII) by radioreceptor assay. RESULTS: The 3H
      adenine assay has a sensitivity of 10(-11) M bTSH with maximal stimulation at 10(
      9) M bTSH (30-fold). Twenty-five of 27 patients (92%) with untreated Graves'
      disease and four of 10 patients with Graves' disease complicated by
      ophthalmopathy had +ve thyroid-stimulating immunoglobulin indices. The thyroid
      stimulating immunoglobulins index in patients with untreated Graves' disease
      correlated with their TBII assay result (r = 0.63, P < 0.001). In addition, the
      index was negative in patients with Hashimoto's thyroiditis, multinodular goitre,
      thyroid carcinoma, and type 1 diabetes mellitus. Of the patients with other
      autoimmune diseases only one (a patient with systemic lupus erythematosis) had a
      +ve thyroid-stimulating immunoglobulin index. Direct comparison of cAMP
      measurement by 3H-adenine incorporation and commercial radioimmunoassay showed an
      equal sensitivity to both bTSH and Graves' immunoglobulins. After cell
      preparation, results are obtained more quickly with the 3H-adenine assay than
      with a cAMP radioimmunoassay (5 hours compared to 2 days), and far more cheaply
      than by commercial radioimmunoassays. CONCLUSIONS: Measurement of thyroid
      stimulating immunoglobulins using the incorporation of 3H-adenine into cAMP in
      FRTL-5 cells is sensitive, reproducible, rapid and specific. These features make
      this assay a viable alternative to RIA for the measurement of thyroid-stimulating
      immunoglobulins in patients with Graves's disease.

PMID- 1363084
TI  - Why we have (only) five fingers per hand: hox genes and the evolution of paired
      limbs.
AB  - Limb development has long been a model system for studying vertebrate pattern
      formation. The advent of molecular biology has allowed the identification of some
      of the key genes that regulate limb morphogenesis. One important class of such
      genes are the homeobox-containing, or Hox genes. Understanding of the roles these
      genes play in development additionally provides insights into the evolution of
      limb pattern. Hox gene expression patterns divide the embryonic limb bud into
      five sectors along the anterior/posterior axis. The expression of specific Hox
      genes in each domain specifies the developmental fate of that region. Because
      there are only five distinct Hox-encoded domains across the limb bud there is a
      developmental constraint prohibiting the evolution of more than five different
      types of digits. The expression patterns of Hox genes in modern embryonic limb
      buds also gives clues to the shape of the ancestral fin field from which the limb
      evolved, hence elucidating the evolution of the tetrapod limb.

PMID- 1363085
TI  - Clox, a mammalian homeobox gene related to Drosophila cut, encodes DNA-binding
      regulatory proteins differentially expressed during development.
AB  - We report the isolation of a cDNA encoding a mammalian homeoprotein related to
      the Drosophila cut gene product, called Clox, for Cut like homeobox. In addition
      to the homeodomain, three 73-amino acid repeats, the so-called cut repeats, are
      also conserved between Cut and the mammalian counterpart described here. This
      conservation suggests that the cut repeat motif may define a new class of
      homeoproteins. Both cloned and endogenous Clox proteins are nuclear DNA-binding
      proteins with very similar sequence specificity. Western blot analysis revealed
      several distinct Clox protein species in a variety of tissues and cell types. The
      relative abundance of these proteins is regulated during mouse development and
      cell differentiation in culture. Interestingly, approximately 180-190 x 10(3)
      M(r) Clox proteins predominate in early embryos and are upregulated in committed
      myoblasts and chondrocytes, but downregulated upon terminal differentiation. Clox
      DNA-binding activity is correlated with the abundance of these proteins. In
      contrast, larger Clox protein species (approximately 230-250 x 10(3) M(r)) are
      detected mainly in adult tissues and in terminally differentiated cells.
      Cotransfection experiments show that Clox proteins can function as repressors of
      tissue-specific gene transcription. Thus, Clox, like their Drosophila
      counterparts, are candidate regulators of cell-fate specification in diverse
      differentiation programs.

PMID- 1363086
TI  - Identifying targets of the rough homeobox gene of Drosophila: evidence that
      rhomboid functions in eye development.
AB  - In order to identify potential target genes of the rough homeodomain protein,
      which is known to specify some aspects of the R2/R5 photoreceptor subtype in the
      Drosophila eye, we have carried out a search for enhancer trap lines whose
      expression is rough-dependent. We crossed 101 enhancer traps that are expressed
      in the developing eye into a rough mutant background, and have identified seven
      lines that have altered expression patterns. One of these putative rough target
      genes is rhomboid, a gene known to be required for dorsoventral patterning and
      development of some of the nervous system in the embryo. We have examined the
      role of rhomboid in eye development and find that, while mutant clones have only
      a subtle phenotype, ectopic expression of the gene causes the non-neuronal
      mystery cells to be transformed into photoreceptors. We propose that rhomboid is
      a part of a partially redundant network of genes that specify photoreceptor cell
      fate.

PMID- 1363087
TI  - Exogenous retinoic acid rapidly induces anterior ectopic expression of murine Hox
      2 genes in vivo.
AB  - Exogenous retinoic acid (RA) has teratogenic effects on vertebrate embryos and
      alters Hox-C gene expression in vivo and in vitro. We wish to examine whether RA
      has a role in the normal regulation of Hox-C genes, and whether altered Hox-C
      gene expression in response to RA leads to abnormal morphology. The expression of
      3' Hox-2 genes (Hox-2.9, Hox-2.8, Hox-2.6 and Hox-2.1) and a 5' gene (Hox-2.5)
      were examined by whole-mount in situ hybridization on embryos 4 hours after
      maternal administration of teratogenic doses of RA on embryonic day 7 to 9. The
      expression of the 3' Hox-2 genes was found to be ectopically induced in anterior
      regions in a stage-specific manner. The Hox-2.9 and Hox-2.8 genes were induced
      anteriorly in the neurectoderm in response to RA on day 7 but not at later
      stages. Expression of Hox-2.6 and Hox-2.1 was ectopically induced anteriorly in
      neurectoderm in response to RA on day 8. Hox-2.1 remained responsive on day 9,
      whereas Hox-2.6 was no longer responsive at this stage. The expression of the 5'
      gene Hox-2.5 was not detectably altered at any of these stages by RA treatments.
      We also examined the response of other genes whose expression is spatially
      regulated in early embryos. The expression of En-2 and Wnt-7b was not detectably
      altered by RA, whereas RAR beta expression was induced anteriorly by RA on day 7
      and 8. Krox-20 expression was reduced in a stage- and region-specific manner by
      RA. The ectopic anterior expression of Hox-2.8 and Hox-2.9 induced by RA on day 7
      was persistent to day 8, as was the altered expression of Krox-20. The altered
      pattern of expression of these genes in response to RA treatment on day 7 may be
      indicative of a transformation of anterior hindbrain to posterior hindbrain,
      specifically, a transformation of rhombomeres 1 to 3 towards rhombomere 4
      identity with an anterior expansion of rhombomere 5. The ectopic expression of
      the 3' Hox-2 genes in response to RA is consistent with a role for these genes in
      mediating the teratogenic effects of RA; the rapid response of the Hox-C genes to
      RA is consistent with a role for endogenous RA in refining 3' Hox-C gene
      expression boundaries early in development.

PMID- 1363088
TI  - Induction of labial expression in the Drosophila endoderm: response elements for
      dpp signalling and for autoregulation.
AB  - Extracellular signal proteins induce the homeotic gene labial (lab) to high
      levels of localised expression in the endoderm of Drosophila embryos. We aimed to
      identify cis-regulatory elements within the lab gene that respond to this
      induction by analysing the activity of stably integrated reporter gene
      constructs. Dissection of lab 5' flanking sequences reveals two types of response
      elements. One of these mediates lab dependent activity, providing evidence that
      lab induction in the endoderm is autoregulatory. The other element, to a large
      extent independent of lab function, responds to decapentaplegic (dpp), a signal
      molecule related to mammalian TGF-beta. Our evidence suggests that lab induction
      in the endoderm reflects coordinate action of two distinct factors one of which
      may be lab protein itself, and another whose localised activity or expression in
      the midgut depends on the dpp signal.

PMID- 1363089
TI  - Cell signals allow the expression of a pre-existent neural pattern in C. elegans.
AB  - In C. elegans, a simple pattern develops within a row of epidermal precursor
      cells, V1-V6. One cell, V5, gives rise to a neuroblast called the postdeirid
      neuroblast, while the other V cells produce epidermal cells instead. Here we
      describe experiments suggesting that in order for V5 to produce the postdeirid it
      must be in close or direct contact with neighboring V cells. Signaling between V
      cells is required for the formation of the neuroblast; however, which of the V
      cells can make a postdeirid is not determined by these signals but rather by the
      action of the homeotic lin-22 and pal-1 genes. These genes prevent V cells in
      specific body regions from responding to intercellular signals and producing
      postdeirids. This is a clear example of cell signals playing a permissive rather
      than an instructive role in neuroblast induction.

PMID- 1363090
TI  - Expression of the homeotic gene mab-5 during Caenorhabditis elegans
      embryogenesis.
AB  - mab-5 is a member of a complex of homeobox-containing genes evolutionarily
      related to the Antennapedia and bithorax complexes of Drosophila melanogaster.
      Like the homeotic genes in Drosophila, mab-5 is required in a particular region
      along the anterior-posterior body axis, and acts during postembryonic development
      to give cells in this region their characteristic identities. We have used a mab
      5-lacZ fusion integrated into the C. elegans genome to study the posterior
      specific expression of mab-5 during embryogenesis. The mab-5-lacZ fusion was
      expressed in the posterior of the embryo by 180 minutes after the first cleavage,
      indicating that the mechanisms responsible for the position-specific expression
      of mab-5-lacZ act at a relatively early stage of embryogenesis. In embryos
      homozygous for mutations in the par genes, which disrupt segregation of factors
      during early cleavages, expression of mab-5-lacZ was no longer localized to the
      posterior. This suggests that posterior-specific expression of mab-5 depends on
      the appropriate segregation of developmental factors during early embryogenesis.
      After extrusion of any blastomere of the four-cell embryo, descendants of the
      remaining three cells could still express the mab-5-lacZ fusion. In these partial
      embryos, however, the fusion was often expressed in cells scattered throughout
      the embryo, suggesting that cell-cell interactions and/or proper positioning of
      early blastomeres are required for mab-5 expression to be localized to the
      posterior.

PMID- 1363091
TI  - Sequence and embryonic expression of the murine Hox-3.5 gene.
AB  - The murine Hox-3.5 gene has been mapped and linked genomically to a position 18
      kb 3' of its most 5' locus neighbour, Hox-3.4, on chromosome 15. The sequence of
      the Hox-3.5 cDNA, together with the position of the gene within the locus, show
      it to be a paralogue of Hox-2.6, Hox-1.4 and Hox-4.2. The patterns of embryonic
      expression for the Hox-3.5 gene are examined in terms of three rules, proposed to
      relate a Hox gene's expression pattern to its position within the locus. The
      anterior boundaries of Hox-3.5 expression in the hindbrain and prevertebral
      column lie anterior to those of Hox-3.4 and all other, more 5'-located Hox-3
      genes. Within the hindbrain, the Hox-3.5 boundary is seen to lie posterior to
      that of its paralogue, Hox-2.6, by a distance equal to about the length of one
      rhombomere. Patterns of Hox-3.5 expression within the oesophagus and spinal cord,
      but not the testis, are similar to those of other Hox-3 genes, Hox-3.3 and Hox
      3.4.

PMID- 1363092
TI  - [Hormones and the levels of humoral regulation].
AB  - The problems on the place of hormones secreted by "classical" endocrine glands,
      on their relationship with other compounds that possess physiological activity,
      criteria that determine the definition "hormone" are considered in this article.
      The conception about the levels of the humoral regulatory systems that are
      organized and formed during phylogenesis and ontogenesis and provide a
      consecutive increase in their complexity and mobility of adaptation to changes of
      environment and internal conditions are substantiated on the basis of numerous
      data. The metabolites that are products of nonspecific activity of any cell of
      the multicellular organism form the first and simplest level of humoral
      regulatory organization. The next (second) level of humoral organization is also
      formed by chemically simple substances. However, these substances are specialized
      products of the secretory activity of cells and exert potent influence on the
      physiological processes. Neuroamines and regulatory peptides are applied to these
      agents, in the first place. They arise simultaneously and jointly at the first
      stage of ontogenesis. The distinctive characters of the third level of the
      humoral regulation are increased and complication of the regulatory activity
      conditioned by cooperative influences of humoral agents produced by single
      secretory elements situated outside the classical endocrine glands. The
      chemically and originally different substances causing predominantly local
      effects are attributed to these physiologically active substances. Their
      participation in general adaptive reactions as well as inclusion of classical
      hormones into hierarchy of humoral regulation signify the formation of the forth
      regulatory level that provides realization of general homeostatic reactions
      peculiar to the whole organism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363093
TI  - [Role of neuromediators in the efferent component of the trophic reflex].

PMID- 1363094
TI  - [Structure of neurohumoral influences on regulated function].

PMID- 1363095
TI  - [Types of blood circulation in healthy people: neurohumoral regulation of
      circulatory minute volume under rest conditions. Hyperkinetic type].

PMID- 1363096
TI  - Review of the Fogarty International Center Conference, NIH: peptides in health
      and disease.
AB  - Taken together, the lectures presented at this conference have amply demonstrated
      the ever growing impact of peptide research on health, in part by increasing our
      understanding of disease. This Fogarty International Conference has been
      invaluable because of the diverse backgrounds of the distinguished participants
      which it attracted. The lectures and the ensuing discussions justify the greatest
      expectations for the contribution which peptide research will make to human and
      animal health during the remainder of this century and beyond.

PMID- 1363097
TI  - Secondary prevention of coronary heart disease in patients after acute myocardial
      infarction at the Soroka Medical Center.
AB  - The records of 214 patients with acute myocardial infarction (AMI) admitted to
      Soroka Medical Center in 1989 were reviewed to assess the quality of medical
      treatment after AMI. Medical treatment was reviewed with respect to
      administration, indications, and contraindications of specific drugs. Sixty-nine
      percent of patients received suboptimal treatment with respect to aspirin and
      beta blockers, which was almost always due to undertreatment rather than
      overprescription. Only 23% of patients with mural thrombi, as shown by
      echocardiography and without contraindications to anticoagulants, received
      coumadin. Patients hospitalized in the Intensive Coronary Care Unit received
      somewhat better medical care with regard to aspirin, beta blockers and coumadin.
      Appropriate decisions whether to give or withhold thrombolytic therapy were made
      in 81% of the cases and it was given to 29% of the patients. We conclude that
      during the period of this study there was a considerable gap between: a)
      recommendations in the medical literature, and b) the quality of care provided to
      AMI patients with regard to medications prescribed by physicians for preventive
      medical therapy.

PMID- 1363099
TI  - Peripheral blood stem cell mobilization by cytokines.
AB  - Hematopoietic stem cells circulate in the peripheral blood. These cells can be
      collected by apheresis techniques either in the unperturbed state, after
      mobilization following the administration of cytokines like G-CSF or GM-CSF, or
      during the phase of early blood count recovery following chemotherapy-induced
      myelosuppression. The number of cells collected following mobilization is greater
      than that obtained after apheresis in the unperturbed state. There are, however,
      qualitative differences between unperturbed and mobilized cells. Chemotherapy
      related mobilization can be potentially dangerous in that severe myelosuppression
      necessary to achieve mobilization can have serious consequences. There are no
      controlled studies that evaluate the relative merits of each method of
      collection. Regardless of the techniques employed peripheral blood stem cells can
      reliably accelerate hematologic recovery after potentially myeloblative therapy
      and provide an alternative to bone marrow support.

PMID- 1363098
TI  - A rapid and sensitive method for HLA-DRB1 typing by acridinium-ester-labeled DNA
      probes.
AB  - A rapid and accurate detection of HLA class II antigen is essential for
      transplantation and for the understanding of disease susceptibility. Recent
      molecular genetic studies have revealed that the number of class II loci and the
      number of alleles at these loci are greater than had been previously detected. It
      is, therefore, of great importance to detect these extensive polymorphisms. A
      great deal of effort has been made on identification of individual HLA class II
      specificities at the DNA level, called "DNA typing." What seems to be lacking,
      however, is handling simplicity. Here we accomplished a simple method for HLA
      DRB1 typing based on hybridization of acridinium-ester (AE)-labeled DNA probes to
      amplified DNA. This method is called hybridization protection assay (HPA). By
      using 13 AE-labeled probes, 20 homozygous B-cell lines and leukocytes from 80
      healthy individuals were typed by HPA. The results were completely consistent
      with those obtained by polymerase chain reaction--restriction fragment length
      polymorphism. This method is suitable for mass screening because of its
      procedural simplicity and swiftness.

PMID- 1363100
TI  - Hematopoietic stem cell processing and cryopreservation.
AB  - Either bone marrow or peripheral blood may be harvested to provide hematopoietic
      stem cells (HSC) for autologous transplantation. Both, however, comprise
      heterogeneous cell populations. The HSC necessary for successful engraftment
      constitute a very small fraction of the cells harvested. After collection, the
      harvested cells usually undergo several processing steps to reduce the product
      volume, remove cells (such as mature blood cells or tumor cells), or to
      cryopreserve the cells for later reinfusion. Granulocytes and red blood cells,
      for example, survive cryopreservation poorly using freezing techniques designed
      for HSC. Therefore, bone marrows being cryopreserved must be depleted of mature
      blood cells to avoid toxicity from infusion of damaged mature blood cells. Mature
      blood cells may also impede the variety of tumor cell purging techniques
      currently being studied. These processings are designed to minimize the loss of
      HSC while achieving an appropriate HSC product for the individual patient. A
      number of apheresis devices and cell washers simplify the enrichment of HSC in
      the harvested cell products. In contrast, tumor cell purging techniques are not
      standardized between the various transplant centers.

PMID- 1363101
TI  - Tumor cell purging and positive selection of hematopoietic stem cells.

PMID- 1363102
TI  - Quality assurance and standards in hematopoietic progenitor processing.
AB  - Bone marrow transplantation is an increasingly important therapeutic procedure.
      As more laboratories have become involved in the processing of hematopoietic
      progenitor cells from marrow or blood, it has been recognized that standards are
      required for hematopoietic progenitor processing, storage, and handling. Quality
      assurance is the process of monitoring whether laboratory procedures, equipment,
      and personnel fulfill their expected functions, and the aim of quality assurance
      is to ensure compliance with standards. Some standards for hematopoietic
      progenitor processing have recently been issued by professional organizations.
      Although these standards are not comprehensive, where applicable they should be
      met or exceeded. In the absence of published standards, principles of good
      laboratory practice should guide quality assurance programs. This article
      presents concepts of quality assurance in hematopoietic progenitor processing,
      based on standard laboratory practice and published standards.

PMID- 1363103
TI  - Genetic and immunologic analysis of a family containing five patients with common
      variable immune deficiency or selective IgA deficiency.
AB  - A family with 13 members included 2 subjects with selective IgA deficiency (IgA
      D) and 3 subjects with common-variable immune deficiency (CVID), diseases which
      usually occur sporadically. Reciprocal combinations of B and T cells in vitro
      between one normal and two immune-deficient family members and normal subjects
      revealed that defective Ig synthesis was determined by the B cells, while the
      patient T cells functioned normally. Normal T helper and suppressor function was
      demonstrated even in one patient with CVID who developed a T-cell
      lymphoproliferative disorder associated with elevated IgM; this patient's B cells
      made only IgM in vitro. Immune deficiencies were inherited in this family in a
      pattern consistent with an autosomal dominant trait with incomplete penetrance.
      All the immune-deficient patients in this family possessed at least one copy of
      an MHC haplotype previously shown to be abnormally frequent in IgA-D and CVID:
      HLA-DQB1*0201, HLA-DR3, C4B-Sf, C4A-deleted, G11-15, Bf-0.4, C2-a, HSP70-7.5, TNF
      alpha-5, HLA-B8, and HLA-A1. The patient who developed the lymphoproliferative
      disorder was homozygous for this haplotype. Four immunologically normal members,
      one of whom was 80 years old, also possessed this MHC haplotype, indicating that
      its presence is not sufficient for disease expression. A small segment of another
      MHC haplotype associated with Ig deficiency in the population also occurred in
      this family, but it was not associated with immune deficiency.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1363104
TI  - Preferential expression and activity of multidrug resistance gene 1 product (P
      glycoprotein), a functionally active efflux pump, in human CD8+ T cells: a role
      in cytotoxic effector function.
AB  - The multidrug resistance gene 1 (mdr 1) product, the P-glycoprotein (Pgp), is a
      170-kD transmembrane transport protein, whose overexpression is associated with
      multidrug resistance in cancer cells and in chloroquine-resistant Plasmodium
      falciparum infection. In this study we show that normal freshly isolated human
      lymphocytes express low levels of mdr 1 mRNA and membrane Pgp. Although Pgp is
      expressed in both CD4+ and CD8+ T cells, it is preferentially expressed in CD8+ T
      cells. Activation of T lymphocytes with phytohemagglutinin leads to an
      amplification of both mdr 1 mRNA and membrane Pgp in T cells. P-glycoprotein in T
      cells is a functionally active efflux pump as demonstrated by decreased retention
      of rhodamine-123 and its increased accumulation by cyclosporin A, an inhibitor of
      Pgp function. In addition, MRK-16 antibody increased accumulation of Rh123 in
      CD8+ T cells. Furthermore, MRK16 anti-P-glycoprotein monoclonal antibody, in a
      concentration-dependent manner, inhibited T lymphocyte-mediated cytotoxicity.
      These data suggest a physiologic role of P-glycoprotein in cytotoxic T-lymphocyte
      effector function.

PMID- 1363105
TI  - 'Sterilization' of arthroscopes and laparoscopes.

PMID- 1363106
TI  - Endophthalmitis at the Bristol Eye Hospital: an 11-year review of 47 patients.
AB  - We reviewed data from 47 patients who were treated for endophthalmitis at our
      hospital during the 11-year period 1980-90. The most common clinical features
      were hypopyon (75%), diminished vision (72%), ocular pain (68%), discharge (57%),
      corneal oedema (51%), conjunctival injection (49%), abnormal red reflex (34%),
      corneal ulcer (32%) and corneal perforation (6%). A total of 54 isolates were
      obtained from 41 (87%) of the 47 patients. Gram-positive bacteria were more
      common (72%), than Gram-negative organisms (22%). Two cases were due to fungi,
      and herpes simplex virus was isolated from one case. The two most common Gram
      positive organisms were coagulase-negative staphylococci (25%), and
      Staphylococcus aureus (11%), while Pseudomonas aeruginosa predominated among the
      Gram-negative bacteria isolated (15%). Mixed bacterial species were obtained from
      29% of the infected patients, including one from whom Vibrio fluvialis was
      isolated. Predisposing factors included ocular surgery (60%)--mostly for cataract
      extraction (47%), penetrating trauma (15%) and periocular (15%) or systemic (11%)
      infections. All patients received antibiotics (generally chloramphenicol and/or a
      beta-lactamase-stable penicillin plus an aminoglycoside) prior to culture, when
      treatment was adjusted according to specific aetiological agents. Seventy-nine
      per cent of patients received topical or systemic steroids. Vitrectomy
      (diagnostic and therapeutic) was performed on 21% of patients. Sixty-three per
      cent of culture-positive patients lost vision (no perception of light) in the
      affected eye, compared to 17% of culture-negative cases (P < 0.05 Fisher exact
      test). Similarly, a better visual outcome (acuity of 6/12 or better) was
      associated with coagulase-negative staphylococcal infection than with
      streptococcal or fungal infections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363107
TI  - The mechanisms and risks of surgical glove perforation.
AB  - Intact surgical gloves are a barrier to hepatitis B virus and human
      immunodeficiency virus (HIV) but once perforated during surgery they cannot
      sustain adequate defence. This study examines the rate of glove perforations
      during surgery at a District General Hospital. In total, 275 pairs of gloves were
      collected from 100 consecutive operations. In the 43% of gloves that had been
      damaged 200 perforations were recorded. The mean rate per operation in the
      surgeon's gloves was 1.18. Injuries to the non-dominant index finger were
      significantly higher than injuries to other parts of the hand. Injuries occurred
      particularly during manipulation of the needles and at wound closure. Consultants
      were more likely to have glove perforation than juniors. Operations requiring
      manipulation of instruments deep within the wound had a higher rate than those on
      the surface. The results of the study indicate that a surgeon risks more than one
      hepatitis B infection per lifetime and that at least one in 1500 surgeons is
      likely to be infected by HIV during the next 35 years.

PMID- 1363108
TI  - Colonization with coagulase-negative staphylococci in two neonatal units.
AB  - Episodes of septicaemia due to coagulase-negative staphylococci (CNS) were more
      frequent in a level III than in a level II neonatal unit in Stockholm, Sweden.
      Colonization with CNS during the first 2 weeks of life was investigated in 10
      infants from each unit. As the use of antibiotics differed between the two units,
      the aim was to correlate colonization and antimicrobial resistance patterns to
      antibiotic usage. Antimicrobial susceptibility of CNS to isoxazolylpenicillins,
      co-trimoxazole, erythromycin, clindamycin, chloramphenicol and gentamicin was
      determined. Selected isolates were typed with restriction endonuclease analysis
      of plasmid DNA and of genomic DNA. Infants were frequently colonized with
      multiple strains and species of CNS, and transmission of strains from patient to
      patient occurred within the unit. Qualitative and quantitative differences in
      antibiotic use were not correlated with colonization. The prevalence of resistant
      isolates, mostly of Staphylococcus haemolyticus, was higher in the level II unit
      with lower use of antibiotics. Staphylococcus epidermidis, which is generally
      more virulent, prevailed in the level III unit, where there were more severely
      ill children and invasive procedures were more frequently performed.

PMID- 1363109
TI  - An outbreak of infection due to Staphylococcus aureus phage type 52 in a neonatal
      intensive care unit.
AB  - An outbreak of infection due to Staphylococcus aureus phage-type 52, resistant
      only to penicillin, occurred in children's wards primarily in a neonatal
      intensive care unit. The outbreak involved 86 infants; the majority presented
      with conjunctivitis, wound infections, boils, omphalitis and otitis externa.
      Seven per cent of these infants (six of 86) also had septicaemia. In addition, 6%
      (five of 86) were colonized by this phage type and the most common site of
      carriage was the umbilicus. The outbreak was contained by eradication of nasal
      carriage among the staff members and also by standard infection control measures.

PMID- 1363110
TI  - Bacteraemia caused by non-aeruginosa Pseudomonas species in a cancer centre.
AB  - Fifty-one episodes of bacteraemia due to Pseudomonas species other than
      Pseudomonas aeruginosa occurring between 1980 and 1990 in a Belgian cancer centre
      were reviewed. This corresponded to an incidence of 0.62/1000 admissions, or 1.5%
      of all bacteraemic episodes. Twenty-nine episodes, each with several positive
      blood culture sets were considered clinically significant, including six patients
      belonging to a well-documented outbreak of pseudobacteraemia with Xanthomonas
      maltophilia and associated with contaminated blood sampling tubes. The
      respiratory tract was the source in six (20.7%), an infected intravenous catheter
      in 10 (34.5%) and the source was unknown in seven (24.1%). Seven patients died
      from infection (24.1%). Twenty-three episodes with a single positive blood
      culture set were considered clinically not significant, although four of them
      were considered significant by the Centers for Disease Control (CDC) criteria
      because of the presence of symptoms and specific antibiotic treatment being
      administered. None of the patients with a single isolate died from infection
      despite the fact that 17 of 22 did not receive an effective antimicrobial agent.
      All isolates were susceptible to co-trimoxazole.

PMID- 1363111
TI  - Asymptomatic Salmonella senftenberg carriage in a neonatal ward.
AB  - During a 23-day period in April 1991, nine infants in a neonatal ward were found
      to be colonized with Salmonella senftenberg. All were asymptomatic on detection
      and all except one (who developed septic ileus) remained asymptomatic on follow
      up. The affected babies were isolated and subsequently discharged from the ward
      as soon as possible. These measures, along with emphasis on handwashing and
      intensification of cleaning and disinfection, were able to prevent spread to
      other babies. Despite extensive sampling of the environment, mothers and staff,
      the source of the organism could not be identified.

PMID- 1363112
TI  - Hospital infection control as a quality issue in the new management systems--is
      audit the answer?

PMID- 1363113
TI  - CAPD peritonitis caused by Lactobacillus rhamnosus.

PMID- 1363114
TI  - Outbreak of multiresistant pneumococci.

PMID- 1363115
TI  - Selective digestive tract decontamination and environmental gram-negative
      bacteria.

PMID- 1363116
TI  - Melioidosis and laboratory safety.

PMID- 1363118
TI  - Possible use of 1% Virkon solution for laboratory discard jars.

PMID- 1363117
TI  - Microbiological safety of outstationed laboratory equipment.

PMID- 1363119
TI  - Efficient and reproducible new semimicromethod for the detection and titration of
      HIV in human plasma.
AB  - A semimicromethod was established for isolating human immunodeficiency virus
      (HIV) in plasma using 48-well plates and a pool of peripheral blood mononuclear
      cells (PBMC) from several donors as targets for infection, which increases the
      efficiency of isolation by reducing the effect of variability due to diverse
      donor cell susceptibility to HIV infection. The addition of H9 cells to the PBMC
      cultures did not affect measurable titers. Nevertheless, it potentiated strongly
      virus replication in terms of p24 production in the supernatant of the wells with
      HIV isolates, thus facilitating interpretation of the results. The titration of a
      virus strain of a known titre and reverse transcriptase activity in parallel
      provided a constant parameter of efficiency and reproducibility within each
      experiment, permitting comparison with results from other laboratories. The
      reproducibility of the method was highly significant (r = 0.97, P < 0.001); 68%
      of the 22 plasma samples from HIV-infected individuals tested by this method were
      positive. The presence of plasma HIV titer correlated well (P < 0.02) with the
      low count of CD4+ cells of less than 300/mm3, but not with the presence of the
      p24 antigen in the serum.

PMID- 1363120
TI  - Increases in urinary enzyme excretion in rats depleted of glutathione inhibited
      by scavenger of oxygen free radicals.
AB  - Urinary excretion of enzymes by rats was assessed after glutathione (GSH) was
      depleted by treatment with a mixture of the GSH depletors D,L-buthionine-S,R
      sulfoximine (BSO) and diethylmaleate (DEM). Renal GSH was low 2 h after treatment
      and later returned to the control level. The urinary excretion of gamma
      glutamyltranspeptidase (gamma-GTP) and N-acetyl-beta-D-glucosaminidase (NAG)
      remained high for at least 3 d after the injection of BSO (100 mg/kg) and DEM
      (0.5 ml/kg), with no effect on the blood urea nitrogen level. N,N'
      Dimethylthiourea (DMTU), a scavenger of oxygen free radicals, inhibited this
      increase in the urinary excretion of gamma-GTP. DMTU also inhibited the increase
      in cisplatin-induced NAG excretion caused by the GSH depletors. These results
      suggested that the urinary excretion of these enzymes is an index of renal
      tubular injury caused by short-term depletion of renal GSH, and that the
      generation of free radicals may be involved in renal tubular injury during GSH
      depletion or caused by cisplatin together with GSH depletors.

PMID- 1363122
TI  - [Irritable bowel syndrome in adolescence].
AB  - We studied seventy patients, 23 males and 47 females with irritable bowel
      syndrome in adolescence aged 13-19 yrs, who visited the department of
      psychosomatic medicine in Takano Hospital during about six year period of April,
      1986-July, 1992. Takano Hospital is a coloproctological center in Kumamoto. In
      the clinical pattern of adolescent patients with irritable bowel syndrome the
      "gas" pattern was dominant (51.4%). Patients with the gas pattern have severe
      symptoms of flatus, fullness, rumbling sound and abdominal pain as well as bowel
      dysfunction, constipation and diarrhea in a classroom. Next, the diarrheal
      pattern occurred in 20.0%. Diarrheal patients complained of frequent bowel
      movements and retention feelings before attending school. Recurrent abdominal
      pain-like pattern was found in 7.1% patients. Clinical symptoms in the adolescent
      patients seem to derived from a mental tension and stress in a close classroom or
      before attending school. Many adolescenct patients (67.1%) with irritable bowel
      syndrome are embarrassed in school-maladjustment; leaving class early, late
      coming, a long absence, and a withdrawal.

PMID- 1363121
TI  - Nutrition and cancer: critical issues in basic science and clinical research.
      Proceedings of the 1992 ASPEN Research Workshop. Orlando, Florida, January 19,
      1992.

PMID- 1363123
TI  - [The general aspects of the treatment of irritable bowel syndrome].
AB  - Irritable bowel syndrome (I.B.S.) is treated with medication, change of life
      style, various psychotherapies, oriental medicine, and etc., But no specific
      therapy is recognized useful for all the symptoms derived from I.B.S.. In fact
      the combination of these therapies are useful. When the therapeutic schedule is
      planned for individuals, we must keep it in mind that the relief from the
      symptoms is most important for patients.

PMID- 1363124
TI  - [Pharmaceutical treatment of irritable bowel syndrome].
AB  - In the treatment of IBS best results could be obtained by implementing a
      comprehensive program for the patients. This might include a through examination,
      an explanation of the condition to the patients, psychologic managements, and
      correction of any bad habits, as well as drug therapy. The aim of drug therapy of
      IBS is the relief of the symptoms: such as abdominal pain, disturbed bowel
      function, anxiety or depression. As there is no drug which is effective in
      relieving the entire range of symptoms, drug should be chosen according to
      specific symptoms. Tranquilizers and antispasmodics may be the most commonly used
      drugs, however their efficacy is limited. To postprandial pain antispasmodics or
      trimebutine are most effective when prescribed before meal. Antidepressant are
      beneficial for the depressive state. Bulking agents are preferable mainly in
      relieving constipation, and loperamide is effective in treating diarrhea.

PMID- 1363125
TI  - [Synaptic plasticity and gene products].
AB  - Synaptic plasticity is thought to be the basic mechanism underlying learning and
      memory. The cellular mechanisms underlying synaptic plasticity have been
      extensively investigated in invertebrates and in vertebrates. What is the nature
      of synaptic plasticity? Can genes and gene products regulate plasticity? If so,
      how? The behavioral sensitization of the gill-and-siphon-withdrawal reflex of
      Aplysia is a simple model of plasticity in invertebrates, and can be examined in
      dissociated cell culture. Using a model of plasticity in cell culture, the
      molecular cascades of both short-term and long-term sensitization have been
      investigated, and characterized. Both gene transcription and protein synthesis
      were shown to contribute to the long-term sensitization. Long-term potentiation
      (LTP) is a well-characterized model for synaptic plasticity in vertebrates. Many
      possible cascades have been proposed, but it has not yet been settled whether an
      increase of transmitter release from presynaptic terminal, an increase of
      synaptic current, is responsible for the maintenance of LTP. Inhibition of
      protein synthesis resulted in a failure to maintain LTP over 3-4 hours. Thus, new
      protein synthesis may be needed for the maintenance of LTP. Induction of so
      called immediate early genes that are induced immediately upon depolarization or
      neurotransmitter stimulation of the neuron has been studied as a possible
      mechanism underlying LTP. However, there is no good evidence yet implicating gene
      regulation to be involved in plasticity in vertebrates.

PMID- 1363126
TI  - Identification and characterization of the alpha 2D-adrenoceptor subtype in
      single cells prepared from guinea pig tracheal smooth muscles.
AB  - Single cells were prepared from guinea pig tracheal smooth muscle and used in
      binding studies of [3H]p-aminoclonidine. Specific binding of [3H]p-aminoclonidine
      was saturable to a single class of receptors, with an equilibrium dissociation
      constant (KD) of 1.62 +/- 0.17 nM and a density (Bmax) of 6.20 +/- 0.78 x 10(4)
      sites/cell. Competition studies were carried out with several adrenergic
      antagonists. The rank order of potency was idazoxan = phentolamine > yohimbine >
      prazosin = corynanthine. These results suggest that the alpha 2-adrenoceptor in
      guinea pig tracheal smooth muscle represents a single pharmacological subtype,
      which is designated as alpha 2D.

PMID- 1363127
TI  - [Changes in the renin-angiotensin system and the effectiveness of the treatment
      of hypertension with calcium antagonists, beta-adrenoblockers and diuretics].
AB  - Renin response to nifedipine, verapamil, propranolol and hypothiazide was studied
      in 133 patients with Stage II hypertensive disease. The common mechanism of
      action in all these drugs was an increase in baseline plasma renin activity
      (PRA). In patients with a baseline high RPA, propranolol and nifedipine lowered
      it, whereas verapamil and hypothiazide unchanged it. Group analysis indicated
      that enhanced PRA during therapy was unassociated with diminished
      antihypertensive effects of an agent as compared with patients in whom RPA showed
      no increase. Propranolol was more effective in patients with high PRA than the
      other agents. The best nifedipine tolerance was recorded in patients with lower
      PRA.

PMID- 1363128
TI  - [Participation of opioids in the osmotically stimulated vasopressin secretion,
      Communication I. Methodological aspects of studying the problem (review
      lecture)].

PMID- 1363129
TI  - Nurse Education Tomorrow Conference 1992.

PMID- 1363130
TI  - A hyperpolarizing response induced by glutamate in mouse cerebellar Purkinje
      cells.
AB  - In the vertebrate nervous system, glutamate (Glu) receptors are generally known
      to cause depolarizing responses. We report here a novel type of Glu response in
      Purkinje neurons of mouse cerebellar slices, namely glutamate-induced
      hyperpolarization (GH). This response is not due to activation of inhibitory
      interneurons, because application of tetrodotoxin (TTX), bicuculline, or
      strychnine did not abolish GH. In addition, GH persisted in a Ca(2+)-free or a
      low-Cl- solution, which rules out the involvement of gK(Ca) or GABAA mechanisms.
      Quisqualate (Quis) and trans-1-amino-1,3-cyclopentanedicarboxylic acid (tACPD),
      which are potent and selective agonists, respectively, for the metabotropic Glu
      receptor (mGluR), failed to induce GH. L-2-Amino-4-phosphonobutyric acid (L-AP4)
      was also ineffective. Simultaneous recording of electrical activity and
      intracellular Ca2+ concentration ([Ca2+]i) showed that GH was not accompanied by
      [Ca2+]i changes. Voltage clamp experiments showed that GH is due to reduction of
      a tonically active conductance with a reversal potential around 0 mV. Two
      possible mechanisms are suggested for GH: (1) changes in the desensitized steady
      state of ionotropic Glu receptors, or (2) a novel Glu-mediated mechanism.

PMID- 1363131
TI  - The effect of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, in
      the forced swimming test.
AB  - The present study examined the effects of CGP 37849 and CGP 39551, competitive
      NMDA receptor antagonists, in the forced swimming test in rats and mice.
      Administered in a single dose or three times both examined compounds reduced the
      immobility time in rats. Active doses used in that test either did not change the
      locomotor activity or decreased it. A similar effect in both tests was shown by
      active (R)-enantiomers CGP 40116 and CGP 43487. Reduction of the immobility time
      induced by CGP 37849 and CGP 39551 in the forced swimming test in rats was
      antagonized by haloperidol and (+/-)-sulpiride, but not by SCH 23390 or prazosin.
      CGP 37849, but not CGP 39551, also reduced the immobility time in the forced
      swimming test in mice. The results obtained indicate that CGP 37849 and CGP 39551
      induce an antidepressant-like effect in the forced swimming test, probably via an
      indirect dopamine activation resulting from blockade of NMDA receptors.

PMID- 1363132
TI  - The effect of imipramine after single and repeated administration on the
      apomorphine response in the acoustic startle reflex in rats.
AB  - The paper presents the results of studies into the effects of single and repeated
      (2 or 10 mg/kg po, twice daily for 14 days) administration of imipramine (IMI) on
      the behavior of male Wistar rats in an acoustic startle response test.
      Statistically significant attenuation of the animal reactivity was observed after
      8 or 14 days administration of IMI in a dose of 10 mg/kg. Apomorphine APO (1.0
      mg/kg, ip) enhanced the animals reactivity after repeated (but not single)
      administration of IMI in a dose of 2 mg/kg. The obtained results confirm the
      hypothesis about an increase of the dopaminergic system reactivity under the
      influence of repeated administration of tricyclic antidepressants.

PMID- 1363133
TI  - Truffle melanogenesis: correlation with reproductive differentiation and ascocarp
      ripening.
AB  - The present work uses histochemical techniques to investigate the correlation
      between reproductive differentiation and age of truffles (Tuber aestivum and
      Tuber melanosporum) with melanin synthesis. The dopa oxidase and tyrosine
      hydroxylase activities of tyrosinase have been localized within the ascocarp and
      melanin localization was performed by the Schmorl's reaction. A true tyrosinase
      is present in truffles, able to oxidize both l-tyrosine and l-dopa. The
      tyrosinase activity is on in the young ascocarps (in the peridium, hypothecium,
      and fertile veins) and off in the ripe ones, thus it appears correlated with the
      age and differentiation of the sporogenic hyphae that arise from the hypothecium;
      a similar correlation has been previously described in Neurospora crassa, which
      is an ascomycete as well as the truffles.

PMID- 1363134
TI  - Intrinsic pigment-cell stimulating activity in the catfish integument.
AB  - In keeping with the concept that local factors in the vertebrate integument
      affect the expression of pigment cells, the present study was directed toward
      demonstrating the existence of such factors in the skin of the channel catfish,
      Ictalurus punctatus. This species has a dark dorsal surface in marked contrast to
      an almost white midventral surface. Pieces of skin from these two surfaces were
      used to condition culture media, which were in turn bioassayed using the Xenopus
      neural tube explant system (Fukuzawa and Ide, 1988, Dev. Biol. 129:25). A certain
      number of neural crest cells grow out from the explant, and many of these are
      melanized in a culture medium of Steinberg's basic salt solution (BSS). When the
      BSS was conditioned with either dorsal or ventral skin, a profound increase in
      both the number of crest cells emigrated from the neural tubes and the percentage
      of melanized cells was observed. The effects of dorsal skin were stronger than
      those of ventral skin and were evident on a dose/response basis. Initial
      fractionation of conditioned BSS with DEAE ion exchange chromatography produced
      fractions of particular potency in the stimulation of melanogenesis. A similarly
      conditioned medium based upon Leibovitz's L-15 was used in the primary culture of
      mature chromatophores, namely, melanophores, iridophores, and xanthophores from
      tadpoles of Rana pipiens. Both dorsal and ventral conditioned media stimulated
      iridophores and xanthophores, but seemed to have little or no effect on tadpole
      melanophores. A melanization inhibiting factor (MIF) from the ventral surface of
      adult frogs has been suggested as the basis for the light colored ventrum of
      amphibians, and although the present experiments were not designed to study
      catfish MIF, the possible existence of such a factor in this species was
      supported by the results. The total results of this investigation are discussed
      in the light of the possible presence of a melanization inhibiting factor (MIF)
      of greater prevalence in the ventrum and a melanization stimulatory factor (MSF)
      of greater prevalence in the dorsal integument. It is suggested that the light
      colored ventral surface of the catfish and other poikilotherms may result from
      the presence of higher levels of MIF than MSF. Thus, the expression of
      melanophores is inhibited while that of iridophores is enhanced. In contrast,
      higher levels of MSF over MIF in the dark dorsal surface would result in
      melanophore stimulation and inhibition of iridophore expression.

PMID- 1363135
TI  - Partial purification of a receptor for the adipokinetic hormones from Musca
      autumnalis face flies.
AB  - Partial purification of the receptors for the neurohormones, diptera corpora
      cardiaca factors 1 and 2 (DCC1 and DCC2) was achieved. Receptor proteins were
      obtained from the abdomens of face fly, Musca autumnalis De Geer. Purification
      methods included detergent solubilization, affinity chromatography, and
      polyacrylamide gel electrophoresis. Analysis by gel electrophoresis has
      identified two proteins from this partial purification with relative molecular
      weights of 45 and 90 kD. A crude receptor preparation was used to develop a
      ligand binding assay with radiolabeled (tritiated and iodinated) DCC1. Ligand
      binding was inhibited by 90% when excess unlabeled DCC1 was added to the assay
      mixture. Ligand binding was optimum at pH 7.5. Binding saturation occurred at
      approximately 12 picomole radiolabeled ligand concentration. Because DCC1 and
      DCC2 have been shown to effect the lipid and trehalose levels in the insect an
      understanding of the neuropeptide-receptor interaction is important for the
      development of new methods of control of dairy and poultry muscoid flies.

PMID- 1363136
TI  - Hormonal and neurochemical correlates of various forms of animal "aggression".
AB  - The majority of studies attempting to evaluate the roles of hormones and
      neurochemicals in "aggression" concern laboratory rodents, notably rats and mice,
      with fewer investigations on infrahuman primates. Studies suggest that situations
      used to assess aggression (e.g., social conflict tests, parental attack,
      predatory behavior, use of unavoidable electroshock) actually tap a diverse range
      of motivations whose functions include offense, defense and predation. It is also
      apparent that ethoexperimental techniques, i.e., those applying ethological
      methodologies and concepts to laboratory situations, have advantages in assessing
      the direct and indirect consequences of chemical treatments. In this review, the
      impacts of hormonal manipulation (by surgery and/or application) and varying
      neurotransmitters (studied in terms of regional changes and as consequences of
      drug treatments) on a variety of forms of behavior are assessed. Different tests
      do show varying responses to common treatments, confirming the heterogeneity of
      the available paradigms. A brief discussion is provided of which tests are likely
      to prove most relevant to clinical studies.

PMID- 1363138
TI  - Neuronal-Astrocytic Interactions. Implications for Normal and Pathological CNS
      function. Proceedings of a symposium. Hong Kong, July 10-13, 1991.

PMID- 1363137
TI  - Abnormal growth hormone and cortisol, but not thyroid-stimulating hormone,
      responses to an intravenous glucose tolerance test in normal-weight, bulimic
      women.
AB  - Abnormal growth hormone (GH) and adrenocorticotropic hormone (ACTH)/cortisol
      secretory patterns in response to a glucose load have been observed in
      underweight anorectic women. The present study was performed in an attempt to
      establish whether changes in the hypothalamic/pituitary sensitivity to
      hyperglycemia occur in bulimia in the absence of weight disturbance. Therefore,
      serum GH, plasma cortisol, and plasma insulin concentrations were measured in
      eight women with normal weight bulimia and in eight normal women during an
      intravenous glucose (0.33 g/kg as an IV bolus) tolerance test (IGTT). In
      addition, since abnormal pituitary hormone responses to a glucose load might
      reflect alterations in somatostatin (SRIH) release, TSH secretion also was
      measured, in view of its sensitivity to SRIH inhibition. Both GH and cortisol
      levels progressively and significantly declined during IGTT in the normal
      subjects. In the bulimic women, cortisol levels remained unchanged, whereas GH
      concentrations rose significantly after glucose injection. Plasma cortisol and
      serum GH levels were significantly higher in the bulimic than in the control
      subjects. No significant differences between groups were observed in
      hyperglycemia-induced insulin increments or in TSH decrements. These data
      indicate that an altered sensitivity to hyperglycemia affects the
      hypothalamic/pituitary centers controlling the secretion of the counterregulatory
      hormones GH and ACTH/cortisol in bulimia nervosa. The lack of a simultaneous
      change in the TSH secretory pattern argues against a possible involvement of SRIH
      in the pathophysiology of this disorder.

PMID- 1363139
TI  - Early response gene induction in astrocytes as a mechanism for encoding and
      integrating neuronal signals.
AB  - Astrocytes in vitro readily respond to a wide variety of neuronal and systemic
      signals by inducing a complex pattern of early response genes (ERGs). The level
      of complexity is evident in both the ligand-associated expression kinetics and
      levels of message accumulation as well as in the heterogeneity of response within
      a population of astrocytes. Ligand-restricted expression of ERG mRNAs suggest
      that all astrocytes in culture are not alike. Although the ability of glial cells
      to express ERGs appears to be highly restricted in vivo, one important exception
      is the category of glial response to injury. Long-term expression of multiple ERG
      proteins in glial cells stimulated by neuropathological conditions may play an
      important role in the outcome of brain injury and neurodegenerative disease. The
      extensive and staggered expression of ERG proteins acting as transcription
      factors may represent a mechanism for temporally coordinating the genomic program
      of large sets of genes associated with glial cell response to neuronal
      dysfunction. As part of the neuronal-glial interdependency, glial ERG expression
      may encode and integrate the environmental signals associated with neuronal
      damage and promote the proper restoration of neuronal function. For example,
      ligand-induced ERG expression regulates the transcription of the nerve growth
      factor (NGF) gene in glia which could have important functional consequences on
      neuronal survival and process outgrowth. Future studies will clarify the
      mechanisms that lead to the expression of ERGs and the subsequent complex,
      temporally ordered combinatorial consequence of numerous ERG proteins acting as
      transcription factors impinging upon target gene promoters. Such studies will
      enrich our understanding of astrocyte-neuronal interaction, clarify how distinct
      sets of genes in glial cells contribute to the problem and/or solution of
      neuropathological situations and guide our efforts to diagnose and treat
      neuropathological conditions.

PMID- 1363140
TI  - Regulatory role of astrocytes for neuronal biosynthesis and homeostasis of
      glutamate and GABA.

PMID- 1363141
TI  - Nitrogen metabolism: neuronal-astroglial relationships.

PMID- 1363142
TI  - Ultrastructural immunocytochemical observations on the localization, metabolism
      and transport of glutamate in normal and ischemic brain tissue.

PMID- 1363143
TI  - Release of exogenous and endogenous neurotransmitter amino acids from cultured
      astrocytes.

PMID- 1363144
TI  - Glutamate as an energy substrate for neuronal-astrocytic interactions.

PMID- 1363145
TI  - Kainic acid-induced excitotoxicity in neurons and glial cells.

PMID- 1363146
TI  - An in vitro study on increased neuronal and astrocytic vulnerability to
      neurotoxic injury after in utero cocaine exposure: the reversal effects of GM1
      treatment.

PMID- 1363147
TI  - Influence of the neuronal environment on the pattern of reactive astrocytosis
      following cerebral ischemia.

PMID- 1363148
TI  - PrPSc causes nerve cell death and stimulates astrocyte proliferation: a paradox.

PMID- 1363149
TI  - Swelling of C6 glioma cells and astrocytes from glutamate, high K+ concentrations
      or acidosis.

PMID- 1363151
TI  - Structure an interactions of molecules of the immune system. European Network of
      Immunology Institutes Conference. May 20-24, 1992. Abstracts.

PMID- 1363150
TI  - [Therapeutic use of somatostatin analogues in endocrinology].
AB  - The recent availability of the long-acting somatostatin analogue, octreotide, has
      allowed its therapeutical use in a wide variety of human diseases, including some
      digestive, neoplastic and autoimmune disorders. This review focuses on the
      treatment of some endocrine disorders with octreotide. Evidence is accumulating
      that octreotide treatment is effective in improving the cure rate of pituitary
      surgery in acromegaly by shrinking the tumour size, and in lowering GH and IGF-I
      levels in the vaste majority of patients. Octreotide is also effective in
      ameliorating TSH-induced hyperthyroidism in patients with TSH-secreting adenomas.
      Moreover, octreotide has proved useful in the management of endocrine tumours of
      the gastroenteropancreatic tract (vipomas, glucagonomas, gastrinomas,
      insulinomas, and carcinoids) by reducing hormone levels and in some instances the
      size of the primary and/or metastatic lesions. Besides the above well-established
      indications there are some other potential indications (non-secreting pituitary
      tumours, medullary thyroid carcinoma, ectopic Cushing's syndrome, diabete
      mellitus, Graves' ophthalmopathy, tall children and polycystic ovary syndrome)
      that still await further investigation. Side-effects of octreotide, particularly
      the formation of gallstones, should be carefully monitored.

PMID- 1363153
TI  - Broken wire repair.

PMID- 1363152
TI  - [Treatments of multiple myeloma in 1992].
AB  - In 1992, the Melphalan-Prednisone (M. P.) protocol remains a standard treatment
      of multiple myeloma even if a lot of new ways have been investigated during the
      last years. Polychemotherapies may appear better than M.P. for high tumor mass
      myeloma. Interferon is useful as maintenance treatment after chemotherapy.
      Combinations of interferon and chemotherapy, during the induction phase, are
      under evaluation. Because of their toxicity, heavier treatments, with stem cells
      reinfusion, are being developed mainly with younger patients. Thanks to these
      approaches the response's rate is increasing but any improvement of survival is
      still to be demonstrated. Other recent investigations have concerned
      diphosphonates and immunoregulators. Larger use of these new treatments requires
      more informations about prognostic factors and their integration in therapeutic
      strategy of myeloma.

PMID- 1363154
TI  - Respiratory burst of neutrophils enhances in hemorrhagic fever with renal
      syndrome (HFRS).
AB  - Respiratory burst of neutrophils was studied in 40 serologically verified
      patients with hemorrhagic fever with renal syndrome (HFRS) using luminol
      dependent chemiluminescence (CL). Markedly increased CL has been demonstrated
      since the first days of the illness in all investigated patients. The level of CL
      was much enhanced during initial, oliguric, polyuric stages and convalescence. In
      a case of HFRS complicated by shock CL was approximately 100-fold higher than in
      healthy controls. It is suggested that neutrophils have an important role in the
      pathogenesis of HFRS.

PMID- 1363155
TI  - Propionate metabolism in cultured human cells after overexpression of recombinant
      methylmalonyl CoA mutase: implications for somatic gene therapy.
AB  - Strategies for somatic gene therapy must consider the metabolic consequences of
      expressing the recombinant gene product in addition to methods for gene transfer
      and expression. We describe studies of propionate metabolism in cultured cells
      transfected with methylmalonyl CoA mutase (MCM), the enzyme deficient in mut
      methylmalonic acidemia. Transfection of MCM into mut fibroblasts restores
      propionate metabolism to normal levels in a dose-dependent manner. Overexpression
      of MCM, or the addition of excess propionate, carnitine, or cobalamin, does not
      increase propionate metabolism in normal human fibroblasts, lymphoblasts, or
      hepatoma cells, although hepatic cells exhibit > 10-fold higher levels of
      propionate metabolism. Significantly, the restoration of propionate metabolism in
      mut fibroblasts is disproportionately greater than the efficiency of
      transfection, suggesting the presence of a cooperative phenomenon between cells.
      Intercellular participation in propionate metabolism is evident in cocultures of
      MCM-deficient and propionyl CoA carboxylase-deficient cells. We conclude that the
      liver is the preferred target for gene therapy of MCM deficiency because of its
      greater capacity for propionate metabolism and that cooperation between cells
      could enhance the biological effect of a subpopulation of cells transformed with
      recombinant MCM.

PMID- 1363156
TI  - Correction of methylmalonyl-CoA mutase deficiency in Mut0 fibroblasts and
      constitution of gene expression in primary human hepatocytes by retroviral
      mediated gene transfer.
AB  - Methylmalonic acidemia is an often fatal inborn error of organic acid metabolism
      due to deficiency of methylmalonyl-CoA mutase. The cloning of genes encoding this
      enzyme and the advent of technologies for gene transfer have introduced the
      possibility of somatic gene therapy for this disorder. Gene therapy may require
      replacement of the defective enzyme in hepatocytes, which have a greater capacity
      for propionate metabolism than other somatic cells and represent the principle
      physiological site of propionate metabolism. We describe construction of an
      amphotropic retroviral vector containing the human methylmalonyl-CoA mutase cDNA.
      This vector is shown to transduce primary MCM-deficient fibroblasts and restore
      levels of [14C]propionate metabolism by cultures of nonselected cells to normal.
      This vector will transduce primary human hepatocytes and direct transcription of
      recombinant human MCM from the integrated provirus. This work demonstrates the
      feasibility of retroviral-mediated gene transfer of methylmalonyl-CoA mutase into
      primary human cells, including hepatocytes which represent a difficult, but
      potentially necessary, target for gene therapy of methylmalonic acidemia.

PMID- 1363158
TI  - Tumor formation and sister chromatid exchange induction by ethyl carbamate:
      relationships among non-pregnant murine females, gravid dams, and
      transplacentally exposed offspring.
AB  - Sister-chromatid exchange (SCE) induction and cell cycle kinetics alterations by
      ethyl carbamate in bone marrow of non-gravid murine Swiss Webster, ICR/Jcl, and
      C57Bl/6J dams were evaluated, and data from non-gravid females were compared with
      those previously reported for pregnant dams of the same strains. In addition,
      lung adenoma induction by ethyl carbamate in gravid Swiss Webster dams, their
      offspring, and in non-pregnant Swiss Webster females was also determined.
      Relative cytogenetic and tumor responses in non-gravid and gravid Swiss Webster
      females and their offspring were compared. In contrast to the increased
      sensitivity reported for gravid Swiss Webster dams versus ICR/Jcl and C57Bl/6J
      dams, SCE responses to 1.1, 2.2, or 3.3 mmol/kg of ethyl carbamate in non-gravid
      females were approximately equivalent among strains. In Swiss Webster and
      C57Bl/6J (but not ICR/Jcl) strains, SCE responses in non-gravid females at 2.2
      and 3.3 were significantly lower than those of their pregnant counterparts. Tumor
      induction by 3.3 mmol/kg ethyl carbamate paralleled relative SCE induction with
      Swiss Webster dams, demonstrating a 5-fold increase in the number of tumors
      relative to their offspring and a 4-fold enhancement of tumor induction relative
      to their non-pregnant counterparts.

PMID- 1363157
TI  - Identification of kinetochores and DNA synthesis in micronuclei induced by
      mitomycin C and colchicine in Chinese hamster ovary cells.
AB  - The presence of kinetochore and DNA synthesis in micronuclei (MN) induced in
      Chinese hamster ovary (CHO) cells by clastogenic and aneuploidogenic substances
      such as mitomycin C (MMC) and colchicine was determined by immunofluorescence
      technique using CREST antikinetochore antibodies and anti-bromodeoxyuridine
      (BrdUrd) antibodies. A cytofluorimetric analysis was also performed. Colchicine
      significantly increased micronucleated cells at least up to 96 h from the end of
      treatment. As expected, among colchicine-induced micronucleated cells the
      majority contained at least one CREST + MN. MMC induced a significant increase in
      micronucleated cells up to 120 h from the end of treatment and the great majority
      of MN lacked kinetochore fluorescence, indicating that MMC-induced MN were
      derived from acentric fragments. However, colchicine and MMC at 48 and 72 h from
      the end of treatment, induced a significant increase of CREST- and CREST + MN,
      respectively, suggesting an induction of clastogenicity by colchicine and
      aneuploidy by MMC. The clastogenic effect of colchicine after 48 h was also
      confirmed by the presence of chromatid fragments in metaphase cells. A
      cytofluorimetric analysis indicated that, as expected, colchicine and MMC
      interfere with the G2/M and S phases, respectively; however, a slight
      interference of colchicine with the S phase was also observed. DNA synthesis was
      present in MN and it was in most cases synchronous with synthesis in the main
      nucleus. The frequency of cells with MN in S phase observed in untreated or MMC
      treated cells is in agreement with the proportion of cells without MN showing DNA
      synthesis. On the contrary, the frequency of cells with MN in S phase observed in
      colchicine-treated cells was significantly lower than that observed in control
      and MMC-treated cells.

PMID- 1363159
TI  - Effects of various bile acids and their sodium salts on development of pepsinogen
      altered pyloric glands in rats.
AB  - Effects of dietary bile acids and their sodium salts on the development of
      pepsinogen-altered pyloric glands (PAPG) were examined in male WKY/N Crj rats
      initially given a single dose of 160 mg/kg body weight of N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) by gastric intubation. From week 3 the animals were
      administered basal diet containing 0.5% supplements of cholic acid (CA),
      deoxycholic acid (DCA), chenodeoxycholic acid (CDCA) or their sodium salts (Na-C,
      Na-DC and Na-CDC), or 5% ascorbic acid (ASA) or its salt (Na-AS) for 18 weeks.
      The concentration of DCA and Na-DC was reduced to 0.3% from week 12. At week 20,
      animals were killed and the numbers of immunohistochemically-demonstrated PAPG
      were determined. Values were significantly higher with Na-C and Na-CDC than with
      the corresponding parent acids, and in the Na-C case PAPG development was greater
      than with MNNG alone. In addition, Na-CDC itself induced the numbers of PAPG
      significantly. These results suggest that bile salts are possible intrinsic
      promoters of gastric carcinogenesis. They were without effect, however, on
      forestomach lesions.

PMID- 1363160
TI  - The modulatory effects of tryptamine and tyramine on the S9-mediated mutagenesis
      of IQ and MeIQ in Salmonella strain TA98.
AB  - The S9-mediated mutagenesis of IQ and MeIQ in Salmonella strain TA98 was
      modulated by introduction to the assay of tryptamine or tyramine. Both biogenic
      amines inhibited or enhanced the mutagenic response as a function of amine
      concentration, strain of rat used as the S9 source, and the IQ-type mutagen
      tested. Enhancement of IQ mutagenesis by tryptamine (10-80 microM) was observed
      in the presence of S9 preparations derived from Aroclor 1254-pretreated Fischer
      rats; the enhancing effect ceased at tryptamine concentrations > 160 microM. When
      Sprague-Dawley-S9 or Wistar-S9 were used for activation, the enhancement of IQ
      mutagenesis by tryptamine shifted to inhibition at tryptamine concentrations > 40
      microM, with Sprague-Dawley-S9, and > 20 microM, with Wistar-S9. By contrast,
      MeIQ-mutagenesis was enhanced by tryptamine (10-160 microM), regardless of the
      rat strain used as S9 source. Tyramine was a weaker enhancer of MeIQ mutagenesis
      than was tryptamine and, unlike tryptamine, its inhibitory effects on IQ
      mutagenesis were observed only with Wistar-S9. Tryptamine (10-80 microM)
      inhibited cytochromes P450IA1 and P450IA2 activities, monitored by the O
      deethylation of ethoxyresorufin and Glu-P-1 mutagenesis in TA98, respectively.
      These data suggest that the effects of biogenic amines on IQ and MeIQ
      bioactivation are complex. Furthermore, this study demonstrates that tryptamine
      and tyramine act both as enhancers (comutagens) and as inhibitors (antimutagens)
      of IQ and MeIQ mutagenesis, depending on the testing conditions.

PMID- 1363161
TI  - Task force proposes nurse prescribing, sends report to governor.

PMID- 1363162
TI  - Why aren't there more physician 'extenders'?

PMID- 1363163
TI  - The prevalence of arboviral, rickettsial, and Hantaan-like viral antibody among
      schoolchildren in the Nile river delta of Egypt.
AB  - A serosurvey was conducted during October and November 1989 to estimate the
      prevalence of selected arboviral, rickettsial, and Hantaan viral antibody among a
      sample of schoolchildren from 4 villages in the Bilbeis area of the Nile river
      delta, Egypt. Blood specimens were obtained from subjects aged 8 to 14 years.
      Enzyme immunoassay testing of the sera indicated that the prevalence of antibody
      was 9% (21/223) for Sicilian sandfly fever, 4% (8/223) for Rift Valley fever, 3%
      (15/437) for West Nile virus and 9% (28/315) for Hantaan (HTN) virus. Antibody
      was demonstrated among 22% (93/418) of the same study subjects against Coxiella
      burnetti, 53% (199/373) against Rickettsia typhi, and 37% (137/371) against R.
      conorii.

PMID- 1363164
TI  - The influence of low protein diet on the testicular toxicity of di(2
      ethylhexyl)phthalate.
AB  - Oral administration of di(2-ethylhexyl)phthalate (DEHP) at 1000 mg/kg body weight
      to adult male albino rats maintained on low protein (LP) diet for 15 d resulted
      in a greater decrease in absolute and relative weights of the testis and in
      epididymal sperm count than in those rats maintained on a normal protein (NP)
      diet. A marked increase in the activity of testicular beta-glucuronidase and
      gamma-glutamyl transpeptidase (GGT) in the LP-fed animals suggested that LP diet
      enhanced the vulnerability of Sertoli cells towards DEHP. A greater decrease in
      the activity of testicular acid phosphatase, lactate dehydrogenase isoenzyme-X
      (LDH-X) and sorbitol dehydrogenase (SDH) in the LP-fed animals occurred in
      comparison to NP-fed animals. Degeneration of mature germinal cells in the LP-fed
      animals on exposure to DEHP suggested that LP diets enhance the susceptibility of
      the testis towards DEHP.

PMID- 1363165
TI  - The relationship between anti-human eye muscle antibodies and thyroid function,
      anti-TSH receptor antibodies and eye symptoms in Graves' ophthalmopathy.
AB  - Circulating IgG, IgA, and IgM antibodies to human eye muscle cytosol antigens
      were studied in 60 patients with Graves' ophthalmopathy using the indirect ELISA
      method. There was a significant difference in the levels of both IgG and IgA
      antibodies between the patients with Graves' ophthalmopathy and a control group
      (p < 0.001). IgA antibodies to eye muscle cytosol antigens were raised in 20 out
      of 29 patients with proptosis (class 3 ophthalmopathy), in comparison with 31
      patients out of the total group of 60 with Graves' ophthalmopathy (p < 0.02).
      Anti-TSH receptor antibodies (TRAK) were not present in over half of the 31
      patients with raised IgA antibodies to eye muscle antigens. However, a
      significant difference was found between the levels of IgG and IgA antibodies in
      the TRAK-negative patients (p < 0.05). These findings suggests that both IgG and
      IgA antibodies to eye muscle antigens might be important in the development of
      ophthalmopathy.

PMID- 1363166
TI  - [Currents aspects of H2 receptor antagonists in the treatment of ulcers].
AB  - Inhibition of H2 receptors has been the first fully evaluated treatment of peptic
      ulcer and remains the most widely used mode of therapy. In this review, we
      summarize the current data on clinical pharmacology, therapeutic indications and
      results of the four currently used drugs: cimetidine - ranitidine - pepticidine -
      nizatidine. Their similarities are stressed. Recent data are underlined. The
      superiority or necessity of a single evening dose is questioned, as well as the
      clinical importance of tolerance and rebound. The effect on gastric alcohol
      dehydrogenase is mentioned pending further work on the clinical importance of
      this discovery. In the acute treatment, the antisecretory potency is of major
      importance in duodenal ulcer, the duration of treatment in gastric ulcer.
      Maintenance treatment prevents complication as well as recurrence. H2 receptor
      antagonists remain a primary treatment of peptic ulcer.

PMID- 1363167
TI  - [Therapeutic efficacy of 5-ASA molecules in idiopathic intestinal inflammatory
      diseases: critical review].
AB  - Sulfasalazine has been the most widely prescribed drug for patients with
      inflammatory bowel disease. Clinical trials have established its usefulness in
      treating patients with active ulcerative colitis and Crohn colitis and its
      important role in maintaining remissions in patients with ulcerative colitis.
      Despite its widespread acceptance, the usefulness of sulfasalazine has been
      limited by the occurrence of adverse reactions in about 10 to 20% of the
      patients. Now the aminosalicylates are emerging as a treatment for both
      ulcerative colitis and Crohn disease. We have critically reviewed the clinical
      trials assessing the efficacy of 5-ASA molecules. Therapeutic efficacy of 5-ASA
      appears to be as good as sulfasalazine but causing less adverse effects. In mild
      to moderate ulcerative colitis relapse, 2g 5-ASA is active while 1 g 5-ASA seems
      equivalent to 2g sulfasalazine for maintaining remission. 5-ASA enema in the
      treatment of distal ulcerative colitis is helpful and can replace topical
      cortisone administration. Administration of 1g 5-ASA enema a day seems to be the
      best regimen. In case of Crohn's disease, preliminary studies are encouraging but
      more date are required to define the indications as well as the regimen.

PMID- 1363168
TI  - Light and electron microscopic immunocytochemical localization of glutamine
      synthetase in the superficial pineal gland of the rat.
AB  - Glutamine synthetase (L-glutamate:ammonia ligase; EC 6.3.1.2), an enzyme
      catalysing the ATP-dependent formation of glutamine from glutamate and ammonia,
      was detected immunocytochemically only in glial (interstitial) cells of the
      superficial pineal gland of the rat. The results show the important role of
      pineal glial cells in the metabolism of the presumptive neurotransmitters,
      glutamate and gamma-aminobutyric acid (GABA) as well as in detoxification of
      ammonia.

PMID- 1363169
TI  - Radioimmunoassay for a new phenothiazine derivative and its application.
AB  - Fluphenazine-4-chlorophenoxy-isobutyrate ester, a new phenothiazine derivative
      was synthesized in the Institute for Drug Research Budapest. Radioimmunoassay was
      developed for the therapeutic monitoring of the drug level after intramuscular
      depot injection. The fluphenazine hapten was coupled to BSA by mixed-anhydride
      method. Antisera were produced to this conjugation in New-Zealand white rabbits
      and were tested for the antibody-titer. The specificity was tested by the cross
      reaction with phenothiazine-analogues and other psychotropics. Strong cross
      reaction was found with compounds possessing piperazine in side chain
      (trifluoperazine, perphenazine), but other psychotropic drugs did not react.
      Tritium-labelled trifluoperazine (spec. activity: 3.5 TBq/mmol) was used as a
      tracer in the radioimmunoassay. The detection limit was 75 pg with a CV of < 5%
      in 50 microliters plasma sample (equivalent to 1.5 ng/ml concentration) and a
      standard curve in the 3 ng/ml-50 ng/ml GYKI-22441 concentration range showed a CV
      of < 10%. Preliminary pharmacokinetic study was performed in Beagle dogs after
      intramuscular depot injection with GYKI-22441 in sesame oil in a dose of 0.1
      mg/kg. The GYKI-22441 concentration of the plasma samples were measured by the
      RIA method during a 28-day interval after the treatment and was evaluated by the
      MultiCalc Immunoassay Data Management program (Pharmacia).

PMID- 1363172
TI  - Oxygen Transport to Tissue XIII. Proceedings of the 18th annual meeting of the
      ISOTT. Townsville, Queensland, Australia, July 19-22, 1990.

PMID- 1363170
TI  - Development of phenylethanolamine N-methyltransferase (PNMT) in cultures of
      dissociated embryonic rat medulla oblongata.
AB  - The adrenergic phenotypic marker, phenylethanolamine N-methyltransferase (PNMT)
      is expressed in a subgroup of catecholaminergic neurons in the brain, as well as
      in the chromaffin cells of the adrenal medulla. Although PNMT in the rat adrenal
      is regulated by glucocorticoids, PNMT in the rat brainstem appears not to be
      regulated by glucocorticoids. Furthermore, little is known about factors required
      for the differentiation of this specific class of central neuron. The
      identification of such factors has been hampered not only by the heterogeneity of
      cell types in the brainstem, of which only a smaller number express PNMT, but
      also by the lack of a well characterized in vitro system in which the development
      of these neurons can be studied under defined conditions. The present study
      addresses this issue by establishing and characterizing a culture system for the
      study of adrenergic neurons. Dissociated cultures were prepared from embryonic
      rat medulla oblongata and the expression and development of PNMT was studied
      using immunocytochemistry and radioisotopic assay of PNMT activity. The survival
      of PNMT-immunoreactive (IR) neurons in vitro was found to be critically dependent
      on embryonic age. Numerous PNMT-IR neurons were observed in cultures prepared
      only from embryos of 46-51 somites (embryonic day E13-13.5). In contrast,
      cultures containing numerous neurons immunoreactive for tyrosine hydroxylase
      (TH), the rate-limiting enzyme in catecholamine biosynthesis, could be
      successfully established from medulla oblongata of any age between E13 and
      E16.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363173
TI  - The truncated TCA cycle in HeLa cell mitochondria.

PMID- 1363171
TI  - Neuron-enriched cultures derived from spinal cord of 10-day-old chick embryos:
      influence of neuropeptides on neuronal survival, proliferation and cholinergic
      expression.
AB  - The developmental regulation of cell proliferation, survival and cholinergic
      expression by growth hormone-releasing hormone (GHRH) and somatostatin (SRIF) was
      investigated in neuron-enriched cultures derived from 10-day-old embryonic chick
      spinal cord. In this study, 3H-thymidine in corporation into DNA was assessed,
      using two different applications, in order to determine both cellular
      proliferation and survival. The rate of neuroblast proliferation in both control
      and neuropeptide-treated cultures increased or remained the same up to day 6.
      However, in neuropeptide-treated cultures the magnitude of cell proliferation
      remained at levels higher than those observed in controls through day 6 and was
      most significant in SRIF-treated cultures at C4. In all groups, proliferation
      markedly declined by day 8. Survival of neuronal cells labelled at C4 remained
      high up to day 12 in all three groups, then drastically declined by day 17.
      Neuronal survival in the neuropeptide-treated cultures was also higher than in
      controls. Cholinergic expression, as assessed by activity of choline
      acetyltransferase (ChAT), responded differentially to neuropeptide treatment.
      Cultures treated with GHRH (100 nM) exhibited a long term significant enhancement
      in ChAT activity throughout the culture period, whereas those treated with SRIF
      (50 nM) expressed a transient decline in ChAT activity. Videometric analysis
      showed that both neuropeptides enhanced neuronal aggregation, neuritic
      arborization and neuritic length. These findings lead us to suggest that GHRH and
      SRIF may provide neurotrophic signals important not only for neuronal
      proliferation and survival but also for cholinergic neuronal expression.
      Furthermore, we propose that GHRH possesses specific cholinotrophic properties,
      whereas SRIF may act as a general neurotrophic factor.

PMID- 1363174
TI  - A comparison of parameters used to standardize results from in vitro perfusions
      of human placentae.

PMID- 1363175
TI  - Montenegro skin tests for American cutaneous leishmaniasis carried out on school
      children in Rio de Janeiro, Brazil: an indicator of transmission risk.
AB  - Montenegro skin tests were carried out in 1985 and 1987 on two groups of school
      children in the city of Rio de Janeiro. Group A consisted of 449 children
      residing in the Jacarepagua district, in areas where transmission of human and
      canine American cutaneous leishmaniasis (ACL) has been high; this group was
      considered to be the one at greatest risk of acquiring the infection through L.
      braziliensis. Group B consisted of 282 children from Bonsucesso, a suburb of Rio
      de Janeiro that is at a considerable distance from any area where ACL is endemic;
      this was a lowest risk group, and was thus used as a control. Analysis of the
      cutaneous test results showed that in Group A, 8.9% of the sample tested
      positive, whereas in Group B the result was only 2.1%. In group A there were no
      significant differences in the proportion of positives when analysed according to
      sex, age and the year when the tests were carried out. A study of the effects
      associated with place of residence together with other variables was carried out
      using log-linear regression analysis. It showed that effects arising from place
      of residence were maintained; that this was the only significant effect; and that
      it was independent of other variables. The testing of school children using the
      Montenegro intradermal test was shown to be a useful procedure in the
      characterization of localities in which there is a risk of ACL infection.

PMID- 1363176
TI  - The efficacy of ethion EC (1010 g/l) against cattle ticks in Morogoro, Tanzania.
AB  - Ethion, an organophosphorus insecticide/acaricide, was found to be effective
      against the various cattle ticks present in Morogoro Tanzania after it was
      sprayed on cattle twice weekly for 1 year. The pre- and post-replenishment
      concentrations of ethion ranged between 0.04 and 0.05%. Ethion was found to be
      stable in the spraywash. The good efficacy makes ethion a good alternative to
      dioxathion in tick control in Tanzania.

PMID- 1363177
TI  - Fibrinolytic activity in women on oral contraceptive pills: variation due to
      haemoglobin genotype.
AB  - Plasma fibrinogen levels and euglobulin lysis time (ELT) were determined in 84
      women with haemoglobin genotype AA (HbAA) and in 38 with haemoglobin genotype AS
      (HbAS), aged 17-35 years, who were on oral contraceptive pills (OCP). The control
      group included 23 HbAA and 27 HbAS age-matched, apparently healthy women, who had
      regular menstruation and no history of OCP usage. The controls showed
      statistically significant elevations in fibrinogen levels in women with genotype
      HbAS (+13%; P < 0.05) compared with women with genotype HbAA. Among OCP users,
      the difference in fibrinogen levels (+5%) between HbAS and HbAA women was not
      statistically significant. The elevation in fibrinogen levels which was
      restricted to the HbAA women, was probably caused by OCP use, and may be
      dependent on the Hb genotype. In contrast, the observed elevations in euglobulin
      lysis time among OCP users (P < 0.005) were independent of Hb genotype. Thus,
      while OCP may constitute a risk factor for the development of thromboembolism in
      women, the S-gene may confer partial protection against this development in women
      who have the HbAS genotype.

PMID- 1363178
TI  - Antibody patterns in rabbits showing different levels of susceptibility to an
      experimental Trypanosoma evansi infection.
AB  - Using SDS-PAGE and Western blotting, the antibody spectrum of rabbits infected
      with Trypanosoma evansi to homologous T. evansi antigens was monitored. Animals
      that developed parasitaemia later or had lower levels of parasitaemia as the
      infection progressed were considered to have a degree of resistance to the
      infection. Sera of these resistant animals recognised the T. evansi antigens
      earlier and subsequently identified more antigens than their susceptible
      counterparts. The susceptible animals developed patent parasitaemia earlier and
      had higher parasite counts as the infection progressed, and their sera recognised
      T. evansi antigens later with fewer parasite components labelled during the
      course of the infection. These observations demonstrate clear differences between
      animals in response to T. evansi infections. Selection of T. evansi-tolerant
      animals on an individual basis may be possible as has been suggested for other
      trypanosome species.

PMID- 1363179
TI  - Non-involvement of nulliparous females in the transmission of bancroftian
      filariasis.
AB  - The possible involvement of nulliparous females of Culex quinquefasciatus in the
      transmission of bancroftian filariasis under field conditions was examined in
      Pondicherry, South India. Biting nulliparous females that had previously ingested
      partial blood meals were found infected with microfilariae/L1 stage larvae. None
      of them harboured infective-stage larvae. These findings suggest that nulliparous
      females are not involved in the transmission of filariasis. Therefore, their
      inclusion for estimating the transmission parameters is questionable. However,
      nulliparous females should also be dissected in order to determine the vector
      infection rates accurately. Infective larvae were encountered in females of all
      other age groups.

PMID- 1363180
TI  - Control of mosquito larvae in the port city of Assab by an indigenous larvivorous
      fish, Aphanius dispar.
AB  - A randomized controlled trial was carried out in Assab under the auspices of the
      National Organization for the Control of Malaria and other Vectorborne Diseases
      of Ethiopia to assess the effectiveness of an indigenous cyprinodontid fish,
      Aphanius dispar, in controlling mosquito larvae, including the local malaria
      vector, Anopheles culicifacies adanensis. Cisterns, wells and barrels were found
      to be important breeding sites for the malaria vector and for culicine
      mosquitoes. Fish were equally effective in controlling mosquito larvae in all the
      types of breeding site investigated. The overall proportion of sites with fish
      that harboured mosquito larvae was 1.6%, ranging from 1.5 to 1.7% according to
      type of site, as compared to 34% in sites left unstocked, ranging from 17.9 to
      60.0%. Monthly restocking of fish where necessary was found to be sufficient to
      maintain an adequate level of control. Stocking of larvivorous fish in wells and
      household water storage containers was well-accepted by the participants, who
      were aware of the role of the fish in malaria prevention and found the fish
      useful in keeping their water free of other aquatic organisms. Based on the
      results of this study, larvivorous fish were introduced on an operational scale
      for the control of malaria transmission in Assab, with the voluntary
      participation of the population and the collaboration of the Municipality and
      health authorities of Assab.

PMID- 1363181
TI  - Malaria entomological inoculation rates in western Venezuela.
AB  - Over 61,000 anophelines collected between January 1988 and October 1989 in three
      villages in western Venezuela were assayed by ELISA for Plasmodium vivax
      circumsporozoite (CS) protein. The six specimens confirmed positive belonged to
      three species: Anopheles (Nyssorhynchus) nuneztovari Gabaldon, 1940, A.
      albitarsis Arribalzaga, 1878 sensu lato and A. oswaldoi (Peryassu, 1922). The
      estimated CS protein rate for all species combined was 0.01% (95% confidence
      limits 0.004-0.02%). This CS protein rate and the mean number of bites received
      by the collectors indicated a sporozoite inoculation rate of about 10.5 infective
      bites per person per year. From this value and the number of human malaria cases
      reported it was estimated that only 0.32% of bites by CS-positive mosquitoes led
      to a malaria infection. The CS protein rate is so low that this parameter would
      not be a practical indicator of the efficacy of control campaigns in this area.

PMID- 1363182
TI  - Evolution of the retrotransposons TRS/ingi and of the tubulin genes in
      trypanosomes.
AB  - The African trypanosomes have genomes of high plasticity, as demonstrated for
      instance by their ability to shuffle their genes around, coding for variant
      specific surface glycoproteins (VSGs). Another indication of their genome
      plasticity is the presence of multiple retro-elements. The retrotransposon-like
      element TRS/ingi is present in many copies in the genome of trypanosomes. One
      particular derivative of TRS/ingi, called TUBIS, had previously been found to
      interrupt a tubulin gene in a particular strain of T. brucei. Here both TRS/ingi
      and TUBIS were studied by hybridizing genomic DNA of various strains and species
      of trypanosomes with suitable probes in order to elucidate the evolution of this
      family of retro-elements. The TSR/ingi elements are highly repeated and have very
      long open reading frames, while TUBIS clearly is a truncated, inactivated form of
      this element, found in only one particular chromosomal location. Both elements
      were shown to be present in several strains and species of the subgenus
      Trypanozoon, in particular in T. brucei brucei, T. gambiense, T. rhodesiense, T.
      equiperdum and T. evansi. They could not be detected in species of other
      subgenera, in particular in T. congolense and T. cruzi. These findings suggest
      that the retrotransposon TRS/ingi was acquired by trypanosomes only after
      divergence of present day subgenera. The TUBIS element was found in exactly the
      same chromosomal location (at the 3' end of the tubulin gene cluster) in many
      different strains and species of the subgenus Trypanozoon. This shows that the
      element was transposed to this location before speciation of the subgenus.
      Although, TRS/ingi is unlikely to be involved directly in VSG switching, it may
      have contributed to the genome plasticity of trypanosomes.

PMID- 1363184
TI  - Mosquitoes and malaria transmission in irrigated rice-fields in the Benoue valley
      of northern Cameroon.

PMID- 1363183
TI  - Demographic findings relevant for health care planning and evaluation collected
      through a malaria control project in the Kivu Mountains, Zaire.
AB  - Population studies were conducted in the margin of a community based malaria
      control programme in the Katana Health zone, in the Eastern part of Zaire. The
      reported findings are based on prospective registration of vital events from
      March 1986 through February 1987. At mid term 28.083 people were covered. The age
      and sex structure of the population was typical for tropical Africa, apart from
      an excess of males to females after the age of 64. The mean age at marriage was
      21.2 years for women and 25.6 years for men. 89% of women did not complete a
      single year of formal education. The crude fertility rate was 250/1000 and total
      fertility 8.3 children. The infant mortality rate and the child mortality
      quotients attained 130/1000 and 183/1000 respectively. The crude death rate was
      23 per 1000 and the natural population growth rate 31/1000. Due to a net out
      migration of 28/1000 the zone's population remained, however, virtually stable.
      The latter observation questions the purported role of demographic pressure as a
      key determinant of the region's slow socio-economic development. The other
      findings provide valuable baseline and background information for planning and
      evaluating health-related activities.

PMID- 1363185
TI  - Distribution and severity of onchocerciasis in southern Benin, Ghana and Togo.
AB  - The Onchocerciasis Control Programme in West Africa has recently extended its
      operation in southern Benin, Ghana and Togo. To estimate the number of people
      infected and blinded by onchocerciasis and to describe the distribution and
      severity of the disease in the extension area, 99 villages were selected, using a
      stratified random sampling procedure, and surveyed. All the ecological and
      entomological information available was used in the sampling procedure and in the
      selection of 87 non-representative villages surveyed to confirm the findings. The
      study estimated that 590,468 people are infected and 11,715 blind from
      onchocerciasis out of a rural population of 1,878,234. The Pru, Asukawkaw and
      Mono river basins were areas with high risk of onchocercal blindness. The Oueme
      and Zou river basins in Benin and the mountainous areas between Ghana and Togo
      were classified as areas with medium risk of onchocercal blindness. The other
      parts of the study area presented low or no risk of onchocercal blindness. By
      detecting the river basins where villagers are at risk of onchocercal disease
      this study permits the selection of populations for disease control based on mass
      distribution of ivermectin, a microfilaricide.

PMID- 1363187
TI  - Ion-Motive ATPases: Structure, Function, and Regulation. Proceedings of a
      conference. Cleveland, Ohio, June 13-17, 1992.

PMID- 1363188
TI  - Proteases and Protease Inhibitors in Alzheimer's Disease Pathogenesis.
      Proceedings of a conference. Bethesda, Maryland, December 16-18, 1991.

PMID- 1363186
TI  - Factors affecting morbidity and mortality on-farm and on-station in the Ethiopian
      highland sheep.
AB  - Factors affecting morbidity and mortality of the Ethiopian highland sheep were
      studied both on-farm and on-station at Debre Berhan between 1989 and 1990.
      Primary causes of infectious origin resulted in high proportional morbidity
      (88.4% on-farm) and mortality (72.9% on-farm and 71.8% on-station) rates.
      Nutritional and managemental factors were also responsible for mortalities in
      lambs. The most frequent secondary causes of morbidity and/or mortality were
      ectoparasites and nasal myiasis. Health management interventions on-station were
      not high enough to produce performance improvements above the on-farm levels.
      However, the occurrence of gastrointestinal parasites significantly (P < 0.05)
      differed between the two management systems. The frequency of some of the major
      causes of morbidity and mortality such as pneumonia, fasciolasis and enteritis
      were significantly (P < 0.01) affected by season and age of an animal. In order
      to alleviate the major health constraints identified in this study, a proper
      health management intervention involving vaccination, strategic anthelmintic
      treatment and feeding management are suggested.

PMID- 1363189
TI  - Characterization of alternative routes for processing of the Alzheimer beta/A4
      amyloid precursor protein. Differential effects of phorbol esters and
      chloroquine.

PMID- 1363190
TI  - The development of manifest psoriatic lesions is linked with the invasion of CD8
      + T cells and CD11c + macrophages into the epidermis.
AB  - Koebner response was studied in 35 psoriatic patients. Two punch biopsies per
      patient were taken from non-lesional psoriatic skin before, and 6 h, 2 days, 7
      days, 14 days and 21 days after, tape stripping. Alterations in the numbers of
      CD1+ Langerhans cells, CD4+ and CD8+ T cells and CD11c+ macrophages were mapped
      morphometrically. Results were compared with lesional and non-lesional psoriatic
      skin, and control skin. Nine of 35 patients were Koebner-positive. No
      statistically significant differences were noted between non-lesional psoriatic
      and control skin. CD4+ T cells increased in number 2 days after trauma in both
      the epidermis and the dermis, whereas epidermal CD8+ T cells and CD11c+
      macrophages increased only in the Koebner-positive lesional skin after 7 days.
      The changes in lesions induced by tape-stripping resembled those seen in lesional
      psoriatic skin (mature plaques). The number of CD1+ cells increased in mature
      psoriatic lesions only. It seems possible that trauma per se stimulates the
      accumulation of CD4+ T cells at the site of injury, but the development of
      manifest psoriatic lesions correlates with invasion of CD8+ T cells and CD11c+
      macrophages into the epidermis.

PMID- 1363191
TI  - Effect of inorganic phosphate on hypoxanthine transport in isolated brain
      microvessels.
AB  - In isolated brain microvessels, used as an in vitro model of the blood-brain
      barrier, the rate of hypoxanthine uptake was modulated by the presence of
      inorganic phosphate. A single high-capacity, low-affinity transport system was
      apparently active in a phosphate-free medium (Vmax = 840 pmol/mg protein/min, Km
      = 750/uM); in the presence of 10 mM phosphate, there was also a low-capacity,
      high-affinity system (Vmax = 47 pmol/mg protein/min, Km = 27/uM). The phosphate
      dependent component was inactive in the absence of glucose or of Na+ ions, or
      upon addition of phloretine (but was scarcely affected by 2,4-dinitrophenol).
      This activity was apparently coupled to the intracellular
      phosphoribosyltransferase-catalyzed conversion of purines into the corresponding
      nucleotides: when inorganic phosphate was present in the suspending medium,
      labeled hypoxanthine was transported with higher efficiency and was readily
      converted to inosine monophosphate and to other related nucleotides. In the
      absence of phosphate ions, hypoxanthine was instead metabolized to xanthine and
      uric acid.

PMID- 1363192
TI  - Fractionation of gamma-glutamyl transpeptidase from the rat brain, kidney and
      pancreas by concanavalin A affinity chromatography.
AB  - gamma-Glutamyl transpeptidase (GGT) in tissue extracts from five brain regions,
      the kidney and pancreas of 50-day-old rats was examined for its specific activity
      and affinity to immobilized concanavalin A (Con A). According to their descending
      GGT activity, the tissue extracts were classified in the following order: kidney
      >> pancreas >> olfactory bulbs > medulla oblongata > hippocampus > cerebellum >
      frontal cortex. Using different concentrations of methyl-alpha-D-mannopyranoside
      for the elution of GGT from Con A-Sepharose column, the enzyme from brain regions
      could be separated into five fractions, two of which contained about 75% of the
      total GGT activity without regional differences in elution profiles. Almost
      complete GGT activity in kidney tissue extracts was eluted in a single peak
      whereas the enzyme from pancreas exhibited two peaks.

PMID- 1363193
TI  - Beneficial effects of befunolol on post-hypoxic recovery of cardiac contractility
      and myocardial metabolism.
AB  - The present study was undertaken to determine whether befunolol (BFE 60, CAS
      39543-79-8) a beta-adrenoceptor blocking agent, improves post-hypoxic contractile
      and metabolic recovery of perfused hearts. Isolated rat hearts were perfused for
      20 min under hypoxic conditions, followed by 45-min reoxygenation.
      Hypoxia/reoxygenation induced less than 5% post-hypoxic recovery of cardiac
      contractile force, incomplete return of resting tension of hearts, accumulation
      of tissue calcium, and release of purine nucleosides and bases, and creatine
      kinase from the heart. When hypoxic hearts were treated with 500 mumol/l
      befunolol from 0 to 10 min of hypoxic perfusion, marked recovery of contractile
      force (more than 50% of the pre-hypoxic value), complete suppression of the
      tissue calcium accumulation and significant suppression of the increase in
      creatine kinase activity of the perfusate were seen after reoxygenation. This
      treatment also significantly prevented the release of purine nucleosides and
      bases during hypoxia. These results suggest that treatment with befunolol during
      hypoxic perfusion is beneficial for post-hypoxic recovery of cardiac function and
      myocardial metabolism, probably through a mechanism of suppression of
      transmembrane flux of substrates, ions and enzymes. Cardiac contractile force
      upon the onset of hypoxia declined more rapidly and myocardial high-energy
      phosphate content after 10 min of hypoxia was significantly higher in befunolol
      treated hearts than in hearts without treatment. Thus, energy-sparing effects may
      also contribute to the beneficial post-hypoxic recovery of cardiac function and
      metabolism.

PMID- 1363194
TI  - Relative bioavailability of carbinoxamine and phenylpropanolamine from a retard
      suspension after single dose administration in healthy subjects.
AB  - The plasma pharmacokinetics of carbinoxamine (CA, CAS 486-16-8) and
      phenylpropanolamine (PP, CAS 14838-15-4) after single dose administration of a
      retard suspension (Rhinopront), containing a resinate as sustained-release agent,
      were compared to those of the same active principles given as an aqueous
      solution. The study was performed in 20 healthy subjects who received the two
      formulations according to a standard crossover design with a one-week wash-out.
      Blood samples were obtained up to 24 h post-dose. PP and CA were assayed in the
      plasma samples by gas chromatography with electron-capture detection and HPLC
      with coulometric detection, respectively. The pharmacokinetic results indicated
      sustained release of the two active principles with the retard suspension: CA
      appeared in plasma at a much slower rate than with the solution, a 30% lower Cmax
      being reached after 8.0 h instead of 3.0 h post-dose. For PP, Cmax was 23% lower
      and occurred 3.0 post-dose instead of 1.5 h with the solution. The extent of
      absorption of the two drugs, as assessed by AUC (0-24 h), was slightly smaller
      with the retard suspension than with the aqueous solution. However, the
      test/reference ratio remained within 95% confidence intervals of 80-87% and 88
      98% for CA and PP, respectively, indicating bioequivalence of the two
      formulations. A simulation of the plasma levels during repeated administration
      indicated that dosing with the retard suspension at 12-h intervals should yield
      the same steady-state plasma levels as a 5 times daily administration of a
      divided dose of the aqueous solution, for both drugs.

PMID- 1363196
TI  - [8th World Congress AIDS].

PMID- 1363195
TI  - Pharmacological treatment of allergies.
AB  - According to recent literature, the "anti-allergy" properties of antihistamines
      are linked to their antagonistic ability on receptor H1. In the majority of
      experimental models the immediate allergic responses is followed by a late phase.
      Especially at the pulmonary level, the presence of a late response after an
      allergic provocation is considered to correlate with the severity of asthma. The
      reference anti-allergy drugs, such as the inhaled corticosteroids or the
      cromones, without anti H1 activity, inhibit this late pulmonary response.
      Azelastine, ketotifen and cetirizine, three substances that are antagonistic to
      the anti-H1 receptor reduce the late pulmonary response. In addition, these three
      substances have other "anti-allergy" characteristics. Azelastine inhibits
      production of superoxide by the pulmonary neutrophils and eosinophils after PAF
      provocation in animals. Cetirizine significantly inhibits eosinophil infiltration
      in the bronchoalveolar lavage liquid in asthmatics with a late allergic
      bronchospasm. The presence of anti-histaminic and anti-allergy characteristics on
      the same molecule may perhaps convey a supplementary therapeutic benefit in the
      treatment of allergic symptoms.

PMID- 1363198
TI  - [The ultrastructural characteristics of the endocrine cells of the normal murine
      cecum and in experimental escherichiosis].
AB  - Ultrastructural investigations and a quantitative analysis of caecum endocrine
      cells were performed in the period from 15 minutes to 2 weeks after inoculation,
      using the model of experimental escherichiosis. The authors identified 5 types of
      endocrinocytes in the caecum of mice and showed the reaction of these cells:
      degranulation, extrusion of granules and their accumulation dependent on the time
      of the exposure.

PMID- 1363200
TI  - An even safer surgical environment.

PMID- 1363199
TI  - SDZ PSC-833--a novel potent in vitro chemosensitizer in multiple myeloma.
AB  - Multiple myeloma cell lines and patient tumor samples with and without the
      expression of the classical multidrug resistance (MDR) phenotype were
      investigated in vitro for drug induced cytotoxicity and modulation of drug
      resistance. Overall there was a good correlation in the cell lines between MDR
      expression, as measured by immunocytochemistry with monoclonal antibodies against
      P-glycoprotein 170 (Pgp), and in vitro resistance to doxorubicin (dox) and
      vincristin (vcr). Drug resistance in the cell line RPMI 8226 dox 40, expressing a
      high level of Pgp, was almost completely reversed by the novel non
      immunosuppressive cyclosporin A (CsA) analog SDZ PSC-833 (PSC), while the
      chemosensitizers verapamil, CsA and quinine, in clinically achievable
      concentrations, were much less effective. In cell lines with low Pgp expression,
      PSC and the other chemosensitizers seem equally effective. The patient tumor
      samples were selected to represent different combinations of Pgp expression, drug
      resistance and effects of chemosensitizers. PSC and CsA appeared equally potent
      and resistance modulation was detected not only in Pgp positive, but also in Pgp
      negative tumor samples. Furthermore, in one case of a Pgp expression myeloma,
      chemosensitizers were without effect. These findings indicate the need to
      incorporate in vitro chemosensitivity assays with Pgp determination when the
      effects of MDR modulating chemosensitizers are to be studied in the clinic.

PMID- 1363202
TI  - Occurrence of nasopharyngeal carcinoma in aboriginals of Taiwan: report of 14
      cases.
AB  - The authors describe the rare occurrence of nasopharyngeal carcinoma (NPC) in 14
      aboriginals of Taiwan (ABT), a minor ethnic group now accounting for less than 2%
      of the total population in Taiwan. The observation is epidemiologically unusual,
      representing a low-risk ethnic group in an NPC prevalent area. With regard to
      patient characteristics, symptomatology and pathology, we have not found any
      appreciable differences in reports from other geographic areas. Serological
      profiles of antiEBV-VCA (Epstein-Barr virus, viral capsid antigen) antibody in
      7/9 patients available for review of IgA and 5/7 patients available for review of
      IgG were found significantly elevated, ranging respectively from 1:40-640/1:160
      1280. Interestingly, 12 of the 14 patients were found to be exclusively from the
      Paiwan tribe residing in Pintung, a district in southern Taiwan. Since the exact
      prevalence of NPC in this minority remains unknown, it is not clear whether the
      apparent preponderance is real or merely causal due in part to geographic bias.
      To a lesser extent, however, our observations indicate that NPC is not an
      uncommon malignancy in Paiwan aboriginals of southern Taiwan.

PMID- 1363203
TI  - Lobar bronchioloalveolar carcinoma: an ultrasound study.
AB  - To assess whether chest ultrasound (US) can be useful in the diagnosis of lobar
      bronchioloalveolar carcinoma, we retrospectively analyzed the US patterns of
      eight patients with bronchioloalveolar carcinoma presenting with lobar
      consolidation. For comparison, 15 patients with lobar consolidation of a benign
      etiology were also analyzed. We found that the US patterns of lobar
      bronchioloalveolar carcinoma had a characteristic homogeneous, echogenic pattern.
      The air-bronchograms and air-alveolograms were scarce when compared to benign
      consolidation. The sensitivity of using these US criteria in discriminating lobar
      bronchioloalveolar carcinoma was 75%, and the specificity was 93%. We also
      assessed the yield of US-guided transthoracic cutting biopsies in the diagnosis
      of lobar bronchioloalveolar carcinoma. The diagnostic rate of the US-guided
      cutting biopsy was 100%, which was superior to other diagnostic procedures, such
      as sputum cytology (37%), fiberoptic bronchoscopy with brushing or biopsy (32%)
      and trans-thoracic needle aspiration cytology (50%). None of the patients
      developed complications. We conclude that the distinct US pattern for lobar
      bronchioloalveolar carcinoma is a helpful diagnostic sign, and the US-guided
      biopsy is a useful approach in the diagnosis of lobar bronchioloalveolar
      carcinoma.

PMID- 1363201
TI  - The effect of estrous cycle and buthionine sulfoximine on glutathione release
      from the in vitro perfused rat ovary.
AB  - There is little known regarding the intracellular mechanisms of modification of
      damage in the ovary. Ovarian perfusion of en block dissections of the rat right
      ovary with aorta and vena cava were done to determine (a) if glutathione (GSH) is
      released by the ovary, (b) if the release is cycle dependent, and (c) if GSH
      released is the product of de novo ovarian synthesis. All perfused ovaries
      released GSH and the release was maximal at estrus and least at metestrus.
      Perfusion with buthionine sulfoximine, a specific inhibitor of gamma
      glutamylcysteine synthetase, resulted in a dose-dependent reduction in GSH
      released, indicating inhibition of de novo synthesis during perfusion.

PMID- 1363204
TI  - Therapeutic effect of carbon dioxide laser versus single application of
      trichloroacetic acid for koilocytic squamous papillae.
AB  - This paper reports the treatment results of 50 symptomatic females who had
      clinical features of squamous papillae and histologic evidence of koilocytosis.
      Either a carbon dioxide laser or a single application of trichloroacetic acid
      (TCA) was used to treat these patients. All of the patients were alternately and
      prospectively randomized into one of two groups. Twenty-three of the 25 women
      treated by laser and 10 of the 25 women treated by TCA had resolution of either
      the symptoms or the vulvar lesions in a follow-up period ranging from six to 22
      months. Hence, we were able to control the symptoms and lesions in 92% of the
      women following initial laser treatment and 40% of the women following a single
      application of TCA. In addition, cosmetic results were satisfactory, and
      complications were minimal in the laser-treated group of patients. However, human
      papillomavirus DNA was still detected three to four weeks after treatment in 24%
      of the women treated by laser and 64% of the women treated by TCA. Whether they
      are at a higher risk of recurrence as compared to those without detectable viral
      DNA remains to be determined.

PMID- 1363197
TI  - [The mediator mechanisms of the ventral hippocampus in anxiety states formed by
      different aversive exposures].
AB  - Microinjections of monoamines and amino acids into rat ventral hippocampus showed
      functional relevance of GABA- or dopamine- and 5-HT-ergic mechanisms of this
      structure of brain formed by aversive actions of diverse biological importance
      rather than glutamate-ergic ones. The participation of hippocampus monoamine- and
      acidergic mechanisms in the origin of diverse aversive anxiety is discussed.

PMID- 1363205
TI  - Loop excision for cervical intraepithelial neoplasia.
AB  - We report the results of a prospective trial using a loop electrosurgical
      excision procedure (LEEP) on 97 patients with cervical intraepithelial neoplasia.
      In the LEEP group the mean cutting time and whole procedure time were 6.2 +/- 1.9
      seconds and 12.7 +/- 3.5 minutes, respectively. The average blood loss was 3.6 +/
      1.9 mL. In the control group (39 cases) using laser conization, the mean cutting
      time and whole procedure time were 11.7 +/- 3.5 minutes and 44.9 +/- 8.9 minutes,
      respectively. The average blood loss in the control group was 11.2 +/- 3.1 mL.
      The differences between the two groups were statistically significant. During
      LEEP surgery, four cases had accidental vaginal excision. There were three cases
      of late cervical bleeding after surgery; the surface of the cervix was smooth,
      and no adhesion or crypt formation was noted after re-epithelialization. Eight
      patients became pregnant after the loop excision and no cervical incompetence was
      noted during antenatal care. After a one-year follow-up period in the colposcopy
      clinic, there was no recurrence of cervical intraepithelial neoplasia in either
      group. We advise that among the modalities of treatment for cervical
      intraepithelial neoplasia, LEEP appears to offer patients several benefits such
      as less bleeding, precise specimens, local anesthesia, less cost and less
      discomfort. It is particularly suitable for treating younger women who have not
      yet completed their families.

PMID- 1363206
TI  - Effect of external load on isokinetic torque production by the knee in anterior
      cruciate ligament deficient patients.
AB  - The purpose of this study was to examine the effect of an external load on the
      isokinetic torque production of the knee directly from the anterior cruciate
      ligament (ACL) of deficient patients. Ten surgically proven ACL deficient
      patients were included in this study. Each patient was preoperatively studied
      using a Biodex isokinetic dynamometer. Isokinetic contraction of the quadriceps
      muscle and hamstring muscles were performed in five repetitions with an angular
      velocity of 45 degrees per second with proximal and distal pad placement,
      respectively. The results demonstrated that the ratio of torque production of the
      ACL deficient knee to the contralateral normal knee was greater in proximal pad
      placement than in distal placement and that the ratio of torque production of the
      knee in proximal pad placement to that of the knee in distal pad placement was
      greater in the ACL deficient knee than in the contralateral normal knee. Similar
      results were found for both extension and flexion of the knee. The results showed
      that ACL deficient patients felt more confident doing isokinetic contractions of
      the knee with proximal pad placement.

PMID- 1363207
TI  - Treatment of osseous defects with fibroblast-coated hydroxylapatite particles.
AB  - Several techniques of periodontal regeneration have been used, including
      hydroxylapatite (HA) grafting, demineralized free-dried bone allografts and
      guided tissue membranes, for which clinical merits still need further scientific
      study. The purpose of this pilot study was to examine the healing of periodontal
      defects using HA grafts coated with fibroblasts isolated from the periodontal
      ligament (PDL). We cultured fibroblast-like cells either from a clinically
      healthy site of the PDL or gingival tissues of the subject receiving the cell
      transplantation. We added HA to the cultures and allowed the cells to migrate
      onto the HA surface. Then the HA particles coated with cells were harvested and
      transplanted into the periodontal osseous defects of four patients after phase I
      treatment. Three HA grafts without coating cells were used as controls.
      Periapical x-ray and clinical parameters were monitored for up to six months.
      Scanning electron microscopy demonstrated that fibroblast-like cells had
      proliferated on the HA particles in vitro. Our results showed that the
      experimental group had greater pocket reduction and clinical attachment gain, and
      less gingival recession than did the control group at six months postoperatively.
      Periapical films revealed good filling of osseous defects in both groups. This
      study introduces a new biological approach for bringing PDL cells into intimate
      contact with root surfaces, in order to facilitate earlier repopulation of root
      surfaces with regenerative PDL cells.

PMID- 1363209
TI  - Rapid prenatal determination of fetal sex by polymerase chain reaction on
      amniocyte DNA.
AB  - Sex determination in early gestation is important for fetuses at risk for X
      linked disorders or congenital adrenal hyperplasia. One hundred and seventy
      consecutive samples of amniocytes were collected between the 12th and 31st
      gestational week. Seven women received early amniocentesis before the 14th week.
      Fetal sex was determined by amplification of Y-specific DNA fragments within five
      hours. All results of the polymerase chain reaction, except for one false
      negative, were compatible with cytogenetic analyses. Polymerase chain reaction of
      amniocyte DNA provides a rapid technique for sex determination in early gestation
      with high specificity and sensitivity.

PMID- 1363208
TI  - Reactivity of anti-mitochondrial antibodies in primary biliary cirrhosis and
      systemic sclerosis.
AB  - Anti-mitochondrial antibodies (AMA) were detected by indirect immunofluorescence
      in the sera of 16 out of 17 (94%) patients with primary biliary cirrhosis (PBC).
      Immunoblotting experiments with mitochondrial polypeptides from the porcine liver
      as antigens revealed that three antigens were recognized by the sera from AMA
      positive patients. These were a 70-kD protein recognized by nine out of 16 AMA
      positive sera, a 50-kD protein recognized by 13 out of 16 AMA-positive sera and a
      39-kD protein recognized by four out of 16 AMA-positive sera. The reactivity of
      these polypeptides was destroyed by brief exposure to trypsin. None of these
      antigens were recognized by any of the 30 control sera. These results show that
      the 70-kD, 50-kD and 39-kD proteins are the major mitochondrial autoantigens
      recognized by sera from patients with PBC. In addition, of 30 sera samples from
      patients with diffuse scleroderma, 13 reacted to the 70-kD and/or 50-kD antigens.
      Anti-centromere antibodies (ACA) were also detected in the sera of five of the 17
      (29%) patients with PBC. The high prevalence of ACA in patients with PBC and the
      presence of anti-70- and 50-kD antibodies in patients with diffuse scleroderma
      provide evidence of an association between these two disorders.

PMID- 1363210
TI  - Coronary artery bypass surgery utilizing right gastroepiploic artery.
AB  - Fifteen patients (10 men, 5 women), who underwent coronary artery bypass surgery
      utilizing the right gastroepiploic artery (R't GEAR) in combination with either
      the left internal mammary artery (LIMA) or the greater saphenous vein as graft
      material, were studied. The reasons for utilizing R't GEAR were previous coronary
      artery bypass operations with resulting marked wound adhesion prohibiting LIMA
      harvest (five cases), LIMA jeopardized during surgery (three cases), total
      arterial revascularization using LIMA + R't GEAR (four cases), and near total
      arterial revascularization using LIMA + R't GEAR + saphenous veins (SV) (three
      cases). A total of 40 coronary arteries were revascularized: the R't GEAR was
      used for revascularization of 11 left anterior descending arteries, three right
      coronary arteries, and one left circumflex artery; LIMA was used for
      revascularization of four left anterior descending arteries, and three diagonal
      arteries; the saphenous vein was used for revascularization of eight left
      circumflex arteries, three diagonal arteries, six posterior descending arteries,
      and one proximal right coronary artery. There were no hospital mortalities, and
      follow-up studies revealed satisfactory early results. From our preliminary
      experience with these 15 cases, we assume that the R't GEAR can be used as the
      graft material of choice for coronary artery bypass in cases where difficulty in
      LIMA utilization is encountered or insufficient vein graft conduit is available.
      It is particularly valuable in reoperations for coronary arterial disease.

PMID- 1363211
TI  - Open heart surgery in geriatric patients.
AB  - With the progress of medical science, the scope of open heart surgery has
      expanded. From 1975 through 1987, we operated on 114 consecutive patients aged 65
      years and over with the aid of a cardiopulmonary bypass in the Department of
      Surgery, National Taiwan University Hospital. The annual number of these elderly
      patients has increased gradually, reaching 6.4% of the annual open heart cases in
      1987. Eighty-six of our 114 patients were males and 28 were females. Their ages
      ranged from 65 to 88 years with an average of 68.5 years. Overall, 65 patients
      (57%) were operated on for coronary artery disease and/or its associated lesions;
      41 (36%), for valvular heart disease; six, for aortic dissection; two, for
      cardiac tumor; and one, for congenital pulmonary stenosis. One patient had
      combined coronary artery disease and aortic dissection. The mortality for
      isolated coronary artery bypass surgery was 12%; for single valvular surgery it
      was 11%. The complexity of the surgical procedure increased the operative
      mortality. The overall mortality was 23.6% (27/114), with subsequent death in
      5.7% during an average of 25 months of follow-up. Because of the degeneration of
      organ-systems in elderly patients, and its frequent association with poor cardiac
      reserve and other medical problems, these elderly cardiac patients should be
      checked thoroughly before they are considered for open heart surgery. Our
      experience suggests that open heart surgery can be done in selected patients aged
      65 years or older with acceptable risks. Age alone should not be an absolute
      contraindication to surgery, and clinical improvement is to be expected after
      surgery.

PMID- 1363212
TI  - Exercise thallium-201 tomographic scintigraphy in the diagnosis of coronary
      artery disease: emphasis on the effect of exercise level.
AB  - Exercise thallium-201 imaging using single-photon emission computed tomography
      (SPECT) was evaluated in 154 patients with angiographically documented coronary
      artery disease (CAD) and in 25 normal subjects. Of the 154 patients with CAD, 134
      (87%) had abnormal thallium images. By contrast, only 77 (50%) patients had
      ischemic ST-segment depression (p < 0.001). Among 25 normal subjects, 20 had
      normal exercise SPECT images. The specificity of exercise SPECT imaging (80% or
      20/25) in excluding patients with CAD was not significantly higher than that of
      exercise electrocardiography (76% or 19/25). For the detection of individual
      vessel involvement by analysis of territories of perfusion abnormalities, the
      sensitivity and specificity of exercise SPECT were 72% and 96% for the left
      anterior descending, 78% and 85% for the right coronary, and 47% and 98% for the
      left circumflex artery. Ninety (group 1) of the 154 patients with CAD achieved
      adequate exercise end points (ischemic ST-segment depression or > 85% of maximal
      predicted heart rate) and 64 (group 2) did not. Exercise SPECT showed
      significantly more perfusion abnormalities in group 1 than in group 2 (96% vs
      75%, p < 0.001). We conclude that: (1) exercise SPECT thallium imaging is more
      sensitive than exercise electrocardiography for detecting patients with CAD; (2)
      the sensitivity of the test is affected by the level of exercise; and (3) it is
      valuable in the identification of individual vessel involvement.

PMID- 1363213
TI  - Angiodysplasia as a source of intestinal bleeding: report of seven cases.
AB  - From October 1978 to April 1991, seven patients presenting at the National Taiwan
      University Hospital with gastrointestinal tract hemorrhage were diagnosed by
      colonofibroscopy or angiography as having angiodysplasia of the colon and small
      intestine. There were two men and five women; their ages ranged from 23 to 65
      years, with a mean age of 50.3 years. None of these patients were diagnosed by
      barium enema. Only two patients were diagnosed by colonofibroscopy, and six
      patients were diagnosed by angiography. Therefore, angiography was the most
      effective method for diagnosing angiodysplasia. A vascular tuft was the most
      frequent finding. Six patients with lesions on the right side of the colon
      underwent a right hemicolectomy, one patient with a lesion on the jejunum
      underwent a right hemicolectomy initially with segmental resection of the jejunum
      later. The postoperative courses were smooth, and there has been no further
      evidence of gastrointestinal blood loss or anemia in the follow-up period. A
      right hemicolectomy is the treatment of choice because these lesions are
      frequently multiple; the lesions are found primarily on the right side of the
      colon.

PMID- 1363215
TI  - Herpes esophagitis: a cause of upper gastrointestinal bleeding in an
      immunocompetent patient.
AB  - Herpes esophagitis presents as dysphagia and odynophagia in the majority of
      cases. Rarely has hematemesis been reported. We report a case of herpes
      esophagitis presenting with hematemesis in an immunocompetent patient. This 67
      year-old man suffered from herpes esophagitis, proven by a panendoscopic
      examination, with characteristic histological findings. He presented with
      hematemesis and passage of tarry stools, but was otherwise healthy with normal
      humoral, cell-mediated immunity and was negative for human immunodeficiency virus
      antibody. Only supportive treatment was given. He has been well for the past nine
      months since the initial diagnosis.

PMID- 1363214
TI  - Mosaic ring chromosome 13 analyzed by fluorescence in situ hybridization: report
      of a case.
AB  - A five-year-old boy with psychomotor retardation, microcephaly, bilateral
      cataracts, hearing impairment and hypospadia with microphallus was found to have
      multiple cell lines from peripheral blood: 46,XY/46,XY, -13,+r(13)/46, Xy, -13,
      +dic r(13) in the ratio of 35%/61%/4% by trypsin-Giemsa, and C-bandings. Using
      fluorescence in situ hybridization (FISH) with biotin-labeled alpha-satellite
      probe (D21Z1/D13Z1) and fluorescence staining (FITC), we confirmed that the ring
      originated from chromosome 13. To elucidate changes in the chromosome ends in the
      ring originated from chromosome 13. To elucidate changes in the chromosome ends
      in the ring formation, we used human telomere-specific probes for FISH study; it
      showed an absence of telomeres on the ring chromosome, although Ag-NOR staining
      was positive. These findings yielded different breaking points on the ends of
      both the short and long arms of chromosome 13 from those reported in the
      literature.

PMID- 1363216
TI  - Early diagnosis of a vein of Galen aneurysm: report of a case.
AB  - Congenital vascular malformation with an aneurysm of the vein of Galen is rarely
      seen, particularly in the prenatal period. With the advancement of diagnostic
      techniques such as ultrasonography, we were able to detect a case prenatally and
      to diagnose it postnatally.

PMID- 1363217
TI  - [Identification of a de novo mutation in a factor FVIII:C gene in a family
      requesting prenatal diagnosis of hemophilia A].
AB  - Hemophilia is caused by wide spectrum of different mutations in the F8C gene
      which made the direct DNA diagnosis of the diseases not the case of choice.
      Indirect DNA diagnosis by means of linked restriction fragment length
      polymorphisms (RFLPs) provides the alternative. Using this method authors
      identified de novo mutation in a family requiring prenatal diagnosis of
      hemophilia A. This de novo mutation arose during the spermatogenesis of the
      proband's father. Attempts to characterize the mutation on the molecular level
      are presented. (Ref. 15, Fig. 1.).

PMID- 1363218
TI  - [The effect of glycoside Tripterygium wilfordii Hook F on the immune regulatory
      function of T lymphocyte].
AB  - Previously, we treated successfully patients with systemic lupus erythromatosus
      (SLE) with glycoside Tripterygium Wilfordii Hook F, a Chinese medicinal herb. To
      evaluate the pharmacological mechanism of this herb, we studied its effects on
      the activation and proliferation facets of human T lymphocyte in vitro. The
      results revealed that this drug can markedly suppress the activation and
      proliferation facets of T lymphocytes.

PMID- 1363219
TI  - [Leptotrombidium scutellare in transmission of epidemic hemorrhagic fever virus].
AB  - To further elucidate the role of Leptotrombidium scutellare in transmission of
      epidemic hemorrhagic fever virus (EHFV), a series of studies were carried out
      from 1988 to 1990. EHFV was isolated from both larvae of free mites collected
      from the grassland of endemic areas and larvae of filial mites hatched in the
      laboratory. The suckling mice bitten by these larvae were infected by EHFV.
      Because only the larvae of chigger mite can bite vertebrate hosts and only take a
      full meal in its entire life cycle, the pathogen carried by it can only be
      originated from its parent mite via transovarial route. Thus it can be confirmed
      that the natural infection of EHFV in these mites is transferred via transovarial
      transmission. The results demonstrate that L (L.) scutellare can naturally be
      infected by EHFV; EHFV can be transmitted to the vertebrate host by biting of the
      larvae and can be transferred via transovarial transmission in mites; and
      therefore, L (L.) scutellare can serve as a transmitting vector of EHF.

PMID- 1363220
TI  - Esmolol--just another beta blocker?

PMID- 1363221
TI  - A comparison of fentanyl, esmolol, and their combination for blunting the
      haemodynamic responses during rapid-sequence induction.
AB  - The purpose of this randomized, double-blind study was to compare the ability of
      a combination of fentanyl and esmolol to blunt the haemodynamic effects of
      intubation with that of either agent alone. Patients received fentanyl or saline
      four minutes before, and esmolol or saline two minutes before rapid-sequence
      induction of anaesthesia. The F2 group (n = 24) received fentanyl 2 micrograms.kg
      1, the E2 group (n = 24) received esmolol 2 mg.kg-1, the F2/E2 group (n = 25)
      received a combination of fentanyl 2 micrograms.kg-1 and esmolol 2 mg.kg-1, and
      the F5 group (n = 26) received fentanyl 5 micrograms.kg-1. Following tracheal
      intubation, the maximum percent change from baseline heart rate was less in the
      F2/E2 and F5 groups (12% and 16% respectively) than in the E2 group (34%)(P <
      0.05). The maximum percent changes from baseline systolic blood pressure in the
      F2/E2 and F5 groups (15% and 6% respectively) were less than in the F2 and E2
      groups (24% and 33% respectively) (P < 0.05). The combination of a low dose of
      fentanyl and esmolol provides an alternative to a higher dose of fentanyl for
      blunting the haemodynamic responses to laryngoscopy and tracheal intubation
      during rapid-sequence induction in healthy patients.

PMID- 1363222
TI  - Anaesthetic management of a parturient with myocardial infarction related to
      cocaine use.
AB  - Cocaine abuse is common among parturients with an incidence of 11.8 to 20%.
      Myocardial infarction is a rare and lethal event during pregnancy with an
      incidence of 1 in 10,000 pregnancies. We present the anaesthetic management of a
      parturient of 36 wk gestation who suffered a myocardial infarction nine hours
      before delivery which was temporally related to "crack" cocaine use. The
      patient's cardiovascular system became unstable following cocaine use, and she
      required mechanical ventilatory support and pharmacologic stabilization guided by
      invasive haemodynamic monitoring. This patient survived a non-Q wave myocardial
      infarction, but the prognosis of peripartum myocardial infarction remains poor
      with a mortality rate of 30-40% which is increased if the infarction occurs in
      the third trimester or postpartum period. The optimal mode and timing of delivery
      after myocardial infarction is unresolved. The association between cocaine use
      and myocardial infarction was first described in 1982, and cocaine remains unique
      among local anaesthetics in its ability to compromise the cardiovascular system
      through both sympathomimetic effects and vasoconstrictive effects on coronary
      arteries. Because of the prevalence of substance abuse, cocaine use should be
      considered in the differential diagnosis of sudden cardiovascular compromise in
      parturients.

PMID- 1363223
TI  - Correlation of proliferative index (PCNA reactivity and Ki-67 reactivity) in
      primary breast carcinoma with hormone status, lymph node status, and disease-free
      survival.
AB  - The proliferative activity in 42 cases of breast cancer were assessed
      immunohistochemically using antibodies to proliferating cell nuclear antigen
      (PCNA) and Ki-67. These indices were correlated with the steroid receptor status,
      pathologic stage, and disease-free survival. There was a strong direct
      correlation between the two proliferation indices (r = .902, P < 0.001, Kendall's
      rank correlation). There was a weak correlation between the hormone receptor
      status and proliferation indices that was not significant when statistically
      tested. The cases were stratified into PCNA low proliferative index (PI) group (<
      4.5% positive cells) and PCNA high PI group (> 4.5% positive cells). In the low
      PI group, five of 18 (28%) patients were node-positive in contrast to eight of 14
      (58%) patients in the high PI group. After a follow-up period of 42-60 months, 14
      of 19 (74%) patients in the low PI group were disease-free compared to 10 of 17
      (53%) patients in the high PI group. The PCNA and Ki-67 proliferative indices
      appear to be of great prognostic value and may help identify a subset of breast
      cancer patients who should be given adjuvant therapy.

PMID- 1363224
TI  - MIS (Multicentric Isradipine Study of antihypertensive therapy).
AB  - One-year open Multicentric Isradipine Study (MIS) performed in 7 centres in
      Czechoslovakia included 144 patients with mild and moderate hypertension.
      Isradipine was given at a dose of 2.5 mg daily. If normalization of diastolic
      blood pressure (BP) had not been reached, the dosage was increased to 5 mg.
      Monotherapy with isradipine normalized diastolic BP in 44% of patients.
      Isradipine (5 mg daily) was combined with bopindolol in patients in whom
      isradipine alone failed to normalize diastolic BP. These had higher mean systolic
      and diastolic BP, body weight, erythrocyte and platelet counts at the beginning
      of the study. The combination of isradipine with bopindolol normalized diastolic
      BP in 87% of the group at the end of 48 weeks' treatment. Tolerance was excellent
      in 82% of patients. Treatment was discontinued in 8% patients, undesirable
      effects being the reason in 2%, ineffective therapy in 2% and poor adherence to
      therapy in 4%. Isradipine in monotherapy or in combination with bopindolol did
      not exert an adverse effect on the metabolic risk factors of ischaemic heart
      disease (cholesterol, glycaemia).

PMID- 1363225
TI  - Ultrabithorax is a regulator of beta 3 tubulin expression in the Drosophila
      visceral mesoderm.
AB  - beta 3 tubulin expression accompanies the specification and differentiation of
      the Drosophila mesoderm. The genetic programs involved in these processes are
      largely unknown. Our previous studies on the regulation of the beta 3 tubulin
      gene have shown that upstream sequences guide the expression in the somatic
      musculature, while regulatory elements in the first intron are necessary for
      expression in the visceral musculature. To further analyse this mode of
      regulation, which reflects an early embryonic specification program, we undertook
      a more detailed analysis of the regulatory capabilities of the intron. The
      results reveal not only a certain degree of redundancy in the cis-acting
      elements, which act at different developmental stages in the same mesodermal
      derivatives, but they also demonstrate in the visceral mesoderm, which forms a
      continuous epithelium along the body axis of the embryo, an early action of
      regulators guiding gene expression along the anterior-posterior axis of the
      embryo: an enhancer element in the intron leads to expression in a subdomain
      restricted along the anterior-posterior axis. This pattern is altered in mutants
      in the homeotic gene Ultrabithorax (Ubx), whereas ectopic Ubx expression leads to
      activity of the enhancer in the entire visceral mesoderm. So this element is
      likely to be a target of homeotic genes, which would define the beta 3 tubulin
      gene as a realisator gene under the control of selector genes.

PMID- 1363226
TI  - An amphioxus homeobox gene: sequence conservation, spatial expression during
      development and insights into vertebrate evolution.
AB  - The embryology of amphioxus has much in common with vertebrate embryology,
      reflecting a close phylogenetic relationship between the two groups. Amphioxus
      embryology is simpler in several key respects, however, including a lack of
      pronounced craniofacial morphogenesis. To gain an insight into the molecular
      changes that accompanied the evolution of vertebrate embryology, and into the
      relationship between the amphioxus and vertebrate body plans, we have undertaken
      the first molecular level investigation of amphioxus embryonic development. We
      report the cloning, complete DNA sequence determination, sequence analysis and
      expression analysis of an amphioxus homeobox gene, AmphiHox3, evolutionarily
      homologous to the third-most 3' paralogous group of mammalian Hox genes. Sequence
      comparison to a mammalian homologue, mouse Hox-2.7 (HoxB3), reveals several
      stretches of amino acid conservation within the deduced protein sequences. Whole
      mount in situ hybridization reveals localized expression of AmphiHox3 in the
      posterior mesoderm (but not in the somites), and region-specific expression in
      the dorsal nerve cord, of amphioxus neurulae, later embryos and larvae. The
      anterior limit to expression in the nerve cord is at the level of the four/five
      somite boundary at the neurula stage, and stabilises to just anterior to the
      first nerve cord pigment spot to form. Comparison to the anterior expression
      boundary of mouse Hox-2.7 (HoxB3) and related genes suggests that the vertebrate
      brain is homologous to an extensive region of the amphioxus nerve cord that
      contains the cerebral vesicle (a region at the extreme rostral tip) and extends
      posterior to somite four.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363227
TI  - Lox2, a putative leech segment identity gene, is expressed in the same segmental
      domain in different stem cell lineages.
AB  - The segmented tissues of the adult leech arise from a set of five, bilaterally
      paired embryonic stem cells via a stereotyped sequence of cell lineage.
      Individual segments exhibit unique patterns of cell differentiation, and previous
      studies have suggested that each stem cell lineage establishes at least some
      aspects of its own segmental specificity autonomously. In this paper, we describe
      a putative leech segment identity gene, Lox2, and examine its expression in the
      various stem cell lineages. Both sequence analysis and the segmental pattern of
      Lox2 expression suggest a specific homology to the fruitfly segment identity
      genes Ubx and abdA. In situ hybridization reveals a cellular accumulation of Lox2
      RNA over a contiguous domain of 16 midbody segments (M6-M21), including
      postmitotic neurons, muscles and the differentiating genitalia. Lox2 transcripts
      were not detected at the stage when segment identities are first established,
      suggesting that Lox2 gene products may not be part of the initial specification
      process. Individual stem cell lineages were labeled by intracellular injection of
      fluorescent tracers, and single cell colocalization of lineage tracer and
      hybridization reaction product revealed expression of Lox2 RNA in the progeny of
      four different stem cells. The segmental domain of Lox2 RNA was very similar in
      the various stem cell lineages, despite the fact that some stem cells generate
      one founder cell/segment, whereas other stem cells generate two founder
      cells/segment.

PMID- 1363228
TI  - Expression patterns of vHNF1 and HNF1 homeoproteins in early postimplantation
      embryos suggest distinct and sequential developmental roles.
AB  - The homeoproteins HNF1 (LFB1/HNF1-A) and vHNF1 (LFB3/HNF1 beta) interact with an
      essential control element of a group of liver-specific genes. During development,
      these putative target genes are initially expressed in the visceral endoderm of
      the yolk sac and subsequently in fetal liver. To assess the possible involvement
      of HNF1 and/or vHNF1 as transcriptional regulators in the early steps of visceral
      endoderm differentiation, we have analyzed the expression pattern of both factors
      both in vitro during differentiation of murine F9 embryonal carcinoma cells and
      in vivo during early postimplantation mouse development. We show here that
      differentiation of F9 cells into either visceral or parietal endoderm is
      accompanied by a sharp induction in vHNF1 mRNA and protein. By contrast, only low
      levels of aberrantly sized HNF1 transcripts, but not DNA-binding protein, are
      found in F9 cells and its differentiated derivatives. At 6-7.5 days of gestation,
      high levels of vHNF1 mRNA are present in the visceral extraembryonic endoderm,
      which co-localize with transcripts of the transthyretin gene. HNF1 transcripts
      are first detected in the yolk sac roughly two embryonic days later, after the
      developmental onset of transcription of target genes. As development proceeds,
      discrepancies are observed between the level of transcripts of both vHNF1 and
      HNF1 and their respective nuclear binding proteins, notably in the yolk sac and
      embryonic kidney. In addition, we show that two alternative spliced isoforms of
      vHNF1 mRNA, vHNF-A and vHNF1-B, are expressed in both embryonic and adult
      tissues. Taken together, these data suggest that vHNF1 participates as a
      regulatory factor in the initial transcriptional activation of the target genes
      in the visceral endoderm of the yolk sac, whereas the later appearance of HNF1
      could be required for maintenance of their expression. Our results also provide
      evidence of a posttranscriptional level of control of vHNF1 and HNF1 gene
      expression during development, in addition to the spatial restriction in
      transcription.

PMID- 1363231
TI  - Hepatocyte heterogeneity in the metabolism of fatty acids: discrepancies on
      zonation of acetyl-CoA carboxylase.
AB  - Lipid metabolism appears to be less zonated than carbohydrate and protein
      metabolism. Studies on the zonation of lipid metabolism have been centered in
      particular on fatty acid synthesis which, according to the concept of metabolic
      zonation, should be a predominantly perivenous process while fatty acid oxidation
      should be periportal. There are, however, conflicting data on the activity
      gradients of lipogenic enzymes as well as measurements of actual synthesis of
      fatty acid and very low density lipoprotein. Data obtained by microdissection
      show a 1.5- to 2-fold higher activity of acetyl-CoA carboxylase and citrate lyase
      in the perivenous zone in agreement with measurements of the actual rate of fatty
      acid synthesis in preparations of hepatocyte, enriched in periportal or
      perivenous cells. On the other hand, results obtained with the dual-digitonin
      pulse perfusion technique demonstrate the opposite gradient in the form of a 2-
      to 3-fold higher specific activity of acetyl-CoA carboxylase in the periportal
      zone based on measurements of the acetyl-CoA carboxylase protein proper. This
      specific activity gradient, which applies to male and not female rats, disappears
      almost completely in the fasted-refed animal, were lipogenesis is strongly
      induced. In this review we attempt to rationalize these discrepancies in the
      results as methodological differences which in particular apply to the following
      parameters: (1) expression of results (reference substance); (2) selectivity of
      zonal sampling, and (3) differences in methodology of acetyl-CoA carboxylase
      measurements. It is concluded that these factors could account for the
      discrepancies, but further studies, in particular on the zonation acetyl-CoA
      carboxylase mRNA, are required in order to further understand the zonation of
      lipid metabolism and its possible role in the metabolic regulation of the liver.

PMID- 1363230
TI  - Apical ridge dependent and independent mesodermal domains of GHox-7 and GHox-8
      expression in chick limb buds.
AB  - The homeobox-containing genes GHox-7 and GHox-8 have been proposed to play
      fundamental roles in limb development. The expression of GHox-8, by the apical
      ridge cells, and GHox-7, in the subridge mesoderm, suggests the involvement of
      these two genes in limb outgrowth and proximo-distal pattern formation. A
      straightforward way to test this is to remove the apical ridge. Here we report
      the relationship between the mesodermal expression of GHox-7 and GHox-8 and the
      apical ectodermal ridge in the chick limb bud. The data from ridge removal
      experiments indicate that there are at least two domains of GHox-7 expression in
      the apical limb bud mesoderm. The posterior subridge GHox-7 domain in the
      progress zone requires the influence of the apical ridge for continued
      expression, while the anterior GHox-7 domain continues expression after ridge
      removal. Posterior subridge mesoderm is exquisitely sensitive to the loss of the
      ridge in that GHox-7 expression by these cells is reduced in only two hours and
      undetectable by three hours after ridge removal. It would appear that one of the
      ways progress zone cells respond to the apical ridge signal is by expressing GHox
      7. The loss of ridge influence whether by growth at the apex or by ridge removal
      is followed by an unusually rapid decline in detectable GHox-7 transcripts.
      Maintenance of GHox-8 expression by the anterior mesoderm appears to be
      independent of the presence of the apical ridge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363229
TI  - Maintenance of the engrailed expression pattern by Polycomb group genes in
      Drosophila.
AB  - The stable maintenance of expression patterns of homeotic genes depends on the
      function of a number of negative trans-regulators, termed the Polycomb (Pc) group
      of genes. We have examined the pattern of expression of the Drosophila segment
      polarity gene, engrailed (en), in embryos mutant for several different members of
      the Pc group. Here we report that embryos mutant for two or more Pc group genes
      show strong ectopic en expression, while only weak derepression of en occurs in
      embryos mutant for a single Pc group gene. This derepression is independent of
      two known activators of en expression: en itself and wingless. Additionally, in
      contrast to the strong ectopic expression of homeotic genes observed in extra sex
      combs- (esc-) mutant embryos, the en expression pattern is nearly normal in esc-
      embryos. This suggests that the esc gene product functions in a pathway
      independent of the other genes in the group. The data indicate that the same
      group of genes is required for stable restriction of en expression to a striped
      pattern and for the restriction of expression of homeotic genes along the
      anterior-posterior axis, and support a global role for the Pc group genes in
      stable repression of activity of developmental selector genes.

PMID- 1363232
TI  - Dopexamine hydrochloride in the human heart: receptor binding and effects on cAMP
      generation.
AB  - Dopexamine hydrochloride is a synthetic catecholamine proposed for the short-term
      treatment of heart failure and postoperative low cardiac output. The
      pharmacological profile and anatomical localization of dopexamine binding were
      investigated in sections of right and left ventricle using [3H]-dopexamine and
      ligand techniques associated with light microscope autoradiography. Its effects
      on the 3-5-cyclic adenosine monophosphate (cAMP) generating system in membrane
      particles of the human right or left ventricle were also studied. [3H]-Dopexamine
      was specifically bound to sections of human right or left ventricle. The binding
      was time-, temperature- and concentration-dependent and was dissociable. The
      apparent equilibrium constant of dissociation was 3.5 nM. A decreased [3H]
      dopexamine binding capacity from the base to the apex and ventricles was
      noticeable. The pharmacological profile of [3H]-dopexamine binding to sections of
      right or left ventricle was consistent with the labelling of both beta 2
      adrenoceptors and dopamine DA-2 receptors. The most potent displacer of [3H]
      dopexamine was the beta 2-adrenoceptor antagonist ICI 118,551 followed by
      dopamine, noradrenaline and domperidone. The beta 1-adrenoceptor antagonist
      metoprolol or the dopamine DA-1 receptor antagonist SCH 23390 were ineffective as
      displacers of [3H]-dopexamine binding. Light microscope autoradiography revealed
      the localization of [3H]-dopexamine binding sites within the wall of the human
      right and left ventricle. The density of silver grains was slightly higher in the
      right than in the left ventricle and showed a uniform transmural distribution
      across the ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363233
TI  - 2-Chlorodeoxyadenosine, a "novel" agent in the treatment of both lymphoid and
      myeloid malignancies.

PMID- 1363234
TI  - Cancer chemotherapy does not enhance MDR-associated 170 kd glycoprotein
      expression in normal blood mononuclear cells.
AB  - BACKGROUND: The multidrug resistance (MDR) associated 170kd glycoprotein (P170)
      is expressed at a low level in normal and malignant cells, but in the latter it
      becomes frequently overexpressed after chemotherapy. This study evaluated P170
      expression in normal blood mononuclear cells after and during cancer
      chemotherapy. METHODS: P170 was detected by immunocytochemistry with two
      monoclonal antibodies (MRK-16 and JSB-1). RESULTS: P170 expression was low in all
      samples before, during and after chemotherapy. CONCLUSIONS: Cancer chemotherapy
      did not enhance P170 expression in normal peripheral blood mononuclear cells. The
      mechanisms enhancing P170 expression are likely to be more operative in tumor
      cells than in normal cells.

PMID- 1363235
TI  - Pyroglutamate aminopeptidase in rat submaxillary gland.
AB  - A significant amount of pyroglutamate aminopeptidase (PGAP) activity was found to
      be present in 27,000 x g supernatant of rat submaxillary gland, maximum activity
      being at pH 6.5. EDTA stimulated the enzyme activity by 95% at pH 8.0 while at pH
      6.5 it did not have any significant effect. On comparison of its properties
      submaxillary PGAP appears to be different from brain, pituitary and other
      reported PGAPs. Submaxillary PGAP could also catalyze efficiently the formation
      of cyclo (His-Pro) from TRH. Cyclo (His-Pro) formation by submaxillary enzyme was
      more pronounced than that by liver PGAP.

PMID- 1363236
TI  - Generation and cytotoxic profile of human peripheral blood CD4+ T lymphocytes.
AB  - The effects of a variety of metabolic and anti-tumour necrosis factor (TNF)
      antibodies were utilized to distinguish several different mechanisms of
      cytotoxicity employed by CD4+ effectors isolated from human peripheral blood
      lymphocytes (PBL). PBL, unseparated high buoyant density T cells and their CD4+ T
      cell subsets were activated with anti-CD3 monoclonal antibody (MoAb) and
      interleukin-2 (IL-2) for 1-5 days. CD4+ T cells activated with IL-2/anti-CD3 MoAb
      were cytotoxic when directed by a bispecific anti-nitrophenyl (NP)-anti-CD3 MoAb
      heteroconjugate against both NP-modified nucleated target cells (TC) and non
      nucleated sheep red blood cells (SRBC). This CD4+ T population also lysed L929 in
      a TNF-alpha dependent manner. Interestingly, different mechanisms of nucleated
      and non-nucleated TC directed lysis by CD4+ effectors were implied by distinct
      patterns of sensitivity to cholera toxin (CT) and cyclosporin A (CsA).
      Cyclosporin A and CT inhibited CD4+ T cell directed lysis of SRBC, but not EL4.
      Cholera toxin, CsA or EGTA pretreatment also significantly inhibited the release
      of alpha-N-benzyloxycarbonyl-L-lysine-thiobenzylester (BLT)-esterase activity
      suggesting that degranulation of CD4+ effectors may be a critical step in their
      redirected lysis of SRBC. Overall, these findings suggested that activated human
      peripheral blood (PB) CD4+ effectors can lyse TC by at least three distinct
      mechanisms: (i) a CsA-sensitive directed lysis of SRBC which correlates with
      exocytosis and presumably occurs via membrane lesions; (ii) a CsA-insensitive
      directed lysis of NP-modified nucleated TC that does not appear to involve
      exocytosis and is metabolically distinct; and (iii) a direct TNF-dependent lysis
      of TNF-sensitive TC. The highly proliferative CD4+ T cell population could be
      propagated for at least 35 days while retaining cytotoxicity and secreting up to
      80 U/mL of IL-2. These data raise the possibility that anti-CD3 MoAb plus IL-2
      activated CD4+ T cells may prove effective in adoptive tumour immunotherapy.

PMID- 1363237
TI  - An analysis of hypotensive effect of synthetic oxytocin in rabbit.
AB  - Intravenous injection of synthetic oxytocin (Syntocinon) causes a fall of blood
      pressure in rabbit. The hypotensive response was potentiated after vagotomy and
      atropine. Beta-adrenergic and 5-HT blockers reduced the hypotensive response to
      oxytocin. Hypotensive response of oxytocin in rabbit involves two factors,
      activation of beta-adrenergic receptor and release of 5-HT.

PMID- 1363238
TI  - Lasertripsy in the treatment of ureteral lithiasis.
AB  - We submit our experience with laser treatment for ureteral lithiasis. We used the
      laser Candela MDL 2000 for the treatment of 62 lithiases (40 at the pelvic
      ureter, 16 at the iliac ureter and 6 at the lumbar ureter) in 58 patients. A semi
      rigid Dretler or Gautier multiscope were used. Of the 62 calculi complete
      fragmentation was not achieved in 4 and they were ascended to the renal pelvis
      for subsequent ESWL. In 51% of the patients the ureteral catheter was left for 24
      hours, and a double-J stent was used in two cases. COMPLICATIONS: 2 simple
      perforations of the ureter that were solved by means of a double-J stent;
      occasionally petechiae on the ureteral wall and two cases of rupture of the laser
      fibre tip that was easily removed with a forceps.

PMID- 1363240
TI  - Use of human chorionic gonadotropin stimulation test to detect a retained testis
      in a cat.
AB  - A 4-year-old male cat was referred because of aggressive behavior and spraying
      urine. When the cat was 6 months old, only 1 testis was found in the scrotum.
      When the cat was 1 year old, the scrotal right testis was surgically removed and
      the left testis was not found, either within the scrotum or within the abdomen.
      The cat developed male behavior and another laparotomy was performed 1 year
      later, at which time the left testis could not be located. The cat continued to
      show male behavior. On referral, the penis was well developed and had spines.
      Human chorionic gonadotropin (HCG), 500 IU, was administered IV. At baseline, 30,
      and 120 minutes after HCG administration, serum testosterone activity (ng/ml) was
      0.68, 5.0, and 10.5, respectively. Laparotomy was performed with the cat under
      general anesthesia. The left testis was found in the facial plane lateral to the
      symphysis pubis. Six weeks after the surgery, the HCG stimulation test was
      repeated and testosterone was not detected in any serum sample. The most
      practical solution to locate the undescended testis would have been to follow the
      intact ductus deferens to the testis adjacent to the pubic symphysis.

PMID- 1363239
TI  - Systemic necrotizing vasculitis in nine young beagles.
AB  - A systemic necrotizing vasculitis of unknown etiopathogenesis may be termed
      juvenile polyarteritis syndrome (JPS). The syndrome has been recognized primarily
      in young Beagles used for toxicologic studies. We studied 9 young Beagles with
      JPS. Affected dogs had fever (40 to 41.5 C), anorexia, and signs of pain in the
      cervical area. They had a characteristic hunched stance, and were unwilling to
      move. Laboratory abnormalities in all dogs included nonregenerative anemia,
      hypoalbuminemia, and leukocytosis characterized by a mature neutrophilia.
      Analysis of CSF revealed a moderate to severe neutrophilic pleocytosis and a
      mildly high protein concentration in most dogs. Signs of disease resolved rapidly
      with high doses (2.2 mg/kg of body weight, PO) of prednisone. If untreated,
      clinical signs and laboratory abnormalities had a remitting and relapsing course
      in most dogs. Findings at necropsy included necrotizing arteritis with fibrinoid
      necrosis, periarteritis, thrombosis, and intimal proliferation that most
      frequently affected small- to medium-sized vessels in the cervical spinal cord,
      mediastinum, and heart. An immune-mediated pathogenesis for this disease is
      suspected.

PMID- 1363241
TI  - [Surgical therapy of chronic pancreatitis].

PMID- 1363242
TI  - Quantitative analysis of immunocompetent cells in human periapical lesions:
      correlations with clinical findings of the involved teeth.
AB  - Human periapical lesions develop as a result of a pathological immune response to
      continuous stimuli from infected root canals. This study identified the
      immunocompetent cells in such lesions immunohistochemically and quantified them
      to examine their interrelationships and correlations with clinical findings. The
      number of IgG-containing cells in CD4+ cell (Th/i)-rich lesions (> or = 55 CD4+
      cells/2 x 10(4) microns 2) was significantly larger than in CD4+ cell-poor
      lesions (< 55 CD4+ cells/2 x 10(4) microns 2). This indicated that the CD4+ cells
      and the IgG-containing cells acted together against antigenic stimuli. The
      proportion of T cells in the mononuclear infiltrates varied with the size of the
      periapical lesions. The proportion of CD11+ cells (monocytes/macrophages) was
      significantly larger in lesions which showed a positive reaction to percussion or
      were tender on palpation than in the lesions without these symptoms. These
      observations suggest that T cells may play an important role in the development
      of periapical lesions and that CD11+ cells may be involved in the development of
      symptoms.

PMID- 1363243
TI  - [Urinary N-acetyl-beta-D-glucosaminidase and gamma-glutamyl-transpeptidase
      activities for evaluation of renal disturbance in patients with multiple
      myeloma].
AB  - The activities of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl
      transpeptidase (gamma-GTP) and NAG isoenzyme were measured in the urine of 20
      patients with multiple myeloma (IgG/IgA type/Bense Jones type; 15/1/4 cases) and
      25 healthy controls to evaluate these activities as indicators of renal
      disturbance in multiple myeloma. NAG isoenzyme fractions in urine were measured
      by agarose electrophoresis-m-cresol sulfonphthaleinyl-NAG reaction. Mean urinary
      NAG activity in the patients with myeloma was significantly higher than that in
      the controls (20.1 +/- 3.3 vs 4.3 +/- 0.3U/g. cr; p < 0.001). Urinary NAG
      activity in these patients correlated positively with the dose (mg/g. cr) of
      urinary protein (r = 0.755; p < 0.01), most of which were considered to be light
      chain protein, but not with creatinine clearance. Each urinary NAG isoenzyme
      fraction (NAG-1, -2, -3) was higher in the patients than that in the controls,
      and especially NAG-2 fraction (A form) showed a highly positive correlation with
      the dose of urinary protein. Urinary gamma-GTP activity in the patients did not
      differ from that in the controls, but urinary NAG/gamma-GTP ratio was higher in
      the patients, and reversely correlated with creatinine clearance (r = -0.721; p <
      0.01). It is suggested that the elevation of urinary NAG activity results from
      the damage of lysosome in proximal tubular cells by urinary light chain protein
      and its degradation products. Therefore, urinary NAG activity may be a good index
      for proximal tubular disturbance, and NAG/gamma-GTP ratio may be an index for the
      extensive damage of nephrons in addition to the damage of tubular cells in
      multiple myeloma.

PMID- 1363244
TI  - [Indications and timing of the most frequent elective pediatric surgery
      interventions].
AB  - The most common surgical diseases in childhood that need a planned operation, are
      described--especially the indications and the timing of operation. Inguinal
      hernia, hydrocele, cryptorchism, umbilical hernia and phimosis are presented.

PMID- 1363246
TI  - 19th Symposium on Nucleic Acids Chemistry. Proceedings. Fukuoka, Japan, November
      11-13, 1992.

PMID- 1363245
TI  - [Genetics and hyperphenylalaninemias in 1992].
AB  - Hyperphenylalaninemias result from different enzymatic impairment, the most
      common and best studied which is phenylalanine hydroxylase (PAH) deficiency. The
      PAH gene has been cloned, sequenced and mapped: it is a single copy. Twenty-one
      mutations have now been characterized, but they constitute less than half of the
      haploid genotypes in French patients. A study of RFLP haplotypes is informative
      in 90% of families, but no linkage disequilibrium exists between illness and one
      particular haplotype. Prediction of phenotype from genotype seems possible, and
      could constitute a better therapeutic approach, perhaps including gene therapy in
      the most serious cases. The recently produced murine model should permit further
      progress to be made. Some hypotheses could be put forward about the origin and
      high frequency of this disease, that principally affects Caucasians: there is a
      consensus of opinion--though there is no definitive proof--that some selective
      advantage exists in individuals heterozygous for a PKU allele.

PMID- 1363247
TI  - Isolation of a new human pseudogene for proliferating cell nuclear antigen.
AB  - A new gene, which cross-hybridized with a rat PCNA cDNA probe, has been isolated
      from a human genomic cosmid library. A comparison of the gene with the human PCNA
      cDNA revealed 71% homology for the nucleotide sequences. This gene completely
      lacks introns and has traces of a polyA tail which the messenger RNA of the
      active gene retains. These facts indicate that this gene was generated by the
      reverse-transcription of a processed RNA for PCNA and exists as a PCNA pseudogene
      in the human genome.

PMID- 1363250
TI  - Failure to replicate linkage between chromosome 5q11-q13 markers and
      schizophrenia in 28 families.
AB  - Sherrington et al. (1988) reported linkage between markers located on the 5q11
      q13 region of chromosome 5 and schizophrenia in five Icelandic and two British
      families. To date, however, all attempts to replicate the initial finding have
      failed. Using three markers of chromosome 5, we have studied 28 additional French
      pedigrees. When our data were analyzed both with parametric (i.e., lod scores)
      and nonparametric methods, we found no evidence of linkage. Thus, we were unable
      to replicate the earlier report by Sherrington et al.

PMID- 1363248
TI  - 'Telephobia'.

PMID- 1363249
TI  - The neuroanatomical basis of anxiety.
AB  - This review details the neural systems that are important in anxiety-related
      behaviours. In particular, the role of the amygdaloid complex, Papez circuit,
      septohippocampal formation and raphe nuclei are described and discussed. Evidence
      is gathered from a variety of experimental approaches. These include behavioural
      assessment of anxiety in animals after intracerebral injection of pharmacological
      agents and following lesions of discrete brain nuclei and selective
      neurotransmitter pathways. Further evidence is provided by functional brain
      mapping studies applied to animals and humans. It is proposed that the neural
      systems recruited in different experimental conditions of anxiety may differ,
      supporting the notion that clinical anxiety exists in several forms. This has
      implications for the identification of new anxiolytic treatments. In particular,
      the findings suggest that approaches aimed at identifying new anxiolytic agents
      must take into account both the distribution of receptors for the drug and the
      neuronal systems activated by the experimental protocol.

PMID- 1363251
TI  - Regulation of somatostatin and growth hormone-releasing factor by gonadal
      steroids in fetal rat hypothalamic cells in culture.
AB  - The mechanism underlying the sexually dimorphic pattern of growth hormone (GH)
      secretion in the rat has not been clearly elucidated. In the present study, we
      assayed the possible direct effect of gonadal steroids on both somatostatin (SS)
      and growth hormone-releasing factor (GRF) in fetal rat hypothalamic cells in
      culture. Hypothalamic cells, obtained by mechanical dispersion, were maintained
      as monolayer cultures in serum-supplemented medium. After 20 days in culture,
      cells were incubated with serum free medium containing testosterone (T, 10, 20,
      40 ng/dl) or estradiol (E, 0.1, 1, 10 ng/dl) for 48 h. At the end of the
      experiments, immunoreactive SS (IR-SS) and immunoreactive GRF (IR-GRF) were
      measured by specific radioimmunoassays (RIAs) in media and cell extracts. After
      48 h of incubation with testosterone, somatostatin in both media and cells was
      significantly reduced. On the contrary, this treatment lead to a dose-dependent
      increase in media and cell GRF content. When cells were incubated with estradiol
      for 48 h, a significant inhibition in medium SS release was observed, whereas
      intracellular SS slightly increased at the highest concentration of 10 ng/dl.
      Estradiol treatment resulted in an inconsistent decrease in media and cells IR
      GRF. Our results indicate that both SS and GRF are under the influence of
      testosterone and estradiol acting at the hypothalamic level, and furthermore
      suggest that at this stage of brain development, gonadal steroids may regulate GH
      secretion through their ability to modulate hypothalamic SS and GRF.

PMID- 1363252
TI  - Role of CD8+ in late opportunistic infections of patients with AIDS.
AB  - We studied the relationship of CD4+ and CD8+ depletion to initial and late
      opportunistic infections in 62 patients with AIDS. The mean interval between
      initial and late infections was 12.2 months. Geometric mean (and 95% confidence
      intervals) of T-cell counts at the diagnosis of each infection were:
      (Pneumocystis carinii pneumonia) CD4+ 0.051 (0.044-0.058) x 10(9)/l, CD8+ 0.561
      (0.476-0.646) x 10(9)/l; (cytomegalovirus retinitis) CD4+ 0.025 (0.019-0.031) x
      10(9)/l, CD8+ 0.333 (0.183-0.483) x 10(9)/l. Mycobacterium avium-intracellulare
      bacteraemia closely followed cytomegalovirus dissemination. Most patients were
      free from late opportunistic infections caused by disseminated cytomegalovirus
      and M. avium-intracellulare until CD8+ declined below 0.500 x 10(9)/l. Zidovudine
      improved CD4+, but less so CD8+, and similarly enhanced the survival of patients
      treated in 1985-1990 and 1991.

PMID- 1363253
TI  - [Which medical treatment after myocardial infarction?].
AB  - Patients leaving the hospital after a myocardial infarction are given a
      prescription containing several drugs. The purpose of this paper is to determine
      which of these drugs have a proven value and for which types of patients.
      Antithrombotic agents (be it acetyl-salicylic acid or antivitamin K drugs) have
      been shown to be efficient after a myocardial infarction. Beta-blockers are
      certainly useful, notably in cases with severe necrosis. Conversely, the
      usefulness of calcium antagonists for secondary prevention has not been
      demonstrated and indeed, it seems probable that the drugs of this class might be
      harmful in patients who had severe infarction. There is little divergence
      concerning the necessity to control the risk factors for coronary atherosclerosis
      after a myocardial infarction. The evidence is strong concerning giving up
      smoking; it is intuitive as regards controlling arterial hypertension and more
      controversial as regards the need for lowering blood cholesterol levels. The
      systematic prescription of antiarrhythmic agents after myocardial is certainly
      noxious. Finally, prospects are now opened by the prevention of left ventricular
      remodelling under treatment with angiotensin-converting enzyme inhibitors.

PMID- 1363254
TI  - Tolerance during dosing with H2-receptor antagonists. An overview.
AB  - Diminution of antisecretory effect of H2-receptor antagonists with repeated oral
      dosing, termed tolerance, has been established in healthy volunteers. Anecdotal
      evidence indicates the development of tolerance with intravenous dosing. These
      findings demonstrate that tolerance may be clinically relevant in diseases where
      tight control of acidity is required. Patients with duodenal ulcer disease,
      however, do not develop significant tolerance, according to the sparse
      investigations available. Tolerance will, at most, only be of minor clinical
      significance in failures of DU to heal. The mechanisms implicated in the
      development of tolerance remain unclear.

PMID- 1363255
TI  - [Congress of the North American Nursing Diagnosis Association (San Diego, 1992)].

PMID- 1363256
TI  - On the relationship between the inhibition of thrombin stimulated aggregation and
      thromboxane formation in isolated platelets treated with beta-adrenoceptor
      blocking drugs.
AB  - Thromboxane B2 (TXB2) formation in isolated, thrombin-stimulated rat platelets
      was time dependent and appeared after 5 s of incubation. Beta-adrenoceptor
      blocking (BAB) drugs inhibited thrombin-stimulated TXB2 formation in the
      following rank order of potency: metipranolol approximately alprenolol
      approximately propranolol > oxprenolol > practolol. Atenolol was ineffective in
      inhibiting TXB2 production in stimulated platelets. The inhibition of thrombin
      stimulated TXB2 formation by BAB drugs correlated with their inhibitory effect on
      thrombin-stimulated platelet aggregation, arachidonic acid liberation from
      membrane phospholipids and with their membrane fluidization. The higher was the
      liposolubility of the beta-adrenoceptor blocking drugs investigated, the higher
      was their inhibition of stimulated TXB2 formation. Hydrophilic, selective
      atenolol and practolol revealed slight or no inhibitory effect on stimulated
      thromboxane production.

PMID- 1363257
TI  - The use of dopexamine after cardiac surgery: acute and long-term effects in
      patients with impaired cardiac function.
AB  - The haemodynamic efficacy of dopexamine, a beta 2-adrenergic agonist with
      dopaminergic activity, was evaluated during dosetitration and longterm infusion
      in 20 cardiosurgical patients with low cardiac output following coronary artery
      bypass grafting and/or valve replacement or repair. After infusion of four doses
      (1, 2, 4, and 6 micrograms/kg/min), the dose producing the optimal response was
      administered for up to 36 h. Dopexamine infusion resulted in a dose-dependent
      significant increase in cardiac index (CI: 2.2-->3.3 L/min/m2) associated with a
      marked reduction of systemic vascular resistance (SVR: 1820-->1144 dyn.sec.cm-5).
      Heart rate increased significantly (HR: 89-->117 beats/min), while mean arterial
      blood pressure remained unchanged (MAP: 94-->89 mmHg). Unwanted effects
      (tachycardia and hypotension) were chiefly seen at higher doses (-->4
      micrograms/kg/min). The beneficial haemodynamic effects were well maintained
      during the extended infusion period up to 36 hours at a mean dopexamine dose of
      2.8 micrograms/kg/min. At these low doses, the positive chronotropic response to
      the drug remained within the limits of clinical acceptability. During long-term
      infusion up to 36 hours there was no indication of tolerance or an effect
      attenuation. It can be concluded that dopexamine acting as "inodilator" with
      dopaminergic properties is an useful adjunct to the pharmacological spectrum in
      the management of low-output states following cardiac surgery.

PMID- 1363258
TI  - Imaging of the testicle: the painful scrotum and nonpalpable masses.
AB  - Scrotal pain is initially evaluated by color Doppler ultrasonography providing
      information on the presence or absence of flow within the testis and B Scan
      imaging providing important complementary information about lesions such as
      torsion of the appendix testis and testicular abscess. While radioisotope
      scanning provides similar information to color Doppler about testicular flow, it
      does not demonstrate the anatomy. Testicular imaging is extremely sensitive for
      "silent masses" and useful to evaluate palpable ones. Characteristic findings may
      be seen with simple testicular cysts and epidermoid cysts. Homogeneously
      hyperechoic masses have a variety of etiologies but are virtually always benign.
      A major limitation of a ultrasonography is the large number of nonneoplastic
      lesions which may mimic tumors.

PMID- 1363259
TI  - [Primary and secondary prevention in hypertensive patients. An assessment of
      current status].
AB  - The effect of a long-term treatment with beta-receptor-antagonists after an
      established myocardial infarction is generally accepted. Beta-receptor
      antagonists without intrinsic sympathicomimetic activity should be used,
      cardioselectivity is of lesser importance, except in patients with special
      problems (i.e. increased bronchial resistance, decreased peripheral blood flow
      etc.). Hydrophilic or lipophilic properties do not play any role. For primary
      prophylaxis in older hypertensives diuretics are the drugs of first line, in
      patients with high risk for heart- and blood-vessel diseases however beta
      receptor-antagonists--eventually in combination with low doses of diuretics
      should be chosen.

PMID- 1363260
TI  - [New anti-arrhythmia agents].
AB  - Use of class-I antiarrhythmic agents (encainide, flecainide or moricizine) to
      suppress asymptomatic ventricular premature depolarizations does not decrease,
      but rather increases mortality from cardiac events after myocardial infarction.
      These patients should not be treated with antiarrhythmic drugs until improved
      survival is shown in a controlled clinical trial. In other clinical conditions
      such as symptomatic tachyarrhythmias class-I agents should only be used if the
      expected benefit outweighs the risk of an adverse cardiac effect. The development
      of new class-I drugs does not seem promising. Esmolol is the first intravenous
      and ultrashort-acting beta-adrenoceptor blocker that can be used to treat
      supraventricular arrhythmias in the critical care setting; in addition, it
      displays high cardioselectivity. Specific class-III antiarrhythmic agents
      including sematilide and dofetilide have been shown to be effective against
      ventricular tachyarrythmias in preclinical studies, but their clinical value
      remains to be established. Torsades de pointes arrhythmia is an undesirable side
      effect closely coupled to specific class-III action that may limit their future
      use. The known pharmacological profiles and limited controlled clinical studies
      make amiodarone and sotalol promising candidates for drugs that may improve
      survival of patients at risk for sudden cardiac death.

PMID- 1363261
TI  - [Beta receptor blockers in dilated cardiomyopathy (clinical aspects)].
AB  - Results of 16 international published studies (with a total of 397 patients in
      NYHA-classes II-III) concerning chronic therapy with beta-adrenoceptor blockade
      in idiopathic dilated cardiomyopathy were analyzed. 8 studies were placebo
      controlled. Under beta-blockade cardiac output increased significantly by about
      15% and ejection fraction by approximately 30%, apparently due to an improvement
      in contractility and relaxation of LV myocardium. Therapy was tolerated without
      complications in 93% of patients when the loading dose was 5 to 15 mg
      metoprolol/d (or equivalent) and a long-term dose of 100-200 mg/d metropolol (or
      equivalent) was reached within 4 weeks. Patients with severe heart failure (NYHA
      IV) had a higher risk of complications. A positive effect of beta-blockade in IDC
      was achieved in most cases but not earlier than after 2-3 months after initiating
      therapy. Despite these positive results beta-blockade in patients with IDC may
      not yet be recommended generally. Sufficient results of controlled trials are
      still lacking. Important questions with regard to the prognosis under beta
      blockade, to the effects of cardioselectivity and intrinsic activity, and to the
      efficacy of this kind of therapy in the presence of ACE inhibitors have not been
      answered. Thus, major trials with controlled design are needed.

PMID- 1363262
TI  - [Importance of beta 2-adrenergic receptors in heart failure].
AB  - Substantial evidence has accumulated that in the human heart both beta 1- and
      beta 2-adrenoceptors coexist. As a rule, the amount of beta 2-adrenoceptors is
      higher in the atria (about 30% of the total beta-adrenoceptor population) than in
      the ventricular myocardium (about 20%). Both beta 1- and beta 2-adrenoceptors
      couple to adenylate cyclase and mediate positive inotropic effects of
      isoprenaline and adrenaline on isolated, electrically driven cardiac
      preparations. In the atria, stimulation of both beta 1- and beta 2-adrenoceptors
      causes maximal increases in contractile force; in the ventricular myocardium,
      however, only beta 1-adrenoceptor stimulation maximally increases contractile
      force, whereas beta 2-adrenoceptor stimulation evokes only submaximal increases.
      On the other hand, noradrenaline induces its positive inotropic effect on atrial
      and ventricular preparations solely via beta 1-adrenoceptor stimulation. Because
      nordadrenaline is the main transmitter of the human sympathetic nervous system,
      this indicates that under normal physiological conditions, the heart rate and
      contractility are under the control of cardiac beta 1-adrenoceptors, whereas
      cardiac beta 2-adrenoceptors play only a minor role, if at all. However, in
      situations of stress, when large amounts of adrenaline (acting at both beta 1-
      and beta 2-adrenoceptors with the same affinity) are released from the adrenal
      medulla, activation of cardiac beta 2-adrenoceptors may contribute to an
      additional increase in heart rate and/or contractility. In chronic heart failure,
      cardiac beta-adrenoceptor function decreases (presumably due to endogenous
      "downregulation" by the elevated catecholamines) and this decrease is related to
      the severity of the disease (judged clinically by NYHA functional
      class).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363263
TI  - Neural transplantation and recovery of function: animal studies.

PMID- 1363264
TI  - [Advantages and disadvantages of the medical treatment of Zollinger-Ellison
      syndrome].

PMID- 1363265
TI  - [Gastrinoma and MEN I].

PMID- 1363266
TI  - Report on the New Zealand College of Midwives 2nd National Midwives Conference.
      'Continuity Choice and Challenge' held in Wellington 28-30 August 1992.

PMID- 1363268
TI  - The Victoria Declaration: implications for nursing research.

PMID- 1363269
TI  - Historical perspective on renin system blockade in the treatment of hypertension.

PMID- 1363270
TI  - Immunoreactivity of an antibody to a beta/A4 sequence with Alzheimer paired
      helical filaments and tau protein.
AB  - beta/A4, a peptide that forms the extracellular amyloid fibrils of Alzheimer
      senile plaques, has also been proposed to be a component of Alzheimer paired
      helical filaments (PHFs). We compared BR88, an antiserum to amino acids 1-12 of
      beta/A4, with BR126, an antiserum to the sequence SEKLDFKDRVQS in tau protein,
      since tau protein is the only confirmed component of PHFs. In enzyme-linked
      immunosorbent assays (ELISAs), both antibodies reacted with pronase-treated PHFs
      better after PHFs were treated with guanidine. tau protein shares no sequence
      homology with beta/A4. Nevertheless, BR88 cross-reacted with human recombinant
      tau isoforms by ELISA and Western blot analysis with potencies comparable to
      those for anti-tau antibodies. BR88 reacted with a beta/A4 peptide as well on a
      molar basis as with tau protein and showed some reactivity to the tubulin-binding
      region of tau protein. In conclusion, the beta/A4 antiserum BR88 cross-reacts
      with tau protein, possibly explaining its reactivity with PHFs.

PMID- 1363267
TI  - Mapping quantitative trait loci for behavioral traits in the mouse.
AB  - After many years of studying various behavioral characters in the mouse, it is
      clear that most are heritable and are specified by complexes of genes or
      quantitative trait loci (QTLs). In order to attain a more complete understanding
      of the genetic causes of individual differences in behavior, the mechanism of
      action of these QTLs must be elucidated. The most straightforward approach to
      determining the mechanism of action of a particular QTL is to identify and
      molecularly clone the gene; this can be done by positional cloning, which depends
      on precise knowledge of the genetic map position. As the genetic data base for
      the mouse genome continues to develop, such strategies will become increasingly
      easy to perform. Here we suggest a multistage strategy for QTL mapping using
      recombinant-inbred strains of mice: (1) characterize genomic DNA from parental
      strains originally used to generate the RI strains; (2) characterize the RI
      strains for a quantitative character and for DNA markers that differ in the
      parental strains; and (3) assess the quantitative character in F2 mice derived
      from crosses between the parental strains, then determine the genotypes of
      extreme F2 mice for markers that account for at least 5% of the additive genetic
      variance. Data from these F2 crosses can be used to test hypotheses from the
      analysis of RI strains, i.e., that a QTL maps to a particular region. Using data
      from the mouse genome data base, this strategy should allow the molecular
      identification of the gene based on a candidate-gene approach. We illustrate the
      approach with examples from our work in mapping QTLs specifying neural
      sensitivity to the anesthetic effects of ethanol.

PMID- 1363271
TI  - Beta-blockers, calcium channel blockers and the sulfhydryl-ACE inhibitors
      demonstrate protection against free-radical-mediated injury of cardiovascular
      cells and membranes.
AB  - During reperfusion of previously ischemic cardiac tissue, oxygen-centered free
      radicals are generated and may result in peroxidative injury of cardiovascular
      cells and membranes. Since the occurrence of reperfusion injury in patients is
      unpredictable, particularly in those patients with chronic ischemic coronary
      artery disease, silent ischemia and those predisposed to significant coronary
      spasm, it would be advantageous to provide continuing therapy with antioxidant
      agents.

PMID- 1363272
TI  - 3-D Microanatomy of Cells and Tissues by SEM. Proceedings of the Xth
      International Symposium on Morphological Sciences. Toronto, Canada, July 1-5,
      1991.

PMID- 1363273
TI  - Cytotoxic drug resistance: molecular basis and clinical significance.

PMID- 1363274
TI  - Establishment of cytotoxic CD4+ T cell clones from cancer patients treated by
      local immunotherapy.
AB  - We have previously reported that the antitumor effect of OK-432, a Streptococcal
      preparation, is markedly augmented when injected intratumorally together with
      fibrinogen (Cancer, 69: 636-642, 1992). In order to elucidate the mechanism of
      the antitumor effects, we established T cell clones from regional lymph nodes of
      colorectal cancer patients who received this local immunotherapy. By culture of
      lymph node lymphocytes, in the presence of IL-2 and OK-432, 4 clones of T cells
      were established from 4 patients treated by local immunotherapy. These clones had
      a helper T cell phenotype (CD3+, CD4+, CD8-, CD56-, WT31+) and were successfully
      maintained for several months. The cells strongly expressed CD25 when stimulated
      with OK-432 and exhibited a high level of cytotoxic activity in part explained by
      the increased expression of ICAM-1 and LFA-1, and the release of TNF beta. These
      results suggest that the CD4+ T cells play a role in the antitumor mechanism of
      local immunotherapy.

PMID- 1363275
TI  - Pharmacological control of gastric acid secretion: molecular and cellular
      aspects.

PMID- 1363276
TI  - [The effect of adrenoblockers on the neurons of the lateral hypothalamus under
      the action of pentagastrin].
AB  - To test the hypothesis of interaction pentagastrin (PG) noradrenaline (NA) in
      central neurochemical mechanisms of food motivation, we studied the activity of
      single neurons in lateral hypothalamus (LH) after s.c. PG injection. Following PG
      injection microiontophoresis (MIF) of propranolol prazosin was made. PG-induced
      changes were similar to neuronal activity in rabbits LH after 24-hour food
      deprivation in 59%. Propranolol-induced changes were following firing pattern in
      the process of food uptake in 68%. Prazosin MIF induced firing pattern of
      neuronal activity of saturated rabbits in 60%.

PMID- 1363277
TI  - [Stress-inducing behavioral changes and the functions of the neurohormonal
      systems in monkeys of different social ranks].
AB  - As a result of intensive stressful stimuli hamadryas baboons developed, depending
      on their hierarchic status, depression-like states varying in severity. Their
      development correlated with a drastic release of biogenic amines, activation of
      pituitary-adrenal system and inhibition of hormonal function of the gonads. It is
      shown that dominant and low-rank monkeys, in spite of the differences in their
      initial psychoemotional states and in the blood levels of mediators and hormones,
      demonstrated marked disintegration in their individual and social behavior. There
      was a larger increase in the blood concentrations of dopamine, serotonin and
      cortisol and more significant inhibition of testosterone production under the
      influence of two-hour immobilization as compared to the subdominant animals.

PMID- 1363278
TI  - [An analysis of the ionic regulation of the specific binding of 3H-diazepam
      depending on the phenotype of the emotional stress reaction].
AB  - It was shown that low NaCl concentrations (less than 50 mM) had more pronounced
      stimulatory effect on [3H]-diazepam ([3H]-DZ) binding in brain membranes of
      Balb/c (C) mice than in C57B1/6 (B6) mice. These interstrain differences
      disappeared after emotional stress in "open field" (OF) test. Low doses of
      diazepam (0.75 mg/kg) and hydazepam (1 mg/kg) induced anxiolytic effect in C mice
      and restored their normal [3H]-DZ binding level in the presence of NaCl. On the
      opposite, effects of the same doses of the benzodiazepines were not revealed
      either on the behavior in OF test or on stimulating properties of NaCl in B6
      mice. Both benzodiazepines (10 mg/kg) induced similar behavior (sedative) and
      receptor (decrease of NaCl stimulating ability) in B6 and C mice. We made a
      conclusion that the ability of NaCl to increase [3H]-DZ binding is a
      physiological index which reflects hereditary differences in emotional-stress
      reactions and behavioral effects of benzodiazepine tranquillizers.

PMID- 1363279
TI  - [The potential-dependent action of the opioid peptide dermorphin].
AB  - Dermorphin action was studied on cross-section strip of frog stomach muscle by a
      mechanographic recorder. The results show that dermorphin (10(-5)-10(-8) M)
      blocks acetylcholine effects, spontaneous activity and muscle contractions
      induced by direct electrical stimulation. All the above effects are hardly
      reversible. Dermorphin fails to block spontaneous and evoked activities if it is
      injected into the incubated medium during K(+)-depolarization (KCI--100 mM) of
      the muscle. Thus, dermorphin has voltage-dependent action. The discussion deals
      with dermorphin action on voltage-dependent Ca(2+)-channels of muscle cell
      membrane.

PMID- 1363280
TI  - Takayasu's aortitis with renovascular hypertension.
AB  - We report a case of Takayasu's disease with severe renovascular hypertension in a
      girl from Eritrea. In the "burn-out" phase after the erythrocyte sedimentation
      rate had normalized, reconstructive vascular surgery was performed as further
      progression of the disease seemed unlikely. However, probably due to her growth,
      the graft rotated and a second operation was successfully performed.

PMID- 1363281
TI  - Management of dental injuries.
AB  - Dental-related injuries, which range from chipped teeth to fractured jaws, are
      among the most common injuries seen in schools. This article describes the
      various injuries and provides guidelines, for the nurse's actions at the scene,
      to ensure the greatest potential for successful treatment. Guidelines are also
      given for informing other school and associated health personnel about dental
      emergencies.

PMID- 1363282
TI  - PC-10 antibody to proliferating cell nuclear antigen (PCNA) is not related to
      prognosis in human breast carcinoma.
AB  - The PC-10 monoclonal antibody to PCNA was employed to analyze proliferative grade
      in conventionally-formalin fixed, paraffin-embedded tumour samples of 162
      patients with primary breast carcinoma. To perform the immunocytochemical method,
      sections were not heated, were de-waxed using alcohol, and then immersed in a
      phosphate-buffered saline solution and in methanol with 0.5% hydrogen peroxide to
      block endogenous peroxidase activity. Immunostaining was performed by a
      streptavidin-biotin peroxidase substrate. A semiquantitative scoring system was
      used to evaluate the fraction of nuclei that were PCNA-positive. The score ranged
      from 0% to 75% with a median value of 25%, mean of 27.8 +/- 1.5. PCNA staining
      was significantly associated with oestrogen receptor-negativity (p = 0.011) and
      correlated, but not at a statistically significant level, with tumour size (p =
      0.08). No significant association was observed between PCNA and node status,
      grading, DNA ploidy, progesterone receptor or menopausal status. Prognostic
      indices such as number of positive lymph nodes and DNA ploidy were significantly
      associated with relapse-free survival (RFS) and overall survival (OS). No
      significant correlation between PCNA nuclear immunostaining and RFS or OS was
      observed after a median follow-up of 4 years. Our results indicate that analysis
      of PCNA alone does not seem to be a useful marker in identifying patients at
      different prognosis in human breast cancer.

PMID- 1363283
TI  - Multidrug resistance (MDR) gene expression in acute non lymphoblastic leukemia:
      sequential analysis.
AB  - Sequential evaluation of P-glycoprotein expression was performed in 29 patients
      with acute nonlymphoblastic leukemia using immunocytochemistry with the C219
      antibody. At diagnosis, 32% of the patients exhibited more than 5% of the P-gp(+)
      leukemic cells. Under chemotherapy, 62% of the patients eventually expressed a
      subset of P-gp positive leukemic cells. After conventional doses of cytosine
      arabinoside (Ara-C) and daunorubicin or mitoxantrone, positive P-gp cells were
      noted in 65% of the cases. This percentage was significantly higher (p = 0.002)
      than the proportion of positive cases (15%) observed after regimens containing
      either intermediate doses of Ara-C or cyclosporine A, a P-gp modulator.

PMID- 1363284
TI  - Angiotensin II actions in paraventricular nucleus: functional evidence for
      neurotransmitter role in efferents originating in subfornical organ.
AB  - Angiotensin II (ANG) has been suggested to be the neurotransmitter utilised by
      subfornical organ (SFO) efferents projecting to the paraventricular nucleus
      (PVN). The PVN has been shown to be involved in mediating the cardiovascular
      response elicited by electrical stimulation of SFO. The possible role of ANG as a
      neurotransmitter in these pathways has been examined in the present study. The
      cardiovascular effects of ANG microinjection into the PVN were examined in
      urethane anaesthetized, male Sprague-Dawley rats. Microinjection of 20 ng or 50
      ng ANG into PVN resulted in mean increases in blood pressure of 12.8 +/- 0.6 mmHg
      (P < 0.0005), and 16.2 +/- 1.4 mmHg (P < 0.0001) respectively, without effect on
      heart rate. These responses were significantly attenuated following systemic
      administration of losartan, an ANG type 1 receptor (AT1) antagonist (Control,
      +12.8 +/- 0.6 mmHg; post-losartan, +5.6 +/- 1.7 mmHg), but were unaffected by the
      AT2 receptor antagonist, PD123319 (Control, +10.8 +/- 1.6 mmHg; post-PD123319,
      +11.6 +/- 2.4 mmHg). Initial and later components of the biphasic pressor
      response elicited by electrical stimulation of SFO (200 microA, 10 Hz, 1 ms pulse
      width, 10 s) were also significantly attenuated by losartan, but unaffected by
      PD123319. The short latency increase in mean arterial pressure was 16.6 +/- 2.3
      mmHg in comparison to a post-losartan increase of 9.3 +/- 1.6 mmHg (P < 0.001).
      Similarly, the secondary response consisted of a control increase of 9.6 +/- 1.3
      mmHg and a post-losartan increase of 3.4 +/- 0.9 mmHg (P < 0.001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1363285
TI  - The effects of selective glutamate receptor antagonists on synchronized firing
      bursts in layer III of rat visual cortex.
AB  - In the rat visual cortex in vitro, single-shock stimulations applied to the
      border between layer VI and the white matter evoke synchronized burst-firing by
      units in layer III. We have examined the effects of glutamate receptor
      antagonists on this activity, with antagonists applied via the bath to allow
      correlation of effects with concentrations. All synaptically driven components
      (recorded extracellularly as field potential 'S2' spikes, dipoles 'W1' and 'W2',
      and coinciding single-unit spikes) were inhibited by greater than 90% in 1.0 mM
      kynurenic acid and in 3 or 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX,
      which selectively blocks AMPA/kainate receptors). S2 spike amplitudes were
      reduced by half in 0.7 microM CNQX. 2-Amino-5-phosphonovalerate (APV), a specific
      blocker of NMDA receptors, did not prevent S2 spike burst or horizontal spread of
      bursting within layer III. However, APV reduced the duration of synchronized
      bursts and the slower potentials which followed. In Mg(2+)-free medium, new
      components appeared which were APV-sensitive: (1) low amplitude spikes,
      distributed spatially like S2 spike, but recurring more slowly, and (2) slow
      potentials, distributed spatially like W1 and W2 potentials, but lasting for
      hundreds of milliseconds. The amplitudes of these spikes were reduced by half in
      3 microM D-APV. Our data imply that: (1) glutamate receptors play a major role in
      mediating local, excitatory neurotransmission in the supragranular layers of
      neocortex, with NMDA and AMPA/kainate subtypes each subserving somewhat different
      functions; (2) AMPA/kainate receptors mediate rapid excitatory transmission
      between layer III neurons, responsible for driving the first 15 ms of
      synchronized bursts; (3) currents gated by NMDA receptors determine the duration
      of coherent firing bursts, and drive asynchronous neuronal firing following
      bursts; and (4) under conditions which circumvent block by extracellular Mg2+,
      activation of NMDA receptors greatly enhances and prolongs the response to single
      shock stimulations. In vivo, activation of layer III neurons is likely to depend
      significantly upon currents gated by NMDA receptors whenever repetitively firing
      excitatory inputs summed over several tens of milliseconds provide enough
      depolarization to lift block by extracellular Mg2+.

PMID- 1363287
TI  - Role of cervical neurons in propriospinal inhibition of thoracic dorsal horn
      neurons.
AB  - We previously reported that electrical or glutamate stimulation of the cervical
      spinal cord elicits a 40-60% decrease in renal sympathetic nerve activity (RSA)
      in the anesthetized rats. This sympatho-inhibition was possible, however, only
      after transection of the spinal cord at C1 or GABAergic inhibition of neurons in
      the rostral ventrolateral medulla. We postulated that cervical neurons inhibit
      RSA by inhibiting the activity of spinal interneurons that are antecedent to
      sympathetic preganglionic neurons (SPNs), and that these interneurons may be, in
      turn, excited by afferent signals. In this study, we tested the hypothesis that
      cervical neurons can inhibit visceroceptive thoracic spinal neurons. We recorded
      the spontaneous and evoked activity of 45 dorsal horn neurons responsive to
      splanchnic stimulation before, during, and after chemical or electrical
      stimulation of the cervical spinal cord in chloralose-anesthetized spinal rats.
      Cervical spinal stimulation that inhibited RSA also inhibited the spontaneous
      and/or evoked activity of 44 dorsal horn neurons. In addition to inhibiting
      splanchnic-evoked neuronal responses, cervical stimulation also inhibited
      responses, in the same neurons, evoked by noxious heat or light brushing of
      receptive dermatomes. We concluded that cervical neurons participate in
      propriospinal inhibition of afferent transmission and that this inhibitory system
      may be involved in controlling the access of afferent information to SPNs.

PMID- 1363286
TI  - Interaction between medullary and cervical regulation of renal sympathetic
      activity.
AB  - We have reported that electrical or glutamate stimulation of the dorsolateral
      surface of the cervical spinal cord elicits a 40-60% decrease in renal
      sympathetic activity (RSA) in anesthetized rats. Because evoked sympatho
      inhibition was observed, however, only after transection of the cervical spinal
      cord at C1, we suggested that unidentified supraspinal neurons affect the
      regulation of RSA by cervical neurons. In the present experiments, we tested the
      hypothesis that the modulatory supraspinal neurons are located in the
      ventrolateral medulla by observing the effects of rostroventral, lateral,
      medullary (RVLM) injections of the GABAergic agonist, muscimol, on baseline RSA
      and on our ability to inhibit that activity by cervical stimulation. GABAergic
      inhibition in the RVLM of chlorolose anesthetized rats elicited changes in RSA
      that were similar to those observed after transection of the spinal cord,
      including a 41% decrease in mean arterial pressure and a 44% increase in RSA.
      Moreover, after muscimol inhibition of RVLM neurons, electrical or glutamate
      stimulation of the dorsolateral cervical spinal cord elicited a decrease in RSA
      in otherwise intact rats. These results suggest that neurons in the RVLM interact
      with neurons in the cervical spinal cord in the regulation of RSA.

PMID- 1363288
TI  - Disruption of synaptosomal calcium channel function by Lambert-Eaton myasthenic
      immunoglobulin is serum-dependent.
AB  - An autoantibody to nerve terminal Ca2+ channels has been suggested to mediate the
      pathogenesis of the neuromuscular disorder Lambert-Eaton Myasthenic Syndrome
      (LEMS). We demonstrated previously that in the presence of control human serum,
      immunoglobulins isolated from a patient with LEMS reduced flux of Ca2+ into
      isolated nerve terminals during depolarization. The objective of the present
      study was to determine the role of serum in reducing uptake of 45Ca2+ into rat
      brain synaptosomes by LEMS IgG. Depolarization-dependent uptake of 45Ca2+ through
      voltage-gated Ca2+ channels was determined using synaptosomes incubated with
      control (disease-free) and LEMS IgG with or without control human serum. In the
      absence of human serum, LEMS IgG did not reduce uptake of 45Ca2+ into
      synaptosomes. However, in the presence of control human serum (10% of total
      incubation volume), 45Ca2+ uptake was reduced significantly by LEMS IgG (2 and 4
      mg/ml), but not by IgG from disease-free patients or by 10% (v/v) control human
      serum alone. This concentration of serum was found to be optimal; higher
      concentrations produced significant reductions in Ca2+ uptake, whereas at lower
      concentrations the serum/IgG combination was ineffective. The depressant effect
      of high concentrations of serum alone on 45Ca2+ uptake was mimicked by equal
      concentrations of bovine serum albumin suggesting that deficits in 45Ca2+ uptake
      produced by high concentrations of serum were due to increased protein binding of
      the radiolabel. Heat-inactivating the serum abolished its ability to interact
      with the LEMS immunoglobulins to depress 45Ca2+ uptake. This suggested a role for
      complement in this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363290
TI  - World conference update.

PMID- 1363289
TI  - Specificity of Lambert-Eaton myasthenic syndrome immunoglobulin for nerve
      terminal calcium channels.
AB  - Lambert-Eaton Myasthenic Syndrome (LEMS) is a presynaptic, neuromuscular disorder
      characterized by impaired nerve-evoked release of ACh. Repetitive nerve
      stimulation, which increases the probability of quantal release, improves the
      transmission defect. An autoantibody to Ca2+ channels of presynaptic motor nerve
      terminals is thought to mediate the pathogenesis of this disease. The goal of the
      present study was to examine the specificity of LEMS autoantibodies for nerve
      terminal Ca2+ channels as compared to other voltage-sensitive ion channels in
      nerve terminals, and to determine if non-specific membrane damage contributed to
      the pathogenesis of LEMS. The ion channel specificity of LEMS autoantibody was
      assessed by comparing the ability of acute application of IgG isolated from the
      plasma of a patient with LEMS to reduce depolarization-dependent uptake of 45Ca2+
      and 22Na+ into or efflux of 86Rb+ from rat forebrain synaptosomes. The clinical
      diagnosis of LEMS was confirmed electrophysiologically by treatment of mice for
      30 days with plasma (1.5 ml/day) taken from this patient. Characteristic
      reduction of quantal content elicited at 1 Hz and facilitation at 20 Hz was
      observed in mice treated with LEMS plasma compared to those treated with control
      plasma. One s, K(+)-stimulated 45Ca2+ uptake was inhibited 36.5 +/- 14.5% and
      44.5 +/- 9.8% by acute application of 2 and 4 mg/ml LEMS IgG, respectively; IgG
      from patients with small cell carcinoma of the lung (SCC) had no effect on 45Ca2+
      entry. The same concentrations of LEMS IgG affected neither voltage-dependent
      uptake of 22Na+ into veratridine-depolarized synaptosomes nor 86Rb+ efflux from
      K(+)-depolarized synaptosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363292
TI  - Treatment of stroke.

PMID- 1363291
TI  - [Pharmacologic profile of dithiadenoxide, a potential non-sedating H1
      antihistaminic].
AB  - Dithiadenoxide, a product of metabolic S-oxidation of the H1-antihistaminic agent
      dithiaden (bisulepin, Dithiaden), is also an effective histaminic H1-antagonist
      in pharmacological experiments in in vivo conditions. In contrast to dithiaden,
      dithiadenoxide exerts a demonstrable inhibitory action as much as the subtoxic or
      sublethal dosage in experiments in mice and rats. Its acute toxicity in mice and
      guinea-pigs substantially decreases; acute toxicological findings in rats are not
      unambiguous. Other experimental findings demonstrate higher selectivity of
      pharmacological effects of dithiadenoxide.

PMID- 1363294
TI  - Receptors for L-glutamate and GABA in the nervous system of an insect
      (Periplaneta americana).
AB  - The nervous system of the cockroach Periplaneta americana is well suited to
      studies of invertebrate amino acid receptors. Using a combination of radioligand
      binding and electrophysiological techniques, several distinct receptors have now
      been identified. These include an L-glutamate-gated chloride channel which has no
      known counterpart in the vertebrate nervous system, and a putative
      kainate/quisqualate receptor with pharmacological properties different from those
      of the existing categories of vertebrate excitatory amino acid receptors. GABA
      receptors have also been characterized in the cockroach nervous system.
      Bicuculline, benzodiazepines and steroids have revealed important differences
      between certain insect GABA-gated chloride channels and vertebrate GABA
      receptors. Identifiable neurones may facilitate the allocation of specific
      functions to amino acid receptor subtypes. In view of the existence of subtypes
      of amino acid receptors in insects, it is of interest to examine how this is
      reflected at the molecular level in terms of receptor subunit composition and
      amino acid sequence. Preliminary molecular cloning studies on insect GABA
      receptors are described.

PMID- 1363293
TI  - Some hazards of diving.

PMID- 1363295
TI  - An initial screen of a series of neuroactive peptides for activity on identified
      central neurones of Helix aspersa.
AB  - 1. Intracellular recordings were made from identified neurones in the
      suboesophageal ganglia of Helix aspersa. Seven neuropeptides were tested for
      activity and their actions compared with acetylcholine and FMRFamide. 2. Three
      peptides isolated from nematodes, AF-1, AF-2 and PAN-1 had mainly inhibitory
      effects with thresholds of around 1 nM. This inhibition was due to an increase in
      potassium conductance. 3. The molluscan neuropeptides LSSFVRIamide, CARP and ACEP
      1 were all active on certain neurones; the first two showed only inhibitory
      effects while ACEP-1 was mainly excitatory. The thresholds in each case were 0.1
      10 microM. When norleucine replaced methionine in CARP, the potency was reduced
      by at least 100 times. 4. The echinoderm peptide, SALMF-1, only excited neurones
      but with a very low threshold, around 1.0 fM. 5. There was no obvious correlation
      between the action of these peptides and either acetylcholine or FMRFamide.

PMID- 1363296
TI  - Inhibition of programmed cell death by cyclosporin.
AB  - 1. Apoptosis is generally believed to occur as a consequence of activation of an
      internal, genetically controlled, program in the dying cells. 2. We have proposed
      an alternative hypothesis that, in hormone-induced apoptosis, the active
      participation of dying cells in the death process may be limited to expressing
      surface proteins that permit identification of cells destined to die by cytotoxic
      effector cells. 3. We investigated the effects of the immunosuppressant,
      cyclosporin, and the lysosomotropic agents, chloroquine and N-ethyl maleimide on
      thyroid hormone-induced regression of the bullfrog tadpole tail. 4. All three
      substances blocked regression. These results suggest that patency of the
      intracellular protein trafficking machinery is essential for programmed cell
      death in our system.

PMID- 1363297
TI  - The effects of m-octopamine on salivary flow rates and protein secretion by rat
      submandibular glands.
AB  - 1. m-Octopamine given i.v. or i.p. was a potent sialogogue for rat salivary
      glands. 2. Salivation in response to i.v. m-octopamine was completely abolished
      by prazosin and phenoxybenzamine. 3. The alpha-type of proteins were secreted in
      response to all doses of i.v. and i.p. m-octopamine and these were converted into
      the beta-type with prazosin, but not with yohimbine. 4. m-Octopamine stimulated
      both alpha- and beta-adrenoceptors and was a much more selective alpha 1-agonist
      than was the p-isomer.

PMID- 1363298
TI  - Cardiac activity of some peptide hormones in the frog, Rana tigrina.
AB  - 1. The cardiac responses of isolated frog (Rana tigrina) atria to peptide
      hormones were studied. 2. Calcitonin gene-related peptide (CGRP), arginine
      vasotocin (AVT), bovine parathyroid hormone fragment (bPTH-(1-34)) and oxytocin
      (OXY) produced dose-related positive chronotropic and inotropic responses; atrial
      natriuretic peptide (ANP) was negative chronotropic and inotropic;
      cholecystokinin (CCK), vasoactive intestinal peptide (VIP) were without effects.
      3. The dose-related responses under bPTH-(1-34) stimulation but not CGRP or AVT
      were attenuated in the presence of ANP (300 ng/ml, approximately 0.98 x 10(-7)
      M). As expected ANP decreased the basal AR and AT responses of the isolated atria
      and the inhibitory effects were dose-dependent. 4. As shown previously,
      propranolol blocked the atrial tension stimulated by bPTH (1-34) but did not
      alter the cardiac responses to CGRP and AVT. 5. In the presence of beta
      adrenergic blocker (propranolol 10(-7) M) or ANP (10(-7) M), the AR and AT
      changes under ISO stimulation in the frog were also decreased. 6. These cardiac
      changes suggest the cardiac inhibitory effects of ANP are related to beta
      adrenoceptor activity and ANP might be a beta antagonist.

PMID- 1363299
TI  - Effects on rat renal osmolytes of extended treatment with an aldose reductase
      inhibitor.
AB  - 1. The mammalian renal medulla uses sorbitol, myo-inositol, betaine and
      glycerophosphorylcholine as intracellular osmolytes. 2. Sorbitol synthesis was
      inhibited by feeding male Wistar rats the aldose reductase inhibitor sorbinil at
      40 mg/kg/day for 71 d, and renal inner medullas were extracted for analysis. 3.
      Aldose reductase activities and sorbitol contents were greatly reduced in
      sorbinil-treated animals, while betaine contents increased significantly (with no
      other osmolytes changing). 4. The betaine increase compensated for the sorbitol
      decrease such that the total organic osmolytes maintained the same ratio to
      sodium contents as controls. 5. These results are identical to the pattern
      previously reported for sorbinil treatment of rats for 10 d, but not for 21 d.

PMID- 1363300
TI  - Adenylate cyclase from Hirudo medicinalis segmental ganglia: modulation by
      physiological and non-physiological agents.
AB  - 1. In Hirudo medicinalis segmental ganglia GTP is essential for the full
      expression of the stimulatory action of serotonin on the adenylate cyclase
      activity. The amine, in turn, increases the overall affinity of the enzymatic
      system for GTP. 2. GTP gamma S and Gpp(NH)p, non-hydrolysable analogues of GTP,
      dose-dependently enhance the basal enzyme activity, but impair the stimulatory
      effect of serotonin. 3. Fluoride ions biphasically modulate the leech adenylate
      cyclase both in the absence and in the presence of GTP. The ion effect is also
      influenced by non-physiological guanine nucleotides.

PMID- 1363302
TI  - Adenosine-theophylline interactions on the lipolytic response to beta-adrenergic
      agonists in porcine adipose tissue.
AB  - 1. Many beta-adrenergic agonists did not stimulate porcine adipose tissue slice
      lipolysis unless theophylline, an antagonist of the adenosine receptor was added
      to the incubation medium. 2. In contrast to previous results, theophylline itself
      was an effective lipolytic agonist in tissue from many pigs. 3. Lipolysis was
      partially inhibited by adenosine or phenylisopropyl adenosine. Lipolysis was
      marginally stimulated by adenosine deaminase or 8-phenyltheophylline. 4. The data
      suggest that the mechanism of theophylline stimulation of lipolysis was only
      partially through antagonism of the adenosine receptor.

PMID- 1363301
TI  - Responses of the rectum and oesophagus of the snail Helix aspersa to purine
      nucleotides and nucleosides.
AB  - 1. Purine compounds were examined for pharmacological activity in the rectum and
      oesophagus of the garden snail Helix aspersa. 2. In the rectum, adenosine, AMP,
      ADP and ATP (above 10 microM) and acetylcholine (above 1 nM) consistently caused
      concentration-dependent contractions. The slope of the dose-response curve for
      ADP in the rectum was significantly steeper than for the other purine compounds.
      The contractile responses to the nucleotides and acetylcholine, but not
      adenosine, were selectively potentiated by physostigmine (1 microM). Atropine (1
      microM) and tubocurarine (30 microM) failed to block the responses to the purines
      or acetylcholine. 3. In the oesophagus, adenosine, AMP, ADP and ATP (above 10
      microM) and acetylcholine (above 1 nM) caused concentration-dependent
      contractions that were antagonised by atropine (1 microM). Tubocurarine (30
      microM) failed to block the responses to the purine compounds or acetylcholine.
      Physostigmine (1 microM) potentiated the responses to ADP and acetylcholine but
      not ATP, AMP or adenosine. 4. In both the rectum and the oesophagus, the
      synthetic analogues of purine compounds including 2-chloroadenosine, alpha,beta
      methylene ATP and 2-methylthio ATP were inactive up to a concentration of 100
      microM. 5. Electrical field stimulation of the rectum and oesophagus produced
      consistent contractions which were unaffected by atropine (1 microM),
      tubocurarine (30 microM) or physostigmine (1 microM). These responses were not
      modulated by any of the purine compounds or their stable analogues. 6. The
      responses obtained appear novel even within known invertebrate purinergic
      systems, suggesting a differentiation of purinoceptor subtypes in this
      species.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363303
TI  - Inhibition of slow TTX-insensitive inward current by the anticonvulsant
      carbamazepine in an identified neuron of Lymnaea stagnalis.
AB  - 1. Pentylenetetrazol (PTZ), induces tonic depolarization and bursting activity in
      an identified neuron, B1, of Lymnaea stagnalis. This is due in part to activation
      of a slow, tetrodotoxin-insensitive inward sodium current. 2. Carbamazepine (CBZ)
      reversed the effect of PTZ on both membrane potential and inward current, after a
      delay of up to 5 min. CBZ alone had no effect on voltage or current responses. 3.
      These results suggest that CBZ blocks the slow sodium current, possibly via a
      decrease in intracellularly stored calcium ions.

PMID- 1363304
TI  - Alterations in rat alveolar surfactant system induced by treatment with carbicron
      (O-[(2-butenoic acid)-N,N-dimethylamide-3-yl]-O,O-dimethylphosphate).
AB  - 1. Intoxication of rats with carbicron (O-([2-butenoic acid)-N,N-dimethylamide-3
      yl]-O,O-dimethylphosphate) induced a reduction of the total phospholipids and
      phosphatidylcholine in lung alveolar surfactant. 2. The lipid transfer protein
      activity was inhibited due to carbicron treatment. 3. No alterations were
      observed in phospholipase A2 activity in the alveolar surfactant of intoxicated
      animals. The structural order parameter (SDPH) of bilayer liposomes, prepared
      from surfactant phospholipids of carbicron-treated rats also remained unchanged.

PMID- 1363305
TI  - Effect of temperature reduction on the reactivity of the mouse vas deferens to
      adrenergic drugs.
AB  - 1. Dose-response curves for noradrenaline, phenylephrine and clonidine were
      determined isometrically on the mouse vas deferens at 26 degrees C, 15 degrees C
      and compared to the one obtained at 37 degrees C. 2. In the presence of
      noradrenaline, reducing temperature induced an increase of both maximal developed
      tension and sensitivity to the drug. Reduction by 50% of the extracellular
      calcium concentration abolished the maximal contraction potentiation. 3. When
      reducing temperature to 26 degrees C, the maximal contraction was increased and
      depressed in the presence of phenylephrine and clonidine respectively. 4. The
      results suggest (a) that cooling increases the reactivity of mouse vas deferens
      by activation of alpha 1 adrenoceptors and depresses it by activation of alpha 2
      adrenoceptors (b) that calcium ions could play an important role in the
      potentiation of the maximal contraction.

PMID- 1363306
TI  - Feeding behavior and brain acetylcholinesterase activity in bream (Abramis brama
      L.) as affected by DDVP, an organophosphorus insecticide.
AB  - 1. Bream (Abramis brama) were exposed to sublethal concentration of
      organophosphorus insecticide DDVP and the amount of food consumed and brain
      acetylcholinesterase (AChE) examined in exposed fish. 2. Exposure to DDVP
      resulted in decreased amount of food consumed and inhibited brain AChE activity.
      3. Intraperitoneal injection of the fish with cholinergic drugs, atropine and TMB
      4 recovered the feeding efficiency in exposed fish. TMB-4 recovered brain AChE
      activity as well. 4. The results revealed that cholinergic system in fish brain
      constitutes biochemical mechanism controlling feeding behavior in fish.

PMID- 1363307
TI  - The effect of mercury on chloride secretion in the shark (Squalus acanthias)
      rectal gland.
AB  - 1. Mercuric chloride inhibited chloride secretion in a dose dependent way in
      isolated perfused rectal glands. The effect was readily apparent at a
      concentration of 10(-6) M and profound and irreversible at 10(-4) M. 2. The
      dithiol dithiothreitol (DTT) 10(-2) M completely prevented the effect of 10(-6) M
      mercuric chloride, reduced that at 10(-5) M and 10(-4) M, and made the inhibition
      at the latter concentration reversible. 3. Two organic mercurials, mersalyl and
      meralluride, that are effective diuretics in the mammalian kidney, and p
      chloromercuribenzoyl sulfonic acid (PCMBS), that has no diuretic activity, had no
      effect on chloride secretion by the rectal gland. 4. The effect of mersalyl was
      not modified by lowering the pH of the solution perfusing the glands. 5. These
      results indicate that inorganic mercury and organic mercurials do not share the
      same mechanism of action. 6. The absence of an effect of organic mercurials on
      chloride transport in the rectal gland suggests that its effect on another
      chloride transporting epithelia, the thick ascending limb of the loop of Henle,
      is not mediated by inhibition of the chloride cotransporter or Na+, K(+)-ATPase,
      common to both epithelia.

PMID- 1363308
TI  - Accumulation and excretion of aluminium and iron by the terrestrial snail Helix
      aspersa.
AB  - 1. The snail Helix aspersa was fed one 24 hr meal containing Al, Fe or both
      together in barley flour pellets. Accumulation and distribution within the
      digestive gland, kidney, crop and remaining soft tissues were examined over the
      subsequent 30 days using atomic absorption spectroscopy (A.A.S.). 2. The
      digestive gland contained significantly (P < 0.05) elevated levels of Al and Fe
      for 8 and 12 days. The digestive gland is the major sink for both Al and Fe in
      Helix. 3. The kidney rapidly accumulated Al and Fe but the increase was short
      lived. The kidney may therefore be involved in the elimination of metal not
      incorporated into the digestive gland. 4. Iron was absorbed by the crop but Al
      was not. This may indicate a route of uptake of Fe into the digestive gland not
      shared with Al. 5. No obvious pattern of accumulation of Al and Fe were seen in
      the remaining soft tissues or the blood of Helix. 6. Aluminium is present in the
      faeces for 12 days suggesting that Al is released relatively slowly. 7. Presence
      of both Al and Fe in the feed induced a change in the pattern of accumulation in
      the digestive gland but not in the kidney, crop and remaining soft tissues. 8.
      The distribution of Al is discussed in relation to the suggestion that Al follows
      the ferretin pathway during accumulation.

PMID- 1363309
TI  - Some effects of aluminium on rat brain protein synthesis.
AB  - 1. Infant rats and rabbits received intraperitonal aluminium (Al) chloride (5, 10
      or 20 mg Al/kg body weight) every third day from one to four weeks of age. 2.
      When the polysomal fraction was tested in a protein synthesizing system, a
      significant increase in the incorporation of [14C] leucine, [14C] phenylalanine,
      or [35S] methionine into proteins in vitro was observed at the higher doses in
      rats but not rabbits. 3. The incorporation of [35S]methionine into brain ferritin
      was measured using polysomal mRNA or mRNA "stored" in the ribonucleoprotein (RNP)
      particle fraction. 4. The results suggest that Al exposure causes the
      mobilization of ferritin mRNA from the latter fraction to the polysomal fraction
      for increased ferritin synthesis.

PMID- 1363310
TI  - Potentiation by m-cresol on transepithelial sodium transport across frog skin
      induced by insulin.
AB  - 1. In this study we found that insulin mixed with m-cresol, normally used as
      pharmaceutical preparation, shows an earlier and larger stimulating effect on
      transepithelial sodium transport than insulin alone. 2. The action displayed by
      the m-cresol seems to be specific for insulin because m-cresol mixed with ADH, a
      hormone known to stimulate sodium transport, failed to show the potentiation seen
      for insulin. 3. It is proposed that m-cresol could facilitate the interaction
      with its receptor by modifying the insulin molecule. 4. This finding could be of
      biological and pharmacological importance.

PMID- 1363312
TI  - Current status of medical treatment of tachyarrhythmias.

PMID- 1363311
TI  - Characteristics of outward current induced by application of dopamine on a snail
      neuron.
AB  - 1. A closer characterization of the potassium channel opened by the application
      of dopamine (DA) on an identified Helix pomatia neuron was attempted. The effect
      of K+ channel blockers (TEA and 4-AP) on the DA-induced current was examined. The
      results indicate that the channel opened by DA does not share the pharmacological
      properties of other snail neuron K-channels. 2. The I-V relation for IDA was
      successfully fitted by the Constant Field equation except below the reversal
      potential where the current was smaller than expected. The assumption that DA
      binding is voltage-sensitive is supported by the increment of the Hill
      coefficient with hyperpolarization (from nH approximately equal to 1 to nH
      approximately equal to 2). 3. The presence of the phosphodiesterase inhibitor
      IBMX does not affect the DA induced outward current. However, the assumption that
      the snail neurons' DA receptor belongs to the D2 class is in contrast to the
      antagonistic effects of ergot alkaloids which, in mammalian neurons, are
      competitive antagonists of D1 receptors. 4. The examination of the voltage
      sensitivity of the blocking action of the ergot alkaloid (Bromoergocryptinine)
      revealed that it does not compete with DA for the same binding site as in
      mammalian D1 receptors.

PMID- 1363313
TI  - [Summary of the National Seminar of Dysfunctional Uterine Bleeding].

PMID- 1363315
TI  - [The effect of antipsychotic drugs on dopamine-receptors on caudate calf].
AB  - Using radioligand receptor binding assay (RRA), dopamine receptor in the calf
      caudate were identified with 3H-Spiperone as radioactive ligand. The total number
      of maximal binding sites (Bmax), the equilibrium dissociation affinity (Kd), the
      concentrations of drug required to inhibited 50% specific binding (Ic50) and
      competitive inhibition constant (Ki) of antipsychotics in calf caudate were
      determined by sturative binding experiment and inhibitive binding experiment. The
      result showed the mean Bmax was 0.659 pmol/mg protein membrane and Kd was 0.31
      nmol/L. Scatchard analysis denotes that it was hyperbole and there were two
      binding positions in calf caudte. Antipsychotics can inhibit 3H-Spiperone binding
      specifically the order of affinity constants (1/Ki) was Haloperdol and sulpiride,
      Chlorpromazine and Clozapin, Tranquis and Taractan. This abilities of drugs to
      compete with 3H-Spi binding will be used as basis of RRA for measuring blood
      levels of antipsychotics.

PMID- 1363314
TI  - DNA polymerase delta and epsilon holoenzymes from calf thymus.
AB  - Replication of singly-DNA primed M13 DNA by DNA polymerase (pol) delta completely
      relies on the simultaneous addition of proliferating cell nuclear antigen (PCNA),
      replication factor C (RF-C) and replication protein A (RP-A) (or E. coli single
      strand DNA binding protein, SSB). Pol epsilon core alone is able to synthesize
      the products on singly-primed ssDNA. However, DNA synthesis by pol epsilon was
      stimulated up to 10-fold upon addition of the three auxiliary proteins PCNA, RF-C
      and SSB. This stimulation of pol epsilon by PCNA/RF-C/SSB appears to be the
      superposition of two events: pol epsilon holoenzyme (pol epsilon, PCNA, RF-C)
      synthesized longer products than its pol epsilon core counterpart, but elongated
      less primers. Furthermore, we analyzed the cooperative action of pol
      alpha/primase with pol delta or pol epsilon holoenzymes on unprimed M13 DNA.
      While pol delta displayed higher dNMP incorporation than pol epsilon, when a
      single primer was preannealed to DNA, pol epsilon was more efficient in the
      utilization of the primers synthesized by pol alpha/primase. Under these
      conditions both longer products and a higher amount of dNMP incorporation was
      found for pol epsilon holoenzyme, than for pol delta. Our data support the
      hypothesis of pol delta as the leading and pol epsilon as the second lagging
      strand replication enzyme.

PMID- 1363316
TI  - [Pathophysiology and gene abnormalities of endocrine tumors].
AB  - Various functioning and non-functioning tumors arise from endocrine glands in
      both the sporadic and familial forms and pathophysiology of the tumors is
      variable due to differences in the sort of tumor-bearing endocrine organs and in
      the amount of hormones released. In this paper, gene abnormalities in growth
      hormone (GH)-secreting pituitary adenoma, ectopic GHRH-producing tumor, multiple
      endocrine neoplasia (MEN) and ectopic parathyroid hormone (PTH)-producing tumor
      are documented in relation to etiology and pathophysiology. GH-secreting
      pituitary adenoma is heterogeneous in clinical features, pathological findings
      and GH responses to various secretagogues. A point mutation of codon 201 of Gs
      alpha gene was observed in 2 out of 45 GH-secreting pituitary adenomas (4.4%),
      but no point mutation of Gi2 alpha gene was found. Pituitary tumors may occur at
      any stage of differentiation from the totipotent cells to mature anterior
      pituitary cells, and the mutations of Gs alpha and H-ras genes as well as loss of
      heterozygosity (LOH) found on chromosome 11 in some adenomas must be involved in
      their tumorigeneses. Since 1959, 34 patients with ectopic GHRH-producing tumor
      associated with acromegaly have been reported. In our case of MEN type 1, the
      paradoxical rise of plasma GH after TRH or glucose administration disappeared
      after resection of the tumor. The tumor cells showed neither rearrangement nor
      amplification of GHRH gene and 20 oncogenes including ras, myc, and erb. Only
      LOHs of HRAS1 and D11S151 were detected in this tumor, but no point mutation was
      found in HRAS1 gene. Therefore, a kind of tumor suppressor gene may be involved
      in the tumorigenesis of the tumor in addition to inactivation of MEN-1 locus. In
      MEN-1 patients, we reported LOH on chromosomes 1, 9, 11 and 16, while we reported
      point mutation as being present only in Gs alpha gene on chromosome 20. This
      point mutation was found specifically in GH-secreting pituitary adenoma but not
      in hyperplastic parathyroid and pancreas adenoma. These data suggest that in MEN
      1 patients tumorigenesis occurs and advances from hyperplasia and adenoma to
      cancer during multistep changes of genes such as inactivation of MEN-1 gene and
      other tumor suppressor genes and activation of oncogenes. Ectopic PTH-producing
      tumor was first reported by us in 1989, and this was followed by 2 papers. These
      patients showed a disturbance of consciousness and high levels of serum calcium
      and plasma PTH.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1363317
TI  - Fishes of District Sundargarh, Orissa, with special reference to their potential
      in mosquito control.
AB  - An extensive fish fauna survey was carried out in Sundargarh, a malaria-endemic
      district in Orissa, during 1988 to 1990 to identify and evaluate the indigenous
      larvivorous fishes for mosquito control. In all, 57 species belonging to 19
      families under 6 orders were found in the local water bodies. On laboratory
      evaluation against anopheline and culicine larvae, six potential larvivorous
      fishes, viz. Aplocheilus panchax, Oryzias melastigma, Oreochromis mossambicus,
      Gambusia affinis, Danio (B.) rerio and Esomus danricus were selected. Feasibility
      of mass multiplication of these fishes in village ponds for operational use is
      being studied.

PMID- 1363318
TI  - Water mite (Arrenurus sp.) parasitizing mosquitoes in District Shahjahanpur, U.P.

PMID- 1363319
TI  - Search for enteric microbial pathogens in patients with ulcerative colitis.
AB  - Microbial pathogens were sought in faeces of patients with active ulcerative
      colitis and again after 3 months treatment. 64 patients were examined during
      their first episode of ulcerative colitis and 30 with relapse of chronic disease.
      At presentation, bacterial pathogens were not found; 1 patient had
      cryptosporidiosis. In 10 patients treatment appeared to result in some loss of
      colonisation resistance as evidenced by colonisation with beta-haemolytic
      streptococci, Staphylococcus aureus, candida and Clostridium difficile.
      Unidentified cytotoxic activity was present in the faeces of 4 patients at
      presentation and 2 patients during or after treatment. We conclude that enteric
      infection is an uncommon finding in patients with active ulcerative colitis.

PMID- 1363320
TI  - Effect of gastrin receptor antagonists on gastric acid secretion and gastrin and
      somatostatin release in the rat stomach.
AB  - The effects of two recently developed gastrin receptor antagonists, PD 136450 and
      L-365,260, on pentagastrin-stimulated acid secretion were investigated in rats.
      PD 136450 at a dose of 6 mg/kg s.c. (9.6 mumol) completely abolished acid
      secretion induced by pentagastrin. The inhibition of 18 mg/kg PD 136450 s.c.
      lasted for at least 8 h and was still effective after 14 days of treatment (18
      mg/kg s.c. every 8 h). Acute application of L-365,260 at a dose of 3.8 mg/kg,
      which is equimolar (9.6 mumol) to 6 mg/kg PD 136450 reduced acid responses
      slightly. However, when L-365,260 was administered intravenously at a dose of 3
      mg/kg, this antagonist completely abolished the pentagastrin-stimulated acid
      secretion. Furthermore, the effect of PD 136450 on endogenous gastric
      somatostatin and gastrin releases was tested in the isolated, vascularly perfused
      rat stomach. PD 136450 perfused at a concentration of 1 microM slightly increased
      somatostatin secretion after stimulation with a high dose of isoproterenol (10(
      7) M). There was no effect of PD 136450 on basal or acetylcholine-stimulated
      gastrin secretion.

PMID- 1363321
TI  - Effects of progesterone on some brain neurotransmitters in intact rats.
AB  - Effects of progesterone on four neurotransmitters (viz, noradrenaline, 5-HT,
      dopamine and histamine) of brain were seen in rats with intact ovaries. It was
      found that progesterone lowers the noradrenaline concentration in medulla, pons,
      midbrain, hypothalamus, thalami and pituitary, uniformly, when the rats were
      killed within 4 hours of progesterone injection. At longer intervals (48 hrs)
      effects of progesterone were seen when progesterone in heavy dose was
      administered to rats pretreated with estrogen. It is likely that one of the modes
      of action of the oral contraceptives may be the reduction of noradrenaline
      content in selected areas of brain, by progesterone. It is also suggested,
      therapeutic usage of progesterone carries the risk of development of depression
      in the user.

PMID- 1363322
TI  - Development and trends in the drug treatment of essential hypertension.
AB  - AIM: A brief survey is given of the development of the drug therapy of essential
      hypertension over five decades, followed by a discussion on newer
      antihypertensive drugs and principles. DRUGS THAT MODULATE THE SYMPATHETIC
      NERVOUS SYSTEM: Virtually all levels and elements of the sympathetic nervous
      system can be modulated by drugs in such a manner that elevated blood pressure is
      lowered, for instance with the use of central alpha 2-adrenoceptor agonists
      (clonidine, alpha-methyldopa), ganglioplegic drugs, peripheral adrenergic neurone
      blockers, and alpha- and beta-adrenoceptor antagonists. The beta-blockers have
      been maintained as a very major group of antihypertensive therapeutics. Among
      alpha-adrenoceptor antagonists, only the selective alpha 1-blockers are useful as
      antihypertensive drugs, although some interest has developed in newer alpha 2
      adrenoceptor antagonists which are selective for postsynaptic alpha 2
      adrenoceptors. DIURETICS: Diuretics, in spite of some criticism, are still a
      cornerstone in antihypertensive drug treatment. Their position has been
      reinforced by the results of the recent Systolic Hypertension in the Elderly
      Program, Swedish Trial in Old Patients with Hypertension and Medical Research
      Council (Elderly) trials. CALCIUM ANTAGONISTS: Calcium antagonists have been
      extended by several new dihydropyridines which appear to be more vasoselective
      than the classical compounds. ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS:
      Various new ACE inhibitors have been introduced, but so far they have not clearly
      offered major advantages over the established compounds. NEW POTENTIAL
      ANTIHYPERTENSIVE DRUGS: Renin inhibitors and angiotensin II-receptor antagonists
      are being studied for their potential as antihypertensive drugs and they are also
      important because they may modulate the renin-angiotensin-aldosterone system.
      Inhibitors of neutral endopeptidase will cause an accumulation of endogenous
      atrial natriuretic peptide, and hence lower blood pressure by counteracting
      several effects of the renin-angiotensin-system. Potassium channel openers are
      vasodilators and potential antihypertensive drugs with additional anti-ischaemic
      activity.

PMID- 1363324
TI  - Report of the Fifth International Symposium of the Foundation for Promotion of
      Cancer Research--Fundamental and Clinical Research in Pancreatic and Biliary
      Tract Cancers.

PMID- 1363323
TI  - Amino acid neurotransmitters in the central control of blood pressure and in
      experimental hypertension.

PMID- 1363325
TI  - The 'serotonin/norepinephrine link' beyond the beta adrenoceptor.
AB  - C6 rat glioma cells were utilized as a model system to probe the
      'serotonin/norepinephrine link' at the level of preproenkephalin (PPE) gene
      expression. The beta adrenoceptor mediated increase in PPE mRNA was attenuated by
      the selective beta 1 adrenoceptor antagonist metoprolol which blocked the
      isoproterenol induced cyclic AMP generation by 97%. The subtype nonspecific
      antagonist propranolol blocked both the isoproterenol induced increase in cyclic
      AMP and the increase in the PPE mRNA steady-state levels. Serotonin (5-HT) had no
      effect on the density of beta adrenoceptors or their down-regulation by
      isoproterenol and did not alter the PPE gene expression in the absence of the
      beta signal. However, 5-HT significantly deamplified the beta signal mediated
      enhancement of the PPE mRNA thus indicating that the aminergic link occurs beyond
      the beta adrenoceptor.

PMID- 1363326
TI  - Muscle-derived differentiation factor increases expression of the tyrosine
      hydroxylase gene and enzyme activity in cultured dopamine neurons from the rat
      midbrain.
AB  - Our earlier work demonstrated that certain populations of brain neurons which do
      not synthesize catecholamine (CA) neurotransmitters in vivo, will, when grown in
      culture with muscle-derived differentiation factor (MDF), unexpectedly express
      the gene for the CA biosynthetic enzyme tyrosine hydroxylase (TH). In this paper,
      we sought to determine whether MDF could also regulate TH expression in those
      neurons which normally synthesize CA neurotransmitters. Incubation of cultured
      dopamine neurons from the ventral midbrain with MDF elevated the levels of TH
      mRNA and TH enzyme activity 5- to 40-fold higher than that measured in control
      cultures. Sympathetic neurons were unaffected by a similar MDF treatment. Unlike
      the 2-day critical period for MDF-responsivity in non-CA neurons. CA neurons
      remained susceptible to MDF's influence over an extended developmental interval
      (E14-18), suggesting that MDF may be important for TH gene regulation in brain CA
      neurons even differentiation is complete. Because of these unique properties, MDF
      may provide a unique opportunity to explore ways in which the TH gene might be
      directly manipulated in these cell populations in order to correct the CA
      imbalances that occur in certain neurological diseases and disorders.

PMID- 1363327
TI  - Hypothalamic neuropeptide expression after food restriction in Zucker rats:
      evidence of persistent neuropeptide Y gene activation.
AB  - The Obese Zucker rat is a model of genetic obesity characterized by hyperphagia,
      hyperinsulinemia and other endocrine abnormalities. In order to elucidate
      pathogenetic mechanisms contributing to disturbed feeding behavior in these
      animals, the effect of food restriction on three hypothalamic neuropeptides
      involved in the control of food intake was studied. Eighteen male obese and 18
      lean Zucker rats were randomly divided into two groups: half of the animals were
      food-restricted for 2 weeks, while the other half served as controls and were fed
      ad libitum. The levels of preproneuropeptide Y (preproNPY), preprocorticotropin
      releasing factor (preproCRF) and preprosomatostatin (preproSOM) mRNAs were
      determined using in situ hybridization technique. In addition, plasma insulin and
      corticosterone concentrations were analyzed. Food restriction significantly
      increased the expression of preproNPY mRNA in the arcuate nucleus in both Zucker
      phenotypes, while the expressions of preproCRF mRNA in the paraventricular
      nucleus (PVN) and preproSOM mRNA in the periventricular nucleus (PeV) were not
      altered. The expression of preproNPY mRNA was significantly greater in control
      obese animals compared to control lean animals. Food restriction lowered plasma
      insulin levels, but did not change plasma corticosterone levels. It is concluded
      that food restriction specifically activates NPY gene transcription in the
      arcuate nucleus the response being similar in both Zucker phenotypes. The results
      suggest that orexigenic NPY plays a role in the adaptation to altered feeding
      status.

PMID- 1363330
TI  - A world united against AIDS. Report on the Nursing Satellite Conference and the
      Eighth International Conference on AIDS, Amsterdam, The Netherlands, 19-24 July,
      1992.
AB  - The dramatic increase of new HIV/AIDS cases in women and their babies continues
      to require midwives to be vigilant in their efforts to identify clients at risk
      for HIV. The role of STDs in HIV transmission and disease progression is evident.
      Research is lacking on the effect of AIDS drugs, pregnancy and birth on the HIV
      infected woman. Prevention, through safer sex, is a critical education strategy
      to consider. Data suggesting intrapartum transmission of HIV is particularly
      interesting and warrants further study. Development of the international
      framework for future clinical vaccine trials is underway. Initial studies on the
      ability of HIV vaccines to limit perinatal transmission may provide some
      encouraging future results.

PMID- 1363329
TI  - Neurotransmitter transporter family cDNAs in a rat midbrain library: 'orphan
      transporters' suggest sizable structural variations.

PMID- 1363328
TI  - Analysis of the human tyrosine hydroxylase promoter-chloramphenicol
      acetyltransferase chimeric gene expression in transgenic mice.
AB  - To investigate cis-elements responsible for catecholaminergic (CAnergic) neuron
      specific expression of the tyrosine hydroxylase (TH) gene, we produced lines of
      transgenic mice carrying 5.0-kb, 2.5-kb and 0.2-kb fragments from the 5'-flanking
      region of the human TH gene fused to a reporter gene, chloramphenicol
      acetyltransferase (CAT), and designated them as TC 50, TC 25, and TC 02,
      respectively, and reporter gene expression in transgenic mice was analyzed by CAT
      assay by immunocytochemistry with anti-CAT antibody. High-level CAT expression
      was observed in the brain and adrenal gland using the 5.0-kb promoter of the TC
      50 mice, but ectopic expression was consistently observed in several somatic
      tissues, e.g. thymus, colon, and testis. In brain, expression was achieved in
      CAnergic neurons with the largest construct (5.0 kb), but not with 2.5 kb or 0.2
      kb of 5' flanking sequence. However, TC 50 mice also expressed CAT
      immunoreactivity in non-CAnergic neurons. In the TC 25 line CAT immunoreactivity
      was detected only in some non-CAnergic neurons. In the TC 02 line no CAT
      immunoreactivity was detected in any of the tissues examined. These results
      indicate that the 5.0-kb DNA fragment of the TH gene upstream region contains
      activity to express CAT in CAnergic neurons and surprisingly, lacks some
      regulatory elements attenuating ectopic expression, and that the 2.5-kb and 0.2
      kb fragment are not sufficient for the proper expression. We discuss the presence
      of the tissue-specific regulatory elements in the structure portion of the TH
      gene and/or 3'-flanking region.

PMID- 1363331
TI  - Leading priorities.

PMID- 1363332
TI  - Modern management of peptic ulcer.

PMID- 1363333
TI  - Molecular Biology of Pigment Cells. Symposium proceedings. Sendai, Japan,
      November 8-9, 1990.

PMID- 1363334
TI  - Molecular genetics and the ontogeny of pigment patterns in mammals.
AB  - The conclusion that animal development is guided by a hierarchical system of gene
      expression and interaction has gained considerable support from recent molecular
      genetic studies on fruit flies (Drosophila melanogaster) and mice (Mus musculus).
      They demonstrate that the patterns of organization revealed by terminal
      differentiation of cells is anticipated by a myriad of transient prepatterns that
      channel the developing embryo toward its genetically-programmed target. The
      numerous white spotting mutants in mice exhibit some of the most dramatic and
      variable patterns of cutaneous melanin pigmentation. Until recently, the
      mechanisms of action of white spotting genes and their relationship to the
      developmental genetic hierarchy remained unknown. It now appears that certain
      white spotting genes may encode growth factors essential for melanoblast
      development. Others may be related to homeobox genes that play a number of
      developmental roles, the primary one being the determination of regional
      organization along the anterior-posterior axis of the early embryo. The patterns
      of homeobox gene expression are consistent with several of the developmental
      models for white spotting in mice and other mammals. It is evident that white
      spotting genes are not solely concerned with the terminal differentiation of
      melanoblasts into melanocytes. They are heterogeneous with regard to action and
      level of expression within the developmental hierarchy.

PMID- 1363336
TI  - [Takayasu's disease associated with liver cirrhosis in a patient with HBs
      antigenemia].

PMID- 1363335
TI  - Neuroleptic treatment is an unlikely cause of elevated dopamine in thalamus of
      schizophrenic subjects.
AB  - Previous studies have indicated a marked increase in the dopamine/norepinephrine
      ratio in thalami of schizophrenic patients compared with those of control
      subjects. Since these results all came from patients who were receiving
      neuroleptic drugs, the possibility exists that the increased dopamine
      concentrations are an effect of medication. To address this question, similar
      analyses were done on thalami from Huntington's Disease patients who had received
      neuroleptic treatment. The results showed no differences between the thalami of
      Huntington's Disease patients and controls, strongly suggesting that chronic
      treatment with neuroleptic drugs does not result in an increase of endogenous
      dopamine in the thalami of human subjects.

PMID- 1363337
TI  - [The effect of long-term treatment with calcium antagonists on the physical work
      capacity of hypertension patients].

PMID- 1363338
TI  - [The use of reaferon in the combined therapy of patients with hemorrhagic fever
      with renal syndrome].

PMID- 1363339
TI  - Comparison of brain tumor growth kinetics by proliferating cell nuclear antigen
      (PCNA) and bromodeoxyuridine (BrdU) labeling.
AB  - The bromodeoxyuridine (BrdU) labeling study provides valuable cell kinetic
      information for individual tumors that could suggest the prognosis of each
      patient who had a tumor. Recently, a monoclonal antibody against the
      proliferating cell nuclear antigen (PCNA or cyclin), a nuclear protein expressed
      in proliferating cells, was developed which could be used on formalin fixed,
      paraffin embedded tissue. The purpose of this study was to compare the cell
      kinetic data obtained by the BrdU labeling study and the PCNA method in the same
      patient. The relationship between labeling indices of BrdU incorporated into S
      phase and PCNA expressed by cycling cells was investigated in 31 patients with
      brain tumors. Both of the labeling indices showed good correlation with
      histological grade of the tumor. The values of the PCNA labeling index (LI) were
      parallel but higher than those of the BrdU LI, and the relation PCNA LI = 2.2 x
      BrdU LI + 0.8 (r2 = 0.86) was obtained. The results of this study show that PCNA
      could replace the BrdU method for identifying the proliferating cells, and the
      major advantages of PCNA method is that it could be done without any pretreatment
      and avoid injection of the teratogenic agent for diagnostic purpose.

PMID- 1363340
TI  - Studies of nonsedative antihistamines. II. Assessment of its antihistaminic
      potency.
AB  - An analysis is made of the effectiveness of terfenadine at dosages of 60 and 120
      mg, of cetirizine at a dose of 10 mg, and of loratadine and ebastine at a dose of
      10 mg in inhibiting the papule induced by 20 mcg of intradermal histamine.
      Although all produced significant inhibition, cetirizine and terfenadine 120 mg
      showed a significantly greater inhibition coefficient than loratadine.

PMID- 1363342
TI  - [The XIII World Congress of Obstetricians and Gynecologists].

PMID- 1363341
TI  - [Changes in the hypophyseal-thyroid system under narcotic action in the
      parturients of a group at high risk of perinatal pathology].
AB  - Eighty-seven parturients were examined to disclose the function of the thyroid
      during narcotic exposure in labor and in cesarean section in cases of high risk
      of giving birth to infants with perinatal abnormalities. Neurotropic agents were
      found to inhibit the fetal hypophyseo-thyroid system in cases with a history of
      intrauterine hypoxia, thus saving this system from exhaustion. Employment of
      various types of general anesthesia in cesarean section in this patient
      population provides an adequate maternal neurovegetative protection from surgical
      aggression.

PMID- 1363344
TI  - Acute ethanol administration and the metabolism of glutamine by skeletal muscle
      of the rat: implications for ethanol-induced reductions in protein synthesis.
AB  - The effect of acute ethanol administration (75 mmol/kg) on the metabolism of
      glutamine by skeletal muscle of the rat was studied in order to investigate the
      hypothesis that the concentration of this amino acid in muscle controls the rate
      of protein synthesis. Ethanol administration was without effect on the
      concentration of glutamine in EDL (extensor digitorum longus) and plantaris
      muscles (Type II fibre-rich muscles), but increased the concentration in soleus
      muscle (Type I fibre-rich muscle). The rate of release of glutamine was increased
      from EDL muscle, but unchanged from soleus muscle of treated animals. Ethanol
      administration was without effect on the maximal activity of glutamine synthetase
      in both soleus and EDL muscles. It is concluded that changes in the concentration
      of glutamine in muscle cannot explain the ethanol-induced changes in the rate of
      protein synthesis. Nevertheless, the increase in the concentration of glutamine
      in soleus muscle following ethanol administration is of interest and may be
      mediated via modulation of the glutamine transporter and/or the activity of
      glutamine synthetase in vivo.

PMID- 1363343
TI  - The carbohydrate epitope 3-fucosyl-N-acetyllactosamine is developmentally
      regulated in the human cerebellum.
AB  - The carbohydrate epitope 3-fucosyl-N-acetyl-lactosamine (CD15) is involved, as a
      constituent of glycoconjugates, in cell-cell interactions and cell sorting during
      rodent CNS morphogenesis. The present study was designed to test whether CD15 is
      also involved in the development of the human CNS. Human cerebellar hemispheres
      and vermes from the 24th week of gestation (wg) to the 26th postnatal month (pnm)
      and from adults were investigated for CD15 immunoreactivity, using the monoclonal
      antibody MMA. Our findings establish that the carbohydrate moiety is
      developmentally regulated in neuronal and glial cells during their
      differentiation. First, the parallel fibers of granule cells are CD15+ during the
      epoch of synaptogenesis with Purkinje cell dendrites. Second, a subpopulation of
      neurons from the dentate nucleus is transiently CD15+ from the 32nd wg until the
      15th pnm. Third, at the onset of myelination (around the 35th wg), CD15
      immunoreactivity is discernible in the cytoplasm of young oligodendrocytes.
      Immunoreactivity on protoplasmic astrocytes of the inner granular layer and on
      fibrous astrocytes of the white matter progressively increases during fetal
      development. In addition, the CD15 epitope is persistently present on Bergmann
      glial processes and ependymal cells. Within the three subdivisions of the
      cerebellum, i.e., hemispheres, vermis, and flocculonodular lobe, the CD15
      expression follows a different timing of morphogenesis. For example, diminution
      of immunoreactivity in the parallel fibers occurs first in the phylogenetically
      older flocculonodular lobe and vermis, and later in the phylogenetically younger
      hemispheres. This study shows that in the human cerebellum the distribution of
      CD15 undergoes marked developmental changes. This epitope may also act in cell-to
      cell recognition, and perhaps could play a role in controlling CNS development.

PMID- 1363345
TI  - Changes in markers of alcohol intake in man below 'safe' drinking levels.
AB  - In a group of 343 working men, only 34 of whom regularly drank more than 60 ml of
      ethanol per day, logistic regression was used to determine the combination of
      biomarkers which best discriminated between those who regularly drank less than
      30 ml or 30 ml or more of ethanol daily. The index consisted of apolipoprotein A
      II, uric acid, gamma-glutamyl transpeptidase and mean corpuscular volume. Even
      with the relatively low level of alcohol intake reported in these subjects
      (assessed using a 7-day retrospective alcohol diary), the groups with higher or
      lower intake of alcohol were separated with a sensitivity of 68%, a specificity
      of 74% and a positive predictive value of 71%. Systolic blood pressure, adjusted
      for age and body mass index, was also linearly related to alcohol intake, and
      when included in the biomarker index improved the proportion correctly classified
      from 71% to 75%. Using the biomarkers only, 94% of subjects regularly drinking at
      least 80 ml of ethanol equivalent per day and 100% of the non-drinkers were
      correctly classified.

PMID- 1363346
TI  - HER-2/neu oncogene expression, DNA ploidy and proliferation index in breast
      cancer.
AB  - HER-2/neu gene expression, DNA ploidy and proliferation index were studied in 250
      cases of breast cancer. Expression of HER-2/neu was determined by using an
      antibody to the HER-2/neu receptor. Ki-67 antibody was used to determine the
      proliferation index of the breast cancers, and the Feulgen method was used to
      assess DNA amounts in the tumor cells. Histochemical staining was quantitated by
      image analysis. Of the cancers studied, 72 were positive for overexpression of
      HER-2/neu protein; of these, 62 (86%) possessed near-tetraploid DNA content, and
      47 (65%) had more than one G0G1 stem line (polyploid) of DNA distribution. Cells
      from the cases negative for HER/2-neu overexpression contained DNA amounts that
      ranged from diploid to varying degrees of aneuploid. A significant difference in
      the amounts of cellular proliferation in HER-2/neu overexpressing cancers was
      found between those that expressed the HER-2/neu receptor on their membranes and
      those that exhibited mainly cytoplasmic receptors.

PMID- 1363347
TI  - Measurement of the immunoperoxidase staining of macrophages within liver
      granulomata of mice infected with Mycobacterium tuberculosis.
AB  - A quantitative image analysis technique developed for the measurement of the
      extent of macrophage activation and epithelioid cell differentiation was
      performed on mice infected experimentally with Mycobacterium tuberculosis. The
      granulomatous inflammatory response within the liver reached a peak at day 23 and
      declined by day 33. Animals of strain B10.BR (H-2k) showed an increased granuloma
      fraction as compared to Balb/k (H-2k) mice, thus confirming the influence of non
      H2 genes in the control of granuloma formation in mice. Using a monoclonal
      antibody against CD11b/CD18 (Mac1;CR3), we observed two subpopulations of
      macrophages within the granulomata. The small, darkly staining cells at the
      periphery of granulomata appear to be newly recruited macrophages. Larger, paler
      staining cells toward the center of granulomata represent activated and mature
      epithelioid macrophages. Using a semiautomated image analyzer (Quantimet 970), we
      measured the relative numbers of these macrophage subpopulations. There were more
      activated macrophages (epithelioid cells) associated with the increased granuloma
      fraction in the B10.BR mice than in the Balb/k. However, similar numbers of newly
      recruited peripheral macrophages were found in both Balb/k and B10.BR strains.
      This technique has shown qualitative as well as quantitative differences in the
      granulomatous inflammatory response in this murine model of tuberculosis in
      strains of mice with quite different antibody repertoires to mycobacterial
      antigens.

PMID- 1363348
TI  - Effects and Side-Effects of Dental Restorative Materials. NIH Technology
      Assessment Conference. Bethesda, Maryland, August 26-28, 1991.

PMID- 1363349
TI  - Minimal growth factor requirements of human fetal kidney in serum- and glucose
      free culture.
AB  - The addition of insulin plus transferrin to Leibovitz's L-15 medium was
      previously shown to restore important cellular functions in a serum-free system
      developed in our laboratory for human fetal kidney explants. The objective of the
      present study was to compare the effectiveness of this insulin plus transferrin
      combination with one used in other in vitro systems whereby serum is substituted
      by a mixture of five hormones (insulin, transferrin, hydrocortisone,
      triiodothyronine and prostaglandin E1). In fetal kidney it was found that the
      combination of insulin plus transferrin was as effective as the five-hormone
      mixture on DNA synthesis after 5 days of culture and was even more effective in
      younger fetuses (10-13 weeks) compared with older fetuses (16-19 weeks). However,
      protein synthesis was more sensitive to the five-hormone combination. Selective
      deletion of individual hormones showed that insulin is the essential factor for
      the growth of cultured kidney explants. Differentiation of brush border membranes
      in nephrons, as evaluated by alkaline phosphatase and gamma-glutamyl-transferase
      activities, was not significantly modified by either of the two combinations. The
      present results indicate that insulin plus transferrin represents the optimizing
      condition for our culture model. The response to supplements varies according to
      fetal age and possibly to tissue proliferation states and/or cell type.

PMID- 1363350
TI  - The baculovirus Autographa californica nuclear polyhedrosis virus genome includes
      a papain-like sequence.
AB  - The published DNA sequence that includes the gene for the envelope glycoprotein
      gp67 of the baculovirus Autographa californica nuclear polyhedrosis virus also
      contains a segment that shows 32% amino acid identity to papain, a cysteine
      endopeptidase from the papaya plant (Carica papaya). The viral papain-like
      sequence is apparently affected by a frame-shift mutation, but otherwise appears
      capable of encoding a functional enzyme. Catalytically essential amino acids
      appear to be conserved, as do disulphide bridges. The overall structure of the
      putative protein is similar to that of papain, as judged by hydropathy profile.
      Secondary structure prediction using a consensus of seven methods indicates that
      the putative viral enzyme retains the alpha/beta domain structure of papain,
      including the long helix beginning with cysteine-25. Infecting SF9 cells with the
      virus did not lead to a detected increase in cysteine endopeptidase activity, and
      a cysteine endopeptidase inactivator appeared to have no effect on infectivity.
      Irrespective of whether the sequence encodes a functionally active cysteine
      endopeptidase, this is the first example of a papain-related sequence in a viral
      genome.

PMID- 1363351
TI  - Oncogenes and tumor suppressor genes.

PMID- 1363352
TI  - Volume dedicated to the memory and achievements of Professor William L. McGuire,
      M.D.

PMID- 1363353
TI  - Growth regulation of human neuroblastoma.

PMID- 1363354
TI  - Kaposi sarcoma: a cytokine-responsive neoplasia?

PMID- 1363355
TI  - BCL-2: physiology and role in neoplasia.

PMID- 1363356
TI  - Activated oncogenes and putative tumor suppressor genes involved in human breast
      cancers.
AB  - Cytogeneticists first proposed that the karyotypic abnormalities identified on
      chromosomes 1, 3, 6, 11, 13, 16, 17, and 18 supported a genetic basis for breast
      cancer. Such abnormal banding patterns, however, may represent either loss-of
      function or gain-of-function molecular events. RFLP analyses have since confirmed
      that 20-60% of primary and spontaneous human breast tumors exhibit allelic losses
      on these same chromosomes, although the exact genes involved at these chromosomal
      sites remain largely unknown. Knowledge gained about the Rb-1 and p53 tumor
      suppressor genes at 13q14 and 17p13 in breast and other human tumors supports the
      paradigm that for any chromosomal locus, allelic loss associated with a mutation
      in the remaining tumor allele signifies an involved tumor suppressor gene. Given
      this paradigm, there are nearly a dozen putative breast tumor suppressor genes
      under active investigation, with most investigators now focusing on various
      chromosome 17 loci. Among the known proto-oncogenes found activated in breast
      cancer, amplification of c-erbB-2 at 17q21 is the most widely studied and
      clinically significant gain-of-function event uncovered to date, occurring in
      about 20% of all primary breast tumors. The involvement of this overexpressed
      membrane receptor has engendered interest in related tyrosine kinase receptors,
      such as EGFR, IR, and IGF-I-R, as well as their respective ligands, which may be
      overexpressed in a greater fraction of tumors, contributing to the autocrine and
      paracrine regulation of breast cancer growth and metastasis. New attention is
      being given to the potentially oncogenic function of structurally altered nuclear
      transactivating steroid hormone receptors, such as ER, whose overexpression has
      long been used to determine endocrine therapy and prognosis for individual breast
      cancer patients. While c-myc was one of the first known proto-oncogenes to be
      found amplified and overexpressed in human breast cancers, the actual incidence
      and clinical significance of its activation remain disputed and in need of
      further study. Lastly, we can expect greater clarification about the importance
      of various 11q13 genes found coamplified in nearly 20% of primary breast cancers,
      and pursuit into the intriguing possibility that a cyclin-encoding gene
      represents the overexpressed locus of real interest in this amplicon. Virtually
      all of these important genetic abnormalities identified thus far are associated
      with but not restricted to human breast cancers. The absence of identifiable
      molecular defects relating to the tissue specificity of this malignancy must be
      considered a substantial gap in our basic understanding of breast
      carcinogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1363357
TI  - Malignant transformation by abl and BCR/ABL.

PMID- 1363358
TI  - The biological and clinical roles of increased insulin receptors in human breast
      cancer.

PMID- 1363359
TI  - Transforming growth factor-alpha and its role in neoplastic progression.

PMID- 1363360
TI  - Growth regulation by transforming growth factor-beta.

PMID- 1363361
TI  - Signal transduction by receptor tyrosine kinases.

PMID- 1363362
TI  - Involvement of G proteins, cytoplasmic calcium, phospholipases, phospholipid
      derived second messengers, and protein kinases in signal transduction from
      mitogenic cell surface receptors.
AB  - Some putative mitogenic signal transduction mechanisms involving G proteins,
      calcium, phospholipases, and protein kinases have been discussed. Several
      elements in this signal transduction scheme are not yet well understood and
      require further experimental investigation. With regard to the heptahelix
      receptors, exactly how do they activate PLA2? Is PLA2 activation linked to
      mitogenic pathways? Is this via stimulation of protein kinase C or perhaps
      another mechanism? How do heptahelix receptors activate tyrosine phosphorylation,
      and is it important in their ability to stimulate cell growth? With regard to the
      various phospholipases that are thought to be regulated by receptor-mediated
      stimuli, only PI-PLC beta and PI-PLC gamma are well characterized. PLA2, PC-PLD,
      and PC-PLC require further study in regard to determination of molecular
      structure and elucidation of mechanisms of phospholipase activation (e.g., what
      are the molecular mechanisms whereby tyrosine kinases and Ras affect PC-PLC?).
      The protein kinase C dependent and protein kinase C independent mechanisms that
      enable mitogenic stimuli to activate the Erk/MAP kinase are enigmatic at this
      time. How Raf-1 activates SRE-containing gene promoters (such as the fos
      promoter) is also not known. However, given the current rapid rate of progress in
      this field, it is likely that a much more complete understanding of the mitogenic
      signal transduction process will soon be obtained.

PMID- 1363363
TI  - Fos and Jun: inducible transcription factors regulating growth of normal and
      transformed cells.

PMID- 1363365
TI  - Normal and malignant growth control by p53.

PMID- 1363364
TI  - DNA binding by the Myc oncoproteins.
AB  - The c-Myc protein is a potential activator of transcription, with the ability to
      bind in a heterodimer form with Max to DNA sequences containing the core
      hexanucleotide sequence CAC(G/A)TG. These properties are shared with L-Myc, a
      homologous oncoprotein expressed in small cell lung carcinoma cells; with N-Myc,
      expressed in neuroblastoma cells; and with avian v-Myc, the c-Myc homolog
      expressed by a chicken retrovirus. The c-Myc, and probably v-Myc, proteins also
      have nonspecific DNA binding function, which may improve the kinetics of specific
      DNA binding. Curiously, this domain appears not to be conserved in L-Myc or N-Myc
      [22]. The data that have accumulated to date are consistent with a model in which
      a c-Myc/Max heterodimer positively regulates the transcription of growth-related
      genes, with Max homodimer functioning as a negative regulator of the same genes
      (Fig. 4) [55]. Max is expressed constitutively at low levels, whereas c-Myc is
      expressed at low levels in quiescent cells, but high levels of c-Myc are induced
      by mitogenic stimulation [56]. Thus, in proliferating cells c-Myc/Max
      heterodimers might bind to the regulatory elements of growth-related genes, where
      the c-Myc TAD might stimulate transcription. Conversely, in quiescent cells with
      little c-Myc present, Max homodimers might predominate. They might bind to
      exactly the same regulatory elements, but due to the apparent absence of a TAD in
      Max [36], transcription might be repressed. Validation of this model will require
      the demonstration of clear regulation of a physiological promoter of a growth
      related gene by c-Myc/Max. Although it is widely believed that Myc proteins
      function as transcriptional activators, this hypothesis has only been
      conclusively supported recently [57, 58]. A theory that c-Myc plays a role in DNA
      replication is not as well substantiated at this point. It is even possible that
      Myc might be involved in both transcription and replication. Although the
      function of these fascinating proteins has been enigmatic for a decade, the rate
      of progress in our understanding of Myc function is accelerating. Such progress
      will undoubtedly lead to a deeper appreciation of this protein, which lies at the
      crossroads of cellular proliferation and oncogenesis.

PMID- 1363366
TI  - Nucleoside diphosphate kinases, nm23, and tumor metastasis: possible biochemical
      mechanisms.

PMID- 1363367
TI  - Oncogenes in human lung cancer.
AB  - The rapid pace of research in the genetics of human cancer will predictably
      render any review of the topic out of date by the time of its publication.
      Prospects for the near future will likely include the identification of a
      chromosome 3p gene(s) linked with the development of familial renal cancer and,
      perhaps, also lung cancer. In addition, the availability from the Human Genome
      Project of an increasing number of well-characterized markers will accelerate the
      search for additional human recessive oncogenes. Many questions still remain
      about the etiology of lung cancer and how to apply this information for patient
      care. For example, identification of the cell of origin for small cell and non
      small cell lung cancers will facilitate our understanding of the development of
      these tumors and improve the possibilities for future preventive strategies. In
      addition, we now realize that these cancers arise from the sequential
      accumulation of multiple genetic mutations (Table 3; Fig. 1). Therefore, a
      central question is which of these targets are essential for the process of
      carcinogenesis, and whether there is a critical temporal order for this process
      with a defined premalignant phase in a discrete field of bronchial tissue. In
      addition, are there genetically inherited susceptibilities to the development of
      lung cancer (either directly or via variabilities in carcinogen metabolism) that
      could be accurately identified in the general population? Finally, is there a
      rate-limiting mutation and will the genetic correction of this defect suffice to
      restore growth regulation, or will the replacement of multiple gene products be
      required for tumor suppression? We are already witnessing the beginnings of the
      use of molecular diagnostic markers as a research tool for assigning prognostic
      information. The expression of neuroendocrine markers in non-small cell lung
      cancer has recently been applied as an indicator of the potential response to
      combination chemotherapy [15]. Similar methods are being applied to the
      expression of tumor suppressor genes or the presence of somatic mutations in
      dominant oncogenes such as the ras gene. However, the clinical benefit of this
      prognostic information with currently available treatment programs is still
      uncertain.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1363368
TI  - Thyroid growth factors and oncogenes.

PMID- 1363369
TI  - [Clinical and anatomopathologic study of 800 cryptorchid testis].
AB  - 662 children (800 cryptorchid testes) has been studied in order to check if the
      age and location were important factors in the degree of the lesion found in the
      biopsy. We have related in this survey the tubular fertility index (IFT) and
      tubular diameter (DT) to the age and location of the testes and we have not
      proved statistically their relationship, for which reason we do not advise to
      plan the age of surgery in terms of possible anatomopathologic damage.

PMID- 1363371
TI  - Pancreaticogastrostomy after pancreatoduodenectomy.
AB  - The aim of this study was to evaluate the place of pancreaticogastrostomy (PG) in
      reducing pancreatic fistula after pancreatoduodenectomy. From January 1988 to
      June 1991, 32 consecutive patients (mean age, 57 years) were operated on, 25 for
      malignant disease (78%). The pancreatic remnant was normal in 17 patients (53%)
      and sclerotic in the others. There was one operative death (3.1%) unrelated to
      PG. Post-operative complications occurred in five patients (16%). Only two
      complications were related to PG: 1 patient had anastomotic intra-gastric
      bleeding and was reoperated on, 1 patient with a normal pancreatic remnant
      developed a pancreatic fistula (3.1%) treated conservatively. Reported series of
      PG, as well as our results, demonstrates that PG is associated with a dramatic
      decrease of both pancreatic fistula and mortality rates. The risk of anastomotic
      haemorrhage can be reduced by preventative ligation of submucosal gastric
      vessels. In conclusion, PG appears as a simple and reliable method of management
      of the pancreatic remnant after pancreatoduodenectomy.

PMID- 1363370
TI  - Regional expression of the Wnt-3 gene in the developing mouse forebrain in
      relationship to diencephalic neuromeres.
AB  - During early vertebrate development, a series of neuromeres divides the central
      nervous system from the forebrain to the spinal cord. Here we examine in more
      detail the expression of Wnt-3, a member of the Wnt gene family of secreted
      proteins, in the developing diencephalon, in comparison to the expression of the
      homeobox gene Dlx-1. In 9.5-day mouse embryos, Wnt-3 is expressed in a restricted
      area of the diencephalon before any morphological signs of subdivisions appear.
      Around embryonic day 11.5, Wnt-3 expression becomes restricted to one of the
      neuromeres of the diencephalon, the dorsal thalamus. Dlx-1 is expressed in a non
      overlapping area immediately anterior to and abutting the Wnt-3 expressing
      domain, corresponding to the ventral thalamus. In addition, Wnt-3 is expressed in
      the midbrain-hindbrain region. In the adult mouse, Wnt-3 and Dlx-1 are expressed
      in subsets of neural cells derived from the original areas of expression in the
      diencephalon. Taken together, our results suggest that Wnt-3 and Dlx-1 provide
      positional information for the regional specification of neuromeres in the
      forebrain. The continued expression of these genes in the adult mouse brain
      suggests a distinct role in the mature CNS.

PMID- 1363372
TI  - [Detection of the HIV p24 antigen on lymphocyte membranes using flow cytometry].
AB  - The evaluation of the presence of p24 antigen on the membrane of peripheral blood
      mononuclear cells from 31 HIV infected individuals is presented. The study was
      performed by indirect immunofluorescence and flow cytometry and the data were
      analyzed by the Kolmogorov-Smirnov test. Values obtained [D/s(n)] result from the
      comparison of the fluorescence histograms of each sample with a control one.
      Cases showing p24 Ag on peripheral blood mononuclear cells also presented
      percentages of CD3, HLA-DR positive cells significantly higher than p24 negative
      ones. In addition, D/s(n) values were superior in symptomatic patients than in
      asymptomatic ones, which indicate the existence of a correlation between flow
      cytometry results, viral replication and clinical course. Nevertheless in this
      study, as well and in previous ones, a high degree of cross reactivity between
      the anti-p24 monoclonal antibody employed and normal lymphocytes has been
      observed. This reactivity is localized preferentially in the CD4 positive subset.

PMID- 1363374
TI  - Fourth International Congress on Tumour Necrosis Factor and Related Cytokines.
      Meeting at Koningshof, Veldhoven, The Netherlands 2-6 May 1992.

PMID- 1363375
TI  - Effects of beta-blocking drugs in alcohol withdrawal: a double-blind comparative
      study with propranolol and diazepam.
AB  - Alcohol withdrawal is associated with a decrease in gamma-aminobutyric acid
      neurotransmission. This explains the efficacy of benzodiazepines. However, an
      increase in adrenergic activity may also play a part in alcohol withdrawal
      symptoms, suggesting a potential efficacy of beta-blocking drugs. A double-blind
      comparative study of propranolol and diazepam was carried out in 28 patients
      suffering from moderate uncomplicated alcohol withdrawal. Patients were treated
      for 15 days with either 75 mg of propranolol or 30 mg of diazepam. The results
      show that both drugs at the dosages used are equipotent in reducing physical
      withdrawal symptoms and anxiety symptoms. This suggests that most likely the
      central as well as the peripheral effects determine the clinical usefulness of
      propranolol in the management of alcohol withdrawal. However, propranolol is
      ineffective in preventing major motor seizures, suggesting that different
      neurobiological mechanisms underlie the alcohol withdrawal symptoms.

PMID- 1363377
TI  - [Hormone and breast cancer, from biology to the clinic. International symposium
      of the 9th International Congress of Endocrinology. Nice, France, 29-30 August
      1992. Abstracts].

PMID- 1363373
TI  - Effects of 2-deoxy-D-glucose on the glucose metabolism in Saccharomyces
      cerevisiae studied by multinuclear-NMR spectroscopy and biochemical methods.
AB  - The effects of various concentrations of deoxyglucose (DG) on the aerobic
      metabolism of glucose in glucose-grown repressed Saccharomyces cerevisiae cells
      were studied at 30 degrees C in a standard pyrophosphate medium containing 4.5
      10(7) cells/ml. 31P-nuclear magnetic resonance (NMR) spectroscopy was used to
      monitor DG phosphorylation and the formation of polyphosphates. The production of
      soluble metabolites of glucose was evaluated by 13C- and 1H-NMR and biochemical
      techniques. The cells were aerobically incubated with 25 mM of glucose and
      various concentrations of DG (0, 5 and 10 mM) in order to determine the DG
      concentration leading to optimum of 2-deoxy-D-glucose 6-phosphate (DG6P)
      formation without over-inhibiting the synthesis of other metabolites. The
      production of DG6P increased by about 25% when the external DG concentration was
      doubled (from 5 to 10 mM). The formation of polyphosphates (polyP), on the other
      hand, was found to be mainly conditioned by the DG concentration. The amount of
      polyP decreased by a factor of four upon addition of 5 mM DG and became
      undetectable in the presence of 10 mM DG. The glucose consumption and the
      production of soluble metabolites of [1-13C]glucose were then evaluated as a
      function of time in both the absence and presence of 5 mM DG. The effect of DG is
      to decrease the glucose consumption and the formation of polyphosphates, ethanol,
      glycerol, trehalose, glutamate, aspartate and succinate while stimulating the
      formation of arginine and citrate. Upon co-addition of 25 mM glucose and 5 mM DG,
      the ratio between the initial rates of glucose consumption (0.16 mM/min) and DG6P
      production (0.027 mM/min) is about (5.9 +/- 1.2), not very different from the
      ratio of the initial concentration of glucose and DG (= 5.0). Therefore,
      hexokinase can phosphorylate deoxyglucose as well as glucose. However, after 100
      min of incubation, the glucose concentration in the external medium decreased by
      about 64% while only 10% of DG was phosphorylated. DG6P was formed and quickly
      reached the limiting value about 30 min after co-addition of glucose and DG.
      Nevertheless, when the maximum quantity of DG6P was obtained, the DG consumption
      became negligible. By contrast, the glucose consumption and the production of
      ethanol and glycerol, although substantially reduced by about 42%, varied
      linearly with time up to 80 min of incubation. Thus even in the presence of an
      excess of DG, glycolysis is only slowed but not gradually or completely inhibited
      by DG.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1363378
TI  - GEM 91--an antisense oligonucleotide phosphorothioate as a therapeutic agent for
      AIDS.

PMID- 1363376
TI  - [The immunotropism of sunflower oil and starch in peroral administration to
      mice].
AB  - It has been shown that per os introduction of sunflower oil and starch to adult
      thymectomized mice resulted in reconstitution of the number of Thy-I+ spleen
      cells similar of the glutamic acid effect. Glutamic acid restored the immune
      response to sheep red blood cells (SRBC), however, sunflower oil and starch were
      not effective. The influence of these compounds on the immune response to SRBC in
      normal and sham-thymectomized mice was different: glutamic acid stimulated it,
      starch had no influence on the immune response, sunflower oil suppressed it.

PMID- 1363379
TI  - Intracellular glutathione and its metabolizing enzyme activities in a metastatic
      variant melanoma cell line.
AB  - Levels of glutathione peroxidase (GSH-PX), glutathione-S-transferase (GST), gamma
      glutamyl transpeptidase (gamma GTP) and glutathione reductase (GR) activities in
      the B16-F10 metastatic melanoma cell line are higher than those in non-metastatic
      B-16 murine melanoma cells. An inverse relationship was observed between the
      level of reduced glutathione (GSH) and metastatic capacity. Interferon (IFN), an
      antitumour and antimetastic agent, reduced the experimental metastatic capacity
      of B16-F10 cells while increasing the intracellular GSH content. This was
      associated with a fall in activity of GSH-metabolizing enzymes. These results
      suggest a correlation of intracellular GSH and its metabolizing enzymes with
      malignant transformation.

PMID- 1363381
TI  - DNA fingerprinting in the Chinese with an oligonucleotide probe (GTG)5.
AB  - DNA fingerprinting is a very powerful tool that enables specific identification
      of individuals. In order to study fingerprinting patterns in the Chinese, the
      oligonucleotide probe designed by Epplen et al was used. Peripheral blood
      leukocyte DNA was digested with restriction enzyme Hinf I and probed by (GTG)5.
      Normal females and males were tested; all revealed very different DNA
      fingerprints. Most of the discernible bands in the gel were polymorphic; there
      was no specific association between any polymorphic band and the sex of the
      individual tested. In situ gel-hybridization was used with the oligonucleotide
      probe, and after electrophoresis, all procedures could be completed within one
      working day. Three patients who had received bone marrow transplants from their
      respective siblings had the same fingerprints as their donors. The inheritance of
      all bands from either the father or mother proved parents' authenticity. DNA
      fingerprinting with a oligonucleotide probe is obviously a useful technique.
      Clinical application may include engraftment monitoring, zygosity determination
      and paternity testing.

PMID- 1363380
TI  - Biological and enzymatic features of human melanoma clones with different
      invasive potential.
AB  - Cell clones derived from a human melanoma metastasis selected for different
      integrin profiles were examined in vitro for invasive potential and biological
      and biochemical features potentially related to this process. Clones which
      expressed high levels of integrins showed high invasive potential, extracellular
      matrix degradation, and adhesion to gelatin-coated substrates. A correlation was
      also found between invasiveness and intracellular and extracellular plasminogen
      activator activity. Heparanase and collagenase type IV activities were apparently
      unrelated to invasiveness. gamma-Glutamyl transferase (GGT) activity was high in
      highly invasive clones, whereas melanin content was high in slightly invasive
      clones. Heterogeneity was also observed in cellular parameters such as cell
      dimensions, growth features and DNA index. The intrinsic biological and
      biochemical heterogeneity of a cell population derived from a single metastasis
      may be responsible for the different behaviour of clones, regardless of their
      invasive potential. Since slightly invasive cells are more differentiated than
      highly invasive cells, malignancy and differentiation are inversely correlated in
      such human melanoma clones.

PMID- 1363382
TI  - Serum interleukin-2 and soluble interleukin-2 receptor in renal transplant
      recipients.
AB  - Interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R), released during
      T-lymphocyte activation, were measured in serial samples of serum from 32
      patients with renal allografts and other uremic patients. Patients undergoing
      chronic hemodialysis had elevated sIL-2R levels (1,801.93 +/- 753.23 U/mL) which
      dropped after stable renal transplantation (822 +/- 438 u/mL). However, these
      values were higher than those of a normal control group (397.3 +/- 84.5 u/mL, p <
      0.01). Marked elevation of sIL-2R (1,503.78 +/- 640 u/mL) was noted in patients
      with acute rejection episodes compared to those in a stable allograft condition
      (p < 0.02) and those with cyclosporine nephrotoxicity (793.2 +/- 245.2 u/mL, p <
      0.01), but returned to a stable level after successful anti-rejection treatment
      (745.91 +/- 345.8 u/mL, p < 0.01). Acute tubular necrosis and infection also
      showed a comparable rise in the sIL-2R level. The increase in sIL-2R with
      rejection was found one to four days earlier than the clinical diagnosis of acute
      rejection. There was a marked rise in the serum IL-2 level of uremic and post
      transplant patients when compared to normal subjects (34.76 +/- 32.16 u/mL and
      9.3 +/- 12.7 u/mL vs 4.38 +/- 3.38 u/mL, p < 0.001), but no significant
      differences were found between the IL-2 level of patients with acute rejection
      and cyclosporine nephrotoxicity or acute tubular necrosis (3.74 +/- 4.51 u/mL,
      1.57 +/- 1.25 u/mL and 6.73 +/- 6.3 u/mL, p > 0.05). The diagnostic value of sIL
      2R assay was more meaningful than that of IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363383
TI  - Microencapsulated pancreatic islets: a pathologic study.
AB  - Dog pancreatic islets isolated by an enzymatic digestion method were encapsulated
      in an alginate-poly L-lysine-alginate membrane. These microencapsulated
      pancreatic islets were cultured in vitro to study their ability of insulin
      secretion. Portions of these in vitro-cultured microencapsulated pancreatic
      islets were taken out for a viability dye exclusion study as well as for
      pathologic studies to correlate them with insulin secretion ability. We found
      that there was a strong correlation between them. Good insulin-secreting
      microcapsules showed well-preserved cell membranes and beta-cell granules. An in
      vitro culture for one to two days in RPMI-1640 made the islets more stable, the
      cellular surface became smoother and the beta-granules were in better shape. The
      microencapsulated pancreatic islets were also injected into the peritoneum of
      streptozotocin-induced diabetic CDF1 mice. Blood glucose levels dropped and
      stayed low for up to 60 days. But, when non-encapsulated dog pancreatic islets
      were used, the blood glucose levels remained low for only about 14 days. A small
      portion of the injected microcapsules were washed out at specific times for
      pathologic study. Up to 28 days after injection, only a few of the injected
      microcapsules showed pericapsular cellular infiltrate. However, after 56 days,
      most of the microcapsules showed dense pericapsular cellular infiltrate.
      Immunohistochemical analysis of these infiltrates showed that the majority of
      cells were fibroblasts and macrophages. Most of the cells located in the inner
      portion of the infiltrate were fibroblasts, while the macrophages were located
      mainly on the outer portion. Both scanning and transmission electron microscopy
      showed that the surface of the microcapsule outer wall was much smoother than the
      inner wall. The size of the microcapsules was approximately 0.6-0.8 mm and the
      thickness of the wall measured around 10 nm. The smaller the microcapsule is, the
      less chance there is of rupture with release of the xenographic islets. Once the
      wall of the transplanted microcapsules was ruptured, the inner surface showed
      more increased inflammatory cell and fibroblast infiltration than the outer
      surface.

PMID- 1363384
TI  - Reproducibility of the measurement of insulin sensitivity by the modified insulin
      suppression test.
AB  - A significant increase in insulin resistance has been implicated in many human
      diseases and the absence of a simple, accurate, reproducible measurement of in
      vivo insulin sensitivity has become a major concern. In order to evaluate the
      reproducibility of insulin sensitivity measured by the modified insulin
      suppression test, 12 healthy young Chinese men were subjected to the same test
      two weeks apart. After three days on a standard diet and an overnight fast,
      somatostatin (350 micrograms/h), insulin (25 mU/m2/min) and glucose (240
      mg/m2/min) were infused concomitantly for three hours. A steady state plasma
      glucose (SSPG) concentration achieved during the last 30 minutes of infusion
      represented the measurement of insulin sensitivity. Comparisons between the
      metabolic clearance rate of insulin (MCRi), plasma total triglyceride and
      lipoprotein cholesterol fractions on two different days were carried out. The
      results indicated that mean SSPG concentrations on Day 1 (5.73 +/- 0.43 mmol/L)
      correlated with mean SSPG concentrations on Day 14 (5.51 +/- 0.38 mmol/L; r =
      0.82, p < 0.002). The relationship slope did not differ from 1 (0.74, p > 0.05),
      the intercept was close to the origin (1.24 mmol/L, p > 0.05) and the mean
      coefficient of intra-individual variation was 10.3%. There was no difference
      between the MCRi for Day 1 and Day 14 (529 +/- 26 vs 526 +/- 24 mL/m2/min, p =
      NS), with a mean coefficient of intra-individual variation of 6.9%.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1363385
TI  - Congenital hypothyroidism in Taiwan: experience before mass screening.
AB  - The clinical data of 91 patients with congenital hypothyroidism, not detected by
      neonatal screening, were reviewed. Our results disclosed that congenital
      hypothyroidism in Taiwan is more common in girls than boys, with a female to male
      ratio of 1.8:1. The majority of our patients were from a first pregnancy. Only
      4.8% of our patients had a history of prolonged gestation, and the median value
      of birth weight in these patients was 3,300 g. Both of these data are comparable
      to those of the normal population. Short stature, constipation, dry skin and
      periorbital edema were the most common symptoms and signs. An ectopic thyroid
      gland was the most common type of congenital hypothyroidism in our series. The
      conditions of most of our patients were detected after the age of three months;
      poor mental prognosis was expected. However, it is hoped that neonatal screening
      programs for congenital hypothyroidism in Taiwan can improve such situations.

PMID- 1363386
TI  - Morbidity and mortality trends of pulmonary tuberculosis in Taiwan.
AB  - An epidemiologic study of pulmonary tuberculosis was carried out to examine the
      secular trend and geographic variations of the incidence, prevalence and
      mortality of pulmonary tuberculosis in Taiwan. The prevalence and incidence rates
      declined-steadily from 1910 to 1980, but have remained unchanged during the last
      decade. Mortality also showed an 8.0% annual decrease from 1974 to 1986, but has
      remained constant without any apparent changes in recent years. Mortality for
      pulmonary tuberculosis is much higher in the aboriginal areas, where patients
      have a poor adherence to treatment and where a high prevalence of alcohol abuse
      exists. The mortality for pulmonary tuberculosis in Taiwan is higher than that in
      most developed countries, such as the U.K. and the U.S.A., but is lower than that
      in mainland China and the Republic of Korea.

PMID- 1363387
TI  - Predictive value of total body bone mineral density for vertebral fractures in
      elderly women. Geriatric Study Group.
AB  - In a general population-based geriatric disease survey in Taipei City, the bone
      mineral density (BMD) of 58 women over 65 years of age was measured for the whole
      body, lumbar spine (L2-L4), and proximal femurs using a 153Gd based dual photon
      absorptiometer. These women were found to have at least one vertebral fracture.
      The results showed that the BMD readings of both the lumbar spine (L2-L4) (mean Z
      score +/- SEM = 0.05 +/- 0.12) and the femoral neck (mean Z score +/- SEM = -0.20
      +/- 0.10) were not statistically different from those of age-matched controls.
      However, the total body BMD in these 58 patients was significantly lower than in
      the normal controls (mean Z score +/- SEM = -1.07 +/- 0.10, p < 0.0001). In the
      normal control group (N = 69, age 50-85), there was a significant linear
      correlation between the total body and lumbar BMD (r = 0.81, p < 0.0001). This
      correlation was not found in the 58 women with vertebral fractures (r = 0.14,
      NS). Our results suggest that geriatric women with vertebral fractures are more
      osteoporotic than normal aged women, even though they have a relatively mild
      degree of spinal osteoporosis. But, because of age-associated degenerative
      changes or other factors, conventional anteroposterior lumbar BMD measurements
      cannot detect the difference. The total body BMD readings, but not the lumbar or
      femoral neck BMD readings, seem to be less affected by these local changes and
      may provide a better discriminative or predictive value for vertebral fracture in
      this particular age group.

PMID- 1363389
TI  - Experimental structural scoliosis in rabbits.
AB  - Structural scoliosis was produced by purely posterolateral mechanical tethering
      of the spine with ligation of the scapula to the opposite pelvic bone in rabbits
      during the growing period. It is a simple and easy method without direct trauma
      to the spine. When the tethering force occurred discontinuously or only in the
      coronal plane by drawing of the scapula to the ipsilateral pelvic bone in 17
      rabbits, spinal deformity could not be produced. The model provided evidence of
      biplanar deformity as one of the initial factors for the development of
      structural scoliosis.

PMID- 1363388
TI  - Management of infected tibial intramedullary nailing using an organized treatment
      protocol.
AB  - Twenty cases of osteomyelitis, following intramedullary nailing of tibial shaft
      fractures, were managed with a prospective treatment protocol, comprising
      intramedullary reaming debridement, antibiotic-bead depot, external skeletal
      fixation, microvascular muscle flap and early cancellous bone grafting. The
      follow-up period ranged from 25 to 48 months (average, 34.3 months). Pseudomonas
      aeruginosa (37.5%) and Staphylococcus aureus (20.8%) were the organisms most
      commonly involved. There were eight united and 12 ununited fractures after
      reaming debridement surgery. Nineteen infections were initially arrested by one
      debridement. One infection was arrested by two Sequential debridements. All 12
      ununited fractures were stabilized by Hoffmann unilateral external fixation until
      the fracture healed. The time spent in external fixation ranged from three to
      seven months (average, 5.2 months). Early cancellous bone grafting was
      successfully accomplished for nine ununited fractures with major debridement bone
      loss. The average union time of the nine fractures with bone grafting was 6.5
      months (range, from six to eight months). We believe that this treatment protocol
      gives a predictable and rapid recovery. The complications were infection
      recurrence in two cases at the old tibial shaft fracture sites, minor Hoffmann
      pin tract infection in two cases and stiffness in two ankles and one knee.

PMID- 1363391
TI  - Intracavernous self-injection therapy for the treatment of erectile dysfunction.
AB  - Fifty-one patients with chronic erectile dysfunction were selected for this study
      involving intracavernous self-injection therapy with papaverine or prostaglandin
      E1 (PGE1). Patients were screened and grouped as follows: pronounced
      vasculogenic, mild vasculogenic, venous leakage, neurogenic and psychogenic
      impotence. The duration of follow-up in these 51 patients was from 1.5-30.5
      months (average, 11.8 months). The average effective dosage of papaverine and
      PGE1 was variable among the different groups. This kind of therapy proved to be
      effective in our preliminary results, which showed that 35 patients (68.6%) were
      found to be good responders and eight patients (15.7%) were temporary responders.
      In our detailed questionnaire, answered by all 51 patients, we found 29 patients
      (56.9%) had increased their frequency of sexual activity, 38 patients (74.5%) had
      sustained their erection more than they ever had before, and 43 patients (84.3%)
      had enjoyed sexual orgasm following this pharmacologically assisted erection.
      Compared with papaverine, PGE1 was found to have fewer complications. None of the
      patients complained of any discomfort after long-term, self-injection with PGE1.
      However, two patients (3.9%) had sustained erections and two patients (3.9%)
      developed palpable fibrotic plaque after papaverine injection in our study.

PMID- 1363390
TI  - Dissociation of inhibitory effects of low-dose ASA on thromboxane production and
      platelet aggregation in ischemic stroke patients.
AB  - Acetylsalicylic acid (ASA) inhibits thromboxane production and hence platelet
      aggregation. However, individual variations in platelet aggregability and serum
      thromboxane B2 (TxB2) concentration after a low dose of ASA (40 mg/day) have been
      reported. To clarify this issue, we studied plasma thromboxane levels and
      platelet aggregation in 43 ischemic stroke patients. Of the 22 patients who
      received 100 mg of ASA daily, dissociation between inhibitory effects of ASA on
      the plasma TxB2 level and threshold concentrations of adenosine diphosphate was
      found in three cases after one month of drug administration, and in three cases
      after six, 12 and 18 months of ASA therapy. This dissociation also developed in
      two patients after one month and six months, respectively, of treatment in the 21
      patients who received 300 mg of ASA daily. The dissociation between the
      inhibitory effects on plasma TxB2 and the circulating platelet aggregate ratio
      was found in two cases after taking medication for one month, and in four cases
      after six, 12, 18 and 24 months of therapy in the 100 mg ASA group. In the 300 mg
      ASA group, dissociation was noted in two cases after one month of medication, and
      in two cases after six and 12 months of medication. In these patients, although
      their TxB2 levels were inhibited to almost unmeasurable levels, platelet
      aggregation was still not inhibited. This ASA inhibitory dissociation phenomenon
      on platelet function may be due to the low dose of ASA, individual differences in
      platelet function in response to ASA therapy, or factors other than those
      involved in the cyclooxygenase system.

PMID- 1363392
TI  - Extracorporeal shock-wave lithotripsy of gallbladder stones.
AB  - Recently, extracorporeal shock-wave lithotripsy has been introduced as a
      nonoperative treatment for gallstone disease. To evaluate its applicability in
      Taiwan, where cholesterol stones are not very frequent, 18 patients out of 194
      (9.3%) were selected according to the Munich inclusion criteria to receive this
      treatment. Chenodeoxycholic acid and ursodeoxycholic acid were administered as
      adjunctive litholytic therapy. Twenty-eight sessions of lithotripsy were
      performed, resulting in a 83% satisfactory fragmentation rate (< or = 5 mm). No
      serious complications were encountered; however, two patients later underwent
      laparoscopic cholecystectomy. The stones disappeared in four patients after
      treatment, but recurred in one after discontinuation of oral bile acids. The long
      term result was discouraging compared to European reports. A 13% stone-free rate
      was noticed at one year and 25% was anticipated during the 13-18 month follow-up.
      It is our conclusion that low eligibility, low cost-effectiveness and poor
      treatment results will restrict the wide-spread use of this nonoperative therapy
      in Taiwan.

PMID- 1363393
TI  - Malignant rhabdoid tumor arising from soft parts of the right thigh with unusual
      neurologic manifestation: report of a case.
AB  - A case of malignant rhabdoid tumor (MRT) arising from the soft tissue of the
      right thigh in a 49-year-old Chinese female with peripheral neuropathy is
      reported. The tumor, exhibiting the salient features of MRT, was composed of
      sheets and nests of polygonal cells with prominent nucleoli and characteristic
      paranuclear inclusion-like hyaline globules under light microscopy which
      corresponded to aggregates of intermediate filaments under electron microscopy.
      The results of immunohistochemical studies of the tumor cells were also
      characteristic: cytokeratin (+), vimentin (+), epithelial membrane antigen (EMA)
      (+), desmin (-), myoglobin (-), leukocyte common antigen (LCA) (-), kappa (-),
      lambda (-), IgG (-) and IgA (-). Serologic study revealed an M-component of IgA.
      The clinical evolution of the patient was highly aggressive and inevitably
      lethal. An adult malignant rhabdoid tumor is unusual, and its association with
      peripheral neuropathy and the coexistence of an M-component of IgA in this case
      appears to be unique. In this report, the differential diagnosis of
      histopathologic features, the association of peripheral neuropathy and the
      coexistence of an M-component of IgA are discussed.

PMID- 1363394
TI  - Diffuse panbronchiolitis: report of a case.
AB  - A 33-year-old male presented with a productive cough of yellowish sputum which he
      had had for several years and progressive dyspnea on exertion that had been
      present for one year. Physical examination on admission disclosed clubbing of the
      fingers, diffuse inspiratory crackles and some rhonchi on auscultation. Plain
      chest film showed diffuse fine nodular lesions in both lungs. Pulmonary function
      tests demonstrated obstructive ventilatory impairment with a positive
      bronchodilator response. A CT scan of the chest showed diffuse fine nodular
      infiltrations in both lung fields. Arterial blood gas analysis of the patient,
      while breathing room air, revealed mild hypoxemia. The histologic findings of an
      open lung biopsy specimen were compatible with a diagnosis of diffuse
      panbronchiolitis. The patient was treated with erythromycin and a bronchodilator,
      and was regularly followed at the outpatient department. In this report, clinical
      manifestations, diagnostic criteria and recent advances in the treatment of
      diffuse panbronchiolitis are discussed.

PMID- 1363395
TI  - Hyperoxaluria, nephrolithiasis, nephrocalcinosis and renal failure after massive
      resection of the small intestine: report of a case.
AB  - Hyperoxaluria is frequently seen in patients with inflammatory bowel disease, or
      after resection of the ileum. It is assumed to be responsible for the development
      of nephrolithiasis, nephrocalcinosis (oxalate nephrosis) and progressive renal
      impairment in these patients. Steatorrhea may aggravate the severity of
      hyperoxaluria. A 60-year-old male underwent massive resection of the jejunum and
      ileum 10 years prior to admission, due to strangulation of the small bowel, with
      occlusion of the superior mesenteric artery. He remained well except for
      steatorrhea which developed two-and-a-half years prior to admission, when
      microhematuria, proteinuria and oxaluria developed progressively. Since that
      time, the nephrolithiasis, nephrocalcinosis and renal failure have continued to
      worsen despite therapy with oxalate restriction and oxalate-binding agents. A
      renal biopsy, performed late in the clinical course, showed severe changes in the
      renal parenchyma. The decline in renal function proved irreversible. The unusual
      metabolic consequences of massive resection of the small intestine and their
      mechanisms are discussed.

PMID- 1363396
TI  - Choriocarcinoma presenting as a unilateral renal mass and gross hematuria in a
      male: report of a case.
AB  - Choriocarcinoma of the kidney, either primary or metastatic, is rarely reported
      in the literature. We encountered a male patient with choriocarcinoma of the
      right kidney. The patient initially presented with fever, gross hematuria and
      flank pain. He had initially been unsuccessfully treated for bilateral renal
      stones for four months before an accurate diagnosis was made. The disease was
      verified only after a resection of the right kidney and meticulous examination of
      microscopic sections of the tumor. Further immunohistochemical study strongly
      supported the diagnosis of choriocarcinoma. The tumor responded briefly to
      Cisplatinum, Vinblastine and Bleomycin (PVB) treatment. The patient died of brain
      metastasis and respiratory failure four months after starting systemic
      chemotherapy.

PMID- 1363397
TI  - Single lung transplantation for end-stage silicosis: report of a case. Lung
      Transplant Group.
AB  - After successful animal studies since 1986, a single left lung transplantation
      was performed on a 35-year-old male patient with end-stage silicosis in July
      1991. The surgical technique was similar to that used by the Toronto Transplant
      Group, except for some modification in bronchial anastomosis. The donor lung was
      preserved by simple surface cooling after the administration of heparin,
      methylprednisolone and PGE1. The ischemic time for the donor lung was 3.5 hours.
      A cardiopulmonary bypass through the femoral vessels was applied for a duration
      of 90 minutes. Immediate postoperative complications included massive bleeding,
      disseminated intravascular coagulation, adult respiratory distress syndrome and
      acute graft rejection. Fortunately, we overcame these complications through
      intensive care. Immunosuppression included antilymphocytic globulin,
      cyclosporine, azathioprine and corticosteroids. The results of this single lung
      transplantation were satisfactory. The patient was doing well and was able to
      satisfactorily breathe room air six weeks after the transplantation.
      Unfortunately, the patient died of opportunistic systemic aspergillosis six
      months after the transplantation. In conclusion, lung transplantation is an
      effective treatment for patients with end-stage lung diseases, and the results of
      this first single lung transplantation in Taiwan are encouraging and promising.

PMID- 1363399
TI  - [Scientific symposium: Progress in the diagnosis and therapy of bronchial asthma.
      Jachranka, 3-6 September 1992. Abstracts].

PMID- 1363398
TI  - Evaluation in vitro of T-cell mediated immunity in patients with atopic disease.
      Effects of thymic hormone therapy. II. Functional capacities of regulatory T
      lymphocytes. Total serum IgE levels. Clinical observation.

PMID- 1363400
TI  - Localization in situ of polyhomeotic transcripts in Drosophila embryos reveals
      spatially restricted expression beginning at the blastoderm stage.
AB  - Polyhomeotic is a member of a group of genes, the Pc-group responsible for the
      maintenance of gene expression during development. In particular, the Pc-group of
      genes is involved in the correct expression of homeotic genes of the bithorax and
      Antennapedia complexes. Molecular analysis reveals that the Pc-group genes
      function relatively late in development, once homeotic gene expression has been
      correctly initiated. This initiation of homeotic gene expression depends on
      interaction between genes in the segmentation gene hierarchy, the gap and pair
      rule genes. The in situ analysis presented here indicates that polyhomeotic
      transcripts are expressed in a spatially restricted fashion early in development.
      This blastoderm expression is under the control of genes in the segmentation
      hierarchy. Given these results, and the role of polyhomeotic in the correct
      maintenance of homeotic gene expression, I propose that polyhomeotic expression
      may relay the initiation of homeotic gene expression with other mechanisms
      involved in the maintenance of this expression, involving the other Pc-group
      genes.

PMID- 1363401
TI  - Cloning and sequence comparison of the mouse, human, and chicken engrailed genes
      reveal potential functional domains and regulatory regions.
AB  - We have isolated and characterized genomic DNA clones for the human and chicken
      homologues of the mouse En-1 and En-2 genes and determined the genomic structure
      and predicted protein sequences of both En genes in all three species. Comparison
      of these vertebrate En sequences with the Xenopus En-2 [Hemmati-Brivanlou et al.,
      1991) and invertebrate engrailed-like genes showed that the two previously
      identified highly conserved regions within the En protein ]reviewed in Joyner and
      Hanks, 1991] can be divided into five distinct subregions, designated EH1 to EH5.
      Sequences 5' and 3' to the predicted coding regions of the vertebrate En genes
      were also analyzed in an attempt to identify cis-acting DNA sequences important
      for the regulation of En gene expression. Considerable sequence similarity was
      found between the mouse and human homologues both within the putative 5' and 3'
      untranslated as well as 5' flanking regions. Between the mouse and Xenopus En-2
      genes, shorter stretches of sequence similarity were found within the 3'
      untranslated region. The 5' untranslated regions of the mouse, chicken and
      Xenopus En-2 genes, however, showed no similarly conserved stretches. In a
      preliminary analysis of the expression pattern of the human En genes, En-2
      protein and RNA were detected in the embryonic and adult cerebellum respectively
      and not in other tissues tested. These patterns are analogous to those seen in
      other vertebrates. Taken together these results further strengthen the suggestion
      that En gene function and regulation has been conserved throughout vertebrate
      evolution and, along with the five highly conserved regions within the En
      protein, raise an interesting question about the presence of conserved genetic
      pathways.

PMID- 1363402
TI  - Mutations in the glutamine synthetase I (gsI) gene produce embryo-lethal female
      sterility in Drosophila melanogaster.
AB  - A female-sterile mutation (fs(2) PM11-19) was recovered in a screen for P-M
      hybrid dysgenesis induced mutations uncovered by a deletion of region 21B and was
      identified as an allele of the gene encoding the Drosophila glutamine synthetase
      I (GSI) mitochondrial isozyme. Molecular analysis has shown that fs(2)PM11-19
      contains a 5 kb insert within 500 bp upstream of the transcriptional start site
      of the gsI gene. Mutant flies have extremely low levels of gsI transcription and
      GSI activity. A pre-existing deficiency (Df(2L) netPM1) with a breakpoint near
      the transcription start site was also found to be a female-sterile allele of gsI.
      All eggs laid by PM11-19 homozygous females, as well as by females heterozygous
      for this mutation and a deletion or any of several recessive lethal alleles of
      the gsI gene, fail to hatch. We conclude that an adequate level of maternally
      supplied GSI activity is necessary in the early stages of Drosophila embryonic
      development.

PMID- 1363403
TI  - Automated measurement of lactate dehydrogenase, alkaline phosphatase and gamma
      glutamyltransferase in urines: an alternative to the manual procedure.
AB  - A sensitive and precise automated assay of urinary lactate dehydrogenase (EC
      1.1.1.27), alkaline phosphatase (EC 3.1.3.1) and gamma-glutamyltransferase (EC
      2.3.2.2) is described. For this purpose, we used a BM/Hitachi System 704 model
      and reagents for automated analysis of serum enzymes from Boehringer Mannheim.
      However, the schedules of enzyme chemistry parameters recorded by the
      autoanalyzer and the spectrophotometric calibration are reprogrammed to meet
      requirements deriving from urine adoption and to optimize the enzyme assay in
      this unusual medium.

PMID- 1363404
TI  - More on effects of storage time and temperature on urinary enzymes: a 1-year
      study.
AB  - Results of our conclusive study on urinary enzyme stability during sample storage
      are reported. We measured alanine aminopeptidase (AAP) and N-acetyl-beta-D
      glucosaminidase (NAG) in morning urines from 9 healthy normal subjects
      immediately after collection and throughout a 1-year storage at -70 and -20
      degrees C. AAP proved to be quite stable at -70 degrees C (99.2% of the basal
      value at the end of the year). NAG is partially preserved (84.1% of the basal
      value) at -70 degrees C, but significantly decreased (50.4%) at -20 degrees C.

PMID- 1363405
TI  - [Comments on the section "Management of Injured Young Permanent Teeth" from the
      videotape recording "Dentistry Today"].

PMID- 1363407
TI  - Renal thromboxane A2 synthesis in the Lyon hypertensive rat.
AB  - The aim of the present study was to assess the mechanisms by which norepinephrine
      (NE) increased the synthesis of prostanoids and revealed a hyperactivity of the
      Thromboxane (Tx) A2 synthase in the Lyon genetically hypertensive (LH) rat
      kidney. To this purpose, the effects of NE (1.2 x 10(-8) to 9.6 x 10(-7) M) on
      renal function and prostanoid synthesis were assessed in isolated perfused
      kidneys following beta-adrenoceptor blockade by sotalol (10(-5)M) and compared to
      those of equipressor concentration of an alpha 2-adrenoceptor agonist, BHT 933
      (3.5 x 10(-4) M) and angiotensin II (AII) (7.7 x 10(-9) M). Kidneys were isolated
      from eight week-old male LH rats and from their normotensive (LN) and low blood
      pressure (LL) controls and perfused in a single pass system. In baseline
      conditions, sotalol did not modify renal function or urinary prostanoids in any
      of the three strains. Following NE stimulation, it potentiated the increase in
      renal vascular resistance of LL and LN controls but not that of LH rats. The
      pressure-natriuresis and the urinary prostanoids remained unchanged. BHT 933
      elicited a weak stimulation of prostanoid release while AII markedly increased it
      and revealed, as did NE, the hyperactivity of the TxA2 synthase. It is concluded
      that the NE-induced stimulation of prostanoid synthesis does not involve beta
      adrenoceptors and is unrelated to the associated hemodynamic changes. These
      results also demonstrate that the increased renal synthesis of TxA2 observed in
      LH rat kidney is not a specific response to alpha-adrenoceptor stimulation and is
      likely to involve activation of the phosphoinositide pathway.

PMID- 1363406
TI  - Immune response in intracranial tumours: a review.

PMID- 1363408
TI  - Oro-caecal transit time in man assessed by the sulfasalazine/sulfapyridine test.
      Correlation between plasma-saliva appearance of sulfapyridine.

PMID- 1363410
TI  - True hermaphroditism in 45,X/46,XY mosaicism.
AB  - This report discusses the clinical findings on two patients with 45,X/46,XY
      mosaicism, two boys presented with penile hypospadias and cryptorchidism. A
      dysgenetic ovary and a testis were found in one boy, and a dysgenetic ovary in
      the other. Both patients can be considered to be true hermaphrodites on the basis
      of histology and clinical and hormonal observations. 45,X/46,XY mosaics have a
      wide range of phenotypic appearances and their gonadal morphology can also show
      great differences. However, the incidence of true hermaphroditism in individuals
      with 45,X/46,XY mosaicism is low and the reports in the literature rare. It is
      likely that males with 45,X/46,XY who suffer only mild maldevelopment of the
      external genitalia will not be recognized. In all patients with penoscrotal
      hypospadias and cryptorchidism with 45,X/46,XY mosaicism, the possibility of true
      hermaphroditism should be considered.

PMID- 1363409
TI  - Acute effects of hydrocortisone on circulating growth hormone levels in patients
      with acromegaly.
AB  - Aim of our study was to investigate the acute effects of intravenous infusion of
      hydrocortisone on circulating growth hormone (GH) levels in acromegaly. We
      studied 5 adult patients with active acromegaly, 3 males and 2 females; age 52 +/
      3.6 years, body mass index 27 +/- 1 kg/m2. The patients underwent in randomized
      order from 0 to 120 min: (1) intravenous infusion of saline, 250 ml; (2) bolus
      intravenous injection of hydrocortisone succinate, 100 mg at time 0 followed by
      intravenous infusion of hydrocortisone succinate, 250 mg in 250 ml of saline for
      120 min. Blood samples for GH, cortisol and glucose assay were taken at -15, 0
      (time of beginning of saline or hydrocortisone infusion), 15, 30, 45, 60, 90,
      120, 150 and 180 min. In all the acromegalic patients, during hydrocortisone
      succinate infusion, GH values clearly fell with respect to saline (nadir range
      18.4-50.5% with respect to baseline levels) with nadir between 60 and 180 min
      after the beginning of the infusion. Our data show that acute and sustained
      hypercortisolism, decreases circulating GH levels in acromegaly. It seems likely
      that also in acromegalic patients as well as in normal subjects short-term
      increases in serum cortisol levels may be able to cause an enhancement of
      hypothalamic somatostatin secretion, which in turn may be responsible for the
      glucocorticoid-mediated GH inhibition.

PMID- 1363411
TI  - Multiple Endocrine Diseases: Growth Hormone Action: Intersexuality. Proceedings
      of the VIII International Symposium on Endocrinology and Development. Telfs,
      Austria, October 11-12, 1991.

PMID- 1363412
TI  - The genetics of multiple endocrine neoplasia (MEN).
AB  - Multiple Endocrine Neoplasia (MEN) refers to the family of diseases characterized
      by hyperplasia and/or tumoral proliferation in various organs derived from the
      neural crest. MEN are transmitted in an autosomal dominant fashion in affected
      pedigrees with a high degree of penetrance. MEN 1 and MEN 2A/B loci have recently
      been mapped, respectively, to chromosomes 11 and 10 by linkage analysis using
      polymorphic DNA markers. These discoveries will lead (1) to a rapid understanding
      of the physiopathological pathway determining such syndromes and (2) to major
      clinical impact through the genetic screening.

PMID- 1363413
TI  - Pathology of multiple endocrine neoplasias 2A and 2B: a review.
AB  - This review describes recent findings on the morphology, function and prognosis
      of lesions associated with the MEN 2 syndromes. Special emphasis is placed on the
      analogies and discrepancies between the hereditary and nonhereditary
      manifestations of the endocrine proliferations involved.

PMID- 1363414
TI  - Clinical features of multiple endocrine neoplasia type 1 and type 2.
AB  - The term 'Multiple Endocrine Neoplasia' (MEN) denotes a genetically determined
      syndrome characterized by the independent appearance of benign or malignant
      changes of several endocrine organs as well as occasional changes of neural,
      muscular and connective tissue. Three different forms have been identified: MEN 1
      (Werner's syndrome) includes parathyroid hyperplasia in combination with
      pancreatic islet cell and pituitary tumours; MEN 2a (Sipple's syndrome) includes
      medullary thyroid carcinoma in association with phaeochromocytoma and parathyroid
      hyperplasia; MEN 2b includes medullary thyroid carcinoma, phaeochromocytoma and
      mucosal neuromas. MEN syndrome is transmitted as an autosomal dominant trait with
      a high degree of penetrance. The changes in the individual glands appear to be
      causally and temporally independent of each other. A spectrum of pathological
      changes exist in the affected glands which range from hyperplasia to adenoma to
      carcinoma. The pathological process is almost always multicentric, often
      resulting in bilateral disease of organs. The appearance of an endocrine tumour
      known to be associated with MEN should alert the physician to the possibility of
      a MEN syndrome. When the possibility of such a syndrome exists, screening and
      long-term observation should be initiated to diagnose a carcinoma in its earliest
      stage, or before the development of clinical manifestations of hormone excess.

PMID- 1363415
TI  - Sensitivity of mosquito-pathogenic bacterial strains to various antibodies.
AB  - Four strains of Bacillus sphaericus, 1593, 2362, 9001 and 9002, B. thuringiensis
      H-14 and B. thuringiensis neoleonensis were tested for sensitivity against 18
      antibiotics. The results revealed that all the four strains of B. sphaericus are
      resistant to colistin, nalidixic acid, polymyxin B and streptomycin. However, B.
      thuringiensis H-14 was resistant to 9 antibiotics, viz. ampicillin, cephalexin,
      carbenicillin, co-trimoxazole, colistin, cloxacillin, penicillin, nitrofurantoin
      and polymyxin B whereas B. thuringiensis neoleonensis was found to be resistant
      to 8 antibiotics. These results may help in isolation of potential and resistant
      mosquito pathogenic bacteria.

PMID- 1363416
TI  - Immunization against Japanese encephalitis.

PMID- 1363417
TI  - Porphyria cutanea tarda and HIV infection: effect of zidovudine treatment on a
      patient.

PMID- 1363418
TI  - Genitourinary and sexual adverse effects of psychotropic medication.
AB  - OBJECTIVE: We review the adverse effects on genitourinary and sexual function
      associated with antidepressants, neuroleptics, lithium, and benzodiazepines, and
      suggest treatment strategies that may be used for their management. METHOD: This
      article is based on systematic review of the existing literature, including more
      than 130 relevant articles on genitourinary and sexual effects of psychotropic
      medications. RESULTS: We find that genitourinary function, including effects on
      continence and flow, and sexual function, including libido, erection, ejaculation
      and orgasm, may be altered by psychotropic administration. Many of these effects
      may be consequent to the impact of these medications on neurophysiologic systems.
      CONCLUSIONS: Genitourinary and sexual adverse effects associated with
      psychotropic therapy are important areas of study and clinical concern that may
      affect patient comfort and compliance with treatment.

PMID- 1363419
TI  - The expression of bipolar affective disorders in brain injured patients.
AB  - OBJECTIVE: A prospective study was designed to investigate the varied
      presentations of major affective disorders in patients with organic brain
      disease. METHOD: Patients admitted to our neuropsychiatry service, with affective
      and behavioral disturbances, and known neurological disorders, were classified,
      on phenomenological grounds, into the following groups: 1) elated mania; 2)
      irritable mania; 3) affective lability with periods of irritability, but without
      other symptoms pathognomonic for mania; and 4) intermittent psychosis with absent
      or ambiguous mood changes. RESULTS: A majority of patients in all four groups
      responded to pharmacotherapy with anti-cycling agents. CONCLUSIONS: It is
      proposed that these groups represent different expressions of mania in brain
      injured persons, and that these expressions range through a spectrum of
      phenomenology, included elated mania, irritable mania, episodic psychosis and
      explosive organic personality disorder. The DSM-III-R classification of these
      disorders, and approaches to their clinical management, are discussed.

PMID- 1363420
TI  - Interferon-gamma response region in the promoter of the class II MHC gene, DPA.
AB  - The class II MHC gene DPA is inducible by interferon-gamma (IFN-gamma), whereas
      the DQB gene is not inducible in most cell types. To investigate the DNA region
      specifically responsible for inducibility or its lack that may be required (in
      addition to the elements required for constitutive expression of class II genes),
      hybrid promoters were constructed between the proximal 5' regions of the DPA
      promoter up to -148 bp, which is IFN-gamma inducible, and of the DQB promoter up
      to -160 bp, which is not inducible. As a result of these and previous studies [9,
      10], the region of the DPA gene required for its IFN-gamma inducibility was
      localized to 27 bp between -55 and -81, including the Y-box element and its
      flanking nucleotides.

PMID- 1363421
TI  - HLA-A and DPB1 loci confer susceptibility to Graves' disease.
AB  - To investigate HLA-linked genetic factors involved in the pathogenesis of Graves'
      disease, 76 patients and 317 healthy controls in the Japanese population were
      examined for HLA-A, B, C, DR, and DQ specificities by serologic typing and for
      HLA-DPB1 alleles by DNA typing by using the PCR-SSOP method. The frequencies of
      HLA-A2, B46, Cw11, and DPB1*0501 were increased and those of HLA-A24, B7, Bw52,
      and DR1 were decreased in the patients. The increased frequencies of HLA-A2 and
      DPB1*0501 in the patients were statistically significant when the corrected p
      value (pc) was applied (pc < 0.02 and pc < 0.002, respectively). ORs for a risk
      to develop the disease were calculated among individuals positive for DPB1*0501
      and/or HLA-A2, and the highest OR (10.5) was observed in individuals possessed
      both DPB1*0501 and HLA-A2. This observation suggests a synergic involvement of a
      HLA class II allele (DPB1*0501) and an HLA class I allele (HLA-A2) in the
      pathogenesis of Graves' disease.

PMID- 1363423
TI  - Characterization of an HLA-DR15 DQ5 haplotype found in the Spanish Caucasoid
      population.
AB  - HLA class II typing by RFLP and PCR-SSOP has been performed on HLA-DR2-positive
      individuals as a part of a study on MHC in a Spanish Caucasoid population. The
      results of this study reveal that HLA-DR15 (DRB1*1501 DRB5*0101) and DQ5
      (DQA1*0102 DQB1*0501/0502) are not uncommonly associated in such a population.
      Family segregation has been assessed and allogeneic reactivity against some
      classic DR2 haplotypes has been tested; a stimulatory capability of DQ6 antigen
      in this situation is shown. It is suggested that the reported association is not
      uncommon in European Caucasoids as well as in other populations and it should be
      considered in matching for transplantation and in DR2-associated diseases.

PMID- 1363422
TI  - Sequencing and population analysis of four novel HLA-DPA1 alleles.
AB  - We determined the base sequences of the HLA-DPA1 gene from four B-lymphoblastoid
      cell lines (CB6B, LKT3, AMAI, and T7526) that showed distinct electrophoretic
      patterns of single-stranded polymerase chain reaction products of the HLA-DPA1
      gene. The novel HLA-DPA1 alleles of CB6B, LKT3, AMAI, and T7526 were designated
      DPA1*02021, DPA1*02022, DPA1*0301, and DPA1*0401, respectively. Although there
      was only one base substitution between DPA1*02021 and DPA1*02022, the single
      strand conformation polymorphism of these two alleles was clearly demonstrated by
      electrophoresis in a nondenaturing polyacrylamide gel containing 10% glycerol. In
      addition, we genotyped for the HLA-DPA1 gene of healthy unrelated Oriental
      individuals--i.e., 227 Japanese, 88 Papua New Guineans, and 41 Buyi-Chinese--to
      demonstrate the ethnic distribution of the HLA-DPA1 alleles.

PMID- 1363424
TI  - Laparoscopic cryptorchidectomy in horses.
AB  - Laparoscopic cryptorchidectomy was successfully performed in 15 standing or
      recumbent horses. In 3 horses, owners believed that castrations had been
      performed, but the horses had retained stallion-like behavior. Successful removal
      of undescended testes in these horses stopped this behavior. Laparoscopy offered
      excellent visualization of the structures of the vaginal ring and facilitated
      removal of the abdominally located testis. The internal and external inguinal
      rings were not invaded, thus the chance of serious complications that may result
      during open cryptorchidectomy procedures was minimized.

PMID- 1363425
TI  - Dysplastic nevus syndrome: melanoma-prone disease.
AB  - Regardless of subsequent clinical courses of patients with dysplastic nevi (DN),
      substantial evidence supporting DN as one of the melanoma-prone diseases is not
      yet available, especially in sporadic DN, due to the lack of genetic information
      other than retrospective studies in clinical observation. This study aimed at the
      immunohistological characterization of sporadic DN distinct from common nevi (CN)
      and at the evaluation of the potentially of sporadic DN for malignant
      transformation. We considered our results together with previous immunological
      and epidemiological reports. We noted the following three immunohistological
      characteristics. 1) Proliferating cell nuclear antigen (PCNA), one of the markers
      for active cell division, could be detected on DN cells in junctional nests of
      only one among ten DN examined but not on CN cells at all. 2) The altered
      expression of alpha-smooth muscle actin (alpha-Sma), often observed in melanoma
      cells, could not be detected in DN cells. However, anti-alpha-Sma monoclonal
      antibody (MoAb) clearly demonstrated distinctive hypervascularity in the stroma
      surrounding DN when compared with CN. 3) ME491 antigen, which is known to be
      expressed mainly in the radial growth phase of melanoma, was detected with
      similar intensity on both DN and CN. These data indicate that DN has a somewhat
      higher potentiality than CN for cell division and secretion of some cytokines
      which can induce hypervascularity in the surrounding stroma, but that DN has not
      yet undergone the significant phenotypic changes observed in melanoma cells.
      Further advancements in understanding molecular events in DN cells will be of
      great benefit in setting DN in the multiple oncogenic spectrum from pigment cells
      to melanoma.

PMID- 1363426
TI  - The interaction between Langerhans cells and CD4+ T cells.
AB  - The human skin is increasingly exposed to haptens and environmental protein
      antigens. Because Langerhans cells represent the outermost network of MHC class
      II+ antigen presenting cells in mammalians, we investigated their interaction
      with CD4+ T cells. Hapten-modified Langerhans cells induced proliferation and IL
      2 production in naive resting CD4+ T cells. T cells activated in this manner and
      subsequently cultured with IL-2 mediated contact sensitivity in vivo and produced
      IL-2 but no IL-4 upon restimulation in vitro. Thus they corresponded to Th1
      cells. Repeated stimulation with Langerhans cells induced a modulation of the
      lymphokine pattern: IL-2- and IL-4-producing Th0-like cells were identified after
      3 to 4 rounds of restimulation; after > 5 rounds, Th2-like cells with an IL-4+IL
      2- pattern and the capacity for inducing IgE synthesis in B cells was identified.
      Th2 cells were also recently found to mediate inflammatory tissue lesions
      containing a cellular infiltrate. This demonstrates that Langerhans cells may
      activate resting CD4+ T cells, Th1-, Th0- and Th2-like cells. It further shows
      that Langerhans cells may promote the differentiation of postthymic CD4+ T cells
      into subsets with distinct immune functions: Th1 cells which have the potential
      to mediate inflammatory reactions such as allergic contact sensitivity and Th2
      cells which may be responsible for abnormalities associated with atopic
      dermatitis, such as elevated IgE and inflammatory skin lesions containing a
      cellular infiltrate.

PMID- 1363427
TI  - The interaction between keratinocytes and T cells--an overview of the role of
      adhesion molecules and the characterization of epidermal T cells.

PMID- 1363428
TI  - The cornified cell envelope: loricrin and transglutaminases.
AB  - The cornified cell envelope (CE) of terminally differentiated human epidermis is
      a complex structure consisting of several defined protein constituents. The CE is
      the most insoluble component of the epidermis due to crosslinking by disulfide
      bonds as well as isodipeptide bonds that are formed by the action of
      transglutaminases (TGases). We have recently determined that loricrin is the
      major component of CE. We now have isolated and characterized its gene and showed
      that it has a simple structure with a single intron. We also show that the
      loricrin gene maps to position 1q21, which, coincidentally, is similar to the
      location of the profilaggrin and involucrin genes. Human loricrin in 26 kDa and
      consists of three long glycine-serine-cysteine rich sequence domains that contain
      quasi-repeating peptides and which form the novel glycine loop motif. These are
      interspersed by lysine+glutamine rich domains involved in isodipeptide
      crosslinks. The glycine loops are thought to be involved in organization of
      epidermal proteins and maintenance of the flexibility of the epidermis. By use of
      PCR analyses, we have found that human loricrin consists of two allelic size
      variants, due to sequence variations in the second glycine loop domain only, and
      these variants segregate in the human population by normal Mendelian mechanisms.
      Furthermore, there are multiple sequence variants within these two size class
      alleles due to various deletions of 12 bp (4 amino acids) in the major loop of
      this glycine loop domain. In order to study the expression and role of TGases in
      the formation of CE, we have isolated and sequenced cDNA and genomic clones
      encoding the TGase1 enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363429
TI  - Alteration of melanoma melanogenesis by phenotypic modifiers.
AB  - Human melanoma cells (MM96E) were incubated with a phenotypic modifier (L
      ethionine) to compare its effects on phenotypic expression with those induced by
      sodium butyrate and dimethyl sulfoxide. In contrast to the latter agents, L
      ethionine (8mM) failed to arrest the cell cycle at the G1 phase or to inhibit
      colony formation ability after 48 hr incubation. Tyrosinase activity changed in
      parallel with 5-S-cysteinyldopa (5-S-CD) content during treatment with sodium
      butyrate or dimethyl sulfoxide. Tyrosinase was inhibited in L-ethionine-treated
      cells, probably because of metabolism of L-ethionine to sulfhydryl compounds;
      this remains to be clarified. Gamma-glutamyl transpeptidase activity changed
      inversely with tyrosinase activity after sodium butyrate or dimethyl sulfoxide
      incubation, whereas L-ethionine did not significantly alter the enzyme activity.
      In addition, only sodium butyrate induced alkaline phosphatase activity. L
      ethionine was less effective than sodium butyrate or dimethyl sulfoxide in
      inhibiting expression of the B8G3 melanosomal antigen, as determined by Western
      blotting. These results suggest that phenotypic modifiers (differentiation
      inducers) affect melanoma cells in various ways and that melanogenesis therefore
      reflects only one aspect of differentiation in pigment cells.

PMID- 1363430
TI  - Comparison of restriction fragment length polymorphisms of ribosomal DNA between
      Diphyllobothrium nihonkaiense and D. latum.
AB  - Restriction fragment length polymorphisms (RFLPs) of ribosomal DNA (rDNA) were
      compared between Diphyllobothrium latum and D. nihonkaiense using seven kinds of
      restriction endonucleases. No intra-specific variation in restriction fragment
      profiles was shown within both species of Diphyllobothrium. Digestion of the
      genomic DNA with three endonucleases. SmaI, HinfI and HhaI, provided one or two
      different bands between two species, although the hybridization patterns
      generated with the others. HindIII, XbaI, StyI and HaeIII, were the same in both.
      RFLPs in the digested profiles with SmaI, HinfI and HhaI could be used as species
      specific markers even if only fragments of strobilae with morphological
      similarity were available. Other cestodes, Spirometra erinacei and Taenia
      saginata, used as controls showed quite different restriction fragment patterns
      with all the enzymes used.

PMID- 1363431
TI  - Indoor Air '90: the 5th in a series of international conferences on the indoor
      environment.
AB  - The 5th International Conference on Indoor Air Quality and Climate: INDOOR AIR
      '90 continued a series of international scientific conferences begun in 1978 on a
      complex, interdisciplinary subject increasingly recognized to be of importance to
      human comfort, health and productivity, and having important implications for
      building design and furnishing, office equipment, appliances, cleaning, heating,
      ventilating, humidifying and air-conditioning. INDOOR AIR '90 constituted a week
      long program of 542 paper and poster presentations and forum discussions, 100
      exhibits, and a public forum. This paper summarizes some of the highlights of
      this conference and links these to some of the studies reported at earlier INDOOR
      AIR Conference.

PMID- 1363432
TI  - Bradykinin metabolism pathway in the rat pulmonary circulation.
AB  - OBJECTIVE: The contribution made by different enzymes to the degradation of
      bradykinin in physiological conditions was estimated by examining bradykinin
      metabolism in rat serum, in the in situ perfused lung and in vivo. METHODS: Dose
      response curves for the hypotensive effect of intra-arterially and intravenously
      injected bradykinin were obtained in unanaesthetized rats. High-performance
      liquid chromatography was used to analyse the products of bradykinin breakdown
      after incubation with rat serum and perfusion through in situ lung preparations.
      RESULTS: In rat serum, kininase I degraded 34% and kininase II 11% of bradykinin,
      no evidence for other activities being detected. In the awake rat, D,L-2
      mercaptomethyl-3-guanidino-ethylthiopropionic acid, an inhibitor of kininase I,
      did not reduce the percentage of bradykinin inactivation in the pulmonary
      circulation. In the in situ perfused lung 65% of bradykinin was metabolized and
      the main products were BK1-7, BK1-5 and BK4-9. Enalaprilat (an inhibitor of
      kininase II) blocked the formation of BK1-7 and BK1-5 and increased the recovery
      of BK4-9. beta-Mercapto-ethanol, which inhibits aminopeptidase P, and diprotin A,
      a specific inhibitor of dipeptidylaminopeptidase IV, both reduced the formation
      of BK4-9. Diprotin A also allowed the recovery of BK2-9. Bradykinin degradation
      and BK4-9 recovery were not affected by endopeptidase inhibitors. CONCLUSIONS:
      Our results show that the main degradation pathway of bradykinin in the lung is
      through the action of kininase II at the carboxyl terminus, and sequential
      cleavage by aminopeptidase P followed by dipeptidylaminopeptidase IV at the amino
      terminus. The amino-terminal degradation of bradykinin represents about 38% of
      the total lung kininase activity.

PMID- 1363433
TI  - Pulmonary kinin metabolism and conversion of angiotensin I in spontaneously
      hypertensive rats.
AB  - OBJECTIVE: To examine the metabolism of kinins and angiotensin I in the pulmonary
      circulation of spontaneously hypertensive rats (SHR) and normotensive Wistar rats
      (NWR). METHODS: Bradykinin inactivation was estimated in vivo by comparison of
      the hypotensive effect of intra-arterial and intravenous injections, and in the
      in situ perfused lung by analysing the breakdown products using high-performance
      liquid chromatography. RESULTS: In vivo pulmonary degradation of bradykinin, but
      not that of higher homologues of this peptide, was shown to be significantly
      greater in SHR. Angiotensin I converting activity was found to be increased in
      lungs of SHR. The recovery of bradykinin and homologues from perfused SHR lung
      was decreased relative to NWR. Des-(Phe-Arg) fragments of all kinin analogues
      were identified in the pulmonary perfusates. When bradykinin and des-Arg9
      bradykinin were injected in the perfused lungs, the respective fragments 4-9 and
      4-8 were also identified in the perfusates. When kininase II was inhibited with
      enalaprilat, the recovery of bradykinin increased from 10 to 43% in SHR and from
      23 to 58% in NWR, whereas about 90% of the higher bradykinin homologues were
      recovered in both SHR and NWR. Aminopeptidase P and dipeptidylaminopeptidase IV,
      as measured by the recovery of fragment 4-9 under kininase II inhibition,
      accounted for about 40% of the total pulmonary kininase activity in the SHR lungs
      and 25% of that of the NWR lungs. CONCLUSIONS: The results show that SHR have
      increased kininase and angiotensin converting activity compared with NWR, and
      that kinins as well as angiotensin may contribute to the pathogenesis of
      hypertension. Aminopeptidase P and dipeptidylaminopeptidase IV may contribute to
      the increased in vivo degradation of bradykinin observed in the SHR.

PMID- 1363434
TI  - [Current alteration of Helicobacter pylori in gastro-duodenal diseases].
AB  - The current alteration of the detection rate of Helicobacter pylori (H. pylori)
      on mucous membranes of the stomach has been surveyed and reviewed for 49 cases of
      gastro-duodenal diseases. The survey has been conducted for 3 years and an
      endoscopic examinations have been performed 2-8 times. On the first visit, the
      diagnosis can be made endoscopically, and H2 blockers and another agents were
      used as therapeutic drugs. The detection rate was 67.3% (33 cases) for positive
      cases and positive reaction cases, while the rate was 32.6% (16 cases) in
      negative cases and negative reaction cases. Among them, the most commonly
      observed disease was atrophic gastritis, followed by duodenal ulcer, and acute
      gastric mucous lesions (AGML). Peptic ulcer was not seen. After administration of
      H2 blockers and anti-ulcer agents, the H. pylori-detection rate was found to
      fluctuate according to the diseases and alterations in the morbidity period. Some
      cases indicated the disappearance of H. pylori in accordance with the improvement
      of the lesion site.

PMID- 1363435
TI  - [A study to clarify the mechanism of the usefulness of the macrolides--the
      influence of clarithromycin to biofilm with P. aeruginosa].
AB  - Clarithromycin (CAM) was administered long-term to patients with diffuse
      panbronchiolitis (DPB) to clarify the mechanism of the usefulness of the
      macrolides (MLs). 1. A tendency for clinical improvement was observed in 17
      patients with DPB. Bacteria were eradicated in 7 of 9 patients with P. aeruginosa
      found in sputum. 2. A biofilm experimental model with P. aeruginosa was found to
      be destructed through constant contact with CAM and formed into a single cell
      with a smooth surface. 3. It was believed that the new lesion forming capability
      of P. aeruginosa that had been in contact with CAM was reduced due to a
      significant decrease in adherence to tissue. P. aeruginosa was principally
      eradicated by the host factors. These results suggested that the improvement in
      the prognosis of DPB with P. aeruginosa in the sputum after adding MLs was
      closely related to the destructive effect of the MLs on the biofilm.

PMID- 1363437
TI  - [Left ventricular diastolic dysfunction in ischemic heart disease. Effects of
      drug therapy].

PMID- 1363439
TI  - [Wound healing. European Congress of Wound Healing and Skin Physiology].

PMID- 1363438
TI  - [Forum medical--enterostomy therapy. A possibility for the further qualification
      of stoma therapists].

PMID- 1363436
TI  - Calcium current modulation in frog sympathetic neurones: L-current is relatively
      insensitive to neurotransmitters.
AB  - 1. Neurotransmitters (noradrenaline, NA; chicken II luteinizing hormone-releasing
      hormone, LHRH) and activators of G proteins (GTP-gamma-S and AlF3) partially
      inhibit calcium current in bullfrog sympathetic neruones. Activation of the
      remaining current is slowed and shifted to more positive voltages. 2. The N-type
      calcium current appears to be the type modulated, since approximately 90% of peak
      current is blocked by omega-conotoxin (omega CgTx) and modulation is not affected
      by nisoldipine. 3. Calcium current at relatively negative voltages (-30 to -50
      mV) is resistant to transmitter modulation. The current at such voltages is also
      resistant to omega CgTx, suggesting that it results from a different type of
      calcium channel. 4. The omega CgTx-resistant current includes dihydropyridine
      (DHP)-sensitive and DHP-resistant components. The omega CgTx- and DHP-resistant
      current is inhibited by transmitter agonist, but the DHP-sensitive (L-type)
      current is not. 5. In cells dialysed with a low concentration of calcium buffer
      (0.1 mM-BAPTA), transmitters still inhibit N-current incompletely. However, L
      current was partially inhibited (approximately 10%) by LHRH, NA and the
      muscarinic agonist oxotremorine-M (OXO-M).

PMID- 1363441
TI  - [Medical Physics-93. 2nd conference of the Association of Medical Physicists of
      the Physics Society of Russia. February 1993. Abstracts].

PMID- 1363440
TI  - Oral vitamin B12 treatment of cobalamin-responsive methylmalonic aciduria.

PMID- 1363442
TI  - [Recent advances in the etiopathology of chronic B-lymphocytic leukemia].
AB  - Considerations to multistep development of B-lymphocytic chronic leukaemia are
      presented under the following aspects: experimental in vitro cultures of bone
      marrows B lymphocyte precursors, polyclonal nature of proliferating B lymphocytes
      in the early stage of CLL, especially in the autoimmune status, the role of
      viruses, the effect of nonrandom chromosome abnormalities and associated
      alterations in gene functions, clonal evolution during terminal stages of CLL.

PMID- 1363444
TI  - [News of a congress: 1st European congress of nursing schools].

PMID- 1363443
TI  - Clinical predictors of 1-year outcome in schizophrenia.
AB  - To assess clinical predictors of 1-year outcome in schizophrenia, 63 patients
      were studied prospectively. Persistent negative and total symptoms after 4 weeks
      of neuroleptic treatment accounted for 62% of the variance of 1-year outcome,
      whereas baseline measures showed no relationship to outcome. Thus, 1-year outcome
      in schizophrenia can be reasonably predicted on the basis of symptoms persisting
      after 4 weeks of treatment.

PMID- 1363446
TI  - Operational Research in Health Projects. Proceedings from the 7th Symposium of
      the Working Group on Interdisciplinary Research in Tropical Medicine. Heidelberg,
      28-29 February 1992. Abstracts.

PMID- 1363445
TI  - Evaluation of the residual efficacy of permethrin-impregnated screens used
      against mosquitoes in Marigat, Baringo district, Kenya.
AB  - Insecticide-impregnated screens and bednets are gradually finding wider use in
      malaria control programmes. The efficacy of these devices is dependent on the
      method of application, the acceptability by the people and effectiveness of the
      insecticide used. The present studies were carried out to determine the duration
      of the effectiveness of a permethrin-impregnated wall cloth (Mbu cloth) used in
      the Marigat area of Baringo District, Kenya in order to ensure its effective use.
      Cotton cloth impregnated with permethrin was hung inside an experimental house in
      Marigat and small pieces cut off each month for bioassay against mosquitoes over
      a twelve month period. The wall cloth remained effective for 6, 4 and 10 months
      against Anopheles gambiae s.l. the known vector of malaria, Culex quinque
      fasciatus and Aedes aegypti, respectively.

PMID- 1363447
TI  - [Role of N-methyl-D-aspartate receptor in the maintenance of learning-dependent
      long-term potentiation in rat hippocampal CA3 area].
AB  - The effect of microinjection of 2-amino-5-phosphonovaleric acid (APV), a
      selective NMDA receptor antagonist, into the rat hippocampal CA3 area on the
      synaptic efficacy and related conditioned behavior during the acquisition and
      consolidation of discrimination learning behavior was examined. The results
      showed: (1) After population spike (PS) amplitude had just increased to the
      maximum through training i.e. learning-dependent LTP had just formed, APV 1
      microliter (2 mmol/L) was injected into CA3 area, then the rats were trained
      during the time of efficacy of the drug in every experimental block. The result
      demonstrated that the PS amplitude could not be maintained at the highest level
      but decreased to the pre-experiment level after 8 blocks. Correct response
      percentage of rats could not be consolidated with further training but decreased
      to less than 10%. (2) After the PS amplitude had kept up at the highest level,
      APV 1 microliter (2 mmol/L) was injected into CA3 area, then the rats were
      trained during the time of efficacy of the drug in every experimental block, in
      which case the PS amplitude also could not be maintained at the highest level but
      decreased to the pre-experiment level after 14 blocks. Correlatively, when the
      correct response percentage of rats decreased gradually to less than 10%, the
      conditioned response of the animals extinguished, but its extinction speed was
      slower than it was in result (1). These results suggest that the NMDA receptor in
      CA3 area plays an important role in the maintenance of the learning-dependent
      long-term potentiation.

PMID- 1363448
TI  - [Radiation lesions, their medical sequelae and the possibilities for individual
      protection (based on materials from a conference held in Moscow 20-21 November
      1991)].

PMID- 1363449
TI  - [Periarteritis nodosa and an infection with the hepatitis B virus].

PMID- 1363450
TI  - [The activity of lipid peroxidation processes and the status of the neurohumoral
      regulation mechanisms in patients with chronic pyelonephritis].

PMID- 1363451
TI  - Unravelling the paradox.

PMID- 1363452
TI  - Cloning and disruption of a gene required for growth on acetate but not on
      ethanol: the acetyl-coenzyme A synthetase gene of Saccharomyces cerevisiae.
AB  - A DNA fragment of Saccharomyces cerevisiae with high homology to the acetyl
      coenzyme A (acetyl-CoA) synthetase genes of Aspergillus nidulans and Neurospora
      crassa has been cloned, sequenced and mapped to chromosome I. It contains an open
      reading frame of 2139 nucleotides, encoding a predicted gene product of 79.2 kDa.
      In contrast to its ascomycete homologs, there are no introns in the coding
      sequence. The first ATG codon of the open reading frame is in an unusual context
      for a translational start site, while the next ATG, 24 codons downstream, is in a
      more conventional context. Possible implications of two alternative translational
      start sites for the cellular localization of the enzyme are discussed. A stable
      mutant of this gene, obtained by the gene disruption technique, had the same low
      basal activity of acetyl-CoA synthetase as wild-type cells when grown on glucose
      but completely lacked the strong increase in activity upon entering the
      stationary phase, providing direct proof that the gene encodes an inducible
      acetyl-CoA synthetase (ACS1) of yeast. As expected, the mutant was unable to grow
      on acetate as sole carbon source. Nevertheless, it showed normal induction of
      isocitrate lyase on acetate media, indicating that activity of acetyl-CoA
      synthetase is dispensable for induction of the glyoxylate cycle in S. cerevisiae.
      Surprisingly, disruption of the ACS1 gene did not affect growth on media
      containing ethanol as the sole carbon source, demonstrating that there are
      alternative pathways leading to acetyl-CoA under these conditions.

PMID- 1363454
TI  - [Autologous blood-derived stem cell transplantation in the treatment of
      hematopoietic malignant diseases (Part II)].
AB  - Autologous transplantation of circulating stem cells is potentially capable of
      creating a chance of normal hematopoietic reconstitution in the patients in which
      both allogeneic and autologous bone marrow transplantation was impossible. The
      authors have reviewed the possibilities for collection of adequate and sufficient
      numbers of peripheral blood stem cells as well as up-to-date results of their
      autografting especially in relation to hematopoietic malignant diseases. The
      advantages resulting from autologous transplantation of circulating stem cells
      depends on: 1. The lack of risk of GvH--disease. 2. early and rapid hematopoietic
      and lymphoid recovery, 3. probably, the low risk of graft contamination by tumor
      cells in early remission.

PMID- 1363453
TI  - Purification of rat liver arylsulfatase A and its microheterogeneity assayed by
      crossed affinity-immunoelectrophoresis.
AB  - Arylsulfatase A (arylsulfatase sulfohydrolase) EC 3.1.6.1 was purified from rat
      liver by a procedure consisting of differential centrifugation, Con A-Sepharose
      and Blue Sepharose chromatography, PBE 94 chromatofocusing, DEAE-cellulose and
      gel filtration chromatography followed by preparative electrophoresis. A
      molecular mass of 132,000 was estimated by gradient PAGE. Particular proteins
      were detected by immunoelectrophoresis. Isoelectric focusing combined with
      immunoelectrophoresis gave two peaks of arylsulfatase A, with isoelectric points
      of pH 3.9 and 4.5. Microheterogeneity of rat liver arylsulfatase A was studied by
      affinity immunoelectrophoresis with 9 different lectins. The presence of
      concanavalin A-, Lens culinaris agglutinin-, Lotus tetragonolobus agglutinin- and
      wheat germ agglutinin-reactive forms permitted assessment of the types of
      carbohydrate moieties in arylsulfatase A.

PMID- 1363455
TI  - Transient eosinophilia in a patient with hairy-cell leukaemia treated with 2
      chlorodeoxyadenosine.
AB  - Eosinophilia may be associated with various pathologic states such as malignant
      disorders, atopic and parasitic diseases, certain infections, as well as drug
      reactions. We describe a case of a 48-year-old patient who was submitted to a
      single-course therapy with 2-chlorodeoxyadenosine because of hairy-cell leukaemia
      and previously did not respond to splenectomy. After the treatment marked
      transient eosinophilia appeared which preceded the achievement of complete
      remission. It is supposed that eosinophilia might have been caused by the release
      of cytokines from damaged leukaemic cells.

PMID- 1363456
TI  - [Synthesis and pharmacological activities of the 1-substituted 4-methoxycarbonyl
      fentanyl derivatives].
AB  - Five derivatives of 4-methoxycarbonyl fentanyl were synthesized, four of them
      carry in the molecules some radicals that may alkylate opiate receptors. Their
      analgesic activities were measured and the irreversible inhibitory effects of all
      compounds on the electrically elicited contraction of MVD were investigated. The
      analgesic test showed that the compounds in this series possess analgesic
      activity with typical morphine--like action. The isolated tissue experiment
      indicated that these new compounds were all capable of binding with opiate
      receptors, and that compounds 2, 4 and 5 were determined to be a new irreversible
      ligand of opiate receptors.

PMID- 1363457
TI  - Long-term treatment with carbamazepine affects CSF somatostatin immunoreactivity
      in epileptic patients.
AB  - A number of pharmacological evidence supports the view that somatostatin (SS) may
      be importantly involved in the seizure susceptibility both in humans and in
      laboratory animals. In a previous report the Authors have provided the finding
      that a short-term carbamazepine (CBZ) administration is able to reduce SS-CSF-IR
      in epileptic patients. The present study has been carried out to investigate
      whether a long-term treatment with CBZ affects in a similar way SS-IR content in
      CSF from temporal lobe epileptics (CPS). The results confirm and expand previous
      evidence suggesting that CBZ lowering effect on CSF-SS-IR may be relevant to its
      anticonvulsivant action.

PMID- 1363458
TI  - Friedreich's disease. A linkage study in southern and central Italy.
AB  - We studied linkage and linkage disequilibrium between the genetic locus of
      Friedreich's disease (FRDA) and two maker loci (D9S15 and D9S5) of chromosome
      9q13-q21.1 in 49 subjects from 12 families in southern and central Italy. No
      recombination event occurred between D9S15 and D9S5, or between these
      polymorphisms and FRDA. Linkage disequilibrium was not observed between D9S15 or
      D9S5 or the extended haplotypes and FRDA, but was present between the two
      polymorphisms.

PMID- 1363459
TI  - Genetic linkage analysis and presymptomatic testing in Huntington's disease.
      First report in Italy.
AB  - Since 1979 data about Huntington's Disease (HD) in Campania, a region of Southern
      Italy, has been collecting. The prevalence of HD in this sample is 30.3 x 10(-6)
      (115 pedigrees, 1470 individuals). Mean age at onset was 38.67 years and the
      juvenile (onset before 20 years) accounted for 5.8%. Genetic linkage analysis in
      4 unrelated pedigrees with D4S10 and D4S95 DNA probes has been performed. The
      absence of genetic heterogeneity--already proposed in a cooperative study for one
      pedigree--has been confirmed in this study.

PMID- 1363461
TI  - Synthesis and H2-antagonist properties of some 1,2,5-thiadiazole-1-oxide
      derivatives.
AB  - A series of 1,2,5-thiadiazole-1-oxide derivatives has been synthesized and
      studied for its H2-antagonist properties. These derivatives can be considered
      derived from classical H2-antagonists in which the structure was deeply modified
      in order to evidence the minimal structural requirements for the activity. It was
      found that it is sufficient to have the 1,2,5-thiadiazole-1-oxide ring
      substituted with an alkylamino moiety and with an aliphatic chain linked to the
      hydroxy or ether group to achieve compounds as active as cimetidine. A few
      considerations on the binding on guinea-pig cerebral cortex of a series of H2
      antagonists with more and more simplified structures are also reported.

PMID- 1363460
TI  - Proliferative activity of cutaneous melanocytic neoplasms defined by a
      proliferating cell nuclear antigen labelling index.
AB  - To evaluate the proliferative activity of benign, borderline and malignant
      cutaneous melanocytic neoplasms, 30 cases of malignant melanoma (MM) and 41 cases
      of naevi were studied by immunostaining using a monoclonal antibody against
      proliferating cell nuclear antigen (PCNA). PCNA is a nuclear antigen expressed in
      the late G1 and S phase and serves as a marker of proliferating cells. Invasive
      MM and MM in situ showed much higher PCNA positivity rates than melanocytic naevi
      (invasive MM, 18.0%; MM in situ, 11.3%; ordinary melanocytic naevi, 2.6%). The
      PCNA positivity rate did not increase significantly with the thickness of MM.
      Among ordinary melanocytic naevi, junctional naevi had a higher PCNA positivity
      rate than compound or intradermal naevi. Mean PCNA positivity rates for Spitz's
      naevi and sporadic dysplastic naevi were within the range for ordinary
      melanocytic naevi, indicating the benign nature of both types of naevus. Contrary
      to some previous studies, MM in situ showed high proliferative activity,
      indicating that cells of MM in situ are actively proliferating. This study
      clearly demonstrates that MM and various types of naevi can be separated
      according to differences in proliferative activity defined by the PCNA labeling
      index.

PMID- 1363462
TI  - Prodrugs of peptides. 19. Protection of the pyroglutamyl residue against
      pyroglutamyl aminopeptidase by N-acyloxymethylation and other means.
AB  - The N-terminal pyroglutamyl group in several peptides is specifically cleaved by
      pyroglutamyl aminopeptidase (PAPase I). With the aim of protecting this group
      against enzymatic cleavage by the prodrug approach, various derivatives of L
      pyroglutamyl benzylamide, used as a PAPase I sensitive model pyroglutamyl
      peptide, were prepared and their stability characteristics determined. The
      derivatives studied included phenoxycarbonyl, phthalidyl, hydroxymethyl and
      actoxymethyl derivatives, all formed at the pyroglutamyl NH-moiety. Whereas L
      pyroglutamyl benzylamide was rapidly hydrolyzed by PAPase I, all the derivatives
      were resistant to cleavage by the enzyme. On the other hand, these derivatives,
      with the exception of the N-phenoxycarbonyl derivative, were readily converted to
      the parent pyroglutamyl benzylamide by spontaneous or plasma catalyzed
      hydrolysis, the half-lives of conversion in 80% human plasma being in the range
      2.3-8.4 h. The major degradation reaction of the N-phenoxycarbonyl derivative in
      both buffer and plasma solutions was hydrolytic opening of the pyrrolidone ring.
      The pH-rate profiles for the degradation of the compounds in aqueous solution
      were obtained and both specific acid and base catalytic reactions as well as a
      spontaneous reaction were observed. The results suggest that N-phthalidylation, N
      hydroxymethylation and N-acyloxymethylation of pyroglutamyl peptides may be
      useful prodrug approaches to protect such peptides against cleavage by
      pyroglutamyl aminopeptidase and hence to improve their delivery characteristics.

PMID- 1363463
TI  - Comparison of CD3 and CD2 activation pathways in T cells from young and elderly
      adults.
AB  - The ability of purified T cells to be activated by immobilized anti-CD3 and
      soluble anti-CD2 monoclonal antibodies (mAbs) was compared using cells from young
      and old donors. Purified T cells from elderly humans activated with immobilized
      anti-CD3 mAb incorporated less [3H]thymidine (58,780 vs 92,258 cpm; p < 0.02)
      into cellular DNA, and secreted less IL-2 into the culture supernatants than did
      T cells from young donors. In contrast, T cells activated with anti-CD2 mAbs
      displayed no age-related differences in proliferation or IL-2 production. Anti
      CD2 stimulation resulted in equal IL-2 synthesis by cells from young and old
      donors that was comparable to the amount produced by cells from elderly donors
      stimulated with immobilized anti-CD3. Northern blot analysis of early cell cycle
      gene expression by anti-CD2 activated T cells demonstrated no age differences in
      the expression of p55 IL-2R or c-myc specific mRNA, although T cells from elderly
      individuals activated with immobilized anti-CD3 showed statistically significant
      decreases in both mRNAs. T cell receptor beta chain mRNA levels did not differ
      between cells from young or old donors after activation by either anti-CD3 or
      anti-CD2. The discordance in proliferative ability, IL-2 secretion, and specific
      mRNA expression between T cells from elderly donors activated through the CD3-TCR
      complex or by soluble anti-CD2 mAbs provides additional evidence for a
      multifactorial causation of age-related T cell proliferative defects, and may
      indicate that the difference in proliferative ability is, in part, attributable
      to responsiveness to secreted IL-2.

PMID- 1363464
TI  - [Functionally important residues of glutamic acid in E. coli pyrophosphatase. I.
      Chemical modification and localization in the primary structure].
AB  - Inorganic pyrophosphatase of E. coli is rapidly and irreversibly inactivated by 5
      ethyl-5-phenylisoxazolium-3'-sulfonate (Woodward's reagent K). The appearance in
      the absorption spectrum of a maximum at 340 nm testifies to the formation of an
      enzyme enol ester with the inhibitor. The non-hydrolyzable substrate analog CaPP1
      partly protects the enzyme from inactivation. A peptide has been isolated from a
      tryptic hydrolysate of inactivated enzyme which contains an amino acid residue
      whose modification is critical for the enzyme activity. This peptide corresponds
      to residues 95-104 of pyrophosphatase and contains four dicarboxylic acid
      residues. A peptide containing a modified glutamic acid residue was isolated from
      modified pyrophosphatase hydrolyzed by protease v8. This peptide represents a
      fragment of a tryptic modified peptide and has a Glu-Ala-Gly-Glu (residues 98
      1C1) structure. It is concluded that inactivation of E. coli pyrophosphatase by
      Woodward's reagent K is a result of selective modification of Glu98, apparently
      by the most reactive dicarboxylic amino acid within the enzyme active center.

PMID- 1363465
TI  - Thunberginols C, D, and E, new antiallergic and antimicrobial
      dihydroisocoumarins, and thunberginol G 3'-O-glucoside and (-)-hydrangenol 4'-O
      glucoside, new dihydroisocoumarin glycosides, from Hydrangeae Dulcis Folium.
AB  - New antiallergic and antimicrobial dihydroisocoumarins, thunberginols C, D, and
      E, were isolated from Hydrangeae Dulcis Folium, the fermented and dried leaves of
      Hydrangea macrophylla SERINGE var. thunbergii MAKINO, together with new
      dihydroisocoumarin glycosides, thunberginol G 3'-O-glucoside and (-)-hydrangenol
      4'-O-glucoside. Their chemical structures have been determined on the basis of
      chemical and physicochemical evidence. Thunberginols C, D, E, G, and (-)
      hydrangenol 4'-O-glucoside showed antiallergic activity in the in vitro bioassay
      using the Schults-Dale reaction in sensitized guinea pig bronchial muscle, and
      they also exhibited antimicrobial activity against oral bacteria.

PMID- 1363466
TI  - Plasma fibrinogen levels and fibrinogen genotype in non-insulin dependent
      diabetics.
AB  - The association between plasma fibrinogen levels, fibrinogen genotype, and the
      development of macrovascular disease was studied in 100 patients with non-insulin
      dependent diabetes mellitus (NIDDM). The mean plasma fibrinogen levels in
      patients with macrovascular disease was higher than those without, although the
      difference was not statistically significant (3.67 g l-1, and 3.43 g l-1,
      respectively). The frequency of the rare allele of the fibrinogen gene DNA
      polymorphism detected with the restriction enzyme Bc1I was slightly higher in the
      group of patients with disease, but the difference was not statistically
      significant (0.20 vs 0.16). The frequency of the TaqI polymorphism rare allele
      was the same in both groups (0.30 vs 0.31). However, the Bc1I polymorphism was
      strongly associated with plasma fibrinogen levels, with those patients
      heterozygous for the rare allele having mean levels 16 per cent higher than those
      lacking the allele (3.81 g l-1 vs 3.28 g l-1, p < 0.05). This data demonstrates
      that variation at the fibrinogen locus is involved in determining fibrinogen
      levels in patients with NIDDM, and suggests the possibility that fibrinogen
      genotype and plasma fibrinogen levels could be one of the factors making a small
      contribution to the development of macrovascular disease in diabetic patients.

PMID- 1363469
TI  - [Bolus tocolysis in theory and practice].

PMID- 1363468
TI  - Hemorrhagic fever with renal syndrome in Yugoslavia: epidemiologic and
      epizootiologic features of a nationwide outbreak in 1989.
AB  - A nationwide epidemic of hemorrhagic fever with renal syndrome (HFRS) occurred in
      Yugoslavia in 1989. Sera from 609 hospitalized patients, from all six Republics
      (Bosnia and Hercegovina, Croatia, Macedonia, Montenegro Serbia, Slovenia) and two
      Provinces (Kosovo and Vojvodina), who had signs and symptoms suggestive of HFRS,
      and sera and lung tissues from 544 small mammals belonging to 13 species were
      studied for evidence of hantavirus infection. Of the 226 patients with
      serologically confirmed HFRS, 182 resided in Bosnia and Hercegovina or in Serbia.
      The severity of disease differed from region to region, with an overall fatality
      of 6.6% (15/226). Patients from southern Yugoslavia tended to have more severe
      disease and exhibited two types of antibody patterns, while approximately equal
      numbers of clinically severe and mild cases of HFRS were registered in central
      Yugoslavia, where four types of antibody patterns were found. Two of these
      antibody patterns suggested the existence of hantaviruses which are antigenically
      distinct from those reported to date. Two seasonal peaks of disease, one during
      the summer and the other in late autumn, were found. Hantaviral antibodies and/or
      antigens were detected most often in the yellow-necked mouse (Apodemus
      flavicollis) (88/189), the wood mouse (Apodemus sylvaticus) (28/146), the striped
      field mouse (Apodemus agrarius) (10/64), the bank vole (Clethrionomys glareolus)
      (36/63), the house mouse (Mus musculus) (14/29), and the Norway rat (Rattus
      norvegicus) (14/21). Five other species of rodents and insectivores were
      infrequently infected.

PMID- 1363467
TI  - Anti-eye muscle antibodies and hypothyroid Graves' disease: a case report.
AB  - We report the case of a 70-year-old man who developed hypothyroidism associated
      with TSH receptor antibodies and severe ophthalmopathy during lithium therapy. He
      had received lithium therapy for more than 20 years for manic depression, when
      ophthalmopathy (class VI of the American Thyroid Association classification) and
      mild hypothyroidism developed. Orbital magnetic resonance imaging indicated
      marked enlargement of the superior, medial and inferior rectus muscles in the
      left eye. He had anti-eye muscle antibodies in his serum, detected by Western
      blotting and quantified by chromatoscanning, as well as anti-TSH receptor
      antibodies. He was treated with supplementation of levothyroxine and four cycles
      of methylprednisolone pulse therapy. After the pulse therapy, both anti-eye
      muscle antibodies and anti-TSH receptor antibodies decreased and disappeared in
      parallel with the improvement in eye symptoms and signs. These observations
      suggest the importance of anti-eye muscle antibodies as clinical markers in the
      development of thyroid-associated ophthalmopathy.

PMID- 1363471
TI  - Abstracts of the 186th Meeting of The Netherlands Ophthalmological Society (NOG)
      Centennial Congress. Maastricht, June 17-19, 1992.

PMID- 1363470
TI  - [A case of prenatal diagnosis of beta-thalassemia by polymerase chain reaction].
AB  - The prenatal diagnosis of beta-thalassemia in the Udin family, where the parents
      were the carriers of 2 bp deletion in the codon 8 (-AA) was undertaken using PCR.
      Five polymorphic restriction endonuclease sites in the beta-globin gene region
      were tested. They are: 2 HindIII sites in the gamma G and gamma A genes, 2 HincII
      sites located in the pseudogene and in its 3'-flanking region, and the AvaIII
      site in the second exon of the beta-globin gene. The heteroduplex analysis was
      also performed. Two HindIII polymorphic sites were informative and the HincII
      site in the pseudogene and the AvaII site in the beta-globin gene were partially
      informative. According to the results of the RFLP analysis, the embryo was
      heterozygous. The similar result was obtained by heteroduplex analysis.

PMID- 1363472
TI  - [AIDS. 3rd European conference on the clinical aspects and treatment of HIV
      infection. Paris, 12-13 March 1992. 4th German AIDS congress. Wiesbaden, 25-28
      March 1992. 8th International AIDS Conference. Amsterdam, 19-24 July 1992].

PMID- 1363473
TI  - [18th World Congress of Dermatology. New York, 12-18 June 1992].

PMID- 1363474
TI  - Activation of CD4+ and CD8+ lymphocyte subsets by streptozotocin in the popliteal
      lymph node assay. II. Comparison with acute graft-vs-host reaction in H-2
      incompatible F1 mouse hybrids.
AB  - Changes in lymphocyte subsets during an acute GVH reaction were compared to STZ
      induced PLN response in mice. The GVH reaction was induced locally by sc
      injection of parental C57Bl/6 [B6] spleen cells into (C57Bl/6 x DBA/2) F1 footpad
      [B6D2F1]. Early cell activation and time-related changes in T- and B-lymphocyte
      subsets were monitored during the onset of the GVH reaction by flow cytometry and
      immunophenotyping. Examination of cell size and chromatin decondensing for T- and
      B-cell subsets showed differences in activation profile during the early phase of
      the GVH reaction. The present study provides direct evidence for early in vivo
      activation of both CD4+ and CD8+ T-cells. Our data confirm the central role of T
      cell activation in the induction of a GVH reaction and suggest that recirculatory
      host B-cells can play an important role in early GVH node enlargement. Overall,
      our comparative analysis supports the concept of polyclonal T-cell activation for
      both STZ-related and GVH-induced lymphoproliferation. Chemicals-induced
      lymphoproliferation leading to autoimmune reactions is a challenging issue. A
      number of drugs and chemicals have been tested in the PLNA assay for
      lymphoproliferative potential. We previously reported the activation and
      proliferation of T-cell subsets following STZ injection into murine footpads. The
      STZ-induced PLN enlargement and proliferation characteristics of T- and B-cell
      subsets were postulated to be similar to those of an acute allogeneic GVHR. In
      the present study, a cytometric analysis of T- and B-cell subsets in PLNs was
      performed during an acute allogeneic GVHR, for comparison purposes. Such a
      reaction results in a massive node enlargement five to ten times that seen after
      stimulation with conventional antigens. Acute GVHR is believed to be a direct
      consequence of the high frequency of alloreactive donor T-cells inducing a
      massive proliferation of B-cells, almost exclusively of host origin, in GVHR
      nodes. It is now widely accepted that donor T-cells activated as the result of
      exposure to foreign MHC antigens in the recipient, secrete various cytokines
      which assist the host B-cells and bypass the normal B-T cell cooperation.
      Induction of an acute GVHR, as in the parental B6--->recipient B6D2F1 model,
      requires the injection of CD4+ and CD8+ donor T-cells into an F1 recipient that
      differs from the parent at both MHC class I and II loci.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1363475
TI  - Ethanol-induced CD3 and CD2 hyporesponsiveness of peripheral blood T lymphocytes.
AB  - The functional relevance of a direct ethanol effect on the membrane structure of
      T lymphocytes and accessory cells (APC), as well as on signal transduction
      systems was studied in ten normal subjects. Ethanol incubation (80 mM for 24h) of
      highly purified T cells increased the number of CD4+/CD45RA+ lymphocytes. In
      contrast, ethanol exposure induced a drop in CD14+/LFA-3+ APC values. These
      changes were accompanied by faulty T-cell proliferation in response to anti-CD3
      and anti-CD2 mAb and inhibition of CD3- and CD2-mediated rises in intracellular
      calcium and, to a lesser extent, inositol 1,4,5-triphosphate levels. These data
      clearly indicate that a membrane-specific ethanol interaction both modifies
      surface glycoproteic and/or glycolipidic structures and alters transmembrane
      transduction of the activation signals.

PMID- 1363476
TI  - Persistent depletion of CD4+ T cells and inversion of the CD4/CD8 T cell ratio
      induced by anti-CD4 therapy.
AB  - A 49-year-old patient with refractory rheumatoid arthritis was treated repeatedly
      with anti-CD4 murine monoclonal antibodies. While the first anti-CD4 treatment
      resulted in a marked, however transient, depletion of CD4+ cells from 1070 to a
      minimum of 175/microliters, a second treatment cycle resulted in a persistent
      decrease. Despite this marked depletion, no major clinical improvement occurred,
      which was in striking contrast to other patients treated in a similar way. Of
      interest, the administration of low doses of chlorambucil led to significant
      clinical benefits. Markedly reduced numbers of CD4+ cells (200-500/microliters)
      were observed for more than 2 years, while the numbers of CD8+ cells increased
      after the second treatment. No infectious episodes occurred. Discontinuation of
      chlorambucil did not lead to increasing amounts of CD4+ cells. In contrast to the
      rapid reduction of CD4+ cells from the blood stream induced by anti-CD4
      infusions, there was a considerable delay until altered CD4/CD8 ratios were
      observed in intraarticular sites. No evidence was found for either humoral or
      cellular immune reactivities towards CD4+ T helper cells. Our findings suggest
      that in certain patients undergoing anti-CD4 therapy there may be a reduced
      capacity of the CD4+ T helper cell pool to regenerate.

PMID- 1363478
TI  - [The surgical operation (a lecture)].

PMID- 1363477
TI  - [Peripheral blood IgA bearing cells in children with Henoch-Schonlein purpura
      nephritis and IgA nephropathy. Relationship between IgA bearing cells and clinico
      pathological findings or T alpha 4 cells].
AB  - It has been reported that patients with Henoch-Schonlein purpura nephritis (HSPN)
      and IgA nephropathy (IgAN) showed an familial increase of IgA bearing peripheral
      blood lymphocyte. To elucidate the relationship between IgA bearing cells and
      clinico-pathological findings or T cell subsets, especially IgA specific helper T
      cells (T alpha 4 cells), 20 patients with HSPN and 33 patients with IgAN were
      studied. The results demonstrated as follows; 1) IgA bearing cells were
      significantly increased in patients with both HSPN and IgAN (p < 0.001). 2) The
      increase of IgA bearing cells was well correlated to the degree of patients'
      proteinuria and hematuria (p < 0.05), and also correlated with the severity of
      patients' renal pathological findings in both diseases. 3) With relation to the T
      cell subsets in patients with both diseases, only the CD4+ Leu8- cells (helper T
      cells) and T alpha 4 cells were significantly increased, in addition, positive
      correlation between IgA bearing cells and CD4+ Leu8- cells or T alpha 4 cells was
      observed. 4) The increase of IgA bearing cells seemed to be transient in HSPN,
      but remained elevated in IgAN. In conclusion, it was indicated that patients with
      HSPN and IgAN could have IgA related immunological abnormalities, which may be
      reflected in the increase of IgA bearing cells and T alpha 4 cells. It was also
      suggested that determination of IgA bearing cells could be a useful parameter
      which may be reflected in the disease activity of HSPN and IgAN.

PMID- 1363480
TI  - [Molecular genetic research into the clinical picture of nerve diseases (gene
      mapping on the chromosomes and DNA-probe diagnosis)].

PMID- 1363479
TI  - [Telethermography in the examination of children following orchiopexy].
AB  - From the results of examination of 60 healthy boys the authors suggest a
      thermographic characteristics of the scrotum in different age groups. It is shown
      with high authenticity that the temperature of the scrotum reduces with age.
      Besides, there is an authentic increase of temperature of the scrotum on the left
      side in children aged from 11 to 14 years. Examination of 317 boys who underwent
      operation for cryptorchidism showed the temperature to be increased by 0.6-0.8
      degree C in the early and by 0.1-0.4 degree C in the late-term postoperative
      period. Distant thermography was found to be highly informative in studying the
      scrotal temperature regimen in healthy children and in those with cryptorchidism
      in the postoperative period.

PMID- 1363481
TI  - [A comparative analysis of the antihypertensive activity of calcium antagonists
      and adrenoblockers in long-term treatment].
AB  - Essential hypertension stage II was treated by calcium antagonists, alpha- and
      beta-adrenoblockers in 362 patients. The drugs were compared for hypotensive
      efficiency at rest and exercise. A significant hypotensive effect was achieved in
      81%, 58%, 44%, 43% and 37% of patients treated with labetalol, nifedipine,
      nadolol, propranolol, diltiazem, respectively. An increase in verapamil daily
      dose from 240 to 600 mg led to a rise in efficacy from 27 to 75% without an
      increase in the number of side effects. The antihypertensive effect of the drugs
      is shown to persist in long-term treatment as shown by exercise tests and static
      loads.

PMID- 1363482
TI  - A simple method for electrical field stimulation of cultured granule cells.
AB  - A method suitable for electrical field stimulation of superfused primary cultures
      of cerebellar granule cells is described. A microchamber of about 0.5 ml was
      obtained by closing the culture dishes with a perspex plug equipped with
      stimulating electrodes and inlet-outlet tubing. Two-minute trains of electrical
      pulses (alternate polarity, 2-ms duration; 100 mA intensity; 10 V drop between
      electrodes; frequency 5, 10 and 20 Hz) applied to cultures kept at 27 degrees C,
      elicited a D-[3H]aspartate outflow which was frequency related, [Ca2+]0
      dependent, tetrodotoxin sensitive. Moreover 2 trains of 10 Hz pulses (S1 and S2)
      at 30-min intervals caused an S2/S1 ratio equal or near to one, thus
      demonstrating that a steady-state condition had been achieved. The NMDA
      antagonist DL-2-amino-5-phosphonopentanoic acid (AP5) but not the non-NMDA
      antagonist, 6-cyano-7-nitroquinozaline-2,3-dione (CNQX), added before S2,
      significantly increased the electrically evoked tritium efflux, suggesting that
      the endogenous transmitter released during electrical stimulation activated an
      NMDA-mediated negative feed-back. This technique of electrical field stimulation
      seems particularly feasible to study the extent and time course of drug effects
      on spontaneous and evoked D-[3H]aspartate outflow.

PMID- 1363484
TI  - Determination of release of endogenous dopamine from superfused substantia nigra
      slices.
AB  - Dopamine (DA) is synthesized and released not only from the terminals of the
      nigrostriatal dopaminergic neuronal pathway but also from cell bodies and
      dendrites in the substantia nigra (SN). In most of the in vitro studies on DA
      release in the SN, release of exogenously applied 3H-DA has been determined
      either from slices or from synaptosomes. However 3H-DA has some disadvantages; 3H
      DA is taken up and released not only from dopaminergic cells but also from other
      neuronal elements and radiolabelled DA may not be evenly distributed with the
      releasable endogenous pool of the amine. Therefore we have developed a method for
      determination of the release of endogenous DA from superfused guinea pig SN
      slices. We have used a superfusion system in which 6 slices are placed into a
      microchamber. Samples of superfusate were collected every 10 min for up to 3 h
      and biochemical analyses were performed by electrochemical detection preceded by
      absorption of DA on alumina and chromatography on a cation exchange column.
      Expected increases of the release of endogenous DA were obtained following D
      amphetamine and potassium administration. The data indicate that it is possible
      to measure endogenous release of DA from guinea pig SN slices with standard HPLC
      technique and follow the release for a relatively long time.

PMID- 1363483
TI  - Fast in vivo monitoring of electrically evoked dopamine release by differential
      pulse amperometry with untreated carbon fibre electrodes.
AB  - Differential pulse amperometry has previously been used in combination with
      electrochemically treated carbon fibre electrodes. In order to improve the time
      resolution, this technique was combined here with untreated electrodes. Dopamine
      release was evoked in the nucleus accumbens of rats anaesthetized with urethane
      by electrical stimulation of the mesolimbic dopaminergic pathway. The
      differential oxidation current appearing at +200 mV was recorded every 1 s and
      was proportional to the dopamine concentration from 0.5 to 50 microM. At this
      voltage these untreated electrodes were not sensitive to the main catechol
      metabolite (DOPAC) and poorly sensitive to ascorbic acid. The electrically evoked
      increase in the oxidation current corresponded exclusively to dopamine. It was
      enhanced by nomifensine, amphetamine, haloperidol and pargyline and reduced by
      alpha-methyl-p-tyrosine (A-MPT). The results show that the evoked DA release was
      facilitated by increasing the stimulation frequency from 10 to 40 Hz. The method
      was sufficiently sensitive to detect dopamine release evoked by electrical
      stimulation at 10 Hz and its time resolution was 1 s.

PMID- 1363485
TI  - A simple biological way to screen dopaminergic agonists.
AB  - The velocity of propagation of the in vitro retinal model of spreading depression
      is very sensitive to changes in the ionic composition of the extracellular medium
      and also to the the addition of different drugs. 10 microM of SKF 38393, a D1
      agonist, increases the velocity of propagation of the wave while 10 microM of
      Quinpirole, a D2 agonist, decreases it. Both changes are blocked by their
      specific antagonists, SCH23390 and 1-sulpiride respectively. This assay can
      biologically screen potential dopaminergic drugs indicating its physiological D1
      and/or D2 preferred effect in the tissue for future analysis by other different
      methodologies.

PMID- 1363486
TI  - Somatostatin and its analogs in the short bowel syndrome.
AB  - The use of somatostatin to manage diarrhea associated with the short gut syndrome
      is impractical because of its need to be given by continuous infusion and a
      rebound effect on stool output with cessation of therapy. Octreotide has been
      used more successfully to control stool and electrolyte losses in patients with
      shortened gastrointestinal tracts. In published series and studies, all subjects
      appear to decrease stool losses, but clinical benefit for long-term use is not
      achieved for all patients. In the patients who do respond, the need for
      parenteral nutrition and intravenous hydration has been decreased or eliminated.
      The optimal dose is unclear, but many patients respond to 50-micrograms
      injections twice daily. Several investigations noted no additional beneficial
      effects with escalating dosages. Adverse effects include impairment of fat
      absorption, which may offset the therapeutic benefits of octreotide. The patients
      with the greatest response appear to have the least fat malabsorption. Other
      adverse effects noted when using octreotide for control of the short gut syndrome
      include pain associated with subcutaneous injection and abdominal complaints.
      Other potential concerns include the effect on gallstone formation in this high
      risk population and intestinal adaptation.

PMID- 1363487
TI  - Symposium on nutrition, women, and their health.

PMID- 1363489
TI  - Management of Acute Pain. Proceedings of a symposium. 1991.

PMID- 1363490
TI  - Differential in vivo and in vitro effect of gentamicin on glutamate synthesis and
      glutamate deamination in rabbit kidney-cortex tubules and mitochondria.
AB  - The effect of gentamicin on both glutamate synthesis and glutamate deamination
      was studied in kidney-cortex mitochondria and tubules isolated from both control
      and gentamicin-treated animals. In kidney-cortex mitochondria which were
      permeabilized in order to make a free access of substrates and antibiotic to the
      glutamate dehydrogenase, gentamicin appeared to be a very potent inhibitor of
      glutamate synthesis, resulting in about 60% decrease of the enzyme activity at 5
      mM concentration. Other aminoglycoside antibiotics decreased the enzymatic
      activity, in the following order: gentamicin > neomycin = tobramycin = kanamycin
      > biodacyna > amikacin > streptomycin. This, in principle, corresponds to their
      known nephrotoxic potential observed in vivo. The inhibitory action of
      antibiotics was abolished by neither ADP nor leucine, allosteric activators of
      glutamate dehydrogenase. Surprisingly, gentamicin did not decrease the rate of
      ammonia formation from glutamate when added to both renal tubules and
      mitochondria isolated from control rabbits. This indicates that the antibiotic
      exerts its inhibitory effect on glutamate dehydrogenase activity in the direction
      of glutamate synthesis only. In contrast, the rate of both glutamate deamination
      and glutamate synthesis was about 40% lower in renal tubules and mitochondria
      isolated from kidney-cortex of animals which were given antibiotics for 10 days.
      In view of these results it seems that (i) the depression of ammoniagenesis in
      gentamicin-treated animals may be due to a decrease of glutamate dehydrogenase
      content and (ii) under conditions in vitro the aminoglycoside inhibits the enzyme
      activity in the direction of glutamate synthesis while it does not affect the
      glutamate deamination.

PMID- 1363488
TI  - [Cardiovascular effects of a combination of vecuronium and low-dose fentanyl in
      atropinized and non-atropinized subjects].
AB  - The cardiovascular effects of the pharmacologic association of low-dose fentanyl
      (2 micrograms/kg) and vecuronium (120 micrograms/kg) have been studied in 38 ASA
      I and II atropinized and non-atropinized patients scheduled for abdominal surgery
      during induction of anaesthesia with thiopentone or propofol. Whatever the
      induction agent used, heart rate was consistently reduced in patients not
      receiving an anticholinergic drug, while it was unchanged in patients treated
      with atropine intravenously. In non-atropinized patients impressively lower
      minimum heart rates were observed during induction of anaesthesia with
      thiopentone. In this last group one patient suffered from a cardiac arrest
      resolved without sequelae. In patients treated with the association between
      vecuronium and low doses of fentanyl a pretreatment with atropine is always
      indicated. Propofol seems to be a better induction agent than thiopentone.

PMID- 1363491
TI  - K-opioid receptor changes in experimental models of cerebral ischaemia and
      atherosclerosis in the rabbit.
AB  - Thromboembolic phenomena and transient ischaemic attacks (TIA) are considered the
      basis of ischaemic pathologies. The aim of the present research is to investigate
      the involvement of k-opioid receptors in cerebral blood flow (CBF) impairment
      which results in experimental stroke or dietary atherosclerosis in rabbits. CBF
      measurement showed a significant decrease in rabbits submitted to embolization
      and/or atherosclerosis. Binding studies showed that massive cerebral ischaemia
      and atherosclerosis produced a significant increase in the number of k-opioid
      receptors (Bmax), without changing (KD) affinity values. In conclusion, the
      results obtained seem to indicate that the increase in k-opioid receptors might
      play a crucial role in a common cerebral biochemical mechanism both in ischaemic
      and atherosclerotic pathologies.

PMID- 1363492
TI  - Unexplained hypertension during induction of a patient with phaeochromocytoma.
AB  - An unexplained hypertensive response during the induction of anaesthesia for
      phaeochromocytoma resection is described. This response was not accompanied by
      elevations in plasma catecholamine levels. It occurred despite heavy
      premedication and followed induction with etomidate, alfentanil, lignocaine,
      vecuronium and magnesium sulphate (MgSO4). A bolus of esmolol (0.5 mg/kg) lowered
      the blood pressure rapidly. Subsequent haemodynamic manipulations were carried
      out by varying the rate of an esmolol infusion. A constant background infusion of
      MgSO4 was maintained throughout the procedure. These produced satisfactory
      haemodynamic control despite marked rises in plasma catecholamine levels.

PMID- 1363493
TI  - Methotrexate increases valproic acid-induced developmental toxicity, in
      particular neural tube defects in mice.
AB  - The hypothesis that valproic acid-induced dysmorphogenesis may be due to an
      interference of this drug with folate metabolic pathways was further investigated
      by a study of a possible interaction of valproic acid (VPA) and the established
      folate antagonist methotrexate (MTX). The dihydrofolate reductase inhibitor MTX
      (1.25 and 2.5 mg/kg, i.p.) was injected 15 min prior to VPA (300 and 400 mg/kg,
      s.c.) in day 8 pregnant NMRI mice. Fetuses were examined for exencephaly,
      resorption, and fetal weight retardation on day 18 of gestation. MTX produced no
      exencephaly or reduction in fetal weight, and the 2.5-mg/kg dose caused 56%
      resorption. Higher doses (5-20 mg/kg) produced embryolethality and fetal weight
      retardation, but no exencephaly. VPA (300 and 400 mg/kg) administration resulted
      in 3.4% and 12.6% exencephaly and 9% and 19% resorptions, respectively.
      Coadministration of MTX with VPA significantly increased VPA-induced resorption
      and exencephaly rates as well as fetal weight retardation. Exencephaly induced by
      VPA 400 mg/kg was increased to 29.5% and 24.1% (P < 0.01 and P < 0.05) when given
      with 1.25 and 2.5 mg/kg MTX, respectively. MTX (2.5 mg/kg i.p.) did not alter
      transplacental VPA (400 mg/kg, s.c.) pharmacokinetics. These results support the
      view that VPA-induced teratogenesis may be mediated by interaction with folate
      metabolism.

PMID- 1363494
TI  - Teratological study of stobadin after single and repeated administration in rats.
AB  - The toxic developmental potential of the anti-arrhythmic drug stobadin was
      assessed after single intravenous or repeated oral doses to pregnant rats.
      Stobadin was studied in the form of dihydrochloride (DH 1011) at doses of 2 and 6
      mg/kg, given in single intravenous injections on days 3, 6, 9, or 12 of
      gestation. Immediately after injection of the 6-mg/kg dose of DH 1011 to pregnant
      rats, saccade abdominal respiration, tremor of hindlimbs, and sedative behaviour
      were observed on each day of medication. No deaths of females occurred in either
      the control or experimental groups. Slight foetal toxicity was manifested by
      significantly decreased foetal weight only after treatment on day 3 of gestation
      at 6 mg/kg and by significantly increased incidence of delayed ossification of
      the parietal and supraoccipital bone also at 6 mg/kg DH 1011 given on day 12 of
      gestation. The effect of repeated oral treatment in the form of dipalmitate salt
      (DP 1031) was studied in doses of 5, 15, and 45 mg/kg from days 2-15 of
      gestation. Oral exposure to 45 mg/kg DP 1031 resulted in significant reduction of
      maternal body weight gain and in embryofoetal toxicity, namely, increased
      preimplantation foetal loss, anomalies of sternebrae, and, after 15 and 45 mg/kg
      DP 1031, significantly decreased foetal weight and smaller litter size. The
      relevance of the two routes of stobadin administration for risk extrapolation is
      discussed.

PMID- 1363495
TI  - Transplacental genotoxicity of triethylenemelamine, benzene, and vinblastine in
      mice.
AB  - Transplacental cytogenetic effects of triethylenemelamine (TEM), benzene, and
      vinblastine on maternal mice and their fetuses have been investigated using
      micronucleus and sister chromatid exchange (SCE) as genetic endpoints. CD-1 mice
      were treated on day 14 and 15 of gestation with TEM (0.125, 0.25, and 0.5 mg/kg),
      benzene (439,878, and 1,318 mg/kg), and vinblastine (0.5, 1, and 2 mg/kg) by
      intraperitoneal injection at 24 hr intervals, and sacrificed 40 hr after the
      first injection. Erythrocytic precursor cells in maternal bone marrow and fetal
      livers (2-4) from each pregnant mouse were used for the micronucleus and/or the
      SCE analyses. Significant dose-related increases in both micronuclei and SCE were
      found in maternal bone marrow and fetal liver following TEM treatment. Benzene at
      the highest dose (1,318 mg/kg) also caused a significant increase in micronuclei
      and SCE in both maternal bone marrow and fetal liver cells. The embryonic
      genotoxic effect of TEM was much higher than that of benzene for both genetic
      endpoints, and the frequency of micronuclei induced by benzene was higher in
      fetal liver than in maternal bone marrow cells. Vinblastine, a spindle poison,
      induced micronuclei but not SCE. Micronuclei induction by vinblastine was 7 fold
      greater in maternal bone marrow than in fetal liver cells. All three chemicals
      were cytotoxic in maternal bone marrow cells, but not in fetal liver cells except
      for TEM, which showed a weak cytotoxicity in fetal liver cells in the
      micronucleus assay. These results indicate that TEM, benzene, and vinblastine are
      transplacental genotoxicants in mice.

PMID- 1363496
TI  - Changes in secondary structure of DNA of rat embryos following treatment with
      diethylnitrosamine and methylazoxymethanol acetate in vivo.
AB  - Diethylnitrosamine (DEN) and methylazoxymethanol acetate (MAM) are not
      transplacental carcinogenic but embryotoxic to Wistar rats when administered by
      i.p. injection on day 12 of gestation. MAM, a weak teratogen to rats during this
      period, induced a dose dependent increase in the number of resorptions to 15% and
      40% of the litters following doses of 15 and 25 mg/kg bw, respectively. Rats
      similarly treated with 70, 150, and 180 mg DEN/kg bw resulted in increases in
      total DNA mass of day 13 embryos by 31%, 45% and 52%, respectively, compared to
      the saline treated controls. Twenty percent reduction in total DNA amount was
      detected following 25 mg MAM/kg bw. Benzoylated DEAE-cellulose (BD-cellulose)
      chromatography fractionates DNA on the basis of secondary structure by stepwise
      elution of double-stranded DNA with 1.0M NaCl solution (SE-DNA) followed by
      elution of DNA containing single-stranded regions with caffeine solution (CE
      DNA). Day 13 embryonic DNA was monitored by in vivo labelling with [methyl-3H]
      thymidine (3H-TdR) on days 6 and 7 of gestation. Significant increases in
      percentages of caffeine-eluted DNA (%CE-DNA) compared to control values were
      detected 24 h after treatment of day 12 embryos with 70, 150, and 180 mg DEN/kg
      bw. Such increases were not observed after MAM. Incorporation of [methyl-14C]
      thymidine (14C-TdR) into embryonic DNA demonstrated the effects of treatment with
      these compounds on DNA synthesis in vivo. When compared to saline controls, DEN
      induced significant increases in 14C-TdR incorporation into embryo DNA, 1 h prior
      to analysis, but the increases were not proportional to the doses administered.
      Similar analysis of MAM treated samples showed no significant changes to %CE-DNA
      values. The relative %CE-DNA is expressed as the ratio of the percentage of
      caffeine-eluted 14C-labelled DNA to %CE-DNA (i.e., %CE-14C-DNA:%CE-3H-DNA). In
      the majority of control embryos the 14C-specific activity of CE-DNA was higher
      than the 14C-specific activity of SE-DNA. No significant change to relative %CE
      DNA values of embryos to those of the controls was observed 24 h after treatment
      of day 12 gestation rats with single doses of DEN and MAM. The results of this
      study support the hypothesis that initiation mechanisms of teratogenesis and
      transplacental carcinogenesis are different. The pertinence of %CE-DNA and
      relative %CE-DNA values to teratogenesis and transplacental carcinogenesis is
      also discussed.

PMID- 1363498
TI  - [Abstracts and papers presented at the meeting Biology of Cell in Culture. St.
      Petersburg, 20-22 October 1992].

PMID- 1363497
TI  - Effects of beta-adrenoceptors blocking eye drops in patients with chronic
      bronchitis.
AB  - Beta-blocker eyedrops used on asthmatic patients are known to enhance asthma
      which is, as chronic bronchitis, an obstructive disease of the lung, and an
      authentic bronchoconstriction is always possible. A single blind parallel trial
      in 3 groups of 10 patients with grade II and III chronic bronchitis, was
      conducted to evaluate the cardiovascular and bronchial tolerance of 3 beta
      blocker eyedrops: timolol, betaxolol and carteolol compared to placebo. The
      following parameters were measured during a 90 minutes period: heart rate,
      systolic and diastolic blood pressure, forced expiratory volume in one second,
      vital capacity. It appeared that only heart rate lowers significantly under the
      influence of the beta-blocker eyedrop, the other parameters did not change and no
      difference was noticed between the three eyedrops. However, comparison of
      individual values showed a significant decrease of forced expiratory volume in
      one second in certain subjects and this, although betaxolol is a beta 1 selective
      beta-blocker. Caution should be taken each time beta-blocker eyedrops are
      prescribed for glaucoma to patients with chronic bronchitis.

PMID- 1363499
TI  - [Autoimmune dysthyroidisms with autosomal recessive transmission: 25 cases].

PMID- 1363500
TI  - A comparison of an enzymatic and a gas-chromatographic method for measuring the
      acetate concentration in the blood plasma of cattle.
AB  - The concentration of acetate in blood plasma was measured by both a gas-liquid
      chromatographic method and an enzymatic method using acetyl-CoA synthetase. When
      acetate was measured enzymatically without previous protein precipitation, the
      apparent concentration was lower than when the concentration measured by either a
      gas-chromatographic method or by the enzymatic method after protein precipitation
      with perchloric acid and neutralization.

PMID- 1363501
TI  - [W-probe for microdialysis method in freely moving rat brain].
AB  - Measurements of neuropeptides, neurotransmitters and amino acids in freely moving
      rat brain were performed by microdialysis method. Recently, despite the different
      methods of measurement for each of those compounds, there have been attempts to
      measure them simultaneously from the same sample of brain dialysate, without
      measuring each compound from different samples. However, more sophisticated
      techniques and highly sensitive devices are required, to manage smaller volume
      samples obtained with this recent method. In our study, we present W-probe
      consisting of two probes with cylindrical dialysis membrane with 3 mm length and
      0.222 mm outer diameter, intending to improve this method of analysis, without
      decreasing the recovery rate and sample volume compared with U-probe and
      permitting a clear analysis of acetylcholine and monoamine metabolites, even with
      the use of eserine. The results demonstrated that sample volume did not decrease
      even with slow perfusion rate (2 microliters/min). Thus, the sampling interval
      could be shorter than the previous microdialysis method, permitting the
      measurement of neurotransmitter releasing variation.

PMID- 1363502
TI  - [Genes for human catecholamine-synthesizing enzymes: the structure, expression,
      and pathology].

PMID- 1363503
TI  - Genetically Engineered Vaccines: Prospects for Oral Disease Prevention.
      Proceedings of a workshop. Bethesda, Maryland, November 6-8, 1991.

PMID- 1363504
TI  - Immunization with fimbrial protein and peptide protects against Porphyromonas
      gingivalis-induced periodontal tissue destruction.
AB  - In these studies we have attempted to show that cell surface structures are
      critical antigens for protection against P. gingivalis-induced periodontal
      destruction. Fimbrillin, and in particular a synthetic 20-amino-acid fimbrillin
      peptide, exerts a protective effect in gnotobiotic rats, thus identifying them as
      potentially useful in the development of a vaccine.

PMID- 1363505
TI  - Effect of BRL-35135 on LTB4-induced guinea pig eosinophil chemotaxis.
AB  - The effect of an atypical beta-adrenoceptor agonist, BRL-35135 on leukotriene B4
      induced-guinea pig eosinophil chemotaxis was studied. BRL-35135 and SC-41930
      (leukotriene B4-antagonist) inhibited the chemotaxis in a concentration-dependent
      manner (IC50 = 9.0 x 10(-6) and 2.6 x 10(-7) M, respectively). However,
      isoproterenol, fenoterol and another atypical beta-agonist, BRL-37344 had no
      effects. The inhibitory effect of BRL-35135 was not affected by (+/-)-propranolol
      (10(-4) M). In contrast, the nonselective beta-adrenoceptor antagonist, (-)
      alprenolol (10(-4) M) dextrally shifted the inhibitory curve of BRL-35135. The
      response to BRL-35135 was antagonized in a competitive manner by (-)-alprenolol,
      with the slope of the Schild plot close to unity, and a pA2 value of 5.62. These
      findings suggest that guinea pig eosinophils possess an "atypical receptor",
      which differs from either beta 1-, beta 2- or atypical beta-adrenoceptor on
      guinea pig ileum, and through which eosinophil chemotaxis can be modulated by BRL
      35135.

PMID- 1363507
TI  - [Medical specialists and meetings: myth of the cave?].

PMID- 1363506
TI  - Differentiation of the U-937 promonocytic cell line induced by phorbol myristate
      acetate or retinoic acid: effect of aurothiomalate.
AB  - Tissue macrophages, which participate in chronic synovial inflammation,
      differentiate from haemopoietic precursors in bone marrow and subsequently in
      tissue. During this process, they acquire attributes which are essential for
      their function in inflammation. Modulation of this process may represent a means
      of regulating inflammatory competence of macrophages in inflammatory joint
      disease. The action of aurothiomalate (ATM), an anti-rheumatic gold compound, on
      the differentiation of a promonocytic cell line (U937) was, therefore, examined
      in in vitro systems. U937 cells exposed to retinoic acid (RA) for 4 days or to
      phorbol myristate acetate (PMA) for 2 days acquired characteristics of
      macrophages, including the capacity to produce superoxide (O2-), responsiveness
      to formyl-methionyl-leucyl-phenylalanine (fMLP) and reduced proliferation. The
      activity of transglutaminase also increased in RA-exposed cultures. The effect of
      ATM exposure on acquisition of these characteristics was small and differed
      between RA- and PMA-stimulated cells.

PMID- 1363509
TI  - Frontiers of Science: Reports from the Final International Session of the Moscow
      Refusnik Seminar.

PMID- 1363508
TI  - Treatment of polyarteritis nodosa and Churg-Strauss syndrome. A meta-analysis of
      3 prospective controlled trials including 182 patients over 12 years.
AB  - To define the most effective treatment for polyarteritis nodosa (PAN) and Churg
      Strauss syndrome (CSS), we undertook 3 consecutive prospective therapeutic trials
      including 182 patients and tried to answer several important questions: should
      cyclophosphamide (CYC) be given as the first-line treatment? what is the place of
      plasma exchanges (PE) in the treatment of systemic vasculitis? does hepatitis B
      virus (HBV)-related PAN require specific treatment? Our first randomized trial in
      71 patients compared the association of CYC with corticosteroids (CS) and PE to
      CS and PE, in order to evaluate the efficacy of CYC given as the first-line
      treatment to control disease activity and subsequent survival of PAN and CSS
      patients. Between December, 1983, and December, 1988, we conducted two trials
      simultaneously: one aimed at patients without HBV markers and the second at
      patients with HBV markers. In 78 patients without HBV markers, we compared
      prednisone and PE to prednisone alone as the initial therapeutic regimen. In 33
      patients with PAN related to HBV, a new therapeutic strategy was applied as an
      alternative to long-term steroid and immunosuppressive therapy: short-term
      steroid therapy and PE were used to control the evolution of PAN and anti-viral
      therapy was administered to suppress the etiological agent of the vasculitis.
      Twelve years after the beginning of the trials on PAN and CSS patients, we think
      that the therapeutic strategy should be as follow: in PAN without HBV and CSS:
      Prednisone in association with CYC improves the control of the disease despite
      infectious side effects which may be reduced by better CYC dose adaptation. It is
      also possible that CYC could be more effective in some subgroups of PAN, for
      instance those with clinical symptoms of poor prognosis. We are presently
      attempting to optimize the CYC prescription (pulses of CYC) in PAN and CSS in the
      hope of improving prognosis; in PAN related to HBV: The first-line treatment
      should be the association of anti-viral agents and PE. This treatment was
      effective and cured a majority of patients within 2 to 3 months; half of them
      seroconverted. The length of HBV infection before its diagnosis, delay before
      initiation of treatment and previous immunosuppressive therapy led to a poor
      seroconversion rate; the role of PE in the treatment of systemic necrotizing
      angiitis: PE are obviously useful in PAN related to HBV where immune complex
      deposition has been demonstrated.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1363510
TI  - Effect of hexafluoro-1,25-dihydroxyvitamin D3 and sodium butyrate combination on
      differentiation and proliferation of HL-60 leukemia cells.
AB  - We have investigated the combined effects of 1,25-dihydroxyvitamin D3 [1,25
      (OH)2D3] and its fluoroanalog 26,26,26,27,27,27-hexafluoro-1,25-(OH)2D3 [F6-1,25
      (OH)2D3] with sodium butyrate (NaB) on growth and differentiation of HL-60 human
      promyelocytic leukemia cells. F6-1,25-(OH)2D3 was 10-fold more active than 1,25
      (OH)2D3 for induction of cell differentiation in HL-60 cells. Exposure to
      suboptimal concentration of F6-1,25-(OH)2D3 and NaB had synergistic effects
      compared to that of F6-1,25-(OH)2D3 or NaB alone and in the presence of 0.1-0.3
      mM NaB, the dosage of F6-1,25-(OH)2D3 required to inhibit cell growth and colony
      formation and to induce cell differentiation was significantly reduced. The
      mechanism for the synergistic effect is probably that NaB increases cytoplasm
      content and nuclear binding of 1,25-(OH)2D3.

PMID- 1363511
TI  - Expression of HER-2/neu oncoprotein in human breast cancer: a comparison of
      immunohistochemical and western blot techniques.
AB  - Three hundred and one primary breast cancers from patients with tumor infiltrated
      lymph nodes were analyzed for the presence of HER-2/neu oncoprotein by two
      procedures: Western blot (WB) and immunohistochemistry (IHC). Overexpression of
      this protein was found by WB in 16.6% of the tumors, and by IHC in 16.3%.
      Concordance between the two methods was found in 95% of tumors (286/301). In 7
      cases we found HER-2/neu by IHC but not by WB, while the opposite was found in
      the remaining 8 patients. This discrepancy was found mainly in samples with HER
      2/neu values just above the cut points and were therefore close to the
      sensitivity limits of the procedures used here. This study helps to define the
      parameters that should be considered to evaluate the immunostaining for HER-2/neu
      as positive (i.e., membrane staining, IHC score of 2 or more). The results
      obtained by both techniques were correlated with several currently used
      prognostic factors. Higher HER-2/neu protein expression was found in tumors
      lacking estrogen or progesterone receptors, in tumors with high S-phase fraction
      and in patients with more than 3 positive lymph nodes. In contrast, no
      relationship was found between overexpression of this protein and tumor size,
      ploidy, or age of the patient. Patients with elevated HER-2/neu expression showed
      a significantly worse overall survival by both methods, IHC (p = 0.05) and WB (p
      = 0.001). In conclusion, there is very high agreement between IHC and WB when
      measuring expression of HER-2/neu and both techniques showed prognostic
      significance.

PMID- 1363512
TI  - Presence of p53 mutation in human cervical carcinomas associated with HPV-33
      infection.
AB  - In this present study, we report the mutation of the p53 gene in vivo in human
      primary carcinomas of cervix and cervical intraepithelial neoplasia (CIN). The
      association of the HPV subtypes with the tumors was determined by multiplex
      primer polymerase chain reaction (PCR) amplification. The mutation of the p53
      gene was detected using PCR amplification of the p53 exons followed by SSCP
      (single strand conformation polymorphism) and DNA sequencing analysis. The p53
      mutation was detected in two out of two HPV-33 positive carcinomas but was absent
      in the HPV-16/-18 positive carcinomas (0 out of 8 cases). The p53 mutation was
      also detected in one out of four HPV-negative cervical carcinomas. No mutation of
      the p53 gene was detected in the CIN specimens (0 out of 7 cases). The two
      mutations in the HPV-33 associated cervical carcinoma were detected at codon 273
      (CGT to TGT; arginine to cysteine) and intron 5 (24 base pair downstream of the
      3' end of exon 5). The p53 mutation at codon 273 has been previously reported in
      one of the HPV-negative cervical carcinoma cell line (C33A). Our results indicate
      that mutation of the p53 gene is not a common event in human cervical cancers
      (3/14), and may be related to the infection of HPV-16/18 in the tumor. However,
      mutation of the p53 gene was detected in cervical carcinomas associated with HPV
      33 and may be an important genetic event in this subgroup of carcinomas.

PMID- 1363513
TI  - Immunoenzymatic assay of erbB2 protein in cancer and non-malignant breast tissue.
      Relationships with clinical and biochemical parameters.
AB  - The erbB2-encoded protein p185 was determined in 130 breast cancer specimens and
      in 29 non-malignant breast tissues using a recently available ELISA method. The
      assay showed good characteristics of precision and accuracy. In the non-malignant
      tissue p185 concentrations were normally distributed and directly correlated with
      estrogen receptors (ER) and progesterone receptors (PR). In cancer tissue p185
      showed higher concentrations than in non-malignant tissue. No relationships were
      found between p185 and the main clinical and pathological parameters, except that
      a direct association with nuclear grade was found. We have categorized the breast
      cancer samples according to p185 concentrations as p185-negative (concentrations
      lower than the higher non-malignant tissue) and p185-positive. Our data suggested
      a different behaviour of p185 in samples with low or high p185 concentrations.
      Indeed, in p185-negative samples the concentrations were directly correlated with
      both ER and PR. Conversely, p185-positive samples were directly associated with
      node status and pT, and inversely associated with ER and PR.

PMID- 1363514
TI  - Increase of vinblastine accumulation by inhibitors of calmodulin-dependent cell
      functions in rat ascites hepatoma AH66 cells.
AB  - ML-9, an inhibitor for myosin light chain kinase, and W-7, a calmodulin
      inhibitor, suppressed the efflux of vinblastine and increased the intracellular
      accumulation of vinblastine, but W-5, an inactive compound for calmodulin, did
      not so in rat ascites hepatoma AH66 cells, which have a multidrug-resistant
      phenotype. In sensitive counterpart AH66F cells, W-7 and ML-9 were less
      effective. W-7 and ML-9 did not interfere with [3H]azidopine photolabeling of P
      glycoprotein in the plasma membrane from AH66 cells. While P-glycoprotein is
      reported to be superphosphorylated by protein kinases, W-7 did not influence the
      phosphorylation of the P-glycoprotein in AH66 cells. There may be an unknown
      Ca(2+)-calmodulin-dependent mechanism in the extrusion of vinblastine from AH66
      cells.

PMID- 1363515
TI  - Lack of reversal of daunorubicin resistance in HL60/AR cells by cyclosporin A.
AB  - Cyclosporin A and verapamil are substrates for P-glycoprotein. Both agents are
      known to reverse multidrug resistance in cells overexpressing P-glycoprotein. In
      this investigation, we have examined the effects of cyclosporin A and verapamil
      on multidrug resistance in HL60/AR cells that lack P-glycoprotein. In addition, a
      correlation was sought between an alteration in plasma membrane potential as
      measured with cationic dye DIOC5 and overexpression of P-glycoprotein. HL60/AR
      cells accumulated 3 fold less daunorubicin than HL60 cells. The drug accumulation
      defect and drug resistance in HL60/AR cells were partially corrected by verapamil
      and buthionine sulfoximine. However, cyclosporin A had no detectable effect on
      daunorubicin accumulation or drug resistance in HL60/AR cells. The multidrug
      resistant P338/ADR cell line overexpressed P-glycoprotein and exhibited
      depolarization of plasma membrane when compared to its corresponding drug
      sensitive parental cell line. In contrast, HL60/AR cells lacked P-glycoprotein
      and plasma membrane potentials were similar to those of drug sensitive HL60
      cells. These results suggest that [1] verapamil modulates daunorubicin transport
      by a mechanism independent of P-glycoprotein, [2] the mechanisms of reversal of
      multidrug resistance by verapamil and cyclosporin A are distinct, and [3] the
      plasma membrane depolarization in multidrug resistant cell lines that overexpress
      P-glycoprotein, as determined by DIOC5, may be due to an increased efflux of
      cationic dye by P-glycoprotein, rather than a true measurement of plasma membrane
      potential in multidrug resistant cells.

PMID- 1363516
TI  - Human lung cancers growing on extracellular matrix: expression of oncogenes and
      growth factors.
AB  - The goal of this study was to evaluate the extracellular matrix (ECM) as a model
      for growing human lung cancers and to study the feasibility of its application
      for cellular and molecular studies of tumor biology. Bovine corneal endothelial
      cell ECM coated dishes were evaluated as a growth substrate for tumor cultures.
      Growth success, morphology and oncoprotein/growth factor expression for 74
      different lung cancers (adenocarcinoma, epidermoid carcinoma and small cell
      carcinoma) were compared after seeding fresh surgical explants onto bovine
      corneal endothelial cell ECM and plastic culture substrate. Nineteen out of 74
      tumors (26%) plated on ECM demonstrated measurable growth. Growth on ECM was
      superior to growth on plastic for the lung tumors. All 19 tumor cultures showed
      malignant morphology and functions. They were examined under the light
      microscope, and in all cases pre- and post-cytology confirmed malignancy. Tumor
      cells seeded on ECM retained their malignant phenotype in comparison to tumors
      grown on plastic. Several oncoproteins (c-myc, c-Ha-ras, c-erbB-2) and growth
      factors/receptors (EGF, EGF-R, TGF alpha) were immunostained. These analyses were
      performed immediately after disaggregation of tumor cells obtained surgically and
      after seeding on ECM or plastic. Strong expression of oncoproteins/growth factors
      was detected in tumor cells immediately after surgery or when the cells were
      plated on ECM. On the other hand, moderate or no expression was observed in the
      same type of cells on plastic.

PMID- 1363519
TI  - Abstracts of the Third International Conference of Anticancer Research. Crete,
      Greece, 21-25 October 1992.

PMID- 1363518
TI  - Expression of c-erbB-2 gene in human head and neck carcinoma.
AB  - The c-erbB-2 oncoprotein is a transmembrane protein the presence of which has
      been associated with poor prognosis in several human neoplasms. However, there
      has been no comprehensive assessment of its value as a potential prognostic
      marker in head and neck squamous cell carcinoma. Archival specimens from 93
      patients, treated surgically for squamous cell carcinoma of the head and neck
      between 1981 and 1989, were analyzed by immunohistochemistry using an anti-c-erbB
      2 monoclonal antibody; of these, 43 (46%) were positive for c-erbB-2 staining.
      The majority of stained specimens (41%) displayed staining predominantly at the
      cell surface, while mixed membrane and cytoplasmic staining was less common (9%).
      Only 4% shared exclusively cytoplasmic staining. Since the specimens were
      archival, the cytoplasmic staining is probably a consequence of variable handling
      and/or fixation at the time of tissue removal. Therefore, only cases exhibiting
      distinct cell surface membrane staining in more than 10% of tumor cells were
      regarded as positive. There is a definite association between immunohistochemical
      detection of c-erbB-2 and head and neck squamous cell carcinoma, since almost
      half of the tumor specimens manifested detectable c-erbB-2 protein. However, this
      association could not be extended to a predicted disease progression or outcome,
      since there was no significant correlation between c-erbB-2 staining and tumor
      size, stage of disease, histologic differentiation, lymph node status or patient
      survival.

PMID- 1363520
TI  - Expression of p53 gene in B-CLL peripheral lymphocytes.
AB  - The p53 tumor suppressor gene expression has been studied in 23 B-CLL cases at
      different clinical stages. The analysis failed to show a direct correlation with
      each stage, but the significantly lower frequency of a BglII RFLP in the
      pathologic population suggests a role of this gene in B-CLL. Northern Blot
      analysis showed the expression of p53 mRNA in all the B-CLL cases. A protocol for
      the RT-PCR methods was set up to study a very small amount of materials which
      should be better used for sequence analysis.

PMID- 1363517
TI  - Expression of protein kinase C in human renal cell carcinoma cells with inherent
      resistance to doxorubicin.
AB  - The expression of protein kinase C (PKC) was analyzed in 18 primary cell cultures
      of human renal cell carcinomas by means of immunocytochemistry. We found that a
      high PKC expression significantly correlates with both resistance to doxorubicin
      and high P-glycoprotein expression. These data support the hypothesis that PKC is
      involved in inherent drug-resistance by phosphorylation and regulation of P
      glycoprotein.

PMID- 1363522
TI  - Nerve-dependent expression of c-myc protein during forelimb regeneration of
      Xenopus laevis froglets.
AB  - The consequences of denervation on the expression of c-myc protein have been
      analyzed on the regenerating forelimb of young froglets of Xenopus laevis. The
      level of c-myc expression, low in control limbs and enhanced in the regenerate,
      is transiently increased after a three-hour total denervation. For this protein,
      the level of expression is not a function of the quantity of nerve in the
      regenerate. Four days after denervation, c-myc signal is back to its base level
      observed in the regenerate. A different pattern of expression is obtained for an
      S phase marker (PCNA protein) taken as a control in the same experimental
      conditions. The data presented here show that the nervous system normally exerts
      a negative control on the expression of c-myc and PCNA proteins in the limb
      regenerate of Xenopus.

PMID- 1363521
TI  - Molecular cloning and characterization of gravity specific cDNA in rice (Oryza
      sativa L.) suspension callus.
AB  - Rice (Oryza sativa L. var. Nipponbare) suspension callus was exposed to gravity
      stress at 450,000 g for 2 hours, after which poly(A)+RNA was isolated and a cDNA
      library was constructed. Three different gravity specific cDNAs, namely, GSC 128,
      GSC 233 and GSC 381 of 0.67, 0.60 and 0.68 kilobase pairs and transcripts of 1.9,
      1.6 and 2.0 kb, respectively, were isolated by differential screening and
      Northern hybridization. The maximum level of transcript was achieved after 4
      hours of exposure to gravity at 450,000 g for GSC 128, 2 hours for GSC 233 and 8
      hours for GSC 381 followed by a gradual decrease to undetectable levels with the
      extension of gravitation time. Callus (GSC 128), shoot and callus (GSC 381) and
      root and callus (GSC 233) specific expression of transcripts was identified.
      Although the protection of callus by treatment with ABA, kinetin and sucrose
      extended the period of expression of mRNA in suspension callus after gravity
      exposure, the expression of gravity-inducible mRNA was exclusively regulated by
      the degree of callus viability or survival after the stress. In addition, we
      demonstrated that the level of GSC 381 transcript was markedly increased by
      exposing the cell to periodical gravity stress, suggesting that this mRNA is
      expressed and translated into special proteins which are closely related to the
      survival of the cell against gravity stress. The sequence of GSC 233 and GSC 381,
      consisting of 417 and 531 base pairs of the longest open reading frames, encode
      polypeptides with calculated molecular weights of 15.29 and 19.47 kDa,
      respectively. A sequence homology search against a data bank revealed that GSC
      233 and GSC 381 differed from other stress inducible genes in terms of the coding
      sequence and expression characteristics.

PMID- 1363523
TI  - Differential expression of the mouse and human Thy-1 gene in embryonal carcinoma
      cells.
AB  - Mouse P19 embryonal carcinoma (EC) cells express on their surfaces a Thy-1
      glycoprotein. The expression of Thy-1 at the mRNA and protein levels is down
      regulated during differentiation induced by retinoic acid (RA). Thy-1 is also
      expressed in human NTERA-2 EC cells, but its expression is not down-regulated
      during RA-induced differentiation. As a first step towards understanding
      differential regulation of the mouse and human Thy-1 gene in EC cells, we have
      introduced genomic DNA fragments encompassing the mouse or human Thy-1 gene into
      NTERA-2 and P19-derived cells and analyzed surface properties of the
      transfectants. In the transient transfection assay, both mouse and human Thy-1
      genes were expressed on cell surfaces at comparable levels. P19-derived stable
      transfectants exhibited great clonal variations in the expressions of the
      transfected Thy-1 gene products, which in part reflected copy numbers. There was
      no simple correlation between the expression of the transfected Thy-1 gene and
      two stem cell surface markers, TEC-1 and TEC-4. In the course of differentiation
      induced by RA several clones with a surface phenotype of EC cells exhibited a
      significant decrease in the expression of the transfected mouse Thy-1, whereas
      expression of the human Thy-1 was less efficiently down-regulated. The results
      suggest the presence of multiple cis- and trans-acting elements controlling
      expression of the mouse and human Thy-1 genes in P19 EC cells and their
      differentiated derivatives.

PMID- 1363524
TI  - [A preliminary study of immuno-electron microscopy of endothelium in
      cardiovascular system].
AB  - The immunocytochemical localizations of the von Willebrand factor (vWF),
      endothelin-1 (ET-1) and the beta 2-adrenergic receptor (beta 2R) in cultured
      human umbilical vein endothelial cells (HUVEC) after thrombin treatment have been
      demonstrated. Competitive ELISA analysis of these treated cells indicate an
      increase in vWF deposition on the subendothelial matrix (1.5 folds vs control)
      and vWF release (3.8 folds vs control) in the culture medium. The vWF-peroxidase,
      immunogold labeling and in situ hybridization of ET-1 were demonstrated on HUVEC.
      Double labelling with different sized gold particles for the ET-1 and beta 2R
      locations were performed on the hearts of young adult WEY, SHR, and SHRsp rats.
      The results were as follows. (1) Positive vWF deposits were detected on the
      extracellular matrix, Weibel-Palade bodies and secreting vesicles in the
      cytoplasm. It is suggested that both the constituted and regulated pathways are
      involved in the secretion of vWF stimulated by thrombin. (2) The gene expression
      of ET-1 was detected by light microscopic in situ hybridization in HUVEC. (3) ET
      1 was detected by immunoelectron microscopy in the lysosome, cell surface, and
      extracellular matrix, suggesting that lysosome possibly plays an important role
      in the processing of ET-1 in HUVEC. (4) The presence of both ET-1 and beta 2R
      have been successfully detected in adult heart tissues and the endothelial cells
      of rats. These observations suggest the functional importance of ET-1 and beta
      2R.

PMID- 1363525
TI  - [Using 131I-MIBG and 99mTc-MDP bone scan for localization of rare extra-adrenal
      pheochromocytomas: report of 2 cases].
AB  - It is difficult, but important, to diagnose extra-adrenal pheochromocytomas
      before surgery. Failure to recognize the existence and nature of an extra-adrenal
      pheochromocytoma can cause life-threatening problems even in a minor surgical
      operation. We present two rare cases of extra-adrenal pheochromocytomas which
      were detected by 131I-MIBG scintigraphy. One of them was intrapericardial, and
      the other was a vesical pheochromocytoma. We used a combined 99mTc-MDP bone scan
      and 131I-MIBG scintigraphy to locate the pheochromocytomas. Both cases of extra
      adrenal pheochromocytoma were correctly diagnosed preoperatively and successfully
      resected in the subsequent operations.

PMID- 1363527
TI  - The physiology, pharmacology, and biophysics of ganglionic transmission. Symposia
      of the International Brain Research Organization. Edmonton, Alberta, Canada,
      August 12-14, 1991.

PMID- 1363526
TI  - [Blood pressure and metabolic response to converting enzyme inhibitor in
      hypertensive patients: comparison between delapril and captopril].
AB  - The antihypertensive and metabolic responses to delapril and captopril in
      hypertensive patients were studied. Forty-six hypertensive patients entered the
      study and were divided into two groups. The delapril group included 21 essential
      hypertensive and five renoparenchymal hypertensive patients; while the captopril
      group included 11 essential hypertensive and nine renoparenchymal hypertensive
      patients. The patients in the delapril group took delapril 7.5 mg twice a day for
      2 weeks. If the antihypertensive effect was inadequate, the dose was increased to
      15mg twice a day, and then to 30mg twice a day. The period of delapril treatment
      was 12 weeks. The patients in the captopril group took captopril 25 mg twice a
      day or three times a day for 12 weeks. After delapril treatment, there were
      significant decreases in the systolic (from 163 +/- 17 to 141 +/- 15 mmHg) and
      diastolic blood pressure (from 105 +/- 13 to 91 +/- 10 mmHg). There were also
      significant decreases in the systolic (from 161 +/- 18 to 141 +/- 24 mmHg) and
      diastolic blood pressure (from 100 +/- 10 to 90 +/- 12 mmHg) after captopril
      treatment (p < 0.001). The pulse rates in both groups showed no significant
      changes after treatment. The laboratory data in both groups showed few changes
      after treatment. Plasma renin activity increased after delapril treatment. A
      cough was the side effect most commonly seen. We conclude that hypertensive
      patients have the same blood pressure and metabolic responses to delapril as
      captopril.

PMID- 1363528
TI  - Energy metabolism and effects of energy depletion or exposure to glutamate.
AB  - The entire program of the first day of the IBRO satellite meeting entitled Ions,
      Water, and Energy in Brain Cells was devoted to the subject of energy. There were
      three sessions on the topics of energy metabolism, activation, and development
      and pathological conditions, followed by a final general discussion on the
      contents of the day's topics. During this general discussion there were spirited
      exchanges on the role of glycogen in the energy metabolism of the brain, on the
      metabolic source of the energy consumed by functional activity, e.g., glycolytic
      or oxidative energy metabolism, and on the sources of the acid-equivalents that
      are responsible for the tissue acidosis accompanying cerebral hypoxia. Despite
      the arguments pro and con presented on all of the issues that were discussed, it
      is doubtful that a consensus was achieved on most of the issues.

PMID- 1363529
TI  - Ca2+ and filopodial responses to glutamate in cultured astrocytes and neurons.
AB  - Neurons and glia exhibit complex homeostatic interactions via shared
      extracellular space which can involve metabolites, inorganic ions, and
      neurotransmitters. Focal application of glutamate to both human and rat central
      nervous system astrocytes in primary culture produced a rapid, transient increase
      in both cytoplasmic and nuclear Ca2+. These Ca2+ waves can propagate at up to 15
      20 micron/s for long distances (millimetres) through the astrocyte syncitium.
      Oscillatory Ca2+ signals were frequently observed under control conditions and
      were enhanced by glutamate application. These Ca2+ signals were paralleled by
      rapid extensions of filopodia from the astrocyte cell margin and apical surface
      near the point of glutamate application. Focal application of glutamate to rat
      hippocampal neurons also elicited rapid, transient increases in intracellular
      Ca2+. Levels of Ca2+ signals were consistently two- to three-fold greater in
      pyramidal neurons cultured from CA1 than in those from CA3. Filopodial extension
      was extensive in CA1 neurons, but rare in CA3 neurons, and in either case
      observable only during the first few days of primary culture. Diversity of glial
      and neuronal responses to binding the glutamate receptors may reflect their roles
      in homeostatic interactions.

PMID- 1363530
TI  - The regulation of pH in the central nervous system.
AB  - The pHi regulation from intracellular acidosis in the central nervous system
      appears to be mediated by mechanisms driven by the large inwardly directed Na+
      gradient. The involvement of these mechanisms in pHi regulation of neurones and
      glial cells has been investigated in the leech central nervous system using ion
      selective microelectrodes. For recovery from acidification, there appear to be
      three separate mechanisms: Na+/H+ exchange, Na(+)-dependent Cl-/HCO3- exchange,
      and Na+-HCO3- cotransport. All three mechanisms have a profound effect on the
      maintenance of pHi homeostasis in glial cells; whereas in leech neurones, as in
      other neuronal cells studied previously, the predominant mechanisms are Na+/H+
      and Na(+)-dependent Cl-/HCO3- exchange. In addition to acid extrusion mechanisms
      we also found evidence for Na(+)-independent Cl-/HCO3- exchange. At alkaline pHi
      this exchanger may mediate some of the pHi recovery from intracellular
      alkalinization.

PMID- 1363531
TI  - Alkaline extracellular pH shifts generated by two transmitter-dependent
      mechanisms.
AB  - Recent studies of the effect of gamma-aminobutyric acid (GABA) on brain
      extracellular pH are reviewed. Experiments were performed on isolated turtle
      cerebellum, using double-barrelled pH-sensitive microelectrodes. Superfusion of
      GABA (1 mM) caused a rapid extracellular alkaline shift accompanied by a rise in
      extracellular K+. Washout of GABA was often associated with an acid rebound,
      concomitant with an undershoot of extracellular K+. The GABA-evoked alkaline
      shift was blocked by picrotoxin and mimicked by the GABA-A agonists isoguvacine
      and muscimol. The response persisted in the nominal absence of extracellular
      calcium, but it was reversibly abolished in nominally bicarbonate free media. In
      contrast, extracellular alkaline shifts evoked by repetitive stimulation of the
      parallel fibers were amplified in bicarbonate-free media and were insensitive to
      picrotoxin. These results indicate the existence of separate, transmitter
      dependent mechanisms of extracellular alkalinization: (i) a GABA-A receptor
      mediated process, most likely associated with efflux of bicarbonate ions across
      GABA-A anion channels and (ii) a bicarbonate-independent process associated with
      excitatory synaptic transmission.

PMID- 1363532
TI  - Mechanisms of glial swelling induced by glutamate.
AB  - The mechanisms of glutamate-induced glial swelling have been studied using an in
      vitro model that permits detection of cell volume changes with high accuracy. The
      model allows for a close control of the extracellular environment to study in
      isolation the effect of defined extracellular alterations occurring in brain
      under pathophysiologic conditions. Glutamate was applied in concentrations
      between 50 microM and 10 mM to either C6 glioma cells or astrocytes from primary
      culture. Glutamate uptake was assessed by HPLC measurements of amino acids in the
      extracellular medium. Glutamate at all concentrations tested caused glial
      swelling, which, however, was moderate, with maximal average volume increases
      between 5.0 +/- 1.92 and 18.38 +/- 1.6% of control at 50 microM and 5 mM
      glutamate, respectively. Swelling was concentration dependent and correlated with
      glutamate uptake. After removal of all extracellular glutamate by glial uptake,
      cell volume spontaneously normalized. Pretreatment of the cells for 90 min with
      ouabain (1 mM) to abolish the extracellular/intracellular Na+ gradient, prevented
      glutamate-induced swelling. It is concluded that while glial cells readily
      accumulate glutamate from the extracellular environment to protect neurons from
      excitotoxic effects, swelling results from the increase of intracellular osmotic
      activity due to the uptake of Na+ and glutamate.

PMID- 1363533
TI  - Use of cell cultures to differentiate among effects of various ischemia factors
      on astrocytic cell volume.
AB  - Mouse astrocytes were subjected to in vitro models of ischemia (hypoxia with or
      without substrate deprivation, excess potassium, or elevated glutamate). Three
      hours of hypoxia alone or with substrate deprivation had little effect upon the
      morphology of astrocytes but did cause disaggregation of polyribosomes. Excess
      (12-50 mM) potassium added (as KCl) to a normal isotonic medium also caused no
      swelling; it did, however, cause a shrinkage of cell volume. When 50 mM potassium
      was substituted for a similar amount of sodium, marked swelling occurred.
      Swelling of astrocytes was also seen after addition of glutamate (50 microM to 1
      mM) to the culture medium. These results show that ischemia per se does not
      result in astrocytic swelling; rather, microenvironmental alterations such as
      rising glutamate levels and changes in the sodium/potassium ratios result in
      astrocytic swelling. We conclude that one can use astrocytes in culture to
      dissect out the mechanisms that cause postischemic alterations in astrocytes in
      vivo.

PMID- 1363534
TI  - Foods and chronic urticaria.

PMID- 1363535
TI  - Drug therapy for chronic urticaria.
AB  - Given the variability of patient problems, it is difficult to construct a single
      drug therapy regimen for treatment of chronic urticaria. However, the following
      regimen should prove to be a useful outline to follow for most cases. The first
      line of therapy will usually be antihistamines. In general, antihistamines should
      be always used on a regular basis and not only after hives occur. If drowsiness
      or anticholinergic adverse symptoms limit the use of one drug in effective doses,
      other H1-blockers should be tried. For day-time use, the newer, less sedating
      antihistamines are preferred. If antihistamines fail to control symptoms when
      used at full doses, addition of glucocorticosteroids can be tried for short
      periods. Most patients respond to doses equivalent to 40 mg of prednisone daily.
      The end point of use of corticosteroids is to reach quickly an effective low,
      alternate-day dose followed by their discontinuation.

PMID- 1363536
TI  - Successful management of chronic urticaria.

PMID- 1363537
TI  - Effect of calcium concentration on survival, proliferation and activities of
      alkaline phosphatase, 5'-nucleotidase, gamma-glutamyltransferase and lactate
      dehydrogenase of adult rat hepatocytes cultured in serum-free medium.
AB  - Mature rat hepatocytes were cultured on collagen coated dishes in serum-free
      alpha-modified Eagle's minimum essential medium containing 0.1 microM insulin,
      0.1 microM dexamethasone, 10 mM pyruvate and Ca2+ at concentrations of 0-2 mM.
      Survival of nondivided cells was best in medium containing 2 mM Ca2+.
      Proliferation during 5-day culture was greatest with 0.4 mM Ca2+, but DNA
      synthesis was scarcely affected by the concentration of Ca2+. Both the activities
      of alkaline phosphatase, 5'-nucleotidase, gamma-glutamyltransferase and lactate
      dehydrogenase and the number of cell nuclei of cultures in 0.1 mM and 2 mM Ca2+
      media were assayed over a 5-day period, and their activities were calculated as
      enzyme activities per unit number of cell nuclei. Alkaline phosphatase activity
      increased rapidly during the first day of culture in both media, and its activity
      in 0.1 mM medium was higher than that in 2 mM medium after culture for 3 days.
      The activity of 5'-nucleotidase became higher in 0.1 mM medium than in 2 mM
      medium from day 2 and was maximal on day 3 in both media. gamma
      Glutamyltransferase activity increased and lactate dehydrogenase activity
      decreased with time in culture, both activities showing no appreciable difference
      in the two media.

PMID- 1363538
TI  - The influence of vasodilating beta-blockers on cardiac function and vascular
      resistance in essential hypertension.
AB  - In nearly all forms of established hypertension, the cardinal hemodynamic
      disturbance is an increased total peripheral resistance, while cardiac output is
      abnormally low, particularly during exercise. When left untreated, total
      peripheral resistance increases, cardiac output falls, and blood pressure
      increases over time. The coronary reserve is reduced, and renal as well as
      cerebral resistance increases and blood flow falls. Antihypertensive agents
      effect central hemodynamics differently. Ordinary beta-blockers do usually not
      reduce total peripheral resistance much below pretreatment level, and cardiac
      output is chronically depressed, particularly during exercise. However, the beta
      blockers greatly reduce the workload on the heart by decreasing the heart rate
      pressure product. Modern beta-blockers with vasodilating activity--like
      carvedilol--are based on a combination of beta-blockade and vasodilatation. Such
      beta-blockers also induce a marked decrease in the pressure-heart rate product,
      and some reduction in total peripheral resistance. They cause less depression of
      exercise cardiac output than ordinary beta-blockers. Blood flow to the kidneys
      and the brain is maintained. From a theoretical point of view, this type of
      antihypertensive treatment should maintain good blood pressure control, reduce
      cardiac workload and be associated with less side-effects than ordinary beta
      blockers.

PMID- 1363539
TI  - Coordinate embryonic expression of three zebrafish engrailed genes.
AB  - We have identified three genes, expressed in zebrafish embryos, that are members
      of the engrailed gene family. On the basis of sequence comparisons and analyses
      of their expression patterns, we suggest that two of these genes, eng2 and eng3,
      are closely related to the En-2 gene of other vertebrates. The third gene, eng1,
      is probably the zebrafish homolog of En-1. Subsets of cells at the developing
      junction between the midbrain and hindbrain express three different combinations
      of these genes, revealing a previously unknown complexity of this region of the
      CNS. Other cells, for example, jaw and myotomal muscle precursors, express two of
      the three genes in combinations which, in the myotomal muscles, change during
      development. Cells in the developing hindbrain and fins express only a single
      engrailed gene. We propose that the fates and patterning of these cells may be
      regulated by the coordinate expression of particular combinations of these
      closely related homeoproteins.

PMID- 1363540
TI  - Autocatalysis and phenotypic expression of Drosophila homeotic gene Deformed: its
      dependence on polarity and homeotic gene function.
AB  - Previously published experiments have shown that the endogenous Dfd gene can be
      ectopically activated by its own (heat-shock-driven) product in a subset of cells
      of different segments. This results in the differentiation of maxillary
      structures like cirri and mouth hooks in places where they normally do not
      appear, and represents a phenomenon of autocatalysis of homeotic gene function
      that differs from the normal activation process. We show that this out-of-context
      activation occurs in cells belonging to the anterior compartments of the three
      thoracic and the A1 to A8 abdominal segments and that it requires the normal
      function of the polarity genes wingless (wg) and engrailed (en). The wg product,
      in addition to that of Dfd, appears to be sufficient to activate the endogenous
      Dfd gene in many embryonic cells. We have studied the effect of several homeotic
      genes on Dfd activation and phenotypic expression: Scr, Antp, Ubx and Abd-B
      repress Dfd both transcriptionally and at the phenotypic level, if their products
      are in sufficient amounts. The endogenous abd-A gene does not have a noticeable
      effect, but when it is replaced by an hsp70-abd-A gene, which produces a high and
      uniform level of expression, the phenotypic expression of Dfd is suppressed. Our
      results also suggest that the differentiation of cirri is induced by Dfd
      expressing cells in non-expressing neighboring cells, and that this interaction
      occurs across the parasegmental border.

PMID- 1363541
TI  - Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially
      expressed during early mesodermal patterning in mouse embryos.
AB  - We have isolated two mouse genes, Mox-1 and Mox-2 that, by sequence, genomic
      structure and expression pattern, define a novel homeobox gene family probably
      involved in mesodermal regionalization and somitic differentiation. Mox-1 is
      genetically linked to the keratin and Hox-2 genes of chromosome 11, while Mox-2
      maps to chromosome 12. At primitive streak stages (approximately 7.0 days post
      coitum), Mox-1 is expressed in mesoderm lying posterior of the future primordial
      head and heart. It is not expressed in neural tissue, ectoderm, or endoderm. Mox
      1 expression may therefore define an extensive 'posterior' domain of embryonic
      mesoderm before, or at the earliest stages of, patterning of the mesoderm and
      neuroectoderm by the Hox cluster genes. Between 7.5 and 9.5 days post coitum, Mox
      1 is expressed in presomitic mesoderm, epithelial and differentiating somites
      (dermatome, myotome and sclerotome) and in lateral plate mesoderm. In the body of
      midgestation embryos, Mox-1 signal is restricted to loose undifferentiated
      mesenchyme. Mox-1 signal is also prominent over the mesenchyme of the heart
      cushions and truncus arteriosus, which arises from epithelial-mesenchymal
      transformation and over a limited number of craniofacial foci of neural crest
      derived mesenchyme that are associated with muscle attachment sites. The
      expression profile of Mox-2 is similar to, but different from, that of Mox-1. For
      example, Mox-2 is apparently not expressed before somites form, is then expressed
      over the entire epithelial somite, but during somitic differentiation, Mox-2
      signal rapidly becomes restricted to sclerotomal derivatives. The expression
      patterns of these genes suggest regulatory roles for Mox-1 and Mox-2 in the
      initial anterior-posterior regionalization of vertebrate embryonic mesoderm and,
      in addition, in somite specification and differentiation.

PMID- 1363542
TI  - Connectin, a target of homeotic gene control in Drosophila.
AB  - The homeotic genes of Drosophila encode transcription factors that specify
      morphological differences between segments. To identify the genes that they
      control, we developed a chromatin immunopurification approach designed to isolate
      in vivo binding sites for the products of the homeotic gene Ultrabithorax. Here,
      we report the analysis of one immunopurified binding site. This 110 bp fragment
      maps within a regulatory region of a gene under homeotic control, connectin. A 4
      kb DNA fragment, including the immunopurified binding site, is sufficient to
      reproduce the appropriate homeotic control within a subset of the full tissue
      distribution of connectin. Analysis of the role of the 110 bp binding site
      indicates that it mediates transcriptional controls by Ultrabithorax and other
      homeotic genes. This is the first report of a functional in vivo binding site
      isolated using the chromatin immunopurification method. We also show that the
      protein product of the connectin gene is predicted to be a cell-surface molecule
      containing leucine-rich repeats. The protein, connectin, can mediate cell-cell
      adhesion thus suggesting a direct link between homeotic gene function and
      processes of cell-cell recognition.

PMID- 1363543
TI  - The 412 retrotransposon and the development of gonadal mesoderm in Drosophila.
AB  - We have shown that the expression of the 412 retrotransposon provides a useful
      early marker for the development of the gonadal mesoderm in Drosophila embryos.
      412 is initially expressed in a set of parasegmentally repeated stripes from
      parasegments (PS) 2-14 in the mesoderm at the extended germ band stage. During
      germ band retraction the bulk of 412 expression declines except in dorsolateral
      clusters of cells in PS10, 11 and 12, where high levels of 412 expression remain.
      These mesodermal cell clusters are associated with germ cells and subsequently
      they coalesce, rounding up to form the gonads. The gonadal mesoderm thus appears
      to originate specifically from three abdominal parasegments, PS10, 11 and 12. We
      show that the maintenance of high levels of 412 expression in gonadal mesoderm is
      not induced by contact with germ cells, but rather depends on genetic control by
      the homeotic genes abdominal-A and Abdominal-B.

PMID- 1363544
TI  - Ectopic expression of UBX and ABD-B proteins during Drosophila embryogenesis:
      competition, not a functional hierarchy, explains phenotypic suppression.
AB  - The Abdominal-B (Abd-B) gene, a member of the bithorax complex (BX-C), specifies
      the identities of parasegments (PS) 10-14 in Drosophila. Abd-B codes for two
      structurally related homeodomain proteins, ABD-B m and ABD-B r, that are
      expressed in PS10-13 and PS14-15, respectively. Although ABD-B m and r proteins
      have distinct developmental functions, ectopic expression of either protein
      during embryogenesis induces the development of filzkorper and associated
      spiracular hairs, structures normally located in PS13, at ectopic sites in the
      larval thorax and abdomen. These results suggest that other parasegmental
      differences contribute to the phenotype specified by ABD-B r activity in PS14.
      Both ABD-B m and r repress the expression of other homeotic genes, such as Ubx
      and abd-A, in PS10-14. However, the importance of these and other cross
      regulatory interactions among homeotic genes has been questioned. Since ectopic
      UBX protein apparently failed to transform abdominal segments, Gonzalez-Reyes et
      al. (Gonzalez-Reyes, A., Urquia, N., Gehring, W.J., Struhl, G. and Morata, G.
      (1990). Nature 344, 78-80) proposed a functional hierarchy in which ABD-A and ABD
      B activities override UBX activity. We tested this model by expressing UBX and
      ABD-B m proteins ectopically in wild-type and BX-C-deficient embryos. Ectopic ABD
      B m does not prevent transformations induced by ectopic UBX. Instead, ectopic UBX
      and ABD-B m proteins compete for the specification of segmental identities in a
      dose-dependent fashion. Our results support a quantitative competition among the
      homeotic proteins rather than the existence of a strict functional hierarchy.
      Therefore, we suggest that cross-regulatory interactions are not irrelevant but
      are important for repressing the expression of competing homeotic proteins. To
      explain the apparent failure of ectopic UBX to transform the abdominal segments,
      we expressed UBX at different times during embryonic development. Our results
      show that ectopic UBX affects abdominal cuticular identities if expressed during
      early stages of embryogenesis. In later embryonic stages, abdominal segments
      become resistant to transformation by ectopic UBX while thoracic segments remain
      susceptible. Head segments also show a similar stage-dependent susceptibility to
      transformation by ectopic UBX in early embryogenesis but become resistant in
      later stages. These results suggest that abdominal and head identities are
      determined earlier than are thoracic identities.

PMID- 1363546
TI  - 2nd International Symposium on Anaerobic Bacteria and Infections. Proceedings.
      Vienna, Austria.

PMID- 1363547
TI  - [Response of patients with porphyria cutanea tarda to treatment with a regimen of
      delagil-riboxin].

PMID- 1363548
TI  - [Features of porphyria cutanea tarda observed in Madrid].

PMID- 1363545
TI  - Virulence factors in anaerobic bacteria.
AB  - Various surface structures can be expressed in Bacteroides fragilis, but little
      is known about capsular structures in other non-spore-forming anaerobes. Fimbriae
      have been isolated from Bacteroides fragilis and Porphyromonas gingivalis. The
      importance of iron-repressible outer membrane proteins as virulence factors in
      Bacteroides fragilis is under study. The low endotoxic activity of Bacteroides
      fragilis lipopolysaccharide can be attributed to the chemical composition of this
      organism's lipid A. A tissue culture system for the demonstration of Bacteroides
      fragilis enterotoxin has recently been described. The toxins A and B of
      Clostridium difficile are immunologically distinct. The importance of IgA
      proteases and other enzymes as virulence factors in anaerobic bacteria remains
      unclear.

PMID- 1363550
TI  - Overweight and Dexfenfluramine: A Perspective for the 1990s. Proceedings of a
      symposium of the 3rd European Congress on Obesity. Nice, 1991.

PMID- 1363549
TI  - The 3rd hGH Symposium. Sorrento, May 14-17, 1992.

PMID- 1363551
TI  - Inactivation of Bacillus subtilis glutamine synthetase by metal-catalyzed
      oxidation.
AB  - Instability of Bacillus subtilis glutamine synthetase in crude extracts was
      attributed to site-specific oxidation by a mixed-function oxidation, and not to
      limited proteolysis by intracellular serine proteases (ISP). The crude extract
      from B. subtilis KN2, which is deficient in three intracellular proteases,
      inactivated glutamine synthetase similarly to the wild-type strain extract. To
      understand the structural basis of the functional change, oxidative modification
      of B. subtilis glutamine synthetase was studied utilizing a model system
      consisting of ascorbate, oxygen, and iron salts. The inactivation reaction
      appeared to be first order with respect to the concentration of unmodified
      enzyme. The loss of catalytic activity was proportional to the weakening of
      subunit interactions. B. subtilis glutamine synthetase was protected from
      oxidative modification by either 5 mM Mn2+ or 5 mM Mn2+ plus 5 mM ATP, but not by
      Mg2+. The CD-spectra and electron microscopic data showed that oxidative
      modification induced relatively subtle changes in the dodecameric enzyme
      molecules, but did not denature the protein. These limited changes are consistent
      with a site-specific free radical mechanism occurring at the metal binding site
      of the enzyme. Analytical data of the inactivated enzyme showed that loss of
      catalytic activity occurred faster than the appearance of carbonyl groups in
      amino acid side chains of the protein. In B. subtilis glutamine synthetase, the
      catalytic activity was highly sensitive to minute deviations of conformation in
      the dodecameric molecules and these subtle changes in the molecules could be
      regarded as markers for susceptibility to proteolysis.

PMID- 1363552
TI  - Physiological roles of acetoacetyl-CoA thiolase in n-alkane-utilizable yeast,
      Candida tropicalis: possible contribution to alkane degradation and sterol
      biosynthesis.
AB  - The presence of two types of thiolases, acetoacetyl-CoA thiolase and 3-ketoacyl
      CoA thiolase, was demonstrated in peroxisomes of n-alkane-grown Candida
      tropicalis [Kurihara, T., Ueda, M., & Tanaka, A. (1989) J. Biochem. 106, 474
      478], while acetoacetyl-CoA thiolase was also shown to be present in cytosol. The
      activity of the enzyme in cytosol was constant irrespective of culture
      conditions, while the peroxisomal enzyme was inducibly synthesized in the alkane
      grown yeast cells. These results indicate that peroxisomal acetoacetyl-CoA
      thiolase participates in alkane degradation, while the cytosolic enzyme is
      associated with other fundamental metabolic processes, probably sterol
      biosynthesis, because this enzyme can catalyze the first step of the sterol
      biosynthesis. 3-Hydroxy-3-methylglutaryl (HMG)-CoA reductase, a key regulatory
      enzyme of sterol biosynthesis, was found to be localized exclusively in
      microsomes of the alkane-grown yeast cells. These results suggest that yeast
      peroxisomes do not contribute to sterol biosynthesis, unlike the case of
      mammalian cells.

PMID- 1363553
TI  - Endothelium-derived relaxing factor contributes to the regulation of endothelial
      permeability.
AB  - To determine whether endothelium-derived relaxing factor (EDRF) contributes to
      the regulation of endothelial permeability, the transendothelial flux of 14C
      sucrose, a marker for the paracellular pathway across endothelial monolayers
      (Oliver, J. Cell. Physiol. 145:536-548, 1990), was examined in monolayers of
      bovine aortic endothelial cells grown on collagen-coated filters. The
      permeability coefficient of 14C-sucrose was significantly decreased by 10(-3) M 8
      Bromoguanosine 3',5'-cyclic monophosphate or by 5 x 10(-6) M glyceryl trinitrate,
      an activator of soluble guanylate cyclase. Depletion of L-arginine from
      endothelial monolayers increased 14C-sucrose permeability from 3.21 +/- 0.59 to
      3.88 +/- 0.50 x 10(-5) cm.sec-1 (mean +/- SEM; n = 6; P < 0.05). The acute
      administration of 5 x 10(-4) M L-arginine to monolayers depleted of this amino
      acid decreased 14C-sucrose permeability from 2.91 +/- 0.27 to 2.52 +/- 0.26 x 10(
      5) cm.sec-1 (n = 11; P < 0.05). 14C-sucrose permeability was increased by 10(-7)
      M bradykinin and this effect was enhanced by the presence of each one of the
      following compounds: 10(-5) M methylene blue, 4 x 10(-6) M oxyhemoglobin, 5 x 10(
      4) M NG-methyl-L-arginine or 5 x 10(-4) M N omega-nitro-L-arginine. These results
      suggest that EDRF contributes to the sealing of the endothelial monolayer and
      that EDRF released by bradykinin acts as a feedback inhibitor attenuating the
      increase in endothelial permeability induced by this peptide. Because endothelial
      cells have the ability to contract and relax and possess guanylate cyclase
      responsive to nitric oxide, our results suggest that EDRF decreases 14C-sucrose
      permeability by relaxing endothelial cells, thereby narrowing the width of
      endothelial junctions.

PMID- 1363554
TI  - Lanthanum influx into cultured human keratinocytes: effect on calcium flux and
      terminal differentiation.
AB  - Trivalent cation lanthanum (La) binds to calcium binding sites of cells and
      either mimics the properties of calcium or inhibits the effects of calcium by
      displacing calcium from its binding sites. Extracellular calcium induces
      differentiation of human epidermal keratinocytes in culture, in part by
      increasing the intracellular calcium levels (Cai). Therefore, in this study we
      determined the effect of La on differentiation and intracellular calcium levels
      of keratinocytes. We observed that La inhibited the production of cornified
      envelopes, a marker for terminal differentiation of keratinocytes. La inhibited
      the calcium requiring envelope cross-linking enzyme, transglutaminase, in a
      direct manner, presumably, by displacing calcium from its binding site on the
      enzyme. La inhibited the influx and the efflux of 45Ca from keratinocytes.
      Paradoxically, extracellular La appeared to increase the Cai levels of
      keratinocytes as measured by the fluorescent probe indo-1. However, subsequent
      experiments revealed that indo-1 bound La with a higher affinity than Ca and
      emitted fluorescence in the same wavelength as the Ca bound form. Using this
      probe, we observed that La enters keratinocytes in a dose-dependent fashion and
      achieves concentrations exceeding 80 nM when the external La concentration is
      raised to 300 microM. This fully accounted for the apparent increase in Cai when
      La was added to the cells. Treatment of cells with ionomycin increased indo-1
      fluorescence maximally in the presence of La indicating influx of La via this Ca
      specific ionophore. Our results indicate that La enters cells and inhibits
      calcium mediated keratinocyte differentiation both by blocking Ca influx and by
      blocking calcium regulated intracellular processes such as transglutaminase
      directed cornified envelope formation.

PMID- 1363555
TI  - The Economics of Hypertension Control. Proceedings of the World Hypertension
      League International Workshop. Barcelona, Spain, September 1991.

PMID- 1363556
TI  - [Surgery for pseudarthrosis of the scaphoid bone performed in Hungary 1988].
AB  - Authors analyse, based on an all-round inquiry, the operations performed for
      pseudarthrosis of the scaphoid in 1988. It was found that 344 of 472 operations
      were reconstructive, 128 palliative. The single types of operation are briefly
      described. They hint at the fact that the operative treatment of scaphoid
      pseudarthrosis in Hungary is carried out mostly in Centers.

PMID- 1363557
TI  - [Statement of the Hungarian Society of Plastic Surgeons on the use of silicone
      breast implants].

PMID- 1363558
TI  - [Anatomical bases of ultrasonic examination of the shoulder joint].
AB  - Authors present the parts of the shoulder that can be represented by ultrasound.
      Beside the rotator cuff of accentuated significance (within this, first of all
      the tendon of the supraspinatus muscle) the subacromial bursa, the tendon of the
      long head of the biceps, the muscle-tendon junction of the infraspinatus muscle
      are analysed. It is stated that the ultrasonography is suitable for a reliable
      representation of the soft tissues, surrounding the shoulder joint, further in
      possession of literary data they see possibility for a very exact judgement of
      the pathological alterations, too.

PMID- 1363559
TI  - [Experience with the surgical management of childhood fractures and epiphyseal
      injuries].
AB  - Authors analyse 1792 fractures in children, treated during 10 years in their
      Department and distributed in age groups. They take the part of conservative
      treatment of the majority, about two third, of fractures in childhood. They
      consider as operative indication certain forms of epiphyseal injuries, the
      dislocated intraarticular fractures, the unstable fractures, certain cases of
      polytrauma and the open fractures.

PMID- 1363560
TI  - [Stabilization of the injured acromioclavicular joint using a new type of
      fixation plate].
AB  - The opinions in the question of transitory fixation of the joint during the
      treatment of the acromioclavicular articulation are rather different. The
      complications of the widely used methods--break of the implant, its tear from the
      bone, the wandering and the disturbances of wound healing--are well known. To
      decrease the number of complications authors have developed a new type of hooked
      plate. The plate is fitted to the anterior surface of the acromial end of the
      clavicle and its hook is fixed from below in the bore hole of the acromion. To
      choose the optimal place of the bore hole a drill guide was prepared. The
      operative method is described and the advantages of the method are summarized.
      The "Debrecen-plate" was used during 2 years in 39 injuries. 35 patients were
      controlled 6-24 months after the operation. Based on the results of the treatment
      a wider use of the method is suggested.

PMID- 1363562
TI  - [Value of osteotomy of the proximal end of the metatarsal base in Kohler II
      disease].
AB  - Authors briefly describe the etiology of Kohler II. disease and the possibilities
      of the operative treatment. The osteotomy of the proximal end of the metatarsus,
      performed by them, the biomechanical basis of the operation, the indication are
      detailed and the favourable experiences gained with this procedure are reported.

PMID- 1363561
TI  - [Overhead extension in delayed diagnosis of congenital hip dislocations in
      children, following failure of treatment with the Pavlik harness].
AB  - Authors report, based on a retrospective examination of 103 dislocated hips of 85
      children, on experiences with the overhead treatment of congenital hip
      dislocations, resistant to Pavlik harness or lately recognized. The results are
      compared with those of 23 hips of 20 children treated with Pavlik harness and
      plaster casts. Follow-up time was 3-15, in average 7 years. It is stated that the
      overhead extension treatment not followed by stiff fixation resulted in 92 per
      cent reduction in resistant and lately recognized hip dislocations. This
      procedure has caused in only 4 per cent severe necrosis of the femoral head with
      lasting consequences. Their experience with Pavlik harness combined with plaster
      cast are unfavourable as in 4 of 23 hips treated subtotal, in another 7 partial
      femoral head necrosis has developed.

PMID- 1363563
TI  - [Measuring the looseness of the knee joint by using the Kt 1000 arthrometer].
AB  - Authors measured the stability in the sagittal plane of the intact knee joints of
      50 young men with the MEDmetric KT 1000 apparatus. The greatest movement during
      the measurements on 100 knees was observed in 25 degrees flexion and during the
      application of force 89N. In 70 degrees flexion the movement was only half of
      that observed in 25 degrees flexion. The difference of the average movements
      measured bilaterally was neither in active nor in passive experiments more than
      0.5 mm. The difference between the average values of the compliance indexes on
      the left and right side was only 0.01 mm. In all measurements the frequency
      distribution of the differences between the two sides was essentially the same.
      The difference between the movements on the two sides did not exceed 2 mm-s in 90
      100 percent of the cases.

PMID- 1363564
TI  - [Experience with the "Oxford" type uni-condylar meniscus- and surface replacing
      knee prosthesis. Preliminary report].
AB  - Authors report on the first implantation of a new type of an unicondylar meniscus
      and surface replacing knee prosthesis in this country. After a brief literary
      review the prosthesis, the instruments developed for the implantation, the
      indications and the early favourable results of their two operations are
      described.

PMID- 1363565
TI  - [Enhancement of the ossification of decalcified bone].
AB  - Authors have proven with previous experiments that the decalcinated bone can be
      used as transplant. In this paper their experiments to increase the osteogene
      capacity of this kind of bone for replacement are described. It is stated that
      with the use of electric after treatment both the speed of the development of new
      bone after bone replacement both the rebuilding on the recipient bone ends may be
      advantageously influenced. With their method the bone defect in the rabbit's
      radius could be healed in four weeks.

PMID- 1363566
TI  - [Experience with the management of scapula fractures].
AB  - Authors have treated 37 fractures of the scapula during 3 years. The questions of
      the aetiology, classification, diagnosis and therapy of this injury are reviewed.
      It is stated that the majority of the scapula fractures heal on conservative
      therapy; in consequence the functional treatment has a leading role. The
      fractures of the articular surfaces with step formation, the fractures of the
      scapular neck process dislocated in a high degree, or unstable fractures of the
      scapular neck combined with the comminutive fractures of the operative therapy
      are assessed. Attention is called to the most frequent operative complications
      and to the possibility of their prevention.

PMID- 1363568
TI  - [Examination of infection and infectivity of open injuries].
AB  - Authors examined the circumstances of bacteriological infection of open fractures
      and large size injuries of the soft tissues. Bacteriological examinations were
      made from the ichor before the primary wound care and immediately after its
      finishing. It is stated that in open injuries there is only a potential
      possibility of infection and with an early wound care its danger can be
      substantially decreased. In the purulent infection after open injuries one has
      always to think on the possibility of secondary hospital infection.

PMID- 1363567
TI  - [Experience with the management of childhood diaphyseal fractures].
AB  - Author reports on experiences gained during 10 years the diaphyseal fractures in
      childhood. Whereas certain types of fracture near to the joints have a generally
      accepted absolute operative indication, the surgery in diaphyseal fractures is
      rarely held to be indicated. Osteosynthesis was performed in 18 per cent of all
      cases. Surgery is thought to be indicated in open fractures, in fractures that
      cannot be reduced or that are unstable, in polytrauma and in bilateral cases. In
      closed fractures plate osteosynthesis, in severe open fractures the fixateur
      externe was found to be the best solution. In certain cases Kuntscher nailing of
      the femur, medullary splinting of the lower arm or diafixation of the lower leg
      are performed in older children.

PMID- 1363569
TI  - [Development of informatics at the Traumatology Department of the University of
      Debrecen].

PMID- 1363570
TI  - [Experience with the Bristow procedure].
AB  - Authors assess the results of 17 Bristow's operations performed in the therapy
      recurrent anterior dislocation of the shoulder. The literature of the subject is
      reviewed, the technical details of the operations are described and the
      possibilities of complications are pointed out. On the basis of literary data and
      their own favourable experiences the wider use of this method is suggested.

PMID- 1363571
TI  - [Fracture of the lower thoracic spine in ankylosing spondylitis].
AB  - Authors report on experiences gained during the treatment of the injury of the
      lower thoracal spine in a 64 year old male patient and review the relating
      literature. As a consequence of the basic disease fractures may occur following
      rather trivial traumas. As all ligaments are calcified a particular unstable
      state will develop following the fracture.

PMID- 1363572
TI  - [Management of agricultural injuries at our department].
AB  - Authors want to call attention with the presentation of 4 cases to the
      significance of the agricultural injuries and to the difficulties of the therapy.
      The importance of the primary wound care is stressed. An adequate excision of the
      wound, debridement and an open wound care are essential in severely crushed,
      soiled cases. Therapy of severely crushed injuries, complicated with multiple
      fractures needs individual weighing and a reconstruction in more sittings.

PMID- 1363573
TI  - [Experience with modular system tumor prostheses].
AB  - Authors elaborated a modular tumor prosthesis by the use of which the bone
      segment lost after the resection of hip, femur, knee and proximal tibial tumors
      can be supplemented in the desired measure. The components of the prosthesis set
      and the field of its use are described. In the last one and half year modular
      tumor prostheses were inserted in 10 patients: in 6 primary bone tumors and 4
      solitary metastases. One shoulder, 5 hip, 3 stiff knee and 1 tibia diaphysis
      supplementing modular prostheses were inserted. In spite of 2 complications the
      initial experiences are encouraging, and in adequate indication the possibility
      of retaining limb and articular function beside good functional results is given.

PMID- 1363574
TI  - [Management of upper arm fractures using a thermoplastic functional brace].
AB  - Authors report on the functional bracing of the fractured humerus. The advantage
      of the method is the preserved muscle and joint function with the use of a brace.
      This means ease for the patient in respect of the personal hygiene and living
      conditions. In elderly patients all other type of fixation around the chest means
      a substantial danger to the patients life because of the breath's movements
      depression.

PMID- 1363576
TI  - [Distally pedicled fasciocutaneous flaps].
AB  - Authors used for the supplementation of the soft parts of the lower extremity
      reversed fasciocutaneous flaps in 8 cases; 6 of them were burned patients. In the
      Hungarian literature no paper on the use of distally pedicled flaps was published
      until now.

PMID- 1363575
TI  - [Results of using bone cement and phenol lavage in the surgical management of
      giant cell bone tumors].
AB  - Authors report on experiences gained with phenol lavage used as adjuvant and
      filling with bone cement in the surgical treatment of giant cell tumors of the
      bone. The effect of the adjuvant therapy was a considerable decrease in the rate
      of relapses: in 11 patients 1 relapse was found only in contrary to the 15
      relapses in the control material (41 per cent) after 36 excochleations. They
      think that with adequate indications both the phenol lavage and filling with bone
      cement are useful supplements to the surgical therapy.

PMID- 1363577
TI  - [Chondromatosis in the metacarpophalangeal joint].
AB  - The case of a 57 year old male patient is described, operated for synovial
      chondromatosis of the third metacarpophalangeal joint of the left hand. The
      pathogenesis and the opinions on the therapy of this disease, described rarely
      because of its localization even in the world literature, are discussed.

PMID- 1363578
TI  - [Incidental scaphoideo-trapezoid arthrodesis instead of Matti operation].
AB  - Author reports on a technical fault during Matti--Russe's operation. The
      corticospongious graft was inserted instead of the pseudarthrosis, in the
      scaphoid-trapezial joint. Because of the scaphoid-trapezial ankylosis developed,
      the persistent pseudarthrosis and the degeneration in the carpal bones the
      freeing of complaints could be reached only by intercarpal arthrodesis and wrist
      denervation, according to Wilhelm.

PMID- 1363579
TI  - [Ventricular hyperkinetic arrhythmias: a current therapeutic problem. The
      possible greater use of beta blockers].
AB  - The therapeutic approach to cardiac arrhythmias is constantly evolving due to our
      improved understanding of their mechanisms and clinico-prognostic implications,
      even if uncertainties and controversies continue to be a marked feature of this
      sector, perhaps more than in any other field of medicine. The frequent finding of
      cardiac arrhythmias in the healthy and cardiopathic population justifies the
      importance which the question of the diagnosis and treatment of cardiac rhythm
      disorders has now assumed, even if, as far as the latter is concerned, the
      aggressive approach has been considerably modified over the past years. This has
      occurred in view of the still unproven value of indiscriminate anti-arrhythmic
      treatment for the purposes of prolonging life. This treatment has only been
      demonstrated to be of value in a few studies in selected subgroups of high-risk
      patients. In addition, it should be underlined that it has been reported that
      anti-arrhythmic drugs may possible aggravate or induce new arrhythmia. This
      potential pro-arrhythmic effect has become increasingly recurrent due to the
      widespread use and diffusion of this category of drugs. Such considerations
      should therefore encourage greater caution in the use of these drugs. Cardiac
      arrhythmias may be benign or life-threatening, symptomatic or asymptomatic; they
      may be a warning sign of sudden death, or be the cause or effect of heart
      failure, be the expression of an acute or chronic heart disease, or the clinical
      manifestation, at a cardiac level, of an extracardiac pathology. Within this
      broad-ranging clinical context, arrhythmia often gives rise to therapeutic
      dilemmas which must be resolved with extreme rationality, taking into account the
      results of all available clinical trials. The results of the Cardiac Arrhythmias
      Suppression Trial (CAST) showed that clinical judgements of therapeutic efficacy,
      made in the absence of carefully controlled studies, are often incorrect. On the
      basis of these findings beta-blocking drugs may find increasing use, since while
      they are not anti-arrhythmic drugs in the strict sense of the term, they are
      safer due to their negligible pro-arrhythmic effect, the lower incidence of
      collateral effects and their proven efficacy in post-infarction. The role of beta
      blockers in the treatment of manifest heart failure should not be over-looked,
      since by countering the deleterious effect of increased catecholamines they may
      improve the prognosis, thus reducing the incidence of sudden death.

PMID- 1363581
TI  - 1st Congress of the French Society of Bone Marrow Transplantation. Bordeaux,
      October 22-24, 1992. Abstracts.

PMID- 1363580
TI  - Lysosomal enzyme activities in frozen, non-cultured chorionic villi for prenatal
      diagnosis of enzymopathies.
AB  - Normal reference values of lysosomal enzyme activities (alpha-glucosidase,
      mannosidase, fucosidase and arylsulfatase-A) were determined in chorionic villi
      obtained from artificial abortion in the first trimester of normal pregnancies
      (gestational weeks 6 to 11). Villi were homogenized comparatively either in
      saline or in Triton X-100 detergent. The alpha-glucosidase, mannosidase and
      arylsulfatase-A enzyme activities significantly diminished if homogenization was
      done in saline instead of Triton-X while the difference in fucosidase activity
      was not significant. Significant correlation was detected between alpha
      glucosidase activity and week of gestation. It is suggested that Triton X-100
      homogenization should be used for the lysosomal enzyme determinations in
      chorionic villi because the solubilization of enzymes from the lysosomes is
      complete in this case than with homogenization in saline.

PMID- 1363582
TI  - Current topic: Hox genes: losses, gains and targets.

PMID- 1363583
TI  - Antipsychotic medication effects on neuropsychological functions.
AB  - The investigator of antipsychotic drug effects on neuropsychological functions
      faces a range of conceptual, methodological, and technical obstacles. Some of
      these hurdles are pointed out in a brief review of existing literature, and a
      more detailed consideration of instrumentation issues is presented. The need for
      hypothesis-driven assessment strategies is highlighted. Interpretive difficulties
      are posed by the polyfactorial nature of the most widely used neuropsychological
      tests, and emphasis is placed on the use and development of methods that enable
      isolation of specific neuropsychological constructs. Examples of this strategy
      are drawn from ongoing work in the Neuropsychology Unit of the Clinical Research
      Center for the Study of Schizophrenia at Hillside Hospital, where hypotheses
      about the behavioral site of action of dopamine agonists and antagonists are used
      to guide the construction of novel computerized tests.

PMID- 1363584
TI  - International Workshop on Clinical Pathology Testing in Preclinical Safety
      Assessment. Proceedings. Washington, D.C., July 27, 1991.

PMID- 1363585
TI  - [Medical treatment of acromegaly. Somatostatin analogs offer a real hope].

PMID- 1363586
TI  - [Activity of gamma-glutamyltranspeptidase in serum and urine of patients with
      polycystic renal disease and hepatic cystic disease].
AB  - The determination of gamma-glutamyltranspeptidase activity was carried out by the
      Rosalka et al. method in the serum and urine in the control group of healthy
      persons (20 cases), in the group of polycystic renal disease and hepatic cystic
      disease (18 patients), and in the group of polycystic renal disease (in 32
      patients in the serum, and in 28 patients in the urine). No significant
      differences were found in the values of the enzyme activity in the studied
      patients in relation to the control group.

PMID- 1363587
TI  - Somatostatin immunopositive neurons in the small intestine of the bullfrog (Rana
      catesbeiana).
AB  - Somatostatin immunopositive neurons in the small intestine of the bullfrog (Rana
      catesbeiana) were studied using immunohistochemistry and surgical denervation of
      the mesenteric nerve. Immunopositive nerve elements were distributed throughout
      the small intestine, including nerve fibers in the myenteric plexus, circular
      muscle layer, submucosal layer, and mucosa. Somatostatin immunopositive nerve
      cell bodies occurred in the myenteric plexus but not in the submucosal layer.
      These cell bodies were surrounded by immunopositive nerve fibers forming basket
      like terminals, and thus some of these cells may be interneurons. After
      denervation of the mesenteric nerve, adrenaline immunopositive nerve fibers
      disappeared almost completely from the small intestine, but no changes occurred
      in the distribution of somatostatin immunopositive neurons. Neurons in the
      coeliac ganglion projecting into the small intestine were adrenaline
      immunopositive but somatostatin immunonegative. The results indicate that
      somatostatin immunopositive neurons in the small intestine of the bullfrog are
      primarily intrinsic in origin.

PMID- 1363588
TI  - [State of the pancreatic insular apparatus in experimental diabetes mellitus with
      varying degrees of severity in the rat].
AB  - The interrelationship between endocrine cells of the Langerhans islands in
      experimental diabetes provoked in female Wistar rats are studied. The content of
      the insulin in B-cells, glucagon in A-cells and somatostatin in D-cells was
      determined by method of indirect immunofluorescence with the use of monoclonal
      antibodies and antiserum. It is established that an decrease of the insulin
      content in B-cells is followed by an increase of glucagon in A-cells and that of
      somatostatin in D-cells. The increase of the glucagon content is proportional to
      glycemia level and to the decrease of the insulin in B-cells.

PMID- 1363589
TI  - Restriction fragment length polymorphism (RFLP) analysis provides evidence for a
      high degree of homology of mitochondrial DNAs from rat hepatomas versus normal
      rat livers.
AB  - Where differences have been reported between tumor and normal mitochondrial DNA
      (mtDNA), they have generally involved limited modifications of the genome (Taira
      et al., Nucleic Acids Res. 11:1635, 1983; Shay and Werbin, Mutat. Res. 186:149,
      1987). However, Corral et al. (Nucleic Acids Res. 16:10935, 1988; 17:5191, 1989)
      observed recombination between cytochrome oxidase subunit I (COI) and NADH
      dehydrogenase subunit 6 (ND6), two genes normally on opposite sides of the
      circular mitochondrial genome. In rat hepatoma mtDNA COI and ND6 were reported to
      be separated by only 230 base pairs (Corral et al., 1988, 1989). We have
      performed RFLP analysis on mtDNA from normal rat livers and rat hepatomas, using
      COI and ND6 probes. Additional experiments compared end-labeled DNA fragments
      produced by EcoRI and HindIII digestion of mtDNA. These studies failed to provide
      any evidence for genetic recombination in rat hepatoma mtDNA, even in the same
      cell line used by Corral et al. Rather, they support the conclusion that mtDNA
      from tumor and normal tissues exhibits a low degree of heterogeneity.

PMID- 1363590
TI  - Molecular characterization of the smallest secondary constriction region (qh) of
      human chromosome 16.
AB  - We report the smallest secondary constriction region (h) in human chromosome 16.
      The cytochemical, cytogenetic, and molecular techniques revealed the complex
      heterogeneity of heterochromatin observed in this region. The heteromorphisms can
      be found due to the variation in centromeric (c) region alone or in combination
      with the h region. Routine selective staining techniques fail to differentiate
      the C region from the h region. However, the fluorescence in situ hybridization
      technique clearly demonstrated that the centromere of chromosome 16, which is
      composed of 340-base-pair dimers arranged in a tandem array of 1.7-kb higher
      order repeat units, is not heteromorphic in the present case, but other molecular
      cytogenetic techniques demonstrated the presence of a very small h region. The
      evolution of heterochromatin of this region is discussed.

PMID- 1363591
TI  - [Neuroleptics and antidepressants].

PMID- 1363592
TI  - The aminoquinazoline group as a replacement for the salicylamide group: the
      design and synthesis of a novel highly selective beta 1 adrenoceptor partial
      agonist.
AB  - The high potency at beta 1 receptors, excellent selectivity (beta 1/beta 2) and
      high degree of agonism displayed by compounds such as 1 is believed to be due in
      part to the salicylamide side chain. Two conformations of salicylamide are known
      to exist in the crystal state (2 and 3), but ab initio calculations suggest that
      in the absence of crystal packing forces 2 should be more stable. The
      aminoquinazoline group was judged to be a good replacement for salicylamide in 1,
      and consequently the oxypropanolamine derivative 4 was prepared. 4 shows
      extremely high potency at the beta 1 receptor, and excellent beta 1/beta 2
      selectivity. It has comparable in vitro activity to 1, although it displays a
      lower degree of agonism. These results suggest that in this system
      aminoquinazoline appears to be an excellent mimic of the salicylamide group.

PMID- 1363593
TI  - [Lectures of the 26th annual meeting of the German Society for Medical and
      Biomedical Engineering. Hannover, 1-3 October 1992].

PMID- 1363594
TI  - Cytokines and HIV infection.

PMID- 1363595
TI  - Effects of interleukin-8 on suppression of human lymphocyte polarization and
      migration by anti-LFA-1 antibody.
AB  - We investigated the role of lymphocyte function-associated antigen 1 (LFA-1) in
      human T cell polarization and migration assay by using monoclonal antibody
      specific to beta chain (CD18) and alpha chain (CD11a). T cell polarization in
      response to fetal calf serum (FCS) and colchicine was suppressed by the addition
      of CD18 and CD11a antibodies. Furthermore, T cell migration in response to
      lymphocyte chemotactic factor (LCF) and casein was markedly depressed by the
      addition of CD18 and CD11a antibodies. Additional studies to evaluate effects of
      interleukin 8 (IL-8) on polarization and migration of T cells preincubated with
      CD18 or CD11a antibody showed that IL-8 restored the capability of migration of T
      cells, whereas did not restore polarization activity of such cells. These studies
      indicate that LFA-1 plays a role in the polarization and migration of T cells and
      that IL-8 may positively interfer with LFA-1-adhesion molecules.

PMID- 1363596
TI  - [The regulation of human cardiac activity during the cyclical change of
      barometric pressure under sealed-cabin conditions].
AB  - A cyclic change of barometric pressure from 790 to 720 mm Hg once a day to twice
      within 3 days under sealed conditions results in a functional rearrangement of
      the mechanisms to control cardiac activity which cause the predominance of
      vagotonic responses determined by a decrease of the body reserves and its
      asthenization. At the beginning of staying under pressurized conditions (2nd
      week) it appears as an occurrence of meteorotropic responses (in 13% of subjects
      tested) and at the end of living in pressurized conditions (9th week) as a
      significant decline with a change ("removal") in: pressure, index of strain,
      vegetative index of rhythm, index of regulation processes, index of vegetative
      equilibrium and as an increase in the number of individuals responding to a
      cyclic change of barometric pressure up to 44% which is indicative of a moderate
      relationship between manifestation rate of these sensations and an effect
      duration of a given factor.

PMID- 1363597
TI  - Very low calorie diets and recently developed anti-obesity drugs for treating
      overweight in non-insulin dependent diabetics.
AB  - Weight reduction in non-insulin dependent diabetes mellitus (NIDDM) patients
      improves metabolic control, reduces cardiovascular risk factors, has blood
      pressure lowering effects and improves the well-being of the patient. This paper
      describes the role of very low calorie diets (VLCD), exercise, beta-adrenergic
      drugs and serotoninergic agents in the treatment of overweight in NIDDM. VLCD
      reduce body weight and improve glucose metabolism. Physical exercise programmes
      in addition to dietary restriction substantially contribute to weight loss and
      metabolic control in NIDDM. New specific beta-adrenergic agents, exhibiting
      virtually no beta 1 or beta 2 activity, increase energy expenditure and weight
      loss probably by enhancement of the basal metabolic rate. The target tissue in
      humans of this beta-adrenergic effect is as yet unknown. These drugs seem to
      enhance weight loss when used in combination with (very) low calorie diets
      compared to dietary restriction alone. Serotoninergic drugs reduce body weight by
      decreasing appetite, in particular for carbohydrates. Furthermore these drugs
      seem to improve insulin receptor sensitivity.

PMID- 1363598
TI  - Production of phytochelatins in Polygonum cuspidatum on exposure to copper but
      not to zinc.
AB  - We studied cellular resistance to copper of plant cells Polygonum cuspidatum.
      When callus of P. cuspidatum was incubated on medium containing 100 microM cupric
      sulfate, the callus grew as well as the control callus did. The copper content of
      the callus, however, was elevated to a similar level of the medium. When cell
      extracts of callus exposed to 100 microM cupric sulfate were fractionated by gel
      filtration chromatography, a specific copper peak was eluted at the region of
      molecular weights between 4000 and 1000. Since an appearance of the copper
      containing materials was inhibited by buthionine sulfoximine and the partially
      purified copper-containing materials contained only three amino acids: glutamic
      acid, glycine and cystine, the materials were supposed to be gamma-glutamyl
      peptides phytochelatins. Callus of P. cuspidatum synthesized phytochelatins from
      50 microM cupric sulfate and maximally at 100-150 microM cupric sulfate. When
      induction of phytochelatins by another heavy metal, zinc, was analyzed, the
      callus, however, did not synthesize phytochelatins on exposure to zinc sulfate up
      to 1 mM. These findings suggested that phytochelatins were required for
      resistance to copper but probably not to zinc in the plant cells.

PMID- 1363599
TI  - [New information about the biomechanics of fracture fixation].
AB  - The better knowledge of the biomechanics of bone tissue and fracture healing
      resulted in the development of the AO principles and its methods of treatment. I
      have demonstrated on the femora of rabbits that the consequence of progressive
      dynamization versus the current unchanging stability of fracture fixation was a
      more rapid healing. According to our knowledge the more elastic, dynamizating or
      dynamizable fixation of the fracture are the methods of future. The new
      biodegradive implantates make not only their removal superfluous but help the
      fracture healing, too.

PMID- 1363600
TI  - [Double dislocation on the same finger (based on author's own cases as well as
      data from the literature)].
AB  - Author describes now the third time this very rare injury. New cases are
      demonstrated and the knowledge originating partly from all other authors, partly
      developed by himself is summarized.

PMID- 1363601
TI  - [Three-dimensional CT studies of pelvic fractures].
AB  - Authors use in the diagnosis of fractures of the pelvis a three dimension
      programme developed by them to the tomographic apparatus of the Siemens Somatom
      CR computer. With the demonstration of a few pictures of their own they call
      attention to the possibility of diagnosis given by the 3D-CT programme. On the
      basis of their experiences the advantages and disadvantages of this modern
      imaging method are summarized.

PMID- 1363602
TI  - [Diagnosis and management of hand injuries caused by foreign bodies].
AB  - The authors survey the possibilities of diagnosis of the frequent injuries of the
      hand caused by foreign bodies. It is proven by them that almost all foreign
      bodies can be demonstrated using radiological methods (native picture, ultrasound
      examination, xeroradiography, CT, MRI). They support the immediate surgical care
      in the therapy of injuries caused by foreign body, they deal however with the
      problems of the later therapy, too. Their opinion is backed up by the
      demonstration of case reports.

PMID- 1363603
TI  - [Surgical treatment of hallux valgus by peg osteotomy].
AB  - Authors describe a method of therapy of hallux valgus not yet published in this
      country. Its advantage is that as a consequence of the shortening of the proximal
      phalanx the tension of the soft tissues is decreased and as a final result the
      movement occurs between the original cartilaginous surfaces.

PMID- 1363604
TI  - [Management of metatarsalgia using Helal's method for metatarsal osteotomy].
AB  - Authors report on the result of Helal's metatarsal osteotomies performed on 62
      feet of 48 patients for metatarsalgia. In 85 per cent the result proved to be
      excellent, in 15 per cent there was no improvement. Analysing the causes of the
      postoperative complaints they call attention to the overload of the marginal
      arches and to the metatarsalgia developing on the non osteotomized neighbouring
      arch. These complaints appeared in 1/3 of their material and could be generally
      well influenced with conservative treatment.

PMID- 1363605
TI  - [Experience with the AGC-2000 type bicondylar surface-substituting knee
      prosthesis].
AB  - Authors report on the first use of bicondylar surface substitution knee
      prosthesis of a new type. The prosthesis and the instruments developed for
      implantation are demonstrated. In the first five operations the appropriateness
      of the implantation instruments, the exactness of their handling, the assortment
      of the series of prosthesis have met the plus which, compared to the types known
      until now, can secure the exactness of the operation and improve the ratio of the
      lasting good results.

PMID- 1363606
TI  - [Osteosynthesis of femoral neck fractures by double-cannulated screws
      (preliminary report)].
AB  - Authors report on a new osteosynthesis based on the double nailing of femoral
      neck fracture and screwing, and developed from the "Uppsala" double screwing. The
      preliminaries of the double cannulated screwing method, its advantages, the
      experiences gained in 30 cases operated in one year and the early results are
      described.

PMID- 1363608
TI  - [Posterior dislocation of the median end of the clavicle].
AB  - Authors discuss, based on the experiences gained in the operative treatment of
      posterior sternoclavicular dislocation in two patients, the frequency, the
      symptoms, the classification, the diagnosis and treatment of this rare injury.
      One of the two injuries was fresh the other inveterated. No description of the
      operative treatment of similar injuries was found in the literature of this
      country. Finally the importance of the early recognition and the definitive
      treatment of this rare dislocation are stressed.

PMID- 1363607
TI  - [Problems of rehabilitation after femoral neck fractures in Hungary and possible
      solutions].
AB  - Authors examined the results of the 4 months rehabilitation of 753 cases of hip
      fractures treated in one year in their Institute. It was stated that a
      significant part of the patients had to be discharged too early. It is
      contributed to the inadequacy of the rehabilitation possibilities of the patients
      that 3/4 of those living after 4 months have complaints, only half of them can
      leave their flat, only 1/5 walks without a stick and 1/3 with one stick. On the
      basis of Swedish experiences they see the possibility of improving their results
      in a closer cooperation with the primary health care.

PMID- 1363609
TI  - [Acromioclavicular dislocation associated with fracture of the coracoid process].
AB  - The joining of the acromioclavicular dislocation and the fracture of the coracoid
      process is rather rare. The number of cases described in the world literature is
      under 20, in this country no such case was described yet. Author reports on a
      case treated with operation, that healed with good result. The viewpoints of the
      diagnosis and treatment of this injury are reviewed. The results of the
      conservative and operative treatment are hitherto equally favourable. Author
      thinks the operative treatment of injuries with complete dislocation reasonable.

PMID- 1363611
TI  - [Emergency in-hospital care of polytraumatized patients].

PMID- 1363610
TI  - [Arthrosis following knee joint instability and its surgical prevention].
AB  - Authors describe the more important injuries that must be corrected by all means
      during the operative treatment of the acute instability of the knee joint to
      prevent later arthrosis. They call attention to the fact that in the treatment of
      the acute instability of the knee joint the prevention of the arthrosis can be
      realized only with a reconstructive operation, performed in time and with modern
      technique. The biomechanical causes of the arthrosis, developing during the
      persistent instability are analysed. The extraarticular operative methods used by
      them in chronic cases are described.

PMID- 1363612
TI  - [Femoral neck fracture--selection of treatment method].
AB  - Authors followed for 4 months the life of 753 patients with femoral fractures of
      the hip and state, that with an extension of the operative indication the
      hospital mortality was decreased to the half during 15 years in spite of the
      further rise of the age. It is contributed first of all to the inadequacy of the
      rehabilitation that the later mortality is high and it is the double of that in
      the hospital: not more than 3 of 4 injured reaches the 4 months control.

PMID- 1363613
TI  - Environmental aspects in the aluminium industry. Proceedings of 2nd National
      Congress. Venice, Italy, 6-7 May 1991.

PMID- 1363614
TI  - Substance abuse. Pointing out the risk.

PMID- 1363615
TI  - Substance abuse. From ecstasy to agony.

PMID- 1363617
TI  - Neurotransmitters and the pharmacology of the suprachiasmatic nuclei.
AB  - The suprachiasmatic nucleus is the major component of the biological clock
      responsible for the generation and the regulation of circadian rhythms in
      behavioral and physiological functions. The SCN acts as an endogenous circadian
      pacemaker that becomes entrained to the light/dark cycle. Although many
      neuropeptides and neurotransmitters have been localized within and around the
      SCN, their role in the generation of the circadian signal still has to be
      elucidated. There are some data about the transmitters that are involved in the
      mechanism of entrainment. The way the SCN modulates the homeostatic control
      systems that are involved in the control of behaviour, also needs more
      clarification.

PMID- 1363616
TI  - Modulation of the 5-HT1C receptor-mediated behavior by 5-HT2, but not 5-HT1A,
      receptor activation.
AB  - The effects of 5-HT1A-receptor agonists 8-hydroxy-2-(di-n-propylamino) tetralin
      (8-OH-DPAT) and gepirone, a 5-HT1A/5-HT2-receptor agonist 5-methoxy-N,N
      dimethyltryptamine (5-MeODMT) and a 5-HT2-receptor agonist (+-)1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropane ((+/)DOI) on the 5-HT1C-receptor-mediated exploratory
      hypoactivity in rats, induced by m-trifluoromethylphenylpiperazine (TFMPP) or m
      chlorophenylpiperazine (m-CPP), were studied in the open field test. (+/-)DOI
      attenuated the effects of TFMPP and abolished those of m-CPP (not dose
      dependently). 5-MeODMT showed a weak antagonistic action only at one,
      intermediate dose. The effects of TFMPP or m-CPP were not changed by 8-OH-DPAT or
      gepirone. At the same time, 8-OH-DPAT, gepirone, 5-MeODMT and (+/-)DOI themselves
      practically did not change the exploratory activity of rats. The obtained results
      permit an assumption that a functional interaction exists between 5-HT1C- and 5
      HT2-receptors, but not between 5-HT1C- and 5-HT1A-ones.

PMID- 1363618
TI  - Relationship of protease-resistant protein, scrapie-associated fibrils and
      tubulofilamentous particles to the agent of spongiform encephalopathies.
AB  - Tubulofilamentous particles and scrapie-associated fibrils (SAF) are
      ultrastructural markers, while protease-resistant protein (PrP) is a molecular
      biological marker for all spongiform encephalopathies. Review of all published
      work has suggested that PrP molecules aggregate to form a three-dimensional SAF.
      Further reports have suggested that a single-stranded DNA wraps round SAF and
      acquires an outer protein coat to form tubulofilamentous particles. As incubation
      period increases in the infected animals, larger amounts of PrP molecules are
      committed to form SAF, interfering with the normal supply of PrP to cell
      membranes which become disrupted and eventually fragment, resulting in vacuoles
      typical of those found in spongiform encephalopathies.

PMID- 1363620
TI  - [World day against AIDS].

PMID- 1363619
TI  - Scrapie-associated tubulofilamentous particles in human Creutzfeldt-Jakob
      disease.
AB  - Scrapie-associated fibrils (SAF) were demonstrated by a simple negative staining
      method for electron microscopy from fresh and frozen brains with naturally
      occurring human Creutzfeldt-Jakob disease (CJD). The findings confirm that SAF
      occur as an internal part of a larger three-layer particle. The two outer coats
      of SAF can be disrupted by detergent alone or can be digested in two stages by a
      combination of proteolytic enzymes and subsequent treatment with DNase and mung
      bean nuclease. Examination of thin sections from the cerebral cortex of brains
      from patients with CJD revealed the presence of 26-30-nm diameter
      tubulofilamentous particles, identical to those previously described in natural
      scrapie of sheep and bovine spongiform encephalopathy and also in experimentally
      induced scrapie in mice and hamsters and CJD-infected mice and chimpanzees. Thus,
      it would appear that the particles are not contaminants passaged in experimental
      animals.

PMID- 1363621
TI  - Simultaneous occurrence of monoclonal gammopathy and acute secondary leukemia
      with overexpression of P-glycoprotein.
AB  - A 52-year-old woman, previously treated with chemo- and radiotherapy for
      Hodgkin's disease, developed an acute non-lymphoid leukemia and, contemporarily,
      an IgG-kappa paraproteinemia. Cytogenetic analysis showed a major clone,
      representing 90% of observed metaphases, with monosomy of chromosomes 5 and 14.
      In addition, leukemic cells exhibited a high expression of the P-glycoprotein, a
      transmembrane glycoprotein involved in the multidrug-resistance mechanism.
      Possible explanations for this cluster of findings are provided.

PMID- 1363623
TI  - Interrelationships of endoplasmic reticulum, mitochondria, intermediate
      filaments, and microtubules--a quadruple fluorescence labeling study.
AB  - To study the interrelationships of endoplasmic reticulum, mitochondria,
      intermediate filaments, and microtubules, we have developed a quadruple
      fluorescence labeling procedure to visualize all four structures in the same
      cell. We applied this approach to study cellular organization in control cells
      and in cells treated with the microtubule drugs vinblastine or taxol. Endoplasmic
      reticulum was visualized by staining glutaraldehyde-fixed cells with the dye 3,3'
      dihexyloxacarbocyanine iodide. After detergent permeabilization, triple
      immunofluorescence was carried out to specifically visualize mitochondria,
      vimentin intermediate filaments, and microtubules. Mitochondria in human
      fibroblasts were found to be highly elongated tubular structures (lengths up to
      greater than 50 microns), which in many cases were apparently fused to each
      other. Mitochondria were always observed to be associated with endoplasmic
      reticulum, although endoplasmic reticulum also existed independently.
      Intermediate filament distribution could not completely account for endoplasmic
      reticulum or mitochondrial distributions. Microtubules, however, always
      codistributed with these organelles. Microtubule depolymerization in vinblastine
      treated cells resulted in coaggregation of endoplasmic reticulum and
      mitochondria, and in the collapse of intermediate filaments. The spatial
      distributions of organelles compared with intermediate filaments were not
      identical, indicating that attachment of organelles to intermediate filaments was
      not responsible for organelle aggregation. Mitochondrial associations with
      endoplasmic reticulum, on the other hand, were retained, indicating this
      association was stable regardless of endoplasmic reticulum form or microtubules.
      In taxol-treated cells, endoplasmic reticulum, mitochondria, and intermediate
      filaments were all associated with taxol-stabilized microtubule bundles.

PMID- 1363622
TI  - Isolation and characterization of a cDNA encoding a synaptonemal complex protein.
AB  - A gene encoding a 65-kilodalton antigen of the rat synaptonemal complex, SC65,
      has been cloned by screening rat testis lambda gt11 and lambda ZAPII cDNA
      expression libraries using polyclonal antibodies against rat synaptonemal complex
      proteins. The longest open reading frame, initiating at an ATG codon in the cDNA,
      encodes a protein of 431 amino acids, with a relative molecular mass of 50,000.
      Immunological analysis locates the SC65 gene product on the synaptonemal complex
      between the pairing faces of the parallel aligned cores of homologous chromosomes
      in spermatocytes. Of the rat tissues examined, the SC65 gene is transcribed in
      testis, brain, and heart at similar levels, and in the liver at a much lower
      level. The DNA sequence extending about 80 base pairs downstream of the
      translation termination codon has 93% similarity to the identifier sequence
      present in the rat genome in 1 x 10(5)-1.5 x 10(5) copies and in cDNA clones of
      precursors of brain-specific mRNAs. The amino acid sequence encoded by the SC65
      gene contains an acidic region in the C-terminal domain of the protein, potential
      glycosylation sites, and at least one possible phosphorylation site. The protein
      shows no overall similarity to proteins of known function, nor is there
      similarity to protein sequences present in GenBank or EMBL data bases.

PMID- 1363624
TI  - Body axis determination during early development in amphibians.
AB  - The specification of the main axes of the body is a phenomenon based on cell
      communication and is among the early crucial events of embryonic development.
      Upon fertilization, the amphibian egg reorganizes its cytoplasmic content,
      leading to the establishment of the future dorsal-ventral axis of the body.
      Heterogeneous distribution of maternal components confers cellular
      regionalization after only a few mitoses. Development up to the 4000-cell stage
      proceeds almost entirely on maternal materials, and during this period there is
      remodeling of the chromatin to set up specific gene expression in various regions
      of the embryo. The zygote at this stage has already undertaken cellular
      interactions leading to mesoderm formation and regionalization. Dorsal mesodermal
      components then induce the formation of the Spemann's organizer, a structure
      directly involved in the specification of the anterior-posterior axis of the
      embryo (head to tail). Molecular analysis of these phenomena has allowed the
      identification of growth-factor-like and transcription-factor-like proteins that
      have characteristics typical of specification factors. We will review the recent
      advances on these molecules and will also discuss the putative role of retinoic
      acid as a posteriorizing agent.

PMID- 1363625
TI  - [Hypertension and arteriosclerosis].
AB  - Arterial hypertension is a major risk factor for atherosclerosis. The mechanisms
      involved include elevation of blood pressure, increased velocity of the sphygmic
      wave and increased blood flow turbulence. These hemodynamic features however do
      not fully explain the link between hypertension and atherosclerosis. An important
      role is also played by humoral factors including catecholamines, the renin
      angiotensin-aldosterone system, serotonin, endothelin, platelets and endothelium
      derived growth factors. Furthermore in the last few years great relevance has
      been attributed to hyperinsulinemia (accompanied by hypercholesterolemia and
      hypertriglyceridemia) that is frequently found in hypertensive subjects. Several
      recent reports on the antiatherogenic effect of some antihypertensive agents that
      could slow down the progression of atherosclerotic lesions in hypertensive
      subjects are promising.

PMID- 1363626
TI  - [New aspects of therapy in hemicrania].
AB  - Within the pharmacological treatment of migraine it is possible to distinguish
      treatment of attacks and prevention therapy. The aim of attack treatment is to
      stop pain and accompanying symptoms, or at least to make them more tolerable,
      whereas the aim of prophylaxis is to reduce the frequency and possibly the
      severity and duration of the residual episodes. The choice to initiate either
      treatment, or both, is based on quantitative criteria, such as attack frequency
      (if greater than 2-3 per month, prophylaxis treatment is recommendable) and on
      qualitative features, like the degree of disability, the response and the
      tolerance of the patient to attack treatment. Prophylaxis treatment has not
      achieved any improvement since 1981, when propranolol was first utilized. The
      knowledge of the mechanisms of action of drugs used in prophylaxis, as well as
      their results, are at a standstill. Even with the newer calcium channel
      antagonists and beta-blockers we achieve a 50% reduction of attacks in less than
      half of subjects treated. On the other hand, we had important news in the
      treatment of migraine attacks. Sumatriptan, a selective agonist of serotonin
      receptors, represents a therapeutic novelty due both to the results obtained and
      to the studies that have been stimulated on the pathogenesis of migraine. New
      therapeutic perspectives are now opening and hopefully thanks to the cooperation
      of basic and clinical scientists, they might become a reality in a short time.

PMID- 1363628
TI  - Epidemio-entomological survey on malarial vector mosquitoes in Kyongbuk, Korea.
AB  - In order to determine population dynamics of Anopheles sinensis, a survey based
      on average number of female mosquitoes per trap-night was carried out during the
      period of 5 years from 1987 to 1991. A. sinensis first appeared between the 2nd
      and 20th April, and were trapped in large number between the 5th and 12th July.
      The number of trapped mosquitoes began to decrease from mid-August, and a few
      were collected until mid-November, each year. The average number of A. sinensis
      in July was 542.6 per trap-night in 1987, but in 1989 increased abruptly to
      1,331.4, and then decreased to considerably lower levels, 271.9 in 1990 and 372.1
      in 1991. The nocturnal activity of A. sinensis to attack humans was found to
      become active in the early night, and it was gradually decreasing at mid-night,
      however, then slightly increasing toward dawn. The immature stage of A. sinensis
      in the rice paddies was first found in the correlation pattern with peak adult
      densities in early July. The highest larval density of A. sinensis in the study
      area was 21,226 x 10(3) in early July 1990. The larval A. sinensis showed high
      resistance level and resistance ratios against 3 kinds of organo-phosphorous
      compounds, diazinon, malathion, and fenitrothion, but low resistance against
      fenthion. The present results indicated that the population density of A.
      sinensis in Kyongbuk area is decreasing over the five-year from 1987 to 1991.

PMID- 1363627
TI  - Expression of alpha 6 beta 1 integrin, the laminin receptor, on subsets of normal
      murine lung fibroblasts and its upregulation by the inflammatory cytokines IFN
      gamma and TNF-alpha.
AB  - The purpose of this investigation was to ascertain whether the alpha 6 integrin
      subunit was present on normal murine lung cells and fibroblasts, and if so, to
      determine the identity of the beta subunit coordinately expressed with alpha 6
      and whether or not these integrin subunits could be regulated by cytokines.
      Previously, our laboratory isolated populations of Thy 1+ and Thy 1- fibroblasts
      from normal murine lung tissue. These cells differed in surface marker expression
      and in response to, and production of, pro-inflammatory cytokines. Research
      defining the properties of these two populations has led to the hypothesis that
      unique groups of fibroblasts exist within the murine lung. Though alpha 6 beta 1
      is known to be expressed by platelets, lymphocytes, and epithelial cells, its
      presence and regulation on lung fibroblast subsets has not been explored. We now
      report the following findings: 1) the laminin receptor, alpha 6 beta 1, is
      present on 20-30% of freshly isolated normal murine lung cells in all three
      murine strains tested; 2) established Thy 1+ and Thy 1- murine lung fibroblast
      subsets and clones constitutively express alpha 6 beta 1 at varied levels; and 3)
      alpha 6 beta 1 expression on fibroblast lines and clones can be upregulated by
      treatment with IFN-gamma or TNF-alpha. Since these T cell and macrophage derived
      cytokines are known to be present during an inflammatory response, upregulation
      of alpha 6 beta 1 expression may facilitate recruitment and retention of lung
      fibroblasts in regions undergoing repair.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363629
TI  - Proceedings of the 1st European Symposium on Telepathology. Heidelberg, July 20
      21, 1992.

PMID- 1363630
TI  - The effect of alpha-2 agonists and antagonists on the upper urinary tract of the
      rat.
AB  - We examined the effect of the selective alpha-2 agonist dexmedetomidine and
      antagonist atipamizole on the upper urinary tract, renal pelvic pressure and
      ureteral peristalsis. Experiments were performed on twelve Sprague-Dawley female
      rats weighing 275-323 grams, with administration of urethane (1.2 micrograms/kg).
      Ventilatory support was provided through a tracheotomy. A continuous normal
      saline infusion was maintained through the left iliac vein at a rate of 2.5
      ml/hr. Arterial pressure was measured at the left iliac artery, which was
      cannulated with a PE-100 tube connected to a pressure transducer. A mid-line
      incision was then made from the xyphoid to the symphysis to expose the left
      kidney, both ureters, and the bladder. The bladder was intubated and drained to
      avoid bladder pressure increase. Measurements of urine output rate were made from
      the right ureter and renal pelvic or ureteral pressure was measured using a
      nephrostomy placed into the pelvis. A ureterostomy was produced by introducing
      another catheter, into the upper segment of the left ureter for ureteral pressure
      measurements. The rats were divided into two groups as follows: 1)
      dexmedetomidine group (n = 6); injected intravenously with 2 micrograms/kg of
      dexmedetomidine dissolved in 0.5 ml saline. 2) atipamizole group (n = 6);
      injected intravenously with 2 micrograms/kg of atipamizole dissolved in 0.5 ml
      saline. Ureteral peristaltic frequency, baseline pressure, and contraction
      amplitude were compared before, after, and between the bolus injections of 2
      micrograms/kg dexmedetomidine (n = 6) or 2 micrograms/kg atipamizole (n = 6) in
      0.5 ml saline. The results showed that dexmedetomidine at 2 micrograms/kg
      produced a significant decrease in arterial pressure and an increase in urine
      output from 1.2 + 0.8 to 3.6 + 1.2 ml/min. There was no effect on the baseline
      pelvic pressure of 6.8 + 1.2 cmH2O or amplitude of the renal pelvic contractions:
      3.5 + 0.6 cmH2O. The frequency of pelvic contractions was reduced from 0.37 +
      0.03 to 0.27 + 0.02 Hz. Atipamizole at 2 micrograms/kg produced a significant
      reduction in urine flow rate of 1.1 + 0.8 to 0.6 + 0.2 ml/min. Atipamizole also
      showed no significant effects on baseline pelvic pressure or frequency, but
      increased the amplitude of pelvic contractions from control values of 3.0 + 0.9
      to 3.4 + 0.9 cmH2O. Dexmedetomidine reduced both the baseline ureteral pressure
      of 8.5 + 2.4 and peristaltic contraction pressure of 11.5 + 2.3 cmH2O in 4/6
      rats. Atipamizole reduced base-line ureteral pressure and increased peristaltic
      rate.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1363631
TI  - Inhalant allergens in asthmatic children in Taiwan: comparison evaluation of skin
      testing, radioallergosorbent test and multiple allergosorbent chemiluminescent
      assay for specific IgE.
AB  - The multiple allergosorbent chemiluminescent assay (MAST-CLA) is a method for
      measuring total and allergen-specific IgE in human serum by a chemiluminescent
      immuno-enzymatic system. To compare the results of MAST tests with those of
      radioallergosorbent (RAST) and skin tests as an adjunct to the diagnosis of
      inhalant allergens in Taiwan, 195 asthmatic children, aged 5 to 15 years, were
      studied. All MAST tests had valid positive and negative control threads. The most
      important allergens in our patients were the two mite species: Dermatophagoid
      pteronyssinus and Dermatophagoid farinae (87.5% and 82.1%, respectively). There
      were also large responses (MAST-CLA class > or = 2) to the cockroach mix
      (28.45%), Alternaria (24.3%), and Eucalyptus (32.6%). The individual efficiency
      percentage between MAST-CLA and skin tests was D. pteronyssinus 91%, D. farinae
      88%, cockroach mix 85%, feather mix 75%, dog dander 64%, Candida 75%, Aspergillus
      79%, Alternaria 88%, ragweed mix 62% and Eucalyptus 76%. Comparison of the
      results of allergen-specific IgE measured by MAST-CLA and RAST were also
      significantly correlated for all four allergens (D. farinae, Candida, Alternaria
      and grass mix, r = 0.79-0.92). MAST-CLA was randomly duplicated and proven
      reproducible in 89% of the tests. Changes between positive and negative results
      occurred in only 3.6% of the tests. MAST-CLA is a simple in vitro test for
      specific IgE to 35 allergens, which compares favorably with RAST. It is concluded
      that MAST-CLA and RAST are similar in their ability to measure allergen-specific
      IgE, and correlate equally well with skin tests and clinical history in asthmatic
      children.

PMID- 1363632
TI  - Blood levels of platelet-activating factor in endotoxin-sensitive and endotoxin
      resistant mice during endotoxemia.
AB  - Platelet-activating factor (PAF) is a phosphoglyceride secreted by a variety of
      cells and has been implicated in endotoxin toxicities. To further confirm its
      role in endotoxin-induced tissue injuries and death, we conducted an experiment
      on endotoxin-resistant (C3H/HeJ strain) and endotoxin-sensitive (C3H/HeN strain)
      mice. The experiment consisted of three parts: 1) the LD50 of endotoxin from E.
      coli 0127:B8 cells was quantitated in C3H/HeN mice; 2) the lethality of PAF in
      C3H/HeJ mice at a dose lethal to C3H/HeN mice was determined; and 3) the blood
      levels of PAF in C3H/HeJ and C3H/HeN mice were measured after a dose of endotoxin
      lethal to the C3H/HeN strain was injected. PAF contained in the blood samples was
      extracted by a solid phase procedure and assayed by a radioimmunoassay method.
      The results showed that endotoxin-resistant and endotoxin-sensitive mice were
      equally susceptible to death induced by the same lethal dose of PAF. After
      injection with endotoxin, the blood PAF levels in C3H/HeN mice increased
      significantly (p < 0.01) at 60 minutes and 90 minutes, with a peak level three
      times that of the control group. The blood PAF levels in C3H/HeJ mice, however,
      remained unelevated throughout the experiment. The timing of the occurrence of
      the peak blood PAF level in the C3H/HeN mice corresponded with the emergence of
      their illness from the endotoxin injection. These findings shed new light on our
      understanding of the resistant mechanisms of C3H/HeJ mice to bacterial endotoxin
      and affirm the possible role of PAF in mediating endotoxin toxicities.

PMID- 1363634
TI  - Relationships between age, sex, anthropometry and bioelectrical impedance.
AB  - To establish the relationships between age, sex, anthropometric measurements and
      bioelectrical impedance, 446 healthy subjects (242 men and 204 women), aged 17 to
      88 years, were enrolled in our study. Anthropometric parameters included body
      weight, height, body mass index (BMI), skinfold thickness of the triceps (TSF),
      and arm muscle circumference (AMC). Using the BIA-106, RJL System, the
      bioelectrical resistance, bioelectrical reactance and phase angle were measured.
      Correlation analysis revealed a significant correlation between gender,
      anthropometry and bioelectrical resistance. A significant correlation between
      age, anthropometry and reactance was also noted. Both male and female subjects in
      the fourth quartile of the age distribution showed significantly lower reactance
      and phase angle. The quartile study of the body mass index revealed corresponding
      changes in weight, BMI, TSF, AMC and resistance in quartiles, but not reactance.
      In conclusion, in addition to anthropometry, gender has an effect on
      bioelectrical resistance, and age has an effect on reactance.

PMID- 1363633
TI  - Occupational exposure and respiratory morbidity among asbestos workers in Taiwan.
AB  - To determine the prevalence of asbestos-related lung disease and the impairment
      of lung function among asbestos workers, we conducted a cross-sectional health
      survey of 459 workers in 33 asbestos-related factories in Taiwan. Each worker was
      asked about his medical and occupational history and was given a medical
      examination, chest roentgenogram and pulmonary function test. Manufacturing
      processes included production of asbestos cements, textiles, friction materials
      and insulation products. Exposure assessments were based on asbestos sampling and
      counting using a phase contrast microscope. The average age of the participants
      in the study was 41.6 years. They had an average of 8.1 years of dust exposure,
      with a range of one to 42 years. The majority had a cumulative asbestos exposure
      of less than 20 fiber years/mL. No case of asbestos-related lung disease was
      found during our investigation. No roentgenogram showed unequivocal changes of
      asbestosis. However, a multiple linear regression analysis of the pulmonary
      function test showed that both FVC and FEV1 decreased significantly with an
      increasing cumulative dose of exposure after controlling for age, height and
      smoking effects during analysis. FEV1/FVC and FEF25-75% were not affected by
      exposure dose. The absence of asbestosis and other asbestos-related lung diseases
      may be due to an inadequate induction time of asbestos exposure and a possible
      healthy selection of workers. We conclude that among workers in Taiwan, there is
      a significant effect on the respiratory system, especially pulmonary function,
      due to asbestos exposure.

PMID- 1363635
TI  - Mortality trends of pancreatic cancer: an affluent type of cancer in Taiwan.
AB  - Interest in the increasing trends in pancreatic cancer mortality in Taiwan has
      recently emerged. The mortality data for pancreatic cancer in Taiwan from 1971 to
      1988 for both sexes are presented to cast some light on the etiology of this
      ominous and yet little-known disease. A steeply increasing trend was found
      between 1975 and 1984 for both sexes; it dropped in 1985-86 and climbed again in
      1987-88. The urban excess risks persisted in our study period of 18 years.
      Further study is mandatory to elucidate the etiological implications of dietary
      and other lifestyle changes on the magnitude of these rising secular trends and
      urban-rural gradients, particularly in the elderly, as well as the puzzling
      finding of cross-sectional drops in mortalities between 1985 and 1986. It is
      speculated that the drop may be associated with an economic recession that
      occurred in Taiwan between 1980 and 1981.

PMID- 1363636
TI  - Surgical management of Graves' ophthalmopathy: stage I, inferomedial orbital
      decompression.
AB  - Inferomedial orbital decompression was done on 26 eyes with dysthyroid optic
      neuropathy (DON), seven eyes with corneal exposure which had not responded to
      topical lubricants, and six with disfiguring exophthalmos. Twenty-one of the 26
      DON eyes (80.7%) had visual acuity improvement equal to or greater than two lines
      by the Snellen chart, and there was only one in all 39 eyes that dropped more
      than two lines. The average retinal sensitivity improvement was of borderline
      significance (4.25 +/- 5.73 dB), but for those 13 severely affected eyes
      (preoperative sensitivity loss > or = 10 dB), 11 (84.6%) of them showed
      significant improvement. There were 16 bilateral and seven unilateral cases. Out
      of all 39 eyes, the average retroplacement effect was 4.6 +/- 2.3 mm, and none of
      them had postoperative asymmetry greater than 2 mm by Hertel's exophthalmometry.
      Although the palpebral fissure height tends to remain the same after surgery,
      upper lid retraction is likely to be worse. The most frequent sequela was
      diplopia, which tended to occur in more severely myopathic eyes regardless of the
      surgical approach used. Although a staged approach is mandatory in surgical
      treatment of this disorder, individualization of surgical goals and
      intraoperative titration of the retroplacement effect are of equal importance for
      optimal results.

PMID- 1363637
TI  - Chromosomal screening of mentally retarded school children in Taipei.
AB  - The major concern of the national population policy in Taiwan in recent years has
      been to lower the incidence of hereditary diseases and mental retardation in the
      general population. It has been estimated that there are around 10,000 mentally
      retarded school children in Taiwan. If effective chromosomal screening can be
      extended to these children, some of the family members who are carriers of
      balanced chromosomal rearrangements may benefit from follow-up studies and
      genetic counseling. The present report is the result of a pilot study conducted
      from 1988 to 1991 to explore the possibility of chromosomal screening of mentally
      retarded school children in Taipei. A total of 871 blood samples were collected
      from 1,147 children registered in 46 schools or residing in homes for the
      retarded. Chromosomal analysis was successfully accomplished on 674 out of 871
      blood samples. The following chromosomal abnormalities were observed: 28 Down's
      syndrome, four Klinefelter syndrome, one XYY, one triple X, 11 translocations,
      seven inversions, four mosaics, three duplications, one deletion and one with an
      extra marker chromosome. After follow-up cytogenetic analyses of 13 families with
      probands with structural chromosomal anomalies, three of these families were
      shown to have one or two carriers of balanced translocated chromosomes. It seems
      that the present screening system would not be practical or cost-effective if it
      were applied island-wide in the future.

PMID- 1363638
TI  - Experimentally induced axial dysraphism and anorectal malformation in male rat
      fetuses by intragastric administration of ethylenethiourea.
AB  - Pregnant Sprague Dawley rats were separated into two groups. In the experimental
      group, single intragastric doses of ethylenethiourea (ETU) were given on the 11th
      day of gestation. In the control group, a single intragastric dose of distilled
      water was given on the same day of gestation. Fetuses were recovered on day 20 of
      gestation, and were prepared for dissection and light microscopy. A high
      incidence of axial dysraphic disorders (omphalocele and rachischisis) and
      imperforate anus with recto-urethral fistula were noted in experimental male rat
      fetuses obtained from dams subjected to varying doses of ETU.

PMID- 1363640
TI  - Effect of food on pharmacokinetics of cefuroxime axetil in Chinese subjects.
AB  - The effect of food on the pharmacokinetics of cefuroxime axetil was studied.
      Twelve healthy male subjects were included in this study. They were given single
      oral 500 mg doses of cefuroxime axetil alone or with food based on a balanced two
      way crossover design. Plasma cefuroxime concentrations were assayed by the high
      performance liquid chromatographic method. When the drug was given alone, the
      area under the curve (AUC) was 15.77 +/- 4.12 mg*h/L, Cmax was 4.20 +/- 1.05
      mg/L, Tmax was 2.36 +/- 0.84 h, T1/2 was 1.56 +/- 0.26 h, and Clp/F was 34.13 +/-
      10.39 L/h; 45.12 +/- 9.59% of the dose was recovered in the urine within 24
      hours, and the renal clearance was 12.58 +/- 4.41 L/h. When the drug was given
      with food, the corresponding AUC was 23.46 +/- 4.57 mg*h/L, Cmax was 7.10 +/-
      1.41 mg/L, Tmax was 2.04 +/- 1.32 h, T1/2 was 1.40 +/- 0.23 h, and Clp/F was
      21.93 +/- 5.18 L/h; the 24-hour urinary recovery was 69.33 +/- 6.13% and the
      renal clearance was 12.58 +/- 2.99 L/h. The above pharmacokinetic parameters
      obtained from the two regimens were compared by two-way ANOVA corrected for the
      change-over effect. No significant difference was found for Tmax, T1/2 or renal
      clearance (p > 0.05). Higher AUC, Cmax, urinary recovery and lower Clp/F values
      were observed for the regimen with food (p < 0.05). The plasma drug
      concentrations resulting from the regimen with food were higher throughout the 12
      hour sampling period when compared to the regimen without food.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1363639
TI  - Xanthomonas maltophilia bacteremia: an analysis of 32 cases.
AB  - Thirty-two cases of Xanthomonas maltophilia bacteremia have been identified over
      the last two years at the Veterans General Hospital, Taipei. Among them, 27 cases
      (84%) were due to hospital-acquired infections, and 14 cases (44%) were
      polymicrobial bacteremia. One case was confirmed as prosthetic valve endocarditis
      and one case was complicated by recurrent attacks of ecthyma gangrenosum. Most
      cases had severe debilitating conditions. Twelve cases (38%) had a malignancy, 19
      cases (59%) were resident in the Intensive Care Unit and 16 cases (50%) had
      undergone major surgery. The main predisposing factors included central venous
      catheterization, endotracheal intubation or tracheostomy, prior antibiotic
      therapy and prolonged hospitalization. Moxalactam, chloramphenicol and
      trimethoprim-sulfamethoxazole were the most effective agents in vitro against X.
      maltophilia. Twenty-two cases (69%) died during hospitalization; 13 cases (41%)
      were directly attributed to septicemia. Factors that adversely influenced
      mortality included inappropriate antimicrobial therapy and prior antibiotic
      treatment. Of particular interest is the fact that none of the patients who did
      not receive appropriate antimicrobial therapy survived. Early diagnosis and
      appropriate antibiotic therapy are critical for improving the prognosis of X.
      maltophilia infection.

PMID- 1363641
TI  - The role of endothelin-1 during ischemia-reperfusion injury.
AB  - In order to investigate the role of endothelin-1 during ischemia-reperfusion
      injury, 80 adult male Wistar rats were subjected to three hours of ischemia and
      one hour of reperfusion. Animals were evenly divided into eight groups. The rats
      in group 1 served as the normal control group, while the rats in group 2 received
      an intravenous infusion of endothelin-1 in a dosage of 0.5 ng/kg/min, group 3 in
      a dosage of 5 ng/kg/min, and group 4 in a dosage of 50 ng/kg/min. The rats in
      group 5 were infused with angiotensin II (10 ng/kg/min). The rats in group 6
      received an intravenous infusion of 10,000 units of superoxide dismutase and
      10,000 units of catalase. Group 7 rats were infused with endothelin-1 (50
      ng/kg/min), superoxide dismutase (10,000 units), and catalase (10,000 units).
      Group 8 rats received an infusion of angiotensin II (10 ng/kg/min), superoxide
      dismutase (10,000 units) and catalase (10,000 units). The infusions were given
      during the reperfusion period. After one hour of reperfusion, the gastrocnemius
      and soleus muscles of the experimental animals were excised and assayed for
      ischemia-reperfusion injury by measuring triphenyltetrazolium chloride (TTC)
      reduction. The results showed that the limb activity of the ischemic extremity
      was 40.33 +/- 2.75% in group 1, 41.62 +/- 4.08% in group 2, 14.42 +/- 3.14% in
      group 3, 4.43 +/- 1.05% in group 4, 23.81 +/- 3.51% in group 5, 57.23 +/- 4.52%
      in group 6, 31.79 42- 3.63% in group 7, and 27.39 +/- 3.95% in group 8.
      Endothelin-1 reduced the limb activity in a dose-dependent manner.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1363642
TI  - Cerebrotendinous xanthomatosis in three siblings from a Taiwanese family.
AB  - We present and discuss the clinical and biochemical findings of three siblings
      with cerebrotendinous xanthomatosis, which has not been previously reported in
      Taiwan. Clinical features consisted of tendinous xanthomas, cataracts, mental
      defects, pyramidal signs, cerebellar ataxia, peripheral neuropathy and renal
      stones. Biochemical findings included normal serum cholesterol levels, high serum
      cholestanol levels and elevated serum cholestanol to cholesterol ratios. The
      serum levels of cholesterol precursor (lathosterol) and plant sterols
      (campesterol, sitosterol) were also elevated.

PMID- 1363643
TI  - Hypothalamic amenorrhea in a case of mitochondrial encephalomyopathy.
AB  - A 26-year-old female with myoclonus epilepsy associated with ragged-red fibers is
      reported. Clinically, she had myoclonus epilepsy, cerebellar ataxia, a bilateral
      neurosensory type hearing loss, retinitis pigmentosa and short stature. She also
      presented with primary amenorrhea and poor development of secondary sexual
      characteristics. Endocrinologic studies revealed that hypothalamic dysfunction
      was the most plausible cause of her primary amenorrhea. Magnetic resonance
      imaging showed marked dilatation of the third ventricle indicating thalamic and
      hypothalamic degeneration. We conclude that hypothalamic dysfunction may be one
      of the characteristic features of mitochondrial encephalomyopathies.

PMID- 1363644
TI  - Extrathoracic sarcoidosis in a Chinese man presenting with multiple, large
      plaques and tumors.
AB  - We report an unusual case of tumorous sarcoidosis in a 42-year-old Chinese man
      with extrathoracic sarcoidosis. He presented with multiple large plaques and
      tumors on the neck and extremities of a nine-year duration. Because of the
      atypicality of the cutaneous manifestation, the lack of intrathoracic lesions and
      the rarity of sarcoidosis in Taiwan, the case remained undiagnosed for nine years
      despite numerous examinations and tests. A subsequent skin biopsy revealed
      sarcoidal granulomas. The detection of cytoplasmic birefringent inclusions in the
      granulomas led to the final diagnosis. Originally thought to be foreign bodies,
      the inclusions were proven to be calcium oxalate by x-ray microanalysis and
      calcium oxalate stain. Lymph node and liver biopsies confirmed the diagnosis. The
      skin lesions in this case may have been precipitated by frequent harsh scrubbing
      to clean the skin. Sarcoidosis should be considered in the differential diagnosis
      in patients presenting with multiple cutaneous tumors. This case also illustrates
      that detection of calcium oxalate inclusions in granulomas, while not specific,
      can serve as a valuable clue in the diagnosis of cutaneous sarcoidosis.

PMID- 1363645
TI  - Magnetic resonance imaging of Ebstein's anomaly: report of two cases.
AB  - Among 388 cases of congenital heart disease with magnetic resonance imaging (MRI)
      from September 1990 to February 1992, we came across two cases of Ebstein's
      anomaly. They had been previously diagnosed as Ebstein's anomaly by
      echocardiography and cinecardioangiography. The first case was a three-year-old
      boy with complex congenital heart disease that included Ebstein's anomaly, a
      double-outlet right ventricle, pulmonary hypertension, tricuspid regurgitation,
      mitral regurgitation, a ventricular septal defect and an atrial septal defect.
      The second was a 13-year-old boy who also had Ebstein's anomaly, but had received
      a tricuspid valve replacement at the age of five. In Ebstein's anomaly, we found
      that MRI offers exquisite endocardial and epicardial details. We anticipate that
      in the future MRI will help to eliminate invasive studies.

PMID- 1363646
TI  - Monitoring of serum neopterin in renal transplant recipients.
AB  - Postoperative management of kidney allograft recipients requires a reliable and
      rapid diagnostic method so that proper therapy can be initiated. In this study,
      we tried to correlate serum neopterin levels with different conditions after
      transplantation. Serial serum neopterin levels were assessed after operation.
      Serum neopterin levels of uremic patients were significantly higher than those of
      healthy persons (239.9 +/- 177.7 nmole/L, n = 33 vs 6.14 +/- 2.78 nmole/L, n =
      10, p < 0.001). In recipients with a stable post-transplant course, the serum
      neopterin level was low. On the contrary, acute rejection episodes were
      associated with a high level of serum neopterin which declined after successful
      treatment, although the difference was not significant (96.2 +/- 57.7 nmole/L vs
      56 +/- 38.1 nmole/L, p > 0.05). The serum neopterin level was also high in post
      transplant acute tubular necrosis (ATN, 256.6 nmole/L), which gradually declined
      parallel to the resolution of ATN. The neopterin level was low in patients with
      cyclosporine nephrotoxicity (17.8 +/- 7.6 nmole/L). In summary, the serum
      neopterin levels were persistently high in uremic and post-transplant ATN
      patients. Acute rejection episodes were correlated with an increased level of
      neopterin. It appears that daily measurement of the serum neopterin level may be
      useful for biochemical detection of immunologic complications in allograft
      recipients.

PMID- 1363647
TI  - Neonatal screening for alpha-thalassemia in southern Taiwan.
AB  - Screening peripheral or cord blood from newborn infants has been used for early
      detection of alpha-thalassemia conditions. The level of hemoglobin Bart's (Hb
      Bart's) in the blood correlates with the degree of alpha-gene deletion. Hence,
      the degree of gene deletion in an alpha-thalassemia carrier state can be
      estimated. Two thousand cord blood samples collected from the Tainan area were
      screened with cellulose acetate membrane electrophoresis for Hb Bart's. Ninety
      nine of the 2,000 samples (4.95%) were positive for Hb Bart's. Concentrations of
      Hb Bart's varied from 3.2% to 30.7%. Of the 99 cases with Hb Bart's, 22 had Hb
      Bart's levels of 3.0% to 9.9%; 54 had Hb Bart's levels of 10.0% to 19.9%; and 23
      had Hb Bart's levels of 20% to 40%. Routine cord blood screening by hemoglobin
      electrophoresis is recommended.

PMID- 1363648
TI  - Hemiparkinsonism in a patient with frontal meningioma.
AB  - We report on a 44-year-old woman with a right frontal meningioma, who presented
      with resting tremor, rigidity and bradykinesia in the left limbs. There were no
      other neurologic manifestations. A computed tomography scan demonstrated a huge
      high-density mass in the right frontal lobe and marked surrounding edema causing
      compression of the basal ganglia. Cerebral angiography showed a typical sunburst
      tumor stain and three feeding vessels from the bilateral middle meningeal
      arteries and the right callosomarginal artery. The pathologic diagnosis was
      transitional type meningioma. Before surgery, treatment with levodopa and
      bromocriptine was significantly effective in controlling hemiparkinsonism, which
      completely disappeared after surgical removal of the tumor. This outcome supports
      the notion that local compression due to edema may cause a functional disorder in
      the basal ganglia producing reversible contralateral parkinsonism.

PMID- 1363649
TI  - Clonal analysis of agnogenic myeloid metaplasia.
AB  - Agnogenic myeloid metaplasia (AMM) is a chronic myeloproliferative disorder that
      leads to a sustained proliferation of megakaryocytes and an increase of reticulin
      fibers within the bone marrow. Blood and bone marrow samples from patients with
      advanced AMM with fully developed myelofibrosis as well as cases in the cellular
      phase of the disease were investigated for clonality. Clonality was studied by X
      linked restriction length polymorphism in conjunction with DNA methylation
      patterns. Granulocytes and total bone marrow cells proved to be monoclonal in
      origin whereas at least a minor portion of the peripheral lymphocytes were not
      clonally derived. Our findings indicate that the cellular phase of AMM as well as
      the fully developed disease progressed to myelofibrosis represent a monoclonal
      proliferation of pluripotent hematopoietic stem cells.

PMID- 1363651
TI  - Proceedings of the International Glaucoma Symposium. Brussels, May 24, 1992.

PMID- 1363652
TI  - Recent developments in medical therapy of POAG with beta blocking agents.
AB  - Since 1987, an entirely computerized open study has been developed in Pr Sole's
      Ophthalmology Department: the CLERTORE project (Clermont-Tonus-Research). It is a
      data bank including all the ophthalmic data of hypertensive patients, whether
      treated or untreated. Every six months, the patients included in the CLERTORE
      project undergo a clinical ophthalmic examination as well as an automated visual
      field examination (OCTOPUS 500), an examination of the optic disc (ONHA) and
      fluorophotometry (FLUOROTRON MASTER). To date, 92 patients have been included in
      the project. One hundred and eighty-three eyes are examined every six months with
      a maximal follow-up of 42 months. Because of the numerous criteria of the data
      base, it is too early to give any statistical results. With a close look at the
      evolution of the examinations of some of our cases, this preliminary work however
      allows us to make the three following remarks: In the hypertensive patients, a
      modification of the papillary pallor is observed without any change in the visual
      field, C/D ratio and fluorophotometry. The pallor is clearly modified when
      adrenaline eye drops are given to glaucomatous patients. There is a break of the
      iridic blood barrier in some hypertensive patients, whether treated or untreated.

PMID- 1363653
TI  - Longitudinal follow up of glaucoma suspects tested with pattern
      electroretinogram.

PMID- 1363650
TI  - [The central neurophysiological and neurochemical mechanisms of vomiting (a
      review of the literature)].
AB  - The review contains the present-day evidence on neurophysiological and
      neurochemical mechanisms of functioning the central components of vomiting
      reflex. The main attention is concentrated on the role of some brain structures
      in motion sickness-induced vomiting. At the same time, the literature data
      casting doubt on traditional view of a necessary involvement of some brain
      structures in the genesis of vomiting induced by motion sickness are discussed.
      Also there are findings of studying an effect of physiologically active
      substances (classical neuromediators and regulatory peptides) at a neuronal level
      (silent postremal cells) with the presence of an emetic effect in them during
      systemic administration. The current concept of vomiting center to which role the
      parvicellular reticular formation of brain stem can pretend is under study.

PMID- 1363654
TI  - [Immunocytochemical research on mediators of centrifugal visual neurons in
      lampreys (Lampetra fluviatilis)].
AB  - The aim of this study has been to investigate different neuroactive substances in
      the lamprey centrifugal visual neurons (CVN) by combining axonal tracing methods
      and immunocytochemistry. The CVN somata are immunonegative to antibodies
      recognizing FMRF-amide, LH-RH, 5 HT and TH, but immunopositive to an anti-GABA
      antiserum (GABA+) in a proportion of 40%. In the retina, the GABA+ axon terminals
      mainly synapse upon GABA+ and GABA- amacrine cell bodies and dendrites, and on
      dendrites of GABA- ganglion cells.

PMID- 1363655
TI  - Modern Trends in Orthopaedic Surgery and Pathology. Proceedings. Bologna, Italy,
      11-13 April 1991.

PMID- 1363656
TI  - [Sleep induction].
AB  - Physiological sleep induction is a fragile phenomenon which may be altered by
      environmental factors and various somatic and psychiatric disorders. Therefore
      sleep induction disorder is a common component of different types of insomnia,
      including sleep-onset insomnia and to a lesser degree multiple awakenings
      insomnia and early morning awakening insomnia. The treatment of sleep induction
      disorders is difficult and requires a precise analysis of the disorder and its
      aetiological factors. Specific treatment of aetiological factors is more likely
      to be efficacious in the long term than pharmacological sleep induction (eg:
      psychiatric disorders, sleep apnea syndrome, restless leg syndrome, periodic
      movements in sleep, disorders of the sleep-wake schedule...) when the use of
      hypnotic drugs is necessary agents not altering sleep architecture are preferred.
      Non-pharmacological methods could be used to induce sleep because they provide a
      better long term efficacy: sleep hygiene, relaxation techniques, biofeedback
      technique, psychotherapeutic techniques. Recently, some authors stress the use of
      treatment by restriction of time in bed and stimulus control treatment.

PMID- 1363657
TI  - [Contribution of zolpidem in the management of sleep disorders].
AB  - Zolpidem is a nonbenzodiazepine hypnotic agent belonging to a new class of
      psychotropic drugs the imidazopyridines which enhance the GABAA receptor function
      by interacting with a specific receptor population. Zolpidem binds selectively to
      the Omega-1 receptor subtype and from a pharmacological point of view differs
      from benzodiazepines (BZD) by producing a strong sedative and hypnotic profile
      which predominates over the anticonvulsivant and anxiolytic activity and moreover
      appears practically devoid of myorelaxant properties. From a pharmacodynamic
      point of view, these results suggest that zolpidem facilitates more selectively
      than BZD, GABAA function and produces a selective hypnotic effect. Though if the
      role played by receptors in tolerance and dependence has not been yet fully
      elucidated, it could be described as an adaptative process to sustained
      stimulation of GABA function. Animal data obtained with zolpidem differs
      substantially from that of the BZD and indicates that repeated zolpidem
      administration may not lead to phenomena of tolerance and withdrawal syndrome
      after abrupt drug discontinuation. In human following oral intake, zolpidem is
      very rapidly (Tmax: 30-40 min) absorbed. The clearance is essentially metabolic
      and less than 1% is recovered in urine. The apparent plasma half-life is of 2.0
      2.5 hours in most adult subjects and metabolites are totally inactive. The
      hypnotic activity of zolpidem and its effects on sleep architecture have been
      assessed in polysomnographic studies: 11 studies in 579 healthy volunteers and 12
      studies in 202 insomniac patients. From all the patient studies, it emerges
      clearly that zolpidem at the dose of 10 mg significantly decreases sleep onset
      latency, the number and the duration of nocturnal awakenings, and concomitantly
      increases total sleep time. Furthermore, at variance with what observed with
      reference benzodiazepine hypnotics, zolpidem does not alter patient sleep
      architecture: it increases only moderately stage 2, it increases, when reduced,
      stages 3 and 4 (slow wave sleep) and it does not decrease REM sleep. Clinical
      studies conducted on more than 4,000 insomniac patients have clearly shown that
      at the dose of 10-20 mg, zolpidem induces from the first night a definite
      hypnotic effect in all types of insomnia. In elderly subjects an initial dose of
      5 mg should be considered. The possible presence of residual effects during the
      day following administration of zolpidem has been assessed in 535 healthy
      volunteers and in 133 insomniac patients according to a double blind (versus
      placebo and/or benzodiazepine) controlled design.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1363659
TI  - [Neurotransmitters, neuropeptides and eating behavior].
AB  - A number of monoamines and neuropeptides are involved in the control of eating
      behavior. In the central nervous system, the medial and lateral hypothalamus
      (connected with cortical and limbic systems as well as with the peripheral
      endocrine and autonomic nervous systems) integrates informations concerning the
      nutritional and biopsychological status and control feeding behavior and weight
      regulation. Modern neurobiological techniques have generated a great range of
      information on the role of monoamines and neuropeptides in controlling food
      intake. Substances such as norepinephrine, opioids, neuropeptide Y are potent
      stimulators of investive behavior. Serotonin, cholecystokinin, and corticotropin
      releasing factor inhibit food intake. The physiological influence of these
      substances is undergoing evaluation.

PMID- 1363660
TI  - Comparative cardiac haemodynamics of bisoprolol, celiprolol, carvedilol and
      nebivolol in normal volunteers.
AB  - Nebivolol is a novel selective beta 1-adrenergic antagonist with an unusual
      haemodynamic profile. It improves left ventricular function in normals and in
      patients with a damaged left ventricle. We compared the cardiac effects of a 14
      day treatment period with 10 mg o.d. of bisoprolol, 400 mg o.d. of celiprolol, 25
      mg o.d. of carvedilol and 5 mg o.d. of nebivolol in a placebo-controlled
      crossover study in 7 volunteers with a mean age of 39 (range 30-53) years.
      Cardiac haemodynamics were assessed serially by means of systolic time intervals.
      The ratio of the preejection period to the left ventricular ejection time
      (PEP/LVET) was used as a indirect measure of left ventricular performance. The
      results show that the PEP/LVET is a very sensitive and reproducible index of left
      ventricular function. During treatment with placebo and bisoprolol no changes
      occurred; during treatment with celiprolol and carvedilol a significant but
      transient decrease of PEP/LVET occurred, and only during treatment with nebivolol
      a long-lasting and significant decrease of PEP/LVET occurred. With bisoprolol an
      increase of PEP and QS2c (total electromechanical systole) was observed,
      indicative of a negative inotropic effect. In conclusion, nebivolol, in contrast
      with both classical and vasodilating beta-blocking agents, substantially improves
      left ventricular function, possibly due to an improvement of diastolic function
      and left ventricular compliance, which may be of therapeutical value in the
      treatment of congestive heart failure.

PMID- 1363658
TI  - Pharmacological properties and mechanism of action of the cyclopyrrolones.
AB  - We present the pharmacological properties of two cyclopyrrolones, zopiclone as a
      hypnotic and suriclone as an anxiolytic, and examine their mechanism of action.
      The effects of zopiclone on the amount of time spent at each vigilance level have
      been studied in freely moving rats. Zopiclone from 2.5 mg/kg i.p. extends the
      duration of slow wave sleep (SWS), concomitantly shortening the periods awake.
      This SWS inducing effect of zopiclone was more potent after 10 mg/kg i.p.;
      moreover, zopiclone did not depress REM sleep and no rebound of activity in
      wakefulness or REM sleep were observed the day after zopiclone treatment. In
      rats, at the cortical level, zopiclone increases the spectral energy in the delta
      band (0.5 to 4 hertz). This rise in energy appears at doses starting from 1.25
      mg/kg p.o. and can also reach the fast frequencies (beta band: 12 to 16 hertz).
      This power spectrum is characteristic of a compound having tranquilizing-hypnotic
      potential. Taken together these EEG results corroborate the clinical studies. In
      man, zopiclone increased SWS, decreased SWS latency and respected sleep
      architecture in both healthy volunteers and insomniacs. This respect of sleep
      structure and the relative short duration of action of zopiclone minimized the
      residual effects seen upon waking (drowsiness, impairment of psychomotor
      performance). In the Geller-Seifter test, an operant conflict procedure, the
      minimal effective dose (MED) of suriclone in reversing the conflict-induced
      inhibition of drinking behavior was 2.5 mg.kg-1 p.o. in rats. Depression of
      unpunished responding is only seen at higher doses (20 mg.kg-1 p.o.).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1363661
TI  - Transcriptional regulation in cell differentiation and development. Proceedings
      of the joint British Society for Cell Biology -- Company of Biologists Symposium.
      Brighton, April 1992.

PMID- 1363663
TI  - Pax genes, mutants and molecular function.
AB  - The paired domain is a conserved DNA binding motif which was first found in
      Drosophila segmentation gene products. This paired domain is encoded by a well
      conserved, paired box DNA sequence, also detected in the genomes of other
      species. The mouse paired box-containing genes are referred to as Pax genes and
      are expressed in a distinct spatiotemporal pattern during embryogenesis. Pax
      proteins are able to bind to specific DNA sequences and modulate transcriptional
      activity. Interestingly, three different Pax genes have already been shown to
      correspond to some mouse and human mutants, emphasizing their role as
      developmental control genes.

PMID- 1363662
TI  - Targets of homeotic gene regulation in Drosophila.
AB  - We have used a chromatin immunopurification approach to identify target genes
      regulated by the homeotic gene Ultrabithorax. A monoclonal antibody against the
      Ultrabithorax gene product is used to immunopurify in vivo Ultrabithorax protein
      binding sites in embryonic chromatin. The procedure gives an enrichment of
      sequences with matches to a consensus homeodomain binding site. In one case we
      have shown that an immunopurified sequence lies within a 4 kb fragment that acts
      in vivo as a homeotic response element. We anticipate that this approach will
      enable us to identify further targets, allowing the analysis of their regulation
      and function. The chromatin immunopurification strategy may be of general
      application for the identification of direct in vivo targets of DNA-binding
      proteins.

PMID- 1363665
TI  - Research and Applications in Computerized Electrocardiology. Proceedings of the
      17th Annual ISCE Conference. Keystone, Colorado, May 2-7, 1992.

PMID- 1363664
TI  - [Chronic prostatodynia and psychosomatic care].
AB  - Depression is a regular accompaniment of all chronic painful conditions. A study
      was conducted to assess the effect of treatment of the depressive factor in
      patients with chronic prostatodynia. Effects were compared of psychosomatic
      therapy (psychotherapy, relaxation, etc.) alone in 9 patients (group I) and the
      same psychosomatic care plus treatment with amineptine and clobazam in 9 patients
      (group II). Results showed that 2 patients recovered and 3 were improved (62%)
      with 1 drop-out in group II, versus recovery and 2 improvements (42%) with 2 drop
      outs in group I. These findings are analyzed and discussed.

PMID- 1363666
TI  - Proceedings of the 1st International Congress on Vitamins and Biofactors in Life
      Science. Kobe, Japan, September 16-20, 1991.

PMID- 1363667
TI  - Morphogenetic roles of retinoic acid.
AB  - We integrated our information on morphogenetic roles of retinoic acid, focusing
      on development of chick limb. Retinoic acid has been considered to be a putative
      morphogen released from the ZPA. However, since exogenous retinoic acid induces
      expression of RAR beta, but not grafted ZPA, the ZPA is unlikely to produce
      retinoic acid. From the result that retinoic acid-treated cells induce digit
      duplication, retinoic acid converts anterior cells into ZPA cells. We found that
      retinoic acid also induces expression of homeobox genes indirectly and that bFGF
      enhances expression of the homeobox genes. Thus, we considered that retinoic acid
      and growth factors cooperate with each other to activate homeobox genes. A
      morphogenetic role of retinoic acid is to coordinate developmental stage of each
      cells by controlling expression of homeobox genes.

PMID- 1363668
TI  - Neurotransmitter releasing action of 6R-tetrahydrobiopterin.
AB  - We showed that 6R-BH4, a natural cofactor for aromatic amino acids hydroxylases,
      can stimulate exocytotic DA release independently of its cofactor activity, and
      ACh release via monoaminergic system. From these results, it is quite likely that
      6R-BH4 plays an important role in the regulation of neuronal activity, as a
      modulator of neurotransmitter release as well as a cofactor for hydroxylases.

PMID- 1363670
TI  - Effects of stimulation of the dorsal motor nucleus of the vagus on the
      extrahepatic biliary system in dogs.
AB  - This study was performed to determine the distribution of excitatory and
      inhibitory areas in the dorsal motor nucleus of the vagus (DMV) for the
      gallbladder and sphincter of Oddi in spinal cord-transected dogs. Microinjection
      of 0.5 M L-glutamate into the DMV induced various effects on the gallbladder and
      sphincter of Oddi. Stimulation at the rostral portion of the DMV elicited only
      excitatory effects on both motilities. Stimulation at the middle portion of the
      DMV induced excitatory, inhibitory, or combined effects on the gallbladder and
      excitatory or combined effects on the sphincter of Oddi. Stimulation at the
      caudal portion of the DMV elicited the three different effects on the sphincter,
      but only relaxation of the gallbladder. The locations of the excitatory and
      inhibitory points for the gallbladder and sphincter were mixed in the DMV at the
      levels near the obex. From these results, it was concluded that the inhibitory
      points for the gallbladder and sphincter of Oddi are distributed in the caudal
      portion of the DMV, while their excitatory points are distributed over a wide
      area and in the more rostral portion of the DMV.

PMID- 1363671
TI  - [Hypertensive heart. Experience in the clinical use of sectral (acebutolol)].

PMID- 1363672
TI  - [The third generation of b-blockers: new possibilities ].

PMID- 1363669
TI  - The actions of baclofen on neurones and synaptic transmission in the nucleus
      tractus solitarii of the rat in vitro.
AB  - 1. Intracellular and whole-cell patch recordings were made from sixty-seven
      neurones located in the nucleus tractus solitarii (NTS) in transverse slices of
      rat brainstem. 2. Baclofen at concentrations of 2-20 microM caused
      hyperpolarization from normal resting membrane potentials (Vm). This response was
      associated with a decrease in input resistance (Rm) tested by current pulses in
      discontinuous current clamp mode when membrane potential was restored to control
      level by current injection. In single electrode discontinuous voltage clamp mode,
      baclofen at these concentrations caused a small (< 50 pA) outward current
      associated with increased membrane conductance measured by voltage steps from
      holding potentials (Vh) of -50 or -60 mV. Current-voltage relations at these Vhs
      and the results of varying Vh between -50 and -110 mV during responses to
      baclofen gave a reversal potential of -73 mV. The amplitudes of baclofen
      responses were related to K+ concentration tested by comparing responses in media
      containing 1-24 mM extracellular K+, indicating that postsynaptically baclofen
      acts via a K+ conductance. 3. These effects were still apparent in the presence
      of tetrodotoxin (which did not abolish all spontaneous synaptic activity) and
      also in medium containing a combination of Co2+, the excitatory amino acid
      antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and the GABAA antagonist
      bicuculline which blocked synaptic activity. 4. The amplitude and frequency of
      spontaneous postsynaptic potentials (spPSPs) and spontaneous postsynaptic
      currents (spPSCs) were reduced by baclofen at concentrations (1 microM or less)
      which had no effect on membrane potential or holding current in current or
      voltage clamp recordings respectively. 5. The amplitude of evoked excitatory
      (evEPSPs/evEPSCs) and inhibitory (evIPSPs/evIPSCs) synaptic events elicited by
      electrical stimulation in the vicinity of the tractus solitarius (TS) was reduced
      by low concentrations of baclofen (250 nM-1 microM) which did not produce
      discernible postsynaptic responses. 6. In order to examine the effects of
      baclofen on excitatory synaptic events without contamination with inhibitory
      events, stimulation of the TS was carried out in the presence of bicuculline.
      Conversely to investigate actions on purely inhibitory synaptic responses
      experiments were carried out with CNQX in the bathing solution. Inhibitory
      synaptic responses could still be evoked, presumably by stimulation of
      interneurones in the vicinity of the TS. IPSPs/IPSCs were more sensitive to
      baclofen than EPSPs/EPSCs. 7. The effects of baclofen on membrane potential or
      holding current and PSP/PSCs were antagonized by 2-hydroxysaclofen (400 microM)
      confirming that baclofen was acting at gamma-aminobutyric acid (GABA)B
      receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1363673
TI  - Neuronal changes in the nigrostriatal pathway of 1-methyl-4-phenylpyridine
      treated mice.
AB  - Thirty young-adult mice were treated with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) 30 mg/kg/day for 2 days and sacrificed 24 hours later
      in order to determine striatal catecholamines and to study morphological changes
      in the nigrostriatal pathway. Immunohistological techniques were also used with
      polyclonal antibodies for glial fibrillary acidic protein (GFAP) and tyrosine
      hydroxylase (TH), and monoclonal antibodies for two subunits of neurofilaments.
      Silver impregnation demonstrated conspicuous neuronal changes affecting cellular
      processes from substantia nigra in all treated mice. Terminal and axonal
      degeneration were also observed in striata. These changes were associated with a
      moderate to marked gliosis. The TH immunoreactivity was normal in cell bodies of
      substantia nigra but was decreased in striata from MPTP-treated mice. These data
      indicate that in mice the deterioration of dendritic and axonal neuropil may
      constitute a significant causal factor of MPTP neurotoxicity.

PMID- 1363674
TI  - [Neuroleptic malignant syndrome and related conditions].
AB  - Neuroleptic malignant syndrome is characterised by muscular rigidity, fever and
      signs of severe vegetative nervous system involvement. Its etiopathogenesis is
      still unclear and the disease is potentially fatal. Its clinical aspects, which
      are often only partially manifested, make it difficult to formulate a correct
      diagnosis in time, not least due to the problem of differential diagnosis with
      other syndromes with similar symptoms but a different pathogenesis,
      psychopathology and therapy: acute lethal catatonia, fatal acute delirium, heat
      stroke, malignant hyperthermia. The speed of the diagnosis is vital for effective
      therapy, but this is made even more difficult by the need approach. The paper
      presents eleven case studies; after an analysis of the numerous clinical aspects
      of the syndrome and the definition of its diagnostic parameters, an appropriate
      therapeutic protocol is outlined. Lastly, the problem of retreatment using a
      neuroleptic of the same or a different class is discussed once the acute phase
      has been overcome.

PMID- 1363676
TI  - Analysis of the regions responsible for IS6110 RFLP in a single Mycobacterium
      tuberculosis strain.
AB  - A high degree of IS6110 restriction fragment length polymorphism (RFLP) is
      observed amongst the different strains of the Mycobacterium tuberculosis complex.
      The sequences of the IS6110 flanking regions from a M. tuberculosis strain
      harbouring four IS6110 copies were determined. Duplication of 3-4 nucleotides was
      found at the extremities of the four IS6110 copies, suggesting that IS6110 RFLP
      is due to transposition of the IS element. One of the copies of IS6110 analysed
      in the study was shown to be located at the same site in the genome of M.
      tuberculosis as the single copy present in an M. bovis BCG strain.

PMID- 1363677
TI  - Highlights of Gastroenterology in The Netherlands, 1992. Proceedings of a
      symposium. Istanbul, Turkey, 30 April-3 May, 1992.

PMID- 1363675
TI  - [A model of integrated therapy in the case of mutism in a chronic schizophrenic].

PMID- 1363678
TI  - The success of histamine-2 receptor antagonists.
AB  - The lives of both patients and doctors have been revolutionized since the
      development of histamine-2 receptor antagonists. Their development has
      introduced, for the first time, a rapid, reliable, and save means of healing both
      duodenal and gastric ulceration. The continuous administration of these agents
      has additionally been shown to reduce ulcer relapse and subsequent complications.
      In addition, they offer some protection from the development of nonsteroidal anti
      inflammatory drug-induced damage. The symptomatic relief of reflux together with
      healing of oesophagitis has been of further benefit. The drugs in this group have
      become one of the most widely used ethical pharmaceuticals in the world, with
      ranitidine (Zantac) as the biggest-selling drug in the world for the last few
      years. Their success can be attributed to their simplicity of use, safety, and
      above all, their efficacy. Their current role in gastroenterologic practice, in
      the face of new developments such as Helicobacter eradication and the development
      of proton pump inhibitors, will be discussed.

PMID- 1363679
TI  - Bionomics of important mosquito vectors in Malaysia.

PMID- 1363680
TI  - Global Spine and Head Injury Prevention Project (SHIP)

PMID- 1363681
TI  - [Experimental and clinical studies of carcinoprotective and immunomodulating
      effects of beta-carotene and other carotenoids. Proceedings of the Working
      Meeting. Moscow, September 17-18, 1991].

PMID- 1363682
TI  - [Surgical and logopedic functional rehabilitation after partial, sub-total and
      total laryngectomy. Round table. Sorrento, 9 June 1992].

PMID- 1363684
TI  - [Anaphylactic shock complicated by myocardial infarction: side effect of
      glaphenine?].
AB  - The authors report a case of anaphylactic shock complicated by coronary spasm and
      infarction attributed to glafenine medication in a 43-year-old male patient. The
      outcome was positive and coronary angiography showed healthy coronary vessels.
      The ergonovine maleate was negative. A review of the literature confirms the
      rarity of this complication of anaphylactic shock and study the ECG changes
      induced by this type of reaction and to analyze the mechanisms responsible for
      this coronary spasm in this situation. These consists basically of histamine
      release and prostaglandin-synthesis inhibition.

PMID- 1363683
TI  - [Takayasu disease. Diagnostic criteria and therapeutic procedure].
AB  - A study of 11 cases of Takayasu's disease, collected from the cardio-vascular
      surgical service of Sfax, has been realized during the 4 year-period from 1988 to
      1991. Womanly predominance was neat. The average age was 40 years, with extremes
      of 24 and 56 years. Dominant revealing symptoms was upper limb ischaemia found in
      9 cases, a reno-vascular hypertension rebelled to medical treatment was noted in
      2 cases. Arteriography have showed a preferential localization of lesions in the
      subclavian artery essentially at the post-vertebral segment. Lesions types were
      dominated by stenosis and obliteration, then aneurysms were rare. Operative
      indication was posed in 9 cases. 11 revascularisations procedures were performed
      of which 10 arterial by passes and one resection graft. Two bypasses were
      obstructed, the 9 remaining bypasses have a good previous checked clinically and
      by angiography (or echo-doppler) with a mean follow-up of 14 months.

PMID- 1363685
TI  - Overpressured layer chromatographic study of retention behaviour of various
      benzodiazepine derivatives on layers impregnated with tricaprylmethylammonium
      chloride.
AB  - The retention behaviour of various benzodiazepine derivatives was investigated on
      silica gel layers impregnated with tricaprylmethylammonium chloride (TCMA). The
      chromatograms were developed by means of overpressured layer chromatography
      (OPLC). As for the case of amino- and nitrosalicylic acids, pyrimidine
      derivatives, barbiturates, penicillins, cephalosporins and tetracyclines, the
      retention of benzodiazepine derivatives increased with increasing layer TCMA
      concentration with eluents containing methanol and water, but not TCMA. On
      increase of the methanol content of the eluent, a retention-decreasing effect was
      observed. On layers impregnated with TCMA, a linear relationship existed between
      the RM values of the benzodiazepines and the methanol content of the eluent. A
      similar relationship held for silica gel layers impregnated with paraffin oil
      (traditional reversed-phase). There was no correlation between the results
      obtained on layers treated with TCMA or with paraffin oil. On TCMA-impregnated
      layers, the retention of compounds having different chemical structures showed no
      dependence on the pH of the eluent. There were two reasons for this. Firstly, as
      it was established, above a certain RF value, the pH of the layer in the presence
      of TCMA was almost identical irrespective of the original pH of the buffer.
      Secondly, below this RF value, the actual pH of the layer did not have a strong
      enough effect to cause appreciable differences between the retentions of the
      dissociated and undissociated species of the analytes. The conditions for optimum
      separation are given.

PMID- 1363686
TI  - Analysis of ICI 118551, a new beta 2 blocking drug, and related compounds by RP
      HPLC-DAD.

PMID- 1363687
TI  - Drug Analysis 1992. Invited plenary, keynote and submitted papers from the 4th
      International Symposium organized by the Belgian Society of Pharmaceutical
      Sciences. Liege, Belgium, May 1992.

PMID- 1363688
TI  - Analysis of new serotonergic anxiolytics by liquid chromatography.
AB  - A simple isocratic procedure was developed for the analysis of new serotonergic
      anxiolytics and the related compounds in bulk materials, pharmaceutical
      formulations and in biological samples. The system may be applied for the assay
      of other serotonergic anxiolytics of related structure such as buspirone. The
      liquid chromatographic assay utilizes a reversed-phase C18 column, a mobile phase
      consisting of a mixture (55:45, v/v) of (A) buffer potassium dihydrogen phosphate
      (0.05 M) containing sodium lauryl sulphate (0.005 M) and (B) acetonitrile. A
      fluorescence detection is used with lambda ex 237 nm; lambda cm 374 nm. The
      accuracy, precision and sensitivity of the proposed method are established.
      Standard curves are linear with respect to concentration in the range 0.05-7.5
      micrograms ml-1. The method also allows the separation and identification of
      related compounds at concentrations below 0.01%.

PMID- 1363690
TI  - Resolution of several racemic 3-hydroxy-1,4-benzodiazepin-2-ones by high
      performance liquid chromatography on a chiral silica-bonded stationary phase.
AB  - The resolution of four racemic 3-hydroxy-1,4-benzodiazepin-2-ones, widely used in
      therapeutics, by means of a chiral stationary phase is described. The chiral
      selector used is (S)-N-(3,5-dinitrobenzoyl)phenylalanine. This chiral stationary
      phase showed both good enantioselectivity and efficiency for the compounds.
      Elution times were in all cases shorter than those previously reported for such
      compounds on different stationary phases. Racemic oxazepam was used to evaluate
      the loading capacity of the chiral stationary phase.

PMID- 1363689
TI  - Evaluation of six chiral stationary phases in LC for their selectivity towards
      drug enantiomers.
AB  - Six chiral stationary phases (CSP) were evaluated for their enantioselectivity
      towards a series of 45 drugs with different acidic, basic or neutral properties.
      These CSPs were: a polyacrylamide phase, Chiraspher; two polysaccharide-based
      phases, cellulose tris-3,5-dimethyl phenylcarbamate (Chiralcel OD) and the S
      naphthylethylcarbamate derivative of beta-cyclodextrin (SN-beta-CD; Cyclobond I
      SN); and three protein-based CSPs--alpha 1-acid glycoprotein (Chiral-AGP),
      ovomucoid (OVM) and cellulase. A total of 28 different mobile phases were
      involved. Chiral-AGP, OVM and Chiralcel OD appeared to be the most promising CSPs
      for the enantio separation of the series of structurally different compounds
      evaluated. Cellulase and Chiralcel OD show particularly high enantioselectivity
      towards the group of beta-blocker drugs. The different protein-based CSPs were
      used in their usual reversed-phase mode. The other phases were used in
      combination with apolar mobile phases, except for SN-beta-CD, which was evaluated
      in both modes. Formal optimization strategies were not adopted, although the
      effect of organic modifier and eluent pH on enantioselectivity was briefly
      examined for the protein-based phases.

PMID- 1363693
TI  - [Symposium on the treatment of renal failure with traditional Chinese medicine
      combined with Western medicine].

PMID- 1363692
TI  - [Silent myocardial ischemia and its combined therapy of traditional Chinese and
      Western medicine].

PMID- 1363691
TI  - Determination of meprobamate in pharmaceutical dosage forms also containing
      carbromal by liquid chromatography and indirect photometric detection.
AB  - In a pharmaceutical form also containing carbromal, meprobamate could not be
      quantified selectively by classical methods described in pharmacopoeias due to a
      significant interference from carbromal. Consequently, reversed-phase HPLC
      methods have been developed to separate the two active ingredients using indirect
      photometric detection to visualize and determine meprobamate which has very poor
      chromophoric properties. Different parameters influencing the sensitivity of the
      indirect response, such as the nature of the highly absorbing compound added to
      the mobile phase (the marker) as well as the methanol content and the pH of this
      phase, have been studied. Two chromatographic systems containing benzoic acid or
      cinnamic acid as the marker, have been optimized and validated. Good linearity
      and reproducibility have been obtained with both systems but the cinnamic acid
      method has the advantage that meprobamate and carbromal can be determined
      simultaneously at 273 nm.

PMID- 1363694
TI  - [Fetal liver transplantation in mice: tolerance induction by portal venous
      inoculation with allogeneic cells followed by injection of cyclophosphamide].
AB  - BALB/C mice (H-2d) receiving allogeneic C57 mice (H-2b) spleen cells via the
      portal vein (PV), followed by administration of cyclophosphamide (CY), abrogated
      the capability of rejecting allogeneic EL-4G- tumor cells (C57 origin). BALB/C
      mice received this combined treatment and BALB/C mice untreated or treated with
      either PV presensitization or CY injection were all exposed to 7.5 Gy total body
      irradiation, which was confirmed to be a lethal dose for BALB/C mice, then given
      intravenously 2 x 10(7) fetal liver cells from C57 mice (FLC57). The results
      indicated that the survival times of grafted BALB/C mice combined treatment were
      longer than those of untreated or either PV or CY treated, (PV + CY + 7.5Gy + FLC
      57: MST = 99.5 +/- 12.6 day), v(N + 7.5GY + FLC57: MST = 36.5 +/- 9.8 day; PV +
      7.5Gy + FLC57: MST = 12.2 +/- 0.2 day; CY + 7.5Gy + FLC57: MST = 27.6 +/- 5.5
      day). The difference was statistically significant. The spleen cells from the
      grafted mice were assessed by indirect immunofluorescence with anti-C57 serum.
      The spleen cells from BALB/C mice with survival time over 100 days after grafting
      of FLC57 in combined treatment group were about 70-80 percentage of C57 positive
      cells.

PMID- 1363695
TI  - [The choice of treatment in acute hemorrhagic necrotic pancreatitis: medical or
      surgical?].
AB  - In recent ten years, physicians and surgeons in Beijing Tong Ren Hospital
      cooperated well in the treatment of acute hemorrhagic necrotic pancreatitis.
      Twenty four cases were chosen to determine whether medical conservative or
      surgical operative treatment should be given. In the surgical operation group
      there were fourteen cases. Twelve cases survived and the remaining two died. In
      the medical conservative group only one of the ten cases died. The overall
      mortality of the twenty four cases of acute hemorrhagic pancreatitis was 12.5%.
      In our study, the indications for operation were as follows: (1) Presence of more
      than five positive diagnostic criteria. (2) Accompaniment of gall stone. (3)
      Inability to differentiate with other acute surgical abdominal emergencies such
      as intestinal obstruction.

PMID- 1363696
TI  - Traumatic dental injuries in normal and handicapped children in Nairobi, Kenya.
AB  - Two thousand, seven hundred and ninety one normal and handicapped children aged 5
      15 years were examined for traumatic dental injuries. Twelve percent had
      traumatised teeth while three percent had soft tissue injuries. More handicapped
      children (18%) than normal children (11%) had injuries. This study indicates that
      children need to be educated on preventive measures regarding traumatic dental
      injuries.

PMID- 1363699
TI  - International Symposium on Current Issues with Food Preservatives. Proceedings.
      Rome, Italy, 3-5 July 1991.

PMID- 1363697
TI  - [Neuropeptide interaction with other neurochemical systems in the integrative
      activity of the brain].

PMID- 1363698
TI  - [Adrenopeptide connections in the mechanisms regulating gastric secretory
      function in dogs].

PMID- 1363700
TI  - [Effect of poly-saccharide sulphate on thixotropic properties of whole blood in
      patients with cerebral thrombosis].
AB  - Using Low shear 30 rheometer, we measured the thixotropic parameters of blood
      from 30 patients suffering from cerebral thrombosis. The result showed that the
      yield stress (tau 0), non-Newtonian contribution of viscosity (eta s-mu) and
      viscosity of plasma (eta p) were significantly higher than those in the control
      group. Those patients were randomly divided into two groups. Each group included
      15 patients. The patients in group 1 and group 2 were treated with poly
      saccharide sulphate (PSS) and DX40 respectively by intravenous drip for 14 days.
      The results showed that tau 0, A, (eta s-mu) were significant decreased in group
      1 after treatment, but no significantly change in the thixotropic parameters was
      found in group 2 after treatment. The total curative rate in group 1 was higher
      than that in group 2. These results suggest that the patients with cerebral
      thrombosis had evidently increased degree of RBC aggregation. PSS could decrease
      the aggregation of RBC more significantly than DX40 did. It was probably one of
      the reasons why the therapeutic effect of PSS on cerebral thrombosis was better
      than that of DX40.

PMID- 1363701
TI  - Histologic case reports of coralline hydroxyapatite grafts placed in human
      intraosseous lesions: results 6 to 36 months postimplantation.
AB  - Four intrabony lesions from four patients were studied. Presurgical measurements
      included clinical attachment level, degree of recession, probing pocket depth,
      Plaque Index, Gingival Index, and Sulcular Bleeding Index. These measurements
      were also taken at 6-month intervals after surgery. Surgery involved exposing the
      intrabony defects by a papillary preservation technique, planing, and placing
      blocks of coralline hydroxyapatite. Three biopsy specimens and one block section
      were removed from the treated lesions at various periods ranging from 6 to 36
      months. Clinical and histologic observation provided evidence of osteogenesis
      around and through the coralline hydroxyapatite.

PMID- 1363702
TI  - Adhesins and receptors of Pseudomonas aeruginosa associated with infection of the
      respiratory tract.
AB  - Substantial progress has been made in defining a number of Pseudomonas adhesins
      which may be involved in the pathogenesis of respiratory infection. As yet, it is
      unclear which of these adhesins are primarily responsible for initiating
      infection in CF. The findings that CF epithelial cells have increased numbers of
      receptors for P. aeruginosa attachment and that CF epithelia are less highly
      sialylated than normal epithelial cells is consistent with a role for Pseudomonas
      pili in the initial recognition of asialoganglioside receptors on epithelial
      cells. In addition, there is ample evidence supporting the presence of several
      classes of non-pilus adhesins. Adherence properties of P. aeruginosa clearly vary
      from strain to strain and it appears likely that all potential adhesions are not
      equally expressed. More importantly, the regulation of the expression of these
      adhesins is unlikely to be constitutive. Some may be expressed only when
      triggered by the appropriate environmental conditions as found in vivo. In
      reviewing the pathogenesis of Pseudomonas infection in the CF lung, several
      classes of receptors must be considered. Pseudomonas infection is limited to the
      bronchi in CF. The organisms do not invade the bronchial tissue, but remain in
      the airways forming a biofilm with associated microcolonies. Thus, it would seem
      reasonable to expect Pseudomonas receptors within respiratory mucin. However, to
      date, there is little confirmatory data to support the presence of specific
      receptors in mucin. Alternatively, it is possible that the failure of bacterial
      binding to mucin components may contribute to colonization as organisms which are
      not efficiently cleared by muco-ciliary function may persist in the airways long
      enough to find or expose cryptic epithelial binding sites. This hypothesis is
      supported by binding studies which demonstrate decreased Pseudomonas attachment
      to CF as compared with normal respiratory mucins. Based on the available data,
      there appears to be a hierarchy of adhesin expression. Multiple ligand-receptor
      interactions may occur in the respiratory tract and it may be difficult to
      analyze the effect of secondary adhesins in the presence of what appears to be
      the dominant ligand, i.e. pilin. Thus, the failure to find the expected
      sialylated receptor for Pseudomonas attachment may be due to methodologic
      problems such as studying strains under conditions in which pili are well
      expressed and affinities for asialylated receptors predominate. This may not be
      the situation in vivo after the initial contact of the infecting organisms with
      the epithelial surface. Not only must the organism attach initially, but it must
      then be able to persist within the lung. Further studies, based on genetically
      defined mutants should help define which P. aeruginosa gene products and which
      components of the CF but not the normal epithelium are responsible for this
      unique but ultimately fatal host/bacterium interaction.

PMID- 1363704
TI  - Purification and characterization of Aeromonas sobria Ae24 pili: a possible new
      colonization factor.
AB  - Pili of Aeromonas sobria Ae24 were purified and characterized. The molecular mass
      of the pilin was estimated to be about 19 kDa by SDS-PAGE. The Ae24 pili were
      electrophoretically distinguishable from previously reported Aeromonas hydrophila
      Ae6 W pili and A. sobria Ae1 pili, although all three had indistinguishable
      morphology and shared a high degree of homology in the N-terminal amino acid
      sequences. Strain Ae24 and its purified pili adhered to rabbit intestine and
      agglutinated human and rabbit erythrocytes. Hemagglutination was inhibited by D
      galactose and D-mannose, but not by L-fucose. Organisms pretreated with Fab
      fraction of the antipilus antibody failed to adhere to the intestine. Organisms
      did not adhere to intestine pretreated with the purified pili. These findings
      suggest that the pili are a colonization factor of A. sobria Ae24 for the rabbit
      intestine, and that the receptor is galactose- and mannose-containing structure.

PMID- 1363705
TI  - Pathological status and therapy of HIV-infected hemophiliacs in Japan.
AB  - In Japan, 1531 out of 4171 hemophiliacs (36.7%) are human immunodeficiency virus
      (HIV)-infected, and up to 31 December 1991, 324 (21.2%) of these patients had
      developed AIDS. The Research Committee estimated the peak of the seroconversion
      period of hemophiliacs in Japan as January 1983, having presumed that new cases
      of seroconversion would not arise after heat treated concentrates came into
      general use in 1985. However, after a long 5 years window period starting in
      1985, cases of seroconversion are being reported. The present mean rate of
      reduction in cluster difference 4 (CD4) counts of HIV infected hemophiliacs has
      been increasing since 1990. At present (1991), the proportion of HIV infected
      hemophiliacs below 20 years is believed to be approximately 40%. Concomitantly
      with the aging of this group, the incidence of AIDS is expected to increase in
      the future. Although the aforesaid factors are conducive to a rising incidence of
      AIDS, the rate of increase of AIDS incidence among hemophiliacs in Japan is
      actually decelerating. This can, hopefully, be attributed to the commencement of
      widespread use of periodic pentamidine inhalation therapy, or the administration
      of drugs such as AZT (zidovudine) or ddI (didanosine) to AIDS related complex
      (ARC) cases, or to asymptomatic carrier (AC) cases with CD4 counts below 350
      cells for the prophylactic treatment against developing to AIDS. Oral
      administration of didanosine at a dosage of 400 mg/day, or didanosine at a dosage
      of 334 mg to 500 mg/day, has been found effective for the treatment of
      hemophiliacs with AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363706
TI  - Molecular heterogeneity of beta-thalassemia in Thailand.
AB  - beta-Globin genes in 294 chromosomes of beta-thalassemia homozygotes and patients
      of beta-thalassemia/HbE in the northeast, the middle and the south of Thailand
      were analyzed by the PCR related techniques: dot blot hybridization, direct
      restriction assay, direct cloning and direct sequencing of the amplified DNA
      fragments. Twelve different mutations were detected at various frequencies. They
      are an A-G at-28, codon 19 (AAC-AGC), a G-T at IVS-1 nt1,a G-C at IVS-1 nt5, a C
      T at IVS-2 nt654, a G addition in codons 8/9, a C deletion in codon 41, a 4 bp
      deletion in codons 41/42, an A addition in codons 71/72, an AAG-TAG in codon 17,
      a CAG-TAG in codon 26, a TAC-TAA in codon 35 and a 8 bp deletion in codons 123
      125. We also developed allele specific-polymerase chain reaction to facilitate
      non-radioactive detection of the mutation. Origins and spread of mutations are
      speculated based on the results of determination of haplotypes and frameworks
      that are linked to the thalassemia alleles.

PMID- 1363707
TI  - [Research--sharpening the purpose].

PMID- 1363703
TI  - Molecular localization of variable and conserved regions of pspA and
      identification of additional pspA homologous sequences in Streptococcus
      pneumoniae.
AB  - PspA is anchored to the surface of all pneumococci by the C-terminal end of the
      molecule. The N-terminal half of PspA is known to be serologically variable and
      to be able to elicit protective immune responses. Molecular analysis with DNA
      probes spanning different regions of pspA was carried out to identify homologous
      sequences among pneumococcal isolates. At high stringency, DNA probes derived
      from the 3'-half of pspA (encoding the C-terminal half of PspA) hybridized to all
      of 37 pneumococcal isolates tested, representing 20 capsular serotypes and 12
      PspA serotypes. Most strains had two sequences highly homologous to this region
      of pspA. Using derivatives of strain Rx1, with insertion mutations in pspA, it
      was possible to identify the functional pspA sequence. At 50% stringency, the 3'
      pspA probes also detected lytA and additional sequences. lytA encodes autolysin
      and shares homology with the 3' portion of pspA. A probe derived from the 5'-half
      of pspA (encoding the N-terminal half of PspA) hybridized with only 75% of
      strains and generally detected only one of the two sequences recognized by the 3'
      probes. Thus, the 3'-half of pspA appears to contain more highly conserved
      sequences than the 5'-half of pspA and shares homology with several additional
      sequences, suggesting that the pneumococcus might make several proteins that
      interact with the surface by the same mechanism as PspA.

PMID- 1363709
TI  - Report of round table on genetics and systematics of Trichinella (ICOPA VII,
      Paris).

PMID- 1363708
TI  - [Scientific-schooling conference on trichinosis].

PMID- 1363710
TI  - Function and modulation of the antennal heart of Periplaneta americana (L.).
AB  - The antennal heart of Periplaneta americana, a small accessory circulatory pump
      in the head, shows a rhythmicity with myogenic automatism. The muscle fibres
      extending throughout of the dilator muscle are electrically coupled. Among the
      peptides, proctolin causes a dose-dependent strong excitation, but allatostatin
      does not affect heart rhythm. However, allatostatin applied before proctolin
      antagonized the proctolin effect. In contrast to this, an immediate heart block
      produced by octopamine is similar to that produced by electrical stimulation of
      the nervus cardioantennalis. This inhibition is caused by a K(+)-dependent
      hyperpolarization. The second effect of octopamine is a delayed increase of the
      cAMP level. Because octopamine is present at the antennal heart, a physiological
      role is assumed.

PMID- 1363712
TI  - Neurotransmitters in the gastropod CNS: comparative immunocytochemistry.
AB  - The number, distribution, morphology, and projection areas of immunoreactive
      neurons labelled with different antisera were analyzed in the gastropod species,
      Aplysia californica, Lymnaea stagnalis and Helix pomatia, representing different
      levels of evolutionary development of the central nervous system. Our results
      show that the number of small-size peptidergic interneurons increases
      considerably in the cerebral ganglia of Helix, when compared to serotonin
      immunoreactive neurons. This phenomenon might be connected to the change from
      aquatic to terrestrial life, involving also a change in the composition and
      quality of sensory input, reaching the animal from the surrounding.

PMID- 1363711
TI  - Achatin-I, an excitatory neurotransmitter having a D-phenylalanine residue of
      Achatina giant neurones.
AB  - The neuroexcitatory peptide isolated from Achatina ganglia was identical to the
      synthetic Gly-D-Phe-L-Ala-L-Asp with respect to either the bioassay experiments
      using the Achatina neurones or the instrumental analysis (1H-NMR, SIMS, CD and
      HPLC). We termed it achatin-I (yield: 50 micrograms from 30,000 animals). Its
      stereoisomer, Gly-L-Phe-L-Ala-L-Asp, termed achatin-II, was also isolated from
      the ganglia (yield: 17 micrograms), but this was ineffective on the Achatina
      neurones. Of the eight possible stereoisomers, only achatin-I markedly showed
      excitatory effects on the two Achatina neurones, PON and TAN, and [D-Ala3]
      achatin-I (Gly-D-Phe-D-Ala-L-Asp) had the slight effects. Among the fourteen
      neurones tested, seven, including the two mentioned above, were excited by
      achatin-I, whereas no neurone was inhibited. Achatin-I produced an inward current
      (Iin) with an increase in the membrane conductance (g) under voltage clamp. ED50
      of achatin-I for exciting the neurones were 0.20-1.47 x 10(-5) M, and its Emax
      were 6.33-5.02 nA. Of the achatin-I analogues examined, only the three, Gly-Gly-D
      Phe-L-Ala-L-Asp, D-Phe-L-Ala-L-Asp and Gly-D-Phe-L-Ala-L-Asn, produced Iin, but
      much smaller than that of achatin-I. The equiactive molar ratios (EMRs) of the
      four effective related peptides (three analogues and a stereoisomer) vs. achatin
      I were: 8-60 for Gly-Gly-D-Phe-L-Ala-L-Asp, 200 - > 250 for D-Phe-L-Ala-L-Asp and
      > 200 for Gly-D-Phe-L-Ala-L-Asn and Gly-D-Phe-D-Ala-L-Asp. The Iin induced by
      achatin-I was blocked under the /Na+/0-free state, but unaffected under the
      [Ca2+]-free (replaced with Co2+), [Cl-]0-free or [K+]-enriched (3.0 x) medium,
      indicating that the Iin is produced by the gNa increase of neuromembrane. We
      propose that achatin-I having a D-phenylalanine residue is an excitatory
      neurotransmitter of the Achatina neurones.

PMID- 1363713
TI  - Respiratory behaviour in Lymnaea stagnalis: pharmacological and cellular
      analyses.
AB  - Using pharmacological and microelectrode approaches, evidence is presented here
      to suggest that exogenously applied dopamine can coordinate respiratory
      behavioural patterns and that its effects are reproduced using transmitter
      precursor such as L-DOPA. It is possible that dopamine reproduces sensory inputs
      to the respiratory network. Interactions between different transmitter substances
      underlie modifications of rhythmic discharges and enkephalins are able to
      modulate the respiratory rhythm.

PMID- 1363714
TI  - Immunoregulation of lymphoproliferation in vitro by monocytes and their
      subpopulations. II. Phenotypic changes of T cells in cultures activated with
      antigen and mitogen.
AB  - The aim of this study was to analyze phenotypes of T cells activated by mitogen
      (PWM) and antigen (PPD) in the presence of FcR+ or FcR- monocytes. It was found
      that CD4+ and CD8+ lymphocytes are preferentially activated in the presence of
      different monocyte subpopulations. Expression of HLA-DR and CD25 on CD4+
      lymphocytes was greater in cultures activated in the presence of FcR-. CD8+
      lymphocytes were more efficiently activated (expression of HLA-DR) when FcR+
      monocytes were added to culture. In the presence of FcR+ monocytes an increased
      expression of CD45RA antigen on CD4+ cells was also observed. These data support
      our previous functional studies which showed that "suppressor" T cells of CD8+
      phenotype are activated in the presence of FcR+ monocytes.

PMID- 1363715
TI  - Topochemical design of bioactive peptides and peptidomimetics.
AB  - For the studies of bioactive peptides, our laboratories have been employed an
      integrated approach including synthesis, bioassays, and conformational analysis.
      To obtain highly potent, selective and metabolically stable analogs,
      peptidomimetics such as peptide backbone modifications (retro-inverso
      structures), constrained amino acids, and cyclic structures have been
      incorporated into many bioactive peptide sequences. The conformational studies of
      the resulting analogs have led to topochemical models for the bioactivities of
      those peptides. This lecture will be focused on the results of such studies on
      opioids and somatostatin. We have synthesized numerous opioid analogs with
      various peptidomimetics based on three classes: enkephalins, dermorphin
      deltorphins, and morphiceptins. Many of these analogs exhibit high potency,
      selectivity, and metabolic stability. Conformational studies of these analogs
      have enabled us to define the structural characteristics necessary for
      bioactivities of morphiceptins, dermorphins, enkephalins, and deltorphins. From
      these results, we can propose conformational models responsible for bioactivities
      at the mu- and delta-receptors. Our studies of cyclic somatostatin analogs are
      based on the highly active Merck analog c(-Pro6-Phe7-D-Trp8-Lys9-Thr10-Phe11-)
      (where the superscripts denote position in native somatostatin). To investigate
      the topochemical preference of backbone and side chains, unusual amino acids,
      including beta-methylphenylalanine7 or 11, beta-methyltryptophan8, as well as
      backbone modifications such as retro-inverso structures have been incorporated.
      The bioactivity profiles of these peptidomimetic molecules provide much
      information on the effects of backbone and side chain constraints on bioactivity.

PMID- 1363716
TI  - hsp80 of Neurospora crassa: cDNA cloning, gene mapping, and studies of mRNA
      accumulation under stress.
AB  - Using mRNA isolated from Neurospora crassa mycelium, grown for 14 h at normal
      growth temperature of 28 degrees C, and heat shocked for 1 h at 48 degrees C, a
      cDNA library was prepared in the expression vector lambda gt11. Following
      immunoscreening of this library with a polyclonal antiserum raised against a 80
      kilodalton heat-shock protein (HSP80), cDNA clones containing 1.1- and 1.4
      kilobase inserts were selected. Analysis of the partial nucleotide sequence and
      the deduced amino acid sequence of the cDNA clones revealed a remarkable extent
      of homology with other eukaryotic stress-90 family proteins; 85% identity of the
      amino acid sequence with that of yeast HSP90(82) was seen. The C-terminal end of
      the sequence contained the MEEVD motif, characteristic of eukaryotic stress
      proteins with a predominantly cytosolic localization. The gene for N. crassa
      HSP80 was mapped to the right arm of linkage group V, using restriction fragment
      length polymorphism mapping. Its expression during heat shock and recovery was
      monitored by probing Northern blots of RNA isolated from mycelium grown under
      various stress conditions.

PMID- 1363718
TI  - DNA polymorphisms associated with the factor VIII:C gene in the Portuguese
      population.
AB  - We have determined the allele frequencies of seven restriction fragment length
      polymorphisms within or close to factor VIII:C gene in the Portuguese population.
      The allele frequency of all studied intra- and extragenic biallelic polymorphisms
      does not differ significantly from those found in other European or Asian
      populations. On the contrary, the distribution of the different alleles of the
      TaqI RFLP at the DXS52 locus revealed similarity only with Algerians. We observed
      a correspondence between the TaqI and BclI alleles at this locus.

PMID- 1363717
TI  - Restriction fragment length polymorphism at the CALCA locus identified by the
      probe pEMBL36 in immigrant populations of Australia.
AB  - Restriction fragment length polymorphisms detected by the cDNA probe, pEMBL36, at
      the CALCA locus (calcitonin gene and calcitonin gene related peptide) on TaqI
      blots were examined in samples from Italian, Greek and Vietnamese migrants to
      Melbourne, Australia and in a sample of residents from the island of Tasmania,
      Australia. The frequency of the rarer of the two alleles of this polymorphism, A2
      (8.0kb) varied between a low of 6% in Vietnamese to a maximum of 38% in
      Tasmanians. The frequency range of the A2 allele in European populations,
      however, was considerably less. Analysis revealed no significant heterogeneity
      for this polymorphism among either the European or European derived populations,
      and these combined data exhibited a frequency of 33% for the A2 allele. Though
      based on a very small Vietnamese sample this study suggests that the A2 allele is
      less frequent in those of Asian ancestry.

PMID- 1363720
TI  - Goosecoid and the organizer.
AB  - The molecular nature of Spemann's organizer phenomenon has long attracted the
      attention of embryologists. goosecoid is a homeobox gene with a DNA-binding
      specificity similar to that of Drosophila bicoid. Xenopus goosecoid is expressed
      on the dorsal side of the embryo before the dorsal lip is formed. Cells
      expressing goosecoid are fated to become pharyngeal endoderm, head mesoderm and
      notochord. Transplantation of goosecoid mRNA to the ventral side of Xenopus
      embryos by microinjection mimics the properties of Spemann's organizer, leading
      to the formation of twinned body axes, goosecoid is activated by dorsal inducers
      and not affected by ventral inducers. In the mouse, goosecoid is expressed in the
      anterior tip of the primitive streak. The availability of two early markers,
      goosecoid and Brachyury, opens the way for the comparative analysis of the
      vertebrate gastrula. The results suggest that the goosecoid homeodomain protein
      is an integral component of the biochemical pathway leading to Spemman's
      organizer phenomenon.

PMID- 1363721
TI  - Induction of anteroposterior neural pattern in Xenopus by planar signals.
AB  - Neural pattern in vertebrates has been thought to be induced in dorsal ectoderm
      by 'vertical' signals from underlying, patterned dorsal mesoderm. In the frog
      Xenopus laevis, it has recently been found that general neural differentiation
      and some pattern can be induced by 'planar' signals, i.e. those passing through
      the single plane formed by dorsal mesoderm and ectoderm, without the need for
      vertical interactions. Results in this paper, using the frog Xenopus laevis,
      indicate that four position-specific neural markers (the homeobox genes engrailed
      2(en-2), XlHbox1 and XlHbox6 and the zinc-finger gene Krox-20) are expressed in
      planar explants of dorsal mesoderm and ectoderm ('Keller explants'), in the same
      anteroposterior order as that in intact embryos. These genes are expressed
      regardless of convergent extension of the neurectoderm, and in the absence of
      head mesoderm. In addition, en-2 and XlHbox1 are not expressed in ectoderm when
      mesoderm is absent, but they and XlHbox6 are expressed in naive, ventral ectoderm
      which has had only planar contact with dorsal mesoderm. en-2 expression can be
      induced ectopically, in ectoderm far anterior to the region normally fated to
      express it, suggesting that a prepattern is not required to determine where it is
      expressed. Finally, the mesoderm in planar explants expresses en-2 and XlHbox1 in
      an appropriate regional manner, indicating that A-P pattern in the mesoderm does
      not require vertical contact with ectoderm. Overall, these results indicate that
      anteroposterior neural pattern can be induced in ectoderm soley by planar signals
      from the mesoderm. Models for the induction of anteroposterior neural pattern by
      planar and vertical signals are discussed.

PMID- 1363719
TI  - [Sulglycotide combined with H2-antagonists in the prevention of duodenal ulcer
      recurrence. Multicenter study].
AB  - The aim of the present study was to evaluate the role of sulglycotide, a molecule
      with gastroprotective properties, in monotherapy and in association with H2
      antagonists in the maintenance treatment of duodenal ulcer. The study was
      performed using a fully randomized experimental design. Following endoscopic
      confirmation, 626 patients with healed duodenal ulcer were treated for 6 months
      with sulglycotide 200 mg tid (293 patients) or sulglycotide + H2-antagonists (333
      patients). After 2, 4 and 6 months patients underwent a clinical control whereas
      an endoscopic control was performed after 6 months. The cumulative percentage of
      recidivation was 3.6% in the sulglycotide + H2-antagonist treated group, whereas
      the group treated with sulglycotide alone showed a recidivation rate of 15.4% (p
      < 0.001). These findings suggest the utility of combined sulglycotide and H2
      antagonist treatment in the maintenance therapy for duodenal ulcer.

PMID- 1363722
TI  - Xenopus Hox-2 genes are expressed sequentially after the onset of gastrulation
      and are differentially inducible by retinoic acid.
AB  - In this paper, we review experiments to characterise the developmental expression
      and the responses to all-trans retinoic acid (RA) of six members of the Hox-2
      complex of homeobox-containing genes, during the early development of Xenopus
      laevis. We showed that the six genes are expressed in a spatial sequence which is
      colinear with their putative 3' to 5' chromosomal sequence and that five of them
      are also expressed rapidly after the beginning of gastrulation, in a 3' to 5'
      colinear temporal sequence. The sixth gene (Xhox2.9) has an exceptional spatial
      and temporal expression pattern. The six genes all respond to RA by showing
      altered spatiotemporal expression patterns, and are also RA-inducible, the
      sequence of the magnitudes of their RA responses being colinear with their 3' to
      5' chromosomal sequence, and with their spatial and temporal expression
      sequences. Our data also reveal that there is a pre-existing anteroposterior
      polarity in the embryo's competence for a response to RA. These results
      complement and extend previous findings made using murine and avian embryos and
      mammalian cell lines. They suggest that an endogenous retinoid could contribute
      to positional information in the early Xenopus embryo.

PMID- 1363723
TI  - Expression of P-glycoprotein on normal lymphocytes: enhancement of the
      doxorubicin-sensitivity of concanavalin A-responding mouse spleen cells by P
      glycoprotein blockers.
AB  - The in vitro proliferative response of mouse spleen cells (SC) to the T-cell
      mitogen, concanavalin A (ConA), displays a doxorubicin (DOX)-resistant component.
      This T-cell proliferative response displays a much higher DOX sensitivity in the
      presence of novel potent inhibitors of P-glycoprotein (Pgp)-mediated multidrug
      resistance (MDR), the cyclosporin (Cs) derivative, SDZ PSC 833, and the semi
      synthetic cyclopeptolide, SDZ 280-446. Another resistance modulator, verapamil,
      might share this property, but its detection was impaired by the intrinsic
      toxicity of this calcium channel blocker for T-cell proliferation. A CD8+ cell
      depleted SC suspension displayed a higher sensitivity to DOX alone, as well as a
      different sensitivity profile to SDZ 280-446. The CD8+ cells that are sensitized
      to DOX by the resistance modulating agents (RMA) might correspond to a formerly
      described T-cell subpopulation with the MDR phenotype, which seems to be
      essentially constituted of CD8+ (cytotoxic) T cells. Our results may open the way
      to a novel form of immunomodulation combining classical antineoplastic agents
      with Pgp-blocking Cs analogs (even non-immunosuppressive ones), which may be
      particularly useful when treating acute graft rejection.

PMID- 1363724
TI  - Structure-activity studies of amsacrine analogs in drug resistant human leukemia
      cell lines expressing either altered DNA topoisomerase II or P-glycoprotein.
AB  - In an attempt to characterize and overcome tumor cell resistance to amsacrine (m
      AMSA), we studied the structure-activity relationships for amsacrine and seven of
      its analogs. Using the human leukemic cell line, CCRF-CEM, and its derivatives
      that express either P-glycoprotein (Pgp)-associated multidrug resistance (MDR)
      (CEM/VLB100) or altered topoisomerase II-associated MDR (at-MDR) (CEM/VM-1), we
      assessed antitumor effects of these drugs in a 48-hr growth inhibition assay. We
      also measured drug-topoisomerase II interactions in an intact cell assay that
      permits quantitation of drug-stabilized DNA-topoisomerase II complexes. We found
      that among the tested compounds, amsacrine has an intermediate effect on cell
      growth in all three cell lines. The CEM/VM-1 cells were 8.6-fold cross-resistant
      to m-AMSA, and the cross-resistance to the analogs was from 3.0- to 10.5-fold. In
      the CEM/VLB100 cells, the resistance pattern was different: several analogs,
      including amsacrine, showed little or no cross-resistance (0.5- to 2.8-fold),
      whereas for those compounds with substituents at position 3 on the acridine ring,
      resistance was relatively higher (9.9- or 16.2-fold). Substituents at this
      position substantially decrease the lipophilicity of the two compounds examined,
      probably because they both contain amino groups that would be charged at
      physiologic pH. Compound 12489, having a 1'-NHSO2C6H4NH2 substituent, was very
      potent in the three cell lines, showing only a slightly higher IC50 value in the
      CEM/VM-1 line and a lower IC50 value in the CEM/VLB100 and in the CEM
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363725
TI  - [Immune macrophage activation].

PMID- 1363726
TI  - Synthesis and biodistribution of the alpha 2-adrenergic receptor antagonist
      (11C)WY26703. Use as a radioligand for positron emission tomography.
AB  - The purpose of these experiments was to label an alpha 2-adrenergic receptor
      ligand with a positron emitting isotope and then test this radioligand in vivo.
      No-carrier-added [11C]WY26703 was synthesized by methylation of its desmethyl
      precursor, WY27050 with [11C]H3I followed by purification with HPLC in 14% yield
      in a synthesis time of 35 min from EOB. Ki values for unlabeled WY26703, ranged
      from 0.52-1.55 nM in tissues that express a single alpha 2-adrenergic receptor
      subtype. Tail vein injections of [11C]WY26703 in mice revealed that the compound
      was distributed in the brain, heart, lungs, spleen, and kidneys. In the brains of
      rats treated with atipamezole, an alpha 2-adrenergic receptor antagonist, there
      was no decrease in [11C] accumulation indicating a lack of observable specific
      binding of the radioligand. When brain tissue was homogenized and filtered,
      however, atipamezole decreased [11C] activity by 53%. Therefore, [11C]WY26703
      crosses the blood-brain barrier and specifically binds to alpha 2-adrenergic
      receptors with high affinity. Atipamezole treatment decreased only the area of
      the locus coeruleus [11C] value of the various regions of the brain. The
      affinity, however, of [11C]WY26703 does not appear to distinguish alpha 2
      receptors from nonspecific binding sites. PET study of [11C]WY26703 in a Rhesus
      monkey showed that influx of [11C]WY26703 into the brain was high for the first
      few minutes but radioactivity then declined rapidly and did not retain in a
      specific brain region. This suggests that [11C]WY26703 may not be a useful ligand
      for imaging human alpha 2-adrenergic receptors by positron emission tomography.

PMID- 1363727
TI  - [Medico-economic assessment of neuroleptics in schizophrenia. Amisulpride versus
      haloperidol].
AB  - The aim of this study is to assess the economic impact of neuroleptic strategies
      in the long-term treatment of schizophrenic patients. In this respect a new
      neuroleptic strategy (amisulpride) was compared to a reference drug (haloperidol)
      using a cost minimization method. Clinical, demographic and economic (direct
      medical costs) data were obtained retrospectively from patients' charts. Patients
      (n = 160) were randomly selected according to diagnosis (schizophrenia, DSM III
      R), treatment (outpatient, amisulpride or haloperidol) and follow up period (at
      least 6 months). The health insurance point of view was selected for the economic
      analysis. We found a significant reduction of the annual number of days of
      relapse when patients were treated with amisulpride compared to haloperidol. This
      reduction was associated with a significant reduction of direct costs mainly
      related to shorter length of hospitalization. This result was only partly
      explained by demographic and clinical variables such as the severity of the
      disease. The differences remained significant when populations were matched. This
      finding illustrates the validity of the concept of efficiency in psychiatry.

PMID- 1363728
TI  - [Excitatory amino-acids, a new class of neurotransmitters. Pharmacology and
      functional properties].
AB  - The pharmacology of excitatory amino acids (EAA) like glutamate or aspartate, has
      defined three main types of receptors: NMDA, quisqualate (now named AMPA) and
      kainate receptors, associated to cationic channels. The NMDA receptor, the best
      characterized, is a macromolecular complex with multiple specific sites: the
      agonist binding site (glutamate, aspartate, NMDA); the glycine site and polyamine
      site mediating allosteric regulations; the site located inside the channel for
      activity-dependent antagonists (phencyclidine, MK-801). This channel, permeable
      to calcium, is blocked by magnesium in a voltage-dependent manner. The structural
      complexity of the NMDA receptor suggests the existence of subtle regulations, but
      also offers many targets for pharmacological drugs. The calcium influx induced by
      NMDA receptor stimulation may account for the diversity of its functional
      properties. First, NMDA receptors modulate neuronal plasticity during the
      development and even long after. Indeed, NMDA receptor can induce long term
      potentiation (LTP; an experimental model of synaptic facilitation) and are
      involved in learning and memory. On the other hand, when over-stimulated, they
      induce neurotoxicity. The death of the cell occurs after several hours, during
      which NMDA antagonists can prevent irreversible damages. EAA systems are
      distributed in the whole brain, interacting with numerous other
      neurotransmitters, but particularly concentrated in the cortico-striatal and
      cortico-cortical fibers and in the hippocampus. Several neuro-psychiatric
      disorders could be related to a glutamatergic dysfunction: acute neuronal lesions
      (stroke, viral disease like AIDS) and epilepsy; but also chronic
      neurodegenerative disorders (Alzheimer's dementia, Huntington and Parkinson
      diseases). A glutamatergic hypothesis of schizophrenia arose from the
      phencyclidine model of psychosis, arguing for an imbalance between glutamate and
      dopamine. The therapeutic perspectives of glutamatergic substances in these
      diseases will be discussed.

PMID- 1363729
TI  - Glycosylation inhibits the interaction of invertase with the chaperone GroEL.
AB  - During refolding and reassociation of chemically denatured non-glycosylated
      invertase from Saccharomyces cerevisiae, aggregation competes with correct
      folding, leading to low yields of reactivation (Kern et al. (1992) Protein Sci.
      1, 120-131). In the presence of the chaperone GroEL, refolding is completely
      arrested. This suggests the formation of a stable complex between GroEL and non
      native non-glycosylated invertase. Addition of MgATP results in a slow release of
      active invertase from the chaperone complex. When GroEL/ES and MgATP are present
      during refolding, the final reactivation yield increases from 14% to 36%. In
      contrast, refolding of the core-glycosylated and the high-mannose glycosylated
      forms of invertase is not arrested by GroEL. Only a short lag phase at the
      beginning of reactivation and a slightly increased reactivation yield (64% to 86%
      for core-glycosylated and 62% to 76% for external invertase) indicate a weak
      interaction of the glycosylated forms with the chaperone.

PMID- 1363730
TI  - Peripheral blood stem cell transplantation: impact on procedure load and workload
      in an apheresis unit.
AB  - Peripheral blood stem cells (PBSC) reinfusion appears to hasten hematologic
      reconstitution following myeloablative therapy. While procurement of PBSC adds
      apheresis procedures, rapid engraftment could decrease the demand for platelet
      transfusions. To determine the impact of PBSC collection on workload in our
      apheresis unit, we studied 3 consecutive groups of patients with metastatic
      breast cancer given comparable high-dose chemotherapy and autologous bone marrow
      transplant, with or without PBSC or granulocyte-colony stimulating factor (G
      CSF). Forty-one transplants were performed with bone marrow cells only: 31
      patients (Group A) did not receive G-CSF, while the following 10 patients (group
      B) received daily G-CSF until neutrophil engraftment. Bone marrow cells and PBSC
      were used for the most recent 11 transplants (group C), followed by daily G-CSF
      until engraftment. PBSC were mobilized with cyclophosphamide (4 g/m2) and
      etoposide (1 g/m2), followed by G-CSF, 8 micrograms/kg/day. PBSC collection was
      carried out on a Fenwal CS3000+ cell collector, using modified procedure 1, to
      obtain a minimum of 5 x 10(8) mononuclear cells/kg. The times to neutrophil count
      over 500/microL, platelet count over 20,000/microL, and discharge from the
      hospital after transplant were significantly shorter for patients in group C
      (medians of 8, 8, and 21 days, respectively) compared to group A (medians of 14,
      14, and 29 days; P = 0.001) or group B (medians of 11, 24, and 32 days; P <
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363731
TI  - [Efficacy and tolerability of apraclonidine (ALO 2145, 1%) in the prevention of
      early ocular hypertonia, after trabeculoretraction using argon laser and
      posterior capsulotomy using Nd:YAG laser].
AB  - ALO 2145 (Apraclonidine Chlorhydrate)*, is a new hypotensive agent; it acts as a
      selective alpha-2-adrenergic agonist to produce a marked reduction in intraocular
      pressure with minimal effect on the cardiovascular system. 38 patients undergoing
      ocular laser surgery were allocated to treatment with either ALO 2145 1% (n =
      20), or to placebo (n = 18), in a double-masked fashion. One drop of study
      medication was instilled into the operative eye one hour before laser surgery,
      and one drop immediately after the laser surgery. ALO 2145 treated eyes exhibited
      a significantly lower mean intraocular pressure increase in the immediate
      postoperative phase, compared with placebo treated eyes. ALO 2145 also
      significantly reduced the postoperative incidence of intraocular pressure spikes,
      defined as intraocular pressure increases of more than 10 mmHg over baseline (17%
      of cases for active treatment vs 60% of cases for placebo). ALO 2145 1% was shown
      to be effective and well tolerated in the dosage regimen employed in this study.

PMID- 1363732
TI  - Pathogenesis of unstable angina with 0- or 1-vessel disease. Important role of
      coronary artery spasm.
AB  - In order to examine the possible role of coronary artery spasm in the
      pathogenesis of unstable angina, provocative testing for coronary spasm was
      performed in 43 patients with unstable angina who had 0- or 1-vessel disease.
      Coronary spasm was induced in 20 (65%) of 31 patients by hyperventilation testing
      (ST increases in 18, ST decreases in 2). Anginal attacks with either ST-segment
      elevation or ST-segment depression in patients without a significant organic
      stenosis were induced in 23 (55%) of 42 patients during treadmill exercise
      testing. Coronary artery spasm, showing severe (> or = 90%) vasoconstriction with
      angina and/or ischemic electrocardiographic ST-segment deviation, was also
      documented angiographically in 42 (98%) of 43 patients following intracoronary
      injection of acetylcholine. We conclude that dynamic coronary obstruction plays
      an important role in the genesis of attacks in patients with unstable angina who
      had 0- or 1-vessel organic coronary artery disease.

PMID- 1363733
TI  - Effects of denopamine with or without diltiazem on the ischemic heart of
      anesthetized dogs.
AB  - Effects of denopamine with or without diltiazem on the ischemic heart were
      investigated in anesthetized open-chest dogs. Partial occlusion of the left
      circumflex coronary artery (LCX) produced significant decreases in LCX flow and
      regional myocardial segment shortening rate (%SS) in the LCX-perfused area, and a
      significant increase in left ventricular enddiastolic pressure (LVEDP). Heart
      rate (HR) and mean aortic pressure (mAoP) were not altered, but aortic flow
      (AoF), positive first derivative of left ventricular pressure ((+)LVdP/dt),
      stroke volume (SV), stroke work index (SWI) and double product showed a tendency
      to decrease. Total peripheral vascular resistance (TPR) tended to increase.
      During coronary stenosis, saline infusion (vehicle group) did not change any
      parameter, but diltiazem infusion (diltiazem group) decreased HR, mAoP, TPR and
      double product and increased SV and SWI. Under these conditions, denopamine
      infusion produced increases in HR, mAoP, AoF, (+)LVdP/dt and double product and
      decreases in LVEDP and TPR in both groups. %SS in the left anterior descending
      coronary artery-perfused area was increased, but %SS in the LCX-perfused area was
      slightly decreased in both groups. SV and SWI were decreased by denopamine
      infusion in the vehicle group, while they were increased in the diltiazem group.
      Differences in changes in SV and SWI between the groups were statistically
      significant. Results suggest that combined treatment of denopamine and diltiazem
      may exert an advantage in alleviation of heart failure due to coronary stenosis.

PMID- 1363734
TI  - Correlation between cell-adherent activity and surface structure in Porphyromonas
      gingivalis.
AB  - The cell-adherent ability of 6 strains of Porphyromonas gingivalis (381, ATCC
      33277, SU63, KD1, W50 and W83) was compared by using radiolabeled bacterial cells
      and human gingival fibroblasts (Gin 1), human periodontal ligament fibroblasts
      (HPLF) and human epithelial cells (Ca9-22) that had been grown on collagen beads.
      The cell-adherent activity of these organisms varied among strains; P. gingivalis
      strains 381, ATCC 33277 and SU63 bound to the target cells at a range of 14% to
      72%, but the other 3 strains (KD1, W50 and W83) were scarcely bound (0.6% to
      3.5%). On the other hand, whole bacterial cells and culture supernatants of all
      strains showed distinct hemagglutinating activity. The 3 strains showing high
      cell-adherent activity were hydrophobic and the other strains showing less
      activity were relatively hydrophilic. Furthermore, a number of peritrichous
      fimbriae were found on the surface of P. gingivalis strains 381, ATCC 33277 and
      SU63, which showed high adherent activity, whereas, fimbriae on the other 3
      strains showing low adherent ability were barely apparent. Therefore, it was
      assumed that the cell-adherent activity of P. gingivalis was related to the
      hydrophobicity of the cell surface, which was related to the number of fimbriae.

PMID- 1363735
TI  - FimC, a chaperone-like periplasmic protein of Escherichia coli involved in
      biogenesis of type 1 fimbriae.
AB  - The product of the fimC gene of Escherichia coli K12 is required for the
      biogenesis of type 1 fimbriae. Mutations within the fimC gene abolish fimbrial
      synthesis. The FimC protein was found to be processed and the mature version was
      located in the periplasm. Unlike similar fimbrial systems, the major type 1
      fimbriae structural protein FimA was found to be significantly resistant to
      proteolytic degradation when present in the periplasm in a fimC- host background.
      The fimC gene was sequenced, and the deduced primary structure of the FimC
      protein was compared to other similar known proteins involved in the biogenesis
      of various fimbriae.

PMID- 1363737
TI  - [Effects of central neurotransmitters and neuromodulators on hypoxic ventilatory
      inhibition].

PMID- 1363736
TI  - Characteristics of haemolytic Escherichia coli with particular reference to
      production of cytotoxic necrotizing factor type 1 (CNF1).
AB  - A total of 1,106 Escherichia coli strains isolated in Spain between 1986 and 1991
      from extraintestinal infections and faeces of healthy controls were examined for
      production of alpha-haemolysin (Hly). Among strains causing urinary tract
      infections, sepsis and other extraintestinal infections, Hly production was
      detected in 51% (P < 0.001), 32% (P < 0.001) and 18% (P < 0.02), respectively. In
      contrast, only 9% of faecal isolates from healthy individuals synthesized Hly.
      The 356 haemolytic E. coli strains characterized in this study belonged to 28
      different serogroups. However, 284 (80%) were of one of eight serogroups (02, 04,
      06, 08, 018, 022, 075 and 083); 40% and 31% of haemolytic strains expressed P
      fimbriae and mannose-resistant haemagglutination (MRHA) type III, respectively.
      We have found that haemolytic isolates of E. coli may clearly be divided into two
      categories on the basis of the ability to produce cytotoxic necrotizing factor
      type 1 (CNF1). The serogroups and adhesins determined in Hly+CNF1+ strains were
      generally different from those found in Hly+CNF1- strains. Thus, serogroups 02,
      06 and 075 were associated with haemolytic E. coli producing CNF1+, whereas
      serogroups 01, 08, 018, 028 and 086 were established more frequently among
      Hly+CNF1- strains. While expression of P fimbriae was more frequently detected in
      Hly+CNF1- strains (70 versus 29%, P < 0.001), MRHA type III was usually
      identified in Hly+CNF1+ E. coli (42 versus 1%, P < 0.001). Furthermore, the sonic
      extracts of Hly+CNF1+ strains caused necrosis in rabbit skin (96 versus 25%, P <
      0.001) and death in intraperitoneally injected mice (73 versus 11%, P < 0.001)
      more frequently than sonic extracts of Hly+CNF1- strains.

PMID- 1363738
TI  - [Opioid peptides in spinal injury].

PMID- 1363739
TI  - [Role of cephalo-ventro-lateral region of medulla oblongata on stress
      hypertension].

PMID- 1363740
TI  - [Febrile convulsions: should some drugs be contraindicated?].
AB  - Should certain drugs be contraindicated in children who have had febrile seizures
      or who present a risk of convulsions? There are no publications dealing
      specifically with this problem. However, many drugs can induce convulsions and
      may be dangerous if they are associated with another determining factor (e.g.
      fever). Camphor known to be toxic and its use must be avoided in young children.
      Other terpenes given to children with colds may be convulsant if they are used
      for prolonged treatment or associated with other convulsant drugs
      (sympathomimetics, piperazine derivatives, antihistamines, etc.). On the basis of
      a retrospective study of 23 cases of febrile convulsion among 343 cases of
      infantile convulsion reported to the Poison Control Center and the
      Pharmacovigilance Center of Marseille between 1973 and 1991, we propose that
      camphor and sympathomimetics be avoided and that potential convulsant drugs and
      their association be used with caution. A prospective study is underway to
      determine responsibility of certain drugs in the occurrence of recurrence of
      febrile convulsions.

PMID- 1363741
TI  - [Arrhythmogenic effects of sultopride chlorhydrate: clinical and cellular
      electrophysiological correlation].
AB  - This study was designed following the first documented case of torsades de
      pointes induced by sultopride hydrochloride, a substituted benzamide neuroleptic
      drug. The patient, a 48 year-old woman with no known cardiovascular disease, had
      been treated for several years with this drug. She was admitted for severe
      bronchospasm requiring artificial ventilation. Twenty-one hours after her
      admission, she developed several episodes of torsades de pointes, which were
      successfully treated with magnesium sulphate. At that time, the QT interval was
      500 ms for a heart rate of 108 b.min-1 (QTc of 668 ms, and theoretical QTc 370
      ms). On the fourth day, QTc was 548 ms and theoretical QTc 370 ms. The sultopride
      was stopped on the fifth day. Two days later, QTc was 397 ms. Six months later,
      there was no recurrence. Several cases of TdP or sudden death have been reported
      in patients receiving neuroleptic drugs. The effects of sultopride hydrochloride
      were therefore tested on isolated ferret Purkinje fibres, using the
      microelectrode technique. Three concentrations of the drug (D1, D2, D3) were
      tested, as well as normal Tyrode solution. Maximum diastolic potentials (Vmax)
      were -88.37 +/- 0.89 mV (control), -89.08 +/- 1.20 mV (D1), -90.00 +/- 1.06 mV
      (D2), and -90.14 +/- 1.20 mV (D3). Vmax was not affected by sultopride during
      pacing at 1,000 ms of cycle length. The duration of the action potential
      increased with the drug concentration. There was no early after-depolarisation
      (EAD) during control, and 7 out of 9 fibers had EAD and 3 out of 9 triggered
      activity in D3. The solvent (benzyl alcohol) did not modify the action
      potential.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363743
TI  - Effect of a single exposure to ultraviolet B radiation on the alloreactivity of
      CD4+ and CD8+ cells.

PMID- 1363742
TI  - Dedication to Dr. Willem Johan Kolff. VIIIth World Congress of the International
      Society for Artificial Organs. Montreal, Canada, August 19-23, 1991.

PMID- 1363744
TI  - Family violence. Implications for the dental professional.

PMID- 1363745
TI  - Evidence for catecholaminergic control of alpha-melanotropin (alpha-MSH) content
      in hypothalamic areas.
AB  - A possible catecholaminergic regulation of hypothalamic alpha-melanocyte
      stimulating hormone (alpha-MSH) has been investigated in male rats by an in vivo
      approach. The hormone was measured by radioimmunoassay in three hypothalamic
      regions: medial basal hypothalamus, preoptic hypothalamic area and dorsolateral
      hypothalamus. The tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine
      (300mg/kg) increased the hypothalamic alpha-MSH content in medial basal
      hypothalamus and preoptic hypothalamic area when it was measured at 22:00 h.
      Diethyldithiocarbamate (600mg/kg), which inhibits dopamine beta-hydroxylase, as
      well as 2-3-dichloromethylbenzylamide (25mg/kg), which acts on the
      phenylethanolamine-NCH3 transferase also increased the alpha-MSH content in the
      above mentioned discrete areas. The alpha-adrenoceptor antagonist
      phenoxybenzamine (15mg/kg), as well as the alpha 1-adrenoceptor antagonist
      prazosin (1.0mg/kg), also increased the hypothalamic alpha-MSH content in medial
      basal hypothalamus and preoptic hypothalamic area. None of these agents modified
      alpha-MSH content in dorsolateral hypothalamus. Haloperidol (1.2mg/kg), a
      dopaminergic receptor antagonist, propranolol (6.0mg/kg) and yohimbine (10mg/kg)
      (non selective beta- and alpha 2-adrenergic antagonist drugs respectively) had no
      effect on the alpha-MSH in any of the hypothalamic areas studied. These results
      indicate that the catecholaminergic system is involved in the control of
      proopiomelanocortin derived hypothalamic alpha-MSH through an alpha 1
      adrenoreceptor. The data suggest that the control mechanism in the two alpha-MSH
      hypothalamic pools are different.

PMID- 1363746
TI  - Proceedings of symposia at the 89th Annual Meeting of the Japanese Society of
      Internal Medicine. Tokyo, April 2-4, 1992.

PMID- 1363747
TI  - Molecular analysis for the myotonic dystrophy mutation in neuromuscular
      disorders.
AB  - A variable expansion of an unstable CTG repeat has been identified as the causal
      mutation for myotonic dystrophy. Standard molecular genetic techniques can now
      supplement traditional assessment protocols in a variety of clinical neurological
      situations where diagnostic uncertainty prevailed. Southern analysis using DNA
      probes which identify the expanded sequence, supplemented by direct PCR analysis
      for repeat number, provides a specific sensitive diagnostic test for myotonic
      dystrophy.

PMID- 1363750
TI  - Proceedings of the 2nd International Conference on New Actions of Parathyroid
      Hormone. Pisa, Italy, May 22-25, 1991.

PMID- 1363748
TI  - [Tightly linked DNA probe for presymptomatic diagnosis and carrier detection of
      Wilson disease].
AB  - Haplotype analysis of the polymorphic loci, D13S26 and retinoblastoma (RB) gene
      which were closely linked to the gene responsible for Wilson disease (WD), was
      carried out to predict the presymptomatic stage or to detect carrier status in
      phenotypically normal sibs in 9 Chinese families with WD syndrome. By analysis of
      D13S26/HphI and RB/XbaI sites, 72% parents in these families were haplotypically
      heterozygote and therefore informative for linkage study. In 9 phenotypically
      normal sibs in these families, presymptomatic status was predicted with 99.2%
      confidence in 1 and excluded in 4. In the other 4 cases, 2 were unpredictable and
      2 were at least heterozygote and had 50% chance of being WD homozygote, depending
      on which chromosome they have got from their fathers.

PMID- 1363751
TI  - 1st Summer School in Immunotoxicology. Proceedings. Les Arcs, France, September
      14-16, 1992.

PMID- 1363749
TI  - [Comparison study on distribution of two types of hemorrhagic fever with renal
      syndrome (HFRS)].
AB  - IFAT-positive serum samples were typed by HI and divided into Appodemus-type
      (type A) and Rattus-type (type R). The results showed that in Pingdu and Jimo
      counties, the patients were mainly of type A, whereas in Junan and in Tengzhou
      counties, the patients were mainly of type R. The age distribution showed that
      96.0% of the type A patients belonged to age groups between 15-54 years, and no
      patients were younger than 15 years, or older than 65 years. The age distribution
      in type R patients, however, showed 76.5% of them were 15-54 years of age.
      Male/Female ratio was 3.3:1 in type A patients and 1.5:1 in type R patients. 80%
      of the type A patients were farmers. There were more housewives, students and
      children in type R than in type A patients. Type A patients usually occurred
      during Oct. and Dec. with only one peak in type A patients and two peaks in type
      R patients.

PMID- 1363752
TI  - Immunologic characteristics of fibrillary glomerulonephritis.
AB  - IgG and IgA immune complexes, mononuclear phagocytic system function, interleukin
      2 (IL-2) production by peripheral blood lymphocytes (PBL), serum-soluble IL-2
      receptors, tumor necrosis factor, beta 2-microglobulin and IL-1 beta, HLA-DNA
      polymorphisms, immuno-isoelectrofocusing, phenotype of PBL, lymphocyte
      cytotoxicity, activation of lymphokine-activated killer cells and natural killer
      cell activity were evaluated in 8 patients with tubular/fibrillary
      glomerulonephritis (GN). No common serologic, immunologic or immunogenetic
      features suggestive of plasma cell dyscrasias were found. No elements to state
      whether these GNs represent a new entity or just atypical forms of known GN were
      found.

PMID- 1363753
TI  - Partial coexistence of NADPH-diaphorase and somatostatin in the rat hypothalamic
      paraventricular nucleus.
AB  - Coexistence of NADPH-diaphorase (ND) activity and somatostatin (SRIF)
      immunoreactivity was studied in the paraventricular nucleus (PVN) of the rat
      hypothalamus by successive incubations of the same sections. ND was found in all
      PVN subdivisions, mainly in the magnocellular ones. SRIF was practically
      restricted to the parvicellular periventricular subdivision. Contrary to other
      brain regions where a wide SRIF-ND coexistence has been observed, the
      periventricular parvicellular subdivision was the only place of the PVN where
      some neurons colocalize both markers. The combination of the immunocytochemical
      and the histochemical labelings allows a further permanent and easy-to-perform
      parcellation of periventricular PVN neurons.

PMID- 1363756
TI  - [IV Conference on the Determination of Immunohistochemical and Morphometric Tumor
      Markers for Breast Neoplasms. Proceedings. Milano, 6-7 June 1991].

PMID- 1363754
TI  - The non-NMDA antagonist CNQX prevents release of amino acids into the rat spinal
      cord dorsal horn evoked by sciatic nerve stimulation.
AB  - Basal extracellular concentrations of 9 amino acids (AAs: aspartate, Asp;
      glutamate, Glu; asparagine, Asn; serine, Ser; glycine, Gly; threonine, Thr;
      alanine, Ala; taurine, Tau; and glutamine, Gln) were determined in the spinal
      cord dorsal horn of anesthetized rats using microdialysis and HPLC techniques.
      The concentrations of all measured AAs but Gln increased significantly (P < 0.05)
      during sciatic nerve stimulation at C-fiber strength. The concentration of Tau
      remained elevated following stimulation, while the other AAs returned to
      prestimulation values. Addition of the specific non-NMDA antagonist, CNQX, to the
      perfusing solution prevented the nerve stimulation-evoked AA release. Since the
      measured increases in extracellular AA concentrations are probably mainly due to
      activation of interneurons, these results suggest that blockade of non-NMDA
      receptors prevented activation of interneurons in the dorsal horn and support a
      major role of non-NMDA receptors at the first synapse of primary afferent fibers
      in the dorsal horn. Complete block of AA release and decreased basal levels of
      Glu after infusion of TTX into the dorsal horn also implies increased neuronal
      activity as the main source of higher AA levels during nerve stimulation.

PMID- 1363755
TI  - A double-label analysis demonstrating the non-coexistence of tyrosine hydroxylase
      like and GABA-like immunoreactivities in amacrine cells of the larval tiger
      salamander retina.
AB  - Previous studies have localized tyrosine hydroxylase, the rate-limiting enzyme
      for the production of dopamine, and gamma-aminobutyric acid (GABA) to amacrine
      cell populations in the larval tiger salamander retina. Double-label
      immunocytochemistry was used to examine if tyrosine hydroxylase-like and GABA
      like immunoreactivities colocalize in tiger salamander amacrine cells. A total of
      2,162 tyrosine hydroxylase-like immunoreactive amacrine cells were observed in
      double-labelled sections. None of these cells were observed to express GABA-like
      immunoreactivity. Therefore, the present study demonstrates that dopamine and
      GABA are localized to distinct neuronal populations in the larval tiger
      salamander retina.

PMID- 1363757
TI  - [HER-2/neu oncogene as prognostic factor in breast carcinoma].

PMID- 1363758
TI  - [Comparison of radiometric, immunometric, and immunohistochemical methods for the
      determination of hormonal receptors and quality control of other prognostic
      parameters in the characterization of carcinoma of the breast].

PMID- 1363760
TI  - [Absence of correlation between morphometric parameters and C-erb-B2 positivity].

PMID- 1363759
TI  - [Expression of proliferating cell nuclear antigen (PCNA) and its correlation with
      Ki-67, TfR, ET, PgR, pTNM in carcinoma of the breast].

PMID- 1363762
TI  - Abstracts of the Journees Scientifics du Club de l'Hemoglobine. Nancy, September
      14-15, 1992.

PMID- 1363763
TI  - [Role of long acting beta-mimetics in patients with chronic bronchitis and
      bronchial asthma].

PMID- 1363761
TI  - [Prognostic factors in breast carcinoma with special reference to the C-erb-B2
      gene: preliminary results].

PMID- 1363764
TI  - Proliferating cell nuclear antigen (PCNA) in atypical and malignant meningiomas.
AB  - Because it is not easy to determine the tumor status of meningiomas by current
      diagnostic procedures, we investigated these tumors immunohistochemically using
      the monoclonal antibody PC 10. This antibody recognizes a fixation- and
      processing-resistant epitope of the proliferating cell nuclear antigen (PCNA),
      which is a 36-KD nuclear antigen associated with the cell cycle. We studied
      paraffin-embedded and formalin-fixed tissue specimens of a group of 21
      atypical/malignant meningiomas together with 18 benign meningiomas. PCNA staining
      results were compared with the mean number of silver-stained nucleolar organizer
      region-associated proteins (AgNORs), tumor grading, and mitotic indices of these
      tumors. The percentage of PCNA-positive cells was found to range between 0.1% and
      40%, irrespective of the tumor grade. When all tumors were collectively
      considered, no positive correlation was found between PCNA scores and histologic
      grading and only a weak one between PCNA score and mitotic index. A higher
      correlation was seen between AgNOR counts and tumor grading. Our results suggest
      that PCNA labeling and histologic grading seem to be independent parameters. The
      correlations found between AgNOR counts and tumor grading should be substantiated
      in further series.

PMID- 1363765
TI  - XIV World Conference on Health Education. Helsinki, Finland, June 16-21, 1991.
      Abstracts.

PMID- 1363767
TI  - Alfentanil combined with vecuronium or pancuronium for use in eye surgery.
AB  - The usefulness of alfentanil for eye surgery, when combined with either
      vecuronium or pancuronium, was evaluated in 44 fit anticholinergized patients.
      Following thiopentone, four min after the administration of the relaxant (0.1
      mg/kg), and two min after the administration of alfentanil (15 micrograms/kg), a
      sixth of the patients bucked on introducing the endotracheal tube. The anesthesia
      for cataract extraction was maintained using alfentanil-relaxant-N2O in 18
      patients. In 16 of them, a low dose alfentanil regimen, occasionally supplemented
      with thiopentone, was satisfactory, and the recovery of alertness was rapid. In
      26 patients, alfentanil, 25 micrograms/kg, supplemented with isoflurane,
      efficiently obtunded the hemodynamic response after traction of extrinsic eye
      muscles at the commencement of major surgery. The patients receiving vecuronium
      presented with lower heart rates, than did those receiving pancuronium (P <
      0.05). During major operations, nodal rhythm was more frequent in the vecuronium
      group, than in the pancuronium group (P < 0.0001).

PMID- 1363766
TI  - Histochemical study of dipeptidylpeptidase IV in the nasal cavity organs of
      laboratory rodents and man.
AB  - The localization of dipeptidylpeptidase IV (DPP IV) activity was studied at light
      microscope level in the mucosa, glands and capillary endothelium of the human
      foetuses and rat, mouse and guinea pig in some prenatal and postnatal terms.
      Alkaline phosphatase reaction was used for complete histochemical demonstration
      of capillary endothelium. The two enzymes were mapped by Lojda's methods (12).
      The study brings knowledge of the localization of DPP IV activity in the nasal
      cavity structures and gives a different time survey of the onset of DPP IV
      activity during ontogenesis. Considering this activity we can presume that this
      membrane-bound protease DPP IV may participate in the metabolism of neuropeptides
      in the nasal cavity and play some role in immunological disturbances of patients
      with rhinitis.

PMID- 1363768
TI  - [Periarteritis nodosa and preleukemic states].

PMID- 1363769
TI  - Polyarteritis nodosa related to hepatitis B virus. A retrospective study of 66
      patients.
AB  - In an attempt to establish the characteristics, circumstances leading to
      infection and development of polyarteritis nodosa (PN) related to hepatitis B
      virus (HBV), prognostic factors and outcome, and to define the most effective
      treatment, 66 patients observed between 1972 and 1989 were analyzed. Hepatitis
      was clinically present in 19/66 patients before PN. In most cases, PN occurred
      less than 6 months after infection. Clinical manifestations of PN were comparable
      to those observed in patients without HBV infection except for orchitis which was
      present in 13.6% and for pulmonary signs which were absent. Transaminases were
      normal in 38 cases for SGOT and 31 for SGPT and twice the normal range or more in
      the other cases. Antineutrophil cytoplasmic antibodies (ANCA) were tested in 22
      patients and present in 2 (9%). Twenty-eight patients were treated with
      prednisone +/- oral cyclophosphamide +/- plasma exchanges. Thirty-eight patients
      were given a short-term treatment with prednisone followed by the association of
      vidarabine, 15 mg/kg bw/d for one week and 7.5 mg/kg bw/d for 2 weeks, and plasma
      exchanges: 14 sessions during the 3 weeks of vidarabine infusion, then tapered
      until stopping treatment after 2 to 3 months depending upon the clinical results
      obtained. The mean duration of follow-up was 50.3 +/- 46.1 months. At the end of
      follow-up, 13 of the 28 patients (46.4%) treated with steroids +/-
      cyclophosphamide +/- plasma exchanges died and 7/38 (18.4%) of those treated with
      vidarabine and plasma exchanges (p < 0.001) died. HBe/anti-HBe seroconversion was
      observed in 2 patients treated with prednisone +/- cyclophosphamide +/- plasma
      exchanges who were alive at the time of final analysis and in 16 patients
      receiving the other regimen. The outcome of patients treated with a few days of
      prednisone, vidarabine and plasma exchange was good and, therefore, we propose
      this protocol as the first viable treatment for polyarteritis nodosa related to
      HBV, surpassing the conventional treatment with steroids and cyclophosphamide,
      which stimulates viral replication.

PMID- 1363770
TI  - Catecholamine modulation of magnesium plasma levels in the rat.
AB  - Epinephrine (0.3 microgram/min) or isoproterenol (0.2 microgram/min) were infused
      for 40 min in rats to determine the role of catecholamines in the short-term
      control of plasma magnesium levels. Phentolamine (0.2 and 1 mg/kg) or propranolol
      (5 mg/kg), injected i.p. 10 min following the beginning of the infusion with
      catecholamines, were used to block alpha- or beta-adrenoceptors. Epinephrine
      alone elevated the systolic while decreasing the diastolic blood pressure and
      initially increased heart rate by 8% to 455 +/- 25 beats/min. Plasma potassium
      declined by 24% but magnesium levels remained constant. Following 0.2 mg/kg of
      phentolamine, systolic and diastolic blood pressure decreased by 40% and 55% to
      95 +/- 11 and 39 +/- 3 mmHg, respectively. Potassium levels were further reduced
      by 8%. Administration of this dose of phentolamine increased magnesium levels by
      8%. Magnesium levels were elevated by 19% to 2.38 +/- 0.20 mEq/l after 1 mg/kg of
      phentolamine, possibly due to excessive hemodynamic derangements. Propranolol
      reversed the hypokalemic and hemodynamic effects of the epinephrine infusion
      without altering plasma magnesium. Similarly, propranolol abolished the
      tachycardia and hypokalemia elicited by isoproterenol without affecting magnesium
      levels. These results suggest that catecholamines play no major role in the short
      term control of plasma magnesium in the rat.

PMID- 1363771
TI  - [Long-term outcome of a hospital series of patients with atrio-ventricular
      accessory pathway].
AB  - Ninety five patients with a mean age of 39 +/- 19 years, 82 of whom were
      symptomatic, having an accessory atrioventricular bidirectional conduction
      pathway (WPW syndrome: 77; "concealed": 18) were followed up for an average of
      7.3 +/- 2.6 years. The objectives were to analyse: the incidence and causes of
      death and the possible predictive factors of death due to the WPW syndrome--the
      influence of medical treatment and type of medication on survival and symptoms.
      Of the 8 cardiac deaths, 6 seemed to be related to the WPW syndrome, a prevalence
      of 7.8% and an annual incidence of 1.1/1000. The main risk factors which were
      identified were: age 62 +/- 8 years versus 37 +/- 15 years in survivors; p < 0.02
      -associated organic heart disease, especially ischaemic heart disease (5/6)--the
      description of severe symptoms, in particular recurrent syncope--documented
      malignant spontaneous or induced arrhythmias (5/6)--anterograde AV conduction
      with an effective refractory period < or = 230 msec in 4, though it was only 270
      msec in the other 2 patients, indicating that this parameter is not specific-
      amiodarone (6/6) did not prevent the fatal outcome in this particular group of
      patients. In the "benign" forms, only betablocker drugs could significantly
      reduce the frequency and severity of symptoms, especially when compared with
      Class I or IC antiarrhythmics. These results suggest that the indications of
      radical treatment should be widened in high risk patients, especially when
      elderly and with associated coronary artery disease. They also suggest that the
      role of betablocker drugs should be reevaluated in the so-called "benign"
      symptomatic forms.

PMID- 1363773
TI  - Effect of neutrophils on the growth of human pre-S1-reactive T-cells in vitro.
AB  - Granulocyte factor (GF) derives from the specific granules of polymorphonuclear
      neutrophils. GF possesses an immunoregulatory activity and augments the immune
      response to antigens in vitro and in vivo. The Pre-S1 sensitive T-cells reactive
      to Pre-S1 protein in vitro were developed from peripheral blood mononuclear cells
      of hepatitis B convalescent by in vitro Pre-S1 protein stimulation. The GF
      involvement in the activation and development of the Pre-S1 specific regulatory T
      cells in vitro was studied.

PMID- 1363772
TI  - [Which anti-ischemic treatment can be prescribed during and after the acute phase
      of myocardial infarction?].
AB  - After myocardial infarction, calcium channel blockers are the most prescribed
      anti-ischemic drugs followed by nitrate derivatives and beta blockers. In order
      to assess whether this attitude is justified by published data on their efficacy,
      a meta-analysis of trials of anti-ischemic drugs in myocardial infarction was
      performed. The early mortality was 13.3% in the group treated by IV nitrates in
      the acute phase of myocardial infarction and 17.2% in control groups, reducing
      the risk by a quarter (95% confidence interval of the odds ratio (CI): 0.55
      0.95). When all nitrate derivative trials were grouped together, the reduction in
      the risk of death of 21% was significant (from 15% to 11.8%) (CI: 0.59-0.94).
      Although oral nitrate derivatives introduced during the acute phase and continued
      for several weeks induced a non-significant reduction in mortality of 16%, when
      given intravenously, the benefits on early and longer term mortality were
      unquestionable. The mortality was 9.8% in the groups treated by calcium channel
      blockers and 9.3% in control groups (NS); the recurrent infarct rate was 4.8% and
      5.4% respectively (NS). In this family of drugs, there was no product which
      distinguished itself from the others with regard to beneficial or adverse
      effects. The early mortality decreased from 9.2% to 8.2% in the groups treated by
      oral beta-blockade--a risk reduction of 10% (NS) and from 4.2% to 3.7% with
      intravenous beta-blockers--a risk reduction of 12% (p = 0.03). Late mortality
      decreased from 9.4% to 7.6%, a reduction of 20% (p < 0.00001) in long term
      trials.2+ contraindication of betablockers in patients without cardiac failure.

PMID- 1363774
TI  - [Pharmacologic defense of the brain in radiation injury: some arguments].
AB  - Based on an analysis of the latest data on the problem of pharmacologic defense,
      the pro and contra scientific arguments of using pharmacochemical countermeasures
      to radiation damages of the brain are discussed in succession. A comparative
      characteristic of positive and negative effects of countermeasures possessing
      various neurotropic properties is presented. A general scheme of searching for
      the means of pharmacologic correction of radiocerebral syndrome involving the
      following stages: pathophysiologic analysis of cerebral disorders; selection of
      behaviorally significant (psychophysiologic) criteria; search for
      pharmacochemical correction means; experimental animals studies with
      extrapolating their results to a man; radiocerebral syndrome simulation
      (pharmacologic, physical and chemical); field tests; decision-making (medico
      biological and formalized approaches) is presented. "Pyramid of complexity" of
      radiocerebral effects extrapolation from the animals to a man to suit an
      hierarchy of the biological structures is presented. The effectiveness of
      conditionally-quantitative relationships of the drugs of prolonged and short-term
      effect as applied to various radiation syndromes (erythropoietic,
      gastrointestinal and cerebral) is discussed.

PMID- 1363775
TI  - Quality of life after open heart surgery 16-18 May 1991.
AB  - This is a review of papers presented at the international symposium on 'Quality
      of Life after Open Heart Surgery' comprising the experience in more than 20,000
      patients. Early identification and operation of premorbid personalities,
      psychological counselling before and after the operation, explanation of true
      risks, an educational programme in redefinition of family roles, stressing the
      importance of returning to normal activity in education, employment and society,
      financial support through health insurance to cover the high cost of open heart
      surgery, and formulating socioeconomic policies which encourage returning to work
      yield improvement in all patient groups. Specific to valve replacement is patient
      participation in deciding the kind of prosthesis and improvement of
      anticoagulation strategies. Coronary bypass patients benefit broadly through a
      comprehensive rehabilitation programme. For congenital heart disease, emphasis
      was laid on the need to educate parents about the disease, the importance of open
      discussion between parents, the patient and the paediatric cardiologist, and the
      function of a parents' self-help group. For heart transplantation the endeavour
      must be to increase donor availability and to develop better immunosuppression
      schedules. Lastly, general awareness of patients' abilities will facilitate their
      social integration and improve their quality of life.

PMID- 1363777
TI  - First European Conference on Pain Research--Brussels, December 11-13 1991.

PMID- 1363776
TI  - Report from a National Cancer Institute (USA) workshop on quality of life
      assessment in cancer clinical trials.
AB  - To promote the inclusion of quality of life (QOL) end-points in clinical research
      on cancer, the National Cancer Institute (USA) sponsored a workshop on QOL
      assessment in cancer clinical trials in July, 1990. Experts in clinical trials
      and QOL research formed four working groups to identify current areas of cancer
      treatment in which QOL end-points are most important; to discuss methodologic
      problems in QOL assessment; to address common problems in implementing clinical
      studies with QOL end-points; and to consider statistical issues in design,
      implementation, and data analysis. Recommendations made by the working groups are
      summarized in this paper.

PMID- 1363779
TI  - CEB 13 detects a VNTR locus (Het: 93%) on chromosome 7q.

PMID- 1363778
TI  - Gene targeting for somatic cell manipulation: rapid analysis of reduced
      chromosome hybrids by Alu-PCR fingerprinting and chromosome painting.
AB  - The techniques of reverse genetics rely heavily on parasexual methods for
      manipulating the human genome. However, the application of somatic cell genetics
      is severely limited by the availability of suitable endogenous selectable markers
      in the genome. We have addressed this problem by targeting a universally
      selectable marker into a predetermined region of the genome, using a stringent
      selection for homologous recombination. Correct gene targeting to human
      chromosome 7q11 was screened for by Southern blotting and confirmed by
      fluorescent in situ hybridization. Reduced chromosome 7 hybrids were generated by
      chromosome mediated gene transfer and selection for the neo gene. The resultant
      transgenomes were characterized by a combination of L1 fingerprinting, locus
      specific marker analysis, Alu-PCR and chromosome 'painting'. Alu-PCR and L1
      'fingerprints' are complementary and mutually consistent. Chromosome 'painting'
      reflects and extends the results obtained for specific marker co-transfer. Thus
      Alu-PCR 'fingerprinting' and 'painting' combine to rapidly provide an accurate
      picture of transgenome content and complexity. Gene targeting, chromosome tagging
      and subsequent isolation can be applied to any region of the genome for which a
      molecular probe is available.

PMID- 1363781
TI  - Probe D16S273 detects a PstI RFLP with 8 alleles.

PMID- 1363780
TI  - De novo mutation in the COL4A5 gene converting glycine 325 to glutamic acid in
      Alport syndrome.
AB  - Southern blot analysis of the COL4A5 gene in a 6 year old Italian Alport patient
      (proband VIZ) showed the loss of an MspI site that was present in the mother and
      control DNAs. PCR amplification and DNA sequencing revealed a single G-->A
      nucleotide change. The mutation results in substitution of a glutamic acid for a
      glycine residue at position 325 in the triple helical region of the alpha 5(IV)
      chain.

PMID- 1363782
TI  - Two hot spots of recombination in the DMD gene correlate with the deletion prone
      regions.
AB  - Genetic mapping has indicated that meiotic recombination occurs about 4 time more
      frequently in the dystrophin gene than expected on the basis of its length. To
      detect where recombinations occur within the gene, we have studied the CEPH
      families panel using highly polymorphic microsatellite markers located at the
      ends of the gene or flanking the major deletion hot spot in intron 44. We found a
      major hot spot of recombination between markers STR44 and STR50(1), i.e., between
      exons 44 and 51. Within this hot spot, a peak of recombination was located in the
      large intron 44. A second minor recombination prone region was found between DXS
      206, (XJ, in the large intron 7) and the 5' end of the DMD gene. The distribution
      of the recombination events in the gene of healthy individuals was very similar
      to that of deletion breakpoints in DMD/BMD patients, suggesting that the two
      phenomenon may share a common mechanism. These results should also improve
      efficiency and accuracy of linkage analysis applied to carrier detection and
      prenatal diagnosis. In particular, if markers located at the very 3' end of the
      gene are not informative, the highly polymorphic ones located between exons 50
      and 60 can be used instead of presently available extragenic markers, with a very
      low risk of diagnostic error due to recombination.

PMID- 1363784
TI  - Human BglII/BclI RFLP recognized by 5' region of human MAP 2 gene probe.

PMID- 1363783
TI  - Mapping of the formin gene and exclusion as a candidate gene for the autosomal
      recessive form of limb-girdle muscular dystrophy.
AB  - Limb-Girdle Muscular Dystrophy (LGMD) is a myopathy with clinical and
      transmission heterogeneity. The recessive form, LGMD2, has been recently mapped
      by linkage analysis to 15q. As an attempt to identify the gene involved in this
      pathology, we tested as candidate gene the LD locus, called LD for limb
      deformity. This gene has recently been identified and mapped to chromosome 15q13
      q14. It is homologous to the murine formin gene which is localized to mouse
      chromosome 2. Mutations in this murine gene have been shown to cause limb
      deformity and kidney defect. YAC clones containing the LD gene were isolated and
      utilised to confirm the cytogenetic localisation. Internal DNA polymorphisms of
      the LD locus were analyzed in LGMD2 and CEPH families. The LD gene was mapped
      between the alpha cardiac actin gene and the D15S24 locus. Crossovers between the
      LGMD2 and the LD loci excluded the LD gene as a candidate for LGMD2.

PMID- 1363785
TI  - TaqI RFLP in the region of the human homeobox PBX3 gene.

PMID- 1363786
TI  - Analysis of exon 7 of the human phenylalanine hydroxylase gene: a mutation hot
      spot?
AB  - Complete sequence analysis of 194 human phenylalanine hydroxylase genes from PKU
      patients originating from West Germany and Bulgaria revealed 13 different
      mutations within exon 7 of the gene. Four of these mutations (T238P: ACT-->CCT;
      L242F:CTC-->TTC; R252G:CGG-->GGG; and 1043 delta 11: nt 1043-nt 1053 deleted)
      have so far not been described in the literature. Including these new mutations
      at least 21 different gene lesions and one sequence polymorphism exist for exon
      7. Despite this large number unbiased calculation of the mutation frequency/exon
      size ratio does not provide conclusive evidence that exon 7 is a hot spot for
      disease causing mutations. Extensive screening during our experiments also failed
      to demonstrate the existence of excessive polymorphism in this part of the gene.
      It might therefore be speculated that the functional importance of the highly
      conserved exon 7 sequence accounts for the clustering of observed mutations which
      result in clinically manifest PKU. In addition we report our experience in regard
      to the resolution capacity of denaturing gradient gel electrophoresis (DGGE), a
      nonradioactive technique for the rapid screening of unknown mutations in exon 7.

PMID- 1363787
TI  - Modulation of lipoprotein lipase activity in the rat by the beta 2-adrenergic
      agonist clenbuterol.
AB  - This study evaluated the effects of beta 2-adrenoceptor stimulation on some
      determinants of triglyceride metabolism. Male Sprague-Dawley rats were injected
      twice daily with clenbuterol (30 micrograms.kg-1) for 7 days, or with an
      equivalent volume of vehicle. Serum triglycerides, hepatic triglyceride secretion
      rate, and lipoprotein lipase activity in white and brown adipose tissues as well
      as in red vastus lateralis muscle and heart were evaluated in the fasting state
      and following a fat-free, high-sucrose meal, 3 h after the last agonist
      injection. In rats killed in the fasting and postprandial states, clenbuterol
      reduced the mass of white adipose tissue (-25 and -12%, respectively; p < 0.02),
      whereas it increased the mass of vastus lateralis muscle (+11 and +7%; p < 0.002)
      and heart (+13 and %; p < 0.0001). In vehicle-injected animals, the fasting state
      was associated with lower lipoprotein lipase activity in white and brown adipose
      tissues, and higher enzyme activity in vastus lateralis and heart, compared with
      the postprandial state. Postprandially, treatment with clenbuterol reduced
      lipoprotein lipase activity in white adipose (-24%), whereas it increased enzyme
      activity in brown adipose (+107%) as well as in vastus lateralis (+35%). In
      fasted animals, no significant variation of enzyme activity in these tissues was
      observed following clenbuterol treatment, whereas in the heart, a decrease of
      lipoprotein lipase activity was observed (-22%). Clenbuterol lowered serum
      triglycerides significantly (-23%), but not their rate of secretion, whereas the
      agonist decreased the insulin to glucagon ratio only in the postprandial
      state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363788
TI  - Regression of left ventricular hypertrophy--are there differences between
      antihypertensive agents?
AB  - Echocardiographically determined left ventricular mass (LVM) is currently
      considered to be the most powerful risk indicator for cardiovascular disease,
      yielding prognostic information beyond that provided by the evaluation of
      traditional cardiovascular risk factors, high blood pressure included. It has
      been considered logical to try to obtain regression of cardiac hypertrophy, even
      though the risk-reducing implications of such a measure remain to be fully
      established. Experimental and clinical studies have shown that some classes of
      antihypertensive compounds are less effective than others in causing reversal of
      left ventricular hypertrophy (LVH) in spite of being similarly efficacious in
      lowering blood pressure. In order to extract the maximum amount of information
      from clinical studies, a meta-analysis was performed. This analysis included 109
      treatment studies, each conformed to strict present rules. Only studies with
      pharmacological antihypertensive therapy and echocardiographically determined LVM
      were included. An analysis of the effect of the four first-hand antihypertensive
      treatment principles, adjusted for differences between studies with ANCOVA,
      showed that the ACE inhibitors, beta-blockers and calcium antagonists all reduce
      LVM by reversing wall hypertrophy and that the effect is most pronounced with ACE
      inhibitors. Diuretics reduce LVM mainly by a reduction in left ventricular
      diameter. If the difference in ability to reverse LVH, between ACE inhibitors and
      beta-blockers/diuretics would correspond to a difference in prognosis, then the
      outcome of antihypertensive therapy might be expected to improve. This hypothesis
      is currently under investigation.

PMID- 1363790
TI  - Molecular cloning and cDNA sequence analysis of coho salmon stanniocalcin.
AB  - Stanniocalcin (STC) (formerly known as both teleocalcin and hypocalcin) is an
      anti-hypercalcemic, glycoprotein hormone that is produced by the corpuscles of
      Stannius (CS), endocrine glands that are confined to bony fishes. The hormone has
      a unique amino acid sequence and exists as a disulfide-linked homodimer in the
      native state. In previous studies, we have described the purification and
      characterization of two salmon STCs, and examined the regulation of hormone
      secretion in response to calcium using both in vitro and in vivo model systems.
      This report describes the molecular cloning and cDNA sequence analysis of a coho
      salmon STC messenger RNA (mRNA) from a salmon CS lambda gt10 cDNA library. The
      STC mRNA in salmon is approximately 2 kilobases in length and encodes a primary
      translation product of 256 amino acids. The first 33 residues comprise the prepro
      region of the hormone, whereas the remaining 223 residues make up the mature form
      of the hormone. One N-linked, glycosylation consensus sequence was identified in
      the protein coding region as well as an odd number of half cysteine residues, the
      latter of which would allow for interchain bonding or dimerization of monomeric
      subunits. In addition, three sites were identified in the mature protein core of
      STC (two dibasic, one tribasic) that may be acted upon by endopeptidases to
      produce truncated forms of the hormone. In support of this latter possibility,
      Western blot analysis revealed multiple molecular weight forms of sTC within
      salmon glands.

PMID- 1363791
TI  - Muscarinic involvement in the regulation of gonadotropin-releasing hormone in the
      cyclic rat.
AB  - The release of gonadotropin-releasing hormone (GnRH) from the median eminence
      (ME) in cyclic rats was stimulated to a significant extent by the selective
      muscarinic antagonists 11[(2)(diethylamino)methyl][-1-piperidinyl]-acetyl-5, 11
      dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX-116) and methoctramine,
      and to a lesser extent also by other ligands selectively antagonistic to m1 and
      m3 receptors. Such stimulation was estrous-cycle-dependent and was not achieved
      by muscarinic agonists. We suggest that the effect is induced via the m4 receptor
      subtype. Attempts to block the muscarinic-antagonist-induced stimulation of GnRH
      release with a variety of drugs were successful only in the presence of prazosin,
      an antagonist to alpha 1-adrenergic receptors. One possible explanation for this
      muscarinically mediated stimulation of GnRH release is that it results from cross
      talk between the muscarinic and the alpha 1-adrenergic receptors, i.e.,
      muscarinic agonists might inhibit the release induced by alpha 1-agonists, and
      muscarinic antagonists, by cancelling this inhibitory effect, might thus allow
      the endogenous alpha 1-agent, norepinephrine, to induce the release of GnRH.

PMID- 1363789
TI  - Distribution of glutamate-like and glutamine-like immunoreactivities in the rat
      organ of Corti: a light microscopic and semiquantitative electron microscopic
      analysis with a note on the localization of aspartate.
AB  - The light- and electron microscopic localization of glutamate and glutamine in
      the rat organ of Corti was studied by means of antisera raised against the
      respective amino acids coupled to carrier proteins. The light microscopic
      analysis was performed in semithin sections treated according to the peroxidase
      antiperoxidase procedure. The two amino acids were visualized in the same
      ultrathin sections by use of postembedding immunocytochemistry with two different
      gold particle sizes. The distribution of aspartate-like immunoreactivity was also
      recorded, but only at the light microscopic level. In the hair cells, the level
      of glutamate-like immunoreactivity was higher than that in supporting cells but
      lower than that in the presumed glutamatergic terminals of cerebellar parallel
      and mossy fibres. The latter types of terminal were sampled from ultrathin
      sections that had been incubated under the same conditions as the cochlear
      sections. Within the hair cells, gold particles signalling glutamate were
      enriched on mitochondria but not on clusters of synaptic vesicles. Glutamine-like
      immunoreactivity was present in hair cells as well as supporting cells. The
      glutamate/glutamine ratio, expressed as the ratio between the respective gold
      particle densities, was considerably lower for hair cells compared with the
      cerebellar excitatory terminals. No consistent difference was found between outer
      and inner hair cells in relation to the levels and subcellular distribution of
      glutamate and glutamine immunoreactivities. Aspartate-like immunoreactivity was
      accumulated in outer hair cells, with some labelling also of border cells and
      Bottcher cells. While the present study confirmed the presence of glutamate in
      hair cells and demonstrated that these cells are also endowed with the important
      glutamate precursor glutamine, it revealed notable differences between hair cells
      and presumed glutamatergic terminals in the CNS. These could reflect differences
      in the synthesis and compartmentation of transmitter glutamate. Methodological
      factors could also contribute. Alternatively, the differences could be
      interpreted to suggest that the hair cell transmitter is not glutamate, but a
      similar compound. Aspartate could be a candidate in the case of the outer hair
      cells.

PMID- 1363794
TI  - Recent progress in bladder and kidney cancer. Proceedings of the 1st
      International Congress of the Dutch Urological Association. Rotterdam, The
      Netherlands, October 9-13, 1991.

PMID- 1363792
TI  - [Clinical assessment of a group of children with juvenile rheumatoid arthritis
      receiving long-term treatment with oral gold salt].
AB  - The authors assess the efficacy of gold salt treatment for juvenile rheumatoid
      arthritis. The study was carried out on 16 children suffering from mono
      pauciarticular, polyarticular and systemic arthritis. Treatment consisted of the
      administration of auranofin alone in a group of 8 children and auranofin
      associated to corticosteroids in a second group of 8 children. A marked
      improvement in clinical conditions was observed with slight transitory side
      effects at follow-up after 12 and 24 months.

PMID- 1363795
TI  - Reaction patterns of tumor infiltrating lymphocytes in different renal cell
      carcinomas and oncocytomas.
AB  - 1. Only clear cell and chromophilic carcinomas of the kidney exhibit a
      considerable lymphocytic infiltration which is compatible with some immunological
      responsiveness. Chromophobic carcinomas and benign oncocytomas seem to be
      immunologically reactive. This reflects the different antigen spectrum and
      histogenesis of these tumors (Storkel and Jacobi, 1989). Clear cell and
      chromophilic carcinomas are derived from the proximal tubule and chromophobic
      carcinomas and oncocytomas from the collecting duct. 2. The tumor periphery seems
      to be the place of greatest immunological importance, as basic requirements of a
      sufficient lymphocyte/tumor cell interaction can only be expected there. If these
      data are taken into account for a therapeutical approach with biological immune
      modifiers the size of the tumor (tumor burden) and proliferation index must be
      considered too. This might be a likely explanation for the positive effect of
      inhaled interleukin-2 on lung metastasis in renal cell cancers. Harvesting of
      tumor infiltrating lymphocytes for therapeutical purposes should take these
      findings into account. 3. In spite of dense lymphocytic infiltration only 3% of
      the tumor infiltrating lymphocytes exhibit the activation marker CD 25. There
      seems to be a sufficient T cell locomotion in renal cell carcinomas but an
      insufficient T-cell activation. Whether this fact is induced by lacking cytokine
      stimulation of involved lymphocytes or by still unknown mediators of the tumor
      cells is not yet known and needs further investigation. 4. Clear cell carcinomas
      exhibit most adhesion molecules and the highest amount of infiltrating cytotoxic
      T-cells and natural killer cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363793
TI  - [Effect of intra- and extrasomatic factors on the mucociliary transport].

PMID- 1363797
TI  - Proceedings of the Third International Society of Ocular Toxicology Congress.
      November 15-19, 1992.

PMID- 1363796
TI  - [Need of risk reevaluation in morphine dependence in pain patients].
AB  - It is commonly recognized than opioids analgesics have an major place in the
      treatment of pain. In spite of guidelines, opioids drugs remain underutilized in
      chronic cancer pain and acute severe pain. Among the possible factors, involved
      in the insufficient use of opioids drugs, is the fear (opiophoby) of physicians,
      nurses, patients and family to induce or to maintain an addiction. This review
      examines the potential of iatrogenic addiction. We will examined the place of
      morphine-like drugs in the treatment of severe acute pain and chronic cancer
      pain, the definition of dependency in pain patients, the assessment of the
      dependency potential in patients treated for pain. Available studies indicate
      that iatrogenic addiction is quite scarce and that the risk for a major tolerance
      is very small. Further studies will be necessary, since opioids analgesics may
      also be useful in some non-cancer chronic pain.

PMID- 1363798
TI  - The potential ocular phototoxicity of antidepressant drugs.
AB  - Light Therapy is a new treatment for patients with Seasonal Affective Disorder
      (SAD), a depressive state occurring during the winter as a result of decreased
      sunlight. The treatment involves placing the patient in front of a light box (2
      10,000 lux) for approximately 30 min to 1 hour per day during the winter months.
      Although there have been no reports of damage to the eye from this treatment with
      light alone there is increased risk in light damage to the lens and retina if
      these depressed patients are being treated with antidepressant/neuroleptic drugs
      concurrently with their light therapy. As we have been previously reported
      certain drugs, having absorptions longer than 295 nm can act as photosensitizers
      resulting in enhanced light damage to the eye. Using a screening method developed
      by Roberts, we examined the potential phototoxicity of a variety of
      antidepressant and neuroleptic drugs.

PMID- 1363799
TI  - [Clinical and experimental study of qing wen oral liquid in the treatment of
      viral infectious fever].
AB  - 110 cases of viral fever patients receiving Qing Wen oral liquid were observed.
      The total effective rate was 94.5% in comparing to 86.5% in the control group, P
      < 0.01. The shortening of time concerning both the beginning on the declining of
      fever and normalization of body temperature were obvious in comparison with the
      control. The remedy was also effective in improving symptoms and signs,
      alleviating renal failure, improving microcirculation and providing bi
      directional regulation to the immune system, thus the progression of the disease
      was controlled. Animal experiments showed that Qing Wen oral liquid could protect
      the rabbits with hemorrhagic fever, delay the incubation period and the peak of
      fever, lower the febrile index and PGE content, improve the hemorheology and
      enhance the cell-mediated immunity in CSF.

PMID- 1363800
TI  - [10th Annual Academic Meeting of the Founding of Acute Abdomen Society, Chinese
      Association of the Integration of Traditional and Western Medicine].

PMID- 1363801
TI  - Molecular dissection of the Prader-Willi/Angelman syndrome region (15q11-13) by
      YAC cloning and FISH analysis.
AB  - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental
      retardation disorders associated with deletions of proximal 15q (q11-q13) of
      different parental origin. Yeast artificial chromosome (YAC) clones were isolated
      for 9 previously mapped DNA probes from this region, and for one newly derived
      marker, LS6-1 (D15S113). A YAC contig of 1-1.5 Mb encompassing four markers
      (ML34, IR4-3R, PW71, and TD189-1) was constructed. Multi-color fluorescence in
      situ hybridization (FISH) analysis of interphase nuclei was combined with YAC
      contig information to provide the following order of markers: cen-IR39-ML34-IR4
      3R-PW71-TD189-1-LS6++ +-1-TD3-21-GABRB3-IR10-1-CMW1-tel. FISH analysis was
      performed on 8 cases of PWS and 3 cases of AS, including 5 patients with normal
      karyotypes. All eleven patients were deleted for YACs in the interval from IR4-3R
      to GABRB3. On the proximal side of the deletion interval, 10/10 breakpoints fell
      within a single ML34 YAC of 370 kb. On the distal side, 8/9 breakpoints fell
      within a single IR10-1 YAC of 200 kb. These results indicate a striking
      consistency in the location of the proximal and distal breakpoints in PWS and AS
      patients. FISH analysis on a previously reported case of familial AS confirmed a
      submicroscopic deletion including YACs corresponding to LS6-1, TD3-21 and GABRB3
      and supports the separation of the PWS and AS critical regions. Since these three
      YACs do not overlap each other, the minimum size of the AS critical region is >
      or = 650 kb.

PMID- 1363803
TI  - Dinucleotide repeat polymorphism at the RBP3 locus in chromosome band 10q11.2.

PMID- 1363802
TI  - Deletion in the prion protein gene in a demented patient.

PMID- 1363804
TI  - TaqI and Bsu36I polymorphisms in the human glycoprotein Ib alpha gene (GPIB
      alpha).

PMID- 1363805
TI  - Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene.
AB  - Medium chain acyl-CoA dehydrogenase (MCAD) catalyzes the first reaction of the
      beta-oxidation cycle for 4-10-carbon fatty acids. MCAD deficiency is one of the
      most frequent inborn metabolic disorders in populations of northwestern European
      origin. In the compilation of data from a worldwide study of 172 unrelated
      patients each representing an independent pedigree, a total of 8 different
      mutations have been identified. Among them, a single prevalent mutation, 985A-
      >G, was found in 90% of 344 variant alleles. 985A-->G causes glutamate
      substitution for lysine-304 in the mature MCAD subunit, which causes impairment
      of tetramer assembly and instability of the protein. Three of 7 rarer mutations
      have been identified in a few unrelated patients, while the remaining 4 have each
      been found in only a single pedigree. In addition to tabulating the mutations,
      the acyl-CoA dehydrogenase gene family, the structure of the MCAD gene and the
      evolution of 985A-->G mutation are briefly discussed.

PMID- 1363807
TI  - 3rd International Conference on Systemic Lupus Erythematosus. London, 13-15 April
      1992. Abstracts.

PMID- 1363806
TI  - Antinuclear antibody profile in Italian patients with connective tissue diseases.
AB  - In the present work we report data on the specificity of antinuclear antibodies
      (ANA) in a large series of Italian patients suffering from a broad spectrum of
      connective tissue diseases (CTD), by using a series of homogeneous and validated
      techniques. The present study confirms, on the one hand, generally accepted
      concepts, i.e. that certain autoantibodies are strictly associated to certain
      disease states (such as anti-PCNA and anti-Sm in systemic lupus erythematosus, Jo
      1 in polymyositis, and ACA and Scl-70 in scleroderma); the presence of 'marker'
      antibodies is, however, restricted to a relative minority of CTD patients. The
      application of a new methodological approach that considers the entire profile of
      ANA can greatly augment their diagnostic relevance and may provide useful
      indications for their interpretation, allowing us to establish for the first time
      the diagnostic usefulness not only of marker autoantibodies but also of certain
      associations between non-marker autoantibodies. Finally, the application of a
      more appropriate and powerful statistical tool (multiple correspondence analysis)
      has further emphasized the clear relationship existing between antibody
      specificities and certain disease states.

PMID- 1363808
TI  - Monoallelic expression of the human H19 gene.
AB  - Monoallelic expression of several genes has been observed in mice in which
      transcripts from parental homologues are distinguishable, but this phenomenon has
      not been demonstrated in humans. One monoallelically expressed murine gene, H19,
      encodes an abundant fetal RNA. We have found restriction site polymorphisms in
      the human H19 gene, located on chromosome 11p15, and examined the representation
      of these polymorphisms in cDNAs from fetal organs. Expression of H19 is largely
      or exclusively from a single allele; a similar analysis of the WT1 gene, on
      11p13, shows biallelic expression. In the context of previous studies of 11p15
      allelic losses in human embryonal tumours, our findings support the possibility
      of single-step inactivation of monoallelically expressed growth-regulating genes
      in human oncogenesis.

PMID- 1363809
TI  - Linkage of the Indiana kindred of Gerstmann-Straussler-Scheinker disease to the
      prion protein gene.
AB  - The Indiana kindred variant of Gerstmann-Straussler-Scheinker disease has amyloid
      plaques that contain prion protein (PrP), but is atypical because neurofibrillary
      tangles like those of Alzheimer disease are present. To map the position of the
      disease causing gene, we used three markers for linkage analyses. A missense
      mutation at codon 198 of the PrP gene (PRNP) is found in all definitely affected
      individuals and yields a maximum lod score of 6.37 (theta = 0). The disease also
      is concordant with the two other PRNP-region markers. These results demonstrate
      tight linkage of the disease-causing gene to PRNP and support the hypothesis that
      the codon 198 mutation is the cause of IK-GSS. Our studies also suggest that
      methionine/valine heterozygotes at PRNP codon 129 have a later age of onset of
      the disease than codon 129 valine/valine homozygotes.

PMID- 1363810
TI  - Mutant prion proteins in Gerstmann-Straussler-Scheinker disease with
      neurofibrillary tangles.
AB  - Two families with Gerstmann-Straussler-Scheinker disease (GSS) are atypical in
      possessing neocortical neurofibrillary tangles (NFTs), which are few or absent in
      other kindreds with GSS, in addition to amyloid plaques that react with prion
      protein (PrP) antibodies and protease-resistant PrP accumulation in the brain. A
      leucine substitution at PrP codon 102 has been genetically linked to GSS in some
      families. We examined the PrP gene in these families. A serine for phenylalanine
      substitution was found at codon 198 in the Indiana patients; arginine for
      glutamine substitution at codon 217 in the Swedish patients. These mutations in
      PrP are the first to be associated with the appearance of both PrP amyloid
      plaques and neocortical NFTs in GSS patients.

PMID- 1363811
TI  - Framing beta-amyloid.

PMID- 1363813
TI  - Cosegregation of blood pressure with angiotensin converting enzyme and atrial
      natriuretic peptide receptor genes using Dahl salt-sensitive rats.
AB  - We have evaluated the genes for angiotensin converting enzyme (ACE) and guanylyl
      cyclase A/atrial natriuretic peptide receptor (GCA) for genetic effects on blood
      pressure response to high salt diet. In F2 rats derived from Milan normotensive
      and Dahl salt-hypertension sensitive (S) rats, both ACE and GCA cosegregated with
      blood pressure, and rats that were homozygous for the S allele at both the ACE
      and GCA loci had inordinately high blood pressure. In F2 derived from Wistar
      Kyoto (WKY) and S rats, GCA revealed positive cosegregation with blood pressure,
      but ACE did not. We conclude that certain alleles at the GCA and ACE loci (or at
      loci closely linked to them) have a significant genetic impact on blood pressure
      response to high salt in specific rat strains.

PMID- 1363812
TI  - Congenital adrenal hyperplasia due to point mutations in the type II 3 beta
      hydroxysteroid dehydrogenase gene.
AB  - Classical 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta
      HSD) deficiency is an autosomal recessive form of congenital adrenal hyperplasia
      characterized by a severe impairment of steroid biosynthesis in both the adrenals
      and the gonads. We describe the nucleotide sequence of the two highly homologous
      genes encoding 3 beta-HSD isoenzymes in three classic 3 beta-HSD deficient
      patients belonging to two apparently unrelated pedigrees. No mutation was
      detected in the type I 3 beta-HSD gene, which is mainly expressed in the placenta
      and peripheral tissues. Both nonsense and frameshift mutations, however, were
      found in the type II 3 beta-HSD gene, which is the predominant 3 beta-HSD gene
      expressed in the adrenals and gonads, thus providing the first elucidation of the
      molecular basis of this disorder.

PMID- 1363814
TI  - New motif in PBX genes.

PMID- 1363815
TI  - The human pseudoautosomal GM-CSF receptor alpha subunit gene is autosomal in
      mouse.
AB  - The gene encoding the granulocyte macrophage colony stimulating factor receptor
      alpha subunit (CSF2RA) has previously been mapped to the pseudoautosomal region
      of the human sex chromosomes. In contrast, we report that the murine locus,
      Csf2ra, maps to an autosome in the laboratory mouse. By in situ hybridization and
      genetic mapping, Csf2ra maps at telomeric band D2 of mouse chromosome 19. This
      first instance of a pseudoautosomal locus in human being autosomal in mouse,
      indicates incomplete conservation between the human and mouse X chromosomes and
      suggests that the genetic content of the pseudoautosomal region may differ
      between species of eutherian mammals due to chromosomal rearrangements.

PMID- 1363817
TI  - Heterogeneity of glutathione S-transferase enzyme and gene expression in ovarian
      carcinoma.
AB  - Expression of the three major cytosolic classes of glutathione S-transferases
      (GST; Pi, Alpha and Mu) was examined by 2D gel analysis and Western blotting of
      biopsies from 26 patients diagnosed with ovarian carcinoma. In contrast to other
      tissues, at least one 'constitutive' subunit from each of the three major
      cytosolic GST classes was expressed. In most cases, pi appeared to be the major
      form present, although levels of alpha and mu subunit expression were
      approximately equal to pi in some patients. There was no detectable effect of
      prior chemotherapy on enzyme activity. Mean transferase activity for primary
      carcinoma was 79.9 +/- 11.9 (mean +/- SEM; nmol min-1 mg-1), with three pair
      matched normal tissues showing minor decreases in transferase activity. One
      sample, in which a 32% increase in tumour enzyme activity was noted, was from a
      patient with primary disease and was associated with marked overexpression of a
      relatively basic form of alpha which was absent from the matching normal tissue,
      but present in 20% of all tumours examined. RFLP analysis of genomic tumour DNA
      using a human mu class cDNA probe indicated that at least two of the three mu
      forms (the 'constitutive' form and one other) observed in ovarian tissue were
      allelic variants, as a one-to-one correlation was observed between the presence
      of two Hind III fragments at 13.1 and 2.2 kb and expression of a second, more
      basic, variable form. This latter form was positively identified as the mu class
      subunit mu based on Southern analysis and was seen to be present in 40% of the
      samples examined. However, in the absence of mu expression, at least one other mu
      class subunit probably corresponding to GST psi, was seen to be present. Thus, at
      least in ovarian tissues, absence of the mu subunit does not necessarily imply a
      lack of ability to metabolize mu substrates, as psi has similar catalytic
      activity. A third mu subunit, probably corresponding to GST phi based on its
      relatively acidic pI, was also noted in 72% of samples examined, but has unknown
      substrate specificity. Increased expression of both alpha and mu forms may be of
      relevance to disease diagnosis and drug response.

PMID- 1363818
TI  - [Anatomy and physiology of erection. Proceedings of the 86th Congress of the
      French Association of Urology 1992].

PMID- 1363816
TI  - C1 inhibitor hinge region mutations produce dysfunction by different mechanisms.
AB  - Heterozygosity for a mutant dysfunctional C1 inhibitor protein, a member of the
      serine proteinase inhibitor (serpin) superfamily, results in type II hereditary
      angioneurotic oedema. We identified a "hinge" region mutation in C1 inhibitor
      with a Val to Glu replacement at P14 Val-432. Recombinant C1 inhibitors P10 Ala-
      >Thr and P14Val-->Glu did not form stable complexes with fluid phase C1s or
      kallikrein. The P14 Val-->Glu mutant, however, was cleaved to a 96K form by C1s,
      while the P10 Ala-->Thr mutant was not. The recombinant P10 mutant also did not
      complex with C1s, kallikrein or beta-factor Xlla-Sepharose. The two mutations,
      therefore, result in dysfunction by different mechanisms: in one (P14 Val-->Glu),
      the inhibitor is converted to a substrate, while in the other (P10 Ala-->Thr),
      interaction with target protease is blocked.

PMID- 1363820
TI  - Use of mobile phones in the behavioral treatment of driving phobias.
AB  - Results of two case studies are presented to illustrate the use of mobile phones
      with in vivo exposure treatment of refractory driving phobias. Number of miles
      driven and subjective ratings of anxiety were recorded during a baseline phase
      and 8 weeks of treatment involving a total of 24 driving practices. One subject's
      use of a mobile phone increased the number of miles driven alone, but the second
      subject made little progress and regressed following removal of the phone. These
      two cases and our experience with other patients suggest that mobile phones can
      benefit many individuals whose therapeutic progress is impeded by a fear of
      driving alone, but that phones are counterproductive for certain patients. The
      potential benefits and disadvantages of using mobile phones are discussed.

PMID- 1363819
TI  - Eye movement desensitization versus image confrontation: a single-session
      crossover study of 58 phobic subjects.
AB  - Eye movement desensitization (EMD) and a control procedure, image confrontation
      (IC) were compared in a group of 58 phobics, 31 of them arachnophobes. Subjects
      confronted disturbing images in a single-session crossover trial. Anxiety levels
      were recorded on the SUD Scale. Whenever practicable, SUDs to feared objects were
      also recorded. EMD and IC were equally effective in reducing anxiety levels.
      After 1 month, during which subjects were encouraged to use IC daily, improvement
      was maintained. Since exposure to the disturbing image is common to both methods
      it must be presumed to be the basis of change when EMD is used in cases of
      phobia.

PMID- 1363822
TI  - Changes in somatostatin-like immunoreactivity in lungs from perinatal guinea pigs
      and the effects of somatostatin-14 on lung liquid production.
AB  - Somatostatin-like immunoreactivity was measured by radioimmunoassay with a
      monoclonal antibody in lungs from perinatal guinea pigs (62 +/- 2 days of
      gestation). Fetuses delivered by Caesarean section and dissected before breathing
      showed 4748 +/- 758 pg/lung (n = 25). Fetuses allowed to breathe (neonates)
      showed marked increases in activity: 7629 +/- 1355 pg/lung (n = 12) after
      breathing 30 seconds, and 10729 +/- 1064 pg/lung (n = 6) after breathing 3
      minutes (2.3-fold increase, P < 0.005). Values then declined (5203 +/- 1050
      pg/lung (n = 9) at 30 minutes; 1458 +/- 105 pg/lung (n = 4) at 60 minutes).
      Changes were similar in pg/g wet tissue. HPLC characterized the immunoreactive
      peptides as somatostatin-14 (SS-14) and somatostatin-28 (SS-28) in both fetuses
      and neonates (n = 11). SS-28 made up only 13.7 +/- 1.7% of the activity; this
      percentage did not change with breathing. The effects of synthetic SS-14 on lung
      liquid production were investigated in in vitro lungs from 42 fetal guinea pigs.
      All 21 preparations immersed in 10(-5)-10(-7) M SS-14 during the middle hour of 3
      h incubations reduced production, often approaching zero after treatment (rates,
      ml/kg body weight per h, succeeding hours: 10(-5) M (n = 9), 3.09 +/- 0.68, 0.93
      +/- 0.39, -0.05 +/- 0.60 (fall significant during and after treatment, P < 0.025
      0.005); 10(-6) M (n = 6), 3.06 +/- 0.68, 1.29 +/- 0.58, 0.36 +/- 0.38 (P < 0.05
      0.005); 10(-7) M (n = 6), 1.96 +/- 0.66, 1.11 +/- 0.34, 0.64 +/- 0.28 (P < 0.05
      0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363821
TI  - Post-traumatic stress disorder due to devastating burns overcome by a single
      session of eye movement desensitization.
AB  - This article reports on the effective use of a single session of eye movement
      desensitization (EMD) in the treatment of an exceptionally severe case of post
      traumatic stress disorder (PTSD). The patient was the survivor of burns that left
      him with massive scarring, total deafness, bilateral amputations of the upper
      extremities above the elbow, severe contractures, and severely damaged feet and
      ankles. He had endured 8 years of intense suffering from symptoms of post
      traumatic stress disorder.

PMID- 1363823
TI  - The cellular immunology of bovine paratuberculosis: the predominant response is
      mediated by cytotoxic gamma/delta T lymphocytes which prevent CD4+ activity.
AB  - Peripheral blood T-cell subsets were obtained from an experimentally sensitized
      bovine and from nine bovines naturally infected with Mycobacterium
      paratuberculosis and tested for their ability to respond to antigen. It was
      determined that following antigen challenge, proliferative responses followed a
      biphasic pattern: an initial CD4+ proliferative response, a period of anergy, and
      a final response governed by gamma/delta T lymphocytes. The anergic phase was
      characterized by a dramatic drop in peripheral blood CD4+ cells; the nature of
      the non-responsiveness could not be determined. The anergic phase was followed by
      increased proliferative responses of non-MHC restricted gamma/delta T
      lymphocytes. Although CD4+ cells had the ability to proliferate in response to M.
      paratuberculosis antigens in the absence of gamma/delta T cells, antigen-primed
      CD4+ lymphocytes failed to incorporate [3H]-thymidine in the presence of
      gamma/delta T cells and M. paratuberculosis antigen. It was concluded that M.
      paratuberculosis-specific gamma/delta T lymphocytes have immunoregulatory
      function and exhibit cytotoxic activity against antigen-primed CD4+ helper cells.
      The data suggest that the inability of effector cell populations to prevent
      intracellular proliferation of M. paratuberculosis may be a result of cytotoxic
      killing of the T helper lymphocyte population required for macrophage activation.

PMID- 1363826
TI  - Proceedings of the Workshop on Lead: Metabolism and Bone Distribution. Upton, New
      York, April 11-12, 1991.

PMID- 1363824
TI  - Role of T cells, TNF alpha and IFN gamma in recall of immunity to oral challenge
      with virulent salmonellae in mice vaccinated with live attenuated aro- Salmonella
      vaccines.
AB  - The SL3261 Salmonella typhimurium aroA live vaccine strain confers solid
      protection against oral challenge with virulent salmonellae, immunity persisting
      long after the vaccine has been cleared from the tissues. BALB/c mice immunized
      with SL3261 and later subjected to in vivo depletion of both CD4+ and CD8+ T
      cells had impaired recall of immunity to oral challenge with the virulent S.
      typhimurium C5, with increased mortality and higher bacterial loads in the
      reticuloendothelial system (RES). Selective depletion of CD4+ cells alone
      significantly impaired resistance both 8 and 14 weeks after vaccination as
      determined by estimation of bacterial numbers in organ homogenates. Depletion of
      CD8+ cells alone had less effect on immunity when performed at 8 weeks than at 14
      weeks after immunization. Administration of anti-IFN gamma or anti-TNF alpha
      antibodies also impaired recall of immunity, exacerbating a secondary infection
      in vaccinated mice. Challenge of T cell-depleted immune mice with virulent
      salmonellae caused hepatosplenomegaly with minute grossly visible focal lesions,
      and a marked increase in the number and severity of necrotic foci in spleen,
      liver and lymph nodes. A widespread mononuclear cell infiltrate was present. The
      histopathology in anti-IFN gamma-treated mice was qualitatively similar to that
      seen in T-cell depleted mice. In contrast, in the anti-TNF alpha-treated mice
      splenomegaly was much less than in T cell-depleted mice. Granulomas were absent,
      no mononuclear infiltration was observed and there was severe necrosis; the
      lesions appeared similar to or worse than those seen in naive mice. Surprisingly,
      IFN gamma was detectable in sera of both controls and T cell-depleted mice on day
      8 of the secondary infection, as well as in sera of anti-TNF alpha-treated mice
      on day 6 of infection. The results indicate that T cells, IFN gamma and TNF alpha
      are all important in the specific recall of immunity to virulent salmonellae
      conferred by immunization with live vaccines, with the effect of T cell and IFN
      gamma depletion (marked macrophage infiltration) being qualitatively very
      different from that of TNF alpha neutralization (no mononuclear infiltrate or
      granuloma formation).

PMID- 1363825
TI  - [Current treatment of bronchial asthma].

PMID- 1363827
TI  - [The involvement of D-1 and D-2 dopamine receptors in the effects of neuroleptics
      and the pathogenesis of schizophrenia].
AB  - The authors presents the literature concerned with the role of D-1 and D-2
      dopamine receptors in the pathogenesis of schizophrenia and the effects of
      neuroleptics. The author concludes that substances which stimulate the D-1
      receptors may decrease symptoms of schizophrenia and restrain the formation of
      tardive dyskinesia, whilst blocking the D-1 receptors may act anti-psychotically
      without causing tardive dyskinesia. However, they cannot be used with people
      because of their considerable toxicity. The introduction of new generation of
      neuroleptics.

PMID- 1363829
TI  - [The activity of cholestatic enzymes in viral hepatitis B].
AB  - The examination of 5-cholestasis indicating enzymes was carried out in patients
      with viral B hepatitis. The changes in activity of such enzymes: alkaline
      phosphatase, its liver isoenzyme, gamma glutamyltranspeptidase, 5'nucleotidase,
      leucine aminopeptidase and alanine aminopeptidase were estimated as for being
      useful in discovering the states of cholestasis. Already in the first week of
      observation all examined enzymes showed the highest level of activity, only in
      the case of FZ and FW, however the difference between the patients with and
      without cholestasis were markedly static. In the following weeks the differences
      in average activities between group with and without cholestasis were present in
      the case of 5'N and LAP. The activity of GGTP and AAP were high in both groups of
      patients. And so alkaline phosphatase is the enzyme which discovers the states of
      cholestasis in viral B hepatitis quickly and markedly.

PMID- 1363830
TI  - [The theoretical and applied questions in the problem of traumatic shock (based
      on the materials of the All-Union Symposium, 21-22 March 1991, Leningrad)].

PMID- 1363828
TI  - [Sigma receptors: the key to therapeutic action or the side-effects of
      neuroleptics?].
AB  - The authors discuss psychotropic effects of phencyclidine (PCP) in the context of
      neurochemical mechanisms of schizophrenia. They concentrate on sigma receptors
      and PCP receptors and tie their activity with the dopaminergic system. The
      authors describe neuroleptic effects on sigma receptors and the therapeutic
      consequences. They include that the question whether the interaction of
      neuroleptics with sigma receptors results in therapeutic effects or rather in
      undesirable symptoms will decide about the future direction of treatment of
      schizophrenia.

PMID- 1363832
TI  - [Resistance to anticancer drugs. Some strong tendencies in current research].

PMID- 1363831
TI  - [Menadione induction of Ca2+ efflux from the mitochondria and of mediator
      secretion from the nerve endings].
AB  - It is shown that menadion increases the rate of Ca2+ efflux from mitochondria
      which decreases in the presence of ditiotreitol. Menadion at concentration of 50
      microM induces Ca2+ efflux from mitochondria and its effect on synaptic
      transmission is discussed.

PMID- 1363833
TI  - The emerging epidemic of non-Hodgkin's lymphoma: current knowledge regarding
      etiological factors.

PMID- 1363834
TI  - The role of biological markers in epidemiological research: future directions.

PMID- 1363836
TI  - Statement of Giorgio Giacomelli, executive director, United Nations International
      Drug Control Programme, at the United Nations Conference on Environment and
      Development, Rio de Janeiro, Brazil, 4 June 1992.

PMID- 1363835
TI  - Cell proliferation in rat colon measured with bromodeoxyuridine, proliferating
      cell nuclear antigen, and [3H]thymidine.
AB  - Epithelial cell proliferation was studied in the normal colonic mucosa of 5-week
      old Sprague-Dawley rats, comparing [3H]thymidine incorporation (group 1) with two
      newer proliferation markers, bromodeoxyuridine (group 2) and proliferating cell
      nuclear antigen (group 3). Microautoradiography (group 1) or immunoperoxidase
      assays (groups 2 and 3) were carried out. Cells were counted for positive
      reaction and position along 50 colonic crypt columns/animal. No significant
      differences were found in number or distribution of labeled epithelial cells in
      proliferative compartments in crypt columns of normal colonic mucosa; labeled
      cells were mainly in the lower 60% of colonic crypts. Thus, in this model,
      bromodeoxyuridine and proliferating cell nuclear antigens were comparable to
      [3H]thymidine as reliable markers of proliferating epithelial cells in rat colon.

PMID- 1363838
TI  - A new PKU mutation associated with haplotype 12.

PMID- 1363839
TI  - An RsaI polymorphism in the human serotonin receptor gene (HTR1A): detection by
      DGGE and RFLP analysis.

PMID- 1363837
TI  - A new 15 bp deletion in exon 11 of the phenylalanine hydroxylase gene in
      phenylketonuria.

PMID- 1363840
TI  - Frequency and type of dental traumas in mandibular body and condyle fractures.
AB  - Dental injuries in association with 207 mandibular fractures were evaluated from
      patient files and radiographs. It was shown that 32% of the dentulous patients
      with condylar fractures had dental injuries, approximately 3.7 traumatised teeth
      per patient, most of which were dental hard tissue injuries and situated
      typically in the maxillary molar region. Dental injuries were diagnosed in 30% in
      association with mandibular corpus fractures, approximately 3.6 traumatised teeth
      per patient, and injuries were more often dental luxations in the anterior part
      of the mandible. It was found that 143 teeth were involved in the line of
      mandibular corpus fracture of 105 patients (1.4 per patient). More than half of
      the fracture lines were diagnosed as passing the periodontal ligament.

PMID- 1363842
TI  - [The participation of the small intestine in the inhibition of gastric secretion
      induced by H2-receptor blockade].
AB  - Resection of the proximal portion of small intestine impaired the inhibition of
      spontaneous gastric secretion induced by the hystodile H2-receptors blockade in
      rats. The data obtained suggests participation of enteral mechanisms in the
      inhibition of gastric secretion.

PMID- 1363841
TI  - [The specific nature of vagus influences on the heart rhythm under the action of
      humoral regulators].
AB  - Effects of taurin, somatostatin, serotonin and noradrenaline upon the vagal
      chronotropic action and its components were studied in anesthetised cats. The
      data obtained suggests the existence of a specific transmitter link for vagal
      tonic and synchronizing effects upon cardiac rhythm.

PMID- 1363843
TI  - Histamine skin sensitivity in chronic schizophrenic smokers not responding
      favourably to neuroleptics.
AB  - Histamine, the neurotransmitter involved in both immune and allergic responses to
      stress, has been reported to affect acute and chronic schizophrenic patients
      differently in histamine skin sensitivity tests. The authors tested for histamine
      skin sensitivity patients who had been hospitalized with diagnosed schizophrenia
      for many years who had not responded favourably to conventional therapy and who
      had been consistently exposed to active and/or passive smoking. These patients
      were found to be markedly sensitive to the histamine skin test, whereas a control
      group of non-hospitalized, non-smoking, non-allergic, non-medicated, 'healthy'
      volunteers, of similar age and sex, were not sensitive to the histamine
      intracutaneous test. These findings suggest a possible screening indicator in
      respect of which patients with a diagnosis of schizophrenia will respond
      favourably or not favourably to neuroleptics.

PMID- 1363844
TI  - The peptidergic neuron. Proceedings of the 11th International Symposium on
      Neurosecretion. Amsterdam, The Netherlands, June 10-14, 1991.

PMID- 1363845
TI  - The peptidergic nervous system of coelenterates.

PMID- 1363846
TI  - Somatostatin: a putative neurotrophic factor with pleiotropic activity in the rat
      central nervous system.

PMID- 1363847
TI  - Strategies in the development of peptide antagonists.

PMID- 1363848
TI  - Signal transduction in the neurohypophyseal compartments.

PMID- 1363850
TI  - Neurotransmitter colocalization and circadian rhythms.

PMID- 1363849
TI  - Synaptic and neurotransmitter regulation of activity in mammalian hypothalamic
      magnocellular neurosecretory cells.

PMID- 1363851
TI  - Peptidergic transmitters of the suprachiasmatic nuclei and the control of
      circadian rhythmicity.

PMID- 1363853
TI  - [Asymptomatic cardiac insufficiency--therapy with ACE inhibitors. Wien, 4-5
      December 1992. Abstracts].

PMID- 1363852
TI  - [The surgical treatment of malignant tumors of the head of the pancreas and of
      the periampullary area].
AB  - Under analysis are results of pancreatoduodenal resections in 71 patients. In
      patients with mechanical jaundice lymph drainage with sorption and return of
      lymph into the vascular bed was used during the preoperative preparation.
      Occlusion of the duct system of the pancreas stump with glue KL-3 was performed
      on 62 patients, in 9 patients choledochocholecysto-anastomosis was used in order
      to improve the quality of the biliodigestive opening. A cryoprocedure on the
      nonremoved portion of the tumor was performed in 3 cases on the posterolateral
      surface of the portal vein. These measures allowed the postoperative lethality to
      be reduced up to 11.2%.

PMID- 1363854
TI  - [The effect of epidermal growth factor on the expression of erb B2/neu oncogene
      in mouse embryo fibroblast cells].
AB  - The erb B2/neu oncogene encodes a protein which sequence is closely similar to
      the epidermal growth factor receptor (EGFR). We have previously found that EGF
      can induce the expression of erb B1/EGFR gene in normal and 3H-TdR transformed
      C3H/10T1/2CL8 mouse embryo fibroblast cells i.e. NC3H10 and TC 3H10 respectively,
      but we do not know whether the neu oncogene expression can be induced by EGF. In
      this study, the effect of EGF on NC3H10 and TC3H10 has been observed by Northern
      blot analysis. The result indicated that EGF had a obvious induction effect on
      neu oncogene expression in these cells. Thus, the expression of both erbB 1/EGFR
      gene and erbB 2/neu oncogene can be induced by EGF. This result may provide a
      novel clue to the molecular mechanism of EGF action in cell nucleus.

PMID- 1363855
TI  - Health aspects of the use of beta-2 adrenergic drugs in animal production.
AB  - In the zootechnical field, there is a strong need to correlate analytical results
      with biological effects of beta-2 adrenergic agonist drugs on animal health, food
      processing and human toxicology, taking into account the peculiarity of their
      administration (long-term treatments with doses tenfold as high as the
      therapeutical ones). The opportunity to use ELISA tests to readily detect illegal
      treatments, suspected on the basis of clinical and inspective data, can allow
      appropriate preventive medicine action by monitoring the food chain during its
      early steps (in living animals). Sanitary implications will not be limited only
      to serious clinical signs confirmed by analyses, but should also lead to
      educational programmes intended for farmers, showing them the main obvious risks
      in animal production associated with beta-2 agonist side-effects.

PMID- 1363856
TI  - Improvement of nitrogen supply for L-threonine production by a recombinant strain
      of Serratia marcescens.
AB  - Serratia marcescens T-2000 was previously reported to be an L-threonine-producing
      strain that harbors the recombinant plasmid carrying the mutant-type threonine
      operon. This strain produced 55 g of L-threonine/L of the medium containing urea
      as a nitrogen source after 72 h of cultivation. In the urea-containing medium,
      transitory stop of the growth was observed during the early period of cultivation
      when the entire amount of ammonium ion formed from urea via heat decomposition
      disappeared in the medium. This indicated that the shortage of ammonium supply in
      cells might delay both the cell growth and the L-threonine production. The use of
      ammonia water as a nitrogen source for L-threonine production was therefore
      studied, because microbial cells generally assimilate this source more readily
      than urea. When ammonia water was automatically fed to the medium so as to
      maintain the pH of the medium at around 7, the growth was accelerated, and the L
      threonine production reached a maximum of 65 g/L at 48 h. Under these conditions,
      sucrose, a carbon source, was continuously fed to the medium, resulting in the
      production of 100 g of L-threonine/L at 96 h. Thus, the L-threonine production of
      the recombinant L-threonine-producing strain could be increased by devising the
      method for supply of a nitrogen source.

PMID- 1363858
TI  - 1st Asian Pacific Congress of Allergology and Immunology. Bangkok, Thailand,
      November 22-26, 1992. Abstracts.

PMID- 1363857
TI  - HIV infected patients: correlation of cutaneous disease with degree of
      immunosuppression.
AB  - The AIDS epidemic has become a world-wide health problem since the disease was
      identified ten years ago. An HIV-dermatology outpatient clinic was established at
      the Albion Street Centre in Sydney to manage patients with cutaneous
      manifestations of AIDS. This study reviews the spectrum of skin disorders seen,
      and attempts to correlate skin disease with the degree of immunosuppression as
      reflected by CD4 or T helper lymphocyte counts, whereas previous reports have
      attempted to correlate skin disease with clinical signs and symptoms. Brief
      summaries of HIV disease and the cutaneous manifestations of AIDS are given.

PMID- 1363859
TI  - Adhesion molecules on the plasma membrane of epidermal cells. IV.
      Immunolocalization of the intercellular adhesion molecule-1 (ICAM-1, CD54) on the
      cell surface of a small subpopulation of keratinocytes freshly isolated from
      normal human epidermis.
AB  - The intercellular adhesion molecule-1 (ICAM-1) is a cell membrane glycoprotein
      displaying a pivvtal role in cell-cell interactions in the immune system, and is
      a ligand for LFA-1, which is expressed on leukocytes. ICAM-1 is expressed in
      different cell types, including epithelial cells in a number of organs; the
      universal feature on all these cells is ICAM-1 induction from very low ICAM-1
      constitutive levels on unstimulated resting cells to very high ICAM-1 levels
      triggered by mediators released at sites of inflammation. Therefore, since a
      strong expression of ICAM-1 on keratinocyte (KC) surface was recently
      demonstrated in various inflammatory skin lesions, in this investigation we asked
      whether very low ICAM-1 levels might be present on the plasma membrane of
      unstimulated KC in normal skin. Crude epidermal cell suspensions, freshly
      isolated from normal human skin, were immunolabeled by anti-ICAM-1 monoclonal
      antibody and stained by two highly sensitive ultrastructural detection systems,
      namely, the immunogold (5-nm-sized particles) method and the immunogold-silver
      enhancement method. The quantitative analysis of 1000 KC scrutinized under the
      electron microscope revealed that 17.2% KC were ICAM-1-positive, although a
      density per KC section (midplane) of merely 18.92 +/- 13.02 5 nm-sized particles
      was scored (n = 100), indicating that the amounts of ICAM-1 moieties on this KC
      subset are presumably low. The ICAM-1 expression on a subset of KC in normal skin
      might account for the trafficking to and from normal epidermis of LFA-1-positive
      cells, including migrating Langerhans cells and occasional leukocytes.

PMID- 1363860
TI  - Effects of ifenprodil on the N-methyl-D-aspartate receptor ionophore complex in
      rat brain.
AB  - The effects of a cerebral anti-ischemic drug ifenprodil on the receptor ionophore
      complex of an N-methyl-D-aspartate (NMDA)-sensitive subclass of central
      excitatory amino acid receptors were examined using [3H](+)-5-methyl-10,11
      dihydro-5H-dibenzo[a,d]cyclohepten-5,10- imine (MK-801) binding in rat brain
      synaptic membrane preparations as a biochemical measure. The binding in membrane
      preparations not extensively washed was markedly inhibited not only by
      competitive NMDA antagonists such as (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1
      phosphonic, D-2-amino-5-phosphonovaleric and D-2-amino-7-phosphonoheptanoic
      acids, but also by competitive antagonists at the strychnine-insensitive glycine
      (Gly) site including 7-chlorokynurenic acid and 6,7-dichloroquinoxaline-2,3
      dione. Among several proposed ligands for alpha-adrenergic receptors tested,
      ifenprodil most potently inhibited the binding in these membrane preparations due
      to a decrease in the density of the binding sites without significantly affecting
      the affinity. Ifenprodil also inhibited the binding of [3H]N-[1-(2
      thienyl)cyclohexyl]piperidine as well as of [3H]MK-801 to open NMDA channels in a
      concentration-dependent manner at concentrations above 10 nM in membrane
      preparations extensively washed but not treated by a detergent, with a Hill
      coefficient of less than unity. Further treatment of extensively washed membrane
      preparations with a low concentration of Triton X-100 resulted in an almost
      complete abolition of [3H]MK-801 binding, and the binding was restored to the
      level found in membrane preparations not extensively washed following the
      addition of both L-glutamic acid (Glu) and Gly. Ifenprodil was effective in
      inhibiting [3H]MK-801 binding via reducing both initial association and
      dissociation rates in Triton-treated membrane preparations, irrespective of the
      presence of Glu and Gly added. The binding in Triton-treated membrane
      preparations was additionally potentiated by the polyamine spermidine in a
      concentration-dependent manner at concentrations above 10 microM in the presence
      of both Glu and Gly at maximally effective concentrations. Ifenprodil invariably
      diminished the abilities of these three stimulants to potentiate [3H]MK-801
      binding at concentrations over 1 microM in a manner that the maximal responses
      each were reduced. These results suggest that ifenprodil does not interfere with
      the NMDA receptor complex as a specific isosteric antagonist at the polyamine
      domain in contrast to the prevailing view.

PMID- 1363861
TI  - Circadian and seasonal rhythms of 5-HT receptor subtypes, membrane anisotropy and
      5-HT release in hippocampus and cortex of the rat.
AB  - Specific serotonin binding (5-HT1, 5-HT1A, and 5-HT2 subtypes) and membrane
      anisotropy were measured at 2 h intervals over a 24 h period in the hippocampus
      and cortex of Wistar WU rats, housed under a 12 h light-dark cycle, with lights
      on at 07.00. All experiments were performed both in March and December. In the
      hippocampus significant circadian rhythms could be ascertained for 5-HT1 binding
      sites in March and December while for 5-HT1A (subtype of 5-HT1) binding sites the
      circadian rhythm was only significant in March. The membrane anisotropy also
      showed significant variations only in March. Circadian rhythms were also found in
      the cortex for 5-HT1 (December) and 5-HT2 (March and December) binding sites as
      well as for the membrane anisotropy (December). A correlation was found between
      membrane anisotropy and 5-HT1 and 5-HT2 binding sites in hippocampus and cortex,
      respectively. A circadian rhythmicity was also observed for serotonin release as
      measured by in vivo voltammetry in both brain areas. The results obtained on the
      diurnal variations of serotonin receptor subtypes and serotonin release and the
      probable inverse relationship of these two parameters may be relevant in
      understanding the coupling of pre- and postsynaptic activity.

PMID- 1363862
TI  - Structure and expression of human and rat D2 dopamine receptor genes.
AB  - D2 dopamine receptor may be related with the pathogenesis of Parkinson's disease
      and schizophrenia. Furthermore, the antipsychotic drugs have high affinity for D2
      dopamine receptor. We carried out the cloning of the genomic DNA for human D2
      dopamine receptor and clarified the structure of this gene. Our isolated gene
      spans about 15 kbp and consists of seven exons interrupted by six introns.
      However, putative first exon was not yet identified. Spot blot hybridization
      analysis of cell sorter fractionated human chromosomal DNA with D2 receptor
      genomic DNA revealed the localization of this gene in the chromosome 11 fraction.
      We analyzed human genomic DNA by Southern blot hybridization with D2 dopamine
      receptor genomic DNA as a probe, but so far we could not find RFLP. Northern blot
      analyses of brain RNA of several animals and rat brain RNA after various
      treatments were carried out. Developmental changes of D2 dopamine receptor mRNA
      were observed in the rat brains.

PMID- 1363863
TI  - The amino acid substrate of bovine tyrosine hydroxylase.
AB  - Tyrosine hydroxylase catalyzes the tetrahydropterin-dependent hydroxylation of
      tyrosine to form 3,4-dihydroxyphenylalanine. Several nonphysiological aromatic
      amino acids have been examined as inhibitors and substrates for bovine adrenal
      tyrosine hydroxylase. The Ki values for para-substituted phenylalanines increase
      as the size of the substituent increases. For each A2 increase in surface area of
      the substituent, the free energy of binding becomes 50 cal more positive.
      Replacement of the phenyl ring with a pyridyl ring decreases the affinity about
      one order of magnitude. A number of these aromatic amino acids are also
      substrates for the enzyme. The KM values again increase in size with increasing
      size of the substituent, but the Vmax value is independent of the reactivity of
      the amino acid. The effect of size on binding is consistent with a tight
      interaction between the para position region of the substrate and the enzyme. The
      lack of a change in the Vmax value is consistent with the rate-limiting step in
      catalysis by bovine tyrosine hydroxylase being formation of the hydroxylating
      intermediate rather than hydroxylation of the amino acid. These results will be
      useful in designing mechanism-based inhibitors of catecholamine biosynthesis and
      establish that the mechanisms of rat and bovine tyrosine hydroxylase do not
      differ significantly.

PMID- 1363864
TI  - Localization and characterization of aminopeptidase P in bovine adrenal medulla.
AB  - Aminopeptidase P (EC 3.4.11.9) is demonstrated for the first time in the
      cytosolic fraction of chromaffin cells of the bovine adrenal medulla. The enzyme
      is inhibited by metal chelators and by sulfhydryl-reactive agents, which suggests
      that both a tightly bound metal ion and a cysteine residue are necessary for
      enzymatic activity. Aminopeptidase P might be important for the modulation of the
      biological activity of neuropeptides. Its occurrence in the adrenal chromaffin
      cells provides a useful tool for studying the function of this unique proline
      specific peptidase in neuropeptide processing and secretion.

PMID- 1363868
TI  - The search for Y chromosome polymorphism is extended to negroids.
AB  - DNA samples of Negroid and Caucasoid origin were used to screen for Y-specific
      RFLPs. A total of 7 Y chromosome probes and 13 restriction enzyme digests were
      used to examine a conservative estimate of 20000bp. No new Y-specific
      polymorphisms were revealed. The paucity of polymorphism on the Y appears to be
      unrelated to possible bottleneck effects during raciation.

PMID- 1363865
TI  - Dithiotreitol specifically inhibits metabotropic responses of glutamate and
      depolarizing agents in rat brain synaptoneurosomes.
AB  - Dithiotreitol (DTT), a sulfhydryl reducing agent inhibits in a dose-dependent
      manner the inositol phosphates (IPs) accumulation responses evoked by glutamate
      and potassium without affecting that of carbachol in rat forebrain
      synaptoneurosomes. Furthermore, DTT neither provokes a depolarization of the
      membrane, nor increases the internal calcium concentration. Depolarization and
      internal calcium rise are known to stimulate IPs production. Moreover, DTT does
      not modify the depolarizing effect and the calcium rise elicited by glutamate and
      potassium. In addition, the antioxidant compounds 2-aminoethylisothiouronium
      bromide (AET) and ascorbic acid have no effect on the basal and stimulated IPs
      accumulation. Thus, it is concluded that: (1) two distinct transduction pathways
      exist, one stimulated by glutamate and depolarizing agents and the other one by
      cholinergic agonists; (2) DTT produces its inhibition by reducing disulfide
      bridges likely at the level of proteins of the phosphoinositide transduction
      mechanism.

PMID- 1363866
TI  - Changes in content of neuroactive amino acids and acetylcholine in the rat
      hippocampus following transient forebrain ischemia.
AB  - Changes in content of selected neuroactive amino acids [glutamic acid, aspartic
      acid, glycine, gamma-aminobutyric acid (GABA) and taurine] and acetylcholine
      (ACh) in the rat hippocampus following transient forebrain ischemia were
      investigated using male Wistar rats. Rats were allowed to survive for 1 or 5 days
      following 10 or 20 min of 4-vessel occlusion, and killed by a focused microwave
      irradiation. A significant reduction in all neuroactive amino acids examined
      except GABA was noted in the hippocampus on the fifth day. One day after the 4
      vessel occlusion for 10 min, no significant effect on the content of neuroactive
      amino acids in all brain areas was observed. gamma-Aminobutyric acid content in
      the hippocampus was only significantly reduced on the fifth day after the
      occlusion for 20 min. Similarly, a significant decrease in ACh content in the
      hippocampus was observed on the fifth day after the occlusion for 20 min.
      Considering the data that a significant loss of neuronal cells in the hippocampus
      (delayed neuronal death) was detected only 5 days after the 4-vessel occlusion,
      it can be said that the alterations in the hippocampus of neuroactive amino acids
      such as glutamic acid, aspartic acid, glycine and taurine are more sensitive than
      those in GABA and ACh against cerebral ischemia. A possible correlation of these
      changes of neuroactive amino acids in the occurrence of delayed neuronal death in
      the hippocampus is also suggested.

PMID- 1363870
TI  - Dinucleotide repeat polymorphisms at the P1, HBE1 and MYH7 loci.

PMID- 1363869
TI  - Dinucleotide repeat polymorphism at the HOX 2B locus.

PMID- 1363867
TI  - Involvement of Ca2+ entry and inositol trisphosphate-induced internal Ca2+
      mobilization in muscarinic receptor-mediated catecholamine release in dog adrenal
      chromaffin cells.
AB  - Catecholamine (CA) release from adrenal medulla evoked by muscarinic receptor
      stimulation has been studied using isolated perfused adrenal gland and cultured
      chromaffin cells from dogs. Muscarine and oxotremorine (1-100 microM), and
      bethanechol (0.1-1 mM) dose-dependently stimulated CA release. Muscarine-evoked
      CA release was antagonized with M1-antagonist, pirenzepine and, to a lesser
      extent, with atropine; and was reduced either by removal of extracellular Ca2+ or
      treatment with Ca2+ channel blockers. Muscarine caused an increase of 45Ca uptake
      and 22Na uptake. Tetrodotoxin (TTX) did not affect muscarine-evoked increase of
      22Na uptake and CA release. Under the absence of extracellular Ca2+, muscarine
      stimulated a 45Ca efflux. Muscarine-induced CA release was attenuated by treating
      the cells with 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate-HCl (TMB-8)
      which blocks Ca2+ release from the intracellular store. A phospholipase C
      inhibitor, neomycin, markedly reduced muscarine-induced CA release but not
      nicotine- and high K(+)-evoked release. Cinnarizine, a Ca2+ channel blocker,
      attenuated muscarine-evoked but not caffeine-induced CA release and 45Ca efflux
      in the absence of extracellular Ca2+. Muscarine caused an increase in
      intracellular free Ca2+ concentration ([Ca2+]i) in the presence of extracellular
      Ca2+. It caused a similar increase, but to a lesser extent, in the absence of
      extracellular Ca2+. The increase of [Ca2+]i induced by muscarine without
      extracellular Ca2+ was reduced by neomycin and cinnarizine. Polymixin B and
      retinal, which reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced CA
      release, had little effect on muscarine-induced CA release. Muscarine increased
      cellular Ins(1,4,5)P3 production, and atropine inhibited this increase.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1363871
TI  - Polymorphism of the CTLA1 gene on chromosome 14.

PMID- 1363873
TI  - A two-allele PstI RFLP for the alpha-1C adrenergic receptor gene (ADRA1C).

PMID- 1363872
TI  - An EcoRI polymorphism for the glutaminyl-tRNA synthetase (QARS) gene on
      chromosome 1q.

PMID- 1363874
TI  - TaqI polymorphism at the alanine:glyoxylate aminotransferase (AGXT) gene locus.

PMID- 1363875
TI  - SAM 1.1 and JOSH 4.4: two RFLPs within the human DCC gene.

PMID- 1363876
TI  - Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha)
      gene detectable by NcoI restriction of PCR product.

PMID- 1363877
TI  - Two TaqI polymorphisms at the human PGM1 locus.

PMID- 1363878
TI  - A RsaI polymorphism in the ERCC2 locus.

PMID- 1363879
TI  - The mosaic of systemic lupus erythematosus: highlights of the Third International
      Conference on SLE 13-15 April 1992.

PMID- 1363880
TI  - The Second DNA Antibody Idiotype Workshop. London, United Kingdom, 11-12 April
      1992.

PMID- 1363881
TI  - Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular
      dystrophy.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant
      neuromuscular disorder which maps to chromosome 4qter, distal to the D4S139
      locus. The cosmid clone 13E, isolated in a search for homeobox genes, was
      subsequently mapped to 4q35, also distal to D4S139. A subclone, p13E-11, detects
      in normal individuals a polymorphic EcoRI fragment usually larger than 28
      kilobases (kb). Surprisingly, using the same probe we detected de novo DNA
      rearrangements, characterized by shorter EcoRI fragments (14-28 kb), in 5 out of
      6 new FSHD cases. In 10 Dutch families analysed, a specific shorter fragment
      between 14-28 kb cosegregates with FSHD. Both observations indicate that FSHD is
      caused by independent de novo DNA rearrangements in the EcoRI fragment detected
      by p13E-11.

PMID- 1363882
TI  - Facioscapulohumeral muscular dystrophy defect identified.

PMID- 1363883
TI  - [Interrelation of plasma volume, fluid metabolism and neurohormonal activation
      after ultrafiltration in congestive heart failure].
AB  - Ultrafiltration improves the clinical condition of patients with congestive heart
      failure (CHF) through a reduction of excessive body water. We investigated the
      relationships among intra and extravascular fluids, hemodynamics and neurohumoral
      pattern following plasma water subtraction. In 55 patients with CHF (35 in NYHA
      class IV, Group A, and 20 in NYHA class II-III, Group B), removal of 3242 +/- 201
      ml and 1741 +/- 119 ml of plasma water acutely reduced plasma volume (calculated
      from hematocrit changes) by -20.7% and -12.9% in Group A and in Group B,
      respectively. Plasma volume returned to baseline values within 48 hours. Body
      weight and ventricular filling pressures also lowered and remained so for 2 days.
      After ultrafiltration urinary output increased and norepinephrine, renin activity
      and aldosterone plasma levels decreased in Group A, while a fall of diuresis and
      a rapid rise of plasma levels of the 3 hormones were observed in Group B. Two
      days after ultrafiltration the persistence of reduced body weight with recovery
      of plasma volume indicates a shift of fluid from the extravascular to the
      intravascular compartment. The different behaviour of hemodynamics, urinary
      output and neurohumoral pattern changes observed in the 2 groups after
      ultrafiltration, suggest that in severe heart failure (Group A) the physiological
      responses to intravascular volume depletion are unsettled while are preserved in
      less severe stages of the disease (Group B).

PMID- 1363885
TI  - Down-regulation of ras and myc expression associated with mdr-1 overexpression in
      adriamycin-resistant tumor cells.
AB  - The murine melanoma tumor cells, B16-BL6, are a recognized model for experimental
      and spontaneous metastasis. B16-BL6 cells express a lower metastatic phenotype
      upon acquisition of resistance to adriamycin. Using this novel system, the role
      of ras, c-myc, and multidrug-resistant gene (mdr1) expression in the metastatic
      and drug-resistant phenotype was examined. The metastatic cells expressed a high
      level of c-Ki-ras and c-myc, whereas down-regulation of both proto-oncogenes was
      observed in the adriamycin-resistant cells. The mdr1 gene, which encodes P
      glycoprotein of the drug-resistant superfamily gene, was overexpressed in drug
      resistant melanoma cells. These results suggest that altered expression of genes
      that regulate cellular proliferation and growth may be a determinant of
      metastasis and drug sensitivity of tumor cells.

PMID- 1363884
TI  - [Effect of alpha-adrenergic receptor blockade on peripheral vasoconstriction
      induced by the cold pressor test. Evidence for functional integrity of alpha 1
      and alpha 2 adrenergic receptors in patients with congestive heart failure].
AB  - Central sympathetic stimulation results in direct vascular vasoconstriction
      mediated by activation of alpha-adrenergic receptors. However, it is unknown
      whether this vasoconstriction is mediated by alpha 1 or alpha 2-adrenoceptor
      subtypes. In patients with congestive heart failure (CHF), both circulating and
      neuronally released catecholamines produces vasoconstriction via alpha-adrenergic
      stimulation. This vasoconstriction produces detrimental hemodynamic effect in CHF
      patients since it increases right and left ventricular filling pressures and
      pulmonary and systemic vascular resistances. While the myocardial alpha 1
      adrenoceptors seems not to be down-regulated in heart failure, the functional
      integrity of vascular alpha 1 and alpha 2-adrenoceptors in CHF remains to be
      elucidated. Accordingly, the present study was designed to assess whether the
      limb vascular response to alpha 1 or alpha 2-adrenoceptor stimulation is impaired
      in patients with CHF. We studied 25 control subjects and 19 patients with CHF due
      to primary dilated cardiomyopathy. Forearm blood flow was measured by venous
      occlusion plethysmography. Sympathetic stimulation was produced by cold. The
      intraarterial pump-infusions of BHT 933 (a selective alpha 2-adrenoceptors
      agonist agent, 0.1, 1, 10 micrograms/kg/min for 5 min) produced the same
      peripheral vasoconstriction in CHF and in control subjects: 32 +/- 23.9%, 47.3 +/
      20% and 55 +/- 26.1% respectively at I, II, and III dose in CHF and 28.7 +/-
      38.6%, 36 +/- 14.5%, and 57 +/- 13.8% respectively at I, II, and III dose in
      control subjects. The dose response to BHT 933 was not different in the 2
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363886
TI  - [Observation on the early development of inoculated Brugia malayi microfilariae
      in mosquitoes].
AB  - This paper reports the early development and variation of inoculated Brugia
      malayi microfilariae in 3 groups of mosquitoes, i. e. young Anopheles sinensis,
      young Culex quinquefasciatus and old Cx. quinquefasciatus. Significant
      differences were observed among these groups. Sixty hours after inoculation, the
      percentage of normally developing filarial larvae in young An. sinensis was
      72.3%; the percentage of melanized microfilariae in young Cx. quinquefasciatus
      was 75.4% and the percentage of filarial larvae which developed abnormally or
      remained in diapause status in old Cx. quinquefasciatus was 67.1%, each being
      much higher than that in the other groups. It was suggested that the immune
      competence of the mosquitoes had influence upon the filarial development. The
      intensity of the immune response not only varied with the species, but also
      diminished with the aging of mosquitoes.

PMID- 1363888
TI  - Application of anti-seminal gamma-glutamyl transpeptidase monoclonal antibody to
      forensic science.

PMID- 1363887
TI  - Necrotising arteritis in amoebic colitis.
AB  - Massive intestinal haemorrhage rarely occurs in amoebic colitis. We report a case
      of caecal amoebic ulcer in a 61 year old diabetic male who presented with massive
      lower intestinal haemorrhage requiring blood transfusion and emergency surgical
      intervention. Histologically, trophozoites of Entamoeba histolytica were seen
      invading the wall of the submucosal arteries, causing necrotising arteritis.
      Rupture of a necrosed artery probably caused massive haemorrhage.

PMID- 1363889
TI  - Management of variceal haemorrhage.
AB  - Variceal bleeding is the most important complication of portal hypertension.
      Mortality due to the first variceal bleeding is very high (50%) and of those
      surviving a variceal bleeding episode, up to 80% may rebleed. Proper management
      of the acute variceal bleeding episode, the prevention of rebleeding and primary
      prophylaxis for variceal haemorrhage are therefore mandatory in order to improve
      the morbidity and mortality of cirrhotic patients with variceal bleeding.
      Injection sclerotherapy would be the treatment of choice for acute variceal
      bleeding. Drug treatment in the form of either a combined vasopressin
      nitroglycerin regimen or somatostatin may be used as an alternative. Patients not
      responding to these treatments should be referred for surgery. For the prevention
      of variceal rebleeding, non-selective beta-blockers should be tried first,
      reserving long-term injection sclerotherapy for patients with contraindications
      or intolerance to beta-blockers or in whom beta-blocker therapy has failed.
      Surgical rescue in the form of either shunt surgery or lever transplantation
      should be considered if either treatment fails. A new technique, transjugular
      intrahepatic portosystemic stent-shunt (TIPSS) may replace shunt surgery in the
      future. Beta-blockers is the treatment of choice for primary prophylaxis of
      variceal haemorrhage and has a role in preventing acute and chronic bleeding from
      congestive gastropathy. However, the above sequential approach from the least
      invasive to the more invasive therapeutic options may not be appropriate for all
      cirrhotic patients with variceal bleeding.

PMID- 1363891
TI  - [Cancer of the breast].
AB  - Breast cancer remains a key concern for oncologists. The possibility of tamoxifen
      treatment to prevent breast cancer in high-risk women was one of the central
      topics discussed for the 1992 ASCO edition. The rationale for the studies being
      developed in the US and Europe rests on experimental data and results of adjuvant
      hormone therapy trials. Decreased risks of cancer in the opposite breast, of
      cardiovascular disease, and of osteoporosis are effects that make tamoxifen
      extremely attractive for breast cancer prevention trials in postmenopausal women.
      In premenopausal women, however, preventive tamoxifen should be viewed with
      special caution because increased incidence of second cancers have been reported,
      although with dosages higher than those suggested for preventive therapy, and
      also because of difficulties with defining familial forms. The value of
      anthracyclines for adjuvant therapy has been demonstrated by several studies.
      Furthermore, a dose-response relationship has been reported with anthracyclines
      used as adjuvant therapy or in metastatic disease. New dose-limiting toxic
      effects, including thrombocytopenia and mucitis, develop when dosages are
      increased, with concomitant rG-CSF therapy. In patients with metastases, taxol
      seems to be a promising drug. Ongoing phase I trials seek to determine the
      optimal dosage and administration modalities for the taxol-doxorubicin
      combination.

PMID- 1363890
TI  - [How do cancers resist to chemotherapy?].
AB  - Resistance is often defined as a lack of therapeutic response. Cellular
      resistance involves a decrease in intracellular levels of the antitumor agent due
      to a variety of mechanisms. These mechanisms are active in tumors with initial
      resistance as well as in those which respond initially but fail to be completely
      destroyed by chemotherapy. Although acquired forms of resistance seem to be the
      result of selection, some studies suggest that antitumor agents may induce
      resistance. Four main mechanisms of resistance are currently being investigated:
      1) multidrug resistance, involving expression of a membrane P-glycoprotein,
      responsible for resistance to hydrophobic cationic agents; 2) detoxification of
      hydrophilic agents by the enzyme glutathione-S-transferase; 3) increased
      production of enzymes targeted by antimetabolites; 4) mutation or decreased
      synthesis of topoisomerases I and II which are the targets of very recent
      antitumor agents. New data were presented at the 1992 symposium of the American
      Association for Cancer Research; expression of P-glycoprotein is controlled by
      the mutant protein P53, the oncogene ras and differentiation agents.
      Physiological effects of this molecule are related to the chloride pump. Bone
      marrow stem cells from transgenic mice obtained by transfection of the gene MDR1
      in germ cells exhibit resistance. Many agents can reverse P-glycoprotein-related
      resistance. Results from three phase I trials with Cyclosporin A as reversion
      agent were reported. It is essential to conduct clinical trials in order to
      assess the true value of these new data which hold promise for improving the
      performance of antitumor agents.

PMID- 1363892
TI  - [Advances in lung cancer].
AB  - Sessions about lung cancer of the 28th annual meeting of ASCO approached
      especially non small cell lung cancer (NSCLC). Undoubtedly the outstanding facts
      for this pathology was first the acknowledgment of the importance of a correct
      staging system, in particular in stage IIIA for which resection is a prognostic
      factor different for tumors T3N0, T3N1 as for N2. Two important topics have been
      discussed on therapy: stage IIIA treatment, in particular neoadjuvant therapy
      before surgery, and new drugs like Navelbine, taxol, and campthotecine which
      suggest the possibility of improvements for chemotherapy of NSCLC in the next few
      years. For small cell lung cancer (SCLC), different trials were designed to
      improve dose intensity with growth factors, fractionation of therapy, autologous
      bone marrow transplantation.

PMID- 1363893
TI  - Antiamnesic properties of some neuropeptides and the involvement of
      neurotransmitters in the rats.
AB  - The effects of certain neuropeptides on electroconvulsive (ECS) shock-induced
      amnesia were studied in rats. The ECS was applied immediately after the learning
      a one-trial passive avoidance paradigm. The peptides--rat atrial natriuretic
      peptide (rANP 1-28, ANP), porcine brain natriuretic peptide (pBNP 1-32, BNP), rat
      calcitonin gene-related peptide (CGRP) and bombesin--were injected into the
      lateral brain ventricle 30 min after the ECS. In order to study the possible role
      of neurotransmitters in mediating the action of the peptides on amnesia, the
      animals were treated immediately after the ECS with, doses which themselves did
      not modify either the learning itself or the amnesic action of the ECS. All the
      above peptides attenuated the ECS-induced amnesia, but the transmitters involved
      in these actions differed. The anticonvulsive action of ANP was prevented by
      haloperidol (10 micrograms/kg i. p.), propranolol (10 mg/kg i. p.) and atropine
      (2 mg/kg i. p.). Phenoxybenzamine (2.0 mg/kg i. p.), bicuculline (1 mg/kg i. p.),
      methysergide (5 mg/kg i. p.) and naloxone (0.3 mg/kg i. p.) had no effect.
      Besides alpha-adrenergic and cholinergic receptor blockers the beta-adrenergic
      blocker propranolol was also effective in preventing the antiamnesic action of
      the BNP. As concerns the action of bombesin, only haloperidol was effective.
      Alpha- and beta-adrenergic and cholinergic receptor blockers and opiates are
      involved in the antiamnesic properties of CGRP. The results showed that, despite
      the fact that the studied, peptides attenuated the ECS-induced amnesia, different
      transmitters are involved in their action.

PMID- 1363894
TI  - Endocrine ophthalmopathy: a re-evaluation of the association with thyroid
      autoantibodies.
AB  - Autoantibodies to the three major thyroid autoantigens, the TSH-receptor (TSH-R),
      thyroid peroxidase (TPO) and thyroglobulin (TG), have been investigated in 63
      Graves' patients with severe endocrine ophthalmopathy. In agreement with other
      studies, TSH-R antibodies were detectable in 88% of patients and dominated the
      autoantibody spectrum. TPO antibodies were detectable in 60% of patients and TG
      antibodies in only 25% of patients. The prevalences, as well as the amounts, of
      all three thyroid autoantibodies were not significantly different from the values
      in 51 Graves' patients without clinically significant ophthalmopathy. However, in
      the subgroup of patients with TG antibodies, the ophthalmopathy patients
      displayed a shift towards IgG4 TG antibodies. Furthermore, in the same TG
      antibody positive subgroup, the amount of TSH-R antibody was significantly higher
      in the ophthalmopathy patients than in Graves' patients without ophthalmopathy.
      These qualitative differences in thyroid autoantibodies in patients with and
      without ophthalmopathy raise the possibility that further qualitative
      differences, such as thyroid autoantibody epitopes, may exist in patients with
      ophthalmopathy. Our observations, combined with recent evidence for the presence
      of TSH-R specific mRNA in retro-orbital tissue, suggest that it may be premature
      to dismiss the potential pathogenetic or diagnostic value of thyroid
      autoantibodies, particularly TSH-R antibodies, in Graves' ophthalmopathy.

PMID- 1363895
TI  - HLA-DR/DQ gene variation in nongoitrous autoimmune thyroiditis at the serological
      and molecular level.
AB  - The etiology of autoimmune diseases is multifactorial with genetic factors being
      an important prerequisite. There are two clinical manifestations of autoimmune
      thyroiditis: the goitrous form (Hashimoto's thyroiditis) and the atrophic
      variant, which is characterized by hypothyroidism (primary myxoedema). Different
      genetic markers were assumed to be predisposing factors for the distinct clinical
      presentation. In the present study, we determined HLA A,B,C,DR,DQ alloantigens
      serologically and HLA-DQ by gene analysis in patients with nongoitrous autoimmune
      thyroiditis and randomly chosen controls. To verify the exact classifications,
      thyroid volume (median 5.85 ml) was measured by ultrasonography. HLA-DR5 was
      found in 16 of 36 (44%) patients with nongoitrous autoimmune thyroiditis and in
      only 26 of 175 controls (15%) (Pc = 0.0018). There was a tendency towards a lower
      frequency of HLA-DR7 with 6% positivity in patients vs. 29% in controls (Pc =
      0.052). Regarding HLA-DQ, DQ7 was found in 17 of 35 patients (48%) vs. 21 of 98
      controls (21%) (Pc = 0.028) (relative risk 3.5). No other association was found
      with HLA-A,B,C and HLA-DR and -DQ. Our data indicate that the genetic
      susceptibility to autoimmune nongoitrous thyroiditis is closely associated to HLA
      DR5 and DQ7 and not distinct from goitrous disease. We conclude that factors
      other than genetic ones explain the different immunological and clinical
      manifestation of chronic lymphocytic thyroiditis.

PMID- 1363896
TI  - Polymorphism study of TCR alpha and gamma genes in insulin dependent diabetes
      mellitus (IDDM) multiplex families.
AB  - T-cell receptor (TCR) alpha and gamma genes polymorphisms were analysed by
      Restriction Fragment Length Polymorphism (RFLP) in 10 Insulin Dependent Diabetes
      Mellitus (IDDM) multiplex families. TCR alpha and gamma alleles distribution does
      not significantly differ between affected and non affected children. Furthermore
      there was no excess of C alpha or V gamma allele sharing in affected sib pairs.
      Therefore the T-cell receptor alpha and gamma chain alleles studied do not seem
      to affect IDDM susceptibility per se.

PMID- 1363900
TI  - [Re-evaluation of ultrasonographic localization in primary hyperparathyroidism
      (report of 55 cases)].
AB  - In 1983-1991, 55 cases of primary hyperparathyroidism confirmed by pathology and
      surgery were screened by ultrasonography. Its frequency was 3.5 or 7.5 MHz. The
      ultrasonographic results showed as follows. The appearance rate of the foci in
      the normal position of the parathyroid was 95%, including adenoma and
      hyperplasia; its size of pathology was bigger than that determined by US; the
      sensitivity of US was 55.3%, specificity 96.2%, accuracy 81.8%, positive
      predictive value 81.5%, and negative predictive value 86.5%. The results
      improving its level of ultrasonographic diagnosis were proved as follows. (1)
      knowing the anatomy of parathyroids, and preventing from false positive and false
      negative; (2) differentiating from primary and secondary hyperparathyroidism; (3)
      grasping the features of multiple endocrine neoplasia; (4) careful and repeated
      examination was key to early and correct diagnosis.

PMID- 1363898
TI  - X-ray structure of Glu 53 human lysozyme.
AB  - The three-dimensional structure of a modified human lysozyme (HL), Glu 53 HL, in
      which Asp 53 was replaced by Glu, has been determined at 1.77 A resolution by X
      ray analysis. The backbone structure of Glu 53 HL is essentially the same as the
      structure of wild-type HL. The root mean square difference for the superposition
      of equivalent C alpha atoms is 0.141 A. Except for the Glu 53 residue, the
      structure of the active site region is largely conserved between Glu 53 HL and
      wild-type HL. However, the hydrogen bond network differs because of the small
      shift or rotation of side chain groups. The carboxyl group of Glu 53 points to
      the carboxyl group of Glu 35 with a distance of 4.7 A between the nearest
      carboxyl oxygen atoms. A water molecule links these carboxyl groups by a hydrogen
      bond bridge. The active site structure explains well the fact that the binding
      ability for substrates does not significantly differ between Glu 53 HL and wild
      type HL. On the other hand, the positional and orientational change of the
      carboxyl group of the residue 53 caused by the mutation is considered to be
      responsible for the low catalytic activity (ca. 1%) of Glu 53 HL. The requirement
      of precise positioning for the carboxyl group suggests the possibility that the
      Glu 53 residue contributes more than a simple electrostatic stabilization of the
      intermediate in the catalysis reaction.

PMID- 1363899
TI  - [Correlation of proliferation of pancreatic cancer cells with both saturation
      index and cell membrane insulin receptors].
AB  - Exogenous epidermal growth factor (or somatostatin) can stimulate (or inhibit)
      proliferation of pancreatic cancer cells, with a corresponding decrease (or
      increase) of the saturation index of the cell membrane and up-regulation (or down
      regulation) of insulin receptor expression. By measuring the saturation index and
      insulin receptor numbers on the cell membrane it may be possible to evaluate the
      curative effects of treatment on pancreatic cancer at an early time.

PMID- 1363897
TI  - Purification and properties of the cellular prion protein from Syrian hamster
      brain.
AB  - The cellular prion protein (PrPC) is encoded by a chromosomal gene, and its
      scrapie isoform (PrPSc) features in all aspects of the prion diseases. Prior to
      the studies reported here, purification of PrPC has only been accomplished using
      immunoaffinity chromatography yielding small amounts of protein. Brain
      homogenates contain two PrPC forms designated PrPC-I and -II. These proteins were
      purified from a microsomal fraction by detergent extraction and separated by
      immobilized Cu2+ ion affinity chromatography. PrPC-II appears to be generated
      from PrPC-I by limited proteolysis of the N-terminus. Fractions enriched for PrPC
      I were purified further by cation-exchange chromatography and sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Greater than 90% of the
      final product migrated as a broad band of M(r) 33-35 kDa as judged by silver
      staining after SDS-PAGE. Digestion of PrPC-I with peptide-N-glycosidase (PNGase)
      compressed the band and shifted its mobility giving an M(r) of 27 kDa. The
      protocol described should be amenable to large-scale preparation of PrPC,
      enabling physical comparisons of PrPC and PrPSc.

PMID- 1363901
TI  - Frontiers in Reproductive Biology. Symposium in honor of Professor G.E. Lamming.
      Sutton Bonington, 12-13 July 1992.

PMID- 1363902
TI  - [Evaluation of treatments with beta-blockaders after myocardial infarction].
AB  - Beta-blockers have been used after myocardial infarction since 1965: however, it
      was not until the beginning of the 80s that the large multicentre clinical trials
      published results showing clearly their beneficial effects and leading to their
      widespread usage: betablockers significantly reduce the medium term (1 to 3
      years) risk of death (-22 to -24%), especially sudden death (-32%) and the
      frequency of recurrent infarction (-27%). The cardio-protection so obtained is
      multifactorial, essentially related to their antiarrhythmic, antiischemic and
      antihypertensive effects. It has been established that beta-blockade should be
      instituted as soon as possible in the hours following the infarct (intravenous
      relayed by oral administration) and may be useful associated with aspirin.
      Although the large scale clinical trials did not determine the optimal dosage or
      the duration for which treatment should be administered, they did show that the
      groups of high risk patients were those to benefit the most from this therapy.
      Beta-blockers are usually well tolerated. However, it must be pointed out that
      18% of patients were excluded from the two principal trials (only 25 to 30% of
      infarct patients were included) because of contraindications to beta-blockers and
      that 25 to 30% of the patients initially included had to interrupt the treatment
      because of side effects.

PMID- 1363903
TI  - [Ventricular anti-arrhythmic treatments during postinfarction].
AB  - Antiarrhythmic agents may be prescribed in the post-infarction period either as
      systematic therapy to prevent sudden death or as prophylactic treatment against
      recurrences of documented life-threatening arrhythmias. Systematic therapy or
      even the treatment of symptomatic ventricular extrasystoles by Class IC anti
      arrhythmics is associated with an increased risk, especially in patients with a
      low risk of sudden death at the outset. Betablockers are effective on symptoms:
      they are not always effective on the arrhythmia but at least they do not
      aggravate the mortality of these patients. However, for high risk patients with
      post-infarction left ventricular dysfunction, betablockers are the only drugs
      which have a proven efficacy: they should therefore be prescribed, especially
      those whose efficacy has been demonstrated, at the same dosages as those used in
      clinical trials. Preventive treatment of sustained ventricular tachycardia should
      be chosen with respect to the patient's hemodynamic status. When the ejection
      fraction is under 40%, amiodarone and betablockers are the drugs of first
      intention, with controls of their efficacy by the inability to induce or the
      slowing of the tachycardia rhythm during endocavitary electrophysiological
      studies.

PMID- 1363904
TI  - [Enzymatic and molecular studies in a case of hepato-erythropoietic porphyria.
      Homozygote form of type familial cutaneous porphyria].
AB  - BACKGROUND: Porphyrias are either hepatic or erythroid, depending on the
      principal site of the specific enzymatic defect. Homozygous uroporphyrinogen
      decarboxylase deficiency, known as hepato-erythropoietic porphyria (HEP), can
      involve several mutations. CASE REPORT: A young man, aged 20 years, had gradually
      developed photosensitivity since the age of 1 year, leading to hypertrichosis and
      sclerodermoid changes in sun-exposed areas of skin. He displayed high urinary
      uroporphyrin and 7-carboxylic porphyrins, and elevated fecal and red blood cell
      iso-coproporphyrin and coproporphyrin. Erythrocyte uroporphyrinogen decarboxylase
      activity of the patient was reduced to 18% of normal control values, while those
      of his grandmother and his half-brother were 62-65% of normal. MOLECULAR BIOLOGY:
      Amplification of the genomic DNA by PCR and hybridization with allele-specific
      oligonucleotides (ASOs) demonstrated the presence of a Gly 281-->Glu mutation in
      the patient and in his grandmother and half-brother. CONCLUSION: Enzymatic
      studies and details of the familial lineage are important for precisely
      classifying this type of porphyria. Molecular biology studies are necessary
      before considering any future gene therapy.

PMID- 1363905
TI  - Ethical concerns in AIDS, a national workshop organized by the FIAMC Bio-medical
      Ethics Centre, Bombay, 27-28 April 1991.

PMID- 1363906
TI  - Multi-drug resistance: the Seventh National Cancer Institute/European
      Organisation for Research into Treatment of Cancer (NCI/EORTC) Conference,
      Amsterdam, The Netherlands, 17-20 March 1992.

PMID- 1363907
TI  - Conference on vitamin A deficiency, Bellagio, Italy, 3-7 February 1992.

PMID- 1363908
TI  - Na+/K(+)-ATPase regulation by neurotransmitters.
AB  - A long period of experimental work has led to the conclusion that Na+/K(+)-ATPase
      is the enzymatic version of the Na+/K+ pump. This enzymatic system is in charge
      of various important cell functions. Among them cationic equilibrium and
      recovering of resting membrane potential in neurons is relevant. A tetrameric
      ensemble of peptides conform the system known as alpha and beta subunits. The
      alpha subunit is subdivided in alpha 1, alpha 2 and alpha 3, according to
      different location and properties. Regulatory factors intrinsic to the Na+/K(+)
      ATPase system are: ATP, Na+ and Mg2+ concentrations inside the cell, and K+
      outside. The enzyme activity is also regulated by extrinsic factors like some
      hormones (insulin and thyroxine). Induction of gene expression or post
      translational modifications of the preexisting pool of the enzyme are the basic
      mechanisms of regulation proposed. Other extrinsic factors that seem to regulate
      the enzyme activity are some neurotransmitters. Among them the most extensively
      studied are catecholamines, mainly norepinephrine (NE) and lately serotonin (5
      HT). The mechanism suggested for NE activation of the enzyme seems to involve
      specific receptors or a non-specific chelating action related to the catechol
      group that would relieve the inhibition by divalent cations. Another possibility
      is that NE removes an endogenous inhibitory factor present in the cytoplasm. The
      Na+/K(+)-ATPase is activated also by 5-HT. In vivo pharmacological and
      nutriological manipulations of brain 5-HT are accompanied by parallel responses
      of Na+/K(+)-ATPase activity. Serotonin agonists do activate the enzyme and
      antagonists neutralize the activation. In vitro there is a different dose
      dependent activation, according to the brain region. The mechanism involved seems
      to implicate a specific receptor system. Serotonin-Na+/K(+)-ATPase interaction in
      the rat brain is probably of functional relevance because it disappears in
      amygdaloid kindling. Also it seems to influence the ionic regulation of the
      pigment transport mechanism in crayfish photoreceptors. In relation to other
      neurotransmitters, a weak response to histamine was observed with acetylcholine,
      GABA and glutamic acid, the results were negative.

PMID- 1363909
TI  - Na+/K(+)-ATPase, its endogenous ligands and neurotransmitter release.

PMID- 1363910
TI  - Quantitative autoradiographic study of somatostatin and neurotensin binding sites
      in medulla oblongata of SIDS.
AB  - Quantitative autoradiography analysis of neurotensin (NT) and somatostatin (SS)
      binding sites was performed on coronal sections of the medulla oblongata from 2
      fetuses, 6 controls and 7 victims of Sudden Infant Death Syndrome (SIDS).
      Throughout the first postnatal year, mean SS binding site density was similar in
      controls and SIDS in all structures of the medulla oblongata. The density of
      neurotensin binding sites was significantly higher in the nucleus of tractus
      solitarius (NTS) of SIDS than in controls, but there was no significant
      differences in the other areas of the medulla oblongata. Our findings suggest an
      immature developmental pattern of increased NT binding sites the NTS of SIDS.
      This alteration may be related to an abnormal central cardiorespiratory and
      arousal control which is thought to be present in SIDS.

PMID- 1363911
TI  - Na+/K(+)-ATPase as an effector of synaptic transmission.
AB  - Evidence is presented in support of the hypothesis that transmitter monoamines
      can exert their post-synaptic effects by stimulation or inhibition of Na+/K(+)
      ATPase in neuronal or glial cell plasma membranes. Stimulation of electrogenic
      sodium pumping, causing a hyperpolarization with an increase in membrane
      resistance, could account for the depression of neuronal spontaneous firing and
      the signal/noise enhancing actions of these amines. Conversely, inhibition of an
      electrogenic sodium pump in neuronal plasma membranes would lead to
      depolarization and enhanced excitability.

PMID- 1363913
TI  - Purified chaperonin 60 (groEL) interacts with the nonnative states of a multitude
      of Escherichia coli proteins.
AB  - In vitro experiments employing the soluble proteins from Escherichia coli reveal
      that about half of them, in their unfolded or partially folded states, but not in
      their native states, can form stable binary complexes with chaperonin 60 (groEL).
      These complexes can be isolated by gel filtration chromatography and are
      efficiently discharged upon the addition of Mg.ATP. Binary complex formation is
      substantially reduced if chaperonin 60 is presaturated with Rubisco-I, the
      folding intermediate of Rubisco, but not with native Rubisco. Binary complex
      formation is also reduced if the transient species that interact with chaperonin
      60 are permitted to progress to more stable states. This implies that the
      structural elements or motifs that are recognized by chaperonin 60 and that are
      responsible for binary complex formation are only present or accessible in the
      unfolded states of proteins or in certain intermediates along their respective
      folding pathways. Given the high-affinity binding that we have observed in the
      present study and the normal cellular abundance of chaperonin 60, we suspect that
      the folding of most proteins in E. coli does not occur in free solution
      spontaneously, but instead takes place while they are associated with molecular
      chaperones.

PMID- 1363912
TI  - Time-resolved fluorescence studies of tryptophan mutants of Escherichia coli
      glutamine synthetase: conformational analysis of intermediates and transition
      state complexes.
AB  - Single tryptophan-containing mutants of low adenylylation state Escherichia coli
      glutamine synthetase have been studied by frequency-domain fluorescence
      spectroscopy in the presence of various substrates and inhibitors. At pH 6.5, the
      Mn-bound wild-type enzyme (wild type has two tryptophans/subunit) and the mutant
      enzymes exhibit heterogeneous fluorescence decay kinetics; the individual
      tryptophans are adequately described by a triple exponential decay scheme. The
      recovered lifetime values are 5.9 ns, 2.6 ns, and 0.4 ns for Trp-57 and 5.8 ns,
      2.3 ns, and 0.4 ns for Trp-158. These values are nearly identical to the
      previously reported results at pH 7.5 (Atkins, W.M., Stayton, P.S., &
      Villafranca, J.J., 1991, Biochemistry 30, 3406-3416). In addition, Trp-57 and Trp
      158 both exhibit an ATP-induced increase in the relative fraction of the long
      lifetime component, whereas only Trp-57 is affected by this ligand at pH 7.5. The
      transition-state analogue L-methionine-(R,S)-sulfoximine (MSOX) causes a dramatic
      increase in the fractional intensity of the long lifetime component of Trp-158.
      This ligand has no effect on the W158S mutant protein and causes a small increase
      in the fractional intensity of the long lifetime component of the W158F mutant
      protein. Addition of glutamate to the ATP complex, which affords the gamma
      glutamylphosphate-ADP complex, results in the presence of new lifetime components
      at 7, 3.2, and 0.5 ns for Trp-158, but has no effect on Trp-57. Similar results
      were obtained when ATP was added to the MSOX complex; Trp-57 exhibits
      heterogeneous fluorescence decay with lifetimes of 7, 3.5, and 0.8 ns. Decay
      kinetics of Trp-158 are best fit to a nearly homogeneous decay with a lifetime of
      5.5 ns in the MSOX-ATP inactivated complex. These results provide a model for the
      sequence of structural and dynamic changes that take place at the Trp-57 loop and
      the central loop (Trp-158) during several intermediate stages of catalysis.

PMID- 1363914
TI  - Renaturation of citrate synthase: influence of denaturant and folding assistants.
AB  - Citrate synthase (CS), which has been denatured in either guanidine hydrochloride
      (GdnHCl) or urea can be assisted in its renaturation in a variety of ways. The
      addition of each of the assistants--bovine serum albumin (BSA), oxaloacetate
      (OAA), and glycerol--promotes renaturation. In combination, the effect of these
      substances is additive with respect to the yield of folded CS. The report of
      Buchner et al. (Buchner, J., Schmidt, M., Fuchs, M., Jaenicke, R., Rudolph, R.,
      Schmid, F.X., & Kiefhaber, T., 1991, Biochemistry 30, 1586-1591) that refolding
      of CS is facilitated by the GroE system (an Escherichia coli chaperonin [cpn]
      that is composed of GroEL [cpn60] and GroES [cpn10]) has been confirmed. However,
      we observed substantially higher yield of reactivated CS, 82%, and almost no
      reactivation in the absence of GroES, < 5%, whereas Buchner et al. reported 28%
      and 16%, respectively. In addition, we find that GroE-assisted refolding is more
      efficient for CS denatured in GdnHCl than for CS denatured in urea. This result
      is discussed in light of the known difference in the denatured states generated
      in GdnHCl and urea. Because GroEL inhibits the BSA/glycerol/OAA-assisted
      refolding, this system will be useful in future studies on the mechanism of GroE
      facilitated refolding.

PMID- 1363915
TI  - Theory of chaperonin action: inertial model for enhancement of prokaryotic
      Rubisco assembly.
AB  - We have performed a computational simulation of the aggregation and chaperonin
      dependent reconstitution of dimeric prokaryotic ribulose bisphosphate
      carboxylase/oxygenase (Rubisco), based on the data of P. Goloubinoff et al.
      (1989, Nature 342, 884-889) and P. V. Viitanen et al. (1990, Biochemistry 29,
      5665-5671). The aggregation is simulated by a set of 12 differential equations
      representing the aggregation of the Rubisco folding intermediate, Rubisco-I, with
      itself and with aggregates of Rubisco-I, leading up to dodecamers. Four rate
      constants, applying to forward or reverse steps in the aggregation process, were
      included. Optimal values for these constants were determined using the ellipsoid
      algorithm as implemented by one of us (Ecker, J.G. & Kupferschmid, M., 1988,
      Introduction to Operations Research, Wiley, New York, pp. 315-322). Intensive
      exploration of simpler aggregation models did not identify an alternative that
      could simulate the data as well as this one. The activity of the chaperonin in
      this system was simulated by using this aggregation model, combined with a model
      similar to that proposed by Goloubinoff et al. (1989). The model assumes that the
      chaperonin can bind the folding intermediate rapidly, and that the chaperonin
      complex releases the Rubisco molecule slowly, permitting time for its spontaneous
      folding while interacting with the chaperonin. This is followed by self
      association of the folded Rubisco monomer to yield the active dimeric Rubisco. A
      modification of the model that simulates temperature effects was also
      constructed. The most important results we obtained indicate that the chaperonin
      dependent reconstitution of Rubisco can be simulated adequately without invoking
      any catalysis of folding by the chaperonin. In addition, the simulations predict
      values for the association rate constant of Rubisco-I with the chaperonin, and
      other variables, that are subject to experimental verification.

PMID- 1363916
TI  - Scar formation in the cardiac conduction system of a patient with Takayasu's
      arteritis.
AB  - An autopsied case of Takayasu's arteritis associated with complete
      atrioventricular (AV) block is described for the first time. The findings of scar
      formation and diffuse infiltration of lymphocytes into the cardiac conduction
      system, particularly the AV node, were similar to those in patients with
      connective tissue diseases or congenital complete heart block. The degree of AV
      block progressed with aggravation of the disease. These findings suggest that
      complete AV block may have been induced by acquired autoimmunity involving the
      cardiac conduction system.

PMID- 1363918
TI  - Principles and methods of medicamentous protection of myocardial cellular
      membranes for prevention of cardiac reperfusion syndrome.
AB  - A model of regional transitory coronary insufficiency was employed in experiments
      on 300 male albino rats under urethan anaesthesia (13.4 mmol/kg b.m.). The
      periods of myocardial ischaemia lasted 10, 40 and 120 min, followed by
      reperfusion lasting 40 min. The alteration of cellular membrane apparatus proved
      to be one of the most important mechanisms responsible for myocardial lesion
      during transitory coronarogenic ischaemia and for the development of cardiac
      reperfusion syndrome. The damage to cardiomyocyte membrane and intensity of
      reperfusion syndrome can be substantially reduced by using the following
      measures: inhibition of lipoperoxidation by antioxidative preparations, esp.
      myofedrin and verapamil; suppression of the intensity of phospholipase reactions
      activated by Ca2+; reduction of calcium ion accumulation in cardiomyocytes by
      substances lowering intracellular calcium content, esp. by verapamil.

PMID- 1363919
TI  - Primary and secondary changes in the brains of suckling Balb/c mice with
      experimental hemorrhagic fever.
AB  - To testify whether primary changes caused by the virus with its related factors
      and secondary changes caused by hypotension in the brains of patient with
      epidemic hemorrhagic fever (EHF) could be repeated in the animal model, suckling
      Balb/c mice were inoculated IP with 100 LD50/0.05 ml of Chen strain of
      hemorrhagic fever virus. After the onset of the disease, paraformaldehyde and
      glutaraldehyde were used for fixation by perfusion through left ventricle.
      Sections stained with HE and MAb against EHF virus by immunocytochemical method
      (4-step PAP) showed diffuse viral antigen deposition. All brains were diffusely
      scattered with single cell acidophilic necrosis which are believed to be caused
      primarily by the virus. 33.3% of the brains also showed symmetrical distribution
      of cerebral infarct-like necrosis which are believed to be caused secondarily by
      hypotension. This result supports our previous study on the autopsy of brains of
      EHF patients.

PMID- 1363917
TI  - Transglutaminase changes in intestinal mucosa after experimental small bowel
      resection in the rat.
AB  - The low serum transglutaminase found in various intestinal disorders (celiac
      disease and IBD) suggested to us to study the serum and mucosal transglutaminase
      behaviour in an experimental model of small intestine resection in rats to reduce
      cellular mass and induce enterocyte hyperproliferation in the proximal part left
      in continuity. Transglutaminase activity in the intestinal mucosa was
      significantly higher in resected rats than in control and sham operated animals
      from days 4 (121 +/- 10 v basal 94 +/- 3 mU/g protein, p < 0.01) to 10 (165 +/-
      37 mU/g protein, p < 0.05) after surgery; no significant difference was observed
      at days 12 and 15 (110 +/- 15 and 105 +/- 23 respectively). Both serum alkaline
      phosphatase activity (partly produced in enterocytes) and serum transglutaminase
      were significantly lower in resected rats at each time-point beginning at day 6
      (208 +/- 34 v 557 +/- 125 UI and 1.55 +/- 0.11 v 3.78 +/- 0.70 mU/ml, p < 0.001
      respectively). These data suggest an involvement of transglutaminase in
      enterocyte proliferation and confirm the association between reduced intestinal
      mass and low levels of the enzyme in serum.

PMID- 1363920
TI  - [Susceptibility of thirty-one species of mosquitoes to Romanomermis yunanensis].
AB  - A new species of Mermithidae was found parasitizing the larvae of Culex
      tritaeniorhynchus and Culex fatigans in Henan, China and then named Romanomermis
      yunanensis. Thirty-one species of Mosquitoes involving six genera have been
      tested for susceptibility to R. yunanensis and Culicinae mosquito have
      consistently been highly susceptible. At a 1:5 ratio of mosquito larvae to
      nematode juveniles, the parasitisms of Aedes aegypti, Ae. albopictus, Culex
      fatigans, Culex tritaeniorhynchus, Anopheles sinensts, Psorophora columbiae and
      Culesta inornata were 98.2%, 98.5%, 98.6%, 97.1%, 0%, 98.8%, and 99.0%
      respectively. R. yunanensis presented a phenomenon of retarted development in
      Anopheles maculatus, which remained at the parasitic stage both in the larvae and
      pupa of An. maculatus. The parasitism of An. dirus was 89.7%, but most (88.8%)
      parasitizing mermithids underwent melanization and died. The comparative
      susceptibility of some North American mosquitoes to R. yunanesis and R.
      culicivorax at a 1:5 infective ratio showed that both percentage infection and
      intensity of infection statistically supported the generalization that, under
      laboratory conditions, R. yunanesis is a more vigorous and aggressive parasite of
      Culicinae.

PMID- 1363921
TI  - 6th European Congress on Intensive Care Medicine. Barcelona, Spain, October 27
      31, 1992. Abstracts.

PMID- 1363923
TI  - Effects of thienodiazepine derivatives, etizolam and clotiazepam on the
      appearance of Fm theta.
AB  - The effects of new thienodiazepine anxiolytics, etizolam and clotiazepam, on the
      appearance of frontal midline theta activity (Fm theta) were studied by the
      double-blind crossover method. The results were as follows; 1) Both clotiazepam
      and placebo tended to increase the Fm theta appearance in all subjects, but
      etizolam showed no such tendency. 2) Clotiazepam significantly increased the Fm
      theta appearance as compared with placebo in subjects with a high neurotic
      tendency (N-scale of MPI above 19). 3) Clotiazepam tended to increase the Fm
      theta appearance as compared with placebo and etizolam in subjects with a high
      anxiety level (MAS score above 14). 4) Apparently more subjects complained of
      drowsiness after the administration of etizolam than after clotiazepam or
      placebo.

PMID- 1363924
TI  - Proceedings for the 17th Meeting of The Japanese Society of Sleep Research.
      Fukui, June 5-6, 1992. Abstracts.

PMID- 1363922
TI  - Effects of casein and soy-protein on alpha-linolenic acid metabolism in rats.
AB  - In order to study the effects of different proteins on alpha-linolenic acid
      (alpha-LnA) metabolism, rats were given the diet added respectively with milk
      casein and soy-protein isolate (SPI) as sources of proteins and perilla oil as a
      source of lipid. The results obtained are as follows. The ratio of (C20:3 +
      C20:4)/C18:2 in liver microsomal PL, liver PE fraction, and kidney PE and PC
      fractions was significantly lowered by the SPI treatment when compared to the
      casein treatment, similarly to the already established results. In the liver
      microsomal PL and PE and PC fractions of liver and kidney in rats treated with
      SPI, there was also observed a significant decrease or a decrease tendency in the
      (C20:4 + C20:5)/C18:3 ratio. A similar tendency was again shown in the sigma (n
      3)M/C18:3 ratio indicating metabolic conversion from C18:3(n-3) to C22:6. On the
      other hand, contrary to the ratios of (C20:3 + C20:4)/C18:2, sigma (n-3)M/C18:3,
      and (C20:3 + C20:5)/C18:3, the (C22:5 + C22:6)/C20:5 ratio which is the parameter
      for metabolic conversion of C20:5(n-3) was elevated in the PE and PC fraction of
      liver, heart and kidney in the SPI group compared to the casein group. Then,
      further analysis of the metabolic process from C20:5 to C22:6 showed that the
      C22:5/C20:5 ratio increased while the C22:6/C22:5 ratio decreased in the SPI
      group compared to the casein group. Based on these results, it is assumed that
      the metabolic process from C18:3(n-3) to C20:5(n-3) and from C22:5 to C22:6 is
      affected by SPI but that the elongation process from C20:5(n-3) to C22:5(n-3), on
      the contrary, is rather accelerated by SPI.

PMID- 1363925
TI  - (-)Deprenyl (selegiline) is devoid of amphetamine-like behavioural effects in
      rats.
AB  - Central effects of high dose (-)deprenyl (50-100 mg/kg sc) was compared to that
      of (+)deprenyl and (+/-)amphetamine (AM). (+)Deprenyl and AM induced stereotyped
      behaviour, increased spontaneous motility in smaller and decreased it in higher
      doses, inhibited escape behaviour and shuttle-box avoidance. (-)Deprenyl failed
      to possess any of these effects, providing further evidence that AM-type
      metabolites have no share in the action of (-)deprenyl.

PMID- 1363926
TI  - Regulation of protein kinase C after stimulation of alpha 1-adrenoceptors in rat
      hippocampus.
AB  - Endogenous inhibitor of protein kinases (type II inhibitor, GABA-modulin) blocks
      the phosphorylation catalyzed by cAMP-dependent protein kinase (PKA) and protein
      kinase C (PKC) as a competitive inhibitor of substrate proteins when histone is
      used as a substrate. Moreover, type II inhibitor blocks the phosphorylation of
      endogenous membrane proteins by PKC. Stimulation of alpha 1-adrenoceptors induced
      rapid redistribution of PKC from cytosol to membrane fraction which lasted at
      least 3 h, accompanied by rapid and short-lasting translocation of type II
      inhibitor from membrane to cytosol fraction. The cytosol content of type II
      inhibitor reached maximal level 10 and 20 min and became normal again 40 min
      after i.p. administration of methoxamine. The above actions of methoxamine were
      completely blocked by pretreatment with prazosin. It seems that short-lasting
      redistribution of type II inhibitor from membrane to cytosol fraction allows the
      effective phosphorylation of membrane proteins by PKC after stimulation of alpha
      1-adrenoceptors.

PMID- 1363927
TI  - Cross reactivity among the ligands of the 7 helix family.
AB  - "Specific" drugs for receptors of the 7 helix family inhibited in high doses
      other receptors of the same family, as well. Atropine inhibited [3-H]-clonidine
      binding, beta-adrenergic drugs: propranolol, betoxalol, ICI 118.551 inhibited
      labelled QNB binding to all the 3 main subtypes of muscarinic receptors. Authors
      propose the existence of common features in the ligand binding sites of the
      receptors of 7 helix family.

PMID- 1363928
TI  - Anxiolytic profile of girisopam and GYKI 52,322 (EGIS 6775). Comparison with
      chlordiazepoxide and buspirone.
AB  - The anxiolytic action of two 2,3-benzodiazepines: girisopam: GYKI 51,189 (EGIS
      5810): (1-(3-chlorophenyl)-4-methyl-7,8-dimethoxy-5H-2,3-benzodiazepine), and
      GYKI 52,322 (EGIS 6775): (1-(4-aminophenyl)-4-methyl-7,8-dimethoxy-5H-2,3
      benzodiazepine) was investigated in comparison to chlordiazepoxide and buspirone
      using three different animal models of anxiety: the lick conflict, the elevated
      plus maze and the open field methods in rats. Both 2,3-benzodiazepines exerted
      anxiolytic effect in all three tests used, however their pharmacological profile
      differs considerably from that of either chlordiazepoxide or buspirone. Using the
      animal models mentioned above the order of potency was GYKI 52,322 (EGIS 6775) >
      chlordiazepoxide > girisopam > buspirone.

PMID- 1363929
TI  - Inhibition of hippocampal field potentials by GYKI 52466 in vitro and in vivo.
AB  - GYKI 52466 is a specific antagonist of the neuronal excitation mediated by the
      non-NMDA type excitatory amino acid receptors, at several sites in the central
      nervous system. The experiments presented here show that the drug has a dose
      dependent, slowly developing, long-lasting and reversible inhibitory action on
      the field potentials recorded from the CA1 region of the rat hippocampus, in
      vitro. Its action is similar to that of the well-known non-NMDA receptor blocker,
      CNQX. When the stimulus intensity-dependence of the population spikes was
      investigated, both drugs shifted the input-output curves in a parallel manner,
      while the maximum responses were only slightly depressed at the doses applied.
      With i.v. application, GYKI 52466 also inhibited the hippocampal field potentials
      recorded from the CA1 region of anesthetized rats dose-dependently. The
      inhibition was relatively weak compared to the effect found in earlier studies in
      the spinal cord, by the same doses. Four mg/kg i.v., a doses which is able to
      block spinal reflexes completely, caused an only about 20% depression of the
      recorded responses in the hippocampal CA1 area.

PMID- 1363930
TI  - The excitatory effects of opioids.

PMID- 1363932
TI  - Steric and hydrophobic determinants of the solubilities of recombinant sickle
      cell hemoglobins.
AB  - Models for the structure of the fibers of deoxy sickle cell hemoglobin (Hb Hb S,
      beta 6 Glu-->Val) have been obtained from X-ray and electron microscopic studies.
      Recent molecular dynamics calculations of polymer formation give new insights on
      the various specific interactions between monomers. Site-directed mutagenesis
      with expression of the Hb S beta subunits in Escherichia coli provides the
      experimental tools to test these models. For Hb S, the beta 6 Val residue is
      intimately involved in a specific lateral contact, at the donor site, that
      interacts with the acceptor site of an adjacent molecule composed predominantly
      of the hydrophobic residues Phe 85 and Leu 88. Comparing natural and artificial
      mutants indicates that the solubility of deoxyHb decreases in relation to the
      surface hydrophobicity of the residue at the beta 6 position with Ile > Val >
      Ala. We also tested the role of the stereospecific adjustment between the donor
      and acceptor sites by substituting Trp for Glu at the beta 6 location. Among
      these hydrophobic substitutions and under our experimental conditions, only Val
      and Ile were observed to induce polymer formation. The interactions for the Ala
      mutant are too weak whereas a Trp residue inhibits aggregation through steric
      hindrance at the acceptor site of the lateral contact. Increasing the
      hydrophobicity at the axial contact between tetramers of the same strand also
      contributes to the stability of the double strand. This is demonstrated by
      associating the beta 23 Val-->Ile mutation at the axial contact with either the
      beta 6 Glu-->Val or beta 6 Glu-->Ile substitution in the same beta
      subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1363931
TI  - Gln-41 is intermolecularly cross-linked to Lys-113 in F-actin by N-(4
      azidobenzoyl)-putrescine.
AB  - The bifunctional reagent N-(4-azidobenzoyl)-putrescine was synthesized and
      covalently bound to rabbit skeletal muscle actin. The incorporation was mediated
      by guinea pig liver transglutaminase under conditions similar to those described
      by Takashi (1988, Biochemistry 27, 938-943); up to 0.5 M/M were incorporated into
      G-actin, whereas F-actin was refractory to incorporation. Peptide fractionation
      showed that at least 90% of the label was bound to Gln-41. The labeled G-actin
      was polymerized, and irradiation of the F-actin led to covalent intermolecular
      cross-linking. A cross-linked peptide complex was isolated from a tryptic digest
      of the cross-linked actin in which digestion was limited to arginine; sequence
      analysis as well as mass spectrometry indicated that the linked peptides
      contained residues 40-62 and residues 96-116, and that the actual cross-link was
      between Gln-41 and Lys-113. Thus the gamma-carboxyl group of Gln-41 must be
      within 10.7 A of the side chain (probably the amino group) of Lys-113 in an
      adjacent actin monomer. In the atomic model for F-actin proposed by Holmes et al.
      (1990, Nature 347, 44-49), the alpha-carbons of these residues in adjacent
      monomers along the two-start helices are sufficiently close to permit cross
      linking of their side chains, and, pending atomic resolution of the side chains,
      the results presented here seem to support the proposed model.

PMID- 1363933
TI  - Isolation and characterization of porcine somatotropin containing a succinimide
      residue in place of aspartate129.
AB  - Aspartate129 in porcine somatotropin was converted into a cyclic imide residue
      (succinimide) under acidic solution conditions. Reversed-phase high performance
      liquid chromatography was utilized to isolate and quantitate this altered
      species, which accounted for approximately 30% of the total protein. The
      molecular mass of this modified species was determined by electrospray mass
      spectrometry to be 18 Da less than normal porcine somatotropin, indicative of a
      loss of 1 H2O molecule. Tryptic peptide mapping demonstrated that the peptide
      composed of residues 126-133 was altered in this modified protein. Amino acid
      analysis, amino acid sequencing, mass spectrometry, and capillary zone
      electrophoresis were used to demonstrate that aspartate129 in this peptide had
      been converted into a succinimide residue. Further confirmation that this peptide
      contained a succinimide was obtained by hydrolyzing the modified peptide at pH
      9.0, which yielded both the aspartate and isoaspartate peptides.

PMID- 1363934
TI  - A series of point mutations reveal interactions between the calcium-binding sites
      of calmodulin.
AB  - Calmodulin is a member of the "EF-hand" family of Ca(2+)-binding proteins. It
      consists of two homologous globular domains, each containing two helix-loop-helix
      Ca(2+)-binding sites. To examine the contribution of individual Ca(2+)-binding
      sites to the Ca(2+)-binding properties of CaM, a series of four site-directed
      mutants has been studied. In each, the glutamic acid at position 12 in one of the
      four Ca(2+)-binding loops has been changed to a glutamine. One-dimensional 1H-NMR
      has been used to monitor Ca(2+)-induced changes in the mutant proteins, and the
      spectral changes observed for each mutant have been compared to those for wild
      type CaM. In this way, the effect of each mutation on both the mutated site and
      the other Ca(2+)-binding sites has been examined. The mutation of glutamate to
      glutamine at position 12 in any of the EF-hand Ca(2+)-binding loops greatly
      decreases the Ca(2+)-binding affinity at that site, yet differs in the overall
      effects on Ca2+ binding depending on which of the four sites is mutated. When the
      mutation is in site I, there is only a small decrease in the apparent Ca(2+)
      binding affinity of site II, and vice versa. Mutation in either site III or IV
      results in a large decrease in the apparent Ca(2+)-binding affinities of the
      partner C-terminal site. In both the N- and C-terminal domains, evidence for
      altered conformational effects in the partners of mutated sites is presented. In
      the C-terminus, the conformational consequences of mutating site III or site IV
      are strikingly different.

PMID- 1363936
TI  - [Neurological manifestation of Takayasu's arteritis].
AB  - 38 cases of Takayasu's arteritis were reported. The mean age of onset was 23.3
      years with a female: male ratio of 1:1.7. The median delay between first symptom
      and time of diagnosis was 12.2 years. Headache was the most common symptom of
      neurologic manifestations (55%). Major neurologic events occurred in 52.7%
      patients in this group, including TIA, cerebral infarction, hypertensive
      encephalopathy, lacunar infarct, seizure, paraplegia, watershed infarct, cerebral
      hemorrhage, Moyamoya phenomenon, and confusion in the order of frequency. A
      variety of mechanisms that must be taken into account in explaining this
      neurologic events were proposed. The secondary hypertension and cardiac
      complications play an important role in causing neurologic symptoms. The
      formation of anastomotic networks has "Jekyll and Hyde" effect on brain both in
      preventing or limiting the ischemic injury and in producing some special symptoms
      and signs, that further widen the clinical spectrum of brain involvement.

PMID- 1363935
TI  - Electrostatic interactions in the association of proteins: an analysis of the
      thrombin-hirudin complex.
AB  - The role of electrostatic interactions in stabilization of the thrombin-hirudin
      complex has been investigated by means of two macroscopic approaches: the
      modified Tanford-Kirkwood model and the finite-difference method for numerical
      solution of the Poisson-Boltzmann equations. The electrostatic potentials around
      the thrombin and hirudin molecules were asymmetric and complementary, and it is
      suggested that these fields influence the initial orientation in the process of
      the complex formation. The change of the electrostatic binding energy due to
      mutation of acidic residues in hirudin has been calculated and compared with
      experimentally determined changes in binding energy. In general, the change in
      electrostatic binding energy for a particular mutation calculated by the modified
      Tanford-Kirkwood approach agreed well with the experimentally observed change.
      The finite-difference approach tended to overestimate changes in binding energy
      when the mutated residues were involved in short-range electrostatic
      interactions. Decreases in binding energy caused by mutations of amino acids that
      do not make any direct ionic interactions (e.g., Glu 61 and Glu 62 of hirudin)
      can be explained in terms of the interaction of these charges with the positive
      electrostatic potential of thrombin. Differences between the calculated and
      observed changes in binding energy are discussed in terms of the crystal
      structure of the thrombin-hirudin complex.

PMID- 1363937
TI  - [Main drug interactions at a hospital emergency department. Analysis of 100
      cases].
AB  - We prospectively reviewed clinical charts of 100 consecutive patients that were
      admitted during the first trimester 1991 to the Emergency Department of a general
      hospital in order to determine the more frequent prescribed drugs and their
      interactions using a computer program (Drug Interaction Program), emphasizing in
      those drugs used to treat peptic ulcers. Number of drugs prescribed to each
      patient was 4.20 +/- 1.39. Antacids (39%) and cimetidine (35%) occupied the third
      and fourth place. There were interactions in 79 patients and in 66 of them (84%)
      they were important. Antacid and cimetidine were similarly prescribed, but of 35
      patients who received cimetidine only 3 (8.5%) had a primary indication for its
      use (Gastrointestinal bleeding). Significant clinical interactions of cimetidine
      with other medications are analyzed. Our results indicate that drug interactions
      are a permanent risk in our hospitals. We suggest to use a computer program on
      drug interactions or an updated chart of medications in the emergency rooms of
      our hospitals.

PMID- 1363938
TI  - Restriction endonuclease digestion patterns of harvest mice (Reithrodontomys)
      chromosomes: a comparison to G-bands, C-bands, and in situ hybridization.
AB  - Constitutive heterochromatin of a karyotypically conserved species of harvest
      mouse was compared to that of three karyotypically derived species of harvest
      mice by examining banding patterns produced on metaphase patterns produced by two
      of these restriction endonucleases (EcoRI and MboI) were compared to published G-
      and C-banded karyotypes and in situ hybridization of a satellite DNA repeat for
      these taxa. The third restriction endonuclease (PstI) did not produce a
      detectable pattern of digestion. For the most part, patterns produced by EcoRI
      and MboI can be related to C-banded chromosomes and in situ hybridization of
      satellite DNA sequences. Moreover, digestion with EcoRI reveals bands not
      apparent with these other techniques, suggesting that restriction endonuclease
      digestion of metaphase chromosomes may provide additional insight into the
      structure and organization of metaphase chromosomes. The patterns produced by
      restriction endonuclease digestion are compatible with the chromosomal evolution
      of these taxa, documenting that in the highly derived taxa not only are the
      chromosomes rearranged but the abundance of certain sequences is highly variable.
      However, technical variation and difficulty in producing consistent results even
      on a single slide with some restriction endonucleases documents the problems
      associated with this method.

PMID- 1363939
TI  - Fixed implant-supported prostheses with welded titanium frameworks.
AB  - Eighty-six edentulous patients provided with Branemark implants were randomly
      selected for fixed prostheses with modified framework designs. This study
      describes alternative laboratory techniques in which premachined titanium
      components are welded together to form the framework. Clinical experience,
      following the patients for 1 year after placement, indicates that it is a
      predictable technique with a similar pattern of complications as experienced by
      patients with cast frameworks supported by implants. The prostheses are
      considered to be slightly more bulky than cast frameworks, but seem to have, on a
      clinical level, a better fit to the implants.

PMID- 1363940
TI  - International workshop: Vaccines for Peace--an international program for the
      development and use of vaccines against dual-threat agents. 9-14 September 1992,
      Biesenthal, Germany.

PMID- 1363941
TI  - [The absence of reproducible effects from anxiolytics and anxiogens on the
      behavior of different strains of mice in a dark-light chamber].
AB  - Experiments on 1,200 male mice (150 groups) of three strains (SHR bred from
      Swiss, C57BL/6 and CC57BR) were made during 4 years (1986-1989) to test five
      anxiolytics (diazepam, phenazepam, chlordiazepoxide, phenibut, buspiron) and
      ethanol, three anxiogens (pentylenetetrazol, caffeine, yohimbine) and three
      putative endogenous anxiogens (beta-phenylethylamine, kynurenine and quinolinic
      acid) using a dark-light chamber. None of the drugs administered within a wide
      dose range produced any stable reproducible effect on the number of transitions
      between two compartments or on the dark preference. Thus, the reported data on an
      increase in the number of transitions induced by benzodiazepine anxiolytics were
      not confirmed. The data obtained demonstrate that the dark-light chamber is not a
      reliable system for simulating anxiety in mice.

PMID- 1363942
TI  - [A hypothesis of the possible mechanism of the action of analgesic agents at the
      neuronal level].
AB  - The opiate analgetic promedol and non-opiate analgetics analgin, clonidine,
      baclofen, tolibut, vasopressin and calcitonin given in adequate doses block the
      inward electrosensitive sodium transmembrane ionic current of neurons. Like some
      drugs which do not exhibit any analgetic effect, promedol, analgin, clonidine,
      vasopressin and calcitonin also block the electrosensitive delayed potassium
      current. It is assumed that the blocking of the sodium ionic current may be one
      of the potential analgetic mechanisms at the neuronal level.

PMID- 1363943
TI  - [The withdrawal syndrome and lipid peroxidation during the chronic administration
      of narcotic analgesics to rats].
AB  - Diverse behavioral disorders and the intensity of lipid peroxidation (LPO) of
      biological membranes were estimated in different rat tissues after the 7-day
      administration and subsequent withdrawal of morphine or promedol. 24 hours after
      the withdrawal of the analgetics the demonstrated a high initial level of motor
      activity in the open field. Naloxone, an antagonist of opiate receptors,
      potentiated motor activity and the intensity of withdrawal syndrome (by 160%) in
      rats with morphine rather than promedol dependence. The behavioral disorders in
      dependent animals were accompanied by LPO activation in liver and brain
      membranes.

PMID- 1363944
TI  - [The current status and prospects of drug treatment in mental diseases].

PMID- 1363946
TI  - The Role of Bacteria and Viruses in Bronchial Asthma and Other Allergic Diseases.
      International symposium proceedings. Zakopane, March 19-22, 1991.

PMID- 1363945
TI  - [The effect of propranolol and flusoxolol on the lysosomal enzyme activity of the
      rat ventricular myocardium].
AB  - The nonselective beta-blocker propranolol and the selective beta 1-adrenoblocker
      flusoxolol were tested for their effects on the activities of acid phosphatase,
      acid DNAase, cathepsin D, beta-glucosidase and beta-galactosidase in intact rat
      ventricular myocardial homogenates. The two drugs were found to have the most
      noticeable effect on the activity of three enzymes under study: acid phosphatase,
      beta-glucosidase and beta-galactosidase. They were able to stabilize lysosomal
      membranes during long-term homogenate preincubation at 37 degrees S. It is
      suggested that the mechanism of action of the drugs on intact rat ventricular
      myocardial lysosomes under the conditions of the study involves the binding of
      both propranolol and flusoxolol to beta-adrenoceptors on the lysosomes.

PMID- 1363947
TI  - [Neurobiology of memory].
AB  - A first part of the paper describes the neuro-anatomical structures involved in
      the processes of memory and their connections, as demonstrated by the recent
      hodological methods. The classical view of the Papez's limbic circuitry
      represents only one part of the reality. Several other circuits do exist,
      including those relaying in the amygdaloid complex and in the septal area.
      Actually, all these structures can be understood as the nodal points of a set of
      cortico-subcortical networks, where information is distributed and processed
      according to the cognitive demand and finally stored in the cortical layers. In a
      second part, the various mechanisms at the cellular level in relation with the
      processes of learning, are discussed (i.e. plasticity of synaptic transmission,
      dynamic neuronal changes at the morphological, electrophysiological and metabolic
      levels). The role played by humoral neuromodulation is examined, although it
      remains largely unknown at present (i.e. acetylcholine, catecholamines, GABA,
      glutamate, neuropeptides). Unfortunately, therapeutical implications from these
      fundamental data stay mostly frustrating up to now. Finally, relationships
      between sleep and memory are considered. The abundant experimental work performed
      on animals mainly stresses the REM-sleep. However, data from the human pathology
      are much less conclusive, and no clear evidence of a specific interaction between
      one aspect of sleep and one kind of memory emerges. To conclude, a few remarks
      are warranted on the intimal links existing between the anatomical-functional set
      of memory and the neurobiological bases of behavioural responses and anticipatory
      processes.

PMID- 1363948
TI  - [Memory disorders in schizophrenia].
AB  - The current interest in memory disorders in schizophrenia results from the way
      perceptions of schizophrenia--whose organic origin is becoming increasingly
      evident--and memory--according to which there exist not one, but several memories
      -have developed. Memory disorders in the schizophrenic cannot be considered in
      isolation from knowledge accumulated in other areas of the cognitive and neuro
      sciences; a more detailed understanding of these disorders requires a comparison
      of the different cognitive approaches, both with each other and with the
      neurobiological and clinical approaches, so that they can be integrated. Despite
      numerous methodological and conceptual difficulties, it now appears to have been
      established that the schizophrenic's memory deficit should be seen in the context
      of a wider cognitive deficit, that the memory tasks are not all disturbed and
      that the memory deficit cannot be identified with one specific form of memory.
      Thus, iconic formation, short-term memory in the traditionally accepted sense and
      implicit memory are hardly, if at all, affected; in contrast, the early
      processing of information, working memory and explicit memory are disturbed,
      probably to the extent that they require the implementation of strategies to
      organise the information to be memorized. Finally, in certain tasks, such as
      those evaluating latent inhibition or negative priming, schizophrenics perform
      better than normal subjects, suggesting that schizophrenics' cognitive deficit is
      localised. This profile of memory disorders is compatible with a dysfunction
      predominating in the frontal and temporo-hippocampal regions. Neuroleptics and
      anticholinergics have opposite effects on cognitive and mnesic performance, which
      is improved by the former and aggravated by the latter. The influence of clinical
      symptoms, positive or negative, institutionalisation of patients and chronic
      tardive dyskinesia is unclear. Among the theoretical proposals put forward to
      account for the observed disorders, those relating to a disturbance of the action
      planning process and to that of the internal representation of context are
      compatible with the observed memory disorders. All the clinically derived data
      and those produced by the cognitive and neurosciences indicate a need to
      reformulate the links between memory, selective attention and evaluation of the
      relevance of a stimulus, to develop a general model of the reciprocal
      interactions between cognition and affectivity and to look for the origin of a
      pathology as complex as schizophrenia, not in a local lesion in an isolated
      cerebral structure but in a disturbance of the dynamic interactions within a
      functional, parallel and distributed network of broadly interconnected regions.

PMID- 1363949
TI  - 33rd Annual Conference of the Indian Society of Gastroenterology in association
      with Society of Gastrointestinal Endoscopy and Indian Association for the Study
      of Liver. New Delhi, November 6-8, 1992. Abstracts.

PMID- 1363951
TI  - 48th Annual Conference of the Association of Physicians of India. New Delhi,
      January 20-24, 1993. Abstracts.

PMID- 1363950
TI  - Paraventricular nucleus-pineal interaction: relevance to tardive dyskinesia.

PMID- 1363952
TI  - [XV Annual Meeting of the French Society of Rheumatology and the V French
      Congress of Rheumatology. Paris, 27-29 November 1992. Abstracts].

PMID- 1363953
TI  - Quality assurance of immunophenotyping.

PMID- 1363954
TI  - Symposium on the Health and Management of Free-Ranging Mammals. Proceedings.

PMID- 1363955
TI  - [The pharmacological regulation of neutrophil activity by cholinotropic
      preparations, barbiturates and fenazepam].
AB  - The in vitro experiments with human blood cells and in vivo experiments on Wistar
      rats have demonstrated that stimulation of neutrophils enhances their phagocytic
      metabolic activity. Barbiturates (benzonal and phenobarbital) and phenazepam in
      low concentrations (doses) increase neutrophilic function evaluated by the NBT
      test, but in high ones cause opposite effects.

PMID- 1363956
TI  - [The GABA-ergic component of the anxiolytic action of 1-(2-pyrimidinyl)
      piperazine derivatives].
AB  - The 1-(2-pyrimidinyl)-piperazine derivatives campirone, campironine,
      levopironine) evoked hyperpolarizing responses of rat dorsal root ganglion
      neurons mediated by 5-hydroxytryptamine(1A) receptor activation and, like
      chlordiazepoxide, potentiated neuronal responses evoked by GABA-depolarizing
      receptor activation. The drugs studied in the lighted space and threatening
      situation avoidance tests showed an anxiolytic effect. Picrotoxin was found to be
      effective in inhibiting the anxiolytic effect of chlordiazepoxide, levopironine
      and campironine, but it failed to affect the antianxious action of campirone.
      Whether the GABA-ergic mechanisms may contribute to the anxiolytic action of 1-(2
      pyrimidinyl)-piperazine derivatives.

PMID- 1363957
TI  - [The role of the genotype in the cataleptogenic effect of neuroleptics].
AB  - The cataleptogenic effects of three neuroleptics from one chemical group was
      investigated in 8 mice strains (CBA, A/He, C57B1/6, C3H/He, BALB/c, AKR, DD, and
      CC57Br. Despite significant interstrain, differences in the action of the drugs,
      haloperidol (0.5 mg/kg) and trifluperidol (0.5 mg/kg) produced much greater
      cataleptogenic action than fluspirilene (2 mg/kg). At the same time the intensity
      of catalepsy in various mice strains after haloperidol was not coincident with
      that after trifluperidol (r = 0.22): CBA mice displayed the maximum catalepsy,
      but AKR, DD and CC57Br mice, the minimum when haloperidol was given; with
      trifluperidol, the maximum catalepsy was observed in AKR mice, but absent in DD
      mice. Fluspirilene induced catalepsy only in CBA and A/He mice. Thus, the
      presence of catalepsy, a side effect of most neuroleptics, is largely
      predetermined by hereditary factors.

PMID- 1363958
TI  - [Anticancer substances of vegetable origin. Spindle poisons: vincaleukoblastine,
      leurocristine and navelbine; taxol and taxotere].
AB  - The biological activity of spindle poisons can easily be measured using an in
      vitro assay based on the interaction of these substances with their cellular
      "receptor": tubulin. The use of this assay led us to select Navelbine and
      Taxotere as antimitotic substances. These compounds, as well as their natural
      parents: vincaleucoblastine, leurocristine and taxol respectively, have been
      obtained by semi-synthesis using relatively abundant natural precursors as
      starting materials. This paper summarizes the preparation of these important
      anticancer drugs.

PMID- 1363959
TI  - [Determination of colonization factor antigens CFA in diagnosis of
      enterotoxigenic strains of Escherichia coli].
AB  - This study was aimed at establishment whether preliminary determination of
      colonization factor antigens CFA may be useful in selection of potentially
      pathogenic strains of Escherichia coli with serological types belonging to ETEC
      and 750 isolates of E. coli from children with symptoms of diarrhoea.
      Enterotoxigenicity of strains was evaluated by suckling mice test and culture of
      Y1 cell tissue. Colonization factor antigens CFA were evaluated on the basis of
      slide agglutination and agar gel immunodiffusion with application diagnostic sera
      prepared for this study. Ability of enterotoxin production was found in 25%
      strains of E. coli with serological types belonging to ETEC. In 90% these strains
      were isolated from cases of epidemic diarrhoea. ETEC strains were found in 11% of
      hospitalized children and in 5% who were treated outside of hospital because of
      diarrhoea. MRHA adhesins occurred on 80% of ETEC strains were all diagnosed as
      CFA/I. CFA/II were not found and in only three strains non-fimbrial CFA/IV was
      present. Preliminary determination of CFA during selection of ETEC strains
      presents as a very sensitive method (97%) and is also highly specific (99%).
      Application of this method will result in significant increase of affectivity of
      biological tests directed toward determination of E. coli enterotoxigenicity.

PMID- 1363960
TI  - [Occurrence of P.fimbrii in strains from selected genera of Enterobacteriaceae].
AB  - This study was aimed at recognition of frequency of occurrence of P fimbriae in
      strains of Escherichia coli isolated from samples of feces of children with
      symptoms of diarrhoea and at search of these adhesions in strains representing
      other than Escherichia genera of Enterobacteriaceae strains. One hundred forty
      laboratory strains were investigated. They belonged to genus Citrobacter,
      Enterobacter, Hafnia, Klebsiella, Morganella, Proteus, Providencia, Salmonella,
      Shigella, and Yersinia. Also were tested 1277 colonies of enteric rods isolated
      from the MacConkey's medium inoculated with samples of feces from 163 children
      with symptoms of diarrhoea. Mannose-resistant active hemagglutination test was
      performed with human group O erythrocytes and guinea pig erythrocytes stabilized
      with glutaraldehyde. Presence of P fimbriae was detected by the slide latex test
      with latex covered by P1 glycoprotein. Among 140 laboratory strains of
      Enterobacteriaceae in 21 strains (3-E. cloaceae, 2-Hafnia, 13-K. pneumoniae, 2-P.
      rettgeri and in one strains of Providencia) presence of MRHA adhesins was
      demonstrated. Nine of these strains (2-Hafnia, 5-K. pneumoniae and 2-P. rettgeri)
      reacted specifically in the latex test. Among 1142 colonies of E. coli isolated
      from children with symptoms of diarrhoea, 326 colonies belonged to 13 EPEC
      serotypes. With 118 (36.2%) of EPEC colonies a positive result of MRHA reaction
      was found with human erythrocytes and 34 (10.4%) with guinea pig erythrocytes.
      Positive latex test was obtained with 77 (23.6%) colonies. All these colonies
      possessed MRHA adhesins. Remaining 816 colonies of E. coli strains did not
      represent microorganisms belonging to serotypes accepted as enteropathogenic.
      From 112 (13.7%) colonies out of 816 not belonging to EPEC, positive results was
      obtained in the MRHA test with human erythrocytes and this was the case also with
      41 (5.0%) colonies in MRHA reaction with application of guinea pig erythrocytes.
      The latex test was positive in 65 (7.9%) colonies of E. coli. From remaining 135
      colonies other than E. coli, positive result of latex test of presence of P
      fimbriae was obtained with 54 (40.0%) colonies, including 14 colonies of E.
      cloacae, 23-K. pneumoniae and 17-K. oxytoca. In all these strains presence of
      MRHA adhesins was demonstrated. These investigations demonstrated that among EPEC
      strains significantly more frequently, than not belonging to these serotypes of
      E. coli, MRHA adhesins, including P fimbriae was observed.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1363961
TI  - [Root resorption].
AB  - Root resorption can be divided into two main categories: internal root resorption
      and external root resorption. Internal root resorption is a pathology that can
      lead to tooth destruction in the short term and must consequently be stopped as
      soon as possible by applying adequate canal treatment. Until now, despite many
      research studies, very little is known about its causes and the way this kind of
      resorption appears. There are many different forms of external root resorption
      and it has a very diverse etiology. An external root resorption can thus appear
      in case of orthodontic treatment or due to the pressure brought by cysts, tumours
      or impacted teeth. A trauma or an infection may also lead to the development of
      an external root resorption. Because they are so diverse, each of these forms of
      external root resorption requires a specific treatment. It should also be noted
      that internal root resorptions, and some forms of external resorption too, often
      respond favourably to a calcium hydroxide treatment.

PMID- 1363962
TI  - Analysis of cytogenetic damage induced in CHO cells by the pyrethroid insecticide
      fenvalerate.
AB  - A synthetic pyrethroid insecticide, fenvalerate, was tested for its ability to
      induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in CHO
      cells. Fenvalerate was assayed both in the presence and in the absence of a rat
      liver activation system (S9-mix). Our results indicate that fenvalerate in the
      presence of S9-mix is able significantly to increase the frequency of CA, while
      in the SCE test this increase occurred both in the presence and in the absence of
      S9-mix. In addition, fenvalerate affected the cell cycle, causing a decrease in
      the mitotic index (MI) and in the proliferative rate index (PRI).

PMID- 1363963
TI  - Valproic acid induced abnormal development of the central nervous system of three
      species of amphibians: implications for neural tube defects and alternative
      experimental systems.
AB  - Embryos of Ambystoma mexicanum, Xenopus laevis, and Hyperolius viridiflavus
      taeniatus were exposed to various concentrations of valproic acid (VPA: 0.1, 1.5,
      10 mM) from blastula stage (S) 9 on up to advanced gastrulation of control
      embryos (S 11 1/2-12). At 10 and 5 mM VPA early development was affected in all
      species tested. However, the most pronounced effects occurred in Ambystoma: the
      neural folds appeared delayed and showed a flattened and wavy shape; the neural
      tube was not formed and embryos successively died. In Xenopus and Hyperolius (10,
      5 mM VPA) the beginning of gastrulation was delayed up to neurulation of control
      embryos. In Xenopus many of the embryos completed neurulation, whereas some
      embryos exposed to 10 mM VPA showed neural tube defects (NTDs) of different type
      and degree (open neural tube at different regions of the dorsum). In Hyperolius
      neural folds arose around the blastoporus and fused later on (earlier in embryos
      treated with 5 mM VPA), but the shape of these embryos was abnormal and the
      development was not continued (pronounced effect at 10 mM VPA). Comparing the
      three species, Xenopus proved to be the least sensitive species (at 5 mM VPA
      14.2% NTDs of total malformations compared to 100% in the other species). The
      most sensitive species, Ambystoma, developed head-oedema at 1 mM VPA, whereas the
      anurans were not affected. Our results suggest a similar mechanism of VPA-induced
      NTDs in mammals and amphibians.

PMID- 1363964
TI  - Effect of acyl derivatives of 4,4,4-trifluoro-1-phenyl-1,3-butanedione on 2
      acetylaminofluorene-induced glutathione S-transferase positive foci in the rat
      liver.
AB  - Acyl derivatives of 4,4,4-trifluoro-1-phenyl-1,3-butanedione (TFPB), 1-benzoyl-2
      trifluoromethyl-2-acetoxyethene (BTAE), and 1-benzoyl-2-trifluoromethyl-2-(4
      methylthio)benzoyloxyethene (BTME), were synthesized and investigated for
      inhibition of tRNA binding by N-acetoxy-2-acetylaminofluorene (N-AcO-AAF), and
      induction of glutathione S-transferase placental form (GST-P) positive foci in
      the rat liver by 2-acetylaminofluorene (2-AAF). Male F344 rats were given BTAE or
      BTME intraperitoneally and 2-AAF by intragastric intubation. Two weeks following
      the treatment, the rats were maintained on the diet containing 0.05%
      phenobarbital for an additional 6 weeks and then killed. Development of GST-P
      positive foci was not affected by concomitant treatment with BTAE or BTME. These
      two compounds inhibited the in vitro binding of N-AcO-AAF to tRNA. Thus, although
      these diacylmethane derivatives had the in vitro inhibitory activity, they did
      not inhibit tumor-initiating activity of 2-AAF in the rat liver.

PMID- 1363965
TI  - Analysis of carcinogenic activity of some pesticides in a medium-term liver
      bioassay in the rat.
AB  - Eight pesticides were tested in a medium-term bioassay based upon the induction
      of preneoplastic lesions in the liver. Rats were initially given
      diethylnitrosamine intraperitoneally at a dose of 200 mg/kg body weight and 2
      weeks later were treated with the pesticides for 6 weeks and then killed; all
      rats had a partial hepatectomy at week 3. Hepatocarcinogenic potential was
      assessed by comparing the number and area of glutathione S-transferase placental
      form positive foci in the liver with those of controls given diethylnitrosamine
      (DEN) alone. Positive results were seen with p,p-DDT and Triadimefon. Permethrin
      (mixture of 39% cis form and 61% trans form) showed borderline results.
      Permethrin (25/75), Deltamethrin, Cypermethrin (52/48), while Trimorphamide and
      Propineb gave negative results. Our findings provide experimental evidence to
      indicate that compounds active in this assay have a potential for liver
      carcinogenicity in rodents.

PMID- 1363966
TI  - A morphologic basis postulated for valproic acid's embryotoxic action in rats.
AB  - A tentative 3 phase sequence of pathogenesis is proposed for the embryotoxic
      action of valproic acid (800 mg/kg) administered orally to rats on day 13 of
      pregnancy. This is based on histopathological changes in the extraembryonic and
      embryonic tissues which occurred in the absence of any biologically significant
      effect on maternal homeostasis. Major events in the first, decidual (or maternal)
      phase are cells lining the maternal sinusoids in the decidua basalis are
      necrosed, desquamated, and washed away by the arterial circulation through the
      afferent channels. The necrosed cells, with their walls still intact, occlude the
      lumen of these arterial channels at the point of their entry into the giant cell
      trophospongial zone. The channel occlusions cause ischemia and homeostasis of the
      maternal circulation in the labyrinth by reducing the rate of inflow of maternal
      blood. The embolic occlusion of maternal arterial channels apparently results in
      a long-term reduction in the number and size of maternal channels that supply
      arterial blood to the labyrinth. In the second or placental phase, the parenchyma
      of the labyrinth and connective tissue in the chorionic plate and umbilical cord,
      which have been deprived of nutrition and oxygen by the ischemia and stasis of
      maternal blood in the labyrinth, undergo degenerative changes. In the third or
      embryonic phase, a pleiotropic karyorrhexis in the embryo, initiated as early as
      4 h postdosing, appeared aggravated, presumably by the preceding labyrinthine
      degeneration of the placental phase. The valproic acid-induced embryotoxicity
      thus seemed to result from a combination of maternal, placental, and embryonic
      changes.

PMID- 1363967
TI  - Vitamins and cancer prevention.

PMID- 1363969
TI  - 2nd Nordic Toxicology Congress, NordTox-92. Symposium proceedings. Aland Islands,
      Finland, May 1992.

PMID- 1363968
TI  - International cancer epidemiology meetings.

PMID- 1363970
TI  - Effect of striatal lesion with quinolinate on the development of substantia nigra
      dopaminergic neurons: a quantitative morphological analysis.
AB  - We have previously reported that a developmental axon-sparing striatal injury
      induced by hypoxia-ischemia results in a diminished adult number of substantia
      nigra (SN) tyrosine hydroxylase (TH)-positive neurons, in the absence of direct
      nigral injury. To examine the specific role of striatal injury, we made selective
      striatal lesions in the 7-day-old rat with quinolinic acid (QA), 40, 80, 120 and
      480 nmol. Striatal lesions resulted in a decrease in the adult number of TH
      positive neurons in the ipsilateral SN. The decrease was correlated with the
      reduction in striatal area (r = 0.76, p < 0.01); a 25-30% reduction in SN neurons
      was observed at 50-60% striatal area loss. The area of SN pars compacta (SNpc) in
      animals with 120- and 480-nmol QA lesions was reduced by 12 and 15%, respectively
      (p < 0.01) and this reduction also correlated with the loss of striatal area (r =
      0.63, p < 0.01). Individual TH-positive neuron size and neuron-packing density
      were unaltered in SNpc on the experimental side. We conclude that the adult
      number of SN dopaminergic neurons depends on developmental support by the
      striatum. We hypothesize that less support by the smaller striatum may result in
      accentuated developmental cell death in the SNpc.

PMID- 1363971
TI  - Release of neurotransmitters and neurosecretory substances during in vitro
      maturation of mouse hypothalamic cultures.
AB  - The maturation of the neurosecretory activity of a hypothalamic nerve cell
      population grown in vitro, prepared from 10-day-old mice and cultured for 6 days,
      has been demonstrated in the present report. A low-molecular weight polypeptide
      of 30-kD was found to be released into the culture media during the 6-day period
      of incubation, as analyzed by SDS-polyacrylamide gel electrophoresis. Comparative
      electrophoresis of the in situ hypothalamic, neurohypophysis and cerebral cortex
      homogenates revealed the presence of a 30-kD protein component in both the
      hypothalamus and neurohypophysis but not in the cerebral cortex. The release of
      the 30-kD polypeptide into the incubation media indicates an expression of the
      neurosecretory activity of the peptidergic neurons of the hypothalamus during in
      vitro maturation. On the other hand, high pressure liquid chromatography with
      electrochemical detection showed appreciable quantities of released dopamine
      (DA), epinephrine and serotonin (5-HT) in the incubation media in which the
      neurons were allowed to differentiate. There was a steady release of DA during
      the 6-day incubation period, varying from 0.21 +/- 0.02 to 0.49 +/- 0.05 ng/mg
      protein. The epinephrine level increased progressively from day 1 to 6 of
      culture, from 3.73 +/- 0.57 to 12.08 +/- 1.81 ng/mg protein, respectively. The
      measured 5-HT level was 0.07 +/- 0.001 on day 2 and increased to 0.38 +/- 0.05
      ng/mg protein on day 6 of culture. These data demonstrate the functional
      maturation of catecholaminergic, serotoninergic and peptidergic neurons in these
      rotary histotypic cultures of the mouse hypothalamus.

PMID- 1363972
TI  - [Pulmonary vasoconstrictor responses].
AB  - Alterations in the physiological balance to maintain the pulmonary circulation at
      a normal low pressure level result in an elevation in pulmonary vascular tone.
      Pulmonary vasoconstrictor responses were analyzed under some experimental
      conditions, which included microembolism, administration of vasoactive agents,
      hypoxia, and monocrotaline-induced pulmonary hypertension. It is widely accepted
      that these responses are highly localized and complex. In the present study,
      excised canine lung lobes, rat lungs, and pulmonary arterial rings from the rat
      were employed according to the particular experimental design. The mechanism of
      the initial rapid elevation followed by a gradual decline in perfusion pressure
      in microembolism was considered to be related not only to the size of the emboli,
      but to the degree of mechanical injury of the endothelium. The main sites of
      constriction of the pulmonary vasculature by several drugs were determined in the
      pulsatile perfused canine lung lobes, according to the degree of decrease in
      inflow wave amplitude during antegrade or retrograde perfusion. Further, by
      applying the same method it was confirmed that the site of hypoxic
      vasoconstriction is located in the peripheral pulmonary vascular bed between the
      muscular arteries and veins, which are constricted mainly by serotonin and
      histamine, respectively. A cross perfusion system was set up, employing two lobes
      from the same dog, in which normoxic blood was perfused into the hypoxic
      ventilated lobe and vice versa. As a result, the pulmonary vessels showed a
      response to ventilation hypoxia that was far more sensitive than that to
      perfusion hypoxia. The effects of a beta-agonist (isoproterenol) and beta
      antagonists (propranolol, pindolol) on hypoxic vasoconstriction were observed.
      Although pindolol (a vasodilatory beta-blocker) abolished hypoxic pulmonary
      vasoconstriction, which was similar to the effect of isoproterenol, the mechanism
      of action of pindolol was suggested to be different from that of isoproterenol.
      The importance of the K+ channel of vascular smooth muscle and also the
      endothelium in hypoxic pulmonary vasoconstriction were stressed. In isolated
      pulmonary artery segments of the monocrotaline-treated rat, the augmentation of
      sensitivity of the vascular smooth muscle to Ca2+ preceded the occurrence of
      pulmonary hypertension. Similarly, hyperreactivity to KCl and serotonin was also
      observed. It was clarified that the hyperreactivity induced by monocrotaline is
      modified by endothelium-dependent relaxation. Extensive cellular and molecular
      biological investigations are essential for further progress in this field.

PMID- 1363973
TI  - [Pharmacological evidence for the existence of beta 3-adrenergic receptors in
      canine airway smooth muscle].
AB  - There is increasing evidence for the existence of a third atypical beta
      adrenergic receptor (beta 3-adrenoceptor) in various tissues including
      adipocytes, cardiac myocytes and intestinal smooth muscle preparations. In the
      present study, to determine whether beta 3-adrenoceptors also exist in the airway
      smooth muscle, we studied isolated bronchial segments from dogs under isometric
      conditions in vitro. Application of beta-adrenoceptor agonists produced a
      concentration-dependent relaxation of tissues precontracted with 10(-5) M
      acetylcholine, the order of potency being isoproterenol (1) > or = salbutamol, a
      beta 2-selective adrenoceptor agonist (0.95) > or = BRL 37344, a beta 3-selective
      adrenoceptor agonist, (0.83) >> norepinephrine (0.10). Under the condition in
      which alpha- and beta 1-adrenoceptors had been blocked by phentolamine and ICI
      89406, respectively, the relaxant response to salbutamol was competitively
      antagonized by the beta 2-adrenoceptor antagonist ICI 118551, and the pA2 value
      was 7.01 +/- 0.25 (mean +/- SE), whereas the response to BRL 37344 was resistant,
      with of apparent pA2 value of 5.66. However, cyanopindolol, an antagonist
      atypical beta-adrenoceptors, antagonized BRL 37344-induced relaxation in a
      competitive fashion with a pA2 of 6.74 +/- 0.11. This pA2 value was lower than
      that when salbutamol was used as an agonist (p < 0.05). These results indicate
      that beta 3-adrenoceptors probably exist in canine bronchial smooth muscle, and
      that stimulation of this type of receptors produces potent bronchodilation.
      Therefore, a specific agonist for beta 3-adrenoceptors could be valuable in the
      treatment of asthma.

PMID- 1363974
TI  - Human cytochrome P450IIE1 gene: DraI polymorphism and susceptibility to cancer.
AB  - Human cytochrome P450IIE1 (CYP2E) is involved in the metabolic activation of
      procarcinogens such as N-nitrosodimethylamine, benzene and ethyl carbamate. We
      screened DNA from 28 individuals for restriction fragment length polymorphisms
      (RFLPs) is the human P450IIE1 gene and detected an RFLP for the restriction
      endonuclease DraI. The distribution of the genotypes of this polymorphisms among
      lung cancer patients (n = 74) differed from that among controls (n = 73) with
      statistical significance of p < 0.05. In addition, the distribution among
      patients with cancers of the digestive system (n = 38) was also different from
      that among controls. Our findings indicate an association between the DraI
      polymorphism of the IIE1 gene and susceptibility to cancers of the lung and the
      digestive system.

PMID- 1363976
TI  - Recent Advances in Cancer Research. Proceedings of Sendai International
      Symposium. Sendai, November 14-16, 1991.

PMID- 1363975
TI  - A possible role of activated macrophages in the adoptive immunotherapy using CD4+
      T lymphocytes.
AB  - Potent anti-tumor T lymphocytes with CD4+8- phenotype were obtained in peritoneal
      exudate cells by immunizing mice with irradiated tumor cells and OK-432. These
      effector cells were used in adoptive immunotherapy for tumor-bearing mice.
      Admixed administration of effector T cells with irradiated relevant tumor cells
      resulted in a marked enhancement of anti-tumor activity against local tumor and
      lymph node metastasis compared with the immunotherapy by effectors alone. The
      activating state of macrophages inoculated with viable tumor cells had much
      relevance with the implementation of immunotherapy. Innocent bystander lysis was
      not observed in this immunotherapy. Interleukin-2 given instead of stimulant
      tumor cells caused no enhancement, while interleukin-1 emerged stronger
      enhancement than stimulant tumor. In this case, activating state of macrophages
      had no relevance with the effectiveness of the therapy. These results suggest
      that macrophages in tumor play a role to secrete interleukin-1 to enhance anti
      tumor activity of specific T cells.

PMID- 1363978
TI  - Analysis of ultrastructural changes in the myocardium of rats during withdrawal
      syndrome after gradual decreasing of metipranolol doses.
AB  - Hypersensitization of the myocardium occurring in rats after remission of
      metipranolol's beta-blocking effect in experiments manifested itself by marked
      proliferation of the mitochondrial apparatus of myocytes accompanied by an
      increase in SDH activity as well as its ultrastructural pattern return to control
      values after a shorter period of A characteristic feature of the withdrawal
      syndrome occurring in the myocardium of rats exposed to stress following
      discontinuation of premedication with metipranolol, is partial damage to the
      mitochondrial apparatus of myocytes associated with a decrease in SDH activity
      and presence of hyperactive nuclei. Based on the results obtained, the author
      concludes that, while the withdrawal syndrome sets in during gradual decrease in
      long-term metipranolol doses in the rat myocardium on stress, it lasts shorter
      than after sudden interruption of treatment, and myocardial metabolism as well as
      its ultrastructural pattern return to control values after a shorter period of
      time.

PMID- 1363977
TI  - Present status of agonistic and antagonistic analogs of LH-RH in the treatment of
      advanced prostate cancer.
AB  - The methods for treatment of advanced prostate cancer, based on the agonistic
      analogs of LH-RH were reviewed. New therapeutic approaches utilizing antagonistic
      analogs of LH-RH such as SB-75 (Cetrorelix) have been described. Analogs of LH-RH
      chemically linked to various cytotoxic radicals are also being developed.
      Combinations of LH-RH agonists or antagonists with superactive somatostatin
      analogues such as Octastatin (RC-160) or with bombesin/GRP antagonists are being
      investigated in order to delay or prevent the relapse and improve the therapy for
      prostate cancer.

PMID- 1363979
TI  - [Pancreatojejunostomy or pancreatogastrostomy after cephalic
      pancreatoduodenectomy].
AB  - The propensity for leakage at the site of pancreatojejunostomy continues to be a
      major reason for morbidity and death after pancreaticoduodenectomy.
      Pancreatogastrostomy has been introduced as a possible alternative to
      pancreatojejunostomy and although this procedure was developed experimentally
      more than 50 years ago its use has not gained widespread clinical use. The
      purpose of this study was to evaluate the role of pancreatogastrostomy.
      Pancreatogastrostomy was performed in 15 patients with pancreatic resection for
      carcinoma and compared with 57 pancreatojejunostomy. Our experience confirms that
      pancreatogastrostomy is a safe and easy method and suggest that it may be used
      more frequently.

PMID- 1363980
TI  - Efficacy of levocabastine in conjunctival provocation studies.
AB  - Levocabastine is a new topical histamine H1 antagonist. The antihistaminic and
      antiallergic effects of levocabastine eye drops have been evaluated in eight
      conjuctival provocation studies (n = 238). Two studies used a histamine
      challenge; five studies used allergen challenge; one study used both and in one
      study allergic provocation was with compound 48/80. In all but one study, only
      one single dose of levocabastine (one or two drops) was given. Six studies were
      against placebo only; one was against cromoglycate and one study used both
      placebo and cromoglycate as reference drugs. Single instillation of levocabastine
      eye drops protected against histamine and allergen-induced ocular symptoms within
      a period of 10 minutes. Levocabastine eye drops significantly alleviated
      conjunctival itching, redness, chemosis, eyelid swelling and tearing induced by
      histamine or allergen challenge (p < or = 0.05). Four hours after administration
      levocabastine was still active. With levocabastine, but not with cromoglycate, a
      significant increase was observed in the allergen threshold. Even when compared
      to cromoglycate given as a pre-treatment four times daily for two weeks before
      the allergen challenge, a single dose of levocabastine was significantly more
      effective in inhibiting hyperaemia, eyelid swelling, chemosis and tearing (all p
      < 0.05). In conclusion, conjunctival provocation studies have established that
      levocabastine has a rapid and long-lasting effect in protecting against histamine
      or allergen-induced conjunctival symptoms.

PMID- 1363981
TI  - New trends in the treatment of allergic conjunctivitis.
AB  - Histamine is the key mediator producing itching, redness and chemosis in allergic
      conjunctivitis. Histamine levels in tears are increased ten-fold in patients with
      this allergic condition. Levocabastine is a newly synthesized histamine H1
      antagonist which has been formulated as both eye drops and nasal spray. In well
      established assays of antihistamine activity, levocabastine was found to be the
      most potent antihistamine compound available, being 15,000 times more potent than
      chlorpheniramine. Ocular provocation studies in man have shown that levocabastine
      protects against the symptoms of allergen-induced conjunctivitis.
      Ophthalmological examinations, including slit lamp and ophthalmoscopy showed no
      adverse effects. Data from therapeutic studies are available for more than 1700
      patients with allergic conjunctivitis treated for 2-16 weeks. One drop of
      levocabastine (0.5 mg/ml) per eye given two to four times daily provided
      significantly better symptom control than placebo, with good to excellent results
      in 71% of patients on levocabastine compared to 55% on placebo (p < 0.001).
      Levocabastine has a fast onset of action. In one study 94% of patients
      experienced symptom relief within 15 minutes after the first instillation. The
      effects observed with levocabastine were at least as good as those with ocular
      cromoglycate or oral terfenadine. The incidence of adverse experiences was not
      different from placebo. Levocabastine promises to be a valuable treatment for
      patients with allergic conjunctivitis.

PMID- 1363982
TI  - Peripheral nerve segments promote consistent long-term survival of adrenal
      medulla transplants in the brain.
AB  - Patients with Parkinson's disease have received intracerebral transplants of
      autologous adrenal medulla in the attempt to counteract their severe motor
      dysfunctions. Unfortunately, in the majority of cases, clinical improvement has
      not persisted and there has been extremely poor survival of the grafts. Based on
      the recent observations of long-term viability of adrenal medulla grafts in the
      interior of transected peripheral nerves, adrenal medulla/peripheral nerve
      complexes were constructed in the brain to promote extended viability of
      chromaffin cells. A three-step, time-dependent transplantation procedure is
      described that results in a 100% survival rate of the adrenal medulla graft. The
      grafts consist of a stable population of approximately 2.0 x 10(3) chromaffin
      cells that survive for at least 6 months (longest time point studied):
      Immunoreactivity to catecholamine-related enzymes (tyrosine hydroxylase, dopamine
      beta-hydroxylase) and the low-affinity NGF receptor (192-IgG) are expressed by
      the chromaffin cells. The ultrastructural characteristics of the cells are normal
      and comparable to their in vivo counterparts. Construction of these peripheral
      nerve/adrenal medulla complexes evidently improves local conditions in and around
      the grafts, enabling the chromaffin cells to remain viable. This new methodology
      achieves the goal of reliable and extended survival of the adrenal medulla graft
      after intracerebral transplantation. The enhanced longevity now provides an
      opportunity to reevaluate the efficacy of the adrenal medulla transplant to
      ameliorate the functional disorders associated with striatal dopamine depletion,
      especially over long time periods.

PMID- 1363983
TI  - Autocrine and paracrine effects of peptides on human pituitary cells.
AB  - In contrast to normal human pituitaries, GH-secreting adenomas cannot process in
      vivo ProSRIH whereas they do it in vitro. The existence of an endogenous factor
      able to inhibit ProSRIH processing in vivo was postulated and such a role was
      analyzed for GHRH. Results showed that when GH adenomas are incubated in vitro
      with GHRH 10(-8) M, their ProSRIH contents are decreased, percent inhibition
      being negatively correlated to the amount of endogenously released GHRH. When
      incubation is performed in the presence of GHRH antibody in order to block the
      effect of endogenous GHRH, Pro-SRIH content is increased. The same effects are
      observed on SRIH release: inhibition by GHRH, stimulation by GHRH antibody.
      Normal rabbit serum had no effect. It may therefore be concluded that the absence
      of ProSRIH maturation observed in adenomas in vivo may be the consequence of the
      GHRH release that is known to be higher from GH adenomas than from normal
      pituitaries.

PMID- 1363984
TI  - Hormonal Resistance Syndromes. Proceedings of 35th International Henri-Pierre
      Klotz Symposium. Paris, May 14-15, 1992.

PMID- 1363985
TI  - [Inborn defects of neutrophils in peripheral blood I.Deficiency/lack of adhesion
      receptors (syndrome of leukocyte adhesion disturbance --syndrome LAD)].

PMID- 1363986
TI  - [Sulfasalazine in the treatment of rheumatoid arthritis. A multicenter open study
      of 150 patients during 6 months].
AB  - One hundred and fifty patients with rheumatoid arthritis were given sulfasalazine
      in a daily dosage of 2 g during an open-label, multicenter, six-month trial.
      Improvements were apparent as early as four weeks after initiation of the drug.
      Improvements in clinical parameters and erythrocyte sedimentation rate were
      statistically significant. In the patients who remained on the study protocol,
      clinical and biological improvements continued over time and were more marked
      after six months. Overall clinical safety was satisfactory: 30 patients were
      withdrawn from the trial for adverse events, all of which resolved after
      discontinuation of the study drug. Most of these adverse events (93%) developed
      within two months of initiation of the drug, demonstrating the need for
      hematologic and hepatic tests at regular intervals during the first three months
      of sulfasalazine therapy. Thirty-four patients had not previously received
      maintenance therapy; in this subgroup, only one patient was withdrawn for
      ineffectiveness. In view of its favorable risk/benefit ratio and fast action,
      sulfasalazine may be a useful first-line drug in patients with rheumatoid
      arthritis.

PMID- 1363988
TI  - The glycoprotein B gene and its syn3 locus of herpes simplex virus type 1 are
      involved in the synthesis of virus-associated growth factor (HSGF-1).
AB  - A putative growth factor (HSGF-1) associated with herpes simplex virus type 1
      (HSV-1), which is similar to PRGF associated with pseudorabies virus, and/or HSGF
      2 associated with HSV-2, was described. Experiments with four syncytial (syn) and
      four nonsyncytial (syn+) HSV-1 strains showed that the ability of this virus to
      produce HSGF-1 in infected cells is associated with the syn+ phenotype. Double
      infection of cells with syn+ and syn strain resulted either in enhancement or
      complete inhibition of HSGF-1 production, depending on the chosen pair of syn+
      and syn strains. The studies with the recombinants between the syn+ strain KOS
      and syn strain ANGpath in the gene for glycoprotein B (gB) and syn3 locus
      revealed that the gB gene and its syn3 locus play a role in the HSGF-1 synthesis.

PMID- 1363987
TI  - [Gold salt deposits in the conjunctiva in rheumatoid arthritis after gold
      therapy. A systematic study of 15 biopsies].
AB  - Ocular abnormalities have long been recognized as a potential adverse effect of
      gold therapy in patients with rheumatoid arthritis. Clinical symptoms and ocular
      tissue lesions possibly related to use of gold therapy were routinely evaluated
      in eleven patients. There were few clinical manifestations: only one patient had
      typical accumulation of gold in the anterior crystalloid. In contrast, routine
      ultrastructural and microprobe studies of conjunctival biopsy specimens disclosed
      accumulation of gold salts in every case. Gold was visible as aurosomes in the
      conjunctival macrophages. Aurosomes were seen in patients treated for as little
      as one month, occurred even with low doses (0.3 g), and were still visible after
      several years. Duration of accumulation can be roughly estimated on the basis of
      the morphologic appearance of aurosomes which are lamellar after a few weeks of
      gold therapy and rod-shaped beyond one month.

PMID- 1363989
TI  - Induction of MHC class I antigen expression following infection of a human
      esthesioneuroblastoma cell line with cytomegalovirus and human immunodeficiency
      virus.
AB  - Productive infections with cytomegalovirus (CMV) and human immunodeficiency virus
      (HIV) were established in the Tp41ON cell line derived from a human
      esthesioneuroblastoma. HIV antigen expression was highest in cultures coinfected
      with CMV and HIV. Viral infection caused increased MHC class I antigen expression
      while class II and CD4 antigens remained undetectable using immunofluorescence
      methods. Uninfected cultures showed 10% and coinfected cultures 80% class I
      antigen positive cells. In coinfected cultures, CMV and HIV antigens were
      detected in 4% and 8% of the cells, respectively. The detection of CMV antigens
      in some multinucleated cells suggests coinfection with both viruses in these
      cells, as multinucleated cells were not found in cultures infected with CMV only.
      The study shows that a cell line showing neuronal differentiation in vitro can be
      infected with CMV and HIV and that this infection increases MHC class I antigen
      expression.

PMID- 1363991
TI  - Expression of Helenium virus S coat protein in Escherichia coli, in vitro in
      rabbit reticulocyte lysate and transgenic tobacco.
AB  - The coat protein open reading frame (ORF) sequence of Helenium virus S (HelVS)
      was cloned and expressed in E. coli, rabbit reticulocyte and transgenic tobacco.
      In E. coli the size of the protein was identical to that obtained for the coat
      protein from purified virus particles and less than that predicted for the fusion
      protein. This may be due to ribosome binding at a potential ribosome binding site
      present on the viral sequence, approximately 45 nucleotides upstream from the
      initiating methionine of the coat protein ORF. This region of HelVS, equivalent
      to the 1.5 kb subgenomic RNA, also produced high levels of protein when
      transcribed and translated in vitro. When introduced into Nicotiana tabacum by
      leaf disk transformation via Agrobacterium tumefaciens, high levels of stable
      coat protein were detected which were identical in molecular weight to that of
      HelVS coat protein and constituted approximately 0.1-0.5% of the total extracted
      protein.

PMID- 1363992
TI  - ELISA and indirect immunofluorescence in the diagnosis of LCM virus infections.
AB  - Thirty-seven matched samples of patient sera with the clinical diagnosis of a
      lymphocytic choriomeningitis (LCM) infection, as well as 56 matched samples of
      patient sera with the clinical diagnosis of a CNS infection of vague etiology
      were examined. Two serological techniques, indirect immunofluorescence (IF) and
      ELISA were used. They revealed 16.2% of positive sera confirming the clinical
      diagnosis of the disease; in the cases of clinical diagnosis of CNS infection of
      vague etiology 8.9% of positive sera were found, which points to an LCM virus
      caused infection.

PMID- 1363990
TI  - Wild measles virus strain: isolation and identification.
AB  - Four isolates of measles virus (Gag, Il, Buk and Shed) were obtained from
      suspensions of mononuclear cells from patients at the active stage of the
      disease. Vero cells were used for the virus isolation. All the isolates caused in
      the infected cell culture the appearance of symplasts of differently sized, star-
      or spindle-shaped multinuclear cells. The specificity of cytopathic effect was
      proved by the adsorption of monkey erythrocytes on the surface of cells infected
      by virus. The isolates were identified in virus neutralization (VN) and
      haemagglutination inhibition (HI) tests with different immune preparations:
      measles-globulin (standard), hyperimmune sera to rubella and mumps viruses, Sch.
      Zonne and Sch. Flexneria, as well as with conjugates of sera from measles
      patients and those vaccinated with live measles vaccine (LMV) L-16.

PMID- 1363994
TI  - Immunoelectron microscopy of rabbit haemorrhagic disease virus using monoclonal
      antibodies.
AB  - Five monoclonal antibodies (MoAbs) to rabbit haemorrhagic disease virus (RHDV),
      prepared and tested in ELISA, immunoperoxidase (IP) and immunofluorescence (IF)
      test previously, reacted specifically in immunoelectron microscopy (IEM), too. No
      differences in binding of individual MoAbs with full or empty RHDV particles were
      found by IEM.

PMID- 1363993
TI  - SSPE in Slovakia: immunocytochemical study.
AB  - In a retrospective study of two patients from Slovakia with clinical, virological
      and histopathological diagnosis of subacute sclerosing panencephalitis (SSPE),
      measles virus antigen was detected by immunocytochemical labelling studies. The
      formalin fixed, paraffin-embedded thin brain sections labelled with anti-measles
      antibodies and avidin-biotin complex peroxidase were counterstained with
      haematoxylin. Only a single area of brain was examined in each patient:
      cerebellum and parietal lobe. Viral antigen positive reaction was identified
      within Purkinje cells and extending along dendritic processes in cerebellum, and
      also in oligodendrocytes of subparietal white matter.

PMID- 1363996
TI  - [The role of the brain dopaminergic mechanisms in different models of anxiety
      states].

PMID- 1363995
TI  - [Heart valvular and coronary manifestations of Takayasu disease. Apropos of a
      surgically-treated case].
AB  - Cardiac involvement in Takayasu's disease is well documented. This is often the
      result of severe hypertension. However, severe clinical manifestations of aortic
      regurgitation and coronary insufficiency are much less common. The authors report
      a case in which post-infarction angina and severe left ventricular failure led to
      a double valve replacement and an aorto-right coronary bypass graft procedure.
      The diagnosis of Takayasu's disease was suspected before surgery and was
      confirmed by histological examination.

PMID- 1363997
TI  - [The study of rapid calculation on clearance creatinine rate in normal and
      epidemic hemorrhagic fever].
AB  - Height, weigh, urine volume/24 hours, serum creatinine (Scr) and urine creatinine
      were measured in 207 normal people and 232 patients with EHF. The clearance
      Creatinine rate (Ccr) was calculated by 24 hour urine volume method (therapy
      measure method) and Cockcroft's method (formulation method). The clearance
      creatinine rates between the two methods compared were significantly positive
      correlation, but the average values of Ccr in different stages in EHF were
      significantly different (P < 0.01). The result indicated that Cockcroft's
      Formulation was not fit for HFRS. According to the difference of Ccr in each
      stages of EHF, the adjustment values (ad) were presented and used to correct
      Cockcroft's formulation, thus, the adjusted Cockcroft's formulation could be
      obtained: Ccr = (140-ad-Age) x W/72 x Scr. In this paper, the Ccr of the adjusted
      method was compared with that of therapy measure method, the average values
      calculated by two methods were not different (P > 0.05). The result of 14 EHF
      Clinic practice demonstrated that between adjustment and practice measured
      methods were not significantly different. It shows that adjustment method is
      practical and available and can be used easily by clinic doctors in basic
      hospital.

PMID- 1363998
TI  - [Familial pheocromocytoma. Report of 4 families].
AB  - Twelve patients with pheochromocytomas were found in members of 4 families in the
      recent 25 years. Nine of them were treated and confirmed surgically. Follow-up
      showed that 50% of the members were found to suffer from pheochromocytomas. Six
      of the 9 patients had bilateral and multiple tumors. The tumors developed in the
      adrenal glands and benign in nature. Three of the 12 patients were associated
      with thyroid tumors. Peripheral leukocyte chromosomes were studied in two
      families. Chromosomal analysis showed no evidence of marker on the 15th
      chromosomal pair. These findings were not consistent with the previous results.
      Tumor tissue contents of catecholamine were determined in 4 familial tumors and
      14 sporadic pheochromocytomas. Familial pheochromocytomas tissue contained
      significantly higher norepinephrine and epinephrine than the sporadic tumors.

PMID- 1364000
TI  - Clinical Application of Cytokines in Pediatric Oncology. Proceedings of a
      symposium at the XXIII Meeting of the International Society of Pediatric
      Oncology. Rhodes, Greece, October 1-4, 1991.

PMID- 1363999
TI  - Proceedings of the 39th Symposium on Toxins. Awaji Island, July 15-17, 1992.

PMID- 1364001
TI  - Effects of sexual condition and age on carcass characteristics and grading of
      Sussex cattle in Zimbabwe.
AB  - The effects of sexual condition and age at slaughter on carcass characteristics
      were investigated in Sussex cattle. At three months of age 93 male calves were
      allocated to three sexual treatments: entire, cryptorchid and castrate. The
      cattle were weaned at eight months, grazed on range and then placed into feedlots
      for 90 days prior to slaughter at 15, 18 or 21 months of age. Entire and
      cryptorchid cattle gained more (P < 0.01) weight and had heavier and learner
      carcasses than the castrates. Although cattle slaughtered at 15 months of age had
      better fleshing grades than those slaughtered at 18 or 21 months of age, no
      animal was down-graded for exhibiting marked secondary sexual characteristics.

PMID- 1364003
TI  - IVth International Symposium on Neural Transplantation. Washington, D.C. July 12
      16, 1992. Abstracts.

PMID- 1364002
TI  - Takayasu's arteritis with aortoaortic bypass graft and renal autotransplantation:
      report of one case.
AB  - Takayasu's arteritis is a rare inflammatory disease of the aorta and its major
      branches which occurs predominantly in young women. The clinical course has been
      described as two stages: 1) initial phase, with inflammatory process and systemic
      manifestations; and later 2) pulseless phase, with multiple arterial occlusions.
      A 20-year-old female came to visit this hospital for the first time at 10 years
      of age with occlusion of the left subclavian artery and of the thoracoabdominal
      aorta. Aortoaortic bypass surgery was performed using a 14 mm woven graft from
      the ascending aorta to the descending aorta on the infrarenal portion. The
      postoperative course was uneventful. Exertional dyspnea and hypertension
      progressively developed. However, in the past year, angiograms have shown a
      marked stenosis on the proximal portion of the left renal artery.
      Autotransplantation for the left-sided kidney was performed. The patient did
      well, and remained free of symptoms until this time of writing, 12 months after
      the operation.

PMID- 1364007
TI  - Age-related changes in immune reactivity: the influence of intrinsic defects and
      of a changed composition of the CD4+ T cell compartment.
AB  - Aging is accompanied by a decline in immune reactivity which to a major extent
      can be attributed to changes at the level of regulatory CD4+ T cells. In addition
      to evidence pointing to intrinsic defects, resulting in improper responsiveness
      of lymphocytes, it is likely that many age-related phenomena can be explained by
      a changed composition of the T cell compartment. Most likely as a consequence of
      thymic involution, the fraction of naive T cells in the periphery decreases,
      resulting in poor responses to neoantigens in particular. Moreover, due to
      antigenic exposure the fraction of memory cells increases. It is likely that,
      regardless of their phenotype, cells from aged individuals are subject to
      intrinsic defects or to immunosuppression, resulting in a lower responsiveness.
      As far as CD4+ T cells are concerned, recent studies have demonstrated that naive
      and memory cells behave differently with regard to activation requirements and
      lymphokine production. Age-related changes in T cell reactivity will be discussed
      in the context of these observations.

PMID- 1364005
TI  - [The late results of using evicrol and stomadent for eliminating dental tissue
      defects in children].
AB  - Clinical analysis of the efficacies of evikrol and stomadent used to replace
      dental hard tissue defects in children has shown similar results, but stomadent
      is preferable because the filling made of it virtually does not change its color.
      The authors claim that the development of such complications as caries
      recurrence, change of the color of the filling in sites of their union with
      dental tissues, abnormal edge union is related to the technique of enamel acid
      tanning of immature children's teeth, that should be modified.

PMID- 1364004
TI  - [Clinical sequelae of genetically determined polymorphisms of drug oxidation].

PMID- 1364006
TI  - [Drug treatments of atrial fibrillation].
AB  - Atrial fibrillation is a daily cardiological problem which poses three types of
      questions, which, though old, are only partially mastered: anticoagulation,
      reduction and prevention of recurrence. It is a potent source of embolism. The
      risk is the greatest in patients with rheumatic valvular disease when the
      fibrillation is recent and when underlying cardiac disease is uncompensated. Long
      term anticoagulation is mandatory when the cause is rheumatic heart disease. In
      other pathologies, though anticoagulation has not been shown to reduce mortality,
      it significantly reduces the number of cerebrovascular accidents, including in
      the elderly and with low-dose vitamin K antagonist drugs. The efficacy of
      anticoagulation in preventing arterial embolism has not been established.
      Reduction of atrial fibrillation is not essential if the arrhythmia is well
      tolerated, chronic, especially in elderly patients and when several recurrences
      have occurred despite preventive therapy. In other cases, medical reduction is to
      be preferred to cardioversion if the fibrillation is recent and well tolerated.
      Of the oral and injectable preparations, amiodarone seems to be the drug with
      best benefit/risk ratio. Prevention of recurrence of fibrillation is unnecessary
      for many after a first episode, especially when idiopathic. In other cases, there
      are many available drugs but results are uncertain except in those observed in
      atrial fibrillation related to the autonomic nervous system. Strictly controlled
      and statistically exploitable studies show comparable efficacy of quinine and
      other Class I drugs. Beta-blockers are not very useful and the excellent long
      term results with amiodarone require confirmation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1364008
TI  - Hidden amyloidoses.
AB  - The pathogenesis as well as the genetic disposition to develop clinical symptoms
      in transmissible spongiform encephalopathies (e.g. Creutzfeldt-Jakob disease,
      scrapie, bovine spongiform encephalopathy) relate these diseases to classical
      noninfectious amyloidoses (familial amyloidotic polyneuropathy as an example) and
      to Alzheimer's disease. This is not obvious to the nonexpert at first glance.
      This communication tries to elucidate this association, to reveal which
      immunochemical techniques have contributed their share.

PMID- 1364009
TI  - An SphI polymorphism at the vinculin locus (VCL).

PMID- 1364010
TI  - TaqI polymorphisms at the annexin VIII locus (ANX8).

PMID- 1364011
TI  - An SphI polymorphism at the ZNF22 locus.

PMID- 1364012
TI  - A new VNTR-type RFLP probe (lambda TM-18) on chromosome 1 (D1S157).

PMID- 1364013
TI  - A new VNTR-type RFLP probe (ChdTC-114) on chromosome 20p (D20S72).

PMID- 1364014
TI  - [Prevention of pancreatic fistula in pancreaticoduodenectomy: cannulation of the
      pancreatic duct].
AB  - Fifty-two patients with malignant tumours underwent pancreaticoduodenectomy in
      the past 13 years. A plastic catheter, 3 mm in diameter and 40 cm in length, was
      used for pancreatic duct drainage and stent, with one end of it inserted into the
      pancreatic duct and the other end in the jejunal lumen. The cannulation was found
      to be very effective in stenting the stump pancreatic duct and draining the
      pancreatic juice away from the anastomotic stoma, hence preventing postoperative
      leakage. Temporary postoperative fistula occurred in only one patient, and
      operative death was noted.

PMID- 1364016
TI  - [Culicidae (Diptera: Culicidae) of the Perus river basin, Acre, Amazonia
      (Brazil)].
AB  - Mosquito (Diptera: Culicidae) collections were made on the Pedro Peixoto
      Colonization Project in the State of Acre, Brazil. Four thousand, five hundred
      and eighty-eight (4,588) specimens were collected and fifty-three (53) species or
      group recognised. The occurrence of Anopheles (Nyssorhynchus) oswaldoi is given
      special emphasis.

PMID- 1364017
TI  - Evidence for an altered kinetics of DNA excision-repair in cells infected by
      herpes simplex virus type 1.
AB  - In cells infected with herpesviruses a series of host cell nuclear changes can be
      observed in a temporal sequence. Such changes include chromosome aberrations. The
      precise mechanism by which virus infection produces chromosome damage is not
      known, but we have previously reported that herpes simplex virus type 1 (HSV-1)
      induces a significant number of single-stranded breaks in the host cell DNA at
      early hours of infection and in a time-dependent fashion. Here, it is reported
      that HSV-1-infected cells subjected to irradiation with ultraviolet light, show
      an altered kinetics in the normal process of DNA excision-repair at early hours
      of infection.

PMID- 1364015
TI  - Effects of urogastrone-epidermal growth factor and age at administration on five
      enzymes in the small intestine of suckling rats.
AB  - Suckling rats were given urogastrone-epidermal growth factor (EGF: 1,000
      micrograms/kg body weight) or vehicle by gavage at one of three stages of
      development: 8 to 10, 11 to 13 or 14 to 16 days of age. Intubation was carried
      out at 8-hourly intervals over these periods. Fourteen to 16 h after the last
      intubation the rats were killed; that is, at 11, 14 and 17 days respectively.
      Samples of proximal and distal small intestine (SI) were taken for enzyme
      analysis. Five enzymes were assayed; sucrase, lactase, gamma-glutamyl
      transferase, alkaline phosphatase and neutral amino-peptidase, and their
      activities expressed per g protein. Treatment with EGF had no effect on body
      weight or on the length of the small intestine at any age. The nature of the
      effects on enzyme activities depended on the specific enzyme concerned, the site
      within the small intestine and the timing of the treatment. Lactase was increased
      by EGF at both sites only on day 14, whereas gamma-glutamyl transferase was
      increased in proximal samples at 11 and 14 days, and in distal samples at 17
      days. Nor was the outcome always to increase activity. On day 11 alkaline
      phosphatase was increased in proximal SI, but decreased in distal SI; and so too
      was aminopeptidase N decreased in distal SI at 11 days. Sucrase showed no
      response at all. The pattern is complex. Certainly it does not indicate
      accelerated functional maturation.

PMID- 1364018
TI  - HPLC-monitoring of AZT in HIV-infected patient's plasma: a critical study.
AB  - 3'-azido-2', 3'-deoxythymidine (AZT) concentrations in spiked human plasma were
      determined by means of reversed-phase high performance liquid chromatography (RP
      HPLC). Samples were first cleaned-up for analysis using solid-phase extraction
      (SPE) columns filled with Silipore C18. In the concentration range comprising
      usual peak plasma concentrations during AZT therapy (0.1-20 mumol/l, i.e. 0.026
      5.34 micrograms/ml) mean efficiency of the extraction procedure reached as high
      as 75.3% of original AZT concentrations in standard unextracted aqueous
      solutions. Replicate analyses in this range gave satisfactory intra-assay
      precision and reproducibility with coefficient of variation less than 11.3%.
      Calibration curves both in water and plasma showed good linearity (r > 0.999).
      The detection limit in plasma was 2 mumol/l, i.e. 5.3 ng per a 20 microliter of
      sample injected to the HPLC column. Plasma levels of AZT after a single dose
      administration, determined by HPLC and RIA showed rather poor correlation (r =
      0.8900). In RIA about 1.7-4.5 times higher concentration values were obtained in
      a relatively short time, and, consequently, this method may better fulfil the
      needs of routine drug monitoring.

PMID- 1364019
TI  - Factors influencing immune electron microscopy of flexuous potato viruses.
AB  - Effects of pH of extraction buffers, pH and titer of trapping antisera and their
      combinations, virus acquisition time and virus host on the trapping efficiency of
      flexuous potato viruses X, S and Y (PVX, PVS and PVY) in immune electron
      microscopy were evaluated. Addition of ethylene-diamine-tetraacetic acid to the
      extraction buffer improved trapping of PVY, adversely affected PVS but not PVX.
      Combinations of antisera had differential adverse effect on trapping which was
      maximum with the mixture of three antisera. Mixture of antisera to PVX and PVY
      had the least adverse effect on trapping of PVX and PVY as compared to the
      mixture with PVS antiserum. Trapping of PVX and PVY was good and almost at par at
      all the dilutions of the antisera while that of PVS was good up to 1000-fold
      only. Prolonged virus acquisition time significantly increased the number of
      virions trapped. Trapping was affected both by the pH of the antiserum and the
      extraction buffer, while in the case of PVY it was also affected by the host
      species.

PMID- 1364020
TI  - Effect of enterovirus infection on susceptibility of HeLa cells to Shigella
      flexneri invasivity.
AB  - Invasiveness of Shigella flexneri M90T in HeLa cells was significantly increased
      when cells were preinfected with poliovirus 1, coxsackievirus B3 and echovirus 6.
      This effect was dependent on the dose of virus used, evident at early stages of
      viral infection and lasted hours before the appearance of a cytopathic effect. An
      increase of bacterial invasion ability was also noticed when HeLa cells were
      incubated with UV-inactivated enteroviruses. This enhancing effect obtained with
      both viable and UV-inactivated enteroviruses was not observed when in coinfection
      experiments HN555, a mutant of S. flexneri M90T which lacked invasive properties,
      was used. The data presented here suggest that the early steps of enterovirus
      infection induce some alterations of HeLa cells which are responsible for the
      enhancing of the invasiveness of S. flexneri M90T, but not sufficient to promote
      internalization of a non-invasive strain.

PMID- 1364021
TI  - Significance of long lasting persistence of influenza virus antigens at the
      portal of infection and in the spleen of mice.
AB  - Distribution of virus, its antigens and development of cellular factors of
      immunity were followed in the course of different forms of acute influenza virus
      infection in mice. Long term persistence of influenza virus antigens in the
      portal of entry and spleen were typical for of acute influenza. Lethal effect of
      influenza infection was caused by massive lesions induced by the virus and due to
      cell mediated immune response. The fate of infected individual seems to be
      decided during the first days of post-inoculation and depends on the ability of
      the virus to modify the cell membranes of the infected individual.

PMID- 1364022
TI  - Study of cross-reaction between Coxiella burnetii and Legionella pneumophila
      using indirect immunofluorescence assay and immunoblotting.
AB  - Patients with Q fever and legionellosis may present identical clinical symptom.
      Differentiation of these diseases is made by serology, mainly the indirect
      immunofluorescence assay (IFA). Using IFA the authors tested 154 Q fever positive
      sera from 55 patients with acute Q fever and 28 patients with chronic Q fever for
      Legionella pneumophila antibodies and 57 sera from 57 patients with legionellosis
      for Coxiella burnetii antibodies. Of the 211 sera tested, four sera from
      different patients had antibodies to both C. burnetii and L. pneumophila. Using
      cross-adsorption studies and protein immunoblotting, no cross-reaction between C.
      burnetii and L. pneumophila antibodies could be identified. The moderate antibody
      titers against L. pneumophila in two Q fever patients and vice versa for one
      legionellosis patient are consistent with the incidence of seroprevalence in
      healthy blood donors and were not due to cross-reactivity. One patient was
      identified with concurrent Q fever and legionellosis.

PMID- 1364023
TI  - Peroral immunization of adult white mice with the Skalica strain from the tick
      borne encephalitis virus complex.
AB  - Adult white mice immunized perorally with the infectious Skalica strain from the
      tick-borne encephalitis (TBE) virus complex did not show any clinical symptoms of
      illness. 56% of experimental animals immunized with two doses of the Skalica
      virus (the titer of virus was 6 x 10(10) LD50) were protected against the
      challenge with the Hypr strain of TBE virus. All mice immunized with the Skalica
      virus and having haemagglutination-inhibiting antibodies higher than 1:80
      survived the challenge with the given dose of virulent TBE virus. No differences
      in the immunogenicity and protectivity were observed in experimental animals
      infected with infectious Skalica virus by oesophageal probe, or by drinking virus
      containing medium. A higher protective activity against the virulent Hypr virus
      was observed in adult white mice immunized subcutaneously with the Skalica virus.

PMID- 1364025
TI  - The effect of an Egyptian isolate of Streptomyces afghanensis on some plant
      viruses.
AB  - An Egyptian isolate of Streptomyces afghanensis was examined for the production
      of antiviral metabolites. Concentrated broth exudates of this microorganism were
      tested against tobacco mosaic virus (TMV), tomato mosaic virus (ToMV) and potato
      virus X (PVX) infecting Nicotiana tabacum L. cv. White Burley. Both concentrated
      metabolites and their acetone extract inhibited local lesion development of the
      tested viruses. In all cases, maximum antiviral effect was observed 2 hr after
      infection. The ultrafiltrate of broth culture reduced the number of local PVX
      lesions produced on the challenged half leaves in the case of later applications.

PMID- 1364024
TI  - A study on the immune response of sheep to foot and mouth disease virus vaccine
      type 'O' prepared with different inactivants and adjuvants.
AB  - Foot and mouth disease virus (FMDV) type 'O' was inactivated either with
      formaldehyde or binaryethyleneimine (BEI). Vaccines were prepared with
      inactivated virus incorporating aluminum hydroxide gel or mineral oil as an
      adjuvant. The antibody response in sheep was monitored by serum neutralization
      and ELISA test for a period of six months. Significant difference in antibody
      response was not observed between vaccines inactivated with formaldehyde or BEI.
      On the other hand significant difference in the antibody response was noticed
      between alhydrogel and oil vaccines. The high titer of antibodies stimulated by
      oil adjuvant vaccines persisted longer than those of alhydrogel vaccines within
      the period of study.

PMID- 1364026
TI  - A method for the preparation of purified antigens of coxsackievirus B3 from a
      large volume of cell culture supernatant.
AB  - A simple procedure was used for the concentration and partial purification of
      coxsackievirus B3 (Nancy strain). For a large-scale production of virus. Vero
      cells grown in roller bottles were used. Virus concentrate from a large volume of
      cell culture supernatant was prepared by precipitation with 6% (w/w) polyethylene
      glycol. This crude antigen was further purified by banding in cesium chloride
      gradient using ultracentrifugation. The infectivity and haemagglutination
      activity of virus were checked up during the whole procedure and the final
      recovery of infections virus was about 60%.

PMID- 1364027
TI  - The use of consensus sequence for amplification and oriented cloning of human
      alpha interferon genes.
AB  - A clone from human cDNA library was amplified in polymerase chain reaction (PCR)
      by the synthetic oligonucleotides. The final construct after linker ligation and
      digestion with restriction endonucleases was suitable for oriented cloning into
      E. coli expression vector. The interferon (IFN) expression could be detected by
      SDS-PAGE electrophoresis. Western blotting and biological antiviral assay. This
      set of oligonucleotides can be used also for amplification of genomic DNA or cDNA
      libraries.

PMID- 1364028
TI  - Expression of HIV-2 Gag and Env antigens in E. coli.

PMID- 1364029
TI  - Attempt to infect Hunterellus hookeri Howard (Hymenoptera, Encyrtidae), an
      endoparasite of ticks, with Coxiella burnetti.

PMID- 1364030
TI  - Hantavirus isolation from birds.

PMID- 1364031
TI  - [Mixed anginas: therapeutic implications].

PMID- 1364032
TI  - Protective effects of berberine and phentolamine on myocardial reoxygenation
      damage.
AB  - The protective effects of berberine and phentolamine against anoxia and
      reoxygenation damage in isolated rat hearts have been investigated. Incorporation
      of berberine (24.5 mumol/L) in both anoxic and aerobic perfusion media resulted
      in a significant reduction of CPK release during the reoxygenation period, and
      the ultrastructural damage was reduced as compared with the control group; the
      myocytes in the berberine-treated group displayed mild intracellular edema, well
      registered myofibrils without contracted bands, and swollen mitochondria with
      partially broken cristae but without dense bodies. Berberine did not inhibit
      calcium and sodium accumulation or magnesium and potassium loss. Treatment with
      phentolamine (6.6 mumol/L), an alpha-adrenoceptor antagonist, had similar
      effects, though the CPK release profile was shifted to the right and downwards.
      These results suggest that although berberine and phentolamine have some
      beneficial effects on myocardial reoxygenation injury, they may not abolish the
      injury. Therefore alpha-adrenoceptor stimulation may not be the major mechanism
      behind the injury.

PMID- 1364033
TI  - Microtubules and regulation of granulosa cell steroidogenesis by porcine
      granulosa cell conditioned medium.
AB  - Possible involvement of microtubules in the regulation of granulosa cell
      steroidogenesis by large follicle granulosa cell conditioned media (LGCCM) was
      assessed by monitoring the effect of agents that alter the cytoplasmic
      microtubule-tubulin equilibrium. The changes in microtubule organization and cell
      shape were examined by immunohistochemical procedure and morphometric analysis.
      Progesterone production stimulated by LGCCM was reduced by colchicine (agent that
      polymerizes microtubules) in a dose-dependent manner. In contrast, LGCCM
      stimulated progesterone secretion was significantly decreased by microtubule
      stabilizing agent (taxol: 1-10 microM). Cultured granulosa cells with a flattened
      appearance and projections after 24 h of incubation assumed a spherical
      configuration and were devoid of cytoplasmic processes when cultured with these
      agents. LGCCM stimulated GCs showed a reduction in the perimeter as compared with
      controls, although some cytoplasmic processes were observed. These findings
      suggest the involvement of microtubules in the regulation of cultured granulosa
      cell progesterone production by LGCCM, possibly through an effect on subcellular
      organelle distribution by altering the morphology of granulosa cells.

PMID- 1364034
TI  - Peptide YY inhibits gastric acid secretion stimulated by the autonomic nervous
      system.
AB  - Peptide YY (PYY), a new peptide found primarily in mucosal endocrine cells of the
      terminal ileum and colon, inhibits pentagastrin-stimulated gastric acid secretion
      in several species, including man. Several studies indicate that PYY can affect
      autonomic neurotransmission, and we have recently shown that PYY can inhibit
      neurally stimulated release of insulin. The purpose of the present study was to
      examine the effect of PYY on gastric acid secretion stimulated by the autonomic
      nervous system. On separate days, 6 dogs that were prepared with chronic gastric
      cannulas were given 2-deoxy-D-glucose (2-DG; 90 mg/kg, i.v.) for 6 min, either
      alone, or in combination with PYY (100, 200, or 400 pmol.kg-1.h-1, i.v.) for 60
      min. The effect of PYY, at 400 pmol.kg-1.h-1, on gastric acid secretion
      stimulated by either 2-DG or PG (1 micrograms.kg-1.h-1, i.v.) was studied after
      treatment with propranolol (0.5 mg/kg, i.v. bolus) or phentolamine 1 mg/kg, i.v.
      bolus). PYY reduced the 2-DG-stimulated secretion of gastric acid in a dose
      dependent manner. PYY, given at 100 pmol.kg-1.h-1, reduced gastric acid output by
      29 +/- 17%; PYY, at 200, by 41 +/- 7% (p < 0.05), and PYY, at 400, by 52 +/- 8%
      (p < 0.05). The inhibitory action of PYY on 2-DG-stimulated secretion of gastric
      acid persisted after treatment with phentolamine (69 +/- 14%; p < 0.05), but it
      was blocked by treatment with propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364035
TI  - Tyrosine-hydroxylase-immunoreactive neurons in retinal transplants in the rat.
AB  - Embryonic rat retinae were transplanted to the brains of newborn rats, and the
      distribution of catecholaminergic neurons in the retinal tissue was studied 1-2
      months after transplantation, using the tyrosine hydroxylase (TH)
      immunohistochemical method. The results showed that distinct TH-positive cells
      were identified in all retinal transplants examined. The somata of the majority
      of these TH-immunoreactive cells were located along the inner margin of the inner
      nuclear layer in the retinal transplants; the processes of these cells were
      distributed mainly in the outer portion of the inner plexiform layer. This
      pattern is comparable to that observed in retinae of normal and host rats,
      suggesting that the organization of the catecholaminergic neurons in the
      transplant is largely similar to that in the normal retina. However, a reduction
      of the immunoreactivity in the plexiform layers and subpopulations of TH-positive
      cells with somatic diameter smaller than 8 microns or larger than 18 microns was
      observed in most of the retinal transplants studied. This implies that the
      organization of the catecholaminergic system in the transplant may not be as
      intact as in the normal retina.

PMID- 1364036
TI  - [Side effects of drugs most frequently used in and acute respiratory infections
      and diarrhea].

PMID- 1364037
TI  - Abstracts from the 10th Annual Symposium on Nonhuman Primate Models for AIDS. San
      Juan, Puerto Rico, November 17-19, 1992.

PMID- 1364038
TI  - Pheochromocytoma in the pregnant patient: a case study.
AB  - This is a case study of a patient 32 weeks pregnant who presented with multiple
      endocrine neoplasia type IIa, with severe pheochromocytoma complicated by adult
      respiratory distress syndrome. The patient's blood pressure was labile, with
      systolic variations from 50 to 230 mm Hg and tachycardia ranging from 150 to 180
      beats per minute. The patient was treated with a variety of alpha- and beta
      blockers whose efficacy is compared. Hemodynamic measures are compared with the
      clinical presentation. The importance of fluid replacement is discussed.

PMID- 1364040
TI  - Somatostatin inhibits VIP- and forskolin-stimulated cyclic AMP accumulation in
      enterocytes from rat jejunum.
AB  - This study demonstrates the dual regulation by somatostatin of vasoactive
      intestinal peptide (VIP)-stimulated and forskolin-stimulated cyclic AMP
      accumulation by isolated rat intestinal epithelial cells. Somatostatin non
      competitively inhibited (IC50 = 1 microM) the stimulatory effect of VIP on cyclic
      AMP accumulation, suggesting that the two neuropeptides act through separate
      receptors. The cyclic AMP accumulation produced by forskolin (a diterpene that
      stimulates directly the catalytic subunit of adenylate cyclase) was also
      inhibited by somatostatin in a dose-dependent manner. However, somatostatin did
      not modify the stimulatory effect of VIP on adenylate cyclase activity in a
      membrane preparation from the same cells, making it difficult to explain the
      mechanism of somatostatin action at this level. The data presented here suggest
      that somatostatin may play a physiological role in the regulation of nutrient
      absorption and the release of gut hormones or exocrine secretions by intestinal
      epithelial cells through the modulation of cyclic AMP production.

PMID- 1364039
TI  - Functional modifications of the coupling of solubilized dopamine D2 receptors to
      guanine-nucleotide-binding proteins.
AB  - The molecular basis for the regulation of high-affinity agonist, [3H]N-n
      propylnorapomorphine ([3H]NPA), binding to cholate-solubilized dopamine D2
      receptors was characterized using cations, guanine nucleotides and sulfhydryl
      modifying agents. [3H]NPA binding displayed an absolute requirement for divalent
      cations in the solubilized preparation. Removal of Na+ from the solubilized
      preparation caused an apparent reconstitution of soluble receptors resulting in a
      reduced sensitivity of the agonist binding to divalent cations. The
      pharmacological profile of [3H]NPA binding was found to be similar in membrane
      and solubilized preparations. N-ethylmaleimide (NEM) and thermal exposure
      mimicked the effects of guanine nucleotides in reducing the proportion of high
      affinity agonist sites in the solubilized state. [3H]NPA binding was much more
      susceptible to NEM-induced alkylation or heat inactivation compared to the
      antagonist [3H]spiroperidol binding. Pertussis-toxin-catalyzed ADP-ribosylation
      of G-proteins in the solubilized preparation resulted in the labelling of only
      one protein with the apparent molecular weight of 39-41 kDa. Both NEM and heat
      treatments caused the loss of ADP-ribosylation in the solubilized preparations. A
      consistent pattern of correlation between receptor binding data and ADP
      ribosylation response suggests functional coupling of dopamine D2 receptors to
      the components of the effector system in solution.

PMID- 1364041
TI  - Keratinocyte transglutaminase: differentiation marker and member of an extended
      family.
AB  - Transglutaminases stabilize a variety of biological structures by cross-linking
      constituent proteins. This action appears physiologically important in
      stabilizing (1) keratinocyte cornified envelopes, (2) fibrin clots, (3) the
      copulation plug in rodents, and (4) the fertilized egg surface in aquatic
      species. Several transglutaminases that participate in such processes have been
      well characterized and found, though highly divergent, to differ in sequence
      primarily at the amino terminus. Comparison of their gene structures suggests a
      likely mechanism by which new members may arise that assume a diversity of
      functions. The functions of some members of this family are presently unknown,
      including the tissue transglutaminase found in many mammalian cell types, and
      those found in plants. Most of the transglutaminases identified are soluble
      enzymes, but several that are membrane-bound have gained recognition recently.
      The best characterized of the latter is keratinocyte transglutaminase, which is
      anchored in the membrane by acylated fatty acid. Important for proper epidermal
      cell maturation, expression of this enzyme is greatly altered by physiological
      effectors and toxic agents. In addition, it is induced by cultivation of cells
      from non-squamous epithelia. Thus, it is a promising marker for helping to
      elucidate the molecular basis by which keratinocyte differentiation is elicited
      or altered.

PMID- 1364043
TI  - Genome type analysis of adenovirus type 4.
AB  - Twenty AV4 isolates were analysed with 18 restriction endonucleases. They could
      be classified into two genome types (genomic clusters) AV4p and AV4a. Combined
      with data from Li and Wadell [Arch Virol 1988;101:65-77], DNA variants p1-p8 and
      al-a3 were defined. The genetic relatedness within the genome types was in the
      range of 88-99% comigrating fragments, whereas < 62% of the fragments were
      comigrating between the genome types.

PMID- 1364042
TI  - [Experimental models of epilepsy].

PMID- 1364044
TI  - [15th Brazilian Congress of Neurology. Porto Alegre, 10-15 October 1992.
      Abstracts].

PMID- 1364045
TI  - Multidrug resistance in leukaemia.
AB  - Multidrug resistance hampers successful chemotherapy in many haematological
      neoplasms and is mediated by several cellular proteins. In some cases, the genes
      encoding these proteins have been shown to confer resistance on transfer to drug
      sensitive cell lines. This is true for the efflux pump product of the MDR1 gene,
      P-170. Upregulation of enzymes such as GST has been observed, although the
      contribution of this enzyme in drug resistance expressed by malignant
      haematopoietic cells is still uncertain. Cells also appear to be able to
      downregulate enzymes which are drug targets. Examples include the decrease in
      Topo II which accompanies the resistance shown by cells to VP-16 and VM-26.
      Although many reports include both presentation and relapsed patients, there are
      few data on samples drawn from the same patients before and after chemotherapy.
      While P-170 and GST appear to be raised more often in cells from resistant and
      relapsed disease, it is quite clear that such mechanisms can be active in de novo
      malignancy and do not necessarily emerge as a consequence of prior chemotherapy.
      Methods of detecting drug resistance are reviewed here; these include in vitro
      cellular assays for drug toxicity, and molecular, immunological and functional
      detection of P-170 or Topo II. The clinical evaluation of such assays is only
      just beginning and some of the data are contradictory. To some extent, this may
      reflect the complex way in which the various resistance mechanisms may interact.
      Nevertheless, there are some encouraging early signs that the application of
      these assays to clinical material will yield valuable data on the relative
      contributions of these mechanisms and on ways in which they may be overcome. At
      present, much attention has focused on the potential of agents which prevent the
      P-170 efflux pump from exporting cytotoxics from the cell. This is likely to be
      only the first of new therapies arising from an improved understanding of
      multidrug resistance. More immediately, assays for multidrug resistance and its
      parameters may find their place as routine diagnostic and prognostic tools in the
      laboratory.

PMID- 1364046
TI  - Factors governing the potentiation of NMDA receptor-mediated responses in
      hippocampus.
AB  - A modified medium containing an AMPA receptor antagonist and low concentrations
      of magnesium was used to investigate the factors governing the potentiation of
      synaptic responses mediated by NMDA receptors. When long-term potentiation (LTP)
      was induced in standard medium and NMDA responses were analyzed by changing to
      the modified medium, no statistically significant differences were observed
      between potentiated and control pathways. Returning the slices to the standard
      medium showed that LTP was still present, indicating that the potentiation effect
      was not reversed by the modified medium. High-frequency stimulation applied in
      the modified medium produced an enhancement of synaptic responses, but this was
      not occluded by prior potentiation in standard medium. The degree of potentiation
      induced in the modified medium and expressed by NMDA responses was larger in the
      presence than in the absence of inhibition and, unlike LTP, was proportionately
      larger when recorded in the stratum pyramidale than in the stratum radiatum.
      These results indicate that the potentiation of NMDA receptor-mediated responses
      triggered by high-frequency stimulation applied in modified medium differs in
      several respects from the LTP induced in standard conditions. They confirm that
      LTP is expressed to a markedly different degree by NMDA and non-NMDA receptors
      and suggest that events that do not necessarily accompany LTP affect the
      potentiation of NMDA receptor-dependent synaptic responses.

PMID- 1364047
TI  - Effects of chronic alcohol consumption and withdrawal on the somatostatin
      immunoreactive neurons of the rat hippocampal dentate hilus.
AB  - Previous studies have demonstrated that the dentate granule and the CA3 pyramidal
      cells of the rat hippocampal formation are neuronal populations vulnerable to the
      toxic effects of ethanol. It also has been shown that the resulting alterations
      do not end after withdrawal from ethanol. As the neurons in the dentate hilus are
      heavily interconnected with the dentate granule cells, the authors decided to
      examine the fate of the hilar neurons after chronic alcohol consumption and
      withdrawal, inasmuch as the hilar somatostatin-immunoreactive (SS-I) neurons were
      found to be sensitive to cerebral ischemia and to seizures. The following groups
      of adult rats were studied: (1) alcohol-fed for 6 and 12 months; (2) alcohol-fed
      for 6 months and then switched to water for a further 6 months; (3) pair-fed
      controls; and (4) controls fed ad libitum. The authors determined the numerical
      density of hilar neurons and the number of its SS-I subpopulation. These were
      found to be significantly reduced in both the alcohol-fed and withdrawal groups
      when compared with the respective age-matched controls. The consequent loss of
      the integrative action of the hilar neurons, including the SS-Is, could explain
      some of the alcohol-related functional deficits as well as their persistence
      after withdrawal.

PMID- 1364048
TI  - Characterization in vivo of the NMDA receptor-mediated component of dentate
      granule cell population synaptic responses to perforant path input.
AB  - The NMDA receptor-mediated component of the hippocampal granule cell population
      excitatory postsynaptic potential response to low frequency (< 0.2 Hz)
      stimulation of the medial perforant path was characterized in vivo. Extracellular
      recordings were obtained from the dentate molecular layer in anesthetized
      rabbits, and glutamatergic and GABAergic antagonists were applied locally by
      pressure ejection. To measure the NMDA-mediated component, the NMDA receptor
      antagonist D-5-aminophosphonovalerate (APV) was applied during the constant
      ejection of physiological saline, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX),
      and/or bicuculline methiodide. In general agreement with the results of attempts
      by other investigators to identify NMDA responses in vivo, APV did not
      significantly reduce the response to a single stimulus impulse in the presence of
      saline. However, an NMDA-mediated response was revealed when alpha-amino-3
      hydroxy-5-methyl-4-isoxazoleproprianate receptor-mediated current flow was
      eliminated by applying the non-NMDA receptor antagonist CNQX. The NMDA component
      was negative-going as predicted, but its duration was considerably less than
      indicated in other studies of the dentate in vitro. The relative magnitudes of
      the NMDA and non-NMDA components of the EPSP were found to vary as a function of
      stimulus intensity or frequency. The NMDA receptor-mediated component represented
      12% of the control response and increased to over 25% in response to higher
      stimulus intensities. A brief, high-frequency burst of impulses evoked a larger
      NMDA component in the presence of CNQX and was able to evoke an NMDA component in
      the presence of saline. Surprisingly, short trains of stimulation at lower
      frequencies typically produced suppression of the NMDA component. In a final
      series of experiments, it was found that many characteristics of the NMDA
      component were substantially altered by GABAergic inhibition. In the presence of
      the GABAA antagonist bicuculline, the magnitude of NMDA receptor-mediated
      responses was increased and their duration was greatly extended. Additionally, in
      the presence of bicuculline, the NMDA component facilitated markedly in response
      to frequencies of stimulus input > 20 Hz. These results indicate in vivo that the
      initiation and duration of NMDA current flow depend strongly upon the intensity
      and frequency of perforant path stimulation. In addition, the NMDA response to a
      single impulse appears to be reduced and truncated by input from GABAA receptor
      mediated feedback and/or feedforward inhibition, and this inhibition affects
      temporal summation of NMDA receptor-mediated responses over a wide range of input
      frequencies. It is suggested that such inhibition results from the activation of
      GABAA receptors located on granule cell dendritic shafts.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1364049
TI  - Species identification of spiny lobster phyllosome larvae via ribosomal DNA
      analysis.
AB  - Within the tropical northwestern Atlantic, Panulirus argus, P. guttatus, and P.
      laevicauda (Palinuridae family), are sympatric. Numerous studies have examined
      the distribution and abundance of planktonic phyllosome larvae with respect to
      recruitment of spiny lobsters to the benthic population, but the data are of
      limited use because larvae of these species cannot yet be distinguished from one
      another by morphological characteristics. A simple molecular method that
      unambiguously differentiates adults or larvae of P. argus, P. guttatus, and P.
      laevicauda is described: a 5' region of 28s ribosomal DNA is amplified in vitro
      and then cut with a diagnostic restriction enzyme to identify each species. Data
      are also presented from the application of this method to representative plankton
      tows.

PMID- 1364050
TI  - [New analogs of deoxyadenosine for treatment of lymphoid malignancies].

PMID- 1364052
TI  - Transfusion medicine: fact and fiction.

PMID- 1364051
TI  - Diagnostic value of ophthalmologic findings in myotonic dystrophy: comparison
      with risks calculated by haplotype analysis of closely linked restriction
      fragment length polymorphisms.
AB  - To determine diagnostic value of lens opacities in myotonic dystrophy (DM), we
      examined 98 at-risk members of 9 DM kindreds. Haplotype analysis of restriction
      fragment length polymorphisms (RFLPs) using ApoC2, CKMM, and pEFD4.2 supported
      the diagnosis of DM in 33 and excluded the diagnosis in 51 members. The
      sensitivities of bilateral iridescent lens opacities, posterior cortical lens
      opacities, orbicularis oculi weakness, low intraocular pressure, ptosis, and
      ocular myotonia were 46.7, 50.0, 60.6, 59.3, 51.5, and 3.0%, while their
      specificities were 100.0, 100.0, 98.0, 94.1, 96.1, and 100.0%, respectively. A
      peripheral pigmentary degeneration and central macular lesions of retina were not
      found on indirect fundoscopy. In 86.2% of DM patients, bilateral iridescent lens
      opacities, posterior cortical lens opacities, or both were present. Unilateral
      iridescent lens opacities occurred in only 3 of our DM patients, and 2 of non-DM
      relatives showed a few unilateral iridescent particles. Posterior cortical lens
      opacities in DM patients always affected both eyes in this series. We conclude
      that 1) bilateral iridescent lens opacities and posterior cortical lens opacities
      are highly specific for DM and useful for establishing clinical diagnosis of DM,
      2) unilateral iridescent lens opacities are infrequent in DM and are seen in some
      non-DM members, and 3) ocular myotonia and clinical retinopathies are rare in DM.

PMID- 1364053
TI  - Seasonal distribution and diel biting patterns of culicine mosquitoes in Costa
      Marques, Rondonia, Brazil.
AB  - A study of peridomestic man-biting culicines in the Amazon Basin was conducted
      from January through December, 1987. Fifteen species of mosquitoes from six
      genera were collected by volunteers in all-night human-bait indoor and outdoor
      collections at five houses in and near the town of Costa Marques, Rondonia,
      Brazil. Culex quinquefasciatus and members of the Mansonia titillans/indubitans
      Group comprised 61 and 33%, respectively, of all culicines collected from human
      bait outside houses and 62 and 35%, respectively, of those collected from
      volunteers inside houses in the town. In rural areas, Cx. quinquefasciatus was
      less abundant and only comprised 2 and 5% of the culicines, respectively,
      collected inside and outside houses. Mansonia titillans/indubitans Group
      comprised 75% and 86% of the culicines collected inside and outside houses,
      respectively, from rural residences. Culex quinquefasciatus and members of the
      Mn. titillans/indubitans Group were more endophilic than other culicines
      collected. Nocturnal and seasonal biting rhythms for the more common culicines
      are described.

PMID- 1364054
TI  - Molecular and biological diversity of HIV-1 in Brazil.
AB  - To determine the genomic polymorphism and biological properties present in HIV-1
      Brazilian isolates, we analyzed five viral isolates obtained from patients
      residing in Rio de Janeiro (P1 and P5), Sao Paulo (P3) and Bahia (P2 and P4)
      states. For each viral isolate in vitro characteristics such as replication rate,
      syncytium-inducing capacity and cell death were observed in lymphoblastoid (H9,
      CEM and peripheral blood mononuclear cells) as well as monocytoid (U937) cells.
      In addition, the evaluation of the restriction fragment length polymorphism of
      these isolates was also performed using a panel of endonucleases such as Hind
      III, Bgl II, Sac I, Pst I, Kpn I and Eco RI. One of the isolates (P1), showed the
      highest phenotypic and genotypic divergence, when compared to others. The results
      found suggest a HIV heterogeneity in Brazil similar to that already described in
      other regions of the world.

PMID- 1364055
TI  - Renal cell tumors induced in CBA male mice by 1,2-dimethylhydrazine.
AB  - Epithelial kidney tumors induced in CBA male mice by 1,2-dimethylhydrazine (DMH)
      were studied histochemically and immunohistochemically. A total of 48 tumors
      studied histologically were diagnosed as clear-cell, acidophilic, or mixed
      adenomas located in the renal cortex. Gamma-glutamyl transpeptidase (GGT) was
      strongly positive in normal proximal convoluted tubules, slightly positive in the
      cells of Bowman's capsule, and negative in 47 of 48 tumors examined. Antibodies
      against the new antigen obtained from the mouse liver oval cells, antigen A6,
      were also used. This antigen is negative in normal kidney proximal tubules but
      always positive in distal tubules and collecting ducts. It was also positive in
      all 47 GGT-negative tumors studied here. One tumor was GGT-positive and antigen
      A6-negative. Based on our data, it was concluded that the majority of renal cell
      adenomas induced by DMH in mice probably originate from the distal tubules or
      collecting ducts and not from the proximal tubules.

PMID- 1364056
TI  - Correlation of cardiovascular and respiratory responses to glutamate excitation
      of pressor areas of the medulla in cats.
AB  - Cardiorespiratory responses, including changes of systemic arterial pressure
      (SAP), renal or splanchnic sympathetic nerve activity (SNA) and phrenic nerve
      activity (PNA), were elicited by microinjection of monosodium glutamate solution
      (0.5 M, 100 nl) into the dorsal (DM) and rostral ventrolateral medulla (RVLM) in
      15 vagotomized cats anesthetized by urethane-chloralose and paralyzed by
      gallamine triethiodide. Artificial ventilation was adjusted to keep the end-tidal
      CO2 concentration at 4.0-0.5%. Sixty two pressor and 17 non-pressor sites were
      stimulated. Most of the stimulations inhibited the PNA. The responses of SNA was
      variable, showing increases, decreases or no change. Inhibition of SNA during SAP
      increase was not secondary to baroreceptor activation as the inhibition persisted
      in carotid sinus/aortic denervated animals. Although various combinations of
      changes of SNA and PNA were observed, their temporal courses were similar in many
      instances. Attenuation of SNA and PNA was synchronized, suggesting that these
      changes are coupled in the stimulating sites. The findings suggest that some
      neurons in DM and RVLM act as a functional unit to modulate cardiorespiratory
      functions whereas others simply coexist in the same area independent from each
      other.

PMID- 1364058
TI  - Age-related effects of MPTP on norepinephrine concentrations of various areas of
      rat brains.
AB  - The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the
      norepinephrine (NE) levels of 11 areas of rat brains were investigated. Male Long
      Evans rats, aged 4 weeks (young group) and 21 months (old group), were injected
      intraperitoneally (i.p.) with MPTP (3 mg/kg) daily for 8 days. Control rats
      received an i.p. injection of saline. Rats were sacrificed 24 h after the last
      injection. NE in various brain areas were assayed by high pressure liquid
      chromatography with electrochemical detection. Multidose treatment of MPTP caused
      no alteration of levels of NE in any brain area of young rats. In contrast, a
      marked increase in concentration of NE was found in locus coeruleus, dorsal raphe
      nuclei and amygdala of old rats. These results indicate that MPTP selectively
      causes lesions in the noradrenergic system of rats and that the neurotoxic
      effects of MPTP in rats may depend on age.

PMID- 1364057
TI  - Comparative studies of the neurotoxicity of MPTP in rats of different ages.
AB  - The present study investigated the neurotoxic effects of repeated MPTP injections
      on monoamine neurotransmitters and locomotor activity in rats of different ages.
      We also examined the mortality of MPTP-treated rats at different ages. Male
      Sprague-Dawley rats were used in all experiments. In the first experiment, we
      examined the mortality of rats (11-12 month old) subject to different doses of
      MPTP. In the second experiment, rats of 2-3 months old were randomly divided into
      five groups. Group 1 served as the control; Groups 2,3,4 and 5 received daily
      MPTP injections (30 mg/kg, ip) for a continuation of 7 days. Biochemical and
      behavioral assays were conducted at 1,7,14 and 28 days after withdrawal of MPTP,
      respectively. In the third and fourth experiments, the same experimental design
      was adopted except that rats of 5-6 months old and rats of 11-12 months old were
      used, respectively. Besides, the doses of MPTP used were 22.5 mg/kg and 12.5
      mg/kg, respectively. Immunohistochemical experiments were always conducted 7 days
      after withdrawal of MPTP. Results indicated that, in young rats, repeated MPTP
      injections did not significantly decrease DA, and 5HT levels as well as TH and
      DBH immunoreactivities although it impaired locomotor activity. The same
      treatment significantly depleted DA, NE and 5HT levels in the middle-aged rats.
      It also decreased the density of TH and DBH immunoreactivities and altered the
      morphology of DA and NE neurons. Meanwhile, it impaired locomotor activity. In
      old rats, MPTP injections produced effects similar to those observed in the
      middle-age rats except that the hippocampal serotonergic system was also
      affected. However, all these effects recovered 28 days after withdrawal of MPTP
      injection. Finally, the dose of MPTP required to exert similar extent of
      neurotoxicity decreased as the age of rats increased, and the dose required to
      result in mortality markedly decreased in old rats. These results together
      suggest that MPTP does exert a toxicity on DA, NE and 5HT neurons and impair
      motor activity in rats. These effects are age-dependent while the irreversibility
      of MPTP's toxicity in rats requires further investigation.

PMID- 1364059
TI  - Amyloidoses of the nervous system in the transmissible dementias.
AB  - The transmissible spongiform encephalopathies, both in humans and in animals, are
      neurodegenerative diseases which do not evoke an immune response in the host. The
      search for the etiological agent has led to the prion hypothesis, which proposes
      that a host-encoded protein may be the causal agent itself or a part of it. In
      humans, a low percentage of these transmissible encephalopathies are familial.
      Investigations centered on the understanding of the pathogenesis of the
      transmissible spongiform encephalopathies have implications, not only in basic
      sciences, but in clinical medicine as well.

PMID- 1364060
TI  - Transgene transmission and expression in rainbow trout and tilapia.
AB  - We describe the production of transgenic rainbow trout (Oncorhynchus mykiss) and
      tilapia (Oreochromis niloticus) by microneedle injection of fertilized eggs with
      cloned copies of novel gene constructs. Two aspects of the work with transgenic
      trout are presented; namely, patterns of inheritance of transgenes by the F1
      generation following in vitro fertilization of gametes from transgenic and
      nontransgenic fish, and the degree of DNA methylation of transgenes in different
      fish and in different tissues of the same fish. Work with transgenic tilapia has
      been only of short duration, and evidence is presented simply to indicate their
      transgenic status. Transient expression studies using the bacterial gene
      chloramphenicol acetyltransferase when driven by fish-derived promoters are also
      discussed.

PMID- 1364061
TI  - [Torsades de pointes during sultopride poisoning].
AB  - A case of sultopride poisoning (ingested dose 16 g) in a 35-year-old, 65 Kg man
      is described. On admission myoclonus, mydriasis, vomiting and cardio-respiratory
      arrest were observed. Torsades de pointes were treated with potassium chloride
      infusion and pace maker stimulation. Plasma sultopride concentration was 25 mg/l
      and urinary concentration 12 g/l. A prolongation of Q-T interval may announce
      severe arrhythmias in sultopride poisoning.

PMID- 1364062
TI  - Twenty-four-hour intragastric pH-metry: H2-receptor antagonist restoration of
      nightly gastric spontaneous alkalinization in duodenal ulcer healing.
AB  - Continuous 24-hour intragastric pH monitoring allows the evaluation of
      spontaneous late night gastric alkalinization phenomenon (SNA). This nocturnal
      increase of intragastric pH is strongly evident in healthy volunteers but is
      insignificant in patients with active duodenal ulcer. Gastric acidity was
      monitored by 24-hour continuous pH-metry in nine patients with active duodenal
      ulcer disease before and after two weeks of therapy with ranitidine. A twice
      daily dose of the drug (150 mg at 08.00 h and 150 mg at 20.00 h) was orally
      administered to each subject. Before treatment the ulcer patients did not show
      the SNA phenomenon, but the therapy led it to reappear. Ranitidine significantly
      reduced the time during which the gastric acidity was lower than 4 pH units;
      moreover the drug was effective on the ulcer healing during a period as brief as
      two weeks of therapy. At least a complete healing of the duodenal ulcer could be
      seen in patients whose overall gastric acidity time was reduced almost to the 40%
      of the pre-treatment value, meal times excluded from the pH-metric calculation.

PMID- 1364063
TI  - [Magnesium oxide and tocolysis. Our clinical experience and comparison with beta
      mimetic (isoxusprine) therapy].
AB  - The authors propose the use of oral Magnesium Oxide in the quantity of 200 mg
      every 3-4 hours for the tocolytic treatment of the pre-term pain, once
      intravenous tocolysis has decreased or stopped uterine activity (since it has
      considerably more rapid effect). This treatment constitutes a valid alternative
      to the use of Beta Mimetic agents in all cases where their use is
      contraindicated. In the present study, we followed one heterogeneous group of 130
      patients, suffering from premature labor hospitalized in our department. After
      decreasing the uterine contractions by intravenous isossuprine, sixty patients
      were subsequently treated with magnesium Oxide, fifty with oral isossisuprine,
      twenty with a simple antispasmodic and the remaining constituted the control
      group. The percentage of pre-term births has been almost the same in the first
      two groups (around 17%). The percentage of the patients who exhibited side
      effects of Beta Mimetic was 30-40%, against 2% of the patients treated with
      Magnesium Oxide. The intensity of the symptoms was however so slight in the
      patients treated with Magnesium Oxide, that it failed to disturb the compliance
      of the patients which allowed to continue the therapy for the necessary period.

PMID- 1364066
TI  - Spasmodic torticollis: medical and botulinum A toxin treatment.
AB  - The exact pathophysiologic mechanisms of spasmodic torticollis and other
      idiopathic torsion dystonias remain largely unknown. Thus, a variety of drugs
      have been used alone or in combination on an empirical basis to treat these
      disorders, but to date none have efficacy that is proven and consistent. The
      drugs in use include anticholinergics, benzodiazepines, dopaminergics and
      dopamine antagonists with variable degrees of clinical improvement. Botulinum
      toxin A injection treatment for spasmodic torticollis is safe and efficacious
      with minimal adverse effect. However, it is expensive and beneficial effects are
      short-lasting. Only when a spasmodic torticollis patient's symptoms are
      refractory to combined treatment, using various drugs and Botulinum toxin
      injections, should the patient be considered a candidate for neurosurgical
      procedures.

PMID- 1364067
TI  - Plasminogen Activation in Fibrinolysis, in Tissue Remodeling, and in Development.
      Proceedings of a conference. Leiden, the Netherlands, October 22-25, 1991.

PMID- 1364064
TI  - [Rheumatoid arthritis in Morocco. Apropos of 404 observations].
AB  - A retrospective study of 404 cases of rheumatoid arthritis seen in a department
      of internal medicine in Casablanca highlights a number of specific features of
      the disease in Morocco. Onset occurred early and mean age of patients was 34.4
      years. Analysis of joint manifestations showed that the disease tended to be mild
      in the hips and perhaps in the cervical spine. Thirty-five percent of patients
      were Steinbrocker's class II and 25.5% had carpal bone fusion. Only 20 patients
      had severely erosive disease, which manifested as giant geodes in 8 cases and as
      main en lorgnette deformity in one case. Subcutaneous nodules (7.9%) and systemic
      visceral disorders were fairly infrequent. Only three cases of malignant
      rheumatoid arthritis were found. Gougerot-Sjogren syndrome was present in 13.6%
      of patients. Among comorbid conditions, thyroid gland diseases and tuberculosis
      were fairly common. Serologic tests were positive in 61.14% of cases, often in
      low titres. Gold salt therapy was well tolerated. No patients in this group had
      surgical treatment. These data suggest that in Morocco rheumatoid arthritis may
      be less aggressive than in Europe.

PMID- 1364065
TI  - Homing of liver-derived hemopoietic stem cells to fetal bone marrow.
AB  - Tissue distribution of HSC in fetal sheep was studied by in utero transplantation
      during the period when a switch in the site of hemopoiesis occurs from
      liver/spleen to the bone marrow. At day 50 of gestation, transplanted cells
      exclusively homed to the liver/spleen. By day 60, some HSC also homed to the
      marrow and, between days 60-80, their proportion in the marrow increased. By day
      100 almost all engrafted donor HSC homed to the marrow. Nonetheless, expression
      of these stem cells did not occur in the blood until birth (day 145) when marrow
      assumed the function of hemopoiesis from liver/spleen. During this latter part of
      gestation, although homing sites in the marrow are available to transplanted HSC,
      the marrow does not contribute to the function of hemopoiesis. The significance
      of these observations in the context of in utero gene therapy via stem cell
      transplantation is discussed.

PMID- 1364068
TI  - Mucosal plasminogen activator activity in peptic ulcer disease.

PMID- 1364069
TI  - Extended Clinical Consulting by Hospital Computer Networks. Proceedings of a
      conference. Boston, Massachusetts, March 22-25, 1992.

PMID- 1364070
TI  - [The Intercounty Symposium on Pneumology, Brad, Hunedoara County, 24-25 September
      1992. Round table on the topic: "Care for chronic nontubercular lung patients.
      The present situation and the future directions of the pneumophthisiology network
      in Hunedoara County"].

PMID- 1364071
TI  - [New viewpoints on therapy with beta-2-agonist-type bronchodilators and
      corticosteroids in bronchial asthma].

PMID- 1364072
TI  - Inhibitory role of somatostatin on calcitonin secretion.
AB  - Calcitonin (CT) secretion is not exclusively controlled by calcemia, but the
      secretory tonus is maintained by the beta-stimulatory adrenergic system
      Somatostatin (SMS) plays a neuromodulatory role with the reduction of CT
      secretion by its interference at the central and peripheral level of the beta
      adrenergic receptors. The experiments were carried out on groups of rats in which
      the effect of SMS on CT content of the thyroid gland was followed up. Thus, SMS
      administered i.c.v. significantly reduced the basal CT secretion without blocking
      the stimulatory effect of calcium. The results were comparable with those
      obtained after the blockade of the sympatho-adrenergic system by chemical
      sympathectomy with 6HODA or propranolol. Central blockade of alpha receptors with
      phentolamine determined a significant rise of CT. This effect was annihilated by
      SMS. The i.v. administration of SMS did not induce a change in CT content of the
      thyroid, but blocked the stimulatory action of hypercalcemia. The results are
      identical with those obtained by blocking the beta-receptors with propranolol.
      SMS also blocked the stimulatory effects of isoproterenol on CT secretion. The
      data obtained revealed the fact that SMS lowers CT secretion by the central and
      peripheral interference of the sympatho-adrenergic path, maintaining the
      secretory tonus of the thyroid C cells.

PMID- 1364073
TI  - Molecular biology for platelet alloantigen typing.
AB  - Hitherto, full investigation of patients with alloimmunization to platelet
      specific antigens has been difficult due to the limited availability of both
      typing reagents and panels of typed platelets. Following recent advances in the
      understanding of the molecular and genetic basis of platelet alloantigens, it is
      now possible to genotype individuals for the alleles coding for the epitopes of
      four platelet antigen systems (HPA-1-4). This is based on the finding that the
      two alleles differ by only a single base pair substitution, resulting in one
      amino acid difference in the relevant platelet glycoprotein. The technique
      involves amplification of the relevant segments of genomic DNA from any nucleated
      cell by the polymerase chain reaction, followed by restriction fragment length
      polymorphism analysis. The technique allows investigation of thrombocytopenic
      individuals and fetuses/neonates, and can be readily applied to large-scale
      typing of platelet donors.

PMID- 1364074
TI  - [Effects of four adrenergic drugs on electroacupuncture analgesia].
AB  - The role of central nor-epinephrine (NE) in electroacupuncture (EA) analgesia is
      a controversial question., it is probably due to the complication of adrenergic
      receptors. The present results show: (1) Clonidine 30 micrograms/2ml/kg ip had no
      significant effect on the pain threshold, but decreased the analgesic effect of
      EA. Clonidine 1.5 and 3 micrograms were injected into the lateral cerebral
      ventricles. After 45 minutes, the analgesic effect of EA was lowered as compared
      with the saline controls respectively. (2) Yohimbine had no significant effect on
      the basal pain threshold, but (icv Yoh 50 micrograms) elevated the analgesic
      effect of EA. (3) 2-adrenoceptor agonist methoxamine decreased the analgesic
      effect of EA. (4) Another 2-adrenoceptor antagonist prazosin (icv 16 micrograms)
      enhanced the analgesic effect of EA. These results suggest that an activation of
      alpha 1- or alpha 2-adrenoceptors would decrease the analgesic effect of EA.

PMID- 1364075
TI  - Guanylyl cyclases: ligands and functions.

PMID- 1364076
TI  - Each caveola contains multiple glycosyl-phosphatidylinositol-anchored membrane
      proteins.

PMID- 1364077
TI  - Summary: the cell surface regulates information flow, material transport, and
      cell identity.

PMID- 1364078
TI  - [A critical study of conditions for prescription and evaluation criteria of
      neuroleptic treatment in resistant schizophrenia].
AB  - From the study of Kane et al. (1988), devoted to clozapine, a critical analysis
      of criteria of assessments about studies in treatment of resistant schizophrenic
      patients was drawn up. Therefore, among the inclusion criteria, the authors
      strengthen the necessity of a very long past neuroleptic treatment (beyond six
      months) before diagnosing a resistance, the "drug-free improvers" characterized
      by improvement when patients had been treated by a placebo, the necessity of a
      very long placebo wash-out (beyond six weeks), and the improvement by a second
      treatment after a first ineffective treatment. Moreover, the doses of
      neuroleptics opposed to clozapine are often too high leading to adverse effects
      and so decreasing the positive benefits. For instance, the dose of chlorpromazine
      is often increased to 1,800 mg/day whereas the doses required should be only 600
      mg/day in equivalence to 500 mg/day of clozapine. Lastly, the scales more
      specific of the symptomatology of schizophrenia such as SANS-SAPS or PANSS should
      be used in the clinical trials whereas until now, all the studies were made by
      standard and global evaluations with BPRS, CPRS and AMDP.

PMID- 1364079
TI  - [The atypical neuroleptic concept].
AB  - Atypical neuroleptics can be defined as dopamine (DA) receptor blockers which
      differ from typical neuroleptics in that they have a markedly lower or absent
      propensity for the induction of parkinsonian side effects of tardive dyskinesias.
      Some of them, but not all, are also more effective in treating schizophrenic
      patients, i.e. those with negative symptoms or who resist to classical
      treatments. There may be four classes of potential atypical neuroleptics: 1)
      Antipsychotics such as sulpiride and remoxipride that block a subgroup of D2
      receptors; 2) D1 antagonists that may prove to be a valuable new type of
      antipsychotic drug; 3) Partial D2 agonists and 4) Antipsychotics such as
      clozapine and risperidone which block DA as well as other receptors and which
      appear to have the most pronounced antipsychotic effect. The differences between
      typical and atypical neuroleptics may first relate to regional specificity in
      site of actions. Animal studies suggest that atypical neuroleptics may act
      preferentially on mesolimbic and mesocortical as opposed to striatal DA systems.
      Most studies which have attempted to define the biological mechanisms which
      subserve the differences between atypical and typical neuroleptic drugs have
      focused on receptor binding profile of these drugs. Relatively higher affinity
      for the serotonin (5HT2) receptor than for the D2 receptor may be important to
      the action of clozapine-like compounds. However, many other systems might be
      involved and it seems likely that the atypical neuroleptic profile could be
      achieved in more than one way.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364080
TI  - [Use of pharmacological data in the choice of antipsychotic drugs].
AB  - The choice of antipsychotic drug should be based on experimental data from
      biochemistry and animal pharmacology, according to the targeted clinical effects.
      However, owing to the lack of good animal models of mental disease only the
      clinical approach can validate the antipsychotic efficacy of a drug. Within the
      theoretical frame of dopaminergic activity in schizophrenia a specificity of the
      various neuroleptics according to the four dopaminergic structure is evidenced
      through cellular electrophysiological studies. Classical provisional pharmacology
      of antipsychotics uses in animals on the one hand naturalistic observation tests,
      and on the other hand interactions vis-a-vis behaviours induced by stimulating
      dopaminergic agents, as amphetamine and apomorphine. Differential analysis of
      antipsychotic effects on each of those behaviours allows to discriminate between
      the various neuroleptics and to refine their pharmacological profile, specially
      to predict a disinhibitory action with some of them. Progress in the
      identification, localisation, number modification of target receptors of
      different neurotransmitters as well as the biochemical response to their
      stimulation by agonist or antagonist allows to delineate more precisely the
      neurobiochemical action of antipsychotic drugs. On top of antidopaminergic D2
      effect, anti D1 effect begin to be investigated. More over the role of
      antiserotonergic 5-HT2 and central anticholinergic actions seems to be important
      in the "atypical" aspect of some neuroleptic drugs. More recently, contributions
      from molecular biology made it possible to clone and to synthetize five subtypes
      of dopaminergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364081
TI  - Effects of the medium chain octanoic fatty acid on the contractile activity of
      vascular smooth muscle tissues.
AB  - Multiple elevation of the octanoic fatty acid level in human sera is often
      observed in some hepatic diseases which are accompanied by cardiovascular
      disorders, hypotension, and increased cardiac stroke volume. Different
      experiments reveal the hypotensive effect of octanoate. The present study
      investigates the octanoate action on the bioelectric and contractile activity of
      vascular smooth muscle tissues. Octanoate is shown to cause hyperpolarization of
      smooth muscle cells, reduction of spike potential frequency, and relaxation of
      vascular muscles. These effects are inhibited by indomethacin, which proves their
      prostaglandin nature. Octanoate action on stomach smooth muscle strips is
      inhibited by SC 19220, a specific competitive inhibitor of the contractile action
      of prostaglandins E2 and F2 alpha on the same tissues in vitro. Using thin-layer
      chromatography two PG fractions were isolated from arterial blood of octanoate
      treated rats and from a control group of rats. These fractions have identical
      chromatographic characteristics with those of PGE2 and PGF2 alpha. The level of
      the PG fraction with Rf value similar to that of PGE2 is significantly increased
      in octanoate treated animals while the other fraction tends to decrease.

PMID- 1364082
TI  - Mechanisms of neurotransmission of valproate sodium in suppressing barbiturate
      and phenytoin withdrawal syndrome.
AB  - The present study was undertaken to investigate some important processes of
      neurotransmission which occur in rat brains under the influence of valproate
      sodium. Valproate sodium is used for the suppression of the withdrawal effects
      resulting from sudden discontinuation of phenobarbital and phenytoin treatment.
      Corpus striatum, hippocampus and cortex were isolated operatively. The amounts of
      neuromediators (dopamine, noradrenaline, serotonin and gamma-aminobutyric acid)
      were determined using fluorometry. The results show that the anti-withdrawal
      effect of valproate sodium established in previous research probably is due to
      active metabolites which increase the amount of gamma-aminobutyric acid in all
      brain structures. In suppressing barbiturate and phenytoin withdrawal syndrome
      using valproate sodium, the previously established anti-withdrawal effect
      probably is due to high tissue levels of dopamine in hippocampus and to
      noradrenaline in the cortex, hippocampus and corpus striatum. This anti
      withdrawal effect continues for three days after the discontinuation of valproate
      sodium. This probably is due to the accumulation of the inhibitory neuromediator
      GABA in the cortex, hippocampus and corpus striatum and to the elevated level of
      dopamine in hippocampus. The results raise new possibilities for developing
      medicinal substances, which possess anti-withdrawal action, from the metabolites
      of the valproate sodium.

PMID- 1364083
TI  - [Effect of denopamine on residual left ventricular dysfunction after complete
      revascularization].
AB  - Denopamine (15 mg/day) was administered to 20 patients with residual left
      ventricular dysfunction after successful percutaneous transluminal coronary
      angioplasty (75% or more diameter stenosis). Echocardiography was performed
      before and 6 months after denopamine administration to analyze the left
      ventricular function. There were significant decreases in both end-diastolic and
      end-systolic dimensions from 58 +/- 8.3 to 54 +/- 8.4 mm (p = 0.001), and from 44
      +/- 10.1 to 40 +/- 10.3 mm (p = 0.005)), respectively, while % fractional
      shortening remained nearly constant (from 25 +/- 8.3 to 27 +/- 9.6%). Thus,
      denopamine improved the left ventricular function by decreasing left ventricular
      size while maintaining wall contractility.

PMID- 1364084
TI  - Disturbed testicular descent in the rat after prenatal exposure to the
      antiandrogen flutamide.
AB  - Exposure of rats in utero to the anti-androgen flutamide resulted in feminization
      of the external genitalia that was noticeable at birth. This exposure also
      resulted in a high degree of cryptorchidism during adulthood. In most affected
      animals, testes were lying in 'ovary position' close to the caudal pole of the
      ipsilateral kidney. Cryptorchidism occurred despite normal prenatal development
      of the gubernacular cones and the transformation of these structures,
      postnatally, into muscular cremaster sacs. Inter- and intralitter variation in
      the response to prenatal exposure to flutamide was observed as well as intra
      individual variation. Cryptorchidism frequently occurred unilaterally with right
      side cryptorchidism predominating. Cryptorchidism occurred in association with
      marked suppression of the growth of the ipsilateral epididymis and deferent duct.
      The possibility is considered that the poor development or absence of these
      structures contributes to cryptorchidism. Intra-individual variation supports the
      concept of the local nature of the influence of testis hormones in stabilization
      and further differentiation of the ipsilateral Wolffian duct derivatives.
      Cryptorchidism was enhanced when rats were treated postnatally with testosterone
      or oestradiol. The effect of testosterone was unexpected in view of the generally
      held hypothesis that androgens enhance testis descent. The effect of oestradiol
      was as expected: other animal models have been described in which induction of
      cryptorchidism by oestradiol occurs. Additional treatment with oestradiol caused
      further suppression of growth of the epididymis and deferent duct. The response
      to prenatal exposure to flutamide was not altered by further injections of
      flutamide postnatally. Such injections were without effect in males not exposed
      to flutamide prenatally except for minor, but statistically significant,
      testicular enlargement during adulthood. A model is thus presented that describes
      cryptorchidism as an endogenous developmental disorder.

PMID- 1364085
TI  - Bovine spongiform encephalopathy (BSE): a stimulus to wider research.
AB  - The severity of the epidemic of bovine spongiform encephalopathy which is
      currently afflicting cattle in the British Isles has stimulated a considerable
      research effort, much of which is directed toward understanding the aetiology and
      pathogenesis of the bovine disease. However, a significant thrust has also been
      orchestrated to address more fundamental issues such as the nature of the
      uncharacterized causal agents of the wider range of unusual animal and human
      diseases which share similar characteristics. The background to some of these
      research programmes is discussed, together with current aims and progress.

PMID- 1364086
TI  - [Restriction fragment length polymorphism of the 5'-region of the bovine
      ribosomal spacer repeat].
AB  - The restriction map of bovine 28S rRNA gene and adjacent 5'-spacer region was
      determined. The high level of intragenomic and population length polymorphism of
      EcoRI-BamHI restriction fragment was demonstrated to originated from the 3'-end
      of 28S rDNA and 5'-spacer of rDNA repeat. This polymorphism is more pronounced
      than the ones revealed in human and murine rDNA repeats and could be compared
      with genomic fingerprints obtained by M13 or minisatellite DNA hybridization
      probes. From family blot-panel analysis we concluded that in progeny only
      parental sets of length variants were inherited and that the copy number of
      definite variants does not change in the progeny as well. From these results it
      was proposed that the definite sets of linked in genome length variants are
      inherited independently from each other.

PMID- 1364087
TI  - A comparative study of gastrointestinal nematode egg output in N'Dama, Zebu and
      N'Dama x Zebu crossbred cattle.
AB  - Strongyle faecal egg output was estimated in N'Dama, Zebu and N'Dama x Zebu
      crossbred (F1) cattle. N'Dama cattle showed a significantly lower prevalence of
      strongyle infection, as measured by faecal egg output, than F1 (P < 0.01) and
      Zebu (P < 0.001) cattle. In strongyle-infected animals, mean egg output was also
      significantly lower in N'Damas (P < 0.03) than in Zebus. A previous
      trypanosomiasis infection did not affect the results. The presence of a natural
      resistance trait to strongyle infection in N'Dama cattle is postulated.

PMID- 1364088
TI  - [XVII National Congress of The Italian Society of Parasitology. Camerino, San
      Benedetto del Tronto, 27-31 July 1992. Abstracts].

PMID- 1364090
TI  - The presence of somatostatin receptors in malignant neuroendocrine tumor tissue
      predicts responsiveness to octreotide.
AB  - In 77 percent of patients suffering from a malignant carcinoid syndrome,
      administration of the somatostatin analog, octreotide (SMS 201-995, Sandostatin)
      induced clinical improvement coupled with a decrease in 24-hour urinary 5
      hydroxyindole acetic acid (5-HIAA). This finding prompted an evaluation to
      determine the correlation between the presence of somatostatin receptors in tumor
      tissue and the response to octreotide in patients with advanced, metastatic,
      neuroendocrine tumors. In tissues of 31 tumors (20 carcinoid, eight islet-cell
      carcinoma, three medullary thyroid carcinomas), the presence of somatostatin
      receptors was analyzed by binding of the somatostatin analog 125I-Tyr3-SMS 201
      995 and autoradiography. Receptors were detected in 16 of 20 samples of carcinoid
      tissues; all but one patient with receptor-positive tumors improved clinically
      after treatment with octreotide, and the urine 5-HIAA level was reduced a median
      of 63 percent (range, 39-94 percent) compared to values before treatment. Of the
      receptor-negative carcinoid patients, only one showed clinical improvement, which
      was minimal, and there was a negligible reduction in 5-HIAA after octreotide
      therapy. All eight patients with metastatic islet-cell carcinomas were positive
      for somatostatin receptors. Symptomatic improvement and a > 50 percent decrease
      in the level of at least one of the pathologically elevated marker hormones was
      seen in all eight. None of the three patients with medullary carcinoma of the
      thyroid had a decrease in calcitonin, and all three were initially somatostatin
      receptor-negative. We conclude that the presence of somatostatin receptors in
      malignant neuroendocrine tumor tissue appears to correlate with the response to
      octreotide therapy. Analysis of somatostatin receptors in malignant
      neuroendocrine carcinoma tissue should be included in future prospective clinical
      trials of this synthetic peptide.

PMID- 1364091
TI  - Regional differences in the contractile activity of neuropeptide Y, endothelin,
      oxytocin and vasopressin: comparison with non-peptidergic constrictors. An in
      vitro study in the basilar and mesenteric arteries of the rat.
AB  - The vasoconstrictor effect of the peptides neuropeptide Y (NPY), endothelin
      (ENDO), vasopressin (VPR) and oxytocin (OXY) (10(-11)-10(-7) M) was compared in
      the isolated basilar (BAS) and mesenteric (MES) arteries of rat. The contractile
      activity of these peptides was compared to that of three nonpeptidergic
      constrictors: noradrenaline (NA), serotonin (5-hydroxytryptamine, 5-HT) and
      prostaglandin F2 alpha (PGF2 alpha) (10(-8)-10(-4) M). As regards EC50 values,
      PGF2 alpha was equally potent in both vessels studied, 5-HT was more potent in
      BAS and NA was without contractile effect in BAS. Pronounced regional differences
      were found for the peptides studied. BAS was more sensitive in EC50 values to the
      peptides in the order ENDO > or = VRP > OXY > NPY. In MES, OXY and NPY caused no
      and VPR caused weak contraction, whereas the effect of ENDO was pronounced, with
      a similar EC50 value as in BAS. In conclusion, marked regional differences were
      found in response to contractile agents in the vascular beds studied. Peptidergic
      constrictor mechanisms might be of large importance in the regulation of cerebral
      blood flow during physiological or pathophysiological conditions.

PMID- 1364093
TI  - Use of an antisense RNA expression system to explore functions of PKC isoenzymes
      in T-cell activation.

PMID- 1364089
TI  - Factors controlling pancreatic islet neogenesis.
AB  - We have established a model in which cellophane wrapping induces reiteration of
      the normal ontogeny of beta-cell differentiation from ductal tissue. The
      secretion of insulin is physiologic and coordinated to the needs of the animal.
      Streptozotocin-induced diabetes in hamsters can be "cured" at least half the
      time. There appears to be activation of growth factor(s) within the pancreas,
      acting in an autocrine, paracrine, or juxtacrine manner to induce ductal cell
      proliferation and differentiation into functioning beta cells. Given the results
      of our studies to date, it does not seem premature to envisage new approaches to
      the treatment of diabetes mellitus. Identification of the factor(s) regulating
      islet-cell proliferation and differentiation in our model may permit islets to be
      grown in culture. This concept could be extended to induce endocrine cell
      differentiation in vitro as well. Furthermore, islet-cell growth factors could be
      used to provide "trophic support" to islet transplants as a means of maintaining
      graft viability. There may also be greater scope for gene therapy when the growth
      factor(s) have been isolated, purified, sequenced, and cloned.

PMID- 1364094
TI  - Liposomal delivery of antisense oligodeoxynucleotides. Application to the
      inhibition of the multidrug resistance in cancer cells.

PMID- 1364095
TI  - Chemical modifications to improve uptake and bioavailability of antisense
      oligonucleotides.

PMID- 1364092
TI  - Antisense Strategies. Proceedings of a conference. Philadelphia, Pennsylvania,
      January 12-15, 1992.

PMID- 1364096
TI  - Natural killer cell stimulatory factor (NKSF) or interleukin-12 is a key
      regulator of immune response and inflammation.
AB  - Natural Killer cell Stimulatory Factor (NKSF) or interleukin-12 (IL-12) is a
      heterodimeric cytokine of 70 kDa formed by a heavy chain of 40 kDa (p40) and a
      light chain of 35 kDa (p35). Although it was originally identified and purified
      from the supernatant of Epstein-Barr virus-transformed B cell lines, it has been
      shown that among peripheral blood cells NKSF/IL-12 is predominantly produced by
      monocytes, with lower production by B cells and other accessory cells. The most
      powerful inducers of NKSF/IL-12 production are bacteria, bacterial products and
      parasites. In addition to the biologically active p70 heterodimer, the cells
      producing NKSF/IL-12 also secrete a large excess of monomeric p40, a molecule
      with no demonstrable biological activity. NKSF/IL-12 is active on T lymphocytes
      and NK cells on which it induces production of lymphokines, enhancement of
      cytotoxic activity and mitogenic effects. NKSF/IL-12 induces T and NK cells to
      produce IFN-gamma and synergizes with other IFN-gamma inducers in this effect. In
      vitro, and probably in vivo, NKSF/IL-12 is required for optimal IFN-gamma
      production. When human lymphocytes are stimulated with antigens in vitro,
      addition of exogenous NKSF/IL-12 to the culture induces differentiation of T
      helper type 1 (Th1) cells, whereas neutralization of endogenous NKSF/IL-12 with
      antibodies favors differentiation of Th2 cells. IFN-gamma, a product of Th1
      cells, enhances NKSF/IL-12 production by mononuclear cells, whereas IL-10 and IL
      4, products of Th2 cells, efficiently inhibit it. Therefore, NKSF/IL-12 appears
      to be an important inducer of Th1 responses produced by accessory cells during
      early antigenic stimulation and its production is regulated by a positive
      feedback mechanism mediated by Th1 cells through IFN-gamma and a negative one by
      Th2 cells through IL-10 and IL-4. The balance of IL-12 production versus IL-10
      and IL-4 production early during an immune response might therefore be
      instrumental in determining Th1-type versus Th2-type immune responses. Because of
      this potential role of IL-12 during immune responses, our results demonstrating
      the impaired ability of HIV seropositive patients to produce NKSF/IL-12 in
      response to bacterial stimulation suggest that this defect in NKSF/IL-12
      production might be a factor contributing to their immune depression.

PMID- 1364098
TI  - XII Seminar on Amebiasis. Proceedings. Mexico City, Mexico, November 11-14, 1992.

PMID- 1364097
TI  - Psychosocial Aspects of Genetic Counseling. Proceedings of a conference. Leuven,
      Belgium, September 24-26, 1990.

PMID- 1364099
TI  - Differentiation of pathogenic Entamoeba histolytica from other intestinal
      protozoa by riboprinting.
AB  - Differentiation of the pathogen Entamoeba histolytica from the variety of other
      amebas that can infect the human intestinal tract is vital for accurate diagnosis
      and treatment. Morphology and serology alone are not adequate for positive
      identification to be achieved. We have developed methods using the polymerase
      chain reaction to amplify amebal ribosomal RNA genes that allow either specific
      detection of E. histolytica or species identification.

PMID- 1364100
TI  - Organization of repeated sequences in the region downstream to rRNA genes in the
      rDNA episome of Entamoeba histolytica.
AB  - The E. histolytica rDNA episome consists of a 3.7 kb HindIII fragment located
      downstream of the rDNA inverted repeats. We have determined the complete
      nucleotide sequence of this fragment and have shown that it is comprised of two
      families of short tandem repeats, the 170 bp DraI repeat and the 144 bp ScaI
      repeat. Each DraI repeat unit consists of 12-mer sequences with near complete
      homology to yeast consensus autonomously replicating sequence. In addition, a 21
      mer subrepeat structure is also present in each unit. The sequence of the ScaI
      repeat is about 90% homologous with the sequence of another family of 145 bp
      tandem repeats, the PvuI repeats reported to be present upstream of the rRNA
      genes (3). Compared with most other parts of the rDNA episome, the downstream
      region showed frequent restriction fragment length polymorphism. This was due to
      changes in the number of tandem DraI repeat units. The loss of these repeats
      might explain how rDNA length heterogeneity observed in the clones of HM1:IMSS
      could have arisen. On the other hand, the number of ScaI repeat units in these
      clones remained unchanged. The repeat units found in the 3.7 kb HindIII fragment
      show superficial resemblance to equivalent regions of the intergenic spacers of
      higher eukaryotes. Moreover, these repeated sequences seem to be specific for the
      pathogenic strain of E. histolytica.

PMID- 1364102
TI  - [Ciguatera in French Polynesian islands: of coral, fish and men].

PMID- 1364101
TI  - P-glycoprotein genes of Entamoeba histolytica.
AB  - Six different P-glycoprotein gene segments were identified from an emetine
      resistant E. histolytica mutant, which overexpresses mRNAs homologous to segments
      of the human mdr1 (P-glycoprotein) gene. The open reading frames of two
      completely sequenced genes EhPgp1 and EhPgp2 were 1,302 and 1,310 amino acids
      long, respectively, and showed a 67% positional identity with each other and 41
      and 40% positional identities, respectively, with human mdr1 gene. Within each
      ameba P-glycoprotein were the ATP-binding sites found twice in eukaryotic P
      glycoproteins and once in prokaryotic transport proteins. A phylogenetic tree
      showed that Entamoeba P-glycoproteins are more related to the human and mouse P
      glycoproteins than to the Plasmodium and Leishmania P-glycoproteins. In addition,
      there were two P-glycoprotein pseudogenes, each with a frame shift and stop
      codons in identical places within the amino ATP-binding site.

PMID- 1364103
TI  - Ciguatoxic fish in the French West Indies.
AB  - An epidemiological study on ciguatera fish poisoning in the French West Indies on
      St-Barthelemy, St-Martin and Anguilla was conducted in the years 1985-1986-1987
      and 1991-1992. A study on the toxicity of coral fish was realized. The toxicity
      of 700 fish belonging to 57 species was evaluated by bio-assays. 430 mosquito-bio
      assays were performed on individual fish (flesh or liver) and 19 on pools (flesh
      or liver; with 4 to 24 fish). A second group was evaluated on liver by the chick
      feeding-test (33 individual and 64 on pools with 2 to 24 fish). The results
      showed that many species are involved in the toxic food chain. At least 25% may
      have a high level of toxicity, 32.5% are intermediate and 10% are doubtful. Major
      results concern: (1) high risk species (Caranx bartholomaei, C. lugubris,
      Lutjanus apodus, L. jocu, Gymnothorax funebris, G. moringa, Mycteroperca
      venenosa, M. tigris, Epinephelus morio, Sphyraena barracuda); (2) intermediate
      species (Caranx latus, C. ruber, Lutjanus buccanella); (3) low risk species
      (Balistes vetula, Haemulon album, Priacantus arenatus, Alphestes afer).
      Occasionally other species or new species are involved Etelis oculatus, Lutjanus
      analis, Pristipomoides macrophtalmus, Rhomboplites aurorubens, Haemulon album,
      Scarus vetula.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364104
TI  - Evolution of Gambierdiscus toxicus populations in the coral reef complex of
      Mayotte Island (SW Indian Ocean) during the 1985-1991 period.
AB  - Evolution of the Gambierdiscus toxicus populations during the 1979/1985-1991
      period shows an increase of the average densities until 1988-Sept. that seems
      linked with climatic parameters (insolation, rainfalls) but mainly with
      anthropogenetic disturbances. After a bloom the populations are now stabilized at
      a level higher than at the beginning of the monitoring. Without clear
      correlation, Gtx densities seems associated to physical and chemical features of
      the lagoonal and reefal waters.

PMID- 1364105
TI  - Are Streptomyces bacteria involved in the ciguatoxicity of the surgeon fish
      Ctenochaetus striatus?
AB  - Several Streptomyces strains have been isolated from the digestive tract of the
      herbivorous fish C. striatus, a preeminent ciguateric fish of Polynesian waters.
      In order to study the possible role played by these bacteria in the toxicity of
      this fish, the quantitative and qualitative distributions of these isolates
      within toxic and non toxic fish are compared. The preliminary results are
      discussed.

PMID- 1364107
TI  - [The Second National Seminar on Moxibustion, November 2-6, 1992 Hefei city, Anhui
      Province, China].

PMID- 1364108
TI  - [Effect of moxibustion on the immune and anti-virus functions of the rat infected
      with epidemic hemorrhagic fever virus].

PMID- 1364106
TI  - Light and electron microscopic observation of experimental palytoxin poisoning in
      mice.
AB  - The effects of palytoxin on young male ICR mice were compared with the combined
      effects of palytoxin and ouabain or those of several cations as well as the
      effects of potassium. The target organs of palytoxin were the heart, kidney,
      pancreas, small intestine and liver. Pathomorphological changes of the heart
      induced by palytoxin were similar those of a lethal dose of KC1. However, the KC1
      treated animals did not show any changes in the kidney. Mice given ouabain at
      doses up to 5 mg/kg also showed similar injuries in proximal as well as distal
      convoluted urinary tubules, while the heart of mice given ouabain at the same
      doses showed no discernible morphological changes. Ouabain 5 mg/kg did not
      influence the severity of injuries both in the heart and kidney induced by
      palytoxin at 4 micrograms/kg. Therefore, it may be assumed that palytoxin
      poisoning is a symptom-complex of hyperkalemia and causes a profound inhibition
      of Na+, K(+)-ATPase.

PMID- 1364109
TI  - [Effect of moxibustion on humoral factors in the rat infected with epidemic
      hemorrhagic fever virus].

PMID- 1364110
TI  - Chronic in utero beta-blockade alters fetal lung development.
AB  - Pregnant rats received propranolol (5 or 10 mg/kg/day) from day 10 of gestation;
      controls were untreated. Lung wet:dry weight ratios were increased in treated
      fetuses delivered by hysterotomy at day 21; no difference was seen at birth after
      vaginal delivery. On subsequent days, treated pups exhibited higher wet:dry
      weight ratios, implying impaired postnatal lung water clearance. Surfactant pools
      were decreased proportionately at both doses. Ongoing surfactant synthesis was
      unaffected at either dose. Baseline secretion was reduced for those exposed to 10
      mg/kg/day. Secretory response to beta-agonist stimulation was impaired in both
      treatment groups. Chronic beta-blockade alters fetal lung water clearance,
      surfactant stores, and secretory response to beta-agonists.

PMID- 1364111
TI  - [Interactions of the macrocellular neurosecretory system of the hypothalamus and
      the endocrine pancreas of rats in adaptation to hypoxia].
AB  - Daily hypoxia (6 h, 6000 m) changed the functional state of endocrine pancrease
      of male and female Wistar rats. The actions of hypoxia on functional state of
      supraoptic (SO) and paraventricular (PV) nuclei of hypothalamus and islet cells
      of endocrine pancreas were examined using immunocytochemical, histochemical,
      morphometric and radioimmunoassay methods. Increase of insulin biosynthesis in
      beta cells and glucagon secretion of alpha cells, and decrease of the
      somatostatin contents in delta cells of pancrease islets have been investigated.
      The functional activity of vasopressinergic magnocellular subnucleus of PV
      increased, but that of SO decreased with reduction of vasopressin blood
      concentration at the same time. The functional state of oxytocin synthesis
      subdivisions of PV and SO were sex dependent, but the oxytocin contents in median
      eminence increased.

PMID- 1364112
TI  - [Thrombosis prophylaxis using plasmin and its combination with alpha
      adrenoreceptor antagonists].
AB  - Using two models of experimental thrombosis (arterio-venous shunt and Wessler's
      model) the effect of plasmin and its combination with alpha-adrenoreceptor
      antagonists on the formation of thrombus was studied on white rats. It was
      established that the efficacy of prophylactic of thrombosis by plasmin only was
      low: middle ball of thrombosis was 2.5-3.0. The combination of plasmin with alpha
      adrenoblockers dihydroergotoxine or prazosin under these conditions is most
      efficient against the formation of thrombus (middle ball of thrombus in this case
      was 0.8-1.1). Prazosin under certain conditions have some advantages.

PMID- 1364113
TI  - Two RNA-binding motifs in the double-stranded RNA-activated protein kinase, DAI.
AB  - The protein kinase DAI, the double-stranded RNA-activated inhibitor of
      translation, is an essential component of the interferon-induced cellular
      antiviral response. The enzyme is regulated by the binding of activator and
      inhibitor RNAs. We synthesized DAI in vitro and located its RNA-binding domain
      within the amino-terminal 171 residues. This domain contains two copies of an RNA
      binding motif characterized by a high density of basic amino acids, by the
      presence of conserved residues, and by a probable alpha-helical structure.
      Deletion of either of the two motifs prevents the binding of dsRNA, but their
      relative positions can be exchanged, suggesting that they cooperate to interact
      with dsRNA. Clustered point mutations within the RNA-binding motifs and
      duplications of the individual motifs indicate that the first copy of the motif
      plays the more important role. Mutations that impair binding have similar effects
      on the binding of double-stranded RNAs of various lengths and of adenovirus VA
      RNAI, implying that discrimination between activator and inhibitory RNAs takes
      place subsequent to RNA binding.

PMID- 1364115
TI  - Cytokines, Leukocytes and Vascular Diseases. Proceedings of the GEFAL
      International Workshop. St. Paul de Vence, France, April 11-12, 1992.

PMID- 1364114
TI  - Age related decline in the expression of proliferating cell nuclear antigen in
      human diploid fibroblasts.
AB  - Proliferating cell nuclear antigen mRNA and protein levels were determined in
      human diploid fibroblasts of different in vitro ages as they progressed through
      the cell cycle. Cells were analyzed at G0; at various stages of G1, including the
      G1/S interface; and during S. At all in vitro ages, PCNA message levels were low
      to undetectable at G0, were evident 8 to 12 h following entrance into G1, peaked
      at G1/S and declined during S phase. Message levels were 2-3-fold lower in older
      populations at all stages of the cell cycle tested. PCNA protein increased from
      G0 through S phase in both age groups with 2-3-fold less being found in older
      cells. The decline in PCNA mRNA in older populations was not the result of
      changes in mRNA turnover or transcription. The results suggest that the reduction
      in PCNA expression is due to an age related alteration in a post-transcriptional
      regulatory function. The decline in the expression of the PCNA gene would
      contribute to the inability of older cells to initiate replicative DNA synthesis.

PMID- 1364116
TI  - Cellular immune and cytokine pathways resulting in tissue factor expression and
      relevance to septic shock.
AB  - Cells of monocyte lineage serve as effector cells in the cellular immune
      response. In addition, they respond to LPS and cytokines with activation and
      expression of inflammatory effector gene products similar to those elicited by
      the antigen driven response. The response to antigen proceeds at the T helper
      cell level through two independent forms of cellular collaboration, contact and
      lymphokine. We review the control of expression of the Tissue Factor (TF) gene
      and the function of the TF protein. The enhanced initiation of transcription of
      the TF gene appears to require engagement of a 56 bp LPS Response Element, an
      enhancer that is engaged by both AP-1 type heterodimeric complexes as well as NF
      kappa B like heterodimeric complexes. Dissociation of NF kappa B from Ig kappa B
      by cytokine and LPS stimulation, and possibly activated T cells, may represent a
      common pathway to induction of the TF and other inflammatory genes. Enhancement
      of expression of TF is observed upon adhesion of Mo to endothelial cells and
      extracellular matrix proteins, as well as upon engagement of leukocyte integrins.
      The biological effects that follow from expression of TF by vascular cells have
      been resolved by analysis of function aided by the use of recombinant full length
      TF and truncated surface domain of TF. The rules of assembly of the cognate
      ligands of TF, namely the zymogen plasma factors VII and the serine protease
      factor VIIa, with the soluble surface domain of TF in free solution, in the
      presence of phospholipid surfaces and cell surface and of the anchored TF
      molecule have been described. It is evident that assembly of the surface domain
      of TF with VIIa to form the binary TF.VIIa complex induces a significant increase
      in the Kcat of the catalytic domain of VIIa for small peptidyl substrates and
      more profoundly for protein substrate. This provides substantial evidence for an
      allosteric effect on the catalytic cleft of VIIa that is imparted by binding to
      TF, its cognate catalytic cofactor. It is also evident that the TF.VIIa complex
      is proteolytically active and can activate the zymogen plasma factor X to the
      serine protease Xa in free solution, inferring that extended substrate
      recognition by induced structural loci of the TF.VIIa complex are created from
      either or both proteins to constitute a new recognition structure. It is also
      evident that association of X with charged phospholipid surfaces enhances the
      proteolytic activation of this zymogen by increasing recognition and
      susceptibility of the sessile peptide bond deduced from the markedly decreased Km
      and increased Kcat.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1364118
TI  - Ethics and the Epidemiology of Malaria. Proceedings of a seminar. Sao Paulo,
      Brazil, October 8-10, 1991.

PMID- 1364119
TI  - Malaria parasites, vectors and biologic cycle.

PMID- 1364117
TI  - [Effect of dietary polyunsaturated fatty acids on the content and metabolism of
      glutathione in rat kidney].
AB  - The effect of dietary polyunsaturated fatty acids (PIFA) upon the content of
      reduced glutathione (GSH) of the kidney was studied in 32 male Wistar rats. Two
      equal size groups were fed diets supplemented with either 10% or 18% corn oil.
      Sixteen hours before death, half of each experimental group was submitted to
      fasting. The content of GSH and the activity of gamma glutamyl transpeptidase
      (GGTP) and gamma glutamyl cysteine synthetase was determined in kidney tissue.
      Fasting led to a reduction of GSH from 3.21 +/- 0.54 to 1.25 +/- 0.20 mumol per
      gm in the group fed 10%. PIFA. Equivalent figures for the group fed 18% PIFA were
      3.49 +/- 0.54 and 0.49 +/- 0.08, respectively. GGTP activity increased
      significantly after fasting but no differences were observed according to level
      of PIFA intake. The exaggerated reduction of GSH during fasting after a high PIFA
      intake may expose the animals to risk of cell damage induced by peroxides or
      other oxidating agents.

PMID- 1364120
TI  - [Familial acromegaly. Apropos of a case. Review of the literature].
AB  - Two brothers and a sister with acromegaly--one of them with acromegalogigantism-
      are described. They all presented pituitary adenomas, and the diagnosis was made
      between the ages of 17 and 29. There was no feature of multiple endocrine
      neoplasia. The familial investigation consisted of detailed interrogation, basal
      hormonal evaluation and HLA determination (haplotypes A and B) in 14 members,
      including the patients themselves. Despite basal plasma GH levels ranging from
      8.00 to 10.00 ng/ml in 3 other family members, the normality of both GH response
      to induced-hyperglycemia and CT-imaging of the pituitary gland excluded the
      diagnosis of acromegaly in these subjects. No correlation with the HLA haplotypes
      was observed. Differential diagnosis with familial multiple endocrine neoplasia
      (MEN type 1) is discussed. Previous reports of familial acromegaly are reviewed
      and analysed. It appears that familial acromegaly may be considered as a specific
      entity for two main reasons: 1) owing to the low incidence of acromegaly in the
      general population, familial cases are unlikely to be fortuitous. 2) most of the
      reported cases share some common clinical features, such as a male predominance,
      a high incidence of acromegalogigantism, and the presence of a pituitary
      macroadenoma. However, the primitive disorder and the genetic transmission of the
      disease are still unknown.

PMID- 1364122
TI  - [A new neuroleptic: zuclopenthixol (Clopixol)].

PMID- 1364121
TI  - [Erythrocyte membrane transport of amino acid precursors of monoamines in
      schizophrenic patients. Comparison with depressive patients].
AB  - The study concerned 72 schizophrenic and 200 depressed patients hospitalised
      between 1983 and 1990. The erythrocyte membrane transports (EMT) of L-tyrosine
      and L-tryptophan (at 37 degrees, 0 degrees and 37-0 degrees) of schizophrenics
      without treatment nor depression were different compared to controls and
      depressed patients. The schizophrenics under neuroleptic treatment and/or
      depressed showed same means of EMT values as depressed patients. The slopes of
      the correlations between EMT of tyrosine or tryptophan at 37 degrees, 0 degrees
      and 37-0 degrees, as well as that between plasma levels of these amino acids,
      were parallel. However the slopes of the correlations between EMT of tyrosine and
      tryptophan were different according to the subgroups of patients: the
      perturbations of EMT were related to the clinical characteristics. In depressed
      patients and in schizophrenic patients under neuroleptic treatment and/or
      depressed, little changes in EMT of tyrosine were related to high changes of EMT
      of tryptophan.

PMID- 1364124
TI  - Neural, hormonal, and paracrine regulation of gastrin and acid secretion.
AB  - Physiological stimuli from inside and outside the stomach coverage on gastric
      effector neurons that are the primary regulators of acid secretion. The effector
      neurons comprise cholinergic neurons and two types of non-cholinergic neurons:
      bombesin/GRP and VIP neurons. The neurons act directly on target cells or
      indirectly by regulating release of the hormone, gastrin, the stimulatory
      paracrine amine, histamine, and the inhibitory paracrine peptide, somatostatin.
      In the antrum, cholinergic and bombesin/GRP neurons activated by intraluminal
      proteins stimulate gastrin secretion directly and, in the case of cholinergic
      neurons, indirectly by eliminating the inhibitory influence of somatostatin
      (disinhibition). In turn, gastrin acts on adjacent somatostatin cells to restore
      the secretion of somatostatin. The dual paracrine circuit activated by antral
      neurons determines the magnitude of gastrin secretion. Low-level distention of
      the antrum activates, preferentially, VIP neurons that stimulate somatostatin
      secretion and thus inhibit gastrin secretion. Higher levels of distention
      activate predominantly cholinergic neurons that suppress antral somatostatin
      secretion and thus stimulate gastrin secretion. In the fundus, cholinergic
      neurons activated by distention or proteins stimulate acid secretion directly and
      indirectly by eliminating the inhibitory influence of somatostatin. The same
      stimuli activate bombesin/GRP and VIP neurons that stimulate somatostatin
      secretion and thus attenuate acid secretion. In addition, gastrin and fundic
      somatostatin influence acid secretion directly and indirectly by regulating
      histamine release. Acid in the lumen stimulates somatostatin secretion, which
      attenuates acid secretion in the fundus and gastrin secretion in the antrum.

PMID- 1364123
TI  - Gene expression during cardiac development.
AB  - The vertebrate heart forms as two concentric epithelial cylinders of myocardium
      and endocardium separated by an extended basement membrane matrix commonly
      referred to as cardiac jelly. Subsequent maturation involves a complex series of
      events including asymmetric changes in cell shape and division which contribute
      to bending and the formation of the bulboventricular loop, the formation of
      specialised tissues including endocardial cushion tissue of the atrioventricular
      (AV) and outflow tract regions, the development of conductive tissue and myocyte
      maturation leading to the overall pattern of expression characteristic of mature
      heart muscle. These processes depend on a precise spatial and temporal control of
      gene expression both of genes encoding regulatory molecules and those encoding
      structural components of the heart. In this chapter we address three aspects of
      cardiac development, namely, the determination of cell fate during formation of
      endocardial cushion tissue in the embryonic heart, transitions in troponin gene
      expression during fetal myocyte maturation, and the use of cloning techniques
      based on the polymerase chain reaction for identifying transcription factors
      present in the heart.

PMID- 1364126
TI  - [Visual and motor functions in schizophrenic patients].
AB  - In the present work, visual and motor functions have been explored in 26 chronic
      schizophrenic patients, and 7 acute schizophrenic patients, compared with 26
      normal controls, by means of the Bender-Gestalt Test. Parameters under
      consideration were: Form distortion, rotation, integration, perseveration, use of
      space, subtle motricity, score (global parameter), and time employed. As regards
      distortion and rotation there have been highly significant differences between
      chronic patients and control group. Among acute patients, it was observed that
      perseveration was also highly significant. Conversely, integration and use of
      space did not differ significantly among the three groups involved. The global
      score, resulting from all the above mentioned parameters showed important
      differences between both patient groups on the one hand, and control group on the
      other hand. Taking into account that patients were being administered neuroleptic
      drugs, it can safely be said, however, that the Bender-Gestalt Test allows to
      recognize alteration in perceptual closure consistent with a loss of the
      objective structure of perceived phenomena, in both chronic and acute patients.

PMID- 1364125
TI  - The H2-receptor antagonist era in duodenal ulcer disease.
AB  - This paper reviews the remarkable impact of H2-receptor antagonists on duodenal
      ulcer management. The development and the scientific rationale of these agents
      are presented, and efficacy and safety aspects in the short- and long-term
      treatment of duodenal ulcer disease discussed. Attention is focused on the
      possible role of "acid rebound" in ulcer relapse following the withdrawal of
      therapy and on the clinical relevance of prolonged suppression of acid secretion
      in patients on long-term therapy.

PMID- 1364127
TI  - Genetic aspects of multidrug resistance.
AB  - Gene amplification is responsible both for dihydrofolate reductase induced
      methotrexate resistance, and for the P-glycoprotein encoding multigene family
      induced multidrug resistance. The 6 pairs of hydrophobic regions of the P
      glycoprotein fold up in a snake-like structure through the lipidic layers of the
      cell membrane. Other detoxification mechanisms include the glutathione S
      transferase 'pi', but without gene amplification.

PMID- 1364130
TI  - Effects of heat treatment on mechanical properties of base metal wrought wire
      clasps.
AB  - The purpose of this study is to determine the effects of heat treatment and
      soldering on the change of shape and mechanical properties of cobalt-chromium
      nickel alloy wrought wire clasps. The change of distance between the tips of the
      clasp arm was measured and mechanical properties were examined using the bending
      test. The following results were obtained. 1) By heat treatment at 500-700
      degrees C for 10 minutes, bending rigidity and deflection at the proportional
      limit of the clasp arm increased significantly (p < 0.01), while permanent
      deformation after the bending test decreased considerably (p < 0.01). Concerning
      the deformation of clasp arms by heating, the distance between clasp tips
      increased remarkably above 500 degrees C (p < 0.01). 2) These mechanical
      properties of clasp arms were improved both by electric resistance soldering with
      silver solder and by heat treatment at 500 degrees C for 10 minutes after
      soldering. From these results, it was concluded that electric resistance
      soldering and adequate heat treatment were very effective to improve the
      mechanical properties of the clasp arm, especially to increase the deflection at
      the proportional limit and reduce the permanent deformation.

PMID- 1364128
TI  - The multiple drug resistance gene, MDR1: expression at the protein and RNA
      levels.
AB  - A comparison of three different approaches to detect MDR1 expression in myeloid
      leukemia cells was undertaken. With respect to the 4 different antibodies
      studied, a high proportion of false positive reactions were detected. Substantial
      discordance between MDR1 expression as indicated by Northern blot analysis, PCR,
      and immunohistochemistry was found. These findings complicate the clinical
      interpretation of data derived from these methods.

PMID- 1364129
TI  - Short communication: possible activity of beta-carotene in patients with the AIDS
      related complex. A pilot study.
AB  - In a pilot single blind study, beta-carotene (BC) supplementation produced, in
      ARC patients under current treatment, apparent recovery from asthenia, fever,
      nocturnal sweating, diarrhoea, loss in weight, and led as a result to an
      improvement in general health and working efficiency, but not to an improvement
      in multiple district lympho-adenopathies. Nevertheless, BC appeared to prevent
      progress to AIDS and, in addition, to lower the effective dosage of AZT used in
      one case of ARC developed into AIDS, producing a recovery from opportunistic
      infections and an inhibition of Kaposi sarcoma diffusion, in line with a two-fold
      rise in CD4 counts.

PMID- 1364131
TI  - Influence of dimensional factors and heat treatment on permanent deformation of
      wrought wire clasps.
AB  - The purpose of this study is to examine the fatigue profiles of wrought wire
      clasps during the clinical use. Cobalt-chromium-nickel alloy wires were bent into
      circular beams, which dimensions and fabrication methods were similar to the
      clinical cases. Deflections of 0.5 mm in a normal direction were applied 10,000
      times to the tips of clasp arm and permanent deformations were measured. The
      following results were obtained. 1) The clasp arms with larger cross sectional
      diameter, shorter length and smaller radius of curvature showed larger amounts of
      permanent deformation. 2) The amounts of permanent deformation of the clasp arm
      remarkably decreased by electric resistance soldering and decreased further more
      by heat treatment at 500 degrees C for 10 minutes after soldering regardless of
      the number of deflection. From the results of this study, it was concluded that
      dimensional factors and heat treatment influenced the permanent deformation of
      the wrought wire clasps remarkably. Therefore, considering these factors, wrought
      wire clasps could be designed to reduce permanent deformation.

PMID- 1364133
TI  - [9th Brazilian Congress on Cardiac Arrhythmias. S. Jose do Rio Preto, 10-12
      December 1992. Abstracts].

PMID- 1364132
TI  - P-glycoprotein expression in refractory hematological neoplasms and circumvention
      of resistance with verapamil or cyclosporine A containing protocols.
AB  - Either p-glycoprotein (pgp) or the encoding gene mdr1 expression has been
      reported to be correlated with multidrug resistance and poor treatment response.
      To investigate the incidence of pgp in refractory hematological neoplasms we
      analyzed malignant cells from 40 patients by an immunoperoxidase method using the
      monoclonal antibody C219. Pgp was positive in 75% of acute nonlymphoblastic
      leukemia (ANLL) and 50% of acute lymphoblastic leukemia (ALL). Pgp positivity was
      similarly distributed in both Tdt (-) and (+) ANLLs (64% versus 100%). Addition
      of Verapamil (VRP) (12 patients) or Cyclosporine A (CsA) (7 patients) to the
      previous chemotherapy protocol resulted in complete response in 7 (58%) and 3
      (43%) of the patients respectively. Partial response was observed in one patient
      who received CsA. Both chemosensitizers were tolerated well with few reversible
      side effects. The preliminary results of this study have been presented in the
      15th International Cancer Congress, August 1990 Hamburg, Germany.

PMID- 1364134
TI  - Memory consolidation of a habituation task: role of N-methyl-D-aspartate,
      cholinergic muscarinic and GABA-A receptors in different brain regions.
AB  - 1. The immediate post-training microinjection of the N-methyl-D-aspartate
      receptor antagonist amino-5-phosphonopentanoic acid (5 micrograms) or of
      scopolamine, the cholinergic muscarinic antagonist (2 micrograms), into the
      dorsal hippocampus of rats caused retrograde amnesia for habituation to a novel
      environment, as measured by the number of rearings and crossings performed in a
      test session. In contrast, picrotoxin (0.08 microgram), the indirect GABA-A
      antagonist, caused retrograde memory facilitation. 2. Receptor agonists
      administered into the hippocampus had effects opposite to those of the respective
      antagonists: glutamate (5 micrograms) and oxotremorine (2 micrograms) enhanced
      memory and muscimol (0.03 microgram) was amnestic. 3. Aminophosphonopentanoic
      acid, scopolamine and picrotoxin had no effect when injected into the amygdala or
      medial septum. Our result contrasted with the recent report of an inhibitory
      avoidance task in which these drugs, at the doses used here, were effective when
      injected post-training into any of the three structures. 4. These findings
      suggest that similar neurotransmitter mechanisms operate in different brain
      regions in order to regulate memory consolidation processes; however, there is a
      specialization of these brain regions in relation to different types or
      components of memory.

PMID- 1364135
TI  - Electrophysiological effects of somatostatin at the supraventricular level of
      isolated guinea pig hearts.
AB  - 1. The objective of the present study was to evaluate the electrophysiological
      effects of the peptide somatostatin (SST) at the supraventricular level in
      isolated guinea pig hearts. 2. ECG recording from isolated hearts perfused by the
      Langendorff method indicated that 1.0 microM SST induced a decrease in heart rate
      from 174 +/- 15 to 157 +/- 9 bpm (N = 6, P < 0.05), blocked AV conduction (the PR
      interval increased from 92 +/- 11 ms to 106 +/- 5 ms, N = 5, P < 0.05) and
      increased the QTc interval from 210 +/- 0 to 232 +/- 4 ms (N = 5, P < 0.05). The
      supraventricular effects of SST, particularly upon the AV conduction, were
      potentiated by a reduction in calcium concentration from 2.5 to 0.5 mM in the
      perfusing solution. Thus, 1.0 microM SST induced 2nd degree AV conduction block
      progressing to AV dissociation in 75% of the hearts in the low calcium medium
      instead of the first degree conduction block observed in all hearts in normal
      calcium medium. 3. His bundle electrogram evidenced a complete A-H dissociation
      without significant change in the H-V interval and microelectrode studies showed
      a complete abolition of the AV node action potential in the presence of 1.0
      microM SST. Both results demonstrate that the site of AV conduction block induced
      by SST is at the AV node. 4. All the supraventricular effects of SST were
      transitory, subsiding within about 10 min of hormone exposition, showing
      desensitization. 5. The effects of somatostatin here described were not blocked
      by 10 microM atropine, indicating that they are not mediated by muscarinic
      receptors. 6. These data provide a direct electrophysiological demonstration of
      the supraventricular effects of SST, and suggest that this peptide decreases
      calcium influx during the action potential.

PMID- 1364136
TI  - The X-linked dystonia-parkinsonism syndrome (XDP): clinical and molecular genetic
      analysis.
AB  - Dystonia and parkinsonism are two major representatives of movement disorders.
      The X-linked dystonia-parkinsonism syndrome (XDP) serves as a model system for
      the study of both dystonia and parkinsonism since both symptom complexes occur
      together and are inherited as Mendelian traits with very high penetrance. XDP,
      which is endemic to the Philippine island of Panay, originated by a single
      mutation ("genetic founder effect"), thus assuring homogeneity of the disorder at
      the molecular level. The disease locus, DYT3, has been assigned to the proximal
      long arm (Xq12-21.1) of the human X chromosome. A strategy is described to
      isolate this gene by positional cloning. The rationale of this strategy, the
      major methods involved and technical terms are explained.

PMID- 1364137
TI  - DNA fingerprints of Pseudomonas spp. using rotating field electrophoresis.
AB  - Rotating field electrophoresis (RFE) was applied to evaluate the usefulness of
      this technique for identification of several Pseudomonas strains with suspected
      importance in deliberate releases. Genomes of common wild-type or genetically
      modified strains of Pseudomonas fluorescens, Pseudomonas stutzeri, Pseudomonas
      putida and Pseudomonas aeruginosa were digested with rare-cutting restriction
      endonucleases and subjected to pulsed field gel electrophoresis. Restrictions
      with SpeI or XbaI produced 11-28 large DNA fragments in the range of 50-500 kb
      pairs. The specific genomic fingerprints were different for most strains of the
      same species, but identical for closely related strains. Differences were not
      affected by the presence of natural or genetically modified plasmids.

PMID- 1364138
TI  - Regularly scheduled versus as-needed use of inhaled beta agonists in the
      treatment of asthma.

PMID- 1364140
TI  - Behavioral effects of gut hormones in neonatal rats: I. Somatostatin
      administration during the first postnatal week.
AB  - This exploratory study attempted to uncover behavioral and physical outcomes of
      changes in the peripheral SMS system in the first postnatal week. On postnatal
      days 1-7, Sprague-Dawley rat pups received daily s.c. injections of Somatostatin
      (SMS; 8 or 40 micrograms/kg), saline, or CPP-1 (8 or 40 micrograms/kg), a
      putative SMS receptor antagonist. Physical growth and neurobehavioral development
      of the pups, assessed on days 3, 6, 9 and 12, were not affected, in 3 separate
      replications (n = 11/treatment/replication). In contrast, neonatal CPP-1 (40
      micrograms/kg) reduced separation distress on day 14, as measured by ultrasonic
      vocalization and activity. In addition, neonatal SMS (40 micrograms/kg) tended to
      impair learning on a milk-rewarded Y-maze on days 15-16. These findings support
      further examination of the potential role of SMS in behavioral development.

PMID- 1364142
TI  - Proceedings of the 1991 XIIth World Congress on Sarcoidosis. Kyoto, Japan,
      September 8-13, 1991.

PMID- 1364139
TI  - Neuroendocrine regulation of immunity: the effects of noradrenaline in Xenopus
      laevis, the South African clawed toad.
AB  - A functional association between the peripheral nervous and the immune system in
      Xenopus laevis, the South African clawed toad, is demonstrated. This association
      involves the neurotransmitter noradrenaline (NA), produced and released by the
      sympathetic nerves of the spleen. Chemical sympathectomy prior to immunization
      reduces splenic NA, and decreases thymus-dependent (TD), but increases thymus
      independent (TI), antibody responses. Immune challenge with representatives of
      the three antigen classes affects splenic NA levels differentially. Thus, the
      modulatory effect of NA on immunity will depend on the immunogen used. Carrier
      priming of helper function in TD responses stimulates a transitory NA release in
      the spleen, while subsequent immunization activates a more prolonged release. The
      two types of challenge differ in the antigenic dose given. The effects of NA also
      depend on the time when it is applied. If used early in the in vivo TD response,
      antibody production is increased, but if given later, suppressor function is
      stimulated, thus decreasing antibody production. NA increases both amplifying and
      suppressing T cell functions in TD responses through stimulation of the alpha 2
      adrenoceptor. Alpha 2 adrenoceptor stimulation decreases, and beta adrenoceptor
      stimulation increases, anti-TNP reactivity. Since an alpha 2 receptor agonist
      does not affect lectin-stimulated T cell mitogenesis, while a beta receptor
      agonist depresses it, NA appears to up-regulate T cell functions by affecting
      their maturation, rather than their clonal expansion.

PMID- 1364141
TI  - The role of melatonin in the antipsychotic and motor-side effects of
      neuroleptics: a hypothesis.
AB  - Three phenomena concerning the antipsychotic action of classic neuroleptic drugs
      have not been adequately explained by the dopamine hypothesis: (1) administration
      of neuroleptic drugs is commonly associated with an initial period of 3-6 weeks
      prior to demonstration of antipsychotic effects; (2) similarly, neuroleptic
      induced Parkinsonism commonly emerges only after several weeks of neuroleptic
      therapy; (3) moreover, Parkinsonism may disappear despite continuous neuroleptic
      treatment. An understanding of these phenomena might shed new light into the
      nature of the antipsychotic actions of these agents, and hence the
      pathophysiology of schizophrenia. We propose that the increase in melatonin
      secretion, which occurs with the initiation of neuroleptic therapy, may be
      responsible for the delay in the antipsychotic effects of neuroleptics and may
      also account for the lag in the development of drug-induced Parkinsonism as well
      as its disappearance. The implications of this hypothesis for the treatment of
      schizophrenia and the prophylaxis of drug-induced Parkinsonism are discussed.

PMID- 1364143
TI  - ISBT Brazil '92. XXII Congress of the International Society of Blood Transfusion.
      XX Brazilian Congress of Hematology. Extraordinary Congress of the Brazilian
      College of Hematology. Sao Paulo, Brazil. October 8-13, 1992. Abstracts.

PMID- 1364144
TI  - Monozygotic twins with discordant sex.
AB  - A nine-year-old girl with short stature was referred to the department of
      pediatrics at Kyushu University. The clinical diagnosis was Turner syndrome;
      karyotypic analysis performed on peripheral blood, using GTG techniques,
      demonstrated a 45,X/47,XYY (17:83) mosaicism. Her twin brother, a phenotypically
      normal male, had the same karyotype; 45,X/47,XYY (3:97) on peripheral blood.
      Their skin fibroblast karyotypes showed the same mosaicism, ie. 45,X/47,XYY
      (41:59 and 31:69 respectively). On eleven biochemical genetic markers the twin
      pair were concordant, thus the likelihood of monozygosity was 0.99527034. In
      addition, the analysis of variable number of tandem repeat (VNTR) markers
      revealed the likelihood of monozygosity to be 0.99944386. The most plausible
      explanation of the X/XYY mosaicism was nondisjunction of the Y in the first
      cleavage division of the 46,XY zygote. A disproportionate rate of cell
      populations with 45,X and 47,XYY in the twinning process of the X/XYY embryo,
      especially in the germ lines, would result in discordant sex in twin pairs.

PMID- 1364145
TI  - Evidence for two independent mechanisms of GABA release induced by veratridine
      and glutamate in monolayer cultures of chick embryo retinal cells.
AB  - GABA is a major inhibitory neurotransmitter in the central nervous system,
      including the retina. In the present paper we present evidence for the existence
      of two independent mechanisms for GABA release in cultured retina cells. Eight
      day-old chick embryo retinas were dissociated and plated in 35-mm plastic dishes
      and cultured for 3 or 7 days at 37 degrees C. An increase of 3 to 5-fold in GABA
      release was observed in cultures of 3 or 7 days in vitro preloaded with 0.5
      microCi [3H]GABA and stimulated with glutamate (100 microM) or veratridine (100
      microM). Tetrodotoxin (1 microM) blocked the release induced by veratridine but
      not by glutamate. In contrast, the non-N-methyl-D-aspartate (NMDA) glutamate
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 100 microM) was able to
      inhibit GABA release promoted by glutamate but not by veratridine. These results
      indicate that depolarization of retinal cells by opening of voltage-dependent
      sodium channels or activation of non-NMDA glutamate receptors can trigger
      intracellular events that lead to calcium-independent GABA release.

PMID- 1364146
TI  - Brain serotoninergic stimulation reduces the water intake induced by systemic and
      central beta-adrenergic administration.
AB  - 1. This study was undertaken to determine if the stimulation of central
      serotoninergic receptors affects the thirst-inducing action of systemically or
      intracerebroventricularly (icv) injected isoproterenol. 2. Male Wistar rats
      weighing 220-300 g were used in groups of 10-14 animals each. Normally hydrated
      rats implanted with a delay cannula into the third ventricle were injected icv
      with the 5HT1C/5HT2 agonist MK212 (50 nmol/2 microliters) prior to administration
      of isoproterenol sc (330 micrograms/kg body weight) or icv (10 and 25 and 50
      micrograms/2 microliters). 3. Icv injections of MK212 reduced the water intake
      induced by isoproterenol injected systemically (56%) and by the two lowest doses
      of isoproterenol injected icv (76 and 86%, respectively). 4. The results suggest
      that the central serotoninergic system modulates the central beta-adrenergic
      system involved in water intake. 5. Taken together with previous results showing
      that the activation of 5HT1C/5HT2 receptors promotes a reduction of the
      dipsogenic response evoked by water deprivation or by icv injection of
      angiotensin II or carbachol, the present data suggest that the central
      serotoninergic system plays a ubiquitous role in the modulation of water intake
      behavior.

PMID- 1364147
TI  - General mechanisms of the effect of weightlessness on the human body.

PMID- 1364149
TI  - Proceedings of the National Heart, Lung, and Blood Institute Workshop on
      Hemostasis, Thrombosis, and Cardiovascular Disease. Bethesda, Maryland, October
      16-17. 1990.

PMID- 1364148
TI  - Proceedings of the National Heart, Lung and Blood Institute of the National
      Institutes of Health. Cholesterol and Heart Disease in Older People and in Women.

PMID- 1364150
TI  - Identification of mechanisms that may modulate the role of lipoprotein(a) in
      thrombosis and atherogenesis.
AB  - In this report, we review recent findings concerning the identification of
      mechanisms that may modulate the role of lipoprotein(a), or Lp(a), in thrombosis
      and atherogenesis. Lp(a) binds to surface-immobilized plasmin-modified fibrin,
      thus providing a mechanism for incorporating Lp(a) into the vessel wall. We found
      that homocysteine and other sulfhydryl-containing amino acids markedly increase
      the binding of Lp(a) to plasmin-modified fibrin. Our results suggest that
      homocysteine alters the structure of Lp(a) to expose lysine-binding sites on the
      apolipoprotein(a) portion of the molecule, and thus provide a potential
      biochemical link between thrombosis and atherogenesis. We also found that
      transglutaminases catalyze the incorporation of primary amines into Lp(a).
      Studies in cell culture systems have found that Lp(a) stimulates endothelial
      cells to synthesize and release plasminogen activator inhibitor-1. Further, Lp(a)
      inhibits the activation of transforming growth factor-beta in a coculture of
      bovine endothelial and smooth muscle cells.

PMID- 1364151
TI  - [Fragile X syndrome: current knowledge].
AB  - Fragile X syndromes is a disease characterized by the association of mental
      retardation and dysmorphic features to a fragile site on Xq27-3. It is a frequent
      genetic disorder (1 in 1,500 males) recognized only 20 years ago but remaining
      difficult to understand, because its transmission among generations does not
      correspond to the classical model of recessivity linked to chromosome X. In fact,
      carrier females can express the disease and transmitting males can be normal.
      With DNA probes, molecular biology has contributed to genetic counselling and
      prenatal diagnosis. Restriction polymorphisms have long been used to study the
      inheritance of fragile X syndrome and DNA markers' analysis improved risk
      estimates for carriers. From a clinical viewpoint, there was a need for more
      closely linked probes to help in prenatal diagnosis and to assess carrier status
      and hence reduce risk of recombination. In 1991, new probes allowed direct
      diagnosis of the Fra (X) mutation and a gene was sequenced. Nevertheless the
      understanding of the mechanism involved in the underlying mutation is still
      unknown. Geneticists, cytogeneticists and biologists must collaborate further to
      elucidate the fragile site mystery.

PMID- 1364152
TI  - [Hereditary porphyria and acquired porphyria in the child. Five case reports].
AB  - Two cases of inherited porphyrinopathies and three cases of acquired
      porphyrinopathies are described. The two inherited cases were cutaneous
      porphyrias with 50% reduction of enzyme activities: one case of erythropoietic
      protoporphyria in a 2 year-old male and one case of familial cutaneous porphyria
      in a 7 year-old boy. The three cases of acquired porphyrinopathy included one
      case of lead poisoning in a 3 year-old boy and 2 cases of hereditary tyrosinemia
      in 1 and 2 year-old infants. Urinary and erythrocytes porphyrins and precursors
      (5 aminolevulinic acid and porphobilinogen) levels were used for diagnosis and to
      follow the response to treatment.

PMID- 1364155
TI  - [Relevant pharmacologic data as a guide for use of beta-blockers in psychiatry].
AB  - In addition to their competitive blockade of the beta-receptors, beta-adrenergic
      blocking drugs possess ancillary properties that may modulate their clinical
      effects. Among these properties, beta 1-selectivity, intrinsic sympathomimetic
      activity, lipid solubility, may affect pharmacokinetic and pharmacodynamic
      properties of beta-blockers. It could appear that lipid soluble drugs gain access
      to the Central Nervous System (CNS) more easily. But CNS effects of beta-blockers
      are probably modulated by other parameters. With those pharmacological data, the
      authors propose briefly a schematic use of main beta-blockers in psychiatry.

PMID- 1364153
TI  - [HIV infection in the child after materno-fetal transmission: early treatment
      with azidothymidine and prevention of secondary infectious complications].
AB  - Twenty-four perinatally HIV infected children received early treatment as soon as
      the diagnosis of viral contamination was established. In 13 cases (group 1), this
      diagnosis was based on a viremia and/or antigenemia during the first 6 months of
      life. In 11 cases (group 2), children were more than 15 months-old and had a
      positive HIV antibody test. Therapy included azidothymidine (AZT, 400 mg/m2/d)
      and the prevention of secondary infectious complications with intravenous
      immunoglobulin and cotrimoxazole. With a median follow-up of 26 months, we
      reported no case of severe secondary infection and no case of encephalopathy.
      Hematological side effects of AZT were rarely observed. Only one patient
      developed anemia. In all other cases, the only hematological abnormality was
      macrocytosis of red blood cells. Before treatment, the mean value of T4 cells age
      adjusted count was 96, 86 and 91%, respectively, for groups 1, 2 and the entire
      study group. At the time of analysis, these values were 64, 62 and 63%
      respectively. This decrease was statistically significant for group 1 and for the
      entire study group, but did not reach statistical significance for group 2. These
      data show that AZT is probably insufficient as a long-term therapy for HIV
      infected children. Other therapeutic approaches need to be developed in the
      future, notably the combination of anti-retroviral drugs.

PMID- 1364156
TI  - [Dysthymia. Proceedings of a meeting. Marseille, France, 31 January-1 February
      1992].

PMID- 1364154
TI  - [Platelet serotonin in infantile autism. Cross-over effects of a dopamine agonist
      and an antagonist].
AB  - In infantile autism, the serotoninergic (5-HT) hypothesis is corroborated by
      biological dosages and therapeutic effects of fenfluramine which decrease blood
      serotonin. However other drugs, such as dopaminergic agonists or antagonists,
      have therapeutic effects. Therefore, we tested the hypothesis that two
      dopaminergic (DA) drugs have a similar 5-HT effect underlying the therapeutic
      efficiency. We evaluated in a randomized, double-blind and cross-over study, the
      effects of a DA agonist (bromocriptine) and a DA antagonist (amisulpride) on
      platelet 5-HT in infantile autism. The prolactinemia, reflecting the DA action,
      has been also measured. Nine children, aged from 4 to 13 years, according to the
      DSM III for infantile autism, received either drug in a random order during four
      weeks with an in-between placebo period of six weeks. The dosages of platelet 5
      HT and serum prolactin were carried out at the beginning and at the end of every
      phase of treatment (active or placebo) with radioenzymology and radioimmunoassay
      methods respectively. The principal results on serum prolactin show neither order
      x treatment interaction, nor order effect but a significant treatment effect (p <
      0.01): amisulpride increases serum prolactin whereas bromocriptine decreases
      according to the usual data. About platelet 5-HT, there is neither order x
      treatment interaction, nor treatment effect but a significant order effect (p <
      0.01). Both drugs increase platelet 5-HT in the first phase of treatment. This
      order effect could be explained by a remanent effect of amisulpride after 6 wash
      out weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364157
TI  - [Dysthymic disorders and dopaminergic drugs].

PMID- 1364158
TI  - Graves' disease: evolution and prognosis after eight months of treatment with
      methimazole.
AB  - We studied 26 patients with Graves' disease, from a population with sufficient
      iodine supply, treated with high doses of methyl mercaptoimidazole (MMI) during
      eight moths. We evaluated: a) their evolution after treatment withdrawal; b) the
      correlation between evolution and TSH-receptor antibodies (TRAb), thyroid hormone
      levels, microsomal antibodies (MAb), T3/T4 index and clinical data; c) their
      prognosis. The patients were followed during 12-60 months, and blood samples were
      collected before treatment withdrawal. Out of 26 patients, 20 relapsed, with
      T3/T4 index and TRAb significantly higher than those under remission. The T3/T4
      index correlated with TRAb. All the TRAb-positive patients, and only 57.1% of the
      negatives, relapsed. The relapses were significantly more frequent prior to the
      6th month in the TRAb-positive patients than afterwards. The TRAb-negatives who
      relapsed during that period, showed TRAb and age means significantly higher than
      those under remission. The TRAb test, as a prognostic marker of evolution, showed
      a sensitivity of 60% and a specificity of 100%. No significant differences were
      found between evolution to relapse or to remission and the other parameters. It
      can be concluded that TRAb and T3/T4 index were different in the group that
      relapsed from that which remitted, and that a TRAb positive value, at the moment
      of treatment withdrawal, is a useful marker of relapse.

PMID- 1364159
TI  - [AIDS and tuberculosis: the immunopathogenic processes].
AB  - HIV infection is characterized by CD4+ lymphocyte depletion manifested through
      the loss of the immune response capacity. The resulting immunodeficit is
      expressed by the blocking of immune surveillance mechanisms and, thus, by the
      establishment of favourable conditions to the development of opportunistic
      infections and/or malignant processes. In tuberculosis, the immunodeficiency
      associated with HIV infection makes possible the evolution of a latent infection
      to a clinically manifest disease. Latent tuberculosis is characterized by the
      intracellular persistence of some metabolically inactive Tb bacillus forms which
      are incapable of multiplication. The conversion of these inactive into
      metabolically active forms capable of multiplication is usually neutralized by
      immunosurveillance mechanisms. The blocking of such mechanisms in case of CD4+
      cell depletion will allow the multiplication of metabolically active Tb bacillus
      forms, and the development of a clinically manifest tuberculosis. CD4+ lymphocyte
      depletion is the result of facilitating antibodies and certain cytokines, and of
      some autoimmune processes which also affect the non-infected CD4+ cells.
      Therefore, it is necessary that Tb chemoprophylaxis in HIV infected subjects
      should also be addressed to the processes initiating the immune deficit, which
      include autoimmune mechanisms as well as those facilitating HIV infection.

PMID- 1364160
TI  - [The 14th National Conference of Pneumophthisiology. Round table: the
      chemotherapy of bronchopulmonary suppurations].

PMID- 1364163
TI  - [An update on bronchoalveolar lavage (BALF)].

PMID- 1364161
TI  - [An update on tuberculosis].

PMID- 1364164
TI  - Antihistamine activity of Bryophyllum calycinum.
AB  - 1. The juice obtained by pressing the leaves of Bryophyllum calycinum
      (Crassulaceae) exhibited histamine-blocking activity. 2. The juice contains
      flavonoid compounds, carbohydrates and mineral salts. A flavonoid fraction
      (fraction B) obtained by partitioning the juice between n-butanol and water
      contained the substance responsible for the antihistamine activity. 3. When
      assayed on the isolated guinea pig ileum, 50 mg/ml juice and 0.15 mg/ml fraction
      B produced parallel and concentration-dependent rightward displacement of the
      concentration-response curve to histamine (EC50 (FL): 1.30 (0.26-5.28) x 10(-7)
      M, 15.80 (5.90-23.30) x 10(-7) M, 12.50 (7.62-14.90) x 10(-7) M, in the absence
      and presence of 50 mg/ml juice and 12 mg/ml fraction B, respectively) apparently
      in a competitive manner. The antagonism was specific for histamine, i.e., did not
      modify the response to acetylcholine, KCl and BaCl2 and was reversible upon
      washing. Vascular permeability responses of rats to intracutaneous 1.0, 5.0 or
      10.0 micrograms histamine were decreased by about 20-25% in animals pretreated
      with 4 ml/kg of juice or with 12 mg/kg fraction B. The juice (4 ml/kg) protected
      guinea pigs from death by asphyxia induced by 5 mg histamine and the protection
      lasted at least 1 h. 4. However, since the juice was ineffective in protecting
      the gastric mucosa from histamine-induced ulceration, we conclude that the
      antihistamine effect of the juice and fraction B was produced by blockade of H1
      and not H2 receptors.

PMID- 1364162
TI  - [An update on bronchial asthma in children].

PMID- 1364165
TI  - First Robert J. Gorlin Conference on Human Dysmorphology. Minneapolis, October
      14th-15th 1991.

PMID- 1364166
TI  - Editorial comment on paper by Kantaputra and Gorlin.

PMID- 1364167
TI  - Nephrotic syndrome and respiratory allergy in childhood.
AB  - The etiology and pathogenesis of idiopathic nephrotic syndrome remain obscure.
      Several investigations have reported a role for allergy in the development and
      maintenance of this disease, especially in childhood. We have studied 20
      pediatric patients with relapses of nephrotic syndrome related in time to
      respiratory symptoms. Sensitization was demonstrated to one or more allergens in
      7 patients with episodes of proteinuria of seasonal tendency. Preventive
      management with disodium cromoglycate was successful in preventing new relapses
      in 3 patients; specific immunotherapy was assayed in another 2 without beneficial
      outcome. There appears to be a pathogenic relationship between respiratory
      allergy and proteinuria in some cases of nephrotic syndrome.

PMID- 1364168
TI  - A comparison of new nonsedating and classical antihistamines in the treatment of
      primary acquired cold urticaria (ACU).
AB  - The efficacy of the new nonsedating antihistamines loratadine and cetirizine was
      compared in a randomized, single-blind, crossover, controlled study with that of
      the classical antihistamines cyproheptadine and ketotifen in seven patients with
      primary acquired cold urticaria (ACU). The patients received each of the four
      drugs for 14 consecutive days with a 7-day interval between drugs. We evaluated
      clinical symptomatology, adverse effects, minimum time of cold contact
      stimulation required to induce an immediate coalescent wheal (CSTT), and
      inhibition of histamine-induced wheal response. Both loratadine and cetirizine
      showed suppression of symptoms with infrequent adverse effects. Important side
      effects were observed in patients receiving cyproheptadine. Improvement in CSTT
      was statistically significant for all drugs compared with baseline values,
      without differences among them. The histamine-induced skin test was significantly
      inhibited by all antihistamines. Wheal reductions were 34.6% for loratadine and
      50.9% for cetirizine. This study suggests that both loratadine and cetirizine may
      be effective in the treatment of primary ACU.

PMID- 1364169
TI  - Does C-reactive protein modulate T-lymphocyte function in methotrexate-treated
      rheumatoid arthritis patients?
AB  - Thirty-four patients with rheumatoid arthritis were treated with oral
      methotrexate for 6 months. Methotrexate was given as a single weekly dose of 7.5
      10 mg. A correlation between serum concentration of CRP and proportion of CD8+
      lymphocytes in peripheral blood was found in this group of patients. This
      correlation can be described by a linear regression equation. According to the
      results obtained, CRP suppresses lymphocyte function in patients with RA. This is
      the consequence of the stimulating effect on suppressor mechanisms.

PMID- 1364170
TI  - Sequence and secondary structure comparisons of ITS rDNA in mosquitoes (Diptera:
      Culicidae).
AB  - Sequences of the internal transcribed spacers (ITS1 and ITS2) of the mosquito
      Aedes aegypti, and the ITS2 of six related species, A. simpsoni, A. albopictus,
      A. vexans, A. triseriatus, Haemagogus mesodentatus, and Psorophora ferox are
      reported. Intraspecific variation in A. aegypti ITS1 is 1.07% among four clones
      from three individuals, and in the ITS2 is 1.17% among 15 clones from four
      individuals. In A. simpsoni, intraspecific ITS2 variation is 0.46% among 10
      clones from a single individual. Alignment of the ITS2 sequence of the seven
      species reveals several homologous domains. Secondary structure predictions for
      the ITS2 region indicate that these domains base pair to form a core region
      central to several stem features. The sequence outside the ITS2 homologous
      domains tends to be GC-rich and characteristically slippage generated; these
      areas preserve or add to the stem length of the predicted secondary structures.
      These ITS2 intraspacer variable regions resemble previously described expansion
      segments of the 28S gene region. Evolutionary analysis of the ITS2 of these
      species, using both sequence and secondary structure information, leads to the
      prediction of divergence in the mosquito tribe Aedini that is not clearly
      reflected in current taxonomic designations.

PMID- 1364171
TI  - Distinguishing between monoclonal rearrangements and allelic forms of the
      immunoglobulin lambda light chain constant region genes. Significance in the
      diagnosis of non-Hodgkin's lymphoma.
AB  - Four allelic forms of the immunoglobulin lambda light chain constant region (C
      lambda) genes are found in the caucasoid population and are recognised by the
      presence of Eco RI restriction fragments of sizes 8, 13, 18, and 23 kb
      hybridising with a C lambda probe. The less common allelic forms of the C lambda
      genes are marked by the 13, 18, and 23 kb fragments, and these may be
      misinterpreted as rearranged fragments derived from a monoclonal population of B
      cells. The 13, 18, and 23 kb alleles result from the insertion of one, two, and
      three copies, respectively, of a 5.2 kb repeat unit that can be demonstrated by
      hybridising genomic DNA digested with Hind III with a C lambda probe. Using
      selected histologically and immunophenotypically well-defined cases, we assessed
      the usefulness of the 5.2 kb Hind III/C lambda fragment in distinguishing between
      rearrangements indicative of a B-cell lymphoma and germline configurations
      representing uncommon allelic forms of the C lambda genes. From these studies, we
      conclude that Hind III digestion should routinely be performed when using the C
      lambda probe to assess B-cell monoclonality. Identification of the 5.2 kb Hind
      III fragment obviates the need to examine DNA from normal peripheral blood
      granulocytes to exclude allelism of the C lambda genes in cases exhibiting the
      uncommon restriction fragments after Eco RI digestion.

PMID- 1364172
TI  - Abnormal p53 expression in lung neuroendocrine tumors. Diagnostic and prognostic
      implications.
AB  - The diagnostic and prognostic implications of p53 immunostaining have been
      investigated in 59 pulmonary neuroendocrine tumors, including typical carcinoids
      (n = 15), so-called "atypical carcinoids" (n = 22), and small cell lung
      carcinomas (SCLCs; n = 22). Immunocytochemistry was performed on formalin-fixed,
      paraffin-embedded samples using the monoclonal antibody PAb1801, which has been
      shown to be suitable for staining fixed and embedded tissue sections. p53
      immunoreactivity was restricted to atypical carcinoids (45% of the cases being
      immunoreactive) and to SCLCs (which were positively stained in 59% of the cases),
      whereas it was consistently lacking in typical carcinoid tumors. When the group
      of the so-called "atypical carcinoids" was further reclassified, p53
      immunostaining was strictly confined to those cases belonging to the
      histologically more aggressive subsets (well differentiated neuroendocrine
      carcinoma subsets II and III). Within the same tumor type, however, p53
      immunoreactivity did not correlate with the clinical outcome of the disease and
      was not predictive of the length of survival. The data indicate that abnormal p53
      expression (which is strictly dependent on structural abnormalities of the p53
      gene) is detectable in the majority of neuroendocrine carcinomas of the lung and
      might represent a useful adjunct in the differential diagnosis of pulmonary
      neuroendocrine neoplasms, particularly in routinely fixed and embedded small
      bronchoscopic biopsies.

PMID- 1364173
TI  - Rapid in situ detection of PCR-amplified HIV-1 DNA.
AB  - The low copy number of human immunodeficiency virus 1 (HIV-1) DNA infected cells
      precludes routine detection by in situ hybridization. The inability to detect
      cells latently infected by HIV-1 makes difficult the study of factors that induce
      viral transcription, an essential factor in the development of the acquired
      immune deficiency syndrome (AIDS). A sensitive and rapid technique to detect HIV
      1 DNA could be used as a diagnostic test for AIDS and to differentiate latent
      versus active viral infection. We describe a 3-h technique whereby HIV-1 DNA is
      amplified by hot start polymerase chain reaction (PCR) and detected directly in
      infected cells. The specificity of the assay was demonstrated by double labeling
      the positive cells with CD4. Using a CR10 HIV-1-infected cell line, the 90% of
      cells that were HIV-1 DNA positive could be distinguished from the 10% that were
      actively expressing HIV-1 RNA. The PCR in situ technique should allow for the
      direct localization of DNA sequences in cells that would otherwise be
      undetectable by conventional in situ analysis.

PMID- 1364174
TI  - Identification of donor melanoma in a renal transplant recipient.
AB  - A patient with chronic renal failure received a closely matched cadaveric kidney.
      Approximately 3 months after transplantation, the patient developed a metastatic
      malignant melanoma. A large retroperitoneal mass consisting of large pleomorphic
      polygonal neoplastic cells was found close to the donated kidney. This tumor was
      diagnosed as a malignant melanoma. DNA analysis of this tumor, the donated
      kidney, and the recipient indicated that the melanoma originated from the donor.
      Although this is not the first report of a donated melanoma, it is the first
      report of definitive DNA analysis of the origin of the malignant cells.

PMID- 1364177
TI  - The acquisition of a memory phenotype by murine CD4+ T cells is accompanied by a
      loss in their capacity to increase intracellular calcium.
AB  - During the process of aging, the fraction of CD4+ T cells with a naive phenotype,
      that is, Pgp-1- CD45RBHighMEL-14+, decreases in favor of CD4+ T memory cells.
      Total CD4+ T cells from aged mice displayed a diminished calcium response to anti
      CD3 and even ionomycin as compared to the cells from young mice, and this was
      related to the changed composition of the CD4+ T-cell population. Regardless the
      age of the donor mice, naive CD4+ T cells effectively increased intracellular
      calcium, whereas memory CD4+ T cells were impaired in this regard. In addition, a
      heterogeneity in the differentiation stage of the naive CD4+ T cells was shown by
      the observation that calcium mobilization in naive CD4+ T cells from young mice
      was more profound than that in their aged counterparts. These data thus indicate
      that during the acquisition of a memory phenotype, murine CD4+ T cells lose the
      capacity to increase intracellular calcium, which in turn may be responsible for
      the decreased level of IL-2 production by these cells.

PMID- 1364178
TI  - Childhood stressors, parental expectation, and the development of schizophrenia.

PMID- 1364176
TI  - Induction of apoptosis in thymocytes by prostaglandin E2 in vivo.
AB  - In vivo administration in mice of a synthetic analog of prostaglandin E2 (PGE2)
      caused a selective and dramatic decrease of CD4+CD8+ double-positive, CD3/T-cell
      receptor-alpha beta(lo) cells in the thymus. This loss was corticosteroid
      independent and not affected by Cyclosporin A. The disappearance of CD4+CD8+
      thymocytes was strictly correlated with the induction of apoptosis inside the
      thymus as shown by morphological studies and by the induction of intracellular
      transglutaminase expression. Considering that PGE2 has been found to be produced
      by different cell populations inside the thymus, these results indicate that PGE2
      may act as endogenous signals for apoptosis during T-cell differentiation.

PMID- 1364179
TI  - Animal models of anxiety: a critical review.

PMID- 1364180
TI  - Neurochemical mechanisms of memory control.
AB  - Modulation of memory trace retrieval in emotiogenic brain structures, cortex and
      brainstem reticular formation by postsynaptic noradrenergic and dopaminergic
      drugs was found. At the initial stage of latent inhibition-a most significant
      mechanism of information selection-memory trace retrieval is retarded in all
      structures and in the cortex and the zona incerta later on. A haloperidol model
      of latent inhibition was obtained. Most important role of dopaminergic system in
      latent inhibition was shown. Inhibition of the GABA-benzodiazepine-ionophore
      complex by the blockade of GABA-receptors induced by bicuculline, the chloride
      channels by picrotoxin, the benzodiazepine receptors by flumazenil (R015-1788)
      and R015-3505 facilitates the memory trace retrieval damaged by amnesic agent.
      The dopaminergic activation enhances the dominant state and developes conditions
      for switching on the interferential GABA-ergic inhibition.

PMID- 1364181
TI  - Antihypertensive drugs and cardioprotection.
AB  - Cardioprotection is a broad term; this short review deals with six aspects: 1.
      Secondary prevention of myocardial infarction (MI) has been shown for beta
      blockers in both early and late intervention studies. Dihydropyridine calcium
      antagonists are associated with an excess incidence of coronary events, whereas
      non-dihydropyridines prevent reinfarction provided left ventricular (LV) function
      is adequate; dihydropyridines tend to increase heart rate and stimulate the
      sympathetic and renin-angiotensin systems. 2. Primary prevention of MI has been
      shown for beta-blockers in younger/middle-aged hypertensives but not in the
      elderly. Diuretics, by contrast, possibly increase the risk of coronary events in
      younger/middle-aged hypertensives but significantly reduce coronary events in
      older hypertensives. These results might be explained by the larger, noncompliant
      left ventricle of the elderly hypertensive, which, in the absence of overt
      ischemia, responds poorly to beta-blockade (further enlargement with increased
      wall stress and impaired coronary reserve), while diuretics have the opposite
      effect. Primary prevention of coronary events in patients with chronic angina is
      likely to occur with beta-blockers, while studies with calcium antagonists have
      shown a significant excess of coronary events. 3. Ischemic events occurring
      during the "vulnerable" period between 7 and 10 AM (when sympathetic activity is
      maximal) are significantly reduced by beta-blockers but not by calcium
      antagonists. 4. Stress-induced myocardial necrosis in humans is markedly reduced
      by beta-blockers. 5. Coronary risk factors, such as elevated blood lipids,
      hyperglycemia, and insulin resistance, are possibly adversely affected by
      diuretics and beta-blockers, with the former also increasing heart rate, plasma
      renin activity, and plasma catecholamine levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364182
TI  - Do we need more beta-blockers?

PMID- 1364175
TI  - [H2 antagonists as inhibitors of cytochrome P-450 in rat liver: in vitro and in
      vivo effects].
AB  - Cytochrome P-50 is a well known participant in the metabolism of xenobiotics as
      well as an activator or inactivator of hepatotoxic substances and carcinogenic
      agents. H2 antagonists, cimetidine, famotidine and ranitidine were used to
      inhibit cytochrome P-450 in rat liver. After 200 mg cimetidine, 85% inhibition of
      cytochrome P-450 in vitro and 50% in vivo were demonstrated through demethylation
      of aminopyrine. Inhibition was further confirmed by differential absorption
      spectra (Type II). The percentage inhibition obtained with famotidine or
      ranitidine were lower than those obtained with cimetidine. Inhibition of the
      microsomal oxidative system by cimetidine could lead to decreased production of
      superoxide radicals and protection against damage induced by toxic agents
      activated in the liver.

PMID- 1364183
TI  - The Gulf War Crisis: What Israel Learned about Community Health Needs.
      Proceedings of a conference. Jerusalem, Israel, March 18, 1991.

PMID- 1364184
TI  - Synopsis of seminar on community aspects of emergency situations, Assaf Harofeh
      Hospital, May 1, 1991.

PMID- 1364185
TI  - Therapy of a case of psychotic personality organization manifesting gender
      identity disorder.
AB  - The author relates his experience with a case of psychotic personality
      organization manifesting transsexualism spanning about 10 years. This paper
      presents the case and discusses the psychodynamics together with the course of
      therapy. The patient was a case of primary transsexualism who fell into
      hallucinatory-delusional states each time he seriously tried to become a woman.
      His transsexual wish was identification with his idealized grandmother image, for
      defense of his helpless and vulnerable self, and an attempt to reestablish his
      self which was facing a crisis of disintegration due to disorganization of his
      ego. Over about 4 years of psychoanalytic psychotherapy, the conflict between
      "becoming a woman" and "taking over as head of the house" was an integral issue.
      The psychotherapy was brought to a tentative conclusion by the patient giving up
      the idea of "becoming a woman" and deciding to "take over as head of the house".

PMID- 1364186
TI  - Progression of HIV-infection: markers or determinants.

PMID- 1364187
TI  - The effect of jejunal nutrition on pancreatic exocrine function.
AB  - Pancreatic juice was continuously diverted from the Wirsungial duct by
      nasopancreatic drainage of the remnant of the gland after pylorus preserving
      partial pancreato-duodenectomy in 14 patients. On the 7th postoperative day with
      stabilized pancreatic secretion the juice was collected in 10 min fractions,
      while interdigestive secretory phases of the parenchyma were established by
      volume changes. At the beginning of a phase, 100 ml slightly hyperosmolar (400
      mOsm/l) oligopeptide diet with 360 kJ (90) kCal) was given as a bolus injection
      to another 7 patients or 60 min infusion into the second jejunal loop by fine
      needle catheter jejunostomy to another 7 patients. Pancreatic water, bicarbonate,
      protein, chymotrypsin, peak amylase levels, and integrated secretory responses
      were measured. It was observed that infusion of the diet did not disturb cycling
      interdigestive phases and did not increase peak and integrated outputs. Bolus
      administration interrupted interdigestive phases and stimulated pancreatic water,
      bicarbonate, protein, chymotrypsin and amylase outputs nonparallelly. On the
      basis of the data it was concluded that pancreatic secretion seems to be well
      preserved without duodenal regulatory mechanisms, and continuous jejunal infusion
      feeding seems to be useful in pancreatic disease and in other postoperative
      states when pancreas has to be put into rest.

PMID- 1364189
TI  - [Dopaminergic receptors, multiple targets for neuroleptics].

PMID- 1364188
TI  - The effect of early postoperative nutrition on exocrine pancreatic function.
AB  - Subsequent to pancreato-duodenectomy with preservation of the pylorus in 12
      patients the effect of parenteral and enteral nutrition on pancreatic secretion
      were compared. The pancreatic juice was continuously diverted from the Wirsung
      duct by nasopancreatic drainage. Postoperative feeding was administered by fine
      needle catheter jejunostomy in 7 patients and 5 patients received total
      parenteral nutrition. The pancreatic juice was collected in four-hour fractions
      and it was analysed for volume, bicarbonate, protein, chymotrypsin and amylase.
      It has been found that on the first two days after the operation there was a slow
      increase in the measured values and on the third postoperative day after an
      abrupt rise the pancreatic secretion became steady. No differences in exocrine
      pancreatic secretion were observed between the enteral and parenteral methods of
      feeding. According to these data the two methods seem to be of the same value in
      the postoperative therapy.

PMID- 1364191
TI  - Isometric developed tension and histopathology of myocardium of chagasic mice.
      II.
AB  - In a preceding paper we reported the evolution of chagasic cardiopathy in mice
      inoculated with low number of T. cruzi from 2 days to 75 days post-infection
      (p.i.). The present work analyzed the contractility, pharmacological response and
      histopathology of myocardium isolated from chronic chagasic mice from 90 days
      until 180 days. p.i. Myocardium contractile force reached values similar to
      controls until 165 days p.i. From this to the end contractility was significantly
      lower. At 90 days p.i. NE provoked negative inotropic effect or had no effect in
      13% of the cases tested. The others had a reactivity to NE similar to normal
      ventricles. From 105 days until 180 days p.i. NE induced to a positive inotropic
      effect significantly lower than in normal. ACh effect was significantly smaller
      from 165 days to the end. Previously ACh ventricles responses were as control.
      The effects of dibenamine, propranolol and atropine (10-6M) on chagasic
      ventricles were similar to those observed in normal tissues. At 90 days p.i. the
      histopathology showed focalized inflammatory infiltrates. At 180 days p.i. fibers
      fragmentations and loss of typical striated characteristic of cardiac tissue. The
      abnormal pharmacological response described could be attributed to alterations in
      cardiac beta and muscarinic receptors probably due to a lower oxygen support. The
      present paper shows that during chronic Chagas' disease myocardial function and
      pharmacological reactivity are seriously and definitively compromised.

PMID- 1364190
TI  - [Schizophrenia and immunity].
AB  - In schizophrenia, various modifications of the immune system have been reported.
      A decrease of interleukin-2 production by T lymphocytes and an increase of IL-2
      receptors were observed by several authors. Not only cellular but humoral
      immunity seems to be modified: apart from the viral hypothesis, an auto-immune
      hypothesis holds that auto-antibodies may play a role in the biology of
      schizophrenia. Natural auto-antibodies, preexisting any antigenic stimulation,
      may also be involved, particularly in the response to neuroleptic drugs.

PMID- 1364192
TI  - Presynaptic calcium signals during neurotransmitter release: detection with
      fluorescent indicators and other calcium chelators.
AB  - Synthetic calcium buffers, including fluorescent calcium indicators, were
      microinjected into squid 'giant' presynaptic nerve terminals to investigate the
      calcium signal that triggers neurotransmitter secretion. Digital imaging methods,
      applied in conjunction with the fluorescent calcium indicator dye fura-2, reveal
      that transient rises in presynaptic calcium concentration are associated with
      action potentials. Transmitter release terminates within 1-2 ms after a train of
      action potentials, even though presynaptic calcium concentration remains at
      micromolar levels for many seconds longer. Microinjection of the calcium buffer,
      EGTA, into the presynaptic terminal has no effect on transmitter release evoked
      by single presynaptic action potentials. EGTA injection does, however, block the
      change in calcium concentration measured by fura-2. Therefore, the calcium signal
      measured by fura-2 is not responsible for triggering release. These results
      suggest that the rise in presynaptic calcium concentration that triggers release
      must be highly localized to escape detection with fura-2 imaging. Unlike EGTA,
      microinjection of BAPTA--a calcium buffer with an equilibrium affinity for
      calcium similar to that of EGTA--produces a potent, dose-dependent, and
      reversible block of action-potential evoked transmitter release. The superior
      ability of BAPTA to block transmitter release apparently is due to the more rapid
      calcium-binding kinetics of BAPTA compared to EGTA. Because EGTA should bind
      calcium within a few tens of microseconds under the conditions of our
      experiments, the inability of EGTA to block release indicates that transmitter
      release is triggered within a few tens of microseconds after the entry of calcium
      into the presynaptic terminal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364193
TI  - Presynaptic calcium concentration microdomains and transmitter release.
AB  - n-Aequorin J, a luminescent protein which responds to calcium concentration
      changes in the order of several hundred micromoles, was injected into the
      preterminal fiber in the squid giant synapse. The activation of the presynaptic
      terminal leading to release of transmitter was accompanied by light emission at
      well-defined sites at the active zone in the presynaptic terminal. Location of
      these light emission sites was very much the same from one stimulus to the next,
      indicating that light emission was triggered by the inward calcium current
      occurring at specific and invariant locations. The distribution, size and number
      of these QEDs (quantum emission domains) coincides well with the location and
      number of active zones in the presynaptic terminal. The results imply that
      transmitter release is triggered by very well-localized calcium concentration
      changes that may be as high as several hundred micromoles.

PMID- 1364194
TI  - Sodium, calcium and exocytosis: confessions of calcified scientists.
AB  - Stimulated exocytotic secretion from nerve endings is initiated by an increase in
      intracellular free calcium concentration. We summarize here our latest findings
      regarding the temporal relationship between depolarization, elevation of [Ca2+]i
      and exocytosis in single vertebrate neuroendocrine nerve endings. In addition, we
      present surprising findings for a regulatory role of intracellular Na+ on
      exocytosis.

PMID- 1364195
TI  - Synergistic regulation of cytosolic Ca2+ concentration by somatostatin and alpha
      1-adrenergic agonists in mouse astrocytes.
AB  - The effects of somatostatin and alpha 1-adrenergic receptor agonists on cytosolic
      Ca2+ in striatal astrocytes from the embryonic mouse in primary culture have been
      investigated by microfluorimetry. Methoxamine or somatostatin induced a
      transitory increase in cytosolic Ca2+, but their combined addition led to a
      sustained increase in cytosolic Ca2+ which seems to be due to a Ca2+ influx since
      it was not observed in the absence of external Ca2+. Voltage-independent Ca2+
      channels contribute to this process. Indeed, voltage-operated calcium channels
      are not involved since neither dihydropyridines nor La3+ were effective in
      suppressing the sustained cytosolic Ca2+ elevation. Moreover, depolarization by
      50 mM KCl, which was ineffective alone, suppressed the effect of somatostatin
      observed in the presence of the alpha 1 agonist, methoxamine. The implication of
      arachidonic acid in the observed potentiation is suggested by the following
      observations: 1) arachidonic acid induced a sustained elevation of cytosolic Ca2+
      similar to that evoked by the co-application of methoxamine and somatostatin; 2)
      the addition of ETYA, an inactive and non-metabolizable analogue of arachidonic
      acid suppressed the calcium plateau produced by the agonists. In addition, direct
      activation of PKC by an exogeneous diacylglycerol analogue allowed somatostatin
      alone to evoke a sustained elevation of cytosolic Ca2+. Therefore, methoxamine
      through the successive activation of PLC and PKC could allow a lipase, probably
      PLA2, to be stimulated by somatostatin. Since arachidonic acid has already been
      shown to trigger the opening of K+ channels and the formation of inositol
      phosphates, somatostatin, through the arachidonic acid-mediated hyperpolarization
      could increase the Ca2+ driving force and thus improve Ca2+ influx through the
      inositol phosphate gated channels.

PMID- 1364197
TI  - Comparison of the effect of midazolam or vecuronium on blood pressure and
      cerebral blood flow velocity in the premature newborn.
AB  - The effect of midazolam and vecuronium on mean arterial pressure (MAP) and mean
      cerebral blood flow velocity (MCBFV) was evaluated in premature infants
      (birthweight 550-2,560 g; gestational age 26-36 weeks) randomised to receive
      either 0.1 mg/kg midazolam (n = 7) or 0.05 mg/kg vecuronium (n = 8)
      intravenously. MAP, by means of an indwelling arterial catheter, and MCBFV, by
      means of non-invasive pulsed-Doppler of the middle cerebral artery, were measured
      every 5 min, starting at 10 min prior to until 1 h after drug administration. A
      transient 25-43% decrease in MCBFV (mean 0.06 m/s) dependent on a 8-23% decrease
      in blood pressure (mean 9 mm Hg) was noted in all patients within 15 min
      following administration of midazolam, which returned to baseline values within 1
      h. In 2 out of 7 infants, a plasma expander was required. In contrast, vecuronium
      only decreased the MCBFV in 3 of 8 infants. Thus, a bolus of midazolam
      transiently decreased blood pressure and MCBFV, and should be used cautiously in
      sick preterm infants.

PMID- 1364196
TI  - Enkephalin biosynthesis is coupled to secretory activity via transcription of the
      proenkephalin A gene.
AB  - The molecular mechanisms regulating neuropeptide and secretory protein
      biosynthesis in neuroendocrine cells were examined using the prototype
      neuropeptide and secretory proteins enkephalin and chromogranin A (CGA).
      Treatment with the secretogogue nicotine results in the calcium-dependent
      secretion of enkephalin peptides from bovine chromaffin cells in primary culture
      and a concomitant increase in enkephalin peptide biosynthesis. Both secretion and
      biosynthesis are also stimulated by cell depolarization with elevated potassium.
      Elevation of intracellular cyclic AMP, on the other hand, results in stimulation
      of enkephalin biosynthesis and long-term, but not acute, secretion of enkephalin
      peptides. Coupling of enkephalin biosynthesis to calcium influx occurs at the
      level of transcription of the enkephalin gene. Thus, potassium depolarization
      causes a calcium-dependent elevation of enkephalin mRNA which is preceded by an
      increase in the rate of transcription of the enkephalin gene in the chromaffin
      cell. The accumulation of enkephalin message or peptide by potassium
      depolarization or treatment with nicotine is prevented by D600 or hexamethonium
      respectively, added 1 h after addition of nicotine or KCl and following acute
      release, suggesting that calcium acts as a continuous rather than triggering
      stimulus for enkephalin biosynthesis. Sequence analysis of the bovine enkephalin
      promoter identified sequence conservation of three enhancers previously reported
      in the human gene which are required for regulation of the gene by calcium, cAMP,
      and phorbol ester in vitro. In contrast to the regulation of the enkephalin
      system, no increase in either CGA or CGB mRNA or gene transcription attended
      depolarization-induced secretion from chromaffin cells. Since enkephalin and CGA
      are co-stored in and co-released from the same secretory vesicles in these cells,
      the results imply that a surplus of CGA is constitutively synthesized in
      chromaffin cells such that compensatory up-regulation during changes in the
      secretory state of the cell, such as occurs for enkephalin, is not required for
      the secretory proteins.

PMID- 1364199
TI  - Proceedings of the IV International Congress on Malaria and Babesiosis. Rio de
      Janeiro, Brazil, 13-17 August 1991.

PMID- 1364198
TI  - Food sources of crabhole mosquitoes collected in Guajaibon Forest, Havana
      Province, Cuba.

PMID- 1364200
TI  - The Pf332 gene codes for a megadalton protein of Plasmodium falciparum asexual
      blood stages.
AB  - We characterized the Plasmodium falciparum antigen 332 (Ag332) which is
      specifically expressed during the asexual intraerythrocytic cycle of the
      parasite. The corresponding Pf332 gene has been located in the subtelomeric
      region of chromosome 11. Furthermore, it is present in all strains so far
      analyzed and shows marked restriction length fragment polymorphism. Partial
      sequence and restriction endonuclease digestion of cloned fragments revealed that
      the Pf332 gene is composed of highly degenerated repeats rich in glutamic acid.
      Mung been nuclease digestion and Northern blot analysis suggested that the Pf332
      gene codes for a protein of about 700 kDa. These data were further confirmed by
      Western blot and immunoprecipitation of parasites extracts with an antiserum
      raised against a recombinant clone expressing part of the Ag332. Confocal
      immunofluorescence showed that Ag332 is translocated from the parasite to the
      surface of infected red blood cells within vesicle-like structures. In addition,
      Ag332 was detected on the surface of monkey erythrocytes infected with Plasmodium
      falciparum.

PMID- 1364203
TI  - South American monkeys in the development and testing of malarial vaccines--a
      review.
AB  - South American Aotus and Saimiri monkeys, which are susceptible to infection with
      human malarias, have been used to develop models for the testing of human malaria
      vaccines. Studies indicate that blood-stage and sporozoite vaccines can be tested
      in these monkeys using appropriate strains of parasites.

PMID- 1364201
TI  - Transmission immunity in malaria: reflections on the underlying immune mechanisms
      during natural infections and following artificial immunization.
AB  - Malaria transmission-blocking immunity has been studied in natural malarial
      infections in man, during infections in animals and following artificial
      immunization of animals with sexual stage malaria parasites. Effective immunity,
      which prevents infectivity of a malarial infection to mosquitoes, has been
      observed under all of these circumstances. Two general types of effector
      mechanism have been identified. One is an antibody mediated mechanism which acts
      against the extracellular sexual stages of the parasite within the midgut of a
      blood feeding mosquito. The other is a cytokine mediated mechanism which
      inactivates the gametocytes of the parasites while still in the circulation of
      the vertebrate host. Both effects have been observed during natural infections
      and following artificial immunization. The basis of induction of transmission
      blocking immunity, including the nature of the memory for such immunity, however,
      may be very different in different host/parasite systems and during natural
      infection or following artificial immunization. Following artificial immunization
      a strong immune memory for transmission blocking immunity has been observed in
      animal systems. By contrast, following natural infections in man immune memory
      for transmission blocking immunity has been found to be weak and short lived if
      it occurs at all. It is suggested that the immunogens which induce natural
      transmission blocking immunity may be CD4+ independent.

PMID- 1364205
TI  - CD4+ lymphocyte involvement in ocular Behcet's disease.
AB  - Despite extensive study, the pathogenic mechanisms of Behcet's disease remain
      uncertain. The ocular inflammation caused by this disease is severe, often
      causing significant visual loss and, although the nature of the cellular
      infiltrate has been examined in many of the involved organs, the infiltrating
      cells in inflamed eyes have not. To investigate the mechanisms involved in
      perpetuating the ocular inflammation, five enucleated eyes from patients with
      Behcet's disease were examined by immunohistochemical staining using a panel of
      monoclonal and polyclonal antibodies. Control eyes from patients with chronic
      intraocular inflammation from other causes were also examined. Cellular
      infiltrates were a consistent finding in choroid and periretinal scar tissue,
      formed almost entirely by mononuclear cells. T lymphocytes were found to
      predominate (largely the CD4+ subset). B lymphocytes and NK cells were infrequent
      findings but macrophages were present in significant numbers. No complement or
      immunoglobulin deposits were found. Infiltrating lymphocytes and macrophages were
      HLA DR positive. Retinal vascular and retinal pigment epithelium were only
      occasionally positive. Our findings suggest that cell mediated immunity, rather
      than immune complex deposition is responsible for the perpetuation of the ocular
      inflammation in Behcet's disease and that CD4+ T lymphocytes play a central role
      in this.

PMID- 1364202
TI  - T cell responses to repeat and non-repeat regions of the circumsporozoite protein
      detected in volunteers immunized with Plasmodium falciparum sporozoites.
AB  - The design of a malarial vaccine based on the circumsporozoite (CS) protein, a
      major surface antigen of the sporozoite stage of the malaria parasite, requires
      the identification of T and B cell epitopes for inclusion in recombinant or
      synthetic vaccine candidates. We have investigated the specificity and function
      of a series of T cell clones, derived from volunteers immunized with Plasmodium
      falciparum sporozoites, in an effort to identify relevant epitopes in the immune
      response to the pre-erythrocytic stages of the parasite. CD4+ T cell clones were
      obtained which specifically recognized a repetitive epitope located in the 5'
      repeat region of the CS protein. This epitope, when conjugated to the 3' repeat
      region in a synthetic MAPs construct, induced high titers of antisporozoite
      antibodies in C57BL mice. A second T cell epitope, which mapped to aa 326-345 of
      the carboxy terminal, was recognized by lytic, as well as non-lytic, CD4+ T cells
      derived from the sporozoite-immunized volunteers. The demonstration of CD4+ CTL
      in the human volunteers, and the recent studies in the rodent model (Renia et
      al., 1991; Tsuji et al., 1990), suggest that CS-specific CD4+ T cells, in
      addition to their indirect role as helper cells in the induction of antibody and
      CD8+ effector cells, may also play a direct role in protection against sporozoite
      challenge by targeting EEF within the liver.

PMID- 1364204
TI  - Molecular biological approaches to the study of vectors in relation to malaria
      control.
AB  - To a large extent, control of malaria vectors relies on the elimination of
      breeding sites and the application of chemical agents. There are increasing
      problems associated with the use of synthetic insecticides for vector control,
      including the evolution of resistance, the high cost of developing and
      registering new insecticides and an awareness of pollution from insecticide
      residues. These factors have stimulated interest in the application of molecular
      biology to the study of mosquito vectors of malaria; focussing primarily on two
      aspects. First, the improvement of existing control measures through the
      development of simplified DNA probe systems suitable for identification of
      vectors of malaria. The development of synthetic, non-radioactive DNA probes
      suitable for the identification of species in the Anopheles gambiae complex is
      described with the aim of defining a simplified methodology which is suitable for
      entomologist in the field. The second aspect to be considered is the development
      of completely novel strategies through the genetic manipulation of insect vectors
      of malaria in order to alter their ability to transmit the disease. The major
      requirements for producing transgenic mosquitoes are outlined together with the
      progress which has been made to date and discussed in relation to the prospects
      which this type of approach has for the future control of malaria.

PMID- 1364207
TI  - Single-breath carbon monoxide diffusing capacity: effect of body size and age in
      healthy nonsmoking Chinese.
AB  - Because of unanswered questions about reference values for single-breath carbon
      monoxide diffusing capacity (DLCO) in Chinese, standardized DLCO measurements
      were carried out in a selected sample of 257 healthy nonsmoking Chinese aged 20
      70 years. The methods of measurement essentially followed the American Thoracic
      Society (ATS) recommendations. The measured DLCO was corrected to a standard
      hemoglobin value. Observed mean values for DLCO were 25.87 +/- 5.64 mL/min/mmHg
      in men and 21.16 +/- 3.88 mL/min/mmHg in women. Correlations of DLCO indices with
      anthropometric variables revealed that DLCO was best correlated with age in both
      sexes (r = -0.71 for men and r = -0.61 for women, p < 0.001). For alveolar volume
      (VA), the most significant correlation was found with height. For specific
      diffusing capacity (DLCO/VA), there was a significant negative relationship with
      age. Reference equations using age and body surface area (BSA) as independent
      variables for DLCO, VA and DLCO/VA were derived separately for men and women. An
      analysis of the distribution of residuals was Gaussian with simple linear
      regressions. Predicted values for DLCO and VA, as estimated in the present study,
      were much lower than equations derived from Caucasian populations. On the
      contrary, DLCO/VA values, as predicted by the present set of equations, were
      comparable to those of Caucasian equations. Therefore, differences in DLCO values
      between Chinese and Caucasians may be explained by differences in lung volume
      rather than by ethnic variations in the inherent characteristics of the alveolar
      capillary membrane. Predicted values for Chinese should be obtained from
      equations established from this study rather than extrapolated from those of
      Caucasians. The results of this study will be of value to clinical laboratories
      dealing with pulmonary function testing for Chinese patients.

PMID- 1364206
TI  - Results of therapy for beta-thalassemia major.
AB  - During the last 10 years, 92 transfusion-dependent beta-thalassemia patients have
      been encountered at the National Taiwan University Hospital and Provincial
      Taoyuan General Hospital. Seventy-seven of them were followed up regularly. Long
      term results of conventional therapy in 63 cases and allogeneic bone marrow
      transplantation (BMT) in 14 cases are reported. The conventional therapy included
      regular red cell transfusion and desferrioxamine iron chelation therapy.
      Preliminary results of conventional therapy showed a mortality of 7/63 (11%). Of
      those who were alive, the morbidity was 56/56 (100%). There was no disease-free
      survival (0/56; 0%). BMT was performed after preparatory regimens of busulfan,
      cyclophosphamide, and/or total body or lymphoid irradiation. Preliminary results
      of BMT showed a mortality of 5/14 (36%). For those who were alive, the morbidity
      was 3/9 (33%), and the disease-free-survival rate was 6/9 (67%) during a follow
      up period of three to six years. It is concluded that the only way to cure beta
      thalassemia major at present is BMT. However, the risks of BMT and donor non
      availability make conventional therapy unavoidable. Further study is needed to
      decrease the risk of BMT and to improve the efficacy of conventional therapy.

PMID- 1364208
TI  - Age trends in lung cancer.
AB  - To investigate the relationship between the stages of cancer development and the
      age trends in histologic type found at the time of disease diagnosis, we studied
      1,669 patients with histologically proven lung cancer. These patients were
      examined at the National Taiwan University Hospital using Mantel-Haenszel Chi
      square testing to determine a linear trend. These patients were divided into
      three age groups: group 1 (< 45 years), 141 patients (8%); group 2 (45-64 years),
      946 patients (57%); group 3 (65 years or more), 582 patients (35%). The ratio of
      men to women was 1.4 in group 1, 2.5 in group 2 and 2.3 in group 3. In men, there
      was a significant trend for the proportion of squamous cell carcinoma to increase
      from 26% to 42% and that of adenocarcinoma to decrease from 52% to 34% as age
      increased. In women, an age trend for histologic type was not observed. There was
      also a significant trend for local-stage squamous cell carcinoma in men to
      increase from 18% in group 1 to 35% in group 2 and to 42% in group 3. In men, but
      not in women, local-stage large cell carcinoma increased from 20% in group 1 to
      31% in group 2 and to 64% in group 3. However, the age-stage trend for other cell
      types was not significant in men.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364209
TI  - Clinical manifestations of bronchogenic carcinoma.
AB  - A retrospective clinical study was carried out on 227 pathologically proven cases
      of bronchogenic carcinoma from eastern Taiwan, between October 1986 and March
      1990. The ratio of males to females was low (2.15:1). The most common cell type
      was adenocarcinoma (39.2%), with squamous cell carcinoma (36.1%) being the second
      most common. Adenocarcinoma contributed to 51.4% of the bronchogenic carcinoma in
      women and 33.5% in men. History of cigarette smoking was strongly associated with
      squamous cell carcinoma and small cell carcinoma. The most common symptom was a
      cough (69%). The majority of small cell carcinoma and squamous cell carcinoma
      appeared to be of the central type in location while most adenocarcinoma appeared
      to be of the peripheral type. Bronchoscopic examination was the most valuable
      method for confirming the diagnosis of bronchogenic carcinoma. Most patients
      presented late and only 19 cases (8.4%) underwent surgery. Aborigines have a
      lower risk of developing bronchogenic carcinoma. The clinical manifestations of
      bronchogenic carcinoma in eastern Taiwan are similar to those found in Taiwan as
      a whole.

PMID- 1364210
TI  - Cytomorphometric and flow cytometric analysis of bladder transitional cell
      carcinoma using acridine orange fluorochrome: correlation with histopathology and
      clinical behavior.
AB  - Cell material from 79 cases of archival paraffin-embedded tumor specimens of
      newly diagnosed transitional cell carcinomas of the urinary bladder was studied
      retrospectively using rapid flow cytofluorometric DNA analysis. The male to
      female ratio was 62/17. The mean age at diagnosis was 65.3 +/- 10.8 years.
      Clinical characteristics, including survival, recurrence and progression were
      closely related to the histopathologic grading and tumor staging. The tumors were
      classified as diploid (DI = 0.9-1.1) or aneuploid. Total aneuploid occurrence was
      46%. The aneuploid frequency for the various tumor grades was 25% for grade 1,
      37% for grade 2 and 78% for grade 3. Stages Ta (O) and Tl (A) tumors differed
      from muscle-invasive tumors (T2-4) in that they had a lower frequency of
      aneuploid occurrence (34%, 41% vs 50%, 73%, and 75%). Multiple aneuploid stem
      cell lines had no influence on tumor grade or stage. The DNA ploidy was closely
      related to the five-year survival rate, the probability of tumor recurrence and
      progression. On the contrary, the modal nuclear size of the tumor cells had no
      correlation with histopathology or the clinical characteristics. Bladder tumors
      of an intermediate grade (grade 2) may be subdivided into two groups with
      different outcomes on the basis of flow cytometric characteristics. It is
      concluded that DNA flow cytometry can serve as an additional prognostic parameter
      for bladder cancer patients in addition to conventional histopathology.

PMID- 1364211
TI  - Total cavopulmonary connection for surgical treatment of complex congenital heart
      disease.
AB  - Diversion of vena caval flow directly into the pulmonary circulation--total
      cavopulmonary connection--has been tried at our hospital for two years as an
      alternative to the modified Fontan procedure for surgical treatment of complex
      congenital heart disease other than tricuspid atresia in 26 cases with six
      operative mortalities. The causes of death were low cardiac output in four,
      uncontrollable paroxysmal supraventricular tachycardia in one and airway
      obstruction in one. Except for one late death which occurred three months after
      surgery due to sepsis, the 19 patients who survived the operation were followed
      up for four to 27 months (mean 15 months). All of them improved clinically (NYHA
      Class 1). Graded bicycle exercise tests were performed in five of them at three
      to 12 months after surgery, and their exercise tolerance was comparable to that
      of patients with an atriopulmonary connection. In conclusion, total cavopulmonary
      connection is an acceptable alternative to the modified Fontan operation for
      surgical treatment of complex congenital heart disease, although longer follow-up
      is necessary.

PMID- 1364212
TI  - Endoscopic approaches in the diagnosis of obstructive jaundice--with special
      reference to endoscopic retrograde cholangiopancreatography.
AB  - Duodenofiberscopy with endoscopic retrograde cholangiopancreatography (ERCP) was
      performed in 102 patients with obstructive jaundice. Peritoneoscopy and
      peritoneoscopic cholecystocholangiography were done in patients whose ERCP was
      inconclusive. The causes of obstructive jaundice were carcinoma of the pancreas
      in 14 cases, carcinoma of the papilla of Vater in 12 cases, choledocholithiasis
      in 37 cases, carcinoma of the common bile duct in seven cases, hepatocellular
      carcinoma (HCC) in seven cases, intrahepatic cholestasis in three cases and
      miscellaneous causes in eight cases. No final diagnosis was made in 14 patients.
      The duodenofiberscopic examination with biopsy revealed the cause of obstructive
      jaundice directly in eight cases, when carcinoma of the pancreas or papilla of
      Vater extended to the duodenal mucosal surface. In 34 of the 37 patients with
      choledocholithiasis, ERCP alone was successful in making the diagnosis.
      Percutaneous transhepatic cholangiography and ERCP were used together to reach a
      diagnosis in the remaining three patients. We propose a classification for HCC on
      ERCP which may be useful for the study of icteric type HCC.

PMID- 1364213
TI  - Adjunctive choledochoduodenostomy to choledocholithotomy in the treatment of
      calculous biliary tract disease.
AB  - Between 1986 and 1991, 16 selected patients with calculous biliary tract disease
      (CBTD) underwent side-to-side choledochoduodenostomy (CDS) as an adjunct to
      either primary (10 patients) or secondary (six patients) choledocholithotomy.
      Patients selected for adjunctive CDS were those with common bile duct dilatation
      > or = 1.5 cm in size. All operations were elective procedures. The stoma of the
      CDS was about 3.0 cm in size, measured directly. There were no operative deaths.
      There were no early complications related to the CDS procedure itself, except for
      two (12.5%) wound infections. CDS significantly eliminates bile stasis which is
      indicated by a fall in both the serum levels of alkaline phosphatase (from 228 +/
      118 to 72 +/- 22 IU/L, p < 0.01) and total bilirubin (from 4.7 +/- 4.7 to 0.9 +/
      0.2 mg/dL, p < 0.01) postoperatively. Late complications (ascending cholangitis
      or sump syndrome) of CDS or recurrent symptoms of CBTD were not encountered
      during the average follow-up period of 21 +/- 18 months. From our clinical
      results, we suggest that adjunctive CDS to choledocholithotomy is a safe and
      effective procedure in the treatment of selected patients with CBTD.

PMID- 1364214
TI  - Molecular cloning and sequence analysis of an isolate of hepatitis C virus from
      Southern California, U.S.A.
AB  - We obtained a cDNA clone representing a partial RNA sequence of a human hepatitis
      C virus (HCV) isolate from Southern California. RNA was extracted from the liver
      tissue of a patient with post-transfusion hepatitis, and used for cDNA synthesis
      and polymerase chain reaction (PCR) amplification using oligonucleotide primers
      specific for the prototype HCV RNA. The cDNA clone obtained contains 585 base
      pairs of HCV sequences and represents the region encoding the putative
      nonstructural protein NS3 of HCV. Sequence analysis of this clone showed that it
      shares 93.8%, 78.7% and 79.6% similarity, respectively, with the previously
      published American, Japanese and Taiwanese isolates at the nucleotide level,
      indicating the heterogeneity of HCV RNA in different geographic areas. By
      contrast, it shares 97.3%, 92.9% and 92.9% with these respective isolates at the
      amino acid level, suggesting the functional conservation of viral genes.

PMID- 1364215
TI  - Reduced glutathione, superoxide dismutase contents and malondialdehyde formation
      in platelets from uremic patients: relation to plasma and platelet zinc.
AB  - Platelet-reduced glutathione (GSH), superoxide dismutase (SOD) and zinc content
      as well as malondialdehyde (MDA) formation were studied in 55 healthy volunteers
      as controls and 49 patients with chronic renal failure. Uremic patients had a
      significantly lower GSH and SOD content as well as an abnormal MDA formation in
      their platelets. Their plasma zinc level was sharply below the normal value, but
      their platelet zinc content was similar to that of normal controls. We also found
      that the plasma zinc and platelet zinc level was positively correlated to the
      platelet GSH content in normal controls and uremic patients. Therefore, the
      results suggest that in uremic patients the decrease in platelet antioxidant
      agents (GSH and SOD) may be partially related to their low plasma zinc level.

PMID- 1364216
TI  - Bedtime intermediate-acting insulin in the treatment of secondary failure to oral
      hypoglycemic agents.
AB  - Low-dose bedtime insulin therapy in combination with oral hypoglycemic agents
      (OHAs) has become an alternative treatment for NIDDM subjects with secondary
      failure to OHA. To assess its clinical efficacy, patient compliance, and its
      possible side effects, 33 patients with secondary OHA failure were recruited in
      this study. All of the subjects had experienced poor glycemic control for at
      least six months on their maximal OHAs before the institution of the bedtime
      insulin injection. Monotard HM (human insulin zinc suspension) was given at an
      initial dose of 0.15-0.2 U/kg body weight and was adjusted thereafter. As a
      whole, low-dose bedtime insulin with OHAs improved glycemic control. According to
      the clinical response, 10 patients (30.3%) were graded as responders, 12 (36.4%)
      were partial responders, 10 (30.3%) were non-responders, and one (3%)
      discontinued insulin therapy. There was no difference in demographic features
      among these three groups of patients. During this period, eight (25%) cases
      experienced mild hypoglycemic symptoms. In conclusion, combination of OHAs with a
      low-dose bedtime insulin injection is an alternative therapy for NIDDM patients
      with OHA failure.

PMID- 1364218
TI  - Birth weight by gestational age in twin pregnancies: analysis of 661 pairs.
AB  - The mortality of twin infants is four to five times higher than that of
      singletons, and one-half to two-thirds of all twins weigh < 2,500 g at birth. The
      appropriate interpretation of fetal growth throughout pregnancy is dependent upon
      the availability of adequate standards. We reviewed 661 pairs of live twin
      infants born at Chang Gung Memorial Hospital from 1979 to 1990. The frequency of
      twin births was 1.17% (1:86), and the ratio of males to females was 1.03. The
      frequency of preterm births (< 37 weeks) was 36.9%, the frequency of low birth
      weight (< 2,500 g) was 47.9% and very low birth weight (< 1,500 g) was 6.7%. A
      fetus grows most rapidly from the 32nd to the 35th week of gestation (200 g per
      week). The growth was 145 g per week from the 28th to the 32nd week and from the
      35th to the 38th week of gestation. After the 38th week, the mean birth weight
      increased by only 35 g per week. Compared with a singleton birth, the mean birth
      weight of twins was about 100 g lighter during the 28th to the 32nd week, then
      the difference increased gradually to about 500 g at term.

PMID- 1364217
TI  - Pseudomonas aeruginosa isolated from corneal ulcer: susceptibility to
      antimicrobial agents tested alone or in combination.
AB  - Twenty-eight isolates of P. aeruginosa from corneal ulcers were tested for their
      susceptibility to 19 antimicrobial agents by an agar dilution method. The effect
      of a combination of an aminoglycoside with a beta-lactam, ciprofloxacin or
      colistin was checked by the checkerboard titration method. The minimal inhibitory
      concentrations (MICs) of these antimicrobial agents varied greatly. The MICs of
      aminoglycosides were near the breakpoint value of the usual susceptibility
      definition in most tested strains, but some were highly resistant. Ciprofloxacin,
      imipenem, aztreonam, ceftazidime, cefoperazone, piperacillin and colistin were
      other effective drugs with low MICs. Piperacillin, ceftazidime or aztreonam in
      combination with gentamicin or amikacin revealed a synergistic effect, but
      antagonism was found with ciprofloxacin or colistin combined with gentamicin or
      amikacin. Considering the difference in drug concentration achievable between
      systemic administration and topical application, the MIC quantitative
      determinations and the combination effect of antimicrobial agents against ocular
      isolates could provide useful information to ophthalmologists in choosing drugs
      for treatment of P. aeruginosa ocular infections.

PMID- 1364219
TI  - Isokinetic and isometric testing of knee musculature in young female patients
      with patellofemoral pain syndrome.
AB  - By using a Cybex II+ isokinetic dynamometer, we performed isokinetic and
      isometric tests of the knee musculature in 29 female patients (aged 17-45 years)
      with patellofemoral pain syndrome (PFPS) and the same number of age- and weight
      matched female controls. The pain was unilateral in 11 patients and bilateral in
      18. The isokinetic testing was set at speeds of 60 degrees, 120 degrees and 180
      degrees/sec; the isometric testing was set at 30 degrees and 60 degrees of knee
      flexion. The results showed that the lowest torque values occurred on the
      affected side of the unilateral group, followed by both sides of the bilateral
      group, the sound side of the unilateral group, and the control group,
      sequentially. The highest rate of abnormal torque values for all PFPS patients
      occurred in the quadriceps at 60 degrees/sec of isokinetic contraction: 33%. In
      this study, five (17%) patients showed abnormal torque curves and 10 (34%)
      patients complained of pain or soreness at either the lowest speed of isokinetic
      testing or during the isometric testing of the quadriceps muscles. The bilateral
      torque difference was highest in the unilateral group.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1364220
TI  - Detection of hemoglobin E heterozygotes by using polymerase chain reaction and
      direct DNA sequencing: report of a case.
AB  - From an overseas Chinese born in Thailand, an extraordinarily high level of A2 +
      E band (20.2%) was found during routine cellulose acetate Hb electrophoresis.
      With a suspicion of Hb E, the beta-globin gene was studied by using the
      polymerase chain reaction (PCR) and direct DNA sequencing method. A 1.4 kb
      fragment covering the whole beta-globin gene was amplified by PCR. Sequence
      analysis of the amplified product revealed a GAG > AAG transversion at codon 26,
      which resulted in an amino acid substitution of lysine for glutamic acid. A
      normal sequence at the corresponding codon was noted in the other allele; hence,
      this patient is a heterozygote of Hb E. PCR and direct DNA sequencing provide a
      rapid method for detection of Hb E from a small amount of DNA.

PMID- 1364221
TI  - Mycotic aneurysm rupture: report of four cases.
AB  - "Mycotic" aneurysm was originally described by Osler in 1885. It occurs in a
      normal or atherosclerotic artery from septic emboli in patients with infective
      endocarditis. However, now the term "mycotic" aneurysm is applied to all cases of
      aneurysms caused by any organisms. From September 1988 to November 1990, four
      cases of ruptured mycotic aneurysm were diagnosed at our institute. Three were
      males and one was a female; they were elderly with atherosclerosis of the aorta.
      The diagnosis was established by computed tomography (CT) scan, bacteriology or
      operative findings. Two of the patients underwent emergency operation; only one
      survived. In general, the diagnosis of mycotic aneurysm is based on the classical
      features of fever, abdominal or chest pain, positive blood culture and a
      pulsatile mass. Because the clinical manifestations are often variable, a patient
      may present with chronic sepsis (esp. Salmonella sp) of unknown origin with
      deterioration to a fatal outcome from the aneurysmal rupture, which is a rare
      cause of retroperitoneal abscess or pericardial effusion. The principles of
      management, including high clinical suspicion, an accurate diagnosis by imaging
      studies (arteriography or CT scan), prolonged effective antibiotic therapy,
      arterial ligation or wide excision of the infected lesion, intraoperative Gram's
      stain and culture, extra-anatomic bypass grafting through clean tissue planes,
      and prolonged postoperative follow-up, are indispensable to reduce morbidity and
      mortality.

PMID- 1364222
TI  - Spontaneous spinal epidural hematoma: report of seven cases.
AB  - From July 1984 to June 1990, seven cases of spontaneous spinal epidural hematoma
      (SSEH) were studied. The common clinical pictures in these cases were rather
      typical with an apoplectic onset of severe spinal pain followed in hours (median:
      four hours) by signs of progressive spinal cord compression. All cases underwent
      myelography and computed tomographic (CT)-myelographic studies which showed in
      all cases a block by a posterior extradural lesion in the spinal column; however,
      the correct diagnosis of SSEH was made preoperatively in only three cases. The
      neurologic deficits prior to surgery were complete or nearly complete paraplegia
      in five cases and a high grade of paraparesis in the other two. The median
      interval of paralysis or paresis before surgery was 28 hours. The final outcome
      was evaluated by the grade of functional recovery, and the following were found
      to be the favorable factors: 1) incomplete preoperative neurologic deficits; 2) a
      slow course of clinical progression, especially a long duration of pain before
      the onset of paralysis; 3) no delay in surgery; 4) involvement of short spinal
      segments; and 5) lumbosacral lesions. Particular emphasis is made on early
      diagnosis and prompt surgery for a favorable outcome.

PMID- 1364223
TI  - Histiocytosis X with thyroid involvement: report of a case.
AB  - Histiocytosis X is a disease of histiocyte proliferation in response to some
      unknown etiology. Thyroid involvement is extremely rare in the literature. In
      this paper, we present an 18-year-old female with histiocytosis X with thyroid
      involvement. This patient had had a goiter with normal thyroid function since 12
      years of age. A thyroidectomy was done under the suspicion of thyroid cancer.
      Pathology revealed histiocytosis X. Hypoparathyroidism and hypothyroidism were
      noted after the operation and were treated with thyroid hormone, vitamin D and
      calcium carbonate. This patient also had lesions on the left side of mandible, in
      the suprasellar region and possibly in the right mastoid. A curettage biopsy of
      her mandibular lesion was also compatible with histiocytosis X. She was proven to
      have hypothalamic and pituitary dysfunction including hypogonadism and
      hypoadrenalism. Her thyroid lesion did not recur after the thyroidectomy. The
      toothache that she had also experienced subsided after the curettage biopsy of
      the mandibular lesion. Hypothalamic and pituitary dysfunction were controlled by
      hormone replacement. Because her disease had been running a benign clinical
      course, no chemotherapy was given.

PMID- 1364224
TI  - Adult-onset, autosomal dominant, rimmed vacuolar myopathy with limb-girdle
      distribution--a preliminary report.
AB  - Adult-onset, autosomal dominant myopathy with limb-girdle distribution in a
      Chinese family is reported. Nine members were affected with characteristic
      proximal weakness and pelvifemoral-preceded scapulohumeral involvement. The
      facial, extraocular and bulbar muscles were spared. Rimmed vacuoles were the most
      obvious characteristics in the myopathologic study of the biopsy specimens from
      four patients. In a review of the previous literature, we found three reported
      families with clinical and myopathologic features identical to ours, and these
      families are viewed as a distinct subgroup of myopathy.

PMID- 1364225
TI  - Nosocomial outbreak of scabies.
AB  - Scabies is a common infestation caused by the human itch mite Sarcoptes scabiei.
      Small outbreaks in communities or hospitals are not uncommon, but are rarely
      documented. In this paper, we report on a nosocomial outbreak of scabies
      originating from a patient with Norwegian scabies at the Intensive Care Unit in
      Taiwan Provincial Tainan Hospital. Twenty-nine individuals including four
      inpatients and 25 hospital personnel were involved. The diagnosis was based on
      history, clinical findings or a positive skin scraping. Unfamiliarity with the
      clinical manifestations delayed the diagnosis and the highly contagious nature of
      Norwegian scabies precipitated this outbreak. Early initiation of effective
      control measures with extensive therapeutic and prophylactic treatment of all
      contacts resulted in successful eradication of the outbreak.

PMID- 1364226
TI  - Assessment of the association of HLA-DR 3/4 heterozygotes with diabetes mellitus
      and non-diabetic diseases.
AB  - To evaluate the disease association with HLA-DR 3/4 heterozygotes, 1,074
      subjects, who had been analyzed consecutively for HLA-DR antigens for organ
      transplantation or to study the disease association with HLA from June 1984 to
      June 1986, were enrolled in this study. Of these subjects, 278 had diabetes, 168
      were healthy controls or donors, and 628 had other diseases. Of the 1,074
      subjects, 35 subjects (3.2%) were DR 3/4 heterozygotes and 1,039 subjects (96.7%)
      were non-DR 3/4 heterozygotes. Among the 35 DR 3/4 positive subjects, 23 were
      diabetic (65.7%), two were healthy donors (5.7%), 10 had other diseases (28.5%)
      such as recurrent abortion (n = 3), hepatoma (n = 2), Graves' disease (n = 1),
      idiopathic hypoparathyroidism (n = 1), IgA nephropathy (n = 1), uveitis (n = 1)
      and gout (n = 1). Among the 23 DR 3/4 positive diabetics, 19 (82.6%) had insulin
      dependent diabetes mellitus (IDDM), three (13.0%) had non-insulin-dependent
      diabetes mellitus (NIDDM), and one (4.3%) had maturity onset diabetes of the
      young (MODY). When these DR 3/4 positive diabetics were compared with the other
      disease and control/donor groups, significant increases in the relative risk were
      seen for IDDM patients (RR = 32.61, 43.80, respectively, p < 0.001). No
      significant association could be seen for NIDDM and MODY patients. In those non
      diabetic patients positive for DR 3/4, there was no significant association with
      DR 3/4 heterozygotes. These findings suggest that: 1) DR 3/4 positive subjects
      are highly associated with IDDM; and 2) there is no significant association of DR
      3/4 with NIDDM, MODY and other non-diabetic diseases.

PMID- 1364227
TI  - The effect of third-trimester glycemic control on maternal and perinatal
      morbidities in pregestational diabetes mellitus.
AB  - From May 1974 to March 1989, 48 cases of pregestational diabetes mellitus treated
      during the third trimester of pregnancy at the Obstetric Clinic of the National
      Taiwan University Hospital had complete maternal-fetal chart, and were enrolled
      into this retrospective review. Of these cases, 28 were class B, 13 were class C
      and seven were class D-R. The maternal complications and perinatal morbidities of
      each class were reviewed. The mean fasting, postprandial plasma glucose
      concentrations and the mean excursion of plasma glucose levels were calculated
      for statistical analysis. Among the maternal complications, urinary tract
      infections and preterm labor were significantly associated with mean fasting
      plasma glucose concentrations. Among perinatal morbidities, neonatal respiratory
      distress and metabolic problems (including neonatal hyperbilirubinemia,
      symptomatic hypoglycemia, hypocalcemia and polycythemia) were significantly
      associated with mean plasma fasting glucose concentrations, and perinatal
      asphyxia was associated with a mean excursion of plasma glucose levels. In view
      of the paucity of knowledge about the etiology of complications in diabetic
      pregnancies, it is necessary to conduct a prospective multi-center study with
      well-characterized morbidities to search for the role of glycemic control in
      obstetric and perinatal complications.

PMID- 1364228
TI  - gamma-Glutamyltranspeptidase and dipeptidyl peptidase IV activity in the serum of
      normal and hepatoma-bearing chickens and in the plasma membranes from liver and
      hepatoma Mc-29.
AB  - Investigations on the activity of gamma-glutamyltranspeptidase (GGT) and
      dipeptidyl peptidase IV (DPP IV) in the serum of healthy chickens and those
      bearing hepatoma Mc-29, and in liver and hepatoma plasma membranes were carried
      out. There was no difference in the serum enzyme activities of control and tumor
      bearing chickens but the activity of GGT was twice higher and that of DPP IV 20
      times lower in hepatoma plasma membranes than in chicken liver plasma membranes.
      Using thin-layer analytical isoelectric focusing in agarose gels it was
      established that the pI range of GGT from host serum and hepatoma plasma
      membranes was shifted to more acidic values. This could be interpreted as a
      specific feature for this enzyme considered as a tumor marker.

PMID- 1364229
TI  - Action of tiazofurin and 8-Cl-cAMP in human colon and pancreatic cancer cells.
AB  - Tiazofurin and 8-Cl-cAMP are novel chemotherapeutic agents shown to be effective
      against various cancer cells in vitro and in vivo. They act through distinct
      mechanisms that might modulate the signal transduction pathway, which causes
      growth inhibition, differentiation and down-regulation of c-ras and c-myc
      oncogene expression. We examined the effects of tiazofurin and 8-Cl-cAMP on
      colony formation of HT-29 human colon cancer and BxPC-3 and PANC-1 human
      pancreatic cancer cell lines. The IC50 of 8-Cl-cAMP was 0.1 and 0.2 microM in the
      pancreatic and colon cancer cell lines, respectively, and tiazofurin yielded
      IC50s from 4 (PANC-1) to 18 microM (HT-29). Simultaneous incubation with 8-Cl
      cAMP and tiazofurin had additive effects on the inhibition of colony formation in
      the three examined cell lines. These results indicate possible clinical
      usefulness of a combination of tiazofurin and 8-Cl-cAMP in the treatment of colon
      and pancreatic carcinomas.

PMID- 1364230
TI  - Comparison of transcranial Doppler with DSA in vertebrobasilar ischaemia.
AB  - To determine the role of transcranial doppler (TCD) in the evaluation of the
      vertebrobasilar circulation, we compared the results of TCD with intraarterial
      digital subtraction angiography (DSA) in 20 patients with vertebrobasilar
      ischaemia (VBI). TCD had a sensitivity of 87%, a specificity of 80%, a positive
      predictive value of 93% and a negative predictive value of 67%. It was also able
      to give functional data when combined with arteriography and correctly identified
      the main pathology in 92% of those with abnormal TCD and angiogram. The 2
      patients with false negative TCD had vertebral artery occlusion, which may be
      missed because of the signal from adjacent arteries. TCD may be a useful
      screening method in patients with VBI for the detection of large vessel occlusive
      disease of the intracranial vertebrobasilar system. It is important to remember
      that proximal vertebral artery stenoses will be missed by TCD.

PMID- 1364231
TI  - Proceedings of the IIIrd International Symposium on Schistosomiasis and the IIIrd
      National Meeting on Schistosomiasis. Recife, Brazil, 20-25 October 1991.

PMID- 1364233
TI  - Annual Meeting of the Hungarian Society for Microbiology. Szekesfehervar, July 7
      9, 1992. Abstracts.

PMID- 1364232
TI  - Establishment of an MT4 cell line persistently producing infective HIV-1
      particles.
AB  - Human T cell Lymphotropic Virus-I (HTLV-I) carrying human T cell line MT4 is
      highly sensitive to Human Immunodeficiency Virus-1 (HIV-1). After HIV-1 infection
      cell clusters characteristic of intact MT4 rapidly disintegrate, syncytia appear
      and the cells die. Surviving MT4 cells were subcultured following HIV-1 infection
      of high multiplicity. We succeeded to establish an MT4 cell line continuously
      producing infective HIV (MT4/HIV-1). The original and the HIV-1 infected MT4
      cells were morphologically similar. The MT4/HIV-1 cells proved to be nearly 100%
      positive in indirect immunofluorescence assay using the serum of an HIV-1
      antibody positive individual. OKT4 surface antigen could not be demonstrated on
      MT4/HIV-1 cells. On electron microscopic pictures typical and atypical virus
      particles could be seen near the surface of the cell membrane. The persistently
      produced virus particles were infective for H9 and MT4 cells. The antigenic
      structure of the virus produced by MT4 cells was similar to that produced by H9
      cells.

PMID- 1364234
TI  - Pharmacological agents used in implant dentistry. Parts II and III.

PMID- 1364235
TI  - Advances and Perspectives in Reproductive Endocrinology of Domestic Animals.
      Symposium proceedings. Olsztyn, Poland, August 30-September 2, 1992.

PMID- 1364236
TI  - Some neurovegetative correlates of Minnesota Multiphasic Personality Inventory
      (MMPI)
AB  - In 57 patients with psicovegetative disorders and abnormal MMPI, abnormality in
      MMPI scales indicating hypochondriasis, hysteria, gender deviant, paranoia,
      psychastenia, schizophrenia, hypomania or introversion was accompanied by
      increased plasma catecholamine levels and/or responses to hypoglycemia or by an
      increased cardiovascular reactivity. A high depression scale was associated with
      lower plasma catecholamine levels. Blunted plasma growth hormone responses to
      hypoglycemia were found in abnormal hypomania scale, and augmented responses of
      plasma cortisol in abnormal hysteria or schizophrenia scales. Paranoia and
      hypomania traits correlated with absence of morning-evening differences in blood
      cortisol levels. Electrodermal responses compatible with increased sympathetic
      activity correlated with high hysteria, gender, paranoia, schizophrenia or
      hypomania MMPI scales. This study indicates that most psychopathological traits
      in MMPI are accompanied by humoral and/or electrophysiological signs of
      abnormality of the autonomic nervous system.

PMID- 1364237
TI  - [The effect of a protein-free diet on insulin and somatostatin secretion in
      rats].
AB  - We have used a model of experimental protein-energy malnutrition induced in
      weaned rats by administration of a protein free diet during 2 weeks. Some
      malnourished rats were then refed with a control diet for 4, 9 or 30 days.
      Control rats were fed for the same periods with the balanced control diet.
      Malnourished rats showed a loss in body weight of approximately 25%. After 30
      days of refeeding, the animals gained weight reaching values higher than that of
      control rats. Insulin secreted by perifused pancreatic slices from malnourished
      rats, was impaired in first and second glucose-induced secretory phases. Basal
      secretion was also diminished in incubation of pancreatic slices. When
      malnourished rats were refed for 4 days, basal insulin secretion reached control
      values. Stimulated insulin secretion was normalized at 9 and 30 days of
      refeeding. Our result on somatostatin (SRIF) secretion in malnourished rats
      showed basal hypersecretion and diminished first and second glucose-induced
      secretory phases. During refeeding basal SRIF secretion was normalized from day
      4. On the contrary stimulated secretion was significantly increased at 4 and 9
      days of refeeding, and on day 30 values did not differ from controls. In protein
      energy malnutrition, the disturbed hormonal state can represent adaptative
      mechanisms to the protein depletion and hormonal changes have also an essential
      role in refeeding.

PMID- 1364238
TI  - [Current surgical aspect of primary hyperparathyroidism (100 years after F. D.
      Von Recklinghausen)].
AB  - The "Association Francaise de Chirurgie" asked to authors an update on primary
      hyperparathyroidism based on a retrospective multicentric study on 4883 patients
      operated on by 79 surgeons. Aim of this study was an update on clinical and
      biological aspects, localizing studies, and therapeutic aspects with their
      results. There were 3418 females (70%) and 1465 males (30%) mean age 53 years (9
      to 91 years): 3702 solitary adenomas (75.8%), 720 multi-glandular lesions (14.7%)
      92 multiple endocrine neoplasias (1.9%) and 86 carcinomas (1.8%). None lesions
      was found in 283 cases (5.8%). To day, diagnosis is most often made on fortuitous
      hypercalcemia. Localising studies showed sensibility less than 50%. Surgery was
      successful in 92.7%. Mortality occurred in 0.6% hypoparathyroidism in 3.8%,
      laryngeal palsy in 1.5% and hematomas in 0.45%. In conclusion this study shows
      the changes regarding the diagnosis, the uselessness of localizing studies before
      first cervicotomy, and the good results of surgery. Autotransplantation and
      cryopreservation allow reducing of hypoparathyroidism.

PMID- 1364240
TI  - Symposium on Structure, Function and Product of Genes. The 5th Kitasato Research
      Conference. July 18, 1992. Abstracts.

PMID- 1364239
TI  - Quantitative immunohistochemical distributions of tyrosine hydroxylase and
      calmodulin in the brains of spontaneously hypertensive rats.
AB  - Immunohistochemical distributions of tyrosine hydroxylase and calmodulin in the
      rat forebrain were analyzed quantitatively as a possible model for the
      hypertension mechanism. The brain slices of spontaneously hypertensive rats (SHR)
      at 12 weeks of age were stained immunohistochemically for tyrosine hydroxylase
      and for calmodulin, and the distributions and amounts of these proteins were
      measured at 40-microns intervals by a fluorescence microphotometry system in
      comparison with those in normotensive control, Wistar Kyoto rats (WKY, the parent
      strain of SHR). Tyrosine hydroxylase levels in the neostriatum, nucleus
      accumbens, nucleus septi lateralis and tractus diagonalis, and calmodulin levels
      in the medial part of the neostriatum of SHR were lower than those in WKY. We
      reported previously that the decrease of the serum calcium level in SHR causes a
      decrease of the dopamine levels in the neostriatum and nucleus accumbens regions
      through a calmodulin-dependent system, and subsequent low levels of dopamine in
      the brain which may produce an increase in blood pressure. Combining this finding
      and our previous reports, we also suggest that the lower dopamine levels seen in
      the neostriatum and nucleus accumbens regions of SHR may result from the decrease
      in tyrosine hydroxylase and/or calmodulin levels in these regions in addition to
      the abnormality of calcium metabolism, and low levels of dopamine may produce an
      increase in blood pressure through functions of cerebral dopaminergic neurons and
      peripheral sympathetic nerves.

PMID- 1364243
TI  - Scandinavian Sarcoidosis Association, 1st conference. Stockholm, March 28, 1992.
      Proceedings and abstracts.

PMID- 1364241
TI  - Advantages and problems with benzodiazepine sedation.

PMID- 1364244
TI  - Therapy for acute myocardial infarction: an update.

PMID- 1364245
TI  - Proceedings of the 1992 International Symposium on Public Health Surveillance.
      Atlanta, Georgia, April 22-24, 1992.

PMID- 1364242
TI  - Postoperative pain control for dental and oral surgery.

PMID- 1364246
TI  - Short-term immunosuppression enhances long-term survival of bovine chromaffin
      cell xenografts in rat CNS.
AB  - Xenogeneic donors, a largely untapped resource, would solve many of the problems
      associated with the limited availability of human donor tissue for neural
      transplantation. Previous work in our laboratory has revealed that xenografts of
      isolated bovine chromaffin cells survive transplantation into the periaqueductal
      gray (PAG) of immunosuppressed adult rats. Electron microscopic analysis reveals
      that graft sites contain healthy chromaffin cells, but do not contain host immune
      cells typical of graft rejection. The aim of the current study was to assess the
      necessary conditions for long-term survival of bovine chromaffin cell xenografts
      in the central nervous system (CNS). In particular, the need for short-course vs.
      permanent immunosuppressive therapy with cyclosporine A (CsA) for the long-term
      survival of grafted bovine chromaffin cells was addressed. Grafts from animals
      receiving continuous CsA treatment for either 3, 6, or 12 wk contained large
      clumps of dopamine-beta-hydroxylase (DBH) positive cells in contrast to the few
      surviving cells observed in nonimmunosuppressed animals. In addition, grafts from
      animals that had CsA treatment terminated at 3 or 6 wk contained similarly large
      clumps of DBH-positive cells. Furthermore, short-term immunosuppression (3 wk)
      appeared to enhance the long-term survival of grafted cells, since clumps of DBH
      staining cells could still be positively identified in the host PAG at least 1 yr
      after transplantation. Complete rejection of graft tissue depends on several
      factors, such as blood-brain barrier integrity, the presence of major
      histocompatibility complex (MHC) antigens in either the host or graft, and the
      status of the host immune system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364247
TI  - 1st International Congress of The Cell Transplant Society. Pittsburgh,
      Pennsylvania, May 31-June 3, 1992. Abstracts.

PMID- 1364248
TI  - Neuropsychological and psychiatric correlates of intractable pseudoseizures.
AB  - Psychogenic seizures can mimic convulsive epilepsy and with repetitive attacks,
      iatrogenic complications from aggressive treatment of status epilepticus can
      occur. We studied neuropsychiatric features of 20 patients in whom psychogenic
      seizures were intractable and at times continuous. Nineteen of 20 patients seen
      were female, and all but one were under 40 years of age. All had convulsive
      attacks resistant to various medications, normal neurological examinations, and
      negative imaging studies and electroencephalograms (EEGs). Sixteen had previous
      evidence of epilepsy and the other four had epileptic relatives. Seizures were
      atypically prolonged, included back arching and pelvic thrusting, and persisted
      despite intravenous diazepam and therapeutic phenytoin and phenobarbital levels.
      Seizures terminated spontaneously in five, were stopped by suggestion in four,
      and persisted until respiratory arrest or elective intubation in 11. Ten patients
      had conversion disorder, six borderline or mixed personality disorder and four
      mental retardation. Fifteen had had some precipitating stressor and the remainder
      had histories of exhibiting attention-seeking behaviour. Nine of 10 patients with
      conversion disorder had 'conversion V' Minnesota Multiphasic Personality
      Inventory (MMPI) profiles, while personality disorder patients had elevation of
      several psychopathological scales. Patients with conversion disorder gradually
      improved with anticonvulsant discontinuation, while retarded individuals were
      helped by behaviour modification, situational change or neuroleptics. Personality
      disorder patients continued to have attacks and eventually discontinued follow
      up. Clinical evidence of non-epileptic seizures includes clinical atypicality and
      long duration, exacerbation by medications and frequent attacks despite normal
      examination and studies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364249
TI  - [Japanese clinical statistical data of patients with Buerger's disease].

PMID- 1364250
TI  - [Japanese clinical statistical data of patients with irritable bowel syndrome].

PMID- 1364251
TI  - Subdural empyema--clinical experiences.
AB  - The authors present the experiences from their clinic with diagnostic and
      treating of subdural empyema. In the years 1953-1991 altogether 5 patients were
      treated with this diagnosis in the Clinic of Neurosurgery in Olomouc. Nobody of
      the patient died. There was possible to observe in all these patients before
      operation symptoms of meningeal irritation, febrilities and in 4 patients the
      neurologic focal symptomatology. The authors arrive to the conclusion, that the
      most convenient operation approach is craniotomy, which must be preferred to
      smaller surgical approaches. One part of the intracranial operation must be
      sanation of the primary inflammation leading to arising of subdural empyema. The
      regular postoperation control of the patient by means of computed tomography
      renders possible the timely detection of relapse and leads to timely surgical
      intervention.

PMID- 1364252
TI  - Lack of correlation between UV-induced enhancement of melanoma development and
      local suppression of contact hypersensitivity.
AB  - Injection of melanoma cells into the UV-irradiated ear skin of syngeneic mice
      results in an increased incidence of melanomas compared with that in
      nonirradiated ear skin. This effect of UV is localized to the site of irradiation
      and appears to be immunologically mediated. In these studies we test the
      hypothesis that the effect of UV irradiation on melanoma development is related
      to its ability to alter epidermal Langerhans cells and impair the induction of
      contact hypersensitivity. A regimen of UV irradiation that altered epidermal
      immune cells and interfered with the generation of contact hypersensitivity was
      tested for its ability to increase the incidence of melanoma. Conversely, the ear
      skin of C3H mice treated with a regimen of UV radiation that enhanced melanoma
      development was examined for the number of appearance of ATPase+ and Thy-1+
      dendritic epidermal cells and tested for the ability to initiate a contact
      hypersensitivity response. No correlation between these effects of UV irradiation
      could be detected. Furthermore, implantation of melanoma cells into UV-irradiated
      ear skin resulted in the generation of systemic immunity against subsequent tumor
      challenge. Therefore, we conclude that the ability of UV irradiation to modify
      melanoma development is unrelated to its effects on the afferent arm of the
      contact hypersensitivity response and that enhanced melanoma development is not
      due to an impairment in the induction of tumor immunity.

PMID- 1364253
TI  - Human epidermal keratinocytes are a source of soluble ICAM-1 molecules.
AB  - A soluble form of the usually membrane-bound adhesion molecule ICAM-1 was
      detected in supernatants derived from human epidermal keratinocytes.
      Specifically, supernatants harvested from long-term cultured normal human
      keratinocytes, or from the spontaneously immortalized keratinocyte cell line
      HaCaT, did not contain significant amounts of sICAM-1, but shedding of sICAM-1
      was found to be markedly induced upon stimulation of keratinocytes with rh IFN
      gamma. In contrast, cells from the two epidermoid carcinoma cell lines, KB and
      A431, constitutively shed significant amounts of sICAM-1 even without cytokine
      stimulation, and sICAM-1 contents in supernatants harvested from these cells were
      further increased upon stimulation of cells with rh IFN gamma. These studies
      indicate, that in addition to peripheral blood mononuclear cells and human
      melanoma cells, human epidermal keratinocytes constitute an important cellular
      source of sICAM-1. By binding to leukocyte LFA-1 molecules, keratinocyte-derived
      sICAM-1 may influence inflammatory responses in the skin. In addition,
      constitutive shedding of sICAM-1 by transformed human keratinocytes may represent
      a possible mechanism by which neoplastic keratinocytes escape from cytotoxicity.

PMID- 1364254
TI  - [Common bile duct calculi--current surgical approach and procedure].

PMID- 1364255
TI  - [Necrotizing-gangrenous infections of extravisceral soft tissues].

PMID- 1364256
TI  - [Lymphatic involvement in chronic venous insufficiency--a prognostic factor].

PMID- 1364258
TI  - [Original method for primary local treatment of burns with silver nitrate in
      selective coagulating concentration. Histopathologic and clinical arguments].

PMID- 1364257
TI  - [Resection or amputation in rectal ampullar cancer].

PMID- 1364260
TI  - [Morris syndrome. Clinical case report].

PMID- 1364259
TI  - [Diverticulum of the fourth section of the duodenum].

PMID- 1364261
TI  - [Esophageal motility disorders induced by anesthesia].

PMID- 1364262
TI  - [Continuous peridural anesthesia in colorectal surgery].

PMID- 1364263
TI  - [In memoriam Dr. Dumitru Burlui].

PMID- 1364265
TI  - Correspondence Re: Timothy S. Loy, Paul L. Gelven, Dawn Mullins, and Alberto A.
      Diaz-Arias. Immunostaining for P-glycoprotein in the diagnosis of thyroid
      carcinomas. Mod Pathol 5:200, 1992.

PMID- 1364264
TI  - c-erbB-2 (HER-2/neu) oncopeptide immunoreactivity in localized, high-grade
      transitional cell carcinoma of the bladder.
AB  - Monoclonal antibodies to the extracellular domain of the c-erbB-2 oncoprotein
      (p185) react with routinely processed, paraffin-embedded human tissues, and
      positive staining with these reagents has been shown to correlate with gene
      overexpression. To determine whether such antibodies would add prognostic data to
      the analysis of a pre-defined subset of transitional cell carcinoma (TCC) of the
      bladder, we studied 20 high-grade (Grade 3) TCCs from patients known to have
      limited disease (Jewett-Strong stages B1, B2, and C) and for whom at least 3-yr
      clinical follow-up was available. Data procured from this immunohistochemical
      analysis were compared with tumoral DNA content (determined by flow cytometry)
      and conventional clinicopathologic features. Overall, 13 of 20 TCC (65%) were
      reactive for p185-erbB-2. However, there was no apparent relationship between
      p185-reactivity and either DNA content, tumor stage or clinical outcome. These
      results suggest that c-erbB-2 expression may be augmented in localized high-grade
      TCC but that there is no evidence for the contention that this phenomenon has any
      effect on the biologic behavior of these neoplasms. The only factor that
      predicted a more favorable outcome was a relatively low stage at the time of
      diagnosis.

PMID- 1364266
TI  - [Peripheral facial paralysis and HIV infection. 2 case reports].
AB  - Two cases of peripheral facial paralysis in subjects with HIV infection are
      reported. On the basis of these two cases and data from the literature, the
      clinical and paraclinical features of this facial nerve lesion are described. The
      various aetiological hypotheses put forward are discussed, but it is probable
      that the paralysis results from a direct effect of the virus on the nerve. HIV
      associated peripheral facial paralysis may occur irrespective of the number of
      CD4 lymphocytes and does not seem to have a prognostic significance. However, it
      appears by preference in stages I, II and III and may then reveal the HIV
      infection.

PMID- 1364267
TI  - [Role of genetic factors in detecting essential arterial hypertension (EAHT)].

PMID- 1364268
TI  - Biological activities of Synanceja horrida (stonefish) venom.
AB  - Some biological and neurochemical properties of the venom of stonefish (Syanceja
      horrida) were investigated. The venom exhibited oedema-inducing, haemolytic,
      hyaluronidase, thrombin-like, alkaline phosphomonoesterase, 5' nucleotidase,
      acetylcholinesterase, phosphodiesterase, arginine esterase, and arginine amidase
      activities. Recalcification clotting time, prothrombin, and kaolin-cephalin
      clotting times were increased 1.7-2.3- and 2.4-fold respectively. The LD50 (i.v.
      mouse) was 300 micrograms/Kg. Its effects on uptake and stimulation of
      neurotransmitter synthesis and release were observed in rat brain synaptosomes.
      In the presence of 100 micrograms venom, uptake of [methyl-3H] choline in rat
      brain synaptosomes was inhibited 70%, while that of 4-amino-n-[U-14C] butyric
      acid was inhibited 20%. The toxin also stimulated the release of [3H]
      acetylcholine from the synaptosomes.

PMID- 1364269
TI  - A modified technique used in the preparation of mitotic chromosomes from mosquito
      larval neuroblast cells.

PMID- 1364270
TI  - Unusual mitochondrial DNA polymorphism in two local populations of blue tit Parus
      caeruleus.
AB  - Mitochondrial DNA (mtDNA) from 25 blue tits Parus caeruleus sampled from two
      populations of the Grenoble region (France) was assayed for polymorphism with 17
      restriction endonucleases. Nine genotypes were found. Several mtDNA genotypes
      were also analysed by amplification via the polymerase chain reaction (PCR) and
      direct sequencing of 903 bp of the cytochrome b gene. The mtDNA polymorphism is
      greater in P. caeruleus than in other comparable bird species and results from
      the presence of two clearly differentiated mitochondrial lineages. Using the data
      of restriction polymorphism, the mean sequence divergence between individuals of
      the two lineages is 1.23%. Therefore, P. caeruleus should fall into the category
      II of phylogeographic pattern sensu Avise et al. (1987): discontinuous mtDNA
      genotypes which co-occur in the same region. P. caeruleus, like humans and other
      mobile species with high gene flow, seems to have lost its geographic structure
      in terms of mtDNA phylogeny. This unusual mitochondrial polymorphism can be
      explained by the recent admixture of two long-term isolated populations. This
      could be accounted for by two different scenarios. One assumes a simultaneous
      post-glacial colonization of the Grenoble region by two isolated European
      populations of P. caeruleus. Alternatively, hybridization between P. caeruleus
      and P. cyanus could have caused the observed pattern of mtDNA variation.

PMID- 1364271
TI  - Conservation genetics of whales and dolphins.
AB  - Whales and dolphins (cetaceans) are found in all the world's oceans and in some
      of the major rivers, yet little is known about the distribution and behaviour of
      many species. At the same time, cetaceans are under threat from a variety of
      pressures including direct and indirect takes, pollution, and competition for
      habitat and prey. To ensure their long-term survival it will be necessary to
      preserve genetic diversity through the identification and protection of
      differentiated populations, the assessment of variation within local populations,
      and through a better understanding of reproductive and dispersal behaviour. The
      application of molecular genetic techniques is helping to provide answers to some
      of these previously intractable questions. Early results suggest few consistent
      patterns. Obvious geographic boundaries correlate to genetic distance in some
      species, and not in others. Furthermore, morphological variation within species
      can be fairly extensive without correlating to genetic distance, or relatively
      minor between morphotypes that are as genetically distinct as some species. These
      examples emphasize the need for further study.

PMID- 1364273
TI  - Prospective study with Tinset tablet.
AB  - Fifty-seven patients suffering from seasonal rhinitis have been treated with
      oxatomide (Tinset) tablets. In the well-responding cases the drug was prescribed
      for prophylactic purpose to prevent the expectable rhinitis attacks in later
      seasons. In the first season the preventive action of the drug was registered in
      a relatively high rate of the patients, but this action was significantly less
      marked in the second period. According to the opinion of the author oxatomide is
      a drug of high value both for therapeutic and preventive purposes. Nevertheless,
      the sedative action of the drug has to be taken into consideration in the course
      of therapy.

PMID- 1364272
TI  - Evolutionary history of the honey bee Apis mellifera inferred from mitochondrial
      DNA analysis.
AB  - Variability of mitochondrial DNA (mtDNA) of the honey bee Apis mellifera L. has
      been investigated by restriction and sequence analyses on a sample of 68 colonies
      from ten different subspecies. The 19 mtDNA types detected are clustered in three
      major phylogenetic lineages. These clades correspond well to three groups of
      populations with distinct geographical distributions: branch A for African
      subspecies (intermissa, monticola, scutellata, andansonii and capensis), branch C
      for North Mediterranean subspecies (caucasica, carnica and ligustica) and branch
      M for the West European populations (mellifera subspecies). These results
      partially confirm previous hypotheses based on morphometrical and allozymic
      studies, the main difference concerning North African populations, now assigned
      to branch A instead of branch M. The pattern of spatial structuring suggests the
      Middle East as the centre of dispersion of the species, in accordance with the
      geographic areas of the other species of the same genus. Based on a conservative
      2% divergence rate per Myr, the separation of the three branches has been dated
      at about 1 Myr BP.

PMID- 1364275
TI  - Transplantation in Pediatrics. Proceedings of an international symposium.
      Hannover, Germany, 18-19 January 1992.

PMID- 1364274
TI  - [Beta-blockers in the prevention of the rupture of esophageal varices. A meta
      analysis].
AB  - The meta-analysis of 5 trials for primary prevention and of 18 trials of
      secondary prevention emphasizes the effect of beta-blockers in the decrease of
      variceal bleedings in cirrhosis. Beta-blockers are reducing the bleeding events
      with 32% in the primary prevention and with 28% in the secondary prevention. The
      mortality is reduced by 15%, respectively by 23%. This is the first meta-analysis
      reported in the Romanian gastroenterological literature.

PMID- 1364276
TI  - The metabolic and circulatory response to beta-blockade in hypertensive men is
      correlated to muscle capillary density.
AB  - Both haemodynamic and metabolic variables have been shown to be related to the
      fibre composition and capillary density of skeletal muscle in man. In the present
      study, the change of several metabolic variables during beta-blockade was
      investigated and related to muscle fibre composition and capillary density in 28
      men with essential hypertension. They had been given atenolol (50 mg/day) or
      metoprolol (200 mg/day) or propranolol (160 mg/day) for 4-12 months. Serum
      triglycerides increased during treatment and individual changes were
      significantly inversely correlated with capillary density. Insulin concentrations
      in the fasting state and at the end of an i.v. glucose tolerance test were
      significantly higher during beta-blockade, and individual changes were inversely
      correlated with capillary density. Furthermore, body weight increased and heart
      rate decreased, changes that were also correlated with capillary density. It is
      concluded that many of the previously but poorly understood large interindividual
      differences in response to beta-blocker treatment may be explained by the degree
      of development of the capillary net in muscle tissue. Obesity, physical training
      as well as genetic factors are known determinants of capillary density.

PMID- 1364277
TI  - Cell injury and protection in the gastrointestinal tract: from basic sciences to
      clinical perspectives. Proceedings of the 3rd International Symposium on
      Gastrointestinal Cytoprotection. Pecs, Hungary, October 7-8, 1991.

PMID- 1364278
TI  - Resistance to medical ulcer therapy--possible reasons and management.
AB  - In 112 patients with duodenal ulcer (males, mean age 29, range 18-35) with a
      history of at least 3 years, and never being treated with H2-antagonists,
      maintenance therapy with Tagamet was started. All of them had ulcer recurrence
      when entering the study. The first two months a full dose was applied, after this
      bedtime doses up to 24 months. Endoscopy was performed at the beginning, after
      the first and second months and then every two-month period. Gastric secretion
      was measured every 2-3 months. A resistant ulcer was defined as one 1/not healing
      within the two initial months, 2/recurring on maintenance treatment. RESULTS: in
      78% the ulcer was healed within one month, in 96% within two months, in the rest
      within the following 3-4 weeks. Relapses occurred in 21 patients, altogether 27
      times. Factors likely to contribute to recurrence included a large ulcer size,
      longer duration, an inflamed mucosa and--most frequently--heavy smoking. Patients
      with relapses had higher initial secretory values and smaller decrease during
      maintenance treatment. Helicobacter pylori (examined in a subgroup) was not
      clearly associated with ulcer recurrence.

PMID- 1364279
TI  - The oxygen-centered radicals scavenging activity of sulfasalazine and its
      metabolites. A direct protection of the bowel.
AB  - Oxygen-centered radicals, such as superoxide (O2-) and hydroxyl radicals (.OH)
      generated by phagocytes have been suggested to be involved in the pathogenesis of
      chronic inflammations of the bowel, such as Crohn's disease and colitis ulcerosa.
      Recently, sulfasalazine (SASP) and its metabolites have been reported to exert
      their effects as a direct scavenger of oxygen-centered radicals in the bowel. To
      scavenge oxygen-centered radicals in vivo, however, SASP and its metabolites have
      to react with O2- and/or .OH in vitro very rapidly, furthermore they have to
      reach an appropriate (possible millimolar) concentration range at the site of
      inflammation. To test this possibility, we investigated the direct O2- and .OH
      scavenging activity of SASP and its metabolites using the specific electron
      paramagnetic resonance/spin trapping method, and we compared the 50% inhibition
      rates of SASP and its metabolites with their known concentrations in the bowel
      and in the human plasma. It was found that SASP and its metabolites, such as 5
      amino-salicylic acid (5-ASA), and acetyl-5-amino-salicylic acid (AC-5-ASA), but
      not sulfapyridine (SP) and acetyl-sulfapyridine (Ac-SP) have a direct O2- and .OH
      scavenging activity in vitro systems. Among the compounds, SASP and 5-ASA can
      reach a concentration which is appropriate to scavenge oxygen-centered radicals
      in the bowel but not in the human plasma. It was concluded that the in vivo
      antiinflammatory effects of SASP and its metabolites are, at least partly, due to
      the direct oxygen-centered scavenging activity of these drugs.

PMID- 1364280
TI  - Adequate enzymatic substitution in treating exocrine pancreatic insufficiency.
AB  - The chymotrypsin in the stool test was used to monitor adequate enzymatic
      substitution in treating exocrine pancreatic insufficiency with 18 patients (16
      suffering from chronic pancreatitis and 2 having passed duodenopancreatectomy due
      to pancreatic cancer). This test helps to identify pancreatic insufficiency and
      can be successfully used in monitoring the adequate amount of pancreatic
      substitute, which, we have found, differs from patient to patient. The dosage can
      be higher in cases of chronic pancreatitis than in those required after
      duodenopancreatectomy.

PMID- 1364281
TI  - [A new therapeutic approach tp drug-resistant schizophrenia: clozapine. Long-term
      prospective study in 16 patients].
AB  - Clozapine, a dibenzodiazepine derivative, has potent antipsychotic activity; but
      bone marrow suppression resulting in agranulocytosis has been associated with
      clozapine treatment and has restricted the administration of this drug to
      treatment-resistant schizophrenic patients. This report describes preliminary
      results of an open prospective study of the effects of clozapine on
      symptomatology and social function in 16 treatment-resistant schizophrenic
      patients. Authors prospectively followed up for 18 months 16 DSM III-R
      schizophrenic patients who had failed to respond to various neuroleptics (n: 7.2
      +/- 2.8); when clozapine treatment was initiated, the mean duration of the
      illness was 14.2 (+/- 6.7) years. Total BPRS, BPRS "positive" and "negative"
      symptoms scores were used for evaluation. Social integration and side effects
      were also studied. 14 of 16 patients are still receiving clozapine; 1 out of 14
      patients has a more than 60% decrease in total BPRS, 11 out of 14 have 30 to 60%
      decrease in total BPRS and 2 out of 14 have less than 30% decrease in total BPRS.
      Improvements in both total and positive symptoms BPRS scores were observed within
      the first month of treatment (p < 0.001); improvement in negative symptoms was
      noted within the third month (p < 0.02). At the end of the follow up period, 43%
      of patients showed marked improvement in family life and 21% found a job during
      the study. Beyond noteworthy improvement of clinical symptoms in these patients
      who presented with severe schizophrenia, clozapine also significantly reduced the
      use of concomitant medication. Side effects are studied but none required
      treatment disruption; neurological side effects were less reported than with
      usual neuroleptics. It is concluded that clozapine offers particular benefits for
      some treatment-resistant schizophrenic patients; however the increased
      comparative risk requires a restricted use of clozapine to selected patients.

PMID- 1364282
TI  - [The effect of neuroleptics in a attempt at understanding the vulnerability to
      schizophrenia].
AB  - Animal and human data suggest that neuroleptic drugs act by decreasing the
      special significance of some stimulations, especially those of importance for the
      subject. The two following hypotheses are therefore considered as a basis for the
      work presented in this paper: 1) the target of neuroleptic drugs is a neuro
      psychological mechanism whose function is to focalize the subject on important
      stimulations and to involve the subject in responding; 2) schizophrenia
      vulnerability could imply an excessive and abnormal propensity to be over
      involved, especially in existentially loaded problems. A careful clinical study
      of the mode of decrease, and sometimes of disappearance, of schizophrenic
      delusions under the influence of neuroleptic treatment confirms the hypotheses.
      Results are of interest for clinical treatment and for research.

PMID- 1364283
TI  - The effect of TSH and TSI on the thyroglobulin expression of cultured human
      thyroid cells.
AB  - Human thyroid cells in culture stimulated by TSH and TSI were used in order to
      detect thyroglobulin expression. After three days stimulation the cells were
      incubated with monoclonal thyroglobulin antibody and FITC-conjugated
      antiglobulin. Fluorescent index (the intensity of fluorescence related to hundred
      analysed cells) was estimated for each experimental group. The most effective
      stimulation of the thyroglobulin expression was detected after TSH stimulation at
      the concentration of 0.1 mU/ml. TSI from active Graves' patients provoked the
      highest expression of thyroglobulin at concentration of 1.0 mg/ml, but the
      fluorescence index was lower than after TSH stimulation. The thyroglobulin
      expression was intracellular, large, partly confluent granules were detectable
      mainly in the perinuclear area. Antigen expression on the surface of cultured
      thyroid cells could not be detected. The morphology of thyroglobulin expression
      as detected by immunofluorescence, was the same after TSH and TSI stimulation. It
      is concluded, that both stimulating factors, i.e. TSH and TSI, are involved in
      the thyroglobulin expression of human thyroid cells.

PMID- 1364284
TI  - [Magnetic resonance tomography of the sellar region in patients with endocrine
      diseases].
AB  - The authors discuss the present-day problems of radiotherapy. They show the major
      prospective trends in this field and describe the OS3Dplan system, made in this
      country, that represents a working place of a radiologist and serves for the
      development, analysis and storage of the schemes of long-distance gamma-beam
      therapy of oncologic patients. The OS3Dplan system is realized via the IBM PC/AT
      286/287 computer but can operate with any of the IBM PC/XT/AT/PS-2--8086/80486
      computers, made before 1986 with the videoadapter EGA/VGA, and functioning under
      MS-DOS, Microsoft (version 3.3 or older). The mathematical provision of the
      videodigitizer (distance control and videocamera) permit the introduction of
      videoinformation into the personal computer in the 256 x 256 format, 512 x 512
      pixels. The mathematical provision of the OS3Dplan proper permits a volume
      planning of long-distance gamma-beam therapy. This module type system will be of
      interest for various specialists (radiologists, roentgenologists, oncologists,
      students, etc.), for it permits a collection and maintenance of a data bank on
      patients with imaging of roentgenograms, CT, NM tomography, ultrasonic data on
      the computer display and printing these data, perform metric analyses and
      reconstruct the volume.

PMID- 1364285
TI  - GAP-43 as a modulator of G protein transduction in the growth cone.
AB  - Much circumstantial evidence that GAP-43 is involved in neuronal growth cone
      function has accumulated over the last ten years. The expression of the protein
      is closely correlated both temporally and spatially with periods of axonal
      outgrowth, and the protein is highly concentrated in the growth cone membrane.
      There is direct evidence that overexpression of the protein can alter cell shape.
      This review focuses on the molecular mechanisms whereby GAP-43 could exert these
      actions. One important requirement for GAP-43 function is its localization to
      appropriate regions of the cell. The ability of this hydrophilic protein to
      associate with membrane fractions is determined by a short 10 amino acid stretch
      of the amino terminus of the protein, which contains two cysteine residues
      subject to palmitoylation. Whether this region can direct growth cone targeting
      in neurons is not yet clear. Once appropriately localized, GAP-43 may modulate
      complex cellular properties such as growth cone motility, synaptic plasticity and
      neurotransmitter release. One possible molecular mechanism for these cellular
      changes in GAP-43 regulation of the GTP-binding protein, G(o). The observation
      that the growth cone membrane contains extremely high concentrations of G(o) led
      us to investigate the interaction of G(o) and GAP-43. There is evidence that G
      protein-mediated transduction systems can control the same cellular functions
      thought to be altered by GAP-43: growth cone motility, neurotransmitter release
      and synaptic plasticity. Purified GAP-43 does stimulate guanine nucleotide
      binding to G(o). Its action in stimulating GDP release is quite similar to that
      of G protein-coupled transmembrane receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364286
TI  - [Cystic dystrophy of aberrant pancreatic tissue in the duodenal wall. Diagnostic
      and therapeutic problems].
AB  - The authors report the case of a 28-year-old man with a cystic dystrophy of
      aberrant pancreatic tissue (C.D.A.P.T.) presenting with a history of major
      abdominal pain. First diagnosis was chronic pancreatitis because of clinical
      presentation, alcoholic intoxication, and the results of medical imaging
      techniques. A vagotomy associated with a gastroenterostomy was performed. Several
      years later the abdominal pain relapsed and failed to be cure by means of medical
      treatment. A duodenopancreatectomy was performed. Histology demonstrated the
      diagnosis of C.D.A.P.T. C.D.A.P.T. is a benign disease of the pancreas, limited
      to its cephalic portion, without demonstrated pathogenesis. C.D.A.P.T. can be
      either isolated or associated with a chronic pancreatitis. Clinical diagnosis can
      be particularly difficult as indicated by a literature review. Abdominal pain is
      the main symptom. Clinical presentation is rarely related to a complication
      (stenosis). Endoscopy, sonogram, and CAT scan are three techniques of diagnosis
      value, but intraluminal-sonography is more efficient. Tumor excision is not
      recommendable. Treatment of C.D.A.P.T. by duodeno-pancreatectomy (D.P.) is often
      indicated because of concurrent chronic pancreatitis or suspected pancreatic
      carcinoma. In case of clinical diagnosis of C.D.A.P.T., fenestration of the cysts
      under endoscopic control is the only local treatment that can avoid D.P.

PMID- 1364287
TI  - [Proceedings of a congress on professional risk of inhalation anesthesia.
      Brescia, 12 May 1992].

PMID- 1364288
TI  - MRI and Neuroimmunology in Multiple Sclerosis and other Leukoencephalopathies of
      Viral Origin. Proceedings of a meeting. Rome, Italy, 28-29 September 1990.

PMID- 1364290
TI  - Are we needlessly retaining 'hopeless' teeth?

PMID- 1364291
TI  - Avoid adverse forces: clinical applications of occlusion with root-form implants.

PMID- 1364289
TI  - T-cell subpopulations in pediatric healthy children: age-normal values.
AB  - Assessment of the percentage and absolute number of T cells as well as of their
      main subpopulations is presently a routine procedure for the diagnosis and follow
      up of a wide array of pediatric immunologic disorders. For several clinical
      applications (severe immunodeficiencies or leukaemias) the diagnostic usefulness
      of their enumeration does not require close comparison with age normal values,
      while in other circumstances such as follow-up of immunomodulating or
      immunosuppressive treatments or detection of minor immune defects, the expected
      changes of T cell subsets are more subtile and they are likely to be detected
      only by comparison with well-defined age normal values. In the present study CD3,
      CD4 and CD8 positive cells were enumerated in a group of 410 healthy children of
      age ranging from 30 days to 9 years. No significant changes in percentage or
      absolute number were observed during infancy and childhood. Furthermore the sum
      of CD4 and CD8 positive cells was close to the percentage of CD3 positive cells,
      suggesting a phenotype maturity of T cells from infancy.

PMID- 1364292
TI  - Occlusal considerations for implant restorations.

PMID- 1364293
TI  - Rotational accuracy of implant components for single-tooth, root-form implants.

PMID- 1364294
TI  - Add to your knowledge of implant prosthodontics by understanding the uses of
      mesostructures.

PMID- 1364295
TI  - The need to refer patients.

PMID- 1364296
TI  - Guided tissue bone generation.

PMID- 1364297
TI  - Methods for treating the failing root-form dental implant.

PMID- 1364298
TI  - The use of root-form implants for orthodontic anchorage.

PMID- 1364299
TI  - A new dimension--implant-assisted orthodontics.

PMID- 1364300
TI  - Uses and placement of porous hydroxyapatite.

PMID- 1364301
TI  - Implants for the partially edentulous.

PMID- 1364302
TI  - The tripodial subperiosteal implant for the severely atrophic mandible.

PMID- 1364303
TI  - The single tooth replacement. A thorough periodontal-prosthetic approach to
      insertion.

PMID- 1364304
TI  - Using the premaxilla as a receptor site for root-form implants with concern for
      total aesthetics.

PMID- 1364305
TI  - A new technique for the old subperiosteal implant.

PMID- 1364306
TI  - Optimizing soft tissue consistencies around transepithelial abutments.

PMID- 1364307
TI  - Implant prosthesis planning for the completely edentulous patient.

PMID- 1364308
TI  - Uses and placement of porous hydroxyapatite.

PMID- 1364309
TI  - Comparative utility of the explorer and probe in implant clinical evaluation.

PMID- 1364310
TI  - An implant alternative--the single-stage cylindrical implant.

PMID- 1364311
TI  - The Ceka Revax hybrid prosthesis; how to work with asymmetrically placed
      osseointegrated implants.

PMID- 1364312
TI  - Delivery of the 'prosthetic ready' case.

PMID- 1364313
TI  - Using the calvarial bone graft for implant reconstruction.

PMID- 1364315
TI  - The conversion prosthesis: an addition to implant preparedness.

PMID- 1364314
TI  - Implant prosthetic planning for the partially edentulous arch.

PMID- 1364316
TI  - An analysis of current approaches to implantology.

PMID- 1364317
TI  - Parafunctional habits and implant destruction.

PMID- 1364318
TI  - Enhancing implant prosthodontics with a new abutment system.

PMID- 1364320
TI  - Evaluating the effectiveness of resilient components of a root form implant
      system.

PMID- 1364319
TI  - The verification index: a nicety or necessity?

PMID- 1364321
TI  - A method for the simplification of cylindrical implant prosthodontics.

PMID- 1364322
TI  - The significance of provisionalization in implant prosthodontics.

PMID- 1364323
TI  - Accurate three-dimensional pre-surgical planning and radiographic implant
      simulations.

PMID- 1364324
TI  - Endothelial transport of macromolecules: transcytosis and endocytosis. A look
      from cell biology.

PMID- 1364327
TI  - Corneal endothelial structure and function under normal and toxic conditions.
AB  - Our understanding of the function of the corneal endothelium in corneal thickness
      regulation, and the role of ion transport mechanisms in endothelial physiology,
      has expanded greatly over the past 25 years. The basic events occurring across
      the apical and basolateral membranes of the cells are far better understood
      today, although gaps still exist in the area of the relationship of the cellular
      and paracellular pathways and their relative contribution to the overall behavior
      of the endothelium. Little is known about the movement of ions or fluid between
      the cells or in what proportion this may occur compared to the cellular events.
      Furthermore, although our knowledge of the ionic movement processes has been
      enhanced, the link between fluid transfer across the endothelium and ion
      movements remains an enigma. Important questions also remain concerning the link
      between electrical characteristics and either ion movement or fluid transport.
      Improved storage solutions are needed that will preserve endothelial function
      after transplantation through the provision of a significant improvement in long
      term cell survival. The limit to preservation time at present is about 14 days,
      and the use of other variables in the storage solution may extend this time. In
      reality, however, extension of preservation time is now of secondary importance
      relative to the need to enhance cell survival and reduce cell loss following
      surgery. Whether such improvement can be made with manipulation of the solution
      alone, or whether refinements are needed in the surgical technique awaits further
      study. Our comprehension of the biochemical linkage between energy supply and ion
      movement also remains uncertain in view of the particular intracellular
      localization of the anionic ATPases to mitochondrial loci. Despite numerous
      attempts there have been only a few chemicals identified that stimulate the fluid
      pump, but the level of stimulation has been relatively small and short-lived. No
      sustained effects have been found that would be of clinical benefit in reducing
      corneal thickness. A considerable variety of chemicals has been tested on the
      endothelium and it is unlikely that any new compounds will be identified that
      will cause enhancement of the fluid pump that would be of clinical benefit in
      dystrophic, or otherwise swollen, corneas. Of all the toxic responses of the
      endothelium the majority have been identified because of a malfunction of corneal
      thickness regulation, with the resultant corneal swelling, or by morphological
      examination. Only in a few instances has the permeability to non-electrolytes
      (carboxyfluorescein, inulin/dextran) been measured, and even more rarely have ion
      fluxes, or pump activity (3H-ouabain binding), been measured.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1364328
TI  - Retinoids and their nuclear receptors.
AB  - Retinoids (retinoic acid and its biofunctional analogs) are widely involved in
      the control of cell proliferation, cell differentiation, and embryogenic
      development. A series of novel synthetic retinoids (called retinobenzoic acids),
      which include retinoid antagonists, have been developed and have been shown to be
      useful tools to investigate retinoidal action molecular mechanisms. Retinoids
      elicit their biological effects by binding to specific nuclear receptors (RARs)
      belonging to a steroid/thyroid nuclear receptor superfamily. RARs act as retinoid
      dependent transcription factors which bind to a specific gene site and control
      the gene's expression. The diversity of retinoidal actions can possibly be
      interpreted by considering the following characteristics, all of which are quite
      diversified: the structure and spatial/temporal distribution of RARs, the base
      sequences which interact with RARs, the cell type specifically determined
      hierarchy of gene expression, and the nuclear coregulators which interact with
      RARs. Abnormality of an RAR gene which might cause acute promyelocytic leukemia
      is also discussed.

PMID- 1364329
TI  - The effects of ovomacroglobulin on gingival wound healing in rats.
AB  - The effects of ovomacroglobulin (OMG), an alpha 2-macroglobulin-like protease
      inhibitor, were tested on periodontal surgical would healing in 60 Wistar rats.
      The animals were divided into two groups, one receiving topical application of
      0.1% wt/wt OMG ointment and the other receiving ointment base (base). Rats were
      killed at one, three and seven days after surgery for histological and
      immunohistochemical observation. Compared with base group samples, OMG samples
      displayed enhanced capillary formation on anti-laminin-stained sections from day
      3 specimens and a greater quantity of collagen fibers on Azan-Mallory-stained
      sections from day-7 specimens. Results were quantified using an automatic
      computerized pixel image analyzer. Hematoxylin-eosin-stained sections revealed
      that the length of regenerated junctional epithelium was shorter in the OMG group
      than in the base group. The data indicate that the application of OMG to surgical
      wounds accelerated fibroblast growth, collagen deposition, and capillary
      formation in granulation tissue. Thus, OMG could be a useful healing promoter for
      flap surgery.

PMID- 1364330
TI  - Familial gingival hyperplasia: a case of pseudo-Laband syndrome.
AB  - Three siblings with familial gingival hyperplasia and abnormal feet are reported.
      Despite the resemblance to the Laband syndrome, where there are anomalies of the
      terminal phalanges, the abnormalities of the feet in these children were caused
      by the persistent wearing of "flip-flop" sandals. Care is required in the conduct
      of history and examination.

PMID- 1364331
TI  - A preliminary study on the use of a combination of tetracycline and metronidazole
      in the treatment of refractory periodontitis.

PMID- 1364332
TI  - Alteration of root surface morphology by topical application of doxycycline
      hydrochloride on periodontally diseased human teeth.
AB  - The objective of this study was to describe the surface morphology of
      periodontally involved root cementum and its alteration following topically
      applied doxycycline hydrochloride to root-planed and non-planed samples. Root
      surfaces were treated with 100 mg/mL doxycycline hydrochloride solution for three
      minutes. A control group was treated with sterile saline. Observations made by
      scanning electron microscopy showed that treating the periodontally diseased
      cementum surfaces altered the surface topography significantly. Root planed,
      doxycycline-treated surfaces showed characteristics similar to those reported for
      citric acid conditioning. An important finding of the study was that the topical
      application of doxycycline hydrochloride also removed and/or altered the surface
      integument on non-planed root surfaces.

PMID- 1364333
TI  - [Carcinogenic risk assessment of chemicals].
AB  - Assessment of human cancer risk associated with any particular specified chemical
      exposure required a complicated scientific procedure, starting with careful
      review of all pertinent information on the chemical, derived from experimental,
      epidemiological and clinical studies. It is generally agreed within the
      scientific community that there are four steps or components which are typically
      involved in carcinogenic risk assessment. The first step, which is referred to as
      hazard identification, entails a qualitative evaluation of data concerning the
      potential of the chemical to produce a carcinogenic effect in man. The second
      step, exposure assessment, is the process of measuring or estimating real or
      hypothetical human exposure to the chemical of interest. The third step, dose
      response assessment, is the evaluation of both hazard and exposure information to
      estimate the mathematical probability that the carcinogenic potential associated
      with the agent in the human population under defined conditions of exposure. In
      the final step, referred to as risk characterization, all relevant information
      from the first three steps is integrated to characterize the carcinogenic risk
      associated with expected human exposure to the chemical of interest. The process
      of carcinogenic risk assessment, therefore, relies strongly upon the availability
      and quality of information on the chemical of interest. In conclusion, risk
      assessment is defined as a scientific procedure or logical frame-work to assess
      or infer the risk level of risk profile of the agent of interest in man on the
      basis of existing information. The execution of any given risk assessment,
      however, may be hampered by involvement of various uncertainties resulting from
      deficiencies or critical gaps in the necessary information on the chemical. On
      such occasions, it is necessary to make assumptions on the basis of the
      prevailing scientific thought concerning carcinogenic process, to take account of
      these uncertainties, so that risk assessment can still be completed. Therefore,
      risk assessment is regarded as a complex mixture of currently available data on
      the chemical of interest (Specific Information) and assumptions or inference
      rules based on the prevailing scientific thought on chemical carcinogenesis
      (General Information). From these points of view, the common ground for risk
      assessment can be divided into two categories. The first one is the issue of the
      specific information necessary for assessment, which includes the methodology of
      data production and the system of data distribution.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1364334
TI  - [Studies on a modified plasma spray LC/MS device].
AB  - A probe device for LC/MS interface for a sector type mass spectrometer by VG
      Analytical Ltd. is described. The probe capillary for introduction of LC eluent
      to the ion source has a coaxial structure, ie. outer and inner capillary. The
      outer capillary is made of stainless steel to heat the probe, while the inner
      fused silica capillary has the role of insulating the eluent from the high
      voltage of the ion source. This prevents the eluent from excess electric charge
      which causes discharge of ions and disturbs MS experiments. The device also
      contributes to easy management and quick diagnosis as the structure of the probe
      is simple compared to the original and the duplicate structure of the capillaries
      make it possible to examine the probe facilities without taking off the interface
      from the ion source. The cleaning of the probe is also easily accomplished by the
      use of another fused silica capillary.

PMID- 1364335
TI  - [Studies on chemical analysis of mycotoxin (XXI). A rapid analytical method for
      aflatoxins by immunoaffinity column chromatography and high performance liquid
      chromatography].
AB  - An analytical method for aflatoxins using solvent extraction, affinity column
      (containing monoclonal antibodies against aflatoxins bound onto agarose) clean-up
      and high performance liquid chromatographic determination was applied to the
      analysis of aflatoxins in peanuts, pistachio nuts, white and black peppers and
      corn. Recoveries of aflatoxins B1, B2, G1 and G2 spiked to peanuts, pistachio
      nuts and corn at the level of 20 ppb were 77.4-81.4, 70.1-77.9 and 72.3-94.8%,
      respectively. In the case of white and black peppers, because the spiked
      aflatoxin recovery rate was low, further purification steps should be studied.
      The stability of the affinity column was good. This procedure is recommended as a
      rapid and reliable method for the analysis of aflatoxins in the three kinds of
      foods, peanuts, pistachio nuts and corn.

PMID- 1364336
TI  - [Determination of butylated hydroxy-anisole in oily foods by high-performance
      liquid chromatography with fluorescence detection].
AB  - Simple and rapid determination method for butylated hydroxyanisole [2(3)-tert
      butyl-4-hydroxyanisole)] (BHA) (CAS no. 25013-16-5) is developed. BHA was
      extracted from oily foods with hexane and from hexane layer to acetonitrile. The
      acetonitrile layer was either directly or after concentration injected to high
      performance liquid chromatograph (HPLC) equipped with a fluorescence detector. As
      the internal standard for determination, tert-butyl-p-cresol was used. The
      conditions for HPLC were as follows. Column; Shim-pack CLC-ODS (6 mm i.d. x 15
      cm): Mobile phase; 75% methanol: Excitation wave length for the fluorescence
      detector 298 nm; Emission wave length 332 nm. The recoveries of BHA from salad
      oil, margarine, and butter added 10 micrograms/g or 200 ng/g of BHA were
      satisfactory.

PMID- 1364337
TI  - [Measurement of prostaglandin E2 content in lung tissue of mouse].
AB  - A radioimmunoassay (RIA) was applied for the determination of PGE2 levels in the
      lung from 4 groups of male ICR mice 1) fed a standard diet, 2) fed a 20% corn oil
      supplemented diet (HFD) for 2 weeks, 3) given a single s.c. injection of 15 mg/kg
      of 4NQO, a potent lung carcinogen and 4) given a s.c. injection of 4NQO and
      subsequently fed HFD for 2 weeks. Animals were sacrificed at week 3, and the lung
      was carefully excised and frozen in liquid nitrogen to prevent the postmortem
      synthesis of PGE2. PGE2, extracted from the lung tissue, was purified and then
      measured with or without adding a known amount of PGE2. The lung levels of PGE2
      were shown to be significantly higher in the groups treated with HFD and/or 4NQO
      than the group fed a standard diet. These results show that the modified RIA
      method can be used for the measurement of PGE2 contents in the tissue of animals.

PMID- 1364338
TI  - [Studies on activated charcoal concerning the determination of sulfate in food
      coal-tar dyes].
AB  - It is very difficult to determine the content of sulfate in food coal-tar dye by
      the method designated in the "Japanese Standards of Food Additives(V)", because
      the endpoint on titration is difficult to gauge. We determined the concentration
      of sulfate in food dye nephelometrically after decolorization with charcoal but
      obtain different values depending on the kind of charcoal used. Because the
      adsorbed or eluted sulfate in the various charcoals were dispersed widely, so we
      tested the sulfate contents in five kinds of charcoals. It was found that all
      kinds of charcoals eluted or adsorbed sulfate in varying degrees. Therefore no
      charcoal was found to be satisfactory for use in the sulfate test.

PMID- 1364339
TI  - [Studies on the identification of psychotropic substances (VII). Preparation and
      various analytical data of standard references of some hallucinogens, 3,4
      methylenedioxyamphetamine (MDA), 3,4- methylenedioxymethamphetamine (MDMA) and 5
      methoxy-3,4- methylenedioxyamphetamine (MMDA)].
AB  - The Reference Standards of 3, 4-methylenedioxyamphetamine (MDA), 3, 4
      methylenedioxymethamphetamine (MDMA) and 5-methoxy-3,4-methylenedioxyamphetamine
      (MMDA) were prepared. Their purities determined by HPLC were 99.8% for DMA
      hydrochloride, 99.8% for MDMA hydrochloride and 99.5% for MMDA hydrochloride. For
      the identification and determination, various analytical data of the three drugs
      were measured and studied by TLC, UV, IR, HPLC, GC/MS and NMR.

PMID- 1364340
TI  - [DNA damage test in forestomach squamous epithelium of F344 rat following oral
      administration of ethyl acrylate].
AB  - The alkaline elution assay were applied for testing DNA damage of forestomach
      squamous epithelium in male F344 rat after oral administration of ethyl acrylate
      (EA), a forestomach carcinogen. The animals were starved for 18 hr and then given
      a single oral dose of EA. No DNA damage were observed by EA at the concentration
      of 0.1-4.0%. The weights of the forestomach increased with EA dose, reflecting
      edema and inflammation, but that of glandular stomach did not change with its
      dose.

PMID- 1364341
TI  - [Preliminary screening for antiviral AIDS drugs. I. Report on fiscal year 1988].
AB  - Preliminary screening for antiviral AIDS drugs has been carried out, using three
      different in vitro assay systems. Among 105 samples tested, 13 were found to
      inhibit the growth of HIV in vitro. Eleven of 13 were well-known anti-HIV
      chemicals, while the remaining two of plant origin were new chemicals whose anti
      HIV activities have not been reported elsewhere.

PMID- 1364342
TI  - [Study on essential metal concentration in the organs of rats (report 1)].
AB  - Concentration of 5 elements (Ca, Cu, Fe, Mg, Zn) in 10 organs (brain, heart,
      lung, liver, kidney, spleen, testis, thymus, salivary gland and bone) and serum
      of rats were determined by inductively-coupled argon plasma atomic emission
      spectrometry (ICP). Samples were digested with nitric acid and perchloric acid in
      a sealed double Teflon vessel with polypropylene jacket by heating with a
      microwave oven. The concentration of 5 elements in the organs can be grouped into
      5 categories as follows. (1) heart, liver and spleen (Mg > Fe > Ca > Zn > Cu) (2)
      lung and kidney (Mg > Ca > Fe > Zn > Cu) (3) brain, thymus and testis (Mg > Ca >
      Fe = Zn > Cu) (4) serum and bone (Ca > Mg > Fe = Zn > Cu) (5) salivary gland (Ca
      = Mg > Fe > Zn > Cu).

PMID- 1364343
TI  - [Thiamine Hydrochloride Reference Standard (Control 891) of National Institute of
      Hygienic Sciences].
AB  - The raw material of thiamine hydrochloride was examined for preparation of the
      "Thiamine Hydrochloride Reference Standard". Analytical results were as follows:
      melting point 242.7 degrees; pH 3.2 (1 g, water, 100 ml); IR spectrum the same as
      that of JP Reference Standard (Control: 841); one and two impurities detected by
      TLC and by HPLC analyses, respectively; assay by thiochrome method 100.3% and by
      HPLC 100.1% against the JP Reference Standard. Based on the results, the present
      raw material was authorized to be the Reference Standard of the National
      Institute of Hygienic Sciences.

PMID- 1364344
TI  - [Mestranol Reference Standard (Control 881) of National Institute of Hygienic
      Sciences].
AB  - The raw material of mestranol was examined for preparation of the "Mestranol
      Reference Standard". Analytical results for the sample were as follows: UV
      spectrum indicated absorption maxima at 279 and 287 nm and absorptivity at 279 nm
      E1%1cm 66; IR spectrum indicated specific absorption at 1612, 1578, 1505, 1253,
      and 1060 cm-1; optical rotation +3.9 degrees; melting point 153.1 degrees; loss
      on drying 0.03%; TLC and HPLC analyses indicated one impurity, respectively; the
      purity was assumed to be 99.3% by HPLC analysis. Based on the results, the
      present raw material was authorized to be the Reference Standard of the National
      Institute of Hygienic Sciences.

PMID- 1364345
TI  - [Betamethasone Sodium Phosphate Reference Standard (Control 881) of National
      Institute of Hygienic Sciences].
AB  - The raw material of betamethasone sodium phosphate was examined for preparation
      of the "Betamethasone Sodium Phosphate Reference Standard". Analytical results
      for the sample were as follows: pH 7.90; optical rotation + 100.5 degrees; IR
      spectrum the same as USP Reference Standard of Betamethasone Sodium Phosphate;
      TLC indicated no impurities, but 5 kinds of impurities were detected in small
      amounts by HPLC; water content 14.7%; assay 100.2% by HPLC. Based on the above
      results, this raw material was authorized to be the Reference Standard of the
      National Institute of Hygienic Sciences.

PMID- 1364346
TI  - [Dexamethasone Sodium Phosphate Reference Standard (Control 891) of National
      Institute of Hygienic Sciences].
AB  - The raw material of dexamethasone sodium phosphate was examined for preparation
      of the "Dexamethasone Sodium Phosphate Reference Standard". Analytical results
      were as follows: UV spectrum indicates absorption maxima at 242 nm and
      absorptivity at 242 nm is E1%1cm 304; optical rotation +79.0%; pH 7.7; ethanol
      5.2%; water 6.0%; HPLC analysis indicates small amounts of three impurities and
      the purity was assumed to be 99.8%; assay by HPLC indicated 100.9% against the
      USP Reference Standard of "Dexamethasone Phosphate". Based on the results, the
      present raw material was authorized to be the Reference Standard of the National
      Institute of Hygienic Sciences.

PMID- 1364347
TI  - [Hydrocortisone Acetate Reference Standard (Control 891) of National Institute of
      Hygienic Sciences].
AB  - The raw material of hydrocortisone acetate was examined for preparation of the
      "Hydrocortisone Acetate Reference Standard". Analytical results were as follows:
      E1%1cm (242 nm) 403; IR spectrum indicates specific absorption at 3424, 1745,
      1721, 1630, and 1374 cm-1; optical rotation +164.4 degrees (in dioxane); melting
      point 219.5 degrees (decomposition); loss on drying 0.16%; TLC and HPLC analyses
      indicated one and three impurities, respectively; assay by HPLC was 99.7% against
      the previous Reference Standard. Based on the results, the present raw material
      was authorized to be the Reference Standard of the National Institute of Hygienic
      Sciences.

PMID- 1364348
TI  - [Hydrocortisone Sodium Phosphate Reference Standard (Control 891) of National
      Institute of Hygienic Sciences].
AB  - The raw material of hydrocortisone sodium phosphate was examined for the
      preparation of the "Hydrocortisone Sodium Phosphate Reference Standard".
      Analytical data obtained were as follows: pH, 8.2; optical rotation [alpha]D20,
      +124.1 degrees; Infrared spectrum, same as that of BP Reference Standard of
      Hydrocortisone Sodium Phosphate; thin-layer chromatography, no impurities were
      detected; high-performance liquid chromatography (HPLC), 2 kinds of small amount
      of impurities were detected; assay, 99.2% by the enzyme method and 99.9% by the
      HPLC method in terms of the BP Reference Standard. Based on the above results,
      this raw material was authorized to be the Reference Standard of the National
      Institute of Hygienic Sciences.

PMID- 1364349
TI  - [Prednisolone Sodium Phosphate Reference Standard (Control 891) of National
      Institute of Hygienic Sciences].
AB  - The raw material of prednisolone sodium phosphate was examined for preparation of
      the "Prednizolone Sodium Phosphate Reference Standard". Analytical data obtained
      were as follows: pH 7.6; optical rotation [alpha]D25, +99.0 degrees; Infrared
      spectrum, same as that of BP Reference Standard; Thin-layer chromatography, 4
      impurities were detected; high-performance liquid chromatography (HPLC), 7 kinds
      of impurities were detected; residual solvent, 0.76% (ethnol) and 0.23% (hexane);
      assay, 100.2% by the enzyme method and 99.7% by the HPLC method in terms of the
      BP Reference Standard. Based on the above results, this raw material was
      authorized to be the Reference Standard of the National Institute of Hygienic
      Sciences.

PMID- 1364350
TI  - [Tocopherol Succinate Reference Standard (Control 881) of National Institute of
      Hygienic Sciences].
AB  - Tocopherol succinate was tested for the preparation of "Tocopherol Succinate
      Reference Standard (Control 881)". Analytical data obtained were as follows:
      infrared spectrum, same as Tocopherol Succinate Reference Standard (Control 851);
      absorbance, E1cm1% (286 nm) = 40.5; thin-layer chromatography, contaminants were
      not detected until 50 micrograms; high-performance liquid chromatography, three
      contaminants were detected; loss on drying, 0.09%; assay, 100.0%. On the basis of
      the above results, this material was authorized as the Japanese Pharmacopoeia
      Standard (Control 881).

PMID- 1364351
TI  - [Methyldigoxin Reference Standard (Control 881) of National Institute of Hygienic
      Sciences].
AB  - Methyldigoxin was tested for preparation of the "Methyldigoxin Reference Standard
      (Control 881)". Analytical data obtained were as follows: infrared spectrum 3456,
      1738, 1086 cm-1; ultraviolet spectrum lambda max = 219 nm; absorbance E1cm1% (219
      nm) = 193.1; water 0.99%; optical rotation [alpha]546.1(20) = +22.5 degrees; thin
      layer chromatography and high-performance liquid chromatography indicates two
      impurities, respectively; quantitative analysis of acetone 3.87%; assay by
      spectrophotometry 100.3% against Digoxin Reference Standard (Control 802). On the
      basis of the above results, this material was authorized as the National
      Institute of the Hygienic Sciences Reference Standard (Control 881).

PMID- 1364352
TI  - [Cyanocobalamin Reference Standard (Control 891) of National Institute of
      Hygienic Sciences].
AB  - Cyanocobalamin was tested for preparation on the "Cyanocobalamin Reference
      Standard (Control 891)". Analytical data obtained were as follows: loss on
      drying, 9.77%; infrared spectrum, same as that of the Cyanocobalamin Reference
      Standard (Control 871); thin-layer chromatography, five contaminants were
      detected; high-performance liquid chromatography, nine contaminants were
      detected; assay, 100.00% by JP XI method and 99.79% by HPLC method in terms of
      the JP Reference Standard (Control 871), respectively. On the basis of the above
      results, this material was authorized as the Japanese Pharmacopoeia Standard
      (Control 891).

PMID- 1364353
TI  - [National Institute of Hygienic Sciences Standard (the Japanese Pharmacopoeia
      Standard) "Endotoxin Reference Standard" (Control 891)].
AB  - The second "Endotoxin Reference Standard" (Control 891) of the National Hygienic
      Sciences (Japanese Pharmacopoeia Standard) was prepared. As a result of the test
      of its potency against the preceding lot of the Reference Standard (Control 881),
      the second "Endotoxin Reference Standard" (Control 891) containing 16000
      endotoxin units per vial was authorized.

PMID- 1364354
TI  - [On a minor component found in the lysozyme reference standard].
AB  - A minor component separated by HPLC from egg-white lysozyme was found to have a
      different substrate specificity from the main component, lysozyme. However, it
      did not show any difference in molecular weight and immuno-cross reactivity from
      lysozyme. There was no evidence based on our study that this minor component is
      an artificially-produced substance.

PMID- 1364355
TI  - [Studies on the quality of enzyme preparations (XI)--Kallidinogenase
      preparations].
AB  - Qualitative tests of 22 kinds of commercially available kallidinogenase
      preparations were carried out by the enzymological method. These preparations
      consisted of 16 kinds of tablets, 5 kinds of capsules and 1 kind of ampoule. One
      sample of tablet showed kallidinogenase activity less than 80% of the labeled
      amount by spectrophotometry, pH stat and kinin-liberating methods. All other
      preparations were found to have 90-120% 120% of the labeled amount by
      spectrophotometry using S-2266 as the substrate. Other enzymes, i.e. kininase,
      trypsin and chymotrypsin were found as impurities, but the cntants were very low.

PMID- 1364356
TI  - [Gas chromatographic determination of azinphos-methyl in imported crops].
AB  - A gas chromatographic method for the quantitative analysis of azinphos-methyl in
      agricultural products was studied. Azinphos-methyl was extracted with acetone.
      The extract was cleaned up by charcoal column chromatography for the treatment of
      wheat and soybean and by using coagulating reagent for the treatment of lemon and
      orange, then determined by a gas chromatograph equipped with a flame photometric
      detector (FPD). The mean recovery of azinphos-methyl added to wheat, soybean and
      lemon at the level of 0.1 or 0.2 microgram/g was 96.6-101.0%. The detection limit
      of azinphos-methyl was 0.04 microgram/g in the case of wheat and soybean
      extracted from 10 g of each sample and 0.02 microgram/g in the case of lemon and
      orange extracted from 20 g of each sample. Azinphos-methyl was not detected in
      any of the imported, 6 wheat, 6 soybean, 5 lemon and 4 orange tested using the
      above mentioned method.

PMID- 1364357
TI  - Production and characterization of monoclonal and polyclonal antibodies against
      digoxin.
AB  - Three hybridoma cell lines (DIG 64. 2B. 5, DIG 104. H10.1 and DIG 222. 4D. 5)
      producing monoclonal antibodies against digoxin were established, and the
      properties of these monoclonal antibodies were characterized and compared with
      three polyclonal rabbit anti-digoxin antisera. Both polyclonal and monoclonal
      antibodies gave association constants ranging from 10(9) to 10(10) (M-1). The
      monoclonal antibodies were of the IgG1(kappa) or IgG2b(kappa) subclass. Cross
      reactivities of these monoclonal antibodies and polyclonal antisera with various
      related cardenolides and their aglycones were determined by competitive
      radioimmunoassay. The monoclonal antibodies were specific for digoxigenin
      containing glycosides such as lanatoside C and deslanoside, but not for
      digitoxigenin-containing glycosides. On the other hand, the specificities of the
      polyclonal antisera were less strict than the monoclonal antibodies and
      relatively cross-reactive with digitoxin. It was shown that the RIA for digoxin
      using DIG 64. 2B. 5 is sensitive enough to detect 0.2-0.3 nM (30-60 pg/tube) of
      digoxigenin-containing cardenolides.

PMID- 1364358
TI  - [Evaluation of immunotoxicity testings using azathioprine-treated rats: the
      International Collaborative Immunotoxicity Study (Azathioprine)].
AB  - The immunotoxicological effects of azathioprine (AZP) were examined by enhanced
      histopathological and function tests in the rat which is routinely used in
      toxicological tests. Male F344 rats were orally administered AZP in doses of 0,
      2.5, 12.5 and 25.0 mg/kg/day for 28 days. Reductions in the organ weights of the
      thymus, spleen, liver, kidney, and testis in a dose-dependent manner were
      confirmed. Hematological examination revealed a marked decrease in the number of
      WBCs, which was associated with a decrease in the number of lymphocytes. In the
      femoral bone marrow, a significant reduction in the total cell number attributed
      to the decrease in the number of lymphocytes and granulocytes was observed.
      Histopathologically, atrophy and obfuscation of the corticomedullary junction in
      the thymus, the decrease of lymphocytes in the thymus and spleen, and the
      disappearance of germinal centers in the lymph nodes were observed. As for the
      functional testings, azathioprine treatment did not affect remarkably the PFC
      number and the NK cell activity per unit spleen cell number. However, the total
      spleen cell number per spleen was decreased in a dose-dependent manner.
      Therefore, the total functional activities (PFC and NK) per spleen were
      decreased. Thus, in the AZP-treated F344 rats, it was shown that the enhanced
      histopathological tests were useful to evaluate potential risks to the immune
      system.

PMID- 1364359
TI  - [Future development of the Japanese chemicals regulation data search system and
      the effective use of the IRPTC legal file].
AB  - After ten years of international cooperation in developing the IRPTC Legal File,
      its usefulness in searching for chemicals regulation data from abroad and in
      Japan was studied. The superiority of the database in offering summaries of the
      legal texts from 50 countries and 7 international organizations was obvious, but
      the need for improvements in the coverage and the accuracy of the data was found.
      The development of a Japanese database of legal information on chemicals based on
      international information exchange is desirable.

PMID- 1364360
TI  - [Twenty-eight-day repeated dose toxicity test for tetrachlorvinphos in Wistar
      rat].
AB  - A 28-day oral toxicity test of tetrachlorvinphos (TCV) was conducted in male and
      female Slc: Wistar rats by gavage at dose levels of 0, 10, 100 or 1000 mg/kg/day.
      The male and female rats showed dose-related inhibition of serum cholinesterase
      activity and erythrocyte acetylcholinesterase activity. At a dose of 1000 mg/kg,
      body weight gain was decreased in males, and there were 6 deaths in females.
      Adrenal gland, liver, kidney and thyroid gland weights were increased. The
      adrenal lesions were characterized by vacuolization and swelling of the cortex
      cells. The hepatic lesions consisted of vacuolization and necrosis of the
      hepatocytes. The renal lesions consisted of regeneration and necrosis of the
      tubular epithelial cells. These lesions were mostly observed at a dose of 1000
      mg/kg. After a 14-day recovery period in the 1000 mg/kg group, the changes of
      cholinesterase, total cholesterol, gamma-glutamyltransferase, alkaline
      phosphatase, aspartate aminotransferase and blood urea nitrogen in serum were
      restored or showed a tendency toward recovery. However, the lesions in the kidney
      and adrenal remained. More than 14 days are therefore considered to be needed for
      recovery. At doses of more than 10 mg/kg, significant inhibition of the serum
      cholinesterase activity in both sexes, erythrocyte acetylcholinesterase activity
      in males, and lesions of the adrenal gland in females were observed. Target
      organs for TCV-treated rats were the adrenal, liver and kidney. It was concluded
      that the NOEL under this experimental condition is less than 10 mg/kg/day.

PMID- 1364361
TI  - [Studies on the teratogenic potential of 2,2'-methylenebis (4-methyl-6-tert
      butylphenol) in rats].
AB  - 2,2'-Methylenebis (4-methyl-6-tert-butylphenol), an antioxidant, was given orally
      to pregnant Wistar rats by stomach intubation at the dose levels of 93.5, 187 or
      375 mg/kg body weight during days 7 to 17 of pregnancy, and the effects of the
      compound on dams and fetal developments were examined. In the dams at the two
      higher doses of 187 and 375 mg/kg, toxic signs such as hair fluffing and
      diarrhoea were observed, and their body weight gain and food consumption were
      suppressed. Two dams, which showed marked diarrhoea in the highest dose group,
      died. However, there was no evidence of fetal malformation attributable to
      treatment with the compound in any of the dose groups treated, although a slight
      increase in fetal death was found in the highest dose group. It is concluded that
      2,2'-methylenebis (4-methyl-6-tert-butylphenol) has a weak lethal effect on fetal
      development but not a teratogenic effect in the rat.

PMID- 1364362
TI  - [Effects of crude soybean trypsin inhibitor on pancreatic atrophy induced by BOP
      treatment in hamsters].
AB  - Experiment I: Female Syrian golden hamsters were given 5 weekly sc injections of
      N-nitrosobis (2-oxopropyl)amine (BOP) while simultaneously being treated with
      SBTI diet for 5 weeks (BOP+ SBTI). Other two groups were treated with BOP or SBTI
      alone. Sacrificed at week 30, the numbers of both adenocarcinomas and dysplastic
      lesions were decreased in the BOP+SBTI group relative to the BOP alone group.
      Experiment II: Female hamsters were given 3 weekly sc injections of BOP and then
      fed a SBTI diet for 40 weeks. The numbers of dysplastic lesions was decreased in
      the BOP and SBTI group relative to the BOP alone group. An inhibitory effect was
      observed for the pancreas in hamsters fed SBTI after BOP treatment. In
      experiments I and II, atrophic changes of pancreatic exocrine tissues and fatty
      tissue infiltration were observed in hamsters treated with BOP. The ratios of
      exocrine atrophy in pancreas sections were measured with the aid of an image
      processor. Areas (2.4 mm2) of splenic and gastric lobes were selected randomly,
      and the included exocrine tissue measured to allow calculation of percentage area
      of exocrine tissue atrophy. In hamsters simultaneously treated with BOP and SBTI,
      the percent areas of intact exocrine tissues in both splenic and gastric lobes
      were significantly higher (87% and 83%) as compared to the BOP group values (61%
      and 61%), at the level of p < 0.01, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1364363
TI  - [Early histopathological changes in trachea, bronchus and lung, and changes in
      lipid peroxidation in hamsters, due to inhaled cigarette smoke].
AB  - The main objective of this work was to determine the influence of cigarette smoke
      exposure on the mechanisms which promote respiratory tumors. And another aim was
      the accumulation of basic data regarding the effect of cigarette smoke exposure
      in hamsters in the Hamburg II smoking machine. Male Syrian golden hamsters were
      caused to inhale cigarette smoke in the Hamburg II smoking machine. The hamsters
      inhaled cigarette smoke twice a day, for 9 minutes, 5 times a week. The
      administration period were 1,2,4,8 and 12 weeks. For each inhalation, the
      rotating disk was fitted with 30 cigarettes. Each puff, 35 ml in volume, was
      diluted seven times with room air. At the completion of administration, subjects
      were examined histopathologically, and lung and serum lipid peroxidation levels
      were also measured. Histopathological examination of the respiratory tract and
      alveolar epithelium disclosed no cigarette smoke-related hyperplastic lesion in
      any animal. And in the hamsters which inhaled cigarette smoke, "smoke cells"
      accumulation were observed in the alveolar space after 8 and 12 weeks exposure.
      Significant increase in the number of BrdU positive cells were not observed
      following cigarette smoke exposure, but a tendency for lung malondialdehyde (MDA)
      levels to increase was evident. On the other hand, serum lipid peroxide (LPO)
      levels showed a marked decrease in the animals exposed to cigarette smoke for 2,4
      and 8 weeks in comparison with the identically handled control animals. But serum
      LPO levels showed a tendency to increase with cigarette smoking during all
      experimental periods. The above results suggested that cigarette smoking may
      cause a change in lipid peroxidation levels such as lung MDA and serum LPO
      levels.

PMID- 1364364
TI  - [Ultrastructural localization of myelin bodies and acid phosphatase activities in
      the liver and kidney induced by quinacrine in rats].
AB  - Electron microscopic studies were conducted to reveal the ultrastructural aspects
      of the myelin body and acid phosphatase activity in rats induced by quinacrine,
      an antimalarial drug. Each of 22 rats in three groups were examined. The first
      group of control rats was initially given a single i.p. dose (200 mg/kg) of
      diethylnitrosamine (DEN) only and then fed a CRF-1 basal diet for 8 weeks. The
      second and third group were treated with DEN or saline, and starting 2 weeks
      later, were fed a CRF-1 basal diet supplemented with 500 ppm quinacrine for 6
      weeks. All animals were subjected to a partial hepatectomy at week 3, and then
      sacrificed at week 8. Liver and kidney tissues specimens from 2 rats per group
      were collected for routine electron microscopic study. Furthermore, the activity
      of acid phosphatase, a key enzyme for lysosomal activity, was also investigated.
      In this study, tissues were fixed with a solution of 2.5% glutaraldehyde in 0.1 M
      sodium cacodylate buffer. After fixation, tissues were frozen and their 8 microns
      sections were treated with Gomori's lead nitrate buffer solution, and post-fixed
      with a 1% osmium solution. After being embedded in Epon 812, ultrathin sections
      were made. Intracellular myelin bodies were observed in the hepatocytes,
      interlobular bile duct cells, renal glomerular podocytes and renal tubular cells
      in the quinacrine treated groups, but not were observed in rats treated with DEN
      alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364365
TI  - [Twenty-eight day repeated dose toxicity test of dicyclopentadiene in F344 rat].
AB  - A twenty-eight day repeated dose toxicity test of dicyclopentadiene (DCPD) was
      carried out in male and female F344 rats at the dose levels of 200, 40, 8 or 0
      mg/kg/day. Thirty six animals of both sexes were divided into 6 groups of equal
      number. All groups were treated i.g. administration for 28 days daily, and two
      groups of them, at the dose levels of 200 and 0 mg/kg, were used for
      investigation of recovery. Inhibition of body weight gain was observed in the 200
      mg/kg groups in both sexes and the 40 mg/kg group in male, but in female this
      inhibition was recovered at day 17 of the treatment. Increases in liver and
      adrenal gland weights, and decrease in thymus weight were noted in the 200 mg/kg
      groups in both sexes, and increase in kidney weight was also observed in the 200
      and 40 mg/kg groups in male. On histopathological examination, hypertrophy of the
      adrenal cortex, and foamy cytoplasm in hepatocytes were observed in the 200 mg/kg
      groups of both sexes. Repair of histopathological lesions occurred within 14 days
      resting period. Based on these findings, it was concluded that the No Observed
      Effect Level of DCPD would be 8 mg/kg/day.

PMID- 1364366
TI  - [Subchronic oral toxicity study of tannic acid in F344 rats].
AB  - A 13-week subchronic oral toxicity study of tannic acid (TA) was carried out in
      F344 rats at dose levels of 0, 0.025, 0.05, 0.1, 0.2 and 0.4% in the drinking
      water, to determine appropriate dose levels for a subsequent 2-year
      carcinogenicity study. The rats were randomly allocated to 6 groups, each
      consisting of 12 males and 12 females. No animals died during the administration
      period. There were no significant difference in body weight gain, food
      consumption and organ weights between the treated and control groups, although a
      slight decrease in water intake was seen in the 0.4% TA treated group. No
      specific changes were observed in any parameters in the hematological and
      biochemical investigations. Histopathological examination, revealed toxic changes
      in the TA treated male groups, in the form of necrosis in the liver, but
      toxicologically it was of minor importance. From these results, it was concluded
      that the provable maximum tolerable dose of TA in the drinking water would be
      more than 0.4%. In consideration of the avoidance of drinking water, the maximum
      tolerable dose of tannic acid was determined to be 0.5%, when given in the
      drinking water.

PMID- 1364367
TI  - [Toxicity and carcinogenicity studies of musk xylol in B6C3F1 mouse].
AB  - Toxicity and carcinogenicity studies of musk xylol were examined in B6C3F1 mice.
      The LD50 of the chemical was considered to be more than 4000 mg/kg. In the acute
      toxicity and 14-day repeated-dose oral toxicity studies, tremor was observed in
      some animals given high doses of the chemical. In the 17-week repeated-dose oral
      toxicity study, musk xylol was given at dietary dose levels of 0.0375, 0.6%.
      During the experimental period, almost all mice given 0.3% or more died. There
      was no difference in the body-weight gain between the treated groups given 0.15%
      or less and the control group. Histologically, enlargement and irregularity of
      hepatocyte were found in both sexes given 0.15% or more. Based on the results,
      the chemical was given at dietary levels of 0 (control), 0.075 or 0.15% for 80
      weeks in the carcinogenicity study. Overall tumor incidences in all treated
      groups of both sexes were significantly higher than those in the respective
      controls. Combined malignant and benign liver cell tumors increased clearly in
      both sexes and a significant positive trend for the occurrence of hepatocellular
      carcinomas was noted in males. Incidences of lung and Harderian gland tumors and
      lymphomas in treated groups were also slightly higher than those in controls. In
      addition, incidences and total numbers of malignant tumors increased
      significantly in treated groups of both sexes, although no dose-relation was
      evident. The results demonstrated that musk xylol is carcinogenic in B6C3F1 mice
      of both sexes when given at dose-levels of 0.075 or 0.15% in the diet for 80
      weeks.

PMID- 1364368
TI  - [Usage of chitosan as a pharmaceutical material effectiveness as an additional
      additives of sodium alginate].
AB  - Application of chitosan, a deacetylated compound of chitin obtained from shells
      of shrimps, was investigated with reference to the pharmaceutical excipient for
      directly compressed tablets. Several drugs were chosen as model compounds and
      their in vitro dissolution tests were carried out according to the JP XI
      dissolution test. When chitosan was used alone as an excipient, immediate-release
      tablets were obtained, as already reported. But when more than 5% of sodium
      alginate, 1000 cps, was added as excipient, tablets showed an extended-release
      property under the present experimental conditions.

PMID- 1364369
TI  - [Identification of nutmeg by thin-layer chromatography and its introduction to
      Japanese standards for non-pharmacopoeial crude drugs].
AB  - When nutmeg was extracted with hot methanol and cooled, much precipitate was
      produced. The colorless crystals, obtained on recrystallization, were identified
      as trimyristin by spectroscopic means and by direct comparison with the standard.
      Then, the identification of nutmeg was established by using the same extraction
      as above and subjecting the precipitate to thin-layer chromatography. This method
      was newly introduced to the Standards for Non-pharmacopoeial Crude Drugs.

PMID- 1364370
TI  - [Recent world-wide advances in irradiation of food and its identification].
AB  - Irradiation (ionizing radiation) of various foods is growing in popularity
      internationally. For example, it is used as a substitute for the use of post
      harvest pesticides. This trend has served to intensity research on the
      identification of irradiated foods. The first Research Co-ordinated Meeting on
      Analytical Detection Method for Irradiated Foods was held in Poland under the
      sponsorship of FAO/IAEA in 1990 in order to solve problems related to the
      international trade of irradiated foods and to ensure their correct labelling in
      the market. In this review, the world-wide advances in the irradiation of food
      and its identification are introduced and discussed.

PMID- 1364371
TI  - [Determination of thiabendazole (TBZ) in grapefruit].
AB  - The officially recognized gas chromatographic method (detector: nitrogen
      phosphorus detector) for determination of thiabendazole (TBZ) in grapefruits,
      tends to give results that are higher than the actual values. This may be due to
      the fact that more of the TBZ in authentic TBZ solution is adsorbed on the column
      than TBZ in the sample solutions that contain a lot of impurities. Because of
      this difficulty, two liquid chromatographic methods were compared. If a
      fluorescence detector is available, the method of Nakazato et al. (ethyl acetate
      extraction and ion pair HPLC) is the best for preparation of test solution. When
      an ultraviolet detector is used, clean-up of the ethyl acetate extract is
      necessary. By the method of Kitada et al., the retention time of TBZ becomes
      shorter after injection of many samples. In view of these results, the method of
      Nakazato et al. is the methods-of-choice for TBZ in grapefruit.

PMID- 1364372
TI  - Migration and material tests of some food-contact plastic wares made in Thailand.
AB  - Migration and material tests of food-contact plastic wares were carried out in
      compliance with the Thai Food Act. Sample materials studied were melamine resin,
      polyethylene, polypropylene, polystyrene, and polyvinyl chloride. Migration
      levels of phenol, formaldehyde, colors and heavy metals were determined. A test
      for vinyl chloride monomer in polyvinyl chloride was carried out. Migrant and
      residual levels in all samples were in compliance with the Act.

PMID- 1364373
TI  - [Preliminary screening for antiviral AIDS drugs. II. Report on fiscal year 1989].
AB  - Preliminary screening for antiviral AIDS drugs was carried out using three
      different in vitro assay systems. Among 104 samples tested, six were found to
      inhibit the growth of HIV in vitro. Four of six were acidic polysaccharides of
      sea weed origin and one was a well-known anti HIV chemical whose anti-HIV
      activity has not been reported.

PMID- 1364374
TI  - [A study on toxicological information search--an example from a study on food
      additives].
AB  - The information search method for toxicological evaluation of food additives was
      examined. Both a survey of the existence of critical reviews or specific
      databases for toxicological evaluation and the performance of preliminary online
      search are important for a comprehensive and effective search. Examples of file
      selection and search scheme examination are reported. The results are considered
      to be generally applicable to toxicological information search for other groups
      of chemicals.

PMID- 1364375
TI  - [Summaries on the first draft of the EHC monographs in 1990].
AB  - The first drafts of the EHC monographs in 1990 were summarized into Japanese. The
      chemicals consist of hexachlorocyclopentadiene, trichlorfon, fenitrothion,
      methylparathion, trichloroethane, platinum and selected platinum salts, di(2
      ethylhexyl)phthalate, partially halogenated chlorofluorocarbons, methyl ethyl
      ketone, and propachlor.

PMID- 1364376
TI  - [Enhancing effect of L-histidine on the formation of 8-hydroxy-deoxyguanosine
      induced by hydrogen peroxide in vitro].
AB  - Treatment of deoxyguanosine with H2O2 (56 mM) at 37 degrees C for 2 hrs resulted
      in the formation of 8-hydroxydeoxyguanosine (8-OH-dG). The formation of 8-OH-dG
      by H2O2 was increased about 3-folds in the presence of 78 microM L-histidine (L
      His). The result suggests that oxidative DNA damage induced by H2O2 in vitro
      might be enhanced by L-His.

PMID- 1364377
TI  - [Study on essential metal concentration in the organs of rats (report 2)-
      lung.liver.kidney.spleen].
AB  - The objective of this study was to obtain the normal ranges of essential metals
      in male and female Slc: Wister rats aged 9 or 11 weeks. Concentration of 10
      elements (Ca, Cu, Fe, K, Mg, Mn, Na, P, S and Zn) in the lung, liver, kidney and
      spleen of rats was determined by inductively coupled argon plasma atomic emission
      spectrometry (ICP). Each sample was digested with nitric acid and perchloric acid
      in a sealed double Teflon vessel with polypropylene jacket by heating with a
      microwave oven. The concentrations of Fe and Mn in the liver were different
      between males and females. The Fe level in the female was higher than that in the
      male, and Mn level in male was higher than that in female. The concentration of
      Fe in the spleen was different by sex and ago. The Fe level in female was 2.3
      times higher than that in male, and that in rats of 11 weeks was 1.8 times higher
      than that of 9 weeks.

PMID- 1364378
TI  - [A study on the usefulness of the OECD Combined Repeat Dose and
      Reproductive/Developmental Toxicity Screening Test (ReproTox)].
AB  - We studied the usefulness of the OECD combined Repeat Dose and
      Reproductive/Developmental Toxicity Screening Test (ReproTox) using
      cyclophosphamide (CP), which is well known for its toxicological properties. CP
      was given daily by gavage to groups of 12 male and 12 female 8-week-old Sprague
      Dawley rats at doses of 0, 2, 3, 4.5 or 6.7 mg/kg. Significant decreases in body
      weight and food consumption were observed in males given 6.7 mg/kg and in all
      treated females. One, 3 and 12 females died during pregnancy in the groups given
      3, 4.5 and 6.7 mg/kg, respectively. In males 2 died in the 6.7 mg/kg group.
      Leukopenia and anemia were evident in treated males. The thymus and spleen
      weights were significantly decreased in treated rats. Histopathologically,
      atrophy of the thymus, spleen and bone marrow was observed. With respect to the
      reproductive/developmental toxicity, dose-dependent increases in postimplantation
      loss and postnatal death of pups were found in treated dams. The body weight of
      pups from treated dams was significantly lowered. Thus, most of the known
      toxicological properties of CP regarding systemic toxicity and
      reproductive/developmental toxicity were clearly demonstrated in this study.
      Therefore ReproTox can be considered a useful screening test for assessing repeat
      dose and reproductive/developmental toxicity of existing chemicals of high
      production volume, although teratogenic potential and adverse effects on
      spermatogenesis and fertility were not detected under the present experimental
      conditions.

PMID- 1364379
TI  - [Cholecalciferol Reference Standard (Control 901) of the National Institute of
      Hygienic Sciences].
AB  - Cholecalciferol Reference Standard for the Japanese Pharmacopoeia (JP RS) was
      prepared. The following analytical data were obtained: melting point 85.8 degrees
      C; UV and IR spectra were in agreement with both of the previous JP RS and USP RS
      of Cholecalciferol; absorptivity at 265 nm E1%lcm = 476; optical rotation
      [alpha]20D = + 110.1 degrees; no impurities were detected by TLC and HPLC
      analyses; assay 100.1% by HPLC against the USP RS. Based on the above results,
      the raw material was authorized as the Reference Standard of the National
      Institute of Hygienic Sciences.

PMID- 1364380
TI  - [Ergocalciferol Reference Standard (Control 901) of the National Institute of
      Hygienic Sciences].
AB  - Ergocalciferol Reference Standard for the Japanese Pharmacopoeia (JP RS) was
      prepared. The following analytical data were obtained: melting point 118.4
      degrees C; UV and IR spectra were in agreement with both of the previous JP RS
      and USP RS of ergocalciferol; absorptivity at 265nm E1%lcm = 467; optical
      rotation [alpha]20D = 103 degrees; no impurities were detected by TLC and HPLC
      analyses; assay 100.1% by HPLC against the USP RS. Based on the above results,
      the raw material was authorized as the Reference Standard of the National
      Institute of Hygienic Sciences.

PMID- 1364381
TI  - [Prednisolone Acetate Reference Standard (Control 901) of the National Institute
      of Hygienic Sciences].
AB  - Prednisolone Acetate Reference Standard (Control 901) for the Japanese
      Pharmacopoeia (JP RS) was prepared. The following analytical data were obtained:
      melting point 236 degrees C (decomposition); IR spectrum was same as that of JP
      RS of prednisolone acetate; absorptivity at 243 nm E1%lcm = 379; optical rotation
      [alpha]20D = +113.0 degrees; no impurity was detected by TLC, but a small amount
      of two impurities was found by HPLC analysis; assay by HPLC against the JP RS
      100.2%. Based on the above results, this raw material was authorized as the
      Reference Standard of the National Institute of Hygienic Sciences.

PMID- 1364382
TI  - [Fluocinolone Acetonide Reference Standard (Control 901) of the National
      Institute of Hygienic Sciences)].
AB  - Fluocinolone Acetonide Reference Standard (Control 901) for the Japanese
      Pharmacopoeia (JP RS) was prepared. The following analytical data were obtained:
      melting point 268 degrees C (decomposition); IR spectrum was same as the previous
      JP RS of Fluocinolone Acetonide; absorptivity at 237nm E1%1lcm = 363; optical
      rotation [alpha]20D = 105.7 degrees; no impurity was detected by TLC, but two
      impurities were detected by HPLC analysis; assay by HPLC against the previous JP
      RS 100.2%. Based on the above results, this raw material was authorized as the
      Reference Standard of the National Institute of Hygienic Sciences.

PMID- 1364383
TI  - [Diclofenamide Reference Standard (Control 891) of National Institute of Hygienic
      Sciences].
AB  - Quality of the raw material of diclofenamide was evaluated for preparation of
      "Diclofenamide Reference Standard". Analytical results for the sample were as
      follows: melting point 240 degrees C (decomposition); UV spectrum indicates
      absorption maxima at 286 and 295 nm and the absorption ratio A286/A295 1.04; IR
      spectrum is same as that of the USP Reference Standard; no impurity was found by
      TLC, but a trace of one was found by HPLC analysis; the purity is assumed to be
      99.95% by HPLC analysis; loss on drying 0.1%; assay by HPLC against USP Reference
      Standard 100.2%. Based on the results, the present raw material was authorized to
      be the Reference Standard of the National Institute of Hygienic Sciences.

PMID- 1364384
TI  - [Epitiostanol Reference Standard (Control 891) of National Institute of Hygienic
      Sciences].
AB  - The raw material of epitiostanol was examined for preparation of "Epitiostanol
      Reference Standard". Analytical results for the sample were as follows: melting
      point 130.7 degrees C (decomposition); UV spectrum indicates absorption maximum
      at 263 nm in ethanol; IR spectrum indicates specific absorption at 2920, 1383,
      1056 and 590 cm-1; optical rotation [alpha]20D+ 24.4 degrees; no impurity was
      found by TLC, but a small amount of one was found by HPLC analysis and the purity
      is assumed to be 99.5%; water content 1.52%. Based on the results, the present
      raw material was authorized to be the Reference Standard of the National
      Institute of Hygienic Sciences.

PMID- 1364385
TI  - [Methoxalene Reference Standard (Control 901) of National Institute of Hygienic
      Sciences].
AB  - The raw material of methoxalene was examined for the preparation of the
      "Methoxalene Reference Standard". Analytical data obtained were as follows:
      ultraviolet spectrum, lambda max = 300, 249 and 218 nm; absorbance, E1cm(1%) (300
      nm) = 559; infrared spectrum, same as that of USP Reference Standard of
      Methoxalene; melting point, 148 degrees C; thin-layer chromatography, no
      impurities were detected until 50 micrograms; high-performance liquid
      chromatography (HPLC), no impurities were detected, water, 0.04%; assay, 99.9% by
      absorbance method and 100.4% by the HPLC method in terms of the USP Reference
      Standard. Based on the above results, this raw material was authorized to be the
      Reference Standard of the National Institute of Hygienic Sciences.

PMID- 1364386
TI  - [Indocyanine Green Reference Standard (Control 901) of National Institute of
      Hygienic Sciences].
AB  - The raw material of indocyanine green was examined for the preparation of the
      "Indocyanine green Reference Standard (Control 901)". Analytical data obtained
      were as follows: ultraviolet and visible spectrum, lambda max = 785, 394, 216 nm;
      absorbance, E1cm(1%) (785 nm) = 3239; infrared spectrum, same as Indocyanine
      Green USP Reference Standard; sodium iodide, 4.1%; thin-layer chromatography, no
      impurities were detected until 100 micrograms; high-performance liquid
      chromatography, 4 impurities were detected; loss on drying, 1.8%; assay, 103.4%
      against USP Reference Standard. Based on the above results, this raw material was
      authorized to be the Reference Standard of the National Institute of Hygienic
      Sciences.

PMID- 1364387
TI  - [Tolnaftate Reference Standard (Control 901) of National Institute of Hygienic
      Sciences].
AB  - The raw material of tolnaftate was examined for the preparation of the
      "Tolnaftate Reference Standard". Analytical data obtained were as follows:
      ultraviolet spectrum, lambda max = 257 nm; absorbance, E1cm1% (257 nm) = 723;
      infrared spectrum, same as that of USP Reference Standard of Tolnaftate; melting
      point, 112.1 degrees C; thin-layer chromatography, no impurities were detected
      until 500 micrograms; high-performance liquid chromatography, no impurities were
      detected; loss on drying, 0%; water, 0.01%; assay, 100.4% by absorbance method
      and 100.1% by the HPLC method in terms of the USP Reference Standard. Based on
      the above results, this raw material was authorized to be the Reference Standard
      of the National Institute of Hygienic Sciences.

PMID- 1364388
TI  - [Retinol Acetate Reference Standard for Thin-layer Chromatography (Control 901)
      and Retinol Palmitate Reference Standard for Thin-layer Chromatography (Control
      901) of National Institute of Hygienic Sciences].
AB  - The raw materials of retinol acetate and retinol palmitate were examined for the
      preparation of the "Retinol Acetate Reference Standard for Thin-layer
      Chromatography" and "Retinol Palmitate Reference Standard for Thin-layer
      Chromatography", respectively. Analytical data obtained were as follows: thin
      layer chromatography, no impurities were detected in retinol acetate and one
      impurities was detected in retinol palmitate; The Rf values of retinol acetate
      and retinol palmitate were consistent with those of Reference Standards (Control
      713), respectively; ultraviolet spectrum, lambda max = 326 approximately 327 nm;
      relative extinction, within the range reported in JPXI; weight variation of
      capsules, retinol acetate 224.0 +/- 15.5 mg (RSD 6.9%), retinol palmitate 222.0
      +/- 13.8 mg (RSD 6.2%); assay, retinol acetate 57000 I.U./g, retinol palmitate
      57000 I.U./g. Based on the above results, these raw materials were authorized to
      be the Reference Standards of the National Institute of Hygienic Sciences.

PMID- 1364389
TI  - [Methylergometrine Maleate Reference Standard (Control 891) of National Institute
      of Hygienic Sciences].
AB  - The raw material of methylergometrine maleate was examined for the preparation of
      the "Methylergometrine Maleate Reference Standard". Analytical data obtained were
      as follows: melting point, 181.7 degrees C; ultraviolet spectrum, lambda max =
      313 nm; absorbance, E1%1cm (313 nm) = 181.3; infrared spectrum, 3406, 2962, 2928,
      1645, 1574 cm-1; thin-layer chromatography, 6 impurities were detected; high
      performance liquid chromatography, no impurities were detected; loss on drying,
      0.02%; optical rotation, [alpha]20D = + 44.04 degrees; assay, 99.5% against
      Ergometrine Maleate Reference Standard (Control 755). Based on the above results,
      this raw material was authorized to be the Reference Standard of the National
      Institute of Hygienic Sciences.

PMID- 1364390
TI  - [Cyclandelate Reference Standard (Control 901) of National Institute of Hygienic
      Sciences].
AB  - The raw material of cyclandelate was examined for preparation of the
      "Cyclandelate Reference Standard". Analytical data obtained were as follows:
      melting point, 60 degrees C; ultraviolet spectrum, lambda max = 252, 258 and 264
      nm E1%1cm = 6.1 (252 nm), 7.5 (258 nm), 5.9 (264 nm); infrared spectrum, 3454,
      2948, 1730, 1453, 1202, 737, 695 cm-1; thin-layer chromatography, no impurities
      were detected until 1000 micrograms; high-performance liquid chromatography
      (HPLC), one impurity was detected, loss on drying, 0.00%. Based on the above
      results, this raw material was authorized to be the Reference Standard of the
      National Institute of Hygienic Sciences.

PMID- 1364391
TI  - [Potassium Sucrose Octa Sulfate Reference Standard (Control 901) of National
      Institute of Hygienic Sciences].
AB  - The raw material of potassium sucrose octa sulfate was examined for the
      preparation of the "Potassium sucrose octa sulfate Reference Standard (Control
      901)". Analytical data obtained were as follows: infrared spectrum, 3494, 1642,
      1247, 1002, 795, 584 cm-1; high-performance liquid chromatography, 3 impurities
      were detected; water, 6.2%; assay of sucrose octa sulfate, 99.1%. Based on the
      above results, this raw material was authorized to be the Reference Standard of
      the National Institute of Hygienic Sciences.

PMID- 1364392
TI  - [Riboflavin Reference Standard (Control 891) of National Institute of Hygienic
      Sciences].
AB  - The raw material of riboflavin was examined for the preparation of the
      "Riboflavin Reference Standard (Control 891)". Analytical data obtained were as
      follows: melting point, 238.2 degrees C (decomposition); absorbance, E1%1cm = 859
      (267 nm), 277 (372 nm), 327 (445 nm); infrared spectrum, same as Riboflavin
      Reference Standard (Control 872); thin-layer chromatography, 5 impurities were
      detected; high-performance liquid chromatography, 11 impurities were detected;
      loss on drying, 0.25%; optical rotation, [alpha]20D = -133.6 degrees; solubility,
      less than 16 min; assay, 100.1% against Riboflavin Reference Standard (Control
      872). Based on the above results, this raw material was authorized to be the
      Reference Standard of the National Institute of Hygienic Sciences.

PMID- 1364393
TI  - [d-Camphor Reference Standard (Control 901) and dl-Camphor Reference Standard
      (Control 901) of National Institute of Hygienic Sciences].
AB  - The raw materials of d-camphor and dl-camphor were examined for the preparation
      of the "d-Camphor Reference Standard" and "dl-Camphor Reference Standard".
      Analytical data obtained were as follows: ultraviolet spectrum, lambda max = 257
      nm; absorbance, E1%1cm(257 nm) = 723; infrared spectrum, 2956, 1742, 1045 cm-1;
      optical rotation, [alpha]20D = +42.9 degrees (d-camphor), [alpha]20D = -0.00
      degrees (dl-camphor); melting point, 180 degrees C (d-camphor), 179 degrees C (dl
      camphor); gas-chromatography, one impurity was detected in d-camphor and four
      impurities were detected in dl-camphor. Based on the above results, these raw
      materials were authorized to be the Reference Standards of the National Institute
      of Hygienic Sciences.

PMID- 1364394
TI  - [Estimated production by the official inspection of coal-tar dyes (including dye
      aluminum lakes) in 1990 based on official inspection figures].
AB  - The number of official inspections of coal-tar dyes and their lakes from april in
      1990 till march in 1991 was 836 in total. The quantity passed amounted to 238 ton
      in Japan. The production of color for each month was summarised in Table 1, and
      by each producing company in Table 2. The food coal-tar dye produced in the
      largest quantity was Food Yellow No. 4, occupying 46.2% in this period.

PMID- 1364395
TI  - [Combined chronic toxicity/carcinogenicity test of tris(2-chloroethyl)phosphate
      (TCEP) applied to female mouse skin].
AB  - Tris(2-chloroethyl)phosphate (TCEP), a widely used flame retardant, was tested
      for its skin chronic toxicity/carcinogenicity using female Slc: ddY mice. TCEP (5
      and 50%) dissolved in ethanol was applied to the shaved skin twice a week for 79
      weeks. The control group received ethanol under similar condition. In addition, 5
      animals in each group were killed at 6 and 12 months and used for the chronic
      toxicity study. In body weight, food consumption and survival rate, there was no
      significant difference between the control and treated groups. Spleen weight was
      decreased in the 50% group. No significant difference in the incidence of tumors
      and other non-neoplastic lesions of the skin and other organs was found between
      the control and treated groups. The results indicate that under the conditions of
      the present study, TCEP has no carcinogenicity and toxicity for the skin.

PMID- 1364396
TI  - [Studies on "Erythrosine Standard", Dye Standards of National Institute of
      Hygienic Sciences].
AB  - "Erythrosine Standard (C.I. 45430)", Dye Standards of National Institute of
      Hygienic Sciences, was prepared. The content of this Dye Standard was determined
      by the gravimetric method. This content averaged 99.1%. Ultra violet-visible
      absorption and infrared spectra of the Dye Standard were also determined.

PMID- 1364397
TI  - [Studies on "brilliant blue FCF standard", dye standards of National Institute of
      Hygienic Sciences].
AB  - "Brilliant Blue FCF Standard (C.I. 42090)", Dye Standards of National Institute
      of Hygienic Sciences, was prepared. The content of this Dye Standards was
      determined by titanium trichloride method. This content averaged 96.3%. Ultra
      violet-visible absorption and infrared spectra of the Dye Standard were also
      determined.

PMID- 1364398
TI  - [Studies on "Tartrazine Standard", Dye standards of National Institute of
      Hygienic Sciences].
AB  - "Tartrazine Standard (C.I. 19140)", Dye Standards of National Institute of
      Hygienic Sciences, was prepared. The content of this Dye Standard was determined
      by the titanium trichloride method. This contents averaged 99.0%. Ultra violet
      visible absorption and infrared spectra of the Dye Standard were also determined.

PMID- 1364399
TI  - [Studies on "allura red AC standard", dye standards of National Institute of
      Hygienic Sciences].
AB  - "Allura Red AC Standard (C.I. 16035)", Dye Standards of National Institute of
      Hygienic Sciences was prepared. The content of this Dye Standards was determined
      by the titanium trichloride method. This content averaged 95.5%. Ultra violet
      visible absorption and infrared spectra of the Dye Standard were also determined.

PMID- 1364400
TI  - [Acute and subacute toxicity studies of Bis(2,3-dibromopropyl) phosphate
      magnesium in rat].
AB  - Acute and subacute oral toxicity tests of Bis(2,3-dibromopropyl) phosphate
      magnesium (Bis-BP.Mg) were carried out in Wistar rats. In the acute toxicity
      test, Bis-BP.Mg suspended in arabic gum was administered orally to a group
      consisting of 10 male and 10 female rats, and they were observed for 14 days.
      LD50 values of male and female rats were 283 (253 approximately 314) mg/kg and
      261 (219 approximately 310) mg/kg, respectively. As toxic symptoms, eyelid
      closure, crouching, shivering and staggering gait were observed in the treated
      groups of both sexes. In gross findings, hypertrophy, discoloration and necrotic
      change of the liver, and hypertrophy and discoloration of the kidney were
      observed in the treated groups. In histopathological examination, necrosis,
      desquamation, large nuclei formation of the tubular epithelium, and tubular
      dilatation of the kidney and necrosis of the liver cells were observed in the
      treated groups. In the subacute toxicity test, groups of rats consisting of 5
      males and 5 females were fed a commercial diet containing 0, 30, 100, 300 and
      1000 ppm Bis-BP.Mg for 45 days. In body weight and food consumption, there were
      no significant difference between the control and treated groups. Significant
      increases were observed in the liver and kidney weights of male rats fed 1000 ppm
      Bis-BP.Mg. Histopathologically, desquamation, swelling, and large nuclei
      formation of the tubular epithelium and tubular dilatation of the kidney were
      observed, but they were much less frequent than those in the acute toxicity test.
      It was concluded that Bis-BP.Mg has apparent renal toxicity.

PMID- 1364401
TI  - [Studies on the uptake of 8-anilino-1-naphthalene sulfonate by rat freshly
      isolated renal cells].
AB  - The addition of 8-anilino-1-naphthalene sulfonate (ANS) into rat renal cell
      suspension caused a rapid increase in fluorescence (Ex. 400 nm, Em. 470 nm). The
      increase in fluorescence seemed to be composed of two phases. When the cells were
      disrupted by ultrasonic wave, the fast phase (0-ca 20 sec) increased and the slow
      phase (after ca 40 sec) disappeared. The rate of increase in the slow phase was
      dependent on the concentration of ANS and on the ambient temperature. A double
      reciprocal plot of the rate and the concentration exhibited straight line. It was
      decreased by bromophenol blue and rose bengal but not by other organic anions
      like p-aminohippuric acid and several metabolic inhibitors. It seemed that the
      uptake of ANS into the renal cell is mediated by a carrier which is different
      from that for p-aminohippuric acid.

PMID- 1364402
TI  - [Studies on the teratogenic potential of 2,2'-isobutylidene-bis (4,6
      dimethylphenol) in rats].
AB  - 2,2'-Isobutylidene-bis(4,6-dimethylphenol), an antioxidant, was given orally to
      pregnant Wistar rats by stomach intubation at the dose levels of 5, 15 or 45
      mg/kg body weight during days 7 to 17 of gestation, and the effects of the
      compound on dams and fetal developments were examined. In the dams at the two
      higher dose levels of 15 and 45 mg/kg, toxic signs (tremor, startle reflex,
      salivation, involuntary urination, wheezing and nostril discharge) were observed.
      Moreover, at the highest dose level, additional toxic signs (lacrimation and
      vaginal bleeding), suppression in maternal body weight gain and food consumption
      were observed. However, there was no evidence of an increase in malformations
      attributable to the treatment with 2,2'-isobutylidene-bis(4,6-dimethyl-phenol) in
      any of the treated groups. It was concluded that 2,2'-isobutylidene-bis(4,6
      dimethylphenol) has no teratogenic effect in rats, though toxic signs were
      observed in treated dams of the 15 and 45 mg/kg groups.

PMID- 1364403
TI  - [Twenty-eight-day repeated dose toxicity test of p-phenetidine in F344 rats].
AB  - A twenty-eight-day repeated dose toxicity test of p-phenetidine was carried out
      in male and female F344 rats at dose levels of 160, 40, 10 or 0 mg/kg/day. Thirty
      animals of both sexes were divided into 6 groups of equal number. All groups were
      treated daily by i.g. administration for 28 days, two extra groups of animals at
      dose levels of 160 and 0 mg/kg being used for investigation of recovery over 14
      days. Hematological and urinary examinations revealed decrease in erythrocytes
      and increased serum reticulocytes and urinary urobilinogen in the 160 and 40
      mg/kg groups of both sexes, and methemoglobinemia occurred in the 160 mg/kg
      group. Increase in spleen weight was noted in the 160 and 40 mg/kg groups. On
      histopathological examination, hemosiderosis, increased extramedullary
      hemopoiesis, congestion of the spleen and myeloid hyperplasia of the bone marrow
      were observed in the 160 and 40 mg/kg groups of both sexes. Repair of these
      lesions occurred within 14 days after the cessation of administration. Based on
      these findings, a no-observed-effect level for p-phenetidine would be concluded
      10 mg/kg/day.

PMID- 1364404
TI  - [Subchronic oral toxicity study of stevioside in F344 rats].
AB  - A 13-week subchronic oral toxicity study of stevioside was carried out in F344
      rats at dose levels of 0, 0.31, 0.62, 1.25, 2.5 and 5% in diet, to determine
      appropriate dose levels for a 2-year carcinogenicity study. The rats were
      randomly allocated to 6 groups, each consisting of 10 males and 10 females. No
      animals died during the administration period. Between the control and treated
      groups, there were no differences in body weight gain during the administration
      period and in food consumption in the later period of the study. LDH on
      biochemical investigation and single cell necrosis in the liver revealed by
      histopathological examination were increased in all male treated groups. These
      were not considered specific changes, because of the lack of any clear dose
      response, the relatively low severity and the limitation to males. Other
      parameters that were found to demonstrate significant differences on
      hematological and biochemical investigations were of minor toxicological
      significance. From these results, a concentration of 5% in diet was concluded to
      be a suitable maximum tolerable dose of stevioside for a 2-year carcinogenicity
      study in rats.

PMID- 1364405
TI  - [Dose-response relationship of promotion by phenobarbital in rat two-stage
      hepatocarcinogenesis].
AB  - Investigation of the effect of various doses of phenobarbital (PB) in Experiment
      I (PB dose levels: 0, 38, 75, 150, 300 or 600 ppm) and Experiment II (PB dose
      levels: 0, 1, 4 or 16 ppm) given to male F344 rats (20 animals/group) in drinking
      water for 39 weeks after a single intraperitoneal injection of diethylnitrosamine
      (DEN) was performed using incidence of hepatic tumors and number or area of
      enzyme-altered foci as end-point lesions. There were no significant differences
      in the final body weight changes between DEN-initiated PB treatment (DEN+PB) and
      DEN-initiated (DEN) groups. Dose-dependent increases in the absolute and relative
      liver weights and in the incidence of hepatic carcinoma were found in the DEN+PB
      groups treated with 38 ppm PB or above 75 ppm PB or above, respectively. The
      numbers or areas of gamma-GTP or GST-P positive foci of the liver were increased
      in the DEN+PB groups treated with 38 ppm PB or above. Additional investigation of
      7-ethoxycoumarin o-deethylase (7-ECDE) induction in Experiment III, 7 groups
      consisting of 3 animals/group being fed water containing PB (0, 1, 4, 16, 75, 300
      or 1200 ppm) for 1 week after the initiation of DEN and a further 7 groups (5
      rats/group) receiving the same drinking water without DEN treatment, revealed
      dose-dependent increases of 7-ECDE in the DEN+PB groups and PB groups treated
      with 16 ppm PB or above. The present studies indicate that the threshold for
      promotion by PB is 38 ppm.

PMID- 1364406
TI  - [Subchronic oral toxicity study of cyanoguanidine in F344 rats].
AB  - A 13-week subchronic oral toxicity study of cyanoguanidine was performed in male
      and female F344 rats by feeding of CRF1 powder diets containing 0, 1.25, 2.5, 5
      and 10% cyanoguanidine to determine appropriate dose levels for a subsequent 2
      year carcinogenicity study. The rats were randomly allocated to 5 groups, each
      consisting of 10 males and 10 females. No animals died during the administration
      period. Inhibition of body weight gain was more marked in both sexes of the 10%
      group and in females of the 5% group as compared with the control group. Mean
      food intake in males of the groups treated with 5% or 10% and in females of the
      10% group was significantly higher than that in the control group. Serum
      biochemical investigation revealed a higher level of serum BUN in both sexes of
      the 10% group. On histopathological examination, toxic changes characterized by
      the occurrence of intranuclear eosinophilic inclusion bodies in the proximal
      tubular epithelium of the kidney were observed in both sexes of the 10% group.
      Similar inclusion bodies were also seen in 2 out of 10 males of the 5% group.
      From these results, it was concluded that a level of 10% of cyanoguanidine in the
      diet is unequivocally toxic. A dose level, 5% cyanoguanidine, in the diet might
      be appropriate as a high dose for a carcinogenicity study.

PMID- 1364407
TI  - [Ultrastructural study of the blood-testis barrier in rat by the lanthanum
      method].
AB  - Ultrastructural changes of the testes in 35-week-old WBN/Kob rats were
      investigated using the lanthanum-tracer method. Tissues were cut and fixed with a
      solution containing 1% lanthanum and 2% glutaraldehyde in a 0.1 M sodium
      cacodylate buffer at pH 7.8 and with a solution of 2% osmium and 1% lanthanum in
      a 0.1 M sodium cacodylate buffer. Ultrathin sections of epoxy resin-embedded
      specimens were stained with uranyl acetate and lead citrate and observed into a
      JEM-100CXS JEOL transmission electron microscope. The remnants of each testis
      were fixed in Bouin's fixative, and observed light-microscopically, where almost
      all seminiferous tubules in all of the six testes were found to be severely
      atrophied. Electron microscopically, lanthanum pigments were limited in the
      Sertoli cell tight junctions of the seminiferous tubules even in the severely
      atrophied tubules. In conclusion, it is unlikely that the testicular atrophy in
      WBN/Kob rats is attributable to dysfunction of the blood-testis barrier.

PMID- 1364408
TI  - [Twenty-eight day repeated dose toxicity test of m-nitroaniline in F344 rats].
AB  - A twenty-eight day repeated oral dose toxicity test of m-nitroaniline (m-NA) was
      carried out in male and female F344 rats at dose levels of 0, 15, 50 or 170
      mg/kg/day. Animals of both sexes were divided into 6 groups, each consisting of
      30 animals, 4 groups being used for the 28 days dosing study and the remainder
      for investigation of subsequent recovery. Inhibition of body weight gain, and
      induction of cyanosis and methemoglobinemia were observed in the highest dose
      groups of both sexes, but there were no animal mortalities. Testicular atrophy
      was evident but there was no effect on the ovaries in the same group. In addition
      to these findings, hemolytic anemia and increases of liver, spleen and kidney
      weights were also observed in both sexes in a dose-related fashion.
      Histologically, the highest dose group showed reduction of spermatogenesis with
      multinucleated giant cell formation, lipofuscin deposition mainly in the proximal
      renal tubules, and increases in hemosiderin deposition and extramedullary
      hematopoiesis in the liver. Dose-related increases in the incidence of
      hemosiderin deposition in the spleen, erythroid hyperplasia in the bone marrow
      and swelling of hepatocytes were observed in treated groups. After a 14 day
      recovery period, these findings were attenuated or had disappeared. Based on
      these results obtained under the present experimental conditions, it was
      concluded that m-NA induces hemolytic anemia and exerts testicular toxicity in
      rats and that the non-observed-effect level of m-NA is less than 15 mg/kg/day.

PMID- 1364409
TI  - Stability of vitamin B1 in a commercial multivitamin syrup preparation.
AB  - Accelerated stability studies of a commercial vitamin B1 syrup preparation were
      carried out at 50, 60, 70 and 80 degrees C. The decomposition of vitamin B1 in
      the preparation followed pseudo-first order reaction kinetics. Apparent
      decomposition rate constants conformed to the Arrhenius equation. Apparent
      activation energy and shelf-life at 25 degrees C were estimated to be 24.2
      kcal/mol and 3.3 years, respectively.

PMID- 1364410
TI  - [Up-dating the references for environmental health criteria for anionic
      surfactants and preparation of its first draft].
AB  - The preparation of a EHC monograph for anionic surfactants was started in 1980.
      The chemicals consist of linear alkylbenzene sulfonate (LAS), alkyl sulfate (AS)
      and alkyl alpha-olefin sulfonate (AOS). Although a preliminary draft appeared in
      1985, further works were stopped for 5 years. For the development of the
      preliminary draft, up-dating the references was performed by using on-line JICST
      data base from 1981 to 1990. The number of literature on LAS was 486. On the
      other hand the number on AS was about 1/5 that of LAS. In the case of AOS, only
      20 literatures were retrieved. The literatures on LAS were many in the research
      field of environmental science and very few in the toxicology field.

PMID- 1364411
TI  - [Improvements of commentary work on the first drafts of the EHC monographs].
AB  - The EHC is historically most important among the activities of IPCS which was
      inaugurated in 1980, and its first draft is being circulated to IPCS contact
      points throughout the world. Comments and suggestions in improvements to the
      first draft of the EHC monograph is essential to the sound development of this
      document. Our suggestions on such improvements are the basis of this report.

PMID- 1364412
TI  - [Comparative studies on acute toxicity of glutaraldehyde using young and old
      rats].
AB  - Acute oral toxicity test of glutaraldehyde (GA) was carried out in young (5-6W)
      and old (57-60W) Wistar/ST rats. Experiment 1: Various doses of GA were
      administered by gavage. After 30 minutes, the rats showed abnormal gait, then
      took an abdominal or lateral position after 4 hours. Gross erosion, discoloration
      and thickening of the glandular stomach mucosa and hyperemia of the liver,
      intestine and lung were observed in the dead rats. The LD50 values were 283 mg/kg
      for young rats and 141 mg/kg for old rats. Experiment 2: One half of the LD50
      doses (140 mg/kg and 70 mg/kg of GA) were administered to young and old rats by
      gavage, respectively. Both groups showed a similar toxicity. Organ weights were
      not changed. In gross findings, erosion, discoloration and thickening of the
      glandular stomach mucosa were observed on day 1-7, but these damages were
      recovered by day 14. Histopathologically, atrophy, degeneration, necrosis,
      hemorrhage, edema and cell infiltration of the glandular stomach mucosa were
      found on day 1. Recovery from these changes was observed from day 3. Changes in
      several serum enzyme activities were observed on day 1-3. Therefore,
      susceptibility to the acute toxic effect of GA was higher in old rats than in
      young rats. However, no apparent differences were observed in the toxic profiles
      by GA between young and old rats.

PMID- 1364413
TI  - [Survey of radiocesium in domestic mushrooms on the market].
AB  - Domestic mushrooms on the market were tested for concentration of radiocesium;
      cesium-134 and 137 by gamma-ray spectrometer. Cesium-137 was detected in most
      samples of dried and raw shiitake (Lentinus edodes (Berk.) Sing.). The
      concentrations were from 6.7 to 73.9 Bq/kg in dried ones and from 1.3 to 6.4
      Bq/kg in raw ones. It was not detected in enokitake (Flammulina veltipes (Fr.)
      Sing.) and shimeji (Lyophyllum aggregatum (Secr.) Kuhner and Pleurotus ostreatus
      (Fr.) Quel.). Cesium-134 was not found in all samples.

PMID- 1364414
TI  - [Studies on origin of illicit methamphetamine. I. The relationship of
      enantiomeric compositions between methamphetamine and its raw material
      (ephedrine)].
AB  - In order to elucidate the relationship of enantiomeric compositions between
      methamphetamine (MA) and its raw materials, ephedrine (EP) enantiomers,
      commercial EP samples and MA samples prepared from them were analyzed by HPLC
      using GITC-prelabeling. The GITC derivatives were separated on ODS column using
      methanol-water-acetic acid (45:54:1) at a flow rate of 1.2 ml/min for EP and
      tetrahydrofuran-water-acetic acid (29:70:1) at a flow rate of 1 ml/min for MA.
      The chromatographic conditions resulted in such a good separation of four EP and
      two MA enantiomers that 1/1000 enantiomeric impurities could be detected and
      discriminated from the major enantiomer with good reproducibility. Moreover, it
      was demonstrated that the asymmetric center at alpha-position of amino group was
      entirely retained throughout the reductive reaction of the EP samples, and that
      the MA samples inherited the enantiomeric character from the EP samples used.
      This method was applied to discriminative analysis of MA samples seized in Japan.

PMID- 1364415
TI  - [Development of a database for registration of journals in the library of NIHS].
AB  - A database for registration and management of journals in the library of NIHS was
      developed using dBASE III PLUS software. The database was shown to be useful in
      searching for journals subscribed in the various divisions of NIHS and for those
      already expired. Additional data related to accounting on and arrangement of
      journals will help management of the library.

PMID- 1364416
TI  - [Lysozyme reference standard (control 911) of National Institute of hygienic
      Sciences].

PMID- 1364417
TI  - [Pyridoxine hydrochloride reference standard (Control 911) of the National
      Institute of Hygienic Sciences].
AB  - The raw material of pyridoxine hydrochloride was examined for preparation of the
      "Pyridoxine Hydrochloride Reference Standard". Analytical data obtained were as
      follows: loss on drying, 0.00%; pH, 2.87; melting point, 204.6 degrees C
      (decomposition); infrared spectrum, same as Pyridoxine Hydrochloride Reference
      Standard (Control 879); thin-layer chromatography, nonimpurities were detected;
      assay, 100.0% by non-aqueous titration and 100.0% by UV spectrophotometry. Based
      on the above results, the raw material was authorized as the Japanese
      Pharmacopoeia Standard (Control 911).

PMID- 1364418
TI  - [Tocopherol reference standard (Control 911) of the National Institute of
      Hygienic Sciences].
AB  - The raw material for tocopherol was tested for preparation of the "Tocopherol
      Reference Standard (Control 911)". Analytical data obtained were as follows:
      infrared spectrum, same as Tocopherol Reference Standard (Control 881);
      absorptivity, E1%1cm (292nm) = 75.5; thin-layer chromatography, no impurities
      were detected up to 50.0 micrograms; high performance liquid chromatography
      (HPLC), four impurities were detected; assay, 100.7% by HPLC. Based on the above
      results, the raw material was authorized as the Japanese Pharmacopoeia Standard
      (Control 911).

PMID- 1364419
TI  - [Prednisolone reference standard (Control 911) of the National Institute of
      Hygienic Sciences].
AB  - Prednisolone was tested for preparation of the "Prednisolone Reference Standard
      (Control 911)". The quality of raw material was examined and compared with the
      previous Reference Standard (Control 872). Analytical data obtained were as
      follows: loss on drying, 0.10%; melting point, 233.2 degrees C (decomposition);
      optical rotation, [alpha]20D+98.77 degrees; UV spectrum, lambda max = 243nm;
      absorptivity, E1%1cm (243nm) = 413.5; IR spectrum, 1711, 1612, 1110, 888cm-1; one
      impurity was detected by thin-layer chromatography and high-performance liquid
      chromatography (HPLC), respectively; assay, 100.1% by HPLC. Based on the above
      results, the raw material was authorized as the Japanese Pharmacopoeia Standard
      (Control 911).

PMID- 1364420
TI  - [d-Camphor reference standard (Control 911) and dl-Camphor Reference Standard
      (Control 911) of the National Institute of Hygienic Sciences].
AB  - The raw materials of d-camphor and dl-camphor were examined for preparation of
      the "d-Camphor Reference Standard" and "dl-Camphor Reference Standard".
      Analytical data obtained were as follows: ultraviolet spectrum, lambda max =
      290nm; infrared spectrum, 2958, 1742, 1045cm-1; optical rotation, [alpha]D20 =
      +42.7 degrees (d-camphor), [alpha]D20 = -0.3 degrees (dl-camphor); melting point,
      180 degrees C (d-camphor), 179 degrees C (dl-camphor); gas-chromatography (GC),
      one impurity was detected in d-camphor and three impurities in dl-camphor; assay,
      99.5% (d-camphor), 99.5% (dl-camphor) by GC. Based on the above results, these
      raw materials were authorized as the Japanese Pharmacopoeia Standard (Control
      911).

PMID- 1364421
TI  - [Tocopherol acetate reference standard (Control 911) of the National Institute of
      Hygienic Sciences].
AB  - The raw material for tocopherol acetate was tested for preparation of the
      "Tocopherol Acetate Reference Standard (Control 911)". Analytical data obtained
      were as follows: infrared spectrum, same as Tocopherol Acetate Reference Standard
      (Control 881); absorptivity, E1cm1% (284nm) = 43.5; thin-layer chromatography, no
      impurities were detected up to 50.0 micrograms; high performance liquid
      chromatography (HPLC), two impurities were detected; assay, 100.3% by HPLC. Based
      on the above results, the raw material was authorized as the Japanese
      Pharmacopoeia Standard (Control 911).

PMID- 1364422
TI  - [Quality tests for ibuprofen preparations].
AB  - Ibuprofen preparations were tested with a view to checking their quality by
      physical methods such as determination, disintegration and dissolution tests.
      These studies were carried out on 48 kinds of commercial ibuprofen preparations.
      The drug content of each preparation was measured by spectrophotometry (264nm),
      and the values were in the range of 90-110%. In the disintegration tests of 36
      tablets, a few tablets of two preparations failed to disintegrate completely
      after 60 minutes. However the number of such tablets was within the limit
      specified in JP. The dissolution test described in the USP monograph was also
      applied to the 36 tablets, and it was found that 9 tablets failed the test
      provision that over 70% of the tablets must be dissolved within 30 minutes.

PMID- 1364423
TI  - [Studies on the analysis of copper chlorophyll and sodium copper chlorophyllin in
      imported foods].
AB  - The analysis of copper chlorophyll (CuCh) and sodium copper chlorophyllin (CuCh
      Na) in imported foods was carried out. Standards of CuCh and CuCh-Na were
      examined by ultraviolet and visible spectrophotometer. CuCh gave absorption
      maximum around 650 nm, while CuCh-Na gave around 630 nm. Imported sweets and
      liqueurs were homogenized and extracted with ethyl acetate. These extracts also
      gave absorption maxima absorbance around 650 nm or 630 nm. The results suggested
      that a distinction between CuCh and CuCh-Na in foods was possible by
      spectrophotometry. Visible spectrophotometric quantitation was also tried.
      However the estimated levels of CuCh or CuCh-Na in the samples by this method did
      not meet with those by atomic absorption spectrometry.

PMID- 1364424
TI  - [Estimated production of coal-tar dyes (including dye aluminum lakes) based on
      official inspections in 1991].
AB  - The total number of official inspection of coal-tar dyes and their lakes from
      April in 1991 to March 1992 was 835. The quantity which passed inspection
      amounted to 240 tons in Japan. The official production of color dyes each month
      in summarised in Table 1 and that by various manufacturers in Table 2. The food
      coal-tar dye produced in the largest quantity was Food Yellow No. 4, occupying
      44.6% of the total during this period.

PMID- 1364425
TI  - [Studies on "new coccine standard" for the dye standard of the National Institute
      of Hygienic Sciences].
AB  - The "New Coccine Standard (C.I. 16255)" for the Dye Standard of the National
      Institute of Hygienic Sciences was prepared. The content of this Dye Standard
      determined by the titanium trichloride method was 97.5% on the average. The
      ultraviolet-visible absorption and infrared spectra of the Dye Standard were also
      measured.

PMID- 1364426
TI  - [Studies on "acid red standard" for the dye standard of the National Institute of
      Hygienic Sciences].
AB  - The "Acid Red Standard (C.I. 45100)" for the Dye Standard of the National
      Institute of Hygienic Sciences was prepared. The content of this Dye Standard
      determined by the titanium trichloride method was 96.4% on the average. The
      ultraviolet-visible absorption and infrared spectra of the Dye Standard were also
      measured.

PMID- 1364427
TI  - [Studies on "indigo carmine standard" for the dye standard of the National
      Institute of Hygienic Sciences].
AB  - The "Indigo Carmine Standard (C.I. 73015)" for the Dye Standard of the National
      Institute of Hygienic Sciences was prepared. The content of this Dye Standard
      determined by the titanium trichloride method was 97.0% on the average. The
      ultraviolet-visible absorption and infrared spectra of the Dye Standard were also
      measured.

PMID- 1364428
TI  - [Analytical results of post-harvest pesticides in citrus fruits and fruits juices
      by GC-MS (SIM) and HPLC with fluorescent detector].
AB  - Determination of 6 kinds of post-harvest pesticides (DP, OPP, TBZ, 2,4-D,
      Imazalil and Benomyl) in citrus fruits and fruits juices was carried out by GC-MS
      (SIM) and HPLC with fluorescent detector. DP for 16 samples, OPP for 27 samples,
      TBZ for 12 samples, 2,4-D for 10 samples, imazalil for 20 samples and Benomyl for
      4 samples were detected in total 32 samples.

PMID- 1364429
TI  - Determination of organophosphorus pesticides in imported foods by FPD-GC and GC
      MS.
AB  - Organophosphorus pesticides in 47 agricultural products imported at the Yokohama
      and Kobe Quarantine Station in 1990 were determined by FPD-GC and identified by
      GC-MS. Chlorpyrifosmethyl, malathion and fenitrothion were found in wheat (0.03
      0.69 ppm), chlorpyrifosmethyl and fenitrothion in soy bean (0.02-1.03 ppm),
      chlorpyrifosmethyl in cherry (0.12-0.17 ppm), chlorpyrifosmethyl in pumpkin (0.07
      0.15 ppm), chlorpyrifosmethyl and malathion in corn (0.15-1.38 ppm).

PMID- 1364430
TI  - [Studies on reinforcing effects of methylephedrine, caffeine and their mixture
      with intravenous-self administration in rhesus monkeys].
AB  - The reinforcing effects of methylephedrine hydrochloride (ME), anhydrous caffeine
      (CA) and their mixture (ME+CA) were studied by the intravenous cross self
      administration experiment and by the progressive ratio experiment in four male
      rhesus monkeys each. In the intravenous cross self-administration experiment, ME,
      CA and ME+CA were found to have reinforcing effects. Self-administration rates
      above the level of cocaine, a typical reinforcing drug, were not observed in ME
      or CA alone, but observed in their mixture (120 + 126 micrograms/kg/inj.: M dose
      or 480 + 504 micrograms/kg/inj.: H dose). The minimum reinforcing doses were 120
      micrograms/kg/inj. (M dose) for ME, 126 micrograms/kg/inj.: (M dose) for CA, and
      ME 30 micrograms+CA 32 micrograms/kg/inj. (L dose) for the mixture. Vomiting was
      observed during the session in monkeys which showed higher self-administration
      rates of ME and the mixture, and decreases in the rates were observed in these
      animals on the next day. One animal at H dose of the mixture, which showed a high
      self-administration rate on both the 1st and 2nd days, died after the end of the
      session on the 2nd day. In the progressive ratio experiment, the final ratios at
      120 micrograms/kg/inj. of ME, 126 micrograms/kg/inj. of CA and the mixture of ME
      120 micrograms/CA 126 micrograms/kg/inj. were almost equal to or less than that
      of saline (negative control). Thus, these drugs didn't show reinforcing effects
      at the above levels. However, a reinforcing effect was observed in three out of
      four monkeys administered 1920 micrograms/kg/inj. of ME, 2016 micrograms/kg/inj.
      of CA, and the mixture of ME 1920 and CA 2016 micrograms/kg/inj.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1364431
TI  - [Studies on the teratogenic potential of p-tert-butylphenolformaldehyde resin in
      rats].
AB  - p-tert-Butylphenolformaldehyde resin, an adhesive, was given orally to pregnant
      Wistar rats by stomach intubation at the dose levels of 250, 500 and 1000 mg/kg
      body weight during days 7 to 17 of gestation, and the effects of the compound on
      dams and fetal developments were examined. No changes in general conditions,
      maternal body weight, food consumption, numbers of corpora lutea and implantation
      ratio were observed. There was no evidence of an increase in fetal death or of
      malformation attributable to the treatment with p-tert-butylphenolformaldehyde
      resin in any of dose levels examined. It was concluded that p-tert
      butylphenolformaldehyde resin has no teratogenic effect in rats.

PMID- 1364432
TI  - [Twenty-eight day repeated dose toxicity test of dihepthyl phthalate in F344
      rats].
AB  - A twenty-eight day repeated oral dose toxicity test of dihepthyl phthalate (DHP)
      was carried out in male and female F344 rats at the dose levels of 0, 0.2, 1 and
      5 g/kg/day. All rats in each group, consisting of 5 males and 5 females, received
      a daily intragastric administration of DHP for 28 days. Additional two groups of
      animals exposed to dose levels of 0 and 5 g/kg were used for investigation of
      subsequent recovery for 2 weeks. No animals died during the administration
      period. Inhibition of body weight gain was observed in both sexes of the 5 g/kg
      group. Blood biochemistry revealed significant increases in albumin and A/G ratio
      in males of the groups treated with 0.2 g/kg or more, and in albumin and total
      protein in females treated with 1 g/kg or more. In the 5 g/kg group, BUN, GOT,
      GPT, ALP and Zn was increased in males, and GOT in females. The increases in GOT,
      GPT and ALP were also observed in males of the 1 g/kg group. Increases in liver
      and kidney weights were noted in both sexes treated with 1 g/kg or more and in
      males of the 5 g/kg group, respectively. Testicular weight was decreased in the 5
      g/kg group. On histopathological examination, swelling and necrosis of
      hepatocytes were found in males of the 1 and 5 g/kg groups. Males of the 5 g/kg
      group showed atrophy of the seminiferous tubules accompanied with loss of
      spermatogenesis. In the recovery group, similar changes were detected in the
      testis, but some of the seminiferous tubules showed slight regenerative
      changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364433
TI  - [Twenty-eight-day repeated dose toxicity test of pentaerythritol in F344 rats].
AB  - A twenty-eight-day repeated dose toxicity test of pentaerythritol at dose levels
      of 1000 or 0 mg/kg/day was carried out in male and female F344 rats. Thirteen
      animals of each sex were divided into 2 groups with 7 rats receiving
      pentaerythritol treatment and 6 rats served saline as control. All groups
      received an i.g. administration daily for 28 days. As to serum biochemical and
      hematological examinations, there were no serious differences between the
      pentaerythritol-treated rats and the control rats. On histopathological
      examination, no specific changes were observed in the pentaerythritol-treated
      rats. Based on these results, the no-observed-effect level of pentaerythritol can
      be concluded to be more than 1000 mg/kg/day.

PMID- 1364434
TI  - [Studies on cell proliferation activities in acute toxic lesions in the liver and
      pancreas of hamsters treated with N-nitrosobis(2-oxopropyl)amine].
AB  - Histopathology and cell proliferation activities in acute toxic lesions in the
      liver and pancreas of female Syrian hamsters given a S.C. injection of N
      nitrosobis(2-oxopropyl)amine (BOP) at a dose of 100 mg/kg, were investigated.
      Histologically, at one day after administration, hypertrophy and focal necrosis
      of the hepatocytes were observed, whereas no remarkable changes were seen in the
      pancreas. At 7 days after administration, when diffuse hypertrophy, vacuolation
      and necrosis of the hepatocytes, and atypical hyperplasia of the bile duct were
      seen in the liver, hyperplasia of the pancreatic duct and focal necrosis and
      vacuolation of the acinar cells were noticed in the pancreas.
      Immunohistochemistry for both 5-bromodeoxyuridine (BrdU) and proliferating cell
      nuclear antigen (PCNA) revealed remarkable increases of cell proliferation
      activities in the target cells for BOP toxicity, especially at 7 days after BOP
      treatment. Meanwhile, the number per nucleus of silver-stained proteins related
      to nucleolar organizer regions (AgNOR) was significantly increased in the target
      cells at both 1 and 7 days after BOP treatment. Thus, in the present study, it
      was suggested that acute toxic changes in the liver of hamsters treated with BOP
      precedes those in the pancreas. The speculation that AgNOR may be an indicator
      recognizing earlier alterations on acute BOP toxicity remains to be examined.

PMID- 1364435
TI  - [13-week subchronic toxicity study of 1,1-bis(t-butylperoxy) 3,3,5-trimethyl
      cyclohexane in mice].
AB  - A 13-week subchronic toxicity study of 1,1-bis(t-butylperoxy)3,3,5-trimethyl
      cyclohexane (TMCH) was performed in male and female B6C3F1 mice by feeding a CRF
      1 powder diet containing 0, 0.5, 1.0, 2.0 and 4.0% TMCH, to determine the maximum
      tolerable dose (MTD) for subsequent carcinogenicity study. Mice were randomly
      divided into 5 groups, each consisting of 10 males and 10 females. Eight animals
      of both sexes in the 4.0% TMCH group died during the early administration period.
      Suppression of body weight gains was marked in both sexes of the 4.0% and 2.0%
      TMCH groups as compared with the control group. The mean food consumption in all
      groups treated with TMCH was lower than that in the control group in a dose
      related manner. Hematological examination revealed decreases in the number of
      erythrocytes, volume of hemoglobin, and values for hematocrit and mean
      corpuscular volume (MCV) in both sexes of the 4.0% and 2.0% TMCH groups. The
      relative liver weights of all groups treated with TMCH increased in a dose
      related manner, whereas both absolute and relative spleen weights decreased in a
      dose-dependent manner. Histopathologically, swelling of the hepatocytes was found
      centrilobularly or diffusely in both sexes of the 1.0, 2.0 and 4.0% TMCH groups,
      and decrease of the hematopoietic cells in the bone marrow was observed in both
      sexes of the 2.0 and 4.0% TMCH groups. In addition, atrophy of red pulp and white
      pulp of the spleen was found in both sexes of the 2% and 4% TMCH groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1364436
TI  - [A study of the relationships between exposure periods and no-effect doses in
      repeated dose toxicity tests].
AB  - In the risk assessment of chemicals to humans, it is a very important step to
      determine no-observed-adverse-effect-levels (NOAEL) or lowest-observed-adverse
      effect-levels (LOAEL) from animal experiments. Recently, short-term screening
      tests, such as 28-day repeated dose toxicity test, are carried out in accordance
      with the regulative guidelines for the safety evaluation of chemicals. However,
      many problems still remain in the risk assessment to human based on short-term
      toxicity studies. For this reason, we studied the relationships between the
      exposure periods and NOAELs or LOAELs in repeated dose toxicity tests using
      available test results of 18 halogenated compounds. The ratios between each NOAEL
      or LOAEL of short-term tests (14, 28 days, 13 weeks and 6 month) and those of
      long-term tests (longer than one year) were calculated on the basis of same
      animal species, route and toxic effect. From this study, it was considered that
      exposures above 13 weeks were needed to satisfy the present safety factor
      considerations for setting an acceptable daily intake (ADI).

PMID- 1364437
TI  - [Flower bud differentiation and development of opium poppy (Papaver somniferum
      L.) II. Effects of daylength and temperature].
AB  - We investigated the effect of daylength (from 9 to 15 hours) and cultivation
      temperature (from about 13 to 25 degrees C) on flower bud differentiation of
      three strains of Papaver somniferum L. cv. Ikkanshu, which have been cultivated
      in Nayoro (Hokkaido), Tsukuba (Central Honshu) and Nagasaki (Kyushu) for the last
      a few decades. 1. The experiment on the effect of daylength on flowering revealed
      that the longer the photoperiod was, the earlier flowering occurred. 2. Flower
      bud differentiation was observed at temperatures of 20 degrees C or less but
      never at 25 degrees C, and it was more quickly induced at lower temperatures.
      Furthermore, we also found that the optimum temperature for flower bud
      development following differentiation was 20 degrees C. From these findings, we
      reached the conclusion that this species has thermosensitivity. 3. Flower bud
      differentiation clearly occurred later in the Nayoro strain than in the Nagasaki
      strain or the Tsukuba strain. This seems to indicate that the Nayoro strain is a
      different ecological type from other strains. 4. When we compared the size and
      dry weight of the capsules, which are known to be closely related to opium yield,
      the capsules of the Nagasaki and Tsukuba strains were considerably smaller and
      lighter than those of the Nayoro strain. This is attributable to the fact that
      flower bud differentiation occurred at an early stage before the achievement of
      sufficient vegetative growth in the Nagasaki and Tsukuba strains.

PMID- 1364438
TI  - [Fungi isolated from diseased medicinal plants].
AB  - One hundred and forty-four fungal isolates were obtained from diseased Paeonia
      albiflora Pall. var. trichocarpa Bung., Astragalus membranaceus Bung.,
      Lithospermum erythrorhizon Sieb. et Zucc., Ledebouriella seseloides Wolff and
      Bupleurum falcatum L. which were collected in the test field of Tsukuba Medicinal
      Plant Research Station, National Institute of Hygienic Sciences. Most of them
      were identified into 15 genera containing 8 species. Fungal species presumed to
      be pathogens of the host plants were as follows: Cladosporium paeoniae,
      Pestalotia paeoniicola, Glomerella cingulata, Hainesia lythri, Guignardia sp. and
      Alternaria sp. from P. albiflora, Fusarium spp., Rhizoctonia spp. and
      Neocosmospora vasinfecta from A. membranaceus, Colletotrichum gloeosporioides
      from L. erythrorhizon, Rhizoctonia sp., Fusarium spp., Phoma sp. and Pyrenochaeta
      sp. from L. seseloides, and Fusarium sp., Alternaria alternata, Phyllosticta sp.,
      Phoma sp., Phomopsis sp. and C. gloeosporioides from B. falcatum. Roots of B.
      falcatum were found to be parasitized by Meloidogyne sp.

PMID- 1364439
TI  - [Studies on the identification of psychotropic substances. VIII. Preparation and
      various analytical data of reference standard of some stimulants, amfepramone,
      cathinone, N-ethylamphetamine, fenethylline, fenproporex and mefenorex].
AB  - The Reference Standards for amfepramone, cathinone, N-ethylamphetamine,
      fenethylline, fenproporex and mefenorex were prepared. Their purities determined
      by HPLC were more than 99.5%. For the identification and determination of these
      six drugs, their analytical data were measured and discussed by TLC, UV, IR,
      HPLC, GC/MS and NMR.

PMID- 1364440
TI  - The metabolism of 1,6-dinitropyrene in rat hepatocytes.
AB  - This paper reports investigations using hepatocytes to study the metabolism and
      DNA binding of the environmental contaminant, 1,6-dinitropyrene. Since 1,6
      dinitropyrene is not believed to be mutagenic per se, metabolites were
      synthesized and the metabolism of 1,6-dinitropyrene was subsequently studied in
      rat hepatocytes. The mode of activation of dinitropyrenes is reduction of one of
      the nitro groups. Nitroreduction has been shown previously to be oxygen sensitive
      and therefore the effect of oxygen on the metabolic pattern and DNA binding was
      investigated by comparing results from aerobic and anaerobic conditions. The
      binding of [14C]1,6-dinitropyrene equivalents to rat hepatocyte DNA was increased
      by 15% in the presence of oxygen. Although there was little difference in the
      rate of 1,6-dinitropyrene metabolism, with or without O2, there was a difference
      in the metabolic pattern. Under anaerobic conditions there was an increase in the
      level of the terminal reduction product 1-amino-6-nitropyrene.

PMID- 1364441
TI  - [Preparation of the first draft of environmental health criteria for
      acetonitrile: production process of the draft].
AB  - Acetonitrile is a high-polarity aprotic organic solvent used in DNA synthesizers,
      HPLC, and electrochemistry. In addition, it is used larger amounts at
      petrochemical companies and pharmaceutical firms. Preparation of an Environmental
      Health Criteria (EHC) monograph for acetonitrile was started in 1986, and its
      first draft except the environmental section was completed on June 21, 1991. The
      environmental section has been prepared by Dr. S. Dobson (ITE/UK). The first
      draft was circulated to EHC Contact Points for comment in March 1992.

PMID- 1364442
TI  - [Determination of nicarbazin in imported chicken].
AB  - The confirmation and quantitative analysis of nicarbazin (NCZ) in imported
      chickens were made by high performance liquid chromatography equipped with a
      photodiode array detector. The results showed that 1 out of 7 chicken samples
      contained over 30 ng/g of NCZ. The concentrations of NCZ varied from 10 to 120
      ng/g according to the parts of the NCZ positive chicken samples.

PMID- 1364443
TI  - [Food hygienic indexes on biodegradable polymers].
AB  - Current specifications for food packaging made of polyolefine plastics were
      applied to biodegradable plastics. No lead and cadmium were detected in any
      biodegradable plastic samples with the exception of bacterial cellulose, which
      contained trace amounts of lead and cadmium. Potassium permanganate consumption
      amount was less than the current specification level for polyofines. Sugars
      leached from bacterial cellulose was 22 +/- 1 microgram per 100 cm2 as glucose,
      and amino acids leached from poly-gamma-methylglutamate films was 8 +/- 3
      micrograms per 100 cm2 as glutamic acid.

PMID- 1364444
TI  - [Migration test of lead and cadmium from plastic wares in contact with food].
AB  - Release of lead and cadmium from plastic tableware was examined. Samples were
      treated with 2 ml of 4% acetic acid or 0.1N HCl per cm2 of the surface area at 60
      degrees C or 95 degrees C for 30 min. No migration of lead and cadmium from
      samples containing up to 391 ppm lead or 6863 ppm cadmium was observed.

PMID- 1364445
TI  - [Determination of volatile substances and leachable components in polystyrene
      food contact wares].
AB  - Material and migration tests of food-contact plastic wares made of polystyrene
      were carried out. The average concentration of volatile substances (sum of
      toluene, ethylbenzene, isopropylbenzene, n -propylbenzene, and styrene) in
      materials was 861 +/- 692 ppm. Styrene was observed in 95% of 19 samples. alpha
      Methylstyrene, which is one of the material compounds of polystyrene, was
      detected in one sample. Release of volatile substances into n-heptane was not
      observed at the detection limits of 0.1 ppm.

PMID- 1364446
TI  - [Preliminary screening for antiviral AIDS drugs. III. Report on fiscal year
      1990].
AB  - Preliminary screening for antiviral AIDS drugs has been carried out using three
      different in vitro assay systems. Among 106 samples tested, five were found to
      inhibit the growth of HIV in vitro. Two of five have a hopeful sign, as the range
      of effective doses of the samples is wide.

PMID- 1364447
TI  - [First drafts of environmental health criteria circulated for comments by IPCS in
      1991-1992].
AB  - Summaries of first drafts of Environmental Health Criteria (EHC), which were
      circulated for comments by IPCS in the period of 1991-1992, were presented. EHC
      drafts on 14 compounds and one methodology were received in this period.

PMID- 1364448
TI  - [Problems and their solutions in preparation of environmental health criteria
      documents of IPCS].
AB  - Problems and solutions in preparing Environmental Health Criteria (EHC) documents
      for IPCS (International Programme on Chemical Safety) are summarized. Selection
      of target chemicals, information search, appointment of appropriate drafters,
      selection and evaluation of data, use of proprietary data, scientific and English
      editing, organization of international expert meetings, coordination and
      secretarial works were the important factors in the preparation of EHCs. The
      elucidation of the process of risk assessment of chemicals in the EHC preparation
      will be helpful in preparing other criteria documents.

PMID- 1364449
TI  - [Tension neck].

PMID- 1364450
TI  - [Man and nature in the stream of history].

PMID- 1364451
TI  - [Seasonal affective disorder].

PMID- 1364452
TI  - [The boundaries of treatment].

PMID- 1364453
TI  - [The fibrotic diseases of the skin].

PMID- 1364454
TI  - [The changing role of radiation therapy in the treatment of bladder carcinoma].

PMID- 1364455
TI  - [The evaluation of physical activity and energy consumption].

PMID- 1364456
TI  - [Should brain metastases be operated on?].

PMID- 1364457
TI  - [Heart infarction and thrombosis in the left ventricle].

PMID- 1364458
TI  - [Can alcohol induced liver disease be an indication for liver transplantation?].

PMID- 1364459
TI  - [Burch's operation--an efficient treatment for stress urinary incontinence in
      women].

PMID- 1364460
TI  - [Design of forms from the aspect of computerized data storage and statistical
      analysis].

PMID- 1364461
TI  - [Evaluation of immune deficiency].

PMID- 1364462
TI  - [Daily fluctuation in the concentration of serum thyrotropin and the
      interpretation of results].

PMID- 1364463
TI  - [Inefficient ventilation of lungs associated with chronic heart failure--partial
      reason for shortness of breath during stress?].

PMID- 1364464
TI  - [What's new in the genetics of familial colon cancer?].

PMID- 1364465
TI  - [Chronic meningococcemia--a rare prolonged infection and disturbance in the
      function of complement].

PMID- 1364466
TI  - [Treatment of menorrhagia].

PMID- 1364467
TI  - [Schizophrenia--vanishing part of cultural heritage?].

PMID- 1364468
TI  - [Differential diagnosis in nephropathia epidemica: nephrography or virus
      serology?].

PMID- 1364469
TI  - [Study of the effects of some prophylactic measures and radiological
      contamination in Poland after the Czernobyl accident; Introduction to the
      research program MZ-XVII].
AB  - An aim of the introduction is to remained the scale of radiological contamination
      in Poland after the accident in the Czernobyl Power Station, the evaluation of
      findings which led to prophylactic administration of potassium iodide first in
      part of Poland and later Country-wide. The introduction gives also the history of
      Research Programme MZ-XVII and its implementation in several regions of Poland.
      The main aims of the Programme were: 1. Estimation of radioiodine dose
      accumulated in thyroids of children, youths and adults who lived in different
      parts of Poland and evaluation whether these doses could lead to the development
      of thyroid disorders. 2. Evaluation of thyroid function in those exposed to
      radioiodine in different trimesters of preneonatal life, who were born euthyroid
      and who were given potassium iodine in first days of life. 3. Evaluation of
      efficacy of single dose of potassium iodide and estimation of possible
      intrathyroid and extrathyroid side-effects after prophylactic iodide
      administration. The foundations of the Programme and Centers involved in its
      implementation are also specified.

PMID- 1364470
TI  - [Epidemiologic foundation for population studies of program MZ-XVII].
AB  - Epidemiological foundation included: aim of studies, knowledge about epidemiology
      of thyroid disorders in Poland, evaluation of radioiodine dose accumulated in
      thyroids of inhabitants of different age living in different par of Poland,
      information about relative diet iodine deficiency in different parts of Poland
      and identification of research teams (manpower) capable to carry on population
      studies. The final identification of epidemiological foundation was proceeded by
      pilot studies performed in 4 different regions of Poland. Finally it was decided
      that population studies would be performed in so called Regions of 6 different
      University Medical Schools (Bialystok, Krakow, Lodz, Poznan, Szczecin, Wroclaw).
      The sample will be selected randomly on the base of information from the voting
      lists (random selection of vovoidoship, then towns and villages, then streets and
      number of houses, then number of flats. All living in selected flat or house
      during Czernobyl accident and born between January 1974 and December 1985
      (children) and between January 1926 and December 1973 (adults) will be considered
      "the sample". In all cases the sample will be examined by means of unified
      questionnaire and protocol of medical and laboratory examination. The same kits
      (of the same producers) will be used to evaluate serum TSH, T4, T3 and thyroid
      autoantibodies. The data obtained will be evaluated by unified computerized
      system. Separate studies involved the sample of newborns exposed to radioiodine
      during last trimester of pregnancy, found to be euthyroid and given potassium
      iodide in first days of life. Separate system was also used to investigate effect
      of radioiodine and of prophylactic dose of potassium iodide in those with past
      history of thyroid disorders.

PMID- 1364471
TI  - [An information system for analyzing the need for examining certain aspects of
      radiologic contamination caused by the Czernobyl catastrophe].
AB  - In this paper we briefly report a set of programming tools designed to support
      the analysis of some aspects of radiological contamination caused by Tchernobyl
      catastrophe. First of all a system for data storing is characterized; after
      mentioning basic data structures, two mutations of this system are described (one
      version for data collected during a pilot study and the second for the main
      investigation). Next the problems of data analysis are discussed. Again we
      distinguish between pilot and main analysis. A simple query language is
      introduced and the procedures for coding some variables are mentioned. Lastly the
      problems and difficulties arising during the whole analysis are specified.

PMID- 1364472
TI  - [Evaluation of equivalent body burden in the thyroid for the people of Poland on
      results of 131I absorption after the disaster in Czernobyl. Determination of
      thyroid blockade with potassium iodide].
AB  - An assessment of effectiveness of the administering of single dose of stable
      iodine in Poland on the reduction of 131I doses in thyroid has been performed. 5
      compartment model of metabolism of iodine developed by Johnson has been used to
      evaluate predicted levels of stable iodine and 131I content in thyroid and
      commitment dose equivalent H50 for different doses of stable iodine and various
      age and sex group population. The measured values of 131I concentration in air
      and in milk and standard values for milk and food consumption and inhalation rate
      as well as metabolic parameters were used. Theoretical calculations showed that
      administering of stable iodine on 1986-04-28, 1986-04-29, 1986-04-30 and 1986-05
      01 could have reduced committed dose equivalent H50 form ingestion with
      inhalation pathway by about 44%, 40%, 26%, 12% respectively. On the basis of
      measured 131I activity in the thyroid for inhabitants from different districts in
      Poland (1400 measurement) committed dose equivalents were determined and analysis
      of radiation hazard from 131I were performed. In the most contaminated regions of
      Poland average H50 doses for children 1-5 and 5-10 years old are close to 50 mSv
      (permissible level for population) and maximal doses exceed this limit four
      times. These maximal doses occurred for about from 5% inhabitants from these
      area. In the moderate and low contaminated regions of Poland the average doses
      are fivefold and tenfold less respectively.

PMID- 1364473
TI  - [Chronicled report on the period from May 1 to September 27, 1989. Discussion of
      risk factors].
AB  - The Institute of Mother and Child was invited in 1988 by professor J. Nauman to
      his Chernobyl program, so as to inspect children born after Chernobyl accident,
      particularly these born in first days following the accident dated 26 april 1986.
      The central part of Poland is covered with screening for congenital PKU and
      hypothyroidism therefore all children had estimated TSH-spot levels between 3rd
      and 5th day of life. So as to control the present state of general health and
      thyroid state in the study group a questionnaire with a letter to parents
      explaining the aim of the inquiry was sent to the parents (see addenda). About
      14000 letters were send from which around 12000 responses were returned to the
      Institute. From informations received this way we draw the preliminary conclusion
      that no significant damage in health of these children or their siblings can be
      found. About 20% of the mothers admitted taking the Lugol solution in a last day
      of pregnancy. However it should be taken into account that these data were
      collected 2 years after the accident and are not fully reliable. In the period
      1989-1990 a group of 1912 children (938 boys and 974 girls) was called to the
      Department of Endocrinology of the Institute and inspected. The age was from 2.9
      to 4.2 years. All children had screening TSH-spot test result negative (below 30
      microIU/ml). General health state The general health state of the children
      inspected was good. Only 33 of them (1.7%) had various congenital malformations
      what is not different from general population of polish children. Mental
      development was in 1897 cases normal, in 15 cases IQ was decreased and the score
      varied from 75 to 80 according the Brunet-Lezine scale. Average physical
      development was normal. Body height evaluated in standard deviation score (SDS)
      was as follows: SDS = 0.0 in 359; SDS = +0.9 +/- 0.6 in 906 and SDS = -0.5 +/-
      0.3 in 647 cases. Thyroid state At 1904 inspected and analytically estimated
      children the thyroid function was normal. Only in 8 cases (0.8%) a goiter was
      found with euthyroid state. Analytical data were as follows: total T4 serum level
      = 111.8 + 43.1 nmol/l (50.4-171.9), ref. value: 50.1-170.0 nmol/l; total T3 serum
      level = 2.5 +/- 0.4 nmol/l (ref. value 1.9-3.6); TSH serum level 4.4 +/- 2.6
      uIU/ml. Trace amounts of antithyroid membrane antibodies were found at 12
      children (0.63%) of the group in serum diluted 1:250.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1364474
TI  - [Results of studies on the effect of radiologic contamination after the Czernobyl
      catastrophe and prophylactic iodine on thyroid morphology and function of
      inhabitants of North-East Poland].
AB  - The results of the investigations of radioactive contamination after the
      Chernobyl catastrophe and subsequent iodine prophylaxis on the thyroid gland
      function and morphology in Northeast Poland. The aim of the study was to
      determine whether kalium iodine in one dose during radioactive contamination in
      Poland limited the radioactive dose in the thyroid gland and if significant
      disadvantageous side-effects in the intrathyroid and extrathyroid occurred.
      Additionally during the studies we tried to determine if radioactive iodine
      contamination which occurred in the region of the Medical Academy in Bialystok
      caused an increase in thyroid disease. It is interesting to note the different
      results obtained after radioactive contamination with the results from the
      investigations in this same territory in 1983-1985. In 1983-1985, before the
      Chernobyl catastrophe, 6,921 persons in Northeast Poland were investigated. In
      1986-1988, immediately after the disaster 4,010 persons were investigated. The
      main study according to grant No MZ-XVII was carried out in three provinces:
      Bialystok, Suwalki and Olsztyn. In this investigation 10,011 persons born before
      April 26, 1986 and after January 1, 1936 participated, 5,789 townspeople and
      4,222 villagers, 3,987 children up to 16 years of age it the time of the disaster
      1,973 boys and 2,009 girls; 6,024 adults 2,509 men and 3,516 women were drawn
      from a register. Committed doses to the thyroid in the investigated region were
      one of the highest in Poland and depended on age group and were depended on time
      of prophylaxis non proportional. Iodine prophylaxis was provided mainly with one
      dose of Lugol solution about 90%, 95% children and 30% adults took iodine. The
      majority of the population (53.3%-74%) were given iodine in April. From May 1st
      to 5th 23.0-43.4% received iodine, but after May 5th very few persons. Iodine was
      well tolerated, but Lugol Solution was better tolerated than other kinds of
      iodine. Only 241 (4.4%) cases had side effects, mainly vomiting (143), symptoms
      such as stomach ache, diarrhea, dyspnoe, skinrash etc. in lesser numbers. 12% (29
      persons) were seen by a physician. In the investigated population were 200
      pregnant women aged 19-40 years of which the majority (177) delivered full term
      healthy babies. Only 1 interrupted pregnancy and 7 had spontaneous abortion.
      Changes in the thyroid were noticed by 187 persons (2.3%-11.7%) most of which
      were enlargement of the thyroid, but only a few were confirmed by a physician. In
      the studied population from 1989 to 1990 over 30% of the population had
      struma.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1364475
TI  - [Study on consequences of radioactive iodine pollution and iodine prophylaxis
      after the Czernobyl accident in the Krakow region].
AB  - Program of investigations of effects of radiation and iodine prophylaxis
      undertaken after Czarnobyl accident in Krakow region had to be modified due to
      goiter endemy in this region. These modifications included: 1) Division of the
      region into 3 areas (voivodship Nowy Sacz, urban voivodship Krakow and area of
      Kielce and Swietokrzyskie mountains). 2) Study on iodine uptake in food and
      urinary secretion. 3) Examination of iodine level in drinking water, add an
      attempt of calculation of radiation dose absorbed by thyroid. Characterization of
      selected areas, principles of selection of study groups are presented as well as
      organizational details and methods of data collection.

PMID- 1364476
TI  - [Evaluation of iodine levels in daily dietary intake and urine of persons
      participating in epidemiological studies in the Krakow macro-region after the
      disaster in Czernobyl and level of iodine in drinking water of that region].
AB  - Following the Czernobyl accident, an epidemiologic study was undertaken in which
      the daily iodine intake was estimated in 15% of the population studied. Iodine
      excretion was measured in single morning urine specimens. The iodine content was
      also assessed in the water form wells and in cow-milk at farms in randomly chosen
      villages in the region of Krynica and Nowy Sacz. On the basis of a 24-hour diet
      recall, the mass of each food product consumed daily was estimated for 483
      persons in the Krakow voivodship (14.4% of the total population) and for 397
      persons in the Nowy Sacz voivodship (15.8% of the total population). Using this
      data, the nutrient content of the daily diet was calculated for each studied
      individual. Measurements of iodine content in water and cow-milk show relatively
      lower iodine levels in the Nowy Sacz voivodship. The estimated value of the
      iodine content in milk (5.5 micrograms/100 g of milk) was considered in the
      estimates of the chemical composition of the daily diet of the inhabitants of
      this region. The mean values of the daily energy as well as the protein and
      calcium consumption in all subpopulations grouped with respect to domicile, age
      and sex, fell within the recommended daily allowances for these groups. The
      iodine content, while widely scattered, concentrated around low values. The
      median values of the iodine content in children of age 3-10 years, age 10-16
      years and in adults, were 66%, 48% and 25-40% of the recommended daily
      allowances, respectively. No particular differences in the food intakes were
      observed between inhabitants of Krakow and Nowy Sacz voivodships. Nor were
      significant differences found in the urine iodine excretion in groups of these
      regions. The low iodine content in the daily food intake may be an essential
      factor in the ethiology of the increasing number of thyroid goiter.

PMID- 1364477
TI  - [Epidemiologic studies after the disaster in Czernobyl in the population of
      children in the Krakow region].
AB  - In 1989-1990 the epidemiologic studies about the impact of of Czarnobyl events on
      the health of children in Krakow and Nowy Sacz region were performed. The
      morphologic and functional changes of thyroid gland in children were estimated.
      Almost 90% of children in both districts received the iodine preparations for
      prophylactic reason. The mean time of intake was between 5-10 days following the
      Czarnobyl explosion. There were no relationship between the dose of iodine
      absorbed during prophylactic action and incidence of goiter. The prevalence of
      goiter amounted to 34.8-47.6% in boys and girls consecutively in Krakow district
      and 53.8-70.5% in Nowy Sacz. No hormonal changes in T3, T4 and TSH serum
      concentration were found in children with goiter and those without goiter. The
      complications after iodine intake were transient and seen only in a small number
      of children.

PMID- 1364478
TI  - [Results of epidemiologic studies performed after the disaster in Czernobyl among
      the adult part of the population in the region of Krakow].
AB  - Epidemiologic studies following the Czernobyl accident were performed in region
      Krakow, including Krakow, Nowy Sacz and Kielce district. 1426 males and 2495
      females were selected according to the random sample on the whole population of
      Krakow and Nowy Sacz, as well as in some selected areas in Swietokrzyski
      Mountains, and in Kielcecity. The aim of the study was to assess the results of
      the prophylaxis with Kalium iodine after the radiation and the incidence of the
      goiter in the population. It was stated, that 19.2% of the population in Krakow
      district, 16.9% in Nowy Sacz and 20% in Kielce received the prophylactic dosis of
      K.J. 80% took mainly the Lugol solution, between May, the 1st and 5th, 1986.
      Among 18 of person showing side effects like gastrointestinal disturbances, 16
      were of female sex. Goiter incidence according to WHO classification was 50.7%,
      67.3% and 49.9% in Krakow, Nowy Sacz and Kielce respectively. The difference
      between the incidence of goiter in males and females was 1:3. In women it was
      rather Ist and IInd degree of goiter, in men OB and Ist. Nodules of thyroid gland
      in the rural region of Krakow, Nowy Sacz and Kielce were seen in women in 10.8%,
      1.7%, add 12.3% consecutively. Hormonal studies i.e T3, T4, TSH serum
      concentration showed normal results in all groups studied. TSH concentration was
      the highest in the group OB. The microsomal and antithyroglobulin antibodies
      level was the same independently on the prophylactic dosis of Lugol solution. The
      high incidence of thyroid diseases not related to the accident was
      observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364479
TI  - [Influence of radioactive contamination and iodine prophylaxis after the
      Czernobyl disaster on thyroid morphology and function of the Poznan region].
AB  - The radioactive contamination of Poznan Region was recognized after Chernobyl
      accident as average. The predicted values of minimal (inhalation) and maximal
      (inhalation and ingestion) committed dose equivalent to the thyroid varied from
      2.5 (min) to 24.7 (max) mSv in different groups of adults and children. To follow
      up the results of iodine prophylaxis and some aspects of possible thyroid gland
      morphological and functional changes 11086 persons were carefully investigated
      clinically and biochemically. Among these 11086 persons were 42.6% males and
      57.4% females both adults from 17 till 40 year and children up do 16 years. The
      following parameters were reviewed: pregnancy, time of residence in the region,
      thyroid abnormalities, family history concerning thyroid diseases, iodine intake
      in April and May 1986 with possible side effects, changes in the thyroid size
      observed before and after 1986, degree and kind of thyroid enlargement, serum
      concentration of T3, T4, TSH, ATMA and ATG titre and finally the effectiveness of
      thyroid blockade at 24, 48 and 72 h after ingestion of Lugol's solution. Side
      effects of the ingestion of potassium iodide from 30-70 mg were observed in 153
      cases, 36 of them consulted medical doctors but in no case the side effects
      (dominated by vomiting) threatened the life. In the investigated group were 144
      pregnant women. Majority, because 88% of them delivered the baby on or after time
      and 6.9% before time, 4.9% of natural abortions were noted but non artificial. In
      the group of children thyroid gland abnormalities before 1986 were reported in 3
      cases in 23 after 1986 it is after Chernobyl accident. This information is
      interesting but needs more precise analysis of different dependencies occurring.
      The data obtained indicated the existence in Poznan. Region the goiter endemy
      because 27.5% of investigated children and adults had goiter classified as grades
      O-B, I, II and III. The elevation or diminution of T3 values were noted in 1164
      cases, for T4 in 418 cases and for TSH in 1412 cases. The presence of
      antimembrane and antithyroglobulin antibodies were observed in 303 cases. All
      persons with changes observed in thyroid morphology and function are periodically
      controlled and the results will be published separately. The investigations
      performed and results presented concern the early aspects of radioactive
      contamination and effects of iodine prophylaxis. The answer regarding late
      effects including thyroid cancer needs further multi year studies for which the
      clinical material investigated in different parts of Poland and well documented
      should be used as model group for further periodical studies.

PMID- 1364480
TI  - [Effectiveness of iodine prophylaxis and frequency of thyroid enlargement
      (thyroid goiter) and clinical diagnosis of thyroid diseases in inhabitants of the
      Szczecin region after the Czernobyl accident].
AB  - The study, supported by program MZ-XVII, was carried on 4567 inhabitants of the
      area of Szczecin (2350 females and 2217 males). The population was chosen
      randomly, according to a simple drawing scheme. All subjects were clinically
      examined using standardised questionnaires. In 3468 persons (including 1807 girls
      and women, 1661 boys and men) apart form clinical examination, the assessment of
      thyrotropin, thyroxine and triiodothyronine in serum and frequency of
      antithyroglobulin antibodies and antithyroid membrane antibodies were evaluated.
      The data indicate that 94% of children in Szczecin's region received the
      prophylactic dose of iodine, mostly between the 1st and the 5th of May 1986. Only
      17% of the adults received iodine. The most common preparation was Lugol solution
      given in a single dose. Among all persons who received iodine, only in 5% of
      subjects the side effects were noted (mostly in children), including symptoms of
      gastrointestinal tract (vomiting, abdomen pain) and occasionally intrathyroid
      side effects (thyroid pains). In examined population the high frequency of
      thyroid enlargement, mainly in women (up to 43-44% at the age group 30-50 years)
      was found. The frequency of clinical diagnosis of thyroid disease was higher in
      women than in man (most often the diffuse goiter, rarely the nodular goiter). The
      frequency of thyroid enlargement and clinical diagnosis of thyroid disease was
      not dependent on prophylactic iodine intake. The iodine prophylaxis did not
      influence on thyroid hormones and TSH serum levels and on frequency of
      antithyroid antibodies.

PMID- 1364481
TI  - [Data from the Wroclaw region about thyroid diseases and use of prophylactic
      iodine after the reactor accident in Czernobyl].
AB  - The radiological contamination of Wroclaw Region after Czernobyl accident was
      evaluated as moderate. In the frame of Research Programme MZ-XVII 4310 persons
      (2012 men and 2298 women) were randomly selected and investigated. Among them
      were 1525 children up to 16 years old. 925 children and 854 adults took potassium
      iodide; only minority in April but majority between May 1st and May 5th. Side
      effects was rare phenomenon seen in about 5% of those who ingested potassium
      iodide and in majority of cases was very mild (with rash and vomiting as most
      common clinical symptoms). Only 13 persons with side effects have visited
      physicians. Among 955 women aged 19-40 years 71 were pregnant in May 1986. 55 of
      them delivered on time, 3 before time. Average health state of newborns was 9.1
      according to Apgar scale. 10 women have had spontaneous abortion and 3 decided to
      terminate pregnancy in first 6 weeks. The physical examination revealed the
      presence of diffuse goiter in 384 persons and of nodular goiter in 23 persons. In
      majority of cases the goiter was small, OB or I. according to WHO classification.

PMID- 1364482
TI  - [Effects of prophylactic doses of potassium iodide on the course of thyroid
      diseases (1986-1990) diagnosed due to the atomic accident at Czernobyl in adult
      patients at the outpatient endocrinologic hospital clinic in Lodz].
AB  - 2521 patients of the Lodz Outpatient Endocrinological Clinic (2290 females, 231
      males; inhabitants of the central region of Poland Lodz City, Lodz Metropolitan
      Area, Piotrkow, Plock, Sieradz, Skierniewice and Wloclawek Provinces in which
      committed dose equivalent to the thyroid was between 2.7-7.0 mSv [min.-max.] in
      Skierniewice Province and 4.6-11.7 mSv in Plock Province) were included in the
      study. The patients were divided into 5 groups: I--persons who did not take the
      protective dose of potassium iodide (KI) after Chernobyl Nuclear Power Plant
      accident and did not received any treatment with thyroid preparations or hormones
      at that time (n = 1282), II--patients who receive KI, once or several times (n =
      774), III--patients who took orally iodine tincture or other iodine-containing
      preparations for the above purposes (n-37), IV--patients who took tablets of
      Thyroideum (Polfa) Thyroideum siccum (dry thyroid extract), once or several
      times, as a prophylactic action (n = 79), V--patients who were in the course of
      continuous treatment with Thyreoideum or thyroid hormones at the time of
      Chernobyl accident (n = 349). The analysis was performed for all the patients
      jointly, as well as separately for: either sex, three age groups (18-30, 31-55,
      56-70 yrs) and 7 administrative areas specified above. All the patients were
      subjected into complex clinical examination, serum TSH, T3, T4 concentrations,
      anti-thyroid membrane antibodies (ATMA) and antithyroglobulin antibodies (ATg)
      titres, as well as ultrasound, scintigraphy, and fine needle aspiration biopsy of
      the thyroid (the last two according to indications) included. The patients were
      also examined by means of a special questionnaire (Patient's Inquiry Sheet),
      which was subsequently submitted to computer analysis. All the doctors' diagnoses
      from 1986 (17 different diagnoses) and 1990 (27 different diagnoses), as well as
      the course of diseases, were verified with use of a specially prepared IBM PC/AT
      computer program ChernStat.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1364483
TI  - [Laboratory tests: level of T3, T4, TSH and antithyroid gland autoantibodies in
      the Polish population].
AB  - In 1986-1990 epidemiologic studies on the thyroid diseases frequency in the
      polish population were undertaken. During this studies the serum levels of TSH,
      T4, T3 and autoantibodies were estimated in more than 30 thousand people. TSH was
      estimated in 30749, T4 in 30928, T3 in 30621 and autoantibodies in 31265 randomly
      chosen people in 5 districts. We have arbitrarily established the normal range
      for TSH to be between 0.4-3.8 microIU/ml, for T4 4.4-12.5 micrograms% and for T3
      0.9-1.95 ng/ml. The tested group has been divide in 4 subgroup: girls and boys
      from 1 to 15 years of age the year of the Chernobyl accident, men and women from
      15 to 50 years of age at the date of the accident. TSH values in the normal range
      were found in 85 to 92% of the tested population, depending on the subgroup. T4
      vales in the normal range were found in 85 to 92% of the tested groups. T3 vales
      in the normal range were found in 86 to 93% of the tested groups. The absence of
      any kind of autoantibodies was established in 89.7% of the tested population. TSH
      values was above the normal range (above 3.8 microIU/ml) in 3.4% of boys, 4.3%
      girls, 3.2% men and 3.8% women. TSH vales below the normal range (less the 0.4
      microIU/ml) were found in 4.3% boys, 5.0% girls, 10% men and 11.2% women. T4
      values above the normal range (higher then 12.5 micrograms%) were found in 12.9%
      boys, 12.6% girls, 4.6% men and 5.9% women.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364484
TI  - [Results of studies performed with the MZ-XVII program on a national scale;
      summary and conclusions].
AB  - MOST IMPORTANT OBSERVATIONS: (FROM COUNTRY-WIDE POPULATION STUDIES) 1. In some
      voivodships localized in south-east and north-east parts of Poland thyroids of
      young children would, without protective measures, accumulate more then 60 MsV of
      radioiodine, thus exceeding intervention level settled for the country. 2.
      Thyroid function of newborns exposed to radioiodine during neonatal life was
      normal and frequency of neonatal hypothyroidism similar to that seen in years
      before Czernobyl accident. 3. Potassium iodide administrated to newborns in some
      of them profuced transient rise of TSH (Wolff-Chaikoff phenomenon), thus
      suggesting, that ki dose settled for newborns could be to high. 4. Thyroid
      radioiodine dose accumulated in thyroids of older children, teenagers and adults
      was in majority of regions well below the dose of 50 MsV. 5. The frequency of non
      toxic diffuse goiter, especially in traditional endemic goiter area was found to
      be high, but is also relatively high in others regions of Poland and seems to
      depend on iodine deficiency or relative iodine deficiency. 6. The frequency of
      other thyroid disorders is within the limit reported in countries with relative
      iodine deficiency. 7. More than 95% of children and teenagers took protective,
      single dose of potassium iodide (about 10 millions). 8. Approximately 27% of
      adults took protective dose of potassium iodide (about 7 millions). 9.
      Organization of protective action in 11 north-east and south-east voivodoships
      was good about 75% of all obtain ki solution within 24 hours. In the rest of the
      country where protective action was ordered april 30, in afternoon hrs only about
      25% obtained ki the same day and the rest during next 48-72 hrs. 10. The fact
      that prior to the protective action limited number of children was given iodine
      alcohol solution permitted for external use speaks about the fear and panic
      observed in Poland in first days after Czernobyl accident. 11. Extrathyroidal
      side-effects after ki administration appeared in about 5% were usually light or
      moderate and in majority of cases disappearing without medical assistance.
      Vomiting was most commonly seen side-effect in young children, thus suggesting
      that either dose, or the chemical form of the drug for this group of age was
      unproper. 12. Intrathyroidal side-effects of single dose of ki was rare
      phenomenon seen mostly in newborns, very young children and some adults with
      history of thyroid disease in the past. 13. Its possible that even small dose of
      radioiodine accumulated in thyroid produce immunological response leading to the
      appearance of thyroid antibodies in blood serum.

PMID- 1364485
TI  - [Endemic state of goiter and prophylactic iodine in Poland and Europe].

PMID- 1364486
TI  - [Analysis of early results of combined treatment with glucocorticoids and
      telecobalt therapy for Graves' disease ophthalmopathy].
AB  - Early results of combined use of glucocorticoid administration and irradiation
      with radioactive cobalt for treatment of oedematous-infiltrative ophthalmopathy
      associated with Graves' disease have been analyzed in a group of 33 patients
      including 28 women and 5 men of age between 25 and 66 years (mean age 47.3
      years). The combined therapy was a modification of the original method of
      Bartalena et al. which consisted in the gradual increase of the initial dose of
      glucocorticoids and prolongation of the period of administration of the drug. The
      ophthalmic lesions were assessed by thorough ophthalmologic examination and
      classified according to Werner. The ophthalmopathy index was calculated according
      to Donaldson. Satisfactory results of treatment have been obtained in 32
      patients, with 9 patients being completely relieved from any objective or
      subjective ophthalmic symptoms (very good results), and 23 patients having still
      small afflictions originating from the soft tissues of the eye socket,
      exophthalmos, diplopia during marginal vision and a decreased visual acuity (good
      results). The clinical recovery was mostly connected with the improvement in the
      condition of soft tissues of the eye socket, cornea and external ocular muscles
      and, to a smaller extent, exophthalmos which persisted to some degree and acuity
      of vision not always attaining normal values. In one person the results of
      treatment were unsatisfactory despite some improvement. Very good and good
      results obtained in 97% of patients indicate that the administration of
      glucocorticoids combined with the irradiation of retrobulbar tissues with
      radioactive cobalt can now be regarded as the most effective method of treatment
      of the progressive oedematous-infiltrative ophthalmopathy.

PMID- 1364487
TI  - Changes in serum T4, T3 and TSH concentrations in newborns and infants with
      congenital goiter from the Mazovia region.
AB  - Thyroid function was investigated in a group of 61 newborns with congenital
      goiter before starting the therapy with thyroid hormones. The group included 19
      girls and 42 boys, of which 27 were of age not exceeding one week (group I), 19
      were between the first and the second week (group II), and 15 were between the
      second week and the third month of life (group III). The concentrations of the
      thyroid hormones were determined by radioimmunoassay. The values obtained have
      been compared with the local reference range obtained for the newborns of the
      Mazovia region. The values remaining outside the reference range were found in
      47.5% of the newborns studied. The elevated values of TSH were observed mainly in
      group I newborns (12 from 27); among group II newborns there was only one with
      the elevated values, and none among the newborns of group III. thyroxine (T4)
      values were lowered in 14 among 27 newborns of group I, and in 2 among 19
      newborns of group II; all T4 values were normal in group III. The percentage of
      the elevated values of triiodothyronine (T3) was higher in older newborns (group
      III). The elevated level of T3 accompanied by the lowered level of T4 with the
      normal or moderately elevated level of TSH is characteristic for the adaptation
      to the deficiency of iodine. There is preferential secretion of T3 aimed at
      maintaining euthyreosis. The elevated levels of T3 found in 30% of newborns with
      untreated goiter suggest an intrauterine deficit of iodine as a cause of the
      goiter appearance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364488
TI  - [Migration inhibition test with thyroid membrane antigen in Graves-Basedow
      disease and nodular goiter].
AB  - The evaluation of the migration inhibition test with thyroid membrane antigen was
      carried out in 20 patients with Graves' disease, 13 patients with neutral nodular
      goiter and 13 healthy subjects. A significant inhibition of migration by thyroid
      antigen as compared to the control group was demonstrated only in the patients
      with Graves' disease (the value of the migration index was 0.57 +/- 0.07). The
      respective value was 0.79 +/- 0.16 in patients with nodular goiter and 0.85 +/-
      0.11 in healthy subjects. The results obtained indicate the practical value of
      the migration inhibition test in diagnosing the thyroid diseases having an
      autoimmune background.

PMID- 1364489
TI  - [Association of primary autoimmune hypothyroidism with Addison's anemia].
AB  - Intestinal absorption of vitamin B12 as measured by the Schillin test was studied
      in 50 patients with primary hypothyroidism of autoimmune origin. The impaired
      absorption of vitamin B12 was found in 24% of the patients studied, and in 6% a
      clinically evident form of pernicious anemia was diagnosed. The patients with
      hypothyroidism and simultaneous defect in absorption of vitamin B12 were
      characterized by more frequent occurrence of the high titer of antithyroid
      microsomal antibodies, higher blood serum concentration of TSH and lower blood
      content of hemoglobin as compared with hypothyroid patients having normal
      intestinal absorption of vitamin B12.

PMID- 1364490
TI  - [Behavior of thyrotropic, triiodothyronine, thyroxine and cortisol hormone levels
      in blood serum of patients with duodenal ulcer treated with ranitidine].
AB  - Blood serum concentrations of thyrotropic hormone (TSH), triiodothyronine (T3),
      thyroxine (T4) and cortisol have been measured in 50 patients with duodenal
      ulcer. The determinations were repeated after a specific time of treatment with
      ranitidine: in 45 patients after 3 weeks and in 37 after additional 30 days of
      treatment. During the first period of treatment ranitidine was administered at a
      dose of 300 mg divided into two daily doses and during the second period of
      treatment at a single daily dose of 150 mg. A small but statistically significant
      changes, an increase in T3 and a decrease in TSH concentration, were observed
      before the treatment. No changes concerning these two parameters were found as an
      effect of the treatment. A decrease in the concentration of T4 was found, on the
      other hand, after three weeks of ranitidine administration. This decrease
      persisted after further 30 days of chronic treatment with ranitidine. No
      significant changes concerning blood serum cortisol concentration were found in
      any of the studied groups.

PMID- 1364491
TI  - [Effect of nifedipine treatment on the renin-aldosterone system and secretion of
      cortisol and growth hormone in patients with essential hypertension].
AB  - The effect of treatment of hypertension with nifedipine on plasma renin activity,
      blood serum level of aldosterone in the course of renin test, and cortisol and
      growth hormone concentrations after stimulation with insulin hypoglycemia was
      followed during two weeks of treatment in 40 patients with essential
      hypertension. No significant differences in the secretion of the hormones
      studied, as compared to the patients with the normal arterial blood pressure,
      were found. After nifedipine treatment no significant changes in the secretion of
      aldosterone, cortisol and growth hormone were observed despite a significant fall
      in the arterial blood pressure while there was a moderate stimulatory effect on
      renin secretion. The results obtained indicate that nifedipine has only small
      effect on the hormonal system of patients with essential hypertension.

PMID- 1364492
TI  - [Level of estradiol and progesterone in blood serum during the menstrual cycle in
      woman with acute hepatitis b].
AB  - The study was aimed at the determination of blood serum levels of the ovarian
      hormones (estradiol and progesterone) in women during the first menstrual cycle
      occurring in the course of hospitalization because of the acute viral hepatitis
      of type B, and in the same women during the first menstrual cycle occurring in
      the course of early convalescence after leaving the hospital. The observed group
      consisted of 20 women of age between 18 and 35 years treated because of acute
      hepatitis without coexisting diseases including gynecological ailments. All the
      women had a regular 28-day menstrual cycle. Twenty healthy women served as a
      control group. The blood serum concentrations of estradiol and progesterone were
      determined in all the subjects on 6-th, 12-th, 14-th, 18-th and 22-nd day of the
      menstrual cycle by RIA method using the ready made reagent kits. A significant
      decrease in the mean value of estradiol was found in the group of sick women as
      compared to the control group and to the same group of women in the course of
      early convalescence. On the other hand the value obtained during the first
      menstrual cycle after discharge from the hospital did not differ from that
      observed in healthy women. Mean value of blood serum progesterone concentration
      was higher in sick women than those in the control group and in the same women
      during convalescence all the time except on the 22-nd day of the cycle. These
      values did not differ significantly when comparing the group of sick women during
      convalescence and the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364493
TI  - [State of lipid metabolism in children and adolescents with insulin-dependent
      diabetes. I. Evaluation of lipoprotein (A) behavior in children and adolescents
      with insulin-dependent diabetes].
AB  - The level of lipoprotein Lp(a), one of the risk factors of atherosclerosis, was
      determined in 91 children and adolescents of age ranging from 3.3 to 22 years
      suffering from insulin-dependent diabetes. The changes in Lp(a) were analyzed in
      relation to the group of patients, the duration of diabetes, possible genetic
      factors, other factors predisposing to early onset of atherosclerosis, and
      occurrence of obesity in the analyzed group. The relation between the level of
      Lp(a) and other parameters of lipid metabolism (total cholesterol, triglycerides,
      phospholipids, HDL-cholesterol and apolipoprotein B) as well as a degree of
      metabolic normalization of diabetes (as assessed by the determination of
      glycosylated hemoglobin and fructosamine) was studied in addition. No relation
      between Lp(a) and the factors mentioned above, with exception of glycosylated
      hemoglobin and fructosamine concentrations, could be demonstrated. The elevated
      level of Lp(a) in children and adolescents during the period of poor metabolic
      control of diabetes may constitute an additional risk factor for early onset of
      atherogenic changes.

PMID- 1364494
TI  - [Level of calcitonin in blood serum of children with insulin dependent diabetes].
AB  - Calcitonin concentration (CT) was measured in 52 children with insulin-dependent
      diabetes (IDDM). All the patients studied were divided into three groups. The
      first group consisted of children with freshly diagnosed diabetes remaining in
      the condition of ketonemic acidosis. The second group was composed of children
      with the well controlled diabetes during the first two years od duration of the
      disease. The third group included the patients with poorly controlled diabetes of
      the duration longer than ten years having the accompanying vascular
      complications. The control values were determined in children without metabolic
      disturbances of either diabetic or other origin. CT concentration was
      significantly elevated both in the patients of the first group and those of the
      third group. In the second group the concentration of this hormone was close to
      normal. It is known that calcitonin participates in the homeostasis of calcium
      and is an important regulator of insulin secretion. The results obtained suggest
      that calcitonin may play a role both in the pathogenesis of diabetes and in
      developing of diabetic osteopenia.

PMID- 1364495
TI  - [Behavior of granulocytic receptors for Fc IgG fragment and C3 component of
      complement in patients with diabetes].
AB  - The count of peripheral neutrophils having the superficial receptors for Fc IgG
      fragment (FcR) and C3 component of the complement (CR) was determined in diabetic
      patients by using the rosette tests EA and EAC according to the modified Buescher
      method. A significantly lower percentage of neutrophils with FcR and CR receptors
      was found in patients with both insulin-dependent and noninsulin-dependent
      diabetes. The lowest values were found in noncompensated diabetes; in compensated
      diabetes they were higher but still significantly lower than in the controls. The
      difference was significant in both tests used. The results obtained suggest that
      the observed fall in the percentage of neutrophils with FcR and CR receptors is
      caused by metabolic disturbances associated with diabetes.

PMID- 1364496
TI  - [In vitro culture of fibroblasts from pubic skin of women in diagnosis of
      androgen hypersensitivity].
AB  - Intracellular metabolism of testosterone was studied in in vitro cultured skin
      fibroblasts obtained from women with idiopathic hirsutism. A significantly higher
      rate of conversion of testosterone into 5-alpha-dihydrotestosterone was found in
      these women (4.78 +/- 2.08 fmol/microgram DNA/hour) as compared to that obtained
      for skin cultures of women without symptoms of androgenization (0.98 +/- 0.37
      fmol/microgram DNA/hour). These results demonstrate that fibroblast culture may
      be useful in diagnosing the causes of hyperandrogenization in women with normal
      androgen secretion.

PMID- 1364497
TI  - [Excretion of vanillic acid and homovanillic acid and tissue distribution of
      catecholamines and their metabolites in mice with various levels of
      pigmentation].
AB  - Studies concerning metabolism of catecholamines in mice differing with respect to
      the degree of pigmentation were based on determination of daily excretion of
      vanillylmandelic and homovanillic acid and tissue content of epinephrine,
      norepinephrine, dopamine and their methoxy derivatives. It was found that
      pigmented mice excrete more homovanillic acid, the metabolite of dopamine, than
      do albinotic mice. Tissue studies have shown that the brain of albinotic mice
      contains more dopamine and kidneys more epinephrine, norepinephrine and their
      methoxy derivatives than the respective organs of the pigmented mice. The
      probable reasons of differences in the rate of inactivation of catecholamines in
      albinotic and pigmented mice have been discussed.

PMID- 1364498
TI  - [Immunoenzymatic method for determining thyroglobulin levels in human blood
      serum].
AB  - An inexpensive enzyme immunoassay method was designed for the determination of
      thyroglobulin concentration in human blood serum. The range of concentrations of
      thyroglobulin which can be measured by the method is between 6 and 800 ng/ml. The
      sensitivity of the method is comparable to that of the commercial test kits. The
      values of thyroglobulin concentration obtained with the use of the described
      method are strongly correlated (r = 0.946) with those obtained by using the
      reference method (IRMA kit of Byk, Sweden). The intraassay coefficient of
      variation ranged from 5.5 to 10.2% and interassay coefficient of variation from
      9.5 to 13.2% depending on the thyroglobulin concentration. The upper limit of
      blood serum thyroglobulin concentration in healthy subjects was 70 ng/ml. The
      results of thyroglobulin determination obtained with the described method are
      falsely lowered in the presence of antithyroglobulin antibodies; simultaneous
      determination of these antibodies is thus necessary in such a case. It seems that
      the described method may be used for monitoring the patients after surgical
      treatment of differentiated thyroid cancer aimed at early detection of
      metastases.

PMID- 1364499
TI  - Radioimmunoassay of cortisol in saliva.
AB  - A direct (without extraction) radioimmunoassay of cortisol in saliva has been
      developed. The samples of saliva were subjected to four freezing-thawing cycles
      in order to decrease viscosity which may interfere with the determination. The
      method is simple, has good specificity and reproducibility. The determination in
      saliva has also the merit of noninvasiveness, and besides, the level of cortisol
      in saliva reflects the free, biologically active fraction of the hormone in blood
      serum. The volume of saliva required does not exceed 25 microliters per tube and
      the range of concentrations is between 0.6 and 15 nanograms per milliliter (1.5
      40 nmol/l).

PMID- 1364500
TI  - [Neuroendocrine immunology--new field of interdisciplinary studies].

PMID- 1364501
TI  - The relation between the results of determination of fructosamine and
      glycosylated proteins of blood serum.
AB  - Fructosamine concentration (measured by NBT reduction method) and the
      concentration of glycosylated proteins (measured by a direct UV spectrophotometry
      upon separation from nonglycosylated proteins by means of affinity
      chromatography, have been determined simultaneously in 52 samples of blood serum
      obtained from 42 children with diabetes mellitus and 10 children without
      metabolic disorders. A highly significant positive correlation (r = 0.96, p <
      0.001) was found between the two parameters. It was concluded that fructosamine
      determination by NBT reduction test reflects the true concentration of
      glycosylated proteins of blood serum, provided that the proper correction factor
      derived from the equation of linear regression is used as shown in the following
      equation: Concentration of glycosylated proteins of blood serum in milligram =
      2.78 x (fructosamine concentration in mmol/l + 1.26).

PMID- 1364502
TI  - [Effect of tolbutamide on lipolytic processes in blood and fat tissue of rats
      maintained in normothermic and hypothermic conditions].
AB  - The effect of tolbutamide administered in vivo or added to the incubation medium
      on lipolysis in adipose tissue and in blood has been studied in rats. Tissue
      lipolysis was lowered by 118 to 156% in groups of rats receiving tolbutamide in
      vivo. The addition of tolbutamide directly to the incubation medium caused an
      increase in the lipid mobilizing activity, while the addition of insulin
      inhibited lipolysis in each case. The effect of tolbutamide administered in vivo
      may be indirect through an increase in insulin binding and/or the drug may
      influence directly the permeability of cell membrane for ions and glucose. An
      increase in the lipid mobilizing activity observed in experiments consisting in
      the addition of tolbutamide to the incubation medium may be linked to the low
      glucose level and greater demand for free fatty acids or to the low level of
      insulin in the incubation medium.

PMID- 1364503
TI  - An additional restriction fragment length polymorphism at the thyroglobulin gene.
AB  - The study was aimed at the screening of human chromosomal DNA for restriction
      fragment length polymorphism (RFLP) at the human thyroglobulin (hTg) gene locus.
      The RFLP screening was performed in a typical way. As hybridization probes were
      used 5 Pst I fragments of hTg cDNA of the total length 5.1 kb pairs cloned in pBR
      322. One not described polymorphism was found by using the probe hTg 10,
      (nucleotides from position 4830 to 5810 in the 3' flanking region of hTg).
      Restriction enzyme Msp I identified a single two allele polymorphism: A1: 3.5 kb
      and A2: 2.5 kb. Of 32 unrelated healthy individuals two were homozygous for 3.5
      kb, one was homozygous 2.5 kb and 29 were heterozygous for both 3.5 kb. and 2.5
      kb. Thus, the frequencies of the 3.5 and 2.5 kb Msp I alleles were 0.52 and 0.48
      respectively.

PMID- 1364504
TI  - [Effect of propranolol on electrophysiologic features of the heart in patients
      with hyperthyroidism].
AB  - The effect of increasing doses of intravenously administered propranolol on
      electrophysiological features of heart was studied in 17 patients with untreated
      hyperthyroidism by using the transesophageal stimulation method. A positive and
      dose-dependent effect of propranolol on the studied parameters was found with the
      normalization of the majority of disturbances taking place after the
      administration of 6 mg of propranolol. This dose was safe and well tolerated by
      the patients. The sensitivity of the auriculo-ventricular junction to propranolol
      was less pronounced during the stimulated rhythm than during the sinus rhythm.

PMID- 1364505
TI  - [Determination of antithyroid antibodies by an immunoenzymatic method; an
      adaptation for expressing results in international units].
AB  - Solid phase immunoenzymatic methods (ELISA) have been developed for the
      determination of antithyroglbulin (ATG), antimicrosomal (AMc) and antimembrane
      (ATMA) antibodies in blood serum. The results have been expressed in
      international units (IU). The level of nonspecific reaction was determined on the
      basis of 30 samples of blood serum obtained from healthy donors. The double
      standard deviation values amounted to 8 IU for antithyroglobulin antibodies, 17
      IU for antimicrosomal antibodies and 53 IU for antimembrane antibodies at the
      serum dilution of 1:100. The values of double standard deviation obtained for the
      healthy donors correspond to the borderline between the positive serum samples
      and those containing no autoantibodies. The level of autoantibodies in patients
      with autoimmune diseases of the thyroid varied considerably ranging from complete
      absence to several thousand units per milliliter in single cases.
      Antithyroglobulin antibodies were determined simultaneously by using the
      described method and the commercial kit (Walker, Cambridge) and the results
      obtained by the two methods were compared. A linear correlation with the
      correlation coefficient r = 0.93, p < 0.001 was obtained. A good but nonlinear
      correlation was demonstrated with the methods expressing the results in titre
      values.

PMID- 1364506
TI  - [Activity of angiotensin converting enzyme in women with hypothyroidism].
AB  - Serum activity of angiotensin converting enzyme (ACE) has been measured in 13
      women (mean age 43.1 years) with primary hypothyroidism by spectrofluorometric
      method of Friedland and Silverstein. The mean enzyme activity was significantly
      lower in hypothyroid patients than in healthy persons. There is no significant
      correlation between ACE activity and thyroid hormones concentration.

PMID- 1364507
TI  - [Radioimmunologic determination of pituitary autoantibodies in patients with
      Addison's disease].
AB  - The occurrence of pituitary autoantibodies was investigated in 34 patients, 25
      females and 9 males, with Addison's disease of autoimmune origin and in 10
      patients with tuberculous etiology of the disease. In both groups adrenal
      autoantibodies were also determined. Autoantibodies were determined by
      radioimmunoassay using solid phase technique in tubes coated with proteins of
      human adrenal and pituitary microsomal fractions. Pituitary autoantibodies were
      detected in 28 of 34 patients (20 females and 8 males) with autoimmune Addison's
      disease but only in 3 patients (2 females and one male) with nonimmune etiology
      of the disease. Both antipituitary and antiadrenal antibodies remain present in
      the circulation for many years as they were detected in autoimmune Addison's
      disease even after 10 or more years after the onset of the disease. There was a
      close relationship between the occurrence of pituitary antibodies and adrenal
      autoantibodies: they both appeared in the same patients and high titres of
      pituitary autoantibodies were associated with high titres of adrenal
      autoantibodies. This suggests a close similarity or identity of pituitary and
      adrenal autoantigens.

PMID- 1364508
TI  - [Effect of phenothiazine derivative on adrenal cortex response of sheep to
      repeated emotional stress].
AB  - The study was aimed at the evaluation of propiopromazine (Combelen, Bayer), a
      derivative of phenothiazine, as an agent lowering in sheep the response to
      stress. The stress of emotional origin was induced in sheep by the isolation from
      herd lasting 1 hour. The isolation experiments were repeated 6 times on the same
      group of sheep, first three isolations (1-3) in daily intervals and next three (4
      6) in weekly intervals. Propiopromazine was administered before each isolation
      experiment. The reaction of sheep to the isolation stress was weaker after
      propiopromazine administration. This was suggested by smaller increase in blood
      serum cortisol and glucose levels when compared to sheep subjected to isolation
      but not receiving the drug. Such effect was especially conspicuous during the
      course of the first isolation experiment; during the next experiments the
      difference concerning the reaction to stress between the sheep isolated from the
      herd receiving and not receiving the drug was gradually diminishing. It was shown
      in addition that propiopromazine administration to the sheep not subjected to
      stress caused an increase in cortisol level by 125 per cent and that in glucose
      level by 35 per cent. These results suggest that propiopromazine administration
      protects the organism against the effects of emotional stress only partially.
      Moreover, the effect of its administration gradually weakens with repeating of
      the stress inducing experiment, and propiopromazine itself may act as a stress
      inducing factor. It seems therefore that the use of propiopromazine and similar
      compounds as anti-stress agents may be questionable.

PMID- 1364509
TI  - [Level of erythropoietin and parathormone in blood plasma during acute rejection
      of kidney transplant].
AB  - The acute rejection of kidney transplant is accompanied by kidney ischaemia which
      in turn is a triggering factor for erythropoietin (EPO) synthesis. It was shown,
      on the other hand, that during the rejection an increase in blood serum
      parathormone (PTH) concentration takes place. The present study was aimed at
      answering the question what is the effect of acute rejection of kidney transplant
      on blood serum concentrations of EPO i PTH. Seventeen patients with kidney
      transplant participated in the study. In all the patients the investigations were
      carried out four times: 1--few days before rejection, 2--after ascertaining that
      kidney transplant is being rejected, 3--immediately after rejection, and 4--few
      days after completing the anti-rejection therapy. High doses of
      methylprednisolone were used as anti-rejection therapy. Control group consisted
      of 16 healthy persons. Acute rejection of kidney transplant was accompanied by a
      significant increase in blood serum concentrations of EPO and PTH. After
      methylprednisolone therapy, normalization of EPO and decrease in PTH
      concentration were observed in kidney transplant patients. Significant positive
      correlations were found between EPO and PTH concentrations in blood serum. It was
      concluded that acute rejection of kidney transplant is characterized by a
      significant increase in blood serum concentrations of EPO and PTH. Despite the
      existence of a significant positive correlation between blood serum
      concentrations of EPO and PTH in patients with kidney transplant, any pathogenic
      relation between the observed disturbances of secretion of the two hormones seems
      to be of little probability.

PMID- 1364510
TI  - [Calcitonin test in patients with bone changes during the course of myeloma].
AB  - Hypocalcemic response following the administration of 160 units of porcine
      calcitonin was investigated in 14 patients with bone lesions caused by myeloma
      and in 9 control subjects. Significant decrease in blood serum calcium level was
      found in 85 per cent of myeloma patients, both in those with osteolytic bone
      lesions and those with generalized osteoporosis. Moreover, in all the patients a
      significant positive correlation was found between hypocalcemic response and the
      initial blood serum calcium concentration. Calcitonin administration did not
      cause any changes in blood serum phosphate level in myeloma patients.

PMID- 1364511
TI  - Lipid disturbances in women with polycystic ovary syndrome.
AB  - Small but detectable disturbances concerning blood lipid levels manifested by
      somewhat higher concentrations of LDL-cholesterol and triglycerides as well as
      higher values of atherogenic indices expressing the ratio of cholesterol present
      in atherogenic lipoprotein fractions to that present in atheroprotective HDL
      fraction have been shown to exist in 36 women with polycystic ovary syndrome. HDL
      cholesterol concentration was lower in women with polycystic ovary syndrome than
      in healthy women. The disturbances described above were more pronounced in obese
      patients. No correlation was found between the disturbances in lipid levels and
      hormonal disturbances particularly hyperandrogenemia.

PMID- 1364512
TI  - [The effect of postural changes on functional characteristics of the left
      ventricle in nonpregnant women].
AB  - To evaluate the potential influence of positional changes on left ventricular
      performance and some hemodynamic parameters the systolic time intervals were
      measured in 90 healthy women aged 19 to 40 years. It was observed the
      prolongation of total electromechanical systole and left ventricular ejection
      time, while the preejection period was shortened in left lateral position. These
      changes were in accordance with significant decrease in systolic, diastolic and
      mean arterial blood pressure in the same position. Heart rate, calculated stroke
      volume, cardiac output and ejection fraction did not alter with positional
      changes.

PMID- 1364513
TI  - [Dental pulp in carious teeth].
AB  - Various etiologic causes lead to dental pulp changes ranging from inflammation to
      necrosis. The most frequent changes, however, are caused by bacterial activity
      and toxins from carious process. According to the opinion of various authors and
      on the basis of our investigations the conclusion can be made that all the forms
      of dental pulp changes can be developed as the sequela of the disease of
      supporting apparatus. Pathohistologic examination of dental pulp of cariously
      damaged teeth showed that the occurred changes are mostly the sequela of
      inflammation and regressive and progressive changes are found as well.

PMID- 1364514
TI  - [Pseudarthrosis of the tibia treated by the Ilizarov method].
AB  - 21 (50%) patients suffering on pseudoarthrosis tibia were treated by ilizarov
      method, from total of 42 discussed in the paper. The ilizarov method in
      combination with Judet method was used with 21 patients (50.0%) suffering on
      pseudoarthrosis tibia. Plastic procedures were performed with 12 (28.6%) covering
      the skin and soft tissues defects, while 10 (23.8) by myocutal lobes. The non
      infectious hypertrophic pseudoarthrosis cases were treated only by ilizarov
      method 14 (33.3%), while the atrophic ones (39.1%) by ilizarov Judet and
      spondioplastics. Prior infected contact pseudoarthrosis was performed with 9
      (64.3%), 6 (66.6%) only by the ilizarov method, while 3 (33.3%) by ilizarov,
      Judet and spongioplastics were performed with 3 cases (60.0%), while 2 (40.0%)
      lifting graft. Healing cases (92.9%), but we did not with 3 cases (7.1%). An
      average time of treatment was three weeks and joints rehabilitation lasted 7
      weeks.

PMID- 1364515
TI  - [ECG in patients with hemorrhagic fever].
AB  - We analyzed 128 electrocardiograms (ECG) of 43 patients with haemorrhagic fever
      associated with kidney syndrome (HFKS) during an epidemic in 1989, region around
      Sarajevo. The greatest number of alternations was noticed in toxic phase, and the
      smallest number in invasive phase of disease. All alternations were transient.
      Extended QT interval was dominant, and was found in 19 patients (45%). Tall and
      peaked T wave in the case of 17 patients or in 40%, during toxic and recovering
      phase, was the second by its frequency. As the third by its frequency, there was
      U wave manifestation. We found this kind of alternation in the case of 13
      patients or in 31%. Incomplete right bundle branch block was the most frequent
      find during invasive phase of HTKS and it was found in 3/7 of all patients. The
      same thing was found in 6 patients more, during toxic phase, so in total it was
      21%. First degree AV block was presented in 8 patients or 19%. Other finds,
      ischemia, P-pulmo, arrhythmia etc. had frequency less than 10%.

PMID- 1364516
TI  - [Speech development in children of mothers who used hormone preparations during
      pregnancy].
AB  - The exposition to sex hormones during pregnancy and their effects on fetus and
      newborns growth and development has been the subject of numerous researches. The
      former researches pointed out that the sex hormones used during pregnancy may
      have the negative effects on fetal growth. The aim of this study is to
      investigate the effects of the hormones used during pregnancy on the growth and
      development of children until the age of seventh year. The study includes 528
      children; 235 of them have been exposed to hormones during pregnancy and the
      others 293 who have not been exposed to hormones "in utero". The selection of the
      newborns and their mothers has been made according to the hormonal exposures
      during pregnancy and the delivery term. The results indicate that the average
      values of children's weight and length on the delivery in hormonal group have
      been lower than in the control group. The children in the hormonal group had the
      earlier development of the speech and less number of disorders. The assessment of
      various growth factors and children's development represents a special
      methodological and evaluation problem, because many factors have influence on the
      development of speech in children.

PMID- 1364517
TI  - [Significance of exposure of workers in the tanning industry and the prevalence
      of upper respiratory tract diseases].
AB  - Respiratory diseases are in prevalence under the other diseases in industry of
      leather. The exposition to the chemical irritances like bensen and toluene is
      very important, because a short exposition gives early symptoms. We found in 54%
      of examined population pathologic ORL cases in a sense of hypertrophic and
      atrophic forms rhinitis and pharyngitis. Bacterial flora is pathologic in 20% of
      examined workers and comparing positive bacteriologic form between nose and
      pharynges we found infections of mucose of nose more frequent than the throat.
      The occupational atmosphere and its microclime is very important in pathology of
      upper respiratory diseases. It is etiological factor in morphological changes of
      the respiratory mucosas. At the end, we can say that the ordinary monitoring
      which contains monitoring of working place, and biologic monitoring which means
      ORL, bacteriological, biochemical and toxicologic examinations must be regulated.

PMID- 1364518
TI  - [Diagnosis and therapy of systemic necrotizing vasculitis].
AB  - Through the presentation of the case of Leucocytoclastic vasculitis of a young
      man we enlighten the problems of diagnosis, differential diagnosis, ethiology,
      development of disease, and therapeutic approach. We presented the new knowledge
      in the patogenesis of changes in the vessel wall and possible correlation with
      thrombotic thrombocytopenic purpura.

PMID- 1364519
TI  - [Family medicine--now and in the future].
AB  - In this work we present our experience in providing family health care in certain
      areas of the city. This work was carried out by teams of medical doctors and
      nurses (polivalent). After 10 years of experience and the obvious positive
      effects, we can say that a general practitioner may enjoy the confidence of
      citizens in that he takes care of the whole population of certain microregion, or
      by the way, of protection families with the accent on promotion of health and
      prevention. The health of families is protected through emphasis on promotion a
      good health and prevention of disease.

PMID- 1364520
TI  - [The significance and role of medical information in decision-making in health
      care].
AB  - The resolving of medical problems and medical decision making can not be imagined
      without information which have to be qualitative, on time and correct. These
      information, in essence, are high grade material that come from different
      sources. Health, respectively medical information are generated within health
      system as the result of every day doctors' activities. The most frequent sources
      of medical information are: medical documentation, reports about the work of
      medical staff, reviews, registers, reports about demographic and vital
      statistics, reports about medical activities etc. In the article we describe
      classification of medical information, and their most important characteristics,
      as the relevance and value of medical information. We emphasize the economic
      aspect of medical information as well.

PMID- 1364521
TI  - [Consequences of abuse of inhalants].
AB  - The work reviews large scale of serious somatic and psychic damages resultant
      from chronical, but also the acute, intoxication with various solvents. It gives
      the brief description of the most frequent somatic damages that have been already
      sorted as the specific and special entities, such as the Fankony's syndrome,
      "hufer's" neuropathy and further to the characteristic psyhoorganic syndrome or
      bone marrow aplasia. Regardless it is only a simple erytheme or a serious liver
      and kidney damage appearing as a result of the solvents abuse, it is constantly
      emphasized that out of all chemical solvents, the toluene has the most pathogenic
      effect. However, the most important part of the study reviews the detailed
      description of the sniffers' sudden death syndrome. That has not been even
      mentioned in our literature so far, but in practice we have also met often this
      tragic end of the younge solvents takers.

PMID- 1364522
TI  - [Medical manuscripts at the Oriental Institute in Sarajevo].
AB  - The Manuscript Collection of the Oriental institute was one of the richest
      collections of Oriental manuscripts on the Balkans. Among numerous manuscript
      from different fields, the field of medicine and the disciplines related to it
      contained 101 papers, out of which 61 were from the field of medicine, 13 from
      pharmacology, 19 from hygiene and 5 papers from the field of sexology. Those
      manuscripts were written over centuries in the wide areas of the East to serve as
      life manuals for the people all over the world. None of those medical manuscripts
      from that collection was preserved after a barbaric setting fire on the Oriental
      Institute. That is why this memory of the manuscripts that do not exist any more
      should serve as memento for future generations.

PMID- 1364523
TI  - [The dynamics of the microbiocenosis in the burrows of the little suslik].
AB  - Microbiocoenoses being formed in burrows of little souslik have been
      investigated. Microbiocoenoses of sloping burrows have most simple organization.
      Comparative analysis of the fauna and functional structure, conducted during the
      spring-summer period, has not shown the existence of any directed process in the
      development of microbiocoenoses of sloping burrows. On the contrary,
      microbiocoenoses of vertical nest burrows can be regarded as biocoenotic systems
      dynamic in space and time. Here in the period of rodent's vital activity occurs a
      constant construction of underground passages and periodical change of nests. In
      this case the fauna of new nests is formed largely at the expense of migration of
      nidicols along free or obstructed with loose earth underground horizontal
      passages. Microbiocoenoses in burrows of different types are not connected
      between each other by morphoprocess and their development is of independent
      character.

PMID- 1364524
TI  - [Plant smells---important determinants in the behavior and rate of development of
      ixodid disease vectors].
AB  - Experiments with nymphs of Ixodes persulcatus and Dermacentor marginatus have
      shown that the rate and degree of engorgement, dropping off from the mouse,
      metamorphosis longevity and weight of emerging imagoes change under plant odour
      influence. The influence of acetone extract vapours of pepper, poplar buds,
      linden and aspen was tested. Under the influence of the vapour, acting as an
      attractant for the adults, engorgement weight of their nymphs and the weight of
      imagoes emerging from them increased; attractants change the nymph-imago
      metamorphosis duration as well. Repellent acting odours, as a rule, produce an
      opposite reaction. The phenomenon of the inversion of the infected D. marginatus
      reaction to the odour is proved in nymphs. Attractant for naive adult ticks
      (poplar buds) increased the time of feeding and weight of nymphs in comparison
      with the control. Just the opposite: nymphs infected with tick-borne encephalitis
      (TBE) virus produce an opposite reaction--weight decrease under influence of
      poplar buds as the repellent. Importance of the above phenomena for the ticks
      distribution and TBE epizootiology is discussed.

PMID- 1364525
TI  - [The origin of parasitism in trombiculid mites (Acariformes: Trombiculidae)].
AB  - On the basis of literary data and original investigations some phylogenetic,
      ecological and morphological aspects of the origin of parasitism in trombiculid
      mites are carefully considered for the first time. It is shown that parasitism in
      this group of trombidiform mites is a relatively young historical phenomenon and
      was formed after their ontogenesis had differentiated into active and quiescent
      stages. Therefore, in the life pattern of trombiculid mites the character of
      individual development, that defines their biotopical restriction, is much more
      important than the phase parasitism. Primitive organization of the digestive
      system and extraintestinal digestion, so characteristic of this group, are one of
      the main reasons of the origin of their parasitism. Under pasture conditions
      trombiculid mites, that initially were predators-entomophages with bite-sucking
      mouth parts, pass easily to parasitism on vertebrate animals and become primary
      lymphophages. They use the vertebrate host's organism exclusively as a source of
      food and by the extent of polyphagia are very close to free-living blood-sucking
      insects. Stylostome, that develops during feeding of trombiculid larvae and some
      other closely related groups of trombidiform mites, is a universal structure for
      achieving a large amount of food on a wide range of animals during a relatively
      short period of time and reflects wide host-parasite specificity of these
      parasitic mites. From the historical view the larvae of trombiculid mites did not
      pass from one group of hosts to the others, but owing to morphological
      preadaptation to parasitism passed in a definite historical period, not earlier
      than Paleogene, to parasitism on all classes of terrestrial vertebrates,
      especially on mammals, their primary hosts.

PMID- 1364526
TI  - [The ontogenetic variability of the morphometric traits of 2 species of ixodid
      ticks in the genus Rhipicephalus].
AB  - Variability of 10 morphometric characters at all phases was investigated on
      laboratory cultures of R. turanicus and R. bursa. It has been shown that
      variability increases from phase to phase. R. turanicus nymphs of both sexes
      differ in the length of gnathostoma and length of the 1st tarsus. In nymphs of R.
      bursa sexual dimorphism manifests itself on 8 characters, in all cases sizes of
      organs are greater in female nymphs. Besides, engorged female nymphs are reliably
      greater than male ones in length and mass of the body. Mature females and males
      of R. bursa also reliably differ in the total body length as well as in sizes of
      all examined structures. Females and males of R. turanicus do not differ in body
      length but differ in 9 other morphometric characters. Correlation analysis of
      characters was carried out individually for each phase and sex. Correlation
      coefficient between characters are most low in larvae. In R. turanicus male and
      female nymphs the coefficients are close. In R. bursa female nymphs correlation
      coefficients are noticeably lower than in male ones. The level of independence of
      characters in female nymphs defines the degree of manifestation of sexual
      dimorphism at this phase: the closer the links between characters, the lesser the
      number of characters revealing sexual differences. Coefficients of correlation of
      characters coincide in males of both species. In females of R. turanicus they are
      lower than in males that determines the strengthening of sexual dimorphism at the
      phase of imago.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364527
TI  - [Soluble metabolic antigens of Trichinella spiralis: their isolation and
      characteristics].
AB  - Cultivation of Trichinella muscular larvae, purified by centrifugation in 20 ...
      50% saccharose density gradient, in protein--free nutrient media at a dosage of
      3.5-.10(3) lar./ml in the presence of insulin has made it possible to obtain a
      soluble antigen of Trichinella. It has been shown by means of electrophoresis in
      polyacrylamide gel that the soluble (secretory-excretory) antigen has three
      protein fractions while the somatic Trichinella antigen has 18 fractions. It has
      been shown that the soluble (secretory-excretory) antigen can be used for
      immobilization of erythrocytes on the surface that enables the sensitivity and
      specificity of serological methods for diagnosis of trichinellosis to be
      increased.

PMID- 1364528
TI  - [A new species of Blastocystis anseri (Protista: Rhizopoda) from domestic geese].
AB  - A new species, Blastocystis anseri, was found in domestic goose. Sizes of
      blastocyst in culture are 7.5-46.2 x 7.5-46.2 m. Method of cultivation of
      Blastocystis anseri on biphase egg medium was worked out. Liquid phase can be
      made of Hank's solution or 199 medium with an addition of 30-40% hen or bovine
      serum. Optimum temperature for cultivation is 39 +/- 0.5 degree, ph 7.0-7.2.

PMID- 1364529
TI  - [Occupational hygiene in industrial assembly work].
AB  - Data on occupational hygienic characteristics of industrial-assembly work are
      reported, which have not been subject upto now to such studies. Complex hygienic
      evaluation of the basic physical and chemical factors of the working environment
      is performed as well as physiological and ergonomic characteristics of the
      principle professional groups, analysis of the occupational diseases and diseases
      with temporary disability and clinic and laboratory examinations on the workers.
      The following peculiarities of occupational hygienic aspect are established: 1.
      dynamic and multiform professional itinerary of the industrial-installing
      workers; 2. large variability in the characteristics of the physical and chemical
      factors of the working environment, most frequently surpassing the admissible
      norms and requirements, as well as the duration of exposure to them; 3.
      considerable working engagement (from 63 to 78% operation time), connected with
      heavy physical loading (dynamic and static), exceptionally unfavourable,
      compulsory and fixed working posture, possibilities of prolonged working day,
      high rate of involvement of the psychomotor sphere, analyzers and attention,
      great professional responsibility and nervous and emotional stress; 4.
      occupational and general morbidity of workers, adequate to the already
      established by the authors occupational noxa--acute poisoning with smoking gases,
      injury of the hearing, diseases as a result of overpressure of the locomotor
      apparatus and the nervous system.

PMID- 1364530
TI  - [An experimental evaluation of the acute and chronic oral toxicity of the
      antibiotic Bactericin for plant protection].
AB  - In relation to the future implementation of the antibiotic bactericin in
      agriculture are carried out acute, subacute and chronic oral experiments on 128
      male white rats and 88 female. In order to determine the parameters of acute oral
      toxicity, doses (200, 120, 80, 60, 50, 40 mg/kg) of the preparation dissolved in
      polyethylene glycol are applied. In the subacute--1/10 and 1/20 LD50, and in the
      chronic (four months)--1/50 and 1/100 LD50. The bactericin, meant for treatment
      of tomatoes before sowing, in rate of acute oral toxicity falls in class II of
      very toxic pesticides. The acute oral LD50 for male white rats is 73.0 (48.6
      109.5) mg/kg-1 and for female--58.0 (39.9-84.0) mg/kg-1. In conditions of
      subacute (30 oral applications for 45 days) and chronic (four months) experiments
      no cumulative properties are proved as well as hepatotoxic, nephrotoxic and
      neurotoxic effect. On the basis of the complex study could be accepted, that the
      dose 1/100 LD50 (0.7 mg/kg-1) for male rats and 0.4 mg/kg-1 for female) is not
      active at chronic oral introduction.

PMID- 1364531
TI  - [An evaluation of the genotoxicity activity of the microbial preparation
      bulmoscide].
AB  - The genotoxic activity of the microbial preparation bulmoscid "in vivo" for
      somatic cells of mammals is studied by micronucleus method in marrow of mice. The
      experiments are performed on inbred mice C57BL6 of both sexes at unrepeated oral
      introduction of the preparation in two doses: 2200 mg/kg-1 (2.64.10(10) cells kg
      1), and 1100 mg/kg-1 (1.32.10(10) cells kg-1) presenting 80% and respectively 40%
      of the unrepeated maximum tolerable dose of "Bulmoscid" for mice (2750 mg/kg-1).
      The genotoxic index, frequency of micronuclear polychromatophilic erythrocytes
      (MPE) in marrow is determined in dynamics on the 24, 48 and 72 hour after the
      introduction of the preparation. The data of the performed cytogenetic analysis
      in marrow of C57BL6 mice of both sexes point out that the preparation "Bulmoscid"
      possesses no clastogenic activity for mammals. The data received are extrapolated
      also in direction of absence of genotoxic potential for germinative cells.

PMID- 1364532
TI  - [The acute toxicity of the microbial preparation bulmoscide].
AB  - The acute toxicity of a new Bulgarian microbial preparation bulmoscid on the
      basis of Bacillus thuringiensis H-14 in the conditions of oral, dermal,
      inhalation and intraperitoneal introduction in experimental animals is
      determined. The assessment of toxicity is made by using toxicometric, integral,
      hematologic, histologic and microbiologic methods in accordance with Bulgarian
      and international criteria and standards. It is established, that the preparation
      bulmoscid introduced orally in dose 5500 mg.kg-1 (6.6.10(10) cell kg-1), applied
      dermally in dose 6000 mg/kg-1 (7.2.10(10) cells kg-1) and in concentrations 18
      mg.m-3 (2.2.10(8) cells m-3) for 14 day inhalation exposure, provokes no lethal
      exit and symptoms of intoxication and leads to no changes in the integral,
      hematologic and histologic investigations on experimental animals. The
      preparation belongs to the practically nontoxic substances. The studies of the
      acute toxicity show, that the microbial preparation bulmoscid offers no danger
      for appearing of oral, dermal and inhalation poisonings when observing the
      regulations for its production and use.

PMID- 1364533
TI  - [The hematological and biochemical changes in workers exposed to benzol].
AB  - The study embraces 122 workers from two productions, where the leading chemical
      noxious in the working environment is benzol. The workers are distributed in
      groups according to the calculated index of exposure in view of looking for
      dependence dose-effect. Routine indices of peripheral blood are examined as well
      as the activity of myeloperoxidase and alkaline phosphatase in leucocytes. An
      organ-orientated screening, most frequently used for assessing the state of the
      liver was used. In a large group of workers (mainly from those with high index of
      exposure) are established early changes in leucocytes: neutropenia, toxic
      granules, strongly inhibited alkaline phosphatase in the granulocytes and
      tendency to leukopenia. It was confirmed, that the strongly inhibited alkaline
      phosphatase, find, which is established also in other workers with benzol
      exposure, is an early sign for myelotoxic effect of benzol. The biochemical study
      of workers gives no data for deviations in the functional status of the liver.
      Single changes in the indices are found characterizing lipid metabolism in
      workers from Ist risk group of both productions.

PMID- 1364534
TI  - [The effect of elevated amounts of ascorbic acid on the status of the vitamin and
      lung disorders in guinea pigs inhaling styrene].
AB  - An inhalation intoxication with styrene is performed on guinea pigs--600 mg.m-3,
      5 hrs daily, 5 days weekly for a period of 4 weeks. The animals are put on regime
      lacking vitamin C. Ascorbic acid is introduced orally on 3 levels: 20 mg.kg-1
      body mass (control) and with increased quantities 60 mg.kg-1 and 240 mg.kg-1 body
      mass. On the third day the content of ascorbic acid in some biochemical
      parameters of the lung is determined. Histochemical examinations of the lung
      tissue are made. The styrene causes decrease in the ascorbic acid content in the
      lung, considerable increase of the studied enzymes (lactate- and glucose-6
      phosphate-dehydrogenase, alkaline and acidic phosphatase) and the concentration
      of the total protein in the lung. There are inflammatory, dystrophic and
      obturation changes. The raised intake of ascorbic acid 60 mg.kg-1 body mass
      doesn't effect the negative influence of styrene. The high dose (240 mg.kg-1 body
      mass) provokes increased activity of the examined enzymes. At inhalation with
      styrene this dose of ascorbic acid increases the styrene effect on the enzyme
      activity, especially of LDH and glucose-6-phosphate-dehydrogenase, without
      invigorating the pathomorphological disturbances in the lung.

PMID- 1364535
TI  - [Changes in the activity of mixed-function oxidases in workers in an artificial
      silk plant].
AB  - The carbon sulfide effect on the oxidase mixed function activity (OMF) is studied
      in 172 workers from plant producing artificial silk, distributed in 5 groups,
      according to index of exposure, defining the strength and duration of the toxic
      effect. The OMF activity is evaluated by giving aminopyrine and determining its
      metabolites in urine. The exposure to carbon sulfide effects the OMF activity. It
      is expressed by inhibition of OMF, manifested most frequently in quality
      controllers and transporters (31%) and heads of shift and section foremen (25%).
      In the remaining groups the OMF inhibition, estimated after the first aminopyrine
      metabolite, varies from 16% to 21%. Even more significant are the changes in the
      excretion of the second metabolite, where the deviation of the referent values
      reaches 56% for IInd group, 55% in IIIrd group and 45% in Ist group.

PMID- 1364536
TI  - [Atmospheric pollution in the city of Ruse and its effect on the health of the
      population].
AB  - The atmospheric air pollution in the town of Ruse and the related with that
      changes in the health status of the population has been studied. As a result of
      the transference from Giurgiu (Romania) hydrogen chloride pollution is observed.
      Immediate changes in the morbidity of respiratory diseases is determined on the
      days of pollution. There is also a durable tendency for deterioration of the
      health status of children and adults, as well as lag behind in the physical
      development of schoolchildren and aggravated functional lung indices.

PMID- 1364537
TI  - [Toxicokinetic exposure tests for chromium].
AB  - In cases of occupational exposure to chromium, very often in the organism enters
      increased quantitatively or six-valent form of metal, possessing high toxicity,
      cancerogenic and allergenic effect. Concentrations of the element in urine (CrY),
      erythrocytes (CrE) and nails (CrH) are chosen as suitable tests for evaluation of
      the exposure. The studies are performed on 151 exposed and controlled persons.
      The results received are assessed in view of their accuracy and application for
      biological control. CrY is appropriate test for evaluation of the near in time
      exposure. CrH detects the cases of occupational CrH--of increased exposure and
      deficit. On the basis of the proved dependences dose (CrB)--effect (CrY, CrE,
      CrH) in exposed workers are recommended BMAC (MAC for Cr = 0.02 mg/m3): CrY-2.3
      micrograms/l, CrE-3.6 micrograms/l CrH-2.2 micrograms/g.

PMID- 1364538
TI  - [A hygienic study of new fabrics and models for ordinary work clothing for
      healthy workers].
AB  - Of the basis of literature information for the experience of other countries,
      data from the Institute of Hygiene and Occupational Health on the hygiene of
      textile materials and clothes, results from inquiry and additionally performed
      investigations new work-clothes for health workers are proposed, which have good
      hygiene and exploitation properties and suitable functioning.

PMID- 1364539
TI  - [Lipid and mineral metabolism and morbidity with temporary loss of work capacity
      in miners].
AB  - Examination is performed on 87 miners from mine for copper production subject to
      intensive local vibrations with average rate of increase (K) of the norms for the
      individual octave frequencies 2.4 times for 3 h exposure of the working shift, as
      well as to intensive noise--113-115 dB/A equivalent level, general dust--23
      mg/m3, fine dust--3.5 mg/m3 and fine quartz--0.43 mg/m3. There are data for
      vibration effect--changes in the cold test, vibration sensoriness, ultra sound
      sonometry, in all miners. In a significant part of them are established
      dyslipoproteinemia--increase of triglycerides, total and LDL cholesterol, values
      beyond reference (mainly above the norm) of 10 electrolytes and microelements in
      blood serum (blood). An extremely high prevalence of the cases and the days of
      total morbidity with temporary disability (respectively 189.7 and 2935 per 100),
      with predominance in its structure of diseases of the central and peripheral
      nervous systems, hypertension disease, etc. The importance of vibrations for
      disorder in the metabolic processes in the organism and development of temporary
      diseases are underlined.

PMID- 1364540
TI  - [Morbidity with temporary loss of work capacity in the workers of the Belmeken
      Sestrimo hydroelectric cascade].
AB  - The present work presents the results from the analysis on the morbidity with
      temporary disability from cascade "Belmeken-Sestrimo" (n = 94, men 73, women 21).
      By means of personnel method are studied the cases of morbidity with temporary
      disability and defined the basic and enlarged number of indices, analysed in sex,
      age, length of service, nosological structure and dynamics for a period of 3
      years (1987-1989) for the 3 sites of hydroelectric cascade "Belmeken-Sestrimo",
      water-power station "Momina Klisura", hydroelectric station "Sestrimo" and water
      power station "Belmeken". The results point out to low and average levels of
      morbidity with temporary disability, with traditional arrangement of their
      nosological affiliations (diseases of the upper respiratory ways, cardio-vascular
      system, nervous system etc.). The relative part of "frequently and long suffering
      persons" is low, but to this group as potential source for increase of the level,
      structure and dynamics of morbidity with temporary disability is necessary to
      apply purposeful undertakings.

PMID- 1364541
TI  - [A clinical observation of vinyl chloride-induced disease].
AB  - Analysis is performed on the observed clinical picture of vinyl-chloride disease
      in 12 persons, developed at concentrations of toxic substance about MAC after
      exposure from 5 to 34 years. After enlarged clinical test on individual organs
      and systems the authors establish that the most frequent result of chronic
      poisoning with vinyl-chloride is the combination of peripheral neurovegetative
      symptoms with toxic hepatitis on the background of neurosis-similar (astheno
      vegetative) manifestations. In the cases, observed by the authors, the poisoning
      takes a light course affecting the neurovegetative structures and prevailing of
      the vegetovasal forms of polyneuropathy ending with Raynaud-similar syndrome, or
      affecting the distal parts of the peripheral nerves with early electromyographic
      find. The Raynaud-similar syndrome and the bone changes ad specificity to the
      clinical picture, but are not constant manifestation of poisoning and can be
      developed at more continuous occupational exposure. The authors propose a
      discussion on the legality of the appelation vinyl-chloride disease in the cases,
      when not all classical clinic symptoms are present.

PMID- 1364542
TI  - [The interaction between lead, cadmium and essential trace elements (an
      experimental study)].
AB  - An experimental study is performed on 120 white male Wistar rats with average
      weight 180-210 g. The animals are distributed in 4 groups. I group--control; II
      group--animals treated with aqua solution of cadmium sulphate; III group--animals
      treated with aqua solution of cadmium sulphate and lead acetate simultaneously
      and IV group--animals treated with aqua solution of lead acetate. The toxic
      substances are introduced per oral in dose 1/40 of LD50 and for a period of 90
      days. The animals are killed by decapitation on the 2, 4, 15, 30 and 90th day
      from the beginning of treatment. An increased content of cadmium in blood, urine
      and liver is registered in II and III group of animals, and of lead--in III and
      IV group animals. The zinc content in liver in group II is increased in
      comparison with the control group, while in group III and IV remains unchanged.
      The concentration of zinc in blood in animals from II and III group is increased.
      There is no deviation in group IV. The copper content in liver is decreased in
      II, III and IV group. There are no significant deviations in the content of
      copper in the blood of the examined groups of animals. The level of manganese in
      liver in II, III and IV group of animals is reduced. No changes in the content of
      manganese in blood are registered in the examined groups animals.

PMID- 1364543
TI  - [Toxicokinetic and toxicodynamic indices in persons exposed to lead and
      manganese].
AB  - Subject to examination are 161 workers (118 men and 43 women) in professional
      contact with manganese and lead of the agglomeration production of Kremikovtsi. A
      complex of toxicokinetic (content of manganese in blood, urine and hair) and
      toxicodynamic indices is applied. Increased levels of manganese are established
      in the examined biological media. No plumbemia above 2.88 mumol/l is registered.
      The excretion of 5-amino-levulinic acid in urine is increased at a low rate.
      There are no considerable deviations in the clinic and chemical indices.

PMID- 1364544
TI  - [Toxic lesions in workers in the pharmaceutical industry].
AB  - Clinical studies are performed on 15 workers from the chemical and pharmaceutic
      plant "Stanke Dimitrov". Seven of the workers are with acute poisoning from
      aniline and phenylhydrazine, and eight are exposed to a chronic combined effect
      of a large group of organic solvents. The clinic and laboratory examinations aim
      at clarifying the liver and kidney functions, the state of the blood and nervous
      systems. The tests embrace also blood test morphology and osmotic resistance of
      erythrocytes, iron, correlation of haemoglobin types, electrolytes, transaminase,
      GGTP, lipid metabolism, iron-binding capacity. Moderately increased transaminase
      activity is found in 2/3 of the examined. In four of the workers is registered
      expressed anaemic and lung syndrome. The following diagnoses are accepted:
      chronic combined effect of organic solvents--in 3 workers; chronic poisoning with
      aniline and other solvents--in 1; toxic hepatitis--in 4, with no data for
      poisoning--in 7. The leading clinical syndromes in acute and chronic combined
      effect of organic solvents are discussed.

PMID- 1364545
TI  - [The incidence of paraprofessional diseases in employees of the Research
      Institute of Ferrous Metallurgy in Kremikovtsi].
AB  - The health status of 200 workers from the Institute for Ferrous Metallurgy is
      studied in view of the harmful effect of the unfavourable factors of the working
      environment (noise, microclimate, toxic aerosols, gases and vapours). Internal
      examinations are also performed. A number of laboratory indices are determined in
      order to assess the liver and kidney functions. A complete blood test and lipid
      metabolism are examined. Lead and manganese are determined in blood by atomic
      absorption spectrophotometry. In 23.5% of the examined are established data for
      arterial hypertension; with diseases of the gastric-intestinal tract are 22%. The
      influence of the toxic aerosols and the nervous and psychic loading of the
      examined workers on the higher prevalence of the paraoccupational diseases are
      discussed.

PMID- 1364546
TI  - [A modern approach to socially significant occupational diseases].

PMID- 1364547
TI  - [The effect of atmospheric pollution in the city of Srednogorie on the health of
      the population].
AB  - The town of Srednogorie is one of the ecologically endangered districts of
      Bulgaria because of environmental pollution by the copper works. The morbidity of
      the population is studied in relation to the atmospheric air pollution. Basic
      pollutants are: sulphuric compounds (sulphur dioxide and sulphuric acid) and to a
      lower rate--lead and arsenic. The tendencies of air pollution are favourable,
      save lead pollution, the concentration of which increases during the last years.
      The structure of the morbidity of the population point out that there is an
      increase of the relative part of diseases, which could be related to the
      systematic effect of heavy metals and arsenic (malignant neoplasms, diseases of
      the nervous and cardiovascular system, diseases of the kidney). More frequently
      are observed acute and chronic cases of diseases of the respiratory tract.

PMID- 1364548
TI  - [An update of the Table of Occupational Diseases--a guarantee of an improvement
      in occupational disease expertise].

PMID- 1364549
TI  - [The hygienic assessment of the organization of the vocational study practice of
      students training for the job of power-generating unit operator].
AB  - The study is carried out with schoolchildren from the educative and industrial
      complex of energetics (two classes with total 60 students) at the age of 17-18,
      from the Technical College of Energetics "V. Pick"--Sofia. They are trained for
      the profession "operator on power aggregates". The investigation is performed
      during the educative and industrial practice of the students in the Heat Power
      Station "Tr. Kostov" and the Heat Power Station "Sofia", as well as in the
      training shop of the technical college. Studies are made on: the functional
      adaptation of the organism through the reactivity of the CNS, some analysers, the
      cardiovascular system and the sympathetic-adrenal system, haemopoiesis; the
      factors of the educative and industrial environment; working/professional
      maturity of the students; health status of the adolescents. The results of the
      examination show low effectiveness of the education and industrial training in
      the Heat power station or low daily and annual exposure, leading to monotony,
      hypodynamia especially when working in second shift. It is recommended the
      education and industrial practice in the secondary special schools and technical
      colleges to be carried out in training shops, educative and industrial workshops
      and at standardization of the environmental factors and organization of rational
      regime of work and rest.

PMID- 1364550
TI  - [The readiness of the young teacher for the job].
AB  - The study aims at studying the professional readiness of the young teachers
      concerning their psychic state. It includes subjective-individual determinants-
      attitude to the profession, professional choice and steadiness, professional
      skills and satisfaction. The investigation is part of a broad complex study. The
      method used is directed first of all to self-estimation of the teacher concerning
      the structural system of the pedagogic activity which embraces supplementary
      questionnaire, revealing the motivation side of the scales for self-estimation.
      The subject of the examination are teachers from primary schools with length of
      service one to five years--time for completing their adaptation to the
      profession. The investigation includes 40 teachers from the cities of Sofia and
      Burgas. A general conclusion could be made, that there is professional readiness
      of the young teacher to be up to the requirements. His/her self-estimation
      corresponds to the adaptive behaviour and the choice of profession has a
      considerable effect on the professional steadiness. The general low satisfaction
      is not a sign for dysadaptation, but this low level presupposes lack of stimuli
      for personal development and perfection.

PMID- 1364551
TI  - [The effect of living conditions in a student town in Sofia on mental illness
      morbidity].
AB  - The effect of the factors of the living environment on the health and more
      specifically on the psychic health of young people is multi-indicated and
      essential. The present profound investigation of the psychic morbidity of the
      students in Sofia during 1986/1987 according to data of the dispensary
      registration at the student polyclinic shows reliably higher values in students
      living in the student's town, especially in those of male sex. These higher
      values are due first of all to the diseases with leading psychic and social
      factors in the etiology. In spite of the possible contribution of
      "paranosological" factors, the effect of the unfavourable psycho-social factors
      result of the conditions of life in the student's town, according to our opinion,
      is essential.

PMID- 1364552
TI  - [The nutritional characteristics and the eating regimen of students].
AB  - A study is performed on the state of the daily nutrition of 82 students (40 men
      and 42 women). There are considerable deviations from the requirements for
      rational nutrition in both groups. The input of energy in men (2748 kcal) (11.5
      MJ) responds to the physiological norm, while in women it is insufficient (1907
      kcal) (7.97 MJ). The balance of the basic nutritive substances is disturbed. The
      relative part of the energy of proteins is an average 12.8%, of fats--43.5% and
      of carbohydrates--43.8%. The ratio calcium-phosphorus is 1:1.8 in men and 1:1.7
      in women. The deficit of vitamins from group B and especially from group C is
      significant. The index for consistency of nourishing nutrients used by the
      authors gives possibility for evaluating the qualitative side of nutrition on
      different energy levels. It is of special importance in the low energy regimen of
      nutrition. Recommendation is given for further investigations of nutrition and
      the health status of students in the specific conditions in our country at
      present.

PMID- 1364553
TI  - [The health aspects of the ecological problem in Bulgaria--the territorial
      settlement characteristics].
AB  - In the conditions of denaturated natural environment, quite complicated
      ecological conditions and constant deterioration of the health and demographic
      status, the material represents: a new methodical approach for assessing the
      interaction "environment-health", giving a picture of its multifactor
      stimulation; the basic features of the characteristics of the local health and
      demographic potential of the population of Bulgaria in territorial settlement
      aspect and underlined the negative tendencies and their changes, observed in
      dynamics; backed with arguments necessity for introduction of health and
      demographic criteria and conducting a policy for determination of the ecological
      risk and solving the problems, related to the evaluation and promotion of the
      environmental settlements conditions. Without formulation and introduction of
      criteria there will be no result in the ecological development of the environment
      of settlements, for they will make possible the evaluation and control of the
      effectiveness at taking into consideration the health interest of the population.

PMID- 1364554
TI  - [The evaluation of the nitrate content in river waters].
AB  - The present work gives the possibility to quality the waters of Maritsa, Iskur,
      Danube, Struma, Ogosta, Yantra and Tundzha rivers according to nitrate index, on
      the basis of monthly investigations for a period of 10 years, after the Unified
      national system. The rich content of the results and the sufficient period of
      time give grounds to calculate and draw the direction and rate of the tendency in
      the nitrate content changes, for this period, for the separate rivers--favourable
      for Struma, Iskur and Danube; with no changes for Ogosta and Yantra; pessimistic
      for Tundzha.

PMID- 1364555
TI  - [Changes in the thyroid and other internal organs of experimental animals exposed
      to a drinking regimen with a high nitrate content].
AB  - A 3-month experiment was carried out with 24 sexually mature white male rats,
      approximately the same age, "Wistar" breed, distributed in control and
      experimental groups, each of 12 rats. The experimental group received "ad
      libitum" drinking water with average nitrate content 104.3 +/- 2.5 mg/l, and the
      control group--drinking water with nitrate content 12.0 +/- 2.0 mg/l. Both groups
      received standard food special After the expire of the experimental time the
      animals were killed and some organs--thyroid gland, liver, kidneys, spleen and
      brain were macro- and microscopically examined. There were microscopic changes in
      the thyroid gland of the experimental group of animals, expressed in thyroid
      activity with rearrangement of the colloid and formation of vacuoles in the
      periphery of the folliculi. In the liver and kidneys parenchymatous granular
      dystrophy was observed.

PMID- 1364556
TI  - [The effect of chronic combined exposure to nickel and lead on the enzymatic
      indices in body uptake with the drinking water].
AB  - A toxicological experiment on white male rats was carried out for one year. They
      received simultaneously per os nickel in doses 0.005 mg/kg and lead in doses
      0.0025 mg/kg, equivalent respectively to the recommended by CMEA norms for nickel
      and hygienic norm for lead in drinking waters, as well as nickel and lead in
      doses 0.015 and 0.01 mg/kg, 0.015 and 0.1 mg/kg surpassing 3 and 4 times and 30
      and 40 times the above mentioned norms or only nickel in doses 0.015 mg/kg, after
      which their effect on some enzyme indices was studied. Tests were made on: free
      sulfhydryl groups in blood serum, heart and liver; catalase activity of blood;
      cholinesterase activity and creatinphosphatase in blood serum; cytochromoxidase
      activity in liver and heart. It is established that in combined per os effect of
      nickel and lead in doses respectively 0.15 and 0.1 mg/kg and 0.015 and 0.01
      mg/kg, as well as during independent effect of nickel with doses 0.015 mg/kg,
      occur disorders in the tissue breathing and oxyreduction processes. Nickel and
      lead in doses, equivalent to the hygienic norms, lead to no changes according to
      all studied indices.

PMID- 1364557
TI  - [Changes in the pulse variability of operators on a 12-hour work shift regimen].
AB  - Studies are carried out on 51 workers from the state works "D. Dimov"--Yambol on
      the changes of the pulse variability in the course of 12-hour day and night shift
      work and subjective evaluation of the psychosomatic complaints, in view of
      assessment the work load and strain. This investigation is performed because the
      workers have lodged a complaint against the introduction of 12-hour shift regime
      of work. It is done twice--during the day and during the night shift. No changes
      giving indication for considerable over pressure of the physiological systems and
      decrease of the working capacity have been established during the working
      process. The conclusion is that this type of working activity--12-hour shift
      schedule endangers neither the health status of the workers, nor the security and
      reliability of the system "man-machine-environment" therefore its introduction is
      not in contradiction to the physiologically well-grounded norms for the
      organization of the working process.

PMID- 1364558
TI  - [The assessment of the general functional status and of the psychosomatic
      complaints of workers at hydroelectric power plants].
AB  - Evaluation of the general functional status and psychosomatic complaints of 61
      workers from the hydroelectric power stations is made. The following methods are
      used: 1. Assessment of the general functional state, by means of computer
      analysis of the cardiac variability, analysing the changes in the values of the
      following indices: average value of the cardiac intervals (X), their standard
      deviation (SD), coefficient of variation (CV), amplitude of the mode (AMO), index
      of stress (IS), index of the vegetative balance (IVB), homeostatic index (HI).
      The last 3 indices serve for determination of the complex evaluation of chronic
      fatigue and work adaptation (ChFWA). 2. Evaluation of the psychosomatic
      complaints, by the use of a questionnaire for the subjective psychosomatic
      complaints. 3. Studying the systolic and diastolic blood pressure. The average
      values received in workers from HPS were compared with the average values of the
      population of the country and with the average values of a similar working
      activity of a group of operators from the thermal power station HPS. In
      conclusion it could be noted that concerning ChFWA the received values in workers
      from HPS are not more unfavourable generalized values from that measured in
      workers, occupied with similar type of work in other industrial branches of the
      country. However, they are with more unfavourable data in comparison with the
      workers from HPS. The subjective evaluation of the operators concerning their
      psychic and body health status is moderately worse, both in comparison with the
      values of the index for the country, and in comparison with those of the
      operators from HPS.

PMID- 1364559
TI  - [Changes in the auditory threshold of workers exposed to the combined action of
      noise and local vibrations].
AB  - Study is performed on the effect of noise and local vibrations during a combined
      effect and independently on the auditory threshold for 4 kHz. The audiometric
      data of 1242 workers from the textile industry, coal- and ore production are
      analysed. On the basis of precise assessment of the noise level and occupational
      exposure to noise and local vibrations are formed 4 groups: exposed to
      independent noise effect with intensity 90 and 100 db (spinners and dressmakers);
      exposed to combined effect of noise (91 and 103 db) and local vibrations,
      surpassing the maximum admissible norms respectively 2.5 and 3.5 times (miners of
      coal- and ore production). In view of the occupational exposure and
      standardization concerning age and length of service the audiograms of 248
      persons are examined. The following is established: different rate of increase of
      the auditory threshold for 4 kHz depending on the intensity of the factors noise
      and local vibrations in conditions of independent and combined effect: positive
      correlation with the length of service in the changes of the auditory
      sensoriness; dynamics in the increase of the auditory threshold for 4 KHz.

PMID- 1364560
TI  - [The health status of boilermakers exposed to impulse noise].

PMID- 1364561
TI  - [An automated system for the collective protection from harmful exposure to the
      Veneta superhigh-frequency electromagnetic field of military units and the
      civilian population].
AB  - In the up-to-date exploitation of electromagnetic field generators more and more
      clearly stands out the problem for radiation protection of people from the
      biological effect of microwave radiation. In order to solve this problem an
      automatized system is developed, with the purpose to define according to
      numerical methods the areas of standardized radiation, where the stay depends on
      the exposure. On the basis of the developed product are statistical data of the
      values of the ionized radiation parameters and the algorithm for radiation and
      hygienic guarantee the exploitation of products emitting superhigh frequency
      magnetic fields, the average power and strength of the energy flow of which are
      determined by the impulse power of radiation and measurement in the so called
      "free area". The system is a first stage for group protection from superhigh
      frequency electromagnetic field, which afterwards to be approbated by means of
      apparatus dosimetric examinations.

PMID- 1364562
TI  - [Body thermal status under low-temperature conditions in brewing production].
AB  - The purpose of the present study is to trace the thermal state of workers exposed
      to low temperatures in brewery production, establishing the heat loss and the
      stress of thermoregulation. The investigations are performed in the departments
      for fermentation, deposit, cask washing and filling of 3 brewery plants. In order
      to characterize the microclimate methods of thermometry, psychometry and
      catathermometry are used. The heat state is controlled by methods of subjective
      heat perception, skin temperature, average skin temperature, temperature
      gradients, oral, rectal and average body temperature and the thermal content. The
      results of the physiological examinations point out to significant loss, which
      affects not only the periphery but also the deep tissues. There is an expressed
      risk of supercooling of the organism. The data of the heat deficit impose a
      correction of the working clothes and limitation of the exposure.

PMID- 1364563
TI  - [Obstetrical anesthesia. Round table].

PMID- 1364564
TI  - [Pelvic inflammatory processes. Round table].

PMID- 1364565
TI  - [Endoscopic study of the uterine cavity. Diagnostic and therapeutic hysteroscopy.
      I. General aspects].
AB  - We present our experience in the first 236 hysteroscopic procedures in Pontificia
      Universidad Catolica of Chile. 219 were performed as part of infertility study
      and 17 were performed for other reasons. The surgical technique, type of
      anesthesia, distension procedures and complications are described. The
      correlation between hysterosalpingographic diagnosis and endoscopic vision is
      established. The preoperative diagnosis was confirmed in 82% of the uterine
      cavity synechiae, 72% of the cervical synechiae, 67% of polyps and/or myomas, and
      in 100% of uterine malformations. Myomas and/or polyps were found in 12% of
      normal appearing hysterosalpingograms.

PMID- 1364566
TI  - [Endoscopic study of the uterine cavity. II. Hysteroscopy in uterine adhesions].
AB  - The hysteroscopic study and treatment of 136 infertile patients with synechiae of
      the uterine cavity and/or cervix is presented. The preoperative diagnosis was
      established by hysterosalpingography. The correlation between the diagnosis by
      hysterosalpingography and hysteroscopy was 72% for synechiae of the cervix; 73%
      for mild synechiae; 83.3% for moderate synechiae and 75% for severe synechiae of
      the uterine cavity. All findings of synechiae were treated hysteroscopically. The
      history of abortion and puerperal infection were among the most commonly found
      amnestic data related to the genesis of synechiae. The pregnancy rate was 70%,
      and 87.5% delivered term pregnancies in patients who did not have other
      associated factors of infertility.

PMID- 1364567
TI  - [An intraoperative anatomicopathological study of myometrial penetration in
      endometrial cancer: its usefulness in making decisions on extending the primary
      surgical treatment].
AB  - The accuracy of frozen section biopsy was evaluated determining the deep of
      myometrial invasion in 30 samples of hysterectomies performed because of
      endometrial cancer. Results were compared with the definitive biopsy. Two
      sections were performed guided by the site of largest lesion seen when the uterus
      was sectioned in a frontal plane. The diagnosis of myometrial invasion was well
      determined in 29 cases with a 96.6% of accuracy. We conclude that frozen section
      is an exact and low cost method to determine intraoperatively, deep of myometrial
      invasion. This method helps the surgeon to decide the extent of surgery,
      specially if lymphadenectomy is necessary, during staging laparotomy.

PMID- 1364568
TI  - [Endometrial carcinoma. The experience of the Hospital San Juan de Dios].
AB  - Since april 1957 to april 1986, the Gynecologic Oncologic Unit of San Juan de
      Dios Hospital, Santiago, registered 255 cases of endometrial carcinoma. 48 cases
      where clinically etapified because of no previous pelviabdominal surgical
      exploration in: Stage I: 27 cases (56.3%); II: 6 (12.5%); III: 7 (14.6%); IV: 1
      (2.1%). The remainder 207 cases were surgically etapified: I: 155 cases (74.9%);
      II: 10 (4.83%); III: 31 (14.92%) and IV: 11 cases (5.32%). Fourteen patients of
      the first group and 2 of the second one received palliative therapy. Primary
      therapy was performed with curative intention in 237 cases (34 clinically
      etapified and 203 surgically etapified). Stage I: 181 cases (76.37%), (26
      clinical, 155 surgical); Stage II: 16 (4.92%). (6.10); Stage III: 31 (14.33%),
      (2.29) and Stage IV: 9 cases (4.4%), (0 + 9). Four different kinds of therapies
      were performed: A: only surgery in 153 cases (65%); B: surgery plus radiation in
      49 (21%); C: radiation plus surgery in 20 cases (8.44%) and D: only radiation in:
      15 cases (6.33%). Five years survival with no evidence of disease (SNFD) in 116
      cases (70.04% of the 237 patients), and 58 cases (24.47%) died by endometrial
      cancer; 11 (4.64%) by intercurrent disease and 2 (0.84%) were lost from follow
      up. Survivor's distribution was: Stage I: 140 (77.34%); II: 12 (75%); III: 14
      (45.16%). Five years survival according to therapy: A: 114 (74.51%); B: 36
      (73.5%; C: 15 (75%); D: 1 (8.66%). In Stage I distribution of survivor was: A:
      83.1%; B: 74.2%; C: 81.25%; and D: 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364569
TI  - [Percutaneous mitral valvuloplasty during pregnancy].
AB  - The mitral valve stenosis is the most frequently valvuloplasty in pregnant
      patients. When it carries a significant risk of mortality for both mother and
      fetus, it can be performed a surgical commissurotomy, with a high risk for the
      fetus. We report our experience in percutaneous mitral valvuloplasty (PMV) in 3
      patients during the third trimester of pregnancy with severe mitral stenosis. In
      this cases, we performed PMV in NYHA (New York Heart Association) CF III patients
      refractory to medical treatment. We used the transseptal double balloon technique
      protecting the abdominal wall using a lead apron. The mitral areas increased from
      1 to 2 cm2, without a significant development of mitral regurgitation. In all
      cases, the infants delivered at term without complications and with normal
      weight. The PMV arise like an ideal intervention for the treatment of mitral
      stenosis during pregnancy.

PMID- 1364570
TI  - [Insulinoma and pregnancy. A clinical case].
AB  - A case of pregnancy and insulinoma is presented. The diagnosis was confirmed by
      surgery and histopathology repeated episodes of hypoglycemia was the main
      clinical manifestation. The pregnancy ended, by cesarean section. A female was
      born of 2.890 g, and evolutioned in good conditions.

PMID- 1364571
TI  - [The imperforate hymen. A clinical case].
AB  - A clinical case of imperforate hymen is presented. The echography rule is
      emphasized.

PMID- 1364572
TI  - [Valproic acid and pregnancy: an unresolved problem. A clinical case].

PMID- 1364573
TI  - [Peripartal myocardiopathy].

PMID- 1364574
TI  - [Insulin resistance in gynecological endocrinology].

PMID- 1364575
TI  - [The origins of the Papanicolaou test].

PMID- 1364576
TI  - [A sexual endocrinology course].

PMID- 1364577
TI  - Positive control of gene expression in procaryotes.
AB  - In procaryotes three types of control network are involved with the regulation of
      gene expression: global control networks, operon/single gene specific regulation
      and temporal control systems. The mechanisms used for positive control include
      the use of new components of the transcription apparatus such as new RNA
      polymerases and sigma factors, the use of activator proteins and the use of
      transcription antitermination systems. For the second two mechanisms, secondary
      negative control systems may also operate to regulate the activity of activator
      proteins and transcription antitermination factors. Thus, only very rarely is
      regulation achieved by just a simple positive control system. Positive control
      circuits allow tight regulation of gene expression that is fail-safe, in that
      most mutant changes will lead to the system becoming non-inducible rather than
      lead to constitutive gene expression.

PMID- 1364578
TI  - Monoclonal antibodies: harnessing the potential.
AB  - Antibody molecules help fulfil the mandate of the mammalian immune system to
      discriminate between the body's own proteins and the foreign antigens of
      infectious agents. The exquisite specificity they exhibit for their target
      molecules has lent itself to exploitation both in the laboratory and clinical
      medicine. Nevertheless, the early reliance on polyclonal antisera as a source of
      antibodies, has highlighted problems of homogeneity and reproducibility between
      immunizations. The advent of monoclonal antibodies displaying a single predefined
      specificity has, therefore, revolutionised many areas of the biomedical sciences.
      Eighteen years after their first description, it is, however, pertinent to ask
      whether monoclonal antibodies have yet fulfilled their true potential.

PMID- 1364579
TI  - Pattern and control in bacterial colony development.
AB  - As we learn more about bacterial life in the laboratory and in nature, we
      increasingly appreciate that they are highly sensitive and sophisticated
      organisms. One of the principal new insights has been the appreciation that
      bacteria are interactive and form organized, differentiated multicellular
      communities. Colonies produced on laboratory media by the standard research
      bacterium, Escherichia coli, are excellent examples. The organization of these
      colonies can be visualized in the microscope, by macrophotography, and by the use
      of special dyes and genetic engineering techniques to reveal patterns of
      differential gene expression. Observation of the dynamics of colony growth, and
      the response of colonies to experimental disruptions of normal development,
      indicate that control systems work to produce the regular patterns observed. The
      effects of obstacles and of other colonies on gene expression patterns indicate
      that non-linear responses to chemical gradients in the substrate play an
      important coordinating role in colony development.

PMID- 1364580
TI  - Chromosome structures.
AB  - Chromosomes are large subcellular structures, visible in the light microscope,
      that are found in the nuclei of most eukaryotic cells. Each chromosome consists
      of a single very long DNA molecule that has been compacted approximately 10,000
      fold by interactions with proteins, such that the resulting chromosome structure
      fits within a typical eukaryotic nucleus of only 10 microns in diameter. Several
      levels of structural organisation are involved in the formation of chromosomes.
      Most chromosomal DNA is wrapped in left-handed superhelical turns around protein
      'spools', called histone octamers, to form nucleosomes. Arrays of these
      nucleosomes, or 'beads on a string', are further compacted into solenoidal
      structures, called 30 nm chromatin fibres. The chromatin fibres are, in turn,
      compacted approximately 250-fold to form topologically independent 'looped' DNA
      domains, each loop containing about 20,000-100,000 nucleotide pairs of DNA
      extending from a proteinaceous central scaffold. Some chromosomes, such as
      lampbrush and polytene chromosomes, can be seen in certain specialised cells
      during interphase. Metaphase chromosomes, which can be stained to reveal
      characteristic banding patterns, are formed in most eukaryotic cells during
      mitosis. Formation of chromosome structures and the nuclei that envelop them
      involves discrete steps of nucleosome assembly, scaffold assembly, and nuclear
      envelope assembly, and can be carried out in cell-free extracts of animal eggs.
      Centromeres, the regions that mediate attachment of a chromosome to a meiotic or
      mitotic spindle, and telomeres, the natural ends of chromosomes, are structures
      that ensure that the correct number of full length chromosomes are maintained
      during the cell cycle. Most chromosome structures (nucleosomes, chromatin fibres,
      and scaffold loop domains) form from virtually any DNA sequence, but centromeres
      and telomeres are both composed of specific DNA sequences complexed with specific
      binding proteins. Recently, complete DNA sequences of entire chromosomes have
      been determined, and our rapidly emerging knowledge of chromosome structures is
      beginning to provide insights into the molecular basis of human disease.

PMID- 1364581
TI  - Bacterial motility and chemotaxis.
AB  - Bacteria swim using the only rotary motor identified in biology. The membrane
      bound motor uses the gradient of protons set up across the cytoplasmic membrane
      to drive the rotation of a semi-rigid protein helix, the flagellum. Free-swimming
      bacteria randomly change direction every few seconds, but if a gradient is
      encountered the direction-changing frequency can be biased to move the bacterium
      in a favourable direction. Bacteria respond to changes in chemical concentration,
      oxygen levels, pH, the intensity or wavelength of light, temperature and in some
      cases even the Earth's magnetic field and integrate the signals to move towards
      or maintain the cells in optimum conditions for growth and division. They also
      adapt to the changes, leaving them free to respond to any subsequent stimuli.
      Therefore bacteria have something akin to a primitive nervous system, with a
      sensory system which can respond and adapt to changes and integrate physical and
      chemical signals. Chemotaxis and motility are involved in infection, both
      positive (rhizobia) and negative (pathogens) and an understanding of the unique
      nature of motility and chemotaxis in bacteria may make it possible to control
      infection. This review will give a brief general overview of current knowledge of
      bacterial motility and chemotaxis but for more detailed analysis readers are
      referred to some more specific recent reviews.

PMID- 1364582
TI  - Microbial life at high pressures.
AB  - Deep-sea environment have selected for the evolution of unusual bacterial
      extremophiles which are adapted to life at high pressures. This review briefly
      characterises barophilic bacteria; compares and contrasts high pressure effects
      on cellular and biochemical processes in both barosensitive and barophilic
      bacteria; and presents molecular and genetic approaches which have been used to
      examine the basis of high pressure sensitivity in terrestrial barosensitive
      bacteria, or to dissect barophilic processes in deep-sea bacteria.

PMID- 1364583
TI  - Chemical anatomy of antibiotic resistance: chloramphenicol acetyltransferase.
AB  - The evolution of mechanisms of resistance to natural antimicrobial substances
      (antibiotics) was almost certainly concurrent with the development in
      microorganisms of the ability to synthesise such agents. Of the several general
      strategies adopted by bacteria for defence against antibiotics, one of the most
      pervasive is that of enzymic inactivation. The vast majority of eubacteria that
      are resistant to chloramphenicol, an inhibitor of prokaryotic protein synthesis,
      owe their resistance phenotype to genes for chloramphenicol acetyltransferase
      (CAT), which catalyses O-acetylation of the antibiotic, using acetyl-CoA as the
      acyl donor. The structure of CAT is known, as are many of the properties of the
      enzyme which explain its remarkable specificity and catalytic efficiency. Less
      clear is the evolutionary pathway which has produced the different members of the
      CAT 'family' of enzymes. Hints come from other acetyltransferases which share
      structure and mechanistic features with CAT, while not being strictly
      'homologous' at the level of amino acid sequence. The 'super-family' of trimeric
      acetyltransferases appears to have in common a chemical mechanism based on a
      shared architecture.

PMID- 1364584
TI  - [The characteristics of the psychological care for HIV-infected patients].

PMID- 1364585
TI  - [The diagnostic significance of clinico-laboratory indices in mushroom
      poisoning].
AB  - Data are reported on the observation and treatment of 111 patients with mushroom
      poisoning. In 36% the poisoning was of severe and average severe degrees. Nine
      patients (8.9%) died. The main cause of death was hepatic failure. Attention is
      paid to the prognostic significance of low values of the prothrombin index for
      determination of the severity grade of liver involvement and outcome of the
      disease as well as incongruity in several cases between the blood bilirubin
      level, transaminases and severity of the patients' condition. It is emphasized
      that mushroom poisoning may be characterized by polyorganic insufficiency but in
      the absolute majority of cases hyperazotemia may have a productive and not a
      retention character and is not related to renal function decompensation.

PMID- 1364586
TI  - [The function of the free-radical oxidation system in computer workers using
      video display terminals].
AB  - Programmers working with video-display terminals showed essential disorders of
      the functional state of the free-radical oxidation system indicating an essential
      overstrain of this system, presence of its latent insufficiency characteristic of
      activation of the lipid peroxidation. Chronic overstrain of the free-radical
      oxidation system may lead to decompensation and formation of a free-radical
      pathologic process. Prophylactic measures for this category of workers are
      recommended.

PMID- 1364587
TI  - [The intravital diagnosis of primary pulmonary hypertension].
AB  - The authors present a case of during-life diagnosis of primary pulmonary
      hypertension in a 30-years-old woman. The disease had a two-years history. The
      peculiarities of this case were incoordinance of asphyxia, cyanosis, hypertrophy
      of the right heart with the level of pulmonary insufficiency. As to the
      pathogenetic type this is an acquired plexogenous variant of primary pulmonary
      hypertension.

PMID- 1364588
TI  - [Compression-ischemic peroneal neuropathy].
AB  - The clinical picture is described of 4 patients with the syndrome of lesion of
      the peroneal developing during fixation of some physiological postures (squatting
      position etc.). The pathogenetic mechanisms of the disease are discussed. The
      authors report a characteristic monotypical clinical symptom complex of
      compression-ischemic peroneal neuropathy.

PMID- 1364589
TI  - [The incidence of multiple sclerosis and the content of cobalt, boron, zinc,
      manganese and molybdenum in the arable soils of different climatic zones of
      Ukraine].
AB  - An analysis of material on the incidence of multiple sclerosis among the
      population of different soil-climatic zones of the Ukraine (steppe, forest
      steppe, woodlands) related to the content in arable lands of movable forms of
      cobalt, boron, manganese, zinc, molibden, allowed to conclude that inhabitants of
      steppes suffer less frequently of multiple sclerosis than inhabitants of forest
      land. The arable land of steppe showed a high level of cobalt content as well as
      boron and manganese while the forest lands revealed a deficit in the mentioned
      microelements.

PMID- 1364590
TI  - [Experience in training therapist interns based at the Lutsk Provincial
      Hospital].

PMID- 1364591
TI  - [The epidemiological characteristics of the health of the population in Ukraine].
AB  - The following results are summarized: 1. Integral approach to assessment of
      population health based on the concept of standard intensive values according to
      regional signs allows to realize differentially the cause and effect relations
      between disease and factors forming this disease. 2. Establishing leading
      aggressive factors that form disease in the regional aspect may become the
      essence of complex and regional medical programs and scientific approach during
      their formation. 3. Financing health programs should not include only per capita
      principles but should consider regional peculiarities of health. 4.
      Epidemiological aspects of population health is an important problem which
      requires further detailed investigation.

PMID- 1364592
TI  - [Experience in using computers to study the health status of the population of
      Ukraine].
AB  - The authors describe computer-processed materials on the health status of the
      population of the Ukraine in connection with the 1989 census. This may help in
      prognosticating studies of the health of the population up to 2010.

PMID- 1364593
TI  - [The counterflow system of the kidney (a review of the literature)].

PMID- 1364594
TI  - [The average life expectancy of the population: the regional social hygiene
      determinants].
AB  - Results are reported of a socio-hygienic study of a very important biometric
      parameter--reproduction of the population on a regional level. Changes are
      analyzed of the average life span (ALS) during the period of three postwar
      censuses. The ALS in women tended to increase as compared with men and was more
      pronounced in the rural localities. The main causes of mortality are analyzed.
      Reduction of ALS due to circulatory diseases which tended to increase during the
      intercensus periods. Recommendations are given for optimization of population
      reproduction and increase of ALS.

PMID- 1364595
TI  - [The structure of mortality from cardiovascular diseases].

PMID- 1364596
TI  - [The rheological properties of the blood in myocardial infarct patients (a review
      of the literature)].

PMID- 1364597
TI  - [Chronic hepatitis (a lecture)].

PMID- 1364598
TI  - [The causes of the development of chronic bronchitis (a review of the
      literature)].

PMID- 1364599
TI  - [The methodological bases and possibilities for the diagnosis of kidney diseases
      in the polyclinic (a lecture)].

PMID- 1364600
TI  - [The basic stages in the work of the Epidemiological Health Service of the
      Ukraine on radiation hygiene in the period following the accident at the
      Chernobyl Atomic Electric Power Station].

PMID- 1364601
TI  - [Neuroendocrine disorders at long term in persons exposed to ionizing radiation
      after the accident at the Chernobyl Atomic Electric Power Station].
AB  - Endocrinous and metabolism disorders were studied in the remote period in persons
      subjected to the effect of ionizing radiation after the Chernobyl atomic station
      accident. Results of the investigation revealed: disorders of the synthesis of
      sex hormones with small radiation doses; serotonin in increased concentration
      produced at the level of the hypothalamus a modulating effect on the pituitary
      adrenocortical system causing its functional tension; persisting functional
      changes in the central regulation link--the hypothalamus.

PMID- 1364602
TI  - [The results of a mass examination of the children of Ripkyns'kyi District,
      Chernigov Province, for thyroid status].
AB  - Mass screening of children revealed that the locality of Ripky, Chernigiv region
      showed to be a low-endemic goiter region. It was found that team screenings are
      effective.

PMID- 1364603
TI  - [The results of studies of the peripheral blood from children in Polesie
      District, Kiev Province and in the city of Kiev 4 years after the accident at the
      Chernobyl Atomic Electric Power Station].
AB  - The peripheral blood of 2200 children (age: from 2 to 16 years) inhabiting the
      Polessye District of Kiev Province and the city of Kiev 4 years after the
      Chernobyl atomic station accident was studied. An analysis of results revealed
      the presence of hematologic changes that may be interpreted as sequels of the
      effect of ionizing radiation on the body, while other changes may be considered
      as reactive and may in most cases accompany different somatic diseases of
      infectious-inflammatory character.

PMID- 1364604
TI  - [A cerebral syndrome appearing after the accident at the Chernobyl Atomic
      Electric Power Station].
AB  - Sixty participants of liquidation of the sequels of the Chernobyl atomic station
      accident were examined. All of them were subjected to the effect of different
      doses of ionizing radiation. A complex of symptoms is described characterizing
      the cerebrosthenic syndrome with vegetative paroxysms and intellectual-mnestic
      disorders. In accordance with this, approaches to treatment and rehabilitation of
      these patients are discussed.

PMID- 1364605
TI  - [Iridodiagnosis in the system of the follow-up of the health status of the
      population living in an area contaminated by radioactive substances].
AB  - The authors substantiate the practical employment of the iridodiagnosis screening
      test using a system of archiving and visualization of the iris at the first stage
      of prophylactic medical examination and management. The economical and medical
      efficacy of the method has been established. Use of iridodiagnosis improved the
      detectability of pathologic conditions as compared with complex medical
      examination. Many specialists were freed from mass medical screening. The
      expenses for prophylactic medical examination became ten times less.

PMID- 1364606
TI  - [The immunological changes in patients with idiopathic ventricular arrhythmias].

PMID- 1364607
TI  - [The structural-functional status of the myocardium and the electrophysiological
      indices in patients with atrial fibrillation].
AB  - A study is presented of 100 male patients with paroxysmal forms of atrial
      fibrillation (age: from 16 to 66 years). It is concluded that the determinant
      substrate of formation of atrial fibrillation is not limited to functional,
      electrophysiologic and morphologic state of the atria but encompasses the entire
      conduction system and structure of the myocardium both on the atrial and
      ventricular level. The frequency of paroxysms of atrial fibrillation and their
      severity are in direct dependence not only on the electrophysiological values but
      also on the degree of structural changes of the myocardium.

PMID- 1364608
TI  - [The use of enterosorption in patients in the acute period of a myocardial
      infarct].
AB  - The authors studied the clinical course of myocardial infarction during the acute
      period, the central and peripheral hemodynamics, immunological reactivity,
      dynamic electrocardiography by the Holter method in 107 patients with macrofocal
      and transmural myocardial infarction. It is concluded that it is rational include
      into the complex treatment of this condition the silicic enterosorbent
      "Polysorba". The authors recommend to begin polysorba treatment from the first
      day of onset of the disease especially in the presence of clinical signs of acute
      circulatory insufficiency. It is suggested to increase the bioavailability and
      bioassimilability of medicinal agents using the enterosorbent.

PMID- 1364609
TI  - [The amino acid-binding capacity of immunoglobulins in rheumatoid arthritis
      patients].
AB  - A study is presented of the binding capacity of immunoglobulins with amino acids
      in 60 patients with rheumatoid arthritis of grade I and II activity. Results of
      the investigation revealed an increase of the binding capacity of immunoglobulins
      of all three classes with a high range of amino acids that depended directly on
      the activity grade of the pathological process.

PMID- 1364610
TI  - [Laser correlation spectroscopy in the study of the homeostatic changes occurring
      in experimental animals after drug administration].

PMID- 1364611
TI  - [The plasma fibronectin content and its significance in patients with bronchial
      asthma].
AB  - Reduction of the content of fibronectin in blood plasma depending on severity and
      form of the disease was revealed in patients with infection-dependent bronchial
      asthma. Discreteness of influence of autologous leucocytes upon the concentration
      of fibronectin in plasma, caused by the factor of hormone dependence of the
      disease was discovered. It was determined that tactivin recovers capability of
      leucocytes in the patients with hormone dependent asthma directly (monocytes) or
      indirectly (Lymphocytes, neutrophils) to produce fibronectin.

PMID- 1364612
TI  - [The use of the immunomodulating action of intravascular laser irradiation of the
      blood in treating peptic ulcer patients].
AB  - Intravascular laser radiation of the blood was employed in 68 patients with ulcer
      disease in the complex treatment with antacid; cholinolytic, antioxidant agents.
      The employment of helium-neon laser as an immunomodulator resulted in an
      improvement of indices of cellular and humoral immunity, normalization of lipid
      peroxidation, increased resistance of the gastric and duodenal mucosa, reduction
      of the time of scarring of the ulcer defect against the background of rapid
      clinical remission, increase of the interrecurrence period.

PMID- 1364613
TI  - [The theoretical bases and clinical efficacy of acupuncture in peptic ulcer].

PMID- 1364614
TI  - [Hormonal correlations in stomach cancer patients].
AB  - The urinary excretion of andro- and glucocorticoidogenesis metabolites was
      studied in 60 patients with gastric cancer (stages II-III and IV). The
      androgenous activity showed a significant decrease that was manifested in a
      reduced excretion of 17-ketosteroids (17-KS) and their androgenicity index (AI).
      With advance of the disease stage androsterone/ethiocholanolon ratio reduced and
      became less than 1 in most patients. In patients with stage II-III gastric cancer
      there occurred a significant increase of the glucocorticoid function of the
      adrenals and a decrease in patients with stage IV cancer. Comparison with the
      androgenous activity revealed both an absolute and a relative androgenic
      insufficiency in patients with gastric cancer. It is suggested that reduced
      production of androgens effects favourably the catabolic manifestation of the
      effect of glucocorticoids. Drug-stimulated increase of the production of
      androgens in the body of patients with gastric cancer is desired.

PMID- 1364615
TI  - [The characteristics of the blood histamine indices and of the pathomorphological
      changes in the gastric mucosa of patients with multiple sclerosis].
AB  - The authors investigated the amount of blood histamine in 92 patients with
      multiple sclerosis depending on the length of the disease and its clinical form.
      The biopsies of the gastric mucosa were studied in 32 patients. It was
      established that the patients showed a high level of blood histamine (disease
      length--under 5 years) and a low level (disease length--over 5 years). The
      histologic changes were pronounced in the gastric mucosa which is evaluated as a
      complication of multiple sclerosis.

PMID- 1364616
TI  - [Tissue coagulation factors with pro- and anticoagulant activities in hepatocyte
      ultrastructures in chronic alcoholic intoxication].

PMID- 1364617
TI  - [Lipid peroxidation and composition of the erythrocyte membranes in patients with
      viral hepatitis B].
AB  - A study is presented of lipid peroxidation and composition of lipids in
      erythrocyte membranes in 39 patients with viral hepatitis B. It was established
      that the content of free cholesterol, lyzophosphatidylcholins, malonic
      dialdehyde, lipohydroperoxides showed an increase while the level of
      phospholipids and antioxidant activity decreased in all patients. In patients
      with viral hepatitis B cytolytic syndrome the content of phosphatidylcholins and
      sphingomyelins was reduced while in those with cholestasis syndrome the content
      of phosphatidylethanolamines was reduced.

PMID- 1364618
TI  - [The use of plasmapheresis in nephrological practice (a review of the
      literature)].

PMID- 1364619
TI  - [The significance of the content of connective tissue metabolites in the blood
      serum for the diagnosis of chronic viral hepatitis and liver cirrhosis].
AB  - With the purpose of improving early clinico-biochemical diagnosis of viral
      chronic active hepatitis and liver cirrhosis in children, the authors used
      indices of connective tissue metabolism--determination of free oxiprolin and
      neutral lipids in the blood serum. High levels of free oxiprolin and neutral
      lipids were revealed in patients with chronic active hepatitis and low--in liver
      cirrhosis. These data characterize different reactions of the connective tissue
      in the named diseases determined by different morphological maturity grades and
      secretory activity of fibroblasts.

PMID- 1364620
TI  - [A hygienic evaluation of the insecticide Sonet and the characteristics of the
      mechanism of its toxic action in an experiment].
AB  - A toxicological evaluation of a new insecticide Sonet was realized. It was
      established that by its toxicity Sonet belongs to hazardous substances of class
      III. The main manifestations of its toxic effect on the body warm-blooded animals
      is its influence on the erythropoiesis and functional state of the liver.

PMID- 1364621
TI  - [The effect of the individual biorhythm on conjunctival microcirculation in
      hypertension patients].
AB  - Deterioration of the condition in patients with arterial hypertension was found
      during the critical days of individual biorhythms and correlated with changes in
      the vascular and intravascular sector of the microcirculation. The peculiarities
      of individual biorhythms and state of microcirculation in patients with arterial
      hypertension allow to carry out timely and adequate drug correction of
      microcirculation disorders and central hemodynamics.

PMID- 1364622
TI  - [The use of local iodobromine baths in the early sanatorium rehabilitation of
      myocardial infarct patients with arterial hypertension].
AB  - The effect of local iodine-bromine baths at the early stage of health-resort
      treatment on the main values of the cardio-vascular system was studied in
      patients suffering of myocardial infarction with arterial hypertension. It was
      established that local iodine-bromine baths produce a more integrative effects on
      the cardiovascular system than drugs. They favour the arterial pressure
      reduction, increase of physical working capacity, normalization of the parameters
      of central hemodynamics.

PMID- 1364623
TI  - [The differential diagnosis of diffuse toxic goiter and neurocirculatory
      dystonia].

PMID- 1364624
TI  - [The treatment of the climacteric syndrome in women suffering from Itsenko
      Cushing disease and primary obesity].
AB  - Results are reported of an investigation of the hypothalamo-pituitary-ovarian
      adrenal system in 51 women suffering of Itsenko-Cushing disease, primary obesity
      and menopausal syndrome. It was found that with onset of the menopause there
      occurs an increase of the concentration of lutropin, follitropin, testosterone
      and a reduction of the level of estradiol as in the control group. At the same
      time the level of prolactin and cortisol was increased as compared with the
      control group. Parlodel treatment in combination with specific drugs proved
      efficient.

PMID- 1364625
TI  - [The characteristics of the ultrasonic study of the pancreas in the diagnosis of
      chronic pancreatitis].

PMID- 1364627
TI  - [The global rehabilitation of the stomachic patient: current and prospective
      concepts. Parma, Italy, 3-4 July 1992. Proceedings].

PMID- 1364626
TI  - [Enterosorption in the treatment of ulcerative colitis patients].
AB  - Enterodes and splenin were used in the treatment of patients with ulcerative
      colitis (idiopathic proctocolitis) in association with routine drug treatment
      while steroids were not employed. Results indicate increase of the therapeutic
      effect due to improvement of regeneration of the intestine and improvement of the
      immunity status.

PMID- 1364628
TI  - 4th Annual North American and 1990 International Cystic Fibrosis Conference.
      Arlington, Virginia, October 3-6, 1990. Program and abstracts.

PMID- 1364629
TI  - Biomechanical study of the bile duct system outside the liver.
AB  - Diseases of the bile duct system in the digestive system after surgery are
      common. In order to clarify the cause of these diseases, research on the diseases
      from a biomechanical perspective is increasing; however, the same cannot be said
      of biochemical research. In this paper, by using a new, well-devised testing
      apparatus, specimens extracted from the bile duct system of canine body are
      tested. The test data are analyzed using the finite deformation theory, and
      mechanical properties of the bile duct system outside the liver are investigated.
      The conclusions show that the viscoelasticity of the bile duct system is very
      small. In its normal physiological condition, the bile duct wall has an almost
      uniform distribution of circumferential and longitudinal stress. However, when
      the diseases of the bile duct system cause high pressure at the bile duct, the
      circumferential stress and longitudinal stress at the bile inside wall suddenly
      increase and are much larger than those stresses at the outside wall. The elastic
      modulus gradually becomes small from the common bile duct and the common hepatic
      duct to hepatic duct, and the value of elastic modulus for the cystic duct is
      almost equal to that of the hepatic duct.

PMID- 1364630
TI  - Rapid counting method of living cells by fluorescent enzyme substrates.
AB  - The 5(and 6)-carboxyfluorescein diacetate (C-FDA) is used for a rapid and
      continuous counting of living cells. Nonfluorescent C-FDA is converted into
      fluorescent 5(and 6)-carboxyfluorescein (C-F) by the reaction with esterase,
      which is an enzyme of living cells. The conversion makes it possible to count the
      number of living cells by detecting fluorescence. Experimental results show that
      the living cells of beer's yeast, E. coli, and Lactobacillus bulgaricus can be
      detected by fluorescence. The flow cell system was used to experiment a
      continuous detection of living cells, so that the number of living cells of
      beer's yeast can be detected continuously. The proposed method can be applied to
      the on-line counting in the food plants.

PMID- 1364631
TI  - Acoustical imaging and processing of blood vessel and the related materials using
      ultrasound Doppler effect.
AB  - In the present paper a method is proposed to measure the degree of the
      degradation of the elasticity in natural blood vessel and the related materials
      by using ultrasound Doppler effect. It was found that the deformation rate and
      its acceleration in the radial direction of the blood vessel can be detected by
      acoustical imaging and processing using this method. These results were proven to
      correspond to the degree of the degradation of the elasticity, that is, the
      degree of viscoelasticity in the blood vessel from the wave versus time pattern
      detected and its simple analysis. This method was applied to predicting the
      arteriosclerosis of blood vessels of humans by acoustical imaging and processing
      uninvadedly, as the characteristics of viscoelasticity in blood vessels.

PMID- 1364632
TI  - Mechanical test methods of biomedical membranes such as used for otolaryngology.
AB  - Biomedical membranes, such as artificial tympanic membranes, are subject to
      noncontact internal air pressure. To estimate mechanical characteristics of such
      membranes, it is necessary to carry out the noncontact pressure test and
      membranous contact test, in addition to the usual monotonic tensile test, by
      using a rectangular specimen cut from the membranes. In this paper, these
      mechanical test methods and results on such biomedical membranes were studied.
      Some of the authors have already presented the mechanical test methods of
      cellophane membrane for hemodialysis under applied water pressure. Herein, we are
      concerned with the mechanical test methods of biomedical membranes such as
      tympanic membrane, in which gaseous pressure was applied.

PMID- 1364633
TI  - The mechanical and microscopic aspects of the deformation and fracture of a poly
      (ether urethane-urea) spun arterial prosthesis.
AB  - The mechanical properties of a microporous, electrostatically spun poly (ether
      urethane-urea), used in the construction of arterial prostheses, have been
      examined, with particular reference to anisotropic, crack initiation processes
      and preconditioning. The results demonstrate considerable anisotropy in relation
      to samples derived from circumferential and longitudinal directions of the tube
      wall structure related to the spinning process. There is also a considerable
      difference in crack initiation on inner and outer surface of the arterial wall,
      again related to the processing conditions. The results provide an important
      contribution to an understanding of structure-property relationships in
      microporous arterial prosthesis.

PMID- 1364634
TI  - Visual evoked potential measurement by maximum length sequence technique.
AB  - The maximum length sequence (MLS) technique is applied to improve data collection
      of a clinically important long latency visual potential. Given a limited time for
      measuring the response and with low number of stimulus presentation, the MLS
      technique exceeded the conventional method of ensemble averaging in attaining a
      higher signal-to-noise ratio (SNR). The theoretical consideration of such
      improvement is developed along with the system implementation. Typical examples
      of the results obtained in a human subject are presented.

PMID- 1364635
TI  - 9th Meeting of the European Society for Neurochemistry. Dublin, Ireland, August
      16-21, 1992. Abstracts.

PMID- 1364636
TI  - [Results of endoscopic treatment of primary vesico-ureteral reflux with a follow
      up of 2-5 years].
AB  - 34 patients treated by endoscopic injection of Teflon for vesico-ureteric reflux
      were reviewed with a follow-up of 2 to 5 years. 45 of the 48 treated ureters
      showed no signs of reflux, i.e. 93.7% medium-term success rate. 3 cases of reflux
      recurred after two years and 2 of them were successfully reinjected. There were
      no upper urinary tract complications. Endoscopic injection of Teflon appears to
      be a reliable alternative to open surgery.

PMID- 1364637
TI  - [Kidney transplantation with cutaneous continent urinary diversion (apropos of 6
      cases)].
AB  - In a series of 525 renal transplantations performed between January 1987 and
      September 1990, 5 patients (i.e. 1%) presented with vesical, sphincteric and
      urethral lesions which prevented classical uretero-vesical or uretero-ureteric
      reimplantation and functionally satisfactory vesico-sphincteric reconstruction.
      Under these conditions, in which drainage of the urine into the bladder was
      impossible, a diversion was created using a continent intestinal reservoir
      constructed prior to the graft. Four Kock pouches and one Mainz pouch were
      created during the months preceding renal transplantation with a cadavre kidney.
      A sixth patient, transplanted in 1981, had to undergo continent urinary diversion
      in February 1988 after a non-functional bladder augmentation for problems of
      bladder drainage. We did not observe any mortality or major medical or surgical
      complications. The follow-up after transplantation in the first 5 patients is now
      3, 6, 10, 37 and 40 months. Renal function is normal in all 5 cases with serum
      creatinine below 130 mmol/l. For the sixth patient, the follow-up is 9 years
      after the transplantation and 32 months after the continent urinary diversion;
      serum creatinine is 200 mmol/l and stable since the urinary diversion. Continence
      is excellent and the comfort of all of the patients is undeniable. However, all
      patients present with bacteriuria with no symptomatic urinary tract infection.

PMID- 1364638
TI  - [Histologic identification of the afferent fibers of the pelvic plexus].
AB  - The inferior hypogastric (pelvic) plexus conveys two types of fibres: sympathetic
      fibres originating in the thoracolumbar sympathetic chain and parasympathetic
      fibers originating in the sacral anterior rami. By using a histofluorescent stain
      (glyoxalic acid) and a histochemical stain (thiocholine) in 17 fresh cadavres, we
      have demonstrated that the sympathetic fibres arise from sacral sympathetic
      ganglia. These fibres participate in the constitution of the pelvic splanchnic
      nerves. In this study, we confirm that the inferior roots of the pelvic plexus
      are not only parasympathetic, but also sympathetic.

PMID- 1364639
TI  - [Color processing of ultrasonographic images in extracorporeal lithotripsy].
AB  - A number of technical difficulties are encountered in the ultrasonographic
      detection of renal stones which unfortunately limit its performance. The margin
      of error of firing in extracorporeal shock-wave lithotripsy (ESWL) must be
      reduced to a minimum. The role of the ultrasonographic monitoring during
      lithotripsy is also essential: continuous control of the focussing of the short
      wave beamand assessment if the quality of fragmentation. The authors propose to
      improve ultrasonographic imaging in ESWL by means of intraoperative colour
      processing of the stone. Each shot must be directed to its target with an economy
      of vision avoiding excessive fatigue. The principle of the technique consists of
      digitalization of the ultrasound video images using a Macintosh Mac 2 computer.
      The Graphis Paint II program is interfaced directly with the Quick Capture card
      and recovers the images on its work surface in real time. The program is then
      able to attribute to each of these 256 shades of grey any one of the 16.6 million
      colours of the Macintosh universe with specific intensity and saturation. During
      fragmentation, using the principle of a palette, the stone changes colour from
      green to red indicating complete fragmentation. A Color Space card converts the
      digital image obtained into a video analogue source which is visualized on the
      monitor. It can be superimposed and/or juxtaposed with the source image by means
      of a multi-standard mixing table. Colour processing of ultrasonographic images in
      extracoporeal shockwave lithotripsy allows better visualization of the stones and
      better follow-up of fragmentation and allows the shockwave treatment to be
      stopped earlier. It increases the stone-free performance at 6 months. This
      configuration will eventually be able to integrate into the ultrasound apparatus
      itself.

PMID- 1364640
TI  - [Testicular sarcoidosis].
AB  - The authors report a case of testicular sarcoidosis. This lesion may mimic
      cancer, but the association of germ cell tumour and systemic sarcoidosis appears
      to be too frequent to be simply a coincidence. It is important to diagnose
      combinations of these 2 diseases in the scrotum or in the mediastinum, but their
      pathogenesis remains hypothetical.

PMID- 1364641
TI  - [Felix Guyon].

PMID- 1364642
TI  - [The role of LH_RH analogs in the treatment of cancer of the prostate. A report
      of the conference organized by ICI_Pharma Laboratories (part 1)].

PMID- 1364643
TI  - [Advances in urologic oncology].

PMID- 1364644
TI  - [My point of view on Peyronie's disease].

PMID- 1364645
TI  - [The modified rectal bladder for urinary diversion].

PMID- 1364646
TI  - [Immediate complications of percutaneous surgery of the kidney].

PMID- 1364647
TI  - [A practical on how to read: ultrasonograms of tumors of the kidney].

PMID- 1364648
TI  - [Bibliography of a year in urodynamics and neuro-urology].

PMID- 1364649
TI  - [Bladder substitution using the double-folded ileum technic (Goodwin's cup-patch
      technic)].
AB  - An internal urinary diversion after radical cystoprostatectomy has been performed
      in 70 male patients. The bladder substitute was made from an ileal segment,
      opened along its antimesenteric border and folded twice, according to Goodwin's
      "cup-patch technique". After an observation time of 6 months to 6 years, the
      results are in general good: The initial capacity of the pouch made from only 40
      cm of ileum (in order to avoid metabolic disturbances) increases to a functional
      capacity of 500 ml within the first postoperative weeks. The increase of the
      bladder substitute's capacity is parallel to the improvement of urinary
      continence. In general, the latter is achieved after 1-3 months during the day,
      and after 3-6 months during the night. However, loss of a few drops of urine may
      occur, reason why half of our patients wear a safety pad later than 6 months
      after surgery, at least during the night. There was no significant difference
      between those patients with an antireflux nipple and those patients having an
      ileal tubular afferent segment.

PMID- 1364650
TI  - [Ureteral replacement using an ileal graft of reduced diameter. A preliminary
      report].
AB  - Extensive or even complete loss of the ureter of a functioning kidney makes it
      impossible to restore the normal continuity of the urinary tract by any available
      surgical technique. An ileal loop of appropriate length, anastomosed to the
      bladder with its entire lumen, is the only tissue suitable for replacing this
      missing ureter; this results in the formation of a megaureter or a vesical
      diverticulum which, although contractile, presents dimensions and conditions of
      anastomosis which predispose to the development of vesico-ileal reflux and a risk
      of torpid infection and dangerous reabsorption of the urine. We consider that it
      would be useful to use the ileum to create a contractile, reduced calibre tube
      with properties similar to those of the ureter. This technique, which has rare
      indications, is feasible as illustrated by the 5 cases reported here,
      corresponding to 7 uretero-ileoplasties modelled according to this technique.
      Results were satisfactory with a follow up of 6-24 months.

PMID- 1364651
TI  - [Cryotherapy of neovascular glaucoma in diabetics].
AB  - The authors give an account of the long-term results of cryotherapy of
      neovascular glaucoma in 15 eyes of 12 patients with proliferative diabetic
      retinopathy. The operation was repeated in three instances (20%). Cyclocryothermy
      was used nine times, cyclocryothermy with retinal transconjunctival
      cryocoagulation also nine times. Within five days after operation the intraocular
      pressure was compensated in all patients. Within six months after cryotherapy the
      intraocular pressure rose above 21 Torr (2.799 kPa) in three eyes. After repeated
      cryosurgery the intraocular pressure in these eyes was normal. In the remaining
      12 eyes at the end of the observation period--average 14.7 months--the
      intraocular pressure was within the range of 4.8-20.6 Torr (0.639-2.746 kPa). The
      pain in the eye receded in 100% of the patients. After operation eventually in
      all patients rubeosis receded. Deterioration of eyesight after the operation is
      ascribed to the duration of the high intraocular pressure and gradual progression
      of the proliferative diabetic retinopathy.

PMID- 1364652
TI  - [Scleroplasty surgery. I. Results in children].
AB  - The authors give an account on the results of scleroplastic operations (according
      Pivovarov) in 159 children (298 eyes). They describe in detail the surgical
      procedure, the mechanism of action of the operation, the fate of the implanted
      material. The most suitable material for scleroplastic operations in children is
      the irradiated human sclera which caused the minimal incidence of complications.
      Most frequently eyes with the diagnosis myopia progressiva 57.7% were operated,
      another large group were eyes with the diagnosis of myopia gravis -35.2%. The
      mean age at the time of operation was 11.3 +/- 3.3 years. In myopia progressiva
      the correction was three years after operation the same or lower in 53.3% of the
      operated patients, the vision was equal or better in 80% of the operated
      patients. In children with myopia progressiva who were operated at the age of 10
      15 years, after three years no difference in vision was recorded as compared with
      the finding before operation; the correction changed on average only by 0.27
      dioptres. This result is very satisfactory, as indication for operation was
      progression of myopia by at least 1 dioptre per year before operation. In myopia
      gravis the correction was three years after operation equal or lower in 68.4% of
      operated eyes, the vision was equal or better in 81.6% of the operated eyes.
      Reinforcement of the sclera--scleroplasty--is at the moment the only rational
      therapeutic method of progressing and severe myopia.

PMID- 1364653
TI  - [Scleroplasty surgery. II. Results in adults].
AB  - The authors give an account of the results assembled in 181 patients (350 eyes)
      where scleroplasty in Pivovarov's modification was performed. 81.4% of the
      operations were indicated in myopia gravis, 91% in myopia progressiva and 5.1% in
      combination of myopia gravis and cataract. Of four implantation materials used
      the irradiated human sclera proved best. Scleroplastic operations had a
      favourable effect on the subsequent course of myopia gravis and myopia
      progressiva (followed up to four years). In both these diagnoses during the
      postoperative period a statistically significant improvement of visual acuity was
      observed, while the correction changed only slightly. Scleroplasties are a
      suitable surgical procedure in adults who suffer from progressing or severe
      myopia and give them real hope of preservation of visual functions.

PMID- 1364654
TI  - [Results of keratoplasty performed at the Eye Clinic of the ILF in Usti nad
      Labem].
AB  - The authors give an account of their experience and results with transplantations
      of the cornea in 79 eyes during a period of 44 months. They investigated the
      condition of the optic disk and visual acuity with optimal postoperative
      correction in patients after keratoplasty. In 61% of the eyes vision improved as
      compared with the condition prior to operation, in 61% of the eyes the disk of
      the donor remained clear throughout the observation period. The observation
      period was at least one month, the maximum being 44 months.

PMID- 1364655
TI  - [Panophthalmitis as a nosocomial infection].
AB  - The submitted paper deals with an epidemic of severe postoperative
      panophthalmitis, its development, course, causes and sequelae incl.
      epidemiological characteristics. The disease developed in four patients 40 hours
      after operation of cataract. Despite treatment all four patients developed
      septicaemia and therefore the affected eyeballs were eviscerated. From smears of
      the conjunctival sac of the affected patients and from the contents of the
      eviscerated eyeball Proteus mirabilis and Enterobacter cloaceae were cultivated.
      The authors draw attention to the epidemiological association with the eye lotion
      BSS which was used from which Proteus mirabilis and E. coli were cultivated and
      with the Ringer solution from which Enterobacter cloaceae and Klebsiella
      pneumoniae were cultivated. An epidemiological analysis of the epidemic was made
      and provisions were defined to rule out its recurrence.

PMID- 1364656
TI  - [Ophthalmic complications in general corticoid therapy].
AB  - The authors investigated in a group of 850 patients the influence of long-term
      general corticotherapy on the transparency of the lens and intraocular pressure
      in relation to the length of therapy, dosage, age and sex of the patient. The
      presence of posterior subcapsular cataract was revealed in 5.2% of the patient, a
      raised intraocular pressure in 12.8%. The authors reached the conclusion that the
      duration of corticotherapy did not influence in a substantial way the development
      of posterior subcapsular cataract nor of cortisone glaucoma. A dose of 10-15 mg
      per day may be considered marginal for the development of cataract; dosage has no
      basic effect on the development of glaucoma. The maximum incidence of
      complications was in advanced age groups. No predisposition as regards sex was
      observed. A significant role in the development of cortisone cataract and
      cortisone glaucoma is played by individual sensitivity to corticoids.

PMID- 1364657
TI  - [Accuracy of intraocular pressure measurement using a noncontact Keeler
      tonometer].
AB  - Using a contactless tonometer of Keeler Co. the authors assessed the intraocular
      pressure in enucleated eyeballs and compared the values with the intraocular
      pressure assessed in the eyeballs by means of a water manometer. In the second
      stage the scatter of assessed values in the eyeballs was compared with the
      scatter of values obtained by measurements in patients.

PMID- 1364658
TI  - [Analysis of patients with retinal detachment surgery performed at the Eye Clinic
      of the ILF of the Regional Hospital in Usti nad Labem 1987-1989].
AB  - In a group of 104 patients operated at the Ophthalmological Clinic in Usti nad
      Labem on account of retinal detachment in 1987-1989 the authors investigated the
      anatomical and functional results of the operation during an average period of 15
      months. Anatomical attachment of the retina was achieved in 82%; 52% of the
      patients improved from the functional aspect. In addition to vision on admission,
      discharge and during the last check-up the authors evaluated the extent of
      retinal detachment, the site of fissures, the number of myopes and aphakic
      subjects in the group and the period of retinal detachment before operation.
      There were 37.5% myopes and 27.9% aphakic patients and artephakia was recorded in
      4.8%. The duration of detachment of the retina before operation was 7.4 weeks (3
      days to 2 years). An association between the development of retinal detachment
      and injury was proved in six patients (5.8%).

PMID- 1364659
TI  - [New views on treatment of intraocular foreign bodies].
AB  - The authors evaluated the results of surgery in 130 patients operated at the
      Second Ophthalmological Clinic in 1983-1989 on account of intraocular foreign
      bodies. Extraction of the body was successful in 126 patients (96%), the function
      of the eye was preserved in 102 of 126 extracted foreign bodies (81%), a visual
      acuity of 0.5 to 1.0 was recorded in 78 eyes (60%). The authors investigated the
      relationship of functional results on the type, size and site of the intraocular
      foreign body, the way of extraction, interval between the injury and operation
      and previous attempted extractions. Analysis of results revealed the advantages
      of extraction of intraocular foreign bodies under visual control in the majority
      of foreign bodies. Intraocular foreign bodies are not an indication for immediate
      but for early operation. After careful treatment of the wound where the foreign
      body penetrated extraction may be delayed for several days before optimal
      conditions for surgery are created.

PMID- 1364660
TI  - [Cryotherapy in the treatment of vitreous hemorrhage of various origin].
AB  - In 54 eyes from the same number of patients transconjunctival cryotherapy was
      performed (12 points and 8-10 circular ones in the outer retinal periphery) to
      influence the absorption of vitreous haemorrhages of different aetiology. The
      most frequent cause was the proliferative stage of diabetic retinopathy (53.7%)
      and vascular changes in atherosclerosis (39%). Haemorrhage of the vitreous
      persisted on average for five months. Eight months after the intervention
      complete or partial reabsorption led to improvement of the eyesight in 74% of the
      patients, no change was recorded in 16.6% and further deterioration occurred in
      9.4%. No serious per- or postoperative complications were recorded, the method is
      unpretentious, can be used in ambulatory patients, it is repeatable and suitable
      also as preparation before vitreous surgery.

PMID- 1364661
TI  - [Retinal detachment after perforating eye injuries. IV. Anatomic and functional
      results of cryosurgical procedures].
AB  - In the course of ten years the authors operated 69 patients with detachment of
      the retina (DR) after perforating eye injuries, using cryosurgical methods with
      silicone episcleral implants. In 37 patients DR developed after simple
      perforation (group A) and in 32 patients after perforation of the eye with an
      intraocular foreign body (group B). In all patients the perforation affected the
      vitreous space. From the total number of patients anatomical apposition of the
      retina was achieved in 62.3%. A significant difference is the poorer anatomical
      result of the operation in the group with simple perforations without a foreign
      body 54.0%, as compared with the group after perforation with a foreign body,
      71.9%. The anatomical results were evaluated with regard to the period of DR,
      aphakia, the characteristic of the retinal defect, the type of LR and the extent
      of the operation. From the total number of successfully operated patients we
      recorded the same or better vision in 44.2% and in 51.2% poorer vision, as
      compared with that after the perforating injury of the eye. Deterioration was
      caused by the duration of DR, detachment of the macular region, an extensive
      operation and complications.

PMID- 1364662
TI  - [Principles of treatment of detachment using minimal retinal surgery].
AB  - Minimization of detachment surgery became feasible by: (1) omitting drainage of
      subretinal fluid by using elastic plombages limited to the area of the break and
      (2) meticulous search for the retinal break(s). On this premise the extent of the
      operation is solely determined by the size of the break(s) and no longer by the
      extent of the detachment. There were conceived: (1) the cryosurgical detachment
      operation in treating detachments with several breaks by single sponges (radial
      buckles whenever possible) by being permanent plombages and (2) the balloon
      operation in treating detachments with a single break by using a temporary
      plombage. These operations, being extraocular, can be applied in more than 9 of
      10 rhegmatogenous detachments and the retina will be reattached in more than 9 of
      10 cases. -However, in the presence of a problematic break (giant tear, posterior
      hole) an intraocular operation by using expanding gases (SF6, Perfluorocarbons)
      is indicated: (3) the expanding gas operation and (4) the balloon-gas procedure.
      By using the balloon-gas procedure (reducing the number of gas injections for
      treating a giant tear to one injection by providing a sufficiently large gas
      plombage) and (5) the modified balloon-gas operation with a retrohyaloidal
      injection of gas instead, a decrease of vitreoretinal complications, otherwise
      the main cause of failure, seems apparent.

PMID- 1364663
TI  - [Visual acuity and color sensitivity in retinal detachment].
AB  - In patients with unilateral detachment of the retina after successful operation
      (buckling 3x, cerclage 3x, combined operation 4x), the visual acuity was assessed
      on Snellen optotypes or Landolt's ring chart. Optotype charts with rings were
      made according to recommendations of the commission for vision of the American
      Academy of Sciences. Snellen's visual acuity of healthy and affected eyes was 6/9
      6/6. In all patients moreover sensitivity to contrast was examined assessed by
      means of a VISTESCH testing table. It was revealed that sensitivity for contrast
      in all operated eyes is significantly lower than in healthy eyes and that the
      threshold visual acuity and steepness of lines is significantly lower.

PMID- 1364664
TI  - [Pars plana vitrectomy in proliferative diabetic retinopathy. Long-term results
      and prognostic parameters in diabetics with surgery 1983-1989].
AB  - The authors evaluated the long-term results and prognostic parameters of pars
      plana vitrectomy (PPV) in complications of proliferative diabetic retinopathy in
      235 eyes of 187 diabetics operated between Jan. 1 1983 and June 30 1989. In 117
      eyes PPV was combined with implantation of silicon oil. During an average
      observation period of 27 months PPV improved markedly the visual acuity of 125
      eyes (53.2%), however a visual acuity of 0.1 or better acuity was recorded only
      in 53 eyes (22.6%). The number of successfully operated eyes declined with the
      length of the observation period from 67.7% after three months to 50% after 60
      months. Active vascular proliferation, iatrogenic fissures of the retina,
      implantation of silicone oil and postoperative development of rubeosis were
      statistically significant adverse factors from the prognostic aspect. With the
      development of new surgical procedures the importance of different prognostic
      factors changes partly.

PMID- 1364665
TI  - [Treatment of choroidal melanoma using photocoagulation].
AB  - The author defines the conditions for treatment of chorioid melanomas by
      photocoagulation which is restricted only to a small number of tumours. The
      author describes different therapeutic techniques, using photocoagulation. The
      success rate of treatment of chorioid melanomas by xenon photocoagulation is 50
      60%, similar results are obtained with laser coagulation (maily krypton or a
      combination of argon and krypton). Treatment with an argon laser alone is not
      suitable as blue light which forms 70% of the light energy does not penetrate
      into the chorioid. Green light of the argon laser is suited for use in the first
      stage of treatment, i. e. for obliteration of retinal and chorioid vessels. The
      authors treated six patients with melanoma of the chorioid using combined xenon
      argon therapy. During the average observation period of six years only one
      patient developed regression of the tumour, in another patient further growth
      ceased, but regression was not observed. In four patients on account of
      progression of the tumour the eye had to be enucleated.

PMID- 1364666
TI  - [Metamorphosis of vitelliform macular degeneration].
AB  - The authors describe the case of vitelliform macular degeneration of a mother and
      daughter whom they followed up using different examination methods incl.
      electrophysiological ones and fluorescent angiography. During the observation
      subjective deterioration of vision occurred in the daughter which was due to
      transformation of the typical picture of egg yolk into a further stage of
      pathological changes.

PMID- 1364667
TI  - [The importance of immunologic tests in endogenous uveitis].
AB  - The authors evaluate the results of immunological examination of the peripheral
      blood of 50 patients with endogenous uveitis hospitalized at the Ophthalmological
      Clinic in Plzen in 1987-1989. The authors reach the conclusion that with regard
      to contemporary, available methods we cannot expect a significant contribution of
      immunological examinations of the peripheral blood for the diagnosis of
      endogenous uveitis without systemic disease.

PMID- 1364668
TI  - [New views on the immunology and classification of uveitis].
AB  - The authors characterize the special immune status of the eye. They mention those
      anatomical and immunological characteristics of the eye which condition this
      special immune status. They also evaluate different types of classification of
      uveitis.

PMID- 1364669
TI  - [Evaluation of the long-term therapeutic effect of bacterial vaccines
      administered 1960-1968 to patients with recurrent anterior uveitis].
AB  - The authors evaluate after an interval of many years the effectiveness of
      treatment of relapsing anterior uveitis by streptococcal vaccines administered in
      the sixties by L. Klenka, I. Hana, M. Koleckarova. The evaluation is based on a
      survey conducted by means of questionnaires. After 21 years 91% of the
      respondents do not report relapses. The authors discuss possible reasons why this
      desensitization treatment is successful.

PMID- 1364670
TI  - [Ocular changes in Gardner syndrome].
AB  - In hereditary adenomatosis of the large bowel (familial polyposis)
      extraintestinal manifestations of the disease are common: hyperostosis, dental
      anomalies, soft tissue tumours, desmoid tumours etc. Patients with marked
      extracolic signs are described as patients with Gardner's syndrome. Recently a
      further sign is described--foci of congenital hypertrophy of the pigmented
      retinal epithelium. The authors examined 22 patients with confirmed hereditary
      adenomatosis (Gardner's syndrome). The typical finding of pigmented foci on the
      fundus was recorded in 18 subjects (82%) incl. 9 subjects (50%) where the finding
      was bilateral. The authors examined also 25 children of these patients. In those
      a positive finding was recorded in 11 (44%). Ophthalmological examination can
      contribute in a significant way to detection of an asymptomatic subject with
      hereditary adenomatosis, in particular when seeking risk patients in an affected
      family. Evaluation of ophthalmological changes can also contribute to the
      solution of some special genetic problems of this disease.

PMID- 1364671
TI  - [Porphyrias with cutaneous changes in Finland].

PMID- 1364672
TI  - [Etiology, treatment and prognosis of peripheral facial palsy in the light of
      Borrelia and viral antibody findings].

PMID- 1364673
TI  - [Reliability of hospital discharge data concerning diagnosis, treatments and
      accidents].

PMID- 1364674
TI  - [The Marfan syndrome gene is localized].

PMID- 1364675
TI  - [Beta cell autoantibodies that cause diabetes have been found--or not?].

PMID- 1364676
TI  - [Giant cell arteritis and blindness--a disease with minor symptoms can lead to
      severe complications].

PMID- 1364677
TI  - [LDL apheresis--an effective treatment of homozygous familial
      hypercholesterolemia].

PMID- 1364678
TI  - [The causes and management of constipation in the elderly].

PMID- 1364679
TI  - [Neurovirological diagnostics].

PMID- 1364680
TI  - [The use of nephrography in the differential diagnosis of epidemic nephritis].

PMID- 1364681
TI  - [Decade of neurobiology].

PMID- 1364682
TI  - [The aging nerve cell].

PMID- 1364683
TI  - [Growth factors as regulators of development of the nervous system].

PMID- 1364684
TI  - [Glycoproteins that mediate cell adhesion during nervous system development].

PMID- 1364685
TI  - [GABA-mediated synaptic inhibition].

PMID- 1364686
TI  - [Gamma-aminobutyric acid and its receptors--from molecular biology to clinical
      medicine].

PMID- 1364687
TI  - [Amino acids--the most common mediators in the brain].

PMID- 1364688
TI  - [The role of amines in the function of the central nervous system].

PMID- 1364689
TI  - [Neuropeptides as fine regulators of the nervous system].

PMID- 1364690
TI  - [The effect of alcohol on nerve cells].

PMID- 1364691
TI  - [Hypothalamus and the regulation of hormone secretion].

PMID- 1364692
TI  - [Regulation of sleep].

PMID- 1364693
TI  - [Neurobiology of memory].

PMID- 1364694
TI  - [Mortality rates--the background of perinatal statistics].

PMID- 1364695
TI  - [Subacute thyroiditis].

PMID- 1364696
TI  - [The use of polymerase chain reaction in the diagnosis of non-Hodgkin's
      lymphoma].

PMID- 1364697
TI  - [Ten years since eradication of smallpox].

PMID- 1364698
TI  - [Multiple sclerosis in the light of twin studies].

PMID- 1364699
TI  - [How to quit smoking?].

PMID- 1364700
TI  - [Diagnosis and treatment of endophthalmitis].

PMID- 1364701
TI  - [Saturated and unsaturated fats in the diet].

PMID- 1364702
TI  - [Is there a reason for changing the hormone treatment?].

PMID- 1364703
TI  - [Acute rupture of ankle ligaments--operation, immobilization or functional
      treatment?].

PMID- 1364704
TI  - [One year experience of levonorgestrel-releasing intrauterine device].

PMID- 1364705
TI  - [Retinopathy of prematurity].

PMID- 1364706
TI  - [Support of the spouse of the dementia patient].

PMID- 1364707
TI  - [Nitroglycerin-induced allergic contact dermatitis].

PMID- 1364708
TI  - [Diagnosis and treatment of vertigo].

PMID- 1364709
TI  - [Treatment of clavicle fractures].

PMID- 1364710
TI  - [Development of breast cancer patient's treatment. Council for Medicine of the
      Academy of Finland].

PMID- 1364711
TI  - [Organ donor statement in the driver's license].

PMID- 1364712
TI  - [Hormone resistance].

PMID- 1364713
TI  - [Cardiovascular autonomic function tests].

PMID- 1364714
TI  - [50 years since treating the first patient with penicillin].

PMID- 1364715
TI  - [What do antibiotics cure?].

PMID- 1364716
TI  - [Development of antibacterial drugs].

PMID- 1364717
TI  - [New cephalosporins and imipenem].

PMID- 1364718
TI  - [Erythromycin derivatives].

PMID- 1364719
TI  - [Fluoroquinolones].

PMID- 1364720
TI  - [Systemic antifungal drugs].

PMID- 1364721
TI  - [Antiviral drugs].

PMID- 1364722
TI  - [Antibiotic resistance].

PMID- 1364723
TI  - [Allergy to antibiotics].

PMID- 1364724
TI  - [Diarrhea caused by antibiotics].

PMID- 1364725
TI  - [Antimicrobial treatment of severe bacterial infections].

PMID- 1364726
TI  - [Antimicrobial drugs for children in outpatient clinics].

PMID- 1364727
TI  - [Antimicrobial drugs for adults in outpatient clinics].

PMID- 1364728
TI  - [Prophylactic antimicrobial drugs for travelers].

PMID- 1364729
TI  - [Molecular virology today].

PMID- 1364730
TI  - [The effects of glucocorticoids on connective tissue].

PMID- 1364731
TI  - [Rhabdomyolysis].

PMID- 1364732
TI  - [Sparing vein surgery].

PMID- 1364733
TI  - [The importance of age and gender in the treatment of hypertension].

PMID- 1364734
TI  - [Aluminum and dialysis].

PMID- 1364735
TI  - [Tissue response caused by artificial hip joint].

PMID- 1364736
TI  - [The evaluation of prognosis of breast cancer].

PMID- 1364737
TI  - [New studies on breast cancer to predict disease outcome and clinical use of
      these new tests].

PMID- 1364738
TI  - [Operative treatment of temporal epilepsy].

PMID- 1364739
TI  - [The diagnosis and treatment of Wegener's granulomatosis].

PMID- 1364740
TI  - [Familial gynecological cancer].

PMID- 1364741
TI  - [Topical retinoic acids and the aging of skin].

PMID- 1364742
TI  - [Follow-up and treatment of severe Rh immunization].

PMID- 1364743
TI  - [Irradiated eye].

PMID- 1364744
TI  - [Diagnosis and treatment of panic disorder].

PMID- 1364745
TI  - [Why is AIDS spreading so fast in Africa?].

PMID- 1364746
TI  - [Peroxisomal diseases--pediatric and neurologic differential diagnosis].

PMID- 1364747
TI  - [Small bowel transplantation].

PMID- 1364748
TI  - [The effect of home visits on children's mental health].

PMID- 1364749
TI  - [Ethical problems in the treatment of infertility].

PMID- 1364750
TI  - [Thymus--a radiological problem in children].

PMID- 1364751
TI  - [Antibiotic treatment of bacterial meningitis in children--results from a Finnish
      multicenter study].

PMID- 1364752
TI  - [Research on the myoD gene is shaking up opinions in the regulation of
      differentiation of tissues].

PMID- 1364753
TI  - [Reflex esophagitis in the elderly].

PMID- 1364754
TI  - [Aspergillus infections in patients suffering from malignant blood diseases].

PMID- 1364755
TI  - [Symptoms of Creutzfeldt-Jakob disease during mianserin therapy].

PMID- 1364756
TI  - [Isolated proteinuria in asymptomatic patients].

PMID- 1364757
TI  - [Is muscle recession catalepsy or cataplexy?].

PMID- 1364758
TI  - [Distant relatives of Finns].

PMID- 1364759
TI  - [Intensive care in Finland].

PMID- 1364760
TI  - [Selection and monitoring of patients requiring intensive care in the year 2000].

PMID- 1364761
TI  - [Psychological stress in the intensive care unit].

PMID- 1364762
TI  - [Selection of patients for intensive care and monitoring the quality of care].

PMID- 1364763
TI  - [Physiopathology of adult respiratory distress].

PMID- 1364764
TI  - [The treatment of respiratory distress].

PMID- 1364765
TI  - [The treatment principles of oxygenation disturbance of tissues in multi-organ
      failure].

PMID- 1364766
TI  - [Extracorporeal treatments of respiratory failure].

PMID- 1364767
TI  - [Operative treatment of heart failure].

PMID- 1364768
TI  - [Treatment of acute kidney failure].

PMID- 1364769
TI  - [Infections in the intensive care unit].

PMID- 1364770
TI  - [Fluid treatment and nutrition of patients in the intensive care unit].

PMID- 1364771
TI  - [Care of organ donors].

PMID- 1364772
TI  - [Psychosis in the intensive care unit].

PMID- 1364773
TI  - [Ultrasonography of the bile ducts after cholecystectomy].
AB  - The paper is concerned with the results of multiprojectional ultrasound
      investigation of the biliferous system in 68 patients at varying time after
      cholecystectomy. In most cases (77.9%) signs of dilated biliary ducts were
      undetectable. Dilatation of the hepaticodoch was most frequently determined by
      choledolithiasis, stricture or stenosing papillitis, rarely--by pancreatic head
      cancer. Investigation of the biliary ducts in patients after cholecystectomy
      should be started with ultrasound tomography; endoscopic retrograde
      cholangiopancreatography or i.v. cholangiography and dynamic cholescintigraphy
      were indicated after the detection of the signs of dilated ducts (the
      anteroposterior diameter of the common hepatic duct was over 6 mm).

PMID- 1364775
TI  - [Computed tomography in the differential diagnosis of biliary, duodenal and
      pancreatic diseases].
AB  - The paper is concerned with analysis of CT-investigation of 150 patients with
      diseases of the bilio-pancreatoduodenal area, whose diagnosis was verified
      histologically or by clinical observation over time, using other methods (USI,
      RCPG, etc.). The authors have arrived at a conclusion that for increasing the
      informative value of CT one should use various methods of a contrast study of the
      duodenum and biliary tract, electron reconstruction of CT images in different
      projections. They have pointed out the most significant differential-diagnostic
      CT signs, proposed a table to facilitate the identification of causes and a level
      of obturation of the bile ducts, the table playing an important role in a choice
      of adequate therapy.

PMID- 1364774
TI  - [Computed tomography in the diagnosis of mechanic jaundice complicated with
      diseases of the distal common bile duct].
AB  - Computerized tomography (CT) is a noninvasive indirect method of instrumental
      investigation for imaging the liver, bile ducts and the adjacent organs. CT
      enables one to confirm objectively the mechanical nature of jaundice, to assess a
      degree and level of involvement of the biliary tract, to assess the nature and
      spreading of disease. CT sensitivity for the diagnosis of pancreatic head cancer
      was 78.8%, specificity-91.3%, that for choledocholithiasis--84.6%, specificity-
      96.7%. CT in jaundice made it possible to establish diagnosis at various levels
      of accuracy: from differentiation of mechanical and parenchymatous jaundices to
      preliminary assessment of malignant tumor resectability facilitating a choice of
      surgical tactics.

PMID- 1364776
TI  - [Radiologic diagnosis of urinary tract disorders in genital endometriosis].
AB  - The paper is concerned with the results of combined investigation of 157 women
      suffering from genital endometriosis, operated on for this disease. The
      involvement of the lower parts of the ureters in a pathological process was
      detected in 48 patients before operation and in 6 patients at operation.
      Comparison of x-ray and operative findings with histology specimens made it
      possible to define endogenous and exogenous forms of ureteral endometriosis and
      three variants of an x-ray picture in this pathology (the absence of abnormal
      changes of the urinary tract, hydroureter is over the narrowed part of the
      ureter, hydroureteronephrosis). The authors have shown a high informative value
      of combined x-ray investigation and the effectiveness of its use in clinical
      practice.

PMID- 1364777
TI  - [Computed tomography in the diagnosis of asymptomatic renal cysts].
AB  - The authors analyzed CT-data on 1732 patients aged 21 to 83 to detect symptom
      free renal cysts which were found in 30% of the patients. The rates and
      prevalence of symptom-free renal cysts were studied. A high resolution was noted.
      A majority of cysts was detected in patients over 50. The rates and prevalence of
      renal cysts testified to their low clinical significance (in the authors'
      opinion).

PMID- 1364778
TI  - [Computed tomography in the diagnosis of malignant renal neoplasms and their
      dissemination].
AB  - CT, performed in 66 patients with suspected renal tumors, showed renal cell
      carcinoma in 36. Tumor spreading was correctly established in 80.6%. Accurate
      diagnosis was made in 64 of 66 cases. The authors regard CT as an effective
      method for the recognition of sizable processes and differential diagnosis of
      solid tumors. Among the visual methods of investigation, used to define a tumor
      stage, CT turned out to be the most effective one.

PMID- 1364779
TI  - [Magnetic resonance tomography in the diagnosis of renovascular hypertension].
AB  - MR tomography was used for investigation of 38 patients with renovascular
      hypertension (RVH) and 26 healthy persons. A possibility of the use and practical
      value of the method in the diagnosis and evaluation of renal function and renal
      arteries (RA) were under study. Some quantitative MRT indices were calculated
      both for the patients and healthy persons. They included spin-spin relaxation
      time, proton density, and signal intensity. These data can provide important
      information on renal function in RVH with relation to kidney sizes and the state
      of the renal parenchyma (evaluation of the cortical substance and medulla and the
      border between them). In some cases MRT ensures noninvasive diagnosis of PA
      stenosis.

PMID- 1364780
TI  - [Radiologic endovascular prosthesis of the renal arteries in patients with
      renovascular hypertension].
AB  - A high percentage of restenoses after roentgenovascular dilatation of the renal
      arteries laid the basis of a search for new therapeutic methods for these
      patients. Experiments on implantation of nitinol spiral endoprostheses showed
      their ability for long-term permeability of renal arteries, not causing their
      thrombosis and intimal spreading, destruction of formed elements of the blood,
      change in plasma proteins. Morphological investigations have shown rapid
      formation (during 14 days) of connective tissue neointima, covered on the side of
      the blood flow with the true vascular endothelium (ensuring a nonadhesive surface
      and laminar blood flow), around the coils of an endoprosthesis. This method after
      its experimental development started to be used in clinical practice. The authors
      reported the first experience in the clinical use of this method (12 patients
      with vasorenal hypertension). A 15-month follow-up revealed a stable
      antihypertensive effect in all patients.

PMID- 1364781
TI  - [Radiologic diagnosis of malignant lymphoma of the small intestine].
AB  - The authors observed 10 patients with malignant lymphoma revealed by x-ray; 2 of
      them were supposed to be afflicted with heavy alpha-chain disease with malignant
      transformation. An x-ray picture revealed a triad of pathognomonic symptoms and a
      regular parallelism of intestinal changes with clinico-laboratory findings. In
      all the cases the diagnosis was confirmed by morphological data.

PMID- 1364782
TI  - [Angiographic diagnosis of agenesia, aplasia and hypoplasia of kidneys in
      children].
AB  - Problems of the diagnosis of congenital renal developmental defects (CRDD) still
      continue to present a certain interest. Basing on their own experience in the
      diagnosis of CRDD in 188 of 527 children with renal pathology, the authors
      arrived at a conclusion that intravital diagnosis of renal aplasia was not only
      possible with the help of angiography, but also extremely necessary because
      agenesia and aplasia were two separate entities in their genesis, limiting the
      potentialities of reconstructive operations in aplasia. Hypoplasia in children
      was very frequent and was characterized by 5 types of the angiographic picture.
      Analyzing the state of the contralateral kidneys in CRDD, the authors considered
      some features of compensatory hypertrophy.

PMID- 1364783
TI  - [Renography of renal function depending on the results of radiotherapy of bladder
      cancer].
AB  - The paper is devoted to analysis of the potentialities of radionuclide renography
      as a method for assessment of the effectiveness of radiotherapy of bladder
      cancer. The results obtained suggested close correlation between change of renal
      function and the results of irradiation. Normal renal function was observed in 3
      patients, improvement--in 16 patients, and deterioration--in 8 patients whereas a
      complete effect of radiotherapy brought about the following figures: 5, 11 and 3,
      respectively. A conclusion was made of a high significance of renography
      parameters in objective assessment of the results of radiotherapy of bladder
      cancer in conjunction with other therapeutic modalities.

PMID- 1364784
TI  - [Ultrasonographic and radiographic diagnosis of breast nodules in young women].
AB  - Mammography as a priority method of diagnosis of breast nodules in young women is
      of low efficacy as a result of a dense background of the breast as distinct from
      echography permitting the detection of abnormal lesion against this background.
      Altogether 126 patients with clinical manifestations of breast nodules were
      investigated. Apparatus methods used for investigation of 38 of them, revealed
      but manifestations of fibrocystic mastopathy. Assessment of the efficacy of x-ray
      and ultrasound diagnostic methods was performed in 88 patients with breast
      nodules (the patients varied in age from 14 to 40). Radiodiagnostic accuracy in
      benign tumors was 54.1%, that in malignant tumors--78.1%. Ultrasound
      investigation proved to be the most informative method for diagnosis of breast
      nodules in young women, and the use of a proposed algorithm would permit
      optimization of the diagnostic process.

PMID- 1364785
TI  - [Computed tomography in the diagnosis of soft tissue neoplasms of the trunk and
      extremities].
AB  - Analysis of CT data on 213 patients with soft tissue and trunk tumors has shown
      that a majority of malignant and benign tumors have a similar picture (except
      lipoma). Features of the contours of a tumor and its inner structure do not
      permit the assessment of its nature. The only significant differential-diagnostic
      sign of malignant soft tissue tumors is destruction of an adjacent bone, noted in
      17.6%. The majority of malignant and benign soft tissue tumors (70.9%) on CT
      scans look like a single node; recurrent tumors look multinodular (78.2%).
      Verification of soft tissue tumors, revealed by CT, should be done using
      morphological methods.

PMID- 1364786
TI  - [Descending myelography with water-soluble contrast agents using methods of
      lateral puncture of the great occipital cistern].
AB  - A method of lateral puncture of the great occipital cistern for descending
      myelography with water soluble contrast substances was employed. It was used in
      150 neurosurgical inpatients aged 4 to 70 with various diseases of the spinal
      marrow and its coats. A new water soluble drug iopamidol-200 (or 300) (Bracco,
      Italy) was used for diagnosis of spinal tumors. The drug dosage was worked out
      for adults as well as for children. A study was made of possible side-effects on
      a vast clinical material (80 patients). The new contrast substance iopamidol
      possesses better tolerance by patients and better roentgenocontrast properties
      than amipack.

PMID- 1364787
TI  - [Radiologic diagnosis and radiotherapy of hemangiopericytoma (Review of the
      literature)].

PMID- 1364788
TI  - [Radiologic diagnosis of duodenal sarcoma].

PMID- 1364789
TI  - [Cholangiography of bile ducts using selective catheterization].
AB  - The paper is concerned with the use of selective catheterization of the bile
      ducts during endoscopic cholangiocholecystography. This method alongside with
      routine ones was employed for investigation of 82 patients with pathology of the
      hepatoduodenopancreatic area, that helped to avoid diagnostic errors.

PMID- 1364790
TI  - [Echotomographic evaluation of normal hip joints in newborns].

PMID- 1364791
TI  - [Crohn disease of the stomach and rectum].

PMID- 1364792
TI  - [Clinical and radiologic manifestations of pleural and pulmonary complications in
      sepsis].
AB  - Proceeding from the investigation and therapy of 106 patients with
      pleuropulmonary complications of sepsis the authors described clinical and x-ray
      features of different types of their course, complications and outcomes. In 58%
      of cases pulmonary lesions were detected at the stage of pyodestruction and
      pleural empyema; interstitial-focal and infiltrative pneumonias of considerable
      spreading with the development of a respiratory type of septic shock were
      observed less frequently. Pulmonary lesions in 24% were the only sign of
      septicopyemia, in 58% they prevailed in the clinical picture of polyorganic
      lesions; pleural complications developed in 32% of the patients. Convalescence
      was observed in 88 (83%) patients; they had residual bullous-sclerotic pulmonary
      changes. The lethality rate was 17%.

PMID- 1364793
TI  - [Radiologic manifestation of AIDS in disorders of thoracic and abdominal organs].

PMID- 1364794
TI  - [Radiologic pulmonary manifestations in patients with HIV virus infection].
AB  - Altogether 155 patients with a newly detected positive reaction to HIV (a human
      immunodeficiency virus) were investigated in the Republic of Burundi. Chest x-ray
      was done in 80 of them. Pulmonary tuberculosis was diagnosed in 2 of them,
      pneumonia (chronic, interstitial and bronchial)--in 15. Enhancement and deformity
      of lung marking were detected in 45 patients (coincidence with clinical signs of
      acute bronchitis was found but in 5 of them). A conclusion has been made of
      interstitial pneumonias being typical of HIV-infected patients and of frequent
      enhancement of lung marking in the preclinical stage of AIDS.

PMID- 1364795
TI  - [Clinical and radiologic manifestations of larval paragonimiasis in children].
AB  - Investigation of 60 children with acute types and 45 children with latent types
      of larval paragonimiasis (LP) has revealed various clinical and x-ray
      manifestations of this disease, spread in the southern Primorski Territory. Three
      syndromes of this disease were singled out: toxico-allergic, abdominal and
      pulmonary. X-ray investigation showed characteristic LP symptoms: exudate in the
      pleural cavity, thickening of the wall, diaphragmatic and interlobular pleura,
      sometimes--pneumothorax. Pathology of the bronchopulmonary system manifested
      itself in focal and infiltrative shadows, enhanced and deformed lung markings,
      and bullous inflation. Diagnosis and differential diagnosis must be based on
      analysis of clinical and x-ray data and the results of serological reactions.

PMID- 1364796
TI  - [Radiologic diagnosis of pathologic pulmonary changes in ischemic heart disease].
AB  - Combined chest x-ray investigation was performed in 187 CHD patients. Different
      pulmonary changes were noted in postinfarction and atherosclerotic
      cardiosclerosis as a result of congested effects in lesser circulation: they
      depended upon a stage of disturbed circulation (the more circulatory
      decompensation was noticeable, the more marked were changes in lesser
      circulation). Pulmonary and cardiac changes in patients with postinfarction
      cardiosclerosis were more frequent and marked.

PMID- 1364797
TI  - [Pulmonary sarcoidosis].

PMID- 1364798
TI  - [Endovascular embolization of arteriovenous lung fistulas (review of literature
      and own results)].
AB  - The authors analyze the literature data on and their own experience in
      endovascular closure of arteriovenous lung fistulas: 20 fistulas were closed in
      12 patients, in whom transcutaneous catheterization of the pulmonary artery was
      performed. Large-frame angiopulmonography made it possible to reveal 10 common
      arteriovenous lung fistulas (7 single and 3 multiple ones). Afterwards the
      diagnostic procedure was turned into a therapeutic one. Several types of spirals,
      spongogel fragments, pieces of felt and pools with wool were used as embolizing
      materials. All these measures resulted in hermetic closure of the arteries and a
      complete stop of pathological right-left shunting of the blood at the lung level
      and positive dynamics of blood gaseous indices.

PMID- 1364799
TI  - [Magnetic resonance tomography in the diagnosis of aneurysm and coarctation of
      the thoracic aorta].
AB  - MR-tomography (MRT) was performed in 25 patients with aneurysms and in 11 with
      coarctation of the thoracic aorta. For investigations a device with a resistive
      magnet (the force of a field--0.23 T) was used simultaneously with ECG. MRT
      revealed all cases of aortic dissection (10 patients) and one case with a false
      positive result. Oblique sections in the direction of the thoracic aorta were
      used to assess the state of the aortic arch branches. Comparison of MRT and x-ray
      computerized tomography has shown that the diagnostic value of both methods was
      almost equal, however MRT was a safer method and easier to use. MRT was shown to
      be a method of choice for diagnosis of aneurysms and coarctations of the thoracic
      aorta but cannot be a substitution for aortography.

PMID- 1364800
TI  - [Image processing of thymus tumors].
AB  - Altogether 40 thymic tumor patients were investigated. Radiograms and
      pneumomediastinograms were subjected to processing aposteriori (increased
      contrast and spatial filtration). Spatial filtration improved selective analysis
      of spatial frequencies of imaging. Processing of images specified diagnosis of
      thymomas by underlining the shapes of normal and abnormal mediastinal formations
      and signs of invasion of the pericardium and pleura.

PMID- 1364801
TI  - [Comprehensive radionuclide lung imaging in preventive mass screening of
      industrial workers].
AB  - The results of a combined roentgenoradionuclide investigation of the lungs were
      studied in 45 persons at risk of developing chronic nonspecific pulmonary
      diseases, diagnosed in a mass screening of 3000 workers at an industrial
      enterprise. The results of fluorographic, roentgenoscopic and roentgenographic
      investigations of the lungs, roentgenopneumopolygraphy and radionuclide
      investigation of lung perfusion (pulmoscintigraphy with 99mTc-labeled albumin
      macroaggregates) were compared. During this combined investigation the signs of
      nonspecific pulmonary diseases were diagnosed in 40% of the patients, changes of
      the pulmonary blood flow--in 71%, changes of ventilation--in all the examinees. A
      conclusion was made of the necessity of additional combined investigation of
      patients belonging to risk groups, identified during mass screenings.

PMID- 1364802
TI  - [Unresolved problems of radiosurgery].

PMID- 1364803
TI  - [History of development of fluorography in the USSR].

PMID- 1364804
TI  - [Ultrasound diagnosis of gallbladder and bile duct diseases].
AB  - The paper is concerned with analysis of the potentialities of ultrasound
      introscopy in the diagnosis of various diseases of the gall bladder and
      biliferous ducts in 174 patients aged 19 to 76. The accuracy of the detection of
      calcium containing concrements of the gall bladder was 98.8%, that of
      choledocholithiasis--75%, noncalculous cholecystitis--88.4%, choledochodilatation
      -71.4%. In the absence of pathological changes in the gall bladder and biliferous
      ducts the reliability of echography was 27.7 and 93.1%, respectively. Causes of
      diagnostic errors in ultrasound tomography of the biliary system were discussed,
      methods of their prevention were proposed. A diagnostic algorithm of the sequence
      of use of ultrasound introscopy and other diagnostic methods to be employed in
      clinical practice was devised.

PMID- 1364805
TI  - [Rare cases of single coronary artery].

PMID- 1364806
TI  - [A case of congenital (primary) dysimmunoglobulinemia].

PMID- 1364807
TI  - [Radiologic diagnosis of bezoars].

PMID- 1364808
TI  - [Ultrasonography in the diagnosis of Budd-Chiari syndrome].

PMID- 1364809
TI  - [A device for fixing a 18 x 24 cm cassette in a cassette holder UV-4].

PMID- 1364810
TI  - [Supporting device for electroradiography].

PMID- 1364811
TI  - [Cassette holder].

PMID- 1364812
TI  - Communication and job performance in noise: a review.

PMID- 1364813
TI  - Cellulitis after axillary lymph node dissection for carcinoma of the breast.
AB  - We present a series of patients who developed cellulitis following axillary lymph
      node dissection for carcinoma of the breast. Bacterial cultures were not helpful
      in making a diagnosis for the majority of the cases. The clinical scenario of
      upper extremity cellulitis after axillary dissection mimics the presentation of
      cellulitis in the lower extremity. Until diagnostic methods or treatment advances
      can eliminate the indications for axillary lymphadenectomy, many women treated
      for breast cancer will be at long-term risk for the development of cellulitis due
      to localized immune impairment. Patient and physician awareness of this syndrome
      is the best available tool to prevent secondary exacerbation of lymphedema.
      Prompt treatment with appropriate antibiotics appears universally successful.
      Antistreptococcal antibiotics should not be withheld pending results of blood or
      tissue cultures, since in only a few cases will a pathogen be isolated. Although
      there are no studies confirming the concept, it is likely that appropriate
      treatment for lymphedema may reduce the risk of infection.

PMID- 1364814
TI  - Epidemiology of invasive childhood pneumococcal infections in Israel. The Israeli
      Pediatric Bacteremia and Meningitis Group.
AB  - OBJECTIVE: To study the epidemiology of childhood pneumococcal invasive
      infections in Israel as a background for immunization programs. DESIGN: A 2-year
      (October 1988 through September 1990) prospective, nationwide surveillance of all
      invasive pediatric pneumococcal infections. SETTING: All 25 medical centers
      hospitalizing children in Israel, including all laboratories performing blood
      cultures from pediatric patients. PATIENTS: Infants and children aged 0 to 12
      years visiting the pediatric emergency department or hospitalized in pediatric
      departments were included if Streptococcus pneumoniae was isolated from blood or
      cerebrospinal fluid. RESULTS: Four hundred sixty-nine invasive infections were
      diagnosed. Pneumonia, bacteremia without apparent focus, meningitis, and
      cellulitis were found in 39%, 37%, 17%, and 3%, respectively. The annual
      incidence was 42 per 100,000 for children younger than 5 years of age (104 per
      100,000 for those < 12 months old). The two most common serotypes were 1 and 5,
      which are rare in Western Europe and North America. Eight groups comprised 82% of
      all invasive infections. Extrapolated to a population in which 100,000 live
      births occur yearly, the total annual hospitalizations for pneumococci infections
      was calculated to be 1928 days. The overall case-fatality rate was 2.2%, but it
      was 30% during the first month of life. CONCLUSIONS: Pneumococcal invasive
      infections are common in children in Israel and carry considerable morbidity.

PMID- 1364815
TI  - Akathisia, suicidality, and fluoxetine.
AB  - BACKGROUND: The propose link between fluoxetine and suicidal ideation is
      explained by fluoxetine-induced akathisia and other dysphoric extrapyramidal
      reactions. METHOD: The following literature is reviewed: (1) the subjective
      response of schizophrenics to akathisia, including evidence that akathisia gives
      rise to suicidal ideation; (2) the subjective reports of patients taking
      fluoxetine; and (3) preclinical studies describing the role of serotonin in the
      extrapyramidal system and suggesting a mechanism whereby fluoxetine can induce
      extrapyramidal side effects. RESULTS: The literature suggests that fluoxetine
      induced extrapyramidal reactions may be a mediator of de novo suicidal ideation.
      CONCLUSION: We propose a syndrome which we name Extrapyramidal-Induced Dysphoric
      Reactions, one extreme manifestation of which is the emergence of suicidal
      ideation. We further propose a heuristic "Four Neuron Model of the Extrapyramidal
      Motor System" in which increased serotonin activity, by inhibiting the
      nigrostriatal dopamine tract, is capable of inducing extrapyramidal side effects.

PMID- 1364816
TI  - Occult sacral fractures in osteopenic patients.
AB  - The presentation, diagnosis, and treatment of occult sacral fractures in
      seventeen osteopenic patients were reviewed. Sixteen of the seventeen patients
      were elderly women, and the fracture usually occurred without trauma (fourteen
      patients). In ten patients, the sacral fracture was associated with a fracture of
      the pubic ramus. The sacral fractures were difficult to diagnose because nine
      patients also had a history of a malignant lesion of the pelvis with or without
      radiation treatment. Computed tomography and bone-scanning were diagnostic in all
      patients, but magnetic resonance imaging was not specific. Use of crutches or a
      walker, a reduction in activity, and use of non-narcotic analgesics allowed for
      the resolution of symptoms in all twelve patients who did not have mitigating
      conditions and permitted these patients to walk independently.

PMID- 1364817
TI  - Sequences of the envM gene and of two mutated alleles in Escherichia coli.
AB  - The nucleotide sequence of the Escherichia coli envM gene was determined. It
      codes for a protein of 262 amino acids. The sequences of the E. coli and
      Salmonella typhimurium EnvM proteins are 98% identical. Gene envM is preceded in
      E. coli by a 43-nucleotide-long structural element, termed 'box c', which occurs
      in several E. coli operons between structural genes. This sequence element is
      totally absent in S. typhimurium. Gene envM was mapped at coordinate position
      1366.8 kb of the physical map of Kohara et al. (Cell, 1987, 50, 495-508). As in
      S. typhimurium, a Gly for Ser exchange at position 93 of the amino acid sequence
      leads to a diazaborine-resistant E. coli phenotype. A Ser for Phe exchange at
      position 241 of the EnvM protein results in a temperature-sensitive growth
      phenotype. Comparison of the EnvM amino acid sequence with sequences available in
      databases showed significant homology with the family of short-chain alcohol
      dehydrogenases.

PMID- 1364818
TI  - Peristalsis evoked by 5-HT and renzapride: evidence for putative 5-HT4 receptor
      activation.
AB  - The effect of 5-hydroxytryptamine and renzapride was studied on the peristaltic
      reflex elicited in vitro in the guinea-pig ileum. Both agents evoked the reflex
      at subthreshold intraluminal pressures (50% of threshold) and were blocked by ICS
      205-930 (3 microM), but not ondansetron (5 microM). This novel finding suggests
      strongly that the prokinetic action of renzapride and gut motility stimulating
      action of 5-hydroxytryptamine are mediated via agonism at the putative 5-HT4
      receptor.

PMID- 1364819
TI  - Coronary vasoconstriction in the conscious rabbit following intravenous infusion
      of L-NG-nitro-arginine.
AB  - Intravenous infusion of L-NG-nitro-arginine, an inhibitor of endothelial nitric
      oxide (NO) synthesis, produced vasoconstriction in the coronary, cerebral, renal
      and duodenal vascular beds of the conscious rabbit. In this study, using
      radiolabelled microspheres, we provide in vivo evidence for a basal NO-dependent
      vasodilator tone in the coronary vascular bed.

PMID- 1364821
TI  - Prejunctional prostanoid receptors on cardiac adrenergic terminals belong to the
      EP3 subtype.
AB  - 1. The effects of prostaglandin E2 (PGE2) and of several synthetic prostanoids on
      the cardiac response to sympathetic nerve stimulation in guinea-pig atria have
      been evaluated. 2. PGE2 (0.01-100 nM), sulprostone (0.01-100 nM) and misoprostol
      (0.1-100 nM), but not butaprost (0.1-100 nM), dose-dependently reduced the
      increase in cardiac contractility induced by electrical field stimulation of
      sympathetic terminals. 3. The EP1 antagonist AH6809 (1 microM) did not modify the
      inhibition of cardiac response induced by PGE2, sulprostone and misoprostol. 4.
      In preparations preloaded with [3H]-noradrenaline, tritium overflow induced by
      electrical field stimulation was greatly and significantly reduced by 100 nM PGE2
      and by 100 nM sulprostone. 5. These results indicate that PGE2 and other
      synthetic prostanoids reduce noradrenaline release from cardiac adrenergic nerve
      terminals acting on prejunctional inhibitory receptors belonging to the EP3
      subtype.

PMID- 1364820
TI  - Relaxation of sheep cerebral arteries by vasoactive intestinal polypeptide and
      neurogenic stimulation: inhibition by L-NG-monomethyl arginine in endothelium
      denuded vessels.
AB  - 1. Perivascular nerves of the sheep middle cerebral artery show immunoreactivity
      for both vasoactive intestinal polypeptide (VIP) and calcitonin gene-related
      peptide (CGRP). 2. Rings of endothelium-denuded sheep middle cerebral artery
      precontracted with 5-hydroxytryptamine were relaxed by CGRP (maximum relaxation =
      87.8 +/- 8.1%, pD2 = 7.81 +/- 0.12, n = 12) and by VIP (maximum relaxation = 55.1
      +/- 4.1%, pD2 = 7.65 +/- 0.04, n = 18). Rings of endothelium-denuded cat middle
      cerebral artery precontracted with U46619 were also relaxed by vasoactive
      intestinal polypeptide (maximum relaxation = 53.1 +/- 6.1%, pD2 = 7.82 +/- 0.11,
      n = 6). 3. Haemolysate (1 microliters ml-1) inhibited VIP-induced relaxation in
      endothelium-denuded sheep and cat middle cerebral artery (n = 6) but had no
      effect on the CGRP-induced relaxation of the sheep middle cerebral artery (n =
      6). 4. The relaxant response to VIP in endothelium-denuded sheep middle cerebral
      artery was inhibited by methylene blue (10 microM) and augmented by either M&B
      22948 (10 microM) or superoxide dismutase (150 units ml-1). Indomethacin (1
      microM) had no effect. 5. The addition of L-NG-monomethyl arginine (100 microM)
      inhibited both neurogenic and VIP-induced relaxation of endothelium-denuded sheep
      MCA by 56 +/- 6% and 60 +/- 6% (n = 5) respectively. The CGRP-induced relaxation
      was unaffected. 6. It is concluded that neurally mediated vasodilatation in the
      sheep middle cerebral artery is mediated largely by VIP through a direct action
      on smooth muscle through a cyclic-GMP-mediated mechanism that appears to involve
      synthesis of nitric oxide from L-arginine. Vasodilatation by CGRP, which is also
      contained in perivascular nerves, does not utilize this pathway.

PMID- 1364822
TI  - Relationship between lipolysis and cyclic AMP generation mediated by atypical
      beta-adrenoceptors in rat adipocytes.
AB  - 1. The nature of the beta-adrenoceptor(s) mediating adenylyl cyclase activation
      in rat adipocyte ghosts by (-)-isoprenaline and the lipolytically selective beta
      adrenoceptor agonist, BRL 37344, was investigated by use of the beta 1-selective
      antagonist, CGP 20712A. The results were compared with lipolysis in adipocytes.
      2. While in lipolysis BRL 37344 was a full and 10 times more potent agonist than
      (-)-isoprenaline, in adenylyl cyclase activation similar pD2 values for both
      agonists were found. BRL 37344 was only a partial agonist on rat adipocyte
      adenylyl cyclase, with an intrinsic activity of 0.62. 3. With CGP 20712A small
      rightward shifts of the (-)-isoprenaline concentration-response curve (CRC) were
      observed at concentrations up to 10 microM, while at 100 microM and 1 mM clear
      rightward shifts occurred. The BRL 37344 CRC was not shifted with antagonist
      concentrations up to 10 microM. Only at 100 microM and 1 mM CGP 20712A were
      rightward shifts observed. 4. CGP 20712A concentrations of 10 microM and 100
      microM depressed the maximum of the (-)-isoprenaline CRC to 89 and 60%, while the
      BRL 37344 CRCs retained the control maximum effect (62% of (-)-isoprenaline).
      Only at 1 mM CGP 20712A, was the CRC of BRL 37344 depressed, while the (-)
      isoprenaline maximum was diminished further. 5. It was concluded that as with
      lipolysis, (-)-isoprenaline acts both through typical beta 1- and atypical beta 3
      adrenoceptors for activation of adenylyl cyclase, while BRL 37344 acts solely
      through atypical beta 3-adrenoceptors. 6. The results also demonstrate that the
      relationship between adenosine 3':5'-cyclic monophosphate (cyclic AMP) and
      lipolysis is different for BRL 37344 and (-)-isoprenaline. Although the maximum
      activation of adenylyl cyclase by BRL 37344 is only 62% of that by (-)
      isoprenaline, the distance between the lipolysis and adenylyl cyclase CRCs is
      much larger in the case of BRL 37344, indicating a larger transduction reserve
      for this agonist.

PMID- 1364823
TI  - Selective and competitive antagonism by suramin of ATP-stimulated catecholamine
      secretion from PC12 phaeochromocytoma cells.
AB  - 1. Suramin, a putative P2-antagonist, (10 to 300 microM) inhibited the adenosine
      5'-triphosphate (ATP)-stimulated secretion of [3H]-noradrenaline or endogenous
      dopamine from phaeochromocytoma PC12 cells in a concentration-dependent manner.
      Suramin (300 microM) did not affect the dopamine-secretion stimulated by high K+
      or nicotine. 2. Suramin shifted the concentration-response curve for ATP to the
      right. The antagonism was competitive with a pA2 value of 4.52. 3. ATP also
      stimulated an increase in intracellular Ca2+ concentration as determined by fura
      2 methods. Suramin antagonized this effect over the same concentration range that
      antagonized the ATP-stimulated catecholamine secretion. 4. These results suggest
      that suramin can be used as a selective and competitive antagonist of ATP in
      experiments concerning mechanisms of catecholamine-secretion.

PMID- 1364824
TI  - Local application of drugs to sympathetic nerve terminals: an
      electrophysiological analysis of the role of prejunctional alpha-adrenoceptors in
      the guinea-pig vas deferens.
AB  - 1. Focal extracellular recording techniques were used to study the effects of
      clonidine, yohimbine and tyramine on the intermittent transmitter release
      mechanism in the guinea-pig vas deferens in vitro. Drugs were applied locally to
      the varicosities located within the recording electrode. Statistical methods were
      used to determine whether noradrenaline (NA) acts locally to inhibit secretion
      from the same or a closely related release site (local regulation) on an impulse
      to-impulse basis. 2. The alpha-adrenoceptor agonist, clonidine, inhibited
      transmitter release, an effect reversed by the alpha-adrenoceptor antagonist,
      yohimbine. Yohimbine alone increased action potential-evoked transmitter release,
      findings consistent with the idea that transmitter release is regulated through
      prejunctional alpha-adrenoceptors. 3. The indirectly acting sympathomimetic,
      tyramine, powerfully inhibited evoked transmitter release, an effect reversed by
      both yohimbine and phentolamine. The inhibitory effects of tyramine were greatly
      reduced in tissues taken from animals pretreated with reserpine. Clonidine
      powerfully inhibited transmitter release in reserpinized tissues showing that
      prejunctional alpha-adrenoceptors were functionally intact. The inhibitory
      effects of tyramine on transmitter release are therefore mediated indirectly
      through the release of endogenous NA. 4. Paradoxically, when transmitter release
      from a small population of variscosities on a single nerve fibre was studied in
      the absence of alpha-adrenoceptor antagonists, no evidence was found for local
      regulation of transmitter release. 5. The intermittent character of the
      transmitter release process makes it difficult to envisage how impulse-to-impulse
      regulation could occur. Furthermore, it is unlikely that NA will accumulate to
      any appreciable extent in the vicinity of the secreting varicosity. 6. The
      pharmacological evidence clearly supports the view that NA released from
      sympathetic nerve terminals by nerve impulses modulates subsequent transmitter
      release. However, the evidence does not support the view that released NA acts
      locally to inhibit secretion from recently activated varicosities.

PMID- 1364825
TI  - Beneficial effects of N-acetylcysteine and cysteine in stunned myocardium in
      perfused rat heart.
AB  - 1. The objective of this study was to evaluate the effects of three sulphydryl
      (SH) compounds, N-acetylcysteine (NAC), cysteine (Cys) and cystamine, on
      functional recovery and ventricular arrhythmias (VF) in stunned myocardium in the
      isolated perfused heart of the rat. 2. Hearts (n = 7-8 per group) were perfused
      by the Langendorff procedure for 20 min to stabilize and then assigned to one of
      five groups: saline, sham, NAC, Cys and cystamine. After the stabilizing period,
      the drugs (at 3.6 microM min-1) or their vehicle (saline) were infused into
      coronary vessels throughout the experimental period. Ten min after administration
      of drugs, the left anterior descending coronary artery (LAD) was ligatured for 20
      min and then untied to reperfuse for 30 min. In the sham group, a ligature was
      placed around the LAD but not tied. 3. NAC and Cys had a significant effect in
      attenuating myocardial stunning: the percentage recovery of rate-pressure product
      measured 30 min after reperfusion as an index of heart function, was improved
      with the NAC (98.3 +/- 4.5) and Cys groups (104.0 +/- 6.5) compared with the
      saline (only 73.6 +/- 3.8, P < 0.01) group. Cystamine did not show these
      beneficial effects. This may be due to the difference in chemical structure
      between NAC, Cys and cystamine since the latter does not have a free SH group
      with a disulphide bond formed. This phenomenon suggests that a free SH group is
      essential for the protective effects of compounds like NAC and Cys in myocardial
      injury. 4. NAC and Cys prevented the fall in coronary flow during the LAD
      occlusion and enhanced coronary flow during reperfusion but cystamine did not
      have such a beneficial effect. 5. The incidence of VF in the saline, cystamine,
      Cys and NAC groups was 6/8 (75.0%), 4/7 (57.1%), 3/8 (37.5%) and 2/7 (28.6%),
      respectively, and no significant differences (P > 0.05) were noted between the
      saline- and drug-treated groups. 6. An in vitro study with electron spin
      resonance indicated that Cys effectively scavenged the hydroxyl radical (-OH)
      generated by Fenton's reaction but did not scavenge superoxide generated in an
      irradiated riboflavin system. NAC and cystamine showed a scavenging effect on -OH
      to a certain extent but this effect did not reach statistical significance (P >
      0.05 vs saline). 7. Our results demonstrate that NAC and Cys treatment before
      ischaemia and reperfusion can reduce myocardial stunning. This beneficial effect
      may be mainly due to their ability to preserve and enhance coronary flow during
      coronary occlusion and reperfusion and in part due to scavenging -OH and/or
      replenishing intracellular glutathione. The results also indicate that the
      condition of coronary perfusion can produce a great impact on postischaemic
      ventricular performance.

PMID- 1364826
TI  - Heterogeneity of thromboxane A2 (TP-) receptors: evidence from antagonist but not
      agonist potency measurements.
AB  - 1. Thromboxane A2 (TP-) receptors in human, rat and rabbit platelets and in
      smooth muscle of guinea-pig trachea, rat aorta and rabbit aorta have been
      characterized by measurement of the potencies of agonists and antagonists having
      considerable variations in chemical structure. 2. On each washed platelet system,
      eight prostanoids induced maximal irreversible aggregation (full agonists) and
      the potency ranking was EP 171 > STA2 > 9,11-azo PGH2 > 9,11-endoxy-10a-homo PGH2
      > U-46619 (standard) > PGH2 = 16-p-fluorophenoxy-omega-tetranor PGF2 alpha >
      16,16-dimethyl PGF2 alpha. Correlations between the three platelet preparations
      for both absolute and relative potencies were good. On human platelets, STA2, at
      concentrations above that required for maximum aggregation, exerted an inhibitory
      effect which was independent of its interaction with the TP-receptor. 3. Five
      prostanoids, EP 109, EP 167, EP 204, PTA2 and 16,20-methano PTA2, exhibited
      partial agonist activity on the platelet and smooth muscle preparations. There
      was good agreement between absolute potencies on the six preparations; on
      platelets potency was assessed from shape change measurements, since aggregation,
      when present, always showed a very shallow concentration-response relationship.
      The magnitude of the maximum response induced by each compound decreased in the
      order listed above, to the extent that 16,20-methano PTA2 could be treated as a
      pure antagonist. 4. With U-46619 as agonist, the pA2 values of seven antagonists
      were found to be very similar on human and rat platelets. The potency ranking was
      EP 169 > AH 23848 > EP 092 > ONO 11120 > EP 115 = 16,20-methano PTA2 > BM 13177.
      There was a similar trend on rabbit platelets but pA2 values were 1.0-1.5 log
      units smaller; the exception was BM 13177 which had similar affinities. The
      antagonism produced by EP 169 and AH 23848 was surmountable on rabbit platelets
      but not on human and rat platelets. 5. None of the antagonists was highly potent
      on the rabbit aorta (pA2 values < 7.5 by Schild analysis). Affinities on the
      guinea-pig trachea and the rat aorta were higher and in the same range as those
      obtained for human and rat platelets. However the correlations of pA2 values
      between any pair of smooth muscle preparations and between any pair of
      platelet/smooth muscle preparations were either weak or not significant(P >
      0.05). 6. The excellent agreement for both full and partial agonist potencies
      between the six preparations provides no evidence for TP-receptor subtypes and
      further suggests that the agonist recognition sites of the TP-receptors could be
      very similar, if not identical, in nature. In contrast, the different antagonist
      affinities found in this and other published studies indicate heterogeneity of TP
      receptors. However, classification into TP,-, TP2-receptors, etc. on the basis of
      the limited antagonist data available does not appear appropriate at this time.

PMID- 1364827
TI  - Evidence that the 5-HT3 receptors of the rat, mouse and guinea-pig superior
      cervical ganglion may be different.
AB  - 1. Using grease-gap recordings from the isolated superior cervical ganglion of
      mouse, rat and guinea-pig, we have compared the depolarization evoked by 5
      hydroxytryptamine (5-HT) with that evoked by the selective 5-HT3 receptor agonist
      2-methyl-5-HT (2-Me-5-HT). 2. The maximum depolarization induced by 2-Me-5-HT was
      smaller than that induced by 5-HT in all three species, and particularly in the
      guinea-pig. 3. The 5-HT2 receptor antagonist ketanserin (1 microM) caused a clear
      rightward shift of the dose-response curve to 5-HT on the guinea-pig ganglion,
      but not on the mouse or rat ganglion. Spiperone (0.03 microM) had a
      quantitatively similar action to ketanserin (0.1 microM) on the 5-HT dose
      response curve of the guinea-pig ganglion. Ketanserin had no significant effect
      on the dose-response curve to 2-Me-5-HT on any of these ganglia. 4. Using 2-Me-5
      HT as the agonist, we determined the pA2 values for two 5-HT3 receptor
      antagonists. The potency of ICS 205-930 varied by approximately 100 fold between
      the species and that of (+)-tubocurarine varied by over 1000 fold. The
      differences in the pA2 values of these compounds varied independently among the
      species. 5. We conclude that 5-HT3 receptors are present on the superior cervical
      ganglion from the rat, mouse and guinea-pig, but these receptors may be
      pharmacologically distinct from each other. In addition, the depolarization of
      the guinea-pig superior cervical ganglion by low concentrations of 5-HT is
      largely mediated by ketanserin-sensitive receptors.

PMID- 1364828
TI  - Effects of vasoactive intestinal peptide (VIP) on contractile responses of smooth
      muscle in rat stomach.
AB  - 1. The effects of vasoactive intestinal peptide (VIP) on contractile responses to
      carbachol (CCh), KCl and caffeine of the circular smooth muscle in rat stomach
      were examined by the isometric tension recording method and by measurement of the
      intracellular Ca level, [Ca]i, with fura 2. 2. Removal of extracellular Ca or
      nifedipine (0.1 microM) inhibited contractions induced by KCl (40 mM) and a low
      concentration (1 microM) of CCh but not that induced by caffeine (3 mM). After
      these treatments, the contraction induced by a high concentration of CCh (100
      microM) changed to a phasic response. 3. VIP dose-dependently inhibited the
      contraction induced by 1 microM CCh, but not those caused by 40 mM KCl or 3 mM
      caffeine. 4. In Ca-free solution containing 2 mM EGTA, VIP inhibited the phasic
      contraction induced by 100 microM CCh, but not that induced by 30 mM caffeine. 5.
      CCh caused dose-dependent tension development concomitant with the increase in
      [Ca]i. VIP reduced both responses and thus did not affect the [Ca]i-force
      relation for CCh. In the chemically skinned muscle fibres, VIP had no effect on
      the pCa-tension relation. 6. It is suggested that the inhibitory effects of VIP
      on CCh-induced contractions are due to the inhibition of the processes of signal
      transduction from muscarinic receptors to voltage-dependent Ca channels and to
      intracellular Ca stores.

PMID- 1364829
TI  - Adenosine-5'-O-(2-thiodiphosphate) is a potent agonist at P2 purinoceptors
      mediating insulin secretion from perfused rat pancreas.
AB  - 1. The effects of a P2 purinoceptor agonist, adenosine 5'-O-(2-thiodiphosphate)
      (ADP-beta-S) have been studied on insulin secretion and flow rate of the isolated
      perfused pancreas of the rat. 2. In the presence of a moderately stimulating
      glucose concentration (8.3 mM), ADP-beta-S (4.95-495 nM) evoked a biphasic
      insulin response in a concentration-dependent manner. A comparison of relative
      potency between ADP-beta-S and adenosine 5'-triphosphate (ATP) showed that ADP
      beta-S was 100 times more potent than ATP. On the other hand, in the presence of
      a non stimulatory glucose concentration (4.2 mM), ADP-beta-S (165 nM) did not
      modify the basal insulin secretion. 3. ADP-beta-S, at concentrations effective on
      insulin secretion and also at higher concentrations (1.65 and 16.5 microM),
      provoked an increase of the pancreatic flow rate in a concentration-dependent
      manner. 4. Our results show that ADP-beta-S is a potent insulin secretory P2
      purinoceptor agonist. As it is resistant to hydrolysis it might be useful in
      studying the effect of activation of the P2 purinoceptor of beta cells on insulin
      secretion in vivo.

PMID- 1364830
TI  - A comparison of the relative activities of a number of GABAB antagonists in the
      isolated vas deferens of the rat.
AB  - 1. A series of GABAB receptor antagonists were tested against (+/-)-baclofen for
      activity on the presynaptic GABAB receptor in the rat vas deferens. 2. All the
      antagonists tested caused a rightward shift in the concentration-response curve
      to (+/-)-baclofen. 3. pA2 values calculated from full Schild analysis were as
      follows: phaclofen, pA2 = 4.3; delta-amino valeric acid, pA2 = 4.4; 3
      aminopropyl(diethoxymethyl)phosphinic acid (CGP 35348), pA2 = 5.0; 3-amino
      propyl(n-hexyl)phosphinic acid (3-APHPA), pA2 = 4.5. 4. These results show that
      none of the above compounds possess potent antagonist activity at the GABAB
      receptor (i.e. pA2 > 6) in this peripheral tissue. In addition, the more recently
      available phosphinic acid antagonists, appear to offer no great advance over the
      GABAB antagonists previously available.

PMID- 1364831
TI  - Pharmacology of a cholecystokinin receptor on 5-hydroxytryptamine neurones in the
      dorsal raphe of the rat brain.
AB  - 1. The effect of bath application of sulphated cholecystokinin octapeptide (CCK
      8) was studied on neurones in slices containing rat raphe nucleus. 2.
      Intracellular recordings were made from neurones in the dorsal raphe nucleus.
      Some of the neurones with the characteristics of 5-hydroxytryptamine (5-HT)
      containing cells which were inhibited by 5-HT and excited by noradrenaline were
      excited by cholecystokinin. The response to cholecystokinin was dose-dependent
      over the range 10 to 1000 nM. 3. The response to CCK-8 persisted in the presence
      of tetrodotoxin. Either reduction of extracellular calcium or addition of 25 mM
      magnesium did not block the CCK response, suggesting it was mediated by receptors
      located on the membrane of the raphe neurones. 4. The agonist and antagonist
      specificity of the CCK response was determined. The CCKB selective agonist,
      pentagastrin, was inactive when applied at concentrations up to 10 microM. the
      CCKA receptor antagonist L-364,718 (1 to 100 nM) blocked the response to
      cholecystokinin. Much higher (1-10 microM) concentrations of the CCKB receptor
      antagonist L-365,260 were required for inhibition of the CCK response. 5. These
      data support the existence of a CCK receptor, located on raphe neurones in the
      rat, with a pharmacological profile very similar to that described for the CCKA
      type.

PMID- 1364832
TI  - The pressor response to central administration of beta-endorphin results from a
      centrally mediated increase in noradrenaline release and adrenaline secretion.
AB  - 1. The effects of intracerebroventricular (i.c.v.) and intracisternal (i.c.)
      administration of beta-endorphin (0.01, 0.1 and 1.0 nmol kg-1) were examined in
      conscious rabbits. 2. After i.c.v. beta-endorphin, mean arterial pressure (MAP)
      increased, heart rate (HR) fell, plasma noradrenaline, adrenaline and glucose
      increased and there was a rise in PaCO2 and fall in PaO2; these effects were
      reversed by intravenous (i.v.) naloxone (300 nmol kg-1). 3. A combination of
      prazosin (2 mg kg-1) and yohimbine (1 mg kg-1), given i.v., prevented the rise in
      MAP induced by i.c.v. beta-endorphin. 4. After i.c. beta-endorphin, MAP, HR and
      plasma catecholamines were not significantly altered but there was a similar
      degree of respiratory depression. 5. Clonidine (1.0 micrograms kg-1, i.c.)
      reduced MAP and HR; these effects were not blocked by i.v. naloxone (6 mumol kg
      1). 6. These results demonstrate that beta-endorphin acts centrally, probably
      mainly on periventricular mu-opioid receptors, to increase adrenaline secretion
      and sympathetic nerve activity leading to alpha-adrenoceptor-mediated
      vasoconstriction. The respiratory depression is probably mediated by brainstem mu
      receptors. 7. A role for beta-endorphin in the central hypotensive action of
      alpha 2-adrenoceptor agonists was opposed by finding that opioid receptor
      antagonism with naloxone did not block the effects of clonidine.

PMID- 1364833
TI  - The effects of adenosine triphosphate (ATP) and related purines on human isolated
      subcutaneous and omental resistance arteries.
AB  - 1. Human resistance arteries were obtained from specimens of omentum and
      subcutaneous fat removed at surgery. They were studied in vitro by use of a
      myograph technique to determine the effects of purines on the arteries. 2. In
      preparations where tone had been raised with noradrenaline, low concentrations (1
      nM-1 microM) of adenosine triphosphate (ATP) and 2-methylthioATP, but not
      alpha,beta-methyleneATP, produced concentration-dependent relaxation. There was a
      lack of relationship between the relaxation response to acetylcholine and that to
      ATP. 3. In preparations under basal tone, high concentrations (1 microM-1 mM) of
      ATP, 2-methylthioATP and alpha,beta-methyleneATP produced concentration-dependent
      contractions. 4. The rank order of potency of the purine nucleotide analogues for
      the relaxation response was 2-methylthioATP > ATP > alpha,beta-methyleneATP and
      for the contractile response it was alpha,beta-methyleneATP > ATP = 2
      methylthioATP. 5. Adenosine produced concentration-dependent relaxation in
      preparations under raised tone and was less potent than ATP but did not produce
      contraction in preparations at basal tone. Relaxation responses to adenosine, but
      not to ATP, were antagonized by 8-phenyltheophylline. 6. These results indicate
      the presence of vasodilator P2y- and P1-purinoceptors and vasoconstrictor P2x
      purinoceptors on human resistance arteries isolated from omental and subcutaneous
      sites.

PMID- 1364834
TI  - Block of cardiac sodium channels by amiodarone studied by using Vmax of action
      potential in single ventricular myocytes.
AB  - 1. Acute effects of amiodarone on cardiac sodium channels were investigated in
      ventricular myocytes isolated from guinea-pig hearts, and compared with those of
      lignocaine. 2. Transmembrane potential was recorded and controlled by whole-cell
      current-clamp and voltage-clamp respectively through suction pipette electrodes.
      The maximum upstroke velocity (Vmax) of the action potential was used as a
      qualitative index of sodium channel availability. 3. In myocytes treated with
      amiodarone (1 microM) or lignocaine (40 microM), Vmax of reference action
      potential elicited at 0.03 Hz was decreased by 6-11%, indicating minimal tonic
      block of sodium channels. 4. Application of a single conditioning depolarization
      to those myocytes resulted in a significant decrease in Vmax of a subsequent test
      action potential. The Vmax reduction was enhanced in a single exponential
      function as the clamp pulse duration was prolonged. Time constants at 0 mV clamp
      were 25 ms for amiodarone and 122 ms for lignocaine. 5. Vmax recovery of test
      action potential following a 1000 ms 0 mV clamp was approximated by a dual
      exponential function. Time constants for the late slow component (tau R) at the
      resting potential level were 418 ms for amiodarone and 178 ms for lignocaine. tau
      R values were shortened in a voltage-dependent manner by hyperpolarization during
      the coupling interval. 6. These findings suggested that amiodarone, like
      lignocaine, blocks the sodium channel primarily when it is in the inactivated
      state. Both onset and offset kinetics of the block are very rapid. Such sodium
      channel blocking characteristics may contribute to its potent antiarrhythmic
      activity.

PMID- 1364835
TI  - The use of 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine (4-DAMP mustard) for
      estimating the apparent affinities of some agonists acting at muscarinic
      receptors in guinea-pig ileum.
AB  - 1. 4-Diphenylacetoxy-N-(2-chloroethyl)-piperidine (4-DAMP mustard), which is
      known to block muscarinic M3 receptors in preference to muscarinic M2 receptors,
      was used to estimate the apparent affinity constants of some agonists acting at
      muscarinic receptors in guinea-pig ileum. Estimates for carbachol and n-pentyl
      trimethyl ammonium iodide were similar to published values obtained in similar
      conditions: those for n-hexyl-trimethyl ammonium iodide were slightly lower. 2.
      The results for the agonists, n-pentyl- and n-hexyl-trimethyl ammonium iodides
      and for the partial agonist, n-heptyl-trimethyl ammonium iodide were not as
      regular as was suggested by Stephenson, though there is an overall increase in
      apparent affinity with chain length. 3. Estimates of apparent affinity may be
      affected by hexamethonium, usually present in experiments on ileum. Its absence
      had little effect on the results with carbachol but reduced the estimates
      obtained with n-pentyl trimethyl ammonium, which has strong nicotinic effects
      compared with its muscarinic effects. On ileum treated with tetrodotoxin the
      values for n-pentyl trimethyl ammonium were similar to those obtained in the
      presence of hexamethonium (0.28 mM): slightly higher estimates of affinity were
      obtained in the presence of indomethacin (2.8 microM). The nicotinic effects of n
      pentyl ammonium may involve the release of prostaglandins. 4. The estimates of
      apparent affinity did not depend on the method used to calculate them as the
      'null' method and the 'operational' method give similar answers. Estimates of the
      transducer-ratio for the partial agonist, n-heptyl-trimethyl ammonium iodide,
      were numerically the same as those of its efficacy. 5. This work illustrates the
      use of 4-DAMP mustard as a tool for measuring the apparent affinity of agonists
      acting at muscarinic M3 receptors.

PMID- 1364836
TI  - Pharmacokinetic-pharmacodynamic modelling of the EEG effects of midazolam in
      individual rats: influence of rate and route of administration.
AB  - 1. The purpose of the present investigation was to quantify the concentration
      pharmacological effect relationship of midazolam in individual rats by use of
      effect parameters derived from aperiodic EEG analysis. By varying the rate and
      route of administration the role of (inter)active metabolites and development of
      acute tolerance was evaluated. 2. The pharmacokinetics and pharmacodynamics of
      midazolam were determined after intravenous administration of 10 mg kg-1 during
      5, 30 and 60 min and oral administration of 15 mg kg-1. Following intravenous
      administration the pharmacokinetics were most adequately described by a bi
      exponential equation. The values (mean +/- s.e. mean, n = 20) of clearance,
      volume of distribution at steady-state and terminal half-life were 67 +/- 2 ml
      min-1 kg-1, 1.61 +/- 0.071 kg-1 and 27 +/- 1 min, respectively. Following oral
      administration midazolam was rapidly absorbed with a systemic availability of 45
      +/- 9%. 3. The averaged amplitudes in the 11.5-30 Hz (beta) frequency band of the
      fronto-central lead on the left-hemisphere, as derived by aperiodic EEG analysis,
      was selected as a measure of the pharmacological effect of midazolam. By
      pharmacokinetic-pharmacodynamic modelling the individual concentration-EEG effect
      relationships of midazolam were derived, which were successfully quantified by
      the sigmoidal Emax model. No marked and systematic differences in pharmacodynamic
      parameters were found between the rates and routes of administration. The
      averaged pharmacodynamic parameters of midazolam obtained after combining the
      results of all rates and routes of administration were (mean + s.e.mean, n = 27):
      Eo = 61 + 3puV s 1, Emax = 85 + 3 Vs 1, EC50 = 40 + 3 ngmlP-1 and N = 0.84 +
      0.04. 4. The results of the present study show that the concentration-EEG effect
      relationship of midazolam can be characterized in individual animals using the
      amplitudes in the 11.5-30 (beta) frequency band as a measure of pharmacological
      response. Acute tolerance did not develop and (inter)active metabolites did not
      contribute to this effect parameter within the time span of the experiments.

PMID- 1364837
TI  - The effects of the stereoisomers of propafenone and diprafenone in guinea-pig
      heart.
AB  - 1. Optically pure enantiomers of propafenone and diprafenone were prepared from
      their racemic mixtures and tested for their ability to block beta-adrenoceptors
      and to prolong functional refractory period in the guinea-pig heart. beta
      Adrenoceptor affinity of the enantiomers was determined by the radioligand
      binding technique and in functional experiments. 2. Propafenone and diprafenone
      inhibited specific binding of the beta-adrenoceptor antagonist (-)-[3H]-CGP-12177
      to guinea-pig myocardial membranes. beta-Adrenoceptor affinities of diprafenone
      enantiomers exceeded those of corresponding propafenone enantiomers by one order
      of magnitude. Displacement of (-)-[3H]-CGP-12177 by both antiarrhythmics was
      highly stereoselective, in that the (S)-enantiomers were 40-60 fold, i.e. 1.6-1.8
      log units more potent than the (R)-enantiomers. 3. Propafenone and diprafenone
      antagonized the positive inotropic action of isoprenaline in isolated atria. beta
      Adrenoceptor antagonist potencies of diprafenone enantiomers were about one order
      of magnitude higher than those of corresponding propafenone enantiomers. For both
      drugs the (S)-enantiomer was found to be considerably more potent (14-40 fold)
      than the (R)-enantiomer. 4. Propafenone and diprafenone prolonged functional
      refractory period of isolated auricles with equal potency and no difference in
      the antiarrhythmic activity of purified enantiomers was found. 5. It is concluded
      that the enantiomers of propafenone and diprafenone exert comparable
      antiarrhythmic activity, whereas only (S)-enantiomers block cardiac beta
      adrenoceptors with high affinity, which explains the beta-adrenoceptor antagonist
      effects of the racemic drugs.

PMID- 1364838
TI  - Differential effect of R 56865 on ouabain binding to isolated sarcolemma and
      intact atrial tissue of guinea-pig.
AB  - 1. R 56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl]-N-methyl- 2
      benzothiazolamine) is a compound known to antagonize cardiac glycoside
      intoxication. Therefore, the effect of the compound on ouabain binding to intact
      cardiac tissue as well as cardiac membrane preparations was investigated. 2. The
      binding of ouabain to highly purified sarcolemmal membranes was not influenced by
      R 56865 1 x 10(-6) mol l-1 (ouabain: KD = 1.3 x 10(-7) mol l-1, Bmax = 160 pmol
      mg-1; ouabain + R 56865: KD = 1.4 x 10(-7) mol l-1, Bmax = 168 pmol mg-1). 3. In
      contrast to the results in purified membranes, the binding of ouabain (10(-8) mol
      l-1 to 5 x 10(-7) mol l-1) to intact atria was significantly reduced. 4. Ouabain,
      5 x 10(-7) mol l-1, led to a transient positive inotropic effect of about 220%
      followed by a developing negative inotropic effect after 3 h. R 56865, 10(-7) mol
      l-1, led to a maximal positive inotropic effect of about 290% also followed by a
      delayed decline of contractile force. A tenfold higher concentration of R 56865
      led to sustained positive inotropic effect of about 250% in the same time
      interval. 5. The different effects of R 56865 on ouabain binding in subcellular
      preparations and intact tissue do not support the view that R 56865 interferes
      directly with the action of ouabain on Na/K-ATPase. An indirect effect, which may
      be mediated by a lowered intracellular sodium load is discussed.

PMID- 1364839
TI  - Comparison of the effects of several potassium-channel openers on rat bladder and
      rat portal vein in vitro.
AB  - 1. The ability of several K-channel openers to inhibit KCl-induced contractions
      of rat bladder detrusor and spontaneous mechanical activity in rat portal vein
      was examined. 2. Lemakalim, pinacidil, Ro 31-6930, RP 49356, P1060 and S 0121
      dose-dependently relaxed rat detrusor, precontracted with 20 mM KCl. With the
      exception of pinacidil, concentrations of these agents below 30 microM did not
      inhibit 80 mM KCl-included contractions. Pinacidil (10 microM) produced a small,
      but significant (P < 0.05) relaxation of 80 mM KCl-induced mechanical activity.
      Minoxidil sulphate and BRL 38226 produced some relaxation of 20 mM but not 80 mM
      KCl-induced contractions. 3. Glibenclamide (0.3-3 microM) antagonized the
      relaxant effects of lemakalim, pinacidil, Ro 31-6930, RP 49356, P1060 and S 0121
      in a competitive manner (pA2 values 6.3-6.6). The effects of minoxidil sulphate
      and BRL 38226 were fully antagonized by 3 microM glibenclamide. 4. Lemakalim,
      pinacidil, S 0121, BRL 38226 and minoxidil sulphate were each approximately 8
      times more potent as inhibitors of the spontaneous contractions of rat portal
      vein than KCl-induced contractions of the rat detrusor. Minoxidil sulphate was
      approximately 30 times more potent in the rat portal vein than in the bladder.
      This may indicate that either minoxidil sulphate is acting at different
      recognition sites in these two tissues, or that this compound has an additional
      mechanism of action in the portal vein. 5. With the exception of minoxidil
      sulphate, all the compounds tested stimulated 86Rb efflux and 42K efflux from
      preloaded rat detrusor strips. The stimulated 86Rb efflux was qualitatively but
      not quantitatively similar to the stimulated 42K efflux. Minoxidil sulphate
      stimulated 42K efflux from rat portal vein but not from rat bladder. 6. It is
      concluded that all the compounds tested cause relaxation of rat detrusor
      predominantly by Kchannel opening. Selectivity for bladder rather than vascular
      smooth muscle was not shown by any compound.

PMID- 1364840
TI  - Anti-arrhythmic activities of opioid agonists and antagonists and their
      stereoisomers.
AB  - 1. A series of opioid agonists, antagonists and their (+)-stereoisomers were
      tested for antiarrhythmic activity in the rat coronary artery occlusion model. 2.
      Naloxone (0.01-2 mg kg-1) significantly reduced the incidence and severity of
      cardiac arrhythmias, in accordance with previous published studies. 3. The non
      opioid stereoisomer, (+)-naloxone, was equipotent with naloxone against occlusion
      induced arrhythmia. 4. Similar non-stereospecific antiarrhythmic effects were
      induced by another opioid antagonist, Win 44,441-3 and its stereoisomer Win
      44,441-2. 5. The opioid agonists, morphine and levorphanol, protected against
      occlusion-induced arrhythmia as did the opioid antagonists, and the (+)
      stereoisomer, dextrorphan, was equipotent to levorphanol. 6. It is concluded that
      the antiarrhythmic effects of opioid drugs are not mediated by opioid receptors.
      A direct effect on ionic currents in cardiac muscle is suggested as the mechanism
      of opioid antiarrhythmic activity.

PMID- 1364841
TI  - Effects of antagonists on quisqualate and nicotinic receptor-mediated currents of
      midbrain neurones in culture.
AB  - 1. The action of non-N-methyl-D-aspartate (non-NMDA) and nicotinic antagonists on
      excitatory postsynaptic currents (e.p.s.cs) and on quisqualate (Quis)- and
      nicotine-gated currents was studied by use of whole-cell recording in dissociated
      culture of the rat midbrain. 2. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX; 0.1
      microM) and kynurenic acid (0.1 mM) attenuated network-generated and miniature
      e.p.s.cs while mecamylamine (100 microM) and hexamethonium (400 microM) had no
      effect. Acetylcholine (ACh) enhanced or suppressed e.p.s.cs. The suppressing
      effect of ACh was blocked by atropine (0.1-10 microM). 3. ACh (50-1000 microM)
      and quisqualate (Quis, 0.1-20 microM) induced inward currents with the same
      reversal potential as e.p.s.cs. 4. Application of Quis and alpha-amino-3-hydroxy
      5-methylisoxazole-4-propionic acid (AMPA) in a low concentration (0.5 and 5
      microM, respectively) evoked a maintained current which was attenuated by CNQX (1
      microM) and kynurenic acid (0.5 mM) but not by mecamylamine (100 microM). 5.
      Higher concentrations of Quis (5-20 microM) and AMPA (50-100 microM) evoked a
      transient and a maintained current component. Kynurenic acid (1 mM) reduced the
      transient but not the maintained component. CNQX (5-10 microM) increased the
      maintained component without reducing the transient one; 20 microM CNQX reduced
      both components. 6. ACh-induced transient current was mimicked by nicotine and
      reversibly and dose-dependently blocked by mecamylamine. Atropine (10 microM),
      hexamethonium (400 microM) as well as CNQX (100 microM) and kynurenic acid (1 mM)
      did not affect the current. 7. Hexamethonium (50-400 microM) voltage-dependently
      depressed the maintained current elicited by both Quis and ACh. 8. In conclusion,
      although the antagonists examined here seem to discriminate between non-NMDA and
      nicotinic receptor-mediated e.p.s.cs, they vary considerably in respect of their
      mode of action when tested on Quis, AMPA and ACh-induced currents.

PMID- 1364842
TI  - Pharmacological evidence for the possible involvement of repetitive action
      potentials in facilitation by GABA of catecholamine secretion in bovine adrenal
      chromaffin cells.
AB  - 1. gamma-Aminobutyric acid (GABA) evokes catecholamine (CA) secretion and
      enhances the stimulation-evoked CA secretion via facilitation of Ca2+ entry in a
      Cl(-)-dependent manner. The present study was designed to investigate further the
      ionic mechanism of modulation by GABA of CA secretion from adrenal medulla, using
      a primary culture of bovine chromaffin cells. 2. Tetrodotoxin (TTX), a voltage
      sensitive Na+ channel blocker, reduced GABA-evoked CA secretion. 3. Inhibition of
      the sodium pump by ouabain or removal of extracellular K+ enhanced GABA-evoked CA
      secretion in a TTX-sensitive manner. 4. Tetraethylammonium (TEA) and cesium,
      which are known to block some types of K+ channels, markedly enhanced GABA-evoked
      CA secretion in a concentration-related fashion. TEA-induced enhancement of the
      GABA-evoked CA secretion was attenuated by TTX or replacement of extracellular
      Na+ by choline. On the other hand, ouabain accelerated the effect of TEA. 5. TEA
      and ouabain also enhanced GABA-induced Ca2+ influx and accumulation of cytosolic
      Ca2+, assessed with 45Ca2+ uptake and quin2 fluorescence. 6. Veratridine
      increased accumulation of cytosolic Ca2+ in a TTX-sensitive manner. GABA
      facilitated the veratridine-induced elevation of cytosolic Ca2+ even when the
      GABA-induced rise of cytosolic Ca2+ levelled off. 7. These results suggest the
      involvement of repetitive action potentials in modulation of GABA by Ca2+
      mobilization and, as a consequence, of the CA secretion in chromaffin cells.

PMID- 1364843
TI  - Changes in neurotransmitter sensitivity in the mouse neocortical slice following
      propranolol and theophylline administration.
AB  - 1. The mouse neocortical slice has been used to examine the sensitivity of
      neurones to isoprenaline, 5-hydroxytryptamine (5-HT) and adenosine acutely and
      following chronic treatment of animals with propranolol or theophylline. 2. While
      having little effect alone, all three agonists enhanced the d.c. depolarizing
      potential produced by N-methyl-D-aspartate (NMDA). The effect of (-)-isoprenaline
      (0.2 microM) was shared by (+)-isoprenaline at the much higher concentration of
      10 microM. 3. Superfusion of slices with theophylline or 8-phenyltheophylline
      blocked responses to adenosine with evidence of selectivity. A single injection
      of theophylline 24 h before slice preparation did not alter agonist sensitivity,
      but when administered daily at 100 mg kg-1 for 14 days, the xanthine caused a
      loss of sensitivity to adenosine and (-)-isoprenaline but not 5-HT. The lower
      dose of theophylline, 10 mg kg-1 daily, also led to a loss of adenosine responses
      but no change of sensitivity to the amines. 4. Following the 14 day treatment
      with theophylline at 100 mg kg-1 daily in two groups of mice, responses to
      adenosine recovered to control levels after 20 days. 5. Propranolol superfusion
      blocked responses to both isomers of isoprenaline and 5-HT but did not affect
      sensitivity to adenosine. 6. Chronic treatment with propranolol at 25 mg kg-1
      daily for 14 days induced a loss of sensitivity to (-)-isoprenaline and 5-HT but
      not adenosine. A lower dose of 5 mg kg-1 daily caused no change in responses to
      adenosine or 5-HT, but yielded an increased sensitivity to (-)-isoprenaline. 7.
      The results are discussed with respect to reports of receptor up-regulation in
      binding studies; caution is clearly required in extrapolating from such work to
      receptor activity in a functional system, especially in the case of theophylline
      and adenosine.

PMID- 1364844
TI  - Alkylation with beta-funaltrexamine suggests differences between mu-opioid
      receptor systems in guinea-pig brain and myenteric-plexus.
AB  - 1. The effects of pre-incubation with beta-funaltrexamine (beta-FNA) on the
      binding of [3H]-[D-Ala2, MePhe4, Gly-ol5]enkephalin ([3H]-DAMGO) to homogenates
      of guinea-pig brain and myenteric-plexus longitudinal muscle have been studied.
      2. beta-FNA pretreatment of brain homogenates in Tris-HCl buffer reduced the
      amount of [3H]-DAMGO binding. This was principally due to a reduction in the
      maximal number of binding sites measurable. However, approximately 30% of sites
      labelled by 1 nM [3H]-DAMGO were insensitive to 1 microM beta-FNA. Similar
      findings were obtained when the alkylation was performed in brain homogenates
      prepared in Krebs solution buffered with HEPES. 3. beta-FNA pretreatment of whole
      myenteric-plexus longitudinal muscle strips caused an increase in the IC50 values
      of mu-agonists, but not of kappa-agonists. However, the binding of [3H]-DAMGO to
      homogenates of myenteric-plexus longitudinal muscle was not altered by pre
      incubation with beta-FNA in Tris-HCl buffer. On the other hand when the
      pretreatment was carried out in whole tissue in Krebs solution, or in homogenates
      in the presence of NaCl and Gpp(NH)p, a marked reduction in [3H]-DAMGO binding
      was observed. 4. These results suggest that a low affinity form of the mu-opioid
      receptor is the physiologically relevant site for beta-FNA alkylation in the
      myenteric-plexus and that differences exist between mu-receptor systems in guinea
      pig myenteric plexus and brain.

PMID- 1364845
TI  - Dissociation of a ferric maltol complex and its subsequent metabolism during
      absorption across the small intestine of the rat.
AB  - 1. The fate and disposition of [59Fe]-ferric [3H]-maltol after intravenous
      administration were investigated in anaesthetized rats. Immediate dissociation of
      ferric iron from maltol took place in the circulation even with high doses of
      ferric maltol (containing 1 mg elemental iron). In plasma samples withdrawn
      within 1 min of injection and subjected to gel filtration, 59Fe eluted with the
      high molecular weight proteins whilst the tritium was associated with low
      molecular weight material. 2. The rates of elimination of 59Fe and of tritium
      from the plasma and their ultimate fate were very different. The half life for
      59Fe in the plasma was around 70 min and 59Fe appeared mainly in the bone marrow
      and liver. There was an initial rapid exit of tritium from the plasma with a half
      life of around 12 min. This was followed either by a plateau or by a rise in
      tritium levels, involving entry of maltol metabolites into the circulation. These
      metabolites could be recovered in the urine. 3. Entry of 59Fe and of tritium into
      the blood plasma after intraduodenal administration of [59Fe]-ferric [3H]-maltol
      was also very different. At low doses of ferric maltol (containing 100 micrograms
      elemental iron), the tritium appeared in the plasma in highest amounts within
      seconds and then decreased whilst there was a slow rise in 59Fe levels. At higher
      doses of ferric maltol (containing 7 mg elemental iron), levels of 59Fe in the
      plasma were highest at 5 min and then fell whereas tritium levels rose steadily.
      Mucosal processing of 59Fe prevented further entry of iron at high dose into the
      circulation. 4. Initial rates of uptake of [3H]-maltol into isolatcd intestinal
      fragments were measured over a range of concentrations and revealed that maltol
      alone could diffuse freely into the tissues whereas maltol complexed to iron
      showed saturable uptake kinetics similar to those seen with the iron itself. 5.
      After intestinal uptake, 59Fe and tritium were associated with different
      subcellular fractions, maltol itself being metabolized to the glucuronide
      conjugate within the intestinal mucosa. 6. It is concluded that dissociation of
      metal and ligand takes place before entry into the intestinal mucosa. Iron is
      then taken up on the endogenous carrier and processed in the normal way whilst
      maltol enters by diffusion, its rate of entry being limited by the degree of
      dissociation. It is subsequently metabolized by conjugation and eliminated
      rapidly from the body in the urine.

PMID- 1364846
TI  - Peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) activates capsaicin
      sensitive primary afferent nerves in guinea-pig atria and urinary bladder.
AB  - 1. We have investigated the ability of the N-formyl-methionyl-leucyl
      phenylalanine (FMLP) a synthetic analogue of a chemotactic peptide derived from a
      variety of bacteria, to activate capsaicin-sensitive primary afferents in the
      guinea-pig atria and urinary bladder. 2. In the isolated, electrically-driven
      left atria from reserpine-pretreated guinea-pigs (atropine in the bath), FMLP (3
      nM-1 microM) produced a biphasic positive inotropic response. The late component
      of this response was selectively abolished by in vitro capsaicin pretreatment
      while both the early and late responses were abolished by indomethacin. 3. The
      inotropic response to FMLP in the guinea-pig atria was unaffected by ruthenium
      red. The late but not the early response was strongly inhibited or abolished by
      tetrodotoxin (TTX), omega-conotoxin (CTX) or by the C-terminal fragment (8-37) of
      human alpha-calcitonin gene-related peptide (hCGRP). hCGRP-(8-37) acts as
      competitive antagonist at CGRP receptors. 4. In the guinea-pig isolated bladder,
      FMLP (10 nM-10 microM) produced a concentration-dependent contraction which was
      unchanged by previous in vitro capsaicin, TTX or CTX pretreatment. The response
      to low concentrations of FMLP was suppressed by indomethacin, irrespective of the
      capsaicin pretreatment. 5. FMLP (10 microM) produced a significant increase in
      the outflow of CGRP-like immunoreactivity (CGRP-LI) from superfused guinea-pig
      atria or urinary bladder. CGRP-LI outflow induced by FMLP was blocked by
      indomethacin or in vitro capsaicin pretreatment. 6. These findings indicate that
      FMLP activates the 'efferent' function of capsaicin-sensitive primary afferents
      via prostanoid generation. This action could provide a neurogenic contribution to
      the overall inflammatory response produced by bacteria-derived peptides in
      inflamed tissues. In addition the present data indicate that endogenous
      prostanoids generated during exposure to FMLP produce peptide secretion from
      sensory nerves via a TTX- and CTX-sensitive but ruthenium red-resistant
      mechanism.

PMID- 1364848
TI  - Regional heterogeneity in the contractile and potentiating effects of
      neuropeptide Y in rat isolated coronary arteries: modulatory action of the
      endothelium.
AB  - 1. Neuropeptide Y (NPY) induced a concentration-dependent contraction of isolated
      rings of proximal epicardial (PC) and distal intramural (DC) coronary arteries of
      the rat, with an EC50 of ca. 1 x 10(-7) M. The NPY-induced contraction at 3 x 10(
      7) M was significantly smaller in PC than DC arteries: 34% vs. 55% of the 125 mM
      K(+)-induced response, respectively. 2. NPY (2 x 10(-8) M) increased the
      sensitivity to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) more in PC (4.2
      and 2.8 fold, respectively) than in DC arteries (2.2 and 1.4 fold, respectively).
      The maximal contractile response to NA and 5-HT was increased more in DC (43% and
      29%, respectively) than in PC arteries (20% and 12%, respectively). 3. Removal of
      the endothelium increased the sensitivity and maximal response to NPY as well as
      the spontaneous myogenic tone in PC but not in DC arteries. NPY had no relaxing
      effect on PC and DC arteries submaximally contracted with 10(-6) M prostaglandin
      F2 alpha, suggesting that spontaneous rather than stimulated release of
      endothelium-derived relaxing factor (EDRF) depresses the contractile action of
      NPY in PC arteries. 4. The results indicate a heterogeneity in the contractile
      and potentiating action of NPY in rat coronary arteries depending on size or
      location in the coronary circulation.

PMID- 1364847
TI  - Modification of the rat uterine response to oestrogen and tamoxifen by
      thromboxane antagonists.
AB  - 1. The thromboxane receptor antagonists EP092, AH23848 and BM 13.505 were used to
      investigate the role of thromboxane in the uterotrophic response to oestradiol
      and tamoxifen. 2. The parameters examined were uterine blood flow (measured by
      the microsphere technique), uterine wet and dry weights and the concentrations of
      cytosolic and nuclear oestrogen receptors. 3. Only EP092 potentiated the
      hyperaemic response to oestrogen but all three thromboxane antagonists inhibited
      oestradiol-stimulated uterine growth. This inhibition was accompanied by a
      decrease in nuclear oestrogen receptor concentration. 4. The uterotrophic
      response to tamoxifen was unaffected by the thromboxane antagonists. 5. The
      mechanism by which the thromboxane antagonists may be exerting their growth
      inhibitory effect is discussed, although, whether this effect can be attributed
      to blockade of thromboxane receptors or to some other mechanism is not clear from
      this study.

PMID- 1364849
TI  - The role of nitric oxide as an endogenous regulator of platelet and neutrophil
      activation within the pulmonary circulation of the rabbit.
AB  - 1. Intravenous (i.v.) administration of adenosine diphosphate (ADP), platelet
      activating factor (PAF) and thrombin induced a dose-related accumulation of
      111indium-labelled platelets within the thoracic region of anaesthetized rabbits.
      2. I.v. administration of the inhibitor of NO biosynthesis, L-NG-nitro arginine
      methyl ester (L-NAME; 10 mg kg-1) significantly potentiated the peak platelet
      accumulation induced by ADP, PAF and thrombin. Additionally L-NAME prolonged the
      disaggregation of platelets in comparison to D-NAME (10 mg kg-1). Such changes
      were reversible by the administration of L-arginine (900 mg kg-1). 3. I.v.
      administration of PAF induced a small accumulation of 111indium-labelled
      neutrophils within the pulmonary circulation which could be greatly potentiated
      by pretreatment of the animals with L-NAME. In contrast, thrombin administration
      did not cause significant accumulation of 11indium-labelled erythrocytes in the
      pulmonary circulation of anaesthetized rabbits. 4. Intracarotid (i.c.)
      administration of thrombin induced a marked accumulation of radiolabelled
      platelets within the cranial vasculature which was not potentiated by the prior
      administration of L-NAME (at either 10 mg kg-1 or 100 mg kg-1). 5. These results
      suggest that endogenous NO may regulate platelet and polymorphonuclear leukocyte
      activation within the pulmonary but not the cerebral circulation of rabbits.

PMID- 1364850
TI  - 4-Aminopyridine-induced increase in basal and stimulation-evoked [3H]-NA release
      in slices from rat hippocampus: Ca2+ sensitivity and presynaptic control.
AB  - 1. We have examined the mechanisms by which the K(+)-channel blocker 4
      aminopyridine (4-AP) can dose-dependently increase both basal [3H]-noradrenaline
      ([3H]-NA) release and the [3H]-NA release evoked by electrical stimulation, but
      not the release of [3H]-acetylcholine ([3H]-ACh), from slices of rat hippocampus.
      2. Both the electrically evoked and the 4-AP-induced release were blocked by
      tetrodotoxin (TTX) (3 microM). The Ca(2+)-dependence of the 4-AP-induced release
      (EC50 0.15 mM) was, however, different from that of the electrically evoked [3H]
      NA release (EC50 0.76 mM). 3. The 4-AP-induced release could be inhibited by
      CdCl2(10 microM) and omega-conotoxin (30 nM), but not by nifedipine (1 microM).
      4. Transmitter release evoked by 100 microM 4-AP could be blocked by the alpha 2
      adrenoceptor agonist, UK 14,304 (0.1 microM) and by the A1-receptor agonist R-N6
      phenylisopropyl adenosine (R-PIA, 1 microM) and increased by the alpha 2
      adrenoceptor antagonist, yohimbine (1 microM), both in 0.25 and 1.3 mM Ca(2+)
      containing medium. By contrast, the effect of alpha 2-adrenoceptor agonist and
      antagonists on transmitter release evoked by electrical stimulation was markedly
      reduced in the presence of 4-AP (100 microM). 5. The results suggest that 4-AP
      can depolarize some nerve endings in the central nervous system, leading to
      transmitter release that is dependent on nerve impulses and Ca2+. Furthermore,
      the fact that alpha 2-receptors and adenosine A1 receptor agonists can influence
      the release of NA evoked by 4-AP suggests that these drugs may have actions that
      are independent of blockade of aminopyridine-sensitive K(+)-channels.

PMID- 1364851
TI  - Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies.
AB  - 1. Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]bradykinin) is a new bradykinin (BK)
      antagonist. It was tested in several in vitro assays and compared with D-Arg
      [Hyp2,Thi5,8,D-Phe7]BK. 2. In receptor binding studies in guinea-pig ileum
      preparations, Hoe 140 showed an IC50 of 1.07 x 10(-9) mol l-1 and a KI value of
      7.98 x 10(-10) mol l-1. 3. In isolated organ preparations Hoe 140 and D-Arg
      [Hyp2,Thi5,8, D-Phe7]BK inhibited bradykinin-induced contractions concentration
      dependently, with IC50-values in the guinea-pig ileum preparation of 1.1 x 10(-8)
      mol l-1 and 3 x 10(-5) mol l-1, respectively. pA2 values in this tissue were 8.42
      and 6.18, respectively. In the rat uterus preparation the IC50 value was 4.9 x
      10(-9) mol l-1 for Hoe 140. D-Arg-[Hyp2, Thi5,8, D-Phe7]BK showed an IC50 of 4.0
      x 10(-6) mol l-1. The IC50 values in the guinea-pig isolated pulmonary artery
      were 5.4 x 10(-9) mol l-1 and 6.4 x 10(-6) mol l-1, respectively. In the rabbit
      aorta no inhibitory effects on Des-Arg9-BK induced contractions were observed. 4.
      In cultured bovine endothelial cells, Hoe 140 antagonized (IC50 = 10(-8) mol l-1)
      bradykinin-induced endothelium-derived relaxing factor (EDRF) release and the
      bradykinin-induced increase in cytosolic free calcium (IC50 = 10(-9) mol l-1). 5.
      Hoe 140 (10 -7mol I1) totally suppressed the bradykinin-induced (10 8 to 10- mol
      I') prostacyclin (PGI2) release from cultured endothelial cells of bovine aorta.
      D-Arg-[Hyp2, Thi5'8, D-Phe7]BK (10- 7 mol I1- ) showed a weaker antagonism. 6.
      Taken together these results show that Hoe 140 is a highly potent bradykinin
      antagonist. It was two to three orders of magnitude more potent than D-Arg-[Hyp2,
      Thi5 8, D-Phe7]BK.

PMID- 1364852
TI  - Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies.
AB  - 1. The potency, duration of action and tolerability of Hoe 140, a novel and
      highly potent bradykinin (BK) antagonist in vitro, has been tested in different
      in vivo models and compared with the well-known BK antagonist D-Arg-[Hyp2,
      Thi5,8, D-Phe7]BK. 2. Hoe 140 is highly potent and long acting in inhibiting BK
      induced hypotensive responses in the rat. Four hours after s.c. administration of
      20 nmol kg-1, inhibition still amounted to 60% whereas the effect of 200 nmol kg
      1 of D-Arg-[Hyp2, Thi5,8, D-Phe7]BK was not significant. 3. BK-induced
      bronchoconstriction in guinea-pigs was strongly inhibited by Hoe 140. The
      magnitude and duration of inhibition confirmed the findings obtained in the blood
      pressure experiments in the rat. 4. Carrageenin-induced inflammatory oedema of
      the rat paw was considerably inhibited at i.v. doses between 0.1 and 1 mg kg-1.
      5. In conscious dogs, intravenous doses of 0.01 and 0.1 mg kg-1 of Hoe 140 and D
      Arg-[Hyp2, Thi5,8, D-Phe7]BK were well tolerated. At doses of 1 mg kg-1 adverse
      effects occurred that were attributed to the residual BK agonistic activity of
      both compounds. 6. Hoe 140 has been shown to be a highly potent and long acting
      BK antagonist in vivo in different animal species and models. This makes it
      appropriate to investigate further the physiological and pathophysiological role
      of BK.

PMID- 1364854
TI  - Proceedings of the SEAMEO TROPMED technical meeting on: advanced knowledge on
      malaria in Southeast Asia. Bangkok, Thailand, November 19-21, 1991.

PMID- 1364855
TI  - Response to new drug regimens in man of multi-drug resistant falciparum malaria.

PMID- 1364853
TI  - Deamination of newly-formed dopamine in rat renal tissues.
AB  - 1. The present study has examined the formation of dopamine and 3,4
      dihydroxyphenylacetic acid (DOPAC) in slices of the rat renal cortex and the
      renal medulla loaded with exogenous L-beta-3,4-dihydroxyphenylalanine (L-DOPA).
      The effects of pargyline and of two selective inhibitors of monoamine oxidase
      (MAO) types A and B, respectively Ro 41-1049 and Ro 19-6327, on the deamination
      of newly-synthesized dopamine in kidney slices incubated with exogenous L-DOPA
      were also tested. The assay of L-DOPA, dopamine, noradrenaline and DOPAC was
      performed by means of h.p.l.c. with electrochemical detection. 2. Incubation of
      renal slices with exogenous L-DOPA resulted in a concentration-dependent
      accumulation of dopamine and DOPAC; the tissue levels of newly-formed dopamine
      and DOPAC in slices of the renal medulla were 6-8% of those in cortical slices.
      3. Pargyline (0.1 mM) produced a marked decrease (84% reduction) in the formation
      of DOPAC in kidney slices loaded with 1.0 mM L-DOPA; this effect was accompanied
      by a 17% increase in the accumulation of dopamine. Similar effects were obtained
      at higher concentrations of pargyline (0.5 and 1.0 mM). At 5.0 and 10.0 mM
      pargyline, a marked decrease (46 and 76% reduction) in the accumulation of newly
      formed dopamine was observed. 4. The accumulation of dopamine and DOPAC was found
      to be time-dependent in experiments in which tissues were incubated with 5 and 10
      microM L-DOPA for 5, 10, 20 and 30 min. Pargyline (0.1 mM) produced an increase
      in the accumulation of dopamine at all incubation periods and decreased the
      formation of DOPAC. 6. It is concluded that deamination of newly-formed dopamine
      in kidney slices loaded with L-DOPA constitutes an important mechanism of amine
      inactivation. The results presented also suggest that most of the MAO, located
      inside the compartment where the synthesis of dopamine occurs, is of the A type.

PMID- 1364856
TI  - The effect of artemether plus mefloquine on Myanmar patients with complicated
      falciparum malaria.
AB  - The effect of artemether plus mefloquine versus quinine on 35 patients with
      complicated falciparum malaria including 5 patients with cerebral malaria were
      studied. All patients treated with the artemether-mefloquine combination survived
      and all were free from toxic effects of the drugs. Three patients on quinine
      therapy died. The mortality rate was 8.5%. The mean parasite clearance time of
      patients treated with artemether plus mefloquine was significantly shorter than
      those treated with quinine but there was no significant difference in the mean
      fever clearance of the two groups of patients. There was no recrudescence with
      artemether and mefloquine; the recrudescence rate was 5.5% with quinine. The
      study showed that the artemether-mefloquine combination is superior to quinine
      for the treatment of patients with complicated falciparum malaria, including
      cerebral malaria.

PMID- 1364857
TI  - The biological and epidemiological basis of drug resistance in malaria parasites.
AB  - Natural populations of Plasmodium falciparum without previous drug exposure are
      mixtures of individual parasites with different levels of response to a specific
      medicament. Exposure to sublethal drug concentrations will eliminate the highly
      and moderately sensitive individuals. The less sensitive part of the parasite
      population is being selected and given the opportunity of propagating. Underdosed
      mass drug administration and subcurative medication have this direct effect. An
      indirect effect with the same result is observed with drugs having a long half
      life, where new infections invade the blood while subtherapeutic residual drug
      concentrations are still present. This militates against the use of drugs with
      long half-life in areas with intensive malaria transmission, and for a rational
      therapeutic use of alternative antimalarials based on reliable microscopic
      diagnosis, adequate dose regimens, post-treatment follow-up, further alternative
      treatment of recrudescences with the objective of radical cure.

PMID- 1364858
TI  - Overview: epidemiology of malaria and its control in countries of the WHO South
      East Asia region.
AB  - The malaria situation in the WHO South-East Asia Region is reviewed in terms of
      its epidemiological diversity, problems encountered and implications for control.
      Varying host-parasite-vector interrelationships are shown to be influenced
      significantly by prevailing environmental conditions (eg topographic, climatic)
      as well as behavioral and socio-economic determinants. Drug-resistant falciparum
      malaria and vector resistance to insecticides are the main biological deterrents
      to the success of control programs. Thus, the potential for malaria transmission
      remains high in many places. The malaria control strategy includes Primary Health
      Care and integration with basic health services. However, operational research is
      needed in many of the countries in the Region.

PMID- 1364859
TI  - Dynamics of multi-drug resistance in Plasmodium falciparum in Thailand.
AB  - Since the initial report of resistance of Plasmodium falciparum to chloroquine in
      1960 in the Thai-Cambodian border resistance to alternative drugs occurred early
      after their introduction. This development is considered to be the result of
      population migration and excessive drug pressure along with the presence of a
      multi-resistance gene within the parasite population. Multi-resistant strains as
      such have been disseminated throughout the country by returning migrant
      populations.

PMID- 1364860
TI  - Current measures of containment of multi-drug resistant falciparum malaria in
      Thailand.
AB  - Resistance of P. falciparum to mefloquine emerged along the Thai-Cambodian border
      following the falciparum malaria outbreak in Bo Rai areas in late 1988. Efforts
      have been made since then to prevent or delay the spread of multi-drug resistant
      strains by restricting the use of mefloquine, limiting the distribution of the
      drug for presumptive treatment and chemoprophylaxis, encouraging personal
      protection, strengthening the case follow-up system, increasing physician
      awareness, and mass treatment with primaquine of gem miners crossing the borders.

PMID- 1364861
TI  - In vitro sensitivity of Plasmodium falciparum to chloroquine and other
      antimalarials in east Timor and east Kalimantan, Indonesia.
AB  - In Indonesia resistance of Plasmodium falciparum to chloroquine has spread to all
      provinces except Yogyakarta since the first report in 1974. The proportion of
      resistant cases is relatively low except in Irian Jaya and East Timor. The
      results of in vitro tests performed in East Timor showed 81.0% resistance to
      chloroquine, 87.5% to amodiaquine, 20.0% to sulfadoxine-pyrimethamine (S-P), 4.8%
      to mefloquine, and 100% sensitivity to quinine. The percentage of failures was
      between 11.1% and 71.4% and highest with the S-P combination. Multidrug
      resistance was observed in 9 cases (or 11.1%). The results of in vitro tests in
      East Kalimantan were: 62.8% resistance to chloroquine, 100% to amodiaquine, 85.7%
      to S-P combination, 3.2% to quinine, and 2.5% to mefloquine. Failures rates
      ranged between 21.2% and 37.1% the highest being with mefloquine. Multidrug
      resistance was more prominent and observed in 59 cases (84.3%) of which one case
      was resistant to 5 antimalarials, while 4 cases (5.7%) were resistant to
      chloroquine only, compared to 72 cases (88.9%) in East Timor.

PMID- 1364862
TI  - Drug resistance in the Philippines.

PMID- 1364863
TI  - Overview: pathophysiology and management of cerebral malaria.
AB  - Cerebral malaria is still a major cause of death in patients suffering from
      malaria. Much of the research work in the past two decades has been done to
      clarify the pathophysiology of cerebral malaria which hopes to improve the
      management of the disease and concomitantly reduce mortality. However, the
      pathogenesis of cerebral malaria is still not clear. The pathophysiology of coma
      is believed to be brain anoxia from ischemia due to sequestration of erythrocytes
      containing mature parasites in cerebral capillaries and venules. Three possible
      mechanisms of sequestration (cytoadherence, rosette formation and decreased
      deformability of the infected erythrocytes) are postulated. The management of
      cerebral malaria includes early diagnosis and early treatment with potent
      antimalarial drugs, early detection and treatment of complications, correction of
      fluid and electrolyte imbalance and proper nursing care. In spite of these
      efforts, a high mortality rate (ranging 10-40%) is still encountered.

PMID- 1364864
TI  - Malaria in Cambodia.
AB  - There are around half a million cases of malaria with 5-10,000 deaths per year in
      Cambodia. Incidence rates vary in different parts of the country. Malaria control
      is hampered by multiple drug resistance of Plasmodium falciparum, inaccessibility
      to the major vector, poor security in most malarious areas, and lack of
      resources. The control strategy emphasises improvement of clinical management and
      provision of prompt and accurate diagnosis in order to reduce morbidity and to
      prevent mortality. In addition health information and drug distribution systems
      are being improved. The use of pyrethroid-treated mosquito nets and health
      education are being promoted. Particular attention is given to returning refugees
      as they settle into the country.

PMID- 1364865
TI  - Malaria control program in Indonesia.
AB  - The malaria situation in Indonesia is reviewed in the major island group of Java
      Bali and the remainder of the archipelago called the Outer Islands. Based on
      their varying epidemiological patterns the areas for control have been stratified
      and efforts are directed towards the rational use of antimalarial drugs and the
      institution of integrated vector control ie chemical control in conjunction with
      biological control and environmental management. The targets of malaria control
      vary as well between island groups. Administrative, technical and operational
      constraints are identified. Drug-resistant malaria, forest-related malaria, lack
      of personnel, supervision and coordination, inadequate resources, and community
      participation are among the main issues confronting the national malaria control
      program. Research and training needs are emphasized in the recommendations.

PMID- 1364866
TI  - The malaria situation and antimalaria program in Laos.
AB  - Malaria is endemic in all 17 provinces of Laos. Transmission is perennial with a
      "seasonal peak" coinciding with the rainy season. The vectors Anopheles minimus
      and An. balabacensis (=dirus) remain susceptible to DDT. Chloroquine-resistance
      of Plasmodium falciparum is at the RI-RII level. Multidrug resistance is not yet
      a problem. Major constraints of the antimalaria program involve logistics and
      operational problems solutions to which are specifically addressed in the
      recommendations.

PMID- 1364867
TI  - Current status of malaria in Malaysia.
AB  - The Malaria Eradication Program was started in 1967 in Peninsular Malaysia. Since
      then and up to 1980, there was a reduction in the number of reported malaria
      cases from 160,385 in 1966 to 9,110 cases for Peninsular Malaysia. Although the
      concept of eradication has changed to one of control in the 1980, the anti
      malaria activities have remained the same. However, additional supplementary
      activities such as the use of impregnated bednets, and the Primary Health Care
      approach, have been introduced in malarious and malaria-prone areas. Focal
      spraying activity is instituted in localities with outbreaks in both malaria
      prone and non-malarious areas. Passive case detection has been maintained in all
      operational areas. In 1990, 50,500 cases of malaria were reported of which 69.7%
      (35,190) were from Sabah, 27.8% (14,066) from Peninsular Malaysia and 2.5%
      (1,244) from Sarawak. Until June 1991 a total of 18,306 cases were reported for
      the country. Plasmodium falciparum continues to be the predominant species,
      contributing to 69.6% of the parasites involved. The case fatality rate for 1990
      was 0.09%. There were 43 deaths all of which were attributed to cerebral malaria.
      The problems faced in the prevention and control of malaria include problems
      associated with the opening of land for agriculture, mobility of the aborigines
      of Peninsular Malaysia (Orang Asli) and inaccessibility of malaria problem areas.
      There is need to ensure prompt investigation and complete treatment of cases
      especially in malarious areas. The promotion of community participation in
      control activities should be intensified. Primary Health Care should be continued
      and intensified in the malarious areas.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364868
TI  - Malaria control in Myanmar.

PMID- 1364869
TI  - Current status of malaria and control activities in the Philippines.
AB  - The paper attempts to present the current malaria situation in the Philippines
      which includes its distribution, morbidity and mortality rates, parasitology, the
      appearance of drug-resistant parasites, and entomological aspects. Under the
      current malaria control program, the objective is to reduce the incidence of
      malaria to one per one thousand population by year 2000 and to prevent its
      reintroduction to malaria-freed areas. Following the tactical variants of malaria
      control advocated by WHO, the program successfully reduced the incidence from
      14.5/1,000 population in 1987 to 7.3/1,000 in 1990 but leveled off in 1991.
      Malaria is still among the 10 leading causes of morbidity. Problems encountered
      and research priorities are included in the report.

PMID- 1364870
TI  - Malaria control program in Sri Lanka.

PMID- 1364871
TI  - Overview: immunology of malaria and progress in malaria vaccine development.

PMID- 1364872
TI  - Vaccine strategies for malaria: applicability in areas of seasonal or epidemic
      malaria.
AB  - The likely effects of different vaccine strategies was tested using computer
      simulation of malaria transmission. In areas of seasonal or epidemic malaria,
      vaccines directed against all stages (pre-erythrocytic, erythrocytic and sexual)
      gave similar reductions in disease transmission. These models indicate that such
      vaccines may be much more effective that commonly predicted. The major effect
      will be to slow the spread of, rather than totally prevent malaria. As such, the
      use of such vaccines will be heavily dependent on integrated control programs
      involving other forms of control.

PMID- 1364873
TI  - Overview: clinical pharmacology of antimalarials.
AB  - The effectiveness of antimalarials depends on its pharmacodynamics ie inhibitory
      effect on the parasites and unwanted effects on the host. It also depends on the
      pharmacokinetics of the drugs. The ideal antimalarials are drugs that show
      curative activity in the absence of toxicity to the host. Recommendation for
      antimalarial dosage regimens should be based on pharmacokinetic and
      pharmacodynamic studies in appropriate populations ie ethnic groups, adults
      children, and in pregnancy. Chloroquine remains the drug of choice for treating
      malaria caused by Plasmodium species other than P. falciparum. Even in the
      presence of chloroquine resistance the drug may still be quite useful, especially
      in areas with high communal immunity. In general sulfadoxine/pyrimethamine (S/P)
      should be used as an alternative antimalarial when chloroquine fails. The
      decision to change to S/P from chloroquine depends on many factors. Quinine still
      remains the drug of choice for severe chloroquine-resistant falciparum malaria.
      Resistance to mefloquine has appeared the exact mechanism being unknown. In
      general, before the use of any combination of antimalarial drugs the superiority
      (efficacy and side-effects) over each of the individual drugs should be clearly
      demonstrated. The combination of mefloquine with sulfadoxine/pyrimethamine was
      made on the grounds that the combination would delay the resistance to
      mefloquine. Desferrioxamine will hardly be an agent to be used on its own for
      treating malaria due to the high recrudescent rate. However, a recent report
      indicated that its association with antimalarial drugs in the management of
      severe and complicated falciparum malaria shortens fever and parasite clearance
      time and resolves complications faster than the standard antimalarial drug alone.
      Clinical trials with halofantrine has been done in several countries in the
      region from 1988 to the present with diverse results. Further studies on a larger
      scale should be carried out to ascertain whether these are due to variation in
      drug absorption or drug resistance. An improved formulation of halofantrine must
      be developed to ensure adequate absorption and bioavailability. The artermisinin
      group of antimalarials is known to be highly effective and independent, in its
      mode of action, from standard malaria drugs but associated with high recrudescent
      rate. Phase II studies are needed for determining/optimizing therapeutic dose
      regimens and to ensure safer and more effective use of these compounds.

PMID- 1364874
TI  - [The missing inflammatory syndrome].
AB  - An inflammatory disease is sometimes suspected despite a normal erythrocyte
      sedimentation rate (ESR). When this dissociation is present, the reasons for the
      lack of ESR elevation, which concern the red cells, the plasma and the laboratory
      techniques, must be excluded, the reality of the inflammatory syndrome being then
      confirmed by assay of the inflammatory proteins. However, an inflammatory
      syndrome is missing in 5 to 10 percent of inflammatory diseases, more frequently
      in cases of polymyositis or scleroderma, less frequently in those of giant cell
      arteritis. Little information can be found in the literature, concerning the
      missing inflammatory syndrome. Does it confer peculiar semeiological or
      prognostic features? Is the dissociation related to the patient, as would appear
      in some special cases, or to the disease, as suggested by the small rise of the C
      reactive protein in acute episodes of lupus erythematosus? The absence of
      inflammatory syndrome is a source of diagnostic problems when the symptoms are
      atypical or when there are no specific signs of the suspected disease.
      Differential diagnoses, especially non-inflammatory diseases, must then be
      carefully discussed. Improving our knowledge of the missing inflammatory syndrome
      would require the creation of this key-word.

PMID- 1364875
TI  - [Remarks on the assessment of anesthesia relative complexity index without taking
      notice of the code of the surgical procedure].

PMID- 1364876
TI  - [Methodology of chronopharmacological studies].

PMID- 1364877
TI  - [Validity of positive anti-Borrelia antibodies in patients with
      neuroborreliosis].

PMID- 1364878
TI  - [Infective iliopsoas bursitis].

PMID- 1364879
TI  - [Smooth muscle hamartoma and congenital hypertrichosis].

PMID- 1364880
TI  - Update on AIDS--worldwide.

PMID- 1364881
TI  - A case of HIV infection possibly transmitted in an occupational setting--Ontario.

PMID- 1364882
TI  - National surveillance of occupational exposure to the human immunodeficiency
      virus (HIV).

PMID- 1364883
TI  - HIV-negative individuals with AIDS.

PMID- 1364884
TI  - Progression of prevalence of HIV-1 infection among injection drug users in
      Montreal, Quebec.

PMID- 1364886
TI  - [Electroneuromyography in nerve injury--principles, possibilities and
      restrictions].

PMID- 1364885
TI  - [Diabetic individual as a surgical patient].

PMID- 1364887
TI  - [Antiestrogens in gynecology].

PMID- 1364888
TI  - [Should Helicobacter infection be treated?].

PMID- 1364889
TI  - [Is contraceptive injection for men possible after all?].

PMID- 1364890
TI  - [Hypertension and the prevention of cerebral vascular diseases].

PMID- 1364891
TI  - [Changed ulcer surgery in the era of H2-blockers].

PMID- 1364892
TI  - [Progressive neurological symptoms and fatal cardiomyopathy in a middle-aged
      man].

PMID- 1364893
TI  - [Treatment and follow-up of thyroid cancer].

PMID- 1364894
TI  - [Development of orthopedics during the past 50 years].

PMID- 1364895
TI  - [Orthopedics in health care].

PMID- 1364896
TI  - [Endoprostheses in Finland].

PMID- 1364897
TI  - [Growth defects of extremities].

PMID- 1364898
TI  - [Operative treatment of growth plate injury].

PMID- 1364899
TI  - [Childhood back problems].

PMID- 1364900
TI  - [Congenital dislocation of the hip].

PMID- 1364901
TI  - [New surgical methods in the treatment of back diseases].

PMID- 1364902
TI  - [The hip of the working-aged individual: principles in surgical management].

PMID- 1364903
TI  - [Aseptic necrosis of the femoral head].

PMID- 1364904
TI  - [Current techniques in revision total hip arthroplasty].

PMID- 1364905
TI  - [Hip arthroplasty infections].

PMID- 1364906
TI  - [Diagnosis and treatment of anterior cruciate ligament tears].

PMID- 1364907
TI  - [Timing of surgical intervention in rheumatoid arthritis].

PMID- 1364908
TI  - [Unstable shoulder joint].

PMID- 1364909
TI  - [Treatment of flexor tendon injuries].

PMID- 1364910
TI  - [Orthopedic infections].

PMID- 1364911
TI  - [Orthopedics and rehabilitation].

PMID- 1364912
TI  - [The pathogenesis of polyneuropathies].

PMID- 1364913
TI  - [Hormone treatment of breast cancer].

PMID- 1364914
TI  - [Magnetic resonance imaging of upper abdomen].

PMID- 1364915
TI  - [Laboratory findings in purulent arthritis in adults].

PMID- 1364916
TI  - [Cytomegalovirus infections in immunosuppressed patients].

PMID- 1364917
TI  - [Gene localization will explain the basic causes of neuronal ceroid
      lipofuscinoses].

PMID- 1364918
TI  - [New medications for depression].

PMID- 1364919
TI  - [The progression of polycythemia vera to chronic myeloid leukemia].

PMID- 1364920
TI  - [Sparing breast cancer surgery].

PMID- 1364921
TI  - [Recurrent abdominal symptoms in a woman and laboratory values indicating
      infection].

PMID- 1364922
TI  - [Is raw carrot the best source of beta carotene?].

PMID- 1364923
TI  - [The effects and possibilities of clinical use of antioxidants].

PMID- 1364924
TI  - [Seasonal affective disorder].

PMID- 1364925
TI  - [Carcinoma in situ in seminiferous epithelium].

PMID- 1364926
TI  - [Did the Chernobyl accident cause anomalies in fetuses?].

PMID- 1364927
TI  - [What is new in the treatment of osteoporosis?].

PMID- 1364928
TI  - [Association between cancer and exposure to chlorophenols in a county located in
      southern Finland].

PMID- 1364929
TI  - [Torsion of intra-abdominal seminoma of testis].

PMID- 1364930
TI  - [Hypoglycemia as a complication of insulin therapy].

PMID- 1364931
TI  - [Course of events in death certificate].

PMID- 1364932
TI  - [The diagnosis and treatment of vertigo].

PMID- 1364933
TI  - Naproxen: its current place in therapeutics.

PMID- 1364934
TI  - The outcome of arthritis: measures of function, X-rays damage, pain and patients'
      satisfaction.
AB  - The outcome of arthritis has several dimensions. These include mortality,
      morbidity, radiological measures of joint destruction, pain, and patients'
      satisfaction with therapy. Functional disability measured by health status
      questionnaires, is directly associated with long-term outcome and mortality. Long
      term clinical trials should incorporate functional indices as outcome measures.
      Studies measuring the outcome of arthritis should define clear end-points
      involving the determination of functional classes and this will allow
      standardised and sensitive end points. An example would be the time taken to
      reach a given functional class or increase from baseline by one functional class.
      Patients' satisfaction with treatment is a different dimension of response. There
      are considerable advantages in using an index of patients' satisfaction when
      determining the therapeutic efficacy in short term clinical trials. It gives a
      different indication of the response to treatment than conventional clinical and
      laboratory measures of disease activity. Alleviating pain and preservation of
      function remain the major therapeutic goals, and both reflect the outcome of
      arthritis. Outcome measures have shifted from laboratory markers and radiographic
      techniques to measures of health status, pain, and patients' satisfaction. These
      should become a routine part of patient assessment.

PMID- 1364935
TI  - Enteric coated naproxen; a double blind trial comparing the tolerance of enteric
      coated and standard formulations.
AB  - Enteric coated naproxen (Nycopren) was compared with standard naproxen in a
      double blind comparative trial of 348 patients with either rheumatoid or
      osteoarthritis. There were slightly fewer gastric side effects and slightly fewer
      withdrawals because of side effects in the enteric coated naproxen group but the
      differences did not reach statistical significance. There was no significant
      difference in the efficacy of the two formulations. A satisfaction index was used
      to assess the therapeutic ratio with visual analogue scales assigned to both
      efficacy and side effects. The scale performed as intended and is worthy of
      further exploration.

PMID- 1364936
TI  - Enteric-coated and plain naproxen tablets in osteoarthritis; tolerability and
      efficacy.
AB  - The aim of this 8 week study, was to compare the tolerability and efficacy of
      enteric-coated (ECT) and plain naproxen tablets (PT). Ninety eight patients (mean
      age 66 years) with osteoarthritis were included in a randomized, multi-centre,
      double-blind, cross-over study. Response variables were monitored at 2 week
      intervals for the duration of the study. Sixteen patients withdrew from the
      study, eight because of gastrointestinal (GI) adverse events (ECT 5, PT3). There
      was no significant difference in patients preference. Eighteen patients reported
      GI adverse events only on PT compared to 9 on ECT (n.s.). In the first treatment
      period the severity of adverse events was significantly less on ECT (P = 0.015).
      Both enteric-coated and plain naproxen tablets were effective and well tolerated.
      In conclusion, the study did not show any clinical significant difference in
      tolerability or efficacy between the formulations in osteoarthritis of the knee
      and/or the hip, although some of the variables did show statistical significant
      difference or tendency in favour of the enteric coated tablets.

PMID- 1364937
TI  - Morning stiffness and nightime pain in ankylosing spondylitis. A comparison
      between enteric-coated and plain naproxen tablets.
AB  - Thirty-nine patients with ankylosing spondylitis participated in a randomized,
      double-blind, double-dummy, multi-cross-over study with enteric-coated (ECT) and
      plain (PT) naproxen tablets. The duration of the study was 24 days with 6
      treatment periods of 4 days. The majority of the patients were taking 750 mg
      naproxen daily. The mean plasma concentration of naproxen in the morning was 36%
      higher with ECT (p < 0.001). No significant differences regarding duration of
      morning stiffness and night time pain were found in this patient category. The
      mean duration of morning stiffness was 116 minutes (ECT) and 125 minutes (PT). We
      were not able to show correlation between plasma concentration of naproxen and
      duration of morning stiffness.

PMID- 1364938
TI  - The formulation of non-steroidal anti-inflammatory drugs: enteric coated
      naproxen.

PMID- 1364939
TI  - Naproxen-associated gastroduodenal toxicity: enteric coated granules versus plain
      tablets.
AB  - Two naproxen formulations were compared with regard to gastroduodenal endoscopic
      findings. Using a dose of 500 mg bid for one week, plain tablets were compared to
      enteric coated granules in a gelatine capsule in a randomized, cross over, double
      blind, double dummy study in 16 healthy, male volunteers. Endoscopic evaluation
      revealed no difference between the two formulations. Since previous studies with
      enteric coated naproxen tablets indicated a favourable side effect profile
      compared to plain tablets, the present data indicates that enteric coated
      formulations are not all alike, and should be studied individually.

PMID- 1364940
TI  - Enteric coated naproxen tablets.
AB  - It is postulated that the gastroduodenal mucosal side effects of naproxen are
      partly based on topical toxicity. With enteric coated aspirin tablets as a model
      product, enteric coated naproxen formulations have been developed. The extent of
      absorption is the same for enteric coated and plain tablets. The onset of
      absorption is delayed as a result of retention of larger particles in the stomach
      and more so when taken along with food. The gastric emptying of enteric coated
      naproxen granules is less influenced by food intake, but so far without any
      verified reduction of gastroscopic findings. The gastro-intestinal transmit has
      been studied by use of gamma scintigraphy.

PMID- 1364941
TI  - NSAID-associated gastrointestinal damage: methodological considerations and a
      review of the experience with enteric coated naproxen.
AB  - Various methods are available for investigating gastrointestinal adverse effects
      of NSAIDs. Upper endoscopy is regarded a gold standard for controlled studies,
      but the grading and categorization of the visual impression of mucosal changes is
      complicated. Faecal blood loss represents another aspect of the toxicity, but
      quantitative measurements require the cumbersome procedure of 51Cr-labelling of
      red blood cells. For monitoring distal gut effects, permeability tests can be
      applied, and combination of tracer substances may further enhance the method.
      Measurements of electrical potential differences over the gastric mucosa are also
      available to monitor functional aspects of the gastric mucosal integrity.
      Controlled endoscopic trials have indicated an advantage of enteric coated
      naproxen tablets over plain tablets. Distal transfer of the toxicity by small
      bowel release of the active substance, has not been confirmed by permeability
      tests.

PMID- 1364942
TI  - Retraction of Ross and LoLordo findings concerning blocking in serial feature
      positive discriminations.
AB  - Findings concerning the effectiveness of stimuli from various conditioning
      procedures in blocking conditioned excitation and occasion-setting functions of
      an added stimulus in a serial feature-postive discrimination training procedure
      (LoLordo & Ross, 1987; Ross & LoLordo, 1986, 1987) are retracted. Videotapes on
      which the published data were based were rescored by 2-5 people, most of whom
      were uninformed about group memberships of the subjects. In no case did the
      rescoring confirm any of the orginal findings of blocking. Possible factors
      contributing to the discrepancies are discussed. The experiments should be
      repeated with feature stimuli that are less similar to each other and with
      several scorers, at least one of whom is unaware of the group assignment of the
      subjects.

PMID- 1364943
TI  - Expert computer program for the management of laser surgery.
AB  - Since 1960 when the first laser was produced, different types of lasers were
      developed and over one hundred of them are actually used in medicine. These facts
      makes very difficult for a surgeon to optimally utilize different types of laser
      in varying surgical circumstances, unless a laser expert is actually
      participating in the procedure. As this presence is impractical, if not
      impossible in every case, we are offering a computer program which presents
      information in a flexible and friendly way; it is self perfecting and greatly
      expandable.

PMID- 1364944
TI  - [Anthropometric study of students of Palo Blanco, Department of Tinogasta,
      Province of Catamarca, Argentina].
AB  - An anthropometric cross-sectional research was carried out in 211 students from
      Palo Blanco, in Tinogasta, Catamarca province. They were 110 boys and 101 girls
      aged 6-12 years, and they attended classes at the local school. Palo Blanco is a
      rural place, in a "very unfavorable" area, located on the west of Catamarca
      province, at 1.700 meters above sea level. Its climate is continental and half
      deserted with a large diurnal thermometrical range. Measurements of body weight
      and standing height were obtained; then their averages and percentiles were
      compared with measurements of two samples obtained from urban areas. One of them
      was taken from students attending classes in Tinogasta (a city that belongs to
      the district having the sa-name), and the other from Catamarca city (the Capital
      of the province). Its aim was to determine the existence of some differences in
      the variables that were investigated, and that could de due to the rural
      situation of Palo Blanco's students. The anthropometrical variables in Palo
      Blanco's students resulted in values similar to those obtained in Tinogasta city,
      while both of them showed a significant difference, not only in body weight but
      also in standing height, in comparison to the students from the head city of
      Catamarca, especially in males. It may be concluded that conditions that differ
      from those derived of the rural situation, have incidence upon the behavior of
      these anthropometrical variables.

PMID- 1364945
TI  - Spontaneous formation of rosettes by autologous human monocyte-macrophages and
      lymphocytes in cell cultures.

PMID- 1364946
TI  - [Pancreatic ascites and pleural effusion].
AB  - Pancreatic ascites consists in the presence of pancreatic juice into the
      peritoneal cavity, coming from pseudocysts or pancreatic ducts breaches, that
      produce the accumulation of an exudate rich in proteins and amylase; these
      findings certify the diagnosis. We report a case of pancreatic ascites with
      pleural effusion: alcoholic patient, without previous episodes of acute
      pancreatitis, with ascites, weight loss, abdominal pain, right pleural effusion,
      insidious onset, blood level of amylase: more than 1024 UD; CT: ascites, right
      pleural effusion, pseudocyst in the head (24 mm) and in the tail (77 mm) of the
      pancreas. TREATMENT: a transgastric cystogastrostomy in the cyst of 8 cm and a
      transduodenal punction in the cyst of 3 cm were performed, with an excellent
      postoperative result.

PMID- 1364947
TI  - Proposal of a hospital information system for a teaching hospital.

PMID- 1364948
TI  - [Compact disk-read only memory].
AB  - The new technology has made possible the new information methods development.
      Isn't erasable, it is compatible with personal computers, and without additional
      online charge. The CD-ROM, Compact Disc Read Only Memory. These electronic media,
      used in the information digital storage, come from the compact audio disc. One CD
      ROM covers over 250,000 text's pages, or 300,000 book's cards or 1,500 diskettes
      of 360 kbytes. In a compact disc there could be words, sounds, charts and images.
      MEDLINE database on compact disc, allows to search the current year on one CD
      ROM, covering over 300,000 citations from 3,200 publications, material drawn from
      both English and foreign language publications.

PMID- 1364949
TI  - Cytochemical localization of sorbitol dehydrogenase in kidney and liver from
      Myiopsitta m. monachus (Boddaert, 1783), during embryonic development.
AB  - A histochemical study to determine the localization of sorbitol dehydrogenase
      (SDH) in kidney and liver from embryionic, young and adult Myiopsitta m. monachus
      was performed. The enzyme activity increased with age in both organs. In the
      kidney, the enzyme appeared at the proximal convoluted tubules, and increased in
      the basal cytoplasm of the tubular cells. In the liver the localization was
      diffuse in the lobule but more intense in the cytoplasm of hepatocytes,
      especially in the perinuclear areas. These studies indicate that the cytochemical
      enzyme localization differs in this species, which is more evolutioned than
      Gallus gallus, and would be related to ontogenetic and phylogenetic
      differentiation.

PMID- 1364950
TI  - [Profile of spermatic morphology in normospermic and dyspermic patients].
AB  - The evaluation of spermatic morphology is of importance due to its prognostic
      value in potential male fertility, both in natural and in assisted reproduction.
      In the present work, the morphologic profile of samples of semen from normal and
      dispermic patients was determined, in order to establish a correlation between
      structure and function. Samples were obtained from male partners of infertile
      couples who attended andrologic consultation. The smears were stained by the
      Papanicolaou technique, and the criteria of the OMS and the recent modification
      of Kruger were followed to evaluate spermatic morphology. Of all the patients
      studied (n = 46), 35% were normospermics (A), 39% asthenospermics, 7%
      oligospermics, 2% terastospermics and 17% presented combined alterations. The
      average percentage of normal spermatozoa was of 23.7 +/- 1.23 in the whole
      population. When group A patients were compared with asthenospermics, significant
      differences were found in the percentage of spermatozoa with middle piece and
      tail alterations, in the last group (p < 0.02). Similarly, when samples were
      analysed according to the presence of alterations: none (A), one (B) two or more
      (C), it was observed that the percentage of normal forms decreased in the groups
      in that order (A < B < C); (A or B vs C p < 0.05). The percentage of tapering
      spermatozoa was significantly higher in group C (p < 0.01 vs A or B). From the
      above results, it appears that 1) the larger number of functional alterations is
      related to a higher percentage of structural anomalies, and 2) the deficient
      motility in the asthenospermic group, is associated to the middle piece and tail
      alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364951
TI  - Rubeosis iridis and neovascular glaucoma: I. Etiopathogenesis and treatment--the
      present state of the problem.
AB  - Rubeosis iridis is one of the severest complications of the occlusive diseases of
      retinal vessels associated with retinal hypoxia. In the pathogenesis of rubeosis,
      the author emphasizes the chronicity of retinal hypoxia which leads to the
      production of the vasoproliferative substance. This so-called vasoproliferative
      factor then induces the new formation of vessels on the retina, the optic disc,
      the iris and the anterior chamber angle. Neovascularization of the anterior
      chamber angle then very often results in the development of the prognostically
      very unfavourable neovascular glaucoma. It shows that the most effective methods
      of treatment of rubeosis iridis are the so-called coagulation techniques
      panretinal photocoagulation or cryocoagulation. By application of these
      techniques, we achieve the destruction of the anatomical substrate which is
      responsible for the production of the vasoproliferative substance, and the result
      is involution of rubeosis on the iris and in the anterior chamber angle.

PMID- 1364952
TI  - Rubeosis iridis and neovascular glaucoma: II. Our own experiences with the
      treatment by cryocoagulation.
AB  - The author evaluates the effect of two cryosurgical methods on the development of
      rubeosis iridis in neovascular glaucoma. In 12 eyes, cyclo-cryocoagulation was
      used as a single method, in 26 eyes, trans-scleral panretinal cryocoagulation was
      used in combination with cyclo-cryocoagulation in one session. Markedly better
      results were achieved by using the combined cryosurgical method. When trans
      scleral panretinal cryocoagulation was applied in combination with cyclo
      cryocoagulation, all the patients showed, 6 weeks postoperatively, a marked
      involution of rubeosis iridis. Complete regression of rubeosis iridis after cyclo
      cryocoagulation was achieved only in one eye. The insufficient regression of
      rubeosis iridis in neovascular glaucoma, after the performance of single cyclo
      cryocoagulation, the author explains in that way that by this surgical method
      only one component in the pathogenesis of rubeosis iridis is resolved. The author
      assumes that in the pathogenesis of rubeosis iridis in neovascular glaucoma, two
      components play their role: not only the underlying disease which conditions the
      development of proliferative retinopathy but also the high intraocular pressure
      which reduces the blood-flow in the retinal bed and thus increases retinal
      hypoxia.

PMID- 1364953
TI  - Painful eye in neovascular glaucoma and its treatment with cryocoagulation.
AB  - The author summarizes the present knowledge concerning the treatment of pain in
      neovascular glaucoma. The treatment of the pain is very closely connected with a
      good compensation of the intraocular pressure. The author did not find a
      correlation between the degree of the elevated intraocular pressure and the
      ocular pain. He compares the results of the treatment of ocular pain in
      neovascular glaucoma with cyclo-cryocoagulation as a single method with those of
      the method of trans-scleral panretinal cryocoagulation in combination with cyclo
      cryocoagulation performed in one session. In the treatment of ocular pain,
      markedly better results were achieved by using trans-scleral panretinal
      cryocoagulation in combination with cyclo-cryocoagulation. Complete relief from
      pain was achieved the fifth postoperative day in 54.5% when only cyclo
      cryocoagulation was performed, in 100% when trans-scleral panretinal
      cryocoagulation was carried out in combination with cyclo-cryocoagulation.
      According to the author, this stands in connection with the better compensation
      of the intraocular pressure after the combined cryosurgical intervention and, in
      all probability, also with the assumed analgesic effect of panretinal
      cryocoagulation, which is obviously due to damage to the sensitive nerves of the
      bulb during freezing of the sclera an the choroid.

PMID- 1364954
TI  - The nucleus raphe magnus of the cat. I. Quantitative analysis of neurons.
AB  - According to the shape of the perikarya six different types of the neurons in the
      nucleus raphe magnus of the cat were classified: spherical, oval, fusiform,
      pyramidal, piriform and stellate. According to size small, medium, large and
      giant cells were described. The spherical neurons are small and the most uniform
      in the shape and the stellate perikarya are the most variable in the shape and
      size.

PMID- 1364955
TI  - The visual outcome in neovascular glaucoma patients treated with cryocoagulation.
AB  - The outcome of visual acuity in neovascular glaucoma is generally speaking very
      poor and frequently the result is a blind and painful eye. The author summarizes
      the outcome of visual acuity in neovascular glaucoma after the treatment with two
      cryosurgical methods--cyclo-cryocoagulation as a single surgical method and trans
      scleral panretinal cryocoagulation in combination with cyclo-cryocoagulation at
      one session. In 38 eyes with acute neovascular glaucoma, cyclo-cryocoagulation as
      a single method was applied to 12 eyes and the combined cryosurgical method to 26
      eyes. The author has shown that the impairment of the visual acuity after acute
      elevation of intraocular pressure in neovascular glaucoma is very rapid. He
      estimates that the loss of visual acuity is reversible within one week after the
      acute elevation of the intraocular pressure. In eyes where the initial visual
      acuity is poor--fingers in front of the eye and worse--the hope to maintain the
      visual acuity for a longer period is small, and that despite the good
      compensation of the intraocular pressure. In 6 eyes where the visual acuity was
      relatively good (6/24-3/60) up to one week prior the operation, it was possible
      in 5 eyes to maintain the visual acuity (6/24-2/60) for at least 6 months by
      application of the combined cryosurgical method.

PMID- 1364956
TI  - Single fiber EMG in multiple sclerosis.
AB  - A group of 25 patients with sclerosis multiplex (SM) was examined by means of
      single fiber (SF) EMG. This group had the mean value of jitter 55.0 +/- 4.5
      microseconds and fiber density (FD) 2.15 +/- 0.12. The findings of the patients
      with the first attack of illness and the findings of the patients with twenty
      year duration are the same. A hypothesis is suggested that not only the
      peripheral neuron but also the CNS structures take part in the increase of
      jitter. The different results of stimulated single fiber (SSF) and SF EMG are
      discussed; the former reflects only the peripheral part of the nervous system due
      to peripheral stimulation. The higher levels of CNS cannot take part in it.

PMID- 1364957
TI  - Single fiber EMG in cerebrovascular stroke (CVS).
AB  - This paper gives previously unpublished data about fiber density (FD) and jitter
      in patients with CVS. The cluster of these values is very similar to that found
      in sclerosis multiplex (SM). There is a problem whether both clusters represents
      the same disorder of CNS compared with amyotrophic lateral sclerosis (ALS) or
      spinal muscular atrophy which have different values. Another problem is the
      participation of presumed central lesion on the increased jitter, the mechanism
      of which is still unknown.

PMID- 1364958
TI  - Tetanic syndrome and its examination.
AB  - The article presents a new electromyographic method; it describes the non
      invasive examination of tetany with surface electrodes. This method is more
      sensitive than the classical needle technique and, moreover, the necessity to use
      expensive disposable needle electrodes is avoided.

PMID- 1364959
TI  - The nucleus raphe magnus of the cat. II. Quantitative analysis of axosomatic
      synapses.
AB  - Quantitative analysis of axosomatic synapses in the nucleus raphe magnus of the
      cat showed great variations in their number, shape and size. There exist some
      relations between the size of perikarya and the number and size of the synaptic
      knobs. In the small neurons the number and size of synapses was smaller than in
      the large neurons, but there exist some exception from this rule. The observed
      morphological differences can be ascribed to different functional significance of
      various neurons.

PMID- 1364960
TI  - Enzymatic equipment of the developing human eye.
AB  - The activities of a number of enzymes seen in adults and in animal material were
      found in the anlage of the developing eye in relatively early stages. Using
      standardized methods according to Lojda, activities of the following enzymes were
      proved in cryostat sections of the 9 and 10-week eye: ALP, ACP, ATP, TPP, alpha
      GPDH and G6PDH. In 19-week eye moreover, positive reaction for DPP IV, ANE, CHE,
      ACHE was also detected, while G6PDH activity disappeared. In neither of the age
      categories SDH activity could be seen.

PMID- 1364961
TI  - Early prenatal development of the brush border enzymes in the embryonal
      intestine.
AB  - Standard methods were used for the study of the activity of brush border enzymes
      in the epithelium of the intestine of 45 human embryos aged from 4 to 22 weeks of
      the intrauterine life. Enzymes of the peptidase group (DPP IV, APM, APA, GGT,
      BBEP), of the phosphatase group (ALP, ACP, AMP, ATP), and of the disaccharidase
      group (saccharose, lactase, trehalase) were studied. In the embryonal
      developmental period (to week 8), the activity of proteases was mainly detected
      on the luminal surface of the primitive pseudostratified columnar epithelium of
      the intestine anlage. The highest activity was displayed by DPP IV. In the period
      from the 8th week, villi are formed from the duodenum up to the ileum. After week
      9, differentiation of Lieberkuhn crypts was observed. The activity of proteases
      was very high (DPP IV especially) in the differentiating microvillous zone of
      primitive enterocytes. Gradient of apex-base activity of the villus was maximal
      on the apex of villi. After week 12 of the intrauterine life, the activity of
      disaccharidases ALP and AMP occurs in the differentiating brush border, and a low
      activity of BBEP of the protease group is present.

PMID- 1364962
TI  - [Activity of gamma-glutamyl-transpeptidase in embryonic human organs].
AB  - The histochemical distribution of gamma-glutamyltranspeptidase (GGT) in organs of
      human embryos and fetuses was studied. In youngest embryos (4-7 weeks), a high
      GGT activity in the epithelium of the proximal part of embryonic intestine was
      recorded. Maximum of the activity was localised on membranes of luminal surface
      of primitive epithelium. High GGT activity in differentiating hepatocytes was
      also observed. In older fetuses (8-20 weeks) the activity of GGT gradually
      increases. In the epithelium of intestinal villi apex-basis gradient of the
      activity was recorded. The highest GGT activity in differentiating brusch border
      of the epithelium of proximale tubuli of fetal kidney was observed as well.

PMID- 1364963
TI  - [Quantitative evaluation of capillaries in the myocardium of human embryos].
AB  - On cryostat sections of hearts of human embryos and fetuses aged 7 to 20 weeks,
      the length, density and internal surface (area) of capillaries were studied in
      surface unit of the ventricular myocardium using a semi-automatic apparatus MOP
      AM 03. The DPP IV and ALP-positive capillary segments were evaluated separately.

PMID- 1364964
TI  - The effect of morphine on lymphocyte viability in vitro.
AB  - The effect of morphine on viability of the lymphocytes in peripheral blood,
      thymus and spleen of laboratory rats of the inbred Wistar strain was studied.
      Blood mononuclear cells for lymphocyte separation were obtained from the
      interface after Ficoll-Verografin gradient centrifugation. Lymphocyte suspension
      from the thymus and spleen was acquired by means of the Potter-Elvehjem
      homogenizer in icy Tyrod solution. Cell viability was studied by a simple method
      according to Hanks and Wallace after 6 hours incubation in normal oxygen
      atmosphere at 37 degrees C. Morphine reduced viability of the blood lymphocytes
      by 34%, of the spleen lymphocytes by 14% and the viability of the thymus
      lymphocytes was reduced by 18% in contrast to viability of the control group.

PMID- 1364965
TI  - Effect of morphine on phagocytic activity of the polymorphonuclears and
      monocytes.
AB  - The effect of morphine on the phagocytic activity of the polymorphonuclears
      (PMN), and monocytes in peripheral blood of laboratory rats of inbred Wistar
      strain was studied in vitro. Phagocytic activity of both types of the white blood
      cells was examined by the classical method using microspherical hydrophilic
      particles (Hema-particles), phagocytosis of the Hema-particles was determined by
      light microscopy. For evaluation of the leukocyte adherence, the method of
      MacGregor was used. Morphine was proved to influence phagocytic activity of
      individual types of the leukocytes in different way. Phagocytic activity of the
      PMNs was suppressed (by 14.0%), and that of monocytes was potentiated (by 17.1%).

PMID- 1364966
TI  - "Nude rabbit" with aplasia of B-lymphoid structures.
AB  - An original observation of the randombred nude rabbit with aplasia of B-lymphoid
      structures (absence of the follicles in lymph nodes and spleen, no Peyer's
      plaques). The thymus gland and the T-dependent structures in the spleen and lymph
      nodes were-on the contrary-well preserved. The nude skin of this genetic rabbit
      mutant contained large numbers of hair follicles showing almost intrafollicular
      retention of hairs with their subsequent dysplasia at the subepidermal and
      ostiopilar level.

PMID- 1364967
TI  - Lymphocyte proliferation and T-lymphocyte subsets during experimental
      immunomodulation of Balb/C mice by Olimunostim.
AB  - To objectivize possible immunomodulatory effects of polybacterial lysate
      Olimunostim (P. acnes, K. pneumoniae, S. aureus), splenic lymphocyte
      proliferation and T-lymphocyte subsets were followed-up in Balb/c mice
      administered perorally the lysate or saline (controls). The enhanced spontaneous
      lymphocyte proliferation observed at the beginning of Olimunostim application
      preceded a gradual increase of lymphocyte reactivity to T-mitogens reaching the
      maximum five days after the administration of the last dose and returning back to
      the control levels ten days afterwards. This stimulation of lymphocyte
      proliferation was accompanied by Olimunostim induced increase of CD4+ splenic
      lymphocytes being most pronounced five days after the end of immunomodulation and
      later returning to the initial values. The last experiment revealed an enhanced
      response of the in vivo primed lymphocytes after the re-exposure to Olimunostim
      in vitro. It is concluded that mostly nonspecific activation mechanisms,
      plausibly also parallelly induced specific immunity, are involved in Olimunostim
      modulatory effects on the cellular immune response.

PMID- 1364968
TI  - Study of modulatory effects of Olimunostim on cellular immunity in healthy
      humans.
AB  - To objectivize potential modulatory effects of polybacterial lysate Olimunostim
      on cellular immunity, the T-lymphocyte subpopulations and lymphocyte reactivity
      to mitogens were followed up in 10 healthy volunteers subjected to Olimunostim
      application and parallelly in 6 healthy individuals receiving placebo. The
      preparation, which was applied perorally in seven consecutive daily doses, had no
      effects on T-lymphocytes and their subpopulations and exerted only a limited
      influence on lymphocyte reactivity to mitogens. Both the moderate suppression of
      proliferative response to Con A and PWM, observed after the application of the
      three doses of Olimunostim, and the insignificantly enhanced response to PHA and
      Con A, revealed shortly after the last dose was given, were only of transient
      character and in comparison with the control group were not proved to be
      statistically significant. To explain the discordance of these results with the
      recently reported modulatory effects of Olimunostim on murine lymphocytes it is
      suggested, that the performed tests using the peripheral blood lymphocytes cannot
      mirror the processes developing in the diseased tissues. With respect to this
      presumption and also to the observations of enhanced immunomodulatory effect of
      Olimunostim on terrain altered by infection, it is proposed to investigate
      cellular immune parameters in specific disease sites of Olimunostim treated
      patients suffering from recurrent infections.

PMID- 1364969
TI  - Immunological profile of patients with recurrent respiratory infections.
AB  - The authors present an analysis of the results of laboratory immunological
      examination of 52 patients suffering from recurrent respiratory infections.
      Besides the typical laboratory correlates of chronic inflammation, several
      findings indicated the depressed function of cellular and partially humoral
      immunity. The immunological parameters, most frequently decreased in comparison
      with normal values, were as follows: the response to the recall antigens of
      Imunoskintest (lower in 54% of patients), the relative number of CD3+ lymphocytes
      (35%), the CD4/CD8 ratio (37%), phagocytic activity (37%) and also serum IgA
      (12%). This means that more than two thirds of patients displayed at the time of
      examination a substantial alteration of one or more immunological parameters, the
      depression of cellular immunity was much more pronounced. It is concluded that
      the laboratory immunological examination of patients with recurrent respiratory
      infections is very important for revealing of an underlying cause of the disease
      and for indicating the adequate immunomodulatory treatment.

PMID- 1364970
TI  - The preheparin and postheparin lipids of high density lipoprotein subfractions:
      relation to the serum insulin and postheparin plasma lipase activities in normal
      human.
AB  - The preheparin and postheparin lipoprotein lipids (cholesterol C and
      triacylglycerols TAG) were related to the serum insulin and to the postheparin
      plasma activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in
      normolipemic human. The positive correlation, although not statistically
      significant, of insulin level of the LPL activity was found, while no correlation
      to the HL activity was seen. Under preheparin conditions: 1) both insulin level
      and LPL activity were negatively related to the VLDL-C/TAG ratio indicating an
      enrichment of VLDL with TAG, 2) moreover, the LPL activity was positively related
      to the HDL-C and HDL3-C, 3) the HL activity predominated in relation to the HDL,
      and particularly to the HDL3, as indicated by negative correlations to the both
      lipids and to the lipid/apoA-I ratios of HDL and HDL3. This lipid depletion of
      HDL3 was more expressive due to the TAG, while HDL2 appeared to be relatively
      enriched with TAG, as suggested by correlations of C/TAG ratios with HL activity.
      The in vivo acceleration of lipoprotein metabolism by heparin resulted in: 1) the
      reduction of VLDL-TAG and HDL2-TAG, and in the increase of HDL3-TAG, 2) the
      appearance of positive relation of HDL2-C to the LPL activity and of opposite
      relation to the HL activity, 3) the lack of HL correlation to the TAG of HDL and
      HDL3. Even under these conditions no relation of insulin level to any HDL lipid
      was revealed. The results suggest that in normal human the HL affects more
      considerably than LPL the lipid metabolism of HDL subfractions and it does not
      seem to be under insulin control.

PMID- 1364971
TI  - Effects of static magnetic field on some pathogenic microorganisms.
AB  - A high power superconductive magnetostatic system MAGNEX was used by the authors
      for two microbial strains Escherichia Coli and Staphylococcus Aureus, the
      magnetic induction values were 0.5-4 T and the exposure time was 30-120 minutes.
      In this paper morphological traits, standard biochemical tests, sensitivity and
      effects influence of some chosen sorts of antibiotics are considered and
      evaluated here. All the above given criteria and facts were analysed and the
      authors have come to the conclusion that magnetic DC field has no significant
      influence on the growth, the biochemical activity as well as on the antibiotics
      effects on the strains examined.

PMID- 1364972
TI  - Fatty acids in lipids of nasoethmoidal polyps.
AB  - In 29 samples of recurrent nasoethmoidal polyps removed from 11 patients, the
      relative fatty acids composition was established by means of gas chromatography.
      Four samples of nasal mucosa of patients without polyps were subjected to the
      same procedure. A significant increase in the content of linoleic acid (18:2, n
      6) as well as in the index "linoleic acid/oleic acid" was found. Proportion of
      arachidonic acid was high both in polyps and in control samples of nasal mucosa.
      An orientation examination of fatty acids in individual fractions of lipids,
      compared to serum values, showed that the main source of arachidonic acid appears
      to be phospholipids.

PMID- 1364973
TI  - Quantitative indices in paternity cases.
AB  - The study discusses the basic quantitative indices used as a standard method in
      foreign professional literature dealing with paternity cases. They are as
      follows: 1. mean probability of exclusion (PE) which characterizes the
      informative value of the experts opinions and is the same in all the disputes
      evaluated by this expert. 2. relative frequency of men chosen at random from the
      population and excluded at given phenotype of mother and child (RME). 3.
      probability of paternity (PP) for particular trio: mother-child-the accused man.
      Hereinafter the results of our studies in the HLA laboratory in Olomouc from 1976
      1991 are introduced.

PMID- 1364974
TI  - HLA antibodies in renal transplant candidates.
AB  - The level of anti-HLA antibodies was followed in 155 patients of the chronic
      dialyzed program: against antigens HLA Class I and antigens HLA-DR representing
      HLA Class II. Correlation between the titre of these antibodies and additional
      factors were analyzed. The effect of pregnancy and consequently of sex was
      proved. Of significance were the number of dialyses undergone and the time of
      inclusion into the dialyses program. Positive correlation between the titre of
      both types of anti-HLA antibodies is so significant that it makes possible to
      concentrate on the more simple anti HLA I antibodies determination. The result of
      crossmatch test is of crucial importance when making decisions on suitable
      recipient of the kidney from the set of patients of dialyzed program (DP). The
      presence of anti-HLA alloantibodies can cause hyperacute rejection. The anti-HLA
      alloantibodies titre is regularly followed in DP patients. Several significant
      hypotheses can be verified in a large enough set of patients (hypotheses marked
      with ordinal numbers 1-5): 1. Only the titre of anti-HLA Class I antibodies is
      usually followed in DP patients. Some workplaces abroad consider it useful to
      follow even the anti-HLA Class II antibodies. Is anti-HLA I and HLA II antibodies
      titre in such a significant correlation that it is sufficient to follow only anti
      HLA Class I? 2. Mechanisms of HLA antigen sensitization in DP patients are well
      known. We can verify the influence of transfusion number, allograft rejections
      and number of previous pregnancies on the anti-HLA antibodies titre.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1364975
TI  - HLA-A and HLA-B typing: classification of errors.
AB  - The authors followed the frequency of errors in serologic identification of HLA-A
      and HLA-B antigens. They analyzed 205 paternity cases evaluated independently by
      two judicial experts (a revision of expert opinions). The specification of
      revealed discrepancies is demonstrated in the study and possible causes of their
      origin are analyzed. In the conclusions the authors recommend useful steps
      leading to the decrease of error frequency in HLA antigen typing. The HLA system-
      the major histocompatibility system of a man, has a broad utilization in the
      field of practical medicine. HLA compatibility should be respected in the choice
      of the couple donor-recipient for transplant therapy. HLA, as a highly
      polymorphic system, is successfully applied in forensic medicine. A strong
      association with some diseases makes it possible to utilize HLA as a supporting
      diagnostic sign. The commission for nomenclature of WHO at XI. International
      Histocompatibility Workshop (1991) recognized the following numbers of HLA
      specificities: 25 A, 55 B, 10 C, 21 DR, 9 PQ, 6 DP. At present HLA laboratories
      used mostly serological methods. The need to mutually differentiate HLA antigens
      which are similar due to their molecular structure puts an extraordinary demand
      on HLA laboratories. On one hand, a great number of HLA phenotypes exist in the
      population, which ensures the identification of every individual and the
      distinguishing of self-nonself components. On the other hand there appear the
      limited possibilities of HLA laboratories with relatively low numbers of
      diagnostic sera. We inquired how often errors occurred in HLA antigens
      determination. We chose a set of 205 auditing experts opinions of paternity cases
      for analyzing the problem.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1364976
TI  - Prescription of psychopharmaca in common psychiatric diagnoses (discussion on the
      results of an anonymous survey).
AB  - The authors have made an anonymous survey among Czechoslovak psychiatrists on the
      prescription of psychopharmaca in select psychiatric diagnoses. The first place
      is occupied by haloperidol, perfenazin and chlorpromazine in hallucinatory
      paranoid syndromes, amitriptyline and clomipramine in depressions. The authors
      also wanted to find out which drugs were regarded as unsuitable by each
      psychiatrist. The replies varied considerably. In comparison with a similar
      survey made ten years ago, the methods of treatment relatively persist and
      novelties are rather wished for than really administered.

PMID- 1364977
TI  - Vitamin E and A and periodontium in pregnant diabetics.
AB  - The authors followed physiological levels of vitamin E and A in four-week
      intervals in the course of physiological pregnancy in 11 insulin dependent
      diabetics. The highest mean levels of both vitamins were found in the IIIrd
      trimester. Simultaneously, the periodontal condition and the standard of oral
      hygiene were evaluated by means of epidemiological indexes in two-week intervals.
      The most marked inflammatory changes of periodontium occurred in the 8th month
      and were followed by an improvement before delivery, though the standard of oral
      hygiene was unchanged. The possibility of the eventual contribution of both
      vitamins in the improvement of periodontal condition in the final stage of
      pregnancy seems evident.

PMID- 1364978
TI  - Luminol-dependent chemiluminescence and the clinical course of multiple
      sclerosis.
AB  - The luminol-dependent chemiluminescence activity before and after the ACTH
      (Synacthen) treatment was investigated in multiple sclerosis patients and the
      dependence of the changes of chemiluminescence upon the disease course was
      evaluated. The tests were performed with granulocytes and monocytes in the
      presence or in the absence of autologous thrombocytes and, further, the activity
      of whole blood was tested. All the test were performed both without additional
      stimuli (spontaneous activity) and with opsonized zymosan. Of the parameters
      tested, only the spontaneous chemiluminescence activity of whole blood displayed
      an evidence of dependence on clinical course of the disease. In clinically
      improved patients a decrease of the whole blood chemiluminescence was found.
      Similar trend was observed in chemiluminescence of whole blood stimulated by
      zymosan and in spontaneous granulocyte activity in the presence of autologous
      thrombocytes. The results show that the whole blood chemiluminescence is
      decreased in improved patients and suggest that this decrease might be related to
      the leukocyte-thrombocyte interaction.

PMID- 1364979
TI  - [He created the life of a scholar and lived it fully].

PMID- 1364980
TI  - [Nature told him to be human].

PMID- 1364981
TI  - [Si vis pacem, para pacem instead of si vis pacem, para bellum].
AB  - In the article the danger of the nuclear war and its possible medical, biological
      as well as environmental consequences for the population of the whole world have
      been presented. War is determined by political, social and economic problems, but
      it need not be the only way of solving complex world conflicts. War is generated
      in human mind and it is only human mind which can prevent it. The world-wide
      organization called "International Physicians for the Prevention of Nuclear War"
      (IPPNW) was set up in 1981 to prove that it is better for the mankind to live in
      peace than to confront the nuclear peril. In case of the nuclear war health
      service would not be effective at all and the world's population should have no
      doubts about it. There is no doubt that the radiologists and other physicians,
      physicists working on radiation and other technical personnel are particularly
      responsible for popularizing in the society the knowledge of the basic physical
      facts and of the medical consequences of nuclear danger.

PMID- 1364982
TI  - The influence of selenium on the reproduction of rats.
AB  - Selenium is a vestigial element indispensable for man and animal, having adverse
      effects when in bigger quantities. Among the diseases resulting from selenium
      deficiency in animals the most important are nutritional muscular dystrophy,
      exudative disthesis (most common in poultry), and nutritional hepatic dystrophy.
      In the man chronic intoxication occurs most of all, which is observed in selenium
      bearing regions. Taking into consideration geographic distribution on some of the
      diseases beneficial influence of selenium is observed in cardiac and vascular
      diseases, and hypertension. The correlation between selenium deficiency and
      mortality caused by neoplasm is also notable. It is unquestionable that selenium
      inhibits the activity of enzymes, especially those containing sulfohydryl groups.
      The stabilization of lysosomal membranes leads to the presumption that selenium
      prevents peroxidation processes in tissues and cell membranes. The influence of
      selenium on reproduction is also worth noticing. Its supply turns out to be
      effective in cases of infertility of sheep, and partly in rats, pigs, and
      poultry. The embryo dies in pigs fed on fodder poor in selenium and vitamin E.
      The degeneration of the ovaries and placenta accretion occur in cows in cases of
      selenium deficiency. The excess of selenium can affect negatively the
      reproductive system. The element is thought to be a teratogenic agent. Since it
      permeates through the placenta and lactic gland easily, the symptoms of selenosis
      appear in new-born animals; many of them have developmental anomalies occurring
      at the same time. In birds the decrease in laying eggs and their incubation occur
      in case of selenium deficiency.

PMID- 1364983
TI  - Micro-element content in teeth with and without caries in people over 50 years of
      age.

PMID- 1364984
TI  - [Evaluation of the healing value of Iwonicz mineral water in balneo-climatic
      therapy of chronic hyperplastic laryngitis with wide pachydermic changes of
      laryngeal mucous membrane after microsurgery by the Kleinsasser method].
AB  - The paper comprises clinical estimation of using Iwonicz mineral water Elin 7 in
      balneotherapy of chronic hyperplastic laryngitis after its microsurgical therapy
      by Kleinsasser method. Investigation in the group of 246 people showed that
      combined treatment, i.e. microsurgery and balneotherapy, is an effective method
      of healing some hyperplastic inflammatory diseases of mucous membrane of the
      larynx.

PMID- 1364985
TI  - [Diagnosis of dental caries based on intra-oral roentgenograms].
AB  - On 238 intra-oral roentgenograms there were assessed carious process, shape,
      size, extent and depth of defects as well as the possibility of complications in
      teeth which were not treated. There were assessed 277 defects, out of which 194
      in upper teeth and 83 in lower ones. In all the teeth of the maxilla and of the
      mandible there was found the greatest number of amorphic defects and semilunar
      contact surfaces. There were also observed a lot of defects in radiciform
      cementum, thus, often under the gingivae. These are sites difficult for access
      for clinical examination. That is why radiologic examination is often conclusive
      in localizing carious process and in accurate diagnosing in the case of pulpitis
      going on.

PMID- 1364986
TI  - Dysplasia epiphysealis multiplex--problems in diagnosis and treatment of the hip.

PMID- 1364987
TI  - [Different departure and course of the right obturator artery].

PMID- 1364988
TI  - Communication accidents during the sixties and at the present time.

PMID- 1364989
TI  - Influence of Metizol ("polfa") on the liver of pregnant rats.
AB  - Drugs are the largest group of substances inactivated by the liver. They may have
      a stimulatory or inhibitory effect on the system of hepatic enzymes. Metizol is a
      thyrostatic belonging to the group of trimidazole derivatives. Its mechanism of
      action consists in inhibition of triiodothyronine++ and thyroxin secretion by the
      thyroid, owing to inactivation of the enzymes causing iodination of the thyrosine
      groups of thyroglobulin. This relatively little toxic drug when used for a
      prolonged period may lead to hyperaemia of the thyroid, and in pregnant women (by
      passing through the placenta) its side effects may threaten the foetus. The
      future mother affected with hyperthyroidism should receive full Metizol doses to
      avoid the danger of a thyroid crisis. A radical improvement of her health should
      be reached before childbirth.

PMID- 1364990
TI  - Histological and histochemical investigations of the influence of Metizol on the
      function of the kidneys when given during pregnancy.

PMID- 1364991
TI  - [Ultrastructure of epithelial cells of rat seminal vesicles in the period of
      functional transformation and puberty].
AB  - It was found that the ultrastructure of the epithelial cells of the rat seminal
      vesicles changes during the period of puberty. The changes consist in formation
      of the cell organelles that participate in the production of secretion and in
      differentiation of the epithelial cells into the secretory and basal cells. The
      complementary biochemical studies indicate the close relationship between the
      formation of the typical ultrastructure of the secretory glandular cells of
      seminal vesicles and the presence of fructose in the secretion of these glandular
      cells.

PMID- 1364992
TI  - [Histoenzymatic picture of rat gastric mucosa under the influence of
      dexamethasone].
AB  - White male [correction of female] rats were given Dexamethasone in a single dose
      0.35 mg/24 hrs. Group I was given the drug once, group II--received it for 2
      days, and group III--for 7 days. 24 hrs after the medicine had been given the
      mucous membrane of the stomach corpus was collected for examinations. There were
      performed: H+E staining, PAS reaction and histochemical reaction to the activity
      of ATP-ase, acid phosphatase and alkaline phosphatase. The results obtained were
      compared with those obtained in a group of control animals which were given
      distilled water. The administration of Dexamethasone did not affect significantly
      the activity of the examined hydrolases, however, it damaged the mucous barrier
      of the stomach, specially in the animals after 7 days of application of the drug.

PMID- 1364993
TI  - [Histochemical picture of kidneys from pregnant female rats subjected to the
      action of vibramycin].
AB  - Female rats were given intragastrically, by means of a probe, Vibramycine in
      suspension, in a dose 4 mg/kg body weight, in different stages of pregnancy. On
      kidney sections there were performed: H+E staining, PAS reaction, histochemical
      determination of enzymes activity: alkaline phosphatase, ATP-ase, SDH and LDH. In
      non-pregnant females receiving the drug there was observed an intensification of
      alkaline phosphatase activity in brush border of main tubules of the kidney and a
      slight broadening of the light of the tubules. In pregnant females receiving the
      drug, most clearly in the second half of pregnancy a slight intensification of
      the activity of the examined enzymes was observed.

PMID- 1364994
TI  - [Morphometric investigations of rat parotid gland after experimental encortone
      treatment].
AB  - The influence of Encortone treatment in the dose of 1 mg/kg of body mass on the
      secretory segments of male rat parotid gland was investigated. The changes of
      section area of cell nuclei, secretory cells, serous acini and changes of the
      number of cells in the acini were statistically analyzed. The observed changes
      depended upon the period of Encortone treatment. Seven-day Encortone treatment
      caused a statistically significant increase of the cell nuclei size and decrease
      of the cell and acini sizes. Changes of these parameters were result of cell
      hyperplasia and formation of new acini. Thirty-day Encortone treatment caused
      hypertrophy of cell nuclei, cells and acini of rat parotid.

PMID- 1364995
TI  - [A case of hydatidiform mole with an unclear clinical picture].
AB  - The authors presented the case of hydatidiform mole with unclear clinical
      picture. They discussed clinical difficulties in the diagnosing of that lesion,
      and stressed the role of US method in establishing the specific final diagnosis.

PMID- 1364996
TI  - The youth state of health in secondary and post-secondary medical schools all
      over the country.

PMID- 1364997
TI  - Relation between somatic development and some environmental factors in the male
      population of vocational mining schools in the Lublin Coal Basin.
AB  - Somatic development of a child, although genetically determined, depends also on
      the influence of biogeographic and socio-economic factors of the environment. The
      effects of these factors popular in the literature are seen in the differences of
      somatic development of children brought up in urban and rural environments. In
      comparison with urban population, country children are characterized by lower
      growth and body mass, delayed manifestation of sexual maturity, greater amount of
      incorrect posture features, worse state of nutrition and lower index of mental
      development. The differences in somatic development of children were also found
      while comparing the size of agglomeration and socio-professional factors
      determining parents' level of education and financial situation of the family.
      One could also observe the improvement of somatic development of children living
      in regions of quick and intensive urbanization and industrialization.

PMID- 1364998
TI  - Cardiovascular diseases risk factors in male population from mining vocational
      schools of the Lublin Coal Basin.
AB  - Contrary to certain industrial countries which secure an impressive decrease in
      coronary heart mortality, Poland has had, especially in the last decade, the
      significant increase of morbidity and mortality caused by cardiovascular
      diseases. Although this phenomenon concerns mainly the middle-age mean groups,
      special care for the whole population should be undertaken. The successful way to
      decrease the death rate and morbidity attributed to coronary heart disease (CHD)
      are the long-term prevention programs as for example Multiple Risk Factor
      Intervention Trial, Belgian Heart Disease Prevention Project, Lipid Research
      Clinics Coronary Primary Prevention Trial and others. Because there is some
      evidence that certain risk factors occur also among children, it seems that the
      effectiveness and efficacy of such prevention programs may be increased when
      started in the young population.

PMID- 1364999
TI  - Evaluation of lung function in male population from vocational mining schools of
      the Lublin Coal Basin.
AB  - Occupational exposure to dust and other environmental factors in coal miners may
      impair the lung function of workers. Besides the coal workers' pneumoconiosis,
      the inhaled dust may cause decreased ventilatory capacity as a due to chronic
      bronchitis (9, 13). The same diseases, especially chronic bronchitis, are common
      in general population and may arise not only from occupational reasons (11, 12).
      The involvement of the genetic factors, environmental pollutions and cigarette
      smoking should be considered.

PMID- 1365000
TI  - Evaluation of nutritional status of male population from mining vocational
      schools in the Lublin coal basin.
AB  - The basic nutritional mistake in Polish population at considerably rare
      deficiency of proteins and calories is incorrect composition of diet with the
      excess of animal fat and carbohydrates. Social and economic changes which
      influence living conditions result in the change of diet whose trends are not
      always correct. The problem is the quality of food products, contamination of
      pollution due to industrialization and the use of chemicals in agriculture, and
      inadequate proportion in the essential food components or supply of the
      indispensable trace elements. The other problem is overnutrition leading to
      obesity which is one of risk factors in civilization diseases (8, 11). The
      nutritional status depends on the level of education and economic situation of
      different social groups. It is expected that among the pupils of vocational
      mining schools who usually come from numerous peasant and working class families
      nutritional mistakes may occur very often. It denotes both malnutrition and
      incorrect proportion in consumption of proteins, animal fats and carbohydrates.
      On the other hand, the expected changes in social and economic status due to a
      good job create new conditions for proper nutrition. An additional factor which
      should be taken into account are nutritional requirements resulting from specific
      character of underground work.

PMID- 1365001
TI  - [Analysis of caries dynamics in permanent teeth of children 6-9 years old from
      Lublin].
AB  - The stomatological examination was carried out in 443 children aged 6-9 years
      including 203 boys and 240 girls. It was ascertained that the prevalence of
      caries of permanent teeth in children aged 6 was 3.64%, aged 7-50.88%, aged 8
      73.53% and aged 9-76.81%. The DMF index in children aged 6 was 0.05, aged 7
      1.375, aged 8-1.852 and in those aged 9 it was 2.308. There was noticed some more
      advancement in caries process in girls than in boys.

PMID- 1365002
TI  - [Sensitivity to antibiotics of Salmonella isolated from patients].

PMID- 1365003
TI  - [Histochemical and histologic examination of kidney from white rats after
      experimental administration of dexamethasone].
AB  - Kidneys of the rats which had been intragastrically administered Dexamethasone
      (10 mg/kg), were examined. Observations were carried out after a single and twice
      repeated application of the preparation, as well as after 7 days of everyday
      administration. It was found, on the basis of histological and histochemical
      observations (reaction to alkaline phosphatase activity, reaction to acid
      phosphatase activity, PAS-method staining), that both single and twice
      administration of Dexamethasone do not cause the damage of the kidney parenchyma,
      whereas after 7 days of everyday application of the preparation irreversible
      changes can be observed.

PMID- 1365004
TI  - [Histopathologic and histochemical examination of rat liver after prolonged
      experimental application of potassium bichromate].
AB  - The rats were given potassium bichromate (K2Cr2O7) in dose of 2 and 5 mg/kg of
      body weight and magnesium chloride (MgCl2) in dose of 500 mg/kg for a period of
      30 days. The two compounds were also given conjointly (K2Cr2O7-5 mg+MgCl2-500
      mg). There were carried out histopathological as well as histochemical
      examinations of acid phosphatase activity, alkaline phosphatase activity and
      adenosine triphosphatase activity in the liver. With small doses (2 mg) of
      potassium bichromate no changes have been stated. With larger doses (5 mg) of
      potassium bichromate an increase of histochemical reaction to acid phosphatase as
      well as forming of histopathological changes such as parenchymatous degeneration,
      steatosis of hepatocytes and their necrobiosis have been observed. There has not
      been found any protective action of magnesium chloride on the cytotoxic activity
      of potassium bichromate on the liver cell.

PMID- 1365005
TI  - [Effect of potassium dichromate on histopathologic changes in testicles of white
      rats and results of atomic pilograms on fur].
AB  - Male rats were administered, for the period of 30 days, potassium dichromate
      (K2Cr2O7) in a dose of 2 and 5 mg/kg of body weight and magnesium chloride (Mg
      Cl2) in a dose of 500 mg/kg of body weight. These two substances were also
      administered jointly (K2C2O7-5 mg/kg and MgCl2-500 mg/kg of body weight). In the
      testicles of animals receiving K2Cr2O7 in a dose of 5 mg/kg of body weight in
      groups III and IV there were observed changes of significant degree, mainly
      degenerative and multifocal, which consisted in degenerative changes of various
      degrees and changes of necrotic epithelium cells which, in turn, consist in cell
      hyper- or hypochromasia of chromatolysis or pycnosis and, too, in lesions of
      testicle epithelium of the spermatic epithelium cells. The cells of the Leydig
      intraparenchymatous gland did not reveal any histopathological changes as well as
      changes in the increase of hyatochemical tests. The highest concentration of
      chrome was in the hair of the animals receiving K2Cr2O7 in a dose of 5 mg/kg of
      body weight.

PMID- 1365006
TI  - My service in the Gulf War.

PMID- 1365007
TI  - Preliminary report of the significance of ultrasonography (US) in clinical
      practice.

PMID- 1365008
TI  - [Effect of pharmacologic blocking of the antigen-antibody reaction in adult
      respiratory distress syndrome (ARDS)].
AB  - In the experimental model of ARDS in rats there was investigated the influence of
      Intal (Fisons, GB) on the changes in the rat's lungs. Intal was inhaled through
      the respiratory system. Morphological examinations were carried out by
      hematoxylin and eosin staining. The results of experiment show that Intal seems
      to be a protective remedy in ARDS.

PMID- 1365009
TI  - Search behavior in various breeds of adult dogs (Canis familiaris): object
      permanence and olfactory cues.
AB  - Human analog tests of object permanence were administered to various breeds of
      adult dogs (Canis familiaris). Experiment 1 showed that the performance of
      terriers, sporting, and working dogs did not differ. Dogs succeeded in solving
      invisible displacement problems, but performance was lower than in visible
      displacement tests. Familiarity with the task had some influence because
      invisible displacement tests were more successful if they were preceded by
      visible displacement tests. In Experiment 2, odor cues from the target object and
      the hiding screens were available or were masked. Results confirmed that success
      was lower in invisible than in visible displacement tests and that these problems
      were solved on the basis of representation of visual information rather than on
      the basis of olfactory cues or of local rule learning. Dogs are compared with
      other species that display Stage 6 object permanence.

PMID- 1365010
TI  - Activity of antibiotics against resistant Pseudomonas aeruginosa.
AB  - The activity of 12 antibiotics, piperacillin, cefazolin, cefotiam, ceftizoxime,
      latamoxef, ceftazidime, cefuzonam, amikacin, ofloxacin, imipenem, aztreonam and
      minocycline, against 120 isolates of Pseudomonas aeruginosa was examined. In
      addition, the efficacy of antibiotics against single-, double-, or triple-drug
      resistant isolates of P. aeruginosa were also examined to determine the cross
      resistance to each drug. There was cross-resistance between piperacillin,
      ceftazidime and aztreonam, but amikacin and imipenem remained effective
      antibiotics, especially as salvage therapy, against isolates resistant to one
      agent. Results also suggested that piperacillin, ceftazidime or imipenem in
      combination with amikacin are effective combination regimens against most
      clinical isolates of P. aeruginosa. Amikacin and imipenem were also suitable
      antibiotics, especially as salvage therapy, against isolates of P. aeruginosa
      resistant to two agents. In conclusion, the results provide useful guidelines for
      choosing an effective treatment against clinical isolates of P. aeruginosa, and
      for choosing salvage therapy against resistant P. aeruginosa.

PMID- 1365012
TI  - Copulatory behavior, reproduction, and sperm competition in two strains of male
      rats.
AB  - Long-Evans males fathered 72% of the offspring when one Long-Evans and one F344
      male mated repeatedly with the same female throughout her estrus. When each male
      was restricted to one ejaculation and the second male was allowed to begin mating
      immediately following the first male's ejaculation, the second male left more
      offspring in each strain. However, the proportion was significantly greater for
      Long-Evans males. In contrast, there were no strain differences in either number
      of pregnancies or litter size in noncompetitive matings limited to two
      ejaculations, the minimal number required to induce pregnancy. The only
      consistent behavioral differences were the greater number of intromissions
      performed with shorter latencies by F344 males, differences that cannot readily
      be used to explain their reduced success. It was hypothesized that the two
      strains may differ in the adequacy of penile reflexes used to form, set, or
      dislodge sperm plugs.

PMID- 1365011
TI  - Ceftazidime and amikacin as empiric treatment of febrile episodes in neutropenic
      patients in Saudi Arabia.
AB  - Sixty-four consecutive febrile episodes in 50 consecutive patients with
      malignancy and neutropenia were empirically treated with a combination of
      ceftazidime and amikacin. Of 52 analysable episodes, the response rate was 59.6%
      overall and 26.3% of episodes with microbiologically documented infections with
      septicaemia. Infection-related death occurred in 10 patients (19.2% of episodes).
      The response rates were similar in patients with acute leukaemia or other
      malignancies. Poor response is attributed to increased frequency of infections
      with Gram-positive and fungal organisms. A modified empiric regimen including
      cover for Gram-positive and fungal organisms is suggested in similar patient
      populations.

PMID- 1365013
TI  - Morphological variability and developmental aspects of monkey and human granule
      cells: differences between the rodent and primate dentate gyrus.
AB  - The postnatal generation, dendritic development and morphological variability of
      granule cells were studied in the monkey and human dentate gyrus. Granule cells
      are mainly formed prenatally in primates with an approximate 4- to 6-month
      postnatal generation time in humans. Dendritic development of individual granule
      cells appears to be prolonged over a long period of time. Immature granule cells
      were observed as late as in 15-month-old children. The morphological variability
      of granule cells is similar in monkeys and humans. Both display granule cells
      with basal dendrites as well as granule cells with different dendritic lengths
      and spine densities. The prolonged development of the spine structure of the
      human mossy cells suggests that synaptic connections between granule cells and
      their postsynaptic target neurons develop through a long postnatal period of time
      that may last as long as 5 years postnatally. The morphological variability of
      granule cells in primates should be considered when drawing conclusions about
      hippocampal neuropathology. The prolonged development of the neurons and neuronal
      circuitries in the human dentate gyrus may cause the lack of adult-like memory
      formation in early childhood resulting in the phenomenon of 'infantile amnesia'.

PMID- 1365014
TI  - Cyclophosphamide mobilization of peripheral blood stem cells for use in
      autologous transplantation after high-dose chemotherapy: clinical results in
      patients with contaminated or hypocellular bone marrow.
AB  - Peripheral blood stem cells (PBSC) can be used for hematopoietic reconstitution
      in patients who have received high-dose chemotherapy (HDC). Previously, we
      reported 18 such patients who had nonmobilized PBSC harvested in steady state. We
      have now performed PBSC reinfusion in 24 patients with hypocellular or tumor
      involved marrow who received cyclophosphamide (Cy) mobilization (4 grams/m2)
      prior to PBSC collection. The PBSC were collected upon rebound hematopoietic
      recovery by continuous-flow leukapheresis and subsequently cryoproserved. A
      median of 3.17 x 10(8) mononuclear cells/kg (range 1.47-3.95 x 10(8)) were
      collected. Patients underwent a median of 6 apheresis procedures (range 5-12). To
      date all 24 patients have undergone PBSC reinfusion after HDC. Fourteen patients
      received post-reinfusion granulocyte/macrophage colony-stimulating factor.
      Granulocyte recovery (> 500 x 10(6)/ml) has occurred at a median of 13.5 days
      (range 7-39) and platelet recovery (> 50 x 10(9)/ml without transfusion support)
      has occurred in 20 patients at a median of 33 days (range 7-121 days). Four other
      patients have platelet counts of greater than 20K and are transfusion
      independent, but have still not achieved counts of 50K. PBSC collection after Cy
      mobilization is feasible and effective for hematopoietic reconstitution after HDC
      and reinfusion. All 24 patients demonstrated trilineage engraftment. Although
      neutrophil recovery was not significantly hastened (as compared with our
      nonmobilized or steady-state data), time to platelet engraftment was
      foreshortened.

PMID- 1365015
TI  - Graft engineering: the evolution of hematopoietic transplantation.
AB  - In vivo therapeutic manipulation as well as ex vivo grafting are important
      strategies for bone marrow manipulation and transplantation. This review article
      discusses the early techniques for marrow processing and manipulation as a
      background for discussing later graft engineering protocols, as well as
      preclinical and experimental protocols designed to modify transplantation biology
      at the multidisciplinary level. The direction of future trials in graft
      transplantation is also discussed.

PMID- 1365016
TI  - Immunomagnetic manipulation of hematopoietic cells: a review of current
      technology.
AB  - During the last decade, immunomagnetic separation of cells has become popular due
      to the simplicity and speed of the technology. A variety of magnetic materials
      have been developed that have fundamentally different characteristics. Some of
      these act as true colloids and have the properties of solutions, while others are
      larger and are based on the polymerization of materials, such as styrene, in the
      presence of magnetite. In this article, the different magnetic matrices are
      discussed and reviewed with respect to their use for the separation of cells of
      the hematopoietic system. Additionally, a brief introduction into the field of
      immunomagnetic separation of nucleic acids is presented, as this technology may
      be used to perform investigations at the molecular level on hematopoietic cells.

PMID- 1365017
TI  - Purging of autologous bone marrow for transplantation: the protection and
      selection of the hematopoietic progenitor cell.
AB  - Autologous bone marrow transplantation (ABMT) is the treatment of choice for
      selected patients with acute myelogenous leukemia, non-Hodgkin's lymphoma, and
      poor prognosis breast cancer. A possible limitation of this approach is that
      clonogenic tumor cells could be collected and infused back into the patient along
      with the normal bone marrow. The major emphasis in our laboratory has been the
      development of marrow purging regimens for breast cancer patients. This paper
      describes two investigative approaches hematopoietic progenitor cell protection
      and selection. We describe how the use of G-CSF in the patients who receive
      positively selected marrow shortens the rate of engraftment.

PMID- 1365018
TI  - Quantitation of tumor cell removal from bone marrow: a preclinical model.
AB  - We have developed a multiassay system consisting of fluorescence microscopy,
      immunocytology and tumor colony assay to monitor the removal of tumor cells from
      bone marrow. This system was tested in preclinical purging experiments in which
      neuroblastoma cells were seeded into bovine marrow and purged by treatment with
      monoclonal antibodies and immunomagnetic beads. Eight experiments were performed
      on two different neuroblastoma cell lines seeded at 2% and/or 5% contamination.
      We consistently demonstrated greater than a 3 log removal with one cycle of
      antibody/bead treatment and greater than a 1 log further reduction by addition of
      a second cycle. We also demonstrated removal of all detectable tumor stem cells
      by this purging method. We feel that this system will prove valuable for
      monitoring ex vivo tumor removal in future clinical studies and should be
      considered for use in other purging trials.

PMID- 1365019
TI  - Interferon-gamma potentiates the antitumor effect of cyclosporine-induced
      autoimmunity.
AB  - Graft-versus-host-disease (GVHD), which results after allogeneic bone marrow
      transplantation (BMT), is associated with reduced leukemic relapse. This may be
      mediated by an immunologic attack with subsequent destruction of residual tumor
      cells. On the other hand, GVHD does not normally occur after autologous BMT
      (ABMT), which has an inherently high relapse rate. However, an autoimmune
      syndrome (AIS) similar to GVHD can be induced after autologous/syngeneic BMT by
      administration of cyclosporine-A (CsA), resulting in the production of major
      histocompatibility complex (MHC) class II or Ia autoreactive cytolytic effector
      cells. Since many hematopoietic malignancies express variable levels of class II
      molecules, we hypothesized that the adjuvant use of interferon-gamma (IFN-gamma)
      with CsA-induced autoimmunity after autologous/syngeneic BMT may upregulate class
      II antigens on residual tumor cells and make them more susceptible to attack by
      the Ia-reactive cells of CsA-induced AIS. The present studies demonstrated that
      the CsA-induced autoimmune syndrome mediated an anti-tumor effect, although this
      effect was dependent on challenge with a minimal number of tumor cells. Further
      studies clearly demonstrated that the antitumor effect could be markedly enhanced
      by administration of IFN-gamma which increased the susceptibility of the tumor to
      recognition and lysis by the CsA induced autoimmune effector cells. The induction
      of MHC class II-restricted AIS similar to GVHD by administration of CsA together
      with the ability to manipulate the surface phenotype of residual tumor cells may
      lead to decreased relapse rates in the ABMT setting.

PMID- 1365020
TI  - Initial trial of bispecific antibody-mediated immunotherapy of CD15-bearing
      tumors: cytotoxicity of human tumor cells using a bispecific antibody comprised
      of anti-CD15 (MoAb PM81) and anti-CD64/Fc gamma RI (MoAb 32).
AB  - The high-affinity receptor for IgG, Fc gamma RI, expressed on monocytes and
      interferon-gamma (IFN-gamma)-stimulated neutrophils, is a trigger molecule for
      cell-mediated cytotoxicity. We have prepared murine monoclonal antibodies (MoAb
      22 and MoAb 32) that bind to Fc gamma RI outside the ligand binding site and thus
      bind to and trigger cytotoxicity that is not competed by other immunoglobulins.
      Because of these properties, it seemed that these MoAbs would be very useful for
      the development of bispecific antibodies (BsAb) for targeting normal cellular
      immune defense mechanisms as a new form of immunotherapy for treatment of cancer.
      BsAbs incorporate into a single molecule the binding specifities of two different
      antibodies, and, thus, can be used to target myeloid cells to tumors, ensure
      activation of cellular cytotoxic mechanisms, and target cell lysis and/or
      phagocytosis. BsAbs were prepared using anti-Fc gamma RI MoAb and an anti-myeloid
      cell MoAb, PM81, reactive with the CD15 antigen, for studies of antibody
      dependent cellular cytotoxicity. Conjugates were made by cross-linking sulfhydryl
      groups of Fab fragments of MoAb 32 or 22 (both IgG1) and sulfhydryl groups added
      to intact PM81 (an IgM) using N-succinimdyl-acetyl-S-thioacetate (SATA). The
      resulting product was purified by high-performance size-exclusion chromatography.
      The ability of the BsAbs to mediate attachment of human monocytes to tumor target
      cells was confirmed in a microtiter well assay of binding of MTT-labeled U937
      cells (a human Fc gamma RI-bearing cell line) to SKBR-3 (PM81-reactive breast
      carcinoma) target cells. The ability of the BsAbs to mediate killing of HL-60
      promyelocytic leukemia cells was studied using a 6-hour Chromium-51 release
      assay. Effector cells were monocytes obtained by cytopheresis and cultured for 18
      hours with IFN-gamma. Monocytes alone caused minimal killing (5-20%), monocytes
      plus BsAb caused moderate killing (20-50%), and monocytes plus BsAb plus human
      serum resulted in maximal killing (50-80%). Experiments were performed to test
      the ability of the BsAb to purge bone marrow of small numbers of leukemia cells
      using bone marrow mononuclear phagocytes treated for 18 hours with IFN-gamma
      prior to adding target cells. Without the addition of human serum as a source of
      complement, a 90% depletion of clonogenic HL-60 cells could be demonstrated. With
      human complement, up to 95% depletion was seen. Thus, this BsAb possessed the
      ability to lyse tumor cell targets by two different mechanisms, complement and
      cell-mediated lysis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1365021
TI  - Processing and storage of human bone marrow: do we know enough to set guidelines,
      standards, and regulations?

PMID- 1365022
TI  - Animal models for human hematopoiesis.
AB  - Despite seminal contributions provided by in vitro studies to the field of
      hematopoiesis, our present knowledge of mammalian lymphohemopoiesis and the
      mechanisms governing differentiation and self-renewal of hematopoietic stem cells
      has been derived in most part from elegant in vivo studies. The inability to
      apply such an approach to the examination of the human hematopoietic system is
      the primary reason why several aspects of human hematopoiesis including human
      stem cell biology are still poorly understood. To overcome the inability to probe
      human hematopoiesis in vivo, researchers have "humanized" animals via the
      transplantation of human hematopoietic progenitor cells and other tissues in an
      attempt to create human-animal chimera suitable for investigating human
      lymphohematopoiesis in vivo. To date, several of these "humanized" animal models
      have been developed. During their relatively short existence, human-animal models
      have contributed substantially to the field of experimental hematology. The
      development, peculiarities, shortcomings, and applications of these animal models
      as well as their potential use in exploring the field of human
      lymphohematopoiesis are the focus of this review.

PMID- 1365023
TI  - Retroviral vector-mediated gene transfer into hematopoietic cells: prospects and
      issues.
AB  - Gene therapy is a developing technology that may allow the treatment of a variety
      of congenital and acquired genetic disorders as well as infectious diseases
      through the introduction of exogenous genetic material into relevant cellular
      populations. Currently, the most effective method for gene transfer into cells of
      the hematopoietic system is with retroviral vectors. Appropriate cellular targets
      for gene transfer include totipotent hematopoietic stem cells as well as long
      lived lineage committed cells such as T lymphocytes. Although retroviral vector
      mediated gene transfer into totipotent stem cells and subsequent long-term
      expression of transduced genetic material in stem cell progeny has been observed
      in murine bone marrow transplantation experiments, similar observations have not
      been made in clinically relevant large-animal models. A number of recent advances
      in gene delivery systems, purification of stem cells, defining extramedullary
      sources of stem cells, characterizing the biologic processes that regulate the
      proliferation and developmental potential of stem cells, and construction of more
      effective models for assessing stem cells, may result in improvements in gene
      transfer into large animal and human totipotent stem cells.

PMID- 1365024
TI  - Umbilical cord and placental blood hematopoietic stem cells: collection,
      cryopreservation, and storage.
AB  - Human umbilical cord and placental blood is a rich source of hematopoietic stem
      cells that can be used to reconstitute hematopoiesis after intensive
      myeloablative therapy. Therefore, it has become necessary to develop techniques
      for (i) collecting large volumes of umbilical cord aseptically, (ii) optimizing
      the yield of viable cells after cryopreservation and thawing, and (iii)
      minimizing the risk of maternal T-cell contamination. Our protocol for the
      collection, cryopreservation, storage, and transport of human umbilical cord and
      placental blood is described in detail.

PMID- 1365025
TI  - Enumeration of cells in bone marrow and peripheral blood stem cell collections:
      technical issues and prospects for standardization.
AB  - Enumeration of total nucleated cells and mononuclear cells is a fundamental part
      of the laboratory evaluation and quality control program for bone marrow and
      peripheral blood stem cell collections intended for transplantation. Measurement
      of the total nucleated cell content is especially useful for providing rapid
      feedback about the bone marrow product during or immediately after the harvest.
      However, the mononuclear cell content may be more informative because the
      nucleated cell population contains a variable number of mature granulocytes and
      nucleated red cells, which do not contribute to hematopoietic engraftment. The
      lack of comparative data among various laboratories and among different types of
      cell counting methods has hindered standardization of these assays among bone
      marrow processing laboratories. Specific issues needing attention in assay
      standardization include sample preparation and handling, identification and
      elimination of artifacts in automated counting, relative advantages and
      disadvantages of manual and automated counting methods, and criteria for
      differential counting of nucleated cells. The establishment of standards for bone
      marrow and other stem cell counting methods, as well as other evaluation
      procedures, should be preceded by collection and analysis of comparative data,
      and followed by a proficiency testing program for bone marrow processing
      laboratories.

PMID- 1365026
TI  - Autologous graft engineering.
AB  - Autologous transplantation of bone marrow or peripheral blood stem cell
      preparations is now a widely used form of rescue from the myeloablative effects
      of high-dose therapy for malignant disease. The success of this procedure is
      affected by numerous factors associated both with management of the patient and
      the quality of the graft. In this review, approaches are described to maximize
      the success and utility of this therapeutic approach.

PMID- 1365027
TI  - The regulation of hematopoietic stem cell collection and storage: the New York
      State approach.
AB  - In December 1988, the New York State (NYS) regulatory code on bone marrow banking
      went into effect. The goals of the regulations were to codify a high standard of
      practice, to prohibit charlatanism in the practice or promotion of stem cell
      banking, and to promote legitimate research. The NYS approach modeled the stem
      cell regulatory language after that already established for blood banks and
      clinical laboratories. Also, the stem cell standards are an element of standards
      applicable to all tissue banks, developed as a result of a comprehensive
      transplant law enacted in NYS in 1990. The code itself, published as an addendum
      to this article, mandates that a qualified (by training and experience) medical
      director and medical advisory committee be appointed, and gives broad and
      complete responsibility for the services provided to that medical director.
      Explicit written policies and procedures regarding administrative, technical,
      safety, and quality issues are necessary, but regulatory micromanagement of the
      laboratory was avoided by limiting detailed procedural requirements. We believe
      that these regulations have contributed to the quality and safety of stem cell
      related therapies in NYS.

PMID- 1365028
TI  - Bone marrow and peripheral blood stem cell harvesting.
AB  - A number of malignant diseases are responsive to supralethal myelotoxic high-dose
      chemoradiotherapy, and can be treated with hematopoietic stem cell rescue. The
      number of genetic diseases correctable by replacement of defective pluripotent
      stem cells with normal stem cells or through gene transfer is ever-increasing. In
      all these cases, pluripotent hematopoietic stem cells need to be infused, which
      can be obtained directly from the bone marrow or from the peripheral blood with
      or without the aid of mobilizing strategies. This article is a detailed review of
      the technical and medical aspects of stem cell collection from the bone marrow
      and the peripheral blood.

PMID- 1365029
TI  - The risk of tumor cell contamination in peripheral blood stem cell collections.
AB  - Peripheral blood stem cell (PBSC) reinfusions are being used with increasing
      frequency in lieu of, or in addition to, autologous bone marrow transplantation
      (ABMT) to rescue cancer patients from the myeloablative effects of high-dose
      chemotherapy. However, the incidence and quantity of tumor cell contamination in
      PBSC collections has not been widely investigated. This paper reviews the
      existing data and presents new information to demonstrate that tumor cells are
      detectable in PBSC harvests from patients with a variety of malignancies.
      Furthermore, their presence in peripheral blood may have prognostic and clinical
      significance. Areas of future research and applications for PBSC technologies are
      also discussed.

PMID- 1365030
TI  - Hematopoietic stem cell cryopreservation: a review of current techniques.
AB  - Hematopoietic stem cells (HSC) can be stored for prolonged periods at cryogenic
      temperatures. The techniques currently used were derived from the initial report
      in 1949 of cryopreservation of bovine sperm in glycerol. The addition of this
      penetrating cryoprotectant protected the cells from the injury associated with
      ice formation. Current cryopreservation techniques (with minor variations)
      suspend cells in an aqueous solution of salts, protein, and one or more
      cryoprotectants. Cells are frozen at slow rates and stored generally below -120
      degrees C in mechanical freezers or nitrogen refrigerators. That these techniques
      are successful in maintaining HSC viability is evident from the engraftment of
      these cells in patients treated with marrow-lethal conditioning regimens.
      However, issues such as the composition of the cryoprotectant solution, cell
      concentration during freezing, cryoprotectant toxicity, and storage temperatures
      have not been adequately studied, primarily because of a lack of appropriate
      assays for HSC cryosurvival. HSC cryobiology will become an increasingly
      important subject as new HSC collection and processing techniques are developed.
      Improved cryosurvival of HSC using modified cryoprotectant solutions may improve
      engraftment kinetics and decrease the cost and morbidity of autologous
      transplantation.

PMID- 1365031
TI  - Ex vivo expansion and differentiation of hematopoietic stem cells.
AB  - Hematopoietic stem cells are phenotypically very heterogeneous, probably
      reflecting the degree of activation and/or differentiation. This cell population
      is capable of high-level proliferative activity and multilineage differentiation.
      Despite its potential for self-renewal, the hematopoietic stem cell exists in a
      quiescent state for prolonged periods of time. The mechanism(s) involved in
      triggering these cells to enter the cell cycle is/are not totally clear; however,
      cytokines (both positive and negative regulators) are implicated. Most, if not
      all known cytokines that interact at the stem cell level do so not only by
      inducing proliferation but also differentiation. The ability to maintain a
      population of truly primitive stem cells for extended periods of time in vitro is
      currently under investigation by many research groups.

PMID- 1365032
TI  - Recombinant human granulocyte-macrophage colony-stimulating factor stimulates
      superoxide anion and hydrogen peroxide production in human neutrophils.
AB  - The effect of purified recombinant human granulocyte-macrophage colony
      stimulating factor (GM-CSF) on the oxidative metabolism of human peripheral blood
      granulocytes was investigated. The respiratory burst of granulocytes was assessed
      in individual cells by flow cytometry utilizing the oxidation of the
      nonfluorescent 2',7'-dichlorofluorescein (DCFH) to the highly fluorescent DCF by
      hydrogen peroxide (H2O2). Treatment with GM-CSF caused granulocytes to produce
      H2O2 without addition of a second stimulus. The amount of H2O2 produced
      correlated with the concentration of GM-CSF administered. Also, GM-CSF did not
      prime the granulocytes for enhanced H2O2 production in response to N
      formylmethionyl-leucyl-phenylalanine (f-MLP). Consecutive stimulation of
      granulocytes with GM-CSF and f-MLP resulted in additive production of H2O2. GM
      CSF also induced granulocytes to release superoxide anion (O2-) in a dose
      dependent manner, when the respiratory burst was assessed by a conventional
      cytochrome c reduction assay. In contrast to hydrogen superoxide production, GM
      CSF significantly (p < 0.001) enhanced f-MLP-stimulated release of superoxide
      anion over that expected from the additive effects of the two agonists.

PMID- 1365033
TI  - Bone marrow processing with the Fresenius AS 104: initial results.
AB  - Prior to purging, cryopreservation, or ABO-incompatible bone marrow (BM)
      transplantation, we have concentrated 23 BM harvests using a modification of the
      "grancollect-protocol" and the recently available bone marrow stem cell (BMSC)
      protocol of the Fresenius AS 104 cell separator with the P1-Y set. Within 40-70
      minutes, the initial marrow volume of 922 ml (+/- 408 ml) was processed two to
      three times. A mean of 59% (+/- 20%) of the initial mononuclear cells was
      recovered in a mean volume of 119 ml (+/- 31 ml). The recovery of clonogenic
      cells, measured by CFU-GM assays, was 98% (+/- 80%). Red blood cells in the BM
      concentrates were reduced to 8% (+/- 4%) of the initial number. The procedure was
      efficient and yielded a BM cell fraction suitable for purging, cryopreservation,
      and transplantation. All transplanted patients showed fast and sustained
      engraftments after autologous or allogeneic BM transplantation.

PMID- 1365034
TI  - Counterflow centrifugal elutriation: experimental and clinical applications.
AB  - Counterflow centrifugal elutriation (CCE) separates mixed cell populations into
      distinct subpopulations, on the basis of different sedimentation characteristics,
      without impairment of cell function or yield. The advantages of this technique
      are the high recovery and viability of fractionated cells, as well as the
      rapidity and the reproducibility of results. CCE alone, or in combination with
      other separation methods, can provide homogeneous populations of cells for
      further investigations. Recently, CCE was employed in clinical studies aimed at
      preventing graft-versus-host disease in bone marrow transplant recipients, by
      depleting lymphocytes prior to bone marrow infusion. This article reviews the
      principles of elutriation and describes the possible experimental and clinical
      applications of this technique, which seems suitable for both peripheral blood
      (PB) and bone marrow (BM) separation.

PMID- 1365035
TI  - Colony-forming unit culture of bone marrow and peripheral blood stem cells:
      comparison of commercially available media.
AB  - Increased utilization of the granulocyte-macrophage colony-forming unit (CFU-GM)
      assay for quality control, dosing, and clinical investigation of peripheral blood
      (PB) stem cell and bone marrow (BM) products led us to compare two commercially
      available media ("Ready-Mix" [RM] from Terry Fox, Vancouver, Canada and Stem Cell
      CFU Kit [SCCK]) from GIBCO, Grand Island, NY-Baxter Healthcare Corp., Deerfield,
      IL) to our standard laboratory media (SLM). Aliquots of mononuclear cells (MNC)
      from PB and BM donors were cultured in triplicate in the three media and CFU-GM
      and erythroid burst-forming units (BFU-E) were enumerated. Similar colony growth
      was achieved in all media for PB; modestly increased BM CFU-GM were noted in
      SCCK. SCCK and RM are easy to use, are commercially available with lot-controlled
      conditioned media (PHA-LCM), and may facilitate the standardization of CFU assays
      in blood banks and bone marrow processing laboratories.

PMID- 1365037
TI  - The relationships between nonverbal intelligence and the strength of left-hand
      preference in left-handers to sex and familial sinistrality.
AB  - The relationship between the strength of left-handedness and spatial reasoning
      ability was studied in left-handed male and female subjects with and without
      familial sinistrality (FS). The degree of left-handedness was assessed by the
      Edinburgh Handedness Inventory. The spatial reasoning ability was measured by
      Cattell's Culture Fair Intelligence Test. It was found that there was a negative
      linear correlation between nonverbal IQ and the strength of left-handedness in
      females with and without FS, a quadratic relationship in male left-handers
      without FS and a positive linear correlation in male left-handers with FS. These
      results indicate that the brain may exhibit different patterns of cerebral
      organization in left-handers to sex and FS. It was concluded that the "crowding"
      hypothesis may apply only to a subgroup of left-handers, i.e., females with a
      greater bilaterality of cognitive functions than males.

PMID- 1365036
TI  - Clinical and experimental approaches to varieties of memory.
AB  - Memory is described as a complex aspect of cognitive functioning. Memory is
      dependent upon input from the sensory modalities; it relies upon the passage of
      time; and it requires intervening processes for initial acquisition and
      subsequent access. Based upon questions posed concerning the relationship between
      clinical and experimental advances in memory and memory disorders, an example is
      given to illustrate the influence of research upon techniques for diagnosis and
      rehabilitation. Suggestions are provided about how to approach answering other
      related questions in neuropsychology. An integrated program is suggested with the
      aim of bringing together findings from neuroanatomy, neurochemistry, and
      neurobehavior. Emphasis is placed upon integrating results of research based upon
      human and nonhuman models of disordered memory and other cognitive functions.
      Neuroanatomical systems important for performing delayed-reaction tasks are
      reviewed, as are results of delayed response and delayed alternation testing in
      several human populations with neurological dysfunction suggestive of frontal
      lobe damage.

PMID- 1365038
TI  - A straight nasal septum and right unilateral hypertrophied inferior nasal
      turbinate, a very rare anatomical phenomenon, in skilled language translators:
      relevance to anomalous dominance, brain hemisphericity and second language
      acquisition.
AB  - Research on second language acquisition has recently focused on the concept of
      brain hemisphericity. Since the nasal cycle indexes brain hemisphericity and a
      deviated nasal septum itself affected by structural brain dominance may prevent
      nasal cycling, we investigated the presence of septal deviation and inferior
      turbinate hypertrophy in 11 expert translators. We found that 10 of the 11
      subjects demonstrated both a straight nasal septum and right unilateral inferior
      turbinate hypertrophy, an extremely rare anatomical phenomenon. The one-tailed
      binomial test was extremely significant (p < .0000001). This anatomical
      phenomenon, which can be noninvasively checked in less than 30 seconds may
      predict excellence in second language acquisition.

PMID- 1365039
TI  - Muscle morphometry in amyotrophic lateral sclerosis.
AB  - Quadriceps muscle biopsies from 24 patients with amyotrophic lateral sclerosis
      (ALS) and 15 age-matched controls were prepared for histochemistry and analyzed
      morphometrically. Pathological features for denervation and reinnervation were
      observed in most ALS patients, although considerable variation between patients
      was noted. Myopathic changes were also seen in one-third of the cases. The
      morphometric data were not only related to the duration and mean diameter of type
      I fiber, but also to the duration and hypertrophy factor of type II fiber,
      suggesting that the progression and severity of ALS depends on the preservation
      of both fibers.

PMID- 1365040
TI  - The clinical assessment of attention.

PMID- 1365041
TI  - Maturation rate and spatial, verbal, and musical abilities: a seven-year
      longitudinal study.
AB  - We traced spatial, verbal and musical abilities through a seven-year period of
      adolescence. When we started our study, 60 boys had reached a mean age of 11.72,
      60 girls were 11.52 on average. Menarche and mutation served as markers for
      maturation. We found that early, mid, and late maturers differed on spatial
      orientation and on tactile-visual discrimination as measured with the Witelson
      task. No differences between the maturational groups emerged on verbal fluency
      and on Wing's Standardized Tests of Musical Intelligence. At some stages, sex
      differences on spatial, verbal, and musical tests emerged, and disappeared at
      others. The sex differences in performance levels were not associated with a sex
      specific relationship between maturation rate and performance levels. We found
      indications of the usefulness of sex hormone measurement in relation to cognitive
      and musical development in adolescence.

PMID- 1365042
TI  - Functional impairment of the rat superior colliculus after kainic acid
      intraocular injection: a 2-deoxyglucose study.
AB  - Long Evans rats monocularly injected with the kainic acid (KA), were exposed to
      "tonic" (diffuse steady light, stationary pattern, total darkness) and "phasic"
      (flashing, moving pattern) stimulations. By means of the autoradiographic 2
      deoxyglucose (2DG) technique we assessed the functional activity of the Superior
      Colliculus (SC) contralateral to the injected eye as compared to the normal eye
      SC. In the control SC all "tonic" stimulations determined low 2DG uptake not
      modified by the intraocular KA injection. On the contrary, "phasic" stimulations
      elicited a strong 2DG consumption in the normal SC, with a peculiar pattern of
      distribution depending on the kind of stimulus. Considering the total 2DG uptake
      as the added intrinsic and afferent metabolism, KA was able to affect only the
      latter, decreasing two-fold that expected for the afferent input loss. These
      findings can suggest a possible KA effect on off-line ganglion cells and, on the
      other side, they confirm the role of the SC in discriminating "phasic" and sudden
      phenomena from "tonic" and continuous ones.

PMID- 1365043
TI  - Serum testosterone levels in male and female subjects with standard and anomalous
      dominance.
AB  - Serum testosterone levels were determined in female and male subjects. Hand
      preference was assessed by the Edinburgh Handedness Inventory. Subjects with
      anomalous dominance (left-handers, mixed-handers, and right-handers with familial
      sinistrality) were compared to subjects with standard dominance (right-handers
      without familial sinistrality). The mean serum testosterone levels were found to
      be significantly higher in subjects with anomalous dominance than those with
      standard dominance. It was concluded that the results are in accord with the
      testosterone hypothesis of cerebral lateralization.

PMID- 1365045
TI  - Muscle derived motoneuron trophic factors promote the survival of motoneurons in
      vitro only when serum is present in the growth medium.
AB  - Motoneuron cultures were established from E6 chick spinal cord. Motoneurons
      survived for less than 2 days in chemically defined medium. The addition of
      muscle extract to the medium supported the survival of only a small portion
      (approximately 2%) of motoneurons for 8 days in vitro. A similar low survival
      rate was observed when the growth medium was supplemented with serum. The
      addition of muscle extract to serum containing medium resulted in the survival of
      about 20% of the motoneurons for 8 days. No differences were seen in the ability
      of tissue extracts prepared from E8 hindlimb, or muscle obtained from E11, E15,
      E18 and P3 chicks to support motoneuron survival in the presence of serum. It is
      apparent that although there are trophic factors present in muscle that support
      motoneuron survival in vitro, the actions of such trophic factors are dependent
      upon the presence of yet other factors found in serum.

PMID- 1365044
TI  - The relationship of pineal calcification and melatonin secretion to the
      pathophysiology of tardive dyskinesia and Tourette's syndrome.
AB  - Despite current intensive research, the pathophysiology of tardive dyskinesia
      (TD), a serious neurological side effect of neuroleptic treatment, is poorly
      understood. Prompted by the observation of an increased incidence and severity of
      abnormal perioral movements in neuroleptic-treated pinealectomized, as compared
      to intact rats, we suggested that the pineal gland exerts a protective effect
      which mitigates against the development of TD and, by inference, that reduced
      melatonin secretion may be related to the pathophysiology of TD. To investigate
      this proposition further, we studied the association of TD with pineal
      calcification (PC) on CT scan in chronic schizophrenic patients. Our findings
      revealed a significant association between TD and PC and suggest, furthermore,
      that PC may be a neuroradiological marker of TD. Since PC may reflect diminished
      secretory activity of the gland, these findings support the hypothesis that the
      pathophysiology of TD is linked to disturbances of melatonin secretion. The
      clinical and therapeutic implications of these novel findings are discussed. In
      the following communication, in which we introduce the hypothesis that
      disturbances of 5-HT and melatonin secretion are related to the pathophysiology
      of TD. Subsequently, we present a series of studies which relate to the
      association of TD with PC. We conclude by presenting the hypothesis that
      disturbances in melatonin secretion may also be relevant to the pathophysiology
      of Tourette's syndrome.

PMID- 1365046
TI  - Contrast responses to bright slits of visual cells in the superior colliculus of
      the albino rat.
AB  - Contrast is the most effective stimulus in the visual system. The response of
      single cells to changes in stimulus contrast has been studied in a large variety
      of animals and the contrast response function determined. In the rat, studies on
      responses to contrast have been focused primarily in the geniculocortical pathway
      and there are relatively few in subcortical structures. We report here for the
      first time the contrast response function of single units located in the superior
      colliculus (SC) of the albino rat to several stimulus contrast. Cells in the SC
      require a relatively high contrast to elicit a reliable response and the dynamic
      response range is restricted to a short contrast interval.

PMID- 1365047
TI  - Magnetic fields and seasonality of affective illness: implications for therapy.
AB  - Seasonal affective disorder is characterized by recurrent winter depression
      associated with hypersomnia, overeating, and carbohydrate craving. The severe
      form of winter depression affects about 5% of the general population and is
      believed to be caused by light deficiency. About 70%-80% of patients with winter
      depression experience attenuation of symptoms when exposed to bright light
      therapy. Hypotheses pertaining to the pathogenesis of winter depression implicate
      the effects of light on different characteristics of circadian rhythms. One of
      the environmental factors which may be implicated, in addition to light, in the
      pathophysiology of winter depression is the geomagnetic field. There is strong
      indication that the pineal gland is a magnetosensitive system and that changes in
      the ambient magnetic field alter melatonin secretion and synchronize the
      circadian rhythms. In man, shielding of the ambient magnetic field significantly
      desynchronizes circadian rhythms which could be gradually resynchronized after
      application of magnetic fields. The strength of the environmental magnetic field
      diminishes during the winter months, leading to increased susceptibility for
      desynchronization of circadian rhythms. Thus, since the acute application of
      magnetic fields in experimental animals resembles that of acute exposure to light
      with respect to melatonin secretion (i.e., suppression of melatonin secretion),
      magnetic treatment might be beneficial for patients with winter depression. In
      addition, since the environmental light and magnetic fields, which undergo
      diurnal and seasonal variations, influence the activity of the pineal gland, we
      propose that a synergistic effect of light and magnetic therapy in patients with
      winter depression would be more physiological and, therefore, superior to
      phototherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1365048
TI  - Comparison of eye movement patterns of dreaming and arousal in sleep.

PMID- 1365049
TI  - Oral syndrome: an incomplete form of cheiro-oral syndrome?
AB  - Cheiro-oral syndrome is a sensory disturbance observed around the corner of the
      mouth and the palm of the hand on the same side. We had an opportunity to observe
      a patient in whom sensory disturbance was limited only around the corner of the
      left mouth but not the hands or other findings. Computed tomography of the brain
      showed a low density area in the right thalamus. Could our case be called oral
      syndrome: incomplete form of cheiro-oral syndrome? We have to ask whether the our
      case is an oral syndrome or whether our case has to be regarded as a thalamic
      infarction.

PMID- 1365050
TI  - Complex sensory cross integration deficits in a case of corpus callosum agenesis
      with bilateral language representation: positron-emission-tomography and
      neuropsychological findings.
AB  - A 45-year-old right-handed patient with total callosal agenesis and absence of
      the anterior commissure was examined neuropsychologically and with magnetic
      resonance and positron emission tomography (PET with 18FDG) of the brain. PET
      results showed, in the resting state, a bilateral metabolic reduction in the
      hippocampal formation and a left hemispheric reduction in the amygdala, thalamus
      and in the occipital and temporoparietal junction areas of the cerebral cortex.
      Under speech activation hypermetabolic glucose activity was observed bilaterally
      in the region of the Wernicke area and within the left Broca area.
      Neuropsychologically, on the whole the patient behaved normally, the exceptions
      being an inability to associate olfactory stimuli with words, a clear left ear
      advantage in dichotic listening, and a similar high performance in recognizing
      verbal stimuli presented tachistoscopically to either hemisphere. From comparing
      the patient's behavior with that of other acallosals it appears that highly
      individual variants of cerebral organization and/or reorganization result from
      the lack of the brain's main commissural system and that the processing of
      sensory information deviates considerably especially in cases in whom the two
      main telencephalic commissures--corpus callosum and anterior commissure--are
      absent.

PMID- 1365051
TI  - Decerebrate rigidity with preserved cognition and gait: a possible role of anoxic
      ischemic brain damage.
AB  - A case of stable decerebrate posture in the upper limbs following sudden loss of
      consciousness and prolonged coma is described. The patient recovered most of her
      cognitive functions and gait, without clinical, neurophysiological or
      neuroradiological evidence of brainstem lesion. MRI shows borderzone infarcts. It
      is suggested that anoxic-ischemic cortical damage, affecting specially
      corticoreticular neurons, could explain the development of decerebrate rigidity
      in patients without apparent brainstem lesion.

PMID- 1365052
TI  - Concurrence of familial amyotrophic lateral sclerosis with Ribbing's disease.
AB  - We describe a case of familial amyotrophic lateral sclerosis associated with
      Ribbing's disease. This association has not been previously noted in the
      literature. The unusual feature of the case was that symptoms coexisted for
      several years before a correct diagnosis was made. The diagnosis was based on the
      clinical picture and the result of muscle biopsy and extensive radiographic
      study. This case serves to illustrate the fact that a separate problem should be
      considered when the clinical picture is not compatible with the underlying
      diagnosis.

PMID- 1365053
TI  - [Supplementary feeding--additional food in daily infant nutrition].
AB  - A group of 707 children aged 1 to 24 months from the territory of Vojvodina (10
      rural and urban settlements) was examined regarding additional food (nonmilk and
      milk food), time of introduction, infant's age and frequency of consumption. It
      has been concluded that supplementary feeding, including all food, starts early.
      Fruit and vegetable are introduced at the age of 34 months. As for the
      introduction of yolk (first given at about 4 months) it differs from the modern
      attitudes regarding the intake of this food. Milk formulae, meat and chicken
      liver are usually introduced about the fifth month. Analyses of the type of food
      and the way of preparation point to some extremities. Special emphasis is given
      to the environmental specificities which determine the recommendations.

PMID- 1365054
TI  - [Morphologic characteristics of the liver allograft in experimental warm
      ischemia].
AB  - Thirty-minute normothermic liver ischemia causes swelling of the hepatocytes and
      sinusoid wall cells, their individual necrosis and discharge of the glycogen
      supply in the hepatocytes. The swelling of the hepatocytes and of the sinusoid
      wall cells causes a significant reduction of the liver lobe sinusoid volume which
      decreases from 27.6% to 5.4%, representing, actually, one fifth of the normal
      value. Such finding was recorded as a critical vascular liver volume, because any
      further decrease of the sinusoid volume would inevitably lead toward manifest and
      persisting portal hypertension which evidently interferes with Bernoulli trial of
      the hepatitic perfusion. The obtained data determine morphofunctional relevancy
      of the liver allograft for transplantation and are useful for all other surgical
      interventions requiring partial resection of this organ or time limited regional
      and total ischemia.

PMID- 1365055
TI  - [Effect of polychemotherapy in the treatment of patients with non-Hodgkin's
      lymphoma].
AB  - Non-Hodgkin lymphomas belong to malignant hemopathies where clinical course,
      histological manifestation and therapy response are characterized by diverse
      features. Sensitivity of the lymphoma to chemotherapy introduced drug
      combinations for the improvement of patient survival rate and the prognosis. The
      study reviews the results achieved in 85 patients with NHL treated with different
      cytostatic combinations (COP, CHOP, COP-BLAM, MEV, LRS-074/B). The majority of
      the patients (41%) had entered the IV clinical stadium (Ann Arbor) with serious
      histological types of the disease (LDLL-45% and histiocytic 27%). This made us
      decide on LRS-074/B protocol (34%) and COP-BLAM cure (20%) planned for those with
      the advanced clinical stage and poor histological type of the disease. The full
      remission was achieved in 50%, partial in 28% of the cases while in 20% of the
      treated patients the therapy response lacked. Relapse of the disease occurs in
      about 50% of the treated patients. Patients treated with LRS-074/B protocol (p <
      0.05) live statistically significantly longer. In a period of 24 months 50% of
      those treated with LRS-074/B protocol, COP and COP-BLAM cures show no symptoms.
      There is no a statistically significant difference regarding the mean survival
      rate (p > 0.05) in relation to the histological type of the disease.

PMID- 1365056
TI  - [The effect of intermittent deep hypoxia on the adrenal gland cortex].
AB  - Wister laboratory rats were subjected to decreased atmospheric pressure occurring
      at the height of 23000 feet every day during 4 days and every second day during
      11 days. The effect of hypoxia on the adrenal cortex and biochemical blood
      factors in rats, sacrificed at different times after the completion of exposure
      to hypoxic conditions was investigated. The hypoxic stress elicited alkalosis
      when Pa O2 and Pa CO2 were decreased, while the saturation oh hemoglobin by
      oxygen was enhanced. The animals, which were exposed to hypoxia for 4 consecutive
      days, better endured the whole course of the experiment than those ones exposed
      every second day. The histological changes in the adrenal cortex were stronger in
      the animals exposed to the experimental conditions with two-day breaks. The
      intensity, character and reversibility of the changes depended much more on the
      rhythm of exposure than on the rhythm of sacrifice.

PMID- 1365057
TI  - [Typhoid fever--case report].
AB  - The paper describes a case treated at the Department of Infective Diseases in
      Novi Sad admitted during the remittance of typhoid fever. The course of the
      disease was atypical. Epidemiological and clinical features resembled those found
      in malaria but laboratory findings gave the true diagnosis. We found the case
      interesting because the diseased patient moved around a lot, making contacts with
      many people. Fortunately, contact diseases never happened to occur.

PMID- 1365058
TI  - [Foreign bodies in the esophagus in children].
AB  - The study describes 3 children with strange foreign bodies in the esophagus, one
      aged 14 the other two 8 and 13 months respectively. A metal hanger hook was found
      in the first one, a lollypop with a plastic stick 10 cm long in the second and a
      painting brush 21 cm long in the third one. Two of the foreign bodies were
      removed ambulatory, the third one hospitally. The interventions were not followed
      by complications.

PMID- 1365059
TI  - [Polycystic ovary disease: clinical picture, diagnosis and methods of therapy].
AB  - The study presents clinical features of polycystic ovaria with an incidence
      analysis of certain symptoms relevant for the diagnosis. Essential hormone
      parameters are showed, used for basal status evaluation, as well as
      endocrinologic tests applied for the determination of the causes of the disease
      within differential diagnostic investigation. Besides, in the differential
      diagnosis, possible diseases which should be excluded when diagnosing polycystic
      ovaria are showed. In the therapeutic protocol the stress is given to the methods
      used for the treatment of increased body hair, menstrual disorders and for
      ovulation induction. In the treatment of increased body hair cosmetic and
      medicamentous therapies are showed. In the ovulation induction method the
      application of clomiphene citrate, glycocorticosteroids, human menopausal
      genadotropins and a pulsatile pump for LHRH, have been analyzed in details.
      Moreover recent experiences in ovulation induction using LHRH analog (buserelin)
      and somatostatin analog (SMS) 201-995) are reported. Medicamentous ovulation
      induction was compared with surgical methods used for the induction (wedge
      resection and ovarial electrocauterization) pointing to the advantages and
      disadvantages of each method.

PMID- 1365061
TI  - [Sudden sensorineural hearing loss of unknown origin].
AB  - The study presents the results of a ten year experience in the treatment of
      abrupt hearing loss of unknown etiology in 248 patients. More successful
      treatment was achieved in patients with lesser degree of perceptive hearing
      reduction and those showing no vestibular symptomatology. A decisive factor for a
      favourable hearing recovery is time between the onset of the disease and the
      beginning of the therapy. Having this in mind, the authors insist on early
      diagnosis and early administration of drugs affecting the inner ear perfusion.

PMID- 1365060
TI  - [The metabolic X syndrome--4 case reports].
AB  - The study reviews current knowledge about metabolic X syndrome characterized by
      android obesity, arterial hypertension, insulin resistance with hyperinsulinemia
      and disturbed carbohydrate tolerance, a decrease of HDL cholesterol and an
      increase of the triglyceride rich VLDL particle level. The study describes 4
      female patients having been diagnosed for this syndrome. Only an ontime and
      vigorous reduction of overweight, along with intensified physical activity can
      prevent later development of serious complications, first of all, in
      cardiovascular system.

PMID- 1365062
TI  - [Malignant epilepsy in children: therapy with high doses of intravenous
      immunoglobulin].
AB  - 22 children with intractable childhood epilepsy (ICE) showing no response to
      conventional drugs of hormone (ACTH, Synacten) therapy were administered i.v.
      immunoglobulin (ENDOBULIN immuno) at a dosage of 400 mg/kg on the first and 15th
      day and subsequently every 3 weeks for 6 months. 12/22 patients showed IgG2
      subclass deficiency. A significant reduction in attacks, or even absence of
      attacks was observed in 13/22 children after 6 months of i.v. immunoglobulin
      therapy. Most of this children showed IgG2 subclass deficiency. The reduction of
      attacks after i.v. immunoglobulin therapy correlated with the improvement or
      normalization of the EEG finding. As for the psychomotor development, no major
      changes were noticed with respect to the condition prior to the therapy, but in
      children with IgG2 deficiency, there is no further psychomotor deterioration. 6
      months after the last i.v. immunoglobulin dose positive therapeutic effect
      remained in 5/22 children, with 3 children the therapy was repeated because of
      recidive attacks and worse EEG findings, and proved effective. Light worsening of
      the EEG findings was found in 3/22 children, 2/22 dropped out, 1/22 child died of
      intercurrent infection, and in girl the attacks ceased entirely 4 months after
      the last i.v. immunoglobulin dose. With other children the condition remained
      unchanged. According to the authors opinion, i.v. immunoglobulin has its own
      place in ICE treatment, and it is evident in all cases where the classical
      antiepileptic and/or hormone therapy was unsuccessful, especially in children
      with IgG2 subclass deficiency, that is, in all the epilepsy cases where a great
      number of attacks is imperilling the psychomotor development in children,
      independently of type.

PMID- 1365063
TI  - [The most common problems in differential diagnosis at the Outpatient Infectious
      Diseases Clinic in Novi Sad].
AB  - The most frequent differential diagnostic problems in the work of specialist for
      infective diseases were noticed and observed during several years at the out
      patient clinic of the infective department. They are classified according to
      clinical syndromes. The most frequent are icterical, gastroenterocolitical, rash
      and meningeal syndromes, then follow lymphadenitis colli, anginas, status
      febrilis and pertussis syndrome. The aim of presentation is to point out the most
      frequent errors in physician's practice.

PMID- 1365064
TI  - [Primary health care and corresponding health technology in clinical practice].
AB  - The aim of the study was to find out what general practitioners know and perform
      in the primary health care. The interview comprised 22% of all general
      practitioners from the region Novi Sad. The results obtained show that general
      practitioners have knowledge about definition, content of the work, about their
      role and what should be done according to the principles of the primary health
      care. But their knowledge, especially on methods of health education and methods
      of early diagnosis of risk factors and diseases are not fully applied during
      routine work. In order to achieve their role as a key persons for health strategy
      general practitioners must be educated for programme work, for intersectoral
      coordination, for monitoring and evaluation of the results of their work.

PMID- 1365065
TI  - [Drug therapy of nocturnal enuresis].
AB  - Bed wetting is a disorder the origin of which different authors find in different
      etiopathogenetic mechanisms. Depending on the etiologic concept different
      therapeutic methods have been used. Treating bed wetting, authors claiming that
      the basic cause is a disorder in the integration of central vegetative functions
      and sleep, most frequently administer anticholinergic agents, making use of their
      marginal central anticholinergic effect and their impact on sleep phases. For
      children who wet in bed, having an urodynamic disorder and the disordered
      function of the pelvic floor musculature, effective drugs would be those with
      peripheral anticholinergic effects as well as pelvic floor musculature
      reeducation exercises. In conformity with the current understanding of the bed
      wetting etiology due to disordered Adiuretin excretion circadian rhythm, the
      applied drug is synthetic Adiuretin. It has been pointed out that bed wetting,
      being a heterogeneous group of disorders, should be etiologically classified by
      additional diagnostic methods, and that the treatment should include aimed
      etiological therapeutical methods.

PMID- 1365067
TI  - Circumpolar Health 90. Proceedings of the 8th International Congress on
      Circumpolar Health. Whitehorse, Yukon, May 20-25, 1990.

PMID- 1365066
TI  - [Risks for neonates born in the breech presentation].
AB  - A prospective study included 106 females and their newborns, 45 of them born in
      breech presentation and 61 delivered normally. The incidence of prepathologic and
      pathologic CTG records and meconial amniotic fluid is significant (0.01), more
      frequent in breech presentation (24.44% and 22.2%) than in normal deliveries
      (8.20% and 9.84%). Children born in breech presentation have significantly (p <
      0.005) lower Apgar score values after the 1st and 5th minute than the control
      children. Infants born in breech presentation have significantly (p < 0.01) lower
      pH values (7.25 +/- 0.093) than those delivered normally (7.30 +/- 0.056). The
      acidosis incidence (pH < 7.20) in the studied group was 26.66% and 3.38% in the
      control group. In early neonatal period the disease occurred in 35.55% of the
      breech presentation group and 9.83% of the normal group (p < 0.01). In the
      control group there was no intracranial hemorrhages and manifest cerebral
      disfunction--complications most frequently involved in perinatal morbidity of
      children born in breech presentation (17.77% and 8.88%). One (2.22%) child born
      in breech presentation died in the early neonatal period.

PMID- 1365068
TI  - A brief discussion of the development of Native owned health provider agencies in
      Alaska within the context of anticipated health and systems issues.
AB  - The Self-Determination Act brought about an explosive growth of tribally run
      programs in Alaska during the 1970s at the same time that the Alaska Native
      Claims Settlement Act was being implemented. Tribes demonstrated great creativity
      in blending IHS with other sources of funds to develop more effective and more
      acceptable delivery of services to their people. Further, the tribes in Alaska
      have demonstrated great aptitude in developing effective lobbying techniques with
      the United States Congress, such that they have actually been able to increase
      their funding base beyond what was assumed at the time of takeover from the IHS.
      However, several problems loom on the horizon. First, there is the problem of
      cost shifting within the IHS which contains the potential that tribes opting not
      to take advantage of the Self-Determination Act may be victimized by those who
      do. Second, there is the problem of too few resources to serve too many patients,
      which from time to time, propels the Indian Health Service toward an attempt to
      change the rules with respect to eligibility for services. Finally, the ability
      of the Indian Health Service (and by extension, its contract tribes) to provide
      an adequate level of services to American Indian and Alaska Native clients is
      being dramatically eroded by the same inflationary forces that are driving the
      larger system of health care in the United States toward the brink of disaster.

PMID- 1365069
TI  - The health service in Greenland.

PMID- 1365070
TI  - Community health and health promotion in Baffin Island.

PMID- 1365071
TI  - Primary care morbidity in Labrador, 1986.

PMID- 1365072
TI  - The Canada-Alaska Health Agreement--a practical approach to developing cross
      border links.

PMID- 1365073
TI  - A new medical agreement for the Soviet Far East, Alaska, Magadan, Chukotka.

PMID- 1365074
TI  - Circumpolar medical research: the Siberian-Canadian context.

PMID- 1365075
TI  - The Cree Board of Health and Social Services of James Bay: the first twelve
      years: 1978-1990.

PMID- 1365077
TI  - Institute of Internal Medicine, Siberian Branch of the USSR Medical Academy:
      international research programs in Chukotka.

PMID- 1365076
TI  - Hospital morbidity in Labrador, 1986.

PMID- 1365078
TI  - Siberia-Canada: joint research on circumpolar health.

PMID- 1365079
TI  - The special premedical studies program--review of ten years of experience.

PMID- 1365081
TI  - Footprints across the snow--learning from Arctic medical history.

PMID- 1365080
TI  - Community development: how can education and training have an impact?

PMID- 1365082
TI  - Joint initiative on health science programs for Native students.

PMID- 1365083
TI  - Providing baccalaureate nursing education to remote populations via
      telecommunications: problems and solutions.

PMID- 1365084
TI  - A northern Bachelor of Nursing Program: one solution to problems in health care
      provision.

PMID- 1365085
TI  - Training/education of local people for posts in the health service-
      neocolonialism?

PMID- 1365086
TI  - Community health representatives working in Labrador Inuit communities.

PMID- 1365087
TI  - The evolution of a village-based health education project.

PMID- 1365088
TI  - The role of the community health aide in rural Alaska.

PMID- 1365089
TI  - Three perspectives on community health aides: surveys of health aides, consumers
      and providers in western Alaska.

PMID- 1365090
TI  - Community Health Aide Program: health care for rural Alaska Natives by rural
      Alaska Natives.

PMID- 1365091
TI  - The health status of communities employing para-professional indigenous community
      health workers as the primary health care provider.

PMID- 1365092
TI  - Movement toward professional excellence--Medical Services Branch Indian Health.

PMID- 1365093
TI  - Health care in crisis: understanding nursing turnover in northern Canada (1).
AB  - For decades nurses have provided 24 hour comprehensive health care in isolated
      communities of Canada. As the only health care personnel in most communities of
      the north, nurses must meet all health care needs ranging from veterinary
      assistance to health education, emergency care to mental health counselling. This
      paper will focus on the structural and psychosocial factors affecting isolated
      post workers. Considering the intense nature of professional responsibility in
      these isolated settings, it is not surprising that there is frequent turnover of
      nurses. The constant change in staff results in poor community and staff morale,
      limited success of programs and increased expenditures for government due to the
      high costs of additional relief staff, travel, and orientation. Utilizing a
      mailed survey (N = 55) and on-site interviews (N = 17) collected in two regions
      of northern Canada, this paper will outline key issues which produce nursing
      dissatisfaction and ultimately decrease the effectiveness of health care
      programs. The paper will conclude with suggestions to increase nursing
      satisfaction and ultimately improve the provision of health care in northern
      areas. Native health care is in crisis. Health status indicators such as infant
      mortality and life expectancy lag far behind national statistics. Death due to
      accidents and violence are almost six times the Canadian rate. Incidence of
      suicide is three times the national statistics (1-6). The rate of nursing staff
      turnover in northern communities is high, and most nurses stay less than 2 years
      in the north (7,8). Native health demands are increasing and it is becoming more
      difficult for find nurses to provide health care service.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1365095
TI  - Research on Indian reserves--an Indian perspective.

PMID- 1365096
TI  - The Health Studies Program; an example of a strategic plan for health research.

PMID- 1365097
TI  - A survey of attitudes of health care personnel in northern Manitoba and the
      Keewatin District towards emergency evacuation services.

PMID- 1365098
TI  - Impact of a solo physician on aspects of health care in a remote Yukon community.

PMID- 1365099
TI  - Medicine and the military in the Canadian Eastern Arctic.

PMID- 1365100
TI  - Physician recruitment by the J.A. Hildes Northern Medical Unit to northern
      Canada: 1970-1990.

PMID- 1365101
TI  - Key note address. Circumpolar Health 90.

PMID- 1365102
TI  - Barriers to health careers in British Columbia: problems and solutions.

PMID- 1365103
TI  - Crossroads in health care: the delivery of two in-service training programs.

PMID- 1365104
TI  - The Orem's conceptual framework as a self determinant for the nursing profession.

PMID- 1365105
TI  - Guidelines for registered nurses practising primary health care in northern
      Saskatchewan.

PMID- 1365106
TI  - Social and economic progress of the north and health of northern Native
      population in the USSR.

PMID- 1365107
TI  - Consultations with Anishinaabe (Ojibway) healers in a Manitoba community.

PMID- 1365108
TI  - Developing an integrated traditional/clinical health system in the Yukon.
AB  - The introductory steps have been taken in Yukon. Elders have met and voiced their
      concerns and initial contacts have been made with government officials, medical
      and legal consultants. A proposal is now being developed to obtain funding to
      design a suitable model for an integrated Yukon Indian/clinical health care
      system. One of the next steps, following on the advice of the Elders, should be
      for communities to establish their own projects to record the plants and
      practices used, with the assistance of their Elders. The communities should also
      identify people who use traditional practices who are willing to come forward.
      They could then come together with the Elders to discuss their concerns. Beyond
      that, representatives from the traditional system will need to meet with
      representatives of the mainstream system, to discuss areas of co-operation. Once
      the "content" has been identified, the model for integrating the two health
      systems can be addressed. This will necessitate further meetings of Yukon
      Territorial Government officials, legal advisors, medical advisors, and Yukon
      First Nations representatives. The proposal currently being developed will build
      on the initial steps which have been taken. The Yukon Territorial Government has
      indicated a willingness to look at ways of including traditional health care
      practices for patients who wish to use them. The receptivity of government and
      Yukon medical profession and the expressed concerns of the Elders indicate that
      now is the time to proceed.

PMID- 1365109
TI  - Alternative programs to long-term institutional care for Alaska's elderly.

PMID- 1365110
TI  - Toullmos, an old healing method of the Skoltsami.

PMID- 1365111
TI  - Understanding Native communities: cross cultural guidelines for health
      professionals.

PMID- 1365112
TI  - Ways of talking about illness in a Manitoba Anishinaabe (Ojibway) community.

PMID- 1365113
TI  - "Being alive well": the praxis of Cree health.

PMID- 1365114
TI  - The role of the interpreter in the provision of specialized medical care.

PMID- 1365115
TI  - Towards the design of culturally appropriate health care facilities.

PMID- 1365116
TI  - Using Native language in general practice.

PMID- 1365117
TI  - Medico-social characteristics of health of communities formation in the north of
      Siberia.

PMID- 1365118
TI  - Social and ecological facts of health of the Native population in Chukotka.

PMID- 1365119
TI  - Mental health problems and services in Greenland.

PMID- 1365120
TI  - The development and evolution of mental health services in the Sioux Lookout zone
      over a nineteen year period.

PMID- 1365121
TI  - The continuum of mental health services available to Indians and Inuit living in
      the Alberta Region.

PMID- 1365122
TI  - Developing community mental health services for indigenous people of northern
      Ontario.
AB  - Inadequacies of three common models of mental health service delivery have been
      presented but each of these can contribute to an adequate system if the approach
      aims at the totality of mental health care. The key to service delivery and the
      provision of services in the local community by adequately trained and supervised
      mental health workers familiar with the culture and language and who are involved
      with other community workers in an inter-agency process. A major and the most
      important part of the work occurs in this level. This front line work must have
      the back-up and support of the system which has three roots. The clinical root is
      that of a support team of professionals, the local nursing station, hospital and
      the tertiary institutions. The second root is in training and education by
      recognized courses and other resources and the third in an adequate
      administration in which the indigenous population has been put in control.

PMID- 1365123
TI  - Challenge of home care in remote communities.

PMID- 1365124
TI  - Alcohol-related mortality in Finnish Lapland.

PMID- 1365125
TI  - Addictive behaviour in conditions of the north.

PMID- 1365126
TI  - Mortality related to alcohol use among the status Indian population of
      Saskatchewan.

PMID- 1365127
TI  - A practical guide to implementing a mobile community treatment process for
      alcohol and drug abuse based on experiences in three small isolated non-treaty
      settlements.

PMID- 1365128
TI  - Community crisis intervention in suicide epidemics.
AB  - The characteristics of "epidemic" suicides in native communities are discussed.
      It is hypothesized that the suicides are but one of many indicators of general
      community disorganization and problems. It is felt that concentration on the
      suicide problem although necessary, may detract from efforts at remedying the
      basic problems. Three communities are used to illustrate their "dynamics" and
      some principles of crisis intervention in such situations are presented.

PMID- 1365129
TI  - Seasonal depression and sleep disturbances in Alaska and Siberia: a pilot study.

PMID- 1365130
TI  - New perspectives on mental health problems in Inuit women.

PMID- 1365131
TI  - Psychiatric service delivery in the eastern Canadian Arctic.

PMID- 1365132
TI  - Community-based suicide prevention programs in rural Alaska: self determination
      as a new approach.

PMID- 1365133
TI  - Towards a new mental health delivery system for Yukon Natives and an exploration
      of masks use for building self esteem.

PMID- 1365134
TI  - Reasons for psychiatric referral in an Inuit population.

PMID- 1365135
TI  - Suicide among Inuit youth in Greenland 1977-86.

PMID- 1365136
TI  - The prevalence of disability in the Baffin: a model for the delivery of community
      based rehabilitation.

PMID- 1365137
TI  - Traditional medicine and mental health care.

PMID- 1365138
TI  - The concepts of health of young Inuit adolescents.

PMID- 1365139
TI  - Health attitudes and behaviours of Native Alaskans.
AB  - Health attitudes and behaviours were determined for residents of Western Alaska
      in a survey administered during the winter of 1988-89. One third of the villages
      in this region were randomly selected for inclusion in he study and one in three
      households in these villages were randomly selected to be interviewed. Bilingual
      interviewers successfully completed questionnaires for 477 households (77%). The
      vast majority of the sample population believed that a balanced diet, weight
      control, regular physical exercise, stress avoidance, regular medical attention
      and cessation of smoking and excessive drinking were important to health.
      Nevertheless 41% of respondents did not deny smoking, and 50% of these did not
      believe smoking cessation was important for health. Similarly, 34% of the
      population did not deny heavy drinking, and 38% of them did not think it was
      important to stop. When those who did not deny smoking were asked if they had
      tried to stop, 36% said they did not try. Of those who did not deny drinking
      heavily, 26% did not try to stop. Western Alaska has high rates of alcohol
      related health problems and growing rates of tobacco-related diseases. The
      attitudes and behaviours with respect to alcohol and tobacco use exhibited in
      this study suggest a great need for health education and promotion activities
      directed at these habits.

PMID- 1365140
TI  - The study of addictive behaviour in Siberia: implications for research in
      circumpolar nations.

PMID- 1365141
TI  - Cultural and psychological perspectives on moxibustion among the Skolt Sami under
      conditions of cultural change.

PMID- 1365142
TI  - Cerebral hemispheric asymmetry of function in seasonal affective disorder and
      light treatment.

PMID- 1365143
TI  - The effects of phototherapy (PT) on diurnal rhythms of physiological parameters
      and melatonin excretion in subjects with seasonal affective disorder (SAD).

PMID- 1365144
TI  - Phototherapy for seasonal affective disorder (SAD) in Siberia.

PMID- 1365145
TI  - Infectious diseases in Lapland in the years 1987-1989.

PMID- 1365147
TI  - Urban native health care in Canada: the relevance of socio-economic status.

PMID- 1365146
TI  - An unusual epidemic of isoniazid resistant tuberculosis in a western Alaska
      Eskimo village-portents for the future?

PMID- 1365148
TI  - The launch of an infant Haemophilus influenzae type B immunization programme in
      Iceland.

PMID- 1365150
TI  - Toxigenic diphtheria in two isolated northern communities.

PMID- 1365149
TI  - Antibody to H. influenzae type B capsular polysaccharide in maternal and cord
      sera from Inuit, Native Indian and Caucasian subjects in the Northwest
      Territories and Manitoba.

PMID- 1365151
TI  - Sexually transmitted diseases in Greenland: a three-year review.

PMID- 1365153
TI  - HIV infection and AIDS in Alaska: epidemiology and prevention strategies.

PMID- 1365152
TI  - The use of reported sexually transmitted disease data as an evaluative tool for
      HIV prevention efforts in the Northwest Territories.

PMID- 1365154
TI  - An outbreak of congenital toxoplasmosis in northern Quebec.

PMID- 1365155
TI  - Establishing the Joint National Committee on Aboriginal AIDS Education and
      Prevention.

PMID- 1365156
TI  - Viral hepatitis--immunoprophylaxis.

PMID- 1365157
TI  - Medico-social aspects of Chucotka Natives health improvement: materials and
      spiritual problems.

PMID- 1365158
TI  - Relationship between tuberculin reactivity and hepatitis B virus infection in the
      Northwest Territories.
AB  - Of 370 NWT Inuit or Dene who were HBsAg-positive, only 31 had HBeAg. Persons who
      were PPD negative were 6.2 times more likely to be HBeAg-positive than those who
      were PPD positive, but this inverse association applied only to those 30 years of
      age. We further analyzed a group of 3,378 Inuit whose status was known for HBV
      serologic markers and PPD reactivity. Overall, a significantly greater proportion
      (76.2%) of HBsAg positives were PPD reactive in comparison to those positive for
      anti-HBs (67.2%) or who had no HBV markers (43.2%). For persons 30 years of age
      who were positive for HBsAg or anti-HBs there was no significant difference
      between the proportions with PPD reactivity but a significantly smaller
      proportion of PPD reactivity was found in the no marker group. Among persons 30
      years of age, the proportions of those who were PPD reactive were statistically
      equivalent across all three HBV marker groups. We conclude that patterns of HBV
      infection in NWT are random with respect to tuberculin reactivity resulting from
      either exposure to M. tuberculosis or administration of BCG vaccine.

PMID- 1365159
TI  - Public knowledge about hepatitis B related issues in a high risk population.

PMID- 1365161
TI  - AIDS: the global challenge for nursing.

PMID- 1365160
TI  - A case of insect borne tularemia above the tree line.
AB  - A case of insect borne transmission of ulceroglandular tularemia in Canada above
      the tree line is presented. It seems likely from the available entomological data
      that a mosquito was the vector in this case. Mosquito vectors may be important in
      inducing the high seroprevalence of antibodies to F. tularensis above the
      treeline. This case is presented to make clinicians aware of the possibility of
      tularemia in cases of insect borne ulceroglandular disease in the arctic and, the
      necessity of measuring tularemia agglutinins in these patients. It should be
      noted that isolation of this organism poses a risk to laboratory personnel, and
      therefore should only be attempted in a reference laboratory. Therefore the
      diagnosis is based upon the finding, in the appropriate clinical context, of a
      four-fold rise in the tularemia agglutinins, or a single convalescent titre of
      1:160 or greater.

PMID- 1365162
TI  - A community response to an outbreak of pertussis in Yukon.

PMID- 1365163
TI  - Determinants of tuberculin sensitivity in a child population covered by mass BCG
      vaccination.

PMID- 1365164
TI  - Perceived and observed health status of Inuit receiving social assistance.

PMID- 1365165
TI  - Low relative risk of epiglottitis in Manitoba Indians.

PMID- 1365166
TI  - An aetiologic view on cardiovascular diseases in the Arctic.

PMID- 1365167
TI  - Atherosclerosis in Greenland: an ultrasonographic investigation.

PMID- 1365168
TI  - The Svalbard Study: risk of coronary heart disease at 78 degrees north.

PMID- 1365170
TI  - Risk factors and chronic noncommunicable diseases in Native residents and
      newcoming population of Chukotka.

PMID- 1365169
TI  - Coronary atherosclerosis and ischemic heart disease in aboriginal and newcomer
      male populations of Yakutia.

PMID- 1365171
TI  - Prevalence and correlates of hypertension in a subarctic Indian population.

PMID- 1365172
TI  - Alcohol consumption in western Siberia connection with serum blood lipids,
      ischemic heart disease and arterial hypertension.

PMID- 1365173
TI  - Diabetes, glucose tolerance and some risk-factors of diabetes mellitus in Natives
      and newcomers of Chukotka.

PMID- 1365175
TI  - A hereditary mitochondrial myopathy with low succinate dehydrogenase activity in
      northern Sweden.

PMID- 1365174
TI  - The effectiveness of a team approach to diabetes program management in interior
      Alaska.

PMID- 1365176
TI  - Indian health and community development: notes for an address.

PMID- 1365177
TI  - Influence of genetic and demographic factors on etiology and pathogenesis of
      chronic disease in north Siberian aborigines.

PMID- 1365178
TI  - Prevalence of diabetes mellitus in pregnancy among Yup'ik Eskimos and Alaska
      Coastal Indians, 1987-1988.

PMID- 1365179
TI  - Alcohol consumption and risk-factors for ischemic heart disease in Chuckchi
      inhabitants: clinical, biological and population studies.
AB  - Clinical, biochemical and epidemiological research has shown variations of serum
      enzymatic constellations (relatively high level of GGT in Chuckchi natives
      compared to nonnative newcomers). This difference leads to different unspecific
      body resistance to exogenous factors, particularly to histamine-liberators. The
      GGT system has also been linked to alcohol-induced clinical IHD. Based on these
      findings patients will be screened for GGT activity, which may serve as a marker
      for population phenotypes representative of high-risk groups. This deficiency in
      GGT may indicate a high risk for alcohol-related heart disease.

PMID- 1365180
TI  - IHD in male population of Novosibirsk and Chukotka.
AB  - 1. Syndrome of angina pectoris of effort is the most typical manifestation of IHD
      in native and newcoming population of the coastal part of Chukotka. 2. Ischemic
      ECG changes are less specific in relationship to IHD for Chukotka native
      population than in Chukotka newcoming and Novosibirsk populations.

PMID- 1365181
TI  - IHD in Chukotka residents: concentration of thyrotropin, thyroxin,
      triiodothyronine in blood serum.

PMID- 1365182
TI  - Prognostic significance of static endurance (Hand Grip Test) in northern arterial
      hypertension.

PMID- 1365183
TI  - Diabetes mellitus in the Native population of British Columbia, Canada.

PMID- 1365185
TI  - Implementing primary health care through community control: the experience of
      Swampy Cree Tribal Council.

PMID- 1365184
TI  - Echocardiographic assessment of cardiac abnormalities and their relationship to
      exercise blood pressure in two Icelandic populations.

PMID- 1365186
TI  - Circumpolar cancer--international cooperation in prevention and control programs.

PMID- 1365187
TI  - Cancer patterns in the Inuit population of Canada 1970-1984.
AB  - 1. Rates for lung cancer in Canadian Inuit are high and increasing for both men
      and women; in fact they are the highest reported rates for lung cancer among any
      Inuit population. 2. Cervical cancer in Canadian Inuit are high but rates appear
      to be stable, unlike the rapidly increasing trend reported in both Alaska and
      Greenland. 3. Rates for traditional Inuit cancers such as those of the
      nasopharynx and salivary gland do not appear to be declining in Canadian Inuit.
      4. Rates for colorectal cancer in Canadian Inuit are similar to those expected
      for the Canadian population as a whole and do not appear to be increasing. 5.
      Finally, cancers traditionally reported to be rare in Inuit are still rare in the
      Canadian Inuit population; these include breast, prostate, bladder, and
      endometrial cancer. Cancer is a disease which can be controlled through
      prevention, early detection or treatment. The following future directions arising
      from this work reflect this paradigm. First, the Inuit cancer registry developed
      for this analysis will be used as a base for further research into environmental
      and genetic factors influencing cancer rates in the Inuit. Second, given that at
      least 40% of cancers in Canadian Inuit are cancers of the lung and cervix, health
      promotion programs should be developed to encourage tobacco-free environments to
      halt the epidemic of lung cancer, and also to make available Pap smear programs
      for early detection of cervical cancer. Third, health care services and programs,
      including diagnosis and treatment, should be culturally accessible to the Inuit
      population (6).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1365188
TI  - Cancer incidence and survival of Saskatchewan northerners and registered Indians,
      1967-1986.

PMID- 1365190
TI  - Fighting cancer in Greenland: the Danish Cancer Society strategies.

PMID- 1365189
TI  - Lung, breast and cervical cancer incidence and survival in Saskatchewan
      northerners and registered Indians (1967-86).

PMID- 1365191
TI  - Cancer registration and trends in cancer incidence in the Northwest Territories.

PMID- 1365192
TI  - Screening for cancer in remotely populated regions--lessons from mammography and
      breast cancer.

PMID- 1365193
TI  - Hereditary site-specific colon cancer in a Canadian kindred.
AB  - In summary, we have presented a large Canadian kindred exhibiting hereditary
      large bowel cancer, without polyposis coli, transmitted in an autosomal dominant
      fashion (Hereditary Site-Specific Colon Cancer). This series serves to emphasize
      the heritable nature of this and other malignant conditions and the importance of
      so fundamental a concept as the taking of a complete family history in the
      identification and management of these conditions. Looking to the future, the
      reduction of morbidity and mortality from Hereditary Site-Specific Colon Cancer
      lies in the education of the family and genetic counselling, both commencing in
      the mid teens the education of physicians and surgeons in the very considerable
      risk of malignancy in this condition the surveillance of asymptomatic family
      members including such measures as stool testing for occult blood six monthly
      augmented by air contrast barium enema and/or colonoscopy at two yearly
      intervals, commencing at age 25 the creation of national and international
      registries the identification of reliable biomarkers. We are indeed fortunate to
      live in a age when technology holds promise for the identification of the
      oncogenes operative in this and other heritable malignancies. This is the subject
      of ongoing collaboration between us and our molecular biology colleagues at
      Memorial University in St. John's and exemplifies, I believe, the very best in
      the cooperative spirit which may exist between a community hospital and a larger
      teaching centre.

PMID- 1365194
TI  - Stomach cancer among the aboriginal population of the Soviet Far East: an
      epidemiological study.

PMID- 1365195
TI  - The William Charles Health Centre of Montreal Lake Band: a case study of
      transfer.

PMID- 1365196
TI  - A comparison of cancer in Greenland and Denmark. A study based on routinely
      collected incidence data 1973-1985, using the Danish population as baseline.

PMID- 1365197
TI  - Alaskan and Siberian studies on alcoholic behavior and genetic predisposition.

PMID- 1365198
TI  - Stresses encountered in the trans-polar ski-trek.

PMID- 1365199
TI  - Polar bridge: the union of Soviet and Canadian science, culture and determination
      across the Arctic Ocean.

PMID- 1365200
TI  - Effect of a 91-day polar ski expedition on cold acclimatization.

PMID- 1365201
TI  - Medical observations of members of the Soviet/Canadian 1988 Polar Bridge
      Expedition.

PMID- 1365202
TI  - Physiological evaluation of the Soviet and Canadian trekkers prior to and
      following the 1988 Polar Bridge Expedition.

PMID- 1365203
TI  - Structural and functional features of erythrocyte membranes in members of a
      transarctic skitrek.

PMID- 1365205
TI  - Regional health boards and the democratization of health care in the Northwest
      Territories.

PMID- 1365204
TI  - Humans on ice: a review of research on those living in Antarctica since IGY 1957
      58.

PMID- 1365206
TI  - The Australian National Antarctic Research Expeditions Health Register: three
      years of operation.

PMID- 1365207
TI  - Anterior chamber depth in Arctic and tropical populations.

PMID- 1365208
TI  - Prevalence of cardiovascular risk factors in two separate but genetically
      comparable populations.

PMID- 1365209
TI  - The fatty acid profile in plasma phospholipids of two separate but genetically
      comparable populations.

PMID- 1365210
TI  - Prevalence of hypertension in two separate but genetically comparable adult
      populations.

PMID- 1365211
TI  - Estimation of the relative contribution of genetic and environmental factors to
      population variability of blood serum lipid and arterial blood pressure in the
      Native population of Chukotka.

PMID- 1365212
TI  - Physiological responses to cold stress.

PMID- 1365213
TI  - Cold physiology.

PMID- 1365214
TI  - Reaction of patients with effort angina to cold exposure during exercise.
AB  - An attempt has been made to characterize so-called "responders" to cold among
      patients with effort angina. Forty-nine such patients, unselected with regard to
      their history of reactions to cold, who showed ST depressions during and after
      exercise, were examined. They worked on a bicycle ergometer close to their
      maximum capacity, Wmax, at room temperature (about 23 degrees C) and in a cold
      room (-15 degrees C). ECG was recorded and a rating scale was used to estimate
      the perceived exertion during exercise (RPE). The presence of angina pectoris
      during exercise and its duration after exercise was recorded by an EA score. An
      EA/W index was used to estimate the severity of the effort angina. In the whole
      group, the mean Wmax decreased and the mean ST depressions, RPE, and EA/W index
      (but not EA score) increased on exposure to cold. The changes in these variables
      due to exposure to cold were all associated (but not the EA score). Criteria
      requiring a decrease in Wmax or increase in ST depression, RPE or EA/W index on
      cold exposure identified 53 to 63 percent of the patients. By combining the
      criteria, the number of patients, who were identified, decreased. If all the
      criteria were applied, about 30 percent of the patients were identified as
      "responders" to cold and they showed the most marked responses. Thus several
      exercise ECG test parameters may be used to reliably define "responders" to cold
      exposure. This may enhance future studies of the response reaction.

PMID- 1365215
TI  - Adaptation and circadian rhythmicity of lymphoid system.

PMID- 1365216
TI  - Pathophysiology of thermoregulation in patients with poikilothermia.
AB  - To investigate the thermoregulatory mechanisms underlying poikilothermia in man,
      we have studied 4 female patients (age 28-37 yr) with poikilothermia, most
      probably of hypothalamic origin, as well as 4 female volunteers of similar age.
      In a climatic chamber the participants were subjected to cold stress (16.5
      degrees C) and subsequent heat exposure (40 degrees C). In the volunteers cold
      stress did not influence the rectal temperature; cooling induced a marked
      shivering response and an immediate peripheral vasoconstriction. Subsequent heat
      challenge induced a slight rise in the rectal temperature (from 36.3 +/- 0.2 to
      37.0 +/- 0.3 degrees C) and a marked sweat secretion in all control subjects. All
      patients were hypothermic at the start of the experiment. Cooling induced a
      decrease in the rectal temperature of 0.3-0.9 degrees C. Three patients showed
      neither peripheral vasoconstriction nor a shivering response to cold stress. In
      contradistinction to the control subjects, in all patients an afterdrop of the
      rectal temperature of 0.3-0.5 degrees C was observed once heating of the
      environment had started; thereafter a progressive rise in core temperature
      occurred up to 38.5 (38.0) degrees C. In none of the patients sweat secretion was
      clinically visible. These results reveal that in these patients with
      poikilothermia the disorder of thermoregulation is accompanied by inadequate
      cutaneous vasomotor adjustment and disturbed sweat response and likely reduced
      metabolic response to cold stress.

PMID- 1365217
TI  - Thermoregulation in man during cold adaptation.
AB  - Permanent residence in a cold environment affects the thermoregulatory system and
      other related functions (Table 5). These changes are adaptive because they
      decrease the stress action of cold, maintain the energy cost of temperature
      homeostasis and make it possible to receive additional heat during muscular work
      in cold without drawing on such heat production sources as shivering.

PMID- 1365218
TI  - Specificities of adaptation in aboriginal and newcomer populations of Alaska and
      Chukotka in the process of intensive physiological loads.

PMID- 1365219
TI  - Cognitive and physiological feedback on cold pain tolerance.
AB  - Results supported the relevancy of cognitive information effects on pain
      tolerance, in that subjects who were given a rational and accurate explanation of
      what to expect showed greater tolerance than those who received irrelevant
      information. Accurate monitoring of hand temperature did not seem necessarily
      advantagous as an influence on pain tolerance. It appears merely watching a
      monitor, regardless of the specific contents of the screen, resulted in longer
      hand immersion times when compared to no monitor. The monitors seem to serve as
      distractors and specificity of physiological information was not particularly
      useful. However, neither information nor physiological monitoring emerged as the
      primary influence on pain tolerance in this study. Instead, the strongest
      predictors found were motivation and self-efficacy. The subject's own self
      prediction of anticipated performance with cold induced pain was closely
      consistent with actual performance. Although these results alone may not
      generalize to extended field situations, this study does reinforce the general
      findings of previous research: namely Bandura's (10) evidence on self-efficacy.
      While it is obvious cold temperatures have measurable physiological consequences,
      the experience of pain is also psychologically mediated. Pain associated with
      cold injury and frostbite in hospital studies show personality correlates are
      significantly related to the frequency, severity and tragedy of subsequent
      results (15). A replication of this study will include male subjects even though
      it is anticipated that findings will be consistent, with perhaps longer immersion
      times. Future research may want to develop training strategies aimed at teaching
      self-efficacy and realistic expectations of potential consequences in cold
      environments rather than scare tactics regarding physiological and psychological
      cold pain tolerance.

PMID- 1365220
TI  - Indigenous control of health services.

PMID- 1365221
TI  - The 1988 Polar Bridge Expedition: effects of the three-month trans-polar ski-trek
      on aerobic fitness and skiing economy.

PMID- 1365222
TI  - The role of hereditary factors in phenotypic variability of hormone levels in a
      population genetically adapted to the circumpolar environment.
AB  - The variability of plasma cortisol, T3, T4, TSH, and estradiol levels was studied
      in the North Khanty population genetically adapted to the extreme conditions of
      the North. Negative linear correlations of T3 and T4 levels with age were
      obtained. Cortisol, estradiol, and T3 levels showed nonlinear age dependency. T4
      concentrations were significantly lower in August than February and November. The
      highest heritability estimate was shown for estradiol levels (44%). The
      relationships between genetic markers and hormone concentrations were studied.

PMID- 1365223
TI  - Biochemical changes in the blood of participants of the Soviet-Canadian
      transarctic ski-journey.

PMID- 1365224
TI  - Unmet needs of children in Canada's north: nutrition, injury prevention and
      problems of adolescents.

PMID- 1365225
TI  - Infant and child mortality in Greenland is too high.

PMID- 1365226
TI  - Complex evaluation of Native and alien population children health status in
      Pryamurye region from ecological and donozological points of view.

PMID- 1365227
TI  - National database on breastfeeding among Indian and Inuit women: Canada 1988.

PMID- 1365228
TI  - Saliva cotinine concentrations in young children in rural Alaska.

PMID- 1365229
TI  - A need for comprehensive action to enhance Manitoba Indian children's academic
      achievement.

PMID- 1365230
TI  - Obstetric policy for the Keewatin Region, N.W.T.: results of the childbirth
      experience survey.

PMID- 1365231
TI  - The delivery of prenatal care to women from the Keewatin: 1979-85.

PMID- 1365232
TI  - Breastfeeding in the Mohawk community of Kahnawake: revisited and redefined.

PMID- 1365233
TI  - Family violence in the north: what do we know and where do we go from here?
AB  - This paper has attempted to outline questions which should and should not be part
      of a Northern research agenda. There is, in my view, a large need for continued
      applied and evaluative research which will make a direct contribution to ending
      violence against women and children. Both researchers and funding bodies have a
      responsibility to ensure that limited resources are used wisely and, in
      particular, that the funding of any research project be contingent upon a clear
      demonstration of the direct and immediate relevance of the findings to the
      development and improvement of services.

PMID- 1365234
TI  - Canadian First Nation Control of Health: a successful case study.

PMID- 1365235
TI  - Socioeconomic and environmental characteristics of women of domestic violence in
      Alaska.

PMID- 1365236
TI  - Maternal health and obstetrical services: measuring health status and the quality
      of care in remote areas.

PMID- 1365237
TI  - Evacuation for childbirth in the Baffin Region, N.W.T.: factors associated with
      the length of family separation.

PMID- 1365238
TI  - Changes in blood mercury and lead levels in pregnant women in Greenland 1983
      1988.

PMID- 1365239
TI  - Pedagogical basis for mass defects in vision in the young generation of the
      Native peoples--perspectives to solve the problem.

PMID- 1365240
TI  - Yupik translation of the Hearing Handicap Inventory for the Elderly.

PMID- 1365241
TI  - An overview of twenty years of observation concerning etiology, prevalence, and
      evolution of otitis media and hearing loss among the Inuit in the eastern
      Canadian Arctic.

PMID- 1365242
TI  - Causes of chronic suppurative otitis media (CSOM) in Australian aboriginal
      infants and children.

PMID- 1365243
TI  - Epidemiology of otitis media in aboriginal children in Australia.

PMID- 1365244
TI  - The search for the etiology of otitis media: results obtained with an application
      of the system theory.

PMID- 1365245
TI  - Indigenous peoples plenary session address.

PMID- 1365246
TI  - Delivery of audiologic service and prevalence of hearing loss in the western
      Canadian Arctic.

PMID- 1365247
TI  - Obstacles, challenges, and solutions: evolution in audiological service delivery
      to the hearing-impaired Inuit of northern Quebec.

PMID- 1365248
TI  - Audiological rehabilitation of Greenlandic patients with hearing loss due to
      otitis media.

PMID- 1365249
TI  - Developmental and educational effects of conductive hearing loss among Australian
      aboriginal children and implications for educational management.

PMID- 1365250
TI  - A study on cost effectiveness of audiology services Baffin Region, N.W.T.

PMID- 1365251
TI  - Electrocochleography: a new dimension in otology & audiology.

PMID- 1365252
TI  - Otitis media and the patterns of child morbidity in Kuujjuarapik.

PMID- 1365253
TI  - Chronic purulent otitis media: the prevailing pathology form among northern
      nationalities.

PMID- 1365254
TI  - Prevalence of hearing loss in northern Quebec: a medical and statistical
      challenge.

PMID- 1365255
TI  - Provision of dental care to the Arctic and subarctic regions of Canada: the
      University of Toronto's role.

PMID- 1365256
TI  - An oral health survey of Head Start children in Alaska.

PMID- 1365257
TI  - The Alaska Area Native Health Service: improving the health status of the native
      people of Alaska.

PMID- 1365258
TI  - The effect of non-insured health benefits on dental treatment provided in four
      coastal Labrador communities by salaried dentists.

PMID- 1365259
TI  - The oral health status of the Inuit people of the North Slope of Alaska.

PMID- 1365260
TI  - A collaborative approach to developing dental health resources for northern
      communities.

PMID- 1365261
TI  - Dental therapists and the delivery of dental: care in Canada's Northwest
      Territories.

PMID- 1365262
TI  - Frustrations in delivering a dental service to the north coast of Labrador.
AB  - The delivery of a dental service to 4,000 people by 2-3 dentists, appears
      straight forward, in theory. It proves to be a different story in reality. Having
      prior knowledge of these problems, may be of help to dentists who wish to work
      here. One must experience the situation for oneself, however. There are certainly
      a "more than normal" amount of problems to confront on a daily basis.
      Accommodation and travel arrangements, seem to be the most pressing issues which
      need improvement. The usual work span of a dentist is between one and three
      years. The amount of work done by each dentist can vary on a daily basis. Native
      traditions can be such that, patients do not show up at the dental clinic until
      too late. Violence, suicides, and alcohol or solvent and drug abuse, as is being
      seen today, can "burn out" any health worker. Equipment needs to be upgraded in
      some of the Stations, like Hopedale and Davis Inlet. Salaries need revising.

PMID- 1365263
TI  - A study to establish parameters for the use of pit and fissure sealants in a
      group of Indian children with high caries rates.

PMID- 1365264
TI  - Perceived problems of oral health in elderly people living at home.

PMID- 1365265
TI  - Experiences with dental therapists from the Arctic to Africa.

PMID- 1365266
TI  - Dental caries indices and treatment levels in a young Canadian Inuit population.

PMID- 1365267
TI  - A descriptive study of early caries and oral health habits of Inuit pre
      schoolers: preliminary results.
AB  - Despite reports describing the high incidence of baby bottle tooth decay (BBTD)
      in North American native populations, very little is known about the factors
      influencing dental health at such an early age. Furthermore, true prevalence
      figures are usually difficult to obtain because few studies have attempted to
      survey the whole population. The purpose of this project is to determine the true
      prevalence of nursing caries in the Kativik region and describe oral health
      determinants in relation to the dental status of these children. At this time,
      244 children aged two to five years have been surveyed. The results indicate that
      baby bottle tooth decay occur in 72.2% of this young population.

PMID- 1365268
TI  - A comparison of frequency and duration of dental visits and treatments for two
      northern Labrador communities.

PMID- 1365270
TI  - What is social environment and how does it influence health in Greenland?

PMID- 1365269
TI  - Evaluation of periodontal therapy using the Community Periodontal Index of
      Treatment Needs (CPITN).

PMID- 1365271
TI  - Determinants of exposure to methylmercury among the James Bay Cree, 1987-89.

PMID- 1365272
TI  - PCB incineration in Labrador.

PMID- 1365273
TI  - Bush food contamination and public health policy.

PMID- 1365274
TI  - Organization and perspectives of development of mobile health care in Chukotka.

PMID- 1365275
TI  - Status of water supply and waste disposal services in rural Alaska.

PMID- 1365276
TI  - Prospects of the noospheric development of the circumpolar territories.

PMID- 1365277
TI  - Out patient medical service independent of a hospital: a model for the health
      care of indigenous peoples.

PMID- 1365278
TI  - Human exposure as a monitor of environmental contamination: its possibilities and
      limitations as illustrated by the case of methylmercury in northern Quebec.

PMID- 1365279
TI  - Occupational health in Alaska: problems and potential.

PMID- 1365280
TI  - A comparison of the patterns of illness and injury occurring on offshore
      structures in the northern North Sea and the stations of the British Antarctic
      Survey.

PMID- 1365281
TI  - Traumatic occupational fatalities: how Alaska differs from the U.S. National
      Statistics. Implications for circumpolar health.

PMID- 1365282
TI  - Nutrition of the Inuit: a brief overview.
AB  - Changing food preferences and health beliefs are resulting in a decline in use of
      traditional Inuit foods and an increase in use marketed foods. These changes are
      associated by many researchers with a variety of health concerns that currently
      are increasing among Inuit populations. Recent food composition studies have
      facilitated evaluation of dietary intakes of nutrients and organochlorine
      contaminants. In one Baffin Inuit community, traditional Inuit food species were
      found to still be a major component of women's diets, and to make a significantly
      greater contribution than marketed foods for certain nutrients; however on the
      annual average marketed foods contributed greater amounts of total dietary
      energy, fat and calcium. Vitamin A and calcium were found to be routinely below
      recommended amounts in women's diets. PCBs and toxaphene's were contained in the
      diet in fatty sea mammal tissues; however the average woman's diet, on the annual
      basis, contained less than one-third of the provisional tolerable levels of these
      organochlorine contaminants. The diets of the Inuit, as of all Indigenous People,
      are not comprised solely of the historically traditional foods; however these
      foods are still vitally important as a source of nutrients and cultural
      definition. The presence of industry-derived organochlorine contaminants in Inuit
      food species is yet another demonstration that action is needed on environmental
      protection by local, national and international agencies.

PMID- 1365283
TI  - The importance of a functional communications system in the provision of health
      care in rural Alaska.
AB  - Paraprofessional health care workers in rural Alaska rely on an intact
      communication system for guidance in patient care and as a source of support for
      themselves in performing a difficult job. Though able to function without the
      system when necessary, the telephone reduces the crushing sense of responsibility
      and profound isolation experienced by CHAs as they struggle to meet the health
      care needs of their communities.

PMID- 1365284
TI  - Dietary intake and nutritional status of Canadian Indians: a review.

PMID- 1365285
TI  - Dietary intakes of Alaska Native adults 1987-1988.

PMID- 1365286
TI  - The Svalbard Study: increased body weight at 78 degrees north.

PMID- 1365287
TI  - Nutrient intake among Saami people today compared with an old, traditional Saami
      diet.
AB  - The Saami diet consisted almost entirely of meat and fish in the past and has in
      general changed considerably during the twentieth century. The diet has become
      more like a western society diet with increased intake of carbohydrates, both as
      vegetables and fruits but also as sugar and a decreased intake of meat. These
      changes are confirmed in this dietary survey and the results reveals that the
      Saami diet today contains less protein and more carbohydrates and hence a lower
      phosphate/carbohydrate ratio than in the past. The old traditional diet contained
      high levels of nutrients such as zinc, phosphate, vitamin B12 and selenium due to
      high meat consumption. The todays Saami diet still contains more of these
      nutrients compared with the Swede's diet. The changes in food habits and nutrient
      intake, expressed in this study as nutrient density and nutrient ratios together
      with empirical statements in old documents are important to include in the
      discussion of diet, health and disease.

PMID- 1365288
TI  - Benefit-risk considerations of traditional food use by the Sahtu (Hare)
      Dene/Metis of Fort Good Hope, N.W.T.
AB  - In summary, based on these preliminary data: a) traditional Dene foods make a
      substantial contribution to the adult RNI for protein, iron, and zinc; b) the
      Dene component of the diet is lower in total fat and has a higher P:S ratio than
      does the marketed component; and c) adults consuming a variety of Dene foods at
      the current average level of consumption during high traditional food use periods
      are not at risk of exceeding the provisional tolerable daily intake for PCBs. In
      conclusion, however unattainable "zero-risk" in food is, the fact remains that
      striving towards it is an important goal socially, physiologically, and
      ecologically. Managing risk on both global and individual levels is necessary.

PMID- 1365289
TI  - A preliminary comparison of nutrient intakes of Siberian Chukotka and Alaska
      Natives.

PMID- 1365290
TI  - Economic barriers to optimum nutrition in Native communities in British Columbia.

PMID- 1365291
TI  - Nutrition education for Native treatment centres.
AB  - Based on a needs assessment of native treatment centres and a pilot training
      project, a 10-day nutrition workshop was offered to 49 counsellors and cooks from
      30 native treatment centres from six provinces. Objectives were to: 1) improve
      the understanding of the effect of alcohol on health and nutrition; 2) to improve
      the understanding of the role of nutrition in rehabilitation; 3) to clarify their
      respective roles and 4) to improve skills in menu planning for recovery and
      special diets, food safety procedures and cooking techniques appropriate for
      recovery. Assessment, counselling and treatment were considered in relation to
      native cultural values, meeting basic human needs and counselling theory.
      Participants rated the following at four or five (on a scale of one to five):
      meeting their expectations (98%); improving their understanding of the role of
      nutrition in total well being and recovery (98%); the effect of alcohol on health
      and nutrition (98%); the recovery diet (96%), special diets and planning and
      adapting menus (94%) and food safety (96%); developing skills in nutritional
      assessment (92%) and counselling (89%). Ninety-two percent were interested in
      further training and 94% of participants would recommend this training to others
      in the addiction field.

PMID- 1365292
TI  - Comparison of factors affecting native health in Canada and the United States.

PMID- 1365293
TI  - The preparation of a pamphlet and poster promoting traditional Yukon First
      Nations diet.

PMID- 1365295
TI  - Influence of diet on blood cadmium in Greenlanders.

PMID- 1365294
TI  - Dietary omega 3 fatty acids and gestational hypertension in the Inuit.
AB  - Blood pressure at the end of pregnancy and the incidence of pregnancy-induced
      hypertension were monitored in Inuit communities in the Keewatin region of the
      Northwest Territories. Communities with more fish and sea mammals in their diet
      had a lower blood pressure at the end of pregnancy and a lower incidence of
      gestational hypertension. The lower incidence of gestational hypertension was
      independent of other variables, including pregravida weight and parity. Cord
      blood phospholipid fatty acid analysis confirmed higher levels of eicosapentanoic
      acid, a fatty acid enriched in fish and sea mammals, in infants born to mothers
      from communities with higher fish in their diets.

PMID- 1365296
TI  - Physical activity, smoking and overweight among the Cree of eastern James Bay.

PMID- 1365297
TI  - Nutrient intake of adults aged 15 to 65 years in two northern Ontario
      communities.

PMID- 1365299
TI  - Luttamiut (doctor's people) and "old wives' tales"--their unrecognized value in
      medicine.

PMID- 1365298
TI  - Prevalence of iron-deficiency states among Siberian women.

PMID- 1365300
TI  - Referral of patients from northern Labrador.

PMID- 1365301
TI  - Research and the improvement of remote health care--an Antarctic example.

PMID- 1365302
TI  - No information on a forgotten people: how healthy are Native people in Canada
      when they live off reserve.

PMID- 1365303
TI  - Health and disease in Amazonian tribes: new challenges.

PMID- 1365304
TI  - A revised weight loss program in Manitoba Native communities.
AB  - In summary a culturally relevant weight loss program should consider the factors
      of age, education, economics and community. If these factors are not considered
      then it is the opinion of the author that programs involved with health may not
      succeed on a reserve.

PMID- 1365305
TI  - The health of the Eskimos: an updated selective bibliography.

PMID- 1365306
TI  - Signal transduction pathways in keratinocytes.
AB  - Mammalian cells do not live as isolated organisms, but are instead organized into
      complex, highly specialized tissue organs composed of a homogeneous or a mixed
      cell population. In order to maintain tissue homeostasis in physiological and
      pathophysiological conditions, intercellular communication is an absolute
      requirement. This review will summarize our current knowledge as to how an
      extracellular signal is transduced via a specific receptor to the interior of the
      cell and how this signal will induce special cell functions. Attention will be
      paid to the major signal transduction pathways known to be active in
      keratinocytes, namely the adenylate cyclase, guanylate cyclase, tyrosine kinase,
      and phospholipase C systems. Finally, examples will be given of how interactions
      between these signal transduction pathways can take place and how 'signal cross
      talk' might regulate keratinocyte function.

PMID- 1365307
TI  - Isolation of plasma membranes from keratinocytes: a newly developed method allows
      the sensitive detection of the membrane antigen pattern in normal and psoriatic
      skin.
AB  - Distinct differences of proteins in the plasma membranes have been described in
      psoriatic keratinocytes as compared with normal epidermis. These changes are
      presumably involved in the pathogenesis of psoriasis. To identify and distinguish
      glycosylated proteins of the plasma membranes of keratinocytes, a method for mild
      preparation was developed that avoids the use of degrading or digestive enzymes.
      After cell lysis, three steps of centrifugation were performed, including the use
      of a sucrose step gradient. A fine-vesicular membrane fraction was obtained.
      Using marker enzymes for cell compartments, no contamination of cell nuclei or
      mitochondria and only 0.4% of endoplasmic reticulum was detectable in the final
      membrane fraction. Based on this preparation, disc-polyacrylamide-gel
      electrophoresis, followed by Western blotting, were performed. Staining with five
      different lectins to visualize glycosylated proteins allowed 75 different
      membrane glycoproteins to be distinguished. The patterns of normal, transformed
      (HaCaT), foreskin and psoriatic keratinocytes after cell culture with one passage
      were compared. Up to six proteins per lectin staining were expressed differently
      in psoriatic as compared to normal keratinocytes. Psoriatic cells shared
      similarities with highly proliferative foreskin cells, but not with transformed
      HaCaT cells. Main alterations of glycosylation were detected in the fucose
      content. In conclusion, the method developed for isolation of plasma membranes
      allows selective and sensitive examination of plasma membranes of normal and
      pathological keratinocytes. The glycosylation patterns observed suggest that
      distinct membrane proteins may be involved in the pathogenesis of psoriasis.

PMID- 1365308
TI  - Induction of inflammatory cytokines in murine keratinocytes upon in vivo
      stimulation with contact sensitizers and tolerizing analogues.
AB  - In order to elucidate the role of keratinocytes (KCs) in the induction of contact
      sensitivity, we applied various contact sensitizers [2,4-dinitrofluorobenzene
      (DNFB), urushiol, 3-n-pentadecylcatechol (PDC), 4-ethoxymethylene-2-phenyloxazol
      5-one (oxazolone)] and tolerizing compounds [2,4-dinitrothiocyanobenzene (DNTB),
      5-methyl-3-n-pentadecyl-catechol (5-Me-PDC)] onto the earskin of non-sensitized
      Balb/c mice. In addition, we applied croton oil as a non-sensitizing, but
      stimulatory agent. Cytokine production was demonstrated by Northern blot
      hybridization of the total cellular RNA extracted from epidermal cells depleted
      by Langerhans cells and Thy 1+ dendritic cells using radiolabeled DNA probes
      encoding for the murine cytokines IL-1 alpha, -2, -3, -4, TNF alpha, IFN tau, GM
      CSF and G-CSF. From all cytokines tested, TNF alpha and IL-1 alpha were markedly
      increased upon in vivo stimulation with contact sensitizers and also after
      application of croton oil. Both light and electron microscopic immunostaining
      with a polyclonal and monoclonal antibody demonstrated the presence of TNF alpha
      in the epidermis. This staining was most pronounced in KCs of the suprabasal
      epidermis upon application of contact sensitizers or croton oil, but not with
      tolerizing analogues. Using a functional assay significantly more TNF alpha was
      found in the supernatants of KCs treated in vitro with DNFB or LPS than with
      DNTB. GM-CSF was found in untreated epidermis as well as in stimulated cells. The
      results suggest that the sensitizing properties of contact sensitizers may partly
      be dependent on their ability to induce proinflammatory mediators. The induction
      and release of TNF alpha and IL-1 alpha in KCs by contact sensitizers may play an
      important role in the early response to immunogenic or inflammatory signals in
      vivo, whereby tolerance induction seems to be less dependent on these cytokines.

PMID- 1365309
TI  - 8-MOP vs 5-MOP.

PMID- 1365310
TI  - Pathogenesis of mechanobullous disorders.
AB  - Recent advances in the molecular biology of the dermo-epidermal basement membrane
      zone have contributed greatly to our understanding of the etiopathogenetic
      pathways underlying mechanobullous disorders. Genetic linkage was established
      between the keratin gene clusters and epidermolysis bullosa simplex, and keratin
      mutations were identified in several patients. Anchoring filaments and the alpha
      6 beta 4 integrin are likely to be affected in junctional EB. Genetic linkage was
      established between the collagen VII gene and both dominant and recessive
      subtypes of dystrophic epidermolysis bullosa, and different molecular
      abnormalities of collagen VII leading to formation of non-functional, rudimentary
      anchoring fibrils were observed in several families. These discoveries that led
      to definition of mutations underlying EB also help us to understand the normal
      physiology and function of the affected structures. They may also point the way
      to new therapeutic strategies for common acquired blistering diseases and
      disturbances of epithelialization in general.

PMID- 1365311
TI  - B-scanning evaluation with image analysis of psoriatic skin.
AB  - Ten psoriatic plaques from different subjects were investigated by 20 MHz
      ultrasound B scanning. Lesions were evaluated before therapy, and after 7 and 15
      days of topical treatment with anthralin. Recordings from lesional skin were
      compared with those from clinically non-involved contralateral skin. Images were
      assessed by means of a new image analysis program, allowing the conversion of the
      B-scan image color scale into a numerical amplitude scale, the selection and
      highlighting of amplitude bands, and the quantification of objects reflecting in
      a definite amplitude range. B-scanning evaluation of the psoriatic plaque
      revealed a thickening of the epidermis and dermis, the presence of parallel
      acoustic shadows in the dermis, and a characteristic hypo-echogenic band
      corresponding to the papillary dermis. Image processing allowed an exact
      quantification of the progressive reduction in thickness of the epidermis and
      dermis and of the hypo-echogenic band observed at skin sites which had been
      treated with topical substances. Thus, the echographic method with image analysis
      allows the evaluation of three different parameters of response to topical
      treatment of psoriatic skin.

PMID- 1365312
TI  - Spleen dendritic cells exhibit altered morphology and increased allostimulatory
      capacity after short-term culture.
AB  - Ia-bearing dendritic cells (DC) are a class of bone marrow-derived antigen
      presenting cells that appear to possess an increased capacity to stimulate
      resting T lymphocytes. DC from different tissues share several morphologic,
      phenotypic and functional attributes. For example, freshly isolated DC from
      spleen resemble phenotypically and functionally freshly isolated Langerhans cells
      (LC) from epidermis; in addition, during short-term culture both DC and LC
      undergo several parallel changes including modifications affecting phenotype,
      capacity to present protein antigens, and ability to route surface Ia molecules
      into intracellular acidic compartments (J Immunol 1990: 145: 2820-2826). In the
      present study we show, using immunoelectron microscopy with anti-Ia and anti-33D1
      monoclonal antibodies, freshly isolated DC in suspension to have a smooth cell
      surface with few and short cytoplasmic projections. By contrast, cultured DC
      display conspicuous bulbous cytoplasmic protrusions. In addition, spleen DC
      following culture for 24-48 hours exhibit an increased ability to stimulated
      allogeneic T lymphocytes in the primary mixed leukocyte reaction. These changes,
      similar to those described for freshly isolated and cultured LC respectively,
      further substantiate the close relationship between DC and LC.

PMID- 1365313
TI  - Differential localization of ICAM-1 and HLA-DR expression on epidermal basal
      surface in mycosis fungoides and lichenoid reaction.
AB  - Scanning electron microscopy with immunogold labeling revealed that epidermal
      keratinocytes expressed ICAM-1 (intercellular adhesion molecule-1) and HLA-DR
      molecules on their surfaces in patterns that differed in mycosis fungoides (MF)
      and lichenoid reaction (LR). ICAM-1 molecules, visualized as deposits of gold
      particle, were visualized as clusters adjacent to the junctions interconnecting
      the keratinocytes of MF lesions. LFA-1 (leukocyte function-associated antigen-1)
      molecules were seen as granules on the surfaces of all infiltrates, most of which
      also expressed ICAM-1. HLA-DR molecules were seen continuously along the borders
      of the individual keratinocytes, thus producing a cobblestone appearance on the
      epidermal undersurface. In contrast, ICAM-1 and HLA-DR were found only sparsely
      on the undersurface of the epidermis from LR. These findings may help to explain
      the differing histological features of MF and LR: ICAM-1 molecules present on the
      intercellular junctions of MF epidermis lead the LFA-1-bearing cells to migrate
      into the interspaces, thus producing epidermotropism. These cells aggregate by
      means of co-expressed ICAM-1 to thus produce Pautrier's microabscess. In LR, the
      minimal expression of ICAm-1 on the epidermal undersurface leaves most
      infiltrates within the dermis, thus producing a band-like infiltrate.

PMID- 1365314
TI  - Circulating immune complexes in patients with psoriasis: do they exist?
AB  - Sera from 16 patients suffering from active psoriasis without arthropathy (2
      guttate, 10 nummular, and 4 mixed type) were examined for the presence of
      circulating immune complexes. Five routine laboratory assay systems were used,
      based on C1q-binding or detection of IgG-coupled C1q and C3-breakdown products.
      In 14 patients, no elevated levels of circulating immune complexes were detected.
      One patient, who additionally suffered from late-phase HIV-1 infection, showed
      C1q-binding activities as well as levels of IgG-coupled C1q and C3-breakdown
      products in four of the assay systems, which indicated the presence of immune
      complexes in his serum. In another patient, with nummular psoriasis, slightly
      elevated levels of circulating immune complexes were measured by two of the assay
      systems. These results question the hypothesis of an essential pathogenic role of
      circulating immune complexes in psoriasis.

PMID- 1365315
TI  - Effects of ultraviolet radiation on the pathogenesis of Mycobacterium
      lepraemurium infection in mice.
AB  - The purpose of this study was to determine whether exposing mice to ultraviolet
      radiation (UVR) would alter the pathogenesis of infection with Mycobacterium
      lepraemurium (MLM), which causes a chronic, progressive, lethal disease in
      susceptible mouse strains. BALB/c mice were irradiated on dorsal skin with
      various doses of UVR from FS40 sunlamps 3 days before infection with MLM in the
      hind footpad. The course of disease was followed by assessing the number of acid
      fast bacteria in the footpad, regional lymph node and spleen, and measuring the
      size of the lesion at the site of MLM infection at various times after infection.
      Mice were also tested periodically for a delayed-type hypersensitivity (DTH)
      response by injecting MLM antigen into the uninfected footpad and measuring
      footpad swelling 24 hours later. Mice treated with a single high dose of UVR (45
      kJ/m2) had significantly more bacteria in the infected footpad, lymph node and
      spleen than unirradiated control animals. They also had larger lesions at the
      site of MLM infection and exhibited significant suppression of the DTH response
      at 3 and 6 months after infection. Injection of mice s.c. in the footpad with MLM
      3d after 45 kJ/m2 UVR reduced the median survival time from 391 to 305 d and
      after i.v. infection from 171 to 139 d. Dose-response studies indicated that
      exposing mice to 2.3 kJ/m2 of UVR, which is approximately 1 minimal erythemal
      dose for this strain, suppressed the DTH response by 50% at 3 months after
      infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1365316
TI  - The biological and clinical significance of helper T-cell subsets in the human.

PMID- 1365317
TI  - Sensitivity of diagnosis of malignant melanoma: a clinicopathologic study with a
      critical assessment of biopsy techniques.
AB  - Although most examples of cutaneous malignant melanoma are easily recognized by
      their clinical appearances, in some cases this serious neoplasm may clinically
      simulate other less serious forms of skin cancer or benign processes. This study
      was undertaken to assess both the sensitivity of clinical diagnosis of cutaneous
      malignant melanoma and the efficacy of biopsies of clinically unsuspected
      melanomas in yielding specimens on which complete and accurate histologic
      assessments could be made. A retrospective analysis of 1784 cases of
      histologically proven melanomas diagnosed between 1985 and 1990 was performed in
      search of lesions not clinically suspected. Biopsy techniques used to sample
      these lesions were subjected to critique of their efficacy in yielding specimens
      that could be accurately diagnosed and completely assessed histologically. Of
      1784 histologically proven primary cutaneous melanomas, 583 were not clinically
      suspected, yielding a sensitivity of 67%. Clinical diagnosis included nevi (33%),
      no diagnosis (17%), multiple diagnoses (13%), basal cell carcinoma (12%),
      keratosis (9%), and lentigo (9%) among others. The biopsy methods used to sample
      these lesions were shave (56%), excisional (24%), punch (11%), curettage (2%),
      and undetermined (6%). Eighty-six percent of shave biopsies could be accurately
      assessed while only 32% of punches and no curettages provided sufficient material
      for both definitive and complete evaluation of melanomas. Eighteen percent of
      specimens histologically reviewed were considered inadequate for complete
      evaluation. In 34%, the actual diagnosis of melanoma was uncertain because of
      inability to assess diagnostic features as a consequence of the biopsy technique.
      Melanoma may be unsuspected clinically in a significant number of cases and may
      be mistaken for less serious cutaneous neoplasms.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1365318
TI  - Percutaneous absorption of azelaic acid in humans.
AB  - Six healthy male volunteers received a single topical treatment with 5 g of an
      anti-acne cream containing 20% azelaic acid (AzA) onto the face, the chest and
      the upper back. One week later 1 g of AzA was given orally to the same subjects
      as aqueous microcrystalline suspension. Following the two treatments the renal
      excretion of the unchanged compound was measured. Analysis included ether
      extraction of the urine, derivatization of extract and HPLC with UV detection.
      After topical application 2.2 +/- 0.7%, and after oral administration 61.2 +/-
      8.8% of the dose had been excreted unchanged with the urine. By comparing both
      amounts, the percutaneous absorption of AzA from the cream was assessed to 3.6%
      of the dermally applied dose.

PMID- 1365319
TI  - Early development of human Merkel cells.
AB  - Human fetal Merkel cells are now generally considered to be epidermal
      derivatives. Previous studies using antibodies against the simple epithelial
      cytokeratins (CKs), 8 and 18, have demonstrated the presence of these cells in
      the epidermis at as early as fetal week 10 to 12. Using antibodies against CK 20
      whose expression within the skin is restricted to Merkel cells, we applied
      immunofluorescence and immunoperoxidase microscopy to analyze earlier embryonic
      and fetal human skin (wk 7 to 9). We were able to demonstrate the first Merkel
      cells at as early as fetal wk 8, i.e., at the same time as the epidermis starts
      to develop an intermediate, third layer, characterized by the expression of CKs
      1, 10, and 11. Most of these early Merkel cells were localized above the basal
      layer. Their shape was round to oval, dendrites being infrequent and short. At
      fetal wk 9, Merkel cells were considerably more numerous. These results
      persuasively argue for a much earlier fetal development of Merkel cells within
      the epidermis than previously thought. A hypothesis concerning the
      differentiation of Merkel cells from embryonic basal keratinocytes is discussed.

PMID- 1365320
TI  - Altered regulation of collagen metabolism in scleroderma fibroblasts grown within
      three-dimensional collagen gels.
AB  - In systemic scleroderma (SSc) excessive deposition of collagen leads to fibrosis
      of various tissues including the skin. Previous studies have demonstrated that
      scleroderma fibroblasts in explant monolayer cultures are heterogeneous with
      respect to their levels of collagen synthesis. The critical role played by the
      extracellular matrix (ECM) in the modulation of fibroblast metabolism prompted us
      to study the regulation of collagen synthesis in scleroderma fibroblasts grown
      within three-dimensional collagen gels, a culture system representing more
      physiological conditions than monolayer cultures. Normal fibroblasts grown in
      this system dramatically reduce their collagen synthesis as compared to monolayer
      cultures. Quantification of total protein and collagen synthesis showed that
      scleroderma fibroblasts did not demonstrate the down regulation of collagen
      synthesis as observed in control fibroblasts, resulting in a much higher collagen
      synthesis in scleroderma fibroblasts compared to controls. However, also in this
      system scleroderma fibroblasts were heterogeneous in their response to the
      collagenous lattice. Ten strains were investigated, of which 3 were
      indistinguishable from controls, while 7 maintained higher levels of collagen
      production. In addition, our data showed that the changes in collagen synthesis
      on the protein level were accompanied by respective up- or downregulation on the
      mRNA level. These results indicate that an altered response to the surrounding
      ECM is an important factor in the disturbed regulation of connective tissue
      synthesis in scleroderma fibroblasts observed in vivo.

PMID- 1365321
TI  - 8-MOP vs 5-MOP.

PMID- 1365322
TI  - Studies and perspectives of signal transduction in the skin.
AB  - Tumor-promoting phorbol ester and epidermal growth factor (EGF) exert marked
      influences on the proliferation and differentiation of keratinocytes. These two
      agents bring their physiological functions into play via protein kinase C (PKC)
      activation (and/or down regulation) and protein tyrosine kinase, respectively. In
      this paper, the present situation in the studies on the signal transduction of
      keratinocytes centering around these two kinases is discussed. An outline of
      studies on signal transduction of cells other than keratinocytes in the skin is
      also given.

PMID- 1365323
TI  - Kalinin is abnormally expressed in epithelial basement membranes of Herlitz's
      junctional epidermolysis bullosa patients.
AB  - Kalinin is an extracellular adhesion molecule specific to epithelial basement
      membranes (BM) identified as a component of anchoring filaments of
      hemidesmosomes. This heterotrimeric protein is synthesized by cultured normal
      human keratinocytes and is involved in cell attachment. In indirect
      immunofluorescence studies, the epidermal BM of patients with junctional
      epidermolysis bullosa (JEB) of Herlitz's type were found not to be reactive with
      the anti-kalinin monoclonal antibodies ka146 and K140 and displayed a decreased
      immunoreactivity to two anti-kalinin antibodies cross-reacting with K-laminin, an
      anchoring filament component recently described. The intrinsic defect of JEB
      keratinocytes in the synthesis of kalinin was further documented by indirect
      immunofluorescence on in vitro cultures of these cells. In non-Herlitz JEB
      patients, staining of BM was constantly detected. Impairment of expression of
      kalinin correlated with the lack of reactivity to the monoclonal antibody GB3,
      which detects the BM component nicein/BM600. These results clearly demonstrate a
      defect of kalinin expression in epithelial basement membranes of Herlitz JEB
      patients and suggest that kalinin may play a role in the pathogenesis of the
      disease. Further studies are in progress to define possible relationships between
      kalinin and nicein.

PMID- 1365324
TI  - A non-radiolabelled in situ hybridization method for the detection of epidermal
      cytokine mRNA.
AB  - We describe a non-radiolabelled method for the in situ detection of epidermal
      cytokine mRNA in paraffin sections of skin biopsies from sites of nickel contact
      sensitivity. The method uses fluorescein isothiocyanate-labelled oligonucleotide
      exon probe cocktails.

PMID- 1365325
TI  - Enhanced antibody titers to an oxidized DNA base in inflammatory and neoplastic
      diseases.
AB  - Reactive oxygen species (ROS) produced by phagocytic cells induce oxidative
      stress during chronic inflammation. ROS play a role in the pathogenesis of a
      broad range of diseases including autoimmune, cardiac and neoplastic
      abnormalities. We found that sera of patients with a variety of inflammatory
      dermatoses contain elevated levels of antibodies (Ab) binding to an oxidized DNA
      base derivative, 5-hydroxymethyl-2'deoxyuridine (HMdU) coupled to bovine serum
      albumin, as determined by the enzyme-linked immunosorbent assay. Patients with
      immune complex diseases and a history of neoplasm elaborated the highest titers
      of anti-HMdU Ab. Titers from sera of psoriatic subjects were lower than from the
      aforementioned groups but were still significantly elevated (p < 0.001) above
      those of healthy controls. Treatment of inflammatory dermatoses with systemic
      antiinflammatory and cytotoxic drugs significantly lowered the titers [p < 0.005
      (immune complex) or p < 0.001 (psoriasis and neoplastic) diseases], suggesting
      that this assay may be of value in monitoring the response to therapy in these
      diseases.

PMID- 1365326
TI  - Adult T-cell leukemia/lymphoma (ATL)--clinical, histopathological, immunological
      and immunohistochemical characteristics.
AB  - Twenty-one patients with ATL were assessed. The predominant physical findings
      were lymph node and bone marrow involvement, skin involvement, hepatosplenomegaly
      and leukemic manifestations. The predominant histopathological findings in both
      skin and lymph node specimens were the diffuse medium-sized cell type and the
      diffuse mixed cell type. Some phenotypic discrepancy was found between the
      neoplastic cells in the peripheral blood, lymph nodes and skin of patients with
      ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25 and HLA-DR. That is,
      the predominant neoplastic cell phenotype was the helper T-cell, which was CD3+,
      CD4+, CD7+, CD25+, CD45RA+ and HLA-DR+, and CD29- and CD45RO- in peripheral blood
      and lymph nodes, and CD3+, CD4+, CD7+, CD29+, CD45RO+ and HLA-DR+, and CD45RA- in
      the skin. In other words, we have described the phenotypic heterogeneity of ATL
      cells and demonstrated the heterogeneity of CD45R isoform expression on ATL cells
      in different organs--the skin, peripheral blood and lymph nodes--of the same
      patient.

PMID- 1365327
TI  - Comparison of skin changes induced on mice by either group A type 12 or group G
      streptococci.
AB  - Adult Swiss webster mice were injected with 3 x 10(6) colony-forming units (cfu)
      of group G or 2.5 x 10(6) cfu of group A streptococci at intradermal injection
      sites on the right and left paralumbar areas of the back. The mice were
      sacrificed at intervals between 4 hours and 14 days post-injection (p.i.) and
      full thickness biopsies of skin 10 mm in diameter encompassing the sites of
      injection were taken. One tissue specimen was homogenized in PBS and plated to
      determine the number of cfu, while another was used for histopathological
      studies. The number of viable group A and group G streptococci in the tissue
      increased to 3 x 10(9) cfu by 96 hours p.i.: after 192 hours p.i. the group A
      cells had declined to 2.7 x 10(6) cfu compared to 1.1 x 10(8) cfu for group G
      cells. No streptococci of either group were detected at 336 hours (14 days p.i.).
      Gross edematous lesions induced by either streptococcus group were evident on all
      animals at 24 hours (p.i.). Group G streptococci lesions were larger and
      persisted longer than lesions induced by group A. Histological examination
      consistently revealed more inflammation and necrosis in tissue sections from mice
      injected with group G streptococci.

PMID- 1365328
TI  - [Cross-reactions between microbes and tissue as an inducer of autoimmune
      responses].

PMID- 1365329
TI  - [Current findings about bone organic connective tissue and its regulation].

PMID- 1365330
TI  - [The natural and supernatural in alternative medicine].

PMID- 1365331
TI  - [Finnish sperm donors].

PMID- 1365332
TI  - [Myoelectric upper arm prosthesis--what, when, for whom?].

PMID- 1365333
TI  - [Does macrocytosis without anemia require more careful studies?].

PMID- 1365334
TI  - [Should an obese elderly person go on a diet?].

PMID- 1365335
TI  - [Interferon is useful in the treatment of chronic hepatitis B].

PMID- 1365336
TI  - [Double pregnancy in 2 separate uteri].

PMID- 1365337
TI  - [Drug therapy of peptic ulcer disease].

PMID- 1365338
TI  - [Finnish coronary heart disease].

PMID- 1365339
TI  - [Why are the incidence and mortality rate in coronary heart disease so high in
      the Finnish population?].

PMID- 1365340
TI  - [Prevention of coronary heart disease in Finland].

PMID- 1365341
TI  - [Coronary heart disease and its risk factors in Finland].

PMID- 1365342
TI  - [Lipoproteins, genetic factors and Finnish coronary heart disease].

PMID- 1365343
TI  - [Is the distribution of lipoproteins unusual in Finland?].

PMID- 1365344
TI  - [Risk factors of coronary heart disease in Finnish children and adolescents].

PMID- 1365345
TI  - [Antioxidants, oxidation of LDL and atherosclerosis].

PMID- 1365346
TI  - [Psychological and social factors in the background of coronary heart disease].

PMID- 1365347
TI  - [Is the Finnish diet atherogenic?].

PMID- 1365348
TI  - [Alcohol consumption and coronary heart disease in Finland].

PMID- 1365349
TI  - [Infections and coronary heart disease].

PMID- 1365350
TI  - [Coagulation factors, platelets and coronary heart disease].

PMID- 1365351
TI  - [Coronary angioplasty and surgical treatment of coronary heart disease].

PMID- 1365352
TI  - [Puerperal psychosis].

PMID- 1365353
TI  - [Kidney diseases associated with hyperlipidemia and its treatment].

PMID- 1365354
TI  - [Prevention of sudden death using implantable defibrillators].

PMID- 1365355
TI  - [The effect of congenital heart disease on social development of adolescents].

PMID- 1365356
TI  - [Are new viruses being found?].

PMID- 1365357
TI  - [Copper, atherosclerosis and coronary heart disease].

PMID- 1365358
TI  - [The gene defect for Finnish hereditary amyloidosis has been found].

PMID- 1365359
TI  - [Traffic and brain].

PMID- 1365360
TI  - [Old brain injuries and driver's licence].

PMID- 1365361
TI  - [Orthostatic tremor].

PMID- 1365362
TI  - [Persistent groin pain as a symptom of a rare disorder].

PMID- 1365363
TI  - [Joint symptoms as a first sign of hemochromatosis].

PMID- 1365364
TI  - [When and how is delayed speech development in children treated?].

PMID- 1365365
TI  - [How are nerves supported--structure and function of connective tissue of
      nerves].

PMID- 1365366
TI  - [Early diagnosis and screening of colonic adenomatous polyposis].

PMID- 1365367
TI  - [Xylitol and caries].

PMID- 1365368
TI  - [Pancreatic islet cell transplantation].

PMID- 1365369
TI  - [Defective gene causing diastrophic dysplasia has been localized].

PMID- 1365370
TI  - [Calcium antagonists and atherosclerosis].

PMID- 1365371
TI  - [Management of esophageal rupture].

PMID- 1365372
TI  - [Depression in a child].

PMID- 1365373
TI  - [Swimming pool granuloma: hand infection caused by Mycobacterium marinum].

PMID- 1365374
TI  - [Acrodermatitis enteropathica in a full-term infant].

PMID- 1365375
TI  - [Guided fine-needle biopsy as a diagnostic method].

PMID- 1365376
TI  - [Chlorophenol predisposition-associated cancer risk in Karkola].

PMID- 1365377
TI  - [Sleep and health].

PMID- 1365378
TI  - [Where and how should patients with sleep disorders be treated?].

PMID- 1365379
TI  - [Shift work, jet lag and sleep].

PMID- 1365380
TI  - [Neurophysiological background of sleep disorders].

PMID- 1365381
TI  - [The clinical-neurophysiological diagnosis of sleep disorders].

PMID- 1365382
TI  - [Sleepless patients in the general practitioner's office].

PMID- 1365383
TI  - [Advantages and disadvantages of sleeping pills].

PMID- 1365384
TI  - [Unusual daytime fatigue: narcolepsy and hypersomnia].

PMID- 1365385
TI  - [Sleep disorders and heart and vascular diseases].

PMID- 1365386
TI  - [Pathophysiology and diagnosis of sleep apnea].

PMID- 1365387
TI  - [Conservative treatment of sleep apnea syndrome].

PMID- 1365388
TI  - [Surgical treatment of obstructive sleep apnea syndrome].

PMID- 1365389
TI  - [Breathing disorders during sleep and their treatment in patients with lung
      diseases].

PMID- 1365390
TI  - [Sleep walking and other parasomnias].

PMID- 1365391
TI  - [Children's sleep disorders and their treatment].

PMID- 1365392
TI  - [Special features of sleep disorders in the elderly].

PMID- 1365393
TI  - Homeobox cooperativity.

PMID- 1365394
TI  - Optimization of the CAT assay procedure by determining the initial rate of the
      enzymatic reaction.

PMID- 1365395
TI  - Mapping the genes that made maize.
AB  - George Beadle proposed that the striking morphological differences between
      cultivated maize and its probable wild progenitor (teosinte) were initiated by a
      small number of mutations with large effects on adult morphology. Recent genetic
      analyses using molecular markers provide some support for this view and show
      where in the maize genome the putative loci are likely to be located. This work
      sets the stage for fine-scale linkage mapping of these genomic regions and the
      eventual cloning of the genes involved in this remarkable evolutionary
      transformation.

PMID- 1365396
TI  - Master genes in mammalian repetitive DNA amplification.
AB  - The analysis of species-specific subfamilies of both the LINE and SINE mammalian
      repetitive DNA families suggests that such subfamilies have arisen by
      amplification of an extremely small group of 'master' genes. In contrast to the
      master genes, the vast majority of both SINEs and LINEs appear to behave like
      psudogenes in their inability to undergo extensive amplification.

PMID- 1365397
TI  - Ordering gene function: the interpretation of epistasis in regulatory
      hierarchies.
AB  - The order of action of genes in a regulatory hierarchy that is governed by a
      signal can often be determined by the method of epistasis analysis, in which the
      phenotype of a double mutant is compared with that of single mutants. The
      epistatic mutation may be in either the upstream or the downstream gene,
      depending on the nature of the two mutations and the type of regulation.
      Nevertheless, when the regulatory hierarchy satisfies certain conditions, simple
      rules allow the position of the epistatic locus in the pathway to be determined
      without detailed knowledge of the nature of the mutations, the pathway, or the
      molecular mechanism of regulation.

PMID- 1365398
TI  - Secretion across the bacterial outer membrane.
AB  - Many bacteria secrete extracellular proteins such as hydrolytic enzymes or
      toxins. In Gram-negative bacteria, secreted proteins must cross the two membranes
      that constitute the cell envelope. Recent studies have identified several
      specific secretion systems that can be classified in three distinct pathways, and
      related systems have been discovered in a wide range of prokaryotic and
      eukaryotic cells.

PMID- 1365399
TI  - Regenerating good sense: RNA editing and trans splicing in plant mitochondria.
AB  - The protein products of plant mitochondrial genes cannot be predicted accurately
      from genomic sequences, since RNA editing modifies almost all mRNA sequences post
      transcriptionally. Furthermore, RNA editing alters leader, trailer and intron
      sequences, and may be required for processing of these sequences. For several
      plant mitochondrial transcripts, processing includes trans splicing, which
      connects exons scattered throughout the genome. The mature transcripts are
      assembled via split group II intron sequences.

PMID- 1365400
TI  - Localization of methanol dehydrogenase in two strains of methylotrophic bacteria
      detected by immunogold labeling.
AB  - Antibodies to methanol dehydrogenase purified from Methylobacterium sp. strain
      AM1 and Methylomonas sp. strain A4 were raised. The antibody preparations were
      used in indirect immunogold labeling studies. With this approach, methanol
      dehydrogenase was found to be preferentially localized to the periplasmic region
      of the methylotroph Methylobacterium sp. strain AM1 and to the intracytoplasmic
      membrane of the methanotroph Methylomonas sp. strain A4. Antibody cross
      reactivity to other methylotrophic bacteria was detected.

PMID- 1365401
TI  - Toxicity and carcinogenicity of hydroquinone in F344/N rats and B6C3F1 mice.
AB  - Toxicology and carcinogenesis studies were conducted by administering
      hydroquinone (more than 99% pure) by gavage to groups of F344/N rats and B6C3F1
      mice of each sex for 14 days, 13 wk or 2 yr. 14-day studies were conducted by
      administering hydroquinone in corn oil to rats at doses ranging from 63 to 1000
      mg/kg body weight and to mice at doses ranging from 31 to 500 mg/kg, 5 days/wk.
      In the 13-wk studies, doses for rats and mice ranged from 25 to 400 mg/kg. At
      those doses showing some indication of toxicity in the 14-day and 13-wk studies,
      the central nervous system, forestomach and liver were identified as target
      organs in both species and renal toxicity was observed in rats. Based on these
      results, 2-yr studies were conducted by administering 0, 25 or 50 mg
      hydroquinone/kg in deionized water by gavage to groups of 65 rats of each sex, 5
      days/wk. Groups of 65 mice of each sex were given 0, 50 or 100 mg/kg on the same
      schedule. 10 rats and 10 mice from each group were killed and evaluated after 15
      months. Mean body weights of high-dose male rats and high-dose mice were approx.
      5-14% lower than those of controls during the second half of the study. No
      differences in survival were observed between dosed and control groups of rats or
      mice. Nearly all male rats and most female rats in all vehicle control and
      exposed groups had nephropathy, which was judged to be more severe in high-dose
      male rats. Hyperplasia of the renal pelvic transitional epithelium and renal
      cortical cysts were increased in male rats. Tubular cell hyperplasia of the
      kidney was seen in two high-dose male rats, and renal tubular adenomas were seen
      in 4/55 low-dose and 8/55 high-dose male rats; none was seen in vehicle controls
      or in female rats. Mononuclear cell leukaemia in female rats occurred with
      increased incidences in the dosed groups (vehicle control, 9/55; low dose, 15/55;
      high dose, 22/55). Compound-related lesions observed in the liver of high-dose
      male mice included anisokaryosis, syncytial alteration and basophilic foci. The
      incidences of hepatocellular neoplasms, primarily adenomas, were increased in
      dosed female mice (3/55; 16/55; 13/55). Follicular cell hyperplasia of the
      thyroid gland was increased in dosed mice.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1365402
TI  - Making a difference: the role of cell-cell interactions in establishing separate
      identities for equivalent cells.

PMID- 1365404
TI  - Dopaminergic systems and their regulation. Satellite meeting of the XIth
      International Congress of Pharmacology. Como, Italy, 8-11 July 1990. Proceedings.

PMID- 1365403
TI  - The nature of Parkinson's disease.

PMID- 1365405
TI  - Molecular mechanisms involved in transport and release of dopamine in primary
      cultures of mesencephalic neurons.

PMID- 1365406
TI  - Simultaneous recording of the release of nigral and striatal dopamine in the
      awake rat.
AB  - The extracellular concentration of dopamine (DA) and 3,4-hydroxyphenylacetic acid
      (DOPAC) were estimated in the substantia nigra and striatum by microdialysis. The
      dialysate content of DA increased at least 10-fold when nomifensine (5 mumol/l)
      was infused into the nigra via the dialysis membrane. To improve the analytical
      chemical detection of DA, nomifensine was infused continually during all the
      dialysis experiments that were carried out in the substantia nigra. Dendritic as
      well as terminal release of DA were inhibited for several hours when the nerve
      impulse flow in dopaminergic neurons was blocked by systemic administration of
      gamma-butyrolacton (750 mg/kg, i.p.). Perfusion of tetrodotoxin through the nigra
      (1 mumol/l) produced a complete disappearance of nigral DA release and a somewhat
      variable decrease in the release of striatal dopamine. When tetrodotoxin was
      infused into the nigra, the DOPAC output from the nigra was unchanged, but
      striatal DOPAC increased to about 300% of controls. These results show that the
      dendritic release of DA fulfills classical release criteria: it possesses an
      effective uptake-mechanism, it is dependent on the opening of fast-sodium
      channels and it is related to drug-induced changes in impulse-flow activity.

PMID- 1365407
TI  - Control of dopamine release by acetylcholine and dynorphin in the striosomal and
      matrix compartments of the cat caudate nucleus.

PMID- 1365408
TI  - Biochemical and functional differences between dopamine formed from endogenous
      tyrosine and exogenous L-dopa in nigrostriatal dopaminergic neurons.

PMID- 1365409
TI  - Highlights of D1 dopamine receptor antagonist research.
AB  - SCH 39166 is now undergoing clinical trials in schizophrenics as a selective D1
      dopamine receptor antagonist. It differs from SCH 23390, the prototype D1
      receptor antagonist, by having reduced affinity for serotonin receptors and a
      longer duration of action in primates, as measured in the squirrel monkey
      conditioned avoidance paradigm. Further studies on this difference in primates
      indicates that it may be attributable to reduced affinity of SCH 39166 compared
      to SCH 23390 for the hepatic glucuronosyltransferase system. Their affinities are
      similar in rats, a species in which both have similar duration of action. These
      and other studies presented are consistent with the novel profile of SCH 39166.

PMID- 1365410
TI  - CNS distribution of D1 receptors: use of a new specific D1 receptor antagonist,
      [3H]SCH39166.
AB  - D1 dopamine receptors have been localized using a radioactive form of a new
      specific antagonist, [3H]SCH39166. This compound has been shown, in in vitro
      binding studies, to be highly selective for the D1 receptor subtype; more so than
      its predecessor, [3H]SCH23390. These ligand binds saturably, reversibly and with
      high affinity. Use of appropriate conditions produces a high signal to noise
      binding ratio to D1 receptors in slide-mounted tissue sections. Autoradiographic
      localization of radiolabeled receptors shows high densities of the D1 receptor
      subtype in such brain structures as the caudate-putamen, nucleus accumbens,
      entopeduncular nucleus, and the substantia nigra pars reticulata. A lower density
      of receptors is found in a few other areas including lamina VI of the cerebral
      cortex. A distinct paucity of binding was apparent in lamina IV of the cerebral
      cortex and in the choroid plexus, two areas thought to have D1 receptors.
      SCH39166 thus represents a superior ligand for obtaining selective labeling of D1
      receptors in autoradiographic and binding studies.

PMID- 1365411
TI  - The effect of continuous and repeated administration of D1 dopamine receptor
      antagonist on midbrain dopamine neurons.

PMID- 1365412
TI  - New classes of selective D-1 dopamine receptor antagonist provide further
      evidence for two directions of D-1:D-2 interaction.
AB  - Initial notions of cooperative/synergistic interactions between D-1 and D-2
      dopamine receptors have been followed by recent evidence suggesting more complex
      forms of D-1:D-2 interaction. Each of the new, putative selective D-1 antagonists
      SCH 39166, NO 756 and A-69024 antagonised typical behavioural responses to the
      selective D-2 agonist RU 24213 and concurrently released atypical behaviour.
      These data extend new notions of both cooperative/synergistic and oppositional D
      1:D-2 interactions in the regulation of typical and atypical behaviours, which
      may involve further subtypes of D-1 and of D-2 receptor.

PMID- 1365413
TI  - SCH 39166, a potential antipsychotic drug, does not evoke movement disorders in
      cebus monkeys.
AB  - Subchronic administration of a neuroleptic in cebus monkeys can reliably mimic
      the abnormal movements produced by these drugs in humans. SCH 39166 is the best
      candidate to test in this model to determine if selective antagonism at the
      dopamine D1 receptor is devoid of these side effects. It has superior selectivity
      for the dopamine D1 site versus several other sites and a significantly longer
      duration in primates than the prototypical D1 antagonist, SCH 23390. In contrast
      to haloperidol, weekly administration of SCH 39166 for 14 weeks did not produce
      abnormal movements but did produce equivalent sedative effects. Thus dopamine D1
      antagonists are uniquely different from D2 antagonists with regards to the
      production of abnormal movements.

PMID- 1365414
TI  - Role of D1 and D2 dopamine receptors in the behavioral effects of cocaine.

PMID- 1365415
TI  - Dopamine D1 and opioid receptor binding changes in the limbic system of sleep
      deprived rats.
AB  - Sleep deprivation induced by the platform technique is considered to be a heavy
      stressful situation in rats. At the end of the sleep deprivation period (72 h)
      the rat displayed particular behavior characterized by wakefulness, a high degree
      of motor and exploratory activity, increased alertness and reactivity to
      environmental stimuli. Our previous results indicated that this behavior was
      potently antagonized by the administration of the D1 selective antagonist SCH
      23390 and by the opioid antagonist naloxone. In this paper we show that
      concomitantly to this behavior, an increased number of D1 receptors associated
      with an increased dopamine-stimulated adenylate cyclase activity is present in
      the limbic system but not in the striatum of these animals. On the contrary, a
      decreased Bmax of mu and delta opioid receptors was found in the same brain area.
      These data suggest an active role of limbic dopamine and opioid systems in the
      generation of arousal and insomnia related to sleep deprivation-induced stress.

PMID- 1365416
TI  - A68930: a potent agonist specific for the dopamine D1 receptor.
AB  - A68930, [1R, 3S] 1-aminomethyl-5,6-dihydroxy-3-phenylisochroman HCl, is a potent,
      partial agonist in the dopamine-sensitive adenylate cyclase model of the D1
      dopamine receptor in fish retina. In the rat caudate-putamen model of the D1
      dopamine receptor, A68930 is a potent (EC50 2.1 nM) full agonist. In contrast,
      A68930 is a much weaker (EC50 = 3,920 nM) full agonist in a biochemical model of
      the D2 dopamine receptor. A68930 also displays weak 2 agonist activity but the
      molecule is virtually inactive at the 1 and beta-adrenoceptors. When tested in
      rats bearing a unilateral 6-OHDA lesion of the nigro-neostriatal neurons, A68930
      elicits prolonged (> 20 hr) contralateral turning.

PMID- 1365417
TI  - Aromatic L-amino acid decarboxylase activity of retina is modulated via aminergic
      receptors.

PMID- 1365418
TI  - The phosphorylation state of DARPP-32, a third messenger for dopamine, is
      regulated by in vivo pharmacological treatments.
AB  - It has been recently proposed that DARPP-32 participates, as third messenger, in
      the mediation of effects induced by dopamine at the cellular level. DARPP-32 is
      indeed localized almost exclusively on dopaminoceptive neurons bearing the D1
      receptor subtype and it is phosphorylated by cAMP-dependent protein kinase. In
      its phospho-form, DARPP-32 acts as an inhibitor of protein phosphatase-1. In vivo
      pharmacological treatment with selective D1 agonists and antagonists induces
      changes in the phosphorylation state of DARPP-32 that can be correlated to
      changes in cAMP, mediated in turn by D1 and D2 receptors. These data demonstrate
      that the measurement of the phosphorylation state of DARPP-32 with the back
      phosphorylation assay can represent a useful biochemical tool to gain further
      insight into the sequence of events elicited by specific dopaminergic drugs in
      vivo.

PMID- 1365419
TI  - Molecular neurobiology of dopamine receptor subtypes.

PMID- 1365420
TI  - Differential turnover rates of D1 dopamine receptors in the brain and retina of
      adult and senescent rats.
AB  - The present study was designed to investigate the turnover rates of D1 dopamine
      receptors in the brain and retina of adult and aged rats. To this aim, we
      monitored the increase in the density of 3H-SCH 23390 binding sites after the
      administration of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline (EEDQ). The results indicate that, in aged rats, the production
      rate of D1 receptors decreases by 41% to 61% in the striatum, nucleus accumbens
      and substantia nigra, whereas a smaller reduction in the degradation rate of
      these receptors is observed (-21% to -40%). In contrast, the production rate of
      D1 receptors in the retina of aged rats remains unchanged, whilst the degradation
      rate decreases by 25%. These alterations in the rates of receptor production and
      degradation may account for the age-related decrease in the density of D1
      dopamine receptors in the striatum, nucleus accumbens and substantia nigra as
      well as for the increase in the density of these receptors in the retina of aged
      rats.

PMID- 1365421
TI  - Dual actions of (-)-stepholidine on dopamine receptor subtypes after substantia
      nigra lesion.
AB  - 1. It was found that the contralateral rotation challenged by (-)-SPD (4 mg/kg,
      ip) in 6-OHDA-lesioned rats had a gradually progressive process with long latent
      period and a maximal response on 63 days after lesion. This steady contralateral
      rotation was preferably antagonized by D-1 antagonist SCH23390 than D-2
      antagonists. During its latent period (-)-SPD exhibited the antagonistic effect
      to APO, while during its period of full response (-)-SPD could potentiate the APO
      induced rotation. 2. In the rats lesioned with kainic acid plus 6-OHDA to destroy
      the SNC and SNR, (-)-SPD and SKF-38393 challenged neither contralateral nor
      ipsilateral rotation, while APO still induced the rotation but towards
      ipsilateral side, just opposite to that in 6-OHDA-lesioned rats. In this case, (
      )-SPD antagonized the response to APO as did SCH 23390. 3. These evidences
      suggest that the agonistic action of (-)-SPD is resulted from D-1 receptor
      subtype at the SNR under supersensitive functional state. The fact that SNR
      lesion could completely eliminate the agonistic action of (-)-SPD further
      indicate that the D-1 receptors in the ipsilateral SNR may be the sites of action
      of (-)-SPD. The dual actions of (-)-SPD are dependent upon the supersensitivity
      of D-1 receptor subtypes which render the antagonistic action to convert into the
      agonistic.

PMID- 1365422
TI  - A new dopamine agonist in dopamine deprived systems: FCE 23884.

PMID- 1365423
TI  - Pharmacological basis for dopamine D-2 receptor diversity.

PMID- 1365424
TI  - Quantitation of isotypes of D2 receptors using solution hybridization.
AB  - Solution hybridization was used to quantitate the expression of the long and
      short splice variants of mRNA coding for the dopamine D2 receptor. Sequences
      corresponding to 450 bases of the coding region of the long form of the third
      intracellular loop and the full-length coding sequences of the long and short
      isoforms of the D2 receptor were amplified using PCR and cloned into a Bluescribe
      (pBS+) vector. Phage polymerases were used to synthesize riboprobes complementary
      to the third intracellular loop. Hybridization was carried out using sense strand
      RNA or total RNA isolated from tissue or cells. After hybridization and digestion
      with nucleases, the hybridization products were size-fractionated on a urea
      acrylamide gel. The RNA coding for the D2 receptor appeared as two distinct
      bands. One band (438 base pairs) represents the long form of the receptor and a
      second band (285 base pairs) represents the short form of the RNA coding for the
      receptor. Quantitation of the amount of RNA present suggests that in the striatum
      the long form of RNA coding for the receptor is expressed at higher levels than
      is the short form. In a cell line containing dopamine receptors derived from the
      pituitary (SUPI), the long form predominates to an even greater extent than in
      the striatum.

PMID- 1365425
TI  - The D2 receptor: an inhibitory receptor which can trigger stimulatory responses.

PMID- 1365426
TI  - In vitro and in vivo acetylcholine release from rat striatum as a functional
      paradigm of signal transduction via a D-2 dopamine receptor.

PMID- 1365427
TI  - Actions of levodopa on rat substantia nigra zona compacta neurons.

PMID- 1365428
TI  - Structure activity relationship and therapeutic uses of dopaminergic ergots.

PMID- 1365429
TI  - Neuropeptides, excitatory amino acid and adenosine A2 receptors regulate D2
      receptors via intramembrane receptor-receptor interactions. Relevance for
      Parkinson's disease and schizophrenia.

PMID- 1365430
TI  - Biochemical and behavioural consequences of interactions between dopaminergic and
      noradrenergic systems in rat prefrontal cortex.

PMID- 1365431
TI  - Dopamine D2 receptor subtypes couple to different second messenger systems.

PMID- 1365432
TI  - Heterologous monoamine reuptake: lack of transmitter specificity of neuron
      specific carriers.
AB  - The effect of systemic administration of desmethylimipramine (DMI), an inhibitor
      of the noradrenaline (NA) reuptake carrier, and of GBR 12909, an inhibitor of the
      dopamine (DA) reuptake carrier, on the in vivo extracellular concentrations of
      dopamine (DA) was studied by transcerebral dialysis in the prefrontal cortex and
      in the dorsal caudate of freely moving rats. In the NA-rich prefrontal cortex
      only DMI increased extracellular DA concentrations whereas in the dorsal caudate
      only GBR 12909 was effective. Haloperidol increased extracellular DA
      concentrations more effectively in the dorsal caudate than in the prefrontal
      cortex. Pretreatment with DMI, which failed to modify the effect of haloperidol
      in the dorsal caudate, potentiated its action in the prefrontal cortex. The
      reverse was obtained after GBR 12909+ haloperidol in the two areas. 6
      hydroxydopamine lesioning of the dorsal NA bundle prevented the ability of DMI to
      increase DA concentrations. The results suggest that reuptake into NA terminals
      is an important mechanism by which DA is cleared from the extracellular space in
      a NA-rich area such as the prefrontal cortex. The elevated extracellular
      concentrations of DA resulting from blockade of such mechanism by tricyclic
      antidepressants may play a role in the therapeutic effects of these drugs.

PMID- 1365433
TI  - Loss of muscarinic regulation of striatal dopamine function in senescence.

PMID- 1365434
TI  - Investigation of the mechanism of glucocorticoid action on dopamine agonist
      sensitivity.

PMID- 1365435
TI  - Dopaminergic regulation of epileptic activity.
AB  - We evaluated the role of dopamine systems in the propagation of epileptic Focal,
      limbic seizures were produced by systemically administered pilocarpine (200
      mg/kg, i.p.); as previously described this dose produces limbic stereotypes but
      neither convulsions nor seizure-related brain damage. The systemic pretreatment
      with D-1, but not D-2, agonists induced convulsions identical to those produced
      by a higher, convulsant dose of pilocarpine (400 mg/kg). Conversely, the
      pretreatment with D-1 receptor antagonists prevented the convulsions whereas the
      D-2 antagonists facilitated the pilocarpine-induced seizures. Furthermore, we
      studied the effects of intracerebral injections of dopamine agents on seizures
      induced by pilocarpine. Nigral microinjection of D-1 agonists strongly induced
      motor seizures in rats treated with the low dose of pilocarpine. On the other
      hand, microinjection of D-1 antagonists prevented the motor seizures induced by
      the high dose of pilocarpine. This study indicates that the two dopamine receptor
      subtypes, D-1 and D-2, exert opposing roles in the control of epilepsy
      propagation. Substantia nigra pars reticulata appears to be primarily involved in
      the dopamine-mediated modulation of seizures.

PMID- 1365436
TI  - Inhibitory effects of mesocortical dopaminergic neurons on their target cells:
      electrophysiological and pharmacological characterization.

PMID- 1365437
TI  - Effects of chronic levodopa on D1 and D2 receptor-mediated striatal output.

PMID- 1365438
TI  - Blockade of N-methyl-D-aspartate receptors potentiates dopaminergic responses in
      the 6-OHDA model of Parkinson: differential role of D-1 and D-2 receptors.
AB  - The non competitive antagonist of N-methyl-D-aspartate (NMDA) receptors MK-801,
      at doses which did not produce any behavioural modification per se, increased by
      about 40% the contralateral turning induced by the dopaminergic (DA) D-1/D-2
      agonist L-dopa in rats bearing a unilateral lesion of the DA nigro striatal
      neurons. Administration of MK-801 in combination with selective agonists of the D
      1 (SKF 38393) or D-2 (LY 171555) receptor, induced an increase of about 280% of D
      1 mediated turning and a 70% decrease of D-2 mediated turning. Analysis of the
      potentiation of L-dopa mediated turning by MK-801 after selective D-1 receptor
      blockade by SCH 23390, revealed that the increase of turning was related to the
      stimulation of D-1 receptors by L-dopa. Immunocytochemical visualization of the
      proto-oncogene c-fos in the caudate-putamen (CPu) of lesioned rats, revealed a
      sparse c-fos positive nuclei in the lesioned CPu of rats treated with SKF 38393
      alone, while after combined administration of MK-801 and SKF 38393 dense
      labelling of nuclei was found. The results indicate that blockade of NMDA
      receptors by MK-801 acts synergistically with D-1 agonists in the induction of
      turning after DA denervation and shows that these changes are correlated with c
      fos induction in specific areas of the CPu.

PMID- 1365439
TI  - Cortical and limbic dopamine and acetylcholine release as neurochemical
      correlates of emotional arousal in both aversive and non-aversive environmental
      changes.

PMID- 1365440
TI  - Heterogeneity and regulation of central dopamine receptor subtypes studied by
      cDNA cloning methodology.

PMID- 1365441
TI  - Cholinergic modulation of dopamine release in corpus striatum and substantia
      nigra of the rat.

PMID- 1365442
TI  - MPTP-induced "parkinsonism" in the goldfish.

PMID- 1365443
TI  - Chronic administration of MPTP to monkeys: behavioural morphological and
      biochemical correlates.

PMID- 1365444
TI  - Selective lesion of the nigrostriatal dopaminergic pathway by MPTP and
      acetaldehyde or diethyldithiocarbamate.
AB  - We have previously reported that diethyldithiocarbamate and acetaldehyde enhance
      MPTP toxicity in mice (Corsini et al. 1986). Here we show that these drugs
      enhance the depletion of dopamine in the striatum and markedly increase MPTP
      induced death of DA neurons in the substantia nigra. This enhancement of MPTP
      toxicity is specific for the nigro-striatal DA pathway and no recovery occurs, at
      least for four months after the treatment. Rats, although they show an MPTP
      induced acute syndrome similar to the that induced in mice by the combined
      treatments, appear to be insensitive to both MPTP alone or to combined treatment
      with diethyldithiocarbamate or acetaldehyde. The selectivity of the permanent
      bilateral lesions of the nigro-striatal pathway make mice treated with
      acetaldehyde or diethyldithiocarbamate and MPTP a simple and reliable model for
      parkinsonism.

PMID- 1365445
TI  - Striatal and non-striatal neurotransmitter changes in MPTP-parkinsonism in rhesus
      monkey: the symptomatic versus the asymptomatic condition.

PMID- 1365446
TI  - The MPTP-treated mouse as a model of parkinsonism: how good is it?

PMID- 1365447
TI  - Degeneration of mesencephalic dopamine neurons in weaver mutant mice.

PMID- 1365448
TI  - Embryonic dopaminergic neuron transplants in MPTP lesioned mouse striatum.
AB  - The aim of this work is to study CNS development and plasticity, and to study the
      mechanisms that allow exogenous embryonic dopaminergic neurons to restore
      transmitter function in the experimental parkinsonism. Recently, we have
      developed a new method that produces a selective degeneration of the dopaminergic
      nigrostriatal system in mice by a combined acetaldehyde/MPTP treatment. This
      procedure results in a selective and irreversible loss of substantia nigra
      dopaminergic neurons in C57BL mice, while other dopaminergic areas of the brain
      are spared. MPTP alone results instead only in a temporary, reversible damage of
      nigro- striatal dopaminergic functions. Embryonic dopaminergic neurons from
      ventral mesencephalon or hypothalamus are implanted in lesioned or normal right
      striata or lateral ventricles. The mesencephalic neurons implanted in a lesioned
      host form a dense network of fibers which establish functional reinnervation of
      the striatum (or caudate-putamen complex). After several months about the entire
      striatal parenchyma appears reinnervated; on average, 20% of the grafted
      mesencephalic dopaminergic cells survive. Implants of embryonic HYP neurons
      instead, show little or no survival. Moreover, dopaminergic mesencephalic neurons
      in control non-lesioned animals show a poor development with little fiber
      outgrowth. These data indicate that interactions between embryonic dopaminergic
      neurons and adult striatal neurons is specific. They also suggest that this
      specificity is sustained by trophic and/or tropic factors possibly produced by
      the lesioned striatum and by putative inhibitory mechanisms of cell migration and
      neuritic outgrowth.

PMID- 1365449
TI  - Improved drug responsiveness following fetal tissue implant for Parkinson's
      disease.

PMID- 1365450
TI  - Imaging of dopamine receptors using PET and SPECT.

PMID- 1365451
TI  - Visualization of dopamine D1, D2 and D3 receptor mRNAs in human and rat brain.
AB  - Using 32P-labelled oligonucleotides derived from the coding regions of dopamine
      D1, D2 and D3 receptor mRNAs we localized cells containing transcripts for these
      receptors in the human (hD1, hD2) and rat brain (rD1, rD2, rD3). Dopamine D1
      receptor mRNA was detected at high levels in neurons of the caudate and putamen
      as well as in the nucleus accumbens in both human and rat brain. In the rat brain
      D1 receptor mRNA was also abundant in the olfactory tubercles and several
      thalamic nuclei. In both species D1 mRNA was absent from the neurons of the
      substantia nigra and the ventral tegmental area as well as from the globus
      pallidus medialis in humans and entopeduncular nucleus in rats. In contrast,
      dopamine D2 receptor mRNA was found in dopaminergic neurons of the substantia
      nigra pars compacta and of the ventral tegmental area. In addition high levels of
      D2 mRNA were detected in neurons of the caudate, putamen and accumbens nuclei,
      the olfactory tubercle and the anterior lobe of pituitary gland. In the rat the
      highest level of hybridization was found in the intermediate lobe of the
      pituitary gland. In the rat brain dopamine D3 mRNA was mainly detected in the
      Islands of Calleja and at lower levels in the anterior nucleus accumbens, the
      medial mammillary nucleus as well as in the bed nucleus of the stria terminalis.
      In general, a good agreement was found between the distribution of transcripts
      and binding sites labelled with the D1 antagonist SCH 23390 or with the D2 ligand
      SDZ 205-502. For D1 receptors, the main exceptions were the absence of mRNA in
      the globus pallidus and the substantia nigra despite the high densities of
      binding sites in these regions. For D2 receptors, regions where binding sites but
      not mRNA were detected included the olfactory bulb, neocortex, hippocampus and
      superior colliculus.

PMID- 1365452
TI  - Clinical classification of dopaminergic effects in parkinsonism.

PMID- 1365453
TI  - Cholecystokinin receptors in relation to brain dopaminergic pathways.

PMID- 1365454
TI  - Expression of rat striatal D1 and D2 dopamine receptor mRNAs: ontogenetic and
      pharmacological studies.
AB  - The developmental characteristics of D1 and D2 dopamine receptor mRNA levels were
      determined by Northern blot analyses. Striatal D1 and D2 receptor mRNAs of male
      Fischer 344 rats were about 60% of adults levels at postnatal day 1 and reached
      their highest measured levels at day 30 (126-139% adults levels) and then
      decreased by day 120 (100%). D1 and D2 receptor densities at day 30 were about 8
      fold higher than at day 1, while mRNA levels showed only a 2-fold increase. The
      highest level of D2 receptor mRNA in midbrain as reached at day 14 (195% adult
      level) while levels at day 1 were 31% higher than dose at day 120. Treatment with
      selective D2 receptor antagonist, haloperidol (0.5 mg/kg/day, s.c., for 2 h, 7,
      14, 21 days or 21 days + 3 days withdrawal) had no effect on Sprague-Dawley rat
      striatal D2 receptor mRNA levels in spite of significant increases in receptor
      density at the later time points. However, the selective D1 receptor antagonist,
      SCH 23390 (0.5 mg/kg/day, s.c.) produced increases in striatal D1 receptors and
      mRNA levels after treatments of 7, 14 and 21 days + 3 days withdrawal.

PMID- 1365455
TI  - Developmental and age-related changes in the D2 dopamine receptor mRNA subtypes
      in rat brain.
AB  - The influence of ontogeny and aging on the D2 dopamine receptor mRNA in rat brain
      were examined using in situ hybridization histochemistry and Northern analysis
      utilizing oligonucleotide probes complementary to the different D2 mRNA subtypes.
      At birth, there was a high level of D2 dopamine receptor mRNA in corpus striatum
      relative to that found in the cerebral cortex and other brain areas. The
      hybridization signal of striatum (using a probe that hybridizes to both the D2A
      and D2B mRNA) increased during the first two postnatal weeks, reached a peak at
      day 16, then declined slightly. The D2A mRNA showed a similar distribution and
      developmental pattern. Intracisternal injection of 6-hydroxydopamine into
      neonates did not significantly alter the increase of the D2 dopamine receptor
      mRNAs, suggesting that neuronal input does not influence the ontogenetic
      development of this mRNA. In striatum, olfactory tubercule and inferior
      colliculus, the D2A mRNA declined between 3 and 24 months of age. By contrast,
      there was an age-related increase in the D2A mRNA in the anterior and
      intermediate lobes of the pituitary. The mRNA for the D2B dopamine receptor
      showed very low but nevertheless detectable levels in striatum, olfactory
      tubercule and pituitary. Like with the D2A mRNA, in 24-month-old rats the D2B
      mRNA declined in striatum and olfactory tubercule and increased in pituitary.
      These results show that there are differential tissue-related changes in the
      mRNAs for the D2 dopamine receptor during both development and aging.

PMID- 1365456
TI  - Dopamine: contributions and legacy of Leon I. Goldberg (1927-1989).

PMID- 1365457
TI  - Biochemical studies on D2-dopamine receptors.

PMID- 1365458
TI  - Alan Horn Memorial Lecture. Selective probes for characterization of dopamine D1
      and D2 receptors.

PMID- 1365459
TI  - Application of functional in vitro model systems or the comparisons of the
      pharmacological characteristics of dopamine autoreceptors and postsynaptic D-2
      receptors.

PMID- 1365460
TI  - New insight into structural and stereochemical requirements for selective, high
      affinity ligands at the dopamine D2 receptor.

PMID- 1365461
TI  - Dopamine autoreceptor signal transduction in the DA cell body: a "current view".

PMID- 1365462
TI  - Signal transduction pathways involved in presynaptic receptor-mediated inhibition
      of dopamine release in rat striatum.

PMID- 1365463
TI  - Presynaptic dopamine autoreceptors and second messengers controlling tyrosine
      hydroxylase activity in rat brain.
AB  - In brain areas enriched of dopaminergic nerve terminals presynaptic dopamine (DA)
      autoreceptors control the state of activation of tyrosine hydroxylase (TH) by
      regulating the extent of phosphorylation of the enzyme. Evidence is presented
      indicating that this autoinhibitory control may involve a decrease in the cyclic
      AMP-dependent activation of TH through an inhibitory coupling of presynaptic DA
      autoreceptors to adenylate cyclase. As indicated by the insensitivity of the DA
      inhibition of TH to changes in the extracellular concentrations of Ca++, to the
      addition of the Ca++ ionophore A 23187 and of different K+ channel blockers, a
      reduction of Ca++ influx and an increase in the K+ channel activity do not seem
      to be involved in the presynaptic regulation of TH activity by DA autoreceptors
      at least under basal conditions.

PMID- 1365464
TI  - Location and molecular cloning of D1 dopamine receptor.
AB  - Recently, our laboratory has purified the D1 dopamine receptor 6600 fold to near
      homogeneity from digitonin solubilized rat striatal membranes using sequential
      affinity, ion exchange, lectin, and size exclusion chromatographies. The
      resulting receptor preparations still retained ligand binding activity (-11,000
      pmol [3H]SCH 23390 bound per mg/protein) and appeared as a single band at 70-80
      kDa on SDS-PAGE. In order to learn more about the sequence and structure of this
      protein, we recently cloned the gene for a human CNS D1 dopamine receptor. This
      gene has an open reading frame of 1388 nucleotides and encoded for a protein with
      a deduced amino acid sequence of 446 residues. When expressed in mammalian cells
      the cloned D1 receptor had all the ligand binding properties expected for a D1
      receptor (SCH 23390 > cis flupenthixol > raclopride and SKF 38393 > apomorphine >
      dopamine > quinpirole). The cloned D1 receptor was found to stimulate adenylyl
      cyclase but not phospholipase C. The message for this D1 dopamine receptor was
      found in caudate, putamen, frontal cortex, and hippocampus, but not in substantia
      nigra, heart, or kidney. These accomplishments now will allow the pursuit of
      biochemical studies of the receptor protein as well as investigations into
      structure/function relationship of the receptor using a molecular biological
      techniques.

PMID- 1365465
TI  - The Na(+)-Ca++ exchanger in central nerve endings: the relationship between its
      pharmacological blockade and dopamine release from tuberoinfundibular
      hypothalamic neurons.
AB  - 2', 4'-Dimethylbenzamiloride (DMB), an inhibitor of Na(+)-Ca++ antiporter dose
      dependently (10-100 microM) inhibited Na(+)-dependent 45Ca++ efflux from brain
      synaptosomes. This compound was also able to stimulate basal release of [3H]DA
      from superfused TIDA neurons. Another amiloride analogue, 5-N-methyl-N
      guanidinocarbonylmethylamiloride (MGCMA, 100-300 microM), which lacks of
      inhibitory properties on the Na(+)-Ca++ antiporter, failed to modify basal [3H]DA
      release from TIDA neurons. In addition, when the antiporter operates as a Ca(++)
      influx pathway, DMB dose-dependently inhibited Na(+)-dependent 45Ca++ uptake in
      brain synaptosomes, whereas it did not prevent K(+)-induced 45Ca++ uptake, which
      reflets the activation of voltage-operated Ca++ channels. Finally DMB inhibited
      ouabain-induced [3H]DA release, which depends on the activation of the Na(+)-Ca++
      exchanger due to the inhibition of the Na+/K(+)-ATPase pump.

PMID- 1365466
TI  - The case for preventive rheumatology.

PMID- 1365467
TI  - A novel in vitro method for investigating cartilage degradation.
AB  - A novel in vitro microassay is described which allows the direct effects of short
      lived cells or transient cell processes on cartilage matrix to be investigated.
      The method involves layering cells onto 2 microns cryostat sections of cartilage
      and assessing matrix integrity with quantitative histochemistry. Rat
      polymorphonuclear neutrophils (PMNs) caused glycosaminoglycan (GAG) loss from
      sections of bovine nasal cartilage. This loss of GAG was greatly enhanced by the
      presence of zymosan, phorbol ester or calcium ionophore. Similar results were
      obtained using human articular cartilage with human PMNs. This technique may be
      useful in the detection of novel chondroprotective agents.

PMID- 1365468
TI  - Drug effects on a novel in vitro model of cartilage breakdown.
AB  - A new in vitro model for studying cartilage breakdown has been utilised in this
      work. Polymorphonuclear neutrophils (PMNs) with phorbol myristate acetate (PMA)
      were layered onto 2 microns cryostat sections of bovine nasal cartilage. After
      incubation, the sections were fixed, stained, and the amount of glycosaminoglycan
      (GAG) contents measured by microdensitometry. PMNs caused GAG loss from sections
      and this was greatly enhanced when the PMNs were activated by PMA. Various
      pharmacological agents were then added to the system, namely acetyl salicylic
      acid, indomethacin, ibuprofen, piroxicam, dexamethasone, D-penicillamine,
      chloroquine and BN50548. The drugs tested had no direct effect on cartilage
      matrix, nor did they affect GAG loss from sections treated with non-stimulated
      PMNs. However, BN50548, a novel protease inhibitor, afforded a dose response
      protection of cartilage section from GAG loss by PMA stimulated PMNs. This model
      may prove to be of value in screening novel antiproteases with chondroprotective
      activity.

PMID- 1365469
TI  - A comparative study of nabumetone and indomethacin in ankylosing spondylitis.
AB  - Forty-two patients with ankylosing spondylitis were entered into a double-blind
      study to compare treatment with indomethacin and a new non-steroidal anti
      inflammatory drug, nabumetone. Clinical, laboratory and side-effect profiles were
      measured over a three month period. Both drugs were effective in relieving pain
      and morning stiffness, indomethacin was better in alleviating general stiffness,
      nabumetone resulted in less side-effects. Objective measurements of spinal
      movements revealed no difference between the two drugs. Nabumetone, available as
      Relifex, appears as effective as indomethacin in relieving the symptoms of
      ankylosing spondylitis and is possibly better tolerated.

PMID- 1365470
TI  - The role of kinin system in joint inflammatory disease.
AB  - Components of the kallikrein-kininogen-kinin are activated in response to noxious
      stimuli (chemical, physical or bacterial), which may lead to excessive release of
      kinins in the synovial joints that may produce inflammatory joint disease. The
      inflammatory changes observed in synovial tissue may be due to activation of B2
      receptors. Kinins also stimulate the synthesis of other pro-inflammatory agents
      (PGs, LTs, histamine, EDRF, PGI2 and PAF) in the inflamed joint. B2 receptor
      antagonists may provide valuable agents as new analgesic drugs. Further, it is
      suggested that substances directed to reduce the activation of KKS may provide a
      pharmacological basis for the synthesis of novel anti-rheumatic or anti
      inflammatory drugs.

PMID- 1365471
TI  - A double blind, placebo controlled study of niflumic acid gel in the treatment of
      acute tendinitis.
AB  - Percutaneously administered niflumic acid gel (Niflugel R, Laboratories UPSA,
      Rueil Malmaison, France) was compared to placebo in a double blind, placebo
      controlled, multicentre study in the treatment of acute upper and lower limb
      tendinitis. Fifty nine subjects were enrolled in three centres and were randomly
      allocated to receive treatment with 2.5% percutaneous niflumic acid gel or
      placebo gel applied three times daily for 7 days. Clinical evaluations were
      carried out on inclusion and after seven days of treatment. The variables
      measured were pain felt by the patient and the investigators' and patients'
      overall evaluation of the treatments' efficacy. The patients also kept a daily
      record of pain scores. Any adverse events that occurred were noted. The results
      showed that niflumic acid gel was significantly better than placebo in improving
      patient signs as regards overall efficacy ratings. Global evaluation of efficacy
      rated by the investigator showed that 25/29 patients (86.2%) were healed or
      improved in the niflumic acid gel group compared with 11/27 patients (40.7%) on
      placebo, p = < 0.01. The overall assessment of tolerance showed no difference
      between groups. Only two minor adverse effects were reported in patients treated
      with niflumic acid gel, and they did not require patients to stop treatment. The
      study findings indicate that treatment with topical niflumic acid gel is
      effective in the treatment of tendinitis and results in improved clinical signs
      at the end of 7 days.

PMID- 1365472
TI  - A clinical comparison of two leading non-steroidal anti-inflammatory drugs.
AB  - One hundred patients with rheumatoid arthritis were entered into a randomised,
      double-blind, cross-over study of naproxen (500 mg b.d.) and diclofenac (50 mg
      t.i.d.). Each treatment period lasted four weeks with a wash-out period of up to
      one week on admission and again between periods of active therapy. Compared with
      baseline, both treatments significantly reduced the duration of morning
      stiffness, Ritchie Articular Index, daytime and night-time pain and produced a
      significant improvement in the disease status. Forty-two non-serious presumed
      side-effects were reported in 21 patients (21%). All were characterised by common
      everyday signs and symptoms. These largely related to the upper gastrointestinal
      tract and typical of those commonly reported for non-steroidal anti-inflammatory
      agents. There were no statistically significant differences between the two
      treatments for any of the efficacy parameters or in the incidence of side
      effects. Patients also expressed an equal preference for the two drugs.

PMID- 1365473
TI  - Variations between rheumatologists in using sulphasalazine.
AB  - The increased use of audit and resource management within the health service will
      focus attention on variations in clinical practice. We have looked at one
      rheumatological example; the extent rheumatologists vary in their clinical use of
      a slow-acting anti-inflammatory drug. We studied a single drug - sulphasalazine.
      In a prospective study sulphasalazine was given to 298 rheumatoid patients at 24
      rheumatology centres in South East England. They were followed for 6 months.
      There were large differences between centres in: the types of patient started on
      therapy; the numbers of patients remaining on treatment; the responses after 6
      months. The difference between some centres was more marked than the expected
      improvement in clinical and laboratory variables given by sulphasalazine. The use
      of a slow acting anti-rheumatic drug like sulphasalazine in rheumatoid arthritis
      is agreed by most rheumatologists in the UK and yet there are wide variations in
      its use. Our results question the validity of comparing clinical practice and
      associated costs between centres for even a simple clinical procedure.

PMID- 1365474
TI  - Four commonly prescribed non-steroidal anti-inflammatory drugs for rheumatoid
      arthritis.
AB  - A four-way single-blind crossover study was used to compare the efficacy and
      tolerance of four non-steroidal anti-inflammatory drugs. In addition, pain
      intensity was compared during the day, at night, at rest, on walking, in the most
      painful joint, and with the patients most painful activity. Ninety-six patients
      with rheumatoid arthritis took single daily doses of controlled release naproxen
      (N), diclofenac S.R. (D), indomethacin S.R. (I) and standard piroxicam (P). The
      greatest changes from baseline after treatment were seen in those patients with
      the highest initial pain measurement scores. Assessments of pain in the morning,
      in the most painful joint and the most painful activity were more discriminating
      than those at noon or at rest. Of the treatments, 'N' and 'P' were the most
      effective in reducing pain, with statistically significant differences from
      baseline. 'I' was the most effective in reducing morning stiffness. Adverse
      experiences were generally mild, occurring more frequently on 'I' than on other
      treatments.

PMID- 1365475
TI  - NSAIDs for the new decade--nabumetone?

PMID- 1365476
TI  - The epidemiology of NSAID associated gastrointestinal disease.
AB  - Many problems make it difficult to estimate the exact risk of peptic ulceration
      and its complications, perforation and bleeding, in patients receiving NSAIDs.
      Nevertheless the association of these events and treatment is now beyond dispute.
      Deaths are a particular problem in the elderly since mortality from peptic ulcer
      disease rises steeply after age 60. Risk factors identified with hospitalisation
      for gastrointestinal problems in patients receiving NSAIDs include age, previous
      gastrointestinal symptoms, corticosteroid use and disability. The risk of death
      is highest in elderly females and is substantial.

PMID- 1365477
TI  - The science--equivalent efficacy and diminished risk.
AB  - Nabumetone is an effective anti-inflammatory drug in models of inflammation and
      in man, comparable in potency to other compounds of this type. It differs from
      other compounds in several important respects. The parent molecule is non-acidic
      and virtually inactive but is transformed to an active metabolite (6MNA) by the
      liver. 6MNA is not excreted in bile and cannot therefore, by reflux from the
      small intestine, reach the stomach. Many other compounds can reach the stomach in
      this way even when given by routes other than oral, for example by suppository.
      Prostaglandin production by the stomach, a protective mechanism, is not markedly
      affected by 6MNA whereas it is suppressed by other NSAIDs. These studies suggest
      a favourable therapeutic ratio for nabumetone.

PMID- 1365478
TI  - Concerns and choices in general practice.
AB  - Osteoarthritis is a common problem in general practice and a major indication for
      NSAIDs. Many patients with osteoarthritis are elderly and therefore particularly
      at risk from adverse reactions. Co-morbidity and co-prescription may lead to drug
      interactions. For these reasons, safe NSAIDs are the first choice for this
      disease.

PMID- 1365479
TI  - Gastroscopic evaluation of the effects of nabumetone on the gastrointestinal
      mucosa of rheumatic patients.
AB  - Endoscopic studies with nabumetone have consistently shown a lower incidence of
      gastro-duodenal erosive lesions than comparable non-steroidal anti-inflammatory
      drugs (NSAIDs) including naproxen and ibuprofen.

PMID- 1365480
TI  - Efficacy and improved safety--a new anti-arthritic agent.
AB  - Long term studies with nabumetone have confirmed that it is an effective NSAID,
      comparable to other agents including aspirin and naproxen. Large scale post
      marketing studies have shown high response rates and good tolerance.

PMID- 1365481
TI  - The long-term U.S. study--a report on outcome and tolerance.
AB  - Altogether 1,912 patients have been enrolled in studies of nabumetone in the
      United States. They were all patients with osteoarthritis or rheumatoid
      arthritis. After completing participation within randomised studies patients were
      entered into an open study which continued for up to five years. These cases
      provide longterm efficacy and safety data for the use of nabumetone. About 25% of
      patients were withdrawn because of lack of efficacy; most of these withdrawals
      were in the first year of therapy. There was a similar picture with side-effects.
      About 12% of patients were withdrawn, mostly in the first year. Many patients
      continued to take nabumetone for five years without adverse effects and with
      continuing efficacy. The numbers of patients in whom nabumetone was stopped due
      to lack of efficacy or an adverse reaction was similar in those aged over 65
      years and in patients aged less than 65 years. These results show that nabumetone
      is a safe and effective anti-inflammatory drug in long term clinical use.

PMID- 1365482
TI  - A rheumatologist's viewpoint.
AB  - Attitudes to prescribing anti-inflammatory drugs have changed considerably over
      the last 25 years and there is now a recognition of the need to balance
      effectiveness with reduced risks of serious adverse reactions. Such serious side
      effects often involve the upper gastrointestinal tract, and there are differences
      between anti-inflammatory drugs in the frequency with which they cause
      significant problems at this site. Anti-inflammatory drugs with a lesser
      propensity to cause gastrointestinal reactions may have an advantage. Several
      risk factors may be important for upper gastrointestinal side-effects including
      sex, age, history of dyspepsia, other diseases and the type of arthritis. Results
      from post-marketing surveillance studies of nabumetone in the United Kingdom and
      the Federal Republic of Germany showed that although patients with a previous
      history of dyspepsia were more likely to stop the drug due to an adverse
      reaction, the majority continued without any problem. Interestingly, patients
      with rheumatoid arthritis were more likely to stop therapy due to side-effects,
      though it was not clear if this was due to their disease or to multi-morbidity.
      Strategies are needed when prescribing anti-inflammatory drugs which take into
      account the type of patient, their disease, and the best drug. In many instances
      this could be nabumetone.

PMID- 1365483
TI  - Increasing the options in NSAID therapy.

PMID- 1365484
TI  - Pharmacokinetic profile of droxicam.
AB  - Droxicam is a new non-steroid anti-inflammatory drug that is a pro-drug of
      piroxicam. The pharmacokinetics of droxicam, both as a single 10mg dose and as a
      multidose regimen of 10 and 20mg/day for 20 consecutive days, have been studied
      in healthy volunteers. Since transformation into piroxicam takes place in the
      gastrointestinal tract, unchanged droxicam was not detected in plasma. After a
      single 10mg dose the value of Tmax was higher than that reported for piroxicam
      (10mg). This effect is a consequence of the process of transformation of droxicam
      into piroxicam. The remaining pharmacokinetical parameters studied were similar
      to those reported in other studies on piroxicam (10mg). After multiple oral
      administration at a dose of 10 and 20mg/day, absorption kinetics of droxicam were
      delayed with respect to those of piroxicam. The other pharmacokinetical
      parameters studied showed no statistically significant differences between
      droxicam and piroxicam. Absorption and elimination of droxicam are independent of
      the administered dose and the bioavailability of droxicam and piroxicam was
      equal. The influence of gastric emptying on droxicam pharmacokinetics and
      bioavailability has been investigated in healthy volunteers. Gastric emptying was
      experimentally modified by use of propantheline and metoclopramide. Following
      modification of gastric emptying, only Tmax underwent significant increase (P <
      0.05). Absorption rate of droxicam was modified but elimination and
      bioavailability did not suffer modification in conditions of altered gastric
      emptying.

PMID- 1365485
TI  - A double-blind randomised controlled trial of droxicam versus indomethacin in
      rheumatoid arthritis.
AB  - This double-blind randomized controlled trial compares the efficacy of droxicam
      (20mg/day) and that of indomethacin (100mg/day) administered to 20 patients (7
      men, 13 women; aged 54.7 +/- 13.2 years) with active classical or definite
      rheumatoid arthritis during 9 weeks, after a 7-day single-blind run-in
      paracetamol (1,500mg/day) period. Evaluations were carried out at weeks 0
      (washout), 1,2,4,6 and 9. After 9 weeks of treatment, both drugs showed a
      statistically significant improvement of joint pain intensity, articular index
      (number of swollen or painful joints and degree of involvement), duration of
      morning stiffness, functional capacity, and level of fatigue. Inter-treatment
      differences at all study intervals were not observed. Grip strength improved only
      in indomethacin-treated patients. Withdrawals due to lack of therapeutic efficacy
      did not occur. Side effects occurred in four patients from each group. One
      patient in the indomethacin group withdrew at the week 1 due to epigastric pain
      and heartburn. In conclusion, droxicam (20mg/day) seems to be as effective as
      indomethacin (100mg/day) in the alleviation of symptoms in patients with
      rheumatoid arthritis.

PMID- 1365486
TI  - Therapeutic activity, clinical and gastric tolerance of 20mg daily dose of
      droxicam in comparison with piroxicam in patients with degenerative joint
      disease.
AB  - The efficacy and safety of droxicam were compared with piroxicam in a pilot study
      in twenty patients with degenerative joint disease. After a one week washout
      period a baseline gastroscopy was carried out. Treatment during the following 4
      weeks was randomised to droxicam or piroxicam. Safety and tolerance parameters
      were monitored at weekly intervals. Pain was evaluated with two visual analogue
      scales (VAS) (patient and investigator). Affected joints, articular index (AI),
      patient's status and a daily living activities questionnaire were also evaluated.
      Another gastroscopy was carried out at the end of the treatment period. Droxicam
      and piroxicam relieved all symptoms significantly without statistically
      significant clinical differences. Both groups showed no drug related side effects
      in the laboratory values. In the gastroscopic examinations two patients of the
      droxicam group and four of piroxicam group had minor gastric erosions after four
      weeks of treatment without any accompanying clinical symptoms.

PMID- 1365487
TI  - Double-blind, randomized and parallel comparison between droxicam and diclofenac
      sodium in patients with coxarthrosis and gonarthrosis.
AB  - This double-blind clinical trial compares droxicam, a new non-steroidal anti
      inflammatory agent and the reference compound diclofenac sodium. After a 7 day
      placebo run-in period, 80 patients with gonarthrosis and coxarthrosis were
      randomized to receive 20mg/day of droxicam and 150mg/day of diclofenac for 6
      weeks. Evaluations were carried out at weeks 0 (placebo run-in), 2,3, and 6. Both
      drugs showed statistically significant improvements in all clinical measurements
      (index of severity, pain intensity, morning stiffness, maximal forced flexion and
      extension of the knee) after 6 weeks of treatment. Investigator's and patient's
      opinions were consistent with these results. The consumption of paracetamol was
      significantly lower amongst patients treated with droxicam. Withdrawals due to
      lack of therapeutic efficacy did not occur. A lower incidence of side effects,
      mostly upper gastrointestinal symptoms, was noticed amongst droxicam-treated
      patients. However, two patients in the droxicam group were withdrawn at week 3
      and two days after week 6 because of epigastric pain and nausea, and cutaneous
      rash, respectively. Both study drugs are of benefit in reducing pain and
      improving joint motion and function in patients with coxarthrosis and
      gonarthrosis.

PMID- 1365488
TI  - Droxicam: a pharmacological and clinical review of a new NSAID.
AB  - Droxicam acts by inhibition of PGE2 varies. Although it belongs to the oxicam
      family, it is characterised by being a pro-drug of piroxicam, the molecule
      undergoing conversion by hydrolysis once dissolved in the digestive tract. This
      allows us to suppose in principle that, there being less contact between the
      active drug (piroxicam) and the gastric mucosa, the side effects in the said
      mucosa would be slight. The studies which have already been performed in healthy
      volunteers and in patients with osteoarthritis and rheumatoid arthritis, to
      evaluate the efficacy and the tolerance of droxicam in patients suffering from
      such clearly inflammatory processes demonstrate an analgesic potential and anti
      inflammatory effects which become noticeable after two weeks of treatment, and
      the drug is well-tolerated.

PMID- 1365489
TI  - Comparative double-blind study of droxicam (new NSAID) versus indomethacin in
      rheumatoid arthritis.
AB  - This randomized, controlled and double-blind clinical trial compares the efficacy
      of droxicam (20mg/day) with that of indomethacin (75mg/day) in 40 RA patients (11
      male, 29 female) aged (+/- SD) 53 +/- 12.5 years. After a 7-day single-blind run
      in placebo period, patients were divided into two groups and treated for 9 weeks.
      Assessments were done at baseline and at the end of the 1st, 2nd, 4th, 6th and
      9th weeks. Both drugs improved significantly the articular pain, the duration of
      morning stiffness, the articular index, the functional status and the degree of
      fatigue. Patient's and doctor's opinions were in accordance with the above
      mentioned results. The effect of both drugs was more noticeable in the first 2
      weeks of treatment. Droxicam was found to be statistically more active than
      indomethacin in alleviating morning stiffness and improving the functional
      status. The improvement of the variables induced by droxicam increased
      progressively throughout the study whereas that induced by indomethacin remained
      unchanged after the 2nd or 4th week of treatment. One patient treated with
      indomethacin withdrew from the study due to staggering and dizziness and several
      patients reported dyspepsia. Droxicam seems to be as effective as indomethacin
      (75mg/day) in the symptomatic relief of RA patients. The possibility of the use
      of droxicam for the relief of morning stiffness is of particular interest.

PMID- 1365490
TI  - A pharmacokinetic study to evaluate the profile of droxicam in elderly healthy
      volunteers after a single oral dose of 20mg.
AB  - A single oral dose pharmacokinetic study in a group of 10 elderly healthy
      volunteers was performed to evaluate the pharmacokinetic profile and the
      potential effect of age on the absorption, distribution and elimination of
      droxicam. After complete medical screening, and informed written consent, one
      dose (20mg) of droxicam was administered to all volunteers, under medical
      supervision. A complete pharmacokinetic profile of the obtained blood plasma
      levels was evaluated over 120 hours. All volunteers completed the study and in
      none did droxicam cause intolerance or side effects. The results showed that
      droxicam absorption, distribution and elimination did not differ substantially
      from reference studies done with young healthy volunteers. The peak mean plasma
      concentration was at 10 hours 1.38 +/- 0.29 microgram/ml, declining slowly,
      reaching 0.24 +/- 0.20 microgram/ml at 120 hours, with a half life of 50.23 +/-
      17.19 hours and an elimination rate constant of 0.015 +/- 0.005 microgram/ml.h-1.
      In comparison to the healthy, young volunteers, the variation was minimal. It can
      be concluded from this study that age causes minimal variations in the absorption
      and distribution of droxicam.

PMID- 1365491
TI  - Adverse events with droxicam in the early clinical trials.
AB  - This study analyses the results of 8 randomized, controlled clinical trials and
      one open study carried out with droxicam (a new NSAID, pro-drug of piroxicam),
      comparing the adverse events and gastrointestinal tolerance of this compound
      against those of the control drugs used in these trials. The frequency of adverse
      events was lower in the droxicam treated patients. Adverse events concerning the
      gastrointestinal area were also lower. No differences were found in the
      distribution of adverse events by age of sex among the drugs compared. The
      pattern of side effects found was that expected in all non-steroidal anti
      inflammatory agents. These results seem to sustain the hypothesis of a better
      tolerance of droxicam than that of piroxicam, indomethacin or diclofenac,
      especially in the gastrointestinal area.

PMID- 1365492
TI  - With sword and scalpel: a surgical odyssey.

PMID- 1365493
TI  - Haematuria: all that glisters is not gold.

PMID- 1365494
TI  - Biokinematics of vehicle impacts, occupant injury and vehicle crashworthiness.

PMID- 1365495
TI  - The changing relationship between general practice and hospital care.

PMID- 1365496
TI  - The unheard cry (diagnosis and management of hip dysplasia in adults).

PMID- 1365497
TI  - Clinical applications of positron emission tomography.

PMID- 1365498
TI  - Lettsomian Lecture. The minimally invasive therapy revolution.

PMID- 1365499
TI  - Neurosurgery past, present and future.

PMID- 1365500
TI  - The annual oration. Command and morale of soldiers in battle.

PMID- 1365502
TI  - [Diagnosis of coronary artery restenosis after radiologic endovascular
      dilatation].
AB  - Altogether 40 patients with stable angina of effort were investigated in a long
      term period after roentgenovascular dilatation of one or two coronary arteries.
      Control coronarography was performed in 22 patients with lowered exercise
      tolerance. A reliable feature in the development of hemodynamically significant
      restenosis and/or "new" coronary stenosis in 11 patients was a combination of
      average and low exercise tolerance with its negative dynamics. For patients with
      I functional class, a sign of restenosis and/or "new" stenosis was the appearance
      of the ischemic shift of the CT-segment on ECG during bicycle testing. An
      efficient selection of patients resulted in increased sensitivity and specificity
      of noninvasive tests.

PMID- 1365501
TI  - [Angiocardiography in the diagnosis of interventricular septum defects in a
      double displacement of great vessels from the right ventricle].
AB  - The paper is devoted to analysis of the results of angiocardiographic
      investigation of 237 patients with a double deflection of great vessels (DDGV)
      from the right ventricle (RV) (the patients ranged in age from 3 months to 23.5
      years) to study the potentialities of the method in the diagnosis of a defect
      position of the interventricular septum (DIVS). Angiographic investigation
      permitted a sufficiently accurate determination of a DIVS position in DDGV from
      the RV. Of paramount importance for determining a DIVS position is the
      establishment of the interrelationships of the latter with the infundibular
      septum and the openings of major arteries. For diagnosis of a DIVS position one
      should necessarily use left and right ventriculography both in standard and axial
      projections.

PMID- 1365503
TI  - [Effect of contrast ventriculography of the left ventricle on coronary
      hemodynamics in patients with ischemic heart disease].
AB  - The effect of left ventricular (LV) contrast ventriculography (VG) on the state
      of intracardiac hemodynamics during the administration of a contrast medium and
      30-40 sec. after it was investigated in 48 CHD patients. It followed retrograde
      catheterization of the left ventricle by a parallel use of two catheters that
      permitted recording intraventricular pressure directly during LV VG. The
      performance of left VG with 76% urografin administered in a dose of 0.6-0.8 ml/kg
      with the rate of 13-15 ml/s produced no significant change in the state of
      intracardiac hemodynamics, relaxation and pumping function of the LV in the
      course of the first three contrasted cardiocycles. Transitory disorder of
      hemodynamics observed in the patients after contrast VG was restored by itself in
      15-20 min.

PMID- 1365504
TI  - [Axillary approach for radiologic endovascular dilatation].
AB  - Basing on the analysis of 39 observed cases, the authors consider various aspects
      of the use of roentgenovascular dilatation by an axillary access : problems of
      methods, indications and contraindications; they also assess the advantages and
      shortcomings of the access.

PMID- 1365505
TI  - [Tolerance to various radiologic contrast agents used for coronary angiography in
      patients with acute myocardial infarction].
AB  - Coronary angiography (CAG) was performed in the acute period of myocardial
      infarction in 41 patients using verografin and in 38 patients using omnipack. In
      a high risk of CAG performance the tolerance of omnipack was better than that of
      verografin. Omnipack causes allergic reactions less frequently, disturbs less
      azote excretory function of the kidneys and myocardial bioelectric activity.

PMID- 1365506
TI  - [Radiodiagnosis of a small amount of fluid in the pericardial cavity].
AB  - X-ray symptomatology of small pericardial effusions was studied on the basis of
      analysis of clinicoroentgenological and echocardiographic investigation of 173
      patients with various chest diseases. Comparison of x-ray and USI results led to
      a conclusion of the effectiveness of polypositional roentgenography for the
      detection of small amounts of fluid in the pericardial cavity.

PMID- 1365507
TI  - [Computed tomography in the diagnosis of colonic cancer].

PMID- 1365508
TI  - [Bone transplant for total hip joint prosthesis (pilot results of magnetic
      resonance tomography)].

PMID- 1365509
TI  - [Some aspects of succession and continuity in pre- and postgraduate course of
      radiodiagnosis].

PMID- 1365510
TI  - [The radiologist is treating].

PMID- 1365511
TI  - [Screen-grid mammography].
AB  - A device and the results of a 3-year performance of cellular grids for
      mammography were described. An increase in the informative value and a decrease
      in radiation exposure of patients were shown during mammography with a cellular
      grid.

PMID- 1365512
TI  - [Some comments on the article of V.B. Antonovich and L.B.Kirichenko "Clinical,
      radiologic endoscopic and morphologic (morphometric) correlations in chronic non
      ulcerative colitis"].

PMID- 1365513
TI  - [Current perspectives for the improvement of diagnosis in gastric cancer
      (Literature review)].

PMID- 1365514
TI  - [Radiologic diagnosis in 1989. (Analytic review of publications in medical
      journals)].

PMID- 1365515
TI  - [Hemangiomatosis of liver and spleen in a female patient: interventional
      radiologic and surgical treatment].

PMID- 1365516
TI  - [Arterial occlusion induced by silicone compound embosil and its components].

PMID- 1365517
TI  - [A device for fixation of electric radiographic image].

PMID- 1365518
TI  - Necrotising fasciitis: an entity revisited.
AB  - Necrotising fasciitis is a disease that still carries a high morbidity and
      mortality despite our better understanding and advances in treatment since 1924
      when Meleney first studied it. In our Department of Orthopaedics, this condition
      appears to be on the increase, and we therefore felt this entity deserved a
      restudy. Since 1985, 15 cases were seen, of which 10 were encountered in 1989.
      There were no recorded case prior to 1985. Our initial results show that the
      background and outcome parallel that of previous authors. Most were elderly with
      some form of underlying chronic disease. The duration from symptom onset to
      presentation was short, with many being in a state of septicaemia at the time of
      admission with fever, metabolic acidosis and marked leucocytosis. Repeated
      desloughings were common, and four ended up with some form of limb amputation. As
      with Meleney's study, the consistent pathogen cultured was B-haemolytic
      streptococcus. Our recommendation is that we should be more aware of this entity
      in view of its fulminant course, with early and aggressive surgical intervention
      being the keystone to management.

PMID- 1365519
TI  - Chlamydial infection in Canada.

PMID- 1365520
TI  - [Fulminant erysipelas].
AB  - An apparent resurgence of invasive and life-threatening group A streptococcal
      infections in young and previously healthy hosts is reported in several
      countries. We report a case of fatal necrotizing fasciitis and review the
      spectrum of these clinical syndromes, including the invasive soft tissue
      infections. This changing pattern of infection could be explained by an increased
      incidence of some serotypes of group A Streptococcus carrying specific virulence
      factors, such as pyrogenic exotoxins.

PMID- 1365521
TI  - Pathogenesis in amebiasis: is it genetic or acquired?

PMID- 1365522
TI  - Pathogenic versus nonpathogenic Entamoeba histolytica.

PMID- 1365523
TI  - Pathogenesis in amebiasis.

PMID- 1365524
TI  - Pathogenesis in amebiasis.

PMID- 1365525
TI  - Respiratory syncytial virus: babies and antibodies.

PMID- 1365526
TI  - Application of crystallography to the design of antiviral agents.
AB  - A historical review of x-ray crystallography introduces basic concepts and
      describes the potential of this science to the rational design of antiviral
      agents. Following a brief introduction to the study of antiviral compounds that
      inhibit early stages of rhino- and enteroviral infections, the impact of
      structural studies on rational drug design is discussed in relation to known
      viral structures.

PMID- 1365528
TI  - Hospital transmission of cytomegalovirus.

PMID- 1365527
TI  - Lessons from Leishmania: a model for investigations of CD4+ subset
      differentiation.
AB  - Infection of inbred mice with Leishmania major remains the best model of human
      infection with visceralizing Leishmania that cause kala-azar. Immunologic
      investigations have correlated the outcome of disease with expansion of different
      subsets of CD4+ cells, designated Th1 and Th2. Although the capacity of fixed
      effector Th1 and Th2 populations to mediate the diverse outcomes of disease
      through the release of soluble cytokines, particularly IFN-gamma and IL-4, has
      been demonstrated, the mechanisms by which these subsets become established
      during infection have not been delineated. This review focuses on known features
      of CD4+ differentiation using other experimental models, and proposes that
      genetic susceptibility to Leishmania can occur if the host has a Th2 precursor
      cell in the memory configuration prior to the time of exposure to organisms,
      perhaps in response to cross-reactive self-peptides. The hypothesis can explain a
      number of puzzling observations in both murine and human disease due to these
      organisms and makes several predictions amenable to experimental testing.

PMID- 1365529
TI  - Biological and social determinants of the Lyme disease problem.
AB  - Lyme disease, presently the most common arthropod-borne disease in the United
      States, is a phenomenon of both medical and social importance. Notwithstanding
      the substantial public health threat posed by Borrelia burgdorferi infection,
      there is reason to suspect that the diagnosis of Lyme disease is made more
      frequently than justified. On the other hand, the current dissatisfaction with
      serologic assays for B. burgdorferi infection may lead some physicians to
      inappropriately abandon consideration of the diagnosis entirely. Either of these
      outcomes of the patient-physician encounter is to be regretted. The Lyme disease
      problem, as I call the current situation, has both biological and social
      determinants.

PMID- 1365530
TI  - Trends and controversies in the prophylaxis and treatment of malaria.
AB  - Several areas of clinical concern and investigation have emerged over the past
      year in the malaria field. Mefloquine prophylaxis has required a change in its
      dosing regimen. Continued monitoring for potential mefloquine toxicity has shown
      this agent to be safe for use for many populations, but not routinely for
      pregnant women or for young children. Chloroquine-resistant Plasmodium vixax may
      be geographically limited currently, but its presence in Irian Jaya has serious
      implications, should be problem spread. The currently available fluoroquinolone
      antibiotics possess antimalarial activity but they have not proven to be
      clinically dependable for the treatment of resistant Plasmodium falciparum
      infections. However, continued investigation of both their mechanisms of action
      and efficacy should not be abandoned. Adjunctive measures for the control of
      mosquito vectors and the prevention of human contact with mosquitoes assume
      greater importance as both pharmacological prophylaxis and therapy for malaria
      infections become increasingly difficult. Health professionals who advise
      travelers to endemic regions should emphasize the use of safe topical repellents
      and residual insecticides, which can be impregnated into bed netting and
      clothing.

PMID- 1365531
TI  - Traveler's diarrhea: new perspectives.
AB  - Despite pre-travel advice about food and water, traveler's diarrhea is the most
      common infectious disease problem for travelers to developing countries. New
      concepts of antimicrobial prophylaxis, combination treatment with antimicrobial
      and antimotility agents and even a new potential vaccine are reviewed.

PMID- 1365532
TI  - Complement receptors, adhesion, and phagocytosis.
AB  - Phagocytosis is an essential component of host defense against invading
      pathogens. Although many cell types can ingest particulate material,
      "professional phagocytes" perform this function much more efficiently than other
      cells because they express unique membrane proteins and signal transduction
      mechanisms. This review addresses the current state of knowledge about the
      process of phagocytosis and its regulation.

PMID- 1365533
TI  - Astroviruses and caliciviruses: emerging enteric pathogens.
AB  - Acute, infectious gastroenteritis is an extremely common disease that contributes
      significantly to morbidity and mortality worldwide. In the United States, it is
      the second most frequent illness encountered in families. While this illness
      generally runs a self-limited course, it may be temporarily incapacitating and
      impact substantially on numbers of days lost from work or school. At present, 30
      40% of infectious gastroenteritis cases in the United States are attributable to
      viral agents, while 20-30% are due to bacteria and parasites. These estimates are
      almost certainly low, since the cause of gastroenteritis is not discernible in
      approximately 40% of the cases, and gastroenteritis may be caused by viruses or
      other pathogens that cannot be identified at this time. Rotavirus and enteric
      adenovirus are two of the most prevalent and well-studied of the viral agents and
      have been reviewed extensively elsewhere. This review focuses on two broad groups
      of small round structured viruses (SRSV), astroviruses and caliciviruses
      (classic, Norwalk, and Norwalk-like). Although recognized in association with
      acute, nonbacterial gastroenteritis since the early 1970s, the study of these
      viruses has been hampered by the relatively low levels of viral shedding in
      feces, difficulty in propagating the virus in cell or organ culture, and the lack
      of widely available, well-standardized reagents for their detection. In spite of
      these obstacles, much has been learned about these viruses using standard
      virologic (electron microscopy, biophysical characterization, immunoassays) and
      epidemiologic methods. More recently, substantial progress has been made in
      studying astroviruses and caliciviruses at the molecular level. Molecular
      techniques are now being used as diagnostic aids to characterize the epidemiology
      of these agents in greater detail.

PMID- 1365534
TI  - Needle exchange or needless exchange? The state of the debate.
AB  - Needle exchange programs have been implemented in many cities around the world to
      slow the spread of human immunodeficiency virus (HIV) infection among injecting
      drug users. Whether these programs are succeeding in reducing HIV incidence is a
      matter of debate, as is the appropriateness of sanctioning the provision of drug
      injection equipment in the midst of a "war on drugs." In a debate swollen with
      emotional arguments on both sides of the issue, scientific research is essential,
      lest discussion of needle exchange becomes needless exchange at the policy level.
      This article briefly outlines and critiques the common arguments for and against
      needle exchange. Following this, a new circulation theory of needle exchange is
      advanced, along with supporting evidence from an ongoing study in New Haven, CT,
      U.S.A. Finally, several open questions relating to the operation of needle
      exchange programs and the behavior of program clients are suggested for further
      investigation.

PMID- 1365535
TI  - Respiratory syncytial virus and ribavirin: quo vadis?
AB  - Respiratory syncytial virus is the major respiratory pathogen in infants and
      young children. Every year, this unique and ubiquitous virus accounts for
      substantial morbidity and occasional mortality in this age group. Until recently,
      therapy for respiratory syncytial virus infections was limited to supportive
      measures such as hydration, supplemental oxygen, and assisted ventilation.
      Therefore, the licensure of ribavirin in 1986 for treatment of respiratory
      syncytial virus infections raised hopes for specific and effective therapy.
      However, the use of ribavirin has been the subject of continuing controversy and
      debate. Despite at least eight controlled clinical trials involving collectively
      over 170 patients treated with ribavirin since 1983, no clear consensus has
      developed regarding which patients should be treated with ribavirin. Major issues
      are weaknesses in the design and methodology of studies that claim treatment
      efficacy, the clinical significance of the demonstrated treatment effects,
      potential teratogenicity to health care workers exposed to aerosolized ribavirin,
      and cost-effectiveness of the intervention. This review will explore each of
      these areas of controversy and consider the unanswered questions to which future
      research must be directed.

PMID- 1365536
TI  - Rigor in clinical trials.

PMID- 1365537
TI  - Entry of Trypanosoma cruzi into eukaryotic cells.
AB  - Trypanosoma cruzi invades a variety of mammalian cells by receptor-ligand
      interactions. In this review two T. cruzi carbohydrate-binding proteins,
      neuraminidase/trans-sialidase and penetrin, are discussed as possibly playing a
      role in parasite entry into mammalian cells.

PMID- 1365538
TI  - Cytomegalovirus vaccines: current status.
AB  - Clinical observations on the natural history of cytomegalovirus (CMV) infections
      in solid organ transplant recipients and in pregnant women and their offspring
      provide the rationale for the development of a CMV vaccine. The Towne live
      vaccine has been shown to be safe and immunogenic in healthy adults. In a double
      blind, placebo-controlled trial in renal transplant recipients, administration of
      Towne vaccine was associated with significant reduction in the incidence of
      severe CMV disease. The use of the Towne vaccine for prevention of symptomatic
      congenital infection deserves further consideration. As an alternative to live
      vaccine, recombinant vectors containing CMV proteins are being developed.

PMID- 1365539
TI  - Pathogenesis of human herpesvirus 6 (HHV-6).
AB  - The newly isolated virus, human herpesvirus 6 (HHV-6), causes exanthem subitum
      (or roseola infantum) as the primary infection. Liver dysfunction and
      neurological disorders are observed during exanthem subitum. Seroepidemiological
      studies have shown that almost all children are infected with HHV-6 about 6-24
      months after birth. This virus also causes other diseases including lymphadenitis
      and infectious mononucleosis-like disease. HHV-6 has cellular tropism for CD4+
      lymphocytes, in which it replicates in vivo. Its transmission is probably
      airborne early in life, mainly from mother to child, because it is often secreted
      in the saliva of healthy adults having antibody to HHV-6. Latent infection
      follows the primary infection and the virus can often be reactivated under
      conditions of immunosuppression such as AIDS or organ transplantations. The site
      of its latent infection is not yet known, but could be monocytes/macrophages.

PMID- 1365540
TI  - Late treatment of HIV infection--is it better?

PMID- 1365541
TI  - Optimal time to initiate anti-HIV therapy: clinical decisions without definitive
      data.

PMID- 1365542
TI  - Adjunctive therapy in bacterial meningitis--what make sense?
AB  - Bacterial meningitis continues to cause morbidity and mortality despite
      bactericidal antibiotic therapy. Experimental studies of pathophysiology reveal
      the bacteria and their surface components within cerebrospinal fluid (CSF) induce
      the release of inflammatory cytokines that promote CSF inflammation, injure the
      cerebral microvasculature and cause brain edema. Adjunctive corticosteroids
      reduce inflammation, ameliorate the pathophysiology, and improve neurologic
      outcome in children. Practical recommendations are made for children and selected
      adults regarding current and future directions of adjunctive therapy.

PMID- 1365543
TI  - Epstein-Barr virus infection in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma develops with extremely high incidence in discrete
      populations and geographic locations. It is consistently associated with the
      ubiquitous Epstein-Barr herpesvirus (EBV). The structure of EBV DNA indicates
      that the tumor is a clonal proliferation that developed subsequent to EBV
      infection. Specific viral genes are consistently expressed within all cells of
      the tumor. This consistent expression may indicate that the viral gene products
      are required for tumor growth. Genetic or environmental factors may affect the
      expression of these critical viral genes or cellular genes and contribute to
      tumor progression.

PMID- 1365544
TI  - Host-parasite interactions in Taenia solium cysticercosis.
AB  - Human neurocysticercosis results from infestation of the central nervous system
      with the metacestode form (tissue cyst) of Taenia solium. Cysticercosis is being
      increasingly recognized as a cause of neurologic symptoms in residents and
      emigrants from developing countries. Taeniid parasites have developed elaborate
      mechanisms to persist in the tissues of their intermediate hosts. The invasive
      larvae, termed oncospheres, are susceptible to antibody and complement. However,
      by the time that the host has generated an antibody response, the parasites have
      begun to transform to the more resistant metacestode form. The metacestodes also
      have means of evading complement-mediated destruction, including paramyosin,
      which inhibits C1q; taeniaestatin, which inhibits both classical and alternate
      pathways (likely by inhibiting factor D and C3 esterase); and sulfated
      polysaccharides, which activate complement away from the parasite. Similarly,
      antibody does not seem to be able to kill the mature metacestode. The parasites
      may even stimulate the host to produce antibody, which could be bound via Fc
      receptors, and used as a source of protein. Finally, taeniaestatin and other
      parasite molecules may interfere with lymphocyte proliferation and macrophage
      function, thus paralyzing the cellular immune response. Because the symptoms of
      neurocysticercosis are typically associated with a brisk inflammatory response,
      we hypothesize that disease is primarily the result of injured or dying
      parasites. This hypothesis raises important questions in assessing the role of
      chemotherapy in the management of neurocysticercosis as well as in evaluation of
      clinical trials, most of which have been uncontrolled.

PMID- 1365545
TI  - The role of mannose-binding proteins in host defense.
AB  - The human mannose-binding protein (MBP) appears to function as an "ante-antibody"
      as its physiological role is in first line host defense. Low baseline serum
      levels are rapidly increased as part of the acute phase reactant and circulating
      MBP can act as a direct opsonin or activate the classical alternative complement
      pathway. MBP appears to selectively recognize an array of apparently disparate
      oligosaccharides that decorate gram-negative and gram-positive bacteria as well
      as certain parasites, yeasts, and fungi. MBP may be considered a "pattern"
      recognition molecule that has homologs in primitive life forms. Its ability to
      distinguish self from nonself indicates that it may play an important role in
      innate immunity.

PMID- 1365546
TI  - The structure and function of the surface lipophosphoglycan on different
      developmental stages of Leishmania promastigotes.
AB  - The differentiation of Leishmania promastigotes from a noninfective procyclic
      stage to an infective metacyclic stage during growth within the midgut of their
      sand fly vectors or within axenic culture is accompanied by structural
      modifications of the surface lipophosphoglycan (LPG). The modifications are of
      two sorts: (a) a two- to three fold increase in size due to an increase in the
      number of phosphorylated saccharide units expressed and (b) a change in the
      composition of the terminal sugars of some of these units. The elongation of LPG
      on metacyclics promotes complement activation and C3 deposition in a nonlethal
      manner, thus opsonizing the promastigotes for attachment and uptake via
      macrophage receptors appropriate for subsequent intracellular survival. The down
      regulation of terminally exposed galactose residues on metacyclic LPG appears to
      permit the selective release of infective-stage organisms from adhesion to midgut
      epithelial cells so as to make them available for subsequent transmission by
      bite.

PMID- 1365547
TI  - Plasmodial hemoglobin degradation: an ordered pathway in a specialized organelle.
AB  - During its intraerythrocytic development, the malarial parasite devours most of
      the hemoglobin in its host cell. This enormous catabolic process is achieved
      through an ordered, efficient degradative pathway that takes place in a
      specialized organelle, the digestive vacuole. The amino acids generated are used
      by the parasite for its growth and maturation; the heme released is polymerized
      into a crystalline matrix called hemozoin. We are beginning to understand the
      special enzymes that participate in this pathway. We do not yet fully understand
      the relative importance of exogenous versus catabolically generated amino acids,
      the function of hemozoin, the mechanism of action of quinoline drugs that
      concentrate in the digestive vacuole, or the mechanism of protection from malaria
      of variant hemoglobin gene carriers.

PMID- 1365548
TI  - Trans-splicing in protozoa and helminths.
AB  - Trans-splicing is defined as the process whereby exons derived from two
      separately transcribed RNAs are joined together. In one type of trans-splicing,
      nuclear pre-mRNAs acquire their 5' terminal exon (the spliced leader) from a
      small spliced leader RNA (SL RNA) via an RNA processing reaction that is directly
      analagous to the removal of intervening sequences (cis-splicing). Such leader
      addition by trans-splicing has been extensively studied in trypanosomatid
      protozoans and in nematodes. This review summarizes recent advances in research
      on trans-splicing in these two systems. Progress in elucidating functionally
      significant sequence elements within SL RNAs and progress in understanding the
      mechanism and biological role of trans-splicing is discussed.

PMID- 1365549
TI  - The present status of the complement fixation test in viral serodiagnosis.
AB  - The complement fixation (CF) procedure has played a significant role in the
      diagnosis of infectious diseases for almost a century. It has accomplished this
      by functioning in serodiagnosis and by antigen identification particularly in
      clinical virology. Although it has been replaced by newer, more sensitive and
      rapid techniques for serodiagnosis, the CF assay is still important as a
      reference standard for clinical laboratories.

PMID- 1365550
TI  - Visual pecking preferences in domestic chicks. Part II. The role of experience in
      their maintenance or not.
AB  - The role of swallowing experience on the maintenance or switching of the basic
      visual preferences in the pecking of young chicks has been investigated using
      both visually attractive and less attractive seeds. It has been shown previously
      that chicks switch their preferences 24 hrs. later if they cannot swallow what
      they visually prefer whereas debeaked birds which are able to swallow large
      attractive seeds maintain their preferences. However, the same experiment made
      with glued seeds shows that the ability to swallow was responsible for the
      maintenance of preferences in debeaked birds. Swallowing appears to have a
      rewarding effect. The possibility of swallowing the visually preferred item seems
      to be the proximate factor which will determine whether experience reinforces
      basic visual preferences or, on the contrary, modify them.

PMID- 1365551
TI  - Master index volumes 31-40.

PMID- 1365552
TI  - Anticardiolipin antibodies in acute rheumatic fever.
AB  - Recent reports describe the association of antiphospholipid antibodies (aPL) with
      chorea or severe heart valve lesions in systemic lupus erythematosus, lupus-like
      disease, or the primary antiphospholipid antibody syndrome. We conducted a case
      series and a case-control investigation of patients with rheumatic fever with
      Sydenham chorea or other manifestations of rheumatic fever for anticardiolipin
      antibodies (aCL) during the acute attack and disease remission. Eighty percent of
      patients were positive for aCL during the rheumatic fever attack vs 40% when
      inactive (p = 0.035); IgG and IgM aCL increased significantly with disease
      activity. Individuals with or without Sydenham chorea were equally positive for
      aCL (76 and 83%, respectively). A significant association was found between IgM
      aCL and carditis: All patients with valvulitis had IgM aCL (100%) vs 37% of
      patients without valvular involvement (p = 0.02). aPL may play a role in the
      pathogenesis of some clinical manifestations of acute rheumatic fever.

PMID- 1365553
TI  - [Salmonella enteritis: new epidemiologic findings and therapeutic efficiency of
      ciprofloxacin].

PMID- 1365554
TI  - "In vitro" study of sulfimidazole, trimethoprim and fluoroquinolones in
      traveller's bowel infections.

PMID- 1365555
TI  - [New prospects for salmonellosis treatment. 66 cases treated with ciprofloxacin].

PMID- 1365556
TI  - [In vitro activity of 8 antibiotics against Campylobacter spp].

PMID- 1365557
TI  - [Prevention and treatment of traveler's diarrhea].

PMID- 1365558
TI  - [Interactions between quinolones and aminophylline in rats genetically
      predisposed to epilepsy].

PMID- 1365559
TI  - [Interactions of antibiotics and immune development].

PMID- 1365560
TI  - [Diagnostic features of antibiotic allergy].

PMID- 1365561
TI  - [Sub-MIC concentrations of rokitamycin inhibit S. aureus' adhesiveness to human
      epithelial cells].

PMID- 1365562
TI  - [Determination of the post-antibiotic effect of fosfomycin trometamol with
      bioluminescence].

PMID- 1365563
TI  - [Renal clearance of rufloxacin in the healthy volunteer].

PMID- 1365564
TI  - [Dynamics of sIgA concentration in bronchial secretions in patients with COBP
      treated with clarithromycin].

PMID- 1365565
TI  - [Bacterial intracellular compartments an intracellular distribution of
      chemoantibiotics].

PMID- 1365566
TI  - [Infective endocarditis].

PMID- 1365567
TI  - [3 cases of Pseudomonas aeruginosa infections of the SNC of iatrogenic etiology].

PMID- 1365568
TI  - [Isolation of Staphylococcus at a neonatal intensive care unit].

PMID- 1365569
TI  - [Infective endocarditis treated with glycopeptides. Report of 17 cases].

PMID- 1365570
TI  - [2 cases of spontaneous pneumothorax due to acute nosocomial bilateral
      staphylococcal bronchopneumonia].

PMID- 1365571
TI  - [Correlations between bacterial flora present in the juice and the gastric mucosa
      and the risk of postoperative infection].

PMID- 1365572
TI  - [Routine isolation of mutants resistant to beta-lactams among gram-negative
      microorganisms].

PMID- 1365573
TI  - [Lipophilic character and antibiotic action].

PMID- 1365574
TI  - [Temporal pattern of ++resistance to ciprofloxacin in urinary infections].

PMID- 1365575
TI  - [Expression of resistance to beta-lactams in coagulase-negative staphylococci].

PMID- 1365576
TI  - [Etiologic diagnosis of pneumonia in the immunocompromised child].

PMID- 1365577
TI  - [Various therapeutic protocols used in genital disease caused by Chlamydia
      trachomatis].

PMID- 1365578
TI  - [Action of ++clarithromycin against mycoplasma and chlamydia].

PMID- 1365579
TI  - [Treatment of acute cystitis: cost-effectiveness analysis of the single dose
      versus conventional therapy].

PMID- 1365580
TI  - [Teicoplanin in the treatment of otorhinolaryngologic infections (ORL) caused by
      gram-positive organisms].

PMID- 1365581
TI  - [Teicoplanin in the treatment of Gam-positive bacterial infections in the
      immunocompromised host].

PMID- 1365582
TI  - [Teicoplanin in the treatment of neonatal staphylococcal infections].

PMID- 1365583
TI  - [Clinical effectiveness of teicoplanin in the treatment of Gram-positive
      bacterial infections in children].

PMID- 1365584
TI  - [Effectiveness of and tolerance to intramuscular imipenem in the treatment of
      infections of different severities].

PMID- 1365585
TI  - [Role of home therapy with ofloxacin in patients with cystic fibrosis (CF)].

PMID- 1365586
TI  - [Carumonam: antibacterial activity in vitro].

PMID- 1365587
TI  - [Treatment of imported malaria in Italy from 1989 and 1990].

PMID- 1365588
TI  - [An emerging concept: pharmacokinetic changes in antibiotics eliminated by the
      kidney in liver diseases. Mechanisms].

PMID- 1365589
TI  - [Imipenem-cilastatin in nosocomial infections in HIV+ patients].

PMID- 1365590
TI  - [AZT induces remission of chronic active C virus hepatitis in subjects with HIV-1
      infection].

PMID- 1365591
TI  - [Resistance to antitubercular agents in mycobacterial infections in HIV-positive
      patients].

PMID- 1365592
TI  - [Anaerobes as opportunistic agents in HIV infections].

PMID- 1365593
TI  - [Primary treatment of cryptococcosis in AIDS: itraconazole in single dose or
      combined with 5-fluorocytosine].

PMID- 1365594
TI  - [Structure-activity relationship of several mitoxantrone analogues].

PMID- 1365595
TI  - [Bone marrow protection by immunomodulators in antineoplastic chemotherapy].

PMID- 1365596
TI  - [Carcinoma of the anal canal in HIV+ subjects. Description of a case and
      therapeutic strategy].

PMID- 1365597
TI  - [Response to an alternated chemo-radiotherapeutic treatment as neoadjuvant
      therapy of non-small-cell lung carcinoma (NSCLC). Report of a clinical case].

PMID- 1365598
TI  - [The use of interferon alfa-2 in the local treatment of mucocutaneous lesions].

PMID- 1365599
TI  - [Interactions between intestinal microflora and drugs: local and systemic
      effects].

PMID- 1365600
TI  - [Antibacterial agents and neurotransmission].

PMID- 1365601
TI  - New aspects in the diagnosis and treatment of infectious diarrhoea.

PMID- 1365602
TI  - [Potential genotoxic risk of antimicrobial agents].

PMID- 1365603
TI  - Anti-infectious activity of non-antibiotic drugs and their interactions with
      antibiotics.

PMID- 1365604
TI  - [Prosthetic valve endocarditis. Review of 57 cases].

PMID- 1365605
TI  - [Therapeutic problems in pulmonary infections in the immunocompromised child].

PMID- 1365606
TI  - [The use of teicoplanin in staphylococcal infections in the newborn].

PMID- 1365607
TI  - [Treatment of bacterial meningitis in childhood. New aspects and personal
      caseload].

PMID- 1365608
TI  - [Diagnosis and treatment of cytomegalovirus (CMV) infections in the fetus and the
      newborn].

PMID- 1365609
TI  - [From cervico-vaginitis to PID: therapeutic prospects].

PMID- 1365610
TI  - [Treatment of syphilis].

PMID- 1365611
TI  - [The use of pefloxacin and spectinomycin in the treatment of gonorrhea].

PMID- 1365612
TI  - [Treatment of recurrent herpes simplex genitalis].

PMID- 1365613
TI  - [Treatment of non-gonococcal urethritis].

PMID- 1365614
TI  - [Protocol of antibiotic chemoprophylaxis in general surgery].

PMID- 1365615
TI  - [Pathologic findings in migrants from developing countries: the experience of the
      S. Chiara di Palermo ambulatory polyclinic].
AB  - Immigrants are frequently considered as carriers of unknown and/or exotic
      diseases. On the basis of data collected by a working unit of Palermo,
      specifically devoted to the immigrants, we may affirm that the more frequent
      medical problems (67.1%) were of internal origin (especially gastro-enterologic,
      rheumatologic and dermatologic) with an important psycho-somatic component.
      Infections were less common (20%) especially related to respiratory diseases.
      Other more dangerous infections, as Tbc and HIV related diseases, were rather
      infrequent (3%). As a whole, our data demonstrate that control and surveillance
      of migrants are necessary in order to avoid diffusion of pathologies among these
      (compromised) hosts. The risk of transfer of infections to residents is rather
      low.

PMID- 1365616
TI  - The future of antifungal drug research.

PMID- 1365617
TI  - [Chemoprophylaxis and chemotherapy of malaria in the 90s].

PMID- 1365618
TI  - [Antineoplastic chemotherapy in patients with HIV infection].

PMID- 1365619
TI  - [Possibilities of chemoprophylaxis and chemotherapy in protozoan opportunistic
      infections].

PMID- 1365620
TI  - [Opportunistic infections and tumors in AIDS].

PMID- 1365622
TI  - [Cell resistance in oncology. Therapeutic prospects].

PMID- 1365621
TI  - [Clinico-therapeutic features of pulmonary pneumocystis in the patient with
      AIDS].

PMID- 1365623
TI  - [Anthracycline++ resistance and possibilities of overcoming it].

PMID- 1365624
TI  - Preliminary evidence for methamphetamine-induced behavioral and ocular effects in
      rat offspring following exposure during early organogenesis.
AB  - Gravid Sprague-Dawley CD (VAF) rats received 50 mg/kg (d,l)-methamphetamine (MA)
      HCl (expressed as free base, N = 15) or distilled water (N = 6) by SC injection x
      2/day in a 3 ml/kg volume on embryonic (E) days 7-12. Control rats were pair-fed
      to MA-exposed dams on days E7-18. No control dams failed to deliver; however, of
      15 MA-exposed dams 4 did not deliver (2 died and 2 had completely resorbed
      litters). One additional MA litter had all the offspring die shortly after birth.
      There was no difference between groups on offspring postnatal (P) body weight.
      The offspring exposed prenatally to MA had significantly lower olfactory
      orientation scores (P9, 11, 13) to their home cage scent. In a test of early
      activity (P10, 12, 14) the MA-exposed progeny were marginally less active than
      controls. MA-exposed offspring exhibited hyperreactivity and marginally shortened
      response latency on a test of acoustic startle (P27). Motor activity showed no
      differential response in MA treated or control offspring to MA (P63) or
      fluoxetine challenge (P70). However, the MA offspring were more active than
      controls with respect to central and side activity during the second week of
      testing. No group differences were found for performance in a straight swimming
      channel or on the number of errors committed or latency to escape in a complex
      (Cincinnati) water maze (P84). Prenatal exposure to MA also induced eye defects
      (i.e., anophthalmia, microphthalmia and folded retina) in 16.7% of the progeny.
      However, MA did not effect hippocampal or neostriatal monoamine levels when
      measured on P28.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1365625
TI  - Effects of ketanserin and mianserin on delayed neuronal death induced by cerebral
      ischemia in Mongolian gerbils.
AB  - We examined whether ketanserin and mianserin, drugs with 5-HT2 receptor
      antagonistic effects, would have protective effects in Mongolian gerbils on
      delayed neuronal death induced by cerebral ischemia. When training and test
      sessions in the passive avoidance task were carried out 6 and 7 days after 3 min
      of ischemia, passive avoidance impairment was apparent. Destruction and
      disappearance was apparent in the hippocampal CA1 neurons at 7 days after the
      induced ischemia. Administration of ketanserin (5-20 mg/kg) and mianserin (5-20
      mg/kg) led to better passive avoidance and prevented the delayed neuronal death
      induced by the ischemia. These effects of ketanserin and mianserin were not
      inhibited by treatment with the cholinergic blocker scopolamine (5 mg/kg). Thus,
      ketanserin and mianserin have a protective effect on delayed neuronal death in
      gerbils and the effects of these drugs are not mediated by serotonergic and
      cholinergic systems.

PMID- 1365626
TI  - Decreased sensory responsiveness of noradrenergic neurons in the rat locus
      coeruleus following phencyclidine or dizocilpine (MK-801): role of NMDA
      antagonism.
AB  - The effects of the schizophrenomimetic compound phencyclidine (PCP) on baseline
      activity and sensory-evoked responses of noradrenergic locus coeruleus neurons
      were studied with extracellular single-cell recording techniques in the chloral
      hydrate-anaesthetized male albino rat. PCP dose-dependently decreased firing
      rate, induced a more regular firing pattern of the neurons, and decreased
      neuronal responses to a peripheral sensory stimulus (electrical stimulation of
      the hindpaw). These effects of PCP were significantly decreased by pretreatment
      with reserpine or yohimbine, indicating that the effects of PCP were largely
      indirect and mediated through noradrenaline, i.e. by inhibition of its re-uptake,
      resulting in stimulation of alpha 2 autoreceptors. The effects of PCP were,
      however, mimicked by dizocilpine (MK-801), a selective non-competitive antagonist
      at excitatory amino acid receptors of the N-methyl-D-aspartate (NMDA) sub-type,
      suggesting a role also for NMDA receptors in the suppression of sensory
      responsiveness of locus coeruleus neurons by PCP. In view of the purported
      physiological role of the locus coeruleus, this effect of PCP may well contribute
      to the psychotomimetic properties of the drug.

PMID- 1365627
TI  - Different capability of N-methyl-D-aspartate antagonists to elicit EEG and
      behavioural phencyclidine-like effects in rats.
AB  - Phencyclidine (PCP), a drug inducing schizophrenia-like symptoms in humans, is
      reported to be a non-competitive antagonist at the N-methyl-D-aspartate (NMDA)
      subtype of excitatory amino acid receptors. In rats, PCP produces three dose
      dependent stages of EEG patterns: 1) increase of cortical desynchronization
      duration; 2) increase of the amplitude of the high-frequency (20-30 Hz) low
      voltage (30-50 microV) cortical background activity; 3) appearance of cortical
      slow (2-3 Hz) wave-sharp wave complexes. These EEG changes are accompanied by
      stimulatory-depressive effects such as stereotypy (circling, head weaving) and
      ataxia. In the present study, the EEG and behavioural effects induced by systemic
      administration of the NMDA antagonists dizocilpine (MK 801), dextromethorphan
      (DM), [(+)-alpha-(4-chlorophenyl)-4- [(phenyl)methyl-1-piperidine ethanol] (SL
      82.0715), (+)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), cis-4
      phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755) have been compared to
      those of PCP in rats. The rank of potency for inducing PCP-like EEG stages 1-3
      was as follows: MK 801 > PCP > CGS 19755 > CPP. These drugs also induced PCP-like
      behavioural effects. On the contrary, DM and SL 82.0715, administered up to the
      dose of 100 mg/kg IP, failed to induce PCP-like behavioural effects and elicited
      only the stage 1 of PCP-like EEG. These results strongly suggest the involvement
      of NMDA neurotransmission in the behavioral and EEG effects of PCP.

PMID- 1365628
TI  - No psychophysiological interactions between caffeine and stress?
AB  - In earlier studies, the predominantly beta-adrenergic effects of mental tasks and
      the alpha-adrenergic effects of caffeine on cardiovascular functions were
      observed to be simply additive without interaction. In the present study,
      annoying electrical shocks were superimposed on a mental task affording either
      active coping, which specifically raises beta-adrenergic activation, or passive
      coping, and the 40 female subjects were preselected so as to differ in subjective
      stress susceptibility. Caffeine as well as the type of coping and the considered
      personality dimension produced significant effects, but almost no interactions
      were obtained. The stress resistant subjects, who tended toward more
      extraversion, emotional stability and more masculinity, had lower anxiety scores,
      rated their performance higher and had a greater cardiac output than the stress
      non-resistant subjects, who represented a rather normal population according to
      the FPI personality dimensions. Caffeine increased EEG alpha and beta frequency
      and delta power and decreased beta power, raised blood pressure and enhanced
      stress reactions in respiration amplitude and pre-ejection period. Active stress
      coping induced greater stress reactions in heart rate (increase), left
      ventricular ejection time (decrease) and ear pulse arrival time (decrease) than
      passive coping.

PMID- 1365629
TI  - Pharmacological profile of a potent, efficacious fentanyl derivative in rhesus
      monkeys.
AB  - The recent synthesis of fentanyl derivatives, some of which appear to have novel
      profiles of pharmacological effects, has provided compelling evidence that mu
      opioid efficacy might be altered systematically by modifications in the parent
      compound fentanyl. In the present study a new 4-(heteroanilido)-piperidine,
      compound 28, was studied for its effects in rhesus monkeys. In self
      administration studies compound 28 maintained rates of lever pressing similar to
      those maintained by alfentanil; the reinforcing effects of compound 28 were
      attenuated by the opioid antagonist quadazocine. In drug discrimination studies
      compound 28 did not substitute for the kappa agonist ethylketocyclazocine and did
      substitute for the mu agonist alfentanil. In morphine-treated subjects
      discriminating between saline and naltrexone, compound 28 did not substitute for
      naltrexone; however, in morphine-abstinent subjects compound 28 reversed
      naltrexone lever responding. Moreover, this discriminative stimulus effect in
      morphine-abstinent subjects was antagonized by naltrexone and by quadazocine in a
      manner consistent with mu receptor mediation. Compound 28 also was an effective
      analgesic in a warm-water, tail-withdrawal procedure and it decreased markedly
      respiratory function. The analgesic effects as well as the respiratory depressant
      effects of compound 28 were antagonized by quadazocine. Together, these results
      show compound 28 to be a potent, efficacious mu agonist of similar potency to
      alfentanil. Large differences in apparent efficacy at mu receptors between
      compound 28 and another compound in this series (mirfentanil), clearly
      demonstrate that, within this chemical family, small chemical changes can confer
      significant differences in pharmacologic effect.

PMID- 1365630
TI  - Adrenalectomy reverses chronic injection-induced tolerance to nicotine.
AB  - A recent study from our laboratory has demonstrated that C57BL/6 male mice that
      are chronically injected with nicotine develop a profound tolerance to nicotine
      that is not associated with changes in brain nicotinic receptors. We have
      proposed that alterations in the secretion of corticosterone (CCS) may regulate
      tolerance development in chronically injected animals. In the present study we
      have directly tested this hypothesis. Female DBA/2 mice were injected three times
      each day for 12 days with saline or 2 mg/kg nicotine. Blood samples were
      collected at various time points during the course of treatment and plasma CCS
      levels were determined. The animals were divided into two groups following the
      last injection on day 12. The first group of animals was tested for nicotine
      induced release of corticosterone on day 13 of the experiment and then
      sacrificed. The brains of these animals were subsequently used to measure
      nicotinic receptor binding. The second group of animals was adrenalectomized
      (ADX) or sham-operated on day 13 of the experiment and tested for nicotine
      sensitivity on day 14 of the experiment. Plasma CCS levels were significantly
      elevated in animals that were chronically injected with nicotine (versus saline
      controls) by the fourth day of the experiment. Chronic nicotine-injected animals
      were tolerant to nicotine-induced CCS release. Animals that were chronically
      injected with nicotine and sham-operated were tolerant to acute nicotine
      challenge; however, tolerance to nicotine was not detected in ADX animals. These
      data support the hypothesis that the capacity to release CCS may underscore the
      expression of tolerance to nicotine in chronically injected animals.

PMID- 1365631
TI  - Desmethylimipramine attenuates cocaine withdrawal in rats.
AB  - Depression and anhedonia are two major symptoms of cocaine withdrawal in humans.
      Hence, pharmacological treatments effective in depression might also alleviate
      the symptoms of cocaine withdrawal. In the present study, the effects of acute
      and repeated administration of a tricyclic antidepressant, desmethylimipramine
      (DMI), were investigated in naive and cocaine-withdrawing rats. An animal model
      of cocaine withdrawal was used that employs the elevation in intracranial self
      stimulation (ICSS) thresholds following the termination of prolonged periods of
      cocaine self-administration as a measure of an animal's "anhedonic" state. The
      influence of chronic DMI treatment on beta-adrenergic receptor binding and
      affinity was also correlated with the behavioral signs of cocaine withdrawal.
      Neither acute nor repeated DMI treatment influenced reward functions in rats that
      were not undergoing cocaine withdrawal. However, repeated DMI treatment
      significantly down-regulated beta-adrenergic receptors, and shortened the
      duration of the post-cocaine "anhedonia" (elevation in thresholds). Furthermore,
      the magnitude of the beta-adrenergic receptor down-regulation correlated
      significantly with the degree of effectiveness of DMI treatment in reversing the
      post-cocaine "anhedonia". However, chronic DMI treatment did reduce the amount of
      cocaine self-administered by the animals. The reversal of the post-cocaine
      anhedonia in this animal model of cocaine withdrawal by chronic DMI treatment
      demonstrates the potential usefulness of the model in identifying new
      pharmacotherapies for cocaine withdrawal. In addition, the results indicate that
      tricyclic antidepressants may be able to ameliorate some of the symptoms of
      cocaine withdrawal.

PMID- 1365632
TI  - Anxiolytic effects of nitrous oxide in mice in the light-dark and holeboard
      exploratory tests.
AB  - To investigate anxiolytic effects of nitrous oxide (N2O), male mice were tested
      in two exploratory models--a two-chambered light-dark (L-D) unit and a holeboard.
      Tests were conducted inside a glovebag through which one of three mixtures of N2O
      and oxygen (25, 50 and 75% N2O) or room air (RA) was circulated at a flow rate of
      10 l/min. The principal findings in the L-D unit were a concentration-related
      increase in number of interdepartmental transitions and a generalized increase in
      time spent on the light side. Nitrous oxide effectively elevated transitions in
      the L-D unit at a lower concentration (25% N2O) than was required to increase
      locomotor activity in an open field (50% N2O), suggesting that these two measures
      are at least partially independent; transitions might reflect a specific
      exploratory component of locomotor behavior. In the holeboard test, a
      concentration-related increase in number of head dips was observed. Pretreatment
      with naltrexone-HCl or saline vehicle revealed a contribution by an endogenous
      opioid-linked locomotor stimulant effect in some measures. A dose-related
      reversal by flumazenil of 50% N2O-induced shifts in number of head dips and time
      spent head-dipping implicates a benzodiazepine receptor. Both paradigms, in
      particular the holeboard, should prove useful in future N2O research.

PMID- 1365633
TI  - Effects of physostigmine and scopolamine on rats' performances in object
      recognition and radial-maze tests.
AB  - The effects of physostigmine and scopolamine were evaluated on working memory of
      rats in object recognition and radial-maze tests. Three doses of physostigmine
      hemi-sulfate (Phys: 0.05, 0.10 and 0.20 mg/kg), five doses of scopolamine
      hydrobromide (Scop: 0.125, 0.25, 0.5, 1.0 and 2.0 mg/kg), and one dose of
      scopolamine methylbromide (Mscop: 2.0 mg/kg) were used. In object recognition
      test, rats were submitted to three or four intertrial delay conditions (1-min, 15
      min and either 60-min or 24-h). The higher doses of Scop (1.0 and 2.0 mg/kg) in 1
      min and 15-min delay and of Phys (0.20 mg/kg) in 1-min delay impaired
      discrimination between new and familiar objects. Mscop impaired discrimination
      between objects in 60-min but not in 1-min and 15-min delay. This effect may be
      state dependent. Radial-maze learning was impaired by the lower doses of
      scopolamine (0.25 and 0.50 mg/kg) which had no effect in object recognition test.
      These results show that in our conditions, object recognition is less sensitive
      than radial-maze test to cholinergic drugs.

PMID- 1365634
TI  - N-methyl-D-aspartate lesions of the lateral hypothalamus do not reduce
      amphetamine or fenfluramine anorexia but enhance the acquisition of eating in
      response to tail pinch in the rat.
AB  - These experiments examine the acquisition of tail pinch-induced eating and
      responses to the anorectic agents d-amphetamine and d,l-fenfluramine by rats
      bearing N-methyl-D-aspartate (NMDA) lesions of the lateral hypothalamus. Lesioned
      rats lost weight following surgery but had no significant eating or drinking
      difficulties in the home cage (Clark et al. 1990). The acquisition of eating in
      response to tail pinch was enhanced in lateral hypothalamic-lesioned rats: they
      ate on earlier test sessions than controls and less pressure was required to
      elicit eating. Home cage food intake over the period when tail pinch was being
      examined was not affected by the lateral hypothalamic lesions. There were no
      significant differences between lateral hypothalamic-lesioned and control rats in
      terms of their anorectic responses to either d-amphetamine or d,l-fenfluramine,
      though the lesioned rats had a lower baseline intake. These data suggest that the
      lateral hypothalamus is not an important site for the mediation of amphetamine or
      fenfluramine anorexia but is involved in the acquisition of tail pinch-induced
      eating. The disinhibition of responding to tail pinch by lateral hypothalamic
      lesions is discussed in terms of the possible role the lateral hypothalamus plays
      in regulating cortical activity. The role of the medial hypothalamus and non
      hypothalamic systems in the response to anorectic drugs and tail pinch is
      discussed.

PMID- 1365636
TI  - Strain differences in sensitivity to the hypothermic effects of benzodiazepine
      receptor ligands in mice.
AB  - The hypothermic effects of intraperitoneal (IP) administration of the full
      benzodiazepine agonist loprazolam (1, 10 mg/kg); the partial agonist Ro 17-1812
      (1, 10 mg/kg); the benzodiazepine receptor antagonist flumazenil (10, 20 mg/kg);
      the benzodiazepine inverse agonists Ro 15-4513 (1, 3, 10 mg/kg) and Ro 19-4603
      (0.03, 0.1, 0.3 mg/kg) and the beta-carboline inverse agonists FG 7142 (10, 30
      mg/kg) and DMCM (1, 3, 10 mg/kg) were investigated in three strains of mice. TO
      mice were less sensitive than CBA/cA and DBA/2 mice, since only loprazolam and
      the partial and full beta-carboline inverse agonists FG 7142 and DMCM lowered
      body temperature in these animals. CBA/cA mice were particularly sensitive to the
      hypothermic effects of loprazolam and Ro 17-1812, and also responded to the beta
      carboline but not the benzo diazepine inverse agonists. In contrast, DBA/2 mice
      responded with moderate hypothermia to loprazolam, Ro 17-1812, and to the partial
      inverse agonist Ro 15-4513, and exhibited marked hypothermia in response to the
      more efficacious benzodiazepine inverse agonist Ro 19-4603 and to FG 7142 and
      DMCM. Flumazenil did not alter body temperature. DBA/2 mice were also more
      sensitive to the convulsant activity of inverse agonists than TO mice. CBA/cA
      mice exhibited enhanced sensitivity to the convulsant, but not the hypothermic,
      effects of Ro 19-4603, showing dissociation of these responses. The mechanisms
      underlying the genetic differences in sensitivity of mice to the hypothermic and
      convulsant action of the different ligands are unknown and warrant further
      investigation.

PMID- 1365637
TI  - Antidepressant-like effect of neurotensin administered in the ventral tegmental
      area in the forced swimming test.
AB  - Locomotor activity and behaviour in the forced swimming test were examined in
      rats which had received neurotensin (0.5-5.0 micrograms) in the ventral tegmental
      area. Doses of 5 micrograms neurotensin but not lower increased the locomotor
      activity for at least 2 h. At 0.5 and 1.0 microgram neurotensin significantly
      increased the time the animals spent in struggling with no changes in general
      motor activity (swimming). The effect of 1.0 microgram neurotensin on struggling
      was completely antagonized by 0.5 microgram (-)-sulpiride administered in the
      posterior nucleus accumbens. The results suggest that activation of the
      mesolimbic dopamine system through administration of neurotensin in the ventral
      tegmental area produces antidepressant-like effects. The significance of these
      findings for a role of endogenous neurotensin in depression remains to be
      clarified.

PMID- 1365638
TI  - Effects of intra-hippocampal scopolamine injections in a repeated spatial
      acquisition task in the rat.
AB  - The involvement of hippocampal cholinergic synapses in spatial discrimination
      learning was evaluated by locally administering scopolamine into the hippocampus.
      Sixteen 16-month-old male Lewis rats received bilaterally implanted cannulae
      aimed at the dorsal part of the hippocampus. The rats were trained on a repeated
      acquisition test in the Morris water-escape task. In this procedure the invisible
      platform is randomly moved from day to day to one of four possible locations.
      Thus, the rat has to learn to localize the platform from day to day. On each day
      the rats received four pairs of trials. Scopolamine injections (35 micrograms in
      1 microliter per hippocampus) were given to one group (n = 8) on days 5 and 7. On
      days 6 and 8 all rats received saline injections. Place learning was retarded in
      the scopolamine-treated rats during the first swims of pairs of trials. During
      second swims the scopolamine-treated rats showed a general performance deficit,
      indicating that first and second swims were differentially affected. The data
      support the hypothesis that cholinergic neurotransmission in the dorsal
      hippocampus is involved in spatial learning processes.

PMID- 1365635
TI  - Peripheral modulation of learning and memory: enkephalins as a model system.
AB  - Extensive research on the effects of enkephalins on conditioning is reviewed and
      used as the basis for a model of peripheral modulation of learning and memory. An
      overall theme emphasized throughout our discussion is that these peptides can
      influence the strength with which a memory is acquired and stored by acting
      outside the blood-brain barrier. This assertion is supported by research on the
      behavioral effects of systemically administered enkephalins and opioid
      antagonists, the rapid hydrolysis of circulating enkephalins in vivo, and the
      limited ability of these peptides to penetrate the blood-brain barrier. A
      consideration of the extensive distribution of enkephalins throughout peripheral
      autonomic systems leads to the proposal that enkephalins may act to modulate
      learning and memory by altering peripheral autonomic function; autonomic
      afferents may then communicate with the memory trace in the CNS through a central
      modulatory pathway outlined herein. Evidence that some stressful experiences may
      lead to increases in circulating enkephalins also is discussed. The sites of
      action of these circulating enkephalins may involve peripheral autonomic sites,
      or additionally may involve the circumventricular organs. As a further regulatory
      mechanism, circulating enkephalin levels may be controlled by experience
      dependent alterations of the activity of enzyme systems that participate in their
      breakdown. Finally, it is emphasized that the mechanisms of enkephalin action
      postulated herein may be applicable to the actions of other peripheral hormones,
      peptides, and neurotransmitters that participate in the modulation of learning
      and memory storage processes.

PMID- 1365639
TI  - Hypouricemic effect of zuclopenthixol: a potential marker of drug compliance?
AB  - Twelve newly-admitted psychotic patients were treated with clinical doses of
      zuclopenthixol (ZPT). Plasma uric acid (PUA) was measured before and during
      treatment. ZPT reduced PUA in all the patients by an average of 29.6% (P <
      0.0001). PUA levels during treatment correlated with those obtained before
      treatment (R = 0.871, P < 0.0002). PUA returned to initial levels on
      discontinuation of treatment. Uric acid excretion increased during treatment. It
      is concluded that ZPT is a potent uricosuric agent, capable of producing
      persistent hypouricemia while administered. Such hypouricemia might be a useful
      indicator of drug compliance.

PMID- 1365640
TI  - Anxiogenic drugs beta-CCE and FG 7142 increase extracellular dopamine levels in
      nucleus accumbens.
AB  - Two experiments were conducted to study the effects of anxiogenic drugs on
      dopamine release and metabolism in nucleus accumbens. Microdialysis probes were
      implanted into the nucleus accumbens, and rats were tested the day after
      implantation. In the first experiment, groups of rats received injections of
      saline, 1.25 or 2.5 mg/kg beta-CCE. In the second experiment, groups of rats
      received injections of saline, 10.0, 20.0 or 30.0 mg/kg FG-7142. Both drugs
      produced significant increases in dopamine release and metabolism in nucleus
      accumbens. Neither drug had significant effects on locomotor activity. These
      experiments indicate that exposure to anxiogenic drugs increases accumbens
      dopamine activity, an effect that is consistent with other studies showing that
      the mesolimbic dopamine system is responsive to stressful stimuli. In addition,
      these results demonstrate that drug-induced increases in accumbens dopamine
      release are not unique to drugs of abuse.

PMID- 1365641
TI  - Monocyte chemoattractant protein-1 (MCP-1) expression in human articular
      cartilage. Induction by peptide regulatory factors and differential effects of
      dexamethasone and retinoic acid.
AB  - Monocyte influx and activation in synovial joints are important in the
      pathogenesis of both degenerative and inflammatory arthropathies. In this study,
      we demonstrate the potential of articular cartilage to directly modulate these
      events. IL-1-stimulated human articular chondrocytes transcribed 0.7-kb monocyte
      chemoattractant protein-1 (MCP-1) mRNA. In situ hybridization of cartilage organ
      cultures revealed MCP-1 transcripts in chondrocytes in the superficial tangential
      zone within 2 h of stimulation with IL-1. Chondrocytes in deeper layers responded
      by 4 h and reached maximum MCP-1 mRNA levels by 8-12 h. IL-1-stimulated cartilage
      organ and chondrocyte monolayer cultures released functional monocyte chemotactic
      activity. This was neutralized by a monoclonal antibody specific for MCP-1, and
      was associated with the synthesis and secretion of immunoreactive 13-kD and 15-kD
      isoforms of MCP-1. Regulators and signal transduction pathways involved with the
      expression of the MCP-1 gene in chondrocytes were analyzed. Steady-state mRNA
      levels were increased by the known chondrocyte activators IL-1, tumor necrosis
      factor alpha, LPS, platelet-derived growth factor, and transforming growth factor
      beta. In addition, leukemia inhibitory factor induced MCP-1 gene expression and
      protein synthesis, identifying this cytokine as a new regulator of chondrocyte
      function. Dexamethasone blunted the induction of MCP-1 gene expression by IL-1
      and by activators of protein kinase A as well as protein kinase C signal
      transduction pathways. In contrast, retinoic acid strongly increased phorbol
      myristate acetate-induced MCP-1 expression and potentiated the effects of IL-1
      and LPS. In conclusion, chondrocytes express MCP-1 in response to factors that
      are present in cartilage or synovium. This provides a mechanism by which
      cartilage can play an active role in the initiation and progression of arthritis.

PMID- 1365642
TI  - Differential development of acute tolerance to the motor impairment and
      anticonvulsant effects of ethanol.
AB  - The development of acute tolerance to the motor impairment and anticonvulsant
      effects of ethanol was examined. Acute tolerance to the motor impairment effect
      of ethanol was shown by a decrease in the degree of intoxication, as measured on
      the moving belt task, at higher blood ethanol levels ranging from 206 to 256
      mg/dl. There was no evidence of acute tolerance to the anticonvulsant effect of
      ethanol in rats tested over the same time period. These results indicate that,
      like chronic tolerance, acute tolerance to ethanol develops at different rates
      for different effects of the drug. The fact that chronic tolerance to the
      anticonvulsant effect of ethanol has been well documented raises doubts about the
      assumption that similar physiological changes underlie acute and chronic
      tolerance to a drug effect, and support the idea that the relationship between
      acute and chronic tolerance is more complex than previously thought.

PMID- 1365643
TI  - Tolerance to ethanol's effects on operant performance in rats: role of number and
      pattern of intoxicated practice opportunities.
AB  - Acquisition and retention of tolerance to ethanol's rate-decreasing effects on
      operant performance were examined in rats which received a 52-day regimen of
      ethanol or saline injections prior to and/or after each daily session. Eight
      groups of rats differed on: (a) number of days with intoxicated practice (pre
      session ethanol); (b) intermittent (spaced) or daily (massed) intoxicated
      practice; and (c) post-session ethanol or saline on non-intoxicated practice
      days. Massed practice groups were given their presession saline days prior to
      their pre-session ethanol days. Ethanol dose-effect tests were given prior to,
      during, and after the chronic injection regimen. Under both spaced and massed
      practice conditions, the magnitude of tolerance developed increased directly with
      the number of pre-session ethanol days, even when absolute ethanol exposure was
      constant. No group showed complete tolerance loss. The post-session ethanol
      supplements (a) facilitated tolerance development in spaced practice groups and
      tolerance loss in massed practice groups, (b) blocked ethanol's low dose rate
      increasing effects, and (c) produced an acute withdrawal-like performance
      disruption the next day. The results suggest that both intoxicated practice and
      practice during acute ethanol withdrawal influence the acquisition and retention
      of compensatory behaviors during ethanol tolerance development.

PMID- 1365645
TI  - Effects of caffeine, time of day and user history on study-related performance.
AB  - The individual and interactive effects of caffeine, time of day and history of
      caffeine consumption on several study-related tasks were investigated in 25
      subjects (6 males, 19 females). Performance was measured on short term memory
      (STM), mental arithmetic (MA), reading comprehension, serial search (SS) and
      verbal reasoning (VR). Subjects attended eight experimental sessions, at four
      times of day (0100, 0700, 1300 and 1900 hours), after ingesting caffeine (4
      mg/kg) or placebo. Subjects were assigned to a low, moderate or high user group
      on the basis of a caffeine consumption questionnaire. Reading comprehension was
      affected by time of day, while caffeine improved performance on all mental speed
      related tasks. High caffeine users performed more poorly than other groups on the
      verbal reasoning task. Several interactions between the three independent
      variables were observed on a number of tasks, supporting the contention that
      different processes underlying various types of cognitive performance are
      differentially, and often jointly, affected by caffeine, time of day and user
      history. Implications of caffeine usage on academic performance were discussed.

PMID- 1365644
TI  - Psychopharmacological properties of calcium channel inhibitors.
AB  - The previous decade has witnessed a major expansion of knowledge of the role
      played by voltage-sensitive calcium channels in the function of the central
      nervous system. Significant progress in the field has been made possible with the
      broadening use of organic calcium channel inhibitors (CCIs, Ca2+ antagonists),
      until recently considered almost exclusively as peripherally active antianginal
      and antiarrhythmic drugs. CCIs, however, do penetrate the blood-brain barrier
      from the periphery. Autoradiographic studies have established a highly
      heterogeneous distribution of CCI recognition sites within the brain. The
      existing evidence suggests that CCIs have marked psychotropic properties. The
      profile of their central activity is unique and spans a wide range of effects.
      Nevertheless, question regarding potentially confounding potent peripheral
      effects of these drugs remain. This paper reviews the psychopharmacology of CCIs,
      concentrating on preclinical data, but including supportive clinical and
      biochemical evidence as well. It focuses on these drugs' antidepressant,
      antidopaminergic (neuroleptic-like), anxiolytic and anticonvulsant effects. CCIs
      may also modify the reinforcing properties of some addictive drugs.

PMID- 1365646
TI  - Comparative effects of alpha-2 receptor agents and THA on the performance of
      adult and aged rats in the delayed non-matching to position task.
AB  - The present study investigated the effects of dexmedetomidine (an alpha-2
      adrenoceptor agonist), atipamezole (an alpha-2 adrenoceptor antagonist) and
      tacrine (an inhibitor of acetylcholinesterase) on the performance of adult and
      aged rats in a delayed non-matching to position task assessing spatial short-term
      memory. Most of the aged rats were impaired in the pretraining phases and in the
      acquisition of the non-delayed version of the task. After a substantial training
      period of the delayed version of the task, both adult and aged rats reached their
      asymptotic level of performance. Both adult and aged rats showed a decline in the
      percent correct responses at the longest delays in this task, and a delay
      independent decrease in the percent correct responses across the delays (0-30 s)
      was found in the group of aged rats (25-month-old) as compared to the adults (10
      month-old). Dexmedetomidine (0.3, 1.0 or 3.0 micrograms/kg), atipamezole (0.03,
      0.3 or 3.0 mg/kg) and tacrine (1.0 or 3.0 mg/kg) did not increase the percent
      correct responses in adult or aged rats. The highest doses of dexmedetomidine and
      tacrine decreased behavioural activity of rats during this short-term memory
      testing. Atipamezole (0.03 mg/kg) increased behavioural activity of rats. The
      results suggest that acute, systemic administrations of alpha-2 drugs or an
      anticholinesterase do not improve short-term memory in rats.

PMID- 1365648
TI  - Effects of methylphenidate on response rate and measures of motor performance and
      reinforcement efficacy.
AB  - This experiment evaluated the effects of methylphenidate on reinforced responding
      in rats. In each session the subjects (rats) earned reinforcement on seven
      different variable-interval reinforcement schedules. The average intervals varied
      from 108 to 3 s and provided reinforcement rates ranging from about 30 to 1100/h.
      Response rate was a negatively accelerated function of reinforcement rate. Low
      doses of methylphenidate (1.0 and 2.0 mg/kg) increased responding maintained by
      the four leanest schedules, but had little effect on responding maintained by the
      three densest schedules. In contrast, an 8.0 mg/kg dose increased responding
      maintained by the three densest schedules and slightly decreased responding
      maintained by leaner schedules. A quantitative model of reinforced responding,
      referred to as the matching law or response strength equation, was fitted to the
      data. This equation has two parameters. On the basis of previous experiments, one
      was used to measure changes in reinforcement efficacy and the other was used to
      measure changes in motor performance. The 1.0 and 2.0 mg/kg doses changed the
      reinforcement parameter in the same way as did increases in deprivation and
      reward magnitude. The 8.0 mg/kg dose changed the motor parameter in the same was
      as did decreases in lever weight. It was concluded that methylphenidate increases
      reinforcement efficacy, and that the highest dose changed the topography of
      responding. The results are discussed in terms of the response strength equation,
      the rate dependency principle, and the question of how to interpret changes in
      reinforcement efficacy and motor performance.

PMID- 1365647
TI  - Effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) after repeated
      administration on a conditioned avoidance response (CAR) in the rat.
AB  - 8-OH-DPAT, a selective 5-HT1A agonist, has variously been found to impair, have
      no effect on or enhance the conditioned avoidance response (CAR). Procedural
      differences may account for the difference in results. In the first experiment in
      the present study rats were trained in the two-way active avoidance procedure to
      a criterion of 65% avoidance. Separate groups of rats were treated with 0.01, 0.1
      or 1.0 mg/kg 8-OH-DPAT SC once per day for 14 days. The rats were tested in the
      CAR each day 5 min after treatment, using a 10 s light and tone conditioned
      stimulus and five 0.2 mA/0.5 s electric shocks. On the first day the doses of 0.1
      and 1.0 mg/kg impaired avoidance, but by the end of training these two doses
      increased avoidance. This change in effect was accompanied by a 15-fold increase
      in the number of trials in which the subject crossed during a 10 s period of the
      ITI, which in turn led to a significant impairment in the discrimination ratio.
      The results of this experiment show that with repeated treatment 8-OH-DPAT
      changes from being antipsychotic like to being stimulant-like. The latter effect
      produces an improvement in avoidance, probably due to a non-specific increase in
      activity. In the second experiment, the rats were divided into groups based upon
      the undrugged performance. The avoidance-enhancing effect of 8-OH-DPAT was
      greater in magnitude in a group of poor performers, but was qualitatively similar
      in good performers. In the second stage of the experiment, gradual withdrawal
      from the drug was compared with sudden withdrawal. In the gradual withdrawal
      group, a reduction in the dose from 0.085 mg/kg to 0.01 mg/kg resulted in a
      gradual disappearance of the enhanced activity. There was an almost linear
      relationship between performance and the log dose of the drug, suggesting that
      the increase in activity seen after repeated administration of 8-OH-DPAT is
      directly related to the acute level of drug administered. This effect was evident
      in both good and poor performers. On the basis of these results it is suggested
      that many, but not all, antidepressant-like effects of 8-OH-DPAT may result from
      changes in activity.

PMID- 1365649
TI  - Effect of acute and chronic benzodiazepines on plasma GABA in anxious patients
      and controls.
AB  - The acute effects of diazepam on plasma GABA were determined in 18 patients with
      panic disorder, 13 patients with generalized anxiety disorder and 20 healthy
      controls. All subjects were benzodiazepine-naive. Four logarithmically increasing
      doses of diazepam/placebo were administered intravenously at 15-min intervals on
      2 separate days. Plasma GABA was measured at baseline and 3 min after the highest
      dose of diazepam/placebo. There was an overall decrease in plasma GABA that was
      significantly greater following diazepam compared with placebo, but no group
      differences in response. In a separate group of 18 panic disorder patients
      receiving chronic benzodiazepine treatment with alprazolam, the same diazepam
      infusion procedure (no placebo day) produced decreases in plasma GABA similar to
      those seen in the untreated panic disorder patients. The clinical and physiologic
      implications of these findings are discussed.

PMID- 1365651
TI  - Interactions of the beta carboline abecarnil with the high pressure neurological
      syndrome in a primate model.
AB  - The neurophysiological interactions between the high pressure neurological
      syndrome (HPNS) and a new beta carboline, abecarnil, were studied in the non
      human primate Papio anubis. Abecarnil is a partial agonist at the benzodiazepine
      site on the GABA/benzodiazepine receptor. Six animals were exposed on two
      occasions to pressures of 91 ATA in an environment of helium and oxygen. One
      exposure was pretreated with a total dose of abecarnil 1.0 mg/kg, the other with
      an equivalent volume of vehicle. Treatment with abecarnil prevented the severe
      signs of HPNS occurring between 51 and 91 ATA. Onset pressures of the various
      signs were unaffected. Some signs, e.g. myoclonus, became more frequent when
      abecarnil was used. A residual protective effect of abecarnil was present 4 weeks
      after the dose was given, active at pressures less than 71 ATA. Changes with
      pressure in the EEG were recorded primarily from the frontal cortex, but were
      also present in the parietal and occipital areas of the left cortex. Amplitude
      and frequency spectra were calculated and changes with pressure in the four
      conventional wavebands, plus two others, analysed. The most striking change was
      the prevention by abecarnil of the pressure-induced 100% increase in alpha wave
      amplitude in the frontal region. It is concluded that modulation of GABA
      transmission is important in controlling the expression of HPNS.

PMID- 1365650
TI  - Roles of delta and mu opioid receptors in mediating the effects of enkephalins on
      avoidance conditioning.
AB  - The effects on one-way active avoidance conditioning of pre-training, systemic
      administration of the selective mu-receptor agonist [D-Ala2,N-Me-Phe4, Gly
      ol]enkephalin (DAGO), and the selective mu-receptor antagonist (D-Phe-Cys-Tyr-D
      Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), were determined in Swiss-Webster mice. A low dose
      of DAGO (0.92 micrograms/kg) moderately enhanced avoidance acquisition, whereas a
      100 micrograms/kg dose of CTOP more dramatically impaired acquisition. However,
      the avoidance-enhancing dose of DAGO significantly increased locomotor activity
      as measured in a separate group of mice in the avoidance chamber, and the
      avoidance-impairing dose of CTOP significantly decreased activity. Under these
      same training conditions, earlier studies (Schulteis et al. 1988; Schulteis and
      Martinez 1990) demonstrated that enkephalins impaired avoidance learning, and
      selective delta-receptor antagonists such as ICI 174,864 enhanced learning; in
      contrast to the present study, both of these effects were dissociated from
      performance effects such as alterations in locomotor activity. Taken together,
      the results suggested that the effects of enkephalins were mediated by the delta
      , but not mu-, class of opioid receptor.

PMID- 1365652
TI  - Effect of number of conditioning trials on the development of associative
      tolerance to morphine.
AB  - The acquisition of associative tolerance to the analgesic effects of morphine was
      investigated by giving independent groups of rats 1, 3, 5, 8, 14, 20, or 30
      administrations of drug either explicitly paired or unpaired with a distinctive
      context. Tolerance, assessed on a tail-flick device using dose-response curve
      (DRC) methodology, developed more rapidly and reached greater magnitude when
      morphine and the distinctive context were explicitly paired rather than
      explicitly unpaired. Tolerance magnitude in both conditions reached a maximum at
      eight conditioning sessions. It is argued that the tolerance found in both
      treatment groups was associatively controlled. The function of handling and
      injection cues as conditioned stimuli, and the deleterious effects of latent
      inhibition and partial reinforcement on conditioned excitation and conditioned
      inhibition are discussed.

PMID- 1365653
TI  - Corticotropin-releasing factor modulates dietary preference in nutritionally and
      physically stressed rats.
AB  - In order to evaluate the action of central nervous system Corticotropin-Releasing
      Factor (CRF) in the control of feeding behavior the present studies employed a
      dietary self-selection task sensitive both to overall appetite as well as
      preferential intake of familiar versus unfamiliar foods. Prior to the diet
      selection test, one group of nutritionally stressed animals was fed a protein
      deficient diet in order to increase the preference for unfamiliar foods relative
      to nutritionally replete subjects. Both CRF (0.05 and 0.5 micrograms ICV) and
      physical restraint (30 min) attenuated selectively the consumption of a novel
      food choice by deficient animals without affecting concurrent intake of familiar
      food. Further, CRF administration did not alter water intake or consumption of
      either diet by the replete control group suggesting that the peptide produced a
      stress dependent, enhanced response to novelty without a general effect on
      appetite. The CRF antagonist, alpha-helical CRF9-41 (1, 5 and 25 micrograms ICV),
      increased familiar diet consumption in nutritionally deficient subjects without
      affecting the self-selection pattern or replete controls. Chlordiazepoxide (5
      mg/kg) also increased selectively the intake of familiar food suggesting that
      this action is the anxiolytic complement of the effect of stress in this
      paradigm. The CRF antagonist (5 and 25 micrograms) reversed the anorexia produced
      by CRF (0.5 micrograms) as well as that induced by restraint stress. These
      results favor a direct role for endogenous CRF systems in coordinating the
      behavioral responses to dietary stress.

PMID- 1365654
TI  - Contribution of associative and nonassociative processes to the development of
      morphine tolerance.
AB  - The contribution of associative and nonassociative processes to the development
      of tolerance to the analgesic effects of morphine in rats was investigated in two
      experiments. Associative contingencies were manipulated by administering a series
      of moderately high morphine doses (20 mg/kg) either explicitly paired or
      explicitly unpaired with a distinctive context. During distinctive context
      exposures, animals were placed for 60 min in plastic boxes located in a room
      adjacent to the colony room. The distinctiveness of this environment was enhanced
      by the presence of white noise and a pine scent. Nonassociative processes were
      manipulated by administering the morphine at either a very short (6 h) or
      relatively long (96 h) interdose-interval (IDI). Analgesia was measured on a tail
      flick test. At the 96 h IDI, tolerance, as indexed by shifts in dose-response
      curves, was controlled primarily by associative processes. Associative control
      over tolerance at the long IDI was evident at an immediate test (experiment 1)
      and was retained for a 30 day interval (experiment 2). In contrast, tolerance
      that developed at the 6 h IDI was not influenced by associative contingencies at
      the immediate test (experiment 1) and showed no retention over a 30 day interval
      (experiment 2). These data suggest that tolerance that developed at the short IDI
      was nonassociative. Overall, the results indicate that conditions conductive to
      the development of non-associative tolerance disrupt the acquisition of
      associative tolerance. Hypotheses regarding the absence of associative effects at
      the short IDI are reviewed. Methodological implications of these results for
      evaluations of associative and nonassociative morphine tolerance are also
      discussed.

PMID- 1365655
TI  - Neonatal administration of a GABA-T inhibitor alters central GABAA receptor
      mechanisms and alcohol drinking in adult rats.
AB  - Long-term effects of chronic treatment with a GABA-T (GABA-transaminase)
      inhibitor, ethanolamine O-sulphate (EOS) (200 mg/kg/day for the postnatal days 3
      21) on the binding parameters of GABAA receptors, hypothalamic monoamines and
      subsequent behavior were studied in Wistar rats. At the age of 1 month, EOS
      treated rats showed reduced activity in the open-field and, at the age of 4
      months, their voluntary alcohol consumption was increased. No changes were seen
      in Porsolt's swim test or in the plus-maze test. Weight gain was significantly
      retarded in EOS-treated rats. Maximal stimulation of [3H] flunitrazepam binding
      by GABA was decreased in the cerebral cortex and the EC50-value for the GABA
      stimulation increased in the hippocampus in the EOS rats at the age of 4 months.
      EOS treatment did not alter the cerebellar diazepam sensitive and insensitive
      binding components of the imidazobenzodiazepine [3H]Ro 15-4513. No changes were
      observed in the hypothalamic monoamine concentrations. The results are in
      agreement with the idea that GABA-T inhibitor treatment permanently alters GABAA
      mechanisms. Moreover, altering the CNS GABA level during development increases
      adult alcohol intake in rat.

PMID- 1365656
TI  - Effects of physostigmine on stimulus encoding in a memory-scanning task.
AB  - Previous studies of the effects of physostigmine on memory have involved other
      drugs, a memory that has already been impaired, or both, often with contradictory
      results. Also, traditional memory tests do not differentiate memory from other
      task components such as perception and response, and drug effects on these could
      be mistaken for effects on memory. The present study was designed to investigate
      the effects of physostigmine alone on normal memory using Sternberg's additive
      factor, memory-scanning task, with additional variables to isolate effects on
      stimulus encoding and response stages. Sixteen volunteers participated, the
      design was between-groups, and physostigmine or normal saline was given, double
      blind, by intravenous infusion for 70 min. The drug had no effect on the memory
      component of the task, but significantly improved stimulus encoding (P < 0.001).
      Thus, it is possible that physostigmine improves performance on memory tests by
      improving perception as well as, or instead of, memory.

PMID- 1365658
TI  - Dissociation between the effects of benzodiazepine receptor agonists on
      behavioral vigilance and responsitivity.
AB  - The effects of benzodiazepine receptor (BZR) full agonists chlordiazepoxide and
      midazolam, and the partial agonist beta-carboline ZK 91,296 on the rat's
      performance in a simple reaction time paradigm were examined. This task required
      the animals to respond to a rarely and unpredictably occurring brief (50 ms)
      visual stimulus. Non-parametric measures of signal sensitivity and response bias
      derived from signal-detection theory were used as a basis for the dissociation
      between the effects of these drugs on attentional abilities and general
      responsivity. The dose-dependent effects of midazolam (0.1-3.13 mg/kg) on signal
      sensitivity and general responsivity occurred in parallel. In contrast, the
      effects of chlordiazepoxide (1.56-12.5 mg/kg) on signal sensitivity were largely
      independent from effects on response bias. The partial agonist ZK 91,296 (0.39-25
      mg/kg) in general had little effect on performance. The effects of the highest
      doses of chlordiazepoxide and midazolam were reversed by the co-administration of
      the BZR antagonist Ro15-1788 (15 mg/kg). Additionally, extension of the stimulus
      presentation time to 500 ms decreased the magnitude of the effect of
      chlordiazepoxide on signal sensitivity. These results support the hypothesis that
      BZR agonist-induced disruption of attentional abilities is not necessarily
      confounded by effects on general responsivity or sedation, and thus may represent
      a discrete pharmacological property of BZR-agonists.

PMID- 1365657
TI  - A comparison of trazodone and fluoxetine: implications for a serotonergic
      mechanism of antidepressant action.
AB  - Trazodone is an atypical antidepressant drug that is commonly referred to as a
      serotonin (5-hydroxytryptamine; 5-HT) uptake inhibitor. However, the most potent
      pharmacological effect of trazodone appears to be antagonist action at 5-HT2/1C
      receptors. This is in contrast to fluoxetine, for which inhibition of 5-HT uptake
      is the most potent pharmacological action. The effects of trazodone and
      fluoxetine on several antidepressant drug screens are mediated by antagonist
      action at 5-HT2 receptors and inhibition of 5-HT uptake, respectively. While
      fluoxetine is an effective agent for the treatment of major depression, obsessive
      compulsive disorder (OCD) and panic disorder, trazodone does not appear to be
      effective in the treatment of OCD and panic disorder. In addition, trazodone and
      fluoxetine differ in humans with respect to their effects on sleep and weight.
      Taken together, the preclinical and clinical data suggest that trazodone acts as
      an antidepressant via antagonist action at 5-HT2/1C receptors, while fluoxetine
      likely acts as an antidepressant via inhibition of 5-HT uptake.

PMID- 1365659
TI  - Effect of 5-HT agonists on rats fed single diets with varying proportions of
      carbohydrate and protein.
AB  - Low doses of 5-HT agonists have been shown to selectively suppress carbohydrate
      intake in rats given dietary choices. To investigate further the relationship
      between dietary macronutrient composition and 5-HT-induced anorexia, the present
      study examined the effects of three 5-HT agonists on rats fed single isocaloric
      diets containing varying proportions of carbohydrate (CHO) and protein (PRO).
      Rats were habituated to eat one of the three diets (73.5% CHO--10% PRO, 58.5% CHO
      -25% PRO or 43.5% CHO--40% PRO) during the dark period (1900-0700 h). Saline or 5
      HT agonists (fluoxetine, RU 24969 and dexfenfluramine) were administered
      intraperitoneally at 1845 hours, 15 min prior to food access. At the doses used,
      food intake was significantly affected only during the first hour of eating. All
      5-HT agonists caused dose-dependent decreases in food intake (P < 0.01). The
      magnitude of decrease, however, was significantly influenced by diet composition.
      Reduction in intake was greatest in rats fed the 73.5% CHO--10% PRO diet. Thus,
      rats chronically fed a diet high in carbohydrate content were more sensitive to
      the anorectic effect of 5-HT agonists than rats fed diets containing moderate to
      low levels of carbohydrate.

PMID- 1365660
TI  - Context-drug pairings enhance tolerance to ethanol-induced disruption of operant
      responding.
AB  - Much of the research implicating learning in the development of tolerance to
      ethanol-induced impairment has used an experimental design in which different
      groups receive drug either before or after an opportunity to perform an
      instrumental or operant task. The stronger tolerance observed in subjects who
      perform while intoxicated is most often attributed to the reinforced practice of
      a learned compensatory response. Using an experimental procedure modeled after
      Chen (1979), the present study examined an alternative theoretical basis for
      tolerance in the before-versus-after design. Specifically, the effects of
      Pavlovian context-drug pairings were assessed under circumstances that precluded
      reinforced practice of the operant response. Three groups of food-deprived rats
      were initially trained to barpress for sucrose on an FR15 schedule. After 30
      sessions, the bar was retracted and the dipper was covered for a 3-day tolerance
      acquisition phase. During this phase, each group received an IP injection 15 min
      before and 45 min after each session. The Paired group received ethanol (1.2
      g/kg) before and saline after the session, thus pairing ethanol with cues of the
      test chamber. The Unpaired group received saline before and ethanol after the
      session, while the No-Drug group always received saline. During a final test
      phase, all groups received ethanol (1.5 g/kg) before access to sucrose on the FR
      schedule. The Paired group completed the first FR15 sequence more rapidly than
      either control group, indicating that context-ethanol pairings enhanced tolerance
      to the drug's disruptive effect on the initiation of operant responding.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1365661
TI  - Attenuation of muscarinic receptor blockade-induced impairment of spatial delayed
      alternation performance by the triazole MDL 26,479.
AB  - The interactions between the effects of MDL 26,479 (0.1, 0.39, 1.56, 6.25 mg/kg;
      IP) and the muscarinic antagonist scopolamine (0.03, 0.1 mg/kg; IP) on the
      performance of rats in a delayed alternation task (retention intervals: 2, 4, 8,
      16, 32 s) were examined. Scopolamine dose-dependently reduced the relative number
      of correct responses and interacted with the effects of the length of retention
      intervals. MDL 26,479 did not affect correct responding but attenuated the
      behavioral impairments produced by scopolamine. Although this task did not
      explicitly exclude the possibility that the animals acquired mediational response
      strategies, and although the effects of scopolamine appeared to interfere with
      the execution of these strategies, to a major extent, the attenuative effects of
      MDL 26,479 were not related to its effects on mediational strategies. Thus, it is
      concluded that administration of MDL 26,479 mainly resulted in a re-establishment
      of the animals' ability to memorize and/or to recall the information required to
      exert correct responses.

PMID- 1365662
TI  - Platelet adenylate cyclase activity in depression and after clomipramine and
      lithium treatment: relation to serotonergic function.
AB  - Adenylate cyclase activity was measured in platelet membranes from 10 healthy
      controls, 12 depressed patients, and the same patients after treatment with
      clomipramine (CMI) followed by lithium carbonate (Li) supplementation, in an
      attempt to determine whether any evidence for an effect on the serotonergic
      system could be obtained in peripheral cells. There were no differences in basal,
      NaF-, PGE1-, or forskolin-stimulated activity either between the control subjects
      and depressed patients or between activities in the patients measured before
      treatment, after CMI, and after CMI+Li. The degree of inhibition of forskolin
      stimulated adenylate cyclase by 5-HT, an effect putatively mediated by a 5-HT1A
      like receptor, was not different in the depressed patients compared to controls
      or affected by CMI treatment, but was significantly reduced after Li
      supplementation.

PMID- 1365663
TI  - Clonidine but not nifedipine prevents the release of noradrenaline during
      naloxone-precipitated opiate withdrawal: an in vivo microdialysis study in the
      rat.
AB  - In this study we have examined whether the alpha 2-adrenoceptor agonist clonidine
      and the calcium channel antagonist nifedipine firstly inhibit the naloxone
      precipitated withdrawal syndrome in morphine-dependent rats and secondly reduce
      central noradrenaline release during withdrawal. We demonstrate that both
      clonidine (0.1 mg/kg) and nifedipine (10 mg/kg) attenuate the naloxone
      precipitated withdrawal syndrome. Using in vivo microdialysis, we demonstrate
      that following naloxone the release of noradrenaline, as measured by perfusates
      from hippocampus, increases 300% in morphine-dependent rats. However, whilst
      pretreatment with clonidine inhibited this increased noradrenaline release,
      nifedipine did not. These findings suggest that whilst the action of clonidine in
      attenuating the morphine withdrawal syndrome may be mediated by decreasing
      central noradrenaline release, this is not the mechanism by which nifedipine
      acts.

PMID- 1365664
TI  - Role of central ATP-sensitive potassium channels in the hyperthermic effect of
      morphine in mice.
AB  - Morphine (10 mg/kg, SC) in combination with ICV vehicle induced a significant
      hyperthermic effect at 120 min (peak time) after injection compared to ICV
      vehicle plus SC saline (control group). Glibenclamide (50 micrograms, ICV), a
      selective adenosine triphosphate-sensitive potassium (KATP) channel blocker, in
      combination with SC saline hardly affected the rectal temperature compared to the
      control group. ICV glibenclamide antagonized the hyperthermia induced by SC
      morphine in a dose-dependent manner. From these results, we demonstrated that
      KATP channels play an important role as modulators of the hyperthermic effect of
      mu agonists.

PMID- 1365665
TI  - Selective effects of the D1 dopamine receptor agonist, SKF 38393, on behavior
      maintained by cocaine injection in squirrel monkeys.
AB  - The effects of the dopamine receptor D1 partial agonist, SKF 38393, on behavior
      maintained by cocaine was assessed in squirrel monkeys (Saimiri sciureus). One
      group of subjects was trained to press a key under a fixed-ratio 30-response
      schedule of cocaine injection; when green stimulus lamps were illuminated each
      30th response produced an injection (17 micrograms/kg) followed by a 1-min period
      during which the lights were out and responses had no scheduled consequences.
      Another group of squirrel monkeys was trained under an identical schedule with
      food reinforcement. SKF 38393 produced dose-related decreases in rates of
      responding maintained by either cocaine injection or food presentation. Rates of
      responding maintained by cocaine were decreased to a greater extent than those
      maintained by food. The ED50 value for SKF 38393 for responding maintained by
      cocaine was 2.53 mg/kg (95% CL: 1.22-5.23), whereas that value was 15.63 mg/kg
      (95% CL: 2.83-86.33) for responding maintained by food. Rates of responding
      maintained by cocaine were an inverted-U-shaped function of dose. Pretreatment
      with 3.0 mg/kg SKF 38393 shifted the ascending limb of the cocaine dose-effect
      curve to the right. These findings suggest that indirect D1-receptor activation
      plays a role in the reinforcing effects of cocaine, and that drugs acting at D1
      receptors may show promise as therapeutic agents in the treatment of cocaine
      abuse.

PMID- 1365666
TI  - Cocaine decreases self-control in rats: a preliminary report.
AB  - Cocaine abuse is often associated with behavior that takes into account short
      term, but not long-term consequences. However, there has been no empirical
      research concerning the effects of cocaine on self-control (choice of a larger,
      more delayed reinforcer over a smaller, less delayed reinforcer). In the present
      research, when food-deprived rats repeatedly chose between a larger, more delayed
      food reinforcer and a smaller, less delayed food reinforcer, chronic
      intraperitoneal injections of 15 mg/kg cocaine (but not 10 mg/kg fluoxetine)
      decreased the rats' choices of the larger, more delayed reinforcer. Cocaine can
      decrease rats' self-control.

PMID- 1365667
TI  - Effects of chronic nicotine and haloperidol administration on muscarinic receptor
      mediated phosphoinositide turnover in rat brain slices.
AB  - Muscarinic receptor-mediated phosphoinositide (PI) turnover in rat brain slices
      was assessed after chronic administration of nicotine (12 mg/kg/day) or
      haloperidol decanoate (1.5 mg/kg/day), either alone or in combination, for 6
      weeks. Nicotine alone did not significantly alter carbachol-induced inositol
      monophosphate (IP1) accumulation in the frontal cortex, but did result in a
      significant increase in the hippocampus, and in a decrease in the striatum.
      Haloperidol alone attenuated carbachol-stimulated IP1 accumulation in all three
      brain regions. Chronic treatment with combined nicotine and haloperidol resulted
      in no significant change in carbachol-sensitive IP1 accumulation in either the
      frontal cortex or hippocampus but did result in a decrease in the striatum. The
      results suggest significant cross-talk between cholinergic and dopaminergic
      systems in affecting PI metabolism.

PMID- 1365668
TI  - Evidence that the large neutral amino acid L-valine decreases electrically-evoked
      release of 5-HT in rat hippocampus in vivo.
AB  - L-Valine competes with tryptophan for transport into the brain and has previously
      been shown to decrease brain 5-HT synthesis. In the present study, the effect of
      L-valine on electrically evoked hippocampal 5-HT release was determined in the
      anaesthetized rat using microdialysis. In control animals two electrical
      stimulations of the dorsal raphe nucleus 120 min apart (S1 and S2, respectively)
      released similar amounts of 5-HT. In contrast, in animals which received L-valine
      (200 mg/kg) between stimulations, S2 released a significantly smaller amount of 5
      HT than did S1, although basal 5-HT release was unchanged. The data demonstrate
      that L-valine decreases the electrically-evoked release of 5-HT in hippocampus in
      vivo.

PMID- 1365669
TI  - Dose-response studies with co-dergocrine mesylate under hypoxia utilizing EEG
      mapping and psychometry.
AB  - In a double-blind, placebo-controlled trial, human brain function and mental
      performance were studied under two different degrees of hypoxia after
      administration of two different doses (6 mg and 9 mg) of co-dergocrine mesylate
      (CDM) utilizing blood gas analysis, EEG mapping and psychometry. Hypoxic
      hypoxidosis (i.e. impairment of cerebral metabolism due to hypoxia) was
      experimentally induced by a fixed gas combination of 9.8% oxygen (O2) and 90.2%
      nitrogen (N2) (found in 6000 m altitude), and of 8.6% O2, 91.4% N2 (found in 7000
      m altitude), which was inhaled for 23 min under normobaric conditions by 18
      healthy volunteers. They received randomized after an adaptation session placebo,
      6 mg and 9 mg co-dergocrine mesylate (CDM). Evaluation of blood gases, brain
      mapping and psychometry was carried out at 0, 2, 4, 6, 8 h after oral drug
      administration. Blood gas analysis demonstrated a drop in PO2 to 42 and 32 mm Hg
      23 min after inhalation of the 9.8% and 8.6% gas mixture, respectively, PCO2
      decreased to 32 and 31 mm Hg, pH increased to 7.46 and 7.47 and base excess
      increased to 0.50 and 0.90 nmol/l, respectively. EEG mapping demonstrated an
      increase in delta and decrease of alpha power and a slowing of the centroid over
      almost the whole brain. 6 mg and slightly less so 9 mg CDM attenuated this
      deterioration of vigilance (i.e. dynamic state of the neuronal network
      determining adaptive behavior). At the behavioral level, moderate hypoxia induced
      a deterioration of noopsychic performance, which was mitigated by 6 mg, but not
      by 9 mg CDM. A deepening of the hypoxia resulted in a loss of these brain
      protective effects of both doses. Decrement of the thymopsyche increased after
      both doses in the moderate hypoxic condition, while under marked hypoxia 6 mg CDM
      attenuated and 9 mg aggravated this deterioration. Time-wise, brain protective
      effects reached the level of statistical difference between the 2nd and the 6th
      hour. Somatic complaints like feeling dazed, giddiness and headache were
      mitigated dose dependently by CDM in the moderate, but not in the marked hypoxic
      hypoxidosis.

PMID- 1365670
TI  - Parametric and pharmacological analyses of the enhanced grooming response
      elicited by the D1 dopamine receptor agonist SKF 38393 in the rat.
AB  - The present report investigated several parametric and pharmacological aspects of
      the enhanced self-grooming behavior of rats following systemic administration of
      the selective D1 dopamine (DA) receptor agonist SKF 38393. The amount of time
      that rats spent grooming themselves was measured continuously for 30 min
      following drug administration to provide a quantitative measure of the drug
      induced behavior. SKF 38393 increased the amount of grooming in a dose-dependent
      manner (0.5-16 mg/kg, SC). The onset of this effect required at least 5 min and
      it persisted for at least 60 min. The ability of SKF 38393 to enhance grooming
      was shared by R-SKF 38393, but not S-SKF 38393, consistent with the affinities of
      these enantiomers for the D1 DA receptor. Unlike SKF 38393, the peripheral D1
      agonist fenoldopam (SKF82526) failed to cause an increased grooming response,
      suggesting a central site of action for elicitation of this behavior. The SKF
      38393-induced increase in grooming was competitively antagonized by the D1
      selective antagonist SCH 23390 (0.5 mg/kg, SC). Although the D2 DA receptor
      selective antagonist eticlopride reduced SKF 38393-elicited grooming, this
      antagonism appeared to be of a physiological rather than pharmacological nature.
      When eticlopride was coadministered with the non-selective (mixed) D1/D2 agonist
      apomorphine, an increase in grooming behavior similar to that produced by SKF
      38393 was observed. Inactivation of D1 and D2 DA receptors produced by
      pretreatment with the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2
      dihydroquinoline (EEDQ), at a dose which reduces D1 and D2 receptor density by >
      or = 50% (8.0 mg/kg, IP), reduced SKF 38393-induced grooming by approximately
      50%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1365671
TI  - Motor activity following the administration of selective D-1 and D-2 dopaminergic
      drugs to MPTP-treated common marmosets.
AB  - The ability of selective D-1 agonist and antagonist drugs to alter motor deficits
      and locomotor activity was studied in MPTP-treated common marmosets. Both the D-2
      agonist quinpirole and the mixed D-1/D-2 agonist apomorphine reversed the motor
      impairments and induced locomotor activity. The D-1 antagonist SCH 23390 and the
      D-2 antagonist raclopride given alone further reduced motor function in MPTP
      treated animals. The actions of quinpirole were potently and completely inhibited
      by raclopride but only partially and inconsistently by SCH 23390. In contrast,
      the effects of apomorphine were markedly but incompletely inhibited by both
      raclopride and SCH 23390. The D-1 agonist SKF 38393 alone caused a dose related
      reduction in motor activity. SKF 38393 weakly and partially inhibited the
      improvements in motor function produced by quinpirole but had a more pronounced
      effect on apomorphine induced motor activity. The induction of motor activity in
      MPTP treated common marmosets may separately involve both D-1 and D-2 receptors.
      Comparison with our previous data on the effect of the same drugs in normal
      common marmosets provides some evidence for a breakdown of linkage between D-1
      and D-2 systems following MPTP treatment. The actions of SKF 38393 in MPTP
      treated common marmosets contrasts with its ability to induce behavioural
      activation and a facilitation of D-2 mediated behaviour in rodents. SKF 38393 may
      not be the compound with which to delineate the role of D-1 receptors in
      primates.

PMID- 1365672
TI  - Imipramine and 2-hydroxyimipramine: comparative cardiotoxicity and
      pharmacokinetics in swine.
AB  - The hemodynamic, cardiographic, and initial pharmacokinetic characteristics of
      the de novo administration of the 2-hydroxymetabolite (2-OH-IMI) of imipramine
      (IMI), compared with its parent was studied in a swine preparation. Cardiac
      output, arterial pressure, and the continuous electrocardiogram were assessed
      after the intravenous administration of the drug or its metabolite. Plasma,
      sampled over 120 min and CSF sampled at 60 min were analyzed by reverse phase
      HPLC with spectroflurometric detection. Equilibrium dialyses were performed on
      plasma sampled at 60 min. 2-OH-IMI, in doses of 5-6 mg/kg, compared to dosages of
      IMI up to 8.5 mg/kg, produced a significantly greater incidence of life
      threatening arrhythmias, and caused profound and significant decreases in blood
      pressure and cardiac output. 2-OH-IMI had a smaller volume of distribution (Vd)
      and shorter half-life. CNS penetration, as estimated by CSF/plasma ratios, was
      significantly greater for 2-OH-IMI. These phenomena were partly accounted for by
      significantly less protein binding for the hydroxymetabolite. It is concluded
      that 2-OH-IMI has increased penetrance into the CNS despite a smaller Vd and that
      it is significantly more cardiotoxic than its parent.

PMID- 1365673
TI  - Tolerance, withdrawal, and supersensitivity to dopamine mediated cues in a drug
      drug discrimination.
AB  - Rats were trained to discriminate between 0.25 mg/kg amphetamine (AMPH) and 0.03
      mg/kg haloperidol (HAL) in a two-lever drug discrimination task. In order to test
      for a drug-induced withdrawal state, animals were assigned to one of three
      chronic treatment groups and given injections of AMPH, HAL, or distilled water
      (DW) for 10 consecutive days. Subjects from each treatment condition were then
      tested at 24, 48, or 72 h after the final injection. At the 24 h retest interval,
      subjects injected with AMPH responded as though administered an acute dose of HAL
      (0.028 mg/kg) and subjects injected with chronic HAL responded as though
      administered an acute dose of AMPH (0.15 mg/kg). By 72 h choice behavior had
      returned to pretreatment values. To determine whether the rebound observed after
      10 days of drug treatment was present after a single injection, independent
      groups of subjects were injected with single doses of either 10 mg/kg AMPH or 1.0
      mg/kg HAL and then retested from 4 h to 48 h later. Single doses of both AMPH and
      HAL produced significant rebounds that peaked between 20 h (AMPH) and 24 h (HAL)
      following administration. In a third experiment, animals were tested with or
      without acute doses of drug following pretreatment with either HAL or AMPH.
      Receptor supersensitivity accounts for the tolerance observed to HAL 24 h after
      treatment with 1.0 mg/kg HAL, whereas receptor subsensitivity accounts for the
      tolerance observed 20 h after treatment with 10 mg/kg AMPH.

PMID- 1365674
TI  - Specific effects of the benzodiazepine midazolam on visual receptive fields in
      light and dark adapted human subjects.
AB  - Psychophysical experiments in humans have revealed similar characteristics of
      visual receptive fields as were found in cats and monkeys from retinal ganglion
      cell recordings. In addition, in some retinal ganglion cells of cats the GABA
      antagonist bicuculline decreases the activity of the inhibitory surround. These
      findings led to two predicitions: 1) benzodiazepines will selectively increase
      the inhibitory surround of human visual receptive fields, 2) after dark
      adaptation, no free GABA will be available in the synapses and benzodiazepines
      will have no effect on the visual system. Characteristics of human receptive
      fields were determined by subthreshold summation: the contrast threshold of a
      vertical line was measured dependent on the distance of two parallel flanking
      lines whose contrast was below threshold. Both hypotheses were confirmed: the
      threshold in the inhibitory region of receptive fields was specifically increased
      in a dose-dependent manner by midazolam PO (7.5 mg: P < 0.05; 15 mg: P < 0.01).
      In dark-adapted subjects no effect of midazolam was found. Control experiments
      with atropine (1 mg IV), sulpiride (100 mg IM), and levodopa (100 mg PO) showed
      no specific effect. The visual system may be a model to bridge the gap between
      animal and human psychopharmacology.

PMID- 1365675
TI  - Activation of 5-HT1C-receptors suppresses excessive wheel running induced by semi
      starvation in the rat.
AB  - Male Wistar rats were housed in cages linked to running wheels and fed on a
      schedule designed to reduce their body weight by 20-30%. During this period of
      semi-starvation the rats increased their daily running wheel activity (RWA) by up
      to 30 km/day. RWA could be kept at this level provided that body weight was kept
      constant. Different serotonin receptor (5-HT) agonists and antagonists were
      tested for their effects on RWA and it was found that RWA could be suppressed
      only by agonists with high affinity for the 5-HT1C receptor (TFMPP, mCPP, DOI and
      quipazine). Serotonin receptor agonists, which do not pass the blood-brain
      barrier, and 5-HT itself had no effect on RWA. The inhibitory effect of the
      agonists on RWA was prevented by pretreatment with antagonists that also had high
      affinity for 5-HT1C receptors (mianserin, metergoline and mesulergine). From
      these results we conclude that semi-starvation-induced hyperactivity can be
      blocked by 5-HT1C agonists. Furthermore we suggest that the animal model
      presented in this study might be a useful tool for in vivo studies on selective 5
      HT1C receptor activation.

PMID- 1365676
TI  - Forced-choice versus free-choice procedures: caffeine self-administration in
      humans.
AB  - Methodological comparisons of procedures for drug self-administration are rare.
      In studies examining the reinforcing effect of caffeine in humans, caffeine self
      administration usually has been inferred from performance under forced-choice
      procedures. In the present experiment, caffeine self-administration via coffee
      was compared under forced-choice and free-choice conditions; i.e., when subjects
      were and were not required to use a minimum number of coffees. Ten moderate
      coffee drinkers (2-7 cups/day) were assigned to forced- and free-choice
      conditions using a randomized cross-over design. Under each choice condition,
      subjects completed six independent, double-blind trials, consisting of a 2-day
      exposure period followed by a 2-day test period. During exposure, subjects
      consumed either decaffeinated or caffeinated (100 mg/serving) coffee on day 1 and
      the other coffee on day 2. During the test period, subjects had concurrent access
      to the same decaffeinated and caffeinated coffees. Under the forced-choice
      condition, subjects were required to drink at least four cups of coffee per day
      during the test period. Under the free-choice condition, subjects did not have a
      minimum-cup requirement. In general, the relative rate at which subjects self
      administered caffeinated versus decaffeinated coffee was similar across choice
      conditions, even though subjects self-administered significantly fewer cups of
      both coffee types under the free-choice than the forced-choice condition. These
      results suggest that, at least for caffeine, forced-choice and free-choice
      procedures produce comparable results. Whether this finding generalizes to a
      context in which caffeine or another drug is more robustly self-administered,
      remains to be determined.

PMID- 1365677
TI  - Oral ethanol self-administration in rats is reduced by the administration of
      dopamine and glutamate receptor antagonists into the nucleus accumbens.
AB  - The purpose of this study was to assess the role of endogenous dopamine and
      glutamate systems within the nucleus accumbens in modulating responses for oral
      ethanol reinforcements (10% w/v) in a free-choice operant task. Pretreatment with
      both systemic (100 micrograms/kg) and intra-nucleus accumbens microinjection of
      fluphenazine (2 and 4 micrograms), a dopamine receptor antagonist, significantly
      decreased responding for ethanol, without significantly affecting responses for
      water. Ethanol self-administration was also attenuated by microinjection into the
      nucleus accumbens of 2-amino-5-phosphopentanoic acid (AP-5, 3 and 6 micrograms),
      a competitive NMDA receptor antagonist. These results suggest that dopamine and
      glutamate neurotransmission in the nucleus accumbens may regulate ethanol self
      administration and its reinforcing effects.

PMID- 1365678
TI  - Drug discrimination studies in rats with caffeine and phenylpropanolamine
      administered separately and as mixtures.
AB  - The discriminative stimulus effects of mixtures of caffeine and
      phenylpropanolamine (PPA) have been investigated because these drugs have been
      abused together. Rats were trained to discriminate caffeine (20 mg/kg), PPA (20
      mg/kg), or a mixture of both drugs, from saline in a two-bar operant conditioning
      procedure with food reinforcers presented on a tandem VI-FR schedule.
      Discriminations of mixture, caffeine alone and PPA alone were 90% accurate after
      40 sessions. Generalisation to both PPA and caffeine was weak (25-47%) at the
      doses used in the training mixture, although there was almost complete
      generalisation to larger doses of PPA. Under these conditions, there was a
      possible synergistic interaction between caffeine and PPA because the
      discriminative effect of the mixture could not be fully explained by the combined
      effects of its component drugs. However, in rats trained on caffeine, PPA had no
      effect on the dose-response relationship for caffeine; similarly, in rats trained
      on PPA, caffeine had no effect on the dose-response relationship for PPA (no
      synergism or antagonism). Generalisation to (+)-amphetamine and cocaine was
      weakest in rats trained on caffeine, was partial in rats trained on the mixture,
      and was complete in rats trained on PPA; thus, the mixture of caffeine and PPA
      was not more like cocaine or amphetamine than PPA alone. The results are in
      agreement with reports that caffeine and PPA may interact in a complex manner,
      but do not support the view that the interaction enhances their resemblance to
      highly abused stimulants such as amphetamine and cocaine.

PMID- 1365679
TI  - The science of biological specimen preparation for microscopy and microanalysis
      1990. Proceedings of the 9th Pfefferkorn Conference. Santa Cruz, California,
      August 6-10, 1990.

PMID- 1365680
TI  - Radiation-associated sarcoma of bone and soft tissue.
AB  - Radiation-associated sarcomas are uncommon, constituting less than 5% of all
      sarcomas, and generally associated with a poor prognosis. We reviewed the medical
      records of 565 patients with sarcoma and a second malignancy seen at our
      institution between 1943 and 1989; 160 of these patients (28%) were considered to
      have a radiation-associated sarcoma. The most common diagnosis for which
      radiation had been given was breast cancer (26%), followed by lymphoma (25%) and
      carcinoma of the cervix (14%). The most common histologic types of radiation
      associated sarcoma were osteogenic (21%), malignant fibrous histiocytoma (16%),
      and angiosarcoma/lymphangiosarcoma (15%). Most of the tumors were high grade
      (87%). Three variables had prognostic significance in multivariate analysis: the
      presence of metastatic disease, the completeness of operative resection in
      patients with localized disease, and the size of the primary tumor in patients
      who underwent complete resection of the sarcoma. Survival was independent of
      histologic subtype or site of disease.

PMID- 1365681
TI  - Prognostic factors in node-negative breast cancer.
AB  - One hundred patients with node-negative breast cancer were examined to analyze
      the influence of tumor size, nuclear grade, and DNA content determined by flow
      cytometry on overall survival. Patients with diploid cancers lived significantly
      longer than those with aneuploid cancers (126 +/- 8 vs 80 +/- 11 months).
      Patients with an S-phase fraction less than 10% lived significantly longer than
      those with S-phase fractions 10% or greater (122 +/- 8 vs 85 +/- 10 months).
      Tumor size had the major impact on survival, and multivariate analysis of
      variance by the Cox proportional hazards model showed the greatest effect on
      prognosis. Tumor grade did not significantly influence overall survival.

PMID- 1365682
TI  - Ten-year follow-up of breast carcinoma in situ in Connecticut.
AB  - Statistics from the Connecticut Tumor Registry from 1979 to 1988 were examined,
      and individual medical records from 1979 to 1983 were also reviewed. Three
      hundred nineteen medical records were available for review, documenting 220 cases
      of ductal carcinoma in situ and 102 cases of lobular carcinoma in situ. In 1979,
      there were 33 new cases of ductal carcinoma in situ reported to the Connecticut
      Tumor Registry, representing 1.8% of all breast cancers. There has been a yearly
      increase in ductal carcinoma in situ, with 200 new cases, or 7.4% of all breast
      cancers, reported in 1988. Forty-eight (22%) of 217 patients with ductal
      carcinoma in situ had bilateral breast involvement with ductal carcinoma in situ
      or an invasive breast cancer. Ten (83%) of 12 mastectomy specimens from patients
      with ductal carcinoma in situ who presented with nipple discharge demonstrated
      residual tumor, suggesting a more diffuse involvement. Two of the three reported
      recurrences involved nipple discharge. Thirty-seven (16.8%) of the 220 patients
      with ductal carcinoma in situ and six (5.9%) of the 102 patients with lobular
      carcinoma in situ were diagnosed as having another unrelated cancer. Ongoing
      clinical trials will direct optimum therapy for patients increasingly diagnosed
      as having ductal carcinoma in situ.

PMID- 1365683
TI  - Potency, cure, and local control in the operative treatment of rectal cancer.
AB  - Impotence due to parasympathetic nerve injury is one of the most feared
      consequences of operations for treatment of rectal cancer. Sharp dissection along
      the parietal pelvic fascia where the parasympathetic nerves are located
      significantly reduces the incidence of pelvic failure. Autonomic nerve-preserving
      pelvic sidewall dissections, which combined the benefits of en bloc parietal
      pelvic dissection with nerve preservation, were performed in 42 men who were
      undergoing sphincter-preserving operations for treatment of rectal cancer. Thirty
      three (86.7%) of the 38 evaluable patients have remained potent, and 29 (87.9%)
      of the 33 patients have normal ejaculation. Deliberate sacrifice of the inferior
      hypogastric plexus caused only minor sexual dysfunction. Cancer recurred locally
      in only one patient (with stage D cancer). Autonomic nerve-preserving pelvic
      sidewall dissection combines the benefits of curative resection and local control
      with reduced morbidity, and it preserves potency.

PMID- 1365684
TI  - Lung resection for colorectal metastases. 10-year results.
AB  - BACKGROUND: Metastasectomy for colorectal carcinoma to the lung is controversial.
      We analyzed results of this approach to justify its credibility. METHODS: We
      studied 144 patients by retrospective review after complete resection of lung
      metastases from colorectal cancer from 1965 through 1988. Patient selection and
      prognostic factors influencing survival were analyzed. Survival was analyzed by
      the Kaplan-Meier method, and comparisons were made by log-rank analysis. RESULTS:
      A total of 170 thoracotomies were performed in 144 patients. The overall 5- and
      10-year survival was 40% and 30%, respectively. Those patients undergoing
      complete resection of their metastases survived significantly longer than those
      undergoing incomplete resections. CONCLUSION: It appears that resection of
      pulmonary metastases from colorectal carcinoma translates into long-term survival
      benefit.

PMID- 1365685
TI  - Resection of lung metastases from soft-tissue sarcomas. A multivariate analysis.
AB  - From 1970 through 1986, 78 patients underwent 162 thoracotomies for removal of
      lung metastases from soft-tissue sarcomas. A multivariate analysis showed that
      the presence of a local recurrence, an incomplete pulmonary resection, and a
      shorter disease-free interval were poor prognostic factors. Patients who
      underwent multiple thoracotomies survived longer from the time of initial
      thoracotomy. The histologic type of sarcoma and the number of metastases resected
      showed no statistical significance. The median survival of the 61 patients who
      had a complete resection was 21 months. Patients with five or fewer metastases
      resected had an overall 5-year survival of 22% compared with 21% for patients who
      had six or more metastases resected. However, patients with five or fewer
      metastases showed a trend toward a higher 10-year disease-free survival. A
      complete resection of pulmonary metastases from soft-tissue sarcoma can prolong
      survival even if multiple metastases are present, although patients with fewer
      metastases may have a longer disease-free survival.

PMID- 1365686
TI  - Recurrence patterns and outcome in 1019 patients undergoing axillary or inguinal
      lymphadenectomy for melanoma.
AB  - Patterns of recurrence and outcome were determined in 403 patients with melanoma
      who underwent an axillary or inguinal lymphadenectomy. Recurrences developed at
      single sites in 291 (72%) patients, with a median survival of 11 months, and at
      multiple sites in 112 (28%) patients, with a median survival of 3 months. Among
      patients with single-site recurrence, those with nonvisceral recurrence (n = 190)
      had a median survival of 18.5 months compared with 6 months in those with
      visceral recurrence (n = 101). Recurrences were treated surgically in 240 (60%)
      patients, with a median survival of 15 months, and nonsurgically in 112 patients,
      with a median survival of 4 months. Median survival after complete resection of
      single-site recurrence was 19 months compared with 6 months after incomplete
      resection. Multivariate analysis revealed that outcome was improved by surgical
      treatment, single-site and nonvisceral recurrence, and primary site in an
      extremity. These observations support an approach of selective resection in the
      treatment of recurrences after lymphadenectomy.

PMID- 1365687
TI  - Immunotherapy with a tumor-infiltrating lymphocyte clone, soluble antigen, and
      cyclophosphamide.
AB  - A tumor-specific cytotoxic T-lymphocyte clone derived from bulk cultures of tumor
      infiltrating lymphocytes attenuated the outgrowth of methylcholanthrene (MCA)
      induced fibrosarcomas in C3H/HeJ mice. In 4-hour chromium 51-release assays, bulk
      cultures of tumor-infiltrating lymphocytes showed nonspecificity for MCA-induced
      tumors (MCA-F, MCA-D, MCA-SP), YAC-1, and EL-4. In contrast, a cytotoxic T
      lymphocyte-cloned line specifically killed MCA-F, but not MCA-D or MCA-SP.
      Cytotoxic T-lymphocyte line 8 protected syngeneic hosts in local and systemic
      adoptive transfer assays. Hosts bearing 4-day-established MCA-F tumor cells
      received single agents or combinations of isoelectrophoretically purified butyl
      alcohol-extracted tumor-specific transplantation antigen (1 microgram/wk),
      cyclophosphamide (20 mg/kg on days 4 and 11), and/or cytotoxic T-lymphocytes (1 x
      10(7) cells on days 7 and 14). While the mean tumor diameter was 11.6 +/- 1.3 mm
      in untreated hosts or after single treatments, the combination of tumor-specific
      transplantation antigen and cyclophosphamide along with the cytotoxic T
      lymphocyte clone resulted in tumor diameters of 1.8 +/- 0.5 mm. The triple
      combination prolonged host survival from 39.6 +/- 1.6 to 57.2 +/- 4.7 days
      compared with antigen and cyclophosphamide treatment.

PMID- 1365688
TI  - A small-bowel segment as a total extrahepatic bile duct replacement.
AB  - The effect of a small-bowel segment as a total extrahepatic bile duct
      replacement, with preservation of the bile passage through the papilla of Vater,
      was examined in 12 pigs followed up for 420 days. No complications during or
      after surgery were observed in any of the animals. The laboratory parameters were
      within normal range during the entire observation period. No anastomotic stenosis
      was evident on percutaneous transhepatic cholangiography in animals examined 2,
      6, or 12 months after surgery. The intrahepatic biliary tract was not dilated.
      There was obvious peristalsis of the grafted small-bowel toward the papilla of
      Vater. Autopsies showed that the grafts had healed without any sign of
      irritation. Histologically, the structure of the graft remained undisturbed.
      There was a clear distinction between the mucosa of the bile duct and that of the
      small bowel, with no sign of chronic infection. In the graft as well as in the
      vascular pedicle, the nerve fibers were intact. Liver biopsy showed no pathologic
      changes. In light of the results of these experiments, the small-bowel segment
      appears to be a very promising substitute for the injured extrahepatic biliary
      duct.

PMID- 1365689
TI  - Nuclear DNA analysis of hyperplastic parathyroid glands in multiple endocrine
      neoplasia type I.
AB  - Twenty-four hyperplastic parathyroid glands from 11 patients with multiple
      endocrine neoplasia type I (MEN-I), and 36 hyperplastic parathyroid glands in 15
      patients with sporadic primary hyperparathyroidism, ie, not associated with MEN,
      were analyzed for DNA by flow cytometry. Sixteen of 24 hyperplastic parathyroid
      glands from patients with MEN-I were DNA diploid, and eight were DNA aneuploid.
      Thirty-three of 36 hyperplastic parathyroid glands from patients without MEN were
      DNA diploid, and only three were DNA aneuploid. The mean percentage of 4c level
      (a measure of the G2M phase of the cell cycle) of DNA diploid hyperplastic
      parathyroid glands taken from patients with MEN-I was 8.1% +/- 4.5%, which is
      significantly higher than the 3.5% +/- 3.4% for those taken from patients without
      MEN. Our results show that there is a difference in nuclear DNA content between
      hyperplastic parathyroid glands in patients with MEN-I and those in patients
      without MEN.

PMID- 1365690
TI  - Photodynamic therapy in the management of neoplasms of the perianal skin.
AB  - Perianal extramammary Paget's disease, Bowen's disease, and squamous cell
      carcinoma are three entities that are very rarely reported. Overall, it is
      generally accepted that wide surgical excision is adequate treatment except under
      certain circumstances. Consideration has to be given to invasiveness, metastatic
      potential, multicentricity, and tendency to recur. We describe four patients who,
      following unsuccessful multiple attempts at achieving microscopically clear
      margins with surgical excision, were treated at Roswell Park Cancer Institute
      with photodynamic therapy with a surface illumination method. With a minimum
      follow-up of 6 months (more than 1 year in three patients), there have been no
      recurrences to date.

PMID- 1365691
TI  - Paragangliomas of the neck.
AB  - Between 1967 and 1990 inclusive, 28 patients with paragangliomas of the neck were
      diagnosed at the University of Alabama at Birmingham Affiliated Hospitals. There
      were 11 men and 17 women, whose ages ranged from 12 to 76 years (mean, 47 years).
      Tumor locations included the carotid bodies (19 cases), the vagus nerves (three),
      supraglottic larynx (two), the left lateral pharyngeal wall (one), posterior to
      the right jugular vein (not otherwise defined) (one), subcutaneous neck tissue
      (one), and a cervical lymph node with unknown primary (one). Diagnostic workup
      included angiography (23 cases) with preoperative embolization (three), computed
      tomography (one), magnetic resonance imaging (two), and urinary catecholamine
      assay (four). All 28 patients underwent resection of the lesions. Cranial nerve
      damage occurred in 11 patients (39%). There were no perioperative deaths or
      cerebrovascular accidents, although one of two saphenous vein grafts became
      thrombotic after carotid body tumor resection.

PMID- 1365692
TI  - Randomized trial of preoperative chemotherapy for squamous cell cancer of the
      esophagus. The Chirurgische Arbeitsgemeinschaft Fuer Onkologie der Deutschen
      Gesellschaft Fuer Chirurgie Study Group.
AB  - Of 77 patients with potentially resectable squamous cell carcinoma of the
      esophagus who were asked to participate in a phase III trial of treatment with
      either immediate surgery (n = 24) or surgery plus preoperative chemotherapy (n =
      22), only 46 agreed to randomization. A priori, 13 patients chose chemotherapy
      before surgery and 18 patients chose surgery only. The complete chemotherapy
      program consisted of three cycles with fluorouracil, 1 g/m2 per day for 5 days,
      and cisplatin, 20 mg/m2 per day for 5 days. The response rate to chemotherapy was
      50% (17 of 34 patients). Side effects of therapy were higher than expected based
      on results of previous phase II studies. Two drug-related deaths were observed.
      The resectability rate for patients in the surgery only group was 79% (33 of 42
      patients) compared with 70% (19 of 27 patients) for patients receiving
      chemotherapy. The postoperative rates of septic complications (41% [11 of 27
      patients] vs 26% [11 of 42 patients]) and respiratory disorders (48% [13 of 27
      patients] vs 31% [13 of 42 patients]) were higher for patients with preoperative
      chemotherapy than for those treated with surgery only. Surgery-related mortality
      was increased in the chemotherapy group (19% [five of 27 patients]) compared with
      the surgery only group (10% [four of 42 patients]). Patients responding to
      preoperative chemotherapy had prolonged survival (median, 13 months) compared
      with nonresponders (median, 5 months), but the median survival for the
      chemotherapy group and the surgery only group was identical (10 months). We
      conclude that the preoperative chemotherapy regime used in this multi
      institutional trial neither influences resectability nor increases the overall
      survival of patients with localized esophageal cancer. However, preoperative
      chemotherapy is associated with considerable side effects and a high
      postoperative mortality rate.

PMID- 1365693
TI  - The horror autotoxicus and multiple-organ failure.
AB  - An injury or operation with tissue injury, ischemia, and sepsis provokes a
      neuroendocrine, immune, and inflammatory response to promote survival and heal
      the wound. If the injury is massive or complicated by infection, the inflammatory
      response may become generalized and excessive, producing organ and tissue damage
      and multiple-organ failure, a modern "horror autotoxicus." Many inflammatory
      mediators have been identified. In isolated organs, the use of blocking mediators
      to prevent combined ischemia-reperfusion injury is feasible. With regional
      ischemia, activator attenuation may be possible. It is unclear whether blockade
      or modulation of all or part of an excessive inflammatory response will be
      possible, helpful, and without hazard in patients with multisystem injuries or
      sepsis. Feedback loops and control mechanisms of these systems will better define
      such possibilities. Employment of growth factors and other protective agents to
      stimulate wound healing, infection control, and host resistance may be more
      helpful. Ultimately, prevention of multiple-organ failure requires sound surgical
      judgment, techniques, and organ support.

PMID- 1365694
TI  - The hypothalamic-pituitary-adrenal-immune axis. A critical assessment.
AB  - The hypothalamic-pituitary-adrenal (HPA) system has been a model for
      neuroendocrine control of responses of organisms to stressors since the turn of
      the century. Despite this, the pathways by which infectious insults interact with
      the HPA system remained poorly defined. Recently, evidence has been presented
      suggesting that humoral mediators released by inflammatory cells (cytokines) may
      participate in two-way communication between the site of inflammation and the
      central nervous system. In this review, we detail the current understanding of
      the responses of the HPA system to the classic physiologic stimuli of hypovolemia
      and pain, with an emphasis on the cellular mechanisms and mediators discovered in
      recent years. We also examine the data substantiating a role of interleukin 1,
      interleukin 6, and tumor necrosis factor in the direct humoral activation of the
      HPA system and consider the evidence favoring a physiologic negative feedback
      relationship between the HPA and the immune systems. Such as interaction is an
      exciting concept with broad clinical implications. However, we believe that the
      temporal and quantitative aspects of experiments designed to evaluate this
      interaction must be carefully evaluated to assure that true physiologic stimuli
      are studied and that the responses observed are not due to pharmacologic effects
      of inflammatory mediators acting through "classic" neuroendocrine pathways.

PMID- 1365695
TI  - Nodular hyperplasia, black thyroid, and chronic minocycline ingestion in a
      teenager.
AB  - An 18-year-old man with left-lobe thyroid hemiagenesis underwent isthmectomy for
      management of a nodule that failed to take up radioactive iodine during a nuclear
      scan. The resected tissue, which demonstrated nodular hyperplasia, and the
      remaining right lobe, were black. The association between deep staining and
      chronic minocycline ingestion was subsequently recognized. Twelve years later,
      the patient remained asymptomatic, suggesting that complete resection of
      tetracycline-stained thyroid tissue is unnecessary.

PMID- 1365696
TI  - Biliary cystadenocarcinoma arising from benign cystadenoma.

PMID- 1365697
TI  - Relationship of first-trimester subchorionic bleeding detected by color Doppler
      ultrasound to subchorionic fluid, clinical bleeding, and pregnancy outcome.
AB  - We analyzed retrospectively the incidence of subchorionic fluid and embryonic
      death in 2116 consecutive patients evaluated with abdominal ultrasound and 783
      patients evaluated with vaginal ultrasound. These women were examined during the
      first 12 postmenstrual weeks and had conceived as a result of infertility
      treatment. In addition, we analyzed the relationship of subchorionic bleeding to
      subchorionic fluid in 230 patients evaluated with color Doppler ultrasound and
      the relationship of subchorionic bleeding to clinical bleeding, precipitating
      factors, pregnancy outcome, and the karyotypes of abortuses. In single
      gestational sac pregnancies, subchorionic fluid was found equally often in women
      scanned with vaginal or color Doppler ultrasound, and less often with abdominal
      ultrasound (P less than .0001). Embryonic death was increased only in patients
      with large amounts of subchorionic fluid observed on abdominal ultrasound. Color
      Doppler ultrasound revealed subchorionic bleeding in 87 of 235 ultrasound scans
      (37%) and in 48 of 102 patients (47%) when subchorionic fluid was present.
      Subchorionic bleeding was associated with moderate or large amounts of
      subchorionic fluid (P = .041), with precipitating events (P less than .0001), and
      with clinical bleeding (P = .001). It was occult in ten of 48 patients (21%).
      Embryonic death occurred equally often in women with no fluid and in those with
      subchorionic fluid, with and without subchorionic bleeding. Abortuses were
      karyotypically abnormal in an equal proportion of cases with subchorionic
      bleeding, subchorionic fluid, and no fluid. These findings indicate that
      subchorionic fluid and subchorionic bleeding are common findings in early
      pregnancy and are not associated with embryonic death unless they are accompanied
      by clinical bleeding.

PMID- 1365698
TI  - Ritodrine therapy in the presence of chronic abruptio placentae.
AB  - BACKGROUND: Betamimetic therapy is usually contraindicated for the treatment of
      premature labor associated with abruptio placentae. We report prolongation of a
      pregnancy for 7 weeks using ritodrine despite the presence of placental
      abruption. CASE: A 33-year-old primigravid woman presented at 25 weeks' gestation
      with irregular uterine contractions, vaginal bleeding, and sonographic evidence
      of abruptio placentae. Port wine-colored amniotic fluid was found during
      amniocentesis, and serial hematocrits decreased from 36 to 25%. A diagnosis of
      abruptio placentae was made, and because the maternal cardiovascular and fetal
      biophysical indices were normal, tocolytic therapy was started. Before the
      administration of ritodrine, the patient and her husband were given an extensive
      review of the risks, including blood transfusion, adult respiratory distress
      syndrome, disseminated intravascular coagulopathy, and maternal or fetal death.
      CONCLUSION: Although clinical suspicion of abruptio placentae remains a
      contraindication to betamimetic therapy, exceptions may be made if fetal and
      maternal well-being can be monitored and if a fully staffed operating room is
      always available for immediate cesarean delivery. The benefits of this management
      may outweigh the associated risks for carefully chosen, very preterm gestations.

PMID- 1365699
TI  - Colouterine fistula complicating diverticulitis: charcoal challenge test aids in
      diagnosis.
AB  - Fistula formation between a segment of colon and the uterus is an unusual
      complication of diverticulitis; only 17 cases have been reported in the world
      literature. We describe a 69-year-old woman with a colouterine fistula secondary
      to diverticulitis. She presented with a malodorous vaginal discharge that grew
      multiple enteric organisms on culture. A barium enema revealed colonic
      diverticula but no fistula tract. Orally administered activated charcoal was seen
      flowing from the cervical os during a pelvic examination the following day,
      establishing a diagnosis of colouterine fistula. Pathologic examination of the
      resected colon and uterus confirmed this diagnosis and determined that
      diverticulitis was the etiology. From a review of the literature, we conclude
      that radiographic and invasive procedures cannot be depended upon for diagnosis.
      Ingestion of activated charcoal may provide a simple, noninvasive approach to the
      diagnosis of enterouterine fistulas.

PMID- 1365700
TI  - Therapy of peroxisomal disorders.

PMID- 1365701
TI  - Retinotopic organization of striate and extrastriate visual cortex in the golden
      hamster (Mesocricetus auratus).
AB  - The visual topography within striate and lateral extrastriate visual cortices was
      studied in adult hamsters. The cortical areas 17 and 18a in the left hemisphere
      were electrophysiologically mapped upon stimulation of the right eye, correlating
      receptive field positions in the visual field with cortical recording sites.
      Reference lesions were placed at selected cortical sites. Like in rats and other
      mammals, the lateral extrastriate cortex contained multiple representations of
      the visual field. Rostral area 18a contained the rostrolateral maps, with medial
      and lateral divisions. More caudally and sharing a common border with V1, maps in
      lateromedial, posterolateral and posterior areas were found. More laterally and
      forming a "third tier" of visual maps, anterolateral, laterolateral-anterior,
      laterolateral and laterolateral-posterior areas were found. There was also an
      indication of a possible pararhinal map. The plan so defined is virtually
      identical to that of rats. The results may be useful to understand a basic
      mammalian plan in the organization of the visual cortex.

PMID- 1365702
TI  - Brain connections: interhemispheric fiber systems and anatomical brain
      asymmetries in humans.
AB  - The present review summarizes some results of a research program oriented to
      determine the anatomical substrates of interhemispheric communication in humans,
      as seen in postmortem material. One main finding is a sensible pattern of
      histological differentiation along the corpus callosum, indicating specific
      properties of interhemispheric conduction for axonal fibers involved in different
      brain functions. Callosal regions that connect primary and secondary sensory and
      motor areas are characterized by a large proportion of fast-conducting, large
      diameter fibers, while regions connecting the so-called association areas and
      prefrontal areas bear a high density of slow-conducting, lightly myelinated and
      thin fibers. These findings are interpreted in a functional context, suggesting
      that the fast-conducting fibers connecting sensory and motor areas contribute to
      fuse the two hemirepresentations in each hemisphere. It has also been determined
      that an increased callosal area indicates an increased number of callosal fibers,
      a finding that validates previous morphometric studies done in several
      laboratories. No sex differences in callosal size, shape, or in callosal fiber
      composition were found. Finally, an inverse relation was found between the
      anatomical asymmetries in the size of the Sylvian fissure and the size and number
      of fibers in specific segments of the corpus callosum. There were sex differences
      in terms of the particular callosal regions showing a significant correlation
      with asymmetries, and in terms of the fiber types that were correlated with
      asymmetries.

PMID- 1365703
TI  - Molecular biology of the amyloid of Alzheimer's disease. An overview.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder that affects a
      significant percentage of elderly individuals. Degenerative nerve cells express
      atypical proteins, and amyloid is deposited. The hallmark event of Alzheimer's
      disease is the deposition of amyloid as insoluble fibrous masses in extracellular
      neuritic plaques and around the walls of cerebral blood vessels. This review will
      focus on the advances on the knowledge of Alzheimer's amyloid, because it is
      becoming increasingly clear that the deposition of amyloid on neuritic plaques in
      the brain represents the earliest and most characteristic pathological feature of
      Alzheimer's disease. The main component of amyloid is a 4.2-4.5 KDa hydrophobic
      peptide, named amyloid beta-peptide, that is codified in chromosome 21 as part of
      a much larger precursor protein. The study of the mechanism by which the amyloid
      beta-peptide arises from the amyloid precursor protein is very important in order
      to understand the biological basis of amyloid deposition and its role in
      Alzheimer's disease.

PMID- 1365704
TI  - The separation and identification of picomole amounts of intermediates of glucose
      metabolism by high performance liquid chromatography on pellicular resins.
AB  - A column (CarboPac PA1, Dionex) containing an anion-exchange pellicular resin was
      used for the separation of phosphoryl-hexoses derived from labeled glucose
      microinjected into individual frog oocytes or from cultures of Escherichia coli.
      Intermediates were identified by: a) comparison of retention times with those of
      authentic commercial compounds; b) the use of internal labeled standards; c)
      incubation of samples with specific enzymes and noting the disappearance of one
      radioactive peak and appearance of another at a new retention time.

PMID- 1365705
TI  - Prostaglandin-E2 and cyclic adenosine 3'-5' monophosphate levels in the
      hypertrophied rat heart.
AB  - To assess whether prostaglandin-E2 (PGE2) and cyclic adenosine 3'-5'
      monophosphate (cAMP) are involved in the cardiac response to chronic pressure
      overload, we measured by specific radioimmunoassay method the cardiac tissue and
      plasma concentrations of PGE2 and cAMP in an animal model of left ventricular
      hypertrophy. The cardiac hypertrophy was accompanied by a significant increase in
      PGE2 content, and a significant decrease in cAMP content, in the heart. In
      addition, we found elevated PGE2 and cAMP levels in arterial plasma samples from
      the rats with hypertrophied hearts compared to normal rats. These findings
      suggest a link between cardiac and vascular PGE2 and cAMP generation and the
      hemodynamic stresses of advanced cardiac overload.

PMID- 1365706
TI  - Golden hamster perivitelline spermatozoa do not show proacrosin/acrosin at the
      inner acrosomal membrane.
AB  - It has been suggested that acrosin may function in penetration of the zona
      pellucida and of the highly structured extracellular matrix of the perivitelline
      space. In this study we investigated whether golden hamster perivitelline
      spermatozoa contain proacrosin/acrosin, as evidenced by the silver enhanced
      immunogold technique using the monoclonal antibody antiacrosin C2E5. None of the
      197 spermatozoa recovered from the perivitelline space showed proacrosin/acrosin
      associated with the acrosomal region, suggesting that acrosin would not play a
      role in the penetration of the perivitelline extracellular matrix.

PMID- 1365707
TI  - Synergistic effect of cortisol and thyrotrophin releasing hormone on lung
      maturation in the fetal sheep entails connective tissue maturation.
AB  - Pressure-volume relationships and collagen and elastin contents were measured in
      the lungs of fetal sheep infused either with saline (n = 4), thyrotrophin
      releasing hormone (TRH; n = 6), cortisol (n = 9) or TRH plus cortisol (n = 10) at
      128 days of gestation (term = 149 days) for 7 days. Lung distensibility (V40 =
      1.8 +/- 0.1 ml/g wet wt; mean +/- SD) and stability (V5 = 0.6 +/- 0.1) increased
      along with collagen (C) (10.1 +/- 2.7 micrograms/mg) and elastin (E) contents
      (128 +/- 35 ng/mg) in the animals infused with TRH plus cortisol and were
      significantly higher (p < 0.05) than those observed in TRH (V40 0.62 +/- 0.07; V5
      0.32 +/- 0.04; C 3.53 +/- 1.3; E 38.2 +/- 8.3), cortisol (V4 0.66 +/- 0.6; V5
      0.27 +/- 0.03; C 4.27 +/- 0.8; E 41.02 +/- 12.7) or saline infused fetuses (V40
      0.40 +/- 0.1; V5 0.20 +/- 0.06; C 3.28 +/- 0.9; E 31.5 +/- 9.2). Plasma
      concentrations of prolactin (PRL), triiodothyronine (T3) and cortisol (F) were
      also higher in the group of fetuses infused with both hormones in comparison with
      the other groups. In fetuses treated with TRH plus cortisol, PRL (32 +/- 8.3
      ng/ml) and T3 (308.3 +/- 36 micrograms/dl) were significantly higher than in
      those infused with cortisol alone (PRL 3.7 +/- 2.3; T3 128 +/- 30) or with saline
      (PRL 4.2 +/- 1.6; T3 < 5 micrograms/dl). In the group treated with TRH alone, PRL
      also increased significantly (37 +/- 6.4), but T3 increased only slightly (18 +/-
      3.4).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1365708
TI  - The determination of the average 27Al-31P distance in aluminophosphate molecular
      sieves with SEDOR NMR.
AB  - The average 27Al-31P distances in an aluminophosphate, AlPO4-5, and in a
      silicoaluminophosphate, SAPO-11, were determined by using Spin Echo DOuble
      Resonance (SEDOR). A calculated SEDOR curve was fitted to the data in order to
      obtain the dipolar coupling constant. The tetrahedral surrounding of 27Al by four
      31P atoms in the second coordination sphere was taken into account in the
      calculation of the theoretical SEDOR curve. The average 27Al-31P distances
      obtained by using this technique proved to be in good agreement with X-ray
      diffraction data.

PMID- 1365709
TI  - Solid state multinuclear NMR study of sigma-acetylide complexes of platinum,
      trans-[ClPt(PnBu3)2-C=C-p-C6H4-C=C-Pt(PnBu3)2Cl] and trans-[-Pt(PnBu3)2-C=C-p
      C6H4-C=C-]n.
AB  - Solid state 13C, 31P and 195Pt NMR has been employed to study the electronic and
      geometric structure of the dimeric and polymeric sigma-acetylide complexes of
      platinum, trans-[ClPt(PnBu3)2-C identical to C-p-C6H4-C identical to C
      Pt(PnBu3)2Cl] and trans-[-Pt(PnBu3)2-C identical to C-p-C6H4-C identical to C-]n.
      The 195Pt shielding tensor has been measured and analysed to reveal details about
      the electronic properties of the Pt-ligand bonds.

PMID- 1365710
TI  - CP/MAS of quadrupolar S = 3/2 nuclei.
AB  - The spin dynamics of Hartmann-Hahn cross-polarization from I = 1/2 to quadrupolar
      S = 3/2 nuclei is investigated. A density-matrix model applicable to cases where
      the quadrupole frequency vQ is much larger than the rf amplitude v1S of the S
      spins, predicts the time development of the spin state of an isolated I, S spin
      pair in static situations and in three distinct cases of magic-angle-spinning
      speed vR. These cases are characterized as slow, intermediate, and fast,
      depending on the magnitude of the parameter alpha = v1S2/vQvR relative to the
      intermediate value of 0.4. The model predictions are supported by numerical
      simulations. The polarization transfer from I to S is efficient in the limits of
      slow and fast sample spinning. When alpha << 1, the Hartmann-Hahn condition is
      shifted over once or twice vR. When the spinning rate is intermediate, poor spin
      locking of the quadrupolar spins prevents the accumulation of a cross
      polarization signal and, in addition, depletes the spin-locked I magnetization.
      Experimental CP/MAS data obtained in NaOH show that the concepts developed for
      isolated spin pairs are also applicable to cross-polarization in a strongly
      coupled multi-spin system.

PMID- 1365711
TI  - Heteronuclear X-Y double quantum MAS NMR in crystalline inorganic solids.
      Applications for indirect detection and spectral editing of rare-spin resonances.
AB  - Heteronuclear double quantum MAS NMR experiments in the solid state, involving
      pairs of highly abundant 31P spins and the rare spins 113Cd, 77Se, and 29Si, are
      described for the three crystalline compounds CdSiP2, CdGeP2, and Ag7PSe6. These
      experiments offer the opportunity of indirectly detecting the rare-spin resonance
      via chemical shift evolution of heteronuclear double quantum coherence. For
      suitable cases, this method results in significantly enhanced detection
      sensitivities. Criteria for favorable indirect detection experiments are
      established. Besides offering high sensitivity, the pulse sequence also acts as a
      heteronuclear double quantum filter, hence providing heteronuclear correlation
      and useful spectral editing for peak assignments.

PMID- 1365713
TI  - Cross-polarisation to low-gamma nuclei: the first 183W CP/MAS spectra.
AB  - The possibility to obtain 183W CP/MAS spectra has been explored. The choice of
      suitable set-up compounds, convenient set-up procedures and experimental
      considerations with respect to contact times, TIS and T1 rho interplay, are
      discussed.

PMID- 1365712
TI  - Two-dimensional J-resolved and SUPERCOSY NMR experiments in the solid state.
AB  - Two 2D experiments, novel to solid-state NMR, are demonstrated using the
      trimethylsilyl ester of cubic octameric silicate (Q8M8). J-Resolved 13C NMR with
      BLEW-12 proton homonuclear decoupling reveals the scalar 13C-1H couplings and
      29Si SUPERCOSY the connectivities of silicon atoms in the distorted Q8 cube.

PMID- 1365714
TI  - Nuclear magnetic resonance of hydrogen sorbed by powdered palladium metal and
      alumina-supported palladium.
AB  - Hydrogen in 0.2 micron beta-palladium powder and in an alumina-supported
      palladium catalyst was investigated by NMR spectroscopy. The dependence of the
      shift on hydrogen pressure and the hydrogen-to-palladium (H/Pd) ratio in beta
      palladium hydride was determined for 273 K < T < 368 K. The activation energy for
      the process affecting the hydrogen shift is 9.4(+/- 0.5) kcal mol-1, similar to
      the enthalpy of transition from the alpha- to beta-phase. NMR measurements of
      hydrogen in alumina-supported palladium show a similar behavior, which may allow
      one to use NMR shifts as a barometer of the state of the hydrogen in the metal.

PMID- 1365715
TI  - Inhomogeneous interactions in solids under slow off-magic angle spinning.
AB  - The central band of an inhomogeneous interaction under slow off-magic angle
      spinning (off-MAS) is no longer a scaled static spectrum with scaling factor
      P2(cos upsilon), that is, the spectrum distortion occurs in comparison with that
      under the rapid rotation condition. The dependence of this distortion in the
      chemical shift spectrum, for instance, on anisotropy, the asymmetry parameter,
      spinning rate and the angle between the spinning axis and the applied magnetic
      field is studied in this paper. It is shown that the distortion can be partly
      eliminated by using TOSS in certain circumstances. Experimental evidence is
      presented in this study.

PMID- 1365716
TI  - Presentation of sideband envelopes by two-dimensional one-pulse (TOP)
      spectroscopy.
AB  - A novel way of representing 1D MAS spinning sideband spectra in a 2D-resolved
      fashion is explained. The method is illustrated with 2H MAS data of deuterated
      polycarbonate. From the resulting 2D spectrum, the isotropic shifts can be
      identified on one axis and the rotary echo decay spectra along the other axis.

PMID- 1365717
TI  - EPR and 1H and 13C dynamic nuclear polarization studies of a molecularly doped
      polymer: bisphenol A polycarbonate doped with trianisylamine and trianisylaminium
      perchlorate.
AB  - We have investigated the EPR and DNP behavior of a molecularly doped polymer
      modeling those used to transport electronic charge in electrophotography. The EPR
      spectra show no evidence of the superexchange reported for a closely related
      system based on tri-p-tolylamine. The difference may be due to larger charge
      transfer matrix elements in the latter system. An unambiguous interpretation of
      the observed 1H DNP was rendered difficult by the unanticipated asymmetry of the
      EPR spectra. We report extensive data on the "three-spin" effect evident in the
      DNP-enhanced 13C NMR spectra, and comment on its potential for characterizing
      polymer interfaces.

PMID- 1365718
TI  - On the 13C CP/MAS spectra of leucine.
AB  - The CP/MAS 13C NMR spectra of crystalline L-leucine and DL-leucine at 7 T are
      compared with previously reported spectra at lower field strengths. An increasing
      dominance of chemical shift effects over residual 14N-13C dipolar interactions is
      observed on the C alpha and C beta splittings with increasing field strength. A
      new structure is observed in the 25 ppm region of both samples. The spectra in
      this region were assigned by application of the depolarisation-repolarisation
      method. The assignment showed differences in the ordering of peaks between solid
      state and liquid state chemical shifts.

PMID- 1365719
TI  - Dipolar 31P NMR spectroscopy of crystalline inorganic phosphorus compounds.
AB  - The ability of the 90 degrees-t1-180 degrees pulse sequence to produce accurate
      dipole-dipole coupling information in solids is investigated. To this end, the
      experimental 31P spin echo decays are measured for eighteen crystalline
      phosphides and phosphorus chalcogenides and compared with simulations, based on
      the known internuclear distances in these compounds. The experimental results are
      generally found accurate in compounds where the dominant contribution to the
      dipole-dipole coupling arises from nuclei in structurally inequivalent sites with
      large chemical shift anisotropies. For this situation, the quantum mechanical
      "flip-flop" term in the dipolar Hamiltonian is suppressed and the dipole-dipole
      coupling is entirely heteronuclear in character. All of those compounds that do
      not obey this condition show accelerated spin echo decays due to a fractional
      contribution of the flip-flop term and possibly incomplete refocusing of chemical
      shift terms on the time scale of the experiment. The results confirm on an
      empirical basis that the spin echo NMR technique can provide accurate dipole
      dipole coupling information (and thus distance distributions) in disordered
      solids and glasses.

PMID- 1365720
TI  - Phosphorus-31 NMR studies of stabilized phosphorus ylids in the solid state.
AB  - Phosphorus-31 powder NMR spectra and high-resolution MAS spectra have been
      obtained for a number of stabilized phosphorus ylids under conditions of high
      power proton decoupling and cross-polarization. The 31P CP/MAS spectra are
      compared to those obtained from isotropic solutions. The variation of chemical
      shift anisotropy and of the principal components of the 31P chemical shift tensor
      determined from 31P powder NMR line shapes are discussed in terms of the relative
      importance of accepted valence bond resonance structures. The results indicate
      that the invariance of the isotropic chemical shift, delta iso, observed in
      previous 31P NMR investigations of phosphorus ylids in solution is due to
      fortuitous cancellation of opposing changes in the principal components, delta 11
      and delta 33, of the 31P chemical shift tensor. The 31P dipolar NMR powder
      spectrum of a typical stabilized ylid, (C6H5)3(31)P-13CHC(O)OCH2CH3, is analyzed
      in order to obtain the orientation of the 31P chemical shift tensor with respect
      to the 31P-13C alpha dipolar vector.

PMID- 1365721
TI  - Assignments of solid-state 13C resonances for polymorphs of cortisone acetate
      using shielding tensor components.
AB  - Carbon-13 CP/MAS spectra have been obtained for seven polymorphic and solvated
      forms of cortisone acetate. For signals in the high-frequency region, the
      spinning sideband manifolds of the spectra recorded under slow-spinning
      conditions have been analysed to obtain the shielding tensor components for the
      five resonances at the highest frequency. These show characteristic values for
      given types of carbon and have enabled assignments of the C5 and C22 signals to
      be made with some certainty, providing firm evidence of cross-over between the
      shifts for these carbons between different polymorphs. Assignments are suggested
      more tentatively for the resonances from C3, C11 and C20. Comparison of chemical
      shifts for those forms with published X-ray structures enables conclusions to be
      drawn regarding hydrogen bonding in the remaining forms. Hydrogen bonding induces
      a high-frequency change in the isotropic chemical shift of approximately 3 ppm.

PMID- 1365722
TI  - 1H NMR study of lithium D-lactate.
AB  - Polycrystalline D-lactic acid lithium salt [(R)-2-hydroxypropanoic acid lithium
      salt, lithium D-lactate] has been investigated by pulsed proton magnetic
      resonance methods between 77 and 300 K at 25 MHz. The main relaxation mechanism
      is methyl rotation; the motion is characterized by an activation energy Ea = 14.5
      +/- 0.5 kJ/mol and time factor tau 0 = (1.5 +/- 0.5) x 10(-13) s. The activation
      energy is higher than the potential barrier obtained by ESR and ENDOR techniques
      for methyl rotation in the lactate radical. The methyl rotation is also
      responsible for a reduction of the dipolar second moment. Below 100 K the
      reduction of the dipolar second moment is ascribed to quantum-mechanical
      tunneling; an excitation energy of 6.1 +/- 1 kJ/mol is derived from a
      contribution to the spin-lattice relaxation times from the tunneling.

PMID- 1365723
TI  - Proton relaxation NMR study of polycrystalline progesterone.
AB  - Polycrystalline progesterone (4-pregnene-3,20-dione, C21H30O2) has been
      investigated by proton NMR methods between 80 and 350 K. A reduction in dipolar
      second moment is ascribed to methyl group reorientation. Minima in the spin
      lattice relaxation time found in measurements at five frequencies from 7 to 200
      MHz are attributed to reorientation of two of the three methyl groups in each
      molecule, characterized by activation energy Ea = 10.9 +/- 0.8 kJ/mol and tau o =
      (2.3 +/- 0.2) x 10(-13) s. Additional relaxation at lower temperatures is
      attributed to reorientation of the third methyl group with Ea approximately 3.4
      kJ/mol. Measurements were also made of relaxation in the rotating frame.

PMID- 1365724
TI  - 27Al and 23Na double-rotation NMR of sodalites.
AB  - The 27Al NMR spectra of calcium tungstate aluminate sodalite (CAW),
      Ca8[Al12O24](WO4)2, and the 23Na NMR spectra of sodium aluminosilicate sodalites
      of general composition Na9[Si6Al6O24]A2 with A = B(OH)4- (SBS), SCN- (SRS) and A2
      = SO4(2-) (SSS), MoO4(2-) (SMS) have been measured using magic-angle spinning
      (MAS) and double-rotation (DOR) techniques. Rotor synchronized pulse excitation
      is applied in the DOR experiments. Dramatic line narrowing is observed in the DOR
      spectra of all samples. The 27Al DOR NMR spectra of CAW measured at 9.4 and 11.7
      T and spinning rates of 800-1150 Hz of the outer and 5 kHz of the inner rotor
      show seven sharp central lines accompanied by a manifold of spinning sidebands.
      These lines correspond to the seven crystallographically inequivalent Al sites of
      the CAW framework derived from X-ray structure analysis. From the difference of
      the line positions in the 9.4 and 11.7 T spectra the quadrupole coupling
      constant, QCC, quadrupole induced shift, sigma qs, and isotropic chemical shift,
      delta cs, of each Al site have been calculated. QCC values in the range of 5 to 9
      MHz are obtained which reflect the strong tetragonal distortion of the AlO4
      tetrahedra in CAW. delta cs shows only small changes in the range between 74.4
      and 77.2 ppm. A tentative assignment of all lines to the distinct Al sites is
      derived from the correlation between QCC and a "shear strain parameter"
      describing quantitatively the distortion of the AlO4 tetrahedra.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1365726
TI  - Study of a spin-3/2 system by a quadrupolar-echo sequence: suppression of
      spurious signals.
AB  - The density matrix describing the evolution of a spin-3/2 system excited by a
      quadrupolar-echo sequence consisting of two rf pulses in quadrature phase, (X)
      tau 2-(Y)-tau 4-[acquisition(y)], is calculated from the equilibrium state to the
      acquisition period. The interactions involved are the first-order quadrupolar
      interaction throughout the experiment and a local heteronuclear magnetic dipolar
      term between the two pulses and during the acquisition period. Three echoes, one
      due to a satellite transition at tau 4 = tau 2 and two due to the central
      transition at tau 4 = tau 2 and tau 4 = 3 tau 2, are predicted. They have similar
      expressions than those obtained with two rf pulses of the same phase, (X)-tau 2
      (X)-tau 4-[acquisition(y)], except the signs. Moreover, it is shown
      experimentally that a combination of these two sequences, namely: (X)-tau 2-(X)
      tau 4-[acquisition(y)]-recycle delay-(X)-tau 2-(-X)-tau 4-[acquisition(y)]
      recycle delay-(X)-tau 2-(Y)-tau 4-[acquisition(-y)]-recycle delay-(X)-tau 2-(-Y)
      tau 4-[acquisition(-y)]-recycle delay, cancels the spurious piezo-electric
      signals when studying a ferro-electric material in the single-crystal form.

PMID- 1365727
TI  - Observation of nitrogen-14, carbon-13 indirect spin-spin coupling in high
      resolution 13C CP/MAS spectra of solids.
AB  - The 13C CP/MAS NMR spectrum of [(n-C3H7)4N][Cd(SCN)3], 1, indicates the presence
      of three non-equivalent thiocyanate ligands, in agreement with the results of a
      recent single-crystal X-ray diffraction study. Examination of the 13C MAS line
      shapes allows direct measurement of the indirect spin-spin coupling constants,
      1J(14N, 13C) = 16 +/- 1 Hz and 2J(111/113Cd, 13C) = 75 +/- 5 Hz, for the unique N
      bonded thiocyanate ligand. This is the first reported measurement of 1J(14N, 13C)
      and 2J(111/113Cd, 13C) in the solid state. Possible reasons for the failure to
      observe 1J(14N, 13C) values in previous high-resolution 13C CP/MAS NMR studies
      are summarized.

PMID- 1365725
TI  - Multinuclear MAS NMR study of the microporous aluminophosphate AlPO4-17 and the
      related silicoaluminophosphate SAPO-17.
AB  - AlPO4-17 and SAPO-17 in their as-synthesized, calcined, and calcined and
      subsequently rehydrated forms have been studied by 27Al and 31P MAS NMR.
      Pronounced structural changes caused by template removal and rehydration can
      unambiguously be attributed to a change in the coordination number (on
      calcination: 5-->4, on rehydration/dehydration: 4<-->6) of part of the framework
      aluminium atoms. The different resonance lines can be assigned to
      crystallographically inequivalent sites present in the modified ERI framework.
      27Al quadrupolar coupling parameters of the two aluminium sites in the calcined
      AlPO4-17 (CQ = 4.4 MHz and 2.1 MHz) were determined by recording spectra at
      different field strengths. The isotropic chemical shifts were obtained from
      rotation sidebands of the (+/- 3/2, +/- 1/2) satellite transitions. 2D 27Al
      nutation MAS NMR was used to corroborate the line assignment for the as
      synthesized and the rehydrated AlPO4-17. By using 13C MAS NMR it was shown that
      the occluded template (cyclohexylamine) is present as ions. For the first time, a
      splitting of the 29Si NMR line caused by crystallographically inequivalent sites
      in a SAPO-type material is reported. The line splitting of 4.3 ppm is comparable
      with that observed for isostructural aluminosilicate erionite.

PMID- 1365728
TI  - 91Zr NMR characterisation of phases in transformation toughened zirconia.
AB  - A detailed 91Zr NMR investigation is presented of the five component (cubic,
      monoclinic, tetragonal, orthorhombic and delta) phase mixture in the
      transformation toughened engineering ceramic, magnesia-partially-stabilised
      zirconia (MgPSZ). The phases are distinguished on the basis of the quadrupole
      interaction displayed in the powder pattern of the 91Zr(1/2, -1/2) transition.
      This paper reports: (i) the first characterisation of the magnesia-fully
      stabilised cubic phase at the eutectic composition (13.5 mol% MgO); (ii) the
      observation of a poorly ordered tetragonal phase on fast cooling ZrO2 (9.3 mol%
      MgO) from the cubic phase field at 1720 degrees C, and the subsequent growth and
      ordering of the tetragonal phase precipitates due to further annealing; (iii) the
      observation of the (partial) transformation of the cubic phase to the ordered
      delta-phase (Mg2Zr5O12) on annealing MgPSZ at 1100 degrees C for 8 h; and (iv)
      the observation of the transformation of the tetragonal phase into the
      orthorhombic phase after cooling in liquid nitrogen, and the reverse
      transformation after heating to 600 degrees C.

PMID- 1365729
TI  - A multinuclear magnetic resonance examination of the mineral grandidierite.
      Identification of a 27Al resonance from a well-defined AlO5 site.
AB  - 11B, 27Al and 29Si magic angle spinning NMR results are reported for the
      boroaluminosilicate mineral grandidierite (Mg, Fe)Al3SiBO9. Three distinct
      aluminium sites are identified, two AlO6 and one AlO5. Despite overlap of the
      centrebands from these sites the use of three magnetic fields (9.4, 11.7 and 14.1
      T) allows unambiguous values for the isotropic chemical shift (delta iso),
      quadrupolar coupling constant (Cq) and quadrupolar asymmetry parameter (eta) to
      be deduced for each site. The NMR spectrum from the AlO5 site is simulated with
      parameters Cq = 8.7 +/- 0.1 MHz, eta = 0.95 +/- 0.05 and delta iso = 41 +/- 1 ppm
      which are compared to values from other well-defined AlO5 units.

PMID- 1365730
TI  - Selective saturation and inversion of multiple resonances in high-resolution
      solid-state 13C experiments using slow spinning CP/MAS and tailored DANTE pulse
      sequences.
AB  - Taking advantage of the long 13C T1 values generally encountered in solids,
      selective saturation and inversion of more than one resonance in 13C CP/MAS
      experiments can be achieved by sequentially applying several DANTE pulse
      sequences centered at different transmitter frequency offsets. A new selective
      saturation pulse sequence is introduced composed of a series of 90 degrees DANTE
      sequences separated by interrupted decoupling periods during which the selected
      resonance is destroyed. Applications of this method, including the simplification
      of the measurement of the principal values of the 13C chemical shift tensor under
      slow MAS conditions, are described. The determination of the aromaticity of coal
      using a relatively slow MAS rate is also described.

PMID- 1365731
TI  - Rotational frequencies of methyl group tunneling.
AB  - Methyl tunnel frequencies, measured at 4 K, are found to be 455 +/- 8 kHz in
      methyl malonamide and 496 +/- 8 kHz in methyl ethyl ketone. The first is
      unaffected by deuteration of the amide groups. Measurements of the temperature
      dependence of the spin lattice relaxation time are also reported for methyl
      malonamide and a further test is made of a previously reported correlation
      between tunnel frequency and the temperature of the T1 minimum. The measurements
      are in good agreement with the universal correlation curve.

PMID- 1365732
TI  - Magic-angle-spinning 31P NMR spectra of solid dihydrogen phosphates. Comparison
      of ordered and dynamically disordered compounds.
AB  - High-resolution 31P NMR spectra are reported for several dihydrogen phosphates in
      the solid state. Shielding tensor components were retrieved by analysis of the
      sideband intensities. The results, together with previously published data, can
      be grouped according to the presence and type of proton exchange occurring in the
      crystals. Static MH2PO4 samples (M = Na, Li) show a shielding anisotropy delta
      sigma of approximately 120 ppm. In the case of M = Cs (one static P-OH bond and
      two oxygens attached to "half" hydrogens on the average) delta sigma is smaller
      (approximately 75 ppm) and can be understood in terms of the accepted, proton
      exchange model. For highly disordered samples (M = K, NH4, Rb), where all four
      oxygens have nearby hydrogens with 50% occupancy, delta sigma is even smaller
      (approximately 30 ppm) but not zero. In the last-mentioned cases, 31P NMR
      information suggests that local PO4 environments may not have the symmetry that
      could be expected on the basis of the known crystal structures.

PMID- 1365733
TI  - Time-domain calculation of chemical exchange effects in the NMR spectra of
      rotating solids.
AB  - A simple method is described for the calculation of magic-angle-spinning (MAS)
      spectra of solids in the presence of chemical exchange. The method converges
      quickly, allowing rapid calculation of the spectra. Calculated spectra are given
      for molecular motion involving 2 and 6 sites.

PMID- 1365734
TI  - Solid-state 27Al NMR studies of aluminophosphate molecular sieves. Enhanced
      resolution by quadrupole nutation and double-rotation.
AB  - Solid-state 27Al NMR spectra of several aluminophosphate molecular sieves have
      been recorded with conventional magic-angle spinning (MAS), double-rotation (DOR)
      and quadrupole nutation with fast MAS. Enhanced resolution was obtained in the
      quadrupole nutation experiment at certain radiofrequency pulse strengths. This
      extra resolution can be comparable to that attainable using DOR, and does not
      introduce spinning sidebands.

PMID- 1365735
TI  - A bi-symmetric square wave Zeeman modulator for nuclear quadrupole resonance.
AB  - A simple circuit has been designed to generate a bi-symmetric square wave Zeeman
      modulation for the detection of nuclear quadrupole resonance. The square waveform
      not only provides an optimum result among bi-symmetric modulation waveforms, but
      also allows the observation of the Zeeman perturbed NQR powder pattern without
      the need for an extra external magnetic field.

PMID- 1365736
TI  - A versatile method for rotation-synchronised 2D exchange spectroscopy of solids.
AB  - A versatile, reliable, easy-to-use method to achieve rotor-synchronisation during
      the mixing time tau m in 2D magnetisation transfer experiments on rotating solids
      is shown. The limits of accuracy of the method are discussed and some examples of
      application are given. A full description of all technical details is provided.

PMID- 1365737
TI  - The chemical shift interaction under weak radio frequency pulses.
AB  - The chemical shift anisotropy of a nuclear spin system in a strong magnetic field
      can be comparable to the strength of the rf pulse (weak pulse condition). In this
      case, the commonly used assumption that the chemical shift interaction
      Hamiltonian in the duration of a rf pulse can be neglected is no longer
      effective. The rf response characteristics of a spin-1/2 system under a weak
      pulse condition is studied in detail. The relationships between the distortion of
      the chemical shift powder spectrum and the relative rf field amplitude under
      various conditions are given. The suppression of sidebands of a MAS spectrum is
      analysed as an example of solid multiple pulse experiments. The experimental
      results are in good agreement with computer simulations.

PMID- 1365739
TI  - Nuclear spin-lattice relaxation in transition metal compounds with local
      tetragonal symmetry.
AB  - We report on the various contributions to the total spin-lattice relaxation rate
      in metallic materials with local tetragonal symmetry. The analytical formulae are
      given in the tight-binding approximation. The calculations show the relation
      between various partial electron densities of states and corresponding
      contributions to the relaxation rates. The presented formulae can be used to
      compare theoretically calculated electron band structure parameters with those
      obtained from NMR spin-lattice relaxation time measurements.

PMID- 1365738
TI  - A study of tin dioxide and antimony tetroxide supported vanadium oxide catalysts
      by solid-state 51V and 1H NMR techniques.
AB  - A series of vanadia catalysts with various V2O5 loadings supported on SnO2 and
      alpha-Sb2O4 are investigated by the application of X-ray diffraction and solid
      state 51V and 1H NMR techniques. XRD results show no evidence for the formation
      of a crystalline vanadia phase on both supports. However, the 51V NMR spectra of
      the catalysts reveal the existence of two types of vanadia species on the surface
      of the support: one due to a dispersed vanadia phase at lower vanadia loadings
      and the other due to a crystalline vanadia phase at higher vanadium content. The
      quantity of the dispersed vanadia phase, however, depends on the nature of the
      support material. The 1H NMR results provide evidence for the existence or non
      existence of a metal oxide support interaction through the support surface
      hydroxyl groups.

PMID- 1365740
TI  - Quadrupole parameters of 11B in crystalline CaO.B2O3.
AB  - The quadrupole coupling constant (Qcc) and asymmetry parameter (eta) of 11B in
      crystalline CaO.B2O3 have been measured employing three different NQR and NMR
      methods: (1) 11B and 10B NQR; (2) 11B NQR and NMR; and (3) the 11B Zeeman NQR
      powder pattern. It is found that Qcc = 2594.3 +/- 0.5 kHz and eta = 0.515 +/-
      0.001 at 77 K, and Qcc = 2573.5 +/- 0.5 kHz and eta = 0.511 +/- 0.002 at 300 K.
      These values are in agreement with, but far more accurate than, values obtained
      from a fourth procedure: measurement of the second-order quadrupolar effects
      evident in the m = + 1/2<-->m = - 1/2 transition of the 11B NMR spectrum.

PMID- 1365741
TI  - 27Al satellite transition spectroscopy (SATRAS) of polycrystalline aluminum
      borate 9Al2O3.2B2O3.
AB  - 27Al NMR spectra of polycrystalline aluminum borate 9Al2O3.2B2O3 have been
      measured at 104, 130 and 156 MHz. The parameters of the quadrupole interaction
      and the isotropic chemical shifts have been obtained by fitting the CT/MAS
      pattern and consideration of the inner satellite transitions m = 3/2<-->1/2 and m
      = - 1/2<-->- 3/2. The gain in spectral resolution concerned with the observation
      of the MAS lines of the inner satellites leads to complete separation of the
      signals of AlO6, AlO5 and AlO4 polyhedra. Also signals of structural groups of
      one and the same coordination number can be distinguished. Experimental and
      theoretical lineshape calculations are compared.

PMID- 1365742
TI  - Sidebands in dynamic angle spinning (DAS) and double rotation (DOR) NMR.
AB  - A theory of dynamic angle spinning (DAS) and double rotation (DOR) NMR is
      described using average Hamiltonian and irreducible tensor methods. Sideband
      intensities in DAS and DOR spectra are analyzed by both the moment and Bessel
      function methods, and general formulae are derived. Results show that the DAS
      moments depend on the relative rotor phase between the first and the second
      evolution periods, whereas the second and third DOR moments are independent of
      the relative phase between the inner and outer rotors. Sideband intensities in
      DAS spectra also depend on the relative rotor phases between evolution at the
      first and second angles, as well as on the ratio of time spent at each angle.
      Sideband intensities and phases in DOR spectra are related to the relative rotor
      phases between the inner and outer rotors, and the sideband pattern is determined
      by the ratio of the inner and outer rotor spinning speeds. An inversion symmetry
      of the odd numbered DOR sidebands at the relative rotor phase gamma r = 0 degree,
      180 degrees permits the elimination of these sidebands. Finally, numerical
      simulations are implemented and shown to agree with experimental results.
      Quadrupolar parameters can therefore be recovered either by calculating the
      second and third moments or by simulating the sideband intensities and phases.

PMID- 1365744
TI  - [Adhesion capacity of Enterococcus faecium (SF 68) and Enterococcus faecalis to
      various substrates].
AB  - The author's studied the adherence ability of Enterococcus faecium SF 68 compared
      to that of Enterococcus faecalis IM 11f, on various substrates: vascular
      catheters and cardiac valves of rabbit, immunodepressed rats and diabetic rats.
      The bacterial adherence test was calculated by the number of bacteria adhered for
      microscopic field enlarged to 2000. The data obtained by scanning electron
      microscope SEM (Cambridge Stereoscan 150 MK2) revealed a different adherence
      action of the two germs on the various substrates. All the adherence tests showed
      a higher and uniform adherence activity of E. faecalis compared to that of E.
      faecium.

PMID- 1365743
TI  - [Pharmacologic interactions between quinolones and oral hypoglycemic agents. An
      experimental study on rabbits].
AB  - The association between antibiotics and oral hypoglycemic agents can determine
      various pharmacological interactions. The aim of our work has been to verify
      experimentally the eventual pharmacological interactions that may occur when some
      quinolones (nalidixic acid, ofloxacin, pefloxacin and sparfloxacin) are
      administered in association with oral hypoglycemic drugs (phenphormine and
      glibenclamide). Our results showed that ofloxacin, pefloxacin and sparfloxacin
      only at high dosages (not used in the human clinic) can increase the phenphormine
      and glibenclamide hypoglycemic effect. The nalidixic acid, just at therapeutic
      doses, is able to increase the hypoglycemic effect of the drugs studied.

PMID- 1365745
TI  - Activity of two benzofuran-imidazoles, IM/B/4-62 and IM/B/4-66, against
      experimental infections with Candida albicans and Trichophyton mentagrophytes.
AB  - The therapeutic activity of two new benzofuran-imidazoles, IM/B/4-62 and IM/B/4
      66, formulated as 1% cream, has been evaluated against Candida albicans and
      Trichophyton mentagrophytes by inducing experimental vaginal candidosis in female
      rats and dermatophytosis in female guinea pigs. Results of the treatment were
      compared with those obtained by the same therapeutic regimen carried out with
      bifonazole. IM/B/4-66 proved to possess superior antimycotic activity to that of
      IM/B/4-62 and similar to that of bifonazole in both infections. Nmaley vaginal
      candidosis was cured in all the treated in animals at 6 days post-inoculation and
      skin lesions were healed in 9 of 10 animals at 15 days after infection, with
      negative cultures from all the infected sites.

PMID- 1365746
TI  - Preliminary study to antituberculosis chemotherapy in a region of sub-Saharian
      Africa: annual risk of tuberculosis infection calculation and tuberculin survey.
AB  - A tuberculin survey was performed in Arua District (577,799 inhabitants, recent
      return of refugees from Zaire and Sudan) in 1987 prior to the implementation of
      antituberculosis Chemotherapy and Control Programme. 50 clusters (schools) of 30
      pupils each were selected in the 7 Counties by Sistematic Random Sampling. 1110
      students 10 year old without BCG vaccination scar were injected with 5 IU of PPD;
      1016 of them (more than 6% of the estimated district population of 10 year of
      age) came back after 72 hours for reading. 125 of them were positives (more than
      10 mm of induration). The Infection Rate detected was 1.23% +/- 0.19. Considering
      the infection rates found by the Ugandan National Surveys done in 1950 (2.6%) and
      in 1970 (2.3%), and the slight slope of the curve calculated on those values we
      have underestimated the real Infection Rate in the district. To avoid this bias
      we suggest to include schools in sampling (it is simple and cost-effective) only
      if the Student's population is likely to be representative of the general
      population.

PMID- 1365747
TI  - Effects of lipids on cancer therapy.
AB  - The fatty acid composition of cancer cell membranes can change substantially when
      the cells are exposed to different types of fat. Such change occurs when tumors
      are grown in animals fed high-fat diets that differ in degree of unsaturation or
      during culture in media supplemented with various fatty acids. Certain physical
      and functional properties of the membrane are modified when the polyunsaturated
      fatty acid content is increased, and the cells become more sensitive to
      hyperthermia or treatment with doxorubicin. These findings suggest a potential
      role for lipid nutrition in cancer therapy. By altering the properties of the
      membrane lipids, changes in the dietary fat intake may provide a new approach for
      enhancing the effectiveness of certain antineoplastic therapies.

PMID- 1365748
TI  - Report of the investigations carried out in the laboratory of pathology and
      bacteriology, Weltevreden, during the year 1889. VI. Polyneuritis in chickens.
      1890.

PMID- 1365749
TI  - Report of the investigations carried out in the laboratory of pathology and
      bacteriology, Weltevreden, during the year 1895. VI. Polyneuritis in chickens.
      New contributions to the etiology of the disease. 1896.

PMID- 1365750
TI  - Metabolic alkalosis in a patient with renal failure: role of antacids.
AB  - A 75-year-old patient with anuric renal failure developed a significant metabolic
      alkalosis thought to be due to the enteral absorption of "nonsystemic" antacid
      administered in large daily doses for prevention of recurrent peptic ulcer
      disease.

PMID- 1365751
TI  - Role of glycosylated vitamin B6 in human nutrition.
AB  - A study of lactating women consuming mixed diets showed that the quantity of
      dietary glycosylated vitamin B6 had little influence on the vitamin B6
      nutritional status of the mothers or their infants.

PMID- 1365752
TI  - Plasma dopa is unaffected by diet.
AB  - Significant amounts of bound 3,4-dihydroxyphenylalanine (DOPA), when present in
      dog food, did not affect plasma levels of DOPA or catecholamines in dogs. Thus,
      plasma DOPA is a useful index of activity of tyrosine hydroxylase, the rate
      limiting enzyme in catecholamine synthesis in these animals.

PMID- 1365753
TI  - Zinc and the regulation of vitamin B6 metabolism.
AB  - Pyridoxal kinase, a key enzyme in the formation of vitamin B6 coenzymes, requires
      a zinc-ATP complex as a substrate. Recent findings show that zinc-metallothionein
      facilitates the formation of the zinc-ATP complex. Thus, the concentration of
      zinc-metallothionein in tissues may serve in the regulation of vitamin B6
      metabolism.

PMID- 1365754
TI  - Aminocarnitine and related compounds as inhibitors of carnitine transferases:
      physiologic implications.
AB  - beta-Aminocarnitine and its N-acetyl and N-palmitoyl amides were examined as
      inhibitors of carnitine acetyltransferase, carnitine palmitoyltransferase, and of
      fatty-acid oxidation in whole animals, tissues, and hepatic microsomal systems.
      Results were consistent with subsequent findings that aminocarnitine and
      palmitoylcarnitine have significant antiketogenic and hypoglycemic effects in
      experimental animals.

PMID- 1365755
TI  - Vitamin C regulation of cartilage maturation.
AB  - Treatment of chondrocytes with vitamin C under defined conditions in cell culture
      initiates a differentiation program that closely mimics the normal maturation of
      cells in the growth plate of long bones.

PMID- 1365756
TI  - HIV-infection in the autopsy material (Hamburg 1984-1989).
AB  - 77 HIV-positive corpses were autopsied at the Institute of Forensic Medicine in
      Hamburg (in cooperation with the Bernhard-Nocht Institute) from August 1984 until
      September 31st, 1989. In the clinical autopsies (29 cases) the patients had
      always shown manifest AIDS symptoms, while 90% of the HIV-infected forensic
      autopsy cases had no AIDS symptoms during their lives and mostly died from drug
      overdose. Authors describe the clinical autopsy findings (Kaposi sarcoma,
      infections caused by opportunistic pathogenics), serological AIDS screen
      examinations, and the precautions applied during the autopsies. They also
      describe their own methods for the prevention of infection with reference to
      hygiene in the dissecting rooms.

PMID- 1365757
TI  - Ultrastructure of the developing myenteric plexus of chicken small intestine.
AB  - The present ultrastructural study established the main morphological events that
      occur during the myenteric plexus formation in the chicken duodenum from the 7th
      day of incubation (E7) up to hatching, with special attention to the appearance
      of different axon profiles and synaptic contacts. Transmission electron
      microscopy revealed that the compartmentalization of the enteric mesenchyma into
      outer and inner zones precedes the sequential morphological maturation of the
      crest derived cells during myenteric plexus formation. On E7, a slender neuropil
      was present in the migrating cell clusters, but all the crest derived cells were
      uniform. In the following stages, the neuronal and enteroglial cells were
      distinguishable. The first significant sign of neuronal maturation was the
      morphological heterogeneity in the vesicle population on E11. Progressive changes
      in the synaptogenesis were identified, and the axosomatic synapses were
      characteristic around hatching. On E18, a transient direct muscle-ganglion
      contact with the circular muscle layer was observed, in addition to the permanent
      ganglionar contact to the longitudinal layer of the muscularis externa.

PMID- 1365758
TI  - On the alteration of pulmonary arteries in different experimental pneumoconioses.
AB  - CFY rats were treated intratracheally on one occasion with 60 mg of DQ12 quartz,
      illite (aluminosilicate) and enargite (dead rocks of a metal mine) suspended in 1
      ml physiological saline. After a year, the structure of the pulmonary arterial
      system of pneumoconiotic rats was investigated by means of injection-corrosion
      cast and gelatin-India ink samples in thick preparations. In the identically
      treated animals, blood-gas analysis was made of samples of femoral arteries
      before and after intravenous treatment with noradrenaline and acetylcholine (40
      40 micrograms/b.w.) under sodium pentobarbital narcosis. It has been stated that
      in focal alterations characteristic of different types of pneumoconioses,
      arborisation of the pulmonary arteries is and a newly developed and/or
      transformed vascular structure can be observed around the foci. In
      pneumonoconiotic lungs, arteriovenous shunts are more frequent. The authors
      assumed some connection between the vascularization of foci and the progression
      of the fibrotic process: richer vascularization around and inside the foci was
      accompanied by significant fibrosis. The blood-gas values suggested compensated
      respiratory acidosis. In the examined pneumoconioses, the effect of vasoactive
      substances - in terms of blood-gas values - had not changed significantly.

PMID- 1365759
TI  - Determination of G1-S-G2 phase fraction ratios of tumour subpopulations from DNA
      histograms.
AB  - Authors describe a new mathematical approach based on mixture decomposition and
      maximum likelihood method for the determination of subpopulations and G1-S-G2
      phase fraction ratios in aneuploid, multiploid DNA histograms. A special computer
      routine was developed for this purpose (DAHSY). The present study relates to DNA
      histograms obtained by a Leitz Miamed DNA TV image analyser system. Altogether 23
      normal, 14 dysplastic and 28 tumours Feulgen stained gastric imprint smears were
      measured. In addition to determination of subpopulations and G1-S-G2 phase
      fraction ratios, the authors also performed a morphometric analysis of Feulgen
      stained nuclei and determined the values of 5c exceeding rate (5cER) and the 2c
      deviation index (2cDI). More than one subpopulation were found only in tumours.
      The usual G1-S-G2 phase fraction rates in normal gastric smears were 85.5%,
      9.04%, 4.9%, in dysplastic cases 74%, 15.4%, 10.2% and in tumours 53.8%, 22.9%,
      18.8%. Significance of the differences were calculated by the T-test. The G1
      phase fraction ratio clearly discriminates the malignant lesions from all others.
      The S+G2 phase fraction ratio, however, distinguishes the normal cases from the
      dysplastic ones. The 2cDi and 5cEr could support a multivariate diagnostic
      system. The cell nucleus area was found also to be of diagnostic value.

PMID- 1365760
TI  - Chronic intestinal lymphocytic microphlebitis.
AB  - The authors report two cases of a peculiar microphlebitis of the intestines,
      similar to that described by Saraga and Costa quite recently [5]. The patients
      had undergone hemicolectomy because of evolving ileus caused by cecal polyps or
      lipohyperplasia, respectively. Pseudomembranous-ulcerative inflammation of the
      cecum and variously intense lymphocytic infiltrates of numerous small submucosal
      veins and venules of the intestines were found in both cases. Thrombosis occurred
      very rarely in the affected vessels, although sometimes it was found in deeper
      and larger veins. Arteries, lymphatics, mesenterial veins and lymph nodes were
      normal. Parts of the distal ileum and ascending colon displayed the phlebitic
      changes without mucosal alterations. The authors hypothesize that it was not the
      abnormal local circulation, but some hitherto not fully clarified immunological
      disorder that resulted in the disease. In contrast to the claim of Saraga and
      Costa [5], it is suggested that thrombosis of the small veins does not have a
      significant role in the development of the lesions, but a complex process that
      includes the entry of antigens via the altered mucosa followed by an immunogenic
      inflammatory response of the small veins is responsible for the pathogenesis.

PMID- 1365761
TI  - Cardiac changes in rheumatoid arthritis.
AB  - We reviewed the autopsy material of 169 patients with rheumatoid arthritis (RA)
      and studied the cardiac changes is these patients. Systemic vasculitis was
      observed in 26 cases (15.38%) among 169 patients with RA. In 17 cases (10%) we
      found vasculitis of the subepicardial and/or intramural coronary vessels.
      Coronary arteritis or arteriolotis has led to multifocal small, and/or large
      myocardial infarctions in 10 cases (5.9%) and was the cause of progressive
      cardiac insufficiency, the direct cause of death. Multifocal circumscribed
      myocardial infarction reported in rheumatoid disease. In 8 cases rheumatoid
      nodules were found in the myocardium, 3 of them related to vasculitis. We suggest
      that rheumatoid nodules are the most severe form of necrotizing granulomatous
      vasculitis. Pathognomic nodular rheumatoid pericarditis was seen in 3 cases and
      diffuse rheumatoid pericarditis in another case. Pathognomic nodular valvulitis
      was found in 7 cases. Rheumatoid nodules localized to the epi-, myo-, or
      endocardium were observed on 9 patients. Generalized secondary amyloidosis was
      observed in 32 (18.93%) of the 169 patients with RA. Secondary amyloidosis was
      prevalent in the heart in 29 of 32 cases (relative frequency: 90.62%).

PMID- 1365762
TI  - The diverse modification of N-butyl-N-(4-hydroxybutyl) nitrosamine induced
      carcinogenesis in urinary bladder by dibromodulcitol and dianhydrodulcitol.
AB  - The effects of intravesical therapy with adriamycin, 1.6-dibromo-1.6
      dideoxydulcitol (DBD) or with 1.6-dianhydrodulcitol (DAD) on bladder
      carcinogenesis were investigated in rats. To induce premalignant lesions in the
      urinary bladder female Sprague-Dawley rats received 0.05% N-butyl-N-(4
      hydroxybutyl) nitrosamine (BBN) in their drinking water for 4 weeks and then post
      treated intravesically with one of the antitumor drugs and examined once a week
      for 3 months. These antitumor drugs in healthy rats (i.e. without the pre
      administration of BBN) did not cause any significant morphological changes in the
      urinary bladder after intravesical application once a week for 3 months. In the
      applied dose BBN alone induced only premalignant lesions in the urinary bladder.
      However, neoplastic lesions occurred in the groups treated with BBN and
      adriamycin (9 papillomas and 3 carcinomas in 14 animals). Similarly intravesical
      application of DBD after BBN administration resulted 5 carcinomas among the 11
      animals. On the contrary no urinary bladder tumor was found in the animals
      treated with BBN and DAD. As DAD is one of the conversion products of DBD it is
      conceivable that the difference between DBD and DAD action may be due to the
      formation of other solvolytic product from DBD than DAD.

PMID- 1365763
TI  - Scanning electron microscopic (SEM) examination of structures which supply
      subcapsular and midcortical region postglomerular microcirculation in sheep
      kidney.
AB  - Sheep kidneys were injected with polyester crystic (Dewilux 511-0196) and three
      dimensional forms of the structure forming the postglomerular microcirculation
      were examined by scanning electron microscope. During the examination of the
      afferent and efferent arterioles, a glomerulus with double efferent arterioles
      were examined and microdiverticular structures were observed in the terminal end
      of peritubular capillary plexus. It is concluded that these structures widen the
      surface area of the capillaries as a result of which diffusion across the
      capillary bed is facilitated.

PMID- 1365764
TI  - Ultrastructure of normal and hepatitis virus infected human and chimpanzee liver:
      similarities and differences.
AB  - Ultrastructure of liver biopsy specimens obtained from normal and hepatitis B
      (HBV) and hepatitis C virus (HCV) infected livers of patients and chimpanzees
      were compared. Nuclear alterations (glycogen particles, nuclear bodies,
      "vermicellar bodies", etc.), intracytoplasmic crystalloid inclusions were
      observed before and after the HBV and HCV infections both in human and chimpanzee
      hepatocytes, however, some of them were more common during the viral infection.
      Extreme endoplasmic reticulum dilatation characterized the human, while the
      presence of membranous cytoplasmic inclusions the hepatocytes of chimpanzees
      during HCV infection. Interferon-associated membrane alterations were noted
      during acute or chronic hepatitis, however, in slightly different forms in humans
      and chimpanzees. Data suggest to be precautions in the interpretation of the
      ultrastructural alteration observed in different species even to be so closely
      related as humans and chimpanzees especially during infection with hepatotropic
      viruses.

PMID- 1365765
TI  - Proliferating cell nuclear antigen (PCNA) expression in childhood lymphomas.
AB  - Paraffin sections from 21 cases of Hodgkin's disease (HD) and 28 cases (26 high
      grade and 2 low-grade) of non-Hodgkin's lymphomas (NHL) occurring in childhood
      were examined for the presence of proliferating cell nuclear antigen using an
      anti-PCNA antibody. All cases of HD and NHL showed PCNA reactivity. In HD 50.9%
      (mean value) of Hodgkin and Reed-Sternberg (HRS) cells were PCNA positive and
      judged to be proliferating. PCNA reactivity was also found in a varying number of
      cells of the background population in HD (mean value = 11.7%). In NHL 61.2% (mean
      value) of cells were PCNA positive. In the 26 high grade tumours 63.6% (mean
      value) of cells were PCNA positive while only 32% (mean value) of cells were PCNA
      positive in the 2 low-grade tumours. Our results show that the proliferation rate
      of tumour cells in high-grade NHL is higher than those of tumour cells in low
      grade NHL and HRS cells in HD. Moreover, we found a considerable variation of
      proliferation rate among individual cases of HD (range 31%-68%) of NHL (range 31%
      78%). This suggests that PCNA assessment can help in the individual approach of
      the proliferation rate of each tumour, and, in conjunction with other parameters
      of the cell proliferation, could be useful for the understanding of the
      biological behavior of childhood lymphomas.

PMID- 1365766
TI  - Expression of the Epstein-Barr virus encoded latent membrane protein in tumor
      cells of Hodgkin's disease occurring in childhood.
AB  - Paraffin sections from 21 cases of Hodgkin's disease (HD), 28 cases of non
      Hodgkin's lymphomas (NHL) and 34 cases of non-specific reactive lymphadenitides
      occurring in childhood were examined for the presence of the Epstein-Barr Virus
      (EBV)-encoded Latent Membrane Protein (LMP) using a double layer
      immunohistochemical method. LMP was detected in 12/21 (57%) cases of HD but not
      in NHL or reactive lymph nodes. LMP reactivity was restricted to Reed-Sternberg
      and Hodgkin's (HRS) cells in 4 of 9 (45%) cases of nodular sclerosis (NS), 6 of 9
      (66%) cases of mixed cellularity (MC) and 2 of 2 (100%) cases of lymphocyte
      depletion (LD) while it was undetectable in the single case of lymphocyte
      predominance (LD) subtype. These results provide further evidence for an
      association between EBV and Hodgkin's disease, and they show that LMP expression
      occurs more frequently in the clinically more aggressive subtypes of HD.
      Furthermore, in view of the in vitro transforming potential of the LMP protein,
      the exclusive immunolocalization of LMP in HRS cells, suggests that EBV may be
      involved in the pathogenesis of a proportion of cases of HD.

PMID- 1365768
TI  - Absence of HTLV-I DNA sequences in cutaneous T-cell lymphoma/mycosis fungoides.
AB  - Recently, the presence of deleted forms of the HTLV-I provirus was described in 6
      out of 6 cases of CTCL. We investigated whether the presence of these viral
      genomes could be verified in 20 patients with CTCL using the polymerase chain
      reaction (PCR) and Southern blot analysis. Only one of the 20 cases showed a band
      corresponding to the pX region of HTLV-I. These data indicate that in the
      majority of CTCL cases, sequences closely related to HTLV-I are not present, or
      their copy number is below the limit of detection employed in this study.

PMID- 1365767
TI  - Electron-microscopic studies on the effect of calcium pantothenate upon rat liver
      and locally irradiated epidermis.
AB  - Calcium pantothenate was administered to Wistar rats in a dose of 180 mg/day/rat
      for 42 days, in order to investigate its effect upon the ultrastructure of the
      epidermis locally irradiated with a dose of 600 rep and upon partly
      hepatectomized liver and locally irradiated epidermis, as compared to control.
      The resulting data have revealed that calcium pantothenate is metabolized without
      entailing ultrastructural changes. Both liver and epidermis appear to be
      protected by calcium pantothenate, which greatly diminishes or even cancels the
      display of irradiation-induced negative effects. The changes brought about by
      irradiation are throughly presented and the subcellular mechanisms providing the
      radioprotection of epidermis and liver are accurately defined.

PMID- 1365769
TI  - Lectin staining studies on follicular atresia in house rat (Rattus rattus).
AB  - Topographic distribution of terminal and intercalary carbohydrate moieties were
      studied using horseradish peroxidase conjugated Glycine max (GMA), Arachis
      hypogea (PNA), Lotus tetragonolobus (LTA), Bandirarea simplicifolia (BSA), and
      Dolichos biflorus (DBA) agglutinins. N-Gal NAc, alpha-D-Gal, alpha-L-Fuc, D-Gal
      (beta-1-3)-D-Gal NAc, and alpha-beta-D Gal NAc linked glyco-conjugates were
      exposed during follicular atresia in oocyte, zona pellucida and granulosa cells.
      Theca interna and interstitial gland tissue revealed homology in lectin binding.

PMID- 1365770
TI  - DNASK--a new image analysis module for TV image cytometry.
AB  - The DNASK is a PC-based image analysis module for quantitative cytological and
      histological examinations on Feulgen-Schiff preparations. The module consists of
      a frame grabber, a CCD black and white video camera and the DNASK software
      package which can be incorporated in an IBM compatible PC-AT joining to a
      standard pathological research photo microscope. The use of 386 IBM AT systems
      leads to significant decrease of the measurement's time. Mono- or color VGA
      graphics card should be used. The resolution of the images is 512 x 512 pixels
      and 256 gray values. The image caption is made in less than 0.5 second, the
      measurement of a cell nuclei (18 parameters) takes less, than 5 seconds (IBM AT
      286). The camera is a standard CCD one. The microscope should be a good quality,
      modern microscope with built-in light source, however, the application of voltage
      stabiliser is strongly recommended. The software is able to measure the
      parameters mostly used and suggested in the international literature: 15 morpho-
      and densitometric parameters of the cell nuclei 6 DNA histogram parameters of the
      measured case, like DNA Index, 2c deviation Index, 5c exceeding rate, G1-S-G2
      phase fraction ratio. The system supports the grouping of the measured cases and
      at the end of a study results of the single measurements can be collected and
      summarized in an ASCII file, which is readable by major statistical
      programpackages. The DNASK has a special graphical user interface for the control
      of the program.

PMID- 1365771
TI  - Influence of chromatin condensation on the absorption spectra of nuclei stained
      with toluidine blue.
AB  - To study the influence of chromatin condensation on the absorption spectra of
      nuclei stained with toluidine blue, DNA staining methods--which favour or prevent
      dye polymerization--were applied to the imprints of rat tissues that differed
      greatly in the density of chromatin packing. It is stated that all factors
      promoting dye polymerization cause a left shift of the spectra while the factors
      preventing it, a right one. It was found that condensation of the chromatin can
      raise prerequisites that both enhance and hinder polymerization, and that the
      final result depends on the staining method, the manner of chromatin folding, and
      the density of its packing.

PMID- 1365772
TI  - A new computerized polarization--microscopic method for the demonstration of
      collagen fibers.
AB  - A new computerized polarization microscopic method was developed for objective,
      quick quantitative analysis of anisotropic structures. The paper presents the
      technology on collagen fibers of kidney and liver preparations. According to the
      observations the birefringence of one fiber can be characterized not by a single
      number as it is accepted generally but by a series of data. It suggests that the
      process of compensation is gradual. One of the explanations of this fact might be
      that the collagen fibers are inhomogeneous at submicroscopic level. With regard
      to this assumption, first several birefringent capillary basement membranes of a
      whole glomerulum were measured simultaneously. In this case, the individual
      capillaries showed nearly the same retardation. Second, portal zones of normal
      and cirrhotic livers as functional units were analyzed simultaneously. In the
      latter case the individual fibers show different birefringence. Comparing the
      results obtained by their technique with the data of the classic measuring method
      authors found similarity that proved its validity. Data suggest that the new
      method seems to be useful in experimental and diagnostic pathology.

PMID- 1365773
TI  - Generalized secondary amyloidosis in rheumatoid arthritis.
AB  - The autopsy material of 215 RA patients was studied to determine 1) the frequency
      of generalized secondary amyloidosis (GSA), 2) the frequency and extent of
      amyloid deposits in various organs, 3) the chronological succession of amyloid
      deposition in various organs. The tissue specimens were fixed in 8% formaldehyde
      solution and embedded in paraffin. Serial sections were cut and stained with HE
      and Congo-red according to Romhanyi, without alcoholic differentiation. The
      average amount of amyloid deposition in various organs was determined on a 0 to 4
      plus scale. Thirty-seven cases were found to contain stainable amyloid (17.2%).
      The frequency and degree of amyloid deposition in different organs of RA cases
      with GSA are summarized in the following table. [table: see text] The frequency
      and extent of amyloid deposits in various organs may be linked to the ratio of
      cardiac output distributed over a different tissue mass. In conclusion, the
      tissues and organs often showing high quantities of amyloid are the sites where
      the deposits begin. Where deposits are infrequent or of low quantity deposits
      develop later. Amyloid deposits early in the wall of blood vessels, first of all
      within the GI tract, heart, kidneys, thyroid gland, spleen and the adrenal
      glands.

PMID- 1365774
TI  - Etiological study on isolated proximal intercalary type of congenital limb
      deficiency in Hungary, 1975-1984.
AB  - A population-based and validated data set of 14 cases with isolated proximal
      intercalary type of congenital limb deficiency born in Hungary between 1975-84
      was evaluated. Two cases had phocomelia of upper limbs, while 12 cases were
      affected with classical intercalary defects mainly in femurs. Of 14 cases, 13 had
      unimelic manifestation and both sexes were equally affected. The intrauterine
      growth retardation, the excess of second birth order, a higher rate of acute
      maternal disorder of the respiratory system and the lack of familial cluster are
      noteworthy. The vascular disruption hypothesis seems to be the most plausible
      explanation for the origin of isolated proximal intercalary defects.

PMID- 1365775
TI  - Morphological changes of cultured rat hepatocytes exposed to methylglyoxal.
      Calcium-independence of injury.
AB  - Methylglyoxal-induced morphological changes were studied in cultured rat
      hepatocytes. Hepatocytes incubated either in the presence or absence of 2.5 mM
      Ca2+ were injured by 10 mM methylglyoxal to a similar extent, while 1 mM of the
      alpha-oxoaldehyde caused a moderate damage only in the absence of Ca2+. In the
      absence of Ca2+, however, hepatocytes were already injured, even without the
      presence of methylglyoxal hepatotoxicity proceeds independently of the Ca2+
      influx.

PMID- 1365777
TI  - [Treatment of crural varicose with topical dressings of "synthetic skin"].
AB  - In Dermatological Department of the Lublin Medical Academy 22 patients with
      crural varicose ulcerations have been treated with topical Codogard dressings.
      Before this treatment the patients were given some antiinflammatory and
      vasodilatatory drugs. The treatment lasted from 4 to 12 weeks (mean 6). In 9
      patients complete healing was reported (they had small ulcerations). In 10 cases
      the improvement was evident, in 2 cases the treatment was discontinued. The
      obtained results point to clinical usefulness of Codogard, as the drug is easy to
      be applied and it may play a significant role to outpatients.

PMID- 1365776
TI  - Primary malignant tumours associated with thyroid carcinoma in autopsy material.
AB  - In our Department 37,504 autopsies were performed in the last 30 years. Double
      multiple primary malignant tumours were found in 385 cases (4.2% of the cases
      with malignant tumours). In thyroid cancer cases, tumours of other organs were
      more frequent (20 cases, 22.7%), and these tumour associations were observed
      mainly simultaneously; there were no significant sex differences. In the more
      frequent synchronous cases, the thyroid cancer was a tumour only accessory to
      other malignancies; in the rarer metachronous cases, the thyroid cancer was
      secondary to postoperative irradiation of the first tumour (4 of 5 cases).
      Thyroid cancers were seen most frequently together with lung, breast and
      digestive system tumours; there was no special association recognizable to
      certain other malignancies. Follicular carcinoma was more frequent among the
      cancers associated with another tumour (12 of 20 cases), while in general the
      papillary was the most frequent type (48 of 88 cases).

PMID- 1365778
TI  - Comparison between radiographic image of mesiodens and its real position and
      morphology.

PMID- 1365779
TI  - The influence of monoparel-selenium on the body temperature, haematopoietic
      system, and functional state of the liver in rabbits.

PMID- 1365780
TI  - The comparative evaluation of delta-aminolaevulinic acid and creatinine levels in
      the urine of children from Swidnik and Bystrzyca Stara areas as a manifestation
      of exposure to lead compounds.

PMID- 1365781
TI  - The level of delta-aminolaevulinic acid and creatinine in the urine of children
      and youth from the primary school in Bystrzyca Stara (the Lublin province).

PMID- 1365782
TI  - Histological appreciation of the stomach after the application of thiophosphoric
      acid derivatives of Chelidonium majus L. (Ukrain) alkaloids.

PMID- 1365783
TI  - [Studies of susceptibility to antibiotics in strains of E. coli isolated from
      urine in the years 1986-1990].
AB  - From 1986 to 1990 research was conducted on E. coli strains isolated from
      patients with clinical symptoms of urinary tract infection. The paper-disk-plate
      technique was applied to determine their susceptibility to ampicillin,
      carbenicillin, azlocillin, cefamandole, cefotaxime, ceftriaxone, ceftazidime,
      cefoperazone, amikacin, netilmicin, gentamycin, vibramycin, and colistin.
      According to the authors' results the efficacy of ampicillin against the examined
      strains is as low as 3.4%. Aminoglycosides were traditionally recommended in
      therapy of urinary tract infections. Our research proves amikacin and netilmicin
      to be more effective against E. coli than gentamycin. The third-generation
      cephalosporins are recommended as alternative to aminoglycosides, especially
      since they are proved to be non-nephrotoxic. According to the results of the
      authors' research ceftazidime, cefotaxime and particularly ceftriaxone show the
      highest activity against the used strains of E. coli.

PMID- 1365784
TI  - [Susceptibility to nitrofurantoin, biseptol and nalidixic acid of E. coli strains
      isolated from urine in the years 1983-1990].
AB  - The group of microorganisms causing urinary tract infections includes the
      Enterobacteriaceae family, particularly E. coli, being the most commonly detected
      etiologic factor of the above infections. Research was conducted from 1983 to
      1990 on 1102 E. coli strains isolated from patients with clinical diagnosis of
      urinary tract infection. Susceptibility of the bacteria to nitrofurantoin,
      Biseptol and nalidixic acid was determined by application of the paper-disk-
      plate technique. The percentage of nitrofurantoin susceptible strains during the
      time period of research remained on the low level of 6-20%. The susceptibility of
      the strains isolated from 1983 to 1987 to Biseptol was also low, 0-11%, however,
      in later years (1988-1990) the gradual increase of susceptibility was observed,
      reaching the level of 35% in 1990. The most active of the used chemotherapeutics
      turned out to be nalidixic acid proven to be effective against 34.3-56.3% of E.
      coli strains.

PMID- 1365785
TI  - Nasal-sinusal polyps in the picture of combined radiological-endoscopic
      technique.

PMID- 1365786
TI  - The influence of glucose load on gamma-glutamyl-transpeptidase (GGTP) activity in
      the serum of patients with acute disturbances of the cerebral circulation.

PMID- 1365787
TI  - The influence of glucose loading on the content of free fatty acids in blood of
      patients with cerebral infarction and with acute transient circulatory cerebral
      insufficiency.

PMID- 1365788
TI  - [The collagen content of the lining of the basilar artery of rabbits].

PMID- 1365789
TI  - The effect of piracetam on the content of glucose in the blood of patients with
      cerebral infarction at the very early stage of the illness.

PMID- 1365790
TI  - The level of antibodies against cytomegalia virus in the workers of probationary
      and infectious diseases departments.

PMID- 1365791
TI  - [Dr. Piotr Borsukiewicz--one of the pleiad of physicians in Lublin (the 75th
      anniversary of his death)].
AB  - Seventy years have passed since the death of dr Piotr Borsukiewicz. He spent 9
      out of his 22 years of work in Lublin (1909-1918) being the head of the
      paediatric hospital (1911-1918), the member of the Lublin Medical Society, the
      president and vice president of some other public service organizations and
      inscribed himself in letters of gold in the history of medicine and people of
      Lublin. He worked and lived in the difficult years of two wars (1904-1905 and
      1914-1918), the rapid development of medical sciences and the separation of
      medical specialties. His diligence, loyalty to the Hippocratic code and the
      instructions of dr W. Bieganski as well as to the patriotic dictates resulted in
      the union of the meaning of his own existence with the deep belief in man and the
      favourite work as a physician. Helping the poor and those in need he contracted
      spotted fever but belittled his complaints and died on April 12, 1918 in Lublin.
      He left us the special patterns of the ideal medical care which are still alive
      today, so non omnis moriar.

PMID- 1365792
TI  - [Gram-negative bacteria isolated from mucous membranes of the nose and pharynx in
      mixed infections. The characteristics of their drug-resistance].

PMID- 1365793
TI  - The characteristics of drug-resistance of bacteria isolated from external
      acoustic meatus during infections of the middle ear.

PMID- 1365794
TI  - Spleen morphometry in Cercopithecus aethiops.

PMID- 1365795
TI  - Pharmacological properties of ametantrone.

PMID- 1365796
TI  - [Lysosomal enzyme activity of the lining of the basilar artery of the pig].

PMID- 1365797
TI  - Arterial blood hypertension in the aspect of some risk factors.

PMID- 1365798
TI  - [Examination of gastric juice in animals fed with fodder containing power plant
      ashes and loess dusts].
AB  - Normal metabolism, regulation of stimulation and checking of electrolyte
      secretion in the gastric juice depend on the way of feeding and its nutritional
      ingredients. Feeding experimental animals with fodder containing power plant
      ashes or loess dusts causes a change in the gastric juice reaction, thus
      resulting in a different assimilation of elements contained in the fodder. There
      was shown an increase of some elements content (Mg, Na, Cu, Fe), a decrease in
      the content of some others (Pb,Zn) in the gastric juice and a positive tendency
      for blocking by calcium ions of heavy metals contained in the fodder by the
      mucous membrane of the stomach.

PMID- 1365799
TI  - Thirty years after the creation of cryoophthalmology.
AB  - Low temperatures in ophthalmology were first applied in the end of the previous
      century. However, those experiments were not sufficiently documented and were not
      widely used. So the report concerning the Krwawicz (6) method of the cataract
      cryoextraction published in 1960 is commonly treated as the beginning of the
      modern cryoophthalmology. This extremely effective and simple method very quickly
      met with approbation and became commonly applied. After the surgical exposure of
      the opacificated lens the copper cryoextractor frozen to about -72 degrees C was
      applied to it. The deep lens freezing to the apparatus occurred enclosing the
      subcapsular masses. Then the fibres of Zinn ligament were broken and the cataract
      was gently removed. Due to its safety and the lack of complications the above
      technique led the real revolution in the cataract surgery. Its was compared to
      the epochal contribution of Daviel who was the first to remove the lens in 1774.
      Its importance however, was not just limited to the improvement of the surgical
      technique. Thanks to the cryoextraction the possibilities of the low temperature
      application in medicine were noticed. In a short period of time low temperatures
      began to be used in some other specialties: laryngology, neurosurgery, oncology,
      etc. It was found out that great number of the eye diseases could be treated in
      that way, including viral keratitis, haemorrhages to the vitreous, glaucoma, etc.
      The gradually gained experience gave rise to the new branch of ophthalmology
      called cryoophthalmology.

PMID- 1365800
TI  - Optimal nursing care provided to the neurosurgical patients with disturbed higher
      cortical functions.

PMID- 1365801
TI  - [The lateral root of the median nerve and its fascicles in the human].
AB  - The studies were carried out bilaterally on bodies of 51 males and 52 females who
      died at the age from 1 day to 87 years. There was shown a great individual
      variability and asymmetry regarding both the thickness of the lateral root of the
      median nerve, the number of fascicles, the size of the cross-section area of
      fascicles and the index of the fascicles area.

PMID- 1365802
TI  - [Acid-base equilibrium of hydrazone derivatives 4-R-3R1-thazol-2-one. I.
      Ionization constants of alpha-methyl-beta-(4-R-thiazol-2-yl)- and alpha-methyl
      beta-(4-R-3-R1-thiazol-2-ylidene)-hydrazides of benzoic acid].
AB  - The ionization constants of the following compounds have been determined
      spectrophotometrically in aqueous solution: [table: see text] The comparison of
      absorption spectra in UV and pK values of the compounds being described in this
      work and of the derivatives having a thiazole or thiazoline structure which were
      studied previously let us suggest that in the II-H neutral molecule and the I-H
      and II-H mono-anion the thiazole form prevails while in the case of the I-H
      neutral molecule the thiazoline form is more probable.

PMID- 1365803
TI  - Some features of the internal structure of the root of the brachial plexus from
      C5 in post-fetal life in man.

PMID- 1365804
TI  - Fascicular structure of the root of the brachial plexus from C6 in man.

PMID- 1365805
TI  - [Fascicular structure of the root of the brachial plexus from C7 in post-fetal
      life in man].
AB  - The thickness of the root of the brachial plexus coming from C7, the number of
      its fascicles, the size and the index of their cross-section area have been
      examined bilaterally on the bodies of 69 dead men of both sexes. During the
      postnatal life there increased: thickness of the root--over 3.4 times, the cross
      section area of root's fascicles--2.9 times, the number of fascicles--by about
      60%. In the same time the index of fascicles cross-section area decreased over
      18%. The above changes took place mostly up to 22nd year of life.

PMID- 1365806
TI  - The evaluation of medical college students' preparation to propagate health
      education.
AB  - The propagation of health education is within the range of nurses' professional
      duties. It necessitates the use of specific methods and techniques of work.
      "Inasmuch as the doctor treats, it is the nurse who creates best possible
      conditions for recovering and keeping health conditions permitting treatment or
      prevention" (3, 12). The increased level of general education among people and
      changes in modern nursing make the nurse face new tasks in her work. Nurse must
      be qualified in the field of health education if she works in the out-patient
      medical service as well as in hospital. She must be able to convince people about
      the necessity of changing life style, harmful and improper habits. The
      fulfillment of this difficult, yet important task may change patient's and his
      family's health habits and behaviour. So, nowadays the nurse must combine two
      functions: health-nursing called health-missioner's work with sick-nursing (1, 4,
      9). Work in the field of health education requires high level of professional
      knowledge, skills, methods, recognition of educational and sanitary needs of a
      social group, personal direct influence based on proper social attitude, which is
      very important (10, 11). Health education is best and most effectively propagated
      in situations of individual contact with the patient (7). Patients seeking help
      in medical service institutions are interested in their health and want to do
      something in the field (8). The analysis of nurse's and midwife's positions shows
      that work in out-patient health service and in hospital offers a close contact
      with the patient and his environment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1365807
TI  - Health condition of a specified rural area youth with regard to certain hygienic
      habits and civilization harmfulness.

PMID- 1365808
TI  - [Examination of the pancreas using various imaging methods].
AB  - After presenting contemporary employed various imaging methods, the comparative
      evaluation of Ultrasonography and CT in examination of pancreas lesions is
      discussed. It was stressed that techniques mentioned above give comparable good
      results and that they are complementary. The authors pointed out that US is the
      first technique of examination of the gland and in many cases it enables the
      proper diagnosis, whereas CT is used when the result of US examination is
      doubtful. Standard scans were performed and interpreted in each patient before
      using US and CT examination. In cases still obscure a biopsy is indicated. The
      frequency of pancreas visualization is dependent not only on the quality of the
      equipment used, training of the investigator, correct determination of the
      pancreatic field, but also on the experience and cooperation of the team
      performing the investigation.

PMID- 1365809
TI  - The effect of administering dexamethasone on the histochemical reactions in rats'
      liver.

PMID- 1365810
TI  - The course of typhoid fever in a woman treated in the Clinic of Infectious
      Diseases, Medical Academy in Lublin.

PMID- 1365811
TI  - Propositional reasoning by model.
AB  - This article describes a new theory of propositional reasoning, that is,
      deductions depending on if, or, and, and not. The theory proposes that reasoning
      is a semantic process based on mental models. It assumes that people are able to
      maintain models of only a limited number of alternative states of affairs, and
      they accordingly use models representing as much information as possible in an
      implicit way. They represent a disjunctive proposition, such as "There is a
      circle or there is a triangle," by imagining initially 2 alternative
      possibilities: one in which there is a circle and the other in which there is a
      triangle. This representation can, if necessary, be fleshed out to yield an
      explicit representation of an exclusive or an inclusive disjunction. The theory
      elucidates all the robust phenomena of propositional reasoning. It also makes
      several novel predictions, which were corroborated by the results of 4
      experiments.

PMID- 1365812
TI  - DNA cleavage by hydroxyl radicals generated in a vanadyl ion-hydrogen peroxide
      system.
AB  - Vanadyl ion (+4 oxidation state) has been shown to be an effective agent for
      chemoprotection of cancers in animals. For understanding the mechanism,
      distribution of vanadium was studied. More vanadium was found to accumulate in
      the nuclei of the liver of rats when it was given as vanadyl sulfate than when it
      was given as sodium vanadate (+5 oxidation state). The reactivity of vanadyl ion
      with DNA was investigated by the DNA cleavage technique and the reaction
      mechanism by ESR spectroscopy. Incubation of double-strand DNA with vanadyl ion
      and hydrogen peroxide resulted in marked concentration- and pH-dependent DNA
      cleavage. Studies by the ESR spin-trap method demonstrated that hydroxyl radicals
      are generated during the reactions of vanadyl ion with hydrogen peroxide. Thus
      the antineoplastic action of vanadyl ion is proposed to be due to DNA cleavage by
      hydroxyl radicals generated in the cells.

PMID- 1365813
TI  - Long-term mortality after primary prevention for cardiovascular disease.

PMID- 1365814
TI  - General practitioners and skin biopsy.

PMID- 1365815
TI  - Study of the conformational stability of 7S globulin from french beans
      (phaseolin) using high-sensitivity differential scanning microcalorimetry.
AB  - The change of the conformational stability and quaternary structure of the 7S
      globulin from french beans (phaseolin) has been investigated in the pH range 2.0
      11.0 using the high-sensitivity differential scanning microcalorimetry technique.
      It has been established that each polypeptide chain of phaseolin consists of two
      thermodynamically unequivalent cooperative domains. The number and type of the
      side-chain hydrogen bonds which participate in the stabilization of the folded
      structure of each domain have been determined. The more stable domain contains
      six side-chain hydrogen bonds: four of the carboxylate-tyrosyl type and two of
      the carboxylate-histidyl type. The less stable domain contains four side-chain
      hydrogen bonds: two of the carboxylate-tyrosyl type and two of the carboxylate
      histidyl type. All these side-chain hydrogen bonds appear to be localized within
      the hydrophobic interior of the domains. It has been found that the 3S form of
      phaseolin that is a product of the complete phaseolin dissociation at extreme pH
      values does not undergo any cooperative transition at heating. Consequently, this
      form probably has a conformation of 'molten globule' type.

PMID- 1365816
TI  - Selective inhibition of arthropod-borne and arenaviruses in vitro by 3'-fluoro-3'
      deoxyadenosine.
AB  - A novel nucleoside analog, 3'-fluoro-3'-deoxyadenosine (3'F3'dAdo), was evaluated
      for antiviral activity against several arthropod-borne and arenaviruses in Vero
      cell culture. The following 50% inhibitory concentrations (EC50) of virus plaque
      formation were obtained against the test viruses: Semliki Forest (10.3 microM)
      and Venezuelan equine encephalitis (5.3 microM) alphaviruses, lymphocytic
      choriomeningitis (7.7 microM) and Pichinde (greater than 32 microM) arenaviruses,
      Punta Toro (greater than 32 microM) and San Angelo (1.6 microM) bunyaviruses,
      banzi flavivirus (4.0 microM), and Colorado tick fever orbivirus (0.6 microM). By
      comparison, the broad-spectrum antiviral agent ribavirin was active against
      lymphocytic choriomeningitis (18 microM), Pichinde (24 microM), Punta Toro (114
      microM), and San Angelo (99 microM) viruses, but was less active against the
      other 4 viruses (greater than 200 microM). Vero cell proliferation and thymidine
      and uridine incorporation into replicating Vero cells were inhibited by 50% with
      3'F3'dAdo concentrations of 36, 45, and 32 microM, respectively. In virus yield
      reduction assays, increasing the multiplicity of infections of Semliki Forest and
      Venezuelan equine encephalitis viruses reduced the inhibitory activity of
      3'F3'dAdo. Using the same assay, 3'F3'dAdo was found to enhance Punta Toro virus
      replication up to 5-fold relative to the untreated control. By adding the
      nucleoside transport inhibitor nitrobenzylthioinosine (100 microM) to the culture
      medium, antiviral activity against the two alphaviruses was eliminated,
      indicating that 3'F3'dAdo uses the nucleoside transport system for cell entry.
      When actinomycin D (5 microM) was used to greatly suppress cellular RNA synthesis
      in Semliki Forest virus-infected and uninfected cells, 3'F3'dAdo preferentially
      inhibited viral RNA synthesis. The results of these studies indicate 3'F3'dAdo is
      a selective inhibitor of most of the viruses tested and should be a promising
      candidate for in vivo evaluations.

PMID- 1365817
TI  - [Contraception using a subcutaneous implant, Norplant].
AB  - The contraceptive device Norplant, not yet commercialized in Belgium, has been
      studied prospectively on 198 women, which were followed for up to 42 months per
      patient. All together, 2,643 months of use were surveyed. Norplant consists of 6
      silastic capsules, liberating levonorgestrel, a synthetic progestagen. The
      pregnancy protection lasts for 5 years. Insertion site is the inner part of the
      upper arm. The Pearl Index was 0.46% women-years (only one pregnancy occurred);
      the continuity rate was high (86% after 1 year and 60% after 2 years). The main
      side effects were menstrual disturbances and abnormal intermenstrual blood loss.
      No other important side effects have been found. There is no absolute contra
      indication to the use of Norplant.

PMID- 1365818
TI  - Free levonorgestrel index and its relationship with luteal activity during long
      term use of Norplant implants.
AB  - Levonorgestrel serum levels and sex hormone binding globulin (SHBG) were measured
      in 82 women during different years of use of Norplant implants. The ratio between
      levonorgestrel and SHBG was calculated as an indicator of the free biologically
      active fraction of levonorgestrel (free levonorgestrel index, FLI). These
      parameters were then correlated with the presence of luteal activity, as
      determined by progesterone levels above 9.6 nmol/L, in a sampling run of 10
      samples taken twice a week for five consecutive weeks. Levonorgestrel serum
      levels remained constant around 1.0 nmol/L during the five-year period. SHBG
      levels were below normal for the first 18 months of use, returning to normal
      levels during the last three years of use. The FLI in the first two years was
      significantly higher than that observed in the later years. The frequency of
      cycles with luteal activity was 12% during the first 2 years, increasing to 44%
      in the latter years, when FLI levels were lower. Our results suggest that the
      changes in SHBG and consequently in the free biologically active fraction of
      levonorgestrel may largely account for the differences in degree of ovarian
      suppression observed between the first two years of use of Norplant implants and
      the latter three, even in the absence of a significant variation in total
      levonorgestrel concentrations.

PMID- 1365819
TI  - The acceptability of Norplant in Egypt.
AB  - Currently, the pill and IUD account for 83% of contraceptive use in Egypt;
      Norplant will be an important complement to those methods of family planning. In
      Egypt where childbearing begins early, and closely spaced pregnancies are the
      norm, the long duration of Norplant's effectiveness and its relative ease of use
      should be appealing. The Egyptian Fertility Care Society (EFCS) initiated a study
      in 1988 on the acceptability of Norplant in Egypt to study the clientele of the
      EFCS clinical trial in the five university teaching hospitals. The clinical trial
      participants were women in their thirties who had an average of four children.
      Most had used a method of family planning before Norplant, and were anxious to
      maintain contraceptive protection as most wanted no more children. Satisfaction
      with Norplant among users was high. In the survey, 93% of the women expressed
      satisfaction with the method. More than half (67%) of the women said they would
      consider using Norplant again in the future, and another 22% were undecided.
      Eighty-seven percent of the women who had not discontinued were planning to
      continue with their current Norplant set for the full five years. Egyptian women
      like Norplant because of its long duration of effectiveness, the site of
      insertion, its ease of use, and its relative lack of perceived side-effects
      compared to the pill and IUD. In Egypt where a reliable, long-term, but not
      permanent method of contraception is badly needed, Norplant should become a
      popular method of family planning.

PMID- 1365820
TI  - Hypertension and kidney transplantation.
AB  - Hypertension in kidney transplant patients is a common complication that affects
      long-term patient and allograft survival. Although multifactorial in nature, at
      least two causes can be corrected by surgical or radiologic intervention-
      stenosis and native kidney-associated hypertension. Unfortunately, the current
      immunosuppressive agents have added to the problem of hypertension. Both
      prednisone and cyclosporine appear to aggravate posttransplant hypertension.
      Newer agents are on the horizon that may address this problem. Currently,
      physicians should consider the possibilities of correctable forms of
      hypertension. If none are indicated, medical therapy with renal vasodilating
      drugs such as calcium channel blockers or converting enzyme inhibitors or both
      along with diuretics are usually effective.

PMID- 1365821
TI  - Management of renal disease and hypertension in insulin-dependent diabetes, with
      an emphasis on early nephropathy.
AB  - In the follow-up of insulin-dependent diabetes mellitus patients with renal
      disease, a decline in glomerular filtration rate measured by an exact technique
      is the major primary end point in evaluating the progress of the disease.
      Abnormal albuminuria is considered an intermediate or secondary end point. All
      studies suggest that an increase in albuminuria indicates a decline or a risk of
      future decline in glomerular filtration rate. The main risk factor for
      progression appears to be the elevated blood pressure (which in itself may be a
      pathogenetic factor) that is associated with abnormal albumiuria from the
      microalbuminuric level. Abnormal albuminuria seems to always be associated with
      the risk of progression, and a reversal of abnormal albuminuria suggests a
      beneficial prognosis. Abnormal albuminuria is easily monitored by immunochemical
      procedures, including semiquantitative dipstick tests that may be important in
      renal screening procedures. Elevated blood pressure is important for the
      progression of abnormal albuminuria, but poor metabolic control seems to be the
      major initiating factor (although the mechanisms at a molecular biologic level
      are less clear). New studies confirm the strong predictive value of
      microalbuminuria for overt renal disease. At the same time, it is clear that
      microalbuminuria is associated with many cardiovascular abnormalities that
      cluster in some patients and is clearly associated with a poor prognosis. An
      intervention strategy is to achieve the best possible metabolic control without
      creating hypoglycemic problems or too difficult a lifestyle. Increasingly,
      studies underscore the value of early antihypertensive therapy, especially with
      angiotensin-converting enzyme inhibitors, in patients with microalbuminuria. This
      scenario of earlier and earlier antihypertensive treatment for microalbuminuric
      patients is evolving. Numerous studies indicate that microalbuminuria is
      stabilized or reversed by this treatment, and some new evidence suggests better
      preservation of glomerular filtration rate by this intervention program.
      Accumulating results also suggest considerable improvement in survival rate with
      this program in proteinuric insulin-dependent diabetes mellitus patients.

PMID- 1365822
TI  - Management of chronic renal failure.
AB  - There is growing evidence that treatment of patients with renal function
      impairment will undergo a major shift within the next few years. Along with more
      or less successful attempts to alleviate the signs and symptoms of reduced renal
      function, new insights into renal pathophysiology as well as new therapeutic
      modalities have given rise to the notion that we may be able to retard the
      naturally occurring decline in renal function in patients with diabetic and
      nondiabetic nephropathy.

PMID- 1365823
TI  - The molecular biology of mammalian glucose transporters.
AB  - Recent advances concerning the function and regulation of the facilitative and
      sodium-dependent glucose transport proteins are discussed. Physiologic roles have
      been proposed for GLUT3 and GLUT5 in the brain and intestine, respectively. Cell
      biologists are beginning to elucidate the subcellular trafficking pathways of
      GLUT4 in insulin-responsive cells. New members of the SGLT family, including a
      sodium-nucleoside cotransporter, have been identified.

PMID- 1365824
TI  - Management of glomerular diseases of primary and secondary origin.
AB  - Most recent information on the management of glomerular diseases is clustered in
      three areas. In nephrotic syndrome, interest has focused on the use of
      cyclosporine in steroid-resistant patients, treatment of progressive membranous
      nephropathy with alkylating agents, and symptomatic management of unresponsive
      cases with angiotensin-converting enzyme inhibitors. The most recent data on
      lupus nephritis establish the efficacy of intravenous cyclophosphamide in the
      long-term preservation of renal function and the lack of benefit of
      plasmapheresis in patients with severe disease. In rapidly progressive
      glomerulonephritis, the discovery of circulating antibodies to neutrophil
      cytoplasmic antigens has proved valuable in diagnosing certain forms of renal
      vasculitis. A rational approach to treating such patients is beginning to
      crystallize.

PMID- 1365825
TI  - Prevention and attenuation of acute renal failure.
AB  - Recent progress in our understanding of the pathogenetic processes involved in
      ischemic acute renal failure is considerable. Blockade of the production of
      endothelium-derived relaxing factor may markedly improve survival in patients
      with septic shock. Atrial natriuretic peptide and growth factors enhance renal
      recovery in animal models of acute renal failure, even when administered well
      after the ischemic insult. Aminoglycosides and radiocontrast agents are the most
      common causes of drug-induced acute renal failure. Once-daily administration of
      aminoglycosides is an effective treatment modality that may limit the occurrence
      of nephrotoxicity. Awareness of the patient's volume status has decreased the
      incidence of radiocontrast-induced acute renal failure. The new, expensive,
      nonionic, low-osmolar radiocontrast agents do not offer apparent benefits in
      patients with normal or slightly decreased renal function. However, use of such
      agents may decrease the incidence of radiocontrast-induced renal failure in
      diabetic patients with severe renal failure. The prognosis for patients with
      renal vasculitis has improved greatly in the past decade. The discovery of
      antibodies directed against antigenic targets in the cytoplasm of neutrophils has
      facilitated the diagnosis of renal vasculitides, has improved our knowledge of
      the pathogenesis of these diseases, and may guide rational treatment.

PMID- 1365826
TI  - Molecular cell biology and physiology of solute transport.

PMID- 1365827
TI  - Pharmacology and therapeutics.

PMID- 1365828
TI  - ATP-sensitive potassium channels in physiology, pathophysiology, and
      pharmacology.
AB  - Potassium-selective ion channels, whose activity is inhibited by micromolar to
      millimolar concentrations of ATP presented at the cytoplasmic ATP-sensitive K+
      (K+[ATP]) surface, have been found in a variety of cell types. These "K+(ATP)
      channels" have emerged as significant targets for physiologic as well as
      pharmacologic modulation of cell processes. In insulin-secreting beta cells of
      the pancreatic islet, closure of these channels on presentation of a metabolite
      secretogogue, such as glucose, or an oral hypoglycemic sulfonylurea, results in
      cell depolarization and triggers electrical activity. Ultimately, this results in
      Ca2+ entry and Ca(2+)-dependent exocytosis of insulin granules. In myocytes,
      opening of K+(ATP) channels during hypoxia or metabolite deprivation or with
      exposure to a new class of K+ channel opener drugs results in cell
      hyperpolarization and myocyte relaxation. This contributes to vasodilation. In
      renal tubule cells, K+(ATP) channels contribute to cell potassium balance during
      vectorial bulk solute transfer by the proximal tubule as well as net urinary
      potassium secretion by the distal nephron. Agents that modulate the activity of
      these K+(ATP) channels in epithelial cells may prove to be useful as K(+)-sparing
      diuretics. in epithelial cells may prove to be useful as K(+)-sparing diuretics.

PMID- 1365829
TI  - The molecular biology of chloride channels.
AB  - The molecular biology of chloride channels is a new field, having begun only 5
      years ago with the cloning, on the basis of partial amino acid sequence
      information, of complementary DNAs for subunits of the neuronal glycine and gamma
      aminobutyric acid-receptor channels. The sequences of these subunits that form
      heterooligomeric channels revealed a general similarity with the structural motif
      employed by the well-studied and previously cloned nicotinic acetylcholine
      receptor subunits. The principal distinguishing feature was the rings of
      positively charged residues within the loops separating the putative
      transmembrane helices of the new chloride selective channels. A great diversity
      of subunit types with specific functional and pharmacologic properties as well as
      localizations within the central nervous system have been identified and cloned.
      Chloride channels are known to play an important role in both secretion and
      reabsorption of salt and fluid across wet epithelia, and the cystic fibrosis
      transmembrane conductance regulator, cloned by genetic means, has been shown to
      be centrally involved in both of these processes. It is regulated by a complex
      mechanism involving both ATP binding and phosphorylation at multiple sites.
      Expression cloning techniques have yielded a voltage-gated family of channels
      with a large number of potential membrane spanning segments; one member is
      responsible for the resting potential of skeletal muscle. An entirely different
      low molecular weight-voltage-gated channel, possibly regulated by osmolarity
      changes, is the most recent chloride channel to be cloned. It almost certainly
      will not be the last.

PMID- 1365830
TI  - Osmolytes.
AB  - The cells of the renal medulla osmotically adapt to chronic alterations in
      extracellular tonicity by appropriate changes in the intracellular contents of
      organic osmoeffectors. The major organic osmolytes are glycerophosphorylcholine,
      betaine, myo-inositol, sorbitol, and, possibly, taurine. When the concentrations
      of poorly permeant external solutes are acutely reduced, cells that have been
      adapted to high tonicities rapidly release organic osmolytes via specific
      transmembrane transport pathways. In contrast, when medullary cells are depleted
      of organic osmolytes, osmolyte accumulation on acute elevation of external
      tonicity is slow and involves stimulation of uptake, intracellular de novo
      synthesis, or inhibition of intracellular degradation, and is preceded by
      increased intracellular electrolyte concentrations. The available evidence
      suggests that this rise in intracellular ionic strength plays an important role
      in the initiation of those processes responsible for full adaptation of renal
      medullary cells to high tonicities. Recently, complementary DNAs encoding a myo
      inositol and a betaine transporter have been isolated.

PMID- 1365831
TI  - Cellular and molecular mechanisms of renal development and tubulogenesis.
AB  - Recent advances in the basic mechanisms of developmental biology have started to
      shed new light on the mechanisms of nephrogenesis. The kidney is the only
      epithelial organ that starts as mesenchyme and converts to epithelium. It appears
      that the mesenchyme is composed of stem cells that are able to form glomeruli and
      proximal and distal tubules under the inductive influences of the ureteric bud.
      Epithelial cells cultured in a three-dimensional matrix could be induced to form
      tubules under the influence of a soluble factor from fibroblasts. This factor was
      identified as scatter factor or hepatocyte growth factor. Polycystic kidney
      disease appears to be a developmental renal disease in which a basolateral
      protein, the Na/K ATPase, is mistargeted to the apical and lateral membranes.

PMID- 1365832
TI  - Renal epithelial cell polarity.
AB  - Recent cell biologic studies of protein trafficking, sorting, and distribution in
      polarized renal epithelial cells have begun to provide important new insights
      into the mechanisms involved in generating and maintaining cell surface polarity.
      Advances in this field have been rapid in the last year, due in part to the
      development of new approaches to analyzing protein delivery and distribution in
      polarized renal cells grown in vitro. Sorting signals within apical and basal
      lateral membrane proteins have been described that may be involved in the
      segregation of proteins into different populations of transport vesicles in the
      trans-Golgi network; the nature of these signals has provided insight into the
      mechanisms involved. Elements of the cytoskeleton appear to be involved in the
      delivery of these transport vesicles to the appropriate membrane domain
      (microtubules) and in the retention of specific proteins in the correct membrane
      domain (membrane skeleton). Finally, detailed analysis of two prominent renal
      diseases, ischemia and polycystic kidney disease, indicates that abnormalities in
      the regulation of membrane protein distribution may be a contributing factor in
      generating the disease state.

PMID- 1365833
TI  - Defects in membrane transport of ions as possible pathogenic factors in
      hypertension.
AB  - Although abnormalities in cellular ion transport have been shown in a variety of
      cells of essential hypertensives, the mechanistic link between these
      abnormalities and elevated blood pressure is poorly understood. Reduced sodium
      potassium ATPase activity, with and without elevated levels of a circulating
      inhibitor of this transport system, has been reported by a number of studies. The
      recent characterization of the endogenous ouabain or its isomer will facilitate
      the testing of the hypothesis that salt-sensitive essential hypertension relates
      to higher levels of this factor. The erythrocyte sodium-lithium countertransport
      may serve as a marker for a subpopulation of essential hypertensives. However,
      this transport system has no physiologic counterpart and thus does not provide
      insight into mechanisms associated with altered cellular ionic homeostasis in
      essential hypertension. Increased activity of the sodium-hydrogen antiport in
      essential hypertension relates to an alkaline shift in the cytosolic pH set-point
      for activation of this transport system. This process may reflect increased
      cytosolic free calcium concentration with or without augmented protein kinase C
      activity.

PMID- 1365834
TI  - The phosphoinositide signaling system and hypertension.
AB  - The phosphoinositide signaling system is common to many vasoconstrictor agents
      and as such is influential in the regulation of blood pressure. Recently, there
      have been major advances in our understanding of these lipids and their
      metabolism. Characterization of the phospholipase C isozymes and protein kinase C
      isozymes involved in transmembrane signaling has progressed rapidly. The role of
      diacylglycerol kinase as a regulator of protein kinase C activity has been
      established, and phosphatidic acid has been recognized as a cellular messenger.
      Studies in the spontaneously hypertensive rat have shown abnormalities of
      phospholipase C that could result in enhanced activity and explain changes in
      sensitivity reported in rats with this disease. During agonist activation of
      inositol lipid hydrolysis, levels of inositol 1,4,5-trisphosphate and 1,2
      diacylglycerol are elevated in spontaneously hypertensive rats compared with
      Wistar-Kyoto control rats. These changes are observed early, prior to blood
      pressure stabilization, and may be downregulated once hypertension is
      established. In addition, there is evidence for reduced diacylglycerol kinase
      activity and enhanced protein kinase C activity in the spontaneously hypertensive
      rat. These data provide evidence for hyperresponsiveness of the phosphoinositide
      signaling system in the developmental stages of hypertension. However,
      confirmatory experiments in nongenetic animal models of hypertension and in human
      tissues are needed to establish that this is not just a phenotypic phenomenon of
      the spontaneously hypertensive rat.

PMID- 1365835
TI  - Nonpharmacologic treatment of hypertension.
AB  - A variety of lifestyle modifications will lower both the blood pressure and
      various other cardiovascular risk factors that are frequently present in patients
      with hypertension. Numerous recent studies document the overall efficacy of some
      (weight reduction, sodium restriction, physical activity, moderation of alcohol)
      and the relative lack of effect of others (stress management and calcium,
      magnesium, and fish oil supplements). In particular, the Trials of Hypertension
      Prevention, Phase I (a control trial funded by the National Heart, Lung, and
      Blood Institute) provides important new data on the ability of these various
      modalities to prevent the development of hypertension, an equally or even more
      important goal than the reduction of already-established disease.

PMID- 1365836
TI  - New classes of antihypertensive drugs and new findings with established agents.
AB  - Research on antihypertensive drugs not only provides new information on presently
      used agents but also leads to the introduction of exciting new compounds. Several
      important clinical trials involving currently available drugs have been published
      recently. Angiotensin-converting enzyme inhibitors improved survival in patients
      with milder degrees of congestive heart failure, which indicates that they have
      become the cornerstone of treatment for this condition. Angiotensin-converting
      enzyme inhibitors delayed or prevented the development of diabetic proteinuria (>
      200 micrograms/min) in a placebo-controlled randomized trial. Further, enalapril
      was more effective than metoprolol in reducing the rate of decline in renal
      function in patients with type I diabetes. Calcium channel blockers protected
      against acute renal failure in patients after renal transplantation in two
      separate studies. Calcium channel blockers were shown to promote natriuresis,
      with negative sodium balance the same as that associated with thiazide diuretics.
      The voltage-dependent calcium channel has been cloned, and the binding sites of
      the three classes of calcium channel blockers are now known. beta-Blockers and
      thiazide diuretics were the drug treatments in the Systolic Hypertension in the
      Elderly Program trial and in the Swedish Trial in Old Patients with Hypertension
      study (patients 65 to 85 years). In both investigations, stroke and
      cardiovascular events were significantly reduced by these conventional
      inexpensive agents. Clonidine was found to lower blood pressure primarily by its
      interaction with the imidazole receptor rather than the alpha 2 receptor.
      Elucidation of the imidazole receptor promises to shed light on physiologic
      mechanisms as well as lead to the introduction of new agents, such as
      moxonidine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1365837
TI  - Detection and serotyping of rotaviruses in stool specimens by using reverse
      transcription and polymerase chain reaction amplification.
AB  - Direct rotavirus serotyping (VP7, G type) in stool specimens was carried out by
      reverse transcription and polymerase chain reaction amplification (RT-PCR) and
      compared to serotyping by enzyme immunoassay with monoclonal antibodies (EIA
      MAb). The methods used for double-stranded (ds) RNA extraction, RT-PCR
      amplification, and the primers used were modified from previous reports [Gouvea
      et al.: Journal of Clinical Microbiology 29:519-523, 1990; Gentsch et al.:
      Journal of Clinical Microbiology, 1992]. For samples that were positive by both
      methods, the serotypes obtained were identical, however RT-PCR typing was found
      to be considerably more sensitive (70.4% samples serotyped) than EIA-MAb (35.6%
      of samples serotyped). The overall sensitivities for detection of rotavirus in
      stool samples by latex agglutination, enzyme immunoassay, electron microscopy,
      polyacrylamide gel electrophoresis, and RT-PCR were essentially the same. The
      results confirm that RT-PCR typing (genotyping) is extremely valuable for G
      typing of samples which cannot be typed by EIA-MAb. We also developed a PCR
      confirmation technique for serotypes 1, 2, and 4.

PMID- 1365838
TI  - Alzheimer skin fibroblasts show increased susceptibility to free radicals.
AB  - We have studied the response to toxic oxygen metabolites of fibroblasts derived
      from skin biopsies of 5 patients with familial (FAD) and 4 with sporadic (AD)
      Alzheimer's disease compared with those derived from 4 normal controls.
      Fibroblasts were damaged by the generation of oxygen metabolites during the
      enzymatic oxidation of acetaldehyde by 50 munits of xanthine-oxidase (Xo). To
      quantify cell damage we measured lactate dehydrogenase (LDH) activity in the
      culture medium and cell viability in fibroblast cultures. We found a significant
      increase in LDH activity in the FAD vs. controls and also in the AD vs. controls.

PMID- 1365839
TI  - Age-related excretion of six glycosidases in rat urine.
AB  - The activity of beta-N-acetylglucosaminidase (NAG), beta-galactosidase, alpha-L
      fucosidase, beta-glucuronidase, beta-glucosidase and alpha-mannosidase was
      determined in the urine of rats at progressive ages from newborn to old animals.
      The age-dependence of urinary creatinine, protein and pH values was also studied.
      Enzyme activity, related to urinary creatinine, was significantly higher in the
      newborn group than other ages. The excretion of NAG increased significantly in
      adult rats (3-6 months old) compared to young rats (1 month old). Most of the
      enzyme activities were diminished in old rats (25 months old). Increased
      proteinuria and creatinine excretion were observed in rats since 3 months of age.
      Age-related differences among enzyme activities therefore should be considered
      when these urinary glycosidases are to be studied in rats.

PMID- 1365840
TI  - Effects of aging on exocrine immune responses to Mycoplasma pulmonis.
AB  - Formalinized Mycoplasma pulmonis was used to immunize 3 different age groups of
      Fischer 344 rats. A specific antibody to this antigen was detected in both saliva
      and lung lavage fluids and differences were noted in the elicitation of secretory
      antibody between the different ages of the animals. Few statistical differences
      were noted between the three age groups for salivary IgG responses to M.
      pulmonis, regardless of the dosage given, even though all responses were greater
      than their respective control groups. The principal differences among the three
      age groups were noted in the kinetics of the response, that is, the amount of
      time that was necessary to produce a peak response. The younger group of animals
      took less time to produce a peak response than the older two groups, even though
      the magnitude of the response was lower. Salivary IgA responses to M. pulmonis
      appeared predominantly as a primary response, particularly in the senescent
      animals. Secondary salivary IgA responses were not significantly greater than
      their respective primary responses, suggesting that secretory IgA did not display
      classic anamnestic responses that were observed with salivary IgG. As with IgG
      responses, the senescent animals took longer to produce a peak salivary IgA
      response when compared to the other age groups. Lung lavage IgG responses,
      normalized to total protein, were greatest in the youngest group of animals and
      appeared to diminish as the age of the animal increased. In contrast, lung lavage
      IgA responses to M. pulmonis were of a greater magnitude in the senescent
      animals. These studies suggest that senescent animals are capable of eliciting a
      humoral immune response in mucosal secretions to Mycoplasma pulmonis. However,
      differences noted with regard to disease severity and mortality to respiratory
      mycoplasmosis in senescent animals may result from intrinsic defects in the
      quality of the humoral response or as a consequence of deficient cellular
      responses to this pathogen.

PMID- 1365841
TI  - Effect of aging on macrophage adherence to extracellular matrix proteins.
AB  - Fibronectin, type I, type IV and type V collagens were compared for their
      abilities to promote mouse peritoneal resident macrophage adherence and the
      effect of aging on macrophage adhesion to these matrix proteins was examined.
      Adherence of macrophages to fibronectin was remarkable and more than 5-fold
      compared to type I, type IV or type V collagens. Adherence of macrophages to
      fibronectin and type I collagen increased during aging. However, no age-related
      changes were observed in macrophage adherence to type IV and type V collagens.
      The percent of inhibition of macrophage adherence to fibronectin by arginine
      glycine-aspartic acid-serine (RGDS) peptide (58.1 +/- 2.7%) was significantly (P
      < 0.01) higher than that in cells from young mice (23.1 +/- 5.7%). These data
      suggest that macrophage attach preferentially to fibronectin and that the ability
      of macrophage to attach to fibronectin increases during aging. The age-related
      increase in macrophage attachment to fibronectin is related to the concentration
      of cell surface receptors of macrophage which recognize RGDS sequence within
      fibronectin during aging. Adherence of macrophage to fibronectin implies
      retention of macrophages in subendothelial space. Age-related increase in
      macrophage ability to attach to fibronectin may be related to atherogenesis
      during aging.

PMID- 1365842
TI  - Heavy metals and lipofuscinogenesis. A study on myocardial cells cultured under
      varying oxidative stress.
AB  - The aim of this study was to examine the influence on lipofuscinogenesis of a
      number of transition and non-transition heavy metals in cultured post-mitotic
      cells (neonatal rat myocytes) at varying oxidative stress. The effects of Al, Cd,
      Cr, Cu, Hg, Pb and Zn, added to the medium as chlorides, were examined after 14
      days in culture under 5, 20 and 40% ambient oxygen. Lipofuscin was quantified by
      microspectrofluorometry of individual cells. The addition of Al (40 microM), Cd
      (40 nM), Hg (30 microM) and Pb (40 microM) to the culture growth medium markedly
      increased the amount of intracellular lipofuscin, whereas Cr (40 microM), Cu (40
      microM) and Zn (40 microM) had the opposite effect. Transmission electron
      microscopic examination of the myocytes showed greatly increased numbers of
      autophagic vacuoles in cells exposed to those heavy metals that increased
      lipofuscin formation. This effect was most pronounced when cells were grown at
      high (40%) oxygen tension. Possible explanations for the metal augmented pigment
      formation may be (i) inhibition of lysosomal enzymes, (ii) catalytic interference
      with peroxidative reactions, or (iii) general toxicity with unspecifically
      increased autophagocytosis. The decreased pigment accumulation after the addition
      of Zn, Cr and Cu may, at least partly, be related to the replacement of iron,
      which has catalytic activity in Fenton reactions.

PMID- 1365843
TI  - The effects of age on the pharmacokinetics and biotransformation of theophylline
      in vivo and in vitro in the Mongolian gerbil (Meriones unguiculatus).
AB  - The effect of post maturational aging on the in vivo disposition of theophylline
      was examined in the Mongolian gerbils (Meriones unguiculatus) aged 30-39 (old),
      12-18 (middle-aged) and 3 (young) months following a 20 mg/kg i.p. dose.
      Biotransformation of theophylline was also examined in liver microsomes from non
      induced and 3-methylcholanthrene induced gerbils. Analysis of theophylline plasma
      kinetics showed decreased clearance, increased half-life and increased volume of
      distribution in old vs. young animals. Clearance to the 1,3-dimethyluric acid
      metabolite was similar for all age groups, while clearance to the 1-methyluric
      acid metabolite was significantly lower in the middle-aged group compared to that
      of young and old gerbils. Urinary recovery of 1-methylurate was increased in old
      vs. young and middle-aged animals while recovery of theophylline was decreased. 3
      Methylcholanthrene induction resulted in decreased recovery of theophylline and
      increased recovery of 1,3-dimethylurate and 1-methylurate in young and middle
      aged gerbils compared to non-induced controls. Decreased microsomal protein
      content was observed in old vs. young and middle-aged gerbils and an age-related
      decrease in cytochrome P-450 content (nmol P-450/g liver) was also observed. The
      rate of dimethylurate formation was decreased 37% in microsomes from old vs.
      young and middle-aged gerbils. 3-Methylcholanthrene administration resulted in a
      2- and 1.5-fold increase in the rate of 1,3-dimethylurate formation in young and
      middle-aged gerbils, respectively. The results of these experiments indicate that
      the Mongolian gerbil may be useful for the study of the biochemical mechanisms
      underlying age-related changes in the biotransformation and kinetics of
      theophylline.

PMID- 1365844
TI  - Plasmic membranes of hepatocytes and adrenocorticocytes in rats of different
      ages: effect of testosterone.
AB  - Experiments on adult (6-8-month-old and 26-28-month-old) Wistar rats revealed the
      hyperpolarization of plasmic membranes and activation of Na,K-ATPase of
      adrenocorticocytes in animals of both age groups and of hepatocytes of adult
      rats. No effect of testosterone was observed on the level of membrane potential
      and the activity of Na,K-ATPase of hepatocytes of old rats. The effect of
      testosterone was prevented by inhibitors of protein biosynthesis (actinomycin D
      and cycloheximide) and a specific inhibitor of Na,K-ATPase (ouabain), but not by
      K(+)-channel blocker 2-aminopyridine. Testosterone was assumed to synthesize the
      specific factor, capable of activating Na,K-ATPase of plasmic membranes. The
      cytosole of hepatocytes and the blood serum of adult testosterone-treated rats
      activated the Na,K-ATPase of isolated plasmic membranes of hepatocytes of adult
      and old intact rats. During aging there was a decrease in the capacity of cells
      to synthesize the specific factor, which activated Na,K-ATPase of plasmic
      membranes.

PMID- 1365845
TI  - Age-related morphological and morphometrical changes in parvalbumin- and
      calbindin-immunoreactive neurons in the rat hippocampal formation.
AB  - Parvalbumin (PV)- and calbindin (CaBP)-immunostaining in the hippocampal
      formation of 3-, 11- and 28-month-old Wistar rats was studied using monoclonal
      antibodies. A quantitative analysis of the densities, cross-sectional areas,
      length and number of processes of PV-immunoreactive neurons in the hippocampal
      dentata and CA1 areas of the three age groups was employed. Marked age-related
      changes in the morphological appearance and in the quantitative parameters
      characterizing the PV-immunoreactive neurons in both hippocampal regions were
      observed. The intensity of CaBP-immunostaining of the hippocampal principle cells
      and interneurons remained the same but the immunoreactive fibers were
      structurally altered in aging.

PMID- 1365846
TI  - Homeostasis between lipid peroxidation and antioxidant enzyme activities in
      healthy human aging.
AB  - In healthy people the plasma malondialdehyde increases with age, however there is
      a simultaneous rise in the activities of glucose-6-phosphate dehydrogenase and 6
      phosphogluconate dehydrogenase in red blood cells, although both enzymes show a
      biphasic behaviour, that is, reaching the lowest values at 40-50 years of age to
      rise remarkably later on. No significant changes were found in the case of
      glutathione peroxidase but the age-dependent behaviour is similar to the other
      enzymes mentioned above. The activity of glutathione reductase shows a clear
      increase depending on age, up to middle age, with or without flavin adenine
      dinucleotide. We conclude that the increase in the activities of the anti-oxidant
      enzymes of the red blood cells during aging, could be interpreted as a positive
      feedback mechanism in response to rising lipid peroxidation. Consequently, from
      the point of view of the parameters used the homeostasis between the production
      of free radicals and anti-oxidant systems seems to be maintained in the common,
      normal aging pattern.

PMID- 1365847
TI  - Successful islet transplantation in the thymus of spontaneously diabetic BB rats.

PMID- 1365848
TI  - Prevalence of hepatitis C in multitransfused Tunisian patients.

PMID- 1365849
TI  - Psychiatrists in the new NHS.

PMID- 1365850
TI  - Parameters of care for oral and maxillofacial surgery. A guide for practice,
      monitoring and evaluation (AAOMS Parameters of Care-92). American Association of
      Oral and Maxillofacial Surgeons.

PMID- 1365851
TI  - Pretreatment with aldosterone or corticosterone blocks the memory-enhancing
      effects of nimodipine, captopril, CGP 37,849, and strychnine in mice.
AB  - Oral pretreatment with aldosterone or corticosterone blocked the memory-enhancing
      effects of the calcium antagonist nimodipine, the ACE inhibitor captopril, the
      NMDA blocker CGP 37,849, and the glycine antagonist strychnine in a passive
      avoidance test in mice. The memory-disturbing effects of phenobarbitone,
      diazepam, CGP 37,849 and scopolamine were not influenced by the hormonal
      pretreatment. These findings could indicate the involvement of a steroid
      sensitive mechanism in drug-induced improvement of memory. In the light of
      clinical observations showing elevated cortisol levels in Alzheimer patients, the
      results might also explain why only a limited number of these patients respond to
      therapy with memory enhancers.

PMID- 1365852
TI  - Control of turning behavior under apomorphine by sensory input from the face.
AB  - It has been shown that peripheral manipulation of sensory input by removal of
      vibrissae on one side of the rat's face induces turning behavior which is
      directed towards the contralateral vibrissae-intact side, under the influence of
      the dopamine receptor agonist apomorphine. In the present experiment, we examined
      whether rats under apomorphine turn towards the side with more sensory input, or
      simply away from the manipulated side. Thus, an experimental manipulation was
      designed to increase sensory input. Sensory stimulation was applied by attaching
      a clip into the fur on one side of the face. Rats injected with apomorphine in
      doses of 0.5-5.0 mg/kg (but not with 0.05 mg/kg or vehicle) exhibited turning
      behavior towards the side of the clip. This sensory stimulation was also found to
      influence spontaneous behavioral asymmetries. These results show that an
      imbalance in sensory input is sufficient to produce turning under apomorphine.

PMID- 1365853
TI  - Effects of anxiolytic and antidepressant drugs on long-lasting behavioural
      deficits resulting from one short stress experience in male rats.
AB  - Exposure of male Wistar rats to one single session of ten inescapable footshocks
      induces changes in the behavioural responses to environmental stimuli as measured
      in the "noise test" 14 days later. Shocked (S) rats showed decreased locomotion
      and rearing during the first 3 min of exposure to a novel environment compared to
      control (C) rats. When the 85 dB background noise was switched off a marked
      immobility response emerged in S rats, concomitant with a further decrease in
      locomotion and rearing. In response to noise off, C rats showed hardly any
      immobility and a much smaller reduction in locomotion and rearing compared to S
      rats. These long-lasting changes in behaviour were not reversed by acute
      treatment with the antidepressants fluvoxamine (3.0-30.0 mg/kg) and
      desmethylimipramine (DMI, 2.5-10.0 mg/kg) injected IP 30 min before the noise
      test on day 14 following the shock session. Chronic treatment (day 1 to day 14)
      with fluvoxamine or DMI did not reverse the behavioural deficits induced by shock
      exposure. Diazepam (0.6-5.0 mg/kg) administered acutely only reversed the effects
      of shock on locomotion during the first 3 min of the noise test. Chronic
      treatment with diazepam normalized the shock-induced decrease in locomotion and
      attenuated the rearing decrease during the first 3 min of the test, and partially
      restored shock-induced changes in behavioural response to switching off the
      noise. The most potent drug in this study was the 5-HT1A receptor agonist
      flesinoxan (0.3-3.0 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1365854
TI  - Differential antagonism of the effects of dopamine D1-receptor agonists on
      feeding behavior in the rat.
AB  - A series of experiments was conducted to examine the effects of dopamine D1
      receptor agonists on food intake in rats. In the first experiment, the D1 agonist
      SKF 38393 (3.0-30.0 mg/kg) dose-dependently suppressed feeding during a 40 min
      food-access period, both in food-deprived rats and in non-deprived rats fed a
      highly palatable diet. Non-deprived rats were more sensitive to these effects of
      SKF 38393. Using the limited-access, food-deprivation procedure, a comparison was
      made between the anorectic effects of three D1 agonists with differing intrinsic
      efficacies and receptor selectivities. Rank order of potencies for reducing food
      intake was SKF 82958 > SKF 77434 > SKF 38393 (ED50 values: 0.7, 3.6 and 15.7
      mg/kg, respectively). Dose-related, surmountable antagonism by the D1 antagonist
      SCH 23390 (0.01 and 0.03 mg/kg) was only obtained with SKF 82958 (0.1-10.0
      mg/kg). In contrast to the other compounds, the effects of SKF 38393 were not
      appreciably altered by the D1 antagonist. The effects of SKF 82958 were also
      antagonized by the D2 receptor antagonist spiperone (0.05 and 0.1 mg/kg),
      although not in a dose-dependent manner. The present results support a role for
      D1 receptors in central feeding mechanisms. They also suggest that the effects of
      SKF 38393 on feeding may not be mediated exclusively by the D1 receptor and,
      further, that SKF 38393 may not serve well in behavioral studies as a
      prototypical D1 agonist. The results also demonstrate the need for comparisons
      among several compounds in studies of D1 mediated behavioral effects.

PMID- 1365855
TI  - Increased [3H] raclopride binding sites in postmortem brains from schizophrenic
      violent suicide victims.
AB  - The specific binding of the D2-dopamine receptor antagonist radioligand [3H]
      raclopride was quantitated in the postmortem caudate and frontal cortex from
      schizophrenic suicide victims and control subjects. In schizophrenic suicides the
      density of binding sites (Bmax) was higher (40%, P < 0.05) in the caudate,
      whereas it did not change in the cortex as compared to those in controls. The
      apparent dissociation constants (KD) were also found increased both in caudate
      (24%) and cortex (75%) from schizophrenics, but these apparent decreases in
      receptor affinity did not reach statistical significance. The mean Bmax value in
      drug-free schizophrenic suicides (n = 3) did not differ from the Bmax value in
      neuroleptic drug-treated schizophrenics (n = 7) but it was found increased in
      respect to control subjects (n = 9). No differences in [3H] raclopride binding
      were observed between non-schizophrenic suicide victims (n = 4) and matched
      controls (n = 4), suggesting that the modifications of D2-dopamine receptors in
      schizophrenia are not related to suicide.

PMID- 1365856
TI  - Differential effects of serotonergic and catecholaminergic drugs on ingestive
      behavior.
AB  - The serotonergic agonists fenfluramine and fluoxetine and the catecholaminergic
      agonists amphetamine and phenylpropanolamine are well known to cause a reduction
      in intake in rats. In the studies reported here we investigated the effects of
      these drugs on the microstructure of licking behavior of the rat ingesting 0.4 M
      sucrose. The purpose was to examine the similarities in the behavioral effects
      within and between these two classes of anorectic agents. The serotonergic
      agonists fenfluramine and fluoxetine caused a reduction in intake primarily by
      reducing the size of bursts and clusters of licking within the test meal without
      affecting the duration of the meal, suggesting a reduction in the palatability of
      the test solution. The catecholamine agonists amphetamine and phenylpropanolamine
      reduced intake primarily by reducing the number of bursts and clusters without
      affecting their size, suggesting a fractionation in the organization of the
      normal pattern of ingestion. The differences between the two serotonin and the
      two catecholamine agonists on the microstructure of the licking behavior suggest
      a different effect of the two neurotransmitters on the motor system that controls
      ingestive behavior. The similarities between the two different agonists within
      each class suggests a common neurotransmitter mechanism responsible for these two
      different effects on the behavior of the animals.

PMID- 1365857
TI  - The metabolic fate of infused L-tryptophan in men: possible clinical implications
      of the accumulation of circulating tryptophan and tryptophan metabolites.
AB  - L-Tryptophan (Trp) was widely used as a natural tool for the support of serotonin
      mediated brain functions and as a challenge probe for the assessment of serotonin
      mediated neuroendocrine responses. The metabolic fate of the administered Trp and
      the kinetics of the accumulation of Trp metabolites in the circulation, however,
      have never thoroughly been investigated. This study describes the time- and dose
      dependent alterations in the plasma levels of various Trp metabolites and large
      neutral amino acids after the infusion of Trp to healthy young men (1, 3 and 5 g;
      placebo-controlled, double-blind, cross-over study during day- and night-time).
      The major Trp metabolites (kynurenine, indole acetic acid and indole lactic acid)
      in plasma increased dose-dependently but rather slowly after Trp administration
      to reach their maximal plasma levels (up to 10-fold after the 5 g dose) at about
      3 h p.i., and remained at an elevated level (about 5-fold) for up to 8 h. N
      acetyl-Trp and 5-hydroxy-Trp rose rapidly and massively after Trp infusions, at
      the 5 g dose more than 200- and 20-fold, respectively, and declined rapidly to
      about 5-fold baseline levels within 2 h. Whole blood serotonin levels were almost
      unaffected by the Trp infusions. A rather slow increase of 5-hydroxyindole acetic
      acid was seen, reaching maximum values (3-fold at the 5 g dose) at about 2 h
      after the infusion of Trp. Additionally, a dose-dependent rise of circulating
      melatonin was observed after L-Trp infusions. The administration of L-Trp caused
      a depletion of the concentrations of the other large neutral amino acids and a
      dose dependent decrease of the ratio between plasma tyrosine and the sum of the
      plasma concentrations of the other large neutral amino acids. Apparently, none of
      the existing pathways of peripheral Trp metabolism is saturated by its substrate,
      Trp in men. At least some of the central effects reported after L-Trp
      administration may be mediated by the Trp-stimulated formation of neuroactive
      metabolites or by the decreased availability of tyrosine for catecholamine
      synthesis.

PMID- 1365858
TI  - Reversal of stress-induced anhedonia by the atypical antidepressants, fluoxetine
      and maprotiline.
AB  - Chronic exposure to mild unpredictable stress has previously been found to
      depress the consumption of palatable sweet solutions. In the present study this
      effect was reversed by chronic (9 weeks) treatment with the atypical
      antidepressants, fluoxetine and maprotiline (5 mg/kg/day); the non-antidepressant
      chlordiazepoxide was ineffective. Stressed animals were also subsensitive to food
      reward in the place conditioning procedure; however, fluoxetine and maprotiline
      treated animals showed normal place preference conditioning. Acute pretreatment
      with raclopride (100 micrograms/kg) selectively reversed the recovery of sucrose
      drinking in antidepressant-treated stressed animals. These results extend
      previous reports of the efficacy of tricyclic antidepressants in this paradigm,
      and support the hypothesis of a dopaminergic mechanism of antidepressant action.

PMID- 1365859
TI  - Scopolamine impairs delayed matching in an olfactory task in rats.
AB  - The action of the cerebral cholinergic system seems to be important for
      remembering events over short time intervals. We decided to test this hypothesis
      in the rat by developing an original model of short term memory based on the
      olfactory sensory modality which is a major determinant in the animal behaviour.
      The principle of the experiment was a "delayed match-to-sample" test performed in
      a classical T maze divided into two compartments. In the first compartment, rats
      received an odorant stimulation, then, in the second, they had to discriminate
      between the two arms odorized differently. To receive a food reinforcement, the
      animals had to enter the arm signaled by the odor presented in the first part of
      the maze. The test was performed with (Short-term memory condition) or without
      (Immediate memory condition) a variable delay between the first odor sampling and
      the discrimination task. Both tests were performed with control and scopolamine
      treated animals (0.5, 0.125 and 0.0625 mg/kg IP). An injection of scopolamine
      (0.5 mg/kg) impaired performances, even when no retention of the odor was
      required. However, lower doses (0.125, 0.0625 mg/kg) selectively altered
      performances in the short term memory condition. These results suggest that
      intact muscarinic transmission is required for an olfactory cue to be used over a
      short time after its presentation.

PMID- 1365860
TI  - Evidence for involvement of 5-HT1C and 5-HT2 receptors in the food intake
      suppressant effects of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI).
AB  - Administration of various doses of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      (DOI) to rats produced dose-related decreases in 1-h food intake in the food
      deprived paradigm. Pretreatment with spiperone (5-HT1A/5-HT2/D2 antagonist),
      propranolol or CGP361A (beta-adrenoceptor antagonists that also have binding
      affinities for 5-HT1A and 5-HT1B sites) and MDL-72222 (5-HT3 antagonist) did not
      attenuate DOI-induced suppression of food intake. In contrast, pretreatment with
      metergoline (5-HT1/5-HT2 antagonist) completely blocked whereas mesulergine,
      mianserin and ritanserin (5-HT1C/5-HT2 antagonists) partially blocked DOI's
      effect on food intake. On the other hand, pretreatment with MDL-72222 but not
      with m-chlorophenylpiperazine (m-CPP) significantly potentiated DOI-induced
      suppression of food intake. Furthermore, the food intake suppressant effects of
      various doses of DOI were found to be similar in the Fawn-Hooded (FH) rat strain
      as compared to the Wistar rat strain. These findings suggest that DOI-induced
      suppression of food intake is mediated by stimulation of both 5-HT1C and 5-HT2
      receptors.

PMID- 1365862
TI  - Dose-dependent effect of GM1 ganglioside during development on inhibitory
      avoidance behaviour in mice: influence of the period of administration.
AB  - Groups of C57BL/6 mice were injected intraperitoneally with GM1
      monosialoganglioside at different ages during development and subsequently tested
      for the retention of an inhibitory avoidance task 24 h after training. Results
      show improvements in inhibitory avoidance retention according to the age of the
      animals, the doses of GM1 used and the length of treatment. The effective doses
      ranged from 20 mg/kg for all age groups after 7 days treatment to 280 mg/kg for 6
      and 7-week old animals after pre-trial treatment. Six- and 7-week-old mice are
      more sensitive to GM1 treatment than 5-week-old animals and, with decreasing
      lengths of treatment, increasing doses of GM1 are needed to improve the
      performance of the animals. These findings show that short treatment durations
      can be effective in improving inhibitory avoidance retention as long as the doses
      of GM1 administered are increased and that animals are more sensitive to the
      treatment when they are 6 or 7 weeks of age than when they are 5 weeks old.

PMID- 1365861
TI  - Nicotine elimination and tolerance in non-dependent cigarette smokers.
AB  - Although most smokers are nicotine-dependent, recent studies suggest that some
      very light smokers ("chippers", who smoke fewer than five cigarettes per day) may
      smoke for decades without developing dependence. It was considered that slowed
      nicotine elimination and/or reduced nicotine tolerance might underlie chippers'
      ability to maintain smoking at such low levels. To evaluate this hypothesis, we
      studied the elimination kinetics and pharmacodynamics of nicotine in chippers and
      matched regular smokers. Plasma nicotine levels and cardiovascular responses were
      observed for several hours after subjects were administered uniform doses of
      tobacco smoke. Chippers did show less chronic nicotine tolerance, but only on
      some response measures. Their rates of nicotine elimination equaled those of
      regular smokers. This finding, when coupled with other data about chippers'
      smoking patterns and nicotine absorption, establish that chippers cannot maintain
      substantial plasma nicotine levels between cigarettes, and thus suggest that
      attempts to maintain minimal trough levels of nicotine do not underlie chippers'
      smoking.

PMID- 1365863
TI  - Effects of the 5-HT3 antagonist ondansetron on benzodiazepine-induced operant
      behavioural dependence in rats.
AB  - This study was designed to assess whether rats made tolerant to the suppressant
      action on Fixed Ratio operant responding of the benzodiazepine (BZ)
      chlordiazepoxide (CDP) would show behavioural disruption on drug withdrawal--so
      called operant behavioural dependence. In addition, the study examined the
      effects of the 5-HT3 antagonist ondansetron on such operant behavioural
      dependence. During 42 consecutive days of CDP treatment, at doses escalated from
      10 to 30 mg/kg/day, marked tolerance developed to the rate-suppressant action of
      CDP. On subsequent days, during spontaneous withdrawal, response rates declined
      significantly by around 30% in animals treated with saline, although some
      recovery of responding was seen over successive days of withdrawal. Similar
      reductions in responding followed by recovery were seen in rats treated with the
      5-HT3 antagonist ondansetron (0.01-0.1 mg/kg, b.i.d.). These findings demonstrate
      for the first time that it is possible to use operant procedures to detect
      spontaneous BZ withdrawal. They also suggest, in agreement with recent studies
      from this laboratory (Leathley and Goudie 1992), that 5-HT3 antagonists may have
      relatively limited utility in treating some signs of BZ dependence.

PMID- 1365864
TI  - Hyperthermia induced by m-trifluoromethylphenylpiperazine (TFMPP) or m
      chlorophenylpiperazine (m-CPP) in heat-adapted rats.
AB  - TFMPP and m-CPP, non-selective 5-HT agonists, administered in doses of 1-20 mg/kg
      evoked hyperthermia in rats at a high ambient temperature (28 degrees C). The
      hyperthermic effect of TFMPP (10 mg/kg) or m-CPP (10 mg/kg) was dose-dependently
      antagonized by the 5-HT1c and 5-HT2 receptor antagonists mesulergine (0.5-4
      mg/kg), ketanserin (0.6-2.5 mg/kg) and ritanserin (0.5-2 mg/kg) and by the non
      selective 5-HT antagonist metergoline (0.5-1 mg/kg), or was attenuated by the 5
      HT1A, 5-HT2 and dopamine receptor antagonist spiperone (3 mg/kg, but not 0.3 or 1
      mg/kg). On the other hand, the 5-HT1A, 5-HT1B and beta adrenoceptor antagonists
      pindolol (2 mg/kg) and cyanopindolol (2 mg/kg), the 5-HT1A receptor
      agonist/antagonist ipsapirone (10 and 35 mg/kg) and haloperidol (0.25 and 0.5
      mg/kg) showed a tendency towards enhancing the TFMPP- or m-CPP-induced
      hyperthermia. The 5-HT1A and alpha 1-adrenoceptor antagonist NAN-190 (1-4 mg/kg),
      the 5-HT3 antagonists tropisetron (0.01-1 mg/kg) and zacopride (0.5 and 1 mg/kg),
      the beta-blockers betaxolol (8 mg/kg) and ICI 118, 551 (8 mg/kg), which have no
      affinity for 5-HT receptors and prazosin (1 mg/kg), did not affect the
      hyperthermic effect of TFMPP or m-CPP. The hyperthermias studied were not
      modified, in animals with 5-HT lesion produced by p-chloroamphetamine (PCA)
      either. All the drugs used as putative receptor antagonists, as well as PCA, did
      not change or decreased (ipsapirone) the body temperature in heat-adapted
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1365865
TI  - Amperozide and clozapine but not haloperidol or raclopride increase the secretion
      of oxytocin in rats.
AB  - The aim of the present study was to investigate whether amperozide, an
      antipsychotic drug which possesses anti-aggressive and anxiolytic-like
      properties, stimulates the secretion of oxytocin and if so, by which receptor
      mechanism. For this purpose, female or male Sprague Dawley rats were given
      amperozide (0.5, 2.5 and 5.0 mg/kg IP), ritanserin (5.0 mg/kg), raclopride (2.0
      mg/kg) and prazosin (1.0 mg/kg) and were subsequently decapitated for collection
      of blood (30 and 120 min) after injection. Oxytocin levels were measured with
      radioimmunoassay. Amperozide 2.5 and 5 mg/kg increased plasma levels of oxytocin
      significantly (P < 0.05 and < 0.001). The effect appeared maximal about 30 min
      after injection of the drug and oxytocin levels were almost back to basal within
      120 min. Similar effects were obtained in female and male rats as well as in
      animals that were freely fed or food deprived for 24 h. CSF levels of oxytocin
      were also increased. Ritanserin, a 5-HT2-receptor antagonist but not the D2
      receptor antagonist raclopride or the alpha 1-adrenoceptor antagonist prazosin
      stimulated oxytocin release. In addition, clozapine, a neuroleptic with potent
      HT2-antagonistic properties, was a potent releaser of oxytocin, whereas
      haloperidol was without effect. A possible role for oxytocin in the behavioural
      effects of amperozide and clozapine remains to be explored.

PMID- 1365866
TI  - D1/D2 dopamine and N-methyl-D-aspartate (NMDA) receptor participation in
      experimental catalepsy in rats.
AB  - Mixed D1/D2 dopamine (DA) antagonists, perphenazine (5 mg/kg) and haloperidol (2
      mg/kg) induced catalepsy in rats. SCH 23390 (1 mg/kg), a D1 DA antagonist, also
      produced catalepsy. Co-administration of perphenazine (0.5 mg/kg) and SCH 23390
      (0.1 mg/kg), at low doses, produced a marked increase in cataleptic response. B
      HT 920, a D2 agonist, reversed the cataleptogenic effects of perphenazine,
      haloperidol and SCH 23390. SKF 38893 (5 mg/kg) reduced the cataleptogenic effect
      of SCH 23390 but failed to reverse haloperidol- or perphenazine-induced
      catalepsy. SKF 38393 (10 mg/kg), however, protected the animals against
      perphenazine- induced catalepsy. Combined administration of B-HT 920 (0.1 mg/kg)
      and SKF 38393 (5 mg/kg) enhanced the protective effect of B-HT 920 in SCH 23390
      treated animals but not in animals treated with haloperidol or perphenazine. MK
      801 (0.025-0.5 mg/kg), a non-competitive N-methyl-D-aspartate (NMDA) receptor
      antagonist, reduced the cataleptogenic effects of perphenazine, haloperidol as
      well as SCH 23390. The anticataleptic action of MK-801 was enhanced by
      scopolamine (0.1 mg/kg) but not by bromocriptine (1 mg/kg) or clonidine (0.05
      mg/kg) in perphenazine-treated rats. Unlike B-HT 920 (0.1 mg/kg), SKF 38393 (5
      mg/kg) potentiated the anticataleptic effect of MK-801 (0.01 mg/kg) against SCH
      23390-induced catalepsy. The above data suggests D1/D2 interdependence in
      catalepsy and a modulatory role of D1 and D2 DA receptor stimulation on the
      anticataleptic effect of MK-801.

PMID- 1365867
TI  - Performance of baboons under a repeated acquisition procedure during chronic oral
      exposure to atenolol and propranolol.
AB  - Repeated acquisition behavioral performances of normotensive and renovascular
      hypertensive baboons were tested before, during, and following chronic oral
      dosing with the beta-adrenergic antagonists atenolol HCl (2.6 mg/kg/day PO), and
      d,l propranolol HCl (6.8 mg/kg twice daily PO) in separate studies. Each study
      administered active drug for 21 consecutive days preceded and followed by 14-day
      baseline and recovery periods, respectively. Animals pressed five keys in
      sequence for food reinforcement during daily experimental sessions which
      consisted of alternating acquisition (new sequence learning) and performance
      (previously learned) task components. Atenolol increased response latencies
      during acquisition in comparison to performance components, and during early
      portions of sessions. Propranolol also increased response latencies during
      acquisition components in early periods of sessions, but fewer dependent measures
      were affected, and the magnitude of increases in response latencies was smaller
      (12% +/- 5 SEM) as compared with atenolol (47% +/- 13). Test doses of
      phencyclidine HCl (PCP) increased latencies to the same degree as atenolol. PCP
      markedly reduced accuracy, while atenolol or propranolol did not. Blood pressures
      remained stable under atenolol, and decreased by approximately 10-15 mmHg under
      propranolol. No differences between renovascular hypertensive and normotensive
      baboons were found as a function of drug conditions. Drug effects were not
      dependent on plasma propranolol concentration.

PMID- 1365868
TI  - Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance
      and mental effort.
AB  - This study evaluates the effects of vitamin B-6 supplementation (20 mg pyridoxine
      HCL daily for 3 months) on mood and performance in 38 self-supporting healthy
      men, aged between 70-79 years. Effects were compared with 38 controls who
      received placebo and were matched for age, plasma pyridoxal-5'-phosphate (PLP)
      concentration and intelligence score. Before and after drug intervention vitamin
      B-6 status was determined, and mood and performance were measured by means of a
      computerized testing system. In addition, the phasic pupil response was measured
      in order to assess mental effort. Positive effects of vitamin B-6 supplementation
      were only found with respect to memory, especially concerning long-term memory.
      In view of the finding that mental performance improvement and delta PLP values
      were most strongly correlated within an intermediate range of delta PLP, it is
      suggested that cognitive effects are primarily associated with a certain range of
      vitamin B-6 status increment. The general conclusion is that vitamin B-6
      supplementation improves storage of information modestly but significantly.

PMID- 1365869
TI  - Concentration of ondansetron in cerebrospinal fluid following oral dosing in
      volunteers.
AB  - This study measured the concentrations of ondansetron in plasma and cerebrospinal
      fluid (CSF) in six volunteers after oral dosing to steady state. Ondansetron
      concentrations ranged from 39.5-147 ng ml-1 in plasma and from 2.6-15.4 ng ml-1
      in CSF. There was good correlation between plasma and CSF concentrations (r =
      0.89, p = 0.017). CSF concentrations were less than 15% of plasma concentrations
      in all cases, indicating that the rate of penetration of the blood brain barrier
      by ondansetron is low.

PMID- 1365870
TI  - A patient with osteomalacia as single presenting symptom of gluten-sensitive
      enteropathy.
AB  - A 59-year-old male patient presented with invalidating osteomalacia of 2.5 years'
      duration. The osteomalacia was caused by severe malabsorption due to gluten
      sensitive enteropathy (GSE). There were no other signs or symptoms of GSE in this
      patient. Clinical presentation with monosymptomatic osteomalacia is very unusual.
      It seems that patients with GSE who undergo little exposure to the sun are at
      particular risk of developing overt osteomalacia. Unrecognized GSE should always
      be considered in the differential diagnosis of osteomalacia.

PMID- 1365871
TI  - Unexplained biliary tract dilatation in lung cancer patients.
AB  - Three patients, two men and one woman, diagnosed as having adenocarcinoma of the
      lung were found to have changes in cholestatic biochemical values, and CT scan of
      the abdomen demonstrated dilation of the biliary tree. Upon further evaluation
      using ERCP marked dilation of the biliary tree was confirmed. There was no
      anatomic obstruction to bile flow, no neoplastic involvement of the liver or bile
      ducts and no evidence of any infiltrative process or disease to explain the
      dilation. A paraneoplastic syndrome is proposed as the etiology of the biliary
      tract abnormality. Along with other more common causes, this newly described
      paraneoplastic syndrome should be considered in the differential diagnosis of
      lung cancer in patients presenting with cholestasis and biliary tract dilation.

PMID- 1365872
TI  - Initiation of chromosome replication in eukaryotic cells.

PMID- 1365873
TI  - How do cells control the timing of DNA replication and mitosis?

PMID- 1365874
TI  - The control of timing and spatial organization during Caulobacter cell
      differentiation.

PMID- 1365875
TI  - Cellular and viral transcriptional activators.

PMID- 1365876
TI  - Mutational analyses of lymphocyte differentiation.
AB  - The site-specific recombination mechanism responsible for the assembly of antigen
      receptor variable region genes is only employed in lymphocyte development. Gene
      targeted and other types of mutational analyses have implicated at least seven
      distinct gene products, some lymphoid-specific and others more generally
      expressed, as involved in aspects of this process. Mutation of the lymphocyte
      specific activities required for VDJ recombination or mutation of the target gene
      segments of this process have created B and/or T cell-deficient mouse models that
      have provided new insights into the regulation of the VDJ recombination reaction
      and into how the successful achievement of this reaction at various loci helps
      lead lymphocytes through their early developmental program A second type of B
      lymphocyte-specific recombination process is involved in heavy-chain class
      switching; gene-targeted mutation approaches also have provided new insights into
      the cis-acting elements that target of this reaction to particular CH genes.

PMID- 1365877
TI  - Mammalian origins of replication.
AB  - It has been almost twenty-five years since Huberman and Riggs first showed that
      there are multiple bidirectional origins of replication scattered at
      approximately 100 kb intervals along mammalian chromosomal fibers. Since that
      time, every conceivable physical property unique to replicating DNA has been
      taken advantage of to determine whether origins of replication are defined
      sequence elements, as they are in microorganisms. The most thoroughly studied
      mammalian locus to date is the dihydrofolate reductase domain of Chinese hamster
      cells, which will be used as a model to discuss the various methods of
      investigation. While several laboratories agree on the rough location of the
      'initiation locus' in this large chromosomal domain, different experimental
      approaches paint different pictures of the mechanism by which initiation occurs.
      However, a variety of new techniques and synchronizing agents promises to clarify
      the picture for this particular locus, and to provide the means for identifying
      and isolating other origins of replication for comparison.

PMID- 1365878
TI  - On the nature of origins of DNA replication in eukaryotes.
AB  - Chromosomal origins of DNA replication in higher eukaryotes differ significantly
      from those of E. coli (oriC) and the tumor virus, SV40 (ori sequence). Initiation
      events appear to occur throughout broad zones rather than at specific origin
      sequences. Analysis of four chromosomal origin regions reveals that they share
      common modular sequence elements. These include DNA unwinding elements,
      pyrimidine tracts that may serve as strong DNA polymerase-primase start sites,
      scaffold associated regions, transcriptional regulatory sequences, and, possibly,
      initiator protein binding sites and inherently destabilized regions. Based on the
      novel organization of chromosomal origin regions, we propose a model for
      initiation of DNA replication in higher eukaryotes. Unwinding of duplex DNA
      during initiation may be uncoupled, both temporally and spatially, from DNA
      synthesis, resulting in transient single-stranded intermediates that function in
      lieu of conventional replication forks during chromosomal DNA replication. DNA
      synthesis begins subsequently at multiple sites within the unwound regions rather
      than at specific origin sequences.

PMID- 1365879
TI  - Recombinant neuromuscular synapses.
AB  - The developing neuromuscular junction has provided an important paradigm for
      studying synapse formation. An outstanding feature of neuromuscular
      differentiation is the aggregation of acetylcholine receptors (AChRs) at high
      density in the postsynaptic membrane. While AChR aggregation is generally
      believed to be induced by the nerve, the mechanisms underlying aggregation remain
      to be clarified. A 43-kD protein (43k) normally associated with the cytoplasmic
      aspect of AChR clusters has long been suspected of immobilizing AChRs by linking
      them to the cytoskeleton. In recent studies, the AChR clustering activity of 43k
      has, at last, been demonstrated by expressing recombinant AChR and 43k in non
      muscle cells. Mutagenesis of 43k has revealed distinct domains within the primary
      structure which may be responsible for plasma membrane targeting and AChR
      binding. Other lines of study have provided clues as to how nerve-derived
      (extracellular) AChR-cluster inducing factors such as agrin might activate 43k
      driven postsynaptic membrane specialization.

PMID- 1365880
TI  - Mesoderm induction and axis determination in Xenopus laevis.
AB  - In Xenopus, as in all amphibians and possibly in vertebrate embryos in general,
      mesoderm formation and the establishment of the dorsoventral axis depend on
      inductive cell interactions. Molecules involved in mesoderm induction include FGF
      which acts predominantly as a ventrolateral inducer, the TGF-beta homolog activin
      which can induce all types of mesoderm, and members of the Wnt family which have
      powerful dorsalizing effects. Early effects of inducer action include the
      activation of regulatory genes. Among such genes, particular interest is focused
      on three genes encoding putative transcription factors that are expressed
      specifically in the Spemann organizer region of the gastrula. Expression of one
      of these genes, goosecoid, has been shown to be sufficient to elicit the
      formation of a dorsal axis including head and notochord in the embryo.

PMID- 1365881
TI  - What have tissue culture studies told us about the development of
      oligodendrocytes?
AB  - One major success of studying neural cell development in tissue culture has been
      the discovery of the O-2A cell. This bipotential cell generates oligodendrocytes
      or, under certain conditions, a type of astrocyte. This essay considers the
      evidence that the characteristic properties demonstrated by the O-2A cells in
      vitro are an accurate reflection of oligodendrocyte development in vivo.

PMID- 1365883
TI  - Genes controlling specific cell fates in C. elegans embryos.

PMID- 1365882
TI  - AMP-activated protein kinase--an archetypal protein kinase cascade?
AB  - Mammalian AMP-activated protein kinase is the central component of a protein
      kinase cascade which inactivates three key enzymes involved in the synthesis or
      release of free fatty acids and cholesterol inside the cell. The kinase cascade
      is activated by elevation of AMP, and perhaps also by fatty acid and cholesterol
      metabolites. The system may fulfil a protective function, preventing damage
      caused by depletion of ATP or excessive intracellular release of free lipids, a
      type of stress response. Recent evidence suggests that it may have been in
      existence for at least a billion years, since a very similar protein kinase
      cascade is present in higher plants. This system therefore represents an early
      eukaryotic protein kinase cascade, which is unique in that it is regulated by
      intracellular metabolites rather than extracellular signals or cell cycle events.

PMID- 1365884
TI  - Evolution of mitochondrial genomes and the genetic code.
AB  - Mitochondrial genomes are clearly marked by a strong tendency towards reductive
      evolution. This tendency has been facilitated by the transfer of most of the
      essential genes for mitochondrial propogation and function to the nuclear genome.
      The most extreme examples of genomic simplification are seen in animal
      mitochondria, where there also are the greatest tendencies to codon reassignment.
      The reassignment of codons to amino acids different from those designated in the
      so called universal code is seen in part as an expression of the reduction of the
      number of genes used by these genomes to code for tRNA species. The driving force
      for the reductive evolution of mitochondrial genomes is identified with two
      population genetic effects which may also be operating on populations of
      parasites.

PMID- 1365885
TI  - Alzheimer's disease untangled.
AB  - The last year has seen major advances in the study of Alzheimer's disease (AD).
      Four mutations involving amino acid substitutions in exons 16 and 17 of the
      amyloid precursor protein (APP) gene, have been identified which co-segregate
      with the disease in some families multiply affected by early onset Alzheimer's
      disease. These mutations are strongly suggestive of a causative role for the
      amyloid precursor protein in Alzheimer's disease. Despite their rarity, these
      mutations are important because they represent the first known cause of
      Alzheimer's disease. Processing of APP must be central to the pathogenesis of the
      disease although the precise effects of these amino acid substitutions are not
      understood. Work is now being undertaken to characterise the processing pathways
      of APP and to identify other causes of AD. The development of models of AD using
      the APP mutations offers the possibility of identifying drug targets and
      developing more effective treatments than are presently available.

PMID- 1365886
TI  - The genetic control of tissue polarity in Drosophila.
AB  - The cuticular surface of Drosophila is decorated by parallel arrays of polarized
      structures such as hairs and sensory bristles; for example, on the wing each cell
      produces a distally pointing hair. These patterns are termed 'tissue polarity'.
      Several genes are known whose activity is essential for the development of normal
      tissue polarity. Mutations in these genes alter the orientation of the hair or
      bristle with respect to neighboring cells and the body as a whole. The phenotypes
      of mutations in these genes allows them to be placed in three phenotypic groups.
      Based on their behavior in genetic mosaics, it has proved possible to determine
      that individual genes are required either for the generation of an intercellular
      polarity signal and/or the transduction of that signal to the cytoskeleton.

PMID- 1365887
TI  - Phylogenetic analysis of the cadherin superfamily.
AB  - Cadherins are a multigene family of proteins which mediate homophilic calcium
      dependent cell adhesion and are thought to play an important role in
      morphogenesis by mediating specific intercellular adhesion. Different lines of
      experimental evidence have recently indicated that the site responsible for
      mediating adhesive interactions is localized to the first extracellular domain of
      cadherin. Based upon an analysis of the sequence of this domain, I show that
      cadherins can be classified into three groups with distinct structural features.
      Furthermore, using this sequence information a phylogenetic tree relating the
      known cadherins was assembled. This is the first such tree to be published for
      the cadherins. One cadherin subtype, neural cadherin (N-cadherin), shows very
      little sequence divergence between species, whereas all other cadherin subtypes
      show more substantial divergence, suggesting that selective pressure upon this
      domain may be greater for N-cadherin than for other cadherins. Phylogenetic
      analysis also suggests that the gene duplications which established the main
      branches leading to the different cadherin subtypes occurred very early in their
      history. These duplications set the stage for the diversified superfamily we now
      observe.

PMID- 1365888
TI  - The molecular and cell biology of anion transport by bacteria.
AB  - This article summarizes the study of anion exchange mechanisms in bacteria. Along
      with defining at least two different families of anion exchange, an examination
      of such carrier-mediated antiport reactions has led to techniques that
      considerably broaden the scope of biochemical methods for examining membrane
      proteins. Such advances have been exploited to show that anion exchange itself
      forms the mechanistic base of an entirely new kind of proton pump, one which may
      shed light on a variety of bacterial events, including methanogenesis. Perhaps
      most important, the study of exchange provided the final link in a chain of
      evidence pointing to a structural 'rhythm' that seems to characterize membrane
      carriers. These three issues--a biochemical tool, a new proton pump, and a common
      structural rhythm--are briefly examined in the context of their origins in the
      analysis of bacterial anion exchange.

PMID- 1365889
TI  - Mitochondrial DNA and genetic disease.
AB  - Since the human mitochondrial genome was characterised and sequenced in 1981, it
      has been viewed as the likely site of genetic diseases showing a maternal
      inheritance pattern and associated with defects of the respiratory chain, such as
      the mitochondrial myopathies (MMs). The properties that make it a candidate for
      the source of such conditions are that it encodes polypeptides involved in
      electron transport and that it is maternally inherited. However, several of the
      mtDNA diseases only fulfill one or other of these criteria: the first group of
      mtDNA diseases showed only sporadic deletions, and the first point mutation in
      Leber's Hereditary Optic Neuropathy (LHON) is not associated with a clear
      biochemical defect. Furthermore, it is now clear that both autosomal dominant and
      probably recessive nuclear genes can cause abnormalities of mtDNA. Each of these
      major groups will be considered in turn.

PMID- 1365890
TI  - Differentiation and proliferation in mouse embryonal carcinoma cells.
AB  - How cell commitment and differentiation are controlled in the early stages of
      embryogenesis is a problem that has long fascinated developmental biologists.
      Retinoic acid-induced differentiation of embryonal carcinoma cells in culture
      provides a model in which these questions can be explored. Recent work has
      yielded exciting insights into the central series of molecular changes which
      drives the commitment of these cells to formation of a new phenotype. Interacting
      with the key molecules in this central pathway is a variety of transcription
      factors, many of which show changes in availability and/or activity during
      differentiation. In various combinations, these modulate the activities of genes
      involved in both cell proliferation and in the production of extracellular matrix
      and other proteins characteristics of differentiated cells.

PMID- 1365891
TI  - Rho, rac and the actin cytoskeleton.

PMID- 1365892
TI  - The sex-peptide.
AB  - Injection of a peptide of 36 amino acids into virgin Drosophila females changes
      their reproductive properties drastically: males are rejected and egg laying is
      increased. The neuronal and physiological properties of the virgin state are
      replaced by a new pattern of behavior and stimulation of egg production and
      deposition. Under natural conditions, the peptide is synthesized by the male and
      transferred into the female during copulation. The sex-peptide, therefore, can be
      considered as a pheromone. In this review, I shall limit my discussion to
      Drosophila melanogaster.

PMID- 1365894
TI  - Barbara McClintock, 1902-1992.

PMID- 1365893
TI  - My favorite cytological subject: chromosomes.

PMID- 1365895
TI  - The hemopoietic regulators--an embarrassment of riches.
AB  - A large, and growing, group of glycoprotein regulators is now recognized to
      control the proliferation, maturation and functional activity of the eight major
      families of blood cells. Each hemopoietic regulator is the product of multiple
      cell types and there is a puzzling redundancy of regulators able to stimulate
      each subfamily of hemopoietic cells. Each regulator is polyfunctional but it
      remains unclear how a single type of activated receptor is able to initiate the
      diverse cellular responses induced.

PMID- 1365896
TI  - DNA triple-helix formation: an approach to artificial gene repressors?
AB  - Certain sequences of double-helical DNA can be recognized and tightly bound by
      oligonucleotides. The effects of such triple-helical structures on DNA binding
      proteins have been studied. Stabilities of DNA triple-helices at or near
      physiological conditions are sufficient to inhibit DNA binding proteins directed
      to overlapping sites. Such proteins include restriction endonucleases,
      methylases, transcription factors, and RNA polymerases. These and other results
      suggest that oligonucleotide-directed triple-helix formation could provide the
      basis for designing artificial gene repressors. The general question of whether
      biological systems employ RNA molecules for recognition and regulation of double
      helical DNA is discussed.

PMID- 1365897
TI  - Sex-chromosome pairing and activity during mammalian meiosis.
AB  - Mammalian sex chromosomes exhibit marked sexual dimorphism in behavior during
      gametogenesis. During oogenesis, the X chromosomes pair and participate in
      unrestricted recombination; both are transcriptionally active. However, during
      spermatogenesis the X and Y chromosomes experience spatial restriction of pairing
      and recombination, are transcriptionally inactive, and form a chromatin domain
      that is markedly different from that of the autosomes. Thus the male germ cell
      has to contend with the potential loss of X-encoded gene products, and it appears
      that coping strategies have evolved. Genetic control of sex-chromosome
      inactivation during spermatogenesis does not involve pairing or the presence of
      the Y chromosome or an intact X chromosome, and may therefore be under exogenous
      control by the gonad. Sex-chromosome reactivation during oogenesis and
      inactivation during spermatogenesis probably reflect specific meiotic events such
      as recombination. Understanding these phenomena may help explain other sex
      related differences in genetic recombination.

PMID- 1365898
TI  - DNA synthesis control in yeast: an evolutionarily conserved mechanism for
      regulating DNA synthesis genes?
AB  - After yeast cells commit to the cell cycle in a process called START, genes
      required for DNA synthesis are expressed in late G1. Periodicity is mediated by a
      hexameric sequence, known as a MCB element, present in all DNA synthesis gene
      promoters. A complex that specifically binds MCBs has been identified. One
      polypeptide in the MCB complex is Swi6, a transcription factor that together with
      Swi4 also binds G1 cyclin promoters and participates in a positive feedback loop
      at START. The finding that Swi6 is directly involved in both START and DNA
      synthesis gene control suggest a model in which Swi6, activated through its
      participation in START, serves as the central transcription factor in
      coordinating late G1 gene expression. The mechanism may be conserved in all
      eukaryotic cells.

PMID- 1365899
TI  - Mouse albino-deletions: from genetics to genes in development.
AB  - Six essential genes located near the mouse albino locus have been identified as
      required during specific periods of development. Amongst these six, each is
      required either during the preimplantation stages of development, at specific
      times during gastrulation, within 12 hrs after birth or during juvenile
      development. These genes were identified as a result of extensive genetic
      complementation analysis using embryos homozygous for the albino deletions.
      Although, in principal, the associated developmental abnormalities could result
      from loss of multiple genes, the deletion phenotype in one case is identical to
      that induced by chemical mutagenesis. These results indicate that the
      abnormalities observed in deletion homozygotes may result from single gene loss.
      The deletions have proven useful not only as genetic tools to localize the
      position of the genes, but also as molecular entry points to the regions
      containing these genes. The current methodology being used to isolate candidate
      genes from the albino region is also reviewed here.

PMID- 1365901
TI  - Imprintor or Imprinted?

PMID- 1365900
TI  - Control of steroid receptor function and cytoplasmic-nuclear transport by heat
      shock proteins.
AB  - As targeted proteins that move within the cell, the steroid receptors have become
      very useful probes for understanding the linked phenomena of protein folding and
      transport. From the study of steroid receptor-associated proteins it has become
      clear over the past two years that these receptors are bound to a multiprotein
      complex containing at least two heat shock proteins, hsp90 and hsp56. Attachment
      of receptors to this complex in a cell-free system appears to require the protein
      unfolding/folding activity of a third heat shock protein, hsp70. Like the
      oncogenic tyrosine kinase pp60src, steroid receptors bind to this complex of
      chaperone proteins at the time of their translation. Binding of the receptor to
      the hsp90 component of the system occurs through the hormone binding domain and
      is under strict hormonal control. The hormone binding domain of the receptor acts
      as a transferable regulatory unit that confers both tight hormonal control and
      hsp90 binding onto chimaeric proteins. The model of folding and transport being
      developed for steroid receptors leads to some general suggestions regarding the
      folding and transport of targeted proteins in the cell.

PMID- 1365902
TI  - The microtubule-organizing center.

PMID- 1365903
TI  - Molecular movements in oocyte patterning and pole cell differentiation.
AB  - Central to the differentiation and patterning of the Drosophila oocyte is the
      asymmetric intracellular localization of numerous mRNA and protein molecules
      involved in developmental signalling. Recent advances have identified some of the
      molecules mediating oocyte differentiation, specification of the anterior pole of
      the embryo, and determination of the embryonic germ line. This work is considered
      in the context of the classical model of the germ plasm as a cytoplasmic
      determinant for germ cell formation.

PMID- 1365904
TI  - How do germ cells choose their sex? Drosophila as a paradigm.
AB  - Sex determination in the germ line may either rely on cell-autonomous genetic
      information, or it may be imposed during development by inductive somatic
      signals. In Drosophila, both mechanisms contribute to ensure that germ cells are
      oogenic when differentiating in females and spermatogenic when differentiating in
      males. Some of the genes that are involved in germ line sex determination have
      been identified. In other species, including vertebrates, inductive signals are
      commonly used to determine the sex of germ cells.

PMID- 1365905
TI  - E. coli hemolysin interactions with prokaryotic and eukaryotic cell membranes.
AB  - The hemolysin toxin (HlyA) is secreted across both the cytoplasmic and outer
      membranes of pathogenic Escherichia coli and forms membrane pores in cells of the
      host immune system, causing cell dysfunction and death. The processes underlying
      the interaction of HlyA with the bacterial and mammalian cell membranes are
      remarkable. Secretion of HlyA occurs without a periplasmic intermediate and is
      directed by an uncleaved C-terminal targetting signal and the HlyB and HlyD
      translocator proteins, the former being a member of a transporter superfamily
      central to import and export of a wide range of substrates by prokaryotic and
      eukaryotic cells. The separate process by which HlyA is targetted to mammalian
      cell membranes is dependent upon fatty acylation of a non-toxic precursor,
      proHlyA. This is achieved by a novel mechanism directed by the activator protein
      HlyC, which binds to an internal proHlyA recognition sequence and provides
      specificity for the transfer of fatty acid from cellular acyl carrier protein.

PMID- 1365906
TI  - Role of the interleukin 5 receptor system in hematopoiesis: molecular basis for
      overlapping function of cytokines.
AB  - Interleukin 5 (IL-5) is a kind of peptide hormone released from T lymphocytes of
      mammals infected with microorganisms or parasites. It is an acidic glycoprotein
      with a molecular mass of 40 to 50 kDa that consists of a homodimer of
      polypeptides. It controls hematopoiesis so that it increases natural immunity. In
      the mouse, IL-5 acts on committed B cells to induce differentiation into Ig
      producing cells and on common progenitors for CD5+ pre-B cells and CD5+
      macrophages to support their survival. The antibodies secreted by CD5+ B cells
      seem to be responsible for the primary protection against the infection with
      microorganisms or parasites. It also supports the growth and/or differentiation
      of eosinophil precursor and mature eosinophils, which can be effective for the
      removal of parasites in combination with the antibodies against them. Murine IL-5
      receptor (IL-5R) consists of two different polypeptide chains; alpha chain and
      beta chain. The IL-5R alpha chain is 60 kDa protein that binds IL-5 with low
      affinity. The IL-5R beta chain is a 130 kDa protein which does not bind IL-5 by
      itself but is necessary to form the high affinity IL-5R. The beta chain was
      identified by using one of the anti-IL-5R mAb and anti-IL-3R mAb as the IL-3R
      homologue. This beta chain is also used as the beta chain of GM-CSF receptor.
      This fact suggests that there is a common signaling mechanism among these
      cytokines and efficient cooperation among them. At the same time, these findings
      may explain the overlapping role of these cytokines in the development of
      granulocytes.

PMID- 1365907
TI  - Membrane protein insertion into the endoplasmic reticulum--another channel
      tunnel?
AB  - The synthesis of biological membranes requires the insertion of proteins into a
      lipid bilayer. The rough endoplasmic reticulum of eukaryotic cells is a principal
      site of membrane biogenesis. The insertion of proteins into the membrane of the
      endoplasmic reticulum is mediated by a resident proteinaceous machinery. Over the
      last five years several different experimental approaches have provided
      information about the components of the machinery and how it may function.

PMID- 1365908
TI  - Is calpain activity regulated by membranes and autolysis or by calcium and
      calpastatin?
AB  - Although the Ca(2+)-dependent proteinase (calpain) system has been found in every
      vertebrate cell that has been examined for its presence and has been detected in
      Drosophila and parasites, the physiological function(s) of this system remains
      unclear. Calpain activity has been associated with cleavages that alter
      regulation of various enzyme activities, with remodeling or disassembly of the
      cell cytoskeleton, and with cleavages of hormone receptors. The mechanism
      regulating activity of the calpain system in vivo also is unknown. It has been
      proposed that binding of the calpains to phospholipid in a cell membrane lowers
      the Ca2+ concentration, [Ca2+], required for the calpains to autolyze, and that
      autolysis converts an inactive proenzyme into an active protease. Recent studies,
      however, show that the calpains bind to specific proteins and not to
      phospholipids, and that binding to cell membranes does not affect the [Ca2+]
      required for autolysis. It seems likely that calpain activity is regulated by
      binding of Ca2+ to specific sites on the calpain molecule, with binding to each
      site eliciting a response (proteolytic activity, calpastatin binding, etc.)
      specific for that site. Regulation must also involve an, as yet, undiscovered
      mechanism that increases the affinity of the Ca(2+)-binding sites for Ca2+.

PMID- 1365910
TI  - A protein complex present at origins of DNA replication in yeast cells.

PMID- 1365909
TI  - p53 loss of function: implications for the processes of immortalization and
      tumorigenesis.
AB  - The complex process of cell immortalization and transformation is likely to
      involve the inactivation of growth regulatory genes. Mutations (deletions,
      missense mutations) in the p53 gene are the most frequently observed genetic
      alteration in human tumors, making p53 a candidate for a cellular protein
      involved in the control of cell growth. Two recent studies have examined the role
      of p53 in immortalization and tumorigenesis. In the first study, p53 expression
      was examined in both mortal and immortal chick embryo fibroblasts. All mortal
      clones expressed p53 but the loss of wild-type p53 expression was observed in
      every immortal cell line examined. In the second study, a line of mice carrying
      two null p53 alleles has been created and characterized. Although these mice
      develop normally, they show a predisposition to develop a variety of neoplasms at
      an early age (< 6 months). Although it is unclear whether p53 regulates the same,
      different, or overlapping pathways in the two experimental systems, these data
      demonstrate that p53 function is critical for the maintenance of normal growth
      control and support the current classification of p53 as a growth suppressive or
      tumor suppressor gene.

PMID- 1365911
TI  - Genes, genes and more genes in the human major histocompatibility complex.
AB  - The human major histocompatibility complex (MHC), on the short arm of chromosome
      6, represents one of the most extensively characterised regions of the human
      genome. This approximately 4 Mb segment of DNA contains genes encoding the
      polymorphic MHC class I and class II molecules which are involved in antigen
      presentation during an immune response. Recently the whole of the MHC has been
      cloned in cosmids and/or yeast artificial chromosomes (YACs) and large portions
      have been characterised for the presence of novel genes. Many unrelated genes,
      both housekeeping and tissue specific, have been identified and the gene density
      in some regions is now approaching one gene every few kilobases. Some of the
      novel genes encode proteins involved in the intracellular processing and
      transport of antigens that are presented by MHC class I molecules. Others,
      however, have no obvious role in the immune response. The MHC is located in the
      chromosome band 6p21.3 which is a Giemsa (G)-light band. The detection of such a
      large number of functional genes (at least 70) in this region is compatible with
      the idea that both housekeeping and tissue-specific genes are localised
      predominantly in G-light bands.

PMID- 1365912
TI  - All animals develop from a blastula: consequences of an undervalued definition
      for thinking on development.
AB  - An early embryo becomes a blastula at the moment that its constituent cells
      become organised into a simple epithelium. Epithelial folding and
      compartmentation are essential elements of animal development. All the different
      cell types--epithelial and other ones--of which a differentiated organism
      consists differ in their plasmamembrane-cytoskeletal complex but they are assumed
      to have an identical genome. The hypothesis is put forward that, perhaps, the
      basic mechanism underlying differentiation can be defined as the generation of
      cells which have an identical genome but which differ in their plasmamembrane
      cytoskeletal complex and which, because of these differences, can engage in
      differential protein synthesis-physiology.

PMID- 1365913
TI  - HNF1, a homeoprotein member of the hepatic transcription regulatory network.
AB  - Numerous liver specific genes are transcriptionally activated by the binding to
      their promoter or enhancer of Hepatic Nuclear Factor 1 (HNF1). HNF1 contains a
      variant homeo-domain and binds to DNA as either a homodimer or a heterodimer with
      the vHNF1 protein. Surprisingly, HNF1 is not restricted to hepatocytes but is
      expressed in epithelial cells of several endoderm derived organs and in mesoderm
      derived kidney tubules. Hence, HNF1 alone can not account for the differentiated
      state of the hepatic cells. In fact, several other liver-enriched transcription
      factors have been cloned. The hepatic phenotype could result from the
      combinatorial expression of these regulators. Possible involvement of these trans
      acting factors in liver organogenesis and hepatic differentiation is discussed.

PMID- 1365914
TI  - The mechanism of receptor-mediated endocytosis: more questions than answers.
AB  - Receptor-mediated endocytosis occurs via clathrin-coated pits and is therefore
      coupled to the dynamic cycle of assembly and disassembly of the coat
      constituents. These coat proteins comprise part, but certainly not all, of the
      machinery involved in the recognition of membrane receptors and their selective
      packaging into transport vesicles for internalization. Despite considerable
      knowledge about the biochemistry of coated vesicles and purified coat proteins,
      little is known about the mechanisms of coated pit assembly, receptor-sorting and
      coated vesicle formation. Cell-free assays which faithfully reconstitute these
      events provide powerful new tools with which to elucidate the overall mechanism
      of receptor-mediated endocytosis.

PMID- 1365915
TI  - The interaction of transcription factors with nucleosomal DNA.
AB  - Nucleosome positioning is proposed to have an essential role in facilitating the
      regulated transcription of eukaryotic genes. Some transcription factors can bind
      to DNA when it is appropriately wrapped around the histone core, others cannot
      bind due to the severe deformation of DNA structure. The staged assembly of
      nucleosomes and positioning of histone-DNA contacts away from promoter elements
      can facilitate the access of transcription factors to DNA. Positioned nucleosomes
      can also facilitate transcription through providing the appropriate scaffolding
      to bring regulatory factors bound at dispersed sites into juxtaposition.

PMID- 1365916
TI  - Position effect variegation and chromatin proteins.
AB  - Variegated phenotypes often result from chromosomal rearrangements that place
      euchromatic genes next to heterochromatin. In such rearrangements, the condensed
      structure of heterochromatin can spread into euchromatic regions, which then
      assume the morphology of heterochromatin and become transcriptionally inactive.
      In position-effect variegation (PEV) therefore, gene inactivation results from a
      change in chromatin structure. PEV has been intensively investigated in the
      fruitfly Drosophila, where the phenomenon allows a genetic dissection of
      chromatin components. Consequently, many genes have been identified which, when
      mutated, act as dominant modifiers (suppressors or enhancers) of PEV. Data
      available already demonstrate that genetic, molecular and developmental analysis
      of these genes provides an avenue to the identification of regulatory and
      structural chromatin components, and hence to fundamental aspects of chromosome
      structure and function.

PMID- 1365917
TI  - The biology of hepatocyte growth factor/scatter factor.
AB  - Hepatocyte growth factor, a potent mitogen for epithelial and other cell types,
      and scatter factor, a stimulant of epithelial cell motility are identical. In
      addition to these mitogenic and motogenic functions, the factor has been shown to
      be an epithelial morphogen and also has antiproliferative effects in some cancer
      cell lines. The membrane receptor for hepatocyte growth factor/scatter factor has
      been identified as the c-met proto-oncogene product.

PMID- 1365918
TI  - Mucins: structure, function, and associations with malignancy.
AB  - Mucins are a family of high molecular weight, highly glycosylated glycoproteins
      found in the apical cell membrane of human epithelial cells from the mammary
      gland, salivary gland, digestive tract, respiratory tract, kidney, bladder,
      prostate, uterus and rete testis. Increased synthesis of the core protein and
      alterations in the carbohydrates attached to these glycoproteins are believed to
      play important roles in the function and proliferation of tumour cells. Aberrant
      glycosylation leads not only to the production of novel carbohydrate structures,
      but also to the exposure of the core peptide. These novel epitopes may be
      candidates for diagnosis or therapy, by using either synthetic mucin fragments as
      vaccines, or monoclonal antibody-based reagents which detect these structures.

PMID- 1365919
TI  - Origins of the gonadal mesoderm in Drosophila.

PMID- 1365920
TI  - Reverse genetics of Caenorhabditis elegans.
AB  - It is somewhat ironic that animals that are the prime choice for detailed genetic
      analysis, such as the fruit fly and the nematode, have thus far been largely
      refractory to reverse genetic analysis. Their detailed genetic map, and small
      genome size have made them subjects of ambitious genome analysis projects, but
      there is still no strategy to introduce desired changes into their genomes by
      homologous recombination. Some alternative approaches have recently become
      available; this review describes possibilities and unsolved problems for reverse
      genetics in the nematode Caenorhabditis elegans. The transposon Tc1 could prove
      to be very useful for the isolation of knock out mutants, and possibly also for
      introduction of more subtle alterations.

PMID- 1365921
TI  - Cell transplantation and gene therapy in muscular dystrophy.
AB  - Duchenne's muscular dystrophy (DMD), which affects 1/3500 live male births,
      involves a progressive degeneration of skeletal and cardiac muscle, leading to
      early death. The protein dystrophin is lacking in DMD and present, but defective,
      in the allelic, less severe, Becker muscular dystrophy and is also missing in the
      mdx mouse. Experiments on the mdx mouse have suggested two possible therapies for
      these myopathies. Implantation of normal muscle precursor cells (mpc) into mdx
      skeletal muscle leads to the conversion of dystrophin-negative fibres to 
      positive, with consequent improvement in muscle histology. Direct injection of
      dystrophin cDNA into skeletal or cardiac muscle also gives rise to dystrophin
      positive fibres. Although both appear promising, there are a number of questions
      to be answered and refinements to be made before either technique could be
      considered possible as treatments for myopathies in man.

PMID- 1365922
TI  - Psychiatrists in the new NHS.

PMID- 1365923
TI  - Paradoxical bronchoconstriction and salmeterol.

PMID- 1365924
TI  - [Medicine in visual and literary arts].

PMID- 1365925
TI  - [Intervertebral disk degeneration--a central cause of back problems].

PMID- 1365926
TI  - [Confirmation of parathyroid disease by hormone samples obtained with
      ultrasonography-guided technique].

PMID- 1365927
TI  - [Are insulin and triglycerides involved in clogging of arteries?].

PMID- 1365928
TI  - [Selective termination of multi-fetal pregnancies--an unavoidable consequence of
      treating infertility].

PMID- 1365929
TI  - [Treatment of facial spasm using botulinum toxin].

PMID- 1365930
TI  - [Are arterial aneurysms hereditary?].

PMID- 1365931
TI  - [Arrhythmogenic right ventricular dysplasia and idiopathic tachycardia].

PMID- 1365932
TI  - [Ascites as the first symptom of Felty syndrome in a woman with long-term
      rheumatoid arthritis].

PMID- 1365934
TI  - [Alternatives in alternative medicine--3 myths].

PMID- 1365933
TI  - [Status epilepticus--a problem in emergency medicine].

PMID- 1365935
TI  - [Problems in the fetus of diabetic mothers].

PMID- 1365936
TI  - [Changes in tumor suppressor genes as a mechanism in causing cancer].

PMID- 1365937
TI  - [Brain abscess].

PMID- 1365938
TI  - [Ultrasonography with vein compression in the diagnosis of deep venous
      thrombosis].

PMID- 1365939
TI  - [Does Helicobacter pylori cause stomach cancer?].

PMID- 1365940
TI  - [Myocardial stunning].

PMID- 1365941
TI  - [Alcohol and osteoporosis].

PMID- 1365942
TI  - [Temporary paralysis in a 17-year-old body-builder].

PMID- 1365944
TI  - [Damage to the medial cutaneous nerve of the forearm due to removal of
      contraceptive capsule or performance of other surgical procedure].

PMID- 1365943
TI  - [Shunt nephritis--an insidious kidney disease].

PMID- 1365945
TI  - [Histiocytes can also deplete health care resources].

PMID- 1365946
TI  - [Adolescent medicine].

PMID- 1365947
TI  - [Adolescent medicine today].

PMID- 1365948
TI  - [Neither child nor adult].

PMID- 1365949
TI  - [Rights of an adolescent].

PMID- 1365950
TI  - [Examination of an adolescent].

PMID- 1365951
TI  - [Too much too early].

PMID- 1365952
TI  - [Too fat or too thin].

PMID- 1365953
TI  - [Impact of childhood illness on the psychological development of a young person].

PMID- 1365954
TI  - [Adolescent sexuality].

PMID- 1365955
TI  - [Developmental delay in a boy].

PMID- 1365956
TI  - [Adolescent gynecological problems].

PMID- 1365957
TI  - [Adolescent psychological development curves].

PMID- 1365958
TI  - [Possibilities for disabled adolescents].

PMID- 1365959
TI  - [Effect of parents' divorce on adolescent development].

PMID- 1365960
TI  - [Open Doors].

PMID- 1365961
TI  - [A wall in front of you].

PMID- 1365962
TI  - [Multidrug resistance in the treatment of cancer].

PMID- 1365963
TI  - [Will the difference in incidence of coronary artery disease between East and
      West remain in Finland in the future?].

PMID- 1365964
TI  - [Varicocele--a treatable cause of infertility].

PMID- 1365965
TI  - [Will ultrasonography replace gynecologic examination?].

PMID- 1365966
TI  - [Calcium channel blockers and mild congestive heart failure: advantage or
      disadvantage?].

PMID- 1365967
TI  - [Epilepsy drugs in the treatment of manic disorders].

PMID- 1365968
TI  - [Changes in cholecystectomy].

PMID- 1365969
TI  - [A father with startle disease and a stiff newborn infant].

PMID- 1365970
TI  - [Carotid artery dissection].

PMID- 1365971
TI  - [Control of pain during labor].

PMID- 1365972
TI  - [Opinion on the drug treatment of peptic ulcer].

PMID- 1365973
TI  - [The mystery of neurotrophic factor receptor is being solved].

PMID- 1365974
TI  - [Rehabilitation of a patient with MS disease].

PMID- 1365975
TI  - [Health care of refugees].

PMID- 1365976
TI  - [Neuropeptide Y: a new peptide regulating behavior].

PMID- 1365977
TI  - [Quality of life following surgically treated cerebral hemorrhage].

PMID- 1365978
TI  - [Are there differences in lipid distribution between subjects with or without
      heart infarction?].

PMID- 1365979
TI  - [Severe asthma attack induced by propranolol].

PMID- 1365980
TI  - [Fever, convulsions, loss of consciousness and death of a girl with no previous
      health problems].

PMID- 1365982
TI  - [Experiences of dying at home].

PMID- 1365981
TI  - [Fundus oculi findings in a surgical patient with systemic candidiasis].

PMID- 1365983
TI  - [Continuous subcutaneous infusion of drugs in patients with advanced malignant
      disease].

PMID- 1365984
TI  - [Duplicate publications or service to Finnish readers].

PMID- 1365985
TI  - [Diagnostic criteria of MS disease].

PMID- 1365986
TI  - [The clinical picture of MS disease is now more complete].

PMID- 1365987
TI  - [Incidence, course and prognosis of MS disease].

PMID- 1365988
TI  - [Abnormalities in the immune system of MS patients and possibilities of
      immunological treatment].

PMID- 1365989
TI  - [Bladder dysfunction and sexual dysfunction and their management in patients with
      MS disease].

PMID- 1365990
TI  - [Prevention of brain damage during heart surgery].

PMID- 1365991
TI  - [Clinical aspects and prognosis of brain injury following heart surgery].

PMID- 1365992
TI  - [Acetaldehyde and proteins--the clinical significance of binding].

PMID- 1365993
TI  - [Bone transplantation].

PMID- 1365994
TI  - [Retinoblastoma--eye disease with diversity].

PMID- 1365995
TI  - [Involuntary treatment--deprivation of freedom or necessary treatment?].

PMID- 1365996
TI  - [Do antinuclear antibodies precede systemic lupus?].

PMID- 1365997
TI  - [Relapsing polychondritis in the lower respiratory tract].

PMID- 1365998
TI  - [Cutaneous malacoplakia in a patient with kidney transplantation].

PMID- 1365999
TI  - [Pneumocystis carinii infection in a patients with LED].

PMID- 1366001
TI  - [DNA has conquered the planet].

PMID- 1366000
TI  - [Joint symptoms, paraplegia and variable central nervous system symptoms].

PMID- 1366002
TI  - [Treatment of hemifacial spasm].

PMID- 1366003
TI  - [Observations on chlorophenol-associated cancer risk in Karkola].

PMID- 1366004
TI  - [Aggression and violence].

PMID- 1366005
TI  - [Aggressive brain: a neurophysiologist's viewpoint].

PMID- 1366006
TI  - [Aggression and psychological development].

PMID- 1366007
TI  - [Sexuality, narcissism and violence].

PMID- 1366008
TI  - [The social background of violence in modern society].

PMID- 1366009
TI  - [The aggressive patient].

PMID- 1366010
TI  - [Aggression in psycho-organic brain diseases].

PMID- 1366011
TI  - [Incest and society].

PMID- 1366012
TI  - [Viewpoints in helping victims of violence].

PMID- 1366013
TI  - [Aggressive behavior in a child: systemic observation].

PMID- 1366014
TI  - [Breaking the circle of aggression: victim, aggressor and network].

PMID- 1366015
TI  - [Problem of predicting violent behavior].

PMID- 1366016
TI  - [Violent patients: physician and law].

PMID- 1366017
TI  - [Psychoanalyst, inner self and the era of nuclear power].

PMID- 1366018
TI  - Heparin binding site, conformational change, and activation of antithrombin.
AB  - Alignment of the heparin-activated serpins indicates the presence of two binding
      sites for heparin: a small high-affinity site on the D-helix corresponding in
      size to the minimal pentasaccharide heparin, and a longer contiguous low-affinity
      site extending to the reactive center pole of the molecule. Studies of the
      complexing of antithrombin and its variants with heparin fractions and with
      reactive center loop peptides including intermolecular loop-sheet polymers all
      support a 3-fold mechanism for the heparin activation of antithrombin. Binding to
      the pentasaccharide site induces a conformational change as measured by circular
      dichroism. Accompanying this, the reactive center becomes more accessible to
      proteolytic cleavage and there is a 100-fold increase in the kass for factor Xa
      but only a 10-fold increase for thrombin, to 6.4 x 10(4) M-1 s-1. To obtain a 100
      fold increase in the kass for thrombin requires in addition a 4:1 molar ratio of
      disaccharide to neutralize the charge on the extended low-affinity site. Full
      activation requires longer heparin chains in order to stabilize the ternary
      complex between antithrombin and thrombin. Thus, addition of low-affinity but
      high molecular weight heparin in conjunction with pentasaccharide gives an
      overall kass of 2.7 x 10(6) M-1 s-1, close to that of maximal heparin activation.

PMID- 1366019
TI  - [Does corrosion ruin endoprostheses?].

PMID- 1366020
TI  - [Portrait of an arsonist].

PMID- 1366021
TI  - [Challenges and concerns in early-phase clinical trials].

PMID- 1366022
TI  - [Prognosis of rheumatoid arthritis in childhood].

PMID- 1366023
TI  - [Do Finnish melanoma patients have dysplastic nevi?].

PMID- 1366024
TI  - [Carnitine deficiency and severe nausea-induced thiamine deficiency causing a
      metabolic crisis].

PMID- 1366025
TI  - [Sinus arrest in a patient with sleep apnea syndrome associated with an increase
      in alertness].

PMID- 1366026
TI  - [Permanent colostomy].

PMID- 1366027
TI  - [Impotence, diabetes and liver disease].

PMID- 1366028
TI  - [Managers study and coronary heart diseases].

PMID- 1366030
TI  - [Treatment of arrhythmias using catheter ablation].

PMID- 1366029
TI  - [Women who had cesarean sections can have a vaginal delivery].

PMID- 1366031
TI  - [Localization of progressive myoclonus epilepsy gene opens new horizons for
      epilepsy research].

PMID- 1366032
TI  - [Pregnancy and heart disease].

PMID- 1366033
TI  - [Hematological isotope studies].

PMID- 1366034
TI  - [Lumbar spinal stenosis-associated functional disorders in pathways for tactile
      sensation and motor neurons].

PMID- 1366035
TI  - [The effect of lymphocyte homing receptors in the progression and prognosis of
      lymphoma].

PMID- 1366036
TI  - [Capricious ocular accommodation and convergence].

PMID- 1366037
TI  - [Fenestrated medial patella plica in siblings].

PMID- 1366038
TI  - [Anesthesia and hypokalemic periodic paralysis].

PMID- 1366039
TI  - [cryofibrinogenic purpura].

PMID- 1366040
TI  - [Falls in the elderly].

PMID- 1366041
TI  - [Physicians and driver's license].

PMID- 1366042
TI  - [Suspected deep venous thrombosis in the lower limb: ultrasound or non-ultrasound
      imaging?].

PMID- 1366043
TI  - [Can the Finnish immunization program be improved?].

PMID- 1366044
TI  - [Botulinum toxin, hope in the treatment of torticollis].

PMID- 1366045
TI  - ['Cephalosporinosis", an epidemic among Finnish physicians?].

PMID- 1366046
TI  - [Immunopathology of primary biliary cirrhosis].

PMID- 1366047
TI  - [Follow-up of laboratory costs].

PMID- 1366048
TI  - [Incidence and risk factors in acute otitis media in early childhood].

PMID- 1366049
TI  - [Incidence of urinary incontinence in adult Finnish women].

PMID- 1366050
TI  - [The sphenoidal electrodes in epilepsy].

PMID- 1366051
TI  - [Epidemic nephritis followed by hypogonadism].

PMID- 1366052
TI  - [In-vitro fertilization within the natural cycle].

PMID- 1366053
TI  - [Salmonella panama infection and meningitis in newborn infants].

PMID- 1366054
TI  - [Treatment and prevention of HIV infection and related opportunistic infections].

PMID- 1366055
TI  - [More about the cause of paresis].

PMID- 1366056
TI  - [Lipid hypothesis, true or not?].

PMID- 1366058
TI  - [Smoking as a trigger in heart infarction].

PMID- 1366059
TI  - [Renewed occurrence of Mycoplasma].

PMID- 1366057
TI  - Five specificity patterns of (1----3)-alpha-L-fucosyltransferase activity defined
      by use of synthetic oligosaccharide acceptors. Differential expression of the
      enzymes during human embryonic development and in adult tissues.
AB  - The use of synthetic trisaccharides as acceptors led to the definition of five
      main (1----3)-alpha-L-fucosyltransferase activity patterns in human adult
      tissues: (I). Myeliod cells, granulocytes, monocytes, and lymphoblasts, transfer
      an alpha-L-fucopyranosyl group to O-3 of a 2-acetamido-2-deoxy-D-glucosyl residue
      of H blood-group Type 2 oligosaccharide [alpha-L-Fucp-(1----2)-beta-D-Galp-(1---
      4)-beta-D-GlcpNAc----R] with Mn2+ as activator. (II) Brain has the same acceptor
      specificity pattern as myeloid cells, but can also use Co2+ as activator. (III)
      Plasma and liver transfer an alpha-L-furopyranosyl group to H blood-group Type 2
      and to sialyl-N-acetyllactosamine [alpha-NeuAc-(2----3)-beta-D-Galp-(1----4)-beta
      D-GlcpNAc----R]. (IV) Intestine, gall bladder, kidney, and milk have the same
      activity as (III), but also transfer an alpha-L-fucopyranosyl group to O-4 of a 2
      acetamido-2-deoxy-D-glucose residue of H blood-group Type 1 [alpha-L-Fucp-(1---
      2)-beta-D-Galp-(1----3)-beta-D-GlcpNAc----R] and sialyl Type 1 [alpha-NeuAc-(1---
      3)-beta-D-Galp-(1----3)-beta-D-GlcpNAc----R]. (V) Stomach mucosa is not able to
      use sialyl-N-acetyllactosamine, but can transfer an alpha-L-fucopyranosyl group
      to the other Type 1 and Type 2 acceptors. Unlike in adult tissue, a single
      myeloid-like pattern of (1----3)-alpha-L-fucosyltransferase activity was found at
      early stages of development in all tissues tested. This embryonic enzyme is later
      progressively replaced by enzymes or mixtures of enzymes having the corresponding
      adult patterns of enzyme expression. All lymphoblastoid cell lines and half of
      the tumor epithelial cell lines tested expressed the myeloid-like pattern of
      enzyme found in normal embryonic tissues. The remaining tumor epithelial cell
      lines expressed different forms of (1----3/4)-alpha-L-fucosyltransferase acceptor
      specificity patterns.

PMID- 1366060
TI  - [The effect of loading on articular cartilage].

PMID- 1366061
TI  - [Surgical treatment of Wolff-Parkinson-White syndrome].

PMID- 1366062
TI  - [Catatonia and neuroleptic malignant syndrome in a mentally retarded patient].

PMID- 1366063
TI  - [Osteomalacia associated with antacid abuse].

PMID- 1366064
TI  - [Treatment of tendinitis].

PMID- 1366065
TI  - [Treatment of hemifacial spasm].

PMID- 1366066
TI  - [Involuntary treatment].

PMID- 1366067
TI  - [Insulin resistance and blood circulation in muscles].

PMID- 1366068
TI  - [The role of drugs in the long-term management of cardiac arrhythmias].

PMID- 1366069
TI  - [Interpretation of research results using confidence interval].

PMID- 1366070
TI  - [Epithelial basement membrane MDF dystrophy of the cornea].

PMID- 1366071
TI  - [Outcome in the management of squamous cell skin carcinoma].

PMID- 1366072
TI  - [Purulent pericarditis].

PMID- 1366073
TI  - [Management of penile incarceration].

PMID- 1366074
TI  - [Diagnosis and treatment of acute hemarthrosis of the knee].

PMID- 1366076
TI  - [Management of obesity--a physician's blind spot].

PMID- 1366075
TI  - [Prolonged fever and acute hematemesis in a girl with acute leukemia].

PMID- 1366077
TI  - [Initiation of treatment of diabetes in children].

PMID- 1366078
TI  - [What do mortality studies teach about the treatment of arthritis?].

PMID- 1366079
TI  - [Youths and suicide].

PMID- 1366081
TI  - [Stargardt's disease--ocular findings and family studies in Finnish patients].

PMID- 1366080
TI  - [Oxidant and antioxidant properties of lung cells].

PMID- 1366082
TI  - [Live kidney donors in Finland in the years 1982-1990].

PMID- 1366083
TI  - [Epileptic seizures during clozapine treatment].

PMID- 1366084
TI  - [Streptococcus zooepidemicus sepsis in an elderly woman].

PMID- 1366085
TI  - [Pelvic inflammatory disease and its treatment].

PMID- 1366086
TI  - [The use of impact factors in assessing the quality of international journals].

PMID- 1366087
TI  - [Pillows and otitis media].

PMID- 1366088
TI  - [Gene technology and current possibilities for pharmacological intervention].

PMID- 1366089
TI  - [Familial hypercholesterolemia--from gene defect to cholesterol accumulation].

PMID- 1366090
TI  - [Familial hypercholesterolemia: treatable receptor disease].

PMID- 1366092
TI  - [Bronchial hyperreactivity in young patients with asthma].

PMID- 1366091
TI  - [Skin changes in the vulvar area].

PMID- 1366093
TI  - [Peripheral myopathies in Finland--a new kind of muscular dystrophy in the leg].

PMID- 1366094
TI  - [Inherited thrombocytopenias].

PMID- 1366095
TI  - [Diagnosis and treatment of urinary tract infections in children].

PMID- 1366096
TI  - [Sudden decrease in vision].

PMID- 1366097
TI  - [Fat consumption and male mortality in coronary heart disease].

PMID- 1366098
TI  - [Misleading lipid hypothesis].

PMID- 1366100
TI  - [Molecular genetics of aspartylglucosaminuria].

PMID- 1366099
TI  - Varicella-zoster virus open reading frame 61 protein is functionally homologous
      to herpes simplex virus type 1 ICP0.
AB  - The varicella-zoster virus (VZV) open reading frame 61 (ORF61) protein is thought
      to be the homolog of herpes simplex virus type 1 (HSV-1) ICP0, based on gene
      location and limited amino acid homology. However, HSV-1 ICP0 trans activates HSV
      1 genes, while VZV ORF61 protein trans represses the function of VZV trans
      activators on VZV promoters in transient expression assays. To investigate the
      functional relatedness of HSV-1 ICP0 and VZV ORF61 protein, we established Vero
      and MeWo cell lines which stably express VZV ORF61 under the control of a
      metallothionein promoter and performed complementation studies with an HSV-1 ICP0
      deletion mutant (7134). Mutant 7134 is impaired for plaque formation and
      replication at a low multiplicity of infection in cell culture, but these defects
      were complemented by up to 200-fold in Vero cell lines expressing VZV ORF61.
      Likewise, the efficiency of plaque formation was improved by up to 100-fold in
      MeWo cell lines expressing VZV ORF61. A cell line expressing another VZV
      immediate-early gene product (ORF62) was unable to complement mutant 7134. HSV-1
      mutants which are deleted for other HSV-1 immediate-early gene products (ICP4,
      ICP27) were unable to grow in VZV ORF61-expressing cell lines. These results
      indicate that, despite marked differences in their sequences and in effects on
      their cognate promoters in transient expression assays, VZV ORF61 protein is the
      functional homolog of HSV-1 ICP0.

PMID- 1366101
TI  - [Special cardiological studies in the evaluation of syncope].

PMID- 1366102
TI  - [Using nutrition to improve the results of endurance training in athletes].

PMID- 1366104
TI  - [Genetic screening--part of tomorrow's medicine].

PMID- 1366103
TI  - [Magnetic stimulation of the central nervous system as an aid in
      neurophysiology].

PMID- 1366105
TI  - [Infections of tooth attachment tissues and their treatment].

PMID- 1366106
TI  - [Collagenase inhibition by tetracyclines].

PMID- 1366107
TI  - [Nobel prize in chemistry to Richard Ernst].

PMID- 1366108
TI  - [Flumazenil-induced contractile seizure in poisoning by a combination of
      tricyclic antidepressants and benzodiazepine in a young woman].

PMID- 1366109
TI  - [Cardiac tamponade as the initial symptom of malignant tumor].

PMID- 1366110
TI  - [Cow's milk allergy as a cause of urticaria and angioedema].

PMID- 1366112
TI  - [Can "Spanish disease" repeat itself?].

PMID- 1366111
TI  - [Hirudin--comeback of Hirudo medicinalis].

PMID- 1366113
TI  - [Ultrasound and Doppler studies in the detection of and screening for ovarian
      cancer].

PMID- 1366114
TI  - [Problems in cyclosporin medication].

PMID- 1366115
TI  - [Limb ischemia and mitral valve defect as complication of migraine medication].

PMID- 1366116
TI  - [Are balloons dangerous?].

PMID- 1366117
TI  - [Can muscular dystrophy be treated?].

PMID- 1366118
TI  - [Mitochondrial diseases].

PMID- 1366120
TI  - [Rehabilitation of children with muscular disorders].

PMID- 1366119
TI  - [[Study of dystrophin in muscular dystrophy--why and when?].

PMID- 1366121
TI  - [Short stature and calcium deposits in the brain of an 8-year-old girl].

PMID- 1366122
TI  - [When should endoscopic cholecystectomy be carried out?].

PMID- 1366123
TI  - [Psychosocial factors and breast cancer].

PMID- 1366124
TI  - [Osteochondrosis dissecans in the knee joint].

PMID- 1366125
TI  - [Eosinophilic pneumonia].

PMID- 1366126
TI  - [Importance of ultrasonographic findings of the brain in terms of evaluating the
      outcome of premature newborn infants].

PMID- 1366128
TI  - [Familial benign hypercalcemia--cause for needless parathyroid surgery].

PMID- 1366127
TI  - [Thyroid nodule and its study in Finland].

PMID- 1366129
TI  - [Status epilepticus following propofol anesthesia].

PMID- 1366131
TI  - [Spontaneous dissection of the internal carotid artery].

PMID- 1366130
TI  - [Asthma and gastroesophageal reflux].

PMID- 1366132
TI  - [Carotid artery dissection].

PMID- 1366133
TI  - Quinolone antibacterial agents. Synthesis and structure-activity relationships of
      a series of amino acid prodrugs of racemic and chiral 7-(3-amino-1
      pyrrolidinyl)quinolones. Highly soluble quinolone prodrugs with in vivo
      pseudomonas activity.
AB  - A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)
      6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3
      quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids,
      and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been
      prepared and evaluated for comparative antibacterial activity. Compounds were
      prepared by acylation of the 3-amino group of the pyrrolidine with common amino
      acids using standard peptide chemistry. This series has been compared with the
      parent compounds for antibacterial activity in vitro and in vivo as well as for
      comparative solubility. The amino acid analogues were less active in vitro, but
      had equal or increased efficacy in vivo. Indeed, it was proven that these
      compounds, which were stable to acid and base under the reaction conditions for
      their preparation, were rapidly cleaved in serum to give the parent quinolones.
      The amino acid derivatives showed a 3-70 times improved solubility when compared
      to the parent compounds. The most active compound of the series was [S-(R*,R*)]-7
      [3-[(2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1- cyclopropyl-6-fluoro-1,4
      dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).

PMID- 1366134
TI  - Mallory-Weiss tears occurring during endoscopy: a report of seven cases.
AB  - Mallory-Weiss tears occurring during the course of upper gastrointestinal
      endoscopy are apparently rare. The present report describes seven cases of
      iatrogenic gastro-oesophageal tears encountered during 10,000 endoscopic
      examinations over a period of six years. Five of the seven patients were female
      and six patients were aged 75 years or older. Six patients had hiatal hernias.
      The site of the mucosal tear was similar in all patients, extending from a V
      shaped breach at the gastro-oesophageal junction inferiorly along the lesser
      curve for a variable distance of up to 8 cm. Neither retching nor struggling
      during the procedure contributed to the development of the lesion in any of the
      patients. One patient suffered from a haematemesis which required transfusion,
      and in a further patient the tear resulted in a haematemesis and gastric
      perforation necessitating laparotomy. The study indicates that Mallory-Weiss
      tears complicating endoscopy occur especially in elderly, female patients with
      hiatal hernias. The importance of admitting patients with this complication to
      hospital for overnight observation is recommended in view of the possible
      development of haemorrhage or perforation.

PMID- 1366135
TI  - [Primary leiomyosarcoma of the left renal vein].
AB  - The authors report a case of leiomyosarcoma of the left renal vein. Because of
      its retroperitoneal position, this exceptional tumour was responsible for few
      symptoms. Complementary investigations (CT scan, ultrasonography, arteriography)
      often do not confirm the diagnosis. Complete surgical excision combined with
      complementary treatment can ensure long-term survival.

PMID- 1366136
TI  - Proceedings of the 9th International Symposium on Microsomes and Drug Oxidations.
      Jerusalem, Israel, July 6-9, 1992. Abstracts.

PMID- 1366137
TI  - [Rheumatic complaints and diseases in ex-prisoners of war in Croatia in 1991. A
      review of medical prognosis for work capacity].
AB  - The results are presented of an examination of the locomotor system in 48 ex
      prisoners of war, previously maltreated in prison camps in Serbia and occupied
      areas of Croatia. They were part of a group of 508 prisoners of war, examined in
      the Clinic for Infectious Diseases in Zagreb. They were all male, aged 33.9 +/-
      11.56 years, in whom, after the first medical examination a rheumatological
      examination was indicated because of disorders of the locomotor system. Only
      16.7% of the subjects had not been physically maltreated. Blows to the lumbo
      sacral spine were the most frequent (43.7%), shoulders (33.4%) and the head
      (27.0%). Earlier rheumatic disorders were reported by 41.7% of the ex prisoners,
      and during the examination in our Rheumatological clinic 70.8%. In 21% of the ex
      prisoners the rheumatological disorders started as a direct consequence of
      maltreatment in the prison camps. In one of the ex-prisoners acquisition of
      ankylosis spondylitis occurred and in another uric arthritis. In 50% of the ex
      prisoners a marked reduction in work ability was confirmed. Disability retirement
      was proposed for two ex-prisoners. Optimal health treatment is discussed and
      medical prognosis of work ability.

PMID- 1366138
TI  - [The effect of gold salts on rheumatoid factor dynamics in patients with
      rheumatoid arthritis].
AB  - The aim of research was to establish effect of gold-salts (under protected name
      "Tauredon" Byk Gulden) on the dynamics of rheumatoid factor, decreed with Waaler
      Rose test, at patients with rheumatoid arthritis. Following the dynamics of
      rheumatoid factors was performed during 6 months continued application of
      "Tauredon" on a group of patients with certain diagnosis of rheumatoid arthritis.
      The group consisted of 8 men and 35 women, with age profile of 50 years. With
      continuous observation of patients and their laboratory findings (Waaler-Rose
      test) in regular time intervals it was found out that "Tauredon" has significant
      influence on oscillation of rheumatoid factor, decreed by the method of
      hemaglutination of sheep erythrocytes.

PMID- 1366139
TI  - [Radiologic changes in the costovertebral and costotransverse joints and
      functional changes in the thoracic spine in ankylosing spondylitis].
AB  - Radiological, morphological and functional changes of the thoracic spine together
      with costovertebral and costotransversal joint involvement were studied in
      patients with ankylosing spondylitis. While radiological changes were found in
      all patients, in 74% they were of inflammatory origin. Radiological abnormalities
      were more prominent in patients with a more severe clinical course and a
      relatively short duration of the disease. As many as 95% of patients exhibited
      functional impairment of the thoracic spine. No significant difference was
      observed between the duration of disease and functional impairment of the
      thoracic spine (t = 1.4, P > 0.05) but there was a highly significant correlation
      between radiological changes and functional impairment of the thoracic spine (r =
      0.577, P < 0.001).

PMID- 1366140
TI  - [The effect of Tauredon on the development of non-specific indicators of
      inflammatory activity in patients with rheumatoid arthritis].
AB  - The objective of this research has been to determine the effects of the gold
      salts Tauredon Byk Gulden on the development of non-specific parameters with
      regard to the inflammatory processes in patients with rheumatoid arthritis. The
      group being tested comprised 8 men and 35 women with a positive diagnosis of
      rheumatoid arthritis, their average age being 50, the average disease course 9.5
      years. During a six-month continuous application of Tauredon, the following
      parameters were observed in regular intervals: the erythrocyte sedimentation
      rate, the haemoglobin level in the serum and the C-reactive protein. The
      statistical processing of data indicated that Tauredon significantly reduces the
      erythrocyte sedimentation, considerably increases the haemoglobin level in the
      serum and significantly decreases the C-reactive protein value.

PMID- 1366141
TI  - [Critical review of images of the lumbosacral part of the spine in patients with
      low back pain].
AB  - A comparative analysis of X-ray images of lumbar spine both in the standard
      positions (dorsal and profile image) and upright position has been performed by
      the authors. The examination was carried--out on 33 subjects in all (17 man and
      16 women). The sagital curvature of lumbar spine changes considerably in
      dependence of body position during the raying. Preserved lumbar lordosis was
      found in 31 patients X-ray images take in upright position or 94%, while lumbar
      lordosis in standard position was seen reduced or completely disappeared in X-ray
      images. The evaluation of sagital curvature degree is of almost importance in
      physiotherapy due to correct planning kinesiotherapeutic procedure. Only the X
      ray images of an observed group patients in a upright position was showed the
      spondylolisthesis in one patient, stenosis of lumbar spine channel in one patient
      and the lesion of intervertebral disc in one patient. The authors conclude that
      in patients with low back pain syndrome only the X-ray images in upright position
      are necessary, since they provide more information to analyse both the condition
      and the relation between the vertebral dynamical segments.

PMID- 1366142
TI  - [The effect of 6 months of treatment with Tauredon on clinical indicators in
      rheumatoid arthritis].
AB  - The objective of this research has been to evaluate the efficacy of Tauredon (the
      aqueous solution of Na-thiomalate) on the development of some clinical parameters
      in patients with rheumatoid arthritis. The group being tested comprised 8 men and
      35 women, their average age being 50, the average duration of their illness being
      9.5 years. As regards the anatomic development stage of illness, the majority of
      patients belonged to stage 2 (62.8%), with no patients belonging to stage 4.
      During the continuous six-month application of Tauredon, the following parameters
      have been observed: the Ritchie index, the PIP extent of the fist joints and the
      morning stiffness span of the small fist joints. The evaluation of the six-month
      treatment with Tauredon has proved its positive effect on all clinical
      parameters, shown in the lower value of the Ritchie index, the lower PIP extent
      of the fist joints as well as the shorter morning stiffness span. Further, the
      Tauredon effect has been seen in suppressing the inflammatory activities and in
      restituting the joint functions in patients with rheumatoid arthritis.

PMID- 1366143
TI  - [Analysis of the type of hairiness in the early diagnosis of ankylosing
      spondylitis].

PMID- 1366144
TI  - [Complement (C3 and C4) in patients with rheumatoid arthritis during 6 months of
      treatment with gold salts].
AB  - The aim of research was to establish effect of gold-salts under protected name
      "Tauredon" Byk Gulden, on the dynamics of fraction of complements C3 and C4 at
      patients with rheumatoid arthritis. Following the dynamics of both parameters,
      was performed during 6 months continued application of "Tauredon", on 8 men and
      35 women with certain diagnosis. Profile of the age of patients was 50 years old.
      With continuous observation of patients and their laboratory findings, in regular
      time intervals, we found out that "Tauredon" has significant influence on
      increase of level of C3 in serum of patients (P = 0.006) but not in increase of
      fraction of complement C4 (P = 0.117).

PMID- 1366145
TI  - [The effect of Na-aurothiomalate on circulating immune complex dynamics in
      patients with rheumatoid arthritis].
AB  - The objective of this research has been to determine the efficacy of Na
      aurothiomalate, under the trade name Tauredon, on the development of circulating
      immune complexes (CIC) in patients with rheumatoid arthritis. During a continuous
      six month administering of Tauredon to a group of patients with the diagnosis of
      rheumatoid arthritis various parameters have been observed. The group comprised
      43 patients, 8 men and 35 women, their average age being 50. By continuous
      observations of both the patients and their laboratory reports in regular
      intervals during six-month administering of Tauredon, a positive effect of
      Tauredon on the development of the CIC IgM values (P = 0.006) has been proved,
      i.e. reducing their level in the patients' serum. Owing to great individual
      differences in the decrease of the CIC IgG values, it has been difficult to prove
      the consequences of this fall (P = 0.086). The impossibility of testing the
      significant decrease of the CIC IgA values is due to a small number of patients
      with the positive CIC IgA values.

PMID- 1366146
TI  - [Prevalence of rheumatoid factor in a single sampling of the urban population in
      Croatia].
AB  - The prevalence of rheumatoid factor (RF) in urban population was examined. A
      random sample was taken according to the register of voters and included 5% of
      the population. Among them 60% suffered from various rheumatic symptoms. Out of
      500 persons invited to an examination, 231 examinees responded. None of the
      examinees in that moment showed signs of rheumatoid arthritis. RF is determined
      in serum according to Waaler-Rose and it was positive in 12 out of 231 examinees
      (5.2%) about equally in men and women (P > 0.05). The majority of examinees was
      over 50 years old. Titar RF increased with the age of the examinee, but
      difference is not significant (P > 0.05). RF is not only a characteristic of RA,
      but it could also be found during the other diseases which are accompanied by,
      first of all, hypergammaglobulinemia and fibrosis.

PMID- 1366147
TI  - [Phagocytic activity in rheumatoid arthritis].
AB  - The phagocytic activity of leukocytes was studied in 41 patients with active
      rheumatoid arthritis, 24 of whom were treated with gold compounds and the
      remaining 17 with non-steroidal anti-inflammatory drugs. The control group
      comprised 137 patients with no signs of inflammatory rheumatic diseases. The mean
      age of patients was 54.8 years (range: 32-75) and that of the controls, 53.5
      years (range: 32-75). Spontaneous mobility (P < 0.001), phagocytic activity (P <
      0.001) and antibody-dependent cytotoxicity (P < 0.001) of leukocytes were
      significantly lower in patients with rheumatoid arthritis compared to the control
      group. No significant differences were observed between patients treated with
      gold compounds and those receiving nonsteroidal anti-inflammatory drugs with
      respect to mean spontaneous mobility (U = 198, P = 0.44), phagocytic activity (U
      = 185, P = 0.31) and antibody-dependent cytotoxicity (U = 183, P = 0.29) of
      leukocytes. Among patients treated with gold compounds phagocytic activity was
      significantly lower in those receiving TauredonR compared to those receiving
      AuropanR (U = 33.5, P = 0.05). The antibody-dependent cytotoxicity was comparable
      in patients receiving Tauredon and Auropan, respectively (U = 58.5, P = 0.48).

PMID- 1366148
TI  - [Systemic allergic vasculitis: case report of a female patient with the Churg
      Strauss syndrome].
AB  - A female patient with asthmatic attacks developed signs of peripheral and central
      nervous system involvement, cutaneous and joint manifestations, pulmonary and
      gastrointestinal involvement, with significant body weight loss. A blood
      eosinophilia was found and muscle biopsy revealed tissue infiltration by
      eosinophils and vasculitis. Very short interval from onset of first symptoms to
      appearance of vasculitis is a bad prognostic sign and probably cause of
      unsuccessful therapy.

PMID- 1366149
TI  - [Side effects of gold salt therapy in patients with rheumatoid arthritis].
AB  - Observing the efficacy of the gold sodium thiomalate (under the trade name of
      Tauredon Byk Gulden) during the treatment of 43 patients with rheumatoid
      arthritis, a certain number of side effects have been noted and registered. The
      group being tested comprised 43 patients, 8 men and 35 women, average age being
      50. The side effects were observed in 14 patients (32.5%), namely in one man and
      13 woman, the most frequent being thrombocytopenia (20.8%), serious exacerbation
      of the disease (16.6%), thrombocytosis and dermatitis (12.5%). The recurrence
      rate of the side effects during the treatment with the gold sodium thiomalate was
      greater during the first (14%) and the second month (11.8%) than during the third
      (4.6%) and the fourth month (2.5%).

PMID- 1366150
TI  - [Educational-motivational guidelines for working with parents of children with
      juvenile chronic arthritis].
AB  - This paper points at the role of parents in performance and supervision of out
      institutional treatment and rehabilitation of children suffering from juvenile
      chronic arthritis (JCA) dealing with educational--motivating elements in work of
      parents with ill child. Medical psycho-sociological and pedagogic aspects of work
      of parents with ill child has been presented. For each indicated educational-
      motivating unity parents have to be completely prepared for better and more
      complete than usual piling of facts and presenting in front of them unsolvable
      tasks and obligations. Should child's rheumatologist succeed in this a plan of
      individual continuous treatment and rehabilitation of each patient suffering from
      JCA shall meet with success.

PMID- 1366151
TI  - [Results of a comparative study of the success of treatment of pain in the lumbar
      spine at the Moravske Toplice health spa, at the department of physical therapy
      and rehabilitation and at the department of rheumatology of the Maribor Teaching
      Hospital].
AB  - A parallel investigation of the success of treating patients with chronic low
      back pain has been carried out at the Moravci Spa, at the Department for Physical
      Therapy and Rehabilitation and at the Rheumatology Department of Maribor Teaching
      Hospital. One hundred patients suffering from low-back pain were given a 14-day
      treatment in the termomineral water (T--36 degrees C) of the Moravci Spa. A
      comparative group of another 100 patients also suffering from pain in the lumbar
      region of the spine underwent equal balneo-physical treatment in plain water (T-
      32 degrees C) at the Dept. for Physical Therapy and Rehabilitation and at the
      Dept. of Rheumatology at Maribor Teaching Hospital, Slovenia. The educational
      background of the two groups features a statistically significant difference (p <
      0.001): the percentage of patients with lower education was higher at the Moravci
      Spa (67%) compared with only 46% among those treated at Maribor Teaching
      Hospital. Correspondingly, the difference in occupation of the two groups were
      similar (p < 0.005): prevalent among the patients at Moravci Spa were bluecollar
      workers (40%) compared with white-collar workers (27%). The percentage of white
      collar workers at Maribor Teaching Hospital was 45%. The average age of the
      patients treated at the Moravci Spa was 46.9 +/- 9.5 years (28-77 years), at
      Maribor Teaching Hospital it was 45.2 +/- 8.2 years (26-71 years). There was no
      statistically significant difference in age (p < 0.10) between the two groups.
      Generalized spondylochondrosis was present in both groups, i.e. 87%;
      approximately 10% of the patients from both groups underwent surgical treatment
      of hernia disci.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1366152
TI  - [The effect of verticalization of the resulting force (R) of weight bearing in
      the hip joint on morphologic characteristics of the medullary canal in the
      femoral shaft in patients with coxarthrosis].
AB  - An influence of verticalization of the resulting force of weight-bearing on the
      hip joint "R" on the morphological characteristics of the medullar canal on the
      proximal edge of the shaft of femur was researched. Progressive degenerative
      changes of the hip joint with a consequent sideways limping or changes of the
      collodiaphysial angle (ccd angle) were the cause of the verticalization of the
      resulting force "R". The analysis of patients treated and operated on The
      Orthopaedic Department of the General Hospital Osijek and The Orthopaedic Clinic
      of The Medical Faculty of The University of Zagreb. The research, undoubtedly,
      proved that the patients with coxarthrosis and side-ways in the hip or with
      changed collodiaphysial angle experienced verticalization of the resulting force
      of weigh-bearing of the hip joint and the proximal edge of femur which caused
      morphological changes of the medular canal of the shaft of femur.

PMID- 1366153
TI  - Seat belts in pregnancy.

PMID- 1366154
TI  - [How does short-term ischemia protect the heart?].

PMID- 1366155
TI  - [The prognostic value of antinuclear antibodies in rheumatic diseases].

PMID- 1366156
TI  - [Clinical and histomorphometric methods in the assessment of prognosis in breast
      cancer].

PMID- 1366157
TI  - [Khat--a new drug in Finland].

PMID- 1366158
TI  - [Social status, risk factors and mortality in coronary heart disease in men and
      women in Eastern Finland].

PMID- 1366159
TI  - [Pulmonary thromboendarterectomy in the treatment of pulmonary hypertension].

PMID- 1366160
TI  - [Treatment of early-stage asthma].

PMID- 1366162
TI  - [Prevention and treatment of osteoporosis].

PMID- 1366161
TI  - [Cyclosporin treatment].

PMID- 1366163
TI  - [It is beneficial to treat systolic hypertension in the elderly].

PMID- 1366164
TI  - [Discovery of the gene defect in fragile X syndrome reveals a new mode of
      inheritance and improves diagnosis].

PMID- 1366165
TI  - [Complex mechanics of tumor-necrosis-factor-induced cell death].

PMID- 1366166
TI  - [Parturients in 1988].

PMID- 1366167
TI  - [Reactive arthritis caused by Salmonella].

PMID- 1366168
TI  - [Should an elderly patient with heart infarction be treated in a coronary care
      unit or on a general ward?].

PMID- 1366169
TI  - [Walking cast in the treatment of diabetic foot ulcer].

PMID- 1366170
TI  - [Long-term effects of farmer's lung--results of a 10-year follow-up study].

PMID- 1366172
TI  - [A Finnish thyroid nodule and its study].

PMID- 1366171
TI  - [Intrathoracic splenosis, an unusual cause of thoracic coin lesions].

PMID- 1366173
TI  - [Pediatric surgery].

PMID- 1366174
TI  - [Fetal surgery].

PMID- 1366175
TI  - [Pediatric microsurgery].

PMID- 1366176
TI  - [Hydrocephalus].

PMID- 1366177
TI  - [Bronchoscopy in newborn infants].

PMID- 1366179
TI  - [Upper gastrointestinal tract endoscopy in infants].

PMID- 1366178
TI  - [Heart surgery in newborn infants].

PMID- 1366180
TI  - [Surgical management of gastroesophageal reflux].

PMID- 1366181
TI  - [Appendicitis or not?].

PMID- 1366182
TI  - [Diagnosis and management of severe constipation in children].

PMID- 1366184
TI  - [Vesico-ureteral reflux].

PMID- 1366183
TI  - [Enuresis and urodynamics].

PMID- 1366185
TI  - [Hypospadias].

PMID- 1366186
TI  - [Bone nodules in children].

PMID- 1366187
TI  - [Methods of lower limb lengthening].

PMID- 1366188
TI  - [Neuromuscular scoliosis in children].

PMID- 1366189
TI  - [Pediatric organ transplantation in Finland].

PMID- 1366191
TI  - [How should patients with colorectal cancer be followed?].

PMID- 1366190
TI  - [Treatment of hyperlipidemia in patients with coronary heart disease].

PMID- 1366192
TI  - [Why does medical practice vary?].

PMID- 1366193
TI  - [Follow-up of cancer in patients with ulcerative colitis].

PMID- 1366194
TI  - [Coffee and health].

PMID- 1366196
TI  - [Risk of arrhythmia in long-acting H1-selective antihistaminics poisoning].

PMID- 1366195
TI  - [Regional variation in surgical procedures in Finland].

PMID- 1366197
TI  - [Sore throat and vertigo in herpes zoster oticus].

PMID- 1366198
TI  - [Management of Basedow's ophthalmopathy].

PMID- 1366199
TI  - [How is open-angle glaucoma diagnosed?].

PMID- 1366200
TI  - [Spironolactone, potassium chloride and hyperkalemia in patients with kidney
      failure].

PMID- 1366201
TI  - [Health research in the context of social policies].

PMID- 1366202
TI  - [A community program to stimulate smoking cessation].
AB  - A community program to stimulate smoking cessation developed on the 1988 World No
      smoking Day in the city of Barcelona (Spain) is presented. Participants in this
      program could make a written commitment to quit, and received support materials
      by mail. The results are evaluated in a sample of participants: 69% declare
      having quit on the specified date, and 29% do not smoke after one year.

PMID- 1366203
TI  - [A surveillance system on the risk of importing viral hemorrhagic fevers].

PMID- 1366204
TI  - [Socioeconomic level and mortality].
AB  - A revision of the bibliography has been carried out, referring to the influence
      of people's social economic condition to the cause and age at death. Special
      interest was taken in collecting works carried out after the Black Report was
      published, taking its particular relevance into account.

PMID- 1366205
TI  - [The revision of the organization of consultation for long-term treatment].
AB  - The growing drug dependency of developed societies has meant the uncontrolled use
      of drugs with the consequent medical risks and important economic repercussions.
      Primary health care in our country is characterized by high demand
      bureaucratization of clinics. Because of this, we consider it useful to rely on a
      prescription system for long term treatment, this being understood as a mechanism
      which allows the obtaining of prescriptions easily both for the patient and the
      doctor, control and monitoring of established chronic treatments, periodical
      therapy evaluations, which rely on the participation of other members of the
      primary health care team. In this report the model of the repeat prescription
      system in our health area is shown, from which the prescription can be obtained
      in a maximum time limit of 8 hours, the medication taken for chronic illness can
      be easily recognized and to make note of the date of the prescription.

PMID- 1366206
TI  - [The diagnosis of basic sanitation in the Erniobea region].
AB  - The aim of this report was to identify the basic sanitary situation and that of a
      series of health markers, in the area of influence of our health centre. The
      population studied have all come from places under the census and the measuring
      system used was a prepared survey and also, direct observation. The information
      collected was verified by revising all the clinical notes of the affected people.
      The results found are presented, referring to the characteristics of the houses
      and the stables, the sanitary situation of the livestock, water supply and
      excrement removal, rubbish removal methods and health markers. The high number of
      houses without adequate installation maintenance (water, excrement...) and the
      high incidence of infectious diseases should be highlighted.

PMID- 1366208
TI  - [Uniform requirements for manuscripts submitted to biomedical journals. The
      International Committee of Medical Journal Editors].

PMID- 1366207
TI  - [The ionic composition of the atmospheric aerosols in industrial areas of the
      north of Spain].
AB  - Over the years 1986, 1987 and 1988 determinations of the mass concentration of
      total particles in suspension and of the anionic components (chlorides, nitrates
      and sulphates) and cationic (sodium, potassium, calcium, magnesium and ammonia)
      contained in these was carried out in Bilbao, Sestao and Erandio. The
      determination of the mass of particles was carried out by gravimetry and chemical
      composition by ionic chromatography. The particle concentrations in Bilbao and
      Sestao, over the measuring period, were higher than those in Erandio. The studies
      of concentrations, percentages and correlations show the existence of centres of
      calcium emission during one season and high levels of chlorides during all of
      them. Surprisingly enough, the nitrate and ammonia content for all the seasons is
      low in comparison with other urban and industrial centres of the peninsular
      inland.

PMID- 1366209
TI  - [An epidemiological study of the body mass index in a school-aged population of
      Madrid].
AB  - FOUNDATION: A descriptive study has been carried out, to perform body mass index,
      between 2606 schoolchildren at Madrid, during 1986 to 1990. METHODS:
      Observational and transversal study. RESULTS: The data obtained were compared by
      age and sex for each year, and we calculated the body mass index percentiles for
      each group in the study. Mean body mass index rises with age and also 90 and 95
      percentiles. CONCLUSION: The 1.5% and 0.8% of children at 6 years had BMI more
      than 26, for male and female respectively. At age 10, this percentages were 9.5%
      and 11.6% for male and female, and the results for age 13 were 16.1% and 17.8%
      respectively.

PMID- 1366210
TI  - [The epidemiology of dermatologic diseases in primary care].
AB  - With the aim of finding out the prevalence and the origin of the skin disease in
      primary health care, a prospective study was carried out over the period of May
      to October of 1989 in an urban health centre, with the support of the
      dermatologist and using iconographic means. The 395 cases considered made up
      4.85% of all the medical examinations. A limited number of diagnoses (11) made up
      the majority of the medical examinations (70%). 19% were referred to the
      dermatologist. 23% of those diagnosed were not consulted for the patient,
      including two malign tumours. CONCLUSIONS: skin disease has a relevant place in
      primary health care clinics; the dermatological training of the primary health
      care doctor should be aimed at the most frequent diagnoses in his setting; active
      detection of skin lesions is very important.

PMID- 1366212
TI  - [Current changes in the predominant mechanisms of the transmission of brucellosis
      in the province of Valencia].
AB  - A descriptive epidemiological study of brucellosis in the province of Valencia
      was carried out over the period 1985-1988. In this report predominant
      transmission mechanisms and their relation with sex, age and profession variables
      are described. Moreover, the results obtained were compared with those from other
      brucellosis epidemiologies which were previously carried out in the province of
      Valencia. It can be seen that there is a relative increase in the direct
      contagion mechanism and a decrease in the indirect contagion mechanism with
      respect to the previous periods, which has effects on the variations of sex and
      profession distribution of the disease. The changes observed could be attributed
      to a better sanitary control of milk and diary products, mainly fresh cheese,
      which are very important in the transmission of the disease in the province of
      Valencia.

PMID- 1366211
TI  - [The seroprevalence of human toxoplasmosis in Cordoba].
AB  - A seroprevalency study of human toxoplasmosis was carried out in Cordoba, using
      indirect immunofluorescence and indirect hemagglutination. The sample of people
      interviewed was made up of 443 serums, 356 supposedly healthy people (mainly
      students) and 87, considered "high risk" (patients from the "Reina Sofia"
      Hospital). The positiveness obtained for the total of the sample was 43.79% with
      IFI and 53.59% for HAI. As regards sex of the person tested, prevalence is higher
      in women, with 54.36% and 70.47% with IFI and HAI respectively, in men the scores
      were 38.43% and 44.90% for the same tests. As far as the origin of the sample was
      concerned, there were 31.18% with IFI and 43.25% for HAI of the normal
      population, in the "high risk" sample, for both tests it was 95.40%. With both
      tests there are significative differences in low amounts, but not in high
      dilutions. We conclude that human toxoplasmosis is present and widespread in the
      studied population.

PMID- 1366213
TI  - [Information in general medicine].

PMID- 1366214
TI  - [The applications to chronicity in mental health of the International
      Classification of Impairments, Disabilities and Handicaps].
AB  - The present work focuses on the difficulties to accomplish an adequate valuation
      of needs in "chronic" psychical patients. First, a reference is made to the
      characteristics of the so-called "new chronics", mostly cared outside the
      hospital, after the process of deinstitutionalization carried out during the last
      years. Then, an analysis of the International Classification of Deficiencies,
      Discapacities and Invalidities published by the World Health Organization in
      1980, (as annex of the International Classification of Diseases) is carried out.
      This work studies basically the description of its classification contents and a
      valuation of its effectiveness as and instrument to be used in the planning and
      evaluation works and in the care of patients with mental "chronic" diseases.

PMID- 1366215
TI  - [The potability of the water in a region with a high level of natural radiation].
AB  - BACKGROUND: The recent Spanish legislation on drinkable waters for public use
      includes a paragraph establishing the requirements to be fulfilled by waters in
      relation with their radioactivity and the methods to be used to measure it. As
      water radioactivity depends on the radioactive content of the grounds and rocks
      where it flows, it is possible to expect high levels in those zones whose
      characteristic is their high level of natural radiation. METHODS: For this
      reason, we have organized two measurement campaigns with the objective of
      characterizing the drinkable waters in an Spanish area, where the radioactive
      elements concentration in the ground is high. The methodology used is as
      described in legislation, using a low-bottomed proportional counter. RESULTS: The
      results we have obtained indicate that the zone, where measurements have been
      made, shows lower radioactivity levels than the legally established limits,
      nevertheless, at same time, there appear several points, where the radioactivity
      levels are high, showing values exceeding in great measure the legal limit for
      drinkable waters. CONCLUSIONS: With the results, we have obtained, its seems
      necessary that a greater attention is paid to drinkable waters in those points,
      where the radioactivity levels are high including corrective measures.

PMID- 1366216
TI  - [The validation of the process and the results of an information system in
      primary care].
AB  - BACKGROUND: The needs of information for the primary health care centers planning
      and management, and the poor situation we started from, have generated a large
      amount of information systems, which, as a general rule, have not been
      sufficiently evaluated. Since 1986, in the Area de Gestion, 7, Centro, of the ICS
      here exists an information system of the general medicine services with a
      sampling method (ANAC-2). The validation of some aspects of the process and
      content is shown in order to evaluate the quality of information. METHODS: The
      problems arisen during the process of collecting data from nine centers are
      analyzed during six months and its information content is compared with the one
      of each system with a standard respect their value. To evaluate the concordance,
      we have used a graphic representation of the differences of each system with a
      standard respect their mean value, and the "limits of agreement". RESULTS: On
      relation with the problems of collecting data, two centers show a nonfulfillment
      of the observation calendar higher than 20% and the logical divergences are not
      important. The kind of visits distribution is quite correct, even if the estimate
      of the whole number of visits is higher than 20% in two centers. In the activity
      indicators, the system of reference has a tendency to give average values lower
      than the ANAC-2, with the exception of prescription/visit. In referrals and
      prescriptions, the use of different sources of information between systems
      produces an average difference of 3.3 interconsults/100 visits and 0.8
      prescriptions/visit respectively. Generally, the limits of agreement are wide and
      become unacceptable in laboratory. CONCLUSIONS: The study carried out is
      evaluated positively, for it detects the problematical areas which can be
      modified or require further studies. The importance of validating the information
      systems is emphasized, in spite of difficulties.

PMID- 1366217
TI  - [Searching for the utility of an information system in primary care in Castilla
      and Leon].
AB  - BACKGROUND: In Castille-Leon, there is an information system in primary health
      care. The target is to describe several operativity indicators in a primary
      health care center with the date collected with this system and indirectly, to
      initiate its evaluation. METHODS: The study was carried out in an urban primary
      health care center in Valladolid. A descriptive analysis of the data, related to
      the health problems demanded in 1990, collected in first sampling during a week
      of every month, is carried out. RESULTS: The global work load was 30-2 problems
      demanded to the doctor per day. The 5.7% of consult were home visits, and the
      prevailing problems were circulatory and respiratory. Per 100 problems, 10
      laboratory test, 4.4 radiographies, 1.4 electrocardiograms and 5.25 other
      different tests were required. No adequate nor periodical informations was
      received from the administration to which data were sent. CONCLUSIONS:
      Insufficiency in the system to characterize in an adequate way, the health care
      activities complexity and lack of use of the provided data and of analysis.

PMID- 1366218
TI  - [A survey on the satisfaction of the users of the Zaidin-Sur de Granada Health
      Center (1989)].
AB  - In order to know the users's degree of satisfaction in the Primary Health Care
      Center of Zaidin-Sur in Granada, a survey has been carried out by means of a
      personal interview at home in an aleatory sample of 615 individuals. The
      questionnaire has 28 closed questions with multiple answer and collects
      sociodemographic variables, self-perception of health condition, acceptability of
      medical and nursery care. The interview was anonymous and carried out by nursery
      students of third year. The 52% of the sample expressed that his health level was
      "excellent" or "good" and it was worse when the educational level was lower and
      the age was higher. The group of workers showed the highest valuation of health
      condition. The levels of trust on the doctor, the time of dedication and the
      information given to the patient reach slightly lower values than the ones found
      in literature; personal treatment and interest towards the patient have been
      valued the best. Center space structure and timetable have been the most
      penalized variables. We conclude that there is a need of improving the nursery
      service care a need of the information, from all the professionals working in the
      center, given to the patients on their problems, which are the cause of their
      going to the health consult, and the need of enlarging the space of the center.

PMID- 1366219
TI  - [Hepatitis C viral infection and the consumption of intravenous drugs].
AB  - BACKGROUND: To know the antibodies seroprevalence against hepatitis C virus
      (HCV), as well as other factors associated to these antibodies presence in a
      group of intravenous drug users (IVDU) in Baleares. To know what screening test
      would be the most adequate to detect antibodies against HCV in this group.
      METHODS: The presence of HCV antibodies in serum was determined in 110 IVDU
      patients, admitted to hospital during 1990 in a unit of opium detoxifying, by
      techniques enzyme immunotesting (ELISA) and immunoblotting (RIBA); the drug abuse
      history as well as serologies against human immunodeficiency virus (HIV),
      hepatitis B (HBV) and syphilis. RESULTS: The seroprevalence found by techniques
      ELISA is 71% and 95% respectively for the tests of first and second generation;
      using the method RIBA the seroprevalence is 86%. The HIV seroprevalence was 36%
      and a 53% were anti-HBs positive. No significative differences were found between
      the positive and negative anti HCV in relation with drug use variables: as first
      year of consumption and time of addiction, nor with the presence of HIV and HBV
      markers. CONCLUSIONS: The HCV seroprevalence among IVDU of the sample studied is
      similar to those described for this risk group by other authors in other zones.
      Such infection is not statistically associated with other variables of the drug
      abuse history nor with the infection by HBV and HIV. Despite the discordances of
      the HCV seroprevalence with the three test used in the study, the technique ELISA
      of second generation could be the ideal method of screening of antibodies against
      the HCV in this risk group.

PMID- 1366221
TI  - [Epidemiology in scientific thought].

PMID- 1366220
TI  - [The evaluation of the effects of ambient noise on the residents of the historic
      center of Valencia].
AB  - BACKGROUND: The acoustic contamination in residential areas is a generalized
      problem to solve it, it is necessary to have an available precise information
      about its magnitude and effects upon the population. METHODS: We show the first
      results of a study on the acoustic contamination in the historical center of
      Valencia and about its effects upon that district residents. A noise map has been
      made measuring the daily sound level in 135 points regularly distributed. At the
      same time, 418 telephone polls among the residents in that district has been
      carried out. RESULTS: The noise levels, existing in the studied zone, are very
      high, it has been obtained an average equivalent sound level (Leq) of 71.6
      decibels A (dBA). About a 60% of the surveyed persons declare to be "troubled",
      because of the noise and one out of four surveyed persons find it difficult to
      get to sleep for the same reason. Road traffic is the main source of trouble.
      There has been observed a relation between certain personal characteristics in
      the surveyed persons and the answers obtained, although it does not reach an
      statistical significance. CONCLUSIONS: In the historical center of Valencia,
      there exists an important problem of environmental noise and the daily levels
      exceed clearly the recommended limits. It seems that traffic is the main source
      of noise probably combined with a deficient urban structure which does not allow
      a fluid vehicular traffic. The residents in this zone are aware of the problem
      and a great proportion of them declare to be damaged in a greater or smaller
      magnitude. Although the sensitivity to noise could be in relation with certain
      personal factors in the surveyed persons.

PMID- 1366222
TI  - [The cholesterol contained in low-density lipoproteins or apolipoprotein B in the
      prediction of cardiovascular risk?].

PMID- 1366223
TI  - [Waste water management in a health area: environmental hygiene in primary care].
AB  - BACKGROUND: Within the scope of the programmes to be developed by the primary
      health care parties, we consider it interesting to investigate the sewage
      management in our health area because of its impact on the population health and
      welfare and the main socioeconomic local activities: agriculture and tourism.
      METHOD: We carry out an epidemiological descriptive study: we review the most
      important structural and functional characteristics of the sewage depuration and
      collection in the municipality of S. Javier (Murcia). RESULTS: The evaluation of
      the collected data made it obvious that deficiencies exist in the collection
      system as well as in the sewage processing; both deficiencies were shown in some
      places of the locality and in particular periods of the year, with a consequent
      risk of environmental contamination and enteric diseases transmission among
      population and summer holidaymakers. CONCLUSIONS: A positive corrective action on
      the installations by the organisms responsible for the local sanitation as a
      response to these conclusions, which we informed due time, constitutes a good
      stimulant to go on investigating this question of such a great sanitary and
      general interest, which is almost unknown in medical literature.

PMID- 1366224
TI  - [The spread of human immunodeficiency virus infection (HIV-1/HIV-2) and of
      hepatitis B and C in non-drug-addicted prostitutes. Extremadura].
AB  - BACKGROUND: The proportion of cases of AIDS in Extremadura, in which sexual
      transmission has existed, is comparatively lower than the national one. The
      possibilities of the infection introduction in the general population may
      increase the relative importance of this way of transmission in the future.
      Penetration of HIV is unknown in prostitutes living and working in the Autonomous
      Community of Extremadura, as a collective associated to virus sexual transmission
      and to other socio-cultural risk factors involved. METHODS: Women exercising
      prostitution are established as "target" population; the existence of intravenous
      drug addiction in the last 5 years is the criterion for exclusion, the sample
      comes from 11 nodal populations of Extremadura, and is constituted by 95 persons,
      selected in their own working places and having previously obtained their
      informed consent. The city American bar, 37.9%, the prostitution house 32.6%, and
      the road American bar are the most frequent kinds of prostitution. Besides the
      socio-sanitary poll, infections by HIV-1, HIV-2, Hepatitis B,C, virus, associated
      to certain risk practices are investigated. RESULTS: The prevalence of infection
      by HIV-1 is 1.05% with confidence intervals of 0 and 3%; no seropositivity to HIV
      2 was detected. In forty-two out of the women surveyed, 44, 21% show some
      positive marker of the hepatitis-B (HBV) (C.I. 95% 34.1-54.2). Antibodies to the
      Hepatitis C virus (Anti-HCV) are present in three women, 3.16% (C.I. 95% 0-6%).
      Among the risk practices studied, it stands out that 44% use condoms in their
      relations with clients and only in 2.54% because of clients demand. In
      unremunerated couples, between 50 and 70% never use preservatives in sexual
      relations. CONCLUSIONS: These results suggest that infections by HIV-1/HIV-2 are
      not prevalent in non drug-users prostitutes in Extremadura. Likewise, the low use
      of preservative, in professional relations as well as in couples, is
      significative; and it stands out the high frequency of refusal to use
      preservatives by clients or partners. It is considered necessary to increase
      health education of these collectives and general heterosexual population, in
      order to change attitudes in private or professional sexual relations.

PMID- 1366225
TI  - [An epidemiological study of congenital dyschromatopsias in schoolchildren].
AB  - BACKGROUND: Taking into consideration that present-day communication is based on
      colours and shapes, the prevalence of anomalies in the chromatic sight in the red
      green axis has been studied in the school boys of the city of Albacete. METHODS:
      The test of Ishihara has been used in an aleatory representative sample; and
      dyschromatopsic pupils, so classified in this test, have been further explored
      with the anomaloscopy Pickford-Nicolson, in order to know their anomaly kind and
      degree. RESULTS: The prevalence obtained is similar to those reported by other
      studies carried out in the European white race. CONCLUSIONS: Taking into account
      the transcendence of this phenomenon, we consider that this exploration must be
      included in the systematic examinations at school labour and general level.

PMID- 1366226
TI  - [A microbiological and physicochemical analysis of the water in swimming pools on
      the island of Tenerife].
AB  - BACKGROUND: A microbiological and physiochemical analysis has been made from 60
      samples of water from two swimming pools in Santa Cruz de Tenerife in order to
      know the hygienic condition and to establish the most adequate microbiological
      indicators. The water of the two swimming pools has a different origin: sea water
      (Swimming pool B) and public supply (Swimming pool A), and so, different
      processings are used. METHODS: The analytical methodology was based on the
      Spanish current day regulations for the control of drinkable waters for public
      use, as well as on the methods the American Public Health Association recommends.
      RESULTS: There have been found differences between one swimming pool and the
      other, depending basically on the water characteristics and the processings used
      to treat it; there exists a greater microbiological contamination in the samples
      from the swimming pool B. It has been proved that medium R2A is better than
      medium P.C.A. to recount total mesophilic aerobes in both swimming pools.
      CONCLUSIONS: The isolation of St. aureus species in samples from the swimming
      pool B makes of it a possible microbiological indicator for the hygienic control
      of swimming pool waters of marine origin. Likewise, the presence of mycobacterium
      species in samples of the swimming pool A confirms its resistance to
      concentrations of growth inhibitors of free chlorine.

PMID- 1366228
TI  - [The tobacco habit among fishermen of the Barbate coast (Cadiz)].
AB  - BACKGROUND: Nowadays, in scientific spheres, it is unquestionable that tobacco
      damages health. We study the introduction of tobacco habit among inshore
      fishermen of Barbate (Cadiz), for we consider that this is a highly receptive
      population to tobacco use because of hard work and its low socio-cultural level.
      METHODS: A transversal descriptive study is carried out in order to determine the
      prevalence of tobacco use in this population. With this purpose, a questionnaire
      of 26 variables (epidemiological, sociodemographic and related to tobacco use)
      has been elaborated; 207 fishermen, equal to 10.35% of the whole inshore fishing
      fleet of Barbate, have been surveyed. RESULTS: The mean age of the sample is 39.9
      years, with distribution per age groups from 16 to 65 years. The result of the
      survey carried out is an smoker percentage of 81.15% among the fishermen of the
      inshore fishing fleet of Barbate. CONCLUSIONS: It is obvious that this population
      has an important deeply rooted tobacco habit. Anyway, our results are similar to
      those obtained by other Spanish authors when they study tobacco habit in
      fishermen.

PMID- 1366227
TI  - [The prevalence of enteropathogens in urban day nurseries].
AB  - BACKGROUND: Survey on the intestinal pathogens prevalence in a population of
      preschool children attending to the urban day-nurseries. METHODS: Samples of
      faeces of 408 children and 31 adults, in their charge, were collected. The
      children were classified per sex, age and kind of day-nursery they were to; data
      on their physical condition and the faeces characteristics were obtained.
      RESULTS: Parasites were the enteropathogens, found with the greatest frequency
      (21% of children and 19% of adults), next were rotavirus (3% of the children's
      samples and only one case in adults). The cases of a double parasitization only
      were 0.74% of the total number of the children surveyed (3 children per each
      case). CONCLUSIONS: The highest prevalence of enteropathogens in children
      attending to the urban day-nurseries in our community belongs to the group of
      parasites; rotavirus are a much smaller group and bacterium are only isolated
      cases.

PMID- 1366229
TI  - [Environmental sanitation and typhoid-paratyphoid infection morbidity in
      Valencia].
AB  - BACKGROUND: We intend to study the evolution of morbidity by typhoid-paratyphoid
      infections (TPI) in Spain and Valencia (1940-1990) as well as TPI morbidity and
      degree of sanitation in Valencia. METHODS: Data related to morbidity, as well as
      the sanitation basic data in Valencia, have been obtained from official sources.
      Morbidity rates belonging to Spain and Valencia have been calculated. RESULTS: It
      is found a decreasing trend of morbidity in Spain and Valencia. By Health Areas,
      a great decrease stands out in Valencia-City and, as a general rule, the highest
      rates belonged to the lowest automatic chlorination percentages. In general,
      there is an improvement in chlorination, sewers and sewage-depuration equipment.
      CONCLUSIONS: TPI morbidity in Spain shows a decreasing trend in both cases; it is
      more evident in Valencia when establishing a relation of TPI morbidity with the
      degree of hygiene by Health Areas of Valencia, an inverse relation appears and
      the highest rates belong to the interior Areas. The conclusion is that there is a
      remarkable improvement in the hygiene general situation in Valencia; in the city
      as well as in all the Health Areas.

PMID- 1366230
TI  - [The prevalence of headaches in a university population].
AB  - BACKGROUND: We have been interested in the prevalence of cephalalgias in a
      population of university students, as well as its intensity, frequency and
      duration parameters. METHODS: A group of 490 adult persons, students in the
      university of Murcia, was put to a questionnaire prepared for this purpose in
      which they were asked about the presence or absence of cephalalgia episodes
      during the last 12 months, as well as about their intensity, frequency and
      duration. They were also asked whether they knew about their headache cause or
      diagnosis. RESULTS: Results show a characteristic profile 91.9% of persons
      declare to have suffered from migraines during the last year. Out of them, 40.5%
      with a minimum frequency of one episode per week with a perceived intermediate
      intensity of (43.2%) and a duration of 1 to 4 hours (59.7%). Furthermore,
      statistically significant differences were found in relation with sex: women
      suffered from more frequent lasting migraines than men; on the contrary, no
      differences were found between sexes in relation with headache intensity. It is
      also noticed that 89.65% of persons do not know about the diagnosis or etiology
      of his trouble. CONCLUSIONS: Data make evident the high prevalence of headache in
      University students; This justifies, in our opinion, the implementation of
      programmes of evaluation dealing with this problem in University students
      populations.

PMID- 1366231
TI  - Stability and reconstitution of D-glyceraldehyde-3-phosphate dehydrogenase from
      the hyperthermophilic eubacterium Thermotoga maritima.
AB  - The molecular basis of thermal stability of globular proteins is a highly
      significant yet unsolved problem. The most promising approach to its solution is
      the investigation of the structure-function relationship of homologous enzymes
      from mesophilic and thermophilic sources. In this context, D-glyceraldehyde-3
      phosphate dehydrogenase has been the most extensively studied model system. In
      the present study, the most thermostable homolog isolated so far is described
      with special emphasis on the stability of the enzyme under varying solvent
      conditions. D-Glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic
      eubacterium Thermotoga maritima is an intrinsically thermostable enzyme with a
      thermal transition temperature around 110 degrees C. The amino acid sequence,
      electrophoresis, and sedimentation analysis prove the enzyme to be a homotetramer
      with a gross structure similar to its mesophilic counterparts. The enzyme in the
      absence and in the presence of its coenzyme, NAD+, exhibits no drastic structural
      differences except for a 3% change in sedimentation velocity reflecting slight
      alterations in the quaternary structure of the enzyme. At low temperature, in the
      absence of denaturants, neither "cold denaturation" nor subunit dissociation are
      detectable. Guanidinium chloride and pH-dependent deactivation precede the
      decrease in fluorescence emission and ellipticity, suggesting a complex
      denaturation mechanism. An up to 3-fold activation of the enzyme at low
      guanidinium concentration may be interpreted in terms of a compensation of the
      tight packing of the thermophilic enzyme at low temperature. Under destabilizing
      conditions, e.g. moderate concentrations of chaotropic agents, low temperature
      favors denaturation. The effect becomes important in reconstitution experiments
      after preceding guanidinium denaturation; the reactivation yield at low
      temperature drops to zero, whereas between 35 and 80 degrees C reactivation
      exceeds 80%. Shifting the temperature from approximately 0 degrees C to greater
      than or equal to 30 degrees C releases a trapped tetrameric intermediate in a
      fast reaction. Concentration-dependent reactivation experiments prove
      renaturation of the enzyme to involve consecutive folding and association steps.
      Reconstitution at room temperature yields the native protein, in spite of the
      fact that the temperature of the processes in vitro and in vivo differ by more
      than 60 degrees C.

PMID- 1366232
TI  - [Cardiovascular profile of the ACE-inhibitor Quinapril. Worshop report. Freiburg
      in Breisgau, 15-16 May 1992].

PMID- 1366233
TI  - [ACE-inhibitor therapy after infarction overcomes asymptomatic cardiac
      insufficiency].

PMID- 1366234
TI  - [Chronic inflammatory bowel diseases. Thinking of it early enough!].

PMID- 1366235
TI  - Lowering the morbidity and mortality from trauma.

PMID- 1366236
TI  - Successful treatment of focal hepatic candidiasis with liposomal amphotericin B.

PMID- 1366237
TI  - Short-term strenuous exercise training: effects on blood pressure and hormonal
      levels in mild hypertension.
AB  - The effect of a six-week strenuous exercise training programme (modified Bruce
      protocol, treadmill, three times per week) on resting and exercising blood
      pressure, heart rate, plasma catecholamines, chromogranin A, renin activity and
      aldosterone levels was investigated in 15 patients with mild hypertension. An
      identical exercise test was conducted at baseline and study close (six weeks). At
      follow-up, seven to ten days after study close, patients completed an exercise
      test of equivalent intensity to that at baseline, achieving comparable heart rate
      levels at maximal exercise. On each occasion, blood pressure, heart rate and
      hormonal variables were measured at rest (supine), maximal exercise and ten
      minutes after stopping exercise. Resting and exercising blood pressure and heart
      rate were reduced by the six-week exercise regimen. There was a trend, although
      not statistically significant, for resting plasma noradrenaline levels to be
      lower at study close. The reduction in blood pressure and heart rate at maximal
      exercise was associated with a significant attenuation of the plasma renin
      response to exercise. Plasma catecholamines also appeared to be lower after
      exercise training, although this effect was not statistically significant. Plasma
      levels of chromogranin A and aldosterone measured at rest and maximal exercise
      were not influenced by the exercise regimen. Further controlled studies are
      required to corroborate the results of this preliminary study.

PMID- 1366239
TI  - Spinal epidermoid cyst and cauda equina syndrome in a teenage girl.
AB  - A sixteen year old girl presented with a four year history of hip pain followed
      subsequently by back pain radiating down her left leg, progressive urgency of
      micturition, urinary incontinence, a feeling of bladder fullness and incomplete
      bladder emptying, faecal impaction and finally, numbness in both of her buttocks.
      A diagnosis of Cauda Equina Syndrome was suspected on the history and the
      clinical examination. A plain X-ray of her lumbar spine revealed evidence of a
      slow growing mass within the vertebral canal at the level of L3. A Magnetic
      Resonance Imaging (MRI) scan confirmed an intradural space occupying lesion at
      the same level. This lesion was surgically removed and histological examination
      revealed a benign epidermoid cyst.

PMID- 1366240
TI  - Hepatic haemangiosarcoma in a patient with psoriasis and Crohn's disease.
AB  - Hepatic haemangiosarcoma is a rare condition although there are known carcinogens
      in 25%. This case reports hepatic haemangiosarcoma in a 59 year old man with
      psoriasis and Crohn's disease who had previously received combined treatment with
      psoralen and UVA light.

PMID- 1366241
TI  - Cheilectomy for hallux rigidus.
AB  - Cheilectomy is the excision of an irregular osseous rim that interferes with
      joint motion. Twenty cases of hallux rigidus/limitus treated by cheilectomy have
      been reviewed 18 months after surgery. A satisfactory outcome was achieved in all
      but 2 cases, which were failures. Range of joint motion, in particular dorsi
      flexion, improved in all but 6 cases. Cheilectomy is a simple and effective
      alternative to arthrodesis in the treatment of hallux rigidus.

PMID- 1366238
TI  - Boerhaave's syndrome as a complication of pre-existent gastrointestinal disease.
AB  - Two cases of Boerhaave's Syndrome complicating vomiting of gastrointestinal
      obstruction are described. The successful management of each case is recounted
      and certain pitfalls noted. This association has received scant attention in the
      extensive literature on Boerhaave's Syndrome. We were not able to find a previous
      report of successful management of this dual pathology. Nevertheless, the
      location of two such cases at a District General Hospital within a decade
      suggests that it may not be exceptionally rare. We review the literature
      pertaining to the association of Boerhaave's Syndrome with pre-existent
      gastrointestinal disease. The suggestion is made that the possibility of a second
      surgical condition should be borne in mind when treating patients with this
      syndrome. We stress that the presence of symptoms due to pre-existent upper
      gastrointestinal disease may contribute to diagnostic delay in the recognition of
      Boerhaave's Syndrome.

PMID- 1366242
TI  - TSH as an index of L-thyroxine replacement and suppression therapy.
AB  - When hypothalamic-pituitary function is normal, serum TSH levels measured by
      ultrasensitive assay yield bioassays of endogenous thyroid action and thus
      provide an ideal index of thyroid secretion and its relationship to fluctuating
      endogenous thyroid levels. It is theoretically possible that patients receiving
      exogenous L-thyroxine for primary hypothyroidism should have suppressed TSH
      levels if physiological needs are constantly met. To examine this possibility
      free thyroxine, FT4 and TSH were measured in 90 clinically euthyroid patients
      receiving treatment with L-thyroxine for primary hypothyroidism. TSH levels were
      normal in 44, suppressed in 16 and elevated in 30 patients. FT4 levels were
      normal in 68, elevated in 13 and suppressed in 9 patients. Normal TSH levels were
      associated with normal FT4 levels in 79.5% of patients, elevated FT4 levels in
      13.6% and low FT4 in 6.8%. Suppressed TSH levels were associated with elevated
      FT4 levels in 37.5% of patients and normal FT4 levels in 62.5%. When FT4 levels
      were normal, however, TSH levels were normal in only 51.5% and abnormal in 48.5%.
      We also examined the possibility that FT4 levels may remain within normal range
      when TSH is suppressed during L-thyroxine treatment for goitre or cancer. FT4 and
      TSH were measured in 45 patients on L-thyroxine as TSH suppression treatment. TSH
      was suppressed in 23 patients (51.1%), normal in 20 (44.4%) and elevated in 2
      (4.5%). When TSH was suppressed, FT4 was elevated in 30.4% but normal in 69.6% of
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1366243
TI  - [Clinical epidemiology versus public health epidemiology].

PMID- 1366244
TI  - [Screening methods in mental disorders of children and adolescents in primary
      health care].
AB  - A revision of the principal studies of prevalence of mental disorders in
      childhood is made. We present a bibliographic research about screening
      instruments for mental disorders in children and adolescents comparing the child
      behaviour scales checklists most usually employed in epidemiological surveys.

PMID- 1366246
TI  - [Smoking in a mining enterprise in Asturias: habits and knowledge].
AB  - Tobacco is the first avoidable cause of mortality and morbidity in the developed
      countries. A survey on the tobacco habit was carried out in a mining firm of 1420
      workmen. The target was to quantify the severity of this problem, to carry out an
      information campaign and to provide help with nicotine chewing gam and
      psychological support. A 63% were usual smokers; a 20.1% were nonsmokers; and a
      16.8% were former smokers. The group of smokers had a smaller knowledge on the
      risks of tobacco than the other two groups. Only a 1% of smokers went to the
      audio-visual information meetings in their respective localities and to the
      antismoking consulting of our hospital. An informative programme on "Tobacco and
      Health" was sent to all them.

PMID- 1366245
TI  - [Promotion of infant health. Experiences in a rural health center].
AB  - BACKGROUND: The evaluation of the feeding changes in the first months of life is
      used to estimate the achievement of more healthy practices, after a year of
      developing the infant health surveillance programme. METHODS: A retrospective
      study was carried out in a unit of Pediatrics of a Primary Health Center.... The
      clinical histories of children, born between 1-4-90 and 30-9-90 (group I, n = 55)
      and those of the children born between 1-4-89 and 30-9-89 (group II, n = 41) were
      reviewed. The evaluation ended the 30-3-91. Neonatal hospital morbidity, socio
      familiar data, and the feeding practices during the first six months of life were
      studied. RESULTS: The mothers, who were 20 years or less at delivery, were 12 in
      the group I, and 2 in the group II. The proportion of housekeepers was near the
      70% in both groups. Breast-feeding during the first month of life is 85,45% in
      group I and 53,66% in group II (p < 0.001). CONCLUSIONS: Increase of adolescent
      mothers and SO, higher number of children with possible psycho-social and health
      risks. Suitable social conditions for maternal participation in the activities of
      the Infant Health surveillance Programme. Health education is the most adequate
      method to establish a more healthy relation between mother and child.

PMID- 1366247
TI  - [Evaluation of a project of primary prevention of smoking: the Barcelona PASE
      project].
AB  - The results of the short-term evaluation of a program to prevent the use of
      tobacco and other substances among schoolchildren of sixth and seventh grade are
      presented. Schoolchildren who participated in the project show significant
      differences when compared to a reference group through a matched analysis in the
      regular use of tobacco and having bought tobacco, but not in the experimentation
      nor in the intention to smoke. The results suggest the program is useful to
      prevent the onset of smoking, although longer term evaluation data are needed.
      The results and their implications for a comprehensive smoking prevention
      approach in schools are discussed.

PMID- 1366248
TI  - [Immunogenicity of the vaccine against hepatitis B virus in schoolchildren of
      Madrid].
AB  - We carried out a vaccine program against Hepatitis B in scholar population aged 5
      to 17 educated in 3 institutions of Madrid city/ region. Those children who
      followed the vaccination criteria (negative HBsAg and Anti HBc markers) were
      vaccinated. The vaccination regimen (Engerix B recombinant DNA vaccine) was 0-1-6
      months and dose was 10 and 20 ug i.m. for those aged 6 to 13 and 13 to 17
      respectively. The postvaccine serologic results (anti-HBs titer) was evaluated
      one month after tha last dose, at 7th month from the beginning. The variables of
      study were age and sex for each individual. Corresponding to these variables both
      seroconversion rate (percentage of patients with 10 Ul/l of-anti-HBs) and the
      geometric mean titer of antibodies (GMT anti-HBs titer) were determined. The
      overall seroconversion rate at 7th month was 99%. There is not significant
      association neither regarding the sex nor mean age between "responders" and "no
      responders". The titer of anti-HBs antibodies, expressed using the G.M.T., which
      was reached at 7th month was 9.283.2 UI/I. Finally, there is not correlation
      between age and anti-HBs antibody titer.

PMID- 1366249
TI  - [Evolution of adolescent fertility and its association with evolution of income
      in the Spanish provinces during the period 1975-1985].
AB  - BACKGROUND: Fertility rates in women under 21, during the period 1975-1985 in
      Spain, have analyzed, as well as their association with the evolution of the
      socioeconomic indicators in order to study the distribution and associated
      factors to adolescent maternity in our environment. METHODS: The fertility rates
      have been elaborated from the Official Demographic Statistics. The socioeconomic
      indicators have been obtained from the Statistics Year Book of the National
      Institute of Statistics and from other complementary sources. The method of
      weighted linear regression has been used to analyze the association between the
      indicators and the rates at the provincial level. RESULTS: The fertility rates
      have decreased a 16% in mothers from 15 to 19 years old in Spain, between 1975
      and 1985. The highest accumulated rates belong to the Communities of Canarias
      (42.8 births by 1000 women of 15 to 19, Galicia (38.1) Murcia (33.7) and
      Andalucia (30.3). In the regression analysis, the income evolution shows an
      association with the fertility evolution in the group from 15 to 19 years old,
      and this association remains when we take into account unemployment, index of
      provincial development and birth rate, which allows to explain a 49% of the
      variance. Fertility of adolescent under 15 is only associated with the income
      evolution, with a determination coefficient of 0.29. CONCLUSIONS: Results
      indicate that early maternity has decreased in Spain, although there are
      geographical differences, which cam, in some measure, be related with social
      economic factors.

PMID- 1366251
TI  - [With responsiveness to the incorporation of marketing into the health services].

PMID- 1366250
TI  - [Measles outbreak in Tormaleo (Asturias)].
AB  - BACKGROUND: We have studied a measles outbreak in the town of Tormaleo. The
      number of cases went beyond all the expectations and tendencies of the disease in
      the area. As a great proportion of the cases were older children, we thought it
      appropriate to inquire into it, as well as to evaluate the vaccine effectiveness.
      METHODS: The research was carried out retrospectively, at the end of the
      epidemic, in a cohort retrospective study. The children who had not suffered the
      disease or had not been vaccinated were considered as the group at risk, with no
      immunological protection, and the vaccinated ones as the protected immunized
      group. It is assumed that practically the whole collectivity gets into contact
      with the virus in a measles epidemic. The affected population consisted of 92
      children: 41 males and 51 females. A total sum of 36 cases of measles was
      clinically diagnosed: 13 boys and 23 girls. RESULTS: The highest incidence came
      from the age group of 12, 13 and 14 years old. The different measures of
      frequency, epidemiological risk parameters and global effectiveness of the
      vaccine were calculated. The incidence, among the nonvaccinated ones, was 84%,
      and 15% among the vaccinated ones with a global effectiveness of the vaccine of
      82%. CONCLUSIONS: The effectiveness of the vaccine is similar to the one found in
      other studies. The risk of suffering. The disease for non-vaccinated people is
      extremely high.

PMID- 1366252
TI  - AIDS surveillance in Canada.

PMID- 1366253
TI  - Worldwide influenza activity.

PMID- 1366254
TI  - Hospital outbreak of Salmonella enteriditis infection--Ontario.

PMID- 1366255
TI  - Seat belts in pregnancy.

PMID- 1366257
TI  - Comparison between enalapril and lisinopril in mild-moderate hypertension: a
      comprehensive model for evaluation of drug efficacy.
AB  - The objective of this study was to compare enalapril with lisinopril in terms of
      blood pressure control at rest, during dynamic exercise test, during isometric
      exercise test, and during 24 h--with special focus on blood pressure control
      during the morning hours, 18-24 h post-dose. Furthermore, we compared ACE
      activity in serum before and after 4 weeks of drug treatment. A four-week double
      blind, randomized parallel group study compared enalapril 20 mg o.d. with
      lisinopril 20 mg o.d. preceded by a 4-week single blind run-in period on placebo.
      Fifty-eight patients (49 males and 9 females, mean age 50.9) were recruited and
      56 completed the study. Blood pressures at randomization were 161/108 and 164/106
      for the enalapril and the lisinopril subjects, respectively. Echo: LVPWd 9.5
      (normal range 6-12 mm) and IVSd 10.3 mm (normal range 6-12 mm). STATISTICS:
      ANCOVA. Enalapril and lisinopril were equally effective in lowering blood
      pressure at rest, during dynamic and isometric exercise as well as during 24 h.
      The attained blood pressure levels during the early morning hours were for
      enalapril treatment 119/76 and 121/76 mmHg for lisinopril treatment. The ACE
      activity in serum 24 h post-dose was lower (p < 0.001) after treatment with
      lisinopril 8.0 (SD 3.3) mumol/min/1 than with enalapril 16.1 (SD 6.0). The
      corresponding values for placebo were 18.8 (SD 4.6) and 17.8 (SD 5.7). No
      difference was found in blood pressure lowering efficacy between enalapril and
      lisinopril even though the blood pressure changes were evaluated in a more
      comprehensive way than in earlier studies of these drugs.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1366256
TI  - [Implementing secondary poliomyelitis vaccination].
AB  - Revaccination is necessary also in poliomyelitis immunisation. Recommendations
      concerning type and frequency of vaccination vary. According to the results of an
      investigation in vaccinating patients 10-20 years after the last oral vaccination
      life vaccine can be administered for revaccination. After more than 20 years
      patients are seronegative. Therefore, a new basal immunisation is necessary after
      prevaccination with inactivated vaccine.

PMID- 1366258
TI  - Inhibition of endothelin (ET-1) induced pressor responses by the endothelin (ETA)
      receptor antagonist FR139317 in the pithed rat.
AB  - The effects of the novel ETA receptor antagonist, FR 139317, on ET-1 induced
      blood pressure changes were studied in the pithed Sprague-Dawley rat. FR139317 in
      a dose of 0.025 mg/kg b.w. had no effect while 0.05-1 mg/kg b.w. dose dependently
      inhibited the pressor response to an i.v. bolus injection of ET6-1 (800
      pmoles/kg). While FR139317 potently inhibited the magnitide and duration of the
      ET-1 induced pressor response, the ETA antagonist did not significantly influence
      the shortlasting initial depressor response. We conclude that FR139317 in the
      pithed rat potently inhibits ET-1 mediated pressor responses and that this agent
      may become a significant tool to elucidate the putative physiological and
      pathophysiological role of ETA receptor mediated responses.

PMID- 1366259
TI  - Prospective randomized open blinded end-point (PROBE) study. A novel design for
      intervention trials. Prospective Randomized Open Blinded End-Point.
AB  - A novel design for intervention studies is presented, the so called PROBE study
      (Prospective Randomized Open, Blinded End-point). This design is compared to the
      classical double-blind design. Among the advantages of the PROBE design are lower
      cost and greater similarity to standard clinical practice, which should make the
      results more easily applicable in routine medical care. Since end-points are
      evaluated by a blinded end-point committee it is obvious that there should be no
      difference between the two types of trials in this regard.

PMID- 1366260
TI  - A case for sublingual captopril.

PMID- 1366261
TI  - The cholinergic nervous system in hypertension: a neglected issue.

PMID- 1366262
TI  - Treating hypertension in older patients.

PMID- 1366263
TI  - Pathologic hypertrophy with fibrosis: the structural basis for myocardial
      failure.
AB  - The major risk factor associated with the appearance of adverse cardiovascular
      events and outcome attributable to cardiovascular disease is left ventricular
      hypertrophy (LVH). Why this should be so resides not in the increase in
      myocardial mass per se, but in the disruption of myocardial structure. An
      abnormal accumulation of fibrillar collagen within the adventitia of
      intramyocardial coronary arteries and neighboring interstitial spaces represents
      such a distortion in structure. Furthermore, this fibrosis disrupts the
      electrical and mechanical behavior of the hypertrophied myocardium. Mechanisms
      responsible for fibrillar collagen accumulation have been examined in intact
      animals and cultured cardiac fibroblasts. In vivo studies indicate that
      myocardial fibrosis is associated with the presence of chronic mineralocorticoid
      excess, relative to sodium intake and excretion, not hemodynamic workload.
      Accordingly, fibrosis can appear in both the hypertensive, hypertrophied and
      nonhypertensive, nonhypertrophied ventricles. In both primary and secondary
      hyperaldosteronism it was possible to prevent myocardial fibrosis with an
      aldosterone receptor antagonist, while in unilateral renal ischemia angiotensin
      converting enzyme (ACE) inhibition was similarly cardioprotective. A regression
      in fibrous tissue and normalization of diastolic stiffness has also been possible
      using ACE inhibition, bringing forward the concept of cardioreparation and the
      notion that heart failure due to fibrosis may be reversible. In vitro studies
      indicate that effector hormones of the renin-angiotensin-aldosterone system
      stimulate fibroblast collagen synthesis. Aldosterone, in pathophysiologic
      concentrations, and angiotensin II, in much larger concentrations, each enhance
      collagen synthesis without altering the mitogenic potential of these cells. Thus,
      elevations in circulating aldosterone and angiotensin II, relative to sodium
      intake, have the potential to not only alter sodium homeostasis and vascular
      tonicity, but also the structure of cardiovascular tissue. Thus, myocardial
      fibrosis represents a structural basis for pathologic hypertrophy and ultimately
      accounts for the appearance of adverse cardiovascular events and outcomes.

PMID- 1366264
TI  - Enhanced blood pressure response to mineralocorticoid stimulation in normotensive
      members of hypertensive families.
AB  - Currently normotensive offspring of essential hypertensive parents often have
      disturbances in blood pressure (BP) regulation such as abnormalities in
      electrolyte homoeostasis, increased salt-sensitivity and/or impaired renal Na(+)
      excretion. Whether an altered reactivity to mineralocorticoids may also play a
      role is presently unknown. Therefore, we investigated BP (recorded during 24 h),
      plasma atrial natriuretic factor (ANF), cyclic guanosine monophosphate (cGMP),
      aldosterone (PA) and renin activity (PRA), 24-h urine electrolyte and cGMP
      excretions measured on 4 consecutive days, as well as other variables, after 1
      week on placebo and after 3 weeks of 9 alpha-fludrocortisone-acetate (9 alpha F)
      administration, 0.6 mg/d in 12 normotensive sons of essential hypertensive
      parents (SEH) and 12 body-mass-index- and age-matched (25 +/- 1[+/-SEM]yr) sons
      of normotensive parents (SN). On placebo, the 2 groups did not differ
      significantly in average 24 h BP (mean BP 95 +/- 2 vs 95 +/- 2 mmHg), plasma-ANF
      (40 +/- 7 vs 30 +5 pg/ml), cGMP (6 +/- 0.4 vs 6 +/- 0.5 nmol/l), PRA (1.3 +/- 0.1
      vs 1.6 +/- 0.2 ng/ml/h), PA (9 +/- 0.5 vs 10 +/- 0.9 ng/dl), hematocrit (44 +/-
      0.7 vs 44 +/- 0.4%) and 96-h urinary-Na+ (mean 205 +/- 13 vs 195 +/- 16 mmol/d), 
      K+ (69 +/- 6 vs 78 +/- 7 mmol/d) or -cGMP (461 +/- 35 vs 483 +/- 32 nmol/d). 9
      alpha F significantly increased BP in SEH (p < 0.005) but not SN (107 +/- 2 vs
      100 +/- 2 mmHg, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1366265
TI  - Metabolic effects of pindolol and propranolol in a double-blind cross-over study
      in hypertensive patients.
AB  - Metabolic effects of pindolol and propranolol were investigated in a randomised
      study of double-blind, double-dummy design in 39 Caucasians with newly detected
      hypertension. Each active treatment period was 6 months long. A euglycaemic
      hyperinsulinaemic clamp test was done to measure insulin sensitivity, and i.v.
      glucose tolerance was investigated with insulin determinations. Lipoprotein
      concentrations were quantified and lipoprotein lipase activities were determined
      in muscle and adipose tissue and in plasma after heparin injection. The blood
      pressure was significantly reduced by both regimes. The insulin sensitivity index
      was decreased by 34% during propranolol treatment and by 17% during pindolol
      treatment. The insulin concentrations in plasma were elevated at the end of the
      i.v. glucose tolerance test but were not high enough to compensate for the
      insulin resistance, so HbA1c and glucose concentrations were increased. A
      significant reduction of lipoprotein lipase activity in skeletal muscle during
      propranolol treatment probably explains the pronounced increase in serum
      triglyceride concentration during propranolol treatment despite lower free fatty
      acids and higher lipoprotein lipase activity in adipose tissue. These changes of
      lipoprotein lipase activity were not correlated to the changes in insulin
      sensitivity. In summary, the metabolic effects were significantly less pronounced
      with pindolol than with propranolol, which probably can be ascribed to the
      agonistic effect of pindolol on beta 2 adrenoceptors.

PMID- 1366266
TI  - [Inefficacy of coronary circulation caused by propofol].

PMID- 1366267
TI  - [Increased risk of leukemias and brain tumors in occupational exposure to
      magnetic fields].

PMID- 1366268
TI  - [Implantable defibrillators: programs and problems].

PMID- 1366269
TI  - [Lambert-Eaton myasthenic syndrome].

PMID- 1366270
TI  - [Various fevers and coronary artery disease].

PMID- 1366271
TI  - [Human insulin and hypoglycemia].

PMID- 1366272
TI  - [Development of collaboration between antenatal care and the delivery hospital].

PMID- 1366274
TI  - [Prolymphocytic leukemia].

PMID- 1366273
TI  - [Encephalitis in children].

PMID- 1366275
TI  - [Ultrasonography-guided biopsies of tumors in the anterior mediastinum].

PMID- 1366276
TI  - [Movement disorders in the spinal joints of the lower back and abnormal EMG
      findings of the back muscles associated with frequent back pain].

PMID- 1366277
TI  - [Epileptic seizures interpreted as being psychogenic].

PMID- 1366278
TI  - [Why would a 2-year-old child with diabetes not want to eat?].

PMID- 1366279
TI  - [Gamma globulin treatment].

PMID- 1366280
TI  - [Frequent stomach aches leading to surgery].

PMID- 1366281
TI  - [Magnetic imaging in practice].

PMID- 1366282
TI  - [Magnetic imaging].

PMID- 1366284
TI  - [Is magnetic imaging worth the cost?].

PMID- 1366283
TI  - [Nuclear magnetic resonance as an examination tool].

PMID- 1366286
TI  - [When is magnetic imaging indicated in central nervous system diseases?].

PMID- 1366285
TI  - [Principles and study techniques of magnetic imaging].

PMID- 1366287
TI  - [Problematic brains of children].

PMID- 1366288
TI  - [Magnetic imaging of the brain in elderly persons].

PMID- 1366289
TI  - [Magnetic imaging as an aid to the otolaryngologist or ophthalmologist].

PMID- 1366290
TI  - [Magnetic imaging of patients with neck and upper extremity symptoms].

PMID- 1366291
TI  - [Imaging of the lower back].

PMID- 1366292
TI  - [Magnetic imaging of bones and muscles].

PMID- 1366293
TI  - [When is it worthwhile to study joints with magnetic imaging?].

PMID- 1366294
TI  - [Magnetic imaging of the heart and blood vessels].

PMID- 1366295
TI  - [Magnetic imaging as an additional tool in clinical assessment].

PMID- 1366296
TI  - [Dictionary of magnetic imaging].

PMID- 1366297
TI  - [Thyrotropin or thyroxin?].

PMID- 1366298
TI  - [Tyrosinemia].

PMID- 1366299
TI  - [Lyme borreliosis].

PMID- 1366300
TI  - [Complement and tissue destruction in heart infarction].

PMID- 1366301
TI  - [Radiologically-guided treatment of chronic lower limb ischemia].

PMID- 1366302
TI  - [Neuroblastoma screening is not needed in Finland].

PMID- 1366303
TI  - [Is short-acting insulin needed in the evening when treating diabetes with
      multiple injections?].

PMID- 1366304
TI  - [Narcolepsy or epilepsy?].

PMID- 1366305
TI  - [Low serum HDL-cholesterol level in a young body-builder].

PMID- 1366306
TI  - [Synovial chondromatosis as a diagnostic puzzle].

PMID- 1366307
TI  - [Imaging of a painful shoulder].

PMID- 1366308
TI  - [Prevention and treatment of osteoporosis. Suomen Akatemia ja Suomalainen
      Laakariseura Duodecim].

PMID- 1366309
TI  - [Anticardiolipin antibodies--detection and diagnostic value].
AB  - Anticardiolipin antibodies belong to a family of antibodies to phospholid and are
      important in pathogenesis of some diseases. Statistically significant high titer
      of circulating anticardiolipin antibodies were found in SLE patients,
      thromboembolic events, thrombocytopenia and recurrent fetal loss. We tested 53
      sera of SLE patients to anticardiolipin antibodies by own modification of ELISA.
      Only two sera were positive, one of them was associated with recurrent fetal loss
      and disease. The incidence of anticardiolipin antibodies in we have found no
      correlation with the activity of to those reported in other studies. Our tested
      sera (4%) was much lower in comparison.

PMID- 1366310
TI  - [Agglutinins in the diagnosis of pertussis].
AB  - The performed investigation showed that the results of agglutination test in
      diagnostics must be explained with reserve as a supplement to the clinical
      picture and the other laboratory findings. Titre must be followed at least for 20
      days on many blood samples. The more reliable diagnosis according to
      agglutination test can be given only if we know in question is a nonimmunized
      child and titre is > or = 1:80. The negative and lower titres cannot exclude or
      confirm the disease.

PMID- 1366311
TI  - [The complement activation system in acute poststreptococcal glomerulonephritis].
AB  - The activation of the complement system is very important part of the immunologic
      process. Measuring levels of products of complement activation is a useful
      diagnostic and prognostic procedure. This report presents the results of a follow
      up of 54 children with acute poststreptococcal glomerulonephritis. At the
      beginning of the disease, all patients (i. e. 100%) had decreased levels of C3
      component of the complement system, and 72.2% patients had decreased levels of
      the haemolytic complement. The mean value of the control measurements increased
      significantly from one measurement to another (with p < 0.01, and within 6 weeks
      after the beginning of the disease, it reached the normal range. According to our
      results, the activation of the complement system was induced by the classical
      pathway. We cannot explain why the component C4 did not take part in it.
      According to the results of the haemolytic assay, the alternative pathway of
      activation was used too. We found that there was a correlation between
      improvement of clinical features and decrease of metabolisation of complement
      components.

PMID- 1366312
TI  - [Morphologic changes in the lung and liver parenchyma in pregnant female rats
      treated with petroleum and trichloroethylene].
AB  - Light and heavy petrols influence as well, as that of trichloroethylene on
      morphological changes in the hepar and lungs of gravid Wistar females was
      investigated. It was found that inhalation of petrols and trichloroethylene in
      small concentrations caused degenerative changes in the hepar parenchyma, while
      there were no changes in the lungs.

PMID- 1366313
TI  - [The significance of synergism between cervical infections and prostaglandins in
      inducing preinduction priming in the 3rd trimester of pregnancy].
AB  - The length of labour and foetal trauma could be significantly reduced by
      reduction of cervical resistance in the cause of labour. It is well known that
      the most effective way of priming is by prostaglandins. Microorganisms of cervico
      vaginal flora, with or without inflammatory component, can produce factors which
      can create predisposition for preterm delivery. Namely, increased levels of
      prostaglandins E2 and F2 alpha could be noticed in amniotic fluids, compared with
      these levels in pregnant women without signs of infection. The study included 60
      parturients with low Bishop score (less then 5), with average gestational age of
      40.5 weeks. Group A: Prepidil gel with 0.5 mg of prostaglandin E2 was applied to
      cause priming. Group B: Half of doses of Prepidil gel (0.25 mg) was applied to
      the 30 patients with clinical signs and with positive laboratory findings of
      cervical infection. After 12 hours all patients were induced with oxytocin. All
      obstetrically important parameters were closely followed in the course of priming
      and induction. Presence of cervical infection could be beneficial, because
      priming can be produced with half of doses of prostaglandin, which means medical
      (reduction of side-effects and dangers of hyperstimulation) and significant
      economical benefits regarding the high price of prostaglandins.

PMID- 1366315
TI  - [Evaluation of pathologic findings in the larynx and pulmonary function].

PMID- 1366314
TI  - [Antithrombin III in chronic renal insufficiency].
AB  - In a group of fourty eight patients with chronic renal failure and a group of
      twenty patients on chronic hemodialysis, we studied the biologic activity of
      Antithrombin III by using immunoelectrophoresis and coagulation methods. We found
      that increased values of biologic activity of Antithrombin III, were significant.
      This can be an additional factor in explaining the origin of bleeding in patients
      with chronic renal failure and uremia without nephrotic syndrome. The index of
      biologic activity of Antithrombin III was significantly decreased after giving
      heparin to the patients with chronic renal failure on hemodialysis. The obtained
      values were low and within the ranges found in patients suffering from
      thrombosis. This decrease in biologic activity of Antithrombin III, together with
      the well known increase in factors of hemostasis during hemodialysis, is an
      important cause of frequent thrombosis, which can be fatal for patients. In the
      same group, antigenic values of Antithrombin III measured before and after giving
      heparin, were not changed. These facts show the necessity of measuring the
      biologic activity of Antithrombin III because the quantity of Antithrombin III is
      not a reliable indicator of its functional validity.

PMID- 1366316
TI  - [Rotaviruses--causes of minor epidemics of diarrheal diseases in the neonatal
      department of the Pediatric Clinic in Sarajevo].
AB  - A rotavirus epidemic took place at the above mentioned department (8. V 1987
      until 19. VI 1987). During that period, 36 newborn infants were treated for
      rotaviral symptoms and they all had their stools checked for rotaviruses or their
      antigen. Rotaviruses were found by 17 patients (47.2%). As a lab method we used
      immunoelectrophoresis. 20 patient of the overall number of 36 were boys and 16
      were girls. Stool samples showed rotaviruses in 9 boys (45%) and 8 girls (50%).
      The age of patients was 3 to 34 days. After 1-14 days all children were well.

PMID- 1366317
TI  - [Microsurgical treatment of tubal factors in sterility].
AB  - In the period from 1982-1988, 164 patients were operated due to the tubal factor
      sterility. Indications for operations were based on HSG and laparoscopy.
      Microsurgical process was applied. 57 (34.75%) of 164 operated patients
      conceived. There were 41 (25.90%) intrauterine and 16 (9.14%) ectopic
      pregnancies. The most frequently pregnancies happened in the patients who had
      been treated by fimbroplasty and isolated adhesiolysis. The patients, who had
      been treated by salpingostomy terminalis and tubal implantation had lower
      pregnancy percentages.

PMID- 1366318
TI  - [Rehabilitation approaches in patients after percutaneous lumbar discectomy].
AB  - The lumbar ache syndrome is more and more getting sign of a social disease
      because of its rate. Beside the conservative treatment very often the operative
      treatment is used too. Except the classical discectomy, a percutaneous lumbar
      discectomy had been used since the last year. In the work we gave the basic
      anatomical characteristics of the spiral column, stages of intervertebral disk
      dislocations and general characteristics of the acute ache syndrome. According to
      Aesculaps prospect we described the operating technique of percutaneous lumbar
      discectomy as well as the rehabilitation treatment of classical and percutaneous
      lumbar discectomy.

PMID- 1366319
TI  - [Anomalies of external genital organs in school-age boys in the first four
      grades].

PMID- 1366320
TI  - [Ergometry testing in the past and today].
AB  - Exercise testing on bicycle-ergometer or treadmill represents a simple and
      relatively cheap medical procedure. It may be managed in any level of medical
      evaluation and especially for discovering persons with low or high cardiac risk,
      beside the asymptomatic or symptomatic status during the testing. The cumulated
      experience gave the proof than the exercise testing is superior to coronarography
      and ventriculography. Test protocol and conclusions must be together with the
      recommendations of the cardiology association and the author gives some of his
      own remarks and practical recommends. In personal everyday practice someone can
      find improvements too.

PMID- 1366321
TI  - [Hemorrhagic fever with renal syndrome--etiology].
AB  - HFRS was confirmed serologically in two patients, who were infected in the
      natural focus near Zupanja. Using the bigger number of virus antigens in indirect
      immunofluorescent antibody test, afterwards was proved the agent could be
      classified into the serotype 3 of Hantaviruses, and antigenically is identical
      with virus NE (strain Hallnas), respectively Yugoslav isolate "Vranica". Serotype
      differentiation of the agent in patient who were infected in the area of Igman,
      near Sarajevo, has not been performed by the same test. There was assumed a
      possibility for circulation of "new", up to now non-identified, serovariant of
      Hantaviruses in this natural focus.

PMID- 1366322
TI  - [Relation of epithelial metaplasia and calcification with epithelial
      proliferation in fibrocytic breast disease].
AB  - By semiserial microscopic investigation of the complete tissue of 65 surgical
      excised fibrocystic lesion of female breast we have found that there exist (a)
      the high frequency (58.5%) of the apocrine metaplastic epithelium, predominantly
      located in lobules and topographically widely distributed (mean 9 focuses on a
      sample), (b) the rare occurrence (3%) of lobular and ductal squamous metaplasia
      and (c) the high frequency (40%) of sparse (mean 3 focuses on a sample) lobular
      calcifications. Statistically, apocrine metaplasia and calcifications were
      significantly (p < 0.001 and p < 0.01) more frequent in the samples of
      proliferative fibrocystic lesions. The level of the positive spacial correlation
      (O = 0.512) of proliferative and apocrine metaplastic epithelial changes, as well
      as a common stratification and papillation of the apocrine epithelium indicate
      indirectly a possible influence of a steroid hormonal unbalance in the promotion
      of the apocrine epithelial metaplasia.

PMID- 1366323
TI  - [A complicated foreign body in the esophagus--case report].
AB  - Our female patient B. V. 47 years old, by eating the fried pork tongue, got
      strangled. Immediately it was accompanied by a very intense, strong pain in the
      lower portion of the neck. Otorhynolaryngologists performed esophagoscopy the
      same day, but corpus alienum was not found. Three days later, the patient came in
      the hospital again, complaining to an intense pain in the lower portion of the
      neck, so that she could not eat anything for three days. Immediately after being
      accepted to the hospital was done Rtg of cervical spine and lungs, as well as Rtg
      of passing through esophagus which demonstrated a piece of metal wire 4 cm in
      length at the level of the second thoracic vertebra. The wire perforated the
      esophagus at both lateral sides. Alter removal of the wire, mediastinitis was
      treated medically.

PMID- 1366324
TI  - [Chronic changes in the liver in our patients].
AB  - VHB infection together with alcohol ist the most important ethiologic factor in
      the genesis of chronic liver parenchyma damage in our sample. Selection of
      patients with chronic diseases of the liver should be done on the basis of
      hepatitis markers determination, that is on the presence of HBsAg and HBeAg and
      the activity of aminotransferases in blood. Doing this it can be seen that more
      that half of the patients with chronic liver damage do not need therapy, and they
      have work capacity preserved. In these cases occasional controls of hepatitis
      markers and the level of AT in blood are needed. Presence of the virus
      replication can be determined on the basis of presence of the HBeAg in blood and
      HBcAg in the hepatocyte nucleus (histologic assay), since HBV-DNA and HBV-DNA
      polymerases in blood are not determined in the day's routine. Biopsy and rebiopsy
      of the liver tissue (pathohistologic assay) is the only confident my to determine
      the degree of liver damage. Introducing of the unique criteria in the management
      of the patients who have the signs of chronic liver damage would lower the
      diagnosis and treatment costs, as well as the unnecessary patient's absence from
      work. Proceeding of the preventive measures, vaccination of the persons who are
      exposed to VHB infection, as well as the struggle against alcoholism, stay on as
      the main source in prevention of chronic liver damage genesis.

PMID- 1366325
TI  - [Morphometric aspects of seminiferous tubules in rats treated with melatonin and
      whole body irradiation (stereologic analysis)].
AB  - The volume density of the seminiferous epithelium, lumen of tubules and the
      testis interstitium in the shampinealectomized adult Wistar rats was determined
      after melatonin treatment and whole-body irradiation with 8 Gy of gamma rays
      produced by 60 Co. The solvent was injected to the control group of animals. By
      the comparison of stereological results, it was shown that melatonin modifies the
      quantitative characteristics of seminiferous tubules reducing the effects of
      irradiation originally produced.

PMID- 1366326
TI  - [Specifics in the treatment of epilepsy in children with mental retardation].
AB  - Authors discuss some specifics in treating epilepsies in children with mental
      retardation that have to be considered. First is the problem of precise
      diagnosis, because of certain phenomena in mentally retarded children, and a
      possibility of the so called pseudoretardation that can be caused by epileptic
      seizures or inadequate medication. A specific problem is vulnerability of these
      patients regarding antiepileptic drugs, especially phenytoin and phenobarbiton.
      Usage of psychopharmacs should be minimized and drugs interaction has to be
      considered permanently. A general trend in treatment should go towards increase
      in usage of carbamazepine and valproic acid, preferring monotherapy.

PMID- 1366327
TI  - [Asymptomatic and manifest forms of listeriosis in neonates].
AB  - Pointed out has been a danger of listeria monocytogenes infections, which is most
      frequently transplacentally transmitted from the mother to the baby. In such
      cases, it results in early, septic forms with disseminated abscesses and
      granulomas in many organs. A case with a positive outcome has been described.
      Infection incited during delivery or soon after it results in late, meningitic
      form of listeriosis, which is characterized with a high mortality outcome. Such a
      case that resulted in death has also been described. Three children infected by
      listeria remained asymptomatic. Pointed out has been the inevitability of
      antibiotic treatment of such children, too, to prevent listeria from developing
      septic meningitic form. Imperative to prevent nosocomial listeria infections in
      obstetric wards, which is a reality, are strict measures of hygiene.

PMID- 1366328
TI  - [Effects of nifuroxazide (Ercefuryl), trimethoprim-sulfamethoxazole and
      bactisubtil in acute diarrhea].
AB  - The clinical effects of Nifuroxasid (N), Trimetoprim sulphametoxasol (TS) and
      Bactisubtil (B) on bacillar dysentery and alimentary toxicoinfections in the
      patients treated at the Clinic from January 1984 to the end of December 1989 have
      been analysed. According to the clinical signs, patients have been divided in ten
      categories of light, mild and heavy forms. In total, 329 cases of bacillar
      dysentery and 89 cases of alimentary toxicoinfections have been analysed. The
      following was established: A. Bacilar dysentery: the fastest normalization of the
      stool was achieved with N in every clinical form (averages 2.2, 3.5 and 4.05
      days). With TS the effects were slower (3.0, 3.9 and 4.4 days), but the slowest
      normalization was recorded with B (3.4, 4.6 and 5.4 days). However, with TS, some
      Shigella strains showed resistance (in 23 out of 94 antibiograms), which
      diminished the effects. B. Alimentary toxicoinfections were treated only with N
      and B, since these forms of diarrhea caused by toxigenic factors were milder.
      Better results were achieved with N in this case as well.

PMID- 1366329
TI  - [Acute viral hepatitis--present status and perspectives].
AB  - Recent advances in epidemiology, virology, of clinical of hepatitis are presented
      in the paper. The authors pointed out that hepatitis A never becomes chronic. On
      the other hand, with hepatitis B or B and D, evolution to chronicity is possible.
      Two distinct forms of non-A non-B hepatitis are now distinguished: parenterally
      transmitted non-A non-B hepatitis, mainly due to hepatitis C virus; enterically
      transmitted non-A non-B hepatitis mainly due to hepatitis E virus. C virus
      hepatitis is characterized by a frequent course to chronic hepatitis, cirrhosis
      and hepatocellular carcinoma. Chronic forms are associated with the presence of
      anti-HC antibodies in the serum. These antibodies are rarely present in the acute
      stage of the disease. Hepatitis E is almost exclusively encountered in developing
      countries. Like with A virus hepatitis, chronicity never occurs. However,
      fulminant hepatitis is possible in pregnant women in the third trimester of
      pregnancy. There is no routine serological test. Development of vaccines against
      A, E and C viruses can be expected very soon. There is no specific treatment of
      acute viral hepatitis.

PMID- 1366330
TI  - [Body weight loss with the aid of alginic acid].
AB  - The researchers were done in the Counselling Service for Nutrition of the
      Institute of Hygiene in Sarajevo. The voluntary group of researched persons was
      treated regarding the body weight. The corpulance was for about 25-30% (percent)
      higher than it was normal for the persons with their individual characteristics-
      sex, age, height and body constitution. The investigated persons were classified
      into two groups--the experimental group A, one to which besides diet the
      reduction the "Alginete" pills were given helping the (acceleration) process of
      weight reduction--losing weight. The controlling group was only an individual
      reduction diet. The way and the results of standing the diet were given in the
      work.

PMID- 1366331
TI  - [Abuse of cannabis preparations].
AB  - The author reviews the basic features, nature of action and the effects of the
      canabis drugs (hashish and marijuana) on human organism. The review starts with
      the well known fact that these kinds of drugs are the oldest ones and the most
      widely known to the civilization. It reviews in details very wide effects of the
      canabis drugs on the mental functions as well as the clinical expression of that
      action, where the basic mechanisms dominate: euphorogenic, sedative and
      psychodelic. With a detailed description of all psychopathological phenomena that
      appear in the chronic hashish and marijuana addicts, where the amotivation
      syndrome and flash back are particularly pointed out.

PMID- 1366332
TI  - [Evaluation of health legislation within the context of the goals and strategies
      for "Health for All by the Year 2000" in Bosnia and Herzegovina].
AB  - In this paper significant changes have been presented concerning to the health
      legislation of Bosnia and Herzegovina in the period from 1970 till today. These
      changes could have had an effect on the changes in the health system as well as
      in the health status of the population. This is all aimed at achieving strategy
      and targets for Health for All by the year 2000. Certain systematic solutions for
      achieving strategy and targets exist in the health legislation of Bosnia and
      Herzegovina (Law on health care the 1986), but they are set without clear content
      and holders of office. We could notice the absence of legislative support for
      resolving group of targets 13-17 and partially 32-38.

PMID- 1366333
TI  - [Evaluation of citizen satisfaction with the organization of the primary health
      care system].
AB  - The state of organization and distribution of PHC networks in our Republic is not
      satisfactory. It is so mostly for the reason of absence of extramural PHC units
      in settlements, schools, and working collectives, i.e. unavailability of health
      care to the people and closeness of the health care system. A poll carried out
      among 1859 patients in the health centre waiting rooms in Bosnia and Herzegovina
      has shown that only 35.1% of the polled citizens--health care beneficiaries are
      satisfied with the work of doctors and nurses in PHC surgeries. The poll has also
      shown that about 65% of the patients of all age groups realize the health care
      protection only after long waiting and with some other difficulties. Then, 96% of
      the out-patients expressed their dissatisfaction with the organization of PHC,
      either owing to frequent changes of physicians, i.e. health personnel, or to
      inadequate working hours, waiting long etc. Only 6.5% of the polled patients said
      there were satisfied with the work of PHC service and did not ask for changes in
      the structure. The author in his paper quotes the principles on which a good PHC
      service should be based and proposes adequate measures for its promotion.

PMID- 1366335
TI  - [Traditional medicine in the Cazinska region from 1790 to 1878].
AB  - The inhabitants of Mala Kladusa are mostly refugees from Cetingrad and Dreznik,
      and between 1790 and 1878 they had chances to cure more than 1200 wounded and a
      few thousand ill people in barber's shops in Gornja and Donja Baraka. Gornja and
      Donja Baraka are good places for hospital (barber's shop) because they are near
      the river Kladusnica, and in the wood. In barber's shop worked a barber who cured
      people and also prepared cures from local herbs. Also barber's wore bags with
      cures and medical instruments, and had duty to help people even if it was against
      law or patient was poor.

PMID- 1366334
TI  - [Development of health care services in Bosnia-Herzegovina during the Ottoman
      empire].
AB  - Organized health service in Bosnia and Herzegovina practically started by the
      treatment of the sick in the Hadji Sinan's Tekke that was founded in 1768. Before
      that, the civilian population had been mainly treated in their homes, while the
      army were treated in barracks or hired hans (inns). As late as the nineteenth
      century, health care was provided by quack doctors, treating physicians or
      surgeons and barbers, who were trained, beside the circumcision of male children,
      for tooth extraction, broken bone setting, and sometimes even for performing
      minor surgical operations (a specially trained barber called djerah). The first
      trained medical personnel were the Franciscans and Jews, who studied at the
      Universities of Italy, Austria, Hungary etc. The first Muslim trained physicians
      studied at the Medical Faculty in Istanbul. The first ones were: Dr. Mehmed
      Serbic and Dr. Zarif Skender, while the first Bosnian graduate in pharmacy was
      Jakov Sumbul. In Sarajevo and Bosnia and Herzegovina worked many a doctor who
      came from abroad. The majority of them converted to Islam and worked in the
      barracks, and later on in the Turkish Military Hospital when it was founded in
      Sarajevo. All of them played an important role in the prevention and treatment of
      the most frequent mass infectious and non-infectious diseases that were raging
      among the population--plague, cholera, syphilis, leprosy, tuberculosis, fungoid
      diseases etc.

PMID- 1366336
TI  - [Arterial aneurysms].
AB  - The author analysed etiology, morphology, localization, symptomatology,
      diagnostics and surgical methods of treatment in 63 patients with 81 arterial
      aneurysms. Arterial aneurysms are not rare in vascular pathology. Most of them
      are atherosclerotic etiology (62%). Abdominal aorta is the most frequent
      localization (49%). Symptomatology and clinical findings depend on the
      localization, size and complications. Echosonography, with clinical finding, has
      presented the most accurate diagnostic procedure. Surgery is the method of the
      treatment of such patients, but the optimal method is the aneurysmectomy or
      resection of aneurysm with arterial reconstruction.

PMID- 1366337
TI  - [Urinary infections during pregnancy and methods of prevention].
AB  - Urinary tract infections in pregnant women develop owing to the short urethra in
      women, mechanical pressure of the uterus onto atonic urethra during pregnancy,
      atony of the urinary bladder caused by the level of progesterone, iatrogenic
      factors (catheterization), some metabolic disorders, anemia, obstipation etc.
      These are frequent reasons why pregnant women over the pregnancy period develop
      infections of urinary tract, where a significant number of them have bacteriuria
      showing no symptoms of acute infection whatsoever. The research covered
      unselectively 4,850 urine samples of pregnant women. The results obtained by
      classical methods--taking urinoculture and doing antibiogramme--have shown that
      in this sample there is a large number of asymptomatic bacteria (13%), which is
      complicated by an increased incidence of pyelonephritis gestoses in the second
      half of the pregnancy. In our sample, the commonest cause of urinary infections
      has been E. Coli, then the second trimester of risk gestation period; the risk
      group with regard to parity are primiparas, while the risk age is between 20 and
      29.

PMID- 1366338
TI  - [Significance of two-dimensional echocardiography in the diagnosis of mitral
      valve calcification--sensitivity and specificity].
AB  - The effect of two-dimensional echocardiography in assessment mitral valve
      calcifications was compared to computed tomography (CT) in 50 patients with pure
      rheumatic mitral stenosis (MS). Echocardiography revealed no mitral
      calcifications in 23 patients, respectively 46 per cent (grade 0). Twelve
      patients (24 per cent) had calcifications smaller than 2.5 mm (grade 1). Eleven
      (22 per cent) had moderate calcifications, smaller than one half of length of the
      anterior mitral leaflet (grade 2) and four (8 per cent) had calcifications larger
      than one half of the length of the anterior mitral leaflet (grade 3). The last
      two groups were thought to have clinically important calcifications. Specificity
      and sensitivity were examined in comparison to CT. By echocardiography, five (ten
      per cent) false positive findings were found in the group 2. There were neither
      false positive nor false negative findings in the last two group. The first group
      when compared with other three groups showed sensitivity of 100, specificity of
      85, and predictive accuracy of 81 per cent. But the first two groups together
      compared with the last two groups showed sensitivity, specificity and predictive
      accuracy of 100 per cent.

PMID- 1366339
TI  - Alignment, classification, and three-dimensional reconstruction of single
      particles embedded in ice.
AB  - Cryo-electron microscopy of single biological particles poses new challenges to
      digital image processing due to the low signal-to-noise ratio of the data. New
      tools have been devised to deal with important aspects of 3-D reconstruction
      following the random-conical data collection scheme: (a) a new shift-invariant
      function has been derived, which promises to facilitate alignment and
      classification of single particle projections; (b) a new method of orientation
      search is proposed, which makes it possible to relate random-conical data sets to
      one another prior to reconstruction; and (c) the foundation is laid for a 3-D
      variance estimation which utilizes the oversampling of 3-D angular space by
      projections in the random-conical reconstruction scheme.

PMID- 1366340
TI  - Three-dimensional crystallographic reconstruction for atomic resolution.
AB  - Three-dimensional structures have recently been determined by electron
      crystallography at a resolution high enough to determine atomic arrangements in
      both protein and mineral specimens. The different nature of these two types of
      specimens produces some very significant differences in the way data is obtained
      and processed, although the principles are the same. The sensitivity of proteins
      to damage by the electron beam limits the signal-to-noise ratio in the image and
      the resolution to which data can be extracted from the image. A number of
      constraints, such as the amino acid sequence and the connectivity of atoms within
      amino acids, can be used in interpreting the limited image data. In materials
      samples, the relative insensitivity to damage allows obtaining resolution limited
      only by the microscope. In many samples, dynamical scattering and other non
      linear effects limit the information in the image, but this limit can be
      circumvented by working in very thin areas of the specimen.

PMID- 1366341
TI  - Confocal microscopy and three-dimensional reconstruction of thick, transparent,
      vital tissue.
AB  - The three-dimensional visualization of the 400 micron thick, transparent, in situ
      cornea is described to demonstrate the use of confocal light microscopy for
      noninvasive imaging of living cells and thick tissues in their normal, vital
      conditions. Specimen preparation and physiological stability, as well as light
      attenuation corrections are critical to data acquisition. The technique to
      provide mechanical stability of the specimen during the duration of the image
      acquisition is explained. A laser scanning confocal light microscope (LSCM) was
      used to obtain optical serial sections from rabbit eyes that were freshly removed
      and placed in a physiological Ringer's solution. This study demonstrates the
      capability of the confocal light microscope to obtain a series of high contrast
      images, with a depth resolution of one micron, across the full thickness of
      living, transparent tissue. The problems of nonisotropic sampling and the limited
      eight-bit dynamic range are discussed. The three-dimensional reconstructions were
      obtained by computer graphics using the volume visualization projection
      technique. The three-dimensional visualization of the cornea in the in situ eye
      is presented as an example of image understanding of thick, viable biological
      cells and tissues. Finally, the criterion of image fidelity is explained. The
      techniques of confocal light microscopy with its enhanced lateral and axial
      resolution, improved image contrast, and volume visualization provides
      microscopists with new techniques for the observation of vital cells and tissues,
      both in vivo and in vitro.

PMID- 1366342
TI  - Early diagnosis of anaphylactic reactions to neuromuscular blocking drugs.
AB  - Neuromuscular blocking drugs (NMB) are involved in most of the anaphylactic
      reactions occurring during anaesthesia. Patients are evaluated usually 6 weeks
      after the reaction, by skin testing. In order to obtain an earlier diagnosis, we
      have measured plasma concentrations of histamine, tryptase and NMB-specific IgE
      antibodies in 14 patients after an anaphylactoid reaction. We have compared the
      results with those of skin tests and specific IgE obtained 8 weeks later. Good
      agreement was observed in all subjects between the results of skin tests and the
      values for histamine and tryptase, provided that both markers were measured
      simultaneously. Furthermore, there was no significant difference between the
      concentrations of NMB-specific IgE antibodies observed at the time of the
      reaction and 8 weeks later. Thus anaphylaxis to neuromuscular blocking drugs can
      be demonstrated at the time of the reaction by measuring plasma concentrations of
      histamine, tryptase and specific IgE. In the event of the patient's death, such
      measurements may be useful in identifying the likely cause.

PMID- 1366343
TI  - Renal stone disease in the 1990s: the powder keg and tinderbox theory.
AB  - Abnormal dietary habits that lead to hypercalciuria, hyperoxaluria,
      hypereruricosuria, and hypocitraturia do not always result in nephrolithiasis. A
      concept is emerging according to which, to account for renal stone formation in
      the face of the aforementioned biochemical disorders, one must search for
      underlying conditions in patients with the disease. Work carried out over the
      past few years and reviewed herein definitely supports this idea and includes the
      following processes: 1) interleukin-1 production by monocytes to augment the
      impact of dietary hypercalciuria; 2) disturbed activation of pyridoxine to
      pyridoxal 5'-phosphate to aggravate dietary hyperoxaluria; 3) abnormal intestinal
      transport of citrate to aggravate dietary hypocitraturia; 4) molecular
      abnormalities of glycoprotein inhibitors to aggravate the promotive effect of the
      diet on urinary crystallization; and 5) renal tubular lesions to favor particle
      retention and stone formation. This article reviews the most recent literature
      and discusses the author's "powder keg and tinderbox" theory of idiopathic
      calcium stone disease.

PMID- 1366344
TI  - [Associations among non-metric features of the atlas in the human species].
AB  - Six non-metrical variants has been studied in a series of 500 human atlases. A
      bipartition of the superior articular facet has been observed in 20.8% of cases,
      a posterior ponticulus in 14.2% of cases, a retrotransverse ponticulus in 14.2%
      of cases, an anterior dehiscence of the foramen tranversarium in 10.2% of cases,
      a dehiscence of the posterior arch in 2.8% of cases, and a lateral ponticulus in
      1.8% of cases. Bilateral occurrence has been noted in 42.2 to 46.2% of cases for
      the anterior dehiscence of the foramen transversarium, the posterior ponticulus,
      and the bipartition of the superior articular facet. Bilateral occurrence is less
      frequent for the retrotransverse ponticulus (29.6%), and particularly for the
      lateral ponticulus (11.1%). The incidence of a given lateral character according
      to the side has been found identical or similar on the left and on the right
      sides. In the present series, 51.6% of the atlases showed none of the six
      variants studied; 46.8% of the atlases showed one or two variants; and only 1.6%
      of the atlases showed more than two variants; any cases with more than four
      variants were observed. The most interesting association observed is the
      association of the lateral ponticulus with the posterior ponticulus.

PMID- 1366345
TI  - The floor of the fourth ventricle in the perinatal period in humans: new
      morphological findings.
AB  - The floor of the fourth ventricle is generally believed to show basically adult
      morphological characteristics in man by the perinatal period. This descriptive
      study and statistical analysis of 163 brainstems from human fetuses and neonates
      demonstrates that in this period, the floor of the fourth ventricle presents a
      series of folds and grooves of variable size and sequence, which during the
      perinatal period clearly increase the surface area of the germinal layer
      overlying them. These features are not seen in adults.

PMID- 1366346
TI  - [Methods for the anthropologic and teleradiographic study of the pterygoid
      process].
AB  - The relationships of the external pterygoid plate with the other components of
      the craniofacial building has hardly been explored because of recording
      difficulties. A method to accurately identify in a reproducible way the main axis
      of the pterygoid process with the help of two small iron balls was contrasted
      with other methods seen in the literature. The iron balls technique was shown to
      be the method of choice with regard to biostatistical consistency.

PMID- 1366347
TI  - Variations of the pronator teres muscle: predispositional role to median nerve
      entrapment.
AB  - The variability of the human pronator teres muscle is studied in 60 upper limbs.
      The humeral head was present in all cases and was double in 3 cases (5.0%). The
      ulnar head was present in 47 cases (78.3%). The ulnar head was muscular in 11
      cases, tendinous in 6 cases, and mixed in 30 cases. The collateral branches of
      the median nerve destined to the pronator teres muscle were found to be arranged
      in three main patterns: arising directly from the median nerve, arising from the
      superficial flexor antebrachial muscles nerve, and mixed type. Special reference
      is made to the influence of variations in the pronator teres muscle on the
      compression or the entrapment of the median nerve (pronator syndrome). The
      proposed determinant variations are: short and tendinous ulnar head, ulnar head
      joined to the arch of the flexor digitorum superficialis muscle, ulnar head with
      triple origin slips, and humeral head perforated by the median nerve.

PMID- 1366348
TI  - [Left caudal vena cava: report of a case].
AB  - The infrarenal part of the vena cava inferior running at the left side of the
      abdominal aorta has been observed in a 70 years old caucasian man without any
      other anomaly in the position of the abdominal viscera. This atypical vascular
      pattern was associated with the persistence of a rudimentary right inferior vena
      cava corresponding to the right supracardinal vein. The embryonic origin of this
      anatomical variation and its clinical importance are discussed.

PMID- 1366349
TI  - [Relative growth of the human cerebellum: a quantitative estimate].
AB  - The relative growth of the cerebellum was studied in 300 human foetuses by using
      of the equation Y = bxk. The cerebellum weight was correlated to the cephalic
      perimeter and to the fetal weight. The relative growth of the cerebellum
      presented positive allometry (k = 3.3; k = 1.3 respectively). Masculine foetus
      presented greater index than feminine foetus.

PMID- 1366350
TI  - [Prenatal growth of the human skull: quantitative study].
AB  - The relative growth of the skull was studied in 300 human foetuses by using of
      the allometric equation Y = aXb. The skull growth was correlated to the crown
      rump length and to the fetal weight. The relative growth of the skull presented
      positive allometry. Masculine foetus presented greater index than feminine
      foetus.

PMID- 1366351
TI  - Acetylcholinesterase activity in the human subfornical organ.
AB  - The acetylcholinesterase activity (AChE) in the human subfornical organ (SFO) was
      detected by the method of Koelle and Friedenwald in 16 human brains collected
      between 6 and 12 hrs postmortem. The only AchE-positive structures found were
      neuronal cell bodies and processes, morphologically classified as stellate and
      fusiform neurons of large, medium and small size. Large ones prevailed in the
      dorsal zone. The neurons were homogeneously distributed in the rostral area of
      the SFO. The penetration and ramification of large blood vessels produced a
      decreasing neuronal density in the medium-caudal area. The architecture of the
      SFO in sagittal sections comprised a central zone with neurons juxtaposed to the
      walls of the vascular plexus, whose dendritic and axonal processes showed an
      intricate pattern without a special arrangement. This neuronal zone of the SFO
      was surrounded by a peripheral layer of neurons with axonal projections to the
      rostral area. This layer was thicker in the dorsal zone of the SFO, where axonal
      fibers "climbing-up" from the central perivascular neurons could be demonstrated.
      In coronal sections some neurons with prolongations of arcuate distribution
      connected the dorsal and ventral zones.

PMID- 1366352
TI  - [Demonstration of sensor nervous endings in the rat thyroid gland].
AB  - The nerve sensitive endings or receptors of the thyroid gland have been studied
      in twenty adult male rats. Their morphology, their acetyl-cholinesterase specific
      activity, their mono-amino-oxidase activity and VIP were investigated. Few but
      constant nerve sensitive endings were observed in the thyroid gland. These
      receptors were subdivided by their morphology in the next groups: pear-shaped
      receptors with capsule; capsuled spherical receptors located near vascular walls;
      ovoidal receptors with capsule and glomerular structure; simple or complex mace
      shaped receptors without capsule. The acetyl-cholinesterase technique could just
      show a unique type or receptor, which corresponds with last one described. The
      mono-amino-oxidase technique can not show any type of receptors. VIP was not
      localized immunohistochemically in the sensitive endings of the thyroid gland.

PMID- 1366353
TI  - Histophysiological studies on sex steroid induced changes in the interrenals of
      the male frog Rana cyanophlyctis (Schn.).
AB  - Administration (i.m.) of either estradiol-17 beta (0.5 microgram/frog) or
      progesterone (10 micrograms/frog) on alternate days for 15 days to adult male
      frogs induced the following changes in the interrenal cells: i) nuclear and
      cellular hypertrophy, ii) increase in the activity of delta 5-3 beta-hydroxy
      steroid dehydrogenase and iii) decrease in sudanophilic lipid droplets. Treatment
      with testosterone propionate (100 micrograms/frog) dit not elicit marked changes
      in the above parameters. These results demonstrate that some sex steroids modify
      the interrenal gland steroidogenic activity in R. cyanophlyctis.

PMID- 1366355
TI  - Mammalian cell separation using unit gravity sedimentation.

PMID- 1366354
TI  - Capillary zone electrophoresis: some promising pharmaceutical applications.

PMID- 1366356
TI  - A positive outlook for biotechnology.

PMID- 1366357
TI  - Patenting EPO analogs: screening vs. predictability.

PMID- 1366358
TI  - Engineering resistance to mixed virus infection in a commercial potato cultivar:
      resistance to potato virus X and potato virus Y in transgenic Russet Burbank.
AB  - Potato virus X (PVX) and potato virus Y (PVY) infection in potato may result in
      the loss of certification of seed potatoes and affect quality and yield of
      potatoes in commercial production. We transformed a major commercial cultivar of
      potato, Russet Burbank, with the coat protein genes of PVX and PVY. Transgenic
      plants that expressed both CP genes were resistant to infection by PVX and PVY by
      mechanical inoculation. One line was also resistant when PVY was inoculated with
      viruliferous green peach aphids. These experiments demonstrate that CP protection
      is effective against mixed infection by two different viruses and against
      mechanical and aphid transmission of PVY.

PMID- 1366359
TI  - Rabbit beta-casein promoter directs secretion of human interleukin-2 into the
      milk of transgenic rabbits.
AB  - To test the potential usefulness of transgenic rabbits as production systems for
      human proteins of pharmaceutical value, we cloned the rabbit beta-casein promoter
      and fused it to the genomic sequence of the human interleukin-2 (hIL2) gene. Four
      transgenic female rabbits were tested for expression and biological activity of
      the foreign protein in their milk. The milk of all four females proved to contain
      biologically active hIL2. The results show that transgenic rabbits may represent
      a convenient and economic system for the rapid production of biologically active
      protein in milk.

PMID- 1366360
TI  - Automated laser-fluorescence sequencing.

PMID- 1366361
TI  - Microbial glycolipid production under nitrogen limitation and resting cell
      conditions.
AB  - Rhodococcus erythropolis is able to synthesize an anionic trehalose-2,2',3,4
      tetraester during cultivation on n-alkanes. Preconditions for an overproduction
      are nitrogen limitation, temperature- and pH-shift. The optimum carbon source was
      technical grade n-C-10, which led to 0.35 g g-1 of glycolipid per n-alkane.
      Electron microscopical observations showed that n-C-14,15 (technical grade) grown
      cells contained numerous lipid inclusions in contrast to n-C-10 (technical grade)
      grown cells. Nocardia corynebacteroides synthesizes a novel pentasaccharide lipid
      and as size products small amounts of trehalose-corynomycolates. Optimum
      precursors for overproduction are n-alkanes from n-tetradecane to n-hexadecane
      with yields in the range of 0.17 g g-1 of glycolipid per carbon source.

PMID- 1366362
TI  - Immobilization of enzymes with polyaziridines.
AB  - A novel method of enzyme immobilization using a low molecular weight prepolymer
      of tri-functional aziridines which can immobilize enzymes both by covalent
      attachment and entrapment within a gel matrix is described. The enzymes are
      immobilized on a solid support and exhibit an excellent retention of enzymatic
      activity. The immobilization procedure is essentially a single step process which
      can be easily performed at room temperature or 4 degrees C in either aqueous
      solution or in an inert organic solvent. The polyaziridines used in the
      immobilization are nontoxic, available in bulk at low cost and completely
      miscible with water and many organic solvents, thus providing one of the most
      satisfactory methods of immobilization available.

PMID- 1366363
TI  - Continuous itaconic acid production by immobilized biocatalysts.
AB  - The continuous itaconic acid production from sucrose with Aspergillus terreus TKK
      200-5-3 mycelium immobilized on polyurethane foam cubes was optimized in column
      bioreactors using statistical experimental design and empirical modelling. The
      highest itaconic acid product concentration calculated on the basis of the
      obtained model was 15.8 g l-1 in the investigated experimental area, when sucrose
      concentration was 13.5%, aeration rate 150 ml min-1 and residence time 178 h.
      From sucrose with immobilized A. terreus TKK 200-5-3 mycelium itaconic acid
      production was stable for at least 4.5 months in continuous column bioreactors.
      In comparison, using glucose as substrate and immobilized A. terreus TKK 200-5-1
      mycelium as biocatalyst similar stability was obtained with higher product
      concentration. The omission of copper sulphate from the production medium gave
      the highest itaconic acid product concentration (26 g l-1) from 9% glucose with
      0.25% ammonium nitrate and 0.095% magnesium sulphate.

PMID- 1366364
TI  - Trimethyl lead degradation by free and immobilized cells of an Arthrobacter sp.
      and by the wood decay fungus Phaeolus schweinitzii.
AB  - The continuing production of leaded petrol generates liquid wastes containing
      recalcitrant trialkyl lead, for which no suitable chemical treatment has been
      formulated. This investigation explores the feasibility of using microorganisms
      to catalyse the rate-limiting step of trimethyl lead degradation to dialkyl lead;
      this disproportionates chemically to give, ultimately, Pb2+ which is treatable by
      classical methods. An Arthrobacter sp. and a wood decay macrofungus, Phaeolus
      schweinitzii provide novel evidence for metabolic trimethyl lead (Me3Pb+)
      degradation. The retention of this activity in immobilized cell column reactors
      challenged with Me3Pb(+)-supplemented flows suggests that a future biotreatment
      process may be possible.

PMID- 1366366
TI  - DSIR biotechnology.

PMID- 1366365
TI  - Thermodynamic evidence of trophic microniches in methanogenic granular sludge-bed
      reactors.
AB  - The Gibbs free energy changes in methanogenic granular biomass from sludge-bed
      reactors were evaluated using the in situ concentrations and partial pressures of
      metabolites during the metabolism of acetate, hydrogen, formate and propionate.
      Based on mass balance calculations it appeared that the degradation of propionate
      into acetate, hydrogen and bicarbonate was endergonic, even if propionate was
      effectively degraded. On the other hand, the methane-producing reactions, both
      from acetate and from hydrogen plus bicarbonate, were found to be exergonic and
      the free energy change was sufficient for the formation of ATP. Formate was
      detected in only one of the two reactors. When formate, instead of hydrogen, was
      considered as the electron carrier between propionate-degrading and methanogenic
      bacteria, similar thermodynamic results were obtained. The existence of trophic
      microniches in the granular biomass is suggested to explain propionate
      degradation even though the Gibbs free energy change in the liquid surrounding
      the granules was positive. Hence, to make propionate degradation exergonic the
      dissolved hydrogen concentration surrounding the propionate-degrading bacteria
      would have to be about 30 times lower than in the free liquid.

PMID- 1366367
TI  - Educating the public about biotechnology.

PMID- 1366368
TI  - Market trends for new biotechnology products in South-east Asia.

PMID- 1366369
TI  - Hyaluronic acid--a versatile biopolymer.
AB  - Since its discovery from bovine synovial fluid, hyaluronic acid has found
      application in several diverse areas. It is now extensively used in ophthalmic
      surgery, in the treatment of lameness in racehorses and as an ingredient in
      cosmetics. It can also be used in drug delivery, orthopedics, cardiovascular aids
      and in wound healing. Even so, its potential as a therapeutic agent is yet to be
      fulfilled. New improved products, formed by crosslinking hyaluronic acid with
      itself or other chemicals, are being produced. Hyaluronic acid is clearly a most
      valuable therapeutic biopolymer. This article reviews the properties of
      hyaluronic acid, its biosynthetic pathway and its methods of commercial
      production, and provides an estimation of its current and future world demand.
      Experiments designed to improve production economics have been performed in our
      laboratory. These involved control of glucose and yeast extract concentrations
      and fermentation pH. Hyaluronic acid production by Streptococcus zooepidemicus
      was found to be lower at pH 6.5 than at pH 7.1. A new method of extending the
      production of hyaluronic acid by S. zooepidemicus into the stationary phase has
      also been achieved.

PMID- 1366370
TI  - Preclinical safety evaluation of pharmaceuticals for the world market.

PMID- 1366372
TI  - Coogee Biotechnology Park. Modern bioprocessing in action.

PMID- 1366371
TI  - Strategy for the development of biotechnology in Asia.

PMID- 1366373
TI  - How ANUTECH transfers technology.
AB  - In summary, we would draw your attention to the things that are important, when
      transferring technology from a higher education institution. 1. The institute
      should have a separate department to deal with these matters. 2. We see
      advantages in this being a private company. 3. The type of agreements should be
      flexible so that most projects can be accommodated and having specialized staff
      helps.

PMID- 1366374
TI  - A TAFE strategy for biotechnology skills training.
AB  - The outline of a strategy for training technicians who will undertake
      biotechnology-oriented tasks as employees is the focus of this review. Technical
      and Further Education (TAFE) in Western Australia has recently restructured
      electives offered in certificate and diploma courses of Applied Science. The aim
      of restructuring was to allow a broader choice catering for specialized streams.
      With a few additions it would be possible to list a set of biotechnology options
      for technicians specializing in this area. After identifying employers in Western
      Australia, data on technician employment characteristics and training needs was
      gathered through a survey and used to formulate a future development strategy. In
      the past little attention has been given anywhere in Australia to the training
      needs of this group. The availability of such appropriately trained employees
      will increasingly be recognized as a vital link in the success of any
      biotechnology enterprise.

PMID- 1366375
TI  - Characterization of peptidyl-nucleoside antifungal antibiotics from fermentation
      broth.
AB  - Characterization of sinefungin related antifungal antibiotics from fermentation
      broth was accomplished by coupling photodiode array (PDA) detection to high
      performance liquid chromatography (HPLC). From the combined HPLC-PDA evaluation
      of broth filtrate, we detected five sinefungin related components. Fast atom
      bombardment (FAB) mass spectroscopic evaluations, mass-analysed ion kinetic
      energy spectra (MIKES) and collision activated (CA) MIKES of these components
      confirmed their respective identities. Our findings from the combination of HPLC
      photodiode array acquisition and FAB-mass spectrometry suggest we have detected
      the presence of a previously unreported sinefungin analogue.

PMID- 1366376
TI  - Environmental factors influencing methanogenesis in a shallow anoxic aquifer: a
      field and laboratory study.
AB  - The environmental factors influencing methanogenesis in a shallow anoxic aquifer
      were probed in a combined field and laboratory study. Field data collected over a
      year revealed that 'in situ' rates of methane production were depressed in winter
      and elevated in summer. Over the same period, ground water pH values ranged from
      6.0 to 7.8 while temperatures varied from 7-22 degrees C. 'In situ'
      methanogenesis was severely inhibited at temperatures less than 13 degrees C or
      by pH values less than 7. The influence of these factors on microbial methane
      formation from both endogenous and exogenous substrates were tested in aquifer
      slurries adjusted to pH 5-9 and incubated at temperatures ranging from 5-45
      degrees C. Temperature optima for methane production from endogenous substrates
      varied as a function of pH, but the pH optimum was 8 at all temperatures. Optimal
      conditions for acetoclastic methanogenesis were found at pH 8 and 35 degrees C.
      An analysis of variance revealed that pH, temperature, and a pH-temperature
      interaction are all significant variables influencing aquifer methanogenesis. In
      addition transient sulfate accumulations were also found to limit methane
      production in some areas. A comparison of field and laboratory methane production
      patterns suggest that pH, temperature, and sulfate accumulations are important,
      but not the only environmental variables influencing the mineralization of
      organic matter in shallow aquifers.

PMID- 1366377
TI  - Characterization of the requirements and substrates for reductive dehalogenation
      by strain DCB-1.
AB  - An obligately anaerobic bacterium known as strain DCB-1 was grown under a variety
      of conditions to determine the requirements for dehalogenation as well as factors
      which stimulated or inhibited the process. Dechlorination was obligately
      anaerobic since introduction of O2 immediately inhibited the reaction. Sulfuroxy
      anions, which also serve as electron acceptors for DCB-1, inhibited
      dechlorination but NO3- and fumarate did not. The optimum growth medium for
      dechlorination was 0.2% Na pyruvate and 20% rumen fluid in basal salts. Media
      with either pyruvate or rumen fluid alone did not support dechlorination. DCB-1
      also consumed H2 but typical substrate concentrations of H2 (80 kPa) delayed
      dechlorination. Once the H2 concentration was reduced to less than 20 microM
      (2.67 kPa), dechlorination resumed. Dehalogenation by DCB-1 was restricted to the
      meta substituted benzoates as halogens in other positions and chloroaromatic
      compounds with other functional groups were not dechlorinated.

PMID- 1366378
TI  - Antibiotic sensitivity testing of bacteria by microcolony inhibition and image
      analysis.
AB  - A rapid method for determining the sensitivity of Staphylococcus aureus to beta
      lactams is described. The method involves the culture of microcolonies of the
      bacterium on the surface of antibiotic-containing agar medium on microscope
      slides. The areas of the microcolonies formed are measured by means of a
      microscope and image analyzer. The sensitivity of the bacterium can be estimated
      in 4 h by this technique and the results are comparable to those obtained by
      overnight incubation.

PMID- 1366379
TI  - Enumerating low densities of genetically engineered Erwinia carotovora in soil.
AB  - An inexpensive, quantitative, and sensitive technique was developed for detection
      of genetically engineered Erwinia carotovora in soil samples. Enrichment media,
      antibiotic resistance, and most probable number (MPN) analysis were used to
      enumerate as few as 1 to 10 target cells/10 g soil. The MPN technique recovered
      significantly higher cell densities than plating; however, densities estimated by
      the two techniques were strongly correlated. After inoculation of soil microcosms
      with genetically engineered E. carotovora, a decline rate of 1.2 log units/g
      soil/10 days and then subsequent disappearance was observed using the MPN
      technique.

PMID- 1366380
TI  - Oxygen derepresses deacetoxycephalosporin C synthase and increases the conversion
      of penicillin N to cephamycin C in Streptomyces clavuligerus.
AB  - When dissolved oxygen (DO) was maintained at saturation level during batch
      fermentations of Streptomyces clavuligerus (NRRL 3585), the accumulation of the
      intermediate penicillin N was lowered while formation of the end product
      cephamycin C was increased relative to fermentations without DO control. The
      specific activity of the penicillin ring-expansion enzyme deacetoxycephalosporin
      C synthase (DAOCS) was increased 2.3-fold under oxygen saturated conditions,
      whereas the penicillin ring-cyclizing enzyme isopenicillin N synthase (IPNS)
      showed only a 1.3-fold increase. Thus oxygen derepression of DAOCS appears to be
      an important regulatory mechanism in the conversion of penicillin N to cephamycin
      C in S. clavuligerus. IPNS, an early acting enzyme in cephamycin C biosynthesis,
      and DAOCS, which acts late in the pathway, both disappeared from cell extracts at
      60 h, just prior to cessation of cephamycin production.

PMID- 1366381
TI  - Ultrafiltration membranes as carriers for lipase immobilization.
AB  - The feasibility of directly incorporating lipase from Rhizopus in the interior of
      poly(vinyl chloride) ultrafiltration membranes during the phase inversion process
      for their manufacturing has been demonstrated. The obtained membranes used for
      plant oil hydrolysis have shown better time stability as compared with those of
      lipase immobilized by adsorption. The specific activity of entrapped lipase
      achieves values higher than those of the soluble one. The activity of immobilized
      lipase is strongly affected by the rate of removing fatty acids from the interior
      of the membrane.

PMID- 1366382
TI  - Papain-catalysed synthesis of dipeptides: a novel approach using free amino acids
      as nucleophiles.
AB  - For the first time, papain-catalysed synthesis of peptide bonds was successfully
      carried out using free amino acids as nucleophiles. In kinetically controlled
      experiments employing pH-Stat-mode, the ester substrates Z-Ala-OMe and Z-Gly-OMe
      were coupled with alanine, glutamine, and Cys(Acm)-OH, respectively. Under
      optimized reaction conditions (pH 9.2, high ratio nucleophile/carboxyl component,
      10 mumol substrate mg-1 papain), the peptide yields ranged from 17% to 79%,
      depending on the structure of the amino and/or carboxyl component. The peptides
      formed were not hydrolysed under the chosen reaction conditions. With Z-Gly-OMe
      as the ester substrate, formation of the dipeptide was both rapid and high
      yielding. Papain-catalysed formation of peptide bonds applying free amino acids
      as nucleophiles might serve as an economic and easily manageable approach for the
      synthesis of short-chain peptides to be used in clinical nutrition.

PMID- 1366383
TI  - Enhancement of cyclosporin production in a Tolypocladium inflatum strain after
      epichlorohydrin treatment.
AB  - Following treatment of conidia of the cyclosporin producer fungus, Tolypocladium
      inflatum, with 0.15 M epichlorohydrin, strain M6 was isolated. The new strain
      exhibited a similar growth rate to the parent organism but more extensive
      conidiation and several-fold higher overall cyclosporin production. Strain M6
      reached titres of 318 mg l-1 cyclosporin A in agar cultures, whereas in liquid
      medium it produced 140 mg l-1 cyclosporin A and 68 mg l-1 cyclosporin C. It also
      maintained a steady volumetric productivity of 0.48 mg l-1 h-1 cyclosporin A over
      2 weeks of submerged cultivation in maltose-based semisynthetic medium. The new
      strain holds potential for improved cyclosporin production due to the superior
      titres and demonstrated capacity to sustain elevated production of cyclosporin
      for periods greater than the wild type.

PMID- 1366384
TI  - Synthesis and biological activity of some new 2-chlorophenothiazine derivatives.
AB  - 10-(Hetero/arylthio)acetyl-2-chlorophenothiazines II have been synthesized via
      interaction of 10-chloroacetyl-2-chlorophenothiazine I with heterocyclic and/or
      aromatic potassium mercaptide in ethanol. Oxidation of II using H2O2/CH3COOH
      mixture was studied. Structures of the products were verified by elemental and
      spectral analyses. Some compounds were screened in vitro for their antibacterial
      activities.

PMID- 1366385
TI  - Landfill co-disposal of phenol-bearing wastewaters: organic load considerations.
AB  - A multi-stage model, operated with single elution, was used to investigate the
      effects of organic loadings on the attenuation of a model phenolic wastewater in
      domestic refuse. Although 100% dissimilation of influent phenol (2-5 mmol dm-3)
      was recorded at a dilution rate of 0.007 h-1, partial inhibition of both phenol
      degradation and species competing with methanogens for a common electron donor(s)
      was apparent at concentrations greater than or equal to 4 mmol dm-3. On extended
      perfusion with 8 mmol phenol dm-3, the progressive inhibition of phenol
      dissimilation was not obviated by nutrient supplementation. Simultaneous
      degradation of the catabolic intermediate, hexanoic acid, and elevated methane
      release rates suggested that the transformation of phenol to hexanoate was rate
      limiting.

PMID- 1366386
TI  - Mass spectral characterization of acyloxymethyl phosphates.
AB  - A series of organophosphates having one or two acyloxymethyl groups have been
      characterized by methane chemical ionization mass spectrometry: twelve are model
      compounds with phenyl and benzyl groups while four are derived from pyrimidine-3'
      deoxyriboside-5'-monophosphates. Some are protonated cyclohexyl-ammonium salts.
      In addition the phenyl and benzyl phosphate spectra exhibit an abundance of
      fragmentation and rearrangement ions, the majority of which were products of
      three processes--expulsion of formaldehyde, loss of the acyloxymethyl group with
      transfer of hydrogen to the phosphate, and fission of the methylene-acyloxy bond.
      The pyrimidine-3'-deoxyriboside-5'-monophosphate esters give less fragmentation
      under similar circumstances; prominent ions in their spectra are the protonated
      molecular ions and losses of one and two molecules of formaldehyde from them and
      the protonated bases.

PMID- 1366387
TI  - Production, thermal stability and immobilisation of inulinase from Fusarium
      oxysporum.
AB  - Fusarium oxysporum produced maximum extracellular inulinase after 9 days of its
      growth at 25 degrees C on a medium (pH 5.5) containing 3% fructan and 0.2% sodium
      nitrate. The level of this enzyme decreased on the addition of either glucose,
      fructose, galactose or sucrose to F. oxysporum already growing on a fructan
      containing medium. A significant increase in invertase production which resulted
      in an increase of the invertase/inulinase (S/I) ratio, was observed on addition
      of inulin to this fungus growing on other carbon sources. Glycerol (10%) gave
      better protection to inulinase against thermal denaturation at 50 degrees C
      compared to ethylene glycol and sorbitol. Inulinase immobilised in polyacrylamide
      gel retained 45% of its original activity. The immobilised enzyme showed a higher
      optimum temperature (45 degrees C) compared to free enzyme (37 degrees C). The
      immobilised enzyme after storage at 25 degrees C for 96 h showed 58% activity.
      Thermal stability of entrapped inulinase increased in the presence of inulin.

PMID- 1366388
TI  - Comparison of oxygen supply methods for cultures of shear-stress sensitive
      organisms including animal cell culture.
AB  - In animal cell culture, oxygen supply sometimes limits cell growth. Therefore,
      four oxygen supply methods (free surface aeration, porous Teflon tubing,
      perfluorocarbon addition and external aerator) were compared in terms of oxygen
      transfer rate for suspension culture of animal cells. Oxygen transfer rate with
      the free surface aeration was dependent on the vertical position of the impeller
      and the stirred Reynolds number for h/HL greater than 0.35, but no effect of the
      impeller position was observed for h/HL less than 0.35. The relationship between
      the Reynolds and Sherwood numbers could be expressed by simple correlations.
      These correlations could also be applied to oxygen transfer using porous Teflon
      tubing. When oxygen was supplied with perfluorocarbon saturated with air, the
      overall mass transfer coefficient KL was estimated to be about 9.0 X 10(-3) cm s
      1, which was five-fold greater than that of the surface aeration. Maximum cell
      densities which would be supported by four methods were calculated from values of
      KLa for different sizes of fermentor assuming that oxygen supply would be the
      rate-limiting factor in animal cell culture.

PMID- 1366389
TI  - Biotransformation of alkyl and aryl carbonates. Microbial degradation.
AB  - An enriched mixed culture was successfully grown on model alkyl and aryl
      carbonates. These compounds were degraded by microorganisms at different rates. P
      Chlorophenyl-2-octyl carbonate and p-nitrobenzyl-2-octyl carbonate were
      metabolized through the formation of p-chlorophenol and p-nitrobenzyl alcohol
      respectively. A strain of Acinetobacter calcoaceticus isolated from the mixed
      culture utilized phenyl-2-octyl carbonate by an intracellular hydrolase to phenol
      and 2-octanol which were further metabolized.

PMID- 1366390
TI  - Genetic complementation of Streptomyces tendae deficient in nikkomycin
      production.
AB  - Streptomyces tendae Tu 901 produces the nucleoside peptide antibiotic nikkomycin.
      In shot-gun cloning experiments using pIJ699 as vector we isolated a 9.4-kb DNA
      fragment from S. tendae which complemented the nikkomycin nonproducing mutant NP9
      to the formation of nikkomycin C/Cx and Kx. Nikkomycins were identified by HPLC
      analyses and their characteristic UV spectra. In Southern hybridization
      experiments the cloned DNA exclusively reacted with S. tendae DNA sequences. As
      shown by Northern dot blotting, transcripts of the isolated DNA fragment were
      only detected during stationary growth and correlated with the extent of
      nikkomycin production. When the recombinant plasmid pNP113 containing the 9.4-kb
      DNA fragment was transferred into the over-producing mutant Tu901/S2566,
      transformants exhibited a significantly decreased capacity for forming
      nikkomycin. Southern analysis of genomic DNA of these transformants revealed that
      severe rearrangements occurred in DNA sequences homologous to the 9.4-kb insert
      of pNP113.

PMID- 1366391
TI  - Optimum conditions for efficient transformation of Streptomyces venezuelae
      protoplasts.
AB  - Optimum conditions for protoplast regeneration and transformation of Streptomyces
      venezuelae ETH14630 have been established. Protoplasts from mycelium grown to the
      stationary phase and treated with lysozyme in P medium under mild conditions gave
      the best regeneration frequency. Transformation of protoplasts with naked DNA was
      very efficient using either polyethylene glycol of mol. wt. 4000 or 6000, at
      concentrations of 28.5% or 36% (w/v) respectively. About 10(7)
      transformants/micrograms DNA could be isolated using protoplasts derived from
      cells cultivated to the early exponential growth phase in LB medium containing
      0.2%-0.6% glycine and subsequently treated at 30 degrees -32 degrees C with 20 mg
      lysozyme/ml in P medium for 30 min. Selection of the transformants occurred on
      MRYE plates containing less than 10(5) regenerating protoplasts per plate. Higher
      protoplasts densities considerably decreased the regeneration frequency of the
      transformants.

PMID- 1366392
TI  - Screening of basidiomycetes for lignin peroxidase genes using a DNA probe.
AB  - Basidiomycetes were screened for lignin peroxidase (LPO) genes using a DNA probe
      prepared from the LPO restriction fragment of Phanerochaete chrysosporium.
      Southern blot analysis showed restriction fragments of chromosomal DNA of
      Bjerkandera adusta and Coriolus consors hybridized with the probe. Bjerkandera
      adusta produced LPO in a glucose-peptone medium. Ion-exchange chromatography
      showed that this fungus produced multiple molecular forms of LPO. One of the
      enzymes, LPO-2, was purified and characterized. The molecular weight of LPO-2 was
      41,000 with a pI of 4.2. Spectral analysis demonstrated that LPO-2 is a haem
      protein. The enzyme cleaved lignin model dimers mainly at the C alpha-C beta
      position of the side chain. The LPO-2 exhibited close similarity to LPOs of P.
      chrysosporium with respect to their basic properties.

PMID- 1366393
TI  - Cloning of a DNA fragment from Corynebacterium glutamicum conferring aminoethyl
      cysteine resistance and feedback resistance to aspartokinase.
AB  - The Corynebacterium glutamicum/Escherichia coli shuttle vector plasmid pZ1 was
      used to clone the S-(2-aminoethyl)-D,L-cysteine (AEC)-resistance gene from a
      lysine-excreting, AEC-resistant strain of C. glutamicum, the aspartokinase
      activity of which was released from feedback inhibition by mixtures of lysine and
      threonine or AEC and threonine respectively. A recombinant plasmid designated
      pCS2 carrying a 9.9-kb chromosomal insert that conferred AEC resistance and the
      ability to excrete lysine to its host was isolated. The aspartokinase activity of
      the pCS2-carrying strain was resistant towards inhibition by mixtures of lysine
      and threonine or AEC and threonine respectively. By deletion analysis the DNA
      region conferring AEC resistance to the host and feedback resistance to its
      aspartokinase activity could be confined to a 1.2-kb DNA fragment.

PMID- 1366394
TI  - Nutritional control of actinorhodin production by Streptomyces coelicolor A3(2):
      suppressive effects of nitrogen and phosphate.
AB  - Actinorhodin production in Streptomyces coelicolor A3(2) was relatively
      insensitive to the carbon source concentration but was elicited by nitrogen or
      phosphate depletion, or by a decline in the growth rate. In starch-glutamate
      media with nitrogen limitation, increasing the nitrogen supply delayed the onset
      of antibiotic synthesis and, at concentrations above 30 mM, decreased its rate.
      In a similar medium with phosphate limitation, increasing the initial phosphate
      concentration delayed actinorhodin formation and, above 2.5 mM, reduced the rate
      of synthesis. Experiments in which actinorhodin synthesis was elicited by
      phosphate depletion at various nitrogen concentrations demonstrated strong
      suppression by residual glutamate. Cultures in which actinorhodin biosynthesis
      was initiated by nitrogen depletion were not similarly suppressed by increasing
      amounts of residual phosphate. The results suggest that actinorhodin production
      in S. coelicolor A3(2) responds to interacting physiological controls, notable
      among which is nitrogen catabolite regulation.

PMID- 1366396
TI  - Effect of the addition of microbial surfactants on hydrocarbon degradation in a
      soil population in a stirred reactor.
AB  - The hydrocarbon degradation rate could be doubled by the addition of sophorose
      lipids as biosurfactants in a model system containing 10% soil and a 1.35%
      hydrocarbon mixture of tetradecane, pentadecane, hexadecene, 1,2,4
      trimethylcyclohexane, pristane (2,6,10,14-tetramethylpentadecane) phenyldecane
      and naphthalene suspended in mineral salts medium. The adaptation phases for two
      degradation phases were shortened, and the extent of degradation and final
      biomass were increased. The added biosurfactants were degraded after they had
      facilitated degradation of all hydrocarbon components.

PMID- 1366395
TI  - Degradation of phenanthrene, fluorene and fluoranthene by pure bacterial
      cultures.
AB  - Bacterial mixed cultures able to degrade the polycyclic aromatic hydrocarbons
      (PAH) phenanthrene, fluorene and fluoranthene, were obtained from soil using
      conventional enrichment techniques. From these mixed cultures three pure strains
      were isolated: Pseudomonas paucimobilis degrading phenanthrene; P. vesicularis
      degrading fluorene and Alcaligenes denitrificans degrading fluoranthene. The
      maximum rates of PAH degradation ranged from 1.0 mg phenanthrene/ml per day to
      0.3 mg fluoranthene/ml per day at doubling times of 12 h to 35 h for growth on
      PAH as sole carbon source. The protein yield during PAH degradation was about
      0.25 mg/mg C for all strains. Maximum PAH oxidation rates and optimum specific
      bacterial growth were obtained near pH 7.0 and 30 degrees C. After growth entered
      the stationary phase, no dead end-products of PAH degradation could be detected
      in the culture fluid.

PMID- 1366398
TI  - An optimistic view of biotechnology.

PMID- 1366397
TI  - In vitro human tumor sensitivity assay using cell counting and sizing.

PMID- 1366399
TI  - Advances in cDNA technology.

PMID- 1366400
TI  - Analyzing organic molecules with electrospray mass spectrometry.

PMID- 1366401
TI  - Weak affinity chromatography: a new tool for immunoassays.

PMID- 1366402
TI  - Molecular biology in 2001.

PMID- 1366403
TI  - Survey and opinions: barriers to field-testing genetically modified organisms.

PMID- 1366404
TI  - Production of correctly processed human serum albumin in transgenic plants.
AB  - We have used a modified CaMV 35S promoter to direct the expression of chimaeric
      genes encoding human serum albumin (HSA) in transgenic potato and tobacco plants.
      To secrete the protein, either the human prepro-sequence or the signal sequence
      from the extracellular tobacco protein PR-S was used. We demonstrate secretion of
      HSA with both types of signal sequences in transgenic leaf tissue and in
      suspension cultures. HSA produced in transgenic potato plants was purified to
      chromatographic homogeneity. N-terminal amino acid sequence analysis revealed
      that the processing of the precursor protein was dependent on the type of signal
      sequence. Expression of the human preproHSA gene lead to partial processing of
      the precursor and secretion of proHSA. Fusion of HSA to the plant PR-S
      presequence resulted in cleavage of the presequence at its natural site and
      secretion of correctly processed HSA that is indistinguishable from the authentic
      human protein.

PMID- 1366405
TI  - Regulation of isopenicillin N synthetase (IPNS) gene expression in Acremonium
      chrysogenum.
AB  - Total RNA was extracted daily from the beta-lactam antibiotic producing fungus A.
      chrysogenum strain CO728 during a 7 day cephalosporin C fermentation. IPNS mRNA
      species, with a size of about 1.5 kb, were detected by Northern blotting at high
      levels between days 2 and 4. The rapid appearance of IPNS mRNA in mycelial
      extracts up to day 2 suggests that IPNS is regulated at the transcriptional
      level. Primer extension and S1 endonuclease mapping studies indicate the
      existence of two major and at least two minor transcription initiation start
      sites. There was no change in the relative levels of the four transcripts during
      the period they could be detected. A region upstream of the IPNS structural gene
      (pcbC) has been sequenced and the transcription initiation sites appear as major
      and minor pairs on either side of one of the pyrimidine-rich blocks that
      punctuate the promoter sequence.

PMID- 1366406
TI  - Support for biotechnology.

PMID- 1366407
TI  - An investigation of engineering parameters for the use of immobilized biomass
      particles in biosorption.
AB  - Immobilized, inactive mycelia of Rhizopus arrhizus are preferential to native
      biomass for use in the biosorption of metal ions. Refinement of a proprietary
      immobilization technique previously developed at McMaster University enabled
      production of particles of immobilized Rhizopus arrhizus biomass having a 12-23%
      wt of polymer additive. The effects of production stage parameters on the
      intrinsic uptake capacity of the immobilized biomass were examined. Kinetic
      experiments showed the following trends: a decrease in the weight percent of the
      added polymer leads to an increase in the apparent uranium uptake capacity of the
      immobilized biomass particles for a given contact time. A decrease in the
      particle size improved the kinetics of metal uptake and led to an increase in the
      apparent uranium uptake capacity for the same contact time. An increase in the
      initial concentration of the uranium solution caused equilibrium conditions to be
      attained faster.

PMID- 1366408
TI  - Biomass production by a thermotolerant yeast: Hansenula polymorpha.
AB  - Biomass production at high temperature by Hansenula polymorpha as part of a
      lignocellulosic utilizing process was studied. Compromise growth conditions (45
      degrees C and pH = 4.8) with an eventual saccharification step were established.
      The effects of stirring rate and initial glucose concentration on biomass yield
      coefficient, volumetric productivity and maximal cell density were determined.
      Process optimization led to a fed-batch fermentation process: high yield (0.63 g
      dry cell g-1 glucose), volumetric productivity (1.3 g dry cell dm-3 h-1) and cell
      concentration (60 g dry cell dm-3) were obtained. At these conditions,
      significant arabitol excretion (18 g dm-3) as a unique by-product associated with
      cell mass production was obtained, making more interesting a high temperature
      operating process.

PMID- 1366409
TI  - Effect of diffusional resistances on the action pattern of immobilized alpha
      amylase.
AB  - Alpha-amylase from Aspergillus oryzae has been immobilized onto corn grits and
      porous silica (specific areas 180 and 440 m2 g-1). Kinetic parameters of
      immobilized enzyme have been determined. Immobilization of alpha-amylase results
      in the formation of less polymerized products resulting in an apparent decrease
      in the number of transglycosylation reactions, for both maltotetraose and starch
      as substrates, when compared with free enzyme. Diffusional limitations for
      substrate and products have been quantified in the case of the three supports
      used. External diffusional resistances were important in all cases for the
      reaction products, whilst they became negligible for the substrate in the case of
      silica supports. Moreover, internal transfer limitations were identified with
      silica 180 m2 g-1 support. It was demonstrated that diffusional resistances were
      in direct relation to the apparent modification of the enzyme action pattern
      after immobilization.

PMID- 1366410
TI  - Factors influencing the activity and thermostability of immobilized porcine
      pancreatic lipase.
AB  - Lipase from porcine pancreas was immobilized on cellulose beads having various
      degrees of hydrophobicity, by covalent linking and by hydrophobic adsorption.
      Lipolytic activity was measured in heterogeneous organic-aqueous systems of
      various hydrophobicities using olive oil as a substrate. The main factors
      influencing lipase activity were hydrophobicity of the reaction mixture and of
      the carrier. Carriers with increased hydrophobicity enhanced lipase activity more
      than less hydrophobic ones. Lipase immobilized covalently on cellulose beads was
      less active than that adsorbed onto tritylcellulose but was considerably more
      thermostable.

PMID- 1366411
TI  - Automated image analysis: there has to be a better way.

PMID- 1366412
TI  - Video enhancement and image processing in light microscopy. Part 3: Display
      processing.

PMID- 1366413
TI  - Applications of magnetic separation: cell sorting.

PMID- 1366414
TI  - Equipping a micromanipulation workstation.

PMID- 1366415
TI  - The human genome project: prospects and politics.

PMID- 1366416
TI  - Metabolic activation in isolated rat hepatocytes.
AB  - Hepatocytes were exposed in vitro to the hepatocarcinogen N-hydroxy-2
      aminofluorene (N-OH-AAF) in order to determine the nature and repair of DNA
      adducts formed. N-OH-AAF formed 3 DNA adducts, N-(deoxyguanosin-8yl)-2
      acetylaminofluorene (dG-C8-AAF), N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8
      AF), and 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene (dG-N2-AAF). The removal
      of these adducts was measured up to 38 h following cessation of exposure to N-OH
      AAF. The dG-C8-AAF adduct was removed with a half-life of about 10 h, while the
      other two remained relatively constant throughout the incubation period. The dG
      C8-AAF adduct is probably responsible for the induction of unscheduled DNA
      synthesis (UDS) in this model in vitro system.

PMID- 1366417
TI  - Natural transformation in Acinetobacter calcoaceticus.
AB  - Acinetobacter calcoaceticus is a metabolically versatile microorganism that is
      naturally competent for DNA uptake and incorporation. We have exploited the
      natural state of competency for studies involving the cloning, organization and
      expression of genes encoding catabolic enzymes. A. calcoaceticus is able to take
      up, at high efficiency, genetically engineered DNA, incorporate the DNA and
      stably maintain and express the DNA. Sequence analysis of cloned A. calcoaceticus
      DNA reveals a great deal of internal repetition and secondary structure, but no
      specific sequences associated with uptake appear to be present. Uptake and
      transformation occurs in solid and liquid medium, at a wide range of DNA
      concentrations and with little restriction barrier to the source of the
      transforming DNA.

PMID- 1366418
TI  - The recombinant human parvoviruses for gene therapy of hemoglobinopathies.
AB  - Towards a goal of using adeno-associated viruses (AAV), the human parvovirus, as
      the gene transfer vector for gene therapy of hemoglobinopathies, the human beta
      globin (h beta G) cDNA was ligated downstream of the P40 promoter of AAV type 2
      (AAV2) genome. Transfection via electroporation of the construct into human 293
      cells (embryonal kidney cell line) resulted in expression of the cloned h beta G
      cDNA, as evidenced by the synthesis of transcripts hybridizable to h beta G
      probe. The transfection led to the recombinant genome to be excised out of the
      plasmid and replicate in the cell, followed by production of the recombinant AAV
      that harbors h beta G cDNA.

PMID- 1366419
TI  - Intramolecular thiolester linkages in apolipoprotein B.
AB  - Intramolecular thiolester bonds in apolipoprotein B (ApoB) were studied using
      [14C]methylamine (MA) to cleave the thiolester and [3H]- or [14C]iodoacetate (IA)
      to titrate the newly generated sulfhydryls. Covalent incorporation of [14C]MA and
      [3H]carboxylmethyl group into the previously carboxymethylated LDL or the reduced
      and carboxymethylated ApoB was observed and both radioactivities coincided with
      ApoB-100 band on SDS-polyacrylamide gel electrophoresis. The [14C]MA-labeled ApoB
      was completely trypsinized and cross-linked to the activated thiol Sepharose 4B
      beads. The peptides were eluted with DTT and the free -SH groups blocked with IA
      then separated on FPLC. Two fractions contained [14C]MA. Sequence analyses showed
      that these labeled peptides contained Cys-51 and Cys-3734, respectively. Evidence
      suggests that the thiolester is formed between Cys-51 and gamma-Glu-54 for one,
      and Cys-3734 and beta-Asp-3737 for the other, with Lys and a hydrophobic amino
      acid, Val/Leu, in between. This is the first evidence for the presence of
      intramolecular thiolester linkages in ApoB. The presence of high energy, labile
      thiolester bonds may explain many of the unusual properties of ApoB and LDL.

PMID- 1366420
TI  - Expression of chimeric human transferrin genes in transfected human tumor cell
      lines.
AB  - The iron-binding plasma protein transferrin (TF) is essential for supplying iron
      to cells and the prevention of iron toxicity. Our laboratory has cloned and
      characterized the human TF gene. Comparison of promoter regions of TF genes from
      human, chicken, and mouse reveals a strong nucleotide sequence conservation. This
      study demonstrates that 5' flanking regions of the TF gene are sufficient for
      directing expression of a heterologous gene in transgenic mice and transfected
      cells. For cell-specific expression, more than 150 base pairs appear to be
      required.

PMID- 1366421
TI  - The pursuit of pain.

PMID- 1366422
TI  - Determination of oxygen profiles in biocatalyst particles by means of a combined
      polarographic oxygen microsensor.
AB  - When studying the effect of immobilization of enzymes or whole cells on the
      conversion of substrate, more information is gained if measurements of substrate
      inside the biocatalyst particles are possible. With the methods used until now,
      only measurements outside the particle can be performed. In this article a method
      for measuring oxygen profiles in a biocatalyst particle under steady state
      conditions is described. The biocatalyst particle was made of agarose and
      contained the enzyme L-lactate 2-monooxygenase. This enzyme decarboxylates lactic
      acid to acetic acid in the presence of oxygen. The experiments were carried out
      in a flow chamber with the use of a micromanipulator and a stereomicroscope. The
      data were sampled by means of a computer. Four different profiles were measured
      using four different enzyme concentrations. The measured oxygen profiles were
      reproducible and the signal was very stable. It was also possible to measure the
      boundary layer around the particle. With the use of the oxygen microsensor,
      measurements in a biocatalyst particle could be performed accurately, giving way
      for model validation.

PMID- 1366423
TI  - Cloning and expression of a lignin peroxidase gene from Streptomyces viridosporus
      in Streptomyces lividans.
AB  - A lignin peroxidase gene was cloned from Streptomyces viridosporus T7A into
      Streptomyces lividans TK64 in plasmid pIJ702. BglII-digested genomic DNA (4-10
      kb) of S. viridosporus was shotgun-cloned into S. lividans after insertion into
      the melanin (mel+) gene of pIJ702. Transformants expressing pIJ702 with insert
      DNA were selected based upon the appearance of thiostrepton resistant (tsrr)/mel
      colonies on regeneration medium. Lignin peroxidase-expressing clones were
      isolated from this population by screening of transformants on a tsr-poly B-411
      dye agar medium. In the presence of H2O2 excreted by S. lividans, colonies of
      lignin peroxidase-expressing clones decolorized the dye. Among 1000 transformants
      screened, 2 dye-decolorizing clones were found. One, pIJ702/TK64.1 (TK64.1), was
      further characterized. TK64.1 expressed significant extracellular 2,4
      dichlorophenol (2.4-DCP) peroxidase activity (= assay for S. viridosporus lignin
      peroxidase). Under the cultural conditions employed, plasmidless S. lividans TK64
      had a low background level of 2.4-DCP oxidizing activity. TK64.1 excreted an
      extracellular peroxidase not observed in S. lividans TK64, but similar to S.
      viridosporus lignin peroxidase ALip-P3, as shown by activity stain assays on
      nondenaturing polyacrylamide gels. The gene was located on a 4 kb fragment of S.
      viridosporus genomic DNA. When peroxidase-encoding plasmid, pIJ702.LP, was
      purified and used to transform three different S. lividans strains (TK64, TK23,
      TK24), all transformants tested decolorized poly B-411. When grown on
      lignocellulose in solid state processes, genetically engineered S. lividans
      TK64.1 degraded the lignocellulose slightly better than did S. lividans TK64.
      This is the first report of the cloning of a bacterial gene coding for a lignin
      degrading enzyme.

PMID- 1366424
TI  - New monoclonal antibodies to 3 beta-hydroxy-gibberellins.
AB  - Two new monoclonal antibodies to 3 beta-hydroxy-gibberellins are described.
      Monoclonal antibodies GA1-1 and GA1-2 were derived from immunizations with the
      hapten-protein conjugate gibberellin A1-17-KLH. Cross-reactivities with a panel
      of 43 gibberellins and gibberellin derivatives are compared with those of other
      anti-gibberellin monoclonal antibodies.

PMID- 1366425
TI  - Induction of two prenyltransferases for the accumulation of coumarin phytoalexins
      in elicitor-treated Ammi majus cell suspension cultures.
AB  - Two dimethylallyl diphosphate:umbelliferone dimethylallyltransferase
      (prenyltransferase) activities, catalysing the 6-prenylation and the 7-O
      prenylation, respectively, of umbelliferone in the course of phytoalexin
      synthesis, increased in Ammi majus cell suspension cultures in response to
      elicitor treatment. Both enzyme activities were dependent on Mg2+ or Mn2+ with
      significant preference for Mg2+ in the 6-prenylation reaction. Whereas dark-grown
      cells did not contain these activities, both prenyltransferase activities were
      induced rapidly by the addition of elicitor reaching a first maximum after 10-14
      hr and a second maximum beyond 30 hr. Other coumarin specific, elicitor-induced
      enzyme activities of A. majus cells, in contrast, showed only one maximum of
      activity within the 50 hr experimental period, while the pattern of induction of
      phenylalanine ammonia-lyase activity resembled that of the prenyltransferases
      with maxima at ca 8 hr and 20-30 hr. Preliminary data suggest that the apparent
      biphasic induction of these enzyme activities is due to post-translational enzyme
      modifications.

PMID- 1366426
TI  - Composition of the gum from Combretum paniculatum and four other gums which are
      not permitted food additives.
AB  - Only three gum exudates are permitted for pharmaceutical and food use by
      international regulatory authorities, viz. gum tragacanth (Asiatic Astragalus
      spp.), gum karaya (Sterculia spp.) and gum arabic [Acacia senegal (L.) Willd.],
      but a wide range of other tree exudates is used for a variety of uses in their
      countries of origin. This paper presents analytical data for the gum exudates
      from Atalaya hemiglauca, Cassine aethiopica, Combretum paniculatum, Sclerocarya
      birrea, and Pseudocedrela kotschyi. These gums may have local technological
      applications, but are not recommended for addition to foodstuffs.

PMID- 1366427
TI  - Phlinosides A, B and C, three phenylpropanoid glycosides from Phlomis linearis.
AB  - Three new phenylpropanoid glycosides, phlinosides A, B and C were isolated from a
      methanolic extract of the aerial parts of Phlomis linearis. On the basis of
      chemical and spectral evidence their structures were determined as 3,4-dihydroxy
      beta-phenylethoxy-O-beta-D-glucopyranosyl-(1----2)-a lpha-L- rhamnopyranosyl-(1--
      -3)-4-O-caffeoyl-beta-D-glucopyranoside, 3,4 dihydroxy-beta-phenylethoxy-O-beta-D
      xylopyranosyl-(1----2)-alpha- L- rhamnopyranosyl-(1----3)-4-O-caffeoyl-beta-D
      glucopyranoside and 3,4-dihydroxy-beta-phenylethoxy-O-alpha-L-rhamnopyranosyl-(1-
      --2) -alpha- L-rhamnopyranosyl-(1----3)-4-O-caffeoyl-beta-D-glucopyranoside,
      respectively.

PMID- 1366428
TI  - Two flavonol glycosides from the underground parts of Vancouveria hexandra.
AB  - Two new flavonol glycosides were isolated from the roots and rhizomes of
      Vancouveria hexandra. The glycosides were determined by chemical and spectral
      means to be anhydroicaritin 3-galactosyl(1----3) rhamnoside-7-glucoside and
      anhydroicaritin 3-[6-O-acetyl-galactosyl(1----3)rhamnoside]-7-glucoside.

PMID- 1366429
TI  - Flavonol triglycosides from Blackstonia peroliata.
AB  - Three new flavonol triglycosides quercetin, kaempferol and isorhamnetin 3
      rhamnosyl(1----2)galactoside-7-glucosides have been isolated from leaves and
      stems of Blackstonia perfoliata. This species together with three other genera of
      the tribe Gentianeae, subtribe Chlorae: Centaurium, Coutoubea and Eustoma, is
      unusual in producing flavonol glycosides instead of C-glycosyl flavones, the more
      characteristic flavonoid constituents of the Gentianaceae.

PMID- 1366430
TI  - An indole derivative and glucosinolates from Moricandia arvensis.

PMID- 1366431
TI  - An acylated isorhamnetin glycoside from Aerva javanica.

PMID- 1366432
TI  - Flavonol diglycosides from Blackstonia perfoliata.
AB  - Two unusual diglycosides, quercetin and kaempferol 3-rhamnosyl(1---
      2)galactosides and the new isorhamnetin 3-rhamnosyl(1----2)galactoside have been
      isolated from the aerial parts of Blackstonia perfoliata. Instead of C
      glycosylflavones, the occurrence of flavonol glycosides in this species as well
      as in three other genera of the Gentianaceae: Centaurium, Coutoubea and Eustoma,
      is in agreement with the grouping of these four genera in the subtribe Chlorae of
      the Gentianeae.

PMID- 1366433
TI  - Chitosan-poly(acrylic acid): mechanism of complex formation and potential
      industrial applications.
AB  - The food industry is interested in polyelectrolytic coagulants of natural origin
      for the clarification of food beverages and the recovery of colloidal and
      dispersed particles from processing waste streams. This paper discusses potential
      industrial applications of recent findings on polymer complex formation obtained
      with a chitosan-poly(acrylic acid) model system. Process recommendations could be
      made on the basis of the ionic strength, pH, and charged group concentration of
      the fluid to be treated. Ionic strength does not affect the complex formation
      process. The amount of chitosan in the complex formed is controlled by the
      solution pH. The mechanism of complex formation indicates that pH measurements
      could be used to monitor the coagulation process.

PMID- 1366434
TI  - Effects of sterilization treatments on some properties of alginate solutions and
      gels.
AB  - Aqueous sodium alginate solutions were subjected to various heat sterilization
      treatments. Sodium alginate powder was also treated by both gamma-irradiation and
      ethylene oxide sterilization. The effects of these treatments on the viscosities
      of sodium alginate solutions and both the diameter and strength of the beads
      formed in 0.1 M CaCl2 solutions were determined quantitatively. The viscosity of
      sodium alginate solutions and the gel strength of the calcium alginate beads
      decreased with increasing sterilization temperature while the bead diameters were
      found to increase. All these effects can be attributable to a reduction in the
      degree of polymerization of the alginate molecules as a result of the heat
      treatments. Ethylene oxide and gamma-irradiation treatments caused similar
      effects. Standard conditions for sterilization are necessary for comparative
      studies with alginate beads.

PMID- 1366435
TI  - Experimental collision efficiencies of polymer-flocculated animal cells.
AB  - The determination of particle collision kinetics is useful to decouple the
      effects of process parameters on individual events in flocculation. This paper
      discusses the effects of flocculation conditions on the collision efficiency of
      ATCC strain CRL 1606 hybridomas flocculated with poly-L-histidine. Experimental
      determinations of the collision efficiency of cells in Couette flow are presented
      over a range of experimental conditions. The collision efficiency correlates with
      the cell zeta potential to the -2.4 power at high surface coverage, consistent
      with literature results in latex systems. At low coverage, accounting for the
      distribution of polymer on the cells corrects for deviation from the high
      coverage behavior. Collision is dependent on the hydrodynamic environment as
      well. At high surface coverage, collision efficiency is weakly dependent on
      hydrodynamic conditions and follows a dependency on the shear rate and viscosity
      to the -0.32 power. This is consistent with ionic coagulation theory. At low
      surface coverage, the collision efficiency is strongly dependent on the viscous
      fluid forces. The results versus both dose and shear rate over the entire range
      of surface coverages are consistent with weak intercell bonding. Collision
      kinetics in the presence of high molecular weight dextrans show steric hindrance
      to cell collision.

PMID- 1366436
TI  - Two-barrel bile-acids-sensitive microelectrodes based on liquid ion exchanger.
AB  - Several liquid membrane microelectrodes sensitive to bile acids (two barrel, tip
      diameter about 0.5 micron) are described. The results of different liquid ion
      exchangers such as Aliquat 336/decanol, trioctylmethylammonium/decanol,
      hexadecyltrimethylammonium/decanol, benzyldimethylhexadecylammonium/decanol,
      hexadecyltributylammonium/5% hexachlorobenzene + 0.5% bromoacetanilide in o
      dichlorobenzene are compared with each other, and the better one among them is
      the mixture of benzyldimethylhexadecylammonium cholate/decanol with
      hexadecyltributylammonium taurocholate/5% hexachlorobenzene + 0.5%
      bromoacetanilide in o-dichlorobenzene because of its quicker response time and
      low drift. The calibration curves, slopes, test limits, selective coefficients,
      drifts, and response times of the various bile-acids-sensitive microelectrodes in
      different calibration solutions were demonstrated and compared with each other.

PMID- 1366437
TI  - Comparative studies on the fermentative production of lantibiotics by
      staphylococci.
AB  - The production of the lanthionine-containing polypeptide antibiotics gallidermin
      from Staphylococcus gallinarum TU 3928 and pep 5 from S. epidermidis 5 is
      investigated with respect to regulation and stimulation of productivity by media
      components, optimization of both the media used and the fermentation process and
      is compared to the production of the lantibiotic epidermin from S. epidermidis TU
      3298. Efficient methods for rapid quantification of lantibiotics, optimization of
      the media and a primary enrichment by adsorption chromatography are reported.

PMID- 1366438
TI  - Purification and characterization of acid urease from Lactobacillus fermentum.
AB  - Acid urease was purified to an electrophoretically homogeneous state, and the
      molecular weight was estimated to be 220,000. The enzyme consisted of three kinds
      of subunits, designated alpha, beta and gamma, with molecular weights of 67,000,
      16,800 and 8600, respectively, in a (alpha 1 beta 2 gamma 1)2 structure. The
      isoelectric point of the enzyme was 4.8. The nickel content was found to be 1.9
      atoms of nickel per alpha 1 beta 2 gamma 1 unit. The amino acid profile was
      different from those of known bacterial neutral ureases. The enzyme was most
      active at pH 2 and around 65 degrees C. It was stable between pH 3 and 9, and
      below 50 degrees C. The Km for urea was 2.7 mM at pH 2. The enzyme activity was
      inhibited by Ag+, Hg2+, Cu2+, p-chloromercuribenzoate and acetohydroxamate. The
      enzyme was separated into three subunits by reverse phase HPLC. The amino
      terminal amino acid sequences of the subunits alpha, beta and gamma were Ser-Phe
      Asp-Met-, Met-Val-Pro-Gly- and Met-Arg-Leu-Thr-, respectively.

PMID- 1366439
TI  - Mechanism of the stimulatory effect of cyclodextrins on lankacidin-producing
      Streptomyces.
AB  - Gel-filtration analysis of a mixture of cyclodextrin (CyD) and lankacidin C
      showed that beta-CyD had strong, gamma-CyD weak and alpha-CyD no affinity for
      lankacidin C. Lankacidin C production activity, which was assayed by measuring
      the incorporation of L-[methyl-14C-]methionine into the lankacidin molecule, was
      the greatest with cells grown in the presence of beta-CyD, less with gamma-CyD
      and the least with alpha-CyD. Lankamycin and T-2636M, which are by-products in
      lankacidin C fermentation, were not included by beta-CyD and their production was
      not stimulated by beta-CyD. It was apparent that the stimulatory effect of CyD
      was closely related to the formation of an inclusion complex between CyD and the
      antibiotic. Lankacidin C biosynthesis was repressed by preincubating cells with
      lankacidin C, while the repressive effect of lankacidin C was abrogated by the
      inclusion by beta-CyD. Thus, abrogation of feed-back repression seems to be a
      main mechanism of the effect of CyD. However, alpha-CyD, which had no affinity
      for lankacidin C, stimulated the production to the least extent and exhibited a
      complementary effect on the stimulation by beta-CyD or gamma-CyD, alpha-CyD also
      caused a change in cell morphology and cell-surface hydrophobicity. It was
      assumed that the modification of the cell surface is a secondary mechanism of the
      effect of CyD.

PMID- 1366440
TI  - Characterization and complementation of a cephalosporin-deficient mutant of
      Streptomyces clavuligerus NRRL 3585.
AB  - We have characterized a mutant of Streptomyces clavuligerus NRRL 3585 which is
      almost completely blocked in cephalosporin biosynthesis and exhibits depressed
      activities of both the delta(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV)
      synthetase and cyclase enzymes of the cephalosporin pathway. A wild-type DNA
      region was cloned which partially restores antibiotic production, ACV synthetase
      and cyclase activities to this mutant. The recombinant plasmid exhibits a
      variable copy number in different transformants. Hybridization experiments
      indicate that sequences homologous to the cloned region are present in various
      beta-lactam-producing Streptomyces spp. but absent in species which are not known
      to produce this class of antibiotics. Furthermore, the chromosomal copy of the
      cloned region lies in close proximity to a gene coding for the isopenicillin N
      synthase gene of the cephalosphorin pathway.

PMID- 1366441
TI  - Highly sensitive and fast detection of Phoma tracheiphila by polymerase chain
      reaction.
AB  - A new method for the diagnosis of the plant pathogenic fungus Phoma tracheiphila
      has been developed. The method takes advantage of the enzymatic amplification of
      a specific 102 bp-long target sequence of fungal DNA by the polymerase chain
      reaction (PCR) using Thermus aquaticus DNA polymerase. The amplified DNA was
      characterized by agarose-gel electrophoresis, molecular hybridization using a
      synthetic oligonucleotide probe and direct sequencing. The application of the new
      method makes possible fast and direct detection of the pathogen in lignified
      plant tissues, a goal not previously achieved when a cloned probe and a dot-blot
      test were employed. In addition the PCR test can be used to advantage as a
      particularly simple and fast way of typing fungal isolates. This is achieved by
      submitting to DNA amplification crude homogenates of fungal mycelium and
      analysing the amplified DNA on an agarose mini-gel.

PMID- 1366442
TI  - Bacterial metabolism of side-chain-fluorinated aromatics: unproductive meta
      cleavage of 3-trifluoromethylcatechol.
AB  - Sixteen bacterial strains capable of degrading alkylbenzenes and alkylphenols
      were directly isolated from soil and water. The degradation pathways are
      discussed. Alkylcatechols are almost exclusively cleaved via meta-ring fission.
      Meta-cleavage of 3-trifluoromethyl-(TFM)-catechol was observed with all strains
      at different rates although the reaction rates compared to catechol as a
      substrate varied considerably. All 2-hydroxy-6-oxohepta-2,4-dienoic acid
      hydrolases investigated showed strong binding of 7,7,7-trifluoro-2-hydroxy-6
      oxohepta-2,4-dienoic acid, the ring fission product of 3-TFM-catechol. Turnover
      rates, however, were negligible indicating this compound to be a general dead-end
      metabolite during metabolism of TFM-substituted compounds via meta-cleavage
      pathways.

PMID- 1366443
TI  - Correlation of biocatalytic activity in an organic-aqueous two-liquid phase
      system with solvent concentration in the cell membrane.
AB  - Results presented here show that loss of progesterone 11 alpha-hydroxylase
      activity in Rhizopus nigricans in aqueous-organic two-liquid phase and cosolvent
      systems correlates well with the concentration of solvent in the cell membranes.
      Rhizopus nigricans is shown to retain full 11 alpha-hydroxylase activity at
      saturating aqueous phase concentrations of hexane and the higher primary
      alcohols. This reflects their inability to attain a critical concentration in the
      cell membranes. The relationship between our own findings and the previously
      described correlation of the logarithm of the partition coefficient with activity
      retention is explained and design parameters are proposed that may be used to
      select solvents for future biocatalytic systems.

PMID- 1366444
TI  - Foam fractionation of proteins and enzymes. II. Performance and modelling.

PMID- 1366445
TI  - Simultaneous determination of glucose, ethanol and lactate in alcoholic beverages
      and serum by amperometric flow injection analysis with immobilized enzyme
      reactors.
AB  - Glucose, ethanol and lactate were determined simultaneously in a flow injection
      system by using a parallel configuration of immobilized enzyme reactors. Hydrogen
      peroxide produced was monitored amperometrically at the potential of +0.65 V vs.
      Ag/AgCl. Linear relations between sensor responses and each species were observed
      in the ranges of 0.02-10 mM (glucose), 5 x 10(-4)-0.1% (v/v) (ethanol) and 0.005
      1 mM (lactate) with correlation coefficients larger than 0.999 for each species.
      The relative standard deviations for 10 successive injections were 1.4, 0.5 and
      1.1% for glucose (1 mM), ethanol (5 x 10(-3)% (v/v] and lactate (0.05 mM),
      respectively. Analysis of serum samples was performed with urate-eliminating
      reactors which were set just before each immobilized enzyme reactor. Interference
      of ascorbate in a serum sample was completely eliminated by using an ascorbate
      eliminating reactor which was set before the sample injection valve. Application
      of the system to alcoholic beverages and control serum was described and the
      results were compared with those of free enzymatic, spectrophotometric analysis
      (F-kit or C-test method).

PMID- 1366446
TI  - A flow injection analysis system involving immobilized NADH oxidase in column
      form for clinical analysis.
AB  - A highly sensitive FIA system for chemiluminometric determination of reduced
      coenzyme, NADH, was developed, using immobilized NADH oxidase from Brevibacterium
      ammoniagenes. The enzyme catalyzed the oxidation of NADH generating hydrogen
      peroxide which emitted chemiluminescence when mixed with luminol and potassium
      ferricyanide. The immobilized enzyme reactor was a mini-column, measuring 1 or 2
      mm in inner diameter and 20 mm in length, and the sample volume was only 1
      microliter per assay, with a feeding speed of one sample per min and a lowest
      detection limit of 10 pmol NADH. A FIA system was also developed for the
      determination of magnesium in human serum, using an enzyme column reactor with
      simultaneously coimmobilized hexokinase, D-glucose-6-phosphate dehydrogenase, and
      NADH oxidase. The performance of the system was as satisfactory as a routine
      colorimetric assay, but with much higher sensitivity.

PMID- 1366447
TI  - Determination of alanine aminotransferase in human serum in an open-closed flow
      injection configuration.
AB  - Open-closed flow injection systems allow the development of methods based on
      multidetection by using conventional detectors. The methods proposed here for the
      determination of alanine aminotransferase (ALT) utilize a photometric detector
      included in the closed circuit, which allows one to perform fixed-time and
      reaction-rate measurements whose sensitivity can be increased by using the sum of
      the analytical signals. The methods, with determination ranges between 1 and 500
      U l-1 of ALT, feature sampling frequencies up to 60 h-1. Their application to
      serum samples provided excellent results, with recoveries between 95 and 106% and
      averaging at 99.9%.

PMID- 1366448
TI  - Fluorometric determination of urea by flow injection analysis.
AB  - Urea was determined using fluorometry with flow injection analysis. O
      phthalaldehyde (OPA) reacts with enzymatically generated ammonia and sulfite in
      alkaline medium to give a highly fluorescent compound that has an excitation
      wavelength of 372 nm and an emission wavelength of about 430 nm. The method is
      more selective to ammonia than the one which uses mercaptoethanol in place of the
      sulfite. Urease was immobilized to a Pall Immunodyne membrane which is
      commercially available. The immobilization occurs through covalent bonding which
      results in a highly stable enzyme preparation. The enzymatic membrane was fitted
      in a 5 cm long, 0.125 inch o.d. Teflon tubing which served as the enzymatic
      reactor. The system is difficult to use for the analysis of urea in serum because
      some compounds normally present in serum fluoresce at the same wavelength. This
      results in higher values for urea. If the reaction system is to be used for the
      evaluation of urea in serum, a blank should be run so that urea concentration can
      be calculated by difference.

PMID- 1366450
TI  - An automated spectrophotometric flow-injection procedure for the determination of
      cellulase activity in bioreactor preparations.
AB  - A spectrophotometric procedure for the determination of cellulase activity in
      precipitated bioreactor preparations and culture filtrates is described. It is
      based on the determination of reducing sugar produced by the action of the enzyme
      on carboxymethylcellulose. The reducing sugar is derivatized with p-aminobenzoyl
      hydrazide and permits a limit of detection of 0.1 U ml-1 cellulase in the
      presence of background sugar, with a sampling rate of 5 h-1. The method can
      readily be applied to the determination of any carbohydrase acting on soluble
      substrates and producing reducing sugars, e.g. amylase, dextranase, xylanase,
      glucanase and polygalacturonase.

PMID- 1366449
TI  - Prerequisites for the on-line control of microbial processes by flow injection
      analysis.
AB  - Problems associated with the use of biosensors in process control, e.g.
      difficulties of sterilization and sensor fouling, are shortly displayed, and
      possibilities to overcome them are outlined. The advantages of flow injection
      analysis (FIA) are demonstrated and examples for efficient sampling systems
      connected with this method are reviewed. Special emphasis is given to problem
      orientated sample pretreatments, preventing fast inactivation of immobilized
      enzymes in the analysis system. Examples of problem-orientated sample
      pretreatment units are given. A proposal for a computer-controlled self
      calibrating FIA system is given.

PMID- 1366451
TI  - Monitoring of enzymes during chromatographic separations.
AB  - An on-line enzyme assay is presented based on flow injection techniques combined
      with fluorimetric detection. It allows to monitor NAD-dependent oxidoreductases
      during the purification of microbial crude extracts or partially purified enzymes
      by fast protein liquid chromatography (FPLC) in a near real-time mode. The
      arrangement is simple and can be easily integrated in the chromatographic system
      avoiding dead volumes. A high measuring frequency (up to 180 samples h-1) and a
      short response time (10-30 s) are achieved. The method has a low limit of
      detection (approximately 0.01 U ml-1), and a good reproducibility (1-4%), the
      injected sample volume is only 2 microliters.

PMID- 1366452
TI  - Urease immobilized on chitosan membrane: preparation and properties.
AB  - Urease was covalently immobilized on glutaraldehyde-pretreated chitosan
      membranes. The optimum immobilization conditions were determined with respect to
      glutaraldehyde pretreatment of membranes and to reaction of glutaraldehyde
      pretreated membranes with urease. The immobilized enzyme retained 94% of its
      original activity. The properties of free and immobilized urease were compared.
      The Michaelis constant was about five times higher for immobilized urease than
      for the free enzyme, while the maximum reaction rate was lower for the
      immobilized enzyme. The stability of urease at low pH values was improved by
      immobilization; temperature stability was also improved. The optimum temperature
      was determined to be 65 degrees C for the free urease and 75 degrees C for the
      immobilized form. The immobilized enzyme had good storage and operational
      stability and good reusability, properties that offer potential for practical
      application.

PMID- 1366453
TI  - Growth and hyoscyamine production of 'hairy root' cultures of Datura stramonium
      in a modified stirred tank reactor.
AB  - The growth and hyoscyamine production of transformed roots of Datura stramonium
      have been examined in a modified 14-1 stirred tank reactor in both batch and
      continuous fermentations on media containing half or full strength Gamborg's B5
      salts and at three different temperatures. Under a range of conditions, roots
      grown on half strength B5 salts with 3% w/v sucrose had a higher dry matter
      content (up to 8.3% w/w) and a higher hyoscyamine content (up to 0.52 mg.g-1 wet
      weight) than roots grown on full strength B5 salts with the same level of sucrose
      (up to 4.6% w/w dry matter and up to 0.33 mg hyoscyamine g-1 wet weight). Growth
      at 30 degrees C was initially faster than at either 25 degrees C or 35 degrees C
      and by day 12, the drained weight of roots in the fermentor at 30 degrees C was
      about fourfold greater than at 25 degrees C and twice that at 35 degrees C. The
      ultimate hyoscyamine levels attained (approximately 0.5 mg.g-1 wet weight) were
      similar at both 25 degrees C and 30 degrees C but some 40% lower at 35 degrees C.
      Final packing densities of 70% w/v were achieved for roots after 37 days growth
      at 25 degrees C and the highest production rate of 8.2 mg hyoscyamine 1(-1) per
      day was obtained for roots grown at 30 degrees C. In continuous fermentation at
      25 degrees C, the release of hyoscyamine into the culture medium was low (less
      than 0.5% w/w of the total) but was up to sevenfold higher in fermentors operated
      at 30 degrees C or 35 degrees C.

PMID- 1366454
TI  - A study of N- and P-dependence of nikkomycin production in continuous culture
      with immobilized cells.
AB  - The influence of nitrogen and phosphate on the biosynthesis of nikkomycin was
      studied in chemically defined medium. Cells of Streptomyces tendae were
      immobilized on porous glass particles in a fluidized-bed reactor for continuous
      production of nikkomycin. Phosphate had no significant influence on the
      biosynthesis of nikkomycin. However, even a very low concentration of phosphate
      in the production medium (0.0125 mmol/l) resulted in microbial growth on the
      particles. The concentration of nitrogen was highly effective in the regulation
      of the biosynthesis of nikkomycin. A high level of antibiotic production (maximum
      3.05 mg/g dry cell weight per hour) was maintained for a period of about 200 h in
      a medium that contained nitrogen at a concentration of 0.2 g NH4NO3/l.

PMID- 1366455
TI  - The use of free and immobilised Arthrobacter simplex in organic solvent/aqueous
      two-liquid-phase reactors.
AB  - The use of free and immobilised Arthrobacter simplex (NCIB 8929) for steroid
      delta 1-dehydrogenation in two-liquid-phase, stirred-tank reactors has been
      compared. Product formation is related to the logarithm of the water-octanol
      partition coefficient (log P) of the organic solvent employed, but the
      relationship is different for the two forms of the biocatalyst. No reaction was
      seen with either biocatalyst in media containing solvents of log P less than or
      equal to 2.5. For free bacteria, product formation rose linearly with log P
      thereafter to a maximum at a value of 9.8. With immobilised bacteria, product
      formation reached a maximum with a solvent of log P = 4.0 and remained constant
      with solvents of higher log P value. Consequently extended reactor operation was
      possible with immobilised bacteria, and the production of high quality (greater
      than 95% purity) steroid product was demonstrated.

PMID- 1366456
TI  - Transformation of microcrystalline hydrocortisone by free and immobilized cells
      of Arthrobacter simplex.
AB  - The transformation of microcrystalline hydrocortisone by free and immobilized
      cells of Arthrobacter simplex resulted in formation of prednisolone. The effect
      of medium composition, non-ionogenic surfactants and exogenous electron acceptors
      on the delta 1-dehydrogenase activity of free and immobilized cells is described.

PMID- 1366457
TI  - Isolation and characterization of a 2-(2,4-dichlorophenoxy) propionic acid
      degrading soil bacterium.
AB  - The 2-(2,4-dichlorphenoxy)propionic acid (2,4-DP)-degrading bacterial strain MH
      was isolated after numerous subcultivations of a mixed culture obtained by soil
      column enrichment and finally identified as Flavobacterium sp. Growth of this
      strain was supported by 2,4-DP (maximum specific growth rate 0.2 h-1) as well as
      by 2,4-dichlorophenoxyacetic acid (2,4-D), 4-(2,4-dichlorophenoxy)butyric acid
      (2,4-DB), and 2-(4-chloro-2-methylphenoxy)propionic acid (MCPP) as sole sources
      of carbon and energy under aerobic conditions. 2,4-DP-Grown cells (10(8] of
      strain MH degraded 2,4-dichlorophenoxyalkanoic acids, 2,4-dichlorophenol (2,4
      DCP), and 4-chlorophenol at rates in the range of 30 nmol/h. Preliminary
      investigations indicate that cleavage of 2,4-DP results in 2,4-DCP, which is
      further mineralized via ortho-hydroxylation and ortho-cleavage of the resulting
      3,5-dichlorocatechol.

PMID- 1366458
TI  - Kinetic studies of acetate fermentation by Methanosarcina sp. MSTA-1.
AB  - The effect of three parameters (initial acetate concentration, temperature and
      pH) on the acetoclastic reaction was studied with the thermophilic methanogenic
      bacterium Methanosarcina sp. MSTA-1. The optimum temperature for growth ranged
      around 55 degrees C, and optimum pH was 6.5-7.5, giving a minimum generation time
      of 12.6-13.9 h (mu max = 0.050-0.055 h-1) and a maximum value of the specific
      acetate consumption rate (qmaxs) of 14-20 mmol/g cells per hour. Contrary to the
      methane yield, the growth yield was found to be dependent on culture conditions,
      especially on incubation temperature. Methanosarcina sp. MSTA-1 showed a low
      affinity for acetate substrate. Growth at 55 degrees C and at constant pH 7
      resulted in a Km value and a threshold acetate concentration of 10.7 mM and 0.7
      mM, respectively.

PMID- 1366459
TI  - Amplifying genes: PCR and its alternatives.

PMID- 1366460
TI  - Affinity partitioning of bioproducts.

PMID- 1366461
TI  - Quantitative flow measurements in bioreactors by nuclear magnetic resonance
      imaging.
AB  - We have developed nuclear magnetic resonance (NMR) flow imaging techniques to
      measure fluid flow in a cell-free hollow fiber bioreactor (HFBR). Using 1H NMR we
      track the motion of protons and obtain velocity distributions as a function of
      position and time. These measurements enable the visualization of flow patterns
      needed for module design and for establishing desired operating conditions.
      Uneven flow in the cell-containing region of an HFBR can result in concentration
      gradients and uneven cell distribution that may lead to reduced cell viability.
      Results from this non-invasive method could be used to design more efficient cell
      bioreactors or membrane separation devices.

PMID- 1366463
TI  - Dating PCR.

PMID- 1366462
TI  - Expression and secretion of a functional scorpion insecticidal toxin in cultured
      mouse cells.
AB  - We have expressed a synthetic gene encoding the insecticidal neurotoxin of
      scorpion Androctonus australis (AaIT) in NIH/3T3 mouse fibroblast cells under the
      transcriptional control of a murine retroviral long terminal repeat. The
      secretion of the toxin into the culture medium was directed by the signal peptide
      of human interleukin-2. The recombinant AaIT produced was selectively toxic to
      yellow-fever mosquito larvae and harmless to mice.

PMID- 1366464
TI  - Kirishi controversy, continued.

PMID- 1366465
TI  - Pushchino: biotechnology capital of the USSR.

PMID- 1366466
TI  - Integrated design for mammalian cell culture.

PMID- 1366467
TI  - Companies targeting drug delivery.

PMID- 1366468
TI  - Market infiltration in filtration.

PMID- 1366469
TI  - A new method for protein crystallization using high pressure.
AB  - Crystallization methods for proteins have been the subject of decades of
      development yet protein crystallization remains the limiting step in structural
      studies. We present here a new method for protein crystallization--based on the
      use of high pressure--that enabled us to accelerate dramatically the growth of
      glucose isomerase crystals. We think this method may have a more general utility.

PMID- 1366470
TI  - Delivering protein drugs orally.

PMID- 1366471
TI  - Prophetic pitfalls.

PMID- 1366472
TI  - Long-term continuous synthesis of aspartame precursor in a column reactor with an
      immobilized thermolysin.
AB  - N-(Benzyloxycarbonyl)-L-asparty-L-phenylalanine methyl ester, the precursor of
      the synthetic sweetener aspartame, was continuously synthesized in an immobilized
      thermolysin plug-flow type reactor at 25 degrees C with the substrates (N
      benzyloxycarbonyl-L-aspartic acid and L-phenylalanine methyl ester) dissolved in
      ethyl acetate. The immobilized enzyme was quite stable in ethyl acetate
      containing 2.5% 0.01 M 2-(N-morpholino)ethanesulphonic acid-NaOH buffer, pH 6.0,
      and 20 mM CaCl2 with or without the substrate at 25 degrees C. By periodically
      washing the column, we could conduct a continuous reaction for over 500 h with an
      average yield of 95% and a space velocity of 1.85 h-1.

PMID- 1366473
TI  - Investigations on cephalosporin C adsorption kinetics and equilibria.
AB  - The kinetics and equilibria of cephalosporin C adsorption on different commercial
      adsorbents were investigated. Adsorption isotherms could be analysed according to
      the Brunauer, Emmett and Teller theory. For the interpretation of adsorption
      kinetics it was necessary to develop a more complex model comprising both a rapid
      and a slower step. An integrated approach combining kinetics and equilibria
      allowed for simulation of the experimental data and can be used as a basis for
      predicting technical approaches such as fluidized-bed technology.

PMID- 1366474
TI  - A technique for rapid protein and peptide analysis.

PMID- 1366475
TI  - The use of powerful software for the quantitation of two-dimensional gel
      electrophoresis data.

PMID- 1366476
TI  - Microscope detection systems for designer biologicals.

PMID- 1366477
TI  - Rapid sequencing of DNA.

PMID- 1366478
TI  - Preparative isoelectric focusing: electric gradients may lead separations in the
      21st century.

PMID- 1366479
TI  - Chromone glycosides from Schumanniophyton magnificum.
AB  - Two new chromone glycosides, schumanniofiosides A and B have been isolated from
      the root bark of Schumanniophyton magnificum and their structures shown to be 2
      methyl-5,7-dihydroxychromone 5-O-beta-D-glucopyranoside and 2-methyl-5,7
      dihydroxychromone 7-O-beta-D-glucopyranosyl-(1----2)-apiofuranoside,
      respectively. The structures were elucidated by a combination of spectral data
      and chemical degradation.

PMID- 1366480
TI  - Biotransformation of digitoxigenin by ginseng hairy root cultures.
AB  - Five new compounds (three esters and two glycosides) and seven previously
      reported compounds were isolated as biotransformation products of digitoxigenin
      by ginseng hairy root cultures. The new esters and glycosides were elucidated as
      digitoxigenin stearate, digitoxigenin palmitate, digitoxigenin myristate, 3
      epidigitoxigenin beta-D-gentiobioside and digitoxigenin beta-D-sophoroside using
      1H and 13CNMR and FAB mass spectral data. Biotransformations involving
      esterification (of stearic acid, palmitic acid, myristic acid and lauric acid)
      and glycosylation (of gentiobiose and sophorose) of digitoxigenin have been
      demonstrated for the first time in the plant cell and tissue cultures. The hairy
      roots showed high glycosylation ability to the digitoxigenin molecule.

PMID- 1366481
TI  - A galactomannan from Crotalaria medicaginea seeds.
AB  - A polysaccharide isolated from the seeds of Crotalaria medicaginea is composed of
      D-galactose and D-mannose in the molar ratio of 10:31. Structural studies were
      performed by methylation analysis, partial acid hydrolysis, chromic oxide
      oxidation, mild hydrolysis with dilute oxalic acid and 13CNMR analysis of the
      polymer.

PMID- 1366482
TI  - Steroidal glycosides from Agave cantala.
AB  - Two new steroidal glycosides, agaveside A and B, isolated from the fruits of
      Agave cantala were characterized as 3 beta-O-[beta-D-xylopyranosyl-(1----2),beta
      D-xylopyranosyl-(1----3), beta-D-glucopyranosyl-(1----3)-[beta-D-xylopyranosyl-(1
      ---3)-beta-D- galactopyranosyl-(1----2)]-beta-D-glucopyranosyl]-(25R)-5 alpha
      spirostane and 3 beta-O-[beta-D-xylopyranosyl-(1----2), beta-D-xylopyranosyl-(1--
      -3)-beta-D-glucopyranosyl-(1----3)- [beta-D-galactopyranosyl-(1----2)]-beta-D
      glucopyranosyl]-(25R)-5 alpha-spirostane. The structures were elucidated by a
      combination of 13CNMR spectroscopy, chemical degradation and fast atom
      bombardment mass spectrometry.

PMID- 1366483
TI  - Conceptual design of a cellular filter to remove trace viral contaminants in
      blood.
AB  - Various process alternatives and designs of using a filter containing cellular
      adsorbents to remove trace viral contaminants from blood and other protein
      solutions have been studied. Sterilization charts have been developed that can be
      used to estimate the filter size required to achieve a desired sterilization
      criterion. A parametric study was carried out to identify various process
      parameters that may affect this physical trace removal process. It has been
      demonstrated that the adsorption rate constant is a critical parameter in the
      design of an efficient cellular filter for viral contaminant removal. This
      constant is characteristic of the virus-cell system under consideration and is
      shown to be particularly sensitive to the cell surface receptor density,
      adsorbent diameter, and fluid flow rate. Higher log titer reduction in virus
      concentrations can be achieved with low flow rates and no recycle. Preliminary
      analyses indicate the feasibility of using a magnetically stabilized fluidized
      filter (MSFF) reactor design for effective virus removal from these complex
      solutions.

PMID- 1366484
TI  - Chemical decomposition of glutamine in cell culture media: effect of media type,
      pH, and serum concentration.
AB  - The chemical decomposition of glutamine to ammonia and pyrrolidonecarboxylic acid
      was studied at 37 degrees C in a pH range of 6.8-7.8 in different media
      preparations containing various amounts of fetal bovine serum. The media type
      influenced the decomposition rate, and the first-order rate constants increased
      with increasing pH values. The serum concentration had little or no effect on the
      decomposition rate. The importance of chemical decomposition of glutamine on the
      analysis of glutamine and ammonia metabolism was illustrated by an example of
      batch cultivation of a hybridoma cell line. The difference between the apparent
      uptake rate of glutamine and the actual uptake rate (which is corrected for the
      chemical decomposition) is shown to be as high as 200%. Similar discrepancy
      between the apparent and actual ammonia production rate is observed. Mathematical
      analysis was carried out to develop the relationship between the apparent and
      actual glutamine uptake and ammonia production rates. The analysis reveals that
      there are three important dimensionless parameter ratios that govern the
      difference between the apparent and actual glutamine uptake and ammonia
      production rates.

PMID- 1366485
TI  - Multimolecular process in a packed-bed immobilized enzyme reactor: numerical
      simulation and back-mixing effects.
AB  - In a previous report, we presented a new analytical model describing the
      performance of a packed-bed catalytic unit, where the reaction between two
      cosubstrates is catalyzed by an enzyme immobilized on a porous carrier. The model
      explicitly takes into account the changes in concentrations of both cosubstrates
      along the reactor, as well as the hydrodynamic regimen (i.e., back-mixing)
      prevailing in the packed bed. In the present report, and on the basis of the
      procedures developed, we present a detailed analysis of the performance of the
      reactor. With numerical simulations, the effects of internal diffusion
      limitations, the depth of the pores, the substrates' concentration in the feed,
      and kinetic parameters are evaluated. Particular attention is also given here to
      the back-mixing effects prevailing in the reactor. An experimental procedure for
      assessing their extent is described.

PMID- 1366486
TI  - Affinity immobilization of a genetically engineered bifunctional hybrid protein.
AB  - Protein A from Staphylococcus aureus (SpA) is a receptor for the Fc domain of
      several classes of antibodies including immunoglobin G (IgG). A hybrid protein
      consisting of protein A and the enzyme beta-lactamase has been constructed using
      recombinant DNA techniques. The functional characteristics of the hybrid protein
      adsorbed on IgG-coated Sepharose matrices were studied in detail and compared to
      those of (i) the hybrid protein in solution and (ii) beta-lactamase covalently
      immobilized on CNBr-activated Sepharose. Protein A--beta-lactamase bound tightly
      and specifically to IgG-Sepharose and could be stored for at least 4 weeks
      without dissociation. The rate of penicillin G hydrolysis by the beta-lactamase
      domain of the immobilized hybrid protein was found to depend on the amount of IgG
      covalently coupled to the support. For all IgG loads, higher specific activities
      and lower Km values relative to covalently immobilized beta-lactamase were
      obtained. Adsorption of the hybrid protein on the support resulted in increased
      stability to thermal deactivation. These results indicate that bifunctional
      hybrid proteins can be useful for the affinity immobilization of enzymes.

PMID- 1366487
TI  - Protein separation using membrane-encapsulated soluble ligand conjugates.
AB  - A new approach for isolating and recovering biological macromolecules using
      membrane-encapsulated soluble ligand conjugates was investigated. Membrane
      encapsulated solid adsorbents have been successfully developed and employed in
      our laboratory to isolate and purify proteins and enzymes directly from culture
      broths. This new concept also makes it possible to use soluble ligand conjugates
      instead of solid adsorbents inside membrane capsules. In this work, model
      membrane-encapsulated soluble and insoluble ligands comprising Blue Dextran and
      Blue Sepharose entrapped within calcium alginate membranes were studied to
      compare adsorption characteristics such as capacities and rates. Experimental
      results suggest that membrane-encapsulated soluble ligands may be expected to
      result in higher overall adsorption capacity compared to membrane-encapsulated
      solid adsorbents with comparable adsorption rates.

PMID- 1366488
TI  - Biotechnology in Japan: Bioreactor system for the chemical industry.

PMID- 1366489
TI  - Yeasts in biodegradation and biodeterioration processes.

PMID- 1366490
TI  - Methods for the genetic engineering of yeasts.

PMID- 1366491
TI  - Yeast as a host for the production of macromolecules of prophylactic or
      therapeutic interest in human health care.

PMID- 1366492
TI  - Piezoelectric crystal biosensors.

PMID- 1366493
TI  - An enhanced-response system for performing chemiluminescent and bioluminescent
      tests.

PMID- 1366494
TI  - Patents and technology transfer.
AB  - Although the discovery and transfer of technology from universities to industry
      has been taking place for many years, the surge of activity in areas related to
      biotechnology, over the past fifteen years, has been remarkable. As the very
      essence of university research requires rapid publication of results, it is
      particularly important that timely patenting activity take place if an orderly
      and profitable transfer of technology is to occur.

PMID- 1366495
TI  - HIV-1 testing: product development strategies.
AB  - Strategies for the development of diagnostic products for acquired immune
      deficiency syndrome (AIDS) are inextricably linked to the status of our knowledge
      of the human immunodeficiency virus (HIV) and the events associated with the
      pathogenesis of AIDS. This review traces product development strategies from 1984
      to the present day. Product development activities in the HIV-1 antibody
      screening test market were a response to the need to remove contaminated units
      from the blood supply. With the successes in screening blood and blood products,
      there has been a shift towards product development for personal health care and
      applicant suitability. Identification of markers for disease progression and the
      need to monitor therapeutic efficacy is now leading to tests for patient disease
      staging, monitoring and prognosis.

PMID- 1366496
TI  - Approaches to HIV vaccine design.
AB  - Contemporary vaccines are relying increasingly on modern biotechnology and a
      vaccine against the AIDS virus is expected to depend even more on new
      technological advances. Four basic areas of vaccine development are discussed in
      this context: (1) selection and preparation of candidate immunogens; (2)
      presentation of immunogens to the immune system; (3) pre-clinical testing of
      vaccine candidates; and (4) monitoring of vaccine clinical trials.

PMID- 1366497
TI  - Bioconversions of aliphatic compounds by Pseudomonas oleovorans in multiphase
      bioreactors: background and economic potential.
AB  - Pseudomonas oleovorans can grow on linear alkanes and alkenes in the hexane to
      dodecane range by virtue of enzymes encoded by the alk genes. By introducing
      selected alk genes into Pseudomonas strains and by supplying alkanes in the
      growth medium as a bulk liquid phase, specific alkane oxidation products can be
      accumulated in the alkane phase. We review the genetics and enzymology of the alk
      system and the potential of bioconversions in two-liquid-phase bioreactors, and
      suggest that such systems might eventually allow the biotechnological production
      of intermediate value compounds.

PMID- 1366498
TI  - Protein-based medical adhesives.
AB  - There are many naturally occurring adhesive proteins which have potential for
      application in medicine and dentistry. Cloning and expression of their genes
      enables the modes of action of these proteins to be better understood and
      increases their availability for practical applications. This article
      concentrates on the adhesive protein from the blue mussel Mytilus edulis but also
      describes medical adhesives based on fibrin isolated from human blood.

PMID- 1366499
TI  - Polypeptide growth factors--a growth area for biotechnology.

PMID- 1366500
TI  - Alginate as immobilization matrix for cells.
AB  - In recent years, entrapment of cells within spheres of Ca2+ alginate has become
      the most widely used technique for immobilizing living cells. This versatile
      method includes applications ranging from immobilization of living or dead cells
      in bioreactors, immobilization of plant protoplasts for micropropagation and
      immobilization of hybridoma cells for production of monoclonal antibodies, to
      entrapment of animal cells for implantation of artificial organs. This review
      evaluates the potential of this method on the basis of the current knowledge of
      structural and functional relationships in alginate gels.

PMID- 1366501
TI  - Supercritical fluid extractions in biotechnology.
AB  - Over the past decade, supercritical fluid (SCF) extraction has been shown to
      deserve consideration as an alternative to liquid-liquid extraction or
      distillation. Most current commercial applications of SCF extraction involve
      biologically produced materials; the technique may be particularly relevant to
      extraction of biological compounds in cases where there is a requirement for low
      temperature processing, high mass-transfer rates and negligible carry over of
      solvent into the final product. New advances, in which extraction is combined
      with reaction or crystallization steps, may further increase the attractiveness
      of SCFs in the bioprocessing industries.

PMID- 1366502
TI  - High efficiency transformation of intact yeast cells by electric field pulses.
AB  - We have developed an efficient method that electrically introduces DNA into
      intact yeast cells. Saccharomyces cerevisiae was used as a model in order to
      optimize the transformation protocol. Transformation efficiencies of 10(7)
      transformants/micrograms of plasmid DNA were obtained with a square wave electric
      pulse of 2.7 kV/cm during 15 milliseconds. The technique is simple and rapid.
      Even small quantities of DNA (100 pg) can be used to transform 10(8) cells.
      Important parameters are the pulse field strength and duration. Pretreatment of
      the yeast cells in the early phase of exponential growth with dithiothreitol
      increases transformation efficiency. The method has been successfully applied to
      various strains of S. cerevisiae as well as to other types of yeast.

PMID- 1366503
TI  - Pulsed-field separations: continued evolution.

PMID- 1366504
TI  - Immunoaffinity adsorption: process-scale isolation of therapeutic-grade
      biochemicals.
AB  - This review describes immunoaffinity purification as a tool for the process-scale
      isolation of high-value, therapeutic-grade biochemicals from complex media. To
      this end, practicalities of activation, antigen coupling and operation in anti
      human IgG monoclonal antibody recovery have been studied using cyanogen-bromide
      activated Sepharose CL-4B and composite Macrosorb K4AX immobilised with
      polyclonal human IgG as a model for general immunoaffinity systems. The
      characteristics required of solid phases are discussed in the context of the
      efficient application of bioselective processes early in the purification
      sequences. The importance of the technique for isolating biologically active
      biomolecules for in-vivo administration has been discussed in the light of
      current, stringent regulatory requirements. Finally, the prospect of scale-up and
      automation of the technique has been evaluated.

PMID- 1366505
TI  - Cooperative interactions in transcriptional regulation.
AB  - Cooperative interactions between regulatory proteins and RNA polymerase are a
      common feature of transcriptional systems. We have developed a method, based on
      the electrophoresis mobility shift assay, for the measurement of cooperative
      effects in the binding of proteins to DNA restriction fragments. Using this
      approach we have identified a hitherto unknown interaction between the E. coli
      lactose repressor and CAP proteins. We suggest that this interaction plays a role
      in the control of the lactose operon that is not predicted by current regulatory
      models.

PMID- 1366506
TI  - Gene construction and mutagenesis for site specific modification of protein with
      carbohydrate.
AB  - We reported the construction of the structural gene for trans-activator (Tat)
      protein of human immunodeficiency virus. While maintaining the same amino acid
      sequence as the viral protein, the corresponding nucleotide sequence was modified
      to create additional recognition sites for restriction endonucleases and to
      prevent basepair mismatch during gene assembly. The oligonucleotides were
      synthesized chemically, purified and assembled into five gene blocks. The gene
      blocks were cloned into plasmid vectors and later reassembled into a complete
      gene. The use of gene blocks facilitated in vitro mutagenesis by the cassette
      mutagenesis method.

PMID- 1366507
TI  - Molecular cloning of the xylL-xylE region from the P. putida TOL plasmid, pDK1.
AB  - A 5.2 kilobase EcoRI restriction fragment from the Pseudomonas putida HS1 TOL
      plasmid pDK1, encoding a portion of the lower toluene degradation pathway, was
      cloned into the E. coli plasmid pBR325. A detailed map of the restriction
      endonuclease sites was constructed and the nucleotide sequence of three
      contiguous XhoI fragments, with a combined total length of approximately 3.9
      kilobases, has been investigated. This region was determined to contain a total
      of four separate open reading frames, each preceded by an identical putative
      ribosome-binding site (nucleotide sequence of 5'-GAGGTG-3'). These open reading
      frames have been tentatively identified as encoding the lower pathway enzymes
      catechol 2,3-dioxygenase (C23O) and 1,2-dihydroxycyclohexa-3,5-diene carboxylate
      dehydrogenase (DHCDH) and a subunit of the toluate 1,2-dioxygenase complex (TO).

PMID- 1366508
TI  - Tumor cell drug resistance and its reversal.
AB  - Tumors that formerly were uniformly fatal can now be cured by cancer
      chemotherapy. However, successful anticancer therapy is faced by many obstacles,
      such as excessive normal tissue toxicity and drug resistance. Tumor drug
      resistance may be either intrinsic or acquired. The multidrug resistance (MDR) is
      a unique phenomenon and is characterized by tumor resistance to various
      structurally unrelated drugs. Known mechanisms for MDR include overexpression of
      a membrane P-glycoprotein 170 and elevated cellular levels of reducing agents,
      such as glutathione (GSH). Currently available strategies for overcoming drug
      resistance include competitive inhibitors of the P-glycoprotein 170, inhibitors
      of GSH synthesis, and adjuvant therapy with hyperthermia. Development of drug
      resistance is analogous to a physiological detoxification mechanism and may
      continue to limit the effectiveness of cancer chemotherapy in the near future.

PMID- 1366509
TI  - Prophetic patents in biotechnology.

PMID- 1366510
TI  - The tryptophan synthase multienzyme complex: exploring structure-function
      relationships with X-ray crystallography and mutagenesis.
AB  - The bifunctional tryptophan synthase alpha 2 beta 2 complex that catalyzes the
      final two reactions in tryptophan biosynthesis is a classic example of a
      multienzyme complex that "channels" a metabolic intermediate (indole) between two
      active sites. The three-dimensional structure of the alpha 2 beta 2 complex from
      Salmonella typhimurium reveals that the four polypeptide subunits are arranged in
      an extended alpha beta beta alpha order forming a complex 150 A long. The active
      sites of the neighboring alpha and beta subunits are separated by about 30 A and
      appear to be connected by a tunnel, which may facilitate the intramolecular
      transfer of indole. The active site of the alpha subunit, which is centrally
      located near one end of an eight-fold alpha/beta barrel structure, contains the
      sites of most of the missense mutations which were identified as key residues by
      Yanofsky and colleagues in early genetic studies. Site-directed mutagenesis is
      being used to replace residues found in the active sites of the alpha and beta
      subunits in order to probe the mechanism of catalysis. Recombinant DNA technology
      should also be useful in analyzing protein-protein interaction, protein folding
      and the channeling phenomenon.

PMID- 1366511
TI  - The secretion of human serum albumin from the yeast Saccharomyces cerevisiae
      using five different leader sequences.
AB  - We demonstrate the secretion of human serum albumin into the culture supernatant
      from the yeast Saccharomyces cerevisiae. Studies with five KEX2 processed leader
      sequences, namely the S. cerevisiae alpha factor, the natural human serum
      albumin, the Kluyveromyces lactis killer, a natural human serum albumin/alpha
      factor fusion, and a Kluyveromyces lactis killer/alpha factor fusion leader, are
      described. We show that the leader sequence used to direct secretion influences
      the quantity and quality of the secreted product. In designing secretion systems
      for heterologous proteins, one aims to maximise both the yield and fidelity of
      the product. Our results indicate that the choice of leader sequence and its
      relationship to the structural protein under study are crucial to the success of
      this process.

PMID- 1366512
TI  - Use of the Escherichia coli SSB gene to prevent bioreactor takeover by
      plasmidless cells.
AB  - Reactor takeover by plasmidless cells is a major problem encountered when
      producing proteins from plasmid-borne genes in genetically engineered bacteria.
      We have approached this problem by deleting the essential ssb gene from the
      Escherichia coli chromosome and placing it on a plasmid. Plasmidless cells do not
      accumulate even after growing such strains under non-selective continuous culture
      conditions for extended periods of time. Other ssb-containing plasmids can be
      readily introduced into this E. coli strain by a plasmid-displacement technique.
      Using this system, we have achieved very high levels of beta-lactamase production
      in continuous culture without selective pressure.

PMID- 1366513
TI  - Monoclonal antibodies as reagents.

PMID- 1366514
TI  - Development of a piezoelectric immunosensor for the detection of Salmonella
      typhimurium.
AB  - A piezoelectric biosensor has been developed for the detection of Salmonella
      typhimurium. The antibody to Salmonella was immobilized on the crystal by various
      immobilization procedures. The best result was obtained when antibody was
      immobilized on the crystal precoated with a thin layer of polyethyleneimine. The
      response of the coated crystal for S. typhimurium in a microbial suspension was
      in the range of 10(5) to 10(9) cells ml-1. The time required for a complete
      interaction between the crystal and the cells appeared to depend upon the cell
      concentration of the analyzed sample. The antibody-bound crystal lost no activity
      over 4 days at 4 degrees C and it could be reused for 6-8 consecutive assays.

PMID- 1366515
TI  - Hydrolysis of concentrated sucrose syrups by invertase immobilized on anion
      exchanger waste cotton thread.
AB  - Yeast invertase was immobilized on polyethyleneimine-coated cotton thread by
      adsorption followed by crosslinking with glutaraldehyde. The thread-bound
      invertase was used as an easily retrievable system for the hydrolysis of 80% w/v
      commercial sucrose syrups. The immobilized enzyme was stable for over 90 days to
      a temperature of 50 degrees C, only when stored in 80% sucrose solution. Above
      this temperature, inactivation of enzyme was observed. The cotton threads were
      used in a batch reactor for hydrolysis of sucrose in about 30 batches carried out
      over a period of 50 days without loss in activity. The threads could also be used
      in a packed bed reactor (1.51) for 97% hydrolysis of 80% sucrose syrups at 50
      degrees C at a rate of about 360 kg per month for a period of 3 months.

PMID- 1366517
TI  - Patent reports.

PMID- 1366516
TI  - Foam fractionation of proteins and enzymes: I. Applications.

PMID- 1366518
TI  - Continuous recombinant bacterial fermentations utilizing selective flocculation
      and recycle.
AB  - Selective recycle has successfully been used to maintain an unstable plasmid
      bearing bacterial strain as dominant in a continuous reactor, whereas the culture
      reverts to 100% segregant cells when selective recycle is not used. The plasmid
      bearing strain is slower growing and flocculent; however, when the cells lose
      their plasmid, the resulting segregant cells are nonflocculent and grow at a
      faster rate due to their decreased metabolic burden. Both types of cells exit a
      chemostat and enter an inclined settler where the flocculent plasmid-bearing
      cells are separated from the nonflocculent segregant cells by differential
      sedimentation. The underflow from the cell separator, which is enriched with
      plasmid-bearing cells, is recycled back to the chemostat, while the segregant
      cells are withdrawn off the top of the settler and discarded. The experimental
      results agree well with selective recycle reactor theory. On the basis of the
      theory, a criterion is presented that has been shown to successfully predict
      whether or not a selective recycle reactor can maintain a plasmid-bearing strain.

PMID- 1366519
TI  - Gene expression and the development of live enteric vaccines.
AB  - Rationally attenuated live Salmonella vaccines provide good protection against
      homologous challenge and can act as carriers of heterologous antigens. However,
      the optimum expression system for each heterologous antigen will need to be
      established individually. This will ensure that the antigen in question is
      produced at appropriate levels, in the correctly folded conformation, within or
      at the surface of the carrier cell, and can therefore elicit the optimal immune
      response.

PMID- 1366520
TI  - Biomaterials aspects of porous microcarriers for animal cell culture.
AB  - Porous microcarriers are new support materials with important advantages in both
      industrial cell-culture processes and the culture of cells of medical importance.
      Porous microcarriers are now commercially available with internal architecture
      and surface chemistry suitable for culture of both anchorage-dependent and
      anchorage-independent animal cells.

PMID- 1366522
TI  - Bioconversions in aqueous two-phase systems.
AB  - Bioconversions involving enzymes and/or microbial cells in aqueous two-phase
      systems are reviewed. The partitioning of biocatalysts, substrates, and products
      is discussed in relation to their size. The efficiency of retaining biocatalysts
      in aqueous two-phase systems is summarized in relation to other methods of
      recirculating. The influence of phase components on the activity and the
      stability of enzymatic biocatalysts is exemplified with penicillin acylase and
      the cellulolytic enzyme system, and the effect of phase components on
      biocatalytic living cells is exemplified with the production of alpha-amylase
      with Bacillus sp. Process design costs in bioconversions in aqueous two-phase
      systems are briefly summarized.

PMID- 1366521
TI  - Oriented immobilization of bacterial photosynthetic membrane.
AB  - We have examined a method for oriented immobilization of photosynthetic membrane
      fragments on a solid surface by specific avidin-biotin interaction.
      Photosynthetic membrane fragments from the purple non-sulphur photosynthetic
      bacterium Rhodopseudomonas viridis, of which the H-subunit of the photosynthetic
      reaction centre was biotinylated, was immobilized on an avidin-adsorbed plate.
      Orientation of the immobilized membrane on the plastic plate was checked by an
      antisera binding assay that could react to the respective sides of the membrane:
      the H-subunit side was selectively adsorbed on the plate. Light-induced potential
      and current responses could be measured when the membrane immobilized on the SnO2
      coated glass plate was dried and sandwiched with a counter electrode of Hg. The
      electrical response in the immobilized membrane was much improved in comparison
      with the control (membranes were simply adsorbed on the plate), supporting the
      idea that the membranes have an orientation on solid surfaces.

PMID- 1366523
TI  - Enzymatic synthesis of the precursor of Leu-enkephalin in water-immiscible
      organic solvent systems.
AB  - The precursor of Leu-enkephalin, Z-L-TyrGlyGly-L-Phe-L-LeuOEt, was synthesized
      from amino acid derivatives with three proteinases without the protection of the
      side chain of L-Tyr. First, Z-GlyGlyOBut and Z-L-TyrGlyGlyOBut were synthesized
      in quite a high yield, 83% and 99%, in an aqueous/organic biphasic system by
      papain and alpha-chymotrypsin, respectively. Then, Z-L-Phe-L-LeuOEt was
      synthesized by thermolysin from Z-L-Phe and L-LeuOEt either in buffer or in a
      biphasic system; the yields were 95% and 100%, respectively. The synthesis of Z-L
      TyrGlyGly-L-Phe-L-LeuOEt from Z-L-TyrGlyGly and L-Phe-L-LeuOEt was performed
      effectively by thermolysin immobilized on Amberlite XAD-7 in a buffer and in an
      aqueous/organic biphasic system, as well as in saturated ethyl acetate, while the
      yield was low in reactions by free thermolysin. In the reaction with the
      immobilized enzyme (IME) in saturated ethyl acetate, the maximum yield of the
      precursor of Leu-enkephalin was 68%. The reasons for effective synthesis with IME
      are: (1) higher concentration of L-Phe-L-LeuOEt inside support, which resulted in
      rising the rate of the synthesis reaction and protecting the competitive
      hydrolysis of Z-L-TyrGlyGly by thermolysin, (2) entrapment of the product inside
      the support where thermolysin could not act in the case of reaction in buffer,
      and (3) extraction of the product with the organic solvent in the case of
      reaction in a biphasic system or in saturated organic solvent.

PMID- 1366524
TI  - Development of a gas diffusion FIA system for on-line monitoring of ethanol.
AB  - A flow injection analysis (FIA) system for on-line monitoring of ethanol in
      cultivation media was developed, which combines the selectivity of a gas
      diffusion membrane with the substrate specificity of immobilized alcohol oxidase
      (AOD). The optimization of membrane material and immobilized enzyme was performed
      using different FIA modes such as dual detection and dual injection. A simple
      modification of a polypropylene membrane with silicone enabled a very flexible
      adjustment of the linear range for alcohol detection between 0.0006 and 60% (v v
      1). The ethanol content of cultivation media could be determined continuously
      with a frequency of 120-180 samples per hour with an excellent correlation to gas
      chromatographic analysis (r = 0.9996). The relative standard deviation for 10
      successive injections was lower than 0.5%.

PMID- 1366525
TI  - Flow injection analysis (FIA) based on enzymes or antibodies--applications in the
      life sciences.

PMID- 1366526
TI  - Flow injection analysis and biosensors: applications for biotechnology and
      environmental control.
AB  - Our experience in industrial bioprocess monitoring and environmental control let
      us develop a concept for biosensor research which distinguishes itself from
      other, more popular, approaches. Biosensors must improve and/or simplify existing
      state-of-the-art analysis systems. Only the parallel development of biosensors
      and their complementary metrology leads to industrially sound solutions. The
      combination of flow injection analysis with immobilized enzymes in the form of
      enzyme columns is already used today for the solution of on-line analytical
      problems in bioprocesses and environmental control.

PMID- 1366527
TI  - Microbial isopenicillin N synthase genes: structure, function, diversity and
      evolution.
AB  - Clinically and economically, penicillins and cephalosporins are the most
      important class of the beta-lactam antibiotics. They are produced by a wide
      variety of microorganisms including numerous species of Streptomyces, some
      unicellular bacteria and several filamentous fungi. A key step common to their
      biosynthetic pathways is the conversion of a linear, cysteine-containing
      tripeptide to a bicyclic beta-lactam antibiotic by isopenicillin N synthase.
      Recent successes in the cloning and expression of isopenicillin N synthase genes
      now permit production of a plentiful supply of this enzyme, which may be used for
      structural and mechanistic studies, or for biotechnological applications in the
      creation of novel beta-lactam compounds from peptide analogues. New ideas
      concerning the evolution and prevalence of the penicillin and cephalosporin
      biosynthetic genes have emerged from studies of isopenicillin N synthase genes.

PMID- 1366528
TI  - Adenoviruses as expression vectors and recombinant vaccines.

PMID- 1366530
TI  - Prospects for genetic diagnosis of inherited predisposition to cancer.
AB  - The best long-term prospects for the reduction in the number of deaths due to
      cancer lie with screening and prevention rather than with therapy of the advanced
      disease. Screening efficiency will be improved by the identification of
      individuals at inherited high risk of cancer. Understanding the mechanism of
      predisposition may provide the basis for rational attempts at prevention, as well
      as for new approaches to therapy.

PMID- 1366529
TI  - Engineering proteins for purification.
AB  - Over the past decade, a new protein purification technique has emerged as a
      result of recombinant DNA technology. DNA, encoding additional polypeptide or
      protein tags, is fused to the gene of interest. Expression of these gene fusions
      results in protein fusions which may be purified by techniques using the
      properties of the additional polypeptide tag. This has eliminated the need for
      extensive screening and optimization procedures previously required for
      purification.

PMID- 1366531
TI  - Diffusion in immobilized-cell agar layers: influence of bacterial growth on the
      diffusivity of potassium chloride.
AB  - The diffusivity of potassium chloride in composite agar slab/microporous membrane
      structures loaded with various amounts of Escherichia coli whole cells was
      determined using both time-lag and steady-state methods. The diffusion
      coefficient of KCl decreased linearly with the logarithm of the immobilized-cell
      content. The effect exerted by bacterial growth inside the immobilization
      matrices on KCl diffusivity was then investigated. The diffusion coefficient of
      KCl obtained by time-lag analysis decreased during incubation of the immobilized
      cell structures, whereas less consistent results arose from the steady-state
      method. An apparent doubling time for immobilized E. coli, increasing with the
      initial cell content of the gel, was obtained from the calibration relationship
      between KCl diffusivity and the number of organisms in agar.

PMID- 1366532
TI  - Mechanism of formaldehyde biodegradation by Pseudomonas putida.
AB  - Formaldehyde biodegradation by a strain of Pseudomonas putida has been studied.
      The results indicate that this biodegradation is initiated by a dismutation
      reaction, yielding as products formic acid and methanol. The degradation of
      methanol and formic acid begins after exhaustion of formaldehyde in the medium,
      and presents a diauxic pattern: first formic acid is consumed followed by
      methanol. Moreover, cell viability, which is affected by the amount of added
      formaldehyde, has been determined.

PMID- 1366533
TI  - Sites of cadmium uptake in bacteria used for biosorption.
AB  - Electron microscopy and x-ray spectroscopy were used to determine location and
      type of cadmium biosorption on and in bacteria, some of which produced
      extracellular polymers. Examined Arthrobacter and Pseudomonas species appear to
      have detoxification systems that precipitate cadmium internally irrespective of
      whether or not they excrete polymers. Capsular Klebsiella aerogenes strains
      showed minimal intracellular uptake but over a 5-100 mg dm-3 Cd range produced
      the highest net metal removal levels due to significant extracellular adsorption.

PMID- 1366534
TI  - Gel microdroplets and flow cytometry: rapid determination of antibody secretion
      by individual cells within a cell population.
AB  - We report a new method capable of rapidly determining the secretion of
      biologically important macromolecules from each of many individual cells within a
      large population. This method combines flow cytometry with gel microdroplets
      (GMDs), which in this study were agarose particles ranging from about 53 to 88 mu
      in diameter. The GMDs were formed from a liquid 2.5% agarose suspension with
      cells at a concentration which yielded mostly zero or one cell per GMD. A large
      number of extracellular binding sites were also provided within each GMD,
      allowing the capture of secreted molecules, and their subsequent measurement by
      solid phase, fluorescence immunoassay. The method was explored using a model
      system of mouse hybridoma (secreting) and mouse masticytoma (non-secreting)
      cells. The method was able to determine subpopulations of individual cells that
      secreted antibody in less than fifteen hours after receipt of a conventional cell
      suspension.

PMID- 1366535
TI  - Site-directed pegylation of recombinant interleukin-2 at its glycosylation site.
AB  - We have modified recombinant interleukin-2 (rIL-2) to facilitate site-directed
      covalent attachment of monomethoxy polyethylene glycol (PEG). The site chosen for
      modification and subsequent covalent attachment with PEG (PEGylation) was the
      single glycosylation position found in the native interleukin-2 (IL-2). The
      mutant protein was expressed in E. coli, purified, and PEGylated with a PEG
      maleimide reagent to obtain PEG-cys3-rIL-2. The PEG-cys3-rIL-2 had full
      bioactivity relative to the unmodified molecule and had an increase in
      hydrodynamic size sufficient to increase its systemic exposure by approximately 4
      fold. This method has general applicability for modifying any therapeutic protein
      at a specific site and thereby alter its potency. In particular, it can be used
      to attach PEG to prokaryotically expressed recombinant proteins at their
      glycosylation sites.

PMID- 1366536
TI  - Environmental effects on protein glycosylation.
AB  - Cultured mammalian cells are being used to produce proteins for therapeutic and
      diagnostic use because of their ability to perform complex post-translational
      modifications, including glycosylation. The oligosaccharide moieties can play an
      important role in defining several biological properties of glycoproteins,
      including clearance rate, immunogenicity, and biological specific activity. There
      is a growing interest in defining the factors that influence glycosylation,
      including the cell culture environment. In this review we organize the published
      data from in vitro cell culture and tissue culture studies that demonstrate
      direct effects of the culture environment on N-linked glycosylation.

PMID- 1366538
TI  - Alteration of the specificity of the Streptomyces subtilisin inhibitor by gene
      engineering.
AB  - We have altered the amino acid at the center of the reactive site (methionine 73)
      of Streptomyces subtilisin inhibitor (SSI) by site-directed and cassette
      mutagenesis. Replacement by lysine or arginine resulted in trypsin inhibitory
      activity, replacement only by lysine gave inhibition of lysyl endopeptidase, and
      replacement by tyrosine or tryptophan resulted in inhibition of alpha
      chymotrypsin. The four mutant SSIs retained their native activity against
      subtilisin BPN'. Thus by altering only one amino acid residue at the reactive
      site of SSI to the substrate specificity of the respective protease we could
      successfully change its inhibitory profile.

PMID- 1366537
TI  - Improved production of chymosin in Aspergillus by expression as a glucoamylase
      chymosin fusion.
AB  - We have extended the work on chymosin production in Aspergillus by constructing
      an expression vector in which the cDNA encoding bovine prochymosin B was fused in
      frame immediately following the codon for the last amino acid of the A. awamori
      glucoamylase (glaA) gene. Transformation of A. awamori with this plasmid led to
      the secretion of considerably higher amounts of chymosin than obtained with
      previous chymosin expression vectors. We present evidence that mature chymosin is
      autocatalytically released from the glucoamylase-chymosin fusion protein after
      secretion.

PMID- 1366539
TI  - Amplification and high-level expression of a cDNA for human granulocyte
      macrophage colony-stimulating factor in human lymphoblastoid Namalwa cells.
AB  - We have achieved high-level expression of human granulocyte-macrophage colony
      stimulating factor (GM-CSF) in human lymphoblastoid Namalwa cells by introducing
      and subsequently amplifying an expression vector encoding human GM-CSF and mouse
      dihydrofolate reductase (DHFR). Transformants expressing elevated levels of both
      GM-CSF and DHFR were selected by a step-wise increase in the concentration of
      methotrexate (MTX). Several cell lines resistant in 800 nM MTX have been
      established that express GM-CSF at a rate of 10-20 micrograms/10(6) cells/day.
      The amplified genes are integrated and stably maintained in the chromosomes of
      these cell lines. Analysis of the GM-CSF produced in the amplified Namalwa cells
      revealed that the molecular-size distribution due to varied degrees of
      glycosylation was similar to that observed in the naturally-occurring molecules.

PMID- 1366540
TI  - Growth and product formation of actinomycetes cultivated at increased total
      pressure and oxygen partial pressure.
AB  - Influence of pressure (P) and oxygen partial pressure (PO2) on cultivation of
      various Streptomyces spp. and Micromonospora purpurea was examined in pressurized
      air-lift and stirred tank fermenters. The maximum PO2 was 2100 mbar. Growth and
      product formation of all cultures tested were markedly influenced by PO2 higher
      than 1000 mbar. There is evidence that wild strains are more oxygen tolerant than
      production strains. At a certain PO2 the metabolic activities of all cultures
      were inhibited. However, results obtained with S. aureofaciens and S. rimosus
      indicated an increase in specific product formation rate at elevated pressure.
      With increase in oxygen tension incorporation of oxygen into tetracycline
      molecules was enhanced. Since elevated oxygen tension can either show inhibiting
      effects or may be used for regulation of product formation and selectivity, the
      influence of PO2 should be determined in an appropriate experimental set-up for
      each process.

PMID- 1366541
TI  - Expression of an Erwinia sp. gene encoding diphenyl ether cleavage in Escherichia
      coli and an isolated Acinetobacter strain PE7.
AB  - An Acinetobacter strain PE7 with the ability to grow on salicyclic acid and to
      degrade diphenyl ethers was isolated from a petroleum waste pit in Louisiana. A
      cloned Erwinia sp. dpe gene encoding diphenyl ether cleavage was introduced into
      PE7 in order to enhance its degradative ability. A broad-host-range expression
      plasmid, pDPE2388, was constructed by inserting an SspI-HpaI fragment from a dpe
      gene-containing plasmid, pDPE7321, into the kanamycin resistance gene of plasmid
      pKT230. The DNA fragment contained the dpe gene flanked between sp6 and T7
      promoters. Transconjugants of pDPE2388 plasmid into PE7 were isolated. Expression
      of the dpe gene in Escherichia coli or PE7 displayed a degradative ability to
      cleave the following diphenyl ethers: 4-chlorodiphenyl ether, 4-nitrodiphenyl
      ether, and 4-hydroxydiphenyl ether.

PMID- 1366542
TI  - Degradation of thiophene-2-carboxylate, furan-2-carboxylate, pyrrole-2
      carboxylate and other thiophene derivatives by the bacterium Vibrio YC1.
AB  - A bacterium of the genus Vibrio, capable of degrading thiophene derivatives, was
      isolated from enrichment cultures inoculated with oil-contaminated estuarine mud.
      Of the thiophene derivatives tested, only thiophene-2-carboxylate (T2C),
      thiophene-2-acetate and thiophene-2-carbonyl chloride supported growth, but a
      total of seven were significantly oxidised by resting cells. Furan-2-carboxylate
      (F2C) and pyrrole-2-carboxylate (P2C) also supported growth and were oxidised.
      The heteroatoms of T2C and P2C were released into the media as sulphate and
      ammonia and served as sole sources of sulphur and nitrogen for growth. Mutants
      defective in T2C utilisation (Thc-) were isolated, many being also defective in
      F2C and P2C utilisation.

PMID- 1366543
TI  - Culturing cells in a mechanically active environment.

PMID- 1366544
TI  - Applications of scanning tunneling microscopy to biological materials.

PMID- 1366545
TI  - Shear sensitivity of hybridoma cells in batch, fed-batch, and continuous
      cultures.
AB  - Previously, we observed that CRL-8018 hybridoma cells were more sensitive to well
      defined viscometric shear during the lag and stationary phases than during the
      exponential phase of batch cultures. Some potential hypotheses for explaining the
      increase in shear sensitivity are (1) nutrient limitations that result in a
      decrease in production of specific cellular components responsible for the
      mechanical strength of the cell, (2) nutrient limitations that lead to
      synchronization of the culture in a cell cycle phase that is more sensitive to
      shear, or (3) a link between cell growth and shear sensitivity, such that slowly
      growing cells are more sensitive to shear. Here, the duration of the exponential
      phase was increased with use of fed-batch, and the effect on shear sensitivity of
      the cultures was measured with a viscometric technique. Extension of exponential
      growth resulted in an increased period during which the cells were insensitive to
      shear. Additionally, the shear sensitivity of the cells was constant over a wide
      range of growth rates and metabolic yields in chemostat cultures. These
      observations suggest that as long as the cells are actively (exponentially)
      growing, their shear sensitivity does not depend on the growth rate or metabolic
      state of the cell as expressed by metabolic yields. Thus, hypothesis 3 above can
      be dismissed.

PMID- 1366546
TI  - Structural features of nonionic polyglycol polymer molecules responsible for the
      protective effect in sparged animal cell bioreactors.
AB  - The nonionic surfactant Pluronic F-68 polyol is commonly used to protect cultured
      animal cells from the detrimental effects of sparging. In this study we
      investigated the structural features of the Pluronic F-68 molecule responsible
      for this protective behavior. Poly(oxyethylene)-poly(oxypropylene) block
      copolymer polyols of various molecular weights and percentages of hydrophobe
      (poly(oxypropylene], including both Pluronic and reverse Pluronic polyols, were
      considered. The potential toxicity of these agents was examined in the absence of
      sparging (i.e., in spinner flasks) by using the attachment-independent Sf9 insect
      cell line as a model system. Each polyol resulted in one of three distinct types
      of behavior in these spinner flask experiments: (1) cells lysed at an exponential
      rate, (2) inhibition of cell growth (i.e., no net cell growth), or (3)
      uninhibited cell growth. It was then shown that all of the Pluronic and reverse
      Pluronic polyols that did not inhibit cell growth provided protection from
      sparging in the bioreactors used in this study; thus, finding a polyol that
      protected cells was synonymous with finding one that did not inhibit cell growth.
      The ability of these polyols to protect animal cells in sparged bioreactors was
      found to correlate well with the hydrophilic-lipophilic balance (HLB). Those
      polyols with the largest HLB values were found to be protective agents. These
      poly(oxyethylene)-poly(oxypropylene) polyols were also shown to be more effective
      protective agents than pure poly(oxyethylene); thus, the presence of the
      hydrophobe (poly(oxypropylene] is important in their ability to serve as
      protective agents.

PMID- 1366547
TI  - Effect of preinduction specific growth rate on recombinant alpha consensus
      interferon synthesis in Escherichia coli.
AB  - The effect of preinduction specific growth rate on the yield of recombinant alpha
      consensus interferon in Escherichia coli K-12 was investigated. The cells used in
      the investigation contain a temperature-sensitive, walkaway plasmid bearing an
      insert that codes for alpha consensus interferon. Transcription of the
      recombinant gene is controlled by a lambda repressor/pL promoter system. The
      lambda promoter is regulated by the temperature-sensitive gene cI857 at 30
      degrees C, but at 42 degrees C the promoter is derepressed. The cells were grown
      under glucose-limited conditions in a chemostat at pH 7 and 30 degrees C. Once
      steady state was achieved, the vessel temperature was raised to 42 degrees C and
      a fed-batch mode was initiated. Six dilution rates ranging from 0.025/h to 0.2/h
      were investigated. Cell dry weight, alpha consensus interferon content, glucose
      concentration, acetate concentration, and plasmid stability were measured. At
      each dilution rate, the expression level of alpha consensus interferon (g/g of
      cell dry wt) reached its maximum value approximately 3 h after induction. In
      addition, the expression level of alpha consensus interferon increases 4-fold as
      the dilution rate prior to induction is increased from 0.025/h to 0.2/h.
      Consequently, the expression of recombinant protein produced by E. coli is
      dependent on the preinduction specific growth rate.

PMID- 1366548
TI  - Microbial processes for ascorbic acid biosynthesis: a review.
AB  - L-Ascorbic acid is an important product currently made using the Reichstein
      process, which is mainly chemical. Recently, bacteria have been identified that
      are able to transform in a very efficient way glucose to 2,5-keto-D-gluconic acid
      and this product to 2-keto-L-idonic acid, precursor of L-ascorbic acid. When the
      corresponding strains are used together, it is possible to get 2-keto-L-idonic
      acid directly from glucose. Moreover, new strains have been constructed by
      introducing a gene from a strain responsible for the second step into a strain
      responsible for the first step. By using one of the new strains, the
      transformation can be performed in a single step with only one strain. However,
      the classical process still remains the most competitive.

PMID- 1366549
TI  - Immobilization of biocatalysts with poly(vinyl alcohol) supports.
AB  - Two polymer materials, poly(vinyl alcohol) (PVA) superfine fibers and
      photocrosslinkable PVA bearing styrylpyridinium groups, have been developed to
      immobilize biocatalysts. The former has a large surface consisting of relatively
      large-size pores and the fibers can immobilize a large amount of biocatalyst on
      their surface by ionic interaction. The latter entraps many kinds of biocatalysts
      by cyclodimerization caused by visible light irradiation. The biocatalysts on/in
      these supports maintain high activity and thermal stability. These materials can
      easily be formed into various shapes suitable for various applications. A new
      bioreactor system was constructed for evaluating a variety of biocatalysts and
      supports.

PMID- 1366550
TI  - The membrane bioreactor with coenzyme recycling system.
AB  - Much attention has been paid to membrane bioreactors, especially to the newly
      developed charged membrane bioreactor (CMBR) for recycling the native form of the
      coenzyme NAD(P)H. Charged membranes with anionic groups effectively retained the
      free nicotinamide coenzyme due to the electrostatic repulsion between membrane
      and coenzyme. The capability of the CMBR was demonstrated by the continuous
      production of sorbitol using a multi-enzyme system of NADPH-dependent aldose
      reductase and glucose dehydrogenase. Several important features of the CMBR were
      elucidated by a theoretical model of coenzyme turnover.

PMID- 1366551
TI  - Two-phase system membrane reactor with cofactor recycling.
AB  - For the purpose of constructing a two-phase system reactor the enzymatic process
      of l-menthol production with cofactor recycling was studied as a model. The half
      life of the menthone reductase immobilized onto activated carbon was 4 times as
      high as that of the free enzyme. The enzyme was capable of regenerating NADH when
      methyl isobutyl carbinol was used as a second substrate. Continuous production of
      l-menthol was achieved by using a reactor equipped with a hydrophobic
      microfiltration membrane. It was found that both NAD(H) and the enzyme could be
      retained in the reactor and the products, l-methanol and methyl isobutyl ketone,
      passed through the membrane. The production of l-methanol was maintained for 270
      h at a rate of 46.1 g l-1 d-1, and had decreased by one-half at 607 h. The
      recycling number of NAD(H) was 2500 (max. 3020) during the operation. The number
      of theoretical plates was calculated to be 40 for the separation of l-menthol
      from other reactants.

PMID- 1366552
TI  - Cultivation of mammalian cells in serum-free medium.

PMID- 1366553
TI  - Microrobotics in biotechnology.

PMID- 1366554
TI  - Non-protein engineering: small drug design.

PMID- 1366555
TI  - Capitalizing on carbohydrates.

PMID- 1366556
TI  - The improving prospects for yield increase by genetic engineering in antibiotic
      producing Streptomycetes.
AB  - Molecular genetics has spawned a dramatic expansion of the biotechnology industry
      in the direction of the products of single genes. On the other hand, antibiotics-
      some of the classical products of biotechnology--result from the concerted action
      of many genes, and it is therefore less straightforward to apply the new
      techniques to antibiotic production. Studies of cloned genes for antibiotic
      biosynthesis are now providing information that should allow the application of a
      combination of traditional and recombinant DNA methodology to the improvement of
      yield in antibiotic-producing Streptomyces species.

PMID- 1366557
TI  - Kluyveromyces as a host for heterologous gene expression: expression and
      secretion of prochymosin.
AB  - We have developed the yeast Kluyveromyces lactis as a host organism for the
      production of the milk-clotting enzyme chymosin. In contrast to Saccharomyces
      cerevisiae, we found that this yeast is capable of the synthesis and secretion of
      fully active prochymosin. Various signal sequences could be used to efficiently
      direct the secretion of prochymosin in Kluyveromyces, but not in S. cerevisiae.
      We conclude that the efficient synthetic and secretory capacity of this
      heterologous protein is a property of the yeast Kluyveromyces. These results have
      led to the development of a large scale production process for chymosin.

PMID- 1366558
TI  - New approaches to increase the expression and stability of cloned foreign genes
      in Escherichia coli.
AB  - A family of expression plasmid vectors were constructed by fusing the strong P2
      promoter of the rrnB gene of Escherichia coli (coding for ribosomal RNA) to the
      lac operator, thereby eliminating regulatory sequences from the rrnB gene and
      placing the expression under lac repressor control. This promoter proved to be
      stronger in vivo than the well-known consensus tac promoter, and its strength
      could be further increased by converting the sequence to consensus. The stability
      of the recombinant proteins could be increased by fusion to various lengths of
      the N-terminal end of beta-galactosidase, or by inserting a synthetic
      oligonucleotide, coding for heptathreonine. A new method was developed for the
      stabilization of recombinant plasmids without antibiotic selection, based on the
      presence of an essential gene on the plasmid and its absence from the chromosome.
      The application of this method is illustrated by the example of a plasmid
      expressing human proinsulin.

PMID- 1366559
TI  - Pilot scale production of a heterologous Trichoderma reesei cellulase by
      Saccharomyces cerevisiae.
AB  - Cellobiohydrolase II of Trichoderma reesei was produced in laboratory and pilot
      scale using a transformant strain of Saccharomyces cerevisiae harbouring a
      multicopy expression plasmid. Different strategies were compared for
      concentration and partial purification of the enzyme produced in a 200 1 pilot
      cultivation. After efficient separation of biomass and sub-cellular particulate
      matter, a combination of ultrafiltration and adsorbent treatment for removal of
      protein impurities was used to provide a concentrate for chromatographic
      purification. Effective purification of the CBH II protein was obtained by
      passing the concentrate through a column of DEAE Sepharose, on which almost all
      the yeast proteins were adsorbed. The purified enzyme reacted with antibodies
      prepared against T. reesei CBH II and catalyzed partial solubilization of
      crystalline cellulose to soluble sugars.

PMID- 1366560
TI  - High-level expression of human insulin-like growth factor II in Escherichia coli.
AB  - A gene encoding mature human insulin-like growth factor II (IGF-II) was
      constructed from the modified IGF-II cDNA sequence and two double-stranded
      synthetic oligodeoxynucleotide linkers. It was fused to a truncated lacZ gene
      such that IGF-II was expressed as part of C-terminus of beta-galactosidase. This
      fused lacZ'-IGF-II gene was under the control of tac promoter and we overproduced
      the beta-galactosidase-IGF-II fusion protein in the Escherichia coli. The fusion
      protein formed inclusion bodies inside the cells. The fusion protein was purified
      from the isolated inclusion bodies and IGF-II protein was obtained from their
      fusion protein by CNBr cleavage. The released IGF-II was confirmed by its
      molecular weight as determined by SDS-PAGE and by its ability to bind anti-IGF
      antibody.

PMID- 1366561
TI  - Production of a protein A--lymphotoxin hybrid protein for cancer-targeted
      therapy.
AB  - A hybrid protein between staphylococcal protein A and human lymphotoxin, ALT, was
      produced in Escherichia coli by expression of a recombinant plasmid containing
      the respective genes. IgG-binding activity of ALT was confirmed by Western
      blotting analysis and by affinity purification with IgG-Sepharose column
      chromatography. The purified ALT had cytotoxicity on mouse L-929 cells and its
      specific activity was approximately 3.5-5.0 X 10(6) U mg-1. ALT was partially
      degraded by a protease including in the E. coli lysate or trypsin and was
      converted to lymphotoxin which lacks the NH2-terminal 19 residues but possesses
      higher cytotoxic activity than ALT.

PMID- 1366562
TI  - A method for removal of toxic chromium using dialysis-sac cultures of a chromate
      reducing strain of Enterobacter cloacae.
AB  - A method for removal of toxic hexavalent chromium (chromate: CrO2-4) was
      developed by use of dialysis-sac cultures of a chromate-reducing strain of
      Enterobacter cloacae (HO1). E. cloacae strain HO1 cells were put in dialysis
      (semipermeable membrane) sacs, and the sacs were submerged in water containing
      toxic CrO2-4. The dialysis sacs allowed CrO2-4 to diffuse into the culture, and
      CrO2-4 was reduced anaerobically in the dialysis sacs by the E. cloacae cells.
      Because reduced chromium readily formed insoluble chromium hydroxides in the
      dialysis sacs, the greater part of reduced chromium was unable to diffuse out
      through the semipermeable membrane. Thus the dialysis culture of E. cloacae
      strain HO1 could successfully remove toxic chromium from the surrounding water.
      If the initial concentration of CrO2-4 was less than 4 mM (208 ppm as chromium),
      about 90% of the total chromium could be removed from water by the described
      method.

PMID- 1366563
TI  - Continuous production of baculovirus in a cascade of insect-cell reactors.
AB  - Insect cells (Spodoptera frugiperda) were cultured in a continuous stirred-tank
      reactor. The effluent was led to a cascade of another two reactors, each
      containing half the volume of the cell-growth reactor, where the cells were
      infected with Autographa californica nuclear polyhedrosis virus. For about 10
      days production of 10(7) polyhedra (virus particles embedded in a protein
      capsule) per cm3 was achieved. This short production time compared to previous
      experiments involving an analogous system with a single infection vessel of equal
      volume to the cell-growth vessel is ascribed to the accelerated occurrence of the
      so-called passage effect (a decrease of infectious virus with time). From the
      results of a computer model it was concluded that this passage effect was
      accelerated by the change in residence time distribution as compared to the
      earlier experiments.

PMID- 1366565
TI  - Microelectrode probes for biomedical applications.

PMID- 1366564
TI  - Phenol-induced membrane changes in free and immobilized Escherichia coli.
AB  - Membranes of Escherichia coli cells grown in the presence of phenol were examined
      after isolation of the cytoplasmic and outer membrane fractions. Both membrane
      types showed reduced lipid-to-protein ratios compared to cells grown without
      phenol. Phenol-induced differences in the expression of individual proteins of
      the inner membrane were established. Different proteins of the outer membrane,
      probably involved in the uptake of iron, were expressed in smaller quantities
      after phenol addition. Growth in the presence of phenol increased the respiratory
      activity of the cytoplasmic membrane, whereas the direct inhibition of O2
      consumption by phenol was not affected by the presence of this compound in the
      growth medium. E. coli cells grown entrapped in calcium alginate showed low lipid
      to-protein ratios even without phenol in the growth medium. Immobilization of
      cells also markedly changed the protein pattern of the outer membrane.

PMID- 1366566
TI  - Production of peptides in plant seeds.

PMID- 1366567
TI  - Protein engineering for thermostability.
AB  - Studies with small, monomeric proteins indicate that, to some extent, the effects
      of amino acid substitutions can be predicted. However, conformational and other
      changes may complicate the prediction. Site-directed mutagenesis is leading both
      to a better understanding of protein stability and to the production of more
      stable proteins.

PMID- 1366568
TI  - Vaccinia virus: a versatile tool for molecular biologists.
AB  - Continued advances in genetic engineering have made possible the high-level
      expression of correctly processed cellular, viral and bacterial polypeptides.
      This article focuses on viral expression vectors and, more specifically, the
      vaccinia virus expression system. Vaccinia virus has been used to express a
      variety of proteins with useful immunogenic, catalytic or pharmaceutical
      properties. We discuss briefly the biology of vaccinia and its significance in
      the use of vaccinia as an expression vector, the variety of vaccinia systems
      currently in use and, finally, we summarize some recent developments which bode
      well for future applications of vaccinia virus technology.

PMID- 1366569
TI  - Antibiotics from within: antibacterials from human and animal sources.
AB  - The isolation of potent antibacterial proteins and peptides from human and animal
      phagocytes has raised the possibility that these 'antibiotics from within' can be
      used as therapeutic agents. Problems in delivery to and toxicity towards the host
      must be faced, but rapid progress in defining the structural determinants of the
      cytotoxic action of these naturally occurring cytotoxins provides a basis for
      biotechnological development of new classes of antibiotics.

PMID- 1366570
TI  - Peptide-mediated formation of quantum semiconductors.

PMID- 1366571
TI  - Improvement of wool production through genetic engineering.
AB  - Wool is a natural fibre popular in the manufacture of outer clothing and is a
      vital source of income for several countries. Fundamental knowledge of how wool
      grows has been gained from research on the biology of sheep, and the prospects
      ahead are to take advantage of the development and application of recombinant DNA
      technology to improve the efficiency of production of wool and its quality. This
      review surveys the possibilities for producing transgenic sheep, modifying rumen
      bacteria and forage crops, thus increasing the nutritional benefit sheep gain
      from pasture.

PMID- 1366572
TI  - In vivo bioluminescence: new potentials for microbiology.

PMID- 1366573
TI  - Separation of micro-organisms from meat and their rapid enumeration using a
      membrane filtration-epifluorescent microscopy technique.
AB  - A new method of separating bacteria from beef mince has been developed, in which
      an alkaline protease, Alcalase 0.6 L, was used to degrade the meat proteins,
      leaving micro-organisms in suspension. The organisms were then counted, using a
      membrane filtration-epifluorescent microscopy technique. A correlation
      coefficient of 0.97 was obtained between this method and the standard plate
      count, indicating its suitability for use in quality control.

PMID- 1366574
TI  - Detection and identification of E. coli producing heat-labile enterotoxin type I
      by enzymatic amplification of a specific DNA fragment.
AB  - The polymerase chain reaction (PCR) was used to identify strains of Escherichia
      coli which produce heat-labile toxin type I (LTI). Amplification primers were
      designed to detect E. coli strains of human as well as porcine origin. This assay
      was used to test the ATCC 37218 strain, which carries a recombinant plasmid with
      the genetic information for production of porcine LTI (pLTI). In addition, three
      clinical E. coli isolates of human and one of porcine origin were tested. All
      clinical isolates were reported to produce heat-labile enterotoxin (hLTI and
      pLTI, respectively) when tested by the Y1 adrenal cell method and/or by the CHO
      cell method. All strains yielded the expected 275 bp DNA fragment after enzymatic
      amplification. This fragment was further identified by allele specific
      oligonucleotide hybridization. Alternatively, the fragment was identified by a
      SmaI restriction enzyme site which is present in the genes of both the E. coli
      isolated from humans and pigs. The detection limit determined in water with the
      ATCC 37218 strain was 20 bacteria. The amplified sequence included a CfoI
      polymorphism which allowed to distinguish between the genes coding for pLTI and
      hLTI. All of the strains tested showed this polymorphism as expected. Depending
      on the identification method chosen, SmaI digestion or oligonucleotide
      hybridization, pure water can be analysed within 8 h or 12 h, respectively. This
      method may be adapted to environmental and food samples.

PMID- 1366575
TI  - Influence of glycine betaine on the transfer of plasmid RP4 between Escherichia
      coli strains in marine sediments.
AB  - The conjugative transfer of plasmid RP4 between two strains of Escherichia coli
      in a sterile marine sediment was enhanced by the presence of glycine betaine
      (frequency increased 20 to 40 times). The conjugation was also facilitated by the
      osmoprotection of donor cells. Glycine betaine is a universal osmolyte and has
      been found in marine sediments at high concentrations. So this phenomenon could
      have epidemiological and sanitary importance by increasing the possibility of
      dissemination of some plasmids present in enterobacteria in natural marine
      deposits.

PMID- 1366576
TI  - NADH production from NAD+ with a formate dehydrogenase system involving
      immobilized cells of a methylotrophic Arthrobacter strain.
AB  - A convenient and economical method of NADH production from NAD+ has been
      established using a formate dehydrogenase system involving immobilized cells of a
      methanol-utilizing bacterium. Arthrobacter sp, KM62. Four kinds of cell
      entrapment were studied. An immobilized cell preparation showing a high NADH
      production activity was obtained by entrapment in a kappa-carrageenan gel
      lattice. The NADH-producing activity of the immobilized cells was investigated
      under various conditions. The NADH-producing activity was evoked on the addition
      of Triton X-100 to the reaction mixture. The conditions for the continuous
      production of NADH with an immobilized cell column were also investigated. When a
      reaction mixture containing 10 mumol (6.63 mg) ml-1 NAD+ was passed through the
      column (1.2 x 20 cm) containing 1.62 g (as dry weight) of immobilized cells, at a
      space velocity of 0.125 at 35 degrees C, complete conversion was attained.

PMID- 1366577
TI  - Effective diffusion coefficient of sucrose in calcium alginate gel.
AB  - The effective diffusion coefficient of sucrose in 5% calcium alginate gel
      containing 41.6 g.d.c. l-1. Saccharomyces cerevisiae was investigated. Both free
      and immobilized S. cerevisiae in 0.175 cm and 0.3 cm diameter particles were used
      and the reactions were achieved in a medium containing 100 g l-1 sucrose and 0.05
      M CaCl2. With the assumption that the microorganisms did not grow or die in this
      medium, the results were analyzed according to Michaelis-Menten kinetics and the
      values of the parameters were determined as: Vm = 0.256 g ml-1 gel h-1, Km0 =
      0.097 g ml-1, Km1 = 0.125 g ml-1, and Km2 = 0.165 g ml-1. Using these values,
      effectiveness factors were calculated as eta 1 = 0.89 and eta 2 = 0.76, and
      effective diffusion coefficients for sucrose in calcium alginate gel were
      determined as De1 = 4.1 X 10(-6) cm2 s-1 and De2 = 4.0 X 10(-6) cm2 s-1, for the
      particle size involved.

PMID- 1366578
TI  - Solid phase membrane mimetics: immobilized artificial membranes.
AB  - The studies discussed demonstrate the importance of developing rapid methods to
      purify membrane proteins and also quantitate binding events between cell
      membranes and biomolecules. Traditional equilibrium methods are experimentally
      very difficult because of long equilibration times, peptide aggregation, and the
      need to make several measurements to obtain a single binding constant. We are
      developing chromatographic methods to measure binding constants between membranes
      and biomolecules by using solid phase membrane mimetics. Solid phase binding
      assays are well established for reactions that typically occur in solution,
      whereas for reactions that require a membrane environment, no solid phase assay
      exists. Solid phase membrane mimetics have the potential of filling this gap.

PMID- 1366579
TI  - Patent reports.

PMID- 1366580
TI  - Bioregulatory mechanisms at the level of cell organelle interactions:
      microspectrofluorometric in situ studies.
AB  - The spatiotemporal analysis of bioregulatory mechanisms at the level of
      intracellular multienzyme complexes and organelle interactions is made possible
      by the availability of endogenous and exogenous fluorescence probes, the
      development of microspectrofluorometers allowing one- and two-dimensional scans
      of intracellular fluorescence reactions, and the use of micromanipulatory
      techniques enabling the rapid alteration of metabolic states. Absorbed photons
      are not only a tool for quantitative evaluation of metabolic processes, they can
      also trigger alterations of cell membranes and functions as mediated by
      photosensitizer drugs. In the hierarchy of intracellular organization different
      levels of complexity are accessible to study, such as the regulation of
      multienzyme complexes and the interaction of organelle complexes. Typical
      applications of these methods are the investigation of drug effects (e.g., on
      melanoma cells), metabolic and structural alterations (e.g., in cystic fibrosis
      and Gaucher fibroblasts), organelle interactions in cells treated with toxic
      agents. The implications are relevant to biotechnology for better control of
      metabolite production and processing, design and testing of new drugs,
      understanding of drug resistance and better targeting of drugs or probes to
      selected intracellular sites. In addition, such in vitro methods can contribute
      to the provision of an alternative to "whole animal experiments" as already
      achieved in human and mouse fibroblasts, hepatocytes, hepatoma, Swiss 3T3 cells
      and other cells in culture, especially with regards to an analysis of the action
      of xenobiotics and drugs in cell physiology and pathology, fluorescence recovery
      after photobleaching, study of cytoskeleton dynamics and multiparameter probing
      of organelle activity during in vitro wound repair.

PMID- 1366581
TI  - High level expression of interleukin-1 beta in a recombinant Escherichia coli
      strain for use in a controlled bioreactor.
AB  - A recombinant bacterial strain for the large scale production of human
      interleukin-1 beta (IL-1 beta) was constructed. The lambda Pr and the tryptophan
      systems were compared for efficiency of transcription and regulation. The
      efficiency of IL-1 protein production from these constructs was analyzed.
      Enhanced protein synthesis was achieved by the fusion of lambda Pr promoter
      sequences with trp leader sequences which included the trp RBS. A strain (JM101)
      was selected for use as a host and tested in a one liter bioreactor. A growth and
      induction regimen was established for use in bioreactors which results in the
      accumulation of 0.75-0.95 g l-1 of recombinant IL-1.

PMID- 1366583
TI  - A new cyclodextrin-agar medium for surface cultivation of microbes on lipophilic
      substrates.
AB  - Inclusion of cyclodextrins into an agar gel enabled a homogeneous incorporation
      of water-immiscible lipophilic organic liquids and solids as substrates for
      surface microbial growth or conversion. Surface cultivation of Candida lipolytica
      and C. tropicalis was demonstrated in alpha- and beta-cyclodextrin/hexadecane
      agar media.

PMID- 1366582
TI  - Simultaneous regulation of plasmid replication and heterologous gene expression
      in Escherichia coli.
AB  - An expression plasmid in which plasmid DNA replication and heterologous gene
      expression can be simultaneously regulated was constructed to avoid derepression
      prior to induction. This was achieved by placing a pBR322 origin of replication
      immediately downstream of an anthranilate synthase-human epidermal growth factor
      fusion gene (trpE-hEGF), both under the control of the promoter from the
      tryptophan biosynthetic operon. Regulation of plasmid copy number ensured tight
      repression of the trp promoter prior to induction. Upon induction, plasmid copy
      number increased up to six-fold and the fusion protein accumulated to
      approximately 12% of total cell protein. Induction experiments with a series of
      plasmid derivatives with sequentially lower copy numbers revealed that
      accumulation levels of the TrpE-hEGF fusion protein post-induction correlated
      well with plasmid copy number. Plasmid constructs where the native trp promoter
      had been replaced by derivatives deleted of the attenuator resulted in high
      levels of hEGF accumulation in the tryptophan-free medium prior to induction.
      Nevertheless, up to two-fold increase in TrpE-hEGF accumulation levels were
      obtained using the constructs lacking the attenuator compared to those bearing
      the native trp promoter.

PMID- 1366585
TI  - The use of tissue culture for the detection of mycotoxins.
AB  - After incubation with 20 different mycotoxin standards and extracts from fungi
      and feed stuffs, fluorescent flow cytometry was used to measure viability of NS-1
      cells and compared to microscopic assessment of cytotoxicity on stained HEp-11
      monolayers. Both methods gave essentially the same results but the cytometric
      analysis offered a more quantitative approach and was particularly appropriate in
      the screening of extracts containing fats. The potential uses of a cytotoxic test
      in the analysis of feed stuffs and fungal extracts for the presence of mycotoxins
      are discussed.

PMID- 1366584
TI  - An appraisal of bioassay methods for the detection of mycotoxins--a review.
AB  - The literature on bioassay methods for mycotoxin detection has been reviewed. An
      outline of the range of bioassay methods is given and the role of cytotoxicity
      tests in particular has been emphasized.

PMID- 1366586
TI  - Development of an optimized system for electroporation of Listeria species.
AB  - Electroporation was used to facilitate transformation of Listeria species with
      plasmid DNA. Optimal conditions for transformation of L. monocytogenes were a
      field strength of 8.5 kV/cm, 200 Ohms resistance, 25 microF capacitor with a time
      constant of 5 ms. With these conditions, 3.9 x 10(6) transformants/micrograms DNA
      were obtained. Under the same conditions, L. innocua and L. ivanovii exhibited a
      frequency of transformation similar to that of L. monocytogenes but a somewhat
      lower level was obtained with L. seeligeri.

PMID- 1366587
TI  - An improved method for rapid isolation of plasmid DNA from wild-type gram
      negative bacteria for plasmid restriction profile analysis.
AB  - An improved method for the isolation of large and small plasmids from wild-type
      Gram-negative bacteria has been developed. The protocol combines the lysis and
      purification procedures of two popular plasmid isolation methods, and produces
      DNA sufficiently pure for restriction enzyme digestion in less than three hours.

PMID- 1366588
TI  - Cell culture standards--time for a rethink?

PMID- 1366589
TI  - Animal cells--the breakthrough to a dominant technology.

PMID- 1366590
TI  - Tissue culture in the study of cancer.

PMID- 1366591
TI  - Stimulation of proliferation and immunoglobulin M production by lactoferrin in
      human-human and mouse-mouse hybridomas cultures in serum-free conditions.
AB  - The effects of growth factors, such as insulin, transferrin, lactoferrin,
      ethanolamine, and selenium, on proliferation and IgM production of human-human
      hybridomas HB4C5 cells in a serum-free enriched RDF (eRDF) medium were studied.
      Among them, lactoferrin markedly stimulated proliferation and IgM production of
      the cells. Another iron-binding protein, transferrin, stimulated proliferation of
      HB4C5 cells as well as lactoferrin, but its stimulatory effect on IgM production
      was negligible. The proliferation and IgM production of HB4C5 cells gave some
      detectable delays in conventional ITES-eRDF medium at low cell densities, but the
      delays were avoided by the addition of lactoferrin. However, eRDF medium
      supplemented with lactoferrin could not support proliferation and IgM production
      of the cells at high cell densities. For proliferation and IgM production of
      HB4C5 cells, eRDF medium supplemented with 25 micrograms/ml lactoferrin, 10
      microM ethanolamine, 35 micrograms/ml transferrin, and 2.5 nM selenium (LETS
      eRDF) gave the best result. Lactoferrin stimulated proliferation of human-human
      and mouse-mouse hybridomas producing IgG or IgM, but stimulation of Ig production
      was detected only in IgM producers. These results suggest that cell
      proliferation, IgM production, and IgG production of hybridomas are regulated by
      different mechanisms.

PMID- 1366592
TI  - Expression of human beta-interferon in Namalwa KJM-1 which was adapted to serum
      free medium.
AB  - A Namalwa cell line, KJM-1, which was adapted to serum-free medium is thought to
      be a very useful host cell line for recombinant DNA technology. Thus, the utility
      of Namalwa KJM-1 for expression of foreign genes was examined. As a model system
      human beta-interferon (beta-IFN) gene was engineered for expression in this cell
      line. For construction of the beta-IFN expression vector pSE1 beta 1-4, the
      expression vector pAGE107 was constructed and used. It contains simian virus 40
      (SV40) early promoter, the rabbit beta-globin RNA processing signals for splicing
      and polyadenylation, and SV40 early RNA processing signal for polyadenylation. In
      addition to the above transcription unit, pAGE107 contains the ampicillin
      resistance gene and G418-resistance gene. They can confer ampicillin resistance
      to Escherichia coli (E. coli) and G418 resistance to animal cells. To introduce
      plasmid DNA into cells, electroporation is a useful method (Wong, 1982; Potter,
      1984). We have established conditions for DNA-mediated transfection of Namalwa
      KJM-1 cell line by electroporation. Among pSE1 beta 1-4-introduced cells, clone 1
      3 was further examined for the expression of beta-IFN in serum-free medium. The
      production level of beta-IFN was elevated with the increase of the cell density.
      The results indicated that the Namalwa KJM-1 cell line is useful for production
      of foreign gene products.

PMID- 1366593
TI  - Rapid in vitro transformation system for liver epithelial cells by iron chelate,
      Fe-NTA.
AB  - We have previously found toxic effects of iron chelate, Fe-NTA on cultured normal
      rat liver epithelial cells (RL34). In the present study, when RL34 cells were
      exposed to 50 micrograms/ml iron of Fe-NTA for 15 days, besides the expected
      cytolytic effects in most cells, the appearance of resistant cells was observed.
      The resistant cells showed drastic morphological transformation, grew in soft
      agar, and induced hepatocellular carcinomas when transplanted into syngeneic
      newborn rats in a short period of time. Since DNA instability in the transformed
      cells was ascertained by differential AO staining, it is suggested that DNA
      damage by Fe-NTA is of a critical importance for extremely rapid neoplastic
      transformation of normal epithelial cells.

PMID- 1366594
TI  - A novel acid proteinase released by hybridoma cells.
AB  - An acid proteinase has been detected in culture supernate of the 9.2.27 murine
      hybridoma. This enzyme extensively degrades albumin and transferrin during short
      incubations at pH 3 and below. Limited proteolysis of the 9.2.27 IgG2a appears to
      occur in the culture supernate. Proteolysis in enhanced at low pH in the presence
      of urea or 1 M acetic acid. The proteinase activity accumulates in continuous
      perfusion, total cell recycle cultures, beginning during exponential growth of
      the hybridoma. It is destroyed by boiling and blocked by pepstatin, but not by
      inhibitors of cysteine or serine proteinases or by EDTA. The low pH optimum may
      distinguish this enzyme from the known rat and mouse aspartic acid proteinases
      including cathepsin D and cathepsin E.

PMID- 1366595
TI  - Evaluation of mitochondrial content and activity with nonyl-acridine orange and
      rhodamine 123: flow cytometric analysis and comparison with quantitative
      morphometry. Comparative analysis by flow cytometry and quantitative morphometry
      of mitochondrial content and activity.
AB  - Mouse fibroblasts 3T3.4E and two cells lines obtained by fusion (3T3.4E cells x
      normal human keratinocytes), (3T3 x NHK), and (3T3.4E cells x hand wart
      keratinocytes), (3T3 x HWK), were compared for mitochondrial activity and content
      between 5 and 20 days of culture, from the 16th to 20th passage, by using Rh 123
      and NAO respectively. In 3T3.4E cells both Rh 123 and NAO fluorescence were
      similar after 5 and 7 days of culture, indicating no modification of
      mitochondrial activity and content at that time. However, in cells derived from
      fusion of 3T3 x NHK or 3T3 x HWK, Rh 123 increased from 5 to 20 days whereas NAO
      fluorescence was maximal at 7 days of culture and then decreased, indicating that
      their mitochondrial activity differed from that of 3T3.4E cells. No difference
      was observed between the 16th and 20th passage. Quantitative morphometry and flow
      cytometry gave good correlations at 7 days of culture for the cell size,
      estimated either by the cell area or the cell diameter, and for mitochondria
      content, evaluated either by the number of mitochondria per cell or NAO
      fluorescence intensity.

PMID- 1366596
TI  - Purification and characterization of immunoglobulin production stimulating factor
      derived from human B lymphoblastoid HO-323 cells.
AB  - An immunoglobulin (Ig) production stimulating factor (IPSF) for hybridomas was
      found in spent medium of the human B lymphoblastoid cell line, HO-323. The IPSF
      was purified by serial use of DEAE chromatography, ultrafiltration, gel
      filtration and HPLC-DEAE chromatography. Purified IPSF was estimated to be a 410
      k macro molecule by gel filtration, and contained three types of isomers which
      were separated from each other by native polyacrylamide gel electrophoresis. All
      of the isomers were, however, assumed to have the same protein components by SDS
      polyacrylamide gel electrophoresis. The IPSF was effective for human-human and
      mouse-mouse hybridomas producing IgM, but not for IgG producers in the
      experimental condition used here. Human-human hybridoma HF10B4, cultured in IPSF
      containing medium, produced 20 times more IgM than in IPSF-free medium under
      serum-free conditions. The IPSF showed very little proliferation stimulating
      activity on HF10B4 cells.

PMID- 1366597
TI  - Concepts of electrically connecting redox enzymes to metal electrodes.

PMID- 1366598
TI  - Macromolecule structure determination using NMR data and molecular simulation
      techniques.
AB  - NMR graf utilizes molecular mechanics and molecular dynamics simulation
      techniques, in conjunction with NOE and J-coupling data from NMR experiments, to
      quickly derive and analyze candidate structures of macromolecules. Test cases
      produce results within the experimental error bars of structures derived using x
      ray crystallography.

PMID- 1366599
TI  - Optimization in preparative liquid chromatography.

PMID- 1366600
TI  - Finally, a KISS* program for computer aided chromatography.

PMID- 1366601
TI  - Interaction of auxin with dibasic amino acids.
AB  - Auxin interacts with dibasic amino acids forming charge-transfer complexes. The
      interaction is of hydrophilic character, the strength of interaction increasing
      with the logarithm of auxin concentration. Sodium, potassium, magnesium and
      calcium ions decrease the strength of interaction, while their inhibitory effect
      increases with increasing concentration and ion charge.

PMID- 1366602
TI  - Isolation and characterization of a lectin from the seeds of Dioclea lehmanni.
AB  - Affinity chromatography of the globulin fraction from the seeds of Dioclea
      lehmanni on Sephacryl S-200 yielded two lectins, one slightly retarded and
      another strongly bound. The latter, which was a glucose/mannose specific lectin,
      was purified and the following properties were determined: pI, Mr of subunits,
      carbohydrate content, A, aminoacid composition, hemagglutination and inhibition
      patterns, N-terminal sequence and mitogenic activity. These properties of the
      lectin were very similar to those of the Con A and Dioclea grandiflora lectins.

PMID- 1366603
TI  - Cardiac glycosides of Beaumontia brevituba and B. murtonii.
AB  - Cardiac glycosides from Beaumontia brevituba and B. murtonii were examined.
      Gentiobiosyl-beta-D-cymaroside and gentiobiosyl-alpha-L-cymaroside of
      digitoxigenin were isolated from the seeds, unripe fruits, and leaves of B.
      brevituba, and the leaves of B. murtonii. Oleandrigenin and/or delta 16
      digitoxigenin glycosides having the same sugar moieties were not isolated from
      the leaves of B. brevituba but from the leaves of B. murtonii as well as the
      seeds of B. brevituba.

PMID- 1366604
TI  - Feruloylated xyloglucan and p-coumaroyl arabinoxylan oligosaccharides from bamboo
      shoot cell-walls.
AB  - A novel feruloylated xyloglucan disaccharide and p-coumaroylated arabinoxylan
      trisaccharide were isolated from cell walls of growing bamboo (Phyllostachys
      edulis) shoots. On the basis of chemical and spectral data, their structures were
      determined to be O-(4-O-trans-feruloyl-alpha-D- xylopyranosyl)-(1----6)-D
      glucopyranose and O-[5-O-(trans-p-coumaroyl)- alpha-L-arabinofuranosyl]-(1----3)
      O-beta-D-xylopyranosyl-(1----4)-D- xylopyranose, respectively. This is the first
      reported evidence of a phenolic acid covalently associated with the cell wall
      hemicellulose, xyloglucan.

PMID- 1366606
TI  - Calcium-responsive expression of plasmid-mediated outer membrane proteins from
      Yersinia enterocolitica grown on solid media.
AB  - In vitro synthesis of proteins directed by Yersinia enterocolitica virulence
      plasmid DNA was studied using a cell-free Escherichia coli coupled transcription
      translation system. Out of a total of twenty-four polypeptides synthesized in
      vitro, ten were identified (based on virtually identical molecular masses) as
      outer membrane proteins synthesized in vivo when virulent plasmid-bearing Y.
      enterocolitica cells were grown on four different solid media. Two high molecular
      weight outer membrane proteins synthesized in vivo by plasmid-bearing cells were
      not detected in the in vitro protein synthesizing system. Different plasmid
      mediated outer membrane proteins were expressed in vivo in Y. enterocolitica
      grown on different media. Y. enterocolitica grown on media with high calcium
      concentration (1.4-1.5 mM) expressed twice the number of lower molecular weight
      outer membrane proteins than the organism grown on low calcium (238-311 microM)
      media. This is the first report that a single serotype has been shown to
      synthesize all the reported virulence plasmid-encoded outer membrane proteins
      including three new polypeptides. The constituents in the medium as well as the
      level of calcium appeared to have a regulatory role in plasmid gene expression
      for lower molecular weight outer membrane proteins.

PMID- 1366605
TI  - Production of Streptomyces clavuligerus isopenicillin N synthase in Escherichia
      coli using two-cistron expression systems.
AB  - Streptomyces clavuligerus isopenicillin N synthase (IPNS) gene expression was
      achieved in Escherichia coli by the construction of two-cistron expression
      systems formed in the high copy number plasmid vector pUC119. These two-cistron
      constructions were composed of the IPNS gene and its flanking sequences which
      encoded an upstream open reading frame (ORF), the IPNS ribosome binding site and
      a putative transcription terminator. No E. coli- like Streptomyces promoter motif
      was present upstream of the IPNS gene therefore transcriptional regulation of the
      two-cistron system was provided by the lac promoter of pUC119. Enzymatically
      active IPNS was detected in E. coli cells harboring the recombinant plasmids
      thereby providing evidence for the activity of the IPNS ORF and for the
      feasibility of production of S. clavuligerus IPNS in E. coli. These results
      indicate that simple two-cistron constructions involving foreign gene flanking
      sequences may be used to express foreign proteins in E. coli.

PMID- 1366608
TI  - Improvement of production, assay and purification of streptavidin.
AB  - The production of streptavidin by Streptomyces avidinii in several different
      media was examined at 24, 48 and 72 hours. Flask studies indicated that
      fermentation media containing either complex or multiple carbon sources resulted
      in higher yields of streptavidin than media with a single carbon source.
      Streptavidin could be detected in crude fermentation broths by use of a tritiated
      biotin binding assay. This assay appears to give useful estimates of streptavidin
      production. Depending upon the medium employed, streptavidin yields ranged from
      0.5 mg/l to 53 mg/l. Production was successfully scaled up to ten liter
      fermentors. Streptavidin was purified in a one step process from centrifuged,
      concentrated fermentation broths by binding the protein to an iminobiotin column
      at pH 11 followed by elution at pH 4.0. Recovery percentages varied depending
      upon the solubility of the fermentation media ingredients.

PMID- 1366607
TI  - Cytoplasmic and periplasmic expression of a highly basic protein, human
      interleukin 4, in Escherichia coli.
AB  - Human IL-4 (hIL-4) has been cloned from a human T cell line based on its homology
      to the murine IL-4 cDNA sequence. We have compared cytoplasmic and extra
      cytoplasmic expression of this basic protein in Escherichia coli using various
      combinations of promoters, replicons and host strains. Strains producing a
      cytoplasmic product were most successful at heterologous protein expression,
      producing up to 500 mg/l of an inactive aggregated form of the protein. The
      biological activity of the protein could be restored by refolding the protein
      with guanidine hydrochloride and glutathione giving a specific activity identical
      to that of IL-4 derived from CHO cell lines stably transformed with an hIL-4
      expression plasmid. Strains designed to secrete human IL-4 into the periplasmic
      space produced far less protein (approximately 5 mg/l). However, a significant
      fraction of this protein was detected in the culture medium. This fraction
      appeared to be soluble after ultracentrifugation, and demonstrated high specific
      activity without refolding. Leakage of heterologous protein into the culture
      medium may be a viable way to recover biologically active products without
      relying on the denaturation and refolding in vitro that can, at times, yield
      incorrectly folded gene product.

PMID- 1366609
TI  - The effect of neutral resins on the fermentation production of rubradirin.
AB  - Rubradirin is an antibiotic of complex chemical structure which is active vs.
      methicillin resistant staphylococci. Its development has been limited due to
      inadequate production yields. The incorporation of neutral resins into
      fermentations of Streptomyces achromogenes v. rubradiris, UC 8051 resulted in the
      enhanced production of rubradirin. Resins HP-20, HP-21, XAD-2, XAD-7 and XAD-16
      were employed in flask and tank fermentations. The incorporation of these resins
      promoted 2- to 4-fold enhancements of the rubradirin activity produced in flask
      fermentations, and the incorporation of XAD-16 and HP-21 into tank fermentations
      promoted production titer increases greater than 5 fold.

PMID- 1366610
TI  - New strategies for the design of catalytic antibodies.
AB  - A new approach is advanced which is aimed at expanding the scope of antibody
      catalysis. It entails the design and synthesis of haptens that will elicit
      antibodies to catalyze acyl transfer reactions by a methodology which we term
      "bait and switch" catalysis. What we have done involves the placement of a point
      charge on the hapten in close proximity to, or in direct substitution for, a
      chemical functional group we wish to transform in the respective substrate. The
      haptenic charge should induce a complementary charge (on an amino acid residue)
      at the binding site. The substrate will lack this charge but will retain a
      similar overall structure. The monoclonal antibodies that bind these substrates
      now have the potential to act as general acids/bases for substrates having
      hydrolyzable functional groups.

PMID- 1366611
TI  - Genetic engineering of polysaccharide structure: production of variants of
      xanthan gum in Xanthomonas campestris.
AB  - Xanthan gum is an extracellular heteropolysaccharide produced by the bacterium
      Xanthomonas campestris. Xanthan has wide commercial application as a viscosifier
      of aqueous solutions. Previously, through genetic engineering, a set of mutants
      defective in the xanthan biosynthetic pathway has been obtained. Certain mutants
      were shown to synthesize and polymerize structural variants of the xanthan
      repeating unit and thus produce "variant xanthans". Initial studies of solution
      viscosities of these polymers, presented here, indicate that the variants have
      rheological properties similar to, but not identical with, xanthan. These results
      indicate that acetylation and pyruvylation can affect the viscometric properties
      of xanthan. Specifically, the presence of pyruvate increases viscosity, whereas
      acetate decreases viscosity. In addition, the elimination of sugar residues from
      xanthan side chains also has a major effect on viscosity. Compared to wild-type
      xanthan, polymer lacking the terminal mannose (polytetramer) is a poor
      viscosifier. In contrast, polymer lacking both the terminal mannose and
      glucuronic acid (polytrimer) is a superior viscosifier, on a weight basis. There
      is a negative effect of acetylation on the viscosity of polytetramer xanthan, but
      there is seemingly no effect of acetylation on polytrimer xanthan viscosity. The
      further study of these materials should provide insight into the relationship
      between xanthan structure and rheological behavior.

PMID- 1366612
TI  - Chemical and biosynthetic approaches to the production of novel polypeptide
      materials.
AB  - Three approaches to the synthesis of the repetitive copolypeptide [(GlyAla)3
      GlyProGlu]n (1) are described. Direct chemical synthesis of 1 via classical
      solution methods required 18 steps and afforded a polydisperse product with an
      average molecular weight of less than 10,000. Two alternative genetic strategies
      were also explored. In the first, chemically synthesized DNA oligomers were self
      ligated to produce a population of multimers, which were fitted with
      translational start and stop signals and inserted into an expression plasmid
      containing the lambda PL promoter and a synthetic ribosome binding site.
      Transformation of E. coli led to the isolation of a stable recombinant plasmid
      carrying an insert encoding 12 repeats of sequence 1. Attempts to identify
      polypeptide 1 after induction of transformed cultures were unsuccessful. A second
      strategy, generating a tripartite derivative of sequence 1 carrying short N- and
      C-terminal extensions, afforded excellent yields of product. The relative merits
      of chemical and genetic approaches to repetitive polypeptide materials are
      discussed.

PMID- 1366613
TI  - Genetic engineering of structural protein polymers.
AB  - Genetic and protein engineering are components of a new polymer chemistry that
      provide the tools for producing macromolecular polyamide copolymers of diversity
      and precision far beyond the current capabilities of synthetic polymer chemistry.
      The genetic machinery allows molecular control of chemical and physical chain
      properties. Nature utilizes this control to formulate protein polymers into
      materials with extraordinary mechanical properties, such as the strength and
      toughness of silk and the elasticity and resilience of mammalian elastin. The
      properties of these materials have been attributed to the presence of short
      repeating oligopeptide sequences contained in the proteins, fibroin, and elastin.
      We have produced homoblock protein polymers consisting exclusively of silk-like
      crystalline blocks and elastin-like flexible blocks. We have demonstrated that
      each homoblock polymer as produced by microbial fermentation exhibits measurable
      properties of crystallinity and elasticity. Additionally, we have produced
      alternating block copolymers of various amounts of silk-like and elastin-like
      blocks, ranging from a ratio of 1:4 to 2:1, respectively. The crystallinity of
      each copolymer varies with the amount of crystalline block interruptions. The
      production of fiber materials with custom-engineered mechanical properties is a
      potential outcome of this technology.

PMID- 1366614
TI  - Use of immobilized microbial membrane fragments to remove oxygen and favor the
      acetone-butanol fermentation.
AB  - Oxygen-reducing membrane fragments obtained from Escherichia coli were used with
      Clostridium acetobutylicum (C. acetobutylicum) to provide an oxygen-free
      microenvironment for the conversion of glucose to acetone, butanol, and ethanol
      (ABE). The batch fermentation of suspended C. acetobutylicum NRRL-B-643 and its
      ability to produce solvents in the presence of membranes as the oxygen
      elimination agent are described and compared with the conventional sparging
      technique used to maintain anaerobiosis. The use of membrane fragments to remove
      oxygen for fermentation by C. acetobutylicum was successful and gave slightly
      improved results over the use of sparing with regard to lag, biomass, and solvent
      production (e.g., final butanol concentration of 3.25 and 2.7 g/L, respectively).
      Solvent production is also reported for a continuous columnar reactor with
      coimmobilized cells and membranes in kappa-carrageenan gel beads and air
      saturated liquid feed.

PMID- 1366615
TI  - Production of monoclonal antibodies by hybridoma cells in a flat sheet membrane
      bioreactor.
AB  - The purpose of this study was to investigate hybridoma growth and monoclonal
      antibody formation in a flat sheet membrane bioreactor. The effects of several
      different molecular weight cutoff membranes on growth and antibody formation were
      investigated. Nutrient and toxic product diffusion through the membranes were
      quantified, and the kinetic and physical constants of the system were determined.

PMID- 1366617
TI  - Getting the best from plants.

PMID- 1366616
TI  - Enhanced antibody production at slowed growth rates: experimental demonstration
      and a simple structured model.
AB  - A simple structured model for monoclonal antibody (MAb) production kinetics was
      formulated by combining the cell cycle theory with the estimated number of MAb
      coded messenger RNA (mRNA) molecules per cell: it is assumed that the rate
      controlling step is first order in this mRNA and that the growth rate variation
      does not alter the MAb synthesis rate within any cycle phase but only changes the
      relative time length of the individual phases. The model predicted "negatively
      growth associated" MAb production kinetics and thus an enhanced MAb production
      rate to be achieved by slowing the cell growth. Experiments consistent with these
      assumptions provided support for the model. Hybridoma cultures where growth was
      slowed by either a DNA synthesis inhibitor (thymidine or hydroxyurea) or by a
      selective inhibitor of initiation of nonantibody protein (potassium acetate)
      exhibited 50-130% MAb production rate enhancement for growth slowed up to 50%;
      however, further decreases in the growth rate also decreased the MAb production
      rate. Experiments inconsistent with these assumptions showed other behavior:
      general inhibition of protein chain elongation (by cycloheximide) or inhibition
      of ribosomal RNA (rRNA) synthesis (by actinomycin D) each slowed both growth and
      the specific MAb production rate, leading to net "positive" growth associated MAb
      production rates. Thus, a need for models with greater structure is also
      demonstrated.

PMID- 1366618
TI  - Scanning tunnelling microscopy in biotechnology.
AB  - The scanning tunnelling microscope (STM) is capable of atomic resolution of
      highly conductive materials. Whether biological molecules can be visualized to
      the same extent remains an open question, but remarkable progress in the past
      year confirms the possibility of seeing the fine structure of nucleic acids,
      proteins, membranes and viruses, and provides evidence that their dynamic
      interactions can be monitored under conditions approximating to those of the
      native environment.

PMID- 1366619
TI  - Fiber optic evanescent wave immunosensors for medical diagnostics.
AB  - Immunodiagnostic sensors permit sensitive measurement of a wide variety of both
      high and low molecular mass analytes--serum analytes may be detected at picomolar
      concentrations. Due to the sensor monitoring antigen--antibody reactions
      directly, quantitative results are available within seconds to minutes of sample
      introduction. In recent years, the trend has been for immunodiagnostics to be
      used at sites away from centralized medical laboratories. Specific requirements
      associated with such use are being achieved by the development of optical devices
      incorporating evanescent wave sensors.

PMID- 1366620
TI  - Mechanisms of mRNA decay.

PMID- 1366621
TI  - The in vivo application of ribozymes.

PMID- 1366622
TI  - RNA enzymes (ribozymes) as antiviral therapeutic agents.
AB  - Among the landmark discoveries of recent years are ribozymes, RNA molecules which
      possess enzymatic, self-cleaving activities. The concept of exploiting the
      ribozyme catalytic center for cleaving (inactivating) a specific RNA transcript
      is now emerging as a potential therapeutic or preventative strategy in human
      diseases, veterinary medicine and agriculture. Linked to the catalytic center of
      the ribozyme are RNA sequences which are complementary to, and thus serve to
      target the ribozyme to, a unique RNA sequence. Specific association of the
      ribozyme with its target via base pairing, cleavage of the RNA substrate and
      subsequent recycling of the ribozyme make these catalytic RNA molecules
      attractive as antiviral agents. Theoretically, ribozymes can be adapted for the
      destruction of any RNA species, whatever its origin.

PMID- 1366623
TI  - Phosphate control sequences involved in transcriptional regulation of antibiotic
      biosynthesis.
AB  - The expression of genes encoding enzymes involved in antibiotic and other
      secondary metabolite biosynthesis is down-regulated by easily assimilable
      phosphate, carbon and nitrogen sources. Phosphate control of antibiotic
      production appears to act at the transcriptional level by a mechanism similar to
      that involved in control of phosphatases and other phosphate-regulated enzymes. A
      phosphate control (PC) sequence, strikingly similar to the phosphate control
      (pho) boxes of many bacterial genes, has been isolated from the phosphate
      regulated promoter that controls biosynthesis of the antibiotic candicidin, and
      characterized. From computer analysis of sequence data, PC sequences appear to be
      associated with promoter regions of several phosphate-controlled antibiotic
      biosynthetic genes.

PMID- 1366624
TI  - Immunotoxins: status and prospects.
AB  - Immunotoxins, which are conjugates of cell-binding antibodies and toxins, show
      considerable promise in the treatment of certain cancers. Genetic engineering is
      increasingly being used to refine and modify these conjugates, and it is now
      possible to design, express and purify completely recombinant therapeutic
      molecules.

PMID- 1366625
TI  - Anaerobes at work.

PMID- 1366626
TI  - Emerging tools for discovering drugs.

PMID- 1366627
TI  - Use of a cell recycle reactor to increase production of a proteolysis-susceptible
      peptide secreted from recombinant Saccharomyces cerevisiae.
AB  - Operation of a continuous microbial fermentor with cell recycle can significantly
      reduce degradation-associated loss of a secreted protein product. Under
      continuous fermentation conditions, proteolysis of a recombinant growth hormone
      releasing factor (GRF) analog secreted by S. cerevisiae was first order with
      respect to GRF concentration. The maximal GRF concentration was increased from 5
      mg/l to 30 mg/l by the use of a cell recycle reactor, and volumetric productivity
      was increased more than 10-fold to an average of 10 mg/l-1/h-1. A mathematical
      model shows that increased productivity in the cell recycle reactor results from
      a reduced degradation rate and a shorter residence time of the product in the
      fermentor.

PMID- 1366629
TI  - Hydrodynamic deposition: a novel method of cell immobilization.
AB  - A novel method of cell immobilization is described. The cell support consists of
      ceramic microspheres of approximately 50-75 microns diameter. The spheres are
      hollow, having a wall thickness of 10-15 microns and one entrance (ca. 20 microns
      diameter). The walls are porous with a mean pore size of approximately 90 nm.
      When a cell suspension (of S. cerevisiae) is passed through a column of such
      particles, cells are immobilized. Conditions are devised such that the
      overwhelming majority of cells are held in the central cavity of the support and
      not between the particles. Provided turbulence is avoided, the distribution of
      cells along the column length in the steady state is rather homogeneous. The
      facts that (a) essentially all particles, regardless of orientation, entrap
      cells, and (b) nonporous particles also entrap cells with high efficiency,
      indicate that filtration effects are irrelevant and that heretofore unrecognized
      hydrodynamic forces are alone responsible for the cell immobilization. Cells can
      be immobilized to high biomass densities, while the hydrodynamic properties of
      columns containing such immobilized cells are excellent. We describe an on-line
      electronic method for the real-time measurement of immobilized cellular biomass.
      Cell growth (so recorded) and metabolism continue to occur in such particles at
      high rates. Using the glycolytic production of ethanol by S. cerevisiae as a
      model reaction, volumetric productivities as great as any published are obtained.
      Thus the "lobster-pot effect" or "hydrodynamic deposition" represents a novel,
      promising, and generally applicable method of cell immobilization.

PMID- 1366628
TI  - Characterization and novel purification of recombinant human protein C from three
      mammalian cell lines.
AB  - Human Protein C (HPC), an antithrombotic factor with potential clinical utility,
      is a vitamin K-dependent protein that has several complex post-translational
      modifications. In an effort to define the functional roles of these
      modifications, recombinant HPC (rHPC) was expressed in and characterized from 3
      adenovirus-transformed cell lines. The rHPC in crude culture medium from the 3
      cell lines displayed anticoagulant activities that were either higher, slightly
      lower or much lower than that of plasma HPC. The rHPC from each cell line was
      purified and characterized using a novel, but simple chromatographic method,
      termed "pseudo-affinity", capable of resolving molecules differing by only very
      slight modifications. We demonstrate the critical dependence of full gamma
      carboxylation on the function of this protein. In addition, our data indicate
      that both the gamma-carboxyglutamate and glycosyl contents affect the functional
      activities of rHPC.

PMID- 1366630
TI  - Multiple lignin peroxidases of Phanerochaete chrysosporium INA-12.
AB  - Nine proteins with lignin peroxidase activity were separated from cultures of
      Phanerochaete chrysosporium INA-12 in glycerol as carbon source and non-nitrogen
      limited. Four lignin peroxidase isozymes (4, 5, 8, 9) were purified and
      characterized. Although differences in kinetic parameters could be shown,
      antibody reaction showed homology between isozymes. However, thermal stability
      studied, peptide mapping results, and N-terminal sequence analyses established a
      higher degree of homology between isozymes 4/5 and 8/9 types. Protein
      characterization and kinetic data indicate that lignin peroxidase isozymes 4, 5,
      8, and 9 differ from described isozymes in strain BKM. The higher specific
      activity of lignin peroxidase isozymes in cultures with glycerol than in nitrogen
      starved cultures accounts for the higher lignin peroxidase activity obtained in
      these conditions.

PMID- 1366631
TI  - Production of cellulolytic enzymes by immobilized Sporotrichum thermophile.
AB  - Spores of Sporotrichum thermophile were immobilized in agar, polyacrylamide, and
      sodium alginate to generate in situ mycelium for production of cellulolytic
      enzymes. Immobilized mycelium was considerably less effective than free cells for
      cellulase productivity. Of the three gel types, agar beads proved to be the best
      carrier for the immobilized spores and subsequently generated mycelium. Results
      of repeated batch experiments suggested that the immobilized mycelia could be
      reused but at much reduced efficiency.

PMID- 1366632
TI  - Reductive biotransformations of organic compounds by cells or enzymes of yeast.
AB  - Saccharomyces cerevisiae catalyses the asymmetric reductive biotransformation of
      a variety of compounds containing a carbonyl group or carbon-carbon double bond.
      Oxidoreductases participating in these reactions which have commercial potential
      in biotransformation processes are likely to have relatively broad substrate
      specificity. Important carbonyl reductases falling into this category include
      YADH- and yeast NADP-dependent beta-ketoester reductases. The enoyl reductase
      component of the FAS complex may have a role in asymmetric yeast reduction of
      carbon-carbon double bonds of unnatural substrates. Other nicotinamide-requiring
      oxidoreductases of yeast are also surveyed to rationalize observed
      biotransformations of whole yeast cells in terms of specific enzymes. Genetic and
      protein engineering may enable enzymes to be tailored to accept new substrates. A
      greater understanding of the enzymes and reactions involved will facilitate
      further optimization and exploitation of these catalytic systems in industrial
      processes.

PMID- 1366633
TI  - Kinetic and operational study of a cross-flow reactor with immobilized pectolytic
      enzymes.
AB  - The kinetics and operational behavior of a nylon membrane derivative with
      immobilized pectolytic enzymes in a cross-flow reactor were analyzed. A high
      dependence on the recycling flow rate was observed. A design equation of the
      system has been proposed by taking into account both the shear stress
      deactivation and the control of the external diffusional limitations. Integration
      of the resulting design equation allowed us to study the effect of different
      operational parameters on substrate conversion. The catalytic efficiency of the
      immobilized derivative in a cross-flow reactor showed the highest pectin
      hydrolysis capability when it was compared with two different configurations of
      packed-bed reactors.

PMID- 1366634
TI  - Selective flocculation of nucleic acids, lipids, and colloidal particles from a
      yeast cell homogenate by polyethyleneimine, and its scale-up.
AB  - Nucleic acids, lipid, and colloidal particulate material can be selectively
      flocculated from a yeast cell homogenate by the cationic polymer
      polyethyleneimine (PEI). Flocculation can occur from a crude homogenate, a
      homogenate clarified centrifugally, or by the prior use of sodium tetraborate
      (borax). Flocculation from a homogenate previously clarified by the use of borax
      is best suited for large-scale operation. The supernatant obtained following
      centrifugation is effectively free of nucleic acid, lipid, and particulate
      material with essentially 100% soluble enzyme recovery. Enzyme specific activity
      increases by approximately 45% compared to a zero PEI control.

PMID- 1366635
TI  - Production of a foreign protein product with genetically modified plant cells.
AB  - Plant cells (Nicotiana tabacum) were genetically engineered to produce a foreign
      protein, chloramphenicol acetyltransferase (CAT), and the CAT production from
      suspension cultures was investigated. Suspension cultures were grown in a shake
      flask, a stirred fermenter, and a bubble-column fermenter. The CAT production was
      growth related and the maximum activity was reached during the early stationary
      phase. A 41-day, semicontinuous stirred fermenter run, consisting of five
      sequential batch runs, demonstrated long-term CAT production. Continuous CAT
      production was also accomplished in a bubble-column fermenter at a medium flow
      rate of 3.1 ml h-1, which was equivalent to a dilution rate of 0.25 day-1.

PMID- 1366636
TI  - Mechanical stability and diffusional resistance of a polymeric gel used for
      biocatalyst immobilization.
AB  - The mechanical strength of gelatin gels insolubilized by crosslinking with
      formaldehyde was measured at various gelatin percentages and formaldehyde-to
      gelatin ratios. This property was shown to be related to the characteristic
      sponge-like structure of the insolubilized gelatin gel, a structure that
      unexpectedly is also responsible for the resistance to substrate and product
      diffusion. A comparison between immobilizates of invertase and invertase-active
      yeast cells prepared with different gelatin concentrations showed that the
      enzyme, in contrast to cells, is deeply involved in the gel insolubilization
      process. The catalytic behavior of agar, kappa-carrageenan, alginate, and gelatin
      immobilizates was compared under the same conditions of cell loading.

PMID- 1366637
TI  - Interesterification of phosphatidylcholine with lipases in organic media.
AB  - Lipases were investigated with respect to their ability to catalyse the
      incorporation of fatty acids into phosphatidylcholine (PC) by interesterification
      reactions. The enzymes were dried onto solid support materials and the
      conversions were carried out in water-saturated toluene. Three lipases (two
      fungal and one plant enzyme) had the desired activity; immobilized lipase from
      Mucor miehei (Lipozyme) was the most active enzyme. The Lipozyme-catalysed
      interesterification was selective for the sn-1 position of PC and during 48 h of
      reaction around 50% of the fatty acids in this position were replaced with
      heptadecanoic acid, a fatty acid which was practically absent in the original
      phospholipid. Due to adsorption on the support material and the competing
      hydrolysis reaction the total amount of PC in the reaction solution decreased to
      about 40% of the original amount. Higher interesterification rates were obtained
      with free fatty acids as acyl donors than with fatty acid esters.

PMID- 1366638
TI  - Deamplification and deletion of amplified DNA in Streptomyces lividans and S.
      fradiae.
AB  - Streptomyces lividans arginine auxotrophs which show amplification of a 5.7-kb
      DNA sequence, arose at a very high frequency, varying from 10% to 25% of Cmls
      spores. The amplifiable DNA sequence was shown to be stable over many
      generations. However, treatment of Cmls arg mutants with subinhibitory
      concentrations of antibiotics such as spectinomycin, streptomycin,
      chloramphenicol, thiostrepton and kanamycin, either during sporulation or during
      vegetative growth of mycelia, led to the deletion of the entire amplified DNA
      sequence, including the left and right junction sequences. Depending upon the
      method of antibiotic treatment a reduction in the copy number of the amplified
      DNA was also observed. This reduction in copy number apparently occurred without
      drastically affecting the basic structure of the amplifiable unit of DNA. This
      phenomenon appears to be universal since deamplification and deletion were
      observed also in S. fradiae. Further, spontaneous arg mutants arose at much lower
      frequency from spectinomycin-pretreated Cmls cells compared to untreated cells.
      These arg mutants isolated in the presence of spectinomycin did not show
      amplification of the 5.7-kb sequence. Southern blot analysis using the 5.7-kb
      probe showed that the entire DNA sequence homologous to the amplifiable DNA
      sequence had been deleted.

PMID- 1366639
TI  - Regulated overproduction and secretion of yeast carboxypeptidase Y.
AB  - Carboxypeptidase Y (CPY) is a glycosylated yeast vacuolar protease used
      commercially for synthesis of peptides. To increase the production of CPY in
      Saccharomyces cerevisiae we have placed its coding region (PRC1) under control of
      the strongly regulated yeast GAL1 promoter on multicopy plasmids and introduced
      the constructs into vpl1 mutant strains. Such mutants are known to secrete CPY.
      High levels of CPY production were obtained by induction of the GAL1 promoter
      when the cells had left the exponential phase, resulting in a growth-phase
      dependent CPY production similar to that of cells with PRC1 under the control of
      its own promoter. Introduction of a high copy number 2 mu-URA3-LEU2d plasmid with
      GAL1p-PRC1 fusion in a vpl1 strain resulted in a 200-fold increase of secreted
      CPY (about 40 mg/l) as compared to a vpl1 mutant carrying a single copy of the
      wild-type PRC1 gene. The overproduced, secreted CPY was active and had the normal
      N-terminal sequence. Sodium dodecyl sulphate polyacrylamide gel electrophoresis
      revealed two forms of active CPY, probably due to different levels of
      glycosylation.

PMID- 1366640
TI  - Early stages in biofilm development in methanogenic fluidized-bed reactors.
AB  - Biofilm development in methanogenic fluidized-bed reactors with sand as the
      carrier was studied on a laboratory scale. The microorganisms present in
      consecutive layers of the biofilm of mature sludge granules were preliminarily
      characterized on the basis of their morphology, element composition and adhesion
      capacity and were compared to bacteria which take part in the initial
      colonization of sand. The early phase of biofilm development was monitored with
      reactors receiving waste-waters containing different mixtures of volatile fatty
      acids and inoculated with fluidized-bed reactor effluent for different lengths of
      time. The results obtained indicate that facultative anaerobic bacteria
      abundantly present in the outermost biofilm layers of mature sludge granules are
      probably the main primary colonizers of the sand. Methanothrix spp. or other
      methanogens were rarely observed among the primary colonizers. The course of
      biofilm formation was comparable under the various start-up conditions employed
      including variations in waste-water composition, inoculation and anaerobicity.
      However, omission of waste-water and thus of substrate resulted in rapid wash-out
      of the attached biomass.

PMID- 1366642
TI  - Antarctic biotechnology--what is the potential?

PMID- 1366641
TI  - Characteristics and N-terminal amino acid sequence of a manganese peroxidase
      purified from Lentinula edodes cultures grown on a commercial wood substrate.
AB  - Extracellular culture filtrates from ligninolytic cultures of the lignin
      degrading basidiomycete Lentinula (syn. Lentinus) edodes (Berk.) Pegler contained
      one major peroxidase when grown on a commercial oak-wood substrate. The
      peroxidase was purified by polyethylenimine clarification, anion-exchange
      chromatography, and hydrophobic-interaction HPLC. The enzyme (MnP1) was a heme
      iron protein with an apparent molecular weight of 44,600 on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis gels and an isoelectric point of pH
      3.2. The native enzyme had an absorption maximum at 407 nm, which shifted to 420
      nm upon H2O2 addition. The pyridine-hemochrome-absorption spectrum indicated that
      one heme group was present per enzyme as protoporphyrin IX. N-Terminal amino acid
      sequencing showed that MnP1 had higher sequence homology with manganese
      peroxidases than with lignin peroxidases reported from Phanerochaete
      chrysosporium. L. edodes MnP1 was capable of oxidizing lignin and lignin-model
      compounds in the presence of manganese and H2O2.

PMID- 1366643
TI  - Nuclear magnetic resonance (NMR) spectroscopy: applications to protein structure
      and engineering.
AB  - High-resolution nuclear magnetic resonance (NMR) spectroscopy has developed into
      a powerful method for determining the complete three-dimensional structures of
      proteins in solution. This article reviews current applications of this
      technique, with particular emphasis on areas of relevance to biotechnology,
      including protein engineering and protein design.

PMID- 1366644
TI  - Mammalian cell culture at the University of New South Wales.

PMID- 1366645
TI  - Applications of cell culture technology at Commonwealth Serum Laboratories.

PMID- 1366646
TI  - Studies on hybridoma and insect cells in suspension culture.
AB  - Our laboratory has over a period of four years conducted extensive research into
      the metabolism and batch, fed-batch, continuous, perfusion and serum-free culture
      of hybridomas with a view to increasing the productivity of these animal cell
      lines. A brief overview of this work and future plans will be presented here. In
      addition an overview of our more limited work on the Baculovirus expression
      system using insect cell culture, begun during 1989, will also be given.

PMID- 1366647
TI  - Kinetic studies of monoclonal antibody production.

PMID- 1366648
TI  - Animal cell culture in Australia.

PMID- 1366650
TI  - Cell culture standardization and reference cell lines.

PMID- 1366649
TI  - Biotechnology regulation update.

PMID- 1366651
TI  - What should be focused in the study of cell culture technology for production of
      bioactive proteins.

PMID- 1366652
TI  - High density microcarrier culture with a new device which allows oxygenation and
      perfusion of microcarrier cultures.
AB  - A novel system useful for aeration and cell retention in continuous perfused
      microcarrier cultures is described. The system is based on a vibrating cage that
      separates cells and microcarriers from the oxygenation chamber and allows gas
      bubble free oxygen transfer. In the cultivation of monkey kidney cells (VERO) on
      gelatin coated microcarriers, using different concentrations (5, 10 and 15 g
      Cytodex 3/liter) cell densities up to 10(7) cells per ml were obtained. The
      described system is scaleable.

PMID- 1366653
TI  - Clonal derivatives of a human B-lymphoblastoid cell line producing prolactin--a
      cytogenetic characterization.
AB  - The IM-9-P cell line is a variant of the human B-lymphoblastoid cell line IM-9
      which ectopically secretes prolactin (hPRL). The heterogeneous line IM-9-P and
      three sublines of clonal origin, two of them positive and one negative for PRL
      gene expression, were subjected to cytogenetic analysis and compared with the
      reference line IM-9 which showed a normal female diploid karyotype. G-banding
      revealed several rearrangements in the chromosomes. Nine altered chromosomes
      including one stable marker chromosome were common to all analysed karyotypes of
      IM-9-P cells and their clones. A second marker chromosome 'mar2' occurred only in
      the karyotypes of the hPRL producing clones, but not in the non-producing clone.
      None of the visible alterations involve chromosome 6 which carries the PRL gene
      in humans.

PMID- 1366654
TI  - Establishment and characterization of a new human colon adenocarcinoma cell line:
      BCS-TC2.
AB  - A new cell line designated as BCS-TC2 was established in culture from a primary
      human colon adenocarcinoma. This cell line has been in continuous culture over a
      36-month period. The cells grow as a monolayer sheet, displaying areas with a
      multilayered pattern as well as single cells and free-floating aggregates. The
      morphological, immunological, and ultrastructural features of these cells are in
      agreement with their epithelial origin. The characterization of this cell line
      indicated a 38 hr doubling time, and a colony forming efficiency of 2% in
      semisolid media and 22% in liquid culture, at low cell densities. These cells
      produce low amounts of carcinoembryonic antigen in culture (0.1 ng of CEA/10(6)
      cells). Sub-cutaneous injection into athymic mice shows that these cells have a
      non-tumorigenic capacity. Chromosomal analysis showed a karyotype 46 XX, -15,
      +der (15), inv (16) (p13::q13). BCS-TC2 cell line, which maintains in culture
      several characteristics of the original tumor, represents a useful model system
      for cell biology studies of primary and non-metastatic tumors.

PMID- 1366655
TI  - Serial cultivation of suspended BHK 21/13 cells in serum-reduced and serum-free
      medium supplemented with various membrane protective agents.
AB  - Suspended BHK 21/13 cells were cultivated in 6M medium supplemented with PVP,
      bovine serum, LAH, YE, choline chloride and inositol at several concentrations.
      The maximum working capacity of the bioreactors was 400 ml and the experiments
      were run for 40 days. The growth promoting effects of each substrate were
      determined by calculation of generation numbers (n) in each culture. Viability
      testing and morphological detection of the cells were realized by the trypan blue
      exclusion method. As a result, the membrane protective effect of PVP, as
      suggested by some authors, was confirmed and it was estimated that the positive
      effects of PVP on cell propagation in cultures were due to its protective
      activities.

PMID- 1366657
TI  - Units for animal cell biotechnology.

PMID- 1366659
TI  - High density culture of hybridoma cells using a perfusion culture vessel with an
      external centrifuge.
AB  - The influence of centrifugal force on the growth of cells was examined by
      exposing the cells of the mouse-human hybridoma X87 line to centrifugal force
      (100-500 G) for ten minutes twice a day and comparing the static culture with
      that of unexposed cells. In this experiment, both cell proliferation and specific
      antibody productivity were independent of the centrifugal effect, and gave the
      same results as in the case of no exposure to centrifugal force. High density
      cultivation of the mouse-human hybridoma X87 line was obtained by a perfusion
      system where the cells were separated from the culture medium by continuous
      centrifugation. In the serum-free culture, the maximum viable cell density
      exceeded 10(7) cells/ml, and monoclonal antibody was stably produced for 37 days.
      The results in this culture were equivalent to those obtained by intermittent
      centrifugal cell separation from the culture medium, and separation by
      gravitational settlement.

PMID- 1366656
TI  - Doxorubicin effects on contractile structures and molecules.

PMID- 1366658
TI  - Hybridoma growth limitations: the roles of energy metabolism and ammonia
      production.
AB  - Energy metabolism and the production of ammonia in hybridoma cell culture and its
      inhibitory effects on cell growth are reviewed. The interactive roles of glucose
      and glutamine metabolism affect the rate of production of ammonia, and these
      interactions are described. It is shown that growth inhibition usually occurs
      between 2-4 mM ammonia although some cell lines have been shown to adapt to much
      higher concentrations, particularly in continuous culture. In batch cultures cell
      growth appears to be particularly susceptible to increased ammonia concentrations
      during the early stages of growth; ammonia increased the rate of cell death in
      the late stage of batch growth. The specific productivity of monoclonal
      antibodies is much less sensitive to the released ammonia than is growth; lower
      volumetric productivities relate to the lower viable cell concentrations which
      are achieved at the high ammonia levels. Techniques to prevent ammonia
      accumulation or remove ammonia selectively have been relatively unsuccessful to
      date.

PMID- 1366660
TI  - A continuous multistage roller reactor for animal cell culture: 1. Patterns of
      growth, production and catabolism of a murine hybridoma.
AB  - A Tubular Liquid Film Reactor was designed as a model system to transfer a batch
      culture kinetic to a continuous cascade. Cell density, product formation and
      substrate consumption rates were followed during fermentation at two dilution
      rates. In spite of the high dilution rates effective in each segment by itself
      high cell densities of up to 10(7) cells/ml were achieved due to cell
      sedimentation. The model character of the reactor was taken to determine critical
      values of substrate concentrations that influence production rates and result in
      an adaptation of metabolism.

PMID- 1366661
TI  - The use of macroporous gelatin carriers for the cultivation of mammalian cells in
      fluidised bed reactors.
AB  - A fluidised bed system for the cultivation of mammalian cells on a new type of
      macroporous gelatin microcarrier is described. The volumetric cell densities
      achieved under controlled conditions for two 'standard cell lines' (VERO, CHO)
      were one order of magnitude higher compared to conventional techniques using
      spherical microcarriers. The system can be potentially used for both anchorage
      dependent and independent cells.

PMID- 1366664
TI  - Use of lactate dehydrogenase release to assess changes in culture viability.
AB  - This study reports the use of lactate dehydrogenase release to monitor changes in
      culture viability in flask culture and fixed bed, porosphere bioreactor systems.
      Lactate dehydrogenase release shows good agreement with increase in non-viable
      cell numbers and decline in glucose utilisation in flask cultures. Studies with
      the immobilised system show that lactate dehydrogenase release can detect loss of
      viability which is not always indicated by a decrease in glucose utilisation. The
      data show that culture viability in a repeated-feed-and-harvest system is
      influenced markedly by both a) the medium change regime itself and b) the use of
      an immobilised bioreactor compared to a flask system for the same medium change
      regime.

PMID- 1366663
TI  - Industrial production of monoclonal antibodies and therapeutic proteins by
      dialysis fermentation.
AB  - A novel and powerful fermentation method is reported for the large-scale growth
      of mammalian cells and their secreted products. The system described illustrates
      many of the advantages of conventional batch fermentation processes but in
      addition has been shown to yield cell densities in excess of 1 x 10(7) cells/ml
      with concomitant increase in product concentration.

PMID- 1366665
TI  - Plant biotechnology goes commercial in Japan.

PMID- 1366666
TI  - Interspecific gene transfer: where next?

PMID- 1366667
TI  - Immobilization of animal cells in porous carrier culture.

PMID- 1366668
TI  - Transgenic fish.
AB  - A range of transgenic animal species have been generated using DNA
      microinjection, and application of this technique to fish is now showing some
      degree of success. Studies to optimize microinjection techniques specifically for
      use with fish, and to investigate possible alternative methods for mass culture,
      should lead to the commercial production of transgenic fish able to transmit
      desirable characteristics, such as enhanced growth or disease resistance, to
      their progeny.

PMID- 1366669
TI  - Enhanced transport and liquid membranes in bioseparations.
AB  - Membranes that use a reversible chemical reaction or sequestration to achieve
      high selectivities and productivities show great potential for use in
      bioseparations. The concept of liquid membranes, with and without a complexing
      agent (carrier), and the types of system configurations and carriers that may be
      used with these membranes, are discussed.

PMID- 1366662
TI  - Monoclonal antibodies to epidermal growth factor receptors in studies of receptor
      structure and function.

PMID- 1366670
TI  - Agitation effects on microbial cell-cell interactions.

PMID- 1366672
TI  - The rapid detection of direct-acting DNA mutagens by electrical impedence with a
      DNA repair-deficient strain of Escherichia coli.
AB  - A differential killing assay using Escherichia coli WP2 (wild type) and WP67
      (uvrA, polA) was combined with impedence microbiology to produce a rapid
      screening method for direct-acting mutagenic compounds. The assay showed that
      mitomycin C, N-nitroso guanidine, potassium dichromate, sodium azide and acridine
      orange were direct-acting mutagens. With this method results can be obtained
      within hours, as compared with two days for the standard Salmonella/microsome
      test.

PMID- 1366671
TI  - Deoxyribonuclease activity in rumen bacteria.
AB  - Deoxyribonuclease activity was surveyed in 22 strains belonging to 12 species of
      rumen bacteria, with lambda bacteriophage DNA as substrate. Activity was readily
      detected in broken cell preparations from 15 of these strains. Particularly high
      levels of activity were present in cells and culture supernatant of all 5 strains
      of Bacteroides succinogenes, and 2 out of 6 strains of Bacteroides ruminicola,
      examined.

PMID- 1366673
TI  - Calorimetric biosensors.

PMID- 1366674
TI  - Biosensors based on cell and tissue material.

PMID- 1366675
TI  - Fiber-optic biosensors.

PMID- 1366676
TI  - Amperometric biosensors.

PMID- 1366677
TI  - FET biosensors.

PMID- 1366678
TI  - Microbiosensors.

PMID- 1366679
TI  - Electrotransformation of intact cells of Brevibacterium flavum MJ-233.
AB  - Electroporation allowed transformation of intact cells of Brevibacterium flavum
      MJ-233. The two plasmids used for electroporation were pCRY2 (6.3 kilobase) and
      pCRY3 (8.2 kilobases). Both plasmids contain the chloramphenicol-resistance gene
      and the autonomous replication origin in B. flavum MJ-233. The efficiency of
      electrotransformation was optimal with cells harvested at the middle log phase of
      growth, and was improved by the addition of 1.0 U/ml of penicillin G to the
      culture medium. The optimum yield of transformants per micrograms DNA was 5 x
      10(4) when the cell suspension was pulsed at a cell density of 1 x 10(10)/ml and
      at a DNA amount of 1.0 micrograms.

PMID- 1366680
TI  - Bacterial conjugation between Escherichia coli and Pseudomonas spp. donor and
      recipient cells in soil.
AB  - Experiments conducted in microcosms containing loam soil samples inoculated with
      either E. coli or Pseudomonas spp. donor and recipient cells showed that
      bacterial cells survived and conjugated over a 24-h incubation period. E. coli
      transconjugants were detected 6 h after donor and recipient strains were
      introduced into sterile soil samples. In non-sterile soil samples,
      transconjugants were detected between 8 and 24 h incubation. Pseudomonas
      transconjugants were recovered from sterile soil samples between 6 and 12 h after
      their introduction and as early as 2 h in non-sterile soil. The results show that
      genetic interactions occur in non-sterile soil in relatively short periods of
      time at relatively high transfer frequencies (10(-3) to 10(-4]. Studies on
      genetic interactions in soil are becoming necessary in risk
      assessment/environmental impact studies prior to the release of genetically
      engineered or modified organisms into uncontained environments.

PMID- 1366681
TI  - Properties of the biosurfactant produced by Bacillus licheniformis strain JF-2.
AB  - The activity of the biosurfactant produced by Bacillus licheniformis strain JF-2
      was quantified using a unit defined as the amount of the acid-precipitated
      biosurfactant that lowered the surface tension by 10 mN/m. One unit was
      equivalent to 37 micrograms/ml of the acid-precipitated biosurfactant. Acid
      precipitation was very effective in the removal of the biosurfactant from the
      spent medium. Among the solvents tested methanol was the most efficient in
      extracting the surfactant activity from acid-precipitated material. Thin-layer
      chromatography of the acid-precipitated biosurfactant revealed four components,
      two of which contained a lipid moiety and one of which contained an amino group.
      The methanol-soluble fraction also contained these four components. Studies
      suggested that all four components were needed for full activity. The lowest
      interfacial tensions against octane were observed when NaC1 concentrations were
      50 g/l or greater. Calcium concentrations greater than 25 g/l significantly
      increased the interfacial tension.

PMID- 1366682
TI  - Potential and problems of animal cells in suspension culture.

PMID- 1366683
TI  - Growth behavior of Chinese hamster ovary cells in a compact loop bioreactor: 1.
      Effects of physical and chemical environments.
AB  - Chinese hamster ovary (CHO) cells were cultivated in a compact loop bioreactor
      using MEM-alpha medium supplemented with 10% fetal calf serum. Effects of
      physical and chemical environments, i.e., pH in the medium, stirring speed of
      impellers, temperature and partial pressure of oxygen (pO2) upon growth of
      suspended cells in the bioreactor were determined in batch cultures. Growth
      behavior was characterized by specific rates of growth (mu), glucose consumption
      (qG) and lactate production (qL), and the yield coefficients (cell yield from
      glucose, YX/G, and lactate yield from glucose, YL/G). An effect of medium
      osmolality was also evaluated with T-flask monolayer cultivation. The best growth
      was observed at pH 7.6, 37 degrees C, 400 rpm, 50-100% saturation with oxygen and
      320 mOsmol kg-1. Corresponding to the previous work with a human melanoma cell
      line, the sophisticated cultivation and process control systems have been
      improved for CHO cells.

PMID- 1366684
TI  - Growth behavior of Chinese hamster ovary cells in a compact loop bioreactor. 2.
      Effects of medium components and waste products.
AB  - Effects of biochemical factors, i.e., medium components and metabolic byproducts,
      on growth of Chinese hamster ovary (CHO) cells were investigated. Glucose and
      ammonia were found to inhibit the growth. Kinetic analysis gave the inhibition
      constants, 0.14 g l-1 for ammonia and 5.0 g l-1 for glucose. Since glutamine was
      unstable and was a main source of ammonia, precise studies on glutamine
      degradation and ammonia formation process were done. By evaluating the
      spontaneous reactions, net glutamine utilization and net ammonia production by
      the cells could be estimated. It became evident that asparagine could support the
      growth of CHO cells as a stable substitute for glutamine. Then, a glucose fed
      batch culture was grown on a glutamine free and asparagine supplemented medium.
      Because of (1) low glucose concentration, but (2) no glucose limitation and (3)
      low ammonia accumulation, the maximum total cell concentration reached 3.4 x
      10(6) ml-1, which was 1.8 times greater than that in the control experiment
      (initial 1.15 g l-1 glucose and 0.29 g l-1 glutamine, and no glucose feed).

PMID- 1366685
TI  - Studies on monoclonal antibody production by a hybridoma cell line (C1E3)
      immobilised in a fixed bed, porosphere culture system.
AB  - The aim of this study was to investigate the potential of fixed beds of
      macroporous glass spheres as a production process for animal cell products. The
      growth, metabolism and monoclonal antibody expression of a mouse-mouse hybridoma
      cell line was investigated in order to both test the potential of and to optimise
      the system. After the initial growth phase, the culture went into a steady-state
      phase brought on by glutamine limitation. An event occurred after 120-160 h of
      steady-state operation which destabilised the culture, causing a decline in
      productivity, after which the culture recovered. This event was analysed in
      detail to determine its cause, and whether a major switch in metabolic function
      had occurred. The parameter which correlated most closely to antibody production
      rate was oxygen, but as this was kept constant in the void medium of the bed it
      has to be concluded that oxygen diffusion into the spheres was the regulatory
      factor. A comparison of the fixed bed and a flask culture identified interesting
      differences in glucose metabolism between the two systems. The data gave strong
      indications as to how the productivity of the fixed bed system can be further
      improved. This includes optimisation of the glutamine concentration and modifying
      the porous structure of the spheres to improve diffusion characteristics.

PMID- 1366686
TI  - Serum-free media for lymphoid culture.
AB  - A serum-free medium is described that we have been using since almost ten years
      when growing a number of lymphoid cell lines. Serum-free media offer several
      advantages before media containing even well standardized animal sera. As an
      example of studies where serum-free media offer advantages we present data
      demonstrating the use of a defined medium when monitoring glycosidase enzyme
      levels in lymphoid cells.

PMID- 1366687
TI  - Regulatory mechanisms of eicosanoids biosynthesis in processes related to human
      reproduction: comparison between studies with tissue and primary cell cultures.

PMID- 1366688
TI  - The protective effect of serum against hydrodynamic damage of hybridoma cells in
      agitated and surface-aerated bioreactors.
AB  - The effect of serum on the growth rate and metabolism of CRL-8018 hybridoma cells
      in an agitated, surface-aerated bioreactor was examined. In the employed well
      controlled bioreactors at high agitation rates, hybridoma cells in medium
      containing 1% fetal bovine serum rapidly die in the presence of a vortex with
      accompanying gas-bubble entrainment, whereas non-agitated control cultures grow
      normally in medium containing 1% serum. Serum levels greater than 5% counteract
      the detrimental hydrodynamic effects due to agitation and bubble entrainment. The
      protective effect is present after short-term (less than 1 h) exposure to 10%
      serum concentration, suggesting a protection mechanism which is, at least in
      part, of a physical nature. The apparent cell yields on glucose, lactate, and
      glutamine decreased with decreasing growth rate due to low serum concentrations.
      The results are incorporated into a simple model in which the apparent growth
      rate is the sum of an invariable growth rate and a changing death rate.

PMID- 1366689
TI  - Methods for increasing monoclonal antibody production in suspension and entrapped
      cell cultures: biochemical and flow cytometric analysis as a function of medium
      serum content.
AB  - The growth and antibody production of the SP2/0-derived hybridoma HB124 (ATCC)
      grown in media containing varying amounts of fetal bovine serum (FBS) were
      monitored using biochemical and flow cytometric methods. Hybridomas grown in 100
      ml spinner flasks with RPMI-1640 containing varying amounts of serum demonstrated
      that cell growth, viability and IgG production show significant changes when
      serum content is decreased from 10.0 to 5.5 to 1.0 and 0.5%. A longer lag phase
      resulted when the lower serum content media were used. Cellular rates of glucose
      uptake showed a significant increase as serum levels were lowered. Similarly,
      exponential phase IgG production rates increased as the amount of serum was
      decreased, probably as a result of the decreased rate of exponential growth. Flow
      cytometric analysis showed a similar increase in cellular IgG content as medium
      serum levels declined. In contrast, the maximum IgG concentrations were found in
      flasks containing 1% FBS or above with the lowest concentration in the 0.5% FBS
      flask being due to the lower numbers of viable cells. Cells grown in microporous
      hollow fiber reactors were fed with medium containing serum which was decreased
      stepwise with time. Decreasing medium serum content stepwise from 10 to 2.5%
      resulted in increased antibody production. However, complete removal of serum
      from the medium resulted in a significant drop in antibody productivity.
      Cumulative antibody production was equivalent for cells grown entirely in medium
      containing 10% FBS and for those which experienced a drop to 2.5% FBS. To compare
      a defined serum-free medium preparation with medium containing 10% FBS, cells
      were again grown in batch suspension culture and analyzed. The growth rates were
      similar but there was a significant difference in IgG production rates. The serum
      free culture exhibited both higher cellular production rates and higher IgG
      concentrations. These results indicate that decreasing medium serum content can
      adversely affect antibody yield because of lower cell viabilities, not because of
      lower production rates. Use of a defined serum-free medium, as done in this
      study, results in higher yields because of a higher IgG production rate as well
      as good cell growth and viability.

PMID- 1366690
TI  - The effect of pH on the toxicity of ammonia to a murine hybridoma.
AB  - The growth inhibition of a murine hybridoma mediated by ammonium chloride was
      shown to vary with the pH of the culture medium. Values for the initial media
      concentration causing 50% growth inhibition (IC50) ranged from 4 mM to 7.6 mM as
      the pH was reduced from 7.8 to 6.8. A significant negative correlation was
      observed between the IC50 and the NH3 concentration of the medium, suggesting
      that ammonia and not ammonium may be the toxic species in the culture medium. The
      optimum initial pH for cell growth was 7.4. However, this optimum shifts to lower
      pH as ammonia accumulates in culture as a metabolic by-product. This suggests
      that in order to obtain high cell yields, it may be beneficial to adopt a culture
      strategy of lowering pH during cell growth to offset the inhibitory effects of
      accumulated ammonia.

PMID- 1366691
TI  - Monoclonal antibodies to bis-indole alkaloids of Catharanthus roseus and their
      use in enzyme-linked immuno-sorbent-assays.
AB  - High affinity monoclonal antibodies directed against bis-indole alkaloids from
      Catharanthus roseus were produced. Once characterized, they were used to develop
      sensitive enzyme-linked-immuno-sorbent-assays, enabling us to determine minute
      quantities of alkaloids related to vinblastine in plant material.

PMID- 1366693
TI  - Characterization of maize polyamine oxidase.
AB  - Some structural and biochemical characteristics of polyamine oxidase (PAO)
      purified from maize shoots have been examined. The enzyme has only alanine as N
      terminal amino acid and its N-terminal sequence shows a significant degree of
      homology with tryptophan 2-monooxygenase from Pseudomonas syringae pv.
      savastanoi. The pH optimum for the stability of the native enzyme is 5, similar
      to that of the barley leaf enzyme. Calorimetric analysis shows a single two-state
      transition at pH 6 with Tm 49.8 degrees. At pH 5 the thermal stability is
      increased by more than 14 degrees. Amine oxidation products, delta 1-pyrroline
      and diazabicyclononane, are competitive inhibitors of PAO activity (apparent Ki =
      400 and 100 microM respectively). Moreover these compounds improve the thermal
      stability of the enzyme. N1-Acetylspermine, which is a good substrate for
      mammalian PAO, acts as a non-competitive inhibitor for the plant enzyme.

PMID- 1366692
TI  - Biotransformation of 18 beta-glycyrrhetinic acid by cell suspension cultures of
      Glycyrrhiza glabra.
AB  - Two biotransformation products formed from 18 beta-glycyrrhetinic acid by cell
      suspension cultures of Glycyrrhiza glabra were isolated and their structures
      determined by chemical and spectral data as 3-O-[alhpa-L-arabinopyranosyl-(1---
      2)-beta-D-Glucuronopy ranosyl]-24- hydroxy-18 beta-glycyrrhetinic acid and 30-O
      beta-D-glycopyrano-syl-18 beta-glycyrrhetinic acid. The formation of
      glycyrrhizin, the main triterpene glucuronide of the licorice root, was not
      detected among the biotransformation products. This is the first report of the
      glucuronylation of an exogenous triterpene in plant cell cultures.

PMID- 1366694
TI  - Multiple forms of endopeptidase activity from jojoba seeds.
AB  - The cotyledons of 27 day post-germination jojoba seedlings (Simmondsia chinensis)
      contained five distinct endopeptidase activities separable by DEAE Bio-Gel and CM
      cellulose ion exchange chromatography. The endopeptidases were purified 108- to
      266-fold and their individuality was confirmed by activity-specific assays in
      native acrylamide gels along with differences in their Mr and catalytic
      properties. The five endopeptidases, which showed activity on model substrates
      and protein, were named EP Ia, EP Ib, EP II, EP III and EP IV. EP Ia was a serine
      proteinase with a pH optimum of ca 8 and Mr of 58,000. EP Ib, II and III were
      discrete cysteine proteinases showing pH optima of ca 6.8, 6.0 and 5.4 and Mr of
      41,000, 47,000 and 35,000 respectively. EP IV was an aspartic acid proteinase
      with a ca pH optimum of 3.5 and Mr of 33,000.

PMID- 1366695
TI  - ent-labdane glycosides from Baccharis pingraea.
AB  - The aerial parts of Baccharis pingraea, collected in Chile, afforded, in addition
      to two diterpene glycosides isolated previously, 14 new ones and two of the
      corresponding desacyl aglycones. The structures were elucidated by high field 1H
      NMR spectroscopy. The differences between the collections from Argentina and
      Chile are discussed.

PMID- 1366696
TI  - Kaempferol 3-rhamnoside-7-[6-feruloylglucosyl (1----3)rhamnoside] from Asplenium
      prolongatum.

PMID- 1366697
TI  - Interfacial mass transfer in extraction of amino acid by ALIQUAT 336 in organic
      phase.
AB  - Reactive extraction of L-phenylalanine from alkaline aqueous solution into xylene
      in the presence of tri-octyl-methyl-ammonium chloride (ALIQUAT 336) as complexing
      agent was studied using a stirred transfer cell. The study investigated the
      effects of carrier concentration and temperature on mass transfer rates. Transfer
      rate across the interface in the presence of surfactant molecules was also
      studied. A two-film model was proposed by considering film mass transfer
      resistances at the aqueous and organic phases. The model predicted adequately the
      experimental time-concentration data at different carrier concentrations and
      temperatures. The model was modified to take into account the presence of
      surfactant in the organic phase.

PMID- 1366698
TI  - Electrically enhanced extraction of penicillin G into dichloromethane.
AB  - The application of electrically enhanced liquid-liquid extraction techniques to
      the recovery and purification of penicillin G from aqueous solutions and from
      untreated mycelial culture broth is described. Experiments at laboratory scale
      have shown that extraction rates into dichloromethane at pH 4.0 may be increased
      by factors of up to five-fold by electrostatically spraying penicillin G
      solutions into a continuum of solvent held in electrical tension. The
      experimental studies revealed that in small spray column contactors,
      electrostatic spray conditions, once initiated at nozzle voltages in excess of 10
      kV, could be sustained at nozzle voltages as little as 4 kV. The results
      demonstrate the potential of this technique as an alternative to mechanically
      augmented liquid-liquid contact for the intensification of whole broth extraction
      processes.

PMID- 1366699
TI  - Transient response of a solid-liquid model biological fluidised bed to a step
      change in fluid superficial velocity.
AB  - The evolution of a solid-liquid model biological fluidised bed under a step
      change in fluid superficial velocity is described. During a transient step
      change, the fluidised bed divides into a top zone which remains at the initial
      porosity and a bottom zone which settles at the final porosity. The interface of
      discontinuity in porosity moves progressively upwards through the fluidised bed.
      The velocity at which the top of the fluidised bed expands or contracts and the
      upward velocity of the porosity transition interface depend only upon the initial
      and final states of the bed porosity and the fluid superficial velocity. This
      results in a linear evolution with time of the total bed height and the height of
      porosity transition interface. The proposed model is well suited to describe the
      transient response of low-density particles in a fluidised bed, such as
      encountered in biological systems, to a sudden change of liquid superficial
      velocity. The model was validated experimentally.

PMID- 1366700
TI  - Thermodynamics and kinetics of lipase catalysed hydrolysis of oleyl oleate.
AB  - The kinetics of enzymatic hydrolysis of oleyl oleate in the boundary layer
      between stagnant organic and aqueous phases was studied using a commercial lipase
      preparation which was dissolved in the aqueous phase. Three aspects of the
      reaction were investigated. (1) The hydrolysis equilibrium in the organic phase
      cannot be expressed in terms of the concentrations of ester, alcohol and organic
      acid alone since the activity of the organic compounds changes dramatically with
      conversion, i.e. with the water content in the organic phase. An empirical
      correlation that accounts for the water activity and the unknown activity
      coefficients of the organic compounds is determined. (2) The influence of the
      interfacial area was examined, and it was found that the amount of ester
      converted per unit area of interface is independent of the available interfacial
      area and of the amount of ester. (3) The inhibition of the reaction by the
      hydrolysis products and by n-alkanes was measured. Both acid and alcohol inhibit
      the hydrolysis reaction while the influence of long-chained alkanes is very
      small. It is concluded that the reaction rate is determined by the interfacial
      concentrations, and that these concentrations differ from the bulk concentrations
      because of the different surface affinities of the components.

PMID- 1366701
TI  - Folding of eukaryotic proteins produced in Escherichia coli.
AB  - Although intracellular expression in E. coli may result in accumulation of the
      eukaryotic protein in inclusion bodies, the protein may often be recovered by
      first solubilizing with denaturant followed by refolding. Some general guidelines
      for developing a refolding procedure are apparent but the specific protocol must
      be empirically determined for each protein. Convenient and rapid assays for
      detecting native protein are critical for developing a refolding procedure.
      Maintaining solubility during refolding is a common feature of recovery
      processes. Proper folding should be assessed by a number of methods including
      activity, spectroscopic and stability measurements. For some proteins, properly
      folded protein may be obtained by secretion from E. coli; however, secretion does
      not ensure correct folding and protection from proteolytic degradation.

PMID- 1366702
TI  - Human retinoblastoma susceptibility gene.
AB  - It is clear that the RB-deficient tumor cells lost their tumorigenicity in nude
      mice after regaining the RB gene expression. However, the mechanism of tumor
      suppression by the RB gene is still unknown. More studies on the biological
      activities of RB protein, pp110RB, are necessary to answer this question. Recent
      studies have shown that several oncogenic viral proteins, such as SV40 large T
      antigen (47) and adenoviral E1A protein (48), bind to RB protein. The
      significance of these bindings remains unclear; nevertheless, they suggest that
      depletion of functional RB protein by viral proteins may provide another
      mechanism of RB inactivation. Continued study of naturally occurring as well as
      engineered RB mutants may give us some information on the biological activity of
      RB protein, and its roles in oncogenesis, differentiation, development and gene
      regulation. Additionally, direct detection of RB gene mutations would have great
      clinical utility. Probes for the RB gene and gene product will be useful for
      genetic diagnosis of cancer susceptibility in affected families. Therefore,
      antibodies to the RB protein will be excellent tools for diagnostic and/or
      prognostic application in clinical medicine.

PMID- 1366703
TI  - The genes encoding wheat storage proteins: towards a molecular understanding of
      bread-making quality and its genetic manipulation.

PMID- 1366705
TI  - Electroporation of bacteria: a general approach to genetic transformation.

PMID- 1366704
TI  - Control of translation initiation in mammalian cells.

PMID- 1366706
TI  - The isolation and identification of cDNA genes by their heterologous expression
      and function.
AB  - Functional cDNA genes for cell surface proteins, receptors, growth factors and
      nuclear and cytoplasmic proteins can be isolated by a heterologous expression
      function gene isolation strategy. The method of this strategy is dependent on
      highly efficient mammalian expression vectors, the properties of COS cells as
      hosts for SV40-origin-containing mammalian expression vectors, the well
      established technology of constructing highly complex plasmid cDNA libraries and
      on the sensitivity of biological assays. These technologies are combined to
      identify a specific gene sequence by its biological phenotype. In theory this can
      be accomplished by individually testing each single gene of the cDNA library by
      expression in COS cells. In practice complex cDNA libraries are formed so that
      multiple cDNA genes can be tested and analyzed simultaneously. When the
      biological assay can discriminate phenotypic changes at the single cell level as
      typified by cellular morphology, cell membrane proteins or receptors or
      intracellular enzymes, then a reiterative expression screening method can be
      used. This was demonstrated by the isolation of cDNA genes encoding cell membrane
      proteins (7-10, 12). For the isolation of cDNA genes for growth factors and
      cytoplasmic enzymes by the expression-function cDNA gene isolation strategy, an
      alternative method is followed. The cDNA library is partitioned into sets of cDNA
      clones for transfection and analysis. The number of clones in a set is dependent
      on the efficiency of the expression vector used and on the sensitivity of the
      biological assay. For secreted cytokines and growth factors which can be simply
      detected by factor dependent cell lines, about 1,000 cDNA clones can be tested as
      a single set. By this strategy the genes for numerous hematopoietic growth
      factors, cytokines and interleukins have been isolated. With such numerous
      successes we can expect that the heterologous expression-function cDNA gene
      isolation strategy will become an important molecular biology method.

PMID- 1366707
TI  - Molecular cloning of genes encoding transcription factors with the use of
      recognition site probes.

PMID- 1366708
TI  - From footprint to function: an approach to study gene expression and regulatory
      factors in transgenic plants.

PMID- 1366709
TI  - Purification of recombinant proteins with metal chelate adsorbent.

PMID- 1366710
TI  - Determinants of translation efficiency of specific mRNAs in mammalian cells.

PMID- 1366711
TI  - High performance isoelectric focusing using capillary electrophoresis
      instrumentation.
AB  - High performance isoelectric focusing in capillaries provides rapid, high
      resolution separation of proteins based on their isoelectric points. Results can
      be obtained in a matter of minutes with little or no sample preparation. The
      technique requires the use of coated capillaries to reduce electroendosmosis so
      that stable, focused zones can be attained. Once focused, protein zones may be
      mobilized by the addition of salt to the catholyte or anolyte buffer. On-tube UV
      monitoring enables direct detection of sample components during mobilization with
      mass sensitivity equal to that of silver staining. The linear relationship
      between mobilization time and isoelectric point allows the technique to be used
      for estimation of protein pI. Demonstrated applications include separation of
      proteins in biological fluids with possible clinical applications, and
      characterization of biopharmaceutical proteins and monoclonal antibodies.

PMID- 1366712
TI  - Versatile serum-free media formulations.

PMID- 1366713
TI  - Analysis and isolation of natural products using a rotation planar chromatograph.

PMID- 1366714
TI  - Peptide technology.

PMID- 1366715
TI  - Cost effective environmental control: putting biotechnology to work.

PMID- 1366716
TI  - The uptake of heavy metal ions by algae.

PMID- 1366718
TI  - Should animal cell biotechnology be self sufficient?

PMID- 1366717
TI  - The application of fungal protoplasts in biotechnology.
AB  - Fungi are organisms of enormous industrial importance, and are used for the
      production of compounds such as antibiotics, organic acids and
      immunosuppressants. Many studies have suggested that their industrial value may
      in some cases be increased by exploitation of technologies involving fungal
      protoplasts, where the cell wall has been removed, usually enzymically. This
      article critically examines what the advantages of using protoplasts are, the
      current methodology for the preparation, and how they behave subsequently.

PMID- 1366719
TI  - Electron microscopy of hybridoma cells with special regard to monoclonal antibody
      production.
AB  - Electron microscopy of mouse hybridoma cell lines shows that the major difference
      between non, low and high producer cell lines is the amount of endoplasmic
      reticulum. Vesicular-tubular or cavernous structures of endoplasmic reticulum,
      which can survive long after cell death, are particularly abundant in producer
      cell lines. Immunogold labelling with anti-mouse IgG reveals that antibodies are
      predominantly located in these structures. The cell membrane undergoes structural
      changes during the late stages of batch culture with the disappearance of
      microvilli and the appearance of blebs and deep indentations. Necrosis disrupts
      the cytoplasmic structures and the nucleus is last to degrade.

PMID- 1366720
TI  - Improvement in the antibody productivity of human-human hybridomas by
      transfection with Tac gene.
AB  - The presence of a highly purified recombinant interleukin-2 (rIL-2) increased the
      production of immunoglobulin (IgM or IgG) by human-human hybridomas to 1.5-2.0
      times the production by untreated cells. However, these cells did not react with
      anti-Tac (IL-2 receptor alpha) antibody. To enhance the response of the hybridoma
      cells to rIL-2, Tac gene was introduced by co-transfection with Tac gene
      expression plasmid pTB459 and G418 resistant gene expression plasmid pRSVneo. Tac
      cDNA transfected hybridoma (HBW-4.16.459-6-126) was induced to produce 6 times as
      much IgG by rIL-2 as was the control. This antibody production promoting
      phenomenon mediated by rIL-2 was depressed by anti-Tac antibody.

PMID- 1366721
TI  - Viral contamination of monoclonal antibody preparations: potential problems and
      possible solutions.

PMID- 1366722
TI  - Methods for determination of growth-rate-dependent changes in hybridoma volume,
      shape and surface structure during continuous recycle.
AB  - Hybridoma volume and surface membrane structure were found to vary as a function
      of specific growth rate using a method of cell recycle with continuous medium
      perfusion to vary growth rate. Mean hybridoma volume determined at constant
      osmolality by both electronic particle counting and scanning electron microscopic
      (SEM) methods indicated that rapidly growing cells are significantly larger than
      very slowly growing cells. We have previously determined that during both rapid
      and slow growth over a range of L-glutamine provision rates (Gln PR) that
      specific monoclonal antibody (MoAb) secretion rate was not changed. In this study
      a constant MoAb secretion rate per unit of membrane area was found which may
      indicate that changing membrane area is not a rate-determining factor in MoAb
      secretion. SEM methods were of limited use for accurate determination of cell
      volume due to cell shrinkage and large coefficients of variations. In spite of
      this limitation, SEM stereology methods were useful in confirming that cells
      remained spherical over a wide range of specific growth rates and that hybridoma
      cells were not circular. Sequential SEM observations also revealed that surface
      membrane structure of the 9.2.27 murine hybridoma investigated was correlated
      with growth rate. Under conditions of very slow growth, hybridoma surface
      microvilli density appeared to be significantly reduced.

PMID- 1366723
TI  - A comparison of different culture methods for hybridoma propagation and
      monoclonal antibody production.
AB  - A major variable to consider in the production of biologicals from mammalian cell
      cultures is the mode of operation, be it a batch, continuous, perfusion, fed
      batch or other production method. The final choice must consider a number of
      fundamental and economic issues. Here we present some antibody production data
      from different cell lines using different modes of production and discuss the
      important factors for consideration in choosing a production strategy. It was
      found that the productivity of batch cultures was lower than that obtained in
      continuous and perfused cultures, but that productivity could be improved by
      implementing suitable feeding strategies. The antibody productivity of one cell
      line, MCL1, during exponential phase was not affected by media type or glucose
      level. The maximum productivity of two cell lines in continuous culture was found
      to occur at dilution rates below the maximum, from 0.019 to 0.030 hr-1.

PMID- 1366724
TI  - Batch production and secretion kinetics of hybridomas: pulse-chase experiments.
AB  - Pulse chase experiments of two mouse hybridoma lines were conducted in order to
      elucidate the kinetics of monoclonal antibody (mAb) production and secretion
      during different stages of batch cultures. The results indicate that a stock of
      cytoplasmic IgG exists in hybridoma cells and that the concentration of this
      stored IgG depends on the cell line used and the stage of the culture. This
      stored IgG can be released by dying cells, and a certain quantity of the secreted
      IgG is derived from this source. However, only between 0.3 and 9.3% of the
      released IgG of U0208 (average: 2.08%) and between 2.08 and 25.8% of the IgG,
      released from I.13.17 (average: 6.95%), were of storage origin, calculated on
      culture viability and intracellular IgG-stock. Comparing the accumulation of
      radio-labelled IgG (IgG*) in the supernatant with the reduction of cytoplasmic
      IgG* during the chase experiments, the percentages range between 14 and 50%,
      somewhat higher values probably caused by changes in the culture conditions.
      These changes led to a release of IgG during the chase experiments, which
      accounts for about 20-25% of the totally secreted IgG. It could be established
      that during the logarithmic growth phase of batch cultures a certain percentage
      of synthesized IgG was not released but stored within the cells: for U0208: 0.3
      4.5%, for I.13.17: 1-7.6%. During the stationary and death phase, this percentage
      ranged between 1.5 and 20% for U0208 and between 0.5 and 8.1% for I.13.17.
      Finally, the chase experiments also revealed that the time of synthesis,
      assembly, and secretion of mAbs does not vary much during the different phases of
      batch cultures, and is within the range of 1.5 and 3 hrs.

PMID- 1366725
TI  - Continuous gene expression in vitro: the Spirin system.

PMID- 1366726
TI  - Detection of bacteria by transduction of ice nucleation genes.

PMID- 1366727
TI  - More about complementary hydropathy.

PMID- 1366728
TI  - New tools for protein sequence analysis.
AB  - Analysis of protein sequence is an important tool in studies of both native and
      recombinant proteins. Novel techniques and instrumentation which facilitate
      determination of protein primary structure have recently been developed.

PMID- 1366729
TI  - Cryopreservation and the maintenance of cell lines.
AB  - Techniques for cell-line preservation which enable reliable and reproducible
      recovery of material with unchanged, defined characteristics are essential in
      many biotechnology industries. Cryopreservation is one such technique, and in
      this review we explore some of its problems, successes and potential future
      applications.

PMID- 1366731
TI  - Yeast: the model 'eurokaryote'?

PMID- 1366730
TI  - Antigen delivery systems for analysing host immune responses and for vaccine
      development.
AB  - Overall, the meeting was timely and worthwhile. It is evident that there is a
      need for comparative studies to establish a firm foundation for future work. This
      is particularly important since it appears that the responses observed are
      influenced by the particular strain used for attenuation, the means of
      attenuation, the antigen-presentation system employed and the animal most
      immunized. In this last regard, one must recognize that most work to date has
      been with inbred strains of mice which differ from the genetic diversity of most
      hosts that are the intended beneficiaries of the immunization strategies being
      developed.

PMID- 1366732
TI  - Engineering enzymes for non-aqueous solvents.
AB  - Enzymes may be redesigned to permit catalysis in non-aqueous solvents by
      engineering their amino acid sequences, thereby altering their physical and
      chemical properties to suit the new solvent environment. The interactions that
      contribute to protein stability in non-aqueous solvents are discussed in the
      context of attempting to identify possible approaches to constructing enzymes
      which exhibit enhanced stability in non-aqueous media. These approaches are
      illustrated by several examples where protein engineering has resulted in enzymes
      that are better suited for catalysis in organic solvents.

PMID- 1366733
TI  - Peptidomimetics and the template approach to nucleation of beta-sheets and alpha
      helices in peptides.
AB  - Introducing structural constraints into engineered analogs of natural proteins is
      important for defining essential characteristics, such as specificity or
      stability, of the protein. This may be achieved by the use of peptidomimetics-
      elements which mimic the structure of natural peptide components, or
      conformational templates which induce specific structure formation in contiguous
      peptide sequence.

PMID- 1366734
TI  - Antibody geometry and form: three-dimensional relationships between anti
      idiotypic antibodies and external antigens.
AB  - Anti-idiotypes have been developed to mimic a wide variety of antigens in studies
      of antibody-antigen interactions. Molecular, biochemical and structural analysis
      of antibody-anti-idiotype pairs presents an excellent model for study of complex
      protein-protein interactions. An understanding of the ways in which anti
      idiotypes mimic antigens and the features determining binding characteristics
      will facilitate rational design of compounds with biological, enzymatic,
      pharmaceutical and chemical applications.

PMID- 1366735
TI  - Site directed mutagenesis: a tool for enzyme mechanism dissection.
AB  - Protein engineering has become the principle means of examining the active site
      of an enzyme to identify and quantify the roles of specific residues in ligand
      binding, specificity and catalysis. Site-specific mutagenesis has extended our
      knowledge gained from X-ray crystallography, and has provided striking proof that
      the intricate active-site geometry is supported by the remainder of the protein
      infrastructure for maximum catalytic efficiency.

PMID- 1366737
TI  - Affinity chromatography: a technology update.

PMID- 1366736
TI  - An improved amperometric immunosensor for the detection and enumeration of
      protein A-bearing Staphylococcus aureus.
AB  - An amperometric immunosensor specific to the protein A of Staphylococcus aureus,
      was developed using the direct electrochemical detection of phenol produced by
      alkaline phosphatase from phenylphosphate. The immunosensor could detect protein
      A at 0.01 ng/ml and could reliably detect and quantify pure cultures of protein A
      bearing Staph. aureus above 10(3) cfu/ml. A similar sensitivity of detection was
      obtained with samples of beef and milk.

PMID- 1366738
TI  - Independent simultaneous multiple peptide synthesis.

PMID- 1366739
TI  - New interface mates HPLC with GC detectors: an answer to a chromatographer's
      prayer.

PMID- 1366740
TI  - Development of a highly specific diagnostic 23S rDNA oligonucleotide probe for
      Mycobacterium leprae.
AB  - A 21-mer DNA oligonucleotide probe targeting the 23S rRNA of Mycobacterium leprae
      was developed and its high specificity demonstrated by dot-blot hybridization.
      Even under relaxed hybridization and washing conditions (20 degrees C below Tm)
      the probe was highly selective in that positive signals were only detected with
      M. leprae, about half of the slow-growing and one of the fast-growing reference
      mycobacteria and Gordona bronchialis. At more stringent washing temperatures (6
      degrees C below Tm) only the rRNA of Mycobacterium leprae was detectable.

PMID- 1366741
TI  - Lipase production by free and immobilized protoplasts of Sporotrichum
      (Chrysosporium) thermophile Apinis.
AB  - Production of lipase by free and alginate-entrapped protoplasts was studied in
      batch culture. Cell-wall-degrading enzymes Novozym 234 and cellulase CP improved
      lipase secretion of normal mycelium by 25%-100%. The protoplast-regenerated
      mycelium exhibited several-fold higher lipase activity in batch replacements in
      TRIS buffer over normal spore-derived mycelium. The specific lipase activity of
      immobilized protoplasts was about four times higher than normal mycelial beads.
      Protoplasts beads were stable and retained high enzyme activity even after three
      buffer replacements lasting 120 h; TRIS buffer was better than acetate or normal
      glucose medium. A minimum of 8 h regeneration period was necessary for lipase
      synthesis. Triolein, olive oil, tributyrin and oleic acid butylester were able to
      induce lipase in immobilized protoplasts. Tween 80 enhanced lipase activity of
      the immobilized protoplasts. Partially degraded immobilized mycelium was nearly
      as effective as normal immobilized protoplasts for lipase secretion. Both free
      and immobilized protoplasts could be reused for up to 200 h with some loss in
      enzyme activity.

PMID- 1366742
TI  - Production of cholera toxin subunit B by a mutant strain of Vibrio cholerae.
AB  - The B subunit (CTB) of cholera toxin (CT) can be used as a carrier protein for
      conjugate vaccines designed to elicit antipolysaccharide antibodies. A defined
      medium, AGM4, was designed to grow a high-producing mutant of Vibrio cholerae
      expressing only the B subunit of CT: V. cholerae 0395-NI. AGM4 contains four
      amino acids, asparagine, glutamic acid, arginine and serine, salts and a trace
      element solution. The carbon source is glucose. The fermentations performed in
      AGM4 indicated that CTB production paralleled the growth of the organism but that
      there was a maximal release of CTB during the stationary phase. There was a clear
      optimum of productivity at pH 8.0 and 30 degrees C. The pH had an influence on
      CTB production and not only on its release. Analysis of the amino acids present
      in the medium showed a correlation between their consumption rates and CTB
      productivity.

PMID- 1366743
TI  - Differences in short peptide-substrate cleavage by two cell-envelope-located
      serine proteinases of Lactococcus lactis subsp. cremoris are related to secondary
      binding specificity.
AB  - Various chromophoric peptides have been tested as substates for two genetically
      related types (PI and PIII) of cell-envelope proteinases of Lactococcus lactis
      subsp. cremoris. The positively charged peptide methoxy-succinyl-arginyl-prolyl
      tyrosyl-p-nitroanilide appeared to be cleaved with the highest catalytic
      efficiency by both enzymes, although in the case of PIII only at high ionic
      strength. A cation binding site in the PI-type proteinase that is not present in
      the related PIII-type appears to be mainly responsible for the difference between
      these enzymes with respect to the rate of conversion of this chromophoric
      substrate at relatively low ionic strength. This cation binding site most
      probably resides in the aspartic acid residue 166, which in PIII is substituted
      by asparagine. Substitution of the threonine residue 138 by lysine in PIII may
      also play a role. The binding step in the reaction pathway catalysed by PI at low
      ionic strength is governed mainly by an ionic interaction involving the cation
      binding site. In addition, hydrophobic interactions contribute to the binding
      process. Masking of the cation binding site only increases the Michaelis constant
      Km; the catalytic constant kcat is not affected. In the absence of the cation
      binding site (viz. in PIII) the free energy derived from the hydrophobic
      interactions only is too small to promote binding of the substrate effectively.
      High activities are measured only if a high ionic strength is introduced. Removal
      of electrostatic repulsion between the substrate and positively charged residues
      of the enzyme, among which is lysine 138, may contribute to this
      activation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1366744
TI  - Enhancement and stabilization of the production of glucoamylase by immobilized
      cells of Aureobasidium pullulans in a fluidized-bed reactor.
AB  - Glucoamylase production by Aureobasidium pullulans A-124 was compared in free
      living cells, cells immobilized in calcium alginate gel beads aerated on a rotary
      shaker (agitation rate 150 rpm), and immobilized cells aerated in an air bubble
      column reactor. Fermentation conditions in the bioreactor were established for
      bead concentration, substrate (starch) concentration, calcium chloride addition
      to the fermentation medium, and rate of aeration. Production of glucoamylase was
      optimized at approximately 1.5 units of enzyme activity/ml medium in the
      bioreactor under the following conditions: aeration rate, 2.0 vol air per working
      volume of the bioreactor (280 ml) per minute; gel bead concentration, 30% of the
      working volume; substrate (starch) concentration, at 0.3% (w/v); addition of
      calcium chloride to the medium at a final concentration of 0.01 M. Productivity
      levels were stabilized through the equivalent of ten batches of medium with the
      original inoculum of immobilized beads.

PMID- 1366745
TI  - A constitutive expression vector system driven by the deo P1P2 promoters of
      Escherichia coli.
AB  - The P1P2 promoters of Escherichia coli K12 deo operon, residing on an AvaII
      restriction fragment, were used to construct a new expression vector. To evaluate
      the potential of the P1P2-driven expression system we have inserted the sequence
      of human superoxide dismutase (hSOD) downstream of the deo ribosome binding site.
      Expression of hSOD was evaluated by means of sodium dodecyl sulphate
      polyacrylamide gel electrophoresis and enzyme activity. In crude cell extracts
      hSOD expression levels were found to be high in hosts possessing no deoR or cytR
      repressors. Highest levels of hSOD expression were obtained with a high-copy
      number plasmid regardless of the host used. Expressed hSOD can account for 35%
      40% of total protein in E. coli.

PMID- 1366746
TI  - Pigmented variants of Tolypocladium inflatum in relation to cyclosporin A
      production.
AB  - We have isolated four distinct colony types of the fungus Tolypocladium inflatum,
      the producer of the immunosuppressive agent cyclosporin A: morphologically normal
      white, red, and orange colonies and morphologically diverse tiny brown colonies.
      In liquid cultures, white normal and brown colonies developed into yellow broths.
      The broth of the brown colony had a low final pH and low cyclosporin production,
      whereas orange and red colonies had dark brown and even black broths with higher
      final pH and high cyclosporin production. The specific production of cyclosporin
      A by the red colony was three times that of the white normal colonies.

PMID- 1366747
TI  - Storage and growth of neuroblastoma cells immobilized in calcium-alginate beads.
AB  - Mouse neuroblastoma cells (N18) were immobilized in calcium-alginate gel beads.
      Under standard culture conditions (37 degrees C; 5% CO2), cell growth was
      observed inside the beads. The number of cells increased threefold during 7 days
      of culture with cell division and differentiation visualized by electron
      microscopy. Cell properties maintained after short-term storage (2-3 days at 4
      degrees C) included: (i) properties of voltage-dependent ionic channels tested by
      patch-clamp electrophysiological techniques; (ii) expression of cell-adhesion
      membrane proteins tested by immunohistochemistry (iii) morphological
      differentiation obtained by depletion of foetal calf serum in culture medium. The
      advantages of such an immobilization technique as applied to neurone cells are
      discussed.

PMID- 1366748
TI  - Influence of the reaction medium on the product distribution of peroxidase
      catalysed oxidation of p-cresol.
AB  - p-Cresol was oxidized by hydrogen peroxide in a reaction catalysed by horseradish
      peroxidase and the low molecular weight products were investigated. In aqueous
      media Pummerer's ketone (I) was the dominating product but in organic media the
      product distribution was quite different; 2,2'-dihydroxy-5,5'-dimethyldiphenyl
      (II) was the main low molecular weight product. Similar product distributions
      were obtained with peroxidase adsorbed on a solid support and suspended in
      toluene and with peroxidase solubilized in a microemulsion containing the same
      solvent. The best selectivity for the formation of (II) was obtained when the
      enzyme was adsorbed on Celite and suspended in water-saturated chloroform with
      0.5% (v/v) extra water added. The yield of low molecular weight products in this
      case was 28%; of this fraction, 95% was (II).

PMID- 1366749
TI  - Effects of lipids on thermophilic anaerobic digestion and reduction of lipid
      inhibition upon addition of bentonite.
AB  - The effect of bentonite-bound oil on thermophilic anaerobic digestion of cattle
      manure was investigated. In digestor experiments, addition of oil was found to be
      inhibitory during start-up and the inhibitory effect was less pronounced when the
      oil was added in the form of bentonite-bound oil compared to when the oil was
      added alone. After adaptation of the digestors, very rapid degradation of oil was
      observed and more than 80% of the oil was degraded within a few hours after daily
      feeding. In batch experiments, glyceride trioleate was found to be inhibitory to
      thermophilic anaerobic digestion when the concentrations were higher than 2.0
      g/l. However, addition of bentonite (a clay mineral) at concentrations of 0.15%
      and 0.45% was found to partly overcome this inhibition. Addition of calcium
      chloride in concentration of 3 mM (0.033% w/v) showed a similar positive effect
      on the utilization of oil, but the effect was lower than with bentonite.

PMID- 1366751
TI  - Laboratory waste management: a significant concern.

PMID- 1366750
TI  - Modified fiberglass support for microsequence analysis of proteins and peptides.

PMID- 1366752
TI  - Simplifying sterile access in bioreactor operations.

PMID- 1366753
TI  - A control for fetal bovine serum.
AB  - The FBS Control is designed to assist cell culture scientists who have been
      frustrated with lack of consistency in FBS lots. Continued use will reduce the
      time and expense needed in classical lot selection methods.

PMID- 1366754
TI  - A vacuum-controlled pump for peptide production.

PMID- 1366755
TI  - Spin filter technology: advancing continuous cell culturing methodology.

PMID- 1366756
TI  - Specimen manipulation at the micron level.

PMID- 1366757
TI  - Induction and purification of kievitone hydratase from Fusarium solani f. sp.
      phaseoli.
AB  - Fusarium solani f. sp. phaseoli is capable of detoxifying the major isoflavonoid
      phytoalexins produced by its host plant Phaseolus vulgaris. One of the enzymic
      activities involved is kievitone hydratase (KHase), a secreted glycoprotein which
      catalyses the conversion of kievitone to the less fungitoxic derivative,
      kievitone hydrate. Even under conditions of substrate induction, the enzyme is
      expressed at levels that are too low for satisfactory purification. Therefore,
      several other isoflavonoids were tested as inducers in culture. Among the
      phytoalexins produced by the host plant, phaseollinisoflavan was the best
      inducer, elevating the level of secreted enzyme eight-fold. Treatment with
      biochanin A, a product of chickpea, resulted in a 16-fold increase of secreted
      activity. The maximum rate of induction was observed 9-24 hr after addition of
      biochanin A, during which time several metabolites of the inducer were also
      present. KHase was purified from filtrates of biochanin A-induced cultures.
      Denaturing gel electrophoresis indicated that two species of Mr 47,000 and 49,000
      copurified with the activity. N-Terminal sequence analysis indicated that the two
      species possessed related, or identical, polypeptide moieties. Comparison with
      the size of the non-denatured enzyme, previously determined to be ca 100,000,
      indicates that its native state is a dimer.

PMID- 1366758
TI  - Carolinoside: a phytosteroidal glycoside from Solanum carolinense.
AB  - The glycoside of a new class of phytosteroids has been isolated from Solanum
      carolinense. The steroidal aglycone (carolinone) is alkylated at C-3 and is
      identified as C-[(2,4,5-trideoxy-3-keto-4,5-dehydro)-pentulopyranosyl]-(5----3)-
      (13,14- seco-14 beta,17 alpha-dihydroxy) estrogen. The hydrolytic labile glycosyl
      moiety is identified as O-(beta-D-glucopyranosyl) (1----1)-[L-(2,6-dideoxy-3-C
      methyl)- arabinopyranose]. The linkage of this disaccharide in the steroidal
      glycoside (carolinoside) is shown to be O-(alpha-pentulopyranosyl)- (1----4)-O
      (beta-L-arabinopyranosyl)-(1----1)-D-glucopyranose. Carolinoside occurs at
      concentrations of 10(-7)-10(-6) M in leaf tissue and was shown to be the host
      plant specific feeding induction factor for Manduca sexta.

PMID- 1366759
TI  - Introduction and maintenance of prokaryotic DNA in Ustilago violacea.
AB  - A strain of the basidiomycete, Ustilago violacea, was transformed with a
      prokaryotic plasmid, pMP4-1, which confers resistance to neomycin. U. violacea
      transformants were selected at a frequency of 5 per microgram pMP4-1 DNA. Such
      transformants were at least 8-fold more resistant to neomycin than was the
      untransformed recipient U. violacea. Enzyme activity associated with the neomycin
      resistance gene was also found in the transformants. Southern DNA-DNA
      hybridization detected pMP4-1-derived sequences in both nuclear and
      mitochondrially-associated DNAs from transformants. The patterns of hybridization
      suggested integration of pMP4-1 sequences into the respective genomes. DNA from
      the nuclear fraction of U. violacea transformants failed to produce E. coli
      transformants resistant to neomycin or to carbenicillin. In contrast, DNA from
      the mitochondrially-associated fraction in U. violacea transformants produced E.
      coli transformants resistant to neomycin. The E. coli transformants contained a
      pMP4-1-derivative, pWP8, which was subsequently shown by Southern blot analysis
      to harbor U. violacea mitochondrial DNA. Thus, a prokaryotic plasmid can be used
      to transform the eukaryote U. violacea and acquire endogenous sequences from this
      organism.

PMID- 1366760
TI  - CP-60,993, a new dianemycin-like ionophore produced by Streptomyces hygroscopicus
      ATCC 39305: fermentation, isolation and characterization.
AB  - CP-60,993, 19-epi-dianemycin, is a novel polycyclic ether antibiotic produced by
      Streptomyces hygroscopicus ATCC 39305. Fermentation recovery, purification and
      crystallization were achieved using standard procedures. CP-60,993 was
      characterized as a monocarboxylic acid. Elemental analysis suggested a molecular
      formula of C47H78O14 for the free acid and C47H77O14 Na for the sodium salt.
      Crystalline from CP-60,993 sodium salt shows the following properties: m.p. 193
      205 degrees C, E1%(1 cm) = 157 at 232 nm, [alpha]25 degrees C(D) + 11.0 (c 1,
      methanol). The structure, determined by MS, PMR and CMR, differs from dianemycin
      only in the stereochemistry at position 19. This was confirmed by X-ray
      crystallography carried out on the rubidium salt of CP-60,993. It exhibited
      activity in vitro against Gram-positive and anaerobic bacteria, efficacy against
      Eimeria coccidia in vivo in poultry, and stimulation in vitro of rumen propionic
      acid production.

PMID- 1366761
TI  - Sizing biological samples by photosedimentation techniques.
AB  - The performance of the Joyce-Loebl disk centrifuge in the sizing of Escherichia
      coli cells, protein inclusion bodies, and cell debris is evaluated. The need for
      a density gradient that extends throughout the entire spin fluid is highlighted,
      and a set of standard conditions that fulfill this requirement is defined. E.
      coli cells experience a reduction in their Stokes diameter when exposed to
      ethanol, indicating that a spin-buffer fluid combination such as glycerol-water
      is to be preferred for the sizing of bacteria. The instrument baseline is
      influenced by the presence of particles, and a method of estimating the baseline
      is described. The sizing of small particles is further complicated by baseline
      drift due to temperature sensitivity of the optical yoke. An analysis of
      diffusion in the spin fluid is conducted, and an expression for the
      sedimentation:diffusive flux ratio is derived. For the current samples, it is
      shown that diffusion within the spin fluid does not lead to significant errors
      for 0.15-microns particles, whereas the phenomenon may be significant at the
      manufacturer's size limit of 0.01 micron.

PMID- 1366762
TI  - Enhancing oxygen transfer in surface-aerated bioreactors by stable foams.
AB  - To enhance oxygen transfer in surface-aeration bioreactors, stabilized foams were
      generated to increase the gas-liquid interfacial area by slowly introducing
      coarse bubbles into media containing fetal bovine serum. The bubble sparging
      rates were so low (i.e., 20 and 50 mL/h) that the contribution to oxygen transfer
      from these bubbles was due to foaming instead of bubbling. Furthermore, no
      physical cell damage caused by bubble sparging was observed. Oxygen transfer
      coefficients, kLa, in the bioreactors were measured in cell-free media. Without
      the foam-stabilizing agent (i.e., serum), no appreciable change in kLa was
      observed due to the bubble sparging. On the other hand, with serum, kLa increased
      with increasing serum content and bubble sparging rate and corresponded well with
      the degree of foaming. With 10% fetal bovine serum and a bubble sparging rate of
      50 mL/h, kLa increased approximately 90% compared with no foaming. The enhancing
      effect of foam on oxygen transfer in surface aeration bioreactors has been
      further demonstrated with hybridoma cultures simultaneously grown in three
      identical bioreactors with and without stabilized foams.

PMID- 1366763
TI  - Representation of phase equilibrium behavior of antibiotics.
AB  - The phase equilibrium behavior of biomolecules is important both in understanding
      the partition mechanisms and in the design and optimization of downstream
      recovery processes. Chen et al. (1989) proposed a molecular thermodynamic
      framework that successfully represents the liquid-solid equilibrium behavior of
      amino acids and small peptides as functions of temperature, ionic strength,
      solvent compositions, and pH. Based on this theoretical framework, this paper
      presents recent results in representing the liquid-solid equilibrium behavior
      (solubilities) and the liquid-liquid equilibrium behavior (phase partitioning) of
      beta-lactam antibiotics, which are amino acid derivatives and important
      chemotherapeutic agents.

PMID- 1366765
TI  - Electrospray ionization mass spectrometry--a powerful new analytical tool.

PMID- 1366764
TI  - Precipitation of nucleic acids with poly(ethyleneimine).
AB  - Removal of nucleic acids from cell extracts is a common early step in downstream
      processing for protein recovery. We report on the precipitation of nucleic acids
      from a homogenate of Saccharomyces cerevisiae by addition of the cationic
      polyelectrolyte poly(ethyleneimine) (PEI), focusing on the effect of PEI dosage
      on particle size, protein loss, and extent of nucleic acid removal in both batch
      and continuous mode. Better than 95% removal of nucleic acids from yeast
      homogenates was achieved by means of precipitation with PEI with protein losses
      of approximately 15% with or without previous removal of cell debris. The
      coprecipitated protein is predominately large molecular weight material and
      exhibits both low and high isoelectric points. Such treatment does not aggregate
      the cell debris; size distribution of the precipitated particles from a
      continuous precipitator is very similar to that for protein precipitation.

PMID- 1366766
TI  - Training neural networks to analyse biological sequences.

PMID- 1366767
TI  - The biological production of protein polymers and their use.

PMID- 1366768
TI  - Pandora's communications?

PMID- 1366769
TI  - Moving lectures at the Protein Society meeting, 1990.

PMID- 1366770
TI  - The International Centre for Genetic Engineering and Biotechnology of UNIDO.

PMID- 1366771
TI  - The International Institute of Biotechnology.

PMID- 1366772
TI  - An overview of biotechnology information resources.

PMID- 1366774
TI  - Bioreactor integration with downstream processing.

PMID- 1366773
TI  - Detection of genetically engineered traits among bacteria in the environment.
AB  - The release of genetically engineered microorganisms (GEMs) into the environment
      has, as its main aims, the benefits of improved agricultural yield and control of
      environmental pollution. However, effective and safe release programmes
      necessitate the development of sensitive, selective detection methods to monitor
      the environmental impact of released organisms.

PMID- 1366775
TI  - Toward a unified approach to genetic mapping of eukaryotes based on sequence
      tagged microsatellite sites.
AB  - The genomes of all eukaryotes appear to contain a special class of loci, termed
      microsatellites, which can serve, if sequenced and taken as the substrate for the
      polymerase chain reaction, as highly informative, locus-specific markers. By
      analogy to the "sequence tagged sites" recently proposed by Olsen et al. for
      standardizing the human physical gene map, these microsatellite markers are
      termed "sequence tagged microsatellite sites" (STMS). Genetic maps based on STMS
      will share with the Olsen physical maps the advantage that mapping vocabularies
      will be standardized to the DNA sequence base and that access to any particular
      locus will not require shipping or storing cloned probes. The species map will
      consist simply of a listing of nucleotide sequences. Reference populations for
      developing STMS maps can be chosen on the basis of biological or economic
      interest. It will not be necessary to maximize for genetic divergence.

PMID- 1366776
TI  - Rattlesnake and scorpion antivenoms from the egg yolks of immunized hens.
AB  - Antivenoms used to treat poisonous bites and stings are usually derived from
      horse sera. Consequently, they contain horse immunoglobulins, which frequently
      cause complement mediated side effects, and other proteins that can cause serum
      sickness and, occasionally, anaphylactic shock. Here we describe a new, avian
      source of antivenoms that precludes these complications, and an efficient and
      gentle means for preparing antivenoms composed solely of venom-specific
      antibodies. We demonstrate that antivenoms purified from the egg yolks of laying
      hens immunized with Crotalus atrox rattlesnake venom and Leiurus quinquestriatus
      hebraeus scorpion venom neutralize the lethal effects of these venoms in vivo.
      Antivenoms purified from chicken eggs may be pharmaceutically safer and more
      economical to produce than current horse antivenoms.

PMID- 1366777
TI  - Insect resistant cotton plants.
AB  - We have expressed truncated forms of the insect control protein genes of Bacillus
      thuringiensis var. kurstaki HD-1(cryIA(b) and HD-73 (cryIA(c) in cotton plants at
      levels that provided effective control of agronomically important lepidopteran
      insect pests. Total protection from insect damage of leaf tissue from these
      plants was observed in laboratory assays when tested with two lepidopteran
      insects, an insect relatively sensitive to the B.t.k. insect control protein,
      Trichoplusia ni (cabbage looper) and an insect that is 100 fold less sensitive,
      Spodoptera exigua (beet armyworm). Whole plants, assayed under conditions of high
      insect pressure with Heliothis zea (cotton bollworm) showed effective square and
      boll protection. Immunological analysis of the cotton plants indicated that the
      insect control protein represented 0.05% to 0.1% of the total soluble protein. We
      view these results as a major step towards the agricultural use of genetically
      modified plants with insect resistance in this valuable, high acreage crop.

PMID- 1366778
TI  - New frontiers for mass spectrometry.

PMID- 1366779
TI  - Small molecules, large molecules, and the new biotechnology.

PMID- 1366780
TI  - Effect of intercalating dyes on the production of antibiotics by Micromonospora
      rosaria and Micromonospora purpurea.
AB  - The effect of treatment with various intercalating dyes on the ability to produce
      antibiotics in Micromonospora rosaria and Micromonospora purpurea was studied.
      Treatment with acriflavine resulted in a high frequency loss of antibiotic
      productivity in both species. In M. rosaria, the loss of antibiotic-producing
      ability appeared to be strain-dependent. In M. purpurea, up to 90% of colonies
      were found to have lost gentamicin-producing ability when protoplasts were used
      in the test. These antibiotic-nonproducing strains were further studied. The
      following observations were made: (1) Unlike the producing ability, the
      resistance to the antibiotics is a very stable character in both species. (2)
      Protoplast fusion analysis indicates that rosamicin-nonproducing characteristics
      of MR 217-AF2 and MR 217-AF3 strains induced by the acriflavine treatment is due
      to chromosomal mutation or rearrangement but not to loss of a plasmid. (3)
      Gentamicin-nonproducing strains of M. purpurea responded differently to the
      supplementation of streptamine or DOS in the culture medium. When supplemented
      with streptamine or DOS, some of these strains regained the ability to produce
      antibiotic, showing that the biosynthesis of intermediate was affected in these
      strains.

PMID- 1366781
TI  - Flow cytometric study of hybridoma cell culture: correlation between cell surface
      fluorescence and IgG production rate.
AB  - Flow cytometry was applied to measure the fluorescence of IgG molecules on
      hybridoma cell surface stained with FITC-conjugated anti-mouse IgG F(ab')2. Using
      light scattering to exclude the dead cell population from the analysis, the
      surface fluorescence intensity allows for the differentiation between producing
      and nonproducing cells. A linear correlation has been found between the intensity
      of mean surface fluorescence of the cell population and the specific antibody
      production rate.

PMID- 1366782
TI  - Coenzymatic properties of low molecular-weight and macromolecular N6-derivatives
      of NAD+ and NADP+ with dehydrogenases of interest for organic synthesis.
AB  - The catalytic activity, expressed as Km and Vmax values, of 16 enzymes of
      practical interest with the macromolecular coenzymes poly(ethylene glycol)-N6-(2
      aminoethyl)-NAD+ and poly(ethylene glycol)-N6-(2-aminoethyl)-NADP+ and their low
      molecular weight precursors N6-(2-aminoethyl)-NAD+ and N6-(2-aminoethyl)-NADP+,
      was investigated. The enzymes examined are of direct interest for organic
      synthesis (i.e. alcohol dehydrogenase from yeast, horse liver, or
      Thermoanaerobium brockii, lactic dehydrogenase, and several hydroxysteroid
      dehydrogenases) or are used for the regeneration of NAD+, NADP+, NADH, or NADPH
      (i.e. glutamate dehydrogenase from liver or Proteus, formate dehydrogenase,
      glucose dehydrogenase, and malic enzyme). The cycling efficiency of poly(ethylene
      glycol)-N6-(2-aminoethyl)-NADP+ was examined with coupled-enzymes or coupled
      substrates systems. Poly(ethylene glycol)-N6-(2-aminoethyl)-NAD+ and, even more
      so, poly(ethylene glycol)-N6-(2-aminoethyl)-NADP+ were excellent coenzymes with
      several dehydrogenases. In addition, the coenzymatic properties of N6-(3
      sulfonatopropyl)-NAD+, an NAD+ derivative carrying a strong anionic group, were
      compared with those of the newly synthesized N6-(2-hydroxy-3-trimethylammonium
      propyl)-NAD+, an NAD+ derivative carrying a strong cationic group. It was
      expected that the presence of the sulfonic or quaternary ammonium group would
      enhance the residence time of the coenzyme inside continuous-flow reactors if
      membranes with anionic or cationic groups, respectively, were used.

PMID- 1366783
TI  - Recovery of a foreign protein from the periplasm of Escherichia coli by chemical
      permeabilization.
AB  - We have applied the technique of protein release by chemical permeabilization to
      recover a foreign protein in active form from the periplasm of a recombinant
      strain of Escherichia coli. The two agents used in our chemical permeabilization
      scheme, guanidine hydrochloride and Triton X-100, have different modes of action,
      allowing selectivity in protein release based on intracellular location under
      different treatment conditions. Specifically, treatment of E. coli C600-1 cells
      by guanidine alone resulted in 40-fold purification of recombinant beta
      lactamase, which is periplasmically expressed in this host. Achieving such high
      purification in the cell disruption stage could alleviate some of the problems
      associated with recovery of intracellular products, such as low expression or the
      need to solubilize cytoplasmic inclusion bodies. Recovery of periplasmic proteins
      by chemical permeabilization is simpler than by osmotic shock and is less
      expensive than using enzymatic digestion.

PMID- 1366785
TI  - Arthur Webster Pty Ltd.

PMID- 1366784
TI  - Penicillin acylase mutants with altered site-directed activity from Kluyvera
      citrophila.
AB  - Oligonucleotide-directed mutagenesis has been used to obtain specific changes in
      the penicillin acylase gene from Kluyvera citrophila. Wild-type and mutant
      proteins were purified and the kinetic constants for different substrates were
      determined. Mutations in Met168 highly decreased the specificity constant of the
      enzyme for penicillin G, penicillin V and phenylacetyl-4-aminobenzoic acid and
      the catalytic constant kcat for phenylacetyl-4-aminobenzoic acid. Likewise, the
      phenylmethylsulphonyl-fluoride sensitivity was significantly decreased. It is
      concluded that the 168 residue is involved in binding by interaction with the
      acid moiety of the substrate. A putative penicillin-binding domain was located in
      penicillin acylase by sequence homology with other penicillin-recognizing
      enzymes. Lys374 and His481, the conserved amino acid residues that are essential
      for catalysis in these enzymes, can be changed in penicillin acylase with no
      changes to the kcat and phenylmethylsulphonyl fluoride reactivity, but change the
      Km. The likelihood of the existence of this proposed penicillin binding site is
      discussed. The reported results might be used to alter the substrate specificity
      of penicillin acylase in order to hydrolyse substrates of industrial significance
      other than penicillins.

PMID- 1366786
TI  - Measurement of counting efficiencies with solid scintillators: a receptor assay
      example.

PMID- 1366787
TI  - Luer tip quick antibody purification by affinity chromatography.

PMID- 1366788
TI  - Biological freezer temperature monitor.

PMID- 1366789
TI  - HPLC sample pretreatment and preparation.

PMID- 1366790
TI  - 1990 compensation survey.

PMID- 1366791
TI  - The Cetus experience: troubles with clinical trials design & data presentation.

PMID- 1366792
TI  - The food safety of transgenic animals.

PMID- 1366793
TI  - Entrapment vectors: a new tool for mammalian genetics.
AB  - The use of mouse embryonic stem (ES) cells has facilitated the creation of mouse
      strains carrying desired genetic alterations. Recently, "entrapment" vectors have
      been developed to identify and mutate genes active during embryogenesis. These
      vectors in combination with ES cells may provide an efficient screening strategy
      to find genes that control mouse development.

PMID- 1366794
TI  - Inheritance and expression of chimeric genes in the progeny of transgenic maize
      plants.
AB  - We obtained transgenic maize plants by using high-velocity microprojectiles to
      transfer genes into embryongenic cells. Two selectable genes were used to confer
      resistance to either chlorsulfuron or phosphinothricin, and genes encoding either
      E. coli beta-glucuronidase or firefly luciferase were used as markers to provide
      convenient assays for transformation. When regenerated without selection, only
      two of the eight transformed embryogenic calli obtained produced transgenic maize
      plants. With selection, transgenic plants were obtained from three of the other
      eight calli. One of the two initial lines produced 15 fertile transgenic plants.
      The progeny of these plants contained and expressed the foreign genes. Luciferase
      expression could be visualized, in the presence of added luciferin, by overlaying
      leaf sections with color film.

PMID- 1366795
TI  - A new vector for cloning large eukaryotic DNA segments in Escherichia coli.
AB  - We investigated the relationship between plasmid size and electroporation
      efficiency in E. coli and found that even very large plasmids can be transfected
      efficiently. The efficiencies are well above the minimum required to construct
      representative libraries of complex eukaryotic genomes. To exploit this
      observation we constructed a novel mammalian-E. coli shuttle vector whose
      replication in E. coli is driven by the F sex factor episome origin. This new
      vector system should accept inserts well in excess of 100 kb, thus putting the
      cloning of mammalian genes by direct phenotypic complementation within reach.

PMID- 1366796
TI  - Expression of intracellular hemoglobin improves protein synthesis in oxygen
      limited Escherichia coli.
AB  - We have previously cloned the Vitreoscilla hemoglobin gene (VHb) and expressed
      the protein in Escherichia coli in its active form. Under oxygen-limited
      conditions the presence of VHb improves protein synthesis as indicated by both
      total protein content and the activity of an enzyme expressed from a cloned gene
      present on a multicopy plasmid. Measurements of nitrogen utilization rates
      corroborate the observation of enhanced protein synthesis; however, the rates of
      carbon consumption and acid synthesis remain unchanged. This suggests that the
      net effect of VHb in E. coli is to improve the efficiency, rather than the
      kinetics, of oxygen-limited aerobic metabolism. We propose two possible models
      for the mechanism of action of VHb: the facilitated diffusion hypothesis and the
      intracellular redox effector hypothesis. These suggest other systems in which
      cloned VHb may enhance bioprocess productivity.

PMID- 1366797
TI  - Cell culture on a thermo-responsive polymer surface.
AB  - We have used a thermo-responsive polymer, poly-N-isopropyl acrylamide (PNI-PAAm),
      as a substratum for the culture of human dermal fibroblasts by conjugating it
      with collagen. The cells attached well, spread, and grew on the substratum,
      indicating that the polymer has no toxicity towards the cells. PNIPAAm is
      insoluble in water over the lower critical solution temperature (LCST; about 32
      degrees C) and reversibly solubilized below the LCST. Taking advantage of this
      conversion, monolayered fibroblasts cultured on the substratum containing the
      PNIPAAm over the LCST, were completely detachable from the substratum by simply
      lowering the temperature below the LCST, without the use of conventional
      detaching agents such as trypsin and EDTA. The detached cell sheet gradually
      aggregated and finally formed a multicellular spheroid. This polymer may provide
      a convenient and potentially useful technology for cell culture.

PMID- 1366798
TI  - Affinity innovations for bioprocessing.

PMID- 1366799
TI  - Development of a chromatographic process for large-scale purification of
      staphylococcal enterotoxin B.
AB  - A process for large-scale purification of staphylococcal enterotoxin B (SEB) is
      presented. The process consists of three chromatographic steps. The first two
      steps are based on ion-exchange chromatography and the final one on gel
      filtration. Diluted culture supernatant (2000 dm3) with a SEB content of 0.4 mg
      dm-3 were processed and purified. SEB was obtained in 1.5 dm3 of 0.1 mol dm-3
      ammonium hydrogen carbonate buffer, pH 8.0. The final product produced a single
      band on SDS polyacrylamide gel electrophoresis and a single peak when subjected
      to analytical gel filtration. The overall recovery was 74%.

PMID- 1366800
TI  - Ammonium effects on streptonigrin biosynthesis by Streptomyces flocculus.
AB  - A defined medium containing glucose and ammonium as the sole carbon and nitrogen
      sources was developed to support growth and streptonigrin production. In this
      defined medium, increased initial levels of ammonium resulted in increased growth
      suggesting that nitrogen is the growth limiting nutrient. In some cases,
      increased initial ammonium levels resulted in decreased specific streptonigrin
      productivity, suggesting that nitrogen regulatory mechanisms may adversely affect
      streptonigrin biosynthesis. This suggestion that nitrogen regulation adversely
      affects antibiotic biosynthesis is further supported by results from two studies
      in which the ammonium supply to the cells was controlled. In the first study,
      streptonigrin productivity and final titer were enhanced by the addition of an
      ammonium trapping agent. In the second experiment, when ammonium chloride was fed
      slowly throughout the course of cultivation, the production phase was lengthened
      and the maximum antibiotic concentration was enhanced compared to the batch
      controls containing either the same initial or the same total ammonium chloride
      levels. Although our results indicate streptonigrin production may be subject to
      nitrogen regulatory mechanisms, the effect of nitrogen on streptonigrin
      production cannot be strictly correlated to the extracellular ammonium
      concentration. In fact, we observed that when ammonium was depleted from the
      medium, streptonigrin production ceased.

PMID- 1366801
TI  - Evaluation of infrared spectroscopy as a bacterial identification method.
AB  - A study motivated by the recent revival of interest in the use of IR spectroscopy
      to identify bacteria is reported. A library of FT-IR spectra of dried bacterial
      films was complied using 16 different strains. A test set was compiled from
      spectra of the same strains grown several months later. The test set was
      quantitatively compared with the library on the basis of spectral similarity in
      the region 980-1190 cm-1. Six of the strains in the test set were not matched
      with the correct strain in the library despite efforts to reproduce the
      conditions under which cells were grown and prepared. The results suggest that
      reproducibility of the bacterial spectra is a potential difficulty that must be
      addressed by any attempts to develop FT-IR spectroscopy as a bacterial
      identification method.

PMID- 1366802
TI  - Optimization of the hardening treatment of S. cerevisiae bioparticles.
AB  - Immobilization of microorganisms for application in fermentation processes
      generates bioparticles whose mechanical properties can be greatly improved if
      they are subjected to a hardening process. In this work, the immobilization of
      Saccharomyces cerevisiae in K-carrageenan and their treatment with Al(NO3)3 as
      hardening agent have been optimized. The effect of several factors have been
      studied, including the cell concentration in the gel, the concentration of
      hardener, and time of contact of this latter with bioparticles. In repeated batch
      experiments, a factorial design technique has been employed, reaching high values
      of productivity and a good retention of particles in the matrix. Once optimal
      conditions were selected, continuous experiments were realized, in which the
      hardened beads showed significant advantages, such as increase of 20% in ethanol
      productivity, a better evacuation of gas from the reactor, and a higher cell
      retention.

PMID- 1366803
TI  - Protease-catalysed peptide synthesis in aqueous-organic two-phase systems:
      reactant precipitation and interfacial inactivation.
AB  - Peptides can be efficiently synthesized by the proteases thermolysin and pepsin
      acting in aqueous-organic two-phase systems similar to those reported previously.
      However, a number of problems can prevent successful reactions in these systems,
      with these and other proteases: (1) Complexes between amino acid reactants that
      are sparingly soluble in both phases may be precipitated, though their solubility
      behavior is complex; (2) the enzyme may be subject to rapid inactivation by
      contact with the phase interface, and the rate of this is unusually dependent on
      the nature of the solvent; and (3) the reaction rate is usually slow.

PMID- 1366804
TI  - Immobilization of lipase from Candida cylindraceae and its use in the synthesis
      of menthol esters by transesterification.
AB  - Lipase (EC 3.1.1.3) from Candida cylindraceae has been immobilized by the
      cellulose-titanium chloride method, and on EP-400 polyethylene, with and without
      glutaraldehyde crosslinking, to give active preparations when assessed by their
      ability to catalyse the hydrolysis of tributyrin. In both cases, the use of
      glutaraldehyde crosslinking was shown to improve the stability of the
      preparations for repeated use. The lipase immobilized on EP-400 polyethylene was
      found to be effective in transesterification using tributyrin or triacetin as
      acyl donors with l-menthol as acceptor. The production of methyl butanoate and of
      methyl acetate using this immobilized preparation was in each case enhanced in
      the presence of Amberlite IR 47 Anion exchange resin (OH form).

PMID- 1366805
TI  - Microbial sensor for penicillins using a recombinant strain of Escherichia coli.
AB  - E. coli harboring the multicopy plasmid pBR327, which codes for beta-lactamase
      synthesis, was immobilized on acetylcellulose membranes. These were placed in the
      vicinity of a flat pH electrode, thus constituting a penicillin biosensor based
      on the detection of changes in pH using a reference pH electrode. A response time
      of 8 min was obtained with at least 2 mg of cells cm-2 of membrane. A linear
      detection range between 5 and 30 mM of penicillin was achieved. Buffering
      capacity decreased the sensitivity, but to a lower extent as when compared with
      probes using purified enzyme. The sensor was completely stable for at least 13
      days and proved to be useful for penicillin estimation in complex media such as
      fermentation broths and milk.

PMID- 1366806
TI  - Harvesting recombinant microbial cells using crossflow filtration.
AB  - A contained, crossflow filtration (CFF) membrane system is described for
      harvesting Saccharomyces cerevisiae and Escherichia coli cells. This system is
      portable and can be cleaned and sanitized in place. Low- and high-cell density
      (LCD, HCD) fermentations of recombinant cells in 10- to 200-l volumes were used
      as the starting material. LCD fermentations, up to 8.3 g l-1 dry weight (dcw) of
      S. cerevisiae, with volumes of 10 to 200 l were harvested and diafiltered in 0.5
      and 1.5 h, respectively. HCD 200-l fermentations of S. cerevisiae (47-63 g l-1
      dcw) were harvested and diafiltered in approximately 2 h. E. coli fermentations,
      LCD and HCD (up to 16.2 g l-1 dcw), of 200-l volumes were harvested and
      diafiltered in 2.3 h while employing 14 and 75 ft2 of membrane area,
      respectively. Using hollow fiber or flat sheet membranes from different sources,
      cell harvesting times were less than 2.5 h. These studies demonstrate that CFF is
      an efficient method for harvesting and diafiltering recombinant S. cerevisiae and
      E. coli cells from fermentation broth.

PMID- 1366807
TI  - Electroporation and expression of the broad host-range plasmid pRK2501 in
      Azotobacter vinelandii.
AB  - Azotobacter vinelandii cells were transformed via high-voltage electroporation,
      with the broad host-range plasmid pRK2501. The number of transformants was
      dependent on the applied voltage, capacitance, and recovery procedure after
      electroporation. For example, Log, 4.44 transformants microgram-1 DNA were
      recovered in the A. vinelandii cell suspension electroporated at 1500 V and 25
      microF capacitance (time constant 29.0 ms) and recovered on LB agar amended with
      0.5 microgram/ml-1 kanamycin (pRK2501 encodes for both kanamycin and tetracycline
      resistance). Electroporation at 2500 V and capacitance settings of 25 and 3
      microF did not produce any transformants. Cell survival was also poor at high
      voltages. A. vinelandii transformants were not recovered on N-free agar medium.
      In addition, no viable cells were recovered on N-free agar after electroporation
      at 2500 V, 25 microF; 2500 V, 3 microF; and 1500 V, 25 microF. Electroporation
      may be a useful method to genetically transform Azotobacter species for use in
      physiological and/or genetic studies.

PMID- 1366808
TI  - Endoglucanase E, produced at high level in Escherichia coli as a lacZ' fusion
      protein, is part of the Clostridium thermocellum cellulosome.
AB  - The Clostridium thermocellum celE gene was expressed at high level in Escherichia
      coli TG1 when placed under the transcriptional and translational control of lacZ'
      in pUC18; in the presence of a multicopy plasmid (pNM52) containing the lacIq
      gene, expression of full-length and truncated forms of celE was regulated by
      isopropyl-beta-D-thiogalactopyranoside. Catalytically active endoglucanase E
      (EGE) produced by E. coli was subject to proteolytic processing. The main protein
      species produced from full-length and truncated forms of celE was around 40 kDa
      in size and had an N-terminal amino acid sequence corresponding to that derived
      for mature EGE from the nucleotide sequence; in addition, larger species of about
      75 kDa, presumably corresponding to full-size EGE, were produced by E. coli
      containing the full-length celE gene. Even after removal of the signal peptide
      sequence, EGE produced by E. coli was secreted into the periplasm. Up to 157 bp
      could be deleted from the 5' end of the celE gene without affecting the catalytic
      activity of EGE produced by E. coli. A polypeptide of Mr 86 kDa, immunoreactive
      with anti-EGE antiserum, was demonstrated in the high-molecular-weight, cellulose
      binding multiprotein aggregate recoverable from C. thermocellum culture
      supernatant.

PMID- 1366809
TI  - Growth and product inhibition kinetics of T-cell hybridomas producing lymphokines
      in batch and continuous culture.
AB  - The kinetics of growth and lymphokine formation by T-cell hybridomas were
      investigated in batch and continuous culture. Product inhibitions by ammonia and
      lactic acid were considered in the proposed model and experimental data were used
      to determine the kinetic and inhibition constants. The effect of dilution rate on
      specific substrate consumption and product formation rates was investigated.

PMID- 1366810
TI  - Transient behavior of T-cell hybridomas in response to changes in metabolite
      concentrations in continuous culture.
AB  - Effects of pulse and step changes in major metabolite concentrations such as
      glucose, glutamine, lactic acid, and ammonium on behavior of T-cell hybridomas in
      continuous culture were investigated in order to develop a strategy to maximize
      specific rate of lymphokine formation. Step increases in glucose, lactic acid,
      and ammonium concentrations decreased, and a step increase in glutamine
      concentration increased, the specific rate of lymphokine formation. Effects of
      step and pulse changes on specific rates of glucose and glutamine consumption and
      viability of cells were also investigated.

PMID- 1366811
TI  - Immobilization of the surfactant-degrading bacterium Pseudomonas C12B in
      polyacrylamide gel beads: I. Effect of immobilization on the primary and ultimate
      biodegradation of SDS, and redistribution of bacteria within beads during use.
AB  - The surfactant-degrading bacterium Pseudomonas C12B was immobilized in
      polyacrylamide gel beads. Conditions were established for minimizing the apparent
      loss of sodium dodecyl sulfate (SDS)-degrading activity accompanying
      polymerization, while still retaining durable gel beads. Apparent losses in SDS
      degrading activity compared with free untreated bacteria were attributed largely
      to substrate diffusion limitations imposed by the gel matrix. Changes in the rate
      and extent of conversion of radiolabel from [1-14C]SDS to 14CO2 were attributed
      to diffusional restrictions on O2 availability within the gel beads. Scanning
      electron microscopy was used to show that beads (3 mm3) repeatedly exposed to SDS
      for 35 days contained a high cell density in a sub-surface layer 0.4-0.7 mm deep,
      with relatively few bacteria either at greater depth or at the bead surface.

PMID- 1366812
TI  - Immobilization of microbial cells by adsorption.
AB  - Immobilized cells cover a wide area of applications and are essential components
      of many biotechnological processes. In general it can be distinguished between
      two immobilization methods: (1) entrapment into polymers and (2) natural
      adsorption onto porous and inert support materials. The immobilization by
      adsorption is discussed by the following criteria: biomass loading, strength of
      adhesion, enzymatic stability/specific activity of the biocatalyst,
      effectivity/reaction engineering and operational stability.

PMID- 1366813
TI  - Construction of vector of Brevibacterium lactofermentum and study of its
      stability in continuous culture.
AB  - A 5.7-kb vector plasmid pBK2 was constructed by ligating the kanamycin resistance
      gene from Escherichia coli plasmid pACYC177 to an endogenous cryptic 4.4-kb
      plasmid of Brevibacterium lactofermentum ATCC 21086. The vector replicates
      efficiently and is stably maintained in the host and other coryneforms. However,
      the copy number varied from 50 to 10 per chromosome-equivalent under different
      culture conditions. Continuous culture studies showed instability when low
      dilution rates were used. Co-culture experiments were performed at various
      dilution rates to measure the growth rate ratio (alpha) of the plasmid-free cells
      to the plasmid-containing cells. It was observed that at low dilution rates the
      value of alpha was higher than that at high dilution rates. Thus, the instability
      of the plasmid can be attributed to the increase in alpha at low dilution rates.
      Modelling of instability using a random partitioning model of plasmid segregation
      and experimentally obtained values of alpha showed agreement with experimental
      data. This demonstrated that active partitioning is not the operative mechanism
      for plasmid segregation in this case.

PMID- 1366814
TI  - Two-stage cultivation of Digitalis lanata cells: semicontinuous production of
      deacetyllanatoside C in 20-litre airlift bioreactors.
AB  - A two-stage cultivation method was employed to develop a semicontinuous
      biotransformation process for the production of deacetyllanatoside C, a
      cardenolide of the important digoxin series. Digitoxin was used as the substrate
      for biotransformation. The process was optimized in 1-l shake flasks and then
      established on the 20-l scale using two airlift bioreactors, one for cell growth
      (working volume 12 litres) and another for deacetyllanatoside C production
      (working volume 18 litres). Growth and production phases were synchronized and
      the process finally ran semicontinuously in 7-d cycles. Six consecutive
      production runs were performed yielding a total of 43.8 g deacetyllanatoside C.

PMID- 1366815
TI  - Environmental carcinogenesis and biotechnology.
AB  - Numerous environmental and host factors, some of which are known and some
      unknown, contribute to cancer development. While data and studies abound, our
      current understanding of the relation between cancer and the environment is still
      very limited. Understanding environmental carcinogenesis is critical to its
      effective management. Biotechnology has revolutionalized the study of biological
      and biomedical sciences. This minireview provides an overview of environmental
      carcinogenesis with emphasis on the contributions and prospects of biotechnology
      in advancing an understanding of environmental carcinogenesis for its prevention
      and intervention.

PMID- 1366816
TI  - Mechanisms and kinetics of monoclonal antibody synthesis and secretion in
      synchronous and asynchronous hybridoma cell cultures.
AB  - The kinetics of monoclonal antibody synthesis and secretion have been studied in
      synchronous and asynchronous mouse hybridoma cell cultures. Pulse-labelling of
      IgG followed by immunoprecipitation and quantitation of synthesized and secreted
      IgG in synchronous cultures show maximum production during G1/S phases. Secretion
      takes place through exocytotic release of vesicle contents. Pulse-chase
      experiments show that 71% of the synthesized IgG is secreted within 8 h of the
      pulsing period and only a further 4% is secreted by 22 h. Higher specific
      antibody production (QA) is obtained if (a) cells are arrested and then
      maintained in G1/S phases, (b) viability is decreased during the death phase of
      batch culture, (c) the dilution rate is decreased in continuous culture or (d)
      cells are subjected to hydrodynamically induced stress. The increase in QA in all
      these cases is mainly due to the passive release of the accumulated intracellular
      antibody. DNA and protein synthetic activity peak during the early exponential
      phase and decline rapidly during mid and late exponential and death phases.
      Metabolic activity however peaks up to 20 h after the peak in DNA synthesis, and
      declines similarly during the death phase. The data are consistent with the idea
      that slow growth and higher death rates increase QA and that Ig secretion is
      probably subject to complex intracellular control.

PMID- 1366817
TI  - Hyperproduction of a bifunctional hybrid protein, metapyrocatechase-protein A, by
      gene fusion.
AB  - A hybrid protein between metapyrocatechase and Staphylococcal protein A was
      produced by recombinant DNA techniques. A plasmid carrying the fusion gene that
      encodes the hybrid protein was constructed and expressed in E. coli. Over 70% of
      soluble proteins of the cell extracts was estimated to be the hybrid protein.
      This fusion protein is about 65,000. Both the IgG-binding activity of protein A
      and the metapyrocatechase activity were found in the hybrid protein. The optimum
      pH of metapyrocatechase in the fusion protein was at around 6.5 and Km was 1.3 X
      10(-5) M. A simple immuno-enzymometric assay was developed for anti-BSA antibody
      using the fusion protein.

PMID- 1366818
TI  - An overview and historical perspective of protein biotechnology.

PMID- 1366819
TI  - Large-scale production of recombinant proteins: human leukocyte interferon.

PMID- 1366820
TI  - Production of human calcitonin by recombinant DNA technology.

PMID- 1366821
TI  - Structural analysis of proteins.

PMID- 1366822
TI  - Chemical synthesis of peptides.

PMID- 1366823
TI  - Production and analysis of proteins by recombinant DNA technology.

PMID- 1366824
TI  - Monoclonal antibodies.

PMID- 1366825
TI  - Protein biosynthesis.

PMID- 1366826
TI  - Protein purification and analysis by liquid chromatography and electrophoresis.

PMID- 1366828
TI  - Protein structure.

PMID- 1366827
TI  - Proteins as biological effectors.
AB  - This chapter presented an overview of the role of proteins as biological
      effectors. From a simplistic point of view, based solely on comparison of the
      structural diversity of immunoglobulins, blood coagulation proteins,
      gonadotropins, growth factors, and antiproteins, it could be concluded that the
      functional mechanisms of these protein families bear little or no relationship.
      Despite this enormous divergency in structure-function relationship, there are in
      fact elements of commonality in their effector roles arising as a direct
      consequence of the ability of these classes of protein effectors to act as
      exquisite examples of the processes of biorecognition. All these case histories,
      and the numerous other familial case studies of protein effectors which could
      have been employed to illustrate the different functional roles of proteins, owe
      their biological properties to their primordial protein antecedents which have
      traversed the harsh wilderness of evolution in biorecognition phenomena and
      survived to elicit specific effector roles. Dictated by underlying
      physicochemical constraints, deceived at times by the lulling tones of the siren
      entropy, and constantly vulnerable to the vagaries of other more pervasive forms
      of biological networking and information transfer encoded in the genes of virus
      and invading microorganisms, protein biorecognition in higher life forms, and
      particularly in mammals, represents the finely tuned molecular avenues for the
      genome to transfer its information to the next generation. The examples
      summarized in this chapter illustrate the complex, and in disease states
      imperfect, functional potential of proteins to be manifested in the jigsaw of
      biorecognition and be realized in the network of nature's biological effectors.
      Proteins thus represent a diverse range of effector molecules whose properties
      are totally dependent on their conformational or topographic status. The three
      dimensional structure defines active sites on the molecule through which
      intermolecular interaction and biorecognition phenomena can occur. The cipher for
      this surface topography is, of course, coded in the primary amino acid sequence.
      Much experimental work is being directed in these and other laboratories at
      elucidating the principles governing the folding of unique peptide sequences into
      three-dimensional structures. Further advances in the theoretical understanding
      of the thermodynamics of protein folding as observed by x-ray crystallography,
      nuclear magnetic resonance and other spectroscopic techniques will greatly aid
      this quest. In addition, more comprehensive computer-aided algorithms for
      structure simulation, improved models of protein conformational behavior, and
      greater insight into the molecular forces which control sequence nucleation will
      also be required.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1366829
TI  - Development of new thrombolytic agents using recombinant DNA technology.
AB  - The increasing incidence of thromboembolic diseases has sustained the search for
      new agents able to stimulate the natural fibrinolytic system. The first
      generation of antithrombotic agents include bacterial streptokinase and human
      urine urokinase. Because these molecules lack specificity for the fibrin clot,
      important efforts have been made to produce, using recombinant DNA technology,
      agents presenting higher fibrin clot selectivity such as t-PA (tissue-type
      plasminogen activator) and scu-PA (single chain urokinase-type plasminogen
      activator). In parallel, several laboratories are presently attempting to create
      mutants and hybrids plasminogen activators displaying improved thrombolytic
      properties with respect to the natural molecules. In this paper, we describe
      briefly the mechanisms of fibrinolysis and the role of the different natural
      thrombolytic agents. In addition, we review the possibilities of genetic
      engineering for the production of natural and novel plasminogen activators.

PMID- 1366831
TI  - Protecting sensitive laboratory equipment.

PMID- 1366830
TI  - Enzymatic peptide synthesis in organic media: a comparative study of water
      miscible and water-immiscible solvent systems.
AB  - Peptide synthesis was carried out in a variety of organic solvents with low
      contents of water. The enzyme was deposited on the support material, celite, from
      an aqueous buffer solution. After evaporation of the water the biocatalyst was
      suspended in the reaction mixtures. The chymotrypsin-catalyzed reaction between Z
      Phe-OMe and Leu-NH2 was used as a model reaction. Under the conditions used ([Z
      Phe-OMe]0 less than or equal to 40 mM, [Leu-NH2]0/([Z-Phe-OMe]0 = 1.5) the
      reaction was first order with respect to Z-Phe-OMe. Tris buffer, pH 7.8, was the
      best buffer to use in the preparation of the biocatalyst. In water-miscible
      solvents the reaction rate increased with increasing water content, but the final
      yield of peptide decreased due to the competing hydrolysis of Z-Phe-OMe. Among
      the water-miscible solvents, acetonitrile was the most suitable, giving 91% yield
      with 4% (by vol.) water. In water-immiscible solvents the reaction rate and the
      product distribution were little affected by water additions in the range between
      0% and 2% (vol. %) in excess of water saturation. The reaction rates correlated
      well with the log P values of the solvent. The highest yield (93%) was obtained
      in ethyl acetate; in this solvent the reaction was also fast. Under most reaction
      conditions used the reaction product was stable; secondary hydrolysis of the
      peptide formed was normally negligible. The method presented is a combination of
      kinetically controlled peptide synthesis (giving high reaction rates) and
      thermodynamically controlled peptide synthesis (giving stable reaction products).

PMID- 1366832
TI  - Optimal temperature control policy for a two-stage recombinant fermentation
      process.
AB  - The optimal temperature control policy to be followed in the operation of a two
      stage fermentation system in which gene expression is induced by a temperature
      sensitive gene switching system was studied. A genetically structured model was
      used to describe product formation, and kinetic equations based on experimental
      data were used to quantify the specific gene expression rate and parameters that
      affect plasmid instability. A constant temperature control policy and temperature
      profiling control policy including temperature cycling were studied and compared.
      Maximum average production rate was obtained from a temperature control policy in
      which the second stage was operated initially at about 40.5 degrees C and the
      temperature decreased slightly to a constant value at 40.0 degrees C. The maximum
      average production rate, which corresponds to the optimal temperature control
      policy, for an operation of 180 h was 29.7 units of protein (mg of cells)-1 h-1.

PMID- 1366833
TI  - Optimal chemostat cascades for periplasmic protein production.
AB  - This theoretical work predicts the optimal system design for the steady-state
      production of secreted protein in a chemostat cascade, using bakers' yeast
      (Saccharomyces cerevisiae) as the host organism. The protein of interest, mutant
      invertase, is secreted to the periplasmic space instead of the culture medium on
      account of its large size. This work uses the secretion model developed and
      tested by Park and Ramirez (1988). It is shown that the highest productivity is
      achieved when the chemostat cascade contains two stages, although the improvement
      over the single-stage productivity is small. When no recycle is used, the
      advantage of two stages results from the tradeoff between maximizing the cell
      concentration and maximizing the rate of protein production per cell. When
      recycle is used, the cell concentration and protein productivity are increased,
      and the advantage of two stages results from the tradeoff between maximizing the
      specific protein production rate and maximizing the specific protein secretion
      rate. Cascades with three stages were also investigated, but these were found to
      have no improvement over the corresponding two-stage cascades.

PMID- 1366834
TI  - Effects of dissolved oxygen on hybridoma cell growth, metabolism, and antibody
      production kinetics in continuous culture.
AB  - The effects of dissolved oxygen concentration (DO) on hybridoma cell physiology
      were examined in a continuous stirred tank bioreactor with a murine hybridoma
      cell line (167.4G5.3). Dissolved oxygen concentration was varied between 0% and
      100% air saturation. Cell growth and viability, carbohydrate, amino acid, and
      energy metabolism, oxygen uptake, and antibody production rates were
      investigated. Cell growth was inhibited at both high and low DO. Cells could grow
      at 0% DO and maintain viability under a nitrogen atmosphere. Cell viability was
      higher at low DO. Glucose, glutamine, and oxygen consumption rates changed little
      at DO above 1% air saturation. However, the metabolic uptake rates changed below
      1% DO, where growth became oxygen limited, and a Km value of 0.6% DO was obtained
      for the specific oxygen uptake rate. The metabolic rates of glucose, glutamine,
      lactate, and ammonia increased 2-3-fold as the DO dropped from 1% to 0%. Amino
      acid metabolism followed the same general pattern as that of glutamine and
      glucose. Alanine was the only amino acid produced. The consumption rates of amino
      acids changed little above 1% DO, but under anaerobic conditions the consumption
      rates of all amino acids increased severalfold. Cells obtained most of their
      metabolic energy from glutamine oxidation except under oxygen limitation, when
      glucose provided most of the energy. The calculated ATP production rate was only
      slightly influenced by DO and rose at 0% DO. Antibody concentration was highest
      at 35% DO, while the specific antibody production rate was insensitive to DO.

PMID- 1366835
TI  - Plant cell culture using a novel bioreactor: the magnetically stabilized
      fluidized bed.
AB  - A novel bioreactor using magnetically stabilized fluidized bed (MSFB) technology
      has been developed that has certain advantages for cultivating cells
      continuously. In this system, the cells are protected from shear and are
      constrained to move through the fermenter in lock-step fashion by being
      immobilized in calcium alginate beads. The MSFB permits good mass transfer,
      minimizes particle collisions, and allows for the production of cells while
      maintaining a controlled cell residence time. Details of the experimental system
      are described. In addition, the experimental performance of an MSFB used to grow
      plant cells in batch mode is compared to the results obtained in shake flask
      culture.

PMID- 1366836
TI  - Inclined sedimentation for selective retention of viable hybridomas in a
      continuous suspension bioreactor.
AB  - The continuous separation of nonviable hybridoma cells from viable hybridoma
      cells by using a narrow rectangular channel that is inclined from the vertical
      has been investigated experimentally. The effectiveness of the settler in
      selectively retaining viable hybridomas in the bioreactor while permitting the
      removal of nonviable hybridomas has been shown to depend on the flow rate through
      the settler. Intermediate flow rates through the settler have been found to
      provide the highest removal of nonviable hybridomas relative to viable hybridoma
      retention. At high dilution rates through the chemostat, over 95% of the viable
      cells could be partitioned to the bottom of the settler while over 50% of the
      nonviable cells are removed through the top of the settler. This successful
      separation is due to the significantly larger size of the viable hybridomas than
      the nonviable ones. A continuous perfusion experiment was performed in which an
      external inclined settler was used to retain virtually all of the viable
      hybridomas in the culture, while selectively removing from the culture
      approximately 20% of the nonviable cells that entered the settler. A stable
      viable cell concentration of 1.0 x 10(7) cells/mL was achieved, as was an
      antibody productivity of over 50 micrograms/(mL.day). These represent 3- and 6
      fold increases, respectively, over the values obtained from a chemostat culture
      without cell retention.

PMID- 1366837
TI  - Modification of enzyme activity in reversed micelles through clathrate hydrate
      formation.
AB  - The physical phenomenon of clathrate hydrate formation in protein-containing
      reversed micelles is described. Hydrate formation in reversed micelles is a
      method of adjusting the water to surfactant molar ratio, wo, which influences
      micellar size. Lipase and alpha-chymotrypsin encapsulated in large reversed
      micelles of high wo show significant enhancements in activity when the micelle
      size is reduced through hydrate formation. Alternate methods of micelle size
      adjustments also show enhancements in activity. The implications for improving
      the activity of such encapsulated enzymes recovered from fermentation media
      through phase transfer into reversed micelles are discussed.

PMID- 1366839
TI  - Theoretical evaluation of capillary electrophoresis performance.
AB  - An analytical model (Datta and Kotamarthi, 1990) for the electrokinetic
      dispersion coefficient in capillary electrophoresis (CE), for the case of low
      zeta-potential, that accounts for the effects of pressure-driven and/or
      electroosmotic flow of the elutant, is utilized here to theoretically explore the
      performance of CE in terms of plate height, plate number, peak resolution,
      resolving power, and the time of analysis. Practical operating conditions for the
      voltage gradient and Poiseuille flow fraction, v, are explored that optimize CE
      column performance. The implications of the results in the rational design of CE
      columns are discussed. It is also shown that the superposition of Poiseuille flow
      on the natural electroosmotic flow, while allowing greater freedom in the choice
      of elutant velocity, does not always cause increased dispersion.

PMID- 1366838
TI  - Peptide hydrophobicity and partitioning in poly(ethylene glycol)/magnesium
      sulfate aqueous two-phase systems.
AB  - Several amino acids and peptides were partitioned in poly(ethylene glycol)
      (PEG)/magnesium sulfate (MgSO4) aqueous two-phase systems. The partition
      coefficients measured for amino acids and peptides were proportional to the
      difference in PEG concentration between the phases. The partitioning data were
      used to calculate the relative hydrophobicities of individual amino acids, which
      were then used to estimate the hydrophobicities of peptides. The partition
      coefficients of several dipeptides were predicted from these estimated
      hydrophobicities. A series of peptide fragments that compose the pentapeptide
      leucine enkephalin was also partitioned in the PEG/MgSO4 system. Again, the
      partitioning depended upon the hydrophobicities of the individual exposed amino
      acids.

PMID- 1366840
TI  - Fractionation of recombinant tumor necrosis factor using hydrophobic and
      hydrophilic membranes.
AB  - Recombinant tumor necrosis factor (TNF) is expressed in Escherichia coli as a
      soluble intracellular protein. A purification process is described that
      incorporates a hydrophilic membrane (cellulosic) separation followed by a
      hydrophobic one (PTFE). The hydrophilic step is a traditional one in that species
      are separated primarily on the basis of size. The hydrophobic step separates
      species on the basis of parameters apparently not related to size. By combining
      these two steps, an increase in TNF purity of 7-10-fold can be achieved with a
      yield of 50%. The effects of cellular debris and pH on selectivity and recovery
      of the hydrophobic filtration step are discussed.

PMID- 1366841
TI  - Intact chemoreceptor-based biosensors.
AB  - A receptrode biosensor is presented that uses intact chemoreceptor-based
      molecular recognition from antennular structures of the Hawaiian swimming crab
      species Portunis sanguinolentus. The sensor is coupled to a learning, pattern
      recognition calculation for performing analytical chemistry. Action potential
      waveforms are used to establish the identity of individual action potential types
      that can be associated to particular analytes. The pattern recognition
      calculations used are referred to as cluster analysis (CA) and principal
      component analysis (PCA). Action potential similarities are determined by using a
      dendrogram plot of the cluster analysis results and further elucidated by using
      principal component scores plots. Quantitative analysis was performed after
      classification of analyte and background responses. Chemoresponses to salinity
      and trimethylamine N-oxide, two chemical constituents that are found in the
      crustacean living environment, were investigated and gave analytic responses over
      several orders of magnitude.

PMID- 1366842
TI  - Slit scanning of Saccharomyces cerevisiae cells: quantification of asymmetric
      cell division and cell cycle progression in asynchronous culture.
AB  - Slit scanning flow cytometry has been applied to the analysis of the cell cycle
      and cell-cycle-dependent events in Saccharomyces cerevisiae, yielding information
      on the low-resolution spatial distribution of cellular components in single cells
      of unperturbed cell populations. Because this process is rapid, large numbers of
      cells can be analyzed to give distributions of parameters in a given population.
      To study asymmetric cell division and cell cycle progression, forward-angle light
      scattering (FALS) signals together with fluorescence signals from acriflavine
      stained nuclei have been measured in cells from exponentially growing yeast
      populations. An algorithm has been developed that assigns the position of the bud
      neck in the FALS signals so that both FALS and DNA signals can be analyzed in
      terms of the contributions from the mother cell and the cell bud. The data
      indicate that mother cell FALS, on average, remains constant while FALS due to
      the cell bud increases as a cell progresses through the cell cycle. By
      identifying mitotic cells and measuring their properties, we have found that the
      coefficient of variation for the distribution of FALS is smallest within the
      dividing cell population and largest within the newborn cell population, in
      accordance with the critical size control mechanism of yeast cell growth. The use
      of this experimental approach to provide data for statistical population models
      is discussed.

PMID- 1366843
TI  - Quantitation of cell area on glass and fibronectin-coated surfaces by digital
      image analysis.
AB  - By using digital image processing and analysis, two procedures were developed to
      rapidly measure the projected area of a field of adherent 3T3 fibroblasts without
      staining of cell borders. The cell area of newly attached and rounded cells with
      well-resolved borders was obtained by a gray value thresholding procedure. For
      cells that had undergone an appreciable degree of spreading, cell boundaries were
      less distinct and a nonlinear spatial Sobel filter was used, followed by
      thresholding. For both procedures, linear relations were observed between cell
      areas obtained from image analysis and cell areas obtained by tracing. The areas
      of a population of traced cells were not statistically different from the area
      distribution obtained by using the standard curves for the processed images.
      Uncertainty in the estimated mean area depended only upon the number of cells
      examined. Approximate numbers of cells required to obtain estimates of the mean
      are calculated. As an application of these procedures, cell areas were measured
      for 3T3 cells attached to glass and fibronectin-coated surfaces and were found to
      be significantly larger for cells spreading on fibronectin-coated glass than on
      glass alone. Increased cell area during spreading on fibronectin-coated surfaces
      was proportional to increased cell adhesivity after exposure to a shear stress of
      58 dyn/cm2.

PMID- 1366844
TI  - The needs for sensors in bacterial and yeast fermentations.

PMID- 1366845
TI  - Applications of electrochemical sensors.

PMID- 1366846
TI  - Sampling.

PMID- 1366847
TI  - Electrochemical biosensors for bioprocess control.

PMID- 1366848
TI  - Thermistor probes.

PMID- 1366849
TI  - The use of on-line sensors in bioprocess control.
AB  - Commercialization of the products of biotechnology will require a continued
      emphasis on bioprocess design and scale-up. The use of process automation and
      control will help to meet the specifications of quality, safety, and cost. In the
      past, the application of process monitoring and control to biological processes
      has been limited by the availability of suitable sensors. New developments have
      combined the tools of microelectronics and molecular biology to address some of
      these limitations. Continued developments in this area will require close
      cooperation between microbiologists and process engineers to best apply these new
      tools. A general understanding of the concepts of process control, as they relate
      to biological processes, will contribute to that cooperation.

PMID- 1366850
TI  - Multicomponent analysis and chemometrics for bioprocess control.

PMID- 1366851
TI  - On-line monitoring of bioprocesses using HPLC.

PMID- 1366852
TI  - High-performance liquid chromatography.
AB  - Gas chromatography has developed over the past 25 years or so into one of the
      most extensively used on-line analytical techniques in industrial process control
      and optimization. Liquid chromatography, and its several individual techniques,
      is firmly established in the laboratory, but its on-line process use has not
      developed as rapidly as GC. At the present time, only three companies (Applied
      Automation Inc., Dionex Corp., and Millipore Corp.) are active in this area.
      Nevertheless, substantial growth in on-line process LC is predicted for the next
      few years. The techniques of HPLC (normal-phase and reversed-phase), IEC, and SEC
      have great potential in industry as on-line analytical techniques, including the
      new field of biotechnology. Computer-based, multistream, multicomponent systems
      should find extensive use in pilot-plant investigations, where their ability to
      gather large amounts of data (on-line rather than by laboratory testing) could
      have important implications. In bioprocess control, undoubtedly the greatest
      challenge will come in the area of sample-handling technique. On-line
      chromatography has traditionally involved the sampling and conditioning of fairly
      conventional process gases and liquids. One exception is in the plastics and
      elastomers areas, where on-line SEC has been used for polymer MWD measurement.
      Here the sample is more difficult to handle, and some specialized techniques have
      been used. In biotechnology, we are treading new ground; nevertheless, it is
      hoped that some of the experience in sample handling gained in industry over the
      past 25 years will be of use in this new field.

PMID- 1366853
TI  - Applications of NADH-dependent fluorescence sensors for monitoring and
      controlling bioprocesses.

PMID- 1366854
TI  - Fiber-optic sensors in bioprocess control.

PMID- 1366855
TI  - Culture collections as sources of strains for industrial uses.

PMID- 1366856
TI  - Transformation and cloning systems in non-Saccharomyces yeasts.

PMID- 1366857
TI  - Host cell control of heterologous protein production in Saccharomyces cerevisiae.

PMID- 1366858
TI  - A rapid, quantitative microplate assay for NAD-linked D-mannitol dehydrogenase.
AB  - A 96-well microtitre plate assay for NAD-linked D-mannitol dehydrogenase based on
      the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) by reduced NAD is described. The assay allows rapid measurement of D
      mannitol dehydrogenase in crude bacterial extracts derived by sonic disruption,
      in acetone permeabilized cells and in column eluates during enzyme purification.
      The absorbance of reaction mixtures in a microtitre plate is measured at 620 nm
      over a 3-4 min period using a programmable microplate reader. The rate of
      increase in absorbance is directly proportional to the amount of enzyme present
      and there is excellent correlation between activities derived using the
      microplate assay with those determined using conventional spectrophotometric
      methods.

PMID- 1366859
TI  - Cloning and expression of alpha-amylase from Bacillus amyloliquefaciens in a
      stable plasmid vector in Lactobacillus plantarum.
AB  - Lactobacillus plantarum is used in a wide range of agricultural and food
      fermentations. In this paper we report the introduction of alpha-amylase into the
      organism from Bacillus amyloliquefaciens on a stable recombinant plasmid. The
      genetically manipulated organism grew on MRSB medium supplemented with starch and
      it may be a prototype for the development of lactobacilli able to use an
      increased range of substrates in commercial fermentations.

PMID- 1366860
TI  - Characterization and molecular cloning of Bifidobacterium longum cryptic plasmid
      pMB1.
AB  - The small cryptic plasmid pMB1 (1.9 kb), previously isolated from Bifidobacterium
      longum, has been characterized by physical mapping. Two cloning vectors, pMR3 and
      pDG7, carrying chloramphenicol and ampicillin resistances derived from pJH101,
      have been electroporated in Escherichia coli.

PMID- 1366861
TI  - Coiled tube membrane bioreactor for cultivation of hybridoma cells producing
      monoclonal antibodies.
AB  - A coiled tube membrane reactor was developed for the cultivation of mouse-mouse
      hybridoma cells producing monoclonal antibodies. The cell and antibody
      concentrations obtained in the membrane reactor were higher than that obtained in
      a batch spinner flask without a membrane. A mathematical model has been developed
      to describe the membrane transport coupled growth and product formation, and the
      physical and kinetic constants of the system were determined.

PMID- 1366862
TI  - Application of the enzyme thermistor to the direct estimation of intrinsic
      kinetics using the saccharose-immobilized invertase system.
AB  - The possibility of using the enzyme thermistor (ET) for the direct determination
      of kinetic parameters (Km, Ki, Vm) of immobilized enzyme (IME) was evaluated
      using different preparations of invertase conjugated to bead celluloses. Two
      different ET columns packed with IME were operated in the mode of a differential
      enzyme reactor (short length, low substrate conversion). Kinetic parameters of
      the above IME reactor were computed by a nonlinear curve-fitting procedure. The
      obtained kinetic parameters were superverified by means of an independent
      differential reactor (DR) system. This system utilized an indirect postcolumn
      analytical method based on determination of glucose concentration in the stirred
      reservoir. Best agreement between the data acquired by direct (ET) and indirect
      (DR) methods was obtained if the ET column was operated at flow rates within the
      range of 1.0-1.5 ml min-1 using invertase-cellulose chlorotriazine conjugate.
      Influence of heat loss and flow nonideality is discussed. The proposed ET method
      offers a rapid, convenient, and general approach to determination of kinetic
      constants of IME preparations by omitting postcolumn analytical methods.

PMID- 1366863
TI  - Application of carboxypeptidase C for peptide synthesis.
AB  - Carboxypeptidase C partially purified from the flavedo of citrus fruit by a new,
      simple procedure was studied as a catalyst for peptide-bond formation. Dipeptides
      were obtained in high yields (80-95%) with Bz--Tyr--OEt as carboxyl-compound, and
      amino acid amides and amino acid alkylesters as nucleophiles. To characterize the
      synthesis reaction, a number of parameters such as pH, excess of the nucleophile,
      and the molarity of the buffer were evaluated. The yield of dipeptides depends on
      the side chain of the amino acid alkylester used as the carboxyl component as
      well as on the N-terminal protecting group. Esterase activity was minimal in the
      absence of a nucleophile, suggesting a modified mechanism for the synthesis
      reaction compared to other serine proteases. No secondary hydrolysis of the
      peptides formed was observed.

PMID- 1366864
TI  - The production of biotin by recombinant strains of Escherichia coli.

PMID- 1366865
TI  - The genetic engineering approach to beta-lactam antibiotic process strain
      improvement.

PMID- 1366866
TI  - Low-cost microbial detoxification--science or serendipity?

PMID- 1366867
TI  - Optimal feed temperature for an immobilized enzyme packed-bed reactor.
AB  - Optimal feed temperature was determined for a nonisothermal immobilized enzymatic
      reaction with enzyme deactivation in a packed-bed reactor. The optimal feed
      temperature was obtained by maximizing the average substrate conversion over a
      given reaction period. Simulation showed the optimal feed temperature to be
      strongly dependent on the flow dispersion, the reaction activation energy, the
      corresponding enzyme inactivation energy and the heat of reaction. It was also
      observed that in a plug flow reactor the enzyme reaction generally exhibited a
      lower optimal feed temperature and higher substrate conversion than in a
      continuously stirred tank reactor.

PMID- 1366868
TI  - Recycling of salts in partition protein extraction processes.
AB  - Aqueous two-phase extraction systems were developed to separate intracellular
      proteins from cell debris. To economize on the use of chemicals as well as to
      minimize environmental pollution, a closed mode of operation was sought. Various
      approaches to achieve recycling of salt from the primary lower phase containing
      30-60% (w/w) of the added salt together with cell debris, proteins and nucleic
      acids were studied. Techniques assessed included microfiltration, heat treatment
      and the extraction with phase systems formed by aliphatic alcohols. With 20%
      (w/w) primary lower phase it was found to be possible to separate 95% of the salt
      in 3-4 theoretical steps using counter-current extraction.

PMID- 1366869
TI  - Continuous separation of particles from macromolecules in split-flow thin
      (SPLITT) cells.
AB  - A split-flow thin (SPLITT) cell with a perpendicular driving force of one gravity
      has been utilized for the rapid separation of micron-sized particles from
      macromolecules. The procedure involves the simultaneous use of two transport
      mechanisms and thus two operating modes: a sedimentation process controls the
      displacement of the particles across the thickness of the thin channel, while
      diffusion controls the displacement of macromolecules. The theoretical equations
      for these two operating modes are summarized and it is shown how the two modes
      can be combined to yield specified recovery factors. The theory was tested on a
      mixture of 10 microns polystyrene latex beads and three different proteins. The
      observed separation was in excellent agreement with theory. Attempts to
      fractionate red blood cells and plasma proteins from whole blood were only
      partially successful as a consequence of the weak sedimentation of red blood
      cells. Various remedies to this problem are suggested, the most promising of
      which is the use of a SPLITT cell subject to mild centrifugal forces.

PMID- 1366870
TI  - Effects of mutations altering SOS regulation on a nalidixic acid-inducible system
      for the production of heterologous proteins in Escherichia coli.
AB  - The major leftward early promoter of phage lambda pL, has frequently been used to
      drive expression of heterologous genes in Escherichia coli. pL is typically
      maintained fully repressed by the lambda cl protein. When induction of
      heterologous protein synthesis is desired, one of several potential mechanisms of
      destroying cl function is employed and the expression of the foreign gene
      commences. One method of derepressing pL involves exposing cells to nalidixic
      acid, which results in the "activation" of RecA protein and the subsequent RecA
      mediated proteolytic cleavage of cl. Activated RecA also mediates the cleavage of
      the E. coli LexA protein, resulting in induction of the SOS regulon (at least 15
      E. coli genes, including recA). We have examined the effect of two chromosomal
      mutations on the productivity of nalidixic acid inductions. One of the tested
      mutations (recA o) increased the intracellular concentration of RecA prior to
      induction; the other (lexAind-) resulted in a mutated lexA protein insensitive to
      RecA-mediated cleavage. These mutations were introduced into a strain carrying a
      cl+ defective lysogen. Synthesis of two heterologous proteins, human alpha 1
      antitrypsin and a fusion protein partially derived from the Plasmodium falciparum
      circumsporozoite surface antigen, was examined in the wild-type and mutant
      strains. The maximum alpha-1 antitrypsin concentration achieved was improved by
      50% when the recA o strain was used rather than the wild-type; however, only
      smaller changes (20% or less) in the maximum concentration of the malaria fusion
      protein were observed. Use of the lexAind- strain resulted in a decrease in the
      maximum concentration attained for both heterologous products.

PMID- 1366871
TI  - Effect of transcription promoters on the optimal production of secreted protein
      in fed-batch reactors.
AB  - Production of heterologous proteins by yeast secretion imposes additional factors
      that need to be considered, which do not appear with production by direct
      expression. These include additional intracellular polypeptide processing
      dynamics through the secretory organelles and the protein concentration in the
      culture medium, which is the usual final destination of the product. Optimal
      control theory is applied to optimize fed-batch production of secreted protein.
      We maximize an objective function that includes both total production rate and
      product concentration. A mutant invertase is chosen as the model heterologous
      secretory protein. Optimal control control strategies have been obtained for the
      use of two different promoters for the gene transcription, a dere-pressible SUC2
      promoter and a strong glycolytic GPD promoter. With the use of the strong GPD
      promoter, achieving maximum production occurs on the singular arc of maximum
      specific growth rate. As the object switches to maximum product concentration,
      operation occurs for longer periods of time at a slow glucose singular arc
      condition. The optimal control for maximizing protein production with the weak
      SUC2 promoter requires transitions between high and low glucose concentrations
      associated with multiple distinct singular arc conditions. For maximum product
      concentration, the high concentration branches of the singular arc supporting
      maximum growth rate and maximum secretion rate disappear. Operation stays
      essentially on the low glucose concentration branch of the singular arc, which
      maximizes the protein production rate and minimizes the dilution of the broth
      product concentration.

PMID- 1366872
TI  - Defining an optimal carbon source/methionine feed strategy for growth and
      cephalosporin C formation by Cephalosporium acremonium.
AB  - The effect of the method of methionine addition, growth-limiting carbon source
      (glucose vs sucrose), and culture growth rate on cephalosporin C production was
      investigated in a Cephalosporium acremonium defined medium fed batch
      fermentation. Batch addition of methionine, at a concentration of 3 g/L, prior to
      the start of a fed sucrose fermentation was found to interfere with the ability
      of the culture to utilize this sugar, thus limiting growth and decreasing
      cephalosporin C production. Batch methionine addition had no effect on glucose
      limited cultures. Concurrent exponential feeding of methionine with sucrose
      improved both culture growth and productivity. Under the control of identical
      carbon source limiting feed profiles, sucrose was observed to support greater
      cephalosporin C production than glucose. Optimal cephalosporin C production in a
      C. acremonium defined medium fed batch fermentation was obtained through
      controlling culture growth during the rapid growth phase at a relatively low
      level with respect to mumax (mu approximately 0.036 h-1) until achieving a
      desired cell mass with a concurrent sucrose and methionine feed, followed by
      maintaining relatively vigorous growth (mu approximately 0.01 h-1) with sucrose
      for the duration of the fermentation.

PMID- 1366873
TI  - Immobilization of microbial cells in a mixed matrix of silicone polymer and
      calcium alginate gel: epoxidation of 1-octene by Nocardia corallina B-276 in
      organic media.
AB  - Immobilization of Nocardia corallina B-276 was examined for production of 1,2
      epoxyoctane from 1-octene in the presence of n-hexadecane as the organic solvent.
      Hydrophobic silicone polymer was the most suitable material for entrapment of the
      cells. Coentrapment of aqueous reaction medium into the silicone polymer matrix
      improved the epoxide productivity. It was also effective to immobilize the cells
      in a mixed matrix composed of silicone polymer and calcium alginate gel involving
      the reaction medium. In the organic monophase, the amount of epoxide accumulated
      with the cells immobilized in an almost equivolumetric composite of both
      materials was 2 and 7 times the amounts in the silicone and alginate single
      matrices, respectively, and it became larger than with the free cells in the
      aqueous-organic two-liquid phase after a longer period of batch operation. The
      use of such an optimized composite matrix enabled us to perform a relatively
      simple operation of the continuous three-phase bioreactor.

PMID- 1366874
TI  - Fluidized bed adsorption for whole broth extraction.
AB  - Fluidized bed adsorption using a high-density synthetic resin has proven to be an
      invaluable technique for separating novel compounds from unfiltered fermentation
      broths during the very early stages of fermentation development, where product
      concentrations are typically in the parts per million range. Previous initial
      downstream processing strategies consisted of cell separation from whole broth or
      direct extraction with water-immiscible solvents, both of which resulted in
      lengthy time cycles, conflicts with existing operations requiring the use of high
      cost centrifugal separators, and environmental/solvent recovery concerns.
      Laboratory and subsequent pilot plant process development work along with
      concomitant improvements in yield, quality, and time cycles are presented for one
      of several fluidized bed processes piloted in Merck's Natural Product Isolation
      facility.

PMID- 1366876
TI  - Practical considerations in the measurement of culture fluorescence.
AB  - We have examined practical considerations associated with the use of a
      commercially available fluorescence probe for in situ measurements in
      bioreactors. The optical path length of the measurement was first determined and
      a flow cell subsequently designed. The environment (agitation/aeration rates) of
      the probe was found to have a significant influence on the measurement. These
      effects were eliminated by placing the probe in a recycle loop using the flow
      cell. Fluorescence measurement in the recycle loop was verified to be
      representative of the cell sample and to not affect cell metabolism.

PMID- 1366875
TI  - Sparged animal cell bioreactors: mechanism of cell damage and Pluronic F-68
      protection.
AB  - Pluronic F-68 is a widely used protective agent in sparged animal cell
      bioreactors. In this study, the attachment-independent Spodoptera frugiperda Sf9
      insect cell line was used to explore the mechanism of this protective effect and
      the nature of cell damage in sparged bioreactors. First, bubble incorporation via
      cavitation or vortexing was induced by increasing the agitation rate in a surface
      aerated bioreactor; insect cells were rapidly killed under these conditions of
      the absence of polyols. Supplementing the medium with 0.2% (w/v) Pluronic F-68,
      however, fully protected the cells. Next, cell growth was compared in two airlift
      bioreactors with similar geometry but different sparger design; one of these
      bioreactors consisted of a thin membrane distributor, while the other consisted
      of a porous stainless steel distributor. The flow rates and bubble sizes were
      comparable in the two bioreactors. Supplementing the medium with 0.2% (w/v)
      Pluronic F-68 provided full protection to cells growing in the bioreactor with
      the membrane distributor but provided essentially no protection in the bioreactor
      with the stainless steel distributor. These results strongly suggest that cell
      damage can occur in the vicinity of the gas distributor. In addition, these
      results demonstrate that bubble size and gas flow rate are not the only important
      considerations of cell damage in sparged bioreactors. A model of cell death in
      sparged bioreactors is presented.

PMID- 1366877
TI  - Separation processes in biotechnology. Bead mill disruption.

PMID- 1366878
TI  - Enzymatic cell lysis for product release.
AB  - The development of expression systems for recombinant proteins and recombinant
      protein particles which cannot be secreted and are located in specific cell
      locations necessitates the development of novel, more selective techniques for
      cell lysis and or product release. Mechanical cell disruption methods do not
      discriminate the release of the desired product from among a host of other
      contaminating molecules and cell debris, and they may also damage the protein
      product. In contrast, the use of lytic enzyme systems, which can provide
      biological specificity to the process of cell lysis and product release, shows an
      interesting potential for controlled lysis. In this chapter we have reviewed the
      enzymes presently available for cell lysis of bacteria and yeast and have
      described mathematical models developed to describe the process of lysis,
      particularly of yeast cells, including simple, structured, and population balance
      models. Factors affecting the kinetics of lytic enzyme reactions, enzyme
      recovery, and the effect on downstream operations as well as conditions for use
      have been discussed. Sources of lytic enzymes and latest developments on enzyme
      production have been reviewed. Finally, the potential for large-scale use of
      lytic enzyme technology has been discussed. The design and use of lytic enzyme
      systems for differential product release from microbial cells have been reviewed.
      Lytic enzyme systems are usually specific either for yeast or for different types
      of bacteria. The activity profile of a lytic system will have an effect on the
      product distribution. This profile can be manipulated at the genetic,
      physiological, production reactor, enzyme purification, and lysis reactor levels.
      Alternative process designs that will allow the sequential release of products
      from different cell locations are discussed. Alternatives are explored by process
      modeling, process simulation, and optimization techniques. These studies show
      that the use of lytic enzyme systems has tremendous promise as a method of
      controlled lysis and differential product release.

PMID- 1366879
TI  - Chemical, physical, and biochemical concepts in isolation and purification of
      proteins.
AB  - In this chapter the physicochemical basis of protein retention in adsorption
      chromatography has been examined. It is evident from this treatment that
      significant developments are in process with regard to both the theory and
      practice of high-resolution chromatographic methods, particularly at the
      preparative level with adsorptive stationary phases. The recognition that most
      purification strategies must be based on multidimensional multistage procedures
      presents numerous challenges for the protein chemist, the chromatographic
      scientist, and the biochemical engineer. The urgency for these developments has
      been stressed by the potential of modern biotechnology to produce large
      quantities of new proteins that must be obtained in highly purified form. The
      capabilities that these advances present will prove catalytic in the materials
      sciences as new solid phases are examined with particular properties for large
      scale utilization. Similarly, new initiatives in protein engineering will lead to
      greater utilization of the fusion handle approach for selective protein isolation
      and recovery. The realization of these capabilities will represent an
      enthusiastic and innovative method that will revolutionize the role of bioprocess
      development over the next decade.

PMID- 1366881
TI  - Separation processes in biotechnology. Ion-exchange processes.
AB  - Through the use of several differentiating mechanisms, ion exchangers can
      separate ionic and nonionic materials, solutions containing only ionic species,
      and even completely nonionic mixtures. Although the mechanisms are distinct in
      their mode of operation, the resin characteristics that influence the results are
      largely the same. A practical understanding of the resin properties involved is
      all that is necessary to begin to use ion-exchange resins successfully. Ion
      exchange owes most of its history to water treatment, which has provided the
      economic and technological driving force in the past for the development of
      improved resins. However, specialty applications such as those in biotechnology
      are steadily becoming major factors in industry, perhaps not in shear volumes of
      resin used, but certainly in the value added by the process. The field of
      biotechnology no doubt holds many of the exciting new applications for ion
      exchange.

PMID- 1366880
TI  - Chemical permeabilization of cells for intracellular product release.

PMID- 1366882
TI  - Separation processes in biotechnology. Aqueous two-phase separations.
AB  - Aqueous two-phase systems are useful for separation of a wide range of water
      compatible substances (from peptides to cells). The selectivity of the separation
      normally increases with the size of the partitioned molecules or particles. The
      partition and separation capacity can be influenced in a number of ways,
      including electric charge, hydrophobicity, or specific ligand binding. Because of
      the simpleness in operation and high capacity, aqueous two-phase systems are well
      suited for large-scale purification of biomaterials such as enzymes and other
      specific proteins.

PMID- 1366883
TI  - Selection of operations in separation processes.

PMID- 1366884
TI  - Separation processes in biotechnology. Precipitation.
AB  - Precipitation has a clear role in downstream processing for product
      concentration, and ongoing developments promise a more important role in
      fractionation. Its advantages include adaptability to continuous processing and
      larger scales, the wide variety of possible precipitants, and the ability to
      retain biological activity. The focus here has been on precipitation of proteins,
      but many of the principles apply to nucleic acid removal and precipitation of
      lower-molecular-weight biological products, such as pharmaceuticals.

PMID- 1366885
TI  - Ion exchange in purification.
AB  - Biochemicals have large complex three-dimensional structures with multiple weak
      acid and weak base groups on their surfaces. The ionization of these groups
      results in heterogeneous charge structures and complex ion-exchange equilibria.
      In this chapter the ion-exchange equilibria of amino acids are reviewed first.
      The ionization of the alpha-COOH group has a strong effect on the apparent
      equilibrium affinities of amino acids. Salt concentration and pH can also
      significantly affect the apparent affinities and valences. The implications on
      the ion-exchange equilibria of peptides and proteins are discussed. The second
      focus of this chapter is on the local equilibrium models of multicomponent
      chromatographic processes. The differences between unidirectional and two-way
      flow conditions, linear and nonlinear systems, elution and displacement
      processes, and isocratic and gradient operations are discussed. Fundamental
      analysis of these phenomena is applied to formulate strategies to shorten cycle
      time, improve resolution, raise product concentration, and increase throughput.

PMID- 1366886
TI  - Separation processes in biotechnology. Process affinity chromatography.

PMID- 1366887
TI  - Reversed-phase and hydrophobic interaction chromatography of peptides and
      proteins.

PMID- 1366888
TI  - Analysis of effluent profiles in large-scale liquid chromatography.

PMID- 1366889
TI  - Electrically driven separation processes: analytical and preparative methods.

PMID- 1366890
TI  - Automation in protein purification: the use of expert systems for control of
      process chromatography.

PMID- 1366891
TI  - Protein secretion systems in microbial and mammalian cells.
AB  - Secretion is an attractive production mode for proteins that require
      posttranslational modifications carried out in the secretory pathway. For
      example, amino acid chains fold properly, disulfide bonds form correctly, and
      glycosylation occurs accurately as the protein is secreted. In addition, recovery
      of secreted proteins is simplified by the fact that cells need not be broken and
      the product may be a major species present in a minimal synthetic culture medium.
      The current state of the art permits the production and secretion of proteins by
      heterologous cells. While future efforts will be required to improve the
      efficiency of secretion, current methods yield commercially interesting levels of
      secretion from E. coli, B. subtilis, S. cerevisiae, Aspergilli, and many
      mammalian cell types. Each of these systems offers certain advantages, and the
      choice of system depends on the specific protein to be secreted. High-value human
      therapeutic products such as plasminogen activators are reasonable candidates for
      secretion from mammalian cell lines, while industrial proteins such as calf
      prochymosin require a more economical host, such as baker's yeast or Aspergillus.
      The wide variety of posttranslational modifications observed in nature may
      prevent any single secretion system from dominating the field for many years to
      come.

PMID- 1366892
TI  - Cell disruption by homogenizer.

PMID- 1366893
TI  - Separations for biotechnology.

PMID- 1366894
TI  - Altered gene expression in plants due to trans interactions between homologous
      genes.
AB  - We have attempted to explain co-suppression in terms of a hypothesis whereby
      homologous sequences are able to interact somatically in trans, in a manner
      influenced by sequence context or location. We have speculated that there might
      be mechanistic similarities between co-suppression and some other trans
      interaction and epigenetic phenomena in plants, fungi and animals; and that it
      might be the sequence context in which a gene lies, or its location in the genome
      that influences the likelihood that it will participate in these phenomena. We
      suspect that elucidation of the mechanisms behind these phenomena will play a
      role in developing a better understanding of the relationship between nuclear
      architecture and gene expression. This, in turn, will be helpful in understanding
      the developmental regulatory mechanisms that exert control over somatic trans
      interactions in plants, and perhaps in understanding some aspects of the basis of
      cellular differentiation in development.

PMID- 1366895
TI  - Safety in industrial microbiology and biotechnology: UK and European
      classifications of microorganisms and laboratories.

PMID- 1366896
TI  - New approaches to the synthesis of antiviral nucleosides.
AB  - There is a pressing, worldwide need for new antiviral agents. The chemical
      synthesis of novel nucleosides for chemotherapeutic screening usually involves
      multistage processes which can be time consuming. The application of enzymatic
      methods for the synthesis and modification of antiviral nucleosides shows great
      promise because of the simplicity and high specificity of enzymatic reactions.

PMID- 1366897
TI  - European biopharmaceutical culture.

PMID- 1366898
TI  - Transgenics primed for research.

PMID- 1366899
TI  - Brave new biosensors.

PMID- 1366900
TI  - Hen egg white lysozyme expressed in, and secreted from, Aspergillus niger is
      correctly processed and folded.
AB  - We transformed Aspergillus niger with the full length cDNA gene encoding hen egg
      white lysozyme (HEWL) and its secretion signal sequence. Lysozyme levels up to 12
      mg/l were secreted when expression was controlled by the A. awamori glucoamylase
      (GAM) promoter and 1 mg/l when controlled by the A. nidulans glyceraldehyde-3
      phosphate dehydrogenase (GPD) promoter. N-terminal sequence analysis of the
      recombinant protein indicated that the signal peptide was correctly processed by
      the A. niger secretory apparatus. The specific catalytic activity of the
      recombinant protein was identical to that of authentic hen lysozyme. The
      recombinant HEWL was examined by 2D 1H-NMR spectroscopy and shown to have a
      spectrum identical to that of authentic HEWL indicating that the protein was
      correctly folded.

PMID- 1366901
TI  - Applications of imaging spectroscopy in molecular biology. II. Colony screening
      based on absorption spectra.
AB  - Digital imaging spectroscopy has been used to obtain the grayscale spectrum of
      colored bacterial colonies directly from petri dishes. Up to 500 individual
      colony spectra can be simultaneously recorded and processed from a single plate.
      Spectra can be obtained in the visible to near infrared region (400nm-900nm) with
      10nm resolution. Instrument response is normalized through run-time radiometric
      calibration such that each grayscale spectrum can be converted to the ground
      state absorption spectrum of the colony. In this study, mutants of the
      photosynthetic bacterium Rhodobacter capsulatus have been differentiated by the
      absorption spectra of their pigment-protein complexes. This imaging technique is
      applicable to chromogenic systems in which colony and/or media color (e.g.
      indicator plates) provides a quantitative indicator of gene expression.

PMID- 1366902
TI  - Controlled release of interleukin-2 from biodegradable microspheres.
AB  - We have evaluated the use of biodegradable poly(DL-lactide-co-glycolide)
      microspheres for the controlled release of interleukin-2 (IL-2) and its modified
      forms: succinyl IL-2 (SIL-2) and polyethylene glycol-modified IL-2 (PEG IL-2). We
      show that a microsphere formulation can be prepared from PEG IL-2 using HSA as an
      excipient which, after an initial burst, releases 2-3% PEG IL-2 per day in a
      bioactive form continuously over a 20- to 30-day period.

PMID- 1366903
TI  - Inverse polymerase chain reaction.

PMID- 1366904
TI  - Errata. Genotyping of bovine kappa-casein following DNA sequence amplification.

PMID- 1366905
TI  - Protease-catalyzed synthetic reactions and immobilization-activation of the
      enzymes in hydrophilic organic solvents.
AB  - The catalytic feature of serine proteases for synthetic reactions in hydrophilic
      organic solvents and effects of immobilization by complexation with
      polysaccharides are described. Free alpha-chymotrypsin and subtilisin Carlsberg
      catalyze esterification, transesterification, and peptide synthesis in hydro
      organic cosolvents with less than 10% water. Subtilisin BPN' is catalytically
      less active. The medium effects on the reaction kinetics and product yield were
      investigated in terms of the nature of solvent and water content in the reaction
      systems. The substrate- and stereo-specificities of the enzymes suggest that the
      enzymes maintain their native conformations in these low-water organic solvents.
      The catalytic activities of the proteases markedly increase by immobilization or
      complexation with polysaccharides, such as chitin or chitosan. The results of the
      rate measurements suggest that the primary role of the support materials is the
      activation of the enzymes and the increase in substrate concentration at reaction
      sites.

PMID- 1366906
TI  - Immobilization of genetically engineered cells: a new strategy for higher
      stability.
AB  - The r-DNA clones improve the bioprocess and provide better economics, if and when
      properly developed. In recent times, many approaches were made to improve the
      stability of recombinants in a reactor which includes both genetic and
      environmental methods, but many of them were proved to be unsuccessful in the
      scale-up process. The immobilization technique, exploited recently for the
      cultivation of recombinants, in many cases gave high cell concentrations, better
      expression of cloned gene products and also maintained plasmid stability for
      longer periods in a host under continuous operation in comparison to a free cell
      system. Many plasmids and hosts were tested for improved stabilities. So far, no
      explanation was provided for higher stability in the immobilized system. However,
      it was observed to reduce the competition between the plasmid harboring and
      plasmid free cells in a matrix. The stability of recombinant strains under
      immobilization technique is affected by various factors, and these are important
      parameters for the commercial process. Thus, the immobilization system is
      promising for the successful cultivation and scale-up of genetically engineered
      cells.

PMID- 1366908
TI  - Enzymatic synthesis of polyaniline film using a copper-containing oxidoreductase:
      bilirubin oxidase.
AB  - Electroactive polyaniline films have been synthesized by using a copper
      containing oxidoreductase, bilirubin oxidase (BOD). Enzymatic polymerization took
      place on the surface of BOD-adsorbed solid matrix which was in contact with a
      buffer solution containing aniline. Optimum conditions for enzymatic
      polymerization of aniline were investigated. Elemental analysis and IR
      spectroscopy indicated that the enzymatically synthesized film was polyaniline.
      The cyclic voltammetric studies demonstrated that the polyaniline film was
      electrochemically reversible in the redox properties in acidic aqueous solutions.
      Since the film retained enzymatic activity of BOD which was employed as a
      catalyst for polymerization, enzymatic polymerization seems promising in
      preparation of immobilized enzyme membranes.

PMID- 1366907
TI  - Recombinant brewer's yeast strains suitable for accelerated brewing.
AB  - Four brewer's yeast strains carrying the alpha-ald gene of Klebsiella terrigena
      (ex. Aerobacter aerogenes) or of Enterobacter aerogenes on autonomously
      replicating plasmids were constructed. The alpha-ald genes were linked either to
      the ADC1 promoter or to the PGK1 promoter of yeast Saccharomyces cerevisiae. In
      pilot scale brewing (50 l) with three of these recombinant yeasts the formation
      of diacetyl in beer was so low during fermentation that lagering was not
      required. All other brewing properties of the strains were unaffected and the
      quality of finished beers was as good as that of finished beer prepared with the
      control strain. The total process time of beer production could therefore be
      reduced to 2 weeks, in contrast to about 5 weeks required in the conventional
      process.

PMID- 1366909
TI  - Electrical effects on the proliferation of living HeLa cells cultured on
      optically transparent electrode surface.
AB  - Low d.c. potential application induced changes of cellular morphology and growth
      of living cells on a potential-controlled electrode. At a potential range higher
      than +0.7 V (vs. Ag/AgCl), serious electric effects on cell viability, membrane
      permeability, and cytoskeletal morphology of HeLa cells were observed. On the
      other hand, at lower than +0.5 V no effect was observed. At the boundary
      potential range between +0.5 V to +0.7 V, where HeLa cells were cultured on the
      potential-controlled optically transparent In2O3 electrode (OTE) surface,
      intriguing effects on HeLa cells appeared. At this potential range, where HeLa
      cells cultured on a potential-applied OTE, all the cells were alive accompanying
      morphological change. The morphology of HeLa cells returned to their normal
      spindle shape, when potential application to the electrode was cut off. At a
      potential of +0.65 V, cell proliferation ratio of cultured cell on an electrode
      was about one-fifth of that on a non-controlled electrode. These results suggest
      that low d.c. electrical effects induce significant change in cellular morphology
      and function.

PMID- 1366911
TI  - Production of L-tryptophan from D,L-5-indolylmethylhydantoin by resting cells of
      a mutant of Arthrobacter species (DSM 3747).
AB  - The reaction parameters and the stereospecificity of the enzymatic cleavage of
      D,L-5-indolylmethylhydantoin in producing L-tryptophan with resting cells of
      Arthrobacter sp. DSM 3747 were studied. When intact cells were tested, the
      optimal pH was between 8.5 and 9.0 and the optimal temperature was 50 degrees C.
      Both, L-N-carbamoylase and hydantoinase could be stabilized over 24 h at 30 and
      40 degrees C by the addition of D,L-5-indolylmethylhydantoin. Furthermore, the
      hydantoinase was stable over 24 h at 50 degrees C by the addition of 0.5 mM Mn2+
      ions. The treatment with sodium desoxycholate turned out to be successful in
      overcoming the poor availability of D,L-5-indolylmethylhydantoin for the cells.
      The optimal temperature with permeabilized cells decreased to 30 degrees C and
      therefore ensured a good enzyme stability. While the L-N-carbamoylase proved to
      be absolutely L-specific, the hydantoinase led to a mixture of enantiomers of N
      carbamoyltryptophan. The produced D-N-carbamoyl-tryptophan caused an inhibition
      of the L-N-carbamoylase. The transformation yield from D,L-5
      indolylmethylhydantoin always reached 100%.

PMID- 1366910
TI  - Cell growth and enzyme synthesis of a mutant of Arthrobacter sp. (DSM 3747) used
      for the production of L-amino acids from D,L-5-monosubstituted hydantoins.
AB  - A microorganism with the ability to form L-tryptophan from D,L-5-(3-indolyl
      methyl)hydantoin (D,L-5-IMH) was isolated and identified as Arthrobacter sp. (DSM
      3747). After isolation of a mutant with high tryptophan production activity but
      low tryptophan degradation, cultural conditions were optimized to achieve high
      amounts of biomass with good specific activities concerning the enzymatic
      hydantoin-cleaving reactions. The ability of the microorganism to perform these
      bioconversions was found to be inducible by D,L-5-IMH as well as to be dependent
      on the presence of Mn2+. The highest specific D,L-5-IMH-cleaving activity of the
      cells was observed in the exponential phase of growth. The addition of yeast
      extract to the mineral salts medium was found to be essential for obtaining
      biomass concentrations of about 25 g l-1 cell dry mass by bioreactor
      cultivations. In order to obtain a constantly high growth rate, feeding of the C
      source was pO2-controlled. The inducer D,L-5-IMH had to be continuously fed to
      prevent a decline of the L-tryptophan-forming enzyme activities, because it was
      subjected to degradation with the enzymes induced and higher concentrations of
      D,L-5-IMH aggravated the growth significantly. The synthesis of the enzymes was
      also inducible, when inducer and Mn2+ were not added until the late growth phase.
      Using this process, the consumption of D,L-5-IMH was reduced remarkably. So,
      under these conditions biomass concentrations of 25 g l-1 cell dry weight with a
      specific enzymatic activity of 0.20 mmol g-1 h-1 (tryptophan per dry mass per
      time) could be obtained within 13 h. Using 1 g l-1 of the chemically modified
      inducer D,L-5-(3-indolylmethyl)-3-N-methylhydantoin, which was not degradable by
      the microorganisms, a biomass concentration of 28 g l-1 cell dry weight with a
      specific activity of 0.34 mmol g-1 h-1 (tryptophan per dry mass per time) could
      be obtained within 28 h.

PMID- 1366912
TI  - Production of recombinant human interleukin-2 with BHK cells in a hollow fibre
      and a stirred tank reactor with protein-free medium.
AB  - For the production of recombinant human interleukin-2 (IL-2) two different
      culture processes, a 1-2 liter homogeneous stirred bubble-free aerated system and
      a dense cell hollow fibre bioreactor were compared. Cultivations were carried out
      with serum- or protein-free medium formulations. In the stirred culture 0.75 mg
      IL-2 were produced with 1 l of perfused medium at a maximum cell number of 3 X
      10(10). The product yield in the hollow fibre module was only 0.23 mg l-1 at a
      maximum cell number of 6 X 10(10). In contrast to results with hybridoma or EBV
      transformed cell lines, in which hollow fibre bioreactors showed comparable
      efficiency to perfused stirred tank reactors, the tissue-like cell density is
      disadvantageous as adherent cells tend to stick together leaving insufficient
      intercellular space for removal of product.

PMID- 1366913
TI  - A yeast system for stable expression of hepatitis B surface antigen.
AB  - We have constructed a yeast strain that has integrated into its chromosomal
      ribosomal RNA gene site two copies of Hepatitis B virus surface (HBS) antigen
      gene under the control of the yeast (Saccharomyces cerevisiae) glyceraldehyde-3
      phosphate dehydrogenase (GAP) promoter and terminator. The level of expression of
      HBS gene was low in the strain, but upon chemical and physical mutageneses, in
      combination with an immunological screening procedure, a mutant clone which
      expressed HBS protein at a high level was obtained. This mutant strain produces
      HBS antigen stably under non-selective conditions.

PMID- 1366914
TI  - Differential stability of recombinant human insulin-like growth factor II in
      Escherichia coli and Staphylococcus aureus.
AB  - Recombinant human insulin-like growth factor II (IGF-II), produced as a soluble
      extracellular fusion protein, was shown to be proteolytically degraded in
      Escherichia coli. In contrast, the fusion protein secreted from Staphylococcus
      aureus was stable and the full length product could be recovered by affinity
      chromatography. After site specific cleavage of the fusion protein, soluble IGF
      II with biological activity was obtained without refolding procedures. These
      results demonstrate that a eukaryotic protein unstable in E. coli can be
      stabilized by expression in a Gram positive host. The full-length fusion protein
      from S. aureus was used to characterize the protease responsible for the
      degradation in E. coli. Biochemical and genetic analysis suggests a specific
      degradation by the outer membrane protease (OmpT).

PMID- 1366915
TI  - Liver alcohol dehydrogenase immobilized on polyvinylidene difluoride.
AB  - A physical method for immobilization of liver alcohol dehydrogenase (ADH) by
      hydrophobic adsorption onto a supporting membrane of polyvinylidene difluoride
      (PVDF) was performed. Simultaneously, a physicochemical characterization of the
      immobilized enzyme regarding its kinetic behaviour was performed. The activity/pH
      profile observed points to an effect of pH on activity that is completely
      different from the case of ADH in solution. The disturbance in the typical bell
      shaped profile owing to the fact that the enzyme was immobilized is explained on
      the basis of a potent limitation to the diffusion of the protons in the support.
      The findings of the present work also reveal the existence of an effect that
      limits free external diffusion of the substrate towards and/or the product from
      the support; this effect seems to be the determinant of the overall rate of the
      enzymatic reaction and is thus of great importance in the effective kinetic
      behaviour (v([S])) of immobilized ADH, whose kinetic behaviour is complex (non
      Michaelian), as may be seen from the lack of linearity observed in the
      corresponding double reciprocal and Eadie-Hofstee plots. By non-linear regression
      numerical analysis of the v([S]) data and application of the F-test for model
      discrimination, the minimum rate equation necessary to describe the intrinsic
      kinetic behaviour of PVDF-immobilized ADH proved to be one of the polynomial
      quotient type of degree 2:2 (in substrate concentration).

PMID- 1366916
TI  - Recent advances in the design of anion-selective membrane electrodes.

PMID- 1366917
TI  - Capillary electrophoresis of small molecule pharmaceuticals.

PMID- 1366918
TI  - Microwave hydrolysis of peptides and proteins for amino acid analysis.
AB  - The speed, accuracy, and convenience of microwave hydrolysis make it a promising
      new technique in the protein chemistry field. Acid hydrolysis of protein samples
      has traditionally been the rate limiting step in amino acid analysis. Complete
      hydrolysis and analysis of proteins and synthetic peptides is now possible in
      less than an hour using microwave hydrolysis. This represents a significant
      improvement in quality control monitoring capability during the synthesis of high
      purity peptides. Microwave hydrolysis will also facilitate basic research in
      molecular biology and streamline sample preparation procedures for amino acid
      assays in the food science area.

PMID- 1366919
TI  - New instrument for quantitative electrophoresis.

PMID- 1366920
TI  - CP-82,996, a novel diglycoside polyether antibiotic related to monensin and
      produced by Actinomadura sp.
AB  - A new polyether antibiotic CP-82,996 (C50H86O16) was isolated by solvent
      extraction from the fermentation broth of Actinomadura sp. (ATCC 53764).
      Following purification by silica gel column chromatography and crystallization,
      the structure of CP-82,996 was determined by a single crystal X-ray analysis. The
      structure is closely related to monensin, but is unique in that it contains two
      sugar groups, whereas monensin has none. The 1H and 13C NMR chemical shifts and
      assignments for CP-82,996 were elucidated, and they were compared with those
      determined previously for monensin. CP-82,996 is active against certain Gram
      positive bacteria, and is a very potent anticoccidial agent. It effectively
      controlled chicken coccidiosis caused by several Eimeria species at 5-10 ppm in
      feed, and is 10-20 times more potent than monensin.

PMID- 1366921
TI  - Protein fusions: bioseparation and application.

PMID- 1366922
TI  - Extending the chemistry of enzymes and abzymes.
AB  - Selective chemical modification can be used to create novel proteins,
      particularly enzymes and antibodies, with altered specificities and catalytic
      activities in vitro. Modification strategies now being developed should soon
      yield a wide spectrum of novel biomolecules whose activities are optimized for
      specific industrial processes or therapeutic applications.

PMID- 1366923
TI  - Towards an understanding of the genetics of bacterial metal resistance.
AB  - Many bacteria show great promise for use in metal recovery. However, the genetics
      of metal-leaching, accumulation-resistance, and oxidation/reduction mechanisms of
      these bacteria is still an area of research in its infancy. The introduction of
      such genes into bacteria of economic importance would have application in
      biomining and environmental bioremediation.

PMID- 1366924
TI  - New attempts to solve protein structures lead to MADness.

PMID- 1366925
TI  - The proof of the cloning is in the eating.

PMID- 1366926
TI  - Progress towards rabies control.
AB  - Although safe and efficacious tissue-culture-derived rabies vaccines are
      available in developed countries, much of the world still depends on vaccines
      derived from neural tissue which were introduced half a century ago. Considerable
      advances have been made in our understanding of the molecular biology of rabies
      virus, and genetically engineered recombinant viruses (vaccinia-rabies virus
      glycoprotein) have been developed. These may facilitate the control of rabies in
      some species by oral vaccination campaigns.

PMID- 1366927
TI  - The advent of recombinant pertussis vaccines.

PMID- 1366928
TI  - A modern vaccine for an ancient plague: rinderpest.

PMID- 1366929
TI  - Gene replacement in Bordetella pertussis by transformation with linear DNA.
AB  - We replaced the wild-type TOX operon of Bordetella pertussis with in vitro
      mutated, detoxified alleles by electroporetic transformation using unmarked
      linear DNA. Uptake of DNA was selected by transient ampicillin resistance and two
      simultaneous recombination events resulted in gene-replacement at the natural
      locus with no integration of heterologous DNA. TOX alleles were stable without
      selection and recombinant strains secreted non-toxic, fully assembled, protective
      pertussis toxin (PT) analogues with kinetics similar to the parental vaccine
      strain under production-scale fermentation conditions. Strains generated in this
      way are suitable for the production of recombinant whole-cell or component
      whooping cough vaccines that require no chemical modification of PT.

PMID- 1366930
TI  - Protective surface antigen P69 of Bordetella pertussis: its characterization and
      very high level expression in Escherichia coli.
AB  - The surface antigen, P69 of Bordetella pertussis, an N-terminal fragment of the
      precursor protein, P93, is likely to be an important component of future subunit
      vaccines against whooping cough. We have expressed several defined N-terminal
      fragments of P93 in E. coli and compared their electrophoretic mobilities with
      that of purified P69 from B. pertussis. These experiments show that P69 is
      considerably smaller than the 69 kD originally estimated from its gel mobility
      and is probably 60.4 kD in size. Our initial plasmids expressed only very low
      levels of this antigen. We diagnosed the limiting factor to be a poor ribosome
      binding site (RBS) by demonstrating a large stimulation of expression on a two
      cistron plasmid. The limitation of expression could be completely overcome by
      only two base changes close to the initiation codon, resulting in a further
      increase in expression of P69 at levels to 30-40% total cell protein. Although
      the protein accumulated as insoluble inclusion bodies, it could be solubilized by
      guanidinium chloride.

PMID- 1366931
TI  - High-level direct expression of semi-synthetic human interleukin-6 in Escherichia
      coli and production of N-terminus met-free product.
AB  - We have developed a direct expression system for high-level production of
      recombinant human interleukin-6 (rhIL-6) in Escherichia coli. In this system, (i)
      the natural N-terminal coding region of the hIL-6 gene was replaced by a
      synthetic sequence containing A-T rich codons, (ii) dual Shine-Dalgarno (SD)
      sequences were employed, (iii) an A-T rich segment was inserted in front of the
      initiation codon to avoid putative mRNA secondary structure in the region and
      (iv) the natural amber termination codon of the hIL-6 gene was changed to an
      ocher stop codon. The hIL-6 polypeptide, synthesized at a high level, formed
      cytoplasmic inclusion bodies. After refolding, the N-terminal methionine was
      removed by aminopeptidase-P in vitro. The purified recombinant hIL-6 had B-cell
      differentiation activity equivalent to natural IL-6 from a human T-cell culture.

PMID- 1366932
TI  - New sequence scanners come of age.

PMID- 1366933
TI  - States noticing field releases.

PMID- 1366934
TI  - Transgenic farm animals.

PMID- 1366935
TI  - Immobilized and free cell continuous cultures of a recombinant E. coli producing
      catechol 2,3-dioxygenase in a two-stage chemostat: improvement of plasmid
      stability.
AB  - The immobilization of recombinant strains of E. coli W3110/pTG205 in K
      carrageenan gel beads improves the plasmid stability during continuous cultures
      in the absence of selection pressure. Since, xyl E gene (which encodes catechol
      2,3-dioxygenase from Pseudomonas putida) transcription is controlled by the trp
      promoter, the effects of tryptophan (repressor) and 3 beta-indolyl acrylic acid
      (derepressor) on pTG 205 stability and enzyme production have been studied in
      both free and immobilized cell cultures. A two-stage continuous culture system
      running for 150 h is described. In the first stage an immobilized culture is
      performed in the presence of tryptophan with a significant plasmid stability. The
      cells released from the gel beads are continuously transferred in the second
      stage reactor where expression is induced by 3 beta-indolyl acrylic acid. In
      these conditions an efficient production of catechol 2,3-dioxygenase is observed.

PMID- 1366937
TI  - Growth kinetics of Chinese hamster ovary cells in a compact loop bioreactor. 3.
      Selection and characterization of an anchorage-independent subline and medium
      improvement.
AB  - Four sublines of Chinese hamster ovary (CHO) cells were selected or cloned on a
      10% fetal calf serum supplemented MEM-alpha medium. Three of them were monolayer
      cultures and could proliferate by 2000 times a week (mu = 1.1 d 1) in T-flasks.
      The other subline, S1, could grow in suspension even in static T-flask cultures.
      The stability in chromosome number of these cell lines was investigated. By
      evaluating the kinetic growth parameters, i.e. the specific rates of growth,
      glucose consumption and lactic acid production, and the yields of cells and
      lactic acid from glucose, the S1 cells were considered to be the most suitable
      subline for the bioreactor suspension culture. The S1 cells reached the greatest
      maximum of cell concentration among all cell lines tested because of their
      efficient glucose utilization. Observed nutrient limitations in the S1 cell
      culture was overcome by modification of the medium composition, that is addition
      of 10 mg l-1 hypoxanthine, 1 mg l-1 FeSO4.7H2O, and 0.1 mg l-1 sodium putrescine,
      elimination of glutamine, supplementation of 6 mM asparagine and double amount of
      isoleucine, leucine, methionine and vitamins other than ascorbic acid,
      cyanocobalamin and biotin, increase of NaHCO3 concentration from 26 to 40 mM, and
      finally decrease of NaCl concentration from 122 to 100 mM. With this modified
      medium, 7.2 X 10(6) ml-1 of the maximum cell concentration was observed in a
      glucose fed-batch culture, the cell concentration which was twice as much as in
      batch cultures with the original medium.

PMID- 1366936
TI  - Selective adherence of neurons and glial cells from dissociated cerebral and
      spinal cord microcarrier cultures.
AB  - In stationary cultures of dissociated brain and spinal cord grown on
      microcarriers (MCs), the neuronal and ependymal cells attached to the MCs forming
      floating aggregates in which they grow in a three-dimensional pattern. The glial
      and meningeal elements on the contrary, tend to dissociate from the aggregates
      and adhere to the plastic dish where they divide to form a monolayer. This
      different behavior of CNS components is not observed in rotating cultures in
      which all CNS cells remain attached to the MCs and develop into mature floating
      structures. This cell separation in stationary MC-cultures which is documented
      here by SEM and immunocytochemistry, may be useful for analysis and evaluation of
      the metabolic biochemical events of each of the cellular components derived from
      the same culture.

PMID- 1366938
TI  - Effect of initial cell density on hybridoma growth, metabolism, and monoclonal
      antibody production.
AB  - A murine hybridoma cell line (167.4G5.3) was cultivated in batch mode with
      varying inoculum cell densities using IMDM media of varying fetal bovine serum
      concentrations. It was observed that maximum cell concentrations as well as the
      amount of monoclonal antibody attainable in batch mode were dependent on the
      inoculum size. Specifically, cultures with lower inoculum size resulted in lower
      cell yield and lower antibody concentrations. However, in the range of 10(2) to
      10(5) cells per ml, the initial cell density affected the initial growth rate by
      a factor of only 20%. Furthermore, specific monoclonal antibody production rates
      were independent of initial cell density and the serum concentration. Glutamine
      was the limiting nutrient for all the cultures, determining the extent of growth
      and the amount of antibody produced. Serum was essential for cell growth and
      cultures with initial cell concentrations up to 10(6) cells per ml could not grow
      without serum. However, when adapted, the cells could grow in a custom-made serum
      free medium containing insulin, transferrin, ethanolamine, and selenium (ITES)
      supplements. The cells adapted to the ITES medium could grow with an initial
      growth rate slightly higher than in 1.25% serum and the growth rate showed an
      initial density dependency-inocula at 10(3) cells per ml grew 30% slower than
      those at 10(4) or 10(5). This difference in growth rate was decreased to 10% with
      the addition of conditioned ITES medium. The addition of conditioned media,
      however, did not improve the cell growth for serum-containing batches.

PMID- 1366939
TI  - Two stage cultures for the production of berberine in cell suspension cultures of
      Thalictrum rugosum.
AB  - Two stage culture systems were examined in cell suspensions of Thalictrum rugosum
      which produce berberine in a growth associated manner. The utilization of indole
      3-acetic acid (IAA) as a growth regulator, in place of 2,4-dichlorophenoxyacetic
      acid (2,4-D), at various growth phases was investigated. Although the enhancing
      effect was clear when it was used separately, in combination with 2,4-D effect of
      IAA was suppressed and medium change from 2,4-D to IAA was detrimental to product
      formation. The decrease of berberine production in this two stage culture may be
      due to the loss of conditioning factors associated with medium replacement.

PMID- 1366940
TI  - Purification of the glycoprotein allergen Ag7 from mugwort pollen by concanavalin
      A affinity chromatography.
AB  - Two affinity columns comprising immobilized concanavalin A (Con A), Con A
      Sepharose and Con A-XP3507, were evaluated for their purifying ability for the
      glycoprotein allergen Ag7 from a partially purified extract of mugwort pollen.
      The most pronounced difference between the two columns was the nature of their
      nonspecific interactions; hydrophobic interactions were dominant with Con A
      XP3507, whereas ionic interactions were dominant with Con A-Sepharose. Both Con A
      columns were effective for purifying Ag7 with a recovery of 50% after specific
      elution with displacing sugars. The inclusion of 1.0 M NaCl and 20% ethylene
      glycol in the elution medium was useful for desorbing nonspecifically bound
      material, prior to specific elution of adsorbed Ag7 in the presence of the
      displacing sugars, alpha-methyl glucoside and alpha-methyl mannoside. The most
      efficient purification of Ag7 was achieved with Con A-Sepharose at room
      temperature rather than at 4 degrees C. Affinity chromatography with Con A-XP3507
      resulted in a slightly more contaminated product (purity 54%) than with Con A
      Sepharose (purity 64%).

PMID- 1366941
TI  - Measurement of oxygen concentration gradients in gel-immobilized recombinant
      Escherichia coli.
AB  - In this study, an oxygen microsensor was used to measure oxygen concentration
      profiles in carrageenan gel particles containing growing, immobilized Escherichia
      coli B (pTG201). Profiles, which were measured at intervals during continuous
      culture of gel slabs and beads, became increasingly steep with time. The oxygen
      penetration depth in the gel decreased with time, eventually reaching a steady
      state value of approximately 100 microns for both gel beads and slabs. A reaction
      diffusion model employing zero-order cell growth kinetics was found to provide an
      excellent fit to the experimental concentration data. Growth rates estimated from
      profiles obtained during the first few hours of culture were 0.24h-1 (gel slabs)
      and 0.18h-1 (beads), compared to a value of 0.30 h-1 measured in free-cell
      suspensions at 25 degrees C.

PMID- 1366943
TI  - Properties and repeated use of a reversibly soluble-insoluble yeast lytic enzyme.
AB  - A yeast lytic enzyme was covalently immobilized on an enteric coating polymer,
      Eudragit S, that is reversibly soluble and insoluble (S-IS) depending on the pH
      of the reaction medium. The yeast lytic enzyme immobilized on Eudragit S (Y-E)
      showed a sharp response of solubility to slight changes in pH without decrease in
      enzymatic activity. The specific activity per amount of enzyme protein of Y-E for
      dry yeast cells was about two-thirds that of the native enzyme. In both lysis
      reactions of dry and pressed baker's yeast cells, changing the pH of the reaction
      medium from 7.0 to 4.8 at an appropriate interval allows the insoluble Y-E and
      the reaction products (soluble protein for dry yeast cells and invertase and
      soluble protein for pressed baker's yeast cells) to be repeatedly separated. The
      reaction method using a reversible S-IS enzyme is a promising procedure for
      repeated use of the enzyme in a heterogeneous reaction system containing yeast
      cells as a substrate.

PMID- 1366942
TI  - Effect of free-cell growth parameters on oxygen concentration profiles in gel
      immobilized recombinant Escherichia coli.
AB  - Oxygen concentration profiles in immobilized recombinant cells were measured
      using a microsensor. Experimental results showed that the final depth of oxygen
      penetration in the carrageenan gel was always in the range 80-100 microns for the
      strains and media used, although profiles of oxygen concentration during the
      early stages of cell growth depended on the strain and nutrient medium used.
      Variations in the oxygen profiles corresponded to differences in kinetic
      parameters measured for the same strains and media in free-cell experiments.

PMID- 1366944
TI  - Cloning of a gene coding for phosphotransacetylase from Escherichia coli.
AB  - A phosphotransacetylase gene (pta) has been cloned from a genomic DNA library of
      Escherichia coli 1100, a derivative of strain K-12. The phosphotransacetylase
      activities of pta+ plasmid-containing strains were amplified about 150-fold under
      control of the lac promoter. The molecular weight of the phosphotransacetylase
      was estimated to be about 81,000 by sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis. The pta gene was found to be downstream of ackA by a combination
      of restriction analysis and plasmid subcloning. It is located about 13 kb
      upstream of the purF-folC-hisT region of the chromosome.

PMID- 1366946
TI  - A large-format 2-D electrophoresis system for routine laboratory use.

PMID- 1366945
TI  - Practical methods for preservation of cultured cells by freezing.

PMID- 1366947
TI  - Low IgG fetal bovine serum.

PMID- 1366948
TI  - High performance thermal cycling.

PMID- 1366949
TI  - Catalytic antibodies--something for everyone.

PMID- 1366950
TI  - Reconstituted viral envelopes--'Trojan horses' for drug delivery and gene
      therapy?
AB  - Reconstituted viral envelopes (RVEs) are formed by solubilizing intact virus in
      detergent and reassembling the envelope on removal of detergent. RVEs can be
      formed in the presence of agents that become encapsulated and can then be
      utilized in vitro and in vivo for drug delivery, cell destruction, transfer of
      membrane components, and as vectors for genetic engineering. The problems with
      biotechnological applications of RVEs and possible strategies for overcoming them
      are discussed in this article.

PMID- 1366951
TI  - The twists and turns of biopolymer migration.

PMID- 1366952
TI  - Exponential amplification of nucleic acids: new diagnostics using DNA polymerases
      and RNA replicases.
AB  - Recent developments in DNA and RNA amplification technology are enabling the
      design of ultra-sensitive diagnostic assays for infectious diseases. The leading
      amplification technology is the polymerase chain reaction (PCR). An alternative
      approach, Q-beta amplification, also promises remarkable speed and precise
      quantification of assay results.

PMID- 1366954
TI  - Codifying common sense.

PMID- 1366953
TI  - Repacking protein interiors.
AB  - Several goals of protein engineering may be achieved through redesign and
      repacking of protein interiors. The effects of interior apolar substitutions on
      protein stability depend strongly on the site of the substitution. One reason for
      this is that protein interiors have properties both of apolar liquids and of
      crystalline solids. Substitutions at interior sites affect the stability of a
      protein by changing the hydrophobicity, but each site in a protein has a
      characteristic energy associated with introducing packing changes, and the net
      stability depends on both of these factors.

PMID- 1366955
TI  - New tricks for an old workhorse.

PMID- 1366956
TI  - Protein design: rules, empiricism, & nature.

PMID- 1366957
TI  - Toward using in vitro toxicology in the drug approval process.

PMID- 1366958
TI  - Alternative routes through the genome.

PMID- 1366959
TI  - Vision assisted robotics and tape technology in the life-science laboratory:
      applications to genome analysis.
AB  - Recent proposals to analyze a number of major genomes have created a need for
      methods of rapidly manipulating and assaying very large numbers of specimens
      containing DNA fragments. Systems for sampling semi-solid biological material
      from mixed disordered arrays are required. These samples need to be sorted in an
      ordered format and stored in minimum space at known locations. It should be
      possible to recall them quickly from stock, individually or collectively, for
      duplication or re-ordering into new arrays for appropriate analysis. This article
      reviews a range of problems associated with high speed multiple specimen handling
      and assay in the molecular biology laboratory and outlines the solutions
      currently available to address these difficulties. Designs for automatic systems
      to manipulate biosamples and analyze DNA are presented.

PMID- 1366960
TI  - A novel, quantitative bioassay for type I interferon using a recombinant
      indicator cell line.
AB  - We describe a specific and quantitative novel assay for biologically active human
      type I interferon (IFN), the MxR assay. It is based on a Vero cell line
      containing multiple copies of a hybrid gene consisting of the murine Mx promoter,
      which is responsive to type I IFN, linked to the human growth hormone (hGH)
      transcription unit. Exposure of this cell line to IFN-alpha or -beta for 12-48
      hours results in the production of hGH that is measured by a commercially
      available radio-immune assay. The response to IFN-alpha is dose-dependent between
      3 and 1000 units/ml. There is no response to TNF, IL-1 and a number of other
      cytokines and growth factors, and only a negligible response to IFN-gamma.

PMID- 1366961
TI  - Development of expression vectors for transgenic fish.
AB  - Genetic alteration of fish is important for aquatic biotechnology as well as for
      investigating molecular interactions that occur during vertebrate development.
      The numerous, large, transparent, and externally fertilized eggs of many fish
      species make them ideally suitable for genetic manipulation, especially for
      production of transgenic animals. Genetic engineering of fish requires suitable
      expression vectors. Accordingly, we developed two fish expression vectors, FV-1
      and FV-2, which contain the proximal promoter and enhancer regulatory elements of
      the carp beta-actin gene and the polyadenylation signal from the salmon growth
      hormone gene. The two fish expression vectors were tested in microinjected fish
      eggs and in tissue cultured fish and mammalian cells. These two "all-fish"
      expression vectors should be useful for genetic engineering of fish and have been
      used with growth-enhancing genes in transgenic fish.

PMID- 1366962
TI  - A nuclear magnetic resonance technique for determining hybridoma cell
      concentration in hollow fiber bioreactors.
AB  - We have developed a technique for determining cell concentration in a hollow
      fiber bioreactor based on 23Na nuclear magnetic resonance (NMR) spectroscopy.
      Cell concentrations determined with this method agreed closely with
      concentrations calculated from 31P NMR nucleoside triphosphate (NTP) measurements
      and oxygen consumption rate measurements. Oxygen transfer limitations, which can
      complicate cell mass determinations based on oxygen consumption rates, were shown
      to be negligible for the bioreactor used. Specific antibody production rates in
      hollow fiber culture, calculated from these cell number estimates, were similar
      to those found in suspension culture for this cell line.

PMID- 1366964
TI  - British Coordinating Committee for Biotechnology.

PMID- 1366963
TI  - Rehydratable gels: a potential reference standard support for electrophoresing
      PCR-amplified DNA.

PMID- 1366965
TI  - Biosorption of radionuclides by fungal biomass.
AB  - Four kinds of bioreactor were evaluated for thorium removal by fungal biomass.
      Static-bed or stirred-bed bioreactors did not give satisfactory thorium removal
      probably because of poor mixing. An air-lift bioreactor removed approximately 90
      95% of the thorium supplied over extended time periods and exhibited a well
      defined breakthrough point after biosorbent saturation. The air-lift bioreactor
      promoted efficient circulation and effective contact between the thorium solution
      and the mycelial pellets. Of several fungal species tested, Rhizopus arrhizus and
      Aspergillus niger were the most effective biosorbents with loading capacities of
      0.5 and 0.6 mmol g-1 respectively (116 and 138 mg g-1) at an inflow thorium
      concentration of 3 mmol dm-3. The efficiency of thorium biosorption by A. niger
      was markedly reduced in the presence of other inorganic solutes while thorium
      biosorption by R. arrhizus was relatively unaffected. Air-lift bioreactors
      containing R. arrhizus biomass could effectively remove thorium from acidic
      solution (1 mol dm-3 HNO3) over a wide range of initial thorium concentrations
      (0.1-3 mmol dm-3). The biotechnological application and significance of these
      results are discussed in the wider context of fungal biosorption of
      radionuclides.

PMID- 1366966
TI  - Recovery of metal ions by microfungal filters.
AB  - Many microfungi contain chitin/chitosan as an integral part of the cell wall
      structure. The binding of toxic and heavy metal ions by chitosan or partly
      deacetylated chitin is a direct consequence of the base strength of the primary
      amine group and is most effective for those metals that form complexes with
      ammonia. Of the microfungi studied, hyphae from Mucor mucedo and Rhizomucor
      miehei, after treatment with hydroxide to expose the chitin/chitosan, were found
      to be most effective in the capture of metal ions. Chemically treated mycelia
      have so far been shown to bind silver, zinc, lead, copper, nickel, cobalt,
      cadmium, iron and chromium, with the efficiency of metal-ion binding apparently
      being inversely proportional to the valency state of the metal ions to be bound.
      Wet-laid papers produced from mixed slurries of treated mycelia and various
      conventional paper-making and textile fibres have exceptionally good tensile- and
      bursting-strength properties, particularly in the wet state. Papers containing 1
      g treated mycelia removed up to 90% of various metal ions in solution (50 cm3,
      1.5 mmol dm-3) with flow rates of 0.5 cm3 cm-2 min-1. However, the total metal
      ion binding capacities of single-thickness microfungal papers are limited under
      constant flow conditions. The total volume flowing through the system before
      metal-ion breakthrough occurs increases in direct proportion to the number of
      sheets of microfungal paper but the concomitant reduction in flow rates becomes a
      limiting factor. Mycelia-containing structures that allow efficient metal-ion
      binding at commercially acceptable flow rates are currently being investigated.

PMID- 1366967
TI  - An immobilized cell bioprocess for the removal of heavy metals from aqueous
      flows.
AB  - Microorganisms can be used to remove toxic heavy metals from liquid industrial
      wastes. In addition to the chemical toxicity of many of the latter, the
      production of long-lived nuclides from nuclear power programmes has introduced
      additional radiotoxicological hazards. Associated problems of the presence of
      contaminating, non-metal co-pollutants and the presentation of dilute, high
      volume wastes have received little attention. Traditional biotechnological waste
      treatments have relied either on the use of non-living biomass ('biosorption') or
      on the accumulation of metals by living cells with the associated problems of
      metal toxicity effects and the requirements for cell viability or growth.
      Identification of an enzymically-mediated metal accumulation step can permit
      decoupling of cell growth from metal accumulation. Using pre-grown biomass
      immobilized in a flow-through filter ('bioreactor') the metal-accumulative
      bioprocess can be described accurately applying traditional Michaelis-Menten
      kinetics. The effect of co-pollutants can be then quantified in order to run the
      bioreactor in the most efficient way.

PMID- 1366968
TI  - Review of biotechnology applications to nuclear waste treatment.
AB  - This paper gives an overview of the feasibility of the application of
      biotechnology to nuclear waste treatment. The contents are based on a report
      which PA Technology carried out for the Department of the Environment (DoE
      Reference: DoE/RW/88.008 Sector No 2.3). Many living and dead organisms
      accumulate heavy metals and radionuclides. The controlled use of this phenomenon
      forms the basis for the application of biotechnology to the removal of
      radionuclides from nuclear waste streams. Indeed, biotechnology offers a series
      of new opportunities for removal of radionuclides from dilute aqueous process
      effluents. Such technology is already used for heavy metal removal on a
      commercial basis and could be optimised for radionuclide removal. An overview of
      biotechnology areas, namely the use of biopolymers and biosorption using biomass
      applicable to the removal of radionuclides from industrial nuclear effluents is
      given. The potential of biomagnetic separation technology, genetic engineering
      and monoclonal antibody technology is also to be examined. The most appropriate
      technologies to develop for radionuclide removal in the short term appear to be
      those based on biosorption of radionuclides by biomass and the use of modified
      and unmodified biopolymers in the medium term.

PMID- 1366969
TI  - Metal recovery using chitosan.
AB  - Chitosan is a natural polycationic polymer which possesses valuable properties as
      a metal recovering and water purifying agent. Applications are waste water
      treatment for heavy metal and radio isotope removal and valuable metal recovery,
      potable water purification for reduction of unwanted metals, agriculture-
      controlled release of trace metals essential to plant growth, food--complex
      binding of iron in precooked food to reduce 'warmed-over flavour'. The
      interactions of metals with chitosan are complex, probably simultaneously
      dominated by adsorption, ion-exchange and chelation. To study this it is of
      utmost importance to work with well characterized chitosans. This has been a
      problem as available characterizing methodology is limited. Degree of
      polymerization and deacetylation and the distribution of acetyl groups along the
      polymer chain is of crucial importance for chitosan metal interacting
      characteristics. Making chemical derivatives is a way to alter the metal
      interacting characteristics of chitosan. Chitosan possesses general
      coagulant/flocculant characteristics towards bio-molecules and surfaces.

PMID- 1366970
TI  - Effects of oxygen supply on the production of nikkomycin with immobilized cells
      of Streptomyces tendae.
AB  - For continuous production of the antibiotic nikkomycin immobilized cells have
      been used in a fluidized bed bioreactor. Cells of Streptomyces tendae were
      immobilized on sintered glass particles. Different biomass concentrations on the
      particles correspond to different thicknesses of mycelial layers because growth
      occurs only on the outer surface of the particles. The antibiotic productivity
      decreased with increasing layer thickness. In fermentations with higher
      concentrations of both biomass on the particles and dissolved oxygen levels of
      about 70% the productivity was also limited because of limited oxygen diffusion
      in the layers.

PMID- 1366971
TI  - Coupled reductive and oxidative degradation of 4-chloro-2-nitrophenol by a co
      immobilized mixed culture system.
AB  - The restriction of oxygen transfer in Ca-alginate beads used for the
      immobilization of microbial cells was applied to a coupled reductive and
      oxidative microbial degradation of the xenobiotic 4-chloro-2-nitrophenol (CNP).
      The conversion of CNP by Enterobacter cloacae under anaerobic conditions led to
      the formation of 4-chloro-2-aminophenol (CAP, 81%) and 4-chloro-2-acetaminophenol
      (CAAP, 16%) after 50 h incubation. CAP, the main reduction product, was further
      degraded under aerobic conditions by Alcaligenes sp. TK-2, a hybrid strain
      isolated by conjugative in-vivo gene transfer. Whereas both degradation steps
      excluded one another in homogeneous systems with free cells, a coupled reductive
      and oxidative degradation of CNP was observed in one aerated reactor system after
      co-immobilization of both strains in Ca alginate. The diameter of the alginate
      beads used for immobilization was recognized as one main factor determining the
      properties of this mixed culture system.

PMID- 1366972
TI  - Quantification and identification of the main components of the Trichoderma
      cellulase complex with monoclonal antibodies using an enzyme-linked immunosorbent
      assay (ELISA).
AB  - An enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies has been
      developed to measure the concentration of three main cellulase components from
      Trichoderma reesei, cellobiohydrolase I (CBH I), cellobiohydrolase II (CBH II)
      and endoglucanase I (EG I), in both commercial enzyme preparations as well as in
      samples from laboratory fermentations. The sensitivity of the assay is 1-10 ng
      protein, depending on the type of cellulase. The coefficient of variability is
      between 10% and 20%. By a combination of two different domain-specific
      monoclonals against CBH I or II it is also possible to quantify the concentration
      of intact and truncated forms of these two enzymes, respectively. The use of the
      ELISA to quantify the formation of the three cellulase components under different
      cultivation conditions is described.

PMID- 1366973
TI  - Aryl acylamidase from Rhodococcus erythropolis NCIB 12273.
AB  - A Rhodococcus erythropolis strain was isolated from soil on the basis of its
      ability to use acetaminophen as the sole source of both carbon and energy for
      growth. When grown in a complex medium containing an anilide inducer compound,
      the bacterium exhibited aryl acylamidase (EC 3.5.1.13) activity. This activity
      was not subject to carbon or nitrogen repression by the growth medium
      constituents as the enzyme was present throughout the exponential growth phase.
      The anilide was converted to the corresponding aniline, which was not further
      degraded. The enzyme was partially purified by a variety of methods including a
      batch ion exchange procedure, column ion exchange chromatography and hydrophobic
      interaction chromatography. The enzyme had a maximum activity at around pH 8.0
      and had a Km for acetaminophen of 0.11 mM. Electrochemical assays of aryl
      acylamidase activity are described. The enzyme is suitable for use as a reagent
      in the clinical diagnostic measurement of acetaminophen.

PMID- 1366974
TI  - Improved transformation frequency and heterologous promoter recognition in
      Aspergillus niger.
AB  - Wild-type strains of Aspergillus niger were transformed with integrative vectors.
      The number of stable transformants varied from approximately 20-30/micrograms up
      to 17,000/micrograms using acetamide and hygromycin B selection, respectively.
      The introduction of deletions of 5' and 3' non-coding regions of the acetamidase
      gene (amdS+) revealed that these sequences influenced the number of
      transformants. The molecular characterization of A. niger transformants revealed
      that several copies of the vectors were tandemly integrated into the nuclear DNA.
      These oligomers were stably inherited, even after 100 days of growth on non
      selective medium. The expression of the vector-encoded genes was confirmed by
      evidence from the mRNAs and corresponding proteins encoded by the selectable
      marker genes.

PMID- 1366976
TI  - Peptide and amino acid transport in Streptococcus bovis.
AB  - In amino acid transport studies with Streptococcus bovis using 14C-labelled amino
      acids, it has been shown that between 87% and 95% of cell-associated
      radioactivity was located in the cytosol. In similar studies with unlabelled
      peptides, most test peptide associated with S. bovis was truly intracellular.
      Using sodium dodecyl sulphate-polyacrylamide gel electrophoresis, the proteolytic
      activity in S. bovis was found to be largely cell-associated and of the serine
      protease type, but stimulated by dithiothreitol. A wide range of extracellular
      peptide hydrolysing activities was demonstrated against the pentapeptide Leu-Trp
      Met-Arg-Phe, which was completely hydrolysed to eight products after 10 min
      incubation. Some of this pentapeptide was transported intact, indicating the
      existence of mechanisms for the transport of peptides up to 751 Da. In studies
      with Arg-Phe-Ala, only Phe (F) and Ala (A), and to a much lesser extent Phe-Ala
      (FA) were transported after extracellular hydrolysis to FA, Arg (R), F and A. In
      this case, amino acid transport was much more predominant than peptide transport.
      The extent and nature of peptide transport was affected by the addition of
      protease inhibitors.

PMID- 1366975
TI  - High cell density fermentation of recombinant Escherichia coli expressing human
      interferon alpha 1.
AB  - A defined medium was developed which, by means of a specific fed-batch mode,
      allows growth of the recombinant Escherichia coli strain TG1 (pBB210) up to a
      cell density of 60 g dry weight/l. Apart from glucose and aqueous ammonia fed as
      carbon and nitrogen sources, it was necessary to supply other nutrients or O2
      enriched air. Aqueous ammonia also served for pH control. The pO2 level was kept
      at 20% saturation via closed-loop controls operating the two output variables of
      stirrer speed and glucose feeding rate. This fed-batch method prevented
      significant accumulation of acetate and other metabolic by-products. The
      recombinant E. coli expressed interferon alpha 1 more efficiently at a lower
      specific growth rate (muPr approximately 0.15 h-1) than at the maximum specific
      growth rate (mu max = 0.45 h-1). Therefore, fermentation in the batch phase at mu
      max was only allowed to continue up to a medium cell density. In the succeeding
      fed-batch phase, the specific growth rate was reduced to muPr by increasing the
      stirrer speed according to an empirically developed time scale.

PMID- 1366977
TI  - Influence of medium exchange schedules on metabolic, growth, and GM-CSF secretion
      rates of genetically engineered NIH-3T3 cells.
AB  - The metabolic and secretory characteristics of NIH-3T3 fibroblasts transfected
      with a cDNA encoding human granulocyte-macrophage colony stimulating factor (GM
      CSF) were examined as a function of the culture medium exchange schedule. The
      rates of glucose and glutamine consumption and of lactate and ammonia production
      were measured over exchange schedules ranging from complete medium replacement
      weekly (1/week) to complete medium replacement daily (7/week). All measured
      metabolic rates increased with increased medium exchange rates and accelerated
      sharply between exchange rates of 3.5/week and 7/week. The lactate/glucose and
      ammonia/glutamine yield coefficients, however, remained invariant at about 1.9
      and 1.0 mol/mol, respectively, under all medium perfusion conditions. A shift-up
      in medium perfusion rates from 3.5/week to 7/week resulted in increased metabolic
      rates that resembled those observed in the cultures that were exchanged at the
      7/week rate throughout, showing that the metabolic rates could be directly
      controlled by the perfusion rate. Differential regulation of medium versus serum
      perfusion demonstrated that increased NIH-3T3 cell metabolism was directly
      proportional to the serum flux to which the cells were exposed. Thus a limiting
      serum component is responsible for the altered metabolic and growth rates. The GM
      CSF production by the transfected 3T3 cells was stable but exhibited substantial
      transient increases during periods of cell proliferation, demonstrating that the
      secretion of transfected gene products can be highly modulated even when the cDNA
      is driven from a constitutive promoter. These studies show that the metabolic and
      secretory behavior of genetically engineered cells is influenced by the medium
      exchange schedule.

PMID- 1366979
TI  - Rapid immunoassay technique for process monitoring of animal cell fermentations.
AB  - A calibration and quality control technique suited to process monitoring with
      immunoassay is demonstrated. The particle concentration fluorescence immunoassay
      (PC-FIA) is shown to provide a sensitive and rapid method for the quantification
      of specific biomolecules in cell cultures. Smoothing of linear calibration
      parameters is performed by forming weighted averages of standard points as the
      run progresses. These estimates are then used to determine slope and intercept
      values for improved calibration. The nonuniformity of the fluorescent signal
      variance is also considered, and a weight model is developed to describe the
      relationship between signal fluorescence and signal variance for weighted linear
      curve fitting. Pooling calibration results over the process run improves overall
      assay performance as determined by using standard control chart analysis. This
      method is suitable for semicontinuous monitoring of animal cell fermentations and
      has been used here to measure cell-associated and culture supernatant
      concentrations of monoclonal antibody (Ab) from hybridoma cells. The cell
      associated Ab concentration correlates with cell-specific production rate. Assay
      times on the order of 10 min for supernatant and 25-30 min for cell-associated Ab
      concentrations can be achieved, making this procedure suitable for process
      monitoring and control. Under these conditions the assay has a detection limit of
      approximately 10 ng/mL, providing a sensitive and specific method for the
      quantification of cell culture constituents.

PMID- 1366978
TI  - Monitoring cell concentration and activity by multiple excitation fluorometry.
AB  - Four key cellular metabolic fluorophores--tryptophan, pyridoxine, NAD(P)H, and
      riboflavin--were monitored on-line by a multiple excitation fluorometric system
      (MEFS) and a modified SLM 8000C scanning spectrofluorometer in three model yeast
      fermentation systems--bakers' yeast growing on glucose, Candida utilis growing on
      ethanol, and Saccharomyces cerevisiae RTY110/pRB58 growing on glucose. The
      measured fluorescence signals were compared with cell concentration, protein
      concentration, and cellular activity. The results indicate that the behavior and
      fluorescence intensity of various fluorophores differ in the various fermentation
      systems. Tryptophan fluorescence is the best signal for the monitoring of cell
      concentration in bakers' yeast and C. utilis fermentations. Pyridoxine fluoresce
      is the best signal for the monitoring of cell concentration in the S. cerevisiae
      RTY110/pRB58 fermentation. In bakers' yeast fermentations the pyridoxine
      fluorescence signal can be used to monitor cellular activity. The NAD(P)H
      fluorescence signal is a good indicator of cellular activity in the C. utilis
      fermentation. For this fermentation NAD(P)H fluorescence can be used to control
      ethanol feeding in a fed-batch process.

PMID- 1366980
TI  - Strategies for the recovery of chemicals from fermentation: a review of the use
      of polymeric adsorbents.
AB  - Many different compounds can be produced by using microorganisms or enzymes. An
      important element in the design of a viable biotechnological process is the
      selection of an economical and efficient separations train. Production of
      chemicals via biotechnology generally requires isolation and purification from
      dilute, aqueous solution. A general framework for separation process design
      relies on exploiting a unique molecular physicochemical property (or properties)
      for separating the molecule of interest from water and the other species in
      solution. Important properties that can be utilized for the recovery of low
      molecular weight polar compounds are molecular charge, hydrophobicity, Lewis
      acidity or basicity, volatility, and limited solubility. In turn, it can be
      useful to characterize molecular properties by using separation processes, such
      as, for example, hydrophobicity by measuring octanol/water partition
      coefficients. This paper reviews the use of adsorption onto hydrophobic, nonpolar
      macroreticular polymers and Lewis acid-base complexation by using functionalized
      polymers for the recovery of amino acids, carboxylic acids, alcohols, and ketones
      from dilute aqueous solution. The focus will be on utilizing physical and
      chemical properties to predict uptake capacity. This information will be relevant
      to separation process development and will help to characterize molecular
      properties in aqueous solution.

PMID- 1366981
TI  - Application of population balance model to the loss of hybridoma antibody
      productivity.
AB  - A simple dynamic model has been applied to explain the population dynamics of
      monoclonal antibody (MAb) producing (producer) and nonproducing hybridoma cells
      (nonproducer) coexisting in culture. The events of mutation or loss of genes
      associated with antibody synthesis have been incorporated into the model to
      account for the conversion of a producer to a nonproducer. The model shows that
      the cell population is not necessarily dominated by the nonproducer, and a steady
      balance of producer and nonproducer populations can be achieved. A nonproducer
      population is undesirable, and cultivation strategies to maximize MAb production
      are suggested, taking into account the dynamics of a nonproducer population.

PMID- 1366982
TI  - High-level secretion of human apolipoprotein E produced in Escherichia coli: use
      of a secretion plasmid containing tandemly polymerized ompF-hybrid gene.
AB  - A gene encoding the mature form of human apolipoprotein E (h-apoE) was fused to
      the secretion signal coding sequence of the Escherichia coli major outer membrane
      protein F (ompF) which was preceded by a consensus Shine-Dalgarno sequence. Two
      copies of this hybrid gene were inserted tandemly into an expression vector and
      expressed in E. coli under the transcriptional control of two tac promoters
      regulated by lac repressors. By the addition of isopropyl-beta-D
      thiogalactopyranoside (IPTG) to the growth media, cells synthesized h-apoE at the
      level of 27.2 micrograms per A600 and up to 22% of the total cellular protein.
      The h-apoE produced by E. coli was processed precisely, secreted into the
      periplasmic space and formed protein aggregates there. However, despite
      aggregation, they were easily dissolved in water and actively formed protein
      lipid complexes with dimyristoyl phosphatidyl choline (DMPC). These results
      demonstrated that E. coli cells are able to synthesize and secrete a large amount
      of active h-apoE using a prokaryotic signal sequence.

PMID- 1366983
TI  - Pilot scale production of a Trichoderma reesei endo-beta-glucanase by brewer's
      yeast.
AB  - Endo-beta-glucanase I (EGI) of Trichoderma reesei was produced in laboratory and
      pilot scale using recombinant strains of "bottom-fermenting" Saccharomyces
      cerevisiae. The gene eg/1 was integrated in the chromosome or an expression
      cassette was inserted on a multicopy plasmid. Expression levels were compared in
      a laboratory scale bioreactor. The best EGI-producing strain was cultivated in
      pilot scale. Adsorbent treatment was used to remove endogenous yeast proteins and
      other impurities from the culture filtrate during concentration. Effective pilot
      scale one-step purification of the EGI protein was obtained using DEAE-Sepharose,
      on which EGI was weakly bound. The purified enzyme reacted with antibodies
      prepared against T. reesei EGI and catalyzed the hydrolysis of both insoluble and
      soluble substrates.

PMID- 1366984
TI  - Effect of free fatty acids and phospholipids on growth of and product formation
      by recombinant baby hamster kidney (rBHK) and Chinese hamster ovary (rCHO) cells
      in culture.
AB  - Recombinant BHK and CHO cells producing human antithrombin III (rh ATIII) were
      used to investigate the utilization of phospholipids and free fatty acids from
      low-serum (0.1% FBS) culture medium. Both cell lines show distinctly different
      patterns of fatty acid utilization. For rBHK ATIII cells it is shown that under
      low serum conditions several different combinations of free fatty acids (bound to
      bovine albumin) elicit an identical growth stimulatory effect although individual
      consumption and production rates of fatty acids are different. Increased fatty
      acid concentrations lead to increased uptake rates without any further effect on
      growth rate being observed. Recombinant antithrombin III formation is found to be
      a function of combinations and concentrations of fatty acids present in the
      culture medium.

PMID- 1366985
TI  - Macroreticulate buffers: a novel approach to pH control in living systems.
AB  - It is possible to control the pH of growing living systems in vitro by adding, to
      the growth media, macroreticulate buffers, i.e. amphoteric resins made with
      buffering and titrant groups simultaneously affixed to the matrix. Such beads
      possess a very precise isoelectric point (pI) and are able to maintain the
      solutions' pH close to their pI values for extended growth periods. These pearls
      are made of a neutral polyacrylamide backbone containing up to 200 mM grafted
      weak acrylamido acids and bases. It is possible to produce such buffers with any
      desired pH value in the pH 2.5-11 scale. An example is given of conditioning the
      pH of endive plants grown hydroponically.

PMID- 1366987
TI  - The effect of pH on the production of pertussis toxin by Bordetella pertussis.
AB  - The production of pertussis toxin by Bordetella pertussis was increased by
      controlling the pH at 7.0 through the addition of sulfuric acid. The more
      commonly used hydrochloric acid and Tris buffer were observed to be detrimental
      to toxin yields.

PMID- 1366986
TI  - Cloning of three endoglucanase genes from Thermomonospora curvata into
      Escherichia coli.
AB  - A BamHI genomic library from Thermomonospora curvata was constructed in E. coli
      using cosmid vector pHC79. Four clones able to hydrolyze CMC were isolated.
      Restriction digests and Southern gel analysis revealed the presence of three
      different endoglucanase genes. DNA fragments contained in all of the
      endoglucanase cosmids hybridized to T. curvata chromosomal DNA. The cellulase
      genes were expressed in E. coli, but at rather low levels.

PMID- 1366988
TI  - Terminology--a plea for consistency.

PMID- 1366989
TI  - High cell density suspension culture of mammalian anchorage independent cells:
      oxygen transfer by gas sparging and defoaming with a hydrophobic net.
AB  - Gas sparging directly into the culture-broth is not done in cell culture, except
      when the gas flow rate is very small, because much foaming occurs. During
      screening of defoaming methods, foam was observed to be broken up effectively
      when it made contact with a net fabricated from hydrophobic materials. Providing
      a highly efficient oxygen supply to suspension culture was tried using the new
      defoaming method. In a 5 l reactor equipped with the foam-eliminating net
      fabricated with polysiloxane, oxygen was transferred at 21 mmole/l.h equivalent
      to a consumption rate of 1 X 10(8) cells/ml, even at a low oxygen gas flow rate
      of 0.1 cm/s corresponding to a fourth of the gas flow rate when foam leaked
      through the net. Perfusion culture of rat ascites hepatoma cell JTC-1 was
      successfully carried out in the 5 l scale culture system with the net and a
      hydrophobic membrane for cell filtration. The viable cell concentration reached
      2.7 X 10(7) cells/ml after twenty-seven days, in spite of the nutrient-deficient
      condition of the lower medium exchange rate, that is, a working volume a day, and
      viability was maintained at more than 90%. In a 1.21 scale culture of mouse-mouse
      hybridoma cell STK-1, viable cell concentration reached 4 X 10(7) cells/ml. These
      results showed that oxygen transfer by gas sparging with defoaming was useful for
      high density suspension culture. A foam-breaking mechanism was proposed.

PMID- 1366990
TI  - Regulation and expression of transforming growth factor type-beta during early
      mammalian development.
AB  - We have examined the effect of differentiation on the expression of different
      members of the transforming growth factor type-beta (TGF-beta) family using
      embryonal carcinoma (EC) cells and early mammalian embryos. We determined that
      TGF-beta activity increases approximately 25-100% when the mouse EC cell line,
      F9, is induced to differentiate with retinoic acid (RA). Interestingly, the
      increased TGF-beta activity reflects the induction of TGF-beta 2 secretion
      following differentiation of both F9 EC cells and the human EC cell line, NT2/D1.
      Using the technique of reverse transcription-polymerase chain reaction (RT-PCR),
      we have verified that differentiation induces the expression of TGF-beta 2 as
      well as a distant member of the TGF-beta family, Vgr-1. Transcripts for TGF-beta
      2 and Vgr-1 were readily detected in the differentiated cells of F9 and PC-13 but
      not in their undifferentiated counterparts. Moreover, TGF-beta 2 mRNA was readily
      detected in NT2/D1 cells following differentiation. In addition, transcripts for
      TGF-beta 2 were detected by RT-PCR in mouse morulae, preimplantation blastocysts
      and cultured blastocysts. Based on the data presented, it appears that the
      expression of both TGF-beta 2 and Vgr-1 is closely associated with the induction
      of differentiation during early development.

PMID- 1366991
TI  - Membrane modifications in the course of hepatocyte isolation.
AB  - A transmission E/M, scanning E/M and freeze fracture ultrastructural study has
      been performed on the rat hepatocyte in the course of isolation from the liver
      parenchyma. The cell submicroscopic aspect indicates a good morpho-functional
      preservation from the liver perfusion to the final stages of cell isolation. The
      freeze fracture membrane analysis evidentiates the constant presence of gap
      junctions and tight junctions, characterized by particular structural
      alterations, probably due to progressive functional uncoupling. The persistence
      of these cell differentiations until complete cell isolation may be considered a
      further morphological expression of the maintenance of the differentiated stage
      of the hepatocyte. Fragments of membranes from adjacent cells, still adherent to
      isolated hepatocyte surfaces, can also be occasionally detected by freeze
      fracture techniques.

PMID- 1366992
TI  - Multistage production of Autographa californica nuclear polyhedrosis virus in
      insect cell cultures.
AB  - The aim of our study was to establish an efficient system for the in vitro
      production of the insect pathogenic Autographa californica nuclear polyhedrosis
      virus in a Spodoptera frugiperda cell line. We optimized cultivation conditions
      for cell proliferation as well as for virus replication in a 1.5 litre stirred
      tank bioreactor. Cell and virus propagation were found to be optimal at a
      constant oxygen tension of 40%. In order to provide sufficient nutrients during
      virus synthesis filtration and perfusion devices were connected to the
      bioreactor. A virus production procedure in a repeated batch mode by using a two
      stage bioreactor system is described. Stage I was optimized for cell production
      and stage II for virus production.

PMID- 1366993
TI  - Antibody production in packed bed reactors using serum-free and protein-free
      medium.
AB  - The present work demonstrates the utility of packed bed reactors for the
      production of monoclonal antibody. We present data from a continuous process run
      for the production of over 100 grams of antibody, using serum-free medium. An
      additional pilot run also demonstrates the potential for continued antibody
      production under protein-free conditions, using a standard basal medium.

PMID- 1366994
TI  - Improved culture conditions for Cowdria ruminantium (Rickettsiales), the agent of
      heartwater disease of domestic ruminants.
AB  - The causal agent of heartwater disease of domestic ruminants, Cowdria
      ruminantium, can, with difficulty, be isolated and passaged in lines of bovine
      endothelial cells grown in the presence of the Glasgow modification of Eagle's
      minimal essential medium. However, when Leibovitz's L-15 medium supplemented with
      0.45% glucose at pH 6.0-6.5 is used as maintenance medium for these cells,
      isolation and serial passage may routinely be achieved.

PMID- 1366995
TI  - Bioconversion of avermectin into 27-OH avermectin.
AB  - The bioconversion of avermectin to its 27-hydroxy derivative is achieved with
      Nocardia autotrophica subsp. canberrica. The approach of increasing bioconversion
      productivity rather than efficiency was adopted in these studies. Process
      improvement studies focused on the physico-chemical conditions of the
      fermentation, examined initially at the shake-flask scale. Bioconversion yields
      were affected by pH, substrate concentration, time of substrate addition,
      substrate solubilization, carbon to nitrogen ratio, and medium strength.
      Optimization of these parameters resulted in a 8-fold process improvement. During
      pre scale-up studies, the sensitivity of this bioconversion to the antifoam
      employed was demonstrated and lard oil was selected as giving the best results.
      Additional process changes were required during scale-up efforts in larger
      vessels, including replacement of the original substrate solvent with
      dimethylsulfoxide.

PMID- 1366996
TI  - DNA sequence analysis of endoglucanase genes from Pseudomonas fluorescens subsp.
      cellulosa and Pseudomonas sp. NCIB 8634.
AB  - The DNA of two previously isolated recombinant clones, one from Pseudomonas sp.
      NCIB 8634 (= Cellvibrio mixtus) (pPC71) and another from Pseudomonas fluorescens
      subsp. cellulosa (pPFC4) that express endoglucanase activity in E. coli was
      sequenced. Plasmid pPC71 had three open reading frames, two of which include
      portions of plasmid pBR322. The third open reading frame occurs entirely within
      the Pseudomonas DNA insert and encodes a protein with a molecular mass of 5845
      Da. The DNA insert in pPFC4 was found to contain an open reading frame (PFC-ORF)
      that encodes a protein of 32189 Da. The major endoglucanase produced in E. coli
      cells carrying pPFC4 is about 30,000 Da. It is concluded that PFC-ORF encodes
      this endoglucanase. Both ribosome and catabolite gene activator protein binding
      sites lie upstream from the initiating codon of PFC-ORF. An interesting feature
      of the PFC-ORF protein is the presence of amino acid motifs Val-Ser-Ser-Ser-Ser
      and Val-Val-Ser-Ser-Ser-Ser-Ser that occur within a 25 amino acid span.

PMID- 1366998
TI  - Biochemical fingerprints of Legionella spp. by the BIOLOG system: presumptive
      identification of clinical and environmental isolates.
AB  - Six Legionella strains were characterized with the BIOLOG identification system.
      A specific metabolic pattern for the six Legionella strains was observed after 24
      h. Several positive reactions were detected intermittently in all six strains
      tested. The possible application of the BIOLOG system for identification of
      Legionella spp. from environmental or clinical samples is discussed.

PMID- 1366997
TI  - Identification of indolepyruvic acid as an intermediate of rebeccamycin
      biosynthesis.
AB  - Experimental evidence is presented to demonstrate that indolepyruvic acid is an
      intermediate in the rebeccamycin biosynthetic pathway. [3-14C]Indolepyruvic acid
      was prepared and efficiently incorporated (8%) into rebeccamycin by Saccharothrix
      aerocolonigenes.

PMID- 1366999
TI  - Isolation and characterization of a cryptic plasmid from mesophilic aeromonads:
      potential as a cloning vector.
AB  - A 2.6 kb covalently closed circular plasmid has been isolated from clinical and
      environmental isolates of Aeromonas sobria and A. hydrophila. The possibility
      that the plasmid carries genetic determinants that mediate resistance to a
      variety of anti-microbial agents has been eliminated. The plasmid is stable at
      approximately 20-25 copies per chromosome equivalent which, together with its
      relatively small size and the presence of unique restriction sites, makes it a
      good candidate for development as a cloning vector.

PMID- 1367000
TI  - Electroporation-induced transformation of Escherichia coli: evaluation of a
      square waveform pulse.
AB  - Four strains of Escherichia coli were tested for electroporation-induced plasmid
      transformation using a high voltage pulse in a square waveform. Conditions for
      optimal transformation were determined for each strain and transformation
      frequencies found to be comparable to those reported previously for E. coli with
      a sinusoidal waveform of exponential decaying pulse.

PMID- 1367001
TI  - Generation of deletions in pTV1ts following transformation of Staphylococcus
      aureus protoplasts.
AB  - Plasmid pTV1ts was introduced into Staphylococcus aureus by transformation of
      protoplasts at frequencies ranging from 6.6 x 10(1) to 2.8 x 10(5) per micrograms
      of DNA when selection was made for resistance to chloramphenicol and
      erythromycin, respectively. Phenotypic analysis of regenerated transformants
      demonstrated three distinct classes. Analysis of the plasmid profiles of several
      isolates revealed that two classes harboured deleted pTV1ts derivatives.

PMID- 1367003
TI  - Boosting biocontrol efforts.

PMID- 1367002
TI  - Conjugal transfer of recombinant plasmids into gellan gum-producing and non
      producing variants of Pseudomonas elodea ATCC 31461.
AB  - The conjugal transfer of recombinant plasmids into a gellan gum-producing,
      rifampicin-resistant strain of Pseudomonas elodea and into one of its non
      producing variants, was studied in order to facilitate the cloning of gellan
      genes. The mobilization frequency of recombinant plasmids derived from pKT240,
      and of cosmid pJRD215 from Escherichia coli HB101 (hsdM), into the mucoid strain
      was below the values for the non-mucoid variant and decreased exponentially with
      plasmid size. Reducing the mating time on solid surfaces led to higher
      mobilization frequencies. Under optimal conditions, a gene bank (40-50 kb)
      constructed in the cosmid pJRD215 was efficiently mobilized into Gel- mutants
      during complementation experiments.

PMID- 1367004
TI  - A growth market for bioreactors?

PMID- 1367005
TI  - Reverse genetics: its origins & prospects.

PMID- 1367006
TI  - How FDA approved chymosin: a case history.

PMID- 1367007
TI  - Micro-imaging: in vivo veritas.

PMID- 1367009
TI  - Facilitated in vitro refolding of human recombinant insulin-like growth factor I
      using a solubilizing fusion partner.
AB  - We describe a new approach to refolding recombinant proteins in which an affinity
      fusion partner, consisting of two IgG-binding domains (ZZ) derived from
      staphylococcal protein A, is used to solubilize misfolded molecules before,
      during and after reduction and reoxidation. We show that human insulin-like
      growth factor I (IGF-I) can be refolded as a fusion protein at a concentration as
      high as 1-2 mg/ml without the use of denaturing agents. A process scheme suitable
      for large scale application is described in which the yield of correctly folded
      human IGF-I with full biological activity is substantially increased.

PMID- 1367008
TI  - Oligonucleoside methylphosphonates as antisense reagents.
AB  - Oligonucleoside methylphosphonates contain nonionic internucleotide bonds that
      resist degradation by cellular nucleases and allow the oligomers to be taken up
      intact by mammalian cells in culture. Antisense methylphosphonate oligomers
      targeted against cellular or viral mRNA initiation codon or coding regions or
      against precursor mRNA splice sites effectively and specifically inhibit mRNA
      expression in cells. The efficacy of antisense methylphosphonate oligomers can be
      enhanced by derivatization with functional groups that allow the oligomer to
      covalently cross-link with its targeted mRNA. These oligonucleotide analogs will
      be useful tools for studying and controlling gene expression and are also
      promising candidates for development as therapeutic agents.

PMID- 1367010
TI  - Bioconversion of n-octane to octanoic acid by a recombinant Escherichia coli
      cultured in a two-liquid phase bioreactor.
AB  - The alk genes from the catabolic OCT plasmid of Pseudomonas oleovorans, which
      encode the enzymes involved in the oxidation of n-alkanes to carboxylic acids,
      were introduced into E. coli W3110. The resulting recombinant converts n-octane
      in a two-liquid phase medium into the corresponding alkanoate and excretes this
      compound into the aqueous phase. The rate of octanoic acid production by the
      recombinant E. coli is equal to or better than the alkane oxidation rate of P.
      oleovorans, suggesting that two-liquid phase fermentations with E. coli might
      have future industrial applications.

PMID- 1367011
TI  - The development of virus-resistant alfalfa, Medicago sativa L.
AB  - We have generated more than 100 transgenic alfalfa plants, via Agrobacterium
      mediated gene transfer, from genotypes selected from five alfalfa cultivars.
      These plants express the genes for kanamycin resistance and for the coat protein
      of alfalfa mosaic virus (AMV). The strongest expressers accumulated nearly 500 ng
      coat protein per mg soluble leaf protein. AMV inoculation of protoplasts from
      these strong expressers indicated that they were resistant to infection by AMV,
      while protoplasts from plants containing about a hundred-fold less coat protein
      and from control untransformed plants were not. Transgenic alfalfa plants
      containing large amounts of coat protein were, likewise, resistant to AMV. These
      plants did not develop systemic infections following inoculation with up to 50
      micrograms/ml AMV, while inoculated control plants developed systemic infections
      following inoculation with as little as 10 micrograms/ml AMV. These results
      demonstrate that expression of the AMV coat protein gene confers resistance to
      AMV infection in transgenic alfalfa plants.

PMID- 1367012
TI  - Efficient KEX2-like processing of a glucoamylase-interleukin-6 fusion protein by
      Aspergillus nidulans and secretion of mature interleukin-6.
AB  - We have designed an expression vector for the secretion of human interleukin-6
      (hIL-6) in which the mature protein is fused through a spacer peptide, containing
      a KEX-2 like protein processing signal, to the entire Aspergillus niger
      glucoamylase (glaA) gene. Transformation of Aspergillus nidulans with this vector
      results in fungal strains secreting equimolar amounts of the glucoamylase and IL
      6 proteins. The KEX2-type processing signal, Lys-Arg, is recognized and cleaved
      efficiently by an enzyme present in A. nidulans resulting in the secretion of an
      authentic mature hIL-6 protein at levels of up to 5 mg/l.

PMID- 1367013
TI  - The ethanol utilization regulon of Aspergillus nidulans: the alcA-alcR system as
      a tool for the expression of recombinant proteins.

PMID- 1367014
TI  - Expression of heterologous proteins in Aspergillus.
AB  - Filamentous fungi, in particular those of the genus Aspergillus have been well
      exploited for their ability to produce high levels of extracellular proteins in
      an inexpensive manner. Since many human proteins with the potential to be used
      therapeutically are secreted and require post-translational modification for
      biological activity, eukaryotic expression-secretion systems have been targeted
      for development. Recent developments in DNA-mediated transformation systems have
      allowed the utilization of Aspergillus as a host for the production of
      recombinant proteins. Several features such as well-characterized genetics and
      the availability of many mutants make Aspergillus nidulans the organism of choice
      for development of expression secretion systems. Recombinant strains contain
      integrated expression cassettes often in multiple copy, which are mitotically
      stable. In this review, we discuss the recent progress made in the use of
      Aspergillus as expression secretion hosts for the production of proteins of
      therapeutic significance.

PMID- 1367015
TI  - Enzyme production by recombinant Trichoderma reesei strains.
AB  - The production of both homologous and heterologous proteins with the cellulolytic
      filamentous fungus Trichoderma reesei is described. Biotechnically important
      improvements in the production of cellulolytic enzymes have been obtained by
      genetic engineering methodology to construct strains secreting novel mixtures of
      cellulases. These improvements have been achieved by gene inactivation and
      promoter changes. The strong and highly inducible promoter of the gene encoding
      the major cellulase, cellobiohydrolase I (CBHI) has also been used for the
      production of eukaryotic heterologous proteins in Trichoderma. The expression and
      secretion of active calf chymosin is described in detail.

PMID- 1367016
TI  - Proteolytic events in the processing of secreted proteins in fungi.
AB  - Secreted heterologous proteins have been found to be produced much less
      efficiently by fungi than secreted homologous ones. This could be due, at least
      in part, to proteolytic cleavage by site-specific endoproteases of the secretory
      pathway, similar to the yeast KEX2 protease and the mammalian dibasic
      endoproteinases found in secretory pathways. Mature secreted fungal proteins may
      be protected from such cleavage due to the absence of cleavable sites in exposed
      regions. A comparison of the dipeptide distributions of 33 secreted and 34
      cytoplasmic proteins from fungal producers of extracellular enzymes indicated a
      significant bias for some doublets, including the basic dipeptides Lys-Arg, Arg
      Arg and Arg-Lys which have also been demonstrated to be KEX2 substrates. Other
      combinations were also found to be rare in secreted proteins, which could
      indicate either a broader specificity of the considered endopeptidase, or the
      presence either in the secretory organelles or among the secreted proteins of
      additional proteases with different specificities. Experimental evidence that the
      Lys-Arg site is processed in Tolypocladium geodes was provided by cloning a
      synthetic prosequence upstream of a phleomycin resistance (Sh ble) gene and
      analyzing the N-terminus of the corresponding protein purified from the culture
      supernatant. This system also provides a tool for further studies of specific
      proteases of fungi.

PMID- 1367018
TI  - Introduction: the current status of immobilized protein technology.

PMID- 1367019
TI  - Immobilization of proteins by noncovalent procedures: principles and
      applications.

PMID- 1367017
TI  - Identification and expression of the ACV synthetase gene.
AB  - The gene coding for ACV synthetase has recently been identified and cloned.
      Analysis of its structure and expression, along with similar studies of other
      genes involved in beta-lactam biosynthesis, should lead to a better understanding
      of the molecular basis of regulation of the pathway and the possibility of
      modifying yield and diversity of fungal antibiotics.

PMID- 1367020
TI  - Commercially available supports for protein immobilization.

PMID- 1367021
TI  - Determination of coupling yields and handling of labile proteins in
      immobilization technology.

PMID- 1367022
TI  - Immobilized enzymes in organic solvents.

PMID- 1367023
TI  - Immobilized enzyme electrodes as biosensors.

PMID- 1367024
TI  - Therapeutic applications of immobilized proteins and cells.

PMID- 1367025
TI  - Immobilized microbial and animal cells as enzyme reactors.

PMID- 1367026
TI  - Industrial applications of immobilized proteins.

PMID- 1367027
TI  - Covalent and coordination immobilization of proteins.

PMID- 1367028
TI  - Biosensor system for continuous flow determination of enzyme activities. II.
      Simultaneous determination of plural enzyme activities.
AB  - A biosensor system for continuous flow determination of plural enzyme activities
      was prepared from the combination of two pyruvate sensors, a prereactor and a
      flow cell. This system was applied to the simultaneous determination of lactic
      dehydrogenase (LDH) and glutamic-pyruvic transaminase (GPT) activities in the
      same sample. These enzyme activities can be determined by measuring pyruvate
      produced by the enzyme reactions as follows. The amount of pyruvic acid can also
      be determined from the amount of oxygen consumed upon oxidation of pyruvic acid
      by pyruvate oxidase. (Formula: see text). Therefore, both of the detectors for
      the determination of lactic dehydrogenase and glutamic-pyruvic transaminase
      activities were prepared from the combination of a pyruvate oxidase membrane and
      an oxygen electrode. Pyruvate oxidase was covalently immobilized on a membrane
      prepared from cellulose triacetate. A linear relation was obtained between the
      output current and LDH or GPT activities in the range of 50 to 3,600 IU l-1 or 6
      to 1,000 IU l-1, respectively. Each assay of these enzyme activities was
      completed within 15 min. The results obtained had a precision of ca. 4%. The
      sensor was stable for more than 25 days at 5 degrees C.

PMID- 1367029
TI  - Stabilizing effect of penicillin G sulfoxide, a competitive inhibitor of
      penicillin G acylase: its practical applications.
AB  - We have found that penicillin G sulfoxide (pen G SO) behaves as a general
      stabilizing agent of two bacterial penicillin G acylases (PGAs) from E. coli and
      from K. citrophila), and this role is related to a strong inhibitory effect on
      the enzymes. The stabilizing effect has been observed during two different
      inactivation processes: (i) thermal inactivation of soluble enzymes at alkaline
      pH, and (ii) inactivation of immobilized enzymes as a consequence of covalent
      multiinteraction with highly activated agarose aldehyde gels. At the same time,
      pen G SO behaves as a strong competitive inhibitor of these two enzymes. The
      inhibition constant is more than 10-fold lower than the one corresponding to
      another smaller competitive inhibitor, phenylacetic acid (PAA), the structure of
      which is exactly the acyl donor moiety corresponding to pen G SO. In turn, PAA
      hardly exerts any stabilizing effect on PGAs. The stabilizing effect of pen G SO
      allowed the preparation of derivatives of these PGAs preserving full catalytic
      activity in spite of being 1,400- and 650-fold more stable than the corresponding
      soluble or one-point attached immobilized enzymes.

PMID- 1367030
TI  - Genetic engineering of Trichoderma to produce strains with novel cellulase
      profiles.
AB  - Genetic engineering has been used to modify the proportion of different
      cellulases produced by a hypercellulolytic Trichoderma reesei mutant strain. A
      general expression vector, pAMH110, containing the promoter and terminator
      sequences of the strongly expressed main cellobiohydrolase 1 (cbh1) gene was used
      to overexpress a cDNA coding for EGI, the major endoglucanase (1,4,beta-D-glucan
      glucanohydrolase, EC 3.2.1.4). An in vitro modified cbh1 cDNA, incapable of
      coding for active enzyme, was used to inactivate the major cellobiohydrolase (1,4
      beta-D-glucan cellobiohydrolase, EC 3.2.1.91) gene. In this way, new strains
      producing elevated amounts of the specific endoglucanase 1 (EGI) and/or lacking
      the major cellobiohydrolase (CBHI) were produced, and these have been further
      characterized.

PMID- 1367031
TI  - Immobilization of invertase by encapsulation in polyelectrolyte complexes.
AB  - Free and polystyrene-bound invertase from Saccharomyces cerevisiae were
      encapsulated within symplex membranes which were composed of cellulose sulfate as
      the polymeric anion and poly(dimethyldiallylammonium chloride) as the polymeric
      cation. The kinetics and the performance of the encapsulated enzyme preparations
      have been compared to the free enzyme employing the hydrolysis of sucrose. The pH
      and temperature optima were only slightly affected by the encapsulation. The
      kinetic constants, however, were changed by the encapsulation as a result of
      diffusional limitation. Encapsulated invertase showed a high storage stability
      and a high operational stability if low substrate concentrations were applied.
      The coimmobilization of invertase with living cells, which are not capable of
      utilizing sucrose, in the described capsules, opens many possibilities in
      fermentation technology.

PMID- 1367032
TI  - Formation of peptide bonds by carboxypeptidase c from orange leaves.
AB  - Carboxypeptidase c partially purified from orange leaves was studied as a
      catalyst for enzymatic peptide synthesis. Various N-protected ester- and
      nucleophile compounds were evaluated in order to determine the substrate
      specificity. For further characterization of the synthetic reaction, optimum pH
      and the influence of the N-terminal protecting group were studied. Kinetic
      investigations revealed considerable differences in Km and Vmax for the
      nucleophile when the N-terminal protecting group of the substrate was varied.

PMID- 1367033
TI  - Diffusion in immobilized-cell gels.
AB  - The relationship between the diffusion coefficient, the effective diffusion
      coefficient and the partition coefficient for a solute in a cell-containing gel
      is discussed. The use of correlation equations that are based on some kind of
      physical model is recommended when the effect of cell concentration on diffusion
      is interpreted.

PMID- 1367035
TI  - Overproduction of an acetylxylan esterase from the extreme thermophile
      "Caldocellum saccharolyticum" in Escherichia coli.
AB  - The xynC gene coding for an acetylxylan esterase from the extreme thermophile
      "Caldocellum saccharolyticum" was overexpressed in Escherichia coli strain RR28
      by cloning the gene downstream from the lacZ promoter region of pUC18 (pNZ1447)
      or downstream from the temperature-inducible lambda pRpL promoters of pJLA602
      (pNZ1600). The protein formed high molecular weight aggregates in induced cells
      of RR28/pNZ1600 but not in RR28/pNZ1447. The enzyme constituted up to 10% of the
      total cell protein and was located in the cytoplasmic fraction of RR28/pNZ1447.
      The acetyl esterase was most active at pH 6.0 and 70-75 degrees C with a half
      life of 64 h at 70 degrees C and 30 h at 80 degrees C, respectively.

PMID- 1367034
TI  - Synthesis and secretion of hirudin by Streptomyces lividans.
AB  - To examine the secretory production of heterologous proteins by Streptomyces
      lividans, we fused the DNA encoding the signal peptide of the alpha-amylase
      inhibitor tendamistat, derived from S. tendae with a synthetic gene encoding the
      thrombin inhibitor hirudin. The analysis of secretion by immunoblots revealed an
      efficient translocation of hirudin through the membrane, with no detectable
      immunoreaction among the cellular proteins. The secreted hirudin was stable in
      the shaking culture for about 6 days. A comparison of the hirudin secreted by S.
      lividans and recombinant reference hirudin from yeast by immunoblots and thrombin
      inhibition assays shows that hirudin from Streptomyces has a lower specific
      activity, which may be due to a different aminoterminal sequence or to inexact
      processing of the precursor.

PMID- 1367036
TI  - A semi-homogeneous amperometric immunosensor for protein A-bearing Staphylococcus
      aureus in foods.
AB  - A semi-homogeneous amperometric immunosensor specific to the protein A of
      Staphylococcus aureus was developed using direct electrochemical detection of
      phenol produced by alkaline phosphatase from phenyl phosphate. The immunosensor
      could reliably detect strains of protein A-bearing S. aureus in pure cultures at
      ca. 10(4) cfu/ml, and at ca. 10(5) cfu/g or ml in various food samples. Due to
      its semi-homogeneous nature, the system was very simple, easy to operate, and
      labour-saving. The good correlation between the amperometric current generated by
      the immunosensor and plate counts illustrated the potential usefulness of this
      simple system. It proved to be a reliable 24-h detection method for food samples
      containing very low numbers of protein A-bearing S. aureus after pre-enrichment,
      as it was able to detect cells that could not directly be enumerated by plate
      counts.

PMID- 1367037
TI  - Reduced cell viability in vitro following exposure to a routine laboratory
      disinfectant. A cautionary note.

PMID- 1367038
TI  - Multiple episodes of induced secretion of human growth hormone from recombinant
      AtT-20 cells.
AB  - Recombinant AtT-20 cells expressing human growth hormone (hGH) secreted the
      hormone at a constant, basal rate of 0.3-0.5 ng/10(5) cells-hour when exposed to
      medium without secretagogues. When triggered with 8 bromo-cyclic AMP, cells
      secreted hGH at an initial rate of 1.7 ng/10(5) cells-hour while intracellular
      hGH declined sharply. Upon extended exposure to secretagogue, secretion decreased
      gradually to the basal rate and intracellular hGH stabilized at a value 40% the
      initial. In cells switched from secretion to growth medium, the total rate of hGH
      accumulation intracellularly and in medium was 2.2 times that observed with cells
      never exposed to secretagogue; however, only a fraction of the hormone was stored
      intracellularly and the rest was secreted. When cells were exposed alternately to
      growth and secretion medium, induced cells secreted at rates at least two times
      higher than uninduced controls during the first five cycles. The induced response
      deteriorated with time, however, in parallel with outgrowth of attached cells by
      foci of round cells, and by the eighth cycle induced secretion did not occur.
      Operational modifications that may improve the performance of cycling schemes are
      discussed.

PMID- 1367039
TI  - Purification and some properties of proliferation suppressing factor from human
      lung adenocarcinoma PC-8.
AB  - Extracts by 3 M KCl from a human lung adenocarcinoma cell line, PC-8, suppressed
      the proliferation of phytohemagglutinin activated lymphocytes. The proliferation
      suppressing factor (PSF) was purified from the extracts by ammonium sulfate
      precipitation, gel filtration and ion exchange chromatography. The purified PSF
      had a molecular weight of 50 kDa by SDS-PAGE and was acid- and heat-labile. Since
      the PSF also suppressed the proliferation of three established human cell lines,
      it is unlikely that the PSF hinders the interaction between lymphocytes and
      mitogens.

PMID- 1367040
TI  - A two-compartment cell entrapment bioreactor with three different holding times
      for cells, high and low molecular weight compounds.
AB  - A new bioreactor for animal cell cultivation employs two compartments for cells
      and medium respectively. The two chambers are separated by an ultrafiltration
      membrane. Cells and solution of collagen or collagen/chitosan mixture were loaded
      to the cell chamber and were allowed to form gel inside. Contraction of the cell
      laden gel occurred subsequently to create a new zone in the cell chamber. In such
      a bioreactor cells are retained in the reactor, the high molecular product(s)
      accumulate in the cell chamber, while the small molecular weight nutrients and
      metabolites are replenished and removed from the medium chamber. By adjusting the
      flow rates for cell and medium chambers, the resident time for cells, high and
      low molecular weight components of the system can be manipulated separately. The
      new bioreactor, in both flat-bed and hollow-fiber configurations, was used to
      cultivate recombinant human cell, 293, for Protein C production over 60 to 90
      days.

PMID- 1367042
TI  - The effect of bioreactor configuration on production of HIV and cell-virus
      interaction.
AB  - In an attempt to establish a bioreactor system for generation of HIV that is
      practicable, efficient, biologically contained, and capable of scale up, the
      production of two strains of this virus was examined in suspension culture and
      the 'Porosphere' fixed bed system. HIV 1 and HIV 2 were grown successfully in
      both these types of reactor. The porosphere reactor theoretically appears to
      offer a better environment for HIV production, but evidence for significantly
      improved yields from this system, compared to suspension, was equivocal. However,
      this configuration facilitated media changes during culture. The data clearly
      showed that the culture system and cell environment significantly affected cell
      virus interrelationships. Switches between lytic--and persistent--type
      infections, and changes in the virus population were observed.

PMID- 1367041
TI  - A new human fusion partner, HK-128, for making human-human hybridomas producing
      monoclonal IgG antibodies.
AB  - A hypoxanthine-aminopterin-thymidine (HAT) sensitive human fusion partner cell
      line, HK-128 was established from a human plasmacytoma line, LICR-LON-HMy2
      (HMy2). The HK-128 cells showed a 100% cloning efficiency. Fusion efficiency of
      HK-128 was so high that one hybridoma cell was produced by fusion of 10(5) cells
      of HK-128 with lymphocytes, obtained from lymph nodes of breast cancer patients.
      About 90% of the resulted hybridomas were IgG producers. The remainder revealed
      IgM producing activity, which was lost by long term culture. This result
      indicates that the HK-128 cell line has an advantage for making hybridoma cells
      producing IgG. Among ca. 7,000 hybridomas obtained by fusion of HK-128 with
      lymphocytes of a breast cancer patient, we could establish a hybridoma cell line
      which produced IgG specifically reacting to a human breast cancer cell line, MCF
      7.

PMID- 1367044
TI  - A compatible support system for cell culture in biomedical research.
AB  - The lack of a suitable system to culture epithelial cells for a long period under
      a luminal-antiluminal medium gradient, was the reason to develop a new system. It
      consists of an interchangeable sheet of permeable support material, which is set
      in place by two tight fitting holding rings. For special demands the supports can
      be coated with extracellular matrix proteins improving cellular attachment and
      terminal differentiation. The handling of the sheets by forceps proceeds easily
      and quickly, thus fastening the transfer of cultured cells without additional
      manipulations. The sheets can be transferred to a newly developed microperfusion
      chamber on which an apical and a basal perfusion over a long culture period
      parallel to a transepithelial electrophysiological registration becomes possible.
      The chamber has an extremely low amount of fluid dead space. The separate
      perfusion of cultured cells under isotonic, hypotonic or hypertonic conditions
      opens new possibilities. Thus, culture can be performed under most natural
      conditions e.g., that found within the kidney.

PMID- 1367043
TI  - Efficient expression of human beta-interferon in Namalwa KJM-1 cells adapted to
      serum-free medium by a dhfr gene coamplification method.
AB  - We previously reported the expression of human beta-interferon (beta-IFN) (Miyaji
      et al., 1989) and human lymphotoxin (Miyaji et al., 1990) in Namalwa KJM-1 cells
      adapted to serum-free medium. To establish an efficient gene expression system, a
      dihydrofolate reductase (dhfr) gene coamplification method was applied to this
      cell line. A beta-IFN expression plasmid was introduced with a dhfr expression
      plasmid into KJM-1 and methotrexate (MTX)-resistant derivatives were selected by
      a stepwise increase of MTX concentration. Among them, derivatives which showed
      higher expression levels of beta-IFN than that achieved by the parental
      transformants were obtained, suggesting that a dhfr gene coamplification method
      can be used for efficient expression of foreign genes in KJM-1 which contains
      endogenous dhfr genes. Then, an improved beta-IFN expression vector was
      constructed, which contains a dhfr transcription unit. This plasmid was
      introduced into KJM-1 and then, MTX-resistant derivatives were selected. Among
      them, the highest producer, clone 40-10-24, secreted beta-IFN at a level as high
      as 5 micrograms/ml, which is about 100-fold higher than that obtained by the G418
      resistant parental transformants. In addition, beta-IFN produced by recombinant
      KJM-1 cells had the same molecular weight of that produced by fibroblasts.

PMID- 1367045
TI  - 3-Amino-6-methoxy-9-(2-hydroxyethylamino) acridine: a new fluorescent dye to
      detect Mycoplasma contamination in cell cultures.
AB  - A new fluorescent acridine orange derivative, 3-amino-6-methoxy-9-(2
      hydroxyethylamino) acridine (AMHA), has been applied to Hela cells in order to
      set up appropriate conditions for the detection of mycoplasma contaminations.
      Since AMHA staining reveals intensely fluorescent nuclei and slight fluorescent
      cytoplasm, we can visualize and localize mycoplasma contamination on each cell.
      In combination with a shortened Chen's staining method (1977), AMHA should allow
      a better detection of mycoplasma in animal cell cultures than the well
      established Hoechst dye.

PMID- 1367046
TI  - The advantage of the aggregate culture of isolated ovarian cell types over the
      monolayer culture.
AB  - Ovarian cells such as theca interna, granulosa and corpus luteum cells were
      isolated from pig ovaries and cultured in Erlenmayer flasks (25 ml) containing
      3.5 ml of culture medium. The media were replaced every second day and frozen to 
      20 degrees C for later steroid analysis. The reaggregation of cells was completed
      within 2-3 days and this was then followed by a period of cell migration. During
      the subsequent 5-6 day period the reaggregates became larger. The best results
      were obtained in cultures of isolated theca alone and in combination with
      granulosa cells, as well as of early corpus luteum cells. Granulosa cells did not
      aggregate as easily or as completely as the corpus luteum cells. All types of
      cells investigated were able to secrete progesterone into the culture medium.
      They secreted more progesterone and for a longer time than cells cultured as
      monolayers. The aggregate culture seems to be a good model to study the secretion
      of ovarian cells, by creating the tri-dimensional, and thus more physiological,
      culture system.

PMID- 1367047
TI  - Serum-free media and cell cultures. Introductory remarks.

PMID- 1367048
TI  - Nutrient optimization for high density biological production applications.

PMID- 1367049
TI  - Strategies for optimising serum-free media.

PMID- 1367051
TI  - Production of recombinant proteins in serum-free media.
AB  - The advantages of serum-free culture for the manufacture of recombinant
      biopharmaceuticals from mammalian cells are reviewed. The process favoured is fed
      batch serum-free cell culture. This process is applicable to the majority of cell
      lines, is practical on the large scale, gives the lowest manufacturing cost, and
      can be carried out without the use of any serum.

PMID- 1367050
TI  - Serum-free culture of carcinoma cell lines.

PMID- 1367052
TI  - Optimization of serum-free fermentation processes for antibody production.
AB  - Serum free fermentation procedures of cell cultures have got a wide application
      in production of biochemicals. But, cells cultured in serum free media in general
      are more sensitive to changes in culture condition, especially to nutrient
      limitation. There are no substances from serum which can support the cells when
      conditions are changing. In this study special attention is directed to amino
      acid utilization of mouse hybridoma in batch, chemostat and perfusion
      fermentations. Detailed data are presented which show the considerable difference
      of amino acid consumption rates in different fermentation modes. Already, in
      batch mode there are differences of the two investigated mouse hybridoma cell
      lines, although they are derived from the same myeloma line. In chemostat running
      at a dilution rate representing maximal growth rate most of the consumption rates
      are significant higher than in batch. On the other hand, in perfusion mode the
      rates are lower than in batch. This indicates clearly the different conditions of
      the fermentation modes. Therefore, it is necessary to develop serum free
      processes under the desired production conditions. An accurate analysis of the
      process is strongly recommended.

PMID- 1367053
TI  - Serum-free medium for fermentor cultures of hybridomas.
AB  - Hybridomas lend themselves particularly well to large scale cultivation
      techniques since they grow as single cells in suspension without requiring
      attachment to a substrate. Furthermore, many cell strains have been adapted to
      grow in serum-free (SF) media to a similar cell density and antibody production
      as in serum containing media. This review will concern itself mainly with the
      cultivation of hybridomas in SF-media in bioreactors of various types with the
      ultimate goal of producing large quantities of monoclonal antibodies (mAb).

PMID- 1367055
TI  - Large scale mammalian cell culture technology.

PMID- 1367054
TI  - Physiological enhancement of immunoglobulin production of hybridomas in serum
      free media.

PMID- 1367056
TI  - Cell banking.
AB  - The use of cultured cells (diploid strains or continuous cell lines) to produce
      biopharmaceuticals provides a level of standardization to the manufacturing
      process that cannot be attained by the more traditional methods of biological
      extraction from animal or human fluids, tissues, or primary cells. The key to
      this advantage is the ability to cryopreserve the production cell line as a
      master cell bank. This bank serves as the common starting source of a given
      product for the lifetime of the manufacture of that product. Since the MCB is the
      common and only starting source, it can be exhaustively characterized with regard
      to contamination by adventitious and endogenous agents. Assays can be developed
      for cellular components that are potential contaminants of the product. The
      removal of these components during product purification can be validated and
      their removal confirmed by rigorous quality control. In conclusion, characterized
      cell banks are central to the standardization of biopharmaceutical manufacturing
      processes and give rise to the production of high-quality products not attainable
      by the traditional methods of extraction of product from sources which are
      continually changing.

PMID- 1367058
TI  - Expression of cloned proteins in mammalian cells: regulation of cell-associated
      parameters.

PMID- 1367057
TI  - Use of recombinant DNA technology for engineering mammalian cells to produce
      proteins.
AB  - The recent advances in molecular biology have merged with somatic cell genetics
      and cell biology to allow mammalian cells to be extremely useful for the
      expression of foreign genes. This chapter has focused primarily on the approaches
      and potential limitations to high-level expression of proteins in mammalian
      cells. Future developments will involve the modification of mammalian cells in
      order to increase the efficiency of the various steps in protein processing and
      secretion. The ability to genetically engineer mammalian cells to produce high
      levels of desired proteins is presently complemented by advances in biochemical
      engineering which involve the ability to grow mammalian cells in very large
      volumes or at very high densities with reduced serum requirements. As a result,
      the cost for production of gram quantities of a protein from a mammalian host
      cell are approaching the cost of proteins from a mammalian host cell are
      approaching the cost of proteins similarly derived from microbial systems with
      all the advantages that mammalian systems afford.

PMID- 1367059
TI  - Assay requirements for cell culture process development.
AB  - Because the structural parameters which influence product "quality" will vary
      from protein to protein, the screening methods used during development of each
      production process will also differ. Thus, not all of the methods described above
      will be needed for each product. One of the challenges of cell culture process
      development is choosing the correct structural features to monitor. The next
      level of process development may involve on-line control of many of the
      parameters discussed above. This would allow product quality-driven manipulations
      of culture conditions. The major factor limiting this advance may not be the
      techniques for real-time analysis, but rather a more thorough understanding of
      the structural features which describe a high-quality pharmaceutical protein.

PMID- 1367060
TI  - Nonperfused attachment systems for cell cultivation.
AB  - The pressing need for large-scale culture methods has prompted efforts to develop
      vessels which will accommodate the growth of large numbers of anchorage-dependent
      cells. The large-scale "cell factories" have been used to grow viruses for
      vaccine production, nucleic acid studies, and various cancer research projects.
      Two particular types of culture vessels used for large-scale production of
      anchorage-dependent cells were discussed and examples of their use in vaccine
      production given. Development of these large-scale culture systems has enabled
      the pharmaceutical companies to (1) meet the ever-increasing demands worldwide
      for vaccine, (2) employ a production process that produces a cost-efficient
      vaccine product in cell culture, and (3) produce large volumes of bulk vaccine at
      a single campaign, thus allowing multiple usage of a single production unit over
      the course of a year. The type of large-scale culture vessel used depends on the
      purpose of the culture and the type of cells that are to be grown in the vessel.
      The unit process vessel, with its multidisks, provides superior surface area, but
      because of the stainless steel housing, the cells cannot be monitored
      microscopically. Additionally, the unit process vessel can be equipped with a
      jacket for precise temperature regulation and thus eliminate the need for
      incubators. The roller bottles, on the other hand, allow microscopic monitoring
      of the growing cells but are limited in surface area available for growth, and
      the volume of harvest fluid obtainable from a bottle is very limited. It should
      be noted that handling of roller bottles is labor-intensive and requires many
      more manipulations and hence more personnel than employing unit process-type
      vessels for vaccine-manufacturing operations. The use of mass cultivation
      techniques in cancer research has also been of immense benefit. The production of
      large numbers of neoplastic cells has provided researchers with the raw materials
      to perform molecular biology experiments such as DNA sequencing, which required
      milligram quantities of cells before sufficient quantities of DNA could be
      isolated to allow sequencing studies. Additionally, the technique of mass
      cultivation also provided sufficient quantities of cells for inoculation into
      either nude mice or immunosuppressed hamsters in an attempt to determine the
      tumor induction capacity of the cultured cells. Additional characterization
      studies which require large numbers of cell, enzyme, and isoenzyme profiles can
      also be performed on cells grown in roller bottle cultures. There are numerous
      factors which limit the productivity of mass cultivation systems and the
      scientist should be aware of their existence.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1367061
TI  - Perfusion systems for cell cultivation.

PMID- 1367062
TI  - Suspension culture of mammalian cells.
AB  - Mammalian cell suspension culture systems are being used increasingly in the
      biotechnology industry. This is due to their many advantages including simplicity
      and homogeneity of culture. Suspension systems are very adaptable (e.g., for
      microcarrier, microencapsulation, or other methods of culture). Their engineering
      is thoroughly understood and standardized at large scale, and automation and
      cleaning procedures are well established. Suspension systems offer the
      possibility of quick implementation of production protocols due to their ability
      to be scaled easily once the basic culture parameters are understood. The only
      main disadvantage of the suspension culture systems to date is their
      inapplicability for the production of human vaccines from either primary cell
      lines or from normal human diploid cell lines (Hayflick et al., 1987 and
      references therein). One of the great advantages of suspension culture is the
      opportunity it provides to study interactions of metabolic and production
      phenomena in chemostat or turbidostat steady-state systems. Furthermore, in
      suspension culture systems from which cell number and cell mass measurements are
      easy to obtain, rigorous and quantitative estimations of the effects of growth
      conditions or perturbations of metabolic homeostasis can be made. Such studies
      can speed up the development of optimal processes. With our increasing
      understanding of factors influencing expression in mammalian cells (Cohen and
      Levinson, 1988; Santoro et al., 1988) and the direct application of new methods
      in suspension culture (Rhodes and Birch, 1988), its usefulness and importance is
      likely to increase in the future. In this chapter, we have described some of the
      potential uses of the various suspension culture systems and have covered most of
      the established technology and literature. Due to the rapid developments and
      needs in the biotechnology industry and the versatility of suspension culture
      systems, it is probable that many more variations on this theme will evolve in
      the near future at both the pilot and production scales.

PMID- 1367063
TI  - Microcarrier culture systems.

PMID- 1367064
TI  - Microencapsulation of mammalian cells.

PMID- 1367065
TI  - Continuous culture with macroporous matrix, fluidized bed systems.

PMID- 1367066
TI  - Downstream processing of proteins from mammalian cells.
AB  - Less than a decade ago, the use of continuous mammalian cell lines for the
      production of cloned proteins was considered strictly a research tool. At that
      time, few thought it possible to allay the many safety concerns associated with
      transformed cells. It soon became clear that mammalian expression systems had
      numerous advantages over bacteria for production of therapeutic proteins,
      initiating a multidisciplinary effort to address these concerns in a thorough and
      reliable manner. The success of these efforts is exemplified by the emergence of
      product molecules into the market. Today, there are seven recombinant human
      therapeutics that have received FDA approval. Almost half of them (OKT3, t-PA,
      and EPO) are produced in mammalian cells, with the remainder produced in bacteria
      (insulin, growth hormone, and alpha-interferon) or yeast (hepatitis vaccine). At
      least a dozen more recombinant cell culture products are in advanced human
      clinical trials. With the accumulation of data and experience, continuous
      mammalian cell lines will no doubt be the preferred hosts for many future
      products of biotechnology.

PMID- 1367067
TI  - Management of process technology.
AB  - A successful manufacturing scale cell culture process has as its basis a well
      designed process. However, even the best designed large-scale process can become
      unreliable if not managed properly. The primary element to successful management
      of all large-scale processes is the careful attention to the details, especially
      the most important ones. The second element that requires serious consideration
      is the operation of that process within the confines of current regulatory
      environments. The major considerations are: 1. Adequate raw material
      specifications and testing. 2. Facility and equipment design that maximizes
      operational success and meets current regulatory requirements. 3. Thoroughly
      written procedures covering all aspects of operation and maintenance, and
      supported by a thorough documentation and review system. 4. A dedicated staff
      with a thorough understanding of systems and the importance of operational
      details. 5. Continual training and retraining programs. 6. Sound process and
      facility validation programs. 7. Comprehensive preventive maintenance programs.
      8. Thorough understanding of process and facility trends, and the expected and
      acceptable ranges of results. 9. Development of sound procedures and practices
      that minimize batch losses and permit operation within current regulatory
      requirements. 10. Thorough and continual monitoring of all critical process
      parameters. 11. Process scheduling to minimize batch jeopardy or loss while
      maximizing throughout. 12. Maintenance of the appropriate environmental
      conditions of the plant and general cleanliness of plant and equipment. 13.
      Adequate batch loss prevention programs. 14. Adequate troubleshooting programs.
      15. Adequate support organization and facilities both internally and externally
      to plant operations. With the appropriate application of sound process design and
      management principles, and with operational experience, large-scale cell culture
      process plants can be operated at success rates that exceed 95%.

PMID- 1367068
TI  - Monitoring and control of animal cell bioreactors: biochemical engineering
      considerations.

PMID- 1367069
TI  - Methods for the detection of adventitious viruses in cell cultures used in the
      production of biotechnology products.
AB  - The possibility for viral contamination exists in established cultures as well as
      in primary cultures. The use of established genetically engineered cultures in
      the production of biologicals for human use requires that these cultures be
      monitored for adventitious viral agents. Among the methods used for this purpose
      are animal inoculation and in vitro assays which provide a broad-spectrum screen
      for viral agents.

PMID- 1367070
TI  - Process validation for cell culture-derived pharmaceutical proteins.
AB  - Principles of process validation are extremely powerful tools in assurance of
      product quality. They are especially useful for reducing those risks not easily
      measured routinely during production. When combined with effective process and
      facility design principles, characterization of cell banks and products,
      appropriate lot release tests, and adherence to cGMP, safe cell culture
      biologicals can be prepared in a reliable manner.

PMID- 1367071
TI  - Design and construction of manufacturing facilities for mammalian cell-derived
      pharmaceuticals.

PMID- 1367072
TI  - Large-scale propagation of insect cells.
AB  - Cultured insect cells have many uses in agriculture and medicine. They can be
      used in the diagnosis and isolation of a number of viruses infecting both animals
      and plants and for the laboratory study of these viruses. Large-volume culture of
      insect cells has been envisioned as a way of producing viruses for use in
      controlling insect pests and for the production of viral antigens for vaccine
      preparations. Recently they have become a potentially valuable way of producing a
      variety of proteins for human and veterinary medicine using the genetically
      engineered baculovirus expression vectors. The development of satisfactory cell
      lines and culture methods has proceeded at a slow, irregular pace, inhibited by
      the lack of knowledge of the physiology of the insect, its small size, and often
      by the lack of consistent, adequate support for the necessary developmental
      research. However, now that the basic culture systems are available, cell lines
      have been developed or can easily be developed for most needs. Suitable media are
      available and recent developments in refining existing media formations have
      resulted in low-cost media containing little protein to interfere with down
      stream processing of cellular metabolites. Future developments are likely to
      further improve the media formulations and lower the cost. Technical problems
      relating to oxygen demand and cell fragility that inhibited the continued
      development of large-volume culture systems beyond the laboratory a few years ago
      now appear to be solved or at least are solvable. The successful culture of the
      Spodoptera cells in bioreactors of 40-liter capacity indicates that means of
      producing insect cells or their metabolic products on a commercial scale can be
      made economically feasible.

PMID- 1367073
TI  - Large-scale animal cell culture: a biological perspective.
AB  - It is generally recognized that no one cell culture system can be universally
      applied to all cell types commonly used for biopharmaceutical manufacture. The
      analogous concept that no single cell type may be useful for the expression of
      all biopharmaceutical products may also gain credence in the biotechnology
      community. It may be that like specialized bioreactors, there will come to exist
      a variety of cell types that will be used for the production of different types
      of biopharmaceutical products. In addition, it may not be enough in the future
      just to demonstrate the stability of expression of the amino acid backbone of the
      protein only; the carbohydrate portion of the molecule may become the subject of
      real scrutiny. Questions such as how the carbohydrate side chain affects the
      performance of the molecule in vivo are being asked of more DNA constructs. The
      next question becomes, how can we control the expression of carbohydrate moieties
      on the molecule? Such questions are in the future of the biotech manufacturing
      field. Aside from those examples mentioned above dealing with the insertion of
      receptors, other more subtle attempts at modifying cellular metabolism are taking
      place. It was reported at a recent meeting that the sialyltransferase gene was
      inserted into a CHO line which did not normally express this enzyme (116). The
      transfected line was capable of expressing the transferase and, more importantly,
      the enzyme functioned correctly in sialylating glycoproteins. Other very complex
      relationships exist between the substratum and the cell that could have very
      direct consequences on culture maintenance. For example, researchers recently
      published results indicating that collagenase synthesis and secretion is
      stimulated in rabbit fibroblasts by autocrine factors. They determined that these
      autocrine proteins had sequence homology to serum amyloid-A and beta-2
      microglobulin. It may be that using serum supplements in the medium in those
      systems that couple fibroblast and collagen substratum may not be prudent,
      especially for long-term culture. The traditional selection of a cell type for
      expressing heterologous proteins has generally been limited to the more "common"
      cell types such as CHO cells, C127 cells, and myeloma cells. In many cases these
      cell types were selected because there was a great deal of preexisting literature
      on the cell type (i.e., "cookbook" methods of transfection for the cell) or the
      cell was simply being carried in the lab at the time the effort was made to
      express a biopharmaceutical product.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1367075
TI  - Objectives for extractive bioconversion.

PMID- 1367074
TI  - Mammalian cell physiology.

PMID- 1367076
TI  - Cultivation using membrane filtration and cell recycling.

PMID- 1367077
TI  - Extractive bioconversions in aqueous two-phase systems.

PMID- 1367078
TI  - Solid sorbents used in extractive bioconversion processes.

PMID- 1367079
TI  - Extractive removal of product by biocatalysis.

PMID- 1367080
TI  - Bioconversions in permeabilized cells.

PMID- 1367081
TI  - Liquid-liquid extractive membrane reactors.

PMID- 1367082
TI  - Methods for removing N-terminal methionine from recombinant proteins.

PMID- 1367083
TI  - Purification of secreted recombinant proteins from Escherichia coli.
AB  - Secretion systems engineered for the expression of heterologous protein in E.
      coli provide several advantages for subsequent isolation of purified product.
      Proteins released from the periplasmic space, which represent a small fraction
      (i.e., 4-10%) of total cell protein, can readily be separated from other cellular
      proteins by centrifugation of the remaining cellular debris or cross-flow
      ultrafiltration. The starting material derived from secretion systems is
      generally of higher purity than comparable material produced from strains
      expressing cytoplasmically for systems exhibiting similar expression levels. The
      available evidence suggests that recombinant proteins derived from the periplasm
      are generally, but not always (44-46), soluble in a nonaggregated form.
      Consequently, simple purification protocols can be effectively employed for
      producing homogeneous product with a high yield. The majority of the secreted
      recombinant proteins reviewed in this chapter were purified by simple one- or two
      step chromatography procedures. High-resolution techniques such as reversed phase
      HPLC were found necessary only in cases where the secreted polypeptides were
      contaminated with proteolytic degradation variants, e.g., hirudin (51) and beta
      endorphin (22). The fact that a high level of biological activity has been shown
      to be characteristic of purified recombinant proteins secreted into the
      periplasmic space suggests the presence of a native conformation stabilized by
      the expected disulfide linkages. Intramolecular disulfide bonds most probably
      form either as the polypeptide is translocated through the cytoplasmic membrane
      into the periplasm or within the periplasmic compartment, which has a higher
      oxidation potential than that found in the cytoplasm (57). Studies performed with
      hGH (31) and muIL-2 (35) provide excellent examples of differences observed in
      protein folding and disulfide bond formation between heterologous proteins
      expressed in the cytoplasmic and periplasmic compartments. Thus, hGH and muIL-2
      extracted from the cytoplasm of E. coli have been characterized as high molecular
      weight disulfide-bonded oligomers. It is likely that oligomerization occurs as
      the polypeptides are released from the reducing environment of the cytoplasm. In
      contrast, secreted hGH and muIL-2 extracted from the periplasm of E. coli by
      osmotic shock displayed the properties of a property folded native protein with
      correct disulfide pairing. In the case of muIL-2 only a small residual fraction
      (approximately 15%) of the purified secreted protein exhibited incomplete
      oxidation of cysteine (35). Secretion of heterologous proteins into the periplasm
      prevents their exposure to the action of proteases located in the cytoplasm of E.
      coli (58). The smaller polypeptides such as somatostatin (59), IGF-1 (46), and
      hEGF (54) are known to be particularly susceptible to intracellular
      degradation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1367084
TI  - Purification of recombinant proteins from yeast.

PMID- 1367085
TI  - Production of recombinant proteins in the methylotrophic yeast Pichia pastoris.

PMID- 1367086
TI  - Purification of monoclonal antibodies.

PMID- 1367087
TI  - Engineering proteins to enable their isolation in a biologically active form.

PMID- 1367088
TI  - Recombinant DNA technology and crystallography. A new alliance in unraveling
      protein structure-function relationships.

PMID- 1367089
TI  - Purification and analysis of recombinant proteins.

PMID- 1367090
TI  - Physical and chemical cell disruption for the recovery of intracellular proteins.
AB  - There are many ways to disrupt microorganisms and plant and animal tissue.
      Selecting the best cell disruption method depends on the factors listed in Table
      6. The kind or type of cells is an important consideration. For example, some
      disruption methods which work well for animal tissue do not work at all for
      microorganisms. A guideline for the suitabiity of a given disruption method for
      some cell types is given in Table 7. The ratings in this table are not
      incontestable and, as mentioned earlier, combinations of methods can sometimes
      produce satisfactory results whereas one method alone fails. The disruptibility
      of cells can be influenced by their growth and storage history. For
      microorganisms, cells in log phase growth tend to produce thinner cell walls
      which are more easy to disrupt. This and other conditions which can influence
      microbial cell disruptiability are listed in Table 8. The cell disruption method
      selected will depend on its capability to process samples of a certain size or to
      be able to process multiple samples in a reasonable period of time. Other
      considerations are the availability, cost, and general utility of the disruption
      equipment. Thus, in a research environment the purchase of an expensive cell
      disrupter which processes a wide variety of cell types may be more easy to
      justify than a specialized disrupter. And if the long-term goal is to scale up,
      the choice of disruption methods narrow considerably. Indeed, several of the most
      successful laboratory cell disruption methods have no possibility of being scaled
      up. Despite possible scale-up difficulties, in the case of many bioactive
      recombinant products expressed at high levels in microorganisms, this concern may
      be irrelevant. Few of these products are likely to be manufactured in really
      large amounts and current laboratory scale or pilot plant scale production
      equipment may be entirely adequate. For instance, active human TNF (tissue
      necrosis factor) can be expressed in Pichia pastoris yeast at levels of 100 g/kg
      of yeast (dry weight). At this level of expression, only a few kilograms of r-DNA
      yeast needs be disrupted to meet the worldwide demand for this research material.
      Finally, the operating and energy requirements which affect the economics of the
      disruption process (batch versus continuous, disruption yield, cell fragment
      size, effect of added enzymes on downstream separation, etc.) are important
      considerations in the selection of production equipment.

PMID- 1367091
TI  - Intracellular immunization: a new strategy for producing disease-resistant
      transgenic livestock?

PMID- 1367092
TI  - Public funding of research and development: a broad picture.

PMID- 1367093
TI  - The competitive market for antiplatelets and thrombolytics: can a new entrant
      succeed?
AB  - The current lack of available antiplatelet and thrombolytic agents, the
      limitations of existing products, the possibility of value-pricing, and the sheer
      number of potential candidates for therapy all combine to produce a market with
      tremendous potential. Given these very significant incentives, it is no wonder
      that so many pharmaceutical companies have chosen to pursue research in the
      antithrombotic field.

PMID- 1367094
TI  - Applications of bacterial magnets.
AB  - Magnetic bacteria migrate along the lines of the earth's magnetic field, and
      synthesize intracellular particles of magnetite which are aligned in chains and
      enveloped by a membrane, thus forming biological magnets. Recent progress in
      techniques for isolating and culturing one strain offers hope for the large-scale
      production of bacterial magnets. Potential biotechnological and medical
      applications will exploit the ability to manipulate conjugates or cells
      incorporating the particles, whose usefulness depends on their small size and
      membrane coating.

PMID- 1367095
TI  - Studying DNA-protein interactions using NMR.
AB  - NMR spectroscopy is emerging as a powerful tool in molecular biology and
      biotechnology; one aspect of which is the use of one- and two-dimensional NMR
      methodologies to investigate the interactions of proteins with DNA. The dynamic
      and structural information which NMR can provide, on the changes in conformation
      and molecular flexibility, complements X-ray crystallography data and enables
      mechanistic models of DNA-protein interactions to be formulated.

PMID- 1367096
TI  - Biotechnology and the environment: a Birmingham perspective.

PMID- 1367097
TI  - Bio-techniques for the detection of genetic toxicity in the aquatic environment.
AB  - This article reviews the application of sensitive biotechniques in the detection
      of DNA damage within the aquatic environment as "early warning" indicators of
      pollution-related genetic toxicity. Bacterial mutagenicity assays have played an
      important role both in the discovery of mutagens and in the analysis of the
      ability of aquatic organisms to convert inert substances to reactive genotoxic
      products. Genetic damage in aquatic species treated with carcinogens has been
      detected by analysis of DNA adducts, induction of DNA repair, DNA strand breakage
      and formation of chromosomal aberrations and sister chromatid exchanges. Little
      information is available on pollution-related DNA damage resulting from field
      exposure. A 32P-postlabelling technique for the sensitive detection of DNA
      adducts is a promising development towards this aim and the analysis of changes
      in oncogene nucleotide sequence in tumour tissue is considered an important
      future direction.

PMID- 1367098
TI  - Electrically controlled proliferation of human carcinoma cells cultured on the
      surface of an electrode.
AB  - Human carcinoma cells, MKN45, were cultured on the surface of a metal-coated
      plastic plate electrode the potential of which was controlled. The proliferation
      rate and cell morphology were altered depending on the applied potential. Cell
      proliferation was halted in the potential range above 0.4 V vs. Ag/AgCl, although
      cells started to proliferate again when the applied potential was shifted from
      0.4 V to 0.1 V vs. Ag/AgCl. Fluorescence probe studies indicated that the
      fluidity of plasma membrane decreased in association with halting of cell
      proliferation. These results suggest that electrical stimulation causes cells to
      temporarily halt proliferation, and that cell proliferation was reversibly
      controlled by electrode potential. The mechanism is interpreted in relation to
      the change of plasma membrane structure represented by membrane fluidity.

PMID- 1367099
TI  - Examination of serum and bovine serum albumin as shear protective agents in
      agitated cultures of hybridoma cells.
AB  - A murine hybridoma cell line (167.4G5.3) was cultured in batch mode using IMDM
      containing different serum concentrations and bovine serum albumin (BSA). Cell
      growth and death, metabolism and antibody production were studied in these
      cultures. The cells were more susceptible to shear in the stationary and in the
      decline phase of growth as evidenced by higher death rates. Cell growth was best
      at high serum concentrations with high specific growth and low specific death
      rates. When BSA was used instead of serum in IMDM, no protective effect was
      observed. Cell metabolism and monoclonal antibody production rates were not
      influenced by the level of serum or by BSA. The use of serum in commercial serum
      free media (OPTI-MEM) also resulted in no change in both growth and death rates.

PMID- 1367100
TI  - The effect of the partition locus on plasmid stability and expression of a
      prolonged chemostat culture.
AB  - The stability, copy number, and gene expression of the pBR322 plasmid containing
      the par-locus under prolonged cultivation were studied. In the initial stage of
      the experiment it was observed that the par-locus had a stabilization effect on
      plasmid maintenance. This observation was consistent with previously reported
      results. However, after approximately 225 h, a mixed population of plasmid
      containing and plasmid-free cells appeared. The mixed culture was stably
      maintained for approximately 200 h. In addition, the relative plasmid copy number
      showed an increase as compared to the par- culture. After 100 h the copy number
      decreased, reached a minimum, then stabilized. The beta-lactamase activity, was
      not significantly affected by the par-locus.

PMID- 1367101
TI  - On-line determination of glucose in biotechnological processes: comparison
      between FIA and an in situ enzyme electrode.
AB  - Two different analysis techniques for on-line monitoring of glucose in
      biotechnological processes have been tested: an in situ enzyme electrode and a
      flow injection analysis system (FIA). The measuring ranges, detection limits,
      response times and the reliabilities of each system have been compared during
      monitoring of batch and continuous cultures of Saccharomyces cerevisiae.

PMID- 1367102
TI  - On-line determination of glucose concentration throughout animal cell cultures
      based on chemiluminescent detection of hydrogen peroxide coupled with flow
      injection analysis.
AB  - A flow-injection analysis (FIA) system for the on-line determination of glucose
      in animal cell cultures is described. The system is based on immobilized glucose
      oxidase (GOD). The hydrogen peroxide generated in the enzyme reaction is
      determined via a highly sensitive chemiluminescent reaction with luminol. Based
      on the measurement of the maximum emitted light intensity, the system was able to
      analyse hydrogen peroxide over the concentration range of 10(-7) to 10(-2) M. For
      glucose determination, the system has a linear range of 10(-5) to 5 x 10(-2) M
      glucose, with an r.s.d. of 3% at the 1 mM level (5 measurements). The influence
      of luminol and buffer concentrations, pH and temperature on the chemiluminescent
      reaction were investigated. The enzyme reactor used was stable for more than 4
      weeks in continuous operation, and it was possible to analyse up to 20 samples
      per h. The system has been successfully applied to on-line monitoring of glucose
      concentration during an animal cell culture, designed for the production of human
      antithrombin III factor. Results obtained with the FIA system were compared with
      off-line results, obtained with a Yellow Springs Instrument Company Model 27
      (YSI).

PMID- 1367103
TI  - Influence of carnitine on the growth and productivity of murine hybridoma cells.

PMID- 1367104
TI  - Preventing a biological arms race: a conference report.

PMID- 1367105
TI  - The patenting of transgenic animals--will it matter at the end of the day?

PMID- 1367106
TI  - Development of guidelines for small scale genetic manipulation work.
AB  - The Genetic Manipulation Advisory Committee (GMAC) is the national body which
      reviews research and development work in Australia using genetic manipulation
      technologies. It supersedes and continues the work of the Recombinant DNA
      Monitoring Committee (RDMC). GMAC has recently drafted new guidelines for small
      scale laboratory work. The difference between these guidelines and the ones they
      have replaced is the broadening of the scope of work to be monitored, from
      recombinant DNA work to other genetic technologies which may also produce new
      combinations of inheritable genetic material. Experience from assessing proposals
      over the life of the RDMC and a previous Academy of Science committee enabled the
      GMAC Scientific Sub-committee to be more specific about the experiments it wanted
      to assess before they can begin, and those which could be safely exempted from
      the guidelines.

PMID- 1367107
TI  - International trends in biotechnology regulation: the implications for developing
      countries.
AB  - Evolutionary processes have demonstrated that genetic mutations can, over time,
      produce a complete restructuring of the previous ecological order. The capacity
      of biotechnology to manipulate and transform genetic material at a far greater
      rate than nature is capable of suggests that careful consideration should be
      given to effectively controlling these technologies. This paper examines the
      underlying technical and philosophical concerns and arguments which underpin the
      development of appropriate regulations for biotechnology. The regulatory
      frameworks which have been set in place around the world are reviewed.
      Modifications which are being introduced in the light of increasing practical
      experience and in response to changing societal pressures are discussed.
      Potential negative impacts of biotechnology on developing countries are
      specifically addressed. A case is made for co-ordinated international efforts to
      develop consistent and uniform legislation for the safe and environmentally
      beneficial application of biotechnology on a more equitable global basis.

PMID- 1367108
TI  - Diagnostics--international state and development in the 1990s.

PMID- 1367109
TI  - Opportunistic infections in AIDS and their diagnosis.
AB  - AIDS patients are susceptible to a variety of infections from microorganisms as a
      result of their immunosuppressed condition. These infections are mainly
      responsible for the morbidity and mortality in these patients. The organisms
      responsible include protozoa, bacteria, fungi and viruses. Their presence may be
      a result of reactivation of latent or previous infection, or exposure to
      opportunistic agents. The seriousness of the patients' condition makes rapid and
      early diagnosis imperative so that appropriate treatment can be instituted.
      Methods of diagnosis including more recent technology are discussed.

PMID- 1367110
TI  - Addressing changing technology in diagnostics: the Bioclone elegance system.

PMID- 1367111
TI  - Production of recombinant products in yeasts: a review.
AB  - This paper reviews the use of yeasts to produce heterologous proteins via the
      development of transformation systems. The ability to genetically engineer yeast
      cells has many advantages over prokaryotic systems. Yeasts are already well
      established in fermentation procedures, are able to secrete glycosylated and
      modified proteins to render the proteins biologically active, and yeasts do not
      secrete toxic chemicals. With the techniques available it is possible to explore
      yeasts as hosts for the expression and secretion of commercially-useful proteins.

PMID- 1367112
TI  - Biotechnology: the science, the business and the bull. Key address to the ninth
      Australian biotechnology conference.

PMID- 1367113
TI  - Bioquest Ltd.

PMID- 1367114
TI  - Cell cycle analysis in flow cytometry: use of BrdU labelling and side scatter for
      the detection of the different cell cycle phases.
AB  - Cell cycle analysis in flow cytometry is based on the incorporation of labelled
      precursors in DNA. The use of BrdU versus SSC, in which side scatter substitutes
      PI fluorescence, has proved to be useful also for the distinction between G2 and
      Mitotic cells. Mitoses often produce an SSC decrease due to the morphological
      changes that happen in the nucleus during this phase of cell cycle. Moreover, DNA
      accessibility to PI varies during mitosis, as well. However, most of these
      variations, detectable by flow cytometry appear to be basically dependent on the
      cell line used.

PMID- 1367115
TI  - Image analysis techniques. The problem of the quantitative evaluation of the
      chromatin ultrastructure.

PMID- 1367116
TI  - Selective modulation with liposomes containing Der.P1 labelled with monoclonal
      antibodies.

PMID- 1367117
TI  - Long-term culture of human LAK cells.

PMID- 1367118
TI  - Use of monoclonal antibodies in solid tumors diagnosis: the endometrial
      carcinoma.

PMID- 1367119
TI  - Intracellular immunization: expression of antibody domains in the cytoplasm and
      in the nucleus of mammalian cells.

PMID- 1367121
TI  - Methylation state of the human HLA-DR alpha gene in transgenic mice.

PMID- 1367120
TI  - Alternative methods in toxicology tests: in vitro toxicity.
AB  - Toxicity testing is required for new chemicals being introduced onto the market.
      The use of animals in evaluating chemical safety is costly and time consuming.
      Furthermore, there is the ethical need to develop alternative methods to reduce
      the required number of animals. The new in vitro assays offer numerous advantages
      such as speed, reproducibility and control of test conditions, and increased
      sensitivity. Although the dermal irritation assays might be substituted by the in
      vitro tests in the near future (Duffy, 1989), much work is required to evaluate
      organ toxicity with in vitro methods. We present data regarding the use of
      Balb/3T3 mice fibroblasts and primary rat hepatocytes as test systems for in
      vitro toxicity. The end-points we have analysed are total protein content, dye
      accumulation in lysosomes, reductase mitochondrial activity, intracellular
      content and leakage of enzymes into the medium.

PMID- 1367122
TI  - Cell metabolism measurements in culture via microelectronic biosensors.
AB  - Silicon-based H(+)-sensitive biosensors in proximity to a cell population detect
      variations in cell metabolism via local measurements of changes in pH. The
      feasibility of this approach is shown in the case of ISFET devices.

PMID- 1367123
TI  - Characterization of a subfamily of zinc finger genes expressed in human
      hematopoietic cell lines.
AB  - We isolated by low stringency screening of a human erythroleukemia cDNA library
      (K562) 45 independent clones hybridizing to a Kruppel-like (HF.10) zinc finger
      cDNA. The expression of 15 such cDNAs in human hematopoietic cell lines was
      investigated. Preliminary sequence analysis of the zinc finger motifs in these
      cDNAs indicate that they belong to a subclass of the Cys-Cys/His-His motif,
      showing the highest homology to the Wilm's tumor and EGR1, EGR2 cDNAs.

PMID- 1367124
TI  - Fluorimetric approaches to the study of calcium transients in living cells.
AB  - This paper is a short review of the fluorimetric methods used to measure
      intracellular free Ca++ concentration in living cells. The availability of
      fluorescent probes has greatly contributed to the understanding of the mechanisms
      responsible for the cellular homeostasis of this second messenger. Data can be
      collected from populations of cells by spectrofluorimetry or from small groups or
      single cells by spectromicroscopy. Finally the fluorescent images can be captured
      by a high sensitivity camera, digitally processed and convert in Ca++ images of
      the cell. The technique allows recognition of differences in [Ca++]i transients
      among adjacent cells in a same field or in different regions of a cell and
      greatly contributes to the identification of the cellular mechanisms modulating
      [Ca++]i.

PMID- 1367125
TI  - Office of Naval Research lecture. Antibiotics and the search for new principles.

PMID- 1367126
TI  - Expression of polyketide biosynthesis and regulatory genes in heterologous
      streptomycetes.
AB  - There are now several examples showing that hybrid secondary metabolites can be
      produced as a result of interspecies cloning of antibiotic biosynthesis genes in
      streptomycetes. This paper reviews examples of hybrid secondary metabolite
      production, and examines the underlying biochemical and regulatory principles
      leading to the formation of hybrid anthraquinones by recombinant anthracycline
      producing streptomycetes carrying actinorhodin biosynthesis genes. An
      anthraquinone, aloesaponarin II, was produced by cloning the actI, actIII, actIV,
      and actVII genes (pANT12) of actinorhodin biosynthesis pathway from Streptomyces
      coelicolor in anthracycline producing streptomycetes. Streptomyces galilaeus
      strains 31 133 and 31 671, aclacinomycin and 2-hydroxyaklavinone producers,
      respectively, formed aloesaponarin II as their major polyketide product when
      transformed with pANT12. Subcloning experiments indicated that a 2.8-kb XhoI
      fragment containing only the actI and actVII loci was necessary for aloesaponarin
      II biosynthesis by S. galilaeus 31 133. When S. galilaeus 31 671 was transformed
      with the actI, actVII, and actIV genes, however, the recombinant strain produced
      two novel anthraquinones, desoxyerythrolaccin and 1-O-methyldesoxyerythrolaccin.
      When S. galilaeus 31 671 was transformed with only the intact actIII gene
      (pANT45), aklavinone was formed exclusively. These experiments indicate a
      function for the actIII gene, which is the reduction of the keto group at C-9
      from the carboxyl terminus of the assembled polyketide to the corresponding
      secondary alcohol. The effects of three regulatory loci, dauG, dnrR1, and asaA,
      on the production of natural and hybrid polyketides were also shown.

PMID- 1367127
TI  - Biological activity of a transforming growth factor-alpha--Pseudomonas exotoxin
      fusion protein in vitro and in vivo.
AB  - Transforming growth factor-alpha (TGF alpha)-pseudomonas exotoxin-40 (PE40) is a
      chimeric protein consisting of an N-terminal TGF alpha domain fused to a C
      terminal 40-kDa segment of the pseudomonas exotoxin A protein. TGF alpha-PE40
      exhibits the receptor binding activity of TGF alpha and the cell killing activity
      of PE40. In the current study, we report that a modified TGF alpha-PE40
      derivative significantly prolongs the survival of nude mice bearing tumors
      derived from cell lines which express the epidermal growth factor receptor
      (EGFR). In addition, the therapeutic benefit of this protein is mediated by
      specific binding to the EGF receptor. These results indicate that a therapeutic
      window exists in vivo for the use of some growth factor--toxin fusion proteins as
      anticancer agents.

PMID- 1367128
TI  - Medical biotechnology: a brief historical survey.

PMID- 1367129
TI  - Fermenters for prokaryotic cells.

PMID- 1367130
TI  - Bioreactor and process design for large-scale mammalian cell culture
      manufacturing.
AB  - Good Manufacturing Practice for pharmaceuticals requires that the manufacturing
      processes be controlled and reproducible. The biological nature of cell culture
      based processes lends them an inherently higher variability than is generally
      found for processes involving production of defined chemical entities. As one
      regulatory body has pointed out, this places a greater emphasis on in-process
      controls and adherence to GMPs in the manufacture of cell culture products.
      Design of bioreactors and associated process control systems is a key element in
      the successful implementation of a commercial-scale cell culture manufacturing
      process capable of meeting such high standards. It should be noted that reactor
      and control system designs for animal cell culture are still very much in a state
      of evolution from the modified bacterial fermentation systems that currently
      predominate, and it is difficult to predict how design strategies may change in
      the coming years. Having said this, however, it should be clear from the
      information presented here that satisfactory processes can be devised today using
      proven equipment configurations such as the stirred-tank reactor.

PMID- 1367131
TI  - Automatic control systems.

PMID- 1367132
TI  - Fermentation processes for prokaryotic cells.

PMID- 1367134
TI  - Industrial scale mammalian cell culture.

PMID- 1367133
TI  - Recombinant yeast as a production system in biotechnology.

PMID- 1367135
TI  - Production-scale purification processes.

PMID- 1367137
TI  - Food and Drug Administration inspection and licensing of manufacturing
      facilities.

PMID- 1367136
TI  - Characterization of proteins from recombinant DNA manufacture.

PMID- 1367138
TI  - Scientific and regulatory considerations in the development of human growth
      factors.

PMID- 1367139
TI  - Industry's experience with worldwide regulation of biotechnology products.

PMID- 1367140
TI  - Culturing a biotech company in a regulatory medium.

PMID- 1367141
TI  - Fungi as bioprocessing systems for the production of pharmaceutically important
      proteins.

PMID- 1367142
TI  - Baculovirus expression systems and insect cells.

PMID- 1367143
TI  - Second-generation products: antibiotics.
AB  - There has been outstanding progress in gene cloning from microorganisms producing
      useful antibiotics. Especially noteworthy is the cloning of a gene for
      cephalosporin biosynthesis that, with increased copy number, helps to overcome a
      rate-limiting step in biosynthesis. Although this technology is often fraught
      with unexpected difficulties, not the least of which is gene expression, yield
      improvement is a practical application with clear financial benefits to the
      pharmaceutical industry. Although access to cloned genes for antibiotic
      biosynthesis is becoming common, expression of the cloned genes in a manner such
      that yield improvement is achieved is a challenge that will be exciting and
      beneficial in years to come. Heterologous (interspecies) gene expression in
      antibiotic-producing microorganisms, particularly the actinomycetes, must be
      successful if hybrid antibiotics are to be produced. Currently, there are no
      documented examples of heterologous gene cloning to yield a hybrid antibiotic of
      utility. Even though a hybrid antibiotic structure has been reported as a result
      of heterologous gene cloning, the antibiotic is not clinically useful, and the
      two species used in the experiments are closely related. Although technological
      advances have enabled successful gene cloning, insufficient attention has been
      given to the issue of gene expression, particularly heterologous gene expression.
      The need to develop heterologous gene expression systems is urgent. Until this is
      done, the inability to express cloned antibiotic biosynthesis genes in
      heterologous hosts could be a barrier to the generation of useful hybrid
      antibiotics. The potential for a wide array of new antibiotic compounds that
      could be generated by gene-cloning technology is vast. At least until the
      limitations of heterologous gene expression are overcome, the best available
      screening technology (including molecular and immunological screens) and
      chemistry might best serve as the most prolific means of discovering useful new
      antibiotics for agriculture and medicine.

PMID- 1367144
TI  - Novel approaches for the production of biotechnologically derived vaccines of the
      future.

PMID- 1367145
TI  - Advances toward somatic cell gene therapy.

PMID- 1367146
TI  - Harmonization of biotechnological regulations in the European Community.

PMID- 1367147
TI  - The Japanese perspective regarding regulatory concerns for biotechnology drugs
      and their scientific basis.

PMID- 1367148
TI  - Regulatory evaluation of biotechnology drugs: current trends in the United
      States.

PMID- 1367149
TI  - A scenario for the future: biotechnology and pharmacogenesis.

PMID- 1367150
TI  - A compilation of government regulation of biotechnology.

PMID- 1367151
TI  - The preparation and validation of stock cultures of mammalian cells.
AB  - The utilization of continuous cell substrates is now widely accepted for the
      production of biologics. As part of the evaluation and licensing process of these
      products, the regulatory agencies are requiring extensive validation of the
      production system. That production system begins with the validation or
      qualification of a defined cell bank. This includes the validation of the
      stability cells at both the genetic and biochemical levels during cell culture
      production. Process validation plus cell bank validation provide the necessary
      assurance that the final product will be free of contaminating viruses and other
      adventitious agents. A combination of cell bank characterization and product
      characterization (peptide mapping or amino acid sequencing, or a combination
      thereof) will also demonstrate the stability of the production process. The
      validation of a cell bank for adventitious agents and cell line stability will
      not, in itself, ensure that the product is sterile and stable. However, cell bank
      validation is critical for demonstrating the safety of a product when combined
      with both process validation and end-product testing.

PMID- 1367152
TI  - Genetic and molecular studies to certify seed pools and production fermentations
      of industrial Escherichia coli strains.

PMID- 1367153
TI  - Cultivation, characterization and modulation of rat thymic non-lymphoid cells in
      vitro.
AB  - Thymic fragments of young adult rats were cultivated in vitro using an explant
      technique. Two weeks later, non-lymphoid cells were characterized by enzyme
      cytochemistry and immuno-cytochemistry. Based on cytomorphological criteria and
      cell-specific markers approximately 95% of cells were classified into 3 main
      types: epithelial cells, macrophages and fibroblasts. The effect of dexamethasone
      and amphotericin B, known modulators of cell growth in culture was also studied.
      Quantitative analysis showed that amphotericin B inhibited proliferation of
      macrophages and epithelial cells, while dexamethasone suppressed proliferation of
      fibroblasts and promoted growth of epithelial cells.

PMID- 1367154
TI  - Combination of culture on collagen gels and glucose starvation for cloning human
      colon cancer cells. Obtention of clones exhibiting different patterns of
      enterocytic differentiation.
AB  - Glucose starvation has been widely used to select differentiated subpopulations
      from the heterogenous human colon cancer cell line HT29. We observed that the
      important cell loss elicited by culturing these cells in glucose-free medium
      could be limited when type I collagen gel was used as substratum instead of
      conventional plastic support. We took advantage of this property to develop a new
      protocol, which combined glucose starvation and culture on collagen gels, for
      cloning HT29 cells. Using this procedure we have isolated four clones that were
      characterized on the basis of morphological (optical and transmission electron
      microscopy), electrophysiological (determination of transepithelial electrical
      parameters) and biochemical (detection of villin, sucrase-isomaltase and
      carcinoembryonic antigen) criteria. These four clones expressed different
      patterns of enterocytic differentiation regarding to these criteria. These
      results confirmed the heterogeneity of the HT29 cell line. One of these clones,
      HT29-A7, which displayed numerous intercellular cysts that disappeared at
      confluency, appears as a complementary model in the study of epithelial
      biogenesis.

PMID- 1367155
TI  - Improved microscopic observation of mammalian cells on microcarriers by
      fluorescent staining.
AB  - Many microcarriers used for the cultivation of animal cells do not allow for
      convenient microscopic observation of cell morphology and viability due to their
      optical properties. Using fluorescent viable stain combining fluorescein
      diacetate and ethidium bromide, we observed the distribution, morphology and
      viability of cells on various microcarriers.

PMID- 1367156
TI  - Characterization of a new continuous cell line from the flood water mosquito,
      Aedes vexans.
AB  - A new cell line, UM-AVE1, was established from embryos of the mosquito Aedes
      vexans. Banding patterns for the isozymes lactate dehydrogenase (LDH), malate
      dehydrogenase (MDH), isocitrate dehydrogenase (IDH), xanthine dehydrogenase
      (XDH), and esterases were compared with those of larval Aedes vexans tissues as
      well as those of four other mosquito cell lines and one moth cell line. Karyotype
      analyses confirmed that the dipteran cell lines were not contaminated with
      lepidopteran cells, because in all mosquito lines the modal number of chromosomes
      was 6 (= 2n) or 7. Isozyme electrophoresis established a specific profile for
      each cell line. Two isozymes present in UM-AVE1 (LDH, IDH) were not detected in
      larvae; this could be a reflection of the different stages used for cell line
      isolation and enzyme analysis, or lability of sample preparations. It is
      significant that extracts from UM-AVE1 cells and Aedes vexans larvae had an
      identical double band for XDH, while all other cell lines examined exhibited only
      a single band.

PMID- 1367158
TI  - Influence of inoculum age on hybridoma culture kinetics.
AB  - To determine the influence of the inoculum age on the kinetics of hybridoma
      growth and metabolism, spinner flasks have been inoculated with cells previously
      propagated in T flasks for 43, 52, 62 and 71 hr respectively. Increasing the age
      of the inoculum is found to result in a longer lag phase, in a lower maximum
      specific growth rate and in a reduced maximal cell density. During the growth
      phase specific rates of glucose and glutamine uptake and of ammonia and lactate
      production are similar. However, with the older inoculum, much higher metabolic
      activities are observed during the lag phase. The production of antibodies is
      delayed with increasing inoculum age, but the final antibody concentrations are
      similar, which indicates a higher specific antibody production rate when
      inoculating with older cells.

PMID- 1367157
TI  - Methods for improving tissue culture of human tracheo-bronchial epithelium
      obtained at autopsy.
AB  - Human tracheo-bronchial epithelium obtained from autopsy, surgery, and organ
      donation will have areas of both viable and non-viable cells. It is important in
      the initial establishment of epithelial explant and cell cultures that injured,
      non-viable mucosal epithelium not be used for the cultures. Autopsy cases
      selected for culture should initially be chosen on the basis of a shorter post
      mortem interval and cause of death in order to increase the rate of successful
      culture. Staining the epithelium with the vital dye, trypan blue, in combination
      with phase contrast microscopy of the bronchial tissues will further identify
      those areas of the mucosa that are enriched for viable cells. The dead, non
      viable areas are trypan blue positive, while the viable areas are clear and have
      foci of beating, motile cilia. Treatment of the mucosal tissue with mucolytic
      agents to remove cell debris, dead cells, and microbes trapped in the mucus
      material will further improve the chances for successful culture. Human tracheo
      bronchial epithelium, although non-sterile and often injured at time zero for
      numerous reasons, can effectively be used in vitro pathophysiology studies.

PMID- 1367159
TI  - Primary culture and cryopreservation of mouse astrocytes under serum-free
      conditions.
AB  - The methods of primary culture and cryopreservation of mouse astrocytes under
      serum-free conditions were examined. Cerebra from newborn C3H/He mice were
      employed as the source of astrocytes. The cultured cells were able to grow in a
      serum-free, chemically defined medium containing transferrin, hydrocortisone,
      biotin, sodium selenite, insulin, fibroblast growth factor and epidermal growth
      factor. After the culture was maintained in the medium for 3 weeks, purity was
      assessed using immunofluorescence staining. The great majority of the cells
      (greater than 98%) contained glial fibrillary acidic protein and S-100 protein
      which are cell markers of astrocytes. To cryopreserve the enriched astrocytes
      under serum-free conditions, various cryoprotectants were examined. The
      combination of 10% dimethylsulfoxide and 0.1% methylcellulose gave the highest
      survival rate. These methods of primary culture and cryopreservation will be
      useful in physiological and biochemical studies which require mouse astrocytes.

PMID- 1367160
TI  - Agitation rate effects on plasmid stability in immobilized and free-cell
      continuous cultures of recombinant E. coli.
AB  - Escherichia coli B/pTG201 recombinant cells were immobilized by entrapment in a
      carrageenan gel and cultivated in nonselective media to investigate the effect of
      agitation rate on plasmid stability, biomass concentration, and enzyme
      productivity. These parameters were studied in continuous cultures for free and
      immobilized cells, respectively. Immobilized recombinant cells exhibit an
      increase in the stability of the plasmid pTG201 compared to free cells, even
      under conditions where the tendency of plasmid stability for free cells decreased
      generally more rapidly under a higher agitation rate. Intensive agitation,
      resulting also in a strong shear stress, greatly reduced cell concentration
      within gel beads throughout the course of growth. Higher enzyme expression of
      catechol 2-3, dioxygenase was also obtained in leaked cells due to better
      maintenance of plasmid stability and higher plasmid copy number with regard to
      free cells. Enzyme productivity of leaked and free cells in minimal medium
      decreased with the increase in agitation rate, due to decreased plasmid
      stability; however, in LB medium, it increased in the presence of higher
      agitation rate related to important cell concentration.

PMID- 1367161
TI  - Water activity as a key parameter of synthesis reactions: the example of lipase
      in biphasic (liquid/solid) media.
AB  - Ester synthesis catalyzed by Candida cylindracea lipase (triacylglycerol
      acylhydrolase, EC 3.1.1.3) was investigated in solid/liquid biphasic media
      containing the enzyme preparation and reactants without addition of organic
      solvents not participating in the reaction. Although the effects of water on
      enzyme kinetics have been abundantly studied in nearly anhydrous media, reactions
      in which water is produced have not been investigated. The effect of water
      produced by the reaction itself on the enzymatic activity was studied. The
      dispersion of water in a shaken, nearly anhydrous medium was shown to be
      responsible for the lack of activity of the enzyme. In contrast, when slowly
      shaken, the enzyme was fully activated by the water furnished as a product of the
      reaction. However, when experiments were performed in a two-phase aqueous/organic
      system with previously solubilized enzyme in water, the enzyme activity was
      increased by shaking and was of the same order of magnitude as in nearly
      anhydrous media. Under low water activity conditions, a powerful agitation can
      lead to slower reaction rate, because water, a product of esterification, is not
      retained in the microenvironment of the enzyme to activate it. The activation
      effect of water produced by the reaction was clearly shown using enzyme
      preparations shaken in an anhydrous medium and previously equilibrated at low
      water activities (aw = 0.13 and 0.69). This activation did not occur for an
      enzyme preparation equilibrated at high aw (0.89) or for a preparation gently
      shaken in a water-saturated medium. The lag time preceding activation of the
      enzyme increased with the extent of enzyme dehydration.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1367162
TI  - Production of acid proteinases by Humicola lutea mycelium immobilized in
      polyurethane sponge.
AB  - Humicola lutea 120-5 spores were entrapped in polyurethane sponge cubes and were
      cultivated inside the carrier to form an immobilized mycelium further used for
      production of acid proteinases in batch mode. A carrier--spore suspension ratio
      of 10:0.5 (wt) should be used to obtain optimal results. The polyurethane sponge
      immobilized mycelium could be applied repeatedly, the enzyme activity secreted
      during the first 10 cycles being about the same as that produced by free cells.
      The advantages of immobilizing fungal cells by germinating conidia entrapped
      inside the supporting material are discussed.

PMID- 1367163
TI  - Concanavalin A: a useful ligand for glycoenzyme immobilization--a review.
AB  - Concanavalin A is finding increasing applications as a useful ligand in
      glycoenzyme immobilization. An attempt therefore, has been made to summarize the
      work available in the area. Glycoenzymes that are recalcitrant to immobilization
      procedures involving covalent coupling to solid supports can be immobilized in
      high yields by binding to matrices precoupled with concanavalin A. In addition,
      glycoenzymes associated with concanavalin A matrices usually exhibit high
      retention of activity and enhanced stability against various forms of
      inactivation. Binding of the glycoenzymes on the concanavalin A supports, being
      noncovalent, can be reversed by incubating the preparation with a high
      concentration of sugars/glycosides or at acidic pH. The association can be,
      however, rendered covalent by crosslinking the preparations with bifunctional
      reagents like glutaraldehyde. Crosslinking may be accompanied by further increase
      in stability, albeit at the expense of the loss of some enzyme activity. Several
      laboratory-size reactors containing concanavalin A matrix-bound glycoenzyme have
      been successfully operated for reasonably long durations with only small losses
      in catalytic activity. Insoluble glycoenzyme preparation can also be obtained by
      precipitating them from solution as concanavalin A complexes. Such complexes have
      small particle dimensions but can be successfully used in column reactors after a
      subsequent immobilization step. Insoluble concanavalin A-flocculates containing
      various microorganisms and glycoenzymes that successfully carry out multistep
      transformations have also been obtained by several investigators.

PMID- 1367164
TI  - Activity and distribution of urease following microencapsulation within polyamide
      membranes.
AB  - Urease was microencapsulated by forming a semipermeable polyamide membrane around
      aqueous microdroplets (266 microns mean diameter) containing the soluble enzyme.
      The yield of the interfacial polymerization technique, determined
      spectrophotometrically, was 83% of the original enzyme on a mass basis, resulting
      in a final intracapsular urease concentration of 62.3 mg ml-1 or 0.1 mM. Similar
      absorption spectra of broken and intact microcapsules suggested that
      spectrophotometry may be applied in performing direct studies on the intact
      microcapsules. The high activity yield of urease microcapsules relative to the
      mass of entrapped enzyme (92.5%) indicated minimal effects of mass transfer
      limitation. The mass of active urease incorporated into the nylon membrane
      represented 6% of the encapsulated enzyme activity. The soluble intracapsular
      enzyme fraction (94%) was released into solution upon rupture of the membrane. A
      complete mass and activity balance of the encapsulated enzyme was achieved.

PMID- 1367165
TI  - Aminopropylsilane treatment for the surface of porous glasses suitable for enzyme
      immobilisation.
AB  - During silylation of porous glass with 3-aminopropyltriethoxysilane, the
      properties of the carrier affected the concentration of bound amino groups, the
      formation of aminopolysiloxane mono- or multilayer on the surface, and the
      hydrolytic stability of the layer formed. The influence of the carrier depended
      on the specific surface area and the size of pores. In contrast to silylation
      performed in organic solvents, in aqueous solutions a monolayer of
      aminopolysiloxane of high hydrolytic stability was formed on the surface of
      porous glass. Tetraethoxysilane modification of porous glass prior to silylation
      with aminosilane yields carriers of increased hydrolytic stability. Glucoamylase
      immobilised on carriers, that were modified in aqueous solutions, exhibit higher
      enzymatic activity.

PMID- 1367166
TI  - Reaction rates for the production of selected hormones by solid-phase synthesis.
AB  - Reaction rates have been measured for the production of selected bradykinins,
      angiotensins, and endorphins by solid-phase synthesis. Reactor liquid
      concentrations are monitored by using a UV detector and flow cell.
      Experimentation has been limited to low excesses of the t-Boc amino symmetrical
      anhydride. More than 500 attachments have been monitored. Most data obtained from
      resins with 1% cross-linking show second-order behavior with reaction rate
      constants between 0.5 and 8 L/(mol.s). The reaction rate is affected by chemical
      structures of both the attached amino symmetrical anhydride and the anchored
      amino terminus on the peptide fragment. Increasing reaction temperature and
      initial solution concentrations promotes reaction rate. The structure of the
      polymer support affects not only the reaction rate but also the observed reaction
      kinetics.

PMID- 1367167
TI  - Solvent selection strategies for extractive biocatalysis.
AB  - This report follows the development of systematic solvent screening strategies
      for the identification of superior pure solvents and introduces techniques for
      the identification of effective coextractants. Specifically, methods to predict
      the biocompatibility and extractant capability of solvents are discussed.
      Biocompatibility is predicted by using heuristic data or the correlations between
      bioactivity and the logarithm of the partition coefficient of the solvent or the
      concentration of solvent in the cell membrane. A computer program, known as the
      extractant screening program or ESP, has been developed to effectively predict
      the behavior of virtually any product in any solvent/aqueous system. It is
      demonstrated that a biocompatible yet poor solvent can be mixed with a toxic
      solvent that has better extractant properties to yield a mixture with improved
      solvent characteristics that is still biocompatible. The fact that solvents do
      not mix in an ideal manner is exploited by using ESP to identify solvent mixtures
      that are still biocompatible at relatively high concentrations of toxic solvent.

PMID- 1367168
TI  - Enzyme engineering for nonaqueous solvents. II. Additive effects of mutations on
      the stability and activity of subtilisin E in polar organic media.
AB  - Single amino acid substitutions increase the activity and stability of subtilisin
      E in mixtures of organic solvents and water, and the effects of these mutations
      are additive. A variant of subtilisin E that exhibits higher activity in mixtures
      of dimethylformamide (DMF) and water (Q103R) was created by random mutagenesis
      combined with screening for improved activity (K. Chen and F. H. Arnold, in
      preparation). Another mutation, N218S, known to improve both the activity and
      stability of subtilisin BPN', also improves the activity and stability of
      subtilisin E in the presence of DMF. The effects of the two substitutions on
      transition-state stabilization are additive. Furthermore, the Q103R mutation that
      improves activity has no deleterious effect on subtilisin stability. The double
      mutant Q103R+N218S is 10 times more active than the wild-type enzyme in 20% (v/v)
      DMF and twice as stable in 40% DMF. Although the effects of single mutations can
      be impressive, a practical strategy for engineering enzymes that function in
      nonaqueous solvents will most likely require multiple changes in the amino acid
      sequence. These results demonstrate the excellent potential for engineering
      nonaqueous-solvent-compatible enzymes.

PMID- 1367169
TI  - Microscopic visualization of insect cell-bubble interactions. I: Rising bubbles,
      air-medium interface, and the foam layer.
AB  - Through the use of microscopic, high-speed video technology, the interactions of
      two suspended insect cell lines, Trichoplusia ni (TN-368) and Spodoptera
      frugiperda (SF-9), with air and oxygen bubbles were studied. Events such as cell
      bubble attachment, cell-bubble collision, cell transport into the foam layer, and
      trapping of cells in the foam layer are presented and discussed. Based on these
      observations and those in a companion paper (Chalmers, J. J.; Bavarian, F.
      Biotechnol. Prog. 1991, following paper in this issue) and the experimental and
      theoretical work of other researchers, several mechanisms of cell damage as a
      result of sparging are presented.

PMID- 1367170
TI  - Microscopic visualization of insect cell-bubble interactions. II: The bubble film
      and bubble rupture.
AB  - In this paper, the second in the series, the use of a microscopic, high-speed
      video system to study the interactions of two suspended insect cells strains,
      Trichoplusia ni (TN-368) and Spodoptera frugiperda (SF-9), with rupturing bubbles
      is reported. Events such as the adsorption of cells onto the bubble film and the
      mechanism of bubble rupture were observed. On the basis of these observations and
      the experimental and theoretical work of other researchers on bubble rupture and
      cell death as a result of sparging, it is proposed that cells are killed by the
      rapid acceleration of the bubble film after rupture and the high levels of shear
      stress in the boundary layer flow associated with bubble jet formation.

PMID- 1367171
TI  - Elution conditions and degradation mechanisms in long-term immunoadsorbent use.
AB  - The limited life of immunoadsorbents used for the large-scale purification of
      biological macromolecules poses a significant limitation to the more widespread
      application of this technology. In this study, the binding activity of a
      monoclonal antibody (MAb) to bovine serum albumin (BSA) was measured as a
      function of pH, ionic strength, and varying concentrations of KSCN, ethylene
      glycol, or DMSO. Low pH (2.5) and 3 M KSCN each reduced the antibody binding
      constant below 6 x 10(5) L/mol, meeting criteria derived from a simple
      chromatographic model for identifying effective eluents. A panel of six MAb to
      BSA was exposed repeatedly to adsorption conditions and the two eluents. Four MAb
      lost less than 50% of their initial binding capacity over 100 cycles. The other
      two lost 75% of their initial capacity. One MAb was stable when exposed to low pH
      but lost binding capacity with KSCN. In all cases, the equilibrium constant was
      unchanged. The loss of capacity was also shown to be a strong function of
      antibody loading: at 14.5 mg/mL, 98% of the initial binding capacity of one MAb
      was lost within 40 cycles, versus 75% loss at 1 mg/mL. Antibody leakage and
      nonspecific adsorption of contaminants were not responsible for significant loss
      of antibody activity over time.

PMID- 1367172
TI  - Theoretical analysis of the effect of cell recycling on recombinant cell
      fermentation processes.
AB  - A cell recycle system is studied for two-stage continuous fermentation. Cell
      recycle around the second stage provides higher cell concentrations than
      processes without recycle and a longer residence time of the cell, which is
      necessary for inducible products, especially in recombinant cell fermentation.
      Residence time distribution of the cell in the fermentor is important for the
      optimization of inducible products. The residence time distributions are studied
      for the cases with and without significant cell growth in the second stage. With
      cell growth in the second stage, three cases are considered. These are the cases
      of (1) zero residence time for two daughter cells after the cell division, (2)
      zero residence time of one daughter cell after the cell division and inherited
      residence time for the other daughter cell from the mother cell after the cell
      division, and (3) two daughter cells having the residence time of the mother cell
      after the cell division.

PMID- 1367174
TI  - Activities of Candida rugosa lipase and other esterolytic enzymes coated on glass
      beads and suspended in substrate and water vapor: enzymes in thin liquid films.
AB  - Candida rugosa lipase was enzymatically active when coated on glass beads and
      exposed to mixtures of substrate and water vapor over a range of relative
      humidities up to 100%. Evidence was obtained for operation of the enzyme in a
      thin liquid film of concentrated buffer on the surface of the glass beads.
      Formation of the thin film was associated with hygroscopicity of the buffer used
      to suspend the enzyme in preparation of the enzyme-coated beads. At some buffer
      concentrations estimated to be on the bead surface, the enzyme was partially
      soluble and both soluble and insoluble forms were enzymatically active. The vapor
      mode of operation over a range of relative humidities had comparatively small
      effects on kinetic constants for hydrolysis of ethyl acetate, which were also
      similar to those in phosphate buffer. The extent of reaction occurred in the
      order hydrolysis greater than alcoholysis greater than ester interchange greater
      than esterification. Reaction preference between alcoholysis and hydrolysis
      changed as acyl chain length of substrate increased with C. rugosa lipase, as
      well as with Rhizopus arrhizus lipase and porcine liver esterase, with details
      depending on the enzyme. The vapor mode approach has the potential of being used
      with a wide variety of substrates, as shown by the ability to obtain hydrolysis
      at 30 degrees C with substrate vapor pressures as low as 0.08 mm Hg and with
      substrates with boiling points as high as 206 degrees C.

PMID- 1367175
TI  - Stabilization of enzymes by their specific antibodies.
AB  - In nature, increased stability of enzymes has often been found to be associated
      with noncovalent protein-protein interactions. Specific antibodies should be
      suitable for this purpose. To test this hypothesis, we used a number of model
      enzymes, complexed them with their specific antibodies, and exposed them and the
      free enzymes to low and high temperature, lyophilization, oxidation, and alcohol.
      The retained activity of the antibody-complexed enzymes was substantially, and in
      some cases dramatically, higher. In general mechanistic terms, stabilization may
      have been accomplished either by noncovalent antibody crosslinking of
      discontinuous oligopeptide chains on the surface of the enzyme, thereby
      increasing resistance to unfolding of the enzyme, or by physical shielding by the
      antibodies of vulnerable sites on the surface of the enzyme.

PMID- 1367173
TI  - Propagation of recombinant vaccinia virus in HeLa cells: adsorption kinetics and
      replication in batch cultures.
AB  - The influence of various culture parameters on infection and replication of
      recombinant vaccinia virus in HeLa cells was examined during various phases of
      viral replication. A modified form of the model of Valentine and Allison
      (Biochim. Biophys. Acta 1960, 40, 393-399) model was used to predict successfully
      the viral adsorption rates in cell suspensions. An experimentally determined
      aggregation factor, epsilon, was included in the model to account for deviations
      of the observed adsorption rates from those predicted by the earlier model. It
      was also shown that the ionic strength, ionic species, and serum proteins present
      in the medium significantly altered the adsorption kinetics of the virus. The
      lysosomotropic base chloroquine was found to enhance viral infection more than 2
      fold during the penetration step of viral infection. It was also demonstrated
      that cells infected during the exponential growth phase gave higher viral yields
      than those infected during the lag or stationary growth phases and the initial
      viral MOI did not significantly alter viral yields. Finally, it was demonstrated
      that viral infection of HeLa cells grown in 4-L bioreactor batch cultures
      resulted in increased death and glucose uptake rates and significantly lower
      growth rates.

PMID- 1367176
TI  - Automatic bioprocess control. 1. A general concept.
AB  - Automation of bioprocesses is presented and discussed. A general concept is
      applied to laboratory scale reactors as well as to large scale production
      facilities consisting of many unit operations with a hierarchical and highly
      modular structure. The implementation of non-dedicated and intelligent analytical
      subsystems is foreseen. Hard- and software requirements are discussed in view of
      the functional requirements of both scientific research and production
      engineering. Some practical experience is reported using several different
      components in parallel installations.

PMID- 1367177
TI  - A new method for estimating population doubling time of vertebrate cells.
AB  - Based upon the fact that the amount of DNA doubles after each cycle, a technique
      was developed in which the population doubling time for cell cultures was
      determined from the ratio of its DNA content to [3H]thymidine incorporation under
      conditions in which cell numbers cannot be readily determined. This technique may
      be useful in determining what proportion the sample is of the total cell
      population.

PMID- 1367178
TI  - Stability of mutant type II dihydrofolate reductase proteins in suppressor
      strains.
AB  - In the course of study of a (Glu-58 to Gln-58) mutant type II dihydrofolate
      reductase (DHFR), it was found that the altered DHFR was poorly produced in vivo.
      Investigations with several common laboratory Escherichia coli strains including
      htpR and lon strains bearing plasmids expressing the Gln-58 DHFR indicated a
      correlation of rapid degradation with the presence of a sup+ phenotype. The supo
      strain MC1061(p3) was transformed with a series of plasmids containing the Gln-58
      DHFR gene with and without an additional supF gene, and expression levels were
      compared. The supF+ constructs exhibited little accumulation of the Gln-58 DHFR,
      while reasonable levels were found in the supo cases. Experiments with extracts
      of plasmid-free sup+ and supo strains showed rapid degradation by certain strains
      compared to MC1061(p3) and this degradation was not dependent upon ATP. In
      another route to increasing the stability of labile DHFR derivatives, mutagenesis
      of a strain bearing a N-terminally shortened Gln-58 DHFR was performed. Selection
      and analysis of a trimethoprim-resistant stable mutant showed that this DHFR gene
      contained a triple repeat of leu-pro-ser in the enzymatically non-essential N
      terminal portion of the protein.

PMID- 1367179
TI  - Bioseparation using affinity techniques.
AB  - Bioseparation of proteins from dilute solutions using different novel affinity
      procedures is reviewed. Emphasis is also placed on the quality of the product
      separated. Whenever possible, physical insights into the separation procedure are
      provided, besides indicating suitable directions where appropriate further
      research may be carried out. The procedures analyzed are different affinity
      chromatographic techniques, affinity separation using liquid perfluorocarbon
      supports, water soluble nonionic surfactants for affinity bioseparations,
      affinity cross-flow filtration, bioaffinity separation using reversed micelles,
      affinity precipitation and dual-functional affinity protein purification.

PMID- 1367180
TI  - Solasodine production from self-immobilised Solanum aviculare cells.
AB  - Procedures were developed for 'self-immobilisation' of Solanum aviculare cells to
      eliminate the need for artificial immobilisation supports. Depending on the
      cytokinin used in liquid medium, compact aggregates 0.4-2.0 cm in diameter were
      formed without dispersed cells also being present. Histochemical analysis showed
      that the aggregates were structurally organised to facilitate nutrient transport.
      Growth, sugar uptake and solasodine production were measured in shake-flask
      cultures. Most of the product was stored in the aggregates to reach a maximum
      concentration of 0.3% dry weight; this is between 1.5 and 10 times the levels
      reported for suspended cells under similar conditions. A substantial amount of
      solasodine was produced after growth ceased. The maximum rate of solasodine
      production was about 0.22 mg g-1 d-1. A simple air-driven bioreactor was tested
      for culture of the aggregates; solasodine yields were comparable to those
      measured in shake flasks.

PMID- 1367181
TI  - Biotinylated probes to detect Leptospira interrogans on dot blot hybridization or
      by in situ hybridization.
AB  - Total genomic biotinylated probes which can identify leptospires by hybridization
      on filters or by in situ hybridization are described in this study. According to
      the weak G + C content of the strains studied (35-39%) and owing to the
      decreasing melting temperature (Tm) due to overbiotinylation, hybridization and
      wash temperatures were optimized at 33 degrees C and at 42 degrees C
      respectively. Fourteen serovars of Leptospira interrogans belonging to 11
      different serogroups and three serovars of Leptospira biflexa were used in this
      study. Cross-hybridization results show that it is possible, by means of such
      probes, specifically to recognize pathogenic strains. These probes did not
      hybridize with the three saprophytic strains: L. buenos-aires, L. patoc and L.
      andamana. We also ran a total genomic probe, specific to the serovar buenos-aires
      which hybridizes only with homologous DNA.

PMID- 1367182
TI  - Artificial organs from culture.

PMID- 1367183
TI  - Location and design: two sides of a coin.

PMID- 1367184
TI  - Transferring in vitro technology to the field.

PMID- 1367185
TI  - Chromatography of complex carbohydrates.

PMID- 1367186
TI  - Single chain antibody (SCA) encoding genes: one-step construction and expression
      in eukaryotic cells.
AB  - We report the expression, in eukaryotic cells, of a gene encoding a single chain
      antibody (SCA) and a rapid method for the construction of such genes. A SCA
      directed against the aromatic dye fluorescein was synthesized from a gene
      constructed by means of the simultaneous use of four PCR primers and templates of
      both light and heavy chain immunoglobulin cDNAs in the form of either plasmid
      clones or reverse transcribed hybridoma RNA. Two of the primers were partially
      complementary to one another and encoded the polypeptide linker which joins the
      immunoglobulin light and heavy chain variable domains of the SCA polypeptide. A
      functional, hapten-binding product was synthesized from the gene thus constructed
      in both E. coli and the fission yeast, Schizosaccharomyces pombe. Our results
      demonstrate that gene constructs encoding single chain antigen binding proteins
      can be synthesized very rapidly with only limited sequence information about the
      pertinent light and heavy chain immunoglobulin genes, and, that neither murine
      codon usage bias, Thermus aquaticus DNA polymerase infidelity, nor the eukaryotic
      cellular environment preclude the synthesis of functional single chain antigen
      binding proteins in non-lymphatic, non-murine eukaryotic cells.

PMID- 1367187
TI  - Heritable damage to yeast caused by transformation.
AB  - The introduction of plasmid DNA into yeast by transformation or electroporation,
      but not by cytoduction, results in the induction of a slow growth phenotype. This
      phenotype is inherited as a dominant Mendelian trait, which is only exhibited in
      the absence of the native 2 mu nuclear DNA plasmid of yeast. The use of
      recombinant DNA technology in yeast, therefore, does not necessarily manipulate
      the genome in a precise and completely defined way.

PMID- 1367188
TI  - Non-animal alternative toxicity tests for detergents: genuine replacements or
      mere prescreens?
AB  - Non-animal toxicity tests and testing strategies for use in identifying the
      potential toxic hazard of chemicals and products, and in providing information
      for use in risk and safety assessment, are in the course of development,
      validation and evaluation. Possible replacement alternatives to the rabbit Draize
      eye irritancy test are discussed, and results obtained for two in-vitro tests
      developed by FRAME (the kenacid blue test and the neutral red release test),
      applied to 19 surfactants and 32 formulations, are discussed. It is concluded
      that there are now legal and moral requirements that relevant and reliable non
      animal tests should be developed and accepted for use whenever possible.

PMID- 1367189
TI  - Analytical methods in biotechnology: introduction.

PMID- 1367190
TI  - Therapeutic peptides and proteins--challenges for the regulatory authorities.

PMID- 1367191
TI  - Electrophoretic techniques for protein analysis.

PMID- 1367192
TI  - Primary structure analysis of polypeptides.
AB  - Primary structure determination together with other techniques such as amino acid
      analysis, peptide mapping, and polyacrylamide gel electrophoresis provide a
      physical characterisation of a polypeptide. This has been valuable in the
      research field for some time, but is now being applied to problems which arise in
      the areas of process development, formulation and QA of protein products.
      Probably the most significant contribution is elucidation of processing events,
      since this may go undetected by other techniques. Thus, with the emergence of
      various protein products from biotechnology, a technique which has been of great
      value in research activities for many years is finding its place in the range of
      techniques used for process development, formulation and QA.

PMID- 1367193
TI  - Sequence analysis of N-linked oligosaccharides derived from glycoproteins and
      glycopeptides.

PMID- 1367194
TI  - Immunoassays for protein contaminants.

PMID- 1367195
TI  - Efficient production of human alpha-amylase by a Bacillus brevis mutant.
AB  - A cDNA for mature human salivary alpha-amylase was directly joined to a sequence
      encoding the signal peptide of the middle wall protein (MWP) gene of Bacillus
      brevis 47. This hybrid gene was placed downstream from the multiple promoter
      region of the MWP gene on a low copy-number plasmid vector, pHW1. B. brevis 47
      carrying the plasmid produced 0.9 mg/l of active human alpha-amylase in the
      medium. A B. brevis 47 mutant obtained on mutagenesis with N-methyl-N'-nitro-N
      nitrosoguanidine produced an increased amount of the alpha-amylase (6 mg/l). When
      the fused gene was inserted into a high copy-number expression vector, pNU200,
      and then introduced into the mutant, a large amount (60 mg/l) of the alpha
      amylase was produced in the medium. The alpha-amylase showed approximately the
      same specific activity and molecular weight as those of the natural enzyme. The
      mutant showed higher sensitivity to various antibiotics than the original strain,
      and altered cell wall and cytoplasmic membrane protein compositions. The results
      of reversion analysis suggested that a single mutation is responsible for the
      above phenotypes and hyper-productivity of human alpha-amylase.

PMID- 1367196
TI  - Effect of soil/contaminant interactions on the biodegradation of naphthalene in
      flooded soil under denitrifying conditions.
AB  - The mineralization of 14C-labelled naphthalene was studied in pristine and oil
      contaminated soil slurry (30% solids) under denitrifying conditions using a range
      of concentrations from below to above the aqueous phase saturation level. Results
      from sorption-desorption experiments indicated that naphthalene desorption was
      highly irreversible and decreased with an increase in the soil organic content,
      thus influencing the availability for microbial consumption. Under denitrifying
      conditions, the mineralization of naphthalene to CO2 occurred in parallel with
      the consumption of nitrate and an increase in pH from 7.0 to 8.6. When the
      initial substrate concentration was 50 ppm (i.e. close to the aqueous phase
      saturation level), about 90% of the total naphthalene was mineralized within 50
      days, and a maximum mineralization rate of 1.3 ppm day-1 was achieved after a lag
      period of approx. 18 days. When added at concentrations higher than the aqueous
      phase saturation level (200 and 500 ppm), similar mineralization rates (1.8 ppm
      day-1) occurred until about 50 ppm of the naphthalene was mineralized. After that
      the mineralization rates decreased logarithmically to a minimum of 0.24 ppm day-1
      for the rest of the 160 days of the experiments. For both of these higher
      concentrations, the reaction kinetics were independent of the concentration,
      indicating that desorption of the substrate governs the mineralization rate.
      Other results indicated that pre-exposure of soil to oil contamination did not
      improve the degradation rates nor reduce the lag periods. This study clearly
      shows the potential of denitrifying conditions for the biodegradation of low
      molecular weight PAHs.

PMID- 1367197
TI  - A hybrid bioreactor for high density cultivation of plant cell suspensions.
AB  - A hybrid bioreactor was developed for the production of secondary metabolites
      from high density cultivation of plant cell suspensions. Some of the advantages
      of both air-lift and cell-lift by agitation were combined. The addition of a
      decanting column also made it possible to run a perfusion system for high density
      culture or to run a two-stage culture efficiently. Cell growth and the production
      of berberine from Thalictrum rugosum in the hybrid bioreactor are reported in
      this paper. A cell density up to 31 g/l was obtained by perfusion without any
      problems in mixing or loss of cell viability and the specific berberine
      productivity was comparable to that in shake flasks. The maximum berberine
      concentration was 88 mg/l at 3 weeks of operation and declined thereafter.

PMID- 1367198
TI  - Long-term cultivation of anchorage-independent animal cells immobilized within
      reticulated biomass support particles in a circulating bed fermentor.
AB  - Long-term cultivation of anchorage-independent animal cells immobilized within
      porous biomass support particles (BSPs) using a gas-stirred circulating bed
      fermentor (CBF) was investigated. Inoculation of mouse myeloma MPC-11 (ATCC CCL
      167) cells into reticulated polyvinyl formal resin BSPs (3 x 3 x 3 mm; mean pore
      diameter, 60 microns; porosity, 0.88) and the repeated batch culture of
      inoculated cells were performed under gentle circulation of BSPs, induced by
      sparging air from the base of the fermentor. The glucose uptake rate of cells
      decreased in the initial period just after the start of circulation, since a
      relatively large number of cells leaked from the BSPs. After that period, the
      uptake rate gradually increased and the leakage of cells diminished. In the
      meantime, when inoculated cells were incubated statically by introducing air into
      days before circulating the BSPs, glucose consumption became very rapid and cell
      density in the BSPs reached at least 10(7) cells/cm3 BSP. Thus, a long-term
      cultivation without significant leakage of cells and with high cell density in
      BSPs was successfully achieved in the CBF-BSP system.

PMID- 1367199
TI  - Cultivation of anchorage-dependent animal cells in microsphere-induced aggregate
      culture.
AB  - Diethylaminoethyl-derivatized dextran microspheres were used to cultivate Chinese
      hamster ovary, 293, Vero and swine testicular cells. Cells became attached to the
      microspheres but did not spread out. Instead, they grew in a more spherical shape
      and eventually formed multiple-cell-layer aggregates. Viability in these
      aggregates remained high after the cultures reached high cell concentrations.
      This cultivation method allows a high cell density to be achieved with a low
      microsphere concentration.

PMID- 1367200
TI  - Genetic analysis of the phosphinothricin-tripeptide biosynthetic pathway of
      Streptomyces viridochromogenes Tu494.
AB  - Streptomyces viridochromogenes Tu494 produces the antibiotic phosphinothricyl
      alanyl-alanine (Ptt). Ptt-non-producing mutants were isolated following N-methyl
      N'-nitro-N-nitrosoguanidine (NTG) or UV light treatment of spore suspensions. In
      co-synthesis and bioconversion experiments the mutational blocks in the
      biosynthetic pathway were localized. The mutant NTG1 was analysed in detail. This
      mutant acts as a secretor for all other mutants. From bioconversion experiments
      with presumptive precursors circumstantial evidence was obtained that NTG1 is
      mutated in a gene involved in the alanylation of N-acetyl-demethyl
      phosphinothricin. Using a cosmid gene library the DNA region complementing the
      defective gene of mutant NTG1 was isolated on a 4-kb BamHI fragment. Subcloning
      experiments showed that a 3-kb BglII/BamHI fragment is sufficient for
      complementation of mutant NTG1.

PMID- 1367202
TI  - Denaturing capillary gel electrophoresis.

PMID- 1367201
TI  - Construction and physiological characterization of glyceraldehyde-3-phosphate
      dehydrogenase overproducing transformants of Aspergillus nidulans.
AB  - The construction and characterization of glyceraldehyde-3-phosphate-dehydrogenase
      (GPD) overproducing transformants of Aspergillus nidulans and their behaviour in
      acetate-limited continuous cultures and glucose-grown batch cultures are
      described. The A. nidulans acetamidase deletion strain MH1277 was transformed
      with the homologous gpdA gene on a vector with the homologous acetamidase-gene
      (amdS) as a selection marker. Transformant A1 contains about nine integrated
      copies of the gpdA gene, and shows a proportional gene-dosage GPD production of
      about 22% of the total soluble cell protein. Compared to the wild-type MH1277, A1
      has higher growth yields and reaches higher specific growth rates on both acetate
      and glucose, which could be due to the key position of GPD in glycolysis and
      gluconeogenesis.

PMID- 1367203
TI  - Simplified reading and storage of DNA sequence data.

PMID- 1367204
TI  - Biosensors. Surface plasmon resonance lights the way.

PMID- 1367205
TI  - Calcium inhibition of efrotomycin production by Nocardia lactamdurans.
AB  - Efrotomycin is a modified polyketide antibiotic of the elfamycin family that has
      use in the area of pig husbandry. Optimization of the fermentation medium for
      production of efrotomycin by Nocardia lactamdurans revealed that the fermentation
      is sensitive to hard water and certain lots of cottonseed flour used to prepare a
      complex fermentation medium. A limited metal ion analysis of the hard water
      indicated that calcium ions are present at concentrations found to be inhibitory
      by the addition of calcium chloride to medium prepared with distilled water.
      Similarly, a correlation between lots of cottonseed flour that poorly supported
      the fermentation and high calcium levels is presented. Further experimentation
      revealed that by altering the sterilization conditions of the cottonseed flour,
      the inhibitory effect of poor lots could be prevented.

PMID- 1367206
TI  - Structural analysis of Bacillus licheniformis 86 surfactant.
AB  - A tentative structure and composition of a surfactant, BL-86, produced by
      Bacillus licheniformis 86 is described. The surfactant is a mixture of
      lipopeptides with the major components ranging in size from 979 to 1091 Da and
      varying in increments of 14 Da. The variation in molecular weight represents
      changes in the number of methylene groups in the lipid and/or peptide portion of
      the surfactant. There are 7 amino acids per molecule. The peptide portion is
      composed of the following amino acids: glutamic acid or glutamine (glx), aspartic
      acid or asparagine (asx), valine, leucine, and isoleucine at a ratio of
      1.0:1.0:1.4:3.0:0.6, respectively. The leucine is present as both the D and L
      isomers at a ratio of about 2:1, respectively. Forty percent of the molecules
      contain L-valine instead of L-isoleucine. The glx and asx are present as a
      combination of L-glutamic acid and L-asparagine and/or L-glutamine and L-aspartic
      acid. The N-terminus of the peptide is blocked, most likely by a peptide bond to
      the lipid portion. An ester carbonyl structure is present, which could be a part
      of a lactone ring connecting the beta position of the lipid to one of the
      carbonyl groups in the peptide. The lipid portion is composed of, on average, 8-9
      methylene groups, and contains a mixture of linear and branched tails. Results of
      DCI-MS and FAB-MS analyses, as well as surface tension measurements, of purified
      BL-86 HPLC fractions support the proposed composition.

PMID- 1367207
TI  - Data-directed drug design.

PMID- 1367208
TI  - When microheterogeneity matters.

PMID- 1367209
TI  - Resource allocation to state agbiotech research: 1982-1988.

PMID- 1367210
TI  - Molecular biology of human muscle disease.
AB  - The molecular revolution that is transforming the entire biomedical field has had
      far-reaching impact in its application to inherited human muscle disease. The
      gene for Duchenne muscular dystrophy was one of the first cloned without
      knowledge of the defective protein product. This success was based upon the
      availability of key chromosomal aberrations that provided molecular landmarks for
      the disease locus. Subsequent discoveries regarding the mode of expression for
      this gene, the structure and localization of its protein product dystrophin, and
      molecular diagnosis of affected and carrier individuals constitute a paradigm for
      investigation of human genetics. Finding the gene for myotonic muscular dystrophy
      is requiring the brute force approach of cloning several million bases of DNA,
      identifying expressed sequences, and characterizing candidate genes. The gene
      that causes hypertrophic cardiomyopathy has been found serendipitously to be one
      of the genetic markers on chromosome 14, the beta myosin heavy chain.

PMID- 1367211
TI  - Production of human interleukin-3 using industrial microorganisms.
AB  - We expressed a cDNA encoding the multicolony stimulating factor interleukin-3 in
      a variety of cell types, including bacteria, yeast and mammalian cells. After
      evaluation of the advantages and disadvantages of each potential system, we
      designed a production and purification scheme using Bacillus licheniformis. The
      purification consists of hydrophobic interaction chromatography, two steps of ion
      exchange chromatography and gel filtration. The purified and formulated product
      entered clinical trials in November 1989.

PMID- 1367212
TI  - The case of the case study.

PMID- 1367213
TI  - Synthesis of wild type and mutant human hemoglobins in Saccharomyces cerevisiae.
AB  - We have expressed human alpha and beta-globin cDNA clones from separate,
      synthetic galactose-regulated hybrid promoters contained on a single plasmid in
      Saccharomyces cerevisiae. Co-expression of the alpha and beta-globin chains in S.
      cerevisiae results in the assembly of these proteins into soluble tetrameric
      hemoglobin that accumulates to 3-5 percent of the total cell protein.
      Endogenously produced heme is incorporated into the tetramer and the protein
      produced is functionally and structurally indistinguishable from human Ao
      hemoglobin. This expression system has been used to produce both wild type
      hemoglobin and a low O2-affinity hemoglobin mutant that has oxygen binding and
      dissociation characteristics similar to human whole blood. The yeast expression
      system we describe may be suitable for the production of a recombinant hemoglobin
      based blood substitute as well as for detailed structure-activity studies of
      human hemoglobin.

PMID- 1367214
TI  - High level expression of the humanized monoclonal antibody Campath-1H in Chinese
      hamster ovary cells.
AB  - We have cloned the light and heavy chain cDNAs for the humanized monoclonal
      antibody Campath-1H and expressed them in Chinese hamster ovary (CHO) cells using
      a dihydrofolate reductase (dhfr) amplification procedure. Each cDNA was
      positioned under control of the strong human beta-actin promoter/polyadenylation
      signals and used to evaluate alternative vector design and amplification
      procedures. By employing a dual selection co-transfection strategy, initial
      transformants accumulated antibody levels of 0.5 micrograms/ml after 4 days
      continuous culture. When subjected to successive rounds of selection in medium
      containing stepwise increments in methotrexate (MTX), stable cell lines were
      obtained that secreted up to 200 micrograms/ml of Campath-1H during the same
      period. This reflects a productivity of 100 micrograms/10(6) cells/day and
      demonstrates the potential of engineering CHO cells for the production of
      recombinant antibodies.

PMID- 1367215
TI  - Isolation and characterization of carotenoid hyperproducing mutants of yeast by
      flow cytometry and cell sorting.
AB  - The carotenoid pigment astaxanthin (3,3'-dihydroxy-beta,beta-carotene-4,4'-dione)
      is an important component in feeds of aquacultural animals. It is produced as a
      secondary metabolite by the yeast Phaffia rhodozyma, and the isolation of rare
      mutants that produce increased quantities is limited by the lack of genetic
      selections. As a model system for enriching mutants increased in production of
      secondary metabolites, we have used quantitative flow cytometry/cell sorting
      (FCCS) to isolate astaxanthin hyperproducing mutants of the yeast. Experimental
      conditions were developed that gave a quantitative correlation of fluorescence
      and carotenoid content. In mutated populations, a 10,000-fold enrichment of
      carotenoid-overproducing yeasts was obtained. Distinctive differences were
      detected by FCCS in fluorescence and forward scatter values of mutant and wild
      type populations of yeasts. Comparison of wild-type and mutant clones by
      fluorescence confocal laser microscopy showed that the mutants had more intense
      fluorescence throughout the cell than the wild-type. Quantitative FCCS is a
      sensitive method to isolate and characterize carotenoid overproducing mutants and
      should be useful as a general method for the isolation of mutants increased in
      other fluorescent metabolites.

PMID- 1367216
TI  - Unknown sequence amplification: application to in vitro genome walking in
      Chlamydia trachomatis L2.
AB  - A recently described technique, 'Chemical Genetics' unknown sequence
      amplification method, which requires only one specific oligonucleotide, has
      broadened the applicability of the polymerase chain reaction to DNA of unknown
      sequence. We have adapted this technique to the study of the genome of Chlamydia
      trachomatis, an obligate intracellular bacterium, and describe modifications that
      significantly improve the utility of this approach. These techniques allow for
      rapid genomic analysis entirely in vitro, using DNA of limited quantity or
      purity.

PMID- 1367217
TI  - Manipulation of Corynebacterium glutamicum by gene disruption and replacement.
AB  - We have developed a system for the genetic manipulation of the amino acid
      producing Corynebacterium glutamicum. Gene disruption and replacement were
      achieved by introducing, via conjugation, Escherichia coli vector plasmids
      carrying manipulated C. glutamicum DNA fragments. We obtained stable mutants in
      which the chromosomal lysA gene, encoding meso-diaminopimelate decarboxylase, was
      interrupted by a chloramphenicol resistance cartridge, or in which an essential
      internal part of the lysA gene was deleted. The deletion mutants retain neither
      antibiotic resistance markers nor vector sequences. This strategy is generally
      applicable to the construction of industrial strains to be used in fermentation
      processes.

PMID- 1367218
TI  - Rapid PCR-cloning of full-length mouse immunoglobulin variable regions.

PMID- 1367219
TI  - Thrombolytics and anti-coagulants from leeches.

PMID- 1367220
TI  - Research roundtable on inflammation.

PMID- 1367221
TI  - Prep-phoresis: a wealth of novel possibilities.

PMID- 1367222
TI  - A role for biotech in producing chemicals?

PMID- 1367223
TI  - Edwards Commission: weak Rx for ailing U.S. FDA.

PMID- 1367224
TI  - Antibody engineering: advances from the use of Escherichia coli expression
      systems.
AB  - Synthesis in Escherichia coli of correctly folded antibody fragments that bind
      antigen with the same affinity as the whole antibody is now possible. Here I
      review the techniques for achieving this and the physical properties of the
      various fragments produced. This technology not only facilitates antibody
      engineering but is also the basis of screening libraries for binding activity.
      Although the immunization of animals has not been made unnecessary in the
      production of monoclonal antibodies, steps toward this goal are now feasible.

PMID- 1367225
TI  - DNA amplification fingerprinting using very short arbitrary oligonucleotide
      primers.
AB  - The surprising finding that amplification of genomic DNA can be directed by only
      one oligonucleotide primer of arbitrary sequence to produce a characteristic
      spectrum of short DNA products of varying complexity, was applied as a strategy
      to detect genetic differences between organisms. This approach, DNA amplification
      fingerprinting (DAF), does not depend on cloning or DNA sequence information and
      can generate fingerprints from DNA of viral, bacterial, fungal, plant and animal
      origins. Primers as short as 5 nucleotides in length can produce complex banding
      patterns that are resolved by polyacrylamide gel electrophoresis and silver
      staining. Amplification fragment length polymorphisms (AFLPs) were detected
      between different human individuals as well as between soybean cultivars. It is
      anticipated that DAF will have wide application for DNA analysis.

PMID- 1367226
TI  - Fermentation of a yeast producing A. niger glucose oxidase: scale-up,
      purification and characterization of the recombinant enzyme.
AB  - We have developed a fermentation process to produce up to 3 grams per liter of
      active, secreted glucose oxidase from a recombinant Saccharomyces cerevisiae.
      Real-time size-exclusion HPLC analysis is used to monitor enzyme production
      during fermentation, and purification to more than 95 percent is obtained using
      only filtration methods. The recombinant enzyme is stable to higher temperatures
      and a wider pH range than the native Aspergillus niger enzyme, and is free of
      contaminating amylase, cellulase and catalase.

PMID- 1367227
TI  - A high containment polymodal pilot-plant fermenter--design concepts.
AB  - A 225 dm3 pilot-plant bioreactor system has been designed and constructed that is
      suitable for biohazardous fermentations. The design enables operation at
      containment levels above the requirements of good industrial large-scale practice
      (GILSP) without secondary containment of the whole plant. The main biosafety
      features of the systems include the use of steam barriers on O-ring seals, supply
      lines and stirrer seals, multiple O-ring seals, piping of condensate lines and
      pressure relief systems to a 'kill tank', double filtration of inlet and off
      gases and a mobile isolation unit that allows localised containment of sample
      valve and probe entry ports. The fermenter can, with minor modifications, be
      operated as a bottom-or top-stirred reactor for the culture of microbial or
      animal cells, or as an airlift reactor. The design offers considerable
      flexibility that could prove cost-effective for process development and
      production. The relevance of the various design features to enable bioreactor
      operations at pilot-plant scale to be carried out in compliance with current
      guidelines for large-scale culture of recombinant microorganisms and microbial
      pathogens is discussed.

PMID- 1367228
TI  - Inhibition of trypsin by t-butyloxycarbonyl-alpha-aza-(4-aminophenyl)alanine
      phenyl ester.
AB  - t-Butyloxycarbonyl-alpha-aza-(4-aminophenyl)alanine phenyl ester (III: R = NH2)
      has been synthesized. The rate of inhibition of trypsin (EC 3.4.21.4) by this
      compound (due to acylation followed by slower deacylation) shows a marked pH
      maximum at approximately 6. The shape of the pH-rate curve is discussed in terms
      of (i) the normal pH-activity curve of trypsin reacting with a charged substrate,
      i.e. the protonated form of the amino compound, (ii) the deprotonation of the 4
      amino group with pKa 4.3, and (iii) the lower rate of reaction of the enzyme with
      the uncharged, deprotonated form of the ester.

PMID- 1367229
TI  - A yeast biosensor for glucose determination.
AB  - A yeast potentiometric biosensor for glucose determination is described. After
      induction of glycolytic enzyme synthesis a cell suspension of the yeast Hansenula
      anomala is retained in calcium alginate gel on the surface of a glass electrode.
      This biosensor gives a Nernstian response in glucose concentration of 5 x 10(-4)
      5 x 10(-3) mol/l with a response time of 5 min and a life-time of at least 2
      months. Mannose and fructose are the only significantly interfering substances.
      The biosensor was used for measurement of glucose concentration in urine with
      results comparable to those obtained by a photometric enzymatic method.

PMID- 1367230
TI  - Increased yield of a lysozyme after self-cloning of the gene in Streptomyces
      coelicolor "Muller".
AB  - Streptomyces coelicolor "Muller" DSM3030 excretes a lysozyme comprising both beta
      1,4-N-acetyl- and beta-1,4-N,6-O-diacetyl muramidase activities. The lysozyme is
      named Cellosyl. Gene libraries have been established using genomic DNA from the
      wild-type strain, S. coelicolor DSM3030, and from an overproducing mutant, S.
      coelicolor HP1, which exhibits about a twofold increase in lysozyme production.
      The lysozyme-encoding genes (cel) from both strains were detected by
      oligodeoxynucleotide hybridization. The nucleotide sequence of the cel genes
      isolated from both strains was shown to be identical. The different levels of
      lysozyme production could not be correlated with any mutations at the cel gene
      locus. The cel gene isolated from the wild-type strain could not be expressed in
      some other species of Streptomyces. However, self-cloning of the cel gene into S.
      coelicolor DSM3030 and HP1 resulted in a 2.5-fold increase in lysozyme
      production.

PMID- 1367231
TI  - Dynamics of L-valine in relation to the production of cyclosporin A by
      Tolypocladium inflatum.
AB  - We report the kinetics of endogenous L-valine in the fungus Tolypocladium
      inflatum, in an effort to understand the enhancing effect of externally
      supplemented L-valine on the production of the immunosuppressant cyclosporin A
      (CyA) in chemically defined medium. In a batch laboratory stirred reactor
      cultivation, the concentration of intracellular L-valine increased by up to four
      times between the end of the exponential phase and the beginning of the
      stationary phase when the medium was supplemented externally with 4 g/l L-valine.
      The final CyA titre under these conditions was 710 mg/l compared to only 130 mg/l
      attained without L-valine supplementation. In contrast to substantial growth
      associated production of CyA in unsupplemented culture, the formation of the
      immunosuppressant was prolonged during the stationary phase in L-valine
      supplemented medium. As a result, the conversion yield of CyA on L-valine
      remained constant during the stationary phase at 0.27 g CyA/g L-valine.

PMID- 1367232
TI  - Degradation of isomeric monochlorobenzoates and 2,4-dichlorophenoxyacetic acid by
      a constructed Pseudomonas sp.
AB  - A 4-chlorobenzoate-degrading Pseudomonas sp. US1 was mated with a strain of
      Escherichia coli JMP 397 (harbouring the plasmid pJP4). An ex-conjugant
      designated Pseudomonas sp. US1 ex that could utilize all the isomeric
      monochlorobenzoates and 2,4-dichlorophenoxyacetate was obtained. The ex-conjugant
      released stoichiometric amounts of chloride when grown on these chloroaromatics
      as sole sources of carbon and energy.

PMID- 1367233
TI  - Fermentation and isolation of herbicolin A, a peptide antibiotic produced by
      Erwinia herbicola strain A 111.
AB  - Erwinia herbicola (Enterobacter agglomerans), belonging to the
      Enterobacteriaceae, produces the lipopeptide antibiotics herbicolin A and B,
      which are active against sterol-containing fungi. Fermentation of these
      antibiotics was performed in 20-l stirred glass fermentors in a batch process.
      Best yields of antibiotic production were found at low cultivation temperatures
      in a TRIS-buffered chemically defined medium. Under these conditions the amount
      of impurities aggravating the purification was minimized. Isolation was performed
      by adsorption, and gel and ion exchange chromatographic techniques. In a final
      purification step preparative high performance liquid chromatography (PHPLC)
      yielded pure herbicolin A.

PMID- 1367234
TI  - Response of mammalian cells to shear stress.
AB  - The influence of shear forces on adherent mammalian cells was investigated by
      means of a developed flow chamber. The viability of the cells decreased with
      increasing exposure level and duration. Additional, changes in the morphology of
      the cells due to the shear forces were observed.

PMID- 1367235
TI  - Automatic bioprocess control. 2. Implementations and practical experiences.
AB  - Our improved implementation for bioprocess control allows flexible responses to
      many process needs. It is based on computer equipment consisting of three
      hierarchically ordered levels. On the lowest level, a DDC slave computer handles
      setpoints and simple tasks generating the chemical and physical environment for
      the cells. It can be designed manually by the user or automatically by the
      supervisory computer on the second level. This provides for raw data
      organization, analysis and interpretation either to support personnel on line in
      decision making, to select predefined control strategies, or even to search for
      others. In the coordinating computer on the third level, common tasks of
      different supervisory computers (bioprocesses) are shared, saving money for the
      equipment. Tasks and concepts as well as experimental experiences are described
      to outline the capabilities of the configuration.

PMID- 1367236
TI  - Dielectric spectroscopy as a novel and convenient tool for the study of the shear
      sensitivity of plant cells in suspension culture.
AB  - Plant cell suspensions of different species and different age were subjected to
      hydrodynamic stress while following the decline in the volume fraction of intact
      cells by measuring the permittivity of the cell suspension at radio frequencies.
      Results were compared with the fresh weight, dry weight, packed cell volume and
      cell number of the suspensions. At first a rapid decline is seen as the most
      shear-sensitive cells are broken up, followed by a slower decline as less
      sensitive cells are broken up. The sensitivity of the cells to shear stress
      depended strongly on the cell line used but only slightly on their age, older
      cells being more sensitive. The dependence of the shear sensitivity on the cell
      line might be an effect of the species investigated, the culturing conditions of
      the cell line, or both. It was found that cells that grow in a finely dispersed
      suspension are much less prone to shear stress than is often assumed.

PMID- 1367237
TI  - Influence of low-temperature storage and glucose starvation on growth recovery in
      Escherichia coli relA and relA+ strains.
AB  - To study the influence of microgravity on bacterial growth behavior during a
      space mission, the special experimental conditions and the hardware environment
      necessitate storage of cells at low temperature, and permit a relatively short
      experimental period. Before this experimental period, cells have to recover their
      condition of steady-state growth, because it is only in this condition that the
      growth behavior of the flight and ground populations can be adequately compared.
      To meet these requirements and to obtain cells which recover rapidly their steady
      state growth, we analyzed the size and shape of Escherichia coli cells during
      storage at 4 degrees C, with and without previous glucose starvation of the
      cells. It appeared that cells stored at low temperature in the presence of
      glucose continued to increase in average mass and assumed ovoid shapes. In
      addition, upon restoration of maximal growth rate at 37 degrees C, they continued
      to increase in size and showed a transient overshoot of their final steady-state
      value, which was reached after about 5 h. Cells previously starved for glucose,
      however, maintained their average size and rod-shape during low-temperature
      storage. Recovery of the starved cells was most rapid in the relA+ strain which,
      contrary to the isogenic relA strain, showed no overshoot and reached its final
      steady-state size within 2 h.

PMID- 1367238
TI  - Genetic manipulation of Bacillus amyloliquefaciens.
AB  - Application of modern gene technology to strain improvement of the industrially
      important bacterium Bacillus amyloliquefaciens is reported. Several different
      plasmid constructions carrying the alpha-amylase gene (amyE) from B.
      amyloliquefaciens were amplified in this species either extrachromosomally or
      intrachromosomally. The amyE gene cloned on a pUB110-derived high copy plasmid
      pKTH10 directed the highest yields both in rich laboratory medium and in crude
      industrial medium. The alpha-amylase activity, when compared with the parental
      strain, was enhanced up to 20-fold in the pKTH 10 transformant. This strain
      showed decreased activities for other exoenzymes, such as proteases and beta
      glucanase suggesting common limiting resources in the processing of these
      enzymes. Deletions were made in vitro in genes encoding neutral (nprE), alkaline
      (aprE) protease and beta-glucanase (bglA). The engineered genes were cloned into
      the thermosensitive plasmid pE194, and the resulting plasmids were used to
      replace the corresponding wild type chromosomal genes in B. amyloliquefaciens by
      integration-excision at non-permissive temperature. The double mutant deficient
      in the major proteases (delta nprE delta aprE) showed about a 2-fold further
      enhancement in alpha-amylase production in the industrial medium compared with
      the relevant wild type background, [corrected] both when plasmid-free and when
      transformed with pKTH10; this strain also produced elevated levels of the
      chromosomally-encoded beta-glucanase; pKTH10 was stably maintained both in the
      wild type strain and in the delta nprE delta aprE mutant. We suggest that the
      higher yields in alpha-amylase and beta-glucanase in the delta nprE delta aprE
      strain are primarily due to improved access to limiting resources, and that
      decreased proteolytic degradation may have had a secondary role in retaining the
      high activity obtained.

PMID- 1367239
TI  - Polyvinyl alcohol and polyethylene glycol as protectants against fluid-mechanical
      injury of freely-suspended animal cells (CRL 8018).
AB  - Two identical bioreactors run in parallel were used to examine the
      phenomenological characteristics of two additives, polyethylene glycol (PEG) and
      polyvinyl alcohol (PVA), used as protectants against fluid-mechanical cell
      damage. Cell-protecting ability was evaluated by comparing apparent cell growth
      rates of freely suspended CRL-8018 hybridoma cells cultured in serum-free medium
      under surface aerated conditions whereby cell damage is due to bubble entrainment
      and breakup. PEG of various molecular weights was used to determine whether the
      size of the polymer has significant effects on PEG's cell-protecting
      capabilities. All the PEG's with molecular weights larger than 1400 showed
      similar protective effects. The effect of PEG concentration was then evaluated
      and results showed that concentrations greater than 0.05% w/v did not
      significantly improve the cell-protecting properties. Direct comparisons made
      between the PVA, PEG, and pluronic F68 as cell protectants showed that PEG
      protected cells better than F68 and that PVA provided even better protection than
      PEG. The mechanism of protection, fluid-mechanical or biological in nature, was
      examined by growing the cells in additive from the beginning of the experiment
      (long-term exposure), or adding the additive after the cells had been agitated at
      rates detrimental to the cells (short-term exposure). In agreement with results
      reported previously on PEG and F68, fast-acting protection was seen. This implies
      a fluid-mechanical rather than a biological protection mechanism. In an attempt
      to correlate interfacial properties of the resulting media with shear protection,
      interfacial tension and viscosity measurements of all the media were made. On the
      basis of these measurements, we find no definitive correlations for evaluating
      these additives' cell-protecting capabilities.

PMID- 1367240
TI  - Use of ars18 based vectors to increase protein production in Yarrowia lipolytica.
AB  - The isolation of ars sequence from the yeast Yarrowia lipolytica has recently
      been reported (Fournier et al., 1991). Vectors containing ars18 have been used to
      increase homologous and heterologous protein production. Examples presented are
      the Yarrowia lipolytica alkaline extracellular protease (AEP), the porcine alpha
      1-interferon and the bovine prochymosin. A 2- to 6-fold increase in the
      corresponding protein production was observed and in several cases it was
      established that it corresponded to the copy number of plasmid in the cell.

PMID- 1367241
TI  - The 1,4-beta-D-glucan cellobiohydrolases from Phanerochaete chrysosporium. I. A
      system of synergistically acting enzymes homologous to Trichoderma reesei.
AB  - A physico-chemical and structural characterization of three 1,4-beta-D-glucan
      cellobiohydrolases (EC. 3.2.1.91), isolated from a culture filtrate of the white
      rot fungus Phanerochaete chrysosporium, reveals that the cellulolytic enzyme
      secretion pattern and thus the general degradation strategy for P. chrysosporium
      is similar to that of Trichoderma reesei. Partial sequence data show that two of
      the isolated enzymes, i.e., CBHI, pI 3.82 and CBH62, pI 4.85, are homologous with
      CBHI and EGI from T. reesei; while, the third, i.e., CBH50, pI 4.87, is
      homologous to T. reesei CBHII. Limited proteolysis with papain cleaved each of
      the three enzymes into two domains: a core protein which retained full catalytic
      activity against low molecular weight substrates and a peptide fragment
      corresponding to the cellulose binding domain, in striking similarity to the
      structural organization of T. reesei. CBHI and CBH62 have their binding domain
      located at the C-terminus, whereas in CBH50 it is located at the N-terminus. It
      is evident that synergistically acting cellobiohydrolases is a general
      requirement for efficient hydrolysis of crystalline cellulose by cellulolytic
      fungi.

PMID- 1367242
TI  - Cloning and expression in Escherichia coli of mercuric ion resistance coding
      genes from Zymomonas mobilis.
AB  - From a genomic library of Zymomonas mobilis prepared in Escherichia coli, two
      clones (carrying pZH4 and pZH5) resistant to the mercuric ion were isolated. On
      partial restriction analysis these two clones appeared to have the same 2.9 kb
      insert. Mercuric reductase activity was assayed from the Escherichia coli clone
      carrying pZH5 and it was Hg(2+)-inducible, NADH dependent and also required 2
      mercaptoethanol for its activity. The plasmid pZH5 encoded three polypeptides,
      mercuric reductase (merA; 65 kDa), a transport protein (merT 18-17 kDa) and merC
      (15 kDa) as analysed by SDS-PAGE. Southern blot analysis showed the positive
      signal for the total DNA prepared from Hgr Z. mobilis but not with the Hgs strain
      which was cured for a plasmid (30 kb). These results were also confirmed by
      isolating this plasmid from Hgr Z. mobilis and transforming into E. coli.
      Moreover the plasmid pZH5 also hybridized with the mer probes derived from Tn21.

PMID- 1367243
TI  - Biotechnology in Japan--towards the year 2000 ... and beyond.

PMID- 1367244
TI  - Application of reversibly soluble polymers in bioprocessing.
AB  - Reversibly soluble polyelectrolytes, whose solubility in aqueous solutions is
      dependent on factors such as pH or ionic strength, may be used as supports for
      enzymes or affinity ligands. Their dual nature may be exploited to take advantage
      of the soluble form during, for example, enzymatic reactions, and the insoluble
      form during downstream processing operations for enzyme or product recovery.

PMID- 1367245
TI  - Protein adsorption to solid surfaces.
AB  - The phenomenon of protein adsorption to solid surfaces affects the performance of
      many materials and processes, in areas ranging from medicine to biochemical
      engineering. Controlling protein adsorption, from solutions of single proteins as
      well as from more complex mixtures, requires an understanding of the mechanism(s)
      by which it occurs. This, in turn, entails detailed characterization of both the
      protein and the solid surface and identification of those factors controlling the
      adsorption process.

PMID- 1367246
TI  - Conformational features of signal sequences and folding of secretory proteins in
      yeasts.
AB  - A yeast secretion system has been used extensively for the production of
      eukaryotic proteins that are expressed as non-native aggregates in E. coli.
      Secretory proteins translocate through the membrane using signal sequences, and
      fold in the cells (probably with the aid of several molecular chaperones). In
      combination with recent techniques of mutagenesis, this system has recently been
      implemented to study structure/function in signal sequences, and in vivo folding
      mechanisms of proteins. This review focuses on approaches to conformational
      features of signal sequences and folding of secretory proteins in yeasts.

PMID- 1367247
TI  - New approaches to the study of tumor drug resistance.
AB  - The development of tumor drug resistance is the major obstacle to successful
      systemic chemotherapy. Therefore, devising methods for reversing drug resistance
      is a high priority and could lead to significant improvements in cancer
      treatment. The mechanisms of tumor drug resistance are manifold and are not well
      understood. The phenomenon of multidrug resistance (MDR) represents the
      development of resistance to most drugs, regardless of their chemical structure.
      Several types of MDR are known, for example, the overexpression of a cell
      membrane glycoprotein (P-170), increased activity of glutathione S-transferase,
      elevated levels of glutathione (GSH), and alterations in topoisomerase action. A
      partial reversal of tumor drug resistance has been achieved by the use of
      competitive inhibitors for the function of glycoprotein P-170, or by the
      inhibition of GSH synthesis; however, this strategy has not been substantially
      successful for improving the response of human tumors to clinical therapy. We
      have recently used electroporation, in conjunction with the cytotoxic drug,
      cisplatin (cDDP), in an attempt to circumvent drug resistance in cDDP-resistant
      mouse tumor cells (RIF/Ptr1). Electroporation is the application of a high
      voltage electric shock which is known to create transient pores in plasma
      membranes of cultured cells. Electroporation plus cDDP treatment increased
      intracellular cDDP concentration and reversed cellular resistance to cDDP-induced
      cell killing.

PMID- 1367248
TI  - Eukaryotic gene regulation: simple vs complex models.
AB  - The current generally accepted model of eukaryotic gene regulation is essentially
      a simple one. Regulatory proteins containing separable DNA binding and
      transcriptional activation domains, bind to specific DNA sequences in promotors
      and interact directly or indirectly with the TATA Box binding factor to increase
      the rate of transcription initiation at selected promotors. Here we present
      observations suggesting that the process may be more complex.

PMID- 1367249
TI  - Targeting of gene expression to skeletal and cardiac muscle of trangenic animals.
AB  - The tissue restricted and developmental potentiation of transcription by chicken
      alpha-skeletal actin promoter regions fused to the reporter gene chloramphenicol
      acetyl transferase (CAT) were characterized in transgenic mice. Six of eight
      expressing transgenic mouse lines containing the chicken alpha-skeletal actin
      promoter fused to CAT resulted in preferential transgene transcription in
      skeletal muscle tissue, similar to the endogenous mouse alpha-skeletal actin
      gene. Two of the eight lines departed from the preferred pattern of skeletal
      muscle expression with primary expression of the transgene in the heart, a tissue
      containing primarily cardiac actin isoforms. Developmentally, a transition from
      embryonic heart to fetal and neonatal skeletal muscle expression was produced by
      the transgene promoter, a pattern of regulation similar to that of the endogenous
      alpha-skeletal actin gene. Instances of departure of transgene expression from
      the endogenous gene implied the existance of higher order muscle gene regulatory
      mechanisms.

PMID- 1367250
TI  - Mass culture of mammalian cells as a national project.

PMID- 1367251
TI  - Optimization of cell culture conditions for production of biologically active
      proteins.
AB  - We investigated the basic technology of cell culture conditions for production of
      useful substances such as cytokines, and related proteins produced by Namalwa
      cells. Namalwa cells (Klein, 1972), human B lymphoblastoid cells, were used for
      large scale production of alpha-interferon (Klein, 1979). Namalwa KJM-1, a
      subline of Namalwa cells, adapted to serum- and albumin-free medium, can grow at
      a high density above 1 x 10(7) cells/ml in suspension mode by the use of a
      perfusion culture system, Biofermenter, containing a cone-type cell-sedimentation
      column as cell separator (Sato, 1983). Several kinds of cytokine cDNA can be
      introduced and expressed in Namalwa KJM-1 cells (Miyaji, 1990a,b,c). Some of
      these were produced in large quantities by use of a gene amplification method
      with dhfr (Miyaji, 1990c), even though the Namalwa KJM-1 cells contained
      endogenous dhfr genes. For stable production of the target protein, Namalwa KJM-1
      cells are very useful host cells, because they have no effective endogenous
      protease activity in the conditioned medium. Using Biofermenter with micro
      silicone fibers and a dialysis system, the specific productivity of the target
      proteins was not depressed at a high cell density.

PMID- 1367252
TI  - Japanese animal cell biotechnology opens to the world.

PMID- 1367253
TI  - Development of a serum-free and heat-sterilizable medium and continuous high
      density cell culture.
AB  - We tried to establish a new serum-free and heat-sterilizable medium, based on our
      serum-free medium in which many lymphoblastoid cells and hybridoma could grow as
      well as in a conventional serum-containing medium. As is well-known, L-glutamine
      (L-Gln) is one of the most heat-labile but essential components for cell growth.
      As a substitute for L-Gln, dipeptide such as Gly-L-Gln or L-Ala-L-Gln, which was
      quite stable even after autoclaving, was found to be utilizable for mammalian
      cell growth. The L-Gln dipeptide-containing serum-free medium was quite stable in
      a solution even after storing at 37 degrees C for 4 months. In the serum-free
      medium containing L-Ala-L-Gln, mouse hybridola could grow and produce more
      antibody than in RPMI 1640 + 10% FBS. It has been proved that BSA and
      transferrin, which are also heat-labile but essential for the growth of various
      cell lines, can be substituted by heat-stable alpha-cyclodextrin and cholesterol,
      and Fe-gluconate, respectively. Insulin has also proved to be heat stable in a
      solution of Fe-gluconate. We thus established a new serum-free medium, all the
      components of which could be heat-sterilizable. Moreover, by adding EGF and BSA
      but without the adhesion factor included in FBS, the serum-free medium was found
      to support a long-term serial culture of a human diploid fibroblast. Finally,
      with this auotoclavable serum-free medium in a perfusion culture apparatus, we
      were able to continuously cultivate a human lymphoblastoid cell line. The
      production rate of IgM was found to be markedly increased by feeding the serum
      free medium enriched by glucose, bicarbonate, L-Cys, and approtinin. The cell
      density reached as high as 2 x 10(8)/ml in the serum-free medium. Although the
      working volume in the reactor was only 1 1, the rate of IgM production reached
      480 mg/day. The new heat-sterilizable serum-free medium has several advantages,
      because L-Gln peptide is a heat-stable and available precursor of L-Gln.

PMID- 1367254
TI  - Effective production of anti-tetanus toxoid and anti-HBsAg human monoclonal
      antibodies by serum-free culture of hybridomas.
AB  - Two hybridoma systems, mouse.human-human (m.h-h) heterohybridoma and human-human
      (h-h) hybridoma, have been established, and hybridomas secreting anti-tetanus
      toxoid and anti-HBsAg human monoclonal antibodies (MoAbs), both having a
      neutralizing activity have been obtained. Cell-line improvement was shown to be
      an efficient method for improving the productivity in a cell culture process. Two
      kinds of serum-free media, GFS (a serum substitute)-containing media and
      polyethylene glycol (PEG)-containing media, have been established to produce
      human MoAbs. m.h-h Heterohybridomas could be cultivated for a long period by
      perfusion culture in an agitation vessel, but h-h hybridomas could not. We found
      that h-h hybridomas show growth-associated antibody production kinetics and
      established two kinds of long-term cultivation systems: continuous perfusion
      culture and semi-continuous immobilized perfusion culture. We also scaled up
      batch culture and short-term perfusion culture to 200-L and 50-L fermentors,
      respectively. Processes for large-scale purification from the culture
      supernatants of both GFS- and PEG-containing serum-free media have also been
      developed.

PMID- 1367255
TI  - Establishment of vascular endothelial cell lines in a serum-free culture and the
      discovery of endothelin and a vasoactive intestinal contractor (VIC).
AB  - Immortal vascular endothelial cell lines were established and utilized for the
      production of an endothelium-derived contraction factor (EDCF) in a serum-free
      medium. After the discovery of Endothelin (21 amino acid peptide, ET) as an EDCF,
      a prepro ET cDNA isolated from human tissue was used to examine the expression of
      ET and its regulation in human endothelial cells. A gene family of ET was shown
      in mouse by using prepro ET cDNA as a probe. Thus, a novel peptide, Vasoactive
      Intestinal Contractor (VIC) homologous to ET was deduced from the sequence of one
      of these genes. VIC was confirmed to induce vasocontraction as well as intestinal
      contraction. Northern blot analysis indicated that this gene was expressed in the
      intestine but not in endothelial cells. A cloning and sequencing of prepro VIC
      cDNA from mouse intestine suggest that a VIC-like peptide, as well as VIC, are co
      synthesized by cleavage from prepro VIC with 160 amino acids.

PMID- 1367256
TI  - Serum-free cultivation of anchorage-dependent cells on microcarrier: effective
      production of human macrophage colony-stimulating factor.
AB  - For the purpose of establishing a large scale production process of biologically
      active substances by cultivation of anchorage-dependent mammalian cells, basic
      studies were carried out on the following items; establishment of a new cell line
      and derivation of high productivity; construction of optimal serum-free medium;
      optimization of cultivation method using microcarrier in serum-free medium; and
      establishment of purification process. The cell line, TRC-29SF, used in this
      study was newly established from human renal carcinoma with a function of
      producing macrophage colony-stimulating factor constitutively. Improvement of M
      CSF productivity upon TRC-29SF cell line was performed by M-CSF gene
      amplification with dhfr-MTX system and by truncation of membrane-binding amino
      acid sequence by recombinant DNA technique. Two kinds of serum-free media, IPEG
      85 and IREG-89, were formulated for the growth of TRC-29SF cell and its
      transformant, respectively. A new cell-adhesion method which permits homogeneous
      attachment to microcarrier in short term was developed by equalizing the
      sedimentation velocity between cells and microcarrier by addition of 7% Ficoll
      into the medium. High cell density perfusion culture of TRC-29SF cells was
      achieved by microcarrier method using IPEG-85 medium, and final cell density
      reached over 10(7) cells/ml. Based on the results obtained, long-term perfusion
      cultures were performed using Mn10-5 and Mn10-5/R600 cell lines, which were
      created by M-CSF gene transfection and amplification. We found that the
      productivity of M-CSF per cell began to decrease from the end of logarithmic
      growth phase. Long-term cultivation with high productivity was accomplished by
      perfusing medium containing 2 mM sodium butyrate. Purification process for M1-CSF
      from the culture supernatant of transformed cell line was also established.

PMID- 1367257
TI  - Influence of system and molecular parameters upon fractionation of intracellular
      proteins from Saccharomyces by aqueous two-phase partition.
AB  - The interaction of molecular characteristics of proteins with the physicochemical
      properties of PEG-phosphate aqueous two-phase systems has been studied. This has
      involved characterization of protein molecular weight, charge, and hydrophobicity
      and study of PEG molecular weight and concentration, phosphate concentration, and
      pH. System characterization has been conducted in the context of limited stage
      fractionation procedures for protein recovery from baker's yeast. Results are
      presented which show that the degree of purification achieved is dependent on
      macromolecular surface properties rather than system operating conditions. A
      simple conceptual model of partitioning in PEG-phosphate aqueous two-phase
      systems is presented which is applicable in the rational design of fractionation
      procedures and serves to limit the amount of empirical experimentation necessary
      for the establishment of practical operations.

PMID- 1367258
TI  - Immobilized enzyme system for determination of sialic acid in serum or urine.
AB  - An immobilized enzyme system has been developed and employed to determine the
      concentration of sialic acid (N-acetylneuraminic acid) in human serum and urine.
      Two enzyme pairs, neuramindiase-Neu-5-Ac lyase and pyruvate oxidase-peroxidase,
      have been respectively co-immobilized onto 1,12-aminododecane-agarose with
      glutaraldehyde. The relative specific activity of the co-immobilized
      neuraminidase and Neu-5-Ac lyase were 60% and 78%, and those of pyruvate oxidase
      and peroxidase were 50% and 95% of the corresponding soluble enzymes,
      respectively. The optimal reaction pH at 37 degrees C for each of the co
      immobilized enzymes was about one pH unit higher than that of the corresponding
      soluble enzyme. The optimal reaction temperature of each enzyme was increased as
      a result of immobilization. The thermal stability at 45 degrees C of the
      immobilized neuraminidase, Neu-5-Ac lyase, pyruvate oxidase, and peroxidase were
      increased 80-, 83-, 115-, and 147-fold, respectively. Km and Vm of each
      immobilized and co-immobilized enzyme have also been determined. The system
      provided a convenient and rapid method to determine the concentration of total
      sialic acid without pretreatment of the sample. The results correlated
      satisfactorily with those obtained by using a soluble enzyme system. The co
      immobilized enzymes were stable for at least 1 year of 500 tests when used
      repeatedly. The system is thus a reproducible and reliable novel assay method for
      sialic acid in the serum or urine sample.

PMID- 1367259
TI  - Isolation and thermal stability studies of two novel serine proteinases from the
      fungus Tritirachium album Limber.
AB  - A number of serine proteinases are secreted into the culture medium when
      Tritirachium album Limber is supplied with protein as the only nitrogen source.
      From this population of proteinases, we have isolated two novel proteolytic
      enzymes, designated as proteinase R and T. We have compared the thermal stability
      of these two proteinases with that of subtilisin BPN' and proteinase K. Both of
      these proteinases were thermally stable in the absence of detergents in buffers
      of low (4.0) and high (10.0) pH. The thermal stability of proteinase T was not
      affected by the presence of 1.0% SDS either at pH 8.0 or 10.0 in contrast to
      proteinase R which became heat labile. At low pH, the presence of SDS was
      detrimental to the stability of all the proteinases.

PMID- 1367260
TI  - Expression of active recombinant human alpha 1-antitrypsin in transgenic rabbits.
AB  - A DNA construct containing the human alpha 1-antitrypsin gene including 1.5 and 4
      kb of 5' and 3' flanking sequences, was microinjected into the pronucleus of
      rabbit embryos. The recombinant human protein was (a) expressed in the blood
      circulation of F0 and F1 transgenic rabbits at an average concentration of 1 mg
      ml-1, (b) shown to be fully active and (c) shown to be separable from its rabbit
      counterpart. Transgenic rabbits might represent a novel source of human proteins
      of therapeutic interest.

PMID- 1367261
TI  - Flavone glycosides from Asplenium normale.
AB  - Eight flavone glycosides were isolated from fronds of Asplenium normale, its two
      varieties, var. boreale and var. shimurae, and related species, A. oligophlebium.
      Six of the glycosides were identified: apigenin 7-O-dirhamnoside and 7-O
      glucosylrhamnoside, luteolin 7-O-dirhamnoside and 7-O-glucosylrhamnoside,
      genkwanin 4'-O-glucosylrhamnoside, and vicenin-2. The remaining two glycosides
      were tentatively characterized as genkwanin 4'-O-glycoside and 6,8-di-C
      glycosylluteolin. The four taxa analysed in this survey all had distinctive
      flavonoid profiles.

PMID- 1367262
TI  - Scammonins I and II, the resin glycosides of radix scammoniae from Convolvulus
      scammonia.
AB  - The ether-soluble resin glycoside ('jalapin') fraction obtained from scammony
      roots, on alkaline hydrolysis, gave a glycosidic acid, scammonic acid A, together
      with isobutyric, 2S-methylbutyric and tiglic acids. In addition, two kinds of
      resin glycosides, named scammonin I and II, were isolated and characterized,
      respectively, as (11S)-hydroxyhexadecanoic acid, 11-[( O-6-deoxy-4-O-(2(E)-methyl
      1-oxo-2- butenyl)-beta-D-glucopyranosyl-(1----4)-O-6-deoxy-2-O-(2-methyl-1-oxobut
      yl)- alpha-L-mannopyranosyl-(1----2)-O-beta-D-glucopyranosyl-(1----2)-6-deoxy 
      beta- D-glucopyranosyl]oxy)-, intramol. 1,3"'-ester and (11S)-hydroxyhexadecanoic
      acid, 11-[( O-beta-D-glucopyranosyl-(1----4)-O-6-deoxy-2-O-(2-methyl-1-oxobutyl)-
      alpha-L-mannopyranosyl-(1----2)-O-beta-D-glucopyranosyl-(1----2)-6-deoxy -beta-D 
      glucopyranosyl]oxy)-, intramol. 1,3"'-ester.

PMID- 1367263
TI  - Kaempferol glycosides from Hosta ventricosa.
AB  - Leaves of Hosta ventricosa yielded eight kaempferol glycosides, of which six: the
      3-(2G-glucosylrutinoside)-7-glucoside, 3-sophoroside-7-glucoside, 3-rutinoside-7
      glucoside, 3-(2G-glucosylrutinoside), 3-sophoroside, 3-rutinoside were fully
      characterized and two: the 3-xylosylrutinoside-7-glucoside and 3
      xylosylrutinoside were tentatively identified. Investigations included 1H-1H COSY
      and 1H-1H 2D J NMR analysis.

PMID- 1367264
TI  - Clematoside-S, a triterpenoid saponin from the roots of Clematis grata.
AB  - Clematoside-S, a new triterpenoid saponin from the roots of Clematis grata, has
      been identified by chemical and spectroscopic methods as hederagenin-3-O-beta-D
      ribopyranosyl (1----3)-alpha-L-rhamnopyranosyl(1----2)-alpha-L-arabinopyranoside
      .

PMID- 1367265
TI  - Two flavonol glycosides from Chenopodium quinoa.
AB  - Two new flavonol glycosides from the seeds of Chenopodium quinoa have been
      isolated. Their structures were established as kaempferol 3-apiofuranosyl(1"'---
      2")rhamnopyranosyl(1""----6")galactoside and kaempferol 3-apiofuranosyl(1"'---
      2")rhamnopyranosyl(1""----6")galactoside. The main flavonoid glycoside was
      kaempferol 3-(2,6-dirhamnopyranosyl)galactoside.

PMID- 1367266
TI  - A cardenolide tetraglycoside from Oxystelma esculentum.
AB  - A new cardenolide tetraglycoside, oxyline, was isolated from the dried roots of
      Oxystelma esculentum. On the basis of chemical and spectroscopic evidence the
      structure of oxyline was established as 3-epi-uzarigenin-3-O-beta-D
      cymaropyranosyl-(1----4)-O-beta- D-thevetopyranosyl-(1----4)-O-beta-D
      cymaropyranosyl- (1----4)-O-beta-D-digitoxopyranoside.

PMID- 1367267
TI  - The amino acid sequence of ferredoxin from Hordeum vulgare.
AB  - Ferredoxin from barley consists of a single polypeptide chain of 97 amino acids,
      four of which are cysteine. These residues, which bind the iron atoms of the
      active centre, are in identical positions to those of other ferredoxins. The
      primary structure shows considerable similarity with other plant ferredoxins.

PMID- 1367268
TI  - An anticoagulant fucoidan from the brown seaweed Ecklonia kurome.
AB  - The structure of a alpha-L-fucose-rich, sulphated polysaccharide (C-I) with a
      potent anticoagulant activity, which was isolated from the brown seaweed Ecklonia
      kurome, has been studied. Methylation analysis showed that C-I consisted mainly
      of 3-linked and 3,4-disubstituted fucopyranosyl residues in addition to non
      reducing terminal fucofuranosyl and fucopyranosyl residues, 2,3-di- and 2,3,4-tri
      substituted fucopyranosyl residues and galactopyranosyl residues with various
      glycosidic linkages. Methanolysis of C-I gave neutral di-, tri-, tetra- and
      highly polymerized-oligosaccharide fractions. GC-MS and methylation analysis
      indicated that di- and trisaccharide fractions consisted mainly of Fuc-(1----3)
      Fuc and Fuc-(1----3)-Fuc-(1----3)-Fuc, respectively, in addition to small amounts
      of Fuc-(1----4)-Fuc, Fuc-(1----4)-Gal and Fuc-(1----3)-[Fuc-(1----2)-]Fuc. When
      methylated C-I was subjected to methanolysis for desulphation followed by
      remethylation with deuterated methyl iodide, most of deuteriomethyl groups
      substituted to position 4 of 3-linked Fuc.

PMID- 1367269
TI  - 12-Keto steroidal glycosides from the caudex of Yucca gloriosa.
AB  - Eight new steroidal glycosides, tentatively named YS-VI, -VII, -VIII, -IX, -X, 
      XI, -XII and -XIII were isolated from the caudex of Yucca gloriosa along with P
      1, YG-2 and YG-3 previously obtained from flowers. The structures of five of
      these compounds were elucidated as mexogenin 3-O-beta-D-glucopyranosyl-(1----2)
      beta-D-galactopyranoside (YS-VI), gloriogenin 3-O-beta-D-glucopyranosyl-(1----2)
      [beta- D-glucopyranosyl-(1----3)]-beta-D-glucopyranoside (YS-VII) and 3-O-beta-D
      glucopyranosyl-(1----2)-[beta-D-glucopyranosyl)-(1----3)]- beta-D
      galactopyranoside (YS-VIII), manogenin 3-O-beta-lycotetraoside (YS-IX) and 3-O
      alpha-L-rhamnopyranosyl-beta-lycotetraoside (YS-X), respectively, on the basis of
      chemical and spectral evidence.

PMID- 1367270
TI  - Isolation of steroidal glycoalkaloids from Solanum incanum by two countercurrent
      chromatographic methods.
AB  - Using a bioassay for inhibition of plant growth and a combination of two
      countercurrent chromatographies: rotation locular countercurrent chromatography
      and droplet countercurrent chromatography, two biologically active glycosidal
      alkaloids, solasonine and solamargine were isolated from fresh ripe fruit of
      Solanum incanum. The combination of these chromatographic techniques has
      established an efficient isolation of polar phytochemicals of steroidal
      glycoalkaloids.

PMID- 1367271
TI  - Brandioside, a phenylpropanoid glycoside from Brandisia hancei.
AB  - A new phenylpropanoid glycoside, brandioside, was isolated from Brandisia hancei.
      Its structure, [beta-(3',4'-dihydroxylphenyl)-ethyl]-(2-O-acetyl)-(3,6-O-di-alpha
      -L-rhamnopyranosyl)-(4-O-caffeoyl)-beta-D-glucopyranoside, was established by
      chemical and spectroscopic methods.

PMID- 1367272
TI  - An anthraquinone and three naphthopyrone derivatives from Cassia pudibunda.
AB  - Chemical examination of the methanolic extract of the roots of Cassia pudibunda
      led to isolation of the new rubrofusarin-6-O-beta-D-glucopyranoside,
      quinquangulin-6-O-beta- D-apiofuranosyl-(1----6)-O-beta-D-glucopyranoside,
      quinquangulin-6-O-beta-D-glucopyranoside and chrysophanol dimethyl ether.
      Moreover the known chrysophanol, physcion, cis-3,3',5,5'-tetrahydroxy-4
      methoxystilbene, trans-3,3',5,5' -tetrahydroxy-4-methoxystilbene, and cassiaside
      B were identified. The antimicrobial activity of some of these compounds is also
      reported.

PMID- 1367273
TI  - Continuous aqueous phase extraction of proteins: automated on-line monitoring of
      fumarase activity and protein concentration.
AB  - Automated assay techniques are described for on-line measurements of fumarase
      activity and total protein concentration, including in-line sample dilution and
      sample multiplexing during continuous aqueous phase extraction. Fumarase was
      determined by following the conversion of L-malate to fumurate at a wavelength of
      250 nm, while the protein assay was based on the Biuret reaction. Actual assay
      times of 2 and 4 min were achieved for the fumarase and protein measurements,
      respectively, with an effective measurement cycle time of 2 min. Standard
      deviations of c. 3.2 and 2% of the measured values were calculated for the enzyme
      and protein values, respectively. The assay system was coupled to a computer to
      allow on-line data visualization and storage.

PMID- 1367274
TI  - Studies on the production of lipase from recombinant Staphylococcus carnosus.
AB  - Production of lipase from recombinant Staphylococcus carnosus pLipPS1 was studied
      in standard stirred tank bioreactors. Only low lipase activity was obtained under
      conventional operating conditions, i.e., moderate to high stirring speeds and
      aeration rates for keeping the dissolved oxygen concentration at high levels.
      Additional targetted experiments indicated that the reason for the observed low
      lipase activity is lipase inactivation due to surface forces and shear stress at
      the gas/liquid interface. Therefore, a cultivation strategy is proposed that
      minimizes gas/liquid interfacial area and maximizes the driving concentration for
      O2 mass transfer by controlling the dissolved oxygen to low values by gentle
      stirring and low aeration rates. Thus, high lipase activities can be obtained
      even in larger scale standard stirred tank bioreactors.

PMID- 1367275
TI  - Molecular cloning and characterization of the recA gene of Methylomonas clara and
      construction of recA deficient mutant.
AB  - The recA gene of the methylotrophic bacterium Methylomonas clara has been
      isolated from a genomic library by hybridization with the Escherichia coli recA
      gene. Its complete nucleotide sequence consists of 1029 bp encoding a polypeptide
      of 342 amino acids. Nucleotide sequence analysis of the M. clara recA gene
      revealed extensive homologies to recA genes from E. coli and Pseudomonas
      aeruginosa. Part of the physiological activity of the M. clara RecA protein has
      become evident in that E. coli recA mutant HB101 is complemented. The cloned recA
      gene has been modified in vitro by site-specific mutagenesis and by insertion of
      a kanamycin-resistance gene cassette into the recA coding sequence. M. clara recA
      mutants were obtained by replacement of the active recA gene by an in-vitro
      inactivated gene copy.

PMID- 1367277
TI  - Integrative transformation of the ascomycete Podospora anserina: identification
      of the mating-type locus on chromosome VII of electrophoretically separated
      chromosomes.
AB  - Protoplasts of wild-type strain s and a long-lived extrachromosomal mutant (AL2)
      of the ascomycete Podospora anserina were transformed using a plasmid (pAN7-1)
      which contains the hygromycin B phosphotransferase gene (hph) of Escherichia coli
      under the control of Aspergillus nidulans regulatory sequences. After optimizing
      the transformation procedure, transformation efficiencies of 15-21
      transformants/micrograms plasmid DNA were obtained. Using a second selectable
      vector (pBT3), which contains the beta-tubuline gene of a benomyl-resistant
      Neurospora crassa mutant, the co-transformation rate was determined. Southern
      blot hybridization experiments revealed that the transforming plasmid became
      integrated into the genome of the recipient either as a single copy or as
      multiple copies. In addition, the data from molecular as well as from classical
      genetic analyses indicated that in independent transformants vector integration
      occurred at different positions. The mitotic and meiotic stability of
      transformants proved to be dependent on the number of integrated plasmid copies.
      Genetic analyses revealed a transformant in which the integrated vector is
      closely linked to the mating-type locus. Fractionation of whole chromosomes by
      pulsed field gel electrophoresis and subsequent hybridization of the immobilized
      DNAs against radiolabelled vector sequences indicated the largest of seven
      chromosomes as the chromosome containing the integrated vector and thus the
      mating-type locus.

PMID- 1367276
TI  - Secretion of active truncated CD4 into Escherichia coli periplasm.
AB  - A truncated molecule containing the first 183 amino acid residues of the HIV-1
      receptor, CD4, was made by periplasmic secretion in Escherichia coli. The signal
      sequence from the E. coli proteins OmpA, PhoA, or OmpF was fused to the truncated
      CD4, under the control of either the trp or the lac promoter. The processed
      material secreted into the periplasm reacted with monoclonal antibodies and
      exhibited binding activity to the HIV-1 envelope protein gp120. Not all of the
      processed product was recovered in the periplasm by osmotic shock, suggesting
      that either the material aggregated in the periplasm or, during secretion, the
      molecule assumed some transient conformation that interfered with its
      translocation across the inner membrane. A mutation in prlA (a gene involved in
      secretion) increased the level of processing, suggesting that secretion of a
      heterologous protein in E. coli can be optimized by manipulating the host
      secretion apparatus.

PMID- 1367279
TI  - Designing the optimal oligo.

PMID- 1367278
TI  - Growth rate control in fed-batch cultures of recombinant Saccharomyces cerevisiae
      producing hepatitis B surface antigen (HBsAg).
AB  - A recombinant Saccharomyces cerevisiae producing hepatitis B surface antigen
      (HBsAg) exhibited growth-associated product formation. By controlling the medium
      feed rate, based on the calculated amount of medium required for 1 h, a constant
      specific growth rate was obtained in the range of 0.12-0.18 h-1. In order to
      prolong the exponential growth phase, the medium feed rate was increased
      exponentially. A fed-batch cultivation method based on the production kinetics of
      batch culture enhanced HBsAg production ten times more than in batch culture. The
      reason for the increase can be explained by the fact that the production of HBsAg
      is expressed as an exponential function of time when the specific growth rate is
      controlled to a constant value in growth-associated product formation kinetics.
      In the scale-up of this culture to 91, the specific growth rate could also be
      maintained constant and the HBsAg production trend was similar to that in a 1-1
      culture. However, ethanol accumulation occurred at a late stage in fed-bach
      culture. Ethanol produced was not reutilized and inhibited further cell growth.

PMID- 1367280
TI  - Life support systems for nanotechnology.

PMID- 1367281
TI  - Stabilizing protein products: coming in from the cold.

PMID- 1367282
TI  - Biotechnology and intellectual property. Part 2: Microorganism deposit questions
      and agricultural biotechnology issues.

PMID- 1367283
TI  - The prospects for therapy with tumour necrosis factors and their antagonists.
AB  - Tumour necrosis factors (TNFs) alpha and beta are capable of causing dramatic
      necrosis of solid tumours. TNF-alpha has undergone clinical trials as an anti
      cancer drug. Finding a role for TNFs in the treatment of cancer will depend on
      suppressing severe side effects and targeting the drug. Conversely, due to the
      participation of TNFs in inflammatory responses, antagonists of TNF-alpha are
      being considered for the treatment of several conditions, especially septic
      shock.

PMID- 1367284
TI  - Human and mouse monoclonal antibodies by repertoire cloning.
AB  - Antibody repertoires, the wide range of antibody molecules produced by animals,
      can now be established in bacteria by cloning and expression of antibody genes.
      Beginning with immunized animals, antigen can be used to select, from the
      repertoire, clones which secrete specific monoclonal antibody. In the future,
      immunization may become unnecessary. The method may provide a general route,
      which has so far eluded biotechnologists, to human monoclonal antibodies.

PMID- 1367285
TI  - Effect of NGF-2 on the survival of chick sensory ganglion neurons in vitro.
AB  - The biological activity of NGF-2, the third member of the NGF family, was
      investigated. Conditioned medium of COS cells transfected with expression plasmid
      for human NGF-2 cDNA promoted the survival of sensory neurons from dorsal root
      ganglia (DRG), and nodose ganglia (NG). Supernatant of mock transfected COS cells
      was less effective for the survival of DRG neurons and ineffective for the
      survival of NG neurons. These results suggest that NGF-2 is a novel neurotrophic
      factor whose biological activity is distinct from NGF.

PMID- 1367286
TI  - Properties of a cell line (MEG-01SSF) of human megakaryoblastic leukemia cells.
AB  - MEG-01SSF cells were prepared from MEG-01S by conditioning in a chemically
      defined, serum-free medium. The cells grew well in the medium and required
      transferrin for growth. Doubling time was about 20 hours. The cells retained
      GpIIb/IIIa as a marker of megakaryocytes and transferrin receptors on the cell
      surface. Some of the cells in the stationary phase of growth produced platelet
      like particles, which bore characteristic microtubule rings.

PMID- 1367287
TI  - Rapid PCR-cloning of full-length mouse immunoglobulin variable regions.

PMID- 1367288
TI  - Postbiosynthesis modification: human growth hormone and insulin precursors.

PMID- 1367289
TI  - Yeast fermentation processes for insulin production.

PMID- 1367290
TI  - Nucleic acid and protein blotting.

PMID- 1367291
TI  - A comparison of PVDF and pure nitrocellulose membranes for protein blotting
      applications.

PMID- 1367293
TI  - The hybridization oven: an evaluation for use in routine DNA profiling.

PMID- 1367292
TI  - Receptor-specific serum-free cell attachment using a highly stable engineered
      protein polymer.

PMID- 1367294
TI  - Safe control of supernatants in the laboratory.

PMID- 1367295
TI  - A system for immuno and nucleic transfers.

PMID- 1367296
TI  - Downstream processing: key to slashing production costs 100 fold.

PMID- 1367298
TI  - What the U.S. biopharmaceutical industry wants.

PMID- 1367297
TI  - Peptide synthesis gets friendly.

PMID- 1367299
TI  - FDA: biotech friend or foe?

PMID- 1367300
TI  - Aqueous two-phase extraction in bioseparations: an assessment.

PMID- 1367301
TI  - New perspectives on catalytic antibodies.
AB  - This review will give examples of the structure-function relationships used in
      the design of catalytic antibodies, including not only ligand or hapten-based
      approaches but also recent developments in the generation of catalytic antibodies
      through protein engineering. Last, a thermodynamic analysis is presented, which
      confirms that some antibodies do indeed catalyze their transformations by
      stabilizing transition states.

PMID- 1367302
TI  - The functional expression of antibody Fv fragments in Escherichia coli: improved
      vectors and a generally applicable purification technique.
AB  - We have previously demonstrated that the expression of fully functional Fv and
      Fab fragments in E. coli is possible by the simultaneous secretion of both chains
      to the periplasm. To increase production levels and facilitate engineering and
      random mutagenesis, we improved our previous vectors by introducing a resident
      repressor gene and a filamentous phage origin. We also developed a new
      purification strategy based on immobilized metal ion chromatography, with which a
      single-chain Fv fragment can be purified to homogeneity in a single step. We
      investigated the most efficient tail constructions and found that only a minimal
      structural change of three additional C-terminal amino acids is necessary. This
      modification has no deleterious effect on in vivo transport and folding or
      antigen affinity.

PMID- 1367304
TI  - Making monoclonals in microbes.

PMID- 1367303
TI  - Heterologous gene expression in Hansenula polymorpha: efficient secretion of
      glucoamylase.
AB  - We have introduced the glucoamylase gene (GAM1) from Schwanniomyces occidentalis
      into the genome of the methylotrophic yeast Hansenula polymorpha to study the
      potential of this organism as a host for high-level expression of a heterologous
      gene encoding a secretory protein. Transformants of H. polymorpha containing GAM1
      under control of the formate dehydrogenase (FMD) promoter are stable and
      efficiently secrete an active glucoamylase that is faithfully processed and
      modified. Yields of up to 1.4g/l of active enzyme were obtained at cell densities
      of 100-130 grams dry weight per liter.

PMID- 1367305
TI  - Payer pressure: the emerging force in drug development.

PMID- 1367306
TI  - The German Genetic Engineering Act.

PMID- 1367307
TI  - Assaying cytokines.

PMID- 1367308
TI  - Predicting the solubility of recombinant proteins in Escherichia coli.
AB  - We have studied the cause of inclusion body formation in Escherichia coli grown
      at 37 degrees C using statistical analysis of the composition of 81 proteins that
      do and do not form inclusion bodies. Six composition derived parameters were
      used. In declining order of their correlation with inclusion body formation, the
      parameters are charge average, turn forming residue fraction, cysteine fraction,
      proline fraction, hydrophilicity, and total number of residues. The correlation
      with inclusion body formation is strong for the first two parameters but weak for
      the last four. This correlation can be used to predict the probability that a
      protein will form inclusion bodies using only the protein's amino acid
      composition as the basis for the prediction.

PMID- 1367309
TI  - Piezoelectric cell growth sensor.
AB  - We have developed a reusable piezoelectric sensor that enables rapid
      characterization of cell viability and response to cell-affecting agents. This is
      accomplished via a novel polymer transduction principle that involves reaction of
      a pH-sensitive amphoteric polymer with metabolically generated acid. Subsequent
      adhesion of the protonated polymer to the transducer surface causes a decrease in
      the sensor resonant frequency corresponding to the cell metabolic rate. This
      disclosure provides the first example of a piezoelectric sensor capable of
      detecting metabolic responses of viable cells. The sensor provides real-time
      measurement of cell metabolism and division rates, and antibiotic sensitivity.
      This technology provides the basis for an advanced piezoelectric sensor that does
      not require immobilized biological receptors and can be miniaturized without
      compromising signal-to-noise factors.

PMID- 1367310
TI  - High-level expression of tetanus toxin fragment C in Pichia pastoris strains
      containing multiple tandem integrations of the gene.
AB  - We have used the methylotrophic yeast, Pichia pastoris, to express high levels of
      tetanus toxin fragment C, a potential subunit vaccine against tetanus. In high
      biomass fermentations fragment C was induced to 27% of total cell protein or
      about 12 g/l of culture. The purified protein was as effective as native fragment
      C in immunizing mice. In order to optimize fragment C production, we have
      examined the parameters affecting foreign gene expression in Pichia. The level of
      expression was found to be largely independent of the site of chromosomal
      integration of the gene (AOX1 or HIS4), the type of integrant (insertion or
      transplacement), and the methanol utilisation phenotype of the host strain (Mut+
      or Muts). The most important factor in obtaining high levels was the presence of
      multiple integrated copies of the fragment C expression cassette. Multicopy
      clones could be isolated from transformations using DNA fragments targeted for
      single-copy transplacement into the chromosome. These multicopy transformants
      were surprisingly stable over multiple generations during growth and induction in
      high cell density fermentations. Analysis of chromosomal DNA from these clones
      suggests that they arose by circularization of the transforming DNA fragment in
      vivo followed by multiple insertion into the chromosome via repeated single
      crossover recombination, in addition to the expected transplacement event. We
      have found this to be a general phenomenon and have used these multicopy
      "transplacement" clones to obtain high-level expression of several other foreign
      genes in Pichia.

PMID- 1367311
TI  - A novel synthetic method for hybridoma cell encapsulation.
AB  - We report here what we believe is the first example of the encapsulation of
      hybridoma cells within a synthetic polymer by a simple gelation with dissolved
      cations in water, and at room temperature. Two lines of hybridoma cells were
      encapsulated within calcium cross-linked polyphosphazene gel microbeads without
      affecting their viability or their capability to produce antibodies. Interaction
      of these gel beads with the positively-charged polyelectrolyte, poly(L-lysine),
      of 102-kD molecular weight, produced a semipermeable membrane that was capable of
      retaining the cell-secreted antibodies inside the beads. Cell density increased
      3.5-fold within 13 days concomitant with a 6.4-fold increase in antibody
      production. These synthetic membranes have the potential to aid in protein
      recovery schemes.

PMID- 1367312
TI  - Actinorhodin production by Streptomyces coelicolor and growth of Streptomyces
      lividans are improved by the expression of a bacterial hemoglobin.
AB  - Secondary metabolite production by Streptomyces is often highly sensitive to
      oxygen supply, which can be limiting in large-scale fermentations. In an attempt
      to improve oxygen utilization by the cells, we expressed a heterologous bacterial
      hemoglobin gene in Streptomyces coelicolor and Streptomyces lividans. Hemoglobin
      expression was demonstrated by immunoblot analysis and carbon monoxide binding
      activity. In batch fermentations run under reduced aeration, the expression of
      hemoglobin in S. coelicolor resulted in a ten-fold increase in specific yields of
      the aromatic polyketide, actinorhodin. Actinorhodin yields were also much less
      sensitive to aeration conditions in the hemoglobin-expressing strain. In
      addition, hemoglobin-expressing S. lividans cells grown under reduced aeration
      had higher final cell densities and exhibited greater oxygen consumption rates
      than non-expressing cells.

PMID- 1367313
TI  - High cell density cultivation of Escherichia coli at controlled specific growth
      rate.
AB  - A high cell density cultivation (HCDC) for growth of Escherichia coli in an
      especially designed glucose/mineral salt medium is proposed. The HCDC essentially
      starts as a batch process which is followed by a two-phase fed-batch cultivation.
      After unlimited growth at mu max = 0.45 h-1 in the batch part, growth was
      controlled at a reduced specific growth rate (mu = 0.11 h-1 less than mu max)
      over a period of 3 doubling times in which the biomass concentration increased
      from 12 to 95 g 1(-1) (phase 1 of fed-batch cultivation). Control of growth (mu)
      was realized by a PO2 control loop (by variation of glucose feeding) and a mu
      control loop (by variation of agitation speed N) while the actual mu was
      calculated from the off-gas composition. If the agitation rate cannot be
      increased anymore the mu controller is switched off (end of phase 1). In the
      following phase 2, mu declines, however, the still acting pO2 (glucose)
      controller guarantees sufficient O2 supply till the end of the cultivation with a
      biomass concentration of 110 g 1(-1) (dry mass). The proposed HCDC suppresses
      generation of inhibitory by-products and the high yield coefficients indicate the
      economy of the process.

PMID- 1367314
TI  - Biotin formation by recombinant strains of Escherichia coli: influence of the
      host physiology.
AB  - Strains of Escherichia coli were transformed with different plasmids bearing the
      gene clusters bioXWF and bioDAYB isolated from the Gram positive bacterium
      Bacillus sphaericus. These genes encode for the enzymes involved in the metabolic
      pathway which synthesizes biotin from the precursor pimelic acid. Transformed E.
      coli strains were grown in bioreactors to reach a biomass of 18 g l-1 cell dry
      weight in 1 litre batch culture with substrate feeding and approximately 50 g l-1
      in 10 l fed batch culture. Improved yields of total vitamers and biotin formed in
      these processes were achieved after a comparative analysis of different culture
      conditions, medium compositions, host strains and expression systems. Production
      of 27 mg l-1 of biotin and 200 mg l-1 of vitamers was achieved in 1 litre batch
      culture. Using a 10-1 fed batch process, biotin and vitamer concentrations
      reached maximum values of 45 mg l-1 and 350 mg l-1, respectively.

PMID- 1367315
TI  - Physico-chemical characterization of the main factors affecting the mode of
      action of liver alcohol dehydrogenase immobilized on nylon tubing.
AB  - Alcohol dehydrogenase (ADH) from horse liver (EC 1.1.1.1), cross-linked through
      the bifunctional reactive glutaraldehyde, onto nylon tubing was immobilized (35
      micrograms cm-2 internal surface of nylon tubing). ADH inactivation kinetics of
      the immobilized enzyme are of first order (t1/2 = 84.3 h, k = 8.2 x 10(-3) h-1 at
      5 degrees C; t1/2 = 2.6 h, k = 0.26 h-1 at 50 degrees C). The activity versus pH
      profile points to a smaller effect of pH on the activity of the enzyme, which is
      the case of ADH in solution, explicable on the basis of limitations to proton
      diffusion towards/from the support. A limiting effect to free external diffusion
      of the substrate (products) towards/from the support was observed; this effect
      seems to determine the effective kinetic behaviour of immobilized ADH.

PMID- 1367316
TI  - DNA sequence of a Salmonella-specific DNA fragment and the use of oligonucleotide
      probes for Salmonella detection.
AB  - Hybridization specificity of a 1.8-kb HindIII DNA fragment isolated from
      Salmonella typhimurium by a molecular cloning technique was confirmed by colony
      hybridization with 327 Salmonella isolates of various serotypes and 56 non
      Salmonella isolates including Enterobacteriaceae closely related to Salmonella,
      such as Escherichia coli, Klebsiella, Citrobacter and Shigella. It was found that
      this 1.8-kb DNA fragment was highly specific for all the Salmonella isolates
      tested. The DNA sequence of this 1.8-kb fragment was then determined by the
      dideoxynucleotide chain termination method. According to this DNA sequence, six
      oligonucleotide fragments ranging from 17- to 26-mer were then chemically
      synthesized and tested for their hybridization specificities. Results show that
      three of the six oligonucleotide fragments are highly specific for all 327
      Salmonella strains tested and can be used as probes for the specific detection of
      Salmonella in foods or other samples.

PMID- 1367318
TI  - Secondary metabolite biosynthesis in cultured cells of Catharanthus roseus (L.)
      G. Don immobilized by adhesion to glass fibres.
AB  - Suspension-cultured cells of Catharanthus roseus (L.) G. Don were immobilized on
      glass fibre mats and cultivated in shake flasks. The highly-aggregated
      immobilized cells exhibited a slower growth rate and accumulated reduced levels
      of tryptamine and indole alkaloids, represented by catharanthine and ajmalicine,
      in comparison to cells in suspension. The increased total protein synthesis in
      immobilized cells suggests a diversion of the primary metabolic flux toward
      protein biosynthetic pathways and away from other growth processes. In-vitro
      assays for the specific activity of tryptophan decarboxylase (TDC) and tryptophan
      synthase (TS) suggest that the decreased accumulation of tryptamine in
      immobilized cells was due to reduced tryptophan biosynthesis. The specific
      activity of TDC was similar in immobilized and suspension-cultured cells.
      However, the expression of TS activity in immobilized cells was reduced to less
      than 25% of the maximum level in suspension-cultured cells. The reduced
      availability of a free tryptophan pool in immobilized cells is consistent with
      the reduced TS activity. Reduced tryptamine accumulation, however, was not
      responsible for the decreased accumulation of indole alkaloids in immobilized
      cells. Indole alkaloid accumulation increased to a similar level in immobilized
      and suspension-cultured cells only after the addition of exogenous secologanin to
      the culture medium. The addition of tryptophan resulted in increased accumulation
      of tryptamine, but had no effect on indole alkaloid levels. Reduced biosynthesis
      of secologanin, the monoterpenoid precursor to indole alkaloids, in immobilized
      cells is suggested. Immobilization does not appear to alter the activity of
      indole alkaloid biosynthetic enzymes in our system beyond, and including,
      strictosidine synthase.

PMID- 1367320
TI  - Genetic manipulation enquiry--the way ahead.

PMID- 1367319
TI  - Novel ion-exchangers for the chromatographic purification of biopolymers-
      chemistry and column technology.

PMID- 1367321
TI  - The commercialization of biotechnology: important aspects of technology
      licensing.

PMID- 1367317
TI  - The screening of selected microorganisms for use as models of mammalian drug
      metabolism.
AB  - Fifty fungi and two Streptomyces species were screened for their ability to
      metabolise the probe substrates aminopyrine, diazepam, testosterone, theophylline
      and warfarin. The metabolism of the 14C-labelled substrates by whole growing
      cells was compared with that by rat liver microsomes using TLC-autoradiography.
      Testosterone, warfarin and diazepam were readily metabolised by most
      microorganisms, and aminopyrine and theophylline were only metabolised by a few.
      A relationship between substrate lipophilicity and number of microorganisms able
      to biotransform the substrate was observed, lipophilic substrates being favoured
      for metabolism, analagous to mammalian cytochrome P-450. A wide variety of
      metabolites were produced by the screened cultures, with a significant number co
      chromatographing with mammalian metabolites. Most microorganisms appeared to
      exhibit cytochrome P-450-type oxidative reactions such as hydroxylation and N
      demethylation, similar to mammalian hepatic microsomal cytochrome P-450 systems.

PMID- 1367322
TI  - Opportunities in New Zealand for biotechnology process development and contract
      research. The Biotechnology Group of DSIR Industrial Development, New Zealand.

PMID- 1367323
TI  - Recovery and purification of polysaccharides from microbial broth.
AB  - Current industrial practice to recover extracellular microbial polysaccharides
      from the broth usually requires dilution to permit cell removal followed by
      precipitation, typically using alcohol. This paper presents a discussion on the
      solvent precipitation of xanthan and the results of research performed to
      investigate the behaviour of xanthan solutions during membrane processing using a
      microporous membrane. Using crossflow microfiltration, flux rates of up to 120
      L/m2h were achieved for pure xanthan solutions, with complete rejection of the
      polysaccharide by the membrane. The thin film model underpredicted flux for
      xanthan solutions. In fact, flux was independent of xanthan concentration up to
      20-25 g/L, and strongly dependent on crossflow velocity. Considerable benefits in
      terms of purification and reduced solvent requirements can be obtained by the use
      of an intermediate crossflow microfiltration step during xanthan recovery.

PMID- 1367325
TI  - Monitoring the centrifugal recovery of recombinant protein inclusion bodies.
AB  - The industrial processing of proteins expressed as insoluble inclusion bodies
      employs a reasonably standard sequence of unit operations. One of these is
      centrifugation, which serves to concentrate the inclusion bodies after disruption
      of the host microorganism, and also separates the inclusion bodies from other
      cellular debris. Monitoring the performance of the centrifuge is essential if
      excessive product and hence financial loss is to be avoided and a reasonable
      separation obtained. The analytical disc centrifuge may be used to monitor the
      centrifugation. This instrument returns the sample size distribution with high
      resolution and without fouling. By obtaining size distributions of the centrifuge
      feed, supernatant and concentrate, the fractional collection efficiency of the
      centrifuge may be determined as a function of the Stokes diameter, and a mass
      balance constructed.

PMID- 1367324
TI  - A single step method for the solubilization and refolding of recombinant protein
      from E. coli inclusion bodies.
AB  - Expression of recombinant porcine growth hormone (rpGH) in E. coli cells resulted
      in the accumulation of the rpGH within inclusion bodies (IBs). The IBs were
      solubilized and the rpGH refolded in a single step using a cationic surfactant, N
      cetyl pyridinium chloride (CPC; C21H38ClN) in the absence of reducing agents. No
      additional dialysis or rapid dilution steps of the solubilizing agent were
      required to obtain a 30% yield of refolded and oxidized rpGH monomer at protein
      concentrations of up to 15-20 mg/mL. In contrast, the refolding in vitro of rpGH
      in the absence of CPC resulted in the formation of significant amounts of higher
      molecular weight aggregate at the expense of the biologically active monomer. The
      fluorescence spectrum of the purified refolded rpGH was indistinguishable from
      that of biologically active, pituitary derived porcine GH and reverse-phase HPLC
      analysis of the purified rpGH showed similar retention times to that of pituitary
      GH. It is likely that the use of cetylpyridinium chloride is generally applicable
      to the simplified high yield recovery of biologically active recombinant proteins
      from IBs.

PMID- 1367326
TI  - Continuous flow centrifugation.

PMID- 1367327
TI  - Analytical biotechnology: applications for downstream processing.

PMID- 1367328
TI  - Biochemical and physiological characterization of the efrotomycin fermentation.
AB  - An efrotomycin fermentation was characterized through physical, chemical and
      biochemical studies. Growth of the actinomycete, Nocardia lactamdurans occurred
      during the first 50 h of the fermentation cycle at the expense of glucose,
      protein, and triglycerides. The initiation of efrotomycin biosynthesis was
      observed when glucose dropped to a low concentration. Upon glucose depletion,
      cell growth ceased and a switch in the respiratory quotient occurred. Efrotomycin
      biosynthesis was supported by the utilization of soybean oil and starch. Analysis
      of triglyceride metabolism showed that no diglycerides or monoglycerides
      accumulated during the fermentation. The activity of extracellular enzymes
      (lipase, protease, and amylase) increased during the cell growth phase and
      decreased significantly after 150 h. The concentrations of DNA, tetrahydro
      vitamin K2 (a membrane component), and free amino acids in the supernatant
      increased dramatically late in the fermentation cycle (225 h), indicating massive
      cell lysis. During this same time period, a reduction in cellular respiratory
      activity and efrotomycin biosynthesis were observed.

PMID- 1367330
TI  - Impact of present and future regulations on bioremediation.
AB  - Innovative treatment technologies are in increasing demand to clean up the
      nation's existing environmental contamination. There also are mounting pressures
      for industry to minimize the production or generation of hazardous pollutants.
      Bioremediation is a viable, cost-effective treatment option for both field
      remediation and treatment in enclosed systems. The use of innovative treatment
      technologies is largely regulatory driven. Over the last two decades, at least a
      dozen Federal environmental statutes have been enacted and hundreds of
      regulations implemented to control releases of pollutants into the air, water and
      on land. These statutes not only have created markets for the use of treatment
      technologies, they also may regulate some aspect of the application of that
      technology. Regarding bioremediation, four statutes should be reviewed to
      determine if compliance is necessary before employing microorganisms in the field
      or in enclosed systems. This paper summarizes the Federal statutes (i.e., the
      Toxic Substances Control Act (TSCA); the Resource Conservation and Recovery Act
      (RCRA); the Comprehensive Environmental Response, Compensation and Liability Act
      (CERCLA); and the Federal Plant Pest Act (FPPA], and regulations that may impact
      the bioremediation industry; outlines potential markets for bioremediation that
      are being driven by regulations; and highlights, within the regulatory framework,
      promising applications for the bioremediation of hazardous wastes.

PMID- 1367331
TI  - Evaluation of a new turbidimeter design incorporating a microprocessor-controlled
      variable pathlength cuvette.
AB  - A microprocessor-controlled, variable pathlength turbidimeter was designed,
      constructed, and its operation verified and accuracy determined using formazin as
      a turbidity standard. The turbidimeter was also characterized with the
      fermentation broths of Saccharomyces cerevisiae and Escherichia coli. The range
      of turbidities quantified using the instrument spanned from 70 to 1,000
      Nephlometric Turbidity Units, with a measurement accuracy between 2% and 11% of
      the instrument's full-scale reading. The precision of the instrument was
      determined to be 0.077%. The turbidimeter was used to continuously monitor the
      biomass concentration of an Escherichia coli fermentation and provided
      instantaneous concentration estimates which corresponded with gravimetrically
      determined biomass concentrations to within 12%.

PMID- 1367329
TI  - Transcriptional organization and regulation of the nosiheptide resistance gene in
      Streptomyces actuosus.
AB  - The nosiheptide resistance gene (nshR) and a putative regulatory gene (nshA) are
      found together on a 2326 bp BamHI-PstI DNA fragment isolated from Streptomyces
      actuosus ATCC 25421. The putative regulatory gene, nshA, situated upstream from
      the nosiheptide resistance gene in the 2326 bp DNA fragment, contains apparent
      DNA-binding and RNA-binding domains. Interruption of nshA in the chromosome of S.
      actuosus alters nosiheptide production, suggesting that nshA is involved in
      regulation of nosiheptide biosynthesis. Two transcription initiation sites were
      found upstream of nshA as demonstrated by high-resolution S1 nuclease mapping. A
      weak transcription start site for nshR was found which initiated transcription
      from the first nucleotide of the open reading frame. Although a stem-loop
      structure with apparent termination activity was found between nshA and nshR,
      readthrough of transcription between nshA and nshR was demonstrated by S1
      nuclease mapping of the 3' terminus of the nshA transcript. Time-course S1
      experiments of the three promoters (nshA-pl, nshA-p2, nshR-p) indicated highly
      regulated differential expression of the promoters. nshA-p2 is a strong,
      constitutive promoter whereas 30% of the total nshA-p1/p2 transcript reads
      through the terminator and into the nshR gene, accounting for more than half of
      the total steady-state nshR transcript. The implications of the regulation of
      nshA and nshR gene expression, as well as the expression of two other linked
      genes, are presented.

PMID- 1367332
TI  - Construction of a sucrose-fermenting bakers' yeast incapable of hydrolysing
      fructooligosaccharides.
AB  - Fructooligosaccharides stimulate the growth of intestinal bifidobacteria which
      are related to the favorable health and nutrition of humans and other animals.
      Since the efficient amount of fructooligosaccharide for an adult human is
      relatively large (about 5 g per day), its addition to daily foods like bakery
      goods might be beneficial. However, commercial Bakers' yeast hydrolyses
      fructooligosaccharides by the action of invertase encoded in SUC genes and
      ferments the resulting monosaccharides. According to the findings that strains
      carrying the MAL-constitutive gene and lacking the SUC gene fermented sucrose and
      not fructooligosaccharide, we constructed a sucrose-fermenting strain, YOY920,
      incapable of hydrolysing fructooligosaccharide, by cross-breeding a baking strain
      and a laboratory strain. In a molasses medium, the cell yield of YOY920 was
      comparable to that of a baking strain FSC6001, and much higher than that of the
      non-sucrose-fermenting strains. Although fructooligosaccharide inhibited the
      dough leavening ability of YOY920, white bread containing fructooligosaccharide
      could be produced in the defined dough formula using the new strain.

PMID- 1367333
TI  - A method for the preparation of coimmobilizates by adhesion using
      polyethylenimine.
AB  - A method has been described for obtaining coimmobilizates by the simultaneous
      binding of glucose oxidase to the cell and the enzyme-bound cell to cotton thread
      through adhesion using polyethylenimine (PEI). Glucose oxidase was found to
      adsorb onto PEI-coated yeast cells from a water suspension. The desorption
      observed at higher ionic strength could be obviated by cross-linking with 2%
      glutaraldehyde for 2 min. The enzyme-bound yeast cells could then be immobilized
      by adhesion on cotton thread. The coimmobilizate could be reused for over 10
      batches without appreciable loss in activity.

PMID- 1367334
TI  - Temperature-gradient electrophoresis. A thermodynamic probe provides information
      on the structure of DNA and proteins.

PMID- 1367335
TI  - Multiple DNA sample processing by agarose gel electrophoresis.

PMID- 1367336
TI  - Are media just media? (Part I).

PMID- 1367337
TI  - Triterpenoid saponins discovered between 1987 and 1989.
AB  - Triterpenoid saponins isolated and characterized from various sources are
      reviewed. The recent techniques used in their isolation and structure elucidation
      are discussed. A compilation of the triterpenoid saponins isolated during the
      period from 1987 to mid-1989, together with their occurrence, available physical
      data and spectroscopy used for their characterization is included. The biological
      activities of the triterpenoid saponins are also covered.

PMID- 1367338
TI  - Four major saponins from Solidago canadensis.
AB  - Four new bisdesmosidic saponins each containing eight carbohydrate units were
      isolated from Solidago canadensis. GC, GC-MS, FABMS analysis and mainly the use
      of 2D NMR techniques allowed their identification as bayogeninglycosides
      (canadensissaponins 1-4) 3-O- [beta-D-glucopyranosyl-(1----3)-beta-D
      glucopyranosyl]-28-O-[alpha-L- rhamnopyranosyl-(1----3)-beta-D-xylopyranosyl-(1--
      -4)-[beta-D- xylopyranosyl-(1----3)]-alpha-L-rhamnopyranosyl-(1----2)-[beta-D-
      apio-D-furanosyl-(1----3)]-beta-D-6-deoxyglucopyranosyl- (1----]-bayogenin; -(1--
      -2)-[beta-D-apio-D-furanosyl-(1----3)]-ara- binopyranosyl-(1----]-bayogenin; 
      [alpha-L-rhamnopyranosyl-(1----3)]-beta- D-6-deoxyglucopyranosyl-(1----]
      bayogenin and - [alpha-L-rhamnopyranosyl- (1----3)]-arabinopyranosyl-(1----]
      bayogenin.

PMID- 1367339
TI  - Quinovic acid glycosides from Uncaria guianensis.
AB  - From the bark of Uncaria guianensis, two new quinovic acid glycosides, quinovic
      acid 3 beta-O-beta-D-quinovopyranoside and quinovic acid 3 beta-O-beta-D
      fucopyranosyl-(27----1)-beta-D-glucopyranosylester, have been isolated, in
      addition to known quinovic acid 3 beta-O-[beta-D-glucopyranosyl-(1----3)-beta-D
      fucopyranosyl]-(27----1)- beta-D-glucopyranosylester and quinovic acid 3 beta-O
      beta-D-fucopyranoside. Their structures were elucidated by spectral and chemical
      studies.

PMID- 1367340
TI  - Triglucosylation on the biotransformation of (+)-menthol by cultured cells of
      Eucalyptus perriniana.
AB  - Cultured cells of Eucalyptus perriniana biotransformed (+)-menthol to its
      gentiobioside and triglucoside [2,6-di-O-(beta-D-glucopyranosyl)-beta-D
      glucopyranoside]. The structures of these compounds were determined by means of
      NMR techniques.

PMID- 1367341
TI  - 12-Hydroxy steroidal glycosides from the caudex of Yucca gloriosa.
AB  - The structures of the new steroidal saponins (tentatively named YS-XI, -XII and 
      XIII) have been isolated from the caudex of Yucca gloriosa and characterized as 3
      O-beta-D-glucopyranosyl-(1----2)-beta-D-galactopyranosyl 5 beta- (25R)-spirostan
      3 beta, 12 beta-diol, 3-O-beta-D-glucopyranosyl-(1----2)- [beta-D-glucopyranosyl
      (1----3)]-beta-D-glucopyranosyl 5 beta- (25R)-spirostan-3 beta, 12 beta-diol and
      3-O-beta-D-glucopyranosyl-(1----2)- beta-D-galactopyranosyl 5 beta-(25R)
      spirostan-2 beta,3 beta,12 beta-triol, respectively.

PMID- 1367342
TI  - Flavonol triglycosides containing galactose in tea.
AB  - The isolation and structural elucidation of new quercetin and kaempferol
      triglycosides from Camellia sinensis is described. Their structures were
      determined as quercetin and kaempferol 3-glucosyl(1----3) rhamnosyl(1---
      6)galactosides. The content of quercetin glucosylrhamnosylgalactoside ranged
      between 0 and 87 mg per 100 g, and that of the kaempferol homologue between 0 and
      119 mg per 100 g dry wt.

PMID- 1367343
TI  - Bromodeoxyuridine labeling and flow cytometric identification of replicating
      Saccharomyces cerevisiae cells: lengths of cell cycle phases and population
      variability at specific cell cycle positions.
AB  - An immunofluorescent staining procedure has been developed to identify, with flow
      cytometry, replicating cells of Saccharomyces cerevisiae after incorporation of
      bromodeoxyuridine (BrdUrd) into the DNA. Incorporation of BrdUrd is made possible
      by using yeast strains with a cloned thymidine kinase gene from the herpes
      simplex virus. An exposure time of 4 min to BrdUrd results in detectable labeling
      of the DNA. The BrdUrd/DNA double staining procedure has been optimized and the
      flow cytometry measurements yield histograms comparable to data typically
      obtained for mammalian cells. On the basis of the accurate assessment of cell
      fractions in individual cell cycle phases of the asynchronously growing cell
      population, the average duration of the cell cycle phases has been evaluated. For
      a population doubling time of 100 min it was found that cells spend in average 41
      min in the replicating phase and 24 min in the G2+M cell cycle period. Assuming
      that mother cells immediately reenter the S phase after cell division, daughter
      cells spend 65 min in the G1 cell cycle phase. Together with the single cell
      fluorescence parameters, the forward-angle light scattering intensity (FALS) has
      been determined as an indicator of cell size. Comparing different temporal
      positions within the cell cycle, the determined FALS distributions show the
      lowest variability at the beginning of the S phase. The developed procedure in
      combination with multiparameter flow cytometry should be useful for studying the
      kinetics and regulation of the budding yeast cell cycle.

PMID- 1367344
TI  - Flow cytometry and cell cycle kinetics in continuous and fed-batch fermentations
      of budding yeast.
AB  - Cell size distributions, obtained either as protein distribution by flow
      cytometry or as cell volume distribution by a Coulter counter, give relevant
      information about the growth conditions of populations of budding yeast
      Saccharomyces cerevisiae. We have previously found a good correlation between
      these distributions and the growth rate in continuous cultures (Ranzi et al.,
      Biotechnol. Bioeng. 1986, 28, 185-190). We now present determinations of the
      protein distributions and cell volume distributions during different fed-batch
      fermentations performed with a simple on/off controller. Since during the fed
      batch fermentation a true steady state is not obtained, the distributions
      continuously change with time, but nevertheless we observed a good correlation
      between the average of both distributions and the actual growth rate. The
      behavior of the cell size distributions can be interpreted on the basis of a two
      threshold cell cycle model in which both the critical protein content at budding
      (Ps) and the critical protein content for cell division (Pm) are differently
      modulated by the growth rate. Additional findings will be presented showing that
      this model can be used to successfully explain the insurgence and the maintenance
      of oscillatory states in continuous cultures.

PMID- 1367346
TI  - A microperifusion system with environmental control for studying insulin
      secretion by pancreatic tissue.
AB  - A continuous flow reactor (perifusion system) was fabricated and tested for
      measuring the kinetics of insulin secretion from isolated pancreatic islets of
      Langerhans in response to step changes in the glucose concentration and oxygen
      partial pressure in the perfusate flowing around the islets. The system was
      capable of making rapid changes in perfusate glucose concentration and pO2, had
      rapid dynamic response for measuring the change in insulin secretion rate as a
      result of these changes in perfusate, and was suitable for studying very small
      volumes of tissue. Initial experiments with this system demonstrated that (1) the
      response of isolated rat islets to glucose stimulation was very fast, with the
      first phase peak occurring in as little as about 10 s, (2) bulk perfusate oxygen
      partial pressure levels of 30 mmHg or less reduced the second-phase insulin
      secretion rate in graded fashion, (3) the reduction in secretion rate began
      within 1 min following an oxygen partial pressure decrease, and (4) the reduction
      in secretion rate was reversible, with a burst of insulin secretion occurring
      during the first minute after partial pressure restoration.

PMID- 1367345
TI  - Block copolymer microdomains: a novel medium for enzymatic reactions.
AB  - Block copolymers exhibit the phenomenon of microdomain formation in pure states
      as well as in solutions. The microdomains vest the block copolymer assemblies
      with the intriguing characteristics of microheterogeneous media. We demonstrate
      that this microheterogeneity in hydrophobic-hydrophilic block copolymer systems
      can be exploited for immobilizing enzymes and to carry out enzymatic reactions.
      Examples involving cholesterol oxidase and horseradish peroxidase are provided
      here. The observed changes in the enzymatic activity in block copolymer
      microdomains from that in the aqueous media are interpreted in terms of the
      hydrophobicity of the reaction microenvironment. The block copolymer microdomains
      are simple to generate, well defined, and easily reproducible. Therefore, they
      hold significant potential as media for enzymatic biosynthetic reactions when the
      substrates or the reaction products are water insoluble.

PMID- 1367347
TI  - The evolution of the word 'biotechnology'.

PMID- 1367348
TI  - The coming of age of glycobiology.

PMID- 1367349
TI  - Multienzyme systems obtained by gene fusion.
AB  - The preparation of artificial bi- and polyfunctional enzymes by gene fusion
      appears to have great potential in enzyme technology. Their purification is
      facilitated compared with that of their naturally occurring counterparts and they
      exhibit favourable enzyme kinetics. Applications can be found in biochemical
      analysis, enzyme process technology and metabolic engineering.

PMID- 1367350
TI  - High performance capillary electrophoresis.
AB  - The application of recombinant-DNA methods for the production of therapeutic
      proteins has, over the past decade, driven the development of new technology for
      the analysis and characterization of biological molecules. High performance
      capillary electrophoresis (HPCE) has generated enormous interest among
      biochemists, analytical chemists and chromatographers, and is emerging as an
      extremely high-resolution separation technique, that may rival high performance
      liquid chromatography (HPLC) in its efficiency and breadth of application.

PMID- 1367351
TI  - Gene transfer in staphylococci: stimulation and suppression by antibacterial
      agents.

PMID- 1367352
TI  - 1991 Bio/Technology Compensation Survey.

PMID- 1367353
TI  - Patent patterns in biotech.

PMID- 1367354
TI  - Stock offerings raise a staggering $1.7 billion.

PMID- 1367355
TI  - Wanted: companies to attack aging.

PMID- 1367356
TI  - Protein aggregation in vitro and in vivo: a quantitative model of the kinetic
      competition between folding and aggregation.
AB  - Protein aggregation is frequently observed as a major side-reaction of protein
      folding. We present quantitative models explaining the formation of aggregates
      during protein folding in vitro and in vivo on the basis of a kinetic competition
      between correct folding and aggregation reactions. Both models are in good
      agreement with experimental data. The model implies that, in vitro, the yield of
      native protein obtained upon refolding is determined by the rates of the
      competing first order folding and second order aggregation reactions. Therefore,
      a high protein concentrations aggregation dominates over folding and leads to the
      formation of insoluble protein. For in vivo protein synthesis, the model shows
      that the yield of native protein is only dependent on the rate of folding, on the
      rate of aggregation and on the rate of protein synthesis. In the cell, several
      mechanisms, including "folding helpers" seem to have evolved, which influence
      these processes and thereby prevent unproductive side reactions.

PMID- 1367357
TI  - High level expression of active human alpha-1-antitrypsin in the milk of
      transgenic sheep.
AB  - We describe the generation of five sheep transgenic for a fusion of the ovine
      beta-lactoglobulin gene promotor to the human alpha 1-antitrypsin (h alpha 1AT)
      genomic sequences. Four of these animals are female and one male. Analysis of the
      expression of h alpha 1AT in the milk of three of these females shows that all
      express the human protein at levels greater than 1 gram per liter. In one case
      initial levels exceeded 60 grams per liter and stabilized at approximately 35
      grams per liter as lactation progressed. Human alpha 1AT purified from the milk
      of these animals appears to be fully N-glycosylated and has a biological activity
      indistinguishable from human plasma-derived material.

PMID- 1367358
TI  - Generation of transgenic dairy cattle using 'in vitro' embryo production.
AB  - We have combined gene transfer, by microinjection, with 'in vitro' embryo
      production technology, enabling us to carry out non-surgical transfer, to
      recipient cows, of microinjected embryos that have been cultured from immature
      oocytes. Using this approach, we have established 21 pregnancies from which 19
      calves were born. Southern blot analysis proved that in two cases the
      microinjected DNA had been integrated in the host genome.

PMID- 1367359
TI  - Development of a recombinant baculovirus expressing an insect-selective
      neurotoxin: potential for pest control.
AB  - Recombinant nuclear polyhedrosis viruses (NPVs) expressing insect-selective
      toxins, hormones, or enzymes could enhance their insecticidal properties. We have
      constructed a recombinant, polyhedrin-positive Autographa californica NPV (AcNPV)
      that is orally infectious and expresses an insect-selective toxin (AaIT),
      isolated from the scorpion Androctonus australis, under the control of the p10
      promoter. Bioassays with the recombinant baculovirus on 2nd instar larvae of
      Heliothis virescens demonstrated a significant decrease in the time to kill (LT50
      88.0 hours) compared to wild-type AcNPV (LT50 125 hours). Production of AaIT was
      confirmed by western blot analysis of larval hemolymph from infected H.
      virescens, and bioassays with larvae of Sarcophaga falculata.

PMID- 1367360
TI  - Secretion of active bovine somatotropin in Escherichia coli.
AB  - We have expressed a chimeric protein, comprising the LamB secretion signal
      sequence fused to mature bovine somatotropin (bST), in Escherichia coli. Plasmid
      constructs with the recA promoter showed significant protein accumulation prior
      to induction and cell lysis occurred after induction. In contrast, the lacUV5
      promoter was tightly regulated. With the lacUV5 promoter, temperature and inducer
      concentration had significant effects on the total amount of recombinant protein
      produced and the fraction processed to mature bST. Quantitation of bST from shake
      flask cultures showed that 1-2 micrograms/ml/OD550 could be released from the
      periplasm by osmotic shock. N-terminal sequence analysis of the purified protein
      indicated that the majority of the secreted bST was correctly processed. The bST
      present in the osmotic shock fraction was judged to be correctly folded by
      comigration with oxidized methionyl-bST standard on a non-reducing polyacrylamide
      gel and activity in a bovine liver radioreceptor assay. These results provide a
      rapid method to produce bST for use in structure-function studies.

PMID- 1367361
TI  - Rapid clonal growth measurements at the single-cell level: gel microdroplets and
      flow cytometry.
AB  - We describe a new, general method for rapidly measuring clonal growth of large
      numbers of individual members of a cell population. This method is based on
      microculture of individual colony-forming units in gel microdrops (GMDs; here
      agarose; 20 to 90 mu in diameter), which are sufficiently robust to be handled
      much like cells, and diffusionally transparent for molecules of interest. Flow
      cytometry provides rapid measurements of GMD-entrapped microcolonies, and permits
      subpopulation analysis. Here the method is demonstrated with mammalian, fungal
      and bacterial species. Additional results illustrate rapid determination of a
      drug-resistant subpopulation in a mixed species sample, and nutrient sensitivity
      for a murine hybridoma.

PMID- 1367362
TI  - Effects of fluid shear on immobilized enzyme kinetics.
AB  - There have been a number of reports concerning the damaging effects of shear on
      globular proteins in solution. Some recent work has indicated, however, that
      globular proteins in solution are relatively stable, but may be inactivated at
      air-liquid interfaces during shearing. This study investigated the effects of
      fluid shear on immobilized enzyme activity. Immobilized enzyme reactors were
      built to operate with the enzyme immobilized at the boundary of a fluid flow
      field. Two different enzymes, penicillinase and lactate dehydrogenase, were
      covalently bound to the interior surface of nylon tubes. Fluid shear rate was
      changed by varying the flow rate of substrate (reactant) solution through the
      tube, and fluid shear stresses were increased by increasing the viscosity of the
      recirculating solution. There were no observed effects of fluid shear on
      immobilized penicillinase or lactate dehydrogenase activity at shear rates of up
      to 10,350 s-1 or at shear stresses of up to 73 Pa.

PMID- 1367363
TI  - Studies on improved techniques for immobilizing and stabilizing penicillin
      amidase associated with E. coli cells.
AB  - A method for catalyst development has been suggested for immobilizing whole E.
      coli cells containing penicillin amidase. Conventional methods have limitations,
      such as permeation of substrate and product through cellular membranes, leaching
      of protein and other cellular components into the reaction phase, lower specific
      activity compared to immobilized enzyme system, etc. The whole cell
      immobilization technique has been optimized for different process parameters. The
      most suitable conditions for this process were pH, 4.25; cell concentration,
      3.75%; concentration of glutaraldehyde, 1.5%; level of bovine serum albumin as
      additional support, 2 mg ml-1. The reaction was continued for 2 h. The granular
      catalyst has good mechanical strength, low protein leachability, and high
      retention of penicillin amidase activity.

PMID- 1367364
TI  - Production of cell mass and pertussis toxin by Bordetella pertussis.
AB  - The cultivation of Bordetella pertussis affects production of pertussis toxin and
      biomass. Comparison of batch mode, chemostat operation and pHstat-turbidostatic
      control showed that productivities for the continuous process were greater than
      that for the batch operation. Continuous operation in balanced growth at the
      maximum specific growth rate, provided by the pHstat, resulted in the maximum
      specific production rate. Because of the strong association of pertussis toxin
      synthesis and cell growth, the concentration of toxin in the effluent of the
      continuous processes was greater than the maximum obtained in the batch
      bioprocess. An expanded Luedeking-Piret model of product formation kinetics fits
      the observed chemostat data and demonstrates that the production of pertussis
      toxin from the culture of B. pertussis is predominantly growth associated.

PMID- 1367365
TI  - Aspects of biotechnology in a united Germany.

PMID- 1367366
TI  - High density culture of anchorage-dependent animal cells by polyurethane foam
      packed-bed culture systems.
AB  - Monkey kidney cells (Vero) and Chinese hamster ovary cells (CHO-K1) attached to
      the internal surface of polyurethane foam (PUF) and grew to a high cell density
      (1.1 x 10(8) cells/cm3 PUF and 4.2 x 10(7) cells/cm3 PUF, respectively) in a PUF
      plates packed-bed culture system. This density of Vero cells was twice that
      obtained previously with a PUF-particles packed-bed culture system. A maximum
      cell density of 6.7 x 10(7) cells/cm3 culture vessel volume was obtained in a PUF
      disc packed-bed culture of Vero cells. From the cell density of CHO-K1, growing
      in a monolayer on the surface of PUF and a petri dish, per bulk volume of PUF, we
      estimated that a surface area to volume ratio of PUF plates effective for cell
      growth was about 109 cm2/cm3.

PMID- 1367367
TI  - Some aspects of hybridoma cell cultivation.
AB  - Two hybridoma cell lines were cultivated in an indirectly aerated 10-1 reactor in
      batch, fed-batch and continuous (perfusion) operations and in spinner flasks. The
      medium in the reactor was sampled either by an aseptic cross-flow filtration
      module integrated into a loop or by an in-situ tubular filter. The glucose
      concentration was monitored by an on-line flow injection analyser and the ammonia
      concentration by an ion-selective electrode. Since the membrane transmission of
      the high-molecular components decreased during cultivation, the product, a
      monoclonal antibody, was enriched in the reactor. During cultivation, the
      concentrations of cells, viable cells, glucose, lactase, acetate, citrate,
      ammonia, urea, amino acids, proteins, and monoclonal antibodies were determined
      off-line. The specific growth rate, specific production, and consumption rates of
      the medium components were influenced considerably by the medium composition,
      especially by the type and amount of serum used.

PMID- 1367368
TI  - Structured model for cell growth and enzyme production by recombinant Escherichia
      coli.
AB  - A structured cell model has been developed to describe the cultivation of
      recombinant Escherichia coli K12 with multicopy plasmid under the control of a
      lambda PR-promoter and a temperature-sensitive lambda cI 857 repressor. The
      model, based on measurements of a batch culture in a stirred tank reactor, allows
      statements to be made on the time variation of intracellular processes. Based on
      cell regulation, the substrate transfer into the cell was considered to be the
      rate-limiting step for substrate utilization. The model describes substrate
      utilization, cell growth, and product formation by means of a system of time
      dependent, coupled, and partly non-linear differential equations. The solution of
      these equations allows calculation of the time variation of the concentrations of
      substrates (glucose and amino acids), dissolved oxygen and cells in the broth as
      a function of time and the process parameters.

PMID- 1367369
TI  - Simulation of cell growth, substrate consumption and product formation with
      recombinant Escherichia coli.
AB  - The growth of recombinant Escherichia coli, consumption of different amino acids
      and glucose as well as fusion protein formation are simulated by a structured
      mathematical model and compared with measurements carried out in a stirred tank
      reactor under well-controlled conditions. The model parameters were identified
      based on the variation in cell concentration, particular amino acids, and glucose
      as well as intracellular products during cultivation. The dependence of the model
      parameters on cultivation time and culture conditions (temperature, medium
      composition, dissolved oxygen concentration) are discussed.

PMID- 1367370
TI  - Monitoring survival and gene transfer in soil microcosms of recombinant
      Escherichia coli designed to represent an industrial production strain.
AB  - A genetically engineered microorganism (GEM) was designed to exemplify bacterial
      strains used for the production of biological material in industry. The
      recombinant DNA was located on a safety plasmid (pUC19). Survival and persistence
      of the GEM and its recombinant DNA (rDNA) was determined in soil microcosms by
      using different monitoring methods, including the polymerase-chain reaction, to
      amplify and detect the specific rDNA. Depending on nutritional status, both the
      GEM and its rDNA had disappeared within 16 (amended soil) or 28 days (non-amended
      soil) with a limit of detection of 5 cells/g soil and 20 fg DNA/g soil.

PMID- 1367371
TI  - Cephamycin C biosynthesis in Streptomyces cattleya: nitrogen source regulation.
AB  - The production of cephamycin C by Streptomyces cattleya varies with the use of
      asparagine, glutamine or ammonium as nitrogen sources. Hydroxylase and expandase
      activities were demonstrated for the first time with this species. A study of the
      biosynthetic regulation of these enzymes by two different nitrogen sources,
      glutamine and asparagine, was carried out. Asparagine proved to be a better
      nitrogen source, both for enzymatic biosynthesis and production of cephamycin C.
      Moreover, an excess of asparagine in the culture environment provokes,
      simultaneously, a reduction in cephamycin C production and a decrease in the
      biosynthesis of expandase and hydroxylase.

PMID- 1367372
TI  - A comparison of animal and plant cells.

PMID- 1367373
TI  - Technical improvements for flow karyotyping by standard FACS 440 flow cytometer.
AB  - Chromosomal DNA measurements represent the most accurate methodology for the
      quantitative analysis of human karyotype. A modified FACS 440 signal collection
      is described here. The FSC signal voltage coming from the optical bench has been
      split in two equal parts by a T-connector placed at the preamplifier entrance.
      The side scatter channel that is not employed during chromosome analysis has been
      used for the half-FSC signal. This modification allowed the contemporary use of
      FSC signal both for gating and analysis leading to a better discrimination of
      background, and therefore to a more accurate definition of sorting windows.

PMID- 1367374
TI  - Passive release of monoclonal antibodies from hybridoma cells.
AB  - Evidence is presented for the passive release of monoclonal antibodies (MCAB)
      from hybridoma cells grown in either batch or continuous-flow culture. This
      release is promoted at room temperature. Passively released MCAB is
      indistinguishable from that released by actively growing cells, as judged by SDS
      polyacrylamide gel electrophoresis. The significance of these observations in
      relation to the continuous culture of hybridoma cells is discussed. Maximum MCAB
      content of TB/C3 hybridoma cells is about 55pg per cell, any additional MCAB
      produced is secreted.

PMID- 1367376
TI  - High density cultivation of BSK cells on sintered alumina ceramic foam support.
AB  - A perfusion system which utilizes a porous ceramic core has been tested for the
      cultivation of transformed BHK cells which produce human transferrin. A design is
      presented in which cells are immobilized within the porous ceramic particle and
      are fed by continuous perfusion of batch liquid medium. It was found that more
      than 5 x 10(9) BHK cells could be supported within the 40 mL ceramic matrix, a
      ten-fold increase in cell density per unit surface area over the standard roller
      bottle cultures or a five-fold increase in volumetric cell density over
      suspension cultures. The cell specific productivity of human transferrin was
      similar to that observed in suspension culture. The system offer the advantages
      of significant reduction in serum requirements and the potential for scale-up.

PMID- 1367375
TI  - Karyotypic stability of serum-free mouse embryo (SFME) cells.
AB  - Mouse embryo cultures derived in serum-containing medium undergo growth crisis or
      senescence after fewer than 20 population doublings, followed by the emergence of
      genetically altered, polyploid 'immortalized' cells capable of growing
      indefinitely. Serum-free mouse embryo (SFME) cells, derived in medium in which
      serum is replaced with growth factors and other supplements, do not exhibit
      growth crisis or gross chromosomal aberrations when cultured for well over 100
      population doublings and display other unique properties. We examined culture
      conditions and physiological factors affecting karyotypic stability in long term
      cultures of SFME cells derived from several mouse strains. Cloning SFME cells
      consistently isolated colonies with altered karyotype, even when the clones were
      derived from parent cultures with no karyotypic alterations. After 140-200
      population doublings in vitro, the percentage of SFME cells showing hyperdiploidy
      or structural chromosomal abnormalities increased, although the modal chromosome
      number remained diploid. SFME cells transformed with molecularly cloned oncogenes
      did not show alterations in karyotype beyond that expected from the clonal
      origins of these cells, indicating that malignant transformation of SFME cells
      does not result in general karyotypic instability.

PMID- 1367377
TI  - Cell cycle dependency of monoclonal antibody production in asynchronous serum
      free hybridoma cultures.
AB  - The cell cycle kinetics of F3(B6) mouse hybridoma was examined by
      immunocytochemical staining of bromodeoxyuridine incorporated into the DNA of
      exponentially growing cells in three different cultures: one supplemented with
      10% fetal bovine serum and two adapted to serum-free media, TABIES and BITES. The
      serum-free cultures, particularly the BITES, had longer cycling times and higher
      specific antibody production rate. Both observations were correlated to the
      prolongation of the G1 phase traverse time and substantiated with a starvation
      blocking experiment.

PMID- 1367378
TI  - Purification of immunoglobulin production stimulation factor II alpha derived
      from Namalwa cells.
AB  - An immunoglobulin production stimulating factor (IPSF) in human lymphoblastoid
      Namalwa cells was purified by the serial use of ammonium sulfate fractionation,
      hydrophobic interaction chromatography and gel filtration, and named IPSF-II
      alpha. IPSF-II alpha was estimated as a 112 KD protein composed of a 40 KD
      polypeptide and two 36 KD polypeptides. The 36 KD protein extracted from SDS
      polyacrylamide gel showed IPSF activity, but not the 40 KD protein. The IPSF
      activity was reasonably stable in alkaline but unstable in acidic solution and
      heat-unstable. In a serum-free medium, IPSF-II alpha stimulated IgM production of
      human-human and mouse-mouse hybridomas 4-15 and 2-fold, respectively, although
      its growth stimulatory effect on hybridomas was negligible. The factor did not
      stimulate IgG production in either human or mouse hybridomas in the same serum
      free medium. These results suggested that IPSF-II alpha was a new cellular factor
      for stimulating IgM productivity of hybridomas.

PMID- 1367379
TI  - Three-dimensional culture of human tumor cells under standardized medium
      conditions.
AB  - The 3-dimensional culture of human tumor spheroids under standardized medium
      conditions may reveal information on specific biological parameters that could be
      masked in serum-supplemented media. Spheroids derived from human tumor cells are
      growth retarded in media free of serum. Ex-Cyte IV is a substance derived from
      human blood that can be used to improve growth in tissue culture. In this study
      the growth of spheroids from four different human tumor cell lines was studied
      when grown in medium free of serum, medium supplemented with varying
      concentrations Ex-Cyte IV, and medium supplemented with foetal calf serum (FCS).
      The parameters used for comparisons were growth rate, growth enhancement,
      clonogenicity and cell cycle distribution. The four cell lines showed different
      growth rates in serum-free medium, which were increased to different extents when
      Ex-Cyte IV or FCS were added. The growth enhancing effect induced by Ex-Cyte IV
      was differently concentration dependent for each cell line. The clonogenicity of
      cells grown as spheroids in serum-free medium was lower than in spheroids grown
      in supplemented media. There was no difference in clonogenicity between the
      differently supplemented media. All four cell lines responded to growth in serum
      free medium with a drop in the S-phase and G2M phase. The present study provides
      a novel approach to the study of human tumor cells in 3-dimensional culture under
      defined conditions. The human serum derived substance Ex-Cyte IV may provide a
      method to obtain information on specific biological parameters that could be
      masked in serum-supplemented media.

PMID- 1367380
TI  - A simple method for in situ freezing of anchorage-dependent cells including rat
      liver parenchymal cells.
AB  - We developed a simple method for freezing anchorage-dependent cells, including
      primary cultured rat liver parenchymal cells, without detaching the cells from
      the culture dish. The method consists of preculture of the cells to confluence,
      changing the growth medium to a conventional freezing medium, packaging in a
      container, and storage at -80 degrees C. After thawing and changing the freezing
      medium to regular growth medium, cell growth was nearly identical to that of
      cells freshly seeded into a new dish.

PMID- 1367382
TI  - Immunologically active polysaccharides of Arnica montana cell cultures.
AB  - From the nutrition medium of Arnica montana cell cultures two homogeneous
      polysaccharides, an acidic arabino-3,6-galactan-protein with mean Mr of 100,000
      and a neutral fucogalactoxyloglucan with mean Mr of 22,500 have been isolated by
      DEAE-Sepharose CL-6B and Sephacryl S-400 column chromatography. Their structures
      were elucidated mainly by methylation analysis, partial acidic and enzymatic
      hydrolysis and 13C NMR spectroscopy. The fucogalactoxyloglucan shows a pronounced
      enhancement of phagocytosis in vivo. The arabino-3,6-galactan-protein displays a
      strong anticomplementary effect and stimulates macrophages to excrete the tumour
      necrosis factor (TNF alpha).

PMID- 1367381
TI  - Stimulation of proliferation and immunoglobulin production of human-human
      hybridoma by various types of caseins and their protease digests.
AB  - We have studied the effect of such milk proteins as caseins, lactalbumin, and
      lactoglobulin, on proliferation and immunoglobulin production of human-human
      hybridoma HB4C5 cells. It was found that alpha-, beta-, and kappa-caseins
      stimulated both proliferation and IgM product ion of human-human hybridoma HB4C5
      cells, while the activities of alpha-lactalbumin and beta-lactoglobulin were
      negligible. To localize the active sites of these caseins, effect of protease
      treatments on the activities were examined. When caseins were digested with
      trypsin, casein digests stimulated proliferation of the hybridoma, but not their
      IgM production. When kappa-casein was digested with chymosin and fractionated to
      p-kappa-casein and glycomacropeptide, both fragments stimulated proliferation of
      the cells, but only p-kappa-casein fragment stimulated IgM production. These
      results indicate that kappa-casein has at least two proliferation stimulating
      sites and an IgM production stimulating site in the p-kappa-casein region.

PMID- 1367383
TI  - Distribution and characterization of diglycosyldiacylglycerol isomers with
      different anomeric configuration in higher plants.
AB  - The novel diglycosyldiacylglycerol (DGDG), galactosyl(beta 1----6)
      galactosyl(beta 1----3')-diacylglycerol (B isomer), present in Adzuki beans was
      found to be distributed together with the well-known galactosyl(alpha 1----6)
      galactosyl(beta 1----3')-diacylglycerol (A isomer), in all (10) of the higher
      plants examined. The highest levels were found in leguminous seeds were the
      amounts were always less than 33% of the total DGDG of mature seeds. The highest
      proportion of the B isomer was found in Adzuki bean seed DGDG (26-33%), with the
      lowest in pea seed DGDG (2%). The amounts of the B isomer in DGDG of Adzuki and
      kidney beans cotyledons were almost equal to those in mature seeds. Immature
      seeds and hypocotyls of three kinds of beans also contained the B isomer in small
      amounts compared with the mature beans, while only trace amounts of the isomer
      was found in other organs such as leaves, stems, pods, roots and generative
      organs of plants, except for root from kidney beans. The molecular species
      composition of the principal diacylglycerol moieties in the A and B isomers of
      DGDG were found to be significantly different among several plant seeds, although
      the component diacylglycerol species were qualitatively similar to each other.

PMID- 1367384
TI  - Structural features of the sulphated polysaccharide from a green seaweed,
      Spongomorpha indica.
AB  - A sulphated heteropolysaccharide, [alpha]D +59 degrees, was isolated from a green
      seaweed, Spongomorpha indica, by extraction with ammonium oxalate. The polymer is
      composed of arabinose, xylose, galactose and glucose in the ratio
      8.9:1.0:12.0:1.0. Studies showed that the polysaccharide is a complex and
      multilinked polymer containing arabinose in both furanose and pyranose forms. The
      core of the polysaccharide is composed of 1,4-linked galactose units. The
      arabinofuranose units are present as non-reducing end units, as well as jointed
      through 1,3- and 1,2-linkages. The majority of the arabinopyranose units are
      joined through 1,4-linkages. Xylose is present as a branch terminating unit.
      Glucose is joined through 1,4-linkages. Both arabinose and galactose carry
      branches. Sulphate groups are present on some of the arabinose units at C-2 and
      on some of the galactose units at C-2 and C-3.

PMID- 1367385
TI  - Agaveside C, a steroidal glycoside from Agave cantala.

PMID- 1367386
TI  - Phenylpropanoid and iridoid glycosides from Pedicularis striata.
AB  - A new phenylpropanoid glycoside, pedicularioside A, and five known glycosides,
      acteoside, isoacteoside, decaffeoylacteoside, echinacoside and 8-acetylharpagide,
      were isolated from whole plants of Pedicularis striata. On the basis of spectral
      and chemical evidence, pedicularioside A was shown to be 1'-O-beta-D-(3,4
      dihydroxy-beta-phenyl)-ethyl-4'-O-caffeoyl-beta-D -apiosyl-(1----3')-alpha-L
      rhamnosyl-(1----6')-glucopyranosi de.

PMID- 1367387
TI  - Antibodies in plants.

PMID- 1367388
TI  - Myeloma based expression system for production of large mammalian proteins.

PMID- 1367389
TI  - Binding contracts: antibody engineering.

PMID- 1367390
TI  - From sphygmomanometers to synchrotrons: the progress of protein structure
      determination.

PMID- 1367391
TI  - Biotechnology and intellectual property. Part 1: Patenting in biotechnology.

PMID- 1367392
TI  - CD4-targeted immune intervention: a strategy for the therapy of AIDS and
      autoimmune disease.
AB  - The cell-surface antigen CD4 plays a pivotal role in the class II MHC-restricted
      response of specific T lymphocytes, and serves as the major receptor of human
      immunodeficiency virus (HIV). The recent elucidation of CD4 function in
      physiological and pathological conditions has improved prospects for CD4-targeted
      immune therapy by facilitating the design of therapeutic strategies aimed at
      blocking CD4 function, delivering immunosuppressive signals via this receptor
      molecule, or selectively depleting CD4+ cells.

PMID- 1367393
TI  - Expression of human antithrombin III in the cellular slime mould Dictyostelium
      discoideum.
AB  - In order to test the biotechnological potential of the cellular slime mould
      Dictyostelium discoideum the cDNA coding for human antithrombin III was expressed
      in this microorganism. The 1392-bp antithrombin III cDNA was fused to the N
      terminal coding part of the D. discoideum actin 6 gene. In constructs carrying
      this artificial N-terminal coding region only low amounts of antithrombin III
      were detected. However, constructs from which all actin coding nucleotides were
      removed produced significant amounts of anti-thrombin III, most of which was
      secreted into the culture broth. Stationary cultures (1.5 x 10(7) cells/ml) of
      certain stable transformants accumulated up to 1.0 microgram antithrombin III/ml
      culture medium within 24 h. The recombinant protein has a slightly smaller
      molecular weight in sodium dodecyl sulphate-polyacrylamide gels than authentic
      plasma antithrombin III and it is glycosylated, as determined by concanavalin A
      labelling.

PMID- 1367395
TI  - Incorporation and activation of a membrane-bound enzyme in bilayers of liposomes.
AB  - The effects of lipid composition and fluidity of lipid bilayers on incorporation
      and activation of membrane-bound D-fructose dehydrogenase are described in this
      study. The incorporation of the enzyme into bilayers of small unilamellar
      vesicles (SUV) made of several phospholipids resulted in enzyme activation with
      magnitudes higher than that observed in the presence of Triton X-100, indicating
      that this higher activation is due to lipid-protein interaction. The activity was
      highest in the presence of SUV formed by the addition of 10% DL-alpha
      dipalmitoylphosphatidylethanolamine to L-alpha-dimyristoylphosphatidylcholine,
      which resulted in eightfold higher activation compared with that of the enzyme in
      its free state. This activation did not appear to be due to the degree of
      incorporation of the enzyme, indicating that incorporation is distinct from the
      activation event. Thus, it is probably the lipid environment that leads to higher
      activation of the enzyme. A break in the Arrhenius plot of the activity of the
      membrane-bound enzyme at temperatures close to the phase transition of the
      phospholipid implies that changes in the physical state of the lipid bilayer
      influence the enzyme activity. Furthermore, immobilization of D-fructose
      dehydrogenase, previously adsorbed to SUV, on urethane prepolymer also resulted
      in about eightfold higher activation than that of the free enzyme.

PMID- 1367394
TI  - Molecular analysis of a Bjerkandera adusta lignin peroxidase gene.
AB  - A cDNA clone, lambda LPO-1, encoding a major lignin peroxidase from the
      basidiomycete Bjerkandera adusta was isolated and characterized. The nucleotide
      sequence of lambda LPO-1 predicts a mature protein consisting of 349 amino acids
      with a molecular weight of 37,225 preceded by a signal peptide of 23 amino acid
      residues. We have also cloned and sequenced the gene encoding lignin peroxidase
      from B. adusta. Comparison of these sequences reveals a lignin peroxidase gene
      structure consisting of 1,116 bp of protein-encoding DNA that is interrupted by
      four intervening sequences. The putative eukaryotic regulatory sequence, a TATA
      box, is present at position -75 relative to the translational initiation codon.
      Amino acid sequence homology between the coding regions of lambda LPO-1 and of
      the lignin peroxidase cDNA clone lambda ML-1 from Phanerochaete chrysosporium is
      61%.

PMID- 1367396
TI  - Degradation of 3,4-dichloroaniline in synthetic and industrially produced
      wastewaters by mixed cultures freely suspended and immobilized in a packed-bed
      reactor.
AB  - Degradation of 3,4-dichloroaniline (34DCA) in aqueous solution by undefined
      cultures of free and immobilized cells was examined. Batch cultures of freely
      suspended cells and continuous degradation in a packed-bed reactor were studied
      using both synthetically concocted and industrially produced waste-waters. 34DCA
      was found to be degraded with a concomitant evolution of chloride ions into the
      bulk medium. The packed bed reactor with biomass immobilized on celite
      diatomaceous earth was found to be capable of degrading over 98% of the 34DCA
      present in a synthetically concocted inlet stream at a concentration of 250 mg l
      1. Residence times of less than 4 h were employed, giving an overall volumetric
      degradation rate for the packed bed of 90 mg l-1 h-1. The industrially produced
      waste-water contained, in addition to 34DCA, aniline, 4-chloroaniline, 2,3
      dichloroaniline (23DCA) and 3,4-dichloronitrobenzene. The biomass enriched on the
      synthetic 34DCA waste-water was found to be capable of degrading these compounds
      in addition to 34DCA with the exception of 23DCA. 34DCA degradation efficiencies
      of over 95% were obtained for the industrial waste-water at reactor residence
      times of 4.6 h, giving volumetric degradation rates of 24 mg l-1 h-1.

PMID- 1367397
TI  - Suppression of the degradation of recombinant human apolipoprotein E by a
      protease inhibitor obtained from fetal bovine serum in serum-free culture.
AB  - The recombinant human apolipoprotein E (Apo-E) produced by Chinese hamster ovary
      cells (CHO-322 cells) in serum free culture was degraded to 24K and 23K fragments
      that contained N-terminal amino acid. The degradation site of Apo-E to 24K
      fragment was between Arg180 and Leu181 and the C-terminal amino acid of 23K
      fragment was Gly169. In fetal bovine serum (FBS)-containing culture, the
      degradation was inhibited. However, in calf serum (CS) the inhibitory activity
      was not detected. Thus, we attempted the purification of the factor with this
      inhibitory activity from FBS. A protease inhibitor was purified to give a single
      peak from FBS by ammonium sulfate precipitation and combination of several column
      chromatographies. When this FBS-derived protease inhibitor (FBS-d-PI) was added
      to serum-free culture of CHO-322 cells, degradation of recombinant Apo-E to the
      24K and 23K fragments was dose-dependently suppressed and accumulation of intact
      Apo-E in culture supernatant was observed. FBS-d-PI was found to be a
      glycoprotein with relative molecular size of 75K daltons under reducing
      condition, and 85K daltons under nonreducing condition by SDS-PAGE. A complex of
      FBS-d-PI and a cellular protease was also detected in culture supernatant by
      western blot analysis using mouse monoclonal antibodies against FBS-d-PI.

PMID- 1367398
TI  - Serum-free medium for murine and human lymphoid and hybridoma cell lines.
AB  - We established a serum-free medium of low protein content (125 micrograms/ml) TYI
      100, consisting of three hormones and five growth factors for the growth of
      lymphoid and hybridoma cell lines. In TYI 100 medium, mouse and human hybridomas
      grew equally well as in RPMI 1640 supplemented with 10% fetal bovine serum (10%
      FBS) without adaptation to the serum-free medium. TYI 100 medium allowed several
      passages of mouse hybridoma lines and the total cell number was more than in 10%
      FBS. TYI 100 medium also supported growth of myelomas and anchorage dependent
      cell lines, Bowes and CHO, well. TYI 100 medium is composed of inexpensive
      supplements and is therefor applicable to large scale culture.

PMID- 1367399
TI  - Studies of serum-free medium for the generation of lymphokine-activated killer
      cells.
AB  - We examined a serum-free medium (designated as TYI 101) for the generation of
      lymphokine-activated killer (LAK) cells from human lymphocytes, regional lymph
      node lymphocytes (RLNL) and peripheral blood lymphocytes (PBL). TYI 101 medium
      consisted of, in addition to nutrient mixture, transferrin, insulin, fetuin,
      sodium selenite, 2-mercaptoethanol, o-phosphorylethanolamine, chick egg yolk and
      porcine kidney extract. These hormones were effective for supporting RLNL
      proliferation as assessed by (3H)-thymidine uptake. When human lymphocytes from
      two different sources were cultivated with recombinant interleukin 2 (rIL-2) in
      TYI 101 medium, LAK activity was generated. In cultures of PBL from a healthy
      donor, LAK cells were generated in TYI 101 medium as efficiently as in RPMI 1640
      medium supplemented with 10% human AB-type serum (RPMI-AB). In cultures of RLNL
      from lung cancer patients, LAK activity obtained in TYI 101 medium was about
      sixty-five percent of that in RPMI-AB. However, the addition of a small amount of
      AB-type serum improved the generation of LAK activity, LAK cell expansion, and
      cell viability in TYI 101 medium. We conclude that TYI 101 medium can be used for
      the generation of LAK cells from human lymph node lymphocytes with
      supplementation of none or only a reduced amount of human serum.

PMID- 1367400
TI  - Primary cell culture from embryos of the Japanese scallop Mizuchopecten
      yessoensis (Bivalvia).
AB  - Primary cell cultures obtained from embryos of Mizuchopecten yessoensis
      (Bivalvia) survived for four months. Although the number of cells progressively
      decreased during the cultivation, mitotic cells were observed both at the first
      stages and at the end. A possibility of growing marine invertebrates cells in
      long term primary culture is discussed.

PMID- 1367401
TI  - On-line monitoring of monoclonal antibody formation in high density perfusion
      culture using FIA.
AB  - An automated flow injection system for on-line analysis of proteins in real
      fermentation fluids was developed by combining the principles of stopped-flow,
      merging zones flow injection analysis (FIA) with antigen-antibody reactions. IgG
      in the sample reacted with its corresponding antibody (a-IgG) in the reagent
      solution. Formation of insoluble immunocomplexes resulted in an increase of the
      turbidity which was determined photometrically. This system was used to monitor
      monoclonal antibody production in high cell density perfusion culture of
      hybridoma cells. Perfusion was performed with a newly developed static filtration
      unit equipped with hydrophilic microporous tubular membranes. Different sampling
      devices were tested to obtain a cell-free sample stream for on-line product
      analysis of high molecular weight (e.g., monoclonal antibodies) and low molecular
      weight (e.g., glucose, lactate) medium components. In fermentation fluids a good
      correlation (coefficient: 0.996) between the FIA method and an ELISA test was
      demonstrated. In a high density perfusion cultivation process mAb formation was
      successfully monitored on-line over a period of 400 h using a reliable sampling
      system. Glucose and lactate were measured over the same period of time using a
      commercially available automatic analyser based on immobilized enzyme technology.

PMID- 1367402
TI  - Weaning of three hybridoma cell lines to serum free low protein medium.
AB  - A general weaning procedure is described which allowed a range of hybridomas to
      be weaned readily off serum without loss of antibody production. Initial work was
      carried out with one cell line only (SPO1 cells) and one serum substitute
      containing a final protein concentration of 40 mg l-1. The SPO1 cells were first
      adapted to a range of readily available basal media and then weaned off serum by
      a range of protocols. From this work an optimal weaning protocol and basal medium
      for weaning were determined. These were then used to wean the SPO1 cells and two
      other cell lines off serum with a second, protein free, serum substitute with
      varying concentrations of defined proteins added. All three cell lines
      investigated were readily weaned off serum by this protocol at protein
      concentrations as low as 1 mg l-1. No loss of antibody production was observed
      with any of the cell lines. The weaning procedure outlined in both simple and
      rapid and has been successfully adopted in our laboratory by relatively
      inexperienced cell culture technicians.

PMID- 1367403
TI  - Cross contamination associated with the use of multiwell culture plates for
      cytotoxicity assessment of volatile chemicals.
AB  - In vitro toxicity testing can involve technical problems due to the evaporation
      of volatile test chemicals. The cytotoxicity of two volatile chemicals (butanol
      and ethanol) has been assessed with neutral red assay in conventional microtiter
      plates. The non volatile DMSO chemical is used as a negative control. Under these
      conditions, an important cross contamination between test concentration groups
      has been observed. This affects cytotoxicity estimation which is overestimated.
      This cross contamination is prevented when special plates containing removable
      bars are used.

PMID- 1367404
TI  - A comparison of serum-free media for the support of in vitro mitogen-induced
      blastogenic expansion of cytolytic lymphocytes.
AB  - The high cost and potential dangers of including human AB serum in incubation
      media used to expand lymphocyte populations in vitro for adoptive immunotherapy
      have stimulated efforts to develop defined media which can support both the
      expansion and induction of lymphocytes with tumor cytolytic activity in the
      absence of serum. Lymphocyte proliferation following exposure to either PHA or
      the combination of phorbol 12,13-dibutyrate (PDBu) and the calcium ionophore,
      ionomycin, was evaluated. Although the media tested, X-Vivo 10, HB-104, AIM V,
      and HL-1, supported the generation of comparable levels of LAK activity after 3-5
      days incubation with 10(3) U human recombinant interleukin-2 (rIL-2)/ml, there
      were striking differences in the ability of each medium to support mitogenically
      stimulated lymphocytes in the absence of serum, with cells in AIM V and X-Vivo 10
      showing the highest levels of DNA synthesis. In long-term cultures (17 days) of
      blood MNC stimulated by PDBu and ionomycin, X-Vivo 10 and HB-104 yielded the
      greatest numbers of cells. The addition of 2% AB serum greatly enhanced the
      ability of each medium to support cell proliferation to equivalent maximum
      levels. The results indicate that while all four serum-free media were suitable
      for lymphocyte culture and support the development of LAK activity, they differ
      in their capacity to support expansion of lymphocyte populations in response to
      polyclonal mitogenic activation. This latter characteristic should be considered
      before choosing a particular serum-free formulation as its constituents may
      affect mechanistic interpretations regarding signal transduction events.

PMID- 1367405
TI  - Immunoglobulin production stimulating factor-II alpha (IPSF-II alpha) is
      glyceraldehyde-3-phosphate dehydrogenase like protein.
AB  - Amino acid sequence of the 36 KD protein which is the active subunit of
      immunoglobulin production stimulating factor-II alpha (IPSF-II alpha) derived
      from Burkitt's lymphoma Namalwa cells was analyzed for the 20 amino acids from N
      terminus. The N-terminal amino acid sequence of this protein coincided very
      closely with glyceraldehyde-3-phosphate dehydrogenase (GPD; EC 1.2.1.12) derived
      from various origins. Especially, it was completely homologous with that of human
      liver GPD. Several GPD's derived from human erythrocyte, rabbit muscle and
      Bacillus stearothermophilus also stimulated IgM production of hybridomas, as well
      as IPSF-II alpha. Conversely, IPSF-II alpha had GPD enzymic activity as strong as
      rabbit muscle and B. stearothermophilus, and stronger than human erythrocyte GPD.
      These results suggested that 36 KD subunit of IPSF-II alpha was a GPD, or GPD
      like protein. The level of mRNA for IgM was not enhanced by IPSF-II alpha in
      hybridoma cells, though the IgM productivity of the cell was remarkably
      stimulated by the protein, indicating that IPSF-II alpha does not stimulate
      immunoglobulin production by enhancement of transcription.

PMID- 1367407
TI  - 2,3,5-Triphenyl tetrazolium chloride (TTC) reduction as exponential growth phase
      marker for mammalian cells in culture and for myeloma hybridization experiments.
AB  - Triphenyl tetrazolium chloride in vitro reduction by cells produces a red
      formazan pellet which can be extracted and measured. We have shown that such
      reduction is associated with animal cell growth, and particularly with the
      specific growth rate, so the measurement of Triphenyl tetrazolium chloride
      reduction is proposed as a physiological marker of the exponential growth of
      cultured cells. Further application of this technique is shown using this Redox
      reaction for estimating plasmacytoma fusion potential for hybridoma cell line
      production.

PMID- 1367406
TI  - Erythropoietin gene expression in haemopoietic cell lines.
AB  - Erythropoietin (Epo) gene expression was studied in a number of different
      haemopoietic cell lines by in situ hybridization and Northern Blot analysis using
      a radioisotope-labelled monkey Epo DNA probe. A positive message was expressed by
      a human cell line, CM-S, derived from a patient with congenital hypoplastic
      anemia, and by a murine erythro-leukaemic cell line, clone 707, derived from the
      spleen of Friend virus-infected mice. No message was detected in two
      megakaryoblastic cell lines, and in a monocytic cell line, derived from a patient
      with acute monocytic leukaemia. These data may fit with the hypothesis of
      expression of Epo and other growth factors by haemopoietic cells through a
      mechanism of so-called autocrine secretion.

PMID- 1367408
TI  - DNA fingerprinting and the characterisation of cell lines.

PMID- 1367410
TI  - The role of nodulation genes in bacterium-plant communication.

PMID- 1367409
TI  - Improvement in the proliferative activity of human-human hybridomas at low cell
      density by transfection with bFGF gene.
AB  - Highly purified recombinant basic fibroblast growth factor (rbFGF) and acidic FGF
      (aFGF) stimulated the proliferation of human-human (h-h) hybridomas to the extent
      of over four-fold from a low cell density such as 1 x 10(3) cells per ml in a
      serum-free medium in 24-well plates. The stimulatory effect of rbFGF was also
      observed in various lymphoid cell lines. Expecting that FGF could be an autocrine
      growth factor, we introduced bFGF gene into a h-h hybridoma using an expression
      plasmid induced by dexamethasone. The transformed cells thus obtained, HPO-75.11
      bFGF-7, were able to grow well from a low inoculum density in a serum-free medium
      and antibody production was also increased when bFGF gene expression was induced.
      The transformed cells could grow at clonal density in a serum-free medium in 96
      well plates, though the original cells could not. We also obtained a more
      practical transfectant, HPO-75.29-H74, using a high-shear stress adapted clone as
      the recipient and an expression plasmid having bFGF gene under the control of
      metallothionein-I promoter. The HPO-75.29-H74 cells were capable of growing and
      producing human monoclonal antibody against hepatitis B virus surface antigen
      from an inoculum density of 1 x 10(3) cells per ml in an agitation vessel without
      addition of an inducer.

PMID- 1367411
TI  - Regulation of gene expression by epidermal growth factor.

PMID- 1367412
TI  - Machinery for protein import into chloroplasts and mitochondria.

PMID- 1367413
TI  - High-level expression of foreign genes in mammalian cells.

PMID- 1367414
TI  - Aromatic hydrocarbon degradation: a molecular approach.

PMID- 1367415
TI  - Employment of fibroblasts for gene transfer: applications for grafting into the
      central nervous system.
AB  - Genetic modification of primary skin fibroblasts offers a new approach to the
      focal delivery of deficient transmitter-specific enzymes (e.g., TH) or trophic
      substances (e.g., NGF) to the damaged or diseased CNS. Although fibroblasts are
      unable to provide anatomical corrections to defective neural connectivity, they
      can serve as biological pumps for the enzymes and growth factors in vivo. The
      capability of genetically engineered cells to ameliorate disease phenotypes in
      animal models of CNS disorders may ultimately results in the restoration of
      function. At this time, primary skin fibroblasts appear to be a convenient
      cellular population for the application of gene transfer and intracerebral
      grafting for the animal model of Parkinson's disease. It is now important for
      future investigations to provide data concerning the long-term stable expression
      of the transgene product (e.g., TH) following intracerebral implantation, as well
      as determining optimal conditions for the survival of primary cells grafted into
      the nervous system.

PMID- 1367416
TI  - Genetic manipulation of Bacillus thuringiensis insecticidal crystal protein genes
      in bacteria.

PMID- 1367417
TI  - Molecular biology of mating-type determination in Schizophyllum commune.

PMID- 1367418
TI  - Transgenic fish for aquaculture.

PMID- 1367419
TI  - Nuclear incorporation of [adenine 14C]NAD is altered by compounds which affect
      poly(ADP-ribose) formation.
AB  - The use of a DNA alkylating agent, which induces poly(ADP-ribose) formation, has
      been employed to study the incorporation of [adenine 14C]NAD into pea root
      meristem nuclei, which is a prerequisite for poly(ADP-ribose) synthesis. The
      incorporation of [adenine 14C]NAD is significantly reduced when the poly(ADP
      ribose)polymerase inhibitors, 7-methylxanthine and 3-methoxybenzamide are present
      and this incorporation is augmented when the DNA alkylating agent methyl
      methanesulfonate is added. Such information supports the hypothesis that poly(ADP
      ribose) may be involved in the cell cycle regulation of pea root meristem nuclei.

PMID- 1367420
TI  - Enhanced removal of Exxon Valdez spilled oil from Alaskan gravel by a microbial
      surfactant.
AB  - Remediation efforts for the oil spill from the Exxon Valdez tanker in Alaska have
      focused on the use of pressurized water at high temperature to remove oil from
      the beaches. We have tested a biological surfactant from Pseudomonas aeruginosa
      for its ability to remove oil from contaminated Alaskan gravel samples under
      various conditions, including concentration of the surfactant, time of contact,
      temperature of the wash, and presence or absence of xanthan gum. The results
      demonstrate the ability of the microbial surfactant to release oil to a
      significantly greater extent (2 to 3 times) than water alone, particularly at
      temperatures of 30 degrees C and above.

PMID- 1367421
TI  - The alpha-amylase gene as a marker for gene cloning: direct screening of
      recombinant clones.
AB  - We report the construction and use of a new system for the direct screening of
      recombinant clones after transformation. The system uses a Bacillus subtilis
      Escherichia coli shuttle vector that carries the B. subtilis structural gene for
      alpha-amylase. Insertion of foreign DNA into this gene results in a loss of
      amylolytic activity in the host cells that can be assayed using a simple and
      inexpensive staining procedure.

PMID- 1367422
TI  - Amperometric determination of ammonium ions with a microbial sensor.
AB  - A sensor for NH+4 ions has been developed, which consists of immobilized micro
      organisms (Bacillus subtilis, Pseudomonas aeruginosa, Trichosporon cutaneum) in
      combination with an electrochemical transducer. This sensor is based on the
      measurement of acceleration of respiration after addition of NH+4 in the presence
      of glucose. The physiological background of this signal and its connection with
      NH+4 ion uptake and/or metabolism is discussed. The response time of the sensor
      is about 5-10 s for NH+4 ions. A linearity was observed between 0.005 and 0.15
      mmol dm-3 NH+4 ions. The sensitivity of the sensor remained almost constant for
      12 days. The sensor was used to determine NH+4 ions in a microbial fermentation
      broth.

PMID- 1367424
TI  - Illegitimate recombination in Bacillus subtilis: a site-specific mechanism in the
      formation of plasmid pKBT1.
AB  - The Bacillus subtilis plasmid pKBT1, the product of in vivo recE4-independent
      recombinal events, contains segments derived from pUB110 and the B. subtilis
      chromosome. To determine whether the pUB110 sequence is intact in PKBT1, two 1 kb
      fragments, each containing a site at which chromosomal and pUB110 sequences are
      joined, were cloned and sequenced. Sequencing data revealed that: 1). An intact
      copy of pUB110 is present in pKBT1; 2) The apparent recombination sites were
      adjacent to the Bam HI-generated ends of pUB110 sequences; 3) pTL12-derived
      sequences from the original transforming DNA were limited to no more than 1 bp
      outside the Bgl II recognition sequence; 4) Recombination sites at both ends of
      pUB110 contain a 19 bp inverted repeat with 15 homologous nucleotides. These
      findings suggest a site-specific mechanism acting during in vivo formation of
      pKBT1.

PMID- 1367423
TI  - DNA sequence analysis of an abl-related gene in the blow fly, Calliphora
      erythrocephala.
AB  - The Ceabl locus is a member of a small family of abl-related sequences in C.
      erythrocephala. The catalytic, SH2 and SH3 domains of the Ceabl-encoded protein
      show greater than 75% sequence identity to vertebrate abl protein tyrosine
      kinases and greater than 95% identity to the D. melanogaster abl polypeptide.
      Ceabl diverges from the vertebrate proteins, however, at the extreme amino
      terminus, near the beginning of the vertebrate abl exon involved in differential
      splicing. The carboxyl region shows no detectable similarity to the vertebrate
      abl proteins, while identity to Drosophila abl falls to 55%. Regions conserved
      between the two dipteran genes revealed no strong similarities to other proteins
      in the Genbank and EMBL databases.

PMID- 1367425
TI  - Zinc finger structure of a ribosomal gene-specific transcription factor.
AB  - Xenopus transcription factor IIIA (TFIIIA) or TFIIIA mutants with internal
      deletions were expressed in E.coli, isolated from E.coli cell extracts, and
      identified by SDS PAGE and immunoblotting with rabbit antiserum against native
      TFIIIA. Specific DNA binding of intact or internally deleted TFIIIA was compared
      by analyzing their abilities to protect the internal control region (ICR) of the
      Xenopus 5S ribosomal RNA gene from DNase I digestion. Intact protein bound
      specifically to the entire ICR (+96 to +43). One TFIIIA deletion mutant,
      expressed from cDNA lacking the coding sequence for the putative fourth zinc
      finger protected the ICR from DNase I digestion from nucleotide positions +96 to
      +78. A second TFIIIA mutant resulting from fusion of putative zinc fingers 7 and
      8 protected the 5S gene ICR from positions +96 to +63. The regions of the protein
      comprising the N-terminal 3 fingers and N-terminal six fingers appear to be in
      contact with approximately 18 and 33 bp of DNA respectively on the 3' side of the
      5S gene ICR.

PMID- 1367426
TI  - Spin filter perfusion system for high density cell culture: production of
      recombinant urinary type plasminogen activator in CHO cells.
AB  - We have used a 20 liter stirred tank fermentor, equipped with a 127 mesh ethylene
      tetrafluoroethylene rotating screen for cell recycle, for the continuous
      production of recombinant single chain urokinase-type plasminogen activator (rscu
      PA) from Chinese hamster ovary (CHO) cells. Viable cell densities between 60 and
      74 million per ml were maintained at medium perfusion rates of 3.0 to 4.0
      fermentor volumes per day. Cells were retained by the 120 micron nominal opening
      filter through the formation of "clumped" cell aggregates of 200 to 600 microns
      in size, which did not foul the filter. In 31 days of culture, a total of 51
      grams of rscu-PA were produced in 1,000 liters of medium. The rscu-PA produced
      over the course of this continuous culture was purified and characterized both in
      vitro and in vivo and shown to be comparable to natural scu-PA produced from the
      transformed human kidney cell line, TCL-598.

PMID- 1367427
TI  - Biosynthesis of the tropane-related cyanobacterial toxin anatoxin-a: role of
      ornithine decarboxylase.
AB  - A study was made of the biosynthesis by Anabaena flos-aquae of the tropane
      related alkaloid anatoxin-a. Evidence is presented that the toxin arises from
      ornithine via putrescine (1,4-diaminobutane) and that ornithine decarboxylase (EC
      4.1.1.17) is involved. An ornithine decarboxylase preparation, with optimal
      activity at pH 8, was obtained from Anabaena flos-aquae and partially purified by
      gel-filtration chromatography on DEAE-cellulose. One major and one minor peak of
      enzymic activity were obtained with Km values of 1.25 and 2.5 mM, respectively.
      Plasmid DNA (10 Kb; Mr 6.5 x 10(6] was detected in the toxic strain of Anabaena
      flos-aquae but not in a non-toxic strain. DNA from the toxin-producing strain of
      Anabaena flos-aquae transforms the non-toxic into a toxic strain.

PMID- 1367429
TI  - Cyclodextrin-facilitated bioconversion of 17 beta-estradiol by a phenoloxidase
      from Mucuna pruriens cell cultures.
AB  - After complexation with beta-cyclodextrin, the phenolic steroid 17 beta-estradiol
      could be ortho-hydroxylated into a catechol, mainly 4-hydroxyestradiol, by a
      phenoloxidase from in vitro grown cells of Mucuna pruriens. By complexation with
      beta-cyclodextrin the solubility of the steroid increased from almost insoluble
      to 660 microM. The bioconversion efficiency after 72 hr increased in the
      following order: freely suspended cells (0%), immobilized cells (1%), cell
      homogenate (6%), phenoloxidase preparation (40%). Mushroom tyrosinase converted
      17 beta-estradiol, as a complex with beta-cyclodextrin, solely into 2
      hydroxyestradiol, with a maximal yield of 30% after 6-8 hr. Uncomplexed 17 beta
      estradiol was not converted at all in any of these systems.

PMID- 1367428
TI  - Production of desferrioxamine E and new analogues by directed fermentation and
      feeding fermentation.
AB  - Streptomyces olivaceus TU 2718 produces the siderophore desferrioxamine E.
      Production depends on L-lysine and iron concentrations in the medium. With
      optimized conditions the yield of desferrioxamine E could be increased to 12 g/l
      in feeding fermentations. Supplementation of the basic production medium with
      natural and synthetic precursors of desferrioxamine E led to the production of
      twelve new analogues of desferrioxamine E.

PMID- 1367430
TI  - Development of a FIA system with immobilized enzymes for specific post-column
      detection of purine bases and their nucleosides separated by HPLC column.
AB  - A sensitive and highly selective method for the simultaneous determination of
      purine bases and their nucleosides is proposed. An amperometric flow-injection
      system with the two immobilized enzyme reactors (guanase immobilized reactor and
      purine nucleoside phosphorylase/xanthine oxidase co-immobilized reactor) is used
      as the specific post-column detection system of HPLC, to convert compounds
      separated by a reversed-phase. HPLC column to electroactive species (hydrogen
      peroxide and uric acid) which can be detected at a flow-through platinum
      electrode. The proposed detection system is specific for a group of purine bases
      and purine nucleosides and does not respond for purine nucleotides and pyrimidine
      bases. The linear determination ranges are from 10 pmol to 5 nmol for four purine
      bases (hypoxanthine, xanthine, guanine, and adenine) and four purine nucleosides
      (inosine, xanthosine, guanosine, and adenosine). The detection limits are 1.2-5.5
      pmol.

PMID- 1367431
TI  - The effects of a biosurfactant on oxygen transfer in a cyclone column reactor.
AB  - A laboratory-scale cyclone column reactor was tested to determine how its oxygen
      transfer characteristics were affected by surfactants in the liquid medium. The
      volumetric oxygen transfer coefficient was greatly decreased by small quantities
      of the synthetic surfactants dodecyltrimethylammonium bromide and sodium
      dodecylsulfate, and the biosurfactant surfactin produced by Bacillus subtilis
      (ATCC 21332). Since the gas holdup fraction was generally increased due to
      foaming, the effectiveness of the surfactants was probably due to an increase in
      the interfacial film resistance. B. subtilis was grown in the cyclone column to
      0.6 g dm-3 with a significant level of surfactin produced while maintaining at
      least 75% oxygen saturation in the broth. Process optimization and scale-up of
      surfactin production will have to consider oxygen transfer as a key parameter.

PMID- 1367432
TI  - Measuring and increasing protein stability.
AB  - Recently, it has become possible to construct proteins to order and this has
      promoted interest in learning how to increase their stability. This article
      describes recent developments in the methods used to measure the conformational
      stability of globular proteins, and discusses the approaches being used to
      increase their stability.

PMID- 1367433
TI  - Alterations in the domain structure of tissue-type plasminogen activator change
      the nature of asparagine glycosylation.
AB  - The formation of N-linked oligosaccharides of eukaryotic glycoproteins starts
      with the attachment of a common precursor at the recognition site Asn-X-Ser/Thr.
      Subsequent processing, by yet unknown controlling factors, leads to the formation
      of three different glycans: the high mannose type, the complex type and the
      hybrid type. In order to gain insight into the processing mechanisms, we studied
      the glycan pattern of a panel of related molecules constructed by insertion,
      duplication or deletion of the domains encoded by the cDNA of a fibrinolytic
      glycoprotein, tissue-type plasminogen activator (t-PA). These variant molecules
      are identical in regard to the glycosylation sites originally situated in
      particular domains, but differ with respect to the sequential alignment of the
      domains. The variant and native t-PA genes were transfected into mouse C127 cells
      and their carbohydrate structures analyzed by the susceptibility to specific
      endoglycosidases and by reaction with sugar-specific lectins. We found that with
      one exception, all mutant activators lack the high mannose glycan found at asn
      117 of native t-PA. The exception was a molecule that retains the original domain
      arrangement up to and through the glycosylation site at asn 117. These results
      demonstrate for the first time that structural alterations in the primary
      sequence distal to the actual glycosylation site can result in altered processing
      of N-linked oligosacharides.

PMID- 1367434
TI  - Competition in the marketplace. t-PA trials, tribulations, and litigation.

PMID- 1367435
TI  - Wolffish antifreeze protein from transgenic Drosophila.
AB  - We have expressed two antifreeze protein genes from the Atlantic wolffish,
      Anarhichas lupus, in Drosophila melanogaster by placing them under the divergent
      transcriptional control of the host yolk polypeptide (1 and 2) gene promoters.
      Both genes were joined to the central promoter region by fusion within the DNA
      encoding the signal polypeptides. The chimeric genes were introduced into
      flightless mutant Drosophila through P-element transformation. Transformed adult
      females from individual lines accumulated 1.5-5 mg/ml of antifreeze protein in
      their hemolymph. The protein was purified to homogeneity from hemolymph following
      thermal denaturation, step elution from SP-Sephadex, and reverse-phase HPLC. It
      was recovered in high yield and retained full biological activity even though one
      of the two gene fusions gave rise to a seven amino acid N-terminal extension on
      its antifreeze protein product.

PMID- 1367436
TI  - Expression of recombinant proteins in Escherichia coli using an oxygen-responsive
      promoter.
AB  - The oxygen-dependent promoter of the Vitreoscilla hemoglobin (VHb) gene has been
      shown to be functional in E. coli. Earlier studies established that the promoter
      is maximally induced under microaerobic conditions and that its activity is also
      influenced by the cAMP-CAP complex. We demonstrate here that the promoter can be
      used for regulated, high-level expression of recombinant proteins in two-stage
      fed-batch fermentations. The promoter is maximally induced at dissolved oxygen
      levels lower than 5% air saturation. Despite the influence of catabolite
      repression, glucose and glycerol-containing media give comparable product levels
      under carbon-limited conditions such as those encountered in typical fed-batch
      fermentations. The possibility of a third level of control of promoter activity
      is also indicated. This mode of induction can be repressed by addition of a
      complex nitrogen source such as yeast extract to the medium. The observed
      promoter activity can be modulated at least 30-fold over the course of high-cell
      density fermentations producing either cloned beta-galactosidase or cloned
      chloramphenicol acetyltransferase (CAT). Densitometer scanning of SDS
      polyacrylamide gels revealed that beta-galactosidase was expressed to a level of
      approximately 10% of total cellular protein.

PMID- 1367437
TI  - Hypersecretion of a cellulase from Clostridium thermocellum in Bacillus subtilis
      by induction of chromosomal DNA amplification.
AB  - We have inserted a DNA fragment composed of (i) the promoter and the export
      signal of the Bacillus subtilis levansucrase gene; (ii) the sequence encoding the
      mature part of the Clostridium thermocellum endoglucanase A gene in a specific
      site of the B. subtilis chromosome. The insert was flanked by directly repeated
      pBR322 sequences of 3.9 kb. Plasmid pE194, which has a thermosensitive
      replication, was integrated adjacent to one of the repeats. When the integrated
      plasmid was allowed to replicate, the insert and one of the repeats was amplified
      up to a level of about 250 copies per chromosome. Endoglucanase A was efficiently
      synthesized in, and secreted from, cells containing the amplified structure,
      since the heterologous fusion protein was the major extracellular protein in a B.
      subtilis sacUh strain. The NH2-terminal sequence of the secreted protein revealed
      three different cleavage sites in the vicinity of the signal peptidase
      recognition sequence.

PMID- 1367438
TI  - Subtilisin-catalysed peptide synthesis and transesterification in organic
      solvents.
AB  - Subtilisin from Bacillus subtilis was modified with polyethylene glycol (PEG), or
      adsorbed either on celite or porous glass, or directly used as a suspended powder
      to catalyse peptide synthesis and transesterification reactions in organic
      solvents. The rather low yield of peptide synthesis probably resulted from the
      enzyme tendency to catalyse hydrolysis and transesterification side reactions.
      The kinetics of transesterification catalysed by PEG-subtilisin was consistent
      with a ping-pong mechanism modified by a hydrolytic branch. Initial rates of
      transesterification were found to be dependent on alcohol and organic base
      concentrations in the reaction mixture. The high affinity of benzyloxycarbonyl-L
      serine-methyl ester as compared to benzyloxycarbonyl-L-phenylalanine-methyl ester
      for the enzyme indicated that a change in substrate specificity of subtilisin
      occurred in organic phase. The 50-fold increase in the rate of synthesis of
      benzyloxycarbonyl-L-serine-L-phenylalanine amide which was observed when PEG
      subtilisin was used instead of immobilized or powdered enzyme, suggested that a
      higher flexibility of the polypeptide chain modified by the covalent attachment
      of a number of soluble PEG moieties occurred in organic solvents. This also
      resulted in a lower stability of PEG-subtilisin at high temperature.

PMID- 1367439
TI  - Synthesis of 9-(beta-D-arabinofuranosyl)guanine using whole cells of Escherichia
      coli.
AB  - Synthesis of 9-(beta-D-arabinofuranosyl)guanine (ara-G) from 1-(beta-D
      arabinofuranosyl)cytosine (ara-C) and guanine, guanosine or 2'-deoxyguanosine
      (dG) by glutaraldehyde-treated Escherichia coli BM-11 cells is described. It is
      shown that the concentration of phosphate ions, molar ratio of substrates and pH
      of the reaction medium are factors affecting product yield. Under optimum
      conditions ara-G was produced in the reaction mixture in a yield of 63%-65% based
      on dG as the best source of guanine base. The yield of isolated ara-G was 48%
      53%.

PMID- 1367440
TI  - Effect of medium composition on the maintenance of a recombinant plasmid in
      Bacillus subtilis.
AB  - Recombinant plasmid pCED3 [confers beta-galactosidase production (LacZ+) and
      kanamycin resistance (Kmr)] in Bacillus subtilis was found to be both
      segregationally and structurally unstable. Since many solutions to segregational
      instability are already available, the problem of structural instability was
      specifically addressed by inclusion of kanamycin in the growth media. Culture
      instability was found to be highest in complex and defined media supporting high
      growth rates. Stabilization over the duration of the experiment (40 generations)
      was achieved by use of a recently developed chemically defined medium supporting
      a lower growth rate. Slowing down growth by decreasing temperature was much less
      effective. A major effect of the growth medium appears to be that of decreasing
      the growth rate advantage held by cells with plasmid deletions over parental
      cells containing the intact plasmid.

PMID- 1367441
TI  - Immobilization and treatment of Streptococcus faecalis for the continuous
      conversion of arginine into citrulline.
AB  - Citrulline is one of the steps of the arginine dihydrolase system of
      Streptococcus faecalis. We have shown that the bacteria, immobilized in
      polyacrylamide gel and treated with Cetyl trimethyl ammonium bromide (CTAB) or
      heat, were able to convert arginine to citrulline. Used continuously in a column
      reactor, the entrapped cells have a stable enzymatic activity for at least 30
      days at 45 degrees C.

PMID- 1367442
TI  - Construction of a bioreactor for production of (R)-(-)-mandelate, a typical
      specialty chemical.

PMID- 1367443
TI  - Comparison of the performances of stirred tank and airlift tower loop reactors.
AB  - Following a consideration of the prerequisites for reactor comparison and the
      fundamental differences between stirred tank and airlift tower loop reactors,
      their performances are compared for the production of secondary metabolites:
      penicillin V by Penicillium chrysogenum, cephalosporin C by Cephalosporium
      acremonium, and tetracycline by Streptomyces aureofaciens. In stirred tank
      reactors, cell mass concentrations, volumetric productivities, and specific power
      inputs are higher than in airlift tower loop reactors. In the latter,
      efficiencies of oxygen transfer are higher, and specific productivities with
      regard to power input, substrate and oxygen consumptions, and yield coefficients
      of product formation with regard to substrate and oxygen consumptions are
      considerably higher than in stirred tank reactors. The prerequisites for improved
      performance are discussed.

PMID- 1367444
TI  - Recovery of biosurfactants by ultrafiltration.
AB  - Ultrafiltration was used in a one-step method to purify and concentrate
      biosurfactants--surfactin and rhamnolipids--from culture supernatant fluids. The
      ability of surfactant molecules to form micelles at concentrations above the
      critical micelle concentration allows these aggregates to be retained by
      relatively high molecular weight cut-off membranes. Lower molecular weight
      impurities such as salts, free amino acids, peptides and small proteins are
      easily removed. Various molecular weight cut-off membranes were examined for the
      retention of surfactin and rhamnolipids (mol. wts 1036 and 802 respectively).
      Amicon XM 50 was the superior membrane for retention of surfactin and a 160-fold
      purification was rapidly achieved. The YM 10 membrane was the most appropriate
      for rhamnolipid recovery. Ultrafiltration can play an important role in
      biosurfactant purification as large volumes of media can be processed rapidly at
      extremely low cost.

PMID- 1367445
TI  - The biosynthesis of proteases with fibrinolytic activity in immobilized cultures
      of Penicillium chrysogenum H9.
AB  - The yield of fibrinolytic and other proteolytic enzymes by Ca-alginate
      immobilized cells of Penicillium chrysogenum H9 was compared to that of free
      cells. The gel matrix protected the immobilized cells from lysis providing higher
      stability to the biocatalyst. The highest fibrinolytic activity/caseinase
      activity ratio was obtained in immobilized cell cultures. The composition of
      culture medium influenced enzyme production, showing different patterns in free
      and immobilized cultures. An alginate concentration of 3% and 10 ml alginate
      beads/50 ml medium were optimum for fibrinolytic enzyme biosynthesis.
      Semicontinuous production of the enzyme indicated the superiority of immobilized
      cells. The beads were affected by repeated exposure to phosphate ions after 12
      cycles.

PMID- 1367446
TI  - Effect of phosphate on antibiotic and extracellular protein production by
      Myxococcus coralloides D.
AB  - The effect of inorganic phosphate concentrations on antibiotic and extracellular
      protein production by Myxococcus coralloides D have been examined. Antibiotic
      production by growing cells of this myxobacterium was maximal at phosphate
      concentrations of 10-20 mM, but was inhibited by concentrations higher than 20
      mM. The total extracellular protein and the extracellular protein per cell ratio
      were independent of phosphate levels in the culture broth.

PMID- 1367447
TI  - Production of extracellular emulsifying agent by Pseudomonas aeruginosa UG1.
AB  - Twenty-three bacterial strains were isolated from oil-contaminated soil samples.
      Of these, 20 displayed some ability to effect oil dispersion and they were
      screened quantitatively for the ability to emulsify 0.5% (v/v) reference oil. One
      strain, identified as Pseudomonas aeruginosa UG1, produced extracellular material
      that emulsified reference oil, hexadecane and 2-methylnaphthalene at
      concentrations as high as 6% (v/v) in nutrient broth. Emulsification activity
      increased during a 10 day incubation period at 30 degrees C. The activity was not
      influenced by pH over the range 5 to 9. The emulsifying agent was precipitated by
      cold ethanol. The highest emulsifying activity was detected in the extracellular
      fraction precipitated between 30 and 50% (v/v) ethanol. A linear relationship was
      observed between emulsifier concentration (mg/ml) and emulsifying activity.
      Genetic analysis showed that the Pseudomonas aeruginosa UG1 strain did not carry
      extrachromosomal plasmids, suggesting that the gene(s) coding for emulsifying
      activity was carried on the chromosome.

PMID- 1367448
TI  - Purification, characterization, and amino terminal sequence of xylose reductase
      from Candida shehatae.
AB  - D-Xylose is a major component of the carbohydrates derived from agricultural
      residues and forest products. Among more than two hundred known xylose-utilizing
      yeasts, only a few species are known to be able to ferment xylose anaerobically.
      Candida shehatae is one of such xylose-fermenting yeasts. Xylose reductase (E.C.
      1.1.1.21) is a key enzyme responsible for xylose metabolism in xylose-utilizing
      as well as xylose-fermenting yeasts. In this paper, we report the development of
      a convenient and reliable procedure for the purification of xylose reductase from
      C. shehatae to near homogeneity. The amino acid composition and N-terminal
      sequence of the enzyme have also been analyzed. C. shehatae seems to contain only
      a single xylose reductase, but the enzyme has a dual coenzyme specificity for
      both NADPH and NADH. The enzyme is remarkably stable at room temperature and 4
      degrees C.

PMID- 1367449
TI  - Stability index for enzymes deactivating by different mechanisms.
AB  - A quantitative procedure for estimating changes in enzyme stability upon chemical
      modification is presented. Stability index for different deactivation mechanisms
      is presented and applied to different enzyme deactivations. The stability index
      provides a convenient method of estimating changes in enzyme stability upon
      chemical modification.

PMID- 1367450
TI  - Aflatoxin monoclonals: academic development to commercial production.
AB  - A monoclonal antibody (mAb) has been produced to aflatoxin B1 (AF B1) after
      successful immunization of mice and fusion of sensitized spleen cells with
      myeloma cancer cells. The mice were immunized with AF B1-oxime-protein conjugate.
      Positive mAbs were screened using an indirect ELISA specific for AF B1. The
      selected mAb was then developed in direct competitive ELISA and immunoaffinity
      column chromatography methods for aflatoxin detection in foods and feeds. Both
      assays are rapid, sensitive, specific and require only the minimum of sample
      preparation. Both immunological assays have now been commercialized and are
      produced in convenient ready-made kit formats.

PMID- 1367451
TI  - Structural and functional repetition in a marine mussel adhesive protein.
AB  - The DOPA-rich polyphenolic protein secreted by the marine mussel Mytilus edulis
      establishes key chemical linkages in a water-resistant adhesive. Molecular
      cloning of the gene for this remarkable protein reveals its primary structure as
      one of the most repetitive proteins identified in the animal kingdom. Expression
      and purification of polyphenolic proteins from recombinant yeast have provided
      sufficient material to demonstrate adhesivity of these polypeptides in the
      laboratory. Adhesive tests reveal a water-resistant bonding capacity of the
      protein that is dependent on in vitro modification of tyrosine residues to DOPA
      and the subsequent oxidation to quinone.

PMID- 1367452
TI  - Experimental and theoretical evidence for convective nutrient transport in an
      immobilized cell support.
AB  - Even though immobilized-cell reactors possess several engineering advantages over
      free-cell reactors, their full potential has not been realized because mass
      transfer often limits the rate of nutrient supply and product removal from
      immobilized cell supports. We studied the interaction between mass transfer and
      reaction kinetics in the anaerobic conversion of glucose to CO2 and ethanol by
      yeast immobilized in a porous rotating disk on the agitator shaft of a
      conventional CSTR. A Sherwood number correlation was used to show that external
      mass-transfer resistances were negligible under typical operating conditions. The
      modulus of Weisz based on observable reaction parameters was used to gauge the
      importance of pore diffusion limitations. Under conditions for which significant
      pore diffusion effects and hence low effectiveness factors (eta = ca. 0.1) would
      be predicted, the observed reaction rates were much higher than expected (eta =
      ca. 1), suggesting that pore diffusion limitations were at least partially
      relieved by convective transport of glucose into the support. Two possible
      mechanisms of convective transport are discussed. We hypothesize that gas
      evolution was responsible for the convective enhancement of glucose supply.

PMID- 1367453
TI  - Production of monoclonal antibodies to Pseudomonas syringae pv. phaseolicola and
      Xanthomonas campestris pv. phaseoli.
AB  - The production of monoclonal antibodies (MAbs) to ethylenediamine tetraacetic
      acid (sodium salt) soluble antigens of Pseudomonas syringae pv. phaseolicola and
      Xanthomonas campestris pv. phaseoli (fuscans strain) is described. MAbs A6-1 and
      A6-2 produced to Ps. syringae pv. phaseolicola are pathovar specific. Although
      MAb XP2 produced to X. campestris pv. phaseoli recognized surface antigens of all
      strains of this pathovar (including fuscans strains) it cross-reacted
      specifically with X. campestris pv. malvacearum; it did not react with any other
      known bacteria or unidentified epiphytes from navy bean seed or leaves. The
      isotype of both MAbs XP2 and A6-1 is IgG3 whereas that of MAb A6-2 is IgG2a. The
      reactive antigens are thermostable, but their chemical nature has not been
      determined.

PMID- 1367454
TI  - A molecular biological approach to reducing dietary amino acid needs.
AB  - Rapid developments in transgenic animal technology make it possible to consider
      introducing new metabolic capabilities into animals, using genes from other
      species. Lysine and threonine are both essential amino acids in mammals, and are
      commonly the first and second limiting amino acids, respectively, for protein
      accretion in pigs and poultry fed cereal based diets. Here we consider the
      potential for transgenic animals with microbial biosynthetic pathways for these
      amino acids.

PMID- 1367455
TI  - Melanin production in Escherichia coli from a cloned tyrosinase gene.
AB  - We have cloned and functionally expressed a tyrosinase gene from Streptomyces
      antibioticus in Escherichia coli under the control of an inducible bacteriophage
      T7 promoter. Recombinant E. coli cells containing the induced tyrosinase gene
      produced melanin pigments on agar plates and in liquid culture when supplemented
      with copper and tyrosine. The expression of an additional open reading frame from
      the mel gene locus of S. antibioticus was required for high-level melanin
      production in E. coli. Our results also show that it is possible to screen other
      classes of precursor compounds for incorporation into melanin pigments with
      unique colors and other biochemical features. In addition, it may be possible to
      screen for enhanced melanin production in the absence of added precursors to
      identify overproducing mutants in the amino acid biosynthetic pathways of E.
      coli. The ability to screen for a melanin phenotype in recombinant E. coli
      provides new opportunities for production of novel melanins and for protein
      engineering of tyrosinases with altered catalytic properties.

PMID- 1367456
TI  - Antibody production in baculovirus-infected insect cells.
AB  - We have employed the baculovirus expression system for the production of a mouse
      monoclonal IgG antibody directed against lipoprotein I of Pseudomonas aeruginosa.
      Both light and heavy chain cDNAs were introduced into the baculovirus genome in a
      single step of homologous recombination. Insect cells that were infected with the
      recombinant virus stably secreted antigen-binding and glycosylated antibody
      molecules capable of binding the complement component C1q.

PMID- 1367457
TI  - Anchorage-dependent mammalian cell culture using polyurethane foam as a new
      substratum for cell attachment.
AB  - Anchorage-dependent mammalian cells were cultivated at high cell density in a
      novel culture system using polyurethane foam (PUF) as a substratum for cell
      attachment. PUF has a macroporous structure giving a high surface area to volume
      ratio. Monkey kidney cells (Vero) and Chinese hamster ovary cells (CHO-K1)
      attached to the internal surface of PUF and grew to a high cell density (1.04 X
      10(8) cells/cm3 PUF and 3.5 X 10(7) cells/cm3 PUF, respectively) in PUF
      stationary cultures. In addition, we have designed a PUF-particle packed-bed
      culture system for high density mass cell culture. A maximum cell density of 2.4
      X 10(7) cells/cm3 culture vessel volume was obtained in a packed-bed culture of
      Vero cells.

PMID- 1367458
TI  - From LIF to ESGRO.

PMID- 1367459
TI  - Characteristics of arachidonic acid metabolism of human endothelial cells in
      culture.
AB  - Human umbilical endothelial cells in culture retain differentiated morphological
      and functional characterization in primary culture and even in the early
      subcultures, after which they begin to degenerate. We have studied the
      morphological and biochemical characterization (ability to produce prostacyclin,
      prostaglandin E2 and thromboxane A2 in culture) of endothelial cells in the first
      seven subcultures. In addition the influence of serum and endothelial cell growth
      factor added to the culture medium have been evaluated. With 20% normal human
      serum, cell proliferation is faster than with the same concentration of human
      fetal or bovine fetal serum. After the 3rd passage, morphological and growth
      alterations become observable in the endothelial cells. However, prostacyclin,
      prostaglandin E2 and thromboxane A2 production showed no variations during the
      study.

PMID- 1367460
TI  - Heterohybridomas that secrete high levels of pseudomonas-specific therapeutic
      human monoclonal antibodies: their generation and large scale growth in an
      automated hollow fiber cell culture system.
AB  - Fusion of lymphoblastoid cell lines that produce human monoclonal antibodies
      against Pseudomonas aeruginosa with the human/mouse heteromyeloma SHM-D33
      generated heterohybrids that were stable and secreted antibody in the range of 20
      to 300 micrograms/ml. One of the hybridoma cell lines ws adapted to serum-free
      medium and maintained for 60 days in an automated hollow fiber system. During
      that time, 3 g of antibody was produced. Such yields make it possible to evaluate
      these monoclonals for their therapeutic potential in patients at risk for
      Pseudomonas infections.

PMID- 1367462
TI  - Microbial sensor.

PMID- 1367461
TI  - Comparative behaviour of L-929 fibroblastic and human endothelial cells onto
      crosslinked protein substrates.
AB  - Studies were carried out to compare the behaviour of human umbilical vein
      endothelial cells (HUVEC) and L-929 fibroblastic cells towards proteins
      crosslinked by glutaraldehyde (GTA) or carbodiimide (CDI) proposed for coating of
      vascular prostheses. CDI crosslinking of bovine serum albumin used alone, or
      mixed with gelatin, allowed higher rates of cell growth and DNA synthesis than
      GTA crosslinking independent of cells. Assessment of the plating efficiency
      revealed a similar behaviour of both cells towards membranes and reference
      plastic surface in terms of percentages of bound cells. HUVEC proliferation onto
      CDI crosslinked gelatin and/or albumin membranes did not differ significantly
      whereas the growth of L-929 was enhanced onto gelatin albumin membranes in
      comparison with both gelatin membranes and the reference surface. The analysis of
      DNA synthesis corroborated the results of the growth curves and elicited a delay
      of the growth phases in HUVEC cultured onto CDI crosslinked membranes, unlike the
      L-929 fibroblast.

PMID- 1367463
TI  - Isolation and characterization of acetonitrile utilizing bacteria.
AB  - Bacteria utilizing high concentrations of acetonitrile as the sole carbon source
      were isolated and identified as Chromobacterium sp. and Pseudomonas aeruginosa.
      Maximum growth was attained after 96 h of incubation and P. aeruginosa grew
      slightly faster than Chromobacterium sp. The strains were able to grow and
      oxidize acetonitrile at concentrations as high as 600 mM. However, higher
      concentrations inhibited growth and oxygen uptake. Degradation studies with
      (14C)acetonitrile indicated 57% of acetonitrile was degraded by Pseudomonas
      aeruginosa as compared to 43% by Chromobacterium. The isolates utilized different
      nitrile compounds as carbon substrates.

PMID- 1367464
TI  - The production of recombinant beta-galactosidase in Escherichia coli in yeast
      extract enriched medium.
AB  - The productivity of Escherichia coli biomass and recombinant beta-galactosidase
      was increased in Luria broth (LB) enriched with yeast extract. In flask culture
      under conditions of LB limitation, yeast extract supplementation gave the highest
      biomass (strain HB101/pRW756) stimulation per unit of component added compared
      with supplementation by various amounts of amino acids, vitamins, minerals,
      purines/pyrimidines, tryptone, casamino acids, casein peptone or gelatin peptone.
      The biomass production of E. coli HB101/pRW756, XL-1 Blue/puc118, XL-1 Blue
      FF/puc118 and TB-1/p1034 cells was stimulated in fermentor-scale experiments with
      additional yeast extract in LB. Total beta-galactosidase production from plasmid
      genes in fermentor-scale experiments was increased 105.4% in XL-1 blue/puc118
      cells, 365.5% in XL-1 blue FF/puc118 cells and 421.4% in TB-1/p1034 cells by
      0.5%, 1% and 1% weight per volume of additional yeast extract in LB,
      respectively. Depending on different strains, the increase of the enzyme
      production was obtained either by increased biomass, or the combination of
      enhanced gene expression and increased biomass. Neither the biomass nor beta
      galactosidase production was stimulated in N4830/p1034 cells by the increase in
      yeast extract concentration in the medium.

PMID- 1367465
TI  - DNA distribution and respiratory activity of Spodoptera frugiperda populations
      infected with wild-type and recombinant Autographa californica nuclear
      polyhedrosis virus.
AB  - Spodoptera frugiperda cells were infected with a wild-type Autographa californica
      nuclear polyhedrosis virus and with a recombinant Autographa californica nuclear
      polyhedrosis virus. The recombinant virus was derived from the wild-type virus
      and produced beta-galactosidase instead of polyhedrin. The changes in cell size,
      cell growth, viability, DNA distribution, and respiratory activity were followed
      through the time course of the infection. The DNA content as measured by flow
      cytometry of infected cells increased to approximately 1.8 times the value of
      uninfected cells and the distributions of single-cell DNA content of the infected
      cells were strongly deformed. Early in the infection the respiratory activity
      passed through a maximum. The mitochondrial activity based on Rhodamine 123
      labelling of cells infected with the recombinant virus, as determined by flow
      cytometry, also passed through a maximum at 24 h post infection while the
      mitochondrial activity of cells infected with the wild-type virus continued to
      increase. Evolution of single-cell mitochondrial activity was different in
      uninfected populations and in populations infected with wild-type and with
      recombinant virus. In all experiments performed, the recombinant virus influenced
      cell behavior and the measured parameters earlier than the wild-type virus. The
      influence of the multiplicity of infection was stronger for the wild-type virus
      than for the recombinant virus.

PMID- 1367467
TI  - Detection of Listeria species and Listeria monocytogenes using polymerase chain
      reaction.
AB  - Five oligonucleotide sequences are described that were used as primers in the
      polymerase chain reaction (PCR) to amplify specific sequences from Listeria DNA.
      When all five primers were used in combination, three PCR products were possible;
      a Listeria specific product that occurs with DNA from any Listeria sp., a
      Listeria monocytogenes specific product that occurs only in the presence of DNA
      from this organism and a universal product that is found using DNA from any
      bacterial source. The occurrence of these PCR products was used as a diagnostic
      test on bacteria isolated from various food samples to detect Listeria sp. and L.
      monocytogenes.

PMID- 1367466
TI  - Waste treatment technologies from the Genesearch Group of companies.
AB  - Genesearch is a 10 year old research and development company of Australian
      scientists, specializing in microbiology and genetics. This research expertise
      has formed the basis of a number of microbial processes for waste treatment. In
      addition, a novel type of high yield fermenter for aerobic bacteria allows the
      economical production of high-potency bacterial preparations for waste treatment
      processes. A novel approach to the rapid biodegradation of polychlorinated
      biphenyls has been developed. Photochemical pretreatment partially dechlorinates
      the molecules, rendering them susceptible to complete and rapid digestion by wild
      type soil bacteria. In the area of non-toxic waste, Genesearch has developed
      products for on-site treatment of, for example, grease-trap wastes and waste oil
      in ship bilges; and a large scale process for conversion of municipal grease
      wastes into protein-rich biomass. The prospects for novel biological waste
      treatment are improving, as public pressure grows, and as increasing government
      monitoring and penalties make inadequate waste disposal uneconomic.

PMID- 1367468
TI  - High efficiency electroporation of Lactococcus lactis subsp. lactis LM0230 with
      plasmid pGB301.
AB  - Electroporation-mediated transformation of Lactococcus lactis with plasmid
      pGB301, a 9.8 kilobase pair vector (Behnke et al. 1981), has been reported by
      McIntyre & Harlander (1989a). Improved transformation efficiencies of 10(2)
      10(3)/micrograms DNA were achieved by altering the conditions under which the
      bacteria were grown prior to electroporation (McIntyre & Harlander 1989b). This
      present investigation sought to improve still further transformation efficiencies
      in order to provide a reliable high frequency transformation system for Lc.
      lactis subsp. lactis.

PMID- 1367469
TI  - The D-galactose dehydrogenase gene from Pseudomonas fluorescens: characterization
      of mutations leading to increased expression in Escherichia coli.
AB  - The gene encoding D-galactose dehydrogenase (gld; E.C. 1.1.1.48) from Pseudomonas
      fluorescens is poorly expressed when cloned into Escherichia coli. Mutagenesis of
      the wild-type construct leads to a strong expression of gld in the heterologous
      host. To investigate the mutational events directing the increase in expression
      we constructed a gld-lacZ translational fusion which facilitated the isolation of
      mutants by colony screening. From several independent mutants three point
      mutations could be identified. They were distinguished by the sequence position
      of their respective single base-pair substitutions in the 5'-untranslated region
      of the gld gene and the degree of enhancement of enzyme activity of the gene
      product. The influence of these mutations on gld gene expression was analysed by
      S1 protection analysis which revealed that their effect was at the level of
      transcription.

PMID- 1367471
TI  - Effect of organic substrates on biological sulphide oxidation.
AB  - Neither acetate nor higher fatty acids and glucose have a significant effect on
      the biotechnological process for sulphide removal at 20 degrees C, in which
      sulphide is oxidized to sulphur using oxygen. The oxidation of acetate and
      propionate with oxygen is mainly dependent on the sulphide and oxygen
      concentrations in the reactor. The occurrence of Thiothrix filaments in sulphide
      removing waste-water treatment systems has been investigated using a fixer-film
      upflow reactor. The influent of this reactor consisted of anaerobically treated
      paper-mill waste-water, with a sulphide concentration of 140 mg/l. It was found
      that sulphide loading rate is the decisive parameter as to whether or not
      Thiothrix will develop in a sulphide-removing reactor.

PMID- 1367470
TI  - Production and characterization of human gamma interferon from Escherichia coli.
AB  - The production of human gamma interferon as intracellular inclusion bodies in
      Escherichia coli, which simplified the purification process, is described. An
      expression plasmid carrying lipoprotein and the tryptophane promoters in tandem
      was used. Preparation of highly pure interferon was achieved using high
      resolution chromatography after denaturation and renaturation steps. Structural
      characteristics of this protein were verified by mass spectrometric analysis.
      Additional control tests have shown the suitability of the final product for
      clinical purposes.

PMID- 1367472
TI  - Towards understanding human genetic diseases.

PMID- 1367473
TI  - Use of early baculovirus promoters for continuous expression and efficient
      processing of foreign gene products in stably transformed lepidopteran cells.
AB  - Baculoviruses are currently used as vectors for the transient high-level
      expression of foreign gene products in insect cells. In this study, we
      demonstrate that baculoviruses can also be made to continuously express a foreign
      gene product by using the promoter from IE1, an immediate early viral gene, to
      produce stably-transformed insect cells. This approach gave levels of foreign
      gene expression lower than those usually obtained with the lytic baculovirus
      expression vector system. Expression, however, was continuous and stable, and a
      complex human glycoprotein (tissue plasminogen activator) was processed more
      efficiently. We conclude that stable transformation is a feasible approach for
      baculovirus-mediated foreign gene expression in lepidopteran cells, particularly
      for products that are relatively poorly-expressed and/or processed in lytically
      infected cells.

PMID- 1367474
TI  - A novel screening system for yeast strains capable of secreting tissue
      plasminogen activator.
AB  - We have developed a simple screening procedure that allowed us to identify
      Saccharomyces cerevisiae strains able to secrete human tissue plasminogen
      activator (tPA) into the culture medium. The screen can be used to isolate more
      efficient secretor strains and to look for novel tPA analogs. Employing one of
      these strains to study the effect of glycosylation on secretion, we show that
      glycosylation in the catalytic domain of tPA plays an important role in folding
      and/or secretion of the molecule. Removing this glycosylation site resulted in a
      3-5-fold reduction in the level of tPA secretion. We anticipate that this system
      will prove useful in studying yeast secretory pathway as well as structure
      function relationships in the tPA molecule.

PMID- 1367475
TI  - Selective flocculation with chitosan in Escherichia coli disintegrates: effects
      of pH and nuclease treatment.
AB  - The flocculation of cell debris from a beta-galactosidase constitutive E. coli
      with chitosan as a flocculant was studied to investigate the possibility of
      obtaining a selective flocculation in cell disintegrates with high product
      recoveries. The flocculation removed 98% of the cell debris by 30 min
      sedimentation under gravity, which should be compared to a separation of the cell
      debris without flocculation of only 70% by centrifugation at 15,000 g. Optimal
      flocculation dosages varied between 12 and 43 mg chitosan g-1 dry weight of
      cells, depending on pH. The yield of the product beta-galactosidase reached 60%
      at optimal pH. Hydrolysis of the nucleic acids by DNAase and RNAase decreased the
      optimal flocculation dosages considerably. The study showed that the flocculation
      is somewhat selective, since chitosan also removed 85% of the nucleic acids and
      50% of the proteins, which contributed to the purification of the protein
      solution.

PMID- 1367477
TI  - Synthesis and biological activity of some 5-substituted aminomethyl-8
      hydroxyquinoline-7-sulphonic acids.
AB  - 5-Aryl (or alkyl)-8-hydroxyquinoline-7-sulphonic acids have been prepared by the
      Mannich reaction of 8-hydroxyquinoline-7-sulphonic acid with primary and
      secondary amines. Their bactericidal activities have been determined.

PMID- 1367476
TI  - A bifunctional vector system for controlled expression and subsequent release of
      the cloned gene product by phi X174 lysis protein-E.
AB  - A new bifunctional Escherichia coli cloning vector, pSB50, is presented. The
      plasmid allows controlled expression of a gene of interest under control of the
      lac promoter and the subsequent release of the cloned product by the use of
      bacteriophage phi X174 lysis protein-E, the gene of which is under control of the
      phage Lambda pL promoter. To ensure optimal repression of the Lambda pL promoter
      and the lac promoter in plasmid pSB50, E. coli strain UB89-1 was constructed
      which carries a chromosomal copy of the lambda cl857 repressor allele and the
      laclq1 allele, respectively. Here, we employ the E-based lysis system to release
      human prourokinase to the culture medium.

PMID- 1367478
TI  - Amperometric bi-enzyme based biosensor for the detection of lactose-
      characterization and application.
AB  - Based on the glucose oxidase-beta-galactosidase sequence an enzyme probe for the
      specific determination of lactose has been developed. beta-Galactosidases from
      different sources have been compared, the sensor containing beta-galactosidase
      from Curvularia inaequalis has been characterized in respect of optimal pH,
      enzyme loading, apparent activity and functional stability. The response of the
      bi-enzyme probe depends linearly on lactose concentration between 0.02 and 3.00
      mmol dm-3. The application to different milk and foodstuff samples resulted in
      good correlations toward enzymatic photometric (y = (0.956x-1.67) mmol dm-3) and
      infrared detection (y = (1.0772x-0.3909)%). Using a measuring frequency of 100 h
      1 the serial imprecision is about 2% for diluted milk, urine, or foodstuff
      samples.

PMID- 1367479
TI  - Evaluation of intrinsic immobilized kinetics in hollow fiber reactor systems.
AB  - Immobilized cell and enzyme hollow fiber reactors have been developed for a
      variety of biochemical and biomedical applications. Reported mathematical models
      for predicting substrate conversion in these reactors have been limited in
      accuracy because of the use of free-solution kinetic parameters. This paper
      describes a method for determining the intrinsic kinetics of enzymes immobilized
      in hollow fiber reactor systems using a mathematical model for diffusion and
      reaction in porous media and an optimization procedure to fit intrinsic kinetic
      parameters to experimental data. Two enzymes, a thermophilic beta-galactosidase
      that exhibits product inhibition and L-lysine alpha-oxidase, were used in the
      analysis. The intrinsic kinetic parameters show that immobilization enhanced the
      activity of the beta-galactosidase while decreasing the activity of L-lysine
      alpha-oxidase. Both immobilized enzymes had higher Km values than did the soluble
      enzyme, indicating less affinity for the substrate. These results are used to
      illustrate the significant improvement in the ability to predict substrate
      conversion in hollow fiber reactors.

PMID- 1367480
TI  - Use of a rapid bioluminescence assay for detecting cyanobacterial microcystin
      toxicity.
AB  - The recent rise in the awareness of the occurrence of toxic cyanobacterial blooms
      in aquatic environments, with associated human health problems and animal deaths,
      has increased the need for rapid, reliable and sensitive methods of determining
      cyanobacterial toxicity. A luminescent bacterial toxicity test was assessed as a
      complement to the established mouse bioassay. Seventeen samples including pure
      cyanobacterial microcystin-LR hepatotoxin, laboratory isolates and natural blooms
      of cyanobacteria were tested and toxicity data compared with mouse LD50 values.
      Microcystin-LR and all five microcystin-containing cyanobacterial samples,
      hepatotoxic by mouse test gave EC50 values of less than 0.46 mg/ml in
      bioluminescence-based Microtox assays. Of 11 samples non-toxic by mouse bioassay,
      only two gave an EC50 of less than 0.98 mg/ml by bioluminescence assay. It is
      suggested that the Microtox bioluminescence assay may prove useful in the
      preliminary screening of cyanobacterial blooms for microcystin-based toxicity.

PMID- 1367481
TI  - Penicillin production by glucose-derepressed mutants of Penicillium chrysogenum.
AB  - Wild-type strains of Penicillium chrysogenum produce lower penicillin V titers in
      media containing excess glucose. Two mutant strains were isolated and shown to
      produce normal penicillin V titers in the presence of excess glucose. These
      strains, designated as glucose-repression insensitive (GRI) mutants, produced
      higher penicillin V titers than the wild-type strain in media containing lactose
      as the main carbohydrate source. In lactose-based media, the production of
      penicillin V was depressed to a much lesser extent by in-cycle additions of
      glucose with the GRI mutants when compared to the wild-type strain. In short-term
      biosynthesis experiments using washed cells in a medium containing glucose as the
      sole carbon source, the GRI mutants produced penicillin V at a faster rate than
      the wild-type strain. In fed-batch fermentations in 14-liter fermentors, where
      glucose was fed continuously and pH controlled, both GRI mutants produced more
      than 10% higher penicillin V titers than the wild-type strain. These results
      suggest that isolation of GRI mutants is an effective way to select for higher
      producing strains and that the synthesis of penicillin synthesizing enzymes in
      GRI mutants may be less repressed by glucose than in wild-type strains.

PMID- 1367482
TI  - Improvement of glidobactin A production by Polyangium brachysporum.
AB  - Glidobactins A, B, and C are lipopeptide antitumor antibiotics produced by the
      gliding bacterium Polyangium brachysporum sp. nov. No. K481-B101. The production
      of glidobactin A was examined in shake flasks and laboratory fermentors. Medium
      screening and optimization led to approximately five fold increases in
      glidobactin A titers in shake flasks and a ten fold increase in titers in 40-l
      batch fermentations. Utilization of a stepped glucose feeding protocol resulted
      in glidobactin A titers of 1860 micrograms/ml after 144 h of fermentation.

PMID- 1367483
TI  - Polyelectrolyte precipitation of beta-galactosidase fusions containing poly
      aspartic acid tails.
AB  - Protein recovery from industrial microbial processes can be very expensive, often
      exceeding the cost of protein production. We have genetically engineered 3 beta
      galactosidase (beta-gal) fusion proteins containing poly-aspartic acid tails to
      test the effect of the tails on recovery by the relatively inexpensive method of
      polyelectrolyte precipitation. The fusion proteins, designated T1, T2, and T3,
      were constructed with C-terminal tails of 5, 11, and 16 aspartic acid residues,
      respectively. The fusion proteins were expressed in Escherichia coli, and
      purified by affinity chromatography. T1 and T2 had specific activities similar to
      that of wildtype beta-gal, whereas the specific activity of T3 was about half
      that of T1 and T2. The increased net charge of the fusion proteins compared to
      wildtype beta-gal was indicated both by ion-exchange chromatography and their
      migration pattern in non-denaturing polyacrylamide gel electrophoresis. All three
      tails enhanced polyethyleneimine (PEI) precipitation of the fusion proteins
      compared to wildtype beta-gal. At a low PEI/protein ratio (0.01, g g-1), recovery
      by precipitation of T2 and T3 was more than 2 X that of the beta-gal control,
      whereas that of T1 was only slightly greater than that of the control. At a
      higher PEI/protein ratio (0.03, g g-1) the amount of precipitation of all three
      fusion proteins was nearly the same, about 1.5 X that of the control.

PMID- 1367484
TI  - A method for the stabilisation of recombinant plasmids in yeast.
AB  - The stability of a yeast plasmid can be improved using deliberately induced
      cyclic changes in the dissolved oxygen tension (DOT), during continuous culture
      in a non-selective, undefined medium. The resultant stability of the plasmid
      under DOT cycled conditions is strongly dependent on the growth rate of the
      culture, with complete stabilisation at lower growth rates. We propose a
      mechanism for the stabilisation and suggest that the method can be applied to
      other recombinant yeast strains.

PMID- 1367485
TI  - Regulation of biosynthesis of bacilysin by Bacillus subtilis.
AB  - Production of the dipeptide antibiotic bacilysin by Bacillus subtilis 168 was
      growth associated and showed no evidence of repression by glucose or sucrose.
      Carbohydrates other than glucose and sucrose yielded lower specific titers of
      bacilysin. Bacilysin production in three such carbon sources (maltose, xylose,
      ribose) was delayed until growth slowed down. Ammonium salts were poor for
      bacilysin production when used as the sole nitrogen source. When added to the
      standard medium containing glutamate, they suppressed antibiotic production.
      Aspartate was slightly better than glutamate for antibiotic production as sole
      nitrogen source. No other nitrogen source tested, including inorganic, organic or
      complex, approached the activity of glutamate or aspartate. When added to
      glutamate, casamino acids, phenylalanine and alanine (a substrate of bacilysin
      synthetase) suppressed bacilysin production while stimulating growth. Phosphate
      provided for optimum growth and production at 7.5 mM and both processes were
      inhibited at higher concentrations. Ferric citrate stimulated growth and
      inhibited bacilysin production, the effects being due to both the iron and the
      citrate components. Elimination of ferric citrate stimulated production as did
      increasing the concentration of Mn to its optimum concentration of 6.6 x 10(-4)
      M.

PMID- 1367486
TI  - In vitro expression of Lac-PTS and tagatose 1,6-bisphosphate aldolase genes from
      Lactococcus lactis subsp. cremoris plasmid pDI-21.
AB  - A 4.4-kb EcoR1-EcoR1 DNA fragment from the Lactococcus lactis subsp. cremoris
      plasmid pDI-21 encoded the tagatose 1,6-bisphosphate (TBP) aldolase gene and the
      Lac-PTS genes. In vitro transcription-translation using Escherichia coli S30
      extract showed the synthesis of 41,000-, 23,000- and 12,000-dalton proteins which
      correspond to the TBP-aldolase, Lac-PTS enzyme II, and factor III proteins
      respectively.

PMID- 1367487
TI  - The role of monic acid A in pseudomonic acid A biosynthesis in Pseudomonas
      fluorescens.
AB  - The putative role of monic acid A as a biosynthetic intermediate of the
      antibiotic pseudomonic acid A, providing a C17 moiety requiring only
      esterification with a C9 fatty acid, has been tested by administration of
      [14C]monic acid A early in the pseudomonic acid A idiophase of a Pseudomonas
      fluorescens fermentation. [14C]Monic acid A was not taken up by the cells and the
      pseudomonic acid A subsequently accumulated was not radiolabelled. Experimental
      demonstration of the biosynthetic role of monic acid A and the potential use of
      monate analogues in biotransformations will require unexpectedly elaborate
      strategies to ensure the uptake of these compounds into bacterial protoplasts.
      The impermeability to monic acid A explains for the first time why it is not an
      antibiotic.

PMID- 1367488
TI  - Cosolvent assisted protein refolding.
AB  - The use of cosolvents in aqueous systems has been shown to enhance protein
      refolding and decrease aggregation. In this study, we have used polyethylene
      glycol (PEG) in the molecular weight range of 1000 to 8000 Daltons to effectively
      increase the rate of refolding and prevent aggregation of the model protein,
      bovine carbonic anhydrase B (CAB). At concentrations of 3 and 30 g/l, PEG
      increased the rate of recovery of active protein in the absence of aggregation.
      Using 3 g/l PEG (3350 MW), the refolding rate was three fold greater than the
      observed normal refolding rate. The observed rate enhancement was caused by PEG
      acting on the first intermediate in the CAB refolding pathway to increase the
      rate of formation of the second intermediate. The interaction of PEG with the
      first intermediate also prevented its self-association during refolding and at
      equilibrium. The stabilization of this first intermediate resulted in complete
      recovery of active protein under normal aggregating conditions.

PMID- 1367489
TI  - Expression of three recombinant proteins using baculovirus vectors in 23 insect
      cell lines.
AB  - Recombinant Autographa california baculoviruses expressing genes for pseudorabies
      virus glycoprotein (gp50T), human plasminogen (HPg), and beta-galactosidase (beta
      gal) were used to infect 23 cell lines or strains. The objectives were to compare
      amounts of recombinant proteins expressed in the cell lines, compare yields from
      clones and parent lines, investigate the effects of long-term culture in serum
      free medium on production, and determine if some lines yield gp50T with different
      glycosylation patterns. For HPg, IZD-MB0503 had the highest yield and four other
      lines (IPLB-TN-R2, IPLB-SF-1254, IPLB-LdEIta, and CM-1) had levels above that of
      SF-9 cells. For gp50T, four lines (IPLB-HvT1, IPLB-SF21AE, IPLB-SF21AE-15, and
      IPLB-SF-1254) had higher amounts than SF-9 cells. Some lines yielded gp50T with
      molecular mass about 1000 daltons larger than that from SF-9 cells, which
      suggests increased oligosaccharide processing. Equally high levels of beta-gal
      were expressed in three lines (SF-9, IZD-MB0503, and BCIRL-PX2-HNV3). The major
      conclusion is that no single cell line produced highest yields for all three
      recombinant proteins. Four lines were cultured in serum-free medium for 31-34
      passages and then infected with the three recombinant viruses. For most cell line
      recombinant combinations, the yields in serum-free medium were equal to or better
      than those in serum-supplemented medium. Medium composition had a much stronger
      effect on foreign gene expression than on susceptibility of cells to wild-type
      virus.

PMID- 1367490
TI  - Production of 5-methyluridine by immobilized thermostable purine nucleoside
      phosphorylase and pyrimidine nucleoside phosphorylase from Bacillus
      stearothermophilus JTS 859.
AB  - 5-Methyluridine was produced continuously from thymine and inosine by immobilized
      enzymes, which consisted of thermostable purine nucleoside phosphorylase and
      thermostable pyrimidine nucleoside phosphorylase obtained from Bacillus
      stearothermophilus JTS 859. The process was carried out in a column reactor at 60
      degrees C for 17 d without any bacterial contamination under non-aseptical
      conditions. Half-lives of the activity of the immobilized enzymes were 47 d and
      4.5 d at 60 degrees C and 70 degrees C, respectively, although half-life of the
      crude enzyme was only 14 h at 70 degrees C.

PMID- 1367491
TI  - Expression of penicillin G acylase gene from Bacillus megaterium ATCC 14945 in
      Escherichia coli and Bacillus subtilis.
AB  - Penicillin G acylase gene from Bacillus megaterium ATCC 14945 has been isolated.
      Recombinant Escherichia coli clones were screened for clear halo forming activity
      on the lawn of Staphylococcus aureus ATCC 6538P using the enzymatic acylating
      reaction of 7-aminodeacetoxycephalosporanic acid (7-ADCA) and D-(alpha)
      phenylglycine methylester. The gene was contained within a 2.8 kb DNA fragment
      and expressed efficiently when transferred from E. coli to Bacillus subtilis. A
      twenty times greater amount of enzyme was produced in B. subtilis transformant
      than that in B. megaterium. The purified enzyme from subcloned B. subtilis showed
      that the native enzyme consisted of two identical subunits, each with a molecular
      weight of 57,000. The enzyme was able to react on various cephalosporins, i.e.,
      cephalothin, cefamandole, cephaloridine, cephaloglycin, cephalexin and
      cephradine.

PMID- 1367492
TI  - Enzyme-linked immunosorbent assays for detection of Pseudomonas fluorescens in
      sediment samples.
AB  - A strain-specific antibody to Pseudomonas fluorescens was used to develop two
      enzyme-linked immunosorbent assays: a sandwich and a competitive assay. Both
      assay types could be used to perform rapid and sensitive detection of the target
      organism in extracts of sediment samples.

PMID- 1367493
TI  - A 6 h microslide immunodiffusion assay for confirmed detection of staphylococcal
      enterotoxins.
AB  - Use of appropriately balanced immunological reagents and incubation of
      microslides at 45 degrees C resulted in confirmed assay results in 6 h for
      staphylococcal enterotoxins. The sensitivity of the 45 degrees C-6 h assay was
      comparable to the 37 degrees C-24 h assay: 0.1 micrograms of staphylococcal
      enterotoxin A/ml.

PMID- 1367494
TI  - Intracellular and extracellular production of proteins in Aspergillus under the
      control of expression signals of the highly expressed Aspergillus nidulans gpdA
      gene.
AB  - The expression in Aspergillus is described of genes, coding for intracellular and
      extracellular proteins controlled by the promoter region of the constitutively
      and efficiently expressed glyceraldehyde-3-phosphate dehydrogenase gene (gpdA) of
      Aspergillus nidulans. Both the homologous gpdA and the heterologous Escherichia
      coli beta-galactosidase (lacZ) and beta-glucuronidase (uidA) genes could be
      expressed intracellularly at levels as high as 10-25% of total soluble protein.
      Efficient extracellular production of A. niger glucoamylase could be achieved
      with a fusion-gene containing the region of the glucoamylase gene coding for the
      mature protein preceded by a synthetic fungal signal sequence. Extracellular
      production of a heterologous protein, E. coli beta-glucuronidase, with such a
      fusion was much less efficient. Only very low levels of beta-glucuronidase were
      detected in the culture fluid, whereas considerable enzyme activity was detected
      in the mycelium.

PMID- 1367495
TI  - Molecular characterization and functional analysis in Aspergillus nidulans of the
      5'-region of the Penicillium chrysogenum isopenicillin N synthetase gene.
AB  - The isopenicillin N synthetase gene (pcbC) was isolated from a genomic library of
      Penicillium chrysogenum BC39813, a penicillin production strain. The nucleotide
      sequence, including 555 bp upstream of the translation start site was determined.
      Various deletions within the pcbC 5'-region were constructed and linked to the
      Escherichia coli lacZ gene. An Aspergillus nidulans argB strain was transformed
      with DNA of these constructions. The region essential for promoter function could
      be localized between positions -307 and -89 by analyzing beta-galactosidase
      expression of transformants containing a single copy of the corresponding plasmid
      integrated at the homologous argB locus. A region responsible for regulatory
      effects concerning nitrogen metabolism was identified by determining beta
      galactosidase activities in cell-lysates of transformants cultivated under
      varying growth conditions. Two major transcription start sites at positions -131
      and -132, as well as a further upstream located site at position -397 +/- 1 could
      be located by primer extension studies employing RNA isolated from P. chrysogenum
      BC39813.

PMID- 1367496
TI  - Strain improvement of Penicillium chrysogenum by recombinant DNA techniques.
AB  - The penDE gene from Penicillium chrysogenum has been isolated; the gene is
      located in close vicinity of the pcbC gene. Amplification of the pcbC-penDE gene
      cluster in Penicillium chrysogenum Wis54-1255 leads to a significant increase in
      penicillin production. In selected transformants an increase of up to 40% is
      observed.

PMID- 1367497
TI  - Design of two immobilized cell catalysts by entrapment on gelatin: internal
      diffusion aspects.
AB  - Experimental results obtained during the design of two immobilized cell catalysts
      by entrapment on gelatin are presented. Strong diffusional limitations are found
      and explained with the usual parameters and models, introducing an empirical
      correlation between substrate concentration and effectiveness factor. The effect
      of particle size, enzyme load, and specific activity in the system is discussed
      in terms of cooperation between bioengineers and geneticists.

PMID- 1367498
TI  - Partitioning of beta-galactosidase fusion proteins in PEG/potassium phosphate
      aqueous two-phase systems.
AB  - Four different beta-galactosidase fusion proteins have been partitioned in
      poly(ethylene glycol) (PEG) 4000/potassium phosphate aqueous two-phase systems.
      The partition coefficients (K) of staphylococcal protein A-beta-galactosidase
      (SpA beta gal) (K = 3.5) and staphylococcal protein A-streptococcal protein G
      beta-galactosidase (AG beta gal) (K = 2.8) were compared with the partition
      coefficients of their constituent molecules, beta-galactosidase, SpA, and protein
      AG. It was found that by fusing beta-galactosidase to the smaller proteins SpA
      and protein AG, their partition coefficients were increased four to five times.
      Experimental data were fitted into, and found to agree with, the Albertsson
      partition model of interacting molecules. The compatibility with PEG and
      potassium phosphate of beta-galactosidase, SpA, and two different versions of the
      SpA beta gal protein, displayed as precipitation curves, showed a relationship to
      the protein partition coefficients in PEG/potassium phosphate systems. High
      solubility in one phase component was accompanied by preferential partitioning to
      the phase rich in the same component in the PEG/potassium phosphate system. Also,
      a changed linker region in SpA beta gal resulted in a more soluble protein. This,
      together with the improved K values of the target proteins by fusion, shows that
      it is possible to use beta-galactosidase as an affinity handle.

PMID- 1367499
TI  - Feedback regulation and the intracellular protein profile of Streptomyces griseus
      in a cycloheximide fermentation.
AB  - Two-dimensional gel electrophoresis (2-D PAGE) was used to study the
      intracellular protein profile of Streptomyces griseus in relation to
      cycloheximide (CH) biosynthesis. Four proteins (CR1-CR4) were found to be
      significantly and specifically repressed by addition of the antibiotic (1 g/l at
      72 h) to a producing fermentation. Synthesis of these proteins was specific to
      the idiophase, concurrent with CH production. Initial addition of CH to the
      production medium resulted in slightly lower synthesis rates of two of the
      proteins (CR1 and CR2), while significantly delaying the onset of synthesis of
      the other two (CR3 and CR4). Finally, neutral polymeric resin was added to the
      fermentation to alleviate feedback regulation of CH synthesis, giving roughly a
      twofold increase in the antibiotic production rate. Production of proteins CR3
      and CR4 was increased approximately tenfold immediately following resin addition,
      but returned to the control rate of synthesis after 24 h.

PMID- 1367500
TI  - Production of recombinant human erythropoietin in Bowes melanoma cells in
      suspension culture.
AB  - Recombinant DNA technology was used to insert a fetal liver genomic library ApaI
      fragment encoding for human erythropoietin (Epo) into Bowes melanoma cells. The
      cells expressed the erythropoietin gene, and Epo was secreted into the culture
      medium together with the normally-secreted tissue plasminogen activator. Attempts
      to grow the cells in glass spinners in Dulbecco's medium supplemented with fetal
      bovine serum produced cell aggregates growing in suspension. When calcium-free
      suspension culture media (Joklik, DME-S, McCoy 5A-S) were used, single cell
      suspension cultures were obtained and high Epo production observed. When attempts
      were made to scale up the small glass spinners, poor growth or Epo production
      occurred unless the vessels were aerated. This was shown to be because of the
      drop in pH, possibly due to CO2 accumulation, rather than due to oxygen
      depletion. It was shown that a semi-continuous operation could be achieved in
      aerated 8-1 spinners fitted with either a conventional stirrer or a vibromixer
      agitator. The system was scaled up to a 100-1 stainless steel vessel fitted with
      a vibromixer agitator. This system was operated for over 4 months with weekly
      harvests producing over 100 million units of Epo in about 1000-1 of culture
      fluid. Interference by the serum proteins with downstream purification of the
      hormone from the culture fluid made the use of serum-free media highly desirable.
      Studies showed that the Epo was produced in serum-free systems containing
      peptones.

PMID- 1367501
TI  - Quality control of rDNA-derived human tissue-type plasminogen activator.

PMID- 1367502
TI  - Purification and production of therapeutic grade proteins.

PMID- 1367503
TI  - Proteases during purification.

PMID- 1367504
TI  - Redesigning t-PA for improved thrombolytic therapy.
AB  - Attempts are being made to redesign the structure of tissue-type plasminogen
      activator (t-PA) in order to increase its plasma half-life, increase its fibrin
      affinity or decrease its rate of interaction with plasma inhibitors. The
      principal strategies employed so far have been to construct hybrid enzymes, to
      mutate the polypeptide sequence of t-PA or to add extra fibrin-binding elements.
      It has been relatively easy to alter the half-life of t-PA but more difficult to
      do this with retention of the full specific activity of the molecule; the most
      promising molecules will have to be evaluated in the clinic before we know
      whether the redesign of t-PA has been truly successful.

PMID- 1367505
TI  - Stability of a host-vector system based on complementation of an essential gene
      in Escherichia coli.
AB  - Antibiotic selection is the most common selection system for plasmid-containing
      bacteria. This technique, nevertheless, can be a source of problems during the
      expression of heterologous genes in Escherichia coli. We have developed an
      alternative selection system based on the complementation of a chromosomal
      auxotrophic (dapD2) mutation by the corresponding wild type gene carried on a
      plasmid. We show that the system effectively selects for the presence of plasmid
      on solid and liquid medium. In addition, we have observed a loss of viability
      associated with high levels of gene expression and accumulation of a heterologous
      protein, but the selective power and improved intrinsic stability of the dap+
      plasmid, compared to a beta-lactamase (bla) based vector, excludes overgrowth of
      the culture by plasmidless cells.

PMID- 1367506
TI  - A new human growth hormone production process using a recombinant Bacillus
      subtilis strain.
AB  - We constructed a series of hybrid plasmids which directed the synthesis of
      different human growth hormone (hGH) precursor sequences in Bacillus subtilis. In
      addition to the 191 amino acids of the hormone, the precursors had in common an
      amino-terminal extension characterized by the presence of a methionine at
      position 1 and of the tetrapeptide Ile-Glu-Gly-Arg preceding the first residue
      (Phe) of hGH. The sequence between the methionine and the tetrapeptide was
      specific for each precursor and, because of the presence of charged residues,
      conferred particular properties to the molecules. Long homopolymeric tail
      containing precursors such as MRRRRRRIILM-IEGR appeared insoluble whereas shorter
      sequences of the type MRR-IEGR and MEELM-IEGR augmented the solubility of the
      precursors with respect to Met-hGH. The soluble precursors could be easily
      purified from the bulk proteins taking advantage of the charged residues present
      on the N-terminal tail. After purification, the natural hGH was obtained by
      treating the precursors with the protease Factor Xa which cleaves after the
      arginine residue of the tetrapeptide IEGR. A protocol for the production and
      purification of authentic hGH from a strain expressing one of these soluble
      precursors is reported.

PMID- 1367507
TI  - Temperature and induction effects on the degradation rate of an abnormal beta
      galactosidase in Escherichia coli.
AB  - Intracellular protein degradation was investigated using an unstable fragment of
      Escherichia coli beta-galactosidase, the CSH11 mutant, as a model protein. This
      abnormal protein was expressed from a single copy gene in the chromosome and is
      converted to a detectable degradable intermediate. The in vivo degradation rates
      of both beta-galactosidase fragments were measured using pulse-chase radioactive
      labeling techniques, and their intracellular concentrations were determined using
      alpha-complementation assays. In the physiological range of 30 to 37 degrees C,
      the apparent degradation rate constant for the CSH11 fragment follows Arrhenius
      behavior; while the intermediate's apparent degradation rate constant is nearly
      unchanged. However, above 37 degrees C the degradation rates of both fragments
      increase significantly. Analysis of the labeled intermediate's rate of change
      above 40 degrees C reveals that the CSH11 fragment is being degraded by a second
      pathway which does not produce the intermediate. When the induction level of the
      abnormal beta-galactosidase was varied the degradation rates of both fragments
      behaved similarly, but they unexpectedly decreased with increasing IPTG
      concentration. The two parallel degradation pathways for CSH11 apparently
      operated at only the lower IPTG levels. The measured degradation rates did not
      correlate directly with the intracellular concentration of abnormal proteins.

PMID- 1367508
TI  - Decreased production of para-hydroxypenicillin V in penicillin V fermentations.
AB  - Penicillin V (phenoxymethyl penicillin) is produced by industrial strains of
      Penicillium chrysogenum in the presence of phenoxyacetic acid (POAc), a side
      chain precursor for the penicillin V molecule. The wild-type strain of P.
      chrysogenum produces an undesirable penicillin byproduct, para-hydroxypenicillin
      V (p-OH penicillin V), in addition to penicillin V, via para-hydroxylation of
      POAc and subsequent incorporation of the p-OH phenoxyacetic acid into the
      penicillin molecule. Most of the p-OH penicillin V is produced late in cycle when
      the POAc concentration in the medium is nearly depleted. The level of p-OH
      penicillin V produced by the control strain ranges up to 10-15% of the total
      penicillins produced. 3-Phenoxypropionic acid and p-bromophenylacetic acid
      partially inhibit the formation of p-OH penicillin V with a minimal effect on
      penicillin V productivity. Mutants deficient in their ability to hydroxylate POAc
      were found to produce lower levels of p-OH penicillin V. Multi-step mutation and
      screening, starting with the wild-type strain, have culminated in isolation of
      mutants which produce p-OH penicillin V as 1% of the total penicillins with no
      adverse effect on penicillin V productivity.

PMID- 1367509
TI  - Beijerinckia indica var. penicillanicum penicillin V acylase: enhanced enzyme
      production by catabolite repression-resistant mutant and effect of solvents on
      enzyme activity.
AB  - Beijerinckia indica var. penicillanicum mutant UREMS-5, producing 168% more
      penicillin V acylase, was obtained by successive treatment with UV, gamma
      irradiation and ethylmethane sulfonate. Penicillin V acylase production by the
      mutant strain was resistant to catabolite repression by glucose. Incorporation of
      glucose, sodium glutamate and vegetable oils in the medium enhanced enzyme
      production. The maximum specific production of penicillin V acylase was 244 IU/g
      dry weight of cells. Effect of solvents on hydrolysis of penicillin V by soluble
      penicillin V acylase and whole cells was studied. Methylene chloride, chloroform
      and carbon tetrachloride significantly stimulated the rate of penicillin V
      hydrolysis by whole cells.

PMID- 1367510
TI  - Genetically modified organisms in commercial use.

PMID- 1367511
TI  - Transport and kinetics in sandwiched membrane bioreactors.
AB  - A bioreactor in which living yeast cells are sandwiched between an
      ultrafiltration membrane and a reverse osmosis membrane was constructed, and
      experiments were performed for the conversion of substrate glucose to product
      ethanol. A set of equations that include both transport through a series of
      barrier layers and bioreaction rate were developed to predict the performance of
      the sandwich bioreactor. The above equations were solved by using numerical
      values for the transport parameter and the bioreaction rate constant, and the
      results are compared with the experimental data.

PMID- 1367512
TI  - Antibody immobilization onto glow discharge treated polymers.
AB  - Previous studies have shown that certain glow discharge treated polymers strongly
      retain adsorbed albumin and fibrinogen. On the basis of this phenomenon, we have
      investigated the possibility of immobilizing antibodies on glow discharge treated
      surfaces for diagnostic immunoassay applications. As a model for antibody
      immobilization, bovine IgG was immobilized on the following polymers:
      polyethylene (PE), tetrafluoroethylene glow discharge treated PE (TFE/PE),
      poly(ethylene terephthalate) (PET), TFE/PET, poly(tetrafluoroethylene) (PTFE),
      ethylene glow discharge treated PET (E/PET) and hexamethyldisiloxane glow
      discharge treated PET (HMDS/PET). IgG was radiolabeled with 125I and immobilized
      by either of the following two methods: (a) physical adsorption of IgG on
      untreated and glow discharge treated polymers or (b) physical adsorption of
      albumin followed by chemical coupling of IgG to albumin by glutaraldehyde. IgG
      concentration as well as adsorption times were varied in order both to optimize
      the immobilization conditions and to investigate the adsorption and retention
      mechanisms. To evaluate the efficiency of the immobilization techniques, blood
      plasma, Tween-20, and sodium dodecyl sulfate (SDS) were used to elute the
      adsorbed IgG layer. We found that IgG was successfully immobilized on the
      fluorocarbon glow discharge treated surfaces by using either the physical
      adsorption or the glutaraldehyde coupling method, although the former is more
      efficient than the latter method.

PMID- 1367513
TI  - Immobilization of Escherichia coli JM103[pUC8] in kappa-carrageenan coupled with
      recombinant protein release by in situ cell membrane permeabilization.
AB  - Immobilization of Escherichia coli JM103[pUC8] was carried out with kappa
      carrageenan as the support matrix. Substantial natural excretion of beta
      lactamase, attributable to the less intact membrane of plasmid-harboring cells,
      was observed in immobilized cell cultures. Nevertheless, a significant portion of
      the beta-lactamase produced was retained in the cells. As compared to suspension
      cultures, much higher beta-lactamase activities, especially in the extracellular
      liquid, and much longer retention of plasmid-bearing cells (improved plasmid
      stability) were observed in immobilized cell cultures. Further enhancement in
      excretion of the recombinant protein (beta-lactamase) was achieved by
      permeabilization of cell membrane by periodic exposure of the immobilized cell
      cultures to ethylenediaminetetraacetic acid (EDTA). While the presence of EDTA
      led to some suppression of cell growth in suspension cultures, cell growth in gel
      beads was not affected by EDTA to the same extent, possibly due to lesser
      exposure of immobilized cells to EDTA. Exposure of immobilized cell cultures to
      EDTA presumably inhibited plasmid replication and led in turn to diversion of
      cellular resources for the support of expression of plasmid genes. Indeed,
      treatment of the immobilized cell cultures with EDTA resulted in increased
      production of beta-lactamase when compared to the enzyme production in EDTA-free
      cultures. More frequent addition of EDTA increased the period of retention of
      plasmid-bearing cells in these cultures but did not have any noticeable adverse
      effect on synthesis of beta-lactamase. Improvement in plasmid stability in EDTA
      treated immobilized cell cultures was ascribed to the reduction in the growth
      rate differential between plasmid-free and plasmid-bearing cells, since plasmid
      free cells were subject to more reduction in specific growth rate than were
      plasmid-bearing cells.

PMID- 1367514
TI  - Alginate biosynthesis in mucoid recombinants of Pseudomonas aeruginosa
      overproducing GDP-mannose dehydrogenase.
AB  - The Pseudomonas aeruginosa algD gene, encoding GDP-mannose dehydrogenase (GMD)
      and cloned at Chakrabarty's Laboratory in the expression vector pMMB24 (plasmid
      pVD211), was mobilized into P.aeruginosa strains 8821 and 8821M. Strain 8821M was
      a high-alginate-producing variant, spontaneously obtained from mucoid strain
      8821, with derepressed levels of GMD, a key enzyme in the regulation of alginate
      biosynthesis, leading to the irreversible oxidation of GDP-mannose to GDP
      mannuronic acid. A slight increase in the level of GMD, in both strains harboring
      the plasmid pVD211 and batch-grown at 37 degrees C without IPTG induction, led to
      the increase of production rate and the final concentration of alginate produced
      by control strains harboring the cloning vector. However, the viscosity of the
      aqueous solutions prepared with the alginate (3 g l-1) produced by mucoid strains
      harboring pVD211 was lower than those with the alginate produced by the controls
      (shear rates in the range 0.6-12 s-1). The specific activity of GMD assayed in
      crude extracts from cells harboring pVD211 and subjected to IPTG induction (0.5
      and 3 mM) presented the highest values. However, either the rate of biosynthesis
      and final concentration of alginate or the viscosity of solutions prepared with
      the alginate produced by recombinants grown with IPTG were lower than that
      possible without overproduction. Therefore, the stimulation of the alginate
      pathway only by manipulating the rate of the step catalysed by GMD, although
      possible within certain levels, was at the expense of the final exopolysaccharide
      quality.

PMID- 1367515
TI  - Extractive purification of enzymes from animal tissue using aqueous two phase
      systems: pilot scale studies.
AB  - Pilot scale trials have been carried out to assess the feasibility of using PEG
      salt aqueous phase systems for extraction and purification of enzymes from animal
      tissue on an industrial scale. Comminuted bovine liver was used as a starting
      material, and it was easy to separate a clear upper phase containing proteins of
      interest from a mixture containing 20% biomass, 15% PEG and 8% phosphate using a
      disc separator. Similar attempts with decanters were unsuccessful. Second-phase
      separation was simply accomplished by the addition of salt to the separated,
      clear upper layer and standing or allowing passage through a disc separator. The
      method was tested using continuous mixing on the GBF continuous mixing aqueous
      phase extraction plant, with and without computer control. Good separations were
      achieved. The enzyme superoxide dismutase was purified using this method yielding
      a 4-fold purification factor with respect to soluble protein and a recovery rate
      of 83%, with the enzyme in a clarified solution suitable for further processing
      by chromatographic methods. The general applicability of this method, its
      economics and its potential application in industry are discussed.

PMID- 1367516
TI  - Saccharomyces cerevisiae strains that overexpress heterologous proteins.
AB  - We describe a system that facilitates the selection of host mutants that
      overproduce a range of secreted and internally produced heterologous proteins in
      Saccharomyces cerevisiae. These mutants were initially selected for their ability
      to oversecrete recombinant human albumin (rHA), as detected by a direct visual
      assay that relies upon antibody precipitation in solid media. Yeast strains that
      were able to synthesize and secrete increased levels of rHA also produced
      elevated levels of internally expressed proteins including alpha 1-antitrypsin
      Pittsburgh variant and plasminogen activator inhibitor type 2.

PMID- 1367517
TI  - Mass spectrometry of peptides, proteins and glycoproteins.

PMID- 1367518
TI  - Ambruticin S production in air-lift and stirred-tank bioreactors.
AB  - Using the method of equi-inocular synchronized comparative fermentation (EISCF)
      the cultivation of Sorangium cellulosum So ce 10 and production of the polyketide
      antibiotic ambruticin S was compared in stirred-tank and air-lift reactors of
      different geometry. This method requires that inocula originate from the same pre
      culture and cultivation parameters are synchronized to similar values. Similar
      ambruticin yields were obtained from both reactor systems provided that the
      concentration of dissolved oxygen (DO) was maintained above a certain value (ca.
      40%). For cultivation of S. cellulosum it is the DO level rather than the oxygen
      transfer rate which presents the proper criterion for scale-up and comparative
      reactor studies.

PMID- 1367519
TI  - The genetic stability of Penicillium chrysogenum transformants in a fermentor.
AB  - A number of transformants of Penicillium chrysogenum have been obtained with the
      plasmid vector p3SR2. Southern analysis showed that transformation had occurred
      by integration of vector sequences into the nuclear DNA of the fungus. A number
      of transformants were tested for stability of the transformed phenotype in agar
      medium and some were found to be unstable. Two transformants, shown to be stable
      in agar culture, were grown in 5-1 batch fermentors for further stability tests.
      Over periods of up to 312 h in the fermentor both transformants were 100% stable
      with respect to the transformed phenotype. In addition Southern analysis of DNA
      extracted from the spent mycelium showed that no change had occurred in the
      position of the integrated vector sequences within the transformant nuclear DNA.

PMID- 1367520
TI  - Reversion of L-lysine inhibition of penicillin G biosynthesis by 6-oxopiperidine
      2-carboxylic acid in Penicillium chrysogenum PQ-96.
AB  - 6-Oxopiperidine-2-carboxylic acid (OCA; cyclic alpha-aminoadipic acid) reverses
      the L-lysine inhibition of penicillin G production by Penicillium chrysogenum PQ
      96. The reaction probably depends on the recovery of L-alpha-aminoadipic acid for
      penicillin G production from OCA.

PMID- 1367521
TI  - A hyperthermostable pullulanase produced by an extreme thermophile, Bacillus
      flavocaldarius KP 1228, and evidence for the proline theory of increasing protein
      thermostability.
AB  - A cell-associated pullulanase (alpha-dextrin 6-glucanohydrolase, EC 3.2.1.41) of
      an extreme thermophile, Bacillus flavocaldarius KP 1228, was purified to
      homogeneity. The molecular weight and isoelectric point were estimated to be
      about 55,000 and 7.0, respectively. The N-terminal sequence was Ala-Try-Tyr-Glu
      Gly-Ala-Phe-Phe-Tyr-Gln-Ile-Phe-Pro-Asp-Tyr-Phe-Phe-Tyr- Ala- Gly-. The enzyme
      was most active at pH 6.3. The activities for 5% pullulan and 5% soluble starch
      were maximal at 75-80 degrees C and at 80-85 degrees C, respectively. The enzyme
      was stable up to 90 degrees C for 10 min at pH 6.8. The enzyme had no antigenic
      determinants shared with pullulanases from the mesophiles Klebsiella pneumoniae
      and B. acidopullulyticus NCIB 11647. A comparison of amino acid composition
      demonstrated that the proline content increased greatly in a linear fashion with
      the rise in thermostability in the order K. pneumoniae----B. acidopullulyticus---
      B. flavocaldarius enzymes, as found with Bacillus oligo-1,6-glucosidases.

PMID- 1367522
TI  - Cloning and amplification of the gene encoding an extracellular beta-glucosidase
      from Trichoderma reesei: evidence for improved rates of saccharification of
      cellulosic substrates.
AB  - We have cloned and determined the nucleotide sequence of the gene encoding an
      extracellular beta-glucosidase (bgl1) from the cellulolytic fungus Trichoderma
      reesei. The predicted open reading frame of the bgl1 gene is interrupted by two
      putative introns of 70 and 64 bp and encodes a protein with a calculated
      molecular weight of 75,341. The genomic segment encoding bgl1 was cloned into a
      vector that contained the selectable marker gene, amdS. Transformation of T.
      reesei with this vector resulted in several stable transformant strains all
      possessing an increased copy number of the bgl1 gene integrated into the genome
      together with elevated rates of glucose production from avicel. One transformant
      produced an extracellular cellulase with a five-fold increase in the rate of
      production of glucose from cellobiose, a 33% rate increase from avicel, and a 17%
      increase from phosphoric acid swollen cellulose. These data suggest that the
      cellulolytic activity of T. reesei strains may be specifically improved by
      transformation with cloned cellulase genes.

PMID- 1367523
TI  - Optimizing the promoter and ribosome binding sequence for expression of human
      single chain urokinase-like plasminogen activator in Escherichia coli and
      stabilization of the product by avoiding heat shock response.
AB  - The expression of recombinant single-chain urokinase-like plasminogen activator
      (rscuPA) in Escherichia coli was optimized by fusing the puk gene to different
      promoters and ribosome binding sequences. Comparison of the tac, trp and lambda
      PL promoters showed that expression was maximal under tac control. Variation in
      the ribosome binding sequence and its distance to the AUG start codon yielded a
      further slight improvement of expression. The largest increase in rscuPA
      expression was achieved by variations in the host strain and growth conditions.
      In E. coli DG75 grown at 37 degrees C maximal expression was achieved 30 min
      after induction and decreased gradually until 240 min after induction. Growth at
      30 degrees C yielded maximal expression 60 min after induction and resulted in
      reduced activity at longer times. Western blot analysis of the products showed
      that degradation of rscuPA was much larger at 37 degrees C than at 30 degrees C.
      Using E. coli CAG630 carrying the htpR mutation, which avoids heat shock
      response, for expression of rscuPA eliminated the instability of the product at
      both temperatures. Expression in this strain was even more efficient than in E.
      coli JM101 carrying the lon mutation. It is concluded that induction of the
      general heat-shock response in E. coli must be avoided to obtain stabilization of
      rscuPA. This drastically improves the overall yield of rscuPA from recombinant E.
      coli strains.

PMID- 1367524
TI  - Chinese hamster ovary cell growth and interferon production kinetics in stirred
      batch culture.
AB  - Recombinant human interferon-gamma production by Chinese hamster ovary cells was
      restricted to the growth phase of batch cultures in serum-free medium. The
      specific interferon production rate was highest during the initial period of
      exponential growth but declined subsequently in parallel with specific growth
      rate. This decline in specific growth rate and interferon productivity was
      associated with a decline in specific metabolic activity as determined by the
      rate of glucose uptake and the rates of lactate and ammonia production. The
      ammonia and lactate concentrations that had accumulated by the end of the batch
      culture were not inhibitory to growth. Glucose was exhausted by the end of the
      growth phase but increased glucose concentrations did not improve the cell yield
      or interferon production kinetics. Analysis of amino acid metabolism showed that
      glutamine and asparagine were exhausted by the end of the growth phase, but
      supplementation of these amino acids did not improve either cell or product
      yields. When glutamine was omitted from the growth medium there was no cell
      proliferation but interferon production occurred, suggesting that recombinant
      protein production can be uncoupled from cell proliferation.

PMID- 1367525
TI  - Application of the tryptophanase promoter to high expression of the tryptophan
      synthase gene in Escherichia coli.
AB  - The application of an inducible regulation system using the tryptophanase operon
      promoter (TPase promoter; Ptna) was examined for its high expression of the
      tryptophan synthase (TS) gene in Escherichia coli. The main problem in the
      application of Ptna for industrial purposes is catabolite repression by glucose,
      since glucose is the most abundant carbon source. However, this problem could be
      avoided by changing glucose to an organic acid, such as succinate, fumarate,
      malate and acetate, in the course of cultivation after glucose initially added
      was completely consumed. Under these conditions, L-tryptophan was also used to
      induce tryptophan synthase. Thus, the specific activity of TS in E. coli strain
      no. 168 harbouring pBR322F-Ptna TS was increased 500-fold compared to that of the
      cultured host strain. About 1 mol L-tryptophan/l reaction mixture was formed from
      indole and L-serine at 37 degrees C for 3.5 h.

PMID- 1367526
TI  - Heterologous gene expression in continuous cultures of budding yeast.
AB  - In a previous paper we have studied the expression of beta-galactosidase from
      Escherichia coli, driven from the inducible GAL1-10/CYC1 hybrid promoter, in
      batch cultures of budding Saccharomyces cerevisiae and have described operating
      conditions for maximal productivity. In this paper we show that the plasmid
      instability in continuous cultures can be overcome by utilizing appropriate
      selection markers and a high copy number vector. The maximal level of expression
      is influenced by the dilution rate. Moreover, enzyme accumulation appears to
      depend also upon the degree of oxygenation. A possible explanation of these
      modulations is discussed, taking into account the interactions of the UAS-GAL and
      TATA-CYC1 elements.

PMID- 1367527
TI  - "Differentiation induction" culture of human leukemic myeloid cells stimulates
      high production of macrophage differentiation inducing factor.
AB  - A suitable procedure for the production of human monokines was defined as
      'differentiation-induction' culture. Human monocytic leukemia THP-1 cells were
      well-differentiated from nonfunctional promonocytes into macrophage-like cells by
      the induction with a combination of mezerein, retinoic acid, and a Mycoplasma
      fermentans extract. The differentiated THP-1 cells secreted a high amount of
      macrophage differentiation-inducing factor (DIF) activity and concomitantly
      produced other known monokines, such as tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta), into the
      medium. These results suggest that other novel human monokines may also be found
      in the conditioned medium of THP-1 cells induced by the 'differentiation
      induction' culture conditions defined in this study. Macrophage DIF was purified
      to homogeneity and NH2-terminal amino acid sequence analysis revealed that
      macrophage DIF is very similar or identical to human leukemia inhibitory factor
      (LIF). The cDNA encoding human LIF was isolated using the polymerase chain
      reaction, and a clone producing 3.7 micrograms/10(6) cells day recombinant LIF
      was selected from Chinese hamster ovary (CHO) cells which were transfected with
      the LIF cDNA. The recombinant LIF production in CHO cells was quantified using
      MTT reduction assay with M1 cells.

PMID- 1367528
TI  - Enzyme immobilization using a cellulose-binding domain: properties of a beta
      glucosidase fusion protein.
AB  - Using molecular genetic techniques, a fusion protein has been produced which
      contains the cellulose-binding domain (CBD) of an exoglucanase (Cex) from
      Cellulomonas fimi fused to a beta-glucosidase (Abg) from Agrobacterium sp. The
      CBD functions as an affinity tag for the simultaneous purification and
      immobilization of the enzyme on cellulose. Binding to cellulose was stable for
      prolonged periods at temperatures from 4 degrees C to at least 50 degrees C, at
      ionic strengths from 10 mM to greater than 1 M, and at pH values below 8. The
      fusion protein can be desorbed from cellulose with distilled water or at pH
      greater than 8. Immobilized enzyme columns of the fusion protein bound to cotton
      fibers exhibited stable beta-glucosidase activity for at least 10 days of
      continuous operation at temperatures up to 37 degrees C. At higher temperatures,
      the bound enzyme lost activity. The thermal stability of the fusion protein was
      greatly improved by immobilization. Immobilization did not alter the pH
      stability. Except for its ability to bind to cellulose, the properties of the
      fusion protein were virtually the same as those of the native enzyme.

PMID- 1367529
TI  - Elucidation and optimization of the medium constituents controlling antibiotic
      production by the cyanobacterium Nostoc muscorum.
AB  - A study has been made to determine which nutrient factors control antibiotic
      production by the cyanobacterium, Nostoc muscorum. A two-phase approach was
      employed using a factorial method to explore the response surface and a steepest
      ascent method to climb the response surface to the region of the optimum. It was
      found that nitrate and iron were the factors significantly affecting antibiotic
      production; 26.4 mM nitrate and 6 microM iron were the optimal concentrations for
      maximizing antibiotic production by N. muscorum.

PMID- 1367530
TI  - Production processes of recombinant IL-1 beta from Bacillus subtilis: comparison
      between intracellular and exocellular expression.
AB  - The human IL-1 beta coding sequence derived from a cDNA library was inserted into
      two different plasmid expression vectors, pSM214 and pSM308, which promote the
      synthesis of recombinant products intracellularly and exocellularly,
      respectively. The hybrid constructs pSM261 and pSM320 were obtained. Bacillus
      subtilis SMS118 was transformed with these plasmids and the recombinant strains
      were grown in 1 litre bioreactors. Different growth conditions were analyzed to
      optimize yields both in terms of biomass and IL-1 beta production. In the pSM261
      harbouring strain, IL-1 beta was synthesized in the cytoplasm to levels ranging
      from 1 to 2.7 mg g-1 of cells, corresponding to up to 40 mg l-1 of the culture.
      In contrast, SMS118(pSM320) was able to secrete 0.27 mg of natural IL-1 beta per
      g of cells (6.7 mg l-1 of culture). Processes for the purification of IL-1 beta
      from the supernatant and the biomass of the two cultures were also developed and
      compared in terms of yield and simplicity of the purification schemes. From our
      data it turns out that the route of intracellular expression is very efficient
      and superior to the one which results in secretion of IL-1 beta. This indicates
      that the use of B. subtilis as a recombinant host in biotechnology is not
      strictly dependent on its ability to secrete proteins into the culture medium.

PMID- 1367532
TI  - Dried gel hybridization in place of southern hybridization for detection of
      Listeria monocytogenes DNA fragments.
AB  - A simple, sensitive, dried gel DNA hybridization method for detection of Listeria
      monocytogenes DNA fragments is described. DNA samples were fractionated on an
      agarose gel. The gel was then denatured in NaOH-NaCl and neutralized in Tris
      NaCl. The resulting agarose gel was dried and hybridized with 32P-labelled DNA
      probe. No transfer to nitrocellulose membranes was used.

PMID- 1367531
TI  - Expression of the Bacillus subtilis levanase gene in Escherichia coli and
      Saccharomyces cerevisiae.
AB  - The gene coding for the inulin hydrolyzing enzyme levanase which was previously
      cloned from Bacillus subtilis was fused to the tac-promoter. Overexpression in
      Escherichia coli resulted in high amounts of intracellularly produced levanase
      (up to 20 U mg-1). After removal of the bacterial 5' sequences, the levanase gene
      was also cloned into a yeast expression vector based on the PGK-promoter. Clones
      containing the intact levanase gene including the bacterial signal sequence gave
      rise to synthesis of active levanase by Saccharomyces cerevisiae transformants. A
      considerable amount of levanase protein was found in the culture medium (around
      0.5 U ml-1) indicating efficient secretion of B. subtilis levanase from yeast.

PMID- 1367533
TI  - Isolation of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine from culture broths
      by covalent chromatography.
AB  - An efficient procedure for the isolation of reduced delta-(L-alpha-aminoadipyl)-L
      cysteinyl-D-valine (ACV) from culture supernatants of beta-lactam antibiotic
      producing microorganisms is described. The method utilises covalent
      chromatography to isolate thiols from culture broths that have been deproteinised
      and undergone borohydride reduction. 2-Pyridyl disulphide activated thiopropyl
      Sepharose was employed batchwise to isolate the thiols present in such broths
      from cultures of the known ACV excreter Cephalosporium acremonium N2 and the
      penicillin producer Penicillium chrysogenum P2. ACV was separated from these
      mixtures of thiols by gel permeation chromatography. Reversed-phase HPLC analysis
      showed the ACV to be of a high purity unless isolated from a highly complex
      culture medium.

PMID- 1367534
TI  - Production of pectin methylesterase from Erwinia chrysanthemi B374 in Bacillus
      subtilis.
AB  - The gene coding for pectin methylesterase (PME) of Erwinia chrysanthemi B374
      (pme) was cloned by a polymerase chain reaction. The pme gene was expressed in
      Bacillus subtilis using a secretion vector based on the promoter and signal
      sequence of the alpha-amylase gene from B. amyloliquefaciens. The cultivation of
      B. subtilis cells carrying the cloned pme resulted in efficient secretion of PME
      into the culture medium based on enzymatic and sodium dodecyl sulphate-poly
      acrylamide gel electrophoresis characterizations. The NH2-terminal sequence
      analysis of the secreted PME revealed two different NH2-termini. Heterologous
      processing was probably due to a second putative signal peptidase cleavage site
      at the joint region between the PME and alpha-amylase signal peptide.

PMID- 1367535
TI  - Reshaping a human monoclonal antibody to inhibit human respiratory syncytial
      virus infection in vivo.
AB  - We transferred the complementarity determining regions from a murine monoclonal
      antibody that neutralizes infection by respiratory syncytial virus (RSV) to a
      human IgG1 monoclonal antibody. The resulting reshaped human antibody lost
      affinity for RSV, but an additional alteration to one of the framework regions
      restored binding affinity and specificity. This second generation reshaped human
      monoclonal antibody cross-reacted with all clinical isolates of RSV tested and
      both prevented disease and cured mice even when administered four days after
      infection. We expect the antibody will prove useful in the management of this
      major childhood disease.

PMID- 1367536
TI  - Continuous regeneration of NAD(H) covalently bound to a cysteine genetically
      engineered into glucose dehydrogenase.
AB  - We introduced a cysteine residue on the surface of glucose dehydrogenase from
      Bacillus subtilis using site-directed mutagenesis. To this mutant, an NAD
      analogue was covalently attached by a disulphide bridge so that it was active
      intramolecularly. The glucose dehydrogenase-cys44-NAD complex, which contained
      one reactive NAD molecule per subunit of glucose dehydrogenase, was operated
      together with lactate dehydrogenase in a coupled enzymatic regeneration of NAD(H)
      in a hollow fiber reactor. L-lactate and gluconic acid were continuously produced
      from pyruvate and D-glucose, respectively, with a turnover number of 45 cycles
      per minute for each NAD molecule. The total turnover per coenzyme was 135,000 for
      the first 2.5 days.

PMID- 1367537
TI  - Broad host-range vector for efficient expression of foreign genes in gram
      negative bacteria.
AB  - A broad host-range expression plasmid was constructed comprising the incQ
      replicon, the recA promoter from Escherichia coli and the g10-L ribosome binding
      site (RBS) derived from bacteriophage T7. The structural genes for porcine
      somatotropin (pst) and E. coli beta-galactosidase (lacZ) were used to monitor
      gene expression in a diverse collection of Gram-negative bacterial hosts:
      Escherichia coli, Pseudomonas aeruginosa, Pseudomonas syringae, Pseudomonas
      putida, Pseudomonas fluorescens, Pseudomonas testosteroni, Serratia marcescens
      and Erwinia herbicola. The E. coli recA promoter was functional in this wide
      range of hosts and was inducible by the addition of nalidixic acid. Moreover, the
      level of lacZ expression was often at least as high as that observed in E. coli.
      Previous studies had shown that the g10-L RBS was superior to a simple
      "consensus" RBS sequence for expression of foreign genes in E. coli. Here we
      demonstrate a 38 to 70 fold increase in expression in two Pseudomonas hosts using
      the g10-L RBS, indicating that the translational enhancer present in the g10-L
      RBS is also functional in other bacteria. The juxtaposition of these
      transcriptional and translational elements in a broad host-range vector provides
      a simple way to evaluate alternate hosts for recombinant protein production.

PMID- 1367538
TI  - High level expression of human tissue-type plasminogen activator gene in mouse
      C127 cell.
AB  - We have expressed human tissue plasminogen activator (t-PA) gene at high levels
      in a mouse cell line. The t-PA cDNA with deletion of the long 3' untranslated
      region was inserted into a bovine papilloma virus (BPV) derived vector under the
      control of a mouse metallothionein promoter. The mouse metallothionein (mMT) gene
      also provided signals for splicing and polyadenylation. Mouse C127 cells
      transfected with this construct secreted t-PA at high levels into the cell
      culture medium. When an SV40 polyadenylation signal was inserted between the t-PA
      cDNA and the mMT splicing signals, the expression level increased by several
      fold. The expression levels did not increase further upon either introduction of
      Rous sarcoma virus LTR into the plasmid or mutation of the translation initiation
      context sequence to conform with the consensus one. Most of the plasmid appears
      to be integrated into the host chromosome. Cells producing high levels of t-PA
      tend to detach from the dish in a few days after passage. When grown on porous
      microcarriers, however, such cells can be maintained in culture for months and t
      PA can be harvested continuously.

PMID- 1367539
TI  - On-line determination of intracellular beta-galactosidase activity in recombinant
      Escherichia coli using flow injection analysis (FIA).
AB  - A flow injection analysis (FIA) system was developed for the determination of
      cytoplasmic beta-galactosidase activity in recombinant Escherichia coli. The FIA
      system and its application for on-line monitoring of beta-galactosidase
      production during cultivation of recombinant E. coli in a 60-l airlift tower loop
      reactor is described. The results demonstrate that an FIA assay in conjunction
      with a cell disintegration step can be applied successfully for on-line
      monitoring of intracellular protein formation.

PMID- 1367540
TI  - Molecular cloning in Lactobacillus helveticus by plasmid pSA3::pVA797 co
      integrate formation and conjugal transfer.
AB  - A gene encoding beta-glucanase activity from Bacillus amyloliquefaciens was
      subcloned in both orientations into plasmid shuttle vector pSA3. In only one
      orientation could a co-integrate be generated with the conjugative plasmid
      pVA797. The plasmid co-integrate was conjugated into Lactobacillus helveticus
      strain CNRZ450, where it was stably maintained without antibiotic selection and
      exhibited beta-glucanase activity. This method of introducing cloned DNA into
      thermophilic lactobacilli will facilitate the study of heterologous gene
      expression in non-transformable species.

PMID- 1367541
TI  - Respiratory activity of alginate-encapsulated Pseudomonas fluorescens cells
      introduced into soil.
AB  - Alginate-entrapped cells of Pseudomonas fluorescens were introduced into soil
      microcosms to evaluate their respiratory activity (O2 consumption and CO2
      evolution) and survival during a 14-day incubation period at 20 degrees C.
      Alginate-entrapped cells and cells resuspended in sterile distilled water and
      introduced into sterile soil exhibited relatively similar O2 consumption/CO2
      evolution and survival over the 14-day period. The same treatments in non-sterile
      soil exhibited lower respiratory activity and a population density decrease of
      about 2.0 Log. cfu/g after 14 days. Alginate-entrapped bacterial cells may be a
      useful method for introducing genetically-engineered and non-engineered bacterial
      strains into the soil environment.

PMID- 1367542
TI  - Imaging with simultaneous DIC and fluorescence microscopy.

PMID- 1367543
TI  - Screening of staphylococci for the toxic shock syndrome toxin-1 (TSST-1) gene.
AB  - Dot blot hybridization was used to screen 820 staphylococci for the presence of
      the gene coding for TSST-1. The DNA of 33 strains among 70 Staph. aureus strains
      isolated from suspected toxic shock syndrome (TSS) cases hybridized with the
      probe. These results agreed perfectly with those obtained with a phenotypic
      method (immunodiffusion). Among 608 Staph. aureus strains isolated over a period
      of one month from hospitalized patients, 66 (11%) hybridized with the probe; of
      these strains, 64 (97%) were found to produce TSST-1 in vitro. None of 145
      coagulase-negative staphylococcal strains harboured DNA hybridizing with the
      probe. The data indicate that this genotypic assay is suitable for
      epidemiological studies.

PMID- 1367544
TI  - Transgenic production of a variant of human tissue-type plasminogen activator in
      goat milk: generation of transgenic goats and analysis of expression.
AB  - We report the first successful production of transgenic goats that express a
      heterologous protein in their milk. The production of a glycosylation variant of
      human tPA (LAtPA--longer acting tissue plasminogen activator) from an expression
      vector containing the murine whey acid promoter (WAP) operatively linked to the
      cDNA of a modified version of human tPA was examined in transgenic dairy goats.
      Two transgenic goats were identified from 29 animals born. The first animal, a
      female, was mated and allowed to carry the pregnancy to term. Milk was obtained
      upon parturition and was shown to contain enzymatically active LAtPA at a
      concentration of 3 micrograms/ml.

PMID- 1367545
TI  - Transgenic expression of a variant of human tissue-type plasminogen activator in
      goat milk: purification and characterization of the recombinant enzyme.
AB  - A glycosylation variant of human tissue-type plasminogen activator (tPA)
      designated longer-acting tissue-type plasminogen activator (LAtPA) was
      extensively purified from the milk of a transgenic goat by a combination of acid
      fractionation, hydrophobic interaction chromatography and immunoaffinity
      chromatography. This scheme provided greater than 8,000-fold purification of the
      protein, a cumulative yield of 25% and purity greater than 98% as judged by SDS
      gel electrophoresis. SDS gel electrophoresis revealed that the transgenic enzyme
      was predominantly the "two chain" form of the protease. The specific activity of
      the purified transgenic protein, based on the average of the values obtained for
      three different preparations, was 610,000 U/mg as judged by amidolytic activity
      assay. This was approximately 84% of the value observed for the recombinant
      enzyme produced in mouse C127 cells. Analysis of the transgenic protein indicated
      that it had a significantly different carbohydrate composition from the
      recombinant enzyme produced in C127 cells. Molecular size analysis of the
      oligosaccharides from the transgenic and C127 cell-derived LAtPA preparations
      confirmed their differences and showed that the mouse cell-derived preparation
      contained larger, complex-type N-linked oligosaccharide structures than the
      material produced in goat mammary tissue.

PMID- 1367546
TI  - Cloning of the nitrate-nitrite reductase gene cluster of Penicillium chrysogenum
      and use of the niaD gene as a homologous selection marker.
AB  - A new homologous transformation system for the filamentous fungus Penicillium
      chrysogenum is described. The system is based on complementation of niaD mutants
      using the nitrate reductase structural gene (niaD) of P. chrysogenum. Spontaneous
      niaD mutants were identified after selection for chlorate resistance, in growth
      tests and subsequent complementation with the niaD gene of Aspergillus oryzae.
      The P. chrysogenum niaD gene was isolated from a genomic library using the
      Aspergillus nidulans niaD gene as a probe. After subcloning of the hybridizing
      fragment, the vector obtained, pPC1-1, was capable of transforming a P.
      chrysogenum niaD mutant at an average of 40 transformants per micrograms of
      circular DNA. Southern analysis of genomic DNA from a number of transformants
      showed that pPC1-1 DNA was integrated predominantly at sites other than the niaD
      locus. Using hybridization analysis it was shown that the niaD gene of P.
      chrysogenum is clustered with the nitrite reductase gene (niiA). From analysis of
      the nucleotide sequences of parts of the niaD and niiA genes of P. chrysogenum
      and comparison of these sequences with nucleotide sequences of the corresponding
      A. nidulans genes it was deduced that the P. chrysogenum genes are divergently
      transcribed.

PMID- 1367547
TI  - Use of the urokinase-type plasminogen activator gene as a general tool to monitor
      expression in transgenic animals: study of the tissue-specificity of the murine
      whey acidic protein (WAP) expression signals.
AB  - Urokinase-type plasminogen activator (uPA) is a proteolytic enzyme able to
      convert the zymogen plasminogen into the strong protease plasmin. The
      availability of very sensitive tests to measure the enzymatic activity of a
      plasminogen activator renders the corresponding gene an ideal candidate for the
      detection of promoter activity. In this paper we describe the utilization of the
      human uPA gene as detector of tissue-specificity of the murine whey acidic
      protein (WAP) expression signals in transgenic mice. The WAP promoter has been
      previously investigated for the production of foreign proteins in the milk of
      transgenic animals. In our genetic constructions, the human uPA cDNA was linked
      to the promoter region as well as to 3'-end distal sequences of the WAP gene.
      Five transgenic lines were obtained in which, however, expression levels of human
      uPA in the milk were still quite low. Surprisingly, four of these five positive
      transgenic mice show a consistent activity of the WAP promoter in brain extracts
      compared to other tissues.

PMID- 1367548
TI  - Action of a cell wall proteinase from Lactococcus lactis subsp. cremoris SK11 on
      bovine alpha s1-casein.
AB  - The cell wall-associated proteinase from Lactococcus lactis subsp. cremoris SK11
      was partially purified and incubated with alpha s1-casein for various times up to
      48 h. Sixteen trifluoroacetic acid-soluble oligopeptide hydrolysis products were
      identified by determination of the amino acid sequence. Eleven of these
      oligopeptides originated from the 78-residue sequence comprising the C-terminal
      region of alpha s1-casein and were present among the products after the first 60
      min of digestion. Three oligopeptides from the N-terminal region and two others
      from the central region of the alpha s1-casein sequence were also present among
      the early digestion products although in smaller amounts than most of the
      oligopeptides from the C-terminal region. No clear consensus sequence of amino
      acid residues surrounding the cleavage sites could be identified.

PMID- 1367549
TI  - Growth and protein production kinetics of a murine myeloma cell line transfected
      with the human growth hormone gene.
AB  - A model mammalian cell system for the production of recombinant proteins was
      investigated. Murine myeloma cells which had lost the ability to produce both
      heavy and light chain immunoglobulin molecules were transfected with a vector
      containing the immunoglobulin heavy chain promoter and enhancer elements linked
      to the human growth hormone gene. The growth kinetics of G32, a clonal isolate,
      were found to be similar to both the parent myeloma and hybridomas. However,
      production of hGH by G32 was growth associated, rather than as a secondary
      metabolite as is the case for hybridomas. In addition, G32 produced hGH at molar
      levels greater than most hybridomas.

PMID- 1367550
TI  - Single chain antibody variable regions.
AB  - The use of antibodies or antibody fragments for targeting tumors (either for
      tumor imaging or as carriers for drugs or toxins), has encountered problems of
      clearance, and non-specific or inefficient binding in clinical trials. A novel
      approach, linking two antibody variable fragments (Fvs), with a short peptide to
      generate a continuous polypeptide chain, may be able to overcome some of these
      problems. Since these single chain antibody variable regions (scFvs), are
      transcribed from constructed 'genes', large-scale production in, for example, E.
      coli, should be straightforward.

PMID- 1367552
TI  - Specificity of a cell-envelope-located proteinase (PIII-type) from Lactococcus
      lactis subsp. cremoris AM1 in its action on bovine beta-casein.
AB  - The action of the cell-envelope proteinase (PIII-type) from Lactococcus lactis
      ssp. cremoris AM1 on bovine beta-casein was studied. The results were compared
      with those obtained earlier with (PI-type) proteinases from the cell envelope of
      other L. lactis strains. From a 4-h digest (pH 6.2; 15 degrees C) of beta-casein
      made with the PIII-type proteinase, 24 peptides were isolated and purified by
      selective precipitation followed by semi-preparative reversed-phase HPLC.
      Altogether, these peptides accounted for the preferential splitting of 16 peptide
      bonds in beta-casein by the PIII-type proteinase. In nine cases the primary
      cleavage site (P1-P'1) was a Glx-X or X-Glx peptide bond. In ten cases at least
      one large hydrophobic residue (Met, Leu, Tyr, Phe) formed part of the cleavable
      bond. The P2-P3 and/or P'2-P'3 regions of the substrate consisted of hydrophobic
      and/or negatively charged side chains or of side chains potentially involved in
      hydrogen bonds. Nine of the peptide bonds split were reported previously to be
      also susceptible to cleavage by PI-type proteinases, although the kinetics may be
      different. The PIII-type proteinase shows a broader specificity in its initial
      cleavage of beta-casein than does the PI-type.

PMID- 1367551
TI  - Immobilization of microsomes into alginate beads is a convenient method for
      producing glucuronides from drugs.
AB  - The production of glucuronides from drugs by immobilized microsomal uridine
      diphosphate (UDP)-glucuronosyltransferase has been investigated. Of all the
      immobilization methods used (covalent binding, adsorption by ionic or hydrophobic
      interactions), only entrapment of microsomes into alginate beads in the presence
      of polyethyleneimine was effective in producing high glucuronidation rates, thus
      leading to the formation of large amounts of metabolites. The performance of the
      bioreactor was optimized with the drug 3'-azido-3'-deoxythymidine (AZT), active
      against the human immunodeficiency virus, as a model substrate of UDP
      glucuronosyltransferase. Calcium (12 mM) could optimally improve the stability of
      microsomes entrapped in alginate beads. Upon immobilization, enzyme activation
      occurred, leading to a fivefold increase in specific activity. The determination
      of apparent Km and Vmax revealed that AZT was a better substrate for the
      immobilized enzyme than free microsomes. The AZT-glucuronide production obtained
      after 6 h was threefold higher than that observed with free microsomes. This
      bioreactor was also efficient in production of glucuronides from structurally
      different compounds such as bilirubin, 4-nitrophenol, clofibric acid, pirprofen,
      dextrorphan or morphine, the corresponding glucuronide of which possesses
      pharmacological or toxicological interest.

PMID- 1367554
TI  - Laboratory vacuum use and concurrent problems.

PMID- 1367553
TI  - Continuous production of tissue plasminogen activator (t-PA) by human embryonic
      lung diploid fibroblast, IMR-90 cells, using a ceramic bed reactor.
AB  - Ceramic pieces composed of 99.5% Al2O3, 3 to 6 mm long, were found to be a good
      matrix for growth of the human embryonic lung diploid fibroblast, IMR-90 cells.
      The tissue plasminogen activator (t-PA) was secreted in DME medium containing
      proteose peptone as a t-PA inducer. In addition, production of t-PA was enhanced
      by increasing extracellular CaCl2, from 3.6 to 5.4 mM. In order to eliminate
      negative feed-back control caused by t-PA produced and thus raise productivity,
      perfusion cultivation was performed using a ceramic-packed bed column, with a
      recirculating vessel. The recirculating vessel was used to mix fresh medium with
      spent medium, and to control dissolved oxygen concentrations in the extracellular
      environment by stirring. In continuous production using the packed bed column
      with 2 kg of ceramics (phi = H = 150 mm), increasing dilution rate to 0.5 day-1
      could reduce product inhibition at 3-4 x 10(5) cells/ml. Cellular productivity of
      560 IU/10(6) cells/day was obtained over 40 days and corresponded to the
      volumetric productivity of 183 IU/ml/day.

PMID- 1367555
TI  - Cesium chloride gradients in carbon fiber fixed angle rotor for purification of
      viruses, organelles, and plasmid DNA.

PMID- 1367556
TI  - A method for purifying IgM, IgA, IgE, IgG1, and other monoclonal antibodies.

PMID- 1367557
TI  - Are media just media? (Part II).

PMID- 1367558
TI  - Analysis of inositol phosphates.

PMID- 1367559
TI  - PCR and optical trapping may team up for single cell genetic screening. First
      target: replacing amniocentesis.

PMID- 1367560
TI  - Serum traceability.

PMID- 1367561
TI  - Long-term cultivation of mammalian cells.

PMID- 1367562
TI  - Accelerated degradation testing.

PMID- 1367563
TI  - Stabilizing proteins ... with hybrid vigour.

PMID- 1367564
TI  - Biosensors--a swell response to sugar.

PMID- 1367565
TI  - Stabilizing protein products: reflections on the glassy state.

PMID- 1367567
TI  - The kinetics of plasmid loss.
AB  - Instability of bacterial cloning vectors can present a serious problem when
      direct selection for plasmid-encoded phenotypes is undesirable, ineffective or
      impractical. Antibiotic selection may provide a satisfactory solution in enclosed
      fermentors but not where recombinant organisms are part of complex microbial
      consortia after release into the outside environment. In the past decade there
      has been significant progress towards understanding the causes of plasmid loss
      and the lessons learned from these studies can be used in the design of a new
      generation of stable vectors.

PMID- 1367566
TI  - pH gradients and membrane transport in liposomal systems.

PMID- 1367568
TI  - Strategies for improving plasmid stability in genetically modified bacteria in
      bioreactors.
AB  - Exploitation of recombinant organisms for the large-scale, commercial production
      of foreign proteins is often hampered by the problem of plasmid instability. A
      wide range of strategies have been reported for improving the stability of
      recombinant organisms. A combination of manipulating both the genetic design of
      recombinants and the conditions of culturing the organisms may be used to achieve
      stable host-vector associations during culture of recombinant organisms in
      bioreactors.

PMID- 1367569
TI  - The nasal delivery of peptides and proteins.
AB  - Many drugs of the future will be therapeutically active peptides and proteins
      developed through recombinant-DNA technology. A major factor limiting their
      exploitation is the current lack of appropriate non-parenteral delivery systems.
      Nasal systems incorporating absorption enhancers may provide a convenient,
      efficient means of administering protein and peptide therapeutics.

PMID- 1367570
TI  - Protein A insensitive ELISA detection of staphylococcal enterotoxin B.
AB  - A sandwich enzyme-linked immunosorbent assay to detect staphylococcal enterotoxin
      B was developed using rat monoclonal antibodies as capture antibodies and as a
      biotinylated conjugate. This test was sensitive, less than 1 ng/ml of enterotoxin
      B was detected and interference by protein A was prevented by the use of rat
      monoclonal antibodies of the IgG2a isotype which were insensitive to protein A
      even at concentrations greater than 1000 ng/ml.

PMID- 1367571
TI  - Monitoring of the production of monoclonal antibodies by hybridomas. Part I: Long
      term cultivation in hollow fibre bioreactors using serum-free medium.
AB  - The long-term cultivation of hybridoma cells in hollow fibre bioreactors using
      serum-free medium, was monitored with respect to quantitative and qualitative
      aspects of the produced mAbs, cell viability, LDH and proteolytic activity.
      During the culture periods of hybridoma cells producing mAb OT-1C and 3A, the mAb
      concentration showed a decreasing trend with a concomitant increase of IgG
      fragments. The major IgG fragments did not bind the antigen and the molecular
      weights were significantly different from the corresponding IgG heavy and light
      chains. In addition, a good correlation was found between cell lysis, the
      presence of acid protease(s) and IgG fragments. The physicochemical and
      immunochemical properties of the "intact" mAbs (such as molecular weights, IEF
      patterns and affinity) did not change significantly during the culture period.

PMID- 1367572
TI  - Monitoring of the production of monoclonal antibodies by hybridomas. Part II:
      Characterization and purification of acid proteases present in cell culture
      supernatant.
AB  - An acid proteolytic activity has been found in cell culture supernatants from
      long-term cultivations of hybridoma cells in hollow fibre bioreactors using serum
      free medium. The proteolytic activity has now been further characterized and the
      main results were: (1) the proteolytic activity showed a maximum around pH 3 and
      declined essentially to zero at pH 8; (2) the activity was specifically inhibited
      by pepstatin A; (3) the acid proteases consisted of two sets of closely spaced
      bands with apparent molecular weights of 40-45K and 90-105K, respectively; (4)
      the protease bands (40-45K and 90-105K) were reactive with anti-human cathepsin
      D; (5) the IEP values of the acid proteases ranged from pH 4.55-6.5. Furthermore,
      IgG incubation with the acid proteases isolated from hybridoma cells yielded
      fragments similar to those found in serum-free hollow fibre cell culture
      supernatants. These results indicated that the IgG fragments are the result of
      degradation by cathepsin D like proteases released after cell death or cell
      lysis.

PMID- 1367574
TI  - Production of functional IgM Fab fragments by Saccharomyces cerevisiae.
AB  - The aim of this study was to express and secrete functional mouse IgM fragments
      in yeast. The heavy chain cDNA was truncated at two different sites, yielding
      genes coding for the complete VH domain. In one of the truncated genes, the CH1
      domain is complete, while in the other gene 18 bp are missing from the 3'
      terminus of the CH1 region. Both shortened genes were coexpressed in
      Saccharomyces cerevisiae with a cDNA gene encoding a full length mouse Ig light
      chain. We show that only the longer form of the truncated heavy chain together
      with the light chain produced and secreted functional IgM Fab fragments.

PMID- 1367573
TI  - Activation of ergot alkaloid biosynthesis in prototrophic isolates by Claviceps
      purpurea protoplast fusion.
AB  - Intraspecific protoplast fusions were carried out with active ergocornine
      ergokryptine and inactive ergocristine Claviceps purpurea strains and vice versa.
      The isolated prototrophic strains from both types of crossings produced all three
      alkaloid types, showing that biosynthesis of distinct alkaloid was activated in
      an inactive partner strain. The prototrophic isolates were stable on minimal
      medium but they segregated by subculturing on complete medium. In comparison with
      the original partner strains, differences in morphological and cytological
      characteristics were also established.

PMID- 1367575
TI  - IgG production in hybridoma batch culture: kinetics of IgG mRNA, cytoplasmic-,
      secreted- and membrane-bound antibody levels.
AB  - During batch cultivation of the I.13.17. hybridoma cell line, there is a 15 to 20
      fold decrease in the levels of cytoplasmic and membrane-bound mAb, and a 7 to 10
      fold decrease in the cellular levels of kappa and gamma chain mRNAs, as the cells
      pass from the exponential into the decline phase of growth. The profile of the
      specific mAb production rate does not correlate with the kinetics of either the
      cytoplasmic mAb or the specific mRNAs throughout the culture. Flow cytometry
      analyses have revealed that dead cells, which account for 40 to 70% of total
      cells during the decline phase, might significantly interfere with the
      determination of cytoplasmic mAb levels of cell-lysates ELISA and with the
      calculation of the specific mAb production rate. Possible influences of these
      parameters on mAb synthesis and secretion during hybridoma batch culture are
      discussed.

PMID- 1367576
TI  - Inducible high-level expression of heterologous genes in Bacillus megaterium
      using the regulatory elements of the xylose-utilization operon.
AB  - We have constructed a shuttle plasmid for Bacillus megaterium and Escherichia
      coli that contains the promoter and repressor gene of the B. megaterium-borne
      operon for xylose utilization. A polylinker downstream of the promoter allows
      versatile cloning of genes under its transcriptional control. We have placed gdhA
      (encoding glucose dehydrogenase) from B. megaterium, lacZ (encoding beta
      galactosidase) from E. coli, mro (encoding mutarotase) from Acinetobacter
      calcoaceticus, and human puk (encoding single-chain urokinase-like plasminogen
      activator, rscuPA) under xylose control in this vector. All four genes were
      between 130-fold and 350-fold inducible by 0.5% xylose in the growth medium in B.
      megaterium. Enzymatically active glucose dehydrogenase and mutarotase accumulated
      to 20% and 30% of the total soluble protein, respectively. beta-Galactosidase and
      rscuPA were also expressed at a high level. A gel analysis of the products
      demonstrated their proteolytic stability in the cytoplasm, even up to 5 h after
      induction. The expression properties of this new host-vector system are discussed
      in comparison to the ones available for B. subtilis and E. coli.

PMID- 1367577
TI  - Gene cloning of the maoA gene and overproduction of a soluble monoamine oxidase
      from Klebsiella aerogenes.
AB  - We cloned the structural gene for monoamine oxidase (maoA) from Klebsiella
      aerogenes into a pKI212 vector in an maoA mutant strain of K. aerogenes. Deletion
      analysis and complementation tests of the recombinant plasmid showed that the
      maoA gene was located entirely within a 4.1-kb segment. In an maoA mutant strain
      harbouring the cloned maoA gene, synthesis of monoamine oxidase was induced by
      addition of tyramine and related compounds. Transfer of a plasmid containing the
      maoA gene into a monoamine oxidase-producing strain of K. aerogenes W70 resulted
      in about a 30- to 40-fold increase in total production of the enzyme. When cells
      of K. aerogenes carrying the plasmid containing the maoA gene were grown with
      tyramine, more than 85% of the monoamine oxidase was produced in soluble form,
      whereas the parent strain W70 produced most monoamine oxidase as the membrane
      bound form.

PMID- 1367578
TI  - Inactivation of recombinant plasmid DNA from a human erythropoietin-producing
      mouse cell line grown on a large scale.
AB  - Experiments were carried out to assess the survival of recombinant plasmid DNA
      during large-scale production of recombinant human erythropoietin (rhuEPO) in a
      fermentation pilot plant. The analyses revealed DNA-degrading activities in the
      fermentation broth and in the waste-water, leading to rapid destruction of
      plasmid DNA added to medium or waste-water. The capability of the plasmid-DNA
      spiked samples to transform competent bacteria was drastically reduced. The DNA
      degrading activity in the waste-waters could be blocked by addition of EDTA or by
      boiling, indicating the presence of DNA-degrading enzymes (DNases). No plasmid
      specific DNA sequences were detected in waste-water samples by in-vitro
      amplification with Taq-polymerase. Genomic DNA preparations of cell debris
      collected from waste-water samples only contained degraded plasmid DNA.
      Furthermore, it was shown that intact plasmid DNA could be degraded to fragments
      of less than 1000 bp by incubation at 121 degrees C for 20 min, leading to a
      decrease in the plasmid-specific transforming capacity by a factor of 10(3) per
      minute. Thus, DNA from the rhuEPO production pilot plant was efficiently
      inactivated at three different levels: (i) in the fermentation medium (DNase),
      (ii) in the waste-water container (DNase), and (iii) by heat inactivation for 20
      min at 120 degrees C. These results indicate that the probability of delivery of
      recombinant DNA into the environment is extremely low in such biotechnological
      production processes.

PMID- 1367579
TI  - Expression of the core antigen gene of hepatitis B virus (HBV) in Acetobacter
      methanolicus using broad-host-range vectors.
AB  - Using the broad-host-range promoter probe vector pRS201 for cloning of phage Acm1
      promoters, we established a convenient vector system for expression of
      heterologous genes in different Gram-negative bacteria. The usefulness of this
      system was demonstrated by expression of the HBV core gene in Acetobacter
      methanolicus. Plasmids carrying the HBV core gene downstream of different Acm1
      phage promoters were transferred to A. methanolicus, a new potential host for
      recombinant DNA expression. Using enzyme immunoassay and immunoblot techniques,
      the amount and composition of core antigen produced in A. methanolicus were
      compared with that derived from Escherichia coli. The expression of
      immunoreactive core antigen in A. methanolicus exceeds by sevenfold that in E.
      coli using an expression system with tandemly arranged promoters. Morphological
      observations by electron microscopy show that the HBV core gene products isolated
      from both hosts are assembled into regular spherical particles with a diameter of
      about 28 nm that are comparable to original viral nucleocapsids.

PMID- 1367580
TI  - Biodegradation of 4-chlorophenol by adsorptive immobilized Alcaligenes sp. A 7-2
      in soil.
AB  - Alcaligenes sp. A 7-2 immobilized on granular clay has been applied in a
      percolator to degrade 4-chlorophenol in sandy soil. Good adsorption rates on
      granular clay were achieved using cell suspensions with high titres and media at
      pH 8.0. The influence of various parameters such as aeration rate, pH,
      temperature, concentration of 4-chlorophenol and size of inoculum on the
      degradation rate were investigated. During fed-batch fermentations under optimal
      culture conditions, concentrations of 4-chlorophenol up to 160 mg.l-1 could be
      degraded. Semicontinuous culture experiments demonstrated that the degradation
      potential in soil could be well established and enhanced by the addition of
      immobilized bacteria. Continuous fermentation was performed with varying 4
      chlorophenol concentrations in the feed and different input levels. The maximum
      degradation rate was 1.64 g.l-1.day-1.

PMID- 1367582
TI  - Microinjection technology--applications and procedures.

PMID- 1367581
TI  - Gene mapping by optical microscopy.

PMID- 1367583
TI  - Protein separations on tentacle ion exchangers.
AB  - This study was undertaken to introduce new tentacle ion exchange materials to the
      biochromatographer. The differences in the bioseparation media have been shown
      with a four-component protein mixture. By controlling the sample loading and the
      flow rate, each material can be made to perform satisfactorily, according to the
      demands of the biochromatographer, whether for high resolution or high sample
      capacity. The controlled manufacturing techniques of the Fractogel and
      LiChrospher DEAE materials make any analytical or process separations equivalent
      and reproducible. When even higher capacities are required, the
      biochromatographer need only use the wider diameter Superformance glass columns
      packed with the equivalent Fractogel.

PMID- 1367584
TI  - International Electrophoresis Society '91: never the twain shall meet?

PMID- 1367585
TI  - Monoclonal antibody enhancement in protein-free and serum-supplemented hybridoma
      culture.

PMID- 1367586
TI  - A butyrolactone lignan disaccharide from Flacourtia ramontchi.
AB  - beta-Sitosterol, beta-sitosterol-beta-D-glucopyranoside and a butyrolactone
      lignan disaccharide, ramontoside, were isolated from the heartwood of Flacourtia
      ramontchi. The structure of ramontoside was determined as diphyllin-4-O-[beta-D
      glucopyranosyl(1---4)]-beta- 2,3-di-O-methyl-D-xylopyranoside by hydrolysis and
      spectral data.

PMID- 1367587
TI  - Cyanohydrin glycosides with unusual sugar residues: revised structure of
      passitrifasciatin.
AB  - The cyclopentanoid cyanohydrin glycoside passitrifasciatin was reisolated, and
      shown to be (1S,4R)-1-(beta-D-gluopyranosyloxy)-4-(6-deoxy-beta-D-allopyran 
      osyloxy)-2-cyclopentene-1-carbonitrile, using one- and two dimensional NMR
      spectroscopy, selective acid-catalysed cleavage of the glycosidic linkage of 6
      deoxy-D-allose, and optical rotation data.

PMID- 1367588
TI  - Four triterpenoid saponins from dried roots of Gypsophila species.
AB  - Four new triterpenoid saponins were isolated from the roots of Gypsophila
      paniculata and G. arrostii. Their structures were elucidated using a combination
      of homo- and heteronuclear 2D NMR techniques, without having recourse to chemical
      degradation or modification. The saponins investigated are: 3-O-beta-D
      galactopyranosyl-(1----2)-[beta-D-xylopyranosyl-(1----3)]-bet a-D-
      glucuronopyranosyl quillaic acid 28-O-beta-D-glucopyranosyl-(1----3)-[beta-D
      xylopyranosyl-(1----4)]-alph a- L-rhamnopyranosyl-(1----2)-beta-D-fucopyranoside;
      3-O-beta-D-galactopyranosyl-(1----2)-[beta-D-xylopyranosyl-(1----3)]-bet a- D
      glucuronopyranosyl quillaic acid 28-O-beta-D-arabinopyranosyl-(1----4)-beta-D
      arabinopyranosyl++ +-(1----3)-beta-D- xylopyranosyl-(1----4)-alpha-L
      rhamnopyranosyl-(1----2)-beta-D-fucopyran oside; 3-O-beta-D-glucopyranosyl-(1---
      2)-beta-D-glucuronopyranosyl gypsogenin 28-O-beta-D-glucopyranosyl-(1----3)-[beta
      D-xylopyranosyl-(1----4)]-alph a- L-rhamnopyranosyl-(1----2)-beta-D
      fucopyranoside; 3-O-beta-D-xylopyranosyl-(1----3)-[beta-D-galactopyranosyl-(1---
      2)]-bet a- D-glucuronopyranosyl gypsogenin 28-O-beta-D-glucopyranosyl-(1----3)
      [beta-D-xylopyranosyl-(1----4)-alpha -L- rhamnopyranosyl-(1----2)-beta-D
      fucopyranoside.

PMID- 1367589
TI  - Steroidal and phenolic constituents of Lilium speciosum.
AB  - Phytochemical examination of the fresh bulbs of Lilium speciosum forma vestale
      has led to the isolation of a new phenolic glycoside and a new steroidal saponin.
      The respective structures of the new compounds have been shown by spectral
      analysis to be 6'-O-feruloylsucrose and (25R,26R)-26-methoxyspirost-5-en-3 beta
      o1 3-O-alpha-L-rhamnopyranosyl-(1----2)-beta-D-glucopyranoside. Several known
      phenolic glycosides and saponins have also been isolated and identified.

PMID- 1367590
TI  - Streptomycin-resistant mutant production in a continuous-flow UV mutation device.
AB  - A continuous-flow UV-induced mutation device which incorporates starting strain
      cultivation, UV irradiation and mutant reproduction was conceptualized and tested
      in this study using streptomycin resistance as an indicator of mutant production.
      For the experimental conditions employed and populations used, the mutation
      frequency for streptomycin resistance ranged from 10(-4) to 10(-5) cfu/ml. These
      mutation frequencies are comparable with conventional batch UV mutation methods
      and represent a gain of 3 orders of magnitude over the spontaneous mutation
      frequency.

PMID- 1367591
TI  - The use of particle concentration fluorescence immunoassay technology for the
      analysis of rDNA products.
AB  - The electrophoretic and immunological techniques typically used to detect
      potentially useful biopharmaceutical proteins are sensitive with detection limits
      in the nanogram range. However, quantitation of a recombinant protein can be
      cumbersome, and involve large numbers of samples throughout process optimization
      schemes. Although electrophoretic methods (i.e., SDS-PAGE and Western blots) now
      avail themselves to quantitation by densitometry, these techniques are time
      consuming because of the lack of appropriate automated systems. Biological
      activity assays, when available, often require relatively pure material and are
      not suitable for analyzing and quantitating impure or semi-purified samples,
      typical of the fermentation milieu. The optimization of several rDNA-derived
      protein systems from both prokaryotic and eukaryotic hosts has been completed
      using PCFIA, a rapid, sensitive system with high throughput. The development of
      Particle Concentration Fluorescence Immunoassay (CFIA) procedures for several of
      these rDNA-derived proteins of interest as potential biopharmaceuticals (e.g.,
      alpha-1-antitrypsin, tPA, soluble CD4, and a malaria vaccine candidate) are
      discussed.

PMID- 1367592
TI  - Use of continuous-flow UV-induced mutation technique to enhance chlorinated
      organic biodegradation.
AB  - In this study, a continuous-flow UV-induced mutation (CUM) device and the CUM
      device coupled to a selector (CUMS) reactor were fabricated and tested for their
      ability to enhance the probability of obtaining populations capable of
      chlorinated organic biodegradation. A mixed culture of bacteria were used as the
      starting strain for both the CUM and CUMS processes. Populations were obtained
      from the CUM and CUMS systems capable of 4-chlorobenzoic acid, 2,4
      dichlorobenzoic acid and chlorendic acid biodegradation. Non-UV irradiated
      population served as controls for the experiments and did not demonstrate
      chlorinated organic biodegradation over the test duration.

PMID- 1367594
TI  - Feedback regulation in preparative elution chromatography.
AB  - Input-output models utilizing discrete variables are developed for elution
      chromatography and used together with control theory to investigate behavior
      patterns between output variables (e.g., yield, purity, and production rate) and
      input variables (e.g., cut point locations and feed slug size). Variable
      interactions and controllability characteristics for isocratic and stepwise
      gradient elution in linear and nonlinear chromatography are investigated by using
      the relative gain array, singular value decomposition, and direct simulation.
      Inverse-based regulatory systems are evaluated for updating process inputs by
      using information on process outputs such that product quality and system
      performance parameters are efficiently maintained for the case where the column
      is overloaded and the solute peaks overlap with each other. Strategies for
      feedback optimizing control are also discussed.

PMID- 1367593
TI  - Studies on scale-up parameters of an immunoglobulin separation system using
      protein A affinity chromatography.
AB  - Effects of operational and system parameters on process scale-up of murine
      immunoglobulin (IgG2a kappa) purification using Protein A affinity chromatography
      are investigated. Parameters studied are those related to sample application,
      elution, ligand concentration on support, and column size change. Between sample
      application velocities of 0.004 and 0.030 cm/s (16-108 cm/h), the product
      concentration profiles in eluate did not show significant differences. With given
      system parameters, the retention time and bandwidth of the peak could be
      predicted by moment theory. The mean equilibrium constant during elution showed a
      strong effect of pH between 2 and 4. Within the range of protein A concentrations
      studied, 0.15-1.22 mg/mL of gel, the column capacity shows a linear relationship
      with the concentration of protein A immobilized. Dimensional scale-up of the
      column in the radial direction increased the total purification capacity linearly
      as the cross-sectional area increased without increasing pressure drop; however,
      the product concentration was diluted. Scale-up of the column dimension in the
      axial direction enables higher concentrations of product in the eluate, although
      the retention time increases linearly as the gel height increases.

PMID- 1367595
TI  - Improved adsorption to starch of a beta-galactosidase fusion protein containing
      the starch-binding domain from Aspergillus glucoamylase.
AB  - We have previously shown (Chen et al., 1991) that a beta-galactosidase (beta-gal)
      fusion protein (BSB133) containing 133 amino acids (aa) from the C-terminus of
      Aspergillus glucoamylase (GA) adsorbs strongly to starch compared to beta-gal,
      due to the presence of the GA starch-binding domain. We have now made deletions
      at the N-terminus of this 133-aa region to test the minimal size required for
      starch binding of beta-gal fusion proteins. Three fusion proteins (BSB119,
      BSB103, and BSB80) were genetically engineered, containing 119, 103, and 80 C
      terminal aa from GA, respectively. The fusion proteins were expressed in
      Escherichia coli and purified. Purified BSB119 adsorbed to native starch at least
      2-fold more strongly than did BSB133 or fusion proteins with shorter tails.
      Adsorption isotherms generated over a wide range of initial concentrations
      indicated a 10-fold difference in the loading capacity of starch for BSB119 (36.5
      mg of protein/g of starch) compared to beta-gal (3.7 mg of protein/g of starch).
      Adsorption constants calculated from the initial slopes of the isotherms
      indicated a nearly 30-fold difference in affinity to starch for BSB119 (Kad = 63
      mL/g of starch) compared to beta-gal (Kad = 2.3 mL/g of starch). BSB119 in the
      presence of crude enzyme extracts also bound to starch with a high affinity
      compared to a beta-gal control. Potential applications of the starch-binding tail
      include enzyme immobilization to starch or recovery and purification of target
      proteins from crude extracts.

PMID- 1367598
TI  - Biosensor principles and applications.

PMID- 1367597
TI  - Effect of dissolved oxygen control on growth and antibiotic production in
      Streptomyces clavuligerus fermentations.
AB  - A proportional-integral control system was used to control dissolved oxygen in a
      fermentor at constant shear and mass transfer conditions. Growth and antibiotic
      production in Streptomyces clavuligerus were studied at different dissolved
      oxygen levels during the fermentation. Three protocols were employed: no-oxygen
      control to provide a base case, oxygen controlled to a preset saturation level
      throughout the fermentation, and oxygen controlled at a high level only during
      the growth phase. The last protocol was aimed at optimizing the consumption of
      oxygen. Lower specific growth rates and cephamycin C yields were obtained when
      dissolved oxygen was controlled at 50% throughout the fermentation, compared to
      the base case. A 2.4-fold increase in the final cephamycin yield was observed
      when dissolved oxygen was controlled at saturation levels during the growth
      phase, compared to the experiments without dissolved oxygen control. This
      enhancement in yield was independent of the dissolved oxygen (DO) level after
      exponential growth, in the range of 50-100% saturation. The most effective
      control strategy, therefore, was to control DO only during active growth when the
      biosynthetic enzymes were probably synthesized.

PMID- 1367596
TI  - Long-term in vitro function of adult hepatocytes in a collagen sandwich
      configuration.
AB  - In an effort to reconstruct the cellular polarity normally found in the liver,
      adult rat hepatocytes were sandwiched between two layers of hydrated rat tail
      tendon collagen matrix. Functionally, sandwiched hepatocytes maintained the
      secretion of albumin, transferrin, fibrinogen, bile acids, and urea for at least
      6 weeks, whereas cells cultured on a single layer of collagen gel ceased such
      secretion in 1-2 weeks. After 1 week of culture on a single layer of collagen
      gel, hepatocytes could still recover these lost functions when a second layer of
      collagen gel was applied. The exact nature of the substrate for constructing the
      sandwich system appeared to be unimportant as long as it allowed cellular
      attachment. Hepatocytes cultured in the sandwich system appeared to maintain a
      distribution of actin filaments similar to the in vivo state, whereas cells
      cultured on a single layer of collagen gel showed abnormal formation of stress
      fibers. These studies suggest that simple manipulations of the configuration of
      extracellular elements can dramatically alter the behavior of cultured
      hepatocytes.

PMID- 1367599
TI  - What is a biosensor?

PMID- 1367600
TI  - Analytical applications of piezoelectric crystal biosensors.

PMID- 1367601
TI  - FET-based biosensors.

PMID- 1367602
TI  - Chemically mediated fiberoptic biosensors.

PMID- 1367603
TI  - Fluorophore- and chromophore-based fiberoptic biosensors.

PMID- 1367604
TI  - Bioluminescence- and chemiluminescence- based fiberoptic sensors.

PMID- 1367605
TI  - Immunosensors.

PMID- 1367606
TI  - Microbial biosensors.

PMID- 1367607
TI  - In vivo biosensors.

PMID- 1367608
TI  - Trends and prospects.

PMID- 1367609
TI  - Development of amperometric biosensors for enzyme immunoassay.

PMID- 1367610
TI  - Potentiometric enzyme electrodes.

PMID- 1367611
TI  - Amperometric enzyme electrodes for substrate and enzyme activity determinations.

PMID- 1367612
TI  - Enzyme thermistor devices.

PMID- 1367613
TI  - Peptide synthesis--theme and variations.

PMID- 1367614
TI  - Targeting peptides and proteins: NATO ASI.

PMID- 1367615
TI  - Protein sequences--homologies and motifs.

PMID- 1367616
TI  - Environmental regulation of bacterial virulence--implications for vaccine design
      and production.
AB  - There is now overwhelming evidence that many of the crucial virulence
      determinants of pathogenic bacteria are environmentally regulated and expressed
      only under certain conditions. Much progress is currently being made in
      identifying these factors and in understanding the molecular mechanisms
      controlling their production. This information is crucial for the understanding
      of microbial pathogenicity and it has important practical implications for
      vaccine design and production.

PMID- 1367617
TI  - Media additives for protecting freely suspended animal cells against agitation
      and aeration damage.
AB  - Over the past 30 years, several different additives have been used to protect
      freely suspended animal cells in culture from agitation and aeration damage.
      These include pluronic polyols, various derivatized celluloses and starches,
      protein mixtures, polyvinyl-pyrrolidones, dextrans, and, more recently,
      polyethylene glycol (PEG) and polyvinyl alcohol. The protective mechanisms of
      these additives are not yet fully understood, but recent studies suggest both
      fluid-mechanical and biological mechanisms of protection.

PMID- 1367618
TI  - Gray matter(s).

PMID- 1367619
TI  - Glial cells. The unsung heroes of the brain. One company's view.

PMID- 1367621
TI  - Biotechnology regulation in Europe.

PMID- 1367620
TI  - Black-market biotechnology: athletes abuse EPO and HGH.

PMID- 1367622
TI  - Molecular medicine: too much, too soon?

PMID- 1367623
TI  - Yeast systems for the commercial production of heterologous proteins.
AB  - Yeasts are attractive hosts for the production of heterologous proteins. Unlike
      prokaryotic systems, their eukaryotic subcellular organization enables them to
      carry out many of the post-translational folding, processing and modification
      events required to produce "authentic" and bioactive mammalian proteins. In
      addition, they retain the advantages of a unicellular microorganism, with respect
      to rapid growth and ease of genetic manipulation. The vast majority of yeast
      expression work has focused on the well-characterized baker's yeast Saccharomyces
      cerevisiae. However, with the development of DNA transformation technologies, a
      growing number of non-Saccharomyces yeasts are becoming available as hosts for
      recombinant polypeptide production. These include Hansenula polymorpha,
      Kluyveromyces lactis, Pichia pastoris, Schizosaccharomyces pombe, Schwanniomyces
      occidentalis and Yarrowia lipolytica. The performance of these alternative yeast
      expression systems is reviewed here relative to S. cerevisiae, and the advantages
      and limitations of these systems are discussed.

PMID- 1367624
TI  - Enzyme engineering for nonaqueous solvents: random mutagenesis to enhance
      activity of subtilisin E in polar organic media.
AB  - Enzyme activity is often dramatically reduced in polar organic solvents, even
      under conditions where the folded structures are stable. We have utilized random
      mutagenesis by polymerase chain reaction (PCR) techniques combined with screening
      for enhanced activity in the presence of dimethylformamide (DMF) to probe
      mechanisms by which improved enzymes for chemical synthesis in polar organic
      media might be obtained. Two amino acid substitutions which enhance subtilisin E
      activity in the presence of DMF, Q103R and D60N, were identified by screening on
      agar plates containing DMF and casein. The two substitutions are located near the
      substrate binding pocket or in the active site, and their effects on the
      catalytic efficiency kcat/KM for the hydrolysis of a peptide substrate are
      additive. The effects of D60N are apparent only in the presence of DMF,
      highlighting the importance of screening in the organic solvent. Protein
      engineering is an effective approach to enhancing enzyme activity in organic
      media: the triple mutant D60N + Q103R + N218S is 38 times more active than wild
      type subtilisin E in 85% DMF. An evolutionary approach consisting of multiple
      steps of random mutagenesis and screening in continually higher concentrations of
      organic solvent should result in enzymes that are substantially more active in
      organic media.

PMID- 1367625
TI  - Xylitol production by recombinant Saccharomyces cerevisiae.
AB  - We obtained efficient conversion of xylose to xylitol by transforming
      Saccharomyces cerevisiae with the gene encoding the xylose reductase (XR) of
      Pichia stipitis CBS 6054. Comparison of the chromosomal and cDNA copies of the
      XYL1 gene showed that the genomic XYL1 contains no introns, and an XR monomer of
      318 amino acids (35,985 D) is encoded by an open reading frame of 954 bp. The
      amino acid sequence of the P. stipitis XR is similar to several aldose
      reductases, suggesting that P. stipitis XR is part of the aldoketo reductase
      superfamily. S. cerevisiae transformed with the XYL1 gene gave over 95%
      conversion of xylose into xylitol, a yield not obtainable with natural xylose
      utilizing yeasts.

PMID- 1367626
TI  - Modular integrated fluidized bed bioreactor technology.
AB  - We describe the design and demonstrate the application of a modular integrated
      fluidized bed bioreactor system. Basically the system is a reactor vessel
      equipped with an extending cylinder and a liquid distributor plate. Instead of an
      external recirculation loop, as used in existing fluidized bed systems, a low
      shear stress impeller is used as the recirculation pump. The system has several
      unique features, such as modular exchangeable elements, efficient oxygenation and
      the option of operating as a stirred tank-, a packed bed- or a fluidized bed
      reactor. An example of a fluidized bed run using CHO-K1 cells is shown. Under
      standard culture conditions a 100-fold increase in cell density (up to 1.2 x
      10(8) cells/ml) was achieved.

PMID- 1367627
TI  - Evidence for T-DNA mediated gene targeting to tobacco chloroplasts.
AB  - The integration of foreign DNA into plant cells by Agrobacterium mediated
      transformation is random and normally directed at the nucleus. Here we present
      evidence that such transformation can be used to introduce foreign genes into
      higher plant chloroplasts by site-specific homologous recombination. A binary
      vector was made in vitro that included chloroplast ribosomal DNA (rDNA) within T
      DNA borders, and transgenic tobacco plants obtained using this construct were
      analyzed for the targeted recombination by hybridization, polymerase chain
      reaction (PCR) and DNA sequencing.

PMID- 1367628
TI  - Cancer immunoconjugates: will clinical success lead to commercial success?

PMID- 1367629
TI  - China's biotechnology in progress.

PMID- 1367630
TI  - Developing biotechnology opportunities in China.

PMID- 1367631
TI  - Media selection and design: wise choices and common mistakes.

PMID- 1367632
TI  - Structure and morphology of protein inclusion bodies in Escherichia coli.
AB  - We have studied the structure and characteristics of inclusion bodies formed by
      the enzyme beta-lactamase in the periplasmic space of Escherichia coli or in the
      cytoplasm, following expression of the protein without its signal sequence.
      Electron microscopy of highly purified protein aggregates using a novel sucrose
      gradient centrifugation procedure revealed striking morphological differences.
      Periplasmic inclusion bodies were essentially amorphous whereas the protein
      particles in the cytoplasm were highly regular. Depending on the cellular
      location, the inclusion bodies exhibited differences in protein composition even
      though they were formed by the expression of the same polypeptide chain. It was
      shown that the chaperonins GroEL and SecB are not incorporated into the inclusion
      bodies. Furthermore, the degree of solubilization of the inclusion bodies in the
      presence of denaturants and the sensitivity of the aggregated proteins to
      protease digestion indicated that the differences between cytoplasmic and
      periplasmic inclusion bodies extend to the conformation of the associated
      polypeptide chains.

PMID- 1367633
TI  - Mutations in human interferon gamma affecting inclusion body formation identified
      by a general immunochemical screen.
AB  - High level expression of the gene for human interferon-gamma (HuIFN-gamma) in E.
      coli JM101 cultured at 37 degrees C results in the distribution of over 90
      percent of the total accumulated gene product into inclusion bodies (IBs). We
      have identified mutations throughout the molecule that alter the distribution
      between the soluble and inclusion body fractions without greatly affecting total
      expression level. Some mutants retain high biological activity but are localized
      almost entirely in the soluble fraction. Mutations affecting IB distribution as
      well as stability to intracellular proteolysis were detected by immunochemical
      screens and verified by gel assays. Immunochemical screens such as those employed
      here may allow identification of folding and stability mutants in heterologously
      expressed proteins when there is no other basis for selection or screening. These
      results also suggest that one solution to production problems arising from IB
      formation may be to identify mutations in the target protein that favor
      expression of soluble protein while retaining biological activity.

PMID- 1367634
TI  - Enhancing the thermostability of glucose isomerase by protein engineering.
AB  - We have engineered recombinant glucose isomerase (GI) from Actinoplanes
      missouriensis by site-directed mutagenesis to enhance its thermal stability in
      both the soluble and immobilized forms. Substitution of arginine for lysine at
      position 253, which lies at the dimer/dimer interface of the GI tetramer,
      produced the largest stabilization under model industrial conditions. We discuss
      our results in terms of a model in which chemical glycation of lysines by sugars
      in the industrial corn syrup substrate represents a major pathway of
      destabilization.

PMID- 1367635
TI  - Protection against detrimental effects of potyvirus infection in transgenic
      tobacco plants expressing the papaya ringspot virus coat protein gene.
AB  - We obtained transgenic tobacco plants expressing the papaya ringspot virus (PRV)
      coat protein (CP) gene by transformation via Agrobacterium tumefaciens.
      Expression was effectively monitored by enzyme-linked immunosorbent assays
      (ELISA) of crude tissue extracts. Subcloned plants derived from eight original Ro
      transformants were inoculated with potyviruses: tobacco etch (TEV), potato virus
      Y (PVY), and pepper mottle (PeMV). Plants that accumulated detectable levels of
      the PRV CP showed significant delay in symptom development and the symptoms were
      attenuated. Similar results were obtained with inoculated R1 plants. We conclude
      that the expression of the PRV CP-gene imparts protection against infection by a
      broad spectrum of potyviruses.

PMID- 1367636
TI  - Purification and aqueous two-phase partitioning properties of recombinant
      Vitreoscilla hemoglobin.
AB  - Soluble recombinant Vitreoscilla hemoglobin was purified from E. coli lysate by
      sequential two-phase extraction techniques. Extraction of lysate containing VHb
      in PEG/dextran gave a 3.6-fold increase in VHb purity in the PEG-rich phase via a
      size exclusion mechanism. Further extraction of the recovered PEG phase in
      PEG/sodium sulfate gave an additional 2.0-fold increase in purity in the PEG-rich
      phase due to an electrostatic mechanism. Final extraction of the PEG phase in
      PEG/magnesium sulfate gave an additional 1.3-fold increase in VHb purity in the
      magnesium sulfate-rich phase. The final yield from the extractive purification
      was 47% with purity of VHb estimated to be greater than 95%. Yields from the
      sulfate salt extractions are essentially quantitative due to the extreme
      partitioning behavior of VHb in these systems. VHb partition coefficients as
      large as 46 in PEG/sodium sulfate and as small as 0.06 in PEG/magnesium sulfate
      were observed. Similar small partition coefficients were obtained with
      PEG/manganese sulfate extractions. This dramatic effect of divalent cation
      content on the partition coefficient of VHb in PEG/sulfate salt systems was
      investigated by pH and magnesium ion titration experiments. Results show the
      effect to be largest and nearly constant for pH values greater than 6.0 and
      diminished at lower pH values. A model based on magnesium ion binding to
      negatively charged amino acids is shown to correlate with the data well. Based on
      model formulation and the partitioning behavior of contaminant proteins, the
      observed effect is expected to be applicable to other proteins.

PMID- 1367637
TI  - Use of a stationary bed reactor and serum-free medium for the production of
      recombinant proteins in insect cells.
AB  - Insect cells (Spodoptera frugiperda) have been cultured in a stationary bed
      reactor, packed with a fibrous polyester carrier. When the bioreactor was
      perfused with serum-supplemented medium, a cell density of 6 x 10(6) cells ml-1
      packed carrier was reached. Scanning electron microscopy investigations have
      shown that the insect cells grew along the three-dimensionally oriented fibers of
      the Fibra-cel carrier. After infection of the logarithmically growing cells with
      a recombinant baculovirus (Autographa californica) containing the gene coding for
      beta-galactosidase, the medium in the bioreactor was changed to serum-free
      medium. At day 13 postinfection (p.i.), a beta-galactosidase level of 320
      microgram ml-1 and, at day 17 p.i., a virus titer of 2.1 x 10(8) TCID50 units ml
      1 (day 17 p.i.) were reached. In another bioreactor, operated in a similar way
      but with serum-containing medium, a beta-galactosidase concentration of 360
      microgram ml-1 and a virus titer of 2.3 x 10(8) TCID50 units ml-1 were obtained.
      These results indicate the potential use of this production system for the
      production of recombinant protein and baculovirus in insect cells.

PMID- 1367638
TI  - Hydrolytic reactions in two-phase systems. Effect of water-immiscible organic
      solvents on stability and activity of acid phosphatase, beta-glucosidase, and
      beta-fructofuranosidase.
AB  - The stability and activity of three hydrolytic enzymes, acid phosphatase (EC
      3.1.3.2), beta-fructofuranosidase (EC 3.2.1.26), and beta-glucosidase (EC
      3.2.1.4), were studied at 30 degrees C in two-phase systems. They were prepared
      with equal quantities of buffered water and a water-immiscible organic solvent.
      Low-molecular-weight acetates and paraffins were tested in this investigation.
      The kinetic constant of storage inactivation was correlated with the logarithm of
      solvent polarity. Enzyme stability in the presence of organic phases, whose log P
      value was included in 1.2-2.2, was greater than the one measured in pure buffered
      aqueous media. On the other hand, a dramatic enzyme denaturation took place
      making use of solvents at higher log P-value. Experiments carried out during the
      24-h operation clarified that the reaction yield does not depend solely on
      solvent polarity. Acid phosphatase and beta-glucosidase, which are less resistant
      than beta-fructofuranosidase to temperature and shear in buffered solutions,
      showed especially significant enhancement of catalytic activity when hydrolysis
      was performed with the addition of acetates (50% v/v).

PMID- 1367639
TI  - Cultivation of recombinant E. coli and production of fusion protein in 60-1
      bubble column and airlift tower loop reactors.
AB  - E. coli K12 with multicopy plasmid (lambda PR-promoter and temperature-sensitive
      lambda cI 857 repressor) was cultivated in 60-l bubble column and airlift tower
      loop reactors. The medium composition, cell concentration, and intracellulary
      enzyme activity were monitored on-line during batch, fed-batch, and continuous
      cultivations. The specific growth rates, cell mass yield coefficients, plasmid
      stabilities, productivities of the amount of active fusion protein (beta
      galactosidase activity), concentrations and yields of acetic acid, and volumetric
      oxygen transfer coefficient were evaluated for different medium compositions and
      cultivation conditions. The enzyme activity was also monitored during the
      temperature induction. The results evaluated in the 60-l bubble column and
      airlift tower loop reactors are compared with those evaluated in a 1-1 stirred
      tank reactor.

PMID- 1367640
TI  - Enzyme reaction engineering: design of peptide synthesis by stabilized trypsin.
AB  - By using very active and very stable trypsin agarose derivatives, we have
      optimized the design of the synthesis of a model dipeptide, benzoylarginine
      leucinamide, by two different strategies: (i) kinetically controlled synthesis
      (KCS), by using benzoyl arginine ethyl ester and leucinamide as substrates, and
      (ii) thermodynamically controlled synthesis (TCS), by using benzoyl arginine and
      leucinamide as substrates. In each strategy, we have studied the integrated
      effect of a number of variables that define the reaction medium on different
      parameters of industrial interest, e.g. time course of peptide synthesis, higher
      synthetic yields, and stability of the catalyst, as well as aminolysis/hydrolysis
      ratios and rate of peptide hydrolysis in the case of KCS. Both synthetic
      approaches were carried out in monophasic water or water-organic cosolvent
      systems. We have mainly tested a number of variables, e.g. temperature, polarity
      of the reaction medium (presence of cosolvents, presence of ammonium sulfate),
      and exact structure of the trypsin derivatives. Optimal experimental conditions
      for these synthetic approaches were established in order to simultaneously obtain
      good values for all industrial parameters. The use of previously stabilized
      trypsin derivatives greatly improves the design of these synthetic approaches
      (e.g. by using drastic experimental conditions: 1 M ammonium sulfate (KCS) or 90%
      organic cosolvents (TCS]. In these conditions, our derivatives preserve more than
      95% of activity after 2 months and we have been able to reach synthetic
      productivities of 180 (KCS) and 1 (TCS) tons of dipeptide per year per liter of
      catalyst.

PMID- 1367642
TI  - The Animal and Plant Cell Working Party of the European Federation of
      Biotechnology. R.E. Spier (Chairman), University of Surrey, UK, 3-4 December,
      1990.

PMID- 1367641
TI  - Immobilization of proteases to porous chitosan beads and their catalysis for
      ester and peptide synthesis in organic solvents.
AB  - alpha-Chymotrypsin (CT), subtilisin BPN' (STB), and subtilisin Carlsberg (STC)
      were immobilized by adsorption to porous chitosan beads (Chitopearl, CP). The
      immobilized enzymes showed higher catalytic activities than free enzymes for
      amino acid esterification in many hydrophilic organic solvents except for
      methanol and DMF. In ethanol, the initial rate of the esterification increased
      with water content, whereas in ethyl acetate, the maximum rate was obtained at 2%
      3% water. CP-immobilized CT also catalysed transesterification of Ac-Tyr-OMe in
      ethanol and peptide synthesis in acetonitrile from Ac-Tyr-OH or its ethyl ester
      and amino acid amides. The immobilized enzymes are highly stable in organic
      solutions, and can easily be separated from the reaction solutions. Repeated
      esterifications of Ac-Tyr-OH in acetonitrile by a CP-immobilized CT gave almost
      constant yields of the ester for more than 3 weeks.

PMID- 1367643
TI  - The effects of spore loading on the growth of Penicillium chrysogenum immobilised
      in kappa-carrageenan.
AB  - Penicillium chrysogenum spores were immobilised in kappa-carrageenan. The effect
      of the number of viable spores immobilised per bead on the rate of germination
      and degree of subsequent mycelial growth was investigated. The distribution of
      active mycelium throughout the bead was determined. At a high spore loading
      (10(3)-10(4) viable spores per bead) the biomass concentration was low and the
      majority of the actively respiring biomass was located at the bead periphery.
      Reducing the spore loading (to 50 viable spores per bead) resulted in a fourfold
      increase in immobilised biomass concentration. At very low spore loadings (5 and
      10 viable spores per bead) the concentration of biomass decreased, but mass
      transfer throughout the bead improved and the uniformity of active immobilised
      biomass increased. The spore loading also affected the morphology of the growing
      hyphae and the extent of free cell growth.

PMID- 1367644
TI  - Biotechnology: are there unique health and safety issues?

PMID- 1367645
TI  - Financing biotechnology.

PMID- 1367646
TI  - Tax incentive for Australian research and development.
AB  - The commercial rewards which can flow from the successful exploitation of R & D
      should encourage investment in biotechnological activities. Furthermore, the
      dynamic nature of biotechnology world-wide requires companies in the industry to
      constantly strive for significant advances which will provide them with a
      competitive advantage. In endeavouring to achieve such benefits, a significant
      cost saving may be available for a project which qualifies for the R & D tax
      concession. Accordingly, close consideration should be given to its availability
      and the conditions relevant to its eligibility.

PMID- 1367647
TI  - Victoria, a springboard for a research based pharmaceutical industry.

PMID- 1367648
TI  - All about licensing.

PMID- 1367649
TI  - Acetylation at O-2 of arabinofuranose residues in feruloylated arabinoxylan from
      bamboo shoot cell-walls.
AB  - Hydrolysis of bamboo shoot cell-walls with Driselase (a fungal enzyme
      preparation) gave an arabinoxylan trisaccharide with ferulic and acetic acids as
      ester groups. The structure of this oligosaccharide was determined to be O-[2-O
      acetyl-5-O-[E)-feruloyl)-alpha-L-arabinofuranosyl]-(1----3) -O-beta- D
      xylopyranosyl-(1----4)-D-xylopyranose, on the basis of spectroscopy and
      methylation analysis.

PMID- 1367650
TI  - Triterpene glycosides from Schefflera octophylla.
AB  - In addition to 3-epi-betulinic acid, three triterpene glycosides were isolated
      from leaves of Schefflera octophylla. The structures of the glycosides have been
      determined as 28-O-[alpha-L-rhamnopyranosyl(1----4)-O-beta-D-glucopyranosyl(1---
      6)-be ta-D- glucopyranosides of 3 alpha-hydroxy-lup-20(29)-ene-23,28-dioic acid,
      3 alpha,11 alpha- dihydroxy-lup20(29)-ene-23,28-dioic acid and 3-epi-betulinic
      acid by spectroscopic data and chemical transformations. The last two compounds
      were found for the first time in the plant kingdom.

PMID- 1367651
TI  - Triterpenoid glycosides from the bark of Mimosa tenuiflora.
AB  - Two new saponins were isolated from Mimosa tenuiflora and their structures
      established as 3-O-[alpha-L-rhamnopyranosyl(1----2)-beta-D-glucopyranosyl-(1---
      3]-(alp ha-L- arabinopyranosyl-(1----4]-beta-D-xylopyranosyl-(1----2)]-[beta-D-
      xylopyranosyl-(1----4)]-beta-D-glucopyranosyl)-28-O-alpha-L-rhamnopyrano syl
      oleanolic acid and 3-O-[alpha-L-rhamnopyranosyl-(1----2)-beta-D-glucopyranosyl-(1
      ---3]-(al pha- L-arabinopyranosyl-(1----4]beta-D-xylopyranosyl-(1----2)]-[beta-D-
      xylopyranosyl-(1----4)]-beta-D-glucopyranosyl) oleanolic acid.

PMID- 1367652
TI  - A betulinic acid glycoside from Schefflera venulosa.

PMID- 1367653
TI  - A saponin from callus tissue of Stauntonia hexaphylla.
AB  - A new 30-nortriterpenoid saponin was isolated from the callus tissues of
      Stauntonia hexaphylla. The structure of the saponin (tentatively named mubenoside
      A) was elucidated as 3 beta,20 alpha-dihydroxy-30-nor-olean-12-en-28-oic acid 3-O
      [beta-D-xylopyranosyl(1----2)-alpha-L-arabinopyranosyl(1----3) ]-beta-D-
      glucopyranoside by means of spectral experiments.

PMID- 1367654
TI  - A flavonol triglycoside from Actinidia arguta var. giraldii.
AB  - In the course of a chemotaxonomic study of the genus Actinidia a new flavonol
      triglycoside, quercetin 3-O-beta-D-[2G-O-beta-D-xylopyranosyl-6G-O-alpha-L
      rhamnopyranosyl] glucopyranoside was identified amongst the 15 flavonols found in
      Actinidia arguta var. giraldii. This compound was characterized, along with
      quercetin 3-O-beta-D-xylopyranosyl-(1-2)-O-beta-D-glucopyranoside, by 1H and 13C
      NMR spectroscopy. The kaempferol analogues were also isolated.

PMID- 1367655
TI  - Fetal-tissue research: abortion politics slow advances to a crawl.

PMID- 1367656
TI  - Patenting animals in Europe.

PMID- 1367657
TI  - People for people: the search consultant in biotechnology.

PMID- 1367658
TI  - Centrifugation takes a new turn.

PMID- 1367659
TI  - Engineering proteins to enhance their partition coefficients in aqueous two-phase
      systems.
AB  - We describe a novel method to partition recombinant proteins into the polymer
      rich top phase in poly(ethylene glycol) (PEG)4000/potassium phosphate aqueous two
      phase systems. The concept is based on fusion of a gene fragment encoding a short
      peptide sequence to the product gene of interest thereby changing the
      partitioning properties of the expressed product protein as a fusion to the
      peptide. The model protein in this study, ZZ, is a two domain molecule based on
      staphylococcal protein A (SPA) which distributes evenly in PEG/salt systems. A
      tetrapeptide sequence, AlaTrpTrpPro (designated the partitioning peptide), was
      designed by molecular modeling techniques to include exposed tryptophan residues
      and to have a coding DNA sequence which is possible to polymerize in an obligate
      head-to-tail fashion at the DNA level. Gene fragments encoding one and three
      partitioning peptides, respectively, were fused to the 3' end of the ZZ gene and
      the fusion proteins were produced intracellularly in Escherichia coli. The
      partition coefficients of ZZ proteins containing zero, one and three fused
      partitioning peptides were determined in three PEG 4000/potassium phosphate
      aqueous two-phase systems of different compositions. In all three phase systems,
      there were dramatic effects on the partition coefficient by the fused
      partitioning peptides. In the phase system with the largest effects, the
      partition coefficient was enhanced from 1.6 to 11.6 by fusing one tetrapeptide
      sequence to the 147 amino acid model ZZ protein. By the fusion of three
      partitioning peptides, the coefficient was increased to 96.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1367660
TI  - Real time automated simultaneous double-stranded DNA sequencing using two-color
      fluorophore labeling.
AB  - We determined the base sequences of both strands of duplex DNA simultaneously
      with an automated DNA sequencer. Primers for each strand were labeled with two
      different dyes and chain extension reactions for both strands produced four DNA
      families: "A", "C", "G", and "T". An image splitting-prism and band-pass filters
      were mounted on a real time DNA sequencer to detect fluorescences from the two
      different dyes separately. As a result, one thousand bases of a clone could be
      determined at the same time.

PMID- 1367661
TI  - Phage vectors that allow monitoring of transcription of secondary metabolism
      genes in Streptomyces.
AB  - We describe a bacteriophage phi C31-based system that permits the transcriptional
      fusion of the convenient reporter gene xylE to chromosomally located promoters in
      Streptomyces hosts. Applicability of the system to genes for secondary metabolism
      is demonstrated in an experiment showing that transcription of genes for
      actinorhodin production in Streptomyces coelicolor A3(2) depends on a transfer
      RNA gene (bldA) for the rare UUA codon. Two other phi C31::xylE vectors are
      described that allow detection of promoter activity away from their natural
      location, either at single copy in a prophage or during lytic infections in
      plaques.

PMID- 1367662
TI  - A universal method for the direct cloning of PCR amplified nucleic acid.
AB  - We have devised a simple, universal cloning strategy that permits the direct
      ligation of PCR amplified nucleic acid to a compatible vector preparation. The
      method does not require that special restriction sites or additional sequences be
      appended onto the amplification primers, nor the use of restriction
      endonucleases, modifying enzymes, or any purification procedures. This approach
      takes advantage of the single 3' deoxyadenylate extension that Thermus aquaticus,
      Thermus flavus, and Thermococcus litoralis DNA polymerases add to the termini of
      amplified nucleic acid. A new type of plasmid was constructed that allows the
      preparation of ends containing a single complementary 3' deoxythymidylate
      extension. Cloning PCR products by this method is approximately 50 times more
      efficient than blunt-ended ligation reactions. This direct PCR ligation technique
      has been engineered in-phase with a truncated lacZ gene to facilitate the
      discrimination of recombinants from non-recombinants. We have applied this method
      to directly clone amplified RNA and DNA from as little as 1 microliter of a PCR
      reaction, without prior modification or purification steps.

PMID- 1367663
TI  - An analysis of some batch and continuous kinetic data of specific monoclonal
      antibody production from hybridomas.
AB  - An analysis of batch and continuous kinetic data obtained from hybridoma cell
      cultures has been performed with particular reference to the existence of
      specific antibody production profiles. The results presented by several groups,
      including our own, have been studied. Our analysis suggests that different
      interpretations of the data can be made to those previously presented in the
      literature. In view of the significance of these profiles, particularly in terms
      of production strategies designed to maximise antibody production, we believe
      that more consideration needs to be given to accuracy in reporting of kinetic
      studies in the future.

PMID- 1367664
TI  - Comparison of culture methods for human-human hybridomas secreting anti-HBsAg
      human monoclonal antibodies.
AB  - Human-human hybridomas which secrete a human monoclonal antibody (h-MoAb) against
      hepatitis B virus surface antigen showed growth associated production kinetics.
      The rate of h-MoAb production rapidly decreased after cell growth was arrested in
      a perfusion culture, even if the perfusion rate was increased. A continuous
      suspended-perfusion culture, in which both culture broth and culture supernatant
      are continuously harvested and the same volume of fresh medium is continuously
      fed into the reactor, was developed to maintain continuous growing conditions
      during cultivation. In this culture system, the production of h-MoAb continued
      for more than 50 days with an average productivity of 5.0 mg/l of working
      volume/day. A semicontinuous immobilized-perfusion culture in which parts of the
      cells are repeatedly removed from the immobilized reactor was another useful
      technique for the long term cultivation of these h-h hybridomas. As an average h
      MoAb production rate, 62 mg/l of immobilized-bed volume/day was achieved for 65
      days of cultivation using a ceramic matrix reactor, and 327 mg/l/day was achieved
      over 47 days of cultivation using a hollow fiber reactor equipped with Cultureflo
      M. Thus, the antibody productivity per reactor volume per day by the
      semicontinuous immobilized-perfusion culture was much higher than that of the
      continuous perfusion culture in an agitation reactor.

PMID- 1367666
TI  - Application of statistical design of experiments to the optimization of factor
      VIII expression by CHO cells.
AB  - Selection and optimization of the concentrations of chemically defined components
      effective on recombinant factor VIII:C production by CHO cells have been
      performed with statistically designed experiments. Screening of efficient
      compounds on factor VIII expression was performed by using HADAMARD method, while
      a precise optimization of the concentrations of two components was achieved with
      the help of DOEHLERT method. Increased specific activity of factor VIII and
      reduced cost medium have been obtained with a fewer number of experiments than
      compared to a less rational approach.

PMID- 1367665
TI  - Extended expression of liver functions of hepatocytes in collagen-contained cell
      aggregates (cell packs).
AB  - The functions of hepatocytes under the collagen-contained cell aggregate (cell
      pack) conditions were studied using liver-specific protein synthesis. Freshly
      isolated murine hepatocytes were suspended in the medium containing collagen and
      centrifuged, and the resultant cell masses were cultured on the porous membranes
      floating on the medium. In these cultures cells were attached to each other three
      dimensionally with collagen present in the intercellular spaces. Cultured
      hepatocytes in the cell pack maintained high and stable activity in the
      expression of their functions for more than 2 weeks, even when cultured with the
      medium lacking any hormones and serum, whereas hepatocytes in monolayer cultures
      lost their functions within a week. Similarly, when the cell packs of rat
      hepatocytes were transplanted into rat spleens, they could retain viability in
      the form of cell aggregate with the expression of liver-specific albumin mRNA at
      a higher level than in the transplanted cell suspensions. The lifespan and the
      initial expression level of hepatocellular functions in culture were similar to
      that of the cell pack in cell aggregates without collagen and in cellular
      monolayers on the collagen gel respectively. It was concluded that the condition
      where cells are in contact with each other has an important role in the
      expression of hepatocellular functions and collagen present in the intercellular
      spaces enhances the functional levels.

PMID- 1367667
TI  - Erythropoietic progenitor cells from premature neonates studied using a validated
      serum-deprived medium. Evidence that peripheral blood BFU-E from premature
      neonates are increased in number and are highly dependent upon burst promoting
      activity for in vitro growth.
AB  - We have examined a serum-deprived culture system in order to verify that it is
      suitable for the study of burst forming unit erythroid (BFU-E) progenitor cells
      from premature neonates. Optimum growth of BFU-E from premature neonates was
      observed with each media constituent using the same concentration as that
      previously described for adult subjects. Growth of immature BFU-E from premature
      neonates were highly dependent upon a source of Burst Promoting Activity and
      mature BFU-E derived colonies emerged at day 12 compared to day 14 in adults. Our
      preliminary results with the validated medium suggest that premature infants have
      increased peripheral blood concentrations of BFU-E compared to healthy adult
      controls.

PMID- 1367668
TI  - Protein engineering.

PMID- 1367669
TI  - Structure prediction and modelling.
AB  - Protein structure prediction from sequence remains a major goal in molecular
      biology. The methods described in this review concentrate on deriving structural
      information through the detection of similarities between a test sequence and a
      database of known structures. Such methods are often referred to as knowledge
      based strategies reflecting the use of a structural database in the analyses. The
      past year has seen considerable advances in both the development of automated
      procedures and their application to protein sequences of outstanding biological
      interest.

PMID- 1367670
TI  - New nuclear magnetic resonance structures and structural methodology.
AB  - Progress in the field of protein nuclear magnetic resonance spectroscopy during
      the past year has included the elucidation of a number of new structures. In
      addition, several critical developments in the experimental methodology have
      opened up the potential for applying the nuclear magnetic resonance-based
      approach to structure determination in solution of recombinant proteins in excess
      of 15 kD.

PMID- 1367671
TI  - New molecular biology methods for protein engineering.
AB  - This review outlines recent advances in the application of molecular biological
      techniques to the study of protein structure and function. The chapter is divided
      into four main sections: methods for oligonucleotide-directed mutagenesis;
      mutational strategies for identifying functional residues and domains; systems
      for expression; and future developments. Few new methods were reported in 1990;
      however, a number of the papers that appeared represent refinements of previously
      reported strategies. This review is also published in Current Opinion in
      Structural Biology 1991, 1:605-610.

PMID- 1367673
TI  - Chemical methods of protein synthesis and modification.
AB  - Chemical and recombinant methods have continued to complement one another in the
      synthesis of protein analogues. Chemical methods remain particularly valuable
      when non-coded modifications are to be introduced, although it has been accepted
      since the commercialization of semisynthetic human insulin that they can also be
      used effectively for coded changes, in certain cases. The main objective of all
      such operations is not methodological, but is the production of molecules for
      practical use and further study. This goal has been reached frequently by
      chemical means during the past year.

PMID- 1367672
TI  - Routes to active proteins from transformed microorganisms.
AB  - Over-expression of recombinant proteins in microbial hosts results in the
      formation of active soluble protein or of insoluble aggregates (inclusion
      bodies). Efficient in vitro refolding strategies have been developed to
      reactivate inactive proteins from inclusion bodies. Co-expression of molecular
      chaperones may provide a tool to promote correct structure formation of
      recombinant proteins in vivo.

PMID- 1367674
TI  - Protein design.
AB  - Several noteworthy papers have been published in the past year in which the
      creation of interesting novel proteins, either by de novo design or the redesign
      of existing proteins, has been reported. Highlights include the successful design
      of proteins for binding specific ligands.

PMID- 1367675
TI  - Analysis and modulation of protein stability.
AB  - Numerous site-directed mutagenesis experiments have provided new insights into
      the stabilizing role of the individual forces and interactions within a globular
      protein molecule. Some useful guidelines and procedures are now available for
      producing genetically more stable proteins. Examples are the introduction of
      disulfide bonds, ion-binding sites, salt bridges, hydrophobic residues or
      hydrogen bonds, and the improvement of hydrophobic packing or alpha-helix
      propensity. Moreover, it is now clearly recognized that thermophilic (and, in
      general, extremophilic) bacteria produce highly stable proteins and enzymes of
      practical interest.

PMID- 1367676
TI  - Alteration of enzyme specificity and catalysis by protein engineering.
AB  - New substrate specificities can be introduced into existing enzymes for the
      purpose of making them more suitable for the chemoenzymic synthesis of single
      compound drugs and other chiral compounds. The most productive route used in the
      past year has involved the utilization of the catalytic and substrate-binding
      properties from homologous enzymes found in nature, one example being the
      broadening of the substrate specificity of yeast alcohol dehydrogenase. Other
      highlights include the creation of thermostable dehydrogenases that will
      interconvert NADPH and NADH, and the design of mutant enzymes with improved
      catalytic rates compared with their wild-type counterparts.

PMID- 1367677
TI  - Protein-protein interactions: structural motifs and molecular recognition.
AB  - The past year has brought new insights into common structural motifs used for
      protein-protein interactions by DNA-binding proteins. In addition, there have
      been significant advances in our understanding of antibody-protein complexes.

PMID- 1367678
TI  - Deletions, fusions and domain rearrangements.
AB  - The techniques of protein engineering are proving to be powerful analytical tools
      for the study of the structure and function of complex multidomain proteins. In
      particular, the overexpression of individual functional modules is providing
      proteins for three-dimensional structural analyses. Progress is also being made
      in the design and construction of novel multidomain proteins with potential
      therapeutic applications.

PMID- 1367679
TI  - Metal-binding sites in proteins.
AB  - A dramatic increase in the number of solved metalloprotein structures and recent
      breakthroughs in structural analysis have provided a sufficiently detailed
      understanding of the structural chemistry of some metal-binding sites to allow
      successful design. As a result, metal-binding site design is now one of the most
      powerful and promising approaches for influencing protein folding, assembly,
      stability and catalysis.

PMID- 1367680
TI  - Brave new proteins: what evolution reveals about protein structure.
AB  - Synthetic proteins provide important information about the principles of protein
      structure. They illuminate the processes of natural protein evaluation, but are
      not limited by these processes. Here, we review studies of several mutant
      proteins and discuss the general principles that can be derived from them.

PMID- 1367681
TI  - Engineering of proteases and protease inhibition.
AB  - Proteases are unquestionably the single most studied class of enzymes and yet
      many questions still remain about their mechanisms and roles. Protein engineering
      offers the opportunity to provide some of the answers. In this review, recent
      advances towards the understanding of stability, mechanism, specificity and
      regulation of proteases and their inhibitors are outlined. In addition, the
      application of this increased understanding is also discussed.

PMID- 1367683
TI  - Protein engineering.

PMID- 1367682
TI  - CD4: its structure, role in immune function and AIDS pathogenesis, and potential
      as a pharmacological target.
AB  - CD4 is critical for the development and function of the CD4+ subset of T cells
      and also subserves as the receptor for the human immunodeficiency viruses.
      Reports in the past year clarify the role and the molecular interactions of CD4
      in these events. Determination of the structure of an extracellular fragment of
      CD4 reveals novel variations of the immunoglobulin fold and provides an atomic
      framework for interpretation of its interactions with MHC class II molecules and
      with gp120, the external envelope glycoprotein of the human immunodeficiency
      virus.

PMID- 1367684
TI  - Effect of culture process on alkaloid production by Catharanthus roseus cells. I.
      Suspension cultures.
AB  - The processes for production of indole alkaloids in shake flask suspension
      cultures of Catharanthus roseus cells using Zenk's alkaloid production medium
      (APM) were evaluated. The 1-stage process consisted of inoculating APM and
      incubating for 15 days. The 2-stage process involved 6 d of cultivation in growth
      medium followed by 15 d of incubation in APM. Growth, main nutrient consumption
      and alkaloid production were monitored. Both culture processes produced
      approximately 20 g dw per 1 biomass. However, 2-stage cultures yielded an
      inorganic nutrient richer and more active plant cell biomass, richer in inorganic
      nutrients, as indicated by higher (greater than 70%) nutrient availability and
      consumption. Total and individual indole alkaloid production were 10 times higher
      (740 mg l-1 and 25 to 4000 micrograms per g dw, respectively) for 2-stage than
      for 1-stage cultures. For both processes, highest alkaloid productivity coincided
      with complete extracellular consumption of major inorganic nutrients, especially
      nitrate, by the cells. Complete carbohydrate consumption in 2-stage cultures
      resulted in a 40% decline in production. Small but significant (approximately
      10%) product release was observed for both culture regimes, which seemed not to
      be related to cell lysis.

PMID- 1367685
TI  - Production of hepatitis B surface antigen (preS2 + S) by high-cell density
      cultivations of a recombinant yeast.
AB  - A high-cell density bioprocess has been developed for the production of hepatitis
      B surface protein (preS2 + S) by recombinant yeast. This fed-batch process
      utilizes a growth medium containing yeast extract, soy peptone and glucose which
      was fed at a constant rate to maintain cells in a respiratory state. Cell
      densities of up to 60 g l-1 dry weight were achieved, which represented a 6-fold
      increase over those from batch bioprocesses. This increase in cell mass was
      attained without compromising specific activity; therefore, volumetric
      productivities of six times those of batch bioprocesses were achieved.

PMID- 1367686
TI  - Large scale expression and purification of recombinant HIV-1 proteinase from
      Escherichia coli.
AB  - The availability of target proteins in sufficient quantity is a limiting factor
      in crystallographic studies and therefore in rational drug design. Even after
      optimisation, expression of recombinant proteins may be low and the only way to
      produce enough protein is by large scale cell growth/purification. HIV-1
      proteinase in Escherichia coli, which due to its toxicity is expressed as a
      soluble protein only at around 0.1% of total protein, is a paradigm for this. In
      this paper a detailed process for large scale expression and purification of HIV
      1 proteinase which delivers material of suitable quantity (30 mg from 500 g of
      wet weight of cells) and quality for crystallographic studies is described.

PMID- 1367687
TI  - The 1,4-beta-D-glucan glucanohydrolases from Phanerochaete chrysosporium. Re
      assessment of their significance in cellulose degradation mechanisms.
AB  - A physico-chemical, functional and structural characterization, including partial
      sequence data, of three major 1,4-beta-D-glucan glucanohydrolases (EC. 3.2.1.4)
      isolated from the culture filtrate of the white-rot fungus Phanerochaete
      chrysosporium, shows that all three enzymes belong to a single family of
      cellulases. EG44, pI 4.3, (named after its apparent molecular mass in kDa), shows
      a clear homology with Schizopyllum commune Endoglucanase I (EGI); whereas EG38,
      pI 4.9, (named in the same manner) is related more closely to Trichoderma reesei
      (Trichoderma longibrachiatum) Endoglucanase III (EGIII). EG36, pI 5.6-5.7, is
      probably an EG38 protein lacking its cellulose binding domain. Strong synergistic
      action is induced by the enzymes acting in concert with cellobiohydrolases (CBHI
      and CBHII) from the same organism, indicating a highly effective enzymatic system
      for cellulose degradation. Controlled proteolysis with papain has allowed a so
      far unique cleavage of endoglucanases EG44 and EG38 into two domains: a core
      protein, which virtually lacks the capacity to absorb onto microcrystal-line
      cellulose but retains full catalytic activity against carboxymethyl cellulose and
      low molecular weight soluble substrates; and a peptide fragment corresponding to
      the cellulose binding domain. The latter appears to be of paramount significance
      in the mechanisms involved in the hydrolysis of microcrystalline cellulose.

PMID- 1367688
TI  - Enzyme sensor-FIA-system for on-line monitoring of glucose, lactate and glutamine
      in animal cell cultures.
AB  - Enzyme sensors for glucose, lactate and glutamine were connected via flow
      injection analysis (FIA) devices to two different bioprocesses. They were used
      for on-line process control of perfused bioreactor systems containing mammalian
      cell lines producing a monoclonal antibody and recombinant interleukin-2. The
      biosensor system gives direct access to important process data which can be used
      as control parameters for long term cell cultivation systems.

PMID- 1367689
TI  - Effect of culture process on alkaloid production by Catharanthus roseus cells.
      II. Immobilized cultures.
AB  - Two processes for the production of indole alkaloids 2 l surface-immobilized
      bioreactor cultures of Catharanthus roseus cells using Zenk's Alkaloid Production
      Medium (APM) were evaluated. The 1-stage process consisted of inoculating APM
      containing bioreactors and incubating for 15 d. The 2-stage process involved
      inoculating growth medium-containing bioreactors, growing the immobilized
      cultures for a certain period of time and subsequently replacing this medium with
      APM. The production stage which lasted for 15 d. High production in 2-stage
      cultures required the replacement of the growth regulator 2,4
      dichlorophenoxyacetic acid by indole-3-acetic acid in the growth medium and a
      growth stage of 6 d (late exponential phase) before production initiation.
      Growth, main nutrient consumption and alkaloid production were monitored. Both
      culture regimes resulted in similar biomass production, dw (10-13 g l-1). The 2
      stage cultures yielded biomass richer in organic nutrients (200-300%) and with
      higher respiratory activity (approximately 250%), indicated by their lower
      biomass-to-carbohydrate yields (31% and 26%), as compared to 1-stage cultures
      (41%). Two-stage cultures produced more known products (10 as compared to 6) at
      yields (5 to 4800 micrograms g-1) 3 to 5 times higher than 1-stage cultures. More
      alkaloids were alkaloids released in the medium of 2-stage cultures, under non
      lysing conditions, (20 to 4700 micrograms l-1) than in 1-stage cultures (20 to
      460 micrograms l-1). These results were compared to those obtained from shake
      flask cultures performed at the same time, with the same C. roseus cell line and
      under similar regimes and reported previously. Suspension and immobilized
      cultures performed according to the 1-stage regime showed similar total
      production. However, release of known alkaloids was 2 to 3 times higher in
      immobilized than in suspension cultures. Total alkaloid production of 2-stage
      suspension cultures was 3.8-fold higher than 2-stage immobilized cultures. Two
      stage immobilized cultures released 4 more known alkaloids than the 2-stage
      suspensions. Lower oxygen availability in the 2 l immobilized cultures may
      explain lower specific growth rates (0.15-0.22 d-1) and total alkaloid production
      levels, compared to 200 ml suspension cultures (0.2-0.4 d-1) reported in our
      previous paper.

PMID- 1367690
TI  - Stimulated indole alkaloid release from Catharanthus roseus immobilized cultures.
      Initial studies.
AB  - Vacuolar sequestration of valuable secondary metabolites remains the major
      limitation to the use of immobilization technology for large scale plant-cell
      based bioprocesses, which otherwise may be a more efficient culture system than
      suspension for this biomass. In this initial study, the release of indole
      alkaloids produced by immobilized Catharanthus roseus cells cultured in Zenk's
      Alkaloid Production Medium was evaluated. Unstimulated alkaloid release in
      immobilized cultures reached levels of 10 to 50% of total production or 3 to 100%
      of known alkaloid content (30 to 4700 micrograms l-1), which was higher than that
      found for suspension cultures of the cell line used (10 to 25% of total
      production) without apparent cell lysis. Modifications of the medium pH value of
      immobilized cultures were explored in order to improve this release. Periodical
      additions of acid (HCl 0.1 N) or base (KOH 0.1 N) solutions (2% v/v) to different
      cultures resulted in rapid (less than 3 h) and transient variations in
      extracellular pH value from 5.5 to 4.3, and 5.8 to 8.5, respectively. In both
      cases, these variations provoked significant increase in total alkaloid (from
      approximately 5-10 mg l-1 to 15 mg l-1), ajmalicine (from 0 to approximately 0.29
      mg l-1) and serpentine (from 0 to approximately 0.20 mg l-1) release, without
      apparent cell lysis or decrease in the culture viability. This product release
      was estimated to represent 100% of alkaloids produced.

PMID- 1367691
TI  - Dynamics of activation of a galactose-inducible promoter in Saccharomyces
      cerevisiae.
AB  - We have investigated the dynamics of accumulation of the Escherichia coli beta
      galactosidase (beta-gal) under the control of a promoter containing the galactose
      inducible upstream activating sequence (UASG) in single Saccharomyces cerevisiae
      cells. The accumulation of beta-gal in single cells following the addition of the
      inducer, galactose, was determined using an in situ combined DNA and
      immunofluorescent stain in conjunction with flow cytometry. Two strains were
      studied, D603/2i, which has two copies of the galactose-inducible fusion gene
      integrated into its genome, and D603/pLGSD5, which carries a 2 microns-based
      plasmid containing the fusion gene. Flow cytometry results indicate that
      accumulation of beta-gal within the first three hours following the addition of
      galactose is dependent on cell cycle position. Two proposed mechanisms explaining
      this observed behavior are (1) the cell-cycle-dependent synthesis of the fusion
      protein or (2) the unequal partitioning of the protein at cell division between
      mother and daughter cells.

PMID- 1367692
TI  - Production of homogeneous basic fibroblast growth factor by specific enzymatic
      hydrolysis of larger microheterogeneous molecular forms.
AB  - The 146-amino acid form of basic fibroblast growth factor (bFGF) was expressed in
      Escherichia coli and purified by a two step process including ion exchange and
      heparin-Sepharose chromatographies. However, the resulting protein consisted of a
      mixture of 146- and 145-amino acid forms, indicating that, besides the initial
      methionine, also the following residue (proline) was removed from the N-terminus.
      The same phenomenon was observed when the 155-amino acid form, which is
      biologically equivalent to the shorter one, was expressed in E. coli. Taking into
      account the previously known data concerning the possible mechanism of cleavage
      of the extended forms of bFGF in vivo, we developed an efficient enzymatic
      process that allows the production of an homogeneous 146-amino acid form from
      recombinant NH2-end extended forms. This process takes advantage of the
      protecting effect that heparin exerts on bFGF. Accordingly, when bFGF, complexed
      to heparin, is treated with pepsin A, an aspartic protease with a broad
      specificity, only the Leu9-Pro10 peptide bond is cleaved generating the 146-amino
      acid form. Quantitative yields of this reaction are also achieved when bFGF is
      bound to a heparin-Sepharose column, allowing the integration of this enzymatic
      step directly during purification of the recombinant extended forms of bFGF.

PMID- 1367693
TI  - Dye-promoted precipitation of serum proteins. Mechanism and application.
AB  - Immobilized dyes have been used primarily for purification of nucleotide
      dependent enzymes and proteins from plasma and other sources. Due to their low
      costs, high protein binding capacity and resistance to degradation dyes bear the
      potential as ligand for affinity separation of proteins on a large scale. In this
      paper dyes have been used for precipitation of proteins. Using albumin,
      prealbumin, alpha 1-acid glycoprotein and immunoglobulin G as model proteins we
      could demonstrate that dye-promoted precipitation depends on several factors
      which include the structure of the dye, the pH of the solution, the dye/protein
      molar ratio and the intrinsic properties of the proteins. It revealed that most
      of the dyes tested were endowed with the precipitating potential. The efficacy of
      precipitation was found to increase with the complexity of the dye structure.
      However, the amount of a dye required for total precipitation was found to be
      different for a given protein. Electrostatic as well as hydrophobic forces are
      involved in the mechanism of precipitation. It was demonstrated that by
      optimizing the conditions, mixtures of proteins can be resolved by dye-promoted
      precipitation. The high sensitivity of the reaction offers the possibility of
      using this method for rapid concentration of very diluted protein solutions.

PMID- 1367695
TI  - Neural network programming in bioprocess variable estimation and state
      prediction.
AB  - A neural network program with efficient learning ability for bioprocess variable
      estimation and state prediction was developed. A 3 layer, feed-forward neural
      network architecture was used, and the program was written in Quick C ver 2.5 for
      an IBM compatible computer with a 80486/33 MHz processor. A back propagation
      training algorithm was used based on learning by pattern and momentum in a
      combination as used to adjust the connection of weights of the neurons in
      adjacent layers. The delta rule was applied in a gradient descent search
      technique to minimize a cost function equal to the mean square difference between
      the target and the network output. A non-linear, sigmoidal logistic transfer
      function was used in squashing the weighted sum of the inputs of each neuron to a
      limited range output. A good neural network prediction model was obtained by
      training with a sequence of past time course data of a typical bioprocess. The
      well trained neural network estimated accurately and rapidly the state variables
      with or without noise even under varying process dynamics.

PMID- 1367694
TI  - On-line monitoring of marine cyanobacterial cultivation based on phycocyanin
      fluorescence.
AB  - A novel on-line fluorescence monitoring system for marine cyanobacterial
      cultivation was developed. This method is based on the measurement of
      intracellular phycocyanin content, which is the major light harvesting protein. A
      fluorescence spectrophotometer, equipped with a flow cell connected with a
      culture liquid recycling tube was used. Experiments were carried out using a
      marine unicellular cyanobacteria Synechococcus sp. NKBG 042902 isolated from
      Japanese coastal sea water. We have optimized excitation wavelength to avoid the
      light scattering, using non-pigmented old cells which no longer contained
      phycocyanin. At an excitation wavelength of 590 nm, light scattering was
      minimized. Viable cell concentration could be measured in the range of 2 x 10(6)
      to 2 x 10(8) cells per ml, without pronounced light scattering. Continuous
      monitoring of marine cyanobacteria cultivation was performed. Cell concentrations
      were determined by both culture fluorescence and by using a hemacytometer. A good
      linear correlation was obtained. We conclude that on-line monitoring of
      cyanobacterial culture fluorescence based on phycocyanin is a rapid, efficient
      and also versatile method for determining viable cell concentration.

PMID- 1367696
TI  - Transcription of eukaryotic genes with impaired internal promoters: the use of a
      yeast tRNA gene as promoter.

PMID- 1367697
TI  - Increased antigen binding strengths of hybrid antibodies produced by human hybrid
      hybridomas.
AB  - Two cell lines of human hybridomas were fused to generate hybrid antibodies. One
      human hybridoma cell line was HT2 producing IgM monoclonal antibody (MAb)
      reactive to carboxy peptidase A (Cpase) and double stranded DNA (ds DNA) and
      another was SU-1-D2 secreting IgM MAb reactive to ds DNA but not to Cpase. Most
      hybrid hybridomas obtained by fusion of the two hybridomas secreted hybrid
      antibodies exhibiting increased antigen binding strengths. All of the hybrid
      antibodies with increased binding strengths against Cpase and ds DNA contained
      only the light chains derived from SU-1-D2. These results suggested that increase
      in the binding strength of the hybrid antibodies resulted from heterogeneous
      association of H and L chains derived from HT2 and SU-1-D2 cells.

PMID- 1367698
TI  - Growth limitation in hybridoma cell cultures: the role of inhibitory or toxic
      metabolites.
AB  - Hybridoma cells usually grow to fairly low cell densities in batch cultures (1-3
      x 10(6) cells/ml). The reason for this is either that essential nutritional
      components of the medium are consumed, or that the cells produce some kind of
      inhibitory or toxic metabolite. This investigation presents evidence for the
      latter. Spent medium from cultures of hybridoma cells did not support growth of
      cells at lower cell densities (1-3 x 10(5) cells/ml). The ability to support cell
      growth could not be restored by adding additional serum, energy sources (glucose,
      pyruvate) or L-glutamine. Furthermore, the consumption of amino acids could not
      account for this growth inhibition. On the contrary, the spent medium contained a
      substance that inhibited cell growth. This substance or metabolite was found in a
      fraction eluted from a gel filtration column when spent medium was applied to the
      column. This substance was found in the spent medium from all hybridoma and
      myeloma cell lines that were tested. The molecular weight of the substance was
      about 5 kD. Spent medium from two hybridoma cell lines also contained a substance
      that was eluted in the same fraction as albumin (67 kD). It is likely that this
      (or these) substance(s) is responsible for the growth limitation in hybridoma
      cell cultures.

PMID- 1367699
TI  - Hybridoma growth and monoclonal antibody production in iron-rich protein-free
      medium: effect of nutrient concentration.
AB  - The iron-rich (500 microM ferric citrate) protein-free supplement was added to
      six different basal media. Cell growth and monoclonal antibody production of a
      mouse-mouse hybridoma were investigated in 1.3 1 batch cultures performed in a
      laboratory bioreactor with automatic control of pH and dissolved oxygen
      concentration. RPMI 1640 served as the control medium. Fortification of the basal
      medium by balanced mixtures of amino acids and vitamins showed higher positive
      effect than daily supplementation by glucose and glutamine. Strongly fortified
      medium, based on RPMI 1640, was found superior to other basal media. The
      viability index increased by a factor of 3.04 and the total antibody production
      by a factor of 2.82, relative to the control.

PMID- 1367700
TI  - A modification of tooth germ cultivation in vitro and in ovo.
AB  - Mandibular molar anlages excised from 17-day mouse foetuses were cultured in
      vitro or in ovo (on the chorioallantoic membrane). In both cases, the explants
      were underlain either with a Millipore filter or with a piece of fibrin foam.
      Tooth germs were harvested after 7 days of cultivation and processed
      histologically. Spatial arrangement was highly preserved in the tooth germs
      cultured in vitro on fibrin foam. In vitro cultures on Millipore filters revealed
      significant flattening of tooth germs, caused especially by the collapse of
      enamel organ and the pulp. The cytodifferentiation of tooth germs cultured in
      vitro on both substrates (Millipore filter, fibrin foam) was characterized by the
      presence of odontoblasts, polarizing ameloblasts and predentine. The
      cytodifferentiation of tooth germs cultured in ovo on Millipore filters placed on
      chorioallantoic membrane was characterized by the presence of odontoblasts,
      ameloblasts, predentine, dentine and enamel. However, the flattening of these
      explants was identical with the changes of the explants cultured on Millipore
      filters in vitro. In ovo cultivation on the fibrin foam failed to bring
      satisfactory results.

PMID- 1367702
TI  - Biotechnology in India.

PMID- 1367701
TI  - An improved method for chromosome banding after fluorescence in situ
      hybridization: use of a tetramethylrhodhamine-conjugated BrdU antibody.
AB  - A method for high quality chromosome banding after in situ hybridization with
      biotinylated probes has been developed. Fluoresceine-conjugated avidin is used
      for probe detection, while chromosome banding is performed with a
      tetramethylrodhamine-conjugated anti-BrdU antibody. In this way probe
      localization and chromosome identification can be performed simultaneously simply
      by changing the incidental light wavelength.

PMID- 1367703
TI  - The future of drug evaluation in Australia Review of the Baume Report, a question
      of balance.

PMID- 1367705
TI  - Analytical biotechnology.

PMID- 1367704
TI  - Immunoassay.

PMID- 1367706
TI  - Enzyme assays.
AB  - The past year or so has seen the development of new enzyme assays, as well as the
      improvement of existing ones. Assays are becoming more rapid and sensitive as a
      result of modifications such as amplification of the enzyme product(s).
      Recombinant DNA technology is now being recognized as a particularly useful tool
      in the search for improved assay systems.

PMID- 1367707
TI  - Biosensors.

PMID- 1367708
TI  - Affinity chromatography for protein isolation.
AB  - Thousands of reports concerning protein purification have appeared in the past
      year, and over 150 of these involved, at least in part, the affinity
      chromatography process. Immobilized membrane affinity chromatography, temperature
      programmed elution, and centrifugal affinity chromatography are among the most
      significant new techniques amid the myriads of applications in this mature field.

PMID- 1367709
TI  - Perspectives on immobilized proteins.

PMID- 1367710
TI  - Structural analysis of proteins by laser desorption and electrospray mass
      spectrometry.
AB  - The development of electrospray and matrix-assisted laser desorption mass
      spectrometry has provided protein chemists with tools for peptide and protein
      structure analysis with unprecedented sensitivity and molecular weight range. The
      two technologies can be viewed as competitive with respect to their molecular
      mass determinations, but complementary with respect to their differences in
      instrumentation, sample preparation methods, and nature of spectra produced.

PMID- 1367711
TI  - Polymerase chain reaction techniques.

PMID- 1367712
TI  - Gene probes.
AB  - Gene probes are used in virtually all disciplines of the life sciences. Probes
      will probably have their greatest impact in health care when used as diagnostic
      tools to detect and identify micro-organisms responsible for infectious disease.
      This review will use development of gene probes for the clinical laboratory as a
      theme and review recent patents and publications which have nurtured probe
      development.

PMID- 1367713
TI  - Separation and analysis of DNA by electrophoresis.
AB  - Pulsed-field gel electrophoresis, the polymerase chain reaction and capillary
      electrophoresis represent major technical advances in DNA electrophoresis in the
      last few years. This has lead to a number of new applications, including the
      cloning of large DNA fragments, multiplex analysis of DNA samples, and the
      detection of single base changes in DNA. New fluorescent and chemiluminescent
      techniques promise to simplify detection methods.

PMID- 1367714
TI  - Flow injection analysis with immobilized reagents.
AB  - Immobilized reagent phase flow injection analysis can be configured as discrete
      reagent cells upstream of the sensor element or as an integral
      reagent/transduction system (flow injection analysis-biosensor). The former
      approach has attracted greater attention because several assays can be assembled
      with greater versatility in reagent column units employing a single sensor, than
      can be co-immobilized on the surface of a transducer.

PMID- 1367715
TI  - Large-scale DNA sequencing.

PMID- 1367716
TI  - Streptomyces: a host for heterologous gene expression.
AB  - Streptomyces species offer many potential advantages as hosts for the expression
      and secretion of eukaryotic gene products. In this review we discuss the
      expression and localization signals that have been used to direct heterologous
      gene expression and the applications of these signals. Finally, we discuss future
      strategies aimed at increasing the capacity of this host for the high level
      production of biologically active eukaryotic gene products.

PMID- 1367717
TI  - Proteolytic activities in Bacillus.
AB  - Major advances have been made in understanding the regulation of expression of
      Bacillus subtilis protease genes. A phosphorelay mechanism as well as a two
      component regulatory system allow conditions of the growth medium to be
      transmitted to the gene level resulting in expression of extracellular protease
      genes.

PMID- 1367718
TI  - Gene expression in yeast: protein secretion.
AB  - Maximizing efficiency for the secretion of proteins from yeast requires an
      understanding of the rate limiting stages in secretion that can result from high
      levels of gene expression. Recent progress in this area has produced a number of
      improvements in yeast expression systems for protein secretion.

PMID- 1367720
TI  - Gene expression using Xenopus oocytes.
AB  - Xenopus oocytes have been used as a surrogate genetic system for the study of
      many facets of gene expression. Some recent salient examples where injected
      oocytes proved to be indispensable for the analysis of transcription,
      translation, RNA/protein transport, and ion channel formation are described.

PMID- 1367719
TI  - Gene expression systems for filamentous fungi.
AB  - The extraordinary capacity of filamentous fungi to produce large quantities of
      extracellular protein, together with the advent of DNA-mediated fungal
      transformation, has resulted in rapid advances in the development of gene
      expression systems for filamentous fungi. This review focuses on recent
      developments in the expression of both fungal and non-fungal genes and
      improvements to the host.

PMID- 1367721
TI  - Recombinant gene expression in cultured Drosophila melanogaster cells.
AB  - Cultured Drosophila Schneider line 2 cells provide a versatile and efficient
      system for the expression of recombinant gene products that retain authentic
      properties. An efficient method now exists for the expression of large amounts of
      recombinant protein from continuous cell lines. In addition, Schneider line 2
      cells have proven reliable as a background for in vivo studies of gene regulation
      and protein function.

PMID- 1367722
TI  - Retrovirus-mediated gene expression in mammalian cells.
AB  - Significant advances have been made in precisely defining the elements in the
      Moloney murine leukemia virus genome responsible for tissue-restricted
      expression. This knowledge should lead to improved expression vectors for gene
      transfer in mammalian cells. In the past year, retrovirus-mediated gene
      expression in a diverse range of cell types has been reported. These cells have
      been used to study gene transfer relevant to a range of inherited diseases.

PMID- 1367723
TI  - Vaccinia virus vectors for gene expression.
AB  - Improvements to vaccinia virus expression vectors continue to be made. In
      particular, there are new methods for the construction of recombinant viruses,
      ways of increasing the level of gene expression, and vectors that allow the
      inducible expression of selected genes.

PMID- 1367724
TI  - Adenovirus vectors for gene expression.
AB  - Adenoviruses possess a combination of features that make them highly suitable as
      vectors for expression of heterologous genes. Non-conditional and non-defective
      adeno-vectors have been constructed to obtain high level expression of a number
      of foreign genes and some of them have been shown in animal models to exhibit
      excellent promise as vaccine candidates.

PMID- 1367725
TI  - Gene amplification in mammalian cells: strategies for protein production.
AB  - Gene amplification is an experimental strategy for increasing protein production
      in mammalian cells. Co-amplification of the target gene by genetically linking it
      to one or more selectable and amplifiable genetic markers is a particularly
      successful strategy. A number of papers published in the past year or two
      illustrate the use of gene amplification to achieve high levels of expression.

PMID- 1367726
TI  - Mammalian cell gene expression: protein glycosylation.
AB  - Considerable advances have been made in identifying the factors determining the
      glycosylation pattern of glycoproteins secreted by mammalian cells. This has
      allowed a greater appreciation of the way in which recombinant proteins may be
      glycosylated after expression in a heterologous system. The studies reviewed
      herein extend the wider view that glycosylation of native and recombinant
      proteins is a complex event dependent on the protein moiety, the host cell, and
      also the environment in which transfected cells are cultured. The details of the
      way in which these factors combine to establish the glycosylation pattern of a
      secreted protein are now beginning to be unravelled.

PMID- 1367727
TI  - Expression cloning systems.
AB  - This review will cover the use of expression cloning in Xenopus oocytes, fission
      yeast, and mammalian cells. Of the systems covered herein, transient expression
      cloning systems in Xenopus oocytes and mammalian cells have proven to be the most
      effective and versatile, as demonstrated by the large number of cDNA clones
      isolated by these two methods in the past year. Of particular interest, are
      recent advances in the screening methodologies used in conjunction with transient
      expression in mammalian cells which have permitted the application of this system
      in the isolation of cDNAs encoding intracellular proteins.

PMID- 1367728
TI  - Gene expression in yeast: Pichia pastoris.
AB  - Recent studies have shown the versatility and utility of the Pichia pastoris
      expression system. Improvements in strains have boosted the yield of proteins and
      peptides to the commercially feasible range. The Pichia pastoris expression
      system will soon be used to manufacture proteins for human clinical trials.

PMID- 1367729
TI  - Optimizing protein folding to the native state in bacteria.
AB  - A correctly folded protein is usually both active and soluble. This review
      focuses on novel ways to improve the folding of recombinant proteins during
      production in bacteria and includes a few tips for refolding proteins. Major
      results in correlating protein primary structure with proper folding and
      stability, and the production of viral antigens and antibodies in bacteria are
      also discussed.

PMID- 1367730
TI  - Expression systems.

PMID- 1367731
TI  - Development of a turbidimetric immunoassay for on-line monitoring of proteins in
      cultivation processes.
AB  - An on-line assay for a thermostable pullulanase and antithrombin III (AT III) is
      described. The assay is based on the formation of aggregates between the protein
      to be measured and antibodies raised against this protein. Assay automation was
      achieved by utilizing the flow injection analysis (FIA) principles. The
      apparatus, a stopped-flow, merging-zone manifold, is described in detail. Since
      the reaction used in an FIA system does not have to reach equilibrium, it was
      possible to reduce the time for an assay cycle to 2.5 min. A method for
      simulating cultivation conditions was developed for assay optimization. Using
      this method, a detection limit of 1 mg l-1 together with a standard deviation of
      1.5 was found. A sandwich ELISA was used as reference assay in the case of AT III
      and an enzymatic activity assay in the case of pullulanase. Correlation
      coefficients of 0.988 (AT III) and 0.976 (pullulanase) were determined. The
      turbidimetric assay was successfully used for pullulanase monitoring during a 240
      h cultivation of Clostridium thermosulfurogenes.

PMID- 1367733
TI  - The development of a malaria vaccine.
AB  - This paper is a progress report and summarises R & D by the consortium to develop
      a malaria vaccine. The research strategies and research progress are discussed.
      The business arrangements and the roles of each partner are given.

PMID- 1367732
TI  - Leukaemia inhibitory factor: multiple biological actions and commercial
      potential.

PMID- 1367734
TI  - The use of peptides as therapeutics & vaccines.

PMID- 1367735
TI  - Vaccine R & D at CSIRO's Division of Tropical Animal Production.
AB  - The extensive research on animal vaccines being undertaken by the CSIRO Division
      of Tropical Animal Production in Brisbane is summarised in this paper. Much of
      the research is being developed in conjunction with commercial partners. Vaccines
      are being developed for the cattle tick, Babesia, Anaplasma, sheep blowfly,
      buffalo fly and bovine ephemeral fever.

PMID- 1367736
TI  - Veterinary parasite vaccines.
AB  - This paper overviews the new veterinary parasite vaccines being developed by
      Biotech Australia Pty Ltd (one of Australia's largest biotechnology companies) in
      conjunction with other Australian research organisations. The research strategy
      adopted by the company is given.

PMID- 1367737
TI  - Who's engineering biotechnology regulations?

PMID- 1367738
TI  - Magnetic applications in sphere molecular biology.

PMID- 1367739
TI  - Polymerase chain reaction (PCR) poised for multiple routine diagnostic
      applications.

PMID- 1367741
TI  - Unravelling the mysteries of molecular audit: MHC class I restriction.

PMID- 1367740
TI  - How to get confocal performance from a fluorescence microscope.

PMID- 1367743
TI  - A productive mix of cultures.

PMID- 1367742
TI  - Of mice and mimics.

PMID- 1367744
TI  - Cell-based assays--technology providing alternatives to animal testing.

PMID- 1367745
TI  - Lichen-forming fungi: potential sources of novel metabolites.
AB  - The challenge for today's pharmaceutical industry lies in the discovery and
      development of new, pharmacologically active molecules. Metabolites produced by
      microorganisms, and fungi in particular, are a resource for which the therapeutic
      potential has been recognized, but one that remains largely unexplored and
      unexploited. Approximately 20% of all known fungal species are obligate symbionts
      in lichens; this major group of fungi has been long neglected by mycologists, and
      overlooked by industry.

PMID- 1367746
TI  - Understanding and controlling detrimental bioreactor biofilms.
AB  - Unintentional biofilm formation within a bioreactor can have serious detrimental
      effects on bioreactor performance. These range from the obvious (reduced heat
      transfer efficiency, increased frictional resistances, and fouling of internal
      diagnostic probes) to the more subtle (atypical econiches, species- or strain
      specific adhesion, and inaccurate estimates of culture stoichiometric and kinetic
      parameters). Detection and control of unwanted biofilm formation in bioreactors
      are also considered.

PMID- 1367747
TI  - Fluid-mechanical damage of animal cells in bioreactors.
AB  - The fluid-mechanical and some biological aspects of damage to animal cells in
      bioreactors due to agitation and/or aeration are attracting renewed attention. In
      microcarrier bioreactors, cell damage is due to forces generated by the
      interaction of microcarrier beads with each other and also with small turbulent
      eddies. For freely suspended cells grown in mixed bioreactors, cell damage is
      most frequently due to bubble breakup or fast-draining liquid films around
      rearranging gas-liquid interfaces.

PMID- 1367748
TI  - Effect of cacao husk extract on human immunodeficiency virus infection.
AB  - A sodium hydroxide extract from cacao husk inhibited the cytopathic effect of
      human immunodeficiency virus type 1 (HIV-1) against HTLV-1-transformed T-cell
      lines MT-2 and MT-4. It also inhibited syncytium formation between HIV-infected
      and uninfected lymphoblastoid T-cell line, MOLT-4. The anti-HIV activity was
      concentrated by membrane filter fractionation to a fraction with molecular weight
      of 100-300 KDa. Anti-HIV activity of the extract was attributable to interference
      with the virus adsorption, rather than to inhibition of the virus replication
      after adsorption.

PMID- 1367750
TI  - Growth, metabolic, and antibody production kinetics of hybridoma cell culture: 2.
      Effects of serum concentration, dissolved oxygen concentration, and medium pH in
      a batch reactor.
AB  - The effects of serum, dissolved oxygen (DO) concentration, and medium pH on
      hybridoma cell physiology were examined in a controlled batch bioreactor using a
      murine hybridoma cell line (167.4G5.3). The effect of serum was also studied for
      a second murine hybridoma cell line (S3H5/gamma 2bA). Cell growth, viability,
      cell density, carbohydrate and amino acid metabolism, respiration and energy
      production rates, and antibody production rates were studied. Cell growth was
      enhanced and cell death was decreased by increasing the serum level. The growth
      rates followed a Monod-type model with serum being the limiting component.
      Specific glucose, glutamine, and oxygen uptake rates and specific lactate and
      ammonia production rates did not change with serum concentrations. Amino acid
      metabolism was slightly influenced by the serum level. Cell growth rates were not
      influenced by DO between 20% and 80% air saturation, while the specific death
      rates were lowest at 20-50% air saturation. Glucose and glutamine uptake rates
      increased at DO above 10% and below 5% air saturation. Cell growth rate was
      optimal at pH 7.2. Glucose and glutamine uptake rates, as well as lactate and
      ammonia production rates, increased above pH 7.2. Metabolic rates for glutamine
      and ammonia were also higher below pH 7.2. The consumption or production rates of
      amino acids followed the glutamine consumption very closely. Cell-specific oxygen
      uptake rate was insensitive to the levels of serum, DO, and pH. Theoretical
      calculations based on experimentally determined uptake rates indicated that the
      ATP production rates did not change significantly with serum and DO while it
      increased continually with increasing pH. The oxidative phosphorylation accounted
      for about 60% of total energy production. This contribution, however, increased
      at low pH values to 76%. The specific antibody production rate was not growth
      associated and was independent of serum and DO concentrations and medium pH above
      7.20. A 2-fold increase in specific antibody production rates was observed at pH
      values below 7.2. Higher concentrations of antibody were obtained at high serum
      levels, between 20% and 40% DO, and at pH 7.20 due to higher viable cell numbers
      obtained.

PMID- 1367749
TI  - Growth, metabolic, and antibody production kinetics of hybridoma cell culture: 1.
      Analysis of data from controlled batch reactors.
AB  - A mouse-mouse hybridoma cell line (167.4G5.3) was cultivated in a 1.5-L stirred
      tank bioreactor under constant pH and dissolved oxygen concentration. The
      transient kinetics of cell growth, metabolism, and antibody production were
      followed by biochemical and flow cytometric methods. The cell-specific kinetic
      parameters (growth and metabolic rates) as well as cell size were constant
      throughout the exponential phase. Intracellular protein and RNA content followed
      a similar trend. Cell growth stopped when the glutamine in the medium was
      depleted. Glucose could not substitute for glutamine, as glucose consumption
      ceased after glutamine depletion. Ammonia and lactate production followed closely
      glutamine and glucose consumption, respectively. Alanine, glutamate, serine, and
      glycine were produced but other amino acids were consumed. The cells are
      estimated to obtain about 45% of the total energy from glycolysis, with the
      balance of the metabolic energy provided by oxidative phosphorylation. The
      antibody was produced at a constant rate in both the exponential and decline
      phases of growth. The intracellular antibody content of the cells remained
      relatively constant during the exponential phase of growth and decreased slightly
      afterwards.

PMID- 1367751
TI  - Removal of hydrogen sulfide by Chlorobium thiosulfatophilum in immobilized-cell
      and sulfur-settling free-cell recycle reactors.
AB  - Bioconversion of hydrogen sulfide to elementary sulfur by the photosynthetic
      bacterium Chlorobium thiosulfatophilum was studied in immobilized-cell and sulfur
      settling free-cell recycle reactors. The cells immobilized in strontium alginate
      beads excreted elementary sulfur and accumulated it as crystal in the bead
      matrices, which made it possible that the reactor broth remained clear and the
      light penetrated the reactor deeper than with the free cells. In comparison with
      the free cells, the immobilized cells required 30% less light energy at a H2S
      removal rate of 2 mM/(L.h) and showed an activity of 2.4 times that of the free
      cells. However, in 40 h after the reaction the deterioration of the H2S removal
      efficiency became significant due to the accumulation of sulfur in the beads. The
      scanning electron micrograph (SEM) and energy-dispersive X-ray spectrometer (EDS)
      studies showed that the sulfur in the beads existed within a layer of 0.4 mm from
      the bead surface. In the sulfur-settling free-cell recycle reactor, about 80% of
      the sulfur excreted by the free cells could be removed in a settler. The 4-L fed
      batch reactor with the settler improved the light transmission to result in a H2S
      removal rate of 3 mumol/(mg of protein.h), 50% higher than that without it. The
      settling recycle reactor was much better in the removal of H2S than the
      immobilized-cell reactor because the former was a continuous system with the
      constant removal of sulfur particles by settling and of spent medium by supplying
      fresh medium at the same rate as the filtering rate of the reactor broth, while
      the latter was essentially a batch system where toxic metabolites and produced
      sulfur could not be removed.

PMID- 1367752
TI  - Characterization of kappa-carrageenan gels used for immobilization of Bacillus
      firmus.
AB  - In this study, aimed at a biochemical and physical characterization of kappa
      carrageenan gels used for entrapment of Bacillus firmus NRS 783 (a superior
      producer of an alkaline protease), effects of carrageenan concentration, gelation
      temperature, initial cell loading, and strength of the curing agent (KCl) on the
      properties of cell-free and cell-laden gels were examined. The physical
      properties of the differently prepared gels that were examined included density,
      free volume fraction, mechanical strength, and change in gel volume during gel
      curing. The biochemical characteristics studied included viability of gel
      entrapped cells, cell leakage from cell-laden gels, and cell penetration into
      cell-free gels. For the range of carrageenan contents investigated [between 2%
      and 5% (w/v)], the mechanical strength of the gels with/without KCl curing was
      observed to increase with an increase in carrageenan content of gels. The
      mechanical strength of each gel increased substantially upon extensive curing.
      Free volume fractions in excess of 0.8 were observed for all gels. Of cells that
      were viable prior to immobilization, 90-92% remained viable after formation and
      extensive curing of gels for cell-gel mixtures prepared at 45 degrees C. Attempts
      at prolonged storage of cell-laden gel beads at 0 degrees C as stock cultures of
      immobilized B. firmus were unsuccessful due to a significant decline in cell
      viability during such storage. On the basis of the cell leakage studies, the
      average pore sizes of 2%, 3%, 4%, and 5% gels were deduced to increase in the
      following order of carrageenan content (w/v): 4%, 3%, 2%, and 5%. Commensurate
      with the decrease in the average pore size (or the increased tightness of the
      gels) with increasing carrageenan content, both the extent of cell leakage and
      the extent of net cell penetration decreased with increasing carrageenan content
      for the first three gels. Owing to non-uniform distribution of free space and
      much larger pores, the extent of net cell penetration in 5% carrageenan gels was
      considerably low, while the extent of cell leakage in 5% carrageenan gels was an
      order of magnitude greater than the extents of cell leakage in the other three
      gels.

PMID- 1367753
TI  - Thermolytical techniques to characterize fungal polysaccharides and bacterial
      lipopolysaccharides.
AB  - The present work constitutes an entirely novel contribution in the scope of
      microbiology and especially in taxonomy, introducing thermolysis curves as a
      rapid method of characterization of fungal polysaccharides and bacterial
      lipopolysaccharides. The thermal analysis techniques applied were
      thermogravimetry and derivative thermogravimetry (TG-DTG), differential thermal
      analysis (DTA), and differential scanning calorimetry (DSC). Each thermogram of a
      sample is represented by one or a few temperatures and, in DSC, by complementary
      enthalpy data. The temperatures of the thermograms from structurally unknown
      polysaccharides are compared with those used as references, and thus, information
      on their composition, linkage types, and anomeric configuration can be deduced.
      The situation is more complicated for bacterial lipopolysaccharides, but in
      whatever mode, a structural estimation is always possible. In the course of the
      development and validation of the thermal method, structural findings on relative
      stabilities of linkage types (valuable in carbohydrate research) have been
      recognized and are therefore also described in this work.

PMID- 1367754
TI  - Nonlinear gradient isotherm parameter estimation for proteins with consideration
      of salt competition and multiple forms.
AB  - Salt gradients in ion-exchange chromatography are routinely used to speed
      separation of proteins and to concentrate products, but systematic optimization
      of these gradients requires protein equilibrium data as a function of salt
      concentration. An understanding of conformational changes, aggregation, and salt
      effects, which include both competition and affinity modulation, is important for
      equilibrium isotherm parameter estimation. In this study, gradient elution of
      bovine serum albumin (BSA) in anion exchange was well predicted by a salt
      modulated nonlinear isotherm which considers salt competition. The isotherm was
      able to predict BSA gradient elution from batch equilibrium data. The same
      isotherm was also able to predict elution for various gradient slopes when fitted
      to an intermediate slope gradient experiment. If multiple forms due to
      aggregation or denaturation exist, isotherm parameters are readily averaged in
      batch experiments because of the long equilibration times. Similarly, gradient
      experiments yield averaged parameters because the salt gradient tends to merge
      the closely eluting forms. However, in isocractic elution, if the reaction rate
      is not rapid enough to give a merged peak, the estimated isotherm parameters are
      only fair predictors of gradient behavior and vice versa. Slower flow rates in
      isocratic elution can help reduce the discrepancy by allowing forms to merge
      through interconversion. As an alternative to determining averaged parameters,
      consideration of two binding forms, using VERSE-LC, an advanced rate model, gave
      good agreement with experimental data over the entire range of salt gradient
      durations.

PMID- 1367755
TI  - Intracellular ice formation during the freezing of hepatocytes cultured in a
      double collagen gel.
AB  - During freezing, intracellular ice formation (IIF) has been correlated with loss
      in viability for a wide variety of biological systems. Hence, determination of
      IIF characteristics is essential in the development of an efficient methodology
      for cryopreservation. In this study, IIF characteristics of hepatocytes cultured
      in a collagen matrix were determined using cryomicroscopy. Four factors
      influenced the IIF behavior of the hepatocytes in the matrix: cooling rate, final
      cooling temperature, concentration of Me2SO, and time in culture prior to
      freezing. The maximum cumulative fraction of cells with IIF increased with
      increasing cooling rate. For cultured cells frozen in Dulbecco's modified Eagle's
      medium (DMEM), the cooling rate for which 50% of the cells formed ice (B50) was
      70 degrees C/min for cells frozen after 1 day in culture and decreased to 15
      degrees C/min for cells frozen after 7 days in culture. When cells were frozen in
      a 0.5 M Me2SO + DMEM solution, the value of B50 decreased from 70 to 50 degrees
      C/min for cells in culture for 1 day and from 15 to 10 degrees C/min for cells in
      culture for 7 days. The value of the average temperature for IIF (TIIF) for
      cultured cells was only slightly depressed by the addition of Me2SO when compared
      to the IIF behavior of other cell types. The results of this study indicate that
      the presence of the collagen matrix alters significantly the IIF characteristics
      of hepatocytes. Thus freezing studies using hepatocytes in suspension are not
      useful in predicting the freezing behavior of hepatocytes cultured in a collagen
      matrix. Furthermore, the weak effect of Me2SO on IIF characteristics implies that
      lower concentrations of Me2SO (0.5 M) may be just as effective in preserving
      viability. Finally, the value of B50 measured in this study indicates that
      cooling rates nearly an order of magnitude faster than those previously
      investigated could be used for cryopreservation of the hepatocytes in a collagen
      gel.

PMID- 1367756
TI  - DNA-based drugs, diagnostics and devices.

PMID- 1367757
TI  - Detection of nucleic acid hybridization using surface plasmon resonance.

PMID- 1367758
TI  - Oligonucleotides: problems and frontiers of practical applications.

PMID- 1367759
TI  - Cofactor engineering.

PMID- 1367760
TI  - The role of N-linked oligosaccharides in glycoprotein function.
AB  - N-linked glycoproteins include such biologically important molecules as cell
      surface receptors, cell-adhesion molecules, immunoglobulins and other serum
      proteins, and tumor antigens. Investigating the role of carbohydrate in
      glycoprotein function has included the use of glycosylation inhibitors or site
      directed mutagenesis of specific glycosylation sites to prevent the addition of
      carbohydrate, or glycosylation processing inhibitors or animal cell glycosylation
      mutants to alter carbohydrate structure. In some proteins, glycosylation plays an
      important role in recognition, while in others, it may stabilize and/or control
      the conformation of the protein. The cloning of genes in bacteria or lower
      eukaryotes--with the goal of producing biologically active proteins for
      biotechnological purposes--necessitates a better understanding of the role of
      specific carbohydrate structures.

PMID- 1367761
TI  - Developing rDNA products for treatment of hemophilia A.
AB  - Current therapy for hemophilia A requires frequent infusion of plasma-derived
      human factor VIII with the associated drawbacks of potential viral contamination,
      high cost and limited plasma availability. Factor VIII replacement therapy has
      been improved through increased knowledge of molecular mechanisms regulating
      blood coagulation, derived largely from the isolation of the factor VIII gene and
      its expression in mammalian cells. Homogeneous pure preparations of factor VIII-
      the largest, most complex protein pharmaceutical produced to date through
      recombinant DNA technology--can now be produced for successful treatment of
      hemophilia A.

PMID- 1367762
TI  - Checking sources: the serum supply secret.

PMID- 1367764
TI  - Tracking trends in U.S. biotechnology.

PMID- 1367763
TI  - The anatomy of access: peptide drug delivery.

PMID- 1367766
TI  - The loneliness of the long-distance gel-runner.

PMID- 1367765
TI  - Pharmaceutical price control: will governments harmonize regulations?

PMID- 1367767
TI  - LIMS and the Human Genome Project.

PMID- 1367768
TI  - The oligosaccharides of glycoproteins: bioprocess factors affecting
      oligosaccharide structure and their effect on glycoprotein properties.
AB  - In this review, we organize the recent data concerning the effects of bioprocess
      factors on the oligosaccharide structure of human therapeutic glycoproteins, with
      particular emphasis on the influence of the host cell. We also discuss the effect
      of oligosaccharide structure on glycoprotein properties, including antigenicity,
      immunogenicity and plasma clearance rate.

PMID- 1367769
TI  - Targeting recombinant antibodies to the surface of Escherichia coli: fusion to a
      peptidoglycan associated lipoprotein.
AB  - To target recombinant antibodies to the surface of Escherichia coli, we have
      fused single-chain variable domains to its peptidoglycan associated lipoprotein
      (PAL). The fusion protein was able to bind antigen and was tightly bound to the
      murein layer of the cell envelope. Antibody-PAL had little effect on cell growth
      and viability. In contrast, the expression of single chain antibody alone
      eventually resulted in cell lysis. Immunofluorescence studies on unfixed cells
      showed that functional antibodies were accessible at the surface of intact
      bacteria. This could provide a means of isolating single cells producing specific
      antibodies from libraries in E. coli by fluorescence assisted cell sorting
      (FACS). Pal fusions may also be of general interest for the presentation of
      proteins at the surface of E. coli as, for example, in the production of live
      vaccines.

PMID- 1367770
TI  - A streptavidin-protein A chimera that allows one-step production of a variety of
      specific antibody conjugates.
AB  - We have expressed a gene fusion of streptavidin and the two immunoglobulin G
      (IgG)-binding domains of protein A in Escherichia coli. The purified chimeric
      protein had full biotin-binding ability, and bound one IgG molecule per subunit
      (31.4 kD). The affinity of the chimeric protein both for biotin and IgG can be
      used to provide antibody molecules with additional recognition capabilities. For
      example, the chimera will allow any IgG molecule to be used for sensitive biotin
      linked detection systems without the need for chemical modification.

PMID- 1367771
TI  - Evaluation of foreign gene codon optimization in yeast: expression of a mouse IG
      kappa chain.
AB  - We have optimized the codons in an immunoglobulin kappa chain gene to those
      preferred in the yeast Saccharomyces cerevisiae. The mutant and wild type kappa
      chain genes were each fused with a synthetic invertase signal peptide that also
      contained only yeast-preferred codons, and expressed in the F762 yeast strain.
      The use of yeast-preferred codons resulted in a more than 5-fold increase in the
      rate of synthesis and at least a 50-fold increase in the steady state level of
      protein.

PMID- 1367772
TI  - On the safety of Bacillus subtilis and B. amyloliquefaciens: a review.

PMID- 1367773
TI  - Degradation of dioxane, tetrahydrofuran and other cyclic ethers by an
      environmental Rhodococcus strain.
AB  - By enrichment and isolation techniques bacterial strains with the capacity to
      grow on aliphatic cyclic ethers (dioxane, tetrahydrofuran, 1,3-dioxolane) have
      been isolated. Six strains that degrade tetrahydrofuran were classified as
      belonging to the genus Rhodococcus. One of two strains that degrade dioxane
      instead of or in combination with tetrahydrofuran was further characterized and a
      hypothetical catabolic pathway comprising an initial 2-hydroxylation and several
      oxidation steps is postulated.

PMID- 1367774
TI  - Optimization of growth conditions for the production of proteolytically-sensitive
      proteins in the periplasmic space of Escherichia coli.
AB  - The expression of many secreted recombinant proteins in Gram-negative bacteria is
      limited by degradation in the periplasmic space. We have previously shown that
      the production of protein A-beta-lactamase, a secreted fusion protein highly
      sensitive to proteolysis in Escherichia coli, can be increased in mutant strains
      deficient in up to three cell-envelope-associated proteolytic activities. In this
      work we investigated the effect of fermentation conditions on suppressing any
      residual proteolytic activity in various protease-deficient strains. Optimal
      production of the fusion protein was observed in cells grown under mildly acidic
      conditions (5.5 less than or equal to pH less than or equal to 6.0) and a low
      temperatures. These conditions were shown to specifically decrease the rate of
      proteolysis. In addition, a further increase in production was observed in
      cultures supplemented with 0.5 to 0.75 mM zinc chloride. This may relate to the
      inhibition of a cell envelope protease by Zn2+ ions.

PMID- 1367775
TI  - Optimization of Candida tropicalis cytochrome P450alk gene expression in
      Saccharomyces cerevisiae with continuous cultures.
AB  - The cytochrome P450alk gene (P45alk) from Candida tropicalis ATCC 750 was
      expressed in Saccharomyces cerevisiae GRF18 under control of the alcohol
      dehydrogenase I (ADHI) promoter. To achieve stable expression over long time
      periods, a 2-microns derived replicative and an integrative expression system
      were tested in continuous culture. The 2-microns derived replicative system could
      not be maintained in cells over high generation numbers. In continuous culture,
      the instability was more pronounced at high dilution rates (D) and high histidine
      concentration, for which the yeast is auxotrophic. The nature of the instability
      was probably due to a gene conversion event between the plasmid and the yeast
      chromosome. In contrast, the integrative expression system was stably maintained
      in cells over prolonged cultivation times. Since this work focused on the
      production of large quantities of P450 by heterologous expression in yeast over
      prolonged time periods, the integrant was used to optimize P450alk expression by
      varying continuous culture parameters. The P450alk expression was shown to be
      dependent on the D applied to the culture. The highest P450alk expression levels
      were obtained at high D, when cell metabolism was shifted to partial glucose
      oxidation, yielding ethanol as a major metabolite in the culture supernatant. In
      contrast, when glucose was completely oxidized at low D, the ADHI-dependent
      P450alk expression was reduced and followed by a corresponding decrease in
      heterologous protein.

PMID- 1367776
TI  - Biosurfactants from Bacillus licheniformis: structural analysis and
      characterization.
AB  - The surface-active compounds of the strain Bacillus licheniformis were isolated
      and their structure was elucidated. The high surface-active capacity of the crude
      extract was basically due to traces of long-chain saturated fatty acids,
      especially of palmitic and stearic acids, to a mixture of small amounts of
      hydrocarbons with chain lengths of 20 and 22 carbons, and mainly to appreciable
      amounts of four slightly different lipopeptides. The lipopeptides were found to
      be a mixture of four closely related compounds. The lipophilic part consisting of
      i-, n-C14 or i-, ai-C15 beta-OH fatty acids was linked to the hydrophilic peptide
      moiety, which contained seven amino acids (Glu, Asp, Val, three Leu and Ile) by a
      lactone linkage. Fifteen milligrams per litre of the purified lipopeptide product
      decreased the surface tension of water from 72 mN m-1 to 27 mN m-1,
      characterizing the product as a powerful surface-active agent that compares
      favourably to other (bio)surfactants. Antibiotic activity was demonstrated
      against bacteria and yeasts.

PMID- 1367777
TI  - Production of heterologous proteins in Bacillus subtilis: the effect of the joint
      between signal sequence and mature protein on yield.
AB  - We have previously made a set of DNA constructs by fusing the mature part of
      Bacillus licheniformis alpha-amylase with the signal sequence of B.
      amyloliquefaciens alpha-amylase at various distances from the signal sequence
      cleavage site. We observed that the level of alpha-amylase production in B.
      subtilis depended strongly on the distance of the junction from the signal
      sequence cleavage site, with quite a sharp optimum distance. To test whether the
      effect is limited to the pair of alpha-amylase signal sequence and mature
      protein, we analysed the protein production in a set of constructs in which an
      Escherichia coli beta-lactamase was similarly joined at different distances from
      the alpha-amylase signal sequence. Also in this case the distance seemed to be an
      important factor in affecting the level of production in B. subtilis. The
      observed effect might depend on the modulation of pre-protein folding, which in
      turn could affect the secretion level.

PMID- 1367778
TI  - Use of high density cultures of Escherichia coli for high level production of
      recombinant Pseudomonas aeruginosa exotoxin A.
AB  - An efficient fermentation method for the production of two modified recombinant
      Pseudomonas aeruginosa exotoxin As cloned in Escherichia coli BL21(lambda DE3)
      was developed. Cell densities of 16-30 g dry weight/1 were found to be most
      suitable for the induction of protein synthesis, which was under the isopropyl
      beta-D-thiogalactopyranoside (IPTG)-inducible T7 expression system. A
      concentration of 0.6 mM IPTG and induction time of 90 min were found to give the
      best results for production of the modified toxins. Using this procedure, gram
      amounts of the proteins were obtained in a 3-1 bench-top fermentor. The high
      density growth of the bacteria did not impair the integrity of the proteins and
      did not interfere with the purification procedure.

PMID- 1367779
TI  - Comparison of the amino acid sequences of the lectins from seeds of Dioclea
      lehmanni and Canavalia maritima.
AB  - The amino acid sequences of the major lectins from the seeds of Dioclea lehmanni
      and Canavalia maritima were determined by DABITC/PITC microsequence analysis of
      peptides derived from the proteins by enzymatic digestions with trypsin,
      chymotrypsin and the protease from S. aureus V8. These sequences were found to be
      very similar to those of the lectins from Dioclea grandiflora and Canavalia
      ensiformis (Con A). The D. lehmanni lectin was unusual amongst legume lectins in
      that it contained a single Cys.

PMID- 1367780
TI  - Three saponins from Oxytropis species.
AB  - Three flavonoids and three saponins have been isolated from Oxytropis species.
      Their structures were determined as isorhamnetin-3-O-beta-D-glucoside, rhamnetin
      3-O-beta-D-galactoside, apigenin, 3-O-[alpha-L-rhamnopyranosyl (1----2)-beta-D
      glucopyranosyl(1----4)-beta-D-glucuronopyranosyl]+ ++soyasapogenol B, 3-O-[beta-D
      glucopyranosyl(1----2)-beta-D-glucuronopyranosyl] azukisapogenol and a new
      saponin 3-O-[beta-D-glucopyranosyl(1----2)-beta-D-glucopyranosyl]-25-O-alpha-L-
      rhamnopyranosyl-(20S,24S)-3 beta,16 beta, 20,24,25-pentahydroxy-9,19
      cycloanostane.

PMID- 1367781
TI  - Triterpene saponins from Cylicodiscus gabunensis.
AB  - Four new saponins were isolated from the alcoholic extract of the bark of
      Cylicodiscus gabunensis by means of flash chromatography. They were characterized
      on the basis of spectral and chemical data as 3-O-beta-[alpha-L-arabinopyranosyl
      (1----2),alpha-L-arabinopyranosyl(1----3),beta-D-glucopyranosyl(1- ---)] maslinic
      acid-28-[beta-D-glucopyranosyl(1----6),beta-D-glucopyranosyl(1----2),alp ha-L-
      rhamnopyranosyl(1----)] ester; 3-O-beta-[alpha-L-arabinopyranosyl(1----2),alpha-L
      arabinopyran osyl (1----3),beta-D-glucopyranosyl(1----)]maslinic acid-28-[beta-D
      glucopyranosyl(1----2),alpha-L-rhamnopyranosyl(1----)] ester, 3-O-beta-[alpha-L
      arabinopyranosyl(1----2),alpha-L-arabinopyran osyl (1----3),beta-D
      glucopyranosyl(1----)]maslinic acid and 3-O-beta(alpha-L-arabinopyranosyl(1---
      3),beta-D-glucopyranosyl (1----)] cylicodiscic acid.

PMID- 1367782
TI  - A sulphated triterpenoid saponin from Schefflera octophylla.
AB  - Dried leaves of Schefflera octophylla afforded a new sulphated triterpene
      glycoside. From spectroscopic data and chemical transformations the structure of
      the new constituent was determined as 3-epi-betulinic acid 3-O-sulphate 28-O
      [alpha-L-rhamnopyranosyl(1----4)-O-beta-D-glucopyranosyl (1----6)]-beta-D
      glucopyranoside.

PMID- 1367784
TI  - Two flavonol glycosides, hexandrasides C and D, from the underground parts of
      Vancouveria hexandra.
AB  - In addition to four known glycosides, icariin, epimedin B, epimedosides A and E,
      two new glycosides of a flavonol with a gamma,gamma-dimethylallyl group were
      isolated from the underground parts of Vancouveria hexandra. The structures were
      determined to be des-O-methyl-anhydroicaritin 3-O-beta-D-xylopyranosyl(1----2)
      alpha-L-rhamnopyranoside 7-O-beta-D-glucopyranosyl(1----2)-beta-D-glucopyranoside
      and anhydroicaritin 3-O-alpha-L-rhamnopyranosyl(1----3)-alpha-L-rhamnopyranoside
      7-O-beta-D-glucopyranoside by means of spectral analysis.

PMID- 1367783
TI  - Flavonoid glycosides from Cassia alata.
AB  - Two new glycosides, chrysoeriol-7-O-(2"-O-beta-D-mannopyranosyl)-beta-D
      allopyranos ide and rhamnetin-3-O-(2"-O-beta-D-mannopyranosyl)-beta-D
      allopyranosid e, were isolated from the seeds of Cassia alata. The structures
      were established on the basis of chemical evidence and spectroscopic methods,
      especially NMR.

PMID- 1367785
TI  - Saponins from Deutzia corymbosa.
AB  - Two new saponins were isolated from Deutzia corymbosa and characterized as:
      echinocystic acid-3-O-[alpha-L-arabinopyranosyl(1----4)]alpha-L-
      arabinopyranoside and echinocystic acid-3-O-[beta-D-galactopyranosyl(1----4)alpha
      L- rhamnopyranosyl(1----4)]alpha-L-arabinopyranoside. Umbellferone and sitosterol
      beta-D-glucoside were also isolated and characterized.

PMID- 1367786
TI  - Xyloglucan oligosaccharide alpha-L-fucosidase activity from growing pea stems and
      germinating nasturtium seeds.
AB  - [14C]Fucose-labelled xyloglucan (XG) was synthesized from tamarind seed XG by
      incubating it with GDP-[14C]fucose plus solubilized pea fucosyltransferase, and
      [14C]fucose-labelled XG nonasaccharide was prepared from the parent hemicellulose
      by partial hydrolysis with fungal cellulase. alpha-L-Fucosidase activity was
      readily detected in crude enzyme extracts of growing regions of etiolated pea
      stems (Pisum sativum) and in cotyledons of germinating nasturtium seedlings
      (Tropaeolum majus) using the fucosylated XG-nonasaccharide as substrate. Both
      enzymes showed little activity against intact fucosylated XG and they were
      totally inactive against p-nitrophenyl-alpha-L-fucoside. Auxin treatment of pea
      stems, which greatly increased the activity of endo-1,4-beta-glucanases that
      hydrolyse XG in apical growing regions, failed to result in a similar increase in
      XG-nonasaccharide alpha-fucosidase activity. However, germination of nasturtium
      seed, which resulted in a large increase in endo-1,4-beta-glucanase (XG-ase)
      activity in the cotyledons, was accompanied by comparable increases in XG-alpha
      fucosidase activity.

PMID- 1367787
TI  - A monoclonal antibody to scopolamine and its use for competitive enzyme-linked
      immunosorbent assay.
AB  - A hybridoma clone producing a monoclonal antibody (SC78.H81) against scopolamine
      was established. The monoclonal antibody was an IgG1 (k) antibody with high
      affinity (1.6 x 10(9) M-1 for methylscopolamine). The monoclonal antibody was
      cross-reactive with methylscopolamine and butylscopolamine, and showed weak cross
      reactivity with 6 beta- and 7 beta-hydroxyhyoscyamine. The cross-reaction with L
      hyoscyamine, atropine, scopine and DL-tropic acid was very weak. A competitive
      enzyme-linked immunosorbent assay using SC78.H81 was established to quantify
      scopolamine. The sensitivity of the assay allowed detection of 20 pg assay-1 (0.2
      ng ml-1) of scopolamine. The assay was applied to the estimation of scopolamine
      content in hairy root cultures of a Duboisia hybrid.

PMID- 1367788
TI  - Triterpenoid saponins from Medicago hispida.
AB  - Soyasaponin III has been characterized and the structure of a new triterpenoid
      saponin, hispidacin, has been elucidated as soyasapogenol B-3-O-alpha-L
      rhamnopyranopyranosyl(1----2)- beta-D-glucopyranosyl(1----2)-beta-D
      glucuronopyranoside by a combination of fast-atom bombardment mass spectrometry,
      13C NMR spectroscopy, and some chemical transformations. Mechanism of
      transformation of soyasapogenol B to soyasapogenols D, and F has also been
      rationalized.

PMID- 1367789
TI  - Triterpene saponins from Verbascum songaricum.
AB  - Songarosaponin A, B and C isolated from the aerial parts of Verbascum songaricum
      were shown to be 3-O-[alpha-L-rhamnopyranosyl-(1----4)-beta-D-glucopyranosyl-(1--
      -3)]-[b eta-D-glucopyranosyl-(1----2)-beta-D-fucopyranosyl]-olea-11,13-die ne-3
      beta-23,28-triol, 3-0-[alpha-L-rhamnopyranosyl-(1----4)-beta-D-glucopyranosyl-(1-
      --3)]-[b eta-D-glucopyranosyl-(1----2)]-beta-D-fucopyranosyl]-olea-1 1-ene-3 beta
      13,23,28-tetrol and 3-O-[beta-D-glucopyranosyl-(1----4)]-[beta-D-glucopyranosyl
      (1----3)]-[b eta-D-glucopyranosyl-(1----2)]-beta-D-fucopyranosyl]-13 beta,28
      epoxyolea-11-ene-3 beta,23-diol.

PMID- 1367790
TI  - Three triterpenoid saponins from Triplostegia grandiflora.

PMID- 1367791
TI  - Steroidal saponins from the rhizomes of Polygonatum orientale.

PMID- 1367792
TI  - The complete amino acid sequence of the major Kunitz trypsin inhibitor from the
      seeds of Prosopsis juliflora.
AB  - The major inhibitor of trypsin in seeds of Prosopsis juliflora was purified by
      precipitation with ammonium sulphate, ion-exchange column chromatography on DEAE-
      and CM-Sepharose and preparative reverse phase HPLC on a Vydac C-18 column. The
      protein inhibited trypsin in the stoichiometric ratio of 1:1, but had only weak
      activity against chymotrypsin and did not inhibit human salivary or porcine
      pancreatic alpha-amylases. SDS-PAGE indicated that the inhibitor has a Mr of ca
      20,000, and IEF-PAGE showed that the pI is 8.8. The complete amino acid sequence
      was determined by automatic degradation, and by DABITC/PITC microsequence
      analysis of peptides obtained from enzyme digestions of the reduced and S
      carboxymethylated protein with trypsin, chymotrypsin, elastase, the Glu-specific
      protease from S. aureus and the Lys-specific protease from Lysobacter
      enzymogenes. The inhibitor consisted of two polypeptide chains, of 137 residues
      (alpha chain) and 38 residues (beta chain) linked together by a single disulphide
      bond. The amino acid sequence of the protein exhibited homology with a number of
      Kunitz proteinase inhibitors from other legume seeds, the bifunctional
      subtilisin/alpha-amylase inhibitors from cereals and the taste-modifying protein
      miraculin.

PMID- 1367793
TI  - Relationship of the flavodoxin isoforms from Porphyra umbilicalis.
AB  - The macroalga Porphyra umbilicalis contained two flavodoxins in approximately 5:1
      ratio and differing in Mr by ca 1000. The N-terminal sequences of the isoforms
      were identical and there was strong immunochemical identity. Peptide mapping gave
      similar fragments which differed in Mr by constant amount for the two isoforms.
      The flavodoxins may therefore differ only at the C-terminus, possibly as a
      consequence of in vivo processing since inclusion of protease inhibitors during
      extraction had no effect on the ratio of the isoforms.

PMID- 1367794
TI  - Water-soluble polysaccharides from Ginkgo biloba leaves.
AB  - The water-soluble polysaccharides from dried Ginkgo biloba leaves were isolated
      after exhaustive extraction with organic solvents. The polysaccharide mixture
      could be separated into a neutral (GF1) and two acidic (GF2 and GF3)
      polysaccharide fractions by ion exchange chromatography. According to the Mr
      distribution GF1 and GF3 seemed to be homogenous, whereas GF2 could be further
      fractionated into two subfractions (GF2a and GF2b) by gel permeation
      chromatography. GF1 (Mr 23,000) showed the structural features of a branched
      arabinan. The main chain was composed of 1,5-linked arabinose residues and three
      in 12 arabinose molecules were branched via C-2 or C-3. GF2a (Mr 500,000)
      consisted mainly of 1,2,4-branched mannose (29%), 1,4-linked glucuronic (32%) and
      galacturonic (8%) acid as well as terminal rhamnose (25%). After removal of ca
      70% of the terminal rhamnose the remaining polysaccharide showed a decrease in
      1,2,4-branched mannose and an increase in 1,2-linked mannose indicating that at
      least half of the rhamnose residues were linked to mannose via C-4. GF3 (Mr
      40,000) consisted of 1,4-linked galacturonic (30%) and glucuronic (16) acid,
      1,3,6-branched galactose (15%), 1,2-linked (5%) and 1,2,4-branched (3.5%)
      rhamnose as well as 1,5-linked arabinose (11%). Rhamnose (5%) and arabinose (10%)
      were present as terminal groups. Mild acid hydrolysis selectively cleaved
      arabinose and the remaining polysaccharide showed an increased amount of 1,6
      linked and terminal galactose and a decreased quantity of 1,3,6-branched
      galactose. These results indicated that the terminal as well as the 1,5-linked
      arabinose were mainly connected to galactose via C-3. The GF3 polysaccharide
      appeared to be a rhamnogalacturonan with arabinogalactan side chains.

PMID- 1367795
TI  - A C13-norisoprenoid gentiobioside from quince fruit.
AB  - The beta-D-gentiobioside [beta-D-glucopyranosyl(1----6)-beta-D-glucopyranoside]
      of 3-hydroxy-beta-ionol has been isolated and characterized in quince (Cydonia
      oblonga) fruit through spectral and chemical studies. Model experiments carried
      out with this new natural compound revealed its important role as precursor of a
      number of C13-norisoprenoid flavour compounds of quince essential oil.

PMID- 1367796
TI  - A spirostanol glycoside from Cestrum nocturnum.
AB  - A new steroidal saponin named nocturnoside A has been isolated from the
      methanolic extract of the fresh leaves of Cestrum nocturnum and has been
      characterized by 13C NMR spectroscopy to be 3-O-[beta-D-glucopyranosyl(1----3)
      beta-D-glucopyranosyl(1----2)-beta-D- glucopyranosyl((3----1)-beta-D
      xylopyranosyl)(1----4)-beta-D- galactopyranosyl) (25R)-spirost-5-ene-2 alpha,3
      beta-diol.

PMID- 1367797
TI  - Phlinosides D and E, phenylpropanoid glycosides, and iridoids from Phlomis
      linearis.
AB  - Two new phenylpropanoid glycosides, phlinosides D and E were isolated from the
      methanolic extract of the aerial parts of Phlomis linearis, along with the known
      iridoid glucosides, lamiide, ipolamiide and auroside (= 5-hydroxy-8-epiloganin).
      On the basis of chemical and spectral evidence the structures of phlinosides D
      and E were determined as 3,4-dihydroxy-beta-phenylethoxy-O-beta-D-xylopyranosyl
      (1----2)-al pha-L-rhamnopyranosyl-(1----3)-4-O-feruloyl-beta-D-glucopyranoside
      and 3,4-dihydroxy-beta-phenylethoxy-O-alpha-L-rhamnopyranosyl-(1----2) -alpha-L-
      rhamnopyranosyl-(1----3)-4-O-feruloyl-beta-D-glucopyranoside, respectively.

PMID- 1367798
TI  - Flavonol and anthraquinone glycosides from Rhamnus formosana.
AB  - Two new flavonol triglycosides, and a new anthraquinone glycoside, have been
      isolated from the roots of Rhamnus formosana. These compounds have been
      characterized as rhamnazin 3-O-[alpha-L-rhamopyranosyl(1----4)-alpha-L
      rhamnopyranosyl(1----6 )]-beta-D-galactopyranoside (rhamnazin 3-isorhamninoside),
      rhamnocitrin 3-O-isorhamninoside and 1,6,8-trihydroxy-3-methylanthraquinone 1-O
      rhamnosyl(1----2)glucoside, respectively.

PMID- 1367799
TI  - Expression of streptomycete cholesterol oxidase in Escherichia coli.
AB  - A streptomycete gene coding for extracellular cholesterol oxidase (choA) was
      subcloned and expressed in Escherichia coli. The pUCO series recombinants were
      obtained by inserting the choA gene into the unique KpnI site of pUC19 vector.
      Expression was observed with pUCO192A and pUCO193 constructs in which the cloned
      gene(s) were aligned with the upstream lacZ promoter. Isopropyl beta-D
      thioglucopyranoside (IPTG) enhanced this expression up to 2.5-fold. Specific Cho
      activity in the cell extracts of the stable pUCO193 transformant were 0.004 U and
      0.007 U per mg protein without and with IPTG induction, respectively. Cho
      activity was detected in the spent medium of this culture, suggesting possible
      secretion of the enzyme.

PMID- 1367800
TI  - Delta'-dehydrogenation of steroids by Arthrobacter simplex immobilized in calcium
      polygalacturonate beads.
AB  - Arthrobacter simplex ATCC 6946 (viable cells) was immobilized in a calcium
      polygalacturonate gel. The trapped cells were used for repeated batchwise
      bioconversion of steroids. Reichstein's compound S and hydrocortisone were
      dehydrogenated introducing a double bond between C1 and C2 of ring A. The
      products 1-dehydro S and prednisolone, respectively, were identified by high
      pressure liquid chromatography. Steroid dehydrogenase activity increased in the
      system when an artificial electron acceptor, such as menadione (vitamin K3) was
      present in the reaction mixture. An airlift-type reactor was used to bioconvert
      up to 90% of substrate in 15 min, under optimal conditions. The gel entrapped
      cell preparations were used for repeated batch bioconversion during 30 days; 69
      batch bioconversions for Reichstein's compound S were performed during 15 days of
      operation of the reactor. The operational stability of the process and the
      feasibility of repeated batch bioconversions was shown to be comparable to
      similar processes.

PMID- 1367801
TI  - The biosynthetic origin of the pyridone ring of efrotomycin.
AB  - Nocardia lactamdurans has been shown to catabolyse uracil via the reductive
      pathway. The end product of this pathway, beta-alanine, is incorporated into the
      pyridone ring of efrotomycin. Support for this proposal includes: (1) reversal of
      thymine inhibition of efrotomycin biosynthesis by dihydrouracil and N-carbamoyl
      beta-aline, two intermediates of the catabolic pathway; (2) incorporation of [5,6
      3H]-uracil into efrotomycin with a relative molar specific activity of
      approximately 0.5, close to the theoretical maximum; and (3) 13C coupling at C4
      and C5 of efrotomycin after feeding resting cells with [4,5-13C]-uracil. Our
      results do not rule out the possibility of an alternative source of beta-alanine
      or the coexistence of uracil catabolism via oxidative reactions.

PMID- 1367803
TI  - Mastering Biology.

PMID- 1367802
TI  - Characterizing recombinant proteins.

PMID- 1367804
TI  - A rejection profile test for ultrafiltration membranes & devices.

PMID- 1367805
TI  - Products in the U.S. pipeline. Pharmaceutical Manufacturers Association.

PMID- 1367806
TI  - Stable multicopy vectors for high-level secretion of recombinant human serum
      albumin by Kluyveromyces yeasts.
AB  - We have designed stable pKD1 derivatives for efficient secretion of recombinant
      human serum albumin (rHSA) by industrial strains of Kluyveromyces yeasts. A
      comparison of this multi-copy expression system with isogenic cassettes
      integrated at chromosomal loci demonstrated that high level secretion of rHSA is
      a function of gene dosage in K. lactis. Various signal sequences could be used,
      and the secretion levels were independent of the presence of the native pro
      peptide. The mitotic stability of the pKD1-based expression vectors was found to
      be species and strain dependent and was influenced by promoter strength and
      culture conditions. Vector stability was drastically enhanced when the HSA gene
      was expressed from an inducible promoter: 90% of the transformed cells still
      harbored the vector after 100 generations of non-selective growth in uninduced
      culture conditions. Secretion levels in the range of several grams per liter of
      correctly folded and processed rHSA were obtained at the pilot scale, thus making
      the industrial production of pharmaceutical-grade, Kluyveromyces-derived rHSA
      economically feasible.

PMID- 1367807
TI  - High albumin production by multicellular spheroids of adult rat hepatocytes
      formed in the pores of polyurethane foam.
AB  - Adult rat hepatocytes formed spherical multicellular aggregates (spheroids) when
      they were cultured in the pores of polyurethane foam (PUF). The diameter of the
      spheroids was within the range 100-200 microns. These spheroids partly attached
      and immobilized in the PUF pores for at least 2 weeks. The albumin production
      rate by the spheroids increased up to 17.0 micrograms/10(6) nuclei per day during
      the first 6 days and maintained at a high level for 2 weeks. In contrast, the
      albumin production rate by the monolayer markedly decreased after 3 days. The
      spheroid culture using PUF seems to be a convenient and simple method for
      maintaining some differentiated functions of hepatocytes and for making a
      bioreactor using the function of spheroids.

PMID- 1367808
TI  - Molecular cloning and nucleotide sequence determination of the Bacillus
      stearothermophilus NCA 1503 superoxide dismutase gene and its overexpression in
      Escherichia coli.
AB  - The gene (sod) encoding Bacillus stearothermophilus Mn-superoxide dismutase
      (MnSOD) has been cloned in Escherichia coli and its entire nucleotide sequence
      determined. With the exception of the post-translationally cleaved N-terminal
      methionine residue, the predicted amino acid sequence exhibits complete identity
      to the previously determined amino acid sequence. The recombinant MnSOD was shown
      to be functionally active in E. coli both in vitro and in vivo, and was expressed
      to 49% of the soluble cell protein by coupling its transcription to the E. coli
      trp promoter. The sequenced region of DNA was also found to encompass a second
      open reading frame. The putative encoded polypeptide exhibited no significant
      primary sequence homology to any currently characterised protein.

PMID- 1367809
TI  - Transformation of trichloroethylene by sulfate-reducing cultures enriched from a
      contaminated subsurface soil.
AB  - Trichloroethylene (TCE) was reductively dechlorinated to cis-1,2-dichloroethylene
      (cDCE) by sulfate-reducing cultures enriched from a contaminated subsurface soil.
      The highest observed transformation rate of TCE was 213 mumol l-1 per day at 35
      degrees C. The predominant biotransformation product was cDCE. However, further
      dechlorination of cDCE was not observed in most of the cultures. Methane
      production was insignificant and active sulfate reduction was achieved by
      maintaining excess sulfate. A comparison of sodium sulfide and sodium dithionite
      for their effect on the transformation of TCE revealed that the latter is a
      better reducing agent. The extent of TCE transformation in 25 days was ca. 20%
      higher in the dithionite-amended cultures. A decrease in the rate and extent of
      TCE transformation was observed with an increase in the concentration of
      bromoethanesulfonate up to 50 mM.

PMID- 1367810
TI  - Alginate as immobilization matrix and stabilizing agent in a two-phase liquid
      system: application in lipase-catalysed reactions.
AB  - Alginate was evaluated as an immobilization matrix for enzyme-catalyzed reactions
      in organic solvents. In contrast to most hydrogels, calcium alginate was found to
      be stable in a range of organic solvents and to retain the enzyme inside the gel
      matrix. In hydrophobic solvents, the alginate gel (greater than 95% water) thus
      provided a stable, two-phase liquid system. The lipase from Candida cylindracea,
      after immobilization in alginate beads, catalysed esterification and
      transesterification in n-hexane under both batch and continuous-flow conditions.
      The operational stability of the lipase was markedly enhanced by alginate
      entrapment. In the esterification of butanoic acid with n-butanol, better results
      were obtained in the typical hydrophilic calcium alginate beads than in less
      hydrophilic matrices. The effects of substrate concentration, matrix area, and
      polarity of the substrate alcohols and of the organic solvent on the
      esterification activity were examined. The transesterification of octyl 2
      bromopropanoate with ethanol was less efficient than that of ethyl 2
      bromopropanoate with octanol. By using the hydrophilic alginate gel as an
      immobilization matrix in combination with a mobile hydrophobic phase, a two-phase
      liquid system was achieved with definite advantages for a continuous, enzyme
      catalysed process.

PMID- 1367811
TI  - Controlling and predicting monoclonal antibody production in hollow-fiber
      bioreactors.
AB  - A simple optimization strategy is described which enables monoclonal antibody
      (MCA) production in hollow-fiber bioreactors to be controlled and predicted. The
      MCA production rate is demonstrated to increase linearly with the uptake rates of
      glucose and glutamine and with the production rates of lactate and ammonia. The
      uptake and production rates of these metabolites can, in turn, be predicted from
      the pumping rates of basal medium to the bioreactor. We recommend a period of 2
      weeks at the start of the cultivation when intensive assaying and monitoring
      should be carried out. After this period, the medium flow rate and MCA production
      rate may be predicted by linear extrapolation.

PMID- 1367812
TI  - Influence of lactate, ammonia, and osmotic stress on adherent and suspension BHK
      cells.
AB  - Adherent and suspension Baby Hamster Kidney (BHK) 21c13 cells were cultivated in
      a 2.5-1 stirred-tank reactor with indirect aeration. Cell concentration and
      viability as well as glucose, lactate, ammonia, and protein concentrations in the
      medium and intracellular and extracellular activities of the intracellular
      enzymes were determined off-line. The concentrations of glucose, lactate,
      ammonia, and the activity of lactate dehydrogenase in the culture medium were
      monitored on-line. The cell/cell fragment size distribution was determined by
      laser flow cytometer off-line. In several runs, the size distributions were
      ascertained on-line by a laser flow cytometer. The influence of lactate, ammonia,
      and osmotic pressure on the viability and biological parameters of the suspension
      cells was evaluated. In Roux flasks, lactate and ammonia had considerable
      influence on the cell properties; in stirred tank reactors, these influences were
      negligible up to 9.5 g l-1 lactate and 150 mg l-1 NH+4 ion concentrations. The
      influence of high osmolarity on the biological parameters of the cells was much
      less in the stirred-tank than in the Roux flasks. The adhesion of adherent cells
      on a surface was impeded neither by the lactate (up to 6 g l-1) nor by the
      ammonia concentration (up to 150 mg l-1). However, with increasing osmolarity,
      the fraction of the cells adhered to a surface reduced to below 5% (at 680 mOsmol
      l-1).

PMID- 1367813
TI  - Heat shock gene expression in continuous cultures of Escherichia coli.
AB  - Temperature inducible systems for the controlled expression of recombinant genes
      are finding increasing industrial applications. These involve either short or
      long term exposure of the process culture to superoptimum temperatures. It is
      well known that bacteria respond to a sudden increase in their environmental
      temperature with an immediate transient increase in the synthesis rates of
      specific heat shock proteins. The use of continuous flow processes for the
      production of recombinant proteins would allow higher productivity and smaller
      scale bioreactors. However, the induction patterns of heat shock proteins in
      continuous culture after defined heat shocks are not well defined despite a large
      amount of information which is now available concerning heat shock protein
      induction in batch cultures. An overview of this information is presented to
      enable a better understanding of the response in continuous cultures. The latter
      was investigated by monitoring the transient expression of a representative heat
      shock gene, htpG, in E. coli in continuous culture. The relative magnitude of the
      response was found to be both temperature and exposure time dependent, but growth
      rate independent. Changing medium composition resulted in both different steady
      and transient state expression levels.

PMID- 1367814
TI  - Animal cell culture processes--batch or continuous?

PMID- 1367815
TI  - Fundamental bottlenecks in the application of continuous bioprocesses.
AB  - Continuous culture is applied mainly as a research tool and much less as a
      production process. Fundamental bottlenecks in continuous culture are discussed
      to help shed light on this apparent contradiction. Based on a discussion of
      technical, process related, and economic/market bottlenecks it is concluded that
      the often mentioned productivity argument in favor of continuous processing is
      much too simple. The optimal choice of a process mode is determined by a full
      understanding of the equipment and production plant factors and of the
      economic/market factors. Very often the resulting choice will be the fed batch
      and/or the cell retention process mode which is characterized by low growth
      rates. Therefore more research towards product formation at low growth rates
      (less than 0.05 h-1) is needed.

PMID- 1367816
TI  - Continuous hybridoma suspension cultures with and without cell retention:
      kinetics of growth, metabolism and product formation.
AB  - A laboratory scale bioreactor was constructed from glass and polycarbonate
      materials whereby a track-etch membrane (3 microns pore diameter) was integrated
      into its two-part bottom flange. The reactor performance was evaluated for
      continuous hybridoma suspension cultures under various conditions of cell
      retention. A total retention experiment demonstrated that this type of stirred
      tank reactor cannot be operated at near zero growth rate conditions. Instead, at
      steady viable cell concentrations of congruent to 3 x 10(6) cells per ml,
      specific growth and death rates were estimated at 0.60 +/- 0.06 d-1. Specific
      substrate (glucose, glutamine, O2, amino acids) consumption, by-product (ammonia,
      alanine, amino acids) and product (antibody) production rates as well as various
      apparent molar yield coefficients were obtained and are compared to metabolic
      quotients and yield coefficients previously calculated from standard continuous
      culture experiments, i.e., without cell retention, at specific growth rates of
      0.63 and 1.24 d-1. Furthermore, steady-state data on viable cell and antibody
      concentrations, spec. mAb productivities, and space-time yields determined before
      and after a step change (2.5-fold increase) in dilution rate at identical
      specific growth rates mu are presented.

PMID- 1367817
TI  - Effect of specific growth rates on productivity in continuous open and partial
      cell retention animal cell bioreactors.
AB  - A clonal derivative of a transfectant of the SP2/0 myeloma cell line producing a
      chimeric monoclonal antibody was cultivated in both continuous open and
      continuous partially-closed bioreactors. Using an open system for the
      determination of kinetic parameters, we showed that the production of this
      chimeric mAb was growth associated. As such, the volumetric productivity
      increased linearly with increasing dilution rate up to the maximum dilution rate.
      Three continuous cultivations employing partial cell retention were conducted. In
      agreement with mathematical predictions, the product titer and volumetric
      productivity were independent of the degree of cell retention when the total
      dilution was held constant. When cells were maintained at a low specific growth
      rate, the product titer was independent of dilution rate and the volumetric
      productivity increased with increasing dilution rate, again in agreement with
      mathematical predictions. Since the partially-closed bioreactor could be operated
      at dilution rates in excess of the maximum specific cellular growth rate,
      volumetric productivities were greater than those achievable in the open
      bioreactor. However, when cells were maintained at a high specific growth rate,
      cell accumulation was limited and product titers decreased at high dilution
      rates. Therefore, the volumetric productivity in this latter case did not
      increase at higher dilution rates.

PMID- 1367818
TI  - Safety and economic aspects of continuous mammalian cell culture.
AB  - Mammalian cell cultures are the most appropriate host cells for recombinant DNA
      derived products if complex protein structures have to be synthesized in their
      native form. Due to their physiological behaviour they grow either adherent or in
      suspension. For the attachment of adherent cells, microcarriers or wire springs
      can be applied to increase the internal surface of the bioreactor. Both systems
      provide a simplified media exchange but, however, show some limitations in scale
      up. In contrast, suspension culture systems as homogeneous systems independent of
      any carrier have not shown any limitation in scale up. Because most cell lines
      which are of commercial interest grow in suspension, this technology is best
      advanced and used in batch and continuous mode. Although mammalian cell cultures
      are sensitive to hydrodynamic shear forces, technologies for deep tank production
      are developed which allow stirrer tip speed of up to 1.5 m s-1 sufficient for
      oxygen uptake, suspension of cells and homogeneous supply with nutrients. For
      long term bioprocesses without selection pressure it has to be considered that
      transformed cell lines might show genetic instability due to their variations of
      chromosomes. In addition, sterile technology becomes an important factor in long
      term bioprocesses. The decision as to which cell culture system should be chosen,
      whether batch or continuous processes should be applied essentially is based on
      the capital investment, the amount of material to be produced, genetic stability
      of the production cell line, reliability of sterile technology and the
      flexibility required in the production plant. Under the assumption that 20 kg of
      a protein have to be produced per year and the same product concentrations in the
      harvest fluid are reached in the batch process and for instance in the chemostat,
      it can be considered that the capital investment for one 10,000 l batch process
      and a 2 x 2,000 l continuous process, necessary to produce the amount of
      material, is comparable. Risk of microbial contamination or technical failure can
      be considered to be fairly low in the batch process. The economic risk for long
      term bioprocess in the chemostat can be expected to be medium and high in the
      perfusion system which is in the large scale not technically fully satisfactory.
      In addition, due to the longer down time period after contaminations and the
      start up of the continuous process, the annual yield of the batch process can be
      considered to be higher.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1367819
TI  - Chemostat cultures of yeasts, continuous culture fundamentals and simple
      unstructured mathematical models.
AB  - Fundamental aspects of chemostat cultures are reviewed. Using yeast cultures as
      examples, it is shown that steady states in chemostats may be predicted
      quantitatively by combining the correct number of unstructured kinetic models
      with expressions for existing stoichiometric constraints. The necessary number of
      such kinetic models corresponds to the number of limiting substrates and
      increases with the number of different metabolic pathways available to the
      strain. This is demonstrated by an experimental comparison of yeast growth
      limited by glucose alone for which metabolism is oxidative, and growth doubly
      limited by both glucose and oxygen, which occurs according to an oxido-reductive
      metabolism. The steady state data for such experiments can in principle be
      predicted based on a minimal amount of information by a simple stoichiometric
      model. It represents the overall stoichiometry of growth by a superposition of a
      fully oxidative and a fully reductive growth reaction and uses the concept of
      "aerobicity" to characterize the relative importance of the two reactions.

PMID- 1367820
TI  - Simulation of batch and continuous reactors with co-immobilized yeast and beta
      galactosidase.
AB  - A reaction-diffusion model was used to simulate a co-immobilized system utilizing
      the numerical method of orthogonal collocation. The production of ethanol from
      deproteinized whey using beta-galactosidase co-immobilized with Saccharomyces
      cerevisiae in calcium alginate gel beads was chosen as a model system. Calculated
      concentrations of lactose, glucose, galactose and ethanol were compared with
      experimental data for a batch reactor and a continuous horizontal packed-bed
      reactor. The mathematical model has been used to analyse the influence of
      internal and external mass transfer for the continuous reactor. The external mass
      transfer was shown to be of minor importance. The introduction of baffles
      decreased the backmixing in the horizontal packed-bed reactor. Internal mass
      transfer was found to be the main cause of the reduction in the apparent reaction
      rate. Thus, much of the expected increase in reaction rate is diminished by mass
      transfer hindrance when the cell concentration is increased.

PMID- 1367821
TI  - Design considerations for an immobilized cell bioreactor operating in a batch
      recirculation mode.
AB  - Immobilizing microbial cells and enzymes used in biological and biochemical
      processes is advantageous and has been a subject of intensive study in recent
      years. Successful implementation of this technology requires complete
      understanding of physical, chemical and biological parameters which influence the
      performance of such a system. This paper focuses on a few basic design
      considerations which are essential to the design and operation of immobilized
      cell bioreactors. A process using microorganisms entrapped in calcium alginate
      gel as a biocatalyst is considered. This system is used to biodegrade the organic
      compound, phenol. A batch reactor operated in a recirculation mode is used, and
      parameters like concentration of dissolved oxygen, concentration of the organic
      compound, bead size, biomass loading and the flow rate are studied. The
      bioreactor can be operated within many operating windows where one of the above
      parameters may be rate limiting. With the help of conceptual and experimental
      data, the influence of the above parameters on the reaction rates is discussed.

PMID- 1367822
TI  - Large-scale insect cell culture: methods, applications and products.
AB  - The primary development in large-scale insect cell culture over the past year has
      been the continuing accumulation of documented evidence (fundamental and applied)
      that conventional aerated stirred-tank and air-lift bioreactors may be employed
      for insect cell cultivation and recombinant protein production, provided that air
      sparging, agitation, and the addition to the medium of Pluronic F-68 and methyl
      cellulose polymers are carefully controlled.

PMID- 1367823
TI  - Large-scale plant cell culture: methods, applications and products.
AB  - Recent significant contributions to the design of large-scale plant cell cultures
      for secondary metabolite production include: the development of a strategy to
      control the concentration of dissolved gases at constant shear; a surface
      immobilization technique to retain cell mass at high mixing rates; and a modified
      stirred-tank reactor with a mesh cage to prevent damage of hairy root cultures.

PMID- 1367824
TI  - Large-scale mammalian cell culture: methods, applications and products.
AB  - Animal cell cultures are used to generate products of enormous biotechnological
      value. These systems rely on conventional manufacturing techniques using
      organisms that are the result of either cell fusions or genetic engineering. A
      wealth of new techniques has allowed improvements and developments to be made in
      culture medium composition, cell modification, and bioreactor design and
      operation. This progress is expected to be commercially exploited as new products
      reach the market place.

PMID- 1367825
TI  - High-cell-density cultivation of Escherichia coli.
AB  - High-cell-density cultivations of Escherichia coli in glucose-mineral-salt media
      produce more than 100 g dry cells litre-1 in special fed-batch modes with feeding
      of glucose and ammonia only. The specific growth rate can be adjusted to allow
      optimum recombinant protein generation.

PMID- 1367826
TI  - New materials and technology for cell immobilization.
AB  - The choice of support materials for immobilizing cells is rapidly expanding. The
      literature that has appeared over the past year suggests that hydrogels will
      remain the first choice for the forseeable future, even though they are
      associated with many widely recognized problems. There is increasing interest in
      the use of tougher polymeric materials, and especially of inorganic ceramic
      supports. However, the most suitable cell support can be selected only after the
      process or form of reactor in which it is to be used has been assessed.

PMID- 1367827
TI  - Catalytic antibodies and biomimetics.
AB  - Of the various approaches being studied to mimic the catalytic properties of
      enzymes, catalytic antibody research is advancing most rapidly and successfully;
      the discovery of new reactions and new catalytic antibody-producing haptenic
      structures continues unabated. One of the highlights of the past year was the
      design and synthesis of a catalytically active peptide. The overall area of
      catalytic antibodies and biomimetics will be prominent in future biotechnological
      applications, as further advances are made and the nature of the catalyzed
      reactions becomes better understood.

PMID- 1367828
TI  - Non-aqueous enzymology.
AB  - Compelling evidence has been obtained during the past year that enzymes retain
      their native active-site structure in organic solvents, and yet the properties of
      the solvent significantly affect enzyme kinetics. Fundamental advances in
      enzymatic catalysis in monophasic organic media are discussed and selected
      applications in the areas of asymmetric, polymer and chemoenzymatic syntheses are
      highlighted.

PMID- 1367829
TI  - Integrated product formation and recovery.
AB  - As continues to be demonstrated, the in situ recovery of selected products froma
      bioreactor can have a significant positive impact on production. The strategies
      that are focused on here are: aqueous two-phase biocatalysis; non-aqueous
      biocatalysis; and membrane-enhanced biocatalysis. Additional fundamental
      understanding of molecular partitioning and biocatalytic activity in these
      environments will facilitate the rational selection of the components involved in
      these processing strategies.

PMID- 1367830
TI  - New methods for separation and recovery of biomolecules.
AB  - New methods and applications in the separation of biomolecules are reviewed, with
      an emphasis on the large-scale recovery of proteins. Highlights include the
      advent of flow-through particles in perfusion chromatography, which allows for
      very high flow rates, while retaining a high chromatographic efficiency.

PMID- 1367831
TI  - Biodegradation of toxic and environmental pollutants.
AB  - Organic chemicals that are toxic to humans and to the environment can be
      transformed and metabolized by a variety of microorganisms. Such chemicals
      include trichloroethylene, chloroform, carbon tetrachloride, toluene, phenols,
      chlorinated phenols, polychlorinated biphenyls and polyaromatic hydrocarbons.
      This review focuses on some of the most important recent developments in the
      biodegradation of these toxic chemicals. Depending on the compound and the
      organism, the extent of our understanding ranges from the molecular level to the
      conceptual.

PMID- 1367832
TI  - Bioremediation of groundwater pollution.
AB  - Significant progress has been made in the past year towards an understanding of
      the microbial processes in subsurface environments that may allow natural
      microbial populations to be employed for bioremediation of groundwater pollution.
      Among the highlights were: the discovery of several previously unknown xenobiotic
      degrading abilities in groundwater microorganisms; progress in using the unique
      abilities of methanotrophs to oxidize halogenated solvents; and characterizations
      of microbial populations from subsurface soils.

PMID- 1367833
TI  - Biological control of wild animal infections.
AB  - Until recently, there were few examples of biological control of wild animal
      infections. The most significant development in this field is the use of a
      vaccinia--rabies recombinant virus or other recombinants for the control of
      rabies by oral vaccination of vectors, both in Europe and in North America.

PMID- 1367834
TI  - Risk assessment in environmental biotechnology.
AB  - Scientists in academia and industry concur that appropriate oversight and
      regulation for biotechnology are in the best interests of society. Field trials
      have not resulted in any uncontrolled hazard. Oversight should continue and
      useful methods for assessing risk associated with release of genetically
      engineered organisms to the environment have been proposed.

PMID- 1367835
TI  - Biochemical engineering.

PMID- 1367836
TI  - Environmental biotechnology.

PMID- 1367837
TI  - Isolation and partial amino acid sequence of domains of nitrate reductase from
      spinach.
AB  - Fragments of spinach nitrate reductase (NR) were prepared by limited proteolysis
      of immunopurified enzyme using both Staphylococcus aureus V8 protease and
      trypsin. Incubation of NR with V8 protease yielded two enzymically active
      fragments which could be size separated by FPLC on a Superose 12 column or
      subjected to further proteolysis while bound to a blue Sepharose affinity column.
      An NADH-ferricyanide (NADH-FR) active fragment bound to, and was eluted from, a
      blue Sepharose column by micromolar concentrations of NADH. A fragment with
      methyl viologen-NR activity was either eluted from the same column using 1 M KNO3
      or on further treatment in situ on the blue Sepharose column with trypsin.
      Incubation of holo-NR with trypsin resulted in the loss of all terminal nitrate
      reducing activities but no loss in either NADH-FR activity or NADH-cytochrome c
      reductase activity. Two protease-sensitive regions of NR are shown which connect
      essentially between the flavin (FAD) and haem domains, and between the haem and
      molybdenum domains of NR. Amino acid analysis of the FAD- and FAD/haem-containing
      domains yielded two partial sequences which are compared with sequences deduced
      from complementary DNA (cDNA) of NR from Arabidopsis, tobacco and spinach. The
      deduced sequences from Arabidopsis and tobacco are found to be ca 80% and the
      spinach 100% homologous to the sequence obtained for spinach NR fragments.

PMID- 1367838
TI  - Triterpenes from Mucuna birdwoodiana.
AB  - Methanolic extracts of the stalks of Mucuna birdwoodiana on acid hydrolysis and
      subsequent methylation with diazomethane provided four triterpene sapogenols. On
      the other hand, investigation of glycosides after methylation of the same extract
      led to the isolation of four triterpene glycosides. On the basis of chemical and
      spectral evidence, their structures were characterized as methyl asiatate, methyl
      maslinate, two new sapogenols, methyl 1 beta,2 alpha,3 beta,23-tetrahydroxyolean
      12-en 28-oate (mucunagenin a), its urs-12-en isomer (mucunagenin b), 3-O-(6-O
      methyl-beta-D-glucuronopyranosyl) methyl asiatate 3-O-[alpha-L-arabinopyranosyl(1
      ---2)]-6-O-methyl-beta-D-glucur onopyranosyl methyl maslinate, 3-O-[alpha-L
      arabinopyranosyl(1----2)]-6-O-methyl-beta-D-glucur onopyranosyl methyl asiatate
      and 3-O-(6-O-methyl-beta-D-glucuronopyranosyl) asiatic acid 28-O-beta-D
      glucopyranoside.

PMID- 1367839
TI  - A bidesmosidic triterpenoid saponin from Schefflera octophylla.
AB  - A new 3,28-bidesmosidic triterpenoid saponin was isolated from the leaves of
      Schefflera octophylla together with a new trisaccharide and oleanonic acid. Based
      on spectroscopic data and chemical transformations, the structures of the new
      constituents were determined as 3-epi-betulinic acid 3-O-beta-D-glucopyranoside
      28-O-[alpha-L-rhamnopyranosyl(1----4)-O-beta-D-glucopyranosyl(1----6)]-b eta- D
      glucopyranoside and alpha-L-rhamnopyranosyl(1----4)-O-beta-D-glucopyranosyl(1---
      6)-beta-D- glucopyranose.

PMID- 1367840
TI  - Steroidal saponins from the bulbs of Camassia cusickii.
AB  - Six new steroidal saponins have been isolated from the fresh bulbs of Camassia
      cusickii. Their structures were determined by spectroscopic analysis and some
      chemical transformations to be (25R)-5 alpha-spirostan-3 beta,6 alpha-diol
      (chlorogenin) 6-O-beta-D-glucopyranoside, chlorogenin 6-O-beta-D-glucopyranosyl
      (1----2)-beta-D-glucopyranoside, chlorogenin 6-O-beta-D-glucopyranosyl-(1----3)
      beta-D-glucopyranoside, chlorogenin 6-O-beta-D-glucopyranosyl-(1----2)-O-[beta-D
      glucopyranosyl-(1----3)]-beta- D-glucopyranoside, (25R)-6 alpha-hydroxy-5 alpha
      spirostan-3-one 6-O-beta-D-glucopyranosyl- (1----3)-beta-D-glucopyranoside and
      (25R)-3,3-dimethoxy-5 alpha-spirostan-6 alpha-ol 6-O-beta-D-glucopyranosyl-(1---
      3)-beta-D-glucopyranoside. The saponins isolated were shown to contribute to the
      bitter taste of the bulbs.

PMID- 1367841
TI  - Phenylpropanoid and iridoid glycosides from Pedicularis spicata.
AB  - One new phenylpropanoid glycoside, pedicularioside H, and five known glycosides,
      gardoside methyl ester, shanzhiside methyl ester, 5-deoxypulchelloside I,
      verbascoside and pedicularioside A, were isolated from whole plants of
      Pedicularis spicata. On the basis of the spectral data, chemical evidence and
      comparison with authentic samples, pedicularioside H was determined to be 1'-O
      beta-D-(3-methoxy-4-hydroxy-beta-phenyl)-ethyl-4'-O-feruloyl- beta-D- apiosyl(1--
      -3')-alpha-L-rhamnosyl-(1----6')-glucopyranoside .

PMID- 1367842
TI  - Flavonoids of Ochradenus baccatus.
AB  - From the aerial parts of Ochradenus baccatus, the new flavonoids, quercetin 3-O
      beta-glucosyl(1----2)-alpha-rhamnoside-7-O-alpha-rhamnoside and quercetin 3-O-p
      coumaryl(1----6)-beta-glucosyl(1----6)-beta-glucoside-7-O-alpha rhamnoside were
      isolated. The known quercetin glycosides, quercetin 3-gentiobioside,
      isoquercitrin, quercitrin, together with the known kaempferol glycosides,
      astragalin and afzelin, were also characterized. The structures were established
      by conventional methods of analysis and confirmed by spectral analysis.

PMID- 1367843
TI  - Flavonol glycosides from Monnina sylvatica.
AB  - A new kaempferol triglycoside and three known kaempferol glycosides, among them
      two apiosides, have been isolated from the aerial parts of Monnina sylvatica. The
      structures were established on the basis of acid and enzymatic hydrolysis and
      spectral data (UV, 1H and 13CNMR, NOE difference measurements, D/CI and FAB-MS)
      of the isolates and of some derivatives. The triglycoside kaempferol 3-O-beta-D
      glucosyl-(1----2)-O-[alpha-L-rhamnosyl(1----6)]-beta-D- galactoside is a new
      natural product. The configuration of the apiosyl moiety in kaempferol 3-O-beta-D
      apiosyl(1----2)-beta-D-galactoside and kaempferol 3-O-beta-D-apiosyl(1----2)-O
      [alpha-L-rhamnosyl(1----6)]- beta-D-galactoside was established through NOE
      difference measurements on the peracetate.

PMID- 1367844
TI  - Both bane and blessing--inclusion bodies.

PMID- 1367845
TI  - Undercooling--low temperature without freezing.

PMID- 1367846
TI  - Bispecific antibodies for targeted cellular cytotoxicity.
AB  - Bispecific antibodies have the ability to redirect normal cytotoxic mechanisms to
      kill tumors or pathogens and thus represent a potentially powerful tool for the
      therapy of cancer and infectious disease.

PMID- 1367847
TI  - The molecular basis of partitioning in aqueous two-phase systems.
AB  - Protein purification based on partition in aqueous two-phase systems has
      attracted interest for many years. This approach has been advocated as a primary
      stage unit operation in downstream processing. In reality, application has been
      strictly limited through inadequate understanding of the complex molecular forces
      involved in partitioning processes.

PMID- 1367848
TI  - Malaria vaccines--progress and problems.
AB  - Developing a vaccine against malaria is a major priority of the WHO. A decade of
      research exploiting the techniques of molecular biology has yielded a series of
      potentially protective vaccines. However, progress has been frustrated by the
      complexity of the parasite's life cycle and the antigenic diversity exhibited by
      each stage. Although candidate vaccines are now entering human trials, questions
      still arise concerning the nature of a successful malaria vaccine and who will
      benefit from it.

PMID- 1367849
TI  - Tailoring the microenvironment of enzymes in water-poor systems.
AB  - Biocatalytic systems using enzymes in organic solvents open up the possibility of
      performing a whole range of reactions which would not normally occur under
      physiological conditions. The ability to perform reverse hydrolysis, or to
      convert substances relatively insoluble in aqueous environments on a scale of
      practical value in commercial applications are among those reactions for which
      water-poor systems are appropriate.

PMID- 1367850
TI  - Mammalian recombinant proteins: vectors and expression systems.

PMID- 1367851
TI  - Mammalian recombinant proteins: structure, function and immunological analysis.

PMID- 1367852
TI  - Control of gene expression: tissue-specific expression.

PMID- 1367853
TI  - Human DNA polymorphisms and methods of analysis.
AB  - The current predominant method of analyzing base substitution polymorphisms, RFLP
      analysis, is likely to be gradually supplanted by methods based on PCR because of
      the improved sensitivity and genotyping rate. The most promising PCR methods for
      analysis appear to be allele-specific PCR and single-stranded conformational
      analysis. The single-stranded conformation approach has already been applied to
      the scanning of cystic fibrosis exons for new mutations. Linkage mapping projects
      that cover large segments of the human genome will probably rely, in the coming
      years, primarily on tandem repeat polymorphisms, particularly microsatellite
      polymorphisms. Microsatellite polymorphisms have at least a fourfold advantage
      over base substitution RFLPs because they are twice as informative and can be
      typed at at least twice the rate. The facioscapulohumeral muscular dystrophy gene
      was recently mapped in just 6 weeks using microsatellite polymorphisms. Because
      of the informativeness handicap, it will be difficult for base substitution
      polymorphisms to overtake tandem repeat markers for large-scale linkage mapping.
      Methods that allow base substitution polymorphisms to be typed at two or three
      times the rate of microsatellite markers would have to be developed. Most of the
      other applications of DNA polymorphisms described in the introduction are also
      increasingly likely to rely on highly informative tandem repeat markers in the
      future. Methods for analysis will probably be based on PCR. It is easy to
      envisage, for example, an automated method for large-scale DNA fingerprinting of
      individuals based upon a standard set of highly informative, dependable
      microsatellite polymorphisms. Methods for analyzing base substitution
      polymorphisms will continue to be important for the diagnostic detection of
      disease-gene alleles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1367854
TI  - Gene mapping.

PMID- 1367855
TI  - The molecular basis of genetic disease.
AB  - The pace of localization and characterization of genes affected in human genetic
      disorders is quickening. Many important genes were localized or characterized
      recently: genes for in cystic fibrosis, NF-2, Marfan's syndrome and xeroderma
      pigmentosum, to name a few. Also, in the past 15 months, the CFTR gene affected
      in cystic fibrosis has been isolated, the first disease gene to be isolated
      without use of previous cytogenetic clues, such as deletions or translocations in
      sporadic cases. Other examples should follow, although we have been disappointed
      to date by the difficulties encountered in the isolation of Huntington's disease
      gene which was localized a number of years ago to distal chromosome 4p. It is
      still very difficult to isolate a disease gene without critical cytogenetic
      information. New improved techniques for finding the desired expressed sequences
      in a large cloned segment of human DNA are needed. Our ability to find mutant
      alleles of a given sequence has expanded greatly with the recent technical
      advances in denaturing gradient gel electrophoresis, chemical cleavage, and
      single-stranded conformational electrophoresis. One would predict that
      information derived from the human genome project will have a major impact upon
      the isolation of further disease genes. As whole regions of human chromosomes or
      indeed entire chromosomes are physically mapped and cloned as continuous,
      overlapping YACs (yeast artificial chromosomes), isolation of disease genes will
      become easier and easier.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1367856
TI  - Genetic abnormalities in cancer.

PMID- 1367858
TI  - Mammalian gene studies.

PMID- 1367857
TI  - Gene therapy.

PMID- 1367860
TI  - Natural products of commercial potential as medicines.
AB  - Recent advances in research on natural products (of both low and high molecular
      weight) of plant origin and their commercial potential as medicines are
      discussed. Substances with immunomodulating, antiviral, antimicrobial,
      antiparasite, antitumor, anti-inflammatory, hypoglycemic, tranquillizer and
      antifeedant activities are focused on.

PMID- 1367859
TI  - Biochemical and molecular studies of symbiotic nitrogen fixation.

PMID- 1367861
TI  - Vaccines.
AB  - Much progress has been made towards reaching an understanding of immune responses
      at the molecular level. This has provided much needed information for identifying
      the antigens which will afford protection against diseases such as rabies,
      malaria, whooping cough, hepatitis and acquired immune deficiency syndrome, and
      for presenting them to the immune system.

PMID- 1367862
TI  - Thrombolytic therapy with tissue-type plasminogen activator: new modes and novel
      variant plasminogen activators.
AB  - Tissue-type plasminogen activator produced by recombinant DNA technology, has
      been established as an important thrombolytic agent in the treatment of acute
      myocardial infarction. New approaches to increase the effectiveness of this
      agent, including rapid high dose administration are being investigated. Several
      novel protein engineered variant forms of plasminogen activators have been
      produced that have increased thrombolytic potency in animal models and offer the
      potential of a more effective lower dose agent than can be administered
      clinically as a single bolus intravenous injection.

PMID- 1367863
TI  - Colony-stimulating factors and cytokine receptor network.
AB  - Cytokines play a vital role in coordinating immune and inflammatory responses. As
      many cytokine gene hunters have begun to focus their efforts on receptors, novel
      aspects of hemopoietic growth factor receptors have emerged. Two types of growth
      factor receptors have been classified--the cytokine receptor family and growth
      factor receptor family with tyrosine kinase activity. The two types of receptors
      may have unique roles in 'inducible' and 'constitutive' hemopoiesis which are
      controlled by immunological stimuli and by interaction with stromal cells,
      respectively.

PMID- 1367864
TI  - Antibody engineering.
AB  - Antibody engineering has received a boost from the development of an Escherichia
      coli expression system that now allows the screening of libraries with bacteria
      or phages. These random selection techniques can be applied using knowledge
      obtained from new X-ray structures of recombinant antibody domains, and anti
      peptide antibodies. The first crystal structure of an anti-idiotype complex has
      also been solved. Additionally, the engineering of binding sites for metals and
      haptens, and the design of new immunotoxins have been reported.

PMID- 1367865
TI  - Drug delivery.
AB  - Methods for the delivery of the products of biotechnology, namely peptides and
      proteins, are reviewed. More efficient methods of parenteral administration
      include the incorporation of drugs in liposomes, whereas the system favoured for
      respiratory delivery is the nasal route. The improved oral delivery of
      polypeptides remains an elusive goal.

PMID- 1367866
TI  - Antisense technology.
AB  - During the past 12 months, significant advances have been reported in the
      medicinal chemistry, and the pharmacodynamic and pharmacokinetic characterization
      of oligonucleotides. Advances in medicinal chemistry suggest that the scope for
      additional modifications as a means of developing therapeutic agents is
      substantial. This is confirmed by our clearer understanding of the
      pharmacodynamic and pharmacokinetic properties of oligonucleotides and the
      increasing number of molecular targets against which they have been shown to be
      active.

PMID- 1367867
TI  - Plant biotechnology.

PMID- 1367868
TI  - Pharmaceutical applications.

PMID- 1367870
TI  - Microchip implant for positive animal identification.

PMID- 1367869
TI  - Choosing an appropriate agarose for separation and purification of PCR products.

PMID- 1367872
TI  - Simultaneous phase contrast and fluorescence microscopy.

PMID- 1367871
TI  - Capillary non-gel sieving electrophoresis of nucleic acids.

PMID- 1367873
TI  - Are media just media? (Part III).

PMID- 1367874
TI  - A validatable membrane-based system for the removal of viruses from
      biopharmaceuticals.

PMID- 1367875
TI  - Saponins from Albizzia lucida.
AB  - Three main saponins were isolated from the seeds of Albizzia lucida. Their
      structures were established by spectral analyses and chemical and enzymatic
      transformations as 3-O-[beta-D-xylopyranosyl(1----2)-alpha-L-arabinopyranosyl (1-
      --6)] [beta-D-glucopyranosyl (1----2)] beta-D-glucopyranosyl echinocystic acid; 3
      O-[alpha-L-arabinopyranosyl (1----6)] [beta-D-glucopyranosyl (1----2)]-beta-D
      glucopyranosyl echinocystic acid and 3-O-[beta-D-xylopyranosyl (1----2)-beta-D
      fucopyranosyl (1----6)-2-acetamido-2-deoxy-beta-D-glucopyranosyl echinocystic
      acid, characterized as its methyl ester.

PMID- 1367876
TI  - Cyanidin 3-[6-(p-coumaroyl)-2-(xylosyl)-glucoside]-5-glucoside and other
      anthocyanins from fruits of Sambucus canadensis.
AB  - From the fruits of Sambucus canadensis four anthocyanin glycosides have been
      isolated by successive application of an ion-exchange resin, droplet-counter
      chromatography and gel filtration. The structure of the novel, major (69.8%)
      pigment, cyanidin 3-O-[6-O-(E-p-coumaroyl-2-O-(beta-D-xylopyranosyl)-beta-D-
      glucopyranoside]-5-O-beta-D-glucopyranoside, was determined by means of chemical
      degradation, chromatography and spectroscopy, especially homo- and heteronuclear
      two-dimensional NMR techniques. The other anthocyanins were identified as
      cyanidin 3-sambubioside-5-glucoside (22.7%), cyanidin 3-sambubioside (2.3%) and
      cyanidin 3-glucoside (2.1%).

PMID- 1367877
TI  - A triterpenoid and its saponin from Phytolacca esculenta.
AB  - A new triterpenoid, esculentagenin, and its glycoside, esculentoside M, were
      isolated from the roots of Phytolacca esculenta and characterized as 11-oxo-3-O
      methyloleanata-12-en-2 beta,3 beta,23-trihydroxy-28-oic acid and 3-O-[beta-D
      glucopyranosyl(1----4)-beta-D-xylopyranosyl]-28-O-beta-D- glucopyranosyl-11-oxo
      30-methyloleanate-12-en-2 beta,3 beta,23-trihydroxy-28-oic acid by spectral and
      chemical evidence.

PMID- 1367878
TI  - Leucasin, a triterpene saponin from Leucas nutans.
AB  - A new saponin, leucasin, has been isolated from Leucas nutans and characterized
      on the basis of chemical investigation and spectroscopic studies as 3-O-[beta-D
      glucopyranosyl(1----2)beta-D-glucopyranosyl]2 alpha, 3 beta-dihydroxylup-20(29)
      ene. Lupeol palmitate, sitosterol and stigmasterol were also isolated.

PMID- 1367879
TI  - A spirostane hexaglycoside from Agave cantala fruits.
AB  - A new steroidal glycoside, agaveside D, isolated from the fruits of Agave cantala
      was characterized as 3 beta-(alpha-L-rhamnopyranosyl-(1----2),beta-D
      glycopyranosyl- (1----3)-beta-D-glucopyranosyl[beta-D-xylopyransoyl-(1----4)
      alpha -L-rhamnopyranosyl-(1----2)]-beta-D-glucopyranosyl)-25R-5 alpha-spirostane
      on the basis of chemical degradation and spectrometry.

PMID- 1367880
TI  - Triterpenoids and their glycosides from the bark of Schefflera octophylla.
AB  - A new triterpene and its glycosides were isolated from the bark of Schefflera
      octophylla together with asiatic acid and asiaticoside. Based on spectroscopic
      data, especially 2DNMR, and chemical transformations the structures of the new
      compounds were determined as 3 alpha-hydroxy-urs-12-ene-23,28-dioic acid and 3
      alpha-hydroxy-urs-12-ene-23,28-dioic acid 28-O-[alpha-L-rhamnopyranosyl (1----4)
      O-beta-D-glucopyranosyl (1----6)]-beta-D-glucopyranoside. For the first time
      asiaticoside was isolated from a plant other than Centella asiatica.

PMID- 1367881
TI  - Phenylpropanoid and iridoid glycosides from Pedicularis lasiophrys.
AB  - Two new compounds, pedicularioside E and F, were isolated from whole plants of
      Pedicularis lasiophrys, along with the four known compounds, verbascoside,
      cistanoside C, cistanoside D and 8-epiloganin. On the basis of spectral and
      chemical evidence, pedicularioside E and F were identified to be 1'-O-beta-D-(3
      methoxy-4-hydroxy-beta-phenyl)-ethyl-6'-O-feruloyl- alpha-L-(2-acetyl)-rhamnosyl
      (1----3')-4'-acetylglucopyranoside and shanzhisin methyl ester cellobioside,
      respectively.

PMID- 1367882
TI  - Acylated pelargonidin glycosides in the red-purple flowers of Pharbitis nil.
AB  - Four acylated pelargonidin glycosides and pelargonidin 3-sophoroside-5-glucoside
      were isolated from 23 red-purple cultivars of Pharbitis nil. The acylated
      anthocyanins were all based on pelargonidin 3-sophoroside-5-glucoside and were
      identified as the 3-O-[2-O-(beta-D-glucopyranosyl)-6-O-(trans-caffeyl)-beta-D-
      glucopyranoside]-5-O-(beta-D-glucopyranoside), the 3-O-[2-O-(6-O-(trans-3-O-(beta
      D-glucopyranosyl)caffeyl)-beta- D-glucopyranosyl)-beta-D-glucopyranoside]-5-O
      (beta-D-glucopyranoside), the 3-O-[2-O-(6-O-(trans-3-O-(beta-D
      glucopyranosyl)caffeyl)-beta- D-glucopyranosyl)-6-O-(trans-caffeyl)-beta-D
      glucopyranoside]-5-O-(beta- D-glucopyranoside); and the 3-O-[2-O-(6-O-(trans-3-O
      (beta-D-glucopyranosyl)caffeyl)-beta-D- glucopyranosyl)-6-O-(trans-4-O-(6-O
      (trans-3-O-(beta-D- glucopyranosyl)caffeyl)- beta-D-glucopyranosyl)caffeyl)-beta
      D-glucopyranoside]-5-O-(beta-D- glucopyranoside). By the analysis of these
      anthocyanin constituents variously in 23 cultivars, it was found that the red
      flower colour gradually changed into more bluish colour with increasing numbers
      of caffeic acid residues in the acylated pelargonidin glycosides. The stabilities
      of these anthocyanins increased in the order of increasing caffeyl substitution.

PMID- 1367883
TI  - Two flavonol glycosides from Vancouveria hexandra.
AB  - In addition to two known glycosides, ikarisoside F and epimedin A, two new
      glycosides of a flavonol with a gamma, gamma-dimethylallyl group were isolated
      from the underground and the aerial parts of Vancouveria hexandra. The structures
      were determined to be des-O-methylanhydroicaritin 3,7-diglucoside and
      anhydroicaritin 3-glucosyl (1----3)rhamnoside-7-glucoside by means of spectral
      analysis.

PMID- 1367884
TI  - Four flavonol glycosides from Achlys triphylla.
AB  - Four new flavonol glycosides were isolated from the underground parts of Achlys
      triphylla in addition to eight known compounds. By means of spectroscopic
      analysis, the structures were characterized as isorhamnetin 3-glucosyl(1---
      3)galactoside, isorhamnetin 3-[6''acetylglucosyl(1----3)galactoside],
      isorhamnetin 3-[4''6''-di-acetylglucosyl(1----3)galactoside], and syringetin 3
      [6''-acetylglucosyl(1----3)galactoside], respectively. In the aerial parts of the
      plant, seven known compounds were also confirmed.

PMID- 1367885
TI  - Triterpene saponins from the roots of Ampelozizyphus amazonicus.
AB  - A new triterpene saponin was isolated from the roots of Ampelozizyphus amazonicus
      together with the known 3-O-beta-D-glucopyranosyl-20-O-alpha-L
      rhamnopyranosyljujubogenin and the known triterpenes melaleucic acid, 3 beta,27
      alpha-dihydroxylup-20(29)-en-28 beta-oic acid, betulinic acid, betulin, lupeol.
      The structure of this saponin was elucidated as 3-O-[beta-D-glucopyranosyl(1---
      2)alpha-L-arabinopyranosyl]- 20-O-alpha-L-rhamnopyranosyljujubogenin by spectral
      analysis and chemical transformations.

PMID- 1367886
TI  - Two phenylpropanoid glycosides from Leonurus glaucescens.
AB  - Two new phenylpropanoid glycosides, leonosides A and B, and two known glycosides
      lavandulifolioside and verbascoside, were isolated from the aerial parts of
      Leonurus glaucescens. On the basis of chemical and spectral evidence, leonosides
      A and B were shown to be beta-(3,4-dihydroxyphenyl)-ethyl-O-alpha-L
      arabinopyranosyl-(1---- 2)-alpha-L- rhamnopyranosyl-(1----3)-4-O-feruloyl-beta-D
      glucopyranoside and beta-(3-hydroxy, 4-methoxyphenyl)-ethyl-O-alpha-L
      arabinopyranosyl-(1----2)- alpha-L-rhamnopyranosyl-(1----3)-4-O-feruloyl-beta-D
      glucopyranosi de, respectively.

PMID- 1367887
TI  - Transesterification of phenylalanine by means of chymotrypsin in a continuous
      fixed bed reactor.
AB  - An enzymic transesterification was carried out in a continuously operated fixed
      bed reactor. The reaction system consisted of immobilized alpha-chymotrypsin
      (E.C. 3.4.21.1) catalysing the transfer of the L-phenylalanine radical from the
      racemic propyl ester to 1,4-butanediol, yielding L-phenylalanine 4-hydroxybutyl
      ester. The desired reaction was accompanied by alcoholysis due to the presence of
      1-propanol liberated during the reaction and by hydrolysis of both the propyl and
      the hydroxybutyl ester. The problem of shifting pH during the reaction due to
      ester hydrolysis was overcome by adjusting the initial pH of the substrate feed
      solution appropriately in order to obtain a sufficiently high buffer capacity
      provided by the free amino group of the esters. Thus, it was possible to work
      with shifting pH, an obvious disadvantage for operating reactors of low
      backmixing for this kind of reaction system. The overall reaction scheme was
      characterized by the appearance of a maximum ester yield as a function of the
      operating time in case of batch reactors. Surprisingly, the yield was found to
      become constant as a function of space-time for continuous operation due to a
      steeper pH drop. The maximum productivity achieved with respect to the
      hydroxybutyl ester was about 65 mol d-1 l-1 referred to the catalyst volume.

PMID- 1367889
TI  - Immobilization of pyranose oxidase (Phanerochaete chrysosporium):
      characterization of the enzymic properties.
AB  - Immobilization of pyranose oxidase (E.C.1.1.3.10) from Phanerochaete
      chrysosporium is described. The enzyme was bound to a glass-beaded support
      according to the glutardialdehyde, diazo, and carbodiimide methods with activity
      yields of 10%-23.3%. Characterization of the enzyme immobilized with the
      glutardialdehyde showed enhanced operational, storage, and temperature stability.
      The temperature optimum remained unchanged, but the pH optimum was slightly
      altered. Kinetic properties and the relative substrate specificities for glucose
      and xylose showed certain differences.

PMID- 1367888
TI  - Preliminary assessment of removal of pyrogenic lipopolysaccharides with colloidal
      zirconia adsorbents.
AB  - Preliminary evaluation of bare or polymer-coated colloidal monoclinic zirconia of
      nominal particle size 100 nm indicated that it is an effective adsorbent for
      pyrogenic lipopolysaccharides (LPS) as measured by chemical and Limulus amebocyte
      lysate (LAL) assays. Zirconia at 50 micrograms ml-1 adsorbed 99.95% of added E.
      coli O128 LPS. Residual LPS levels below 0.1 ng ml-1 were easily attained.
      Colloidal zirconia was able to remove LPS from solution in the presence of bovine
      albumin (BSA). Some LPS contaminating BSA lacked affinity for zirconia.
      Preadsorption of phosphate onto bare zirconia blocked LPS adsorption. However,
      phosphated-oligomeric glycidyl (epoxy) pentaerythritol-coated colloidal zirconia
      could be derivatized with imidazole-containing ligands to produce an LPS-binding
      surface. Preliminary results of adsorption of LPS by the coated particles
      indicated a reduced level of LPS binding compared to bare zirconia, probably
      because the particles aggregated during the derivatization process, reducing the
      effective surface available for LPS adsorption.

PMID- 1367890
TI  - Plasmid stabilization of an Escherichia coli culture through cycling.
AB  - The problem of plasmid instability of fermentations that involve plasmid-bearing
      recombinant organisms is dealt with in this work. Previous theoretical work
      demonstrated that under certain conditions (where plasmid-bearing species are
      slower in responding to changes in the fermentation environment than the wild
      species) the washout of the plasmid-bearing species can be prevented. In the
      sequel, Weber and San showed that cycling the dilution rate can delay the washout
      of plasmid-bearing species for a plasmid-bearing Escherichia coli culture. This
      work shows that it is indeed possible to secure the presence of the plasmid
      bearing species at all times through appropriate cycling.

PMID- 1367891
TI  - Cell death in the thin films of bursting bubbles.
AB  - A sparged gas bubble floating at the liquid interface has a liquid film which
      drains and thins until the film spontaneously ruptures at a point. This causes
      rapid retraction of the film, forming a rim of collected fluid. This rim moves at
      a constant velocity of about 3 m/s and any cells in the bubble film are rapidly
      accelerated to this velocity in the moving rim. Half of the surface energy
      originally in the thin film is converted to kinetic energy of the rim, while the
      rest is dissipated in this rim. The rate of energy dissipation per mass of rim
      fluid is approximately 9000 m2/s3, which corresponds to a Kolmogorov eddy size of
      3.2 microns in fully developed turbulence or a shear stress of 95 N/m2 in laminar
      flow. Either of these limiting cases presents an environment in which rapid cell
      death would be expected. Experiments with Sf-9 insect cells suggest that the cell
      concentration in these thin films is 0.6 times the bulk liquid concentration and
      that about 20% of these cells are killed when the film ruptures. An equation
      based on this mechanism accurately predicts the death rate.

PMID- 1367892
TI  - Optimal design of the tubular microporous membrane aerator for shear-sensitive
      cell cultures.
AB  - In this paper, a theoretical analysis of oxygen transport across the tubular
      microporous membrane is described. This analysis has provided some insight into
      the optimal design of the membrane aerator. It was found in this study, at fixed
      inlet pressure, that the overall membrane oxygen transfer rate increases with
      increased tubing length only up to a certain length, i.e., the "critical length".
      When a large membrane surface area is required, the fiber should be divided into
      parallel segments to increase the overall oxygen transfer rate. A manifold or a
      gas distributor can then be used to distribute gas into segments of tubing. The
      length of each segment cannot exceed the critical length. In addition, shorter
      tube segments should give a higher oxygen transfer rate per unit tube length;
      however, this advantage is counterbalanced by the fact that gas distribution into
      huge numbers of parallel tubings may not be uniform.

PMID- 1367893
TI  - Protein release in recombinant Escherichia coli using bacteriocin release
      protein.
AB  - The effect of induction level of the bacteriocin release protein (BRP) on cell
      growth characteristics, protein expression, and protein release in a recombinant
      strain of Escherichia coli RR1 was investigated. Mitomycin C, the inducing agent,
      when added to the growth medium in moderate amounts (up to 200 ng/mL) was
      observed to enhance the release of periplasmic proteins from the cell to the
      fermentation broth substantially. The percentages of release of the proteins
      alpha-amylase and beta-lactamase were increased by factors of about 7 and 3,
      respectively, upon induction of the BRP. The percentage of alpha-amylase released
      into the broth increased from only about 5% to almost 50% with the aid of BRP.
      The cell growth curve and low extracellular activity of the cytoplasmic protein
      beta-galactosidase were indicative that cell lysis did not occur in an
      appreciable amount at a low induction level, with a mitomycin C concentration of
      less than 300 ng/mL.

PMID- 1367894
TI  - Effect of serum on the plasma membrane fluidity of hybridomas: an insight into
      its shear protective mechanism.
AB  - We have previously shown that decreasing the concentration of fetal bovine serum
      (FBS) increased the fragility of a mouse hybridoma (HB-32) during agitated batch
      cultivation and that increasing the plasma membrane fluidity (PMF) increased the
      shear sensitivity during exposure to laminar flow. In this study, the effect of
      FBS concentration on the PMF of HB-32 was investigated. PMF was evaluated by
      steady-state fluorescence anisotropy (rs) of 1-[4-(trimethylamino)phenyl]-6
      phenylhexa-1,3,5-triene. Increasing serum concentration increased the rs of
      hybridomas, indicating a decrease in their PMF. The effect of cholesterol
      modulation on the PMF and shear sensitivity was also evaluated. Hybridomas were
      exposed to turbulent fluid shear after modification of PMF by cholesterol
      modulation. Direct cholesterol enrichment of the plasma membranes caused a
      decrease in the PMF and shear sensitivity, while cholesterol depletion caused an
      increase in PMF and shear sensitivity. Low- and high-density lipoprotein
      supplementation to cultures in serum-free or complete medium decreased their
      shear sensitivity. Lipoprotein supplementation to serum-free cultures decreased
      the PMF. Altogether, these results suggest that the protective mechanism of serum
      against hydrodynamic damage relies, at least partially, on its ability to
      decrease the PMF of hybridomas possibly through the transfer of cholesterol from
      the serum lipoproteins into the plasma membrane.

PMID- 1367895
TI  - Release and recovery of porcine pepsin and bovine chymosin from reverse micelles:
      a new technique based on isopropyl alcohol addition.
AB  - After complete solubilization by the direct method, porcine pepsin was not
      released from AOT in isooctane reverse micelles even under aqueous-phase
      conditions which would not ordinarily allow uptake. Similarly, bovine chymosin,
      once forward-transferred at a pH below its isoelectric point, was not back
      transferred into an aqueous contact phase buffered at a pH value above its
      isoelectric point. These results show that there is significant hysteresis in the
      forward- and backward-transfer processes and further imply that kinetics, and not
      equilibrium, control uptake or release processes for these enzymes. The addition
      of 10-15% isopropyl alcohol to the aqueous phase increases the rate of protein
      release dramatically and allows for nearly complete back-transfer of porcine
      pepsin and 70% back-transfer of bovine chymosin. IPA addition does not destroy
      the functional integrity of the system since forward transfer of bovine chymosin
      still occurs at pH values below (but not above) the pI of the protein.

PMID- 1367896
TI  - In-vitro processing of yeast alpha-factor leader fusion proteins using a soluble
      yscF (Kex2) variant.
AB  - The Saccharomyces cerevisiae KEX2 gene encodes the membrane-bound endoprotease
      yscF, which is responsible for the site-specific endoproteolytic cleavages at
      pairs of basic amino acid residues in the alpha-factor precursor. In order to
      obtain soluble yscF activity, a mutant KEX2 gene lacking 600 bp coding for the C
      terminal 200 amino acids was constructed. Expression of the truncated KEX2 gene
      in yeast led to the secretion of an active soluble yscF protein (yscFs). The
      soluble yscF protein is able to efficiently cleave heterologous protein
      precursors in-vitro, as demonstrated for alpha-factor leader-hIGF1 and alpha
      factor leader-hirudin fusion proteins.

PMID- 1367897
TI  - Fermentation study for the production of hepatitis B virus pre-S2 antigen by the
      methylotrophic yeast Hansenula polymorpha.
AB  - Various physico-chemical parameters have been studied in order to improve the
      production of hepatitis B virus pre-S2 antigen (middle surface antigen) by the
      methylotrophic yeast Hansenula polymorpha. Antigen production was done in two
      steps: first, production of cells on glycerol (Phase 1), followed by induction of
      antigen expression with methanol (Phase 2). Dense cultures of H. polymorpha,
      equivalent to 35-40 g/l (dry weight), were readily obtained in small fermenters
      using minimal medium containing glycerol as carbon source. Antigen expression in
      this minimal medium, after induction with methanol, was however, low and never
      exceeded 1.6 mg/l of culture. Antigen production was greatly enhanced by adding
      complex organic nitrogen sources along with methanol at induction time; yeast
      extract was the best of all the sources tested. In shake flasks, antigen
      production was proportional to yeast extract concentration up to 7% (w/v) yeast
      extract, it became clear the the nutritional conditions for good antigen
      expression were different from those for good biomass production. The effects of
      yeast extract were reproduced in small fermenters: antigen levels reached 8-9
      mg/l in medium containing 6% (w/v) yeast extract during induction with methanol.
      The mechanisms of yeast extract's effects are still unknown but are probably
      nutritional. The recombinant H. polymorpha strain produced both periplasmic and
      intracellular antigen. The periplasmic antigen was shown to be present as 20-22
      nm particles and was therefore immunogenic. Immunoblotting indicated that part of
      the pre-S2 antigen was present as a 24-kDa degradation product. These studies
      have led to a 140-fold increase in volumetric productivity of antigen and to a
      4.6-fold increase in specific production.

PMID- 1367898
TI  - Bioconversion of the sodium salt of simvastatin (MK-733) to 6-desmethyl-6-alpha
      hydroxymethyl simvastatin.
AB  - An actinomycete (MA 6474, ATCC 53828) isolated from a soil sample (Mutare,
      Zimbabwe) was found to biotransform the sodium salt of Simvastatin (MK-733) to 6
      alpha-hydroxymethyl MK-733, 6-beta-hydroxymethyl MK-733, and 6-ring-hydroxy MK
      733. The bioconversion efficiency to the desired compound, 6-alpha-hydroxymethyl
      MK-733, was enhanced by optimizing the physico-chemical parameters of the
      process. In shake flask cultures, addition of magnesium (0.125 mg/l Mg SO4.7H2O)
      to the medium resulted in a five-fold increase in the rate of bioconversion to
      the alpha diastereomer. The ratio of bioconversion products (6-alpha
      hydroxymethyl,6-beta-hydroxymethyl, and 6-ring-hydroxy MK-733) was regulated by
      pH. Process improvements and scale up in 23-1 fermentors, which consisted of a
      controlled addition of substrate (MK-733), resulted in a 2-fold increase in alpha
      diastereomer production (42 vs. 79 U/ml) and a 23-fold rate increase in the
      formation of alpha-diastereomer. A high diastereomeric ratio (alpha: beta = 9:1)
      facilitated downstream processing.

PMID- 1367899
TI  - Metabolic roles of peptone and yeast extract for the culture of a recombinant
      strain of Escherichia coli.
AB  - The influence of complex compounds on the growth of a recombinant strain of
      Escherichia coli containing the gene encoding glyceraldehyde 3-phosphate
      dehydrogenase, as well as the production of this enzyme have been studied.
      Batchwise cultures led to an accumulation of acetate, which was not utilized in a
      yeast extract-free medium. After glucose exhaustion, growth stopped and enzyme
      activity decreased. Whereas yeast extract allowed acetate assimilation and
      growth, peptone stabilized the enzymatic activity. The addition of both compounds
      resulted in optimal performances for enzyme production.

PMID- 1367900
TI  - Effect of cultural conditions on production of eicosapentaenoic acid by Pythium
      irregulare.
AB  - The effect of culture conditions upon lipid content and fatty acid composition of
      mycelia of Pythium irregulare was investigated with particular attention to
      increasing the yield of 5,8,11,14,17-eicosapentaenoic acid (20:5; omega-3)(EPA).
      All experiments were done by shake flask culture using a yeast extract + malt
      extract medium. The maximum growth rate was obtained at 25 degrees C, but maximum
      EPA production was obtained at 12 degrees C. The highest EPA production was 76.5
      micrograms EPA/ml 13 days fermentation at 12 degrees C. Addition of glucose
      during fermentation increased the yield considerably. The highest yield was 112
      micrograms/ml, obtained at 13 days fermentation with spiking on day 11.
      Fermentation time could be shortened by initial incubation at 25 degrees C for 2
      days, followed by incubation at 12 degrees C for 6 days. The culture also
      produced arachidonic acid and other omega-6 polyunsaturated fatty acids. EPA
      production was also obtained with lactose or sweet whey permeate, a by-product of
      cheese manufacture that contains lactose as the main carbohydrate.

PMID- 1367901
TI  - Production of arachidonic acid by Mortierella alpina ATCC 32222.
AB  - When Mortierella alpina ATCC 32222 was incubated in a glucose salts medium at 25
      degrees C the biomass (17.5 g/l) contained 9.62% arachidonic acid which amounted
      to 54% (w/w) of total biomass lipids. When the glucose concentration in the
      medium was varied from 0 to 150 g/l, the percentage of arachidonic acid in
      biomass and in lipids was highest at a glucose concentration of 30 g/l, but
      highest yield of arachidonic acid per litre of culture broth was observed at a
      glucose concentration of 100 g/l. While production of biomass reached a plateau
      of 17 g/l after a 3-day incubation at 25 degrees C, the percentage of arachidonic
      acid in lipids and biomass increased dramatically from 3 to 6 days with a
      concurrent arachidonic acid yield increase from 0.89 to 1.63 g/l. Optimum initial
      culture pH for arachidonic acid production was in the range 6.0-6.7. By
      increasing the concentration of the glucose salts medium three-fold, yields of
      biomass and arachidonic acid were increased to 35.8 g/l and 3.73 g/l,
      respectively.

PMID- 1367902
TI  - Genus- and species-specific oligonucleotide probes derived from 16S rRNA for the
      identification of vagococci.
AB  - Synthetic oligonucleotide probes specific for vagococci were designed from 16S
      rRNA sequence data. Molecular hybridizations with PCR-amplified rDNA targets
      provided an unequivocal means of differentiating vagococci from related lactic
      acid bacteria (eg. Carnobacterium, Enterococcus, Lactococcus) and identification
      at the generic and species levels.

PMID- 1367903
TI  - Increase of xanthan production by cloning xps genes into wild-type Xanthomonas
      campestris.
AB  - Previously, genomic banks of Xanthomonas campestris were constructed in
      Escherichia coli, using mobilizable broad-host-range cosmids as the vectors.
      Following conjugal transfer, genes involved in the biosynthesis of xanthan
      polysaccharide (XPS) were cloned by the ability to restore the mucoid phenotype
      to the non-mucoid mutants. In this study, all clones were transferred into the
      wild-type strain Xc17 to evaluate the effects of the cloned genes on XPS
      production. Most clones showed no significant effect; however, two plasmids,
      pP2401 and pP2201, caused 10 and 15% yield increases, respectively, compared with
      that of controls. While it was not clear how pP2201 caused the yield increase,
      the effect of pP2401 seemed to result from elevated phosphomannose isomerase
      activity. Since XPS synthesis in X. campestris is a very efficient process, only
      relatively small increases are to be expected; an enhancement of productivity by
      10-15% is important to the commercial production of xanthan.

PMID- 1367904
TI  - Comparison of a competitive enzyme immunoassay kit and the infant mouse assay for
      detecting Escherichia coli heat-stable enterotoxin.
AB  - A commercial competitive enzyme immunoassay kit, Escherichia coli ST EIA, was
      compared with the conventional infant mouse assay for sensitivity and specificity
      in detecting E. coli heat-stable enterotoxin. Thirty-one of 46 strains of E. coli
      tested were positive by both assays, while 15 strains were negative. The
      sensitivity of the ST EIA kit was up to 64-fold lower than the infant mouse
      assay.

PMID- 1367905
TI  - Electrotransformation of Xanthomonas campestris by RF DNA of filamentous phage
      phi Lf.
AB  - Conditions were optimized for electrotransformation of Xanthomonas campestris pv.
      campestris by the replicative form (RF) DNA of filamentous phase phi Lf. Early
      logarithmic cells were washed exhaustively with deionized water and subjected to
      a pulse at a field strength of 12.5 kV/cm with a 25 microF capacitor and a 400
      omega resistor. An efficiency of 5.1 x 10(7) pfu per microgram RF DNA was
      obtained. Under the same conditions, the broad host range plasmid pLAFR1 (21.6
      kb) transformed X. campestris strains at efficiencies around 10(5) pfu per
      microgram DNA prepared from XcP20H. The advantages of the protocol used in the
      present study are that the cells can be washed with water instead of complex
      buffer, and the DNA used can be prepared by the alkaline method of Birnboim &
      Doly without purification by ultracentrifugation.

PMID- 1367906
TI  - Adaptation of hybridoma cells to higher ammonia concentration.
AB  - Using two mouse-mouse hybridoma cell lines, the response to ammonia step and
      serial changes was investigated in batch and continuous cultures with serum-free
      medium. The inhibitory effect of ammonia on cell growth depended on the
      cultivation mode, and differed markedly between cell lines. The cell line, 4C10B6
      producing IgG monoclonal antibody against Pseudomonas, showed a high adaptation
      ability to ammonia. The 4C10B6 cells could grow under ammonia concentration as
      high as 21 mmol/l NH4Cl with a viability of 80% in the continuous culture with
      serial increase in ammonia concentration. Whereas, in the batch culture with
      ammonia step change the cell growth completely ceased at 12 mmol/l NH4Cl. The
      other cell line, TO-405 producing IgG monoclonal antibody against hepatitis B
      surface antigen, could not adapt to ammonia, and the cell growth did not occur at
      9 mmol/l NH4Cl even under the ammonia serial change.

PMID- 1367907
TI  - A new method for the encapsulation of mammalian cells.
AB  - A new encapsulation method was developed for the cultivation of mammalian cells.
      The capsules were produced using a solution of sodium cellulose sulphate
      (CS)(1.5%) and poly-dimethyl-diallyl-ammonium chloride (PDMDAAC). When CS
      droplets fell into the precipitation bath consisting of a 2% solution of PDMDAAC,
      immediately a membrane at the interphase was built up. The influences of varying
      encapsulation process parameters on capsule characteristics, cell growth, and
      monoclonal antibody production were tested. This new method showed advantages
      when compared to other methods mainly due to time simplicity of the whole
      process.

PMID- 1367908
TI  - The medium cycle bioreactor (MCB): monoclonal antibody production in a new
      economic production system.
AB  - The perfusion mode of a continuous cell culture bioreactor was modified to
      establish a closed loop system. Eighty percent of the spent medium was re-used
      twice. The medium cycle bioreactor unit was operated sterile and uncomplicated
      without a technical retention system for the high molecular weight substances.
      Therefore, only 20% of the actual medium was necessary to run the recycling
      process. During seven days culture time in a two liter scale 5 grams of IgG1 type
      monoclonal antibody was produced. During that period the cell specific
      productivity was constant. Renewal of proteins was omitted because the protein
      content in the system persisted at a high level. Therefore, self-conditioning
      substances of the cells were retained in the system as well as the expensive
      medium components (proteins with catalytic or stimulating function). Seventy to
      80% of medium costs and medium quantity were saved for each medium recycling
      step. Only cheap metabolites that are consumed by the cells had to be
      supplemented. Uptake rates of glucose and amino acids were calculated to
      establish a suitable supplementation mixture for the recirculated medium.

PMID- 1367909
TI  - Development of a new culture system for human lymphokine-activated killer cells:
      comparison with a conventional static culture method.
AB  - We recently developed a new culture system based on dialysis perfusion
      (designated JCC-device) for the generation and expansion of human lymphokine
      activated killer (LAK) cells (Murata et al., 1990). More recently we have scaled
      up the volume of the culture vessel of the JCC-device from 100 ml to 400 ml for
      clinical use. In the present study, using this new 400 ml JCC-device, we cultured
      human lymph node lymphocytes (LNL) obtained from 8 surgical patients with primary
      lung cancer, and investigated the cellular characteristics in comparison with a
      conventional batchwise culture system using tissue culture dishes. With the JCC
      device, the cell density reached a maximum 2.7 x 10(7) cells/ml with greater than
      90% viability by the appropriate exchange of perfusion medium and by making
      additions at the appropriate intervals for recombinant interleukin-2 (rIL-2). The
      expansion fold of LNL with the JCC-device, ranging 6.6- to 19.2-fold (mean 13.8
      fold), was not significantly different from that in dish cultures. There was no
      marked difference in cell surface phenotypes between the two culture systems in 7
      out of 8 cases. As for LAK activity of LNL, the JCC culture was either superior
      or equal in 4 out of 8 cases, but inferior in the other 4 cases to the
      conventional dish cultures. In the latter cases, the usage of serum for the JCC
      culture was limited, which might have resulted in the low LAK activity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1367912
TI  - Gene expression using streptomycetes.

PMID- 1367911
TI  - Enhancing effect of mouse peritoneal exudate cells and their products on antibody
      productivity of hybridoma cells: application of in vivo factors to in vitro
      culture.
AB  - Mouse peritoneal exudate cells induced by casein enhanced in vitro antibody
      production rate per cell of a hybridoma in co-culture. Culture supernatant of the
      exudate cells also enhanced three-fold the antibody productivity when added to
      cultures of a hybridoma at 10% (v/v). Hence the enhancement of antibody
      productivity by the exudate cells seemed to be caused by soluble enhancing
      factors secreted by the exudate cells. The exudate cells maximally secreted the
      enhancing factors when harvested from mice on day 4 of the induction period
      following the injection of casein. A semi-continuous culture of the hybridoma
      demonstrated the applicability of the culture supernatant to enhance antibody
      production by producing a two-fold increase over the control for seven days when
      supplemented with the supernatant at 5%. Significant amounts of interleukin-6
      were detected in culture supernatant of the exudate cells. Interleukin-6 obtained
      from other sources enhanced the antibody productivity two-fold when added to the
      hybridoma culture at the concentration of 5 unit/ml. Interleukin-6, therefore, is
      expected to be one of the principal antibody enhancing factors secreted by the
      exudate cells. Other interleukins examined, that is, interleukin-1 to -5 did not
      enhance the antibody productivity.

PMID- 1367910
TI  - Effects of cell density and phorbol esters on the expression of epidermal growth
      factor receptors.
AB  - Previously, it has been shown that the binding of epidermal growth factor (EGF)
      by a wide range of cells decreases as cell density increases. In this report, we
      demonstrate that KB cells treated chronically with phorbol esters continue to
      exhibit decreases in EGF receptor binding as cell density increases. This finding
      suggests that protein kinase-C may not be essential for density-induced down
      regulation of EGF receptors, since phorbol esters are known to down regulate
      protein kinase-C. We also report that short-term and long-term effects of phorbol
      esters on the binding of EGF are affected by density. As shown previously for
      several cell lines, the phorbol ester 12-0-tetradecanoylphorbol-13-acetate
      transiently reduces EGF binding. We now show that the magnitude of this reduction
      diminishes as cell density increases. In addition, we determined that long-term
      treatment of KB cells with phorbol ester increases EGF binding. Again, this
      effect is diminished at high cell densities. Finally, we report that the
      increases in EGF binding induced by long-term treatment with phorbol esters are
      due to increases in the number of EGF receptors.

PMID- 1367913
TI  - Gene expression using Bacillus.

PMID- 1367914
TI  - Gene expression and engineering in yeast and other fungi.

PMID- 1367915
TI  - Expression systems.

PMID- 1367916
TI  - Mammalian cell expression.

PMID- 1367918
TI  - Gene expression using insect cells and viruses.

PMID- 1367917
TI  - Gene expression using retroviral vectors.

PMID- 1367919
TI  - Transgenic animals--production of foreign proteins in milk.

PMID- 1367920
TI  - Gene expression using cell-free systems.

PMID- 1367921
TI  - Expression in Xenopus oocytes.

PMID- 1367923
TI  - Expression systems.

PMID- 1367922
TI  - Manipulating gene expression by ribozyme technology.

PMID- 1367924
TI  - The genome race is on the road.

PMID- 1367925
TI  - Sequencing the yeast genome: the European effort.
AB  - For ethical, practical and economic reasons, scientists have traditionally relied
      on model organisms for biological research. Although model organisms do not
      always quite constitute the 'real thing', the significant advantages of their use
      contribute to making their study a viable alternative. The decision to use a
      specific model, particularly in large-scale studies such as genome projects, will
      be governed not only by biological consideration, but also by the prevailing
      financial and organizational infrastructure and expertise of the research
      community.

PMID- 1367926
TI  - Model genomes: the benefits of analysing homologous human and mouse sequences.
AB  - The human genome initiative has provided the motivating force for launching
      sequencing projects suitable for testing various DNA-sequencing strategies, as
      well as motivating the development of mapping and sequencing technologies. In
      addition to projects targeting selected regions of the human genome, other
      projects are based on model organisms such as yeast, nematode and mouse. The
      sequencing of homologous regions of human and mouse genomes is a new approach to
      genome analysis, and is providing insights into gene evolution, function and
      regulation which could not be determined so easily from the analysis of just one
      species.

PMID- 1367927
TI  - Using chromosome features in genome mapping.
AB  - Studies of the structure and function of chromosomal features and sequence
      elements have much to contribute to and gain from genome mapping. Abnormalities
      in chromosome banding associated with specific diseases have pinpointed regions
      of the genome for intensive analysis. An improved understanding of chromosome
      organization can facilitate gene identification and isolation, as well as
      enabling sophisticated genetic and vector systems for genome studies to be
      devised.

PMID- 1367928
TI  - Using fluorescence in situ hybridization (FISH) in genome mapping.
AB  - Fluorescence in situ hybridization (FISH) provides one of the most effective and
      rapid approaches for assigning and ordering DNA fragments within single
      eukaryotic chromosome bands. These techniques have wide applications not only for
      the mapping of the human genome and the genomes of other organisms, but also in
      clinical cytogenetics, somatic cell genetics, cancer diagnosis and gene
      expression studies.

PMID- 1367929
TI  - Generating 'cloned DNA maps'.

PMID- 1367930
TI  - Yeast artificial chromosomes (YACs) and the analysis of complex genomes.
AB  - The development of yeast artificial chromosome (YAC) cloning vectors capable of
      carrying several hundred kilobase-pairs of DNA insert has greatly facilitated the
      study of complex genomes, and the cloning of large genes as single fragments. In
      addition, the ability to manipulate YAC sequences by homologous recombination
      makes this system extremely useful for the generation of disease models.

PMID- 1367932
TI  - PCR amplification techniques for chromosome walking.

PMID- 1367931
TI  - Coincident sequence cloning: a new approach to genome analysis.
AB  - Many analytical molecular genetic techniques developed over the past decade have
      evolved primarily to tackle the problem of targeting or isolating sequences of
      interest in complex mixtures. A new approach to this problem, Coincident Sequence
      Cloning (CSC), involves integrating a pair of DNA mixtures in such a way as to
      isolate any shared sequence components.

PMID- 1367933
TI  - Chromosome microtechnology: microdissection and microcloning.
AB  - The physical microdissection of chromosomes and subsequent microcloning of
      dissected fragments is enabling the generation of very large numbers of cloned
      unique sequences from defined chromosomal regions. In addition to use in
      constructing region-specific libraries of the entire human genome and providing
      probes for mapping and sequencing purposes, such chromosome microtechnology
      should facilitate the search for disease-associated genes in defined chromosome
      regions.

PMID- 1367934
TI  - Semi-automated solid-phase DNA sequencing.
AB  - Increasing the efficiency of DNA sequencing necessitates the development of
      systems which reduce the need for manual operations by integrating template
      preparation, sequencing reactions, product separation and detection. A semi
      automated system, whereby PCR-amplified biotinylated genomic or plasmid DNA is
      immobilized on streptavidin-coated magnetic beads, has been developed.

PMID- 1367935
TI  - Single-molecule detection as an approach to rapid DNA sequencing.
AB  - Current sequencing technologies are insufficient to cope with large-scale
      projects such as sequencing the human genome and genomes of model organisms. In
      addition, as genetic lesions associated with specific human diseases are
      identified, DNA sequencing will be used increasingly for clinical applications.
      Thus, new approaches are needed to combine high-throughput with accuracy for both
      research and diagnostic purposes. A novel technology based on detection of
      individual fluorescent nucleotides in a flowing sample stream is under
      development.

PMID- 1367937
TI  - Budgeting the genome.

PMID- 1367936
TI  - Data exchange and inter-database communication in genome projects.

PMID- 1367938
TI  - Molecular biological databases--present and future.
AB  - The importance of databases as a research tool in molecular biology is growing
      steadily, and a wide range of databases relevant to genome research is currently
      available. However, the design of current databases is inadequate for accurate
      representation and analysis of the results of large-scale genome mapping and
      sequencing projects. A new generation of databases is required to master the
      challenges of the future.

PMID- 1367939
TI  - An artificial intelligence approach to DNA sequence feature recognition.
AB  - The ultimate goal of the Human Genome project is to extract the biologically
      relevant information recorded in the estimated 100,000 genes encoded by the 3 x
      10(9) bases of the human genome. This necessitates development of reliable
      computer-based methods capable of analysing and correctly identifying genes in
      the vast amounts of DNA-sequence data generated. Such tools may save time and
      labour by simplifying, for example, screening of cDNA libraries. They may also
      facilitate the localization of human disease genes by identifying candidate genes
      in promising regions of anonymous DNA sequence.

PMID- 1367940
TI  - Nonprofit biological resource centers.

PMID- 1367941
TI  - Genome sequence analysis: scientific objectives and practical strategies.

PMID- 1367942
TI  - Improved selection systems for man-made antibodies.

PMID- 1367943
TI  - The human genome: beyond the bases.

PMID- 1367944
TI  - Phage antibodies: will new 'coliclonal' antibodies replace monoclonal antibodies?
AB  - Antibodies can now be rapidly isolated from large and diverse recombinant
      libraries by displaying functional antibody fragments on the surface of
      bacteriophage particles and directly selecting with antigen. This method has been
      used to isolate antibodies, including human antibodies, with and without
      immunization, and to improve the affinity and specificity of antigen binding.

PMID- 1367946
TI  - Probing identity: the changing face of DNA fingerprinting.
AB  - DNA-fingerprinting technology has made a very rapid transition from being a
      research laboratory discovery to an applied science widely understood by, and of
      interest to, the general public. However, DNA fingerprinting is often portrayed
      as being a single generic technology, rather than a complex evolving mixture of
      methodologies, where specific applications demand selection of appropriate probes
      and techniques.

PMID- 1367945
TI  - Recombinant haemoglobin in the development of red-blood-cell substitutes.
AB  - Increasing concern over viral contamination of blood is spurring the development
      of a blood substitute which can effectively replace the oxygen-carrying
      capabilities of transfused erythrocytes. Solutions of chemically modified
      haemoglobin represent one option being evaluated for this role. More recently,
      recombinant-DNA techniques have enabled production of human haemoglobin in host
      expression systems, and progress is being made towards the creation of a
      genetically engineered molecule incorporating the properties required of a blood
      substitute.

PMID- 1367947
TI  - Biotechnological applications of image analysis: present and future prospects.
AB  - The current and potential biotechnological applications of image analysis and
      image processing systems are reviewed. Image analysis systems have proven to be
      highly versatile and efficient tools for assisting academic biotechnological
      research. It is expected that image analysis systems will allow more rapid and
      accurate quantification of numerous biotechnological analyses. There is,
      therefore, much scope for the implementation of image analysis/processing systems
      in a large variety of industrial and clinical applications.

PMID- 1367948
TI  - Processing of the prepropeptide portions of the Bacillus amyloliquefaciens
      neutral protease fused to Bacillus subtilis alpha-amylase and human growth
      hormone during secretion in Bacillus subtilis.
AB  - A set of nested 3'-terminal deletions of the prepropeptide of the Bacillus
      amyloliquefaciens neutral protease gene was constructed. Alpha-amylase and human
      growth hormone were secreted using these truncated genes in Bacillus subtilis.
      The level of the secreted alpha-amylase varied with the region for the truncated
      prepropeptide contained in the fusion gene but was independent of its length.
      Even though length of the prepropeptide varied, the mobilities of secreted alpha
      amylases were the same as that of the control alpha-amylase derived from the
      alpha-amylase clone, pTUB4 (Yamazaki et al., 1983). Analyses of the secreted N
      terminal amino acid sequences confirmed that they were all identical to that of
      the authentic one. Precursor proteins of the alpha-amylase were found in the cell
      associated fraction, suggesting that the prepropeptide portion was processed
      during secretion. On the other hand, the N-terminus of hGH secreted using one of
      these prepropeptide portions varied by 1 to 4 additional N-terminal amino acid
      residues derived from the junction sequence between the sequence for propeptide
      portion and mature hGH or from C-terminal region of the propeptide portion. These
      results suggest that the prepropeptide portion can be generally processed even in
      the heterogeneous fusion. A probable mechanism of processing and maturation of
      the fusion gene products is also discussed.

PMID- 1367949
TI  - A geometric interpretation of the feasibility of reactive extraction/re
      extraction of penicillin G.
AB  - The reactive extraction (re-extraction) of penicillin G from reaction mixtures is
      based on complexation with a carrier and subsequent dissociation of the complex.
      An established mathematical model for this has been analysed to develop a
      feasibility domain within which the process may be designed and optimised.
      Geometric and physical interpretations of this domain are provided.

PMID- 1367950
TI  - Globin gene switching: a paradigm or what?
AB  - The delineation of the beta-globin locus control region has led to a new
      understanding of the developmental regulation of the beta-globin gene cluster. It
      now seems that globin gene switching is effected through the sequential and
      mutually exclusive interaction of the locus control region with the embryonic,
      fetal and adult stage specific globin genes.

PMID- 1367951
TI  - Structural and functional diversity of the platelet-derived growth factor.
AB  - The platelet derived growth factor is the most potent mitogen for cells of
      mesenchymal origin. Recent investigations have identified and characterized the
      structures and genes of the isoforms of PDGF, of the isoforms of its receptor,
      and of genes activated by it. It is now possible to understand in part the
      striking diversity of activities mediated by platelet derived growth factor and
      to identify new roles for it in normal and abnormal cell growth, in inflammation
      and repair, and in mammalian development.

PMID- 1367952
TI  - Studies in oncogenes.
AB  - Advances are being made at an increasing rate towards an understanding of the
      role of cellular oncogenes in the normal and transformed cell. This review
      highlights a number of studies looking at the role of these genes in the
      carcinogenic process using in vivo and in vitro systems.

PMID- 1367953
TI  - Genetic basis of cancer.
AB  - Tumorigenesis is a heterogeneous process that occurs over a relatively long time
      span, progressing from a single cell through intermediate stages to give rise to
      a tumour that becomes more aggressive over time. Recent discoveries have begun to
      define the molecular events that underlie this progression in breast and colon
      cancer.

PMID- 1367954
TI  - Genetic marker technology.
AB  - Advances in our understanding of polymorphisms found in eukaryotic genomes and
      improved methods for studying genetic markers should facilitate genetic linkage
      mapping and other applications. Progress within the past year includes
      characterization of the types, frequencies, and properties of tandemly repeated
      sequences, methods for obtaining the DNA sequence flanking genetic markers for
      use in the polymerase chain reaction, and new detection systems featuring
      automation and multiplexing.

PMID- 1367955
TI  - Modifying the mammalian genome by gene targeting.
AB  - Over the past year, gene targeting in mammalian cells has become a facile
      technology. By using a variety of selection and screening protocols, it has
      become possible to direct modifications at the nucleotide level to specific
      genes, to target marker genes so that they become expressed under the control of
      endogenous promoters and to delete large regions of the genome.

PMID- 1367956
TI  - Mouse models of human diseases.
AB  - Cancer, poliomyelitis, Alzheimer's and Gaucher disease, a seemingly disparate
      array of disorders, have become the target of powerful genetic analysis and drug
      screening protocols, using mouse strains that have been genetically altered to
      serve as models for understanding the disease and for helping the patient.

PMID- 1367957
TI  - The application of transgenic techniques for the improvement of domestic animal
      productivity.
AB  - The application of transgenesis techniques to domestic animals has now been
      achieved in all the major species of domestic animals. In this review, the
      progress towards genuine practical applications of the technique is examined.
      Areas which appear to have made progress during the past several years include
      the evaluation of animals with elevated growth hormone levels, the introduction
      of novel metabolic pathways, the expression of transgenes in the mammary glands
      of pigs and sheep, and the real possibility that functional immunoglobulin genes
      might be used to confer genetically-inherited disease resistance to commercially
      valuable animal breeds.

PMID- 1367958
TI  - Gene therapy techniques.
AB  - The most dramatic event of the past year in the field of gene therapy has been
      the initiation of clinical trials involving the introduction of genetically
      altered cells into human beings. Four studies, three involving new approaches to
      cancer therapy and one involving the treatment of adenosine deaminase deficiency,
      are presently under way. There has also been significant recent progress in the
      technology of gene transfer relevant to gene therapy. This progress, along with
      the recent clinical therapy trials, is the subject of this review.

PMID- 1367959
TI  - alpha-Interferon in hematological malignancies.
AB  - Recent studies have generated data demonstrating significant clinical activity of
      alpha-interferon therapy in each of six hematological malignancies, chronic
      myeloid leukaemia, essential thrombocythemia, polycythemia rubra vera, non
      Hodgkin's lymphomas, multiple myelomatosis and hairy cell leukaemia.

PMID- 1367960
TI  - Growth factors as wound healing agents.
AB  - Wound healing can no longer be considered a generic term: it is the summation of
      a complex series of processes beginning with coagulation and ending in
      remodelling. This review, therefore, summarizes the past year's advances in
      growth factor research according to the roles of the individual growth factors in
      the specific processes of the wound healing scheme.

PMID- 1367961
TI  - Novel agents that promote bone regeneration.
AB  - Regulation of bone growth is controlled partly by local growth factors, which
      have effects on bone including the differentiation of precursor cells, osteoblast
      proliferation, the stimulation of matrix synthesis and angiogenesis. These
      factors are hypothesized to have a role in augmenting bone repair. In the past
      year, recombinant technology has provided sufficient material to allow extensive
      in vivo evaluation of this hypothesis.

PMID- 1367962
TI  - Inhibition of cytokine function: potential in autoimmune disease.
AB  - Multiple lines of evidence implicate cytokines in the pathogenesis of autoimmune
      and inflammatory diseases. Neutralization of the biological activities of
      cytokines by interfering with ligand binding to specific cell-surface cytokine
      receptors thus represents an approach to controlling such diseases. Several
      agents, including novel, receptor-based antagonists, are being developed and
      tested in disease models.

PMID- 1367963
TI  - Major histocompatibility complex binding peptides: a target for therapeutic
      development.
AB  - Peptides that bind with high affinity to major histocompatibility complex
      molecules could represent useful tools in treating class II-associated autoimmune
      diseases such as rheumatoid arthritis, type 1 diabetes and multiple sclerosis.
      Although the concept has been validated in experiments with both purified
      receptor systems in vitro and cellular systems in vivo, many challenging problems
      need to be resolved before efficacious therapeutic agents are obtained.

PMID- 1367964
TI  - Recombinant subunit vaccines.
AB  - Research that may lead to the development of recombinant DNA-based vaccines has
      been conducted on a broad front. This has resulted in an increased understanding
      of immunological responsiveness to vaccines, the rational engineering of
      immunogens, and new means of delivering vaccines.

PMID- 1367965
TI  - Perspectives on the development of anti-HIV vaccines.
AB  - Progress towards the development of a vaccine against acquired immune deficiency
      syndrome is proceeding along several fronts. First and foremost, it rests on the
      basic research being done with the virus, particularly its mechanisms of
      replication, pathogenesis and evolution. More directly, progress comes from
      studies of animal models with the simian and human immunodeficiency viruses where
      vaccine candidates have proven effective in blocking infection. Principally
      because the animal models cannot answer all of the critical questions that apply
      to a vaccine for man, parallel studies in human volunteers have been initiated.

PMID- 1367967
TI  - Mammalian gene studies.

PMID- 1367966
TI  - Antisense oligonucleotides for therapeutic intervention.
AB  - Advances have been made in defining the best target sequences for use in
      antisense oligonucleotide technology, and new chemical derivatives of
      oligonucleotides are being investigated. Although the potential use of antisense
      oligonucleotide agents in the treatment of neoplastic, viral and parasitic
      diseases continues to be explored, they are not yet suitable for administration
      to humans for reasons that are discussed.

PMID- 1367968
TI  - Pharmaceutical applications.

PMID- 1367969
TI  - The N-terminal amino acid sequence of the beta-subunit of the legumin-like
      protein from seeds of Ginkgo biloba.
AB  - The sequence of the first 52 amino acids at the N-terminus of the beta-subunit of
      a legumin-like protein from seeds of the gymnosperm Ginkgo biloba were determined
      by automated sequencing and DABITC/PITC microsequence analyses of peptides
      derived from the protein by enzymatic digestions and chemical cleavage with CNBr.
      The protein from Ginkgo exhibits sequence homologies (32-49% identities) with the
      11S globulins and legume-like proteins from seeds of various angiosperm
      monocotyledons and dicotyledons.

PMID- 1367970
TI  - Heterogeneity of carrageenans from Chondrus crispus.
AB  - Carrageenans extracted from gametophytic and sporophytic Chondrus crispus were
      analysed by hydrolysis, KCl fractionation and 1H NMR spectroscopy. The
      carrageenan from gametophytic plants is composed predominantly of two KCl
      insoluble fractions which contain kappa-carrageenan as the major component with 1
      carrageenan and sulphated galactans as minor components. The precursor mu- and v
      carrageenans were not found in the soluble fraction. The extract from sporophytic
      plants is composed mainly of a KCl soluble fraction which could be separated into
      10 fractions by ion-exchange chromatography. The major component did not show a
      lambda-type structure but one of a xi-carrageenan.

PMID- 1367971
TI  - Virgaureasaponin 3, a 3,28-bisdesmosidic triterpenoid saponin from Solidago
      virgaurea.
AB  - A new 3,28-bisdesmosidic triterpenoid glycoside was isolated from the mixture of
      deacylated saponins from the aerial parts of Solidago virgaurea. The structure of
      virgaureasaponin 3 was determined as 3-O-beta-D-glucopyranosyl-(1----3)-beta-D
      glucopyranosylpolygalacic++ + acid 28-O-beta-D-fucopyranosyl-(1----2)-alpha-L
      rhamnopyranosyl-(1----3)-beta -D- xylopyranosyl-(1----4)-alpha-L-rhamnopyranosyl
      (1----2)-beta-D-fucopyran oside mainly by various 2D NMR techniques.

PMID- 1367972
TI  - A spirostanol glycoside from Yucca aloifolia.
AB  - From an ethanolic extract of the influorescence of Yucca aloifolia a new
      spirostanol glycoside has been isolated and characterized as 3-O[(alpha-L
      rhamnopyranosyl(1----3)-beta-D-xylopyranosyl(1----2))(beta- D-glucopyranosyl(1---
      3)-beta-D-glucopyranosyl(1----3)-beta-D-glucopy  ranosyl]-25R,5 alpha-spirostan-2
      alpha, 3 beta-diol.

PMID- 1367973
TI  - Effect of the levels of dissolved oxygen on the expression of recombinant
      proteins in four recombinant Escherichia coli strains.
AB  - Four recombinant strains of Escherichia coli were examined for the effects of the
      dissolved oxygen level on the level of biomass, the plasmid content, and the
      level of recombinant protein at the stationary phase of batch growth. Strains
      JM101/pYEJ001, and TB-1/pYEJ001 (encoding chloramphenicol acetyltransferase), and
      strain TB-1/p1034, and TB-1/pUC19 (encoding beta-galactosidase) were grown at the
      constant dissolved oxygen levels of 0, 50, and 100% air saturation, as well as in
      the absence of dissolved oxygen control. The biomass of all strains under
      constant aerobic conditions was 12-36 times higher than that under anaerobic
      conditions, but was the same as or slightly higher than that without dissolved
      oxygen control. The plasmid content in all strains under aerobic conditions was
      2.9-11.7 times higher than that under aerobic conditions. The optimal dissolved
      oxygen concentration for the specific activity of recombinant proteins was
      dependent upon the strain. In no strain were constant aerobic conditions optimal.
      However, because of the effect on biomass, controlled aerobic conditions were
      optimal for the volumetric activity of recombinant protein in all but one strain.

PMID- 1367974
TI  - Fate in water of a recombinant Escherichia coli K-12 strain used in the
      commercial production of bovine somatotropin.
AB  - The fate in water of Escherichia coli K-12 strain LBB269, both plasmid-free and
      carrying the recombinant plasmid pBGH1, was studied. E. coli K-12 strain LBB269
      (pBGH1) is a nalidixic acid resistant derivative of W3110G (pBGH1), the
      microorganism used by Monsanto Company for the commercial production of bovine
      somatotropin. Water samples were obtained from the Missouri River and from the
      Monsanto Life Sciences Research Center aqueous waste basin. Strains LBB269 and
      LBB269 (pBGH1) were grown in fermentation vessel under bovine somatotropin (BST)
      production conditions, and inoculated into the water samples. The inoculated
      water samples were incubated at 26 degrees C, and the number of viable E. coli
      cells was determined as a function of time. In sterile water from both sources,
      the two strains remained at a constant level for at least 28 days; LBB269 (pBGH1)
      remained at a constant level in sterile water for at least 300 days. In non
      sterile water from both sources, the two strains declined from an initial
      concentration of about 3.0 x 10(6) cells per ml to less than 10 cells per ml in
      147 h. The study conditions did not adversely affect the populations of
      indigenous microorganisms. The selective loss of strains LBB269 and LBB269
      (pBGH1) demonstrates that these E. coli strains do not survive in environmental
      sources of water. In addition, it was observed that the presence of pBGH1 had
      essentially no effect on the disappearance of strain LBB269 from either source of
      water.

PMID- 1367976
TI  - Some factors influencing the proportion of periplasmic hepatitis B virus pre-S2
      antigen in the recombinant yeast Hansenula polymorpha.
AB  - A central composite design (CCD) was used to evaluate, for the purpose of future
      process optimization, the influence of pH, yeast extract and ammonium chloride
      concentrations on the proportion of periplasmic hepatitis B pre-S2 antigen in the
      recombinant yeast Hansenula polymorpha. Each factor was tested at five levels,
      and a second order polynomial model for the proportion of periplasmic antigen was
      fitted to the treatment combinations. pH showed the greatest effect: the
      proportion of periplasmic antigen was greatly increased at the higher pH levels.
      At the higher pH levels used, the proportion of periplasmic antigen was enhanced
      by a high concentration of ammonium chloride. Additional experiments have
      confirmed both the validity of the selected model and the optimal conditions
      found. A significant correlation was found between the proportion of periplasmic
      antigen and the total yield of antigen. These results indicated that it should be
      possible to modulate the distribution of the pre-S2 antigen between the periplasm
      and the cytoplasm of the yeast.

PMID- 1367977
TI  - Cloning and expression of the lysostaphin gene in Bacillus subtilis and
      Lactobacillus casei.
AB  - The lysostaphin structural gene was cloned in Bacillus subtilis DSM402 and in
      Lactobacillus casei 102S. The gene was expressed in both organisms and active
      lysostaphin was released into the medium. Lysostaphin produced by these organisms
      induced lysis of growing and heat inactivated staphylococci. Expression in a
      protective starter organism is a prerequisite to produce lysostaphin in situ in
      fermenting foods and hence, to reduce the hygienical risk of staphylococcal food
      poisoning.

PMID- 1367975
TI  - Detoxification of polycyclic aromatic hydrocarbons by fungi.
AB  - The polycyclic aromatic hydrocarbons (PAHs) are a group of hazardous
      environmental pollutants, many of which are acutely toxic, mutagenic, or
      carcinogenic. A diverse group of fungi, including Aspergillus ochraceus,
      Cunninghamella elegans, Phanerochaete chrysosporium, Saccharomyces cerevisiae,
      and Syncephalastrum racemosum, have the ability to oxidize PAHs. The PAHs
      anthracene, benz[a]anthracene, benzo[a]pyrene, fluoranthene, fluorene,
      naphthalene, phenanthrene, and pyrene, as well as several methyl-, nitro-, and
      fluoro-substituted PAHs, are metabolized by one or more of these fungi.
      Unsubstituted PAHs are oxidized initially to arene oxides, trans-dihydrodiols,
      phenols, quinones, and tetralones. Phenols and trans-dihydrodiols may be further
      metabolized, and thus detoxified, by conjugation with sulfate, glucuronic acid,
      glucose, or xylose. Although dihydrodiol epoxides and other mutagenic and
      carcinogenic compounds have been detected as minor fungal metabolites of a few
      PAHs, most transformations performed by fungi reduce the mutagenicity and thus
      detoxify the PAHs.

PMID- 1367978
TI  - Determination of a "critical shear stress level" applied to adherent mammalian
      cells.
AB  - An apparatus for the detailed investigation of the influence of shear stress on
      adherent BHK cells was developed. Shear forces between 0.0 and 2.5 N m-2 were
      studied. The influence on cell viability, cell morphology, cell lysis, and cell
      size was determined. Increasing shear forces as well as increasing exposure
      duration caused increasing changes in cell morphology and cell death. A "critical
      shear stress level" was determined.

PMID- 1367979
TI  - Development of a piezoelectric immunosensor for the detection of enterobacteria.
AB  - A piezoelectric crystal immunosensor has been developed for the detection of
      enterobacteria in drinking water using antibodies against the enterobacterial
      common antigen. Applying an anti-enterobacterial antibody layer via protein A
      immobilization onto a 10-MHz crystal, a response is observed for 10(6) to 10(9)
      cells ml-1 of Escherichia coli K12, and for various other antigens of the
      Enterobacteriaceae family.

PMID- 1367980
TI  - Evidence for posttranscriptional stimulation of monoclonal antibody secretion by
      L-glutamine during slow hybridoma growth.
AB  - The addition of 5-40 mM L-glutamine to batch cultures of a murine hybridoma
      following the cessation of rapid growth significantly stimulated monoclonal
      antibody (mAb) synthesis and secretion per cell. Stimulation of mAb secretion
      following the cessation of rapid growth was also observed in response to addition
      of mitochondrial intermediates of glutamate oxidation and was not found to be the
      result of release of transiently stored mAb. Less than 1% of the secreted mAb was
      detected by ELISA in isolated hybridoma lysosomes. This stimulation was
      posttranscriptional and not the result of enhancement of levels of mAb mRNAs or
      stabilization of heavy (H) or light (L) chain encoding message. Sub-inhibitory
      levels of lysosomotrophic weak bases stimulated release of lysosomal contents but
      did not result in release of intact or partially degraded mAb. Inhibition of
      aspartic proteinase activity secreted by the hybridoma did not enhance mAb
      secretion even though a high level of mAb degrading proteinase activity was
      continuously secreted during both rapid and slow growth. These responses indicate
      that during slow growth, the addition of L-glutamine increases the availability
      of cellular ATP generated by mitochondrial respiration which stimulates some
      posttranscriptional step in the pathway of mAb secretion such as the rate of H or
      L chain translation, chain assembly, interorganelle transport or vesicular
      transport from the Golgi to the cell membrane.

PMID- 1367981
TI  - Some recent developments in the use of enzyme catalysed reactions in organic
      synthesis.
AB  - The following processes are discussed in this article: enzyme-catalysed
      hydrolyses of carboxylic acid esters and amides, phosphate esters, nitriles and
      epoxides; esterification and inter-esterification reactions catalysed by enzymes;
      reduction of ketones to secondary alcohols using whole-cell systems or isolated
      dehydrogenases; oxidation of alicyclic and aromatic substrates using mono
      oxygenases and dioxygenases in bacteria and fungi including enzyme-catalysed
      Baeyer-Villiger oxidations; aldol reactions, formation of optically active
      cyanohydrins and enzyme-catalysed acyloin type reactions. The use of these
      biocatalytic methods for the stereo-controlled preparation of important target
      structures is reviewed and some of the future directions for the
      biotransformation area are discussed.

PMID- 1367982
TI  - Further studies of the culture of mouse hybridomas in an agitated bioreactor with
      and without continuous sparging.
AB  - TB/C3 mouse hybridoma cells have been grown at 2 controlled dO2 conditions by
      headspace and sparged oxygenation. Also a variety of sparging rates and sparger
      sizes and positions have been employed. Headspace oxygenation at dO2 levels from
      5% to 100% of saturation give essentially the same performance as controls.
      Sparging is generally damaging to cells, the extent of damage decreasing with
      reduced sparging rate until at below about 0.02 vvm results equivalent to the
      unsparged conditions are obtained. Damage is clearly linked with bubble-cell
      interactions at the air-medium interface where bubbles bursting in clusters and
      of a size less than 5 mm appear to be the most lethal. When the interaction of
      air sparging with the agitator flow leads to an increase in the number of smaller
      bubbles and cluster bursts, cell damage is further increased. Pluronic F-68
      reduces damage very significantly. Biological aspects are briefly discussed in
      the light of various biological tests. The practical implications of this work
      for large scale, free suspension cell culture are outlined.

PMID- 1367983
TI  - High-level expression of staphylococcal nuclease R gene in Escherichia coli.
AB  - Staphylococcal nuclease R, an analogue of nuclease A, was overproduced under the
      transcriptional control of the bacteriophage lambda PRPL promoters regulated by
      temperature sensitive repressors. The expression level reached 200-300 mg l-1 and
      showed little host dependence in different strains. The investigations of the
      recombinant nuclease R have revealed that the amino terminal formyl methionine
      residue of the nuclease is precisely processed, the protein consists of 155 amino
      acid residues. The experiment shows that the pBV221-DH5 alpha is a quite suitable
      vector-host system for high-level expression and precise processing of
      heterologous genes in Escherichia coli. The comparative studies between the
      codons used in the staphylococcal nuclease R gene and the optimal codon usage in
      E. coli indicate that high level expression of heterologous genes in E. coli may
      not always require a high degree of codon usage bias.

PMID- 1367984
TI  - A CHO strain producing high-level human IL-6 with the 3' deletion construct.
AB  - A Chinese Hamster Ovary (CHO) strain producing high-level human interleukin 6 (IL
      6) was obtained, by introduction of the IL-6 cDNA from which the 3' AU-rich
      region was deleted. The IL-6 mRNA of this strain was stable. The productivity was
      more than 15 times higher than the previously obtained clone, which has intact IL
      6 cDNA in the same expression vector. This strain produced IL-6 at a high level
      of 30 micrograms ml-1 in batch culture, or a continuous 20 micrograms per 10(6)
      cells per day in microcarrier cultivation.

PMID- 1367985
TI  - Continuous beta-galactosidase production with a recombinant baculovirus insect
      cell system in bioreactors.
AB  - Insect cells were exploited to produce bacterial beta-galactosidase by infecting
      them with a recombinant nuclear polyhedrosis virus (baculovirus) of Autographa
      californica. The insect cells were cultured in a continuous stirred tank reactor
      (CSTR) and led to a second CSTR where they were infected with a recombinant virus
      in which the lacZ gene from Escherichia coli was inserted. In the effluent of the
      production reactor, maximum activities of 15 units beta-galactosidase per 10(6)
      cells were measured. For about 25 d beta-galactosidase production remained
      constant, but then rapidly declined. This drop was due to a decrease in
      production of active beta-galactosidase rather than to inactivation of this
      enzyme. It was concluded that the reduced production was due to reduced
      polyhedrin promoter-driven synthesis.

PMID- 1367986
TI  - Cloning and high level expression of a synthetic gene for human basic fibroblast
      growth factor.
AB  - A gene encoding human basic fibroblast growth factor has been chemically
      synthesized, cloned and expressed in Escherichia coli as a biologically active
      protein. The 465 bp gene was assembled by enzymatic ligation of 6 pairs of
      oligonucleotides and cloned in the expression vector pLCII downstream from the
      strong PL promoter. This promoter directed the synthesis of a fusion protein
      between a 31 amino acids fragment of the lambda phage cII protein and bFGF. A
      four amino acid recognition sequence for the site-specific protease fXa was
      introduced in the plasmid construct and this allowed cleavage of the fusion
      protein at the boundary between cII and bFGF. bFGF was purified close to
      homogeneity using a Heparin-Sepharose column and Mono S cation exchange
      chromatography. The use of the pLCII expression system resulted in the
      accumulation of 20 to 25 mg of purified bFGF per l of bacterial culture. The
      recombinant bFGF was mitogenic for mouse 3T3 fibroblasts and the dose-response
      curve was similar to the one for native bFGF.

PMID- 1367987
TI  - Cultivation of animal cells in a reticulated vitreous carbon foam.
AB  - A reticulated vitreous carbon foam (RVCF) was used as a surface to cultivate a
      model anchorage-dependent animal cell line, 3T6 (mouse embryo fibroblast). This
      fixed-surface bioreactor provided a low-shear, chemically-inert, and reusable
      environment for cell growth. An external medium recirculation loop allowed
      aeration, nutrient monitoring, and medium replacement without disturbing the
      cells. Optimal flow rates for the attachment and growth phases were determined.
      Growth rates comparable to static (T-flask and petri dish) cultures and agitated
      microcarrier cultures were achieved with appropriately high medium recirculation
      rates. Metabolic parameters were shown to be useful indicators of cell mass,
      although specific glucose consumption rates were considerably higher for cultures
      in the RVCF reactor. Oxygen supply was shown to be the most likely limiting
      factor for scaleup.

PMID- 1367988
TI  - The decisive role of the Saccharomyces cerevisiae cell cycle behaviour for
      dynamic growth characterization.
AB  - The dynamic behaviour of the cell cycle and the physiology of Saccharomyces
      cerevisiae was monitored in transient experiments. Frequent flow cytometric
      analyses of the DNA (nuclear phase state) and the cell size enabled us to
      characterize the proliferation properties of yeast cells under well controlled
      and undisturbed cultivation conditions. Preliminarily, the correlation between
      flow cytometric light scattering measurements and the cell size was attested for
      yeasts. These flow cytometric results are compared with the physiological
      behaviour of the culture that was detected by high resolution on-line analyses
      and off-line measurements. The presented results focus on the importance of the
      yeast cell cycle behaviour for the dynamic growth characterization. Any kind of
      transients in yeast cultures induced partial synchronization. The characteristics
      and the time course of the yeast cell cycle were found to be strongly dependent
      on the physiological environment.

PMID- 1367989
TI  - Factors influencing expression and post-translational modification of recombinant
      protein C.
AB  - Factors affecting the production of recombinant human protein C were
      investigated. When recombinant cells producing human protein C were cultured with
      microcarrier in two different scales, we found that (1) as cells grew to
      confluence, specific productivity of the protein was decreased and that (2) the
      efficiency of gamma-carboxylation of the generated protein C was lower in a
      larger culture than in a smaller culture. Higher cell density was shown to
      influence the specific productivity unfavorably. On the other hand, the amount of
      oxygen supply as demonstrated by oxygen consumption rate in the Opticell culture
      system correlated well with the efficiency of gamma-carboxylation, suggesting
      that oxygen metabolism is somehow implicated in the post-translational
      modification of recombinant protein C.

PMID- 1367990
TI  - Immobilization of Arthrobacter simplex in thermally reversible hydrogels: effect
      of gel hydrophobicity on steroid conversion.
AB  - Arthrobacter simplex cells have been immobilized in a series of thermally
      reversible hydrogels having different gel hydrophobicities. Steroid conversion
      from hydrocortisone to prednisolone via the delta 1-dehydrogenase system was
      greatly affected by the relative hydrophobicities of the gel matrices, which were
      prepared by copolymerizing varying ratios of N-isopropylacrylamide to acrylamide.
      The characteristics of the immobilized cells, such as optimal temperatures, Km
      values, and the effects of an added artificial electron acceptor, were largely
      influenced by the gel matrices and their different lower critical solution
      temperatures (LCST). The data indicate that the microenvironment of the
      dehydrogenation system is quite different within the different
      hydrophilic/hydrophobic gel matrices. The high partitioning of water-insoluble
      steroids into the hydrophobic regions and the reduced possibility of product
      inhibition within the more hydrophobic gel matrices may cause the observed higher
      steroid conversion in these gels. A possible model for immobilized A. simplex
      cells in such different gel matrices is proposed.

PMID- 1367991
TI  - Isolation of human B-cell subpopulations for pharmacological studies.
AB  - Three groups of human peripheral blood B-lymphocytes were separated from each
      other by countercurrent centrifugal elutriation and free-flow electrophoresis.
      They differed in their state of maturation and in their capability to produce
      antibodies in vitro. These B-cell subpopulations were used to study features of a
      drug such as BAY R 1005. BAY R 1005 is a synthetic glycolipid analogue (GLA),
      which is supposed to modulate antibody synthesis. Mature, immunoglobulin- (Ig-)
      secreting B-lymphocytes secreted equal quantities of antibodies in the presence
      and in the absence of the GLA. BAY R 1005 was found to be without mitogenic
      activity on resting B-cells and did not induce them to produce antibodies.
      However, it supported the antibody production of preactivated B-lymphocytes. The
      in vitro preactivated B-cells were affected via monocytes. Only in vivo
      preactivated B-lymphocytes increased their antibody production under the direct
      influence of BAY R 1005.

PMID- 1367992
TI  - Adsorption characteristics of an immobilized metal affinity membrane.
AB  - An immobilized metal affinity (IMA) hollow-fiber membrane was prepared by
      radiation-induced graft polymerization of glycidyl methacrylate (GMA) onto a
      porous polyethylene hollow fiber, followed by chemical conversion of the produced
      epoxide group into an iminodiacetate (IDA) group and its chelation with
      copper(II) ion. The IDA hollow fiber, whose degree of GMA grafting was 120%, was
      found to retain 0.42 mol of Cu ion/kg of dry weight of the resulting IMA hollow
      fiber. The pure water flux of the affinity membrane was 0.90 m/h at a filtration
      pressure of 1 x 10(5) Pa. The 0.1 g/L L-histidyl-L-leucine (His-Leu) solution
      permeated across the IMA hollow fiber, whose inner diameter and thickness were
      0.78 and 0.365 mm, respectively, at a prescribed filtration pressure ranging from
      0.2 x 10(5) to 1.0 x 10(5) Pa. The adsorption of His-Leu during permeation of the
      solution showed that the overall adsorption rate was independent of the
      filtration pressure, i.e., the residence time, because of the negligible
      diffusional resistance of His-Leu to the pseudobioaffinity ligand located on the
      pore surface of the membrane. No deterioration in the adsorption capacity was
      observed after five cycles of His-Leu adsorption, its elution, and
      reimmobilization of copper. The adsorption isotherm of bovine serum albumin (BSA)
      on the IMA hollow fiber was measured and compared with that for the conventional
      agarose-based bead containing the IDA-Cu ligand.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1367993
TI  - Manipulation of heterogeneous hybridoma cultures for overproduction of monoclonal
      antibodies.
AB  - In searching for ways to manipulate heterogeneous hybridoma cell cultures (ATCC
      HB124) to obtain increased production of monoclonal antibodies (IgG2a), we have
      selected for a higher secreting but slower growing subpopulation using the level
      of fluorescent surface-associated antibodies and a fluorescence-activated cell
      sorter. Cell surface fluorescence was found to be correlated with specific
      antibody secretion rate over the short term but not with intracellular antibody
      content. Also, the specific secretion rate of a heterogeneous population of
      hybridoma cells grown in batch culture has been shown to be inversely correlated
      with an increase in either the initial cell concentration or the medium antibody
      concentration. Several experiments suggest that an upper limit exists for medium
      antibody concentration, above which antibody is degraded at the same rate at
      which it is produced. Should other cell lines behave similarly, strategies for
      overproduction of monoclonal antibodies suggested herein could be profitably used
      in industry.

PMID- 1367994
TI  - Evaluation of immunoglobulins from plant cells.
AB  - Expression of cDNA constructs encoding full-length mouse immunoglobulin chains
      with their native leader sequences or fusion constructs substituting the native
      leader with a pre-pro sequence derived from Saccharomyces cerevisiae yielded
      blocked N-termini on the gamma chain or the correct amino terminal sequence on
      the mature kappa chain. Lectin binding assays revealed that assembled
      immunoglobulin complexes contained a glycosylated heavy chain. The attached
      glycan was resistant to digestion by endoglycosidase H and its lectin binding
      pattern was distinguishable from that of the mammalian glycan. The results
      indicated processing of the immunoglobulin carbohydrate in the tobacco Golgi to
      yield a complex oligosaccharide. Secretion of antibody by protoplasts isolated
      from regenerated transgenic plants or from suspension callus cells was
      demonstrated by pulse-chase labeling experiments. When purified, the tobacco
      produced antibody was found to possess the antigen binding and catalytic
      properties of the murine monoclonal antibody. Kinetic parameters (Km, Ki, Vmax,
      and kcat) of the tobacco-derived antibody were comparable to those of the mouse
      derived antibody. The results in general show that the endomembrane system of
      tobacco cells possesses cognate mechanisms for the recognition of diverse leader
      sequences. These signals can be used to initiate the assembly, processing, and
      secretion by plant cells of complex foreign proteins.

PMID- 1367995
TI  - Production of recombinant proteins by baculovirus-infected gypsy moth cells.
AB  - An experimental study was undertaken to evaluate alternative insect cell lines to
      Sf9 [from Spodoptera frugiperda (fall armyworm)] for the production of
      recombinant proteins. Insect cell lines from two different organisms were
      considered: IPLB-LdEIta (LdEIta) from Lymantria dispar (gypsy moth) and IPLB-HvT1
      (HvT1) from Heliothis virescens (tobacco budworm). Both LdEIta and HvT1 produced
      higher total activity levels of recombinant beta-galactosidase in monolayer
      culture than Sf9 after infection with the Autographa californica nuclear
      polyhedrosis virus (AcMNPV). However, only LdEIta generated a product yield
      (activity per milligram of total protein) which exceeded that of Sf9 (by 25%), so
      its growth and production characteristics were investigated in depth. LdEIta
      generated production levels and yields of a recombinant rotaviral protein, VP4,
      which exceeded those of Sf9 by 84 and 38%, respectively. In suspension culture,
      the LdEIta cells grew as aggregates with a doubling time several hours longer
      than Sf9, but the recombinant product yields of LdEIta were still higher than Sf9
      by 38% in this culture environment. beta-Galactosidase expression rates and cell
      death rates suggested that the difference in productivity between the two hosts
      was due to the ability of LdEIta to survive the baculovirus infection and produce
      recombinant proteins longer than Sf9. The presence of LdEIta aggregates in
      suspension culture may be used as a method to separate live cells from dead
      cells, labile product, and spent medium in recombinant protein production
      processes.

PMID- 1367996
TI  - Polyethyleneimine in immobilization of biocatalysts.
AB  - A variety of polymers with amino pendant groups have been accepted as suitable
      enzyme carriers. A number of synthesis strategies and techniques are adopted to
      anchor enzymes. The polymers are activated through derivatization either prior to
      or during adsorption to facilitate the covalent binding of enzyme.
      Polyethyleneimine (PEI), with the highest concentration of amino groups, has
      found acceptance as a carrier in a number of industrial immobilized biosystems.
      The two forms of PEI known are the linear crystalline type and the more important
      amorphous branched structure with a distribution of primary, secondary, and
      tertiary amino groups in the ratio 1:2:1. The primary and secondary amino groups
      are conveniently modified to generate facile enzyme carriers. A number of patents
      have been filed on the use of PEI to bind a rich variety of enzymes and whole
      cells. This review is primarily a compilation of these reports and purports to
      highlight the potential of PEI.

PMID- 1367997
TI  - Continuous delta 1-hydrocortisone dehydrogenation with in situ product recovery.
AB  - A continuous aerated process for delta 1-hydrocortisone dehydrogenation by
      polyacrylamide-hydrazide (PAAH) bead-entrapped A. simplex cells was developed.
      The process allows for stable conversion of 1.6 g l-1 hydrocortisone (x 5 the
      solubility in water), made possible by the incorporation of selected cosolvent
      [5% (v/v) triethyleneglycol]. A large difference in substrate and product
      solubilities in the cosolvent-buffer medium allowed for in situ product recovery
      in an aerated, fluidized-bed, immobilized-cell reactor by the controlled addition
      of fine product-adsorbing powder (microcrystalline cellulose). The product was
      recovered at the reactor outlet as a fine complex with the adsorbent. Stable
      continuous operation of at least 4 weeks was recorded for a prototype reactor
      configuration, followed by the exhibition of similar operational stability in a
      modified version of a commercially available 2.5-l airlift reactor. Our results
      demonstrate that in addition to an obvious desirable cosolvent effect on
      substrate solubility enhancement, it may also enable easy in situ product
      recovery by creating a large gap in the solubilities of the substrate and the
      product in the cosolvent-containing reaction medium.

PMID- 1367998
TI  - Metabolism of hybridoma cells and antibody secretion at high cell densities in
      dialysis tubing.
AB  - The experimental setup, consisting of a bundle of dialysis tubing 2.5 mm in
      diameter [10-15 kD cutoff, mean pore size 25 A, 20 microns (dry) and 40 microns
      (wet) wall thickness] inserted into a 1-l glass bioreactor supplied with oxygen
      and pH electrodes, a porous gas distributor, a sampling tube, and a holder for
      the eight pieces of dialysis tubing, was developed to investigate the properties
      and the microenvironment of hybridoma cells enclosed in the tubing during their
      batch cultivation. The concentrations of low-molecular-weight medium components
      were the same inside and outside the tubing, and it was possible to control the
      microenvironment of the cells in the tubing easily. The cell damage caused by
      mechanical stress was less in the dialysis tubing than in stirred spinner flasks.
      The influence of the initial cell density in the range from 4 X 10(5) to 1 X
      10(8) cells ml-1 and the cultivation time were evaluated according to the total
      and viable cell concentrations and the cell/cell fragment size distributions.
      Furthermore, the cell membrane properties, glucose consumption rate, lactate,
      ammonia and lipid storage material, and the monoclonal antibody production rates
      as well as intracellular enzyme activities in the culture medium were measured
      and compared to those in reference cultures in spinner flasks with the same
      inoculum at low initial cell densities. In dialysis tubing in a concentration
      range of 5 X 10(6) to 10(8) cells ml-1, the total and viable concentrations of
      cells remained the same during cultivation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1367999
TI  - Large-scale (20 l) culture of surface-immobilized Catharanthus roseus cells.
AB  - Surface-immobilized C. roseus cell cultures were grown in a 20-l modified airlift
      bioreactor operated at 0.51 vvm (kLa approximately 8 h-1) under various gassing
      regimes [air, 2% (v/v) and 5% CO2]. Extracellular ammonium, phosphate, and
      nitrate ions as well as carbohydrate uptake and pH value of the medium were
      monitored together with on-line dissolved oxygen concentration, conductivity of
      the medium, and carbon dioxide production rate (CPR) of the cultures. Cultures
      supplemented with 2% CO2 showed higher nitrate (5.0-7.0 mM d-1) and carbohydrate
      (3.3 g l-1 d-1) uptake rates and biomass production (mu approximately 0.24 d-1,
      yield approximately 0.33 g dw g CHO-1 and 7.4 g dw L-1) as compared to air (3.6
      mM d-1, 2.1 g l-1 d-1; 0.20 d-1, 0.25 g dw g CHO-1 and 5 g dw l-1) and 5% CO2
      (2.0-3.6 mM d-1, 2.0 g l-1 d-1; 0.11 d-1, 0.20 g dw g CHO-1 and 5 g dw l-1)
      cultures and as reported previously for suspension cultures. In addition, air and
      5% CO2 cultures displayed incomplete carbohydrate uptake and, more important,
      phosphate and ammonium ion release into the medium at the end, which was ascribed
      to loss of viability. This was not observed for 2% CO2 immobilized bioreactor as
      well as shake flask control suspension cultures, which suggests that sparged C.
      roseus surface-immobilized cell cultures require 2% CO2 supplementation of the
      gas phase for both maximum growth and retained viability. The maximum CPRs of all
      cultures were in the same range (2.1-2.8 mM CO2 l-1 h-1). However, the estimated
      maximum specific CO2 production rates of 2% CO2 and 5% CO2 immobilized cultures
      (0.6 mM g dw-1 h-1) were lower than those found for air-sparged immobilized
      cultures (1.0-1.3 mM g dw-1 h-1). These rates are significantly higher than those
      reported in the literature for C. roseus cell suspension cultures performed in
      bioreactors gassed with air (approximately 0.2-0.55 mM g dw-1 h-1).

PMID- 1368000
TI  - Enzyme reaction engineering: synthesis of antibiotics catalysed by stabilized
      penicillin G acylase in the presence of organic cosolvents.
AB  - By using very active and very stable penicillin G acylase (PGA)--agarose
      derivatives we have studied the industrial design of equilibrium-controlled
      synthesis of lactamic antibiotics. In the presence of high concentrations of
      organic cosolvents we have carried out the direct enzymatic condensation of
      phenylacetic acid and 6-aminopenicillanic acid to yield the model antibiotic
      penicillin G. We have mainly studied the integrated effect of different variables
      that define the reaction medium on a number of parameters of industrial
      interest:time course of antibiotic synthesis, highest synthetic yields, stability
      of the catalyst, and solubility and stability of substrates and products. The
      main variables tested were the nature and concentration of the organic cosolvent,
      pH, and temperature. The effects of the variables tested on different parameters
      were quite different and sometimes opposite. Hence, the optimal experimental
      conditions for antibiotic synthesis catalysed by PGA were established, as a
      compromise solution, in order to obtain good values for every parameter of
      industrial interest. These conditions seem to be important parameters for scale
      up (e.g. we have been able to reach more than 95% of synthetic yields with
      productivities around 0.5 tons of model antibiotic per year per liter of
      catalyst).

PMID- 1368001
TI  - Stereospecific microbial reduction of 4,5-dihydro-4-(4-methoxyphenyl)-6
      (trifluoromethyl-1H-1)-benzazepin+ ++-2-o ne.
AB  - A key intermediate, (3R-cis)-1,3,4,5-tetrahydro-3-hydroxy-4-(4-methoxyphenyl)-6
      (trifluorome thyl)- 2H-1-benzazepin-2-one (compound II or SQ32191), with high
      optical purity was made by the stereoselective microbial reduction of the parent
      ketone 1. Several strains of bacterial and yeast cultures were screened for the
      ability to catalyse the stereoselective reduction of 4,5-dihydro-4-(4
      methoxyphenyl)-6-(trifluoromethyl)-1H-1-benzazepin++ +-2,3-dione [compound I or
      SQ32425]. Microorganisms from the genera Nocardia, Rhodococcus, Alkaligenes,
      Corynebacterium, Arthrobacter, Hansenula, and Candida reduced compound I to
      compound II with 60-70% conversion yield. In contrast, microorganisms from the
      genera Pseudomonas and Acinetobacter reduced compound I stereospecifically to
      (trans)-1,3,4,5-tetrahydro-3-hydroxy-4-(4-methoxyphenyl)-6-(trifluoromet hyl-2H-
      1-benzazepin-2-one (compound III or SQ32408). Among various cultures evaluated,
      N. salmonicolor SC6310 effectively catalysed the transformation of compound I to
      compound II with 96% conversion yield at 1.5-2.0 gl-1 concentration. Compound II
      was isolated and identified by NMR analysis, mass spectrometry, and comparison to
      an authentic sample. Preparative scale fermentation process and transformation
      process were developed using cell suspensions of N. salmonicolor SC6310 to
      catalyse the transformation of compound I to compound II. The isolated compound
      II had a melting point of 222 degrees C (reference 221-223 degrees C), optical
      rotation of +130.4 (reference +128 degrees C), and optical purity of greater than
      99.9% as analyzed by NMR and chiral HPLC.

PMID- 1368002
TI  - Biological responses of hybridoma cells to hydrodynamic shear in an agitated
      bioreactor.
AB  - Effects of long-term hydrodynamic shear on hybridoma cells were investigated in a
      250-ml continuous stirred-tank reactor (CSTR). Cells grown at steady state were
      subjected to step changes in agitation rates. Cell viability, glucose
      consumption, and monoclonal antibody (MAb) production were determined at high
      agitation rates and compared with the control (100 rev min-1). Impeller tip
      speeds higher than 40 cm s-1 caused a significant drop in cell concentration and
      respiration activity, and increased lactate dehydrogenase (LDH) release to the
      culture medium. Also, high agitation speeds caused a decrease in MAb
      concentration and an increase in specific glucose consumption rate. The effects
      of dilution rate and serum concentration on the sensitivity of hybridoma cells to
      hydrodynamic shear were determined. Serum was found to protect the cells against
      shear damage and had a significant positive effect on hybridoma growth and MAb
      production. Shear damage on cells in CSTR was approximated to first-order
      kinetics. The death rate constant increased sharply at impeller tip speeds above
      40 cm s-1.

PMID- 1368003
TI  - Effect of immobilisation on the production of alpha-amylase by an industrial
      strain of Bacillus amyloliquefaciens.
AB  - The effect of immobilisation of an industrial strain of Bacillus
      amyloliquefaciens in calcium alginate beads on production of alpha-amylase was
      investigated using lactose-based media in shake flasks and in a 0.3 dm3 glass
      fermenter. Although the microorganism was a good alpha-amylase producer in batch
      cultures of free cells, it was unable to produce the enzyme for extended periods
      either in repeated batch cultures, or in continuous cultivation. In each case,
      parallel tests with cells immobilised in calcium alginate beads gave still
      further reduced enzyme yields, and the free cells released into the broth from
      these beads probably contributed substantially to any amylase produced during
      these extended fermentations. After prolonged use, the core of the alginate beads
      accumulated hard insoluble material, with viable immobilised cells confined to a
      surface layer.

PMID- 1368004
TI  - The extraction of penicillin G with aliphatic amines in organic solvents of
      different polarities.
AB  - The equilibrium constants of the extraction, the molar ratios of amines to
      penicillin G in the extract and the bonding structures of the extracted species
      were studied with chemical analysis and the absorbance shift of FT-IR spectra of
      the functional groups in penicillin G. Extraction of penicillin G from the
      filtrate of fermentation broth indicates that amines will be difficult to use as
      the industrial solvent for the production of penicillin G because of the poor
      quality of the final crystalline product obtained and the difficulties involved
      in the stripping and solvent recovery.

PMID- 1368005
TI  - Effective diffusivity of galactose in calcium alginate gels containing
      immobilized Zymomonas mobilis.
AB  - The effective diffusivity of galactose was measured for calcium alginate gel
      membranes containing immobilized live Zymomonas mobilis cells at concentrations
      ranging from 0 to 150 g dry wt/L of gel. Since galactose is not taken up by
      living Z. mobilis organisms, the diffusion of this representative six-carbon
      sugar could be studied independently of sugar consumption. Various immobilized
      biomass loadings were achieved by two different techniques: addition of biomass
      at known concentrations to the sodium alginate solution before membrane formation
      and growth of cells in the gel to various biomass concentrations. The highest
      immobilized cell concentration, attained by in situ growth, corresponds to the
      maximum of this system, as growth beyond this maximum concentration led to
      disintegration of the gel membrane. The galactose effective diffusivity
      measurements for both methods of immobilized cell loading overlap within
      experimental error and follow the same general monotonic decline with entrapped
      biomass concentration. Most of the data fall below the upper bound predicted by
      Hashin and Shtrikman (1962) and show good agreement with the random pore model of
      Wakao and Smith (1962, 1964). Available effective diffusivity data from the
      literature provide evidence that the random pore model is an excellent predictor
      of sugar effective diffusivity in gel immobilized cell systems in general.

PMID- 1368006
TI  - Mathematical model for the effects of epidermal growth factor receptor
      trafficking dynamics on fibroblast proliferation responses.
AB  - We apply a mathematical model for receptor-mediated cell uptake and processing of
      epidermal growth factor (EGF) to analyze and predict proliferation responses to
      fibroblastic cells transfected with various forms of the EGF receptor (EGFR) to
      EGF. The underlying conceptual hypothesis is that the mitogenic signal generated
      by EGF/EGFR binding on the cell surface, via stimulation of receptor tyrosine
      kinase activity, is attenuated when the receptors are downregulated and growth
      factor is depleted by endocytic internalization and subsequent intracellular
      degradation. Hence, the cell proliferation rate ought to depend on
      receptor/ligand binding and trafficking parameters as well as on intrinsic
      receptor signal transduction properties. The goal of our modeling efforts is to
      formulate this hypothesis in quantitative terms. The mathematical model consists
      of kinetic equations for binding, internalization, degradation, and recycling of
      EGF and EGFR, along with an expression relating DNA synthesis rate to EGF/EGFR
      complex levels. Parameter values have been previously determined from independent
      binding and trafficking kinetic experiments on B82 fibroblasts transfected with
      wild-type and mutant EGFR. We show that this model can successfully interpret
      literature data for EGF-dependent growth of NR6 fibroblasts transfected with wild
      type EGFR. Moreover, it successfully predicts the literature observation that NR6
      cells transfected with a delta 973 truncation mutant EGFR, which is kinase-active
      but internalization-deficient, require an order of magnitude lower EGF
      concentration than cells with wild-type EGFR for half-maximal proliferation rate.
      This result demonstrates that it may be feasible to genetically engineer
      mammalian cell lines with reduced growth factor requirements by a rational,
      nonempirical approach. We explore by further model computations the possibility
      of exploiting other varieties of EGFR mutants to alter growth properties of
      fibroblastic cells, based on relationships between changes in the primary
      structure of the EGF receptor and the rates of specific receptor/ligand binding
      and trafficking processes. Our studies show that the ability to predict cell
      proliferation as a function of serum growth factors such as EGF could lead to the
      designed development of cells with optimized growth responses. This approach may
      also aid in elucidation of mechanisms underlying loss of normal cell
      proliferation control in malignant transformation, by demonstrating that receptor
      trafficking dynamics may in some cases play as important a role as intrinsic
      signal transduction in determining the overall resulting mitogenic response.

PMID- 1368007
TI  - Micropatterning proteins and synthetic peptides on solid supports: a novel
      application for microelectronics fabrication technology.
AB  - In this paper, we describe a method for immobilizing proteins and synthesizing
      peptides in micrometer-dimension patterns on solid supports. Microelectronics
      fabrication technology was adapted and used to lithographically direct the
      location of immobilization of proteins on appropriately derivatized surfaces. As
      examples, we micropatterned the protein bovine serum albumin (BSA) and the enzyme
      horseradish peroxidase (HRP). The catalytic activity of HRP was shown to be
      retained after being cross-linked to the support. When coupled with solid-phase
      peptide synthesis, the technique allowed synthetic peptides to be constructed in
      patterns again having micrometer dimensions. Synthetic polypeptides, polylysine,
      were constructed in patterns with dimensions that approached the practical limit
      of resolution for optical lithography at 1-2 microns. The patterns of immobilized
      molecules and synthetic peptides were visualized using histochemical methods
      together with light and fluorescence microscopy. The protein and peptide
      patterning technique described here is an advance in the field of bioelectronics.
      In particular, it should now be possible to devise novel methods for interfacing
      with biological systems and constructing new devices for incorporation into
      miniaturized biosensors.

PMID- 1368008
TI  - An improved method for disruption of microbial cells with pressurized carbon
      dioxide.
AB  - Disruption of microbial cells by pressurized carbon dioxide at both subcritical
      and supercritical temperatures has been previously investigated. This method
      differs in principle from other disruption techniques and was found to have
      potential applications for rupture of a variety of microorganisms. However, it is
      not as effective for some of the microbial cells, including yeast, of which the
      cell walls are extremely robust and rigid. This work suggests an alternative
      operation to improve the disruption rates of cells by repeatedly releasing the
      applied fluid pressure within the cells in the midst of a disruption process. The
      improvement is substantial at all the experimental conditions studied.

PMID- 1368009
TI  - Transient association of the first intermediate during the refolding of bovine
      carbonic anhydrase B.
AB  - Many proteins which aggregate during refolding may form transiently populated
      aggregated states which do not reduce the final recovery of active species.
      However, the transient association of a folding intermediate will result in
      reduced refolding rates if the dissociation process occurs slowly. Previous
      studies on the refolding and aggregation of bovine carbonic anhydrase B (CAB)
      have shown that the molten globule first intermediate on the CAB folding pathway
      will form dimers and trimers prior to the formation of large aggregates (Cleland,
      J. L.; Wang, D. I. C. Biochemistry 1990, 29, 11072-11078; Cleland, J. L.; Wang,
      D. I. C. In Protein Refolding; Georgiou, G., De-Bernardez-Clark, E., Eds.; ACS
      Symposium Series 470; American Chemical Society: Washington, DC, 1991; pp 169
      179). Refolding of CAB from 5 M guanidine hydrochloride (GuHCl) was achieved at
      conditions ([CAB]f = 10-33 microM, [GuHCl]f = 1.0 M) which allowed complete
      recovery of active protein as well as the formation of a transiently populated
      dimer of the molten globule intermediate on the refolding pathway. A kinetic
      analysis of CAB refolding provided insight into the mechanism of the association
      phenomenon. Using the kinetic results, a model of the refolding with transient
      association was constructed. By adjusting a single variable, the dimer
      dissociation rate constant, the model prediction fit both the experimentally
      determined active protein and dimer concentrations. The model developed in this
      analysis should also be applicable to the refolding of proteins which have been
      observed to form aggregates during refolding. In particular, the transient
      association of hydrophobic folding intermediates may also occur during the
      refolding of other proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1368010
TI  - Synthesis and anti-inflammatory activity of some novel 1,3,4-oxadiazole
      derivatives.
AB  - Some novel 1,3,4-oxadiazoline and 1,3,4-oxadiazole derivatives have been
      synthesized from 3-hydroxy-5,6-diphenyl-1,2,4-triazine. Illucidation of the
      structures of the isolated products has been proved in the light of their
      elemental analysis, spectroscopic data and unambiguous synthesis in certain
      cases. Some derivatives have shown promising anti-inflammatory activity in
      comparison to phenylbutazone.

PMID- 1368011
TI  - Kinetics and stability of a Chromobacterium viscosum lipase in reversed micellar
      and aqueous media.
AB  - The lipolytic activity of Chromobacterium viscosum lipase B (EC 3.1.1.3.;
      triacylglycerol hydrolase) solubilized both in water and AOT/isooctane reversed
      micelles has been investigated using triolein as a substrate. The influence of
      relevant parameters in the catalytic activity such as temperature, pH, surfactant
      and substrate concentrations, and water content was tested and compared in both
      media. A study of stability of the lipase was carried out, with particular
      reference to the influence of pH. Three major effects of the encapsulation of the
      lipase in the micelles were observed: increased activity (up to 7 times higher
      than in water), greater stability, specially at pH 7, and higher resistance to
      thermal deactivation.

PMID- 1368012
TI  - Stability of Lactobacillus bulgaricus immobilized in kappa-carrageenan gels.
AB  - The future application of immobilized microorganism techniques will depend on the
      development of systems which are technologically applicable on an industrial
      scale. These techniques must permit high microbial concentrations and must allow
      mass transfer to take place with low diffusional limitations. In addition, the
      mechanical separation of the immobilized microorganisms must be achieved
      economically. Kappa-carrageenan was used as an ionotropic gel carrier for the
      immobilization of Lactobacillus bulgaricus (ATCC 11842), and the effects of gel
      stability on productivity and the rate of product formation were investigated.
      kappa-carrageenan gels had higher mechanical and chemical stability than alginate
      gels. The storage stability of microorganisms immobilized in kappa-carrageenan
      was good enough to retain biocatalytic activity during prolonged storage at 4
      degrees C.

PMID- 1368013
TI  - Characterization and use of a penicillin acylase biocatalyst.
AB  - A complete characterization of a penicillin acylase biocatalyst is presented,
      including the determination of physicochemical and kinetic parameters. Stability
      studies are detailed in terms of both storage temperature and pH as well as
      operational stability after 150 batch reactions of two hours duration each. An
      Arrhenius-type model was used to simulate the effect of pH on biocatalyst
      stability. A kinetic model is proposed to describe batch and continuous stirred
      tank reactors and to predict the long-term behavior of the process.

PMID- 1368014
TI  - Efficient production of thermostable Thermus thermophilus xylose isomerase in
      Escherichia coli and Bacillus brevis.
AB  - The xylose (glucose) isomerase from the thermophile Thermus thermophilus seems to
      have potential for the development of new isomerization processes using high
      temperatures and slightly acidic pH. The isomerase has an optimum temperature at
      95 degrees C, and is also very stable at high temperatures. The optimum pH is
      around 7.0, close to where by-product formation is minimal. Since Thermus
      produces only a little of this useful isomerase, the production of the cloned
      gene in Escherichia coli and Bacillus brevis were compared. Especially B. brevis
      was able to produce the isomerase efficiently, more than 1 g/l, in spite of the
      high G + C content (67%) of the Thermus gene, and the presence of codons not
      frequently used in E. coli or B. brevis.

PMID- 1368015
TI  - Expression in E. coli of the gene encoding phenylalanine ammonia-lyase from
      Rhodosporidium toruloides.
AB  - The active sites of the enzyme phenylalanine ammonia-lyase (Pal) from
      Rhodosporidium toruloides contains a dehydroalanine residue that is believed to
      be essential for catalytic activity. Furthermore, the dehydroalanine is believed
      to be added post-translationally as part of a prosthetic group covalently
      attached to the enzyme. Perhaps for this reason no attempts to produce Pal in
      foreign host cells have been reported. We have inserted the entire uninterupted
      pal gene from R. toruloides into the Escherichia coli expression vector pKK 223
      3. E. coli cells containing this vector synthesize a protein of the expected
      size, and extracts prepared from these cells contain a Pal-like activity. The
      potential implications of this finding are discussed.

PMID- 1368016
TI  - Extracellular production system of heterologous peptide driven by a secretory
      protease inhibitor of Streptomyces.
AB  - The value of a heterologous peptide extracellular production system in
      Streptomyces using a secretory protease inhibitor, was examined. DNA was
      synthesized encoding apidaecin 1b (AP1), an interesting antibacterial peptide
      discovered in lymph fluid of the honeybee, and was joined to the Streptomyces
      subtilisin inhibitor (SSI) gene via a 12-bp nucleotide sequence corresponding to
      the amino acid sequence specific for cleavage by blood coagulation factor Xa. The
      fusion protein (SSI-AP1) could be expressed and excreted efficiently into the
      medium by culturing S. lividans 66 harbouring a plasmid vector constructed for
      SSI secretion, into which the synthetic DNA was introduced. Sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis and amino acid analysis of the
      purified SSI-AP1 provided reasonable results of molecular size and composition
      value. Interestingly, SSI-AP1 protein showed bifunctional activity: inhibitory
      activity of SSI and antibacterial activity of AP1. The inhibitory activity
      against Escherichia coli could be also detected after the fusion protein was
      cleaved by factor Xa. The extracellular production system presented here should
      provide a useful tool for production, analysis of mode of action, and also for
      genetic improvement of antimicrobial peptides such as apidaecin.

PMID- 1368018
TI  - DNA probes and automation.
AB  - Current methods for DNA probe analysis in principle provide access to the total
      genetic information of any organism and permit applications in health care, for
      example. In practice, however, greatly improved efficiency of methods for
      decoding genetic information is required for both research and routine
      applications. This review describes recent progress towards automated DNA probe
      assays.

PMID- 1368017
TI  - The activity of a model heterologous protein in pep4-3 mutants of Saccharomyces
      cerevisiae.
AB  - The bacterial lacZ gene was introduced into two sibling strains of Saccharomyces
      cerevisiae, one a wild-type strain with normal proteinase activity and the other
      a pep4-3 mutant strain. The pep4-3 mutation resulted in 90% reduced activity of
      the four major vacuolar proteinases. By comparing the activity of the lacZ gene
      product (beta-galactosidase) in both strains the degradative effect of the major
      vacuolar proteinases on a heterologous protein was estimated. The mutant strain
      with reduced proteinase activity had higher beta-galactosidase activity under all
      the test conditions. In the most productive case the pep4-3 mutant had 55% higher
      beta-galactosidase activity than the wild-type. Batch cultures of the two strains
      were evaluated for growth characteristics. The strain with reduced proteinase
      activity grew to higher optical densities than the wild-type. Upon further
      examination it was found that not only were the optical densities of pep4-3
      cultures greater but the cell numbers were much greater than expected due to the
      smaller size of pep4-3 cells. It is concluded that the strain lacking vacuolar
      proteinases maintained increased levels of beta-galactosidase and is
      physiologically as healthy as the wild-type.

PMID- 1368019
TI  - Detection of mutations in DNA.
AB  - Methods for detecting known and unknown mutations are becoming increasingly
      important as new disease genes are identified and new mutations are found in
      them. These methods are also expensive and time consuming. Over the past year
      major efforts have been directed towards developing new assays and making current
      assays faster and cheaper.

PMID- 1368020
TI  - Ribozymes.
AB  - RNA enzymes or ribozymes are receiving considerable attention for their potential
      use as highly specific inhibitors of gene expression. From the basic science
      perspective, the mechanisms by which ribozymes catalyze site-specific cleavage
      (and in some cases ligation) reactions provide exciting and active areas of
      scientific investigation. The most recent developments in our understanding of
      the molecular mechanisms of catalysis, as well as in vivo applications of
      ribozymes, are highlighted.

PMID- 1368021
TI  - Biosensors and flow injection analysis.
AB  - Combining flow injection analysis with a biosensor is a novel biosensing process
      which has allowed speedy and accurate analysis. Diagnostic analysis is the most
      important application for biosensing flow injection analysis, but other
      applications include bioprocess monitoring, analysis of food and agricultural
      products, as well as environmental analysis. In addition, the analysis of
      compounds, such as explosives and abused drugs, and monitoring of Salmonella, the
      microorganism that causes food poisoning, have been reported.

PMID- 1368022
TI  - Fermentation monitoring.
AB  - Fermentation monitoring continues to be the focus of much research. Over the last
      year, important strides were made in improving bioprocess monitoring using NADH
      fluorescence, viscosity, affinity techniques, enzyme and microbial sensors,
      calorimetry, flow injection analysis and bioluminescence. Better fermentation
      monitoring is important for improving understanding, operation, development and
      control of the process. We expect progress in these areas of research to
      continue. In addition, we highlight some non-conventional approaches.

PMID- 1368023
TI  - Carbohydrate analysis.
AB  - The analysis of the carbohydrate chains attached to proteins is becoming
      increasingly important as appreciation of the role of glycosylation in the
      structural and functional properties of biologically significant glycoproteins
      grows. Over the past year, a number of developments have been made that may
      improve and promote the analysis of the glycosylation of proteins.

PMID- 1368024
TI  - Peptide screening.
AB  - Since late 1990, there have been several advances in preparing and screening
      large numbers of various peptides. Developments have continued in methods of
      peptide screening based on peptides exposition on coat proteins, produced via
      fusion coliphage constructs. Further developments have been made in increasing
      the multitude of peptides produced by the chemical synthetic strategy, including
      light-directed, spatially addressable chemical synthesis, single-bead, single
      peptide synthesis, as well as iterative peptide selection and synthesis.

PMID- 1368025
TI  - Capillary electrophoresis.
AB  - The past year has seen major advances in capillary electrophoresis in terms of
      broadening applicability. A variety of successful approaches to peptide/protein
      and DNA separation and analysis are now available, and techniques for saccharide
      analysis are developing rapidly. Capillary electrophoresis--mass spectrometry
      continues to demonstrate its potential as a tool for high-resolution structure
      analysis.

PMID- 1368026
TI  - Analytical biotechnology.

PMID- 1368027
TI  - Application of PCR to human gene detection.
AB  - The advent of the polymerase chain reaction has stimulated the development of a
      number of rapid methods for characterizing human genes. In addition, the
      unprecedented level of sensitivity offered by some of these methods may prove to
      be of great value in the detection of minority cell populations. Over the past
      year, technical developments have been made in this area.

PMID- 1368028
TI  - Biotechnology of Duboisia alkaloids.
AB  - New ways for medicinal plant improvement and for the production of plant drugs
      have opened up as the result of advances in plant biotechnology and increasing
      interest in plant-derived pharmaceuticals. This article highlights plant
      improvement of Duboisia and production of tropane alkaloids using modern
      techniques such as plant tissue and cell culture, root culture, radioimmunoassay
      in tropane alkaloid analysis, and molecular biology in the studies of tropane
      biosynthesis.

PMID- 1368029
TI  - Products liability relating to biotechnology--an overview.

PMID- 1368030
TI  - Eurobarometer measures awareness and attitudes about biotechnology--and who
      people trust to explain it.

PMID- 1368031
TI  - Harvard mouse--eating into the European patent system?

PMID- 1368032
TI  - Extraction and purification of proteins from animal tissue using aqueous phase
      systems.
AB  - Aqueous phase separations offer a novel and different means of extracting and
      purifying proteins from animal tissue at industrial scale. This article gives an
      overview of aqueous phase separations in relation to animal tissue, describes
      some pilot-scale work, and discusses the strengths, weaknesses and future
      prospects for this technology.

PMID- 1368033
TI  - Kaempferol-3-O-glucosyl(1-2)rhamnoside from Ginkgo biloba and a reappraisal of
      other gluco(1-2, 1-3 and 1-4)rhamnoside structures.
AB  - A kaempferol-3-O-glucorhamnoside from Ginkgo biloba is defined as the 3-O-alpha-L
      [ beta-D-glucopyranosyl(1-2)rhamnopyranoside] on the basis of 2D NMR evidence.
      Complete assignments of the 1H and 13C NMR spectra of this compound and of its
      known p-coumaroyl derivative are presented for the first time. The NMR
      distinctions of 1-2, 1-3 and 1-4 linked glucopyranosylrhamnopyranosides are
      discussed and indicate (i) that the 13C NMR assignments for one published gluco(1
      3)rhamnoside are in need of modification, (ii) that the published structure of
      hordenine-O-[6-O-t-cinnamoyl-beta-glucosyl(1-4)-alpha-rhamnoside] from
      Selaginella doederleinii is not distinguished from the 1-3 linked glucorhamnoside
      structure, and (iii) that the 8-prenylkaempferol-3-O-[glucosyl(1-4)rhamnoside]-7
      O-glucoside and the equivalent 4'-O-methylated xylosyl(1-4)rhamnoside from
      Epimedium pubescens and E. washanense, respectively, are (1-2)-linked.

PMID- 1368034
TI  - A bidesmosidic oleanolic acid saponin from Panax pseudo-ginseng.
AB  - A novel triterpenoid saponin, pseudo-ginsenoside-RI3, isolated from the rhizomes
      of Panax pseudo-ginseng subsp. himalaicus var. angustifolius has been
      characterized as 3-O-beta-D-glucopyranosyl(1----2)-beta-D-glucuronopyranosyl (1--
      -6)-beta-D-glucopyranosyl 28-O-beta-D-xylopyranosyl-olean-12-en-28-oic acid ester
      by physicochemical methods.

PMID- 1368035
TI  - Triterpenoid saponins from Clinopodium polycephalum.
AB  - A new triterpenoid saponin, clinopodiside A, has been isolated from Clinopodium
      polycephalum. Its structure was established by spectroscopic methods and X-ray
      diffraction analysis as 3-O-beta-D-glucopyranosyl(1----6)-[ beta-D-glucopyranosyl
      (1----4)]-beta-D-glucopyranosyl-olean-11,13(18)-diene-3 beta,16 beta, 23,28
      tetrol.

PMID- 1368036
TI  - The pregnane glycoside marsdekoiside A from Marsdenia koi.
AB  - A new pregnane glycoside, marsdekoiside A was isolated from the stems of
      Marsdenia koi (Asclepiadaceae) and its structure was elucidated from chemical and
      spectral data as 12-cinnamoyl-dihydrosarcostin-3-O-methyl-6-deoxy-beta-D-allopyr 
      ano syl-(1----4)-O-beta-D-oleandropyranosyl-(1----4)-O-beta-D-++ +cymar
      opyranoside.

PMID- 1368037
TI  - Characterization of proteins released from legume seeds in hot water.
AB  - When immersed in water at 50-60 degrees, mature soybean seeds release a large
      amount of protein. The major protein released was basic 7S globulin (Bg), which
      is present in the cotyledons of soybean seeds. The released Bg consisted of the
      27,000 and 16,000 subunits which were linked by disulphide bonding and
      glycosylated. The released Bg exhibited an identical structure with the mature Bg
      which was synthesized in the normal developing seeds. Proteins like Bg were also
      found to be released into hot water from the seeds of legume species such as
      azuki-bean, cowpea, mung-bean and winged-bean. Besides Bg and Bg-like proteins, a
      few proteins including the 9,000 hydrophobic protein in soybean, ubiquitin in
      cowpea and mung-bean, and Kunitz trypsin inhibitor in winged-bean, were released
      from the seeds in hot water.

PMID- 1368039
TI  - Flavonol glycoside production in callus cultures of Epimedium diphyllum.
AB  - Callus cultures of Epimedium diphyllum produced a large amount of epimedoside A
      in addition to a small amount of diphylloside B, ikarisoside C, epimedoside E,
      diglycosides of des-O-methylanhydroicaritin (8-gamma, gamma
      dimethylallylkaempfero). Icariin, epimedins A-C, which are glycosides of
      anhydroicaritin, were also produced in the callus cultures. Contents of the
      flavonol glycosides in callus tissue were higher than those of mother plants, but
      the composition of each flavonol glycoside mixture in the callus cultures was
      different from that of the original plants. The time-course experiments showed
      that an inverse relationship existed between cell growth and flavonol glycoside
      production. Effects of hormonal factors on cell growth and flavonol glycoside
      production indicated that 2,4-dichlorophenoxyacetic acid was needed for the
      production of flavonol glycosides.

PMID- 1368038
TI  - Biotransformation of isoeugenol and eugenol by cultured cells of Eucalyptus
      perriniana.
AB  - Three new biotransformation products, eugenyl beta-rutinoside, and isoeugenyl
      beta-gentiobioside and beta-rutinoside, together with eugenyl beta-glucoside and
      beta-gentiobioside, and isoeugenyl beta-glucoside, were isolated from jar
      fermentor culture of Eucalyptus perriniana following administration of eugenol
      and isoeugenol, respectively. This is the first report of rhamnosylation in a
      biotransformation catalysed by cultured cells of E. perriniana.

PMID- 1368041
TI  - Vomifoliol 9-O-beta-D-glucopyranosyl-4-O-beta-D-xylopyranosyl-6-O-beta-D-
      glucopyranoside: a trisaccharide glycoside from apple fruit.
AB  - From a methanolic extract of neutralized apple fruit pulp, a minor compound was
      isolated by adsorption chromatography on both XAD and PVPP resins followed by
      rotation locular countercurrent chromatography (RLCC). Clean-up for subsequent
      spectroscopic studies was performed by preparative HPLC on RP-18 and RP-select B
      phases. Data available from UV, NMR and mass spectroscopy together with the
      results obtained by enzymatic and acid hydrolyses revealed the structure of the
      polar glycoside as vomifoliol 9-O-beta-D-glucopyranosyl-4-O-beta-D-xylopyranosyl
      6-O-beta-D-glucopyran oside.

PMID- 1368040
TI  - Caffeic glycoside esters from Jasminum nudiflorum and some related species.
AB  - Poliumoside, forsythoside B, echinacoside and arenarioside, caffeic glycoside
      esters, were isolated from several species of Oleaceae. The
      poliumoside/forsythoside ratio distinguishes Jasminum nudiflorum from J. mesnyi.
      Arenarioside and forsythoside B act in Forsythia species as good hybridization
      markers.

PMID- 1368042
TI  - Withanolide glycosides from Dunalia australis.
AB  - Four new withanolide glycosides, (20R,22R)-O-(3)-[beta-D- xylopyranosyl(1----3),
      beta-D-xylopyranosyl(1----4)]-beta-D-glucopyranosyl-3 beta,20-dihydroxy-1 alpha
      acetoxy-witha-5,24-dienolide, (20R,22R)-O-(3)-[beta-D-xylopyranosyl(1----3), beta
      D-glucopyranosyl(1----4)]-beta-D-glucopyranosyl-3 beta,20-dihydroxy-1 alpha
      acetoxy-witha-5,24-dienolide, (20R,22R)-O-(3)-[beta-D- glucopyranosyl(1----3),
      beta-D-glucopyranosyl(1----4)]-beta-D-glucopyranosyl- 3 beta,20-dihydroxy-1 alpha
      acetoxy-witha-5,24-dienolide and (20R,22R)-O-(3)-[beta-D-glucopyranosyl(1----3),
      beta-D- glucopyranosyl(1----4)]-beta-D-glucopyranosyl-3 beta, 12 beta,20
      trihydroxy- 1 alpha,acetoxy-witha-5,24-dienolide, named dunawithanines C, D, E
      and F, respectively, were isolated from Dunalia australis. Their structures were
      elucidated on the basis of spectral and chemical evidence, especially NMR data of
      the peracetates.

PMID- 1368043
TI  - Structural revision of bryonoside and structure elucidation of minor saponins
      from Bryonia dioica.
AB  - The structure of bryonoside, which has previously been isolated from the roots of
      Bryonia dioica, has been revised. In addition, three new cucurbitacin saponins,
      named brydioside A, B and C have also been obtained. Their structures were
      established on the basis of spectral and chemical evidence.

PMID- 1368044
TI  - On the use of apparent kinetic parameters for immobilized enzyme with
      uncompetitive substrate inhibition [corrected].
AB  - The use of a simple rate equation with apparent parameters to describe the
      kinetic behavior of an immobilized enzyme with uncompetitive [corrected]
      substrate inhibition was assessed. To do so, the reaction rate was calculated as
      a function of the interfacial substrate concentration, and the results were used
      to identify the apparent kinetic parameters by nonlinear regression. This
      procedure was repeated for different values of the diffusional constraints and of
      the inhibition constant. The equation using apparent parameters can describe the
      global kinetic behavior, provided that the diffusional and inhibitory constraints
      are not too high. When the constraints are high, a Michaelis-Menten equation can
      be used to model the kinetics for interfacial concentrations lower than the
      concentration leading to the maximum reaction rate.

PMID- 1368046
TI  - Purification and properties of two pectinesterases from tomatoes.
AB  - Pectinesterase is present in green tomato fruit and increases several-fold during
      ripening. Several isoenzymes of pectinesterase are known to exist in tomatoes,
      but one isoenzyme predominates in the fruit of most cultivars. A few cherry
      tomato cultivars have been identified that contain low levels of this isoenzyme
      and much higher levels of another pectinesterase that is unique to those
      cultivars. The two major pectinesterases were purified to homogeneity and
      characterized. There were significant differences in the pectinesterases but they
      cross-reacted with antibodies raised against them and their N-terminal amino acid
      sequences were similar.

PMID- 1368045
TI  - Comparison of bovine beta-casein hydrolysis by PI and PIII-type proteinases from
      Lactococcus lactis subsp. cremoris [corrected].
AB  - The action of the cell-wall-associated proteinases from Lactococcus lactis subsp.
      cremoris strains H2 and SK112 on bovine beta-casein was compared. The proteinase
      from the H2 strain was characterised as a PI-type proteinase since it did not
      hydrolyse alpha s1-casein and the initial trifluoroacetic acid-soluble products
      of beta-casein hydrolysis were identical to those previously identified as
      hydrolysis products of PI-type lactococcal proteinase action. The time-course of
      product formation by the proteinase from the H2 strain indicated that the bonds
      Tyr193-Gln194 and Gln182-Arg183 were the first to be hydrolysed. Cleavage of the
      bonds Gln175-Lys176, Ser168-Lys169, Ser166-Gln167 and Leu163-Ser164 was also very
      rapid. Four of the five bonds in beta-casein most susceptible to hydrolysis by
      the PIII-type proteinase from strain SK112 were different from those cleaved by
      the PI-type proteinase, initial hydrolysis being at the sites Tyr193-Gln194,
      Leu192-Tyr193, Asp43-Glu44, Gln46-Asp47 and Phe52-Ala53. Early hydrolysis at the
      three sites in the N-terminal region of beta-casein, leading to cleavage of the N
      terminal phosphopeptide and rapid precipitation of the residual fragment,
      represents a marked contrast to the action of PI-type proteinases where cleavage
      at sites in the N-terminal region occurs only very slowly.

PMID- 1368047
TI  - Structural study of cell wall mannan of a Candida albicans (serotype A) strain.
AB  - The structure of the mannan of Candida albicans NIH A-207 strain (serotype A) was
      investigated by adopting mild acetolysis followed by enzymolysis with an
      Arthrobacter GJM-1 exo-alpha-mannosidase. The resultant oligosaccharides, from
      pentaose to octaose (where manp = D-mannopyranose), were identified as manp beta
      (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp, manp beta
      (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)- manp alpha (1--
      -2)manp, manp beta (1----2)manp beta (1----2)manp beta (1----2)manp alpha (1---
      2)manp alpha (1----2)manp alpha (1----2)manp and manp beta (1----2)manp beta (1--
      -2)manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp
      alpha (1----2)manp, respectively. Analyses of alpha-linked oligosaccharides
      obtained by acetolysis under conventional conditions gave the same
      oligosaccharides, from biose to heptaose, as those obtained from the mannans of
      C. albicans NIH B-792 (serotype B) and J-1012 (serotype A, formerly serotype C).

PMID- 1368048
TI  - Partial sequences of 18S ribosomal RNA of two genera from each of six flowering
      plant families.
AB  - Partial nucleotide sequences of 18S ribosomal RNA from two genera of each of six
      families of flowering plants were analysed using parsimony programmes. The
      results are discussed with reference to their usefulness in plant phylogenetic
      studies.

PMID- 1368049
TI  - Triterpenoid saponins from Sophora subprostrata.
AB  - From Sophora subprostrata Radix, the roots of Sophora subprostrata, six
      triterpenoidal saponins having soyasapogenol A, B, sophoradiol and kuzusapogenol
      A as aglycones, were isolated as their methyl esters. The structure of a new
      saponin was established to be 3-O-[alpha-L-rhamnopyranosyl(1----2)-D
      galactopyranosyl(1----2)-beta-D- glucuronopyranosyl] kuzusapogenol A methyl ester
      by means of 1H and 13C NMR spectroscopy and chemical evidence.

PMID- 1368050
TI  - Triterpenoid saponins from Triplostegia grandiflora.
AB  - Four new oleanane triterpenoid saponins named triplosides D-G were isolated from
      the roots of Triplostegia grandiflora. Their structures were elucidated on the
      basis of chemical degradation and spectral evidence. The saponins investigated
      were: oleanolic acid 3-O-beta-D-xylopyranosyl(1----4)-beta-D-xylopyranosyl(1---
      3)-beta-D- xylopyranosyl(1----4)-alpha-L-rhamnopyranosyl(1----3)-beta-D-
      xylopyranosyl(1----3)-alpha-L-rhamnopyranosyl(1----2)-beta-D-xylopyranos ide,
      oleanolic acid 3-O-beta-D-glucopyranosyl(1----6)-[beta-D- xylopyranosyl(1----4)]
      beta-D-glucopyranosyl(1----3)-beta-D- xylopyranosyl(1----4)-alpha-L
      rhamnopyranosyl(1----3)-beta-D- xylopyranosyl(1----3)-alpha-L-rhamnopyranosyl(1--
      -2)-beta-D-xylopyranos ide, oleanolic acid 3-O-beta-D-xylopyranosyl(1----3)-beta
      D-xylopyranosyl(1----4)- alpha-L-rhamnopyranosyl(1----3)-beta-D-xylopyranosyl(1--
      -3)-alpha-L- rhamnopyranosyl(1----2)-beta-D-xylopyranoside and oleanolic acid 3-O
      alpha-L-rhamnopyranosyl(1----3)-beta-D-xylopyranosyl(1---3)-alpha-L-
      rhamnopyranosyl(1----2)-beta-D-xylopyranoside, respectively. All of them have a
      common aglycone and are monodesmosides.

PMID- 1368051
TI  - Steroidal saponins from the rhizomes of Smilax menispermoidea.
AB  - Four steroidal saponins were isolated from the dried rhizomes of Smilax
      menispermoidea. One of them is new and its structure was established as
      (25S)spirost-5-en-3 beta,17 alpha-triol-3-O-[alpha-L-rhamnopyranosyl(1----2)]
      [alhpa-L-rhamnopyranosyl(1----4)]-beta-D-glucopyranoside using spectrometry and
      chemical methods, as well as comparison with three known steroidal saponins,
      dioscin, methyl protodioscin and pseudoprotodioscin.

PMID- 1368052
TI  - Complex flavonol glycosides from the leaves of Ginkgo biloba.

PMID- 1368053
TI  - Triterpenoid saponins from roots of Clematis grata.

PMID- 1368055
TI  - Endogenous gene and amplifiable cDNA construct both produce unstable t-PA mRNA in
      Bowes melanoma cells.
AB  - Bowes melanoma cells, which naturally produce tissue-type plasminogen activator
      (t-PA), were transfected with a plasmid containing a human t-PA cDNA under
      transcriptional control of the promoter/enhancer of the major immediate early
      gene of human cytomegalovirus (CMV) plus genes expressing geneticin (G418)
      resistance and dihydrofolate reductase (DHFR). In one of the initial geneticin
      resistant transformants, t-PA mRNA transcribed from the chromosomally integrated
      plasmid had the same short half-life, 20-30 min, as did mRNA transcribed from the
      endogenous t-PA gene compared to 7-8 h for total poly(A)+ mRNA. After subsequent
      selection of such cells with methotrexate, a cell line was obtained in which the
      t-PA cDNA construct was co-amplified with the DHFR gene and which produced 10
      times more t-PA protein than the original Bowes melanoma cells.

PMID- 1368056
TI  - Tac promoter vectors incorporating the bacteriophage T7 gene 10 translational
      enhancer sequence for improved expression of cloned genes in Escherichia coli.
AB  - Two new plasmid expression vectors, pTacT7 and pTacT7L, have been constructed,
      which incorporate between the tac promoter and a downstream NcoI-HindIII
      polylinker sequence a synthetic sequence derived from the region upstream from
      gene 10 of bacteriophage T7 (g10-L). This sequence was recently shown to act as a
      translational enhancer (Olins et al., 1988) and was termed "Epsilon" (Enhancer of
      Protein Synthesis Initiation) element (Olins and Rangwala, 1989). In this
      communication we describe in detail the construction of ptacT7 and ptacT7L.
      Furthermore, we present evidence that the "Epsilon" element is able to enhance 3
      to 20-fold the expression levels of two poorly expressed test genes encoding the
      human placental proteins PP9 and PP15. On the other hand, the expression levels
      of two highly expressed test genes encoding the human placental proteins PP4 and
      FXIIIa could not be further enhanced by the presence of the "Epsilon" element.
      These experiments show that the T7 gene 10 leader sequence can be utilized to
      improve the expression yields of otherwise poorly expressed heterologous genes in
      Escherichia coli.

PMID- 1368057
TI  - Characterization of glutamine metabolism in two related murine hybridomas.
AB  - Aspects of glutamine metabolism were examined in two related hybridomas, a high
      producing line (PQX B1/2) and a low-producing line (PQX B2/2). The growth and
      metabolic characteristics of both cell lines were identical or very similar.
      During batch growth glutamine was completely exhausted from the medium and an
      examination of the fate of [14C]glutamine highlighted the importance of this
      amino acid as an energy source. The relative enzyme activities and the amount of
      ammonia produced during growth indicated that glutamine is oxidized
      preferentially via the transamination pathway. The overall rate of glutamine
      utilization from the growth medium was similar to the rate of [14C]glutamine
      uptake which suggests that transport may regulate glutamine metabolism.

PMID- 1368058
TI  - The enzymatic synthesis of antiviral agents.
AB  - The majority of potential antiviral agents which are currently undergoing
      clinical trials are inhibitors of the replication of nucleic acids. The most
      common class of these inhibitors are nucleoside analogues and the elucidation of
      synthetic routes to these compounds has been of interest for many years as many
      are anticancer agents. One synthetic development has been the application of bio
      transformations to nucleoside syntheses. This topic has been reviewed recently
      (Shirae et al., 1991) but this review is not widely available. In the present
      review, the application of biotechnology to the synthesis of antiviral agents
      including those which are not nucleoside analogues will be discussed. Enzymatic
      syntheses of nucleosides can be simpler and quicker than syntheses carried out by
      chemical methods. The most useful enzymes are those found in catabolic pathways.
      Nucleoside phosphorylases and N-deoxyribosyltransferases have both been widely
      used for nucleoside synthesis catalysing the transfer of sugar residues from a
      donor nucleoside to a heterocyclic base. Enzymatic methods have also been applied
      to the resolution of racemic mixtures and adenosine deaminase is a convenient
      catalyst for the hydrolysis of amino groups on purines and purine analogues.
      Regioselective deprotection of nucleoside esters has been achieved with lipases
      and these enzymes have also been applied to the synthesis of esters of sugar-like
      alkaloids. The latter have potential as inhibitors of the replication of HIV.
      Esterases have also been used in combined chemical and enzymatic syntheses of
      organophosphorus antiviral agents.

PMID- 1368054
TI  - Clusters of genes for the biosynthesis of antibiotics: regulatory genes and
      overproduction of pharmaceuticals.
AB  - In the last decade numerous genes involved in the biosynthesis of antibiotics,
      pigments, herbicides and other secondary metabolites have been cloned. The genes
      involved in the biosynthesis of penicillin, cephalosporin and cephamycins are
      organized in clusters as occurs also with the biosynthetic genes of other
      antibiotics and secondary metabolites (see review by Martin and Liras [65]). We
      have cloned genes involved in the biosynthesis of beta-lactam antibiotics from
      five different beta-lactam producing organisms both eucaryotic (Penicillium
      chrysogenum, Cephalosporium acremonium (syn. Acremonium chrysogenum) Aspergillus
      nidulans) and procaryotic (Nocardia lactamdurans, Streptomyces clavuligerus). In
      P. chrysogenum and A. nidulans the organization of the pcbAB, pcbC and penDE
      genes for ACV synthetase, IPN synthase and IPN acyltransferase showed a similar
      arrangement. In A. chrysogenum two different clusters of genes have been cloned.
      The cluster of early genes encodes ACV synthetase and IPN synthase, whereas the
      cluster of late genes encodes deacetoxycephalosporin C synthetase/hydroxylase and
      deacetylcephalosporin C acetyltransferase. In N. lactamdurans and S. clavuligerus
      a cluster of early cephamycin genes has been fully characterized. It includes the
      lat (for lysine-6-aminotransferase), pcbAB (for ACV synthase) and pcbC (for IPN
      synthase) genes. Pathway-specific regulatory genes which act in a positive (or
      negative) form are associated with clusters of genes involved in antibiotic
      biosynthesis. In addition, widely acting positive regulatory elements exert a
      pleiotropic control on secondary metabolism and differentiation of antibiotic
      producing microorganisms. The application of recombinant DNA techniques will
      contribute significantly to the improvement of fermentation organisms.

PMID- 1368059
TI  - Structural characteristics of an abnormal protein influencing its proteolytic
      susceptibility.
AB  - Structural properties of two similar beta-galactosidase fragments were
      investigated to determine how they influence the fragments' degradation rate in
      Escherichia coli. Both fragments resulting from a C-terminal nonsense mutation in
      lacZ, the CSH11 polypeptide and its 90 kDa degradative intermediate, exist
      predominantly as monomer subunits instead of in the tetrameric form
      characteristic of the native enzyme. However, both fragments appear to produce
      trace amounts of dimers and tetramers. The tetramer and higher molecular weight
      aggregates formed by the wild-type subunit confer greater protection for the
      enzyme's N-terminal auto-alpha polypeptide than does the monomer state of the
      beta-galactosidase fragments. The thermally induced aggregation of both beta
      galactosidase fragments correlates with their sensitivity to alpha-chymotrypsin.
      The relatively low thermal stability of the 90 kDa degradative intermediate
      appears to be the cause of the significant increase in its proteolytic
      susceptibility at moderately high temperatures.

PMID- 1368060
TI  - Secretion of correctly processed and folded pancreatic secretory trypsin
      inhibitor by Bacillus subtilis.
AB  - We constructed a plasmid, designated pNPP126, containing a DNA sequence encoding
      a fusion protein composed of Bacillus amyloliquefaciens neutral protease
      prepeptide (signal peptide) and human pancreatic secretory trypsin inhibitor
      (hPSTI), where the mature hPSTI is accurately fused to the 3'-terminal of the
      prepeptide coding region. It was observed that the strain Bacillus subtilis MT600
      harboring pNPP126 could secrete a trypsin inhibitory activity into the culture
      medium. The N-terminal amino acid sequence, the amino acid composition and the
      stoichiometry of the purified hPSTI produced by B. subtilis were the same as
      those of natural hPSTI, indicating that the transformant B. subtilis MT600
      (pNPP126) could efficiently secrete the correctly processed and folded hPSTI into
      the culture medium.

PMID- 1368061
TI  - On the safety of Aspergillus oryzae: a review.

PMID- 1368062
TI  - Controlled mycelial growth for kojic acid production using Ca-alginate
      immobilized fungal cells.
AB  - Conidia of Aspergillus oryzae were immobilized in Ca-alginate beads and then
      incubated in a nutrient medium to yield an immobilized biocatalyst producing
      kojic acid. The immobilized cell cultures produced kojic acid linearly during
      cultivation. Regardless of the size of the immobilized particles, there existed
      an optimal nitrogen concentration for the maximum production rate of kojic acid,
      at which smaller bead sizes resulted in a higher production rate. When the growth
      of mycelia were confined within the bead surface and segregated from each other
      by gel material, they produced kojic acid with maximal catalytic activity and
      exhibited the highest conversion yield of glucose. The extent of mycelial
      segregation was especially higher in cultures of smaller bead particles, and the
      depth of mycelial growth was 150 to 250 microns from the gel bead surface in all
      cultures of different nitrogen concentrations and bead sizes. Therefore, for the
      maximum expression of catalytic activities of immobilized mycelial cultures, it
      was found very critical to optimally control the mycelial distribution in gel
      beads by the culture conditions affecting mycelial growth.

PMID- 1368063
TI  - Production of androsta-1,4-diene-3,17-dione from cholesterol using immobilized
      growing cells of Mycobacterium sp. NRRL B-3683 adsorbed on solid carriers.
AB  - Living cells of Mycobacterium sp. NRRL B-3683 were immobilized by adsorption on
      different types of solid carriers in order to produce androsta-1,4-diene-3,17
      dione (ADD) from cholesterol. Activated alumina proved to be the most preferred
      carrier for long-term operation when glucose and peptone were added to the
      reaction medium. In a repeated-batch process, the maximum productivity of ADD was
      about 0.19 g/l per day with a molar conversion rate of 77% when 1.0 g/l of
      cholesterol was added to the reaction medium. The half-life of the immobilized
      cells was more than 45 days and the system could be reactivated by incubating the
      immobilized cells in a cell growth medium.

PMID- 1368064
TI  - Microbial modification of sugars as building blocks for chemicals.
AB  - Investigations on the microbial modification of sucrose to the corresponding 3
      keto-derivative were carried out with resting cells of Agrobacterium tumefaciens
      NCPPB 396. This highly specific oxidation to yield the 3-keto-derivative has been
      analysed kinetically with varying substrate and cell mass concentrations. The
      formation of the corresponding 3-keto-derivative depended strongly on the
      reaction time and the aeration rate and was maximal at aeration rates up to 11.5
      volume air/cultivation volume per minute with resting cells. The product
      formation increased with increasing substrate concentrations. However, the
      product yield was maximal at substrate concentrations below 20 g/l. Data
      pertaining to the production of active cell mass as well as for maximal 3-keto
      derivative formation are presented in this paper. Also included are some
      applications for these derivatives.

PMID- 1368065
TI  - Growth characteristics of Sanguinaria canadensis L. cell suspensions and
      immobilized cultures for production of benzophenanthridine alkaloids.
AB  - Sanguinaria canadensis L. plants were harvested from a local forest and calli
      were initiated from leaf explants. The production of benzophenanthridine
      alkaloids (i.e. sanguinarine, sanguilutine, sanguirubine, chelerythrine,
      chelilutine and chelirubine) by S. canadensis cell grown in modified B5 and IM2
      media was compared to the alkaloid content of rhizomes. Sanguinarine accounted
      for approximately 80% of the total alkaloid content of cultured cells (1.3%, g g
      1) while sanguinarine and sanguirubine accounted for 70% of rhizome alkaloids
      (9.0%, g g-1). Sanguinarine, chelirubine and chelerythrine were the only known
      alkaloids detected in cultured S. canadensis cells. Maximum alkaloid production
      of cultures performed using B5 medium, containing half the original nitrate
      concentration, was observed following extracellular nitrate and sugar depletion.
      The scale-up of this culture was successfully performed in a 2-1 immobilization
      bioreactor. The consumption of sugar and nitrate as well as the oxygen (OTR) and
      carbon dioxide (CTR) transfer rates of the immobilized cell culture were
      monitored for 15 days. The maximum sugar and nitrate consumption rates were 1.8 g
      l-1 per day and 2.3 mM per day respectively. The maximum OTR and CTR of the
      immobilized cell culture were 0.8 mmol O2 l-1 h-1 and 0.95 mmol CO2 l-1 h-1
      respectively. The sanguinarine yield of this culture reached 1.0% based on
      biomass dry weight (g g-1 dw) by day 15.

PMID- 1368066
TI  - Extra- and intracellular metabolite concentrations for murine hybridoma cells.
AB  - Intra- and extracellular metabolite concentrations were determined for hybridoma
      cells grown in tissue culture flasks in batch culture. Significant differences
      were found for intracellular lactate and amino acid concentrations depending on
      the culture medium. AB2-143.2 cells cultivated in Dulbecco's modified Eagle's
      (DME) medium supplemented with 50 mM lactate exhibited intracellular lactate and
      glutamine levels of 40 mM and 4 mM, respectively, whereas cells grown in standard
      DME medium had low intracellular glutamine and 20 mM lactate concentrations. For
      cells cultivated in medium supplemented with 6 mM pyruvate, intracellular lactate
      levels were estimated at approx. 40 mM, but these cells also showed an increased
      intracellular alanine concentration of 22 mM. The higher alanine pools probably
      result from increased transamination of pyruvate under these conditions.

PMID- 1368067
TI  - High expression vectors for the production of recombinant single-chain urinary
      plasminogen activator from Escherichia coli.
AB  - An expression cassette containing a synonymous gene for human single-chain
      urokinase-type plasminogen activator (Rscu-PA) 5'-flanked by a trp promoter and
      the Shine-Dalgarno sequence of the xyl A operon of Bacillus subtilis and
      terminated by the terminators trp A and Tn10 was constructed and inserted into a
      pBR322 derivative to yield pBF160. When compared to pUK54 trp 207-1 containing
      the natural scu-PA gene without the Shine-Dalgarno sequence and terminator, the
      expression efficiency of pBF160 in Escherichia coli strains was improved by one
      order of magnitude. Replacement of the trp by the tac promoter (pBF171) did not
      affect expression. Inserting the Shine-Dalgarno sequence and Tn10 terminator into
      pUK54 trp 207-1 (pWH1320) slightly increased the expression level, whereas
      elimination of the Shine-Dalgarno sequence and the terminators from pBF160 with
      almost complete conservation of the synonymous structural gene (pBF191)
      significantly reduced the expression. Variation of the distance between the Shine
      Dalgarno sequence and the start codon between 8 and 10 bp (pBF163) proved
      irrelevant. In conclusion, poor expression of mammalian genes in E. coli may
      result from both improperly designed regulatory elements and structural features
      of the coding region and therefore de-novo synthesis of the gene may be required
      to obtain satisfactory expression.

PMID- 1368068
TI  - Targeted integrative transformation of Candida tropicalis by electroporation.
AB  - A method for integrative transformation of the diploid yeast Candida tropicalis
      by electroporation has been developed. by linearizing the transforming plasmid
      DNA containing the URA3 gene prior to electroporation of recipient cells, its
      integration was targeted to a specific locus in the genome, resulting in single
      or multiple tandem integrations. The optimal electroporation conditions for this
      yeast were established and include an electric pulse of 2.25 kV/cm for a duration
      of 50 ms. Using these conditions, Ura+ transformants were readily obtained at a
      high frequency (45 transformants/micrograms DNA) as the result of targeted
      integration of the URA3 gene containing plasmid DNA at the chromosomal ura3
      locus. The number of transformants resulting from this procedure is comparable to
      that achieved with a recently reported spheroplast transformation procedure for
      C. tropicalis; in addition, it offers the advantages of being simple, rapid and
      reproducible.

PMID- 1368069
TI  - Enhanced expression of heterologous proteins by the use of a superinducible
      vector in budding yeast.
AB  - We report the effects of a strong overexpression of the GAL4 activator protein on
      the expression of UASGAL regulated genes, obtained by cloning the GAL4 gene and
      the GAL1-10 upstream activating sequence (UASGAL)-lacZ fusion in the same high
      copy number plasmid. Comparable amounts of active enzyme were obtained by host
      strains usually producing different levels of cloned proteins due to their
      different genetic background. The transformed cells constitutively produced low
      levels of beta-galactosidase (1-2% of total proteins) both in glucose and in
      raffinose minimal media. Nevertheless, expression was still inducible and a
      tenfold induction could be rapidly obtained by the addition of 0.5% (w/v)
      galactose to the culture, even when glucose was still present in the medium.

PMID- 1368070
TI  - Changing glycine 21 for glutamic acid in the beta-subunit of penicillin G acylase
      from Kluyvera citrophila prevents protein maturation.
AB  - Active penicillin acylase from Kluyvera citrophila strain ATCC 21,285 consists of
      two different alpha- and beta-subunits derived from a single precursor by post
      translational processing. Using the chemical mutagen hydroxylamine we have
      treated plasmid pYKD59 containing the active penicillin acylase gene (pga) from
      K. citrophila and have generated different point mutant penicillin acylase genes,
      one producing a maturation deficient precursor. This point mutation has changed
      the glycine 310 residue of the precursor for a glutamic acid (residue number 21
      of the mature beta-subunit). The introduction of a charged residue in this
      position did not prevent translocation of the precursor to the periplasm but the
      resultant molecule was not able to undergo subsequent post-translational
      modification to yield the active protein.

PMID- 1368071
TI  - Adsorption of polycyclic aromatic hydrocarbons (PAHs) by soil particles:
      influence on biodegradability and biotoxicity.
AB  - Polycyclic aromatic hydrocarbon (PAH) biodegradation was investigated in
      contaminated soils from two different industrial sites under simulated land
      treatment conditions. Soil samples from a former impregnation plant (soil A)
      showed high degradation rates of PAHs by the autochthonous microorganisms,
      whereas PAHs in material of a closed-down coking plant (soil B) were not degraded
      even after inoculation with bacteria known to effectively degrade PAHs. As rapid
      PAH biodegradation in soil B was observed after PAHs were extracted and restored
      into the extracted soil material, the kind of PAH binding in soil B appears to
      completely prevent biodegradation. Sorption of PAHs onto extracted material of
      soil B follows a two-phase process (fast and slow); the latter is discussed in
      terms of migration of PAHs into soil organic matter, representing less accessible
      sites within the soil matrix. Such sorbed PAHs are suggested to be non
      bioavailable and thus non-biodegradable. By eluting soil B with water, no
      biotoxicity, assayed as inhibition of bioluminescence, was detected in the
      aqueous phase. When treating soil A analogously, a distinct toxicity was
      observed, which was reduced relative to the amount of activated carbon added to
      the soil material. The data suggest that sorption of organic pollutants onto soil
      organic matter significantly affects biodegradability as well as biotoxicity.

PMID- 1368072
TI  - Immobilized metal ion affinity chromatography of serum albumins.
AB  - The interaction of several serum albumins with chelated (iminodiacetate, IDA) and
      immobilized (agarose-IDA) metal ions, Co2+, Ni2+, Cu2+ and Zn2+, was studied.
      There was no retention of human, bovine, porcine, murine and avian albumins on
      IDA-Zn(II) and IDA-Co(II) columns. However, all albumins studied, i.e., those of:
      man, cow, pig, dog, rabbit, rat, mouse, chicken and pigeon were retained on IDA
      Cu(II) columns, and all except dog albumin were retained also on IDA-Ni(II). The
      recognition of albumins by chelated and immobilized transition metals seems to be
      related to an affinity for the imidazole side chains. It is postulated that one
      to three imidazoles is involved in this interaction, under the employed
      experimental conditions (pH 7.0; 1 M sodium chloride). There is no evidence for
      any significant contribution of tryptophan or cysteine (Cys 34) residues to the
      chromatographic event. The retention of defatted albumin and albumin oligomers
      (human), on IDA-Cu(II) columns was not significantly different from that of non
      defatted albumin or albumin monomer, respectively.

PMID- 1368074
TI  - Application of aqueous two-phase partition in PEG-phosphate systems. Design and
      implementation of a prototype process for recovery of bulk protein fractions from
      waste brewer's yeast.
AB  - The practical development of a process exploiting aqueous two-phase partition in
      PEG/phosphate systems is described for the recovery and partial purification of a
      bulk protein fraction from waste Brewer's yeast. Inadequacies in current
      assumptions concerning de novo process design of such systems necessitated the
      empirical establishment of conditions for the two-step extraction of protein from
      wet-milled yeast suspensions. Experiments with homogeneous proteins and yeast
      extracts are presented to illustrate the true influence of phase volume upon
      primary protein extraction, and of added salts and modified system pH upon
      selective back extraction. A mechanistic description of physical and chemical
      factors influential upon selective phase partition in PEG/phosphate systems is
      discussed.

PMID- 1368073
TI  - A model for the prediction of partition coefficients in aqueous two-phase
      systems.
AB  - A mathematical model has been developed to predict partition coefficients for
      aqueous two-phase systems. The model is based on a previously-developed equation
      for partitioning which arises from an osmotic pressure viral expansion. The model
      suggests that the properties of importance are the concentration difference of
      one of the phase-forming components, such as a polymer, and the hydrophobicity of
      the solute relative to the hydrophobic-hydrophilic difference between the two
      phases. Several two-phase systems have been studied, with a particular emphasis
      on the poly(ethylene glycol)/magnesium sulfate system. Numerous solutes,
      including peptides, were used in this system and their partition coefficients
      show good agreement with the model.

PMID- 1368075
TI  - Recovery of biocatalysis products from reversed micellar reaction media: a
      preliminary evaluation of membrane extractors.
AB  - It has been demonstrated that ultrafiltration membranes of sufficiently low
      molecular weight cutoff can be used to retain reversed micelles and their hosted
      enzymes, while permitting the recovery of lipophilic products of enzymatically
      catalysed, synthesis reactions in a stripping solution on the other side of the
      membrane. Calculations indicate that hollow fibre membranes having the same
      rejection characteristics and solvent resistance as the flat sheet membranes,
      will provide an attractive and efficient means for the recovery of these
      biosynthesis products; currently, such membrane modules are not available
      commercially.

PMID- 1368076
TI  - Temperature dependence of the partition coefficient of proteins in aqueous two
      phase systems.
AB  - We report the partition coefficients of lysozyme, chymotrypsinogen-A, albumin and
      catalase in sixty four Polyethyleneglycol/Dextran/Water systems at 4, 25 and 40
      degrees C. We found that the partition coefficients of the four proteins
      generally increase with increasing temperature. The influence of temperature on
      the partition coefficient seems to be highly dependent on the kind of protein
      which is partitioned and on the total polymer concentration, but does not, in
      general, depend on the molecular weight of the polymers. The partition
      coefficients of small and hydrophilic proteins like lysozyme and chymotrypsinogen
      A are only slightly affected by changes in temperature, while the partition
      coefficients of bigger and more hydrophobic proteins like albumin and catalase
      are strongly affected by changes in temperature. The results suggest the
      incorporation of attractive forces (possible electrostatic) into a model
      previously reported by us.

PMID- 1368077
TI  - Liquid fluidized bed adsorption of protein in the presence of cells.
AB  - The adsorption, in a liquid fluidized bed, of Bovine Serum Albumin (BSA), onto an
      ion-exchange absorbent, Q-Sepharose Fast Flow, in the presence of Alcaligenes
      eutrophus cells, has been studied. The expansion of the fluidized bed is greater
      in the presence than in the absence of cells and obeys the laws of Richardson and
      Zaki. The effect of cell concentration on the equilibrium adsorption
      characteristics of the adsorbent has been assessed. The rate of adsorption of BSA
      onto the adsorbent has been studied in a batch stirred tank, and a fluidized bed
      system both in the presence and absence of cells. Comparisons have been made with
      the adsorption of human immunoglobulin G (human IgG), onto an affinity adsorbent,
      Protein A Sepharose CL-4B. The data from the fluidized bed breakthrough tests
      have been used to assess the validity of a theoretical model adapted from one
      that predicts the performance of the adsorption phase in the absence of cells in
      fixed bed systems. Tests have been done on the washing phase in the fluidized bed
      adsorption system to establish the most efficient method of washing cells and
      unadsorbed protein out of the bed.

PMID- 1368078
TI  - Optimization and scale up of the adsorption fractionation of cod pyloric caeca
      deoxyribonuclease using axial and radial flow columns.
AB  - The key step in the purification of a deoxyribonuclease (DNase) from extracts of
      cod (Gadus morhua L.) pyloric caeca, is the selective retention of the enzyme by
      anion exchange chromatography. The cod DNase purification on Q-Sepharose Fast
      Flow (Pharmacia) was optimized, using a 60 ml fixed-bed column. In combination
      with titration curve analysis, we have screened the effect of buffer pHs, feed
      conductivity and protein loading, on the product recovery and purity. We have
      developed elution conditions which allow effective separation of the cod DNase
      from bounded impurities, such as proteinases and nucleic acids. Low levels of
      these impurities were regarded as essential for the desired product quality. The
      optimum resolution and maximum purification (ca. 20-fold increase in specific
      activity) of DNase, was, however, achieved at low protein loading (2.6 mg ml-1
      gel), corresponding to less than 4% of the dynamic bed capacity. Scale-up to a
      2.5 l pilot scale column (axial flow) and a 0.25 l radial flow column showed that
      the separation and yield obtained at laboratory scale was retained, and was
      independent of column geometry and bed height. The implications for a production
      scale scenario of 100 g of fractionated protein, are also discussed, as well as
      process hygiene. The optimization described herein adds further knowledge to the
      treatment of fish waste and the downstream processing of valuable biochemicals
      from marine raw material.

PMID- 1368079
TI  - Combined chemical and mechanical processes for the disruption of bacteria.
AB  - Mechanical cell disruption by high pressure homogenisation or high speed bead
      mills is currently the general method of choice for the large scale disruption of
      micro-organisms; however, deleterious effects include the high energy
      requirement, the need for efficient cooling to prevent the excessive heating of
      the product and the micronisation of cell debris. Certain chemical treatments for
      microbial cell disruption alter the permeability of bacteria and yeasts, allowing
      partial release of soluble products. Such treatments are insufficient for the
      recovery of granular intracellular products. As cell wall strength has been cited
      as a major factor influencing the requirements for efficient mechanical
      disruption, the use of chemical pretreatment to decrease cell wall strength prior
      to mechanical breakage by homogenisation has been considered. The following
      treatments were shown to increase the sensitivity of the Gram-negative bacterium,
      Alcaligenes eutrophus, to disruption: alkaline pH shock, the addition of an
      anionic detergent, increase of the monovalent cation concentration, the addition
      of EDTA and enzymic lysis by lysozyme. These pretreatments allow equivalent
      disruption to be achieved at lower operating pressures or fewer passes through
      the homogeniser. Alkaline pH pretreatment at pH 10.5 allowed a 37.5% increase in
      soluble protein release on subsequent homogenisation. An increase of some 30% in
      soluble protein release was found following prior addition of 0.137 M monovalent
      cations (Na+ or K+) at 60 degrees C. Treatment with an anionic detergent showed a
      considerable decrease in the number of passes required through the homogeniser.
      Maximum cell rupture can thus be accomplished at reduced energy inputs.

PMID- 1368080
TI  - The use of dyes in protein purification.
AB  - The role of the matrix, ligand and linking mechanism in affinity chromatography
      is discussed, special emphasis being placed on the use of dyestuff molecules as
      ligands. Current knowledge of dye-protein interactions is outlined and problems
      arising from the use of conventional textile dyes as ligands are considered. Work
      on the synthesis of novel dye-like molecules designed specifically for affinity
      chromatography is reviewed. This is seen as leading to the development of
      improved affinity systems capable of advancing the utility of affinity
      chromatography in protein purification.

PMID- 1368081
TI  - Production and purification of L-phenylalanine oxidase from Morganella morganii.
AB  - An enzyme fraction, acting predominantly on L-phenylalanine has been purified and
      characterized from Morganella morganii. The total envelope was prepared by
      disrupting the cells with a French press followed by high speed centrifugation.
      After solubilization of the particulate fraction with 0.1% Triton X-100 and then
      centrifugation, the resulting supernatant was layered onto a DEAE-Cellulose
      column. Active fractions eluted were applied to a Phenyl-Sepharose CL-4B column
      as the final purification step. The activity of the purified enzyme to various L
      amino acids in decreasing order was phenylalanine, methionine, leucine,
      tryptophan, and to a much lesser extent cysteine and tyrosine. At 4 degrees C in
      20 mM phosphate buffer pH 7.5, the partially purified fractions collected from
      the DEAE-Cellulose column were stable for 120 h. On the other hand, the purified
      fractions obtained from the Phenyl Sepharose CL-4B column showed a drastic
      decrease in activity within only 24 h. Mg2+ (up to 40 mM), Mn2+ or Ca2+ (up to 10
      mM) stimulated the oxidation of the purified enzyme but increases beyond such
      levels decreased the enzyme activity. Co2+ (0.05 mM), Cu2+ (0.5 mM) or Zn2+ (0.1
      mM) decreased the enzyme activity 37, 33 and 20%, respectively.

PMID- 1368082
TI  - The disruption of Alcaligenes eutrophus by high pressure homogenisation: key
      factors involved in the process.
AB  - The disruption of the Gram-negative bacterium Alcaligenes eutrophus by high
      pressure homogenisation, using the APV Gaulin 15M 8BA and 30CD homogenisers is
      reported. The operating parameters such as operating pressure, number of passes,
      temperature and biomass concentration, mimicked trends previously reported for
      yeasts. Extension of the study to consider the effect of cell characteristics,
      including the growth rate, size and shape, illustrated the dominant effect of the
      growth phase. The improved disruption of bacterial cultures in the logarithmic
      phase with respect to stationary phase cultures was confirmed by an increased
      dependence of actively growing cultures on the operating pressure. An increase in
      size in excess of 30% on the accumulation of the storage product, PHB in the
      stationary phase caused little change in the ease of disruption. The use of
      transmission electron microscopy to directly monitor the disruption on multiple
      passes shed light on the two-stage nature of this disruption process.

PMID- 1368083
TI  - Large scale production of human albumin: three years experience of an affinity
      chromatography process.
AB  - Immobilized Cibacron Blue is a well-known tool for the separation of a number of
      proteins and enzymes. Among them, human plasma albumin was easily purified from
      crude plasma and consequently, this approach represents an interesting way for a
      production scale. Our data describes about three years of experience in the
      production of human albumin using large columns of immobilized Cibacron Blue. The
      amount of albumin produced per cycle was about 250 g on a column of about 50 l.
      Over 500 cycles the final purity of albumin was very high and constant (98-100%).
      The albumin yield of the chromatographic fractionation was approximately 82%. The
      column performance remained acceptable when regeneration operations were applied
      to the sorbent. The long life of the sorbent renders this approach very
      attractive and economically acceptable for large scale applications.

PMID- 1368084
TI  - The interaction of the factor VIII/von Willebrand factor complex (VIII/vWf), with
      guanidinium-derivatized matrices.
AB  - Five different guanidinium (Gu)-derivatized agarose matrices were investigated
      for their potential in chromatographically resolving the Factor VIII/von
      Willebrand complex, VIII/vWf, fibrinogen, Fg, and fibronectin, Fn, from
      cryoprecipitate. Using conventional NaCl gradient methodology it was found that
      the order of elution of specific plasma proteins, and the yield of VIII/vWf,
      varied with the methods used to derivatize the agarose beads. Good yields of
      VIII:C (generally 30-45%) were obtained with Gu-matrices prepared by bis-oxirane
      coupling procedures. Cryoprecipitate binding studies showed that the capacity of
      Gu-Sepharose 4B, prepared by isourea modification of amino-Sepharose 4B, was 36
      units VIII/vWf per ml matrix. The product, depleted of both Fg and Fn, had a
      specific activity of 2 units VIII:C per mg total protein, (yield 100% vWf:Ag and
      47% VIII:C).

PMID- 1368086
TI  - Oligonucleotide analysis by anion exchange HPLC.
AB  - The ability to resolve and purify synthetic oligonucleotides by high performance
      anion exchange chromatography was evaluated using two wide pore polymeric HPLC
      matrices. The materials used are rigid macroporous copolymers which have a fully
      quaternised polyethyleneimine coating to provide a strong anion exchange,
      quaternary amine, functionality. Oligomers of poly(rA), poly(rC) and RNA produced
      by alkaline hydrolysis of the polymers were chromatographed to evaluate the
      selectivity of the system prior to the analysis of synthetic oligonucleotides
      produced using a commercial oligonucleotide synthesizer.

PMID- 1368085
TI  - An aqueous hydroxypropylstarch-poly(ethylene glycol) two-phase system for
      extraction of alpha-lactalbumin and beta-lactoglobulin from bovine whey.
AB  - The partitioning of alpha-lactalbumin and beta-lactoglobulin from bovine whey has
      been studied in an aqueous poly(ethylene glycol) (PEG)-hydroxypropylstarch two
      phase system. The influence of several parameters including concentrations of
      polymers, sodium phosphate buffer, KSCN, and of PEG palmitate, with and without
      the presence of Ca2+, on the partitioning of the proteins has been investigated.
      The separation of the two proteins was demonstrated by counter-current
      distribution. A purification procedure for both proteins has been developed by
      using PEG-hydroxypropylstarch two-phase system. This system is compared with the
      more costly standard system based on PEG and dextran. The possible use of the
      aqueous two-phase systems for batch extraction for large scale purification of
      these whey proteins is discussed.

PMID- 1368087
TI  - The effects of magnetic stabilization on the structure and performance of liquid
      fluidized beds.
AB  - Liquid fluidized beds containing porous magnetic ion-exchange particles with
      densities ca. 1.03-1.16 g mL-1 were examined. The effect of magnetic
      stabilization was studied, both in terms of bed physical characteristics and
      sorptive behavior. Maximum applied magnetic field strength was approximately 200
      oersted. Breakthrough and pulse analyses were carried out with protein and
      acetone solutions, respectively, with liquid flow rates ranging from
      approximately 1 to 3 cm min-1. Acetone pulses in columns containing 7 mL of
      particles had plate numbers ranging from 2.5 to 18 for magnetically stabilized
      beds and from 7.8 to 20 for non-stabilized fluidized beds. Under any particular
      set of conditions, magnetic stabilization always resulted in poorer efficiency,
      both in pulse analyses and in protein breakthrough experiments.

PMID- 1368088
TI  - A kinetic analysis of cell disruption by bead mill. The influence of bead
      loading, bead size and agitator speed.
AB  - The influence of operating parameters such as bead loading, peripheral velocity
      and bead size on the kinetic behavior of cell disruption in a bead mill was
      investigated. The bead mill was equipped with a single rotating disc and operated
      batchwise. Analysis of the data showed that the frequency of bead collision may
      be correlated to the observed first-order process, applying a new concept called
      effective disruption volume. It was found that the first-order rate constant was
      proportional to the square of bead loading within the other experimental
      conditions examined and increased with the decrease in bead diameter. A new
      disruption kinetics was proposed, explaining all the observed data in terms of
      the frequency of bead collision and the concept of effective disruption volume.
      Although other types of microorganisms were not examined, the concept may well be
      extended to various kinds of cells.

PMID- 1368089
TI  - Enzyme purification using temperature-induced phase formation.
AB  - A new type of aqueous two-phase system composed of an ethylene oxide and
      propylene oxide random co-polymer, UCON 50-HB-5100, as the upper phase polymer
      and either dextran or hydroxypropyl starch as the lower phase polymer has been
      characterized and used to purify 3-phosphoglycerate kinase (EC 2.7.2.3) and
      hexokinase (EC 2.7.1.1) from bakers' yeast. The UCON 50-HB-5100 polymer has a
      cloud point of 55 degrees C at which temperature it phase separates from water.
      This cloud point can be lowered to 40 degrees C by the addition of 0.2 M sodium
      sulfate salt. The low cloud point of this UCON polymer makes it possible to
      obtain the target enzymes in a water and buffer solution, and to recover and
      recycle the UCON 50-HB-5100 polymer. The phase diagrams for the systems UCON 50
      HB-5100/Dextran T500 and UCON 50-HB-5100/hydroxypropyl starch have been
      determined. Yeast homogenate was first partitioned in a system composed of a top
      phase containing UCON 50-HB-5100 and a bottom phase containing either dextran or
      hydroxypropyl starch. The top phase containing the enzyme free of cell debris was
      removed and the temperature increased above the cloud point of the UCON until a
      new two phase system composed of water as the top phase and a concentrated liquid
      UCON 50-HB-5100 bottom phase was formed. The water phase containing the enzyme
      was removed and the bottom phase containing the UCON 50-HB-5100 could be recycled
      to perform a second extraction.

PMID- 1368090
TI  - A simple solution to positive cell isolation.

PMID- 1368091
TI  - A cost-effective approach to gel documentation and image analysis.

PMID- 1368092
TI  - An improved three-dimensional visualization method for confocal microscopy.

PMID- 1368093
TI  - Aching for approval, hoping for harmony--biotech product regulation.

PMID- 1368094
TI  - What's 'new' in patent law?

PMID- 1368095
TI  - Antibody engineering--how to be human.

PMID- 1368096
TI  - Glycoprotein pharmaceuticals: scientific and regulatory considerations, and the
      US Orphan Drug Act.

PMID- 1368097
TI  - Recombinant inbred mouse strains: models for disease study.
AB  - Recombinant inbred (RI) strains of mice and the closely related recombinant
      congenic strains offer considerable promise for identifying and characterizing
      genes causally associated with many different diseases. Loci associated with
      diseases such as heart disease, autoimmune disease and leukemia have already been
      identified through the use of these unique strains.

PMID- 1368098
TI  - Responsive polymer systems for controlled delivery of therapeutics.
AB  - The ideal drug-delivery system should provide therapeutics in response to
      physiological requirements, having the capacity to 'sense' changes and alter the
      drug-release process accordingly. Such responsive controlled delivery systems are
      still at an experimental stage. This review focuses on two basic approaches: (1)
      externally regulated systems (utilizing triggers such as magnetism, ultrasound,
      temperature and electricity), and (2) self-regulated systems (utilizing pH
      sensitive polymers, enzyme-substrate reactions, competitive binding, and antibody
      interactions).

PMID- 1368099
TI  - Septic shock. What do physicians want?

PMID- 1368100
TI  - Transformation of microbes, plants and animals by particle bombardment.
AB  - Over the past several years, particle bombardment has evolved into a useful tool
      for molecular biologists, allowing direct gene transfer to a broad range of cell
      and tissue types. Some of the important applications of the process include the
      production of transgenic crop species including maize and soybean and the
      introduction of DNA into plastids and mitochondria. Recent results have extended
      the range of gene transfer by particle bombardment to animal and bacterial cells.
      One noteworthy newer application is the direct insertion of genes into the organs
      of living animals. Here we discuss these advances and the instrument developments
      that contributed to them.

PMID- 1368101
TI  - Production of active Bacillus licheniformis alpha-amylase in tobacco and its
      application in starch liquefaction.
AB  - As a first example of the feasibility of producing industrial bulk enzymes in
      plants, we have expressed Bacillus licheniformis alpha-amylase in transgenic
      tobacco, and applied the seeds directly in starch liquification. The enzyme was
      properly secreted into the intercellular space, and maximum expression levels of
      about 0.3% of total soluble protein were obtained. No apparent effect of the
      presence of the enzyme on plant phenotype was observed. The molecular weight of
      the enzyme produced in tobacco was around 64 kD. The difference, compared to 55.2
      kD for the bacterial enzyme, was found to result from complex-type carbohydrate
      chains attached to the protein. Application studies on the liquefaction of starch
      were done with transgenic seeds containing the recombinant alpha-amylase. The
      resulting hydrolysis products were virtually identical with those obtained from
      degradation with alpha-amylase from Bacillus licheniformis.

PMID- 1368102
TI  - Optimizing nucleotide mixtures to encode specific subsets of amino acids for semi
      random mutagenesis.
AB  - In random mutagenesis, synthesis of an NNN triplet (i.e. equiprobable A, C, G,
      and T at each of the three positions in the codon) could be considered an optimal
      nucleotide mixture because all 20 amino acids are encoded. NN(G,C) might be
      considered a slightly more intelligent "dope" because the entire set of amino
      acids is still encoded using only half as many codons. Using a general algorithm
      described herein, it is possible to formulate more complex doping schemes which
      encode specific subsets of the twenty amino acids, excluding others from the mix.
      Maximizing the equiprobability of amino acid residues contributing to such a
      subset is suggested as an optimal basis for performing semi-random mutagenesis.
      This is important for reducing the nucleotide complexity of combinatorial
      cassettes so that "sequence space" can be searched more efficiently. Computer
      programs have been developed to provide tables of optimized dopes compatible with
      automated DNA synthesizers.

PMID- 1368103
TI  - Production and biological activity of hybrid growth hormone-releasing hormone
      propeptides.
AB  - Growth hormone-releasing hormone (GHRH), a hypothalamic hormone that stimulates
      the synthesis and release of growth hormone (GH) from anterior pituitary cells,
      has been previously produced by synthetic peptide chemistry and recombinant DNA
      procedures. GHRH is capable of stimulating growth as well as eliciting other
      anabolic effects on animals and thus may have potential applications in
      agriculture and human medicine. However, economical production of GHRH by
      recombinant DNA process has been difficult since GHRH is degraded rapidly by
      endogenous E. coli proteases. We report here an efficient process to produce
      hybrid GHRH analogs of higher molecular weight. These hybrid GHRH propeptides
      (proGHRH) are comprised of an analog of GHRH (44 aa) and the human GHRH carboxy
      terminal peptide (33 aa). In E. coli K-12 RV308, the expression levels of the
      proGHRH analogs were estimated to be 10% of the total cellular protein. An in
      vitro assay to measure the release of rat growth hormone by GHRH analogs using
      crude E. coli lysates was also developed. This assay showed that the proGHRH
      analogs produced in E. coli efficiently stimulated GH release from rat anterior
      pituitary cells. One proGHRH analog, [alao]-proGHRH, was purified ans shown to
      efficiently elevate plasma GH levels in wether lambs. Our data indicate that the
      hybrid proGHRH peptides, unlike other hormone propeptides such as proinsulin, are
      remarkably bioactive.

PMID- 1368104
TI  - Production of cytotoxic proteins in Escherichia coli: a fermentation process for
      producing enzymatically active HIV-1 protease.
AB  - Two fermentation processes for the tryptophan-regulated expression of active HIV
      protease (HIV-1 prt) in Escherichia coli are described. Since overexpression of
      HIV-1 prt results in cell death, stringent control of product expression was
      necessary to attain high enzyme levels. Such control was achieved by separation
      of growth and production phases in a two-step process or by implementation of
      nutrient feed in a one-step process. When the two-stage process was used, soluble
      product was detectable only when induction occurred at low culture density (A550
      less than 3.5). Short induction periods of 1-2 h and rapid harvesting were
      necessary to recover active product. Similar results were obtained when the
      single-stage process was operated at 37 degrees C; however, cultivation and
      induction at 28 degrees C resulted in active enzyme formation following induction
      at increased cell density (A550 = 10).

PMID- 1368105
TI  - Growth and the production of penicillins in Penicillium chrysogenum with palm oil
      and its various fractions as carbon sources.
AB  - The utilisation of palm oil and its fractions by Penicillium chrysogenum for
      growth and penicillin production is strain-dependent. Strain H1107 could utilise
      crude palm oil, its liquid (palm olein) and solid (palm stearin) fractions and
      its component fatty acids (oleic, palmitic, stearic and myristic) as the main
      carbon source; strain M223 could not. Cell-bound lipase activity was higher in
      H1107 than in M223.

PMID- 1368106
TI  - Monitoring and control of biotechnological production processes by Bio-FET-FIA
      sensors.
AB  - Single and multisensor field effect transistors (FET) with a pH-sensitive
      Si/SiO2/Si3N4/Ta2O5-gate and reference electrode (for single sensor) were
      developed and used for manufacturing the following biological (Bio)-FETs: for
      glucose analysis, glucose oxidase-FET (GOD-FET); for urea analysis, urease-FET;
      and for cephalosporin C analysis, cephalosporinase-FET. The GOD-FETs were
      integrated into flow injection analysis (FIA) of the Eppendorf variables analyser
      (EVA) system and used for monitoring the glucose concentration in microbial
      cultivation and production processes with recombinant Escherichia coli K12 MF,
      recombinant E. coli JM103, Saccharomyces cerevisiae H620, and Candida boidinii.
      Urease-FET-FIA was used to monitor the urea concentration in a simulated
      cultivation of Cephalosporium acremonium and urease-FET-FIA and GOD-FET-FIA for
      the monitoring of urea and glucose concentrations in simulated S. cerevisiae
      cultivations.

PMID- 1368107
TI  - Cell-wall-associated proteinase of Lactobacillus delbrueckii subsp. bulgaricus
      CNRZ 397: differential extraction, purification and properties of the enzyme.
AB  - Whole cells of Lactobacillus delbrueckii subsp. bulgaricus CNRZ 397 were able to
      hydrolyse alpha- and beta-caseins. Irrespective of the growth medium used, milk
      or De Man-Rogosa-Sharpe (MRS) broth, identical patterns of alpha- and beta-casein
      hydrolytic products, respectively, were visualized by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. A soluble proteinase present in cell-wall
      extracts was active on caseins and displayed the same hydrolytic patterns as
      whole cells. It was purified from cell-wall extract to homogeneity by
      ultrafiltration and ion exchange chromatography. The enzyme is a monomer with a
      molecular mass of 170 kDa, an optimum temperature of 42 degrees C and an optimum
      pH of 5.5. It was strongly activated by dithiothreitol and partially inhibited by
      E-64. These properties indicate that cysteine residues play an important role in
      the enzyme mechanism. The purified proteinase was not able to hydrolyse di- or
      tripeptides.

PMID- 1368108
TI  - N-terminal amino acid sequence of Brevibacterium sp. R312 wide-spectrum amidase.
AB  - A wide-spectrum amidase from Brevibacterium sp. R312 was partially purified. The
      enzyme subunit was purified by reversed phase HPLC and the N-terminal amino acid
      sequence was found to be identical to that of Pseudomonas aeruginosa aliphatic
      amidase.

PMID- 1368109
TI  - A novel micromanipulation technique for measuring the bursting strength of single
      mammalian cells.
AB  - Information about the bursting strength of animal cells is essential if the
      mechanisms of cell damage in bioreactors are to be understood, and if cell
      mechanical properties are ever to be related to cell structure and physiology. We
      have developed a novel cell compression technique that makes it possible to
      directly measure the bursting strength of single mammalian cells, and to infer
      information about cell mechanical properties.

PMID- 1368110
TI  - In-vivo processing of the initiator methionine from recombinant methionyl human
      interleukin-6 synthesized in Escherichia coli overproducing aminopeptidase-P.
AB  - Human interleukin 6 (hIL-6) overproduced in Escherichia coli HB101 was found to
      partially retain the initiator methionine (Met) residue (Met-hIL-6). In order to
      remove the residual N-terminal Met in vivo, an attempt was made to express hIL-6
      in aminopeptidase-P (Ap-P)-hyperproducing strains, since the N-terminus Met-Pro-
      structure of nascent recombinant hIL-6 has been shown to be a favoured substrate
      of the enzyme in vitro. Using a mutant with duplicated Ap-P genes (pepP) on a
      chromosome or some recombinant strains overproducing Ap-P, we have succeeded in
      removing the initiator Met from Met-hIL-6 in vivo. The content of the mature
      product without the initiator Met in the pepP recombinant strains could be
      increased to approximately 99% from 85%.

PMID- 1368112
TI  - Degradation of 3-chloro-2-methylpropionic acid by Xanthobacter sp. CIMW 99.
AB  - Both stereoisomers of 3-chloro-2-methylpropionic acid (CMPA) and its methyl
      esters (MeCMPA) serve as growth substrates for a bacterial isolate (Xanthobacter
      sp. CIMW 99) when supplied as sole source of carbon and energy. Biodegradation of
      DL-CMPA and DL-MeCMPA was shown to be via a common pathway; an initial,
      constitutive, esterase converted the methyl ester to the corresponding carboxylic
      acid. Further metabolism required the activation of CMPA involving a CoA-, ATP-,
      Mg(2+)-dependent chloroacyl-CoA synthetase. Most noteworthy, it was the product
      of this reaction (3-chloro-2-methylpropionyl-CoA) that underwent hydrolytic
      dehalogenation to give 3-hydroxy-2-methylpropionyl-CoA (3-hydroxyisobutyryl-CoA).
      Further biodegradation proceeded by the action of a dehydrogenase on the CoA
      derivative to give methylmalonate-CoA-semialdehyde. Cells of CIMW 99 also
      contained a stable, constitutive, highly active 3-hydroxyisobutyrate
      dehydrogenase that was specific for the L(+) isomer. However, evidence is
      presented suggesting that this enzyme was not involved in the catabolism of the
      chlorinated substrates.

PMID- 1368111
TI  - Degradation and mineralization of 3-chlorobiphenyl by a mixed aerobic bacterial
      culture.
AB  - A mixed bacterial culture obtained from polychlorinated-biphenyl-contaminated
      river sediments proved capable of degrading 3-chlorobiphenyl (3-CB) under aerobic
      laboratory conditions. Almost total mineralization of 150 mg/l of 3-CB occurred
      when, after 3 days of incubation, the mineral medium was supplied with benzoic
      acid as a carbon source. Two strains of Pseudomonas capable of degrading the
      substrate to 3-chlorobenzoic acid and a strain of Pseudomonas fluorescens capable
      of co-metabolizing this metabolite were selected from the mixed culture. A nearly
      stoichiometric amount of chloride, which defines the percentage of total
      mineralization, was eliminated during mixed culture growth.

PMID- 1368113
TI  - Silicone-immobilized biocatalysts effective for bioconversions in nonaqueous
      media.
AB  - A hydrophobic silicone polymer could be effectively applied to immobilization of
      two kinds of biocatalysts operating in organic media. Horse liver alcohol
      dehydrogenase, which was solubilized in a small amount of water, or deposited on
      water-filled hydrophilic particles, was immobilized in this material. This
      configuration of the preparation involving finely dispersed aqueous phase
      permitted a simple packed-bed operation for the enzymatic oxidation of alcohol
      and reduction of aldehyde with a coupled-substrate NAD(H) recycling in n-hexane.
      Another example was the immobilization of Nocardia corallina which catalysed
      epoxidation of liquid alkenes such as 1-tetradecene, 1-octene, and styrene in the
      presence of n-hexadecane. In order to adjust the hydrophobicity-hydrophilicity
      balance of the support, it was effective to immobilize the cells in a mixed
      matrix composed of silicone polymer and Ca-alginate gel. The optimum composition
      of the mixed matrix, which yielded the highest productivity of epoxide, was 80
      90% silicone + 20-10% alginate for the production of 1,2-epoxytetradecane, 40-50%
      silicone + 60-50% alginate for 1,2-epoxyoctane, and almost 0% silicone + 100%
      alginate for styrene oxide. This significant change of the optimum composition
      was primarily associated with the degree of substrate inhibition.

PMID- 1368114
TI  - Production and immobilization of D-aminoacylase of Alcaligenes faecalis DA1 for
      optical resolution of N-acyl-DL-amino acids.
AB  - The production of D-aminoacylase by Alcaligenes faecalis DA1 was induced 5- to 50
      fold by N-acetyl-D-amino acids. This strain produced about 443 units of D
      aminoacylase and 52 units of L-aminoacylase per gram of cells (wet weight) when
      cultivated in a medium containing 1% N-acetyl-DL-leucine as the carbon source.
      The D-aminoacylase was partially purified by Fractogel DEAE 650 column
      chromatography and then immobilized on another Fractogel DEAE 650 column. The
      catalytic activity of the immobilized D-aminoacylase was 2,650 units per
      milliliter of gel. The Km values for the free and the immobilized enzymes were
      found to be 1.00 and 0.22 mM, respectively, using N-acetyl-D-methionine as a
      substrate. The optimal reaction pH and temperature for both soluble and
      immobilized enzyme were around 8.0 and 45 degrees C, respectively. The free
      enzyme was stable in the pH range from 5.0 to 11.0, whereas the immobilized
      enzyme tended to detach from the gel at pH values higher than 9.0. Both forms of
      enzyme were stable up to 40 degrees C. When used for the optical resolution of N
      acetyl-DL-methionine, the immobilized enzyme maintained 90% initial activity
      after 17 days of continuous operation at 45 degrees C. The process of
      purification and immobilization of D-aminoacylase described in this report is
      very effective and easy to scale up.

PMID- 1368115
TI  - Determination of glucose and ethanol effective diffusion coefficients in Ca
      alginate gel.
AB  - Glucose and ethanol diffusion coefficients in 2% Ca-alginate gel were measured
      using the experimental technique based on solute diffusion into or out of gel
      beads in a well-stirred solution. The aim of the study was to make the
      measurements under typical conditions found in alcoholic fermentations, such as
      the concentrations of glucose (100 g l-1) and ethanol (50 g l-1), the
      simultaneous counter-diffusion of glucose and ethanol, and the presence of cells
      in the gel beads at a level of 10(9) cells g-1 of beads. Previously, an
      evaluation of the error associated with the methodology used indicated how the
      experimental procedure would minimize the error. The individual measurement of
      glucose and ethanol coefficients in 2% Ca-alginate with no cells gave values of
      5.1 and 9.6 x 10(-6) cm2 s-1, respectively, which are lower than those in water.
      When the effect of counter-diffusion was investigated, both coefficients
      decreased: glucose by 14% and ethanol by 28%. When cells were incorporated into
      the beads, only the ethanol coefficient decreased significantly, while the
      glucose coefficient apparently increased its value to 6.9 10(-6) cm2 s-1.

PMID- 1368117
TI  - IL-1-induced procoagulant and fibrinolytic activities of human endothelium grown
      on carbodiimide crosslinked proteins.
AB  - We examined the regulation of procoagulant activity and the production of
      fibrinolytic components by human vascular endothelium grown on coating membranes
      of gelatin, pure or mixed with albumin, crosslinked by carbodiimide ((G)C, (AG)C)
      in comparison with plastic culture dishes. Confluent monolayers were stimulated
      by human recombinant interleukin (IL-1 beta) and responses in terms of tissue
      factors like procoagulant activity, tissue plasminogen activator (tPA) and
      plasminogen activator inhibitor (PAI-1) were followed for up to 72 h.
      Procoagulant activity of cell extracts displayed similar patterns whatever the
      substratum tested. Quantitative immunological assays revealed a 2-fold increase
      in tPA antigen released from monolayers grown on (G)C and on (AG)C compared to
      cells grown on plastic. Exposure of monolayers to IL-1 beta reduced the secretion
      of tPA antigen which still reached higher values on coated than on uncoated
      substratum. We found that the quasi-totality of tPA formed stable complexes with
      PAI-1, thereby suppressing measurable fibrinolytic activity. IL-1 beta stimulated
      the release of PAI-1 antigen quantified by immunoassay and the kinetics of
      secretion were comparable on both coated and uncoated substratum.

PMID- 1368118
TI  - Production of recombinant protein C in serum-containing and serum-free perfusion
      culture.
AB  - For the development of a perfusion culture producing recombinant human protein C,
      the effects of fetal calf serum and growth factors on cell growth and recombinant
      protein production were investigated. Although the growth of recombinant cells
      was stimulated by serum in a dose-dependent manner, a lower concentration of
      serum (2%) could support both synthesis and post-translational modification of
      protein C as efficiently as 10% serum. Among the growth factors tested,
      transferrin enhanced protein C production to the level comparable with 10% serum,
      while insulin was effective in maintaining cellular metabolism. Based on these
      results, a perfusion culture for a scale-up production of recombinant protein C
      was done using an Opticell culture system. A good productivity of the recombinant
      protein was obtained in low serum or serum-free medium for more than one month.

PMID- 1368116
TI  - Explant organ culture: a review.
AB  - Organ explant culture models offer several significant advantages for studies of
      patho-physiologic mechanisms like cell injury, secretion, differentiation and
      structure development. Organs or small explants/slices can be removed in vivo and
      maintained in vitro for extended periods of time if careful attention is paid to
      the media composition, substrate selection, and atmosphere. In the case of human
      tissues obtained from autopsy or surgery, additional attention must be paid to
      the postmortem interval, temperature, hydration, and cause of death. Explant
      organ culture has been effectively utilized to establish outgrowth cell cultures
      and characterize the histiotypic relationships between the various cell types
      within an organ or tissue.

PMID- 1368120
TI  - Cell cycle, cell size and mitochondrial activity of hybridoma cells during batch
      cultivation.
AB  - Cell cycle, cell size and rhodamine 123 fluorescence in cell populations of two
      batch cultures were analysed and quantified with a fluorescence-activated cell
      sorter (FACS). Two cultures derived from either exponential or stationary phase
      innocula were investigated in order to demonstrate the dependency of the
      subsequent cell growth on innoculum condition. The results demonstrated that the
      level of activity of cells in the innoculum culture could have a significant
      effect on cellular activity during the initial phase of the inoculated culture,
      as it advances through its growth cycle. Positive correlation was found between
      the cell size and mitochondrial activity (as measured by rhodamine 123 uptake)
      with S and G2 fractions as the cell progressed through the cell cycle. The
      enumeration of the fractions of cell cycle phases has helped in prediction of the
      changes in cell numbers following perturbation of the culture condition.

PMID- 1368119
TI  - A novel Vero cell line for use as a mammalian host-vector system in serum-free
      medium.
AB  - We have established a novel cell line from a Vero cell derivative that is useful
      for expression of exogenous genes and protein production. Parental Vero-317 cells
      can grow in biotin-containing Eagle's MEM without supplements. By transforming
      this cell line with replication origin-defective SV40 DNA, which contains a
      temperature-sensitive tsA58 large T antigen gene, we established the Verots S3
      cell line that amplified a SV40-origin containing plasmid. The cell line
      expressed a human growth hormone (hGH) gene insert with higher efficiency than
      COS-7 cells in 5% serum-containing MEM and could grow and continue hGH expression
      in protein-free MEM. However, temperature-sensitive shut down of hGH production
      was observed not immediately but 3 days after the temperature shift from 33
      degrees C to 39.5 degrees C.

PMID- 1368121
TI  - Expression of fibronectin and laminin by different types of mouse glial cells
      cultured in a serum-free medium.
AB  - The expression of fibronectin and laminin by cultured glial cells was studied.
      The glial culture from neonatal mouse cerebra maintained in a chemically defined,
      serum-free medium consisted of type-1 astrocytes, oligodendrocyte-type-2
      astrocyte (O-2A) progenitor cells, oligodendrocytes and type-2 astrocytes. Double
      labelling immunofluorescent experiments performed using the mixed glial culture
      indicated that fibronectin and laminin are expressed in different patterns among
      the glial subtypes. The staining intensities with anti-fibronectin or anti
      laminin antibodies decreased in the order: type-1 astrocytes, O-2A progenitor
      cells and type-2 astrocytes. Both molecules were deposited in a fibrillar matrix
      underneath type-1 astrocytes, whereas only intracytoplasmic localization of these
      molecules was observed with O-2A progenitor cells and type-2 astrocytes. Western
      blot analysis showed that glial fibronectin has a slightly higher molecular
      weight than mouse plasma fibronectin (230 kDa) and that glial laminin is a
      variant with a 220 kDa B chain present and the 400 kDa A chain missing. Using
      enzyme-linked immunosorbent assays (ELISA), these molecules were detected in the
      glial extracellular matrix at the concentration of 4 ng/10(6) cells. A large
      amount of fibronectin (82 ng/10(6) cells) was secreted into the culture medium,
      while secretion of laminin was not detected.

PMID- 1368122
TI  - Insecticidal activity and processing in larval gut juices of genetically
      engineered 130-kDa proteins of Bacillus thuringiensis subsp. aizawai.
AB  - The 130-kDa insecticidal protein (IP) of Bacillus thuringiensis subsp. aizawai is
      proteolytically processed in the gut juice of susceptible insect larvae to yield
      an insecticidally active 60-kDa fragment. Twenty-seven mutant IP genes with the
      replacement of codons for Arg and Lys with codons for Gln in the active fragment
      and its adjacent regions of the 130-kDa IP were constructed by site-directed
      mutagenesis and expressed in Escherichia coli cells. The produced mutant IPs at
      Arg87, Arg131, Arg198, Arg311, Arg368, Arg402, Arg458, Arg502, Arg512, Arg524,
      Arg526, Arg528, and Arg601 had reduced insecticidal activity against Spodoptera
      litura larvae. The mutant at Arg601 was sensitive to proteolytic digestion in the
      gut juice of S. litura larvae. Although the mutants at Arg619, Lys622, and Lys637
      had nearly the same activity as that of the wild type, the mutant with the triple
      replacement at Arg619, Lys622, and Lys637 was 2.5 times more active against S.
      litura larvae than the wild type. This triple mutant showed a slightly different
      processing profile in the gut juice than that of the wild type.

PMID- 1368123
TI  - Synthesis of four peptide derivatives to build the sequence corresponding to 31
      53 of human epidermal growth factor (h-EGF).

PMID- 1368124
TI  - C-terminal identification of AD74, a proteolytic product of Enterococcus faecalis
      aggregation substance: application of liquid chromatography/mass spectrometry.
AB  - Sexual aggregation involved in conjugative transfer of Enterococcus faecalis
      plasmid pAD1 is enhanced by the sex pheromone cAD1, which is excreted from
      recipient cells. A membrane-anchored 137 kDa protein is a pAD1-encoded
      aggregation substance designated asal, which is responsible for cell-cell contact
      and leads to the aggregation of cells. An AD74 protein is a proteolytic product
      corresponding to the N-terminal half of asal. The C-terminal of AD74 was
      identified as lysine at position 510 (K-510) by liquid chromatography/mass
      spectrometry (LC/MS): it indicates that asal is cleaved specifically between K
      510 and G-511.

PMID- 1368125
TI  - Purification and refolding of recombinant human IGF II from silkworms infected
      with recombinant Bombyx mori nuclear polyhedrosis virus.
AB  - We have reported that insulin-like growth factor II (IGF II) was produced as a
      fusion protein in Bombyx mori (silkworm) larval bodies infected with recombinant
      B. mori nuclear polyhedrosis virus [J. Gen. Virol., 68, 2599-2606 (1987)]. In
      this study, the purification of IGF II from the infected silkworms is reported.
      The fusion protein was extracted with 6.0 M guanidine-HCl from the infected
      larval bodies homogenized in water. The use of organic solvents to remove the
      impurities, such as lipid derived from the larval bodies, was a very effective
      method of purification. IGF II was released from the partially purified fusion
      protein by treatment with CNBr, purified by HPLC, and refolded by air
      oxidization. Refolded IGF II had an identical primary structure including
      disulfide bonds and showed identical thymidine uptake stimulation activity with
      human IGF II. Furthermore, protein disulfide-isomerase was shown to be able to
      refold scrambled IGF II rapidly.

PMID- 1368126
TI  - Mitochondrial DNA of Marchantia polymorpha as a single circular form with no
      incorporation of foreign DNA.
AB  - A cosmid library and physical maps of mitochondrial DNA (mtDNA) from a liverwort,
      Marchantia polymorpha, were constructed using the cosmid clones. Electrophoresis
      profile and the physical maps indicated that the liverwort mtDNA was
      approximately 183 kb long, the smallest among plant mtDNAs, and that it consisted
      of a single circular molecule. Southern hybridization analysis showed that genes
      typical to the mitochondrial genome existed in a single copy, and also that there
      was no incorporation of chloroplast DNA fragments into the mitochondrial genome.

PMID- 1368127
TI  - Isolation and structural elucidation of the major genuine soybean saponin.

PMID- 1368128
TI  - Priming effects of vegetable juice on endogenous production of tumor necrosis
      factor.

PMID- 1368129
TI  - Induction of neutrophil accumulation by vegetable juice.

PMID- 1368130
TI  - Inhibition by perilla juice of tumor necrosis factor production.

PMID- 1368131
TI  - Characterization of mouse alpha-amylase secreted from Saccharomyces cerevisiae by
      the pGKL 128 kDa killer secretion signal.

PMID- 1368132
TI  - Cross-activity between pheromone biosynthesis activating neuropeptide (PBAN) and
      myotropic pyrokinin insect peptides.

PMID- 1368133
TI  - Isolation, characterization, and antitumor activities of the cell wall
      polysaccharides from Elsinoe leucospila.
AB  - A cell-wall preparation from the cells of Elsinoe leucospila, which produces
      elsinan extracellularly when grown on sucrose or glucose-potato extract medium,
      was fractionated systematically. The heteropolysaccharide that was released by
      treatment with Actinase E digestion, comprised D-mannose, D-galactose, and D
      glucose (molar ratio, 1.5:1.0:0.1). Methylation, mild acid hydrolysis, and 13C
      NMR studies suggested that the polysaccharide contains a backbone of alpha-(1---
      6)-linked D-mannose residues having two kinds of side chains, one attached at the
      O-4 with single or short beta-(1----6)-linked D-galactofuranosyl residues, and
      the other attached at O-2 with short side chains, most probably, of alpha-(1---
      3)-linked D-mannopyranosyl residues. A moderately branched D-glucan fraction,
      obtained from the cold alkali extract, was fractionated to give an antitumor
      active purified beta-(1----3)-glucan having branches of single beta-D-glucosyl
      groups, one out of eight D-glucose residues being substituted at the O-6.

PMID- 1368134
TI  - pH-dependent flagella formation by facultative alkaliphilic Bacillus sp. C-125.
AB  - A facultative alkaliphilic strain of Bacillus sp. C-125 grown at alkaline pH had
      many sinuous peritrichous flagella and was highly motile. However, most of the
      cells grown initially at pH 7 were non-motile and possessed few straight
      flagella. The amount of flagellin was low when the organism was grown at pH 7,
      suggesting that non-motility is due to poor synthesis of flagellin. The molecular
      mass of the flagellin was 37 kDa and the isoelectric point was pH 5.0. The amino
      acid composition of the flagellin was similar to that found in the flagellin from
      neutrophilic Bacillus subtilis 168.

PMID- 1368135
TI  - The carboxyl-terminal half-molecule of ovotransferrin prepared by selective
      digestion of the amino-terminal lobe with thermolysin.
AB  - Diferric ovotransferrin was hydrolyzed by thermolysin, a thermostable protease,
      at elevated temperatures. At 65 degrees C, the amino(N)-terminal lobe was
      completely digested into small peptides, while the carboxyl(C)-terminal lobe was
      significantly resistant to the protease. This permitted the isolation of an iron
      bound C-terminal half-molecule consisting of a glycosylated single polypeptide in
      an excellent yield (about 90%). The fragment comprises the residues from 336 to
      the C-terminus of ovotransferrin. The results for the visible absorption spectrum
      of the copper-bound fragment, the stability of the iron-bound fragment in high
      concentration of urea, and the CD spectra of the fragment in the far and near UV
      regions indicated that it retains the metal binding activity and conformation of
      the C-terminal lobe of intact ovotransferrin.

PMID- 1368136
TI  - Cloning and nucleotide sequence of the maltopentaose-forming amylase gene from
      Pseudomonas sp. KO-8940.
AB  - The gene coding for the maltopentaose-(G5)-forming amylase of Pseudomonas sp. KO
      8940 was cloned into Escherichia coli and its nucleotides were sequenced. It was
      expected that a long open reading frame composed of 1,842-bp that encoded 614
      amino acid residues for secretory precursor polypeptide including the typical
      signal sequence with an NH2-terminal was the gene. An extract of Escherichia coli
      carrying the cloned G5-forming amylase gene had amylolytic activity with which
      produced only G5 from starch, the same as that of the donor strain enzyme. In the
      deduced primary structure of this enzyme, the four conserved regions of many
      alpha-amylases were found, and the COOH-terminal portion of this enzyme showed
      high homology with other raw starch digesting amylases.

PMID- 1368137
TI  - Purification and characterization of an antibiotic substance produced from
      Rhizopus oligosporus IFO 8631.
AB  - We obtained a purified antibiotic protein from the submerged cultivation broth of
      Rhizopus oligosporus IFO 8631 by using CM-Cellulofine chromatography and HPLC.
      The antibiotic did not show a broad spectrum of activity, but it was very active
      against some of the Bacillus species, especially against Bacillus subtillis (B.
      natto) at a very low concentration (less than 1 ppm). It also showed activity
      against other gram-positive bacteria, including Staphylococcus aureus and
      Streptococcus cremoris. The purified antibiotic was a simple protein of about
      5,500 in molecular weight, the amino acid component being characteristically high
      in cystine content. This high cystine content contributed to the stability of the
      antibiotic over a wide pH range and against strong heating (50% of the activity
      remained after boiling for 1 hr).

PMID- 1368138
TI  - Fermentative degradation of dipicolinic acid (pyridine-2,6-dicarboxylic acid) by
      a defined coculture of strictly anaerobic bacteria.
AB  - Degradation of dipicolinic acid (pyridine-2,6-dicarboxylic acid) under strictly
      anaerobic conditions was studied in enrichment cultures from marine and
      freshwater sediments. In all cases, dipicolinic acid was completely degraded.
      From an enrichment culture from a marine sediment, a defined coculture of two
      bacteria was isolated. The dipicolinic acid-fermenting bacterium was a Gram
      negative, non-sporeforming strictly anaerobic short rod which utilized
      dipicolinic acid as sole source of carbon, energy, and nitrogen, and fermented it
      to acetate, propionate, ammonia, and 2CO2. No other substrate was fermented. This
      bacterium could be cultivated only in coculture with another Gram-negative, non
      sporeforming rod from the same enrichment culture which oxidized acetate to CO2
      with fumarate, malate, or elemental sulfur as electron acceptor, similar to
      Desulfuromonas acetoxidans. Since this metabolic activity is not important in
      substrate degradation by the coculture, the basis of the dependence of the
      dipicolinic acid-degrading bacterium on the sulfur reducer may be sought in the
      assimilatory metabolism.

PMID- 1368139
TI  - Optimization of trichloroethylene oxidation by methanotrophs and the use of a
      colorimetric assay to detect soluble methane monooxygenase activity.
AB  - Methylosinus trichosporium OB3b biosynthesizes a broad specificity soluble
      methane monooxygenase that rapidly oxidizes trichloroethylene (TCE). The
      selective expression of the soluble methane monooxygenase was followed in vivo by
      a rapid colorimetric assay. Naphthalene was oxidized by purified soluble methane
      monooxygenase or by cells grown in copper-deficient media to a mixture of 1
      naphthol and 2-naphthol. The naphthols were detected by reaction with
      tetrazotized o-dianisidine to form purple diazo dyes with large molar
      absorptivities. The rate of color formation with the rapid assay correlated with
      the velocity of TCE oxidation that was determined by gas chromatography. Both
      assays were used to optimize conditions for TCE oxidation by M. trichosporium
      OB3b and to test several methanotrophic bacteria for the ability to oxidize TCE
      and naphthalene.

PMID- 1368140
TI  - Isolation and growth of a bacterium able to degrade nitrilotriacetic acid under
      denitrifying conditions.
AB  - A Gram-negative bacterium was isolated from river sediment which was able to grow
      with nitrilotriacetic acid as a combined carbon, nitrogen and energy source in
      the absence of molecular oxygen using nitrate as the terminal electron acceptor.
      Batch growth parameters and mass balances are reported for growth under both
      aerobic and denitrifying conditions. The strain was characterized with respect to
      its substrate spectrum and other physiological properties. This denitrifying
      isolate is serologically unrelated to the comprehensively described Gram-negative
      obligately aerobic NTA-degrading bacteria all of which belong to the alpha
      subclass of Proteobacteria. Chemotaxonomic characterization, which revealed the
      presence of spermidine as the main polyamine and ubiquinone Q-8, excludes the new
      isolate from the phylogenetically redefined genus Pseudomonas and indicates a
      possible location within the gamma-subclass of Proteobacteria close to, but
      separate from the genus Xanthomonas.

PMID- 1368141
TI  - Phosphonate utilization by bacteria in the presence of alternative phosphorus
      sources.
AB  - Batch and continuous culture experiments were carried out to investigate the
      effect of orthophosphate and p-nitrophenylphosphate on the utilization of various
      phosphonates as a P source by bacteria. Detailed tests with methylphosphonate as
      a model phosphonate and the phosphonate-degrading Pseudomonas paucimobilis strain
      MMM101a revealed that, in contrast with the majority of literature data, the
      phosphates did not suppress phosphonate utilization. Under conditions of P
      stress, strain MMM101a simultaneously took up both P-sources, with a preference
      for the phosphate-P. Study of the kinetic parameters for strain MMM101a, growing
      on the different P sources revealed similar, rather low, maximum growth rates
      (ca. 0.15 h-1). However, the affinity for orthophosphate (Ks:0.17 microM), was
      more than two orders of magnitude higher than for methylphosphonate (Ks: 66
      microM), which might account for the preferential uptake of orthophosphate.
      Cellular phosphorus yields in continuous cultures varied considerably with the
      conditions applied. The results suggest that phosphonate degradation can occur
      also in environments with substantial backgrounds of phosphate.

PMID- 1368142
TI  - Initial steps in the degradation of benzene sulfonic acid, 4-toluene sulfonic
      acids, and orthanilic acid in Alcaligenes sp. strain O-1.
AB  - Alcaligenes sp. strain O-1 grew with benzene sulfonate (BS) as sole carbon source
      for growth with either NH4+ or NH4+ plus orthanilate (2-aminobenzene sulfonate,
      OS) as the source(s) of nitrogen. The intracellular desulfonative enzyme did not
      degrade 3- or 4-aminobenzene sulfonates in the medium, although the enzyme in
      cell extracts degraded these compounds. We deduce the presence of a selective
      permeability barrier to sulfonates and conclude that the first step in sulfonate
      metabolism is transport into the cell. Cell-free desulfonation of BS in standard
      reaction mixtures required 2 mol of O2 per mol. One mol of O2 was required for a
      catechol 2,3-dioxygenase. When meta ring cleavage was inhibited with 3
      chlorocatechol in desalted extracts, about 1 mol each of O2 and of NAD(P)H per
      mol of BS were required for the reaction, and SO3(2-) and catechol were recovered
      in high yield. Catechol was shown to be formed by dioxygenation in an experiment
      involving 18O2. 4-Toluene sulfonate was subject to NAD(P)H-dependent
      dioxygenation to yield SO3(2-) and 4-methylcatechol, which was subject to meta
      cleavage. OS also required 2 mol of O2 per mol and NAD(P)H for degradation, and
      SO3(2-) and NH4+ were recovered quantitatively. Inhibition of ring cleavage with
      3-chlorocatechol reduced the oxygen requirement to 1 mol per mol of OS SO3(2-) (1
      mol) and an unidentified organic intermediate, but no NH4+, were observed.

PMID- 1368143
TI  - Effect of fluorinated analogues of phenol and hydroxybenzoates on the anaerobic
      transformation of phenol to benzoate.
AB  - The effects of fluorinated analogues on the anaerobic transformation of phenol to
      benzoate were examined. At greater than or equal to 250 microM 2- or 3
      fluorophenol, phenol transformation was delayed. 2-Fluorophenol had no apparent
      effect on subsequent degradation of benzoate, but benzoate accumulated in the
      presence of greater than or equal to 250 microM 3-fluorophenol. In contrast, 4
      fluorophenol at less than or equal to 2 mM had no effect on either phenol
      transformation or benzoate degradation. Phenol and 2-, or 3-fluorophenol were
      transformed simultaneously, but phenol was transformed more rapidly than either
      fluorophenol. Thus, fluorinated analogues of phenol did not prevent anaerobic
      transformation of phenol to benzoate. 2-Fluorophenol was converted to 3
      fluorobenzoate, and phenol enhanced the rate and extent of its transformation. 3
      Fluorophenol was transformed to 2-fluorobenzoate to a limited extent
      (approximately 3%) when phenol was present. 4-Fluorophenol was not transformed
      regardless of the presence of phenol. 3-Fluoro-4-hydroxybenzoate, a potential
      fluorinated intermediate product of para-carboxylation, was transformed rapidly
      to 2-fluorophenol and 3-fluorobenzoate, irrespective of the presence of phenol,
      indicating that both dehydroxylation and decarboxylation occurred. Initially, 2
      fluorophenol and 3-fluorobenzoate were rapidly formed in an approximate molar
      ratio of 2:1. Once 3-fluoro-4-hydroxybenzoate was completely removed, the 2
      fluorophenol, initially formed, was converted to 3-fluorobenzoate at a slower
      rate. Thus, phenol enhanced transformation of the fluorinated analogues, and the
      products of transformation suggested para-carboxylation. 3-Fluoro-2
      hydroxybenzoate was not transformed in either the presence or absence of phenol,
      indicating that ortho-carboxylation did not occur.

PMID- 1368144
TI  - Formation and physiological role of biosurfactants produced by hydrocarbon
      utilizing microorganisms. Biosurfactants in hydrocarbon utilization.
AB  - Microbial growth on water-insoluble carbon sources such as hydrocarbons is
      accompanied by metabolic and structural alterations of the cell. The appearance
      of surface-active compounds (biosurfactants) in the culture medium or attached to
      the cell boundaries is often regarded as a prerequisite for initial interactions
      of hydrocarbons with the microbial cell. Under this point of view, biosurfactants
      produced by hydrocarbon-utilizing microorganisms, their structures and physico
      chemical properties are reviewed. The production of such compounds is mostly
      connected with growth limitation in the late logarithmic and the stationary
      growth phase, in which specific enzymes are induced or derepressed. Addition of
      purified biosurfactants to microbial cultures resulted in inhibitory as well as
      in stimulatory effects on growth. Therefore, a more differentiated view of
      microbial production of surface-active compounds is proposed. Biosurfactants
      should not only be regarded as prerequisites of hydrocarbon uptake, but also as
      secondary metabolic products.

PMID- 1368145
TI  - Microbial degradation of chelating agents used in detergents with special
      reference to nitrilotriacetic acid (NTA).
AB  - The extensive use of phosphate-based detergents and agricultural fertilizers is
      one of the main causes of the world-wide eutrophication of rivers and lakes. To
      ameliorate such problems partial or total substitution of phosphates in laundry
      detergents by synthetic, non-phosphorus containing complexing agents is practiced
      in several countries. The physiological, biochemical and ecological aspects of
      the microbial degradation of the complexing agents most frequently used, such as
      polyphosphates, aminopolycarboxylates (especially of nitrilotriacetic acid), and
      phosphonates are reviewed.

PMID- 1368146
TI  - Physiology and performance of thermophilic microorganisms in sewage sludge
      treatment processes.

PMID- 1368147
TI  - The biodegradation of aromatic hydrocarbons by bacteria.
AB  - Aromatic compounds of both natural and man-made sources abound in the
      environment. The degradation of such chemicals is mainly accomplished by
      microorganisms. This review provides key background information but centres on
      recent developments in the bacterial degradation of selected man-made aromatic
      compounds. An aromatic compound can only be considered to be biodegraded if the
      ring undergoes cleavage, and this is taken as the major criteria for inclusion in
      this review (although the exact nature of the enzymic ring-cleavage has not been
      confirmed in all cases discussed). The biodegradation of benzene, certain arenes,
      biphenyl and selected fused aromatic hydrocarbons, by single bacterial isolates,
      are dealt with in detail.

PMID- 1368149
TI  - Physiology of aliphatic hydrocarbon-degrading microorganisms.
AB  - This paper reviews aspects of the physiology and biochemistry of the microbial
      biodegradation of alkanes larger than methane, alkenes and alkynes with
      particular emphasis upon recent developments. Subject areas discussed include:
      substrate uptake; metabolic pathways for alkenes and straight and branched-chain
      alkanes; the genetics and regulation of pathways; co-oxidation of aliphatic
      hydrocarbons; the potential for anaerobic aliphatic hydrocarbon degradation; the
      potential deployment of aliphatic hydrocarbon-degrading microorganisms in
      biotechnology.

PMID- 1368150
TI  - Microbial metabolism of monoterpenes--recent developments.
AB  - Monoterpenes are important renewable resources for the perfume and flavour
      industry but the pathways and enzymology of their degradation by microorganisms
      are not well documented. Until recently the acyclic monoterpene alcohols, (+)
      camphor and the isomers of limonene were the only compounds for which significant
      sections of catabolic pathways and associated enzymology had been reported. In
      this paper recent developments in our understanding of the enzymology of ring
      cleavage by microorganisms capable of growth with 1,8-cineole and alpha-pinene
      are described. 1,8-Cineole has the carbocyclic skeleton of a monocyclic
      monoterpene with the added complication of an internal ether linkage. Ring
      hydroxylation strategy and biological Baeyer-Villiger oxygenation lead to an
      efficient method for cleaving the ether linkage. alpha-Pinene is an unsaturated
      bicyclic monoterpene hydrocarbon. At least two catabolic pathways exist.
      Information concerning one of them, in which alpha-pinene may be initially
      converted into limonene, is rudimentary. The other involves attack at the double
      bond resulting in formation of alpha-pinene epoxide. Ring cleavage is then
      catalysed by a novel lyase that requires no additional components and breaks both
      carbocyclic rings in a concerted manner.

PMID- 1368148
TI  - Degradation of halogenated aromatic compounds.
AB  - Due to their persistence, haloaromatics are compounds of environmental concern.
      Aerobically, bacteria degrade these compounds by mono- or dioxygenation of the
      aromatic ring. The common intermediate of these reactions is (halo)catechol.
      Halocatechol is cleaved either intradiol (ortho-cleavage) or extradiol (meta
      cleavage). In contrast to ortho-cleavage, meta-cleavage of halocatechols yields
      toxic metabolites. Dehalogenation may occur fortuitously during oxygenation.
      Specific dehalogenation of aromatic compounds is performed by hydroxylases, in
      which the halo-substituent is replaced by a hydroxyl group. During reductive
      dehalogenation, haloaromatic compounds may act as electron-acceptors. Herewith,
      the halosubstituent is replaced by a hydrogen atom.

PMID- 1368151
TI  - Cytochrome P-450-dependent catabolism of triethanolamine in Rhodotorula
      mucilaginosa.
AB  - The yeast Rhodotorula mucilaginosa was able to grow in media containing
      triethanolamine or diethanolamine as the sole nitrogen source. During growth in
      the presence of triethanolamine, extracts of yeast cells contained increased
      levels of cytochrome P-450 dependent monooxygenase which catalyzed the oxidative
      N-dealkylation of aminoalcohols. Formation of diethanolamine, ethanolamine and
      glyoxylate from triethanolamine was demonstrated, and the identity of the
      products was verified by thin layer chromatography. These observations suggested
      the following scheme of triethanolamine catabolism: triethanolamine---
      diethanolamine + glycolaldehyde, diethanolamine----ethanolamine + glycolaldehyde,
      ethanolamine----NH3 + glycolaldehyde----glycolate----glyoxylate----glycerate
      pathway.

PMID- 1368152
TI  - Metabolism of naphthalene by the biphenyl-degrading bacterium Pseudomonas
      paucimobilis Q1.
AB  - Pseudomonas paucimobilis Q1 originally isolated as biphenyl degrading organism
      (Furukawa et al. 1983), was shown to grow with naphthalene. After growth with
      biphenyl or naphthalene the strain synthesized the same enzyme for the ring
      cleavage of 2,3-dihydroxybiphenyl or 1,2-dihydroxynaphthalene. The enzyme,
      although characterized as 2,3-dihydroxybiphenyl dioxygenase (Taira et al. 1988),
      exhibited considerably higher relative activity with 1,2-dihydroxynaphthalene.
      These results demonstrate that this enzyme can function both in the naphthalene
      and biphenyl degradative pathway.

PMID- 1368153
TI  - UAF radiorespirometric protocol for assessing hydrocarbon mineralization
      potential in environmental samples.
AB  - Following the EXXON Valdez oil spill, a radiorespirometric protocol was developed
      at the University of Alaska Fairbanks (UAF) to assess the potential for
      microorganisms in coastal waters and sediments to degrade hydrocarbons. The use
      of bioremediation to assist in oil spill cleanup operations required microbial
      bioassays to establish that addition of nitrogen and phosphorus would enhance
      biodegradation. A technique assessing 1-14C-n-hexadecane mineralization in
      seawater or nutrient rich sediment suspensions was used for both of these
      measurements. Hydrocarbon-degradation potentials were determined by measuring
      mineralization associated with sediment microorganisms in sediment suspended in
      sterilized seawater and/or marine Bushnell-Haas broth. Production of 14CO2 and
      CO2 was easily detectable during the first 48 hours with added hexadecane levels
      ranging from 10 to 500 mg/l of suspension and dependent on the biomass of
      hydrocarbon degraders, the hydrocarbon-oxidation potential of the biomass and
      nutrient availability. In addition to assessment of the hydrocarbon-degrading
      potential of environmental samples, the radiorespirometric procedure, and
      concomitant measurement of microbial biomass, has utility as an indicator of
      hydrocarbon contamination of soils, aqueous sediments and water, and can also be
      used to evaluate the effectiveness of bioremediation treatments.

PMID- 1368154
TI  - Dichloromethane utilized by an anaerobic mixed culture: acetogenesis and
      methanogenesis.
AB  - Dichloromethane (8.9 mg/l) was eliminated from industrially polluted, anaerobic
      groundwater in a fixed-bed reactor (43 m3) which was packed with activated
      charcoal and operated continuously for over three years. The elimination of
      dichloromethane over this period was some ten-fold in excess of the sorptive
      capacity of the charcoal, and the elimination (3.7 mg/h.[kg of charcoal]:
      residence time, 49 h) was tentatively attributed to dehalogenative microorganisms
      immobilized on the charcoal. Anaerobic enrichment cultures, with dichloromethane
      as the sole added source of carbon and energy, were inoculated with material from
      the reactor. Reproducibly complete substrate disappearance in subcultures was
      observed when traces of groundwater (1%) or yeast extract (0.01%) were supplied.
      Fed-batch experiments under an atmosphere of CO2 plus N2 led to the conversion in
      11 days of 11 mM dichloromethane to 3 mM acetate and 2 mM methane, with a growth
      yield of 0.4 g of protein/mol of dichloromethane; insignificant amounts (less
      than 1 microM) of chloromethane accumulated. Methanogenesis could be inhibited by
      50 mM 2-bromoethane sulfonate without any effect on the dehalogenation rate. The
      maximum dehalogenation rate was 0.13 mmol dichloromethane/h.l (2.6 mkat/kg of
      protein).

PMID- 1368155
TI  - Ether-cleaving enzyme and diol dehydratase involved in anaerobic polyethylene
      glycol degradation by a new Acetobacterium sp.
AB  - A strictly anaerobic, homoacetogenic bacterium was enriched and isolated from
      anoxic sewage sludge with polyethylene glycol (PEG) 1000 as sole source of carbon
      and energy, and was assigned to the genus Acetobacterium on the basis of
      morphological and physiological properties. The new isolate fermented ethylene
      glycol and PEG's with molecular masses of 106 to 1000 to acetate and small
      amounts of ethanol. The PEG-degrading activity was not destroyed by proteinase K
      treatment of whole cells. In cell-free extracts, a diol dehydratase and a PEG
      degrading (ether-cleaving) enzyme activity were detected which both formed
      acetaldehyde as reaction product. The diol dehydratase enzyme was oxygen
      sensitive and was stimulated 10-14 fold by added adenosylcobalamine. This enzyme
      was found mainly in the cytoplasmic fraction (65%) and to some extent (35%) in
      the membrane fraction. The ether-cleaving enzyme activity reacted with PEG's of
      molecular masses of 106 to more than 20000. The enzyme was measurable optimally
      in buffers of high ionic strength (4.0), was extremely oxygen-sensitive, and was
      inhibited by various corrinoids (adenosylcobalamine, cyanocobalamine,
      hydroxocobalamine, methylcobalamine). This enzyme was found exclusively in the
      cytoplasmic fraction. It is concluded that PEG is degraded by this bacterium
      inside the cytoplasm by a hydroxyl shift reaction, analogous to a diol
      dehydratase reaction, to form an unstable hemiacetal intermediate. The name
      polyethylene glycol acetaldehyde lyase is suggested for the responsible enzyme.

PMID- 1368156
TI  - Dynamic response of naphthalene biodegradation in a continuous flow soil slurry
      reactor.
AB  - Periodic perturbations were used to evaluate the system stability and robustness
      of naphthalene biodegradation in a continuous flow stirred tank reactor (CSTR)
      containing a soil slurry. The experimental design involved perturbing the test
      system using a sinusoidal input either of naphthalene or non-naphthalene organic
      carbon at different frequencies during steady state operation of the reactors.
      The response of the test system was determined by using time series off-gas
      analysis for naphthalene liquid phase concentration and degradation, total viable
      cell counts, and gene probe analysis of naphthalene degradative genotype, and by
      batch mineralization assays. Naphthalene biodegradation rates were very high
      throughout the experimental run (95 to greater than 99% removed) resulting in
      very low or undetectable levels of naphthalene in the off-gas and reactor
      effluent. Attempts to reduce the rate of naphthalene biotransformation by either
      reducing the reactor temperature from 20 degrees C to 10 degrees C or the
      dissolved oxygen level (greater than 1 mg/L) were unsuccessful. Significant
      naphthalene biodegradation was observed at 4 degrees C. While variable, the
      microbial community as measured by population densities was not significantly
      affected by temperature changes. In terms of naphthalene biotransformation, the
      system was able to adapt readily to all perturbations in the reactor.

PMID- 1368157
TI  - Dye-ligand centrifugal affinity chromatography.
AB  - A fast method for the screening of a large number of immobilized dyes for the
      purification or binding of proteins called dye-ligand centrifugal affinity
      chromatography, is described. The ease and speed of this method is demonstrated
      by screening 65 immobilized dyes for the binding of purified goat IgG. Two
      immobilized dyes (Drimarene Blue K-R and Drimarene Rubine R/K-5BL) with a high
      affinity for goat IgG were found to bind specifically the Fc-fragment of the IgG.

PMID- 1368158
TI  - Differential salt-promoted chromatography for protein purification.
AB  - A range of hydrophobic-type adsorbents for protein chromatography has been
      screened for the binding, at high salt concentrations, of 10 enzymes from a
      bacterial extract. Adsorbents were chosen for tandem chromatography, in which the
      first adsorbent removed much of the protein, and the second and subsequent
      columns bound the desired enzymes. Simple schemes for isolating Zymomonas mobilis
      and yeast alcohol dehydrogenases are described, in which the enzymes are affinity
      eluted by NAD+.

PMID- 1368159
TI  - An improved purification procedure of alkaline phosphatase from calf intestine by
      applying partition in aqueous two-phase systems and dye-ligand chromatography.
AB  - Aqueous two-phase partitioning has been elaborated in order to improve the
      purification of alkaline phosphatase from calf intestine in larger scale. The
      laborious precipitation and centrifugation steps for the removal of the enzyme
      from the cell debris and from the bulk protein were replaced by this technique
      yielding a high recovery (88%) and a significant lower time requirement. For the
      preparation of 100.000 units (46 mg) of a homogeneous enzyme 2.0 kg of a system
      containing 200 g PEG 4000 and only 10 g dextran M 70 is necessary. Affinity
      partitioning in aqueous two-phase systems was used to screen 41 dyes for
      selecting a suitable ligand for the dye-ligand chromatography of the enzyme. In
      the case of alkaline phosphatase the results obtained by affinity partitioning
      coincide with the experimental requirements for the affinity chromatography of
      the enzyme. Procion Navy HE-R (Blue 171) exhibits a high affinity, selectivity
      and binding capacity for the enzyme compared with other dyes investigated. The
      purification procedure provided the same degree in purity (2200 U/mg) and yield
      (59%) if mucosa or chyme was applied as starting material. In the range of
      practical use the purified enzyme contains no detectable activities of DNAses
      (endonucleases) and DNA-nicking activities. The contamination with
      phosphodiesterase I (EC. 3.1.4.1.) is less than 0.01%.

PMID- 1368161
TI  - A simplified process for large-scale isolation of IgG from goat serum.
AB  - Immunoglobin G (IgG) is routinely used in many immunoassay systems. Whilst
      various laboratory-scale procedures exist for the isolation of IgG from host
      serum few are appropriate for scale-up. We have previously reported the
      improvement of an existing process for isolation of IgG from goat serum at
      laboratory scale (Schwartz et al., 1986) and in this study we took those
      improvements to pilot-scale and significantly reduced the process time and
      associated costs. Media fouling was reduced and product yield enhanced by
      utilisation of a guard column of the appropriate geometry. Isolation of pure IgG
      by anion-exchange chromatography was improved by selection of a suitable mobile
      phase and column loading parameters. Using a 10 1 column of QA52, 36 g of
      immunoelectrophoretically pure IgG was isolated from 7.2 1 of goat serum at an
      overall yield of 58%. Product recovery and purity were reproducible at pilot
      scale under these conditions. A procedure for media clean-in-place (CIP) is
      described which also effects sterilisation and depyrogenation of the column and
      media.

PMID- 1368160
TI  - Comparative studies of agarose and kieselguhr-agarose composites for the
      preparation and operation of immunoadsorbents.
AB  - Study was made of controlled fabrication and operation of immunoadsorbents
      exploiting beaded composites of agarose or kieselguhr-agarose. Materials were
      activated by cyanogen bromide and tresyl chloride, derivatised with human IgG
      antigens, and utilised in direct, one-step purifications of anti-huIgG monoclonal
      antibodies produced in serum-based cultures of murine hybridomas. The influence
      of solid phase composition, degrees of activation, concentration of immobilised
      antigen, capping chemistries, and mode of product desorption was studied in
      respect of purification performance. Maximum concentrations of immobilised huIgG
      could be achieved following activation of 50% available hydroxyl groups in both
      materials. Specific adsorption and desorption of monoclonal antibodies, expressed
      per mole of immobilised ligand, declined with increasing ligand concentrations.
      Control of activation and derivatisation of agarose solid phases enhanced the
      overall specification and performance of both homogeneous and composite
      fabricates. The large particle size of composites (150-1000 microns) restricted
      efficient performance in fixed bed contactors operated under non-equilibrium
      conditions. However, their physical nature recommended adsorptive operations with
      particulate feedstocks in fixed or fluidised beds, batch suspension contactors,
      or fast flow regimes adopted for cleaning and equilibration operations.

PMID- 1368162
TI  - Restricted diffusion of molecules in porous affinity chromatography adsorbents.
AB  - A restricted diffusion model is constructed and solved in order to study the
      permeability of large adsorbate molecules in the pores of affinity chromatography
      media, when the adsorbate molecules are adsorbed onto immobilized ligands. The
      combined effects of steric hindrance at the entrance to the pores and frictional
      resistance within the pores, as well as the effects of pore size distribution,
      pore connectivity of the adsorbent, molecular size of adsorbate and ligand, and
      the fractional saturation of adsorption sites (ligands), are considered. Affinity
      adsorbents with dilute and high ligand concentrations are examined, and the
      permeability of the adsorbate in porous networks of connectivity nT is studied by
      means of effective medium approximation (EMA) numerical solutions. As expected,
      the permeability of the adsorbate decreases as the size of the adsorbate and/or
      ligand molecule increases. The permeability also decreases when the fractional
      saturation of the ligands increases, as well as when the pore connectivity of the
      network decreases. The dependence of the permeability on the pore connectivity
      tends to be less marked in adsorbents with concentrated ligand than in porous
      media with dilute ligand concentration. The conditions are also presented for
      which the percolation threshold is attained in a number of different systems. The
      restricted diffusion model and results of this work may be of importance in
      studies involving the modeling, prediction of the dynamic behavior, design, and
      control of affinity chromatography (biospecific adsorption) systems employing
      porous adsorbents. The theoretical results may also have important implications
      in the selection of a ligand as well as in the selection and construction of an
      affinity porous matrix, so that the adsorbate of interest can be efficiently
      separated from a given solution. Furthermore, with appropriate modifications this
      restricted diffusion model may be used in studies involving the immobilization of
      ligands or enzymes in porous solids.

PMID- 1368163
TI  - Optimization and simulation of continuous affinity-recycle extraction (care).
AB  - Simulation and optimization of continuous affinity recycle extraction (CARE), a
      protein purification unit operation based on protein adsorption to solid phase
      adsorbents, is described in this paper. Rather than packing conventional
      adsorbent particles in a fixed bed (column), solid/liquid contact is carried out
      in well-mixed reactors. Continuous operation is achieved by recirculation of the
      adsorbent particles between two or more contactors. The feasibility of this
      purification scheme was established with the recovery and isolation of the enzyme
      beta-galactosidase from E.coli, using the affinity support PABTG/Agarose. A
      mathematical model describing system performance was developed. The mathematical
      model was used to optimize several facets of the system design and operation. The
      base two-stage contractor design was modified by the addition of an intermediate
      wash stage as well as the incorporation of multiple adsorption stages. These
      design modifications serve to increase purification, concentration and recovery
      while utilizing the same amount of adsorbent. The methodology for defining and
      optimizing objective functions was developed and experimentally validated.
      Finally, optimum system start-up protocols, minimizing the time required to reach
      steady-state operation, were developed and experimentally validated. The impact
      of early introduction of adsorptive purification in a downstream processing
      sequence, with CARE, was evaluated and is described. Through the early
      introduction of a highly specific adsorptive step, significant purification is
      achieved simultaneously with clarification and concentration. In addition,
      purification performance in CARE was contrasted with that achievable in
      conventional column chromatography.

PMID- 1368164
TI  - Fast electrotransfer of human serum proteins in their native state from
      polyacrylamide thin gradient gels reinforced by textiles to polyvinylidene
      difluoride membranes. Rapid electrotransfer from thin gradient gels reinforced by
      textiles.
AB  - A fast electroblotting technique of native molecules electrophoretically
      separated in thin (0.25 to 0.5 mm) gradient gels, onto a high capacity membrane
      of polyvinylidene difluoride is described. Omitting methanol during transfer, the
      equilibration step is avoided and the same buffer is used in electrophoresis and
      transfer. As the gel reinforced by fabric never swells nor shrinks, and as all
      the bands are blotted, the transfer matrix exactly reflects the protein pattern
      of the original gel. Autoradiography is enhanced and electroelution is
      homogeneous in all parts of the gels. Significant improvement is noticed in
      binding proteins of molecular weight from about 20 kDa to more than 700 kDa, as
      suggested by complete electroelution of all native serum components.

PMID- 1368165
TI  - Protein/enzyme inactivation during different chromatographic methods of
      separation.
AB  - Protein denaturations encountered during the different types of chromatographic
      separations are presented. The analysis of different protein denaturations
      presented along with the causes of such denaturations provides a judicious
      framework to compare protein denaturations encountered by such separation
      techniques. Especially of interest are those studies which compare the mass
      recovery of proteins and the retention of activity by different chromatographic
      techniques. Reversed-phase chromatography is presented even though it is utilized
      nowadays only for specialized cases such as separation of small peptides. It
      appears that relatively mild interactions that are encountered generally in
      hydrocarbon-interaction chromatography are favorable to the preservation of the
      native (active) protein state. The few available mechanistic studies presented
      provide judicious physical insights into protein conformational behavior on
      chromatographic columns.

PMID- 1368166
TI  - Chromatography of hen egg-white proteins on anion-exchange cellulose at high flow
      rates using a radial flow column.
AB  - The influence of column configuration on the separation of hen egg-white proteins
      using Whatman DE52 and QA52 anion-exchange cellulose has been investigated. Using
      a 100 ml volume axial flow column (6.6 cm x 4.4 cm i.d.) we achieved flow rates
      of up to 25 ml/min i.e. 15 bed volumes/h after which higher flow was restricted
      due to pressure constraints within the system. Under radial flow conditions using
      a 100 ml column flow rates of up to 150 ml/min i.e. 90 bed volumes/h were
      achieved using DE52 and QA52. While chromatographic resolution was superior under
      axial flow at the lower flow rates excellent resolution was maintained at up to
      150 ml/min using the radial flow column. This is a consequence of the fast
      kinetics of adsorption/desorption exhibited by DE52 and QA52. The data indicate
      that it is the column configuration and not the cellulose matrix which influences
      flow performance.

PMID- 1368167
TI  - Immunoaffinity chromatography of enzymes.
AB  - Immunoaffinity chromatography of enzymes represents an attractive purification
      technique suitable for one-step and large-scale purification of enzymes to
      homogeneity. Monoclonal and polyclonal antibodies can be used equally well. The
      broad use of the technique is restricted by the harsh elution conditions which
      are often required. The efforts to overcome these limitations and to optimize the
      method are reviewed, viz. proenzyme purification, purification of enzymes as part
      of multienzyme complexes carried out by a mild dissociation step, specific
      elution by substrates and effectors, enzyme stabilization, electrophoretical
      desorption and negative elution by adsorbing impurities from the crude extract,
      and hypotonic elution. The current practice is discussed considering antibody and
      enzyme selection, optimization of elution conditions, and washing steps using
      different media. Representative examples are given for various approaches.

PMID- 1368168
TI  - Trends and future prospects of aqueous two-phase extraction.
AB  - Aqueous two-phase systems form the basis for an extraction technology of
      proteins. Trends in the development of the technology are reviewed and discussed
      with regard to future applications.

PMID- 1368169
TI  - On protein partitioning in two-phase aqueous polymer systems.
AB  - The partitioning of proteins between the coexisting phases of two-phase aqueous
      polymer systems reflects an intricate and delicate balance of interactions
      between proteins, polymers, salts and water. Experimental investigations have
      suggested that a large number of factors influence protein partitioning,
      including the types of polymers, their molecular weight and concentration; the
      protein sizes, conformation and composition; salt type and concentration, and
      solution pH; and the presence of ligands attached to the polymer which may
      interact with surface sites of the protein. Complementary modelling attempts have
      been successful in illuminating several molecular-level mechanisms influencing
      protein partitioning using lattice-model techniques, viral expansions and a
      scaling-thermodynamic approach. In spite of these experimental and modelling
      approaches, many of the physical phenomena associated with these complex systems
      are not well understood. Notably, the precise nature of the protein-polymer
      interactions and the potent effect of inorganic salts on the partitioning of
      proteins in these systems remains poorly understood.

PMID- 1368170
TI  - Statistical thermodynamics of phase separation and ion partitioning in aqueous
      two-phase systems.
AB  - A general model for the phase behavior of polymer-polymer aqueous two-phase
      systems containing small amounts of added inorganic salts has been developed from
      statistical thermodynamics. The model is based on the solution theory of Hill and
      new electrolyte solution model based on Fluctuation Solution Theory. It includes
      the effect of polymer molecular weight with scaling expressions from the
      Renormalization Group theory of polymer solutions. The model has been used to
      calculate the phase diagram and the partitioning of salt for an aqueous two-phase
      system containing polyethylene glycol (MW = 8000) and dextran (MW = 28,700) with
      0.1 mole/kg of added Na2SO4. The calculations have been compared to experimental
      results with good agreement.

PMID- 1368171
TI  - Affinity partitioning and extraction of proteins.
AB  - Affinity partitioning of enzymes and plasma proteins in aqueous two-phase systems
      has been reviewed. Besides basic theoretical considerations of the principle of
      affinity partitioning the chemistry of coupling ligands to the polymers, the
      nature and properties of selected biomimetic ligands like dye-ligands,
      immunoligands, metal chelate ligands and hydrophobic ligands are reported. The
      usefulness of affinity partitioning for studying the affinity of ligands and
      their specificity to proteins has been demonstrated by selected examples. The
      method proved also applicable to study the structural dynamics of proteins as
      exemplified with phosphofructokinase from baker's yeast and human alpha-2
      macroglobulin. The current knowledge of metal chelate affinity partitioning is
      presented as well as the applicability of affinity partitioning for the
      purification of enzymes.

PMID- 1368172
TI  - Aqueous two-phase systems for biotechnical use.
AB  - The different kinds of aqueous two-phase systems for accepted or potential use in
      biotechnology are summarized. Some properties of interest for the extractive use
      are discussed.

PMID- 1368173
TI  - Liquid-liquid partition chromatography of biopolymers in aqueous two-phase
      systems.
AB  - The theoretical and practical principles of liquid-liquid partition
      chromatography (LLPC) applying aqueous two-phase polymer systems are presented.
      The method is based on support materials which bind one of the two aqueous phases
      with high preference and reject the other. This selectivity is obtained by making
      use of incompatibilities between polymers grafted on support particles and
      polymers in solution. Applications of the separation technique to the
      fractionation of protein and nucleic acid mixtures are shown. For the DNA
      fractionation according to base composition an affinity partition chromatography
      using polyethylene glycol-bound base-specific complexing agents has been
      developed which exhibits a resolution superior to all other methods known.

PMID- 1368174
TI  - Aqueous two-phase extraction of plant enzymes from sources containing large
      amounts of tannins and anionic mucilages.
AB  - The isolation of plant enzymes is frequently hampered by the presence of phenolic
      compounds, pigments and mucilages. Recently, extraction procedures based on
      aqueous two-phase systems were used to overcome these problems. Two-phase systems
      have a great advantage in respect to yield, product purity and processing time.
      Two-phase systems may open many new avenues in research as well as for
      application of enzymes from plant material, especially making available enzymes
      of sources avoided till now, due to the difficulties to work with.

PMID- 1368175
TI  - Extraction of proteins from animal tissue using multiphase aqueous systems.
AB  - Animal tissue is likely to continue to be an important source of enzymes and
      protein hormones well into the 21st century. Aqueous phase systems show
      considerable potential and specific advantages for extractive purification of
      proteins from animal tissue. Although no industrial process is yet in place for
      commercial production of a protein from animal tissue, the potential for the
      system has, however, been demonstrated at laboratory scale for a number of
      enzymes, and at pilot scale for a few, using simple phase systems and also
      affinity partitioning systems. Pertinent features of these systems are reviewed,
      and process and economic aspects discussed.

PMID- 1368176
TI  - Combined use of extraction and genetic engineering for protein purification:
      recovery of beta-galactosidase fused proteins.
AB  - Partitioning of beta-galactosidase in aqueous two-phase systems of poly(ethylene
      glycol) and potassium phosphate is reviewed. The affinity of Escherichia coli
      beta-galactosidase for the PEG-rich phase dominates also in beta-galactosidase
      fusion proteins and the concept of using beta-galactosidase as an affinity handle
      for extraction of other proteins, after fusion, is discussed. A hypothesis is
      presented, assuming that tryptophan residues at the surface of beta-galactosidase
      is responsible for its partitioning to the PEG rich phase, and the concept of
      poly-tryptophan handles fused to the target protein for extraction is introduced.

PMID- 1368178
TI  - Mycoplasmal contamination and control.

PMID- 1368177
TI  - Continuous counter-current two-phase aqueous extraction.
AB  - Continuous counter-current column operation provides operating convenience for
      contacting two-phase aqueous partitioning systems for protein extraction. We
      discuss in detail the important parameters for designing spray, packed, plate and
      York-Scheibel columns for protein recovery using both polymer-polymer and polymer
      salt two-phase aqueous systems. We compare the various contractors for their
      operating and extraction efficiency. The work also provides a step-by-step design
      procedure and specific recommendations for future data needs.

PMID- 1368179
TI  - Adjuvants: the key to enhanced immune responses.

PMID- 1368180
TI  - Use of modified polystyrene microwells to enhance immunoassay sensitivity.

PMID- 1368181
TI  - Genes for phosphonate biodegradation in Escherichia coli.
AB  - Escherichia coli has a carbon-phosphorus (C-P) lyase with a broad substrate
      specificity, whose synthesis is induced many hundred fold during phosphate (Pi)
      limitation. Fourteen genes for phosphonate metabolism comprise the phnC-to-phnP
      gene cluster: three gene products (PhnC, PhnD, and PhnE) comprise a binding
      protein-dependent phosphonate transporter, which also transports Pi and phosphate
      esters; two gene products (PhnF and PhnO) may have a role in gene regulation; and
      nine gene products (PhnG, PhnH, PhnI, PhnJ, PhnK, PhnL, PhnM, PhnN, and PhnP) may
      comprise a C-P lyase enzyme complex. Phosphonate biodegradation via a C-P lyase
      appears to be limited by the specificity of the PhnCDE transporter and not by the
      specificity of the C-P lyase. These interpretations are based on results from a
      combination of molecular genetic and molecular biological studies on phosphonate
      metabolism in E. coli.

PMID- 1368182
TI  - Identification and nucleotide sequence of the leukocyte and reticulocyte forms of
      rabbit cytochrome b5 mRNA.
AB  - RNA extracted from rabbit leukocytes and reticulocytes was reverse transcribed
      and used in the Polymerase Chain Reaction technique along with primers designed
      to amplify the coding sequence of rabbit cytochrome b5. The resultant amplified
      products were subcloned and analyzed. Sequencing confirmed that leukocyte and
      liver cDNAs are homologous and encode the membrane-bound form of the protein. In
      contrast, reticulocytes exhibit a highly similar, but different mRNA which
      encodes the smaller, soluble cytochrome b5. This is the first example of a
      cytochrome b5 sequence from a tissue other than liver, erythrocyte or
      reticulocyte.

PMID- 1368183
TI  - Role of protein methylation in agonist-induced signal transduction in human
      platelets.
AB  - Possible role of methylation of proteins in platelet activation was examined in
      this study. Electropermeabilized platelets incorporated radioactivity in the
      presence of [methyl-3H]-S-adenosylmethionine. Thrombin, PDBu and GTP gamma S
      increased incorporation of radioactivity in a time-dependent manner. In other
      experiments, 23 kD membrane proteins incorporated radioactivity in the presence
      of [methyl-3H]-S-adenosylmethionine and platelet cytosol. Using rap specific
      antisera the 23 kD methylated proteins were characterized as low Mr G proteins,
      known as rap1 proteins. N-Acetyl-S-farnesyl-L-cysteine (AFC), an inhibitor of the
      methyltransferase, inhibited carboxyl methylation of platelet rap1 proteins and
      also inhibited platelet aggregation and mobilization of cytosolic calcium induced
      by a variety of agonists in a concentration-dependent manner. Inhibition of
      methylation of rap1 proteins as well as inhibition of platelet activation by AFC
      suggests that methylation and consequently translocation of rap1 proteins to
      plasma membrane may be important for agonist-induced signal transduction in human
      platelets.

PMID- 1368184
TI  - Two flavonol glycosides from seeds of Camellia sinensis.
AB  - Two novel flavonol triglycosides, camelliaside A and B, have been isolated from
      seeds of Camellia sinensis. The structures were determined to be kaempferol 3-O
      [2-O-beta-D- galactopyranosyl-6-O-alpha-L-rhamnopyranosyl]-beta-D-glucopyranoside
      and kaempferol 3-O-[2-O-beta- D-xylopyranosyl-6-O-alpha-L-rhamnopyranosyl]-beta-D
      glucopyranoside on the basis of spectroscopic, chemical and enzymatic studies.
      These types of interglycosidic linkages, Gal(1----2)[Rha(1----6)]Glc and Xyl(1---
      2)[Rha(1----6)]Glc, have not been reported previously in flavone and flavonol
      glycosides.

PMID- 1368185
TI  - In hot pursuit of an HIV vaccine.

PMID- 1368186
TI  - Closing the culture gap.

PMID- 1368188
TI  - Fishing for microbes.

PMID- 1368187
TI  - Identifying transcribed sequences: the state of the art.

PMID- 1368189
TI  - Are isolated genes "useful"?

PMID- 1368190
TI  - Surface-active compounds from microorganisms.
AB  - Microbial surfactants are a structurally diverse group of compounds consisting of
      hydrophilic and hydrophobic domains and which partition preferentially at
      interfaces. Biosurfactants are of increasing interest commercially as substitutes
      for synthetic surfactants particularly for environmental applications. This
      article discusses recent progress in the genetic and biochemical analysis of
      biosurfactant synthesis as well as the current status of fermentation
      technologies.

PMID- 1368191
TI  - Production and functional characterization of a recombinant fragment of von
      Willebrand factor (vWF): an antagonist to platelet receptor GP Ib.
AB  - We expressed a recombinant peptide fragment (Ser445-Val733) of human von
      Willebrand factor (vWF), containing the binding domain for the platelet receptor
      of GP Ib, in E. coli. This 33 kD peptide blocks binding of the intact vWF
      molecule to GP Ib in the presence of modulators. Thus, it offers potential as an
      antithrombotic agent. High level expression was achieved in a plasmid construct
      driven by the bacteriophage T7 promoter. The peptide was solubilized from
      inclusion bodies in strong chaotrope, then reduced and alkylated. Following
      purification, formulation at pH 3.5, and lyophilization, the reconstituted
      experimental product (RG 12986) exists as an equilibrium of monomer and dimer
      species. When formulated above pH 5.0, soluble aggregates are formed; these
      solutions have less bioactivity than RG 12986. Interestingly, the non-aggregated
      state of RG 12986 remains conserved following dilution and incubation with
      platelet-poor plasma. The overall purification/low pH formulation strategies may
      be applicable to other E. coli recombinant proteins having a tendency to
      aggregate following removal of chaotrope near physiologic pH when in a
      concentrated format.

PMID- 1368192
TI  - High speed automated DNA sequencing in ultrathin slab gels.
AB  - We have developed a high speed instrument for automated DNA sequence analysis.
      The apparatus employs laser excitation and a cooled CCD detector for the parallel
      detection of up to 18 sets of four fluorescently labeled DNA sequencing reactions
      during their electrophoretic separation in ultrathin (50-100 microns) denaturing
      polyacrylamide gels. Four hundred and fifty bases of sequence information is
      obtained from 100 ng of M13 template DNA in less than one hour, corresponding to
      an overall instrument throughput of over 8000 bases/hr.

PMID- 1368194
TI  - Antibody assisted protein refolding.
AB  - In this study, we provide an initial demonstration of the use of monoclonal
      antibodies (MAbs) to enhance the yield of native protein during protein
      refolding. The presence of an anti-native MAb was found to enhance the refolding
      of reduced S-Protein (a fragment of Ribonuclease A) by as much as 360 percent
      over controls. This increase in recovered enzymatic activity was directly related
      to the MAb concentration and was saturable with excess antibody, suggesting that
      the antibodies are assisting through direct interaction at specific epitopes.

PMID- 1368193
TI  - Saccharomyces cerevisiae cells secreting an Aspergillus niger beta-galactosidase
      grow on whey permeate.
AB  - We describe the construction of a lactose-utilizing Saccharomyces cerevisiae that
      expresses the cDNA for a secreted, thermostable beta-galactosidase (lacA) from
      Aspergillus niger. Yeast cells expressing the lacA gene from the yeast ADH1
      promotor on a multicopy plasmid secrete up to 40% of the total beta-galactosidase
      activity into the growth medium. The secreted product is extensively N
      glycosylated, and cells expressing the lacA gene grow on whey permeate (4% w/v
      lactose) with a doubling time of 1.6 hours. Such strains may offer a solution to
      the increasing problem of waste whey disposal.

PMID- 1368195
TI  - Production of vitamins, coenzymes and related biochemicals by biotechnological
      processes.
AB  - Vitamins and related biofactors belong to those few chemicals with a direct
      positive appeal to people. There is indeed a large need for extra vitamins, other
      than those derived from plant and animal food sources, due to unbalanced food
      habits or processing, food shortage or disease. Added vitamins are now either
      prepared chemically or biotechnologically via fermentation or bioconversion
      processes. Several vitamins and related biofactors are now only or mainly
      produced chemically (vitamin A, cholecalciferol (D3), tocopherol (E), vitamin K2,
      thiamine (B1), niacin (PP or B3), pantothenic acid (B5), pyridoxine (B6), biotin
      (H or B8), folic acid (B9) or via extraction processes (beta-carotene or
      provitamin A, provitamin D3, tocopherol, vitamin F-group). However, for several
      of these compounds microbiological or algal methods also exist or are rapidly
      emerging. Others are produced practically exclusively via fermentation
      (ergosterol or provitamin D2, riboflavin (B2), cyanocobalamin (B12), orotic acid
      (B13), vitamin F-group, ATP, nucleosides, coenzymes, etc. or via microalgal
      culture (beta-carotene, E, F). Both chemical and microbial processes are run
      industrially for vitamin B2 while vitamin C (ascorbic acid) is produced via a
      combination of chemical reactions and fermentation processes. A survey is given
      here of the current state of vitamin production, with emphasis on developments
      and strategies for improved biotechnological production and its significance, as
      compared to existing chemical processes. The screening or construction of vitamin
      hyperproducing microbial strains is a difficult task; pathway elucidation and
      metabolic (de)regulation need further study; r-DNA technology has only recently
      been introduced; improved fermentation processes and immobilised biocatalysts
      bioconversions for the synthesis of chiral vitamin compounds or intermediates or
      derivatives are gaining importance; the recovery and purification of these
      vitamin compounds from their fermentation broths remains equally complex.

PMID- 1368196
TI  - Synthesis and antibacterial activity of certain quinoline and quinazoline
      derivatives containing sulfide and sulfone moieties.
AB  - Some aryl and/or heterocyclic mercaptans were allowed to react with 8-quinolyl
      chloroacetate (II), 8-quinolinoxyacetyl chloride (IV) and 3-(2'-chloroethyl)-2
      methyl-3,4-dihydroquinazolin-4-one (X) in dry benzene and/or sodium hydroxide in
      absolute ethanol to give corresponding 8-quinolyl-alpha-mercaptoacetate (V), 8
      quinolinoxythioacetate (VI) and 3-(2'-arylmercaptoethyl)-2-methyl-4
      (3H)quinazolin-4-ones or 3-(2'-heterocyclicmercaptoethyl)-2-methyl-4(3H)
      quinazolin-4 -ones (XIa-h). The mercaptans V and XI were subjected to oxidation
      with hydrogen peroxide/acetic acid mixture (1:2) to afford the corresponding
      sulfones VII and XII. The structures of the synthesized compounds were elucidated
      by spectroscopic (IR and 1H-NMR) and elemental analyses. Some of these compounds
      were tested for their antimicrobial activities in comparison with tetracycline as
      a reference compound.

PMID- 1368197
TI  - Flow injection analysis with immobilized enzymes for process control of pullulan
      production by fermentation.
AB  - A flow injection system is described for the parallel determination of pullulan
      and glucose during a fermentation of the fungus Aureobasidium pullulans. The
      polysaccharide was hydrolyzed by pullulanase and amyloglucosidase, immobilized to
      controlled-pore glass (CPG). The glucose produced was oxidized by glucose
      dehydrogenase and the NADH formed determined photometrically. The pullulan
      concentration was calculated from the difference to the response obtained for
      free glucose. The calibration curves for monomer and polymer were both linear
      between 2 mg dm-3 and 20 mg dm-3. Analysis of one sample for the determination of
      glucose and pullulan took about 10 min.

PMID- 1368198
TI  - Optimum culture conditions for the epoxidation of cis-propenylphosphonate to
      fosfomycin by Cellvibrio gilvus.
AB  - Approximately 470 strains of various microorganisms were tested for their ability
      to epoxidize cis-propenylphosphonate (PPOH) to (-)-cis-1,2-epoxypropylphosphonate
      (fosfomycin, FOM). Cellvibrio gilvus KY 3412 was selected as the best strain. To
      obtain higher activity, FOM-resistant strains were derived by N-methyl-N'-nitro-N
      nitrosoguanidine mutagenesis. Mutant KY 3413, showing ten times higher FOM
      resistance, was selected. The conditions for the conversion of PPOH to FOM during
      the cultivation of the mutant were optimized. The addition of both cobalt and
      vanadium ions to the culture medium greatly stimulated the conversion.
      Furthermore, when the pH was maintained at pH 8.0 during cultivation, the highest
      conversion was attained. The molar conversion yield of FOM was inversely
      dependent on the initial concentration of PPOH, that is, conversions of 100% at
      less than 0.05% PPOH and of 40% at 0.5% PPOH were attained after 5 days
      cultivation.

PMID- 1368200
TI  - A model for penicillin production with and without temperature shift after the
      growth phase.
AB  - A strain of Penicillium chrysogenum producing about 8 milligrams/l of penicillin
      V, was cultivated in a 10-1 bioreactor. Under carbon (C)-limitation during the
      production phase a glucose/ammonium sulphate mixture was fed using microprocessor
      control. When the temperature was shifted from 25 degrees C to 30 degrees C at
      the end of the active growth phase, the specific penicillin production rate was
      increased by 30%, while the yield remained constant. Maximal productivity without
      sporulation was obtained when the net growth rate of the active (respiring and
      producing) biomass, estimated by measuring the respiration rate under defined
      conditions, was equal to or higher than 0.004 h-1. A model was developed for
      penicillin fermentation during C-limitation possessing the following properties:
      (1) the model is based on ordinary differential equations; (2) the influence of
      different nutrients is considered; (3) the model recognizes two cell types
      (active and inactive); (4) the model describes the influence of a temperature
      shift at the end of the vigorous growth phase.

PMID- 1368199
TI  - Nutritional control of nikkomycin and juglomycin production by Streptomyces
      tendae in continuous culture.
AB  - Continuous cultures with Streptomyces tendae revealed some interesting facts. In
      a continuous culture running for more than 2500 h the production of either
      nikkomycines or juglomycins could be selected by varying the feed composition.
      Decreasing the phosphate supply in the feed broth from the initial concentration
      of 2.5 mM to 1.0 mM enhanced the productivity of nikkomycins and decreased the
      productivity of juglomycins. When switching back to the initial conditions of the
      experiment after 2000 h nearly the same production behaviour as at the beginning
      of the fermentation could be observed. This indicated a stable behaviour of the
      population with regard to nikkomycin productivity. The long continuous
      fermentation showed the ability of S. tendae Tu 901/8c to produce nikkomycin at a
      high level for at least 1500 h. In a second continuous culture it was shown that
      the productivity of the nikkomycins and juglomycins decreased and increased,
      respectively, with increasing dilution rate. Comparing batch cultures with
      continuous fermentations, higher juglomycin productivity was found in the latter.
      These facts indicate that the strain responds to complex interacting
      physiological controls, by producing either nikkomycins or juglomycins in a
      higher amount.

PMID- 1368201
TI  - Production of recombinant human glucagon in the form of a fusion protein in
      Escherichia coli; recovery of glucagon by sequence-specific digestion.
AB  - Recombinant human glucagon was successfully produced with a high level of
      expression in Escherichia coli as a fusion protein with human interferon gamma.
      The synthetic gene was designed to release glucagon, which does not contain
      glutamic acid residues, from fusion protein with the Staphylococcus aureus strain
      V8 protease that specifically cleaves the peptide bond on the carboxyl side of
      the glutamic acid residue. The resulting glucagon was purified to homogeneity by
      a combination of C18 reverse-phase HPLC and ion-exchange HPLC. The yield of
      intact glucagon obtained from 11 of culture was approximately 12 mg. The
      structure of recombinant human glucagon was confirmed by HPLC and amino acid
      composition/sequence analyses.

PMID- 1368202
TI  - Promoter constructions for efficient secretion expression in Streptomyces
      lividans.
AB  - Promoters from different Streptomyces genes were cloned in front of the
      Tendamistat gene from S. tendae, in order to study secretion-expression in S.
      lividans using a pIJ702 plasmid vector system. Besides the promoters we cloned a
      transcriptional terminator downstream of the Tendamistat gene to improve
      transcription efficiency. The promoters we selected were: (1) a synthetic
      Escherichia coli-like consensus promoter; (2) the aphI promoter of the neomycin
      resistance gene from S. fradiae; (3) an ermE-up promoter mutant from
      Saccharopolyspora erythraea; (4) the melC promoter of the tyrosinase operon from
      Streptomyces antibioticus. In addition, we tested the thiostrepton-inducible tipA
      promoter from S. lividans in our Tendamistat secretion system. The promoters were
      cloned upstream of the Tendamistat ribosome binding site in order to conserve the
      original translation initiation. The Tendamistat secretion mediated by the
      different promoter constructions above varied dramatically in up to 10 mg/l in
      the case of the synthetic promoter and the aph promoter, and up to 500 mg/l
      mediated by the ermE-up promoter. The melC promoter allowed about 200 mg/l
      Tendamistat secretion and the tipA promoter proved to be inducible from less than
      0.5 mg/l up to 40 mg/l of Tendamistat secretion. Based on the amount of secreted
      Tendamistat and on the analysis of mRNA levels, we conclude that transcriptional
      activity regulates the efficiency of our secretion-expression system.

PMID- 1368203
TI  - Genetic instability of industrial strains of Penicillium chrysogenum.
AB  - It has shown that several characteristics of high-producing industrial strains of
      Penicillium chrysogenum tend to segregate in the course of cultivation (slant-to
      slant transfer). Segregation includes a decrease in the yield of penicillin, mean
      conidial size, mean size of the nuclei, and an increase in the proportion of
      morphologically wild-type colonies. These lower-producing segregants also have a
      higher sensitivity against ultraviolet radiation and, as shown by
      cytofluorometric methods, a lower DNA content in the conidia, a decrease in
      phosphate uptake and in the activity of extracellular alkaline phosphatases
      compared to high-producing strains. Obviously, during mutagenesis/selection
      programmes ploidy mutants have been selected, which entails an increase in the
      number of genes coding enzymes responsible for penicillin biosynthesis. In the
      absence of selection pressure these high-producing strains segregate to lower
      producing strains by chromosome losses in the course of slant-to-slant transfers.

PMID- 1368204
TI  - In vitro mutagenesis of a xylanase from the extreme thermophile Caldocellum
      saccharolyticum.
AB  - Six mutant xylanases were obtained by in vitro mutagenesis of a xylanase gene
      from the extremely thermophilic bacterium Caldocellum saccharolyticum. The
      temperature stability of all enzymes was affected by mutation to various degrees
      and one of the xylanases had an altered temperature optimum. The mutations had no
      effect on the pH optimum. The C. saccharolyticum xylanase showed strong homology
      to several thermophilic and mesophilic xylanases, and comparison of primary
      sequences allowed the localization of probable active sites and residues involved
      in thermostability.

PMID- 1368205
TI  - Fatty acid impurities in alginate influence the phenol tolerance of immobilized
      Escherichia coli.
AB  - A short time after the immobilization of Escherichia coli in calcium alginate
      substantial modifications of the fatty acid patterns of the cells were observed.
      This effect could be related to lipid impurities in the commercial alginate
      product used, which could be taken up, at least in part by the microorganisms.
      The impurities were mainly free fatty acids but sterols were also detected.
      Immobilization of the cells in alginate material extracted by chloroform or
      ethanol decreased the tolerance of the cells to phenol as compared with cells
      immobilized in raw alginate. This effect was diminished if the immobilized cells
      were exogenously supplied with palmitic acid, which is the main constituent of
      the fatty acids extracted from alginate. These results indicate that not only
      fatty acids but also other ingredients of commercial alginate have physiological
      effects on cells entrapped in this gel material.

PMID- 1368206
TI  - Resolution and productivity of conalbumin and lysozyme from fresh egg-white
      loaded at very high flow rate on a 250-mm length CM-HVFM column.
AB  - A 250 x 10 mm I.D. column of CM-HVFM, a novel carboxymethyl ion-exchange matrix,
      has been used as a preparative chromatographic column to separate fresh egg-white
      protein. When loading a diluted egg-white solution at pH 4.8 ovalbumin was not
      adsorbed and lysozyme was preferentially adsorbed compared to the conalbumin. As
      the column loading was increased from 24 to 450 kg m-3 column volume at the
      superficial velocity of 6.12 m h-1, the lysozyme continued to be absorbed
      eventually displacing conalbumin. A maximum lysozyme productivity at 16.7 kg m-3
      h-1 was achieved at the highest loading. For conalbumin a maximum productivity of
      8.8 kg m-3 h-1 occurred at the lower loading of 100 kg m-3. The purities of
      lysozyme and conalbumin were comparable at a column loading of 450 kg m-3 h-1.
      The performance of the column was not degraded, neither was the column blocked or
      channelled despite the high column loading at the high flow-rate.

PMID- 1368207
TI  - Quantitative binding studies of a monoclonal antibody to immobilized protein-A.
AB  - Binding constants and column capacities are important factors for evaluating an
      affinity chromatography system. Scatchard plots based on classical equilibrium
      binding have been used to demonstrate how association constants and column
      capacities can be computed from simple binding experiments and a commercial
      computer program. The analysis has been demonstrated on a monoclonal antibody
      type IgG-1 Kappa against Serratia marcescens nuclease and a commercial protein-A
      column, Prosep-A. Additional analyses were performed with the same antibody and
      other protein-A affinity systems and the different binding constants and column
      capacities obtained confirmed the value of the analysis for evaluating an
      affinity system.

PMID- 1368208
TI  - The partitioning of cholesterol oxidase in Triton X-114-based aqueous two-phase
      systems.
AB  - Cholesterol oxidase from various bacterial sources (membrane-bound and
      extracellular) was studied in Triton X-114R solutions above the cloud point. The
      influence of temperature, salt, enzyme concentration and source, and pH on phase
      equilibrium and enzyme partitioning was investigated in this detergent-based
      aqueous two-phase system. The method combines remarkable recovery (over 70% and
      90% in the detergent-rich phase for the extracellular and membrane-bound forms,
      respectively) and 10 to 20-fold concentration of the enzyme in just one
      purification step. The results from cholesterol oxidase are compared with other
      proteins, both hydrophobic and hydrophilic. The system shows considerable promise
      for selectively partitioning proteins based on their surface hydrophobicity.

PMID- 1368209
TI  - Specific inhibition by cyclodextrins of raw starch digestion by fungal
      glucoamylase.
AB  - alpha-, beta-, and gamma-cyclodextrins (CDs) completely inhibited raw starch
      digestion by glucoamylase I (GA I, MW 90,000) from Aspergillus awamori var.
      kawachi, and inhibited by 85% the raw starch adsorption of GA I at the CD
      concentrations of 1-5 mM. CDs at 1-5 mM did not inhibit gelatinized starch
      hydrolysis by GA I, but at the concentration of 50 mM, they inhibited such
      hydrolysis slightly. GA I was specifically adsorbed onto CD-Sepharose 6B, but
      glucoamylase I' (GA I', MW 73,000), which does not adsorb onto or digest raw
      starch, from the same strain was not adsorbed onto that gel. The adsorption of
      the glucoamylases onto raw starch and CD-Sepharose 6B was correlated to their
      digestion of raw starch. The hydrophobic adsorption of GA I onto CDs and raw
      starch occurred competitively at the Cp region, which is on the C-terminal side
      of Gp-I in the site for raw starch affinity of GA I, and inclusion complexes were
      formed.

PMID- 1368210
TI  - Partial sequence of acid phosphatase-1(1) gene (Aps-1(1)) linked to nematode
      resistance gene (Mi) of tomato.
AB  - A partial amino acid sequence of acid phosphatase-1(1) (apase-1(1)), one of acid
      phosphatase isozymes of tomato, was identified. This information enabled us to
      synthesize degenerated primer pools of oligonucleotides for polymerase chain
      reactions (PCR) using cDNA for poly(A)+ RNA of tomato leaves as a template. As a
      result, a 135-bp, then a 467-bp PCR product were obtained. Nucleotide sequencing
      of these two PCR products gave a total of 522-bp sequence that was identified as
      a part of the Asp-1(1) gene judging from the amino acid sequence deduced from it.
      Using the 135-bp PCR product as a probe, we detected the restriction fragment
      length polymorphism (RFLP) in two different lines of tomato by genomic Southern
      blot analysis. We also did pulsed-field gel electrophoresis (PFGE) and Southern
      blot analysis to search for suitable fragments to clone into a YAC vector. As a
      result, a single band with a size that could be cloned into a YAC vector was
      detected when the genomic DNA was digested with some kinds of restriction
      enzymes.

PMID- 1368211
TI  - Production of human antithrombin-III in a serum-free culture of CHO cells.
AB  - A simple method was developed to establish serum-independent Chinese hamster
      ovary (CHO) cells that grew and secreted high level of human antithrombin-III (AT
      III). First, human AT-III and mouse dihydrofolate reductase (DHFR) cDNAs were
      transfected into DHFR-deficient CHO cells. Transfected cells were treated with
      increasing concentrations of methotrexate (MTX) and clones secreting high levels
      of AT-III (10-20 micrograms/ml/3 day) in a serum-containing medium were obtained.
      Serum-independent clones were derived from the serum-dependent clones by simply
      culturing the cells for a few weeks in a serum-free medium. In a serum-free
      medium the established serum-independent clones grew at normal rate and produced
      almost equivalent amount of AT-III to that of the serum-dependent, parent clones.
      In addition, AT-III from the serum-independent clones has specific activity
      similar to that of plasma-derived AT-III.

PMID- 1368212
TI  - GTP-binding sequences in the gamma subunit of pig liver initiation factor 2.

PMID- 1368213
TI  - Accumulation of grisorixin caused by treating a nigericin-producing strain with a
      P-450 inhibitor.

PMID- 1368214
TI  - Construction of a novel tetracycline resistance gene cassette useful as a marker
      on the Bacillus subtilis chromosome.

PMID- 1368215
TI  - Preparation of amino-terminal half-molecule of ovotransferrin by tryptic
      digestion of intact molecule selectively saturated with Al(III) at the N-lobe.

PMID- 1368216
TI  - NADP-malic enzyme from plants.
AB  - NADP-malic enzyme functions in plant metabolism as a decarboxylase of malate in
      the chloroplast or cytosol. It serves as a source of CO2 for photosynthesis in
      the bundle sheath chloroplasts of C4 plants and in the cytosol of Crassulacean
      acid metabolism plants, and as a source of NADPH and pyruvate in the cytosol of
      various tissues. Mg2+ or Mn2+ is required as a cofactor. The enzyme has a high
      specificity and low Km for NADP+. It exists as a tetramer which may undergo
      changes in oligomerization and exhibit hysteresis. Its kinetic properties vary
      depending on the compartmentation and function of the enzyme. The chloroplast
      form in C4 plants has a high pH optimum (pH 8) under high malate, which favours
      the tetramer, whereas lower pH (pH 7) favours the dimer form. Generally, other
      forms of the enzyme, which are thought to be cytosolic, have lower pH optima than
      the chloroplast enzyme. In a number of cases these forms have been shown to have
      allosteric properties with malate as a substrate. Chemical modifications of the
      plant enzyme suggest sulphydryl, histidine and arginine residues are required for
      catalysis. Primary sequence studies on the chloroplastic enzyme from C4 plants
      show significant similarities to cytosolic NADP-ME in plants and animals,
      including a sequence motif which is indicative of the NADP+ binding site. The
      possible origin of the chloroplast form of the enzyme is discussed.

PMID- 1368217
TI  - Cell wall changes in immature Asparagus stem tissue after excision.
AB  - Cell wall material (CWM) was prepared from sections of fresh and aerobically
      stored asparagus (Asparagus officinalis, L. cv. Connovor Collossus) stems.
      Polymers were solubilized from the CWM by successive extraction with cyclohexane
      trans-1,2-diamine-N N N' N'-tetraacetate (CDTA), Na2CO3 and KOH to leave the
      alpha-cellulose residue which contained a significant amount of cross-linked
      pectic polysaccharides. The polymers were fractionated by anion-exchange
      chromatography and selected fractions were subjected to methylation analysis. The
      storage-related decrease in (1-4)-linked Galp was detected in all the fractions
      rich in pectic polysaccharides, particularly in the CDTA, Na2CO3, 0.5 M KOH
      fractions and alpha-cellulose residue. A smaller decrease in Araf was also
      observed. This was mainly due to a decrease in (1-5)-linked Araf in the Na2CO3-1
      soluble polymers, and terminal Araf in the alpha-cellulose residue. There was
      evidence for the occurrence of significant amounts of complexes containing pectic
      polysaccharides and xylans having a relatively low degree of polymerization in
      the dilute alkali-soluble polymers, and some of these contained phenolic
      compounds; the storage-induced increase in (1-4)-linked Xylp was confined to
      these polymers. Interestingly, no free acidic xylans could be detected in the 1 M
      and 4 M KOH-soluble polymers; instead, the bulk of the hemicellulosic
      polysaccharides appeared to be mixtures of xyloglucans and xylans in which the
      ratio of xyloglucan to xylan increased with increasing strength of alkali used
      for extraction of the polymers. The non-degradative extraction and fractionation
      procedures revealed heterogeneity in pectic polysaccharides, pectic
      polysaccharide-xylan complexes and xyloglucans in close association with xylans.
      The possible relationship between pectic polysaccharide-xylan-phenolic complexes
      and the onset of lignification in maturing tissues is discussed.

PMID- 1368218
TI  - Antioxidant activity of flavonoids from Sideritis javalambrensis.
AB  - Five flavonoid glycosides, 4'-O-methylisoscutellarein 7-O-[6"'
      acetylallopyranosyl(1----2)glucopyranoside], 4'-O-methylisoscutellarein 7-O
      allopyranosyl(1----2)glucopyranoside, 3'-hydroxy-4'-O-methylisoscutellarein 7-O
      [6"'-acetylallopyranosyl(1----2) glucopyranoside], and hypolaetin-8-glucoside
      have been isolated from Sideritis javalambrensis aerial parts and identified by
      standard methods. These glycosides have been tested for their antioxidant
      properties alongside other 7,8-substituted flavonoids using FeSO4/cysteine
      induced microsomal lipid peroxidation. Superoxide scavenging activity was
      assessed in the nitroblue tetrazolium test. Among this series of flavonoids,
      hypolaetin-8-glucoside is the most potent inhibitor of nonenzymic lipid
      peroxidation. The antiperoxidative activity of these flavonoids may be related to
      their superoxide scavenging ability.

PMID- 1368219
TI  - Triterpenoid saponins from Argania spinosa.
AB  - Five new oleanane saponins named arganine A, B, D, E and F and two known
      saponins: arganine C and mi-saponin A were isolated from the kernel of Argania
      spinosa. The structures of these saponins were elucidated by using 1H NMR, 1H-1H
      COSY NMR, 13C NMR, FAB mass spectrometry and chemical evidence.

PMID- 1368220
TI  - Steroidal constituents from Amalocalyx yunnanesis.

PMID- 1368221
TI  - Determination of the reactivities and cross-reactivities of monoclonal antibodies
      against staphylococcal enterotoxin A by indirect ELISA and immunoblot including a
      semiautomated electrophoresis system.
AB  - Eight murine monoclonal antibodies (Mabs) to staphylococcal enterotoxin A (SEA)
      were produced using standard hybridoma techniques. We studied reactivities and
      cross-reactivities by indirect ELISA and immunoblotting. Two of these Mabs (A5
      and A7) reacted with five serovars (A-E) of SE in both systems. Only Mab A1
      reacted specifically with the homologous toxin, while four Mabs reacted with SEA
      and SEE. Mabs A5 and A7 could be used to detect all five serovars of SEs in a
      single assay.

PMID- 1368222
TI  - Genes in a bottle.

PMID- 1368223
TI  - PCR: catching the next wave.

PMID- 1368224
TI  - Hypertexting through the regulations.

PMID- 1368225
TI  - bST & the EEC: politics vs. science.

PMID- 1368226
TI  - Signal transduction: untangling its golden promise.

PMID- 1368227
TI  - Rational immunotherapy with interleukin 2.
AB  - Interleukin 2 (IL-2), a T lymphocyte product released upon antigen stimulation,
      has been used for cancer therapy in high doses for more than five years. More
      recently, its potential as a stimulant of cell-mediated immunity in infectious
      diseases, particularly those caused by intracellular microbes, has become
      appreciated. Drawing on the extensive information available as to the structure,
      cellular and molecular effects of IL-2, this review focuses on its use in
      patients with lepromatous leprosy and AIDS in low, physiologic doses. The data
      indicate that IL-2 is effective in stimulating cell-mediated immunity without
      systemic toxicity.

PMID- 1368228
TI  - High level Escherichia coli expression and production of a bivalent humanized
      antibody fragment.
AB  - Many clinical uses of antibodies will require large quantities of fragments which
      are bivalent and humanized. We therefore attempted to generate humanized F(ab')2
      fragments by secretion from E. coli. Titers of 1-2 g l-1 of soluble and
      functional Fab' fragments have been routinely achieved as judged by antigen
      binding ELISA. Surprisingly, this high expression level of Fab' in the
      periplasmic space of E. coli does not drive dimerization. However, we have
      developed a protocol to directly and efficiently recover Fab' with the single
      hinge cysteine in the free thiol state, allowing F(ab')2 formation by chemically
      directed coupling in vitro. The E. coli derived humanized F(ab')2 fragment is
      indistinguishable from F(ab')2 derived from limited proteolysis of intact
      antibody in its binding affinity for the antigen, p185HER2, and anti
      proliferative activity against the human breast tumor cell line, SK-BR-3, which
      over-expresses p185HER2. This system makes E. coli expression of bivalent
      antibody fragments for human therapy (or other uses) practical.

PMID- 1368229
TI  - Growth enhancement in transgenic Atlantic salmon by the use of an "all fish"
      chimeric growth hormone gene construct.
AB  - We have developed an "all fish" growth hormone (GH) chimeric gene construct by
      using an antifreeze protein gene (AFP) promoter from ocean pout linked to a
      chinook salmon GH cDNA clone. After microinjection into fertilized, nonactivated
      Atlantic salmon eggs via the micropyle, transgenic Atlantic salmon were
      generated. The presence of the transgene was detected by polymerase chain
      reaction (PCR) using specific oligonucleotide primers. A number of these
      transgenic fish showed dramatic increases in their growth rate. At one year old,
      the average increase of the transgenic fish was 2 to 6 fold and the largest
      transgenic fish was 13 times that of the average non-transgenic control.

PMID- 1368230
TI  - Expression of cloned homologous fermentative genes in Clostridium acetobutylicum
      ATCC 824.
AB  - We have previously cloned the acetone-formation pathway gene, encoding
      acetoacetate decarboxylase (adc), and butyrate-formation pathway gene, encoding
      phosphotransbutyrylase (ptb), of Clostridium acetobutylicum ATCC 824 in
      Escherichia coli. Here we report their subcloning in Bacillus subtilis and
      transfer to strain ATCC 824 via electrotransformation, where the corresponding
      enzyme activities were expressed at elevated levels, using pFNK1, a new B.
      subtilis/C. acetobutylicum shuttle vector. Plasmid pFNK1 was used because shuttle
      vectors that function in E. coli were unable to electrotransform ATCC 824 unless
      they became deleted in the E. coli-plasmid regions. The difficulties with shuttle
      vectors that function in E. coli are probably due to the presence of a
      restriction endonuclease in ATCC 824. This endonuclease recognizes the sequence
      5'-GCNGC-3', which is prevalent in E. coli plasmids but occurs infrequently in
      pFNK1 and C. acetobutylicum genes. Cloning of genes in C. acetobutylicum is
      critical for redirecting the cellular metabolism (metabolic engineering) as well
      as for genetic studies of this industrial organism.

PMID- 1368231
TI  - Shedding light on peptide synthesis.

PMID- 1368232
TI  - Biopharmaceuticals and conventional drugs: clinical success rates.

PMID- 1368234
TI  - A novel strategy for secreting proteins: use of phosphatidylinositol-glycan
      specific phospholipase D to release chimeric phosphatidylinositol-glycan anchored
      proteins.
AB  - Phosphatidylinositol-glycan-specific phospholipase D (PI-G PLD) specifically
      hydrolyzes the inositol-phosphate linkage in phosphatidylinositol-glycan (PI-G)
      anchored proteins. We recently deduced the primary structure of this enzyme and
      demonstrated specific enzymatic activity in transfected cells. Co-transfection of
      PI-G PLD with a natural PI-G anchored protein resulted in the secretion of the PI
      G anchored protein via a PI-G PLD specific mechanism. We have taken advantage of
      these observations to develop an alternative system that may be useful for
      expressing and secreting proteins not amenable to secretion by conventional
      methods. Chimeric PI-G anchored proteins were constructed by transferring the
      COOH-terminal signal peptide for PI-G anchor attachment from placental alkaline
      phosphatase or from the low affinity IgG receptor, FcGRIIIB, to proteins that are
      not normally PI-G anchored. This process facilitates the cell surface expression
      of several proteins including the high affinity IgE receptor alpha subunit, FcERI
      alpha, which otherwise requires at least one other subunit for surface
      expression. Co-expression of these chimeric PI-G anchored proteins with PI-G PLD
      resulted in their secretion via a PI-G PLD specific mechanism.

PMID- 1368233
TI  - Modifying the mouse: design and desire.
AB  - Genetic modification of endogenous genes in mice has become possible by applying
      gene targeting techniques to embryonic stem (ES) cells and using specific clones
      of cells to generate mice. Despite the experimental opportunities offered by the
      creation of organisms with specific genetic changes, there are considerable
      technical obstacles which can confound the routine implementation of this
      technology. This review addresses some recent advances in the ability to
      construct mice with a variety of genetic modifications. These include an
      increased understanding of the basic cell biology and in vitro growth
      characteristics of ES cells, which has facilitated germ line transmission of
      manipulated clones on a routine basis. The techniques that are used to isolate
      "targeted" clones of ES cells have been summarized, and the current status of
      strategies which have been successfully used to make very specific modifications
      of the genome are discussed.

PMID- 1368235
TI  - Production of functional human hemoglobin in transgenic swine.
AB  - A construct containing the locus control region (LCR) from the human beta globin
      locus together with two copies of the human alpha 1 gene and a single copy of the
      human beta A gene was used to obtain three transgenic pigs. The transgenic pigs
      are healthy, not anemic, and grow at a rate comparable to non-transgenic
      littermates. All animals expressed the human genes. However, alpha globin was
      consistently expressed at higher levels than beta globin. Isolation of the human
      hemoglobin from both porcine hemoglobin and other non-hemoglobin proteins was
      accomplished by ion exchange chromatography. The purified porcine derived human
      hemoglobin exhibited an oxygen affinity similar to that of human derived human
      hemoglobin.

PMID- 1368237
TI  - Application of a recycle dialysis system in a reversed micellar reactor.
AB  - A recycle dialysis stirred cell has been successfully used for integrating the
      reaction and product recovery of the lipase-catalyzed hydrolysis of olive oil in
      bis(2-ethylhexyl) sodium sulfosuccinate (AOT)-iso-octane reversed micelles. The
      resistance of membrane to reversed micelles was monitored by the water content
      and found to be 95.9% rejection after 24 h and 93.4% rejection after 48 h. The
      resistance of the membrane to free surfactants, by monitoring the UV absorption,
      was found to be 98.5% rejection after 10 h and 97.3% rejection after 24 h.
      Mathematical formulations involving the enzymatic reaction coupled with mass
      transfer were developed for predicting the performance of a membrane reactor.
      Theoretical predictions in terms of time course of oleic acid concentrations were
      found to be in agreement with the experimental results.

PMID- 1368236
TI  - A sensitive model system for in vivo monitoring of baculovirus gene expression in
      single infected insect cells.
AB  - We have developed a fast and sensitive system for the in vivo analysis of gene
      expression in baculovirus infected lepidopteran insect cells. A recombinant
      baculovirus containing a luciferase gene from the click beetle, Pyrophorus
      plagiophthalamus, under transcriptional regulation of the polyhedrin gene
      promoter of Autographa californica nuclear polyhedrosis virus (AcNPV) was used to
      infect a Spodoptera frugiperda cell line. Recombinant luciferase could be
      monitored by luminometry in real-time without disruption of the infected cells,
      allowing detection of synthesis as early as one hour after infection. The range
      of luminescence measurements was normally over four orders of magnitude, and the
      kinetics of luciferase synthesis and the levels of light produced in vivo closely
      correlated with the expression of polyhedrin in AcNPV infected cells when
      analyzed by SDS-PAGE. Additionally, single infected cells could be identified by
      CCD image analysis and flow cytometry.

PMID- 1368238
TI  - Extended summaries. SCI Biotechnology Group meeting: risk assessment in
      biotechnology. London, June 20, 1991. Abstracts.

PMID- 1368239
TI  - The influence of preculture on the process performance of penicillin V production
      in a 100-l air-lift tower loop reactor.
AB  - The influence of stirrer speed in the third preculture on the performance of
      penicillin V production by Penicillium chrysogenum in complex medium in a 100-l
      air-lift tower loop reactor was investigated. The process performance in the main
      culture was improved by increasing the stirrer speed from 500 to 750 rpm: the
      pellet size was reduced to half, the cell growth was influenced only slightly,
      but the production phase was extended considerably, and the final penicillin
      concentration was increased from 5.1 g l-1 to 10.4 g l-1.

PMID- 1368240
TI  - Extracellular alpha-amylase from Streptomyces rimosus.
AB  - A purification procedure for an extracellular alpha-amylase from Streptomyces
      rimosus, oxytetracycline-producing strain, is described. The enzyme obtained was
      shown to be an acidic (pI 4.75) monomer with a relative molecular mass (M(r)) of
      43,000, containing three cysteines involved in the catalytic activity of the
      enzyme. Its amino-terminal part has 57-67% homology with amylases from other
      Streptomyces species. S. rimosus alpha-amylase is sensitive to higher
      temperatures, and partially stabilized by Ca2+ ions. It hydrolyses starch
      (optimum at pH 5.0-6.0) in an endohydrolase manner giving rise to maltotriose,
      maltotetraose and higher oligosaccharides. Starch granules, except those from
      rice, were not significantly affected by the isolated alpha-amylase.

PMID- 1368241
TI  - High-level expression and purification of mature HIV-1 protease in Escherichia
      coli under control of the araBAD promoter.
AB  - A 1.3-kb segment of Escherichia coli DNA containing the regulatory gene, araC,
      and the promoter of the araBAD operon was amplified by the polymerase chain
      reaction (PCR) and cloned into pUC18, resulting in plasmid pKB130 that produced
      the alpha fragment of beta-galactosidase upon addition of L-arabinose (L-ara). A
      synthetic gene for human immunodeficiency virus (HIV)-1 preprotease was placed
      downstream of the ara-BAD promoter in pKB130 to create a translational fusion
      inducible by addition of L-ara. The fusion protein correctly autoprocessed in
      vivo to yield a mature 99-amino-acid HIV-1 protease, which was found
      predominantly in inclusion bodies. This material could be refolded to an active
      form, which was purified to homogeneity. A small fraction of the protease was
      expressed in vivo as a soluble active form, which allowed the monitoring of
      expression during fermentation by a rapid and simple whole cell assay employing
      an HIV-1 protease-specific fluorogenic substrate.

PMID- 1368243
TI  - Growth and death behaviour of anchorage-independent animal cells immobilized
      within porous support matrices.
AB  - Growth and death of anchorage-independent animal cells entrapped within porous
      biomass support particles (BSPs) in static or shake-flask cultures were evaluated
      by comparison of enzyme activity with non-immobilized cells grown under static
      culture using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)
      assay and release of lactate dehydrogenase into the culture medium. Mouse myeloma
      MPC-11 (ATCC CCL 167) cells inoculated within porous polyvinyl formal resin BSPs
      (3 x 3 x 3 or 2 x 2 x 2 mm; mean pore diameter, 60 microns) grew exponentially at
      a specific growth rate comparable to that of non-immobilized cells in the initial
      period of incubation. Entrapped cells then reached the stationary phase with a
      cell density over 10(7) cells/cm3 BSP. The death rate of entrapped cells
      increased in response to the rise in viable cell density in the BSPs. Observation
      of viable cell distribution within the BSPs using MTT staining indicated that the
      cells concentrated within a thin outer shell of the BSPs with time. After the
      immobilized cells reached the stationary phase, penetration of cells into the
      outer shell ceased and heterogeneous distribution of cell density occurred in the
      viable cell layer in the shake-flask culture.

PMID- 1368242
TI  - Transfer of genes for utilization of starch (sta2) and melibiose (mel) to
      industrial strains of Saccharomyces cerevisiae by single-chromosome transfer,
      using a kar1 mutant as vector.
AB  - A method has been developed for the transfer of genes from other yeast strains
      and species to industrial yeast strains, using a haploid, kar1-1 mutant strain of
      Saccharomyces cerevisiae as a vector. The sta2 gene, conferring the ability to
      metabolize starch was transferred from an auxotrophic haploid strain of S.
      cerevisiae (S. diastaticus) and the melibiose-metabolism (mel) gene(s), from S.
      kluyveri, to the kar1-1 mutant [K5-5A; (alpha ade2 his4 can1 gal) by normal
      mating and protoplast fusion. From this strain, the genes were transferred to
      baker's yeast and brewing yeast strains, which did not utilize starch, and to
      baker's yeast strains, which did not utilize melibiose, by protoplast fusion,
      spore-cell pairing, or rare-mating. Strains that utilized starch or melibiose
      were obtained by all three methods. Pulsed-field gel electrophoresis preparations
      showed little change in the mobility of the chromosomes of the hybrids. The most
      probable explanation for the results obtained is that single chromosomes were
      transferred, first, from the donor strains to the kar1-1 haploid mutant strain,
      and then from the kar1-1 vector to the recipient industrial strain of S.
      cerevisiae. The transfer of the genes is probably accomplished through formation
      of disomic strains and then, in the case of the hybrids that metabolize starch,
      by integration of the sta2 gene into the genome of the industrial yeast strains.

PMID- 1368244
TI  - Degradation of phenol and phenolic compounds by Pseudomonas putida EKII.
AB  - The phenol-degrading strain Pseudomonas putida EKII was isolated from a soil
      enrichment culture and utilized phenol up to 10.6 mM (1.0 g.l-1) as the sole
      source of carbon and energy. Furthermore, cresols, chlorophenols, 3,4
      dimethylphenol, and 4-chloro-m-cresol were metabolized as sole substrates by
      phenol-grown resting cells of strain EKII. Under conditions of cell growth,
      degradation of these xenobiotics was achieved only in co-metabolism with phenol.
      Phenol hydroxylase activity was detectable in whole cells but not in cell-free
      extracts. The specificity of the hydroxylating enzyme was found during
      transformation of cresols and chlorophenols: ortho- and meta-substituted phenols
      were degraded via 3-substituted catechols, while degradation of para-substituted
      phenols proceeded via 4-substituted catechols. In cell-free extracts of phenol
      grown cells a high level of catechol 2,3-dioxygenase as well as smaller amounts
      of 2-hydroxymuconic semialdehyde hydrolyase and catechol 1,2-dioxygenase were
      detected. The ring-cleaving enzymes were characterized after partial purification
      by DEAE-cellulose chromatography.

PMID- 1368245
TI  - Protein secretion in gram-positive bacteria.
AB  - Gram-positive bacteria often secrete large amounts of proteins into the
      surrounding medium. This feature makes them attractive as hosts for the
      industrial production of extracellular enzymes. Compared to Escherichia coli,
      relatively little is known about the mechanism of protein secretion in these
      organisms. However, the recent identification of Bacillus subtilis genes whose
      gene products are highly homologous to some of the Sec (secretion) proteins of E.
      coli strongly suggests that important principles of protein translocation across
      the plasma membrane might be highly conserved. In contrast, the steps following
      the actual translocation event might be different in Gram-positive and Gram
      negative bacteria. The scope of this review is to outline the recent progress
      that has been made in the elucidation of the secretion pathway in Gram-positive
      bacteria and to discuss potential applications in strain improvement for the
      industrial production of extracellular proteins.

PMID- 1368246
TI  - Optimization of a cultivation process for recombinant protein production by
      Escherichia coli.
AB  - A single-stage fed-batch bioprocess for the production of a recombinant protein
      beta-galactosidase, by E. coli has been developed. The XL1-blue strain of E. coli
      which harbors a multi-number foreign plasmid PT was cultured in a reformulated
      medium. Critical medium components were selected and their respective
      concentrations were optimized with the Orthogonal Table method. An exponential
      substrate feeding schedule was used to maintain optimum conditions. Inhibition of
      growth and protein expression caused by excessive concentrations of glucose and
      acetate was investigated and subsequently minimized with an incremental nutrient
      feeding schedule which limited the specific growth rate of a culture. The program
      necessary to facilitate the control of substrate addition is fully described.
      This program has been used with a 2.5 l bioreactor and a commercially available
      software package for optimization without on-line or off-line measurement of
      optical density (OD), CO2, glucose or acetate. The optimized fed-batch process
      limited the acetate concentration to less than 20 mM; maintained an exponential
      growth phase for 50 h; and produced a cell density of 51 g l-1 dry cell weight
      (DCW) or 154 OD600 with a beta-galactosidase activity of 990 U ml-1.

PMID- 1368248
TI  - On-line biomass monitoring by capacitance measurement.
AB  - An in-situ, steam-sterilizable capacitance probe was used to follow the biomass
      concentration on-line, in bioreactors from 20 to 2000 l total volume. Microbial
      cultures of Saccharomyces cerevisiae, Pichia pastoris and Streptomyces virginiae
      were grown in batch and fed-batch culture in both defined and complex media in
      order to demonstrate the wide dynamic operating range of the instrument. A linear
      correlation was found between the on-line capacitance measurement and the off
      line measurements (optical density, OD620; packed mycelial volume, PMV; biomass
      concentration X, and colony forming units, CFU ml-1) for biomass concentrations
      (dry cell weight) up to 30 g l-1 (St. virginiae), 106 g l-1 (S. cerevisiae) and
      89 g l-1 (P. pastoris). The on-line capacitance measurement was slightly
      influenced by variations in agitation speed and strong extraneous radio
      frequencies. A specific capacitance constant (Cs) was defined for all microbial
      cells which was dependent on cell viability and cell size. The Cs was easy to
      calculate using the on-line capacitance measurement and an off-line estimation of
      biomass concentration. The Biomass Monitor proved suitable for precise on-line
      monitoring of both homogeneous (uni-cellular) and heterogeneous (mycelial)
      cultures in bioreactors.

PMID- 1368247
TI  - Production of recombinant human interferon-alpha 1 by Escherichia coli using a
      computer-controlled cultivation process.
AB  - Genetically engineered E. coli K12 BMH-71-18 with plasmid PBV-867 was used for
      constitutive expression of human interferon-alpha 1 (IFN) with a defined medium.
      A manual, time-based, fed-batch cultivation process produced a cell density of
      26.3 g l-1 (OD550 89), an IFN activity of 1.55 x 10(8) IU l-1 and a specific IFN
      productivity of 0.65 x 10(6) IU g-1. An analysis was conducted to characterize
      the problems involved in the high density microbial processes of recombinant
      protein production. The strategy suggested by the analysis is to establish a
      nutrient feeding profile that improves both the plasmid stability and the overall
      productivity of IFN. The nutrient feeding procedure developed here was based on
      the growth dynamics and a glucose consumption model. By using this procedure to
      continuously supply nutrients during cultivations, cell density reached 58 to 80
      g l-1 and the specific IFN productivities of these runs were increased over that
      of the manual process. Nutrient feeding rates were found to affect the specific
      IFN productivity substantially. The optimized process achieved an IFN activity of
      1.26 x 10(9) IU l-1, a cell density of 58 g l-1 and a specific IFN productivity
      of 2.2 x 10(7) IU g-1. More significantly, the overall productivity IU l-1 h-1 of
      the optimized, computer-controlled cultivation process was increased 12.9-fold
      over that of the manual cultivation process.

PMID- 1368249
TI  - Influence of medium composition on the cephalosporin C production with a highly
      productive strain Cephalosporium acremonium.
AB  - Cephalosporin production by a highly productive Cephalosporium acremonium strain
      was carried out and optimized by fed-batch operation in a 40 l stirred tank
      reactor using a complex medium containing 30-120 g l-1 peanut flour. The
      concentrations of cephalosporin C (CPC) and its precursors: penicillin N (PEN N),
      deacetoxy cephalosporin C (DAOC), and deacetyl cephalosporin C (DAC) were
      monitored with an on-line HPLC. The concentrations of amino acids valine (VAL),
      cysteine (CYS), alpha-amino adipic acid (alpha-AAA), the dipeptide alpha-amino
      adipyl-cysteine (AC), and the tripeptide alpha-amino-adipyl-cysteinyl-valine
      (ACV), were determined off-line by HPLC. The RNA content and dry weight of the
      sediment as well as the oxygen transfer rate (OTR) and the CO2 production rate
      (CPR) were used to calculate the cell mass concentration (X). The influences of
      peanut flour (PF) and the on-line monitored and controlled medium components:
      glucose (GLU), phosphate, methionine (MET) as well as the dissolved oxygen (DOC)
      on the cell growth, the product formation, and the pathway of cephalosporin C
      biosynthesis were investigated and evaluated. When the glucose fed-batch cycle
      was optimized and oxygen transfer limitation was avoided (DOC greater than 20% of
      the saturation value), high process performance (103.5 g l-1 X, 11.84 g l-1 CPC,
      a maximum CPC productivity of 118 mg l-1 h-1, and the whole concentration of the
      beta-lactam antibiotics CPC, DAC, DAOC, PEN N 17.34 g l-1) was achieved by using
      100 g l-1 PF in the medium with the optimum concentration of phosphate (260-270
      mg l-1) and a low glucose concentration (less than 0.5 g l-1). The cultivations
      with different medium concentrations demonstrated that the product formation was
      directly proportional to the cell mass concentration. On the average, the cell
      mass-based yield coefficient of CPC: YCPC/X amounted to 0.115 g CPC per g cell
      mass.

PMID- 1368250
TI  - Maturation of an NH2-terminally extended thermostable alpha-amylase in Bacillus
      subtilis: a possible mechanism examined by in vitro experiments.
AB  - An artificially inserted extra peptide (21 amino acid peptide) between the B.
      subtilis alpha-amylase signal peptide and the mature thermostable alpha-amylase
      was completely cleaved by B. subtilis alkaline protease in vitro. The cleavage to
      form a mature enzyme was observed between pH 7.5 and 10, but not between pH 6.0
      and 6.5, although a similar protease activity toward Azocall was observed between
      pH 6.0 and 7.5. To analyze the effects of pH on the cleavage, CD spectra at pH 6,
      8, and 11 of the NH2-terminally extended thermostable alpha-amylase were analyzed
      and the results were compared with those of the mature form of the alpha-amylase.
      It is suggested that the cleavage of the NH2-terminally extended peptide is
      controlled by the secondary and tertiary structure of the precursor enzyme.
      Similar cleavage of different NH2-terminally extended peptides by the alkaline
      protease was also found in other hybrid thermostable alpha-amylases obtained.

PMID- 1368251
TI  - Nucleotide sequence of the gene for an alkaline endoglucanase from an
      alkalophilic Bacillus and its expression in Escherichia coli and Bacillus
      subtilis.
AB  - The gene for an alkaline endoglucanase from the alkalophilic Bacillus sp. KSM-64
      was cloned into the HindIII site of pBR322 and expressed in Escherichia coli
      HB101. The nucleotide sequence of a 4.1-kb region of the HindIII insert had two
      open reading frames, ORF-1 and ORF-2. The protein deduced from ORF-1 was composed
      of 244 amino acids with an M(r) of 27,865. Subcloning analysis proved that the
      alkaline endoglucanase was encoded by ORF-2 (822 amino acids with an M(r) of
      91,040). Upstream from ORF-2, there were three consensus like sequences of the
      sigma A-type promoter of Bacillus subtilis, a putative Shine-Dalgarno sequence
      (AGGAGGT), and a catabolite repression operator-like sequence (TGTAAGCGGTTAACC).
      The HindIII insert was subcloned into a shuttle vector, pHY300PLK, and the
      encoded alkaline endoglucanase gene was highly expressed both in E. coli and B.
      subtilis. One of the three promoter-like sequences in ORF-2 could be suitable for
      high levels of enzyme expression in both host organisms.

PMID- 1368252
TI  - Glycinin A4A5 subunit digesting protease in soybean seeds.
AB  - Endopeptidase was partially purified from the globulin fraction of 4-hr-imbibed
      soybean seeds. The protease fraction obtained had proteolytic activity on the
      glycinin A4A5 subunit at both pH 4 and 8. A suitable peptidic substrate for the
      endopeptidase was isolated from the tryptic digest of the carboxymethylated A4A5
      subunit. Using the tryptic peptide of glycinin A5 subunit, a simple assay system
      for the soybean endopeptidase activity has been established. The activity was
      significantly inhibited by phenylmethylsulfonyl fluoride, indicating the
      endopeptidase is a serine protease.

PMID- 1368253
TI  - Construction of an alpha-amylase/glucoamylase fusion gene and its expression in
      Saccharomyces cerevisiae.
AB  - A fusion gene which encoded a polypeptide comprised of 1116 amino acids was
      constructed using the alpha-amylase and glucoamylase cDNAs of Aspergillus
      shirousamii. When the fusion gene was expressed in Saccharomyces cerevisiae using
      a yeast expression plasmid under the control of the yeast ADH1 promoter, a
      bifunctional fusion protein (145 kDa) having both alpha-amylase and glucoamylase
      activities was secreted into the culture medium. The fusion protein had higher
      raw-starch-digesting activity than those of the original alpha-amylase and
      glucoamylase, and adsorbed onto raw starch like the glucoamylase. It was
      suggested that the characteristics are a result of the raw-starch-affinity site
      in the glucoamylase domain of the fusion protein.

PMID- 1368254
TI  - Cloning and sequencing of the xynA gene encoding xylanase A of Aspergillus
      kawachii.
AB  - We have cloned the xynA gene coding for xylanase A, a major component of the
      xylanase family, from Aspergillus kawachii. The cDNA was isolated from an A.
      kawachii cDNA library by immunoscreening using antibody raised against the
      purified xylanase A protein. Nucleotide sequence analysis of the cDNA showed a
      981-bp open reading frame that encoded a protein of 327 amino acid residues. The
      signal peptide was composed of 25 amino acid residues and the N-terminus of the
      mature protein was pyroglutamic acid. The transformed yeast with a cloned cDNA
      produced xylanase. The genomic DNA was arranged as ten exons and nine introns.

PMID- 1368255
TI  - Inhibition of prolyl endopeptidase by synthetic beta-casein peptides and their
      derivatives with a C-terminal prolinol or prolinal.

PMID- 1368256
TI  - Immunoadsorption: strategies for antigen elution and production of reusable
      adsorbents.
AB  - Immunoadsorption is a powerful and generalizable method for protein purification
      that exploits the fine specificity of antigen-antibody interactions. In spite of
      its potential utility, the more widespread process scale use of immunoadsorption
      has been limited by the high cost of the antibody and the lack of gentle elution
      schemes that completely preserve the activity of both the immunoadsorbent and the
      eluted product. In this report, we review common chemical elution strategies such
      as pH, ionic strength, chaotropic salts, denaturants, and organic solvents as
      well as physical techniques such as pressure, electrokinetics, and temperature.
      In general, selection of elution strategies has largely been an empirical art,
      balancing stability of the immunoadsorbent and the eluted product and efficiency.
      The limitations of the available choices demonstrate that more attention must be
      placed on the antibody. Techniques which assist in the identification or creation
      of new antibodies with improved binding properties and resistance to degradation,
      e.g., screening and/or rational protein engineering, are also discussed.

PMID- 1368257
TI  - Kinetics of adsorption of globular proteins at an air-water interface.
AB  - Adsorption of globular proteins at an air-water interface from an infinite
      stagnant medium was modeled as one-dimensional diffusion in a potential field.
      The interaction potential experienced by an adsorbing molecule consisted of
      contributions from electrostatic interactions, work done against the surface
      pressure to clear area at the interface in order to anchor the adsorbed segments,
      and the change in the free energy due to exposure of penetrated surface
      hydrophobic functional groups to air. The assumption of irreversible adsorption
      is employed in the present analysis. The energy barrier to adsorption, present at
      sufficiently large surface pressures, was found to be higher for smaller surface
      hydrophobicities, larger surface pressures, larger size molecules, and oblate
      orientation of an ellipsoidal molecule. Consequently, more adsorption occurred at
      larger surface hydrophobicities, smaller size molecules, and for prolate
      orientation of ellipsoidal molecules. The subphase concentration has been shown
      to be zero at short times, increasing with time at larger times, and eventually
      becoming close to the bulk concentration as a result of increasing energy barrier
      to adsorption. The predicted evolution of surface concentration with time for
      adsorption of lysozyme at an air-water interface agreed well with the
      experimental data of Graham and Phillips (1979a).

PMID- 1368258
TI  - Physiological and genetic strategies for enhanced subtilisin production by
      Bacillus subtilis.
AB  - Defined minimal media conditions were used to assess and subsequently enhance the
      production of subtilisin by genetically characterized Bacillus subtilis strains.
      Subtilisin production was initiated by the exhaustion or limitation of ammonium
      in batch and fed-batch cultures. Expression of the subtilisin gene (aprE) was
      monitored with a chromosomal aprE::lacZ gene fusion. The beta-galactosidase
      production driven by this fusion reflected subtilisin accumulation in the culture
      medium. Subtilisin gene expression was temporally extended in sporulation
      deficient strains (spoIIG), relative to co-genic sporogenous strains, resulting
      in enhanced subtilisin production. Ammonium exhaustion not only triggered
      subtilisin production in asporogenous spoIIG mutants but also shifted carbon
      metabolism from acetate production to acetate uptake and resulted in the
      formation of multiple septa in a significant fraction of the cell population. Fed
      batch culture techniques, employing the spoIIG strain, were investigated as a
      means to further extend subtilisin production. The constant provision of ammonium
      resulted in linear growth, with doubling times of 11 and 36 h in each of two
      independent experiments. At the lower growth rate, the responses elicited
      (subtilisin production, glucose metabolism, and morphological changes) during the
      feeding regime closely approximated the ammonium starvation response, while at
      the higher growth rate a partial starvation response was observed.

PMID- 1368259
TI  - A stable long-term hepatocyte culture system for studies of physiologic
      processes: cytokine stimulation of the acute phase response in rat and human
      hepatocytes.
AB  - Prior studies on the in vitro hepatic acute phase response have involved either
      hepatoma cell lines or conventional short-term cultures of primary hepatocytes.
      No data are available on the response of primary hepatocytes in stable long-term
      culture systems. In this study, the acute phase response of rat and human
      hepatocytes in a new long-term culture system was examined in response to
      interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and tumor necrosis factor
      alpha (TNF-alpha). The cultured cells were sandwiched between two layers of
      collagen in a (double-gel) configuration which has been shown to preserve both
      hepatocyte function and morphology over prolonged periods of time. The stability
      of this culture configuration enabled us to investigate, for the first time, the
      temporal aspects of the response in addition to the effects of the mediators on
      protein secretion. Exposure of rat hepatocytes to IL-6 after culture for 16 days
      resulted in a 2-fold reduction of albumin secretion and a 15-fold increase in the
      secretion rates of fibrinogen and alpha 2-macroglobulin. In all instances, the
      peak response occurred at 48 h after IL-6 exposure, and all protein secretion
      rates returned to pretreatment values within 5 days posttreatment. Changes in the
      mRNA levels of these proteins in response to IL-6 corresponded with those changes
      seen with the secreted products, indicating pretranslational regulation.
      Administration of IL-1 beta to rat hepatocyte produced a similar decline of
      albumin secretion and a 5-fold increase of fibrinogen secretion, whereas alpha 2
      macroglobulin secretion remained undisturbed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1368261
TI  - Sequence--so what?

PMID- 1368260
TI  - Oxygen mass transfer enhancement via fermentor headspace pressurization.
AB  - Bioreactor headspace pressurization represents an excellent means of enhancing
      oxygen mass transfer to a culture. This method is particularly effective in
      situations where stirring or vigorous aeration is difficult. Because it in itself
      introduces no undesirable hydrodynamic force, the proposed method is also
      attractive for cells susceptible to agitation and sparging. Experiments were
      first conducted in an ideal fermentor by sparging air into a sulfite solution
      free from extraneous microbial effects. An increased oxygen mass transfer rate
      resulting from pressurization led to a superior cell growth rate and a higher
      maximum cell density in both of the microbial systems studied: a bacterial
      (Escherichia coli) culture up to 2.72 bar and a fragile algal (Ochromonas
      malhamensis) culture with pressure programming. Applying pressurization increased
      the maximum dry cell weight from 1.47 g/L to 1.77 g/L in the E. coli culture and
      increased the maximum viable cell density from 4 x 10(7) cells/mL to 10(8)
      cells/mL in the algal culture. An additional advantage is that formation of
      undesirable products under oxygen limitation, e.g., acetic acid in the E. coli
      culture, can be suppressed. A significant (over 250%) improvement in the oxygen
      transfer rate can be achieved with existing fermentors with little modification
      as they are already designed to withstand reasonable pressure from autoclaving.
      This method is simple, clean, inexpensive, and easily implemented, and it can be
      applied alongside other existing methods of oxygen mass transfer enhancement.

PMID- 1368262
TI  - Setting a sequence to sequence a sequence.

PMID- 1368263
TI  - Sequencing and mapping efforts in "model organisms".

PMID- 1368264
TI  - Biotech vaccines' problematic promise.

PMID- 1368265
TI  - Is an AIDS vaccine possible?

PMID- 1368266
TI  - Loops and secondary structure mimetics: development and applications in basic
      science and rational drug design.
AB  - One goal of protein design and structural biochemistry is the reduction of
      complex molecules to small functional units that are amenable to high resolution
      analysis and rapid modification. We have developed a variety of small molecules
      which biochemically and biologically mimic the combining sites of proteins of the
      immunoglobulin superfamily. The chemical and biological properties of peptide
      mimetics suggest that these analogs can be used as indicators for new
      pharmaceutical agents. Mimetics are powerful tools for the study of molecular
      recognition since they are small in size, maintain solubility in physiologic
      fluids and are amenable to detailed structural studies. As such, they represent a
      step toward the rational design of low molecular weight non-peptide
      pharmaceutical agents devoid of some of the shortcomings of conventional
      peptides. Here we discuss the rationale and approaches for the development of
      these molecules, and their current and future applications.

PMID- 1368267
TI  - By-passing immunization: building high affinity human antibodies by chain
      shuffling.
AB  - Diverse antibody libraries can be displayed on the surface of filamentous
      bacteriophage, and selected by panning of the phage with antigen. This allows
      human antibodies to be made directly in vitro without prior immunization, thus
      mimicking the primary immune response. Here we have improved the affinity of one
      such "primary" antibody by sequentially replacing the heavy and light chain
      variable (V) region genes with repertoires of V-genes (chain shuffling) obtained
      from unimmunized donors. For a human phage antibody for the hapten 2-phenyloxazol
      5-one (phOx) (Kd = 3.2 x 10(-7) M), we shuffled the light chains and isolated an
      antibody with a 20 fold improved affinity. By shuffling the first two
      hypervariable loops of the heavy chain, we isolated an antibody with a further 15
      fold improved affinity. The reshuffled antibody differed in five of the six
      hypervariable loops from the original antibody and the affinity for phOx (Kd =
      1.1 x 10(-9) M) was comparable to that of mouse hybridomas from the tertiary
      immune response. Reshuffling offers an alternative to random point mutation for
      affinity maturation of human antibodies in vitro.

PMID- 1368269
TI  - Synthesis of a functional anti-phytochrome single-chain Fv protein in transgenic
      tobacco.
AB  - We have expressed a synthetic gene that encodes an antigen-binding single-chain
      FV protein (scFV) in transgenic tobacco plants. The scFV gene was created by
      polymerase chain reaction (PCR) amplification of the variable domain coding
      regions from a mouse monoclonal hybridoma cell line. The monoclonal cell line
      secretes an IgG1 antibody that binds to the plant regulatory photoreceptor
      protein, phytochrome. The cloned scFV gene was expressed initially in Escherichia
      coli and shown to produce a 28 kD, phytochrome-binding binding scFV protein.
      Transgenic tobacco plants expressing the scFV gene were also found to produce a
      functional scFV protein, and seeds from transgenic R1 progeny displayed aberrant
      phytochrome-dependent germination. The scFV from transgenic tobacco could be
      isolated, to near homogeneity, by a single phytochrome-Sepharose affinity
      chromatography step.

PMID- 1368268
TI  - Production of biologically active recombinant human lactoferrin in Aspergillus
      oryzae.
AB  - We report the production of recombinant human lactoferrin in Aspergillus oryzae.
      Expression of human lactoferrin (hLF), a 78 kD glycoprotein, was achieved by
      placing the cDNA under the control of the A. oryzae alpha-amylase promoter and
      the 3' flanking region of the A. niger glucoamylase gene. Using this system, hLF
      is expressed and secreted into the growth medium at levels up to 25 mg/l. The
      recombinant lactoferrin is indistinguishable from human milk lactoferrin with
      respect to its size, immunoreactivity, and iron-binding capacity. The recombinant
      protein appears to be appropriately N-linked glycosylated and correctly processed
      at the N-terminus by the A. oryzae secretory apparatus. Lactoferrin is the
      largest heterologous protein and the first mammalian glycoprotein expressed in
      the Aspergillus system to date. Hence, this expression system appears suitable
      for the large-scale production and secretion of biologically active mammalian
      glycoproteins.

PMID- 1368270
TI  - Sequence-specific cleavage of protein fusions using a recombinant Neisseria type
      2 IgA protease.
AB  - Sequence-specific enzymatic cleavage of protein fusions is an important
      application in recombinant protein technology. We have used the Neisseria type 2
      IgA protease (EC 3.4.24.13), produced and secreted by Escherichia coli host
      cells, for efficiently processing polypeptides at authentic or engineered target
      sites. In different substrates, the microbial protease specifically cleaves the
      peptide bond distal to the second Pro residue of the sequence Yaa-Pro-/-Xaa-Pro,
      where Yaa stands for Pro (or rarely for Pro in combination with Ala, Gly or Thr)
      and Xaa stands for Thr, Ser or Ala. Highly specific proteolysis has been obtained
      not only with soluble and purified protein fusions but also with insoluble
      aggregates derived from cytoplasmic inclusion bodies. The sequence-specificity
      and simple production of the recombinant IgA protease make it a versatile tool
      for the in vitro processing of recombinant proteins.

PMID- 1368271
TI  - A low cost microprocessor-controlled electrofusion and electroporation system.
AB  - An important recent development in the field of biotechnology has been the use of
      high electric fields to render cell membranes temporarily permeable
      (electroporation). Cells in this state are receptive to gene transfer or can be
      induced to fuse with each other (electrofusion) to form hybrid cells containing
      the combined characteristics of the parent cells. A major reason for fusing cells
      is to form hybridoma cells which secrete monoclonal antibodies. A problem for
      research workers has been the high price of some of the electrofusion equipment.
      This problem has been addressed by designing a device that is inexpensive (less
      than $800 Canadian) and can be assembled by an electronics technician. The system
      uses a Radio Shack CoCo III microcomputer which is programmed in BASIC and
      controls the electroporation voltage pulse amplitude (25-500 V) and duration (2
      275 microseconds) to an electrofusion chamber; this yields electric field
      strengths of 0.25-5 kV cm-1 for a 0.1 cm electrode spacing. The system is capable
      of delivering pulse currents up to 3 A. This paper provides technical details on
      how to construct an instrument that has greater flexibility at less cost than
      comparable commercially available instruments.

PMID- 1368272
TI  - Spectrophotometric determination of ephedrine HCl, cinchonine HCl,
      chlorpheniramine maleate, atropine sulphate and diphenhydramine HCl by solvent
      extraction of reineckate complexes.
AB  - A spectrophotometric method for the determination of some alkaloids (namely
      ephedrine HCl, cinchonine HCl, chlorpheniramine maleate, atropine sulphate and
      diphenhydramine HCl) as separate compounds as well as in pharmaceutical
      preparations through the formation of their ion-pair (reineckate complexes) is
      described. These complexes were prepared and the final products were extracted
      with nitrobenzene in situ. The optimum conditions for complete extraction were
      evaluated by investigating the nature of solvent, pH, time of shaking,
      temperature and reineckate concentrations. The absorption spectra of the
      extracted organic layer were measured at 520 nm. The extraction constants were
      calculated and found to have a mean of log KE congruent to 2. The application of
      the present method was compared with the accepted pharmacopoeia method and the
      effects of some interfering ions were also studied.

PMID- 1368273
TI  - Synthesis and application of novel sulpha drugs based on quinoxaline-2-one and/or
      quinoxaline-2-thione.
AB  - Some novel azo-Sulpha drugs as 3-methyl-N-azo-(4'-substituted heterocyclo-benzene
      sulphamoyl) quinoxaline-2-ones (1-11) and 3-methyl-N-azo-(4'-substituted
      heterocyclo-benzene-sulphamoyl)-quinoxaline-2-thiones (1'-11') were synthesized
      by coupling 4'-substituted heterocyclo-benzene-sulphamoyl diazonium acetates with
      3-methyl-N-(1H)-quinoxaline-2-one and/or with 3-methyl-N(1H) quinoxaline-2-thione
      in acid medium. The corresponding iron (III) (1a-11, 1'a-11'a) copper (II) (1b
      1b'-7b') and mercury (II) (1c-11c, 1c'-11c) chelates were also prepared in a 1:1
      metal-to-ligand ratio. The ligands and their chelates were characterized on the
      basis of microanalysis, UV, IR and H'-NMR spectrometry, and were tested in vitro
      for their antibacterial and antifungal activities.

PMID- 1368274
TI  - Cleavage-site motifs in protein targeting sequences.

PMID- 1368275
TI  - Is GRP78 a sensor of cellular secretory activity?

PMID- 1368276
TI  - Complications of RNA heterogeneity for the engineering of virus vaccines and
      antiviral agents.

PMID- 1368277
TI  - The molecular biology of pathogenesis in Ustilago maydis.

PMID- 1368278
TI  - Structural constraints on residue substitution.

PMID- 1368279
TI  - Molecular and functional analysis of the A mating type genes of Coprinus
      cinereus.

PMID- 1368280
TI  - Physical mapping of human chromosomes.

PMID- 1368281
TI  - The quaternary structures of SV40 large T antigen and tumor suppressor p53:
      analysis by gel electrophoresis.

PMID- 1368282
TI  - Assembly of antibodies and mutagenized variants in transgenic plants and plant
      cell cultures.

PMID- 1368283
TI  - Large-scale plant cell culture: methods, applications and products.

PMID- 1368284
TI  - Mammalian cell culture processes.
AB  - Over the past year, mammalian cell culture research has been aimed at
      investigating the influence of culture conditions on viability, productivity and
      the consistency of post-translational modifications. Studies of the effect of
      medium conditions and the development of kinetic models are being made in
      relation to current efforts to develop fed-batch strategies that will optimize
      recombinant protein production processes. Recent advances have included novel
      biosensor and bioreactor developments. New technologies have also been applied to
      investigate high cell density bioreactor and culture conditions.

PMID- 1368285
TI  - New materials and technology for cell immobilization.
AB  - The choice of the most effective manner in which to operate an immobilized cell
      system is both complicated and, to some extent, a matter of guesswork. There is
      increasing awareness of the factors affecting reactor choice, and present work is
      aimed at making reactor performance more predictable.

PMID- 1368286
TI  - New applications of biocatalysts.
AB  - The development of new biocatalytic applications continues to advance in several
      directions. Over the past year, new enzymes have been discovered and their
      potential in biocatalyst applications has been researched. In addition, new
      chemical and genetic modifications have been made in the development of novel
      fermentation processes.

PMID- 1368287
TI  - Enzymology in monophasic organic media.
AB  - Over the past year, an important area of research has been directed towards the
      fundamental aspects of enzymes and new applications of enzymology in monophasic
      organic media. Much of this research has focused on the factors that influence
      enzymatic catalysis in monophasic organic solvents, including the importance of
      enzyme-associated water, and the effect of organic solvents on enzyme structure
      and thermodynamic features. From an applications perspective, new advances in the
      use of enzymes in organic and polymer syntheses and optical resolutions have been
      made.

PMID- 1368288
TI  - Integrated product formation and recovery in fermentation.
AB  - Fermentation processes are hampered by a variety of problems originating from the
      accumulation of products in the fermenter. Integration of fermentation and a
      primary product separation step can accelerate the product formation, improve the
      product yield, and facilitate downstream processing. The advantages of integrated
      bioprocesses, however, are counteracted by the incompatibility of the
      subprocesses. Over the past few years, research in this field has been directed
      towards the development of engineering tools to reduce integration problems, to
      select a suitable approach, and to predict the feasibility of the integrated
      process. More fundamental knowledge about metabolic pathways, control mechanisms,
      and process dynamics is needed in order to optimally design integrated systems.

PMID- 1368289
TI  - Plant responses to environmental stress.
AB  - Considerable progress is being made in identifying genes that are important for
      tolerance to abiotic stress and in defining stress-responsive gene promoters and
      signal-transduction pathways. Although genetically engineered crop plants with
      greater resistance to environmental stress have not yet been produced, research
      is at a turning point where correlative changes can now be tested for
      effectiveness in conferring stress tolerance.

PMID- 1368290
TI  - Biochemical engineering.

PMID- 1368291
TI  - Plant biotechnology.

PMID- 1368292
TI  - High cell density and high-productivity microbial fermentation.
AB  - Several interesting approaches to high cell density systems, molecular strategies
      coupled with fermentation technology, and updated traditional strategies have
      been used in the past year to obtain high productivity in the formation of
      important products. The most significant advances include new strategies for
      controlling high cell density fermentation reactors and expression of
      heterologous proteins in different strains of yeasts.

PMID- 1368293
TI  - Large-scale insect cell culture.
AB  - Significant advances have been made over the past year in our understanding of
      the protective mechanisms, both fluid-mechanical and biological, of media
      additives on suspended animal cells. The degree of protection offered by
      different additives, such as pluronic polyol, appears to be cell-type dependent,
      varying quite dramatically not only between insect and mammalian cells, but also
      between different insect cell lines themselves.

PMID- 1368294
TI  - Evidence for the existence of isozymes of glucose isomerase from Streptomyces
      phaeochromogenes.
AB  - Glucose isomerase from Streptomyces phaeochromogenes was purified from a
      commercial preparation, Swetase, by DEAE-cellulose, Bio-Gel A-0.5 m, and
      hydroxyapatite column chromatographies. It was found to be 2 fractions; F-A, not
      adsorbed on hydroxyapatite and F-B, adsorbed on hydroxyapatite. They were
      homogeneous in ordinary and SDS-PAGE and had similarities in some enzymatic and
      physico-chemical properties. The differences, however, were found in the N
      terminal amino acid, which was only serine for F-A while it was serine and
      alanine for F-B, and also in their peptide mapping patterns of digests with
      trypsin, Achromobacter protease I, and cyanogen bromide. The results suggest that
      glucose isomerase from S. phaeochromogenes was composed of the two kinds of
      isozymes and that each of isozymes was a tetramer constituted of non-identical
      subunits.

PMID- 1368295
TI  - Establishment of a host-vector system in Lactobacillus helveticus with beta
      galactosidase activity as a selection marker.
AB  - A host-vector system was established in Lactobacillus helveticus with beta
      galactosidase activity as a selection marker. Plasmid pBG10 was constructed by
      joining the beta-galactosidase gene from L. bulgaricus, the promoter region of
      the erythromycin resistance gene from pAM beta 1, the replication region of
      pBR329, and the replication region of the L. helveticus cryptic plasmid pLJ1. L.
      helveticus SBT2195 (Lac- mutant), transformed with pBG10, was selected on skim
      milk plates. The structural gene of alpha-amylase (1536 bp) from Bacillus
      licheniformis, inserted downstream of the promoter region of the erythromycin
      resistance gene of pBG10, was expressed in L. helveticus SBT2195. Plasmid pBG10
      is a food-grade and expression vector in L. helveticus.

PMID- 1368297
TI  - Structures of N-linked oligosaccharides of microsomal glycoproteins from
      developing castor bean endosperms.
AB  - The structures of sugar chains of the glycoproteins from the microsomal fraction
      of developing castor bean endosperms have been analyzed. The structural analyses
      were done by a fluorescence method combined with component analysis,
      exoglycosidase digestions, partial acetolysis, Smith degradation, and 1H-NMR
      spectroscopy. The estimated structures fell into three categories; the first was
      oligomannose-type, the second xylomannose-type, the third complex-type. Among
      these oligosaccharides, Man3Fuc1Xyl1GlcNAc2 (M3FX) and Man6GlcNAc2 (M6B) were the
      major structures. The structures of Man4GlcNAc2 (M4C) and Man4Xyl1GlcNAc2 (M4X)
      have also been found in the microsomal glycoproteins of the developing bean
      endosperms. These results could indicate that the structures of M4C, M4X, and
      M3FX are formed in the stage of sugar chain processing in the microsomal
      fraction, in which oligomannose-type sugar chains are modified into complex-type
      ones by several kinds of processing enzymes.

PMID- 1368296
TI  - Inhibition by lactoferrin and kappa-casein glycomacropeptide of binding of
      Cholera toxin to its receptor.
AB  - Inhibition from binding of Cholera toxin (CT) to Chinese hamster ovary (CHO)-K1
      cells and ganglioside GM1 by lactoferrin (Lf) and kappa-casein glycomacropeptide
      (GMP) from cow's milk was examined. Both Lf and GMP effectively reduced the CT
      derived morphological changes in CHO-K1 cells. The competitive binding assay
      demonstrated that both Lf and GMP inhibited the binding of CT to GM1, although
      their affinity for CT was lower than that of GM1. The inhibitory effect of Lf and
      GMP seemed to be attributed to their terminal sialic acid, although the sugar
      chain sequence only partially fitted to the CT-receptor.

PMID- 1368298
TI  - Sequence analysis of replication origin of plasmid pLS11 of Bacillus subtilis IFO
      3022.
AB  - The structure of a 1.6-kb SphI-HindIII DNA sequence necessary and sufficient for
      the replication of a 8.6-kb plasmid pLS11 of Bacillus subtilis IFO 3022, which is
      responsible for gamma-polyglutamate production, has been characterized by using a
      trimethoprim (Tmp)-resistance gene derived form B. subtilis TTK24 chromosomal DNA
      as a selective marker. The 1.6-kb DNA sequence contains a rep gene encoding the
      protein (333 amino acids) essential for initiation of replication and a possible
      origin of replication. The predicted REP protein of pLS11 has an overall homology
      with the REP proteins of pUH1 (74.8% identity), pBAA1 (92.8%), and pFTB14 (78.7%)
      in Bacillus spp., pLP1 (42.1%) and pLAB1000 (36.3%) in Lactobacillus spp., and
      pUB110 (35.3%) and pC194 (37.4%) in Staphylococcus aureus, but has not any
      similarity with the REP protein of the staphylococcal plasmid pT181.

PMID- 1368299
TI  - Formation of a transfer product from stevioside by the cultures of Actinomycete.
AB  - An Actinomycete, strain K-128, which was isolated from soil, formed a transfer
      product when the strain was cultured in a medium containing both stevioside and
      curdlan. The transfer product in culture broth was separated by DIAION HP-20
      column and TOYOPEARL HW-40F column chromatographies. From structural studies, the
      transfer product was identified as C13-O-beta-6(2)-beta-glucosylsophorosyl-C19-O
      beta-glucopyranosyl steviol. This product was the first to be obtained by a
      culture of an Actinomycete.

PMID- 1368300
TI  - Galactosylation at side chains of branched cyclodextrins by various beta
      galactosidases.
AB  - The galactosyl transfer reaction to branched cyclodextrins (CDs) was investigated
      using lactose as a donor substrate and branched CDs as acceptors by various beta
      galactosidases. Bacillus circulans beta-galactosidase synthesized galactosyl
      transfer products to branched CDs, of which the galactose residues were linked at
      side chains of branched CDs, not directly at CD rings. Aspergillus oryzae and
      Penicillium multicolor beta-galactosidases also produced derivatives
      galactosylated at side chains of branched CDs. The structures of main
      transgalactosylation products of branched CDs by these beta-galactosidases seem
      to be different from those by B. circulans beta-galactosidase, judging from the
      retention times on high performance liquid chromatography.

PMID- 1368301
TI  - Purification and characterization of a thermostable alkaline protease from
      alkalophilic Thermoactinomyces sp. HS682.
AB  - Protease secreted into the culture medium by alkalophilic Thermoactinomyces sp.
      HS682 was purified to an electrophoretically homogeneous state through only two
      chromatographies using Butyl-Toyopearl 650M and SP-Toyopearl 650S columns. The
      purified enzyme has an apparent relative molecular mass of 25,000 according to
      gel filtration on a Sephadex G-75 column and SDS-PAGE and an isoelectric point
      above 11.0. Its proteolytic activity was inhibited by active-site inhibitors of
      serine protease, DFP and PMSF, and metal ions, Cu2+ and Hg2+. The enzyme was
      stable toward some detergents, sodium perborate, sodium triphosphate, sodium-n
      dodecylbenzenesulfonate, and sodium dodecyl sulfate, at a concentration of 0.1%
      and pH 11.5 and 37 degrees C for 60 min. The optimum pH was pH 11.5-13.0 at 37
      degrees C and the optimum temperature was 70 degrees C at pH 11.5. Calcium
      divalent cation raised the pH and heat stabilities of the enzyme. In the presence
      of 5 mM CaCl2, it showed maximum proteolytic activity at 80 degrees C and
      stability from pH 4-12.5 at 60 degrees C and below 75 degrees C at pH 11.5. The
      stabilization by Ca2+ was observed in secondary conformation deduced from the
      circular dichroic spectrum of the enzyme. The protease hydrolyzed the ester bond
      of benzoyl leucine ester well. The amino acid terminal sequence of the enzyme
      showed high homology with those of microbial serine protease, although alanine of
      the NH2-terminal amino acid was deleted.

PMID- 1368302
TI  - Molecular stability of chicken and rabbit immunoglobulin G.
AB  - Molecular stability of chicken egg yolk immunoglobulin G (IgY) and that of rabbit
      IgG were compared by measuring antibody activities and conformational changes.
      Stability of rabbit IgG to acid denaturation was much higher than that of IgY.
      Conformation of the IgY molecule was readily changed in acidic conditions,
      resulting in a rapid loss of antibody activity. Much less stable natures of IgY
      to heat-treatment and guanidine-HCl denaturation than rabbit IgG were also
      observed. Differences in the structure between the two immunoglobulins that might
      participate in their different stability were inferred from their amino acid
      sequence data. Importance of the intramolecular disulfide linkage in the rabbit
      light chain and some other structural differences were suggested.

PMID- 1368303
TI  - Purification and characterization of serine proteinase inhibitors form gourd
      (Lagenaria leucantha Rusby var. Gourda Makino) seeds.
AB  - Gourd seed inhibitors were purified in the following manner: gourd seeds were
      ground and extracted with 10 mM ammonium carbonate, pH 7.8. The extract was
      precipitated with 65-90% acetone and the acetone precipitates were gel filtered
      in a Cellulofine GCL-90-m column. Fractions of 3000 Da showing trypsin inhibitory
      activity were combined and purified further by ion exchange and reversed phase
      chromatographies. Three inhibitors, LLTI-I, II, and III were thus purified to
      homogeneity and the amino acid sequences of these inhibitors were: [sequence: see
      text] The exact sequences are unique but very similar to proteinase inhibitors
      belonging to the squash family. Based on the sequence, it is assumed that the
      peptide bond (Arg-Ile) found in the three inhibitors is the reactive site for
      trypsin. The Ki values estimated for complexes of LLTI-I, II, and III with bovine
      trypsin were 3.6 x 10(-10) M, 6.5 x 10(-11) M, and 3.0 x 10(-11) M, respectively.

PMID- 1368306
TI  - N-terminal amino acid sequence of the chlorophyll-binding protein CP-47 of
      Photosystem 2 in the thermophilic cyanobacterium Synechococcus elongatus.

PMID- 1368304
TI  - Secretion of mono- and diacylglycerol lipase from Penicillium camembertii U-150
      by Saccharomyces cerevisiae and site-directed mutagenesis of the putative
      catalytic sites of the lipase.
AB  - Yeast cells carrying intronless mono- and diacylglycerol lipase (MDGL) genes,
      constructed by recombination of the genomic gene and cDNA, secreted MDGL into the
      culture supernatant. Most of the yeast MDGL were extensively glycosylated while
      they had a similar glyceride specificity to that of native MDGL. Site-directed
      mutagenesis was used to directly confirm the involvements in enzyme activity of
      the presumptive amino acid residues to form the catalytic center of MDGL. These
      residues were conserved in the primary structure alignment of a lipase family
      from filamentous fungi. Mutant lipase proteins in which Ser83, Ser145, or His259
      was replaced with glycine were secreted by yeast transformants as inactive
      proteins. Mutant proteins replacing Asp199 with glycine or asparagine were not
      detected in the culture supernatant. Replacing other two highly conserved
      aspartic acids (at positions 232 and 243) with glycine did not render the enzyme
      inactive. These results indicate that Ser83, Ser145, and His259 in MDGL, are
      essential to enzyme activity. Asp199 is also likely to be involved.

PMID- 1368305
TI  - Enhancement of the thermostability of the alkaline protease from Aspergillus
      oryzae by introduction of a disulfide bond.

PMID- 1368307
TI  - Effects of exogenous methyl oleate on the biosynthesis of nigericin, a polyether
      carboxylic antibiotic, by Streptomyces hygroscopicus NRRL B-1865.

PMID- 1368308
TI  - Substrate specificity of thermostable alkaline protease from Bacillus sp. No. AH
      101.

PMID- 1368309
TI  - Effects of some L-rhamnosyl derivatives on the adsorption of phage PL-1 to the
      host Lactobacillus casei.

PMID- 1368310
TI  - Antitumor-active polysaccharides isolated from the fruiting body of Hericium
      erinaceum, an edible and medicinal mushroom called yamabushitake or houtou.

PMID- 1368311
TI  - Extracellular production of human immunoglobulin epsilon-chain/gamma 1-chain
      chimeric Fc polypeptide by Escherichia coli.

PMID- 1368312
TI  - Effect of depolymerized alginates on the growth of bifidobacteria.

PMID- 1368313
TI  - High-sensitivity peptide mapping with CE using laser-induced fluorescence
      detection.

PMID- 1368314
TI  - Protein separations on tentacle ion exchangers. Part II: Scale-up and loading
      study.

PMID- 1368315
TI  - Shaping up for a bright future: protein analysis and design.

PMID- 1368316
TI  - Message amplification phenotyping (MAPPing)--principles, practice and potential.
AB  - Message amplification phenotyping (MAPPing) is a sensitive polymerase chain
      reaction (PCR)-based technique for the rapid determination of the mRNA phenotype
      of small numbers of cells. Isolated mRNA is reverse-transcribed (RT) into DNA,
      and then the DNA fragments corresponding to proteins or genes of interest are
      specifically amplified by PCR. The technique, also called RT-PCR, has wide
      application in biology and medicine, and comparison with bioassays demonstrates
      that MAPPing saves significant time and material. The technique should be
      applicable to analyse mRNAs of virtually any tissue or cell type.

PMID- 1368317
TI  - Antisense oligonucleotides as antiviral agents.
AB  - Antisense oligonucleotides are an attractive potential alternative to
      conventional drugs as antiviral agents. A major advantage is the relatively
      simple rational design of oligonucleotides which should bind only to specific
      nucleic acid sequences, compared with conventional drugs which are frequently
      targeted against sites of unknown structure in proteins. Progress to date
      provides hope for the development of a new class of antiviral chemotherapeutics
      based on antisense oligonucleotides.

PMID- 1368318
TI  - Therapeutic challenges: does Glycobiology have a role?

PMID- 1368319
TI  - What's cooking? Optimizing bioprocess monitoring.

PMID- 1368320
TI  - A need to refocus research in the operation of fermenters?

PMID- 1368321
TI  - Antifungal drug development: the identification of new targets.
AB  - With the increasing prevalence of life-threatening systemic fungal infections in
      the human population, there is a need to develop new, more-effective antifungal
      agents. This, in turn, will depend upon the identification and exploitation of
      new antifungal targets--aspects of fungal cytology, metabolism and gene
      expression which are important for fungal pathogenesis, but which have no
      mammalian host counterpart. Such new targets have been identified through a
      combination of classical genetic, cytological and biochemical studies and are
      reviewed here, as is the potential for applying recombinant DNA techniques as a
      means of confirming the role of the identified gene products in pathogenesis.

PMID- 1368322
TI  - Bacillus subtilis and its relatives: molecular biological and industrial
      workhorses.
AB  - The non-pathogenic bacterium Bacillus subtilis, since its first reported genetic
      transformation in 1959, has become a model system for the study of many aspects
      of the biochemistry, genetics and physiology of Gram-positive bacteria, and
      particularly of sporulation and associated metabolism. Extensive knowledge of the
      molecular biology of B. subtilis has led to the recent development of this
      bacterium as a host for the industrial production of heterologous proteins.
      Although difficulties have been encountered, these are being systematically
      addressed and overcome.

PMID- 1368323
TI  - Synthesis of the five peptide derivatives needed to build the sequence
      corresponding to 1-30 of human epidermal growth factor (h-EGF).

PMID- 1368324
TI  - Total solution synthesis of human epidermal growth factor (h-EGF) by the assembly
      of nine building blocks.
AB  - Human epidermal growth factor (h-EGF) composed of 53 amino acids bearing three
      intramolecular disulfide bridges was synthesized by the maximum protecting
      solution method. The synthetic h-EGF coincided with recombinant h-EGF by reverse
      phase HPLC, and the sites of three intramolecular disulfide bridges were
      ascertained by a thermolytic digestion. The synthetic h-EGF possessed m/z 6215.7
      in its FAB-MS as expected, and exhibited compatible mitogenic activity.

PMID- 1368325
TI  - Stimulation of IgM production in human-human hybridoma HB4C5 cells by chitosan.
AB  - We screened for immunoglobulin production stimulating factors (IPSFs) in
      polysaccharides using human-human hybridoma cells, HB4C5, cultured in serum-free
      medium. Among polysaccharides, citrus pectin, locust bean gum, and chitosan
      stimulated IgM production of HB4C5 cells. Especially chitosan showed the
      strongest IPSF activity; 100 ng/ml of chitosan stimulated IgM production
      approximately 5-fold. Chitosan had several characteristics as IPSF, as follows.
      1) For the IPSF activity, 70-90% deacetylation was essential. 2) Chitosan
      oligomers (n = 5, 6, 7) and chitin oligomers (n = 5, 6, 7) showed no IPSF
      activities. 3) The IPSF activity of chitosan was inhibited by glucosamine, one of
      the constitutive sugars of chitosan. 4) Chitosan stimulated IgM production of
      human lymphocytes in serum-free culture, but not IgG or IgA, nor in serum
      supplemented culture.

PMID- 1368326
TI  - Molecular cloning and expression of a Streptomyces sarcosine oxidase gene in
      Streptomyces lividans.
AB  - A genomic library of Streptomyces sp. KB210-8SY, prepared in the plasmid vector
      pACYC184, was screened to obtain the gene encoding sarcosine oxidase with probes
      based on the amino acid sequence of the protein. A plasmid pSOXS13, which was
      isolated from a clone identified by hybridization with the probes, contained a
      8.4-kb insert of Streptomyces DNA. When the 2.0-kb MIuI/EcoRV DNA fragment of
      pSOXS13 was inserted into the Streptomyces vector pIJ680 and introduced into S.
      lividans, the transformants produced 100-fold more sarcosine oxidase
      intracellularly than KB210-8SY. The nucleotides of the 1.7-kb fragment containing
      the sarcosine oxidase gene were sequenced. An open reading frame encoded a mature
      sarcosine oxidase consisting of 388 amino acids, with a calculated molecular mass
      of 42,107 daltons.

PMID- 1368327
TI  - Production of dihydrofolate reductase by cloned Escherichia coli and its
      application to asymmetric synthesis of l-leucovorin.
AB  - We have investigated culture conditions for production of dihydrofolate reductase
      by Escherichia coli harboring a high expression plasmid, pTP64-1. Sorbitol
      addition and pH control were effective for the production of the enzyme in a jar
      fermentor. The enzyme was purified from a cell-free extract by column
      chromatographies on DEAE-Cellulofine and Superose Prep12 and showed a single band
      on SDS-polyacrylamide gel electrophoresis. The reduction of 200 mM dihydrofolate
      to 6(S)-tetrahydrofolate, an intermediate for l-leucovorin synthesis, was
      complete in 2 hr under anaerobic conditions, using 1.5 units/ml of the purified
      enzyme.

PMID- 1368329
TI  - Synthesis of a ganglioside GM3 analog containing a hydroxymethyl group in place
      of the carboxyl group in the N-acetylneuraminic acid unit.

PMID- 1368328
TI  - Characteristics of chymotrypsin modified with water-soluble acylating reagents
      and its peptide synthesis ability in aqueous organic media.
AB  - Several kinds of modified chymotrypsin were prepared with water-soluble acylating
      reagents, and their characteristics after hydrolyzing with unmodified
      chymotrypsin in aqueous-N,N'-dimethylformamide (DMF) media were compared. It was
      found that chymotrypsin (Csin), of which a 20% amino group was modified with a
      benzyloxycarbonyl group (Z(20)Csin), had more favorable characteristics than
      unmodified chymotrypsin with regard to hydrolytic activity in an aqueous DMF
      media. We also investigated the Z(20)Csin-catalyzed peptide synthesis in two
      different solution systems. In the one-layer system containing water and DMF,
      Z(20)Csin catalyzed the peptide bond formation in a higher yield than that by
      unmodifide chymotrypsin and enabled a synthetic reaction in even an 80% (v/v) DMF
      media, in which the hydrolytic reaction could not be carried out. Z(20)Csin
      catalyzed the condensation between some N-acyl amino acids or peptide derivatives
      and amino acids in 90% ethylacetate, 90% hexane or 50% benzene. This latter
      method employs a two-layer system, and the modified enzyme may be able to reduce
      the number of synthetic steps when preparing acyl peptides.

PMID- 1368330
TI  - Action pattern of Bacillus sp. no. 7-M chitosanase on partially N-acetylated
      chitosan.
AB  - The hydrolyzate of partially N-acetylated chitosan by Bacillus sp. No. 7-M
      chitosanase was separated by gel filtration on Bio-Gel P-2. Sugar compositions
      and sequences of the oligosaccharides were identified by exo-splitting with beta
      GlcNase, fast atom bombardment mass spectroscopy, and proton NMR spectroscopy. In
      addition to chitooligosaccharides, (GlcN)2, (GlcN)3, and (GlcN)4, hetero
      chitooligosaccharides such as (GlcN)2.GlcNAc.(GlcN)2, GlcN.GlcNAc.(GlcN)3,
      (GlcN)2.GlcNAc.(GlcN)3, and GlcN.GlcNAc.(GlcN)4 were detected. These results
      indicate that Bacillus sp. No. 7-M chitosanase is absolutely specific toward the
      GlcN.GlcN bonds in partially N-acetylated chitosan and at least three GlcN
      residues were necessary to the hydrolysis of chitosan by chitosanase.

PMID- 1368331
TI  - Solid-phase synthesis of [AsnA16]-, [AsnA22]-, [GlnA25]-, and [AsnA26]monellin,
      analogues of the sweet protein monellin.
AB  - In an attempt to delineate the binding site(s) of monellin to the receptor by
      means of a structure-taste relationship, we synthesized four monellin analogues,
      [AsnA16]-, [AsnA22]-, [GlnA25]-, and [AsnA26]-monellin, which were 7500, 750,
      2500, and 5500 times as sweet as sucrose on a weight basis, respectively. Among
      them, [AsnA22]monellin and [GlnA25]monellin were less sweet than monellin, and
      were susceptible to the HPLC conditions used. It can be concluded that Asp16,
      Asp22, Glu25, and Asp26 residues of the A chain did not participate in binding
      with the receptor, since the sweet taste was not removed by replacing the amino
      acid residues with Asn or Gln. It can also be concluded that Asp22 and Glu25 of
      the A chain may have participated in intramolecular binding, as was pointed out
      by Kim et al., since exchanging Asp22 and Glu25 of the A chain with Asn and Gln
      significantly decreased the stability in solution.

PMID- 1368332
TI  - Properties of agents that effectively entrap liquid lipids.
AB  - A droplet of an oil-in-water emulsion of methyl linoleate in a saccharide or
      protein solution that contained with a surfactant, a stabilizer, or both was
      dehydrated by drying equipment for a single droplet that resembled a spray drier.
      The lipid exposed on the surface of dehydated samples was extracted and measured
      by gas chromatography. Gum arabic or gelatin without additives resulted in little
      lipid being exposed; they were good entrapping agents. Little lipid was exposed
      with a pullulan solution containing lecithin, sugar ester,
      carboxymethylcellulose, or sodium caseinate but much was exposed with a
      maltodextrin solution containing any of the surfactants tested. When both the
      surfactant lecithin and the stabilizer xanthan gum were added to the emulsion
      prepared in a maltodextrin solution, lipid was not detected. The results
      suggested that effective entrapping agents of liquid lipids cause much
      emulsification, stabilize the emulsion (that is, they cause the continuous phase
      to be very viscous), and create a dehydrated matrix of fine, dense network
      layers.

PMID- 1368333
TI  - Cloning, expression, and characterization of a minor alkaline protease from
      Bacillus sp. no. AH-101.

PMID- 1368334
TI  - Nucleotide sequence of the gene that encodes a neopullulanase from an
      alkalophilic Bacillus.

PMID- 1368335
TI  - Colorimetric measurement of angiotensin I-converting enzyme inhibitory activity
      with trinitrobenzene sulfonate.

PMID- 1368337
TI  - Synthesis of a ganglioside GM3 position isomer, N-acetylneuraminosyl-alpha (2---
      6)-lactosyl-beta(1----1)-ceramide.

PMID- 1368336
TI  - Trypsin hydrolysis of the Tyr(42)-Ser(43) bond, the chymotrypsin reactive-site
      peptide bond, of faba bean Bowman-Birk type inhibitor.

PMID- 1368338
TI  - Nucleotide sequence of a cDNA that encodes a rice prolamin.

PMID- 1368339
TI  - Radicicol, an agent inducing the reversal of transformed phenotypes of src
      transformed fibroblasts.

PMID- 1368340
TI  - NADPH regeneration by glucose dehydrogenase from Gluconobacter scleroides for l
      leucovorin synthesis.
AB  - A new process for (6S)-tetrahydrofolate production from dihydrofolate was
      designed that used dihydrofolate reductase and an NADPH regeneration system.
      Glucose dehydrogenase from Gluconobacter scleroides KY3613 was used for recycling
      of the cofactor. The reaction mixture contained 200 mM dihydrofolate, 220 mM
      glucose, 2 mM NADP, 14.4 U/ml dihydrofolate reductase, and 14.4 U/ml Glucose
      dehydrogenase, and the reaction was complete after incubation at pH 8.0, and 40
      degrees C for 2.5 hr. With (6S)-tetrahydrofolate as the starting material, l
      leucovorin was synthesized via a methenyl derivative. The purity of the l
      leucovorin was 100%, and its diastereomeric purity was greater than 99.5% d.e. as
      the (6S)-form.

PMID- 1368341
TI  - Cloning and sequence analysis of cDNA encoding Rhizopus niveus lipase.
AB  - Complementary DNA encoding Rhizopus niveus lipase (RNL) was isolated from the R.
      niveus IF04759 cDNA library using a synthetic oligonucleotide corresponding to
      the amino acid sequence of the enzyme. A clone, which had an insert of 1.0
      kilobase pairs, was found to contain the coding region of the enzyme. The lipase
      gene was expressed in Escherichia coli as a lacZ fusion protein. The mature RNL
      consisted of 297 amino acid residues with a molecular mass of 32 kDa. The RNL
      sequence showed significant overall homology to Rhizomucor miehei lipase and the
      putative active site residues were strictly conserved.

PMID- 1368342
TI  - Cloning and nucleotide sequence of a frxC-ORF469 gene cluster of Synechocystis
      PCC6803: conservation with liverwort chloroplast frxC-ORF465 and nif operon.
AB  - A gene, frxC, which is unique to the chloroplast genome of the liverwort
      Marchantia polymorpha, has sequence similarity to nifH, the product of which is
      an iron protein of a nitrogenase. Although frxC is expressed to produce a protein
      in liverwort chloroplasts, its function is not known. Using a probe of liverwort
      chloroplast DNA, a 10.1-kb region containing a gene cluster consisting of open
      reading frames (ORF278-frxC-ORF469-ORF248) was isolated from the cyanobacterium
      Synechocystis PCC6803. In this region, frxC and ORF469 showed sequence
      similarities to liverwort chloroplast frxC (83%) and immediately downstream
      ORF465 (74%), respectively. Synechocystis frxC showed 31% amino acid sequence
      identity with nifH1 from Clostridium pasteurianum. Additionally, Synechocystis
      ORF469 showed a sequence similarity (19% identity) to C. pasteurianum nifK
      product, which is the beta subunit of a molybdenum-iron protein of a nitrogenase
      complex. Conservation of the gene arrangement between liverwort and Synechocystis
      suggests that the liverwort chloroplast frxC-ORF465 cluster may have evolved from
      an ancestor common to Synechocystis, and that these two genes may have been
      transferred to the nuclear genome in tobacco and rice during evolution.

PMID- 1368343
TI  - Characterization of carbonic anhydrase isozyme CA2, which is the CAH2 gene
      product, in Chlamydomonas reinhardtii.
AB  - From high-CO2 (5% CO2) grown unicellular green alga, Chlamydomonas reinhardtii,
      carbonic anhydrase (CA) was isolated by affinity chromatography and
      characterized. Isolated CA was identified as an isozyme (CA2) which is the
      product from the second gene CAH2 by peptide sequencing. The CA2 was inactivated
      by dithiothreitol. This treatment caused dissociation of CA2 into the large (38
      kDa) and small subunits (4243 Da). The molecular mass of the CA2 holoenzyme
      measured by low-angle laser light-scattering photometry and precision
      differential refractometry combined with gel-filtration HPLC was 87.9 kDa. These
      results and gene structure indicate that CA2 is a heterotetramer consisting of
      two large and two small subunits linked by disulfide bonds like CA1, which is the
      CAH1 gene product. The specific activity of CA2 purified by anion-exchange HPLC
      was 3300 units per mg protein, which was approximately 1.6 times higher than that
      of CA1. Therefore, it was concluded that two structurally related isozymes, CA1
      and CA2, are present in the wild type cells of C. reinhardtii and differentially
      regulated by the atmospheric CO2 concentration.

PMID- 1368344
TI  - Production of human epidermal growth factor by Bacillus brevis increased with use
      of a stable plasmid from B. brevis 481.

PMID- 1368345
TI  - Action of levan fructotransferase of Arthrobacter ureafaciens on a mixture of
      branched levanpentasaccharides.

PMID- 1368346
TI  - Rotihibin A, a novel plant growth regulator, from Streptomyces ap.

PMID- 1368347
TI  - Antischistosomal activities of sesquiterpene lactones and steroid glucosides from
      Vernonia amygdalina, possibly used by wild chimpanzees against parasite-related
      diseases.

PMID- 1368348
TI  - A highly sensitive enzyme-linked immunosorbent assay for Clostridium perfringens
      enterotoxin.
AB  - A highly sensitive enzyme-linked immunosorbent assay (ELISA) for quantitation of
      Clostridium perfringens enterotoxin (CPE) by a sandwich method with polystyrene
      beads was elaborated. The ELISA was very sensitive with a detection limit of 1
      pg/ml of CPE. Clostridium perfringens culture fluid did not interfere with the
      assay. This ELISA may be useful for the mass screening for Cl. perfringens
      producing small amounts of CPE.

PMID- 1368349
TI  - A fuzzy logic controller.
AB  - This paper describes a fuzzy sets method which is very useful for handling
      uncertainties and essential for knowledge acquisition of a human expert. Kinetics
      of a reactor is often complex and not trivial to describe by mathematical
      equations. Reactor control by traditional control technology is therefore
      difficult. A novel technology is presented. In the following a fuzzy inference
      (approximate reasoning) is used for decision making in analogy to human thinking,
      facilitating a more sophisticated control. Readers of this paper do not need any
      advanced mathematics beyond the four basic operations in arithmetic (+, -, x,
      divided by) and using the maximum and minimum values. This fuzzy inference is
      introduced to construct a fuzzy logic controller which is suitable for a
      nonlinear, multivariable and time variant system applied to a bioreactor.

PMID- 1368350
TI  - Biochemical switching device: biomimetic approach and application to neural
      network study.
AB  - There are many examples of enzymes that share substrates or cofactors in a cyclic
      manner. Techniques have been developed that use cyclic enzyme systems to assay
      quantitatively small amounts of biochemical substances (cofactor, substrate),
      however, only a few studies of the control of these systems have been published.
      The author previously showed with computer simulations that cyclic enzyme systems
      have the reliability of ON-OFF types of operation (McCulloch-Pitts' neuronic
      equation) capable of storing short-memory, and the applicability for a switching
      circuit in a biocomputer. This paper introduces a unique switching mechanism of
      cyclic enzyme system (basic switching element), and next, building the integrated
      biochemical switching system being composed of the basic switching element, shows
      the physiological phenomenon termed 'selective elimination of synapses' generally
      produced as a result of low-frequency train of electrical stimuli to the synapses
      (Kuroda, Y. 1989) Neurochem. Int. 14, 309-319).

PMID- 1368351
TI  - The way to adequate control of microbial processes passes via real-time knowledge
      based supervision.
AB  - Knowledge-based supervision is viewed as a major tool for achieving high
      performance control of microbial processes. By providing an adequate insight into
      the integral state of the cell culture, knowledge-based supervisory systems allow
      for monitoring and handling various important phenomena which usually remain
      outside the scope of the conventional control approach. The present paper focuses
      on the development of a computer system for knowledge-based supervision of
      bioprocesses. Its application to the control of fed-batch cultivation of
      recombinant Escherichia coli for phenylalanine production is also discussed.

PMID- 1368352
TI  - Fuzzy reasoning system for fault diagnosis of physiological activities in a
      cultivating process.
AB  - Aiming at development of a system which supports cultivating operations, a method
      to diagnose physiological activities in a cultivating process is presented, and a
      fuzzy expert system for diagnosing Lactobacillus casei cultivating process is
      implemented in this paper. This system can calculate specific rates of cell
      growth, substrate consumption, and product formation with measuring cell mass
      concentration, substrate concentration, and product concentration by using a
      turbidity sensor and HPLC. A database is implemented, where standard curves on
      specific rates representing characteristics of microorganisms are stored
      according to normalized substrate consumption. Comparing the calculated specific
      rates with standard values derived from the database, the system diagnoses
      physiological activities of the microorganisms. As a case study, a knowledge base
      for diagnosing lactic acid production process is implemented. The use of fault
      diagnosis on pH malfunctions by the expert system proves its reasonable
      performance.

PMID- 1368353
TI  - Control of enzyme properties in supramolecular systems.
AB  - The study deals with stability and activity of enzymes in supramolecular systems.
      Acid phosphatase (EC 3.1.3.2) has been studied as model enzyme. The organic phase
      is rich in C2-C4 acetates. Didodecyldimethylammonium chloride (DD-DACl) has been
      mainly used as ionic surfactants. The rate of enzyme inactivation is smaller than
      in buffer and is less dependent on storage temperature. Specific activity of the
      enzyme is lowered because of a less affinity towards the substrate and of
      reduction of maximal velocity.

PMID- 1368355
TI  - Improving purification of recombinant ribonuclease T1.
AB  - Purification of recombinant RNase T1 and its mutants has been improved by
      optimizing bacterial growth conditions, periplasmic fraction preparation and the
      use of a precolumn. The main part of the chromatographic separation could be
      automated due to the reproducibility of the procedure.

PMID- 1368354
TI  - Invertase activity of Saccharomyces cerevisiae cells entrapped in poly (2
      hydroxyethyl methacrylate) gels: kinetic and thermostability study in membrane
      reactors.
AB  - Films of poly (2-hydroxyethyl methacrylate) with entrapped yeast cells have been
      prepared and characterized in membrane reactors. Two concentrations, 5 and 10%
      w/w, of crosslinking agent ethylene dimethacrylate are used. The invertase
      activity is monitored between 30 and 55 degrees C in the range of sucrose
      concentration from 40 to 200 mM and during almost 600 h of operation. Comparison
      is also made with the behaviour of free cells and small size particles (less than
      115 mesh) of poly-HEMA immobilized cells. The results show that the whole
      membrane volume is not involved in substrate permeation and a combined diffusion
      reaction rate controlling mechanism holds. An unusual dependence of reaction rate
      on bulk pH is observed. In the range of pH from 4.0 to 6.0, invertase activity in
      films continuously increases while two distinctive maxima for free yeast cells
      (pH 4.75) and for small particles of poly-HEMA-immobilized yeast cells (pH 4.5)
      are observed.

PMID- 1368356
TI  - Computer-assisted selection of oligonucleotides and determination of critical
      parameters. For their use in molecular biology.

PMID- 1368357
TI  - Applications of electroporation in biotechnology.

PMID- 1368358
TI  - Detection of hemoglobin in serum products.

PMID- 1368359
TI  - Structures of elicitin isoforms secreted by Phytophthora drechsleri.
AB  - Most of the phytopathogenic fungi Phytophthora secrete holoproteins (elicitins)
      responsible for the incompatible reaction and systemic leaf necroses on tobacco.
      We found that Phytophthora drechsleri produces several elicitin isoforms of
      various toxicity on tobacco. The CD spectra showed that their secondary structure
      was largely conserved, exhibiting ca 50% alpha-helix and little or no beta
      structure. These 98 residue proteins were sequenced and compared with other known
      elicitins. Only one point mutation correlated with the differences in necrotic
      activities. This residue could be either an active or a regulatory site, involved
      in the interaction with a receptor responsible for necrosis induction.

PMID- 1368360
TI  - Characterization of bispecific caffeic acid/5-hydroxyferulic acid O
      methyltransferase from aspen.
AB  - Bispecific O-methyltransferase (OMT, EC 2.1.1.68) which catalyses the meta
      specific methylation of caffeic acid and 5-hydroxyferulic acid was purified to
      homogeneity from the developing secondary xylem of aspen (Populus tremuloides).
      The enzyme was purified by conventional techniques and affinity chromatography on
      S-adenosyl-L-homocysteine agarose using substrate elution. The enzyme has a M(r)
      of 40,000 as determined by SDS-PAGE. Amino acid sequences of three peptides
      produced from a proteolytic digest of bispecific OMT were obtained by automated
      Edman degradation. Polyclonal antibodies raised against the purified OMT reacted
      strongly to OMT in both purified and unpurified fractions in western blots.
      Addition of an equal concentration of anti-OMT IgG to crude extract protein
      inhibited OMT activity by more than 70%.

PMID- 1368361
TI  - L-asparaginase from developing seeds of Lupinus arboreus.
AB  - Asparaginase (EC 3.5.1.1) activity reached a maximum 40 days post anthesis in
      developing seeds of Lupinus arboreus and this correlated with the appearance of
      other ammonia assimilatory enzymes. Asparaginase, purified from these developing
      seeds, was resolved into three isoforms, designated asparaginases A, B and C. A
      major protein species in asparaginase A preparations co-focussed with enzyme
      activity on an isoelectric focussing gel. When analysed by SDS-PAGE, asparaginase
      isoforms A and B each yielded several polypeptides with M(r)s in the 14,000 to
      19,000 ranged. These peptides are fragmentation products of an M(r) 36,000
      asparaginase subunit. Polyclonal antibodies raised against asparaginase isoforms
      A and B precipitated asparaginase activity from a partially purified L. arboreus
      seed extract. Immunoaffinity chromatography recovered polypeptides with M(r)s
      between 14,000 and 19,000. Partial protein sequences were obtained for these
      asparaginase polypeptides.

PMID- 1368362
TI  - Biologically active labdane-type diterpene glycosides from the root-stalks of
      Gleichenia japonica.
AB  - A glycoside showing a strong growth inhibition of lettuce was isolated from the
      root-stalks of Gleichenia japonica and its structure was established to be the 3
      O-alpha-rhamnopyranosyl-(1----2)-beta-glucopyranoside of 13-O-alpha
      rhamnopyranosyl-(+)-3 beta-hydroxymanool. In addition, two related glycosides
      were also isolated and they were characterized as the 3-O-beta-fucopyranosyl-(1--
      -3)-alpha-rhamnopyranosyl-(1----2)-beta- glucopyranoside of 13-O-alpha
      rhamnopyranosyl-(+)-3 beta-hydroxymanool and the 13-O-rhamnopyranoside of the
      same diterpene alcohol. The diterpene alcohol accelerated the growth of lettuce.

PMID- 1368363
TI  - Anthocyanins from cell suspension cultures of Daucus carota.
AB  - Six anthocyanins were isolated from cell suspension cultures of an Afghan
      cultivar of Daucus carota by PC or HPLC. The structures of these compounds were
      elucidated by spectroscopic methods as cyanidin 3-O-lathyroside, cyanidin 3-O
      (2''-O-beta-D-xylopyranosyl-6''-O-beta-D-glucopyranosyl-beta-D-
      galactopyranoside), and the latter acylated with 4-coumaric, ferulic, 4
      hydroxybenzoic or sinapic acid. Unusual 1H NMR chemical shifts and 1H NOE data
      indicate an intramolecular copigmentation of the aglycone with these aromatic
      residues.

PMID- 1368364
TI  - Oleanane glycosides from Glycyrrhiza yunnanensis roots.
AB  - From the roots of Glycyrrhiza yunnanensis, collected in Yunnan, China, six new
      oleanane-type triterpene glycosides named yunganosides A1, B1, C1, D1, E2 and F2
      were isolated together with hypaphorine. The structures of these glycosides were
      established by spectroscopic and chemical means.

PMID- 1368365
TI  - Steroidal glycosides from the bulbs of Lilium dauricum.
AB  - The bulbs of Lilium dauricum yielded 11 compounds, including six new steroidal
      glycosides. The structures have been determined by spectral analysis and
      hydrolysis to be (25R,26R)-26-methoxyspirost-5-en-3 beta-ol 3-O-alpha-L
      rhamnopyranosyl-(1----2)-O-[alpha-L-arabinopyranosyl-( 1----3)]- beta-D
      glucopyranoside, (25R,26R)-26-methoxyspirost-5-en-3 beta-ol 3-O-alpha-L
      rhamnopyranosyl-(1----2)-O-[beta-D-glucopyranosyl-(1----4)]- beta-D
      glucopyranoside, (25R)-spirost-5-en-3 beta-ol (diosgenin) 3-O-alpha-L
      rhamnopyranosyl-(1----2)-O-[alpha-L-arabinopyranosyl- (1----3)]-beta-D
      glucopyranoside, (25R)-3 beta,17 alpha-dihydroxy-5 alpha-spirostan-6-one 3-O
      alpha-L-rhamnopyranosyl-(1----2)-beta-D-glucopyranoside, (25R)-3 beta, 17 alpha
      dihydroxy-5 alpha-spirostan-6-one 3-O-alpha-L-rhamnopyranosyl-(1----2)-O-[alpha-L
      arabinopyranosyl-(1----3)]-beta-D-glucopyranoside and (20R,22R)-3 beta,20,22
      trihydroxy-5 alpha-cholestan-6-one (tenuifoliol) 3-O-alpha-L-rhamnopyranosyl-(1--
      -2)-beta-D-glucopyranoside. The absolute configurations of C-20 and C-22 of
      tenuifoliol were further confirmed by detailed analysis of the NOE difference
      spectrum of the corresponding isopropylidene derivative. Several known compounds
      were also isolated and identified.

PMID- 1368366
TI  - Saponins from Trifolium repens.
AB  - From the whole plant of white clover, Trifolium repens, five new triterpenoid
      saponins, designated cloversaponins I-V, were isolated together with four known
      saponins, beta-D-glucoronopyranosylsoyasapogenol B, soyasaponin I, soyasaponin II
      and azukisaponin II as their methyl esters. Their structures were determined by
      2H NMR and 13C NMR spectroscopy and chemical evidence.

PMID- 1368368
TI  - Effect of parB on plasmid stability and gene expression in Xanthomonas
      campestris.
AB  - The stabilization locus parB was subcloned into the broad host range plasmid
      pAP2, which contains the alpha-amylase gene from Bacillus subtilis, and
      introduced into Xanthomonas campestris pv campestris and X.c.pv manihotis.
      Analysis of the stability of plasmid pAP2 (parB-) and pAP23 (parB+) showed that
      the parB locus decreased significantly the plasmid loss rate mainly by X.c.pv
      campestris. The lower efficiency of stabilization in X.c.pv manihotis was
      probably due to the incompatibility system between the native plasmids and the
      newly introduced pAP23. Although parB had conferred higher stability, it
      determined a lower rate of alpha-amylase activity even by the strain Cm where its
      stabilization rate was higher.

PMID- 1368367
TI  - Biosensors for process monitoring.
AB  - A short review about the biosensor research activities for bioprocess monitoring
      in the F.R.G. after its reunification is given. The principles of biosensor
      applications are presented. In situ sensors and sensors based on the principles
      of flow injection analysis are studied. Some applications of a four-channel
      enzyme thermistor, bio-field effect transistors, and immunoanalysis systems for
      real process monitoring are presented.

PMID- 1368369
TI  - An improved method for rapid purification of covalently closed circular plasmid
      DNA over a wide size range.
AB  - An improved method has been developed for the large-scale purification of
      covalently closed circular (CCC) plasmid DNA molecules of sizes ranging from 4.3
      to 73 kb. This protocol uses an alkaline-lysis procedure followed by acid-phenol
      extraction but with several modifications to previously reported methods. The
      principal modification is the replacement of NaCl by MgCl2 in the extraction
      buffer to improve yield and to remove chromosomal and other non-CCC plasmid DNA.
      Plasmid DNA can be purified in less than 1 h and used successfully in restriction
      enzyme analysis and cloning experiments.

PMID- 1368370
TI  - RAPD analysis of Campylobacter isolates: DNA fingerprinting without the need to
      purify DNA.
AB  - A method was developed to obtain reproducible DNA fingerprints from Campylobacter
      by PCR-based amplification, without the need to isolate total DNA. Randomly
      amplified polymorphic DNA (RAPD) profiles were generated with three randomly
      designed 10-mers, using each separately as an amplification primer. A range of C.
      jejuni serotypes could be typed by RAPD analysis. Depending on the primer, the
      analysis of RAPD profiles resulted in different levels of discrimination between
      the strains. Clear correlations were observed between results of RAPD analysis
      and serotyping. Two of the primers tested generated RAPD profiles which allowed
      discrimination of strains within given Penner and Lior serotypes.

PMID- 1368371
TI  - Is Australia competitive? The first Millis oration. February 1992.

PMID- 1368372
TI  - The evolution of regulatory systems for biotechnology.

PMID- 1368373
TI  - Ten reactions to the government inquiry report. A summary.

PMID- 1368374
TI  - GMO regulations in New Zealand for large scale fermentations.

PMID- 1368376
TI  - Progress in engineering HbA--a molecular resuscitator.

PMID- 1368375
TI  - Codon 65--unnatural success in protein biosynthesis.

PMID- 1368377
TI  - Antibody engineering--how to make useful therapeutics.

PMID- 1368378
TI  - Biopatents: a sense of order.

PMID- 1368379
TI  - Untangling biotechnology patents--when is 'obvious' not obvious?

PMID- 1368380
TI  - Comparing the glycosylation patterns of recombinant glycoproteins.
AB  - The glycosylation profile of a recombinant glycoprotein can not only
      significantly affect its therapeutic profile, but is also extremely sensitive to
      cell-culture and purification conditions. To define glycosylation patterns and to
      ensure consistency of recombinant glycoproteins among different preparations
      requires highly sensitive and reproducible analytical methods that can be used
      routinely. New strategies and instrumentation are being developed which should
      allow such analysis to be largely automated.

PMID- 1368381
TI  - Strategies for administering targeted therapeutic oligodeoxynucleotides.
AB  - Antisense or antigene DNA therapy of diseases that are due to aberrant gene
      expression is an exciting possibility. A variety of synthetic DNA derivatives has
      been applied in attempts to regulate the expression of many different genes, both
      in cell culture and in intact organisms (e.g. mice). Realistic design of human
      oligodeoxynucleotide-based therapeutic strategies requires many aspects of a
      candidate disease to be considered (including the disease prevalence, the number
      and nature of genes and mutations involved, and the tissues which must be
      targeted). For each DNA derivative intended for therapy, methods of targeting,
      modes of administration, pharmacokinetics, tissue distribution, toxicity,
      degradation and excretion must all be considered.

PMID- 1368382
TI  - Enzymatic and chemoenzymatic approaches to polymer synthesis.
AB  - The function of many specialized polymers calls for properties such as chirality
      and biodegradability. The stereo, -positional-and chemo-selectivities
      characteristic of enzymatic catalysis are highly desirable attributes for
      incorporation into strategies for synthesizing such polymers. Enzymes alone, or
      in combination with chemical synthesis (i.e. chemoenzymatic methodologies), are
      finding increased use in the synthesis of novel materials. Potential applications
      include water-absorbents, hydrogels, biodegradable materials, chiral adsorbents,
      liquid crystals and permselective membranes.

PMID- 1368383
TI  - Applications of an insoluble protein precipitation reagent.

PMID- 1368384
TI  - Conditions for cleaning and sterilizing a small tangential flow filtration system
      using a water-soluble cold sterilant.

PMID- 1368385
TI  - Endotoxin measurement: significance for the cell biology laboratory.

PMID- 1368386
TI  - Triterpenoids.
AB  - Triterpenoids isolated and characterized from various sources are reviewed. The
      newer techniques used in their isolation and structure elucidation, the newer
      skeleton triterpenoids characterized, chemical modifications and synthetic
      studies reported are discussed. A compilation of the triterpenoids isolated
      during the period 1982-1989 along with their occurrence, available physical data,
      spectroscopy and X-ray analysis used for their characterization, is included. The
      biological activities of the triterpenoids are also described.

PMID- 1368387
TI  - Arginine and lysine residues as NADH-binding sites in NADH-nitrate reductase from
      spinach.
AB  - Chemical modifications of spinach leaf nitrate reductase, and its 28,000 M(r)
      fragment with phenylglyoxal, 2,3-butanedione and pyridoxal phosphate reduce the
      catalytic activity of the enzyme. The kinetics of the modification indicate a
      rapid inactivation followed by a slower rate of inactivation. NADH-nitrate
      reductase, NADH-cytochrome c reductase and NADH-ferricyanide reductase activities
      of the nitrate reductase complex are inactivated at a faster rate when compared
      to the loss of FMNH2-nitrate reductase and reduced methyl viologen (MVH)-nitrate
      reductase activities. NADH protects the inactivation of NADH-ferricyanide
      reductase activity of the 28,000 M(r) fragment of nitrate reductase. These data
      suggest that nitrate reductase contains active sites of arginine and lysine
      residues that are involved in the NADH binding site of the enzyme.

PMID- 1368388
TI  - A gamma-pyronyl-triterpenoid saponin from Pisum sativum.
AB  - A new triterpenoid saponin was isolated from Pisum sativum and characterized as 3
      O-[alpha-L-rhamnopyranosyl-(1----2)-beta-D-galactopyranosyl(1----2)-be ta- D
      glucuronopyranosyl(1----)]-22-O-[3'-hydroxy-2'-methyl-5',6'-dihy dro-4'-
      pyrone(6'----)]-3 beta, 22 beta, 24-trihydroxyolean-12-ene. The name
      chromosaponin I is proposed. Chromosaponin I yielded soyasaponin I, known as
      phytochrome inhibitor, during extraction, but the latter was not found in the
      free form in this plant.

PMID- 1368389
TI  - A dammarane saponin from Neoalsomitra integrifoliola.
AB  - Neoalsoside A, a new dammarane saponin, was isolated from Neoalsomitra
      integrifoliola and characterized as 12 beta, 23 beta, 25-trihydroxy-(20S)(24S)
      epoxydammarane 3-O-alpha-L-rhamnosyl(1----2)-alpha -rhamnosyl(1---- 3)-beta-D
      glucoside.

PMID- 1368390
TI  - A triterpenoid saponin from Phytolacca esculenta.
AB  - A new triterpenoid saponin, 3-O-[beta-D-glucopyranosyl(1----4)-beta-D-
      xylopyranosyl]-28-O-beta-D-glucopyranosyl-30-methyloleanate-9(11), 12-dien-
      2,3,23-trihydroxyl-28-oic acid, was isolated from the roots of Phytolacca
      esculenta. The structure was assigned by chemical methods and spectral analysis
      (1H, 13C, DEPT NMR, EIMS and FABMS) including 1H-1H COSY, 1H-13C COSY and 1H-1H
      NOESY.

PMID- 1368391
TI  - Bayogenin and asterogenic acid glycosides from Bellis perennis.
AB  - Four novel triterpenoid saponins were isolated from the underground parts of
      Bellis perennis. The structures were elucidated as 3-O-beta-D-glucopyranosides of
      2 beta,3 beta,16 alpha-trihydroxyolean-12-ene-28-oic acid-28-alpha-L-
      rhamnopyranosyl(1----2)-[beta-D-glucopyranosyl(1----6)]-beta-D- glucopyranoside,
      2 beta,3 beta,23-trihydroxyolean-12-ene-28-oic acid-28-O-beta-D-xylopyranosyl (1-
      --2)-[beta-D-glucopyranosyl (1----6)]- beta-D-glucopyranoside and 2 beta,3
      beta,23-trihydroxyolean-12-ene-28-oic acid-28-O-alpha-L-rhamnopyranosyl(1----2)
      [beta-D-glucopyranosyl(1----6) ]- beta-D-glucopyranoside and as 3-O-alpha-L
      rhamnopyranosyl-2 beta,3 beta,23-trihydroxyolean-12-ene-28-oic acid-28-O-beta-D
      glucopyranosyl(1----2)-[beta-D-glucopyranosyl(1----6)]- beta-D-glucopyranoside by
      means of high field 1D and 2D NMR spectroscopic methods without recourse to
      derivatization or comparison with previous data.

PMID- 1368392
TI  - Databases of complex carbohydrates.

PMID- 1368393
TI  - Biosafety monitoring devices for biotechnology processes.

PMID- 1368394
TI  - The matrix metalloproteinases and their natural inhibitors: prospects for
      treating degenerative tissue diseases.
AB  - Uncontrolled matrix metalloproteinase activity is thought to be a cause of the
      tissue damage observed in many disease processes. None of the drugs currently in
      use can prevent tissue destruction, and strategies for the development of
      synthetic inhibitors have been hampered by a poor understanding of the
      biochemistry of matrix metalloproteinases. Recent cDNA cloning efforts and
      characterization of recombinant human matrix metalloproteinases have permitted
      structure-function analysis of the enzymes and their inhibitors. Progress in this
      area should help indicate a route to rational strategies for designing lead
      therapeutic compounds.

PMID- 1368395
TI  - Biosurfactants: moving towards industrial application.
AB  - Chemically synthesized surface-active compounds are widely used in the
      pharmaceutical, cosmetic, petroleum and food industries. However, with the
      advantages of biodegradability, and production on renewable-resource substrates,
      biosurfactants may eventually replace their chemically synthesized counterparts.
      So far, the use of biosurfactants has been limited to a few specialized
      applications because biosurfactants have been economically uncompetitive. There
      is a need to gain a greater understanding of the physiology, genetics and
      biochemistry of biosurfactant-producing strains, and to improve process
      technology to reduce production costs.

PMID- 1368396
TI  - Kinetic studies of cellular metabolic activity, specific IgG production rate, IgG
      mRNA stability and accumulation during hybridoma batch culture.
AB  - During I.13.17. hybridoma batch cultivation, the levels of cytoplasmic mRNAs
      specifying immunoglobulin heavy (H) and light (L) chains peaked during the
      exponential phase and decreased significantly during the decline phase. This
      variation was found to parallel the rate of DNA synthesis and the total
      cytoplasmic RNA content. Moreover, we have investigated the possibility that the
      stability of H- and L-chain mRNAs could account for the observed difference in
      their levels throughout the batch culture. Using a transcription inhibitor
      (actinomycin D), we found that the differential accumulation of both mRNAs
      reflected transcript stability. However, at any growth stage of the culture, the
      specific monoclonal antibody production rate (pg IgG cell-1 h-1) was not
      reflected by the levels of H- or L-chain mRNAs, but could be partially correlated
      to the specific metabolic activity of the cells.

PMID- 1368397
TI  - Increased activity and stability of poly(ethylene glycol)-modified trypsin.
AB  - The reaction of trypsin with activated monomethoxypoly(ethylene glycol) with
      various molecular masses led to the development of a series of poly(ethylene
      glycol)-modified trypsins (PEG-trypsins). On determining the catalytic properties
      of PEG-trypsin using N-benzoyl-L-arginine p-nitroanilide as a substrate, a three-
      to fourfold increase in the maximal velocity of hydrolysis was found to occur,
      whatever the size of the PEG moiety used. PEG-trypsin with higher molecular mass
      moieties showed lower Michaelis constant values. The activation of trypsin was
      neither reversed by nucleophiles such as hydroxylamine, nor prevented when
      modification was carried out in the presence of benzamidine or in the presence of
      the polypeptidic soybean trypsin inhibitor. Chemical modification of about 80% of
      the free amino groups with PEG chains significantly improved the resistance to
      heat and detergents. This might result from the formation of a highly hydrogen
      bonded structure around the enzyme.

PMID- 1368398
TI  - Immobilization of permeabilized Escherichia coli cells with penicillin acylase
      activity.
AB  - Escherichia coli cells with penicillin acylase activity were sequentially treated
      at pH 7.8 with aqueous solutions of N-cetyl-N,N,N-trimethylammonium bromide and
      glutaraldehyde and then immobilized within porous polyacrylamide beads. The
      immobilized whole cells showed enhanced hydrolysis rates in the conversion of
      benzylpenicillin to 6-aminopenicillanic acid (6-APA) compared to untreated cells
      immobilized and used under identical conditions. The immobilized system showed no
      apparent loss in enzyme activity when used repeatedly over 90 cycles for 6-APA
      production from 4% benzylpenicillin.

PMID- 1368399
TI  - Can milk replace serum in mammalian cell culture?

PMID- 1368400
TI  - Effect of purine supplementation on the growth of salmonid cell lines in
      different mammalian sera.
AB  - The Chinook salmon embryo cell line, CHSE-214, grew well in fetal bovine serum
      (FBS) but poorly in dialyzed (d) FBS. Purines restored most but not all growth
      promoting activity to dFBS, which suggests that purines account for a large
      portion of the dialyzable fraction's growth-promoting activity. CHSE-214 died in
      newborn calf serum (NCS) but grew slightly in dNCS, which suggests that the
      dialyzable fraction of NCS contains a toxic component(s). Little or no
      proliferation occurred in calf serum (CS); some took place in horse serum (HS).
      Porcine serum (PS) was very toxic. In all these sera except PS and HS, the purine
      nucleoside, inosine, significantly enhanced growth, whereas the pyrimidine
      nucleoside, uridine, was without effect. The other purines, hypoxanthine,
      adenine, adenosine and guanosine also stimulated proliferation but not as well as
      inosine. Inosine also enhanced the growth of the rainbow trout gonadal cell line,
      RTG-2. Although their morphology underwent minor alterations in medium with
      inosine, CHSE-214 cells could be grown indefinitely in CS and inosine as
      effectively as in the more expensive FBS.

PMID- 1368401
TI  - Stability of von Willebrand factor secretion in different human endothelial
      hybrid cell lines.
AB  - Endothelial cells form a highly differentiated tissue on the inner surface of
      blood vessels. One of the typical characteristics is the expression of von
      Willebrand Factor, a protein that participates in blood coagulation. The in vitro
      cultivation of endothelial cells is limited by the fact that primary cells become
      senescent after 40 generation doublings. We have immortalized human endothelial
      cells by somatic cell hybridization. Primary cells were fused to different tumor
      cell lines of murine and human origin. The degree of differentiation of the
      resulting hybrids was analyzed by characterizing the expression of von Willebrand
      Factor. This protein was identified intracellularly and in the culture
      supernatant. During long-term cultivation the hybrid cells showed a tendency to
      lose this differentiated property even after several subcloning steps. However by
      fusing them with primary endothelial cells a second time, cell lines expressing
      von Willebrand Factor for more than 180 population doublings were generated.

PMID- 1368402
TI  - Growth study of lactate and ammonia double-resistant clones of HL-60 cells.
AB  - The possibility that lactate and ammonia accumulation may have less detrimental
      effect on cell growth than usually admitted is investigated. We report here the
      isolation of several HL-60 subclones able to proliferate in the presence of 60 mM
      sodium lactate and 4 mM ammonium chloride, concentrations usually considered to
      be toxic for cell proliferation. Growth kinetics and final cell densities of
      these clones in suspension cultures were similar to the HL-60 cell population in
      control medium as well as in medium containing ammonia and lactate in which
      control cells were unable to grow. The metabolic pattern of the double-resistant
      clones revealed that lactate and ammonia formation was inhibited in the presence
      of lactate and ammonia in the medium, while alanine production and arginine
      consumption were enhanced irrespective of the medium.

PMID- 1368403
TI  - Glutamine limited fed-batch culture reduces the overflow metabolism of amino
      acids in myeloma cells.
AB  - The murine myeloma cell line Sp 2/0-Ag 14 was cultured in an ordinary batch
      culture and in a glutamine limited fed-batch culture. In batch culture, the
      overflow metabolism of glutamine ends in excess production of ammonium and the
      amino acids alanine, proline, ornithine, asparagine, glutamate, serine and
      glycine. This pattern was dramatically changed in the fed-batch culture.
      Glutamine limitation halved the cellular ammonium production and reduced the
      ratio of NH4+/glutamine. The excess production of alanine, proline and ornithine
      was reduced by a factor of 2-6 while asparagine was not produced at all. In
      contrary to the other amino acids glycine production was increased. These results
      are discussed in view of the different nature of glutamine metabolism in the
      mitochondrial compartment vs. the cytosolic. Furthermore, essential amino acids
      were used more efficiently in the fed-batch as judged by the increase in the
      cellular yield coefficients in the range of 1.3-2.6 times for seven of the 11
      consumed ones. In all, this leads to a more efficient use of the energy sources
      glucose and glutamine as revealed by an increase in the cellular yield
      coefficient for glucose by 70% and for glutamine by 61%.

PMID- 1368404
TI  - Use of fluorescence anisotropy determinations for indicating the physiological
      status of hybridoma cell cultures.
AB  - The evolution of lipid compartment fluidity during culture of hybridoma cells was
      studied by fluorescence polarization measurements. The probe partition between
      the plasma membrane and intracytoplasmic compartments was determined by a
      quenching fluorescence method. A progressive decrease of the plasma membrane
      fluidity was observed during the growth phase with an increase during stationary
      and degeneration phases of the culture. These data suggest that fluidity
      parameters could be used to follow the behaviour of hybridoma cell cultures.

PMID- 1368405
TI  - Viability measurements of hybridoma cells in suspension cultures.
AB  - Several methods were applied to determine the viability of hybridoma cells in
      suspension. These methods include dye inclusion and exclusion assays such as the
      classical trypan blue exclusion assay, the propidium iodide (PI) exclusion assay
      and the fluorescein diacetate (FDA) inclusion assay. Furthermore, the relation
      was studied between release of lactate dehydrogenase (LDH) by hybridoma cells and
      their viability. Also the ATP content of the cells and cellular heterogeneity as
      measured with a flow cytometer were determined in relation to cellular viability.
      The dye inclusion and exclusion assays using trypan blue, FDA, PI were shown to
      be useful methods to determine cellular viability. With the FDA and PI methods it
      was possible to obtain additional information about cells which are in a
      transition state between viable and non-viable. The viability according to the
      scatter properties of the cells appears to reflect the overall condition of the
      cells, although interpretation of the results is difficult. Measurement of LDH
      release in the culture fluid or the cytoplasmic ATP content could not be used as
      parameters for cell viability.

PMID- 1368407
TI  - The enhancement of specific antibody production rate in glucose- and glutamine
      controlled fed-batch culture.
AB  - The concentration effects of certain amino acids (Asp, Ile, Leu, Lys, Met, Val,
      Phe and Gln which were highly consumed during cultivation), and glucose on cell
      growth and antibody productivity were investigated using dish culture. From these
      experiments, it was found that only glutamine enrichment enhanced the specific
      antibody production rate. The other amino acids described above did not affect
      either the specific growth rate or specific antibody production rate. Thus we
      investigated the quantitative effects of glutamine concentration in the range of
      0.4-33.3 mmol.l-1 on kinetic parameters in fed-batch culture which kept both
      glucose and glutamine concentration constant. As a result the specific growth
      rate decreased with increase in glutamine concentration in the range larger than
      20 mmol.l-1. The specific antibody production rate had a maximum value at about
      25 mmol.l-1 glutamine concentration.

PMID- 1368406
TI  - The potential of flow cytometric analysis for the characterization of hybridoma
      cells in suspension cultures.
AB  - Flow cytometric (FC) analysis was applied to determine changes at cellular level
      during the cultivation of hybridoma cell line MN12 in a suspension batch culture.
      The relative cell size, cytoplasmic and membrane IgG content and the viability
      were monitored. Besides, the specificity of the cytoplasmic and membrane IgG was
      ascertained by means of a synthetic peptide containing the antigenic epitope
      recognized by the antibody. Cell size was found to increase during the
      exponential growth phase. The viability as determined by FC follows a similar
      pattern with the viability data obtained by the conventional trypan blue
      exclusion test. The relative cytoplasmic and membrane IgG contents were high
      during the exponential growth and low during stationary phase. Measurement of
      cell cycle distribution and the antibody content in the culture fluid, indicated
      that the major part of the cytoplasmic IgG is secreted by cells in the G1-phase.
      It is concluded that flow cytometry is a useful tool to characterize hybridoma
      cell lines in a suspension batch culture.

PMID- 1368408
TI  - High density culture of HeLa cells in a CelliGen perfusion system.
AB  - A hollow fiber cartridge may be used in an extraneous recycle loop to facilitate
      perfusion operation of a stirred tank bioreactor. Retention of cells while
      removing waste products and replenishment with fresh nutrients allows higher than
      normal cell densities obtained in batch or continuous culture systems. This
      system successfully propagated HeLa cells to over 11 million viable cells per
      milliliter. Much higher perfusion rates (up to 4 vessel volumes per day) were
      necessary for high density culture of HeLa cells compared to BHK or a hybridoma
      cell line because of a much higher specific cellular metabolic rate. Cell
      specific glucose consumption rate, lactate production and ammonia production
      rates are several times higher for HeLa cells. Reproducible high cell densities
      and viabilities can be repeatedly obtained after harvest and dilution of a HeLa
      cell culture by partial drainage and reconstitution in the bioreactor.

PMID- 1368409
TI  - Live attenuated vaccines for human use.
AB  - Live attenuated vaccines have been successfully used for the prevention of a
      number of viral and bacterial diseases. Several vaccine strains have been
      utilized recently as expression vectors for cloned heterologous antigens. Through
      the use of recombinant DNA technology, candidate vaccine strains and vector
      systems have been developed and are undergoing clinical evaluation.

PMID- 1368410
TI  - Environmental biotechnology.

PMID- 1368411
TI  - Biotransformation of tabersonine in cell suspension cultures of Catharanthus
      roseus.
AB  - To investigate the reactions involved in the biosynthesis of vindoline from
      tabersonine, the bioconversion products formed when the latter compound was fed
      to cell suspension cultures of Catharanthus roseus were isolated and
      characterized. Two biotransformation products of tabersonine were isolated and
      shown to be lochnericine, which is formed by epoxidation of tabersonine at
      positions 14, 15, and lochnerinine, the 11-methoxylation product of lochnericine.
      The bioconversion ratio of the main biotransformation product, lochnericine,
      reached a value of 80.6% within three days.

PMID- 1368412
TI  - Triterpenoidal saponins from Madhuca butyracea.
AB  - Two new triterpenoidal saponins, butyrosides A and B, were isolated from the
      seeds of Madhuca butyracea, along with two known saponins, Mi-saponin A and 16
      alpha-hydroxy Mi-saponin A. On the basis of chemical and spectroscopic evidence,
      the structures of butyrosides A and B were established to be 3-O-beta-D
      glucopyranosyl protobassic acid 28-O-beta-D-apiofuranosyl(1----3)-beta-D
      xylopyranosyl (----4)-alpha-L-rhamnopyranosyl(1----2)-alpha-L-arabinopyranoside
      and 3-O-beta-D-glucopyranosyl 16 alpha-hydroxy protobassic acid 28-O-beta-D
      apiofuranosyl(1----3)-beta-D-xylopyranosyl (1----4)-alpha-L-rhamnopyranosyl(1---
      2)-alpha-L-arabinopyranoside , respectively.

PMID- 1368413
TI  - Steroidal saponins from Smilax lebrunii.
AB  - Two new steroidal saponins, (25 R)-spirostan-3 beta-ol-6-one-3-O-[alpha-L
      arabinopyranosyl (1----6)]-beta-D-glucopyranoside and (25 R)-spirostan-3 beta-ol
      6-one-3-O-[beta-D-glucopyranosyl(1---4)] [alpha-L-arabinopyranosyl(1----6)]-beta
      glucopyranoside, were isolated from the rhizomes of Smilax lebrunii. Their
      structures have been established by chemical and spectral methods.

PMID- 1368414
TI  - Saponins from Steganotaenia araliacea.
AB  - Six saponins have been isolated and identified from the leaves of Steganotaenia
      araliacea. They were identified as 3-O-[beta-D-galactopyranosyl(1----2)-(beta-D
      galactopyranosyl (1----3))-beta-D-glucuronopyranosyl]-21-O-tigloyl and -21-O
      angeloyl-R1-barrigenol, 3-O-[beta-D-glucopyranosyl(1----2)-(beta-D-xylopyranosyl
      (1----3))-beta-D-glucuronopyranosyl]-21-O-tigloyl and -21-O-angeloyl-R1
      barrigenol, 3-O-[beta-D-glucopyranosyl(1----2)-(beta-D-glucopyranosyl-(1----3))
      (alp ha-L- rhamnopyranosyl(1----4))-beta-D-glucopyranosyl] steganogenin and 3-O
      [(beta-D-galactopyranosyl(1----2)-beta-D-glucuronopyranosyl]-2 8-O- beta-D
      glucopyranosyl olean-12-ene-28-oic acid. Steganogenin is a new 17,22-seco
      oleanolic acid derivative. The structures of the saponins were established by
      analysis of their 1H and 13C NMR spectra with the help of 2D-experiments and by
      Californium Plasma Desorption Mass Spectrometry.

PMID- 1368415
TI  - Cardenolides from Adonis aestivalis.
AB  - Four cardenolides were isolated for the first time from the aerial parts of
      Adonis aestivalis. The compounds were identified by spectrometry and for 3-epi
      periplogenin, helveticoside also by comparison with authentic substances. Two new
      cardenolides were structurally elucidated: strophanthidin-3-O-beta-D-digitoxosido
      alpha-L-cymarosido-be ta-D-glucoside and strophanthidin-3-O-beta-D-digitoxosido
      beta-D-digoxoside-bet a-D-diginosido-beta-D-glucoside.

PMID- 1368416
TI  - Structure-activity relationships of synthetic diosgenyl diglycosides.
AB  - The haemolytic and antifungal activities of six synthetic diosgenyl diglycosides
      and diosgenyl maltotrioside were compared with each other and with those of the
      parent glucoside. In general, the haemolytic activity of each of these glycosides
      was higher than, and the antifungal activity as strong as, that of the glucoside.
      However, both activities of the lactoside were much lower than those of the
      others.

PMID- 1368417
TI  - Immunologically active metallic ion-containing polysaccharides of Achyrocline
      satureioides.
AB  - Two homogeneous, metallic ion-containing pectic polysaccharides with mean M(r)s
      of 7600 and 15,000 were isolated from dried aerial parts of Achyrocline
      satureioides by anion exchange column chromatography on DEAE-Sepharose CL-6B and
      gel filtration column chromatography on Fractogel TSK HW-50 (S). The structures,
      as determined by methylation analysis, carboxyl reduction, and partial acid
      hydrolysis, were shown to be rhamnogalacturonans. Both pectins show a pronounced
      anticomplementary effect in vitro. The larger carbohydrate AS 4 of higher M(r)
      exerts anti-inflammatory activity and a strong enhancement of phagocytosis in
      vivo.

PMID- 1368418
TI  - Generation of lysoglyceroglycolipids in the cyanobacterium, Phormidium tenue.
AB  - Two kinds of lysoglycolipids, monogalactosyl 1-monoacylglycerol and digalactosyl
      1-monoacylglycerol were generated in the cyanobacterium, Phormidium tenue, when
      it was stored at -20 degrees for more than 1 month. By comparison of the
      compositions of fatty acid residues between monogalactosyl 1-monoacylglycerol and
      monogalactosyl diacylglycerol, digalactosyl 1-monoacylglycerol and digalactosyl
      diacylglycerol, respectively, the 1-monoacylgalactolipids were presumed to be
      formed by regioselective deacylation at the sn-1 position with subsequent acyl
      group migration from the sn-2 to the sn-1 position. In contrast, 1-monoacyl
      derivatives of sulphoquinovosyl diacylglycerol and phosphatidylglycerol, the
      other membrane lipids contained in cyanobacteria, were not formed.

PMID- 1368419
TI  - Scammonins VII and VIII, two resin glycosides from Convolvulus scammonia.
AB  - Two minor ether-soluble resin glycosides, scammonins VII and VIII, were isolated
      from Radix Scammoniae, the roots of Convolvulus scammonia. In addition to (2S)-2
      methylbutyric acid and tiglic acid, they are composed, respectively, of orizabic
      acid A and a new glycosidic acid named scammonic acid B, with similar macrocyclic
      ester structures to those of the scammonic acid A-based scammonins I-VI.
      Isolation of genuine scammonins III-V, which were previously obtained as
      peracetates, is also described.

PMID- 1368420
TI  - Flavonol glycosides from Calotropis gigantea.
AB  - Besides isolation and characterization of isorhamnetin-3-O-rutinoside,
      isorhamnetin-3-O-glucopyranoside and taraxasteryl acetate, a new flavonol
      trisaccharide was isolated from the aerial parts of Calotropis gigantea, and its
      structure was established as isorhamnetin-3-O-[2-O-beta-D-galactopyranosyl-6-O
      alpha-L-rhamnopy ranosyl]- beta-D-glucopyranoside by a combination of fast atom
      bombardment mass spectroscopy, 1H and 13C NMR spectra and some chemical
      degradations.

PMID- 1368421
TI  - Nucleotide and amino acid sequence of pap-gene (pediocin AcH production) in
      Pediococcus acidilactici H.
AB  - N-terminal analysis of purified pediocin AcH produced a partial sequence of 23
      amino acids. This sequence matched perfectly with a segment of 23 amino acids in
      a 62 amino acid molecule generated from the 186 nucleotide sequence open reading
      frame in a Hind III fragment in pSMB74 encoding pap-gene (pediocin AcH
      production). It is suggested that the molecule is translated as inactive
      prepediocin AcH of 62 amino acids. Then through enzymatic modifications the
      leader segment of 18 amino acids is removed from the NH2-terminal. The remaining
      segment of 44 amino acids is active pediocin AcH of 4628 M(r).

PMID- 1368422
TI  - The antibacterial activity of Virkon measured by colony growth and
      bioluminescence of lux recombinant Listeria monocytogenes.
AB  - Concentration exponents for the broad spectrum antimicrobial Virkon were
      determined for Listeria monocytogenes using both plate counts and bioluminescence
      measurements; the values of 3.15 and 2.6 indicate a close equivalence between
      these two measurement procedures. Virkon is an effective biocide for L.
      monocytogenes at the manufacturer's in-use concentration of 1%.

PMID- 1368423
TI  - Role of diffusion in nonaqueous enzymology. 1. Theory.
AB  - Using a set of standard equations, we have calculated the role of internal and
      external mass transfer in limiting the rate of enzyme-catalysed reactions in
      anhydrous organic solvents and supercritical fluids. We have shown that enzyme
      particles suspended in anhydrous organic solvents will be subject to increasing
      diffusional limitation as the enzyme activity and particle size increase. Using
      particle dimensions, as measured by scanning electron microscopy, we have
      prepared a series of graphs that will enable investigators to determine whether
      their combination of particle size and activity will result in internal or
      external diffusional limitations. We have shown that supercritical fluids can be
      expected to enhance the activity of enzymes in nonaqueous environments as a
      result of the high diffusivity of the bulk solvent. The plots also clearly
      indicate that enzyme particles in supercritical fluids require nearly two orders
      of magnitude less agitation than those suspended in conventional solvents in
      order to overcome any external mass transfer limitations.

PMID- 1368424
TI  - Electrochemical enzyme immunoassay for detection of toxic substances.
AB  - Sensors that provide reliable, rapid measurement of toxic substances are needed
      to solve significant human health and safety problems. We developed a new
      biosensor design that combines the advantages of immunoassay with electrochemical
      response. We established that this enzyme-linked immunosensor measures toxic
      substances in biological samples. The biosensor consists of two major elements:
      (1) an electrical conducting layer having immobilized enzyme, polyclonal or
      monoclonal antibodies, and other necessary reagents, and (2) the electronic
      components used in the signal readout. The result is an amperometric immunoassay
      based on coupling the immunochemical reaction to the enzyme electrode response by
      using a soluble, electrochemically active mediator. The specific question
      addressed was: Does the system's immunochemical detection reliably respond at
      sufficiently low analyte concentrations? We present our results in these areas:
      (1) enzyme immobilization on colloidal gold; (2) colloidal gold-enzyme deposition
      on the electrode surface; (3) mediator-antigen conjugate synthesis; (4) antibody
      incorporation at the electrode surface; (5) bioelectrode characterization and
      optimization; and (6) immunosensor demonstration to detect antigen. Sensors that
      employ immunochemical detection will have broad applicability to detect/diagnose
      toxic substances in biological samples such as blood and urine and in
      environmental samples such as wastewater and drinking water.

PMID- 1368425
TI  - Colorimetric determination of free and total cholesterol by flow injection
      analysis with a fiber optic detector.
AB  - A flow injection method for the determination of total and free cholesterol is
      presented. Cholesterol esterase and cholesterol oxidase are immobilized on
      aminoalkyl glass beads. The beads are packed into a tubular glass reactor. The
      cholesterol esters traversing through the esterase reactor are cleaved to
      cholesterol and fatty acids. The oxidase reactor converts cholesterol to cholest
      4-en-3-one and hydrogen peroxide is generated. The sample stream is merged with
      reagent streams consisting of a peroxidase solution and a solution of 2,2'-azino
      bis-(3-ethyl-benzthiazoline-6-sulfonic acid) diammonium salt, and a hydrogen
      peroxide-dependent color reaction takes place in a short coiled reactor. The
      signal is monitored by means of fiber optic instrumentation. Cholesterol
      concentration can be related to the absorption of the oxidized dye form at a
      wavelength of 425 nm. The working range is 0.5-0.8 mmol l-1, and the sample
      throughputs are 60 and 30 h-1 for free and total cholesterol, respectively.

PMID- 1368426
TI  - High-density Escherichia coli cultivation process for hyperexpression of
      recombinant porcine growth hormone.
AB  - Fermentation studies were performed on an Escherichia coli culture that carries a
      recombinant plasmid composed of an ampicillin-resistant gene, a temperature
      regulated pL promoter, and a porcine pituitary cDNA sequence coding for growth
      hormone. The objective was to achieve high cell density while maintaining the
      specific expression level of recombinant porcine growth hormone (r-pGH) observed
      in shake flasks. At a specific expression level of 20% of total cell protein, the
      cell density of a glucose-limited fed-batch process reached 38 units of OD600 in
      14 h, compared to flask cultivation, which resulted in only 1.4 units of OD600 in
      the same period. The observed critical fermentation conditions for maximal
      expression included (1) limiting glucose concentration below 1 g l-1 throughout
      the fed-batch growth and induction phases, (2) keeping postinduction temperature
      at 42 degrees C for 5-7 h, and (3) maintaining a postinduction growth rate around
      0.17-0.21 h-1.

PMID- 1368427
TI  - Testing and evaluation of off-gas filters for bioreactors by a new bacterial
      aerosol challenge test method (TBAC).
AB  - A TNO bacterial aerosol challenge (TBAC) filter test rig was developed for direct
      assessment of the effectiveness of bioreactor off-gas filters as an alternative
      to routinely applied indirect wet integrity testing (IT). This TBAC test rig is
      based on bacterial aerosol challenging with Pseudomonas diminuta and dual
      monitoring by laser particle counting (LPC) and Andersen microbial sampling (AMS)
      of viable cells. The TBAC filter test rig is able to reproduce the various
      conditions encountered in fermentation processes. In experiments with several
      filters from one class, it was demonstrated that some filters were actually
      penetrated by up to 3,000 viable cells per test, despite their approval by
      commercially available IT test equipment. Repetitive filter use, prolonged use,
      and autoclaving of filters resulted in an increase in pressure drop over the
      filter but improved the performance of leaking/deviant filters due to building up
      of a filter cake (this phenomenon was identified by electron microscopy). The
      integrity tests used were found inadequate for accurate assessment of filter
      quality. Certification of filter lots by random tests of commercially available
      off-gas filters using sensitive direct methods such as those presented here might
      be advisable, as not all filters purchased were of appropriate quality.

PMID- 1368428
TI  - Influence of solvent and water activity on kinetically controlled peptide
      synthesis.
AB  - alpha-Chymotrypsin deposited on Celite was used to catalyse peptide synthesis
      reactions between N-protected amino acid esters and leucine amide in organic
      media with low water content. The influence of the solvent and the thermodynamic
      water activity on the reaction kinetics was studied. The substrate specificity in
      the reactions was shown to be a combination of the substrate specificity of the
      enzyme in aqueous media and the influence of the solvents. The magnitude of the
      solvent effects differed greatly depending on the substrates used. In hydrophobic
      solvents high reaction rates were observed and the competing hydrolysis of the
      ester substrate occurred to only a minor extent. Reactions occurred at water
      activities as low as 0.11, but the rate constants increased with increasing water
      activity and were about two orders of magnitude higher at the highest water
      activity tested (0.97).

PMID- 1368429
TI  - Diffusion of proteases in calcium alginate beads.
AB  - Diffusion of proteases from Bacillus subtilis and Serratia marcescens within
      calcium alginate beads has been assayed, and the experimental data fitted into a
      mathematical model for diffusion into a finite volume liquid medium. Values of
      effective diffusivity were calculated for the studied proteases and compared with
      the available data in the literature for molecules of lower molecular weight.

PMID- 1368430
TI  - Optimization of animal and plant cell dependent bioprocesses. Report on the
      Animal and Plant Cell Culture Technology Working Party of the European Federation
      of Biotechnology. 2-3 December 1991, Place Hotel do Guincho, Cascais, Portugal.

PMID- 1368431
TI  - Protein engineering.

PMID- 1368432
TI  - NMR structures and methodology.

PMID- 1368433
TI  - Structural consequences of mutation.
AB  - The way a protein responds to mutation provides key insights into its
      architecture and energetics. Mutations are improving the understanding both of
      protein folding and stability, and of the adaptability of the hydrophobic core.
      The importance of intermolecular effects in crystal structures is being
      emphasized and new insights into the correspondence between crystal and solution
      structures are being developed.

PMID- 1368434
TI  - Structure prediction and modelling.
AB  - Cracking the second fundamental code of molecular biology (how the tertiary
      structure of a protein is determined by its amino acid sequence) remains an
      elusive goal. However, the impetus to establish credible approximations, if not a
      definitive solution to this relationship, has never been greater. In the past
      year significant progress has been made through a series of novel approaches.
      This review describes the most important developments and outlines how they can
      be usefully employed by those whose specialization lies outside the field.

PMID- 1368435
TI  - New recombinant DNA methodology for protein engineering.
AB  - Over the past year considerable progress has been made in the application of
      recombinant DNA technology to protein engineering. A number of new methods for
      gene synthesis and mutagenesis have been reported that simplify the construction
      of novel coding sequences. The polymerase chain reaction plays an increasingly
      important role in these methods. Amino acid diversity has been extended by the
      incorporation of unnatural amino acids via coupled in vitro transcription
      translation methods. Novel random mutagenesis strategies have been developed that
      substitute amino acids with a desired chemical character at a given position,
      thereby generating a sophisticated library of protein variants.

PMID- 1368436
TI  - Rapid evolution of peptide and protein binding properties in vitro.
AB  - A significant bottleneck in protein engineering arises from the problem of
      identifying particular molecules with new functions from a potentially enormous
      range of peptide or protein variants. Two areas of emerging technology, phage
      display and multiple peptide synthesis, provide new means of screening huge
      libraries in vitro for novel binding properties. This review is also published in
      Current Opinion in Structural Biology 1992, 2:597-604.

PMID- 1368437
TI  - Fusion proteins in biotechnology.
AB  - Gene fusion techniques allow the production of recombinant proteins featuring the
      combined characteristics of the parental products. Originally, these techniques
      were used to probe transcriptional and translational activity, to translocate
      proteins across cell membranes, and to facilitate the recovery of proteins.
      Recently, new applications have emerged in areas such as protein refolding,
      immunology, drug targeting and protein display. A slightly modified version of
      this review is also published in Current Opinion in Structural Biology 1992,
      2:569-575.

PMID- 1368438
TI  - Alteration of enzyme specificity and catalysis.
AB  - In the past year, site-directed mutagenesis and other forms of protein
      engineering have been used to reverse the substrate specificity of several pairs
      of enzymes, including disulphide oxidoreductases, proteases, sugar-processing
      enzymes, and nucleases, as well as the specificity of hormones and their
      receptors. Mutations have been found that affect rate-determining steps, allowing
      normally transient intermediates to accumulate. Other mutations endow enzymes
      with totally new chemical reactions, and even novel biological functions. A
      combination of molecular genetics and chemical modification has been used for
      protein engineering.

PMID- 1368439
TI  - Protein metal-binding sites.
AB  - Metal ions have a role in a variety of important functions in proteins including
      protein folding, assembly, stability, conformational change, and catalysis. The
      presence or absence of a given metal ion is crucial to the conformation or
      activity of over one third of all proteins. Recent developments have been made in
      the understanding and design of metal-binding sites in proteins, an important and
      rapidly advancing area of protein engineering.

PMID- 1368440
TI  - Protein engineering for molecular electronics.
AB  - Recombinant DNA technology allows the manipulation of the physical properties of
      proteins that perform electron transport and photochemical processes. Recent work
      is reviewed that has a potential impact on the development of molecular
      electronic devices, within a general framework outlining strategies for device
      fabrication. This review is also published in Current Opinion in Structural
      Biology 1992, 2:587-592.

PMID- 1368441
TI  - Antibody engineering.
AB  - Current research into antibody engineering stresses the design of constructs that
      have both scientific and medical significance. Highlights of the past year
      include several successful humanizations of non-human antibodies, in which a
      human antibody is created that possesses the same binding specificity as the non
      human one, and phage display of antibodies. This review is also published in
      Current Opinion in Structural Biology 1992, 2:593-596.

PMID- 1368442
TI  - Serpins: implications of a mobile reactive centre.
AB  - The serpins are unique among the families of serine proteinase inhibitors in
      having a reactive centre that is situated on a mobile loop. The structures of
      three alternative conformations are now known, and it can be deduced that the
      active form involves the partial insertion of the loop into the A sheet of the
      molecule. The ability of the loop to move in and out of this sheet has been
      adapted by evolution to allow the modulation of inhibitory activity. Manipulation
      of the structure of the loop and of other functional domains in the serpin
      superfamily enables the production of serpins with tailor-made activities. The
      ability of the loop to lock in latent conformations or to take part in
      intermolecular polymerization has implications for the production and
      stabilization of recombinant serpins. This review has been adapted from Current
      Opinion in Structural Biology 1992, 2:438-446.

PMID- 1368443
TI  - Cytotoxic proteins.
AB  - Cytotoxic proteins, which enter eukaryotic cells and catalytically inactivate
      protein synthesis, are being increasingly studied using a combination of
      molecular biology, cell biology and structural approaches. The creation of
      genetically engineered fusions with alternative cell-binding ligands paves the
      way for tailor-made, cell-type-specific killing agents.

PMID- 1368444
TI  - Protein engineering.

PMID- 1368445
TI  - Separations with dialysis and ultrafiltration: theoretical and practical
      considerations.

PMID- 1368446
TI  - Automated microfractionation of small centrifuge tubes: applications in
      analytical and preparative ultracentrifugation.

PMID- 1368447
TI  - Classification of mycobacteria by HPLC and pattern recognition.

PMID- 1368448
TI  - New technology for protein sequencing.

PMID- 1368449
TI  - Designing enzymes for use in organic solvents.
AB  - Enzymes are routinely used in organic solvents where numerous reactions of
      interest to synthetic and polymer chemists can be performed with high
      selectivity. Recently, it has become apparent that the catalytic properties of an
      enzyme can be tailored to a specific catalytic requirement by the use of solvent
      and protein engineering. The former involves altering the polarity,
      hydrophobicity, water content, etc., of the organic milieu, while the later
      applies site-directed mutagenesis to alter the physicochemical properties of the
      biocatalyst. The dominant effects of organic solvents on enzyme structure and
      function, and the potential of solvent and protein engineering to design enzymes
      to function optimally in organic media, are the major foci of this review.

PMID- 1368450
TI  - Use of monoclonal anti-enzyme antibodies for analytical purposes.
AB  - This review discusses the analytical applications of monoclonal antibodies
      specific for enzymes. One important, but not well-studied, application of these
      monoclonal antibodies is their use in immobilizing enzymes on solid supports.
      This method is based on binding the enzymes to an immobilized antibody through
      the antigen binding site of the antibody. Enzymes immobilized this way retain
      much of their activity. The utility of immobilized enzyme reactors prepared by
      immobilizing the enzymes through antibodies is demonstrated by using them in the
      determination of acetylcholine and choline in brain tissue extracts. Currently
      available methods for immobilizing antibodies and enzymes are reviewed. Other
      issues discussed in this review include the problems and advantages of
      immobilized enzyme reactors, especially when used in conjunction with HPLC. In
      addition, the applications of monoclonal antibodies for the detection and
      measurement of enzymes and their isoforms are summarized.

PMID- 1368451
TI  - Modeling transport processes in sterilization-in-place.
AB  - SIP (sterilization-in-place) of equipment using saturated steam is limited by
      transport processes that restrict the distribution of sterilizing steam. The
      following are two crucial operations: the removal of air prior to sterilization,
      and the removal of condensate during the sterilization. Using simple model
      systems of pipes and tanks, characteristic operating parameters were examined and
      steady-state models were analyzed. The results were used to evaluate design
      aspects of SIP, including heat insulation, spacing of steam traps, sloping of
      lines, steam velocities and consumption, placement of temperature sensors, and
      scale factors in piping. A more reliable SIP design is achievable by insulating
      equipment, spacing steam traps to limit condensate buildup, providing an
      effective air removal operation, and providing reliable, high-quality steam.

PMID- 1368452
TI  - Effect of oxygen supply on the suspension culture of genetically modified tobacco
      cells.
AB  - The effect of oxygen supply on the cultivation of the genetically modified
      tobacco cells and the formation of a foreign protein, beta-glucuronidase (GUS),
      was investigated in 250-mL Erlenmeyer flasks, a 5-L stirred tank fermenter, and a
      7-L air-lift fermenter. The oxygen supply was varied by using different volumes
      of medium in the case of the 250-mL Erlenmeyer flask culture or by the different
      aeration rate in the case of the two types of fermenters tested. Higher oxygen
      supply stimulated cell growth and increased oxygen consumption rate, the level of
      phenolics, and GUS productions.

PMID- 1368453
TI  - A model for beta-galactosidase production with a recombinant yeast Saccharomyces
      cerevisiae in fed-batch culture.
AB  - An unstructured model is developed to describe the growth and product formation
      behavior of a recombinant yeast Saccharomyces cerevisiae using beta-galactosidase
      as a model protein. The model shows good agreement with the experimental data
      over a range of conditions. It also accurately predicts the effect of growth rate
      on yield coefficient and gene expression. The simplicity and accuracy of the
      model make it suitable for designing and implementing control and optimization
      strategies for the production of recombinant proteins at large scale.

PMID- 1368454
TI  - An anionic galactomannan polysaccharide gum from a newly-isolated lactose
      utilizing bacterium. I. Strain description and gum characterization.
AB  - As part of an effort to obtain microorganisms able to produce polysaccharide gums
      from whey and whey permeate, soil samples from farm fields regularly treated with
      whey were screened for bacteria able to produce gums from lactose. The most
      promising organism isolated (ATCC 55046) is a facultative anaerobe, tentatively
      identified as a new Erwinia species on the basis of biochemical and morphological
      tests. The organism produces a polysaccharide gum from lactose and other sugars
      (herein named lactan gum) composed of mannose, galactose, and galacturonic acid
      with an approximate molar ratio of 5:3:2 and containing no organic acid modifying
      groups. The weight average molecular weight of the gum is approximately 7 x
      10(6). Aqueous solutions of lactan gum exhibit shear-thinning and elastic flow
      behavior with an estimated power law model flow index of 0.26 at 1% (w/w) gum.
      The viscosity of aqueous 1% (w/w) lactan gum solutions is stable over a pH range
      of 2-11, being particularly stable in alkaline environments. Aqueous 1% (w/w) gum
      solutions at pH 5-11 show excellent thermostability, retaining at least 80% of
      the original viscosity after being heated to 121 degrees C for 15 min. These flow
      properties indicate potential industrial applications in food and nonfood
      products requiring a moderate degree of thickening, wet-end additives and coating
      agents for paper products, ceramics, detergents, and binders for building
      materials.

PMID- 1368455
TI  - Escherichia coli host cell modifications in continuous culture affecting
      heterologous protein overproduction: a population dynamics study.
AB  - There are many published studies of plasmid segregational instability in
      Escherichia coli in the literature. However, the formation of plasmid-free
      segregants can be controlled by the addition of selective chemical agents like
      antibiotics. This solution has become commonplace in both the laboratory and
      industry. On the other hand, host cell modifications, which result in low
      production of plasmid-encoded protein and lead to loss of culture productivity,
      have not been adequately addressed. Continuous culture of an inducible (ptac)
      Escherichia coli vector containing strain, RB791(pKN), was characterized by
      strong dynamic changes in the cell population and product (beta-lactamase)
      expression. Long-term cultivation resulted in the loss of high-level production
      of beta-lactamase. Loss of productivity was not due to the formation of plasmid
      free cells or structural modifications to the plasmid; instead, continuous
      operation resulted in a culture dominated by irreversibly altered, low-producing
      cells. Two distinct classes of lac- mutants which inhibited induction were
      identified (Y- and I(s)).

PMID- 1368456
TI  - Production and purification of a recombinant elastomeric polypeptide, G-(VPGVG)19
      VPGV, from Escherichia coli.
AB  - An elastomeric polypeptide was produced, with the sequence G-(VPGVG)19-VPGV, as a
      fusion to glutathione S-transferase using the vector pGEX-3X. The fusion protein
      was expressed to high levels in Escherichia coli as indicated by SDS-PAGE
      analysis of induced cells. The fusion protein was affinity purified and cleaved
      with protease factor Xa, and the elastomeric polypeptide was recovered to a high
      degree of purity as indicated by SDS-PAGE followed by staining with CuCl2. The
      physical characterizations of carbon-13 and proton nuclear magnetic resonance and
      of the temperature profile for turbidity formation for the inverse temperature
      transition of hydrophobic folding and assembly attest to the successful microbial
      synthesis of the polypentapeptide of elastin. The results of these studies
      provide the initial progress toward achieving a more economical and practical
      means of producing material for elastic protein-based polymer research and
      applications.

PMID- 1368457
TI  - Monitoring intracellular protein profiles with two-dimensional gel
      electrophoresis.
AB  - Two-dimensional polyacrylamide gel electrophoresis (2D PAGE) is a method of
      separating complex protein mixtures, such as whole cell extracts, on the basis of
      protein isoelectric point and molecular weight. In bioprocess engineering,
      conventional 2D PAGE has tremendous potential to yield detailed information on
      the intracellular effect of various process conditions. It has been used in our
      work to examine global intracellular changes occurring in a typical cycloheximide
      fermentation and to look at the feedback regulatory behavior of cycloheximide
      biosynthesis. Application of the technique for bioprocess monitoring will require
      that the time necessary for preparation of a 2D electropherogram be substantially
      shortened. This may be accomplished by performing the separation on a miniature
      scale or eventually by use of capillary electrophoresis for one or more of the
      separations. Advantages and disadvantages of these two approaches are discussed.

PMID- 1368458
TI  - Immuno- and flow cytometric analytical methods for biotechnological research and
      process monitoring.
AB  - In this article, the applications of immunoanalysis and flow cytometry for
      research and process monitoring in biotechnology are discussed. Brief reviews of
      the two analytical methods are followed by descriptions of actual applications in
      various areas of biotechnology. In the case of immunoanalysis, emphasis is placed
      on systems for on-line bioprocess monitoring, and examples are given for a
      thermostable pullulanase, a mouse IgG, and antithrombin III. Although flow
      cytometry is not currently an on-line analytical technique, its value as an off
      line method is illustrated by examples of the measurement of shear stress
      effects, lipid content, and sterol content.

PMID- 1368459
TI  - Advanced methods for bioreactor characterization.
AB  - Bioreactors are characterized by the transport capacities they provide to
      optimally supply the microorganisms during production process. The transport is
      performed by flows induced in their cultivation media. In order to understand the
      extremely complex mixing, mass and heat transfer phenomena encountered, and to
      perceive their influences on bioreactor performance, sophisticated measuring
      techniques are required. This review compiles the developments currently in
      progress to surmount today's shortage of reliable measuring techniques. Measuring
      techniques are distinguished which can be used on different scales and their
      application spectra are illustrated by recently obtained results. Several new
      measuring techniques, which can be employed to resolve the flow structures, are
      discussed in detail. Only those techniques are considered which can be used to
      advantage during real cultivations in industrial-scale reactors.

PMID- 1368460
TI  - Enhancing bioprocess operability with generic software sensors.
AB  - This paper discusses the concept of generic model-based software sensors with
      particular reference to bioprocess application. The industrial need for software
      sensing is considered and two industrial bioprocess systems are used in order to
      highlight the operability problems which warrant their development. Alternative
      philosophies for formulation are considered and the relative merits of the
      methodologies discussed. In particular, two different procedures are presented-
      an adaptive linear model based method, and a method based upon artificial neural
      networks. The performances of these alternative approaches are studied by their
      application to two industrial demonstrator processes. The results serve to
      highlight the operability improvements that can be gained through software sensor
      development.

PMID- 1368461
TI  - On-line measurement in biotechnology: techniques.
AB  - Bioprocesses are generally ill controlled. This is due to the fact that the
      measurement of relevant variables is difficult. Therefore, fundamental knowledge
      of metabolic interrelations is, at least in vivo, limited. In this article, some
      of the most important measurement techniques are reviewed in order to provide an
      evaluation of their current state. Emphasis is given to the underlying principles
      and on-line capability which allow to judge their importance and potential for
      exploitation resulting in well (maybe entirely) controlled bioprocesses in the
      future.

PMID- 1368463
TI  - On-line measurement in biotechnology: exploitation, objectives and benefits.
AB  - Sound data biologically relevant are prerequisites when developing high
      performance bioprocesses. Understanding of physiological regulation as well as
      sophisticated control strategies are highly dependent on the observability of the
      culture, i.e. the generation and exploitation of suited signals even under
      complex environmental measurement conditions. Against this background, the
      increasing number of analytical systems is very supportive and, accordingly, an
      appropriate handling of sensors and measured data is of decisive importance. This
      article reports on practical experience with routines for maintenance, service
      and calibration of hardware sensors which improve the quality of measurements
      significantly. Verification and validation of signals is outlined in order to
      make the value of data exploitation tools obvious. A method for the
      characterization of information is introduced by practical examples of
      Saccharomyces cerevisiae cultures when explaining the specific properties of
      extracting biological information from raw data. Finally, examples for
      advantageous exploitation of on-line data are given.

PMID- 1368462
TI  - Biomass determination.
AB  - The reasons for and historical backgrounds of biomass determination are discussed
      under the aspects of theoretical and practical importance, usefulness and
      representativity. Off-line methods are evaluated and compared with on-line
      methods; constraints of applications and conclusiveness of results are rated.
      Special emphasis is given to the fact that mere knowledge of a bio-mass
      concentration is not sufficiently valuable to learn more about physiology nor to
      determine the effectiveness of a biotechnological process. A combination of
      several different alternative measuring principles in parallel as well as the
      exploitation of software sensors is proposed as a promising future solution.

PMID- 1368464
TI  - Flow injection analysis and in-line biosensors for bioprocess control: a
      comparison.
AB  - Miniaturization will unify the different approaches chosen for the application of
      biosensors in bioprocess control. The most versatile system, which in our opinion
      is flow injection analysis will be the method of choice for the introduction of
      biosensors in bioprocess control. A lot of experience will be gained for the
      future development of miniaturized total chemical analysis systems.

PMID- 1368465
TI  - Present and potential applications of mass spectrometry for bioprocess research
      and control.
AB  - For on-line monitoring of bioprocesses present applications are mainly restricted
      to gas analysis, but several techniques have been improved recently: membrane
      probes, the application of MS/MS techniques, methods of correlating available on
      line data like gas reaction rates with bioprocess characteristics using
      stoichiometric models and other empirical correlations. New ionization and ion
      separation methods for biomolecules are developing dramatically. Most striking
      developments in this area are improved desorption techniques, electrospray, the
      renaissance of time-of-flight instruments and new challenges in ion trap
      techniques. Enormous progress is made in the analysis of peptides and other
      biopolymers. Combinations with new separation techniques like capillary
      electrophoresis and capillary HPLC show new horizons in biomolecule analysis.

PMID- 1368466
TI  - Scale-up and optimization of culture conditions of a human heterohybridoma
      producing serotype-specific antibodies to Pseudomonas aeruginosa.
AB  - Three different stirred bioreactors of 0.5 to 121 volume were used to scale up
      the production of a human monoclonal antibody. Inoculation density and stirrer
      speed were evaluated in batch cultures, whereas dilution rate and pH were
      optimized in chemostat cultures with respect to high specific antibody production
      rate and high antibody yield per time and reactor volume. The cell line used for
      the experiments was a heterohybridoma, producing immunoglobulin M (IgM) against
      lipopolysaccharide of Pseudomonas aeruginosa. Cells were cultured in spinner
      flasks of 500 ml liquid volume for adaptation to stirred culture conditions.
      Subsequently cells were transferred to the 1.5-l KLF 2000 bioreactor and to the
      12-l NLF 22 bioreactor for pilot-scale cultures. Chemostat experiments were done
      in the 1.5-l KLF bioreactor. Cell density, viability, glucose and lactate and
      antibody concentration were measured during culture experiments. In batch
      cultures in all three stirred bioreactors, comparable maximal cell densities and
      specific growth rates were achieved. Chemostat experiments showed that at a pH of
      6.9 and a dilution rate of 0.57 per day the specific antibody production rate was
      threefold higher than similar experiments done at pH 7.2 with a dilution rate of
      0.36 per day. By optimizing pH and dilution rate in chemostat cultures the daily
      yield of human IgM increased nearly threefold from 6 to 16 mg/day and per litre
      of reactor volume. The yield per litre of medium increased twofold.

PMID- 1368467
TI  - Bovine colostrum fraction as a serum substitute for the cultivation of mouse
      hybridomas.
AB  - Fractions of bovine colostrum were prepared and their ability to support the
      growth of mouse-mouse hybridomas in culture was tested. Whey was prepared from
      defatted colostrum by removal of casein using acid precipitation. An
      ultrafiltrate was obtained from cleared whey by filtration through membranes with
      a nominal molecular mass cut-off of 100,000 Da. Colostrum ultrafiltrate contained
      1.16 milligrams protein, 0.24 milligrams immunoglobulin G (IgG) and less than
      0.24 EU (endotoxin unit)/ml endotoxins. The effect of defatted colostrum, whey
      and ultrafiltrate as serum substitutes was examined by cultivation of hybridoma
      cells in minimal essential medium containing different concentrations of the
      supplements. Under optimal conditions in ultrafiltrate-supplemented medium, the
      maximal cell concentration was 35-40% of that obtained using 10% foetal bovine
      serum, and IgG production per cell was equal to that achieved using serum. In 1%
      defatted colostrum the maximum hybridoma concentration was about 30% of that in
      10% serum, but at higher concentrations hybridoma growth was significantly
      reduced. The growth-promoting activity of whey was low. The results show that
      bovine colostrum ultrafiltrate provides a very attractive alternative to serum
      for production of monoclonal antibodies.

PMID- 1368468
TI  - Biological decomposition of dichloromethane from a chemical process effluent.
AB  - The application of specialized microorganisms to treat dichloromethane (DM)
      containing process effluents was studied. An aerobic fluidized bed reactor with a
      working volume of 801 filled with sand particles as carriers for the bacteria was
      used. Oxygen was introduced into the recycle stream by an injector device. DM was
      monitored semi-continuously. A processor controlled the feed volume according to
      the DM effluent concentration. Mineralization rates of 12 kg DM/m3bioreactor.d
      were reached within about three weeks using synthetic wastewater containing 2000
      mg/l DM as single carbon compound. DM from process water of a pharmaceutical
      plant was reduced from about 2000 mg/l in the feed to below 1 mg/l in the
      effluent at volumetric loading rates of 3 to 4 kg DM/m3bioreactor.d. Degradation
      of wastewater components like acetone and isopropanol were favoured, thus making
      the process less attractive for waste streams containing high amounts of DOC
      other than of DM. DM concentrations of up to 1000 mg/l were tolerated by the
      immobilized microorganisms and did not influence their DM degradation capacity.
      The ability to mineralize DM was lost when no DM was fed to the reactor for 10
      days.

PMID- 1368469
TI  - Oxygen-dependent desulphation of monomethyl sulphate by Agrobacterium sp. M3C.
AB  - Agrobacterium sp. M3C, previously isolated from canal-water for its ability to
      grow on monomethyl sulphate, degraded this ester with stoichiometric liberation
      of inorganic sulphate. In contrast with the biodegradation of monomethyl sulphate
      in Hyphomicrobium sp., and of other longer-chain alkyl sulphates in Pseudomonas
      spp., the pathway in Agrobacterium appeared not to involve a sulphatase enzyme
      capable of catalysing ester-bond hydrolysis. No such sulphatase was detectable
      under a range of conditions of bacterial culture, or using various methods for
      preparing cell-extracts, or different assay conditions. There was no
      incorporation of 18O-label from H2(18O) into the liberated inorganic sulphate. No
      methanol was detectable during biodegradation, and the organism was incapable of
      growth on methanol, and did not produce methanol dehydrogenase activity when
      grown on monomethyl sulphate. Tracer studies using mono[14C]-methyl sulphate
      indicated that formate serine and glycine were produced during the
      biodegradation. The presence of these amino acids, together with high activity of
      hydroxypyruvate reductase, indicated the operation of the serine pathway common
      in methylotrophs. Use of an oxygen electrode in conjunction with
      monomethyl[35S]sulphate showed that release of 35SO2(-4) was dependent on
      availability of O2, and that there was equimolar stoichiometry among monomethyl
      sulphate degraded, O2 consumed and 35SO2(-4) released. A proposed pathway for the
      degradation involved an initial mono-oxygenation to methanediol monosulphate with
      subsequent elimination of SO2(-4) and concomitant formation of formaldehyde. The
      pathway was compared with degradation mechanisms for other C1 compounds and for
      other sulphate esters.

PMID- 1368470
TI  - Enzymes involved in anaerobic degradation of acetone by a denitrifying bacterium.
AB  - The pathway of anaerobic acetone degradation by the denitrifying bacterial strain
      BunN was studied by enzyme measurements in extracts of anaerobic acetone-grown
      cells. An ADP- and MgCl2-dependent decarboxylation of acetoacetate was detected
      which could not be found in cell-free extracts of acetate-grown cells. It is
      concluded that free acetoacetate is formed by ATP-dependent carboxylation of
      acetone. Acetoacetate was converted into its coenzyme A ester by succinyl-CoA:
      acetoacetate CoA transferase, and cleaved by a thiolase into acetyl-CoA. The
      acetyl residue was completely oxidized in the citric acid cycle. The ADP
      dependent decarboxylation of acetoacetate was inhibited by EDTA, but not by
      avidin. High myokinase activities led to equilibrium amounts of ATP, ADP, and AMP
      in the reaction mixtures, and prevented determination of the decarboxylase
      reaction stoichiometry, therefore.

PMID- 1368471
TI  - Reductive dechlorination of 1,2-dichloroethane and chloroethane by cell
      suspensions of methanogenic bacteria.
AB  - Concentrated cell suspensions of methanogenic bacteria reductively dechlorinated
      1,2-dichloroethane via two reaction-mechanisms: a dihalo-elimination yielding
      ethylene and two hydrogenolysis reactions yielding chloroethane and ethane,
      consecutively. The transformation of chloroethane to ethane was inhibited by 1,2
      dichloroethane. Stimulation of methanogenesis caused an increase in the amount of
      dechlorination products formed, whereas the opposite was found when methane
      formation was inhibited. Cells of Methanosarcina barkeri grown on H2/CO2
      converted 1,2-dichloroethane and chloroethane at higher rates than acetate or
      methanol grown cells.

PMID- 1368472
TI  - Degradation of 2,4,5-trichlorophenoxyacetic acid by a Nocardioides simplex
      culture.
AB  - A Nocardioides simplex strain 3E was isolated which totally dechlorinated 2,4,5
      trichlorophenoxyacetic acid and was capable of its utilization as the sole source
      of carbon. The mechanism of 2,4,5-trichlorophenoxyacetic acid degradation by this
      strain was investigated. Chloroaromatic metabolites that occur in the lag,
      exponential and stationary growth phases of the strain Nocardioides simplex 3E
      were isolated and identified bases on a combination of TLC, GC-MS and HPLC data.
      Decomposition of 2,4,5-trichlorophenoxyacetic acid at the initial stage was shown
      to proceed by two pathways: via the splitting of the two-carbon fragment to yield
      2,4,5-trichlorophenol and the reductive dechlorination to produce 2,4
      dichlorophenoxyacetic acid. Hydrolytic dechlorination of 2,4,5
      trichlorophenoxyacetic acid was found to yield dichlorohydroxyphenoxyacetic acid,
      thus pointing to the possible existence of a third branch at the initial stage of
      degradation of the xenobiotic. 2,4,5-Trichlorophenol and 2,4
      dichlorophenoxyacetic acid produced during the metabolism of 2,4,5
      trichlorophenoxyacetic acid and in experiments with resting cells are utilized by
      the strain Nocardioides simplex 3E as growth substrates.

PMID- 1368473
TI  - Identification of metabolites from degradation of naphthalene by a Mycobacterium
      sp.
AB  - A Mycobacterium sp. isolated from oil-contaminated sediments was previously shown
      to mineralize 55% of the added naphthalene to carbon dioxide after 7 days of
      incubation. In this paper, we report the initial steps of the degradation of
      naphthalene by a Mycobacterium sp. as determined by isolation of metabolites and
      incorporation of oxygen from 18O2 into the metabolites. The results indicate that
      naphthalene is initially converted to cis- and trans-1,2-dihydroxy-1,2
      dihydronaphthalene by dioxygenase and monooxygenase catalyzed reactions,
      respectively. The ratio of the cis to trans-naphthalene dihydrodiol isomers was
      approximately 25: 1. Thin layer and high pressure liquid chromatographic and mass
      spectrometric techniques indicated that besides the cis- and trans-1,2-dihydroxy
      1,2-dihydronaphthalene, minor amounts of ring cleavage products salicylate and
      catechol were also formed. Thus the formation of both cis and trans-naphthalene
      dihydrodiols by the Mycobacterium sp. is unique. The down-stream reactions to
      ring cleavage products proceed through analogous dioxygenase reactions previously
      reported for the bacterial degradation of naphthalene.

PMID- 1368474
TI  - Dechlorination of pentachlorophenol by membrane bound enzymes of Rhodococcus
      chlorophenolicus PCP-I.
AB  - Dechlorination (para-hydroxylation) of pentachlorophenol (PCP) and tetrachloro
      para-hydroquinone (TeCH) and O-methylation of TeCH were demonstrated in cell
      extracts of Rhodococcus chlorophenolicus PCP-I. PCP para-hydroxylating activity
      was membrane bound, whereas TeCH dechlorinating enzyme was soluble. The PCP para
      hydroxylating enzyme was solubilized by Triton X-100 and the requirement for both
      FAD and NADPH was shown. The dechlorinating activities were inducible in contrast
      to the constitutive TeCH O-methylating activity. The PCP para-hydroxylation was
      inhibited by its product TeCH, by anoxic conditions, and by different inhibitors
      of P450. Participation of this cytochrome in the PCP hydroxylation was confirmed
      by the appearance of a carbon monoxide dependent peak of absorbance at 457 nm in
      the membrane fraction prepared from PCP degrading cells.

PMID- 1368475
TI  - Anaerobic degradation of sorbic acid by sulfate-reducing and fermenting bacteria:
      pentanone-2 and isopentanone-2 as byproducts.
AB  - Strictly anaerobic bacteria were enriched and isolated from freshwater sediment
      sources in the presence and absence of sulfate with sorbic acid as sole source of
      carbon and energy. Strain WoSo1, a Gram-negative vibrioid sulfate-reducing
      bacterium which was assigned to the species Desulfoarculus (formerly
      Desulfovibrio) baarsii oxidized sorbic acid completely to CO2 with concomitant
      stoichiometric reduction of sulfate to sulfide. This strain also oxidized a wide
      variety of fatty acids and other organic compounds. A Gram-negative rod-shaped
      fermenting bacterium, strain AmSo1, fermented sorbic acid stoichiometrically to
      about equal amounts of acetate and butyrate. At concentrations higher than 10 mM,
      sorbic acid fermentation led to the production of pentanone-2 and isopentanone-2
      (3-methyl-2-butanone) as byproducts. Strain AmSo1 fermented also crotonate and 3
      hydroxybutyrate to acetate and butyrate, and hexoses to acetate, ethanol,
      hydrogen, and formate. The guanine-plus-cytosine content of the DNA was 41.8 +/-
      1.0 mol%. Sorbic acid at concentrations higher than 5 mM inhibited growth of this
      strain while strain WoSo1 tolerated sorbic acid up to 10 mM concentration.

PMID- 1368476
TI  - Kinetics of aerobic biodegradation of benzene and toluene in sandy aquifer
      material.
AB  - Monod's equation adequately described aerobic biodegradation rates of benzene and
      toluene by the microbial population of a sandy aquifer when these compounds were
      initially present at concentrations lower than 100 mg/l each. Concentrations
      higher than 100 mg/l were inhibitory, and no benzene or toluene degradation was
      observed when these compounds were initially present at 250 mg/l each. The Monod
      coefficients were calculated as k = 8.3 g-benzene/g-cells/day and Ks = 12.2 mg/l
      for benzene, and k = 9.9 g-toluene/g-cells/day and Ks = 17.4 mg/l for toluene.
      Specific first-order coefficients would be 0.68 l/mg.day for benzene and 0.57
      l.mg.day for toluene.

PMID- 1368477
TI  - Evidence for two distinct phosphonate-degrading enzymes (C-P lyases) in
      Arthrobacter sp. GLP-1.
AB  - Arthrobacter sp. GLP-1 can utilize a wide range of organophosphonates as its sole
      source of phosphorus. The in-situ formation of sarcosine and methane from
      glyphosate and methanephosphonic acid respectively was studied. These two
      processes are differentially induced during phosphorus-deprivation.
      Methanephosphonic acid strongly inhibits glyphosate degradation (I50 10 microM),
      but glyphosate has very little effect on methane generation (I50 150 mM). The
      pattern of inhibition by other organophosphonates and organophosphonate analogues
      is also very different for the two systems. Degradation of glyphosate and
      methanephosphonic acid therefore represent distinct processes.

PMID- 1368478
TI  - Use of antisense RNA to confer bacteriophage resistance in dairy starter
      cultures.
AB  - The strategy and implementation of a unique system for engineering bacteriophage
      resistant starter cultures of Lactococcus lactis employing antisense RNA is
      reviewed. As a necessary prerequisite for developing this system, we have cloned
      and sequenced a number of bacteriophage genes coding for minor and major
      structural proteins. In addition, we have also identified a series of genes whose
      function(s) is not known but their sequences appear to be conserved in a vast
      number of isolates. One of these latter sequences, designated gp51C, codes for a
      51-kDa protein which is extremely charged and shares some homology with yeast
      translation initiation factor. Resistance to a broad class of isometric
      bacteriophages has been achieved by expression of an antisense RNA targeted
      against, for example, gp51C. In the best case, expression of the antisense gp51C
      RNA results is a greater than 99% reduction in the total number of plaque forming
      units. Additional antisense RNA constructs directed against other bacteriophage
      genes, including the major capsid protein, also appear effective at inhibiting
      infection from 40-55% suggesting that this approach may prove useful for
      engineering a set of truly isogenic strains to be used in a starter culture
      rotation plan.

PMID- 1368479
TI  - Maintenance and killing efficiency of conditional lethal constructs in
      Pseudomonas putida.
AB  - Conditional lethal (suicidal) genetic constructs were designed and employed in
      strains of Pseudomonads as models for containment of genetically-engineered
      microbes that may be deliberately released into the environment. A strain of
      Pseudomonas putida was formed with a suicide vector designated pBAP24h that was
      constructed by cloning the host killing gene (hok) into the RSF1010 plasmid
      pVDtac24 and placing it under the control of the tac promoter. After hok
      induction in P. putida only 40% of surviving cells continued to bear the hok
      sequences within 4 h of induction; in contrast, 100% of the cells in uninduced
      controls bore hok. A few survivors that demonstrated resistance to hok-induced
      killing developed in P. putida, which may have been due to a mutation or
      physiological adaptation that rendered the membrane 'resistant' to hok.
      Conditional lethal strains of P. putida also were formed by inserting gef (a
      chromosomal homolog of hok) under the control of the tac promoter into the
      chromosome using a transposon. Constructs with chromosomal gef, as well as an RK2
      derived plasmid construct containing gef, were only marginally more stable than
      the hok constructs; they were effective in killing P. putida when induced and
      within 2 h post-induction killing from either gef construct resulted in a 10(3)
      10(5)-fold reduction in viable cell count compared to uninduced controls.

PMID- 1368480
TI  - Interactions in the fourth dimension.

PMID- 1368481
TI  - Validating the preparation of clinical monoclonal antibodies.

PMID- 1368482
TI  - Electrophoresis in thin air.

PMID- 1368483
TI  - Agenda 21: biotechnology at the United Nations Conference on Environment and
      Development.

PMID- 1368484
TI  - Ribosome-inactivating proteins from plants: present status and future prospects.
AB  - Plant ribosome-inactivating proteins (RIPs) are N-glycosidases which cleave the N
      glycosidic bond of adenine in a specific ribosomal RNA sequence. Most commonly
      RIPs are single-chain proteins (type 1 RIPs), but some (type 2 RIPs) possess a
      galactose-specific lectin domain that binds to cell surfaces. The latter RIPs are
      potent toxins, the best known of which is ricin. RIPs have antiviral and
      abortifacient activities, and, in a widespread application, can also be linked to
      antibodies or ligands to form immunotoxins or conjugates specifically toxic to a
      given type of cell.

PMID- 1368485
TI  - Simultaneous amplification and detection of specific DNA sequences.
AB  - We have enhanced the polymerase chain reaction (PCR) such that specific DNA
      sequences can be detected without opening the reaction tube. This enhancement
      requires the addition of ethidium bromide (EtBr) to a PCR. Since the fluorescence
      of EtBr increases in the presence of double-stranded (ds) DNA an increase in
      fluorescence in such a PCR indicates a positive amplification, which can be
      easily monitored externally. In fact, amplification can be continuously monitored
      in order to follow its progress. The ability to simultaneously amplify specific
      DNA sequences and detect the product of the amplification both simplifies and
      improves PCR and may facilitate its automation and more widespread use in the
      clinic or in other situations requiring high sample throughput.

PMID- 1368486
TI  - Increased resistance to potato virus X and preservation of cultivar properties in
      transgenic potato under field conditions.
AB  - During the last three years we performed field trials to assess levels of
      resistance against potato virus X (PVX) and changes in intrinsic properties of
      the potato cultivars Bintje and Escort upon the introduction of the PVX coat
      protein (CP) gene. Analysis of leaf and tuber samples collected in the field at
      two week intervals revealed a stable expression of the PVX CP gene throughout the
      growing season. This resulted in a large decrease in PVX incidence among clonal
      progeny obtained from previously infected Bintje and Escort clones. Based on
      evaluation of 50 defined morphological characteristics, tuber yield and grading,
      81.8% of the Escort and 17.9% of the Bintje derived transgenic clones proved to
      be true to type. Overall lightsprout morphology was a useful criterion for the
      early detection of deviant transgenic clones. Using the polymerase chain reaction
      (PCR) with convergent primers spanning transgenic sequences, true to type clones
      could be distinguished unambiguously from the corresponding untransformed
      cultivars. Clear distinctions between independent transgenic clones could be made
      by inverted PCR (IPCR) diagnosis revealing integration-specific border fragments.
      These results demonstrate the commercial feasibility of improving potato
      cultivars by selectively adding new traits while preserving intrinsic properties,
      and the possibility of unambiguously identifying independent transgenic
      cultivars.

PMID- 1368487
TI  - Antigen responsive antibody-receptor kinase chimera.
AB  - We have constructed chimeric receptors, combining murine IgM and the cytoplasmic
      portion of human epidermal growth factor receptor (EGFR), with the aim of
      developing a novel immunosensor with antigen-dependent phosphorylation activity.
      When intact IgM was used, the chimeric receptor showed both antigen binding and
      protein tyrosine kinase activity, but the kinase activity was constitutive and
      independent of antigen binding. However, with IgM lacking the CH2 domain, the
      autophosphorylation activity increased with increasing concentrations of anti-IgM
      or hapten-BSA conjugate. Monovalent hapten could not induce phosphorylation but
      inhibited stimulation by hapten-conjugated BSA.

PMID- 1368488
TI  - Cysteine to serine substitutions in basic fibroblast growth factor: effect on
      inclusion body formation and proteolytic susceptibility during in vitro
      refolding.
AB  - We have investigated the effect of cysteine to serine substitutions in human
      basic fibroblast growth factor (bFGF) on the formation of inclusion bodies in
      Escherichia coli. Using a temperature-sensitive expression, system, about 30% of
      human bFGF, which contains four cysteines at positions 26, 70, 88, and 93, is
      deposited into inclusion bodies. A single mutation at position 88 and a double
      mutation at positions 70 and 88 do not greatly alter the partition of bFGF into
      soluble and insoluble cell fractions. However, a single substitution of cysteine
      70 by serine decreases the fraction of soluble bFGF significantly. When cysteines
      26 and 93 (conserved among related growth factors) are replaced by serines, no
      soluble bFGF is formed in E. coli. Cysteine to serine substitutions also affect
      proteolytic susceptibility of bFGF during in vitro refolding from crude inclusion
      bodies. About 60% of human bFGF is lost to proteolytic degradation during in
      vitro refolding. Replacement of cysteines by serines increases the total recovery
      of bFGF, although more aggregates are formed during refolding. Ser-88-bFGF was
      expressed at the highest level, gave the highest soluble fraction in vivo, and
      exhibited the greatest fractional recovery and was recovered with the largest
      insoluble fraction after in vitro refolding. Thermal stability experiments at 42
      degrees C and 70 degrees C revealed that cysteine to serine substitutions did not
      cause aggregation of the folded protein in vitro.

PMID- 1368490
TI  - Serum supply.

PMID- 1368489
TI  - Monoclonal antibodies can protect L-asparaginase against inactivation by trypsin.
AB  - We show that a non-inhibitory monoclonal antibody (MAB) can be selected that
      provides substantial and sustained protection against proteolytic inactivation of
      L-asparaginase by trypsin. Of six non-inhibitory, high affinity, monoclonal
      antibodies to L-asparaginase, one afforded approximately 70% protection.
      Inactivation of L-asparaginase is associated with a single cleavage adjacent to
      lysine-29 that results in loss of an N-terminal fragment with a calculated MW of
      2,647. The protective MAB prevented this trypsin cleavage. The products of gene
      fusions of "humanized" fragments of such antibodies and L-asparaginase could have
      increased clinical utility.

PMID- 1368491
TI  - Serum supply.

PMID- 1368492
TI  - Controversial comments.

PMID- 1368494
TI  - Controversial comments.

PMID- 1368493
TI  - Controversial comments.

PMID- 1368495
TI  - Gene fragments.

PMID- 1368496
TI  - Comparison of the catalytic and inhibitory properties of Pachysolen tannophilus
      xylose reductase to rat lens aldose reductase.
AB  - The catalytic and inhibitory profiles of xylose reductase isolated from the yeast
      Pachysolen tannophilus (PTXR) are compared to those of aldose reductase (AR)
      obtained from rat lens. While both PTXR and rat lens AR are NADPH-specific
      enzymes and have an affinity for a variety of substrates such as D-xylose, D,L
      glyceraldehyde, and 4-nitrobenzaldehyde, the enzymes differ in their substrate
      affinity profiles. Also, PTXR is not inhibited by standard inhibitors of AR thus
      supporting a hypothesis that this enzyme may not possess the inhibitor binding
      site found in rat lens AR.

PMID- 1368497
TI  - Start-up of a thermophilic upflow anaerobic sludge bed (UASB) reactor with
      mesophilic granular sludge.

PMID- 1368498
TI  - Quantification of denitrification by strain T1 during anaerobic degradation of
      toluene.
AB  - Strain T1 is a denitrifying bacterium that is capable of toluene degradation
      under anaerobic conditions. During anaerobic growth on toluene, the specific
      growth rate of strain T1 was 0.14 h-1. Nitrite accumulated in the medium
      stoichiometrically with the depletion of nitrate. When nitrate was nearly
      depleted from the medium nitrite reduction and dinitrogen formation began. A non
      kinetic model was formulated that was based on a hypothesis of non-simultaneous
      nitrate and nitrite reduction, independent of the concentrations of nitrate and
      nitrite. The model was verified experimentally over a wide range of conditions
      that included nitrate and nitrite limitation, toluene limitation, and various
      ratios of nitrate to nitrite. The model and its experimental verification
      demonstrated that strain T1 reduces nitrate and nitrite non-simultaneously, even
      if nitrite is initially present in the medium in addition to nitrate.

PMID- 1368499
TI  - Stereoselective epoxidation of phenyl allyl ether by alkene-utilizing bacteria.
AB  - Eighteen newly isolated ethene- and propene-utilizing bacteria were screened for
      the ability to produce phenyl glycidyl ether, a common precursor for the
      synthesis of beta blockers, from phenyl allyl ether. These organisms included
      Aerococcus, Alcaligenes, Micrococcus and Staphylococcus spp. and a variety of
      Gram-negative, Gram-positive and Gram-variable mesophilic rods/coccobacilli not
      yet identified. The majority of ethene- and propene-grown cultures (14 strains)
      accumulated phenyl glycidyl ether (0.4-1.7 mM) as the sole oxidation product. The
      bioconversions with the three most promising ethene-utilizers (M26, M90C, M93A)
      were scaled-up to yield essentially optically pure (enantiomeric excess = 93%) S
      (+)-phenyl glycidyl ether. This is currently under investigation for commercial
      production of optically pure beta blockers.

PMID- 1368500
TI  - Batch and continuous ribonuclease production by immobilized Aspergillus clavatus
      cells in a bubble-column bioreactor.
AB  - Ribonuclease production using immobilized cells (IC) of Aspergillus clavatus has
      been studied under batch, repeated-batch and continuous fermentation conditions
      in a bubble-column bioreactor and compared with production by free cells.
      Immobilization was achieved by the method of cryostructurization in polyvinyl
      alcohol beads. The effect of various aeration rates in a column bioreactor has
      been investigated. Enzyme production by IC [42,000 units (U).1(-1)] during batch
      fermentations was comparable to that of a free-cell system. The specific
      productivity of IC was 8.5 times higher than that of free cells. In repeated
      batch fermentation at various aeration rates, successful reuse of IC was
      obtained, with comparable levels of enzyme production. Continuous ribonuclease
      production was achieved for 44 days at 1 vvm aeration and a dilution rate of 0.01
      h-1 with high volumetric productivity (450 U.1-1.h-1) and yield.

PMID- 1368501
TI  - The effect of Pluronic F-68 on hybridoma cells in continuous culture.
AB  - The comparative effects of Pluronic on cell growth of hybridomas were studied.
      The addition of 0.05% Pluronic decreased the steady-state cell number in
      continuous culture by about 12% compared to a non-supplemented culture. In short
      term experiments, results demonstrated a gradual decrease in cell number with
      increasing concentration of Pluronic. Such growth inhibition was found to be a
      result of lowering the rate of DNA synthesis.

PMID- 1368502
TI  - Optimization of protein-production by the baculovirus expression vector system in
      shake flasks.
AB  - Shake flasks were successfully employed for the cultivation of Spodoptera
      frugiperda (Sf-9) insect cells and for the production of beta-galactosidase, a
      recombinant model protein, utilizing the baculovirus expression vector system.
      The culture doubling time and maximal cell density were 20 h and 5 x 10(6)
      cells/ml respectively. The optimal liquid volumes for flasks rotating at 100 rpm
      were 25-40% of the flask total volume. Enzyme production (about 600 mg/l) was
      best at a multiplicity of infection of between 1 and 20 and at a cell density at
      time of infection of 0.7 x 10(6) cells/ml. At a rotation speed of 100 rpm,
      Pluronic F-68 had no effect on growth and enzyme production.

PMID- 1368503
TI  - Antisense RNA directed against the major capsid protein of Lactococcus lactis
      subsp. cremoris bacteriophage 4-1 confers partial resistance to the host.
AB  - Antisense RNA targeted against the major capsid protein (MCP) of Lactococcus
      lactis subsp. cremoris bacteriophage F4-1 reduced bacteriophage replication by up
      to 50%. The region containing the mcp gene was oriented to transcribe the
      antisense strand using a L. lactis subsp. cremoris Wg2 promoter. The size of the
      mcp insert transcribed affected the level of bacteriophage inhibition and the
      greatest level of inhibition was achieved using a 301-bp fragment from the 5' end
      of the mcp. Antisense mcp RNA constructs were stable and did not alter the
      endogenous plasmid profile in the host, L. lactis subsp. cremoris F4-1. There
      were, however, some adverse effects on the host during the stationary phase as
      exhibited by a decline in cell density.

PMID- 1368504
TI  - Affairs of the heart.

PMID- 1368505
TI  - Cloning and heterologous expression of the penicillin biosynthetic gene cluster
      from penicillum chrysogenum.
AB  - A cosmid clone containing the putative penicillin biosynthetic gene cluster from
      Penicillium chrysogenum was used to transform the related filamentous fungi
      Neurospora crassa and Aspergillus niger, which do not produce beta-lactam
      antibiotics. Both of the transformed hosts contained intact P. chrysogenum DNA
      derived from the cosmid clone and produced authentic penicillin V. Assays of
      penicillin biosynthetic enzyme activity additionally demonstrated that they
      possessed delta-(L-alpha-amino-adipyl)-L-cysteinyl-D-valine synthetase (ACVS),
      isopenicillin N synthetase (IPNS) and acyl coenzyme A:6-aminopenicillanic acid
      acyltransferase (ACT) activity. The data suggests that genes encoding all the
      enzymes necessary for the biosynthesis of penicillin from amino acid precursors
      are closely linked in P. chrysogenum and constitute a gene cluster.

PMID- 1368507
TI  - Beta-eliminative cleavage of the acidic polysaccharide of Fusarium sp. M7-1 by an
      enzyme preparation of Cellulomonas sp.
AB  - By digestion with an enzyme preparation derived from a culture filtrate of
      Cellulomonas sp., an unsaturated disaccharide was produced accompanied by the
      release of mannose and beta 1----2 mannobiose from the acidic oligomer mixture
      that was obtained from the acidic polysaccharide of Fusarium sp. M7-1 by
      acetolysis. The unsaturated disaccharide produced was isolated and identified as
      4-deoxy-L-threo-hex-4-enopyranouronosyl alpha(1----2)-D-galactose. The same
      unsaturated sugar linked to the polysaccharide was also produced accompanied by
      the release of mannose and beta 1----2 mannobiose from the acidic polysaccharide
      by the enzyme digestion.

PMID- 1368506
TI  - Selective determination of L-lysine with L-lysine epsilon-dehydrogenase.
AB  - Simple and sensitive spectrophotometric methods were developed for the selective
      determination of L-lysine. The assay methods were based on the spectrophotometric
      determination of NADH formed in the reaction catalyzed by L-lysine epsilon
      dehydrogenase (Procedure A) or the formazan produced on coupling of the
      dehydrogenase reaction with the reduction of a tetrazolium salt (Procedure B).
      Procedure B was applicable to the direct determination of L-lysine in rabbit
      serum.

PMID- 1368508
TI  - Construction of shuttle vector plasmid between Clostridium acetobutylicum and
      Escherichia coli.
AB  - A high copy number plasmid pCS86 (3.0 kb) was isolated from Clostridium
      acetobutylicum strain No. 86. For developing the vector plasmid for gene cloning
      of saccharolytic clostridia, two hybrid plasmids were constructed by joining
      pCS86 to the E. coli promoter probe vector pKK232-8 carrying the promoterless
      gene of chloramphenicol acetyltransferase (CAT). One of the hybrid plasmids
      designated as pTY10 replicated and expressed the CAT gene in E. coli, and
      transformed a plasmid-free strain, C. acetobutylicum strain No. 220, as a shuttle
      vector. This is the first shuttle vector constructed from C. acetobutylicum and
      E. coli plasmids. Reciprocal transformation was possible between E. coli and C.
      acetobutylicum, though deletion occurred in the sequence originated from pKK232
      8. A deleted plasmid pTY101 only replicated in Clostridium, though it showed a
      high copy number.

PMID- 1368509
TI  - Electroporation-transformation system for coryneform bacteria by auxotrophic
      complementation.
AB  - We evaluated electroporation as an alternative system for genetic exchange for
      one of the coryneform bacteria, Brevibacterium flavum MJ233. The maximum number
      of transformants, 6 x 10(4) cells, was obtained when cells were cultured with
      Penicillin G (1 U/ml) and harvested at the middle-log phase. Electroporation was
      done using 12.5 kV/cm of pulse field strength, 1 x 10(10) cells, and 1 microgram
      of plasmid DNA. Other coryneform bacteria, Brevibacterium lactofermentum ATCC
      13869, Corynebacterium glutamicum ATCC 31830, and B. stationis IFO 12144 were
      also transformed by electroporation. Electroporation has the advantage that
      intact cells can be used as host cells without the need for protoplast formation
      and regeneration. Moreover, minimal medium can be used, so auxotrophic
      complementation of the transformants is possible.

PMID- 1368510
TI  - Structure of rice-straw arabinoglucuronoxylan and specificity of Streptomyces
      xylanase toward the xylan.
AB  - Rice-straw treated with 5% ammonia water was hydrolyzed with the beta-xylanase of
      Streptomyces sp. E-86, and four kinds of hetero-oligosaccharides, two arabinoxylo
      and two glucuronoxylo-oligosaccharides, were isolated from the hydrolysate by
      charcoal column, gel filtration, ion-exchange, and aminopropyl silica column
      chromatographies. The structures of the oligosaccharides were identified as 3(2)
      alpha-L-arabinofuranosyl-xylobiose, 3(2)-alpha-L-arabinofuranosylxylotriose, 2(3)
      4-O-methyl-alpha-D-glucuronosylxylotriose, and 2(3)-alpha-D
      glucuronosylxylotriose by the analysis of component sugar, partial acid
      hydrolysis, methylation analysis etc. Based on the structures of above
      oligosaccharides, the structure of rice-straw arabinoglucuronoxylan and the
      specificity of the xylanase toward the xylan are discussed.

PMID- 1368511
TI  - Purification and characterization of citrate synthase from Streptomyces
      hygroscopicus SF-1293 and comparison of its properties with those of 2
      phosphinomethylmalic acid synthase.
AB  - To study the relationship between citrate synthase and 2-phosphinomethylmalic
      acid (PMM) synthase, which catalyzes a very similar reaction comparable to
      citrate formation in the biosynthesis of a herbicide, bialaphos, citrate synthase
      was purified from the mycelium of Streptomyces hygroscopicus SF-1293, a bialaphos
      producing organism. The overall purification was 440-fold with a yield of 4.4%
      from cell-free extract. Based on comparison with PMM synthase, it has been
      concluded that citrate synthase of S. hygroscopicus is quite different from PMM
      synthase in several aspects such as enzymatic properties, amino acid composition.
      N-terminal amino acid sequence, and stereo-chemical reaction mechanism.

PMID- 1368512
TI  - Structural characterization of the immunoactive and antiviral water-solubilized
      lignin in an extract of the culture medium of Lentinus edodes mycelia (LEM).
AB  - The active principle of EP3, a fraction from an extract of the culture medium of
      Lentinus edodes mycelia (LEM), which activates murine macrophages, causes
      proliferation of bone marrow cells, and inhibit the replication of Human
      Immunodeficiency Virus in vitro, was characterized as a water-solubilized lignin.
      The detailed structural feature of this water-solubilized lignin was investigated
      and shown to be a highly condensed and polycarboxylated lignin which is denatured
      and solubilized by Lentinus edodes from bagasse. The water-solubilized lignin
      itself was confirmed to have both immunological activities and the antiviral
      activity.

PMID- 1368514
TI  - Immunological properties of lectins from green shells of winged bean, and N
      terminal amino acid sequence of basic seed lectin-like green shell lectin.

PMID- 1368513
TI  - Identification of soybean protein components that modulate the action of insulin
      in vitro.
AB  - We have reported that a 37-kDa protein from a soybean isolate shows an affinity
      for bile acids and modulates insulin action on fat decomposition in vitro [Makino
      et al., Agric. Biol. Chem., 52, 803 (1988)]. In this study, the major components
      of the protein were identified as the acidic A1a and A2 subunits of glycinin, via
      amino-terminal sequence analyses of purified proteins and examination of their
      effects on fat decomposition in rat adipose cells. The most hydrophobic region of
      the subunits was found to be responsible for the bile acid-binding ability, and
      the binding region probably does not contribute to the insulin-modulating
      activity. These bile acid-binding and insulin-modulating properties were also
      noted in a 40-kDa protein from pea seeds, probably acidic subunits of legumin,
      suggesting that these characteristics may be common to legume proteins.

PMID- 1368516
TI  - Single site proteolysis in silkworm antitrypsin causes structural changes in
      behavior against denaturing reagents.
AB  - Silkworm antitrypsin (sw-AT), which was thought to belong to serpin family,
      changed its behavior against denaturation after chymotryptic cleavage of a single
      peptide bond (Tyr-Val) two amino acids away from the reactive site for trypsin
      (Lys-Val). This chymotrypsin-modified sw-AT became resistant to denaturation by
      heat, sodium dodecyl sulfate, or guanidine hydrochloride, and this characteristic
      was evident in its circular dichroism spectrum. The modified sw-AT was also
      indigestible by S. aureus V8 protease. These facts should indicate a structural
      change from a stressed, unstable state to a stable one accompanying the cleavage
      of the single peptide bond in sw-AT. The stabilizing factor was in part
      attributed to the interaction of a COOH-terminal fragment (5 kDa) and an NH2
      terminal one (36 kDa) in modified sw-AT.

PMID- 1368515
TI  - Limited proteolysis of silkworm antitrypsin by several proteinases.
AB  - Silkworm antitrypsin (sw-AT) isolated from larval hemolymph was limitedly
      digested by Achromobacter lysylendopeptidase, alpha-chymotrypsin, subtilisin
      BPN', subtilisin Carlsberg, papain, or Pseudomonas elastase. Each proteinase
      could cleave specific site(s) around the reactive site identified for the
      reaction of sw-AT and bovine trypsin. Among these proteinases, only subtilisin
      BPN' was inhibited by sw-AT, although weakly. By the cleavable amino acid
      sequence in sw-AT, it was suggested that whether or not these proteinases were
      inhibited by sw-AT did not solely depend on their substrate specificities. The
      susceptibility to the attack of proteinase should indicate that this region is
      exposed on the molecular surface. The amino acid sequence in the COOH-terminal
      region slightly away from the reactive site in sw-AT had homology with that in
      the corresponding region of the serine proteinase inhibitor (serpin) group.

PMID- 1368517
TI  - Structural analyses of sugar chains from ricin A-chain variant.
AB  - Two glycopeptides were isolated from a tryptic digest of ricin A-chain variant by
      gel filtration and reversed-phase HPLC. Their amino acid compositions and
      sequences showed that Asn-10 and Asn-236 are glycosylated. The sugar chains were
      liberated from these glycopeptides by hydrazynolysis, N-acetylated, and
      pyridylaminated. Component analysis and comparison of elution positions of the
      purified pyridylamino (PA-) sugar chains with those of authentic PA-sugar chains
      from the major ricin A-chain by reversed-phase HPLC and size fractionation HPLC
      suggested that both sugar chains linked to Asn-10 and Asn-236 of the ricin A
      chain variant are M3FX, identical to that linked to Asn-10 of the major ricin A
      chain.

PMID- 1368518
TI  - Subunit structure of karatasin, the proteinase isolated from Bromelia plumieri
      (karatas).
AB  - Close to 15% of the karatasin proteinase activity in the fruit juice of Bromelia
      plumieri (karatas) is present outside dialysis Visking tubing in 7 days in 0.2 M
      acetate buffer (pH) 3.5 or 6.5) containing phenyl mercuric acetate. The small
      proteinase(s), distinct from the 85% activity in juice due to nondialysable
      karatasin with a reported Mr of 24,868, separates across Spectrapore (13 kDa)
      membranes but not across Spectrapore with 3.5 kDa average pore diameter. The
      dialyzed proteinase is named karatasin-D (K-D). Purified non-Dialysable karatasin
      can be dissociated to what seems to be K-D by incubation in a buffer solution,
      containing SDS and 2-mercaptoethanol with phenyl mercuric acetate, in dialysis
      experiments for 8 days at room temperature using Spectrapore 13 kDa tubing. Thus,
      native karatasin in B. plumieri fruit juice seem to be the result of association
      of 2 small molecular mass K-D subunits, linked together by disulfide bonds and
      electrostatic forces, in equilibrium with small amounts of free K-D molecules.
      The amino acid composition and partial sequence of karatasin up to the 14th
      position from the amino terminus have discrete analogies with papain and with
      stem bromelain.

PMID- 1368519
TI  - Comparison of CD composition produced by chimeric CGTases.
AB  - Using 12 chimeric cyclomaltodextrin glucanotransferases (CGTases) constructed
      from two genes, the CGTase gene from the alkalophilic Bacillus sp. strain No. 38
      2 (CGTase 38-2 gene) and the CGTase gene from the alkalophilic Bacillus sp.
      strain No. 17-1 (CGTase 17-1 gene), we compared the effect of those chimeric
      enzymes on cyclodextrin (CD) production, especially on the composition of the CDs
      produced. It was found that the N-terminal and the C-terminal segments were
      important for CD production. Chimeric enzymes that contained the N-terminal and
      the C-terminal segments derived from CGTase 38-2 produced large amounts of CD,
      and especially a higher proportion of alpha-CD than those of other chimeric
      enzymes.

PMID- 1368520
TI  - Intraspecific protoplast fusion of Lactobacillus plantarum.

PMID- 1368521
TI  - Production of active phosphoenolpyruvate carboxylase of Zea mays in Escherichia
      coli encoded by a full-length cDNA.

PMID- 1368522
TI  - Primary structure of rat monoamine oxidase A deduced from cDNA and its expression
      in rat tissues.
AB  - The cDNA for rat monoamine oxidase A (MAO-A) mRNA was isolated from a liver cDNA
      library in lambda gt11 as the cDNA species cross-hybridizing with rat monoamine
      oxidase B (MAO-B) cDNA. The primary structure of the protein, deduced from the
      nucleotide sequence, consisted of 526 amino acid residues and its molecular mass
      was calculated to be 59.6 kD. The amino acid sequence shows about 70% identity
      with that of rat MAO-B. Northern blot analysis showed that MAO-B mRNA was
      expressed in various rat tissues and the highest expression was observed in
      heart. The MAO-B mRNA was quite different from MAO-A mRNA in the tissue-specific
      expression and liver had the highest level of the mRNA.

PMID- 1368523
TI  - Partial purification and substrate specificity of acylamino acid-releasing enzyme
      from Rhodotorula glutinis.

PMID- 1368524
TI  - A new restriction endonuclease from Bacteroides distasonis (BdiI).

PMID- 1368525
TI  - Practical debittering using model peptides and related compounds.
AB  - In order to develop a practical debittering method for amino acids and peptides,
      several debittering methods were studied. The authors found that hooking acidic
      amino acids to and acetylation of bitter amino acids is very effective to remove
      the bitterness from their concentrated solution. For debittering by mixing with
      additives, skin milk and other peptide compounds were effective. Acidic amino
      acids were also effective to reduce the bitterness. Gelatinized starch was found
      to be useful for debittering because it takes bitter substances into its net
      structure.

PMID- 1368526
TI  - Molecular and kinetic properties of Aspergillus ficuum inulinases.
AB  - The beta-fructosidases from the thermotolerant fungus, A. ficuum, were
      characterized. All were active as to inulin and sucrose hydrolysis with different
      specificity constants (kcat/Km). The enzymes were classified according to the
      ratio (alpha) of the specificity constants for inulin (I) and sucrose (S). The
      invertase showed an alpha value of lower than one, while the inulinases had alpha
      values of higher than one. The alpha ratio is proposed for the classification of
      beta-fructosidases into the inulinase (EC 3.2.1.7) and invertase (EC 3.2.1.26)
      groups. The amino acid composition, pH and temperature profiles,
      ultracentrifugation analysis results and effects of metal ions and effectors were
      studied. The data confirmed the preceding classification based on the I/S ratio,
      on the mode of action of inulinases (exo or endo) during inulin hydrolysis and on
      the molecular properties of the proteins.

PMID- 1368527
TI  - The effects of metal ions on the DNA damage induced by hydrogen peroxide.
AB  - The effects of metal ions on DNA damage induced by hydrogen peroxide were
      investigated using two methods, agarose-gel electrophoretic analysis of
      supercoiled DNA and sequencing-gel analysis of single end-labeled DNA fragments
      of defined sequences. Hydrogen peroxide induced DNA damage when iron or copper
      ion was present. At least two classes of DNA damage were induced, one being
      direct DNA-strand cleavage, and the other being base modification labile to hot
      piperidine. The investigation of the damaged sites and the inhibitory effects of
      radical scavengers revealed that hydroxyl radical was the species which attacked
      DNA in the reaction of H2O2/Fe(II). On the other hand, two types of DNA damage
      were induced by H2O2/Cu(II). Type I damage was predominant and inhibited by
      potassium iodide, but type II was not. The sites of the base-modification induced
      by type I damage were similar to those by lipid peroxidation products and by
      ascorbate in the presence of Cu(II), suggesting the involvement of radical
      species other than free hydroxyl radical in the damaging reactions.

PMID- 1368528
TI  - Purification and characterization of a novel fungal endo-beta-N
      acetylglucosaminidase acting on complex oligosaccharides of glycoproteins.
AB  - A novel endo-beta-N-acetylglucosaminidase acting on complex type sugar chains of
      glycoproteins was found in the culture broth of a fungus isolated from soil and
      identified as Mucor hiemalis f. hiemalis on the basis of various characteristics.
      The endo-beta-N-acetylglucosaminidase, named Endo-M, was purified to almost
      homogeneity by polyacrylamide gel electrophoresis involving ammonium sulfate
      fractionation, and column chromatographies on DEAE-Sepharose CL-6B, Sephadex G
      200, hydroxylapatite, TSK-gel HW-65F and Con A-Sepharose 4B. The molecular weight
      of the enzyme was estimated to be about 95,000 by gel chromatography. The optimum
      pH was found to be 6.0-6.5 and the enzyme was stable in the pH range of 7 to 8.
      The enzyme showed high activity on dansyl ovalbumin glycopeptide, and also could
      act on dansyl transferrin glycopeptide, and dansyl asialotransferrin glycopeptide
      containing biantennary complex type sugar chains. The Km value for dansyl
      asialotransferrin glycopeptide as the substrate was 2.0 x 10(-3) M. The enzyme
      released complex type sugar chains from intact asialotransferrin without the
      addition of any detergent and the liberated sugar chains were identified by
      chromatography on a Bio-Gel P-4 column, calibrated with markers of known
      structure, and 1H-NMR analysis.

PMID- 1368529
TI  - Enzymatic synthesis of p-nitrophenyl alpha-maltoheptaoside by transglycosylation
      of maltohexaose-forming amylase.
AB  - An extracellular maltohexaose-forming amylase [EC 3.2.1.98] from Klebsiella
      pneumoniae mutant is a normal hydrolytic enzyme that hydrolyzes short-chain
      amylose (DP = 23) to give about 40% maltohexaose. Transglycosylation from
      maltoheptaose to the 4-position of p-nitrophenyl alpha-glucoside was efficiently
      induced through the use of maltohexaose-forming amylase in an aqueous methanol
      solution. The enzyme specifically produced p-nitrophenyl alpha-maltoheptaoside
      (13% of the p-nitrophenyl alpha-glucoside) from maltoheptaose as a donor and p
      nitrophenyl alpha-glucoside as an acceptor. The yield of p-nitrophenyl alpha
      maltoheptaoside depended on the concentration of methanol solvent, the pH, and
      temperature. Furthermore, the use of the aqueous methanol system in the reaction
      not only improved the solubility of p-nitrophenyl alpha-glucoside but also
      greatly increased the formation of p-nitrophenyl alpha-maltoheptaoside, which is
      a useful substrate for assay of human amylase in serum and urine.

PMID- 1368530
TI  - Immunochemical analysis of the glucomannan from Candida utilis.
AB  - A glucomannan isolated from a Candida utilis mutant having a new chemotype was
      further studied by inhibition of the homologous precipitin reaction with
      oligosaccharides obtained from the glucomannan by partial acid hydrolysis and
      controlled acetolysis. Oligosaccharides having at least two consecutive alpha-(1-
      --2)-linked mannose residues at the non-reducing end and gluco-manno
      pentasaccharide were effective inhibitors. Thus, it appears that the glucomannan
      had two groups of antigenic determinants, one corresponding to the side chains of
      two, three, and four mannose units connected by alpha-(1----2)-linkage, and the
      other corresponding to a side chain composed of an O-alpha-D-glucopyranosyl-(1---
      6)-O-alpha-D-mannopyranosyl- (1----2)-O-alpha-D-mannopyranosyl-(1----2)-D-mannose
      unit. These results support a probable structure of repeating units for the
      glucomannan presented previously. The relative susceptibility of intersaccharidic
      linkages to acid hydrolysis in the mannan is discussed.

PMID- 1368531
TI  - Deletion of D-helix in bovine pancreatic phospholipase A2.
AB  - D-Helix-deleted bovine pancreatic phospholipase A2 was designed using molecular
      mechanic calculations, and synthesized. Effects of the deletion on the enzymatic
      activity and on the structure were investigated. The enzymatic activity of the
      mutant protein was about 40% of that of the native one for a micellar substrate
      of 1,2-dioctanoyl-phosphatidylcholine. Although the Michaelis constant of the
      mutant enzyme was not changed, the catalytic constant was decreased. The
      dissociation constant of calcium ion was also changed. 1H NMR study revealed a
      slight conformation change around the active site of the mutant enzyme in
      addition to changes around the mutated region. The effect on the activity of the
      mutation seems to be due to the conformational changes around the active site.

PMID- 1368533
TI  - Stereoselective synthesis of marine antibiotic (-)-malyngolide and its
      stereoisomers.
AB  - A convenient synthetic method for the marine antibiotic (-)-malyngolide and its
      stereoisomers was accomplished from a chiral alpha-alkoxyketone (4), which was
      readily available as a chiron. Chiral quaternary carbon synthons (5a) and (5b) as
      the key intermediates were constructed by the chelation controlled addition of
      Grignard reagent to 4. The diastereomeric mixture of 5a and 5b was readily
      transformed into a separable mixture of lactones (7a) and (7b), each of which
      could be easily separated by silica-gel column chromatography. (-)-Malyngolide
      and its three stereoisomers were obtained in optically pure form without the need
      for optical resolution.

PMID- 1368532
TI  - Expression of the beta-cyclodextrin glucanotransferase gene of an alkalophilic
      Bacillus sp. #1011 in Escherichia coli cells and characterization of the
      synthesized enzyme.
AB  - To express efficiently the gene for extracellular beta-cyclodextrin
      glucanotransferase (beta-CGTase) of an alkalophilic Bacillus sp. #1011 using the
      E. coli promoters (tac, trp and PL promoters), three DNA fragments starting from
      the nucleotide positions +1, -18, and -48 of the translation initiation site of
      the gene were prepared and they were fused with the promoters. The maximum
      production of the enzyme, which was located mainly (90%) in the periplasm of the
      E. coli strain, was observed in the combination of the trp promoter and the beta
      CGTase gene starting from the -48 nucleotide position in the presence of the
      inducer, IAA. The production of the enzyme was increased to 5.5 times that by the
      E. coli harboring the original plasmid and to approximately 3 times higher than
      the extracellular production of the enzyme by the parental Bacillus sp. #1011.
      The properties including the stability and optimum in the high pH range (pH 9) of
      the extracellular beta-CGTase from the alkalophilic Bacillus was conserved in the
      periplasmic enzymes of the E. coli cells.

PMID- 1368534
TI  - Construction of chimeric insecticidal proteins between the 130-kDa and 135-kDa
      proteins of Bacillus thuringiensis subsp. aizawai for analysis of structure
      function relationship.
AB  - Eight chimeric insecticidal protein (IP) genes were constructed between the 130
      kDa and 135-kDa IP genes of Bacillus thuringiensis subsp. aizawai, and expressed
      in Escherichia coli JM103 cells. The characterization of the produced chimeric
      IPs indicated that the variable region (VR1) in the amino-terminal half of the
      IPs is responsible for the insecticidal activity against larvae of Spodoptera
      litura and Plutella xylostella. The carboxy-terminal half of VR1 was important
      for the formation of the 60-kDa active fragment in the gut juice of S. litura
      larvae. Also, combination of the other two variable regions (VR2 and VR3), which
      were in the central and carboxy-terminal portions of the IPs, appeared to be
      related to the solubility of the IPs in the gut juice.

PMID- 1368535
TI  - Purification and characterization of two forms of maltotetraose-forming amylase
      from Pseudomonas stutzeri.
AB  - Pseudomonas stutzeri MO-19 produced two active forms of extracellular
      maltotetraose-forming amylase. Both forms, G4-1 and G4-2, were purified to
      electrophoretic homogeneity. The molecular masses of G4(-1) and G4(-2) were 57 kd
      and 46 kd by SDS-polyacrylamide gel electrophoresis, respectively. An identical N
      terminal sequence up to 20 amino acid residues and similar amino acid
      compositions were obtained from both forms, but different C-terminal amino acids,
      leucine from G4(-1) and alanine from G4(-2), were released by carboxypeptidase Y.
      By in vitro incubation with a culture supernatant containing protease activity,
      G4(-1) was converted into G4(-2) without any loss of the amylase activity. It was
      concluded that G4(-2) was a product derived by the limited proteolysis of G4(-1),
      and that the proteolysis occurred in the C-terminal region of G4-1. G4-2 was more
      thermostable than G4(-1), and had a 20-fold higher Michaelis constant value for
      glycogen, which was 50 mg/ml against 2.3 mg/ml of G4(-1). G4(-1) adsorbed onto
      raw starch granules while G4(-2) did not.

PMID- 1368536
TI  - A new depsipeptide antibiotic, variapeptin.
AB  - A culture similar to Streptomyces variabilis was found to produce a novel cyclic
      hexadepsipeptide antibiotic named variapeptin. Variapeptin is structurally
      related to azinothricin, A83586C, and citropeptin. The antibiotic was active
      against Gram-positive bacteria and showed cytotoxic activity against mammalian
      cells.

PMID- 1368537
TI  - The reactivity of monoclonal antibodies against recombinant human superoxide
      dismutase.

PMID- 1368538
TI  - Action of levan fructotransferase of Arthrobacter ureafaciens on three
      oligosaccharides containing a bifurcose residue.

PMID- 1368539
TI  - A convenient method for the preparation of N-beta-alanyldopamine as a substrate
      of phenoloxidase.

PMID- 1368540
TI  - Inhibition of angiotensin-converting enzyme by synthetic peptide fragments of
      human kappa-casein.

PMID- 1368541
TI  - Cellulase production by Neurospora crassa: purification and characterization of
      cellulolytic enzymes.
AB  - In studies on cellulase production by the cell-1 mutant of Neurospora crassa,
      eight enzymes (three exoglucanases, four endoglucanases, and one beta
      glucosidase) were identified and characterized by gel filtration, ion exchange
      chromatography, and chromatofocusing. After purification, each of the proteins
      ran as a single band in polyacrylamide gel electrophoresis, using both native and
      denaturing gels. The molecular weights of the proteins were found to be between
      70,000 and 22,000 daltons, and all were glycosylated, with carbohydrate contents
      ranging between 5.6% and 36%.

PMID- 1368542
TI  - Magnetic aqueous two-phase separation in preparative applications.
AB  - Magnetic aqueous two-phase separation is a new technique to speed up the
      separation of aqueous two-phase systems (Anal. Biochem. 1987, 167, 331-339). It
      is based on the addition of magnetically susceptible material (e.g. 1-micron iron
      oxide particles) which induces rapid phase separation when a mixed system is
      placed in a magnetic field. The technique has been applied to a number of two
      phase systems. The time for phase separation was decreased by a factor of 5
      240,000, with the largest improvement for systems containing high concentrations
      of protein and for systems with viscous or nearly isopycnic phases. An apparatus
      for preparative multistage extraction with magnetic separation was constructed
      and tested on glycolytic enzymes present in a yeast extract using a
      dextran/Cibacron blue-polyethylene glycol system. The presence of iron oxide
      particles did not adversely affect the extracted enzymes. An electromagnet-based
      apparatus for continuous phase separation on a larger scale was also designed. A
      phase system containing crude dextran and unpurified cell homogenate was
      effectively processed. The apparatus also allowed effective separation when the
      phase containing iron oxide particles was only a small fraction (4%) of the total
      phase system.

PMID- 1368543
TI  - Expression and characterization of a tripartite fusion protein consisting of
      chimeric IgG-binding receptors and beta-galactosidase.
AB  - Using protein engineering, a tripartite fusion protein was constructed consisting
      of five IgG-binding regions of protein A from Staphylococcus aureus, two IgG
      binding regions of protein G from Streptococcus strain G148 and beta
      galactosidase from Escherichia coli. The resulting protein lacks the serum
      albumin binding regions of native protein G. The fusion protein, which is a
      tetramer of approximately 660 kDa, was designed as a tool for immunological
      assays taking advantage of its broad spectrum of antibody affinity. The gene was
      placed under control of two promoters, the PR promoter and the lac UV5 promoter
      and the expression from the two promoters was studied in a bioreactor. Induction
      of the PR promoter gave an intracellular product concentration corresponding to
      20% of the cell dry weight. By utilizing the properties of beta-galactosidase,
      the protein was purified by extraction in an aqueous two-phase system. The fusion
      protein was not proteolytically degraded during the cultivation and purification
      steps. The biological activity of all three parts of the protein was demonstrated
      with a competitive ELISA.

PMID- 1368544
TI  - A new depsipeptide antibiotic, citropeptin.
AB  - An actinomycete identified as Streptomyces flavidovirens was found to produce a
      new cyclic hexadepsipeptide antibiotic, designated citropeptin. Citropeptin
      showed antitumor activity against P388 murine leukemia.

PMID- 1368545
TI  - Separation of Asn-linked sialyloligosaccharides labeled with p-aminobenzoic acid
      ethyl ester by high-performance liquid chromatography.

PMID- 1368546
TI  - Effect of immunoglobulin production stimulating factors in foodstuffs on
      immunoglobulin production of human lymphocytes.

PMID- 1368547
TI  - Effects of phenyl compounds on proliferation and IgM production of human-human
      hybridoma HB4C5 cells cultured in serum-free medium.

PMID- 1368548
TI  - Inhibition of angiotensin-converting enzyme by synthetic peptide fragments of
      various beta-caseins.

PMID- 1368549
TI  - Action pattern of Aeromonas hydrophila chitinase on partially N-acetylated
      chitosan.
AB  - Oligosaccharides from the digestion of 34% N-acetylated chitosan by Aeromonas
      hydrophila chitinase were separated by CM-Sephadex C-25 column chromatography.
      Sugar compositions and the sequences of main oligosaccharides were identified
      through their N-acetylation, their cleavage with exo-glycosidases, and their
      degradation with nitrous acid. Hetero-chitooligosaccharides such as GlcN.GlcNAc,
      GlcN.GlcNAc.GlcNAc, GlcNAc.GlcN.GlcNAc, and GlcNAc.GlcN.GlcNAc.GlcNAc, together
      with GlcNAc and (GlcNAc)2, were detected. The structure of GlcN.GlcNAc was
      confirmed by the analysis with proton and carbon NMR spectroscopy. These studies
      indicate that Aeromonas hydrophila chitinase is more specific toward the N-acetyl
      beta-D-glucosaminidic bonds in partially N-acetylated chitosan.

PMID- 1368550
TI  - Purification and some properties of beta-fructofuranosidase I from Arthrobacter
      sp. K-1.
AB  - Arthrobacter sp. K-1, isolated from soil, produces beta-fructofuranosidase. This
      enzyme preparation was separated into three fractions (I, II, and III) by butyl
      Toyopearl 650 M column chromatography. The beta-fructofuranosidase I was purified
      to homogeneity by disc-electrophoresis after consecutive column chromatographies.
      The enzyme had a molecular weight of 52,000 by SDS-polyacrylamide gel
      electrophoresis and 51,000 by gel filtration with Ultrogel AcA 44, and an
      isoelectric point of 4.3. The enzyme was most active at pH 6.5-6.8 and at 55
      degrees C and stable up to 45 degrees C at pH 6.5 for 30 min of incubation, and
      from pH 5.5 to 10.0 at 40 degrees C in 2 hr of incubation. This enzyme hydrolyzed
      sucrose, erlose, raffinose, fructosylxyloside, neokestose, and stachyose at the
      relative velocities of 100, 75, 61, 59, 54, and 11, but hardly hydrolyzed 1
      kestose and nystose (less than 0.02).

PMID- 1368551
TI  - Purification and some properties of endo-1,3-beta-D-xylanase from Pseudomonas sp.
      PT-5.
AB  - An endo-1,3-beta-D-xylanase (1,3-beta-D-xylan xylanohydrolase, EC 3.2.1.32) was
      purified from the culture fluid of Pseudomonas sp. PT-5 by ammonium sulfate
      fractionation, DEAE-Sepharose CL-6B, Toyopearl HW-50S, and Butyl-Toyopearl 650 M
      column chromatography. The purified enzyme gave a single band on polyacrylamide
      gel disc electrophoresis and its molecular weight was 35,000 by SDS
      polyacrylamide gel electrophoresis. The enzyme was stable from pH 5.5 to 8.0 and
      had its maximum activity at pH 7.5. The enzyme rapidly reduced the viscosity of
      glycol beta-1,3-xylan solutions and produced xylose and xylooligosaccharides from
      seaweed beta-1,3-xylan. The enzyme activity was greatly inhibited by Hg2+, SDS,
      ethylenediamine tetraacetic acid (EDTA), and N-bromosuccinimide (NBS).

PMID- 1368552
TI  - Protoplast transfection of Lactobacillus casei by phage PL-1 DNA.
AB  - Polyethylene glycol (PEG) mediated transfection of Lactobacillus casei ATCC 27092
      protoplasts by phage PL-1 DNA was done. The protoplasts were obtained by
      treatment with purified PL-1 phage N-acetylmuramidase in the presence of citrate.
      Optimum conditions for transfection were 50% PEG 4,000, 15 micrograms protamine
      sulfate/ml, 0.15 M sucrose, and 10 mM MgSO4 in MR medium (pH 6.0). The extent of
      transfection was proportional to the amounts of DNA added, and the greatest
      efficiency of transfection after a 10-min incubation was about 3.3 x 10(5)
      PFU/micrograms DNA. The eclipse period of growth of progeny phages in the
      transfectants was 3 hr and the average burst size was 200.

PMID- 1368553
TI  - Expression of recombinant bovine beta-lactoglobulin in Escherichia coli.
AB  - Bovine beta-lactoglobulin A was expressed in Escherichia coli in its mature form.
      The gene was constructed using a cDNA clone which coded for amino acid residues
      Leu-11 to Ile-162 and a synthetic oligonucleotide coding for the initial 10 amino
      acids preceded by a translational start. The met-beta-lactoglobulin was expressed
      using a tac promoter vector, pTTQ18, and accounted for approximately 15% of the
      total cellular protein. The recombinant met-beta-lactoglobulin migrated with the
      same molecular weight as native beta-lactoglobulin A on SDS-PAGE. The majority of
      the met-beta-lactoglobulin produced was found in an insoluble form but could be
      solubilized using guanidine-HCl. The renatured preparation was greater than 80%
      pure and migrated similarly to purified beta-lactoglobulin A under nondenaturing
      conditions.

PMID- 1368554
TI  - Cloning and nucleotide sequence of the KHR killer gene of Saccharomyces
      cerevisiae.
AB  - The KHR gene cloned from a genomic library was on 4.7-kbp DNA fragment and was
      inserted into YCpG11 vector (KHR-YCp) and YEp vector (KHP-YEp). Transformants
      with KHR-YEp could secrete 3-4 times as much killer toxin into the media as the
      donor strain. The complete nucleotide sequence of the KHR gene was analyzed. It
      was found that the KHR gene consisted of 888 bp. It was suggested that this
      protein was processed before being secreted into the media, because its molecular
      mass presumed from the nucleotide sequence was larger than that of the mature
      killer toxin.

PMID- 1368555
TI  - Purification and some properties of dipeptidyl carboxypeptidase from Bacillus
      pumilus.
AB  - An intracellular protease from a bacterium, Bacillus pumilus HL721, was purified
      about 5000-fold by chromatography with a Q-Sepharose Fast Flow column, TSK-gel HA
      1000 glass column, and TSK-gel G3000SWXL column using Bz-Gly-Ala-Pro as a
      substrate. The enzyme was the most active at pH around 7.5 and stable from 4.5
      and 8.0. The enzyme activity was inhibited by Cu2+, EDTA, N-ethylmaleimide, o
      phenanthroline, and p-chloromercuribenzoic acid. The molecular weight of the
      enzyme was 155,000 by gel filtration. The enzyme removed dipeptide from the
      carboxyl end of some peptides used as substrates. From these results the enzyme
      seems to be a dipeptidyl carboxypeptidase.

PMID- 1368556
TI  - A practical test for in vitro evaluation of photosensitization: assessment with
      hematoporphyrin derivative (HPD).
AB  - A simple procedure is described for the determination of the photosensitizing
      potency of drugs, using three leukemic cell lines, two of lymphocytic origin,
      L1210 and P388 and one of erythroid type, Friend-745. The procedure allows one to
      investigate several aspects of the photosensitization properties of tested
      compounds such as cellular localization and direct (trypan blue exclusion) or
      delayed (clonogenicity) photomediated toxicities. The method was assessed using
      crude hematoporphyrin derivative (HPD) as well as dihematoporphyrin ether (DHE)
      or commercially available Photofrin II. Results were compared to those obtained
      with normal cells, e.g spleen lymphocytes and erythropoietic stem cells (CFU-e),
      and discussed in the light of the relative response of normal versus transformed
      cells.

PMID- 1368557
TI  - Recovery of Clostridium thermosulfurogenes produced beta-amylase by
      (hydroxypropyl)methylcellulose partition.
AB  - A procedure for recovering Clostridium thermosulfurogenes produced beta-amylase
      from fermentation broth by partition was developed. The partition was achieved by
      addition of ammonium sulfate to an aqueous solution of the enzyme with
      (hydroxypropyl)methylcellulose. The beta-amylase-containing pellet formed upon
      centrifugation could be redissolved and the polymer recovered by a second salt
      addition. The process was not dependent on polymer/enzyme solution pH, but it was
      affected by temperature, polymer nominal molecular weight and loading, and
      fermentation carbon source. Unlike more traditional aqueous-phase partitions,
      such as poly(ethylene glycol)/dextran, the current approach appeared to be
      biospecific.

PMID- 1368558
TI  - Identification and functional analysis of mammalian splicing factors.

PMID- 1368559
TI  - Lambda vectors for stable cloned gene expression.
AB  - The bacteriophage lambda offers a unique opportunity concurrently to minimize
      segregational instability in recombinant systems by chromosomal integration of
      the cloned gene and to achieve high cloned gene expression during an abortive
      lytic phase. Lysis leads approximately to a 100-fold amplification of the cloned
      gene. Cell lysis in the lytic state is blocked by a specific mutation (Sam),
      allowing the cell to maintain its integrity, and lambda DNA packaging is blocked
      by other mutations (Wam, Eam) that keep cloned genes open to transcription. In
      the presence of these mutations, extremely high levels of cloned beta
      galactosidase (more than 15% of total cell protein) have been obtained during
      abortive lysis from vectors found to be essentially 100% stable for over 75
      generations in the lysogenic phase.

PMID- 1368560
TI  - Soluble receptors for IL-1 and IL-4: biological activity and therapeutic
      potential.
AB  - Cytokine research has yielded a range of products which have now reached the
      stage of clinical trials and a plethora of novel therapeutics may be expected.
      Recently, cytokine receptors have also become an area of intensive research.
      Preliminary results indicate that recombinant soluble receptors can interfere
      with the biological functions of cytokines and thus may be appropriate for the
      treatment of certain pathological conditions where cytokine activity needs to be
      modulated.

PMID- 1368561
TI  - Mechanism for the bitter tasting potency of peptides using O-aminoacyl sugars as
      model compounds.
AB  - In order to study the role of hydrophobicity in bitter peptides, several O
      aminoacyl sugars, in which amino acids or peptides were attached to the 2- and 3
      position of methyl alpha-D-glucopyranoside, were synthesized and sensory analyses
      were carried out. It was found that the bitterness increased as the
      hydrophobicity of compounds increased, implying that the bitterness receptor
      recognizes the hydrophobicity of bitter peptides. A structure for the bitterness
      receptor is also discussed.

PMID- 1368562
TI  - Immobilization of fatty acid synthetase from Mycobacterium smegmatis by radiation
      induced polymerization.
AB  - Fatty acid synthetase of Type I from Mycobacterium smegmatis was immobilized by
      radiation-induced polymerization of 2-hydroxyethyl methacrylate (HEMA) in the
      presence of trimethylolpropane trimethacrylate (TMPTMA). The stability of
      immobilized synthetase toward low ionic strength increased in comparison with the
      free form, but the stabilities of immobilized preparations assessed by pH and
      temperature were identical to those of the free form. The apparent Km of
      immobilized enzyme for acetyl-CoA and malonyl-CoA were both 6 microM, essentially
      the same as those of the free form; acetyl-CoA, 5 microM and malonyl-CoA, 6
      microM.

PMID- 1368563
TI  - Continuous synthesis of a tripeptide by successive condensation and
      transesterification catalyzed by two immobilized proteinases in organic solvent.
AB  - The tripeptide Z-GlyPheLeuNH2 was continuously synthesized in a high yield from
      three amino acid derivatives, Z-Gly, PheOMe, and LeuNH2, by immobilized
      thermolysin (IMT) and immobilized alpha-chymotrypsin (IMC) in an organic solvent,
      ethyl acetate. The optimal conditions for the synthesis of Z-GlyPheOMe were
      established theoretically. The yield of Z-GlyPheOMe with IMT in ethyl acetate
      saturated with buffer was more than 88% after continuous synthesis for 116 hr.
      The optimal conditions for the synthesis of Z-GlyPheLeuNH2 from Z-GlyPheOMe and
      LeuNH2 by IMC through transesterification was established in batch reaction
      experiments. When the concentration of water in the reaction solution was 17-20
      microliters/ml, the activity of IMC was highest. The equilibrium between the
      water concentration in the reaction solution and that in the resin used for
      enzyme immobilization depended on the resin and was not affected by the presence
      of the enzyme immobilized. Z-GlyPheLeuNH2 was synthesized from Z-GlyPheOMe and
      LeuNH2 with a yield of 100%, by continuous reaction for 160 hr. The reactor for
      synthesis of this tripeptide was efficient and stable because of the use of
      transesterification and the choice of an appropriate organic solvent. The series
      plug-flow reactor was successfully operated for 220 hr with a yield of more than
      80%. The residual activity of IMT was 94% and that of IMC was 100%.

PMID- 1368564
TI  - Cloning and expression of the creatinase gene from Flavobacterium sp. U-188 in
      Escherichia coli.
AB  - The gene coding for creatinase (creatine amidinohydrolase, EC 3.5.3.3) was
      isolated from Flavobacterium sp. U-188. The primary structure of creatinase
      deduced from the nucleotide sequence showed a protein (molecular weight, 42, 651)
      composed of 378 amino acids. The creatinase gene was over-expressed in
      Escherichia coli under the control of the lac promoter and the amount of this
      enzyme was over 20% of the soluble protein in the cell.

PMID- 1368565
TI  - Leucine dehydrogenase from Corynebacterium pseudodiphtheriticum: purification and
      characterization.
AB  - Leucine dehydrogenase [EC 1.4.1.9] was purified to homogeneity from
      Corynebacterium pseudodiphtheriticum ICR 2210. The enzyme consisted of a single
      polypeptide with a molecular weight of about 34,000. Stepwise Edman degradation
      provided the N-terminal sequence of the first 24 amino acids, and
      carboxypeptidase Y digestion provided the C-terminal sequence of the last 2 amino
      acids. Although the enzyme catalyzed the reversible deamination of various
      branched-chain L-amino acids, L-valine was the best substrate for oxidative
      deamination at pH 10.9 and the saturated concentration. The enzyme, however, had
      higher reactivity for L-leucine, and the kcat/Km value for L-leucine was higher
      than that for L-valine. The enzyme required NAD+ as a natural coenzyme. The NAD+
      analogs 3-acetylpyridine-NAD+ and deamino-NAD+ were much better coenzymes than
      NAD+. The enzyme activity was significantly reduced by sulfhydryl reagents and
      pyridoxal 5'-phosphate. D-Enantiomers of the substrate amino acids competitively
      inhibited the oxidation of L-valine.

PMID- 1368566
TI  - Chromosomal transformation in Saccharomyces cerevisiae with DNA isolated by pulse
      field gel electrophoresis.
AB  - We isolated and purified yeast chromosome DNA molecules using pulse field gel
      electrophoresis (PFG). The isolated DNA had nearly the same size as the native
      chromosomal DNA on PFG. We could directly transform Saccharomyces cerevisiae
      yeasts with it, and obtain transformants that were selected by complementation of
      several markers. They had new chromosome DNA bands observed on PFG. The new
      chromosome was very stable during mitosis and mating processes, and each of the
      three homologous chromosomes in the derivative zygotes of transformants was
      separated equally in daughter cells.

PMID- 1368567
TI  - Solid-phase synthesis and crystallization of monellin, an intensely sweet
      protein.
AB  - Monellin, a sweet protein, consists of two noncovalently associated polypeptide
      chains, the A chain of 44 amino acid residues and the B chain of 50 residues. Two
      different primary structures have been reported for each of the A and B chains.
      The A and B chains corresponding to one of the reported monellin structures were
      synthesized by the stepwise solid-phase method using the Fmoc strategy in overall
      yields of 14.1% and 5.6%, respectively. The characterization of the synthetic
      peptides by HPLC, FAB-MS, amino acid analysis and sequencing fully supported the
      expected structures. The individual synthetic A and B chains were not sweet.
      Combination of the two chains, and subsequent HPLC purification gave monellin in
      a yield of 53.9%. The synthetic monellin had a distinct, lingering sweet taste
      (4000 times sweeter than sucrose) and was crystallized by a vapor diffusion
      method. The synthetic product was identical to natural monellin by HPLC, but not
      by tryptic mapping. These results indicate that the reported structure for
      monellin differs slightly from that of natural monellin.

PMID- 1368568
TI  - Syntheses and biological activities of (+/-)-streptovitacin A and E-73.
AB  - (+/-)-Streptovitacin A (1) and its stereoisomers were synthesized by an aldol
      reaction of (+/-)-2,4-dimethyl-4-trimethylsiloxy-1-cyclohexanones (4b and 9) with
      4-(2-oxoethyl)-2,6-piperidinedione (5). E-72 (2) was derived from synthetic 1.
      (+/-)-1 showed moderate growth inhibition against fungi and lettuce seeds.

PMID- 1368569
TI  - Transformation of Lactobacillus helveticus subsp. jugurti with plasmid pLHR by
      electroporation.
AB  - Lactobacillus helveticus subsp. jugurti was transformed with plasmid, pLHR (8.5
      kilobases), by electroporation. The plasmid, pLHR, consists of a cryptic plasmid,
      pLJ1, from L. helveticus subsp. jugurti, the Escherichia coli vector pBR329, and
      the erythromycin resistance gene of pAM beta 1 from Enterococcus faecalis.
      Maximum transformation efficiency of 1.3 x 10(4) transformants per microgram of
      DNA was obtained by exposure to a pulse with an exponential decay waveform at 4
      kV/cm with 25 microF capacitance. The presence of glycine in the growth medium
      was essential for transformation. Plasmid DNA isolated from transformants had not
      undergone detectable rearrangements or deletions. In addition, it was found that
      L. helveticus subsp. jugurti has a restriction and modification system.

PMID- 1368570
TI  - Identification of O-alpha-D-glucopyranosyluronate-(1----2)-D-galactose isolated
      from the acidic polysaccharide of Fusarium sp. M7-1.

PMID- 1368571
TI  - A new cDNA clone relating to larger molecular species of rat insulin-like growth
      factor-I mRNA.
AB  - A new cDNA clone for rat IGF-I mRNA was obtained. The cDNA contained a new base
      sequence as cDNA in the 3' region. The sequence coincided with a part of the
      sequence reported earlier by Shimatsu and Rotwein in exon 5 of the rat IGF-I
      gene. The presence of this cDNA proved the previous suggestion to be true that
      the size heterogeneity of IGF-I mRNA is primarily due to the heterogeneity of the
      3'-untranslated region.

PMID- 1368572
TI  - Morphological changes of tumor cells caused by macrophages treated with lignin
      derivatives.

PMID- 1368573
TI  - Molecular cloning, nucleotide sequence and expression in Escherichia coli of the
      beta-cyclodextrin glycosyltransferase gene from Bacillus circulans strain no. 8.
AB  - The beta-cyclodextrin glycosyltransferase (beta-CGTase) gene was isolated from a
      lambda-library prepared from Bacillus circulans strain no. 8. It was subcloned
      into plasmid pTZ and expressed by its endogenous regulatory sequences in
      Escherichia coli JM 103. The structural gene was sequenced and showed an open
      reading frame for a polypeptide of 718 amino acid residues. The recombinant beta
      CGTase had the same enzymatic properties as the extracellular CGTase (684 amino
      acid residues, corresponding to a mol. wt. of 74416) produced by B. circulans
      strain no. 8. The amino acid sequence showed the highest homology (74.6%
      identical amino acids) with the CGTase of B. circulans strain F-2, which had been
      erroneously described as an amylase. The homology with the enzyme from the
      alkalophilic Bacillus sp. strain no. 1011 was 71.4%. The amino acid sequence
      derived will be used for elucidating the three-dimensional structure of the
      enzyme.

PMID- 1368574
TI  - Synthesis and biological activities of griseofulvin analogs.
AB  - In order to elucidate the structure-activity relationship of griseofulvin (1),
      (+/-)-6-demethyl analog (3), 2-demethoxy-6-demethyldihydro analog (4), (+/-)
      dechloro-6-ethyl analog (5), (+/-)-dechloro-6-epi-ethyl analog (6), (+/-)6-ethyl
      analog (7) and (+/-)-6-epi-ethyl analog (8) were synthesized by a Diels-Alder
      cycloaddition of alkylidene ketones (16, 17 18, 19 and 20) with modified 1,3
      butadienes (21 or 22). Their biological activities were examined against fungi.

PMID- 1368575
TI  - Complete amino acid sequence of the sweet protein monellin.
AB  - The sweet protein monellin consists of two noncovalently associated polypeptide
      chains, the A chain of 44 amino acid residues and the B chain of 50 residues. Two
      different primary structures have been reported for each of these chains. The
      complete amino acid sequence of monellin was determined by a combination of FAB-
      and ESI-mass spectrometry, and by automatic Edman degradation.

PMID- 1368576
TI  - Evidence of introduction by molecular cloning of artificial inverted sequence at
      the 5' terminus of the sense strand of rat insulin-like growth factor-I cDNA.
AB  - A cDNA of insulin-like growth factor (IGF)-I mRNA was obtained from a rat liver
      cDNA library. This cDNA contained a 5' terminal sequence of 48 base pairs
      complementary to a sequence in the 3' terminal region (an inverted repeat
      sequence) except for one nucleotide insertion in the 3' region. Base sequence
      analysis of this cDNA, northern blot analysis of rat liver mRNA using a probe
      specific to 5' region of cDNA, base sequence studies of the 5' upstream region of
      a clone of the rat IGF-I gene, and some other studies suggested strongly that the
      inverted repeat sequence of the IGF-I cDNA used was introduced artificially
      during preparation of the cDNA library.

PMID- 1368577
TI  - A cis-acting locus needed for stable maintenance of the yeast plasmid pSB3.
AB  - The Zygosaccharomyces rouxii plasmid pSB3 is one of the yeast plasmids resembling
      2-microns DNA. The presence of a cis-acting locus needed for stable maintenance
      of pSB3 has been expected by analogy with the functions encoded by other yeast
      plasmids such as 2-microns DNA and pSR1. We found such a locus and designated it
      STB-SB3. The STB-SB3 locus was delimited within 371 bp in a unique region of
      pSB3. This region is included in the plasmid region where no transcript was
      detected. No prominent feature of the nucleotide sequence was found in this
      region except for a direct repeat with 65% homology consisting of 27 bp and 29
      bp. This is in clear contrast with the structure of the STB locus of 2-microns
      DNA which has five and a half tandem repeats consisting of a highly homologous 62
      bp sequence. By analyzing the sites hypersensitive to nucleases using partially
      purified nuclei containing pSB3, the STB-SB3 locus was found not to be tightly
      folded into a nucleosome structure.

PMID- 1368578
TI  - The amino acid sequence of Lady Amherst's pheasant (Chrysolophus amherstiae) and
      golden pheasant (Chrysolophus pictus) egg-white lysozymes.
AB  - The amino acids of Lady Amherst's pheasant and golden pheasant egg-white
      lysozymes have been sequenced. The carboxymethylated lysozymes were digested with
      trypsin followed by sequencing of the tryptic peptides. Lady Amherst's pheasant
      lysozyme proved to consist of 129 amino acid residues, and a relative molecular
      mass of 14,423 Da was calculated. This lysozyme had 6 amino acids substitutions
      when compared with hen egg-white lysozyme: Phe3 to Tyr, His15 to Leu, Gln41 to
      His, Asn77 to His, Gln 121 to Asn, and a newly found substitution of Ile124 to
      Thr. The amino acid sequence of golden pheasant lysozyme was identical to that of
      Lady Amherst's phesant lysozyme. The phylogenetic tree constructured by the
      comparison of amino acid sequences of phasianoid birds lysozymes revealed a
      minimum genetic distance between these pheasants and the turkey-peafowl group.

PMID- 1368579
TI  - Enhancing effect of malondialdehyde modification on the mouse IgE response to
      protein antigens.
AB  - To investigate the immunochemical properties of proteins reacted with
      malondialdehyde (MDA), which is a major degradation product of lipid oxidation,
      the antibody responses of mice immunized with MDA-modified bovine serum albumin
      (BSA) were examined. The specific IgE response to MDA-BSA was 4 to 8 times higher
      than that to native BSA, suggesting that the specific IgE antibody response to
      MDA-modified protein was enhanced by MDA bound to the surface of the protein. The
      antibodies to MDA-BSA did not distinguish the modified protein from the native
      one, and the antibodies raised against the modified proteins were not specific
      for the MDA portion but were for the carrier proteins.

PMID- 1368580
TI  - Molecular cloning and nucleotide sequence of the aminopeptidase T gene of Thermus
      aquaticus YT-1 and its high-level expression in Escherichia coli.
AB  - Aminopeptidase T (AP-T) is a metallo-dependent dimeric enzyme of Thermus
      aquaticus YT-1, an extremely thermophilic bacterium. We cloned the AP-T gene from
      T. aquaticus YT-1 into Escherichia coli using a synthetic oligonucleotide as a
      hybridization probe. The nucleotide sequence of the AP-T gene was found to encode
      408 amino acid residues with GTG as a start codon. The molecular weight was
      calculated to be 44,820. The AP-T was overproduced in E. coli (about 5% of total
      soluble protein) when the start codon of the gene was changed from GTG to ATG,
      and the gene was downstream from the tac promoter. The AP-T expressed in E. coli
      was heat stable and easily purified by heat treatment (80 degrees C, 30 min). The
      N-terminal amino acid sequence of AP-T showed similarity with that of
      aminopeptidase II from Bacillus stearothermophilus.

PMID- 1368581
TI  - Ren-2 as well as Ren-1 renin exists in the kidney and plasma of a two-renin gene
      mouse.
AB  - Ren-1 renin is synthesized in the kidney of every mouse. Ren-2 renin has been
      observed in the submandibular gland (SMG) of male mice carrying two renin genes.
      However, it is not known if Ren-2 renin is in the kidney and blood of the two
      renin gene mice. In this study, a direct ELISA for Ren-2 renin (SMG renin) was
      established by a sandwich method. This ELISA could measure the Ren-2 active renin
      in the range from 1 to 100 ng and distinguish Ren-2 active from not only Ren-1
      renin but also Ren-2 prorenin. By a combination of this assay system and
      conventional methods, the pro-form as well as the active form of Ren-2 renin was
      found in the kidney and plasma of male AKR mice carrying two-renin genes.

PMID- 1368582
TI  - Identity of aabomycin A with venturicidins.

PMID- 1368583
TI  - Molecular cloning of the xylA gene encoding xylose isomerase from Streptomyces
      griseofuscus S-41: primary structure of the gene and its product.

PMID- 1368584
TI  - Amino acid sequence of pheromone biosynthesis activating neuropeptide-II (PBAN
      II) of the silkmoth, Bombyx mori.

PMID- 1368585
TI  - Flow injection analysis in bioprocess control.

PMID- 1368586
TI  - Allergy: big market, big risks.

PMID- 1368587
TI  - Stabilization of tumor antigens by chemical modification with diethyl
      pyrocarbonate.
AB  - C3H mice were immunized with MH134 tumors modified with two different chemicals,
      DEPC and TNBS, and the tumor-neutralizing activities of the spleen cells were
      examined after separating the cells by a Nylon-wool column, plastic dish, or
      treatment with specific antibodies (anti-mouse IgG and anti-mouse theta sera).
      The effector cells induced in mice by immunization with TNBS-treated tumors were
      T cells. In contrast, in the case of tumors modified with DEPC, macrophages were
      the major effector cells. The effects of chemical modification on the
      solubilization of cell surface proteins was also examined. DEPC inhibited
      solubilization of specific proteins from tumor cell surfaces, while TNBS did not
      have such an effect on the solubilization of proteins. These results indicate
      that the antitumor response in mice primed with DEPC-modified tumor is different
      from the case of TNBS-modified tumors, and that the immunological significance of
      chemical modification with DEPC is supposedly due to the stabilization of
      antigenic proteins on the tumor cell surface.

PMID- 1368588
TI  - N-terminal extension of sweet peptides in relation to the structural features of
      peptide sweeteners.
AB  - Sweet aspartyl di- and tripeptide esters were extended toward the N-terminus in
      relation to the structural features of sweet peptides. The sweet peptides were
      designed on the basis of the receptor site model. It was found that an extension
      of the sweet aspartyl dipeptide esters by adding a small D-amino acid residue
      mostly gave sweet compounds (e.g., D-Ala-L-Asp-D-Ala-OMe), although this
      significantly decreased their sweetness potencies. Further extension at the N
      terminus of the extended sweet tripeptide esters to yield the tetrapeptide esters
      resulted in a loss of the sweet taste. The N-terminal extension of sweet aspartyl
      tripeptide esters resulted in faintly sweet or nonsweet tetrapeptide esters.
      Interestingly, an analogous extension at the N-terminus of the sweet aminomalonyl
      dipeptide esters gave bitter compounds (e.g., D-Ala-DL-Ama-L-Phe-OMe). These
      results indicate that the receptor has a small space that can accomodate an
      additional small D-amino acid residue at the site facing the N-terminus of sweet
      aspartyl dipeptide esters.

PMID- 1368589
TI  - FAB-MS/MS spectrometry in determining the primary structure of gamma-glutamyl
      containing peptides.
AB  - Positive fast atom bombardment tandem mass spectrometry (FAB-MS/MS) was applied
      for peptide sequencing, particularly for determining the gamma glutamyl linkage
      involved in metal-binding peptides such as Cadystin (gamma EC)3G = Cadystin A and
      Cadystin (gamma EC)2G = Cadystin B (MW 771 and 539, respectively). The
      fragmentation patterns between the natural gamma glutamyl peptide and the
      synthetic alpha glutamyl one were clearly distinguishable. FAB-MS/MS was proved
      to be a good method for determining these peptides, since it needed no chemical
      degradation and only a small amount of the peptide was needed for determination.

PMID- 1368590
TI  - Occurrence of free O-phosphoserine and O-phosphothreonine in porcine liver.
AB  - The occurrence of free O-phosphoserine and O-phosphothreonine in porcine liver is
      demonstrated. These amino acids were separated from the tissue extracts by anion-
      and cation-exchange chromatography and thin-layer chromatography, and were
      identified by gas chromatography with flame photometric detection and gas
      chromatography-mass spectrometry. The contents of O-phosphoserine and O
      phosphothreonine in the liver were estimated to be 377 +/- 13 ng/g and 115 +/- 2
      ng/g, respectively.

PMID- 1368591
TI  - High-level secretion of a Rhizopus niveus aspartic proteinase in Saccharomyces
      cerevisiae.
AB  - The gene encoding an extracellular Rhizopus niveus aspartic proteinase I (RNAP-I)
      was introduced into Saccharomyces cerevisiae. The yeast cell carrying a plasmid
      containing the intact RNAP-I gene under the control of the glyceraldehyde 3
      phosphate dehydrogenase (GAPDH) gene promoter of S. cerevisiae did not synthesize
      RNAP-I at all. On the other hand, when the intron of the RNAP-I gene had been
      removed from the gene in the plasmid, the cell secreted RNAP-I with high
      efficiency. Processing of the pro-sequence occurred at the same region of the pro
      enzyme during cultivation as observed in the culture of R. niveus. Moreover, the
      promoter and the terminator of the original RNAP-I gene were found to be weakly
      functional in the yeast cell with respect to expression of the intronless RNAP-I
      gene, although the initiation and termination sites were heterogeneous. The
      effects of vector-types on the extracellular production of RNAP-I were also
      investigated.

PMID- 1368592
TI  - Proliferation-stimulating activity of detergents having oleic acid residues in
      serum-free culture of mammalian cells.

PMID- 1368593
TI  - Direct sequencing of flanking regions of a transgene amplified by inverted PCR.

PMID- 1368594
TI  - Syntheses and biological activities of photolabile indolactam derivatives; new
      probes for the receptor analysis of tumor promoters.

PMID- 1368596
TI  - A novel isolation method for hen egg yolk antibody, "IgY".
AB  - A method for isolation of egg yolk immunoglobulin, IgG, a livetin protein, was
      investigated. Several natural gums (carrageenan and xanthan gum) were found to be
      effective for removal of yolk lipoprotein as a precipitate. The effect was
      pronounced with lambda-carrageenan and the lipid content in the supernatant after
      removal of the resulting precipitate was less than 0.4% of that of egg yolk. IgY
      remained in this supernatant, with a yield of 86%, and was isolated by
      chromatography on a column of DEAE-Sephacel followed by salting-out with sodium
      sulfate. IgY thus isolated was almost pure (98%) and the yield was 70 to 100 mg
      per egg.

PMID- 1368595
TI  - Purification of a membrane glycoprotein with an inositol-containing phospholipid
      anchor from Dictyostelium discoideum.
AB  - Large-scale purification of a Dictyostelium discoideum cell surface glycoprotein,
      which is anchored in the membrane via a glycosylphosphatidylinositol (GPI)
      moiety, is described. The purification protocol involved four steps: separation
      of crude cell membranes by low-speed centrifugation, delipidization of these
      membranes using acetone, extraction of the membrane proteins using the detergent
      Octyl beta-D-thioglucopyranoside (OTP), and purification of a specific membrane
      protein by monoclonal antibody immunoaffinity chromatography. The protein
      purified, PsA (prespore-specific antigen), is a developmentally regulated
      membrane glycoprotein found on a subset of cells from the cellular slime mould,
      D. discoideum. The protocol provides an efficient, economical, and technically
      simple way to purify GPI proteins in sufficient quantities for structural and
      functional studies. PsA was recovered at a yield of about 60%; with a purity of
      97%, the extraction of 1 x 10(10) cells (1.1 g dry weight) yielded about 0.5 mg
      PsA glycoprotein. Techniques are described for growing kilogram quantities of D.
      discoideum cells in stainless steel trays at little cost. D. discoideum has
      considerable potential as a novel expression system for the production of foreign
      membrane-associated proteins. The purification strategy provides a means of
      purifying other GPI proteins, including those produced by protein engineering
      techniques.

PMID- 1368597
TI  - Identification and characterization of a thermolabile antigen (TLAa, enolase) in
      Saccharomyces cerevisiae.
AB  - Five kinds of proteins of Saccharomyces cerevisiae were recently purified to a
      homogeneous state and identified as yeast cell surface antigens (TLAa, TLAb,
      TLAc, TLAd, and TLAe), but their physiological functions remained uncertain. In
      this paper, TLAa was identified as a yeast enolase (EC 4.2.1.11) from the
      following evidence: (1) molecular weights and amino acid compositions of both
      proteins were similar, (2) the N-terminal 22 amino acid sequences of both
      proteins were the same (3), TLAa had enolase activity, and (4) the authentic
      yeast enolase gave a positive reaction with anti-TLAa serum in the Ouchterlony
      immunodiffusion test and the immunoblotting test. Two isoproteins of TLAa
      (enolase) were separated by non-denatured polyacrylamide gel electrophoresis and
      detected by immunoblotting with anti-TLAa serum. The contents of the two
      isoproteins varied depending on the following culture conditions: glucose
      starvation, growth in the presence of non-fermentable carbon sources, and growth
      in media containing sodium chloride and 2-deoxyglucose. The contents did not
      vary, however, with heat shock treatment or with growth in media containing
      sodium azide, tunicamycin, or sorbitol. These results showed that TLAa was a
      cytoplasmic antigen, and that its synthesis was regulated by some environmental
      stresses.

PMID- 1368598
TI  - Structure of di-O-alpha-maltosyl cyclodextrins produced from alpha
      maltosylfluoride and cyclodextrins.
AB  - The structures of di-O-alpha-maltosyl beta-cyclodextrins ((G2)2-beta-CDs), which
      were produced from alpha-maltosylfluoride (alpha-G2F) and cyclodextrin (CD) by
      the transfer action of debranching enzymes, were examined by the enzymic method
      using Bacillus subtilis saccharifying alpha-amylase (BSA). (G2)2-beta-CD was
      converted to (G1)2-beta-CD by treatment with glucoamylase before the examination.
      BSA completely hydrolyzed (G1)2-beta-CD to produce glucose, 6(3)-O-alpha
      glucosylmaltotriose, and 6(3),6(5)-di-O-alpha-glucosyl maltopentaose. (G2)2-beta
      CD was the mixture of 6A,6C-di-O-alpha-maltosyl beta-CD and 6A,6D-di-O-alpha
      maltosyl beta-CD. The ratio of A,C/A,D in (G2)2-beta-CD synthesized with
      Pseudomonas isoamylase and Aerobacter pullulanase were 40:60-45:55 and 30:70,
      respectively. The content of 6A,6C-di-O-alpha-maltosyl gamma-CD in (G2)2-gamma-CD
      synthesized by isoamylase was about 35%.

PMID- 1368599
TI  - Isolation of restriction-reduced mutants from Streptomyces.
AB  - Restriction-reduced mutants were isolated from Streptomyces rosa subsp. notoensis
      KA301 and S. tanashiensis strain Kala which produce the benzoisochromanequinone
      antibiotics nanaomycin and kalafungin, respectively. The mutants of S. rosa,
      which can be transformed with a multi-copy plasmid and in which the actinophage
      Pa16 can propagate, were selected. They were transformed with a single-copy
      plasmid propagated in S. lividans TK24, and with its modified plasmid propagated
      in the mutant at higher efficiency. The mutants of S. tanashiensis were selected
      by their capability to be transformed with a multi-copy plasmid. The efficiency
      of transformation with a single-copy plasmid propagated in S. lividans TK24 was
      low, but was much increased by heating the protoplasts at 42 degrees C for 15 min
      prior to the transformation. These mutants derived from both strains probably
      lack at least one of their restriction systems.

PMID- 1368600
TI  - Cloning and expression of endo-beta-1,3-glucanase gene from Flavobacterium
      dormitator in Escherichia coli and characterization of the gene product.
AB  - The beta-1,3-glucanase (1,3-beta-D-glucan glucanohydrolase, EC 3.2.1.6) gene from
      Flavobacterium dormitator var. glucanolyticae was cloned into Escherichia coli
      C600 with a vector plasmid, pBR322. The E. coli cells carrying a recombinant
      plasmid, pKU beta G1 (8.2 kb), showed a high beta-1,3-glucanase activity and a
      lytic activity on viable yeast cells. These activities were found in the
      periplasmic space of E. coli clone cells. Southern hybridization analysis showed
      that the cloned gene was derived from F. dormitator chromosomal DNA. The gene
      products were purified from the periplasmic fraction of E. coli by ammonium
      sulfate fractionation and ion-exchange chromatography. The purified enzymes were
      demonstrated to be identical with a lytic endo-beta-1,3-glucanase II and a
      nonlytic endo-beta-1,3-glucanase I from F. dormitator from their enzymological
      and immunological properties. In the E. coli cells, endo-beta-1,3-glucanase I was
      also formed by a proteolytic digestion of endo-beta-1,3-glucanase II during the
      cultivation as in F. dormitator. Thus, the only endo-beta-1,3-glucanase II was
      coded for in the cloned gene.

PMID- 1368601
TI  - Hyper-heterogeneity of the N-terminus of recombinant BSF-2/IL-6 produced in CHO
      and NIH3T3 cells.
AB  - Recombinant human BSF-2 (B cell stimulatory factor 2/Interleukin 6; IL-6)
      proteins were purified from CHO and NIH3T3 cell cultures and characterized. The
      lectin binding patterns suggested that the proteins have N-linked
      oligosaccharide(s) with tri-antennary structure of bisecting GlcNAc. Their N
      termini were highly heterogeneous; at least five closely related N-termini were
      detected. This N-terminal heterogeneity was not generated in the cell culture
      because no processing activity was found in the culture medium.

PMID- 1368602
TI  - The restriction endonuclease GceinI of Gluconobacter cerinus IFO 3260, an
      isoschizomer of BamHI, has a monomeric structure.

PMID- 1368603
TI  - Molecular cloning of the glucoamylase gene of Aspergillus shirousami and its
      expression in Aspergillus oryzae.
AB  - The glucoamylase enzyme (GAase) gene from Aspergillus shirousami was cloned and
      sequenced from genomic and cDNA libraries. The genomic gene was located in the
      5.4 kb EcoRI fragment. The deduced amino acid sequence of GAase contained 639
      amino acid residues with a relative molecular mass of approximately 68,000
      daltons (non-glycosylated form). The genomic gene of A. shirousami GAase was
      introduced into Aspergillus oryzae. These transformants had increased GAase and
      raw starch degradation (RSD) activity in culture media and in rice-koji extracts.
      Analysis by Southern, Northern, SDS-PAGE, and Western blot techniques confirmed
      the foreign gene was correctly transcribed, translated, and expressed in A.
      oryzae.

PMID- 1368604
TI  - Isolation and some properties of acid phosphatase-1(1) from tomato leaves.
AB  - An isozyme of acid phosphatase-1, acid phosphatase-1(1), was purified from the
      leaves of tomato (Lycopersicon esculentum) to homogeneity and characterized. The
      purified enzyme was homogeneous on polyacrylamide gel electrophoresis with or
      without sodium dodecyl sulfate. The gel filtration analysis showed that the
      native molecule had a relative molecular mass of about 61 kilodaltons (kDa). The
      relative molecular mass of the subunit on gel electrophoresis with sodium dodecyl
      sulfate was about 32 kDa, indicating that the native form of the enzyme was a
      homodimer. It was suggested by periodic acid-Schiff staining on the gel that the
      enzyme was a glycoprotein. The Km for p-nitrophenylphosphate was 2.9 x 10(-3) M.
      The enzyme had a pH optimum of 4.5 in 0.15 M potassium acetate buffer with p
      nitrophenylphosphate as a substrate. This enzyme was activated by divalent metal
      ions, such as Zn2+, Mg2+, and Mn2+. The N-terminal amino acids were sequenced
      after the purified enzyme was treated with pyroglutamylpeptidase. It was
      suggested that the N-terminal amino acid was pyroglutamate.

PMID- 1368605
TI  - Preparation of polyclonal antibodies to an anti-tumor (1----3)-beta-D-glucan,
      schizophyllan.
AB  - Antibodies against Schizophyllan (SPG) or SPG conjugated with bovine serum
      albumin (BSA) were raised in rabbits by multiple subcutaneous immunization. The
      titer of SPG-reactive antibodies in the antiserum to SPG-BSA conjugate was
      significantly higher than in the antiserum to SPG as assessed by enzyme-linked
      immunosorbent assay (ELISA). The SPG-reactive antibodies purified by affinity
      chromatography using a Protein A-Sepharose CL-4B column interacted with the SPG
      BSA conjugate spotted on a nitrocellulose membrane filter in a dose-dependent
      manner, but the anti-SPG antibodies did not interact with BSA. Immunocytochemical
      staining has also shown that the anti-SPG antibodies reacted with SPG taken up by
      mouse peritoneal macrophages.

PMID- 1368606
TI  - The enzymatic and molecular characteristics of Saccharomycopsis alpha-amylase
      secreted from Saccharomyces cerevisiae.
AB  - The Saccharomycopsis fibuligera alpha-amylase (Sfamy) gene was expressed in
      Saccharomyces cerevisiae. The highest productivity of Sfamy was 70 mg per liter
      of culture broth. We purified Sfamy from the culture broth and identified the NH2
      terminal primary sequence. This sequence suggests that the Sfamy gene product is
      synthesized as a pre-pro-precursor, and the pro-sequence is cleaved after a Lys
      Arg sequence with the calpain-like endopeptidase encode by the KEX2 gene,
      resulting in mature Sfamy protein composed of 468 amino acids. Furthermore, the
      enzyme Sfamy is a glycoprotein in which one N-linked sugar chain containing
      mannose residues is attached to the Asn residue at the 198 position. The Km and
      kcat values were 1.1 x 10(-4) M and 1.4 x 10(2) sec-1, respectively, using
      amylose (the degree of polymerization n = 18) as a substrate. Moreover, the
      secondary structure, the location of the secondary elements including alpha
      helix, beta-sheet, and loop, and tertiary structure were predicted theoretically
      on the basis of the molecular structure of Aspergillus oryzae alpha-amylase. Taka
      amylase A (TAA). These results indicate that Sfamy protein is composed of main
      (M) and C-terminal (C) domains. The molecular structure of M domain closely
      resembles that of TAA, but the C domain appears to be more compact than that of
      TAA because of deletions at three regions forming turns and one region forming
      alpha-helix.

PMID- 1368607
TI  - Quantification of physical and cyto-physiological conditions for the
      electrofusion of Saccharomyces cerevisiae.
AB  - Various conditions for obtaining hybrids of the auxotrophic mutants SH1509 and
      SH1512 of Saccharomyces cerevisiae by electrofusion were investigated. An AC
      field of 400 Vp/cm and a DC field of 2 square pulses (7 kV/cm; 60 microsec each)
      at an interval of 0.5 sec were effective. Treatment with 0.2 (SH1509) or 1.0
      mg/ml (SH1512) Zymolyase for 1 or 1.5 hr was essential. As to the molarity of the
      osmotic stabilizer (sorbitol), the hybrid yield peaked at 0.6 M. The presence of
      CaCl2 (up to 0.4 mM) or 0.1 mM CaCl2 with 0.1 mM MgCl2 enhanced the yield. The
      temperature of the spheroplast suspension during pulsations also affected the
      yield, the most suitable temperature being 28 degrees C.

PMID- 1368608
TI  - Cloning and nucleotide sequence of an esterase gene from Pseudomonas fluorescens
      and expression of the gene in Escherichia coli.
AB  - A gene coding for a novel esterase of Pseudomonas fluorescens was cloned in this
      study. DNA sequencing showed that the open reading frame is comprised of 708
      nucleotides. The coding sequence of the gene is preceded by a potential Shine
      Dalgarno sequence and by a promoter-like structure. Following the stop codon a
      structure reminiscent of the E. coli rho-independent terminator is present. The
      enzyme expressed in an E. coli clone was mostly in the periplasmic space,
      released to the outside of the cell by osmotic shock and purified to homogeneity
      by QAE-Sephadex A-50 and DEAE-Sepharose columns. The native form of the enzyme
      consisted of two identical subunits, each with a molecular weight of 27,000. By
      studying the properties and substrate specificity, the enzyme was classified as
      an arylesterase (EC 3.1.1.2).

PMID- 1368609
TI  - Thermostable S-alkylcysteine alpha, beta-lyase from a thermophile: purification
      and properties.
AB  - S-Alkylcysteine alpha, beta-lyase was found in a thermophile, Bacillus sp. 41A,
      which was newly isolated from soil, and purified to homogeneity from the cell
      extract. The enzyme has a molecular weight of about 76,000, and is composed of
      two subunits identical in molecular weight (39,000). The enzyme requires
      pyridoxal 5'-phosphate as a coenzyme, and catalyzes alpha, beta-elimination of S
      methyl-L-cysteine and its analogs such as S-ethyl-L-cysteine, L-djenkolate, L
      cystine, Se-methyl-L-selenocysteine, and O-methyl-DL-serine. However, S-methyl-D
      cysteine, D-cystine, L-methionine, and L-norleucine were inert. The enzyme also
      catalyzes the beta-replacement reaction of S-methyl-L-cysteine with various
      thiols to yield the corresponding S-substituted cysteines. In addition to S
      methyl-L-cysteine, Se-methyl-L-selenocysteine and O-methyl-DL-serine also serve
      as beta-substituent acceptors in the beta-replacement reaction. The enzyme is
      most active at 70 degrees C and stable at high temperatures. Automated Edman
      degradation provided the N-terminal sequence of the first 44 amino acids. The
      amino acid sequence in the vicinity of the lysyl residue to which pyridoxal 5'
      phosphate is bound, was -Lys-His-Gln-Arg- by Edman degradation of the pyridoxyl
      peptide obtained by digestion with trypsin after reduction with sodium
      borohydride.

PMID- 1368610
TI  - Isolation and partial characterization of three protein-synthesis inhibitory
      proteins from the seeds of Luffa cylindrica.
AB  - Three new proteins which inhibit protein synthesis in rabbit reticulocyte lysates
      were isolated from an extract of sponge gourd (Luffa cylindrica) seeds by
      chromatography on a AF-Blue Toyopearl column followed by FPLC with a Mono S
      column. These three protein-synthesis inhibitory proteins (PSIs) have molecular
      masses of 19 kDa, 15 kDa, and 9 kDa, and were designated 19K-PSI, 15K-PSI, and 9K
      PSI, respectively. Although the 19K-PSI had no effect on protein synthesis in
      HeLa cells, its inhibitory activity on the cell-free protein synthesis was 340-
      and 83-fold stronger than those of ricin A-chain and luffin-a, respectively,
      probably due to hydrolyzing mRNA. The inhibitory activities of 15K- and 9K-PSIs
      on the cell-free protein synthesis were weaker than those of ricin A-chain and
      luffin-a. The 19K-PSI was a glycoprotein having an ordinary amino acid
      composition, three intramolecular disulfide bonds and a blocked N-terminal
      residue, while the 15K-PSI was extraordinarily rich in glycine and the 9K-PSI in
      arginine and glutamic acid (and/or glutamine). The amino acid composition of 19K
      PSI was: Ser27Glx3Gly164Tyr7Lys9His6, and that of 9K-PSI was:
      Asx3Glx25Pro2Gly5Lys2His2Arg25Trp3.

PMID- 1368611
TI  - Production of benzoylformic acid from phenylglycine by Saccharomycopsis
      lipolytica.
AB  - Microbial production of benzoylformic acid (BF), which can be used as a substrate
      of enzymatic synthesis of (R)-(-)-mandelic acid, was investigated. Among 145
      strains of yeasts and actinomycetes, Saccharomycopsis lipolytica (IAM 4964) was
      the best producer of BF from DL-phenylglycine (DL-PG). Culture conditions for BF
      production by the organism were optimized. When 0.2% fructose as a carbon source
      and 0.7% Bacto-tryptone as a nitrogen source were used in the presence of 4% DL
      PG, 14.5 mg/ml of BF was produced (about 37% molar yield) in 4 days of
      cultivation. BF was synthesized from the L-form of PG, but not from the D-form.
      The BF was isolated from culture broth in a crystalline form and
      physicochemically identified.

PMID- 1368612
TI  - Bacillus stearothermophilus glyceraldehyde-3-phosphate dehydrogenase as a source
      of angiotensin-converting enzyme inhibitors.
AB  - The more potent inhibitory activity against angiotensin-converting enzyme (ACE)
      was excised from a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) preparation
      of Bacillus stearothermophilus by heating at 120 degrees C in 1 M AcOH-20 mM HCl,
      as compared with GAPDH preparations of yeast and pig. Sufficient excision of B.
      stearothermophilus ACE inhibitors required a longer proteolysis time of 60 min.
      Two inhibitors were then purified by gel-permeation and reverse-phase
      chromatographies. One of the B. stearothermophilus ACE inhibitors BG-1, was the
      GAPDH peptide 68-77 (Gly-Lys-Glu-Ile-Ile-Val-Lys-Ala-Glu-Arg, IC50: 32 microM).
      Another inhibitor, BG-2 (Gly-Lys-Met-Val-Lys-Val-Val-Ser-Trp-Tyr, IC50: 6
      microM), correspond to GAPDH peptide 304-313. These sequences were quite
      different from those of vertebrate GAPDH peptides and the venom peptide family
      with ACE inhibitory activity. BG-2 was found to be a non-competitive type
      inhibitor, differing from many natural peptide inhibitors. Thus, B.
      stearothermophilus GAPDH seemed to be a good source of new type ACE inhibitors,
      in addition to the advantages due to its thermophilic property.

PMID- 1368613
TI  - Biochemical mechanisms of C-P bond formation of bialaphos: use of gene
      manipulation for the analysis of the C-P bond formation step.
AB  - One of the three C-P bond formation steps, defined as step 5 in the bialaphos
      (BA) biosynthetic pathway, was analyzed using a new BA non-producing mutant NP71.
      The mutant was derived from a BA producer by gene replacement of an unidentified
      region next to the gene responsible for the step 5 deficiency of the mutant
      NP213, obtained by conventional mutation procedures. Biochemical analysis of
      these two mutants indicated that NP71 was defective in the formation of
      carboxyphosphonoenolpyruvate (CPEP), while NP213 lacked the enzyme CPEP
      phosphonomutase, which catalyzed the intramolecular rearrangement of CPEP.

PMID- 1368614
TI  - Improved method for fluorescence labeling of sugar chains with sialic acid
      residues.

PMID- 1368615
TI  - Amino acid compositions and partial sequences of two types of alkaline serine
      proteases from Nocardiopsis dassonvillei subsp. prasina OPC-210.

PMID- 1368617
TI  - Simple procedure for preparing trifluoroacetylprolyl amino acids, acyl components
      in the racemization test for peptide synthesis by GLC.

PMID- 1368616
TI  - Synthesis of plant triosephosphate isomerase in Escherichia coli.

PMID- 1368618
TI  - Synthesis of 4-hydroxy-2-alkenals and 4-oxo-2-alkenols from 4
      tetrahydropyranyloxy-2-butenal and their antimutagenic effect against UV-induced
      Escherichia coli WP2 B/r Trp-.

PMID- 1368619
TI  - Construction of a Bacillus subtilis strain deficient in three proteases.

PMID- 1368620
TI  - Cloning of the glpK gene of Escherichia coli K-12 and its overexpression using a
      'sleeper' bacteriophage vector.

PMID- 1368622
TI  - N-protected tripeptide inhibitors of angiotensin converting enzyme.

PMID- 1368621
TI  - Preparation of glucuronoxylo-oligosaccharides from an acid hydrolysate of corn
      hulls.

PMID- 1368623
TI  - Complete amino acid sequence of luffin-a, a ribosome-inactivating protein from
      the seeds of Luffa cylindrica.

PMID- 1368624
TI  - Utilization and stability of vitamins in serum-containing and serum-free media in
      CHO cell culture.
AB  - The concentrations of four vitamins, ascorbic acid, nicotinamide, choline and
      thiamine were evaluated in the culture supernatant of Chinese hamster ovary (CHO)
      cells. The media used were alpha-modified Eagle's minimum essential medium (MEM
      alpha) supplemented with 10% fetal calf serum, and a 1:1 mixture of Ham's F12 and
      Dulbecco's modified Eagle's medium (DME/F12), containing neither serum nor
      protein. The reference experiment without cells revealed instability of ascorbic
      acid and thiamine. Moreover, a significant amount of each vitamin decreased in
      the culture supernatant. The possibility of growth limitation by vitamin
      depletion is strongly suggested.

PMID- 1368626
TI  - Recombinant yeast-derived hepatitis B vaccine: the prototype for
      biotechnologically derived old vaccines.

PMID- 1368625
TI  - Highly homologous cyclodextrin glycosyltransferases from Bacillus circulans
      strain 8 and a strain of Bacillus licheniformis.

PMID- 1368627
TI  - Structural analysis of repetitive DNA sequences in the goat growth hormone gene
      region.
AB  - Two clones that contain goat growth hormone (gGH) genes were isolated from goat
      genomic library using goat growth hormone cDNA as a probe. One clone CgGH
      contained gGH1 gene, and another clone, EgGH, contained gGH2 and gGH3 genes. The
      clone EgGH contained 491 bp inserted sequence, just upstream of the gGH3 gene,
      which was not present in the clone CgGH. From the sequencing data of the flanking
      regions of these gGH genes, short interspersed repetitive sequences (SINES) were
      found. Four SINES's existed in the CgGH clone and eight SINES's existed in the
      EgGH clone. The number of the repetitive DNA sequences in the goat genome was
      estimated about 10(2) copies from the analysis of the reassociation rate. As the
      number of gGH genes (gGH1, gGH2, and gGH3) per genome was different among
      individual goats, DNA fragments containing gGH1 gene, and that containing gGH2
      and gGH3 genes, were estimated to be allelic on the goat chromosome.

PMID- 1368628
TI  - The synthesis of new xylosyloligosaccharides by transxylosylation with
      Aspergillus niger beta-xylosidase.
AB  - The synthesis of xylosyloligosaccharides from beta-(1----4)-xylobiose in the
      presence of D-mannose by transxylosylation with beta-xylosidase from Aspergillus
      niger IFO 6662 was studied. At first, the transxylosylation products were
      separated by charcoal column chromatography in 5% ethanol elution into three
      peaks, P-1, P-2, and P-3. They were further separated on thin layer
      chromatography, and their three products, saccharides O-4, O-5, and O-N were
      purified by preparative paper chromatography. Saccharides O-4 and O-5 were
      identified as O-beta-D-xylopyranosyl-(1----4)-D- mannopyranose and O-beta-D
      xylopyranosyl-(1----6)-D-mannopyranose, respectively, by measurement of the
      degree of polymerization, specific rotation, acid hydrolysis, and methylation
      analysis. By 1H-NMR spectroscopy in addition to these analyses, saccharide O-N
      was identified as O-beta-D-xylopyranosyl-(1----1')-beta-D-xylopyranose, a new
      nonreducing xylobiose.

PMID- 1368629
TI  - Streptococcal antitumor protein: expression in Escherichia coli cells and
      properties of the recombinant protein.
AB  - Streptococcal antitumor protein (SAGP) was produced by transformed E. coli JM103
      carrying the SAGP gene downstream from the tac promoter. The purified recombinant
      SAGP had the same N-terminal amino acid sequence as that of the native SAGP
      isolated from Streptococcus pyogenes Su cells. Gel filtration analysis showed
      that the recombinant SAGP was a dimer, while the native SAGP was a tetramer. When
      the antitumor activity was tested against sarcoma 180 cells, the IC50 of the
      recombinant SAGP was 0.3 microgram/ml, about a quarter as active as the native
      SAGP. These results suggest that the quaternary structure of SAGP is important
      for the antitumor activity.

PMID- 1368630
TI  - New types of glycolipids from the surface lipids of Nicotiana umbratica.
AB  - The surface lipids of Nicotiana umbratica contained several varieties of
      glycolipids. Three types of glucose esters and five types of sucrose esters were
      isolated and identified from this species. These glycolipids contained short
      chain fatty acids such as acetic, methylpropionic, methylbutyric, 3
      methylpentanoic, 4-methylpentanoic and methylhexanoic acids. The acetylated
      positions of each compound were determined by 2-D NMR, using the HMBC technique.
      The structures of the glucose esters were 1,6-di-O-acetyl-2,3-4-tri-O-acyl-alpha
      D-glucopyranose (I), 6-O-acetyl-2,3,4-tri-O-acyl-alpha-D-glucopyranose (II) and
      2,3,4-tri-O-acyl-alpha, beta-D-glucopyranose (III). The structures of the sucrose
      esters were 6-O-acetyl-2,3,4-tri-O-acyl-alpha-D-glucopyranosyl-1,3-di-O-acetyl
      beta- D- fructofuranoside (IV), 2,3,4-tri-O-acyl-alpha-D-glucopyranosyl-1,3-di-O
      acetyl-beta-D-fructofur anoside (V), 6-O-acetyl-2,4-di-O-acyl-alpha-D
      glucopyranosyl-3-O-acetyl-beta-D- fructofuranoside (VI), 2,3,4-tri-O-acyl-alpha-D
      glucopyranosyl-3-O-acetyl-beta-D-fructofuranosi de 2,3,4-tri-O-acyl-alpha-D
      glucopyranosyl-3-O-acetyl-beta-D-fructofuranosi de (VII) and 2,3,4-tri-O-acyl
      alpha-D-glucopyranosyl-beta-D-fructofuranoside (VIII). Among them, I, IV, V and
      VI were isolated for the first time from plants of the family Solanaceae. These
      newly isolated glycolipids were inhibitory against barnyardgrass growth.

PMID- 1368631
TI  - Inhibition of prolyl endopeptidase by synthetic peptide fragments of human beta
      casein.
AB  - It has been suggested that peptide inhibitors of prolyl endopeptidase (PEP) may
      act as anti-amnestic agents. In the hope of finding PEP inhibitors in milk
      proteins, we synthesized a total of 37 human beta-casein peptide fragments
      containing proline residues. It was found that the peptides with PEP inhibition
      activity in vitro were located in the region of amino acid residues 49-59 of
      human beta-casein. The most potent inhibitor was Ile-Tyr-Pro-Phe-Val-Glu-Pro-Ile
      (IC50 = 8 microM).

PMID- 1368632
TI  - Development of a protein-free medium with ferric citrate substituting transferrin
      for the cultivation of mouse-mouse hybridomas.

PMID- 1368633
TI  - Unique enzymatic properties of alpha-amylase-III from suspension-cultured rice
      cells.

PMID- 1368634
TI  - Synthesis and antimicrobial activity of 2'-deoxypuromycin.
AB  - 2'-Deoxypuromycin (2) was synthesized to learn the effect of the 2'-hydroxyl
      group on the biological activity. Acylated xylose 3 was condensed with silylated
      6-chloropurine to give beta-D-xylofuranosyl-6-chloropurine derivative 4, whose 6
      dimethylamination, 2'-deoxygenation and deprotection afforded 2'-deoxy-beta-D
      xylofuranosyl purine analog 7. The latter was converted to 2'-deoxypuromycin (2)
      in 8 steps. 2'-Deoxy analog 2 showed only weak antimicrobial activity compared
      with that of puromycin (1).

PMID- 1368636
TI  - Solid-phase synthesis and crystallization of [Asn22, Gln25, Asn26]-A-chain
      [Asn49, Glu50]-B-chain-monellin, an analogue of the sweet protein monellin.
AB  - The sweet protein monellin consists of two noncovalently associated polypeptide
      chains, the A chain of 44 amino acid residues and the B chain of 50 residues. The
      [Asn22, Gln25, Asn26]-A chain, an anologue of the A chain, was synthesized by the
      stepwise Fmoc-solid-phase method in an overall yield of 13.4%. The synthetic A
      chain analogue was combined with the [Asn49, Glu50]-B chain, which was left over
      from a previous work, to give [Asn22, Gln25, Asn26]-A-chain-[Asn49,Glu50]-B-chain
      monellin in a yield of 26.2%. This synthetic monellin analogue was approximately
      550 times sweeter than sucrose. Changing the carboxyl groups of Asp22, Glu25, and
      Asp26 of the A chain to amide groups significantly decreased the sweetness
      potency. Crystallization was performed by a vapor diffusion method.

PMID- 1368635
TI  - Expression and secretion of bovine beta-lactoglobulin in Saccharomyces
      cerevisiae.
AB  - A bovine beta-lactoglobulin (beta-LG) was expressed in Saccharomyces cerevisiae
      carrying bovine pre-beta-LG cDNA and secreted into its growth medium. The
      expression plasmid was constructed by inserting the whole coding region of the
      cDNA encoding pre-beta-LG between the promoter and terminator of the yeast
      glyceraldehyde 3-phosphate dehydrogenase gene of pYG100, a yeast expression
      vector. In the supernatant of the yeast growth medium, beta-LG with a native
      conformation was detected by sandwich ELISA, and its amount was estimated to be
      1.1 mg/l. A Western-immunoblotting analysis revealed that beta-LG secrected in
      the growth medium had the same mobility as that of authentic bovine beta-LG. The
      N-terminal sequence was also identical with that of authentic mature bovine beta
      LG.

PMID- 1368637
TI  - Molecular cloning of cDNA encoding a human heat-shock protein whose expression is
      induced by adenovirus type 12 E1A in HeLa cells.
AB  - We have identified by differential plaque hybridization, human cDNA clones
      encoding a member of a heat-shock protein family (hsp 90 alpha) in the cDNA
      library of Adenovirus Type 12 E1A transfected HeLa cells. The complete nucleotide
      sequence of one of the clones (pHB76-114A) was identified. The sequence of 2912
      base pairs had a single reading frame with a coding potential for an 84,672-Da
      protein. The amino acid sequence was highly homologous, but not identical, to
      that of the human hsp 90 alpha gene isolated from human peripheral blood
      lymphocytes [M. Yamazaki, K. Akaogi, T. Miwa, T. Imai, E. Soeda and K. Yokoyama,
      Nucleic Acids Res., 17, 7108 1989)]. This cDNA hybridized with RNA species which
      increased 5- to 20-fold upon heat shock and more than 5-fold in the
      differentiation stage of human Tera 2 cells.

PMID- 1368638
TI  - Action pattern of Streptomyces griseus chitinase on partially N-acetylated
      chitosan.
AB  - Oligosaccharides produced during the course of the hydrolysis of 25% N-acetylated
      chitosan by Streptomyces griseus chitinase were fractionated by CM-Sephadex C-25
      and Toyopearl HW-40F column chromatographies. Sugar compositions and sequences of
      main oligosaccharides were identified by N-acetylation, exo-splitting with beta
      GlcNAcase and beta-GlcNase, and nitrous acid degradation. In addition to N
      acetylated saccharides, GlcNAc, (GlcNAc)2, and (GlcNAc)3, hetero
      chitooligosaccharides such as GlcN.GlcNAc, GlcN.GlcNAc.GlcNAc, GlcN.GlcN.GlcNAc,
      GlcN.GlcNAc.GlcNAc.GlcNAc, GlcNAc.GlcN.GlcNAc.GlcNAc, GlcN.GlcNAc.GlcN.GlcNAc,
      and GlcN.GlcN.GlcNAc.GlcNAc were identified. These results indicate that
      Streptomyces griseus chitinase specifically cleaves the N-acetyl-beta-D
      glucosaminidic linkages in partially N-acetylated chitosan.

PMID- 1368639
TI  - Purification and characterization of an antihypertensive compound from
      Lactobacillus casei.
AB  - Antihypertensive compounds were purified from an extract of autologous
      Lactobacillus casei cell lysates. The most effective compounds were
      polysaccharide-glycopeptide complexes, found in the cell wall. The average
      molecular weight was estimated as 180,000 from gel filtration using Sephacryl S
      300. The polysaccharide moiety of the complexes consisted of glucose, rhamnose,
      and galactose, whereas the glycopeptide moiety consisted of N-acetylglucosamine,
      N-acetylmuramic acid, asparagine, glutamine, alanine, and lysine. The varieties
      of the components of these moieties were constant and independent of complex
      molecular size. When these complexes were orally administered to spontaneously
      hypertensive rats (SHR) and renal hypertensive rats (RHR) at doses of 1 mg/kg
      body weight, systolic blood pressure (SBP) decreased by 10-20 mmHg 6 to 12 hr
      after administration without any change in heart rate. Appreciable hypotensive
      activity was lost by treating the complexes with hydrofluoric acid, which
      hydrolytically cleaves the phosphodiester bond between the polysaccharide and
      glycopeptide moiety.

PMID- 1368640
TI  - Nucleotide sequence of the gene coding for the BanIII DNA methyltransferase in
      Bacillus aneurinolyticus.
AB  - The gene coding for the ATCGAT specific BanIII DNA methyltransferase (M-BanIII)
      of Bacillus aneurinolyticus was cloned and its nucleotides sequenced. The coding
      region was assigned on the nucleotide sequence on the basis of the N-terminal
      amino acid sequence and molecular weight of the enzyme. The M-BanIII gene coded
      for a protein of 580 amino acid residues (MW 66,344). Comparison with other
      methylases indicated that the M-BanIII sequence contained a segment of tetra
      amino acids, NPPY, characteristic of N6-adenine methylases. In addition, some
      homologous regions were found in the sequences of type II adenine methylases
      PaeR7I(CTCGAG), TaqI(TCGA) and PstI(CTGCAG), containing TCGA within the
      recognition sequences.

PMID- 1368641
TI  - Extracellular production of human tumor necrosis factor-alpha by Escherichia coli
      using a chemically-synthesized gene.
AB  - A DNA fragment of approximately 490 base pairs encoding human TNF was chemically
      synthesized and expressed within Escherichia coli cells. Furthermore,
      extracellular production of human TNF and several N-terminal deletion mutants of
      TNF was attempted using the excretion vector pEAP8. The TNF mutant with two N
      terminal amino acids deleted (N delta 2-TNF) was efficiently excreted into the
      culture medium by E. coli carrying the plasmid pEXTNF3. In this clone, the signal
      peptide was correctly processed during the excretion. The E. coli-excreted N
      delta 2-TNF had higher antitumor activity than wild-type TNF or N delta 2-TNF
      produced intracellularly by E. coli.

PMID- 1368642
TI  - Structures of sugar chains of water-soluble glycoproteins in developing castor
      bean cotyledons.
AB  - The structures of sugar chains from the water-soluble glycoproteins in developing
      castor beans have been identified. The structural analyses were done by a
      fluorescence method combined with exoglycosidase digestions and 1H-NMR
      spectroscopy. The identified structures fell into two categories; one was an
      oligomannose-type, the other xylomannose-type or xylose-containing type. Among
      these oligosaccharides, Man3Fuc1Xyl1GlcNAc2 (M3FX; 38%) and Man6GlcNAc2 (M6B;
      22%) were the major structures. The higher mannose-content oligosaccharides (Man8
      7GlcNAc2) were only 4.1%, and the further-modified structures (GNM3FX, M2FX) than
      M3FX were 22% of the total.

PMID- 1368643
TI  - The complete amino acid sequence of antiviral protein from the seeds of pokeweed
      (Phytolacca americana).
AB  - The complete amino acid sequence of antiviral protein from the seeds of pokeweed
      (Phytolacca americana) has been determined. This has been done by the sequence
      analysis of peptides derived by enzymatic digestion with trypsin, pepsin, and
      lysylendopeptidase, as well as by chemical cleavage with cyanogen bromide. The
      protein consists of 261 amino acid residues containing two disulfide bonds and
      has a calculated molecular mass of 29167 Da. The two disulfide bonds connect Cys
      34 to Cys-258 and Cys-84 to Cys-105. Comparison of this sequence with the
      sequence of the ricin A-chain shows that there are identical residues at 76
      positions in the two molecules (30% identity), having an extended region of
      highly conserved sequence at positions 170-183 (IQMXSEAARFXYIE). In contrast, the
      internal regions at positions 77-119 and 141-169 and the C-terminal 15 amino acid
      residues are less homologous in the two proteins.

PMID- 1368644
TI  - Identification of Cd-binding peptides of fission yeast Schizosaccharomyces pombe
      by FRIT-FAB LC/MS.

PMID- 1368645
TI  - Synthesis of peptides consisting of essential amino acids by a reactor system
      using three proteinases and an organic solvent.

PMID- 1368646
TI  - Structure of syringotoxin B, a phytotoxin produced by citrus isolates of
      Pseudomonas syringae pv. syringae.

PMID- 1368647
TI  - Survey of neutral aminopeptidases in bovine, porcine, and chicken skeletal
      muscles.
AB  - A survey of the total aminopeptidase activity of bovine, porcine, and chicken
      skeletal muscles at neutral pH was done, using the beta-naphthylamide derivatives
      of nine amino acids, DEAE-cellulose column chromatography of the muscle extract
      found at least four types of aminopeptidases in porcine and chicken muscles.
      Aminopeptidase B and aminopeptidase C were commonly recognized in bovine,
      porcine, and chickens muscles. Hydrolase H was recognized in porcine and chicken
      muscles. Aminopeptidase nC and hydrolase H had high activity against almost all
      substrates. The substrate specificities of both enzymes were fairly compatible
      with the pattern of free amino acids which increased during the storage of
      bovine, porcine, and chicken meats [Agric. Biol. Chem. 52, 2323 (1988)],
      indicating that aminopeptidase C and hydrolase H are responsible for the
      increment of free amino acids during aging of these muscles.

PMID- 1368648
TI  - New pyrrolobenzodiazepine antibiotics, RK-1441A and B. II. Isolation and
      structure.
AB  - Antibacteriophage antibiotics, RK-1441A and B, related to neothramycin were
      isolated from the culture broth of Streptomyces sp. and their structures were
      deduced from spectroscopic analyses. The structure of RK-1441A was 8,11-dihydroxy
      3,7-dimethoxy-5-oxo-1H-pyrrolo[2,1-c:1,4]benzodiazepine. RK-1441B is a tautomeric
      mixture at C-3 of the structure, 3,8,11-trihydroxy-7-methoxy-5-oxo-1H-pyrrolo[2,1
      c:1,4]benzodiazepine.

PMID- 1368649
TI  - Stereoselective total synthesis of wheat flour ceramide dihexoside.
AB  - A plant glycosphingolipid, O-(beta-D-mannopyranosyl)-(1----4)-O-(beta-D
      glucopyranosyl)-(1----1)-(2 S,3S,4R)-4-hydroxy-N-tetracosanoylsphinganine 1, and
      the stereoisomer, O-(alpha-D-mannopyranosyl)-(1----4)-O-(beta-d-glucopyranosyl)
      (1----1)-( 2S,3S,4R)-4-hydroxy-N-tetracosanoylsphinganine 6, were synthesized in
      a stereo- and regio-controlled way.

PMID- 1368650
TI  - Toxicity of dimethyl sulfoxide as a solvent in bioassay system with HeLa cells
      evaluated colorimetrically with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide.
AB  - The toxicity of dimethyl sulfoxide (Me2SO) was examined in HeLa cells cultured at
      37 degrees C for up to 72 hr. The growth of the cells was measured by a
      colorimetric method with the use of 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT), which gave good correlation between the cell
      number and the color development from the reduction of MTT under suitable
      conditions. When the initial number of cells was 3 x 10(4)/ml, Me2SO at 1% or
      less had no apparent effect on proliferation for up to 48 hr of incubation, but
      in longer incubations, cell growth was repressed. When the initial number of
      cells was 3 x 10(5)/ml, the effect of Me2SO was similar.

PMID- 1368651
TI  - Complete amino acid sequence of luffin-a, a ribosome-inactivating protein from
      the seeds of sponge gourd (Luffa cylindrica).
AB  - The complete amino acid sequence of luffin-a has been determined. Twenty-two
      peptides were isolated from the tryptic digest of luffin-a and sequenced
      employing the DABITC/PITC double coupling method. Overlaping of these peptides
      was achieved by analyzing the chymotryptic peptides or CNBr-fragments of luffin-a
      and their S. aureus V8 protease peptides. Luffin-a consists of 248 amino acid
      residues and its relative molecular mass is calculated to be 27,021 Da, excluding
      the attached sugar chains reasoned to be present at each Asn residue of positions
      28, 33, 77, 84, 206, and 227. A comparison with the sequence of ricin A-chain
      showed 33% sequence identity indicating that these proteins are homologous.

PMID- 1368652
TI  - Staurosporine, a prolyl endopeptidase inhibitor.

PMID- 1368653
TI  - Activity of poly(gamma-glutamylcysteinyl)glycine synthesis in crude extract of
      fission yeast, Schizosaccharomyces pombe.

PMID- 1368654
TI  - Enzyme immobilization on glycosylated edible proteins.

PMID- 1368655
TI  - Positions of substituted amino acids in soybean beta-amylase isoenzymes.

PMID- 1368656
TI  - Molecular cloning and partial amino acid sequence of rice ferredoxin-nitrite
      reductase.

PMID- 1368657
TI  - Promotive and inhibitory effects of raw starch adsorbable fragments from
      pancreatic alpha-amylase on enzymatic digestions of raw starch.
AB  - The enzymatically inactive but raw-starch-adsorbable peptide fragments designated
      as Gp-pan P and Gp-pan I were obtained from a tryptic digest of heat-inactivated
      hog pancreatic alpha-amylase. These two glycopeptide fragments were purified with
      Sephadex G-75, DEAE-Sephadex A-50, and HPLC and were found to be homogeneous on
      disc gel electrophoresis. Gp-pan P and I had molecular weights of 20,000 and
      30,000 with SDS-PAGE, carbohydrate contents of 10% and 7%, N-terminal amino acids
      Gly-Trp and Ala-Val, and C-terminal amino acids Gly-Arg and Ile-Lys. Gp-pan P had
      promotive but Gp-pan I inhibitory effects on raw starch digestion by Aspergillus
      awamori var. kawachi glucoamylase I and Bacillus subtilis 65 alpha-amylase.

PMID- 1368658
TI  - Purification and characterization of superoxide dismutase from Aerobacter
      aerogenes.
AB  - Superoxide dismutase (SOD) was purified from Aerobacter aerogenes IFO 3317 to an
      electrophoretically homogeneous state and partially characterized. SOD was
      purified by ammonium sulfate fractionation, column chromatography on DEAE
      Sephadex A-50, gel filtration on Sephadex G-100, phenyl-Toyopearl 650 M
      hydrophobic chromatography, and hydroxyapatite adsorption chromatography. The
      molecular weight and subunit molecular weight of the purified enzyme were
      estimated to be 45,000 and 22,000, respectively. The isoelectric point of the
      enzyme was about pH 4.0. The purified enzyme remained stable at pH 7.0-11.0, 25
      degrees C for 36 hrs, but was rapidly inactivated below pH 7.0. SOD was stable up
      to 35 degrees C at pH 7.0, but was inactivated at temperatures above that. The
      absorption maximum in the visible range was found at 360 nm, and the enzyme was
      insensitive to cyanide and fluoride, and sensitive to hydrogen peroxide and
      azide. These results suggest that the enzyme is an iron-containing SOD. The amino
      acid composition and the N-terminal sequence of the first 15 amino acids of the
      enzyme exhibited close homology with the other iron-containing SODs.

PMID- 1368659
TI  - Relationship between the limited proteolysis of glycinin and its conformation.
AB  - The relationship between the limited proteolysis and conformation of native
      glycinin was studied by the following methods: analyses of the proteolytic
      digestion of chemically modified glycinin, circular dichroism (CD) measurements,
      a secondary structure prediction from the amino acid sequence and a hydropathy
      index analysis. The locations of tryptic fragments of glycinin were confirmed
      from the N-terminal amino acid sequences of the fragments. T fragments and P
      fragments were located at the N-terminal and central area of the acidic
      polypeptide chains, respectively. One of the cleavage sites was the Arg residue
      of around the 100th from the N-terminal side. The regions digested by limited
      trypsinolysis were presumed to be flexible, hydrophilic and near the surface of
      the molecule by prediction methods from the amino acid sequence. The other
      regions were predicted to be compact and beta-sheet in nature, almost 40-50% of
      the amino acid residues being predicted as beta-sheet from the amino acid
      sequence and from CD data.

PMID- 1368661
TI  - Primary characterization of curved DNA segments cloned from Streptomyces DNA with
      extremely high G/C-contents.
AB  - Until recently, it was assumed that any short DNA segment could be regarded as a
      straight rod. Many instances, however, have been reported in which the helical
      axis was curved. In this study, to gain a general insight into the structural
      features of sequence-directed DNA curvatures, we constructed a set of plasmids
      carrying curved DNA segments, which were randomly cloned from Streptomyces total
      DNA with extremely high G/C-contents. The results of primary characterization of
      these curved DNA segments are presented. Although the cloned DNA segments had
      high G/C-contents, in all cases, several homopolymeric [dA] and [dT] stretches
      were found to be clustered around the centres of the determined nucleotide
      sequences. Furthermore, the clustered [dA] and [dT] stretches were located nearly
      in phase with the DNA helical screw. One of the DNA segments characterized in
      this study appeared to be derived from the giant linear plasmid, SCP1, and
      another from the circular fertility plasmid, SCP2.

PMID- 1368660
TI  - Establishment and characterization of monoclonal antibodies against bovine
      ephemeral fever virus.
AB  - We established fourteen monoclonal antibodies (MAbs) reactive to bovine ephemeral
      fever virus YHL strain, and characterized six representatives including three
      IgG1s (YG3/4, YG5/8, and YG6/7) and three IgMs (YM4/9, YM2/6, and YM6/8). Among
      them, YG3/4 and YM4/9 gave especially strong reactivities to the virus. YM4/9
      reacted specifically with a 43K antigen of the virus, corresponding to the matrix
      protein 1. The other MAbs reacted most strongly with the 43K antigen, but also
      reacted with unknown 23K and 21K antigens. By a simultaneous two-site method
      using YM4/9 and YG3/4, it was possible to detect 10(4.10)TCID50/ml of the virus,
      in the presence of serum.

PMID- 1368662
TI  - Enzymatic formation of 4G-alpha-D-glucopyranosyl-rutin.

PMID- 1368663
TI  - Analysis by deletion and site-directed mutagenesis of promoters of the cell wall
      protein gene operon in Bacillus brevis 47.
AB  - The cell wall protein gene operon of Bacillus brevis 47 has multiple and tandem
      promoters. The precise locations of the two major promoters (P2 and P3) of the
      operon were determined by deletion analysis. This together with results of
      oligonucleotide-directed mutagenesis of the promoter regions confirmed that the 
      35 and -10 sequences of the two promoters proposed previously are essential for
      their promoter activity. A G + C-rich sequence upstream of the -35 region of P2
      and an A-rich sequence upstream of the -35 region of P3 facilitate the
      transcription from P2 and P3, respectively.

PMID- 1368664
TI  - The nucleotide sequences of Bacillus stearothermophilus ribosomal protein S12 and
      S7 genes: comparison with the str operon of Escherichia coli.
AB  - The primary structure of the ribosomal protein S7 from Bacillus
      stearothermophilus (BstS7) was analyzed by a combination of amino acid and DNA
      sequence analysis. Peptide sequence information was derived from tryptic peptides
      of BstS7 by manual Edman degradation. The nucleotide sequence of the 1.5-kb SalI
      fragment from B. stearothermophilus genome, cloned by the Escherichia coli S12
      gene (rpsL) as a hybridization probe, was determined. Comparison of deduced amino
      acid sequence with the corresponding sequences of E. coli ribosomal proteins
      showed that this fragment contains the genes encoding S12, S7, and the N-terminus
      of the elongation factor G. Thus, the organization of this gene cluster is same
      as that in the str operon of E. coli. The amino acid sequence of B.
      stearothermophilus S12 (BstS12) deduced from the nucleotide sequence information
      agrees with the published amino acid sequence of BstS12 [M. Kimura and J. Kimura,
      FEBS Lett., 210, 91 (1987)]. The deduced sequence of B. stearothermophilus S7
      (BstS7), together with sequence information of tryptic peptides, showed that
      protein S7 consists of 155 amino acid residues with a calculated molecular weight
      of 17933 and has 56% amino acid identity with the E. coli S7 (EcoS7).

PMID- 1368665
TI  - Xylose (glucose) isomerase gene from the thermophile Clostridium
      thermohydrosulfuricum; cloning, sequencing, and expression in Escherichia coli.
AB  - The xylose isomerase gene from the thermophile Clostridium thermohydrosulfuricum
      has been cloned, using a fragment of the Bacillus subtilis gene as a probe. The
      complete nucleotide sequence of the gene was analyzed. C. thermohydrosulfuricum
      is the most thermophilic organism from which a xylose isomerase gene has been
      cloned and characterized. Comparison with amino acid sequences from other xylose
      isomerases showed that amino acids involved in substrate binding and
      isomerization are well conserved. Purification of the enzyme produced in E. coli
      was done by heating a cell-free extract at 85 degrees C for 10 min, giving a 20
      fold purified enzyme. The native enzyme is a homomeric tetramer with a molecular
      weight of 200,000.

PMID- 1368666
TI  - Complete amino acid sequence of luffin-b, a ribosome-inactivating protein from
      sponge gourd (Luffa cylindrica) seeds.
AB  - The complete amino acid sequence of luffin-b has been determined. All the twenty
      seven tryptic peptides were isolated by reverse-phase HPLC from the tryptic
      digests of intact luffin-b and one of its CNBr fragments (CB4), and sequenced
      using the DABITC/PITC double coupling method. The overlap of these peptides was
      achieved by analyzing the CNBr fragments and their chymotryptic peptides. Luffin
      b consists of 250 amino acid residues with a relative molecular mass of 27,275
      Da. Investigation for glycosylation sites indicated that Asn at positions 2, 78,
      and 85 might carry sugars. Sequence comparison with luffin-a showed that amino
      acid substitution occurred in 55 positions. Luffin-b contains three glycosylation
      sites instead of the six sites in luffin-a, of which two were found to be
      conserved.

PMID- 1368667
TI  - Multinucleation of macrophages with dextran sulfate in vitro.

PMID- 1368668
TI  - The properties of a tumor necrosis factor mutant with the deletion of alanine-14.

PMID- 1368669
TI  - Characterization of restriction endonuclease BdiSI, an isoschizomer of SfeI, from
      Bacteroides distasonis strain S-7.

PMID- 1368670
TI  - Purification and characterization of a subtilisin inhibitor from seeds of foxtail
      millet, Setaria italica.

PMID- 1368671
TI  - Molecular cloning of mouse peptidylarginine deiminase, and its possible isozyme
      cDNAs.

PMID- 1368672
TI  - Purification and some properties of soybean saponin hydrolase from Aspergillus
      oryzae KO-2.
AB  - We had investigated the enzymatic hydrolysis of soybean saponins and selected
      soybean saponin hydrolase from Aspergillus oryzae KO-2. We attempted purification
      of this enzyme for further characterization. This enzyme was purified 1500-fold
      using ammonium sulfate fractionation and Sephadex G-200 gel filtrations. The
      enzyme was electrophoretically homogeneous and a glycoprotein by PAS staining. By
      gel filtration, the molecular weight of enzyme was 158,000 and SDS-PAGE showed
      the enzyme to have a tetrameric structure composed of heterogeneous subunits of
      35,000 and 45,000. The enzyme activity was stable at temperatures below 40
      degrees C and stable from pH 5.0 to 8.0. The optimum pH was pH 4.5 to 5.0 and the
      optimum temperature was 50 degrees C. The Km and Vmax for soyasaponin I were 0.48
      mM and 9.8 mumol/hr mg protein, respectively. After hydrolysis with the enzyme,
      soyasapogenol B and alpha-L-rhamnopyranosyl (1----2)-beta-D-galactopyranosyl (1--
      -2)-D-glucuronopyranoside were released from soyasaponin I.

PMID- 1368673
TI  - Structure activity relationship of inhibitors specific for prolyl endopeptidase.
AB  - Structural requirements of N-blocked L-proline derivatives as specific inhibitors
      for prolyl endopeptidase were investigated using a series of substrate analogs.
      Replacement of L-proline by its D-isomer remarkably reduced the inhibition.
      Introduction of a sulfur atom in proline and/or in the penultimate pyrrolidine
      rings significantly increased the inhibition, but the introduction of oxygen
      rather diminished the activity. A peptide linkage (acid-amide bond) between the
      proline and the pyrrolidine ring was also required to keep the inhibitory
      activity. A benzyloxycarbonyl group was most effective as an N-blocked component
      of the inhibitors.

PMID- 1368674
TI  - Isolation and sequencing of a gene, C-ADE1, and its use for a host-vector system
      in Candida maltosa with two genetic markers.
AB  - The host-vector systems of an n-alkane-assimilating-yeast, Candida maltosa, that
      we previously constructed consisted of a vector replicating with an ARS region of
      this yeast, and C. maltosa strains J288 (leu2) or CH1 (his5) as hosts. Since each
      of these hosts has a single genetic marker, we have developed a new host-vector
      system using two genetic markers. By UV irradiation of strain CH1, an adenine
      auxotrophic mutant, CHA1, forming red colonies was isolated. A DNA fragment
      complementing this deficiency was isolated from the C. maltosa genome. Since the
      DNA fragment also complemented the ade1 mutation of S. cerevisiae, we termed a
      gene contained in this DNA fragment C-ADE1. The nucleotides of C-ADE1 were
      sequenced. The deduced amino acid sequence (291 residues) had 65.6% homology with
      that of ADE1 of S. cerevisiae (306 residues). Having the cloned C-ADE1 DNA, we
      improved the host-vector system of C. maltosa.

PMID- 1368675
TI  - Prothoracicotropic hormone of the silkworm, Bombyx mori: amino acid sequence and
      dimeric structure.
AB  - Prothoracicotropic hormone (PTTH) of the silkworm, Bombyx mori, was purified and
      its primary structure determined for the most part. From sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of the purified PTTH under non-reducing and
      reducing conditions, and the amino acid sequence and composition analyses of the
      carboxamidomethylated PTTH, we concluded that Bombyx PTTH has a dimeric structure
      consisting of two identical, or nearly identical subunits, held together by
      disulfide bond(s). There exist subunit variants that differ by deletion of only a
      few amino acid residues at the N-terminus, and possibly at the C-terminus also,
      giving rise to a high heterogeneity in the PTTH molecule. The amino acid sequence
      up to the 104th residue from the N-terminus of the longest subunit, except for
      the 41st residue, was determined by sequence analysis of fragment peptides
      produced by lysyl endopeptidase, chymotrypsin and V8 protease digestions, leaving
      only a short C-terminal sequence undetermined. Bombyx PTTH is expected to contain
      a carbohydrate chain bound to an asparagine at position 41, deduced from the cDNA
      sequence.

PMID- 1368676
TI  - Purification and characterization of a base non-specific and adenylic acid
      preferring ribonuclease from the fruit bodies of Lentinus edodes.

PMID- 1368677
TI  - Multiplication of bovine viruses in hamster lung HmLu-1 cells cultured in protein
      free medium.

PMID- 1368678
TI  - Composition and structure of "group B saponin" in soybean seed.
AB  - The composition of "group B saponin" in soybean seed was analyzed by HPLC, and
      six kinds of "group B saponin," named Ba, Bb, Bb', Bc, Bd and Be according to
      elution order from HPLC, were detected. Of these saponins, Ba, Bb, Bb' and Bc
      were identified with soyasaponin V, I, III and II, respectively. Bd and Be were
      novel saponins possessing soyasapogenol E as the aglycone and the same sugar
      chain as Ba and Bb, respectively. These saponins were very unstable in the
      isolated state and had a tendency to form Ba and Bb, respectively. From these
      results, Bd and Be are presumed to be the precursors of Ba and Bb in soybean
      seed.

PMID- 1368679
TI  - Cloning and characterization of the pectate lyase III gene of Erwinia carotovora
      Er.
AB  - A pectate lyase gene III (pel III) of Erwinia carotovora Er was cloned. The gene
      was expressed independently of a vector promoter in both E. carotovora Er and
      Escherichia coli. The pel III product was largely excreted in the culture medium
      of E. carotovora Er, while the product was only exported to the periplasmic space
      and was not excreted in the medium of E. coli. Nucleotide sequence analysis of
      pel III disclosed an open reading frame of 1,122 bp encoding a protein of 374
      amino acids. The deduced amino acid sequence contained the N-terminal 30 amino
      acid sequence from the purified pectate lyase III (PL III) indicating the
      presence of a 22-amino-acid signal peptide. A putative ribosome-binding site was
      found to be 9 bp upstream of the start codon. The location of pel III was about
      5.6 kb downstream of pel I. The PL III showed 80% homology in the amino acid
      sequence with the PL I of E. carotovora Er.

PMID- 1368680
TI  - The glucoamylase cDNA from Aspergillus oryzae: its cloning, nucleotide sequence,
      and expression in Saccharomyces cerevisiae.
AB  - A cDNA for Aspergillus oryzae glucoamylase was cloned, using
      oligodeoxyribonucleotide probes derived from amino sequences of peptide fragments
      of the enzyme. The glucoamylase cDNA, when introduced into Saccharomyces
      cerevisiae, directed the secretion of active glucoamylase into the culture
      medium. The complete nucleotide sequence of the cDNA contained an open reading
      frame encoding 612 amino acid residues. Comparative studies with other fungal
      glucoamylases showed homologies of 67% with A. niger and 30% with Rhizopus oryzae
      of the deduced amino acid sequences. In the five conserved regions reported in
      other fungal glucoamylases, the levels of homologies between those regions of A.
      oryzae and A. niger enzymes were much higher (78-94%). A. oryzae glucoamylase
      contained no peptide region abundant in threonine and serine residue (TS-region),
      like that proposed to adsorb onto raw starch in A. awamori var. kawachii
      glucoamylase.

PMID- 1368681
TI  - Purification and characterization of tissue plasminogen activator secreted by
      human embryonic lung diploid fibroblasts, IMR-90 cells.
AB  - The anti-urokinase-IgG-resistant plasminogen activator secreted by human
      embryonic lung diploid fibroblasts, IMR-90 cells (ATCC, CCL186) was purified to
      homogeneity from serum-free conditioned medium by a four-step procedure. The
      fibroblast plasminogen activator was identified as tissue plasminogen activator
      (t-PA) by the N-terminal sequence of the purified material and the complete amino
      acid sequence deduced from its complementary DNA (cDNA). The apparent molecular
      weight was the range of 64,000 to 68,000 by SDS-PAGE and was in the range of
      69,000 to 72,000 by gel filtration. The fibroblast t-PA showed a stricter
      substrate specificity than urokinase in enzymatic hydrolysis of various
      chromogenic substrates. Compared to urokinase, the fibrobrast t-PA was more
      stable by heating at 95 degrees C for five min and was stable from pH 5 to 10.
      The fibrorast t-PA had a higher affinity for fibrin than urokinase.

PMID- 1368682
TI  - Cloning and expression of cDNA coding for the major house dust mite allergen Der
      f II in Escherichia coli.
AB  - A cDNA library corresponding to mite protein was screened using anti-Der f II, a
      major allergen from the house dust mite Dermatophagoides farinae, antibody. Three
      possible clones were obtained that contained cDNA fragments coding for Der f II,
      and the nucleotide sequences of the fragments were determined. There were minor
      differences observed affecting the deduced amino acid sequence among the three
      cDNA fragments. The amino acid sequence of the purified native Der f II protein
      could be analyzed to 45 residues from the N-terminus. As a result of comparison,
      all the three cDNA fragments code for a mature protein with a derived molecular
      weight of about 14,000. The amino acid sequence was not homologous to any known
      protein sequences and it contained six cysteine residues and no N-glycosylation
      sites.

PMID- 1368683
TI  - Cloning and expression of the sarcosine oxidase gene from Bacillus sp. NS-129 in
      Escherichia coli.
AB  - The gene coding for a thermostable sarcosine oxidase (EC 1.5.3.1) was isolated
      from Bacillus sp. NS-129. The primary structure of sarcosine oxidase deduced from
      the nucleotide sequence was a protein composed of 387 amino acids with molecular
      weight 42,955. When the sarcosine oxidase was overproduced to about 35% of
      soluble protein in E. coli under the control of a lac promoter, the sarcosine
      oxidase activity of the crude extract was increased 3-fold by the addition of
      FAD. This indicates that most of the enzyme is accumulated in an active form, a
      flavinless aporotein, in the cell.

PMID- 1368684
TI  - Structures and activity of angiotensin-converting enzyme inhibitors in an alpha
      zein hydrolysate.
AB  - Peptides that inhibit angiotensin-converting enzyme (ACE) were isolated from
      alpha-zein hydrolysate prepared with thermolysin. Their chemical structures were
      identified by Edman degradation and fast-atom bombardment mass spectrometry. Most
      of them were found to be tripeptides such as Leu-Arg-Pro, Leu-Ser-Pro, and Leu
      Gln-Pro, having IC50 values of 0.27, 1.7, and 1.9 microM, respectively. These
      peptides were synthesized by a solid phase procedure and had similar ACE
      inhibitory activities as the isolated inhibitors. The hypotensive activity of Leu
      Arg-Pro on spontaneously hypertensive rats was also investigated, with the result
      that the the blood pressure decreased by 15 mmHg after a 30 mg/kg intravenous
      injection.

PMID- 1368685
TI  - N-acetyl-D-glucosamine-asparagine structure in ribosome-inactivating proteins
      from the seeds of Luffa cylindrica and Phytolacca americana.
AB  - Glycosylation-site-containing peptides were isolated from the proteolytic digests
      of luffin-a, luffin-b, PAP-S and CNBr-fragments of PAP-S by reverse-phase HPLC,
      and their amino acid compositions and sequences were analyzed. Six peptides were
      obtained from luffin-a, and three each from luffin-b and PAP-S. All of these
      peptides were negative toward the phenol-H2SO4 reaction and gave only N-acetyl-D
      glucosamine in gas chromatography after methanolysis and reacetylation. Amounts
      of N-acetyl-D-glucosamine in these peptides were determined as D-glucosamine to
      be approximately one mol per peptide by an amino acid analyzer after HCl
      hydrolysis. Based on these results we concluded that Asn residues at positions of
      28, 33, 77, 84, 206, and 227 in luffin-a, of 2, 78, and 85 in luffin-b, and of
      10, 44, and 255 in PAP-S were glycosylated with only GlcNAc, and contained one
      residue per site.

PMID- 1368687
TI  - Galactomannan and isolichenan components of the carbohydrate-rich lichen Ramalina
      ecklonii (Spreng.) Mey. & Flot.

PMID- 1368686
TI  - Cloning, sequencing, and characterization of the intracellular invertase gene
      from Zymomonas mobilis.
AB  - The structural gene for the intracellular invertase E1 of Zymomonas mobilis
      strain Z6C was cloned in a 2.25-kb DNA fragment on pUSH11, and expressed in
      Escherichia coli HB101. The enzyme produced by the E. coli carrying pUSH11 was
      purified about 1,122 fold to homogenicity with a yield of 4%. The molecular
      weight and substrate specificity of the enzyme were identical with those of the
      intracellular invertase E1 from Z. mobilis. The nucleotides of the cloned DNA
      were sequenced; they included an open reading frame of 1,536 bp, coding for a
      protein with a molecular weight of 58,728. The N-terminal amino acid sequence
      predicted was identical with the sequence of the first 20 N-terminal amino acid
      residues of the protein obtained by Edman degradation. Comparison of the
      predicted amino acid sequence of E1 protein with those of the four other known
      beta-D-fructofuranosidases from Escherichia coli, Bacillus subtilis, and
      Saccharomyces cerevisiae indicated a stronger homology in the N-terminal portion
      than in the C-terminal portion.

PMID- 1368688
TI  - Cloning of a lignostilbene-alpha,beta-dioxygenase gene from Pseudomonas
      paucimobilis TMY1009.

PMID- 1368689
TI  - Purification and some properties of protease I having transfer action from
      Streptomyces griseus var. alcalophilus.
AB  - Streptomyces griseus var. alcalophilus was selected because it secreted a unique
      protease (protease I) that catalyzed the transfer reaction forming the hydroxamic
      acids of various amino acids. Protease I was purified to the electrophoretically
      homogeneous state and an activity of more than 125-fold that of the culture
      broth. The molecular weight of the enzyme was estimated to be 25,000 by gel
      filtration. The enzyme was most active in neutral pH for the transfer reaction
      forming phenylalanine hydroxamic acid, although for the hydrolytic reaction with
      casein as substrate it was most active in alkaline pH. The enzyme was inhibited
      by diisopropylfluorophosphate. Protease I catalyzed the transfer reaction
      synthesizing the hydroxamic acids of hydrophobic, acidic, basic, and small
      aliphatic amino acids such as Phe, Tyr, Leu, Asp, Glu, Arg, Lys, Ala, and Gly.
      These results indicate that protease I has broad donor specificity. It is also
      considered that protease I is a unique enzyme with transfer activity, and
      distinct from the alkalophilic proteinase reported previously [Yamamoto et al.,
      Agric. Biol. Chem., 38, 37 (1974)].

PMID- 1368690
TI  - Nucleotide sequence of celC307 encoding endoglucanase C307 of Clostridium sp.
      strain F1.
AB  - The celC gene, encoding endoglucanase C, of Clostridium thermocellum was recently
      sequenced while a promoter region was not identified. In this study, the
      nucleotide sequence of celC307 of Clostridium sp. strain F1 was identified and
      compared with that of the C. thermocellum gene. The open reading frame was
      composed of 1029 nucleotides and the deduced amino acid sequence corresponded to
      a protein of a molecular weight of 40,905. We identified promoter sequences
      (TGGACA and TATAAT) at a position about 150 nucleotides upstream of the
      initiation codon. Six substitutions were found in the coding region, 3 leading to
      amino acid replacements. Five substitutions and 1 deletion of a nucleotide were
      found in the region upstream of the initiation codon, 1 present at the promoter
      sequence. Overproduction of endoglucanase C307 (EGC307) in Escherichia coli
      strongly inhibited the cell growth of the host strain. Around 50% of EGC307
      produced in E. coli was detected in the periplasmic fraction. The N-terminal
      amino acid sequence suggested that this protein was exported into the periplasm
      without processing of a signal peptide.

PMID- 1368691
TI  - Production and localization of enzymes on soft gel cultivation.
AB  - Production and localization of glutaminase and leucine aminopeptidase (LAP) in
      soft gel cultivation were compared with those in koji and liquid cultivations.
      The enzymes were detected only in the whole-mycelial-mat fraction by soft gel
      cultivation, but in both intracellular and extracellular fractions by the other
      two methods. The enzyme species of glutaminase and LAP in soft gel cultivation
      were analyzed by ion exchange and gel filtration column chromatographies. Three
      species of glutaminase and four (or five) species of LAP were formed in the whole
      mycelial-mat fraction. The intracellular and extracellular fractions of the koji
      and liquid cultivations contained different species of enzymes.

PMID- 1368692
TI  - Purification and primary structure of C-1027-AG, a selective antagonist of
      antitumor antibiotic C-1027, from Streptomyces globisporus.
AB  - C-1027-AG, a selective antagonist of antitumor antibiotic C-1027, was isolated by
      column chromatography on DEAE-cellulose, butyl-Toyopearl and Sephadex G-50 from a
      culture filtrate of Streptomyces globisporus. The amino acid sequence of purified
      C-1027-AG was determined with a protein sequencer on the basis of fragment
      peptides obtained by enzymatic hydrolysis with lysylendopeptidase, V8 protease,
      endopeptidase AspN and chymotrypsin, after performic acid oxidation. C-1027-AG is
      shown to consist of a single polypeptide chain cross-linked by two disulfide
      bonds, and to contain a total of 110 amino acid residues with alanine and glycine
      as its amino- and carboxyl-termini, respectively; its molecular weight was
      calculated to be 10,500 daltons. The primary structure of C-1027-AG is indicated
      to be identical to the protein moiety of C-1027, and is highly homologous to the
      sequences of antitumor proteins obtained from other Streptomyces species.

PMID- 1368693
TI  - Purification, characterization, and amino acid sequence of foxtail millet trypsin
      inhibitor III.
AB  - One of the major trypsin inhibitors of foxtail millet, Setaria italica, was
      purified from a seed extract to an electrophoretically homogeneous protein by
      methods including chromatofocusing and affinity chromatography. This inhibitor
      (FMTI-III) was shown to be specific and single-headed for trypsin. The molecular
      weight and the amino acid composition together with the above nature were
      identical with those of another major trypsin inhibitor (FMTI-II) previously
      purified from foxtail millet grain. Sequence analysis of FMTI-III indicated that
      the protein contains 67 amino acid residues, the sequence of which is the same as
      that of FMTI-II except for the replacement of the C-terminal glutamine by
      glutamic acid. This single amino acid substitution had no effect on inhibitor
      enzyme association.

PMID- 1368694
TI  - Characterization and structure of the cellulase gene of Bacillus subtilis BSE616.
AB  - The Bacillus subtilis carboxymethyl cellulase (CMCase) gene originally cloned on
      a 3.2-kb PstI DNA fragment has been localized in a 1.5-kb Sau3AI fragment by a
      series of subclonings into plasmid pUC19. During the process the promoter region
      and Shine-Dalgarno (SD) sequence were deleted, but the 1.5-kb insert was shown to
      direct the synthesis of CMCase in scherichia coli to a high level, probably with
      the aid of lac promoter. We analyzed the complete nucleotide sequence of the
      CMCase gene. The CMCase gene is 1500-bp long, encoding a polypeptide of 499 amino
      acids and a stop codon. The putative "-35" region (TAGACA), "-10" region
      (TACAAT), and ribosome binding site (RBS) (AAGGAGG) have also been identified in
      the 5' flanking region. Comparison of the nucleotide sequence to three other
      published endo-beta-1,4-glucanase genes of B. subtilis strains shows that these
      sequences share very strong homology. It seems that the cellulase genes have been
      derived from a common ancestor by spontaneous mutation. The probability of
      carboxy-terminal processing of the CMCase protein is also discussed.

PMID- 1368695
TI  - Further study on the 1,4-alpha-transglucosylation of rubusoside, a sweet steviol
      bisglucoside from Rubus suavissimus.
AB  - Rubusoside (the beta-D-glucosyl ester of 13-O-beta-D-glucosyl-steviol), which is
      the major sweet principle of leaves of Rubus suavissimus S. Lee, was subjected to
      1,4-alpha-transglucosylation by the cyclodextringlucanotransferase-starch system
      (the CGTase system). The tri- and tetra-glucosylated products were isolated
      together with the mono- and di-glucosylated products, which had already been
      isolated. A prominent increase in intensity of the sweetness was observed for the
      compounds which were di- and tri-glucosylated at the 13-O-glucosyl moiety. This
      result further substantiated the structure-sweetness relationship for 1,4-alpha
      glucosylated compounds of steviol-glycosides reported previously. For protection
      of the 19-COO-glucosyl moiety against glucosylation by the CGTase system, the 4
      hydroxyl group of the 19-COO-glucosyl moiety was beta-galactosylated by the beta
      galactosidase-lactose system. This galactosylated compound was subjected to a
      regio-selective glucosylation of the 13-O-glucosyl moiety by the CGTase system,
      which was followed by enzymic elimination of the galactosyl group to furnish an
      exclusive preparation of the improved sweeteners just mentioned.

PMID- 1368696
TI  - Cloning and nucleotide sequences of the complementary and genomic DNAs for the
      alkaline protease from Acremonium chrysogenum.
AB  - Complementary DNA encoding Ac. chrysogenum alkaline protease (Alp) was isolated
      from the Ac. chrysogenum ATCC11550 cDNA library by express-blot assay. The
      genomic DNAs encoding Ac. chrysogenum Alp were isolated from the Ac. chrysogenum
      genomic DNA library using the cloned cDNA as a probe. The 3150 nucleotides of the
      gene were sequenced. The prepro-Alp consists of 402 amino acids and two
      intervening sequences are found within the coding region. The amino acid sequence
      of Ac. chrysogenum Alp has 57% homology to that of Aspergillus oryzae Alp. The
      entire cDNA, encoding Ac. chrysogenum Alp, when introducing into the yeast
      Saccharomyces cerevisiae, directed the secretion of enzymatically active Alp into
      the culture medium.

PMID- 1368697
TI  - Purification and properties of purine nucleoside phosphorylase from
      Brevibacterium acetylicum ATCC 954.
AB  - Purine nucleoside phosphorylase of Brevibacterium acetylicum ATCC 954, which
      catalyzes the production of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3
      carboxamide), a potent antiviral agent, from purine nucleoside and 1,2,4-triazole
      3-carboxamide in a high yield, was purified 49-fold. This enzyme had a molecular
      weight of 31,000 and was a monomer. The isoelectric point of the enzyme was 4.7.
      The optimal temperature and pH of inosine phosphorolyzing reaction catalyzed by
      the enzyme was around 8.5 and 70 degrees C, respectively. The Michaelis constants
      for inosine, guanosine, and ribavirin were 1.43 mM, 2.44 mM and 2.08 mM,
      respectively, at 40 degrees C. This enzyme appeared to be a SH enzyme because it
      was inactivated by SH reagents, p-chloromercuribenzoate and N-ethylmaleimide, and
      HgCl2. In addition, this enzyme was completely inactivated by AgNO3 and was
      slightly inhibited by CuSO4. It showed nucleoside-phosphorolyzing activity toward
      inosine, 2'-deoxyinosine, 2',3'-dideoxyinosine, guanosine, 2'-deoxyguanosine, and
      xanthosine. However, adenosine and its derivatives could not be phosphorolyzed.
      This enzyme could not also phosphorolyze various 5'-mononucleotides. According to
      the amino terminal sequence analysis, the twenty residues from the amino terminal
      end of this enzyme were identified as follows: MTVNWNETRS-FLECKMQAKPE.

PMID- 1368698
TI  - Solid-phase synthesis of crystalline monellin, a sweet protein.
AB  - The sweet protein, monellin, consists of two noncovalently associated polypeptide
      chains, the A chain of 44 amino acid residues and the B chain of 50 residues. The
      B chain was synthesized by the stepwise Fmoc solid-phase method in an overall
      yield of 6.2%. The synthetic B chain was combined with the synthetic A chain,
      which was left over from a previous work, to give monellin in a yield of 25.7%.
      The synthetic monellin was approximately 4000 times as sweet as sucrose, while
      the previously synthesized [Asn49, Glu50] B-chain monellin was also approximately
      4000 times as sweet as sucrose. Exchanging Glu49 and Asn50 in the B chain did not
      affect the sweetness potency. Crystallization was performed by a vapor diffusion
      method.

PMID- 1368699
TI  - Enhanced production of antibiotics by Pecilomyces lilacinus under alkaline
      conditions associated with morphological change.
AB  - The production of the group of peptide antibiotics called No. 1907 by
      Paecilomyces lilacinus was stabilized and enhanced by mono-spore isolation
      followed by strain improvement, and the production seemed to be related to a
      morphological change of the strain. Unstable and a low productivity (below 10
      micrograms/ml) of the antibiotics No. 1907 by P. lilacinus was greatly improved
      up to 140 micrograms/ml by successive mono-spore isolation along with
      mutagenization. Alkaline conditions caused by adding Na2CO3, K2CO3, NaHCO3 or
      KHCO3 were essential to obtain high production of the antibiotics following
      simultaneous morphological change of the cells from filamentous mycelia to round
      arthroconidia. Resting cell experiments showed that a significant amount of
      antibiotics (213 micrograms/ml) was synthesized by the filamentous cells along
      with their morphological change to arthroconidia in the presence of glucose under
      the alkaline conditions.

PMID- 1368700
TI  - Identification of Mycoplasma hyopneumoniae with a DNA probe.
AB  - From a genomic library of Mycoplasma hyopneumoniae a 1.3 kb DNA fragment was
      cloned which showed specific Southern hybridization and dot hybridization with
      the type strain of several porcine and bovine Mycoplasma species. This probe
      selectively recognized M. hyopneumoniae sequences in purified DNA or in broth
      grown organisms. The 35S-labelled probe could detect as little as 100 pg of DNA
      or 10(5) colour changing units. This is a possible alternative diagnostic
      procedure for enzootic pneumonia of pigs.

PMID- 1368701
TI  - Lysosomal enzymes produced by immobilized Tetrahymena thermophila.
AB  - The ciliated protozoon Tetrahymena thermophila was immobilized for production of
      secreted lysosomal enzymes in two ways. Cells entrapped in solid Ca-alginate
      spheres survived but were unable to grow and multiply. However, when encapsulated
      in hollow Ca-alginate spheres Tetrahymena multiplied well, reaching 0.9 x 10(7)
      cells/ml. These immobilized cells secreted large amounts of lysosomal enzymes
      when the medium was changed daily. This system was transferred to a reactor scale
      using a conical bubble column reactor for semicontinuous cultivation of the
      encapsulated cells. Under these conditions alpha-glucosidase, beta-glucosidase,
      beta-hexosaminidase and acid phosphatase were produced for at least 4 weeks. The
      hollow spheres were stable for 3 months and contained living and secreting
      Tetrahymena cells during this time. Immobilized T. thermophila cells can thus
      serve as a good source for production of commercially interesting enzymes.

PMID- 1368702
TI  - High-performance liquid chromatographic measurement of tryptophan in blood,
      tissues, urine, and foodstuffs with electrochemical and fluorometric detections.
AB  - A rapid and convenient measurement of tryptophan in whole blood, serum, liver,
      brain, urine, and alkaline hydrolysates of proteins and foodstuff was done by
      high-performance liquid chromatography. The sample preparation was simply
      homogenized or mixed in a 5% trichloroacetic acid solution and a sample of the
      supernatant was injected onto a column after filtration with a 0.45-micron
      filter. The method used a Chemcosorb 5-ODS-H column (particle size, 5 microns,
      150 x 4.6 mm i.d.) eluted with 20 mM potassium dihydrogen phosphate (pH adjusted
      to 3.7 by the addition of phosphoric acid) containing 1 g/l of sodium heptane
      sulfonate and 3 mg/l EDTA.2Na-acetonitrile (93:7, v/v) at a flow rate of 1.5
      ml/min. The tryptophan contents in whole blood, serum, liver, and brain were
      electrochemically estimated at +1000 mV vs. Ag/AgCl, the detection limit being
      0.2 pmol (40.84 pg) at a signal-to-noise ratio of 5:1. The tryptophan contents in
      urine, proteins, and foodstuff were fluorometrically estimated with an excitation
      wavelength of 280 nm and with an emission wavelength of 340 nm, the detection
      limit being 20 pmol (4.08 ng) at a signal-to-noise ratio of 5:1. Tryptophan was
      eluted at about 10.5 min. The total analysis time was about 12 min.

PMID- 1368703
TI  - Cloning and nucleotide sequences of the AccI restriction-modification genes in
      Acinetobacter calcoaceticus.
AB  - The genes of the AccI restriction-modification system specific for GT(A/C)
      (G/T)AC were cloned from the chromosomal DNA of Acinetobacter calcoaceticus, and
      their nucleotides sequenced. The restriction and modification genes coded for
      polypeptides with calculated molecular weights of 42,494 and 63,078,
      respectively. Both the enzymes were coded by the same DNA strand and the
      restriction gene was upstream of the methylase gene, separated by 2 bp. The
      restriction gene was significantly expressed in E. coli cells, so that the AccI
      restriction endonuclease could be purified to homogeneity. Analysis by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration indicated
      that the catalytically active form of the endonuclease was tetrameric. Sequence
      comparison with related enzymes indicated that AccI methylase contained a segment
      of tetra-amino acids, NPPY, characteristic of N6-adenine methylases. In addition,
      some homologous regions were found in the sequence of HincII methylase specific
      for GT(C/T) (A/G)AC.

PMID- 1368704
TI  - Signal peptide of the colicin E2 lysis protein causes host cell death.
AB  - Colicin E2 is encoded by the SOS-inducible colicin operon of plasmid ColE2-P9.
      Highly induced colicin E2 is excreted from the E. coli host cell, accompanied by
      quasi-lysis and cell death. These three events are all directed by the colicin
      lysis protein that comprises the signal peptide and a small mature lipoprotein.
      We constructed a mutant lysis gene encoding its complete signal peptide with
      addition of two external amino acids at the C-terminus. By using this mutant
      peptide as a reference, the wild type lysis signal peptide was identified and
      shown to remain quite stable after the cleavage. This mutant peptide also mimics
      the cleaved-off signal peptide avoiding the influence of the mature lysis
      lipoprotein, and suggested that cell death by the lysis protein, but neither
      colicin excretion nor quasi-lysis, is decided by the nature of its signal region.

PMID- 1368705
TI  - Molecular cloning and analysis of nucleotide sequence of the Bacillus subtilis
      lysA gene region using B. subtilis phage vectors and a multi-copy plasmid,
      pUB110.
AB  - A 3.8-kb EcoRI-fragment containing the lysA gene [diaminopimelate (DAP)
      decarboxylase] of Bacillus subtilis has been cloned into B. subtilis phage phi
      105 and its nucleotides sequenced. The nucleotide sequence of a 3,762 bp stretch
      contained three open reading frames (ORF1, ORF2, and ORF3) in one orientation and
      another open reading frame (ORF4) in the opposite orientation. ORF2 coded for the
      lysA gene based on the complementation of a B. subtilis lys auxotroph and on the
      fact that the predicted amino acid sequence (440 amino acids with a molecular
      weight of 48,876) of ORF2 shared a 29.7%, 38.3%, and 32.9% identity with the
      sequences of Escherichia coli, Corynebacterium glutamicum and Pseudomonas
      aeruginosa lysA genes, respectively. ORF1, ORF3, and ORF4 did not correspond to
      E. coli lysR. Based on the comparison of the B. subtilis lysA sequence with a
      sequence of the DAP-decarboxylase gene cloned into pUB110 (Yamamoto et al.,
      Nucleic Acids Res., 17, 10105 (1989], it was found that the lys gene in the
      plasmid was fused with the dnaN gene in its COOH-terminal region.

PMID- 1368706
TI  - Development of a new protein- and hormone-free medium for hybridoma cultivation.

PMID- 1368707
TI  - Large-scale purification and refolding of recombinant eel growth hormone.

PMID- 1368708
TI  - Changes in specificities of human monoclonal antibodies by introduction of drug
      resistance gene into hybridomas.

PMID- 1368709
TI  - Analysing lymphokine-receptor interactions of IL-1 and IL-2 by recombinant-DNA
      technology.
AB  - The development of lymphokines as pharmaceutical agents is at the forefront of
      current biotechnological research. Lymphokines exert their regulatory action on
      cellular function through interaction with cell-surface receptors. An
      understanding of the biochemical nature of these molecular interactions should
      facilitate the design of small peptide analog pharmaceuticals which mimic
      lymphokines or their receptors.

PMID- 1368710
TI  - Cloning and sequencing of a cyclodextrin glucanotransferase gene from Bacillus
      ohbensis and its expression in Escherichia coli.
AB  - A cyclodextrin glucanotransferase (CGTase) gene of Bacillus ohbensis was cloned
      in Escherichia coli and the nucleotide sequence was determined. A single open
      reading frame (2112 bp) with a TTG codon as an initiator was identified that
      encodes a typical signal peptide of 29 amino acids followed by the mature enzyme
      (675 amino acids), of which the partial amino acid sequences of the N-terminal
      region and some lysyl-endopeptidase fragments were determined by Edman
      degradation. The CGTase gene was expressed in E. coli under control of the lac
      promoter only when the upstream region containing a long inverted repeat
      structure (located at -108 to -67 bp from the initiation codon) was deleted.
      Substitution of an ATG codon for the initiation TTG triplet doubled the
      expression of the CGTase gene in E. coli. Enzyme preparations purified from the
      culture supernatant of B. ohbensis and from the periplasmic fraction of the E.
      coli transformant exhibited the same molecular weight (Mr) and enzymatic
      properties as follows: Mr, 80,000; optimum pH for activity, 5.0 (and a suboptimum
      at 10.0); stability between pH 6.5 and 10.0; optimum temperature for activity, 55
      degrees C; and stability below 45 degrees C. The yields of the products from
      starch as the substrate were 25% for beta- and 5% for gamma-cyclodextrin.

PMID- 1368711
TI  - Enzymatic properties of dipeptidyl carboxypeptidase from Bacillus pumilus.
AB  - Enzymatic properties of dipeptidyl carboxypeptidase (DCP) from Bacillus pumilus
      were investigated. The enzyme was more active on tri- and tetrapeptides than
      angiotensin-converting enzyme (ACE) from rabbit lung. The presence of chloride
      ion is essential for the hydrolysis. The Km value of angiotensin I for the enzyme
      was 0.119 x 10(-3) M. The enzyme was not inhibited by the mammalian ACE
      inhibitors lisinopril and enalaprilat. The enzyme is readily inhibited by EDTA
      but restored by Co2+, Mn2+, and Zn2+. Therefore, it seems to be a zinc-metallo
      protease.

PMID- 1368712
TI  - The amino acid sequence of lysozyme from kalij pheasant (Lophura leucomelana) egg
      white.
AB  - The amino acid sequence of kalij pheasant lysozyme has been analyzed. From the
      comparison of the tryptic peptide pattern of kalij pheasant lysozyme and maps
      from other bird lysozymes followed by the sequencing of tryptic peptides, the
      amino acid sequence of kalij pheasant was found to be:
      KVYGRCELAAAMKRLGLDNYRGYSLGNWVCAAKYESNFNTHATNRNTDGSTDYGIL-
      QINSRWWCNDGKTPGSRNLCHIPCSALLSSDITASVNCAKKIVSDGNGMNAW- VAWRNRCKGTDVSVWTRGCRL. This
      sequence had 9 amino acid substitutions compared with hen egg-white lysozyme. Two
      of these substitutions, positions 34 and 121, were newly detected in phasianid
      birds. The protein genealogy of phasianid bird lysozymes showed some discordance
      with the morphological classification of these birds.

PMID- 1368713
TI  - The amino acid sequence of reeves' pheasant (Syrmaticus reevesii) lysozyme.
AB  - The amino acid sequence of reeves' pheasant lysozyme was analyzed.
      Carboxymethylated lysozyme was digested with trypsin and resulting peptides were
      analyzed using the DABITC/PITC double coupling manual Edman method. The
      established amino acid sequence had seven substitutions, Tyr3, Leu15, His41,
      His77, Ser79, Arg102, and Asn121, compared with hen egg-white lysozyme. Ser79 was
      the first found in a bird lysozyme. A substitution in the active site was found
      in position 102 which has been considered to participate in the substrate binding
      at subsites A-C.

PMID- 1368714
TI  - Purification and some properties of a thermostable metal proteinase produced by
      Thermomicrobium sp. KN-22 strain.
AB  - An extreme thermophile that produces a heat-stable proteinase was isolated from
      hot-spring water and classified as Thermomicrobium sp. KN-22 (growth temperature,
      50-83 degrees C; and optimum growth temperature, 70 degrees C). The proteinase
      was purified from the culture broth of this strain by fractionation with ammonium
      sulfate, chromatography on columns of DEAE-cellulose and CM-Sepharose CL-6B, and
      HPLC on TSKgel CM-5PW. The purified enzyme gave a single band on SDS
      polyacrylamide gel electrophoresis and a single peak after HPLC (yield 8.8%). The
      enzyme had maximum activity at pH 8.5 and at 75 degrees C and it was stable up to
      60 degrees C. The molecular weight of the enzyme was 35,000 by SDS-PAGE. Since
      the enzymatic activity was completely inhibited by EDTA, o-phenanthroline, and
      phosphoramidon, it appears that the enzyme is a metal proteinase.

PMID- 1368715
TI  - Characterization of the leader peptide of an endo-type cellulase produced by an
      alkalophilic Streptomyces strain.
AB  - An endo-type semi-alkaline cellulase (CMCase I) produced by an alkalophilic
      Streptomyces strain has an extraordinarily long leader peptide of about 70 amino
      acids (aa), which can be grouped into four distinct regions, an NH2-terminal
      region (13 aa), an Arg-cluster region (13 aa), a hydrophobic region (23 aa), and
      an Ala/Pro-repeat region (12 aa). For identification of the function of each part
      of the leader peptide for secretion of the enzyme, mutation in the leader peptide
      were generated by site-directed mutagenesis using the cloned gene, and the mutant
      genes were expressed in a cellulase-negative mutant strain, Streptomyces lividans
      HN1. Although all the alterations in the leader peptide, except for one case,
      decreased secretion to various extents, in S. lividans, the following conclusions
      were obtained. Comparison of the intra- and extra-cellular enzyme activities of
      the mutants suggested that the Arg-cluster region was essential in secretion of
      the cellulase. Deletion of 8 amino acids rich in threonine and proline in the NH2
      terminal region enhanced the secretion to a small extent. Deletion of the Ala/Pro
      repeat region had almost no effect on secretion.

PMID- 1368716
TI  - Evidence that more than one gene encodes n-alkane-inducible cytochrome P-450s in
      Candida maltosa, found by two-step gene disruption.
AB  - An n-alkane-assimilating yeast, Candida maltosa, has a diploid genome. Probed
      with the previously isolated gene of n-alkane-inducible cytochrome P-450 (P
      450alk), its allelic gene had been isolated, its nucleotides sequenced, and the
      interallelic divergence examined. Using one of the allelic genes, we disrupted
      the two alleles of the cytochrome P-450alk gene by a two-step gene disruption
      system. Surprisingly, the disruptant still assimilated n-alkane and contained n
      alkane-inducible cytochrome P-450. This result indicates that, other than the
      disrupted two alleles, there is at least one other gene that encodes an n-alkane
      inducible cytochrome P-450.

PMID- 1368717
TI  - Purification and properties of aminopeptidase C from chicken skeletal muscle.
AB  - Aminopeptidase C was purified from fresh chicken skeletal muscle by ammonium
      sulfate fractionation, and by successive chromatography on DEAE-cellulose,
      Ultrogel AcA 34, DEAE-cellulose again, and an alanine AH-Sepharose 4B affinity
      column twice. The purified enzyme migrated as a single band by SDS-PAGE.
      Aminopeptidase C was purified about 300-fold over the crude extract with a yield
      of 0.6%. The molecular weight of this enzyme was found to be 185,000 by gel
      filtration in a Sepharose 6B column and 92,000 by SDS-PAGE. The optimum pH for
      the hydrolysis of L-leucine beta-naphthylamide was 6.0-7.0, the enzyme being
      stable in the range of pH 6.5-8.0. The activity of this enzyme was strongly
      inhibited by EDTA and puromycin, and was high against the beta-naphthylamide
      derivatives of Lys, Leu, Ala and Met. The enzyme was more active towards tri- and
      tetrapeptides than towards dipeptides.

PMID- 1368718
TI  - Purification and some properties of sucrose phosphorylase from Leuconostoc
      mesenteroides.
AB  - Sucrose phosphorylase (EC 2.4.1.7) was purified to homogeneity from Leuconostoc
      mesenteroides cells with a specific activity of 173.8 units per mg protein by
      ammonium sulfate fractionation, anion exchange HPLC on TSKgel DEAE-5PW, and
      hydrophobic HPLC on TSKgel Ether-5PW. The purified enzyme was an acidic protein
      having an isoelectric point of pH 4.6 and s0(20),W of 4.34S. The molecular weight
      of this enzyme was estimated to be 56,400 by sedimentation equilibrium, 55,000 by
      SDS-polyacrylamide gel electrophoresis, and HPLC gel filtration on TSKgel
      G3000SW, suggesting that the enzyme is a monomeric protein. With regard to
      molecular weight, amino acid composition, and N-terminal amino acid sequence of
      30 residues, this enzyme is close to the glucosyltransferase A of Streptococcus
      mutans.

PMID- 1368719
TI  - Efficient production of Taka-amylase A by Trichoderma viride.
AB  - An efficient heterologous protein production system was developed in Trichoderma
      viride, a very efficient cellulase producer. An expression vector containing the
      Taka-amylase A gene from Aspergillus oryzae, which was fused to the strong
      promoter and signal peptide sequence of the cellobiohydrolase 1 gene (cbh1) of T.
      viride, and the hygromycin B resistance gene was used to transform protoplasts of
      T. viride. Using hygromycin B resistance, a frequency of 3 transformants per
      microgram DNA on average was obtained. One transformant showed highly elevated
      alpha-amylase production, 1.0 g/l, which was shown to be under the control of the
      cbh1 gene promoter. Analysis of the chromosomal DNA of the transformant showed
      the integration of more than one copy of the vector.

PMID- 1368720
TI  - Solid-phase synthesis of crystalline [Ser41] B-chain monellin, an analogue of the
      sweet protein monellin.
AB  - The sweet protein monellin consists of two noncovalently associated polypeptide
      chains, the A chain of 44 amino acid residues and the B chain of 50 residues.
      Since blocking the free SH group of Cys41 in the B chain or treating the adjacent
      Met42 with CNBr removed its sweetness, this part of the molecule has been
      suggested to be essential for the sweetness. The [Ser41] B chain, an analogue of
      the B chain, was synthesized by the stepwise Fmoc solid-phase method in an
      overall yield of 1.9%. The synthetic B chain analogue was combined with the A
      chain, which was left over from a previous work, to give [Ser41] B-chain monellin
      in a yield of 31.0%. This synthetic monellin analogue was 2000 times as sweet as
      sucrose. Changing the Cys41 residue to the Ser residue significantly decreased
      the sweetness potency and stability of the molecule in solution. Crystallization
      was carried out by a vapor diffusion method.

PMID- 1368722
TI  - Identification of the promoter region of the Taka-amylase A gene required for
      starch induction.

PMID- 1368721
TI  - Purifications and properties of orotidine-phosphorolyzing enzyme and purine
      nucleoside phosphorylase from Erwinia carotovora AJ 2992.
AB  - An orotidine-phosphorolyzing enzyme and a purine nucleoside phosphorylase
      (PNPase) of Erwinia carotovora AJ 2992, which is a potent producer of ribavirin
      (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), an antiviral agent, from
      orotidine and 1,2,4-triazole-3-carboxamide (TCA), were purified 23-fold and 103
      fold, respectively. At each purification step, the orotidine-phosphorolyzing
      enzyme was always co-purified with an uridine phosphorylase (UPase) and its
      activity could not be separated from that of the UPase after it showed as a
      single band on SDS-polyacrylamide gel electrophoresis. These results suggest that
      this enzyme may be identical with UPase. The purified enzyme had a molecular
      weight of 68,000 +/- 2,000, and seemed to be a dimer. The optimal temperatures
      and pH values were 60 degrees C and 6.0 for orotidine phosphorolysis, and 70
      degrees C and 7.0 for uridine phosphorolysis. The Michaelis constants for uridine
      and orotidine were 0.75 mM and 10.87 mM, respectively, at 40 degrees C. The
      PNPase of E. carotovora AJ 2992 had a molecular weight of 58,000 +/- 2,000 and
      seemed to be a dimer. The Michaelis constants for inosine and guanosine were 1.92
      mM and 1.85 mM, respectively, at 40 degrees C. The PNPase was completely
      inactivated by p-chloromercuribenzoate.

PMID- 1368723
TI  - Expression of a putative precursor of pheromone biosynthesis activating
      neuropeptide-I (PBAN-I) of the silkmoth, Bombyx mori, and its conversion to the
      mature peptide, PBAN-I.

PMID- 1368724
TI  - A DNA transformation-competent Arabidopsis genomic library in Agrobacterium.
AB  - We have constructed a nuclear genomic library from the cruciferous plant
      Arabidopsis thaliana ecotype Columbia in a cosmid vector, pLZO3, and a host
      organism, Agrobacterium tumefaciens AGL1, which can directly DNA-transform the
      parent organism, Arabidopsis. The broad host range cosmid pLZO3 carries a
      gentamicin acetyltransferase gene as bacterial selective marker and tandem,
      chimeric neomycin and streptomycin phosphotransferase genes as plant selective
      markers. Agrobacterium AGL1 carries the hypervirulent, attenuated tumor-inducing
      plasmid pTiBo542 from which T-region DNA sequences have been precisely deleted,
      allowing optimal DNA transformation of many dicotyledonous plants. Agrobacterium
      AGL1 also carries an insertion mutation in its recA general recombination gene,
      which stabilizes the recombinant plasmids. The Arabidopsis genomic library
      consists of some 21,600 clones gridded onto 96-well microtiter dishes and, if
      random, carries at least three genomic equivalents. When probed for the presence
      of several Arabidopsis low copy-number genes, the genomic library seems
      representative. As with the unicellular organisms Escherichia coli and
      Saccharomyces cerevisiae, this DNA transformation competent genomic library
      should expedite gene isolation, by gene rescue, in multicellular organisms like
      Arabidopsis.

PMID- 1368725
TI  - Commercial levels of chymosin production by Aspergillus.
AB  - We have increased the production of bovine chymosin in Aspergillus niger var.
      awamori to more than one gram per liter of secreted authentic enzyme by combining
      a mutagenesis protocol with a novel robotic screening program. Analysis of the
      superior chymosin producing strains indicated that they have enhanced
      capabilities to secrete extracellular proteins.

PMID- 1368726
TI  - Cloning and nucleotide sequence of the KHS killer gene of Saccharomyces
      cerevisiae.
AB  - A 5.3-kbp fragment of the KHS gene was cloned from a genomic bank of
      Saccharomyces cerevisiae No. 115 constructed with an E. coli as the host and
      YEp13 as the vector. A non-killer yeast strain was transformed to a killer strain
      with the multi-copy vector containing the KHS gene, and the transformant could
      secrete 3-4 times more killer toxin into culture media than the donor, strain No.
      115. The KHS toxin was purified 80-fold from the culture filtrate by gel
      filtration and column chromatography. The nucleotide sequence of a 2.8-kbp
      fragment of the KHS DNA that was enough for the expression of the killer activity
      was identified, and we found an open reading frame consisted of 2124 bp.
      Comparison of the open reading frame and N-terminal amino acid sequence of
      purified KHS toxin, suggested that the presumed peptide from the KHS gene might
      be processed between 36Gln and 37Ala before secretion.

PMID- 1368727
TI  - Purification and properties of a xylanase from Cellvibrio gilvus that hydrolyzes
      p-nitrophenyl cellooligosaccharides.
AB  - An enzyme component that hydrolyzes pNP-G2 but not CMC has been isolated from a
      culture broth of Cellvibrio gilvus by a multi-step procedure involving Butyl
      Toyopearl, DEAE-Toyopearl, and CM-Toyopearl chromatographies. The purified enzyme
      gave a single protein band on native, SDS-, and IEF-PAGE. The enzyme had a
      molecular weight of 40,000, an isoelectric point of 5.0, an optimum pH of 6.5,
      and an optimum temperature of 55 degrees C. It was stable from pH 4.0 to 9.0 at
      37 degrees C for 1 hr and below 50 degrees C for 30 min. It hydrolyzed agluconic
      bonds not only of pNP-G2 but also of pNP-G3, pNP-G4, and pNP-G5.
      Cellooligosaccharides with D.P. of 3 to 5 were not hydrolyzed at all. Instead,
      the enzyme hydrolyzed xylan 4 times as fast as pNP-G2. Both HgCl2 and p
      chloromercuribenzoic acid inhibited the two activities completely. Xylan
      inhibited the hydrolysis of pNP-G2 competitively. From these results, the
      purified enzyme was considered to be a unique xylanase that hydrolyzed the
      agluconic bonds of pNP-Gn.

PMID- 1368728
TI  - Purification and characterization of a novel lyase from Cellulomonas sp. that
      degrades Fusarium and Gibberella acidic polysaccharides.
AB  - A Cellulomonas sp. isolated from soil produced a novel lyase that degraded the
      acidic polysaccharide of Fusarium sp. M7-1 with the formation of mannose and O
      beta-D-mannopyranosyl-(1----2)-D-mannose. DEAE-Toyopearl 650M column
      chromatography showed three lyase activity peaks (fractions I, II, and III). The
      major fraction was purified to homogeneity by polyacrylamide gel electrophoresis
      analysis, and its molecular weight was 74,000. The optimum pH was 6.5 to 8.0 and
      the stable pH range was 6.0 to 8.0. The purified enzyme did not degrade
      glucuronic or galacturonic acid-containing polysaccharides such as chondroitin,
      hyaluronic acid, pectin, or pectic acid. However, the purified enzyme
      specifically degraded various Fusarium and Gibberella acidic polysaccharides, and
      unsaturated sugars were produced with the release of mannose and O-beta-D
      mannopyranosyl-(1----2)-D-mannose. These results suggest that the acidic
      polysaccharides derived from Fusarium and Gibberella have similar structures.

PMID- 1368729
TI  - Primary structures of N-linked oligosaccharides of momordin-a, a ribosome
      inactivating protein from Momordica charantia seeds.
AB  - The structures of the N-linked oligosaccharides of momordin-a, which is a
      ribosome-inactivating protein from the seeds of Momordica charantia, were
      analyzed. First, the N-linked oligosaccharides of this glycoprotein were
      liberated by hydrazinolysis. After N-acetylation, the reducing ends of the
      oligosaccharides were coupled with 2-aminopyridine and the pyridylamino (PA-)
      derivatives were purified by gel filtration and high performance liquid
      chromatography (HPLC) on an ODS-silica column. Three kinds of oligosaccharide
      fractions were separated by HPLC. The structure of each oligosaccharide isolated
      was analyzed by a combination of sugar component analysis, exoglycosidase
      digestion, another kind of HPLC using an amide-silica column, and 500-MHz 1H NMR
      spectroscopy. The structures of two main oligosaccharides were established to be:
      [Formula; see text] and [Formula; see text]. These two oligosaccharides were the
      first examples having xylose (or fucose) but no alpha-mannosyl linkage among the
      N-linked oligosaccharides of glycoproteins from both animal and plant origins.

PMID- 1368730
TI  - Transfer reaction catalyzed by exo-beta-1,4-galactanase from Bacillus subtilis.
AB  - A transfer reaction catalyzed by an exo-beta-1,4-galactanase from Bacillus
      subtilis was studied. The enzyme had a broad acceptor specificity and transferred
      galactobiosyl residues to acceptors such as various alcohols, including hydroxy
      benzenes and saccharides. Transfer products of glycerol formed by the enzyme were
      compared with those formed by Escherichia coli beta-galactosidase and by
      Penicillium citrinum endo-galactanase. E. coli enzyme transferred 90% of
      galactose residues to the primary hydroxyl groups of glycerol and P. citrinum
      endo-enzyme transferred 80% of saccharide residues to the secondary hydroxyl
      group. The B. subtilis exo-galactanase was less specific than the other two
      enzymes and formed two products (1-DG and 2-DG) with a 2-DG/1-DG ratio of about
      2. The structures of the saccharides were examined by 13C-nuclear magnetic
      resonance analysis and by enzymatic hydrolysis. 1-DG and 2-DG were elucidated to
      be O-beta-D-galactosyl-(1----4)-O-beta-D-galactosyl-(1----1)-glycerol and O-beta
      D-galactosyl-(1----4)-O-beta-D-galactosyl-(1----2)-glycerol, respectively. The
      efficiency of the transfer reaction was measured at various concentrations of
      glycerol using galactotriose as a donor. About 40-75% of galactobiosyl residues
      were transferred at an acceptor concentration range of 20-100 mg/ml.

PMID- 1368731
TI  - Dye-sensitized photooxidation of neutral protease from Bacillus subtilis var.
      amylosacchariticus: assignment of histidine residue oxidized.
AB  - The neutral protease of Bacillus subtilis var. amylosacchariticus was
      photooxidized in the presence of methylene blue, by which treatment the enzyme
      was rapidly inactivated. The inactive enzyme was digested with endoproteinase Asp
      N, the resultant peptides were separated by HPLC, and their amino acid sequences
      were compared with those obtained from the unmodified enzyme. Of four peptides
      that contained histidine residues, only the recovery of one peptide was found to
      be decreased by the photooxidation with the appearance of a new peptide.
      Comparisons of amino acid compositions and sequences between these two peptides
      showed that the latter peptide lacked His228 of the former one, indicating that
      His228 was photooxidized. This result suggests that His228 is involved in the
      catalytic reaction of the neutral protease or interaction with substrates.

PMID- 1368732
TI  - Synthesis of the trisaccharide-protein conjugate of the phenolic glycolipid of
      Mycobacterium tuberculosis for the serodiagnosis of tuberculosis.
AB  - The trisaccharide segment of the phenolic glycolipid (PGL) of Mycobacterium
      tuberculosis, 2-O-methyl-3-O-[3-O-(2,3,4-tri-O-methyl-alpha-L-fucopyranosyl)
      alpha-L- rhamnopyranosyl]-alpha-L-rhamnopyranose, was synthesized in the form of
      the p-(2-methoxycarbonylethyl)phenyl glycoside by a stepwise condensation. 2,4-Di
      O-benzyl-3-O-acetyl-alpha-L-rhamnopyranosyl chloride was coupled to p-(2
      methoxycarbonylethyl)phenyl 4-O-benzyl-2-O-methyl-alpha-L-rhamnopyranoside in the
      presence of silver triflate, and 2,3,4-tri-O-methyl-alpha-L-rhamnopyranosyl
      chloride was then coupled to the deacetylated disaccharide by the same procedure.
      The trisaccharide was deblocked and coupled to BSA, giving the neoglycoconjugate
      TB-NT-P-BSA. TB-NT-P-BSA showed its possibility as a useful tool for the
      serodiagnosis of tuberculosis.

PMID- 1368733
TI  - Production and characterization of anti-human insulin antibodies in the hen's
      egg.

PMID- 1368734
TI  - Potent synthetic analogues of angiotensin-converting enzyme inhibitor derived
      from Tuna muscle.

PMID- 1368735
TI  - Amino acid compositions and partial sequences of xylanases from a new subspecies,
      Nocardiopsis dassonvillei subsp. alba OPC-18.

PMID- 1368736
TI  - Specificity of a new metalloproteinase form Penicillium citrinum.

PMID- 1368737
TI  - Purification and properties of a novel surface-active agent- and alkaline
      resistant protease from Bacillus sp. Y.
AB  - In the course of a search for an alkaline stable protease for industrial use, an
      alkaline protease (protease BYA) was isolated from an alkalophilic Bacillus sp.
      Y, and its properties were characterized. Its optimum pH was pH 10.0-12.5, when
      casein was used as a substrate. In addition to the stability of protease BYA at
      pH 6.5-13.0, it was also very stable towards various surface-active agents, such
      as sodium dodecyl sulfate and sodium linear alkylbenzene sulfonate. Protease BYA
      was most active at 70 degrees C. The isoelectric point (pI) of protease BYA was
      about 10.1. Protease BYA was characterized as a serine protease because of its
      sensitivity to phenylmethanesulfonyl fluoride and diisopropyl fluorophosphate.
      The protease seems to be related to proteases of the subtilisin family, such as
      subtilisin BPN', subtilisin Carlsberg, and No. 221 protease.

PMID- 1368738
TI  - Gene encoding a putative zinc finger protein in Synechocystis PCC6803.
AB  - A 5.5-kb HindIII fragment of Synechocystis PCC6803 containing a liverwort
      (ORF316) homolog encoding a putative zinc finger protein was cloned. Nucleotide
      sequence analysis showed that the homology of the amino acid sequence deduced
      from the ORF326 of Synechocystis PCC6803 with the counterparts of a liverwort and
      tobacco was 50% and 46%, respectively. Synechocystis ORF326 also showed 38%
      homology with the dedB gene in Escherichia coli. The gene organization of the
      region in these species of organisms was quite different. This suggests that the
      Synechocystis ORF326 and liverwort ORF316 genes may be related to a common
      regulatory gene, but not photosynthetic gene characteristic to chloroplasts.

PMID- 1368739
TI  - Cloning, nucleotide sequencing, and expression in Escherichia coli of a lipase
      and its activator genes from Pseudomonas sp. KWI-56.
AB  - A lipase gene (lip) and its activator gene (act) on a 2.9 kb BglII-EcoRI fragment
      from Pseudomonas sp. KWI-56 were cloned in Escherichia coli using pUC19 as a
      vector plasmid. From the sequencing results, the open reading frames of the lip
      and the act were found to contain 1092 and 1032 nucleotides, respectively. The
      act existed downstream of the lip with the same orientation. When the lip was
      expressed in E. coli using the lac promoter on the pUC plasmid vector, the lipase
      activity of E. coli carrying both the lip and the act was 200-fold greater than
      that carrying only the lip. This result suggested the act was important in the
      expression of the lip in E. coli.

PMID- 1368740
TI  - Cloning and nucleotide sequence of thermostable lipase gene from Pseudomonas
      fluorescens SIK W1.
AB  - A gene coding for a thermostable lipase of Pseudomonas fluorescens SIK W1 was
      cloned into Escherichia coli JM83 by inserting Sau3AI-generated DNA fragments
      into the BamHI site of pUC19. Twenty colonies with esterase activity on the
      tributyrin agar plate were isolated by screening the constructed Pseudomonas
      fluorescens genomic library. Only one out of the esterase positive 20 colonies
      had lipase activity on the agar plate containing olive oil and Rhodamine-B. The
      complete nucleotide sequence of the lipase gene was identified. The lipase gene
      consists of an open reading frame, 1347bp long, commencing with an ATG start
      codon encoding a polypeptide of 449 amino acid residues and a TGA stop codon.
      Comparison of this lipase amino acid sequence with those from another organisms
      sequenced to data showed the presence of the short homologous region Gly-X-Ser-X
      Gly.

PMID- 1368741
TI  - Use of a triple protease-deficient mutant of Bacillus subtilis as a host for
      secretion of a B. subtilis cellulase and TEM beta-lactamase.
AB  - The mature portion of the TEM beta-lactamase (BLA) gene (bla) derived from pBR322
      was fused with the promoter and signal region of Bacillus subtilis cellulase
      (BSC) gene (bsc), and the productivity was compared with that of the cloned
      native bsc gene, using a wild-type B. subtilis strain and a strain deficient in
      three proteases (i.e., extracellular serine protease, extracellular neutral
      protease, and the major intracellular serine protease) as hosts. The effects of
      the sen, sacQ, and prtR genes, carried on the same plasmids, were tested as for
      the productivities of BSC and BLA. The production of BSC was increased 9-fold by
      using the combination of the triple-protease deficient strain and the sacQ gene,
      compared with that by using the wild-type strain as a host, and no degradation of
      BSC was observed in the triple-protease deficient strain. On the other hand,
      though the production of the BSC-BLA fusion protein increased 2.5-fold in the
      triple-protease deficient strain, the BLA activity was decreased after the cell
      reached the stationary phase of growth, possibly due to some proteolysis. These
      observations show different sensitivity of secretary proteins to cellular
      proteases, and suggest that BLA is decomposed by remaining minor proteases.

PMID- 1368742
TI  - Some properties of a cysteine proteinase inhibitor from corn endosperm.

PMID- 1368743
TI  - Construction of novel expression vectors effective in Pseudomonas cells.

PMID- 1368744
TI  - Enzymic synthesis of 4(5)-O-beta-galactosyl-maltopentaose by Bacillus circulans
      beta-galactosidase.

PMID- 1368745
TI  - A rapid isolation of the unknown 5'-flanking sequence of human CENP-B cDNA with
      polymerase chain reactions.
AB  - We rapidly and efficiently isolated the 5'-region of cDNA encoding the N-terminal
      region of human centromere antigen B (CENP-B) including an ATG methionine codon
      by polymerase chain reactions (PCR). The unknown 5'-flanking sequence of the cDNA
      was amplified using an adaptor-sequence ligated to the 5' end as a universal
      primer sequence. To locate the target fragments, we did an additional PCR with
      another set of two internal primers using samples of the size-fractionated
      products as templates, rather than using the conventional hybridization
      procedure. This approach can further be applied to the analysis of other unknown
      flanking sequences of cDNA or genomic DNA.

PMID- 1368746
TI  - Antitumor activity of some polysaccharides isolated from a Chinese mushroom,
      "huangmo", the fruiting body of Hohenbuehelia serotina.
AB  - Polysaccharides were extracted from a Chinese mushroom, "Huangmo" with hot water
      (FI), 1% ammonium oxalate solution (FII), and 5% sodium hydroxide (FIII) and 20
      more polysaccharides were isolated by ethanol precipitation, ion-exchange
      chromatography, gel filtration, and affinity chromatography. Of the six
      polysaccharides obtained, FI0, FA-1, FA-2, FII-2, FIII-1-b, and FIII-2-b were
      selected on the basis of the results of the antitumor activity test (the Sarcoma
      180/mice, i.p. method). Six fractions which showed relatively high activities
      were examined: FI0, a mixture of galactose-containing heteroglycan and beta-D
      glucan; FA-1 and -2, beta-D-glucan with galactose-containing hetero-glycan and
      protein; FII-2, beta-D-glucan; and FIII-1-b and FIII-2-b, (1----6)-beta-D
      glucosyl branched (1----3)-beta-D-glucan.

PMID- 1368747
TI  - Chemical modification of neutral protease from Bacillus subtilis var.
      amylosacchariticus: assignment of tyrosyl residues iodinated.
AB  - The neutral protease of Bacillus subtilis var. amylosacchariticus (B.
      amylosacchariticus) was iodinated with a 25-fold molar excess of iodine at pH 9.4
      for 3 min at 0 degree C, by which treatment the proteolytic activity toward
      casein was markedly reduced, while the hydrolytic activity toward an N-blocked
      peptide substrate was rather increased. The modified enzyme was digested with
      Staphylococcus aureus V8 protease at pH 8.0 and the amino acid sequences of
      resultant peptides were compared with those obtained from the native enzyme. One
      of the peptides was found to have an amino acid sequence of Thr-Ala-Asn-Leu-Ile
      Tyr-Glu, which corresponds to residue Nos. 153-159 of the enzyme, where Tyr-158
      was identified to be mono-iodotyrosine. The other two peptides were those
      containing Tyr-21 which was mono- and di-iodinated, respectively. Referring to
      nitration experiments on the neutral protease and the active site structure of
      thermolysin, it was concluded that the iodination of Tyr-158 is mainly
      responsible for the activity changes of B. amylosacchariticus neutral protease.

PMID- 1368748
TI  - Isolation and characterization of the alkaline protease gene of Aspergillus
      oryzae.
AB  - The genomic DNA for the alkaline protease (Alp) of the fungus Aspergillus oryzae
      was isolated using synthetic oligonucleotides as hydridization probes, and the
      complete nucleotide sequence was identified. The Alp gene is 1374 nucleotides
      long and contains three introns, one of which is in the pro region and two in the
      mature coding region. Sequences related to the TATA box (TATAAAT) and the CAAT
      box (CCAAAT) were found in the 5'-noncoding region. Primer extension analysis
      showed that three transcriptional start points are present.

PMID- 1368749
TI  - Purification and characterization of beta-N-acetylhexosaminidase from Trichoderma
      harzianum.
AB  - beta-N-Acetylhexosaminidase was produced by Trichoderma harzianum cultivated with
      chitin as the growth substrate. The enzyme was purified 13.2-fold to homogeneity
      by ultrafiltration and sequential chromatography on SP-Toyopearl and Sephacryl S
      200. The molecular weight of the enzyme was estimated to be about 150,000 by gel
      filtration. The pH and temperature optima were 4.0-5.5 and 50 degrees C,
      respectively. The enzyme hydrolyzed N-acetylchitooligosaccharides at the non
      reducing ends to release GlcNAc monomer. The enzyme showed a strict substrate
      specificity to the sugar chains in complex carbohydrates, hydrolyzing only the
      linkage of GlcNAc beta 1-3Gal, but not hydrolyzing the other linkages such as
      GalNAc beta 1-3Gal and GlcNAc beta 1-2Man.

PMID- 1368750
TI  - Characterization of Pseudomonas fluorescens carboxylesterase: cloning and
      expression of the esterase gene in Escherichia coli.
AB  - The Pseudomonas fluorescens gene (estB) that encodes a novel esterase (esterase
      II) was cloned into Escherichia coli JM83. DNA sequencing found a single open
      reading frame of 654 nucleotides. The open reading frame was confirmed by N
      terminal amino acid sequence analysis of the esterase protein. A potential Shine
      Dalgarno sequence is followed by the coding sequence of the estB gene. The amino
      acid sequence deduced from the nucleotide sequence contains the consensus active
      site sequence, G-X-S-X-G, of serine esterases. The enzyme expressed in an E. coli
      clone was purified by ion-exchange chromatography and gel filtration. Homogeneity
      of the purified enzyme was confirmed using SDS-polyacrylamide gel
      electrophoresis. The native enzyme exists as a dimer consisting of two identical
      subunits, each with a molecular weight of 23,000. The results of the experiments
      for identifying substrate specificity and the inhibitor studies suggest that this
      enzyme is a carboxylesterase (EC 3.1.1.1) and a serine residue is present at the
      active site of the esterase, as in the esterases of animal tissues.

PMID- 1368751
TI  - Random point mutation analysis of the signal peptide cleavage area of Bacillus
      stearothermophilus alpha-amylase.

PMID- 1368752
TI  - Generation of human-mouse hybridoma secreting human IgM class anti
      neocarzinostatin antibody and its application to hybrid hybridoma.

PMID- 1368753
TI  - Chemical structure of xylan in cotton-seed cake.

PMID- 1368754
TI  - Purification and characterization of rice peroxidases.
AB  - Four peroxidase components, named RP-2, 4, 6, and 7, were isolated from rice
      (Oryza sativa L.) green leaves. Isoelectric focusing indicated that each
      preparation was homogeneous. The molecular weights of RP-2, 4, 6, and 7 estimated
      by SDS-PAGE were 48,000, 48,000, 40,000, and 39,500, and their isoelectric points
      were 5.4, 8.1, 9.3, and 9.2, respectively. The activity of every preparation was
      maximum around pH 5.0. Antisera against these purified enzymes were raised in
      rabbits. Ouchterlony double diffusion tests with these antisera suggested that RP
      6 and 7 were immunochemically identical and RP-2 and 4 were identical in parts
      and that RP-6 and 7 were quite different from RP-2 and 4. Analysis of the N
      terminal amino acid sequences also showed that these peroxidase components were
      classified into two groups. The polymerase chain reaction showed that RP-2 and/or
      RP-4 contained an active central region, which is homologous to other plant
      peroxidases.

PMID- 1368755
TI  - A lectin from the mushroom Pholiota aurivella.
AB  - A lectin was isolated from the fruiting bodies of Pholiota aurivella by
      preparative PAGE and named PAA (Pholiota aurivella agglutinin). PAA was a
      polymeric protein of more than several hundred kDa consisting of 18-kDa subunits.
      The amino acids were sequenced from the N-terminus of the lectin; they were
      YSVTTPNSVKGGTNQG. PAA agglutinated human erythrocytes regardless of blood type
      equally and Pronase treatment of erythrocytes increased the sensitivity to
      agglutination by the lectin. In a hemaggluting inhibition assay, none of the mono
      and oligosaccharides used affected agglutination by the lectin. Among
      glycoproteins, asialofetuin was the best inhibitor. This is first isolated and
      characterized lectin from the family Strophariaceae.

PMID- 1368756
TI  - Utilization of trans-activated T4 uvsY regulatory signal for a high yield of
      cloned gene products.
AB  - We established an efficient system for a high-level production of foreign gene
      products in Escherichia coli using a trans-activated gene expression under the
      control of a phage T4 regulatory signal cloned in a plasmid by T4 phage
      infection. The transcriptional and translational signal of the T4 uvsY gene
      cloned in a plasmid was fused translationally with the coding region of the lacZ
      gene. When E. coli cells carrying the uvsY-lacZ plasmid were infected with
      cytosine-substituting T4 phage at a multiplicity of infection of 5, the amount of
      beta-galactosidase increased about 2-fold (trans-activation) over that without
      phage infection. We examined conditions for the high-level production of a trans
      activated gene product. We found that a large number of T4-infected cells in a
      lysis-inhibition state could be obtained by a low multiplicity of infection with
      cytosine-substituting T4 phage. Thus it is now possible to attain a high yield of
      the trans-activated gene products. We discuss the advantage of the trans
      activated T4 uvsY regulatory signal for production of foreign products.

PMID- 1368758
TI  - Characterization of a beta-glucosidase encoded by a gene from Cellvibrio gilvus.

PMID- 1368757
TI  - A novel expression system for production of a labile protein in Escherichia coli
      by infection with cytosin-substituting T4 phage.
AB  - A novel expression system was developed for the high level production of a labile
      protein in Escherichia coli. The regulatory signal of bacteriophage T4 uvsY gene
      was fused in frame with the coding region of human ventricular myosin alkali
      light chain (VLC1) gene. Expression from the regulatory signal was enhanced and
      continued in a lysis-inhibition state by infection with a cytosine-substituting
      T4 phage mutant. VLC1 protein was produced at a low level without infection
      because of its instability in the cells. Although the productivity was partly
      improved in a lon-deficient mutant without infection, it was improved about 100
      fold with T4 phage infection. T4 phage produces protease inhibitor(s) (pin gene
      product) against proteases of host cell including the lon gene product (protease
      La).

PMID- 1368759
TI  - Synthesis of 5-keto-5-oxime derivatives of milbemycins and their activities
      against microfilariae.
AB  - Starting from milbemycin D (1), milbemycin A4 (2) and milbemycin A3 (3), a series
      of 5-keto-5-oxime derivatives were synthesized by selective oximation at the
      alpha,beta-conjugated carbonyl function of the 5-ketomilbemycins (4-6). The
      activities of the synthesized compounds were studied in dogs naturally infested
      with microfilariae of Dirofilaria immitis. The 5-keto-5-oximes of milbemycin D
      (7), A4 (8) and A3 (9) had quite high efficacy to control the microfilariae and
      more potency than their parents, while the 5-O-acyl oximes (11-15) also exhibited
      high activity.

PMID- 1368760
TI  - Amino acid sequences of the two smallest trypsin inhibitors from sponge gourd
      seeds.

PMID- 1368761
TI  - NMR spectra of partially deacetylated chitotrisaccharides.

PMID- 1368762
TI  - Structures of new cyclic peptides in young unshiu (Citrus unshiu Marcov.), orange
      (Citrus sinensis Osbeck.) and amanatsu (Citrus natsudaidai) peelings.
AB  - Four cyclic peptides were isolated from young unshiu (unripe fruit), orange and
      amanatsu peelings, and their structures were established on the basis of FAB-MS
      (CID method) and 2D-NMR spectroscopic data, and by chemical evidence. They were
      each found to consist of seven or eight amino acids.

PMID- 1368763
TI  - Enzymic production of sweet stevioside derivatives: transglucosylation by
      glucosidases.
AB  - For the purpose of improving sweetness and a further study on the structure
      sweetness relationship of steviol glycosides, transglycosylation of stevioside by
      a variety of commercial glucosidases was investigated. It was revealed that two
      alpha-glucosidases gave glucosylated products. Transglucosylation of stevioside
      by Pullulanase and pullulan exclusively afforded three products, 13-O-[beta
      maltotriosyl-(1----2)-beta-D-glucosyl]-19-O-beta-D-g luc osyl- steviol (1), 13-O
      [beta-maltosyl-(1----2)-beta-D-glucosyl]-19-O-beta-D-glucosyl- steviol (2) and 13
      O-beta-sophorosyl-19-O-beta-maltotriosyl-steviol (3). All of these products have
      already been obtained by trans-alpha-1,4-glucosylation of stevioside by the
      cyclodextrin glucanotransferase starch system, and 1 and 2 have been proven to be
      tasty and potent sweeteners. Transglucosylation of stevioside by Biozyme L and
      maltose afforded three new products, 4, 5 and 6, the structures of these
      compounds being elucidated as 13-O-beta-sophorosyl-19-O-beta-isomaltosyl-steviol
      (4), 13-O-[beta-isomaltosyl(1----2)-beta-D-glucosyl]-19-O-beta-D-glucosyl-
      steviol (5) and 13-O-[beta-nigerosyl-(1----2)-beta-D-glucosyl]-19-O-beta-D-
      glucosyl-steviol (6). A significantly high quality of taste was evaluated for 4.

PMID- 1368764
TI  - Involvement of NH2-terminal pro-sequence in the production of active aqualysin I
      (a thermophilic serine protease) in Escherichia coli.
AB  - Aqualysin I is a heat-stable subtilisin-type protease produced by Thermus
      aquaticus YT-1. The precursor of aqualysin I consists of four domains: an NH2
      terminal signal peptide, an NH2-terminal pro-sequence, a protease domain, and a
      COOH-terminal pro-sequence. In Escherichia coli cells harboring recombinant
      plasmid carrying the aqualysin I gene, proteolytic activity is obtained on
      treatment at 65 degrees C and mature enzyme is detected. In the case of mutant
      genes containing partial deletions in the NH2-terminal pro-sequence, no
      proteolytic activity was detected and the precursor protein was found to be
      unstable in E. coli. These results indicate that the NH2-terminal pro-sequence is
      required to produce the active enzyme by stabilizing the precursor structure.
      Amino acid substitutions in the conserved sequence of the NH2-terminal pro
      sequence found among subtilisin-type proteases made the processing faster
      compared with the wild type.

PMID- 1368765
TI  - Transformation of Penicillium urticae with plasmids containing the hygromycin B
      resistance gene.
AB  - A transformation system with efficiencies between 6 and 50 stable transformants
      per micrograms of DNA was developed for Penicillium urticae J1 (ATCC48163) using
      hygromycin B-resistant plasmids containing or not containing fragments of the P.
      urticae genome. The tandem repeated integration and/or random integration of
      vector DNA were observed. Although P. urticae was unable to grow in the presence
      of 200 micrograms/ml hygromycin B, the transformants were resistant to more than
      5 mg/ml of hygromycin B.

PMID- 1368766
TI  - Purification and properties of thermostable tryptophanase from an obligately
      symbiotic thermophile, Symbiobacterium thermophilum.
AB  - A thermostable tryptophanase was extracted from a thermophilic bacterium,
      Symbiobacterium thermophilum strain T, which is obligately symbiotic with the
      thermophilic Bacillus strain S. The enzyme was purified 21-fold to homogeneity
      with 19% recovery by a series of chromatographies using anion-exchange,
      hydroxylapatite, hydrophobic interaction, and MonoQ anion-exchange columns. The
      molecular weight of the purified enzyme was estimated to be approximately 210,000
      by gel filtration, while the molecular weight of its subunit was 46,000 by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, which indicates that the
      native enzyme is composed of four homologous subunits. The isoelectric point of
      the enzyme was 4.9. The tryptophanase was stable to heating at 65 degrees C for
      20 min and the optimum temperature for the enzyme activity for 20 min reaction
      was 70 degrees C. The optimum pH was 7.0. The NH2-terminal amino acid sequence of
      this tryptophanase shows similarity to that of Escherichia coli K-12, despite a
      great difference in the thermostability of these two enzymes. The purified enzyme
      catalyzed the degradation (alpha, beta-elimination) of L-tryptophan into indole,
      pyruvate, and ammonia in the presence of pyridoxal-5'-phosphate. The Km value for
      L-tryptophan was 1.47 mM. 5-Hydroxy-L-tryptophan, 5-methyl-DL-tryptophan, L
      cysteine, S-methyl-L-cysteine, and L-serine were also used as substrates and
      converted to pyruvate. The reverse reaction of alpha, beta-elimination of this
      tryptophanase produced L-tryptophan from indole and pyruvate in the presence of a
      high concentration of ammonium acetate.

PMID- 1368767
TI  - Regioselective modification of Lysine's amino groups by proteases.
AB  - The regioselectivity of six serine proteases for the amino groups of lysine was
      investigated. alpha-Chymotrypsin showed a preference for the alpha-amino group,
      although the selectivity can be varied 10-fold depending on the reaction medium.
      Subtilisin Carlsberg and other bacterial proteases were highly specific for the
      epsilon-amino group, regardless of the reaction medium: they were used as
      catalysts for the preparative synthesis of isopeptides in anhydrous tert-amyl
      alcohol.

PMID- 1368768
TI  - Immobilization of Pseudomonas L-Phe oxidase on a nylon membrane for possible use
      as an amino acid sensor.

PMID- 1368769
TI  - NifA protein synthesized in vitro binds to the upstream activator sequence in the
      promoter of the Klebsiella oxytoca nifB gene.

PMID- 1368770
TI  - Nucleotide sequence of the bsr gene and N-terminal amino acid sequence of
      blasticidin S deaminase from blasticidin S resistant Escherichia coli TK121.

PMID- 1368771
TI  - Construction of an Escherichia coli export-affinity vector for expression and
      purification of foreign proteins by fusion to cyclomaltodextrin
      glucanotransferase.
AB  - A novel export-affinity fusion vector employing the gene encoding
      cyclomaltodextrin glucanotransferase (CGTase; cgt) from Bacillus circulans var.
      alkalophilus (ATCC 21783) is described. CGTase binds to various sugar polymers,
      which makes it simple to purify it to near homogeneity in a single step. The
      CGTase fusion protein vector was constructed by deleting the translational stop
      codons from the gene encoding CGTase (cgt) by in vitro mutagenesis. As models,
      genes encoding Escherichia coli alkaline phosphatase (APase; phoA) and Bacillus
      stearothermophilus (ATCC 12980) alpha-amylase (BStA; amy) were fused to cgt.
      Overexpression of wild type CGTase and the hybrid proteins under the control of
      the lac promoter caused a 'leaky phenotype' in E. coli, the outer membrane became
      permeable, which enabled the adsorption of the fusion proteins directly from the
      culture medium onto alpha-cyclodextrin (alpha-CD) coupled agarose. The hybrid
      proteins were eluted from the column with alpha-CD solution under mild conditions
      at pH 7.5. The CGTase-APase' fusion had a good in vivo stability, whereas the
      CGTase-BStA' was less stable. In the latter case, according to protein
      sequencing, the proteolytically sensitive site was on the BStA' side of the
      fusion. The C-terminus of CGTase was stable against proteolysis as shown by
      narrow pH range isoelectric focusing. The fused enzymes retained their biological
      activities.

PMID- 1368773
TI  - The use of multifunctional adsorbents to purify membrane-bound phosphatases from
      Zymomonas mobilis. Purification of acid phosphatase, alkaline phosphatase and
      ATPase.
AB  - The purification of detergent-solubilized membrane-bound phosphatases from
      Zymomonas mobilis using novel adsorbents is described. The prepared adsorbents
      have a hydrophobic core with functional groups attached. These functional groups
      may either increase or decrease the hydrophobicity of the adsorbent, or
      participate in other forms of interactions. Adsorption of acid phosphatase (ACP),
      alkaline phosphatase (ALP) and ATPase to these adsorbents was salt-promoted.
      Desorption was achieved by decreasing the salt concentration or by displacement
      with increasing concentration of Triton X-100. The results indicate that
      chromatography on multifunctional adsorbents that are predominantly hydrophobic
      in character is a procedure that can have a general applicability in purification
      of membrane proteins.

PMID- 1368772
TI  - Production of cyclomaltodextrin glucanotransferase of Bacillus circulans var.
      alkalophilus ATCC21783 in B. subtilis.
AB  - The cyclomaltodextrin glucanotransferase (CGTase, E.C. 2.4.1.19) gene from an
      alkalophilic Bacillus circulans var. alkalophilus ATCC21783 was cloned into
      Escherichia coli and B. subtilis. When cloned from E. coli to B. subtilis, the
      entire insert containing the CGTase gene was, depending on the plasmid
      construction, either unstable or the recombinant B. subtilis did not secrete the
      enzyme in significant amounts. To achieve efficient enzyme production in B.
      subtilis, the gene was placed under the control of the B. amyloliquefaciens alpha
      amylase promoter. In one of the constructions, both the promoter and the signal
      sequence of the gene were replaced with those of B. amyloliquefaciens, whereas in
      another construction only the promoter area was exchanged. The recombinant B.
      subtilis clones transformed with these plasmid constructions secreted CGTase into
      the culture medium 14 times as much as did the parental strain in shake flask
      cultures. In fermentor cultures in an industrially feasible medium the enzyme
      production was substantially higher, yielding 1.2 g/l of CGTase, which is about
      33 times the amount of the enzyme produced by the parental strain in
      corresponding fermentations. Both of the plasmid constructions were stable when
      grown over 50 generations without antibiotic selection.

PMID- 1368774
TI  - Serum-inducible gene expression in fibroblasts.
AB  - The proliferation of normal mammalian cells is regulated by external growth
      factors. The complex array of biochemical events triggered by these factors is
      believed to be modulated by changes in gene expression and leads to cell growth.
      The long range goals of this research are to identify, isolate, and characterize
      the genes that modulate cell growth and to determine the functions of their
      protein products. Previously, several genes were identified whose expression was
      characterized as growth-regulated; their cognate cytoplasmic transcripts were
      induced when quiescent cells were stimulated with serum. Predicated on the fact
      that only 1% of active genes respond to mitogenic stimulation, we hypothesize
      that these growth-regulated genes are functionally involved in the mitogenic
      process. We have identified one of these growth regulated genes by sequence
      analysis to be annexin II, a major substrate of tyrosine kinases. We have
      determined that the expression of this gene is growth-regulated and that its
      membrane/cytoskeleton association changes as a function of mitogenic stimulation.

PMID- 1368775
TI  - High resolution removal of virus from protein solutions using a membrane of
      unique structure.
AB  - We describe a new class of membrane that has the capability of removing particles
      such as viruses from solution with resolution and reproducibility superior to
      that of conventional membranes. This composite membrane is composed of a pre
      formed microporous membrane plus a thin asymmetric, finely porous retentive layer
      that is quite different from conventional ultrafilters. The protein sieving
      characteristics of this membrane are nearly equivalent to, but slightly less
      than, that of conventional 100,000 Dalton cut-off ultrafiltration membranes. This
      membrane uniquely shows particle retention characteristics that increase
      monotonically from 3 to 8 logs as a function of particle diameter in the range of
      28 to 93 nm. The performance of this membrane in both a single stage and a two
      stage system show that 4 to 6 log overall removal of virus particles in the size
      range 30 to 70 nm is possible with simultaneous high recovery of product protein.
      Clearance factors exceeding 6 logs are possible with viruses larger than 78 nm.
      In addition, the performance of process systems containing this membrane is
      predictable in accordance with the general membrane properties and equilibrium
      mass balance models. This membrane system is fully validatable and can be used in
      conjunction with other validated operations in a down-stream process to reliably
      achieve an over-all reduction of 12 logs of known or putative virus particles.

PMID- 1368778
TI  - Chemiluminescence in life science research. A new light on the subject.

PMID- 1368776
TI  - Lysozyme expression in Lactococcus lactis.
AB  - Three lysozyme-encoding genes, one of eukaryotic and two of prokaryotic origin,
      were expressed in Lactococcus lactis subsp. lactis. Hen egg white lysozyme (HEL)
      could be detected in L. lactis lysates by Western blotting. No lysozyme activity
      was observed, however, presumably because of the absence of correctly formed
      disulphide bonds in the L. lactis product. The functionally related lysozymes of
      the E. coli bacteriophages T4 and lambda were produced as biologically active
      proteins in L. lactis. In both cases, the highest expression levels were obtained
      using configurations in which the bacteriophage lysozyme genes had been
      translationally coupled to a short open reading frame of lactococcal origin. Both
      enzymes, like HEL, may prevent the growth of food-spoilage bacteria.

PMID- 1368777
TI  - Cloning of the alpha-amylase cDNA of Aspergillus shirousamii and its expression
      in Saccharomyces cerevisiae.
AB  - alpha-Amylase cDNA was cloned and sequenced from Aspergillus shirousamii RIB2504.
      The putative protein deduced from the cDNA open reading frame (ORF) consisted of
      499 amino acids with a molecular weight of 55,000. The amino acid sequence was
      identical to that of the ORF of the Taka-amylase A gene of Aspergillus oryzae,
      while the nucleotide sequence was different at two and six positions in the cDNA
      ORF and 3' non-coding regions, respectively, so far determined. The alpha-amylase
      cDNA was expressed in Saccharomyces cerevisiae under the control of the yeast
      ADH1 promoter using a YEp-type plasmid, pYcDE1. The cDNA of glucoamylase, which
      was previously cloned from the same organism, was also expressed under the same
      conditions. Consequently, active alpha-amylase and glucoamylase were efficiently
      secreted into the culture medium. The amino acid sequence of the N-terminal
      regions of these enzymes purified from the yeast culture medium confirmed that
      the signal sequences of these enzymes were cleaved off at the same positions as
      those of the native enzymes of A. shirousamii.

PMID- 1368779
TI  - Apolipoproteins as markers for coronary heart disease.

PMID- 1368780
TI  - A PC-based monitoring and alarm system.

PMID- 1368781
TI  - Rapid isolation of plasmid DNA.

PMID- 1368782
TI  - Dialysis and ultrafiltration: estimating quantitative separations.

PMID- 1368783
TI  - Rapid and reliable DNA sequencing with a dideoxy sequencing kit.

PMID- 1368784
TI  - Cloning of a probe for a previously undescribed enterobacterial tetracycline
      resistance gene.
AB  - An 8.35 kb BamHI fragment was cloned from the plasmid R714a. It encoded
      resistances to chloramphenicol, streptomycin, spectinomycin and tetracycline.
      Tetracycline resistance was determined by a locus without homology to the known
      enterobacterial gene classes, TetA-TetE. Further subcloning of the fragment
      located an unusual tetracycline resistance gene on a 4.7 kb BamHI-BglII fragment.
      A physical-genetic map of this fragment indicated that the gene was bisected by a
      PstI site. Deletion analysis and insertion mutagenesis were used to define a
      suitable probe. An intragenic PstI-AvaI fragment of 1.2 kb was identified, and
      used as a non-radioactive probe, being specific for this previously undescribed
      enterobacterial Tet gene.

PMID- 1368785
TI  - Fungistatic and fungicidal effects of the ionophores monensin and tetronasin on
      the rumen fungus Neocallimastix sp. LM1.
AB  - The ionophore antibiotics monensin and tetronasin have been reported to inhibit
      anaerobic fungi in vitro, and are suitable for animal use. In this study, their
      effectiveness in removing the anaerobic fungus Neocallimastix sp. LM1 from the
      rumen was investigated in vitro. Both antibiotics were fungistatic: tetronasin at
      0.5 microgram/ml and monensin at 1.0 microgram/ml; exposure for 24 h did not
      inhibit subsequent growth after removal of the ionophore. The ionophores were
      fungicidal at much higher concentrations, 1 microgram/ml for tetronasin and 16
      micrograms/ml for monensin. It seems likely that the combination of relatively
      high inhibitory dose and the fungistatic nature of monensin would explain
      difficulties in using this compound to eliminate anaerobic fungi from the rumens
      of experimental animals.

PMID- 1368786
TI  - High frequency of independent IS50 transposition during Tn5 mutagenesis of
      Bordetella pertussis virulence-associated genes.
AB  - Transposon Tn5-generated mutants of Bordetella pertussis were selected on the
      basis of their inability to bind the dye Congo red (Crb-). No mutants which were
      solely Crb- were found. Ten mutants were phenotypically equivalent to previously
      described strains with mutations in the virulence regulatory (bvg) locus and
      failed to express a range of virulence-associated factors. Two of these mutants
      were shown to have Tn5 insertions within the bvg locus, while another two mutants
      showed deletions in this regulatory region. Complementation studies indicated
      that the other six mutants had spontaneous mutations in the bvg locus, but with
      Tn5 inserted elsewhere in the chromosome. Several of the mutants, besides having
      a single Tn5 insertion, also showed additional IS50 insertions, indicating that
      the IS50 element contained within Tn5 had transposed independently. Such
      additional insertion events, which themselves would have the potential to cause
      mutation, could complicate the interpretation of mutant phenotypes which could
      thus arise from the insertional inactivation of more than one gene.

PMID- 1368787
TI  - Plasmid-encoded resistance to tetracycline in Staphylococcus haemolyticus.
AB  - A small 4.35 kb plasmid, designated pSTS4, was isolated from a multiresistant
      Staphylococcus haemolyticus culture. It conferred resistance to tetracycline as
      shown by protoplast transformation. pSTS4 was further characterized by
      restriction endonuclease analyses and a preliminary restriction map constructed.
      It shared some structural similarities with previously described small TcR
      plasmids from other staphylococcal species of human and animal origin. pSTS4
      encoded two proteins of approximately 37 kDa and 52 kDa as revealed by combined
      in vitro transcription/translation assays.

PMID- 1368788
TI  - Controlling chirality in enzymatic synthesis.

PMID- 1368789
TI  - New horizons for stem-cell bioreactors.

PMID- 1368790
TI  - Europe's emerging biopharmaceutical companies.

PMID- 1368791
TI  - Characterization of RNA-mediated resistance to tomato spotted wilt virus in
      transgenic tobacco plants.
AB  - Recently high levels of protection against tomato spotted wilt virus (TSWV), a
      negative-strand RNA virus infecting plants, have been obtained by transforming
      tobacco with viral nucleoprotein (N) gene sequences. Here we demonstrate that
      this protection is primarily due to the presence of N gene transcripts in the
      cells of transgenic plants, and hence appears to be RNA-mediated. Further,
      transgenic tobacco plants are only protected to isolates and strains of TSWV and
      not to other tospoviruses that share considerable nucleotide sequence homology in
      their N genes to TSWV. In addition to being protected after mechanical
      inoculation, the transgenic tobacco plants are also resistant to inoculation
      using viruliferous thrips, i.e. Frankliniella occidentalis (Perg.), one of the
      most important natural vector species.

PMID- 1368792
TI  - High level expression of streptokinase in Escherichia coli.
AB  - Streptokinase (SK), which activates human plasminogen by promoting its conversion
      to plasmin, is normally obtained from beta-hemolytic streptococci. Treatment with
      SK is an effective therapy for improving survival and preserving left ventricular
      function after coronary thrombosis. We report the cloning, expression in E. coli
      to levels of 25% of the total cell protein, and characterization of a novel SK
      (SKC-2) gene, the product of which is functionally equivalent to the naturally
      derived protein. The availability of a recombinant streptokinase (rSK) in high
      yield and purity offers a potentially attractive alternative source of this
      important therapeutic agent.

PMID- 1368793
TI  - Effect of glycosylation on properties of soluble interferon gamma receptors
      produced in prokaryotic and eukaryotic expression systems.
AB  - We investigated the influence of glycosylation on solubility, chromatographic
      behavior and resistance to heat- and chaotrope-dependent denaturation and
      proteolytic digestion of three recombinant human interferon gamma receptors
      produced in Escherichia coli, Spodoptera frugiperda and Chinese hamster ovary
      cells. The proteins produced in the eukaryotic expression systems were
      glycosylated, carrying different, heterogeneous carbohydrate moieties. They were
      assayed fully glycosylated and after removal of the oligosaccharides. Although
      glycosylation influenced the chromatographic behavior of the tested proteins, it
      did not protect against proteolysis and heat- or chaotrope-induced denaturation.
      The glycosylated receptors were slightly more sensitive to certain proteolytic
      cleavages and slightly less resistant to chaotropes, than the soluble receptor
      produced in Escherichia coli.

PMID- 1368794
TI  - Baculovirus expression of alkaline phosphatase as a reporter gene for evaluation
      of production, glycosylation and secretion.
AB  - We have devised a simple and efficient baculovirus expression vector system to
      evaluate insect tissue culture cells for their capacity to express, glycosylate
      and secrete foreign proteins. A truncated placental alkaline phosphatase (SEAP)
      gene was inserted into the Autographa californica nuclear polyhedrosis virus
      (AcMNPV) genome under the transcriptional control of the polyhedrin gene
      promoter. Production levels, glycosylation, and secretion of the recombinant
      protein were examined in Trichoplusia ni (BTI-TN-5B1-4) and Spodoptera frugiperda
      (Sf9) cell lines. The assay for SEAP activity, which is fast, inexpensive, and
      quantitative to concentrations of 20 picograms per milliliter, was used to assess
      cell-associated and secreted SEAP activity. The proportion of SEAP which is
      modified with N-linked oligosaccharide can also be determined due to the
      difference in mobilities during SDS-PAGE between the glycosylated and
      nonglycosylated forms of the protein.

PMID- 1368795
TI  - Non-neutralizing monoclonal antibodies against Ras GTPase-activating protein:
      production, characterization and use in an enzyme immunometric assay.
AB  - We studied several monoclonal antibodies (mAbs) raised against the 100 kD Ras
      GTPase activating protein (p100-GAP), which was purified from human placenta.
      These antibodies recognized p120-GAP and p100-GAP in native and in denatured
      forms. The most reactive, GP15 and GP200, both recognized distinct epitopes and
      did not neutralize GTPase stimulatory activity. These two mAbs were selected for
      a two-site enzyme immunoassay, using covalent conjugates of the antibodies
      coupled to the tetrameric form of acetylcholinesterase as tracer. This assay was
      used to quantify Ras-GAP in both normal and tumor tissues and cell extracts.

PMID- 1368796
TI  - Kinetics and mechanisms of reactions catalysed by immobilized lipases.
AB  - This review focuses on the kinetics and mechanisms of reactions catalysed by
      immobilized lipases. The effects of pH, temperature, and various substances on
      the catalytic properties of immobilized lipases and on the processes by which
      they are deactivated are reviewed and discussed.

PMID- 1368798
TI  - Electrochemical bioreactor with regeneration of NAD+ by rotating graphite disk
      electrode with PMS adsorbed.
AB  - Kinetic constants were compared among p-quinone, 2,6-dichlorophenolindophenol,
      phenazine methosulfate (PMS), methylene blue, and FAD in the oxidation of NADH.
      Among those, PMS was selected for its highest rate constant as a mediator for the
      electrochemical oxidation of NAD. The PMS could be stably immobilized on a
      graphite electrode surface by adsorption. The PMS adsorbed and that in the
      solution showed distinctly separated peaks in the cyclic voltammogram. The
      immobilized PMS functioned as an immobilized mediator to reduce the overpotential
      in the electrochemical oxidation of NAD so that the electrode could be used as an
      NAD regenerator. For the construction of an electrochemical bioreactor, a
      specially designed rotating disk graphite electrode was used. In spite of its
      extraordinarily large surface area, the behavior of the rotating disc electrode
      was described well by the Levich law. The NAD oxidation system of the rotating
      graphite disk electrode with PMS adsorbed was combined with glucose-6-phosphate
      dehydrogenase reaction, which reduced NAD with the consumption of glucose-6
      phosphate. The electrochemical bioreactor system worked well with recycling of
      NAD at a high current efficiency.

PMID- 1368797
TI  - Relationship between hybridoma growth and monoclonal antibody production.
AB  - Factors affecting cell growth and antibody production in a mouse hybridoma were
      investigated. Antibody was produced during the growth and decline phases of a
      batch culture with an increase in the specific rate of antibody production during
      the decline phase. The specific rate of antibody production was also increased in
      cells arrested by 2 mM thymidine, suggesting that cell proliferation and antibody
      production can be uncoupled. Reduced serum concentrations resulted in lower cell
      growth rates but increased antibody production rates. However, this trend was
      reversed in hybridomas which had been arrested by thymidine, since the highest
      antibody production rate was associated with high serum concentrations. Likewise,
      in proliferating cells, the optimum pH for antibody production (pH 6.8) was lower
      than the optimum pH for cell growth (pH 7.2), whereas in thymidine-blocked cells,
      the highest antibody production rate was at pH 7.2. High antibody production
      rates and product yields were also associated with low growth rates in continuous
      cultures. The possibility that antibody was under cell cycle control was
      investigated in synchronized hybridoma cultures. Antibody production occurred
      during G1 and G2 with a decline in the M phase and evidence of a further decline
      in the S phase. Thus antibody production was not restricted to the G1 and S phase
      in this hybridoma.

PMID- 1368799
TI  - Additional stabilization of penicillin G acylase-agarose derivatives by
      controlled chemical modification with formaldehyde.
AB  - We have tested the effect of chemical modifications with formaldehyde on the
      activity/stability of immobilized derivatives of the enzyme penicillin G acylase
      (PGA). These derivatives were previously stabilized through enzyme-support
      multipoint covalent attachment. We carried out very different chemical treatments
      of our derivatives by testing the effect of different variables which control the
      intensity and the nature of these amine-formaldehyde reactions. The variables
      tested were: formaldehyde concentration, pH, time, and temperature. We also
      developed a colorimetric titration of the free amine groups on immobilized PGA in
      order to evaluate the extension of the reaction between formaldehyde and the
      amine groups of the enzyme. As a consequence of these studies, we have been able
      to get additional stabilizations of our previously stabilized-immobilized
      derivatives: e.g. a factor of 24-fold was achieved in terms of stabilization
      against irreversible thermal inactivation. The integrated effect of additional
      chemical modification plus previous multipoint covalent attachment has allowed us
      to prepare PGA derivatives which are 50,000 more thermostable than native PGA as
      well as most of the commercial PGA derivatives.

PMID- 1368800
TI  - Penicillin amidase-catalysed transfer of low specific acyl moiety. Synthesis of 7
      benzoxazolonylacetamido desacetoxycephalosporanic acid.
AB  - The methyl ester of 2-benzoxazolon-3-yl-acetic acid was used as an acyl donor in
      the penicillin amidase-catalysed transfer reaction to 7
      aminodesacetoxycephalosporanic acid. The synthesis of 7-(2-benzoxazolon-3-yl
      acetamido)-desacetoxycephalosporanic acid was carried out as a kinetically
      controlled reaction. A characteristic feature of this system is that the
      benzoxazolone derivatives are very low specific substrates for penicillin amidase
      (the kcat/Km values for their hydrolysis were shown to be 10(5)-fold lower
      compared to the corresponding values for phenylacetyl derivatives). Nevertheless,
      penicillin amidase proved to be an effective catalyst for the synthesis of these
      new cephem derivatives (50% yield for 6 h). The reason is the observed unusually
      high value for the transferase-hydrolase activity ratio. The determined value for
      (k3'/k3)app = 120,000 implies that in this case of low specific acyl moiety,
      penicillin amidase acts more like a transferase than a hydrolase. The maximum
      yield has been increased up to 70% by lowering the reaction temperature and
      stepwise feeding of the reaction medium with the acyl component. The results
      obtained extend the potential of the penicillin amidase as a catalyst for the
      synthesis of a new group of biologically active cephem derivatives.

PMID- 1368801
TI  - Production of an enzymatic active protein using a continuous flow cell-free
      translation system.
AB  - We have examined the characteristics of protein synthesis in an improved
      continuous flow cell-free translation system prepared from wheat germ extract
      with dihydrofolate reductase (dhfr) mRNA as the translated message. Continuous
      buffer flow and separation of product from the reaction mixture were accomplished
      by the use of a modified Amicon ultrafiltration chamber as reaction vessel. The
      system produced protein for more than 20 h, and the product had an activity of
      dhfr comparable to that of authentic enzyme from E. coli. Analysis of RNA
      recovered from the filtrate supports the notion that a functionally active
      protein-synthesizing machinery is superorganized in a dynamic complex.

PMID- 1368802
TI  - Lactate dehydrogenase (LDH) activity of the cultured eukaryotic cells as marker
      of the number of dead cells in the medium [corrected].
AB  - One significant problem in monitoring a culture's evolution is to assess change
      in cell viability. We have demonstrated that LDH release could be a good
      indicator of cellular damage of many cell lines, especially during shear stress
      or sonication. Moreover, we have found a significant correlation between the
      number of dead cells, determined by Trypan Blue staining, and LDH activity
      measurements in the supernatant of hybridoma strains, whatever the culture
      conditions. We have also shown that when viability is still near 100% no LDH is
      released even at high cell concentrations. Therefore, LDH should serve as a
      potential marker of cell injury and death.

PMID- 1368804
TI  - Fusions to the 5' end of a gene encoding a two-domain analogue of staphylococcal
      protein A.
AB  - A novel gene fusion system has been constructed for fusions to the 5' end of gene
      zz, encoding a two-domain analogue of staphylococcal protein A designated ZZ.
      Four different genes were fused to the 5' end of zz, and their gene products were
      analyzed. One of the genes encodes a protein located intracellularly in
      Escherichia coli and the other three genes encode gene products destined for
      secretion across the cytoplasmic membrane by the presence of an amino terminal
      signal sequence. After production in E. coli, the fusion proteins were purified
      in a single step by IgG-affinity chromatography. The purified ZZ fusions could be
      used directly for amino terminal sequencing to confirm the start of translation
      of the intracellular product and the processing of the signal peptide of the
      translocated products. This is the first example of ZZ fusions to the C-terminus
      of gene products. To simplify the general use of fusions to the 5' end of zz, a
      new plasmid vector was constructed containing a multi restriction enzyme cloning
      linker and the lacZ' gene which enables screening for production in alpha
      complementing supE strains of E. coli on indicator plates.

PMID- 1368803
TI  - Influence of medium composition on penicillin V production in a stirred tank
      reactor.
AB  - Penicillin production with a high-producing strain Penicillium chrysogenum was
      investigated under well-controlled conditions in a stirred tank reactor with
      complex media containing lard oil and lactose on the one hand, and lactose on the
      other hand. With lard oil, cell growth and product formation rates were higher,
      and the production time was shorter by 40 h than without lard oil. On account of
      the longer production time without lard oil, the amount of beta-lactam compounds
      was higher (29.93 g l-1), but the mole fraction of the decomposed products
      (penicilloic acid and penilloic acid) was larger (0.282) than the amount of
      penicillin V (23.25 g l-1) and the decomposed mole fraction (0.0747) with lard
      oil. The final product concentrations were about the same (20.86 g l-1 or 35,462
      IU ml-1 with lard oil, and 20.43 g l-1 or 34510 IU ml-1 without lard oil). The
      mole fractions of the by-product (p-OH-penicillin V) were 0.0365 and 0.066. The
      substitution of lard oil with lactose is possible without a considerable
      reduction of process performance.

PMID- 1368805
TI  - Foaming and media surfactant effects on the cultivation of animal cells in
      stirred and sparged bioreactors.
AB  - Foam formation and the subsequent cell damage/losses in the foam layer were found
      to be the major problems affecting cell growth and monoclonal antibody (MAb)
      production in stirred and sparged bioreactors for both serum-supplemented and
      serum-free media. Surfactants in the culture media had a profound effect on cell
      growth by changing both the properties of bubbles and the qualities of foam
      formed. Comparable cell growth and MAb production in sparged bioreactors and in
      stirred and surface-aerated control cultures were observed only in Pluronic F-68
      containing culture media. In media devoid of Pluronic F-68, cells became more
      sensitive to direct bubble aeration in the presence of antifoam agent which was
      used to suppress foam formation. Compared with serum-supplemented medium, more
      severe cell damage effects were observed in serum-free medium. In addition, serum
      free medium devoid of cells was partially degraded under continuous air sparging.
      The mechanism of this damage effect was not clear. Pluronic F-68 provided
      protective effect to cells but not to the medium. A theoretical model based on
      the surface active properties of Pluronic F-68 was proposed to account for its
      protective effect on cell growth. Optimum media surfactant composition in terms
      of maximum cell growth and minimum foam formation was proposed for stirred and
      sparged animal cell bioreactor.

PMID- 1368806
TI  - Purification of recombinant human growth hormone by isoelectric focusing in a
      multicompartment electrolyzer with Immobiline membranes.
AB  - Recombinant human growth hormone (r-hGH) expressed in Escherichia coli, was 70
      80% purified by a combination of ion-exchange chromatography and metal ion
      affinity chromatography. For the last purification step, a multicompartment
      electrolyzer was used, containing three compartments delimited by isoelectric
      membranes and two additional anodic and cathodic chambers. The central
      compartment was situated between two membranes having isoelectric points (pI) of
      5.08 (anodic) and of 5.16 (cathodic), i.e. equidistant from the pI value of hGH
      (pI 5.12). r-hGH was isoelectric between these two membranes and could not leave
      the central chamber, while more acidic and more cathodic impurities collected in
      the two lateral chambers under the influence of the electric field. The r-hGH,
      thus purified, exhibited a single band by isoelectric focusing (IEF) in
      immobilized pH gradients (IPG) and gave recoveries greater than 90%. The problem
      of isoelectric precipitation in a practically ion-free environment was alleviated
      by focusing in 30% glycerol added with 1% neutral detergent (Nonidet-P40). The
      latter was eliminated by passage through a Q-Sepharose column after collecting
      the pI 5.12 band from the electrolyzer. Also the pre-hormone (pre-hGH) can be
      purified in a similar manner (30% glycerol, 1% Nonidet P-40) between two
      membranes having pIs 4.77 (anodic) and 4.87 (cathodic) (pre-hGH pI 4.82). This
      paper demonstrates the possibility of purifying by a focusing process also poorly
      soluble proteins at the pI.

PMID- 1368808
TI  - Reactor modelling for electrochemical processes.
AB  - This paper presents a relatively straightforward approach to the modelling of
      electrochemical reactors operated in batch or continuous modes. The models are
      based on ideal flow assumptions of either well-mixed or plug flow and incorporate
      reaction rate models based on electrochemical kinetics and mass transport at one
      electrode. General characteristics of the reactor models are described,
      particularly with regard to the need for good mass transport in metal recovery
      applications. An example is given on the use of the model in the recovery of a
      heavy metal (Cd2+) from an acidified solution containing Cd(II) and Fe(III) ions.
      The reaction rate model is based on experimental data.

PMID- 1368807
TI  - Stabilization of NAD(+)-dependent dehydrogenases and diaphorase by bilayer
      encagement.
AB  - A feasibility study aimed at stabilization of L-lactate-dehydrogenase, L-malate
      dehydrogenase, alcohol-dehydrogenase and diaphorase by the recently described
      method of enzyme 'encagement' was conducted. This method involves derivatizing
      the enzymes with polyglutaraldehyde, followed by secondary crosslinking with
      amino derivatives of polyacrylamide. Encagement conditions were optimized for
      each of the four enzymes, so as to achieve the highest thermal stability combined
      with highest catalytic activity. Depending on the encagement conditions, residual
      activities were in the range of 18% to 96% with higher values in the presence of
      cofactors. Increases in thermal stabilization of up to 26-fold were obtained. For
      high retention of enzymic activity and stability, the most significant factor was
      the concentration of polyglutaraldehyde; the crosslinking polymers had only a
      negligible effect. Furthermore, the significant enhancement in thermal stability
      could be attained without perturbing the kinetic parameters: Km values for NADH
      and pH optima remained unaltered for the stabilized enzymes.

PMID- 1368809
TI  - Fumaric acid production from hydrolysates of starch-based substrates.
AB  - Fumaric acid production by Rhizopus arrhizus from commercial hydrolysates of corn
      starch (i.e. glucose molasses) was studied at different initial concentrations of
      glucose (S) and C:N ratios (R) by performing a 3(2) factorial experiment. By
      using the response surface methodology and statistical analysis, fumaric acid
      (YF) and mycelial biomass (YX) yields, as referred to the initial concentration
      of glucose and fumaric acid productivity (PF), were fitted to the only
      significant first-order effects of S and R with mean percentage errors ranging
      from 11 to 15%. The resulting empiric models were used to determine the optimal
      values of S (100-130 g dm-3) and R (150-210 g-atom C per g-atom N) associated
      with YF and PF varying in the ranges 40-49% and 7-8.5 g dm-3 day-1, respectively.
      After establishing the validity of these data at the 95% confidence level, an
      optimal operating condition (S = 120 g dm-3 and R = 150) was further tested using
      other substrates (i.e. glucose and acid or enzymatic hydrolysates of cassava,
      corn and potato flours). Statistically significant improvements in the fumaric
      acid yield and productivity were determined with respect to the predicted values.
      Since the highest values of YF and PF were obtained from the acid hydrolysates of
      the starch-based materials and such values were also found to be insensitive to
      the substrate used (at a probability level of 0.05), the above operating
      condition might be further employed to minimise fumaric acid production costs as
      a function of the feedstock used.

PMID- 1368811
TI  - Growth stimulating activity of heat shock protein 90 alpha to lymphoid cell lines
      in serum-free medium.
AB  - A growth stimulating factor was purified from the culture supernatant of human
      human hybridoma SH-76 cells in serum-free RPMI 1640 medium by the serial use of
      DEAE anion and heparin affinity chromatographies. The factor was a 85 kDa protein
      on SDS-polyacrylamide gel electrophoresis. N-terminal amino acid sequence
      (PEETQTQDQPME) of the protein was coincident with that of heat shock protein 90
      alpha (HSP90 alpha). The protein reacted with anti-HSP90 monoclonal antibody.
      These results suggest that the protein was a member of HSP90 alpha family after
      taking other circumstantial evidence into account. The protein stimulated the
      growth of some lymphoid cell lines such as human B-lymphoblastoid cell line HO
      323-3 hybridomas derived from HO-323, and several other lymphoid cell lines.
      There were several lymphoid cell lines which did not respond to the protein.
      Growth stimulating activity of the protein was heat-unstable and significantly
      decreased at above 60 degrees C. These are the first data that describe growth
      stimulating activity of heat shock protein 90 alpha.

PMID- 1368810
TI  - High level expression of a frog alpha-amidating enzyme, AE-II, in cultured cells
      and silkworm larvae using a Bombyx mori nuclear polyhedrosis virus expression
      vector.
AB  - A Xenopus laevis peptidyl C-terminal alpha-amidating enzyme (AE-II) gene,
      modified by deletion of a region encoding the putative membrane-spanning domain
      and the putative C-terminal cytosolic tail, was expressed in BoMo-15 AIIc insect
      cells and silkworm larvae using a Bombyx mori baculovirus expression vector
      system. The expressed enzyme was identified predominantly in the culture medium
      and the hemolymph of silkworm larvae, indicating successful secretion of the
      expressed AE-II. The level of recombinant enzyme in the larval hemolymph at 4
      days post-infection (40 micrograms/ml) was more than 100-fold the peak levels
      found in the culture medium (250 ng/ml). The enzyme activity in the larval
      hemolymph at 4 days post-infection was 3700 units/ml.

PMID- 1368812
TI  - Two-dimensional electrophoresis as a tool for control of quality and consistency
      in production systems using animal cells. Two-dimensional electrophoresis in
      animal cell culture technology.
AB  - A nonrecombinant human melanoma cell line and recombinant chinese hamster ovary
      (CHO) cells were used as examples for long-term in vitro cultivation in protein
      free media. The method used to monitor the consistency of protein release by
      these mammalian cells was two-dimensional electrophoresis with immobilized pH
      gradient. Secreted proteins from a melanoma cell line cultivated in a continuous
      fermentation system over a period of 22 months were monitored. Two-dimensional
      patterns of secreted proteins were compared and the stability of their
      composition was determined over a period of nearly 14 months, with significant
      pattern variation being observed after 14 months. The protein pattern from this
      extended in vitro culture was compared to those of the very same melanoma cell
      line recultivated after being frozen in liquid nitrogen for more than 2 years.
      Due to the high resolution of complex polypeptide mixtures and the possibility to
      detect even minor differences in the composition of protein patterns, we propose
      the two-dimensional electrophoresis as a tool for quality assessment in animal
      cell culture technology.

PMID- 1368814
TI  - A comparison of simple growth vessels and a specially designed bioreactor for the
      cultivation of hybridoma cells.
AB  - Three tank type bioreactors of very simple design were compared to a commercially
      available laboratory-scale bioreactor, designed especially for mammalian cell
      culture, for their ability to support hybridoma growth and antibody production
      under batch culture conditions. The comparison reveals quite similar numbers for
      maximum viable cell densities and IgG production, despite large differences in
      vessel and agitator geometry and aeration mode. Furthermore, some data indicate
      that the hydrodynamic stress level in the growth vessels may influence the
      specific production rate of the cells and thus the overall productivity of the
      reactors.

PMID- 1368815
TI  - Transferrin recycling perfusion culture of hybridoma cells.
AB  - A perfusion culture of hybridoma cells in serum-free medium recycling transferrin
      was carried out, which greatly reduced the level of transferrin that was needed.
      The culture was maintained even without supplying transferrin for nine days. IgG
      concentration reached 1.1 mg ml-1 in a month of recycling and its ratio to the
      total protein was 45.8%. The affinity of the antibody did not decrease and no
      degradation was observed after long recycling period. The cell density under
      recycling condition was 2-3 times higher than that without recycling. It was
      indicated that there was autocrine growth promoting activity in the culture
      supernatant.

PMID- 1368813
TI  - Cell culture systems and in vitro toxicity testing. Technical report no. 4 of the
      Johns Hopkins Center for Alternatives to Animal Testing (CAAT): technical
      workshop of June 13-15, 1990.

PMID- 1368816
TI  - An easy-to-handle semi-automated method for media development using a
      colorimetric viability assay and fractional factorial designs.
AB  - A rapid and effective semi-automated screening method has been developed for the
      development of growth media for mammalian cell culture. The method has proven to
      be a powerful tool for preliminary evaluation and comparison of new media
      formulations, but has some inherent disadvantages, which are important to
      recognise in order to interpret the results.

PMID- 1368817
TI  - Determination of division rates of rCHO cells in high density and immobilized
      fermentation systems by flow cytometry.
AB  - As most high density and immobilized fermentation systems do not allow the direct
      quantitative determination of cell density, two flow cytometric methods (the
      determination of incorporation of bromodeoxyuridine into newly synthesized DNA
      and the increase in mitotic cells by colchicine blockage) were evaluated as to
      their suitability to measure true division rates of cells in bioreactors. The
      BrdU method gave division rates identical to the growth rates measured by cell
      count, while the colchicine block method gave values that were lower and varied
      with the cell line. This is due to the cytotoxicity of colchicine and makes a
      calibration of the method for each cell line necessary. Both methods have been
      successfully used to measure division rates of rCHO cells immobilized in an
      alginate matrix as well as in macroporous carriers in a fluidised bed system and
      in dialysis culture.

PMID- 1368818
TI  - Evaluation of the physiological value of porcine luteal cells isolated in various
      stages of the luteal phase: tissue culture approach.
AB  - Porcine luteal cells were collected from corpora lutea in four different stages
      of the luteal phase and cultured as monolayers. Progesterone (P4) secretion was
      assayed using radioimmunoassays (Gregoraszczuk, 1991). Luteal cells cultured from
      porcine corpora lutea collected in the early luteal phase maintained
      steroidogenic capacity for 6 days in culture until the time comparable with
      midluteal corpora lutea. Luteal cells collected from mature and regressing
      corpora lutea did not dedifferentiate during 2 days of culture. After this time
      secretion of progesterone decreased to undetectable amounts characteristic of old
      corpora lutea. The regression in the culture progressed. The results demonstrate
      that the degree of the decline of progesterone depends on the type of corpus
      luteum, which is connected to particular time intervals of the luteal phase.
      Before starting experiments it is necessary to take into consideration the stage
      of the luteal phase from which the material is collected for culture. This study
      provides evidence that long term culture is useful for investigating a variety of
      aspects of luteal function only if cells are collected in the early luteal phase.
      Short term culture is suitable for investigation of cells collected from mid and
      late luteal phase. Regulation of luteal function is dependent on stage of the
      luteal phase.

PMID- 1368820
TI  - Accuracy of the endpoint assay for virus titration.
AB  - The statistics of estimators used with the endpoint assay for virus titration
      were investigated. For a standard assay with 10 wells/dilution, the graphical
      estimator traditionally used was found to produce estimates with significant
      positive bias and a relatively low accuracy. Furthermore, the graphical estimator
      was found to be inconsistent. A superior estimator based on the maximum
      likelihood principle was developed. The results are discussed in relation to the
      choice between the endpoint titration assay and the plaque assay, and an
      alternative two-stage assay is presented.

PMID- 1368819
TI  - A novel protease obtained from FBS-containing culture supernatant, that processes
      single chain form hepatocyte growth factor to two chain form in serum-free
      culture.
AB  - The recombinant human hepatocyte growth factor (r-hHGF) produced by Chinese
      hamster ovary cells transfected with hHGF cDNA (CHO BD-24 cells) was the two
      chain form in fetal bovine serum (FBS) containing culture. However, in serum-free
      culture the non-processed r-hHGF, single chain form, was detected with two chain
      form r-hHGF. We purified the protease that proteolytically processed single chain
      r-hHGF to two chain form r-hHGF. A protease was purified to give a single peak
      from the culture supernatant by use of several column chromatographies. When this
      protease was added to serum-free culture of CHO BD-24 cells, the proteolytic
      processing of single chain r-hHGF to two chain form r-hHGF was completely
      achieved. This protease was found to be composed of two peptide chains with
      molecular mass of 38 kDa under non-reducing condition by SDS-PAGE. The results of
      N-terminal amino acid sequence analysis and inhibitor selectivity suggested that
      this protease was a novel serine protease originating from fetal bovine serum.

PMID- 1368821
TI  - Formation of bridges and large cellular clumps in CHO-cell microcarrier cultures:
      effects of agitation, dimethyl sulfoxide and calf serum.
AB  - We have investigated conditions that inhibit the tendency of CHO K1 cells to form
      cellular bridges between microcarriers and dense clumps of cellular overgrowth in
      microcarrier cultures. Microcarrier aggregation by cellular bridge formation was
      found to occur only during periods of rapid cell growth. The level of
      microcarrier aggregation decreased with increasing agitation intensity. Dense
      masses of cellular overgrowth formed inside bridges connecting the microcarriers
      and in clumps that protruded off the microcarrier surface. To replace cells that
      were continuously sheared from the microcarriers, cell growth occurred
      preferentially in areas of overgrowth after confluent microcarriers were
      maintained in a serum-free medium. This ultimately led to poor surface coverage
      as bare spots developed on the microcarrier away from the areas of dense cellular
      overgrowth. The development of bare spots was inhibited when confluent
      microcarriers were maintained in medium supplemented with 1% serum. The
      development of cellular overgrowth was inhibited by dimethyl sulfoxide. Thus,
      maintaining confluent microcarriers in medium supplemented with 1% dimethyl
      sulfoxide and 1% calf serum resulted in microcarriers that appeared similar to
      monolayer cultures. There was also a decrease in bridging in cultures
      supplemented with either 1% calf serum or 1% dimethyl sulfoxide/1% calf serum
      compared to serum-free cultures.

PMID- 1368822
TI  - Long-term survival and production of testosterone by immobilized human embryonic
      testis fragments.
AB  - To study a new approach of graft preparation for transplantation of Leydig cells
      to correct androgen abnormality we have cultivated immobilized human embryonic
      testis fragments. The cultures were viable for at least 17 days and continuously
      produced testosterone. The paraffin sections showed histotypic organization of
      immobilized tissues, but not of free tissues, with good preservation of cells.
      This indicates that immobilized testicle fragments can be considered as
      candidates for transplantation grafts.

PMID- 1368823
TI  - Second International Symposium on the Biosafety Results of Genetically Modified
      Plants and Microorganisms. May 1992, Goslar, FRG.

PMID- 1368824
TI  - Comments on selected ecological aspects of "genetic manipulation: the threat or
      the glory".

PMID- 1368825
TI  - Syntheses of recombinant yellowtail and flounder growth hormones in Escherichia
      coli.
AB  - For syntheses of recombinant yellowtail and flounder growth hormones (r-yGH and r
      fGH) in E. coli, expression plasmids were constructed. The expression level of r
      yGH and r-fGH in the host cells were very high, reaching 15 and 8% of the total
      protein, respectively. These product proteins were accumulated in inclusion
      bodies in the cells. The recombinant hormones were isolated from the pellets ina
      glutathione reduction/oxidation buffer. The refolded hormones were further
      purified by DEAE-Toyopearl 650M chromatography to homogeneity. The purified r-yGH
      and r-fGH were composed of 188 and 174 amino acid residues, respectively, having
      amino-terminal sequences starting with methionine. The recombinant hormones had
      potent growth-promoting activities on juvenile rainbow trout Salmo gairdneri in a
      dose-dependent manner.

PMID- 1368826
TI  - In vivo biotinylation of fusion proteins expressed in Escherichia coli with a
      sequence of Propionibacterium freudenreichii transcarboxylase 1.3S biotin
      subunit.
AB  - Biotinylation of fusion proteins in E. coli was studied using a sequence of
      Propionibacterium freudenreichii transcarboxylase 1.3S biotin subunit. As the
      biotinylation sequence, we examined two sequences: one was of amino acid residues
      [84-123] of 1.3S, a partial sequence containing a region from a conserved
      tetrapeptide (Ala-Met-Bct-Met) around the biotinyl lysine (Bct) to the carboxyl
      terminal; the other was of an almost entire sequence [18-123]. We constructed
      recombinant plasmids for fusion proteins of beta-galactosidase, of
      chloramphenicol acetyltransferase, and of alkaline phosphatase. We found the
      biotinylation in the [18-123] sequence fused to alkaline phosphatase.

PMID- 1368827
TI  - Structural elucidation of minor components of peptidyl antibiotic P168s
      (leucinostatins) by tandem mass spectrometry.
AB  - Tandem mass spectrometry with a four-sector type mass spectrometer was used to
      elucidate the structures of minor components of the peptidyl antibiotic P168s
      (leucinostatins). As N-terminal fragments, ions by B-type cleavage were dominant,
      while V-type cleavages were observed along with X, Y, and Z types as C-terminal
      ions. The V-type ions were predominant in the cleavages of the amino terminals of
      leucyl and hydroxyleucyl residues. The structures of several minor components
      could be deduced from the tandem mass spectra.

PMID- 1368829
TI  - Escherichia coli beta-galactosidase production by baculovirus-insect cell system.

PMID- 1368828
TI  - Multiple rpoD-related genes of cyanobacteria.
AB  - Genomes of many eubacterial strains have been shown to encode for multiple rpoD
      related genes. In this report, we describe the identification of the multiple
      rpoD-related genes of cyanobacterial strains. DNAs of three cyanobacterial
      strains, Anabaena sp. PCC7120, Synechococcus sp. PCC7942, and Synechocystis sp.
      PCC6803, were examined by Southern hybridization, using a synthetic probe
      designed for detecting rpoD or rpoD-related genes. Four or five hybridization
      signals were found in each DNA. Four DNA regions of Synechococcus sp. PCC7942
      corresponding to the hybridization signals were cloned and partially sequenced.
      The sequence data indicate the presence of genes, named rpoD1, rpoD2, rpoD3, and
      rpoD4, whose products are highly similar to the basic structure of the principal
      sigma factors of eubacterial strains. The rpoD1 gene showed the greatest
      similarity to the sigA gene of Anabaena sp. PCC7120.

PMID- 1368830
TI  - New method for preparing 3-ketobutylidene 2-chloro-4-nitrophenyl beta
      maltopentaoside.

PMID- 1368831
TI  - Difference between the free and conjugated galacturonate residues in their color
      reaction with carbazole or m-hydroxybiphenyl reagents.

PMID- 1368832
TI  - Suppression of hydrogen peroxide-induced mammalian cytotoxicity by
      nordihydroguaiaretic acid.

PMID- 1368833
TI  - Purification of a new extracellular 90-kDa serine proteinase with isoelectric
      point of 3.9 from Bacillus subtilis (natto) and elucidation of its distinct mode
      of action.
AB  - A new extracellular 90-kDa serine proteinase with an isoelectric point (pI) of
      3.9 was purified from Bicillus subtilis (natto). Microheterogeneity was detected
      in the 50-kDa protease of bacillopeptidase F with pI 4.4 reported previously by
      Wu et al. and the sequence for the first 25 amino acids in the internal region of
      the enzyme was analyzed: ATDGVEWNVDQIDAPKAWALGYDGA. The cleavage sites in the
      oxidized B-chain of insulin by the proteinase were CySO3H7-Gly8, Val12-Glu13,
      Try16-Leu17, and Phe25-Tyr26. The activity was inhibited by phenylmethylsulfonyl
      fluoride (PMSF) and chymostatin, while the activity was not inhibited by
      proteinaceous Streptomyces subtilisin inhibitor (SSI) or alpha 2-macroglubulin.

PMID- 1368834
TI  - Casein kinase II site of human centromere protein B (CENP-B) is phosphorylated in
      vitro.

PMID- 1368835
TI  - Purification and characterization of an endoglucanase from the cellulosomes
      (multicomponent cellulase complexes) of Clostridium thermocellum.
AB  - A subunit with carboxymethyl cellulase (CMCase) activity was isolated from the
      cellulosomes of Clostridium thermocellum after dissociation of the cellulosomes
      by a mild sodium dodecyl sulfate (SDS) treatment. The subunit displayed only one
      protein band of 51 kDa on SDS-polyacrylamide gel electrophoresis (SDS-PAGE), but
      after boiling with SDS it had 3 bands of 60, 56, and 48 kDa. Prolonged incubation
      with SDS changed the subunit to display exclusively the 48-kDa band after
      boiling. The 51-kDa subunit was presumably a partially denatured form, and
      differentiated into 3 species with apparent M(r) of 60, 56, and 48 k through
      deglycosylation in SDS solution. Enzymatic properties of the 51-kDa subunit
      resembled those of the endoglucanase A which was purified from the culture fluid
      and from a E. coli clone with exceptions of temperature and pH optima.

PMID- 1368836
TI  - Purification and some properties of acidocin 8912, a novel bacteriocin produced
      by Lactobacillus acidophilus TK8912.
AB  - Acidocin 8912, a bacteriocin produced by Lactobacillus acidophilus TK8912, was
      purified by ammonium sulfate fractionation and successive chromatographies on CM
      cellulose, Sephadex G-50, Sephadex G-25, and reversed-phase HPLC on Aquapore RP
      300. The purified acidocin 8912 migrated as a single band on SDS-PAGE. The
      molecular weight was estimated to be 5200 by SDS-PAGE, and 5400 by HPLC gel
      filtration on TSKgel G3000PWXL. Both the amino acid composition and the N
      terminal amino acid sequence analysis indicated that acidocin 8912 was a peptide
      composed of presumably 50 amino acids containing a Lys residue at the N-terminus.
      The purified acidocin 8912 showed a bactericidal effect on sensitive cells but
      not a bacteriolytic effect.

PMID- 1368837
TI  - Cloning and molecular analysis of cDNA encoding a carboxymethylcellulase of the
      yeast Cryptococcus flavus.
AB  - A cDNA copy for carboxymethylcellulase (CMCase 1) of the yeast Cryptococcus
      flavus was cloned by screening an expression cDNA library with anti-CMCase 1
      antibody. The sequence of the cDNA had an open reading frame of 1023 bp that
      encoded a preprotein of 341 amino acids with a molecular weight of 35,698. The
      putative precursor begins with a hydrophobic segment that possibly acts as a
      signal sequence for secretion, which is followed by a presumed prosequence and a
      sequence consistent with the N-terminal amino acid sequence of secreted CMCase 1.
      No potential N-glycosylation site was found in the sequence of putative pro
      CMCase 1. Comparison of the deduced protein sequence shows that the C. flavus
      CMCase 1 is partially homologous to the Trichoderma reesei endoglucanase EGIII.
      Alignment of the cDNA copy and the chromosomal DNA showed seven putative introns
      of 45 to 134 bp. When introduced into E. coli, the cDNA directed the synthesis of
      CMCase 1 as seen by CMCase activity and Western blotting using anti-CMCase 1
      antibody.

PMID- 1368838
TI  - Amino acid sequences of trypsin inhibitors from oriental pickling melon (Cucumis
      melo L. var. Conomon Makino) seeds.
AB  - Three inhibitors (CMCTI-I, II, and III) were isolated from oriental pickling
      melon (Cucumis melo L. var. Conomon Makino) seeds by acetone precipitation, gel
      filtration, and reversed phase chromatography. The amino acid sequences of these
      inhibitors were: [table; see text] The reactive sites (P1 and P1' sites) of these
      inhibitors are presumed to be the Lys-Ile indicated by an arrow, comparing them
      with other squash family inhibitors. All three inhibitors can inhibit lysyl
      endopeptidase and trypsin at the enzyme-inhibitor ratio of 1:1.

PMID- 1368839
TI  - Effects of butyrate on cell cycle progression and polyploidization of various
      types of mammalian cells.
AB  - We studied the effect of butyrate on cell cycle progression and polyploidization
      in three fibroblast (rat 3Y1, human IMR-90, and human embryo lung HEL) and two
      epithelial (human embryo kidney HEK and monkey kidney BSC-1) cells. In these
      cells, except for 3Y1, G1 arrest with butyrate was incomplete, and the production
      of tetraploid cells was detectable in the presence of butyrate. G2 arrest with
      butyrate was also incomplete in HEL and BSC-1 cells, and the number of HEL cells
      increased in the presence of butyrate. On the contrary, most BSC-1 cells that
      divided in the presence of butyrate were unstable and the number of attached
      cells decreased. These results indicate that the effect of butyrate on cell cycle
      progression varies with the cell type and that polyploidization can be induced by
      a single treatment with butyrate.

PMID- 1368841
TI  - Analysis of O-phosphoamino acids in the protein fractions of mouse tissue by gas
      chromatography.

PMID- 1368840
TI  - Degradation of streptomyces metalloprotease inhibitor (SMPI) by neutral protease
      from Bacillus subtilis var. amylosacchariticus.
AB  - The zinc-containing neutral endopeptidase (neutral protease: BANP) from Bacillus
      subtilis var. amylosacchariticus was inhibited by the proteinaceous
      metalloprotease inhibitor isolated from Streptomyces nigrescens (SMPI). The
      degree of inhibition was, however, significantly less than that for thermolysin
      (TLN). During incubation of BANP with SMPI, the inhibitor was proteolytically
      degraded and inactivated. Analysis of the digestion products suggested that a
      minor diversity in their substrate specificities between TLN and BANP affects the
      sensitivity to the proteinaceous metalloprotease inhibitor, SMPI.

PMID- 1368842
TI  - Structures and antitumor activities of polysaccharides isolated from mycelium of
      Volvariella volvacea.

PMID- 1368843
TI  - Cloning and sequencing of the xynC gene encoding acid xylanase of Aspergillus
      kawachii.

PMID- 1368844
TI  - Partial amino acid sequences of soybean lipoxygenase L-6 isolated from
      cotyledons.

PMID- 1368845
TI  - Rapid assay of glucoamylase using a fluorescence-labeled glucoamylase inhibitor,
      acarbose.

PMID- 1368846
TI  - DNA polymorphisms generated by arbitrarily primed PCR in rice.

PMID- 1368847
TI  - Whole-cell enzyme electrodes based on mediated bioelectrocatalysis.

PMID- 1368848
TI  - Bactericidal action of lysozyme against gram-negative bacteria due to insertion
      of a hydrophobic pentapeptide into its C-terminus.

PMID- 1368849
TI  - Complete amino acid sequence of crystalline alpha-glucosidase from Aspergillus
      niger.

PMID- 1368850
TI  - A new high-mannose type N-linked oligosaccharide from Aspergillus
      carboxypeptidase.

PMID- 1368851
TI  - Snake venom: "gentler" purification provides attractive nerve growth factor
      source.

PMID- 1368852
TI  - Elimination of PCR carryover.

PMID- 1368853
TI  - Advantages of vertical isoelectric focusing slab gels.

PMID- 1368854
TI  - Effect of culture method on glycosylation pattern of a murine IgG monoclonal
      antibody.

PMID- 1368855
TI  - NMR spectroscopy in the structural elucidation of oligosaccharides and
      glycosides.
AB  - The potential of one- and two-dimensional NMR techniques for the identification
      of individual sugar residues, their anomeric configuration, interglycosidic
      linkages, sequencing and the site of any appended group, in establishing the
      structures of naturally occurring oligosaccharides and glycosides is presented.

PMID- 1368856
TI  - Large-scale purification and preliminary structural studies of MAC 182, a
      gibberellin-binding monoclonal antibody.
AB  - The large-scale purification of the anti-gibberellin monoclonal antibody, MAC
      182, is described. N-Terminal amino acid sequences of the heavy and light chains
      were determined and compared with those of known antibodies. Fab-fragments were
      prepared and purified to a state suitable for crystallization.

PMID- 1368857
TI  - Biologically active diterpenes from Aspilia mossambicensis, a chimpanzee
      medicinal plant.
AB  - Two potent stimulators of uterine contraction, the diterpenes kaurenoic and
      grandiflorenic acids, were isolated from leaves of Aspilia mossambicensis. Their
      presence supports a hypothesis that wild chimpanzees consume Aspilia species for
      their pharmacological properties and may explain why female chimpanzees consume
      Aspilia leaves more frequently than do males. Thiarubrines were not present in
      any of the leaf samples collected in Mahale or Gombe National Parks, Tanzania,
      although these antifungal and nematocidal dithianes were found in significant
      amounts in roots.

PMID- 1368859
TI  - An unusual glucomannan from Tornabenia intricata.
AB  - Mannose-containing polysaccharides of 18 lichen species were prepared via
      successive alkaline extraction, precipitation with Fehling solution and
      fractional precipitation with Cetavlon. Products from Fehling and Cetavlon
      precipitation, the latter at pH 8.5 in the presence of borax, were structurally
      similar, except with those of Usnea sp., U. meridionalis, Parmotrema araucaria
      and Evernia prunastri, which were mixtures and initially provided precipitates at
      pH 7 due to the presence of carboxyl groups. With one exception, glucosyl units
      were detected in all preparations, but possibly arose from glucan contaminants of
      the galactomannans. Tornabenia intricata, however, did not contain galactose, and
      a glucomannan was isolated. It consisted of two components with M(r)s of ca 0.85
      x 10(5) and ca 1.1 x 10(5) and whose 13C NMR spectra were identical. The overall
      preparation contained a (1-->6)-linked alpha-D-Manp main-chain substituted at 0-2
      mainly with side chains of alpha-D-Manp with smaller amounts of alpha-D-Glcp,
      alpha-D-Glcp-(1-->2)-[alpha-D-Manp-(1-->4)]-alpha-D-Manp, and possibly alpha-D
      Manp-(1-->2)-[alpha-D-Manp-(1-->4)]-alpha-D-Manp+ ++.

PMID- 1368858
TI  - Rice seed globulin: a protein similar to wheat seed glutenin.
AB  - The globulin of the seed endosperms of rice has an isoelectric point of 6.4 and a
      M(r) of 26,000. There is one intra-disulphide bond, but no N-linked
      oligosaccharide chain. The amino acid sequence of the N-terminal and internal
      regions of the globulin was determined and found to be homologous with that of
      glutenin, the storage protein in the seed endosperms of wheat. Rice globulin and
      wheat glutenin were rich in glycine, and glutamic acid or glutamine, and in
      addition, wheat glutenin cross-reacted with antibody raised against rice
      globulin. These results suggest that rice seed globulin represents a protein
      similar to wheat seed glutenin.

PMID- 1368860
TI  - Sesquiterpenoids and iridoid glycosides from Valeriana fauriei.
AB  - A new guaiane sesquiterpenoid glycoside together with known sesquiterpenoids and
      iridoid glycosides have been isolated from the rhizomes and roots of Valeriana
      fauriei. The 13C NMR assignments of the isolated compounds are presented.

PMID- 1368861
TI  - Sesquiterpenoids from the roots of Homalomena aromatica.
AB  - From roots of Homalomena aromatica three new sesquiterpene alcohols, 1 beta, 4
      beta, 7 alpha-trihydroxyeudesmane, homalomenol A, and homalomenol B were isolated
      together with oplopanone, oplodiol and bullatantriol. The structures of the new
      constituents were elucidated by spectroscopic investigations and chemical
      transformations.

PMID- 1368862
TI  - Steroid saponins from Polygonatum kingianum.
AB  - Four new steroid saponins, kingianosides A-D, were isolated from the rhizome of
      Polygonatum kingianum, together with two known steroid saponins. On the basis of
      chemical and spectral evidence, the structures of kingianosides A-D were
      established as gentrogenin 3-O-beta-D-glucopyranosyl (1-->4)-beta-D
      galactopyranoside, gentrogenin 3-O-beta-D-glucopyranosyl(1-->4)-beta-D
      fucopyranoside, 26-O-beta-D-glucopyranosyl-22-hydroxy-25(R)-furost-5-en-12-on-3
      beta, 22-diol 3-O-beta-D-glucopyranosyl(1-->4)-beta-D-galactopyranoside and 26-O
      beta-D-glucopyranosyl-22-hydroxy-25(R)-furost-5-en-12-on-3 beta,22-diol 3-O-beta
      D-glucopyranosyl(1-->4)-beta-D-fucopyranoside, respectively.

PMID- 1368863
TI  - Balanitoside, a furostanol glycoside, and 6-methyldiosgenin from Balanites
      aegyptiaca.
AB  - In addition to a known spirostanol glycoside, balanitin-3, and a new sapogenol, 6
      methyldiosgenin, a new furostanol saponin, balanitoside has been isolated from
      the fruits (mesocarp) of Balanites aegyptiaca. The structure of the glycoside has
      been determined as 26-O-beta-D-glucopyranosyl-3 beta, 22,26-trihydroxy-furost-5
      ene 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D- glucopyranosyl-(1-->4)-beta-D
      glucopyranoside, on the basis of spectroscopic and chemical evidence.

PMID- 1368864
TI  - Saponins from stem bark of Petersianthus macrocarpus.
AB  - Two bioactive saponins were isolated from the stem bark of Petersianthus
      macrocarpus. Their structures were elucidated by chemical degradations and by a
      combination of 2D NMR techniques and by Californium plasma desorption mass
      spectrometry. They are 3-O-([beta-D-galactopyranosyl (1-->2)][beta-D
      galactopyranosyl (1-->3)]- beta-D-glucuronopyranosyl)-21-O-[3-(3-tigloyloxynilic
      acid)-4-tigloyloxy- alpha-L-arabinopyranosyl] barringtogenol C and 3-O-([beta-D
      galactopyranosyl (1-->2)][beta-D-galactopyranosyl (1-->3)]-beta-D
      glucuronopyranosyl)-28-O-alpha-L-rhamnopyranosyl barringtogenol C-21-O-benzoate.
      The absolute configuration of nilic acid was determined by partial synthesis.
      3,3'-Dimethoxy ellagic acid and 3,3'-dimethoxy-4-O-beta-D- glucopyranosyl ellagic
      acid were also isolated.

PMID- 1368865
TI  - Phenylpropanoid glycosides from Marrubium alysson.
AB  - From the aerial parts of Marrubium alysson a new phenylpropanoid glycoside,
      alyssonoside, and five known glycosides, verbascoside (= acteoside),
      leucosceptoside A, martynoside, forsythoside B and leucosceptoside B were
      isolated. On the basis of spectral data, the structure of the new compound was
      elucidated as beta-(3,4-dihydroxyphenyl)ethyl-O-[alpha-L-rhamnopyranosyl-(1-->3)]
      O- [beta-D-apiopyranosyl-(1-->6)]-4-O-feruloyl-beta-D-glucopyra noside.

PMID- 1368866
TI  - Inhibition of wheat embryo calcium-dependent protein kinase and other kinases by
      mangostin and gamma-mangostin.
AB  - The hull of the fruit of the mangosteen tree (Garcinia mangostana) contains four
      inhibitors of plant Ca(2+)-dependent protein kinase. Two of these inhibitors have
      been purified and identified as the xanthones 1,3,6-trihydroxy-7-methoxy-2,8
      bis(3-methyl-2-butenyl)-9H- xanthen-9-one (mangostin) and 1,3,6,7-tetrahydroxy
      2,8-bis(3-methyl-2-butenyl)- 9H-xanthen-9-one (gamma-mangostin). Both xanthones
      also inhibit avian myosin light chain kinase and rat liver cyclic AMP-dependent
      protein kinase. This is the first report of inhibition of plant and animal second
      messenger-regulated protein kinases by plant-derived xanthones.

PMID- 1368868
TI  - Determination of the rate-limiting step(s) in the biosynthetic pathways leading
      to penicillin and cephalosporin.
AB  - This paper is a review of strategies that have been used, or that could be used,
      to determine the rate-limiting step(s) in the biosynthetic pathways leading to
      penicillin or cephalosporin. Information is summarized from published material
      that involves studies with low-producing strains of Penicillium chrysogenum and
      Cephalosporium acremonium. We also summarize information derived from some high
      producing production strains. Identification of the rate-limiting step(s) was of
      great interest to us as the first step in a rational program to further improve
      antibiotic titers of these highly developed strains. A number of approaches that
      could be used to elucidate the rate-limiting step(s) are described herein.

PMID- 1368870
TI  - Glycoprotein glycans--roles and controls.

PMID- 1368871
TI  - Human serum albumin structure--solved.

PMID- 1368869
TI  - Effect of cell immobilization and organic solvents on sulfoxidation and steroid
      hydroxylation by Mortierella isabellina.
AB  - The effects of calcium alginate bead immobilization and the presence of organic
      solvents on two bioconversion reactions carried out by Mortierella isabellina
      ATCC 42613 have been investigated. These reactions, the 14 alpha-hydroxylation of
      progesterone and the sulfoxidation of thioanisole, both proceed in high yield
      using resting-cell bioconversions, but are not carried out by alginate bead
      preparations in the absence of an organic co-solvent, the best results being
      obtained with 5 or 10% aqueous methanol. The stereoselectivity of sulfoxidation
      of thioanisole was found to be dependent upon the nature and concentration of
      organic co-solvent.

PMID- 1368867
TI  - Thom Award Lecture. Trends in the search for bioactive microbial metabolites.
AB  - Bioactive microbial metabolites are attracting increasing attention as useful
      agents for medicine, veterinary medicine, agriculture, and as unique biochemical
      tools. A review of the current trends in the discovery of new metabolites shows
      that the number of active compounds with non-antibiotic type of activity has
      increased, resulting in an expansion of the variety of bioactivity of microbial
      metabolites. Factors that contribute to the increased rate of discovery include:
      development of new methods for activity measurement, exploitation of novel groups
      of microorganisms as sources of active compounds, new directions for chemical
      modification, and incorporation of newer knowledge of biotechnology into
      screening systems. To exemplify this, typical screening methods, and chemical and
      biological properties of several bioactive compounds obtained by these methods
      are discussed.

PMID- 1368872
TI  - Engineering enzymes for chemoenzymatic synthesis. Part I: Practical routes to aza
      sugars and complex carbohydrates.

PMID- 1368873
TI  - Image analysis: putting filamentous microorganisms in the picture.
AB  - Image analysis can be used to characterize the morphology and simple
      differentiation of fungi and actinomycetes. It provides a new and powerful tool
      for the physiologist or fermentation technologist working with filamentous
      microorganisms.

PMID- 1368874
TI  - Erythropoietin and myeloid colony stimulating factors.
AB  - The production of blood cells in the body is controlled by at least 20
      polypeptide growth factors. Most of these factors have been cloned and many
      expressed in bacterial and eukaryotic systems to give biologically active
      proteins. Currently, these recombinant human proteins are undergoing intensive
      evaluation for their use in treating primary haemopoietic diseases, or
      stimulating normal haemopoiesis following drug-, radiation- or virus-induced
      trauma of the bone marrow. Erythropoietin (EPO) and the myeloid colony
      stimulating factors (IL-3, G-CSF, GM-CSF and M-CSF) were among the first to be
      cloned and expressed.

PMID- 1368875
TI  - Computer-aided drug design: getting the best results.
AB  - There are two major stages in the design of drug molecules: lead-molecule
      development and lead-molecule optimization. Whereas a variety of computational
      chemistry and molecular modeling (CC/MM) techniques are now routinely and
      successfully applied to the optimization stage of drug design, the generation of
      initial lead compounds has proven a more difficult problem for the CC/MM
      approach. Only recently has the design of lead molecules by this route become a
      subject of active research. This article looks at the factors which must be
      considered carefully when incorporating CC/MM methods into different aspects of
      drug-design strategies.

PMID- 1368877
TI  - Pores for thought in bioseparation and bioassay matrices.

PMID- 1368876
TI  - Deamidation: a source of microheterogeneity in pharmaceutical proteins.
AB  - Most protein molecules undergo some degree of spontaneous deamidation in vivo.
      This process may also occur during the production, isolation, purification,
      formulation and storage of pharmaceutical proteins. Deamidation is a potential
      source of microheterogeneity for pharmaceutical proteins, and this is an
      important issue that needs to be addressed, not only by the manufacturers but
      also by the national control agencies. This article provides an overview of the
      scientific and regulatory issues pertinent to deamidation of pharmaceutical
      proteins.

PMID- 1368878
TI  - What's immoral in patent law?

PMID- 1368879
TI  - Engineering enzymes for chemoenzymatic synthesis. Part 2: Modifying proteases for
      peptide synthesis.

PMID- 1368880
TI  - Malaria transmission-blocking vaccines.
AB  - Antibodies to surface proteins of the sexual stages of Plasmodium falciparum
      block completely the transmission of these malaria parasites. Transmission
      blocking vaccines therefore represent a powerful and novel approach to
      controlling the spread of this lethal disease.

PMID- 1368881
TI  - A perspective on the biotechnological potential of extremophiles.
AB  - It is well recognized that many environments considered by man to be extreme are
      colonized by microorganisms which are specifically adapted to these ecological
      niches. A diverse range of bacteria, cyanobacteria, algae and yeasts have been
      isolated from such habitats and it is now widely accepted that these
      microorganisms provide a valuable resource not only for exploitation in novel
      biotechnological processes but also as models for investigating how biomolecules
      are stabilized when subjected to extreme conditions. This short review summarizes
      our current state of knowledge of this unique group of microorganisms and their
      enzymes, and attempts to identify their future biotechnological potential.

PMID- 1368882
TI  - Enzymatic synthesis of acrylamide: a success story not yet over.
AB  - The application of enzymatic transformations is attracting increasing attention.
      Until recently, such an approach has generally been confined to producing fine
      chemicals difficult to obtain through conventional chemical methods. Microbial
      nitrile hydratase (NHase) has now been applied to the industrial, kiloton-scale
      production of the important chemical commodity acrylamide. Recent progress in
      understanding microbial nitrile metabolism at both the gene and protein levels is
      permitting improvement of the acrylamide production process.

PMID- 1368883
TI  - Large-scale processing & high-throughput perfusion chromatography.

PMID- 1368884
TI  - Teaching self-tolerance: biotech autoimmune therapies.

PMID- 1368885
TI  - Biotechnology and economic development: the winning formula.

PMID- 1368886
TI  - The first of the big spenders.

PMID- 1368887
TI  - Runaway-replication plasmids as tools to produce large quantities of proteins
      from cloned genes in bacteria.
AB  - Here we review the properties and uses of runaway-replication vectors, a class of
      versatile plasmids discovered and developed in Escherichia coli. They are based
      on the IncFII plasmid, R1, in which an antisense RNA (CopA RNA) negatively
      controls the formation of a protein that is rate-limiting for replication. The
      copy number of the plasmid is determined by the balance between the rates of
      formation of CopA RNA and RepA mRNA. A small increase in the rate of formation of
      the latter drastically reduces the rate of formation of CopA RNA due to
      convergent transcription, which may lead to a total loss of copy number control
      (runaway replication), resulting in massive DNA amplification, and plasmid copy
      numbers up to 1000 per genome. Since this amplification occurs in the presence of
      protein synthesis, the protein that is encoded by a cloned gene can also be
      amplified, and may constitute 10-50% of the total protein.

PMID- 1368888
TI  - Single tree genetic linkage mapping in conifers using haploid DNA from
      megagametophytes.
AB  - We report a unique application of the Random Amplified Polymorphic DNA (RAPD)
      technique for genetic linkage mapping of a single spruce tree using haploid DNA
      from megagametophyte tissue of individual seeds. Sixty-one segregating loci were
      analysed for reproducibility, inheritance and linkage. Forty-seven of the 61
      markers were distributed into 12 linkage groups and covered 873.8 cM. The 14
      markers not associated with any linkage group should be assigned to linkage
      groups as more markers are added to the map. This new approach quickly provides
      molecular genetic markers that are simple to evaluate for constructing genetic
      linkage maps and for other related genetic studies in forest tree species.

PMID- 1368889
TI  - Kinetic analysis of recombinant antibody-antigen interactions: relation between
      structural domains and antigen binding.
AB  - The relation between domain structures of recombinant monoclonal antibody
      fragments and their reaction kinetics was studied for the first time using a
      novel biosensor based on surface plasmon resonance technology. The association
      and dissociation rate constants of Fab, Fv and single domain (VH fragment) anti
      lysozyme antibodies were determined and compared to the intact monoclonal
      antibody. Fab and Fv fragments showed similar reaction kinetics and had affinity
      constants of 6 x 10(9) M-1 and 25 x 10(9) M-1, respectively. The single domain
      antibody had significantly different reaction kinetics compared to the fragments
      consisting of paired heavy and light chain domains. The VH domain had both a
      higher dissociation and a lower association rate constant, which resulted in an
      affinity constant approximately 250 times lower than the Fab fragment. This rapid
      evaluation of antibody reaction kinetics should prove to be an important
      selection parameter when comparing antibody fragments for their utility in
      therapeutic or other applications.

PMID- 1368890
TI  - Screening of whole-cell immobilization procedures for the delta 1-dehydrogenation
      of steroids in organic medium.
AB  - Different whole-cell immobilization methods and conditions were tested for the
      delta 1-dehydrogenation of 6-alpha-methyl-hydrocortisone-21-acetate with
      Arthrobacter simplex cells, in n-decane-1-ol and chloroform. Among the entrapment
      methods, polyurethane foams gave the best productivity of n-decane-1-ol, but
      could not be used in chloroform. Partition and diffusional barriers appeared to
      be the factors limiting productivity in entrapped-cell systems. The coentrapment
      of enzyme-stabilizing (glycerol, sucrose, sodium sulfate, monosodium glutamate)
      or hydrophobic additives did not significantly improve dehydrogenation rates in
      chloroform, although in some cases higher activities resulted in n-decane-1-ol.
      Dehydration of kappa-carrageenan-immobilized cells lowered the productivity in
      both solvents. The use of cell adsorption methods on silica-based carriers
      produced biocatalysts that in some cases were more active in chloroform than the
      entrapped cells. However, the surface-attached cells appeared to be more
      sensitive to solvent toxicity, more hydrophilic supports generally giving higher
      dehydrogenation rates. The estimated partition coefficients for the substrate
      between several of the tested supports and the two solvents are also presented.
      High partition ratios followed high measured activities in entrapment matrices
      but not in Celite (cell adsorption matrix). Activities in chloroform were always
      very low (less than 1 mumol product per hour and gram of cell dry weight).
      Polyurethane entrapment with n-decane-1-ol as a reaction medium was the most
      promising system, with measured dehydrogenation rates up to 40 times higher.

PMID- 1368891
TI  - Functional and structural relationships among aldose reductase, L-hexonate
      dehydrogenase (aldehyde reductase), and recently identified homologous proteins.

PMID- 1368892
TI  - Heterologous expression of thermopsin, a heat-stable acid proteinase.
AB  - We have previously reported the isolation, characterization, and gene sequence of
      a new thermostable acid protease, thermopsin, from Sulfolobus acidocaldarius, a
      thermophilic archaebacterium. Thermopsin is similar to aspartic protease pepsin
      in specificity and pH dependence. However, it optimally catalyzes in the
      temperature range of 85 to 90 degrees C and it is not structurally related to
      pepsin. The current report describes the synthesis of recombinant thermopsin in
      E. coli and in insect cells. Several recombinant thermopsin fusion proteins were
      expressed as "inclusion bodies" in the cytosol of E. coli. Active thermopsin
      preparations were obtained by refolding from urea solutions. Recombinant
      thermopsin was also expressed in insect cells using a baculovirus expression
      system. The thermostability of recombinant thermopsin is similar to that of the
      native enzyme.

PMID- 1368893
TI  - A kinetic study of immobilized lipase catalysing the synthesis of isoamyl acetate
      by transesterification in n-hexane.
AB  - Isoamyl acetate was synthesized by lipase-catalyzed transesterification of ethyl
      acetate in n-hexane. The selectivity and rates of ester formation decreased when
      water content of the immobilized enzyme exceeded 3% (w/w). Experimental
      observations clearly indicate that the substrates as well as the product
      (ethanol) act as dead-end inhibitors. A ping-pong bi-bi mechanism with
      competitive inhibition by substrates and products is proposed that predicts the
      experimental observation satisfactorily.

PMID- 1368894
TI  - Counter-diffusion of lactose and lactic acid in kappa-carrageenan/locust bean gum
      gel beads with or without entrapped lactic acid bacteria.
AB  - The effective diffusion coefficient (De) and equilibrium partition factor (Kp)
      for lactose and lactic acid in k-carrageenan (2.75% w/w)/locust bean gum (0.25%
      w/w) (LBG) gel beads (1.5-2.0 mm diameter), with or without entrapped
      Lactobacillus casei subsp. casei (L. casei), were determined at 40 degrees C.
      Results were obtained from transient concentration changes in well-stirred
      solutions of finite volume in which the beads were suspended. Mathematical models
      of unsteady-state diffusion into and/or from a sphere and appropriate boundary
      conditions were used to calculate effective diffusion coefficients of lactose and
      lactic acid from the best fit of the experimental solute concentration changes.
      The effective diffusivities of lactose and lactic acid were 5.73 x 10(-10) and
      9.96 x 10(-10) m2 s-1, respectively. Furthermore, lactic acid was found to modify
      gel structure since lactose diffusion characteristics (De and Kp) differed
      significantly from an earlier study and in the literature. In gel beads heavily
      colonized with L. casei, the effective diffusion coefficients of lactose and
      lactic acid were respectively 17% and 24% lower than for cell-free beads.
      Partition coefficients also confirmed the obstruction effect due to the cells,
      and decreased from 0.89 to 0.79, and from 0.98 to 0.87, for lactose and lactic
      acid, respectively. External mass transfer was estimated by an unsteady-state
      model in infinite volume using the Biot number. The effect of external mass
      transfer resistance on De results and the data reported in the literature are
      discussed.

PMID- 1368896
TI  - Efficient secretion of human lysozyme fused to the Sh ble phleomycin resistance
      protein by the fungus Tolypocladium geodes.
AB  - Tolypocladium geodes strain NC50 was transformed by different integrating vectors
      bearing both a synthetic gene encoding human lysozyme (HLz) and the Sh ble
      phleomycin resistance marker, either in separate expression cassettes or in
      transcriptional or translational fusion configurations. Clones derived from all
      vectors were able to secrete HLz. The highest productivities in shake flasks (up
      to 150 mg l-1 in 5 days) were obtained when HLz was fused at the C-terminal end
      of the Sh ble protein. The fusion protein is efficiently secreted and release of
      active lysozyme occurs by extracellular proteolytic cleavage in the junction
      peptide.

PMID- 1368895
TI  - Plasmid instabilities of single and three-plasmid systems in Escherichia coli
      during continuous cultivation.
AB  - Plasmid instabilities in E. coli JM103 carrying three plasmids (pRK248cI, pMTC48,
      pEcoR4) and a single plasmid system (pTG206) for the production of fusion EcoRI
      (SPA::EcoRI) and catechol 2,3-dioxygenase, respectively, were investigated in
      continuous cultures under selective and non-selective conditions. In a three
      plasmid system, pRK248cI was lost gradually together with pMTC48 from the host
      under non-selective conditions. The selective pressure against pRK248cI
      stabilized the pMTC48. This indicates that the loss of pMTC48 under non-selective
      conditions was caused by the loss of cI857 gene (coded by pRK248cI) which
      resulted in the overproduction of the toxic gene product (coded by pMTC48). In
      the case of single plasmid (pTG206) system, the plasmid lost from the host under
      non-selective conditions. This plasmid was stabilized in the host growing under
      selective conditions. During this period we obtained some ampicillin resistant
      colonies which gave low levels of enzyme activities compared to the normal
      plasmid bearing cells. Plasmid analysis from the above cells showed that the
      plasmid has undergone structural instability. Further, restriction analysis of
      this plasmid exhibited an additional PvuII site in a 0.9 kbp fragment that was
      integrated near the tet promoter which controls the expression of the xyl E gene,
      thereby resulting low levels of enzyme activities. Our results indicate that some
      of the IS elements which are present in the host chromosome were responsible for
      such instabilities to turn off the synthesis by inserting into the tet promoter
      region to lower the protein formation during the bioprocess.

PMID- 1368897
TI  - Mitotic instability of integrated plasmids in Penicillium chrysogenum
      transformants.
AB  - Transformation vectors based on the Streptoalloteichus hindustanus phleomycin
      resistance gene placed under the control of either the Penicillium chrysogenum
      trpC or pcbC promoters were constructed (plasmids pGS1 and pGS7 respectively). Up
      to 100 transformants per microgram of DNA were obtained with pGS7 in P.
      chrysogenum strain P2. In order to follow the expression of additional penicillin
      biosynthetic genes introduced by transformation, a pcbC::lacZ gene fusion was
      introduced into pGS1, generating pGS6. Southern analysis of three pGS6
      transformants indicated that the plasmid was integrated in tandem arrays.
      Revertants which had lost the exogenous beta-galactosidase activity, were
      detected for each transformant after several cycles of subculture on non
      selective medium. Southern analysis indicated that the different phenotypes
      obtained resulted from the loss of part or all of the integrated plasmid copies.

PMID- 1368898
TI  - Optimization of a process for the production of (R)-2-hydroxy-4-phenylbutyric
      acid--an intermediate for inhibitors of angiotensin converting enzyme.
AB  - (R)-2-Hydroxy-4-phenylbutyric acid, an intermediate in the manufacture of
      inhibitors of angiotensin converting enzyme, can be produced continuously in an
      enzyme membrane reactor by enzymatic reduction of its corresponding alpha-keto
      acid. D-Lactate dehydrogenase (D-LDH) from Staphylococcus epidermidis was chosen
      as the most appropriate enzyme to carry out the NADH-dependent reduction. Formate
      dehydrogenase (FDH) was used for NADH regeneration. Detailed kinetic measurements
      and a mathematical model for the coupled enzyme reactions were applied to
      calculate the optimal conditions for continuous production of the alpha-hydroxy
      acid. A mass of 1 kg [corrected] (R)-2-hydroxy-4-phenylbutyric acid was
      synthesized in a 220 ml enzyme membrane reactor over a period of 4 weeks. A mean
      space-time-yield of 165 g l-1 d-1 was achieved at low enzyme consumptions of 150
      U kg-1 alpha-hydroxy acid for FDH and D-LDH.

PMID- 1368899
TI  - Permeation of 6-nitro-3-phenylacetamide benzoic acid (NIPAB) and hydrolysis by
      penicillin acylase immobilized in emulsion liquid membranes.
AB  - The effects of various commercial and model surfactants of different structure
      and hydrophilicity were studied on water-in-oil (w/o) emulsion stability,
      potassium cation leakage and permeation of 6-nitro-3-phenylacetamide benzoic acid
      in a model system using Penicillin acylase (EC 3.5.1.11) immobilized in a liquid
      membrane. Both emulsion stability, potassium leakage and permeation of organic
      substances depend upon hydrophilicity of surfactants. Hydrophilic surfactants may
      be used to stabilize emulsions only in mixtures with hydrophobic emulsifiers.
      Additions of small quantities of hydrophilic surfactants to the system in which
      permeation occurs together within an enzymatic process may be advantageous. Both
      the rate of permeation and potassium transfer significantly increase when
      hydrophilic surfactants are present. There was no relationship observed between
      potassium cation transfer from the internal phase and emulsion stability in the
      storage test.

PMID- 1368900
TI  - Thermal inactivation kinetics of penicillin G acylase obtained from a mutant
      derivative of Escherichia coli ATCC 11105.
AB  - Thermal inactivation kinetics of native and glutaraldehyde cross-linked forms of
      penicillin G acylase obtained from a mutant derivative of Escherichia coli ATCC
      11105 were studied. Apparent activation energies for thermal inactivation of both
      native and cross-linked forms of enzyme were calculated to be [57.71 +/- 8.46]
      and [67.11 +/- 13.83] kcal mol-1 respectively. This slight increase in activation
      energy suggested that glutaraldehyde cross-linking did not markedly protect
      against thermal activation. Cross-linked enzyme did, however, have a
      significantly improved half-life at temperatures between 40 degrees C and 50
      degrees C.

PMID- 1368901
TI  - The use of modified divinylbenzene-polystyrene resins in the separation of
      fermentation products. A case study utilizing amino acids and a dipeptide.
AB  - The adsorption of phenylalanine, aspartic acid, asparagine and aspartame from
      phosphate-buffered aqueous solutions with modified divinyl-benzene-polystyrene
      resins has been investigated using high pressure liquid chromatography (HPLC).
      The pH studied was 2.8, the temperature range was 293-313 K and the ionic
      strength was maintained at 1.0 mol dm-3. Over the range of variables
      investigated, the adsorption isotherms are linear and may be characterized by
      temperature and pH-dependent apparent adsorption equilibrium constants,
      characteristic of the resin-adsorbate system. By studying the dependence on
      temperature of this adsorption constant, heats of adsorption and entropy of
      adsorption have been estimated. In terms of the heat liberated on adsorption, the
      amino acids and a dipeptide can be ranked thus: aspartame > phenylalanine >
      aspartic acid > asparagine.

PMID- 1368902
TI  - A study on the removal of urea from aqueous solution with immobilized urease and
      electrodialysis.
AB  - A five-compartment electrodialyzer with immobilized urease was developed for the
      removal of urea from aqueous solution. The immobilized urease, supported on
      polyurethane foam, was placed in the central (dilute) compartment, where urea was
      hydrolyzed and the products NH4+ and CO3(2-)/HCO3- were removed simultaneously by
      electrodialysis. The system was studied both under constant current and under
      constant voltage. The effects of urea concentration and applied current or
      voltage on the removal of urea and ammonium ions from the dilute solution were
      investigated. The variations of the pH of dilute solution, the current or voltage
      of system, and current efficiency were also examined during reaction
      electrodialysis. The removal of urea by enzymic reaction was not affected
      significantly by the applied electric field. The current efficiencies for
      removing ammonium ions from dilute solution were mostly within 40-80%, and the
      removal percentage of ammonium ions was dependent on current density and current
      efficiency.

PMID- 1368903
TI  - Isolation and identification of ethisolide as an antibiotic product from
      Penicillium capsulatum.
AB  - Ethisolide has been isolated from cultures of Penicillium capsulatum, and its
      structure determined by means of infrared, mass spectrometry, 1H- and 13C nuclear
      magnetic resonance. Antibiotic activity against a number of microorganisms is
      reported.

PMID- 1368904
TI  - Rabbit articular chondrocytes in alginate gel: characterisation of immobilized
      preparations and potential applications.
AB  - Primary cultivated rabbit articular chondrocytes were immobilized in calcium
      alginate beads. Both free and entrapped cells were allowed to grow under normal
      conditions. After long-term immobilization, the cells still exhibited metabolic
      activities, patterns of division, synthesis and secretion of extracellular matrix
      macromolecules such as type II collagen and proteoglycans. After 38 days,
      immobilized rabbit articular chondrocytes predominantly expressed type II but not
      type I collagen. Thus, they maintained their cartilage pheno-type. After bead
      lysis, harvested cells showed normal growth patterns when resuspended in culture
      medium. On the basis of these results, long-duration storage and large-scale
      production of extracellular matrix components are being investigated.

PMID- 1368905
TI  - A packed-bed reactor utilizing porous resin enables high density culture of
      hepatocytes.
AB  - To enable high density culture of hepatocytes for use as a hybrid artificial
      liver support system or a bioreactor system, a packed-bed reactor using collagen
      coated reticulated polyvinyl formal (PVF) resin was applied to a primary culture
      of hepatocytes. Cubic PVF resins (2 x 2 x 2 mm, mean pore size: 100, 250 or 500
      microns) were used as supporting substrates to immobilize hepatocytes. Two
      hundred and fifty cubes were packed in a cylindrical column, and 2.6-11.3 x 10(7)
      hepatocytes were seeded in the column by irrigating with 3 ml of the medium
      containing hepatocytes. Perfusion culture experiments using this packed-bed
      reactor, as well as monolayer cultures using conventional collagen-coated petri
      dishes as control experiments, were performed. Sufficient amounts of hepatocytes
      were found to be immobilized in the reticulated structure of the PVF resins. The
      highest density of immobilized hepatocytes attained with PVF resin was 1.2 x
      10(7) cells/cm3 PVF, which showed levels of ammonium removal and urea-N secretion
      comparable to those in the monolayer culture. It is concluded that the packed-bed
      reactor system utilizing PVF resin is a promising process for developing a
      bioreactor or a bioartificial organ using hepatocytes.

PMID- 1368906
TI  - Proteolytic response to the expression of an abnormal beta-galactosidase in
      Escherichia coli.
AB  - Because induction of proteolytic activity and stress-response proteins can
      significantly affect expression levels in recombinant Escherichia coli, the
      influence of low-level expression of a mutant beta-galactosidase was
      investigated. A single copy of the well-characterized CSH11 mutant of the lacZ
      gene was integrated into the chromosome. Induction of expression of the mutant
      beta-galactosidase caused a measurable increase in ATP-dependent intracellular
      proteolytic activity but resulted in no significant change in ATP-independent
      proteolytic activity. Growth at temperatures above 40 degrees C resulted in a
      significant decrease in the level of ATP-independent proteolytic activity
      compared to growth at 37 degrees C, and the ATP-dependent activity increased 2.5
      fold from 30 to 42 degrees C. Synthesis of stress-response proteins was evident
      in two-dimensional gel electrophoresis analysis of proteins in the strain
      expressing the abnormal beta-galactosidase at 37 degrees C, but no such response
      was evident when mutant beta-galactosidase expression was induced at 30 degrees
      C. In separate experiments, stress proteins were overexpressed by inducing
      expression of the htpR gene on a plasmid. Resulting increases in stress-protein
      levels correlated with an increase in ATP-dependent proteolytic activity with no
      significant change in the intracellular ATP-independent proteolytic activity.
      These data suggest that even very low levels of abnormal protein can
      substantially influence protease levels and stress response in E. coli. These
      responses were reduced by induction at lower temperatures.

PMID- 1368908
TI  - Secretion of a functional Fab fragment in Escherichia coli and the influence of
      culture conditions.
AB  - Genes encoding a light chain and an Fd region (a variable region and a CH1 domain
      of a heavy chain) of a mouse-human chimeric antibody with specificity for human
      carcinoembryonic antigen (CEA) were fused to a DNA segment coding for the signal
      peptide of Escherichia coli ompF. E. coli cells harbouring an expression vector
      containing these genes downstream of a tac promoter were able to secrete a Fab
      fragment of the antibody efficiently. When the cells were cultured at 37 degrees
      C and the inducer (isopropyl-beta-D-thiogalactopyranoside, IPTG) concentration
      was 1 mM (standard conditions), production of functional Fab was very low
      (medium; 200 ng/l culture and periplasm; less than 90 ng/l culture). In order to
      optimize functional Fab production, we examined the influence of culture
      conditions (i.e. temperature and the inducer concentration) on secretion of the
      product. It was found that a 12.7-fold higher amount of Fab fragment could be
      produced at 30 degrees C using 0.1 mM IPTG, as compared with standard conditions.
      Under these optimal conditions, functional Fab accumulated in the periplasm and
      culture medium for 10 h after induction and the total production level was found
      to reach approximately 4.5 mg/l culture.

PMID- 1368907
TI  - Expression and secretion of pea-seed lipoxygenase isoenzymes in Saccharomyces
      cerevisiae.
AB  - Lipoxygenases (EC 1.13.11.12) catalyse the oxygenation of polyunsaturated fatty
      acids such as linoleic and arachidonic acid into reactive cis/trans
      hydroperoxidiene intermediates, which then serve as substrates for other enzymes
      leading to the production of a variety of secondary metabolites. In order to
      explore the characteristics of the individual lipoxygenase isoenzymes in more
      detail larger amounts of the pure enzymes are needed and their production in a
      heterologous host is therefore desirable. Full-length cDNAs encoding pea-seed
      lipoxygenase isoenzymes 2 and 3 were expressed in Saccharomyces cerevisiae with
      the aid of yeast-Escherichia coli shuttle vectors. Expression of the cDNA for
      lipoxygenase 2 under the control of the constitutive phosphoglycerate kinase
      (PGK) gene promoter yielded significant amounts of active enzyme inside the cell,
      both with yeast transformants carrying the cDNA gene on high-copy-number plasmids
      or integrated in chromosome V. Addition of the yeast invertase signal sequence in
      front of the pea lipoxygenase 3 yielded secreted active pea-seed lipoxygenase in
      the medium, but large amounts of inactive lipoxygenase 3 remained inside the
      yeast cell. Expression of the LOX3 cDNA can be achieved either constitutively
      with the PGK promoter or inducibly with the GAL1 promoter.

PMID- 1368910
TI  - Batch cultures of recombinant Lactococcus lactis subsp. lactis in a stirred
      fermentor. II. Plasmid transfer in mixed cultures.
AB  - The transfer of plasmids was studied in a stirred fermentor in the course of
      mixed batch cultures combining recombinant strains of Lactococcus lactis subsp.
      lactis (donor strains) with L. lactis subsp. lactis CNRZ 268M3 (recipient
      strain). Donor strains contained one or two of the following plasmids (coding for
      erythromycin or chloramphenicol resistance): pIL205 (self-transmissible), pIL252,
      pIL253 (non-transmissible but mobilizable by pIL205, respectively small and large
      copy number) and pE194 (inserted in the chromosome). Only self-transmissible
      plasmid pIL205 was transferred, with frequencies ranging from 10(-7) to 10(-8)
      after 12 h of fermentation. These frequencies were 60-400 times lower than in
      unstirred M17 broth and 100,000 times lower than on agar medium. In the latter
      case, non-transmissible plasmids pIL252 and pIL253 were mobilized by pIL205 with
      a frequency of about 10(-5) - 10(-6).

PMID- 1368909
TI  - Batch cultures of recombinant Lactococcus lactis subsp. lactis in a stirred
      fermentor. I. Effect of plasmid content on bacterial growth and on genetic
      stability in pure cultures.
AB  - The effect of plasmid introduction into Lactococcus lactis subsp. lactis IL2661
      on the growth of this strain and on plasmid stability was studied in pure batch
      cultures. The plasmids used (coding for erythromycin or chloramphenicol
      resistance) were the following: pIL205 (42 kb), pIL252 (4.6 kb, 6-9 copies),
      pIL253 (4.8 kb, 45-85 copies) and pE194 (inserted in the chromosome). Growth and
      acidification of L. lactis subsp. lactis IL2661 were similar to those of the
      derived recombinant lactococci. The maximal population at the end of the
      fermentation (9 h) was about 1.1 +/- 0.3 x 10(10) cfu/ml, and maximal growth rate
      0.92 +/- 0.07 h-1. Growth yield and lactic acid concentrations were 3.9 +/- 0.8 x
      10(11) cfu/g lactose consumed and 25.6 +/- 2.3 g/l, respectively. Different
      levels of plasmid stability were detected. Plasmid pE194, and plasmids pIL252 and
      pIL253 in the absence of pIL205, were stable after 10 h of culture. A slight loss
      (1-2%) of pIL205 was observed in all strains. In the presence of pIL205, plasmids
      pIL252 and pIL253 were maintained in only 56-95% of the cells. This result
      suggested an incompatibility between pIL205 and pIL252 or pIL253.

PMID- 1368911
TI  - Conjugative gene transfer in marine cyanobacteria: Synechococcus sp.,
      Synechocystis sp. and Pseudanabaena sp.
AB  - Versatility of gene transfer by transconjugation in marine cyanobacteria was
      demonstrated. In this study, seven different marine cyanobacteria were used as
      recipient cells. First, transconjugation was carried out using the mobilizable
      transposon (Tn5) carrying plasmid pSUP1021. Transconjugates were observed in all
      marine cyanobacteria tested. Second, the broad-host-range vector pKT0230 (IncQ)
      was tested for transconjugation. pKT230 has been successfully transferred in a
      marine cyanobacterium Synechococcus sp. NKBG15041C, and replicated as an
      autonomous replicon without alteration in the restriction enzyme pattern. A
      maximum transfer efficiency of 5.2 x 10(-4) transconjugants/recipient cell was
      observed, when mating was performed on agar plates containing low salinity (0.015
      M NaCl) medium. This is the first study to demonstrate gene transfer in marine
      cyanobacteria via transconjugation.

PMID- 1368912
TI  - Effect of ammonium ions on spiramycin biosynthesis in Streptomyces ambofaciens.
AB  - The effect of ammonium on growth and spiramycin biosynthesis in Streptomyces
      ambofaciens cultured on a chemically defined medium was studied. Spiramycin
      biosynthesis was better in the presence of valine and isoleucine than in the
      presence of ammonium. This production was reduced in the presence of excess
      ammonium (100 mM). The addition of catabolic intermediates of valine and
      isoleucine reserved the negative effect of ammonium. Valine dehydrogenase (VDH),
      the enzyme responsible for valine, leucine and isoleucine catabolism, was
      repressed when excess ammonium was present in the medium. This repression was
      approximately 25% when the ammonium concentration was increased from 50 to 100
      mM. In addition to the repression of VDH biosynthesis, ammonium inhibited the
      activity of this enzyme. This inhibition was 45 and 65% in the presence of 50 and
      100 mM ammonium, respectively.

PMID- 1368913
TI  - Transformation of N epsilon-CBZ-L-lysine to CBZ-L-oxylysine using L-amino acid
      oxidase from Providencia alcalifaciens and L-2-hydroxy-isocaproate dehydrogenase
      from Lactobacillus confusus.
AB  - Biotransformations were developed to oxidize N epsilon-carbobenzoxy(CBZ)-L-lysine
      and to reduce the product keto acid to L-CBZ-oxylysine. Lysyl oxidase (L-lysine:
      O2 oxidoreductase, EC 1.4.3.14) from Trichoderma viride was relatively specific
      for L-lysine and had very low activity with N epsilon-substituted derivatives. L
      Amino acid oxidase (L-amino acid: O2 oxidoreductase [deaminating], EC 1.4.3.2)
      from Crotalus adamanteus venom had low activity with L-lysine but high activity
      with N epsilon-formyl-, t-butyoxycarbonyl(BOC)-, acetyl-, trifluoroacetyl-, or
      CBZ-L-lysine. L-2-Hydroxyisocaproate dehydrogenase (EC 1.1.1.-) from
      Lactobacillus confusus catalyzed the reduction by NADH of the keto acids from N
      epsilon-acetyl-, trifluoroacetyl-, formyl- and CBZ-L-lysine but was inactive with
      the products from oxidation of L-lysine, L-lysine methyl ester, L-lysine ethyl
      ester or N epsilon-t-BOC-L-lysine. Providencia alcalifaciens (SC9036, ATCC 13159)
      was a good microbial substitute for the snake venom oxidase and also provided
      catalase (H2O2:H2O2 oxidoreductase EC 1.11.1.6). N epsilon-CBZ-L-Lysine was
      converted to CBZ-L-oxylysine in 95% yield with 98.5% optical purity by oxidation
      using P. alcalifaciens cells followed by reduction of the keto acid using L-2
      hydroxyisocaproate dehydrogenase. NADH was regenerated using formate
      dehydrogenase (formate: NAD oxidoreductase, EC 1.2.1.2) from Candida boidinii.
      The Providencia oxidase was localized in the particulate fraction and catalase
      activity was predominantly in the soluble fraction of sonicated cells. The pH
      optima and kinetic constants were determined for the reactions.

PMID- 1368914
TI  - Expression of high levels of human tissue plasminogen activator in yeast under
      the control of an inducible GAL promoter.
AB  - The human tissue plasminogen activator (h-tPA) cDNA was fused either with the
      leader sequence of the killer toxin of Kluyveromyces lactis or with the
      Saccharomyces diastaticus glucoamylase leader peptide and cloned in the yeast
      expression vector under the control of the inducible USAgal/CYC1 promoter. The
      recombinant tPA is produced in yeast as a single-chain glycosylated polypeptide
      of 66-72 kDa, which accumulates intracellularly associated with a membrane
      fraction. Using two-step fed-batch fermentation, a productivity up to 100 mg/l of
      active intracellular tPA was obtained.

PMID- 1368915
TI  - Studies on plasmid stability, cell metabolism and superoxide dismutase production
      by Pgk- strains of Saccharomyces cerevisiae.
AB  - A double mutant sod1/pgk1 strain of Saccharomyces cerevisiae has been constructed
      in order to investigate the effects of different environmental conditions on
      yeast physiology, plasmid stability, and superoxide dismutase (SOD) production.
      Strains were transformed with yeast episomal plasmids (YEp) containing both PGK1
      and SOD1 genes and were grown on fermentable carbon sources and under vigorous
      aeration. Under these conditions, the presence of the PGK1 gene was made
      essential for growth and both genes were efficiently expressed. However, plasmid
      borne PGK1 was found not to increase the stability of YEp vectors in batch
      cultures of Pgk- cells. Paradoxically, plasmid stability increased during the
      respiratory phase of growth. An investigation of the metabolism of Pgk- cells
      demonstrated that these glycolytic pathway mutants do not appreciably metabolize
      glycerol. Thus Pgk+, plasmid-containing, cells have a selective advantage during
      the respiratory phase of batch growth since they can utilize both glycerol and
      ethanol.

PMID- 1368916
TI  - In-vitro cleavage of a fusion protein bound to cellulose using the soluble yscFs
      (Kex2) variant.
AB  - In order to show site-specific cleavage of fusion proteins with an engineered
      soluble yscF variant, we have constructed a fusion gene encoding eglinC from
      Hirudo medicinalis and the cellulose-binding domain from the Cellulomonas fimi
      exoglucanase (Cex). The two fusion partners were separated by a Lys-Arg
      containing recognition sequence for the yeast endoprotease yscF (Kex2). The
      fusion protein (eglinC-Cex) was expressed intracellularly in Saccharomyces
      cerevisiae. After disruption of the cells eglin-C-Cex was shown to bind to
      cellulose when present in total crude cell lysates. This step efficiently removed
      the majority of contaminating host proteins. While immobilized on cellulose,
      eglin-C-Cex could be cleaved into the expected fragments. Upon cleavage the
      eglinC part was released from the cellulose, while the purification tag, i.e. the
      cellulose binding domain, stayed bound to the cellulose matrix.

PMID- 1368917
TI  - Elimination of by-products in 11 beta-hydroxylation of substance S using
      Curvularia lunata clones regenerated from NTG-treated protoplasts.
AB  - Stable mutants showing improved 11-hydroxylation of Substance S were isolated,
      following treatment with N-methyl-N'-nitro-N-nitrosoguanidine (NTG) and
      regeneration of uninucleate protoplasts of the appropriate fungal strains. This
      procedure was especially suitable for obtaining more directed 11 beta
      hydroxylation of Substance S with Curvularia lunata IM 2901. Apart from producing
      cortisol (11 beta-hydroxy-S), the parent strain formed several by-products that
      significantly lowered the yield of the desired 11 beta-hydroxyderivative.
      Isolated mutants of this microorganism carried out directed 11 beta-hydroxylation
      with only a small amount of one of the by-products, which resulted in a much
      higher yield of cortisol.

PMID- 1368918
TI  - Use of the polymerase chain reaction for specific detection of type A, D and E
      enterotoxigenic Staphylococcus aureus in foods.
AB  - By comparison with the DNA sequences coding for Staphylococcus aureus
      enterotoxins (ents) A, B, C, D and E, oligonucleotides unique to the entA, entD
      and entE genes were synthesized and used as polymerase-chain-reaction (PCR)
      primers for the specific detection of type A, D or E enterotoxigenic S. aureus.
      The relative molecular weights of the PCR products amplified with these primers
      were 210, 333 and 456 bp, respectively. Despite the high relatedness among these
      S. aureus enterotoxin genes, each primer pair allows specific detection with
      total discrimination from other types of enterotoxigenic S. aureus. DNA from non
      enterotoxigenic S. aureus or from non-S. aureus would not interfere with the PCR
      results either. Primers designed for entE detection allow the discrimination of
      entE strains that when assayed by a serological method might be classified as
      entA-producing strains. Study of the detection sensitivity showed that by using
      these primers, DNA from 10(0) cells of enterotoxigenic S. aureus could be
      detected unambiguously. When these oligonucleotide primers were used for the
      detection of S. aureus in foods, 10(0)-10(1) cells per gram of food could be
      detected and the naturally contaminating microflora in the food sample did not
      interfere with the detection.

PMID- 1368919
TI  - Object-oriented fuzzy expert system for on-line diagnosing and control of
      bioprocesses.
AB  - An object-oriented fuzzy expert system to support on-line control of an automated
      fermentation plant is described. The major elements of the system consist of a
      fuzzy inference engine, a database, a knowledge base, and an expression
      evaluater. The expression evaluater calculates specific rates for growth, and
      substrate and product formation at different physiological states during the
      cultivation from the measured data. The specific rates are then compared with the
      standard target rates stored in the database. If differences outside the set
      tolerances were observed, the inference engine analyses the reasons for the
      faults on the basis of the knowledge represented in the form of a knowledge
      network and fuzzy membership functions of the process variables. The fuzzy expert
      system was developed on the basis of a shell constructed by using the object
      oriented Smalltalk/V Mac programming environment, with Lac-tobacillus casei
      lactic acid fermentation as the example of process application.

PMID- 1368921
TI  - Legal notes.

PMID- 1368920
TI  - Secretion of genetically-engineered dihydrofolate reductase from Escherichia coli
      using an E. coli alpha-hemolysin membrane translocation system.
AB  - Secretion of fusion proteins composed of cytoplasmic protein dihydrofolate
      reductase (DHFR) and the Escherichia coli alpha-haemolysin (HlyA) C-terminal
      sequence was examined through the haemolysin secretion machinery of E. coli. DHFR
      of various lengths was combined with the HlyA C-terminal region, and both
      secretion and DHFR activity of the fusions were measured. The secretion was found
      to be inversely correlated with the intracellular DHFR activity. Moreover, when
      one amino acid (Ile155) in a beta-sheet of the DHFR C-terminal region was
      replaced with Lys, the enzymatically active DHFR fusion protein was secreted into
      the medium. We discuss the possibility of a relationship between folding and
      secretion of HlyA-fused protein in the HlyA secretion system.

PMID- 1368923
TI  - Education and training in biotechnology. Course commentaries around Australia &
      New Zealand. UNESCO training in Asia. Training Directory.

PMID- 1368922
TI  - Predicting the performance of chromatographic columns in protein purification
      processes.
AB  - The commercial success of chromatographic methods in large scale protein
      purification has created a strong demand for predictive techniques which will
      directly aid the design, scale-up and optimization of the process. This article
      examines the current state in the development of such techniques which depend for
      success not only on system analysis and modelling, but also on the collection of
      appropriate experimental data. A specific mathematical model describing non
      porous particle adsorption (NPPAM) developed by the authors, which is simple to
      use on readily available equipment, is outlined. Examples of using NPPAM for
      predicting column performance are given, as well as the potential of applying the
      model in process simulation and optimization.

PMID- 1368924
TI  - Australia's animal biotechnology companies.

PMID- 1368925
TI  - In vitro production of domestic animal embryos: advances made at Ruakura, New
      Zealand.

PMID- 1368926
TI  - Improved animal production by genetic engineering of ruminal bacteria.
AB  - Ruminant production is a major focus of Australian agriculture. The ability of
      ruminant animals such as sheep and cattle to make productive use of low quality
      plant materials depends on the activity and efficiency of the anaerobic microbial
      population that resides in the rumen. Factors that affect ruminant production
      include the ability of cellulolytic microorganisms to digest plant structural
      polysaccharides (primarily cellulose and hemicellulose), the capacity of
      microorganisms to metabolise and detoxify otherwise inhibitory plant products and
      the efficiency of nitrogen utilisation by ruminal organisms. This review will
      consider some current Australian research programs aimed at improving ruminant
      production efficiency by genetic engineering of ruminal bacteria.

PMID- 1368928
TI  - Draft planned release guidelines.

PMID- 1368927
TI  - Biotechnology in the diagnosis of animal diseases.

PMID- 1368929
TI  - The new product liability regime.

PMID- 1368930
TI  - Protein folding in vitro.
AB  - It is becoming increasingly evident that intermediates observed in protein
      folding in vitro may be closely related to conformational states that are
      important in various intracellular processes. This review focuses on recent
      advances in in vitro protein-folding studies with particular reference to the
      molten globule state, which is purported to be a common and distinct intermediate
      of protein folding.

PMID- 1368931
TI  - Folding and assembly of oligomeric proteins in Escherichia coli.
AB  - High levels of expression of oligomeric proteins in heterologous systems are
      frequently associated with misfolding and accumulation of the polypeptides in
      inclusion bodies. This reflects aspects of the folding and assembly pathways of
      oligomeric proteins, which generally proceed from either folding intermediates or
      native-like metastable species that are not in their final conformation. Methods
      for optimizing the yield of correctly assembled oligomers are discussed.

PMID- 1368932
TI  - Antibody expression in bacteriophage systems: the future of monoclonal
      antibodies?
AB  - Bacteriophage systems have been utilized to express and isolate antibodies. This
      promising technology has been evolving rapidly and has the potential to
      revolutionize the way in which monoclonal antibodies are generated. This review
      focuses on the many recent advances that have been made in obtaining monoclonal
      antibodies from bacteriophage systems.

PMID- 1368934
TI  - Engineering yeast for high level expression.
AB  - As a eukaryotic microbe, yeast remains an attractive host for the expression of a
      large variety of foreign proteins, including viral antigens, enzymes used as food
      additives and therapeutic agents. Important progress has been made in the
      understanding of the critical parameters influencing product yield, and a number
      of novel tools for the genetic engineering of powerful yeast expression systems
      have been developed. This review focuses on recent findings in foreign gene
      expression in the yeasts Saccharomyces, Pichia, Hansenula, and Kluyveromyces.

PMID- 1368933
TI  - Protein export in Escherichia coli.
AB  - The export of protein from Escherichia coli has been studied by genetic,
      biochemical and biophysical techniques. These studies have defined a number of
      steps in the export pathway and have identified the cellular components required
      for the translocation process. New information is presented on the function of
      some of these components.

PMID- 1368935
TI  - Inducible vectors for expression in mammalian cells.
AB  - The most recent developments in mammalian cell inducible expression systems have
      involved the use of bacterial gene control elements and viral transactivator
      proteins. The combination of hybrid viral transactivator and bacterial repressor
      proteins, and simple chemical inducers can provide induction ratios of over 1000
      fold. These developments will have applications in both cell-based research and
      the generation of transgenic animals.

PMID- 1368936
TI  - Internal translation initiation in the design of improved expression vectors.
AB  - The discovery of a novel, cap-independent mechanism of translation used by
      picornavirus mRNAs has led to new advances in the engineering of mammalian
      expression vectors. It is now possible to express several proteins in a
      coordinate fashion from a single mRNA. Improved expression vectors suitable for
      virus-mediated transfer and direct DNA transfer are described.

PMID- 1368937
TI  - Vaccinia and other poxvirus expression vectors.
AB  - Over the past year improvements have been made in recombinant vaccinia virus gene
      expression and a new method for inserting DNA into the poxvirus genome has been
      developed, along with alternative methods for selecting recombinant viruses.
      Attenuated and non-replicating vaccinia virus and avian poxvirus vectors are now
      being used successfully. Field trials of an oral, wild-life rabies vaccine and
      phase 1 testing of human vaccines derived from vaccinia virus are underway.

PMID- 1368938
TI  - Retroviral vectors for persistent expression in vivo.
AB  - Retroviral vectors provide a safe and efficient method of introducing genes of
      therapeutic interest into dividing cells. The principle limitation of these
      vectors in the past has been poor gene expression in vivo. This problem has been
      overcome recently through the use of tissue-specific enhancers in commonly used
      retroviral vectors. In this review we discuss both the relevant biology and some
      of the practical applications of retroviral vectors in gene therapy.

PMID- 1368939
TI  - Protein glycosylation.
AB  - Glycan structures can modulate the biological properties and functions of
      glycoproteins. This has been shown by investigation of the biological activities
      and glycan structures of several recombinant glycoproteins. Glycan structures of
      glycoproteins differ according to the species and tissue producing them, and
      selection of an appropriate host-cell type can generate recombinant glycoproteins
      with new characteristics.

PMID- 1368941
TI  - Expression systems.

PMID- 1368940
TI  - Protein processing within the secretory pathway.
AB  - Endoproteolytic cleavage of hormone and neuropeptide precursors, as well as many
      complex proteins, such as coagulation factors and viral glycoproteins, is a key
      process in the generation of bioactive polypeptides. These cleavages typically
      occur at the dibasic amino acid residues Lys-Arg or Arg-Arg. The enzymes
      responsible for the processing belong to a newly discovered family of serine
      proteases related to the bacterial subtilisins. These include PACE (furin),
      PC1/PC3, PC2 and PACE4, which have all been characterized functionally and
      structurally.

PMID- 1368942
TI  - Acceptor specificity of cyclodextrin glycosyltransferase from Bacillus
      stearothermophilus and synthesis of alpha-D-glucosyl O-beta-D-galactosyl-(1----4)
      beta-D-glucoside.
AB  - Bacillus stearothermophilus CGTase had a wider acceptor specificity than Bacillus
      macerans CGTase did and produced large amounts of transfer products of various
      acceptors such as D-galactose, D-mannose, D-fructose, D- and L-arabinose, D- and
      L-fucose, L-rhamnose, D-glucosamine, and lactose, which were inefficient
      acceptors for B. macerans CGTase. The main component of the smallest transfer
      products of lactose was assumed to be alpha-D-glucosyl O-beta-D-galactosyl-(1---
      4)-beta-D-glucoside.

PMID- 1368943
TI  - Characterization of D-aminoacylase from Alcaligenes denitrificans DA181.
AB  - The D-aminoacylase produced by Alcaligenes denitrificans DA181 was a new type of
      aminoacylase which had both high stereospecificity and specific activity. The
      molecular weight and isoelectric point of this enzyme were 58,000 and 4.4,
      respectively. The apparent Km and kcat values of this enzyme for N-acetyl-D
      methionine were estimated to be 0.48 mM and 6.24 x 10(4) min-1, respectively. The
      optimum temperature was 45 degrees C. The enzyme was stable up to 55 degrees C
      for 1 hr in the presence of 0.2 mg/ml bovine serum albumin. The enzyme was stable
      in the pH range of 6.0 to 11.0 with an optimum pH of 7.5. This enzyme contained
      about 2.1 g atom of zinc per mole of enzyme. Enzyme activity was inhibited by
      incubation with EDTA. The inhibition by EDTA was fully reversed by Co2+ and
      partially by Zn2+.

PMID- 1368944
TI  - Purification and properties of mycodextranase from Streptomyces sp. J-13-3.
AB  - An enzyme hydrolyzing nigeran (alternating alpha-1,3- and alpha-1,4-linked
      glucan) was purified from the culture filtrate of Streptomyces sp. J-13-3, which
      lysed the cell wall of Aspergillus niger, by percipitation with ammonium sulfate
      and column chromatographies on DEAE-Sephadex A-50, CM-Sephadex C-50,
      chromatofocusing, and Sephadex G-100. The final preparation was homogenous in
      polyacrylamide gel electrophoresis (PAGE). The molecular weight of the enzyme was
      68,000 by SDS-PAGE and gel filtration. The optimum pH and temperature for the
      enzyme activity were 6.0 and 50 degrees C, respectively. The enzyme was stable in
      the pH range from 6.0 to 8.0 and up to 50 degrees C. The enzyme activity was
      inhibited significantly by Hg+, Hg2+, and p-chloromercuribenzoic acid. The Km
      (mg/ml) for nigeran was 3.33. The enzyme specifically hydrolyzed nigeran into
      nigerose and nigeran tetrasaccharide by an endo-type of action, indicating it to
      be a mycodextranase (EC 3.2.1.61) that splits only the alpha-1,4-glucosidic
      linkages in nigeran.

PMID- 1368945
TI  - A novel and efficient method for enzymatic synthesis of high purity maltose using
      moranoline (1-deoxynojirimycin).
AB  - A transglycosylation reaction with moranoline (1-deoxynojirimycin) was done with
      soluble starch as the glucosyl donor and Bacillus macerans amylase as a
      cyclodextrin glycosyltransferase [EC 2.4.1.19]. The resultant transglycosylation
      products with moranoline, obtained by treating the reaction mixture with a strong
      cation exchange resin, were hydrolyzed by beta-amylase [EC 3.2.1.2] from sweet
      potatoes. The hydrolysate was treated with a strong cation exchange resin, and
      high purity maltose was obtained.

PMID- 1368946
TI  - Purification of acetyl coenzyme A: deacetylacephalosporin C O-acetyltransferase
      from Acremonium chrysogenum.
AB  - Acetyl CoA: deacetylcephalosporin C O-acetyltransferase, which catalyzes the
      final step of the biosynthetic pathway to cephalosporin C, was stabilized by a
      buffer solution containing 7-aminocephalosporanic acid and purified over 1300
      fold from Acremonium chrysogenum. The purified enzyme has a molecular weight of
      55,000 as measured by gel filtration. SDS-polyacrylamide gel electrophoresis
      showed two subunit bands corresponding to molecular weights of 27,000 and 14,000.
      The enzyme has an isoelectoric point at pH 4.0 and optimum activity at pH 7.5.

PMID- 1368947
TI  - Regioselectivity in sulfation of galactosides by sulfuric acid and
      dicyclohexylcarbodiimide.
AB  - Methyl alpha- and beta-D-galactopyranosides and 4-O-beta-D-galactopyranosyl-3,6
      anhydro-L-galactose dimethylacetal were sulfated with sulfuric acid and
      dicyclohexylcarbodiimide as a condensation reagent. The sulfated sugars were
      isolated by ion-exchange chromatography, characterized, and assigned by
      methylation analyses. On the basis of the yield of each sulfated product that was
      isolated, sulfation on O-6 appeared to be predominant.

PMID- 1368948
TI  - Effects of alpha-tocopherol and tocotrienols on blood pressure and linoleic acid
      metabolism in the spontaneously hypertensive rat (SHR).
AB  - Both alpha-tocopherol and a 1:1.7 mixture of alpha-tocopherol and tocotrienols at
      a 0.2% dietary level significantly depressed the age-related increase in the
      systolic blood pressure of spontaneously hypertensive rats (SHRs) after 3 weeks
      of feeding. The aortic production of prostacyclin was increased 1.5 times both by
      alpha-tocopherol and a tocotrienol mixture, suggesting a possible relevance to
      their hypotensive effect. These vitamins did not influence the delta 6- and delta
      5-desaturase activities of liver microsomes, but fatty acid profiles of the liver
      phospholipids predicted a reduction of linoleic acid desaturation. These effects
      were in general more clear with tocotrienols than with alpha-tocopherol. Platelet
      aggregation by 5 microM ADP remained uninfluenced. Thus, tocotrienols may have
      effects on various lipid parameters somewhat different from those of alpha
      tocopherol.

PMID- 1368949
TI  - Structural and functional properties of hen egg-white lysozyme deamidated by
      protein engineering.
AB  - The structural and functional properties of lysozymes genetically deamidated at
      positions 103 (N103D) and 106 (N106D) were studied by a protein engineering
      technique. The wild-type and mutant lysozymes were expressed in Saccharomyces
      cerevisiae and purified from the cultivation medium in two steps by cation
      exchange chromatography on CM-Toyopearl. The lytic activity of deamidated
      lysozymes was almost the same as that of wild lysozyme, although the optimal pH
      of activity was slightly shifted to lower pH by the deamidation. The Gibbs free
      energy changes of unfolding (delta G) at 20 degrees C for N103D and N106D were
      almost the same as that of wild-type. On the other hand, the structural
      flexibility of lysozymes, estimated by protease digestion, was significantly
      increased by the deamidation. The surface functional properties of deamidated
      lysozymes were considerably enhanced, compared to those of wild-type lysozyme.
      These results suggest that structural flexibility is an important governing
      factor in surface functional properties of proteins, regardless of their
      structural stability.

PMID- 1368950
TI  - Effects of Bacillus thuringiensis var. israelensis 20-kDa protein on production
      of the Bti 130-kDa crystal protein in Escherichia coli.
AB  - A 20-kDa protein of Bacillus thuringiensis var. israelensis (Bti) has been shown
      to be necessary for the efficient expression of the 27-kDa mosquitocidal protein
      gene in Escherichia coli. We have investigated the effects of this 20-kDa protein
      on the expression of two 130-kDa mosquitocidal protein genes (cryIVA, cryIVB) in
      E. coli by supplying the 20-kDa protein gene in trans. When a recombinant
      plasmid, pLH4BX, which was constructed to express cryIVA under the E. coli lac
      promoter on pUC19, coexisted with the 20-kDa protein gene, a striking increase in
      production of the fused CryIVA was detected. This was not accompanied by an
      increase in the amount of intracellular mRNA, suggesting that 20-kDa protein
      exerts a posttranscriptional effect. We conclude that the 20-kDa protein also
      stimulates the production of 130-kDa protein in E. coli.

PMID- 1368951
TI  - T1801 A, B, C, and D, new quinone and hydroquinone antibiotics produced by a
      strain of Pseudomonas.
AB  - New antibiotics, T1801 A, B, C, and D, were isolated from the culture broth of
      Pseudomonas sp. SC-1801. Their structures were found by spectroscopic analyses to
      be tri- and tetra(methylthio) derivatives of hydroquinone (T1801 A and C) or p
      benzoquinone (T1801 B and D). They are new quinone and hydroquinone antibiotics
      and are active against Gram-positive bacteria, some fungi, and yeasts.

PMID- 1368952
TI  - Molecular cloning, nucleotide sequence, and expression of the structural gene for
      alkaline serine protease from alkaliphilic Bacillus sp. 221.
AB  - The gene encoding an alkaline serine protease from alkaliphilic Bacillus sp. 221
      was cloned in Escherichia coli and expressed in Bacillus subtilis. An open
      reading frame of 1,140 bases, identified as the protease gene was preceded by a
      putative Shine-Dalgarno sequence (AGGAGG) with a spacing of 7 bases. The deduced
      amino acid sequence had a pre-pro-peptide of 111 residues followed by the mature
      protease comprising 269 residues. The alkaline protease from alkaliphilic
      Bacillus sp. 221 had higher homology to the protease from alkaliphilic bacilli
      (82.1% and 99.6%) than to those from neutrophilic bacilli (60.6-61.7%). Also
      Bacillus sp. 221 protease and other protease from alkaliphilic bacilli shared
      common amino acid changes and 4 amino acid deletions that seemed to be related to
      characteristics of the enzyme of alkaliphilic bacilli when compared to the
      proteases from neutrophilic bacilli.

PMID- 1368954
TI  - A modified colorimetric MTT assay adapted for primary cultured hepatocytes:
      application to proliferation and cytotoxicity assays.

PMID- 1368953
TI  - Stimulation of interferon beta production of cultured cells by phospholipids in
      foodstuffs.

PMID- 1368955
TI  - Facile synthesis of methyl 2-O-alpha-L-rhamnopyranosyl-alpha-L-rhamnopyranoside
      and methyl 2-O-alpha-L-mannopyranosyl-alpha-L-rhamnopyranoside.

PMID- 1368956
TI  - A novel in vivo screening method for immunomodulating substances: development of
      an assay system.

PMID- 1368957
TI  - Transformation of a Leu- mutant of Rhizopus niveus with the leuA gene of Mucor
      circinelloides.

PMID- 1368958
TI  - Ultra-rapid transformation of Escherichia coli by an alkali cation.

PMID- 1368959
TI  - Large-scale production of membrane proteins fused to a truncated SecA in
      Escherichia coli.

PMID- 1368960
TI  - Bacterial degradation of 3-chloroacrylic acid and the characterization of cis-
      and trans-specific dehalogenases.
AB  - A coryneform bacterium that is able to utilize cis- and trans-3-chloroacrylic
      acid as sole carbon source for growth was isolated from freshwater sediment. The
      organism was found to produce two inducible dehalogenases, one specific for the
      cis- and the other for trans-3-chloroacrylic acid. Both dehalogenases were
      purified to homogeneity from cells induced for dehalogenase synthesis with 3
      chlorocrotonic acid. The enzymes produced muconic acid semialdehyde (3
      oxopropionic acid) from their respective 3-chloroacrylic acid substrate. No other
      substrates were found. The cis-3-chloroacrylic acid dehalogenase consisted of two
      polypeptide chains of a molecular weight 16.2 kDa. Trans-3-chloroacrylic acid
      dehalogenase was a protein with subunits of 7.4 and 8.7 kDa. The subunit and
      amino acid compositions and the N-terminal amino acid sequences of the enzymes
      indicate that they are not closely related.

PMID- 1368961
TI  - Toxicity of chlorobenzene on Pseudomonas sp. strain RHO1, a chlorobenzene
      degrading strain.
AB  - Pseudomonas sp. strain RHO1 able to use chloro- and 1,4-dichlorobenzene as growth
      substrates was tested towards sensitivity against chlorobenzene. Concentrations
      of chlorobenzene higher than 3.5 mM were found to be toxic to cells independent
      of pregrowth with chlorobenzene or nutrient broth. Below this concentration,
      sensitivity towards chlorobenzene depended on the precultivation of the cells,
      i.e. type of growth substrate (chlorobenzene or nutrient broth) and the
      concentration of chlorobenzene as the growth substrate. Cells grown in continuous
      culture were especially sensitive with a threshold concentration of 2.5 mM
      chlorobenzene. In addition to chlorobenzene, metabolites also seem to function as
      toxic compounds. 2-Chlorophenol and 3-chlorocatechol were isolated from cell
      extracts. Cleavage of 3-chlorocatechol by catechol 1,2-dioxygenase seems to be
      the critical step in the metabolism of chlorobenzene.

PMID- 1368962
TI  - Biodegradation and sorption properties of polydisperse acrylate polymers.
AB  - Polyacrylate (PA), which is widely used in disposable diapers, is synthesized by
      polymerization and cross-linking of acrylate. During the synthesis, 3-6% of the
      polyacrylate polymers is not incorporated into the absorbent material, but
      remains soluble. If the soluble PA is mobilized from a landfill, it could enter
      the groundwater. Therefore, the biodegradation and adsorption properties of
      soluble polymers contained in PA are determined in this study. The soluble PA is
      highly polydisperse, and the fraction tested has a weight-average molecular
      weight of 16,700 and a range extending from 10(3) to 10(5). Sand-column tracer
      tests show that about 1% of the polyacrylate is unadsorbed, but the remainder has
      a retardation factor that averages at least 58. Biodegradation kinetics are
      determined in completely mixed biofilm reactors having a methanogenic consortium
      grown on glucose. The polyacrylate fraction, as well as glucose and acrylate, are
      removed and mineralized to CO2. The Monod parameters for the polyacrylate are:
      maximum specific rate of substrate utilization = 0.0016 gC/g biomass-day, and
      half-maximum-rate concentration = 0.79 gC/m3. Although these kinetics are much
      slower than for glucose and acrylate, significant degradation and mineralization
      are observed.

PMID- 1368963
TI  - Degradation and dehalogenation of monochlorophenols by the phenol-assimilating
      yeast Candida maltosa.
AB  - The phenol-assimilating yeast Candida maltosa is able to degrade
      monochlorophenols but cannot grow on these substrates. 3- and 4-chlorophenol were
      broken down very rapidly by phenol-grown cells under the formation of 4
      chlorocatechol, 5-chloropyrogallol and 4-carboxymethylenebut-2-en-4-olide with
      concomitant release of chloride. 2-Chlorophenol was partially converted into
      cis,cis-2-chloromuconic acid via 3-chlorocatechol which was also obtained from 3
      chlorophenol in low amounts. No further metabolites containing chloride were
      found. The dehalogenation step in the chlorophenol degradation is the
      cycloisomerization of the cis,cis-chloromuconic acid to 4-carboxymethylenebut-2
      en-4-olide in the ortho fission pathway.

PMID- 1368965
TI  - Cross-reactivity of bacteriocins from lactic acid bacteria and lantibiotics in a
      nisin bioassay and ELISA.
AB  - A number of bacteriocins from lactic acid bacteria and lantibiotics were tested
      for cross-reactivity in a nisin ELISA and bioassay. The bacteriocins showed no
      cross-reactivity, reflecting their structural dissimilarity from nisin. The
      lantibiotic subtilin which shares many common structural features with nisin,
      showed a high cross-reactivity in both the ELISA and the bioassay suggesting
      possible modifications to nisin to enhance its activity. Gallidermin did not
      cross react in the ELISA but did produce a zone of inhibition in the less
      specific bioassay. Other lantibiotics tested did not react in either assay.

PMID- 1368964
TI  - Degradation of polychlorinated phenols by Streptomyces rochei 303.
AB  - The strain Streptomyces rochei 303 (VKM Ac-1284D) is capable of utilizing 2
      chloro-, 2,4-, 2,6-dichloro- and 2,4,6-trichlorophenols as the sole source of
      carbon. Its resting cells completely dechlorinated and degraded 2-, 3-chloro-;
      2,4-, 2,6-, 2,3-, 2,5-, 3,4-, 3,5-dichloro-; 2,4-, 2,6-dibromo-; 2,4,6-, 2,4,5-,
      2,3,4-, 2,3,5-, 2,3,6-trichlorophenols; 2,3,5,6-tetrachloro- and
      pentachlorophenol. During chlorophenol degradation, a stoichiometric amount of
      chloride ions was released and chlorohydroquinols were formed as intermediates.
      In cell-free extracts of S. rochei, the activity of hydroxyquinol 1,2-dioxygenase
      was found. The enzyme was induced with chlorophenols. Of all so far described
      strains degrading polychlorophenols, S. rochei 303 utilized a wider range of
      chlorinated phenols as the sole sourse of carbon and energy.

PMID- 1368966
TI  - Hydroxypropyl cellulose/poly(ethylene glycol)-co-poly(propylene glycol) aqueous
      two-phase systems: system characterization and partition of cells and proteins.
AB  - Novel aqueous polymeric two-phase systems are described. These systems are formed
      by mixing hydroxypropyl cellulose (molecular mass 100,000, trade name Klucel L)
      with poly(ethylene glycol)-co-poly(propylene glycol) copolymer [molecular mass
      6,500, poly(propylene glycol) content 50% w/w, trade name Pluronic P105], in a
      saline buffer. The phase diagram was measured and the interfacial tensions, phase
      separation times, and lower phase viscosities of three phase systems having
      constant Pluronic P105 concentration but varying in Klucel L concentration were
      determined. The partition behavior of a representative cell, bacterium, and
      protein and the affinity ligand-mediated alteration in the partition behavior of
      a protein from a yeast extract protein mixture were also characterized. The
      results suggest that Klucel L/Pluronic P105 phase systems may be cost-effective
      substitutes for, or complements to, existing aqueous polymeric phase systems. The
      physical characterization and representative partition data reported here should
      facilitate application of these new systems.

PMID- 1368967
TI  - Strategies for enzymatic esterification in organic solvents: comparison of
      microaqueous, biphasic, and micellar systems.
AB  - The kinetics of butyl butyrate synthesis by a lipase from Mucor miehei in
      different types of organic media were investigated. The three systems studied
      were a microaqueous medium containing enzyme in suspension in hexane, a water
      hexane two-phase system, and reverse micelles. The synthesis of butyl butyrate
      was possible in all cases because of a favorable partition of the ester into the
      organic solvent. A sufficient stirring rate was necessary to achieve good
      reaction rates in the case of the liquid-liquid biphasic medium. The effect of
      water content was different according to the type of system used. The dependence
      of reaction rate and of conversion yield on enzyme and substrate concentrations
      was also investigated. From an applied point of view, the best performances were
      obtained with either microaqueous or liquid-liquid two-phase systems. The use of
      reverse micelles can be advocated only in particular conditions, such as low
      enzyme concentration, compatible with the specific constraints it involves.

PMID- 1368968
TI  - Ceramic membrane microfilter as an immobilized enzyme reactor.
AB  - This study investigated the use of a ceramic microfilter as an immobilized enzyme
      reactor. In this type of reactor, the substrate solution permeates the ceramic
      membrane and reacts with an enzyme that has been immobilized within its porous
      interior. The objective of this study was to examine the effect of permeation
      rate on the observed kinetic parameters for the immobilized enzyme in order to
      assess possible mass transfer influences or shear effects. Kinetic parameters
      were found to be independent of flow rate for immobilized penicillinase and
      lactate dehydrogenase. Therefore, neither mass transfer nor shear effects were
      observed for enzymes immobilized within the ceramic membrane. Both the residence
      time and the conversion in the microfilter reactor could be controlled simply by
      regulating the transmembrane pressure drop. This study suggests that a ceramic
      microfilter reactor can be a desirable alternative to a packed bed of porous
      particles, especially when an immobilized enzyme has high activity and a low
      Michaelis constant.

PMID- 1368969
TI  - Labeled proteinase inhibitors: versatile tools for the characterization of serine
      proteinases in solid-phase assays.
AB  - Peptidyl chloromethyl ketones were used for the specific labeling of proteinases
      by attaching a biotin group to the N-terminal end of the peptide. Such labeled
      peptide inhibitors allowed the detection and quantitation of proteolytic enzymes
      immobilized on the plastic surface of a microtiter plate, as well as on
      nitrocellulose. The validity of these solid-phase assays was demonstrated using
      subtilisin Carlsberg as a model enzyme and biotinyl-epsilon-aminocaproyl-L-alanyl
      L-alanyl-L-propyl-L-phenylal++  + anyl- chloromethyl ketone as a specific
      reagent. In addition to being usable for the screening of a particular proteinase
      in a large number of samples, these assays can be adapted for the analysis of
      specific proteolytic enzyme present in complex mixtures.

PMID- 1368970
TI  - Peptide synthesis by proteases in organic solvents: medium effect on substrate
      specificity.
AB  - The substrate specificities of alpha-chymotrypsin and subtilisins for peptide
      synthesis in hydrophilic organic solvents were investigated. Chymotrypsin
      exhibited high specificity to aromatic amino acids as acyl donors, while
      subtilisin Carlsberg and subtilisin BPN' were specific to aromatic and neutral
      aliphatic amino acids, in accordance with the S1 specificities of the enzymes for
      peptide hydrolysis in aqueous solutions. On the contrary, chymotrypsin exhibited
      higher specificities to hydrophilic amino acid amides as acyl acceptors
      (nucleophiles) for peptide synthesis with N-acetyl-L-tyrosine ethyl ester, in
      contrast to the S1' specificity for peptide hydrolysis and peptide synthesis in
      aqueous solutions. Furthermore, nucleophile specificity changed with the change
      in water-organic solvent composition; the increase in water content led to
      increase in relative reactivity of leucinamide to that of alaninamide. It was
      also found that protection of the carboxyl group of alanine by amidation is much
      preferable to protection by esterification in terms of reactivity as
      nucleophiles.

PMID- 1368971
TI  - Influence of dissolved oxygen concentration on the biosynthesis of cephalosporin
      C.
AB  - Cephalosporin C was produced by a highly productive strain of Cephalosporium
      acremonium under industrial production conditions by fed-batch cultivation in a
      40-l stirred-tank reactor using a complex medium containing 50 g l-1 peanut
      flour. The influence of dissolved oxygen concentration (pO2, DOC), which was
      maintained at different constant levels between 5 and 40% of its saturation
      value, during the production phase by means of a parameter-adaptive pO2
      controller, on the cephalosporin C biosynthesis, was investigated. The
      concentrations of cephalosporin C (CPC) and its precursors penicillin N (PEN N),
      deacetoxycephalosporin C (DAOC), and deacetylcephalosporin C (DAC) were monitored
      by on-line HPLC. The concentrations of amino acids, valine (VAL), cysteine (CYS),
      alpha-amino-adipic acid (alpha-AAA), the dipeptide alpha-amino-adipyl-cysteine
      (AC), and the tripeptide alpha-amino-adipyl-cysteinyl-valine (ACV) were
      determined by off-line HPLC. By reducing the pO2 in the production phase from 40
      to 5% of its saturation value, the CPC concentration diminished from 7.2 to 1.1 g
      l-1 and the PEN N concentration increased from 2.57 to 7.65 g l-1. The DAC
      concentration also dropped from 3.13 to 0.42 g l-1; however, the DAOC
      concentration was less influenced. The concentrations of AC and ACV were also
      less affected. The small DOC did not lead to an accumulation of the intermediate
      AC and ACV during the production phase. With increasing DOC in the range of 5
      20%, the maximal specific production rate, the cell mass concentration-based and
      the substrate-based yield coefficients for CPC increased almost linearly, and
      fell back for PEN N.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1368972
TI  - Bioconversion of naturally occurring precursors and related synthetic compounds
      using plant cell cultures.
AB  - The nearly unlimited enzymatic potential of cultured plant cells can basically be
      employed for bioconversion purposes. Plant enzymes are able to catalyze regio-
      and stereospecific reactions and can therefore be applied to the production of
      compounds of pharmaceutical interest. Naturally occurring as well as related
      synthetic compounds may be used as precursors. A review of the current status of
      such bioconversions is given. It includes the performance of bioconversions by
      freely suspended and immobilized plant cells or enzyme preparations. In addition,
      the kinetic aspects of immobilized plant cells are discussed. Special attention
      is paid to the bioconversion of poorly or water insoluble precursors. Finally, a
      model scheme for the development of a commercially available drug, produced by
      bioconversion, and perspectives are discussed.

PMID- 1368973
TI  - Problems of optimisation of plant cell culture processes.
AB  - The adoption of plant cell cultures as an industrial process depends greatly on
      the economics of such a process. The multicycle or draw-fill culture technique is
      one method for improving the productivity and, hence, cost of a process.
      Mathematical models have been devised for the functional relationships between
      the nominal costs of biomass and secondary metabolites and the plant cell growth
      characteristics in a multicycle growth system. The models were used to evaluate
      the data obtained with cultures of Dioscorea deltoidea (which produces diosgenin)
      and Panax ginseng, grown in various types of bioreactors. The multicycle system
      gave an increase of 1.5-2 in biomass productivity compared with batch culture,
      but was probably only commercially viable if the cost of the process in the
      bioreactor was at least 30 times that of the medium and if an inoculum of about
      30% of the culture of the previous cycle was left in the bioreactor. In the
      multicycle system incompletely utilised nutrient or metabolite accumulation can
      only reach 1.43 times or less that of the initial values. With the P. ginseng
      culture, about 75% of the calculated maximum cell packing density per fresh
      weight (approximately 530 g 1-1) in this regime was achieved. The possibility of
      growth in the standard bioreactor of a shear sensitive type culture was shown
      with a marine impeller speed up to 330 cm s-1.

PMID- 1368974
TI  - Effects of glycerol on the growth, adhesion, and cellulolytic activity of rumen
      cellulolytic bacteria and anaerobic fungi.
AB  - The effect of glycerol on the growth, adhesion, and cellulolytic activity of two
      rumen cellulolytic bacterial species, Ruminococcus flavefaciens and Fibrobacter
      succinogenes subsp. succinogenes, and of an anaerobic fungal species,
      Neocallimastix frontalis, was studied. At low concentrations (0.1-1%), glycerol
      had no effect on the growth, adhesion, and cellulolytic activity of the two
      bacterial species. However, at a concentration of 5%, it greatly inhibited their
      growth and cellulolytic activity. Glycerol did not affect the adhesion of
      bacteria to cellulose. The growth and cellulolytic activity of N. frontalis were
      inhibited by glycerol, increasingly so at higher concentrations. At a
      concentration of 5%, glycerol totally inhibited the cellulolytic activity of the
      fungus. Thus, glycerol can be added to animal feed at low concentrations.

PMID- 1368975
TI  - Mycobacterial growth and ultrastructure in mouse L-929 fibroblasts and bone
      marrow-derived macrophages: evidence that infected fibroblasts secrete mediators
      capable of modulating bacterial growth in macrophages.
AB  - The intracellular growth kinetics of Mycobacterium avium and H37Rv (virulent) and
      H37Ra (avirulent) strains of Mycobacterium tuberculosis were compared by use of
      both the professional (mouse bone marrow-derived macrophages, BMM phi) and
      nonprofessional (mouse L-929 fibroblast cell line) phagocytes. The results
      obtained showed that all the mycobacterial strains grew more actively in
      fibroblasts than in BMM phi. This difference was paralleled by lesser acid
      phosphatase (AcP) labeling of noninfected fibroblasts and the observation that
      upon infection both the proportion of AcP-positive cells and AcP content were
      higher in BMM phi than in L-cells during the 7 days of infection. In parallel
      experiments, intracellular growth of M. tuberculosis H37Rv and M. avium was
      compared inside BMM phi from both the Bcgs (C57BL/6) and Bcgr (DBA-2) mice, which
      were matured and differentiated with either an L-cell-conditioned medium (LCM)
      obtained from control, noninfected L-929 cells, or a LCM obtained with M.
      tuberculosis- or M. avium-infected L-cells. Upon mycobacterial infection,
      fibroblasts were able to secrete mediators that stimulated the BMM phi to better
      control the infection by pathogenic mycobacteria. These results are discussed in
      terms of the mycobacteria-fibroblast interactions and their eventual role in the
      immune modulation of the host's response to invading mycobacteria.

PMID- 1368976
TI  - Trinitrotoluene (TNT) as a sole nitrogen source for a sulfate-reducing bacterium
      Desulfovibrio sp. (B strain) isolated from an anaerobic digester.
AB  - A sulfate-reducing bacterium (SRB), Desulfovibrio sp. (B strain), isolated from a
      continuous anaerobic digester (Boopathy and Daniels, Current Microbiology, 23:327
      332, 1991) was found to use 2,4,6-trinitrotoluene (TNT) as sole nitrogen source.
      This bacterium also used nitrate, nitrite, and ammonium as nitrogen source. A
      long lag period was noticed when TNT or nitrite was used as nitrogen source.
      Nitrate, nitrite and TNT also served as electron acceptor in the absence of
      sulfate for this bacterium. Under nitrogen-limiting condition, 100% removal of
      TNT was observed within 8 days of incubation. The main intermediate observed was
      diaminonitrotoluene, which was further converted to toluene via triaminotoluene
      by reductive deamination process. Under nitrogen-rich conditions (presence of
      ammonium), TNT was converted to diaminonitrotoluene, and toluene was not
      produced. This isolate did not degrade TNT all the way to CO2. This study
      demonstrated the possibility of using this isolate to decontaminate the soil and
      water contaminated with TNT under anaerobic conditions.

PMID- 1368977
TI  - Saponins from Verbascum nigrum.
AB  - Two triterpene saponins have been isolated from the inflorescences of Verbascum
      nigrum. Their structures were determined by chemical and spectral methods as 3-O
      ([alpha-L-rhamnosyl-(1-->4)-(beta-D-glucopyranosyl-(1-->3)]-be ta-D
      glucopyranosyl]-(1-->2)-beta-fucopyranosyl)-13 beta,28-epoxyolean-11-ene-3
      beta,23-diol and 3-O-([alpha-L-rhamnosyl-(1-->4)-(beta-D-glucopyranosyl-(1-->3)
      bet a-D- glucopyranosyl]-(1-->2)-beta-fucopyranosyl)-11-methoxy-olean-12-en e-3
      beta,23,28-triol.

PMID- 1368978
TI  - 3-D biotech: tissue engineering.

PMID- 1368979
TI  - Whole animals for wholesale protein production.

PMID- 1368980
TI  - An appetite for technology: Hoffmann-La Roche.

PMID- 1368981
TI  - Up to code: validating a chromatography system.

PMID- 1368982
TI  - The art of social bioengineering.

PMID- 1368983
TI  - Use of the nirB promoter to direct the stable expression of heterologous antigens
      in Salmonella oral vaccine strains: development of a single-dose oral tetanus
      vaccine.
AB  - Plasmid pTETnir15, which directs the expression of the non-toxic immunogenic
      fragment C of tetanus toxin from the anaerobically inducible nirB promoter, was
      introduced into the Salmonella typhimurium aroA aroD live oral vaccine strain
      BRD509. The resulting strain, designated BRD847, was used to vaccinate orally
      BALB/c mice and was tested for plasmid stability and its ability to protect
      against a lethal tetanus toxin challenge. pTETnir15 was stably inherited by
      bacteria growing or persisting in the tissues of immunized mice whereas another
      BRD509 derivative, designated BRD753, harboring plasmid pTET85 which directs
      fragment C expression from the tac promoter, was highly unstable. Mice immunized
      with a single oral dose of BRD847 developed high levels of circulating anti
      fragment C antibodies and were solidly protected against tetanus toxin challenge.
      Mice immunized with a single oral dose of BRD753 developed no detectable anti
      fragment C antibodies. After boosting, antibodies were detected, but the mice
      were only partially protected against tetanus toxin challenge. Thus the use of an
      in vivo inducible promoter such as nirB may be a generally applicable approach to
      obtaining the stable in vivo expression of heterologous antigens in Salmonella
      vaccine strains.

PMID- 1368984
TI  - Metabolic engineering of Candida tropicalis for the production of long-chain
      dicarboxylic acids.
AB  - We have engineered an industrial strain of the yeast, Candida tropicalis, for the
      efficient production of long-chain dicarboxylic acids, which are important raw
      materials for the chemical industry. By sequential disruption of the four genes
      encoding both isozymes of the acyl-CoA oxidase which catalyzes the first reaction
      in the beta-oxidation pathway, alkane and fatty acid substrates have been
      successfully redirected to the omega-oxidation pathway. Consequently, the
      conversion efficiency and chemical selectivity of their terminal oxidation to the
      corresponding dicarboxylic acids has been improved to 100 percent. The specific
      productivity of the bioconversion has been increased further by amplification of
      the cytochrome P450 monooxygenase and NADPH-cytochrome reductase genes encoding
      the rate-limiting omega-hydroxylase in the omega-oxidation pathway. The amplified
      strains demonstrated increased omega-hydroxylase activity and a 30% increase in
      productivity compared to the beta-oxidation-blocked strain in fermentations. The
      bioconversion is effective for the selective terminal oxidation of both saturated
      and unsaturated linear aliphatic substrates with chain-lengths ranging from 12
      carbons to 22 carbons and also avoids the undesirable chain modifications
      associated with passage through the beta-oxidation pathway, such as unsaturation,
      hydroxylation, or chain shortening. It is now possible to efficiently produce a
      wide range of previously unavailable saturated and unsaturated dicarboxylic acids
      with a high degree of purity.

PMID- 1368985
TI  - A universal expression-purification system based on the coiled-coil interaction
      of myosin heavy chain.
AB  - We have constructed a series of Escherichia coli expression vectors that produce
      high yields of fusion proteins containing the C-terminal fragment of light
      meromyosin (LMM) from rabbit fast skeletal muscle. The fusion proteins retain the
      ability of LMM to form polymers in low salt and to be soluble in high salt. Thus
      they can be easily purified from bacterial extracts with a high salt-low salt
      extraction procedure and still retain their biochemical properties. We
      demonstrate the utility of this system for the heterologous production and simple
      purification of LMM fusions of p21H-ras, the neurofibromatosis type I protein and
      the Tat and protease proteins of HIV-1.

PMID- 1368986
TI  - Expression of a bacterial phaseolotoxin-resistant ornithyl transcarbamylase in
      transgenic tobacco confers resistance to Pseudomonas syringae pv. phaseolicola.
AB  - Toxins have been shown to be an important virulence component for most pathovars
      of Pseudomonas syringae. Here we have examined the role of phaseolotoxin in the
      virulence mechanism of P. syringae pv. phaseolicola by producing transgenic
      tobacco plants that express a pathogen-derived toxin-resistant target enzyme.
      Such plants are insensitive to the toxin and less prone to infection by the
      pathogen.

PMID- 1368987
TI  - Antibody production in silkworm cells and silkworm larvae infected with a dual
      recombinant Bombyx mori nuclear polyhedrosis virus.
AB  - We have examined the efficiency of coexpression of two heterologous genes from a
      recombinant Bombyx mori nuclear polyhedrosis virus for the production of
      antibodies in silkworm larvae. The cDNAs encoding the light and the heavy chains
      of a murine immunoglobulin, directed against lipoprotein I of Pseudomonas
      aeruginosa, were brought under the control of two separate copies of the viral
      polyhedrin promotor. Infection of silkworm cells with the recombinant baculovirus
      yielded a maximum of 6.4 micrograms/ml IgG2A in the culture supernatant 72 hours
      post infection, while 800 micrograms/ml IgG2A was found in the hemolymph of
      infected fifth instar silkworm larvae seven days after infection with the same
      construct. The recombinant antibody exhibited a similar antigen specificity and
      avidity to that of the monoclonal antibody derived from ascites fluid.

PMID- 1368988
TI  - Chemical crosslinking and the stabilization of proteins and enzymes.
AB  - The technique of chemical crosslinking has been used to enhance the stability of
      proteins and enzymes. In this procedure, the molecule is braced with chemical
      crosslinks either intramolecularly or intermolecularly to another species to
      reinforce its active structure. Various chemicals have been used for this
      purpose. The bifunctional reagents are the most prominent. These compounds are
      derived from group-specific reagents and may be classified into homobifunctional,
      heterobifunctional, and zero-length crosslinkers. Different physical and chemical
      characteristics have been incorporated into these chemicals. Their versatility
      holds great potential in preparing chemically, thermally, and mechanically stable
      proteins and enzymes for industrial applications.

PMID- 1368989
TI  - Semisynthetic fluorohydrolases prepared by chemical modification of ribonuclease.
AB  - A process for conformational modification of protein, which we have previously
      reported, was investigated as a means of generating fluorohydrolase activity in
      bovine ribonuclease (RNase). The resulting modified RNase had catalytic activity
      that depended upon the chosen modifier. Bovine pancreatic ribonuclease, modified
      by addition of hexamethylphosphoramide (HMPA) at pH 3, was derivatized with
      diimidates of chain lengths from C1 to C8. The derivative with the highest
      activity was obtained when RNase was crosslinked with dimethyl pimelimidate (C5).
      This derivative, which was active over a pH range of 6.5 to 8.0 with an optimum
      pH of 7.4, hydrolyzed phenylmethylsulfonylfluoride (PMSF) and the potent
      acetylcholinesterase inhibitor, diisopropyl phosphorofluoridate (DFP). The mean
      fluorohydrolase activity for four preparations using dimethyl pimelimidate was
      0.8 +/- 0.2 U mg-1. Gel filtration on G-75 Sephadex and SDS-polyacrylamide gel
      electrophoresis showed components having a molecular weight of 13,000 and 27,000,
      with activity restricted to the 27,000 molecular weight fraction. After gel
      filtration, the specific activity was 9.1 +/- 2.4 U mg-1, resulting in a
      molecular activity of 125 min-1. The mechanism of this unique transformation of
      RNase into a fluorohydrolase is not known, nor has the location of the active
      site been determined.

PMID- 1368990
TI  - Synthesis of esters using a nylon-immobilized lipase in batch and continuous
      reactors.
AB  - Direct esterifications using a nylon-immobilized lipase from Candida cylindracea
      were carried out in batch and continuous-flow reactors. The immobilized enzyme
      was effective in catalyzing the synthesis of ethylpropionate, isoamylpropionate,
      and isoamylbutyrate. With ethanol dissolved in hexane as a substrate, the maximum
      initial esterification rate was 0.02 mole/(h x g of immobilized protein), but the
      enzyme was stable only when the substrate concentrations were lower than 0.2 M.
      With isoamyl alcohol in hexane as a substrate, esterification rates as high as
      0.085 mole/(h x g of immobilized protein) were observed and the immobilized
      enzyme was stable over a much broader concentration range. However, in this case,
      the use of a solvent, such as hexane, was not necessary for esterification, and
      the enzyme could be employed in equimolar acid/alcohol mixtures. A packed-bed
      reactor was operated successfully for the continuous synthesis of esters. The
      reactor was stable for long periods of time, and the steady-state performance
      could be accurately predicted on the basis of batch reaction experiments.

PMID- 1368991
TI  - Resolution of 4-amino-cyclopentanecarboxylic acid methyl esters using hydrolytic
      enzymes.
AB  - A number of esterases (EC 3.1.1.1) and lipases (EC 3.1.1.3) of microbial and
      mammalian origin were screened for the ability to resolve racemic 4-amino
      cyclopentanecarboxylic acid methyl ester derivatives as potential intermediates
      in the production of carbocyclic nucleosides. Surprisingly, functionalization of
      the remote amino group had a profound effect on both the rate and
      enantioselectivity of hydrolysis of the methyl ester. 4-(Benzoylamino)-2
      cyclopentenecarboxylic acid, methyl ester (V) with pig liver esterase gave the
      highest enantioselectivity. The residual ester, which was of the correct absolute
      stereochemistry [(+) 1S, 4R] for carbocyclic nucleoside synthesis, could be
      obtained in high optical purity. Optimization of pH, solvent type, and
      concentration improved the enantioselectivity of the process by a further
      twofold.

PMID- 1368992
TI  - ELISA-based quantification of cibacron blue F3GA used as ligand in affinity
      chromatography.
AB  - The development of an enzyme-linked immunosorbent assay (ELISA) for Cibacron Blue
      F3GA is reported. It quantifies a trace amount of blue dye used as an affinity
      chromatography ligand, rendering possible the measurement of traces of leached
      dye. Polyclonal antibodies were prepared after conjugation on the dye on KLH and
      injection into rabbits. The ELISA test was based on the competitive inhibition
      between a hemoglobin-dye complex adsorbed on the wells of a titration microplate
      and a free dye. The sensitivity of the assay was about 1000 times higher than a
      classical spectrophotometric assay and was modulated by some chemical
      substituents to the dye. The described ELISA assay was also successfully applied
      to the quantification of dye traces in the presence of human albumin.

PMID- 1368993
TI  - Rapid large-scale preparation of recombinant Erwinia chrysanthemi L-asparaginase.
AB  - L-asparaginase from Erwinia provides an alternative to the enzyme from E. coli
      for the effective treatment of acute lymphoblastic leukaemia. A procedure was
      required for the large-scale partial purification of the recombinant Erwinia
      enzyme cloned and expressed in Erwinia. Enzyme was extracted from Erwinia at high
      pH and extraneous protein precipitated at low pH. S-Sepharose FF was selected as
      the medium of choice for the chromatography step since it was adequate for the
      high flow rates required (linear flow rate 315 cm h-1) and the methylsulphonate
      functional groups exploited the high pI of the enzyme by allowing binding of L
      asparaginase at pH 4.8 while most of the other proteins passed through the
      column. The useful capacity of the matrix was up to 34 mg enzyme/ml matrix at a
      linear flow rate of 95 cm h-1 and 15.4 mg enzyme/ml matrix at a linear flow rate
      of 315 cm h-1. Weakly bound protein was removed by a wash at pH 6.0. The L
      asparaginase was eluted by a wash at pH 6.8 (linear flow rate 95 cm h-1) and was
      substantially pure, only requiring polishing steps to be suitable for use as a
      parenteral agent. The purity of the protein was complemented by a 92% recovery of
      active enzyme from this cation-exchange matrix.

PMID- 1368994
TI  - Sequential membrane-based purification of proteins, applying the concept of
      multidimensional liquid chromatography (MDLC).
AB  - A purification method for formate dehydrogenase from Candida boidinii has been
      designed by using a sequence of membrane-based adsorbents. The membranes carrying
      ion-exchange and dye ligands (Sartobind) are general-purpose adsorbents for
      proteins. The membranes were used in an on/off mode. A sequence of cation
      exchange, dye-ligand and anion exchange allows to purify the enzyme as judged by
      SDS-PAGE and assay of specific activity. The sequence of ligands and the buffer
      conditions were chosen in such a way that the fraction eluted from one membrane
      could be directly loaded on the next membrane. Thereby an integrated version of
      MDLC was realized with membrane-based adsorbents. The excellent scaleability from
      micro- to laboratory scale (factor 40) indicates that the method could afford a
      general approach to develop purification trains since the micro-scale allows for
      a rapid screening of adsorbent types and sequences.

PMID- 1368995
TI  - Synthesis of dye conjugates of ethylene oxide-propylene oxide copolymers and
      application in temperature-induced phase partitioning.
AB  - Synthesis of conjugates of the ethylene oxide/propylene oxide copolymer UCON 50
      HB-5100 and the triazine dyes Cibacron Blue F3G-A and Procion Yellow HE-3G is
      described. The UCON-dye conjugate of Procion Yellow HE-3G is used as a ligand for
      affinity partitioning of glucose-6-phosphate dehydrogenase from bakers' yeast.
      The enzyme is first partitioned in a two-phase system composed of UCON, UCON
      ligand and dextran, and the two phases isolated in separate containers. A small
      amount of salt is then added to the upper phase, which contains the UCON-ligand
      enzyme complex, and the temperature increased above the cloud point of the UCON
      polymer to give a new two-phase system. The new two-phase system consists of an
      upper salt/water phase containing free enzyme and a lower UCON/water phase
      containing free UCON-ligand. Temperature-induced phase partitioning is thus seen
      to be of much assistance in dissociating enzyme-ligand complex, recovering enzyme
      and recycling UCON-ligand.

PMID- 1368996
TI  - Ultra sensitive detection of Listeria monocytogenes in milk by the polymerase
      chain reaction (PCR).
AB  - The polymerase chain reaction (PCR) has been used to detect Listeria
      monocytogenes in whole milk at a level of 0.1 cfu per 30 ml. This high degree of
      sensitivity has been achieved following enzymatic digestion, polysulphonone
      membrane filtration and amplification of a nucleotide sequence within the
      promoter region of hlyA. Key elements of the procedure are the absence of
      enrichment culture and a complete solubilization of the membrane filter, ensuring
      total nucleic acid recovery. The simplicity of the protocol coupled with high
      sample volumes and exquisite sensitivity extends the relevance of PCR within food
      and environmental microbiology.

PMID- 1368997
TI  - Genetic approaches to protein structure and function: point mutations as
      modifiers of protein function.
AB  - In this review, I summarize data in the biological literature which underscore
      the utility of a genetic approach to protein structure/function problems, with
      emphasis on binding phenomena, particularly of cytokine and growth
      factor/receptor interactions. Useful parallels or contrasts to chemical
      ligand/receptor systems and DNA binding protein interactions are examined where
      they simplify the analysis of protein ligand/receptor interactions. This approach
      was prompted by the fact that purely rational approaches, based on resolution of
      the three dimensional structure of proteins, are limited because such data is
      available for fewer than 3% of the 17,000 proteins for which the amino acid
      sequence has been deduced by molecular biology techniques.

PMID- 1368998
TI  - Polyethylene glycol enhanced protein refolding.
AB  - Previous studies on the refolding of recombinant bovine carbonic anhydrase B
      (CAB) indicated that polyethylene glycol (PEG) significantly enhanced the
      recovery of active protein by reducing aggregation. To further test the ability
      of PEG to enhance refolding, three recombinant human proteins, deoxyribonuclease
      (rhDNAse), tissue plasminogen activator (rhtPA), and interferon-gamma (rhIFN
      gamma) were refolded in the presence of PEG (3350 MW). rhDNAse produced from CHO
      cells was denatured in 7.2 M urea and refolded by rapid dilution to 4.0 M urea
      and 0.20 mg/ml protein. When a final PEG to rhDNAse molar ratio of 5 to 1 (0.1
      milligram PEG, 3350 MW) was used in the dilution buffer, refolding was improved
      by 30% to yield complete recovery of active protein. Impure E. coli derived
      inclusion body preparations of rhDNAse were solubilized in 8 M urea and refolded
      by dilution to 4 M urea and 0.10 mg/ml protein. Refolding with a dilution buffer
      which yielded a final PEG to rhDNAse molar ratio of 10 to 1 (0.1 milligram PEG,
      3350 MW) resulted in a three-fold increase in the recovery of active protein.
      When PEG was used in the dilution buffer, aggregation of rhDNAse did not occur
      during refolding in either case. rhtPA produced from CHO cells was denatured in 5
      M guanidine hydrochloride (GuHCl) and refolded by rapid dilution to 0.10 M GuHCl
      and 0.20 mg/ml protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1368999
TI  - Light-dependent, covalent immobilization of biomolecules on 'inert' surfaces.
AB  - We describe a novel, versatile procedure for the light-dependent immobilization
      of ligands to 'inert' material surfaces. Covalent immobilization of ligands
      differing in chemical nature and complexity is accomplished under mild and non
      destructive conditions. Topical interaction of ligands with organic or inorganic
      surfaces is mediated by photoactivable polymers with carbene generating
      trifluoromethyl-aryl-diazirines which serve as linker molecules. Light activation
      of aryl-diazirino functions at 350 nm yields highly reactive carbenes, and
      covalent coupling is achieved by simultaneous carbene insertion into both the
      ligand and inert surface. Thus, reactive functional groups are not required on
      either the ligand or the supporting material. These procedures are applicable
      whenever ligands, from molecules to cells--synthetically or genetically produced,
      or isolated from biological sources--need to be immobilized for improved
      performance.

PMID- 1369000
TI  - Oligonucleotide and amplification fingerprinting of wild species and cultivars of
      banana (Musa spp.).
AB  - DNA oligonucleotide and amplification fingerprinting have been successfully used
      to detect genetic polymorphisms in 15 representative species and cultivars of the
      genus Musa, comprising AA, AAA, AAAA, AAB, ABB, and BB genotypes. In-gel
      hybridization of Hinf I-digested genomic banana DNA to the 32P-labeled synthetic
      oligonucleotides (GATA)4, (GTG)5, and (CA)8 revealed considerable polymorphisms
      between Musa species and cultivars. The fingerprint patterns proved to be
      somatically stable and did not show differences between individual plants of
      'Grand Nain' (AAA genotype). Dendrograms based on oligonucleotide fingerprint
      band sharing data proved to be consistent with most of the known features of the
      history of banana and plantain cultivation and evolution, respectively. DNA
      samples from the same banana species and cultivars were also amplified by PCR
      using single or pairwise combinations of short oligonucleotide primers.
      Amplification products were separated on agarose or polyacrylamide gels and
      visualized by ethidium bromide or silver staining, respectively. Polymorphic
      patterns were obtained with some but not all primers. By using the CCCTCTGCGG
      primer in simplex and/or duplex PCR, the induced mutant 'GN60A' was clearly
      recognized from its original variety 'Grand Nain'. Both fingerprint techniques
      allowed the detection of bands characteristic for the A and B genome. This DNA
      fingerprinting technology has potential application in several areas of Musa
      improvement.

PMID- 1369001
TI  - Gene transfer to tumor-infiltrating lymphocytes and other mammalian somatic cells
      by microprojectile bombardment.
AB  - We demonstrate the application of particle delivery to the transformation of
      mammalian somatic cells. Two mouse T-lymphocyte cell lines and Chinese hamster
      ovary (CHO) cells were transformed transiently with the RSV-ADH (alcohol
      dehydrogenase) gene. Stable gene transfer was also demonstrated in CHO cells at a
      frequency of 6 x 10(-4) and in T-cells at a frequency of 1 x 10(-4), using beta
      Gal/neomycin-resistance gene constructs. The helium gas acceleration mechanism
      (PDS 1000/He) and particle delivery method allowed better velocity control and
      particle dispersion than the gunpowder driven instrument. These improvements have
      increased cell viability, transformation efficiency, and cellular targets.

PMID- 1369002
TI  - Food biotechnology: truth in advertising.

PMID- 1369003
TI  - Receptor screening and the search for new pharmaceuticals.

PMID- 1369004
TI  - Elective affinities: the art of chromatography.

PMID- 1369005
TI  - Heat transfer in bubble column and airlift bioreactors: Newtonian and non
      Newtonian fermentation broths.
AB  - A theoretical model has been developed for heat transfer in bubble column and
      airlift bioreactors, which is applicable for Newtonian and non-Newtonian
      fermentation media. The proposed model is based on a similarity between heat
      transfer in gas-sparged pneumatic reactors and turbulent natural convection. The
      applicability of the proposed model was discussed using a wide range of
      experimental data, and good agreement was obtained.

PMID- 1369006
TI  - Hydraulic characteristics of biological filters.
AB  - Relationships between the removal efficiency and the hydraulic regimes of
      trickling filters were investigated. At low flow rates, where break-up of liquid
      jets occurs and drops form, completely mixed conditions prevail. For large
      hydraulic loadings effluent concentrations were calculated by means of a
      dispersed plug flow model. The ranges of validity of these models were studied
      theoretically. The effects of drop formation and breakage of liquid jets on the
      substrate utilization are expressed in terms of hydraulic and physical properties
      of the media and liquid.

PMID- 1369007
TI  - Molecular cloning, nucleotide sequence and expression of the structural gene for
      a thermostable alkaline protease from Bacillus sp. no. AH-101.
AB  - Alkaliphilic Bacillus sp. no. AH-101 produces an extremely thermostable alkaline
      serine protease that has a high optimum pH (pH 12-13) and shows keratinolytic
      activity. The gene encoding this protease was cloned in Escherichia coli and
      expressed in B. subtilis. The cloned protease was identical to the AH-101
      protease in its optimum pH and thermostability at high alkaline pH. An open
      reading frame of 1083 bases, identified as the protease gene, was preceded by a
      putative Shine-Dalgarno sequence (AAAGGAGG) with a spacing of 11 bases. The
      deduced amino acid sequence revealed a pre-pro-peptide of 93 residues followed by
      the mature protease comprising 268 residues. AH-101 protease showed slightly
      higher homology to alkaline proteases from alkaliphilic bacilli (61.2% and 65.3%)
      than to those from neutrophilic bacilli (54.9-56.7%). Also AH-101 protease and
      other proteases from alkaliphilic bacilli shared common amino acid changes and a
      four amino acid deletion when compared to the proteases from neutrophilic
      bacilli. AH-101 protease, however, was distinct among the proteases from
      alkaliphilic bacilli in showing the lowest homology to the others.

PMID- 1369008
TI  - Identification of rate-limiting steps in cephalosporin C biosynthesis in
      Cephalosporium acremonium: a theoretical analysis.
AB  - A kinetic model describing the biosynthesis of cephalosporin C in Cephalosporium
      acremonium has been developed to identify the rate-limiting step(s). Using this
      model and in-vitro kinetic data of the biosynthetic enzymes, the production
      kinetics of cephalosporin C were examined theoretically. The predicted time
      profile of the specific production rate during batch culture is in good agreement
      with that of experimental results published previously. Sensitivity analysis
      indicates that delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) synthetase
      is the rate-limiting enzyme. Our analysis also predicts that increasing ACV
      synthetase enhances the production rate initially until expandase/hydroxylase
      becomes rate-limiting. Furthermore, increasing expandase/hydroxylase reduces the
      accumulation of penicillin N, and thus, enhances the production of cephalosporin
      C. Based on our analysis, amplifying both ACV synthetase and
      expandase/hydroxylase concurrently should enhance the production rate to a great
      extent.

PMID- 1369009
TI  - Production of alginate beads by emulsification/internal gelation. I. Methodology.
AB  - Small diameter alginate beads (microspheres) were formed via internal gelation of
      alginate solution emulsified within vegetable oil. Gelation was initiated by
      addition of an oil-soluble acid thereby reducing the pH of the alginate solution
      and releasing soluble Ca2+ from the citrate complex. Smooth, spherical, micron
      sized beads were formed. The mean diameter ranged from 200 to 1000 microns,
      controlled by the reactor impeller design and rotational speed. The technique has
      potential for large-scale and continuous applications in immobilization.

PMID- 1369010
TI  - Use of lipases in the resolution of racemic ibuprofen.
AB  - Resolution of (R,S)-ibuprofen enantiomers by esterification in different organic
      solvents was studied using Candida cylindracea lipase. This enzyme preparation
      had high enantiospecificity for S(+)-ibuprofen in the esterification reaction of
      a racemic ibuprofen with primary alcohols. The esterification yields of secondary
      alcohols were much lower than those of primary alcohols. Esterification with
      tertiary alcohols was not observed. The synthesis of esters was profoundly
      affected by the amount of water in the reaction mixture. C. cylindracea lipase
      was active only in very hydrophobic solvents. The esterification activity of the
      lipase was reduced significantly by addition of water. The R- and S-enantiomers
      of ibuprofen were determined without derivatization by HPLC using a chiral
      column.

PMID- 1369011
TI  - DNA amplification fingerprinting of bacteria.
AB  - We have amplified short arbitrary stretches of total bacterial DNA to produce
      highly characteristic and complex DNA fingerprints. This DNA amplification
      fingerprinting (DAF) strategy involves enzymatic amplification of DNA directed by
      a single arbitrary oligonucleotide primer. Amplification produces a
      characteristic spectrum of products that is adequately resolved by polyacrylamide
      gel electrophoresis and visualized by silver staining. Although DAF is simple in
      concept, we found that amplification parameters must be within an optimal range
      for reproducibility. We establish a safe window for these parameters, which
      include magnesium, primer and enzyme concentration as well as cycle number. The
      refined procedure was used to distinguish between clinical isolates of
      Streptococcus uberis, Klebsiella pneumoniae, and Escherichia coli. The use of
      template DNA concentrations higher than 1 ng.microliters-1 and high MgCl2 levels
      was especially important for reproducibility when amplifying small bacterial
      genomes. We tested a truncated Thermus aquaticus DNA polymerase, the Stoffel
      fragment, and found it more tolerant of reaction conditions, more efficient in
      the amplification of short products, and able to produce more informative
      fingerprints when compared to the normal thermostable polymerase from which it
      was derived. Because DAF produces representative fingerprints quickly and
      reliably from bacteria regardless of prior genetic or biochemical knowledge, we
      anticipate the general use of this diagnostic tool for bacterial identification
      and taxonomy.

PMID- 1369012
TI  - Gene-dose-dependent expression of soluble mammalian cytochrome b5 in Escherichia
      coli.
AB  - A synthetic structural gene encoding a mammalian cytochrome b5, carrying an
      optimised ribosomal binding sequence, was tandemly polymerised ranging from one
      (n = 1) to six (n = 6) gene copies. The gene, placed in p lambda-ncyt under the
      control of the lambda PL promoter, transcribed mono- to hexahomocistronic mRNA,
      expressing one to six copies of cytochrome b5. The expressed levels of cytochrome
      b5 in Escherichia coli p lambda-ncyt corresponded linearly with the gene dose
      when up to five copies were present; saturating build-up of the recombinant
      protein was reached at six gene copies. Cells bearing p lambda-6cyt produced 75
      micrograms cytochrome b5/ml of unit optical density at 600 nm culture,
      constituting 55% of the soluble bacterial protein. The recombinant protein
      accumulated predominantly in a haem-deficient, apoform, together with lesser
      amounts of the holocytochrome b5. Whereas the overall expressed protein (apo and
      holo forms) was gene dose dependent, there was an inverse relationship between
      holocytochrome b5 production and gene dose. Incubation of the thermally induced
      bacterial lysates with exogenous haem a converted all of the soluble
      apocytochrome b5 into holocytochrome b5 that was spectrally indistinguishable
      with its native counterpart. Culture supplementation with the likely metabolic
      precursors of haem synthesis, 5-aminolevulinic acid, glycine/succinate or
      glutamate, significantly alleviated the protoporphyrin deficiency during
      hyperproduction of cytochrome b5 in E. coli.

PMID- 1369013
TI  - Application of a statistical design to the optimization of culture medium for
      recombinant interferon-gamma production by Chinese hamster ovary cells.
AB  - The importance of serum-free medium components on the growth of Chinese hamster
      ovary (CHO) cells and production of recombinant human interferon(IFN)-gamma was
      investigated. The complexity of the medium led to the adoption of a statistical
      optimization approach based on a Plackett-Burman design. From this analysis a set
      of nutritional components was identified as important for cell growth and
      recombinant protein production. Glycine was identified as an important
      determinant of specific growth rate, whereas for cell production bovine serum
      albumin (BSA), phenylalanine and tyrosine were also identified as important. BSA,
      sodium pyruvate, glutamate, methionine, proline, histidine, hydroxyproline,
      tyrosine and phenylalanine were shown to be important for IFN-gamma production.
      Other medium components, such as insulin, arginine, aspartate and serine produced
      an inhibitory effect on both cell growth and IFN-gamma production. The effect of
      the stimulatory nutrients as a whole group was tested by increasing their
      concentration in the medium. A significant improvement in specific cell growth
      rate, cell production and IFN-gamma production (up to 45%) was achieved on both
      shake-flask and fermentor cultures. An increase in the medium concentration of
      the negative variables had only a small inhibitory effect (approximately 10%) on
      the same parameters. Analysis of the effects of the group of stimulatory amino
      acids and BSA on CHO cell growth showed that the effect of the former was
      independent of BSA.

PMID- 1369014
TI  - An expression vector system providing plasmid stability and conditional suicide
      of plasmid-containing cells.
AB  - A cloning vector system was constructed on the basis of the pBR322 derivative
      pEG1 by introducing the whole parB locus of plasmid R1 cloned behind the promoter
      of the alkaline phosphatase gene (phoA) of Escherichia coli. The parB locus in
      combination with the phoA promoter ensures both (i) plasmid stabilization due to
      the post-segregational killing of plasmid-free cells during growth and (ii)
      killing of the cells induced by the potential environmental signal phosphate
      limitation. This vector, therefore, appears to be a model system for increasing
      the stability of recombinant plasmids and for decreasing the potential risks in
      the application of recombinant bacteria in industrial fermentations.

PMID- 1369015
TI  - Isolation, structure determination and biological activity of A-16686 factors A'
      1, A' 2 and A' 3 glycolipodepsipeptide antibiotics.
AB  - When Actinoplanes strain ATCC 33076, the producer of A-16686 A1, A2 and A3
      complex, is fermented in a suitable medium three additional factors, designated
      A' 1, A' 2 and A' 3 are produced. These were isolated and characterized, and were
      shown to differ from the parent components of the original complex by lacking one
      mannose unit. Bioconversion of A factors into A' factors was achieved by
      incubation with the mycelium of Actinoplanes ATCC 33076. Factor A' 2 has better
      antibacterial activity than A2 against some bacteria.

PMID- 1369016
TI  - Improved processes for the production and isolation of dynemicin A and large
      scale fermentation in a 10,000-liter fermentor.
AB  - Supplementing the culture of Micromonospora chersina sp. nov. No. M956-1 with NaI
      (0.5 mg/l) enhanced the production of dynemicin A by 35-fold in shake flask
      culture. Homogeneous dynemicin A was obtained from the whole broth extract by
      Dicalite chromatography, Sephadex LH-20 chromatography and vacuum liquid
      chromatography. Gram quantities of dynemicin A were obtained from the
      fermentation of M. chersina sp. nov. No. M956-1 in a 10,000-liter fermentor.

PMID- 1369017
TI  - Rites of passage: moving biotech proteins through the ER.

PMID- 1369018
TI  - Europe, Maastricht, and biotechnology.

PMID- 1369019
TI  - Approaching Hungarian biotechnology.

PMID- 1369020
TI  - Protein engineers: better than nature, faster than evolution.

PMID- 1369021
TI  - Emerging strategies for enhancing crop resistance to microbial pathogens.
AB  - There are marked differences in the pattern of host gene expression in
      incompatible plant:microbial pathogen interactions compared with compatible
      interactions, associated with the elaboration of inducible defenses. Constitutive
      expression of genes encoding a chitinase or a ribosome-inactivating protein in
      transgenic plants confers partial protection against fungal attack, and a large
      repertoire of such antimicrobial genes has been identified for further
      manipulation. In addition, strategies are emerging for the manipulation of
      multigenic defenses such as lignin deposition and synthesis of phytoalexin
      antibiotics by overexpression of genes encoding rate determining steps,
      modification of transcription factors or other regulatory genes, and engineering
      production of novel phytoalexins by interspecies transfer of biosynthetic genes.
      The imminent cloning of disease resistance genes, further molecular dissection of
      stress signal perception and transduction mechanisms, and identification of genes
      that affect symptom development will provide attractive new opportunities for
      enhancing crop protection. Combinatorial integration of these novel strategies
      into ongoing breeding programs should make an important contribution to
      effective, durable field resistance.

PMID- 1369022
TI  - Controlled antibody delivery systems.
AB  - We have developed methods for controlling the release of antibodies (Ab) from
      biocompatible polymers. Human Ab, human Ab fragments, and mouse monoclonal
      antibody (mAb) directed against human chorionic gonadotropin (anti-hCG) were
      incorporated into matrices of poly(ethylene-co-vinyl acetate), which is stable in
      biological environments. Human Ab and bovine gamma-globulin were also
      incorporated in biodegradable matrices of a poly-anhydride copolymer composed of
      a stearic acid dimer and sebacic acid. Abs were slowly released from all the
      polymeric carriers during 30 days of continuous immersion in buffered saline. The
      ability of anti-hCG to bind antigen was retained following release from EVAc
      matrices. Only minor Ab aggregation was observed following release from either
      polymer. Polymeric delivery systems, similar to those described here, may become
      an important element in the delivery of mAbs to humans for immunoprotection
      against infectious diseases or the delivery of mAb-conjugates for immunotherapy
      against cancer.

PMID- 1369023
TI  - "Primatization" of recombinant antibodies for immunotherapy of human diseases: a
      macaque/human chimeric antibody against human CD4.
AB  - Immunoglobulin variable region genes from non-human primates, cynomolgus
      macaques, were shown to have 85%-98% homology with human immunoglobulin sequences
      and yet macaques are phylogenetically distant enough to respond against conserved
      human antigens. Immunoglobulin genes were isolated from monkeys immunized with
      human CD4 antigen and a human/monkey chimeric anti-CD4 antibody with 91-92%
      homology to human immunoglobulin framework regions was cloned and expressed. The
      antibody has an apparent affinity of 3.2 x 10(-11) M and exhibits potent
      immunosuppressive properties in vitro.

PMID- 1369025
TI  - Trypanosoma cruzi flagellar repetitive antigen expression by recombinant
      baculovirus: towards an improved diagnostic reagent for Chagas' disease.
AB  - We constructed a recombinant baculovirus that expressed part of a Trypanosoma
      cruzi flagellar repetitive antigen (FRA). Both cell- associated and secreted
      forms of recombinant FRA were detected in cultures of virus-infected Spodoptera
      frugiperda (Sf9) cells. These forms show a complex pattern after polyacrylamide
      gel electrophoresis and Western blot analysis using either an anti-FRA rabbit
      serum or human Chagasic sera. Competitive Western-blot experiments revealed that
      all bands react with the same antibodies as a bacterially-derived FRA. Polymerase
      chain reaction and Southern blots of the recombinant viral DNA also showed a
      complex pattern, suggesting the presence of more than one repeat unit in the
      viral genome. When tested against a panel of human sera from an endemic area for
      Chagas' disease, FRA recombinant-Sf9 culture supernatant showed the same
      reactivity as purified FRA produced in bacteria.

PMID- 1369024
TI  - The two major xylanases from Trichoderma reesei: characterization of both enzymes
      and genes.
AB  - As a first step to exploit the potential of Trichoderma reesei to produce
      hemicellulases, we have purified two endo-beta-1,4-xylanases (1,4-beta-D-xylan
      xylanohydrolase, EC 3.2.1.8) and cloned their genes. The enzymes were isolated
      from culture filtrates of T. reesei C30 grown on xylan as a carbon source, using
      two steps of cation exchange chromatography. They exhibited molecular weights of
      19 (XYN I) and 21 (XYN II) kD, and isoelectric points of 5.2 and 9.0,
      respectively. These enzymes differed in their pH optimum for activity and
      affinity for xylan, and accounted for more than 90% of the total xylanolytic
      activity of the fungus. The purified enzymes were subjected to N-terminal
      sequence analysis, and after cleavage with trypsin and endoproteinase Glu-C the
      resulting peptides were sequenced. Oligonucleotides based on these sequences were
      used to clone gene fragments via PCR, and these were used as probes to isolate
      full-length copies of xyn1 and xyn2 from a lambda gene bank of T. reesei. The
      products of xyn1 and xyn2 share considerable homology, but the enzyme encoded by
      xyn2 appears to more closely resemble several other bacterial and fungal
      xylanases than does that of xyn1.

PMID- 1369027
TI  - A plate liquid scintillation counter that permits more tests and smaller sample
      volumes.

PMID- 1369026
TI  - A single-step method for the preparation of liquid cell culture media from
      powder.

PMID- 1369028
TI  - Optimization of enzymatic digest conditions using a laser desorption mass
      analyzer.

PMID- 1369029
TI  - Radiation safety in the laboratory.

PMID- 1369030
TI  - Standard protein mixture for assessing anion exchange column performance.

PMID- 1369031
TI  - Testing polystyrene microplates for coating uniformity.

PMID- 1369032
TI  - A compact system for the rapid molecular weight measurement of peptides and
      proteins.

PMID- 1369033
TI  - Recombinant human insulin.
AB  - Insulin is a well-characterized peptide that can be produced by recombinant DNA
      technology for human therapeutic use. A brief overview of insulin production from
      both traditional mammalian pancreatic extraction and recombinant bacterial and
      yeast systems is presented, and detection techniques, including electrophoresis,
      are reviewed. Analytical systems for insulin separation are principally based on
      reversed-phase chromatography, which resolves the deamidation product(s)
      (desamido insulin) of insulin, proinsulin, and insulin. Process-scale separation
      is a multistep process and includes ion exchange, reversed-phase, and size
      exclusion chromatography. Advantages and/or disadvantages of various separation
      approaches, as described by the numerous literature references on insulin
      purification, are presented.

PMID- 1369034
TI  - Spatial distribution of mammalian cells grown on macroporous microcarriers with
      improved attachment kinetics.
AB  - Vero and HepG2 cells were cultivated on macroporous gelatin microcarriers
      prepared by the calcium carbonate inclusion method. Cell attachment to these
      microcarriers was slow. For HepG2 cells the subsequent growth was poor.
      Modification of the microcarriers by incorporation of (diethylamino)ethyl-HCl
      improved HepG2 attachment and subsequent growth. Optical sectioning with confocal
      microscopy allowed visualization of the distribution of cells within
      microcarriers. In most microcarriers, cells were found to preferentially populate
      regions close to the external surface and some cavities in the interior. Despite
      the incomplete occupancy of the interior of the microcarriers, high cell
      concentrations were achieved.

PMID- 1369035
TI  - The use of pressure to modify enzyme activity in reversed micelles.
AB  - Pressurization of enzyme-containing AOT-water-isooctane reversed micelles with
      low molecular weight gases leads to markedly different responses in activity
      characteristics. Microbial lipases exhibit a total cutoff in activity with as low
      a pressure as 2 MPa and a remarkable activity regain with depressurization. The
      observation also holds for reaction in monophasic organic solvents. The protease,
      alpha-chymotrypsin, is unaffected by pressurization until a critical pressure
      wherein micellar instability occurs. The use of pressure as a switch for lipase
      reaction in nonaqueous media is discussed.

PMID- 1369036
TI  - Cation-exchange displacement chromatography of proteins with protamine
      displacers: effect of induced salt gradients.
AB  - Protamine was investigated for its utility as a protein displacer in cation
      exchange systems. Although the protamine solution contained several variants of
      the molecule, the high affinity of all of the components in this heterogeneous
      biopolymer enabled it to act as an efficient protein displacer. To facilitate
      parameter estimation of the protamine, a preliminary purification was carried out
      by preparative elution chromatography. Chromatographic parameters of both the
      feed proteins and protamine displacer were obtained for use in a multicomponent
      steric mass action ion-exchange displacement model. Model simulations were
      compared to displacement results under both moderate and intense induced salt
      gradient conditions. In both cases, excellent agreement was obtained between the
      displacement experiments and theoretical predictions. In addition, these studies
      serve to dramatize the importance of induced salt gradients in ion-exchange
      displacement systems.

PMID- 1369037
TI  - Biomimetic metal-sorbing vesicles: Cd2+ uptake by phosphatidylcholine vesicles
      doped with ionophore A23187.
AB  - Unilamellar phosphatidylcholine vesicles, harboring the ionophore, A23187, in the
      bilayer and the water-soluble chelating agent, nitrilotriacetate, in the vesicle
      interior, rapidly sequester and concentrate Cd2+ from dilute aqueous solution.
      Metal-sorbing vesicle permeabilities for cadmium ion at 5 ppm (42.8 microM)
      ranged from 8.09 x 10(-7) to 1.27 x 10(-4) cm/s for surface A23187 concentrations
      of 0.22-2.27 pmol/cm2 (which correspond to lipid:carrier molar ratios of 2000:1
      to 200:1) and pH's from 5.5 to 8.5. The Cd2+ permeability shows linear variation
      with carrier concentration under the conditions studied. As pH is decreased, an
      increasing fraction of the A23187 becomes protonated, and the permeability
      exhibits a positive linear relationship with a function related to that for the
      fraction of unprotonated carrier. These noncovalently assembled, metal-sorbing
      vesicles exhibit shelf lives of several months and remain stable throughout
      typical metal sorption studies.

PMID- 1369038
TI  - Effect of protein adsorption on the transport characteristics of asymmetric
      ultrafiltration membranes.
AB  - The effects of bovine serum albumin adsorption on the transport characteristics
      of asymmetric poly(ether sulfone) ultrafiltration membranes were determined using
      polydisperse dextrans with gel permeation chromatography. Actual dextran sieving
      coefficients were evaluated from observed sieving data for both the clean and
      preadsorbed membranes using a stagnant film model. The flux dependence of the
      actual dextran sieving coefficients was used to evaluate the intrinsic membrane
      hindrance factors for convective (i.e., sieving) and diffusive transport for the
      different molecular weight dextrans using classical membrane transport theory.
      Protein adsorption caused a reduction in both dextran sieving and diffusion, with
      the magnitude of the reduction a function of the dextran molecular weight and
      pore size. The effects of adsorption on the specific pore area and the membrane
      porosity were then determined using a recent model for solute transport through
      asymmetric ultrafiltration membranes. The data indicate that protein adsorption
      occurs preferentially in the larger membrane pores, causing a greater reduction
      in solute sieving compared to the membrane hydraulic permeability and porosity
      than would be predicted on the basis of either a simple pore blockage or pore
      constriction model.

PMID- 1369039
TI  - Applications of ultrafast HPLC to process development of recombinant DNA-derived
      proteins.
AB  - The application of ultrafast HPLC to the development of recovery processes for
      proteins produced by recombinant DNA technology has been explored using wide-pore
      HPLC resins and instrumentation designed for rapid analysis. High-resolution
      analysis of complex samples was achieved with a total analysis time of less than
      5 min from injection to injection. Fractions collected during preparative
      chromatography were analyzed by SDS gel electrophoresis and fast HPLC. Specific
      proteins in the fractions were detected and quantitated by fast HPLC providing
      real-time analysis for pooling. The technique was also applied to the formidable
      task of detecting and quantitating protein variants during the development of
      recovery processes. Several examples of post-translational variant detection are
      shown. Ultrafast HPLC is a new analytical tool that can be applied to the
      development of robust manufacturing processes producing therapeutic proteins
      essentially free of known impurities and variants.

PMID- 1369040
TI  - Recombinant beta-galactosidase production in serum-free medium by insect cells in
      a 14-L airlift bioreactor.
AB  - Spodoptera frugiperda (Sf9) insect cells were successfully cultured in serum-free
      medium in a 14-L airlift bioreactor. Cell densities as high as 1 x 10(7) cells/mL
      were achieved with specific growth rates of approximately 0.0286 h-1 (doubling
      time of 24 h). This system was also used to demonstrate the expression of a
      reported gene, beta-galactosidase (beta-gal), when cells were infected with a
      recombinant baculovirus. Approximately 0.33 mg of beta-gal/mL (i.e., 104,000
      units/mL) of medium were obtained at the 14-L scale, while about 0.95 mg of beta
      gal/mL (i.e., 285,000 units/mL) of medium were obtained in small-scale shaker
      flasks. The difference was attributed to a suboptimal infection in the large
      scale. Specific oxygen consumption rates decreased from 5.58 x 10(-17) mol
      O2/cell.s in early exponential growth to 3.13 x 10(-17) mol O2/cell.s at 3 days
      post-infection.

PMID- 1369041
TI  - On-line assessment of metabolic activities based on culture redox potential and
      dissolved oxygen profiles during aerobic fermentation.
AB  - We report here on the utility of on-line culture redox potential and dissolved
      oxygen measurements to identify metabolic changes in fermentation by
      Corynebacterium glutamicum under aerobic conditions. Metabolic changes were
      identified by observing discrepancies in the profile of culture redox potential
      and dissolved oxygen. On the basis of these measurements, we can identify the end
      of the lag phase, threonine exhaustion, and glucose exhaustion during
      fermentation.

PMID- 1369042
TI  - Isolation of vindoline from Catharanthus roseus by supercritical fluid
      extraction.
AB  - Vindoline was extracted from the leaves of Catharanthus roseus over the ranges of
      35-70 degrees C and 100-300 bar using supercritical carbon dioxide with and
      without the addition of 3 wt % ethanol as a cosolvent. The vindoline contents in
      the extracts were determined by HPLC and identified by LC/MS. The remarkable
      highest vindoline concentration, 58 wt %, was obtained at the lowest temperature,
      35 degrees C, and the highest pressure, 300 bar, of this study. The use of a
      cosolvent only slightly improved the extraction yields or selectivities at some
      experimental conditions.

PMID- 1369043
TI  - Synthesis of some new 3-(2'-heterocyclicethyl)-2-methyl-3,4- dihydroquinazolin-4
      one derivatives as antimicrobial agents.
AB  - 3-(2'-Chloroethyl)-2-methyl-3,4-dihydroquinazolin-4-one was reacted with
      acetylacetone, ethyl acetoacetate and diethylmalonate in the presence of sodium
      ethoxide to afford the alkylation products IV, V and VI. Compounds IV, V and VI
      were reacted with hydrazine hydrate, phenylhydrazine, hydroxylamine
      hydrochloride, urea and thiourea to yield 3-(2'-heterocyclicethyl)-2-methyl-3,4
      dihydroquinazolin-4-on e derivatives VII-XV. The structures of the synthesized
      compounds were elucidated by elemental analyses and spectroscopic (IR and 1H-NMR)
      analyses. The prepared compounds were tested for their antimicrobial activities
      in comparison with tetracycline as a reference compound.

PMID- 1369044
TI  - Spiroheterocyclic system. Part IV: Novel azo dye sulpha drugs of
      spiroheterocyclic naphthenes.
AB  - Novel azo-dyes have been synthesized by diazotization of 4-amino benzene-4'
      (substituted heterocyclo) sulphonamide derivatives and coupling with 1-oxa-4-thia
      spiro[4,4]nonan-2-one (I) and/or with 1-oxa-4-thia- spiro[4,5]decan-2-one (I') in
      acid medium to give the corresponding 3-azo-(4'-substituted benzenesulphonamido)
      1-oxa-4-thia-spiro[4,4]nonan-2-one (II-IX) and/or 1-oxa-4-thia-spiro[4,5]decan-2
      one (II'-IX'] as spiro-ligands. Treatment of these ligands with metal salts of
      iron (Fe3+), copper (Cu2+) and mercury (Hg2+) as chlorides in ethanolic solution
      furnished the corresponding metal chelates (IIa-c-IXa-c) and/or (II'a-c-IX'a-c).
      The compounds were tested in vitro for antimicrobial activity to study the
      structure-activity relationship.

PMID- 1369045
TI  - Oxygen utilisation by isopenicillin N synthase from Penicillium chrysogenum.
AB  - The enzyme isopenicillin N synthase (IPNS) converts delta-(L-alpha- aminoadipyl)
      L-cysteinyl-D-valine (ACV) to isopenicillin N; an equimolar amount of oxygen is
      used in this oxidative ring closure reaction. Oxygen uptake rates of the reaction
      catalysed by partially purified IPNS from Penicillium chrysogenum SC 6140 and P2
      were measured using an oxygen electrode. In contrast to published properties of
      Cephalosporium acremonium IPNS, the enzyme from P. chrysogenum was not stimulated
      by the addition of glutathione and showed reduced stimulation by Fe2+. The
      analysis of oxygen uptake rates showed the reaction to be first order with
      respect to oxygen concentration and the Km for ACV to be 0.4 mmol dm-3. The
      implications of these results for cell-free reactions using this enzyme and
      penicillin fermentations are discussed.

PMID- 1369047
TI  - Extended summaries. SCI Solvent Extraction and Ion Exchange Group. Silver Jubilee
      celebration meeting.

PMID- 1369046
TI  - Extraction of penicillin G from simulated media by an emulsion liquid membrane
      process.
AB  - The extraction of penicillin G from simulated media was performed by
      water/oil/water (w/o/w) emulsion liquid membranes (ELMs) and studied under
      various operational conditions in a batch system. The degree of extraction
      achieved was between 80% and 95% under specific conditions. A concentration of
      greater than nine times the initial concentration of penicillin G in the external
      phase was obtained in the internal phase. The pH of the internal aqueous
      solution, containing a basic salt, was theoretically calculated on the basis of
      the amount of penicillin G transported into the internal phase. The calculated
      results agreed with the experimental data well and were used to select a suitable
      type and concentration of a basic salt in the internal phase to give a pH within
      the range 5 to 8 where penicillin G was stable after the termination of
      extraction. The extraction of penicillin G was successfully performed by the ELM
      process with sodium carbonate in the internal phase.

PMID- 1369048
TI  - Ultrafiltration membranes for the separation of catalyst and products in
      homogeneous catalysis systems.
AB  - Results of preliminary studies on concentration by ultrafiltration and reuse of a
      Ru(III)EDTA complex in homogeneous catalysis are reported. A method of
      preparation and selection of conditions of making cellulose acetate membranes for
      concentrating Ru(III)EDTA is described. At an operating pressure of 75 psig (517
      kPa), the above catalyst can be concentrated to seven to eight times its initial
      concentration. The membrane used exhibits a separation of about 97.5% for the
      complex with a permeate flow rate of about 3-6 gallons per sq. ft per day. The
      catalyst activities were determined for two reactions, viz. hydroformylation of 1
      hexene and carbonylation of ammonia for five cycles of concentration followed by
      reuse. The experimental data indicated that the catalyst concentration by
      ultrafiltration for subsequent reuse is simple and attractive and can provide
      potentially energy saving alternative to the cumbersome conventional separation
      processes associated with the recovery of catalysts in homogeneous catalysis.

PMID- 1369049
TI  - A comparative study of the performance of solid supported and soluble urease for
      the enzymatic hydrolysis of urea.
AB  - The performance of both free and solid supported urease for the enzymatic
      hydrolysis of urea was studied. Kinetic analysis of reaction rate data shows that
      the kinetic data were consistent with the proposed model. Statistical tests
      validated the model. Despite the deactivation of ureases, the immobilized enzyme
      could be the choice for a technological process aiming at the detoxification of
      blood in haemoperfusion columns.

PMID- 1369050
TI  - Nitriles in heterocyclic synthesis. Part III: New sulpha drugs related to
      cyanopyridine derivatives.
AB  - 4-Hydroxyacetophenone (1) was reacted with cinnamonitrile derivatives (2-6) to
      give 3-cyano-4-(substituted phenyl)-6-(p-hydroxyphenyl)-pyridines (7-11).
      Interaction of compounds 7-9 with 4'-substituted heterocyclo-benzenesulphonyl
      diazonium chloride gave the corresponding 3-cyano-4-(substituted phenyl)-6-(3'
      azobenzene sulphonamido-4'-hydroxyphenyl) pyridines (12-29). The corresponding
      iron (III) copper (II) and mercury (II) chelates were also prepared in a 1:2
      metal-to-ligand ratio. All the synthesized compounds were characterized on the
      basis of microanalysis, IR and 1H-NMR spectrometry.

PMID- 1369051
TI  - s-triazole systems. Part IV: Novel substituted thio-s-triazole derivatives.
AB  - Interaction of (3-aryloxymethyl-4-phenyl-s-triazol-5-yl)thioacethydrazid e (1a-c)
      with phenyl isocyanate and/or with methyl/phenyl isothiocyanate gave
      semicarbazides (2a-c) and thiosemicarbazides (3a-f) respectively. Cyclization of
      (3a-f) yielded s-triazoles (4a-f). Compounds 4b,d,f were easily alkylated giving
      S-substituted thio-s-triazoles (5a-e). Furthermore, compounds 4b,d,f underwent a
      Mannich reaction to give the expected Mannich bases (6a-f). All compounds were
      fully confirmed by elemental and spectral analyses and have been screened in
      vitro for antimicrobial activity.

PMID- 1369052
TI  - An Avicel-affinity site in an Avicel-digesting exocellulase from a Trichoderma
      viride mutant.
AB  - A single form of exo-type cellulase (Exo I; MW, 65,000), purified from a
      Trichoderma viride protease-depressed mutant, HK-75, digested Avicel to
      cellobiose exowise, and hydrolyzed cellotriose, cellotetraose, and cellopentaose
      in the strict manner of splitting off by cellobiose units. Exo I, however,
      hydrolyzed cellohexaose by both cellobiose and cellotriose units. Exo I was
      proteolyzed by papain into two fragments; GPExo (MW, 9,000) and Exo I' (MW,
      56,000). The GPExo intensively adsorbed onto Avicel but did not hydrolyze it. Exo
      I' had nearly identical activity to that of intact Exo I toward
      cellooligosaccharides but was almost inert to Avicel in digestion and adsorption.
      Sequence analysis of N-terminal and C-terminal amino acids showed that GPExo was
      between Gly435 and Leu496 and Exo I' between Glu1 and Gly434 in Exo I. Exo I
      therefore consists of two domains, one for adsorption to Avicel, as demonstrated
      by the Avicel-affinity site, GPExo and the other for the cleavage of glycosidic
      linkages as demonstrated in Exo I'.

PMID- 1369053
TI  - Isolation, purification, and characterization of a new enzyme from Pseudomonas
      sp. M-27, carboxypeptidase G3.
AB  - A new type of carboxypeptidase was found in a strain of Pseudomonas sp. M-27
      isolated from soil. The cell-free extract, solubilized by colistin sulfate, was
      purified to homogeneity. This enzyme had a single peak with a molecular weight of
      60,000 on a calibrated Superdex column and consisted of four subunits of
      identical molecular weights (M(r): 15,000). The enzyme hydrolyzed predominantly
      acidic peptides and N-acyl amino acids with Glu or Asp in the C-termini. This
      enzyme was not strongly affected by thiol enzyme inhibitors (PCMB, iodoacetic
      acid) or serine protease inhibitors (DFP, PMSF), but was inhibited by metal
      chelators. The enzyme resembles carboxypeptidase G1 or G2 in its glutamate
      releasing activity. However, it acts not only on the L-form but also on the D
      form of acidic amino acids and shows affinity for the long-chain fatty acyl group
      but not the benzoyl group. Thus, as this enzyme differs from carboxypeptidase G1
      or G2, it was named carboxypeptidase G3.

PMID- 1369054
TI  - Peptide inhibitors for angiotensin I-converting enzyme from thermolysin digest of
      dried bonito.
AB  - Dried bonito (Katsuobusi), a Japanese traditional seasoning made of bonito muscle
      was hydrolyzed by various proteases and the inhibitory activity of the
      hydrolyzates for angiotensin I-converting enzyme (ACE) [EC 3.4.15.1] was
      measured. Among the digests, thermolysin digest showed the most potent inhibitory
      activity. Eight inhibitory peptides were isolated from the digest using HPLC. The
      amino acid sequences of inhibitory peptides were Ile-Lys-Pro-Leu-Asn-Tyr, Ile-Val
      Gly-Arg-Pro-Arg-His-Gln-Gly, Ile-Trp-His-His-Thr, Ala-Leu-Pro-His-Ala, Phe-Gln
      Pro, Leu-Lys-Pro-Asn-Met, Ile-Tyr, and Asp-Tyr-Gly-Leu-Tyr-Pro. By searching for
      the sequence homology in many proteins, four of them were found in the primary
      structure of actin. Asp-Met-Ile-Pro-Ala-Gln-Lys was obtained from the boiling
      water extract of dried bonito and this peptide was found in the primary structure
      of creatine kinase. Fragments of these peptides were prepared by further
      enzymatic digestion or chemical synthesis and their ACE-inhibitory activities
      were measured. Among them, Ile-Lys-Pro, Ile-Trp, Leu-Lys-Pro, and Leu-Tyr-Pro had
      higher inhibitory activity than their parental peptides. Ile-Lys-Pro suppressed
      the hypertensive activity of angiotensin I.

PMID- 1369055
TI  - Continuous chitosan hydrolyzate production by immobilized chitosanolytic enzyme
      from Enterobacter sp. G-1.
AB  - Chitosanolytic enzymes from Enterobacter sp. G-1 were immobilized on various
      carriers to continuously hydrolyze chitosan. Four different carriers were tested:
      FE-3901 (strong basic anion exchange resin, ionic binding), glutaraldehyde
      treated FE-4612 (weak basic anion exchange resin, cross-linking), Chitopearl
      (chitosan beads), and alginate calcium. Glutaraldehyde-treated FE-4612 and
      Chitopearl immobilized more protein than the others. The enzyme immobilized on FE
      3901 had the greatest activity. The activity of enzyme immobilized on FE-3901
      decreased rapidly when exposed to a continuous flow of 1% chitosan. The enzyme
      immobilized with Chitopearl retained more than 50% of its original activity after
      17 days, and the activity was fully restored by re-immobilization.

PMID- 1369056
TI  - Enzymatic synthesis of 2-chloro-4-nitrophenyl 4,6-O-3-ketobutylidene beta
      maltopentaoside, a substrate for alpha-amylase.
AB  - A transglycosylation reaction with 2-chloro-4-nitrophenyl beta-maltoside as an
      acceptor was done with 4,6-O-3-ketobutylidene maltopentaose and Bacillus macerans
      cyclodextrin glucanotransferase in an aqueous solution containing 50% n-propanol,
      and there were two main transglycosylation products. They were identified as 2
      chloro-4-nitrophenyl 4,6-O-3-ketobutylidene beta-maltopentaoside and 2-chloro-4
      nitrophenyl 4,6-O-3-ketobutylidene beta-maltohexaoside, and their yields were 30%
      and 21% respectively on the basis of the decrease of 4,6-O-3-ketobutylidene
      maltopentaose. For the production of 2-chloro-4-nitrophenyl 4,6-O-3
      ketobutylidene beta-maltopentaoside at high substrates concentrations, the
      addition of n-propanol in this reaction not only increased the solubility of 2
      chloro-4-nitrophenyl beta-maltoside sufficiently but also suppressed side
      reactions.

PMID- 1369057
TI  - Isolation and characterization of macrocarpals B--G antibacterial compounds from
      Eucalyptus macrocarpa.
AB  - Six novel phloroglucinol dialdehyde diterpene derivatives (macrocarpals B--G),
      which have antibacterial activity, were isolated from leaves of Eucalyptus
      macrocarpa. These compounds have closely related structures, the molecular
      formula for B--F being C28H40O6, and that of G being C28H38O5. The structures of
      macrocarpals B, D, and G were analyzed by means of NMR analyses.

PMID- 1369058
TI  - A novel sulfatase from Pseudomonas testosteroni hydrolyzing lithocholic acid
      sulfate.
AB  - Pseudomonas testosteroni ATCC 11996 was found to produce a novel bile acid
      sulfate sulfatase that hydrolyzes the sulfate ester bond in lithocholic acid
      sulfate (LCA-S). The enzyme synthesis was induced by several kinds of bile acids
      including LCA-S. Mn2+ functioned as an essential component for the enzyme
      synthesis and SO4(2-) suppressed it. This sulfatase hydrolyzes LCA-S to
      isolithocholic acid and sulfuric acid with inversion of alpha- to beta
      configuration of the hydroxyl group at the third position of lithocholic acid.

PMID- 1369059
TI  - Cloning and nucleotide sequencing of the antitumor antibiotic C-1027 apoprotein
      gene.
AB  - The apoprotein gene for a chromoprotein antitumor antibiotic, C-1027, was cloned
      from the producer strain, Streptomyces globisporus C-1027, and sequenced. The
      process verified that; (1) the sequence included the entire structural gene
      directing a precursor of the apoprotein (pre-apoprotein having Met1---Ala33
      leader peptide ahead of the apoprotein) and flanking regions, (2) the amino acid
      sequence of the apoprotein deduced from the base sequence perfectly matched the
      one based on protein analysis, (3) 3rd letters of the codons were 88% G or C,
      while the 1st plus the 2nd letters were 63% G or C, (4) the structural gene had
      57% homology with that of macromomycin apoprotein (mcmA) while the flanking
      regions had little homology with the corresponding ones of mcmA, except some
      homology at the -10th and -35th promoter regions, and (5) the gene was
      transcribed as a monocistronic mRNA in an early growth phase, independent of
      chromophore production.

PMID- 1369060
TI  - Molecular cloning and sequencing of the extracellular pectate lyase II gene from
      Erwinia carotovora Er.
AB  - Erwinia carotovora Er produces three extra-cellular pectate lyases (PL I, II, and
      III). The gene for pectate lyase II (pelII) of E. carotovora Er was cloned and
      expressed both in Escherichia coli and E. carotovora Er. Localization experiments
      in E. coli showed that PL II was exclusively in the cytoplasmic space, while PL
      II was excreted into the culture medium. The complete nucleotides of the pelII
      gene were sequenced and found to include one open reading frame of 1122 bp coding
      for a protein of 374 amino acid residues. From comparison of the N-terminal amino
      acid sequence between the purified PL II and the deduced protein from the
      nucleotide sequence we reached the conclusion that the mature protein is composed
      of 352 amino acids with a calculated molecular weight of 38,169 and is preceded
      by a typical signal sequence of 22 amino acid residues. PL II had 90.1% and 82.9%
      homologies with PL I and PL III in amino acid sequence, respectively.

PMID- 1369061
TI  - Inhibition of Achromobacter protease I by lysinal derivatives.
AB  - Z-Val-, Z-Pro-, Z-Leu-Leu-, and Z-Leu-Pro-lysinals and BZ-DL-lysinal were
      chemically synthesized and tested as novel inhibitors for Achromobacter protease
      I (API), a lysine-specific serine protease. Among the lysinal derivatives tested,
      Z-Val-lysinal was the most potent competitive inhibitor, its Ki being estimated
      as 6.5 nM in an esterolytic assay with Tos-Lys-OMe. In an amidolytic assay, Z-Leu
      Leu-lysinal was the most potent inhibitor and the apparent mode of inhibition was
      non-competitive. The Kis of the other lysinal derivatives in both esterolytic and
      amidolytic assays were more than 10(3) times lower than that of leupeptin. Z-Val
      lysinol, lacking the aldehyde group, was a poor competitive inhibitor. These
      results suggest that acyl-, acylaminoacyl-, and acylpeptidyllysinals function as
      a transition-state inhibitor for Achromobacter protease I.

PMID- 1369062
TI  - Effect of exercise on tissue protein synthesis in rats.
AB  - The effect of exercise on the protein metabolism in skeletal muscles
      (gastrocnemius and soleus), liver and small intestine was investigated in rats.
      Treadmill treatment for 7 d resulted in atrophy of the liver and small intestine,
      which was associated with a reduction in protein content. The rates of protein
      synthesis in the liver and small intestine were significantly suppressed in rats
      subjected to exercise. The change in protein synthesis in the visceral organs was
      mediated by the change in RNA activity (protein synthesis per unit RNA) but not
      by the change in RNA concentration. The tissue weight and the rate of protein
      synthesis in the gastrocnemius and soleus muscles were not affected by exercise.
      The results suggest that these changes in protein synthesis in the liver and
      small intestine may explain, at least partly, the atrophy of these organs which
      was observed after 7 d of exercise.

PMID- 1369064
TI  - Inhibition of protein translocation in permeabilized cells of Schizosaccharomyces
      pombe by puromycin.
AB  - To investigate protein translocation in eukaryotes, we reconstituted a protein
      translocation system using the permeabilized spheroplasts (P-cells) of the
      fission yeast Schizosaccharomyces pombe. The precursor of a sex pheromone of
      Saccharomyces cerevisiae, prepro-alpha-factor, was translocated across the
      endoplasmic reticulum (ER) of S. pombe posttranslationally, and glycosylated to
      the same extent as in the ER of S. cerevisiae. This suggested that the size of N
      linked core-oligosaccharide in the ER of S. pombe is similar to that in S.
      cerevisiae. This translocation into the ER of S. pombe was inhibited by
      puromycin, but the translocation in the P-cells of S. cerevisiae was not
      inhibited. This difference in sensitivity to puromycin was due to the membrane
      but not the cytosolic fraction. Our results suggested that the translocation
      machinery of S. pombe was sensitive to puromycin and different from that of S.
      cerevisiae.

PMID- 1369063
TI  - Metabolism of L-amino acids in a marine bacterium isolated from mackerel
      intestines in relation to eicosapentaenoic acid biosynthesis.
AB  - Metabolism of glucose and L-amino acids in an obligately aerobic marine bacterium
      isolated from Pacific mackerel intestines was investigated for the mechanism and
      pathway of eicosapentaenoic acid (EPA) biosynthesis. This bacterium could not
      uptake glucose but the cell-free extract of this bacterium had the enzymatic
      activities of L-alanine oxidase (EC 1.4.3.2), L-alanine dehydrogenase (EC
      1.4.1.1). L-serine dehydratase (EC 4.2.1.13), and malate dehydrogenase (EC
      1.1.1.40), and of seven enzymes involved in the TCA cycle of the usual aerobes.
      On the other hand, the carbon-13 concentration in cellular fatty acids of the
      bacterium, especially that in their methyl carbon atoms in contrast to their
      carbonyl carbons, increased drastically when the bacterium was grown in the
      presence of 13CH3COONa. These results indicate that: (i) the TCA cycle works in
      this bacterium, (ii) glucose is not utilized and pyruvic acid is in vivo
      synthesized from L-alanine, L-serine, and malic acid, and (iii) EPA and other
      cellular fatty acids are in vivo synthesized from acetyl coenzyme A by the usual
      de novo synthesis route.

PMID- 1369066
TI  - Overproduction of an alpha-amylase/glucoamylase fusion protein in Aspergillus
      oryzae using a high expression vector.

PMID- 1369065
TI  - Interaction of starfish embryonic cells with the complex of okadaic acid and
      monoclonal antibody specific to okadaic acid.

PMID- 1369067
TI  - Preferential suppression of delayed-type hypersensitivity by L-156,602, a C5a
      receptor antagonist.
AB  - In the course of our screening for in vivo immunomodulating substances in which
      sheep red blood cells (SRBC) and heat-killed Brucella abortus cells (thymus
      dependent and independent antigens, respectively) for antibody production assays,
      and trinitrobenzene sulfonic acid (TNBS) for delayed-type hypersensitivity (DTH)
      assay were adopted as antigens, we detected a DTH-specific suppressive activity.
      The producing organism was isolated from a soil sample collected in Ushiku City,
      Ibaraki, Japan and identified with Streptomyces sp. A1502 (FERM P-12448). The
      active component was identified with L-156,602, a C5a receptor antagonist. L
      156,602 suppressed both TNBS-induced and TNP-SRBC-induced DTH while it enhanced
      antibody production against SRBC, Brucella abortus, and TNP-SRBC. L-156,602
      significantly suppressed DTH induced by direct injection of type 1 helper T cells
      and its relevant antigen into hind-footpads, indicating that the efferent phase
      of DTH was affected by L-156,602. The results demonstrated that L-156,602
      preferentially suppressed the DTH response.

PMID- 1369069
TI  - Purification and some properties of chlorogenic acid oxidase from apple (Malus
      pumila).
AB  - Chlorogenic acid oxidase was extensively purified to homogeneity from apple flesh
      (Malus pumila cv. Fuji). The enzyme was purified 470-fold, with a total yield
      close to 70% from the plastid fraction by ammonium sulfate precipitation, gel
      filtration and ion-exchange chromatography. The molecular weight was determined
      to be 65,000 by both SDS-PAGE and gel filtration chromatography. The optimum pH
      for the enzyme activity was around 4.0, and the enzyme was stable in the range of
      pH 6-8. The pI obtained by isoelectrofocusing was 5.4, and the N-terminal amino
      acid sequence was N-Asp-Pro-Leu-Ala-Pro-Pro-. The reaction rate of the purified
      enzyme was much larger for chlorogenic acid than for other o-diphenols such as
      (+)-catechin, (-)-epicatechin and 4-methylcatechol, and the enzyme lacked both
      cresolase activity and p-diphenol oxidase activity. The Km value for the enzyme
      was found to be 122 microM toward chlorogenic acid. The purified enzyme had far
      less thermal stability than the enzyme of the plastid fraction. Diethyl
      dithiocarbamate, sodium azide, o-phenanthroline and sodium fluoride markedly
      inhibited the enzyme activity.

PMID- 1369068
TI  - In vivo and in vitro pheromonotropic activity of two locustatachykinin peptides
      in Bombyx mori.

PMID- 1369070
TI  - Isolation and synthesis of a new bio-antimutagen, petasiphenol, from scapes of
      Petasites japonicum.
AB  - A new bio-antimutagen, petasiphenol [3-(3,4-dihydroxyphenyl)-2-oxopropyl
      caffeate] (1) was isolated from scapes of Petasites japonicum (AD50 = 95
      micrograms/ml against UV-induced mutagenic E. coli WP2 B/r Trp-. Petasiphenol (1)
      and its isomer (2) were synthesized. The activity of 1 was observed in the
      presence of soybean oil (glyceride), although the isomer (2) did not show any
      activity in doses up to 300 micrograms/ml.

PMID- 1369071
TI  - Uncoupling action of antibiotic sporaviridins with rat-liver mitochondria.
AB  - The effects of the glycoside antibiotic sporaviridins (SVDs) on oxidative
      phosphorylation of rat-liver mitochondria were examined. SVDs released state 4
      respiration, dissipated transmembrane electrical potential, and accelerated
      ATPase activity. These facts demonstrated that SVDs are potent uncouplers of
      oxidative phosphorylation. During the uncoupling caused by SVDs, large amplitude
      swelling and oxidation of intramitochondrial NAD(P)H occurred, suggesting that
      SVDs greatly enhanced nonspecific permeability of the inner mitochondrial
      membrane. It is suggested that the uncoupling action of SVDs might be caused by
      dissipation of proton electrochemical potential due to an increase in the
      permeability of inner mitochondrial membrane.

PMID- 1369073
TI  - Hyperexpression and analysis of choB encoding cholesterol oxidase of
      Brevibacterium sterolicum in Escherichia coli and Streptomyces lividans.
AB  - We examined the expression of choB, encoding cholesterol oxidase of
      Brevibacterium sterolicum ATCC 21387, in Escherichia coli JM105 and Streptomyces
      lividans TK23 using various deletion DNA fragments within the 5'-flanking region.
      The enzyme activity could be detected intracellularly in E. coli only when the 5'
      flanking region was reduced to less than 256-bp and choB was transcribed by the
      lac promoter. A large amount of the enzyme were produced as inactive inclusion
      bodies when ChoB protein was fused with the NH2-terminal portion of LacZ protein.
      In contrast, choB with more than 256-bp of the 5'-flanking region was efficiently
      expressed in S. lividans TK23, and about 85 times as much of the active enzyme
      (170 U/ml) was secreted into the culture filtrate as with B. sterolicum in flask
      culture. These results suggest that the promoter of choB exist within 256-bp of
      the 5'-flanking region and can be efficiently recognized by the RNA polymerase of
      S. lividans. The characteristics of the enzyme purified from the culture filtrate
      of the S. lividans transformant and that of B. sterolicum were identical although
      the NH2-terminal amino acid sequence of the enzyme from the S. lividans
      transformant was 6 amino acids shorter than that from B. sterolicum.

PMID- 1369072
TI  - Conversion of dethiobiotin to biotin in cell-free extracts of Escherichia coli.
AB  - We constructed the plasmid pTTB151 in which the E. coli bioB gene was expressed
      under the control of the tac promoter. Conversion of dethiobiotin to biotin was
      demonstrated in cell-free extracts of E. coli carrying this plasmid. The
      requirements for this biotin-forming reaction included fructose-1,6-bisphosphate,
      Fe2+, S-adenosyl-L-methionine, NADPH, and KCl, as well as dethiobiotin as the
      substrate. The enzymes were partially purified from cell-free extracts by a
      procedure involving ammonium sulfate fractionation. Our results suggest that an
      unidentified enzyme(s) besides the bioB gene product is obligatory for the
      conversion of dethiobiotin to biotin.

PMID- 1369074
TI  - Purification and some properties of a Haim-sensitive alpha-amylase from newly
      isolated Bacillus sp. No. 195.
AB  - Newly isolated Bacillus sp. No. 195 produced an extracellular alpha-amylase
      sensitive to Haim which was found to inhibit specifically animal alpha-amylases.
      The enzyme was purified easily by two steps of starch adsorption and gel
      filtration using Sephacryl S-200. The purified enzyme, which showed a single band
      on native-PAGE or SDS-PAGE, had a molecular weight of 60,000 as judged on SDS
      PAGE. The optimum pH value for activity and the isoelectric point were around 7.0
      and 4.5, respectively. The sensitivity of the amylase to Haim was similar to that
      of animal amylase rather than bacterial amylase. It was suggested that a Haim
      amylase complex might be formed at the molar ratio of 1:1. The amino acid
      sequence F-S-W similar to the triplet F-E-W highly conserved among alpha-amylases
      sensitive to proteinaceous inhibitors, such as Hoe 467-A or Haim, was found in
      the amino-terminal part of the No. 195 amylase.

PMID- 1369075
TI  - Purification and characterization of a DNA-dependent RNA polymerase from
      Pseudomonas putida.
AB  - DNA-dependent RNA polymerase (EC 2.7.7.6) was purified from Pseudomonas putida.
      The enzyme had the typical composition of beta',beta,alpha, and sigma subunits of
      eubacterial RNA polymerases. The molecular masses of the subunits were 156,000
      Da, 151,000 Da, 87,000 Da, and 42,000 Da, respectively, as measured by
      polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The
      NH2-terminal amino acid residues of the alpha subunit had a marked homology with
      those of the alpha subunit of Escherichia coli RNA polymerase. The enzyme
      activity was dependent on ribonucleoside triphosphates, Mg2+, and a DNA template,
      and was inhibited in vitro by rifampicin. The enzyme activity was maximal in the
      presence of 10 mM MgCl2. In an in vitro transcription assay using the tac
      promoter-controlled DNA as a template, the RNA polymerase of P. putida initiated
      transcription at the same site as that of E. coli.

PMID- 1369076
TI  - Synthesis of (+/-)-homosarkomycin and (+/-)-rosaprostol.

PMID- 1369077
TI  - Isolation and primary structure of proteinase inhibitors from Erythrina variegata
      (Linn.) var. Orientalis seeds.
AB  - The Kunitz-type trypsin inhibitors, ETIa and ETIb, and chymotrypsin inhibitor ECI
      were isolated from the seeds of Erythrina variegata. The proteins were extracted
      from a defatted meal of seeds with 10 mM phosphate buffer, pH 7.2, containing
      0.15 M NaCl, and purified by DEAE-cellulose and Q-Sepharose column
      chromatographies. The stoichiometry of trypsin inhibitors with trypsin was
      estimated to be 1:1, while that of chymotrypsin inhibitor with chymotrypsin was
      1:2, judging from the titration patterns of their inhibitory activities. The
      complete amino acids of the two trypsin inhibitors were sequenced by protein
      chemical methods. The proteins ETIa and ETIb consist of 172 and 176 amino acid
      residues and have M(r) 19,242 and M(r) 19,783, respectively, and share 112
      identical amino acid residues, which is 65% identity. They show structural
      features characteristic of the Kunitz-type trypsin inhibitor (i.e., identical
      residues at about 45% with soybean trypsin inhibitor STI). Furthermore, the
      trypsin inhibitors show a significant homology to the storage proteins, sporamin,
      in sweet potato and the taste-modifying protein, miraculin, in miracle fruit,
      having about 30% identical residues.

PMID- 1369078
TI  - Purification and characterization of a thermostable carboxypeptidase
      (carboxypeptidase Taq) from Thermus aquaticus YT-1.
AB  - A thermostable carboxypeptidase, which we named carboxypeptidase Taq, was
      purified from Thermus aquaticus YT-1 and characterized. The molecular weight of
      the enzyme was estimated to be about 56,000 and 58,000 on SDS-polyacrylamide gel
      electrophoresis and gel filtration, respectively, indicating that the enzyme has
      a monomeric structure. The optimum pH of the enzyme was 8.0, and the optimum
      temperature for the reaction was 80 degrees C. The enzyme activity was dependent
      on cobalt ion and was inhibited by metal-chelating reagents, indicating that the
      enzyme is a metalloenzyme. The enzyme had high thermostability independent of
      cobalt ion; about 90% of its activity remained even after treatment at 80 degrees
      C for 5 h. The enzyme showed broad substrate specificity, although proline at the
      C-terminus of peptides was not cleaved. The enzyme released amino acids
      sequentially from the C-terminus.

PMID- 1369080
TI  - Calcium requirement for protoplast transfection mediated by polyethylene glycol
      of Lactobacillus casei by PL-1 Phage DNA.
AB  - The effects of some divalent cations on protoplast transfection mediated by
      polyethylene glycol of Lactobacillus casei ATCC 27092 by PL-1 phage DNA in 50 mM
      Tris-maleate buffer (pH 6.0) were investigated. The efficiency of transfection
      increased about 30 times in the presence of 10 mM Ca2+. Sr2+ increased the
      transfection rate as well, but Ba2+, Mn2+, and Mg2+ did not. Co2+ and Zn2+
      inhibited transfection. The simultaneous use of Ca2+ and Mg2+ increased the
      transfection efficiency. Impairment of transfection caused by lack of Ca2+ could
      not be reversed by the addition of Ca2+ later. A decrease in the Ca2+
      concentration to an ineffective level before transfection ended immediately
      inhibited transfection. Protoplasts were transfected with a phage adsorption
      mutant resistant to PL-1, also, and these metal ions had the same effect.
      Multiplication of phages in the transfected protoplasts was independent of the
      presence or absence of calcium ions. Calcium ions seemed to be involved in the
      entry of PL-1 DNA into the host protoplasts.

PMID- 1369079
TI  - Deletion analysis of the Taka-amylase A gene promoter using a homologous
      transformation system in Aspergillus oryzae.
AB  - The Taka-amylase A gene (amyB) of Aspergillus oryzae is induced by starch or
      maltose. The molecular mechanism of the induction was investigated using a fusion
      of the amyB promoter and the Escherichia coli uidA gene encoding beta
      glucuronidase (GUS). To identify the region responsible for high-level expression
      and regulation within the amyB promoter, a series of deletion promoters was
      constructed and introduced into the A. oryzae met locus by homologous
      recombination. Deletion of the region between -377 to -290 (the number indicates
      the distance in base pairs from the translation initiation point (+1) to the
      deletion end point) significantly reduced of the GUS activity, but slight
      reduction of the GUS activity was observed in deletions up to -377. Northern blot
      analysis showed that reduction of the GUS activity depended upon the expression
      level of the GUS gene. The region between -377 to -290 is suggested to include
      the sequence required directly for high-level expression and regulation of the
      amyB gene.

PMID- 1369081
TI  - Nucleotide sequence of the subtilisin NAT gene, aprN, of Bacillus subtilis
      (natto).

PMID- 1369082
TI  - Effects of proteases on hepatoma AH109A cells aggregated by a microbial hepatoma
      aggregation factor (HAF).

PMID- 1369083
TI  - Are you being served?

PMID- 1369084
TI  - Antibody engineering--successful affinity maturation in vitro.

PMID- 1369085
TI  - Growth factors in wound healing.

PMID- 1369086
TI  - Using microorganisms for bioremediation: the barriers to implementation.

PMID- 1369087
TI  - Monoclonal and engineered antibodies for human parenteral clinical use:
      regulatory considerations.

PMID- 1369088
TI  - Biotechnology of the Archaea.
AB  - The Archaea, designated since 1979 as a separate Super-Kingdom (the highest
      taxonomic order), are a highly novel group of microorganisms which look much like
      bacteria but have many molecular and genetic characteristics that are more
      typical of eukaryotes. These unusual organisms can be conveniently divided
      according to their 'extreme' environmental niche, into three broad phenotypes:
      the thermophiles, methanogens and extreme halophiles. Each group has unique
      biochemical features which can be exploited for use in the biotechnological
      industries. The extreme molecular stability of thermophile enzymes, the novel C1
      pathways of the methanogens and the synthesis of organic polymers by some
      halophiles are all currently or potentially valuable examples of the
      biotechnology of the Archaea.

PMID- 1369089
TI  - Genetic engineering of beta-lactam antibiotic biosynthetic pathways in
      filamentous fungi.
AB  - Recombinant DNA technology has facilitated a rapid increase in our knowledge of
      beta-lactam antibiotic biosynthesis. Using the tools of this technology, beta
      lactam biosynthetic genes and proteins have been characterized at the molecular
      level, cephalosporin-C production has been improved, new beta-lactams produced,
      and novel beta-lactam biosynthetic pathways have been constructed.

PMID- 1369090
TI  - Metabolic response to treatment with cold, paraquat, or 3-amino-1,2,4-triazole in
      leaves of winter wheat.
AB  - We treated leaves of winter wheat (Triticum aestivum L.) with cold, paraquat, or
      3-amino-1,2,4-triazole and compared the responses. We assayed the activities of
      glucose-6-phosphate dehydrogenase, catalase, dehydroascorbate reductase and
      ascorbate free radical reductase and levels of hydrogen peroxide, glucose-6
      phosphate, fructose-6-phosphate, ascorbate, dehydroascorbate, reduced and
      oxidized glutathione. With any of the three treatments, contents of cellular
      peroxides and hexose phosphates were raised. The content of ascorbate was lowered
      markedly by paraquat treatment, which produces active oxygen species, whereas
      such a decrease did not occur in other two treatments. When the plants were
      treated with 3-amino-1,2,4-triazole, which is a specific inhibitor of catalase,
      the content of oxidized glutathione increased severalfold. The glucose-6
      phosphate dehydrogenase activity increased with all three treatments, but it
      decreased after glyphosate treatment, which does not stimulate the formation of
      peroxides. The activities of catalase and dehydroascorbate reductase were
      increased by the treatment of cold and paraquat, while 3-amino-1,2,4-triazole did
      not affect the dehydroascorbate reductase activity. The activity of ascorbate
      free radical reductase increased after treatment by paraquat only.

PMID- 1369091
TI  - Characterization of membrane-bound spermidine dehydrogenase of Citrobacter
      freundii.
AB  - Spermidine dehydrogenase found in the membrane fraction of Citrobacter freundii
      IFO 12681 was solubilized with Triton X-100 and further purified to homogeneity.
      The properties of the membrane enzyme were almost identical to those obtained
      from the soluble fraction of the organism with respect to molecular and catalytic
      properties. Thus, binding properties of the enzyme to the bacterial membrane were
      checked. The ratio of enzyme activity found in the soluble fraction to the
      membrane fraction was dependent on salt concentration during cell disruption. A
      hydrophobic interaction was largely involved in anchoring the enzyme to the
      membrane fraction. Purified spermidine dehydrogenase from the soluble fraction
      was readily adsorbed into the membrane fraction in the presence of salt.
      Spermidine dehydrogenase appeared to be a membrane-bound enzyme localized in the
      cytoplasmic membranes in a manner that makes a partial release of the enzyme
      possible during mechanical cell disruption. When spermidine oxidation was done
      with the resting cells of C. freundii, a stoichiometric formation of two reaction
      products, 1,3-diaminopropane and gamma-aminobutyraldeyde, was observed without
      any lag time. These facts indicate that the enzyme is localized on the outer
      surface of the cytoplasmic membranes or in the periplasmic space of the organism.

PMID- 1369092
TI  - Isolation and genetic analysis of an Agrobacterium tumefaciens avirulent mutant
      with a chromosomal mutation produced by transposon mutagenesis.
AB  - A transposon 5 (Tn5) insertion was introduced into the genome of A. tumefaciens
      (A-208 strain harboring a nopaline type Ti-plasmid) using a conjugative pJB4JI
      plasmid containing Tn5. Five thousand transconjugants were assayed for virulence
      on carrot (Daucus carota L.) disks; 54 isolates were avirulent or very
      attenuated. The cellular localization (plasmid or chromosome) of the Tn5
      insertion in those isolates were identified by Southern hybridization analysis.
      An avirulent mutant (B-90 strain) with the Tn5 insertion in the chromosome was
      selected and characterized. The mutant had the same growth rate as that of the
      parent strain in L-broth. The mutant and the parent strain had similar attachment
      ability to carrot root cells. Tn5 was inserted into one site of the chromosome.
      The wild-type target chromosomal region (1281 base pairs) was cloned and
      sequenced. An open reading frame (ORF) consisting of 395 base pairs was
      identified. The wild-type DNA fragment (1.6 kb) containing the ORF introduced
      into B-90 strain complemented the avirulent phenotype of the strain. A soluble
      protein was predicted from the ORF. The Tn5 was inserted near the 3'-terminal of
      the ORF. Homology search of this ORF found no significant homology to known genes
      and proteins. Thus, the ORF identified in this paper seems to be a new
      chromosomal virulence gene of A. tumefaciens.

PMID- 1369093
TI  - Highly probable active site of the sweet protein monellin.
AB  - The sweet protein monellin consists of two noncovalently associated polypeptide
      chains, the A chain of 44 amino acid residues and the B chain of 50 residues.
      Synthetic monellin is 4000 times as sweet as sucrose on a weight basis, and the
      native conformation is essential for the sweet taste. Knowledge of the active
      site of monellin will provide important information on the mode of interaction
      between sweeteners and their receptors. If the replacement of a certain amino
      acid residue in monellin removes the sweet taste, while the native conformation
      is retained, it may be concluded that the position replaced is the active site.
      Our previous replacement studies on Asp residues in the A chain did not remove
      the sweet taste. The B chain contains two Asp residues at positions 7 and 21,
      which were replaced by Asn. [AsnB21]Monellin and [AsnB7]monellin were 7000 and 20
      times sweeter than sucrose, respectively. The low potency of the [AsnB7]monellin
      indicates that AspB7 participates in binding with the receptor. AspB7 was then
      replaced by Abu. [AbuB7]Monellin was devoid of sweetness, and retained the native
      conformation. AspB7 is located at the surface of the molecule (Ogata et al.).
      These results suggest that Asp7 in the B chain is the highly probable active site
      of monellin.

PMID- 1369094
TI  - Purification and primary structure of proteinous alpha-amylase inhibitor from
      Streptomyces chartreusis.
AB  - A new polypeptide inhibitor, AI-409, that inhibits human salivary alpha-amylase,
      was purified from a fermentation broth of Streptomyces chartreusis strain No.
      409. This protein consists of a single-chain polypeptide of 78 amino acid
      residues, and includes two disulfide bridges. The primary structure of AI-409 and
      the locations of the disulfide bridges were identified by enzymatic digestion and
      the automatic Edman technique. Enzymatic digestion was done with trypsin,
      carboxypeptidase Y, and chymotrypsin. One of the disulfide bridges was between
      Cys(10) and Cys(26), and the other between Cys(44) and Cys(71).

PMID- 1369095
TI  - Overproduction of biologically-active human nerve growth factor in Escherichia
      coli.
AB  - A gene coding for human nerve growth factor (hNGF) was constructed for expression
      under control of the trp promoter in E. coli. The plasmid pTRSNGF contained a
      synthetic hNGF gene fused, in frame, to the region encoding the beta-lactamase
      signal peptide. The plasmid pTRLNGF contained the same coding sequence as hNGF
      attached downstream from the N-terminal fragment of the trp L gene. E. coli cells
      harboring pTRSNGF produced an amount of hNGF constituting 4% of the total
      cellular protein, and removed the beta-lactamase signal peptide. The mature
      protein hNGF was biologically active in the PC12h bioassay for neurite outgrowth.
      This biological activity was comparable to that of authentic mouse NGF. E. coli
      cells harboring pTRLNGF produced an amount of fusion protein hNGF constituting
      25% of the total cellular protein. Although the fusion protein hNGF formed
      inclusion bodies in cells, dissolved fusion protein hNGF was active in neurite
      outgrowth from PC12h cells.

PMID- 1369096
TI  - Primary structure of a base non-specific and adenylic acid preferential
      ribonuclease from the fruit bodies of Lentinus edodes.
AB  - The complete primary structure of a base non-specific and adenylic acid
      preferential RNase (RNase Le2) from the fruit bodies of Lentinus edodes was
      analyzed. The sequence was mostly determined by analysis of the peptides
      generated by V8 protease digestion and BrCN cleavage (including alpha
      chymotryptic, and V8 protease digest of BrCN fragments). It consists of 239 amino
      acid residues. The molecular weight is 25831. The location of 10 half cystine
      residues were almost superimposable on those of known fungal RNases of the RNase
      T2 family. The sequence homologies between RNase Le2 and four known fungal RNases
      of the RNase T2 family, RNase T2, RNase M, RNase Trv, and RNase Rh, are 102, 103,
      109, and 74, respectively. The homologous sequences are concentrated around the
      three histidines, which are supposed to form the active site of RNase T2 family
      RNases.

PMID- 1369097
TI  - Effects of L-156,602, a C5a receptor antagonist, on mouse experimental models of
      inflammation.
AB  - L-156,602, a C5a receptor antagonist, was found as an immunosuppressant with
      preferential effects on delayed-type hypersensitivity (DTH) in our screening
      program and it was shown that L-156,602 suppressed the efferent phase of DTH.
      Here, we tested its effects on experimental models of inflammation induced in
      mice. L-156,602 did not suppress serotonin- and carrageenan- induced inflammation
      while it completely suppressed concanavalin A-induced inflammation 4 h after
      elicitation. The inflammation appeared 24 h after the elicitation with
      concanavalin A and it was significantly suppressed by L-156,602. Muramyl
      dipeptide (MDP)-induced acute joint inflammation was also significantly
      suppressed by L-156,602. These results demonstrated the unique immunomodulating
      properties of L-156,602 in mouse experimental models of inflammation.

PMID- 1369098
TI  - Ion spray mass spectra of native and recombinant streptococcal antitumor
      proteins.

PMID- 1369099
TI  - Molecular cloning and structure of the gene for esterase from a thermophilic
      bacterium, Bacillus stearothermophilus IFO 12550.

PMID- 1369100
TI  - Effect of Pluronic F-68 on the mechanical properties of mammalian cells.
AB  - The mechanical properties of TB/C3 hybridoma cells taken from a continuous
      culture were measured by micromanipulation. The culture conditions were constant
      except for the presence or absence of Pluronic F-68 in the medium. It was found
      that the mean bursting membrane tension and the mean elastic area compressibility
      modulus of the cells were significantly greater (60% and 120%, respectively) in a
      medium with 0.05% (w/v) Pluronic F-68 compared to that without Pluronic. Pluronic
      F-68 therefore affected the strength of the membranes when the cells were exposed
      to it for a long period of time, i.e., in culture. The short-term effect of
      Pluronic F-68 on cell strength was also tested by its addition at various levels
      up to 0.2% (w/v) immediately before the mechanical property measurements. The
      resulting cell strength depended on the Pluronic concentration, but a significant
      short-term effect could only be detected above a threshold of 0.1% (w/v).
      Previous reports on the effect of Pluronic F-68 on animal cell culture are
      evaluated in the light of these observations.

PMID- 1369101
TI  - Humans and viruses determine the nature of virus vaccine production processes.
AB  - Vaccine production processes result from the interaction between humans with a
      particular cell and virus system. The factors that control progress lie not only
      in the nature of the virus and animal cell but also in the history of the
      environment in which the process is to be developed. This latter constraint
      strongly influences the nature of the technical process that is chosen for the
      production of the vaccine rather than the achievement of efficiency based on one
      or other of the many possible engineering parameters of the virus production
      process. In addition to this it is also clear that we have much to learn about
      the production of viruses from animal cells in culture and that we may be aided
      by changing our present paradigm of the "virus as a cellular enemy" to that of
      the "viruses are the cell's best friend".

PMID- 1369102
TI  - Interleukin-6 is antiproliferative to a mouse hybridoma cell line and promotive
      for its antibody productivity.
AB  - Monoclonal antibody production by hybridoma cells at moderately slowed growth
      states would be favorable for commercial scale production since cells can devote
      their resources to performing the differentiated function, immunoglobulin
      production. We found that a purified recombinant human interleukin-6, which had
      been reported to support or stimulate proliferation of B cell
      hybridoma/plasmacytoma cells, suppressed growth of a hybridoma cell line in serum
      free medium. In the presence of the interleukin, the growth-suppressed cells were
      viable for remarkably long periods in batch culture, and after removal of the
      interleukin from the culture medium, they started to proliferate at their normal
      growth rate. As the concentration of the interleukin increased in the culture,
      the growth rate decreased and the specific antibody productivity (antibody
      production rate per cell) increased to 5-fold of control at 10 U ml-1 (2 ng ml-1)
      of the interleukin.

PMID- 1369103
TI  - Continuous production of large amounts of monoclonal immunoglobulins in hollow
      fibers using protein-free medium.
AB  - The performance of a protein-free medium was compared in culture flasks with a
      serum-supplemented medium and with a serum free medium in terms of cell growth
      and monoclonal antibody production by a murine hybridoma. We present results of
      continuous production in hollow fiber culture systems using serum-free medium and
      protein-free medium. In protein-free medium, it has been possible to produce
      large quantities of monoclonal antibody with a productivity similar to that
      obtained in serum-free medium. After a two steps purification process, monoclonal
      antibodies were characterized by SDS-PAGE, High Performance Size Exclusion
      Chromatography and Free Solution Capillary Electrophoresis. SDS-PAGE and high
      performance chromatography analysis have showed that purified monoclonal
      antibodies produced in serum-free medium or protein-free medium were similar.
      Furthermore, Capillary Electrophoresis characterization revealed that both MAbs
      were constituted by three isoforms with equivalent electrophoretic mobilities.

PMID- 1369104
TI  - Characterization of macrophage cell line A640-BB-2: A640-BB-2 resembles
      peritoneal exudate macrophages in cell morphology, tumor cell recognition,
      responsiveness to immunomodulator OK-432 and lysosomal enzyme activity.
AB  - Characteristics of mouse macrophage (MP) cell lines A640-BB-2, J774.1 and P388D1
      and mouse peritoneal exudate MPs were studied and compared in cell morphology,
      ability to recognize tumor cells in the presence and absence of OK-432 known to
      activate MPs, and in lysosomal enzyme activity. In A640-BB-2 cells and exudate
      MPs, cell surfaces showed a few ridge-like processes and microvilli; spontaneous
      cytotoxicity was moderate against tumor target L929, and little or absent against
      targets SV3T3, B-16 and U937; and lysosomal enzyme activity of nonspecific
      esterase, acid phosphatase, and beta-glucuronidase was high. After culture in the
      presence of OK-432, A640-BB-2 cells and exudate MPs showed more extensive
      spreading with larger surface areas and with increased numbers of ridge-like
      processes and microvilli, and their cytotoxicity against target L929 became more
      extensive. The stable soluble factor did not participate in the mechanism of
      cytotoxicity against target L929 mediated by A640-BB-2 cells and exudate MPs.
      J774.1 and P388D1 cells were different from exudate MPs in cell morphology and
      ability to recognize tumor cells when cultured either with or without OK-432, and
      in lysosomal enzyme activity. A640-BB-2 cells seem to be useful in studying MP
      tumor cell interaction and MP activation, and in detecting the trace biological
      activating factor of MPs.

PMID- 1369105
TI  - Simulation of an iterative learning control system for fed-batch cell culture
      processes.
AB  - This paper describes an iterative learning control scheme for fed-batch operation
      where repetitive trajectory tracking tasks are required. The proposed learning
      strategy is model-independent, and it takes advantage of the repetitive feature
      of system operations with a certain degree of intelligence and requires only
      small size of dynamic database for the learning process. The convergence of the
      learning process is proven. An example of simultaneously tracking two predefined
      trajectories by iterative learning control with two control inputs is given to
      illustrate the methodology. Satisfactory performance of the learning system can
      be observed from the simulation results.

PMID- 1369106
TI  - Chemically defined medium for the production of biologically active substances of
      CHO cells.
AB  - A recombinant CHO cell line (GT19) secreting a high level of human growth hormone
      (hGH) was constructed with amplification of the introduced hGH gene. The cells
      grew well in the alpha MEM medium supplemented with 5% dialyzed fetal calf serum
      (dFCS), but not with less than 1% dFCS. Therefore we examined various medium
      components and obtained an improved medium which supported cell growth at low
      serum concentrations. The production of hGH by the cells was also enhanced in
      this medium.

PMID- 1369107
TI  - Bioquest Limited.

PMID- 1369108
TI  - Agen Biomedical Limited.

PMID- 1369109
TI  - TECRA diagnostics.

PMID- 1369110
TI  - Biotech International Ltd.

PMID- 1369111
TI  - Trace Scientific.

PMID- 1369112
TI  - Genetic manipulation of milk proteins and its consequences for the dairy
      industry.
AB  - Genetic selection of cattle by selective breeding patterns dates back to
      prehistoric times and has resulted in the diversity of breeds we see today.
      Selection in New Zealand has been for fat production earlier in the century, and
      more recently for protein production as well as fat. There is a lot of interest
      today in the naturally occurring variants of the milk proteins, as these can
      confer interesting differences in the molecular behaviour of the proteins as well
      as being correlated with compositional differences in the milk. Genetic
      modification holds great promise for the future in the dairy industry, but
      present constraints due to cost, lack of basic knowledge, and difficulty in
      producing genetically-modified calves, mean that only the biopharmaceutical area
      is likely to be affected in the near future. Coupled to this is an apparent lack
      of acceptance of food from genetically-modified animals by consumers. It will
      therefore need a change in public attitude as well as some development in science
      and technology before dairy products from genetically modified cattle become a
      commercial reality.

PMID- 1369114
TI  - Examination of Federal Government response to recommendations of House of
      Representatives Standing Committee on Industry, Science and Technology's Inquiry
      into GMOs.

PMID- 1369113
TI  - Intellectual property reform and administration.

PMID- 1369115
TI  - Mammalian sex-determining genes.
AB  - The recent cloning of the Y-linked sex-determining gene SRY has ended one of the
      most notorious gene hunts in mammalian molecular genetics. Attention has now been
      turned to characterizing this gene further and studying how it acts as a switch
      in the choice of male or female developmental pathways.

PMID- 1369116
TI  - The human genetic map.
AB  - The introduction of new technology and increased effort from around the world is
      driving the completion of the human gene map. In parallel with the creation of
      the map, we are beginning to see the bio-medical benefits that are a direct
      consequence of learning more about our own genome.

PMID- 1369117
TI  - DNA structure, mutations, and human genetic disease.
AB  - The etiology of fragile X syndrome, myotonic dystrophy and Kennedy's disease has
      been attributed to the massive expansion of triplet repeat DNA sequences. This
      review details the relationships between the structural diversity of DNA, its
      secondary structure or DNA-directed mutagenesis, and the expansion of triplet
      repeats.

PMID- 1369118
TI  - Molecular cytogenetics: diagnosis and prognostic assessment.
AB  - This review describes molecular cytogenetic techniques for detection and
      characterization of genetic aberrations associated with human disease. The
      techniques of fluorescence in situ hybridization, primed in situ labeling and
      comparative genome hybridization are described, as are probes for repeated
      sequences, whole chromosomes and specific loci. Also reviewed are applications of
      these technologies to pre- and neonatal diagnosis and to the characterization of
      human malignancies.

PMID- 1369119
TI  - Relevance of genomic imprinting to human diseases.
AB  - The existence of functional differences between parts of the maternal and
      paternal genome has been demonstrated. The control of gene expression through
      genomic imprinting plays a significant role in normal developmental processes in
      mammals and is also instrumental in several human pathological conditions.

PMID- 1369120
TI  - Transgenic animal models of cardiovascular disease.
AB  - Transgenic experimentation has become a crucial part of hypertension and
      atherosclerosis research, and is growing more important in several other areas of
      cardiovascular disease. It has recently made a particular contribution to
      understanding the role of the renin-angiotensin system in controlling
      hypertension. The study of blood pressure regulation, cardiac hypertrophy,
      atherogenesis and thrombosis are also benefiting from the transgenic approach.

PMID- 1369121
TI  - Immunotherapy of AIDS.
AB  - The immunotherapy of AIDS encompasses a broad range of therapeutic possibilities.
      A number of stimulating and immunomodulating agents have been tried without any
      overt success. More recently, passive immunotherapy of AIDS using donated plasma
      and active therapeutic vaccine procedures have been reported. A number of
      clinical and laboratory observations together with preliminary results of
      clinical trials suggest that post-infection vaccines may be able to delay
      progression to disease in some individuals.

PMID- 1369122
TI  - Oligonucleotide therapy.
AB  - Rapid progress in oligonucleotide therapeutics has continued over the past year
      as major programs established in the past four years have grown and begun to be
      productive. Important advances were reported in the medicinal chemistry of
      oligonucleotides and in understanding their pharmacodynamic properties.
      Significant progress was made in understanding the pharmacokinetic and
      toxicologic properties of first generation analogs, particularly
      phosphorothioates and one oligonucleotide, ISIS 2105, entered clinical trials.
      Additionally, combinatorial approaches designed to identify oligonucleotides that
      may bind to a variety of targets were reported.

PMID- 1369123
TI  - Therapeutic immunosuppression of T cells.
AB  - Current immunosuppressive therapy carries a range of unwanted side effects, and
      tends to penalize the whole immune system. It is desirable to develop therapies
      that are more selective for antigen-reactive cells. As T lymphocytes use a wide
      range of surface receptors to interact with antigen-bearing cells and with each
      other, much interest is devoted to trying to develop agents that selectively
      block the interaction of these receptors with their ligands, and others that
      could be used to reprogram the immune system so that it might become tolerant to
      the antigens rather than attack them.

PMID- 1369124
TI  - Families of twelve transmembrane domain transporters.
AB  - Several functionally distinct families of transport proteins share the general
      structural motif of twelve transmembrane domains. The number of membrane proteins
      known to possess this common feature continues to expand with the cloning of
      transporters for various neurotransmitters, nucleosides, osmolytes and basic
      amino acids, in addition to the previously defined families of facilitative and
      sodium-driven sugar transporters.

PMID- 1369126
TI  - Mammalian gene studies.

PMID- 1369125
TI  - Alzheimer's disease: transgenic models to test new chemicals and pharmaceuticals.
AB  - Alzheimer's disease is the most common form of senile dementia and is predicted
      to become even more prevalent as the proportion of elderly in the population
      increases over the next few decades. As yet, there are no effective treatments
      for the disorder. A major limitation to identifying new drugs and therapeutic
      targets for Alzheimer's disease has been the absence of an animal model
      displaying typical Alzheimer's pathology. Transgenic technology is now providing
      a powerful new approach for the development of animal models of Alzheimer's
      disease.

PMID- 1369127
TI  - Pharmaceutical applications.

PMID- 1369128
TI  - Purification and characterization of nitrilase responsible for the
      enantioselective hydrolysis from Acinetobacter sp. AK 226.
AB  - A nitrilase was purified, apparently to homogeneity, from a cell extract of
      Acinetobacter sp. AK 226, which converts racemic 2-(4'
      isobutylphenyl)propionitrile (Ibu-CN) to S-(+)-2-(4'-isobutyl-phenyl)propionic
      acid (S-(+)-ibuprofen). The molecular weight of the native enzyme was estimated
      as 580,000 upon gel filtration. The nitrilase hydrolyzed many kinds of nitrile
      compounds such as aliphatic, aromatic, and heterocyclic mononitriles or
      dinitriles. The amino-terminal amino acids were sequenced and found to be partly
      homologous to a nitrilase from Klebsiella pneumoniae subsp. ozanae. The purified
      enzyme had a pH optimum of 8.0 and a temperature optimum of 50 degrees C. The
      enzyme was not affected by chelating reagents, carbonyl reagents, reductants,
      most metal ions, or thiol reagents except silver ion, p-chloromercuribenzoate,
      and phenylmercuribenzoate. The reaction with racemic Ibu-CN resulted in the
      preferential production of S-(+)-ibuprofen, demonstrating that the nitrilase is
      highly enantioselective to S-(-)-Ibu-CN. In fact, the enzyme showed a 180-fold
      higher activity for racemic Ibu-CN than that for R-(+)-Ibu-CN.

PMID- 1369129
TI  - Genome projects revisited.

PMID- 1369130
TI  - Progress in developing methylotrophic yeasts as expression systems.

PMID- 1369131
TI  - Marker gene removal: a practical necessity?

PMID- 1369132
TI  - Cytokine expression by recombinant viruses--a new vaccine strategy.

PMID- 1369133
TI  - Mass measurement at high molecular weight--new tools for biotechnologists.
AB  - It has long been possible to analyse small molecules accurately and reproducibly
      by mass-spectrometric techniques. Two new techniques extend the application of
      mass spectrometry to proteins and other biopolymers of high molecular mass. The
      accuracy, sensitivity and resolving power of these new methods permits the
      detection of minor, but biologically significant protein modifications.

PMID- 1369134
TI  - Designer dyes: 'biomimetic' ligands for the purification of pharmaceutical
      proteins by affinity chromatography.
AB  - Affinity chromatography has been extensively refined over the past few years to
      meet the more stringent criteria being placed on recombinant proteins as
      therapeutic products. New developments in the design of selective and stable
      ligands for affinity chromatography are establishing the technique as a routine
      tool in process-scale protein purification. Exploitation of sophisticated
      molecular modelling techniques in conjunction with binding and crystallographic
      studies has permitted the design of new, highly selective 'biomimetic' ligands
      for the target proteins.

PMID- 1369136
TI  - Safe biotechnology (4). Recommendations for safety levels for biotechnological
      operations with microorganisms that cause diseases in plants.
AB  - The Working Party on Safety in Biotechnology of the European Federation of
      Biotechnology has proposed a classification of microorganisms that cause diseases
      in plants. In this paper appropriate safety levels are proposed for these classes
      of microorganisms in order to ensure that research, development and industrial
      fermentation work with plant pathogens will limit the risk of outbreaks of
      diseases in crops that could result from work with such microorganisms when they
      are cultivated in laboratories, glasshouses and biotechnology installations.

PMID- 1369135
TI  - Microbes and microbial enzymes for cyanide degradation.
AB  - Cyanide is an important industrial chemical produced on a grand scale each year.
      Although extremely toxic to mammalian life, cyanide is a natural product
      generated by fungi and bacteria, and as a result microbial systems have evolved
      for the degradation of cyanide to less toxic compounds. The enzymes which utilize
      cyanide as a substrate can be categorized into the following reaction types:
      substitution/addition, hydrolysis, oxidation, and reduction. Each of these
      categories is reviewed with respect to the known biochemistry and feasibility for
      use in treatment of cyanide containing wastes.

PMID- 1369137
TI  - Continuous high-cell-density fermentation of the ciliated protozoon Tetrahymena
      in a perfused bioreactor.
AB  - An efficient method of growing the protozoon Tetrahymena to high cell densities
      in a 2-1 bioreactor is described. The first phase of the fermentation is a batch
      phase with minimum generation times (1.4 h). During the next phase medium is
      exchanged continuously using a perfusion module based on microporous hollow
      fibres while cell are retained. Compared to standard batch fermentations of this
      organism 30- to 40-fold higher cell concentrations and dry weights were achieved
      routinely. A maximum cell concentration of 2.2 x 10(7) cells/ml and a dry weight
      of 54 g/l have been obtained. As estimated from isocitrate dehydrogenase activity
      in the culture medium, no cell damage occurred even at high agitation rates. In
      addition, the cells remained viable for several weeks. Temporal limitation of the
      process was due to a decrease in the perfusion rate caused by blocking of the
      membranes. By X-ray microprobe analysis calcium phosphate depositions were
      detected in the pores of the clogged hollow-fibre membranes. However, even a T.
      pyriformis strain possessing mucocysts, dense core secretory organelles that may
      lead to early membrane clogging, was cultivated successfully for 3 weeks.
      Additionally, the consumption of nutrient protein and carbohydrates during
      fermentation was investigated and the effect of different perfusion rates and of
      glucose was studied in order to increase the efficacy of the system.

PMID- 1369138
TI  - Introduction of sulphhydryl groups into the crystalline bacterial cell surface
      layer protein from Bacillus stearothermophilus PV72 and its application as an
      immobilization matrix.
AB  - The crystalline cell surface layer (S-layer) from Bacillus stearothermophilus
      PV72 was used as a matrix for reversible immobilization of beta-D-galactosidase
      via disulphide bonds. In order to obtain an immobilization matrix stable towards
      acid, alkali and reducing agents such as dithiothreitol (DTT), the S-layer
      subunits were first cross-linked with glutaraldehyde. This was done in a way
      whereby 75% of the free amino groups remained unmodified, and then could be
      completely converted into sulphhydryl groups upon reaction with the
      monofunctional imidoester iminothiolane. After activation of the sulphhydryl
      groups with 2,2'-dipyridyldisulphide, 550 micrograms beta-D-galactosidase could
      be immobilized per milligram of S-layer protein, which corresponds to one beta-D
      galactosidase molecule [relative molecular mass (M(r)), 116,000] per two S-layer
      subunits (M(r), 130,000). At least 90% of the sulphhydryl groups from the S-layer
      protein could be regenerated for further activation by cleaving the disulphide
      bonds with DTT. In comparative studies beta-D-galactosidase was linked to
      carbodiimide-activated carboxyl groups of the S-layer protein.

PMID- 1369139
TI  - Influence of pH, nitrogen and phosphorus sources on the production of hepatitis B
      virus pre-S2 antigen by Hansenula polymorpha.
AB  - Experimental design techniques were used to study the influence of the
      composition of the culture medium on the production of hepatitis B virus pre-S2
      antigen by the methylotrophic yeast Hansenula polymorpha. pH, phosphoric acid,
      ammonium chloride and yeast extract concentrations were selected as experimental
      factors and their influence was investigated using Central Composite design
      techniques. The results indicated that antigen yield was maximized at high pH and
      in a culture medium containing both ammonium chloride and yeast extract.
      Phosphoric acid was found to have a detrimental effect on antigen production.
      This study allowed a 50% increase in antigen production in a medium in which the
      yeast extract concentration was decreased to 32 g/l. These optimal conditions
      have been confirmed with an octagonal design experiment. Moreover, it was shown
      that the antigen produced was very stable up to at least 8 days after induction
      and that the yeast extract concentration could be lowered to 22 g/l without
      appreciable effect on antigen yield. The increase in antigen production was not
      due to an increase in cell biomass, since no correlation could be found between
      these two parameters. The newly defined culture medium should allow a greatly
      increased antigen production at the fermentor level, at a lower cost and with
      minimal operational problems.

PMID- 1369140
TI  - Low-serum medium development for human diploid fibroblast microcarrier cultures.
AB  - A new medium supplement mixture, PPRF92, has been developed to enable the serial
      subculture of human diploid fibroblasts (MRC-5 cells) on microcarriers.
      Furthermore, the PPRF92 supplements enable cell growth at serum levels as low as
      1%. Through an optimization programme, the PPRF92 supplements have evolved into a
      simple mixture with the concentrations of key components at a level that makes
      the overall cost very competitive with medium containing 10% foetal bovine serum
      (FBS). Furthermore, the PPRF92 supplement mixture is most efficacious when FBS is
      replaced with the cheaper, and more widely available, adult bovine serum (ABS).
      Although medium exchange with serum is necessary in order to achieve confluence
      on microcarriers, the PPRF92 mixture is only necessary at the initiation of each
      passage. Using the medium replenishment protocol that has been developed in our
      laboratory, MRC-5 cells were successfully serially passaged through 13 bead-to
      bead transfers on microcarriers in DMEM/F12 medium enriched with the PPRF92
      supplement mixture reported here, and 1% ABS.

PMID- 1369141
TI  - Kinetic resolution of organosilicon compounds by stereoselective dehydrogenation
      with horse liver alcohol dehydrogenase.
AB  - Stereoselective dehydrogenation of three isomers of trimethylsilylpropanol was
      carried out with horse liver alcohol dehydrogenase (HLADH, EC 1.1.1.1.) and
      optically active organosilicon compounds were obtained in a water-organic solvent
      two-layer system with coenzyme regeneration. Furthermore, we examined the effects
      of the silicon atom on stereoselectivity of HLADH compared to the corresponding
      carbon compounds. Substitution of the silicon atom for the carbon atom was found
      to improve the stereoselectivity of HLADH. For example, the optical purity of the
      remaining 1-trimethylsilyl-2-propanol was higher than 99% enantiomeric excess
      (ee) at 50% conversion, whereas that of the carbon analogue was 84% ee. This
      phenomenon was probably ascribable to the bulkiness of the organosilicon
      compounds derived from their longer Si-C bond. Kinetic analysis in an aqueous
      monolayer system demonstrated that the specific properties of the silicon atom
      greatly affected the reactivity of these substrate compounds.

PMID- 1369142
TI  - Continuous production of restriction endonucleases: continuous two-stage
      cultivation with E. coli JM103; continuous cell disintegration and purification
      by affinity chromatography.
AB  - The optimization of the production of recombinant DNA-derived proteins in
      Escherichia coli was investigated. We chose restriction endonucleases EcoRI and
      EcoRV from E. coli as model proteins, despite the observation that overproduction
      can result in a toxic effect to the cells. The enzymes were expressed as fusion
      proteins consisting of protein A from Staphylococcus aureus and the desired
      enzyme in order to facilitate purification. The expression of the fusion protein
      was induced by a temperature shift using the pR promoter of phage lambda
      regulated by the repressor plasmid pRK248cI. Data from batch fermentations
      provided the basis for planning a continuous two-stage fermentation. The EcoRI
      enzyme activity was investigated as a function of the induction time after cell
      disintegration and allowed an estimation of yield of the continuous culture.
      Plasmid instability, which was only observed under continuous conditions, could
      be prevented by adding tetracycline (resistance of the repressor plasmid) to the
      medium. We established a continuous cell disintegration system and purified the
      fusion protein semicontinuously by affinity chromatography. The biological
      activity of the fusion protein was the same as the native endonuclease so there
      was no need for cleavage of the fusion protein and the product could be used
      without further processing.

PMID- 1369143
TI  - Secretory expression of a glutamic-acid-specific endopeptidase (SPase) from
      Staphylococcus aureus ATCC12600 in Bacillus subtilis.
AB  - In order to obtain a large quantity of glutamic-acid-specific endopeptidase of
      Staphylococcus aureus ATCC12600 (SPase) without cultivating its pathogenic host
      bacterium, expression plasmids enabling secretion of SPase from Bacillus subtilis
      were constructed by inserting the SPase gene into B. subtilis-Escherichia coli
      shuttle vectors. B. subtilis harbouring a simple recombinant plasmid containing
      the coding and the 5'-flanking regions of SPase in the shuttle vector pHY300PLK
      secreted 22 mg/l of SPase into the medium. As this level was lower than that of
      the natural strain (45 mg/l), we tried to increase the expression level by
      constructing a series of hybrid plasmids with the following features: (1) the
      terminator sequence of the alkaline protease gene from B. subtilis, (2) the
      promoter and the leader sequences of the alpha-amylase gene or of alkaline
      protease gene from B. amyloliquefaciens, (3) the vector pHY300PLK and the fused
      vector of pHY300PLK and pUB110. By using a variety of hybrid plasmids, the
      resulting transformants secreted SPase at levels of 33-120 mg/l. The recombinant
      SPase isolated from the medium was indistinguishable from the natural one with
      respect to its behaviour on sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis and Western blotting as well as its enzyme activity.

PMID- 1369144
TI  - Cloning and heterologous expression of a novel arylmalonate decarboxylase gene
      from Alcaligenes bronchisepticus KU 1201.
AB  - We have cloned and sequenced a DNA fragment that encodes the arylmalonate
      decarboxylase (AM-Dase) gene from Alcaligenes bronchisepticus KU 1201. The AMDase
      gene consists of an open reading frame of 720 nucleotides, which specifies a 240
      amino-acid protein of relative molecular mass (M(r)) 24734. The M(r) deduced from
      the AMDase gene is in good agreement with that of the AMDase isolated from A.
      bronchisepticus. No TATA or TTGA sequence was observed within the cloned DNA
      fragment, but the fragment was expressed in Escherichia coli by the lac promoter
      of pUC19. The enzyme produced in E. coli has the same M(r) and the same enzyme
      activity as that purified from A. bronchisepticus. Comparison of the DNA sequence
      and the deduced amino acid sequence of AMDase with available DNA and amino acid
      sequence data bases revealed that there are no significant sequence homologies.

PMID- 1369145
TI  - Selection and characterization of alpha-amylase-overproducing recombinant
      Escherichia coli containing the bacterial hemoglobin gene.
AB  - We previously reported that the presence of the bacterial (Vitreoscilla)
      hemoglobin gene enhances alpha-amylase production in recombinant Escherichia coli
      strain MK79. Using the growth of MK79 on starch as a selective method we have
      produced a mutant strain (BSC9) that produces up to four times as much alpha
      amylase as MK79. Both MK79 and BSC9 produce the most alpha-amylase (per cell and
      per milliliter) in the stationary phase; almost all of the enzyme is
      intracellular in both strains. Modification of the standard alpha-amylase assay
      increases the amount of amylase detected about sixfold. BSC9 has about five to
      nine times as many copies per cell as MK79 of the recombinant plasmid, which
      carries both the amylase and hemoglobin genes, but both strains produce about the
      same amount of hemoglobin. While MK79 respiration decreases upon going from log
      to stationary phase, BSC9 respiration increases during the same period. The two
      latter results may be of particular importance in determining the way in which
      hemoglobin enhances the production of cloned protein products in recombinant
      bacteria.

PMID- 1369146
TI  - Cloning and expression of a thermostable exo-alpha-1,4-glucosidase gene from
      Bacillus stearothermophilus ATCC12016 in Escherichia coli.
AB  - The gene coding for a thermostable exo-alpha-1,4-glucosidase (alpha-glucoside
      glucohydrolase: EC 3.2.1.20) of Bacillus stearothermophilus ATCC 12016 was cloned
      within a 2.8-kb AvaI fragment of DNA using the plasmid pUC19 as a vector and
      Escherichia coli JM109 as a host. E. coli with the hybrid plasmid accumulated exo
      alpha-1,4-glucosidase mainly in the cytoplasm. The level of enzyme production was
      about sevenfold higher than that observed for B. stearothermophilus. The cloned
      enzyme coincided absolutely with the B. stearothermophilus enzyme in its relative
      molecular mass (62,000), isoelectric point (5.0), amino-terminal sequence of 15
      residues (Met-Lys-Lys-Thr-Trp-Trp-Lys-Glu-Gly-Val-Ala-Tyr-Gln-Ile-Tyr-), the
      temperature dependency of its activity and stability, and its antigenic
      determinants.

PMID- 1369147
TI  - Purification of lipases.
AB  - Interest on lipases from different sources (microorganisms, animals and plants)
      has markedly increased in the last decade due to the potential applications of
      lipases in industry and in medicine. Microbial and mammalian lipases have been
      purified to homogeneity, allowing the successful determination of their primary
      aminoacid sequence and, more recently, of the three-dimensional structure. The X
      ray studies of pure lipases will enable the establishment of the structure
      function relationships and contribute for a better understanding of the kinetic
      mechanisms of lipase action on hydrolysis, synthesis and group exchange of
      esters. This article reviews the separation and purification techniques that were
      used in the recovery of microbial, mammalian and plant lipases. Several
      purification procedures are analysed taking into account the sequence of the
      methods and the number of times each method is used. Novel purification methods
      based on liquid-liquid extraction, membrane processes and immunopurification are
      also reviewed.

PMID- 1369148
TI  - Characterization of two differently glycosylated molecular species of yeast
      derived hepatitis B vaccine carrying the pre-S2 region.
AB  - Modified hepatitis B virus surface antigen M protein particles (HBsAg M-P31c)
      produced in yeast is mainly composed of two differently glycosylated proteins,
      GP37 and GP34. GP37 has an N-linked sugar chain and O-linked sugar chains; and
      GP34 has an N-linked sugar chain bound to the peptide backbone P31. Although M
      P31c vaccine elicits both anti-S and anti-pre-S2 antibodies, whether there are
      any differences between GP37 and GP34 in the ability to elicit these antibodies
      is still unknown. To clarify this issue, we prepared particles which were
      composed solely of GP37 or GP34 by affinity chromatography, using polymerized
      human serum albumin as a ligand and digestion with alpha-mannosidase. We also
      prepared particles composed solely of P31 by successive digestion with alpha
      manosidase and endo-beta-N-acetylglycosaminidase H. The vaccines derived from
      these three kinds of particles elicited both anti-S and anti-pre-S2 antibodies in
      mice to the same extent as the original M-P31c vaccine. These results suggest
      that the N- and O-linked sugar chains of M-P31c component proteins produced in
      the host yeast cells have no effect on the ability to elicit anti-S and anti-pre
      S2 antibodies and that there are no differences with respect to antibody response
      in mice between the two major components of M-P31c, GP37 and GP34.

PMID- 1369150
TI  - Selective protein separations using Formed-In-Place anion exchange membranes.
AB  - Anion exchange membranes prepared by adsorption of polymers on Formed-In-Place
      microfiltration substrates were formed and ion-exchange separations of solutions
      containing two proteins were determined by ion exchange membrane sequential
      separation procedures, similar to affinity membrane separation procedures.
      Representative ion exchange separation processes utilizing adsorbed poly(ethylene
      imine) (PEI) as the ion exchange membrane for the separation of the components of
      solutions containing two proteins, bovine serum albumin (BSA) and lysozyme and
      ovalbumin and lysozyme, are described. The stability of the PEI adsorbed layer,
      binding characteristics of the BSA to the membrane and purification properties of
      the procedure were determined.

PMID- 1369149
TI  - Studies on the enzymatic reduction of N-Boc-4S-amino-3-oxo-5-phenylpentanoic acid
      methylester.
AB  - The enzymatic reduction of N-Boc-4S-amino-3-oxo-5-phenylpentanoic acid
      methylester, the key intermediate in the stereoselective synthesis of a
      statinanalogue, was studied with Hansenula anomala and Hansenula silvicola. Using
      whole cells of H. anomala gives complete conversion and a diastereomeric excess
      of 88% of the desired 3S, 4S statinanalogue. The strain contains two NADPH
      dependent oxidoreductases, that can be separated by ion exchange chromatography
      or gelfiltration, yielding the 3S, 4S or 3R, 4S stereoisomers, respectively, with
      > 99% diastereomeric excess (DE). In the crude extract the 3S, 4S oxidoreductase
      is very unstable and could be purified with << 1% yield only. In contrast, H.
      silvicola, which gave poor conversions using whole cells, exhibited about 80-fold
      higher specific activity in the crude extract than H. anomala. The NADPH
      dependent oxidoreductase was purified 317-fold in 12% yield. A single enzyme of
      54 kDa reduces the substrate with 97.4% DE. Besides the statinanalogue a wide
      range of other compounds could be reduced, most notably diones and chinones such
      as isatin or campherchinone. It was demonstrated that the enzymes often discussed
      for the reduction of beta-ketoesters with yeast e.g. L-3-hydroxyacyl CoA
      dehydrogenase (EC 1.1.1.35), the beta-ketoreductase of the fatty acid synthase
      complex and also the 3-hydroxy-3-methyl glutaryl-CoA dehydrogenase (EC 1.1.1.34)
      are separated during the purification steps from the oxidoreductase acting on N
      Boc-4S-amino-3-oxo-5-phenylpentanoic acid methylester. The physiological role of
      the new enzyme is still unknown.

PMID- 1369151
TI  - Process development for the recovery and purification of recombinant protein G.
AB  - The domains of protein G from streptococcus which bind immunoglobulin G have been
      cloned and expressed in Escherichia coli (Fahnestock et al., 1986). Because
      protein G binds to several animal immunoglobulin G's, it has many immunochemical
      applications. This report describes process development for large-scale
      production of this recombinant protein G (also known as GammaBind G). In 200 l
      cultures of E. coli, this protein G variant was released from the cell into the
      culture medium by heating at 80 degrees C for 10 min. The concentration was
      monitored by either a competitive enzyme-linked immunoassay or a liquid
      chromatographic assay. Cross-flow microfiltration with 0.22 micron membrane was
      used to remove the cells. The protein G-rich permeate from the cross-flow
      microfilter was purified by affinity chromatography using a 5 l column of IgG
      Sepharose 6 Fast Flow, which yielded 16-18 g of protein G per column cycle. The
      pools of purified protein G were concentrated and desalted using ultrafiltration.
      The salt-free protein G was then lyophilized as bulk product. The overall
      recovery through the entire process was 50-64%. The analysis of the final product
      included sodium dodecyl sulfate polyacrylamide gel electrophoresis, UV-visible
      spectrum, high performance gel filtration, endotoxin level and binding efficiency
      to human IgG Sepharose.

PMID- 1369152
TI  - Influence of constant and oscillating dissolved oxygen concentrations on keto
      acid production by Gluconobacter oxydans subsps. melanogenum.
AB  - Gluconobacter species are known to oxidise glucose via a direct oxidation pathway
      which is distinct from the pentose phosphate pathway. In the present
      communication results of an investigation on the influence of different dissolved
      oxygen concentrations (DO) on the production of 2,5-diketogluconic acid in batch
      and chemostat cultures are given. DO of 30% relative to air at 1 bar was found as
      a threshold level for optimum productivity. The positive influence of continuous
      availability of dissolved oxygen on the process of rapid glucose oxidation was
      unambiguously shown as the result of induction of membrane bound dehydrogenases
      involved in direct glucose oxidation. Furthermore data of scale-down experiments
      in which the organism was cultivated under oscillations of dissolved oxygen, are
      given. The influences of such oscillations of DO in the region of the established
      threshold (30% saturation) were found to result in a prolonged lag phase for
      growth and product formation. The data obtained in this study revealed critical
      residence times at low DO that could be employed as a criterion for scale up of
      this aerobic process.

PMID- 1369153
TI  - Improving the production of E. coli beta-lactamase in Bacillus subtilis: the
      effect of glucose, pH and temperature on the production level.
AB  - Bacillus subtilis has been considered a promising host for the production of
      foreign proteins. However, proteases released by the host organism can often
      cause rapid breakdown of secreted heterologous proteins. Here we report that the
      addition of 6% glucose and 100 mM potassium phosphate to the growth medium
      significantly reduces the degradation of E. coli TEM beta-lactamase secreted from
      B. subtilis, when applying an expression system based on B. amyloliquefaciens
      alpha-amylase. The yield of beta-lactamase was increased 10-20-fold when compared
      to the yield in Luria medium. The promoter of B. amyloliquefaciens alpha-amylase
      gene is repressed by glucose. However, here we show that the repression does not
      take place in a multicopy plasmid, thus enabling our approach to efficiently
      reduce the protease action by catabolite repression. We have also studied the
      role of pH and temperature on the beta-lactamase production in laboratory scale
      bioreactors. Low temperature and low pH are both favorable for a high level beta
      lactamase production by the high copy plasmid construction.

PMID- 1369154
TI  - 12 beta-Hydroxylation of digitoxin by suspension-cultured Digitalis lanata cells:
      production of digoxin in 20-litre and 300-litre air-lift bioreactors.
AB  - A biotransformation process for the production of digoxin was developed using
      Digitalis lanata cell suspension cultures. Digitoxin was used as the substrate
      for biotransformation. Digoxin production was carried out in a variety of
      vessels, including 1-l exsiccators, 20-l glass reactors and a 300-l air-lift
      bioreactor. A culture volume of 200 l was established after 28 d and the cells
      were then cultured semi-continuously in a 300-l bioreactor employing the draw
      fill cultivation method. Maximal digoxin production was achieved in an 8% glucose
      medium with a production optimum after 40-60 h of incubation in the presence of
      0.65-0.8 mmol digitoxin per l. Levels of 0.52, 0.53 and 0.60 mmol digoxin per l
      suspension were achieved in 1-l, 20-l and 300-l vessels, respectively. About 80%
      of the digoxin produced was found in the bathing medium.

PMID- 1369155
TI  - Expression in E. coli and purification of intracellular proteins by fusion to
      cyclomaltodextrin glucanotransferase.
AB  - A plasmid expression vector was constructed to direct the synthesis of foreign
      proteins in Escherichia coli as fusions with cyclomaltodextrin glucanotransferase
      (CGT) with cytoplasmic location (delta ssCGT). The ability of CGT to bind to
      covalently immobilized cyclodextrins was utilized in purifying fused target
      proteins. A large proportion of the cytoplasmically synthesized delta ssCGT
      formed inclusion bodies which adopted the active conformation at considerably
      high refolding concentration (67 microM delta ssCGT solution). By lowering the
      cultivation temperature the proportion of the soluble delta ssCGT was slightly
      increased. Intracellularly expressed delta ssCGT provides a potential affinity
      handle which forms easily refoldable inclusion bodies increasing the yield and
      stability, and possibly allows the expression of lethal target proteins.
      Interestingly, the interaction between one model fusion protein delta ssCGT-CAT
      (CAT, chloramphenicol acetyltransferase) and the E. coli heat shock protein GroEL
      was observed.

PMID- 1369157
TI  - Intergeneric protoplast fusion between Gluconobacter oxydans and Corynebacterium
      species.
AB  - Intergeneric protoplast fusion between 2,5-diketo-gluconic acid producing
      Gluconobacter oxydans (ATCC 9937) and a mutant strain of Corynebacterium species
      (ATCC 31090), capable of reducing 2,5-diketo-gluconic acid to 2-keto-L-gulonic
      acid, a penultimate step in vitamin C production) resulted in viable
      recombinants. Some of the fusion products exhibited the capacity to convert D
      glucose to 2-keto-L-gulonic acid, but the conversion rate is low.

PMID- 1369156
TI  - Gene expression following transfection of fish cells.
AB  - Various genes containing different transcriptional regulatory elements (TRE) and
      the bacterial marker gene coding for chloramphenicol acetyl transferase were
      transfected into several fish cell lines to evaluate the efficiency of expression
      in comparison with mammalian cells. The CMV and RSV TRE were the most efficient
      non-inducible promoters in directing reporter gene expression. RSV and CMV
      appeared of similar potency in a stable fish cell line. The human HSP-70 promoter
      showed high potency in a carp and in a trout cell line after thermal induction.
      This promoter also induced the synthesis of human growth hormone directed by the
      corresponding cDNA, but not by the gene. RSV TRE was also able to drive the
      synthesis of bovine growth hormone when attached directly to the cDNA but not to
      the gene. These data suggest that non-fish gene TRE can be used to express
      foreign genes in fish cells or transgenic fish; however, in most cases they are
      relatively inefficient. The data also suggest that the translation and secretion
      machinery of fish cells can express efficiently foreign genes but that mammalian
      introns might be not processed properly in some cases.

PMID- 1369158
TI  - Production of antimicrobials by Bacillus subtilis MIR 15.
AB  - We report the isolation and characterization of a strain of Bacillus, designed
      MIR 15, which appears to produce and excrete antimicrobials active against Gram
      negative bacteria, but not against fungi. B. subtilis MIR 15 varied its
      antimicrobial profiles and production with the cultivation temperature.

PMID- 1369159
TI  - Influence of the temperature on the shear stress sensitivity of adherent BHK 21
      cells.
AB  - The influence of temperature on the shear sensitivity of anchorage-dependent baby
      hamster kidney (BHK) cells was investigated. The temperature effect in general
      was compared for stressed and unstressed cells. Both the growth rate as well as
      the shear sensitivity are temperature-dependent. Decreasing the temperature
      lowered the growth rate and increased the ability of the BHK cells to withstand
      shear stress.

PMID- 1369160
TI  - Expression of Streptomyces genes encoding extracellular enzymes in Brevibacterium
      lactofermentum: secretion proceeds by removal of the same leader peptide as in
      Streptomyces lividans.
AB  - The alpha-amylase gene (amy) from Streptomyces griseus IMRU 3570 and the beta
      galactosidase gene (lac) from S. lividans were subcloned into Brevibacterium
      lactofermentum or B. lactofermentum/Escherichia coli shuttle vectors. The amy
      gene was not expressed in B. lactofermentum from its own promoter but was
      efficiently expressed when the promoter of the kanamycin resistance gene (kan)
      was inserted upstream of the promoterless amylase gene. The lac gene from S.
      lividans was subcloned without its native promoter and was expressed when placed
      downstream of pBL1 promoters P2 or P3. The alpha-amylase was secreted
      extracellularly by removal of the same 28-amino acid leader peptide as in S.
      lividans. The amy and lac genes provide useful markers for selection of
      transformants and will facilitate the study of protein secretion in B.
      lactofermentum.

PMID- 1369161
TI  - Cloning, sequence analysis and yeast expression of the egl1 gene from Trichoderma
      longibrachiatum.
AB  - A gene (egl1) encoding an endoglucanase (EGL1) from Trichoderma longibrachiatum
      has been cloned and sequenced. This gene, homologous to the T. reesei egl1 gene,
      differs from it in the length of the introns (particularly the first one) and
      encoded protein. A cDNA fragment obtained by the rapid amplification of cDNA ends
      method, which takes advantage of the polymerase chain reaction, has been
      expressed in yeast under control of the cyc-gal inducible promoter and yeast
      clones able to secrete active enzyme have been obtained.

PMID- 1369162
TI  - Differentiation of myoblasts and CNS cells grown either separately or as co
      cultures on microcarriers.
AB  - Dispersed neuronal and muscular elements from fetal or neonatal origin, can
      organize and mature in culture when grown on positively charged cylindrical
      microcarriers (MCS), to a stage which simulate in vivo maturation. Cells arrange
      themselves on the MCS to form aggregates which remain floating in the nutrient
      medium. In such a tridimensional organization, the neuronal tissue is capable of
      regenerating a network of nerve fibers which establish synapse interconnections
      and undergo myelination. Oligodendrocytes organize on MCS in a tridimensional
      pattern and produce extensive myelin-like membranes. Myoblasts in MC-cultures
      fuse into polynucleated myotubes which become striated and contract
      spontaneously. Creatine kinase and acetylcholine receptor (AChR) are formed
      during myogenesis in similar quantities in MC-cultures and in monolayers. When
      both neuronal and muscle tissues are prepared from the same fetus (autologous
      nerve-muscle co-cultures) and are cultured on MCS, they interconnect to form
      neuro-muscular junctions. Cells from both tissues, exhibit better
      differentiation, for longer periods in MC-cultures than they do in monolayers.
      The floating functional entities are easy to sample and can be harvested for
      ultrastructural, immunocytochemical and biochemical analysis. In addition, MC
      cultures can be used as a good tool for the study of acute and chronic exposures
      to toxicological agents, as well as for implantation into demyelinated, injured
      or dystrophic tissues. In this case the MCS in the implanted entities will serve
      as identifiable markers.

PMID- 1369163
TI  - An engineering analysis of rotating sieves for hybridoma cell retention in
      stirred tank bioreactors.
AB  - The use of internal rotating sieves for perfused hybridoma culture offers unique
      advantages but has been up to now largely empirical. Calculations have been
      performed on a 15 l spinfilter stirred tank in order to have an idea of
      hydrodynamic conditions inside and outside the rotating sieve. The large
      peripheral velocity value, resulting from sieve rotation (compared to axial and
      radial velocities) is expected to affect strongly sieve surface colonization by
      cells; this is confirmed by lab scale experiments, showing that cell colonization
      is prevented providing sieve rotation exceeds a defined value (around 0.6 m.s.1
      tip speed); the fluid removal force calculated under these conditions appears to
      be in the range of 10 pN, similar to the adhesion force already reported for
      mammalian cells attached to inorganic substrata.

PMID- 1369165
TI  - Physiology of myeloma cells grown in glucose-limited chemostat cultures.
AB  - A recombinant myeloma NS1-derived clone was grown in chemostat cultures in
      Dulbecco's MEM/Ham's F12 (1:1) medium containing various concentrations of
      glucose, at a dilution rate of 0.028 h-1. Serum-supplemented cultures were
      virtually glucose-limited at a large range of glucose feed concentrations (0.7-5
      mM). True glucose-limited cultures, however, were only established at low glucose
      supply levels to 1.3 mM at a maximum. In cultures obtained at higher glucose
      concentrations methionine was shown to be the growth-limiting compound. The
      pattern derived for serum-free chemostat cultures was similar, except that growth
      yields on glucose were much lower. Glucose was shown to be the growth-limiting
      substrate in cultures fed with media containing less than 4.5 mM glucose. Upon
      supplying glucose at higher concentrations such cultures presumably run into
      methionine and/or tryptophan limitation.

PMID- 1369164
TI  - Fragmented DNA and apoptotic bodies document the programmed way of cell death in
      hybridoma cultures.
AB  - Markers of apoptosis were followed in batch hybridoma cultures carried out in
      protein-free medium. Samples were collected on day 0, representing early
      exponential phase (viability 91%), and on day 8, corresponding to late stationary
      phase (viability 8%). The apoptotic index reflecting the relative number of
      bodies insoluble in 6 M guanidinium hydrochloride in the culture of day 8 (30%)
      exceeded markedly the index in the culture of day 0 (2.5%). A gel chromatography
      on Sepharose 2B was developed for quantitative evaluation of fragmented cellular
      DNA. This analysis, including a correction for nonspecific fragmentation, showed
      that on day 8 more than 30% of cellular DNA was fragmented, whereas on day 0 it
      was less than 5%. Control necrotic cells prepared by rapid killing in 1% sodium
      azide displayed a low apoptotic index (2.4%) and low DNA fragmentation.
      Electrophoretic patterns in agarose gel showed a typical "ladder" of fragments in
      the DNA sample of day 8. The demonstration of fragmented cellular DNA and of the
      high incidence of apoptotic bodies at late stationary phase adds substantial
      weight to the view that in hybridoma cultures apoptosis represents the prevalent
      mode of cell death.

PMID- 1369166
TI  - Enhancing monoclonal antibodies and hybridoma cell lines.
AB  - We are interested in determining the range of variants present in a cell
      population that can actually be isolated. We have used subcloning and sublining
      to search for variants with increased antibody stability, increased cell line
      stability to freezing and defrosting, increased cell population viability,
      increased antibody production and the ability to grow in simpler media. This
      paper presents the case histories of several different hybridoma cell lines which
      required some property changed before they became production ready clones. We
      found that switching the class of an antibody from IgG3 to IgG1 did increase its
      stability, decrease its tendency to aggregate and allowed it to be used in a
      commercial diagnostic kit. We could isolate subclones that produced twice the
      level of antibody with a frequency of 1-3%. It was straight forward to isolate
      clones that were stable to freezing and defrosting or grew in a simpler media. We
      were not successful in increasing the maximum viability of a cell line. In
      conclusion, we have found that any population of hybridoma cells has natural
      variants with significantly enhanced properties that can be isolated.

PMID- 1369167
TI  - Recombinant protein production in insect cell cultures infected with a
      temperature-sensitive baculovirus.
AB  - Spodoptera frugiperda (IPLB-SF-21) insect cells were grown in shake-flasks and
      infected with a temperature-sensitive baculovirus to express the gene of
      chloramphenicol acetyl transferase (CAT) in serum-free medium (SF-900) and two
      serum-supplemented media (IPL-41 and Grace's). In temperature-shift experiments
      (cell growth at 33 degrees C followed by virus replication at 27 degrees C 3-4
      days later), virus and CAT production were much poorer in the serum-free medium
      than in serum-supplemented media, though cell growth was virtually the same in
      the different media tested. In all the three media, highest virus and CAT titers
      were obtained at the lowest MOI (multiplicity of infection 0.02). This result is
      contrary to that obtained in constant-temperature culture (27 degrees C for both
      cell growth and virus replication). Virus and CAT production was greatly improved
      when the entire culture was run at constant temperature. It appeared that
      infected cells were severely damaged at 33 degrees C (6 degrees C above the
      optimal 27 degrees C), resulting in little or no virus and protein production. As
      a result of these temperature-shift experiments, a larger-scale (14 1 air-lift
      bioreactor) serum-free culture of Sf-9 insect cells was conducted at constant
      temperature (27 degrees C) to produce recombinant protein (beta-galactosidase). A
      cell density as high as 1 x 10(7) cells.ml-1, and a beta-gal concentration of up
      to 104,000 unit.ml-1 were achieved.

PMID- 1369168
TI  - Modelling the growth and protein production by insect cells following infection
      by a recombinant baculovirus in suspension culture.
AB  - A mathematical model has been developed to describe the growth and infection of
      insect cells by recombinant baculoviruses. The model parameters were determined
      from a series of independent experiments involving batch suspension culture. The
      profiles generated by the model for cell growth, virus production and protein
      production agree with those observed in experiments. Presently, the model
      simulates only systems where cells are not growth-limited. The model is useful in
      aiding the design and optimization of large-scale systems for production of
      biological insecticides as well as recombinant proteins and in delineating those
      areas which are limiting the process and require further, more fundamental,
      investigation.

PMID- 1369169
TI  - Expression of plasminogen activator and plasminogen activator inhibitor mRNA in
      human fibroblasts grown on different substrates.
AB  - mRNA levels for urokinase type plasminogen activator (uPA), tissue type
      plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and
      plasminogen activator inhibitor-2 (PAI-2) were examined in human diploid
      (neonatal foreskin) fibroblasts grown in 200-ml microcarrier suspension culture.
      Four different substrates were used. These included gelatin-coated polystyrene
      plastic, DEAE-dextran, glass-coated polystyrene plastic and uncoated polystyrene
      plastic. Our previous studies have shown that culture fluids from diploid
      fibroblasts grown on DEAE-dextran contained higher levels of plasminogen
      dependent fibrinolytic activity than culture fluids from the same cells grown on
      other substrates. The increased plasminogen activator activity was due largely to
      elevated amounts of tPA (In Vitro Cell. Develop. Biol. 22: 575-582, 1986). The
      present study shows that there is a corresponding elevation of tPA mRNA in
      diploid fibroblasts cultured on DEAE-dextran relative to the other substrates.
      There does not appear to be any difference in uPA mRNA or in mRNA for PAI-1 or
      PAI-2 produced by the same cells on the four substrates. These data suggest that
      the influence of the substrate on plasminogen activator production is mediated at
      the genetic level.

PMID- 1369170
TI  - The organotypic culture of human skin keratinocytes and fibroblasts to achieve
      form and function.
AB  - We describe an organotypic model of human skin comprised of a stratified layer of
      human epidermal keratinocytes and dermal fibroblasts within a contracted collagen
      lattice. Feasible and reproducible production of the skin construct has required
      the use of traditional as well as specialized culture techniques. The
      configuration of the construct has been engineered to maintain polarity and
      permit extended culture at the air-liquid interface. Morphological, biochemical
      and kinetic parameters were assessed and functional assays were performed to
      determine the degree of similarity to human skin. Light and ultrastructural
      morphology of the epidermis closely resembled human skin. The immunocytochemical
      localization of a number of differentiation markers and extracellular matrix
      proteins was also similar to human skin. Kinetic data showed a transition of the
      epidermal layer to a more in vivo-like growth rate during the development of the
      construct at the air-liquid interface. The barrier properties of the construct
      also increased with time reaching a permeability to water of less than 2%-h after
      approximately 2 weeks at the air-liquid interface which is still on average 30
      fold more water-permeable than normal human skin. The construct is currently used
      for in vitro research and testing and is also being tested in clinical
      applications.

PMID- 1369171
TI  - Experimental approaches to guarantee minimal risk of potential virus in purified
      monoclonal antibodies.
AB  - Regarding biological products, increasing awareness of potential side effects
      have placed great importance not only at protein purity regarding other proteins
      but on the removal of biologicals such as DNA and especially virus the importance
      of which may not be known. Monoclonal antibodies (Mab) have come to be an
      important class of molecules obtained from hybridoma cells, i.e., nonrecombinant
      cells in culture. It has been noted during the last years, that with rare
      exceptions hybridoma cell lines contain retrovirus like particles. The infectious
      nature of the EM-visible particles has been tested for, however, in most cases
      not been substantiated. In order to bring these valuable biological reagents,
      Mab's, to good use in man for imaging or therapy, the remaining concern about a
      potential retroviral infection has to be reduced to an acceptable minimum. We
      describe experimental approaches for the validation of chromatographic and
      ultrafiltration steps used in the production of monoclonal antibodies to remove
      and inactivate murine retrovirus. Present day biotechnological manufacturing
      processes have been devised incorporating a number of strategic preventive
      measures that have found wide spread acceptance. They permit to answer the
      question: how can a potentially harmful infection by an unknown virus be
      excluded. Knowledge of the efficacy of purification steps to clear infectious
      model virus is fundamental to devise biotechnological manufacturing processes
      yielding a purified antibody for use in man.

PMID- 1369172
TI  - Regulatory considerations when developing biological products. Report of the
      Center for Biologics Evaluation and Research.
AB  - The Center for Biologics Evaluation and Research, whose regulatory authority
      includes monoclonal antibodies, cytokines, vaccines, toxins and somatic cellular
      therapies, communicates to sponsors issues for consideration in the development
      of biological products through the publication of "Points to Consider" and
      "Guideline" documents. This paper summarizes the available "Points to Consider"
      and "Guideline" documents and outlines recommendations from these documents for
      characterizing the cells used to produce biological products.

PMID- 1369173
TI  - Avoiding rapid growth at high cell densities: a potentially important
      optimisation criterion for hybridoma cultures.
AB  - Inhibition caused by rapid changes in the environment has earlier been observed
      in hybridoma cultures following deliberate step-changes in the culture
      environment. This paper presents evidence of similar effects occurring during the
      normal span of continuous cultures fed enriched medium at low dilution rates
      (0.002-0.005 1/h). The effect of this observation on optimisation is discussed.
      In continuous culture at a dilution rate of 0.013 1/h, a viable cell density of 4
      x 10(9) cells/l was achieved by gradually increasing the nutrient concentration
      in the feed medium. The MAb titre was 200 mg/l representing a 6-fold increase
      compared to batch culture and a 2-fold increase compared to continuous culture
      using standard medium.

PMID- 1369174
TI  - DNA fingerprinting--a valuable new technique for the characterisation of cell
      lines.
AB  - DNA fingerprinting is an important new development for the authentication of cell
      lines. Multilocus methods such as those developed by Alec Jeffreys provide
      information on a wide range of genetic loci throughout the human genome and thus
      give a useful genetic "snap-shot" of a cell culture. Our work has shown that
      Jeffreys multilocus fingerprinting method can be applied to cell lines from a
      wide range of animals including reptiles, birds, fish and diverse mammals. It can
      also differentiate very closely related cell lines including those from the same
      mouse strain. Routine fingerprint analysis has enabled an unprecedented level of
      confidence in the consistency of cell stocks. Our results demonstrate that this
      straightforward method represents a powerful and readily interpreted system for
      cell authentication and exclusion of cross-contamination.

PMID- 1369175
TI  - Monitoring hybridoma metabolism in continuous suspension culture at the
      intracellular level. I. Steady-state responses to different glutamine feed
      concentrations.
AB  - A model mouse hybridoma cell line was grown in continuous culture experiments in
      a serum-free low-protein lipid-free medium. The steady-state responses of cell
      numbers, extra- and intracellular metabolite concentrations, substrate and (by)
      product consumption/production rates, and yield coefficients were investigated as
      a function of step changes in the glutamine concentration of the feed medium. In
      addition to the commonly performed analysis of metabolites in culture
      supernatants, we prepared perchloric acid extracts of cells and determined the
      amount and the composition of intracellular amino acids and organic acids.
      Significant differences were found with respect to intracellular metabolite pools
      for cells growing at nearly identical specific growth rates. To our knowledge
      this is the first time that data on the intracellular concentrations (pools) of
      amino acids and Krebs cycle intermediates are reported in the literature that
      were obtained under carefully defined culture conditions such as those attained
      in continuous culture experiments.

PMID- 1369176
TI  - Effect of amplification of dhfr and lac Z genes on growth and beta-galactosidase
      expression in suspension cultures of recombinant CHO cells.
AB  - Studies were conducted to characterize the effect of gene amplification and
      foreign gene expression on recombinant CHO cell growth. Chinese hamster ovary
      (CHO) cells were transfected with an expression vector containing the gene for
      dihydrofolate reductase (dhfr) and the gene for human beta-interferon (beta-IFN)
      or the lac Z gene which codes for beta-galactosidase (beta-gal). The recombinant
      genes in these CHO cells were amplified stepwise by growth in 0, 10(-7), and 10(
      6) M methotrexate (MTX), and the beta-gal expressing cells were adapted to
      suspension culture. Flow cytometric methods (FCM) were used to measure the
      distribution of amplified dhfr gene content and foreign beta-gal gene expression
      in the cell populations. A biochemical assay for beta-gal was also used. Beta-gal
      expression was found to increase with increasing gene amplification. The growth
      rate of recombinant CHO cells at 10(-7) M MTX was found to be 20% lower than that
      of recombinant CHO cells in MTX-free medium, and the cell growth rate at 10(-6) M
      MTX was 20% lower than that of recombinant CHO cells at 10(-7) M MTX. There was
      no effect of 10(-5) M MTX on the growth of CHO-DG44 (dhfr-) cells. The reduction
      of growth rate in recombinant CHO cells is therefore thought to be mainly due to
      the effect of dhfr and foreign gene amplification and increased beta
      galactosidase expression.

PMID- 1369177
TI  - Flow cytometry and two-dimensional electrophoresis (2-DE) for system evaluation
      of long term continuous perfused animal cell cultures in macroporous beads.
AB  - Immobilization of r-CHO cells at high density using macroporous polyethylene
      carriers in a modular fluidized bed reactor is demonstrated. Specific growth
      rates of the cells are measured by incorporation of BrdU. At a cell density of
      about 10(8) cells/ml a stable growth rate of 0.004 h-1 was established. Total
      release of proteins into the culture supernatant during protein-free perfusion
      was analyzed by 2-DE in various phases of the long-term culture showing very
      similar patterns indicating a constant pattern of gene expression.

PMID- 1369178
TI  - Design and performance of a trickle-bed bioreactor with immobilized hybridoma
      cells.
AB  - A trickle-bed system employing inert matrices of vermiculite or polyurethane foam
      packed in the downcomer section of a split-flow air-lift reactor has been
      developed for hybridoma culture to enhance antibody productivity. This quiescent
      condition favoured occlusion and allowed the cells to achieve densities twelve
      fold greater (12.8 x 10(6) cells/ml reactor for polyurethane foam) than in free
      cell suspension. The reactor was operated in a cyclic batch mode whereby defined
      volumes of medium were periodically withdrawn and replaced with equal volumes of
      fresh medium. The pH of the medium was used as the indicator of the feeding
      schedule. Glucose, lactate and ammonia concentrations reached a stationary value
      after 5 days. With vermiculite packing, a monoclonal antibody (MAb) concentration
      of 2.4 mg/l was achieved after 12 days. The MAb concentration declined then
      increased to a value of 1.8 mg/l. In the polyurethane foam average monoclonal
      antibody (MAb) concentrations reached a stationary value of 1.1 mg/l in the first
      20 days and increased to a new stationary state value of 2.1 mg/l for the
      remainder of the production. MAb productivity in the trickle-bed reactor was 0.3
      mg/l.d (polyurethane foam) and 0.18 mg/l.d (vermiculite) in comparison to 0.12
      mg/l.d for free cell suspension. This trickle-bed system seems to be an
      attractive way of increasing MAb productivity in culture.

PMID- 1369179
TI  - Maximisation of perfusion systems and process comparison with batch-type
      cultures. Maximisation of perfusion cultures.
AB  - A comparison of cell yields and monoclonal antibody productivity from the same
      hybridoma has been made in a wide range of cell bioreactors including both batch
      and continuous perfusion cultures. The most productive systems were based on
      porous microcarriers in fixed and fluidised beds which can be operated with a
      high degree of efficiency and reliability from the physico-chemical engineering
      point of view. Further improvements should be possible by improving the
      physiological environment in dense cell cultures, as indicated by the preliminary
      studies that are described. These include experimental data showing the
      relationship between monoclonal antibody production rates with glucose,
      glutamine, ammonia, and oxygen levels in microporous beads. The results strongly
      indicate that perfusion processes that are scaleable in both volume and cell
      density can significantly reduce production costs. Manufacturers of biologicals
      from animal cells now have a choice between the proven batch-type processes and
      reliable perfusion systems based on microporous beads.

PMID- 1369180
TI  - Modified CelliGen-packed bed bioreactors for hybridoma cell cultures.
AB  - This study describes two packed bed bioreactor configurations which were used to
      culture a mouse-mouse hybridoma cell line (ATCC HB-57) which produces an IgG1
      monoclonal antibody. The first configuration consists of a packed column which is
      continuously perfused by recirculating oxygenated media through the column. In
      the second configuration, the packed bed is contained within a stationary basket
      which is suspended in the vessel of a CelliGen bioreactor. In this configuration,
      recirculation of the oxygenated media is provided by the CelliGen Cell Lift
      impeller. Both configurations are packed with disk carriers made from a non-woven
      polyester fabric. During the steady-state phase of continuous operation, a cell
      density of 10(8) cells per cm3 of bed volume was obtained in both bioreactor
      configurations. The high levels of productivity (0.5 gram MAb per 1 of packed bed
      per day) obtained in these systems demonstrates that the culture conditions
      achieved in these packed bed bioreactors are excellent for the continuous
      propagation of hybridomas using media which contains low levels (1%) of serum as
      well as serum-free media. These packed bed bioreactors allow good control of pH,
      dissolved oxygen and temperature. The media flows evenly over the cells and
      produces very low shear forces. These systems are easy to set up and operate for
      prolonged periods of time. The potential for scale-up using Fibra-cel carriers is
      enhanced due to the low pressure drop and low mass transfer resistance, which
      creates high void fraction approaching 90% in the packed bed.

PMID- 1369181
TI  - The membrane dialysis bioreactor with integrated radial-flow fixed bed--a new
      approach for continuous cultivation of animal cells.
AB  - A hybridoma cell was cultivated continuously in a membrane dialysis bioreactor
      with an integrated radial-flow fixed bed consisting of porous Siran carriers over
      a period of 6 weeks. Antibodies accumulated to an average of 100 mg l-1, approx.
      10 times more than in fixed bed cultures without dialysis membrane. Serum costs
      could be reduced about 85% due to an appropriate feeding strategy. Siran carriers
      with 3-5 mm diameter showed an advantage compared to those with 1-2 mm diameter.
      For the 3-5 mm carrier the specific glucose uptake rate and the MAb production
      rate were constant, if the velocity was between 0.09 mm s-1 and 0.75 mm s-1. At
      higher velocities cells are washed out of the bed. Furthermore antibody
      consistency and cell stability were verified in long-term cultivations over a
      period of 96 days. From an estimation of the antibody concentration reachable
      with the reactor concept under optimal conditions a concentration 45 times higher
      compared to axial-flow fixed bed reactors and 11 times higher compared to stirred
      tank reactors can be expected.

PMID- 1369182
TI  - Optimal medium use for continuous high density perfusion processes.
AB  - For maintenance of high cell density in continuous perfusion processes not only
      feeding with substrates but also removal of inhibitors and toxic waste products
      are of special interest. High perfusion rates cause large volumes of product
      containing medium which have to be processed in product isolation. In order to
      minimize these volumes concentrated feed solutions of optimized medium are used.
      On the other hand, such media may cause high concentrations of toxic or
      inhibitory metabolites which can negatively influence cell growth and product
      formation. Especially, if the spent medium (or special parts of it) is used again
      after product isolation, the removal or even better the control of inhibitor
      production is of highest importance. We have developed a continuous fermentation
      concept and system (continuous medium cycle bioreactor, cMCB) in which both
      limitation and inhibition effects can be generated to identify special substances
      as limiting or inhibitory components. With the results from those experiments it
      was possible to lower the total perfusion rate during serum-free perfusion
      cultures of hybridoma cells and to obtain an optimal substrate utilization. The
      advantages for decreasing the production costs (for media, special supplements
      and product isolation) are obvious. The other aim of this study was to identify
      secreted metabolic waste products as inhibitor or toxic metabolite.

PMID- 1369183
TI  - Novel cell lines derived from transgenic mice expressing recombinant human
      proteins. Transgenic hepatoma-derived cell lines.
AB  - We have used transgenic mouse technology to establish immortalized hepatoma cell
      lines stably secreting heterologous proteins, such as human alpha 1-antitrypsin
      and human factor IX. Hepatocyte-specific regulatory DNA sequences were used to
      target both the expression of an onc gene and the gene coding for the human
      protein to the liver of transgenic mice which eventually developed hepatocellular
      carcinomas. Tumour cells were subsequently established as permanent cell lines,
      which maintained a differentiated phenotype under specific culture conditions,
      being capable of producing biologically active and correctly processed human
      alpha 1-antitrypsin and factor IX. Moreover, a preliminary analysis has shown
      that certain cell lines express elevated total cytochrome P450 activity. These
      cells could therefore represent a useful alternative to the use of animals or
      primary cultures in drug safety testing.

PMID- 1369184
TI  - Expression of human alpha 1 antitrypsin in transgenic sheep.
AB  - We have recently described the production of large amounts (< or = 65 grams per
      litre) of enzymatically active human alpha 1 antitrypsin in the milk of
      transgenic sheep (Wright et al., 1991). Here, we describe in more detail the
      expression of the human protein in the milk of these animals throughout the
      lactation period. Human alpha 1 antitrypsin is also found at much lower levels in
      the plasma of transgenic ewes before, during and after lactation. It is also
      detected in male plasma at very low levels. We have previously shown human alpha
      1 antitrypsin purified from transgenic sheep milk to be indistinguishable from
      commercially available human plasma derived alpha 1 antitrypsin in terms of gross
      sugar content and in vitro activity. Here we extend this comparison to more
      detailed analyses of glycosylation state, amino-terminal sequence, pI value, and
      molecular weight determination by mass spectrometry.

PMID- 1369185
TI  - Specific monoclonal antibody productivity and the cell cycle-comparisons of
      batch, continuous and perfusion cultures.
AB  - A selection of mouse hybridoma cell lines showed a variation of approximately two
      orders of magnitude in intracellular monoclonal antibody contents. The different
      levels directly influenced apparent specific monoclonal antibody productivity
      during the death phase but not during the growth phase of a batch culture. The
      pattern of changes in specific productivity during culture remained basically
      similar even though at different levels for all cell lines tested. Arresting the
      cells in the G1 phase using thymidine increased the specific productivity, cell
      volume and intracellular antibody content but at the same time led to decreased
      viability. In continuous culture DNA synthesis decreased with decreasing dilution
      rate though without an accompanying change in cell cycle and cell size
      distributions. The data shows both the decrease in viability and intracellular
      antibody content to be important factors which influence the negative association
      between specific antibody productivity and growth rate. In high cell density
      perfusion culture, when the cell cycle was prolonged by slow growth, viability
      was low and dead, but not lysed, cells were retained in the system, the specific
      antibody productivity was nearly two fold higher than that obtained in either
      batch or continuous cultures. The results imply that the prolongation of G1 phase
      and the increase in death rate of cells storing a large amount of antibody
      together cause an apparent increase in specific antibody productivity.

PMID- 1369186
TI  - The role of laminin in attachment, growth, and differentiation of cultured cells:
      a brief review.
AB  - Laminin, a major structural multidomain protein of basement membranes, has been
      shown to exert a variety of biological activities. Prominent among those are
      mediation of cell attachment as well as influences on cellular proliferation,
      differentiation and motility. Distinct domains of laminin have been identified
      which carry these activities. The active sites on laminin are recognized by
      cellular receptors, several of which belong to the integrin class of
      heterodimeric transmembrane proteins. These are in direct contact with
      intracellular proteins and mediate signals from the extracellular matrix to the
      cytoskeleton and possibly to other intracellular regulatory systems. The
      biological activities of laminin may be used to design optimal conditions for the
      expression of a differentiated phenotype of cells in culture.

PMID- 1369187
TI  - Comparison of culture methods and an immunofluorescence assay for the detection
      of Legionella pneumophila in domestic hot water devices.
AB  - The objective of this study was to compare an indirect immunofluorescence assay
      with culture methods for the identification of Legionella pneumophila serogroups
      1 to 6 in hot water samples taken from domestic environments. Hot water samples
      were obtained from the water heater, the shower heads, and the most frequently
      used faucet of 211 private houses. Concentrated water samples were inoculated on
      buffered charcoal yeast extract agar (BCYE) and on a semi-selective culture
      medium (GPV). Colonies with a morphology similar to that of Legionellaceae were
      subcultured on BCYE and on blood agar plates; those that grew on the former but
      not the latter were further characterized and identified by direct
      immunofluorescence techniques. The concentrated samples were also smeared on
      multiple-well microscope slides and tested by indirect immunofluorescence with
      monoclonal antibodies against L. pneumophila, serogroups 1 to 6. Of the houses
      studied, 30% were found to contain culturable L. pneumophila in at least one
      water sample, whereas 63% were positive by indirect immunofluorescence. The
      sensitivity of this assay compared with culture varied from 16.7-21.1%, and its
      specificity was between 76.7% and 88.3% depending on the sample source (water
      heater, shower heads, or faucet). In the 38 houses with at least one positive
      sample found by both immunofluorescence and culture, total or partial agreement
      between serogroups identified by both techniques was only 34%. The results
      obtained in this study strongly suggest that indirect immunofluorescence is not
      an adequate alternative for the identification of L. pneumophila in hot water
      systems.

PMID- 1369188
TI  - High-frequency electroporation and maintenance of pUC- and pBR-based cloning
      vectors in Pseudomonas stutzeri.
AB  - A number of Escherichia coli cloning vectors, based on ColE1-like replicons, were
      shown to be maintained in Pseudomonas stutzeri ATCC 17588. A restrictionless
      mutant of P. stutzeri was isolated, and this strain was used to develop an
      efficient electroporation system. With the E. coli cloning vector pHSG298,
      transformation frequencies of up to 2 x 10(7) transformants/micrograms DNA were
      achieved. This frequency is comparable to that obtained for CaCl2-mediated
      transformation of E. coli; thus, direct cloning of DNA into P. stutzeri is
      feasible. As will be discussed, this may prove useful for cloning DNA from high
      mol% G + C genera in cases in which E. coli is not a suitable heterologous
      cloning host.

PMID- 1369189
TI  - Characterization of Zymomonas mobilis alkaline phosphatase activity in
      Escherichia coli.
AB  - Zymomonas mobilis phoA gene encoding alkaline phosphatase was expressed in
      Escherichia coli CC118 carrying the recombinant plasmid pZAP1. The pH optimum for
      this enzyme was 9.0 and showed a peak activity at 42 degrees C. This enzyme
      required Zn2+ for its catalytic activity; however, Mg2+ or Ca2+ significantly
      affected the activity. This enzyme was found to be ethanolabile, and ethanol
      inhibition was reversed by addition of Zn2+. Kinetics of Z. mobilis alkaline
      phosphatase production in E. coli CC118 (pZAP1) showed that the enzyme activity
      was growth associated and localized in the cellular fraction, and the maximum
      activity was found in the stationary phase.

PMID- 1369190
TI  - Phase variations in Bifidobacterium animalis.
AB  - Strains isolated from rabbit, chicken, and rat feces and from sewage and
      fermented milk products, all identified as Bifidobacterium animalis, were found
      to show phase variations in colony appearance and in cellular morphology. The
      rate of transition in a switching system from opaque to transparent colonies and
      vice versa was determined. Differences in protein components and in penicillin
      binding proteins (PBPs) of the cells from different colony types are shown.

PMID- 1369191
TI  - Change of speciation of Cu(II) in growth medium due to uptake of ammonia by
      Pseudomonas testosteroni during growth.
AB  - Growth of Pseudomonas testosteroni in a medium containing 1 mM Cu(II) causes a
      color change from blue to green. The spectrum of the supernatant solution from
      the blue culture shows an absorption at 660 nm, identical to that of 1 mM
      [Cu(II)] in the medium. The green supernatant solution shows a UV absorption,
      which tails into the visible and so is responsible for the green color, and a d-d
      absorption at 720 nm. The absorption at 660 nm for the blue supernatant solution
      is probably due to [Cu(NH3)3(H2O)3]2+. Growth of the organism causes loss of
      ammonia and a speciation change to [CU(NH3)2(H2O)4]2+, with a shift in absorption
      maximum from 660 to 720 nm. These conclusions are based upon the spectra of known
      aquaammine complexes of Cu(II) and calculations of the speciation of Cu(II)
      before and after growth. Change in metal speciation owing to nutrient uptake by
      an organism does not appear to have been recognized previously.

PMID- 1369192
TI  - Anoxygenic degradation of aromatic substances by Rhodopseudomonas palustris.
AB  - Three strains of the phototrophic purple nonsulfur bacterium Rhodopseudomonas
      palustris were isolated from different environments and were evaluated for their
      aromatic degradative potential under phototrophic conditions. All three strains
      (PFR1, PNR4, and MRL1) utilized benzoate, 4-hydroxybenzoate, 4-aminobenzoate, 4
      aminophenol, cinnamate, ferulate, phloroglucinol, and 4-dimethylaminobenzaldehyde
      in the absence of exogenous CO2. 4-Aminobenzoate and 4-aminophenol served as a
      carbon and nitrogen source for all the three strains. Utilization of 4
      aminophenol was enhanced in the presence of 4-hydroxybenzoate. Salicylate was
      utilized by PFR1 and MRL1 strains, and phenol was utilized by the MRL1 strain
      only in the presence of exogenous CO2.

PMID- 1369193
TI  - Sensitization of oral bacteria to killing by low-power laser radiation.
AB  - Twenty-seven compounds were screened for their ability to sensitize Streptococcus
      sanguis to killing by light from a 7.3-mW Helium/Neon (HeNe) laser. Bacteria were
      mixed with various concentrations of the test compounds, spread over the surfaces
      of agar plates, and then exposed to light from the HeNe laser for various time
      periods. The plates were then incubated and examined for zones of inhibition.
      Those compounds found to be effective photosensitizers were then tested against
      Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Fusobacterium
      nucleatum. Toluidine blue O, azure B chloride, and methylene blue at
      concentrations of 0.005% (wt/vol) were effective photosensitizers of all four
      species, enabling killing of bacteria following exposure to laser light for only
      30 s.

PMID- 1369194
TI  - Correlation between the virulence of Francisella tularensis in experimental mice
      and its acriflavine reaction.
AB  - Correlation between the virulence of Francisella tularensis in experimental mice
      and its acriflavine reaction was studied. The cultures derived from all four
      strains (Ebina, CMB2, Schu, and N9) that had long been subcultured on agar media
      yielded two types of colonies, i.e., acriflavine reaction-positive (acf+) and
      acriflavine reaction-negative (acf-) colonies. All acf+ colonies, regardless of
      their parent strains, were shown to be low virulent in mice. Acf- colonies were
      shown to be either high (Ebina, CMB2) or low (Schu, N9) virulent. The low
      virulent acf- colonies gained virulence during several passages in mice, whereas
      the acf+ colonies remained low virulent even after the animal passages.

PMID- 1369195
TI  - A 28-kilodalton fibronectin-binding protein of group A streptococci.
AB  - Lipoteichoic acid (LTA) has been implicated as a major adhesin of group A
      streptococci that interacts with fibronectin (Fn). It has been suggested that
      protein adhesins may also be involved in the binding of Fn to streptococci. We
      searched for such a protein by transblotting membrane preparations from M types
      5, 19, and 24 group A streptococci to nitrocellulose and reacting the blot with
      125I-Fn. The Fn reacted with a 28-kDa polypeptide from all three serotypes of
      streptococci. Using affinity-purified antibodies to the 28-kDa protein in
      immunoblots of membrane preparations from various streptococci, we demonstrated
      that the 28-kDa protein is present in all 17 strains tested. Affinity-purified
      antibodies to the 28-kDa protein also reacted in varying degrees with intact
      streptococci, demonstrating that the antigen is exposed on the surface of intact
      organisms. Our results suggest that, in addition to LTA, group A streptococci
      contain a common Fn-binding moiety that is expressed as a major component of
      membrane preparations and that is accessible on the surface of streptococci for
      interactions with Fn.

PMID- 1369196
TI  - Role of nalidixic acid in isolation of Salmonella typhimurium strains capable of
      growth at 48 degrees C.
AB  - Salmonella typhimurium thermotolerant mutants dependent on the presence of
      nalidixic acid for growth at 48 degrees C were isolated and designated nalidixic
      acid-dependent, thermotolerant mutants, naldttl. Genetic mapping revealed that
      naldttl alleles map within the gyrA gene. When S. typhimurium strain Q was plated
      in the dark on nutrient agar containing nalidixic acid (20 micrograms/ml) as a
      photosensitizer and briefly exposed to white light or near VU light prior to
      incubation at 42 degrees C, nalidixic acid-resistant mutants arose in about 16 h
      at frequencies of 5 x 10(-8) for white light and 1 x 10(-6) for near UV light.
      About 10% of these nalidixic acid-resistant mutants derived from photodynamic
      mutagenesis exhibited the thermotolerant characteristic.

PMID- 1369197
TI  - Purification and characterization of an aminopeptidase from Streptococcus mitis
      ATCC 903.
AB  - An aminopeptidase isolated from the cytoplasmic fraction of a cell extract of
      Streptococcus mitis ATCC 903 was purified 330-fold by ion-exchange
      chromatography, gel filtration, and hydroxyapatite chromatography. The partially
      purified enzyme had a broad substrate specificity. Twelve aminoacyl-beta
      naphthylamide substrates were hydrolyzed and also several di-, tri-, tetra-, and
      pentapeptides and bradykinin. The enzyme hydrolyzed arginine-beta-naphthylamide
      at the highest rate. Optimal conditions for activity were at pH 7.0-7.2 and at 37
      40 degrees C. The molecular weight of the enzyme was estimated to be 93,000. The
      enzyme was activated by Co2+ ions. Hg2+ inhibited the activity completely. SDS,
      EDTA, urea, and pCMB also inhibited activity. Inhibition by EDTA could be
      completely reversed by dialysis and addition of Co2+ ions. Reducing agents,
      sodium fluoride, and PMSF had no effect on the activity of the enzyme. The
      isoelectric point of the enzyme was at pH 4.3. High substrate concentrations
      inhibited activity. Substrate inhibition increased in the presence of high
      concentrations of Co2+ ions.

PMID- 1369198
TI  - Molecular cloning and expression of Bacillus subtilis bglS gene in Saccharomyces
      cerevisiae.
AB  - A 2.7-kb EcoRI DNA fragment carrying a Bacillus subtilis endo-beta-1,3-1, 4
      glucanase gene (bglS) from the E. coli plasmid pFG1 was cloned into an
      Escherichia coli/yeast shuttle vector to construct a hybrid plasmid YCSH. The
      hybrid plasmid was used to transform Saccharomyces cerevisiae, and the bglS gene
      was expressed. Variation between levels of bglS gene expression in S. cerevisiae
      was about 2.3-fold, depending on the orientation of the 2.7-kb DNA fragment.
      Assay of substrate specificity and optimal pH of the enzyme demonstrated that the
      enzyme encoded by YCSH (bglS) was identical with that found in B. subtilis, but
      the expression level of bglS gene in S. cerevisiae (YCSH) was much lower than
      that in E. coli (YCSH).

PMID- 1369200
TI  - Cloning and expression in Escherichia coli of an alkaline phosphatase (phoA) gene
      from Zymomonas mobilis.
AB  - An alkaline phosphatase (phoA) gene from Zymomonas mobilis was isolated in
      Escherichia coli CC118 by use of the plasmid Bluescript KS+. The origin of the
      6.4-kb DNA fragment in pZAP1 from the chromosome of Z. mobilis was confirmed by
      Southern blotting and hybridization studies. The Z. mobilis phoA gene was
      localized at one end of the chromosomal insert on plasmid pZAP1. The Z. mobilis
      phoA gene was expressed from its own promoter in E. coli, and the enzyme was
      localized to the periplasmic space. Z. mobilis alkaline phosphatase activity in
      E. coli was repressed in high-phosphate media and derepressed under a phosphate
      limited growth condition. These results suggest that Z. mobilis alkaline
      phosphatase is subjected to normal regulation in E. coli.

PMID- 1369199
TI  - Sequence analysis of an aphid endosymbiont DNA fragment containing rpoB (beta
      subunit of RNA polymerase) and portions of rplL and rpoC.
AB  - The aphid Schizaphis graminum is dependent on an association with a prokaryotic
      endosymbiont (Buchnera aphidicola). The nucleotide (nt) sequence of a 5040 base
      pair (bp) DNA fragment of B. aphidicola, homologous to the rplL-rpoB-rpoC portion
      of the Escherichia coli beta operon, was determined. The DNA coded for the
      terminal 35 amino acids of RplL (large ribosomal subunit protein L7/L12), the
      complete RpoB (beta-subunit of RNA polymerase), and the first 209 amino acids of
      RpoC (beta'-subunit of RNA polymerase). The deduced sequences of B. aphidicola
      RplL, RpoB, and RpoC were 71, 84, and 91% identical, respectively, to the
      homologous proteins of E. coli. The sequences of two portions of the intergenic
      region between rplL and rpoB were nearly identical in both B. aphidicola and E.
      coli. One sequence constituted an inverted repeat that could be an RNase III
      messenger RNA processing site; the other sequence preceded RpoB. A compilation of
      the codon usage for RpoB, RpoC, and other B. aphidicola proteins indicated a
      major preference for A or T in the first and third positions, a result consistent
      with the low guanine plus cytosine (G + C) content of the DNA of this organism.

PMID- 1369201
TI  - Away from home: U.S. sites of European and Japanese biotech R&D.

PMID- 1369202
TI  - Cell disruption: breaking up is hard to do.

PMID- 1369203
TI  - Biotechnology in an uncommon market.

PMID- 1369204
TI  - Recombinant protein expression in high cell density fed-batch cultures of
      Escherichia coli.
AB  - Whereas cell concentrations of 5-10 grams dry cell weight per liter (gDCW/l) are
      typical of batch cultures, fed-batch techniques can be used to achieve
      concentrations greater than 50 gDCW/l. Feeding strategies for fed-batch cultures
      include feed-back control as well as pre-determined feeding profiles. The
      volumetric yield of recombinant products can be improved by controlling the
      specific growth rate and the substrate concentration. Furthermore, inhibitory by
      product formation can be minimized in fed-batch cultures. This review focuses on
      the use of fed-batch techniques to produce recombinant products in Escherichia
      coli. The modes of nutrient feeding that have been employed are discussed, and
      the factors important in attaining high cell concentrations as well as high
      specific yields of recombinant product are described.

PMID- 1369205
TI  - An algorithmically optimized combinatorial library screened by digital imaging
      spectroscopy.
AB  - Combinatorial cassettes based on a phylogenetic "target set" were used to
      simultaneously mutagenize seven amino acid residues on one face of a
      transmembrane alpha helix comprising a bacteriochlorophyll binding site in the
      light harvesting II antenna of Rhodobacter capsulatus. This pigmented protein
      provides a model system for developing complex mutagenesis schemes, because
      simple absorption spectroscopy can be used to assay protein expression,
      structure, and function. Colony screening by Digital Imaging Spectroscopy showed
      that 6% of the optimized library bound bacteriochlorophyll in two distinct
      spectroscopic classes. This is approximately 200 times the throughput (ca. 0.03%)
      of conventional combinatorial cassette mutagenesis using [NN(G/C)]. "Doping"
      algorithms evaluated in this model system are generally applicable and should
      enable simultaneous mutagenesis at more positions in a protein than currently
      possible, or alternatively, decrease the screening size of combinatorial
      libraries.

PMID- 1369206
TI  - Hyperthermostable variants of a highly thermostable alpha-amylase.
AB  - Genetic screening at temperatures between 70-80 degrees C far exceeds the range
      of growth of most bacteria, and is not applicable to isolate easily thermostable
      protein variants. We describe a temperature shift protocol and an in vivo
      screening method which allowed us to identify a hyperthermostable variant of the
      thermostable alpha-amylase from Bacillus licheniformis. Our strategy was to
      select, after hydroxylamine mutagenesis, an intragenic suppressor mutation which
      overcomes a mutation leading to a thermolabile enzyme. Sequence analysis of the
      mutated gene revealed only one change in the amino acid sequence, substituting a
      valine for alanine at position 209. This single amino acid replacement increased
      the half-life of the protein at 90 degrees C by a factor of two to three relative
      to the wild-type enzyme. When this substitution was combined with another
      stabilizing substitution (H133Y) we described previously, the stabilizing effects
      were additive. The half-life of the new protein was about 12 hours at 90 degrees
      C, corresponding to a nine to ten-fold increase over the wild-type enzyme and the
      industrial Bacillus licheniformis alpha-amylase Termamyl. These mutations are
      located in a predicted folding domain of the protein which appears crucial in
      determining thermal stability.

PMID- 1369207
TI  - Importance of dietary cholesterol for the maturation of mouse brain myelin.
AB  - The effect of nil (control), 1% (CH-1) and 5% (CH-5) dietary cholesterol on the
      myelination of mouse brain, and its deposition in the heart and liver were
      investigated during infancy. Swiss Webstar female mice were given formulated
      diets from early gestation, and their pups were weaned on the same diet as that
      of the individual mothers up to 60 days after birth. The test diets increased the
      liver weight and cholesterol content compared to the control even in suckling
      pups (20 days), but did not significantly influence the heart weight until 60
      days. The cholesterol content of the heart was not increased by the CH-1 diet
      throughout the feeding period, but it did increase the mole ratio of major myelin
      lipids and hastened its maturation. Myelin cholesterol was 10% higher in 20-day
      old suckling pups in the CH-5 group compared to the control. Data indicate that
      dietary cholesterol altered the brain myelination rate of weaning mice, and that
      the mother's dietary cholesterol influenced myelination of the suckling pups.

PMID- 1369209
TI  - Purification and characterization of immunoglobulin production stimulating factor
      II beta derived from Namalwa cells.
AB  - Two immunoglobulin production stimulating factors (IPSF) have been found in human
      Burkitt's lymphoma Namalwa cells. One IPSF named IPSF-II alpha was purified and
      identified as glyceraldehyde-3-phosphate dehydrogenase as previously reported. We
      report here purification, identification and characterization of IPSF-II beta.
      IPSF-II beta was purified by the serial use of ammonium sulfate fractionation,
      hydrophobic interaction column chromatography, anion-exchange column
      chromatography and gel filtration. The IPSF-II beta was estimated as a 46 KD
      monomeric polypeptide by gel filtration and SDS-PAGE. Partial amino acid sequence
      of the 46 KD protein was analyzed for 26 amino acid residues. The sequence very
      closely coincided with enolase (EC 4.2.1.11) derived from various origins and, it
      was completely homologous with that of human enolase alpha-chain. Rabbit muscle
      enolase stimulated IgM production of hybridoma lines, and IPSF-II beta had the
      enzymic activity. These results suggested that IPSF-II beta was alpha-enolase or
      its isozyme. IPSF activities of IPSF-II beta was stable in alkaline conditions
      whereas the enzymic activity was rapidly lost in alkaline conditions. Though IPSF
      II beta stimulated IgM production of both human-human and mouse-mouse hybridoma
      lines in serum-free condition, it partially suppressed IgE production of mouse
      mouse hybridoma lines.

PMID- 1369208
TI  - Construction of a toxic insulin molecule: selection and partial characterization
      of cells resistant to its killing effects.
AB  - We have constructed an insulin-diphtheria hormono-toxin which migrates as a
      single 29 kd band on 10% SDS polyacrylamide gel electrophoresis. This corresponds
      to a one to one molar ratio of the diphtheria A-chain (23 kDa) and insulin (6
      kDa) molecules. The diphtheria A-chain: insulin (DTaI) hormono-toxin demonstrates
      cytotoxicity in V-79 Chinese hamster cells exhibiting an LD50 of 1.1 x 10(-8) M,
      which is 22 x more potent than whole diphtheria toxin. Also, DTaI can
      competitively displace [125I]-insulin with an ED50 of 1.1 x 10(-8) M, which is
      identical to the ED50 of insulin (1.1 x 10(-8) M) and showed limited cross
      reactivity with the IGF-1 receptor (12% displacement of [125I]-IGF-1 with a DTaI
      concentration of 1.1 x 10(-8) M). We have used DTaI to select conjugate-resistant
      clones from the V-79 Chinese hamster fibroblast parental cell line. Conjugate
      resistant variants expressed insulin binding levels ranging from 8.0 +/- 2.0
      fmoles/mg protein down to 3.6 +/- 0.5 fmoles/mg protein while insulin binding in
      the V-79 parental cell line was 11.2 +/- 0.2 fmoles/mg protein. Additionally, a
      number of conjugate resistant clones expressed variable ability to grow in medium
      containing 5% serum. The altered ability of these clones to grow in a serum
      containing medium did not correlate directly with the changes observed for
      insulin binding. One mutant, IV-A1-j, did not grow in a serum-free defined medium
      containing insulin as the predominant mitogen. This IV-A1-j mutant had a lower
      number of insulin receptors, no change in insulin binding affinity, no change in
      the rate of internalization of [125I]-insulin and no apparent difference in
      [125I]-IGF-1 binding. Further, insulin-stimulated sugar transport was similar to
      that observed in the parental cell line. Based on these observations we suggest
      that 1) DTaI elicits its cytotoxicological effects through the insulin receptor
      trafficking pathway, 2) DTaI can be used to isolate cells altered at the level of
      insulin binding and/or action, and 3) signal transduction mechanisms responsible
      for mediating insulin-dependent cell growth can be pursued using mutants such as
      IV-A1-j.

PMID- 1369210
TI  - Comparison of specific rates of hybridoma growth and metabolism in batch and
      continuous cultures.
AB  - For the mouse hybridoma cell line VO 208, kinetics of growth, consumption of
      glucose and glutamine, and production of lactate, ammonia and antibodies were
      compared in batch and continuous cultures. At a given specific growth rate,
      different metabolic activities were observed: a 40% lower glucose and glutamine
      consumption rate, but a 70% higher antibody production rate in continuous than in
      batch culture. Much higher metabolic rates were also measured during the initial
      lag phase of the batch culture. When representing the variation of the specific
      antibody production rate as a function of the specific growth rate, there was a
      positive association between growth and antibody production in the batch culture,
      but a negative association during the transient phase of the continuous culture.
      The kinetic differences between cellular metabolism in batch and continuous
      cultures may be the result of modifications in the physiology and metabolism of
      cells which, in continuous cultures, were extensively exposed to glucose
      limitations.

PMID- 1369211
TI  - Stable production of an analog of human tissue plasminogen activator from
      cultured Drosophila cells.
AB  - We have studied the expression of an analog of human tissue plasminogen
      activator, FK2P, in Drosophila Schneider 2 cells. A number of promoters were
      tested, including the Drosophila metallothionein promoter (MTd), baculovirus
      immediate early promoter (IE), Drosophila copia promoter, mouse metallothionein
      promoter, cytomegalovirus immediate early promoter with or without intron, SV40
      immediate early promoter, and human elongation factor 1 alpha promoter. Two of
      these promoters drove significant expression of FK2P. The MTd promoter is tightly
      regulated and upon induction with copper or cadmium expression of FK2P increases
      as much as 180-fold, accumulating in the culture medium to about 7 micrograms
      FK2P/10(6) cells/day as determined by ELISA. The IE promoter can direct the
      constitutive expression to yield about 0.4 microgram FK2P/10(6) cells/day. The
      production of FK2P in these cell lines remains at about the same level after
      repeated passages, even in the absence of selective pressure. The FK2P
      accumulated in the culture medium is fully active in an assay using a chromogenic
      substrate for serine proteases. Western immunoblot analysis shows that the
      product remains predominantly as single-chain molecules in serum-free medium,
      while in serum-containing medium two-chain material occurs as expected due to the
      presence of plasmin in serum. Judged from the size in Western immunoblots, the
      FK2P produced is glycosylated.

PMID- 1369212
TI  - The growth of Vero cells in suspension as cell-aggregates in serum-free media.
AB  - Vero cell lines, usually considered anchorage-dependent, could be grown as cell
      aggregates in suspension culture with serum-free media. Several different
      combinations of base media gave growth results above 10(6) cells/ml (NCTC
      135:SFRE 199-1; NCTC 135:Waymouth MB 752/1; NCTC 135:RPMI 1640). Insulin was not
      essential for growth and Bovine Serum Albumin could be diluted out of the media
      if linoleic acid was present. The size and density of the aggregates formed
      varied depending on the media used.

PMID- 1369213
TI  - Death of serum-free mouse embryo cells caused by transforming growth factor beta
      1 and effects of nutritional factors.
AB  - Transforming growth factor beta 1 (1 ng/ml) caused death of serum-free mouse
      embryo cells cultured in a medium consisting of a 1:1 mixture of Dulbecco's
      Modified Eagle's medium and Ham's F12 medium supplemented with fibronectin,
      insulin, transferrin, epidermal growth factor, and high density lipoprotein. Cell
      death occurred in the presence of polyunsaturated fatty acids including linoleic
      acid in the absence of selenium. The death could be reversed by adding alpha
      tocopherol to the culture indicating a mechanism involving fatty acid
      peroxidation. Butylated hydroxytoluene was a poor suppressor of cell death in
      contrast to alpha-tocopherol. High density lipoprotein and fatty acid-free
      albumin also suppressed cell death at the level of 20 micrograms/ml and 1 mg/ml,
      respectively. Transforming growth factor beta 1 also caused a low rate of cell
      growth after heat treatment of the cells at 45 degrees C.

PMID- 1369215
TI  - Secondary purification.

PMID- 1369216
TI  - Protein purification by counteracting chromatographic electrophoresis--on the
      disparity of focusing conditions.
AB  - The inconsistency in the focusing data on ferritin by the technique of
      Counteracting Chromatographic Electrophoresis, reported as flow rate vs potential
      gradient has been examined. Voltages in the gel region have been measured and
      analyzed, which are indicative of the fact that the potential gradients in the
      including and excluding gel regions vary from each other; those gradients are
      also different from the potential gradients in the buffer and polyacrylamide plug
      regions. Hence the existence of a constant voltage gradient (across the entire
      column) implied in the literature so far is not quite correct. The ionic strength
      of the carrier buffer, the chemical nature of the buffer components and the
      temperature of experimentation tend to obscure the 'true' data on stable
      accumulation zone formation.

PMID- 1369217
TI  - Separation and purification of IgG1 and IgG2 from IgG-Cohn-II fraction of human
      plasma by pseudobioaffinity chromatography on histidyl-AH-sepharose.
AB  - L-histidine coupled to aminohexyl-sepharose (H-AH) has been used as an affinity
      sorbent to separate IgG from human plasma. Two subclasses IgG1 and IgG2 were
      specifically bound to histidyl-AH-sepharose at pH 7.4 and eluted using 0.2 M and
      1M NaCl. The specificity of the two subclasses were determined by
      immunoelectrophoresis. Quantitative determination of IgG1, IgG2 was carried out
      using radial immunodiffusion technique.

PMID- 1369218
TI  - Amplified expression and large-scale purification of protein G'.
AB  - PCR was used to isolate the gene fragment coding for Protein G' (SpG'), a
      truncated bacterial cell surface protein from Streptococcus G148 which binds to
      the Fc region of IgG and expressed in E. coli [Goward et al. (1990) Biochem. J.
      267: 171-177]. The PCR primer was designed to change the TTG initiation triplet
      to ATG and to incorporate it into an NdeI restriction site (CATATG), allowing the
      gene to be cloned in frame into an NdeI restriction site immediately downstream
      of a trp promoter. Expression of SpG' was estimated as about 30% total soluble
      cell protein which compares very favourably to the less than 1% total soluble
      cell protein obtained from the original system [Goward, et al. (1990) Biochem. J.
      267: 171-177]. Homogeneous SpG' was recovered by a single anion-exchange
      chromatography step on Q-Sepharose FF in a process which avoided use of an
      affinity adsorbent. Even though SpG' consists of almost identical repetitive
      domains from amino acid sequence analysis, different proteolytic sensitivity of
      each domain was observed indicating their structural dissimilarity.

PMID- 1369219
TI  - Techniques for the estimation of cell concentration in the presence of suspended
      solids.
AB  - Measuring cell concentration is of fundamental importance in many biochemical
      processes. However, this measurement is very difficult to make when solid
      particles are present along with the cells. This review examines strategies that
      have been used to estimate cell concentration in the presence of solid particles.

PMID- 1369220
TI  - Screening of insect cell lines for the production of recombinant proteins and
      infectious virus in the baculovirus expression system.
AB  - Eight cell lines derived from the insects Spodoptera frugiperda, Trichoplusia ni,
      Mamestra brassicae, and Estigmene acrea were evaluated for recombinant beta
      galactosidase and infectious virus production following infection with the
      baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV).
      Production was assessed on a specific (per cell and per microgram of uninfected
      cellular protein) and on a volumetric (per milliliter) basis. Cell density was
      found to be an important factor in comparing the cell lines due to a density
      dependent inhibition of specific protein and virus production that appeared to
      result from cell-cell contact. After infection of cells at low-density specific
      beta-galactosidase production per cell would drop between 3- and 6-fold in five
      of the eight cell lines when plated on tissue culture plates at near-confluent
      and confluent cell densities. The cell lines Sf 21 and Sf 9 were least sensitive
      to cell density. After accounting for cell density effects and differences in
      cell size, two cell lines, BTI Tn 5B1-4 and BTI TnM, were identified that were
      superior to the other cell lines, including Sf 21 and Sf 9, in beta-galactosidase
      production. Optimal volumetric and specific beta-galactosidase production from Tn
      5B1-4 and TnM cells was 2-fold and 5-fold higher, respectively, in both cell
      lines than the optimal production from Sf 9 or Sf 21 cells. The Tn 5B1-4 cell
      line also had the highest viability of all the cell lines at 3 days postinfection
      and could be adapted to serum-free media.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369221
TI  - Fluctuations in continuous mammalian cell bioreactors with retention.
AB  - Continuous flow bioreactors with cell retention have been increasingly used for
      the cultivation of mammalian cells. The potential advantages of such bioreactors
      are high cell concentrations and volumetric productivities. In many reported
      cases, these systems have shown fluctuations in cell concentrations of various
      frequency and magnitude. To analyze the dynamics of the fluctuations, a model
      based approach is followed. Simulations showed that large fluctuations in biomass
      resulted in response to fluctuations in the retention ratio when the system is
      operated at high dilution rate and high cell retention. The dependence of cell
      concentration fluctuations on variations in dilution rate and retention ratio was
      established by a cross-correlation statistical analysis on available experimental
      data. The slower dynamics and the fluctuation propensity of retention systems
      suggest that continuous culture without retention is more convenient for kinetic
      studies. In all likelihood, continuous culture with retention can be stabilized
      by controlling both the retention ratio and the dilution rate.

PMID- 1369222
TI  - In situ studies of protein conformation in supercritical fluids: trypsin in
      carbon dioxide.
AB  - The conformation of the monomeric enzyme trypsin has been studied in
      supercritical carbon dioxide. Steady-state fluorescence spectroscopy is used to
      follow the conformation of trypsin in situ as a function of CO2 density. Our
      results show for the first time that protein denaturation can occur during the
      fluid compression step and that the native trypsin is only slightly more stable
      (1.2 kcal/mol) than the unfolded form. These results demonstrate the power of
      fluorescence spectroscopy as a tool for studying protein conformation and
      dynamics in supercritical fluids.

PMID- 1369223
TI  - Mechanical properties of hydrocolloid gels filled with internally produced CO2
      gas bubbles.
AB  - Agar (2%), alginate (1% algin), and kappa-carrageenan (1.5%) gel specimens were
      prepared from mother solutions that contained 0-2.5% sodium bicarbonate (agar and
      carrageenan) or calcium carbonate (alginate). Upon immersion in a citric acid
      bath (0-2%), the carbonate reacted with the diffusing acid to produce numerous
      carbon dioxide bubbles. The compressive strength and deformability of the gas
      filled gels so produced were determined using a Universal testing machine and
      compared with those of pure gels and gels containing the carbonate but not
      subjected to the process after various immersion times. While the agar and
      alginate gels retained considerable mechanical integrity even after several
      hours, the carrageenan gels disintegrated after about 2-5 h. Under similar
      conditions, the number of bubbles produced in the agar gels was about twice that
      in the alginate gels, an observation that cannot be explained solely by
      stoichiometric considerations.

PMID- 1369224
TI  - Electrokinetic isolation of vesicles and ribosomes derived from Serratia
      marcescens.
AB  - Ribosomes and vesicles derived from the bacterium Serratia marcescens were
      separated from each other and from solubles using density gradient
      electrophoresis. Transport relationships were used to determine the
      electrophoretic mobilities of the particles. The effects of convection,
      sedimentation and diffusion were found to be negligible. The electrophoretic
      mobility obtained for the ribosome peak is -7 x 10(-5) cm2/(V.s). Under
      appropriate conditions, two vesicles peaks were obtained, the first with a
      mobility of -4 x 10(-5) cm2/(V.s) and the second with -9 x 10(-6) cm2/(V.s). This
      information can be used to predict the resolution of the separands in large-scale
      electrophoretic separations.

PMID- 1369214
TI  - A free-radical hypothesis for the instability and evolution of genotype and
      phenotype in vitro.
AB  - It has been known for several decades that cultured murine cells undergo a
      defined series of changes, i.e., an in vitro evolution, which includes crisis,
      spontaneous transformation ('immortalization'), aneuploidy, and spontaneous
      neoplastic transformation. These changes have been shown to be caused by the in
      vitro environment rather than an inherent instability of the murine phenotype or
      genotype. Serum amine oxidases were recently identified as a predominant cause of
      crisis. These enzymes generate hydrogen peroxide from polyamine substrates that
      enter the extracellular milieu. This finding implicates free-radical toxicity as
      the underlying cause of in vitro evolution. We propose an oxyradical hypothesis
      to explain each of the stages of in vitro evolution and discuss its significance
      for cytotechnology and long-term cultivation of mammalian cell types.

PMID- 1369225
TI  - Affinity precipitation of proteins by surfactant-solubilized, ligand-modified
      phospholipids.
AB  - The use of ligand-modified phospholipids solubilized in aqueous solution by
      nonionic surfactant for affinity precipitation of proteins is described. Avidin
      was precipitated by contact with solutions in which
      dimyristoylphosphatidylethanolamine (DMPE) functionalized with biotin (DMPE-B)
      was solubilized in octaethylene glycol mono-n-dodecyl ether (C12E8) solutions.
      The nonionic surfactant solubilizes the phospholipid in micelles above its
      critical micelle concentration (CMC) and in small submicellar aggregates below
      this concentration. At C12E8 concentrations significantly exceeding its CMC,
      determined to be about 100 microM, precipitation of avidin by solubilized DMPE-B
      is not observed. In this regime, binding of protein by DMPE-B was monitored by a
      hyperchroic shift in the protein's UV-visible spectrum at 231.5 nm. The data were
      analyzed using a model that considers the four binding sites on the protein to be
      independent and identical in binding strength for DMPE-B. Below the CMC of C12E8,
      precipitation is observed and is monitored by increasing turbidity of the
      solution. The kinetics of precipitation and the aggregate size measured by
      quasielastic light scattering were analyzed using Smoluchowski kinetics and the
      Mie scattering theory. These results help establish more completely the factors
      that influence the precipitation of proteins by ligand-modified phospholipids,
      and they are helpful in specifying conditions for the precipitation of other
      proteins.

PMID- 1369226
TI  - Perfluorooctyl bromide dispersions in aqueous media for biomedical applications.
AB  - In studying perfluorooctyl bromide (PFOB) dispersions in aqueous media, we have
      used two types of surfactant: egg yolk phospholipids (EYP) and polyglycerol
      esters (PGE). Our interest in these dispersions arises from their potential
      biomedical applications as imaging solutions and oxygen-carrying solutions (i.e.,
      blood substitutes). For EYP systems, we have identified the dispersion structure
      as consisting of (a) PFOB droplets (250-nm diameter) stabilized by a phospholipid
      monolayer adsorbed irreversibly at the o/w interface and (b) small empty
      phospholipid vesicles. With both surfactants commercial preparations yielded
      stable systems, while purified samples, being non-dispersible, could not be made
      to act as emulsifiers. In both cases, minor components in the commercial
      surfactant were found to be necessary for the formation of a stable dispersion,
      enabling the transport of the pure surfactant to the PFOB/water interface.

PMID- 1369227
TI  - The solution of hollow fiber bioreactor design equations.
AB  - A methodology for simplifying the solution procedure for hollow fiber bioreactor
      design equations has been described. Such a procedure facilitates decoupling of
      membrane and spongy matrix equations from the tube side equations. The
      equivalence between the reduced equations and the hemodialyzer problem has been
      explicitly obtained.

PMID- 1369228
TI  - Mass transfer in an airlift reactor with a net draft tube.
AB  - Gas-liquid mass transfer in an airlift reactor with net draft tube is
      investigated. The effects of both the ratio of draft tube to reactor diameter and
      the reactor pressure on oxygen transfer are considered. The value of the
      volumetric mass transfer coefficient, kLa, increases with a decreasing diameter
      ratio at higher air flow rates. The correlation of volumetric mass transfer
      coefficient with respect to the true superficial air velocity under different
      reactor pressures is determined. The kLa value decreases with increasing reactor
      pressure.

PMID- 1369230
TI  - Primary structure and function of a dynein motor molecule.

PMID- 1369229
TI  - Cloning and sequence analyses of vasotocin and isotocin precursor cDNAs in the
      masu salmon, Oncorhynchus masou: evolution of neurohypophysial hormone
      precursors.
AB  - We have cloned and determined the nucleotide sequences of cDNAs encoding
      precursors of neurohypophysial hormones, vasotocin (VT) and isotocin (IT), from
      the hypothalamus of masu salmon, Oncorhynchus masou. The deduced amino acid
      sequences of masu salmon VT and IT precursors (proVT-I and proIT-I) are highly
      homologous to those of chum salmon proVT-I and proIT-I, respectively. The VT and
      IT precursors are composed of a signal peptide, hormone and neurophysin (NP), the
      middle portion of which is highly conserved among vertebrates. Both the NPs
      extend about 30 amino acids at the C-terminal. The extended C-terminals have a
      leucin-rich segment in the carboxyl-terminal, as copeptin of vasopressin
      precursor. Southern bot analysis showed the presence of two types of proVT genes
      (proVT-I and proVT-II) and proIT genes (proIT-I and proIT-II) in an individual
      masu salmon, as in a chum salmon. Southern blot analysis with proVT probes
      further suggested that at least two different types of proVT-I genes exist in a
      single masu salmon. Northern blot analysis indicated that proVT-I and proIT-I
      genes are expressed in the hypothalamus, whereas proVT-II and proIT-II genes are
      not expressed. Evolutionary distance between proVT-I and proIT-I genes was
      statistically estimated based on synonymous nucleotide substitution in the coding
      region of the cDNAs. The magnitude of distance between masu salmon proVT-I and
      proIT-I genes suggested that the highly conserved central portion of NPs resulted
      from a gene conversion event. Between masu salmon and chum salmon, evolutionary
      distance for proVT-I genes is about 6-fold larger than that for proIT-I genes.

PMID- 1369231
TI  - Occurrence of a novel 350-kDa serine proteinase in the fluid of porcine ovarian
      follicles and its increase during their maturation.
AB  - Porcine ovary was found to contain enzyme activities hydrolyzing peptide 4
      methylcoumaryl-7-amide (MCA) substrates with a preference for Arg-MCA bond. The
      activities were shown to be present almost exclusively in the follicular fluid
      and to increase several times during follicular maturation. The enzyme
      responsible for these activities is thought to be a serine proteinase as judged
      from its strong inhibition by diisopropylfluorophosphate (DFP), leupeptin and
      antipain. The molecular weight of the native enzyme was electrophoretically
      estimated to be approximately 350,000, the result indicating that the enzyme is
      clearly distinct from plasmin (M(r) = 80,000) and collagenase (M(r) = 30,000
      65,000), both of which are thought to be involved in ovulatory process. The
      substrate specificity of the partially purified enzyme was qualitatively
      different from that of plasmin. These results suggest that the enzyme is a novel
      type of serine proteinase.

PMID- 1369232
TI  - Distribution of APGWa-immunoreactive substances in the central nervous system and
      reproductive apparatus of Helix aspersa.
AB  - The distribution of substances related to the tetrapeptide APGWa was investigated
      in the central nervous system (CNS) and the reproductive apparatus of Helix
      aspersa by immunocytochemistry. In the CNS, APGWa immunoreactive neurons were
      detected in all ganglia except the pedal ganglia. Concerning the mesocerebrum of
      the cerebral ganglia, only neurons of the right mesocerebral lobe reacted
      positively to the antiserum. In the genital apparatus, positive neurons fibres
      were seen in the muscular layer of the penis and, in the gonad, an immunoreactive
      material occurred on the heads of some spermatozoa. On the basis of these
      observations and of previous electrophysiological studies, an implication of
      AGPWa-like peptides in the control of mating behaviour is proposed. The
      significance of the positive reaction of the spermatozoa remains unclear.

PMID- 1369233
TI  - Molecular methods for environmental monitoring and containment of genetically
      engineered microorganisms.
AB  - Plans to introduce genetically engineered microorganisms into the environment has
      led to concerns over safety and has raised questions about how to detect and to
      contain such microorganisms. Specific gene sequences, such as lacZ, have been
      inserted into genetically engineered microorganisms to permit their phenotypic
      detection. Molecular methods have been developed based upon recovery of DNA from
      environmental samples and gene probe hybridization to specific diagnostic gene
      sequences for the specific detection of genetically engineered microorganisms.
      DNA amplification using the polymerase chain reaction has been applied to enhance
      detection sensitivity so that single gene targets can be detected. Detection of
      messenger RNA has permitted the monitoring of gene expression in the environment.
      The use of reporter genes, such as the lux gene for bioluminescence, likewise has
      permitted the observation of gene expression. Conditional lethal constructs have
      been developed as models for containment of genetically engineered
      microorganisms. Suicide vectors, based upon the hok gene have been developed as
      model containment systems.

PMID- 1369234
TI  - The cellulose paradox: pollutant par excellence and/or a reclaimable natural
      resource?
AB  - The various aspects of cellulose as a pollutant are considered in view of its
      lack of toxicity on the one hand and its recalcitrant durable nature on the
      other. The microbial degradation of cellulosics is discussed, and the contrast
      between its success in handling natural cellulosic wastes versus its failure to
      cope with man-made refuse is described. Research carried out in the past decade
      has demonstrated that cellulolytic organisms are provided with cell surface
      multifunctional multienzyme conglomerates, called cellulosomes, which are capable
      of solubilizing solid cellulosic substrates. The intriguing properties of such
      complexes include their cohesive nature, their many enzymatic components, and a
      characteristic glycosylated cellulose-binding, 'scaffolding' component. The
      latter appears to serve as a substrate-targeting carrier, which delivers the
      other (hydrolytic) components to the cellulose. Progress in establishing
      efficient model systems for in vitro solubilization of purified cellulose or
      natural cellulosic substrates has been achieved using purified cellulosome
      preparations, fortified with beta-glucosidase and pectinase. The latter enzymes
      were required in order to alleviate the phenomenon of product inhibition which
      reduces the efficiency of the free cellulosome. Such combined enzyme systems are
      proposed as examples of future tailor-made cellulolytic systems for the
      degradation of natural cellulosics.

PMID- 1369235
TI  - Tissue engineering in the vascular graft.

PMID- 1369237
TI  - The influence of extra-cellular matrix and stroma remodeling on the productivity
      of long-term human bone marrow cultures.
AB  - The stromal cell layer is believed to play an important role in long-term human
      bone marrow cultures (LTHBMCs). At present, neither the role that the stromal
      cell extra-cellular matrix (ECM) plays in influencing stroma behavior is well
      understood nor are the effects of stroma aging. Rapid medium exchanged LTHBMCs
      were established on surfaces precoated with human natural fibronectin and type 1
      rat tail collagen. Although initial adhesion of hematopoietic cells was improved
      by the presence of both ECMs, the overall progenitor and nonadherent cell
      productivity was not improved nor did the stroma grow to confluency faster. Thus,
      the ECMs used did not significantly influence the cell productivity of LTHBMCs.
      To examine the influence of stromal cell layer aging, conditioned medium was
      obtained from the first two weeks of LTHBMCs that was subsequently concentrated
      and used as a medium supplement in a second set of slowly exchanged LTHBMCs. The
      presence of the concentrated conditioned medium (conCM) enhanced the production
      of nonadherent cells three-fold compared with control over an eight week culture
      period. Control cultures that were exposed to conCM after 4 weeks in culture
      significantly improved their cell productivity during the latter 4 weeks of
      culture compared with control. The productivity of cultures exposed to conCM for
      4 weeks dropped significantly when unsupplemented medium was used for the latter
      4 weeks of culture. Interestingly, phytohemagglutin-stimulated leukocyte
      conditioned medium stimulated LTHMBCs in a similar fashion, as did conditioned
      medium from early LTHBMCs. Taken together, these results strongly suggest that
      the stromal cell layer does produce important factors for active hematopoiesis
      during its growth to confluence.

PMID- 1369236
TI  - Primary culture of rat hepatocytes entrapped in cylindrical collagen gels: an in
      vitro system with application to the bioartificial liver. Rat hepatocytes
      cultured in cylindrical collagen gels.
AB  - A static culture model employing cylindrical collagen-hepatocyte gels is reported
      for large scale testing of conditions relevant to the three compartment hollow
      fiber bioartificial liver. High density hepatocyte cultivation was achieved by
      cell entrapment within the collagen-hepatocyte gel. Hepatocyte viability was
      assessed by vital staining, gel contraction, and insulin utilization. Measures of
      hepatocyte-specific function included albumin synthesis, ureagenesis, lidocaine
      biotransformation, and cholate conjugation. Although hepatocyte viability
      remained stable through the seven day incubation period, hepatocyte functions
      were not uniformly preserved. Albumin synthesis remained stable, while
      representative P-450 and conjugation activities decreased with time. This static
      culture system will facilitate the development of a hollow fiber bioartificial
      liver which utilizes cylindrical collagen-hepatocyte gels.

PMID- 1369239
TI  - Inactivation of proteins and other biological macromolecules during
      chromatographic methods of bioseparation.
AB  - The denaturation of proteins and other biological macromolecules such as
      gentamycin, mRNAs, and long-chain fatty acids during their separation by
      different chromatographic techniques is analyzed. Non-conventional techniques
      such as centrifugal partition chromatography are also examined. Particular
      attention is paid to the denaturing mechanisms prevalent under processing
      conditions, and how denaturation may perhaps be alleviated under laboratory
      conditions or during scale-up. The available mechanistic studies shed physical
      insights into the conformational behavior of proteins on chromatographic columns.
      Mechanistic studies of other biological macromolecule separation on columns is
      rare. Numbers for both recovery and purity of the biological product are
      presented wherever available. Scale-up studies are rare, nevertheless, those that
      are presented together do provide significant and valuable information, and may
      be generalized to other systems with caution.

PMID- 1369238
TI  - Tissue engineering science: consequences of cell traction force.
AB  - Blood and tissue cells mechanically interact with soft tissues and tissue
      equivalent reconstituted collagen gels in a variety of situations relevant to
      biomedicine and biotechnology. A key phenomenon in these interactions is the
      exertion of traction force by cells on local collagen fibers which typically
      constitute the solid network of these tissues and gels and impart gross
      mechanical integrity. Two important consequences of cells exerting traction on
      such collagen networks are first, when the cells co-ordinate their traction,
      resulting in cell migration, and second, when their traction is sufficient to
      deform the network. Such cell-collagen network interactions are coupled in a
      number of ways. Network deformation, for example, can result in net alignment of
      collagen fibers, eliciting contact guidance, wherein cells move with
      bidirectional bias along an axis of fiber alignment, potentially leading to a
      nonuniform cell distribution. This may govern cell accumulation in wounds and be
      exploited to control cell infiltration of bioartificial tissues and organs.
      Another consequence of cell traction is the resultant stress and strain in the
      network which modulate cell protein and DNA synthesis and differentiation. We
      summarize, here, relevant mathematical theories which we have used to describe
      the inherent coupling of cell dynamics and tissue mechanics in cell-populated
      collagen gels via traction. The development of appropriate models based on these
      theories, in an effort to understand how events in wound healing govern the rate
      and extent of wound contraction, and to measure cell traction forces in vitro,
      are described. Relevant observations and speculation from cell biology and
      medicine that motivate or serve to critique the assumptions made in the theories
      and models are also summarized.

PMID- 1369240
TI  - Enzyme purification by immobilized metal ion affinity partitioning--application
      to D-hydroxyisocaproate dehydrogenase.
AB  - Extraction and purification of D-2-hydroxyisocaproate dehydrogenase from
      Lactobacillus casei has been studied by means of immobilized metal ion affinity
      partitioning (IMAP) in aqueous two-phase systems. The partition of the enzyme can
      be influenced strongly by inclusion of iminodiacetic acid as chelating ligand
      coupled to polyethylene glycol and loaded with Cu2+ ions into the phase system.
      This applies to polyethylene glycol/dextran as well as polyethylene glycol/salt
      phase systems. An increase in enzyme partition coefficient of up to about 1000
      fold was observed. Based on the mathematic model presented recently by Suh and
      Arnold (1990) approximately 6.4 histidine residues were calculated to be involved
      in the enzyme-metal chelate complex. Direct extraction of the enzyme from both
      cell homogenate and cell debris supernatant proved unsatisfactory due to
      disturbances caused by the presence of cell debris and low molecular weight cell
      components. A combination with a preceding prepurification by a fractional
      precipitation with polyethylene glycol resulted in a strong affinity effect
      accompanied by an efficient purification during IMAP (purification factor of 11
      with a yield of approximately 90%). Based on this step, an efficient downstream
      process can be designed for D-hydroxyisocaproate dehydrogenase.

PMID- 1369241
TI  - A reversed-phase HPLC method for measurement of 5-hydroxymethyl furfuraldehyde
      and furfuraldehyde in processed juices.
AB  - An HPLC method using a reversed-phase macroreticular PLRP-S column and phosphate
      buffer as eluent is described for the analysis of L-ascorbic acid degradation
      products, 5-hydroxymethyl furfuraldehyde and furfuraldehyde, in processed fruit
      juices. Measurement of the levels of 5-HMF and furfuraldehyde in citrus juices
      against time showed the presence of 5-HMF (0.45 mg l-1) even at zero time. An
      assessment on the effect of the additives on the formation of 5-HMF of
      reconstituted single-strength orange juice showed virtually the same results for
      all the samples stored at 4 degrees C and 20 degrees C, irrespective of the
      additive. For citrus juice samples which had been subjected to accelerated
      degradation, those that showed the highest decomposition of L-ascorbic acid,
      produced the highest level of 5-HMF. The presence of furfuraldehyde in any of the
      samples was not detected, probably due to the fact that furfuraldehyde was formed
      in such small amounts which are below the minimum detectability limit of the
      method (0.050 mg l-1).

PMID- 1369242
TI  - Stabilities of antigen and antibody under elution conditions in immunoaffinity
      chromatography using monoclonal antibody.
AB  - In immunoaffinity chromatography using monoclonal antibody, the elution
      conditions of an antigen, recombinant alpha-amylase, were studied. From among
      various conditions, three elution methods that gave fairly good yields of antigen
      activity (pH 2.3-2.5, pH 12.3-12.5 and 0.1 M lithium 3,5-diiodo salicylate [LIS])
      were selected and the stabilities of the antigen and the antibody were analyzed.
      The antigen seemed to be eluted from the immunoadsorbent due to partial
      denaturation of either the antigen or the antibody. LIS seemed to be a specific
      denaturant for the antibody and its action was reversible. In terms of the
      stability of the antigen and repeated use of the immunoadsorbent, LIS seemed to
      be the best reagent for elution in immunoaffinity chromatography.

PMID- 1369243
TI  - Principles of the design and operational considerations of large scale high
      performance liquid chromatography (HPLC) systems for proteins and peptides
      purification.
AB  - This review introduces concepts of design of large scale HPLC systems for
      purification of proteins and peptides. It is addressed to users of large scale
      HPLC systems to aid in system selection and help in customizing the design. Major
      techniques used for large scale HPLC purification of proteins and peptides are
      briefly reviewed. Engineering aspects of system design are discussed in detail.
      The review of selected relevant literature is provided as well as author's
      experience with the existing designs and his own systems. Commercial publications
      have been used in preparation of this review but only the most significant are
      listed as examples. The design process for any new system should be related to
      the performance of existing systems, if possible of a large scale. Laboratory
      data are also very useful in aiding the design process since they provide a lead,
      as to which chromatography techniques may succeed in providing required
      separation levels. The expertise needed for system design and operation comes
      from many areas: protein and peptide chemistry, chromatographic theory, mass
      transfer and hydrodynamics, machine design and material science. All these
      factors have to be blended together during the system design process. The
      controls must ensure flexibility in adapting to changing system configuration,
      depending on the operational requirements for various products. Extensive
      interfacing with the operator during the process run is essential. This work is
      focused mostly on system design and operation for reversed-phase chromatography
      and hydrophobic interaction chromatography, but it also covers aspects associated
      with other chromatographic techniques. The reviewed design principles would also
      apply to design other than HPLC large scale chromatography systems for
      biotechnology and pharmaceutical operations.

PMID- 1369244
TI  - Separation of beta-casein peptides through UF inorganic membranes.
AB  - Ultrafiltration of peptide mixtures is studied under various operating conditions
      (transmembrane pressure, tangential flow-rate) using two ultrafiltration
      inorganic membranes M5 and M1 with molecular weight cut-offs, MWCO 10 and 70 kD,
      respectively. It is shown that the separation of peptides is controlled by a dual
      mechanism: size exclusion and electrostatic repulsion. When the ionic strength is
      high enough to screen out the electrostatic interactions, experimental data are
      in good agreement with a sieving model developed to estimate the intrinsic
      transmission from the molecular weight of a component and from the MWCO of the
      membranes. Although the transmission so found is altered by concentration
      polarisation and pore blocking mechanisms, the results explain the apparent low
      transmission of peptides by ultrafiltration membranes. If the ionic strength of
      the fluid is low, electrostatic interactions can influence the transport
      phenomena, provided that the molecules are highly charged (at pHs away from the
      pI). For attractive interactions, an apparent partition coefficient larger than 1
      is observed. Otherwise, the transmission is lower than predicted by the sieving
      theoretical equation, as if the partition coefficient were smaller than 1.

PMID- 1369245
TI  - Flocculation: an alternative process to ion-exchange chromatography: (A scale-up
      study using recombinant human superoxide dismutase as model protein).
AB  - Flocculation using pellicular charged flocculants was investigated as an
      alternative process to conventional chromatography in purification of recombinant
      proteins using human recombinant superoxide dismutase expressed in E. coli as a
      model system. The removal of pyrogens, proteins, debris and the yield were
      determined. At laboratory scale, the starting conditions were optimized to yield
      a stable solution and the flocculation process fitted into a purification scheme.
      100 L fermentation broth was the initial volume at pilot scale. The process
      parameters determined at the laboratory scale were tested and the results were
      compared to the pilot scale. The method was also compared to an ion-exchange
      chromatography.

PMID- 1369246
TI  - Preparation of peptide mixture with high Fischer ratio from protein hydrolysate
      by adsorption on activated carbon.
AB  - A peptide mixture with a high Fischer ratio (a molar ratio of Val + Leu + Ile to
      Phe + Tyr) was prepared by the adsorptive separation of a casein hydrolysate by
      activated carbon. The effects of the pH and ethanol content of the hydrolysate on
      the Fischer ratio and on the yield of the resulting peptide mixture were
      examined. A peptide mixture with the Fischer ratio of 31.6 was obtained at pH 2.5
      without the addition of ethanol. The Fischer ratio was close to the ratio of the
      infusion solution of free amino acids that is now used for patients with liver
      diseases.

PMID- 1369247
TI  - Recovery of extracellular human insulin-like growth factor-I and II as a fusion
      protein from Escherichia coli culture broth by aqueous two-phase extraction.
AB  - The primary purification of human insulin-like growth factor-I (IGF-I) and IGF
      II, produced extracellularly in Escherichia coli as a fusion to two domains (ZZ)
      derived from staphylococcal protein A, has been studied. First, the partitioning
      of IgG-affinity purified ZZ-IGF-I and ZZ-IGF-II, respectively, to the top phase
      in poly(ethylene glycol)/potassium phosphate aqueous two-phase systems were
      investigated. Thereafter, the extraction of ZZ-IGF-I with a poly(ethylene glycol)
      1500/potassium phosphate system was performed directly in the bioreactor after
      the cultivation. This resulted in a reduction of the cultivation volume more than
      3-fold with a recovery of about 90% of target protein in a poly(ethylene glycol)
      rich phase. The majority of the cells partitioned to the potassium phosphate-rich
      bottom phase, while a smaller fraction was collected at the interface, and/or as
      a densely packed cake on top of the interface. Contaminating proteins were also
      eliminated to some extent, which resulted in an almost 2-fold protein
      purification. Some obvious benefits offered by the aqueous two-phase system in
      the primary purification have been demonstrated: Firstly, the possibility to an
      early process volume reduction and thereby a concentration of the target protein.
      Secondly, a simultaneous protein purification was achieved. From this work it can
      be concluded that aqueous two-phase extraction should be considered as an
      attractive candidate for the primary steps during the design of new purification
      processes for extracellular proteins.

PMID- 1369248
TI  - Direct labeling of antibodies with Tc-99m.

PMID- 1369249
TI  - Adsorption of Streptococcus faecalis on diatomite carriers for use in
      biotransformations.
AB  - Adsorption of cells on particulate carriers is potentially one of the most cost
      effective immobilization techniques available. Diatomite carriers, such as
      Celite, have desirable physical properties, are inexpensive, and are suitable for
      both mycelial and bacterial systems. This work investigated the use of diatomite
      carriers as a biocatalyst support in a packed-bed reactor where L-tyrosine was
      enzymatically decarboxylated using adsorbed, non-growing cells of Streptococcus
      faecalis. Composition of microbial adsorption on different Celite types, with
      mean pore sizes ranging from 0.55 to 22 microns, showed there was no significant
      difference in biomass loading capacity under the conditions used. Using Celite
      560, biomass loadings in a packed-bed reactor varied from 10 to 30 g dm-3 of
      reactor volume, which compares favourably with other adsorption methods. When
      used to decarboxylate L-tyrosine, the reactor was found to have a half-life of 15
      20 h. A combination of enzyme activity loss and slow leakage of biomass from the
      packed-bed reactor was responsible for the decline in conversion. Treatment of
      the S. faecalis cells with glutaraldehyde significantly reduced the enzyme
      activity loss and extended the reactor half-life to 65 h, but had little effect
      on the rate of cell leakage from the reactor. Further work on reduction of cell
      leakage rate seems necessary for evaluation of the system's practicality.

PMID- 1369250
TI  - Expression of virally-transduced mouse tyrosinase in cultured chick embryo cells.
AB  - A cDNA encoding mouse tyrosinase was inserted into a plasmid containing the
      provirus of a replication competent Avian Leukosis Virus (ALV). A viral stock
      produced from the plasmid was used to infect cultured tyrosinase-negative (ca/ca)
      unpigmented chick embryo pigment cells. Five days after infection many cells were
      producing very dark discrete pigment granules. Cultures of tyrosinase positive,
      sex linked albino (sal) pigment cells produced no additional pigmentation. White
      Leghorn pigment cells responded to viral infection like the sal pigment cells.

PMID- 1369251
TI  - Temperature sensitivity of equine herpesvirus isolates: a brief review.
AB  - This article reviews the findings on temperature sensitivity of equine
      herpesvirus isolates with an emphasis on equine herpesvirus 3, etiological agent
      of equine coital exanthema. The hypothesis is presented that the relative
      apathogenic nature of this herpesvirus may be an indirect result of its inability
      to synthesize and/or process glycoproteins needed by the virus to produce
      infectious virions at the normal body temperature of its natural host. It is
      suggested that equine herpesvirus 3 is the more evolved and naturally attenuated
      member of the equine herpesviruses.

PMID- 1369252
TI  - A synthetic peptide representing the thrombin receptor-binding domain enhances
      wound closure in vivo.
AB  - Our studies of alpha-thrombin as a growth factor have led to the development of a
      synthetic peptide (p508) that in vitro competes with thrombin for binding to high
      affinity receptors, and enhances mitogenic activity. To determine if this peptide
      could be used to accelerate wound closure in vivo, full thickness 6 mm dermal
      biopsy wounds on the dorsal skin of anesthetized rats were treated with p508
      peptide, thrombin or PBS as control. At day 7, the p508 treated wound areas were
      20% to 50% smaller than either thrombin or PBS treated wound sites. This suggests
      that p508 enhances aspects of wound healing, and avoids the normal in vivo
      regulatory mechanisms of intact thrombin.

PMID- 1369254
TI  - Effect of inclusion body production on culture turbidity and cell dry weight in
      growing bacterial cultures.
AB  - An approach to the optimization of product yield in an inducible inclusion body
      producing system is presented. Following induction by indoleacrylic acid (IAA) of
      a trpLE-HIVgp41 fusion protein, we found a large increase in culture turbidity
      and single-cell dry weight. After an initial transition phase, new and constant
      values for specific growth rate, single-cell light turbidity, and single cell dry
      weight were achieved, allowing for the determination of optimal conditions for
      product formation.

PMID- 1369253
TI  - Yeast alcohol dehydrogenase bound to membranes: surface and microenvironment
      effects on activity and stability.
AB  - The enzyme, yeast alcohol dehydrogenase, was adsorbed to porous nitrocellulose
      and nylon membranes. The two membranes provide different surface chemistries as
      indicated by the results of the streaming potential, enzyme adsorption, and
      fluorescein isothiocyanate adsorption experiments. The stability of the enzyme,
      as determined by continually measuring the extent of coenzyme reduction as a
      function of time, appeared to be much less for the enzyme adsorbed to the
      positively charged membrane surface. Moreover, the enzyme adsorbed to the
      positively charged membrane was the least responsive to pulses of the reducing
      agent, dithiothreitol, and appeared to exhibit the highest transition temperature
      when subjected to differential scanning calorimetry analysis. These results
      indicate that the entropically spreading process observed for other adsorbed
      proteins may be occurring and the process is more rapid and extensive when enzyme
      is adsorbed to the nylon than the nitrocellulose membrane. In addition to the
      relative stability of the enzyme on two different surfaces being examined, the
      effect of the microenvironment on modulating the activity of the enzyme was
      investigated by using the reversibility of the enzyme-catalyzed reaction as a
      probe of the average local environment of the enzyme. It was found that a
      threshold buffer concentration existed that, once exceeded, the effect of proton
      production by the reaction could be suppressed.

PMID- 1369255
TI  - Genetic engineering approach to toxic waste management: case study for
      organophosphate waste treatment.
AB  - Currently, there has been limited use of genetic engineering for waste treatment.
      In this work, we are developing a procedure for the in situ treatment of toxic
      organophosphate wastes using the enzyme parathion hydrolase. Since this strategy
      is based on the use of an enzyme and not viable microorganisms, recombinant DNA
      technology could be used without the problems associated with releasing
      genetically altered microorganisms into the environment. The gene coding for
      parathion hydrolase was cloned into a Streptomyces lividans, and this transformed
      bacterium was observed to express and excrete this enzyme. Subsequently,
      fermentation conditions were developed to enhance enzyme production, and this
      fermentation was scaled-up to the pilot scale. The cell-free culture fluid (i.e.,
      a nonpurified enzyme solution) was observed to be capable of effectively
      hydrolyzing organophosphate compounds under laboratory and simulated in situ
      conditions.

PMID- 1369256
TI  - Specificity of nucleotide sequence in DNA cleavage induced by D-glucosamine and D
      glucosamine-6-phosphate in the presence of Cu2+.
AB  - 32P-End-labeled restriction fragments derived from pBR322 and pUC9 DNAs were
      reacted with D-glucosamine or D-glucosamine-6-phosphate in the presence of Cu2+,
      and, after being heated at 90 degrees C in aqueous piperidine, the DNA products
      were analyzed on polyacrylamide gels for the sequence-specificity of alkali
      labile cleavaged sites. The intensity of oligonucleotide bands of cleavaged sites
      was directly proportional to the concentration of aminosugars, indicating that
      the DNA cleavage was caused by the action of aminosugars themselves. The
      preferred DNA cleavage sites induced by these aminosugars were identical, both at
      pyrimidine-purine (5'----3') sequences, especially at thymineguanine ones, and to
      some extent at pyrimidine-pyrimidine (5'----3') sequences. The 6-phosphate moiety
      of D-glucosamine did not affect the specificity of DNA cleavage.

PMID- 1369258
TI  - Transgalactosylation products from melibose by the alpha-galactosidase of Absidia
      corymbifera.

PMID- 1369257
TI  - Immobilization of enzymes to porous-bead polymers and silica gels activated by
      graft polymerization of 2,3-epoxypropyl methacrylate.
AB  - Three types of organic polymers and bead-shape silica gels were activated by
      graft polymerization of 2,3-epoxypropyl methacrylate; in some cases, epoxide
      groups on the support surface were modified to NH2 groups. Eight active matrices
      so obtained were assessed as supports for immobilized enzymes using peroxidase,
      glucoamylase and urease. The immobilization yield of protein and specific
      activities of enzymes were better with supports containing NH2 groups than with
      those containing epoxide spacer arms. Maximum enzyme immobilization and storage
      stabilities were obtained with silica-gel beads activated by graft polymerization
      of 2,3-epoxypropyl methacrylate. With all eight matrices tested, the immobilized
      enzymes showed good stability with not less than 82% of the original activity
      persisting after 28 days. The developed matrices have potential for use in
      process-scale biotechnological operations.

PMID- 1369259
TI  - Oligonucleotidase activity of phosphodiesterase from the fruit body of Flammulina
      velutipes.
AB  - A phosphodiesterase (EC 3.1.4.1) was purified to homogeneity from the fruit body
      of Flammulina velutipes. The enzyme had considerable activity toward
      oligonucleotides. The Km values were 0.66 mM for ApA, 2.47 mM for (Ap)2A, and
      3.03 mM for (Ap)3A. The enzyme hydrolyzed oligodeoxyribonucleotides as well as
      oligoribonucleotides. The oligoribonucleotides bearing a phosphate residue at the
      3' end were not hydrolyzed by the enzyme. The enzyme hydrolyzed the
      oligoribonucleotides exonucleolytically from the 3' to 5' end. Thus the PDase of
      F. velutipes is considered to function in vivo as an oligonucleotidase (EC
      3.1.13.3), which efficiently converts oligonucleotides to 5'-mononucleotides in
      the cell.

PMID- 1369261
TI  - Solubility as a function of protein structure and solvent components.
AB  - This review deals with ways of stabilizing proteins against aggregation and with
      methods to determine, predict, and increase solubility. Solvent additives
      (osmolytes) that stabilize proteins are listed with a description of their
      effects on proteins and on the solvation properties of water. Special attention
      is given to areas where solubility limitations pose major problems, as in the
      preparation of highly concentrated solutions of recombinant proteins for
      structural determination with NMR and X-ray crystallography, refolding of
      inclusion body proteins, studies of membrane protein dynamics, and in the
      formulation of proteins for pharmaceutical use. Structural factors relating to
      solubility and possibilities for protein engineering are analyzed.

PMID- 1369260
TI  - Improvement in microbial production of L-tyrosine by gene dosage effect of aroL
      gene encoding shikimate kinase.

PMID- 1369262
TI  - D-ribulokinase from Klebsiella pneumoniae for continuous production of D-(-)
      ribulose-5-phosphate.
AB  - The production of D-ribulose-5-phosphate in an enzyme membrane reactor was
      examined. Phosphoryl transfer from ATP to D-ribulose was catalysed by D
      ribulokinase isolated from Klebsiella pneumoniae. For production of D-ribulose-5
      phosphate the phosphoryl donor ATP was used either in stoichiometric or in
      catalytic amounts. Using catalytic amounts of ATP requires a second enzyme, e.g.
      pyruvate kinase, to regenerate ATP. The kinetic parameters for D-ribulokinase and
      pyruvate kinase were determined to calculate the performance of an enzyme
      membrane reactor for continuous production of D-ribulose-5-phosphate. Both
      processes operated for more than 200 h. Regardless of whether ATP was used in
      catalytic or stoichiometric amounts, about the same production parameters were
      determined. In continuous production space/time yields of 117 g (with ATP
      regeneration) and 103 g (without ATP regeneration) of D-ribulose-5-phosphate l -1
      per day were reached.

PMID- 1369263
TI  - Quinoproteins: a new class of enzymes with potential use as biosensors.
AB  - The field of the enzymology of quinoproteins is still in its infancy. As more
      progress is made toward understanding the mechanisms of catalysis and electron
      transfer by protein-bound PQQ, it will become possible to more logically design
      specific quinoprotein-based electrodes. The characterization of new quinoproteins
      is progressing at a rapid rate. As new quinoproteins are found, the potential
      range of applications for use of these enzymes in biosensors will increase as
      well.

PMID- 1369264
TI  - Development of a real-time glucose biosensor by enzyme immobilization on the
      quartz crystal microbalance.

PMID- 1369265
TI  - Affinity chromatography supports: a look at performance requirements.
AB  - Because of its high selectivity, affinity chromatography is a preferred tool in
      the downstream processing of high-value proteins and peptides of therapeutic
      interest. This review examines the affinity supports currently available, and
      investigates the performance characteristics and properties required of the
      support matrices for improved affinity-based supports for large-scale
      purification of biomolecules. Parameters for optimizing an affinity
      chromatographic process, and the advantages of affinity-based separation for
      scaled-up systems are highlighted.

PMID- 1369266
TI  - Production of 5'-ribonucleotides by enzymatic hydrolysis of RNA.
AB  - Study of optimal operational conditions for RNA enzymatic hydrolysis to obtain 5'
      ribonucleotides has been carried out. RNA from brewer's yeasts, obtained by
      ammonium extraction, was hydrolysed by a partially purified 5'-phosphodiesterase
      from barley rootlets. Temperature of 60 degrees C and pH 7 have been determined
      as the best operational conditions. Low RNA initial concentration (approximately
      0.1%) and reaction time (approximately 1 h) have been identified as necessary to
      obtain a good yield of 5'-ribonucleotides.

PMID- 1369267
TI  - A simple method for elucidating structures of galactomanno-oligosaccharides by
      sequential actions of beta-mannosidase and alpha-galactosidase.

PMID- 1369268
TI  - Transfection of mouse cells with thymidine kinase gene of herpes simplex virus.
AB  - A mouse cell line (LP1-1) was established from the murine L cells deficient in
      thymidine kinase (L-M(TK-] by prolonged selective culture on the hypoxanthine
      aminopterine-thymidine (HAT) medium following transfection with the thymidine
      kinase gene of herpes simplex virus type-I (HSVTK). Southern blot analysis has
      shown that the viral TK gene was integrated into one of the chromosomal loci by a
      single copy. From this established cell line, the 5-bromo-2-deoxyuridine (BrdU)
      resistant revertant was brought out at a frequency of 1 x 10(-6) and from these
      BrdU resistant revertants (LP1BU), one out of 1 x 10(5) cells could return to the
      HAT-resistant phenotype. The established LP1-1 cell line showed a typical
      biphasic nature of DNA synthesis as determined by the 3H-thymidine incorporation
      test. The activity of thymidine kinase was shown to be equivalent to that of the
      DNA polymerase-alpha when the whole nuclear fraction or the nuclear matrix were
      used for examination. These results indicate that the transfected viral TK gene
      can be expressed under the normal cell-cycle regulation and its gene product can
      act as a component of the multienzyme complex which is responsible for DNA
      replication.

PMID- 1369269
TI  - Integration of heterologous genes into the chromosome of Saccharomyces cerevisiae
      using a delta sequence of yeast retrotransposon Ty.
AB  - Distribution of a delta (delta) sequence of the Ty element on a chromosome of the
      yeast Saccharomyces cerevisiae was analysed by pulsed-field gel electrophoresis.
      More than 100 copies of the delta sequence were nonrandomly distributed on the
      chromosome. Using the delta sequence as a recombination site, mouse alpha-amylase
      and human beta-endorphin genes were introduced into the chromosomal DNA. The
      integration occurred on a particular chromosome in each case and the copy number
      was estimated as three to five. It was also found that single- or multi-copy
      integration occurred at a single or multiple sites on the particular chromosome.
      The integrants secreted alpha-amylase and beta-endorphin by three-to fivefold
      compared with single-copy integrants. This type of integration was mitotically
      stable over a period of 50 generations under non-selective conditions.

PMID- 1369270
TI  - Animal cell culture and the AIDS problem.

PMID- 1369271
TI  - A human-human hybridoma secreting anti-Pseudomonas aeruginosa exotoxin-A
      monoclonal antibody with highly potent neutralizing activity.
AB  - A hybridoma secreting human monoclonal antibody (MAB) against Pseudomonas
      aeruginosa exotoxin A (PEA) was constructed by fusing Epstein-Barr virus
      transformed peripheral blood lymphocytes with human B lymphoblastoid cell line
      TAW-925. The human-human hybridoma stably produced human IgG2 MAB at the rate of
      0.4-0.5 microgram/ml per 10(6) cells per day for more than six months, and the
      MAB was capable of neutralizing the in vitro cytotoxic and in vivo lethal effects
      of PEA with approximately 100- and 70-fold, respectively, higher activity than
      serum polyclonal antibody preparations.

PMID- 1369273
TI  - Production of human tissue-type plasminogen activator in different mammalian cell
      lines using an Epstein-Barr virus vector.
AB  - Human tissue-type plasminogen activator (t-PA) cDNA inserted into an Epstein-Barr
      virus (EBV) derived expression vector was transfected into human HeLa, 293, K-562
      and hamster CHO-K1 cells and the expression of t-PA was studied. The best t-PA
      producing cell clones were found among CHO-K1 cells (up to 11 micrograms d-1 per
      10(6) cells). However, HeLa and 293 cells were most efficiently transfected, e.g.
      about 70% of the selected cell clones were t-PA positive. The vector DNA copy
      numbers correlated with the mRNA levels and the protein levels for all cell lines
      analysed, with the exception for the K-562 cell line, where the production of t
      PA was very low. The results obtained indicated that the highest expression
      levels were achieved in low density cultures.

PMID- 1369272
TI  - Characterization of a temperate actinophage, MPphiWR-1, capable of infecting
      Micromonospora purpurea ATCC 15835.
AB  - A temperate actinophage was isolated from soil using the gentamicin-producing
      microorganism, Micromonospora purpurea ATCC 15835 as host. The characterization
      of the phage represents the initial step in its development as a cloning vector.
      The phage isolated, MPphiWR-1, formed red- to purple-pigmented turbid plaques.
      Cells isolated from these plaques were resistant to superinfection with lytic
      mutants of MPphiWR-1. Southern blots of genomic DNA from a resistant culture
      showed that MPphiWR-1 integrated into the host genome. The phage was UV- or
      Mitomycin C-inducible. The integration, resistance to superinfection and
      inducibility indicated a lysogenic relationship with the host. Using MPphiE-RCPM,
      a lytic derivative, the phage host range was demonstrated to include members of
      three genera: one species each of Ampullariella and Catellatospora, and 12
      species of Micromonospora. The phage belonged to Ackerman's B1 morphotype having
      an isometric head and a flexible noncontractile tail. The density of the phage
      was 1.525 g/cc. Restriction site mapping demonstrated that the phage DNA was 57.9
      kb long and had cohesive ends. Using EDTA enrichment, viable mutants with
      deletions of at least 3.5 kb were isolated and mapped. Phage adsorption,
      sensitivities and plating efficiency were investigated. Non-liposome PEG-mediated
      transfection was demonstrated.

PMID- 1369274
TI  - Regulation of alternative splicing.

PMID- 1369276
TI  - The utility of streptomycetes as hosts for gene cloning.

PMID- 1369275
TI  - Structure and function of the nuclear receptor superfamily for steroid, thyroid
      hormone and retinoic acid.

PMID- 1369277
TI  - Micro-organisms as fertilizers and pest control agents in agricultural crops.
AB  - Micro-organisms can potentially supplement or replace the use of chemical
      fertilizers and pesticides in many agricultural cropping systems. Their increased
      use may reduce the need for nitrogen and phosphorus fertilizers, particularly in
      legume and cereal crops, and provide a more ecologically sound method of
      controlling pests and phytopathogens. Recombinant DNA technology offers the
      potential to extend and improve these applications. However, genetically modified
      micro-organisms may occasionally themselves pose environmental risks. Model
      ecosystems such as intact soil-core microcosms may be useful for both testing
      efficacy and evaluating environmental risk prior to proceeding with field trials.

PMID- 1369278
TI  - Expression of human lymphotoxin in Namalwa KJM-1 cells adapted to serum-free
      medium.
AB  - A Namalwa cell line, KJM-1, which was adapted to serum-free medium is thought to
      be a good host cell line for recombinant DNA technology. We previously reported
      the expression of human beta-interferon (beta-IFN) in Namalwa KJM-1 (Miyaji,
      1989a). The utility of Namalwa KJM-1 for expression of foreign genes was further
      examined. As a target gene to be expressed, human lymphotoxin (hLT) cDNA was
      used. It was engineered for expression in Namalwa KJM-1 using a simian virus 40
      (SV40)-based expression vector pAGE107 (Miyaji, 1989a). It contains all
      components necessary for the expression of cDNA in mammalian cells. The
      expression vector was introduced into Namalwa KJM-1 by electroporation. Among the
      transformants, clone 7 was further examined for the expression of hLT in serum
      free medium. The production level of hLT was augmented with the increase of the
      cell density. Thus it was further indicated that Namalwa KJM-1 is useful for
      production of foreign gene products.

PMID- 1369280
TI  - Sense-antisense complementarity of hormone-receptor interaction sites.

PMID- 1369279
TI  - A human hybrid hybridoma producing a bispecific monoclonal antibody that can
      target tumor cells for attack by Pseudomonas aeruginosa exotoxin A.
AB  - By fusing a human hybridoma producing an IgG2 kappa antibody against human A431
      epidermoid carcinoma cells with an Epstein-Barr virus-transformed human B
      lymphocyte producing an IgG2 kappa antibody against Pseudomonas aeruginosa
      exotoxin A, we established a hybrid hybridoma producing a bispecific monoclonal
      antibody reacting with both A431 cells and the exotoxin. Human IgG was purified
      from the culture supernatant of the hybrid hybridoma, and the bispecific
      monoclonal antibody in the IgG preparation was further separated from the two
      parental antibodies by hydroxyapatite high-performance liquid chromatography. The
      human bispecific monoclonal antibody thus obtained efficiently targeted the
      antibody-reactive cells, A431, for attack by the exotoxin in vitro.

PMID- 1369281
TI  - Use of hollow fiber technology for large scale production of viruses and viral
      antigens.

PMID- 1369282
TI  - Improved production of heterologous protein from Streptomyces lividans.
AB  - Protein-secreting procaryotic host organisms are currently being sought as
      alternatives to Escherichia coli for recombinant processing. In this study we
      examined how manipulation of the cultivation conditions can enhance heterologous
      protein production by Streptomyces lividans. The recombinant S. lividans used in
      this study expressed and excreted a Flavobacterium enzyme capable of hydrolyzing
      organophosphates. Initial shake-flask studies demonstrated that supplementing
      Luria-Bertani medium with moderate amounts of glucose (30 g/l), led to improved
      enzyme production. In fermentor studies with controlled pH, a further twofold
      increase in production was observed when glucose was fed continuously as compared
      to batch cultivation. This improved production in the glucose-fed culture may be
      related to a reduced accumulation of acids. Continuous feeding of both glucose
      and tryptone led to a further sixfold increase in production. In addition to
      enhancing production 25-fold, the efficiency of enzyme production and the
      specific activity of the excreted enzyme were also improved by glucose and
      tryptone feeding. These results demonstrate that in addition to genetic
      manipulations, optimization of cultivation conditions can lead to significant
      improvements in the production of heterologous proteins from Streptomyces.

PMID- 1369283
TI  - Endonuclease-free, protoplast-forming enzyme preparation and its application in
      fungal transformation.
AB  - An endonuclease-free, protoplast-forming enzyme complex was prepared from the
      "snail enzyme." The purified preparation has high protoplast-forming activity
      comparable to the crude enzyme complex without destroying circular plasmid DNA.
      Furthermore, a higher transformation rate was achieved by the application of the
      endonuclease-free enzyme complex in both yeast and filamentous fungal vector-host
      systems.

PMID- 1369284
TI  - Occurrence of aminoglycoside phosphotransferase subclass I and II structural
      genes among Enterobacteriaceae spp. isolated from meat samples.
AB  - 3'-Aminoglycoside phosphotransferase [APH(3')] enzymes are a group responsible
      for resistance to the antibiotics kanamycin (Km) and neomycin (Nm) in bacteria.
      Escherichia coli ECT24, originally isolated from a meat sample, harboured an 83
      kb conjugative R-plasmid (pRPJ24) that carries transferable resistance to Km and
      Nm. Plasmid pRPJ24 was transferred by conjugation to Enterobacter cloacae 94R,
      which was used as the source of plasmid DNA in development of a probe for the Km
      resistance determinant. Random cloning of BamHI and HindIII double-digest
      restriction fragments of pRPJ24 in the pUC18 vector plasmid produced clones
      resistant to both Nm and Km carrying a 1.9-kb DNA insert. Southern hybridization
      of pRPJ24 cloned chimeric plasmid DNA (pKPJ94) showed homology with the APH(3')II
      gene from transposon Tn5. A PstI digest of pKPJ94 produced a 920-bp fragment
      which hybridized with the APH(3')II structural gene, and was used as a DNA probe
      for the APH(3')II subclass gene. A 980-bp BamHI fragment from plasmid pGH54
      carrying the APH(3')I gene from transposon Tn903 was used as a subclass I probe.
      Total DNA from 206 randomly screened Km-resistant Enterobacteriaceae isolates
      from raw ground beef and chicken meat samples were examined for the occurrence of
      APH(3') subclass I and II using non-radioactively-labelled DNA probes. Thirty-six
      percent and 60% of the isolates examined carried subclass I and II resistances,
      respectively, in the isolates from chicken meat samples. The corresponding values
      for bacterial strains from raw ground beef samples were 51% and 72%,
      respectively. Four percent of the resistant bacterial isolates from chicken
      samples did not display homology to either probe.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1369285
TI  - Applications of thin layer chromatography, high performance liquid chromatography
      and mass spectrometry in the fermentation and isolation of the antibiotic
      nybomycin.
AB  - Thin layer chromatography (TLC), high performance liquid chromatography (HPLC)
      and mass spectrometry (MS) methods have been developed for the analysis of the
      antibiotic nybomycin, its derivatives deoxynybomycin and nybomycin acetate,
      during the fermentation and isolation of nybomycin. Using a quantitative HPLC
      based assay, the time course of nybomycin production (nybomycin titers) in 1000
      liter fermentations was determined. Desorption chemical ionization mass
      spectrometry (DCI/MS) of standard nybomycin samples, fermentation broth samples
      and purified fractions suggested the co-production of deoxynybomycin which was
      not reported previously from this organism. TLC and HPLC were used to confirm the
      presence of deoxynybomycin in the crude extracts of fermentation broths.

PMID- 1369286
TI  - Overloaded hollow-fiber liquid chromatography.
AB  - Liquid chromatography in hollow fibers can separate solutes like flavors and
      proteins by using a stationary phase of organic solvent, sometimes containing
      reversed micelles. Such separations, which have a much smaller pressure drop than
      equivalent separations in packed beds, show dispersion consistent with
      chromatographic theories at low flows and dilute feeds. These separations behave
      less predictably at high flows and concentrated feeds, which overload the hollow
      fibers. The results for flavors correlate well with the Graetz number, consistent
      with available theories of chromatography and adsorption. The results for
      proteins correlate poorly with the Graetz number but better with a dimensionless
      flux based on facilitated diffusion in the stationary phase.

PMID- 1369287
TI  - pIF21, a versatile donor of transposons Tn1, Tn5 and Tn7 for tagging and
      mobilizing cryptic and non-selectable plasmids.
AB  - A plasmid, pIF21, has been constructed that is able to donate transposons Tn1,
      Tn5 and Tn7. The transposons are located on a temperature-sensitive derivative of
      the incP1 plasmid pRP1, which is transferable to a wide range of Gram-negative
      genera.

PMID- 1369288
TI  - Cloning vectors derived from Streptomyces niveus plasmid pSN2.
AB  - Two high copy number, broad host range, general purpose cloning vectors, pLG5 and
      pLG10, derived from the unstable Streptomyces niveus plasmid pSN2 are described.
      pLG5 (5.5 kb) and pLG10 (6.5 kb) both carry the thiostrepton resistance (TsrR)
      and lethal zygosis (Ltz+) markers and have single cloning sites within a non
      essential region and the tsr gene. pLG505 (7.4 kb) was constructed by cloning the
      viomycin resistance (vph) gene into the single BamHI site of pLG5 to give a
      further vector with insertion and replacement sites which inactivate either the
      TsrR or VioR functions.

PMID- 1369289
TI  - The pFF plasmids: cassettes utilising CaMV sequences for expression of foreign
      genes in plants.
AB  - A plant expression cassette was constructed using the cauliflower mosaic virus
      35S 5' regulatory region with the enhancer duplicated and the 35S polyadenylation
      signal. Insertion of a polylinker between the transcription initiation and
      polyadenylation sites allows for easy cloning of genes. To test the usefulness of
      the cassette chimeric bacterial genes were prepared. The constructs were
      introduced into Nicotiana tabacum suspension culture cells by the particle
      bombardment process. Expression of the beta-glucuronidase reporter gene was
      verified by histochemical staining. Stable kanamycin and hygromycin resistant
      transgenic lines were obtained after introduction of chimeric genes encoding the
      enzymes neomycin phosphotransferase and hygromycin B phosphotransferase,
      respectively. The number of stable transformants was approximately 2% of the
      cells that transiently expressed the beta-glucuronidase reporter gene.

PMID- 1369290
TI  - Immobilization of penicillin G acylase on methacrylate polymers.
AB  - Macroporous weak cation-exchange methacrylate polymers were synthesized for the
      immobilization of penicillin G (Pen G) acylase. The role of certain factors such
      as pore-generating solvent, cross-linking agent, cross-linking density, and
      comonomer, in enzyme adsorption and expression was studied. Kerosene was a
      superior pore-generating solvent to paraffin oil. Ethylene glycol dimethacrylate
      and acrylic acid served as the best cross-linking agent and comonomer,
      respectively, in the systems studied. 80.3% of the activity of the enzyme
      adsorbed onto polymer beads prepared with 0.05 mol of acrylic acid (polymer PM
      39) was expressed. Properties of the Pen G acylase, immobilized on PM-39 by
      adsorption and cross-linking with glutaraldehyde (IME-PM-39) were studied. The
      optimum pH, optimum temperature and Km of Pen G acylase shifted from 8.0 to 7.5
      7.8, 50 degrees C to 55 degrees C and 0.038 mol dm-3 to 2.4-3.0 mol dm-3,
      respectively, as a result of immobilization on PM-39. IME-PM-39 was used
      repeatedly for 15 cycles in the production of 6-amino penicillanic acid (6-APA).

PMID- 1369291
TI  - Purification, properties and recognition sequence and cleavage site
      determinations of restriction endonuclease from Acetobacter pasteurianus IFO
      13753 (ApaLI).
AB  - A new restriction endonuclease, designated as ApaLI, was purified from cell-free
      extracts of Acetobacter pasteurianus IFO 13753 by streptomycin treatment,
      ammonium sulfate fractionation, combined column chromatographies on heparin
      Sepharose CL-6B and DEAE-Sepharose CL-6B and Fast Protein Liquid Chromatography
      on Mono Q HR 5/5. The purified enzyme was homogeneous on polyacrylamide gel disc
      electrophoresis. The molecular weight of the purified enzyme was calculated as
      26,000 daltons by gel filtration using Sephadex G-200, and the isoelectric point
      of the purified enzyme was 4.8 by ampholine sucrose-density gradient isoelectric
      focusing. The purified enzyme cleaved lambda, Ad2, SV40, M13mp18 RF 1, psi X174
      RF I and pBR322 DNAs at 4, 7, 0, 0, 1 and 3 sites, respectively. The purified
      enzyme worked best at 37 degrees C and pH 8.0 in a reaction mixture (50
      microliters) containing 1.0 micrograms lambda DNA, 10mM Tris-HCl, 7 mM 2
      mercaptoethanol, 7 mM MgCl2 and 25mM NaCl. However, the purified enzyme did not
      require NaCl necessarily for the enzyme reaction. The purified enzyme recognized
      the palindromic hexanucleotide DNA sequence, 5'-GTGCAC-3' and cut between G and
      T, producing a 5'-cohesive tetranucleotide extension.

PMID- 1369292
TI  - Purification, properties and determinations of recognition sequence and cleavage
      site of restriction endonuclease from "Agrobacterium gelatinovorum" IAM 12617, a
      marine bacterium (AgeI).
AB  - A new restriction endonuclease, designated as AgeI, was purified from cell-free
      extracts of a marine bacterium, "Agrobacterium gelatinovorum" IAM 12617 by
      streptomycin treatment, ammonium sulfate fractionation, combined column
      chromatographies on heparin-Sepharose CL-6B and DEAE-Sepharose CL-6B and FPLC on
      Mono Q (HR 5/5) and Superose 12 (HR 10/30). The purified enzyme was homogeneous
      on SDS-polyacrylamide gel disc electrophoresis and free from other phosphatase
      and exonuclease activities on ligation-recutting test. The relative molecular
      mass of the enzyme was 24,000 daltons by SDS-polyacrylamide gel disc
      electrophoresis. The gel filtration using Superose 12 (HR 10/30) gave the same
      calculation (23,000 daltons). These data indicated that the enzyme is a monomer.
      The isoelectric point of the enzyme was 6.5. The purified enzyme cleaved lambda
      and Ad2 DNAs at 10 or more and 5 sites, respectively. However, the purified
      enzyme did not cleave SV40, phi X174 RF I, M13mp 18 RF I or pBR322 DNAs. pBR328
      DNA was cleaved at 1 site by the purified enzyme. The purified enzyme worked best
      at 37 degrees C and pH 7.5 in a reaction mixture (50 microliters) containing 1.0
      micrograms lambda DNA, 10 mM Tris-HCl, 7 mM 2-mercaptoethanol, 7 mM MgCl2 and 50
      mM NaCl. The purified enzyme did not require monovalent cations necessarily for
      the enzyme reaction. The enzyme recognized the palindromic hexanucleotide DNA
      sequence 5'-ACCGGT-3' and cut between A and C, producing a 5'-cohesive
      tetranucleotide extension.

PMID- 1369293
TI  - Isolation and characterization of opioid antagonist peptides derived from human
      lactoferrin.
AB  - Peptides with affinity for opioid receptors were found in an artificially methyl
      esterified peptic digest of human lactoferrin. Three active peptides were
      purified by two steps of reverse-phase high-performance liquid chromatography.
      Their structures were Tyr-Leu-Gly-Ser-Gly-Tyr-OCH3, Arg-Tyr-Tyr-Gly-Tyr-OCH2, and
      Lys-Tyr-Leu-Gly-Pro-Gln-Tyr-OCH3, which respectively correspond to the methyl
      esters of residues 318-323, 536-540, and 673-679 of human lactoferrin. The IC50
      values of these peptides were 15, 10 and 23 microM, respectively, in a
      radioreceptor assay in the presence of 1 nM [3H]naloxone. In the myenteric plexus
      preparation of the longitudinal muscle of guinea pig ileum, the individual
      peptides had no opioid agonist activities, but they antagonized [Met5]enkephalin
      and morphiceptin when they were at a concentration of 10(-6)-10(-5) M, suggesting
      that these were the opioid antagonist peptides. These three opioid antagonist
      peptides were named lactoferroxin A, B and C, after casoxin, the opioid
      antagonist peptide derived from bovine kappa-casein. Concerning the antagonist
      activities of lactoferroxins for opioid receptor sub-types, lactoferroxin A
      showed preference for mu-receptors, while lactoferroxin B and C had somewhat
      higher degrees of preference for kappa-receptors than for mu-receptors. A study
      of the structure-activity relationship of the three lactoferroxins and their
      synthetic analogues showed that these opioid antagonist peptides derived from
      food protein could be expressed by the general formula XA-Tyr-XB-Tyr-OCH3. An
      amino acid in position XA may affect the specificity of the antagonist peptide
      for opioid receptor sub-types.

PMID- 1369294
TI  - Are B.T.K. plants really safe to eat?

PMID- 1369295
TI  - Secretion of Aspergillus oryzae alkaline protease in an osmophilic yeast,
      Zygosaccharomyces rouxii.
AB  - To produce Aspergillus oryzae alkaline protease (Alp) in an osmophilic yeast
      Zygosaccharomyces rouxii, we constructed an expression plasmid consisting of the
      Z. rouxii glyceraldehyde-3-phosphate dehydrogenase (GAPDH) promoter, the prepro
      Alp cDNA of A. oryzae, the whole sequence of Z. rouxii plasmid pSR1, and the G418
      resistant gene. The resulting plasmid, when introduced into Z. rouxii cells,
      directed the secretion of a large amount (about 300 mg/l) of Alp into the culture
      medium. The N-terminus and specific activity of the enzyme were identical to
      those of A. oryzae Alp.

PMID- 1369296
TI  - A novel human hepatoblastoma cell line (HuH-6KK) with rapid growth in serum-free
      medium without extracellular matrix.
AB  - A novel human hepatoblastoma cell line (HuH-6KK) with a high growth rate in a
      serum-free medium without extracellular matrix was developed from an original
      one, HuH-6 c15 (HuH). The original HuH cells (38 passages) did not proliferate
      well in RPMI 1640 medium containing 20% fetal calf serum (FCS). The HuH cells
      (HuH-6KK) with a high growth rate were selected by culturing them in an enriched
      RDF containing 20% FCS and 0.01% mucous polysaccharide (spirulinan) isolated from
      a blue-green alga, Spirulina subsalsa. The HuH-6KK cells showed a rapid growth in
      serum-free eRDF medium containing insulin, transferrin, ethanolamine, and
      selenite (eRDF-ITES medium) without fibronectin. The proliferation of the
      original HuH cells was also observed in the eRDF-ITES medium, but the growth was
      slow compared with the HuH-6KK cells. In the medium without ITES, the growth of
      the HuH-6KK and original HuH cells was slow. Among the ITES ingredients, insulin
      promoted the growth of HuH-6KK cells the most.

PMID- 1369297
TI  - Calmodulin antagonistic action of KS-504a, a novel metabolite of the fungus
      Mollisia ventosa.
AB  - KS-504a inhibited bovine brain calmodulin-dependent cyclic nucleotide
      phosphodiesterase (CaM-PDE) with an IC50 value of 122 microM. The inhibition was
      reversed by a high concentration of calmodulin. Calmodulin-independent activities
      of the enzyme were not affected by the compound at the same concentration ranges.
      Ca2(+)-dependent interaction of the compounds with calmodulin was shown using
      hydrophobic fluorescence probes. These data indicated that the compound exerted
      its effects on CaM-PDE by interacting with calmodulin. KS-504a also inhibited
      other calmodulin-dependent enzymes at different concentration ranges; myosin
      light chain kinase was inhibited at the lowest concentrations with an IC50 value
      of 6.3 microM. The inhibition mechanism was competitive with respect to
      calmodulin and non-competitive to ATP.

PMID- 1369298
TI  - Regulated expression of heterologous genes in Bacillus subtilis using the Tn10
      encoded tet regulatory elements.
AB  - The Escherichia coli-derived tet regulatory elements from Tn10 have been used to
      construct vectors allowing the regulated, inducible, high-level expression of
      foreign genes in Bacillus subtilis. While the wild-type tet promoters are
      inactive in B. subtilis, a synthetic mutant tet sequence with improved promoter
      consensus sequences and upstream poly A blocks shows activity in B. subtilis. The
      expression of an indicator cat gene is inducible by sublethal amounts of
      tetracycline, indicating that the Tet repressor protein and the tet operator
      sequences are functional. However, the inducibility and maximal expression are
      not sufficient in this construct. To improve these properties a tet operator
      sequence was placed between the -35 and -10 boxes of the B. subtilis-derived very
      strong xyl promoter. In the presence of a tetR gene this construct is about 100
      fold inducible and has high promoter strength, but some basal expression. This is
      avoided by placing a second tet operator downstream resulting in no detectable
      basal expression at the expense of reduced inducibility. Using the system with a
      single tet operator inducible expression of glucose dehydrogenase from B.
      megaterium was obtained at a very high level, and inducible expression of human
      single-chain urokinase-like plasminogen activator was achieved at the same level
      as in E. coli. Unlike in E. coli, the product was not degraded up to 4 h after
      induction in B. subtilis. These results demonstrate that the regulated expression
      vector described here should be very useful for production of foreign gene
      products from B. subtilis cultures.

PMID- 1369299
TI  - HAF, hepatoma aggregation factor produced by Streptomyces sp. strain No. A-6143.
AB  - We searched for a new cell aggregation factor for hepatoma AH109A cells, and
      found one we called HAF in the culture filtrate of Streptomyces sp. strain No. A
      6143 isolated from a soil sample. HAF was purified by salting-out with ammonium
      sulfate. DEAE-cellulose column chromatography, gel filtration on Sephadex G-100,
      and hydroxylapatite column chromatography, HAF was glycoprotein which had a
      molecular weight of about 73,000. HAF was stable from pH 6 to 8 at 37 degrees C
      and up to 40 degrees C at pH 8.0 and the aggregation activity of HAF was maximum
      around pH 8 at 30 degrees C. The activity was not influenced by some saccharides,
      but it was inhibited by EDTA and EGTA: moreover HAF activity was restored by the
      addition of calcium ions. HAF aggregated hepatoma AH136B and COS-7 cells as well
      as hepatoma AH109A cells, but it was inert to other cancer cells and human
      erythrocytes. These properties proved that HAF is completely different from other
      aggregation factors for cancer cells so far reported.

PMID- 1369300
TI  - Arabinosylxylotriose mixedly esterified with acetic and ferulic acids from sugar
      cane bagasse.

PMID- 1369301
TI  - Growth of poliovirus using alginate entrapped-anchorage dependent Vero cells.
AB  - Obligatory anchorage dependant Vero cells were successfully grown in gelatinous
      like macrocarriers made of calcium alginate. Entrapped single cells were
      immobilized within the polymerized alginate matrix divide to form large spherical
      clumps of cells. A cell density of 17 x 10(6) cells/ml of alginate with over 95%
      viability was obtained after 14 days in spinner flasks. When subjected to
      poliovirus type I infection, spherical masses of Vero cells progressively showed
      extensive cytopathic effect but remained entrapped in the alginate matrix of the
      macrocarriers. Virus was released into a cellular debris free-like supernatant
      and reached a peak titer of 10(8.0) TCID50/ml after 72 hours.

PMID- 1369302
TI  - Immobilized antibody- and receptor-based biosensors.

PMID- 1369303
TI  - Properties of recombinant protein-containing inclusion bodies in Escherichia
      coli.

PMID- 1369304
TI  - Practical aspects of receptor affinity chromatography.

PMID- 1369305
TI  - Stability of recombinant plasmids for production of heterologous proteins in
      Escherichia coli.

PMID- 1369306
TI  - Long term and large-scale cultivation of human hepatoma Hep G2 cells in hollow
      fiber bioreactor. Cultivation of human hepatoma Hep G2 in hollow fiber
      bioreactor.
AB  - Long-term and large scale cultivation of an anchorage-dependent cell line using
      an industrial scale hollow fiber perfusion bioreactor is described. Hep G2 cells
      (a human hepatoma cell line) were cultivated in an Acusyst-P (Endotronic) with a
      total fiber surface area of 7.2 m2 6 x 1.2m2) to produce Hep G2 crude conditioned
      medium (CCM). Pretreatment of the cellulose acetate hollow fibers with collagen
      enhances the attachment of the anchorage-dependent cells. We have succeeded in
      growing the Hep G2 cells in an antibiotics- and serum-free IMDM medium,
      supplemented with 50 micrograms/ml of Hep G2 CCM protein at inoculation. The Hep
      G2 cells replicate and secrete CCM protein in quantities comparable to those
      produced in DMEM containing 10% fetal calf serum (FCS). The highest CCM protein
      productivity during the 80-day cultivation was 1.1 g/day with a total of 30 g of
      protein accumulated. Hep G2 CCM (20-40 micrograms protein/ml) was comparable to
      or even better than 10% FCS in supporting the growth of Molt-4 (a human T
      leukemia cell line) and FO (a mouse myeloma cell line) cells in vitro. The
      availability of this large amount of Hep G2 CCM will aid the further purification
      and characterization of growth factor(s) which could be used as serum
      substituents.

PMID- 1369307
TI  - Stimulation and inhibition of interferon-beta production of human diploid
      fibroblasts by foodstuffs.
AB  - We screened for foodstuffs affecting interferon-beta (IFN-beta) production of
      human foreskin diploid fibroblasts, in the presence of poly I.poly C,
      cycloheximide, and actinomycin D. alpha- and beta-caseins stimulated IFN-beta
      production dose-dependently, but kappa-casein inhibited it. Of the two chymosin
      fragments of kappa-casein, glycomacropeptide was an inhibitor but p-kappa-casein
      was not. beta-lactoglobulin stimulated IFN-beta production weakly, but
      lactoferrin inhibited it strongly. It was also shown that serum contained some
      factors inhibiting IFN-beta induction and stimulating its production.

PMID- 1369308
TI  - Kinetic investigation of penicillin G acylase from a mutant strain of Escherichia
      coli ATCC 11105 immobilized on oxirane-acrylic beads.
AB  - Highly purified penicillin G acylase from a mutant derivative of Escherichia coli
      ATCC 11105 was immobilized on oxirane-acrylic beads by covalent binding via
      oxirane groups. The highest specific activity, (322 U g-1 dry matrix at 40
      degrees C and at pH 8.0) was obtained by using an enzyme solution having 13.8 U
      mg-1 specific activity and 72.73 mg total protein. The efficiency of
      immobilization was 95.8%. Kinetic parameters of immobilized penicillin G acylase
      were determined at the same pH and temperature by a preparation having 8.1 mg
      bound protein. The Km value and substrate inhibition constant of the enzyme were
      found to be 11.36 mmol dm-3 and 680 mmol dm-3 penicillin G respectively.
      Phenylacetic acid and 6-aminopenicillanic acid were estimated as the competitive
      and non-competitive inhibitors of the enzyme and their inhibition constants were
      found to be 90 mmol dm-3 phenylacetic acid and 76.1 mmol dm-3 for 6
      aminopenicillanic acid. The activation energy of the hydrolytic reaction was
      calculated to be 7.75 kcal mol-1. The immobilized enzyme showed highest activity
      at pH 8.0 and at 55 degrees C. The enzyme was stable when incubated at 4 degrees
      C for one day at a pH range of 5.0 to 9.0. Thermal stability (over 30 min) was
      observed up to 40 degrees C but decreased at higher temperatures and was almost
      absent at 60 degrees C. A 95% conversion rate was observed at 28 degrees C and at
      40 degrees C with 60 and 30 min operation times respectively. Operational
      stability of the enzyme was improved further with dithiothreitol treatment.
      Activity loss was around 5% following 20 cycles of repeated use of the enzyme at
      40 degrees C. No significant loss of activity was observed at 28 degrees C when
      the enzyme was used for 20 cycles. 6-Aminopenicillanic acid in the reaction
      mixture was observed to be stable during conversion reactions which were carried
      out at both temperatures.

PMID- 1369309
TI  - Purification of restriction endonuclease from Acetobacter aceti IFO 3281 (AatII)
      and its properties.
AB  - The restriction endonuclease AatII was purified from cell-free extracts of
      Acetobacter aceti IFO 3281 by streptomycin treatment, ammonium sulfate
      fractionation, combined column chromatographies on DEAE-Toyopearl 650S, heparin
      Sepharose CL-6B and DEAE-Sepharose CL-6B and FPLC on Mono Q and on Superose 12
      (gel filtration). The purified enzyme was homogeneous on SDS-polyacrylamide gel
      disk electrophoresis. The relative molecular mass of the purified enzyme was
      190,000 daltons by gel filtration. The SDS-polyacrylamide gel disk
      electrophoresis gave the relative molecular mass of 47,500 daltons. These data
      indicated that the purified, native enzyme is a tetramer (190,000 daltons)
      composed of four 47,500-dalton subunits. The isoelectric point of the enzyme was
      6.0. The purified enzyme was intensely activated by manganese ion (50-fold
      increase or more when compared with magnesium ion). The enzyme worked best at 37
      degrees C and pH 8.5 in a reaction mixture (50 microliters) containing 1.0
      micrograms lambda DNA, 10 mM Tris-HCl, 7 mM 2-mercaptoethanol, 7 mM MnCl2 and 50
      mM NaCl. The enzyme recognizes the same palindromic hexanucleotide sequence 5'
      GACGTC-3', cuts between T and C and produces a 3'-tetranucleotide extension in
      the presence of MnCl2, as it does in the presence of MgCl2.

PMID- 1369310
TI  - Production of analytical quantities of recombinant proteins in Chinese hamster
      ovary cells using sodium butyrate to elevate gene expression.
AB  - Sodium butyrate was used to enhance expression levels and thereby facilitate the
      generation of analytical quantities of nine different tissue plasminogen
      activator (tPA) analogues expressed under the control of the cytomegalovirus
      immediate early (CMV IE) promoter by the Chinese hamster ovary (CHO) mammalian
      expression system. Production involved growth in roller bottles, using serum free
      or low serum media formulations, together with repetitive, sodium butyrate
      inductions. Average inductions in the presence of sodium butyrate ranged from 2
      to 9-fold relative to uninduced controls, using cell lines with no previous
      butyrate exposure. Retardation of growth rate by butyrate minimized the need to
      split cells during the production runs, extending longevity of roller bottles
      containing cells secreting at induced levels. SDS-PAGE analyses indicate a
      consistently high percentage of single-chain material. Measurements of specific
      activity and fibrinogen fragment enhancement for one of the analogues demonstrate
      that neither of these two critical parameters are affected by production in the
      presence of butyrate. Induction kinetic data and growth curves for the expression
      of sCD4 under control of the SV40 early promoter demonstrate that the benefits of
      butyrate can be realized with different promoters and heterologous genes, and are
      additive when used in conjunction with an amplified cell line constitutively
      expressing at elevated levels. This work demonstrates the practical application
      of sodium butyrate in the production of analytical quantities of protein from the
      CHO expression system, and suggests a role for sodium butyrate in commercial
      scale processes as well.

PMID- 1369311
TI  - Purification and properties of restriction endonuclease from Deleya marina IAM
      14114, a marine bacterium (DmaI).
AB  - A restriction endonuclease, designated as DmaI, was purified from cell-free
      extracts of Deleya marina IAM 14114 by streptomycin treatment, ammonium sulfate
      fractionation and two steps of chromatographies on heparin-Sepharose CL-6B and
      Mono Q (HR 5/5, FPLC). The purified enzyme was homogeneous on SDS-polyacrylamide
      gel disk electrophoresis and a ligation-recutting test. The relative molecular
      mass measurements of the purified enzyme gave 28,000 daltons by SDS
      polyacrylamide gel disk electrophoresis and 56,000 daltons by gel filtration.
      These data indicated that the purified enzyme (56,000 daltons) has a dimeric
      structure composed of two 28,000-dalton subunits. The isoelectric point was 5.5.
      The purified enzyme worked best at 37 degrees C in a reaction mixture (50
      microliters) containing 1.0 micrograms lambda DNA, 10 mM Tris-HCl, 7 mM 2
      mercaptoethanol, 7 mM MgCl2 and 100 mM NaCl (pH 7.5). The enzyme was stable up to
      55 degrees C and between pH 7.0 and 9.0. The purified enzyme recognizes the
      palindromic hexanucleotide DNA sequence 5'-CAGCTG-3', cuts between G and C and
      produces a flush end (isoschizomer of PvuII).

PMID- 1369312
TI  - New pyrrolobenzodiazepine antibiotics, RK-1441A and B. I. Biological properties.
AB  - Streptomyces griseus and bacteriophage B were used for an assay system detecting
      anti-bacteriophage antibiotics. Streptomyces sp. RK-1441 was found to produce
      antibacteriophage antibiotics, RK-1441A and B, which are
      pyrrolo[1,4]benzodiazepine group antibiotics related to neothramycin. Both RK
      1441A and B had antibacteriophage activity. The former showed antimicrobial
      activity on a hypersensitive strain of E. coli for antitumor antibiotics, but the
      later did not show the activity. Restriction enzyme assay suggested that RK-1441A
      formed adducts with guanine residues in DNA strands. RK-1441B was not active in
      vitro, but it might be converted to the active form in host organisms.

PMID- 1369313
TI  - Purification and properties of a new restriction endonuclease, MxaI, from
      Myxococcus xanthus F18E.

PMID- 1369314
TI  - Substrate specificity of alpha-galactosidase from Aspergillus niger 5-16.
AB  - This paper describes the specificity of Aspergillus niger 5-16 alpha
      galactosidase toward various oligosaccharides having terminal galactose or stub
      galactose or both on the oligosaccharide. The galactosidase rapidly hydrolyzed p
      nitrophenyl-alpha-D-galactopyranoside, but hardly liberated galactose from
      melibiose, manninotriose, 6(3)-alpha-D-galactosylmannotriose, etc. On the other
      hand, the enzyme tore off the stub galactoses attached to the inner mannoses of
      the main-chain of galactomannooligosaccharides, but not the terminal galactoses
      attached to the non-reducing-end mannoses of the main-chain. Thus, the substrate
      specificity of A. niger 5-16 alpha-galactosidase is quite different from that of
      Mortierella vinacea alpha-galactosidase.

PMID- 1369315
TI  - Interactions between novel tumor necrosis factor-alpha mutants and receptors on
      tumor and normal cells.
AB  - We prepared several TNF mutants by protein engineering techniques and compared
      their biological properties with those of the wild-type TNF. The mutant that
      lacked 7 N-terminal amino acids had higher cytotoxicity and higher binding
      activity to receptors on tumor cells. In contrast, the mutagenesis of Arg32 or
      Ala84, in combination with the deletion of 7 N-terminal amino acids, eliminated
      the cytotoxicity and the receptor binding. These mutants also lacked acute lethal
      toxicity in normal mice. Therefore, we concluded that the N-terminus, Arg32 and
      Ala84 of TNF might be concerned with binding to the TNF receptor. It was also
      suggested that the receptor molecules on tumor cells bound to the same or
      neighboring sites on TNF molecules as normal cell receptors.

PMID- 1369316
TI  - Metal-affinity separations: a new dimension in protein processing.
AB  - Rapid growth in the preparative and high-resolution analytical applications of
      metal-affinity chromatography demonstrate the appeal of metal recognition as a
      basis for protein separations. Stable, inexpensive chelated metals effectively
      mimic biospecific interactions, providing selective ligands for protein binding.
      This article reviews recent progress in understanding the mechanisms of metal
      protein recognition that underlie metal-affinity separations. Also discussed are
      schemes for integrating metal-affinity purifications into the expression and
      bioprocessing of recombinant proteins. Promising future developments include new
      metal-affinity processes for analytical and preparative-scale separations and a
      range of techniques for enhancing the selectivity of metal-affinity separations.

PMID- 1369317
TI  - Renaturation, purification and characterization of recombinant Fab-fragments
      produced in Escherichia coli.
AB  - Cytoplasmatic expression of murine antibody chains in Escherichia coli results in
      the formation of insoluble and inactive protein aggregates (inclusion bodies). By
      systematic variation of the parameters influencing the folding, formation of
      disulfide bonds and association of the constituent polypeptide chains, we have
      designed a renaturation procedure allowing the production of microbially
      expressed Fab-fragments at yields up to 40 percent of the total amount of
      recombinant protein. The strategy of optimization is generally applicable for
      disulfide containing proteins produced as inclusion bodies in bacteria. The
      purified recombinant antibody fragments obtained are identical with the native
      murine Fab in all functional and physicochemical parameters tested.

PMID- 1369318
TI  - Isolation of mutants with improved production of cAMP from Microbacterium sp. no.
      205 (ATCC 21376).
AB  - Mutants were isolated from Microbacterium sp. no. 205 (ATCC 21376) producing 13
      30 mM cyclic adenosine 3',5'-monophosphate (cAMP) by salvage biosynthesis,
      through sequential improvements of the bacterium for the purpose of improving
      cAMP production. The mutants produced 50-75 mM cAMP on 100 mM inosine 5'
      monophosphate as a precursor. Mutants resistant to the inhibition of growth by
      cAMP at high concentrations were isolated; the resistance was one of four
      characteristics effective for improved production of cAMP.

PMID- 1369319
TI  - Endothelial cell-selective materials for tissue engineering in the vascular graft
      via a new receptor.
AB  - We have found a novel adhesion receptor on the human endothelial cell for the
      peptide sequence Arg-Glu-Asp-Val (REDV), which is present in the III-CS domain of
      human plasma fibronectin, with a dissociation constant of 2.2 x 10(-6) M and 5.8
      x 10(6) sites/cell. When a synthetic peptide containing this sequence was
      immobilized on otherwise cell nonadhesive substrates, endothelial cells attached
      and spread but fibroblasts, vascular smooth muscle cells, and platelets did not.
      Endothelial monolayers on REDV were nonthrombogenic: endothelial cells attached
      and spread upon other receptor-binding domains of fibronectin and laminin, but
      with lesser degrees of specificity or with a loss of nonthrombogenicity. This
      approach may provide a basis for a tissue engineered vascular graft where
      endothelial cell attachment is desired, but not the attachment of other blood
      vessel wall cells and blood platelets.

PMID- 1369320
TI  - Amplification of three threonine biosynthesis genes in Corynebacterium glutamicum
      and its influence on carbon flux in different strains.
AB  - The hom-thrB operon (homoserine dehydrogenase/homoserine kinase) and the thrC
      gene (threonine synthase) of Corynebacterium glutamicum ATCC 13,032 and the
      homFBR (homoserine dehydrogenase resistant to feedback inhibition by threonine)
      alone as well as homFBR-thrB operon of C. glutamicum DM 368-3 were cloned
      separately and in combination in the Escherichia coli/C. glutamicum shuttle
      vector pEK0 and introduced into different corynebacterial strains. All
      recombinant strains showed 8- to 20-fold higher specific activities of homoserine
      dehydrogenase, homoserine kinase, and/or threonine synthase compared to the
      respective host. In wild-type C. glutamicum, amplification of the threonine genes
      did not result in secretion of threonine. In the lysine producer C. glutamicum DG
      52-5 and in the lysine-plus-threonine producer C. glutamicum DM 368-3
      overexpression of hom-thrB resulted in a notable shift of carbon flux from lysine
      to threonine whereas cloning of homFBR-thrB as well as of homFBR in C. glutamicum
      DM 368-3 led to a complete shift towards threonine or towards threonine and its
      precursor homoserine, respectively. Overexpression of thrC alone or in
      combination with that of homFBR and thrB had no effect on threonine or lysine
      formation in all recombinant strains tested.

PMID- 1369321
TI  - Poliovirus RNA recombination.
AB  - We are developing an in vitro system for poliovirus RNA recombination. In this
      system, two mutant RNAs are replicated with poliovirus RNA-dependent RNA
      polymerase. Recombination will produce RNAs containing neither mutation and will
      be the only progeny RNAs that are infectious. We will use this system to
      determine what proteins and reaction conditions are required for recombination
      and to study the details of the mechanism of recombination.

PMID- 1369322
TI  - A molecular model for illegitimate recombination in Bacillus subtilis.
AB  - The recombinant DNA junctions at which pUB110 and Bacillus subtilis chromosomal
      DNA were joined to form the plasmid pKBT1 were cloned and sequenced. From the
      sequencing data we conclude that the pUB110 sequence is intact in the pair of
      cloned pKBT1 fragments and pTL12 sequences are not present. A molecular model for
      the formation of pKBT1 based on structural motifs characteristic of the joint
      sites is presented.

PMID- 1369323
TI  - Identification of sites of pre-MRNA/spliceosome association.
AB  - RNase H and synthetic DNA oligonucleotides were used to analyze the
      ribonucleoprotein (RNP) structure of the yeast spliceosome and to assay the pre
      mRNA sequence requirements for step 1 of splicing. The data suggest that tight,
      stable contacts between the pre-mRNA and the spliceosome may be limited to the 5'
      splice site and branch point regions of the intron. A 30 nucleotide segment 3' of
      the branch point was found to be necessary for spliceosome maturation and
      essential for step 1 of splicing. Somewhat surprisingly, the 3' splice site was
      sensitive to nuclease digestion and completely dispensable for step 1 of
      splicing.

PMID- 1369324
TI  - Primary structure of a nuclease (nuclease PA3) from a Penicillium sp.
AB  - The complete primary structure of a nuclease from a Penicillium sp. [nuclease PA3
      (Kazama et al., Chem. Pharm. Bull., 38, 3081 (1990)] was determined. The
      sequencing was done by analysis of the peptides generated by digestion of reduced
      and carboxymethylated nuclease PA3 (RCM nuclease PA3) with lysylendopeptidase,
      and by digestion with staphylococcal V8 protease or chemical cleavage with BrCN.
      It consisted of 270 amino acid residues and carbohydrate moieties attached to the
      92nd, 138th, 184th, and 197th asparagine residues. The molecular weight of the
      protein moiety deduced from the sequence was 29,211. It contains four half
      cystine residues. The amino acid sequence was identical with that of P1 nuclease
      from Penicillium citrinum [K. Maekawa, S. Tsunasawa, G. Dibo, and F. Sakiyama,
      Abstracts of Papers, the 62nd Meeting of the Biochemical Society of Japan,
      Seikagaku, 61, 1013 (1989)] except that the 190th Thr residue was Ile in P1
      nuclease.

PMID- 1369325
TI  - Constitutive high-level production of human lymphotoxin by CHO-K1 cells
      transformed with the human lymphotoxin gene controlled by a human beta-actin
      promoter.
AB  - To achieve high-level production of human lymphotoxin (hLT), a plasmid (p beta LT
      ldhfr) containing the hLT genomic DNA, a mouse dihydrofolate reductase (DHFR)
      cDNA, and a bacterial Ecogpt gene was cotransfected with a plasmid (p beta LTML)
      encoding only the hLT genomic DNA into Chinese hamster ovary (CHO-K1) cells at a
      1:7 molar ratio. Subsequently one of the Ecogpt-positive clones (clone A31) was
      grown in stepwise increasing concentrations of methotrexate (MTX). A large amount
      of the hLT was secreted by cells resistant to increased levels of MTX as a result
      of coamplification of the DHFR cDNA and the hLT gene. A cell clone (clone M-1)
      resistant to up to 500 nM MTX constitutively expressed the hLT at a concentration
      of 80 micrograms per ml at an elevated level for about 2 months. The hLT was
      produced in glycosylated form the molecular mass of which was 23,000 daltons and
      the mRNA was normally spliced, so the protein molecules were probably
      homogeneous.

PMID- 1369326
TI  - Structural features of the sulphated polysaccharide from a green seaweed,
      Cladophora socialis.
AB  - A sulphated heteropolysaccharide, [alpha]27D + 59.9 degrees, has been isolated
      from a green seaweed, Cladophora socialis, by extraction with dilute acid and
      purified by fractional precipitation. The polymer is composed of galactose
      (58.3%), arabinose (31.8%), xylose (10.6%) and sulphate (16.9%). The results of
      methylation analysis, periodate oxidation and partial acid hydrolysis studies
      indicate that the polymer is a branched one and is composed of 1,3-linked
      galactose and 1,4-linked arabinose units. Xylose is present at the non-reducing
      end position of the branches. Both arabinose and galactose carry branches.
      Desulphation and subsequent analysis of the polymer show that some of the
      arabinose units carry sulphate groups at C-3 and some of the galactose units
      carry the sulphate groups at C-4 and some at C-4 and C-6 as well.

PMID- 1369327
TI  - Tailoring and targeting fibroblast growth factors.

PMID- 1369328
TI  - Viral contamination of therapeutic proteins: a challenge for downstream
      processing.

PMID- 1369329
TI  - Transposition and transduction of plasmid DNA in Streptomyces spp.
AB  - To expand the application of molecular genetics to many different streptomycete
      species, we have been developing two potentially widely applicable methodologies:
      transposon mutagenesis and plasmid transduction. We constructed three transposons
      from the Streptomyces lividans insertion sequence IS493. Tn5096 and Tn5097
      contain an apramycin resistance gene inserted in different orientations between
      the two open reading frames of IS493. These transposons transpose from different
      plasmids into many different sites in the Streptomyces griseofuscus chromosome
      and into its resident linear plasmids. Tn5099 contains a promoterless xylE gene
      and a hygromycin-resistance gene inserted in IS493 close to one end. Tn5099
      transposes in S. griseofuscus giving operon fusions in some cases that drive
      expression of the xylE gene product, catechol deoxygenase, giving yellow colonies
      in the presence of catechol. We have also developed plasmid vectors that can be
      transduced into many streptomycete species by bacteriophage FP43. We describe the
      characterization of FP43 and mapping of several bacteriophage functions. The
      region of cloned FP43 DNA essential for plasmid transduction includes the origin
      for headful packaging.

PMID- 1369330
TI  - High-resolution particle size analysis in biotechnology process control.
AB  - Many industrially important proteins can now be expressed intracellularly as
      insoluble protein inclusion bodies. In production, large-scale centrifugation is
      commonly used to separate and recover the inclusion bodies. Recovery efficiency
      depends critically on the centrifuge feed rate, which must be optimized to
      minimize production costs. We have used a disc centrifuge photosedimentometer to
      make high-resolution measurements of the particle size distribution (PSD) of the
      supernatant during the production of porcine somatotropin (pST) inclusion bodies.
      These measurements readily monitor the breakthrough of inclusion bodies into the
      supernatant and allow the centrifugation operation to be optimized.

PMID- 1369331
TI  - DNA recovery and direct detection of Tn5 sequences from soil.
AB  - Specific Tn5 sequences inserted in the genome of Enterobacter agglomerans were
      detected in EcoRI digested DNA directly recovered from soil 70 d after its
      inoculation with the bacteria, when these were no longer culturable on agar
      medium. A new method of DNA extraction from soil was used. No amplification of
      DNA sequences by PCR was needed.

PMID- 1369332
TI  - Growth of transformed C-127 cell in bioreactors for large-scale T-PA production.

PMID- 1369333
TI  - Design and use of synthetic oligonucleotide probes in the cloning of delta
      endotoxin genes from Bacillus thuringiensis.
AB  - A detailed protocol is described for the design and use of synthetic
      oligonucleotide probes for screening DNA libraries from Bacillus thuringiensis
      var. kurstaki (strain HD191) for copies of the gene (tox) encoding the
      insecticidal delta-endotoxin. Two homologous tox genes were identified in this
      organism; one of these was located on a 75-kb plasmid and the other on a second
      large plasmid or the bacterial chromosome. A tox gene was isolated as a 6.5-kb
      HindIII fragment of B. thuringiensis plasmid DNA.

PMID- 1369334
TI  - Expression of recombinant calf prochymosin in mammalian cell culture.
AB  - The calf preprochymosin cDNA was cloned into an extrachromosomal mammalian cell
      expression vector containing Epstein-Barr virus sequences using polymerase chain
      reaction. Transfection of HeLa cells yielded Hygromycin B resistant cell clones,
      expressing immunoreactive prochymosin, which was quantitatively secreted into the
      culture medium. Based on Western blotting we estimated that selected cell clones
      produced about 10-20 mg prochymosin per liter in 20 h. The biological activity of
      the secreted chymosin was confirmed by milk clotting assay.

PMID- 1369336
TI  - Selective removal of ammonia from animal cell culture broth.
AB  - Serum-free perfusion cultures of hybridoma TO-405 cells were carried out in
      spinner flasks coupled with zeolite A-3 packed beads. Ammonia was selectively
      removed from the culture broth by passing cell free permeate from ceramic cross
      flow filtration, through the zeolite packed bed. Ammonia concentration in the
      culture broth was effectively maintained between 1 to 4 mmol/l which was below
      the inhibitory concentration for cell growth. Maximum cell density levels of
      10(7) cells/ml as well as improved percentage cell viability higher than in serum
      supplemented cultures were feasible in this system. The possible effects of shear
      stress, generated by variation of the flow rates of the broth through the ceramic
      filter module, on the growth of the hybridoma cells were investigated.
      Backwashing, by reversing the direction of the permeate, was found necessary to
      prolong the life of the filter. Variation of the flow rates of the broth through
      the ceramic module between 0.29 m/s to 0.59 m/s did not cause immediate cell
      damage but growth was repressed at the higher flow rate. This study also showed
      that glutamine appears to be one of the factors limiting the growth of the
      hybridoma cells.

PMID- 1369335
TI  - Establishment and characterization of monoclonal antibodies against Chuzan virus
      K-47.
AB  - We established sixteen mouse monoclonal antibodies reactive to Chuzan virus K-47
      strain using P3-X63-Ag8-U1 cells as fusion partner cells. Among them, CG53/2/4
      recognized a 100K structural protein of the virus. The 100K antigen lost it's
      antigenicity for CG53/2/4 after mild periodate oxidation treatment, suggesting
      that the 100K viral antigen is a glycoprotein. In addition, CG53/2/4 neutralized
      the viral infectivity. This indicates that the 100K glycoprotein is essential for
      the infection of the virus. The other monoclonal antibodies reacted with a 41K
      antigen of the virus. Especially CG1/1 showed the highest reactivity to the
      virus. Forward step sandwich assay using CG1/1 and biotinylated CG53/2/4 could
      detect the virus at 10TCID50/ml. Therefore, these monoclonal antibodies can
      eventually predict the virus infection to the animals before their sideration.

PMID- 1369337
TI  - The Mutator transposable element family of maize.

PMID- 1369338
TI  - Functions of intracellular protein degradation in yeast.
AB  - Diverse vacuolar and nonvacuolar pathways of protein degradation have been
      described in yeast. In several cases, much is known about the proteases involved,
      but most of these studies utilized nonphysiological model substrates. On the
      other hand, many regulatory proteins, such as those involved in cell cycle
      control, cell type determination, and the regulation of metabolite fluxes through
      biosynthetic pathways, have been shown to be rapidly and selectively destroyed in
      vivo, either constitutively or in response to specific regulatory signals.
      Precisely what molecular features of this class of proteins target them for
      degradation is largely unknown; this question is an area of intense current
      interest. A connection has been made between a particular proteolytic mechanism
      and a specific naturally short-lived protein in only a handful of examples. It is
      in this regard that the powerful molecular and genetic techniques available in
      yeast will probably have their greatest impact in the near future. The promise of
      this type of approach is already becoming apparent with the molecular genetic
      analysis of the yeast ubiquitin system. Although this work began less than ten
      years ago, the genes encoding at least 22 proteins involved in ubiquitin
      dependent processes have already been isolated, and questions of their
      physiological and mechanistic function are being answered at an ever quickening
      pace.

PMID- 1369339
TI  - Protein phosphorylation and the regulation of cellular processes by the
      homologous two-component regulatory systems of bacteria.

PMID- 1369340
TI  - Positive identification of a lambda gt11 clone containing a region of fungal
      phytase gene by immunoprobe and sequence verification.
AB  - As the initial step in a project to provide a more cost-effective source of the
      phytase enzyme, this paper reports on the use of a polyclonal antibody raised to
      phytase purified from an isolate of Aspergillus niger (A. ficuum) to screen an A.
      niger lambda gt11 expression library and the use of amino acid sequencing to
      identify a clone containing part of the fungal phytase gene. The described use of
      amino acid sequence fragments to verify the cloning of a gene has potential
      applications in other cloning projects.

PMID- 1369341
TI  - Expression of chimeric ras protein with OmpF signal peptide in Escherichia coli:
      localization of OmpF fusion protein in the inner membrane.
AB  - The ras gene was fused with the DNA sequence of OmpF signal peptide or with the
      DNA sequence of OmpF signal peptide plus the amino terminal portion of the OmpF
      gene. They were placed in plasmids together with the bacteriophage lambda PL
      promoter. These plasmids were introduced into Escherichia coli strain K-12 and
      the OmpF signal peptide fusion proteins were expressed. These fusion proteins
      were identified as 29.0 and 30.0 kDa proteins. However, processed products of
      these proteins were not found in the extract. The fusion proteins were localized
      mostly in the cytoplasm and the inner membrane, but none of them was secreted
      into the periplasmic space. On the other hand, the ras protein alone was found in
      the cytoplasm and not in the inner membrane. Viable counts of E. coli harbouring
      these plasmids decreased when these fused proteins were induced. Induction of the
      ras protein alone did not harm cells. These observations suggest that insertion
      of the heterologous proteins into the inner membrane may cause the bactericidal
      effect.

PMID- 1369342
TI  - Retroelement particles as purification, presentation and targeting vehicles.
AB  - The manipulation of retrotransposon and retroviral particles to carry
      biologically active molecules is becoming feasible. In addition, recent
      experiments suggest that it may be possible to target these engineered particles
      to specific cell types. This has implications for gene therapy, biological drug
      delivery and vaccine design.

PMID- 1369343
TI  - Micro-targeting: high efficiency gene transfer using a novel approach for the
      acceleration of micro-projectiles.
AB  - We have constructed a novel micro-projectile accelerating system for efficient
      gene transfer into cells in situ that avoids binding DNA to micro-projectiles and
      keeps the DNA in solution. Further, instead of a macro-projectile (or the
      equivalent), it accelerates the particles in a Bernoulli air stream. The micro
      targeting approach directs highly dispersed particles to sites with diameters as
      little as 0.15 mm, allowing precise aiming to restricted tissues. The system is
      physically flexible and should therefore be adaptable to different tissues and
      species. Transient expression of the Escherichia coli beta-glucuronidase gene in
      immature wheat embryo scutella was obtained at a frequency of up to 3% of the
      treated cells in the surface layer. In tobacco SR1, we achieved many transgenic
      plants, and the efficiency of stable transformation with the neomycin
      phosphotransferase (NPTII) gene was approximately 10(-3) per exposed cell.

PMID- 1369344
TI  - Encapsulated cells target diabetes & Parkinson's.

PMID- 1369345
TI  - Altered reactivity of immunoglobulin produced by human-human hybridoma cells
      transfected by pSV2-neo gene.
AB  - The HB4C5 and HF10B4 cell lines are human-human hybridomas producing human IgM
      monoclonal antibodies (MAbs) reactive to porcine carboxypeptidase A (CPase), but
      not to double stranded DNA (ds DNA). We obtained G418-resistant HB4C5 and HF10B4
      cells by an introduction of pSV2-neo DNA. Almost all of the G418-resistant clones
      produced MAbs reactive to not only the CPase but the ds DNA. The results of the
      inhibition ELISA suggested that the cross-reactivity of the antibodies from G418
      resistant clones to CPase and ds DNA was responsible for the alteration on their
      antigen specificity. HB4C5 and HF10B4 cells and their G418-resistant clones
      produced antibodies having glycosylated lambda chain. The antibodies produced by
      tunicamycin-treated G418-resistant subclones of HB4C5 and HF10B4 lost the ability
      to bind to ds DNA, but retained the ability to bind to CPase. These results
      suggest that an introduction of pSV2-neo DNA into these hybridomas alters the
      specificities of their MAbs, and that the alteration to antigen binding
      specificities of their MAbs may be associated with glycosylation of the MAbs by
      these hybridomas.

PMID- 1369346
TI  - Designing peptide and protein ligands for biological receptors.
AB  - A clearer understanding of structure-function relationships of protein hormone
      receptor systems is emerging from the increased use of molecular biology
      approaches. On the other hand, the introduction of rationally designed
      conformation constraints into peptide hormones and neurotransmitters is leading
      to the development of highly receptor-selective ligands that allow further
      investigations into the topographic modulation of their bioactivities and
      rational design principles for peptide antagonists.

PMID- 1369347
TI  - Genetic transformation of Aureobasidium pullulans.
AB  - Aureobasidium pullulans strain Y117 was transformed to hygromycin resistance
      using plasmid pDH33, which contains the bacterial hygromycin B phosphotransferase
      gene (hph) fused to promoter elements of the Aspergillus niger glucoamylase gene
      (glaA). Southern hybridizations of transformants revealed multiple, integrated
      copies of the vector. The glaA promoter was not induced by starch in A. pullulans
      as it is in A. niger; however, the transcriptional start points were the same in
      both species.

PMID- 1369349
TI  - Receptor-based assays.
AB  - Receptor-based assays have benefitted from the newest advances in biotechnology
      and electronics in three main ways: genetically engineered cells expressing
      single receptor subtypes have been developed for many natural and synthetic
      ligands; assays have been designed which take advantage of a variety of signals
      triggered in cells by binding, or inhibition of binding, of ligands to surface
      bound receptors; and radiolabelled ligand assays have been considerably improved
      and simplified by novel electronic devices.

PMID- 1369348
TI  - Characterization of endosteal osteoblasts isolated from human maxilla and
      mandible: an experimental system for biocompatibility tests.
AB  - Fragments of cancellous and cortical bone from human maxilla and mandible were
      cultured by the explant technique. Cells isolated by trypsinization of primary
      cultures were characterized as osteoblasts on the basis of intracellular alkaline
      phosphatase activity, the constituents of the extracellular matrix, and response
      to human parathormone (PTH). In culture, the osteoblasts often gave rise to
      superposed clumps of large cells whose cytoplasm contained endoplasmic reticulum,
      numerous mitochondria, vacuoles, and a dense network of intermediate filaments,
      often at the level of the plasma membrane. In the presence of vitamin C and 1,25
      dihydroxyvitamin D3, the osteoblasts produced an extracellular matrix composed of
      collagen type I and various non-collagenous proteins, including osteocalcin.
      Biochemical test results were comparable to those reported for osteoblasts of
      other origins (rat calvaria, human iliac crest), and namely elevated
      intracellular alkaline phosphatase activity and cAMP accumulation in response to
      stimulation by human PTH (1-34). Osteoblasts isolated in this manner were
      cultured in the presence of pure titanium disks to determine the effects of
      exposure to this metal. Electron microscopy revealed few significant differences
      in cell growth and specific enzyme activity compared to control osteoblasts grown
      on plastic dishes, reflecting the excellent biologic and biochemical relationship
      between the osteoblasts and pure titanium. This experimental system thus appears
      suitable for biocompatibility studies, and in particular, evaluation of dental
      implants.

PMID- 1369350
TI  - Biosensors for process control.
AB  - Biosensors have been extensively studied during the last 20 years, and a myriad
      of laboratory biosensors have been developed. Improvements are required in
      biosensor design and performance before they become widely accepted in industrial
      process monitoring. However, as the biotechnology industry expands, biosensors
      may become more acceptable because, despite their limitations, they are the only
      devices capable of delivering the information required.

PMID- 1369351
TI  - Technological advances in poultry vaccines.
AB  - The work described in this paper represents an extended program utilizing both
      traditional and novel technologies to develop a range of poultry vaccines which
      target current or emerging opportunities in domestic and international
      marketplaces. The successes with the traditional products to date have been
      gratifying and the advent of a series of recombinant vaccines over the next few
      years holds promise for the generation of a range of novel immunobiologicals.

PMID- 1369352
TI  - Poliovirus antigen chimeras.
AB  - Poliovirus, the aetiological agent of paralytic poliomyelitis, is arguably the
      best characterized of all animal viruses. Using recombinant-DNA technology, this
      information, together with the availability of infectious cDNA clones of the
      notably safe and efficacious live attenuated Sabin 1 vaccine strains of
      poliovirus, has enabled the creation of hybrid viruses (chimeras) possessing
      novel antigenicity. The potential applications of these 'epitope-presentation
      systems' include their use as immunogens, as antigens for serodiagnosis, and as
      vaccines.

PMID- 1369353
TI  - Enhanced secretion of human nerve growth factor from Saccharomyces cerevisiae
      using an advanced delta-integration system.
AB  - We have designed an advanced delta-integration system (integration of genes into
      the delta-sequence of yeast retrotransposon Ty) and used it for secretion of
      human nerve growth factor (hNGF) from Saccharomyces cerevisiae. The expression
      and secretion of hNGF was directed by the PGK promoter and MF alpha 1 prepro
      signal. Using two selectable markers (URA3 and leu2-d), haploid yeast strains
      were constructed with approximately 20 copies of a delta-integrated hNGF
      expression cassette on four chromosomes. The strain secreted hNGF at levels 3-4
      fold higher than a 2 micron-based plasmid. Northern and Western analyses revealed
      that the oversecretion was caused by an increased amount of mRNA. We also
      detected an unusual processing of the MF alpha 1 prepro-hNGF fusion protein that
      required the pep4 mutation. Application of this system for industrial purposes is
      discussed.

PMID- 1369354
TI  - Protein stabilization by engineered metal chelation.
AB  - A ligand can shift a protein's folding/unfolding equilibrium by binding with
      higher affinity to the native state. A metal-chelating site consisting of two
      histidines separated by three residues (His-X3-His) engineered into an alpha
      helix provides a general and easily-implemented means for protein stabilization
      by this mechanism. We have tested this approach with the iso-1-cytochrome c of
      Saccharomyces cerevisiae substituted with histidine at positions 4 and 8 in its N
      terminal alpha-helix. One mM Cu(II) complexed to iminodiacetate stabilizes the
      cytochrome c variant by ca. 1 kcal/mol, as determined by guanidinium chloride
      induced unfolding. The protein's folding/unfolding equilibrium is shifted by a
      free energy equal to that calculated from the metal ion's preferential binding to
      the native protein. Given the ubiquity of surface alpha-helices and the
      additional possibility of inserting di-histidine chelating sites into turns and
      beta-structures, we conclude that this is a useful method for protein
      stabilization.

PMID- 1369355
TI  - Immunomodulation: suppression, enhancement and autoimmunity.
AB  - Recent reports highlight new approaches to immunointervention (suppression or
      enhancement) based on the known roles of lymphocyte populations, cytokines and
      their receptors, and adhesion molecules in immune responses. Considerable
      interest over the past year has focused on immunophilins (cyclophilin and the
      FK506-binding protein) which appear to play key roles in signal transduction
      within activated T cells and provide a molecular basis for new advances in
      immunosuppressive drug therapy.

PMID- 1369356
TI  - Growth factors and receptors in cancer.
AB  - There have been a number of recent developments in mechanisms of action of growth
      factors and their receptors with particular relevance to cancer. The tyrosine
      kinase receptor family, in particular, has been shown to be important in tumour
      growth. These receptors are the products of oncogenes, or can interact with other
      oncogene pathways. Thus, antibodies to either the receptor or its ligand can be
      used as therapeutic agents. Peptide analogues of ligands that can block receptor
      activation are also potential therapeutic agents.

PMID- 1369357
TI  - Receptors for neurotransmitters and related substances.
AB  - Advances in techniques for cloning neurotransmitter receptors have revealed new
      targets for selective drug design. Cell systems for more efficient expression of
      cloned receptor genes have also been developed. Knowledge of the nature of ligand
      binding sites is now becoming available and this should aid in the design of
      better drugs with fewer side effects.

PMID- 1369358
TI  - A restriction endonuclease (DpaI) from Deleya pacifica IAM 14115, a marine
      bacterium, an isoschizomer of ScaI.

PMID- 1369360
TI  - Gene expression using DNA viral vectors.

PMID- 1369361
TI  - Plant expression systems.

PMID- 1369359
TI  - Molecular cloning and expression of the VP1 gene of foot-and-mouth disease virus
      C1 in E. coli: effect on bacterial cell viability.
AB  - The VP1 gene of foot-and-mouth disease virus (serotype C1) has been cloned in
      Escherichia coli Clts cells, under the control of the bacteriophage lambda pL
      promoter. The expressed VP1 protein was complete and non-fused, and its molecular
      weight was indistinguishable from that of the VP1 obtained from virions. Cells
      harbouring the recombinant vectors exhibited symptoms of plasmid instability and
      toxicity and died in a few weeks even when never exposed to inducing conditions.
      A new plasmid clone in which a segment of the VP1 gene was fused with contiguous
      genes of the viral genome was very stable. The expressed partial VP1 protein
      contains the two major immunogenic domains of the virion. This system can be used
      as a tool to design an immunogenic VP1, and to explore possible synthetic
      vaccines against foot-and-mouth disease.

PMID- 1369362
TI  - Identification of polymerized-albumin receptor domain in the pre-S2 region of
      hepatitis B virus surface antigen M protein.
AB  - The pre-S2-coding region in the hepatitis B virus surface antigen M (P31; pre-S2
      + S) protein gene was modified to identify a polymerized-albumin receptor (PAR)
      domain by deleting restriction fragments or performing site-directed mutagenesis.
      The modified M protein genes (M-P31x; x = d, e, f, h and i) were cloned into the
      yeast generalized-expression vector pGLD 906-1 and expressed in Saccharomyces
      cerevisiae under the control of yeast glyceraldehyde-3-phosphate dehydrogenase
      gene promoter. The PAR activities of these gene products suggested that the PAR
      domain is located in the hydrophilic and highly conserved domain in the pre-S2
      region (around Leu12 approximately Tyr21). Antibodies specific for a pre-S2
      peptide (Phe8 approximately Pro34, subtype adr), which covers the PAR domain,
      were purified from sera of rabbits immunized with yeast-derived M protein
      particles having a natural PAR domain. Immune electron microscopy showed that the
      purified antibodies could aggregate HBV particles. Therefore, it was speculated
      that the PAR domain overlapped with the dominant virus-neutralizing and virus
      protecting epitopes.

PMID- 1369363
TI  - Formation of bioerodible polymeric microspheres and microparticles by rapid
      expansion of supercritical solutions.
AB  - Polyhydroxy acids [poly(L-lactic acid) (L-PLA), poly(D,L-lactic acid) (DL-PLA),
      and poly-(glycolic acid) (PGA)], biocompatible and bioerodible polymers that are
      being investigated for controlled delivery of pharmaceuticals and are approved by
      the Food and Drug Administration for in vivo sutures and bone repair implants,
      have been dissolved in supercritical CO2 and precipitated by rapid expansion of
      the resulting supercritical solutions (RESS). The formation of these
      microparticles and microspheres is a first step toward the goal of producing, in
      a single processing step, drug-loaded polymeric microspheres for use in
      controlled release applications. Nucleation of poly(L-lactic acid) from CO2 and
      CO2-acetone mixtures produced microparticles and microspheres ranging from 4 to
      25 microns. Microspheres (2-20 microns) were also obtained with
      chlorotrifluoromethane as solvent. Commercial L-PLA precipitated after extraction
      of low molecular weight oligomers showed degradation kinetics similar to that of
      the starting material. The precipitation of DL-PLA from CO2 produced irregular
      sized particles (10-20 microns). PGA, a polymer insoluble in most organic
      solvents, was found to be soluble in supercritical CO2. Nucleation of PGA from
      CO2 produced both regular-sized particles and needles of 10-40-microns length.
      The total solubility of commercial L-PLA in supercritical CO2 at 250 bar and 55
      degrees C decreased from 0.14 wt % to less than 0.05 wt % and then leveled off as
      the cumulative flow of CO2 per unit mass of L-PLA loaded in the extractor
      increased beyond 20 standard L of CO2/g of L-PLA. Use of acetone (1 wt %) as a
      cosolvent increased L-PLA solubility by approximately 500%.

PMID- 1369364
TI  - Maximizing the expression of a recombinant gene in Escherichia coli by
      manipulation of induction time using lactose as inducer.
AB  - The use of isopropyl-beta-D-thiogalactoside (IPTG) for induction of the lac
      promoter in small-scale cultivations is well established. However, for large
      scale microbiological processes the cost of this inducer is a severe limitation.
      Here is described a method by which lactose is used as inducer of the lac
      promoter with the same efficiency as that of IPTG. It was found that after growth
      on glucose the time of the addition of lactose is important for the quality of
      induction. The resulting yield of the recombinant protein increased when lactose
      was added to the culture if the glucose concentration was rather low. By careful
      monitoring of the glucose level in the fermentation, using a biosensor, it was
      possible to add the inducer when the carbon source was nearly depleted. Using
      Escherichia coli BL21 (pET3), in which was cloned the main antigen coat protein
      of the foot and mouth disease virus, induction of the gene led to expression of
      the target protein at a level exceeding 20% of the total cell protein.

PMID- 1369365
TI  - Influence of short-chain fatty acids on the production of spiramycin by
      Streptomyces ambofaciens.
AB  - The addition of short-chain fatty acids stimulates the production of spiramycin
      by Streptomyces ambofaciens cultivated on dextrins and ammonium chloride. The
      fatty acids were activated by two enzymatic systems. The first system (acyl-CoA
      synthetases) was present only during the exponential phase. The second system
      (acylkinases coupled with acylphosphotransferases) was synthesized during the
      growth phase and during the stationary phase, in which spiramycin production
      started. Short-chain fatty acids induced the synthesis of acylkinases and
      acylphosphotransferases. Added at the beginning of cultures, they increased the
      specific activity of these enzymes during the exponential growth phase. Added at
      the early stationary phase, the specific activity of these enzymes and of the
      spiramycin production increased. Excess ammonium in the culture considerably
      lowered the specific activity of acylkinases synthesized in the stationary phase,
      when spiramycin production started. This ammonium effect can be reduced by the
      addition of short-chain fatty acids.

PMID- 1369366
TI  - Receptor-based assays in screening for biologically active substances.
AB  - Molecular biology has identified new receptors and ligands which are deregulated
      in diseases such as cancer and autoimmune conditions and which provide rational
      targets for therapeutic intervention. Advances in instrumentation and methodology
      make it possible to screen large numbers of samples in simple receptor-ligand
      binding assays in the search for drug candidates. Caution must be exercised in
      the interpretation of data derived from such assays. This is particularly
      pertinent to the recently characterized receptors, such as the cytokine
      receptors, as we do not fully understand the relationship between the receptor
      type and the linkage of receptors to the appropriate or inappropriate second
      messenger systems that are used in the experimental screening protocols and the
      disease state.

PMID- 1369367
TI  - Monitoring a genetically engineered bacterium in a freshwater environment by
      rapid enzymatic amplification of a synthetic DNA "number-plate".
AB  - In order to set up a sensitive and reliable detection method to monitor
      environmentally released genetically engineered microorganisms (GEMs) a 72-bp,
      double-stranded DNA fragment has been built by annealing and ligating four
      synthetic oligonucleotides. Binding sites for two 20-mer oligonucleotides are
      situated inside the DNA fragment, flanking the centre. Into the central part of
      the construction a 30-nucleotide identification sequence has been fitted. Thanks
      to the presence of the two oligonucleotide binding sites, the synthetic
      construction ("number-plate") can be submitted to enzymatic amplification using
      the polymerase chain reaction (PCR), thus enabling the identification system to
      take advantage of the outstanding sensitivity of this technique. When released
      into a freshwater microcosm, cells of Pseudomonas putida carrying a "number
      plated" chromosome could be easily and rapidly detected merely by submitting
      boiled cell sediments to PCR amplification.

PMID- 1369368
TI  - Enzyme immobilization on a low-cost magnetic support: kinetic studies on
      immobilized and coimmobilized glucose oxidase and glucoamylase.
AB  - Glucose oxidase (GOx) and glucoamylase (GA) were immobilized and coimmobilized
      through their carbohydrate moieties onto polyethyleneimine-coated magnetite
      crosslinked with glutaraldehyde and derivatized with adipic dihydrazide. The
      carbohydrates were oxidized with sodium periodate, and at optimal concentration,
      their Vm increased up to 18% for GOx and up to 16% for GA. After immobilization,
      a remaining activity as high as 88% and 70% for GA with maltose and maltodextrin
      respectively as substrates was obtained, independently of the particle loading.
      On the contrary, the remaining activity of GOx strongly decreased at high
      particle loading. Nevertheless, half of its initial activity was recovered at low
      loading and was not significantly affected when GA was coimmobilized by
      saturating the reactive groups left on the particle. The Vm of both immobilized
      enzymes was improved by crosslinking their carbohydrates with adipic dihydrazide,
      a treatment which allows further coimmobilization of the other enzyme on a second
      layer.

PMID- 1369369
TI  - Factor(s) required by EBV transformed lymphocytes to grow under limiting dilution
      conditions.
AB  - IL-6 was demonstrated to promote growth of EBV transformed lymphocytes. However
      IL-6 was ineffective at promoting growth of EBV transformed lymphocytes cultured
      at the single cell level under limiting dilution conditions. On the contrary,
      HECS, which is known to contain IL-6, supported very efficiently the growth of 1
      2 EBV transformed cells. When IL-6 was removed from HECS, by using specific
      antibodies, no reduction in HECS activity was observed, indicating that probably
      more than one growth factor is required to support the growth of EBV transformed
      cells cultured at very low cell numbers in the absence of feeder cells.

PMID- 1369370
TI  - Structure-function analyses for aminoglycoside 3'-phosphotransferase II (APH(3')
      II).
AB  - Mutant strains containing APH(3')-II were constructed via site-directed
      mutagenesis of the cloned gene and by random mutagenesis of a strain containing
      the APH(3')-II gene on a conjugative plasmid. Substitutions at highly conserved
      amino acid residues produced APH(3') enzymes which in general showed reduced
      activity and conferred reduced levels of resistance to their substrates.
      Substitutions at Tyr 218 altered substrate specificity for the enzymes. Random
      mutagenesis produced plasmid-borne mutations conferring amikacin resistance. Two
      of these mutations appeared to be localized to the APH(3')-II structural gene.

PMID- 1369371
TI  - Improvement of recombinant gene expression in Escherichia coli for glucose
      controlled continuous and fed-batch cultures.
AB  - Escherichia coli TG1 (pHRW500) permanently expressed the human interferon alpha 1
      gene (ifn alpha 1) directed by the tryptophan promoter (trpP.O) during continuous
      and fed-batch cultivation with a limited supply of glucose. The expression of ifn
      alpha 1 could be improved after insertion of the catabolite activator region
      (cap) upstream to trpP.O during cultivation of the modified E. coli
      TG1(pHRW500cap) in glucose-controlled continuous and fed-batch cultures. The cap
      mediated stimulatory effect on the expression of cap-trpP.O-ifn alpha 1 increased
      with decreasing dilution rate. These results are in line with the increase in the
      level of cAMP with declining dilution rate and the well-known positive effects of
      cAMP-catabolite gene activator protein (CAP) at the transcriptional level. In
      addition, expression of the galactokinase gene (trpP.O-galK) in E. coli
      TG1(pDR720) could be improved in the same way with cap-trpP.O-galK in E. coli
      TG1(pDR720cap). Determinations of plasmid copy numbers, cellular amounts of
      galactokinase-mRNA, activity of galactokinase (AGalK) and the concentration of
      galactokinase at various dilution rates (D) strengthen the conclusion that the
      increase in AGalK with decreasing D was indeed due to the cap-mediated
      enhancement of transcription of the galK gene. We suggest that expression of
      other recombinant genes directed by various promoters that allow permanent
      transcription during growth with limited glucose supply in chemostat and fed
      batch fermentors can be improved by appropriate insertion of the cap region.

PMID- 1369372
TI  - S-Zephyr, a new high performance ion exchange chromatography column matrix.
AB  - S-Zephyr, a new column material for high performance cation exchange
      chromatography of proteins, is compared with Mono-S. The comparison is based on a
      retentivity study, a model separation of an artificial protein mixture, a sample
      load capacity experiment and the development of the separation performance at a
      column overload situation. S-Zephyr is found to be a good matrix for cation
      exchange chromatography, for analytical separations as well as for small and
      large scale protein purification applications.

PMID- 1369373
TI  - Selectable marker genes: safe for plants?

PMID- 1369374
TI  - Stabilization of Streptomyces lividans by homologous recombinational insertion.
AB  - We have developed a system for the introduction and maintenance of novel tandem
      repeats in the chromosome of Streptomyces lividans 66. This was achieved by
      introducing, via transformation, Escherichia coli "suicide" vectors carrying
      manipulated S. lividans DNA fragments. Selection for antibiotic resistance
      markers carried on such plasmids permitted the isolation and maintenance of
      mutant strains containing novel tandem repeats formed by the integration into the
      chromosome of the plasmids, via homologous recombination between plasmid-borne
      chromosomal sequences and identical sequences on the chromosome. When novel
      repeats were introduced, and maintained, in regions of the chromosome which
      become deleted in unstable strains of S. lividans, those deletion events were
      blocked. Surprisingly, such strains were also 10 to 20-fold more stable than the
      parent even in the absence of selection. In stable regions of the chromosome, the
      maintenance of novel repeats had no obvious effect on the deletion events. This
      strategy could be generally applicable to industrial strains of Streptomyces,
      where instability is a common problem.

PMID- 1369375
TI  - Accumulation of alkaliphilic Bacillus penicillinase cleaved within the signal
      sequence in cytoplasm of Escherichia coli.
AB  - Alkaliphilic Bacillus penicillinase produced by Escherichia coli is distributed
      in several subcellular compartments according to cultivation conditions. The
      penicillinase that accumulated in particular subcellular fractions of E. coli
      grown under different conditions was purified and characterized. Periplasmic or
      extracellular penicillinase (24 kDa) was mature protein, indicating that the
      putative precursor (27 kDa) was processed at the correct amino acid residue,
      probably by signal peptidase I. Cytoplasmic penicillinase contained two unusual
      proteins (25 kDa) that are produced by proteolytic cleavage of the precursor
      within its signal sequence.

PMID- 1369376
TI  - Thermostability of Pseudomonas hydrogenothermophila cytochrome c-552.

PMID- 1369377
TI  - Possible anti-tumor promoting properties of marine algae and in vivo activity of
      Wakame seaweed extract.

PMID- 1369378
TI  - Spin labeling and kinetic studies of a membrane-immobilized proteolytic enzyme.
AB  - Membrane-based bioreactors can greatly influence the rate and extent of chemical
      reactions and consequently lower the costs associated with the corresponding
      engineering processes. However, in order to progress in this area, greater
      understanding of the relationship of the structure and function of bioreactor
      systems is required. In this study, a proteolytic enzyme, papain (EC 3.4.22.2),
      was covalently coupled onto the surface of a vinyl alcohol/vinyl butyral
      copolymer (PVB) membrane employing either glutaraldehyde (GA) or 1,1'
      carbonyldiimidazole (CDI). Various kinetic and performance properties of the
      immobilized papain were studied. It was found that these characteristics of the
      membrane-bound papain depended on the immobilization method. The CDI-immobilized
      papain bioreactor was used, although the apparent Michaelis constant, Km, of the
      CDI-immobilized papain was larger than that of the GA-immobilized enzyme. In
      separate experiments, a six-carbon spacer was also used between the membrane
      support and the covalently-linked enzyme. It was found that the insertion of the
      spacer reduced the disturbance of the enzyme system, resulting in a decreased Km,
      which was now closer to the value for the free enzyme. Electron paramagnetic
      resonance (EPR) techniques of spin labeling were used for the first time to
      examine the conformational change and the active site structure of an enzyme
      covalently immobilized to a membrane. The structural changes of the active site
      of papain upon immobilization with and without a spacer were in agreement with
      the functional properties of the enzyme.

PMID- 1369379
TI  - Regulation of gene expression by thyroid hormones and retinoic acid.

PMID- 1369380
TI  - Novel applications of the ubiquitin-dependent proteolytic pathway in plant
      genetic engineering.
AB  - One goal of plant genetic engineering is the manipulation of protein levels
      within crop plants. New insights into the ubiquitin-dependent proteolytic pathway
      provide potential novel ways of enhancing levels of desired proteins by
      synthesizing them as ubiquitin fusions, and reducing levels of undesired proteins
      by selective protein degradation. As a result, the ubiquitin pathway should
      become a useful tool for many aspects of plant biotechnology.

PMID- 1369381
TI  - Antiviral activity of metabolites of T-2 toxin against herpes simplex virus type
      2.

PMID- 1369382
TI  - Expression and purification of recombinant 3C proteinase of Coxsackievirus B3.
AB  - We have cloned various lengths of coxsackievirus B3 cDNA encompassing the region
      encoding the 3C proteinase, which is essential to the viral replication cycle.
      Such viral cDNAs were fused in frame to the 5'terminal portion of the lacZ' gene
      carried on the vector pUC118 to express mature 3C proteinase in Escherichia coli.
      In the E. coli cells containing pCXB108 or pCXB117, constructed for this study, a
      large amount of 23-kDa protein was synthesized in the presence of IPTG. This
      protein was purified and was shown to be intact 3C proteinase. These data suggest
      that 3C proteinase, expressed as a part of a fusion protein, was active in E.
      coli and released itself from the precursor fusion protein by autocatalytic
      cleavage.

PMID- 1369384
TI  - A trial of peptide synthesis using angiotensin-I converting enzyme (ACE).

PMID- 1369383
TI  - Chalcone tetramers, lophirachalcone and alatachalcone, from Lophira alata as
      possible anti-tumor promoters.
AB  - Two chalcone tetramers were isolated as inhibitors of Epstein-Barr virus (EBV)
      activation induced by a tumor promoter, teleocidin B-4, from a medicinal plant in
      tropical west Africa, Lophira alata (Ochnaceae). One of them was identified as
      lophirachalcone. The other, named alatachalcone, was new, and the structure was
      determined by spectral properties. Both compounds also showed potent inhibitory
      activities against teleocidin B-4-induced inflammation on mouse ear. In an
      initiation-promotion experiment on mouse skin, alatachalcone (16 nmol)
      significantly inhibited tumor promotion caused by 12-O-tetradecanoylphorbol-13
      acetate (TPA, 1.6 nmol).

PMID- 1369385
TI  - Steroidal saponins from Smilax riparia and S. china.
AB  - Two new neotigogenin glycosides were isolated from the rhizomes and roots of
      Smilax riparia and a new isonarthogenin glycoside from those of S. china. The
      structures were elucidated by a combination of spectroscopic analysis and
      hydrolysis followed by spectral and chromatographic analysis. Several known
      saponins were also isolated and identified. The inhibitory activity of the
      saponins on cAMP phosphodiesterase was examined.

PMID- 1369386
TI  - Steroidal saponins from the rhizomes of Smilax sieboldii.
AB  - Six new steroidal saponins were isolated from the rhizomes of Smilax sieboldii.
      Their structures were determined by spectroscopic analysis and hydrolysis to be 3
      beta-hydroxy-(25R)-5 alpha-spirostan-6-one (laxogenin) 3-O-beta-D-glucopyranosyl
      (1----4)-O-[alpha-L-arabinopyranosyl-(1- ---6)]-beta-D-glucopyranoside, laxogenin
      3-O-alpha-L-arabinopyranosyl-(1----6)-beta-D-glucopyranoside, 3 beta,27-dihydroxy
      (25S)-5 alpha-spirostan-6-one 3-O-beta-D-glucopyranosyl-(1----4)-O-[alpha-L
      arabinopyranosyl-(1- ---6)]- beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-3
      beta,22 xi,26-trihydroxy-(25R)-5 alpha-furostan-6-one 3-O-alpha-L
      arabinopyranosyl-(1----6)-beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-3
      beta,22 xi,26-trihydroxy-(25R)-5 alpha-furostan-6- one 3-O-beta-D-glucopyranosyl
      (1----4)-O-[alpha-L-arabinopyranosyl-(1- ---6)]- beta-D-glucopyranoside and (25R)
      5 alpha-spirostan-3 beta-ol (tigogenin) 3-O-beta-D-glucopyranosyl-(1----4)-O
      [alpha-L-arabinopyranosyl- (1----6)]-beta-D-glucopyranoside. The inhibition of
      cAMP phosphodiesterase by the saponins was evaluated.

PMID- 1369387
TI  - Multilocus DNA fingerprint analysis of cell banks: stability studies and culture
      identification in human B-lymphoblastoid and mammalian cell lines.
AB  - The technique of multilocus DNA fingerprinting has great potential for the
      authentication of animal cell cultures and in identification of cross
      contamination. The Alec Jeffreys probes 33.6 and 33.15 were used as multilocus
      probes to demonstrate the consistent DNA fingerprint profiles in human peripheral
      blood and its derivative Epstein-Barr virus (EBV) transformed B-lymphoblastoid
      cultures maintained by repeated subculture for six months. However, fingerprint
      analysis of EBV transformed cultures generated from small numbers of cells showed
      that the majority (seven of eight cultures) had anomalous profiles. Some of these
      altered profiles shared common features not seen in the peripheral blood pattern.
      Analysis of seven murine hybridoma clones from a single fusion experiment
      revealed only two clones which could not be distinguished using probe 33.15.
      Further studies of master and distribution cell banks for eleven cell lines
      demonstrated consistent fingerprint profiles in all cases except one (U937).
      However, this cell line showed only minor differences in the master and
      distribution bank profiles. These data indicate that, while changes in
      fingerprint profile may be identified in exceptional instances, the multilocus
      fingerprinting method using probes 33.6 and 33.15 is a powerful and reliable tool
      in the quality control of animal cell cultures.

PMID- 1369388
TI  - Genetic engineering strategies for environmental applications.
AB  - Environmental applications of genetically engineered microorganisms are currently
      hampered not only by legal regulations restricting their release, but also by the
      frequent dearth of adequate genetic tools for their construction in the
      laboratory. Recent approaches to strain development include the use of non
      antibiotic markers as selection determinants, the use of transposon-vectors for
      the permanent acquisition of recombinant genes, and the utilization of expression
      devices based on promoters from promiscuous plasmids and biodegradative pathway
      genes.

PMID- 1369389
TI  - Jatropham derivatives and steroidal saponins from the bulbs of Lilium hansonii.
AB  - Two new jatropham derivatives and three new steroidal saponins were isolated from
      the fresh bulbs of Lilium hansonii, along with previously known compounds. The
      structures of the new compounds were elucidated, on the basis of spectroscopic
      data and chemical evidence, and by comparing them with those of known compounds,
      as (-)-5-hydroxy-3-methyl-3-pyrrolin-2-one (jatropham) 5-O-beta-D-glucopyranosyl
      (1----3)-beta-D-glucopyranoside, (2S*,4R*)-1-(3-methyl-2-oxo-3-pyrrolinyl)-4
      methyl-5-oxo-2-pyrr olidinecarboxyli c acid, 26-O-beta-D-glucopyranosyl-(25R)-5
      alpha-furostan-3 beta,22 zeta-diol 3-O-alpha-L-rhamnopyranosyl-(1----2)-O-[beta-D
      glucopyranosyl-(1----4)]- beta-D-glucopyranoside, (25R)-5 alpha-spirostan-3
      beta,12 alpha-diol 3-O-alpha-L-rhamnopyranosyl-(1----2)-O-[beta-D-glucopyranosyl
      (1----4)]- beta-D-glucopyranoside and (25R)-spirost-5-en-3 beta,12 alpha-diol 3-O
      alpha-L-rhamnopyranosyl-(1----2)-O-[beta-D-glucopyranosyl-(1----4)]- beta-D
      glucopyranoside, respectively. The stereostructure of jatropham dimer, the plain
      structure of which was presented previously, was confirmed by X-ray
      crystallographic analysis. The inhibitory activity on cyclic AMP
      phosphodiesterase of the steroidal saponins was evaluated.

PMID- 1369390
TI  - Diagnosis of mycobacterial infections by PCR and restriction enzyme digestion.
AB  - A method for the diagnosis of mycobacterial infections by PCR amplification
      followed by selective restriction enzyme digestion of the PCR product was
      developed. The amplified DNA sequence used in this study occurs within the gene
      encoding for the mycobacterial 65 kDa heat shock protein (Hance et al. 1989),
      which is found in all mycobacteria. However, there are minute differences in the
      amplified sequence from the Mycobacterium tuberculosis complex compared with the
      corresponding sequence from the Mycobacterium avium complex. These differences
      made it possible to rapidly identify to which mycobacterial complex a particular
      sample belonged by restriction enzyme digestion of the PCR product. A total of 66
      samples were tested and all of them were correctly identified. This and similar
      methods should provide a sensitive, specific and rapid (within 12 h) way of
      diagnosing mycobacterial infections to the species level.

PMID- 1369391
TI  - Protein hormones and their receptors.
AB  - Technological advances in the isolation and characterization of novel receptors
      have led to a significant increase in our understanding of protein-ligand binding
      to receptors and the means by which responses are triggered. Hormones and their
      receptors are composed of structurally conserved domains, and several ligands
      appear to use similar surface regions for receptor binding. A key event in signal
      transduction is the aggregation by the ligand of one or more receptor subunits,
      and this can include the sharing of subunits between different ligands. These
      findings have allowed the design of ligands with receptor-antagonist properties.

PMID- 1369392
TI  - Bioprocess development to improve foreign protein production from recombinant
      Streptomyces.
AB  - Bioprocessing strategies to improve production of the heterologous protein
      parathion hydrolase from recombinant Streptomyces lividans were investigated.
      Initial limitations to increased production were overcome by using large amounts
      of nutrients and feeding these nutrients throughout the fermentation. Batch
      addition of such large amounts of nutrients resulted in byproduct acid
      accumulation. Our data suggest that byproducts resulted from incomplete
      utilization of peptide medium ingredients and not from an overflow of glucose
      catabolism. Over extended fed-batch operation, oxygen transfer became limiting
      and these limitations were overcome by sparging oxygen-enriched gas. When
      cultivation was continued past about 90 h, we observed that despite nutrient
      feeding and oxygen enrichment enzyme activities no longer increased. Our results
      show that during such late cultivation periods the rates of enzyme synthesis and
      deactivation became balanced. If synthesis is prevented, either by a nutritional
      limitation or by the addition of the protein synthesis inhibitor chloramphenicol,
      enzyme activities were observed to decrease. Since deactivation rate constants in
      these experiments were similar to those observed in cell-free studies, and
      because extracellular protease activities were not detected in our fermentation,
      it appears that deactivation results from the inherent instability of the
      parathion hydrolase enzyme.

PMID- 1369394
TI  - Expansion of insecticidal host range of Bacillus thuringiensis by in vivo genetic
      recombination.
AB  - We describe a novel approach for the insertion of an insecticidal toxin gene into
      a resident plasmid in Bacillus thuringiensis (Bt). A gene encoding a coleopteran
      specific toxin was cloned within a fragment of IS232 and inserted into a plasmid
      thermosensitive for replication in Bt. The plasmid was used to transform a Bt
      strain toxic to lepidoptera, and the transformants were then selected at non
      permissive temperature for clones in which the vector had integrated into a copy
      of IS232 present on a resident plasmid. A second recombination event was selected
      such that the vector was eliminated and the newly introduced toxin gene was
      conserved. The resulting strain contained only DNA of Bt origin, and displayed
      insecticidal activity against both lepidoptera and coleoptera.

PMID- 1369393
TI  - Selection and isolation of bacteria capable of degrading dinoseb (2-sec-butyl-4,6
      dinitrophenol).
AB  - Dinoseb (2-sec-butyl-4,6-dinitrophenol) has been a widely used herbicide that
      persists in some contaminated soils, and has been found in groundwaters, causing
      health and environmental hazards. Persistence in some soils may stem from a lack
      of dinoseb-degrading organisms. We established a chemostat environment that was
      strongly selective for aerobic (liquid phase) and anaerobic (sediment phase)
      bacteria able to degrade dinoseb. The chemostat yielded five taxonomically
      diverse aerobic isolates that could transform dinoseb to reduced products under
      microaerophilic or denitrifying conditions, but these organisms were unable to
      degrade the entire dinoseb molecule, and the transformed products formed
      multimeric material. The chemostat also yielded an anaerobic consortium of
      bacteria that could completely degrade dinoseb to acetate and CO2 when the Eh of
      the medium was less than -200 mV. The consortium contained at least three
      morphologically different bacterial species. HPLC analysis indicated that dinoseb
      was degraded sequentially via several as yet unidentified products. Degradation
      of these intermediates was inhibited by addition of bromoethane sulfonic acid. GC
      MS analysis of metabolites in culture medium suggested that regiospecific attacks
      occurred non-sequentially on both the nitro groups and the side-chains of
      dinoseb. The consortium was also able to degrade 4,6-dinitro-o-cresol, 3,5
      dinitrobenzoic acid, 2,4-dinitrotoluene, and 2,6-dinitrotoluene via a similar
      series of intermediate products. The consortium was not able to degrade 2,4
      dinitrophenol. To our knowledge, this is the first report of strictly anaerobic
      biodegradation of an aromatic compound containing a multicarbon, saturated
      hydrocarbon side chain.

PMID- 1369395
TI  - Homogeneous gene assay.

PMID- 1369396
TI  - Cellular engineering for the treatment of metabolic disorders: prospects for
      therapy in diabetes.
AB  - Significant advances in the areas of identification of disease susceptibility
      genes and gene transfer technologies have fueled new initiatives in cellular
      engineering as a means for treating metabolic disease. This article utilizes new
      findings from such work as the blueprint for a discussion of the prospects for
      gene therapy in diabetes mellitus.

PMID- 1369397
TI  - Influence of transfected SV40 early region on growth and differentiation of human
      endothelial cells.
AB  - Endothelial cells isolated from human umbilical veins show a limited in vitro
      life span of about 40 population doublings. Cell division is dependent on the
      presence of endothelial cell growth factor in the culture medium. We have
      transfected primary endothelial cells with a plasmid containing the early region
      of SV40 virus. Large T positive cells were obtained which grew in the absence of
      endothelial cell growth factor at low serum concentrations and showed a prolonged
      lifespan. Expression of von Willebrand factor and SV40 large T antigen was
      detected simultaneously in transfected cells.

PMID- 1369398
TI  - Functional expression of GABAA chloride channels and benzodiazepine binding sites
      in baculovirus infected insect cells.
AB  - We have employed the baculovirus expression system for the production of insect
      cell membranes having GABA/benzodiazepine binding sites. Three recombinant
      baculoviruses each harboring a different GABAA receptor cDNA were introduced into
      insect cells by simultaneous infection. Infected cells expressed GABA responsive
      Cl- channels and benzodiazepine binding sites with the same pharmacological
      specificity as animal cells expressing these receptor subunits.

PMID- 1369399
TI  - Transgenic plants of tall fescue (Festuca arundinacea Schreb.) obtained by direct
      gene transfer to protoplasts.
AB  - Chimeric hygromycin phosphotransferase (hph) and phosphinothricin
      acetyltransferase (bar) genes were introduced, using polyethylene glycol
      treatment, into protoplasts isolated from embryogenic cell suspension cultures of
      tall fescue (Festuca arundinacea Schreb.), a graminaceous plant that is an
      important forage crop in temperate pastures. Colonies resistant to either 200
      mg/l hygromycin or 100 mg/l phosphinothricin, respectively, were recovered upon
      selection using bead-type culture systems. Stable integration of the transgenes
      in the genomes of plants regenerated from resistant callus clones was shown by
      Southern hybridization analysis. In situ hybridization of a labeled transgene
      probe to metaphase chromosomes is shown for one transgenic primary regenerant.
      Expression of the transgenes in mature plants was demonstrated by HPH enzyme
      assay or by phosphinothricin-herbicide spraying.

PMID- 1369401
TI  - Use of mammalian cell expression cloning systems to identify genes for cytokines,
      receptors, and regulatory proteins.
AB  - Mammalian cell expression cloning has become a standard technique for the
      isolation of mammalian genes or cDNAs. Its advantage is that the biological
      functions of the gene of interest are used for cloning. Therefore, the identified
      cDNAs or genes should be functional in vivo, and there is no need for physical or
      chemical information about the gene products, so that protein purification in
      sufficient quantity to raise antibodies or to obtain amino acid sequences is not
      necessary. Here, we summarize recent progress in mammalian cell cloning systems,
      and discuss the possible directions in which this technique will lead.

PMID- 1369400
TI  - Protein compositional analysis of inclusion bodies produced in recombinant
      Escherichia coli.
AB  - Culture conditions favouring the simultaneous formation of soluble protein and
      inclusion bodies (IBs) were chosen for producing the cytoplasmic protein beta
      galactosidase or the periplasmic protein TEM-beta-lactamase. Soluble and
      insoluble cell fractions of Escherichia coli producing either beta-galactosidase
      or TEM-beta-lactamase were analyzed by one- and two-dimensional gel
      electrophoresis and subsequent silver staining or immunodetection of the
      recombinant protein. The results show that truncated fragments of the recombinant
      protein were not present in the soluble cell fraction but accumulate in the IB
      fraction. The presence of other cellular, non-plasmid-encoded proteins in IB
      preparations such as the outer membrane proteins OmpF, OmpC, and OmpA or the
      ribosomal subunit proteins L7/L12 was attributed to co-precipitation of cell
      debris-associated components. Protein-folding enzymes were not detected in IB
      preparations. The specificity of in-vivo protein association in the formation of
      IBs and its implication on protein purification is discussed.

PMID- 1369402
TI  - Examples of expression systems based on animal RNA viruses: alphaviruses and
      influenza virus.
AB  - Successful recovery of RNA viruses and functional RNA replicons from cDNA has
      greatly facilitated molecular genetic analyses of viral proteins and cis
      regulatory elements. This technology allows the use of RNA virus replication
      machinery to express heterologous sequences. Both positive-strand and negative
      strand animal RNA viruses have been engineered to produce chimeric viruses
      expressing protective epitopes from other pathogens and for transient expression
      of heterologous sequences.

PMID- 1369403
TI  - Adeno-associated virus vectors.
AB  - Adeno-associated virus is a human parvovirus that integrates its DNA genome into
      host cell chromosomes with very high efficiency. This suggests that adeno
      associated virus may be a useful vector for human gene therapy. Interest in adeno
      associated virus vectors increased greatly in the last year following reports
      that adeno-associated virus genome integration may be site specific and occur at
      preferred sites in the human genome. Several genes relevant to the treatment of
      genetic or infectious diseases have been expressed in adeno-associated virus
      vectors in vitro.

PMID- 1369404
TI  - Biological fate of a polydisperse acrylate polymer in anaerobic sand-medium
      transport.
AB  - Soluble polyacrylate (PA), a polydisperse mixture of polyacrylate polymers, is
      strongly adsorbed and biodegradable. Biotic fate studies were carried out with
      once-through columns containing sand colonized with anaerobic biomass previously
      grown in a methanogenic fluidized bed. A fraction of soluble PA having a weight
      average molecular weight of 16,700 and a range of molecular weight from 10(3) to
      10(5) was biologically removed and mineralized to CO2. Due to its polydisperse
      nature, the breakthrough curve had a gradual increase to an apparent steady-state
      removal of approximately 60% near one day when the liquid detention time was 21
      minutes. Modeling successfully explained the observed breakthrough result when
      the fraction was divided into components having a wide range of retardation
      factors (R): about 25% was strongly adsorbed (R = 200 and 500), 45% was
      moderately adsorbed (R = 50 and 100), and 30% was weakly adsorbed (R = 1-10). In
      this study, in which active biomass already was present from utilization of a
      primary substrate (glucose here), equilibrium adsorption increased the time to
      breakthrough, which also reduced the exiting concentration by increasing the
      substrate contact time.

PMID- 1369405
TI  - Generation and characterization of a monoclonal antibody specific for the major
      thiol-activated cysteine proteinase of Porphyromonas gingivalis W83.
AB  - An IgM monoclonal antibody specified for the thiol-activated proteinase of the
      oral pathogen Porphyromonas gingivalis W83 was generated. The antibody reacted
      with a single protein of approximate molecular mass 43 kDa in outer membrane
      preparations of P. gingivalis. Immuno-electron microscopy using the monoclonal
      antibody and immunogold labelling confirmed the cell surface location of the
      thiol-activated proteinase. The monoclonal antibody failed to detect any proteins
      in Western blot analysis of other closely related oral bacteria. The specificity
      of this monoclonal antibody to the thiol-activated proteinase of P. gingivalis
      should allow its use as a diagnostic tool for the rapid enumeration of P.
      gingivalis in clinical samples.

PMID- 1369406
TI  - Effects of oxygen on recombinant protein production by suspension cultures of
      Spodoptera frugiperda (Sf-9) insect cells.
AB  - Spodoptera frugiperda (Sf-9) insect cells have been grown in serum-free medium in
      250-ml spinner flasks. The maximum cell density obtained in these cultures was
      dependent on the aeration rate of the culture. Similar yields of uninfected cells
      were obtained when cultures were stirred in spinner flasks at 80 rev min-1 and in
      a 4-1 stirred-tank bioreactor and the dissolved oxygen in the bioreactor was
      controlled at 20% of air saturation. Cells were infected with a recombinant
      baculovirus at different multiplicities of infection: the timing and maximum
      level of expression of the recombinant protein were dependent on the multiplicity
      of infection, the cell density at infection, and on the aeration rate of the
      culture. Oxygen-limited growth resulted in undetectable levels of recombinant
      protein (< 6 ng recombinant protein 10(-7) cells). Compared with the maximum
      yields observed in spinner flask cultures, higher levels of recombinant protein
      were produced when cells were grown and infected in the bioreactor. The level of
      dissolved oxygen in the bioreactor was controlled at 50% of air saturation.

PMID- 1369407
TI  - Stimulation of the onset of sporulation of Clostridium perfringens type A by
      netropsin and distamycin.
AB  - The basic peptide antibiotics, netropsin and distamycin, previously shown to
      inhibit sporulation of Bacillus subtilis, stimulated low levels of sporulation of
      Clostridium perfringens strain NCTC 8798 at concentrations of 1.0 and 0.1
      microgram/ml respectively. Most sporulating cells produced in the presence of the
      antibiotics were defective. These were blocked at Stage III of sporulation, and
      many possessed forespores exterior to the sporangium. The same antibiotics could
      also inhibit the caffeine-induced stimulation of sporulation of this strain.

PMID- 1369408
TI  - Extraordinary stability of enzymes dried in trehalose: simplified molecular
      biology.
AB  - We show that extremely fragile biomolecules such as DNA restriction and modifying
      enzymes can be dried in vitro in the presence of trehalose with no loss of
      activity, even after prolonged storage. A remarkable and unexpected property of
      the dried enzyme preparations is their ability to withstand prolonged exposure to
      temperatures as high as +70 degrees C. This stability is unique to trehalose and
      is not found with other sugars irrespective of their physical or chemical
      properties. The immediate significance of these observations is the ability to
      convert enzymes used in molecular biology into stable reagents. The indefinite
      stability and high temperature tolerance of these dried enzymes should permit the
      design of convenient formats that may be of particular significance in the
      automation of genome mapping and sequencing projects. The stabilization of a wide
      range of biomolecules by trehalose also has practical implications for a number
      of areas ranging from basic science, through healthcare and agriculture, to bio
      electronics.

PMID- 1369410
TI  - Inhibitory effect of acylphloroglucinol derivatives on the replication of
      vesicular stomatitis virus.
AB  - The antiviral activity of natural phloroglucinols and of synthesized mono- and
      diacylphloroglucinols, and 2,6-diacyl-4,4-dialkylcyclohexa-1,3,5-triones was
      investigated. A correlation between the acyl chain length and inhibitory activity
      against vesicular stomatitis virus (VSV) was observed. Potent antiviral activity
      was found in di-isovalerylphoroglucinol. 2,6-Diacyl-4,4-dialkylcyclohexa-1,3,5
      triones inhibited replication of the virus with low cytotoxicity.

PMID- 1369409
TI  - The effect of signal sequences on the efficiency of secretion of a heterologous
      phosphotriesterase by Streptomyces lividans.
AB  - A heterologous phosphotriesterase (parathion hydrolase) containing the native
      Flavobacterium species signal sequence was previously shown to be secreted by
      Streptomyces lividans. Western blot analysis of the recombinant
      phosphotriesterase produced by S. lividans demonstrated only the mature form
      extracellularly but both processed and unprocessed forms in cell-associated
      samples. To investigate the efficiency of secretion in Streptomyces, a
      construction was made that substituted a native Streptomyces beta-galactosidase
      signal sequence for the Flavobacterium signal sequence. This resulted in a higher
      proportion of hydrolase in the extracellular fluid and a lower proportion of
      parathion hydrolase remaining cell-associated. These results suggest that use of
      a native Streptomyces signal sequence may result in more efficient secretion of
      heterologous proteins.

PMID- 1369411
TI  - Epiderstatin induces the flat reversion of NRK cells transformed by temperature
      sensitive Rous sarcoma virus.
AB  - Epiderstatin is a unique glutarimide antibiotic which was found by screening for
      inhibitors of the signal transduction of epidermal growth factor (EGF). The
      antibiotic (0.01 microM) was found to reverse the morphology of NRK cells that
      were infected with a temperature-sensitive mutant of Rous sarcoma virus (srcts
      NRK) from the transformed phenotype to the normal phenotype at the permissive
      temperature (32 degrees C). Epiderstatin did not inhibit the protein kinase
      activity of p60v-src. The cell cycle progression of src(ts)-NRK cells was blocked
      at G0/G1 phase, which was caused by the inhibition of biosynthesis of p60v-src
      but not the transcription of v-src mRNA.

PMID- 1369412
TI  - Control of in vivo proteolysis in the production of recombinant proteins.
AB  - Proteolytic degradation of protein products causes many problems in the
      bioprocess industry. The increasing production of proteins in heterologous hosts
      through the use of recombinant DNA technology, has recently brought the problem
      into focus, since it seems that heterologous proteins are more prone to
      proteolysis. The result of proteolytic attack may vary from complete hydrolysis
      of the product to minor truncation of the protein without impairment of its
      biological function. The degree to which such partial proteolysis is a problem
      depends on the requirements of the ultimate use of the protein product.

PMID- 1369414
TI  - Tests to combat lentiviruses in domestic animals. Biotechnology Research Group.
AB  - Since the discovery of human immunodeficiency virus (HIV) as the cause of AIDS
      the study of other members of the virus group lentivirinal has intensified. A
      major outcome of this research have been the development of "state of the art"
      diagnostic tests. While it has long been realised that these viruses were
      important causes of slowly developing diseases in sheep and horses other
      lentiviruses have recently been implicated in similar disease situations in
      goats, cats and cattle. Membership of the lentivirus group of viruses has
      increased dramatically over the past fifteen years and it is likely that most if
      not all mammalian species will be found to be infected with their own lentivirus.
      This paper will describe the problems caused by these viruses in domestic animals
      and the steps being taken to prevent their spread. Biotechnology companies have a
      major role in devising simple and economical tests to detect the viruses and
      antibodies to these viruses. In addition if a vaccine can be produced against any
      of the animal viruses this will perhaps enable a similar vaccine to be prepared
      against HIV.

PMID- 1369413
TI  - Multiple drug-resistance in variant of a human non-small cell lung carcinoma cell
      line, DLKP-A.
AB  - A 300-fold adriamycin resistant variant (DLKP-A) of the human lung squamous cell
      carcinoma line DLKP was established by stepwise selection in increasing
      concentrations of adriamycin. Different levels of cross-resistance were observed
      towards VP-16, VM-26, colchicine, vincristine and, somewhat unexpectedly, cis
      platin. Resistance was stable for at least 3 months in culture in the absence of
      drug. P-glycoprotein overexpression was detected by immunofluorescence and
      Western Blotting, and a direct causal role for P-glycoprotein overexpression in
      the resistant phenotype was established by transfection with an mdr1 specific
      antisense oligonucleotide. A modified cryopreservation procedure was necessary
      for the resistant variant line. The resistant population displays clonal
      heterogeneity with respect to resistance level. A higher frequency of double
      minute chromosomes was observed in DLKP-A when compared with the parental cell
      line.

PMID- 1369415
TI  - Transcriptional regulation by the nuclear receptor superfamily.
AB  - In the past year, additional experimental data have expanded our understanding of
      the molecular mechanisms that underlie nuclear receptor control of regulatory
      programs. It is increasingly clear that steroid members (e.g. glucocorticoid and
      estrogen) and non-steroid members (e.g. retinoic acid, thyroid hormone, and
      vitamin D) of the nuclear receptor superfamily may utilize distinct strategies in
      achieving their complex control of gene regulation.

PMID- 1369416
TI  - Viral proteases as targets for chemotherapeutic intervention.
AB  - Many viruses encode proteinases that are essential for infectivity, and are
      consequently attractive chemotherapeutic targets. The biochemistry and structure
      of the human immunodeficiency virus proteinase have been characterized
      extensively, and potent peptide-mimetic inhibitors have been developed.
      Techniques and strategies used to improve the efficiency of these compounds are
      likely to be applicable to other viral proteinases.

PMID- 1369417
TI  - Neutrophil adhesion: a point for therapeutic intervention?
AB  - It has become increasingly clear over the last 20 years that the potential exists
      to modulate inflammatory responses with compounds that interfere with
      intercellular adhesion. This review highlights the adhesion interactions that
      occur during neutrophil extravasation and indicates some of the possible ways of
      disrupting these interactions.

PMID- 1369418
TI  - Transformation of vitamin D3 to 1 alpha,25-dihydroxyvitamin D3 via 25
      hydroxyvitamin D3 using Amycolata sp. strains.
AB  - To enzymatically synthesize active metabolites of vitamin D3, we screened about
      500 bacterial strains and 450 fungal strains, of which 12 strains were able to
      convert vitamin D3 to 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] via 25
      hydroxyvitamin D3 [25(OH)D3]. The conversion activity was only detected in
      strains belonging to the genus Amycolata among all the organisms tested. A
      preparative-scale conversion of vitamin D3 to 25(OH)D3 and 1 alpha,25(OH)2D3 in a
      200-1 tank fermentor using A. autotrophica FERM BP-1573 was accomplished,
      yielding 8.3 mg 25(OH)D3/l culture and 0.17 mg 1 alpha,25(OH)2D3/l culture. A
      related compound, vitamin D2, could be also converted to 25-hydroxyvitamin D2 and
      1 alpha,25-dihydroxyvitamin D2 using the same strain. The cytochrome P-450 of
      FERM BP-1573 was detected by reduced CO difference spectra in whole-cell
      suspensions. Vitamin D3 in the culture induced cytochrome P-450 and the
      conversion activity simultaneously, suggesting that the hydroxylation at C-25 of
      vitamin D3 and at C-1 of 25(OH)D3 originates from cytochrome P-450.

PMID- 1369419
TI  - An integrated process for the production and biotransformation of penicillin.
AB  - The extraction of Penicillin G (PG) from the filtered cultivation medium of
      Penicillium chrysogenum and its conversion into 6-amino penicillanic acid (6-APA)
      and phenyl acetic acid (PhA) at pH 8 was performed in a 10 l kuhni extractor
      during the production by means of penicillin-G-amidase immobilized in a liquid
      membrane carrier system (LM). 6-APA was enriched in LM, and the PhA returned to
      the cultivation medium. After electrocoalescence of LM, the 6-APA was converted
      into ampicillin with the same enzyme at pH 6, while the liquid membrane phase and
      enzyme were recycled and reused.

PMID- 1369420
TI  - Transformation of Bowes melanoma cells with SV40 T antigen.
AB  - A serum-dependent and two serum-independent variants of the Bowes melanoma cell
      line, RPMI7272, were transfected with plasmids containing a geneticin-resistance
      (neo) gene transcribed by the HSV thymidine kinase promoter and an SV40 T antigen
      gene under control of the mouse metallothionein I promoter. T-antigen increased
      the cloning efficiency of the serum-dependent cell line in soft-agar more than 50
      fold, but cloning efficiency of serum-independent lines was not increased.
      Trypsinization of serum-independent lines required 100 times lower concentrations
      of trypsin than serum-dependent cells. Human metal-inducible T-antigen-producing
      (HMT) melanoma cells supported replication of transfected plasmids containing an
      SV40 origin of replication. Transient expression of interferon or plasminogen
      activator from such plasmids was 40-fold higher than in untransformed melanoma
      cells and could be enhanced 30-fold more by stimulation of transcription of the T
      antigen gene with cadmium chloride. HMT cells can be grown in suspension and thus
      may represent an attractive alternative to monkey kidney COS cells.

PMID- 1369421
TI  - Superfamily structure and biotech drug development.

PMID- 1369422
TI  - Solubilization and activity of proteins in compressible-fluid based
      microemulsions.
AB  - We have used the pressure dependency of density in near critical propane to
      design a novel protein extraction system. Active, structurally intact, proteins
      have been extracted from an aqueous phase into subcritical propane containing the
      non-ionic detergent polyoxyethylene sorbitan trioleate (Tween-85). The pressure
      dependence of protein transfer from the aqueous to organic phase is described for
      cytochrome C and subtilisin. The effect of the microemulsion and compressible
      propane on protein structure and function is also discussed. The first
      determinations of kinetic constants for an enzyme-catalyzed reaction in such a
      system are also presented.

PMID- 1369423
TI  - Separation of X- and Y-chromosome-bearing murine sperm by free-flow
      electrophoresis: evaluation of separation using PCR.
AB  - The effectiveness of separation of murine X- and Y-bearing sperm by free-flow
      electrophoresis was evaluated by the polymerase chain reaction (PCR). The ratio
      of X- and Y-bearing sperm from cauda epididymis was analyzed before and after
      free-flow electrophoresis. A Y-chromosome-specific sequence (pY353/B) and an
      autosomal sequence (myogenin) were used to estimate the ratio between X- and Y
      sperm in the separated fractions. Cauda epididymal mice sperm were separated into
      two peak fractions under the electric field. Each peak fraction contained sperm
      of normal shape, however, the motility of the sperm was extremely diminished
      after separation by electrophoresis. DNA was extracted from 10(4) sperm from each
      fraction and from the unseparated sperm, and Y-chromosome specific PCR was
      performed. The PCR experiment revealed that fraction No. 16 (the peak near the
      cathode) was a Y-sperm rich fraction, whereas fraction No. 22 (the peak near the
      anode) was a Y-sperm poor one. These results suggested that murine X- and Y-sperm
      could be successfully separated by free-flow electrophoresis. Analysis of the
      chromosome-specific sequence by PCR was demonstrated to be a direct and adequate
      method to evaluate the separation of X- and Y-sperm.

PMID- 1369424
TI  - Beneficial effect of hydrotropes on partitioning behaviour of proteins in aqueous
      two phase systems.
AB  - Proteins have been partitioned in poly(ethylene glycol) (PEG)-salt systems
      containing hydrotropes. Hydrotropes are surface active compounds with strong
      ionic nature with a smaller hydrophobic part as compared to surfactants. The
      effect of pH, hydrotrope concentration, polymer molecular weight and protein
      molecular weight on partitioning of proteins including enzymes and their
      separation has been investigated. The effects of hydrotropes may be explained on
      the basis of interaction of PEG and the hydrotropes. This is substantiated by
      measuring the concentration of hydrotropes in both the phases. The practical
      utilization of the described effect is to enhance the separation of a mixture of
      proteins by many folds. Preliminary experiments have shown that hydrotropes at
      low concentrations do not affect enzyme activity and do not have any bactericidal
      activity.

PMID- 1369425
TI  - Hydrophobic interaction chromatography of recombinant human growth hormone,
      Genotropin.
AB  - A recombinant human growth hormone preparation (rhGH) has been used to study the
      effects of temperature, pH and detergent (Brij 35) concentration on the
      selectivity, recovery and retention time, during hydrophobic interaction
      chromatography (HI-HPLC) on a TSK-phenyl-5PW column. The rhGH preparation used in
      the study contained two rhGH variants, e.g. LMWGH and Clip I. These variants are
      structurally very similar to rhGH and exhibited very similar chromatographic
      behaviour to rhGH, important in evaluation of selectivity. Structural studies
      revealed that LMWGH had lost the first N-terminal amino acid residue,
      phenylalanine. Clip I exhibited an increased molecular mass of 32.7 Da for the C
      terminal tryptic fragment T18-T19. Temperature and pH were found to influence
      retention time, sharpness of peaks and selectivity. Furthermore, recoveries were
      improved from 50% to 99% for rhGH upon the introduction of 0.075% Brij 35, a non
      ionic detergent, in the presence of 5% acetonitrile. The optimized HI-HPLC system
      was found to exhibit good recoveries and excellent selectivity. The system is
      suitable both as an in-process chromatographic purification step for rhGH, as
      well as an analytical test method for purity and potency.

PMID- 1369426
TI  - Purification of bacterial exotoxins. The case of botulinum, tetanus, anthrax,
      pertussis and cholera toxins.
AB  - Bacterial protein toxins and their fragments have been isolated and purified for
      various reasons, including the development of efficient vaccines and for methods
      of identification of bacterial agents causing disease. This activity continues
      today but a new area of bacterial protein toxin research has recently emerged.
      Since it was shown that toxin molecules comprise several types of biological
      activity within their structural domains, it was suggested to use these domains
      (and their combinations) as biochemical tools for developing novel agents for
      disease imaging and and/or relieving. In this way eukaryotic cell-receptor
      specific fusion toxins have been developed to prevent malignancy in human. While
      human clinical trials of these preparations have only recently begun, the
      preliminary clinical findings are promising. Also fusion proteins which combine
      independent immunodominant epitopes from different antigens have also been
      developed thus opening a way for the generation of new vaccines for both human
      and veterinary use. Receptor binding fragments of microbial toxins when combined
      with other molecules may be useful in delivering these molecules into the cell.
      In this way novel agents may be developed with a potential for inducing specific
      changes at the molecular level for the correction of metabolic disorders causing
      human and animal diseases. Bacterial protein toxins such as anthrax, botulinum,
      cholera, pertussis and tetanus for which considerable progress has been achieved
      in structure-function analysis are promising candidates for such research.
      Particularly exciting appears the idea of extending this research to the cells of
      the nervous system, exploiting the unique specificity of the botulinum or tetanus
      toxin fragments which may bring long desired methods for treatment of various
      disorders of the nervous system. Data on functional domains of these toxins as
      well as methods of purification of the whole toxins and their fragments are
      considered in this review as they form a base for their further structure
      function analysis and engineering applications.

PMID- 1369427
TI  - Shear thickening of DNA in SDS lysates.
AB  - Cells of Escherichia coli were subjected to lysis by an alkali detergent
      treatment (sodium dodecyl sulphate). The rate of detergent lysis was not first
      order. The rheological properties of the lysate were measured using a controlled
      stress rheometer. Detergent-lysed cells produced a lysate which showed marked non
      Newtonian properties. The material showed a shear thickening at specific low
      shear stress conditions. The acceleration of the cone during the ascent stage of
      a flow curve, influenced the shape of the flow curves. These findings are
      discussed in relation to the form of bacterial DNA in solution.

PMID- 1369428
TI  - Metal-based affinity separation of alpha- and gamma-chymotrypsin and thermal
      stability analysis of isolates.
AB  - Chymotrypsin preparations are contaminated by autolysis products and other post
      translational products derived from the zymogen. Some prevalent contaminants are
      difficult to detect with activity assays and molecular weight separation.
      However, our differential scanning calorimetry (DSC) studies of alpha
      chymotrypsin have revealed that gamma-chymotrypsin is a common contaminant in
      commercial preparations, and the alpha- and gamma-species differ significantly in
      thermal stability. Thus, DSC analysis provides a sensitive and rapid means to
      assess the homogeneity of preparations. Moreover, free metal ion binding studies
      conducted indicate that the alpha- and gamma-species differ substantially in the
      number of metal binding sites and metal affinity. Therefore, to attempt to
      repurify a commercial preparation of alpha-chymotrypsin, a resolubilized sample
      of alpha-chymotrypsin was subjected to immobilized metal (Cu+2) affinity
      chromatography with pH elution and the fractions were subjected to DSC analysis.
      The process successfully removed the majority of the contaminating gamma
      chymotrypsin.

PMID- 1369429
TI  - Interfacial protein adsorption and inactivation.
AB  - Protein inactivations at liquid-liquid, gas-liquid, and liquid-solid interfaces
      are presented. Wherever possible the mechanisms of protein inactivation, the
      extent of inactivation, and means by which this inactivation may be minimized are
      presented. Emphasis is placed on the 'quality' or the heterogeneity of the
      protein absorbed at the different types of interfaces. The analysis of the
      adsorption of proteins at different types of interfaces presented together
      provides novel physical insights into protein interactions at interfaces. The
      influence of protein adsorption at interfaces on bioseparations is analyzed by
      discussing examples on two-phase separations, fermentation systems, membrane
      separation systems, and chromatographic separations. Valuable knowledge gained
      during protein adsorption for biomedical applications may be applied with caution
      to bioseparation systems wherever appropriate. Future theoretical and
      experimental analysis on protein adsorption in bioseparation systems should pay
      more attention to the 'quality' of the protein adsorbed at the interface.

PMID- 1369431
TI  - Plasmin cleavage of human beta-casein.

PMID- 1369430
TI  - Mathematical modelling and simulation of aqueous two-phase continuous protein
      extraction.
AB  - A mathematical model has been developed to describe the continuous, steady-state
      operation of an aqueous two-phase system for protein extraction. The model is
      based on steady-state mass balances of the main components and phase equilibrium
      data. Experimental data on the separation of thaumatin from contaminant proteins
      of an homogenate of E. coli in a PEG4000/Phosphate system was used. The data
      shows the effect of the presence and absence of NaCl which was used to carry out
      the extraction of thaumatin into the PEG phase and back into the PO4(-3) phase.
      Simulation results showing the sensitivity to key process parameters, and the
      effect of process variables on performance are presented and discussed. The model
      can be used to predict performance and thus 'robustness' of process conditions as
      well as predict protein recovery yield and purity. This model can also be used to
      implement a suitable control strategy to maintain process stability.

PMID- 1369432
TI  - DNA fingerprinting of the mosquito pathogen Bacillus sphaericus with M13 DNA as a
      probe.
AB  - Hypervariable nucleotide sequences were detected in Bacillus sphaericus by
      hybridization with radioactively labelled M13 DNA. Different serotypes could be
      distinguished by their hybridization profiles. The appearance of bands common for
      mosquito-pathogenic strains and their absence in an apathogenic strain opens the
      probability that M13 could hybridize to specific alleles, related to insect
      toxicity.

PMID- 1369433
TI  - Protein-catalysed protein folding.
AB  - A number of proteins, termed chaperonins, have been identified as part of the
      mechanism of folding other proteins into their biologically active forms. The
      role of chaperonins appears to be twofold--to prevent illegitimate interactions
      with other proteins and to facilitate folding, possibly through an energy
      dependent, catalytic function. Controlled overexpression of chaperonins may be of
      therapeutic value in manipulating human immune response and rescuing certain
      inherited human mutations.

PMID- 1369435
TI  - Effects of nutritional conditions on plasmid stability and production of
      tryptophan synthase by a recombinant Escherichia coli.
AB  - Effects of nutritional conditions and insertion direction of the tryptophan
      synthase (TSase) gene into a plasmid vector on the plasmid stability and the
      production of TSase in high cell concentration cultures were examined using
      recombinant Escherichia coli (E. coli K12 IFO 3301) harboring pBR322trpAB(1) (the
      TSase gene was inserted at the EcoRI site of pBR322 in the clockwise direction)
      and pBR322trpAB(2) (counterclockwise direction). As to the effects of the
      insertion direction, the cells harboring pBR322trpAB(2) were slightly lower in
      the growth rate and the plasmid stability than those harboring pBR322trpAB(1).
      However, the former was higher in the productivity of TSase and the final cell
      concentration attained than the latter. On the other hand, the addition of
      organic nutrients, especially yeast extract, to TK-25 medium was very effective
      to improve the plasmid stability. Among the components of yeast extract, L
      glutamic acid was found to be effective to improve both the plasmid stability and
      the production of TSase. When 1 g/l of L-glutamic acid was added to TK-25 medium,
      a mineral synthetic medium developed for a high concentration culture, 115g (dry
      basis)/l of recombinant cells were obtained in 14 hr and the expression of TSase
      was maintained at 240-300 U/mg-protein during the cultivation.

PMID- 1369434
TI  - Ambruticin S production in amino acid rich media.
AB  - The antimycoticum ambruticin was produced by cultivating the myxobacterium
      Sorangium cellulosum in shake flasks and stirred tank reactors with 10- and 30-l
      working volumes. During growth and product formation amino acid concentrations in
      the complex media were measured by HPLC. In the logarithmic growth phase free
      aspartate and glutamate were assimilated without product formation. After
      consumption of aspartate and glutamate, growth was limited and ambruticin
      production set in. The effects of biological parameters such as age, amount of
      inoculum, pretreatment of cells before inoculation and time of precultivation
      were also investigated.

PMID- 1369436
TI  - Genetic breeding of L-tyrosine producer from Brevibacterium lactofermentum.
AB  - A wild-type parent of Brevibacterium lactofermentum was converted into an L-Tyr
      producer by three steps of genetic breeding. First, acquirement of m-fluoro-D, L
      phenylalanine resistance (1,000 microgram/ml) brought about MF1317 which produced
      3.5 g/l of L-Tyr and a byproduct of 2.8 g/l of L-Phe. Second, increase in the
      drug resistance (5,000 microgram/ml) gave MF358 that produced 6.4 g/l of L-Tyr
      and a byproduct of 6.0 g/l of L-Phe. Third, an L-Phe auxotrophic mutant (FT-1)
      derived from MF358 accumulated 16 g/l of L-Tyr. In FT-1, L-Phe was not
      accumulated at all, but a small amount of anthranilate (0.4 g/l) was. A key
      enzyme in the biosynthesis of L-Tyr, 3-deoxy-D-arabino-heptulosonate-7-phosphate
      synthase, was free from synergistic feedback inhibition by L-Tyr and L-Phe in the
      producers, and so L-Tyr accumulation occurred independently of L-Phe
      concentration in the production medium.

PMID- 1369438
TI  - Biosleuthing with DNA identification.

PMID- 1369437
TI  - Cloning and characterization of genes responsible for m-fluoro-D,L-phenylalanine
      resistance in Brevibacterium lactofermentum.
AB  - Two kinds of 3-deoxy-D-arabino-hepturosonate-7-phosphate (DAHP) synthase genes
      were cloned from an L-Phe-producing mutant of Brevibacterium lactofermentum,
      AJ11957, which was resistant to m-fluoro-D,L-phenylalanine (mFP) and p-fluoro-D,L
      phenylalanine (pFP) and which had DAHP synthase free from feedback inhibition.
      Both genes were cloned using a vector plasmid, pAJ1844, and the resulting
      recombinant plasmids were named pAR1 and pAR2. They had different structures on
      the restriction maps. Both plasmids, pAR1 and pAR2, conferred mFP and pFP
      resistance and L-Phe and L-Tyr productivity on a wild-type strain of B.
      lactofermentum, AJ12036. The degrees of L-Phe-analogue resistance and aromatic
      amino acid productivity of the pAR1-transformant were larger than those of the
      pAR2-transformant. The introduction of pAR1 to AJ12036 resulted in the alteration
      of DAHP synthase activity from a feedback-sensitive mechanism to a feedback
      insensitive one accompanied by an elevated level of specific activity. A DAHP
      synthase deficient mutant of Escherichia coli was complemented by pAR2, but not
      by pAR1. Characteristics of the two kinds of DAHP synthase genes are discussed.

PMID- 1369439
TI  - Characterization of recombinant factor XIIIa produced in Saccharomyces
      cerevisiae.
AB  - Recombinant factor XIIIa (FXIIIa), produced in Saccharomyces cerevisiae, was
      recovered as a fully active cytosolic component and rigorously compared to
      natural F XIIIa from human placenta with respect to physicochemical and
      functional properties. Identical parameters were found in SDS polyacrylamide gel
      electrophoresis, analytical ultracentrifugation and HPLC gel filtration, and all
      spectral characteristics including derivative UV absorbance, fluorescence and
      circular dichroism were identical. Similarly, the interaction of both proteins
      with polyclonal antibodies directed against the entire FXIIIa or its N-terminal 4
      kD activation peptide were identical. Furthermore, thrombin cleavage and fibrin
      cross-linking showed indistinguishable patterns. The only difference we observed
      was with respect to endgroup analysis. The recombinant protein is homogeneous,
      whereas placental FXIIIa shows multiple electrophoretic bands caused by
      microheterogeneity in the C-terminal part of the protein.

PMID- 1369440
TI  - Genotyping of bovine kappa-casein loci following DNA sequence amplification.
AB  - Caseins are a family of milk proteins that exist in several molecular forms
      (alpha s1, alpha s2, beta and kappa) with variant alleles of each. Kappa-caseins
      (kappa-CN) exist as A or B variants and are of particular importance to the
      quality of the milk. We report a rapid non-radioactive method for differentiating
      bovine k-CN alleles. Unlike direct milk protein analysis, this method can be
      utilized for genotyping sperm, or animals of either sex at an early age. A 350bp
      fragment of the bovine kappa-CN gene was amplified by the polymerase chain
      reaction (PCR) technique. The amplified product digested with HinfI endonuclease
      generated restriction fragment length polymorphisms (RFLP's) that allowed precise
      identification of kappa-CN AA, AB or BB genotypes. Hybridization with allele
      specific oligo-probes confirmed the RFLP identification of genotypes. The
      accurate and early identification of milk protein genotypes can have a direct
      impact on dairy cattle breeding strategies.

PMID- 1369441
TI  - Concepts in question regarding HIV infection.

PMID- 1369442
TI  - Animal health and production in the 21st Century. A conference held at Sydney
      University, 9-10 November 1989.

PMID- 1369443
TI  - Commercialization of biotechnology in the Asian region. Report of meeting of
      Asian Productivity Organization (APO) in Osaka, Japan.
AB  - Detailed studies on the commercial development of biotechnology in five countries
      in the Asian Region (viz. Japan, Korea, Taiwan, Thailand, India) indicate a very
      significant role played by government in strategic planning and R & D financing.
      Strong growth is projected in some traditional biotechnology products e.g. amino
      acids such as monosodium glutamate and L-lysine, animal and human vaccines, and
      in environmental applications of biotechnology. The cash flow from these products
      will underpin future development and marketing of diagnostics, anticancer and
      antiviral drugs, particularly in Japan and Korea.

PMID- 1369444
TI  - Genome conference. Lorne, 19-23 February, 1990.

PMID- 1369445
TI  - Molecular and developmental biology of the Cnidaria--basic aspects and
      phylogenetic implications.
AB  - Cnidarians are generally considered to be the most primitive group of
      eumetazoans. They are therefore of considerable interest for comparative studies
      of metazoan development and evolution. The application of molecular techniques to
      cnidarians can provide important insights into developmental processes and
      phylogenetic relationships both within the phylum Cnidaria and among the
      eumetazoa. This paper reviews current knowledge of molecular and developmental
      biology of cinidarians with particular emphasis on tropical scleractinian corals
      and soft corals from the Great Barrier Reef region. Nucleotide sequencing of the
      histone gene cluster has unequivocally established that cnidarians are typical
      eumetazoans. Repeated sequence analysis has been applied to the staghorn corals,
      and implies a major divergence within this group, which corresponds with
      differences in sperm ultrastructure. Recent developmental studies of corals have
      indicated that some species have an unusual method of germ layer formation.
      Molecular events associated with this process, and with other important
      developmental stages, are currently under investigation. Other areas of current
      research interest, including targets for PCR-based investigations into cnidarian
      phylogeny, are highlighted.

PMID- 1369446
TI  - Typing of Legionella pneumophila serogroups 2-14 strains by analysis of
      restriction fragment length polymorphisms.
AB  - A typing method based on analysis of restriction fragment length polymorphisms
      has previously been developed for Legionella pneumophila serogroup 1. Here data
      are presented demonstrating the utility of this method for typing strains of all
      other L. pneumophila serogroups described to date. The method, which is highly
      discriminatory, should be of considerable value in epidemiological investigations
      of legionella infections.

PMID- 1369447
TI  - Chaperonin assisted polypeptide folding and assembly: implications for the
      production of functional proteins in bacteria.
AB  - Production of biologically active foreign proteins with correct three-dimensional
      structures is often difficult in bacteria. Recent advances demonstrate that, for
      some proteins at least, their correct folding and assembly is facilitated by a
      class of proteins known as molecular chaperones. An understanding of the function
      of molecular chaperones may assist in the synthesis in bacteria of functional
      foreign proteins produced by recombinant techniques.

PMID- 1369449
TI  - Capturing the light and capturing the market.

PMID- 1369448
TI  - Amplification of the ZFY and ZFX genes for sex identification in humans, cattle,
      sheep and goats.
AB  - We describe a quick and efficient method of determining the sex of DNA samples
      from humans, cattle, sheep, and goats. Using universal primers we have amplified
      447 or 445 bp fragments from male or female genomic DNA corresponding to the ZFY
      or ZFX genes. Restriction fragment length polymorphism (RFLP) analysis of the
      fragments yielded specific banding patterns between the two sexes in these
      species. Horse, pig and rainbow trout fragments did not show RFLPs with the group
      of enzymes chosen for the other species. Use of this method would allow animal
      breeders to determine the sex of preimplantation embryos before transfer to
      recipient females. Human embryos at risk for sex-linked disorders could be sexed
      soon after in vitro fertilization (IVF) and options considered before
      implantation.

PMID- 1369450
TI  - Proceedings of the XI National Congress of the Italian Cell Culture Association
      (AICC). Rome, Italy, October 29-31, 1990.

PMID- 1369451
TI  - An inducible gene expression system for Neurospora crassa.
AB  - Neurospora crassa acetyl CoA synthetase is highly induced when the growing
      mycelium is transferred from sucrose- to acetate-based medium. The inducible
      promoter of this gene has been isolated and used to control the expression of
      glutamate dehydrogenase. Transformants containing this expression cassette show
      gdh levels up to 25 times higher than the nontransformed host strain. This
      expression cassette will form the basis of a system of heterologous gene
      expression.

PMID- 1369452
TI  - Regulated expression allows high level production and secretion of HIV-1 gp120
      envelope glycoprotein in Drosophila Schneider cells.
AB  - We have established a stable, continuous culture Drosophila Schneider 2 cell line
      that efficiently expresses a secreted, truncated form of the HIV envelope gp120
      protein in a regulated manner. The Drosophila produced recombinant gp120 protein
      is highly glycosylated, is recognized by gp120-specific monoclonal antibodies,
      binds to the CD4 receptor and has the ability to inhibit syncytia formation
      between uninfected CD4+ cells and HIV infected cells. We conclude that this
      recombinant Drosophila envelope protein is an appropriate mimic of the authentic
      viral envelope protein. Thus, the Drosophila cell provides a continuous, stable
      culture system for the efficient expression of secreted forms of complex surface
      glycoproteins in quantities sufficient for detailed analyses.

PMID- 1369453
TI  - Construction of a 7-aminocephalosporanic acid (7ACA) biosynthetic operon and
      direct production of 7ACA in Acremonium chrysogenum.
AB  - We have used cDNA encoding D-amino acid oxidase, and genomic DNA encoding
      cephalosporin acylase from Fusarium solani and Pseudomonas diminuta,
      respectively, to construct a novel hybrid 7-aminocephalosporanic acid (7ACA)
      biosynthetic operon under the control of regulatory elements from the alkaline
      protease gene of Acremonium chrysogenum. Transformants of A. chrysogenum BC2116,
      a high cephalosporin-producing strain, containing this operon, synthesized and
      secreted low levels of 7ACA. Although the amounts are not yet commercially
      significant, this represents the first microbial production of 7ACA and
      demonstrates the feasibility of introducing new biosynthetic capabilities into
      industrial microorganisms by combining fungal and bacterial genes.

PMID- 1369454
TI  - Production of a site specifically cleavable P-glycoprotein-beta-galactosidase
      fusion protein.
AB  - We have fused full length and the carboxyl-half of human MDR1 cDNA with the E.
      coli lacZ gene via a collagen linker and allowed their expression in yeast
      Saccharomyces cerevisiae. Using antibodies against beta-galactosidase we
      partially purified the fusion proteins by immunoprecipitation and show here that
      the full length fusion protein has ATPase activity. By contrast, the fusion
      protein containing the carboxyl-half of P-glycoprotein did not show ATPase
      activity, indicating that both domains of P-glycoprotein are necessary. By
      treatment of the immunoprecipitated fusion protein with collagenase, P
      glycoprotein was released from the beta-galactosidase moiety. The results shown
      here open the possibility for a large scale purification of P-glycoprotein using
      this site specifically cleavable fusion protein.

PMID- 1369456
TI  - Regulatory sequences controlling short chain fatty acid metabolism in Escherichia
      coli.
AB  - Acetoacetate in Escherichia coli is metabolized via the combined enzymatic action
      of a CoA-transferase and a thiolase. Growth of E. coli on short chain fatty acids
      such as butyrate and valerate is also predicated upon the expression of these
      enzymes. The genes for these enzymes (atoDAB) are arranged in an operon and are
      coordinately transcribed in response to the inducer acetoacetate. A positive
      regulatory element, the product of the atoC gene, regulates expression of the
      operon. The atoC gene lies adjacent to the atoDAB operon and all the ato genes
      have been cloned as a single 6.2 kbp restriction fragment (kindly provided by Dr.
      Lauren Sallus Jenkins). We have isolated a series of mutant E. coli strains with
      altered regulatory properties that are either inducible by an alternate
      substrate, or that show constitutive expression of the atoDAB genes. The -10 and 
      35 regions upstream of the atoDAB operon poorly match consensus sequences. In
      addition, the transcriptional start is preceded by a catabolite activator protein
      binding site (CAP site), as well as a putative binding site for the atoC gene
      product as represented by a region of dyad symmetry.

PMID- 1369455
TI  - Expression of the human blood coagulation protein factor XIIIa in Saccharomyces
      cerevisiae: dependence of the expression levels from host-vector systems and
      medium conditions.
AB  - The human blood coagulation protein Factor XIIIa (FXIIIa) was expressed in
      Saccharomyces cerevisiae employing Escherichia coli-yeast shuttle vectors based
      on a 2-mu plasmid. Several factors affecting high production yield of recombinant
      FXIIIa were analysed. The use of the regulatable GAL-CYC1 hybrid promoter
      resulted in higher FXIIIa expression when compared with the constitutive ADCI
      promoter. Screening for suitable yeast strains for expression of FXIIIa under the
      transcriptional control of the GAL-CYC1 hybrid promoter revealed a broad spectrum
      of productivity. No obvious correlation between the expression rate and the
      genetic markers of the strains could be identified. The medium composition
      markedly influenced the FXIIIa expression rates. The expression of FXIIIa was
      strictly regulated by the carbon source. Glucose as the only sugar and energy
      source repressed the synthesis of FXIIIa, whereas addition of galactose induced
      FXIIIa expression. Special feeding schemes resulted in a productivity of up to
      100 mg FXIIIa/l in shake flasks.

PMID- 1369458
TI  - Biotechnology and sustainable development in the Third World.

PMID- 1369457
TI  - Genetic control of flocculation in Escherichia coli.
AB  - Escherichia coli cells form flocs or aggregates by overproducing type 1 pili.
      When the pil operon is placed under the control of a tac or lac promoter-operator
      sequence, the bacterial cells can be induced to form flocs by adding isopropyl
      beta-D-thiogalactopyranoside to the culture medium. This phenomenon of
      genetically induced flocculation can aid in the downstream of biological
      products. This paper describes the construction of two artificially controlled
      plasmids which cause cell flocculation. Cell aggregates 50 microns in mean
      diameter were obtained 1 h after the cells were induced.

PMID- 1369459
TI  - Carbohydrate-based therapeutics.

PMID- 1369460
TI  - Protein secretion in bacteria.
AB  - Most secretory proteins are synthesized as precursors with an amino-terminal
      signal peptide. Genetic identification of proteins essential for signal peptide
      dependent translocation to the Escherichia coli periplasm has led to the
      biochemical dissection of the secretion pathway. Additional mechanisms exist in
      Gram-negative bacteria for protein secretion to the extracellular environment.

PMID- 1369461
TI  - Direct cloning of amplified cDNAs from mRNA.

PMID- 1369462
TI  - Fab assembly and enrichment in a monovalent phage display system.
AB  - We have developed a system that allows the expression of a single copy of an
      antibody Fab molecule on the surface of the filamentous bacteriophage M13 and
      demonstrate the utility of this system for enrichment of specific "Fab phage". A
      "humanized" version of antibody 4D5 (h4D5) directed against the extracellular
      domain of the HER2 (neu) receptor, was used as prototype to assess the assembly
      of Fab molecules on the phage and to determine the power of the enrichment
      system. The h4D5 Fab phage showed specific binding to the extracellular domain of
      the receptor and exhibited an affinity for its antigen virtually identical to the
      Fab itself. By virtue of its antigen binding, the h4D5 Fab phage could be sorted
      from a million-fold excess of non-cognate Fab phage in only two rounds of
      sorting. Further experiments demonstrated that the h4D5 Fab phage could be
      preferentially enriched from mixtures of variant Fab phages that had lower
      affinities for the HER2 receptor.

PMID- 1369463
TI  - Expression of human P-glycoprotein in yeast cells--effects of membrane component
      sterols on the activity of P-glycoprotein.
AB  - A human MDR1 cDNA was introduced into yeast cells. Immunoblot analysis and
      indirect immunostaining showed that some of the P-glycoprotein produced was
      situated in its native orientation in the yeast plasma membrane. Drug-binding
      activities of the recombinant P-glycoproteins were markedly decreased compared to
      that of the authentic P-glycoprotein. To identify the bases of decreased binding
      we studied the effects of membrane component sterols on the azidopine binding and
      found that ergosterol, which is the main sterol in the yeast membrane, and
      calciferol, which is produced from ergosterol by UV irradiation, inhibited
      azidopine binding. These sterols in yeast membrane probably inhibit the function
      of human P-glycoprotein as a multidrug transporter in yeast cells, because
      expression of P-glycoprotein in yeast cells did not confer resistance to
      doxorubicin.

PMID- 1369464
TI  - Taxol. Out of the woods.

PMID- 1369465
TI  - Biocatalysis in the 1990s: a perspective.

PMID- 1369466
TI  - Transgenic animals.

PMID- 1369467
TI  - Molecular basis of multidrug resistance mediated by P-glycoprotein.
AB  - In the past year, our understanding of the biology and molecular basis of
      multidrug resistance of tumours has advanced on several fronts. Intriguing clues
      to some of the key questions in the area provide optimism for future
      understanding and, with luck, eventual prevention and/or treatment.

PMID- 1369468
TI  - The second annual Frederick Conference on Capillary Electrophoresis.

PMID- 1369469
TI  - Gene expression using gram-negative bacteria.

PMID- 1369470
TI  - The Hox gene family in transgenic mice.
AB  - Evidence is accumulating which suggests that the vertebrate Hox homeobox gene
      family plays an important role in pattern formation, particularly in the
      specification of regional diversity. In the last year important advances in the
      understanding of their regulation and function have been provided using
      transgenic mice.

PMID- 1369471
TI  - Use of colony-stimulating factors in combination with high-dose chemotherapy.
AB  - Recent clinical trials of two hematopoietic cytokines, granulocyte- and
      granulocyte-macrophage colony stimulating factors, in combination with
      chemotherapy, have shown that they allow substantially higher doses of
      chemotherapeutic agents to be used. Administering cytokines decreased the length
      of time for granulocyte recovery, the incidence of infection, the need for
      antibiotics, as well as shortening the duration of hospitalizations. Current work
      is focusing on the use of cytokines to stimulate circulating progenitor cells for
      pheresis and replacement. There are still striking gaps, however, in our
      knowledge of the interactions of the various cytokines with each other and with
      chemotherapeutic agents.

PMID- 1369472
TI  - Biotechnology and the Third Review Conference of the Biological and Toxin Weapons
      Convention.

PMID- 1369473
TI  - Forensic applications.
AB  - The introduction of DNA based identity testing has revolutionized the field of
      forensic analysis of biological materials. Most of the publications during the
      past year expand earlier studies that began more than seven years ago, on the
      properties of DNA recovered from different types of evidential materials; these
      studies examine the suitability of these samples for identity testing, the effect
      of different environmental insults the population genetics of loci used for
      identity testing, and the methods used for statistical analysis of the DNA
      patterns.

PMID- 1369474
TI  - Conquering multidrug resistance in cancer chemotherapy.

PMID- 1369475
TI  - DnaK-mediated alterations in human growth hormone protein inclusion bodies.
AB  - Protein overproduction in microbes frequently results in protein misfolding and
      aggregation though the molecular basis for this process is unclear. The HSP70
      chaperonin, DnaK, was identified as an important factor controlling heterologous
      protein aggregation in Escherichia coli. Co-overproduction of DnaK significantly
      reduced human growth hormone (HGH) protein inclusion body formation and the
      extent of HGH aggregation.

PMID- 1369476
TI  - HPCE '92.

PMID- 1369477
TI  - High-level expression of a recombinant antibody from myeloma cells using a
      glutamine synthetase gene as an amplifiable selectable marker.
AB  - We report a method for introducing a glutamine synthetase (GS) selectable marker
      into myeloma cells in which transfectants are selected by growth in a glutamine
      free medium. Vector amplification can subsequently be selected using the specific
      inhibitor of GS, methionine sulphoximine (MSX). Using this system, DNA sequences
      encoding a chimeric B72.3 IgG4 antibody were expressed from hCMV-MIE promoters in
      NSO myeloma cells. A cell line was isolated after a single round of selection for
      vector amplification which contains approximately 4 copies of the vector,
      secretes 10-15 pg/cell/day cB72.3 antibody during exponential growth and can
      accumulate 560 mg/l antibody in a fed-batch air-lift fermentation system.
      Productivity is stable in the absence of MSX selection.

PMID- 1369478
TI  - Bauhaus biology: biotechnology and the common cold.

PMID- 1369479
TI  - The DNA sequence of gamma-glutamyltranspeptidase gene of Bacillus subtilis
      (natto) plasmid pUH1.
AB  - The gamma-glutamyltranspeptidase (gamma-GTP) gene of Bacillus subtilis (natto)
      plasmid designated pUH1, which is responsible for polyglutamate production, has
      been cloned and the nucleotide sequence determined. The sequence contains a
      single open-reading frame stretching for 1260 bp with a relative molecular mass
      of 49,356. Putative -35 and -10 sequences, TTCAAA and TATTAT, were observed as
      the consensus sequence for the promoter recognized by the sigma 43 RNA polymerase
      of B. subtilis, and the ribosome binding site, the sequence of which was AACGAG,
      was complementary to the binding sequence of B. subtilis 16S rRNA except for one
      base. The amino acid sequence of the gene with the segment of putative protein
      C403 of staphylococcal plasmid pE194 indicates homology, whereas that with
      Escherichia coli and mammalian gamma-GTPs does not show any similarity at all.

PMID- 1369481
TI  - Restriction fragment length polymorphisms of mitochondrial DNAs from the
      basidiomycetes Pleurotus species.

PMID- 1369480
TI  - Sex determination of bovine embryos by restriction fragment polymorphisms of PCR
      amplified ZFX/ZFY loci.

PMID- 1369482
TI  - Function and evolution of secondary metabolites--no easy answers.

PMID- 1369483
TI  - Molecular design and catalytic function of a B12-enzyme mimetic.
AB  - Developing artificial holoenzymes requires attention to the molecular design, not
      only of the active site, but also of its microenvironment, which in the naturally
      occurring enzyme is provided by the apoprotein. Microenvironmental effects play a
      major role in determining the catalytic performance of an enzyme. Using the
      development of a B12-dependent holoenzyme mimetic as an example, the important
      factors and concepts underlying the approaches to developing an artificial
      holoenzyme are discussed.

PMID- 1369484
TI  - Overexpression and purification of asparagine synthetase from Escherichia coli.
AB  - Overexpression of the asnA gene from Escherichia coli K-12 coding for asparagine
      synthetase (EC 6.3.1.1) was achieved with a plasmid, pUNAd37, a derivative of
      pUC18, in E. coli. The plasmid was constructed by optimizing a DNA sequence
      between the promoter and the ribosome binding region. The enzyme, comprising ca.
      15% of the total soluble protein in the E. coli cell, was readily purified to
      apparent homogeneity by DEAE-Cellulofine and Blue-Cellulofine column
      chromatographies. The amino-terminal sequence, amino acid composition, and
      molecular weight of the purified protein agreed with the predicted values based
      on the DNA sequence of the gene. Furthermore the native molecular weight measured
      by gel filtration confirmed that asparagine synthetase exists as a dimer of
      identical subunits.

PMID- 1369486
TI  - Chiral chromatography: highlights from a 1991 EAS symposium.

PMID- 1369485
TI  - Catalytic properties of X-prolyl dipeptidyl aminopeptidase from Lactococcus
      lactis subsp. cremoris nTR.
AB  - An X-prolyl dipeptidyl aminopeptidase (X-PDAP; EC 3.4.14.5) was identified to be
      loosely bound on the inner cell membrane fraction of Lactococcus lactis subsp.
      cremoris nTR. The biosynthesis of X-PDAP was continuously increased before the
      late-log growth phase of the bacteria. Both Gly-Pro-pNA and Ala-Ala-pNA were
      hydrolyzed by X-PDAP; the kcat/Km value of the former was about 10-fold that of
      the latter. The Ki of X-Pro and Pro-X were more specific to X-PDAP than those of
      X-Ala. The enzyme splitting a dipeptide sequentially from beta-casomorphin as a
      model catalytic pattern was identified and some properties of the enzyme were
      further characterized.

PMID- 1369487
TI  - Construction, bacterial expression and characterization of a bifunctional single
      chain antibody-phosphatase fusion protein targeted to the human erbB-2 receptor.
AB  - We have constructed genes expressing single-chain antigen binding proteins (scFv)
      which recognize the human erbB-2 receptor. These genes encode the heavy and light
      chain variable domains of an erbB-2 receptor specific monoclonal antibody, MAb
      FRP5, connected by a peptide linker. In order to express a bifunctional molecule,
      a bacterial alkaline phosphatase gene was fused 3' to the scFv gene. The
      scFv(FRP5) and scFv(FRP5)-alkaline phosphatase fusion protein (scFv(FRP5)-PhoA)
      expressed in E. coli specifically recognize the human erbB-2 protein and compete
      with MAb FRP5 for binding to the receptor. The bound scFv(FRP5)-PhoA protein can
      be detected directly on tumor cells using a substrate for alkaline phosphatase,
      showing that the chimeric protein retains both binding and enzymatic activity.

PMID- 1369488
TI  - Enzyme immobilization on ion exchangers by forming an enzyme coating with
      transglutaminase as a crosslinker.

PMID- 1369489
TI  - Fatty acid alteration by a delta 9 desaturase in transgenic tobacco tissue.
AB  - Nicotiana tabacum tissue was transformed with a rat stearyl-CoA desaturase gene.
      Gas chromatographic analysis showed an increase in monounsaturated 16 and 18
      carbon fatty acids in selected transformed calli and leaves. Fractionation of
      lipid classes indicated that palmitoleic acid was found in the
      phosphatidylcholine fraction of desaturase-transformed leaves, but not in leaves
      transformed with vector sequences. Plant transformation was verified by
      polymerase chain reaction (PCR) amplification of total leaf DNA.

PMID- 1369490
TI  - Renaturation of a single-chain immunotoxin facilitated by chaperones and protein
      disulfide isomerase.
AB  - B3(Fv)-PE38KDEL, a recombinant immunotoxin, forms inclusion bodies when produced
      in Escherichia coli. In renaturation experiments, nonspecific aggregation of non
      native polypeptide chains, and the formation of incorrect disulfide linkages lead
      to inactive molecules. To prevent these side reactions, we added molecular
      chaperones and protein disulfide isomerase (PDI) to the refolding buffer. Both
      DnaK and GroEL/S influenced the reactivation process. GroEL alone inhibited
      reactivation, but in the presence of ATP, GroEL and GroES significantly increased
      the yield of active protein. DnaK also increased the yield of properly folded
      protein and the stimulating effect of DnaK was also observed using immobilized
      DnaK, which can be used repeatedly without significant loss of activity. PDI,
      which catalyzes disulfide bridging of proteins, also stimulated reactivation of
      the immunotoxin. Under optimum conditions, reactivation yields in the presence of
      PDI were about twice that obtained with nonenzymatic disulfide bond formation.
      Furthermore, DnaK and PDI were additive when renaturation was performed in the
      presence of both proteins.

PMID- 1369492
TI  - Purification and characterization of benzoyl-CoA ligase from a syntrophic,
      benzoate-degrading, anaerobic mixed culture.
AB  - The benzoyl-CoA ligase from an anaerobic syntrophic culture was purified to
      homogeneity. It had a molecular mass of around 420 kDa and consisted of seven or
      eight subunits of 58 kDa. The temperature optimum was 37-40 degrees C, the
      optimum pH around 8.0 and optimal activity required 50-100 mM TRIS-HCl buffer, pH
      8.0 and 3-7 mM MgCl2; MgCl2 in excess of 10 mM was inhibitory. The activation
      energy for benzoate was 11.3 kcal/mol. Although growth occurred only with
      benzoate as a carbon source, the benzoyl-coenzyme A (CoA) ligase formed benzoyl
      CoA esters with benzoate, 2-, 3- and 4-fluorobenzoate, picolinate, nicotinate and
      isonicotinate. Acetate was activated to acetyl-CoA by an acetyl-CoA synthetase.
      The Km values for benzoate, 2-, 3- and 4-fluorobenzoate were 0.04, 0.28, 1.48 and
      0.32 mM, the Vmax values 1.05, 1.0, 0.7 and 0.98 units (U)/mg, respectively. For
      reduced CoA (CoA-SH) a Km of 0.07 mM and a Vmax of 1.05 U/mg and for ATP a Km of
      0.16 mM and a Vmax of 1.08 U/mg was determined. Benzoate activation was inhibited
      by more than 6 mM ATP, presumably by pyrophosphate generation from ATP. The
      inhibition constant (Ki) for pyrophosphate was 5.7 mM. No homology of the N
      terminal amino acid sequence with that of a 2-aminobenzoyl-CoA ligase of a
      denitrifying Pseudomonas sp. was found.

PMID- 1369491
TI  - Enzymatic preparation of 1,6-anhydro-muropeptides by immobilized murein
      hydrolases from Escherichia coli fused to staphylococcal protein A.
AB  - In order to produce biologically active 1,6-anhydro-muropeptides in large amounts
      by enzymatic degradation of isolated bacterial murein polymer highly specific
      periplasmic murein-metabolizing enzymes from Escherichia coli are made available.
      The genes slt, dacB, and mepA, encoding the soluble lytic transglycosylase (Slt),
      the penicillin-sensitive DD-endopeptidase (PBP4), and the penicillin-insensitive
      murein endopeptidase A (MepA), were independently fused to the N-terminal
      encoding sequence of staphylococcal protein A (SpA) under control of the
      temperature-inducible phage lambda pR promoter. The SpA fusion proteins were
      stably over-produced at high levels in E. coli upon temperature induction at 42
      degrees C and account for 3% (5 mg SpASlt/l culture), 3% (5 mg SpAPBP4/l
      culture), and 0.3% (0.5 mg SpAMepA/l culture) of total protein. The SpA fusion
      proteins, immobilized on IgG Sepharose, are proteolytically sensitive, in vitro,
      resulting in complete degradation of the SpA portion of the fusion proteins and
      release of the murein hydrolases in intact and enzymatically active form into the
      supernatant. Proteolytic degradation could be prevented by p
      hydroxymercuribenzoic acid (PHMB) or ethylenediaminetetraacetate (EDTA)
      suggesting the involvement of the periplasmic protease Pi from E. coli. The
      immobilized fusion proteins were enzymatically active and could be used for the
      batch production of biologically active 1,6-anhydro-muropeptides, which were
      successively separated on HPLC. Isolated murein polymer was degraded
      quantitatively to monomeric 1,6-anhydro-muropeptides when immunoglobulin G (IgG)
      SpASlt was used in combination with IgG-SpAMepA. A combination of IgG-SpASlt with
      IgG-SpAPBP4 left the 1,6-anhydro-dimers and oligomers being cross-linked via an
      LD-peptide bond (m-DAP-m-DAP) uncleaved.

PMID- 1369493
TI  - Regulating gene expression in transgenic animals.
AB  - Regardless of the field of application, the raison d'etre of transgenic animals
      is to study gene regulation and function. With increasing frequency, mammalian
      genes are being isolated with no concomitant knowledge of their function. The
      human genome mapping initiative will undoubtedly produce a cornucopia of such
      genes. While the merit of taking a transgenic route to study genes of unknown
      function is axiomatic, the choices of strategies for gene regulation in vivo may
      not be fully appreciated. This review will address two main points: first, the
      targeted and regulated expression of genes, and second, the structural and
      functional ablation of genes.

PMID- 1369494
TI  - Isolation and characterization of the groES and groEL genes of Bacillus subtilis
      Marburg.
AB  - The complete set of groES and groEL gene homologues from Bacillus subtilis
      Marburg 168 was identified, cloned, and characterized. The nucleotide sequence
      indicated the presence of two open reading frames corresponding to the groES and
      groEL genes. The presumptive GroES and GroEL proteins were calculated to be
      polypeptides of 10,175 and 57,175 Da, respectively, and showed extensive sequence
      similarities with the known GroES and GroEL proteins of Escherichia coli and
      Mycobacterium tuberculosis. A heat-inducible transcript initiated upstream of the
      groES coding region was identified by primer-extension analysis of in vivo
      transcripts, indicating that the two genes consist of an operon. At least six
      heat-shock inducible proteins were identified in the cell extract of heat treated
      B. subtilis. Two proteins of 10 and 60 kDa overproduced in B. subtilis cells
      carrying a multi-copy groES and groEL plasmid were demonstrated to correspond to
      two out of the six heat-shock inducible proteins. The groES and groEL genes of B.
      subtilis were physically mapped on the 60 degrees region of a 360 degrees map and
      genetically mapped at the position of 40% linkage with the purB locus using PBS1
      transduction of the groEL genes tagged with a chloramphenicol resistance (chlr)
      marker.

PMID- 1369495
TI  - Stimulative effect of non-parenchymal liver cells on ability of tyrosine
      aminotransferase induction in hepatocytes.
AB  - Hepatocytes and non-parenchymal liver cells were isolated from adult rat liver
      and co-cultured for 48 hours as a monolayer on polystyrene culture dishes. The
      ability of tyrosine aminotransferase (TAT) induction in hepatocytes was examined
      in the presence of dexamethasone and dibutyryl cAMP. Non-parenchymal cells
      greatly enhance the ability of TAT induction of hepatocytes. A soluble factor
      with molecular weight of more than 10,000 is responsible for this enhancement,
      because conditioned medium prepared from non-parenchymal cells is also
      stimulatory. Non-parenchymal cells restored the ability in hepatocytes damaged
      with the addition of D-galactosamine. Conditioned medium prepared from non
      parenchymal cells treated with D-galactosamine had higher activity of enhancement
      than the medium from normal cells. The soluble factor might be released in
      response to some signal of injury. Hepatocytes and non-parenchymal cells were
      immobilized within Ca-alginate, and although immobilized hepatocytes rapidly lost
      the ability to induce TAT, hepatocytes co-immobilized with non-parenchymal cells
      maintained the ability during 4 days of culture. These results indicated that non
      parenchymal liver cells, as well as hepatocytes, could be used to construct a
      bioartificial liver support system.

PMID- 1369496
TI  - Cell Culture Engineering III. Conference proceedings. Florida, February 1-7,
      1992.

PMID- 1369497
TI  - Process development for the production of recombinant antibodies using the
      glutamine synthetase (GS) system.

PMID- 1369498
TI  - Demonstration of exopolysaccharide production by enterohemorrhagic Escherichia
      coli.
AB  - Enterohemorrhagic Escherichia coli O157:H7 produces visibly slimy colonies when
      grown on Sorbitol/MacConkey or Maloney's agar plates at room temperature,
      indicative of exopolysaccharide (EPS) production. Eighteen of 27 (67%) wild-type
      E. coli O157:H7 isolates produced enough EPS to be visually distinguishable. Of
      five strains that showed no visible EPS production on these media, four (80%) did
      produce slimy colonies on media containing higher salt concentrations.
      Measurements of EPS production by colorimetric determination of uronic acid
      indicated that EPS production was affected by growth temperature, atmosphere, and
      medium. Wild-type E. coli O157:H7 strain 932 produced the greatest amounts of EPS
      when grown anaerobically at 37 degrees C, whereas its plasmid-cured derivative
      932P produced large quantities of EPS when grown aerobically at room temperature.
      Electron micrographs revealed thin, flexible fibers extending from the bacterial
      cell surface. Cells of strain 932P grown aerobically at room temperature were
      completely encased in a thick EPS matrix. Chemical analysis of purified EPS
      revealed that it is very similar or identical to colanic acid. E. coli O157:H7
      adheres better to INT 407 cells when grown under conditions that favor high EPS
      production than when grown under conditions that repress EPS production.

PMID- 1369499
TI  - Hemagglutination (fimbriae) and hydrophobicity in adherence of Serratia
      marcescens to urinary tract epithelium and contact lenses.
AB  - The capacity of 59 isolates of Serratia marcescens, obtained from urinary tract
      infections, wounds, and contact lenses or their paraphernalia, to agglutinate
      erythrocytes from different animal species was tested. Three main patterns were
      found: mannose-sensitive agglutination of guinea-pig, fowl or horse erythrocyte;
      mannose-resistant agglutination of chicken or pigeon erythrocytes alone or in
      combination with mannose-sensitive agglutination; and no agglutination.
      Hemagglutination capacity was associated with isolates from urinary tract
      infection, but not with isolates associated with contact lenses. Adherence to
      human urinary tract epithelium did not correlate with the hemagglutination
      patterns nor with the origin of the isolates. Some strains of different
      hemagglutination pattern were selected for the study of hydrophobicity and
      adherence to contact lens polymers. Hydrophobicity, as determined by degree of
      partition in hexadecane and water (BATH-values), correlated neither with degree
      of adherence to contact lens polymers nor with the hemagglutination pattern. For
      a representative strain there was an excellent correlation (r2 = 0.98) between
      adherence and the water content (hydrophobicity) of the lens polymers. These
      results suggest that, as with tissues, other factors interact with hydrophobicity
      in causing adherence to plastics.

PMID- 1369500
TI  - Restriction polymorphisms in the internal transcribed spacers and 5.8S rDNA of
      Saccharomyces.
AB  - Polymorphisms in enzymatically amplified ribosomal DNA (rDNA) were examined in 18
      strains of Saccharomyces. Restriction patterns generated from the region spanning
      the internal transcribed spacers (ITS) and the 5.8S rDNA produced two clusters
      corresponding to S. bayanus and S. cerevisiae. The type culture of S.
      carlsbergensis (ATCC 76529), which could not be separated from the S. cerevisiae
      group by small subunit (SSU) rDNA patterns, showed a ScrfI profile that was
      distinct from all the other strains. The type culture of S. intermedius var.
      turicensis (ATCC 76519) is assigned to S. bayanus on the basis of the combined
      results of SSU and ITS restriction analyses. S. kluyveri occurred at a separate
      branch of the distance tree and is unrelated to any of the strains. Results were
      in general agreement with reported DNA homologies and are discussed in relation
      to other molecular and genetic data.

PMID- 1369501
TI  - Cell culture of Taxus as a source of the antineoplastic drug taxol and related
      taxanes.
AB  - Callus cultures of Taxus cuspidata and Taxus canadensis were induced using
      different tissue explants including green and red arils, seed contents, young
      stems and needles. Callus derived from stem segments displayed the best growth in
      defined media. The culture medium was supplemented with reducing agents and
      phenolic-binding compounds to inhibit callus darkening and subsequent growth
      reduction. T. cuspidata explant growth was affected by different concentrations
      and ratios of 2,4-D and kinetin. Callus tissues of T. cuspidata were extracted
      for taxol after 2 months in culture and analysed by HPLC. The presence of taxol
      (0.020 +/- 0.005% of the extracted dry weight) was indicated based on retention
      time, U.V. spectra, peak purity as assessed by photo-diode array spectroscopy and
      compared with an authentic taxol standard, as well as by 1H-NMR analysis.
      Suspension cultures of T. cuspidata were established from the callus cultures,
      subsequently immobilized onto glass fiber mats, and maintained as immobilized
      cultures for 6 months. The immobilized cell cultures also produced taxol at
      levels up to 0.012 +/- 0.007% of the extracted dry weight.

PMID- 1369502
TI  - Developments in health services research: perspectives from Britain and the
      United States.

PMID- 1369503
TI  - [Pulmonary small cell carcinoma: late sequelae in long-term survivors].
AB  - BACKGROUND: To assess the long term survivors rate and its complications in a
      group of patients diagnosed of small cell lung cancer. METHODS: Clinical records
      of 227 patients diagnosed of small cell lung cancer over a period of ten years
      have been retrospectively reviewed. Global survival, survival free of disease,
      type of therapy, and complications developed after the initial diagnosis have
      been analyzed in patients surviving two or more years after the initial diagnosis
      of small cell lung cancer. RESULTS: Global survival has been of 7% at two years
      and 2% at five years. Three patients (19%) reached the two years survival with
      active disease. Other three patients developed late relapses after a minimum
      follow up of two years free of disease. 19% of survivors suffered a second
      neoplasm. 31% developed signs and symptoms of lung fibrosis. A patient (6%)
      developed ischemic cardiopathy and another one presented a neurologic picture
      consisting in progressive neurologic changes and dementia that could not be
      attributed to his initial disease. CONCLUSIONS: Long term survival in small cell
      lung cancer is still a relatively rare event however the potential complications
      for these patients are significant. Balance between benefit of therapy and its
      toxicity must be optimized.

PMID- 1369504
TI  - [Incidental discovery of adrenal masses through diagnostic imaging].

PMID- 1369505
TI  - Effect of digoxin on experimental adrenaline-induced hyperglycemia and insulin
      induced hypoglycemia.
AB  - The effect of digoxin (0.035 mg/kg b.w., i.v.) on adrenaline-induced
      hyperglycemia (adrenaline: 50 micrograms/kg b.w., s.c.) and on insulin-induced
      hypoglycemia (insulin: 0.4 mU/kg b.w., s.c.) was studied in experiments on
      rabbits. Digoxin intensified the adrenaline-induced hyperglycemia at the 30th and
      60th minutes of application. The hyperglycemia in this case subsided more
      rapidly. Digoxin alone caused on elevation of the blood sugar levels that was
      most pronounced at the 30th minute of introduction. These elevated levels fell to
      the initial value by the 180th minute. The blood sugar levels in the rabbits
      treated with physiological solution rose slightly. This was most noticeable at
      the 120th minute. Digoxin attenuated the insulin-induced hypoglycemia
      significantly at the 120th, 150th, and 180th minutes (p < 0.05). We suggest that
      the increase of the adrenaline-induced hyperglycemia and the attenuation of the
      insulin-induced hypoglycemia could be linked to the release of catecholamines in
      the acute stage of the action of Digitalis glycosides.

PMID- 1369506
TI  - Elastoid transformation of the collagen fibrils in scleroderma skin.
AB  - Electron microscope study was conducted on bioptic material taken from the skin
      of 20 scleroderma patients (15 with progressive scleroderma and five with
      circumscribed scleroderma). In all cases, we observed elastoid transformation of
      the collagen fibrils. This phenomenon has a focal character and can be formed
      either directly or indirectly. The direct elastoid transformation is a result of
      aggregation of superficially damaged collagen fibrils. In such cases the elastoid
      acquires a fibrous structure. The indirect elastoid transformation is preceded by
      the complete destruction of the collagen fibrils. The fibrous elastoid is
      considered to be a pathologic form of fibrogenesis in scleroderma.

PMID- 1369507
TI  - Physical and intellectual development in children with congenital hypothyroidism.
AB  - Twenty four patients (14 girls and 10 boys aged six months to 23 years) with
      congenital hypothyroidism were studied. The diagnoses of all subjects were made
      15 days to one year after birth. After being diagnosed, each child was started
      immediately on replacement hormonotherapy. Parameters of their physical and
      mental development were analyzed depending on the type of thyroid disorder,
      patient age at the beginning of treatment and the adequacy of treatment. These
      parameters were within the normal limits for 71 percent of the patients. However,
      the remaining 29 percent of the patients were mentally retarded. The authors'
      assumption is that the lower intellectual parameters for these patients were
      primarily a result of delayed diagnoses and irregularly conducted treatments in
      household surroundings.

PMID- 1369508
TI  - Therapeutic effect of the laser system Prometeus in the treatment of
      vertebrogenic lumboradiculalgia.
AB  - The authors report their experience in the application of laser therapy using 904
      nm laser irradiation and impulse power of 10 W on patients with vertebrogenic
      lumboradiculalgia (osteochondrosis and herniation of the intervertebral disk).
      The therapeutic effect of the PROMETEUS type laser system is compared to that of
      similar equipment reported in literature. Pain was usually relieved between days
      five and 10 of laser therapy, or, in cases of slower convalescence, by day 15.
      Clinical symptoms of the disorders also disappeared simultaneously with the
      alleviation of pain. Our results are similar to those obtained by A.S. Krjuk
      (1986) and S. Gatev (1985), better than those of Van Lyancin (1988) and worse
      than those of D. Milani (1987). Laser therapy produces no side effects. It is an
      important contribution to the armamentarium of modern physiotherapeutic methods.
      When it is administered properly, it is painless, aseptic and does not cause
      trauma or allergic reactions. Moreover, it reduces the usage of drugs and
      consumable materials.

PMID- 1369509
TI  - Suppression of experimental barbiturate and phenytoin withdrawal syndrome using
      valproate sodium.
AB  - A neuropharmacological study was performed to investigate the effect of valproate
      sodium (VS) used to suppress the barbiturate and phenytoin withdrawal syndrome
      induced experimentally in 1152 male Wistar rats. Valproate sodium was
      administered by mouth according to the following protocol: initial bolus dose of
      400 mg/kg b.w. followed eight hours later by the first maintaining dose of 50
      mg/kg b.w. This was given every 12 hours for five days. VS plasma levels were
      determined by gas chromatography. The therapeutic effect of valproate sodium was
      assessed by the seizure reactivity of the experimental and the control animals to
      an electroshock (50 mA/0.1 sec.). The results strongly indicate that valproate
      sodium inhibits the experimentally induced barbiturate and phenytoin withdrawal
      syndrome without causing drug dependance. It is suggested that some of the
      valproate sodium metabolites possess antiwithdrawal effect.

PMID- 1369510
TI  - DNA-analysis of patients with autosomal dominant polycystic kidney disease.
AB  - Indirect DNA analysis was performed on 12 families totalling 80 people. The
      analysis used five genetic markers flanking the gene: 3'HVR, pGGG, 218 EP6, 24-1,
      26-6. In 11 of the families (92%), a linkage with the PKD1 gene in chromosome 16
      was established. In one family, the disease did not segregate with the
      polymorphic markers of PKD1-locus, thus excluding any possibility that a mutation
      in this locus was the cause of the autosomal dominant polycystic kidney disease
      (ADPKD). A correlation was discovered between the positive echographic diagnosis
      and the genotype in the PKD1-dependent patients with ADPKD. In 28.6 percent of
      the children studied, and in 12.5 percent of subjects under the age of 30, the
      echographic diagnosis was corrected through DNA analysis.

PMID- 1369511
TI  - Computer tomographic densohistogramic characteristic of the renal cortex in
      children with suspected autosomal dominant polycystic kidney disease.
AB  - Computertomographic densohistogramic analysis of the renal cortex was performed
      on 36 children aged seven to 19. The clinicogenealogical and echographic findings
      suggest the presence of autosomal dominant polycystic kidney disease (ADPKD).
      Diagnoses made on the basis of two methods (echography and computer tomography)
      coincided in only 46.15 percent of examined cases. Histogramic analysis confirmed
      the echographic diagnosis of ADPKD in 38.46 percent of the remaining cases while
      it rejected the ADPKD diagnosis in 15.39 percent. Computer tomographic
      densohistogramic analysis is recommended for children when echographic findings
      suggest the presence of ADPKD. It allows early detection of the disease,
      effective medical surveillance and prophylaxis of complications.

PMID- 1369512
TI  - Digital subtraction angiography in renal tumours.
AB  - By their nature, more than 98 percent of renal tumours are malignant. Clinically,
      early symptoms of malignancy are difficult to detect. Because of this, treatment
      of tumorous formations in the kidneys still is unsatisfactory. In general
      diagnostic terms, angiographic study can play an important role as a preoperative
      method that more accurately defines the degree of the spread of cancer as well as
      the extent of renal vessel involvement in this process. The authors report their
      experience in performing digital subtraction angiography (DSA) in 39 patients
      with renal tumours. The advantages of the method are emphasized by a comparison
      of 38 intra-arterial digital subtraction renal vasographic studies and 11
      cavographic studies with respect to reduced irradiation doses and contrast
      material. In addition, the method allows qualitative image processing and the
      performance of therapeutic procedures such as embolization, which was done in 17
      patients.

PMID- 1369514
TI  - Arteriovenous aneurysms in patients on hemodialysis.
AB  - Realization of vascular access for patients with chronic renal failure on chronic
      hemodialysis sometimes proves to be a difficult task. Problems arise when these
      routes start creating complications and technical difficulties after longterm
      hemodialysis. A similar problem arises in dealing with arteriovenous aneurysms in
      patients on chronic hemodialysis. Along with technical difficulties, there also
      are a number of problems related to hemodynamics and hemostasis. In the present
      study, 32 patients were analyzed. These patients had advanced arteriovenous
      aneurysmal dilatations which necessitated surgical intervention. The state of
      advancement, the causes and the possible types of aneurysms were taken into
      account. Serious surgical aneurysmal complications were observed in more than 40
      percent of the cases. After surgical removal of the arteriovenous aneurysms, the
      problem of creating new routes for continuing hemodialysis always arose and
      frequently led to atypical and nonconventional solutions. Suggestions are made
      for prolongation of life and maximal avoidance of aneurysmal dilatation
      development in the vascular accesses of patients on chronic hemodialysis.

PMID- 1369513
TI  - Ionized calcium in patients with chronic renal failure.
AB  - Parameters of various renal disorders were studied in 31 patients (17 men and 14
      women) who all were in the stage of chronic renal failure (CRF). These parameters
      included total serum creatinine, ionized calcium, serum creatinine, creatinine
      clearance and acid-base balance. The results were compared with a control group
      of 30 healthy subjects. In the patients with first stage CRF, the total serum
      calcium did not significantly decrease (mean = 2.19 +/- 0.12 mmol/l) and ionized
      calcium was within reference value limits (mean = 1.28 +/- 0.02 mmol/l). The
      percentage of ionized calcium in total serum calcium was higher for these
      patients (mean = 58.43%) than for the control group (mean = 52.25%). For patients
      with first and second stage CRF, the total serum was significantly lower (mean =
      1.92 +/- 0.03 mmol/l) than for the healthy controls (p < 0.001) as well as for
      patients with first stage CRF (p < 0.05). The ionized calcium in these patients
      was not significantly lower (mean = 1.14 +/- 0.01 mmol/l); however, its
      percentage was higher than that of serum calcium (mean = 59.38%). There was a
      slight negative correlation between the levels of ionized calcium and serum
      creatinine in patients with first stage CRF (r = -0.30) and a significant
      correlation in patients with second and third stage CRF.

PMID- 1369515
TI  - A case of xanthogranulomatous pyelonephritis successfully treated operatively.

PMID- 1369516
TI  - Ultrastructural changes of cutaneous nerves in scleroderma.
AB  - Ultrastructural changes in cutaneous nerves of 38 patients with progressive
      scleroderma and eight patients with circumscribed scleroderma are described in
      the present study. Changes in the myelinated as well as in the unmyelinated
      fibers were observed in all cases. Myelinated fibers exhibited progressive
      disintegration of their myelin sheaths. Edema of the cytoplasm and various
      lesions of the organelles were observed in the Schwann cells. The basal membranes
      of both myelinated and unmyelinated fibers were irregularly thickened and flimsy
      in appearance. The axis cylinders were affected to a lesser extent. Edema of the
      axoplasm, and, less often, reduction of the number of neurofibrils and
      microtubules were observed there. Sometimes, the nerve fibers were enwrapped
      compactly by a considerable amount of collagen fibrils. The observed changes of
      the peripheral skin nerves are very often secondary. They are the morphologic
      basis of a limited or generalized neuropathy which sometimes develops.

PMID- 1369517
TI  - Epidemiological study of the frequency of prescribing antiepileptic drugs.
AB  - This epidemiological study reviewed the frequency of prescribing antiepileptic
      drugs for the period 1982 to 1991 in four regions of Bulgaria. The study included
      8,340 outpatients with epilepsy. The therapeutic approaches to primary
      generalized, focal, and secondary types of epilepsy were evaluated. The drug of
      preference in all types of epilepsy was found to be phenobarbital (26.3 to
      37.8%), followed by carbamazepine (14.0 to 29.8%), bellonal, sacerno, phenytoin,
      etc. Valproate was prescribed only in a few cases (0 to 2.1%). Combinations of
      phenobarbital anc carbamazepine prevailed in the therapeutic approach to
      epilepsy. The share of polytherapy in the treatment of epilepsy tended to
      decrease in favour of monotherapy. The data on the antiepileptic drug utilization
      given in the present study are calculated in the internationally accepted unit, a
      daily defined dose.

PMID- 1369518
TI  - A comparison of surgical training with live anesthetized dogs and cadavers.
AB  - Cadavers were compared with live anesthetized dogs for their effectiveness as
      models for surgical training of veterinary medical students. One group of
      students was trained using cadavers, and a peer group was trained using live
      anesthetized dogs. Both groups then performed an intestinal anastomosis using a
      live subject. The time to completion of the procedure was recorded. The
      anastomoses and celiotomy closures were evaluated. Each anastomosis was isolated
      and pressure tested. Reviewers blindly scored each surgical team's performance
      based on actual inspection of the surgical site and on viewing videotapes of the
      procedure. The participants' attitudes toward the use of live animals in teaching
      and research were documented before and after training. No statistically
      significant differences could be detected between the two groups. The results
      suggest that some substitution of cadavers for live dogs in surgical training
      might be feasible.

PMID- 1369519
TI  - Abdominal wall reconstruction with a vascular external abdominal oblique
      myofascial flap.
AB  - A myofascial island flap for abdominal wall reconstruction was based on the
      lumbar component of the external abdominal oblique muscle and supplied by a major
      neurovascular pedicle consisting of branches of the cranial abdominal artery,
      cranial hypogastric nerve, and a satellite vein. The flap was elevated and
      sutured into a 10 cm x 10 cm body wall defect in five dogs. The dogs were
      observed for 26 to 28 days. Abdominal wall contour and function were preserved.
      All dogs developed seromas, two of which became infected. One dog developed a
      hernia at the dorsal margin of the flap, which was repaired. At necropsy, there
      was no evidence of dehiscence in any of the dogs. Loose adhesions of omentum to
      the inner surface of the flap occurred in four dogs. Results of histologic
      examination confirmed the clinical impression of flap viability. The myofascial
      island flap has a wide range of mobility over the ventral and caudal areas of the
      abdomen and lateral thoracic wall. It has potential clinical use for
      reconstruction of defects within its arc of rotation.

PMID- 1369520
TI  - Open intestinal anastomosis with surgical stapling equipment in 24 dogs and cats.
AB  - Surgical stapling equipment was used to perform open antiperistaltic side-to-side
      ("functional end-to-end") entero-anastomoses in 20 dogs and 4 cats. Twenty-one
      anastomoses healed uneventfully. Seven animals with severe bacterial peritonitis
      required open peritoneal drainage and delayed abdominal closure. There was
      postoperative leakage at the anastomotic site in two dogs and a localized abscess
      at the staple line in one cat. No long-term complications occurred in follow-up
      periods of 3 to 29 months.

PMID- 1369521
TI  - Effect of tamoxifen citrate on canine immobilization (disuse) osteoporosis.
AB  - The effect of tamoxifen citrate on bone mass in immobilization osteoporosis was
      studied in 11 growing dogs. Immobilization osteoporosis was induced by fiberglass
      cast immobilization of the right hindlimb for 28 days, while the left hindlimb
      served as a nonimmobilized control. Six dogs received tamoxifen citrate (1.5
      mg/kg per os) once daily for 28 days; five dogs received no treatment. All dogs
      were euthanatized on day 28 and bone samples were collected. Bone mineral content
      of the distal tibial metaphysis of casted and uncasted limbs was measured by
      single photon absorptiometry. Immobilization resulted in a significant reduction
      in bone mass in the casted limb of untreated and tamoxifen-treated dogs. However,
      tamoxifen-treated dogs had less severe immobilization osteoporosis than untreated
      dogs. The calculated bone mass sparing effect of tamoxifen was 24.4%. Because of
      the complexity of pathologic bone remodeling, use of a single therapeutic agent
      may not be the optimal means of preventing bone loss associated with
      immobilization.

PMID- 1369522
TI  - Results of partial mandibulectomy for the treatment of oral tumors in 142 dogs.
AB  - Partial mandibulectomy was performed for the treatment of benign or malignant
      oral tumors in 142 dogs. Forty-two dogs with a benign tumor (ameloblastoma) had a
      22.5 month (range, 6 to 74 months) median disease-free interval, with a 97% 1
      year survival rate; there was local recurrence in one dog. Twenty-four dogs with
      squamous cell carcinoma had a disease-free interval of 26 months (range, 6 to 84
      months), with a 91% 1-year survival rate; recurrence and metastasis developed in
      two dogs and metastatic disease in one dog. Based on survival curves, 37 dogs
      with a melanoma had a median survival time of 9.9 months (range, 1 to 36 months),
      with a 21% 1-year survival rate; 20 dogs died or were euthanatized for recurrent
      or metastatic disease. Twenty dogs with osteosarcoma had a median survival time
      of 13.6 months (range, 3 to 28 months), with a 35% 1-year survival rate; nine
      dogs died or were euthanatized for recurrent or metastatic disease. Nineteen dogs
      with fibrosarcoma had median survival time of 10.6 months (range, 3 to 32
      months), with a 50% 1-year survival rate; 12 dogs died or were euthanatized for
      recurrent or metastatic disease. Results of this and previous studies
      demonstrated that partial mandibulectomy was effective in prolonging survival and
      decreasing recurrence for squamous cell carcinoma and ameloblastoma. Progressive
      disease and corresponding low survival times were common in dogs with melanoma,
      osteosarcoma, and fibrosarcoma. There were no differences in survival times or
      the progression of disease among five partial hemimandibulectomy procedures. The
      high rates of recurrence and metastasis in dogs with these tumors suggest a need
      for evaluation of ancillary chemotherapy and local radiation therapy to decrease
      the prevalence of progressive disease.

PMID- 1369524
TI  - Surgical management of atlantoaxial subluxation in 23 dogs.
AB  - Twenty-eight surgical procedures were performed in 23 dogs with atlantoaxial
      subluxation. Dorsal stabilization in seven dogs resulted in two recoveries and
      five failures of fixation. Ventral decompression and stabilization in 18 dogs
      resulted in eight recoveries and four failures of fixation. Six dogs died or were
      euthanatized within 7 days of ventral stabilization. Using either technique, four
      of seven nonambulatory dogs recovered.

PMID- 1369523
TI  - Treatment of forelimb growth plate deformity in 11 dogs by radial dome osteotomy
      and external coaptation.
AB  - Radial dome osteotomy and external coaptation were used to correct forelimb
      growth deformities with carpal valgus angles of 15 to 43 degrees in 11 dogs (12
      forelimbs). Osteotomy sites were clinically healed by week 4. Appearance and
      function in 10 limbs was good to excellent. The angular deformity recurred in one
      dog by week 4 due to partial closure of the distal radial growth plate. Carpal
      valgus recurred in one dog by week 2 because the ulnar osteotomy healed before
      radial growth ceased.

PMID- 1369525
TI  - Subdural hematoma in a dog.
AB  - A traumatic subacute subdural hematoma in a dog was diagnosed by computed
      tomography and treated successfully by craniectomy and surgical drainage.

PMID- 1369526
TI  - Endoscopic examination of normal paranasal sinuses in horses.
AB  - The frontal, caudal maxillary, and rostral maxillary sinuses of 10 equine
      cadavers were examined endoscopically, and the findings were confirmed by
      sinusotomy. Similar endoscopic examinations were performed in five conscious,
      adult horses by using sedation and local anesthesia. Useful portals of entry for
      the arthroscope in adult horses were: for the frontal sinus, 60% of the distance
      in a lateral direction from midline to the medial canthus and 0.5 cm caudal to
      the medial canthus; for the caudal maxillary sinus, 2 cm rostral and 2 cm ventral
      to the medial canthus; and for the rostral maxillary sinus, 50% of the distance
      from the rostral end of the facial crest to the level of the medial canthus and 1
      cm ventral to a line joining the infraorbital foramen and the medial canthus. The
      frontal sinus portal was most useful for examination of the frontal and caudal
      maxillary sinuses. The caudal maxillary sinus portal was most useful for
      examining the sphenopalatine sinus. Structures in the frontal and caudal
      maxillary sinuses could be approached surgically by viewing them through the
      frontal sinus portal and guiding an instrument to them through the caudal
      maxillary sinus portal. Tooth root identification was reliable for the second and
      third upper molars in animals older than 5 years, but was more difficult for the
      rostral teeth and in younger animals. Endoscopy was not difficult to perform and
      was well tolerated in standing, sedated horses. The only complication of this
      procedure was mild, local subcutaneous emphysema that resolved spontaneously
      within 14 days.

PMID- 1369527
TI  - The isolated perfused equine skin flap. Preparation and metabolic parameters.
AB  - A model for the study of equine cutaneous physiology, pharmacology, and
      toxicology was developed. Four 4 x 12 cm and twenty-one 6 x 12 cm single-pedicle
      axial pattern skin flaps based on the caudal superficial epigastric artery, and
      eight 6 x 12 cm flaps based on the saphenous artery and medial saphenous vein,
      were raised and sutured in a tubed configuration. On day 2, each flap was
      removed, the artery was cannulated, and the flap was perfused with a modified
      Krebs-Ringer's albumin-based medium for at least 6 hours. Flap viability was
      assessed by glucose use, lactate production, and histologic examination at the
      end of the perfusion period. The 4 x 12 cm flaps had evidence of skin necrosis,
      but the 6 x 12 cm flaps remained histologically viable. Results were compared to
      those previously reported from perfusion of porcine skin flaps based on the
      caudal superficial epigastric artery. While the ratios of glucose use to lactate
      production were similar, equine flaps used less glucose and produced less lactate
      per gram of tissue than similar pig flaps. Equine skin flaps perfused by
      saphenous vessels used more glucose and produced more lactate than flaps perfused
      by caudal superficial epigastric vessels. These results indicate that conclusions
      drawn from cutaneous physiology studies should not be extrapolated across species
      lines and that site-specific skin should be used for cutaneous physiology,
      pharmacology, and toxicology studies. The identified skin flaps may have
      applications in equine reconstructive surgery.

PMID- 1369528
TI  - Heterotopic transfer of fresh and cryopreserved autogenous articular cartilage in
      the horse.
AB  - Two 10 mm thick osteochondral grafts were harvested from the lateral aspect of
      the lateral trochlear ridge of the left talus in each of 10 anesthetized horses.
      The grafts were frozen in a 7.5% DMSO solution and stored in liquid nitrogen. The
      horses were anesthetized again on day 14 and the thawed grafts were press-fitted
      into drill holes in the trochlear ridges of the right stifle. A fresh graft was
      transferred from the right hock to the left stifle. To control for the effects of
      surgery, another fresh graft was transferred from the right stifle to the left
      stifle. The result was two grafts in each femoropatellar joint. Fresh and frozen
      osteoarticular autografts appeared to maintain a durable weight-bearing surface
      for 3 months; however, the fresh grafts were clearly superior. Frozen grafts had
      fewer living chondrocytes, decreased safranin-O staining, and decreased SO435
      uptake. Graft stability and articular surface congruency were determining factors
      in the outcome of all grafts. Since the availability of osteochondral autografts
      is limited, further work on the use of preserved allogeneic osteochondral tissue
      is warranted.

PMID- 1369529
TI  - Incorporation of fresh and cryopreserved bone in osteochondral autografts in the
      horse.
AB  - The structural integrity of subchondral bone in fresh and frozen osteochondral
      autografts was investigated at month 3 in 10 horses. Two osteochondral autografts
      were harvested from the lateral aspect of the lateral trochlear ridge of the left
      talus in each of 10 anesthetized horses. Grafts were frozen in 7.5% DMSO. After
      14 days, the thawed grafts were press-fitted into drill holes in the trochlear
      ridges of the right stifles. A fresh graft from the right hock was implanted in
      each left stifle. To control for the effects of surgery, a fresh graft was
      transferred from the right stifle to the left stifle. The end result was two
      grafts in each femoropatellar joint. Fresh and frozen bone grafts maintained a
      structurally intact support for the cartilage surface. Graft stability and
      surface congruency were determining factors in the outcome of the grafts.
      Incorporation of both types of graft was complete at month 3, but remodeling of
      the fresh grafts was more active.

PMID- 1369530
TI  - Femoral head ostectomy in horses and cattle.
AB  - Femoral head ostectomy was performed in six horses, three ponies, and four cattle
      for treatment of fractures of the femoral capital physis, coxofemoral luxation,
      fractured acetabulum, or severe degenerative joint disease. The procedures were
      performed via a cranial approach that did not involve osteotomy of the greater
      trochanter. A dorsal approach for femoral head ostectomy via osteotomy of the
      greater trochanter was evaluated in three healthy adult ponies. Three animals (2
      ponies, 1 calf) were euthanatized within a month and one horse was euthanatized
      at year 2 due to postoperative complications. Nine animals were discharged to
      owners and six of them fulfilled their intended functions of breeding, milking,
      and being kept as companions. One horse was lost to follow-up and two horses died
      of causes unrelated to the surgery. All surviving animals had a residual lameness
      that was described by owners as mild to moderate. None of the horses were used as
      riding animals. The mean age and weight of 10 animals that regained weight
      bearing locomotion was 3.1 months and 84 kg; for three unsuccessful cases it was
      34 months and 174 kg. We concluded that femoral head ostectomy was a viable
      salvage procedure for large animals with capital femoral physeal fracture,
      chronic coxofemoral luxation, or acetabular fracture. Surgical prognosis appeared
      to be favorable in young cattle and fair in young horses or ponies weighing less
      than 100 kg. Osteotomy of the greater trochanter resulted in superior exposure of
      the intact coxofemoral joint and allowed easier, less traumatic surgical luxation
      of the joint to facilitate femoral head ostectomy.

PMID- 1369531
TI  - Epidural vs. intramuscular oxymorphone analgesia after thoracotomy in dogs.
AB  - Oxymorphone was administered epidurally (0.1 mg/kg) or intramuscularly (IM) (0.2
      mg/kg) to 16 dogs undergoing thoracotomy, to compare the analgesic effectiveness.
      Heart rate, respiratory rate, systolic and diastolic blood pressure, and pain
      score were measured hourly. Arterial blood gases were measured at hour 1. A
      single dose of oxymorphone injected epidurally provided analgesia for up to 10
      hours, whereas the IM route provided a comparable effect for less than 2 hours.
      There were statistically significant increases in heart rate, and systolic and
      diastolic blood pressures at hour 2 in the dogs treated IM over the dogs treated
      epidurally. We conclude that epidurally administered oxymorphone is highly
      effective in alleviating pain after thoracotomy in dogs and provides longer
      lasting analgesia than the IM route.

PMID- 1369533
TI  - [Medical follow-up of drunken drivers reduces relapses dramatically].

PMID- 1369532
TI  - The influence of detomidine and epinephrine on heart rate, arterial blood
      pressure, and cardiac arrhythmia in horses.
AB  - Detomidine (10 micrograms/kg and 20 micrograms/kg) was administered to seven
      horses with and without epinephrine infusion (0.1 microgram/kg/min) from 5
      minutes before to 5 minutes after detomidine injection. One or more single
      supraventricular premature heartbeats were observed in three horses after
      detomidine administration. Epinephrine infusion did not modify the incidence of
      cardiac arrhythmias in detomidine-treated horses at the doses tested. Relatively
      high momentary peak systolic pressures were registered in some horses after
      detomidine administration during epinephrine infusion. The highest systolic
      arterial blood pressure was 290 mm Hg, but this value was not higher than that
      reported in horses during maximum physical exercise. Epinephrine infusion did not
      alter blood gases, arterial pH, or base excess.

PMID- 1369534
TI  - [The value of antibiotics in acute sore throat].

PMID- 1369535
TI  - On the teaching of operative surgery.

PMID- 1369536
TI  - Teaching and research of the art of medicine.

PMID- 1369537
TI  - Bayes theorem for the clinician.

PMID- 1369538
TI  - Fellowship of the Royal College of General Practitioners by assessment.

PMID- 1369539
TI  - Imaging of intracranial tumours--comparison of computed tomography and magnetic
      resonance imaging.

PMID- 1369541
TI  - An arts co-ordinator in a psychiatric hospital.

PMID- 1369540
TI  - Placental abruption following vaginal administration of prostaglandin E2 for
      induction of labour.

PMID- 1369543
TI  - Soap gets in your eyes.
AB  - We present a previously unreported series of five cases of acute angle closure
      glaucoma associated with watching the Australia soap opera "Neighbours". Two
      cases were bilateral and associated with watching two episodes of "Neighbours" on
      the same day. The pathogenesis, and possible role of watching soap operas in the
      causation of primary angle closure glaucoma is discussed.

PMID- 1369542
TI  - Mummification in ancient Egypt.

PMID- 1369544
TI  - To ski or not to ski--that is the question for skiers with replaced hips. A
      report on two friends.

PMID- 1369545
TI  - Prognosis by prophecy. A memoir of Carl Jung.

PMID- 1369546
TI  - [Possible role of sexual and gastrointestinal hormones on cancer of the digestive
      system].
AB  - This is a review of the most interesting studies on the possible role of sex and
      gut hormones in gastrointestinal (GI) carcinomas. Many experimental and some
      human studies suggest that sex and gut peptides may have a growth effect on
      normal or neoplastic gut cells. It may be possible in the future to develop
      strategies for patients with GI cancers that will be based upon hormonal
      manipulation in a manner similar to current strategies that are at present
      employed in the treatment of patients with breast cancer.

PMID- 1369547
TI  - [Comparative study of adriamycin, epirubicin and mitoxantrone in cancer of the
      breast. Review of the literature].
AB  - An overview of all published randomized trials which compared mitoxantrone or
      epirubicine to adriamycin was performed to analyse tolerance, toxicity and
      efficacy of these drugs, related to adriamycin. Mitoxantrone confirms its better
      tolerance: nausea and vomiting are less frequent (P < 10(-9)) and alopecia less
      intensive (P < 10(-9)). There is a significant decrease in cardiotoxicity
      occurrence with mitoxantrone (P < 0.01) but a significantly higher degree of
      leucopenia (P < 10(-4)). As far a response rate is concerned, mitoxantrone is
      somewhat less effective than adriamycin (P < 0.001). As compared to adriamycin,
      epirubicine does not reduce side effects incidence, nevertheless, their intensity
      is less important: nausea and vomiting (P < 0.04) and alopecia (P < 0.01).
      Leucopenia is less frequent following epirubicine administration as compared to
      adriamycin, documented course by course (P < 0.01) or on the overall treatment (P
      < 0.01). Epirubicine is noted to be less cardiotoxic than adriamycin (P = 0.001)
      with a decreased incidence of heart failures (P < 0.05). No difference can be
      observed in response rate between these two treatments, for objective as well as
      for complete responses.

PMID- 1369548
TI  - [Catheter rupture at the site of implantation: a rare accident? Apropos of 2
      observations].
AB  - Seventy three venous access ports of the same type have been implanted recently
      in our hospital. We have observed two cases of catheter's rupture. Both accidents
      show a lot of similarities: material of the same trade mark; same way of
      implantation: right subclavian vein; rupture before one year; rupture at the
      point of entry of the subclavian vein; migration of the distal part of catheter;
      withdrawal of this part by right femoral vein's catheterism. Both broken
      catheters and another not broken (implanted during more than one year) were
      tested. It appears that those catheters were weakened, especially around the
      rupture. The reason is the long-standing compression of the catheter at the
      narrow space between clavicle and first rib. Then, the rupture of this weakened
      catheter could have been produced by the high pressure due to injection with
      small syringes.

PMID- 1369549
TI  - [Angiosarcoma of the breast. Apropos of 4 cases with a review of the literature].
AB  - Four cases of angiosarcoma of the breast were treated at Centre Leon-Berard in
      Lyon. It is a rare malignant vascular tumor, constituting < 1% of all primary
      breast lesions. Radical local surgery is the treatment of choice; however, local
      recurrences and metastases are frequently observed. The 3-year disease-free
      survival rate is < 15%. The role of irradiation and adjuvant chemotherapy remains
      to be evaluated. Doxorubicin-ifosfamide-GM CSD gave a positive response in one
      case with metastases.

PMID- 1369550
TI  - [Measurement of the kinetics of cell proliferation of cancer of the oropharynx in
      vivo by the incorporation of bromodeoxyuridine and flow cytometry].
AB  - Forty-six tumors from patients with oropharyngeal carcinoma were analysed by flow
      cytometry after injection of bromodeoxyuridine (Budr) for the labelling index,
      the duration of S phase and the potential doubling time (Tpot). The results show
      large variations in Tpot (from 2.6 to 16.7 days) among these tumors from the same
      site and with the same histology. The variations in Tpot were not significantly
      related to TNM status and differentiation grade. However, aneuploid tumors had
      statistically significant shorter Tpot. The predictive value of Tpot regarding
      the response to radiotherapy is currently under investigation.

PMID- 1369551
TI  - [Characterization of a human cell line from an anaplastic carcinoma of the
      thyroid gland].
AB  - A new cell line derived from a thyroid anaplastic carcinoma, CAL 62, has been
      established in culture. This line is constituted by highly tumorigenic cells.
      Their epithelial phenotype is stable in culture. Immunochemical staining for
      human thyroglobulin is negative. Cytogenetic analysis showed a gain of chromosome
      20, the translocation i (14q), and breakpoints of centrometric chromatine. These
      results are similar to those previously reported by other investigators. CAL 62
      radiosensibility has been studied. The survival curve of the in vitro irradiated
      cells has been adjusted with a linear-quadratic model. This cell line is thus
      showed to be radioresistant. Cell line CAL 62 constitutes an appropriate model
      for in vitro studies of thyroid anaplastic carcinoma.

PMID- 1369552
TI  - [Plasma pharmacokinetics of morphine and morphine-6-glucuronide using high
      performance liquid chromatography and colorimetric detection].
AB  - This pilot study was undertaken in a group of 7 patients receiving morphine
      either by oral route under a controlled release form (Moscontin tablets), or by
      subcutaneous route with continuous infusion. Complete pharmacokinetics over 24 h
      were carried out with blood samples taken every hour. The measurements of
      morphine and of its metabolite, morphine-6-glucuronide (M6G) were performed by
      high-performance liquid chromatography (HPLC) with coulometric detection, using
      nalorphine (NAL) as an internal standard. The morphinics were extracted on a Bond
      Elut C18 column according to a double liquid-solid extraction. The extract was
      chromatographed by ion-pairing on a mu Bondapak C18 column, 10 microns (300 x 3.9
      mm). The minimal detectable concentrations were respectively 1 and 5 ng/ml for M
      and M6G. When Moscontin was given at dosages < 1 mg/kg/d, the areas under the
      curve over 24 h (AUC 24 h) of M were rather close to those of M6G (ratio 1.1 +/-
      0.1). However, with dosages > 1 mg/kg/d, a difference appeared and gradually rose
      to a M/M6G ratio of 1.3 +/- 0.04. With subcutaneous infusion, the plasma levels
      of M6G were from 2 to 17-fold lower than those of M.

PMID- 1369553
TI  - [Hypothalamo-hypophyseal and gastric metastasis of a breast neoplasm. Clinical
      case and a review of the literature].
AB  - The authors report the case of a young woman with advanced breast cancer who
      developed diabetes insipidus due to pituitary involvement and also gastric
      metastases. This patient had a normal brain CT scan. Gastric metastases were
      diagnosed when she was operated for a perforated gastric ulcer. Although very
      rare, and even if the brain CT scan is normal, pituitary metastases should be
      diagnosed in the presence of suggestive clinical symptoms. Abdominal pain also
      warrants investigation in these patients in an early attempt to document any
      possible gastric metastases.

PMID- 1369554
TI  - [Pilot study of chemotherapy with mitoxantrone, ifosfamide, 5-fluorouracil in
      metastatic cancers of the breast. Preliminary study].

PMID- 1369555
TI  - [Adverse effects of interleukin 2].
AB  - Interleukin 2, has frequent and important side effects. Toxic effects observed
      are systemic (fever, chills, malaise), hemodynamic (capillary leak syndrome,
      hypotension), cardiac (arrhythmia, infarction), renal (renal dysfunction),
      infectious (septicemia), cutaneous, hematologic, gastrointestinal, endocrinologic
      and metabolic. Side effects are dose-dependent, generally reversible, with a
      mortality from 1 to 3%. Regimens of administration and other cytokine
      combinations affect interleukin 2 toxicity. If the treatment of these side
      effects is well known, selection of patients and specialized care unit remain
      always necessary.

PMID- 1369556
TI  - [The Pavlov Physiology Department (on the centenary of its founding)].

PMID- 1369558
TI  - [The participation of cortical brain areas in the processes of perceiving and
      reproducing human emotional states].
AB  - New method of mapping intracortical interactions was used to study the
      participation of cortical brain areas in the processes of perception and of
      mental reproduction of emotional states in humans. When an emotion was
      identified, the activity focus was observed in the left temporal cortex. If
      emotion was not identified, the temporal focus did not appear, but activity foci
      were seen in frontal regions of both hemispheres. When emotional states were
      mentally reproduced, activity foci were encountered mostly in the frontal
      cortical areas.

PMID- 1369557
TI  - [The hypothesis of the cortical mechanisms of operative memory].
AB  - The investigation of neuronal activity of monkey cerebral cortex during delayed
      spatial choice performance allows to develop a hypothesis about the neuronal
      networks securing the operative memory. The work of one of them is based on the
      relay-race and reverberation principles of information transfer. Another neuronal
      network secures the reliability of the transfer phases of behavioural program.
      Both of these neuronal networks are represented differently in the prefrontal and
      parietal associative cortical areas.

PMID- 1369559
TI  - [The characteristics of probabilistic prognosis and of the orienting reaction in
      children with learning difficulties].
AB  - Middle-aged school-children were examined with learning disabilities,
      differentiated by the parameters of probabilistic prognosis in two subgroups:
      with disturbances of attention (1) and memory (2). The first subgroup differed
      from the norm by intensified reaction of desynchronization of the projection
      areas of the cortex to irrelevant stimuli. Relevant information evoked an
      increase of activation of the associative zones, less expressed than in the norm.
      In the second subgroup a weak involvement of associative cortical areas in the
      reaction of desynchronization to relevant stimuli correlated with insufficient
      formation of alpha 2-rhythm and high frequency of meeting the signs of
      dysfunction of mesodiencephalic brain structure. The results are discussed in the
      aspect of the role of neurophysiological mechanisms of regulation and trace
      fixation for the formation of the integrative brain activity in the ontogenesis.

PMID- 1369560
TI  - [The characteristics of motor asymmetry in the ontogeny of calves].
AB  - The side of preference (first turn of head) was recorded in calves in situation
      of free equal probability two-sides choice, and rate of reconstruction of
      conditioned reflex to food presented from the left or from the right was
      determined. Initially the calves preferred the left turn, i.e. manifested motor
      asymmetry. Preference to the left turn changed depending on the calves age with
      the period of 22-23 days. The rate of conditioned reflexes reconstruction was
      higher in calves with the left-side preference. Correlation of the motor
      asymmetry and rate of conditioned reflex reconstruction in calves of different
      age changed in analogy with age changes of asymmetry. Probably the observed
      periodical changes of asymmetry and its correlation with the rate of
      reconstruction reflect formation of interhemispheric interactions in regulation
      of the organism functions in animals ontogenesis.

PMID- 1369561
TI  - [A computer analysis of EEG intersignal reactions during the the acquisition of
      conditioned motor-food reflexes in dogs].
AB  - Background electric activity was studied of different neocortex areas in
      interstimulus intervals at the stage of generalization during elaboration of
      motor alimentary conditioned reflexes in dogs. For this stage the appearance is
      typical of short-term (0.1-0.3 s) packs of high frequencies (above 40 osc./s)
      significantly exceeding the adjacent initial background by frequency and
      amplitude (along side with motor interstimulus reactions). The index of specific
      variation, elaborated by us, allowed to single out this EEG pattern in the
      initial realizations of the background activity during their input in the
      computer. With the purpose of further evaluation of the above phenomenon
      parameters non-standard approaches of computer analyses were used, directed to
      decomposition of the EEG curve into the system of oscillations and receipt of
      corresponding amplitudes frequencies distributions (maps). It was shown, the
      described high frequencies packs were localized on these maps in definite
      sufficiently compact places.

PMID- 1369562
TI  - [The effects of intracerebral injections of kynurenine on conditioned reflex
      activity and on the serotonin level of the blood in dogs].
AB  - Higher nervous activity of dogs was studied by classical Pavlovian method of
      alimentary salivary conditioned reflexes and serotonin content in blood was
      measured. Kynurenine sulfate in a dose of 300 + 300 mkg (bilaterally) was
      injected in the dorsal hippocampus region through chemiotrodes. In most cases the
      injection of the substance led to changes towards excitation (increase of
      conditioned and unconditioned alimentary salivation in the day of injection and
      the next day) and also to a rise of serotonin content in animals blood.

PMID- 1369563
TI  - [The regulatory effect of the functional status of the cat on the perception of
      an external afferent stimulus].
AB  - Experiments were conducted on cats by conditioned food-procuring method.
      Behavioural, vegetative reactions and a set of electrophysiological
      characteristics were recorded. It was found that regulatory influence of an
      extraneous stimulus and of artificial excitation of the brain was expressed in an
      increase of reactivity to conditioned and unconditioned sensory stimuli and in
      disinhibition of effector responses. This influence was realized not only during
      the development of EEG activation reaction but could be preserved over a long
      period in conditions of the deactivated brain state. Regulatory influence of
      interceptive factors is characterized by a decrease of reactivity and by
      inhibition of effector responses. As in the case of external effects, the
      realization of this influence begins with a period of brain activation and is
      preserved for a long time in conditions of deactivated state.

PMID- 1369564
TI  - [The effect of the S1A-receptor agonist ipsapirone on behavior types in wild and
      domesticated rats].
AB  - Selective agonist of 1A subtype of serotonine receptors ipsapirone inhibited
      manifestation of affective kinds of aggression in wild and domesticated rats.
      Administration of ipsapirone (10 mg/kg) decreased the number of aggressive
      attacks of wild and domesticated rats in the test of shock-induced aggression and
      blocked manifestation of defensive reaction to the experimenter in wild rats.
      Neophobia in wild rats decreased under the influence of ipsapirone. At the same
      time ipsapirone did not change mouse-killing behaviour either in wild or in
      domesticated rats. Probably, 5-HT1A receptors the aggressive regulate reaction,
      which are parts of the complex of defensive behaviour of the wild animals.

PMID- 1369565
TI  - [The capacity of ants for multiple alterations in the maze habit].
AB  - Ability was shown of ants Myrmica rubra to multiple reconstructions of the habit
      elaborated in symmetrical multialternative maze under motivation of care for the
      progeny (transportation of breed of the own species). Reconstruction consisted in
      the change of reinforcement location on the left or right aim spot. The ants
      showed the ability to carry out the series of eight reconstructions during one
      two days. An improvement took place of the fulfillment of the last
      reconstructions in comparison with the first ones. Peculiarities of learning and
      reconstructions were found in two groups of animals differing by conditions of
      learning: at reinforcement on both ain spors or on one of them. The results
      obtained are considered as indices of high plasticity of the behaviour of ants of
      the studied species.

PMID- 1369566
TI  - [The participation of the neostriatal cholinergic system in the differentiation
      of acoustic signals in dogs].
AB  - In chronic experiments on six dogs the influence was studied of micro-injections
      of choline agonist carbocholine (0.05-0.2 mkg) and of blocker of choline
      receptors atropine (40 mkg) in the caudate nucleus head of the left and right
      hemispheres on realization of instrumental defensive reflexes, connected with the
      maintenance of definite posture and on differentiation of signals in defensive
      situation. It has been shown that the cholinergic system of the neostriatum
      participated in realization of both the motor and sensory mechanisms in
      connection with the realization of motor responses to defensive and
      differentiation signals. Analysis of the obtained results also allowed to make a
      conclusion that the influence of carbocholine micro-injections into the
      neostriatum on differentiation depended on a number of factors: it did not take
      place when the signal was poorly distinguished (judging by the values of motor
      components to defensive and differentiation signals) or, on the other hand,
      against the background of stable differentiation reaction in other animals, i.e.
      in case of complete learning.

PMID- 1369567
TI  - [The effect of high-frequency stimulation of the midbrain reticular formation on
      the interaction of neocortical neurons].
AB  - The influence was studied of midbrain reticular formation (NRT) stimulation at
      the rate of 75-100 Hz by the current of 33-400 mkA upon the neuronal interaction
      in the visual and somatosensory regions of rabbits neocortex. Histograms of cross
      and autocorrelation of impulse trains were plotted. NRT stimulation resulted (as
      compared with calm wakefulness) in an increase of the number of pairs of neurons
      with correlated activity and in an increase of the probability of neurons
      discharges 100-400 ms one after another. Mechanisms of cellular interaction did
      not change. Comparison with the previously obtained data allowed to conclude that
      NRT activation can induce certain changes in neuronal interaction observed during
      pseudoconditioning and early phases of conditioning.

PMID- 1369568
TI  - [The intercentral relations of the biopotentials in the rabbit brain during the
      creation of a blinking dominant].
AB  - On rabbits in chronic experiment intercentral relations were studied of
      biopotentials of the sensorimotor cortical zone (blinking presentation in the
      cortex), VPM of the thalamus and motor nucleus of the oculomotor nerve at
      formation of blinking dominant created by serial stimulation of one eye by air
      jet. By the method of spectral-correlation analysis an increase was revealed of
      spectrum power and increase of COG of the potentials in delta-range in the
      structures connected with blinking function of the stimulated eye. At transition
      of the dominant focus to the inhibitory state and activation of the symmetrical
      centre of the other eye, in centers constellation of this induced focus a
      reconstruction of the electrical processes took place typical for the dominant.

PMID- 1369569
TI  - [The effect of acetylcholine and atropine on the temporal connection in the
      neuronal populations of the motor cortex].
AB  - On alert non-immobilized rabbits the activity of neurones in the sensorimotor
      cortex was studied at pair combination of brain structures stimulations. During
      omission of the reinforcing stimulus at the place of its expected presentation a
      complicated complex develops of neurones impulses reconstructions, consisting in
      reproduction of responses and activity changes which by their configuration
      differ from them and usually appear in later terms. Direct acetylcholine
      application on the cortex promotes manifestation of both types of neurones
      activity reconstructions. But atropine application depresses mainly the second
      type of reconstructions. Besides, acetylcholine increases the general duration of
      the given conditioned effects, but atropine decreases it.

PMID- 1369570
TI  - [The functional testing of the interhemispheric asymmetry in the spatial
      organization of rabbit cortical potentials].
AB  - Interhemispheric asymmetry was studied of spatial-temporal potentials
      organization (STPO) of the cortex in non-fixated animals in the states of deep
      rest, behavioural activity and in the transition period between them. Despite the
      intrahemispheric differences of the STPO in each of these states,
      interhemispheric divergences in the character of reconstructions of momentary
      topograms of the cortical potentials, recorded at 24-channels leading, are
      limited by 35% of the epoch analysis time. Comparison of the dynamics of
      intrahemispheric changes of topograms of cortical potentials in the left and
      right hemispheres in the states of rest and activity revealed a narrowing of
      temporal period of the absence of resemblance in reconstructions of successive
      topograms of the left and right hemispheres in comparison with transition
      processes. In the phase of rest the interhemispheric conjugation of spatial
      reconstructions in topograms became lowered mainly because of the disturbances of
      monotony of changes of their reliefs in one of the hemispheres in turn. In the
      active phase, deviations from STPO of the cortex, characteristic of the state of
      rest, were met more frequently in the right hemisphere; in that case oscillations
      of the topograms general mean level connected with the activity of non-specific
      activating subcortical brain system acquired a significant role in regulation of
      interhemispheric relations. Presence of interhemispheric resemblance of
      reconstructions of topograms reliefs in the active phase, despite the tendency to
      its lowering in comparison with the rest, testifies to the contribution also of
      the intracortical processes to the interhemispheric spatial synchronization of
      the cortical potentials in this state.

PMID- 1369571
TI  - [Lipoxygenase inhibitors, eicosapolynoic acids, attenuate the short-term
      plasticity of the cholinoreceptors of snail neurons].
AB  - On identified Helix neurones RPa3 and LPa3 with the use of the double-electrode
      voltage clamp technique on the membrane the influence was studied of three
      polyacetilenic analogues of natural polyenoic acids which were the inhibitors of
      their lipoxygenase oxidation on the dynamics of inward current extinction, caused
      by the repeated iontophoretic applications of acetylcholine to soma. It was found
      that 5, 8, 11, 14-eicosatetraynoic acid (30-60 microM) and 5, 8, 11, 14, 17
      eicosapentaynoic acid (4-5 microM) decreased the amplitude of inward current
      caused by acetylcholine leading and weakened its extinction at the repeated
      applications. The third analogue -8, 11, 14-eicosatrynoic acid had no modulating
      influence on the value of current and on its extinction. The supposition was made
      that lipoxygenase metabolites of polyenoic acids regulated plasticity of Helix
      neurones cholinoreceptors. Considering different inhibiting by the used compounds
      of various lipoxygenases the most probable was participation in regulation of
      cholinoreceptors plasticity of those eicosanoids which were formed from
      arachidonic acid under the influence of 5-lipoxygenase. Regulating role of
      eicosanoids formed at the action of other lipoxygenases was not excluded.

PMID- 1369572
TI  - [Cholinergic sensitivity as an index of the functional differences in cortical
      neurons in young and old rabbits].
AB  - Acetylcholine-sensitivity of motor cortex neurons was studied in the young and
      old rabbits. Muscarinic-type excitation in the neurons of old animals was
      revealed twice less frequently compared to the young ones. The age-related fall
      in the number of cholinoceptive neurons may be due to general decrease of
      neuronal activation in the motor cortex during aging. Changes in functional
      properties of motor cortex neurons with age may have a result that firing rate of
      movement related neurons becomes insufficient for the effective control of motor
      function.

PMID- 1369573
TI  - [The capacity for competition in rats raised in isolation].
AB  - It is shown, that rats, bred in conditions of intraspecies isolation are able to
      competition for water in the kin group, having usual experience of intraspecies
      intercourse. At the same level of drinking motivation in conditions of
      competition for water the intraspecies activity is significantly higher in rats,
      bred in isolation in comparison with grouped animals. Rats-isolants significantly
      more often than the grouped animals use extraordinary tactics of intraspecies
      behaviour, which increase their competitive ability in conditions of limited
      access to water.

PMID- 1369574
TI  - [The predisposition to catatonic reactions, monoamine oxidase and the delta-sleep
      peptide in rats].
AB  - MAO B/MAO A rations and the influence of delta-sleep inducing peptide (DSIP) on
      the two forms of MAO and on the predisposition to different types of catatonic
      reactions were compared in rats of GC strain selected from Wistar for
      predisposition to catalepsy, and in wild rats. In GC rats, the MAO B/MAO A ratio
      was increased, as compared to Wistar, in the brain stem and hemispheres, whereas
      in wild rats predisposed to catatonia it was increased, as compared to normal
      wild rats, only in the hemispheres. In GC rats, this increase of the MAO B/MAO A
      ratio was due to a decrease of MAO A and increase of MAO B activity, while in
      wild catatonic rats only due to heightened MAO B activity. Administration of DSIP
      abolished the susceptibility to catatonic reactions and normalized the MAO B/MAO
      A ratio both in GC and in wild catatonic rats. There seems to be a partial
      similarity of physiological mechanisms of catatonic reactions in laboratory
      albino and in wild rats.

PMID- 1369575
TI  - [The characteristics of the change in the catecholamine content of the brain in
      inbred mouse strains under zoosocial stress].
AB  - Noradrenaline (NA) and dopamine (DA) contents in various brain regions and their
      dependence on genotype, determining predisposition to domination, were studied
      during 7 days after the formation of artificial micropopulations consisting of 6
      male mice of different genotypes. Significant changes of NA level were found in
      the olfactory bulbs and in the medulla oblongata and of DA in the hypothalamus
      and the hippocampus. Genotypic differences in NA levels were found in the
      hypothalamus and in DA levels--in the hippocampus. Reactions of RT males
      predisposed to domination differed both in noradrenaline and DA systems of the
      brain from the reactions of the males genetically predisposed to subordinate type
      of behaviour. Interconnection between the amines content both inside and between
      catecholamine systems was revealed.

PMID- 1369576
TI  - [The intravenous self-administration of narcotics in mice].
AB  - Four commonly and largely abused drugs morphine, cocaine, amphetamine, cathinone
      and sympathomimetic ephedrine were investigated, using intravenous self
      administration by naive mice, with special regard to methodological aspects of
      these techniques. All drugs showed a similar bell-shaped concentration response
      curves, which are typical of compounds with high addictive potential. A new
      method of analysis of the reinforcing properties allowing to disregard motor side
      effects of drugs nas been proposed. Procedure and analysis aspects of described
      techniques as well as the possibilities of its application for screening of
      addictive substances are discussed.

PMID- 1369577
TI  - [The effect of the fixation time on the performance of a motor task by a monkey].

PMID- 1369578
TI  - [The neuronal reactions of the rabbit sensorimotor cortex to stimuli of different
      sensory modalities against a background of the action of the protein-synthesis
      blocker actinomycin D].

PMID- 1369579
TI  - [The effect of antibodies to brain-specific non-histone chromatin proteins on the
      acquisition and reproduction in rats of a passive-avoidance conditioned
      reaction].

PMID- 1369580
TI  - [A method for the acquisition of the conditioned-reflex switching of motor-food
      and escape reflexes in rabbits].

PMID- 1369581
TI  - [Unknown pages of the history of science from the archives of L. A. Orbeli (1882
      1958)].

PMID- 1369582
TI  - [Use of an endoprosthesis in the treatment of bile leakage from the cystic duct
      following laparoscopic cholecystectomy].
AB  - The case is reported of a female aged 32 years in whom, after laparoscopic
      cholecystectomy performed because of symptomatic gallbladder calculi, leakage
      from the cystic duct occurred. After percutaneous drainage of the perihepatic
      bile collection, endoscopic retrograde cholangiopancreatography (ERCP) with
      papillotomy was performed; since this proved insufficient, an endoprosthesis was
      inserted into the common bile duct by ERCP, following which the bile leakage
      ceased.

PMID- 1369583
TI  - Differential tissue regulation of the insulin-like growth factors in rats bearing
      the MStT/W15 pituitary tumor.
AB  - The content of insulin-like growth factors, IGF-I and IGF-II, was measured in
      tissues of rats bearing a transplantable mammosomatotrophic tumor, MStT/W15.
      Serum IGF-I was elevated in tumor-implanted rats [2,557 +/- (SE) 419 vs. 891 +/-
      100 ng/ml], and tumor tissue concentrations of IGF-I were increased (321 +/- 16
      ng/g) in comparison to control liver tissue (160 +/- 5 ng/g) or control pituitary
      (80 +/- 3 ng/g). The IGF-I levels were significantly increased in most peripheral
      tissues in the tumor-bearing rats with the exception of the liver. In support of
      this finding, messenger RNA for prepro IGF-I was likewise not increased in the
      livers of tumor-bearing rats, nor was there an increase in the growth hormone
      dependent IGF-binding protein, BP-3, in the liver or serum of these animals. All
      tumors had detectable levels of prepro IGF-I mRNA which was, however, less than
      50% of that noted in normal control liver. The tumors also expressed an IGF-BP
      which was identified as IGF-BP-2 by immunoblotting. Serum concentrations of IGF
      II were similar in control and tumor-bearing animals (approximately 70 ng/ml).
      IGF-II levels in the tumor (90 +/- 5 ng/g) were significantly higher than levels
      in control liver (34 +/- 2 ng/g), but similar to those found in normal pituitary
      (165 +/- 24 ng/g). In peripheral tissues, IGF-II concentrations were selectively
      increased in skeletal muscle and heart of tumor-bearing rats. These data
      demonstrate tissue-specific regulation of IGF-I and IGF-II. Paradoxically, the
      liver does not appear to be stimulated over control levels by high serum growth
      hormone levels, since neither IGF-I peptide, IGF-I mRNA, nor IGF-BP-3 levels are
      increased in livers of tumor-bearing rats. This suggests that the increase in
      serum IGF-I in these animals is due to increased production of IGF-I by the
      tumors themselves and by nonhepatic peripheral tissues and further that hepatic
      responsiveness to growth hormone is diminished in these tumor-bearing animals.

PMID- 1369584
TI  - Effect of elevated serum prolactin concentrations on cytokine production and
      natural killer cell activity.
AB  - In vitro and in vivo studies in rodents and human suggested an immunostimulatory
      effect of prolactin. The aim of the present study was to determine the impact of
      chronically elevated serum prolactin concentrations on the immune system in
      patients with prolactinomas. For this purpose parameters of the humoral and
      cellular immune system were studied in seven patients with prolactinomas on two
      occasions (1) when their serum prolactin concentration had been normalized
      through treatment with dopamine agonists and (2) when their serum prolactin
      concentration was high. Serum concentrations of immunoglobulines, interleukin 1,
      3 and 6, TNF-alpha, interferon-gamma and the soluble interleukin 2 receptor,
      leukocyte subsets and the natural killer cell activity were found to be within
      the normal range on both occasions, i.e. at normal and at high serum prolactin
      concentrations. The assumption could be made that long-lasting elevation of serum
      prolactin concentration induces adaptive changes when the acute stimulatory
      effects of prolactin on several parameters of the immune system have subsided.

PMID- 1369585
TI  - Alterations in gonadotropin secretion in middle-aged persistent-estrous rats
      following LHRH agonist treatment.
AB  - During aging female rats enter an anovulatory condition with chronically elevated
      circulating levels of estrogen described as persistent estrus (PE). Since this
      endocrine state is dramatically different from the fluctuating steroid milieu of
      young regularly cycling females, interpretations of altered neuroendocrine
      responses in aged rats have been difficult to attribute to aging per se. In the
      present study, young cyclic and middle-aged PE rats were treated with an LHRH
      agonist, [DTrp6,Pro9-NHEt]-LHRH, continuously (2.5 micrograms/h) for 12 days to
      suppress gonadotropin and ovarian steroid secretion. On the evening of the first
      day of LHRH agonist (LHRH-AG) treatment both young cyclic and middle-aged PE rats
      showed marked (p < 0.01) increases in plasma LH and FSH followed by progressive
      decreases in gonadotropin secretion which reached significantly (p < 0.05) lower
      levels than pretreatment values by day 7. LHRH-AG treatment significantly (p <
      0.01) reduced circulating 17 beta-estradiol (E2) levels in both young and PE rats
      while progesterone concentrations did not change. Following LHRH-AG treatment,
      ovariectomy (OVX) resulted in increases of plasma LH and FSH that were delayed
      and attenuated in PE rats as compared to those of young females. When compared to
      nontreated rats, 12 days of LHRH-AG treatment in both young and PE females had a
      minimal and transient effect on the post-OVX gonadotropin responses, suggesting
      that the endocrine status immediately prior to OVX does not profoundly influence
      the post-OVX responses in young cyclic and middle-aged PE rats. Furthermore, LHRH
      AG treatment does not appear to have permanent inhibitory effects on the
      hypothalamic-pituitary axis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369586
TI  - Early complete maturation of proenkephalin processing induced by dexamethasone in
      the adrenal gland of neonatal rats.
AB  - We have previously found that proenkephalin processing is incomplete in the
      neonatal rat adrenal medulla and have postulated that immaturity of either the
      nervous input to the gland or the endocrine hypothalamus-pituitary-adrenal axis
      might be involved in the failure of the gland to yield free met-enkephalin.
      Therefore, we investigated whether cholinergic and glucocorticoid agonists may
      act in vivo on neonatal proenkephalin processing; reserpine, a strong activator
      of precursor cleavage, was also tested. Acute administration of nicotine,
      pilocarpine and reserpine to 24-hour-old rats increased the content of enkephalin
      containing peptides (ECP) after 72 h (4-day-old rats) and activated the
      posttranslational processing of proenkephalin to high, intermediate and low
      molecular weight peptides respectively, although free met-enkephalin was not
      produced. Chronic treatment with nicotine and pilocarpine neither modified the
      concentration of ECP nor were able to induce free metenkephalin production.
      Chronic administration of dexamethasone increased ECP levels in the adrenal of 4
      day-old rats and caused proenkephalin processing to intermediate- and low
      molecular-weight products including the production of free met-enkephalin. These
      results indicate that only dexamethasone was able to induce the production of met
      enkephalin in the adrenal of neonatal rats, suggesting an involvement of the
      hypothalamus-pituitary-adrenal axis in the proteolytic maturation of
      proenkephalin during the ontogeny of rat adrenal medulla.

PMID- 1369587
TI  - Activation of 5-HT1A receptor subtype in the paraventricular nuclei of the
      hypothalamus induces CRH and ACTH release in the rat.
AB  - Previous studies have shown that activation of the 5-HT1A receptor subtype
      enhances rat plasma ACTH concentration. Such receptors have been suggested to be
      located on CRH neuronal cell bodies in the paraventricular nuclei of the
      hypothalamus (PVN). In this report, microinjection of 8-hydroxy-2-(di-n
      propylamino) tetralin (8-OH-DPAT), a selective 5-HT1A agonist, into the PVN
      increased rat plasma ACTH concentration in a dose-related manner. Similar
      responses were observed when two other 5-HT1A agonists, busipirone and gepirone,
      were used. (+/-)-Pindolol, known to have 5-HT1A antagonist properties, blocked
      the effect induced by an optimal dose of 8-OH-DPAT after injection into the PVN.
      This same dose of 8-OH-DPAT also induced a decrease of hypothalamic CRH
      concentration, which was completely antagonized as well by pretreatment injection
      of (+/-)-pindolol into the PVN. A significant inverse correlation was found
      between hypothalamic CRH and plasma ACTH levels. These results confirm that
      elevation of the plasma ACTH concentration induced by 5-HT1A receptor subtype
      activation is mediated by the release of CRH from the paraventricular nuclei of
      the hypothalamus in rats, but do not exclude other mechanisms.

PMID- 1369588
TI  - Transient hyponatremia after damage to the neurohypophyseal tracts.
AB  - Section of the neurohypophyseal stalk classically produces a triphasic response:
      diabetes insipidus (1st phase), hyponatremia or normonatremia (2nd phase), and
      diabetes insipidus (3rd phase). Transient hyponatremia without diabetes insipidus
      has been reported after transsphenoidal pituitary surgery. We report two
      additional cases of transient hyponatremia which occurred 6-8 days after
      pituitary surgery. We hypothesize that this outcome may be due to partial section
      or damage of the hypothalamiconeurohypophyseal tracts. The remaining intact
      vasopressin neurons function normally to protect against the diabetes insipidus
      of the first and third phase, but leak of vasopressin from the damaged tracts and
      posterior pituitary is sufficient to cause what can be described as an isolated
      second phase. To study this hypothesis in rats, partial damage to the
      hypothalamicneurohypophyseal tracts was produced by radiofrequency lesions. The
      lesions did not affect anterior pituitary function. A variety of responses in
      posterior pituitary function occurred, including classic triphasic response in 2
      rats and transient hyponatremia in 20 of 35 lesioned animals. The mean sodium
      nadir was 128.7 +/- 1.5 mEq/l in comparison to the sham-operated value of 140.0
      +/- 0.4 mEq/l. Of the 20 rats exhibiting transient hyponatremia, 12 went on to
      develop diabetes insipidus, and 8 recovered. In the recovered group, the
      transient hyponatremia occurred 1-3 days after lesioning and returned to normal
      by day 7 which corresponds to the timing of the second phase of the triphasic
      response in rats. Hyponatremia was accompanied by vasopressin levels
      inappropriate for the plasma sodium level, inappropriately concentrated urine,
      water retention, and natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369590
TI  - Opioid inhibition of luteinizing hormone secretion compared in developing male
      and female sheep.
AB  - The sheep exhibits a marked sex difference in the timing of the pubertal increase
      in luteinizing hormone (LH). Male lambs undergo a reduction in sensitivity to
      inhibitory steroid feedback, leading to an increase in LH by 10 weeks of age, but
      females remain hypersensitive until 30 weeks of age. Endogenous opioids suppress
      LH secretion in the female lamb prepubertally and in adult male and female sheep.
      It has been suggested that a reduction in opioid inhibition of LH secretion is
      the signal to time puberty. Therefore, if a decrease in opioid tone occurs during
      sexual maturation, it should begin earlier in the male lamb than in the female.
      The objective of this study was to compare opioid inhibition of LH secretion in
      male and female lambs in relation to the timing of puberty. Our approach was to
      examine the response to the opioid antagonist naloxone at various ages in both
      sexes. To determine the timing of the pubertal LH rise in the presence of
      constant inhibitory steroid feedback, male and female lambs (n = 5 each) were
      gonadectomized at 3 weeks of age and implanted with a Silastic capsule of
      estradiol. They were then challenged with naloxone at 5, 11, and 23 weeks of age;
      blood samples were collected every 12 min for 8 hours, and lambs received
      naloxone (1 mg/kg i.v.) at hours 4, 5, 6, and 7. Mean LH before and during
      naloxone treatment was compared at each age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369589
TI  - Immunocytochemical localization of beta endorphin and gonadal steroid regulation
      of proopiomelanocortin messenger ribonucleic acid in the ewe.
AB  - In the ewe, estradiol and progesterone inhibit luteinizing hormone (LH) secretion
      during the breeding season. Endogenous opioid peptides (EOP) are also inhibitory
      to LH secretion, and both estrogen and progesterone have been reported to enhance
      EOP inhibition of LH release. Which EOP are involved in this inhibition is
      unclear. In this study, we concentrated on beta-endorphin because evidence for
      its ability to inhibit LH secretion exists in ewes. We first studied the
      distribution of beta-endorphin-immunoreactive neurons in 4 cycling ewes using
      immunocytochemistry. Cell bodies were found only within the medial basal
      hypothalamus (MBH) and were concentrated in arcuate nucleus and mammillary recess
      of the third ventricle, with a few in the median eminence. Extensive fiber tracts
      were seen in preoptic area (POA) and median eminence. We next tested the
      hypothesis that gonadal steroids increase the synthesis of EOP by measuring
      levels of mRNA for proopiomelanocortin (POMC), the precursor to beta-endorphin.
      Ovariectomized ewes were treated with no steroids (n = 7) or given subcutaneous
      Silastic implants containing either estradiol (n = 6) or progesterone (n = 6).
      After 4 days of treatment, EOP inhibition of LH secretion was measured by
      determining the LH response to WIN 44,441-3 (WIN), an EOP antagonist. LH pulse
      frequency and pulse amplitude were determined in blood samples collected at 12
      min intervals for 3 h before and after intravenous administration of 12.5 mg WIN.
      WIN injection increased (p < 0.01) the LH pulse-frequency only in progesterone
      treated and pulse amplitude only in estradiol-treated ewes. After blood sampling,
      the ewes were killed, and POA, MBH, and pituitary gland were removed. Total RNA
      was extracted from these tissues and dot blotted onto nitrocellulose membranes
      for hybridization with a DNA probe complementary to the POMC mRNA. The resulting
      autoradiographs were quantified densitometrically. Levels of POMC mRNA in the MBH
      were increased (p < 0.01) by both estradiol and progesterone as compared with the
      no steroid group. There was no detectable POMC mRNA in the POA. These results
      suggest that estrogen and progesterone enhance EOP inhibition of LH secretion by
      increasing POMC mRNA levels and thus synthesis of beta-endorphin.

PMID- 1369591
TI  - Inhibitory effects of the new bombesin receptor antagonist RC-3095 on the
      luteinizing hormone release in rats.
AB  - The effects of bombesin receptor antagonist RC-3095 and gastrin-releasing peptide
      [GRP (14-27)] on basal luteinizing hormone (LH), follicle-stimulating hormone
      (FSH), and testosterone levels, as well as on the release of LH and FSH in
      response to LH-releasing hormone, were studied in normal and castrated male rats.
      We also examined the release of LH and FSH after intracerebroventricular
      injection of RC-3095 under different types of anesthesia (urethane, sodium
      pentobarbital, Metofane). Following injection of 10 micrograms RC-3095 into the
      lateral brain ventricle, serum LH levels were rapidly and significantly (p <
      0.001) lowered. This effect lasted for at least 60 min and was not affected by
      the type of anesthetic used. Serum FSH levels were not affected by
      intracerebroventricular administration of RC-3095 or GRP (14-27), indicating
      different central control mechanisms between LH and FSH release. The suppressive
      effect of RC-3095 on LH release could be completely prevented by prior
      intracerebroventricular administration of GRP (14-27) at a dose of 1 micrograms,
      but intravenous administration of either peptide RC-3095 or GRP (14-27) did not
      change the basal levels of LH, FSH, and testosterone. The pituitary LH response
      to LH-releasing hormone was also not modified by intravenous administration of RC
      3095. These results indicate that bombesin-like peptides might be involved in
      control of LH release from the pituitary by an action on the CNS which is
      mediated by specific bombesin receptors.

PMID- 1369592
TI  - In vitro glucoregulation of prolactin secretion.
AB  - In this study we have examined the direct glucoregulation of prolactin secretion
      from normal anterior pituitary cells in vitro and have found that changes in
      medium glucose concentration regulate the amount of prolactin released. Nature
      and/or degree of this response to glucose was influenced by some effect, long
      lived in vitro, which was correlatable to serum insulin levels. When the cells
      were derived from animals with mean low-normal serum insulin levels, there was a
      stimulation of prolactin secretion by hypoglycemia, the response was rapid,
      transient, dose-dependent, and could be duplicated by 2-deoxyglucose. When the
      cells were derived from animals with a higher mean serum insulin level, the
      prolactin secretion from the cells was slowly, adversely affected by
      hypoglycemia. Conversely, elevated glucose caused a depression in prolactin
      secretion in the first group and a stimulation of prolactin secretion in the
      second. We conclude (1) that modulation of glucose levels in vitro regulates
      prolactin release from pituitary mammotrophs and (2) that this glucose regulation
      of prolactin release is in turn coregulated with or regulated by insulin.

PMID- 1369593
TI  - Glucocorticoid receptors in LHRH neurons.
AB  - Luteinizing hormone-releasing hormone (LHRH)-producing neurons constitute the
      final pathway for regulation of reproductive endocrine function by the central
      nervous system. Chronically elevated levels of glucocorticoids exert an
      inhibitory effect on reproductive function. Although this is thought to be
      mediated in part via modulation of classical transmitters and peptides which
      regulate LHRH synthesis and release, it is also possible that glucocorticoids may
      regulate LHRH neurons directly. We localized glucocorticoid receptors (GR) in
      LHRH neurons in the rat central nervous system using immunocytochemistry. In
      males and randomly cycling females 10-24% of LHRH neurons in the medial septum
      diagonal bands of Broca, and preoptic regions colocalized nuclear GR. Ovariectomy
      increased the percentage of GR/LHRH neurons at the level of the organum
      vasculosum of the lamina terminalis to 34%, half of which showed both nuclear and
      cytoplasmic GR. Treatment with estradiol reversed this effect. We suggest that
      the actions of glucocorticoids on reproductive endocrine function are mediated
      partly through direct modulation of LHRH gene expression and/or release by
      activated GR. Moreover, GR in LHRH neurons may provide a mechanism by which the
      gonadal steroid progesterone can affect LHRH neurons directly, despite a lack of
      progesterone receptors in these neurons.

PMID- 1369594
TI  - Histamine H1 and H2 receptor activation stimulates ACTH and beta-endorphin
      secretion by increasing corticotropin-releasing hormone in the hypophyseal portal
      blood.
AB  - Histamine (HA) stimulates the release of adrenocorticotropic hormone (ACTH) and
      beta-endorphin (beta-END) via activation of central postsynaptic H1 or H2
      receptors. The effect of HA is indirect and may involve the hypothalamic
      regulating factors corticotropin-releasing hormone (CRH), arginine vasopressin,
      or oxytocin (OT). We studied the effect of specific HA H1 or H2 receptor agonists
      on the concentration of CRH and OT in hypophyseal portal blood in urethane
      anesthetized male rats. In addition we investigated the effect of the agonists on
      ACTH and beta-END immunoreactivity in peripheral plasma in conscious male rats
      pretreated with antiserum to CRH. Intracerebroventricular administration of the
      H1 receptor agonist 2-thiazolylethylamine (2-TEA) or the H2 receptor agonist 4
      methylhistamine (4-MeHA) increased the CRH concentration in pituitary portal
      blood by 80-90% when compared to preinfusion levels (p < 0.05). Central infusion
      of saline had no effect. The level of OT in the pituitary portal blood was not
      affected by 2-TEA or 4-MeHA when compared to saline-treated rats.
      Intracerebroventricular infusion of 2-TEA or 4-MeHA increased the ACTH
      concentration in peripheral plasma 3- or 4-fold, respectively (p < 0.01).
      Pretreatment with a specific CRH antiserum (abCRH) inhibited the responses by 50
      and 70%, respectively (p < 0.01). Intracerebroventricular administration of 2-TEA
      or 4-MeHA increased the beta-END immunoreactivity in peripheral plasma 3- or 2
      fold, respectively (p < 0.01). These effects were inhibited by 80-90%, when rats
      were pretreated with abCRH (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369595
TI  - Immunocytochemical localization of insulin-like growth factor I in the
      hypothalamo-hypophyseal system of the adult rat.
AB  - Insulin-like growth factor I (IGF-I) is shown to be involved in the regulation of
      pituitary hormones. High IGF-I concentrations were detected in hypothalamus and
      pituitary during adulthood. This study was undertaken to analyze the cellular
      distribution of IGF-I in the hypothalamo-hypophyseal system of the adult rat
      using immunocytochemical procedures. IGF-I was found to be widely distributed
      throughout the hypothalamus; it was present in the magnocellular neurons of the
      supraoptic, paraventricular, and accessory nuclei. Moreover, nerve fibres and
      puncta containing immunoreactive IGF-I were localized in the median eminence and
      the posterior lobe of the pituitary. These results support possible IGF-I
      neuromodulatory or neurohormonal action in the hypothalamus on pituitary hormone
      regulation.

PMID- 1369596
TI  - Differential expression of melatonin receptors in spontaneously hypertensive
      rats.
AB  - Quantitative autoradiography was used to compare melatonin receptors in brain
      areas and arteries of young (4 weeks old) and adult (14 weeks old) spontaneously
      hypertensive rats (SHR) to those in age-matched normotensive controls, Wistar
      Kyoto (WKY) rats. Age and strain influenced the number of melatonin receptors in
      an anatomically selective manner, and the most striking changes occurred in
      arterial receptors. Melatonin receptors were not detectable in the anterior
      cerebral arteries of adult SHR. In the caudal artery, melatonin receptors
      decreased with age in both strains, but the decrease was more pronounced in SHR.
      When compared to age-matched WKY rats, the number of caudal artery receptors was
      higher in young and lower in adult SHR. The number of melatonin receptors was
      higher in the area postrema of adult SHR when compared to adult WKY rats, but in
      the suprachiasmatic nucleus, no such differences between the two strains were
      present. Alterations in receptor density were not accompanied by changes in
      binding affinity. Our results indicate that in the rat melatonin receptors show
      different developmental patterns according to location and that the receptors may
      be expressed differentially in genetic hypertension.

PMID- 1369597
TI  - Influence of dopamine on the altered release of prolactin, luteinizing hormone,
      and follicle-stimulating hormone induced by interleukin-2 in vitro.
AB  - Interleukin-2 (IL-2) alters the release of anterior pituitary hormones at
      femtomolar concentrations from hemipituitaries incubated in vitro. This cytokine
      significantly lowered luteinizing hormone (LH) and follicle-stimulating hormone
      (FSH) and stimulated prolactin (PRL) release, thus demonstrating a reciprocal
      action of the lymphokine on lactotrophs and gonadotrophs. Since dopamine (DA) is
      a powerful inhibitor of PRL release, in the present experiments were evaluated
      possible dose dependent effects of DA on IL-2-induced alterations of the release
      of PRL, LH, and FSH. Hemipituitaries were incubated with varying concentrations
      of DA, a combination of IL-2 plus DA, or a combination of haloperidol (1 x 10(-5)
      M) with DA for 1 h, followed subsequently by incubation with medium containing
      only high potassium (K+) to study the effects on depolarization-induced hormone
      release. DA induced a dose-related, significant lowering of the basal PRL release
      with a minimal effective dose (MED) of less than 19 nM. The depolarization
      induced PRL release was also inhibited, but the MED was 100-fold higher than the
      MED to inhibit basal PRL release. DA at much higher concentrations (30, 60, and
      90 microM) significantly reduced pituitary PRL content. The addition of 0.187,
      3.75, 15, or 60 microM DA to IL-2-induced PRL release. IL-2 (10(-15) M) produced
      a significant decrease in LH and FSH release. The combination of 3.75 or 15
      microM DA plus IL-2 failed to alter the IL-2 suppressed LH release, whereas the
      addition of 0.187 microM DA to IL-2 blocked its suppressive influence, and 60
      microM DA added to Il-2 produced an additive inhibitory effect. Thus, the
      interaction of IL-2 and DA is biphasic on LH release. The significant reduction
      of FSH release induced by IL-2 was blocked in the presence of 0.187, 3.75, 15, or
      60 microM DA. DA alone at relatively high concentrations of 30, 60, and 90 microM
      suppressed basal LH and FSH release. The effects of DA on PRL, LH, and FSH at all
      doses tested were blocked by the DA receptor blocker, haloperidol which by itself
      at the concentration tested (1 x 10(-5) M) had no effect. Thus, the actions of DA
      at all concentrations tested appear to be mediated via DA receptors. In
      conclusion, DA was capable of blocking the stimulatory action of IL-2 on PRL
      release and its inhibitory action on FSH release by a DA receptor mediated
      action.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1369598
TI  - Quantitative autoradiographic analyses of the time course and reversibility of
      corticosterone-induced decreases in binding at 5-HT1A receptors in rat forebrain.
AB  - Quantitative autoradiography was used to evaluate the time course and
      reversibility of corticosterone (CORT)-induced decreases in binding at 5-HT1A
      receptors in the dorsal hippocampus, cortex and septum of the male rat.
      Continuous exposure to high levels of CORT decreased binding of [3H]8-hydroxy-2
      (di-n-propylamino)tetralin at 5-HT1A receptors in the dentate gyrus and in the
      oriens and lacunosum moleculare layers of CA4 after 16 to 48 h. CORT-induced
      decreases in binding were also observed in the dorsal lateral septum after 2-4
      days, and in the intermediate lateral septum after 4-8 days of exposure to high
      levels of CORT. When CORT pellets that had remained in rats for 8 days were
      removed 3 weeks prior to sacrifice, binding at 5-HT1A receptors increased in
      comparison to control values in the oriens and lacunosum moleculare layers of
      CA2, and in layers 4-6 of the parietal/temporal cortex. These increases in
      binding were associated with very low serum CORT levels, and resembled increases
      previously observed in those areas in ADX rats. Although removal of CORT reversed
      the decreases in binding in the septum, no significant increases above control
      values were observed. Thus, there appear to be differences in the degree of
      sensitivity in the various brain regions to low and high levels of circulating
      adrenal steroids.

PMID- 1369599
TI  - Trophic effects of estradiol on fetal rat hypothalamic neurons.
AB  - Sex steroids play an important role in the development and functioning of the
      central nervous system (CNS); however, the mechanisms by which such hormones
      exert these effects are not well understood. We addressed the question as to
      whether sex steroids affect the development of the hypothalamus, at least in
      part, by acting as a trophic factor to modulate the number of neurons in the
      hypothalamus. To this end, primary hypothalamic cultures were prepared from the
      brains of embryonic (day 15) fetuses. Cultures received either 17 beta-estradiol
      (10(-12) M) or vehicle 6-h after seeding and everyday throughout the study. As
      early as 24 h later, cultures receiving 17 beta-estradiol had significantly more
      neurons (44%, p < 0.001) than the control cultures. This effect not only
      continued throughout the duration of the study, but the difference between the
      two groups increased so that after 5 days, 17 beta-estradiol-treated cultures had
      209% more neurons than control cultures (p < 0.001). Thus, addition of 17 beta
      estradiol to fetal hypothalamic cultures produced a significant increase in the
      number of neurons surviving in vitro. The presence of glia was not required for
      this phenomenon, since the number of neurons surviving in glial-free cultures was
      also significantly increased by the addition of 17 beta-estradiol. The neuron
      survival promoting effect of 17 beta-estradiol was saturable and could be blocked
      by the estrogen antagonist tamoxifen (10(-7) M). Testosterone (10(-10) M), but
      not the nonaromatizable androgen dihydrotestosterone (10(-10) M), could mimic the
      neuron survival-promoting effects of estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369600
TI  - Age- and sex-related changes in Tyr-MIF-1-like immunoreactivity in rat plasma.
AB  - The concentrations in plasma of the biologically active endogenous peptide Tyr
      MIF-1 (Tyr-Pro-Leu-Gly-NH2) have not been measured during development or in
      female rats. By radioimmunoassay, we found that Tyr-MIF-1-like immunoreactivity
      (Tyr-MIF-1-LI) was first consistently detectable in plasma when the rat was 5
      days old, and then gradually increased to adult concentrations by day 15. In male
      rats, the levels remained relatively constant for the next 21 months. In female
      rats, plasma concentrations of Tyr-MIF-1-LI at day 15 were about the same as in
      male rats. At 6 months of age, however, the concentrations in females decreased
      by half and by 21 months of life were only about a third of the concentrations
      found at day 15 or in age-matched males. The differences with age were not due to
      the length of time of storage of the samples, because another group of rats 1
      month old was killed on the same day as 5-day-old rats and still showed several
      times more Tyr-MIF-1-LI in the plasma; again, no differences were found between
      male and female rats at either 5 days or 1 month. A single injection of estradiol
      followed by progesterone lowered the concentrations in 1-month-old male rats. In
      female rats that were either ovariectomized or sham-ovariectomized, the expected
      similarity in their plasma concentrations of Tyr-MIF-1-LI was found at 1 month of
      age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369601
TI  - delta-Opioid receptors and the secretion of growth hormone in man: effect of
      opioid delta-receptor agonist deltorphin on GH responses to GH-releasing hormone
      and insulin-induced hypoglycemia.
AB  - To investigate the role of delta-opioid receptors in the modulation of growth
      hormone (GH) secretion, we compared in normal subjects the effect of the highly
      selective delta-opioid receptor agonist Deltorphin (DT) on the GH secretion
      responses to pituitary (GH-releasing hormone, GHRH)- and hypothalamic (insulin
      induced hypoglycemia, IIH)-mediated stimuli. DT blunted the GH response to IIH,
      whereas it had no effect on the GH response to GHRH. It is concluded that in man
      DT-induced activation of delta-opioid receptors exerts an inhibitory action on
      hypoglycemia-stimulated GH secretion. Based on the lack of an effect of DT on the
      GH response to GHRH, we suggest that DT may modulate the secretion of GH through
      suprapituitary mechanisms.

PMID- 1369602
TI  - Short-term starvation decreases POMC mRNA but does not alter GnRH mRNA in the
      brain of adult male rats.
AB  - Dietary restriction reduces circulating gonadotropin and testosterone levels in
      male rats, an effect thought to be mediated through reduced gonadotropin
      releasing hormone (GnRH) secretion; however, the cellular mechanisms subserving
      this response are still unknown. We reasoned that if dietary restriction reduces
      GnRH secretion, this would be reflected by a decrease in GnRH synthesis and
      likewise cellular GnRH mRNA levels. We tested this hypothesis by comparing
      cellular levels of GnRH mRNA between ad libitum fed (n = 4) and starved (n = 4)
      adult male rats. Five days of starvation resulted in a 21% decrease in body
      weight and an 85% decline in serum testosterone levels (fed: 13.9 +/- 2.00 vs.
      starved: 2.1 +/- 0.70 nmol/l; p < 0.01). In situ hybridization and image analysis
      demonstrated that short-term starvation influenced neither GnRH cell number (fed:
      148 +/- 16 vs. starved: 157 +/- 13 cells) nor cellular GnRH mRNA signal level
      (fed: 177 +/- 5 vs. starved: 160 +/- 7 grains/cell) in any region of the basal
      forebrain. Endogenous opioid peptides are known to exert an inhibitory effect on
      GnRH secretion and have been implicated in having a role in the starvation
      induced effects on the reproductive system. We therefore also tested the
      hypothesis that alterations in proopiomelanocortin (POMC) gene expression are
      involved in the neuroendocrine response to starvation, by comparing cellular POMC
      mRNA levels in individual neurons (approximately 160 neurons/animal) of the
      arcuate and periarcuate nuclei between fed control (n = 4) and starved (n = 4)
      adult male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369603
TI  - Estradiol enhances the action of neuropeptide Y on in vivo luteinizing hormone
      releasing hormone release in the ovariectomized rhesus monkey.
AB  - The effect of estrogen on the responsiveness of the luteinizing hormone-releasing
      hormone (LHRH) neurosecretory system to neuropeptide Y (NPY) stimulation was
      examined using a push-pull perfusion method in conscious monkeys. NPY, at doses
      of 10(-6) to 10(-12) M, was infused into the stalk-median eminence (S-ME) of
      ovariectomized monkeys with or without estrogen, while perfusates were
      continuously collected. LHRH in perfusates was measured by RIA. The results
      indicate that in both estrogen-primed and unprimed monkeys, NPY infusion into the
      S-ME elicited LHRH release in a dose-dependent manner (p < 0.01). Moreover,
      estrogen priming enhanced the responsiveness of LHRH release to NPY infusion: (1)
      the minimum NPY dose necessary to elicit a significant LHRH response was reduced,
      (2) the peak LHRH response to NPY at a dose of 10(-6) to 10(-10) M was increased,
      and (3) the total release of LHRH in response to NPY at doses of 10(-6) to 10(
      12) M was increased. These results suggest that NPY stimulates LHRH release in
      the S-ME in the presence or absence of estrogen and that estrogen enhances the
      responsiveness of the LHRH neurosecretory system to NPY stimulation in the rhesus
      monkey.

PMID- 1369604
TI  - Daily rhythm of aspartate aminopeptidase activity in the retina, pineal gland and
      occipital cortex of the rat.
AB  - The levels of specific soluble aspartyl aminopeptidase activity were assayed in
      retina, occipital cortex, anterior pituitary, posterior pituitary, pineal gland
      and serum of adult male rats, using Asp-2-naphthylamide as substrate, in a 12:12
      h light:dark cycle (7-19 h light). Significant diurnal variations appeared in
      retina, pineal gland, occipital cortex and serum. In addition, different patterns
      of diurnal variation of the enzymatic activity were observed in the tissues
      analyzed. A regular increase of the activity was noticed at the end of the dark
      period in all the tissues as a common feature, except in serum, in which the
      enzymatic activity reached a peak in the middle of the light period, decreasing
      progressively during the dark hours. After the last hours of darkness, the
      pattern of variation in the activity differed in each tissue. These diurnal
      variations in aspartyl aminopeptidase activity could reflect the functional
      status of its putative endogenous substrates, such as angiotensin II, and it may
      also suggest the existence of differential regulatory mechanisms associated with
      each location.

PMID- 1369605
TI  - Central administration of neuropeptide Y induces precocious puberty in female
      rats.
AB  - To examine the role of neuropeptide Y (NPY) in the regulation of puberty, the
      effects of various doses of NPY or saline injected into the 3rd ventricle of
      peripubertal female rats were determined. A single injection of NPY at a dose
      range of 10-20 micrograms into the 3rd ventricle of 30-day-old female rats
      advanced the time of vaginal opening (VO) and first ovulation by 4 days, as
      compared to saline-treated controls. Ova number and ovarian, adrenal and uterine
      weights at first estrous were similar in all animals regardless of treatment. The
      NPY-treated precocious animals showed lower body weight than did the VO-matched
      controls, but showed similar body weight as that of age-matched controls.
      Determination of plasma luteinizing hormone (LH) levels in the peripubertal
      female rats revealed that plasma LH was increased transiently immediately after
      NPY administration. Also, NPY-treated rats which had precocious puberty showed
      elevated pituitary and plasma LH levels on the day of VO. These results suggest
      that NPY can activate the hypothalamic-pituitary-gonadal axis to precociously
      initiate puberty.

PMID- 1369606
TI  - Increased circulating interleukin-1 and interleukin-6 after
      intracerebroventricular injection of lipopolysaccharide.
AB  - Recently, it was demonstrated that intracerebroventricular (icv) injection of
      interleukin-1 (IL-1) stimulated circulating interleukin-6 (IL-6) to a greater
      degree than intravenous (i.v.) injection of IL-1. The goal of this study was to
      compare the efficacy of lipopolysaccharide (LPS), injected both icv and i.v., on
      circulating concentrations of IL-1 and IL-6. Both i.v. and icv injection of LPS
      stimulated plasma levels of IL-1 to a similar degree. However, i.v. injection of
      LPS was significantly more efficacious than icv injection of LPS in elevating
      circulating IL-6. These results demonstrate that like i.v. injection of LPS, icv
      injection of LPS stimulates plasma levels of IL-1 and IL-6. Increases in
      circulating cytokines during infectious diseases which are limited to the central
      nervous system may serve to activate peripheral functions of an acute phase
      response.

PMID- 1369607
TI  - [A 28-year-old patient with hepatitis, parotid gland swelling, facial paralysis
      and conjunctivitis].

PMID- 1369608
TI  - [Retroperitoneal liposarcoma. Disclosure by anemia and prolonged fever].
AB  - We report the case of a 79-year old woman with a retroperitoneal liposarcoma. The
      condition was discovered because of the association, in a woman of that age, of
      anaemia and persistent fever. The diagnosis was suggested by computed tomography.
      Treatment was exclusively surgical. Liposarcomas usually affect men in their
      sixth decade. Postoperative radiotherapy improves the quality of life but does
      not prolong survival. Metastases are frequent, and death usually occurs in the
      year that follows discovery.

PMID- 1369609
TI  - [Cerebral toxoplasmosis concomitant with primary toxoplasma infection in AIDS].

PMID- 1369610
TI  - [Vesico-sphincteral rehabilitation in the elderly].

PMID- 1369611
TI  - [Epidemiologic study of myotonic dystrophy on the island of Mallorca].
AB  - Myotonic dystrophy (MD) or Steinert's disease is the most frequent hereditary
      myopathy in the adult. The aim of this study was to determine the rate of
      prevalence of MD on the island of Mallorca. Patients diagnosed with MD were
      studied in all public and private surgeries and centres able to diagnose this
      disease on the island of Mallorca. Therefore, this study included the whole
      population of Mallorca (551,129 inhabitants). A total of 60 cases were studied
      representing a prevalence rate of 110 cases per one million inhabitants. The
      patients were further classified according to the existence of family history and
      were geographically located into the different towns. The prevalence rate found
      was much higher than that described in the literature which oscillates between 30
      and 50 cases per million inhabitants. Furthermore, there was a concentration of
      cases in 10 of the 52 towns of the island with the presence of 2 cases in 6 being
      significant. The rate of prevalence of the disease in the city of Palma (295,136
      inhabitants) representing more than half of the population of the island was very
      similar (120 per million) to that found for the population as a whole.

PMID- 1369612
TI  - [Information and support to cancer patients. Experience from a course for young
      cancer patients at the Montebello Center].
AB  - The Montebello Centre offers courses for cancer patients from the whole country.
      The intention is to improve the patients' quality of life and ability to cope
      through information, group discussions and various kinds of activities. During
      Easter 1991 the Centre arranged a course for young people. An oncologist and a
      psychiatrist served as teachers and group participants, and offered individual
      consultations. Most of the patients had received insufficient information about
      their cancer. The period after end of active treatment was experienced as
      particularly distressing due to psychological reactions. The establishment of
      more self-help groups, and contact with already established groups, seem to be
      valuable psychosocial interventions.

PMID- 1369613
TI  - [Resources and possibilities for physiotherapeutic research?].

PMID- 1369614
TI  - Impact of the long term supply of iodized salt to the endemic goitre area.
AB  - The study was designed to assess the impact of the supplementation levels of
      iodine in salt supplied since the last 12 years to Gilgit and Hunza, an endemic
      goitre area of Pakistan. The overall prevalence of visible goitre is reduced from
      61.36% to 4.68%. Results of urinary excretion of iodine (UEI) indicate severe to
      mild iodine deficiency among 70.41% of the randomly surveyed households. Severely
      deficient are 3%, moderate 29.54% and mild 37.87%, criteria of UEI being less
      than 2.0 micrograms/dl, 2-5 micrograms/dl and 5-10 micrograms/dl respectively.
      Levels of iodine supplementation in 267 iodized salt samples at production (n =
      128) and consumption (n = 139) points are compared with a mean +/- SD are 70.86
      +/- 29.73 ppm and 37.24 +/- 20.47 ppm respectively, representing 566.8 +/- 237.8
      micrograms and 297.9 +/- 163.7 micrograms of iodine per 8.0 gram of salt. It is
      suggested to replace common salt with iodized salt in the goitre area to ensure
      the use by all households and quality control measures for iodination of salt
      should strictly be adhered so that uniform and consistent supply of iodine be
      ensured. The magnitude of contributory factors other than iodine deficiency,
      i.e., environmental and hereditary should be monitored and considered when levels
      of iodine supplementation are adjusted.

PMID- 1369615
TI  - [Use of the argon beam in laparoscopic surgery].

PMID- 1369616
TI  - [Sample size and publication of negative results].

PMID- 1369617
TI  - [How can we improve treatment of schizophrenia? Comments on the contribution by
      L. Ciompi, H.-P. Gauwalder, Ch. Maier and E. Aebi. The "Soteria Bern" pilot
      projects of treatment of acute schizophrenic patients].

PMID- 1369618
TI  - [Scullcap--liver damage. Mistletoe hepatitis].

PMID- 1369619
TI  - [Mucous membrane injuries associated with antiphlogistics--treatment and
      prevention].

PMID- 1369620
TI  - [Sudden cardiac death].

PMID- 1369621
TI  - [Respective role of high doses of immunoglobulins and plasma exchange in the
      treatment of Guillain-Barre syndrome].

PMID- 1369622
TI  - [Apropos of an accidental peridural injection].

PMID- 1369624
TI  - [Physician-patient relations].

PMID- 1369623
TI  - [Epidemiology of myotonic dystrophy in the island of Mallorca].

PMID- 1369626
TI  - Urological evaluation of sexual partners of women with human papillomavirus (HPV)
      infection.
AB  - Cancer of the uterine cervix has been related to HPV infection, based on clinical
      and laboratory data. The high recurrence rate in couples undergoing treatment for
      HPV infection points to a probable viral reservoir, either in subclinical lesions
      or in male internal genital organs. We have evaluated 31 men, all sexual partners
      of women with HPV infection. Eleven patients (35.5%) had related lesions: 4
      (12.9%) with condyloma acuminatum; 5 (16.1%) with lesions revealed by magnified
      examination after reaction with 5% acetic acid and 2 (6.5%) with condyloma and
      subclinical lesions. A short-term follow-up confirmed a successful treatment with
      podophyllin.

PMID- 1369625
TI  - Cerebral infarction in a girl who developed anticardiolipin syndrome after acute
      lymphoblastic leukemia.

PMID- 1369627
TI  - Four interfaces for liquid chromatography/atmospheric-pressure-ionization mass
      spectrometry.
AB  - Mixture analyses are demonstrated using the liquid chromatograph/atmospheric
      pressure-ionization mass spectrometric system with four modes. These modes are
      atmospheric-pressure spray with electron ionization, atmospheric-pressure
      chemical ionization, atmospheric-pressure spray ionization, and electrospray
      ionization modes. This system can deal with a wide variety of compounds from
      hydrocarbons with low polarity to proteins with high polarity.

PMID- 1369628
TI  - [Early diagnosis of breast cancer].

PMID- 1369629
TI  - [Invagination in children: a difficult diagnosis].

PMID- 1369630
TI  - [Systemic scleroderma and scleroderma-like disease after silicone implants].
AB  - Systemic sclerosis or clinical patterns indistinguishable from systemic sclerosis
      have previously been demonstrated in workers in the polyvinylchloride industry
      and in mine-workers exposed to silica dust. In recent years, an increasing number
      of cases of systemic sclerosis, localized scleroderma, and scleroderma-like
      disease have been diagnosed in women after implantation of silicone gel
      prosthesis either following operations for breast cancer or cosmetic augmentation
      mammoplasty. We present two cases of systemic sclerosis or scleroderma-like
      disease appearing after silicone implants. Together with the already reported
      cases these results should lead to reduced use of silicone for cosmetic
      augmentation mammoplasty and a search for another material for patients operated
      on for breast cancer. The cases described, together with the reports concerning
      industrially provoked scleroderma, are of interest for the continued efforts to
      clarify the pathogenesis of scleroderma. Other types of exposure than those
      described here may also be of interest, i.e. occupational exposure to silicone
      spray.

PMID- 1369631
TI  - [Treatment of hypertension in the elderly].

PMID- 1369632
TI  - [Norwegian physicians and referral to chiropractors].
AB  - Two comparable surveys were carried out, one in 1979 and one in 1989, to study
      the practice of medical practitioners as regards referrals to chiropractors.
      Norway is the only country where reimbursement for chiropractic treatment from
      the National Health Insurance depends on referral by a medical practitioner. The
      survey investigated the attitude towards this system of referral, whether or not
      a uniform standard of practice existed in regard to musculoskeletal disorders,
      and what types of conditions are referred. A substantial percentage, 41.6, of the
      patients had not been examined by their medical doctor before the referral, and
      23.9% had received their referral after the chiropractic treatment had started. A
      medical diagnosis was given in 84.3% of all cases, and x-ray findings were
      communicated to the chiropractors for 35.5% of the x-rayed patients. The surveys
      indicate that the present system of referrals does not function properly and may
      not be the best way of organizing the working relationship between medical
      doctors and chiropractors. The practice of referral had changed during the ten
      year period. In 1989, chiropractic was the first choice of treatment for patients
      with musculoskeletal problems more often than in 1979. Low back pain was the
      reason for the majority of referrals both in 1989 and in 1979. An apparent lack
      of standardization of diagnostic and therapeutic measures was demonstrated by
      comparing different regions of Norway. A marked discrepancy was found between
      rural and urban areas in the use of sick-leave and drug therapy.

PMID- 1369633
TI  - [New therapeutic methods in tubal pregnancy].
AB  - A world-wide increase in the incidence of extrauterine pregnancy has increased
      interest in new forms of treatment of this condition. In Denmark, the number of
      cases of diagnosed tubal pregnancies has doubled from 1980 til 1989. Experience
      with the spontaneous course of tubal pregnancies is reviewed. In addition,
      various forms of laparoscopic treatment and systemic and local treatment with
      methotrexate are described. In Denmark, local treatment with prostaglandin has
      been employed with good effect. Whether conservative surgical treatment or
      treatment with methotrexate or prostaglandin are to be employed depends upon the
      patience of the treating physician as regards control examinations with
      ultrasonic scanning and measurement of serum human chorion gonadotropin. Repeated
      tubal pregnancy in the salpinx involved, persisting trophoblastic tissue after
      treatment and long periods of observation are unintentional side effects of
      treatment. After conservative treatment of tubal pregnancy, it is important that
      the patient is given meticulous information.

PMID- 1369634
TI  - [To standardize the cardiologic language?].

PMID- 1369635
TI  - [Exploratory laparotomy in systemic mastocytosis].

PMID- 1369636
TI  - [Surgical gloves can cause serious problems].

PMID- 1369637
TI  - Protein A columns for the treatment of patients with idiopathic thrombocytopenic
      purpura and other indications.
AB  - ECI using protein A columns has been designed to selectively remove circulating
      CICs and IgG from the plasma of patients in whom these substances are associated
      with their disease. The use of protein A columns appears to be a reasonable
      alternative to plasmapheresis in many autoimmune disorders for which plasma
      exchange is indicated. Although preliminary evidence suggests efficacy of plasma
      exchange, there is a paucity of data indicating that ECI would indeed provide
      comparable efficacious results. Although the role of ECI using protein A columns
      for the treatment of ITP continues to be poorly defined, its use in urgent and
      life-threatening situations in both ITP and HUS appears reasonable. The results
      of any treatment for chronic refractory ITP continue to be unsatisfactory.
      However, favorable responses have been achieved using protein A columns,
      suggesting the need for further investigation. The role of ECI in the treatment
      of other disorders, including AIDS, TTP, and the treatment of malignancies, where
      clinical effects are transient, continues to be investigational. The true
      clinical response rates and duration of responses to ECI using protein A in
      treating any disorder requires definition in studies involving a larger number of
      patients with longer followup. The demonstration of the ultimate clinical value
      of this therapy will require clinical trials comparing its efficacy to other
      therapies. Although more serious reactions have been reported, toxicities
      associated with the use of protein A columns are generally transient and mild.

PMID- 1369638
TI  - Patient selection criteria for electrostimulation of salivary production in the
      treatment of xerostomia secondary to Sjogren's syndrome.
AB  - Electrostimulation has been introduced as a technique for increasing salivary
      output in the treatment of patients with xerostomia (dry mouth) secondary to
      Sjogren's syndrome. The procedure uses an electrostimulation device (salivation
      electrostimulator) to increase salivary production from existing glandular
      tissue. The device delivers a low-voltage electrical stimulus to the mouth via a
      probe. Patients with residual salivary tissue in the oral and pharyngeal regions
      who demonstrate a decrease in the flow rate of saliva are potential candidates
      for this procedure. It is estimated that more than one million people in the
      United States, predominantly middle-aged and elderly women, suffer from Sjogren's
      syndrome. Patients with chronic xerostomia complain of a continual feeling of
      oral dryness and have difficulty eating dry foods. These patients are susceptible
      to increased caries, oral pain, infection, and have difficulty speaking, chewing,
      and swallowing. The approach to the treatment of xerostomia in Sjogren's patients
      is usually determined by the level of severity of the symptoms. Appropriate
      management of patients with xerostomia requires that those patients whose
      salivary flow can be increased by means of sialagogues be distinguished from
      those patients whose salivary flow is either unaffected or insufficiently
      stimulated. To alleviate some of the complications due to salivary dysfunction in
      those patients who respond to stimuli, pharmacologic sialagogues as well as
      sialagogues that include sugarless gums, mints and candies are prescribed in
      order to increase salivary flow. Recently, electrostimulation via a hand-held
      stimulus probe has been introduced as a method of treatment in xerostomia
      secondary to Sjogren's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369639
TI  - Practice parameters for the assessment and treatment of attention-deficit
      hyperactivity disorder. American Academy of Child and Adolescent Psychiatry.

PMID- 1369640
TI  - Practice parameters for the assessment and treatment of conduct disorders.
      American Academy of Child and Adolescent Psychiatry.

PMID- 1369641
TI  - Cataract risk factors: blood level of antioxidative vitamins, reduced glutathione
      and malondialdehyde in cataractous patients.
AB  - Since many years experimental evidences have suggested an association between
      nutrition and lens opacities. A dietary deficiency of antioxidants and reactive
      oxygen scavengers may be involved in the pathogenesis of the "idiopathic" human
      senile cataract, as it has been demonstrated in some experimental cataracts. We
      tested the levels of ascorbic acid (vit. C), alpha-tocopherol (vit. E), reduced
      glutathione (GSH) and malondialdehyde (MDA) in the plasma or in the red blood
      cells (RBC) of 42 patients who were affected by surgically significant cataract
      and of 40 age-matched controls. Plasma vit. C mean level was 4.46 gamma/ml in
      cataracts and 4.62 gamma/ml in controls, while vit. E level was 7.70 and 7.09
      gamma/ml respectively. RBC GSH was found to be 342 gamma/ml in cataracts and 346
      in controls, while the MDA content was 4.06 picoMol/ml and 4.08 picoMol/ml
      respectively. The level of each tested nutrient or metabolite was not found to be
      statistically different between cataractous patients and controls, nor any
      significant trend was found to be present when the nutrients and metabolites were
      correlated to each other. Our results do not support the hypothesis of a
      nutritional deficiency in human senile cataracts. However, a defect in the
      antioxidative metabolism pathways could be present either systemically or at lens
      level.

PMID- 1369642
TI  - A nation-wide study of myopia prevalence in Israel. Findings in a population of
      312,149 young adults.
AB  - We conducted a nation-wide survey of the Prevalences of Myopia and other
      refractive errors in Israel, from data of medical examinations of an unselected
      population of 312,149 subjects ages 17 to 19 years. 80.47% of the population were
      emmetropic in both eyes. Myopia in both eyes was found in 16.27% of the
      population. The prevalence of monocular myopia was 1.69%. Manifest hyperopia in
      both eyes was found in 0.93% and astigmatism at least in one eye was found in
      7.13%. The various errors of refraction (myopia, hyperopia and astigmatism) were
      more common among females.

PMID- 1369643
TI  - Uveitis in patients with Graves' disease.
AB  - Uveitis was studied in patients with Graves' Disease. Graves' disease was found
      in 2.3% of uveitis patients, but no uveitis was found in patients with Graves'
      disease who visited our clinic with Graves' ophthalmology. Most of the Graves'
      disease patients with uveitis had had uncontrolled thyroid function before the
      onset of uveitis. Generally speaking, uveitis was mild. Steroid hormone therapy
      was very effective. No specific HLA type was found in our patients with uveitis.

PMID- 1369644
TI  - Effects of Nd-Yag laser vitreolysis on lens and vitreous prostaglandins in the
      rabbit eye.
AB  - This study concerns the quantitative modifications of the prostaglandins, PGF
      alpha e PGE2, in the vitreous and in the lens following the application of Nd-Yag
      Laser. Five minutes after the Yag-laser treatment, an increase of PGF1 alpha
      concentration of PGE2 decreased in the lens and increased in the vitreous. These
      changes, similar to those occurring in the aqueous humor, may be related to the
      activation of specific enzymatic pathways of prostaglandin synthesis.

PMID- 1369645
TI  - Morphology of the transplantable colon carcinoma derived from the spontaneous
      colon carcinoma of WF-Osaka rat strain.
AB  - Two lines of the transplantable colon carcinoma were established. They were from
      the spontaneous colon carcinoma of WF-Osaka rat strain which had been set up in
      our laboratory. Transplant procedure was carried out mainly by the
      intraperitoneal implantation, and, in particular, the treating with a specified
      way of HIBITANE for disinfection against colonic flora at the primary transplant
      was quite effective. The growth speed of the transplanted colon carcinoma was
      slow at first and gradually increased its speed. Histology of the transplanted
      tumor altered gradually from the glandular pattern at first to the medullary
      pattern in the late stage of the transplant generation. Each tumor node in the
      late stage of transplant generation was composed of numerous small nodules
      separated by thin stromal tissue. Squamous metaplasia and central necrosis were
      seen in the center of the small nodules. Two lines of the transplantable colon
      carcinoma were named C1 and C2 and the former is at now the 101th generation and
      the latter is at the 107th generation.

PMID- 1369646
TI  - Interaction of zonisamide with benzodiazepine and GABA receptors in rat brain.
AB  - The effects of zonisamide on [3H]flunitrazepam binding and [3H]muscimol binding
      were studied in Sprague-Dawley rat brain. Specific [3H]flunitrazepam bound was
      decreased to 64.6 +/- 5.6% (mean +/- SD, n = 5, p < 0.002) and 91.9 +/- 4.0% (p <
      0.005) by the addition of 10(-3) M and 10(-4) M zonisamide, respectively.
      Scatchard plot analysis of [3H]flunitrazepam binding with 10(-3) M of zonisamide
      revealed an increased Kd value with no change in Bmax. No inhibitory effect of
      zonisamide was seen on the enhancement of specific [3H]flunitrazepam binding by
      GABA. As for the effects on GABA receptors, specific [3H]muscimol bound was
      decreased to 27.7 +/- 10.4% (mean +/- SD, n = 4, p < 0.005) and 68.3 +/- 3.7%
      (mean +/- SD, n = 4, p < 0.005) by the addition of 10(-3) M and 10(-4) M
      zonisamide, respectively. Since therapeutic serum level of zonisamide are around
      10(-4) M, these results suggest that zonisamide neuropharmacologically interacts
      with the GABA/benzodiazepine receptor ionophore complex in a manner similar to
      phenytoin.

PMID- 1369647
TI  - [3H]zonisamide binding in rat brain.
AB  - We previously reported that zonisamide inhibits both [3H]flunitrazepam and
      [3H]muscimol binding in rat brain. In the present study, [3H]zonisamide was found
      to bind in a saturable fashion to the crude synaptosomal fraction of whole rat
      brain. Linear regression analysis of the binding data in the Scatchard plot
      indicated a Kd of 90 nM, and a maximal binding capacity of 1.40 x 10(3) fmol/mg
      protein. Displacement studies revealed an inhibitory effect of clonazepam and an
      enhancement effect of GABA on specific [3H]zonisamide binding. These results
      suggest that specific [3H]zonisamide binding sites may have a tight
      correlationship with benzodiazepine receptors in rat brain.

PMID- 1369648
TI  - The CT evaluation of transcatheter arterial chemo-embolization, using iodized oil
      for hepatocellular carcinoma.

PMID- 1369649
TI  - Polymorphonuclear leukocyte induced vasoconstriction in isolated canine coronary
      arteries.
AB  - To assess how polymorphonuclear leukocytes act on coronary vasomotion, we
      measured the changes in isometric tension of isolated canine coronary arterial
      rings by adding autologous polymorphonuclear leukocytes to the organ chamber.
      Ring preparations of the left circumflex coronary artery developed isometric
      tension with a maximum of 80 +/- 21% of PGF2 alpha (5 muM)-induced contraction at
      the addition of polymorphonuclear leukocytes (5 x 10(5) cells/ml) isolated by the
      Percoll gradient method. This increase in tension was dependent on the amount of
      added polymorphonuclear leukocytes (10(4)-5 x 10(6) cells/ml). The integrity of
      endothelial cells was not disrupted after the addition of polymorphonuclear
      leukocytes, because the developed tension was reversed by the addition of
      acetylcholine in an endothelium-dependent manner. The mechanical rubbing of
      endothelium completely abolished this polymorphonuclear leukocyte-induced
      vasoconstriction, which was regained by placing an endothelium-unrubbed ring
      inside the rubbed ring ("sandwich preparation"). The supernatant of either
      polymorphonuclear leukocyte suspension or polymorphonuclear leukocyte incubation
      medium with A23187 could not induce the development of vascular tension.
      Lipoxygenase inhibitors partially suppressed polymorphonuclear leukocyte-induced
      vasoconstriction. These findings indicate that polymorphonuclear leukocytes and
      endothelial cells. This polymorphonuclear leukocyte-induced vasoconstriction is
      not an increase in resting tension due to endothelial injury caused by added
      polymorphonuclear leukocytes, but the development of active tension. Lipoxygenase
      product(s) of arachidonate may partially mediate this contraction.

PMID- 1369650
TI  - Adenocarcinoma in the ascending colon of ACI strain rat foster bred by WF-Osaka
      female rat.
AB  - We now keep HFRSV free WF-Osaka rats and ACI rats together in the separate three
      animal rooms (animal room 1, 2 and 3) and the incidence of colon carcinoma is
      still high on the WF-Osaka rats in animal room 1 with the high humidity. Two
      female ACI rats developed colon carcinomas in the ascending colon. The gross and
      the histological appearance of the colon carcinoma were completely the same as
      those of WF-Osaka rats. ACI and WF-Osaka rat strain together have been kept bred
      in neighborhood of each other in different racks in the identical animal room 1.
      To obtain HFRSV free ACI rat strain, Antecedents born by cesarean section of ACI
      female pregnant rat were foster-bred by WF-Osaka female nursing rat incidentally,
      and at the fourth mating generation after the start of foster-breeding, they
      developed colon carcinomas at the age of four months. Before five out of eight F1
      hybrids by WF-Osaka cancer carrying female rat x male ACI rat had developed the
      same colon carcinoma, but none of F1 hybrids by the contrary mating had developed
      colon carcinomas in this same animal room 1. Animal room 1 and 2 where there was
      a high incidence of colon carcinomas, had happened to be kept moistened. However,
      after disinfection of these animal rooms, the animal room 2 and 3 occurred to be
      kept dried, and rats of WF-Osaka strain ceased to develop colon carcinomas in the
      animal room 2. Thereafter, animal room 2 and 3 were adjusted to be kept moistened
      again. Subsequently WF-Osaka rats in the animal room 2 began to have colon
      carcinomas in the ascending colon as before, but none of rats developed colon
      carcinomas in the animal room 3. Based on these findings, we consider that milk
      factor at the time of foster-breeding played an important role first and high
      moistened condition of the animal room resulted in promoting effect on colon
      carcinogenesis on ACI rats and WF-Osaka rats as well.

PMID- 1369652
TI  - In vivo evaluation of fixation of metal implants coated by melt-sprayed alumina-
      experiments in rabbit.
AB  - Skeletal fixation characteristics of the stainless steel implants coated by 60
      microns thick porous alumina layer using a flame spray method were evaluated in
      vivo for the duration of up to 12 weeks. Surface roughness of the implants
      appeared to be the determining factor for the fixation characteristics,
      irrespective of the implant materials.

PMID- 1369651
TI  - Initial appearance of an ill-defined shadow on a chest roentgenogram in a patient
      with aortitis syndrome.
AB  - A 20-years-old woman with fever and an abnormal shadow on a chest roentgenogram
      was admitted to our hospital. High grade fever continued even after gradual
      disappearance of the ill-defined shadow on the right upper lobe (S3) with minor
      fissure deviation upward, while neck pain and bruit gradually developed. She was
      diagnosed as aortitis syndrome from a digital subtraction angiography. The
      initial appearance of an ill-defined shadow on a chest roentgenogram, considered
      as pulmonary infarction, is rare in the aortitis syndrome and this kind of onset
      is interesting in relation to the pathogenesis and diagnosis of this syndrome.

PMID- 1369653
TI  - Prediction of contractile reversibility in impaired left ventricular wall motion
      following coronary artery bypass grafting.
AB  - Interventional left vertriculograms (LVGs) using postextrasystolic potentiation
      (PESP), nitroglycerin (TNG) and a combination of both were analyzed in order to
      decide the degree of efficacy of each intervention as a predictor of
      reversibility in impaired left ventricular segments. Segmental wall motion (SWM)
      in less severely impaired segments increased to the normal range and SWM in
      severely impaired segments increased but remained in the abnormal range after
      CABG. The effects of both PESP and TNG on SWM in impaired segments correlated (r
      = 0.78 and 0.78) with that of CABG. The increase in SWM due to TNG + PESP was
      significantly (p < 0.01) greater than that due to either PESP or TNG alone or
      that of CABG. Either PESP or TNG was clinically reliable for prediction of
      contractile reversibility in the segments with impaired wall motion prior to
      CABG. Including the global left ventricular function, PESP reflected the efficacy
      of CABG more sufficiently than TNG. TNG + PESP provoked more contractile reserve
      and exaggerated the results of CABG, but may predict reversibility in severely
      reduced wall motion.

PMID- 1369654
TI  - Ultrasonographic monitoring of pancreatic pseudocyst during delivery.
AB  - A case of pancreatic pseudocyst complicating with pregnancy and delivery was
      reported. This primipara patient with pancreatic pseudocyst was able to achieve a
      full-term, transvaginal delivery of a mature baby. The usefulness of ultrasonic
      monitoring of the pseudocyst during labor was clinically demonstrated. When intra
      abdominal pressure increased, pancreatic pseudocyst was deformed.

PMID- 1369655
TI  - Effects of injection interval on pentylenetetrazol (PTZ) kindled seizures in
      rats.
AB  - We investigated the effects of different injection intervals, (24 hr, 48 hr, and
      72 hr) on the development of kindled seizures induced by repetitive
      pentylenetetrazol (PTZ) injections (30 mg/kg) in rats. Regardless of injection
      interval, kindled seizures were obtained 1 week after the completion of
      consecutive PTZ injections. This PTZ kindled seizure model appears to mimick
      generalized seizure and be useful in the investigation of seizure phenomenon.
      With 48 and 72 hr injection interval, the seizure responses gradually increased
      with consecutive injections. The convulsive severity of 24 hr interval group
      showed a transient increased and then stabilized at a low score (2/6). This
      difference between these injection interval might reflect the appearance of some
      short of inhibition during the more closely spaced (24 hr) repeated injections.

PMID- 1369656
TI  - Induced adenocarcinoma of the ascending colon on LE and Wistar/Shhi rats and
      virus like particles in the serum of colon cancer carrying WF rats.
AB  - Intraperitoneal injection of the serum of colon cancer carrying WF rats induced,
      within two months, colon carcinomas in the ascending colon of LE and Wistar/Shi
      rats when they were given it during their suckling. We had also induced colon
      carcinomas in the ascending colon of ACI rats by the same methods. Therefore, it
      is supported that this serum derived from colon cancer carrying WF rats must have
      some transmissible agent in itself. In addition, we ultracentrifuged the serum of
      cancer carrying WF rats and we found, in the sediment, numerous round or oval
      virus like corpuscles by electron microscopy studies. Negatively stained
      corpuscles by phosphotungstic acid staining clearly revealed fine spike
      appearance on their surface. We believe that these virus like corpuscles are the
      etiological agent for the transmissible colon carcinoma of WF rat strain.

PMID- 1369657
TI  - Histopathology of the temporal bones in thanatophoric dysplasia.
AB  - The pathological findings of temporal bone in two cases of thanatophoric
      dysplasia were reported. Thanatophoric dysplasia is classified into type 1 and
      type 2, each of which has been reported to show specific clinical and
      radiographic-findings. The present study revealed that each type also showed
      specific characteristic in the structure of the temporal bones. The developmental
      mechanisms of hearing impairment in this disease were also discussed on the basis
      of the pertinent literature.

PMID- 1369658
TI  - Recurrence after incompletely resected acousticus neurinomas.
AB  - It is known that the recurrence rate is high when an acoustic neurinoma is
      incompletely excised, but the details of the process of recurrence are still
      unclear. We reviewed the recurrence of acoustic neurinomas, as evaluated by
      computed tomography (CT) or magnetic resonance imaging (MRI), in 51 consecutive
      patients over the past 10 years who underwent tumor resection and had
      postoperative follow-up by CT or MRI. The factors promoting recurrence related to
      incomplete excision of tumor were analyzed. Total resection of the tumor was
      performed in 22 patients (43%), nearly total resection in 17 patients (33%) and
      subtotal resection in 12 patients (24%). The recurrence rates were 29% (5 of 17
      patients) and 25% (2 of 8 patients) for nearly total and subtotal resection,
      respectively, whereas no recurrence occurred following total resection. Of the
      patients having nearly total resection, all recurrences arose from residual tumor
      in the internal auditory meatus (5 of 12 patients). In contrast, there were no
      recurrences from residual tumor at the site of the brain stem (none of 4
      patients). Acoustic neurinomas should be totally removed through neurosurgical
      and neuro-otological approaches whenever possible. If a small fragment of tumor
      is left in the internal auditory meatus due to fear of damaging the facial or
      cochlear nerves, it should be strictly followed up by CT or MRI.

PMID- 1369659
TI  - Demonstration of islet cell antibodies in apparently non-insulin dependent
      diabetic patients; a marker for the later development of insulin dependency.
AB  - One hundred and ten diabetic patients who were apparently non-insulin dependent
      at 1984 were followed up for 5 years from 1984 to 1989. Islet cell antibodies
      (ICA) of the patients were tested in 1987. Eleven patients were positive for ICA
      and 99 were negative. There was no significant difference in age, sex, duration
      of diabetes, and HbA1c levels between ICA-positive and negative groups. Six of 11
      (54.5%) patients in ICA-positive group developed insulin-requiring state in the
      period from 1984 to 1989, while only 5 of 99 (5.1%) patients in ICA negative
      group became insulin-requiring. Glucagon tolerance test (1 mg i.v.) was performed
      on 8 patients who developed insulin-requiring state; among them 4 patients were
      ICA-positive and other 4 patients were ICA negative. The serum C-peptide response
      to intravenous glucagon injection was markedly decreased in 3 of the 4 ICA
      positive patients, and only mildly decreased in all the 4 ICA-negative patients.
      The markedly decreased C-peptide response indicates that these ICA-positive
      subjects had developed insulin-dependency. We conclude that the presence of ICA
      in apparently non-insulin dependent diabetics indicates a high risk for
      developing insulin-dependency.

PMID- 1369661
TI  - Proceedings of the 1990 International Drug Discrimination Symposium.
      Noordwijkerhout, the Netherlands, June 25-27, 1990.

PMID- 1369660
TI  - Clinical and histologic study of endoscopic duodenitis.
AB  - Duodenitis was investigated by endoscopy in 93 cases from among 1242 subjects.
      Endoscopic duodenitis was classified into three types endoscopically--reddening
      type, erosive type and nodular type. There was a relatively high correlation
      between the endoscopic and the histological diagnosis of duodenitis. Severely
      inflamed cases were found histologically more frequently in erosive- or nodular
      type duodenitis than in reddening-type duodenitis. During the follow-up period,
      changes in endoscopic findings were observed more frequently, from the erosive
      type to the reddening type, and from the reddening type to normal. There were no
      cases which subsequently developed duodenal ulcers. We found a significantly high
      incidence of "endoscopic duodenitis" in uremic patients who had been given
      regular dialysis, and not in hepatic cirrhosis patients.

PMID- 1369662
TI  - Discriminative stimulus properties of nicotine: mechanisms of transduction.
AB  - Our thinking about how nicotine might be inducing DS control of behavior has
      changed drastically in the past 25 years. Our first inclination was that nicotine
      was mimicking ACh at a variety of specific and select n-AChRs. Then several
      nicotine researchers suggested that nicotine might be acting via specific and
      select noncholinergic receptors. At present, we seem to have returned to the view
      that nicotine may have pronounced effects at the n-AChR (figure 1), at least in
      some specific cases such as in the development of tolerance and in rats trained
      to discriminate nicotine (figure 6). The endogenous ligand has not changed, but
      the mechanism of how it affects presynaptic and postsynaptic receptors appears to
      have been rediscovered. The concept of rapid ACh-induced desensitization at the n
      AChR is not new and appears basic to cholinergic neuronal function (figure 5).
      The desensitization concept has been revitalized by several investigators who
      also consider this mechanism important to how nicotine might act in protecting DA
      neurons from neurotoxicity of chemicals such as 6-OHDA or MPTP (Janson et al.
      1988). The overall concept suggests that n-AChR desensitization at presynaptic DA
      sites may reduce neuronal accessibility to select exogenous neurotoxins and thus
      attenuate neuronal destruction. This hypothesis has also been partially validated
      in relation to the cholinergic neuron by providing preliminary evidence that
      nicotine was able to reduce cholinergic neuron destruction (measured by brain ACh
      levels) via the intraventricular administration of the neurotoxin AF64A, an ACh
      nitrogen mustard (Villanueva et al. 1990). Thus, nicotine or compounds acting
      like nicotine could possibly be beneficial to patients exhibiting the select
      neurological problems observed in Parkinson's and Alzheimer's diseases. The
      process of desensitization might also be useful to understanding why humans
      choose to smoke tobacco products. Perhaps the ability of nicotine to induce such
      neuronal effects at a specific n-AChR makes it reinforcing (or aversive) to
      behavior. Such a mechanism of action might explain why nicotine appears to both
      increase and decrease arousal levels in animals (or humans) exhibiting
      differential basal level of excitability (Hendry and Rosecrans 1982), or why some
      people never become dependent on nicotine. How nicotine alters the n-AChR may
      also be beneficial to our understanding of the subtle nature of cholinergic
      neuronal function in learning, memory, and other behavioral states. The ability
      of ACh (or nicotine) to induce an activation or attenuation of some cholinergic
      or noncholinergic neuron or both may be important to these brain
      processes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1369663
TI  - Discriminative stimulus properties of benzodiazepines and several new
      anxiolytics.

PMID- 1369664
TI  - Distinctive discriminative effects of ethanol.

PMID- 1369665
TI  - Training dose: influences in opioid drug discrimination.

PMID- 1369666
TI  - Discriminative stimulus properties of phencyclidine and other NMDA antagonists.

PMID- 1369667
TI  - Discriminative stimulus effects of psychomotor stimulants and benzodiazepines in
      humans.

PMID- 1369668
TI  - Tolerance to drugs acting as discriminative stimuli.
AB  - The experiments described above highlight the ways behavioral and pharmacodynamic
      processes interact to modulate the development of tolerance to the discriminative
      stimulus effects of drugs. These studies suggest that frequent drug exposure does
      not lead inevitably to the development of tolerance to a drug's discriminative
      effects. Rather, the interplay between a drug stimulus and reinforcement
      opportunities shapes the sensitivity of discriminative performances over
      successive episodes of drug exposure. Maintaining a discriminative relation
      between a drug and behavior strengthens the likelihood that an initially
      effective dose will maintain discriminative control. Development of tolerance
      requires exposure to both treatment regimens appropriate to the agent under study
      and behavioral contingencies that limit an individual's ability to learn a new
      discrimination. When both requirements are met, tolerance does develop to drugs
      acting as discriminative stimuli. When training is suspended during a period of
      chronic drug treatment, the dose of drug required to evoke stimulus control can
      be increased by treatment with appropriate maintenance doses of the training drug
      or a closely related drug. Tolerance is proportional to maintenance dose,
      develops relatively slowly, and disappears after termination of repeated drug
      treatment. Tolerance appears pharmacologically specific and can be accompanied by
      cross-tolerance to other drugs that evoke cross-generalization with the training
      drug. Finally, tolerance can be diminished markedly by continuing training with
      the original training dose. Taken together, these patterns suggest that
      development of tolerance to drugs acting as discriminative stimuli is the result
      of joint actions of conditioning and pharmacodynamic processes.

PMID- 1369669
TI  - Tolerance: role of conditioning processes.

PMID- 1369670
TI  - Responding to drug-related stimuli in humans as a function of drug-use history.

PMID- 1369671
TI  - State dependency as a mechanism of central nervous system drug action.

PMID- 1369672
TI  - Discriminative stimulus properties of hallucinogens and related designer drugs.
AB  - Animals trained to discriminate classical hallucinogens from saline have been
      used in the past decade to examine other hallucinogenic agents. Time course
      (onset, duration of action) and locus of action have been studied, SARs have been
      formulated, and mechanism of action has been investigated in detail. On the basis
      of DD studies in animals, it was proposed that hallucinogenic agents may produce
      their actions in humans via a 5-HT2 agonist mechanism and that certain
      phenalkylamine hallucinogens such as DOM and DOB might constitute the first known
      examples of 5-HT2 agonists. This led to the development of [3]HDOB and [125I]DOI
      for use in radioligand binding and autoradiographic studies and to the use of
      hallucinogen-trained animals as a functional behavioral model of 5-HT2 receptor
      activation. Animals trained to classical hallucinogens are more recently being
      used to evaluate novel designer drugs. It can be seen, then, that this paradigm,
      using hallucinogenic agents as training drugs, has proven to be quite useful for
      the investigation of hallucinogens and nonhallucinogens alike.

PMID- 1369673
TI  - State-dependent learning with social drugs.

PMID- 1369674
TI  - Discriminative stimulus effects of drug mixtures in rats.

PMID- 1369675
TI  - Application of drug discrimination with drugs of abuse to develop new therapeutic
      agents.

PMID- 1369676
TI  - Intracranial stimulation as reinforcer for neuropeptide discrimination.

PMID- 1369678
TI  - Schedule-induced self-injection of drugs.

PMID- 1369677
TI  - Drug discrimination used to study drug withdrawal.

PMID- 1369680
TI  - Discriminative stimulus properties of amphetamine, cathinone, and related agents.
AB  - Although the AMPH and CATH cues have been studied extensively, inconsistent
      findings remain that need to be investigated. It is not known to what extent, if
      at all, AMPH and CATH cues differ and how they differ from the cocaine cue. The
      extent to which D1 and D2 receptor systems are coupled in AMPH DD assays requires
      further investigation. The inconsistent findings in substitution studies with
      nisoxetine need to be addressed in parametric studies in various species.
      Finally, the possibility that the AMPH cue may generate false positives in
      screening for drug abuse potential needs to be evaluated.

PMID- 1369679
TI  - Use of drug discrimination in drug abuse research.

PMID- 1369681
TI  - A historical perspective on drug discrimination.

PMID- 1369683
TI  - Discriminative stimulus functions of cannabinoids/cannabimimetics.

PMID- 1369682
TI  - Discriminative stimulus effects of cocaine.

PMID- 1369685
TI  - Patient treatment compliance in leprosy; a critical review.

PMID- 1369684
TI  - Neurite growth-promoting protein (amphoterin, p30) binds syndecan.
AB  - A new ligand for syndecan (a cell surface heparan sulfate-rich proteoglycan) has
      been discovered. In the solid-phase binding assay utilizing small nitrocellulose
      discs to immobilize matrix molecules, binding of syndecan to neurite growth
      promoting protein, p30/amphoterin, was observed. This binding was strongly
      dependent on the concentration of amphoterin used to coat the discs, but was
      saturable with an excess amount of syndecan. The interaction was inhibitable with
      heparan sulfate and heparin but less effectively with chondroitin sulfate,
      indicating that heparan sulfate chains of syndecan were involved in the binding.
      Anti-amphoterin antibodies inhibited the binding partially. Mouse mammary
      epithelial cells were shown to bind amphoterin directly but not after trypsin
      treatment or in the presence of heparin and to produce amphoterin in the
      extracellular space. Both syndecan and amphoterin were found to localize on
      lateral surfaces of newly adhered mammary epithelial cells. Toward confluency
      amphoterin amounts decreased. Because amphoterin can be localized to the same
      sites with syndecan and because of their interaction, amphoterin is a new
      putative pericellular ligand for syndecan. These interactions may be involved in
      the regulation of cell behavior.

PMID- 1369686
TI  - Virostatic in vivo effect of elliptinium on Friend's retrovirus (a model for HIV
      infection).
AB  - As we had discovered the virostatic effects of some analogues of acriflavine, a
      non-oncostatic intercalating agent, on HIV1 and on its best murine model,
      Friend's virus [7], we then studied other non- or poorly oncostatic intercalating
      agents, in particular ellipticins (whose negligible cytostatic effect with
      methoxy-9-ellipticin we first published. We report in this paper the in vivo
      virostatic effect of 2-methyl-9-hydroxy-ellipticinium (elliptinium) on Friend's
      virus.

PMID- 1369687
TI  - In vitro immunomodulatory effects of traditional Kampo medicine (sho-saiko-to:
      SST) on peripheral mononuclear cells in patients with AIDS.

PMID- 1369688
TI  - Ethambutol in tuberculosis.
AB  - Ethambutol gained rapid acceptance as a substitute for PAS in tuberculosis
      therapy because of improved patient tolerance and convenience of administration.
      Ocular toxicity was recognized early on but was thought to be a problem only at
      higher dosages. There have, however, been a number of reports of serious visual
      impairment on conventional dosage, with permanent blindness in some cases, and
      painfully slow recovery in others. The precise mechanism for the optic neuritis
      is not clear, and toxicity is difficult to predict in the individual patient.
      Ethambutol appears to contribute only marginally to modern short course regimens
      and should be replaced with a less toxic agent.

PMID- 1369689
TI  - Growth factors and oncogenes in human solid tumors: clinical aspects.
AB  - Growth factors, growth factor receptors and oncogenes have been extensively
      studied in human tumors for some years. The purpose of this paper is to review
      the clinical results obtained in human cancers and their predisposing conditions
      or high risk groups as well as their relation with clinical, pathological
      characteristics and their prognosis.

PMID- 1369690
TI  - Isolation and characterization of VP-16 resistant human leukemia cell line.
AB  - VP-16 resistant cells, designated VP-16K6-1 (K6-1) were isolated from human acute
      lymphoblastic leukemia cell line RPMI 8402. IC50 value against VP-16 were 11-fold
      higher than their sensitive parental cell line. The membrane permeability of the
      drug was not responsible for resistance in K6-1 cells. K6-1 cells showed
      resistance in drug-induced DNA strand breaks (single strand breaks) determined by
      the alkaline sucrose gradient sedimentation method. Dot-blot analysis of RNA
      extracted from 2 cell lines showed that the mRNA levels of DNA topoisomerase II
      in K6-1 cells decreased slightly compared with that of parent cells. However,
      Topo II activities were similar in wild-type and K6-1 cells. In addition, K6-1
      cells exhibited cross-resistance only to VM-26. These data suggest that a reduced
      intracellular Topo II level may contribute to drug resistance as an important
      factor in K6-1 cells.

PMID- 1369691
TI  - Reduced DNA topoisomerase II in VP-16 resistant mouse breast cancer cell line.
AB  - VP-16 resistant cells, FvprB350 (50B-3), were isolated from mouse breast cancer
      cell line FM3A. 50B-3 cells showed 84-fold higher resistance than their parent
      cells. Reduced drug uptake was not found in resistant cells. Quantitative
      analysis of drug-stimulated DNA cleavage activity using 3'32P end-labeled pBR322
      restriction fragments showed that VP-16 stimulated DNA-topoisomerase II cleavable
      complex forming activity in crude nuclear extract from 50B-3 cells was
      approximately one-fifth as compared with that of FM3A wild-type cells. Dot-blot
      analysis of RNA extracted from the two cell lines showed that mRNA levels of
      topoisomerase II in 50B-3 cells drastically decreased and catalytic activity was
      also 1/2-1/3 as compared with that of parent cells. 50B-3 cells showed cross
      resistance to VM-26, m-AMSA, adriamycin. These findings suggest that reduced
      topoisomerase II activity (cellular levels) and cleavable complex forming
      activity may be significant factors in the marked drug resistance.

PMID- 1369692
TI  - Glucose metabolism and beta receptor function in atopic asthmatics.
AB  - Severe asthma and diabetes have been reported not to co-exist in the same
      patient. Various studies have attributed this to the possible association of
      asthma with hyperinsulinism, increased responsiveness to insulin or to beta
      blockade. Previous studies have not addressed all these possible mechanisms in
      the same patient. In this prospective study, 7 atopic asthmatics and 7 age and
      sex-matched healthy controls underwent glucose, insulin and glucagon tolerance
      tests. The results showed no evidence of hyperinsulinism or increased
      responsiveness to insulin. Intravenous administration of glucagon, however,
      showed a lesser increase of glucose and insulin in asthmatics. Since glucagon has
      a beta-agonist effect on the liver and activates glycogenolysis and
      gluconeogenesis via beta-receptor stimulation and stimulates insulin secretion by
      activating adenylate cyclase of pancreatic beta-cells through beta-receptors, the
      results of glucagon tolerance test in our study may therefore suggest the
      presence of partial beta-blockade in atopic asthmatics.

PMID- 1369693
TI  - Biologic activities of HIV-1 envelope glycoprotein: the effects of crosslinking.
AB  - We have examined the biologic activities of native and recombinant preparations
      of human immunodeficiency virus envelope glycoprotein (gp120), both derived from
      the HIV-1B strain. Antibody to gp120 was used to evaluate the effects of
      crosslinking gp120 on signalling by the CD4 receptor. Our results indicate that
      native and recombinant gp120 produce identical effects in our assay systems.
      Crosslinking gp120 amplified its chemoattractant activity for lymphocytes and
      monocytes and increased the peak intracellular calcium level, compared with
      binding of gp120 alone. The induction of inositol trisphosphate (IP3) production,
      induction of interleukin 2 receptors (IL2R), and inhibition of lymphocyte
      proliferation following treatment with gp120 were not enhanced by the addition of
      crosslinking antibody.

PMID- 1369694
TI  - T lymphocyte subsets in chronic uremic patients treated with maintenance
      hemodialysis.
AB  - Blood T lymphocyte subsets have been studied using monoclonal antibodies in 10
      chronic uremic patients treated with maintenance hemodialysis. Both total T
      lymphocytes identified by the antibody OKT3, and the helper-inducer T lymphocyte
      subset identified by the antibody OKT4 were found to be significantly lower than
      normal. The cytotoxic-suppressor T cell subset was only moderately, even if
      significantly reduced, so that the T4/T8 ratio in uremic patients was
      significantly lower than normal. These data provide an additional contribution to
      the interpretation of immunological and hematological deficiencies observed in
      chronic uremia.

PMID- 1369695
TI  - Can virostatic chemotherapy and/or adoptive allogeneic immunotherapy eradicate in
      vivo Friend's virus infection?
AB  - While none of the three drugs which exert an in vitro anti-HIV effect, neither
      AZT nor the other two, acriflavine and elliptinium, which we have shown to be
      more efficient than AZT, is able to eradicate Friend's virus in vivo, the
      combination of the 3 drugs at much smaller doses than when given alone seems able
      to eradicate it in almost 30% of the infected animals. This possible eradicating
      effect of virostatics in combination is compared with the results we had
      previously obtained with lymphocytes of virus-immunized allogeneic donors.

PMID- 1369696
TI  - World malaria situation in 1989.

PMID- 1369697
TI  - Malaria--Vancouver, British Columbia, 1991.

PMID- 1369699
TI  - Illness associated with seafood.

PMID- 1369698
TI  - Scombroid poisoning--an outbreak in two Ontario communities.

PMID- 1369700
TI  - Increasing resistance to antimicrobial agents among isolates of Neisseria
      gonorrhoeae in Ontario: trends 1989-1990.

PMID- 1369701
TI  - The role of calcium antagonists in the treatment of atherosclerosis and
      hypertension.
AB  - Results of animal studies suggest that calcium antagonists can inhibit the
      development of experimentally induced atherosclerosis. Although the biological
      process underlying this phenomenon has not been fully elucidated, several
      mechanisms have been proposed. Notably, calcium antagonists may suppress free
      radical-induced damage of the vascular endothelial cells with the consequent
      transport of low-density lipoproteins across the vascular endothelium and the
      accumulation of the lipids in the intima. Studies have shown that calcium
      antagonists can inhibit the stimulatory effects of epidermal growth factor on
      intracellular calcium concentrations and DNA synthesis in cultured rat aortic
      smooth muscle cells, but not those of platelet-derived growth factor or
      somatomedin C. Further experimental studies have demonstrated that calcium
      antagonists stimulate prostacyclin production and inhibit 12
      hydroxyeicosatetraenoic acid-induced vascular smooth muscle cell migration,
      therefore preventing platelet aggregation and intimal thickening, respectively.
      Despite the encouraging results in animals, comparatively few clinical studies
      have been undertaken to establish the efficacy of calcium antagonists in the
      prevention of cardiovascular disease in hypertensive patients. This, in part, is
      due to the technical difficulties associated with measuring coronary artery
      stenosis, but the recent development of a technique for the video-densitometric
      analysis of coronary angiograms has enabled stenotic regions to be quantified.
      Using this approach, a retrospective study has been undertaken of the efficacy of
      long-term treatment with a calcium antagonist on the progression of coronary
      atherosclerosis. Results are encouraging and a prospective long-term, multicenter
      trial is proposed.

PMID- 1369702
TI  - Clinical effects of calcium antagonists in hypertensive diabetics.
AB  - The incidence of hypertension and coronary artery disease among diabetic patients
      is approximately two to three times greater than in nondiabetics. Recent evidence
      suggests that even moderately elevated blood pressure levels may result in
      diabetic complications involving the eyes or kidneys. However, treatment of
      diabetic patients with antihypertensive drugs may have a deleterious metabolic
      effect. Previous studies have suggested that calcium antagonists may reduce
      insulin secretion and therefore impair glucose tolerance. This has not been
      substantiated clinically; in general, it would appear that calcium antagonists
      have a minimal hyperglycemic effect. To establish whether interruption of
      excitation-contraction coupling in arterial smooth muscle and altered stimulus
      secretion coupling occur at pharmacologically equivalent doses of calcium
      antagonist, the effect of nicardipine on insulin output and vascular resistance
      was studied in the isolated perfused rat pancreas and in eight hypertensive
      patients with impaired glucose tolerance during oral glucose tolerance testing
      (OGTT). Baseline insulin output in vitro was 86 +/- 22 ng/min at 8.0 mM glucose
      and 2.5 mM calcium. Application of 10 nM nicardipine reduced insulin output to
      86% of baseline, whereas output was reduced to 16% by 1 microM nicardipine and to
      6% by 10 mM nicardipine. Changes in duodenopancreatic outflow indicated maximal
      vasodilation of the pancreas at all three concentrations of nicardipine (10 nM-10
      mM). In vivo nicardipine 30 mg t.i.d. for 2 weeks reduced systolic blood pressure
      from 168 +/- 2 mm Hg to 136 +/- 4 mm Hg (p < 0.001) and diastolic blood pressure
      from 96 +/- 3 mm Hg to 78 +/- 2 mm Hg (p < 0.001).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1369703
TI  - The influence of nicardipine in patients with high risk of stroke.
AB  - Blood pressure and clinical status of 1,736 patients with cerebrovascular disease
      were observed during 12 months of treatment with nicardipine. The most common
      diagnoses were chronic cerebral ischemia (53.2%), transient ischemic attacks
      (TIA; 25.1%), and cerebral infarct (8.7%); 50.1% of patients were classed as
      hypertensive [systolic blood pressure (SBP) > or = 160 mm Hg or diastolic blood
      pressure (DBP) > or = 90 mm Hg]. Most patients (91.2%) received a daily dose of
      60 mg nicardipine. Additional treatments included diuretics (37%), beta-blockers
      (11.5%), other antihypertensive drugs (15.8%), platelet antiaggregants (25.1%),
      and cardiotonic drugs (15.1%). A total of 282 patients (16.2%) were lost to
      follow-up, 21 (1.2%) patients withdrew due to side effects, 32 (1.8%) died, and 9
      (0.5%) patients had treatment interrupted due to concomitant illness. In the
      hypertensive subgroup, blood pressure (SBP/DBP) was reduced from a mean baseline
      value of 175 +/- 22/97 +/- 14 mm Hg to 152 +/- 17/85 +/- 11 mm Hg at 3 months and
      149 +/- 23/81 +/- 11 mm Hg after 12 months of treatment. The incidence of TIA or
      stroke among these patients was reduced from 29 cases (3.5%) during the first 3
      months to 11 cases (1.54%) during months 4-12 (p < 0.01). In normotensive
      patients there were 18 (2.15%) cases during months 1-3 and 13 (1.55%) cases
      during months 4-12 (difference not significant). In the 280 patients treated with
      nicardipine alone, the most frequent side effects during the first month were
      facial flushing (6.8%), gastrointestinal problems (5%), dizziness (3.2%),
      headache (3.2%), drowsiness (3.2%), and hypotension (1.1%). Most of these side
      effects were transient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369704
TI  - The influence of nicardipine on left ventricular hemodynamics and compliance in
      patients with coronary heart disease.
AB  - The hemodynamic effects of nicardipine were studied in 10 normotensive patients
      (nine men, one woman; age 43-70 years, mean 56 years) and five patients with mild
      to moderate hypertension (four men, one woman; age 46-72 years, mean 62.8 years);
      in all patients coronary heart disease was confirmed by angiography. Hemodynamic
      parameters were determined before and after intravenous administration of
      nicardipine in cumulative doses of 2.5, 7.5, and 12.5 mg for 10 min each.
      Nicardipine significantly reduced systolic aortic pressure, diastolic aortic
      pressure, and mean aortic pressure in normotensive patients [139 +/- 8.7 vs. 114
      +/- 9.2 mm Hg (p < 0.001), 73 +/- 9.1 vs. 56 +/- 7.9 mm Hg (p < 0.001), 97 +/-
      7.8 vs. 7.8 +/- 7.9 mm Hg (p < 0.001), respectively] and in hypertensive patients
      [166 +/- 7.4 vs. 128 +/- 8.6 mm Hg (p < 0.001), 83 +/- 9.4 vs. 56 +/- 10.9 mm Hg
      (p < 0.001), 110 +/- 15.5 vs. 78 +/- 12.0 mm Hg (p < 0.001), respectively].
      Systemic vascular resistance was decreased significantly in hypertensive patients
      [1,363 +/- 188 vs. 707 +/- 137.7 dyn sec cm-5 (p < 0.001)] and in normotensive
      patients [1,110 +/- 225.3 vs. 682 +/- 92.4 dyn sec cm-5 (p < 0.001)]. Heart rate
      increased from 68 +/- 6.8 to 83 +/- 11.4 beats/min (p < 0.001) in normotensive
      patients but the increase from 72 +/- 14.7 to 80 +/- 14.2 beats/min in
      hypertensive patients was not significant. Mean pulmonary artery pressure did not
      change significantly in hypertensive patients and increased slightly in
      normotensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369705
TI  - The influence of nicardipine in type 2 diabetic patients with slight
      hypertension.
AB  - A double-blind, placebo-controlled study was carried out over 120 days to assess
      the metabolic tolerance and patient acceptability of nicardipine in 20 patients
      with Type 2 diabetes mellitus and slight hypertension. Following a 21-day washout
      period during which all patients received placebo, 13 men and 7 women (mean age
      45 years, systolic blood pressure 150-165 mm Hg or diastolic blood pressure 85
      100 mm Hg) were randomly assigned to treatment with oral nicardipine 60-90 mg/day
      (n = 9) or placebo (n = 11). No significant differences were observed between the
      nicardipine- and placebo-treated groups in terms of fasting and postprandial
      blood glucose concentrations, fasting plasma insulin levels, or glycosylated
      hemoglobin A1c after 60 and 120 days' treatment. There was also no change in the
      plasma levels of total cholesterol, HDL-cholesterol, triglycerides, and
      apolipoproteins. Side effects were minor and did not differ significantly between
      groups. All patients who had received nicardipine for 120 days wished to pursue
      treatment. Nicardipine, which was well tolerated, appears to be an interesting
      alternative for the treatment of mild essential hypertension in Type 2 diabetic
      patients, although further studies are required to establish its effects on renal
      function in this population.

PMID- 1369706
TI  - Calcium entry blockade and agonist-mediated vasoconstriction in hypertensive
      patients.
AB  - The effects of two chemically unrelated calcium channel blockers--nicardipine and
      verapamil--on vascular responses to exogenous norepinephrine were evaluated in
      uncomplicated hypertensive patients. Each drug was infused into the brachial
      artery at rates that did not affect systemic blood pressure or heart rate, and
      forearm blood flow was measured using strain gauge venous plethysmography.
      Nicardipine 1 microgram/100 ml forearm tissue/min dilated the forearm arterioles
      and antagonized the vasoconstrictor effect of norepinephrine, whereas verapamil 1
      microgram/100 ml tissue/min was ineffective, even though both drugs relaxed basal
      tone to the same extent. The difference between nicardipine and verapamil was
      also evident when reflex forearm vasoconstriction was elicited by the application
      of a lower body negative pressure and the drugs were infused intra-arterially at
      1 and 3 micrograms/100 ml tissue/min, respectively. To evaluate whether a
      comparable behavior might also hold for nonsympathomimetic agents, increasing
      doses of angiotensin II were administered to the forearm vascular bed after
      pretreatment with either nicardipine or verapamil. Both drugs increased forearm
      blood flow, but only nicardipine antagonized the effect of angiotensin II in the
      forearm, showing that the impairment of vasoconstrictor mechanisms was not
      dependent on a specific receptor. Important differences seem to exist between
      nicardipine and verapamil with regard to agonist-mediated vasoconstriction in
      hypertensive patients, which is consistent with the heterogeneity of calcium
      channel blockers as a pharmacological class. Preferential antagonism of a series
      of vasoconstrictor stimuli may characterize the vasodilatory and, possibly, the
      antihypertensive effect of nicardipine.

PMID- 1369707
TI  - The effects of nicardipine in elderly hypertensive patients.
AB  - Hypertension becomes more prevalent with advancing age, and the hemodynamic
      pattern differs from that in younger patients. In the elderly, elevated blood
      pressure is primarily due to reduced compliance of large vessels, resulting in an
      increase in total peripheral resistance, but in younger subjects it mainly
      reflects an increase in cardiac output. Vasodilator drugs, such as calcium
      antagonists, might therefore be expected to be particularly effective in lowering
      blood pressure in the elderly. Clinical experience has confirmed the safety and
      antihypertensive efficacy of these drugs, with some workers suggesting that
      calcium antagonists are particularly effective in the elderly. A 6-month
      multicenter study involving 2,184 patients has shown a direct correlation between
      pretreatment blood pressure and the degree of blood pressure reduction observed
      during nicardipine treatment with or without other antihypertensive drugs.
      Isolated systolic hypertension was significantly reduced but diastolic blood
      pressure was not affected. The incidence of side effects among elderly
      hypertensive patients, both with and without concomitant disease, was slightly
      lower than in younger patients.

PMID- 1369708
TI  - Clinical effects of calcium antagonists in silent ischemia.
AB  - A number of studies have addressed the response to calcium antagonists, used
      alone or combined with other therapy, in patients with silent myocardial ischemia
      (SMI). Nifedipine, the first calcium antagonist to be studied, was shown to be
      superior to pindolol in patients with effort angina. Although both nifedipine and
      diltiazem significantly reduced episodes of ST depression, compared with placebo,
      in patients with stable effort angina, the addition of nifedipine to diltiazem
      removed the beneficial effect of diltiazem in another study. Studies have shown a
      reduced incidence of ischemic episodes during nicardipine treatment in patients
      with ambulatory ischemia, predominantly SMI, and rest angina due to coronary
      artery spasm. Other workers similarly reported that verapamil was superior to
      both placebo and propranolol in reducing painful and painless ischemia in
      patients with angina at rest. It has been demonstrated that, compared with
      placebo, nifedipine reduced ischemic episodes by 50% and also markedly reduced
      total ischemic time in totally asymptomatic men with coronary artery disease and
      SMI. It was suggested that the well-documented increase in SMI occurring between
      0600 and 1200 h was reduced, but not eliminated, by nifedipine. Diltiazem may
      also attenuate the circadian variation in SMI. Nifedipine has been shown to be
      particularly effective in SMI when combined with a beta-blocker. This has been
      substantiated in a large group of patients; both drugs reduced the number of
      episodes of SMI when used as monotherapy, and the combination decreased the
      incidence by 95%. These findings collectively indicate that calcium antagonists
      are effective in reducing or preventing SMI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369709
TI  - Origin and metabolism of serotonin.
AB  - A brief review is given of the distribution of serotonin in tissues. The
      enzymatic steps in the biosynthesis and metabolism of serotonin are described,
      and factors involved in the regulation of the in vivo metabolism of serotonin are
      reviewed.

PMID- 1369710
TI  - Ischemia and Serotonin. Proceedings of a satellite symposium at the 15th World
      Congress of Angiology. Rome, Italy, September 17-22, 1989.

PMID- 1369711
TI  - Vascular effects of serotonin and ischemia.
AB  - Circulating 5-hydroxytryptamine originates in the gastrointestinal tract, where
      it overflows to the blood: part of that serotonin is taken up and stored by the
      platelets. When the latter aggregate, the released serotonin feeds back on the
      platelets to amplify the aggregation process; this amplification can be blocked
      with 5-HT2-serotonergic antagonists such as ketanserin and naftidrofuryl.
      Serotonin is taken up and destroyed by the endothelial cells; these cells also
      release endothelium-derived relaxing factor (EDRF) when exposed to the monoamine.
      The release of EDRF evoked by serotonin is not blocked by 5-HT2-serotonergic
      antagonists and involves a pertussis toxin-sensitive G-protein. When serotonin
      reaches vascular smooth muscle it usually causes it to contract; this, in most
      blood vessels, is prevented by 5-HT2-serotonergic antagonists. The contractions
      evoked by serotonin are reduced considerably in the presence of a normal
      endothelium. The same is true for contractions evoked by aggregating platelets,
      which release enough serotonin to activate receptors on both the endothelial
      cells (release of EDRF) and on vascular smooth muscle (contraction). Thus, 5-HT2
      serotonergic antagonists favor vasodilatation not only because they brake the
      amplifying effect that serotonin exerts on further platelet aggregation, but also
      because, by blocking the direct activation of the vascular smooth muscle by
      platelet-released serotonin, they facilitate the occurrence of endothelium
      dependent relaxations to the platelet products.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369712
TI  - Serotonin 5-HT2 receptors and brain circulation.
AB  - Most evidence in the literature concerning the role of serotonin in ischemia
      originates from brain research. This is partly because the central nervous system
      is particularly prone to accumulation of 5-HT, due to the neuronal sources of the
      amine in addition to circulating 5-HT from platelets. In ischemia, platelet
      invasion, rupture of the blood-brain barrier, liberation of 5-HT from nerve
      terminals inside the vessel wall, and necrosis of serotonergic neurons favor
      local increases of the transmitter in the brain. The pathophysiological
      consequences include amplifications of processes such as vasoconstriction of
      major and collateral arteries, edema formation, platelet aggregation, and blood
      sludging. 5-HT2 receptors appear to be the major effector of these actions of
      serotonin, judging from experimental and clinical pharmacology data with specific
      or partial 5-HT2 serotonergic antagonists. This review summarizes current
      knowledge on the key role serotonin plays in the induction or consequences of
      brain ischemia.

PMID- 1369713
TI  - Effects of naftidrofuryl on the contraction and proliferation of cultured
      myocytes evoked by serotonin.
AB  - We investigated the effects of 2-(diethylamino)-ethyl-tetrahydro-alpha-(l
      naphthylmethyl)-2-furanpro pionate (naftidrofuryl) on both the contraction and
      the proliferation of cultured rat aortic myocytes elicited by serotonin. Cells
      were cultured under controlled conditions, both on microcarrier beads and in
      microwells. The results show that naftidrofuryl alone had no effect on the
      properties of vascular smooth muscle cells. However, in the presence of
      serotonin, naftidrofuryl inhibits the contraction and the proliferation of smooth
      muscle cells.

PMID- 1369714
TI  - Influence of naftidrofuryl, a serotonergic antagonist, on erythrocyte
      aggregation.
AB  - Erythrocyte aggregation is an important determinant of the rheological behavior
      of blood and may play a critical role in nutritive tissue perfusion at the level
      of the microcirculation, particularly in situations of low flow. Thus, abnormal
      red blood cell aggregation may contribute to the pathophysiology of a variety of
      vascular diseases with associated microcirculatory disturbances. The action of
      serotonergic antagonists has a hemorheological component, although red blood cell
      aggregation specifically has not been addressed previously. Therefore, the effect
      of naftidrofuryl, a 5-hydroxytryptamine-2 receptor antagonist (5-HT2), on
      erythrocyte aggregation was studied in whole blood obtained from adult human
      volunteers. Red blood cell aggregation was measured using a Myrenne aggregometer
      the operation of which is based on nephelometric principles. The results
      demonstrate that red blood cell aggregation is significantly reduced in
      comparison to controls on incubation of whole blood in the presence of
      naftidrofuryl. This inhibitory effect is concentration dependent and reaches a
      maximum (approximately 30%) between 1 and 10 microM naftidrofuryl. Furthermore,
      naftidrofuryl (5 microM) also inhibits red blood cell aggregation in the presence
      of exogenously added serotonin (1 microM) on average by approximately 18%.
      Significant inhibition of red blood cell aggregation could not be observed in
      similar experiments using whole blood suspensions essentially devoid of
      platelets, suggesting that these blood cellular elements are involved in
      mediating the effects of naftidrofuryl.

PMID- 1369715
TI  - The effect of naftidrofuryl on red blood cell aggregation detected in vitro with
      ultrasound.
AB  - Red blood cell aggregates are mainly responsible for the echogenicity of flowing
      blood. Thus, ultrasound can be used to observe the degree of red blood cell
      aggregation in slow flow conditions. We quantified blood echogenicity to study
      aggregation tendency of red blood cells in blood of patients with claudication,
      patients with suspected venous thrombosis, and normal volunteers without and with
      in vitro addition of naftidrofuryl (10(-6) M). Normal volunteers showed lower
      original echogenicity than any group of patients, and claudication patients
      showed the highest echogenicity. Naftidrofuryl caused a fall in mean echogenicity
      in all groups, and its effect was pronounced on blood samples with a high
      original echogenicity.

PMID- 1369716
TI  - The effect of naftidrofuryl, a 5-HT2 antagonist, on collateral vascular responses
      to serotonin and to platelet activation.
AB  - Collateral arterial supersensitivity to serotonin has been attributed to a 5-HT2
      receptor mechanism because of the effectiveness of ketanserin in reversing that
      vasoconstrictor response. To assess that hypothesis we employed a chemically
      unrelated agent, naftidrofuryl, and assessed the responses of the collateral
      arterial supply 2 weeks after superficial femoral artery ligation to serotonin or
      to platelet activation induced by endothelial injury in 25 rabbits. Naftidrofuryl
      was effective in reversing serotonin-induced vasoconstriction in doses ranging
      from 0.3 to 3.0 micrograms/kg/min. Higher doses reduced blood pressure
      sufficiently that collateral arterial attenuation ensued. When collateral
      arterial vasoconstriction was induced by endothelial injury, naftidrofuryl in
      doses of 1.0 and 3.0 micrograms/kg/min reversed the attenuation (p < 0.001) in a
      dose-dependent fashion. In the absence of vasoconstriction induced by serotonin
      or platelet activation, naftidrofuryl in these doses did not produce
      vasodilatation, suggesting that the agent acted as a blocker rather than as a
      direct vasodilator. The observations strengthen the hypothesis that
      supersensitivity of collateral arterial vessels to serotonin reflects a 5-HT2
      receptor mechanism.

PMID- 1369717
TI  - Effect of serotonergic antagonism on local responses to an acute and selective
      endothelial trauma in vivo.
AB  - Serotonin is liberated during platelet release reaction. It is concluded from in
      vitro experiments that serotonin influences both platelet activation and thrombus
      induced vasoconstriction. The subject of the present study was to assess the
      impact of the serotonin2 antagonist naftidrofuryl on both thrombogenesis and
      thrombus-induced vasoconstriction in vivo. In a hamster cheek pouch, vessels form
      a rich meshwork, allowing repetitive experiments to obtain intraindividual
      control measurements. With a contactless photochemical process, endothelial cells
      can be damaged in vivo. Regularly platelets and the coagulation system are
      activated and thrombi are formed. In larger arterial vessels local
      vasoconstriction occurs. Thrombogenesis was induced in arterioles with an inner
      diameter between 17 and 20 microns. It was monitored by the continuous
      measurement of blood cell velocity to assess initial hemodynamics and the
      interval elapsing until perfusion stops. Solvent alone had no effect.
      Naftidrofuryl was given in clinically relevant dosages of 1, 5, and 20 mg/kg
      intra-arterially. Even 1 mg/kg showed a significant antithrombotic effect.
      Efficacy increased in a dose-related manner as well as during the time interval
      of observation (i.e., 2 h after application). As an established antithrombotic
      standard, acetylsalicylic acid was applied in dosages of 10 and 100 mg/kg. Both
      dosages were found to be antithrombotic, but not more effective than comparable
      dosages of naftidrofuryl. Larger arterioles with an inner diameter of about 50
      microns have smooth muscle cells. They constrict during thrombogenesis as a local
      response to substances released by the thrombus. Topical application of
      papaverine abolished vasoconstriction. A thromboxane antagonist (EP092) was also
      effective. Naftidrofuryl reduced the vasoconstriction whereas its solvent was
      without effect.

PMID- 1369718
TI  - Naftidrofuryl inhibits contractions to serotonin in intact and de-endothelialized
      cerebral arteries in vitro.
AB  - Excised segments of rabbit middle cerebral artery were cannulated and perfused in
      vitro at constant flow (1 ml/min). In vessels with intact endothelium, integrity
      of the intima was checked by determining relaxations to acetylcholine. In another
      series of segments, the endothelium was destroyed mechanically. Serotonin (5-HT)
      was added to the perfusate in increasing concentrations (3 x 10(-10) to 10(-4)
      M). Perfusion pressure served as the index of vasomotor responses of the arterial
      segment. At therapeutic concentrations, the 5-HT2 antagonist naftidrofuryl did
      not change perfusion pressure of normal vessels in the absence of 5-HT. Addition
      of 5-HT to intact vessels had no effect on perfusion pressure, but potentiated
      the contraction induced by KCl. This reaction was greatly amplified after de
      endothelialization. Addition of naftidrofuryl (10(-7) M) to the perfusate
      strongly inhibited 5-HT's contracting effects on both intact and
      deendothelialized arterial segments. Naftidrofuryl at 10(-6) M further displaced
      the dose-effect curve to the right in a competitive manner. These data confirm
      the potentiating effect of 5-HT on vascular smooth muscle (even in intact
      vessels) and the anticonstricting effects of naftidrofuryl when 5-HT2 receptors
      on smooth muscle cells are activated by serotonin.

PMID- 1369719
TI  - Role of serotonin in arteriolar thrombosis and secondary vasospasm.
AB  - Platelets are implicated both in the thrombotic reaction to an intimal lesion of
      the arteriolar wall and to the resulting vasospasm even if the two phenomena are
      not linked directly. The spastic reaction is a consequence of the thrombotic
      process because without localized platelet activation (thrombus formation) there
      is no vasospastic reaction, but by pharmacological manipulation, the thrombotic
      reaction can develop without resulting vasospasm. We developed an original
      experimental model that allowed us to study the thrombotic reaction secondary to
      localized endothelial injury in arterioles of the mesentery of the rat, as well
      as the vasospastic reaction downstream to the site of thrombus formation. In this
      setting, we studied the reactivity of Sprague-Dawley rats treated with three 5
      HT2 serotonergic antagonists (ketanserin, ritanserin, and naftidrofuryl) and that
      of Fawn-Hooded rats (a strain affected by a congenital reduction of platelet
      dense granules, with a resulting decrease in platelet content of serotonin, ADP,
      and catecholamines). Naftidrofuryl had antithrombotic properties similar to those
      of ritanserin but was less potent than ketanserin. It possessed antispastic
      activity against the reaction secondary to intravascular platelet activation. Its
      potency was similar to that of ketanserin but greater than that of ritanserin.
      Naftidrofuryl had no significant antispastic activity against platelet-derived
      agents reaching the ateriolar wall from the adventitial side. Compared to the
      Sprague-Dawley rat, Fawn-Hooded rats had a minimal reduction of the thrombotic
      process and of the intraluminal induced vasospasm but a similar response to
      adventitial stimulation of the arterial wall by vasoactive factors released from
      a neighboring hemostatic plug.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369721
TI  - Naftidrofuryl after acute stroke: a review and a hypothesis.
AB  - With demographic change, Western populations are becoming older. The prolonged
      decline in incidence of stroke, already a very costly illness, may soon reverse.
      This paper briefly reviews medical treatments of acute stroke that have been
      popular in the past and finds that they have been generally of little value. The
      place of naftidrofuryl, a drug with a complex pharmacological profile that
      includes selective S2-receptor blockade, is discussed in greater detail. Two
      clinical studies have indicated that, although it may not alter death rate in
      acute stroke, naftidrofuryl therapy enhances recovery from the disabling effects
      of cerebral infarction. One important consequence of this is a potentially major
      reduction in time spent in hospital by stroke patients. Hospital bed occupancy
      has been identified as a principal component in the cost of stroke to health
      services. Drug treatments that reduce death rate without improving recovery in
      survivors have an opposite effect, as has been seen in an important trial of
      glycerol.

PMID- 1369720
TI  - Chronic treatment with naftidrofuryl attenuates the development of vascular
      hypersensitivity to serotonin in the spontaneously hypertensive rat.
AB  - Three-month-old spontaneously hypertensive rats were treated for 1, 2, or 3
      months with daily intraperitoneal injections of naftidrofuryl (30 mg/kg).
      Systolic arterial pressure was measured. Tail arteries were removed and perfused
      at a constant flow rate of 2 ml/min. A concentration-response curve for serotonin
      was prepared. A second curve was then constructed in the presence of
      naftidrofuryl. Chronic treatment with naftidrofuryl had no effect on blood
      pressure but produced a decrease in the maximal vasoconstrictor response and the
      sensitivity to serotonin in vitro. The in vitro sensitivity to naftidrofuryl was
      unchanged. These studies suggest that chronic treatment with a dose of
      naftidrofuryl that does not modify blood pressure attenuates the in vitro
      vascular sensitivity to serotonin.

PMID- 1369722
TI  - Naftidrofuryl in the treatment of subacute stroke.
AB  - In a placebo-controlled, double-blind study, 82 patients in the subacute stage of
      a disabling stroke were studied to assess the effect on clinical improvement of
      600 mg naftidrofuryl against placebo. Forty-two patients were treated with the
      drug and 40 with placebo, in each case administered for 60 days. All patients
      received 100 mg aspirin and 300 mg dipyridamole daily and entered a similar
      program of rehabilitation therapy. At the start and the end of the study, the
      motor functions of the upper and lower limbs, the ability to walk and to perform
      daily activities, the comprehension and expression of speech, and the mental
      progress were assessed with quantitative linear scales. In the group treated with
      active drug, a greater overall tendency of improvement was observed, reaching
      statistically significant levels for walking and activities of daily life when
      compared to placebo-treated patients. Overall improvement was negatively
      influenced by advancing age, but the statistically significant effect of
      treatment on walking and daily activities was not interfered with by age. Right
      sided lesions showed better improvement under active drug than left-sided
      lesions. This may be due to a correctional effect of naftidrofuryl on hemispatial
      neglect.

PMID- 1369723
TI  - Indirect evaluation of blood oximetry by digitized conjunctival capillarography:
      effects of naftidrofuryl.
AB  - Microcirculatory disturbances are essential elements in peripheral and visceral
      oxygenation. Microcirculation can be studied by conjunctival angioscopy with
      morphological studies (arterioles, veinules, and capillaries appearances) and
      blood flow dynamics by digitized photographies (indirect oxymetric measurements
      in vivo). We studied the effects of naftidrofuryl on 20 atherosclerotic patients
      (mean 70 years old). After 3 months' treatment some parameters were significantly
      improved: interstitial edema, arteriolar sludge, and mainly vascular oxymetry.
      This means better microcirculatory hemodynamics and thus a better tissular
      oxygenation.

PMID- 1369724
TI  - Peripheral arterial occlusive disease: conservative treatment of intermittent
      claudication.
AB  - Intermittent claudication is the principal symptom in stage II of peripheral
      arterial occlusive disease. As this is a multilocular manifestation of
      atherosclerosis, a distinction must be drawn between treatment of the underlying
      disease with consideration of the individual risk factors and improvement and
      abolition of the intermittent claudication. Various therapeutic principles exist,
      and drug therapy is the subject of controversial discussion. On the basis of
      eight controlled, randomized studies, it was demonstrated that in comparison with
      placebo a statistically significant increase in the pain-free walking distance
      can be achieved by oral drug administration within 3-6 months. This drug therapy
      should be considered for those patients with intermittent claudication who cannot
      undergo revascularization, angioplasty, or walking training.

PMID- 1369726
TI  - Receptor "families" for 5-hydroxytryptamine.
AB  - Significant advances in the analysis of 5-hydroxytryptamine (5-HT) receptor
      subtypes occurred in the 1980s. Although the current status of 5-HT receptor
      pharmacology may appear confusing to many investigators, the evolving data
      suggest that 5-HT receptor subtypes can be categorized into three major
      "families." Each "family" consists of multiple receptor subtypes that share
      similarities in their molecular, biological, pharmacological, biochemical, and/or
      physiological properties. These receptor subtypes are present throughout the
      nervous system as well as in the periphery. A simple framework for the
      classification of 5-HT receptor subtypes is provided in the present review.

PMID- 1369725
TI  - Treatment of stage II chronic arterial disease of the lower limbs with the
      serotonergic antagonist naftidrofuryl: results after 6 months of a controlled,
      multicenter study.
AB  - A study was carried out in patients with intermittent claudication (Fontaine's
      stage II). The atheromatous origin of the disease was confirmed and localized by
      angiography or Doppler. One hundred eight-three patients were selected initially
      (day -30) with a pain-free walking distance on a treadmill (at a speed of 3 km/h
      and a slope of 10%) ranging from 150 to 300 m. During the first month (washout
      period) all patients received two placebo tablets daily. At the end of this run
      in period (day -30; day 0) and after checking walking distance stability (allowed
      variation: 20% between the two measurements), patients were included in the
      study. According to this criterion, 112 patients were selected and 94 remained
      during the whole study. The study was designed in double-blind, using two
      parallel, randomly selected groups. Fifty-two patients received naftidrofuryl (2
      x 316.5 mg tablets daily with meals) for 6 months; 42 patients received placebo
      under the same conditions. During this period, clinical and paraclinical
      examinations were carried out every quarter (day 90 and day 180). After checking
      the initial homogeneity of the naftidrofuryl and placebo groups, the comparison
      between the two groups indicates a significant improvement in the naftidrofuryl
      group after 3 months and 6 months of treatment, for the pain-free walking
      distance. For the maximal walking distance, a significant improvement was found
      at day 180. Nonparametric analysis (chi 2 test) also indicated a significant
      improvement for the naftidrofuryl group. These results confirm that naftidrofuryl
      is beneficial in the treatment of patients with chronic arterial disease.

PMID- 1369727
TI  - The effect of naftidrofuryl on intermittent claudication: a meta-analysis.
AB  - A meta-analysis was performed on four clinical trials, conducted during 1980-1989
      in France (two trials) and in the Federal Republic of Germany (two trials).
      Altogether, 596 patients with peripheral arterial occlusive disease (Fontaine's
      classification stage II) entered these four multicenter studies. Four hundred
      fifty-two patients completed the trials, 241 were treated with 600 mg
      naftidrofuryl orally per day and 211 were given a placebo. The studies were of a
      double-blind parallel design and lasted for 3 or 6 months. Inclusion and
      exclusion criteria were comparable, as were the experimental methods used.
      Occasionally, differences in study design and methods were observed. Risk factors
      were recorded in three of the four studies. The outcome criterion of pain-free
      walking distance was studied for the four trials together and showed a
      significant improvement in the active drug tested group, following both 3- and 6
      month duration of treatment. The type of treatment, the severity of the disease,
      the existence of blood lipid disorders, and smoking were found to be the
      predictive factors associated with the evolution of pain-free walking distance
      during 3 months. The meta-analysis confirms the beneficial effect of
      naftidrofuryl in treating peripheral arterial occlusive disease.

PMID- 1369728
TI  - Mutants shed light on plant development.

PMID- 1369729
TI  - Cloning high molecular weight DNA fragments by the bacteriophage P1 system.
AB  - The cloning of high molecular weight genomic DNA promises to provide the means of
      mapping chromosomes, isolating genes, and understanding long-range effects on
      gene expression. This review describes the background and some recent advances in
      cloning of high molecular weight DNA using the bacteriophage P1 system.

PMID- 1369730
TI  - Wilms' tumour: reconciling genetics and biology.
AB  - Wilms' tumour, a paediatric malignancy of the kidney, is a striking example of
      the relationship between aberrant development and cancer. Several different
      genetic loci have been implicated in the aetiology of the tumour; genomic
      imprinting also plays a role. One Wilms' tumour predisposition gene (WT1),
      encoding a zinc finger protein, is expressed in a limited set of tissues,
      including developing nephrons and gonads. The biology and genetics of Wilms'
      tumour underline the developmental relationship between kidneys and gonads.

PMID- 1369731
TI  - Plant transcription factors: present knowledge and future challenges.
AB  - By the use of three different experimental approaches, more than 40 cDNA clones
      encoding putative transcription factors have been isolated from plants. In this
      review, we compare the relative advantages and disadvantages of each approach,
      suggest methods for investigating the activity of the factors in vitro and in
      vivo, and discuss strategies to elucidate their physiological functions during
      plant growth and development.

PMID- 1369733
TI  - Barley genetics--not only here for the beer.

PMID- 1369732
TI  - Conservation and evolution of transcriptional mechanisms in eukaryotes.
AB  - Eukaryotic transcriptional activators play key roles in controlling cell growth
      and specifying embryonic development. These activators can stimulate promoters
      from distances up to tens of kilobases by a mechanism that is remarkably
      conserved in eukaryotes ranging from yeast to humans. Although the primary
      sequence of certain activators has also been conserved in widely divergent
      organisms, the regulatory roles that these factors play have been altered over
      evolution to fit the specific needs of the host.

PMID- 1369734
TI  - Mitotic gold in a mold: Aspergillus genetics and the biology of mitosis.
AB  - The analysis of fungal mutants has had an extraordinary impact on our
      understanding of the biochemistry and regulation of mitosis. In this article we
      review the contribution of work on the filamentous fungus Aspergillus nidulans to
      the molecular genetics of mitosis.

PMID- 1369735
TI  - A rapid and efficient method for freezing and recovering clones of embryonic stem
      cells.

PMID- 1369736
TI  - Preparation of radiolabelled hybridization probes by STS labelling.

PMID- 1369737
TI  - Safe disposal of diaminobenzidine.

PMID- 1369738
TI  - Insistent and intransigent: a phage Mu enhancer functions in trans.

PMID- 1369740
TI  - Mesoderm induction and development of the embryonic axis in amniotes.
AB  - The mechanisms controlling the formation of the embryonic axis, and specifically
      those that give rise to the mesoderm, have received renewed attention recently.
      In the frog, some of these mechanisms have begun to be elucidated, and several
      factors have been found to cause uncommitted ectoderm cells to differentiate into
      mesoderm. All of the factors identified to date are related either to fibroblast
      growth factor (FGF) or to transforming growth factor beta (TGF-beta). Do the
      mechanisms that generate the embryonic axis of amphibians also operate in chick
      and mouse embryos? Here I address how amphibian and amniote embryos might provide
      complementary pieces of a puzzle.

PMID- 1369739
TI  - Homeodomains and regulation of sexual development in basidiomycetes.

PMID- 1369741
TI  - Molecular genetics of sex determination in C. elegans.
AB  - Sexual fate in the nematode Caenorhabditis elegans is controlled by a group of
      genetically well-characterized genes. Several of these sex-determining genes have
      now been analysed at the molecular level. Transcriptional regulation is likely to
      control both commitment to a single sexual fate and maintenance of that decision;
      in addition, intercellular signalling appears to coordinate the sexual fates of
      cells throughout the animal to adopt a single sexual fate.

PMID- 1369742
TI  - X-chromosome inactivation and cell memory.
AB  - Mammalian X-chromosome inactivation is an excellent example of the faithful
      maintenance of a determined chromosomal state. As such, it may provide insight
      into the mechanisms for cell memory, defined as the faithful maintenance of a
      determined state in clonally derived progeny cells. We review here the aspects of
      X-chromosome inactivation that are relevant to cell memory and discuss the
      various molecular mechanisms that have been proposed to explain its occurrence,
      with emphasis on DNA methylation and a recently proposed mechanism that depends
      on the timing of replication.

PMID- 1369743
TI  - Ustilago maydis, the delightful blight.
AB  - Recent studies of the corn smut fungus life cycle and its regulation by two
      mating type loci and other genes provide a cornucopia of challenges in cell
      biology, genetics and protein structure. The fungus can exist in two states:
      nonpathogenic and pathogenic. The change from one state to the other is
      accompanied by a change in morphology (yeast-like to filamentous) and growth
      properties (saprophytic to parasitic).

PMID- 1369744
TI  - The retinoblastoma protein and cell cycle regulation.
AB  - Although the precise function of the retinoblastoma gene product, p110RB1,
      remains unknown, recent data suggest that it plays a role in the control of
      cellular proliferation by regulating transcription of genes required for a cell
      to enter or stay in a quiescent or G0 state, or for progression through the G1
      phase of the cell cycle. However, it is difficult to rationalize the expression
      of p110RB1 in a wide range of tissues with the fact that mutations in the RB1
      gene initiate cancers in a limited number of tissues.

PMID- 1369745
TI  - [The external radiotherapy of differentiated thyroid carcinoma].

PMID- 1369746
TI  - [Combination of interferon-alpha with cytostatic drugs: a potentially successful
      therapeutic approach in metastatic melanoma].
AB  - Pharmacological treatment of disseminated melanoma is characterized by rather low
      objective response rates with mono- and combined chemotherapy and by significant
      toxicity. For these reasons, many centres do not now offer any systemic treatment
      to melanoma patients with distant metastases. Systemic treatment with interferons
      has not fulfilled all that was expected of it, but type-I interferons (-alpha, 
      beta) have proved to be effective in about 10-15% of patients treated. The
      antitumour activity of these substances seems to be related mainly to their
      antiproliferative effect, whereas no immunomodulatory effects have been
      substantiated in clinical trials. Combined therapy with interferons and
      cytostatic drugs was introduced into clinical trials only a few years ago, and
      the initial results are promising. Large studies with a total of over 200
      patients have already been performed to evaluate the combination of interferon
      alpha and dacarbazine. This treatment was effective in around 50% of the
      patients, complete or partial remission being achieved in 30% and stabilization
      of the disease, in 20%. Toxicity is significant, but still manageable; the new
      generation of antiemetic drugs (serotonin receptor blockers), in particular
      appears promising. Up to now, no improvement of efficacy has been found following
      addition of interferon-alpha to cisplatin in four clinical trials. In a study in
      our own department, however, the combined action of interferon alpha and
      vindesine was found to be superior to that of either used as a single agent, and
      the combination was well tolerated on an outpatient basis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1369747
TI  - [Low risk of cancer after treatment of hyperthyroidism with iodine-131].

PMID- 1369748
TI  - [A fatal course of combined acute appendicitis and mononucleosis infection].

PMID- 1369749
TI  - [Differences in risk factors for disease and in health problems between monks and
      the general population in The Netherlands].

PMID- 1369750
TI  - [Hobby horse rider against psychoanalysis. Concluding comments on a contribution
      by Walter Brautigam].

PMID- 1369751
TI  - [Patient information prior to sterilization].
AB  - The law in Denmark prescribes that the patient and the general practitioner to
      whom the patient directs his or her request for sterilization are obliged to
      confirm by their signatures that the patient has received information about
      sterilization, its risk and consequences. We asked 97 men and 96 women, if they
      had received this information prior to their sterilization. They were also asked
      about their knowledge about sterilization. 54% of the women and 35% of the men
      indicated that they had not received information. Only few of these wished
      further information by the hospital doctor. Knowledge about sterilization was
      good. It is concluded that the information to the patient prior to sterilization
      is far from optimal. The patients' signature confirming verbal information is not
      a sufficient safeguard. We recommend, among other things, that the patient should
      receive written information and that both the general practitioner and the
      hospital responsible for the operation should ensure that optimal information is
      received by the patient.

PMID- 1369753
TI  - [Comments on the paper by Th. Bein et al. Rupture of the trachea in difficult
      intubation, and on the paper by D. Jooss et al. Bronchial rupture].

PMID- 1369752
TI  - [Comment on the case report "Hygroma colli--sonographic indications of fetal
      chromosome abnormality", by A. Yilmazturk and F. Deppermann].

PMID- 1369754
TI  - [Reproductive and developmental toxicity study of 6-amidino-2-naphthyl 4(-)[(4,5
      dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187). (II)-
      Oral administration to rats during the period of fetal organogenesis (prenatal
      examination)
AB  - 6-Amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate
      dimethanesulfonate (FUT-187) was given orally to pregnant Crj : CD (Sprague
      Dawley) rats from days 7 through 17 of gestation at dose levels of 50, 200 and
      800 mg/kg/day. In the 800 mg/kg/day group, salivation just after dosing,
      suppression in body weight gain and decreased food consumption were observed. No
      external, visceral and skeletal anomalies attributable to FUT-187 were observed
      in fetuses. From the present result, it is considered that the no-effect dose
      level of FUT-187 for dams and fetuses are 200 mg/kg/day and 800 mg/kg/day
      respectively.

PMID- 1369755
TI  - [Reproductive and developmental toxicity studies of 6-amidino-2-naphthyl 4(
      )[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187).
      (IV)--Oral administration to New Zealand white rabbits during the period of fetal
      organogenesis.
AB  - Oral administration of 6-amidino-2-naphthyl 4(-)[(4,5-dihydro-1H-imidazol-2
      yl)amino] benzoate dimethanesulfonate (FUT-187) at doses of 10, 30 and 100 mg/kg
      was given to New Zealand White rabbits on days 6 to 18 of gestation. The
      following results were obtained. Decreased food consumption and suppression of
      body weight gain in dams were observed and these changes contributed to the
      increase in aborted or prematured births and increased fetal mortality at the 100
      mg/kg group. There were changes attributable to FUT-187 on external, skeletal and
      visceral examinations of fetuses. Based on the above, the no-effect dose level in
      dams and fetuses in the present study is 30 mg/kg/day.

PMID- 1369756
TI  - Survival in chronic granulocytic leukemia.

PMID- 1369757
TI  - Biophysical principles of sensory transduction.

PMID- 1369758
TI  - Visual pigments and inherited variation in human vision.

PMID- 1369759
TI  - Cyclic nucleotide-gated channels of vertebrate photoreceptor cells and olfactory
      epithelium.

PMID- 1369760
TI  - Transduction in retinal photoreceptor cells.

PMID- 1369761
TI  - Mechanisms of amplification, deactivation, and noise reduction in invertebrate
      photoreceptors.
AB  - In this review we have discussed the problem of deactivation at both the
      rhodopsin and G protein levels. Of particular interest is the novel observation
      that rhodopsin deactivation can be modulated by light. This modulation is likely
      to play an important role in light adaptation by reducing the gain of
      transduction. One interesting possibility is that this modulation involves the
      phosphorylation of an arrestin-like molecule, but this remains to be tested. One
      of the experimental advantages of Limulus photoreceptors is the large size of the
      single photon responses and the fact that even single G proteins produce a
      detectable response. This made possible the observation that nonhydrolyzable GTP
      analogues produce discrete transient events rather than the step-like events that
      would be predicted by previous models. This observation led us to a new view of
      how enzyme deactivation is coupled to GTP hydrolysis on G protein. According to
      this view, enzymes are activated by G protein, but can be deactivated by
      processes that are not dependent on G protein or the hydrolysis of GTP. We have
      conducted several types of experiments, including some on the vertebrate rod
      system, that strongly support this hypothesis. A second major theme of this
      review is transduction noise. The available biochemical evidence suggests that
      both G protein and G protein-activated enzymes are likely to become spontaneously
      active and generate undesirable noise. Our measurements indicate, however, that
      this noise is orders of magnitude smaller than would be predicted by simple
      models, suggesting that special mechanisms must exist for suppressing this noise.
      We have proposed a specific mechanism by which enzymes regulated allosterically
      by multiple subunits could act as coincidence detectors to reduce transduction
      noise. Finally, there is the fundamental question of which second messengers have
      a direct role in invertebrate phototransduction. After Fesenko et al. (1985)
      showed that the light-dependent conductance in vertebrate rods was modulated by
      cGMP and not by Ca2+, there was rapid progress in understanding the vertebrate
      photoreceptor transduction mechanism. Now that it has been established that
      invertebrate light-dependent channels are regulated by cGMP and not by Ca2+, we
      can expect rapid progress in understanding invertebrate phototransduction. A key
      question that needs to be answered is whether the InsP3-Ca2+ pathway somehow
      triggers changes in cGMP or whether there is an altogether different pathway by
      which cGMP metabolizing enzymes are affected by light.

PMID- 1369762
TI  - Toward a consensus working model for olfactory transduction.

PMID- 1369763
TI  - The inositol-lipid pathway is necessary for light excitation in fly
      photoreceptors.

PMID- 1369764
TI  - Response of Escherichia coli to novel gradients.

PMID- 1369766
TI  - Role of K+ channels in taste transduction.

PMID- 1369765
TI  - Discrimination of low-frequency magnetic fields by honeybees: biophysics and
      experimental tests.

PMID- 1369767
TI  - Role of amiloride-sensitive sodium channels in taste.

PMID- 1369768
TI  - Peripheral events in taste transduction.

PMID- 1369769
TI  - Transduction and adaptation in vertebrate hair cells: correlating structure with
      function.

PMID- 1369770
TI  - Hair-bundle mechanics and a model for mechanoelectrical transduction by hair
      cells.

PMID- 1369771
TI  - Cochlear hair cell function reflected in intracellular recordings in vivo.

PMID- 1369772
TI  - A novel multigene family may encode odorant receptors.

PMID- 1369773
TI  - Mammalian hearing and the cellular mechanisms of the cochlear amplifier.

PMID- 1369775
TI  - Physiology of transduction in the single olfactory sensory neuron.

PMID- 1369774
TI  - The molecular basis of signal transduction in olfactory sensory neurons.
AB  - Contributions from a wide spectrum of experimental systems have resulted in a
      dramatic increase in our understanding of this old and most enigmatic of the
      sensory systems. Many of the components of the odorant-induced transduction
      cascade have now been cloned, and the biochemistry, pharmacology, and regulatory
      mechanisms are being addressed in a logical fashion. One of the first priorities
      is to establish that the large family of putative receptor proteins described by
      Buck and Axel (1991) do, in fact, bind odorants. The ability to express members
      of this receptor family at high levels in the mammalian expression system is a
      first step in this direction. Determining specific ligand-receptor relationships
      is an extremely challenging task given the diversity of odorants able to be
      perceived and the potentially large size of the family of receptors. The role of
      other proteins in odorant presentation and processing, such as odorant binding
      protein produced in the lateral nasal gland (Pevsner et al., 1988), can be
      explored. A fascinating issue to be resolved is that of the distribution of
      receptor molecules within the population of olfactory sensory neurons. Does one
      cell express only one receptor, a small repertoire of receptors, or indeed the
      entire family? These questions can now be answered using a combined approach with
      in situ hybridization, immunocytochemistry, and single cell PCR techniques. One
      model of receptor distribution would provide for discrimination of a particular
      odorant by higher order analysis of the pattern of receptor neuron firing within
      the neuroepithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369776
TI  - Olfactory reception: from transduction to human genetics.

PMID- 1369777
TI  - Molecular mechanisms of olfactory signal transduction.

PMID- 1369778
TI  - [Focal nodular hyperplasia of the liver].
AB  - For several weeks a 27-year-old man had experienced a pressure sensation and
      noticed a spherical area of resistance in the epigastrium. On physical
      examination the firm, elastic tumour seemed most likely to be arising from the
      liver. Sonography recorded a 7.4 x 10.5 cm echo-poor structure. Computed
      tomography demonstrated in the tumour a central star-like, hypodense zone which
      filled with contrast medium, a finding typical of focal nodular hyperplasia.
      Functional hepatobiliary scintigraphy and histological examination of a fine
      needle biopsy from the tumour (slightly enlarged hepatocytes, portal reticular
      fibrosis, ductular proliferation) confirmed the diagnosis. As there was no danger
      of rupture and no sign of local compression surgical intervention was not
      indicated, but regular ultrasound monitoring is planned.

PMID- 1369779
TI  - [Mother knows best; the diagnosis of prelingual deafness].

PMID- 1369780
TI  - [Long-term therapy after an acute myocardial infarct].

PMID- 1369781
TI  - [Hemoglobinopathies, screening and molecular-genetic studies in foreign women in
      The Netherlands].

PMID- 1369782
TI  - [Chest pain caused by sumatriptan].

PMID- 1369783
TI  - [Demand and supply of internists in The Netherlands].

PMID- 1369784
TI  - [Invagination: the importance of early diagnosis].

PMID- 1369785
TI  - [Comments on Gubler Gh. Luthy R. M.: "Fever of unknown origin in general
      practice: what to do?"].

PMID- 1369786
TI  - [Did decubitus research remain stationary?].

PMID- 1369787
TI  - [The cost of arterial hypertension in Spain].
AB  - BACKGROUND: High blood pressure has a high incidence and produces a high
      morbidity and mortality due to associated diseases: cerebrovascular disease,
      ischemic cardiopathy, and cardiac failure. The socioeconomic impact of high blood
      pressure in Spain was estimated during 1985 in primary, hospitalary and
      pharmaceutical health care, to provide a framework for decision making and to
      determine strategies for reducing the costs of this entity. METHODS: The
      methodology of analysis of the cost of the disease was followed with the aim of
      quantifying the socioeconomic consequences of an entity, disease or risk factor
      with prevalence being the focus of the study. RESULTS: The socioeconomic impact
      estimated was situated between 95,000 and 124,000 millions of pesetas according
      to the different hypothesis adopted in the analysis of sensitivity. The direct
      health care costs represented between 2.6 and 3.9% of the global health care
      costs for Spain in 1985. Health care funding consumed by high blood pressure in
      primary health care was higher (between 4.5 and 6.7%) than hospital attendance
      (between 1.0 and 1.5%) and pharmaceutical care (between 2.3 and 3.5%), with
      respect to the total costs of each category. CONCLUSIONS: The reduction of the
      costs related with high blood pressure in Spain must be obtained from improvement
      of efficacy of interventions carried out in health care education and primary
      health care. The economic evaluation of the primary and secondary prevention
      programs may aid in determining more cost-effective strategies.

PMID- 1369788
TI  - [8th Meeting of the Yugoslavian Plastic and Maxillofacial Surgery Association.
      Zagreb, May 30-June 1, 1990. Abstract].

PMID- 1369789
TI  - Life-style, health, and politically correct science.

PMID- 1369790
TI  - Health effects of smoking: current concepts.

PMID- 1369791
TI  - Maudie: the life and times of McGill's Maude Abbott.
AB  - This article is an account of the life of Dr. Maude Abbott, the turn-of-the
      century Canadian pioneer physician who founded what is now the International
      Academy of Pathology. She developed a system for the classification of medical
      museum specimens, accumulated the world's largest collection of congenital heart
      disease cases, and published historical works outside the field of medicine. A
      protegee and friend of Sir William Osler, she was guided by his counsel and
      inspired by his example. With Osler and Banting, she was one of the giants of
      Canadian medicine in the first half of the 20th century.

PMID- 1369792
TI  - Aneuploidy in nonneoplastic and benign melanocytic and breast lesions determined
      by DNA flow cytometry.
AB  - A total of ten of 60 nonneoplastic lesions and eight of 76 benign neoplasms of
      skin and breast showed an aneuploid peak in DNA flow cytometry profiles obtained
      from archival paraffin blocks. This confirms previous similar scattered reports
      and emphasizes that caution needs to be exercised in interpreting aneuploidy in
      DNA flow cytometry to mean preneoplasia, neoplasia, or malignancy.

PMID- 1369793
TI  - Subcellular localization of HMFG2 in breast carcinomas: an immunohistochemical
      and immunoelectron microscopic study.
AB  - Malignant transformation of human cells is associated with morphological and
      biochemical alterations. We have studied the distribution and pattern of staining
      of HMFG2 (human milk fat globulin) in normal breast, benign breast lesions, and
      137 primary and metastatic breast carcinomas. Immunohistochemical staining was
      performed with an antibody to HMFG2 using the indirect peroxidase technique.
      Three patterns of staining were noted: 1) secretion and luminal staining (in
      normal breast, most benign breast lesions and some breast carcinomas); 2) plasma
      membrane staining (in breast carcinomas); 3) intracytoplasmic staining (in breast
      carcinomas). Immunoelectron microscopy was also performed on normal breast,
      infiltrating duct, and lobular carcinomas. Immunoelectron microscopy showed
      localization of the gold particles on the electron dense granules of the HMFG2
      protein. These were localized along the surface of the extracytoplasmic lumina in
      normal breast ducts/acini and breast carcinomas, whereas localization was also
      noted within the intracytoplasmic lumina in cancer cells only. These results show
      that there is altered localization of milk fat globulin in breast cancer cells
      associated with membrane internalization and formation of intracytoplasmic
      lumina. This contributes to the understanding of the phenotypic alterations
      associated with malignant transformation in breast cancer.

PMID- 1369794
TI  - Appendiceal involvement in ulcerative colitis.
AB  - Little information has been published regarding appendiceal changes in ulcerative
      colitis of any extent. An early study has shown the appendix to be involved in
      over 50% of all cases of ulcerative colitis for which a proctocolectomy was
      performed, but the extent of the colitis was not always defined. While some
      investigators have found appendiceal involvement only in continuity with adjacent
      involved cecum, others believed it may occur as a skip lesion. In this study, the
      colons and nonobliterated appendices of 87 patients who underwent total
      proctocolectomy for ulcerative pancolitis were examined to determine the
      frequency of appendiceal involvement and to determine the frequency with which
      such involvement truly occurs as a skip lesion. All 87 cases had ulcerative
      pancolitis, and 66 (62%) had colitic changes in the appendix. In the remaining 21
      cases, there was no appendiceal inflammation. In all cases in which the appendix
      was involved, the cecum was also involved. Cecal activity or lack of activity
      correlated with appendiceal activity in 52 of the 87 cases (60%). Of the 35 cases
      in which there was some discrepancy in disease activity between the appendix and
      cecum, nine had more active disease in the appendix, and 26 had greater activity
      in the cecum, but in none of the cases where the cecum was normal or near normal
      was the appendix more severely involved. These data suggest that appendiceal
      involvement in resected ulcerative pancolitis always occurs in continuity with
      adjacent involved cecum, although there may be differences in disease activity
      between the two sites.

PMID- 1369795
TI  - Histologic changes in liver allograft biopsies associated with elevated whole
      blood and tissue cyclosporine concentrations.
AB  - Cyclosporine is used in the postoperative management of rejection in liver
      allograft recipients. Despite its efficacy in the treatment of allograft
      rejection, the drug exhibits toxicity at elevated whole blood concentrations
      including nephrotoxicity with associated histologic changes, and evidence of
      hepatotoxicity as determined by liver function studies. To date, there have been
      few published reports describing histologic changes in liver biopsies from
      patients with elevated blood cyclosporine levels. In the present study, we
      retrospectively examined biopsies from 16 liver allograft recipients, seven
      patients with elevated whole blood cyclosporine levels (> 1000 ng/ml) and nine
      control patients who had whole blood cyclosporine levels in the therapeutic range
      (558 to 993 ng/ml). In each case, frozen liver biopsy tissue was available to
      measure tissue levels of cyclosporine and metabolites. The blood and tissue drug
      levels were then correlated with the histologic changes present in the biopsy
      specimens. Patients with increased cyclosporine levels displayed histologic
      changes consisting of hypertrophy of the bile ductal epithelium with cytoplasmic
      vacuoles and the presence of "foamy" material within the hepatic sinusoids that
      were either absent or occurred less frequently in the control group. The
      histologic changes correlated best with cyclosporine metabolite levels rather
      than tissue levels of native drug. When liver function studies were correlated
      with cyclosporine levels, only gamma glutamyl transpeptidase (GGT) demonstrated a
      significant positive correlation with the histologic changes.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1369796
TI  - Nephrogenic adenomas of the urethra involving the prostate gland: a report of two
      cases of a lesion that may be confused with prostatic adenocarcinoma.
AB  - Two cases of urethral nephrogenic adenoma involving the prostate are described. A
      diagnosis of prostatic carcinoma was raised in both cases and was seriously
      entertained in one of them. The patients, who were 65 and 68 yr old, underwent
      transurethral resection because of difficulty voiding; both had had a prior
      similar procedure. Microscopic examination in each case showed small tubules and
      clusters of cells in the fibromuscular stroma of the prostate. In one case the
      lesional cells had abundant clear cytoplasm, and in both cases some of the nuclei
      had prominent nucleoli. In each case a minor component of the cystic pattern of
      nephrogenic adenoma was also present. Features pointing to a diagnosis of
      nephrogenic adenoma were a morphology that was diagnosis of nephrogenic adenoma
      were a morphology that was focally characteristic of that lesion, an origin from
      overlying prostatic urethra in both cases, and negative immunohistochemical
      staining of the lesional cells for prostate-specific antigen and prostate
      specific acid phosphatase. These cases illustrate that nephrogenic adenoma
      occasionally involves the prostate and in these cases can potentially be confused
      with prostatic adenocarcinoma.

PMID- 1369797
TI  - Immunocytochemical characterization of male breast cancer.
AB  - Biologic properties of breast cancer in men that might reflect alterations in
      pathogenesis from the disease in women were examined. We studied 22 tumors from
      males, 18 invasive carcinomas, three of which were papillary, and three in situ
      tumors of which one was papillary, and one papilloma. Our data support the
      previously reported high incidence of papillary carcinoma in men. Estrogen
      receptor status and the expression of cancer-associated antigens recognized by
      antibodies DF3, B73.2, SP-1, and c-erbB-2 were compared to matched tumors from
      females. Immunocytochemistry was performed on formalin-fixed, paraffin-embedded
      sections using standard avidin-biotin techniques; anti-PSA was used to exclude
      the possibility of metatastic prostate cancer, and 12 cases of gynecomastia were
      included as nonmalignant controls. The incidence of estrogen receptor positivity
      was higher in tumors from males (73%) than from females (54%), as has been
      reported previously. The range of expression of all breast cancer antigens tested
      in male tumors was similar to that observed in females, but some interesting
      differences were noted. With the exception of the anti-mucin DF3, all the
      antibodies reacted only with neoplastic tissues. Expression of the oncoprotein c
      erbB-2 was lower (17%) in males than in females (33%), despite the preponderance
      in men of the large-cell type carcinomas that have been associated with c-erbB-2
      expression. Unexpectedly, the pregnancy-associated hormone detected by SP-1 was
      expressed in 33% of tumors from males and, in contrast to females, was found in
      less differentiated tumors.

PMID- 1369798
TI  - DNA ploidy analysis of pleural mesotheliomas: its usefulness for their
      distinction from lung adenocarcinomas.
AB  - The distinction of malignant mesotheliomas from adenocarcinomas with pleural
      involvement is often difficult, even with electron microscopic and state-of-the
      art histochemical and immunologic studies. We evaluated the DNA ploidy and cell
      cycle of 45 clinically, morphologically, and immunohistochemically well
      characterized malignant mesotheliomas to establish their ploidy profile and
      compared it with that of 41 pulmonary adenocarcinomas. All the cases were mucin
      negative and had been immunophenotyped with the following monoclonal antibodies:
      anti-keratin, anti-CEA, anti-Vimentin, anti-HMFG2, Leu M1 (CD15) and B72.3.
      Single cell suspensions from the paraffin blocks were prepared following Hedley's
      technique and were analyzed with a Coulter EPICS V flow cytometer. The resulting
      histograms were interpreted with the Multicycle software program. Five cases were
      excluded due to their high coefficients of variation. DNA aneuploidy was defined
      by the presence of more than one G0/G1 peak on the histograms obtained
      exclusively from the tumor sample. With this criterion, there is a possibility of
      missing aneuploid cases with a single aneuploid cycling population; however,
      fixatives and time of fixation produce such a remarkable variation in the
      fluorochrome uptake that any control, other than normal tissue present in the
      sample, was rendered unreliable. Five (14%) cases were DNA aneuploid with DNA
      indexes ranging from 1.2 to 1.9 (mean = 1.5). Three cases had increased S + G2/M
      values. Of the aneuploid cases, four were epithelial and one sarcomatous. In
      comparison, aneuploidy was found in 31 (75%) of the lung adenocarcinomas studied
      (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1369799
TI  - Mucinous (so-called colloid) carcinomas of lung.
AB  - We present 24 cases of primary mucinous (so-called colloid) carcinomas of the
      lung. The patients were between 33 and 81 yr old (median: 57 yr), including 15
      men and nine women. The lesions were discovered incidentally on chest X-ray,
      where they presented in diverse forms. No predilection for a particular lobe or
      pulmonary segment was observed. The tumors varied from 0.5 to 10 cm in greatest
      diameter. Grossly, the tumors were poorly circumscribed, soft, tan-to-gray mucoid
      lesions. Microscopically, they showed intra-alveolar pools of mucin containing
      small clusters of atypical cells floating in the mucin, and foci of neoplastic
      columnar epithelium lining scattered alveoli. Seven cases showed areas of solid,
      well-differentiated malignant glands adjacent to pools of mucin. In two cases,
      lymph node metastases were found at surgery. Eleven (57%) of 19 patients were
      alive over a follow-up period ranging from 2 to 192 mo; one of them had
      metastases to bone and another had intrapulmonary recurrence. Eight patients died
      with/of their tumors, two of them with known metastases to bone and/or brain, and
      one with recurrence after 2 yr of initial diagnosis. No follow-up was obtained in
      five patients. Although the extent of clinical evaluation varied, no other
      primary neoplasms (i.e., breast, gastrointestinal tract, or other organs where
      primary mucinous carcinomas are known to occur) were observed. These tumors
      probably represent a variant of bronchioloalveolar carcinoma and share the
      prognosis of that neoplasm. However, because of their often bland cytologic
      features and paucity of malignant cells, they may be difficult to diagnose as
      neoplasms.

PMID- 1369800
TI  - Giant cell fibroblastoma in childhood immunohistochemical and ultrastructural
      study.
AB  - Two cases of giant cell fibroblastoma in children are presented. Histologic
      features included a dense fibrous tissue stroma with multinucleated giant cells
      lining sinusoid-like spaces. Immunohistochemical stains and electron microscopy
      provide evidence of a fibroblastic origin of the tumor cells. Ultrastructure of
      the multinucleated cells revealed segmentation of the nuclei with multiple
      centrioles, suggesting that an abnormality in the division of the tumor cells may
      be the mechanism for the formation of the giant cells.

PMID- 1369801
TI  - Expression of epidermal growth factor receptor and ERBB2 (HER-2/Neu) oncoprotein
      in prostatic carcinomas.
AB  - Expression of epidermal growth factor receptor (EGFR) and ERBB2 oncoprotein were
      studied in paraffin-embedded normal (n = 2), hyperplastic (n = 17), and malignant
      (n = 147) prostatic tissues by immunohistochemistry. Strong immunoreactivity was
      detected in the epithelial cells of all normal and hyperplastic prostates with a
      new EGFR antibody (Mab31G7). In prostatic carcinomas, the EGFR immunoreactivity
      was variable with 47% showing uniform, 39% partial, and 14% no staining. Tumors
      with partial or uniform EGFR immunoreactivity were locally more advanced and of
      higher histological grade than the EGFR-negative tumors. EGFR-positive tumors
      also had two to three times higher S-phase fraction, suggesting that EGFR
      expression conferred proliferative advantage. Patients who had either partially
      or uniformly EGFR-positive carcinomas had a worse 10-yr progression-free (p =
      0.05), overall (p = 0.03), and prostatic carcinoma-specific (p = 0.007) survival
      than those with EGFR-negative carcinomas. However, according to a multivariate
      analysis, EGFR did not have independent prognostic value. None of the normal,
      hyperplastic, or malignant prostate tissues showed clearly positive ERBB2
      immunoreactivity with MAb1 antibody.

PMID- 1369802
TI  - The use of combined in situ hybridization and immunocytochemistry to identify HIV
      infected cells in brain tissue.
AB  - It is frequently important to identify the types of cells that are infected with
      human immunodeficiency virus type-1 (HIV-1) in sections of formalin-fixed
      paraffin-embedded (FFPE) brain tissue. Currently, both immunocytochemical and in
      situ hybridization methods are used for this purpose. Combined in situ
      hybridization and immunocytochemistry results in simultaneous detection of HIV-1
      nucleic acids and proteins and allow comparison of transcriptional and
      translational events of cells infected with HIV-1 in the same section. In
      addition, this technique allows morphologic and immunologic identification of the
      cells within which in situ hybridization occurs and confirmation of the identity
      of the cells that are not hybridized. Procedures are described for use with FFPE
      brain tissue.

PMID- 1369803
TI  - Clonal Epstein-Barr virus in lymphoepithelioma-like carcinoma of the stomach:
      demonstration of viral genome by in situ hybridization and Southern blot
      analysis.
AB  - Lymphoepithelioma (LE), originally described in the nasopharynx, is an
      undifferentiated carcinoma with heavy lymphocytic infiltrate. The tumor is common
      in Southeast Asia, particularly in southern China, where the Epstein-Barr virus
      (EBV) association has been documented more consistently than in Western
      countries. Tumors histologically similar to LE have been described also in other
      anatomical sites, mostly of fore-gut origin, such as salivary gland, tonsil,
      lung, thymus, and more recently stomach. We are reporting a case of poorly
      differentiated gastric adenocarcinoma with marked lymphocytic infiltrate
      resembling LE (LE-like carcinoma) in a Chinese without evidence of nasopharyngeal
      carcinoma. In situ hybridization for EBV revealed that the tumor cells but not
      the lymphoid cells harbored the virus. Tumor cells both in syncytial and
      glandular areas were positive for EBV. By Southern blot analysis EBV was
      demonstrated in the DNA extracted from the tumor, while the adjacent normal
      gastric tissue was negative. Moreover, analysis of the EBV termini revealed a
      clonal episomal form of the virus. Our case further supports the hypothesis that
      EBV is associated with LE-like gastric carcinoma. It also strongly suggests that
      EBV infection has preceded, and thus most likely contributed to, the clonal
      expansion in this tumor.

PMID- 1369804
TI  - Oncocytic differentiation in intrahepatic biliary cystadenocarcinoma.
AB  - An intrahepatic biliary cystadenocarcinoma in a 56-yr-old white man was
      characterized by pronounced oncocytic differentiation. Grossly the tumor was a
      well-demarcated cyst filled with numerous branching papillary fronds. Most tumor
      cells had abundant granular, intensely eosinophilic cytoplasm on light
      microscopic examination and large numbers of densely packed mitochondria by
      electron microscopy. Mucin-secreting cells were also present. The patient
      returned 20 mo after resection of the primary tumor with recurrent tumor in the
      liver and widely disseminated disease throughout the abdominal cavity, and he
      died 5 mo later. Although less differentiated, the recurrent tumor again
      contained greatly increased numbers of mitochondria. The partial loss of
      oncocytic differentiation in the evolution of the present case and the benign
      nature of purely oncocytic tumors suggest that in the presence of mixed
      histologic features the potential for tumor progression is primarily determined
      by the lesser differentiated or nononcocytic component. To the best of our
      knowledge, oncocytic differentiation has not been previously described in biliary
      neoplasia.

PMID- 1369805
TI  - Surgical pathology of the head and neck.

PMID- 1369806
TI  - Correspondence re: B. M. Wagner, editorial: The self-appointed purifiers of
      science. Mod Pathol 5:101, 1992.

PMID- 1369807
TI  - Correspondence re: Frable WJ, Kempson RL, Rosai J: Quality assurance and quality
      control in anatomic pathology: standardization of the Surgical Pathology Report.
      Mod Pathol 5:102a, 1992; and Rosai J, et al: Standardization of the Surgical
      Pathology Report. Mod Pathol 5:197, 1992.

PMID- 1369808
TI  - The ethics of ignorance.

PMID- 1369809
TI  - [Psychiatrists who took shelter in French-speaking Switzerland from 1933-1945].

PMID- 1369810
TI  - Brittle diabetes in the young.

PMID- 1369811
TI  - [Growth factors in hematology].
AB  - New experimental findings on the mutual regulation of growth, differentiation and
      function of human blood cells by growth factors offer the opportunity to use
      these factors in the treatment of haematological diseases. The hitherto known
      growth factors are divided into four basic groups: 1. haematopoietic growth
      factors proper [multi-CSF (IL-3), GM-CSF, G-CSF, M-CSF, erythropoietin,
      lymphopoietin (IL-7) and megakaryopoietin (IL-11)], 2. cytokines (IL-1 to IL-11,
      TFN)., 3. other growth factors (PDGF, FGF, MGF) and 4. so-called negative
      regulators of haematopoiesis (IFN, MIP, TGF beta and IL-10), some of which
      support the differentiation of stem cells. Before growth factors can be routinely
      used in clinical work, it is essential to acquire closer knowledge of their
      interrelations, the activity of their receptors and natural or acquired
      inhibitors in vivo.

PMID- 1369812
TI  - [Hematopoietic growth factors. Biology and clinical applications].
AB  - The authors present an account of haematopoietic growth factors which include the
      stem cell factor (SCF), factors stimulating granulocytomacrophage colonies (GM
      CSF), granulocyte (G-CSF), monocytomacrophage (M-CSF) factors, erythropoietin
      (EPO) and also interleukin (IL) 1 to 11. Their main action is described as well
      as the site of action in haematopoiesis. In many of them participation in the
      pathogenesis of some diseases, incl. malignant ones, is anticipated. The
      preparation of growth factors in a recombinant-form and knowledge of their effect
      made it possible to use them in clinical practice. The authors mention possible
      indications, although in many their administration still has the character of
      clinical studies.

PMID- 1369813
TI  - [Inhibitory factors in hematopoiesis].
AB  - The author presents a short review of inhibitory factors which affect hemopoietic
      stem and progenitor cells. At present, the existence of naturally occurring
      inhibitory factors which take part in the control of hemopoiesis under
      pathological conditions in which they were detected, and probably even under
      physiological conditions, has been proved. Through their effects the inhibitory
      factors create a complex network of negative feed-back regulations. Their
      cooperation with stimulatory factors seems to be mechanism which ensures the
      balance in hemopoiesis and recovers it in the case of a disorder.

PMID- 1369814
TI  - [Familial occurrence of malignant hematologic diseases].
AB  - The cases of first-degree relatives from five families with hematological
      malignancies are described in this study. The occurrence of non-Hodgkin's
      lymphoma (NHL) and B-cell chronic lymphoblastic leukemia (B-CLL) in the first
      family, NHL and chronic myeloid leukemia (CML) in the second one, two cases of
      Hodgkin's disease (HD) in the third and the fifth one's NHL and acute
      myelomonocytic leukemia (AMML) in the fourth one observed. Several factors which
      are considered to be involved in etiopathogenesis of hematological malignancies
      (virus infection, immune defects, HL-A antigens, cytogenic features) were
      discussed. Our study confirm other previous findings, that the familial
      susceptibility results from a combination of genetic and environmental
      influences.

PMID- 1369815
TI  - [Hepatitis C virus and cryoglobulinemia].

PMID- 1369816
TI  - [The elderly with cancer: oncology's excluded patients].

PMID- 1369817
TI  - [Fatal poisoning by the rupture of intestinal bags of cocaine].
AB  - We report a case of rupture of bags filled with cocaine into the digestive
      apparatus in a young man. He carried into his digestive tract one hundred of
      small bags containing 40 g of cocaine each one. The initial clinical picture was
      characterized by sympathetic hyperactivity, rectorrhagia, and psychosis that
      evolved in 72 h to neurologic coma, convulsions, rhabdomyolysis, hyperthermia,
      hypocalcemia, hyperdynamic picture with negative blood cultures, arterial
      hypotension, syndrome of adult respiratory distress, and multiorgan failure.
      Treatment with propranolol, mechanic ventilation, barbiturates and inotropic
      agents was ineffective and the patient died 7 days after.

PMID- 1369818
TI  - [Effect of circadian rhythm on the onset of acute myocardial infarction].

PMID- 1369819
TI  - [Validation of devices and methods of measurement: agreement, yes; correlation,
      no].

PMID- 1369820
TI  - [Association of hepatitis C virus and cryoglobulinemia].

PMID- 1369821
TI  - [Historic aspects of organophosphorous compounds].

PMID- 1369822
TI  - [French pathology periodicals].

PMID- 1369823
TI  - [Apropos of the article: Palmar punctate porokeratosis].

PMID- 1369824
TI  - ["A life threatening event" in infants. Results of polysomnography and
      examination of a group of 122 infants].
AB  - Survivors of an "apparent-life-threatening-event" subsequently more often die
      from sudden infant death syndrome than others. The aim of this study was to find
      out abnormal clinical symptoms and/or polysomnographic patterns in this group of
      patients. Between January 1989 and September 1990 122 infants (mean age 13.98
      weeks) were examined after a life threatening event (mean age 9.3 weeks at the
      event). In total, 222 polysomnographic studies were performed. In 46 cases
      additional esophageal pH-metric measurements, and in 26 cases a Holter 24 hours
      monitoring were done. Seven infants were premature and had been ventilated, and 6
      were siblings of sudden-infant-death-syndrome victims. Pulmonary problems were
      identified in 7 (6%), cardiac problems in 17 (14%), 18 (15%) had neurological
      problems, and 40 (33%) showed a gastroesophageal reflux. In 14 (11%) other
      diseases were found. Only 43 (35%) infants were without pathologic findings and
      were classified as having had an "idiopathic" event. The polysomnographic studies
      showed that obstructive apnea occurred significantly more often, the maximal
      duration of apnea was longer, and the number of sudden pO2 decreases was
      significantly higher than in a group of 188 normal infants. Thus, patients having
      had an "apparent-life-threatening-event" showed a broad spectrum of abnormal
      clinical symptoms and some respiration disturbances compared to a reference group
      of infants.

PMID- 1369825
TI  - Post streptococcal glomerulonephritis co-existing with acute rheumatic fever--a
      case report.
AB  - A case of post streptococcal acute glomerulonephritis co-existing with acute
      rheumatic fever is reported. The relevant literature is briefly reviewed.

PMID- 1369826
TI  - Compendium of food additive specifications. Volume 1.

PMID- 1369827
TI  - Compendium of food additive specifications. Volume 2.

PMID- 1369828
TI  - [Eosinophilia-myalgia: new syndrome].
AB  - The eosinophilia-myalgia syndrome is a newly recognized illness that has been
      associated with the consumption of tryptophan products. We describe the clinical
      and histopathological findings and the results of biochemical analyses of
      tryptophan metabolism in patients with this syndrome and the toxic-oil syndrome
      which took place in 1981 in Spain. Symptoms and laboratory findings are similar.
      Chronic phase of EMS is characterised by long-term disability, sclerodermatous
      skin thickening, sensorimotor polyneuropathy and severe episodic myalgias. The
      development of the syndrome may result from a confluence of several factors
      including the ingestion of tryptophan, exposure to agents that activate
      indoleamine-2,3-dioxygenase, and possibly, impaired function of the hypothalamic
      pituitary-adrenal axis.

PMID- 1369829
TI  - Promotion of murine marrow alloengraftment and hematopoietic recovery across the
      major histocompatibility barrier by administration of recombinant human
      interleukin-1 alpha.
AB  - Irradiated C57BL/6 (H-2b) recipients of T-cell-depleted (TCD) BALB/c (H-2d) bone
      marrow (BM) and recombinant interleukin-1 alpha (IL-1 alpha) (1 microgram/d) had
      a significantly (P less than or equal to .006) higher 100-day actuarial survival
      rate, accelerated hematopoietic recovery, and higher levels of alloengraftment
      than a group of transplanted control mice treated identically, but given
      phosphate-buffered saline (PBS). To elucidate the mechanisms involved with IL-1
      alpha-induced promotion of alloengraftment and hematopoietic recovery, we
      performed sequential splenic FACS studies on transplanted mice and secondary
      transfer studies in syngeneic mice given IL-1 alpha or PBS. Splenic phenotyping
      showed that recipients of IL-1 alpha had a higher proportion of donor
      granulocytes (52% v 19%) as compared with PBS controls as early as 7 days after
      bone marrow transplantation (BMT). On day 11 post-BMT, recipients of IL-1 alpha
      had a more than fourfold increase in splenocyte number, which included a higher
      percentage (90% v 59%) of donor cells, especially donor granulocytes (52% vs
      32%), and a sevenfold increase in donor T cells as compared with controls. Host T
      cell numbers were not affected. Taken together, these data suggest that IL-1
      alpha stimulated bipotential (myeloid and lymphoid) donor cell engraftment. In a
      syngeneic BMT system, administration of IL-1 alpha resulted in a higher incidence
      of survival when recipients were transplanted with BM cells, indicating that IL-1
      alpha administration probably either expanded or potentiated engraftment of a
      committed progenitor cell pool. Secondary transfer experiments using marrow from
      IL-1 alpha-treated mice showed that the number of day 12 colony-forming unit
      spleen (CFU-S) cells was unaltered compared with untreated control mice,
      suggesting that more primitive, albeit committed, hematopoietic progenitor cells
      were not affected. We also examined the potential additive effects of IL-1 alpha
      and granulocyte-macrophage colony-stimulating factor (GM-CSF) administered in
      combination (for 14 days). Mice receiving a suboptimal amount of IL-1 alpha along
      with GM-CSF had significantly higher levels of donor alloengraftment (92%) with
      superior hematopoietic recovery, as compared with mice receiving either IL-1
      alpha (57%) or GM-CSF (18%) alone.

PMID- 1369830
TI  - [Evaluation of changes in microcirculation dynamics of a free muscular flap
      submitted to many hours of ischemia. In vivo experiments].
AB  - The paper presents the influence of progressive ischemia on the rat cremaster
      muscle isolated on neurovascular pedicle. Direct in vivo microscopic observations
      revealed destructive changes of microvessels progressing from periphery to the
      base of the flap along with increasing in time ischemia. Since there was
      absolutely no return of circulation after 6 hours of ischemia this period was
      recognized as critical ischemia for survival of the free muscular flap.

PMID- 1369831
TI  - [Observation of microcirculation in the free muscular flap during critical
      ischemic conditions. In vivo experiment].
AB  - The influence of 6 hours ischemia on the microcirculation in the rat cremaster
      muscle isolated on neurovascular pedicle is presented. Microscopic observations
      of the microcirculation revealed gradual destruction of microvessels beginning in
      the 4th hour of ischemia. The changes in condensation, structure and colour of
      the vessels were progressive in time and after 6 hours of ischemia no return of
      the circulation was possible. Additional 2 hours of observation revealed no
      reperfusion, so destructive changes after 6 hours proved to be irreversible.

PMID- 1369832
TI  - [The relationship of radiologic bone structure image to mineral content and
      morphometric parameters of trabecular bone].
AB  - Radiographic, mineralogic and histomorphometric investigations of the distal
      radial metaphyses were performed in a group of 57 men who sustained sudden death.
      The radiographic image of bone structure was assessed by nude eye and with
      computerized analyses of the microdensitometric curves. Mineral in bone specimens
      content was estimated by Dulce method. Trabecular mineralized bone area (Vmin),
      osteoid area (Vos) and trabecular width (dt) were measured on undecalcified
      sections. Decrease of bone mineral content and Vmin were noted with the age of
      those investigated. This process affected the radiographic image of bone
      structure. The radiographic picture of bone structure depends mostly on the
      mineral content and to a smaller extent on histomorphometric parameters.
      Microdensitometric measurements make objective assessment of bone structure on
      the radiograph possible.

PMID- 1369833
TI  - [Mineralization phenomena in the area of long bone fracture wound healing].
AB  - Mineralization changes in the area of fracture healing in experimental rabbits
      were monitored during 28 days of observation. The changes were evaluated with the
      aid of microscopy in the polarized light, scanning microscopy, infrared
      spectroscopy and roentgenographic microanalysis in 7, 14, 21, and 28th day of
      healing process. Mineralization was found to be parallel to the increase of
      collagen quantity. In the course of healing an arrangement of atom structure of
      the phoshate takes place. Increasing mineralization is indicated not only by
      growing values of Ca and P in newly formed bone but also by Ca/P ratio
      approaching normal values in the final stage of healing. Despite of clinical and
      radiological features of bony union the process of mineralization is not yet
      completed. By the 28th day of healing the mineral structure of bone is still
      remarkably porous resembling cancellous bone. Cortical bone formation occurs on
      the basis of cancellous bone by organization of the osseous trabeculae.

PMID- 1369834
TI  - [Index of the diaphyseal cortex and mechanical strength of the femur in
      experimental studies].
AB  - The mechanical strength at bending was examined in 26 femoral bones prepared from
      human corpses. The obtained data was compared with the cortical index (CI). The
      study demonstrates high correlation between CI and mechanical strength of the
      corpus as well as the collum of the examined bone, which means that CI is a good
      criterion in assessing biological age of the bone. Our study confirms previously
      made observations that revealed a considerable usefulness of CI determined in X
      rays, for the estimation of osteoporosis advancement in long bones and their
      mechanical strength.

PMID- 1369835
TI  - [Developmental anomalies of the cranio-cervical region].
AB  - The paper presents in compact form some anomalies of craniovertebral region; 77
      cases of minor and 30 cases of major anomalies were reported. The aim of this
      paper is to indicate morphological heterogeneity of these anomalies and necessity
      of differentiation in cases of cranio-cervical injuries.

PMID- 1369836
TI  - [Usefulness of reduction and fusion in the management of spondylolisthesis].
AB  - The results of treatment of spondylolisthesis in 72 patients by reduction with
      the use of Harrington rods and circumferential fusion were reported. In
      dysplastic spondylolisthesis 75% satisfactory results and 83.4% spinal fusions
      were achieved, in stenotic spondylolistheses 80% and 85% respectively. The
      influence of operation on sacral bone position against lumbar spine could not be
      accurately traced with the aid of Wiltse radiological criteria. The authors
      consider arthrodesis "in situ" as insufficient procedure, especially in
      dysplastic type of spondylolisthesis. They recommend addition of anterior fusion
      that retains and stabilizes reduction being limited to single motoric unit of the
      spine.

PMID- 1369837
TI  - [Epidemiologic analysis of spinal injuries resulting from high falls].
AB  - A series of 1365 patients treated between 1965 and 1987 because of spine injury
      resulting from the fall from the height was analysed. A fall from the height may
      cause hyperflexion, axial loading or hyperextension type of injury. Hyperflexion
      injury occurs usually after fall from horsedrawn wagon, scaffold, roof or pillar.
      Axial loading injuries dominate in falls from the ladder, tree, suicidal jumps
      and falls from lower height. There is remarkable correlation among the height of
      the fall, degree of nervous system injury and results of management.

PMID- 1369838
TI  - [Open injuries of the spinal cord].
AB  - A series of 26 patients with stab, gun shot or other injury was presented. Good
      prognosis in partial spinal cord injury due to the stab wound was pointed out.
      Gun shot wounds usually resulted in total paresis even with little damage to the
      bony structures.

PMID- 1369840
TI  - [Stabilization of the fractured odontoid process with a compression screw].
AB  - The surgical technique for fractured dens stabilization with the use of
      compression screws was discussed. This method suggested by Bohler, in certain
      modification due to the equipment shortage, was applied in 8 patients operated
      shortly after injury has occurred. Relatively simple operative technique, good
      results, possibility to avoid head movements restrictions usually associated with
      posterior approach procedures makes this method valuable in certain cases
      especially in centers experienced in anterior approach spine surgery.

PMID- 1369839
TI  - [Gunshot wound of the lumbar spine].
AB  - A case of 20 years old patient with the gunshot injury of the spine was
      presented. The bullet has stuck in the spinal canal at L3-L4 level causing no
      neurological disturbances. It was removed in our department gunshot wounds to do
      this in district hospital. No complication occurred in the postoperative course.

PMID- 1369841
TI  - [Avascular necrosis of the hip in radiologic images during treatment using the
      Freyka pillow for congenital hip dislocation].
AB  - Radiological picture of 823 hips in 636 children treated with the use of Freyka
      pillow between 1972 and 1976 was assessed. Avascular necrosis of the proximal end
      of the femur was found in 113 cases. The older the child was at the beginning of
      treatment the highest were the chances for developing avascular necrosis, but
      more serious changes were found in younger children. In the hips with greater
      initial dislocation changes were more frequent. A comparison between hips treated
      with Freyka pillow and those treated with different methods as to frequency of
      avascular necrosis was difficult due to the lack of uniformity in criteria for
      both diagnosis and assessment of the results.

PMID- 1369842
TI  - [Late assessment of the hip joint treated with the Freyka pillow without
      complications for congenital dysplasia and dislocation].
AB  - Clinical and radiological assessment of 504 hips in 389 patients of 10 to 21
      years of age (13 years 10 month on average) has been carried out. The patients
      were treated by Freyka pillow in the childhood. Those with no reduction achieved
      primarily and operated on because of residual dysplasia as well as patients with
      severe avascular necrosis were excluded from this study. In 99% of the hips no
      clinical abnormality was found except for the change of rotation range--decreased
      external rotation. Radiographic assessment revealed 60% excellent results and 35%
      good ones with dominant residual feature of increased anteversion of the femoral
      neck. Remaining 5% were rated as fair--these were the cases that should have been
      operated on at a suitable time.

PMID- 1369843
TI  - [Transient synovitis of the hip joint in children].
AB  - Etiology, pathology, clinical and radiological symptoms, and course of transient
      synovitis of the hip was discussed on the basis of authors observation of 144
      children as well as on literature. It was found that unloading the joint by
      staying in bed with slightly flexed hip led to subsidence of pain and return of
      full range of movement in 10 to 21 days. Only in older children the symptoms may
      persist 4 to 5 weeks. Permanent consequences of transient synovitis of the hip as
      elongation of the extremity and coxa magna in X-ray pictures are rarely observed.
      Transient synovitis of the hip seems not to have etiological links with Perthes
      disease.

PMID- 1369844
TI  - [Nonspecific arthritis of the hip in children].
AB  - Clinical and radiological picture as well as pathological classification of non
      specific hip arthritis in children were presented after reviewing 100 cases and
      on the base of literature. Different course and sequel of different pathological
      types of hip arthritis were pointed out with emphasis on suppurative arthritis of
      the hip. The management of all types of hip arthritis was discussed. The
      necessity of surgical drainage of the joint in the first 5-7 days of suppurative
      arthritis as the only measure to prevent irreversible hip destruction was
      underlined. The method should become popular among pediatric surgeons and
      pediatricians who are the first ones to take care of a child in the early stage
      of disease.

PMID- 1369845
TI  - [Consideration of the legitimacy for connecting the opposite femoral head and
      neck in juvenile slipped capital femoral epiphysis].
AB  - Forty seven patients were treated because of slipping of the capital femoral
      epiphysis, in 23 patients (48.9%) both hips were involved. In one third of these
      cases both hips were diagnosed at the same time, in one third second hip was
      diagnosed from 6 to 24 months later, in one third only late diagnosis of juvenile
      symptom free--thus the late diagnosis. In 18 hips slipping was less than 30
      degrees, in 5 hips more than 30 degrees. On the basis of authors own experience
      and review of literature the conclusion was made to fix with K--wires epiphysis
      of the opposite hip as a prophylaxis against slipping.

PMID- 1369846
TI  - [Long term results of total hip arthroplasty in patients with ankylosing
      spondylitis].
AB  - The results of total hip arthroplasty with the use of 5 different types of
      prostheses in 63 hips of 38 patients were presented. The range of follow up was
      from 7 to 14 years. The evaluation was done with the aid of M. d'Aubigne--Postel
      criteria and radiological assessment. Patients opinion and his ability to work
      was taken into consideration. The pain was reduced most significantly. Remarkable
      improvement was found in the gait and in the range of hip motion. In 24.5% of
      patients possible, probable or evident radiographic loosening was found. Ectopic
      ossifications of different degree were found in 38.8% of patients, mostly in hips
      previously operated on or severely destroyed. Ankylosing hips improved in
      movement to lesser extent. No deep infection was observed in early or late follow
      up.

PMID- 1369847
TI  - [Should trochanteric osteotomy be performed during total hip replacement?].
AB  - Advantages and disadvantages of trochanteric osteotomy were discussed. 716 total
      hip arthroplasties were performed in 594 patients. Trochanteric osteotomy was
      done in 79 hips (11%) of 68 patients: 39 cases of rheumatoid arthritis, 17 cases
      of ankylosing spondylitis, 9 cases of osteoarthritis and 3 cases of various
      conditions. In 73 hips the trochanter was reattached by Charnley, Coventry or
      Amstutz method; in remaining cases an original method was used. 42 hips in 36
      patients were followed up. The results were evaluated on the basis of clinical,
      radiographic assessment and opinion of the patient. Trochanteric non-union was
      found in 3 hips (7.1%), delayed union in 2 cases (4.7%), the wire loop was broken
      in 6 hips (14.2%) with no disturbance of trochanteric union. The authors
      recommend Trochanteric osteotomy only in cases of difficult access to the joint
      or in order to prevent soft tissue damage in instances of difficult anatomic
      conditions.

PMID- 1369848
TI  - [Evaluation of the hip joint after Kee-Farrar total hip arthroplasty from the
      aspect of certain clinical biomechanical criteria].
AB  - Hundred hips in 84 arthritic patients after Mc Kee-Farrar total hip arthroplasty
      were reviewed. Biomechanical measurements in operated, arthritic non-operated and
      normal hips were compared. The moment of adductive forces, adductive forces, the
      strength of abductors, Hamacher-Roesler index and Wozny coefficient were
      determined. In nonoperated arthritic hips these measurements were abnormal. They
      were close to normal values in operated hips with negative Trendelenburg sign.

PMID- 1369849
TI  - [Resection of the obturator nerve for analgesic treatment of degenerative
      deforming changes of the hip joint].
AB  - Resection of the obturator nerve in hip joint arthritis can eliminate or decrease
      pain depending on the obturator nerve share in the hip joint innervation. From
      1986 to 1988 34 obturator neurectomies were performed in painful hip arthritis
      patients with temporary or permanent contraindications for hip arthroplasty. In
      21 from 30 patients followed-up at least 3 months partial or total relief of pain
      was found. Extrapelvic obturator neurectomy technique and indications for this
      procedure were presented.

PMID- 1369850
TI  - [Total knee arthroplasty with GSB endoprosthesis (introductory information)].
AB  - The construction of GSB prosthesis and surgical technique was presented. The
      prosthesis having no fixed axis enables flexion and extension as well as shifting
      and rolling. Unlike the other systems GSB implantation does not require vast
      resection of femoral and tibial condyles. This is very important in case of
      failure and necessity of removal of the prosthesis--the revision arthroplasty or
      arthrodesis does not result in great shortening of the extremity. GSB prosthesis
      was implanted by the authors in 25 knees of 23 patients. The average follow up
      was 9 months. In all cases results were good, complications were not observed.
      The authors conclude that GSB prosthesis deserves wider propagation in surgical
      treatment of advanced destructive changes in the knee, especially in rheumatoid
      patients.

PMID- 1369851
TI  - [Longterm results of McIntosh hemiarthroplasty of the knee in patients with
      rheumatoid arthritis of the knee].
AB  - A series of 35 knees operated on between 1967 and 1977 was reviewed. The follow
      up of 5 years or longer revealed over 40% of excellent and good results. The
      analysis of over 50% of poor results is suggestive of inadequate indications for
      hemiarthroplasty of the knee. In authors opinion Mc Intosh procedure should be
      still performed providing the indications are very accurate.

PMID- 1369852
TI  - [The hinge prosthesis in treatment of rheumatoid arthritis and osteoarthritis of
      the knee].
AB  - Fifty two knee arthroplasties with hinge prostheses of guepar and rotating-hinge
      types were performed in treatment of rheumatoid and osteoarthritis over 12 years.
      With the use of point scale 49 results were rated good or fair, 3 results were
      poor.

PMID- 1369853
TI  - [Value of clinical examination and arthrography in diagnosis of meniscal lesions
      in light of arthroscopic results].
AB  - The results of clinical, arthrographic and arthroscopic examination in the group
      of 120 patients with suspected meniscal lesion have been compared. In the
      clinical examination the McMurray and the Apley tests revealed a good correlation
      with meniscal tears. Arthrography was found to be in accordance with arthroscopy
      in 62%. The results were falsely negative in 15% and falsely positive in 25% of
      patients respectively.

PMID- 1369854
TI  - [Arthroscopy in diagnosis and treatment of traumatic and nontraumatic disorders
      of the knee joint].
AB  - A series of 325 diagnostic and operative arthroscopic procedures were reviewed-
      the growing importance of this technique was underlined. An open meniscectomy was
      performed in 235 cases after diagnostic arthroscopy. In 45 cases meniscal flap
      was removed arthroscopically. In 7 cases chondral or osteochondral loose bodies
      were removed, in 5 cases the hypertrophic synovial fold was cut, in 3 cases
      staples or fixation screws were removed and 3 diagnostic biopsies were carried
      out. No significant complication was observed. It was stated that arthroscopy
      makes diagnostics more precise, enables performing some operations without
      opening that joint, reduces of treatment and its costs.

PMID- 1369855
TI  - [Elbow arthroplasty in patients with rheumatoid arthritis of the joint].
AB  - Fifteen elbow arthroplasties were performed in 15 rheumatoid patients between
      1976 and 1988. In 2 cases fascial interposition was abandoned. The indications
      for surgical treatment were presented and the results analysed. Ten were rated
      good, 4 fair and 1 poor.

PMID- 1369856
TI  - [Outcome of surgical treatment in patients with rheumatoid wrist arthritis].
AB  - The results of tendon synovectomies, synovectomies, arthrodeses and tendons
      reconstructions in 117 wrists of 83 rheumatoid patients are reported. Eighty nine
      percent of good and fair results prove correct selection and timing of surgical
      treatment.

PMID- 1369858
TI  - [Pollicization of the index finger in posttraumatic thumb defects].
AB  - Four patients with pollicization of the index finger were presented. In 3 cases
      of subtotal amputation the results were rated as excellent or good. Good blood
      supply, innervation and movement in transferred index finger indicate safety and
      reliability of this procedure.

PMID- 1369857
TI  - [Surgical treatment of metacarpo-phalangeal joints in patients with rheumatoid
      arthritis].
AB  - The results of surgical treatment of 195 metacarpo-phalangeal joints in 132
      rheumatoid patients were evaluated. The indications for each of three operative
      methods were presented with clinical assessment and Larsen, Dahle, Eek scale of
      radiological changes taken into consideration. The results of 137 synovectomies,
      32 joint replacements and 24 arthroplasties in 88% were rated as good and fair.
      The advantages of early synovectomy as well as joint replacement in advanced
      arthritis were underlined.

PMID- 1369859
TI  - [Contemporary management of Dupuytren disease].
AB  - The principles of management of Dupuytren contracture of the hand were discussed
      on the base of world literature. Nonsurgical treatment proved to be totally
      ineffective. There are precise indications for surgical procedures; the range of
      the operation should be chosen individually. Neglecting these principles leads to
      extended postoperative course and makes the results of treatment far from being
      ideal.

PMID- 1369860
TI  - [Treatment of neoplastic bony metastasis].
AB  - The means and results of treatment of 113 patients with neoplastic metastases
      into the bone were presented. Conservative and surgical treatment was employed in
      65 and 48 patients respectively. The use of bony cement and of connecting
      elements (so called neoplastic prostheses included) have broaden possibilities of
      surgical treatment. The pain was reduced usually even eliminated in all the
      patients. Most of them regained function of the extremity involved, some of them
      returned to their previous occupation. The longest survival period was observed
      in patients with kidney cancer metastases.

PMID- 1369861
TI  - [Early surgical treatment of congenital club feet].
AB  - Subtalar release was carried out in 70 feet of 60 children in the first 3 months
      of their life. Patients with rigid congenital club feet not responding to
      conservative treatment were selected. The average age of patient at the operation
      was 64 days. Using criteria by Main 24.3% results were rated as excellent, 61.4%
      as good that is feet with correct shape and function. The importance of age at
      the operation and the range of surgical procedure were discussed.

PMID- 1369862
TI  - [Vascularization in congenital hypoplasia of the leg in children].
AB  - On the basis of digital subtractive angiography (DSA) arterial vascularization of
      lower extremities of six children with congenital hypoplasia of the leg has been
      studied. Four of our patients had fibular aplasia and anterior bowing of the
      tibia. One child had congenital bowing of the leg, and one had congenital
      pseudoarthrosis. An obstacle for contrast agent passage was found in every case
      at different levels of both anterior and posterior tibial arteries, in one case
      additionally segmental occlusion of popliteal artery was observed. These vascular
      anomalies combined with musculoskeletal hypoplasias are suggestive of
      developmental disturbances from intrauterine life. According to the authors they
      are responsible for frequent failures in surgical treatment of fibular aplasia
      with anterior bowing of the tibia and of congenital pseudoarthrosis of the leg.

PMID- 1369863
TI  - [Correction of tibial varus deformity due to Blount disease using an epi
      metaphyseal distraction].
AB  - The possibility to correct tibial varus deformity due to Blount disease by epi
      metaphyseal distraction was presented. The correction was achieved in 2 patients;
      in one of them leg length discrepancy was eliminated. The method is not invasive,
      offers continuous rehabilitation and a possibility of equalization of the
      extremities.

PMID- 1369864
TI  - [Intramedullary osteosynthesis of tibial shaft fractures].
AB  - Thirty seven patients with fracture of tibia were treated by closed method
      intramedullary osteosynthesis with Kuntscher nail (22 cases) and with elastic
      rods designed by the authors. Complete bony union was achieved on average after
      30 and 47 weeks in fresh and old fractures respectively. There was 1 case of mild
      osteitis after second osteosynthesis and 1 patient with multiple trauma has died.
      No union disturbance was observed.

PMID- 1369865
TI  - [Secondary dislocations in fractures of the distal end of the radius].
AB  - In the group of 31 patients treated by immobilization of the forearm we observed
      71% of secondary dislocations and in group of 46 with the full-arm plaster 65% of
      secondary dislocation occurred. In the group of 20 patients with the full-arm
      plaster and the X-ray done between the 7th and 10th day after reduction to
      correct possible dislocation, followed always by the new, similar plaster cast,
      we observed 40% of secondary dislocations. Whenever the full-arm plaster was used
      Sudeck syndrome was observed very rarely. No direct relationship between kind of
      plaster used and the degree of shortening of the radius length after healing of
      the fracture was found. Comminuted fractures and osteoporosis are in favour for
      secondary dislocations.

PMID- 1369866
TI  - [Treatment of the infected pseudoarthrosis of the tibia by the Harmon method].
AB  - The principles of treatment of tibial pseudoarthroses complicated by skin and
      soft tissue loss with the use of cancellous bone grafts from posterolateral
      approach to the tibia by Harmon method were discussed. The detailed surgical
      technique was presented. Management of 3 patients that resulted in bone union was
      described.

PMID- 1369867
TI  - [Results of treating pseudarthrosis and leg bone defects caused by osteitis].
AB  - The results of treatment of 17 patients--8 cases of leg bones defect due to
      osteitis and 9 cases of leg pseudoarthrosis has been presented. The
      osteosynthesis of the fragments was done with the use of Zespol fixator. In 14
      patients the lesion has healed and satisfactory function of the extremity was
      restored.

PMID- 1369868
TI  - [Pedicle bone grafting in treatment of bone union disorders after femoral neck
      fracture].
AB  - Clinical and radiological assessment of 8 patients operated because of femoral
      neck pseudoarthrosis or delayed union proved the pedicle bone grafting to be very
      useful method, especially in young patients. Surgical reconstruction of femoral
      neck with the use of pedicular graft (Judet--Chacha) resulted in all the patients
      in absence of pain; satisfactory range of movement has been restored in operated
      hip. Bone union has been achieved in 7 from the 8 operated patients that is in
      all the cases of posttraumatic union disorders. However, we failed in total
      reconstruction of anatomy and the radiographs revealed osteoarthritis of the
      joint.

PMID- 1369869
TI  - [Tactics in management of coccygodynia].
AB  - The results of treatment of 160 patients with coccygodynia were analysed. The
      condition was caused by contusion, fracture or dislocation of coccygeal vertebrae
      or excess of osteochondral tissue around the coccyx. The patients were treated
      conservatively and surgically, 56 and 104 respectively. In 94 cases (50,3%) of
      surgically treated complete recovery was achieved. Surgery should be undertaken
      in cases not responding to conservative measures.

PMID- 1369870
TI  - [The issue of lower limb amputations in vascular diseases].
AB  - A series of 363 amputations in 335 patients treated between 1979 and 1988 because
      of chronic peripheral vascular disease was reviewed. In years from 1979 to 1988
      3500 vascular surgical procedures were carried out. In 217 cases (6,2%)
      subsequent amputation was necessary. Previously, from 1962 to 1978 it had
      occurred in 8,5%. The authors experience is indicative of limb vascularization as
      decisive factor in choosing the level of amputation. In high aortoiliac arterial
      occlusion a vascular procedure is carried out, resulting in good blood supply of
      the stump allowing lowering the level of amputation and shortening recovery
      period.

PMID- 1369871
TI  - [Stresses in self-compressing plates used for joining bone fragments].
AB  - The analysis of the state of stresses in the auto-compression plates after
      different stages of joining has been carried out. Distinct differences in the
      values of stresses in the specific zones of plates were detected. The highest
      level of stress was located near the holes, in the areas where prebending takes
      place. The main reason of the loss of the ability to carry introduced compressing
      forces in the joint and possibility of cracks initiation in plates during the
      operation has been clarified.

PMID- 1369872
TI  - [Myocutaneous flap from the tensor fasciae latae in treatment of trochanteric
      decubitus ulcers].
AB  - The paper presents paraplegic patient after L1-L9 subluxation due to the spine
      injury. Excision of trochanteric decubitus ulcer covered with the tensor fasciae
      latae myocutaneous flap gave permanent result.

PMID- 1369873
TI  - [Avulsion injury of spinal nerve roots in part of the lumbosacral spine].
AB  - A case of 40 years old male with left sided avulsion injury of L5, S1 nerve roots
      due to severe trauma. Diagnosis was confirmed with CT and radiculography. The
      presence of prolapsed sheath of the avulsed root in radiological examination
      combined with clinical picture establishes correct diagnosis.

PMID- 1369874
TI  - [Sacrum fracture associated with neurologic complications].
AB  - A care of the patient, aged 39, who sustained a fracture of the sacrum
      complicated by compression of the roots L5 and S1 is reported. Surgical treatment
      on root decompression was performed. Following 9 months neurological signs
      subsided, but some intermittent low back pain persisted.

PMID- 1369875
TI  - [Long-term results of treating histiocytosis X of the spine].
AB  - A series of 38 children and juveniles with eosinophilic granuloma located in 44
      vertebral bodies was treated. The diagnosis was based on typical radiographic
      appearance, bone marrow examination and histology in cases where the lesion was
      surgically resected. Management consisted mainly of immobilization and unloading
      of the spine for 2-3 years. Since 1972 in order to shorten this period posterior
      arthrodesis of 3 vertebral bodies in thoracic spine and 2 vertebral bodies in
      lumbar spine by Albee-Gruca method is performed. Radiotherapy was applied in 1
      case. In most of the cases full or partial regeneration of the vertebral body was
      achieved; the height was restored in 76% on average. The extent of regeneration
      was higher in younger children and in lumbar and cervical spine possibly because
      of lordosis in these segments.

PMID- 1369876
TI  - [Surgical procedures for bone neoplasms in children].
AB  - The treatment of 40 patients with bone tumors have been presented. The primary
      tumors were located in the following sites: femur (14), tibia (8), fibula (4),
      humerus (4), scapula (1), clavicle (2), pelvis (5), hand (1). Investigated group
      were: osteosarcoma (18), Ewing's sarcoma (14), chondrosarcoma (2), fibrosarcoma
      (1), synovial sarcoma (1), chondroblastoma (4). In the most frequent malignant
      bone tumors, osteosarcoma and Ewing's sarcoma, unified management was adapted.
      The treatment was initiated with multidrug chemotherapy and followed by surgery
      or radiotherapy (Ewing's sarcoma) of the primary site. Surgery was performed in
      30 cases: 19 mutilating operations because of the broad local invasion, 11
      conservative surgical procedures (limb -- salvage operations). Satisfactory
      oncological and functional effect can be achieved after limb-salvage surgical
      procedures in the cases of localized, especially semimalignant bone tumors.

PMID- 1369877
TI  - [Remarks concerning diagnostic principles and early treatment of congenital hip
      dislocation].
AB  - Principles of early diagnosis and treatment of congenital dislocation of the hip
      are presented. The clinical course, complications and results of treatment by
      Frejka pillow are reported. Indications for surgical treatment in cases of
      failure by conservative management, as well as in cases of deficient rebuilding
      of the hip are discussed.

PMID- 1369878
TI  - [Ultrasound diagnostics of the spine].
AB  - A short delineation of contemporary ultrasound applications, its possibilities
      and limitations in diagnostics of the spine and related structures is presented.
      Ultrasound has an established position in diagnosing fetal spinal defects and
      dysraphic syndromes especially in children. It is also an important method of
      intraoperative imaging. Ultrasound can be used in diagnosing sciatica and in
      identification of pathological spondylosis cisterns.

PMID- 1369879
TI  - [Traumatic hip dislocation in children].
AB  - Three children aged 7, 9 and 11 were treated because of traumatic dislocation of
      the hip. There was one case of anterior and two cases of posterior iliac
      dislocation. The reduction was performed under general anaesthesia directly after
      admission. In two children derotational shoe for 6 weeks and a plaster for 3
      weeks in third case were used in after treatment. The unweighing of the limb was
      maintained for 6 weeks more. Subsequently, the gradual weight bearing was
      allowed. Radiographic examination of two children 1.5 and 3.75 years after injury
      revealed normal hip joints. There was no restriction of physical activity of
      these children.

PMID- 1369880
TI  - [Nonspecific osteogenic arthritis of the hip].
AB  - Osteogenic arthritis of the hip in children depending on the localization of the
      primary focus of infection can be classified into three types of femoral,
      acetabular and pelvic origin. These types differ as to the pathology as well as
      clinical course of the disease. Diagnostics and treatment is discussed. It was
      found that improper treatment in the early stage led to the chronic form of the
      disease. Clinical and radiological picture of osteogenic hip arthritis as well as
      its treatment is discussed on the basis of 125 cases reviewed. Different sequel
      to osteogenic hip arthritis depending on pathological origin, stage of the
      disease and method of treatment were pointed out.

PMID- 1369881
TI  - [Evaluation of knee joint function after fracture of the patella].
AB  - Clinical assessment of the function of the knee joint after surgically and
      conservatively treated fracture of the patella was carried out. On the basis of
      C. Ranawat criteria it was found that regardless the method of treatment applied
      restriction of the joint function was expressed mainly by limited range of motion
      and by weakening of the knee extensors. The results of surgical and conservative
      management are similar. The best results of treatment for fracture of the patella
      were achieved in patients operated with the use of wire loop-cerclage.

PMID- 1369882
TI  - [Radiologic analysis of the patello-femoral joint after treatment of patella
      fracture].
AB  - Anatomical condition and congruence of the patello-femoral joint after
      differently treated fracture of the patella was assessed on the basis of
      roentgenometric analysis of radiographs of 39 patients. The best situation was
      found in surgically treated cases with the use of the wire loop (cerclage), less
      favorable in patients managed conservatively and the worst in patients operated
      after Weber.

PMID- 1369883
TI  - [Surgical treatment of spastic flatfoot using Gorynski's method].
AB  - After failure analysis in so far applied surgical treatment of spastic flatfoot
      the technique of synthesis of already existing procedures have been offered. Foot
      alignment is achieved by the reduction of the talus in relation to the calcaneus
      that is secured by bony graft after Grice and front-rearfoot alignment with
      Kirschner's wire fixation through calcaneus to talus and secondly cuboid to
      calcaneus. The muscular balance is provided by elongation of the calcaneal tendon
      and transposition of peroneal brevis tendon into tendon of tibialis posterior
      muscle. In the after treatment long cast immobilization is after 3 weeks replaced
      by walking cast for next 9 weeks. This management proved to be clinically
      successful for 15 years.

PMID- 1369884
TI  - [Evaluation of surgical treatment for spastic flatfood using Gorynski's method].
AB  - The assessment of surgical treatment of 100 spastic flatfeet by Gorynski method
      was presented. After average follow up of 7 years restoration of correct shape of
      the foot was found in 86 cases.

PMID- 1369885
TI  - [A trial of ultrasonographic use for evaluating leg lengthening].
AB  - Modified de Bastiani method of callotasis with Wagner apparatus was used as a
      lengthening procedure of 4 femurs and 1 tibia. The ultrasonography was applied to
      measure the degree of distraction, to determine the eventual axial deviation of
      the bone ends and to follow up the callus formation in the gap. The obtained
      results were compared with radiography.

PMID- 1369886
TI  - [Apert Syndrome--orthopedic aspects and treatment outcome].
AB  - Several years follow up of 3 patients aged from 4 to 14 years with
      acrocephalosyndactyly of Apert Syndrome type is described. Functional evaluation
      of the hands was performed before the onset and after completion of treatment.
      Psychological tests run since the beginning of treatment were analyzed. In all
      cases remarkable improvement of function and shape was achieved, but progressive
      bony changes within phalanges negatively influence all over results.

PMID- 1369887
TI  - [Torsion and rotation of apical vertebrae and thoracic deformity in idiopathic
      thoracic scoliosis in computer tomography].
AB  - CT examination of 9 patients with primary thoracic right sided scoliosis aged
      from 13 to 19 years (15 years and 4 months on an average) was carried out. The
      angle of curvature (Cobb method) ranged from 38 degrees to 99 degrees (68 degrees
      on an average). Rotation of the apical vertebra was measured and torsion
      evaluated. Rotation ranged from 5 degrees to 28 degrees (17 degrees on an
      average). No relation among rotation, angle of curvature and size of the hump was
      found. The directions of rotation and torsion were opposite. At the apex of
      curvature due to torsion the end of spinous process was deviated towards the hump
      but the vertebrae into opposite direction.

PMID- 1369888
TI  - [Congenital hemihypertrophy].

PMID- 1369889
TI  - [Fracture of both humeral bones after electrocution].
AB  - A case of 58-years-old male electrocuted with 220 V/50 Hz voltage is presented.
      The electrocution resulted in fracture within proximal end of both humeral bones.

PMID- 1369890
TI  - [A case of carpal tunnel syndrome caused by an abnormality of the palmaris longus
      muscle].
AB  - The authors present a rare case of carpal tunnel syndrome caused by accessory
      head of palmaris longus muscle of a soft tissue tumor appearance. Clinical
      examination was typical for carpal tunnel syndrome. X-ray revealed no bony
      abnormalities. An ultrasound aided diagnosis, that was finally confirmed intra
      operatively and by histopathology.

PMID- 1369891
TI  - [Principles of forming a diagnosis in orthopedics and orthopedic-trauma].
AB  - The rules of writing accurate and profound-diagnoses in orthopedics and
      traumatology were presented. The most common mistakes were pointed out. An
      attention was paid to the eponyms. Latin language and correct vocabulary.

PMID- 1369892
TI  - [A selection of entries and definitions concerning the hand].

PMID- 1369893
TI  - [What is research?].
AB  - The issue of research is presented in this paper. It is classified and
      characterized. The factors that motivate physicians to undertake research are
      pointed out as well as danger of superficial or even dishonest attitude towards
      this problem.

PMID- 1369894
TI  - [Electrostimulation in treatment of scoliosis].
AB  - The efficiency of electrical stimulation in the treatment of idiopathic scoliosis
      was assessed on the basis of 95 patients reviewed. In 63% of cases an improvement
      or inhibition of progression of the curvature was achieved. The infantile and
      juvenile positive therapeutic effect was found in 70% patients, providing the
      onset of the therapy took place before the tenth year of life. Adolescent
      scoliosis were affected by this kind of therapy only to the very little extent.

PMID- 1369895
TI  - [The value of Sowinski coracoid-plasty for recurrent dislocation of the
      shoulder].
AB  - The value of Sowinski coracoplasty for recurrent, trauma related dislocation of
      the shoulder was evaluated on the basis of multidirectional clinical, Xray, CT
      and ultrasound examinations in 15 patients operated on between 18 and 40 years of
      age. Good results were achieved in 14 cases after 2-14 years follow up. In one
      case of epileptic patient 4.5 years after surgery traumatic dislocation of the
      shoulder occurred with a fracture of incorporated bony graft. The authors have
      proved the coracoplasty performed to be efficient in preventing recurrent
      dislocation of the shoulder by means of creating new biomedical conditions around
      the joint. The bony graft by elongation of the coracoid process of ca 35 mm and
      change in its alignment imposes strong mechanical support for the head of the
      humerus and indirectly makes the acetabulum deeper. The graft located above
      anterior rim of the acetabulum increases the tension of subscapular muscle and
      stabilizes the capsule thus aiding to the stability of the joint. In 4 cases some
      adhesions between the graft and subscapularis muscle have slightly restricted
      external sotation of the shoulder.

PMID- 1369896
TI  - [Use of arthroscopy for knee joint diagnosis in children].
AB  - Diagnostic arthroscopy in 25 patients below 18 years of age was performed.
      Clinical diagnosis was confirmed in 48% of cases. The differences occurred mainly
      in diagnoses of menisceal injuries. In 10 cases (40%) arthroscopy indicated no
      need for further surgical treatment. In the author's view more frequent use of
      arthroscopy in diagnosing knee problems in children is justified.

PMID- 1369897
TI  - [Evaluation of long term results of treating patellar fractures with polyester
      sutures].
AB  - The late results of patellar fractures treatment with polyester suture in 24
      patients with an average follow up of 8.1 year was presented. The method proved
      to be useful in transverse fractures of the central and distal part od the
      patella as well as in multi-fragmented ones. The evaluation of patello-femoral
      arthritic changes has remarkably influenced the overall clinical result. The
      displacement of 2 mm or more within articular surface existing postoperatively
      implicates bad prognosis, polyester suture is mechanically strong and requires no
      additional operation to remove the material used for fixation.

PMID- 1369898
TI  - [Principles of assessing the treatment of knee instability].
AB  - Multifactorial system of assessment of the results of treatment of the injured
      knee is presented. It comprises of clinical evaluation, modified Lysholm scale,
      set of fitness tests and patient's opinion.

PMID- 1369899
TI  - [Results of treatment for anterolateral knee instability using Ellison's
      operation].
AB  - In 7 patients with anterolateral knee instability Ellison procedure was
      performed. After an average follow up of 56.7 months excellent and good results
      were found in 3 cases using functional assessment scale, in 6 cases according to
      patients opinions and in all cases submitted to fitness tests. The deterioration
      of function in operated knees observed on average 3 years after surgery was due
      to distraction of transplanted structures.

PMID- 1369901
TI  - [Modification of the surgical technique for one stage peri-talar correction of
      congenital clubfoot].
AB  - The surgical technique for one-stage peri-talar correction of congenital clubfoot
      was modified by the author who introduced an accessory lateral approach to the
      tarsus. It enables true elimination of the soft tissue contracture maintaining
      deformity of the foot.

PMID- 1369900
TI  - [Results of suturing peripheral meniscal tears].
AB  - Since numerous complications after meniscectomy, in cases of peripheral tear of
      the meniscus an average follow up of 32.2 months after meniscal suture was
      presented. Excellent and good results in 90 percent of cases reviewed prove this
      procedure to be efficient.

PMID- 1369902
TI  - [Technique of surgical treatment for congenital clubfoot using complete subtalar
      release by the Cincinnati approach].
AB  - The technique of congenital clubfoot surgical treatment based on independently
      described method by Mc Kay and Simons is delineated. We have modified skin
      incision making it ca 2 cm above the calcanean tuber in order to facilitate an
      access for elongation of the calcaneal tendon. In some cases the procedure was
      supplemented with cuneonavicular and first tarsal-metatarsal capsulotomy and
      tibialis anterior muscle tendon transfer to the dorsum of the first metatarsal
      bone.

PMID- 1369903
TI  - [Coexistent paralytic drop foot and gluteal fibrosis after intramuscular
      infections--therapeutic implications].
AB  - Six children with paralytic drop foot, which developed after intramuscular
      injections and who had co-existing gluteal fibrosis are presented in this study.
      Paralytic drop foot was diagnosed on an average of 5.5 months after intra-gluteal
      injections. This was the major therapeutic problem. The diagnosis of gluteal
      fibrosis was made on an average only 3 years and 7 months later. In 3 cases the
      external rotation and abduction contracture of the extremity in the hip joint,
      caused by gluteal fibrosis, with active plantar flexors and supinators of the
      foot could contribute to the recurrence of the equinovarus deformity of the
      surgically corrected foot.

PMID- 1369904
TI  - [Morphological evaluation of fascia lata tissue implantation for chondral defects
      in the knee joint of sheep under active motion and load].
AB  - Experiments carried out on 64 knees of 32 Lein sheep with superficial and deep
      chondral defects of the patella and femoral condyles covered by autogenic fascia
      lata grafts indicate that under active motion and load the grafted tissue after 6
      weeks is thinner, fragile and lustreless. Quantitative and qualitative
      deterioration of collagen fibers, almost complete atrophy of elastic fibers and
      increase in number of cells and vessels is observed under microscope. After 9
      weeks remodeling of the fascia occurs which thickens and increases in number of
      fascicular collagen fibres, after 12 weeks the foci of neochondrogenesis can be
      found. After 26 weeks a new hyaline like cartilage is generated surrounded by
      connective tissue containing fascicular collagen and elastic fibers. At this
      point remodeling is not yet completed.

PMID- 1369905
TI  - [Densitometric bone mineral analysis in the radial metaphysis and its use in
      assessing fluoride changes].
AB  - Theoretical foundations and practical application of densitometric bone mineral
      analysis is presented. The radiographs of forearm and aluminum wedge were
      compared. Bone mineral content (BMC) was calculated on the basis of densitometric
      measurements as well as bone and soft tissue thickness evaluation. The method
      error determined on the basis of tests is 4.89%. The measurements were taken in
      754 fluoride exposed workers and in the control group of 60. A distinctive
      decrease of BMC with age was found in both groups. In older fluoride exposed
      workers this process was slowed down. Minor increase of BMC was found in workers
      exposed to fluoride to the higher degree.

PMID- 1369906
TI  - [Intraoperative diagnostic isotopic bone scanning].
AB  - Advantages of intraoperative bone scintigraphy are presented on the basis of
      surgical treatment of 50 osteomyelitis patients. Tc99m was given either
      intravenously or into the fistula and the radiation was measured by a set of
      scintillating probe and radiometer. Small size, simple handling and quick
      measurement make this set extremely useful for intraoperative diagnostics
      contributing to complete removal of infected tissue from the operating site. This
      method requires only one tenth of usual dose of radioisotope what must be
      recognized as an additional advantage.

PMID- 1369907
TI  - [Long term treatment results of open malleolar fractures].
AB  - Twenty four cases of open malleolar fractures with minimal follow up of 8 years
      after surgery were reviewed. Neglecting to repair ligament injury and in 2 cases
      infection gave bad results of treatment in 6 cases.

PMID- 1369908
TI  - [Correction stabilizing unit for closed reduction of calf bones before their
      union with external fixators].
AB  - The author presents construction and function principles of the correction
      stabilizing unit serving as a device reducing fractured tibial bone before its
      fixation. This unit ensures as well the stability of bone fragments throughout
      surgical fixation.

PMID- 1369909
TI  - [Fracture of the acetabular cup as an early complication of total hip
      replacement].
AB  - The authors have presented 12 patients with non traumatic fracture of the
      acetabular cup of the Weller hip prosthesis. All the fractures have occurred 10
      to 40 months following hip arthroplasty 9 of the broken sockets have been removed
      at the time of revision arthroplasty. They showed marked destruction with
      multiple fragmentation of the polethylen. The area of the destruction was
      surrounded by active tissue reaction described as resorbtion granulation. The
      remowed fragments of the polethylen have been examined physicochemically and
      showed marked increase in the degree of crystalisation. The authors have come to
      the conclusion that the main reason for the failure of the presented series of
      the polietylene cups was defect of the material used in their production.

PMID- 1369910
TI  - [Long term treatment results for acute hematogenous osteomyelitis of the radius].
AB  - The 37 years follow up of hematogenous osteomyelitis of the radius with the whole
      shaft sequestrum is presented. The treatment consisted of surgical removal of the
      sequestrum and administration of both local and systemic antibiotics. One year
      after surgery and subsiding of the flare the fragments were united with an
      autogenic bone graft. After trauma related fracture the incorporated graft has
      united in usual period of time. Clinical and radiological examination carried out
      after 37 years revealed full remodeling of the shaft with features of growth
      disturbances of the radius.

PMID- 1369911
TI  - [Orthopedic terminology of the forearm and elbow].

PMID- 1369912
TI  - [Prof. dr med. Alfons Senger. Obituary notice].

PMID- 1369913
TI  - [Surgical treatment of neglected trauma related dislocations of the cervical
      vertebrae].
AB  - The series of 67 patients operated on for inveterate (more than 3 weeks since
      injury) trauma related dislocation of the cervical vertebrae between 1979 and
      1990 is presented. Up to 3 months after injury an attempt to reduce the
      dislocation by means of the cranial traction has been undertaken. In cases of
      failure surgical reduction of the dislocation was performed. If this was
      unsuccessful in some cases the vertebral body narrowing spinal canal was removed.
      In 60% patients presenting neurological deficits a remarkable improvement was --
      achieved what proves the surgical treatment to be useful even several months
      after injury.

PMID- 1369914
TI  - [The superior vena cava syndrome as an oncological emergency].

PMID- 1369915
TI  - [A proposal for new values in significant bacteriuria].

PMID- 1369916
TI  - [Late results of surgical treatment of infantile idiopathic scoliosis by
      Harrington's method].
AB  - The late results of surgical treatment of infantile scoliosis by the Harrington
      method have been presented in 43 patients. The patients age at surgical treatment
      ranged from 11 to 21 years (14.1 years in the average). The patients age at final
      follow up examination ranged from 18 to 34 years (25.4 years on the average). The
      curvature angle at operation was 102.1 degrees according to Cobb on the average.
      43.7 per cent of curvature was corrected. Although an improvement of posture was
      present in all the patients, only 51 per cent of the patients, had good posture.
      After the treatment 81 per cent of the patients worked.

PMID- 1369917
TI  - [Remarks on treatment of unstable fractures of the thoracolumbar spine].
AB  - An evaluation of treatment results of unstable spine fractures using the
      Harrington instruments in 37 patients has been performed. The described method
      can result in anatomical restoration of the vertebral canal. If vertebral canal
      lumen is not restored, anterior decompression should be performed making possible
      removal of posteriorly dislocated bone fragments. The earlier anterior
      decompression, the greater chance of improvement of neurological conditions. The
      described procedure is especially useful in fractures with partial palsy. After
      treatment 70 per cent of the patients with partial palsy resumed their normal
      lives.

PMID- 1369918
TI  - [Attempts at hierarchic classification of radio-morphologic changes of the lumbar
      spine in screening examinations].
AB  - An objective evaluation of condition of the spine in candidates for study and
      employment in continuous and excessive loading of the lumbar spine is difficult
      because of the lack of suitable criteria classifying pathomorphological changes
      found on X-ray examination. In order to fill this gap, the authors analyzed 85 X
      ray pictures of the lumbar spine of candidates within the preliminary screening
      examinations. A 5-points-scale considering the clinical value of individual
      deviations in lumbar spine structure was accepted. On the basis of that research
      the groups of the examined were determined: able to physical work (0-3 points),
      admitted on condition (4 points) and disqualified (5 points and over). On the
      basis of this model 57.6 per cent of the candidates were disqualified and only
      25.9 per cent were admitted to study and work with no conditions.

PMID- 1369919
TI  - [Spinal fracture in the course of spondylarthritis ankylopoietica (Bechterew
      disease)].
AB  - In 1965-1986 fifty-six patients were treated for fracture of the spine in the
      course of spondyloarthritis ankylopoetica. In 47 patients the cervical spine was
      injured. In 53 patients concomitant neurological symptoms were observed. Total or
      partial palsy were dominant in injuries of the cervical spine (72 per cent). A
      marked neurological improvement was achieved in the course of treatment in most
      of the patients. The authors recommend non-surgical treatment.

PMID- 1369920
TI  - [Current state of knowledge about the application of cryotherapy for treatment of
      musculoskeletal diseases].
AB  - On the basis of literature data and his own investigations, the author discusses
      differential reactions of the human organism to cooling, the varieties of
      cryotherapeutic procedures, their therapeutic efficacy and current views on their
      mechanisms of action, and contraindications to their application. The present
      data indicate that the reflexotherapeutic mechanism plays a fundamental role in
      the analgetic action of cryotherapeutic procedures. The transient
      antiinflammatory influence of a single cryotherapeutic procedure does not undergo
      any additive effect during repetitive application of cooling. Regarding the
      facilitation of the kinesitherapy, cryotherapy appears a valuable means in the
      symptomatic management of inflammatory and noninflammatory diseases of the
      locomotor system.

PMID- 1369921
TI  - [Surgical treatment of residual congenital dysplasia with dislocation of the hip
      joint after treatment with the Frejka pillow].
AB  - The characteristics of patients and the radiological condition of hip joints that
      required surgery because of residual dysplasia in the course of growth after
      treatment by the Frejka pillow have been presented. That treatment was employed
      in 4 per cent of the treated hips. The operations consisted in inspection of the
      joint, transiliac osteotomy after Dega with subtrochanteric osteotomy with
      detorsion of the femur, of the same type of operation without opening of the
      joint, performance of only transiliac osteotomy or only subtrochanteric
      osteotomy. Because late evaluation at over 10 years of life revealed 5 per cent
      of hips with poor rebuilding that should be treated surgically, it has been
      determined that the total number of cases requiring surgery after treatment by
      the Frejka pillow is 9 per cent.

PMID- 1369922
TI  - [Aseptic necrosis of ischiopubic synchondrosis (osteochondrosis ischiopubica) as
      the cause of diagnostic difficulties in pathology if the infantile hip].
AB  - Two cases of aseptic osteochondrosis ischiopubica in a 6-years-old girl and a 10
      years-old boy have been presented. In the described cases the radiological and
      clinical picture was the reason of diagnostic difficulties suggesting diagnosis
      of tumor and hematogenic osteitis.

PMID- 1369923
TI  - [Early results of leg bone lengthening using epiphysis-metaphysis distraction].
AB  - The methods and results of elongation of the lower extremity by epiphysis
      metaphysis distraction obtained at treatment of 13 children aged from 4 to 15
      years, with abbreviation of 30-80 mm have been presented. In 11 children full
      elongation of the abbreviation of 30-57 mm was obtained. In two children full
      elongation was not obtained.

PMID- 1369924
TI  - [Injury of the acromial end of the clavicle imitating dislocation of the acromio
      clavicular joint].
AB  - Two patients have been presented: a 15-years-old boy with rupture of the
      clavicular-coracoid ligaments as in total acromioclavicular dislocation, in whom
      dislocation of that joint did not occur but acromial epiphysiolysis of the
      clavicle (this patient, was successfully treated surgically) and 5-years-old boy
      with strain of the clavicular-coracoid ligaments and fracture of the acromial end
      of the clavicle; he was treated conservatively with remaining of angular
      dislocation of the distal fragment. The hope for rebuilding of the axis was
      fulfilled in that child. The anatomical and functional result in both patients is
      good.

PMID- 1369925
TI  - [A self-constructed device for reduction and stabilization of multi-fragmented
      fractures of the patella. Technical data and analysis of clinical material].
AB  - The author has presented the construction and use of his own device for reduction
      and stabilisation of multi-fragment fractures of the patella ("patella-clamp").
      The device was examined in action first on cadavers and then introduced to
      clinical use. The use of the "patella-clamp" made possible to obtain better
      results in surgical treatment of multi-fragment fractures of the patella.

PMID- 1369927
TI  - [Free cutaneous-muscle flap from the latissimus dorsi muscle].
AB  - Free cutaneous--muscular flap from the latissimus dorsi muscle was used to cover
      extensive posttraumatic skin defect of the distal tibia in a patient with lesion
      of the anterior tibial artery. The technique of flap transfer and vascular
      anastomosis has been presented. Full healing was achieved.

PMID- 1369926
TI  - [Examination the extent of flap rotation from the medial head of the
      gastrocnemius muscle].
AB  - The authors evaluated various methods of range lengthening of muscular and
      cutaneous--muscular flaps from the medial head of the gastrocnemius muscle on 18
      amputated lower extremities and section specimens. It has been found that
      lengthening of flaps size by Cheng and transformation of the muscular and
      cutaneous--muscular flap into the island flap produced marked lengthening of flap
      arch. The authors believe that incisions of the perimysium can not be recommended
      as a method of lengthening of flaps range.

PMID- 1369929
TI  - [Disorders of lipid metabolism in aseptic necrosis of the femoral head in
      adults].
AB  - 14 cases of aseptic necrosis of the femoral head, in which disorders of lipid
      metabolism were found, have been presented. Literature on aseptic necrosis
      qualities lipid disorders as agents of risk. In the presented cases, lipid
      disorders have indicated occurrence of the IV type of hyperlipoproteinemia
      according to Fredrickson.

PMID- 1369928
TI  - [Arthrodesis of the hip joint as a treatment of degenerative changes--anachronism
      or an alternative for endoprosthetic arthroplasty?].
AB  - On the basis of the observation of 22 patients with arthrodesis of the hip (the
      average age -- 34 years), the value of the method in the treatment of
      osteoarthritis that joint has been discussed. The comparison of intraarticular
      arthrodesis with stable compression with pelvis osteotomy and stabilization by
      the "cobra" plate has proved that the second method is better because of
      elimination of immobilization by a plaster cast and low percentage of
      complications of union. The clinical analysis of the majority of the patients has
      not revealed negative influence of arthrodesis on the other hip, the lumbar spine
      and the knee. Arthrodesis of the hip has improved walking efficiency and ability
      to work in 17 from 22 patients. Very good and good results have been obtained in
      16 patients, fair in 3, and poor in 3.

PMID- 1369930
TI  - [Clinical evaluation of the usefulness of knee arthroscopy].
AB  - The authors have analyzed the results of 570 cases of knee arthroscopy performed
      in 1974-1987, which included 441 diagnostic and 129 operative arthroscopies. The
      greatest diagnostic group consisted from 163 cases of suspicion of meniscus
      injury. Chondromalacia of the patella was the reason for arthroscopy in 53 cases.
      The importance of joint clinical and arthroscopic examination has been stressed.

PMID- 1369931
TI  - [Radiologic examination for diagnosis of intraarticular knee injuries].
AB  - A set of 4 projections of radiological examination performed on patients with
      intraarticular injuries of the knee has been presented, namely: 1) the a-p view
      of the knee in the standing position, 2) the 1-1 view with 30 degrees of flexion
      in the lying position, 3) the axial view of patellae, 30 degrees of flexion of
      the knee, standing position, 4) the tunnel view of the knee joint. The
      significant role of radiological examination, beside clinical examination and
      arthroscopy in diagnosis of these injuries has been stressed. Clinical practice
      has proved great usefulness of the performed projections.

PMID- 1369932
TI  - [Results of treating recurrent dislocation of the patella by the Garlick-Salamon
      method].
AB  - The Garlicki-Salamon method consists in isolation of the patella ligaments,
      loosening of the lateral pulleys, medial and downward transposition of the
      patella ligament insertion, wrapping of the medial joint capsule, and transfer of
      the m. vastus medialis insertion to the medial-upper quadrant of the patella. The
      late follow-up (at least 5 years of observation) was carried on in 26 knees. 4
      results were excellent, 10 -- good, 8 -- fair, 4 -- poor. In nine cases (35 per
      cent) development osteoarthritis of the patello-femoral joint was found.
      Recurrence of dislocation was found in 4 cases.

PMID- 1369933
TI  - [The possibility of using carbon material in surgery of joints].
AB  - The experiments consisting in replacement of a dissected anterior cruciate
      ligament of the knee in rabbits with a bundle of parallel carbon fibers and a
      braided carbon covered with animal collagen lyophilized dura mater have been
      performed. Similar experiments have been performed on dogs. The lateral ligaments
      of the knee were also restored, longitudinally cut menisci and the Achilles
      tendon were sutured. The produced carbon plate and metal screws were used to fix
      bone fracture. The positive results of the experiments on animals with the use of
      carbon fibers of Polish make have proved the possibility of their employment for
      periarticular ligament reconstruction, suturing, Achilles tendon injuries and
      juxta capsular meniscus rupture. The union of bone fracture with a composite
      carbon plate has shown the superiority of "carbon" osteosynthesis over "metal"
      one. It is believed that carbon materials will be used clinically more widely.

PMID- 1369934
TI  - [Osteitis and reconstruction of shaft defects of long bones].
AB  - The results of treatment of 18 patients with post-inflammatory shaft defects of
      the long bones within the femur, the tibia, and the humerus have been presented.
      The defect ranged from 2 to 4 cm in most of the cases; it was 8 cm in one case,
      10 cm in two cases and over 20 cm in two cases. The treatment method consisted in
      active, multidirectional surgical procedure overcoming the inflammatory process
      and changing the "infected" case into a "clean" one making possible to use the
      generally accepted treatment methods. Healing of grafts and bone union was
      obtained in all 18 cases, marked restriction of movement in the knee joint was
      found in 4 patients, and recurrence of the inflammatory process of mild clinical
      course was found in 4 cases.

PMID- 1369935
TI  - ["Taurolin-Gel" and Taurolin-Trockengel" in treatment of osseous tissue
      inflammation].
AB  - The activity and principles of administration of Taurolin have been presented.
      That drug was used in 15 patients with chronic osteitis. Healing by first
      intention was obtained in 10 patients, necrosis of the skin occurred in 3
      patients, recurrence of inflammation was found in one patient in whom accessory
      sequestroctomy was performed in the last case of osteitis and arteriosclerosis
      healing was obtained by second intention. The clinical observation of 15 patients
      has revealed: a) irritating influence of Taurolin on the soft tissue, b)
      increased phase of secretion of exudate since the 5 day after surgery, c)
      bactericidal influence of the drug. Sterilization of the focus occurred at 2 to 3
      weeks after surgery. The use of Taurolin requires experience, complete abiding by
      the principles of use of this drug and equipment with a set of Charrier's drains.
      The authors are carrying on further observation of the use of Taurolin in the
      treatment of osteitis.

PMID- 1369936
TI  - [A remark on diagnosis of osteogenic sarcoma in a rare location].
AB  - Two cases of osteogenic sarcoma localized in the femoral neck have been
      presented. As it has resulted from literature, such a localization is very rare
      and it matches great diagnostic difficulties, mainly caused by absence of typical
      periarticular reactions and ambiguous X-ray pictures. Angiography and
      computerized tomography are helpful in diagnosis of the type of tumor.
      Histopathological examination is decisive.

PMID- 1369937
TI  - [Composite antebrachial island flap].
AB  - Two cases of antebrachial island flap including the radial bone have been
      presented. In the first patient it was used to fill infected defect of skin and
      the 2nd metacarpal bone. In the second patient, the operation was indicated by
      shortening (2 cm) of the 3rd metacarpal bone after its intraarticular fracture.
      In both patients, the bone and skin grafts healed.

PMID- 1369938
TI  - [A telescopic device for stabilization-distraction].

PMID- 1369939
TI  - [The 60-year jubilee of Prof. Dr Hab. Med. Witold Szulc].

PMID- 1369940
TI  - [The 35th anniversary of the Cathedral and clinica of Orthopedics in Lublin].

PMID- 1369941
TI  - [Origin and development of the children's orthopedic clinic].

PMID- 1369942
TI  - [Activities of the podiatric group in the Lublin orthopedic departments under the
      direction of Professor Stanislaw Piatkowski].
AB  - The development of podology in the Lublin society as well as the personal
      achievements of prof. Stanislaw Piatkowski have been presented. The originated in
      the 60-ies activities concerning podology have included scientific research,
      cooperation with shoe industry institutions, and wide prevention of the foot
      health in the Lublin region.

PMID- 1369943
TI  - [Radiologic and clinical evaluation of the wrist in some movement disorders of
      children].
AB  - The wrist angle in X-ray pictures of the hand in 47 children, aged 6-16 years,
      treated for bone growth disorders, was evaluated. The obtained results were
      compared with the wrist angle in normal children. The increase of the wrist angle
      was observed in deformations: dwarfism, gargoylism and dysplasia multiplex, and
      the decrease of this angle in the Turner syndrome. The range of passive and
      active movements of the wrist was evaluated. Passive and active mobility of the
      wrist (especially the radial and the ulnar deviations) was smaller in the cases
      of increased wrist angle.

PMID- 1369944
TI  - [Surgical treatment of Smith and Barton type fractures].
AB  - The method and the results of surgical treatment of Smith and Barton fracture of
      the distal radial epiphysis has been presented in 10 patients. Dislocation of
      fragments is reduced after exposure of the palmar side of the distal radial bone.
      Stabilization is secured by a metal plate, which supports the epiphysis and is
      fixed to the proximal fragment by screws. It prevents from redislocation of
      fragments and helps to recover full activity of the hand, which was obtained in 8
      patients. Delayed reduction or stabilization of fragments by Kirschner wires in 2
      persons has failed.

PMID- 1369945
TI  - [Specific character of movement disorders in children studying string
      instruments].
AB  - Orthopaedic examinations were carried out in 242 children studying string
      instruments. Various indispositions and deformations of the motor organs were
      found in 31 children. It has been demonstrated that they were mainly the result
      of technical errors in holding of the instrument, which caused overloading of the
      upper extremities and the spine.

PMID- 1369946
TI  - [The role of static-dynamic factors in genesis of femoral head and neck
      deformation in dysplastic hips. A physical-mathematical interpretation ].
AB  - The clinical material for a physical-mathematical analysis of femoral head and
      neck deformations in subluxated and luxated hips consisted of 1.574 case
      histories of children operated on in 1954-1988. In that material 21.9 per cent of
      the children had preoperative growth disorders of the head, and in the half of
      the cases also the femoral neck was involved. In 10.79 per cent of the children
      pre- and postoperative trophic disorders were also observed. On the basis of the
      physical-mathematical analysis of static-dynamic factors of the hip, it has been
      determined that the disordered shape of the femoral head and neck is most of all
      the result of defective formation of the roof. The oblique roof changes the
      static and dynamic forces acting on the femoral head and neck in such a way that
      large overloading of the growth zones of the medial side occurs and is followed
      by development of proximal femur deformation.

PMID- 1369947
TI  - [The protease-antiprotease system in pathogenesis of transient arthritis of a
      single joint in children].
AB  - In 35 patients with transient arthritis of a single joint, levels of alpha-1
      antitrypsin were determined in the serum in the acute stage of the disease, the
      recovery period, and the control group. The results were compared. Determination
      was that the results of examination have indicated a markedly increased level of
      carried out by the use of M-Partigen, immunodiffusive plates by the Mancini me
      alpha-1-antitrypsin in the serum in children in the acute period of this disease
      and a significant decrease of its level in the period of subsidence of the
      clinical symptoms in comparison with the control group. The changes in the level
      of this enzyme indicate disturbance of protease-antiprotease balance in
      pathogenesis of this disease.

PMID- 1369948
TI  - [Ultrasonography in transient hip synovitis in children].
AB  - Ultrasonography was performed in 10 children with the symptoms of transient hip
      synovitis. In all the patients inflation of the capsule was found. At the
      following examinations subsidence of intraarticular exudate was observed.

PMID- 1369949
TI  - [The influence of geometry of the total hip endoprosthesis on late functional
      results].
AB  - The influence of some parameters of incorrect position of elements of an
      endoprosthesis of the hip on the late functional result of 61 endoprosthetic
      arthroplasties have been analyzed. The authors believe that the group of several
      factors of incorrect mounting of elements of an endoprosthesis is usually the
      cause of deterioration of treatment results due to occurrence of clinical and
      radiological symptoms of loosening of the endoprosthesis.

PMID- 1369950
TI  - [Functional result and telemetric evaluation of gait after total endoprosthetic
      arthroplasty of the hip].
AB  - The late functional results of one-side endoprosthetic arthroplasty in 35
      patients, supplemented with telemetric examination of temporal parameters of
      gait, have been presented. The marked correlation of the obtained results of
      telemetric examination with clinical and radiological state of the operated on
      hip has been found. The authors stress the favorable and rational effect of the
      cane in unloading of the inefficient lower extremity.

PMID- 1369951
TI  - [Partial patellectomy in treatment of fresh fractures of the patella].
AB  - The late results of partial patellectomy in treatment of fracture of the apex or
      the 1/3 of the peripheral patella have been presented. Fourteen patients were
      evaluated. Attention was paid to the dependence of the result on the correct
      surgical technique. Full painless range of movements in the operated on knee was
      achieved in 7 persons. In the other 7 patients, extension of the knee was full
      but flexion was moderately limited. Periodical pain occurs in 3 persons.

PMID- 1369952
TI  - [Resection of the patella and plasty of the knee by the de la Caffiniere method].
AB  - The surgical technique of patellectomy with preservation of continuity of the
      extension apparatus of the knee by the de la Caffiniere method and the early
      results of treatment in 8 operated on patients have been presented. The
      indications for surgery were: posttraumatic stiffness of the knee in extension in
      4 patients, patello-femoral arthrosis with preserved wide range of movement in 3
      patients, fresh multi-fragmented fracture of the patella without rupture of the
      extension apparatus in one patient. The good treatment result was obtained in 6
      patients (3 treated for patello-femoral arthrosis, 1 for fresh fracture of the
      patella, and 2 for stiffness of the knee in extension). The poor results in the
      other 2 patients operated on or stiffness of the knee in extension were due to
      large damage of the cartilaginous surface of the condyles and extensive intra-
      and periarticular adhesions.

PMID- 1369953
TI  - [Characteristics and diagnosis of neoplastic metastasis to bones].
AB  - On the basis of the analysis of 156 hospitalized patients, the most important
      traits differentiating metastasis of various organs to the bones have been
      presented. It has been found that the bones are most frequently invaded by kidney
      cancer, somewhat less frequently by breast cancer and the bronchus cancer and
      markedly more rarely by cancer of other organs. The types of metastasis expansion
      in the bones were determined radiologically: the most frequent--osteolytic, less
      frequent--mixed, and the osteoplastic type (prostate cancer, gall-bladder cancer,
      and pancreas cancer). Metastasis is situated most often in the spine and the
      femur. The authors have also presented the tactics of diagnosis of metastasis by
      using data from anamnesis, clinical and radiological examination and directed
      specialist examinations, for instance arteriography of the kidneys at suspicion
      of kidney cancer. In spite of complex diagnostics the source of metastasis was
      not found in over a dozen of patients.

PMID- 1369954
TI  - [Outcome of treating solitary osseous cyst with acetate methylprednisolone
      injections].
AB  - Among 24 children with solitary osseous cyst of various localization treated by
      local methyl prednisolone injections, 20 children had excellent and good results.
      The radiological criteria of evaluation were as follows: full rebuilding of the
      bone in the site of cyst--excellent result, irregular trabecular structure or
      widening of the bone remain--good result, small radiological translucency with
      simultaneous full rebuilding of width of the cortical bone, securing proper
      mechanical resistance--fair result, absence of radiological traits of rebuilding-
      poor result. In each patient, 4-6 instillations were performed every 3 months.
      Subsidence of local compression and auscultative pain, deliberation of balloon
      inflation of the metaphysis, normalization of width of the cortical bone,
      rebuilding of the spongy bone and "going away" of the epiphyseal cartilage from
      the cyst have been observed.

PMID- 1369956
TI  - [Axial spondylometer--a device for measurement of the configuration and mobility
      of the spine in three planes].
AB  - A method of triplanar assessment of the configuration and mobility of the spine
      with the use of the original axial spondylometer is described. The device allows
      to present mobility in the plane of two perpendicular axes X and Y in new
      categories: elasticity, susceptibility and deshaping of the spine.

PMID- 1369955
TI  - [History of functional treatment of fractures].
AB  - A concise history of fracture treatment from ancient times to XIX century, when
      the old rules of management started to be modified are presented at the
      beginning. An isometric traction methods of treatment as well as isotonic ones
      both indirect and direct have been discussed. The shortcomings of fraction
      treatment induced application of functional treatment that was a combination of
      the traction and joint movements assisted by the mechanical devices. The author
      indicates that functional treatment methods were not known to polish orthopaedic
      surgeons up to the seventies. This empty space was filled only in the last
      decade. From historical analysis author concludes that external fixation is the
      future of fractures treatment.

PMID- 1369957
TI  - [Spondylometric assessment of the configuration and flexion-extension mobility of
      the spine in students].
AB  - An original method of assessment of the configuration and mobility of the spine
      in the sagittal plane with the use of axial spondylometer allowed reproducible
      and more objective evaluation of the spinal movement then previously employed
      methods. A qualitatively new assessment of the spinal mobility was achieved due
      to the introduction of mathematical indicators of elasticity, susceptibility and
      reshaping of the spine. The evaluation of the spinal range of motion in 167
      students indicated prominent sexual dimorphism. The elasticity and flexion
      reshaping indicators in males exceeded of 17.6% and 21.6% respectively the
      females ones. The circular mobility of the spine greater then its distensibility
      is characteristic for males. In both sexes flexion surpasses extension of the
      spine from 157% to 215%.

PMID- 1369958
TI  - [Trauma related subtalar dislocation of the foot].
AB  - Eight cases of subtalar foot dislocation (5 cases of medial displacement, 2
      lateral and 1 very rare anterior one) has been presented. On the basis of authors
      experience and literature the mechanism and the principles of diagnostics and
      treatment of this injury has been discussed.

PMID- 1369959
TI  - [Early results of surgical treatment for congenital dislocation of the hip by the
      Degi method in young children].
AB  - The early results of surgical treatment of congenital dislocation of the hip by
      complex Dega method in children aged from 18 to 30 months has been presented. The
      reduction of the hip after all the obstacles and the elements of dysplasia has
      been removed was very stable. Derotation osteotomy of the femur in the hips of
      less than 50 degrees anteversion was not necessary. Avascular necrosis after
      surgical treatment alone was not observed, however its presence after previous
      conservative management worsened the results after the operation.

PMID- 1369961
TI  - [A case of sacral agenesis coexisting with Goldenhar syndrome].
AB  - A case of two coexisting embryopathies has been described. The deformities within
      the sacral bone and systemic anomalies led to the diagnosis of sacral agenesis;
      Goldenhar syndrome has been differentiated with other disturbances of branchial
      arches formation.

PMID- 1369960
TI  - [Treatment of the deformities associated with hypoplasia or agenesis of the
      sacral bone].
AB  - On the basis of follow-up of 5 children treated because of the deformities
      associated with sacral agenesis or hypoplasia as well as on the literature the
      authors came to the conclusion that congenital dislocation of the hip, clubfoot
      and flatfoot are the most common. The aim of the treatment is to prepare the
      child for walking before the end of the first year of life. Since the deformities
      mentioned are resistant to conservative treatment they require a very
      sophisticated surgery with the constant adjustment of the operating plan in every
      stage of the management. The type of hip surgery should be selected individually.

PMID- 1369962
TI  - [Chronic rotational dislocation in the lateral atlanto-axial joint in a seven
      year old girl].
AB  - A case of inveterate, rotational dislocation in the atlanto-axial joint type III
      in 7 year old girl hit by a car was presented. Direct skull traction was applied
      resulting in complete reduction and regaining of the full range of motion in the
      cervical spine.

PMID- 1369963
TI  - [Mechanical properties of tissue generated as a result of fascia lata grafted
      into an articular cartilage defect of the knee joint (experimental
      observations)].
AB  - In 64 sheep knees crushing strength and elastic recovery of the tissue generated
      on the basis of fascia lata grafted into articular cartilage defect in the knee
      after active motion and load has been assessed. The newly generated tissue is
      characterized by increasing in time thickness, deformability and elastic recovery
      the greater the deeper the defect was. Primarily, the new tissue is able to carry
      smaller loads but after 26 weeks is capable of carrying much greater loads then
      the cartilage; it has also better plastic and elastic properties.

PMID- 1369964
TI  - [Angiosarcoma of the femur following chronic osteomyelitis].
AB  - Available literature concerning neoplastic metaplasia of the bone undergoing
      chronic osteomyelitis has been cited. The treatment of 62 years old patient with
      lasting 47 years chronic osteomyelitis of the femur after shotgun wound was
      presented in details. The diagnosis of angiosarcoma following chronic
      osteomyelitis has been established histologically. The extremity has been
      amputated with good result--no metastasis or recurrence was found during follow
      up.

PMID- 1369965
TI  - [Mineral changes occurring with age in the intervertebral disks of L4-L5
      vertebrae].
AB  - The results of mineralogical examination of 26 L4-L5 intervertebral discs taken
      from cadavers has been presented. Radiology did not reveal marked osteoarthritic
      changes at this level. The age of the individuals at the fatal accident ranged
      from 4 to 87 years (mean 41.2). -- Scanning microscopy, atom absorbtion
      spectroscopy and roentgen microscopy was used in the examination. Two age related
      phenomena were discovered; demineralisation of the nucleus pulposus and
      mineralisation of the anulus fibrosus. Two types of mineralisation were found;
      the microscopic one visible as granules of different shape and size consisting of
      crystalline hydroxyapatite aggregates and the one detectable exclusively by
      sensitive chemical methods as an increase of Ca and P content and disturbance of
      the remaining elements content in biological structures.

PMID- 1369966
TI  - [Mechanism of articular fracture of the calcaneus in experimental, pathological,
      roentgenographic and computerized tomography examination].
AB  - The experiments on amputated extremities, pathological examination as well as
      plain and computerized radiology confirmed existence of two basic types of
      calcaneal articular fractures: tongue type and crush type. An accurate anatomy of
      the experimentally fractured os calcis could be restored only after Westhues. An
      articular surface in crush fracture could be restored only in open arthrotomy.
      Computerized tomography revealed the type of the fracture and the degree of
      calcaneal destruction very precisely but was of no practical value in the
      treatment of the os calcis fractures.

PMID- 1369967
TI  - [Assessment of the value of stimulation from a preparation of Tolpa peat for
      treatment of trauma related osteomyelitis].
AB  - Tolpa peat preparation at the dose of 5 mg per day was administered to 10
      patients with chronic posttraumatic osteomyelitis for 6 weeks period of time.
      Good clinical result (ceasing of the inflammatory process) was found in 4
      patients but 3 of them were concurrently treated surgically. Immunological
      examination (angiogenesis test and chemiluminescence test) performed before the
      onset and after completion of the treatment with Tolpa preparation did not reveal
      meaningful changes indicating immunomodulating action of the preparation on the
      course of posttraumatic osteomyelitis.

PMID- 1369969
TI  - [Use of Dynasplint in prevention of muscular contractures in limbs undergoing
      lengthening].
AB  - Dynamic splinting with Dynasplint for prevention of muscular contractures and
      subluxations in the joints during lower limb lengthening in 10 children has been
      used. In all cases the splint successfully prevented subluxation in the knee and
      the foot deformity. Ability to move splinted joints allowed effective
      rehabilitation. The splint was well tolerated by all the patients during whole
      period of distraction.

PMID- 1369968
TI  - [Use of the Weber method in treatment of acromioclavicular dislocation].
AB  - The results of treatment of 10 patients with acromioclavicular dislocation has
      been presented. In all cases acromioclavicular fixation was done with Weber
      tension band (Zuggurtung). Additional immobilisation was not used so an early
      rehabilitation was possible. Full range of motion of the shoulder joint was found
      in 9 patients.

PMID- 1369970
TI  - [Use of magnetotherapy for treatment of bone malunion in limb lengthening.
      Preliminary report].
AB  - Two children with bone malunion after lengthening of congenitally shortened lower
      leg have been presented. The crus has been elongation 8 cm by Ilizarov method in
      9 years old boy and 5 cm elongation of the tibia has been achieved with the use
      of Bastiani method in 8 years old girl. In both cases malunion has occurred. The
      radiographs revealed pseudoarthrosis (the girl, 6 month after operation) and
      centrally located bony defect (the boy, 2 months postoperatively). In both cases
      pulse sinusoidal magnetic field was applied successfully with cortical bone and
      marrow cavity restored in 2 months.

PMID- 1369971
TI  - [The value of ultrasonography in monitoring limb lengthening].
AB  - The authors attempted to assess the value of ultrasound for monitoring of the new
      bone formation at the site of distraction in patients undergoing limb lengthening
      after Bastiani. Twenty patients were assessed; 12 cases of femur lengthening and
      8 cases of tibia lengthening. It was found, that ultrasound allowed to detect the
      new bone formation visible as hyperechogenic foci as soon as 4 to 14 days
      postoperatively, while regular radiology showed this only 4 to 8 weeks after
      operation. Detection of the new bone formation at the site of lengthening
      permits, in authors opinion, to choose an optimal onset of distraction and its
      pace according to the speed of bone formation. Regular ultrasound monitoring
      prevents premature bone union or disintegration of the newly generated bone in
      case of to slow or to fast distraction respectively. In two cases sonography
      early demonstrated cystic changes at the location of distraction. It also permits
      detection of an axial displacement of the fragments of bone in every case.

PMID- 1369972
TI  - [Universal hip fixator "Zespol". Construction of the fixator, principles of
      function, instrumentation, surgical technique, indications and results of
      treatment].
AB  - The construction and principles of function of hip fixator based on Zespol
      method, with compression of the fragments provided by elastic deformation of a
      plate is presented. Original instrumentation, operative technique and indications
      for this type of osteosynthesis is described. Results analysis revealed that out
      of 64 patients 10 died within 6 month from surgery, all of them older than 80
      years of age. In 46 from remaining 56 patients a union of fractured bone was
      found. There were 82.2% of good results in patients with femoral neck fracture
      and 87.5% in the group with trochanteric fractures. Few complications produces
      hope for Zespol hip fixator to become valuable device for treatment both
      trochanteric and femoral neck fractures.

PMID- 1369974
TI  - [The thinking man].

PMID- 1369973
TI  - [Orthopedic terminology of the arm and shoulder].

PMID- 1369975
TI  - Effect of luminal acidification on guinea pig gastric mucosa.
AB  - H+ secretion was studied in guinea pig fundic mucosa incubated in (A) bicarbonate
      Ringer's gassed with 95% O2-5% CO2, or (B) HEPES gassed with 100% O2 before and
      after luminal pH was lowered to 2.0 for periods up to 90 min. At pH 2.0 for 60
      min, H+ secretion in group A tissues fell by 35 +/- 4% (P = 0.02) from a control
      rate of 1.35 +/- 0.09 mu eq/cm2/hr and in group B tissues by 50 +/- 11% (P =
      0.01) from a control rate of 1.59 +/- 0.08 mu eq/cm2/hr. After 90 min at pH 2.0,
      H+ secretion in group A fell by 53 +/- 8% (P = 0.02) from a control rate of 1.47
      +/- 0.07 mu eq/cm2/hr and in group B fell by 44 +/- 6% (P = 0.01) from a control
      rate of 1.38 +/- 0.07 mu eq/cm2/hr. Histamine 1 x 10(-4) M stimulation following
      exposure to pH 2.0 for 90 min increased secretion in group A tissues from 0.80 +/
      0.14 to 1.06 +/- 0.13 mu eq/cm2/hr (P < 0.05), compared with an increase in
      nonacidified controls from 1.15 +/- 0.22 to 1.80 +/- 0.20 mu eq/cm2/hr (P < 0.05)
      and in group B tissues from 1.27 +/- 0.10 to 1.56 +/- 0.19 mu eq/cm2/hr (P <
      0.05) compared with nonacidified controls from 1.43 +/- 0.22 to 2.23 +/- 0.41 mu
      eq/cm2/hr (P < 0.05). Secretory function and electrical characteristics were
      adversely affected by luminal acidification to pH 2.0 and suggested a breach in
      the mucosal barrier with damage to parietal cells.

PMID- 1369976
TI  - [Is the use of antipyretics justified in lowering fever and preventing febrile
      convulsions in children?].

PMID- 1369977
TI  - L-lysine repression of penicillin biosynthesis and the expression of penicillin
      biosynthesis genes acvA and ipnA in Aspergillus nidulans.
AB  - The addition of 0.1 M L-lysine to the fermentation medium reduced the production
      of penicillin by about 50% in Aspergillus nidulans. To analyse this effect at the
      molecular level, the expression of the penicillin biosynthesis genes acvA and
      ipnA, encoding delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase and
      isopenicillin N synthetase, was studied by using translational fusions with
      different reporter genes (strain AXB4A, acvA-uidA, ipnA-lacZ fusions; AXB4B, acvA
      lacZ, ipnA-uidA fusions) integrated in single copy at the chromosomal argB locus
      of Aspergillus nidulans. Irrespective of the reporter genes used the expression
      of acvA and ipnA fusion genes was repressed in L-lysine grown cultures. The
      expression of a fusion gene of an A. nidulans primary metabolism gene (oliC-lacZ)
      was not affected by L-lysine.

PMID- 1369978
TI  - Use of a modified cupric acetate method for the detection and quantitation of
      xylanolytic activities: a comparative study with the congo red method.
AB  - A modified cupric acetate method for the screening and quantitation of
      xylanolytic activities was comparable with the more widely used congo red method
      with respect to sensitivity and ease of use and was shown to have points of merit
      over the latter. The use of a non-linear correction, in comparison to the
      conventional linear one, for the effect of dilution on the quantitative plate
      assay was evaluated.

PMID- 1369979
TI  - High resolution dynamic imaging: a method for direct monitoring of gel
      electrophoresis.

PMID- 1369980
TI  - A general method to generate DNA probes for microorganisms.
AB  - We present a method that permits the rapid generation of DNA probes for
      eubacteria. In the procedure the variable regions for the 16s rRNA genes are
      amplified using polymerase chain reaction (PCR) technology and primers based on
      the conserved regions of these genes. Following sequencing of the variable
      regions, a choice is possible for a probe specific for that organism. No
      knowledge of the molecular biology of the microorganism is required prior to the
      application of this approach. The generality of the method is shown using
      Salmonella typhimurium, Staphylococcus aureus, Clostridium perfringens,
      Klebsiella pneumoniae, Pseudomonas fluorescens, Aeromonas salmonicida and
      Mycobacterium bovis. A. salmonicida was examined in detail and a DNA probe was
      prepared that distinguishes it from other Aeromonas species.

PMID- 1369982
TI  - Synthesis and characterization of soluble dextran-adenosine phosphate complexes:
      kinetic effects of coenzyme loading.
AB  - Soluble dextran-ATP complexes have been synthesized using a bifunctional oxirane
      as the coupling agent. The degree of coupling is time-dependent, allowing
      materials of varying coenzyme loadings to be produced very simply.
      Characterization studies have shown that at the maximum coenzyme loading obtained
      (34 molecules per complex) all coenzyme moieties were coenzymically active with
      hexokinase. The extent of coenzyme loading was shown to have a considerable
      influence on the values of Km and Vmax of the complex as a substrate for
      hexokinase. Enzyme activity was also found with acetate kinase and myokinase, and
      coenzyme recycling (ATP, ADP) was demonstrated in an ultrafiltration reactor.

PMID- 1369981
TI  - Fat-body-specific expression of the Drosophila Lsp-2 gene.
AB  - The larval serum protein-2 gene (Lsp-2) of Drosophila melanogaster is expressed
      at a very high level in the fat body of third-instar larvae. Here we report that
      Lsp-2 transcription in adult flies produces a unique mRNA localized in the adult
      adipose tissue of the head in both sexes. To identify regulatory regions of this
      Drosophila gene, Lsp-2 5'-flanking DNA sequences were fused to the E. coli beta
      galactosidase gene (lacZ). Transient expression of the hybrid gene in third
      instar larvae indicates that 230 bp just upstream from the 'TATA box' of the Lsp
      2 gene are sufficient for larval fat body-specific expression.

PMID- 1369983
TI  - Discrimination of fetal bovine serum from other sera by silver staining or lectin
      blotting of SDS/PAGE-separated serum proteins.
AB  - In order to develop a methodology to discriminate fetal bovine serum from other
      sera with which it might be contaminated, proteins from fetal bovine, newborn
      calf, colostrum-free newborn, and calf sera were separated by SDS/PAGE and
      analyzed by silver staining of the gels or lectin blotting, using concanavalin A
      (Con A), following transfer of the proteins to nitrocellulose. A high molecular
      weight Con A-reactive glycoprotein of an apparent molecular mass greater than
      200,000 daltons was present in newborn, colostrum-free, and calf sera, but absent
      or at a significantly lower concentration in fetal serum. These two methods
      accurately and reliably identified contamination of fetal serum with other sera
      in a series of blind studies on unknown, coded samples. As little as 1% colostrum
      free serum in a batch of fetal serum can be detected by either procedure.

PMID- 1369984
TI  - Functional protein-polysaccharide conjugate prepared by controlled dry-heating of
      ovalbumin-dextran mixtures.
AB  - A functional ovalbumin-dextran conjugate was prepared by dry-heated storage at 60
      degrees C and 65% relative humidity for 3 weeks. The emulsifying properties of
      the ovalbumin-dextran conjugate were about three times higher than those of an
      ovalbumin-glucose conjugate. SDS-electrophoresis patterns showed that the
      ovalbumin-dextran conjugate obtained by dry-heating was not as polydispersed as
      that obtained by cyanogen bromide-activated dextran. The average molecular weight
      of the ovalbumin-dextran conjugate was about 200,000. The excellent emulsifying
      properties of ovalbumin-dextran conjugate were maintained even at pH 3 and were
      further improved at pH 10. In addition, the emulsifying properties of the
      ovalbumin-dextran conjugate were greatly enhanced by preheating the conjugate at
      100 degrees C. Thus, it is suggested that an ovalbumin-dextran conjugate prepared
      by controlled dry-heating can be used as a macromolecular emulsifier for food
      applications.

PMID- 1369985
TI  - Induction and efficient purification of endo-alpha-N-acetylgalactosaminidase from
      Alcaligenes sp.

PMID- 1369986
TI  - Comparison between the antigenicity of native and unfolded beta-lactoglobulin.
AB  - The antibody binding sites (B-cell epitopes) on beta-lactoglobulin (beta-LG) were
      surveyed by assaying the reactivity of the tryptic fragments of beta-LG to mouse
      anti-beta-LG antiserum with ELISA. Four peptide fragments (the residues 21Ser
      40Arg, 41Val-60Lys, 102Tyr-124 Arg, and 149Leu-162Ile) bound the antibodies. We
      considered that B-cell epitopes of beta-LG were included in these fragments.
      Furthermore, these four tryptic fragments were also reactive with the antiserum
      to RCM beta-LG. Therefore, the unfolding of the beta-LG molecule is considered
      not to influence the localization of the antibody binding sites on beta-LG.

PMID- 1369987
TI  - Antisense start-ups surveyed.

PMID- 1369988
TI  - New ways to cleave nucleic acids.

PMID- 1369990
TI  - Apropos aprotinin: a review.

PMID- 1369989
TI  - Bovine alpha S1-casein gene sequences direct high level expression of active
      human urokinase in mouse milk.
AB  - We have produced a line of transgenic mice carrying a hybrid bovine alpha S1
      casein/human urokinase gene. Bovine alpha S1-casein gene regulatory sequences
      specifically direct expression of the human urokinase gene in lactating mammary
      tissue from these mice. Urokinase is a 54 kD protein with 9 disulfide bonds that
      is normally synthesized in the kidney; however, the casein/urokinase transgenic
      mice secrete active human urokinase into their milk at concentrations of 1-2
      mg/ml. The mice show no other abnormalities. They give birth to, and nurse,
      normal sized healthy litters. Thus it is possible to produce high concentrations
      of a large, cysteine rich, non-milk protein in the milk of transgenic animals.
      This line of transgenic mice provides a model for the eventual production of
      transgenic farm animals producing high levels of recombinant proteins in their
      milk.

PMID- 1369991
TI  - Monoclonal antibodies specific for human IgE-producing B cells: a potential
      therapeutic for IgE-mediated allergic diseases.
AB  - Monoclonal antibodies (MAbs) specific for surface antigens of lymphocytes are
      being used to target and deplete tumorous or normal lymphocytes in vivo. Here, we
      report evidence for the existence of antigenic epitopes on IgE that are
      accessible on IgE-secreting B cells but not on other cells bearing IgE. Among 42
      murine MAbs specific for human IgE, two were shown by fluorescence flow
      cytometric analyses to bind to IgE-secreting cell lines but not to IgE bound to
      high-affinity IgE.Fc receptors (Fc epsilon RI) on basophils or low-affinity IgE
      receptors (Fc epsilon RII) on other cell types. Neither could they induce
      histamine release from basophils of various donors even under very permissive
      conditions. These antibodies may be useful for targeting IgE-secreting B cells in
      patients suffering from IgE-mediated allergies.

PMID- 1369992
TI  - Some properties and action of poly(glutamic acid) hydrolase II from
      Micromonospora melanosporea IFO 12515.

PMID- 1369993
TI  - Complementarity of peptides specified by 'sense' and 'antisense' strands of DNA.

PMID- 1369994
TI  - Expression in yeast of amino-terminal peptide fusions to hepatitis B core antigen
      and their immunological properties.
AB  - Hepatitis B core protein (HBcAg) is a potent antigen that gives both a T-cell
      dependent and a T-cell-independent antibody response. It has been shown that a
      foreign epitope can be fused to the amino terminus of HBcAg without affecting
      particle integrity, and that the resulting chimaeric cores retain the
      immunogenicity of the foreign epitope. Here we describe the efficient expression
      in yeast of two different chimaeric cores, carrying epitopes of Foot and Mouth
      Disease Virus (FMDV) or human chorionic gonadotrophin (hCG), which are candidates
      for FMD and contraceptive vaccines, respectively. These cores could not be
      produced in E. coli in soluble form but were expressed to high levels in yeast.
      We constructed a yeast expression vector that allows rapid production of
      different chimaeric cores by cloning in cassettes encoding foreign epitopes. Both
      FMDV and hCG-cores were shown to present the epitopes at the surface of the
      particles. The FMDV-cores produced in yeast were efficient inducers of
      neutralising antibodies in guinea-pigs after one low dose.

PMID- 1369996
TI  - Methods for the estimation of the number and quality of animal cells immobilized
      in carbohydrate gels.
AB  - Rapid and reliable methods for the determination of survival, proliferation, and
      metabolic activity of immobilized cells in gels are described. The first method
      is based on an MTT assay that measures qualitatively and quantitatively the
      metabolic activity of the cells. The second method determines cell number by
      measuring the amount of DNA available for Feulgen staining. In the third method,
      two fluorescent dyes are used to differentially stain viable and dead cells. The
      fourth method involves the use of glutaraldehyde to protect the cells when
      melting the gel to facilitate hemocytometric count. The presented techniques
      should help to test the efficiency of the immobilization procedures and to
      monitor the growth and survival of immobilized cells.

PMID- 1369995
TI  - High level expression of tissue inhibitor of metalloproteinases in Chinese
      hamster ovary cells using glutamine synthetase gene amplification.
AB  - We have used a glutamine synthetase (GS) gene as an amplifiable marker in Chinese
      hamster ovary (CHO) cells. GS was combined with an efficient transcription unit
      to produce tissue inhibitor of metalloproteinases (TIMP). Initial transfectant
      cell-lines selected using a GS gene secreted up to 9 micrograms TIMP/10(6)
      cells/24h. After one round of GS gene amplification expression levels of 110
      micrograms TIMP/10(6) cells/24h were achieved. These GS gene amplified CHO cells,
      when adapted to grow in suspension, accumulated 180mg/l in shake flask culture.
      This system therefore provides a rapid method of achieving high level gene
      expression in mammalian cells.

PMID- 1369998
TI  - The polymerase chain reaction.

PMID- 1369997
TI  - Long-term culture of human esophageal explants and cells.
AB  - Human esophageal epithelium obtained from intermediate autopsies (less than 12 h)
      was maintained as cell and explant cultures. In order to develop a serum-free,
      defined media culture model, several medias and additives were evaluated. The
      viability and differentiation of the epithelial cells cultured with serum-free,
      Keratinocyte Growth Media (KGM, Clonetics Co., San Diego, CA) was improved over
      that of esophageal cells and explants cultured in either serum-supplemented CMRL
      1066 (OCM), serum-free additive-supplemented CMRL 1066, or cimetidine
      supplemented CMRL 1066. The KGM component EGF was determined to be trophic for
      esophagus cells on the basis of findings of increased 3H-TdR labelling in KGM
      cultures when compared to control cells grown in KGM without EGF (KBM). The
      morphologic pattern of the cytoskeletal proteins actin, keratin, and vimentin
      were characterized in isolated cell populations. The intermediate filaments,
      keratin, and vimentin were co-expressed in these epithelial cells. Esophageal
      explant viability, differentiation, and outgrowth from 15 cases were also
      evaluated in dishes coated with basement membrane associated proteins. Explants
      cultured in these dishes were equally well-preserved and differentiated. There
      were no significant differences in the explant histology when there was protein
      coating of the culture dishes, although one case showed improved outgrowth with
      laminin coating. A main advantage for using this culture system is that the same
      medium (KGM) can be used for both the culture of explants and isolated epithelial
      cells. Future applications of this model include determining: (1) the effect
      different concentrations of EGF and calcium in the media will have on esophageal
      proliferation and differentiation, and (2) the role of different basement
      membrane associated proteins on the plating efficiency of either isolated or
      outgrowth epithelial esophageal cells.

PMID- 1369999
TI  - Alpha-oligodeoxynucleotides (alpha-DNA): a new chimeric nucleic acid analog.

PMID- 1370000
TI  - Vaxstrate: an anti-reproductive vaccine for cattle.
AB  - This paper describes the development of a vaccine for the prevention of pregnancy
      in female cattle. The vaccine is based on the established principle that
      antibodies to the hypothalamic releasing hormone, gonadotrophin releasing hormone
      (GnRH) block the action of GnRH on pituitary secretion of luteinizing hormone and
      follicle stimulating hormone, leading to gonadal atrophy in mammals. The vaccine
      comprises an immunogenic GnRH:ovalbumin conjugate formulated in a novel double
      adjuvant system and is administered in a two-dose treatment regimen. Field trials
      have confirmed efficacy and the product, Vaxstrate, has now been registered and
      commercialized.

PMID- 1370001
TI  - Target amplification systems in nucleic acid-based diagnostic approaches.
AB  - Currently, PCR is the standard method for target amplification because it is the
      oldest and most developed procedure. However, several new alternative approaches
      for target amplification have recently been developed. Although these new methods
      are at a relatively early stage of development, each has some advantages over
      PCR, such as greater amplification per cycle (TAS, 3SR, Q beta), isothermal
      reaction (3SR), or coupled amplification-mutation detection (LAR/LAS). As a
      result, each may eventually gain widespread use after further development.

PMID- 1370002
TI  - RNA PCR: an application kit.

PMID- 1370003
TI  - Indole alkaloid formation by Catharanthus roseus cells in a biofilm reactor.
AB  - Catharanthus roseus cells producing indole alkaloids were grown in the form of a
      biofilm. Production medium was circulated through the reactor parallel to the
      upper surface of the horizontal biofilm. Sugar consumption and indole alkaloid
      formation were followed to compare the performance of cultures with different
      biofilm thicknesses. Dissolved oxygen concentrations gradients within the
      biofilms were determined at the end of each run. RNA and protein content of the
      cells in the upper and lower layers of the the biofilms were compared. Results
      obtained in the biofilm experiments were compared to those obtained with
      suspension cultures. At optimized biofilm thicknesses, the biofilm reactor was
      more effective than suspension cultures in maximizing indole alkaloid titers.
      This is thought to be due to better cell-cell contact within the biofilm and
      nutrient concentration gradients, which resulted in low growth rates.

PMID- 1370004
TI  - N-laurylbiotinamide as affinity surfactant.
AB  - N-laurylbiotinamide (NLB), which retains strong affinity for the protein avidin,
      was synthesized from biotin and N-laurylamine via the biotin ester of N
      hydroxysuccinimide and characterized by NMR. When the synthesized NLB was used as
      a cosurfactant with AOT to form a reverse micellar system in isooctane, it was
      found to extend the pH range over which avidin can be transferred from a
      continuous aqueous solution to the reverse-micellar phase. This behavior is
      similar to that already reported for a different affinity surfactant, n-octyl
      beta-D-glucopyranoside.

PMID- 1370005
TI  - Removal of a proteolytic activity associated with aggregates formed from
      expression of creatine kinase in Escherichia coli leads to improved recovery of
      active enzyme.
AB  - Expression of creatine kinase (CK) from a Torpedo californica electric organ cDNA
      in Escherichia coli results in an insoluble protein product with no detectable CK
      activity. Although this is a stable aggregate that can be isolated in an enriched
      form by centrifugation, initial attempts to generate enzyme activity by
      denaturing and refolding yielded only minute amounts of active protein. We find
      that these low recoveries are due to proteolysis of the CK during denaturation
      and refolding. While this proteolytic activity is not inhibited by either
      phenylmethanesulfonyl fluoride (PMSF) or EDTA, it can be largely removed from the
      CK aggregate by extraction with a detergent-containing buffer prior to
      denaturation. This treatment improves the recovery of active CK approximately 100
      fold. We have also found similar proteolytic activity associated with the
      aggregate formed when a mutant of bovine pancreatic trypsin inhibitor (BPTI) is
      expressed in E. coli. Discovery of this proteolytic activity in two different
      expression systems suggests that it should be considered as a potential problem
      for recovery of active protein from other inclusion bodies as well.

PMID- 1370006
TI  - Enzyme immobilization by the formation of enzyme coating on small pore-size ion
      exchangers.

PMID- 1370007
TI  - Immobilization of anaerobic thermophilic bacteria for the production of cell-free
      thermostable alpha-amylases and pullulanases.
AB  - For the production of cell-free thermostable alpha-amylases and pullulanases
      various anaerobic thermophilic bacteria that belong to the genera Clostridium and
      Thermoanaerobacter were immobilized in calcium alginate gel beads. The entrapment
      of bacteria was performed in full as well as in hollow spheres. An optimal
      limited medium, which avoided bacterial outgrowth, was developed for the
      cultivation of immobilized organisms at 60 degrees C using 0.4% starch as
      substrate. Compared to non-immobilized cells these techniques allowed a
      significant increase (up to 5.6-fold) in the specific activities of the
      extracellular enzymes formed. An increase in the productivity of extracellular
      enzymes was observed after immobilization of bacteria in full spheres. In the
      case of C. thermosaccharolyticum, for instance, the productivity was raised from
      90 units (U)/10(12) cells up to 700 U/10(12) cells. Electrophoretic analysis of
      the secreted proteins showed that in all cases most of the amylolytic enzymes
      formed were released into the culture medium. Proteins that had a molecular mass
      of less than 450,000 daltons could easily diffuse through the gel matrix.
      Cultivation of immobilized bacteria in semi-continuous and fed-batch cultures was
      also accompanied by an elevation in the concentration of cell-free enzymes.

PMID- 1370008
TI  - Characterization of an alkaline protease from Bacillus sp. no. AH-101.
AB  - The Bacillus sp. no. AH-101 alkaline protease showed higher hydrolysing activity
      against insoluble fibrous natural proteins such as elastin and keratin in
      comparison with subtilisins and Proteinase K. The optimum pH of the enzyme toward
      elastin and keratin was pH 10.5 and pH 11.0-12.0 respectively. The specific
      activity toward elastin and keratin was 10,600 units/mg protein and 3970 units/mg
      protein, respectively. The enzymatic activity was not inhibited by p
      chloromercuribenzoic acid and iodoacetic acid. Carbobenzoxy-glycyl-glycyl-L
      phenylalanyl chloromethyl ketone completely inhibited the caseinolytic activity,
      but 36% elastolytic activity remained. No inhibitory effect on caseinolytic and
      elastolytic activity was shown by tosyl-L-phenylalanyl-chloromethyl ketone, tosyl
      L-lysine chloromethyl ketone, carbobenzoxy-L-phenylalanyl chloromethyl ketone,
      and elastatinal. The amino acid composition and amino terminal sequence of the
      enzyme were determined. The no. AH-101 alkaline protease was compared with
      subtilisin BPN', subtilisin Carlsberg, no. 221, and Ya-B alkaline proteases.
      Extensive sequence homology existed among these enzymes.

PMID- 1370010
TI  - The development and application of a new affinity partitioning system for enzyme
      isolation and purification.
AB  - A reactive water-soluble polymer was synthesized by copolymerizing N
      isopropylacrylamide and glycidyl acrylate. The reactive polymer could react with
      the amino groups of enzymes/proteins or other ligands to form an affinity
      polymer. As a model, the reactive polymer was allowed to react with
      paraaminobenzamidine, a strong trypsin inhibitor. The affinity polymer could
      easily form an aqueous two-phase system with either dextran or pullulan, and the
      phase diagram was compared favorably to that of the well-known polyethylene
      glycol-dextran system. Once trypsin was attracted to the affinity polymer
      dominant phase, the enzyme could be dissociated from the polymer at low pH. Owing
      to the N-isopropylacrylamide units, the affinity polymer could be isolated from
      the solution by precipitation at a low level of ammonium sulfate. The enzyme
      recovery was always greater than 50%, and the affinity polymer could be reused in
      several cycles of affinity partitioning and recovery.

PMID- 1370009
TI  - Enhancement of gene expression by somatic hybridization with primary cells: high
      level synthesis of the hepatitis B surface antigen in monkey Vero cells by fusion
      with primary hepatocytes.
AB  - Vero cells transfected with the S gene encoding the surface antigen (HBsAg) of
      the hepatitis B virus (HBV) synthesize HBsAg at low levels. We have obtained a
      large increase in S gene expression by somatic hybridization of Vero cells with
      primary hepatocytes, which are the natural target cells for HBV infection. Fusion
      with cells other than hepatocytes did not enhance expression of the S gene. The
      Vero/hepatocyte hybrid clones analyzed are stable and have maintained a high
      level of HBsAg synthesis over prolonged periods. Hybrid cell lines may be of
      general interest for the high-level synthesis of proteins using cloned genes.

PMID- 1370011
TI  - A family of expression vectors based on the rrnB P2 promoter of Escherichia coli.
AB  - We describe here the construction of a family of expression vectors, based on the
      P2 promoter of the Escherichia coli rrnB gene by removing regulatory sequences
      downstream of the Pribnow-box and replacing them with the lac operator. These
      vectors allow cloning of foreign genes in such a way that their products are
      synthesized either in the form of fusion proteins of different length, or without
      fusion partners, with or without the original translational initiation signals.
      One of the vectors contains a synthetic oligothreonine-coding sequence that helps
      to stabilize the product of the cloned gene. These vectors allow high-level
      regulated expression of foreign genes, even if their products are relatively
      short peptides.

PMID- 1370012
TI  - Isolation of natural proteins.

PMID- 1370013
TI  - Cationic colloidal gold, a stain for anionic tissue sites.

PMID- 1370014
TI  - Yeast strain development for extracellular enzyme production.

PMID- 1370015
TI  - Characterization of the swelling of a size-exclusion gel.
AB  - The swelling of a dextran gel, Sephadex G-75, was observed in an aqueous
      environment at room temperature by a noninvasive technique that uses light
      microscopy coupled to an image analysis system via a video camera. The rate of
      swelling was found to follow the Tanaka and Fillmore theory, from which the
      overall gel diffusion coefficient was estimated as 6.3 x 10(-7) cm2/s. In
      addition to giving a quantitative measure of gel swelling that could be useful in
      the mechanical design of liquid chromatography columns, this approach provides
      data on wet particle size and particle size range, which is needed for the
      modeling of diffusional and mass transfer effects in size-exclusion
      chromatography. In this context, key observations are that the gel particles are
      nearly spherical with an elliptical shape factor of 0.98 (perfect sphere = 1) and
      that there is little difference between sizes of particles obtained in water, 50
      mM Tris-glycine buffer (pH 10.2), and buffer containing 1 mg/mL protein. The
      diameter of the dry material ranged from 20 to 100 microns, while the hydrated
      particles had diameters of 40-350 microns. The rate of swelling is rapid, with
      50% swelling occurring in about 10 s and swelling to 99% of the final wet
      particle size being obtained in less than 90 s.

PMID- 1370016
TI  - Protective effect of methylcellulose and other polymers on insect cells subjected
      to laminar shear stress.
AB  - The relative sensitivity of two insect cell lines to laminar shear stress was
      determined, and the protective effect of polymers added to the growth media of
      two insect cell lines, Trichoplusia ni (TN-368) and Spodoptera frugiperda (SF-9),
      was evaluated. TN-368 and SF-9 cells were found to be equally sensitive to
      laminar shear stress. Methylcellulose [0.5% (w/v) Dow E4M Methocel] and dextran
      [4.5% (w/v)] increased the resistance of suspended cells to lysis due to laminar
      shear stress by factors of up to 76 and 28, respectively, compared to cells in
      media without additives. It was observed that the protective effect of Pluronic F
      68 was concentration-dependent: 0.2% and 0.3% (w/v) F-68 increased the resistance
      of SF-9 cells to shear stress by factors of 15 and 42, respectively. However,
      increasing the concentration to 0.5% did not significantly increase the cells'
      resistance compared to 0.3% (w/v). F-68 at 0.2% only increased the resistance of
      TN-368 cells by a factor of 6. It is believed that the protection is a result of
      the polymer adsorbing to the cell membrane. None of the polymer additives tested
      had a significant effect on SF-9 or TN-368 growth rate.

PMID- 1370018
TI  - Sample preparation aid for RNA/DNA/protein and other molecular biology studies.

PMID- 1370017
TI  - Potent and specific inhibitors of protein kinase C of microbial origin.
AB  - Potent and specific inhibitors of protein kinase C have been found in
      streptomyces and fungi: Staurosporine, an alkaloid from Streptomyces sp., is the
      most potent inhibitor of protein kinases with an IC50 in the nanomolar range. UCN
      01 (7-hydroxy staurosporine), isolated from Streptomyces sp., is a selective
      inhibitor of protein kinase C with antitumor activity. Calphostin, isolated from
      the fungus Cladosporium cladosporioides, specifically inhibits protein kinase C
      (IC50 = 0.05 microM) without inhibiting other protein kinases. Microbial
      metabolites appear to be a promising source of inhibitors that target signal
      transduction pathways of eukaryotes.

PMID- 1370019
TI  - A comparison of techniques for the quantitation of dot blots.

PMID- 1370020
TI  - Cystic fibrosis--the way forward from the gene.
AB  - Cloning of the cystic fibrosis (CF) gene and elucidation of the physiological
      functions of the encoded protein is a triumph, not only for molecular biology,
      but also for people affected by CF. For them, not only is there now the
      possibility of screening for the commonest mutations, but they may also look
      forward to the prospect of improved therapies being developed.

PMID- 1370021
TI  - Alkaline serine protease produced from citric acid by Bacillus alcalophilus
      subsp. halodurans KP 1239.
AB  - Maximum production of alkaline serine protease by Bacillus alcalophilus subsp.
      halodurans KP 1239 was achieved after 24 h cultivation, at an initial pH of 7.6,
      on a medium containing 1.0% sodium citrate, 0.3% yeast extract, and 0.3% KH2PO4.
      The enzyme was purified to crystalline form from culture broth. The enzyme was
      most active at 60 degrees C and at pH 11.5. The molecular weight, isoelectric
      point and sedimentation coefficient in water at 20 degrees C were estimated as
      29,000, 8.8 and 3.3S, respectively. The N-terminal amino acid sequence was Ala
      Gln-Ser-Val-Pro-Trp-Gly-Ile-Ser-Arg-Val-Gln-Ala-Pro-Ala-Ala- His-Asn-Arg-Gly-.
      The enzyme shared its antigenic determinants with B. alcalophilus ATCC 21522
      serine protease, but not with the subtilisins Carlsberg and BPN'.

PMID- 1370022
TI  - Protein recovery from reversed micellar solutions through contact with a
      pressurized gas phase.
AB  - We describe a new process for the recovery of encapsulated protein from reversed
      micellar solution in concentrated form. The method involves desolubilization of
      the protein by decreasing solvent density through gas dissolution. Under
      appropriate thermodynamic conditions, the micellar water pool can be converted to
      clathrate hydrates. Protein recovery is facilitated by clathrate hydrate
      formation, which causes the desolubilized protein to exist in a solid phase,
      distinct from the micellar supernatant. The process is carried out without any
      ionic strength or pH modification.

PMID- 1370023
TI  - DNA fingerprinting of Streptococcus uberis based on polymorphism of DNA encoding
      rRNA.
AB  - The rRNA gene restriction patterns of strains of Streptococcus uberis and Strep.
      parauberis were determined. Chromosomal DNA was digested with endonucleases and
      probed with radiolabelled DNA complementary to rRNA synthesized by random
      oligonucleotide priming using reverse transcriptase. Reproducible restriction
      patterns were obtained which readily distinguished Strep. uberis and Strep.
      parauberis. In addition, considerable variations in the patterns at the intra
      specific level were observed indicating that rRNA gene restriction profiles are
      of epidemiological, as well as taxonomic value.

PMID- 1370024
TI  - Enterococcus dispar sp. nov. a new Enterococcus species from human sources.
AB  - The partial 16S rRNA sequences of two unknown human enterococcal isolates were
      determined by reverse transcription in an attempt to clarify their taxonomic
      position. The sequence data indicate that they belong to a hitherto unknown
      species of Enterococcus, for which the name Enterococcus dispar sp. nov. is
      proposed. The type strain is NCIMB 13000.

PMID- 1370025
TI  - Automated surface area measurement of cultured cardiac myocytes.
AB  - An automated method for rapidly measuring surface area of individual cardiac
      myocytes was used as an index of myocyte growth. Hearts from 2- to 4-day-old rats
      were digested by overnight incubation in cold trypsin solution. Enriched
      suspensions of myocytes were plated at 2 x 10(5) cells/well in 12-well-culture
      plates. Cells were grown in M199 supplemented with 1%, 10% serum or 10% serum
      plus 10(-7) M norepinephrine. On days 1-4 after plating, cells were fixed in
      Bouin's Solution and stained with Weigert's Iron Hematoxylin and Biebrich Scarlet
      Acid Fuchsin. An inverted microscope, video camera and monitor were coupled to a
      video image processor (Image Technology Corp.). The enhanced image of stained
      heart cells was digitized, and perimeter, length, width and area of each selected
      cell were calculated. One hundred randomly selected cells were measured in each
      of eight wells from each treatment-day group. Areas of individual myocytes varied
      widely in culture dishes and the distribution was skewed toward larger cells. The
      standard deviation increased in proportion to an increase in mean cell area. A
      logarithmic transformation of the data normalized the data and yielded a more
      homogeneous variance. The geometric mean area of heart cells supplemented with 1%
      serum increased only slightly, but significantly, during four days in culture.
      Geometric mean area of cells supplemented with 10% serum increased nearly four
      fold. Supplementing cells with norepinephrine (10(-7) M) in addition to 10% serum
      did not induce a further increase in cell size. This technique has the potential
      to rapidly and objectively monitor heart cell growth following pharmacological or
      toxicological treatments.

PMID- 1370026
TI  - Production of recombinant Von Willebrand factor by CHO cells cultured in
      macroporous microcarriers.
AB  - Recombinant Chinese hamster ovary cells producing Von Willebrand factor have been
      successfully grown in gelatin macroporous microcarriers (Cultispher-G). Serum
      free cultures were maintained in 1, 4, and 10 liter fermentors for more than two
      months. Comparative studies with Cytodex-3 microcarriers have been performed in 1
      liter fermentors. The lower specific Von Willebrand factor productivity of CHO
      cells cultivated on Cultispher-G were offset by higher cell densities (10(7) - 2
      x 10(7) cells/ml). Volumetric Von Willebrand factor productivity was influenced
      by oxygen concentration, and remained stable during scale-up from 1 to 10 liter
      fermentors.

PMID- 1370027
TI  - Large-scale mammalian cell culture: a perspective.

PMID- 1370028
TI  - Continuous cell substrate considerations.
AB  - The debate over the potential risk of tumorigenicity attributable to the use of
      CCL substrates for biologicals production has continued for over 30 years and may
      continue for some time to come. Manufacturers and regulatory agencies are
      developing scientifically based guidelines for such products. It is currently
      possible to follow these guidelines to prepare recombinant biologicals and
      monoclonal antibodies in CCLs which do not pose unreasonable risks. This chapter
      has attempted to describe the scientific tools available to evaluate the putative
      risk of tumorigenicity due to potential virus DNA and protein contaminants. No
      theoretical or experimental basis exists to hypothesize that residual cellular
      protein might present a significant risk of tumorigenicity. The tools are
      certainly adequate for characterization of putative risks due to viruses and DNA
      but are not sufficiently powerful by themselves to assure product safety. The
      subsequent chapter on process validation describes how adequate assurances of
      safety ultimately can be obtained for products of CCLs against theoretical risks
      of tumorigenicity due to putative viruses and DNA. In addition to these
      safeguards, no evidence of tumorigenicity has been found in human or livestock
      animal recipients of the products prepared in CCL substrates. Many patients have
      received inoculations of tissue plasminogen activator, erythropoeitin, factor
      VIII, soluble CD4, GM-CSF, hepatitis B surface antigen vaccine, and various
      monoclonal antibodies and other recombinant products of continuous cell lines in
      clinical trials. For tissue plasminogen activator, large doses of 100 mg per
      patient or more have been used. At the time of writing over 10 kg of CHO-derived
      tissue plasminogen activator has been sold since late 1987 for administration to
      over 100,000 human patients. For recombinant factor VIII, erythropoeitin, and
      soluble CD4 proteins, chronic administration has been employed. Millions have
      received polio and rabies vaccines prepared in continuous Vero cells. In addition
      to this human experience, livestock animals have received annual inoculations of
      foot-and-mouth virus vaccine prepared in BHK-21 (a highly tumorigenic CCL) for up
      to 14 years without effect (69). No effects have been reported which might be
      attributed to oncogenic factors. Thus, scientific tools of characterization and
      principles of process validation are available to protect patients from putative
      risks of tumorigenicity associated with products prepared in CCLs. Increasing
      clinical experience also supports this conclusion.

PMID- 1370029
TI  - Purification and characterization of recombinant proteins. Opportunities and
      challenges.

PMID- 1370030
TI  - Anti-angiogenesis: towards a molecular tourniquet.

PMID- 1370031
TI  - Single cell assay with an automated capillary microinjection system.
AB  - An automated capillary microinjection system with computer controlled positioning
      of the cells and of the capillary, and its applications and advantages are
      described. About 1500 injections are possible in one hour, with high
      reproducibility. In cytoplasmic and nuclear injections more than 90% and 85% of
      the cells are successfully injected. Using FITC-Dextran at a concentration of
      0.5% as a fluorescently labelled coinjection marker, 99% of the cells can be
      retrieved in culture medium even 48 hours after injection. The coordinates of the
      cells are stored in the computer and accuracy in statistical evaluation of
      experiments is improved in comparison to the manual techniques. Methods for
      preparation and handling of glass capillaries were developed resulting in
      reproducible form and significantly reduced clogging rate. The improved
      characteristics offered by this system are demonstrated in studies leading to the
      confirmation of existence of mRNA(s) inhibiting cell proliferation. Functional
      screening by cell injections of cDNA libraries and of size fractionated mRNA
      molecules can be performed efficiently with the automated microinjection system.

PMID- 1370032
TI  - High-level secretion of biologically active aprotinin from the yeast Pichia
      pastoris.
AB  - A synthetic gene encoding aprotinin (bovine pancreatic trypsin inhibitor) was
      fused to the Saccharomyces cerevisiae prepro alpha mating factor leader sequence
      at the dibasic amino acid processing site. Pichia pastoris strains were developed
      to express one or multiple copies of a methanol-inducible expression cassette
      containing the gene fusion. P. pastoris containing a single copy of the vector
      secreted approximately 150 mg/l of immunoreactive protein. A construct bearing
      five copies of the expression cassette secreted 930 mg/l of aprotinin. The
      purified aprotinin molecule was equipotent with the native molecule in a trypsin
      inhibition assay. Protein sequence analysis showed that the alpha factor
      aprotinin fusion was not processed at the basic amino acid residues Lys-Arg.
      Instead, recombinant aprotinin had additional N-terminal amino acids derived from
      prepro alpha factor. The N-terminal extension was variably 11 or 4 amino acids.
      Inclusion of the spacer DNA sequence encoding Glu and Ala between aprotinin and
      the Lys-Arg processing site led to the secretion of a biologically active
      aprotinin containing only a Glu-Ala N-terminal extension.

PMID- 1370033
TI  - Flow cytometric study of cultured mammalian cells.
AB  - Flow cytometry provides a rapid, sensitive and accurate analytical means to
      monitor hybridoma cell cultures. The use of flow cytometry has enabled us to
      study the changes in DNA, RNA, protein, IgG, mitochondrial activity and cell size
      that take place during the growth cycle of batch culture. The temporal changes in
      the levels of these analytes and their heterogeneity have been related to the
      growth/death kinetics. The maximum proportion of S-cells was reached early in the
      growth phase while a population of low fluorescence cells with lower polidy than
      G1, dead cells and fragmented nuclei emerged during the death phase.
      Supplementation with amino acids during the exponential phase prolonged the
      growth cycle by enhancing cell proliferation. The fraction of S/G2 cells was much
      reduced by a reduction in serum concentration but was maintained during the
      prolonged non-proliferating "stationary" phase. The magnitude of Rhodamine 123
      staining showed a consistent and general decrease during late exponential and
      decline phases. This trend was accompanied by an increase in the fraction of the
      Propidium Iodide-stained population which reflected the deteriorating metabolic
      and membrane integrity. Decrease in mean fluorescence intensity for DNA, RNA,
      protein and intracellular IgG was noted at the decline phase. Intracellular
      immunofluorescence was a more reliable indicator of antibody productivity than
      surface immunofluorescence.

PMID- 1370034
TI  - Comparison of human lymphotoxin gene expression in CHO cells directed by genomic
      DNA or cDNA sequences.
AB  - Four recombinant plasmids coding for human lymphotoxin (LT) were constructed with
      genomic DNA (gDNA) or cDNA sequences. The simian virus 40 (SV40) early region,
      which contains the early promoter, an intron of the small-t-antigen-encoding
      gene, and polyadenylation signal sequences, was used for transcriptional and post
      transcriptional regulatory elements in the construction of these plasmids. Two of
      them contained gDNA and the other two contained cDNA. One of the gDNA plasmids
      and one of the cDNA plasmids carry the SV40 intron between the structural gene
      and polyadenylation signal. Transient and stable gene expression levels of these
      plasmids in Chinese hamster ovary (CHO) cells were measured by assaying the
      secreted LT. The plasmid carrying gDNA without the SV40 intron was expressed more
      efficiently than the other three plasmids in both transient and stable gene
      expression assays.

PMID- 1370035
TI  - Features of regenerated clones with or without fusion treatment between
      auxotrophic mutants of Streptomyces antibioticus and their antibiotic
      productivity.
AB  - During experiments on protoplast fusion of complementary auxotrophic mutants (194
      and 11M-21) of Streptomyces antibioticus for strain improvement, the clones
      (typified by F-40) regenerated on minimal regeneration medium (MRM) were found to
      be prototrophs, and to produce an antibiotic different from those produced by the
      parent strain. The protoplast regeneration of each parent was examined as a
      negative control experiment. In the regenerated clones of 194, half of them
      produced actinomycins similar to those produced by the original mutant 194, but
      others (typified by R-20) seemed to produce antibiotics similar to those produced
      by F-40. In the taxonomic characterization of morphological, cultural, and
      physiological properties of each strain, F-40, R-20, and the parent mutant 194
      had no significant differences with a few exceptions. The problem here is whether
      the antibiotic of R-20 is the same as that of F-40, which was first isolated and
      found to be a peptide antibiotic different from actinomycins, with activity
      against Gram-negative and Gram-positive bacteria.

PMID- 1370036
TI  - A genetic system to elicit and monitor antipeptide antibodies without peptide
      synthesis.
AB  - We present a simple and flexible procedure to elicit and assay anti-peptide
      antibodies without peptide synthesis. It consists of expressing the peptide of
      interest in the form of a genetic insert within two different "recipient"
      bacterial proteins. One hybrid protein is used as immunogen for the induction of
      antibodies against the inserted peptide and the other as antigen for monitoring
      the anti-peptide antibodies raised. The two "recipient" proteins used are the
      MalE and the LamB proteins from E. coli. The MalE hybrid proteins can be affinity
      purified on an amylose column using mild nondenaturing conditions and can be
      crystalized for structural studies; LamB hybrid proteins express the inserted
      peptide on the cell surface so that intact bacteria can be used as a reagent. We
      chose, as a model peptide, a B-cell epitope from the pre-S(2) region of Hepatitis
      B virus. With both MalE and LamB hybrid proteins, high titres of anti-preS
      antibodies, able to react with native HBsAg particles, were induced in mice. The
      anti-peptide antibody titres recorded by ELISA were comparable to those obtained
      when either a synthetic peptide, or the hybrid proteins, were used as immobilized
      antigen.

PMID- 1370037
TI  - An epitope on membrane-bound but not secreted IgE: implications in isotype
      specific regulation.
AB  - Immunoglobulins (Igs) on the surface of B lymphocytes are isotype-specific
      immunological markers of the B-cell subsets expressing them. Since these membrane
      bound Igs (mIgs) are antigen receptors, their interaction with antibodies could
      be explored for modulating the activity of specific B-cell subsets. Targeting
      mIgs by antibodies in vivo, however, has not been feasible because of the
      presence of Igs in the circulation and the frequent association of Igs with
      various cell types via Fc receptors. To circumvent these problems, we proposed
      that the extracellular portions of the membrane-anchoring segments of the heavy
      chains of mIgs, referred to as "mIg isotype-specific" or "migis" peptides, may
      provide the antigenic sites for the isotype-specific targeting of B cells in
      vivo. Here we describe the exemplary development of monoclonal antibodies (mAbs)
      recognizing this unique epitope of mIgE.

PMID- 1370038
TI  - Characterization of a novel NTP-dependent 3' exoribonuclease from yeast
      mitochondria.
AB  - We have purified and characterized a novel exoribonuclease that was isolated from
      the mitochondria of Saccharomyces cerevisiae. The enzyme degraded RNA in a 3' to
      5' direction and was dependent on nucleotide triphosphates for activity. All
      eight of the standard ribo- and deoxyribonucleotide triphosphates supported
      activity with an apparent Km ranging from 20 to 90 uM. The enzyme also exhibited
      an RNA-dependent ATPase activity. Evidence suggests that in vivo the enzyme may
      associate with mitochondrial factors which can alleviate the dependence on
      nucleotide triphosphates for enzymatic activity. A model is discussed for the
      role of the enzyme in regulating the turnover of mitochondrial RNAs.

PMID- 1370039
TI  - Epitope mapping in Salmonella flagellar protein.
AB  - The flagellar filaments of bacteria of the genus Salmonella are highly
      immunopotent and antigenically diverse. It is proposed to develop vaccines by
      replacing the flagella of live attenuated Salmonella strains with engineered
      flagellar filament proteins containing foreign epitopes of medical and
      agricultural importance. As an initial step in this process, the major linear
      epitope regions of one filament protein have been identified.

PMID- 1370040
TI  - Effect of cytokines on bovine mammary gland immunity.
AB  - Cytokines are a family of glycoproteins produced by various cell types in
      response to specific stimuli that regulate the immune response. This paper
      reviews recent studies on two different cytokines, each with its own effector
      cell type: interleukin-2 (IL-2), which regulates lymphoid cell responses; and
      granulocyte colony-stimulating factor (GCSF), which regulates neutrophil
      responses. In the first study, administration of IL-2 to the bovine mammary gland
      was found to stimulate the expansion of lymphocyte populations and increase local
      antibody production. In the second study, systemic administration of GCSF
      increased peripheral blood as well as milk neutrophil populations, which afforded
      some protection against Staphylococcus aureus challenge. Results suggest a role
      for cytokines in the control of mastitis in dairy cattle.

PMID- 1370041
TI  - Protein overproduction in Escherichia coli: RNA stabilization, cell disruption
      and recovery with a cross-flow microfiltration membrane.
AB  - After optimizing overproduction of a heterologous gene product (chloramphenicol
      acetyltransferase, CAT) using an RNA stabilization vector * in Escherichia coli
      (Chan et al., 1988), a single step cell disruption and recovery method * for
      obtaining a product stream essentially free of cell debris was developed. The
      behavior of an RNA stabilization plasmid (pKTN-CAT) containing stabilizing intron
      RNA was investigated in two different media both in batch and chemostat modes.
      CAT production of pKTN-CAT was consistently higher (3- to 7-fold) than that of
      the control lacking the stabilization sequences (pK-CAT). Highest CAT production
      was observed for cells grown in minimal medium in batch mode and induced for CAT
      expression early in growth. CAT production of cells grown in the chemostat mode
      exhibited an optimal dilution rate of about 0.1 h-1. Enhancement of protein
      production by pKTN-CAT as compared to pK-CAT tended to be higher when grown in
      rich medium rather than in minimal medium. Presence of the RNA stabilization
      plasmid did not significantly alter the growth rate of the cell. Using a
      combination of chemical treatment (1 mM EDTA) and shear stress resulting from
      cross-flow in a stainless steel microfiltration membrane *, CAT was released into
      the medium through disruption of the E. coli cells. The permeate flux increased
      from 2000 to 9000 kg m-2 h-1 with increasing axial Reynolds number from 10,000 to
      60,000 or increasing mean shear stress from 12 to 47 Pa. The turbidity of the
      permeate was approximately 4% that of the retentate over this range of axial flow
      rates, indicating excellent removal of cell debris. Also, the concentration of
      CAT in the permeate was equal to that in the retentate over this range of axial
      flow rates, indicating complete passage of protein through the membrane. Thus,
      using a combination of chemical treatment and fluid-induced shear stress in a
      cross-flow membrane module, we were able to disrupt and recover the heterologous
      protein in a stream low in debris.

PMID- 1370042
TI  - Xyloglucosides of benzyl and phenethyl alcohols and Z-hex-3-en-1-ol from leaves
      of Alangium platanifolium var. trilobum.
AB  - From a methanolic extract of leaves of Alangium platanifolium var. trilobum,
      benzyl alcohol xylopyranosyl(1---6)glucopyranoside, phenethyl alcohol
      xylopyranosyl(1----6)glucopyranoside and Z-hex-3-en-1-ol (aoba alcohol)
      xylopyranosyl(1----6)glucopyranoside were isolated. Their structures were
      determined mainly by NMR spectroscopy.

PMID- 1370043
TI  - Predicting antigenic sites on proteins.
AB  - The ability to predict antigenic sites on proteins is of major importance for the
      production of synthetic peptide vaccines and synthetic peptide probes of antibody
      structure. Many predictive methods, based on various assumptions about the nature
      of the antigenic response have been proposed and tested. This review will discuss
      the principles underlying the various approaches to predicting antigenic sites
      and will attempt to answer the question of how well they work.

PMID- 1370044
TI  - Application of a nuclease from rye nucleus for structural studies of plant
      ribonucleic acids.
AB  - A new nuclease (Rn) isolated from rye nucleus was applied for the structural
      studies of methionine initiator transfer ribonucleic acid and ribosomal 5S rRNA
      from yellow lupin seeds. The enzyme shows high specificity for some regions of
      both RNAs. The dihydrouridine and ribothymidine loops which are supposed to be
      involved in the tertiary interactions of the methionine initiator tRNA were
      hydrolysed. The anticodon loop is not digested at all. 5S rRNA was digested in
      single stranded regions (loops). The cleavage pattern of the tRNA and 5S rRNA
      obtained with Rn enzyme, suggests not only the high specificity toward single
      stranded regions, but also some dependence on their tertiary structure.

PMID- 1370045
TI  - Purification of glycoproteins by selective transport using concanavalin-mediated
      reverse micellar extraction.
AB  - A novel methodology for coupling liquid-liquid extraction with affinity
      interaction has been developed to selectively and efficiently purify and separate
      glycoproteins. The basis for the separation is the selective extraction of
      glycoproteins from an aqueous solution into a reverse micellar organic phase by
      using concanavalin A (a sugar-binding lectin) as a facilitative carrier.
      Specifically, horseradish peroxidase (a common glycoprotein) can be bound to
      concanavalin A in an aqueous phase and then extracted into an AOT-isooctane
      organic phase with negligible loss in enzyme activity. Virtually no extraction of
      peroxidase occurs in the absence of concanavalin A. Electron spin resonance
      studies have shown that the large lectin-glycoprotein complex (96,000 daltons)
      resides in a nonaqueous environment within the reverse micelle, perhaps at the
      surfactant, water-pool interface; hence, extraction of the large complex is
      feasible. The facilitative extraction has been extended to selective transport of
      peroxidase from a mixture of peroxidase and alkaline phosphatase (a
      nonglycosylated protein). This results in an efficient separation strategy with a
      separation factor of 16.

PMID- 1370046
TI  - Protein isolation by solution-controlled gel sorption.
AB  - Illustrated are the principles for isolating proteins from solution by sorption
      into a polymer gel phase, driven by the addition of a water-soluble polymer to
      the protein solution. The separation is shown to be analogous to conventional two
      phase aqueous extraction. However, the use of a gel phase rather than a solution
      for absorbing the protein makes separation of the protein from the polymer and
      the recycling of the gel phase much simpler. The model system used was linear
      poly(ethylene glycol) (PEG) and dextran gel. Increasing the molecular weight and
      concentration of the PEG favored sorption by the gel of ovalbumin, bovine serum
      albumin, cytochrome c, and hemoglobin. The proteins could be quantitatively
      recovered by immersing the gel in PEG-free solution.

PMID- 1370047
TI  - Towards third-generation whooping cough vaccines.
AB  - To date, the most significant use of recombinant-DNA technologies has been to
      hyperproduce natural molecules that are difficult to obtain in large quantities
      by conventional methods. However, genetic manipulation can also be an efficient
      way to modify the properties of natural molecules in order to make them more
      suitable for human use. In the development of third-generation whooping cough
      vaccines, recombinant-DNA methods were used to remove the enzymatic activity of
      pertussis toxin in order to obtain a new molecule which is devoid of toxicity,
      and can be used for safer vaccination against this disease.

PMID- 1370048
TI  - Common principles in protein folding and antigen presentation.
AB  - The regular recurrence of hydrophobic amino acid residues along a peptide
      sequence determines the formation of a longitudinal hydrophobic strip when the
      peptide forms an alpha-helix. An understanding of the ways this may affect both
      folding of nascent proteins and antigen presentation should facilitate vaccine
      and therapeutics design.

PMID- 1370049
TI  - Quantification of Moraxella bovis haemagglutinating adhesins with monoclonal
      antibodies.
AB  - Six monoclonal antibodies (MAbs) against Moraxella bovis GF 9 were used to
      quantify haemagglutinating adhesins of 16 strains of this organism. The amount of
      each MAb necessary to inhibit one haemagglutinating unit of each strain varied
      between 4 and 0.007 times that required by strain GF 9. Five strains reacted with
      six MAbs, one with five, two with four, one with three, two with two and three
      with none. The procedures used enabled to detect dominant strains candidates for
      vaccines.

PMID- 1370050
TI  - Analysis of polymer molecular weight distributions in aqueous two-phase systems.
AB  - The partitioning of proteins and other biomaterials between two aqueous phases
      containing polyethyleneglycol and dextran is a strong function of the molecular
      weight of the two polymers. Although both polymers are polydispersed (especially
      Dx) most theoretical treatments refer only to the average molecular weight
      (number or mass) and assume that the molecular weight distribution of each
      polymer is the same in both phases. In this work the molecular weight
      distribution of each polymer is the same in both phases. In this work the
      molecular weight distributions of four stock solutions of PEG (4000, 6000, 10,000
      and 20,000) and four stock solutions of Dx (10,000, 40,000, 110,000 and 500,000)
      were measured using High Performance Gel Chromatography. The measurements were
      repeated on the phases formed by the polymer solutions after they were mixed and
      allowed to equilibrate. The molecular weight distribution of the Dx differed in
      the top and bottom phase; both differed from that of the stock solution. Although
      we believe that the molecular weight distribution for PEG also differs in the top
      and bottom phases, we were unable to determine this within the resolution of our
      instruments.

PMID- 1370051
TI  - Enhancement of tissue plasminogen activator production from human normal
      fibroblast IMR-90 cells by limitation of cell growth.
AB  - Tissue plasminogen activator (t-PA) production induced by proteose peptone from
      IMR-90 cells was investigated. Cells monolayered on plastic surfaces had a higher
      ability to produce t-PA per unit cell compared to those grown tri-dimensionally
      on ceramic pieces. Furthermore, confluent monolayers of the cells, which suffered
      contact inhibition and resulted in limited growth, were available for t-PA
      production. Repeated batch production with microcarriers, on which the cells were
      almost confluent monolayers similar to those in T-flasks, was performed.
      Utilization of the cells, which had limited serum in the growth phase, resulted
      in an increase in production. Moreover, dilution of the basal components of the
      medium at initiation of the production phase markedly promoted t-PA production.
      The volumetric productivity was stable for 30 days at 100 IU/cm3 per day. The
      cells were then mostly retained on microcarriers. Thus, an effective and scalable
      method of t-PA production by normal fibroblast cells was developed.

PMID- 1370052
TI  - The peculiar nature of codon usage in primates.

PMID- 1370053
TI  - The linear PCR reaction: a simple and robust method for sequencing amplified rRNA
      genes.
AB  - The linear polymerase chain reaction was used to sequence amplified RNA genes
      from strains of Bacillus, Thermus and Legionella. The technique described is
      simple and reproducible and it works well with double standard product which has
      been PEG precipitated directly from PCR reactions.

PMID- 1370055
TI  - Polymer fractionation in aqueous two-phase polymer systems.
AB  - We consider the effects of the addition of poly(ethylene glycol) (PEG) of
      different molecular weights to aqueous two-phase system of PEG 8000 and dextran
      500. The first purpose of this study was to determine the molecular weight
      partitioning of the polymers themselves so that, for example, aqueous two-phase
      separations using affinity ligands can be improved. The second purpose was to
      examine whether this molecular weight partitioning could be predicted by using
      solution thermodynamic models so that it would be possible to optimize affinity
      partitioning without extensive laboratory work. Experimentally, we find that, by
      increasing the PEG concentration of any molecular weight in the feed, the high
      molecular weight PEG concentration in the dextran-rich phase is reduced. This
      observation can be used to reduce the loss of expensive ligated PEG used in
      affinity partitioning. Further, there is generally good agreement between our
      experimental data and the predictions of a solution thermodynamic model.

PMID- 1370054
TI  - Nine phenethyl alcohol glycosides from Stachys sieboldii.
AB  - Three new phenethyl alcohol glycosides together with six known compounds have
      been isolated from the leaves of Stachys sieboldii. On the basis of chemical and
      spectral analyses, the structures of three new compounds named stachysosides A, B
      and C have been established as 2-(3,4-dihydroxyphenyl)ethyl O-alpha-L
      arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E-caffeoyl-beta-D
      glucopyranoside, 2-(3,4-dihydroxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)
      alpha-L-rhamnopyranosyl- (1----3)-4-O-E-feruloyl-beta-D-glucopyranoside and 2-(3
      hydroxy-4-methoxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L
      rhamnopyranosyl- (1----3)-4-O-E- feruloyl-beta-D-glucopyranoside, respectively.

PMID- 1370057
TI  - Inhibitors of angiogenesis.
AB  - Angiogenesis, the formation of new capillaries, is essential to a number of
      important physiological events, both normal and pathological. Recently, increased
      attention has focused on the purification and characterization of inhibitors of
      this process, because of the potential therapeutic value of angiogenesis
      inhibitors in controlling such "angiogenic diseases" as proliferative
      retinopathy, solid tumors, rheumatoid arthritis, and neovascular glaucoma. We
      review the process of neovascularization and the assays that have been developed
      to study its inhibition in vivo and in vitro. We also discuss the properties of
      different angiogenesis inhibitors and examine the mechanisms by which such
      inhibitors could potentially intervene in the process of neovascularization.

PMID- 1370056
TI  - Retrotransposon gene engineering.
AB  - We have used a mobile mouse VL30 genetic element together with retroviral helper
      cells to efficiently transmit and express chimeric foreign gene sequences in
      murine and human cells. The construct comprised a cDNA copy of retrotransposon
      NVL3, an internal promoter [rat cytosolic phosphoenolpyruvate carboxykinase
      (PEPCK, EC 4.1.1.32)] and an expressed bacterial neomycin resistance gene. Thirty
      to sixty thousand colony forming units/ml (CFU/ml) were recovered from the
      supernatant of mass cultured psi2 helper cells transfected with the recombinant
      retrotransposon plasmid DNA. RNA was expressed from both the VL30 long terminal
      repeat and from the internal PEPCK promoter, resulting in a G418 drug resistance
      phenotype in recipient cells. Integrated VL30 DNA sequences transduced from psi2
      or PA317 retroviral helper cells failed to regenerate detectable replication
      competent virus. Human and rodent recipient cells transduced by the
      retrotransposons appeared to bear intact vector sequences after two rounds of
      transmission by helper cells.

PMID- 1370058
TI  - Inhibitory effect of new imidazole derivatives on the proliferation and nucleic
      acid synthesis of leukemic cells.
AB  - New derivatives of imidazothiazole and imidazobenzothiazole were tested in vitro
      for their potential antiproliferative activity. Four imidazobenzothiazole
      derivatives exhibited a cytotoxic activity against two leukemic cell lines,
      compound I being the most effective. Cell cycle kinetics studies showed that this
      drug delays the progression of cells from G1 to S and G2 M phases. An inhibitory
      effect on DNA and RNA synthesis was also observed. The antiproliferative effect
      of this compound, analogue of immunosuppressive agents, suggested that it could
      be of interest for a therapeutic use and for the synthesis of new derivatives.

PMID- 1370059
TI  - Optimization of cell culture conditions for G-CSF (granulocyte-colony stimulating
      factor) production by genetically engineered Namalwa KJM-1 cells.
AB  - An expression vector for G-CSF, pASLB3-3, was constructed and introduced into
      Namalwa KJM-1 cells (Hosoi et al., 1988), and cells resistant to 100 nM of
      methotrexate (MTX) were obtained. Among them, the highest producer, clone SC57,
      was selected and the productivity of this clone was further characterized. The
      maximal production of G-CSF was at the most 1.8 micrograms/ml/day using a 25 cm2
      tissue culture flask, even though the cell number was above 7 x 10(5) cells/ml.
      The limiting factors at high density were analyzed as the deficiency of
      nutrients, such as glucose, cysteine and serine, and pH control. The depression
      of specific G-CSF productivity per cell under the batch culture conditions was
      overcome by using a perfusion culture system, Biofermenter (Sato, 1983) with
      modifications of nutrients supplementation by a dialysis membrane and/or
      dissolved oxygen (DO) supplementation by microsilicone fibers. ITPSGF medium was
      modified to elevate concentrations of amino acids and glucose by 2.0- and 2.5
      times, respectively. Under the control of pH at 7.4 and DO at 4 ppm, the specific
      G-CSF productivity was not depressed even at high cell density (above 1 x 10(7)
      cells/ml), and the amount of G-CSF reached 41 micrograms/ml. These results
      indicated the possibility of finding the optimum culture conditions for the
      production of recombinant proteins by Namalwa KJM-1 cells.

PMID- 1370060
TI  - Effect of shear stress on cytosolic Ca2+ of calf pulmonary artery endothelial
      cells.
AB  - The purpose of the present study was to determine if hemodynamic shear stress
      increases free cytosolic Ca2+ concentration ([Ca2+]i) of cultured pulmonary
      artery endothelial cells exposed to steady laminar fluid flow in a parallel plate
      chamber. Average [Ca2+]i was estimated by measuring cell-associated fura-2
      fluorescence using microfluorimetric analysis. To determine [Ca2+]i close to the
      membrane surface, 86Rb+ efflux via Ca(2+)-dependent K+ channels was measured.
      Upon initiation of flow or upon step increases in flow, no change in [Ca2+]i was
      observed using fura-2. However, increases in shear stress produced a large,
      transient increase in 86Rb+ efflux. The shear stress-dependent increase in 86Rb+
      efflux was not blocked by either tetrabutylammonium ions (20 mM) or by
      charybdotoxin (10 nM), two specific inhibitors of the Ca(2+)-dependent K+ channel
      of vascular endothelial cells. These results demonstrate that shear stress per se
      has little effect on either the average cytosolic [Ca2+]i as measured by fura-2
      or on [Ca2+]i close to the cytoplasmic surface of the plasmalemma as measured by
      the activity of Ca(2+)-dependent K+ channels.

PMID- 1370061
TI  - Identification of the phenotypic modulation of rabbit arterial smooth muscle
      cells in primary culture by flow cytometry.
AB  - In atherosclerotic lesions, smooth muscle cells (SMC) change from a contractile
      to a synthetic phenotype. The in vivo and in vitro phenotypic transformations of
      SMC have been confirmed by transmission electron microscopy (TEM), but the
      relationship between this change and the cell cycle is still unknown. We
      demonstrated the structural modulation of rabbit arterial SMC in primary culture
      by TEM and immunocytochemistry and simultaneously studied changes in two
      dimensional histograms of the relative DNA and RNA contents by flow cytometry.
      During the first day of primary culture, the cells exhibited the contractile
      phenotype and were composed of a population in the G0 phase characterized by low
      contents of DNA and RNA. On the second day of culture, some of the cells (18.2%)
      had started but not completed the transition into the synthetic phenotype and a
      cell population in the G1A phase with an RNA content above the G0 level appeared
      in almost the same proportion. This cell population could be categorized as an
      "intermediate" type. Moreover, after 3 days when about three-quarters of the
      cells had undergone structural transition, the same proportion of cells had
      entered into the cycling phase, while some cells still remained in the G0 and G1A
      phases. Thus, cell cycle analysis by flow cytometry corresponded well with the
      observations obtained by TEM and immunocytochemistry. These results show that
      flow cytometry can rapidly and relatively conveniently monitor the process of
      phenotypic modulation in SMC and is a useful method for the analysis of such
      transitions.

PMID- 1370062
TI  - Adhesion to thrombospondin by human embryonic fibroblasts is mediated by multiple
      receptors and includes a role for glycoprotein 88 (CD36).
AB  - Fetal embryonic fibroblasts attach and spread on thrombospondin (TSP). Adhesion
      is tight and focal adhesion plaques and "spots" are formed. We have investigated
      the receptors responsible for this adhesion. Unstimulated cells express the
      vitronectin receptor on their surface and this beta 3 integrin molecule
      contributes to adhesion. Another putative receptor for TSP, termed glycoprotein
      (GP) 88, which exists as a cytoplasmic pool in unstimulated cells becomes surface
      expressed when these cells are plated on TSP and localizes to areas of cell
      adhesion. Western blot analysis of cell lysate confirms GP88 as a TSP binding
      protein. Studies with fucoidan indicate that the heparan sulfate proteoglycan,
      known to function as a receptor for TSP, appears to contribute substantially to
      the TSP attachment of these cells and may be the receptor most important in the
      initial phases of TSP interaction.

PMID- 1370063
TI  - Trapped by an incidental finding.

PMID- 1370064
TI  - DNA/RNA synthesis and labelling.
AB  - Reliable methods of machine-aided RNA synthesis have been established to
      complement those for DNA assembly. Oligonucleotides containing thio-modified
      backbones and 2'-O-alkyl sugars head the list of many newly available analogues.
      Biotin, fluorescent agents and many reporter groups can be conveniently
      introduced into oligonucleotides in multiples by phosphoramidite or H-phosphonate
      chemistry.

PMID- 1370065
TI  - Surface presentation of protein epitopes using bacteriophage expression systems.
AB  - Vast libraries of filamentous phage expression vectors that display foreign
      (poly)peptides on the virion surface can be screened by affinity-purifying those
      phage whose displayed foreign peptide binds to an antibody or another binding
      protein. Present libraries display only short random peptides, but work is
      presently underway to create libraries displaying antibodies with a great
      diversity of binding specificities.

PMID- 1370066
TI  - Brain metastases and testicular tumors: long-term survival.
AB  - In this updated and expanded retrospective analysis, the treatment records of 24
      patients with brain metastases from nonseminomatous germ cell testicular tumors
      (NSGCT's) treated at the Indiana University Department of Radiation Oncology from
      1975 through 1988 were reviewed. All patients received standard cisplatin-based
      induction chemotherapy. These patients were divided into three groups. Group 1 (n
      = 10) consisted of patients who presented initially with brain metastases and had
      no prior systemic treatment. Group 2 (n = 4) consisted of those patients who,
      after achieving a complete response (CR) with cisplatin, vinblastine, and
      bleomycin (PVB) +/- doxorubicin, developed a relapse confined to the brain. Group
      3 (n = 10) consisted of those patients who were initially treated with PVB +/-
      doxorubicin or bleomycin, etoposide, and cisplatin (BEP) and eventually developed
      progressive disease and brain metastases. Group 1 was treated with whole brain
      irradiation (WBRT) and PVB +/- doxorubicin or BEP. Group 2 was treated with WBRT,
      cisplatin-based chemotherapy +/- surgical excision. Group 3 was usually treated
      with WBRT palliatively. Six patients, three in Group 1 and three in Group 2, are
      alive and disease-free with follow-up of 5+ years from beginning WBRT. Two
      additional patients in Group 1 survived 5+ years from beginning WBRT before dying
      with disease. No patient in Group 3 survived. Patients with brain metastases who
      have potentially controllable systemic disease should be treated curatively with
      WBRT (5000 cGy/25 fractions) +/- surgical excision and concomitant chemotherapy.

PMID- 1370067
TI  - Changes in brain monoaminergic neurotransmitter concentrations in rat after
      intracerebroventricular injection of streptozotocin.
AB  - The tissue concentrations of the monoaminergic neurotransmitters noradrenaline
      (NA), dopamine, and serotonin (5-HT) and of their major metabolites were measured
      by HPLC and electrochemical detection in several rat brain areas after
      intracerebroventricular injection of streptozotocin (STZ). NA levels were found
      to be decreased in the frontal cortex by 14%, in the entorhinal cortex by 18%,
      and in the striatum by 38%. In the entorhinal cortex, 5-HT levels were decreased
      by 19% and the 5-HT turnover rate, measured as the 5-hydroxyindoleacetic acid/5
      HT ratio, was found to be increased by 48%. These results may be indicative of a
      distinct susceptibility of some neurotransmitters in certain brain areas after a
      more general impairment of brain metabolism by means of intracerebroventricular
      application of the diabetogenic compound STZ.

PMID- 1370068
TI  - Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous
      physical activity and motor skill learning.
AB  - This study compared the morphology of cerebellar cortex in adult female rats
      exposed for 1 month to repetitive exercise, motor learning, or an inactive
      condition. In the exercise conditions, rats that were run on a treadmill or
      housed with access to a running wheel had a shorter diffusion distance from blood
      vessels in the molecular layer of the paramedian lobule when compared to rats
      housed individually or rats that participated in a motor skill learning task.
      Rats taught complex motor skills substantially increased the volume of the
      molecular layer per Purkinje neuron and increased blood vessel number
      sufficiently to maintain the diffusion distance. These results dissociate
      angiogenesis associated with increased neuropil volume (as seen in the motor
      learning group) from angiogenesis associated with increased metabolic demands (as
      seen in the exercise groups). While the volume fraction of mitochondria did not
      differ among groups, the mitochondrial volume fraction per Purkinje cell was
      significantly increased in the motor skill rats. This appears to parallel the
      previously reported increase in synapses and associated neuropil volume change.

PMID- 1370069
TI  - Effects of inhibitors of protein kinase C and calpain in experimental delayed
      cerebral vasospasm.
AB  - Vasospasm was produced in adult mongrel dogs by a two-hemorrhage method, and the
      spastic basilar arteries were exposed via the transclival route on Day 7. Tonic
      contraction was produced in the normal canine basilar arteries by a local
      application of KCl or serotonin after transclival exposure. The exposed spastic
      and tonic basilar arteries then received a topical application of the following:
      1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H-7), a potent inhibitor of
      protein kinase C acting at the catalytic domain; calphostin C, a specific
      inhibitor of protein kinase C acting at the regulatory domain; or calpeptin, a
      selective inhibitor of calpain. Both spastic and tonic basilar arteries were
      effectively dilated by H-7. Calphostin C caused only slight dilation of spastic
      basilar arteries but moderate dilation of tonic basilar arteries. Dilation in
      response to calpeptin was remarkable in the spastic basilar arteries but slight
      in the tonic basilar arteries. The doses of calphostin C and calpeptin required
      to obtain maximum effect were markedly lower in the tonic model than in the
      spastic model. The spastic and tonic models had a similar dose-dependent response
      to H-7 but quite a different response to calphostin C or calpeptin, suggesting a
      difference in the function of protein kinase C and calpain in the two models.
      Furthermore, the effect of calphostin C on the reversal of vasospasm was
      increased significantly after topical treatment with calpeptin. It is suggested
      that the majority of the catalytic domain of protein kinase C is dissociated from
      the regulatory domain, probably by a limited proteolysis with calpain, and is
      markedly activated in vasospasm.

PMID- 1370070
TI  - Humoral hypercalcemia in seminomas.
AB  - Seminomas are germ cell tumors that are rarely associated with hypercalcemia. In
      this report, four cases of seminoma with concomitant hypercalcemia are presented
      and another three from the literature are reviewed. All seven patients exhibited
      hypercalcemia with a normal serum concentration of inorganic phosphorus and no
      evidence of skeletal metastases. The peripheral venous level of parathyroid
      hormone (PTH) was normal in four of the five patients in whom it was measured.
      The serum concentration of calcitriol was elevated in the two patients in whom it
      was measured. After systemic chemotherapy, the serum "corrected" total calcium
      concentration returned to normal and remained normal; the decrease in the levels
      temporally paralleled the decrease in tumor volume. Both patients with elevated
      calcitriol levels remained eucalcemic after treatment of the malignancy,
      suggesting that the increased serum calcitriol level was linked to the
      development of hypercalcemia as this humoral agent was inappropriately elevated
      by patients with this syndrome. In contrast to many forms of malignancy, the
      development of hypercalcemia did not adversely affect the prognosis of the
      patients with seminoma, since all seven patients entered complete remission.
      Hypercalcemia appears to be heretofore unrecognized paraneoplastic syndrome
      associated with seminoma.

PMID- 1370071
TI  - Isolated central nervous system relapse of testicular cancer.
AB  - Central nervous system involvement with testicular cancer usually occurs with
      advanced systemic disease. Isolated CNS disease at relapse is rare. We report a
      patient who developed a solitary brain metastasis with no other systemic disease
      after having achieved a complete response to frontline therapy. After combined
      modality therapy for the CNS disease, the patient has remained disease-free for
      more than 3 years. The literature regarding brain metastases in relapsed
      testicular cancer is reviewed, including nine cases of isolated brain metastases.
      The CNS can be a "sanctuary" site for testicular cancer, and in the unusual
      subset of patients with isolated brain relapse, long-term remission is possible
      with aggressive therapy.

PMID- 1370072
TI  - Peripheral neovascularization of muscle and musculocutaneous flaps in the pig.
AB  - Late loss of free muscle flaps following surgical or accidental trauma to the
      dominant vascular pedicle has been reported. In this study, time-dependent
      ligation of the dominant vascular pedicle was undertaken in denervated latissimus
      dorsi musculocutaneous or muscle-only island flaps in the pig. Muscle flaps were
      covered with a skin graft, and silicon rubber sheets were inserted between the
      flaps and their bases to simulate a poorly vascularized bed. Hemodynamic and
      viability studies were then performed using intravenous fluorescein (skin
      viability), tetrazolium blue (muscle viability), and radiolabeled 15-micron
      microspheres (capillary blood flow). Blood flow did not change in acutely raised
      musculocutaneous flaps (n = 10) but was significantly elevated in acutely raised
      muscle-only flaps (n = 10), suggesting that the skin paddle may steal blood flow
      from the underlying muscle in musculocutaneous flaps. Peripheral
      neovascularization at 1 day to 8 weeks was assessed (n = 30). Viability increased
      during the first week of revascularization and was not different in
      musculocutaneous and muscle-only flaps. Revascularization of muscle-only flaps
      was enhanced compared with musculocutaneous flaps in the 2- to 8-week period.

PMID- 1370073
TI  - Sclerotherapy of malignant pleural effusion through sonographically placed small
      bore catheters.
AB  - Pleural sclerosis after drainage with a small-bore catheter was performed in 21
      patients with malignant pleural effusions. Intrapleural catheters 7- to 24-French
      in size were placed by using sonographic guidance. Tetracycline (18 patients) and
      bleomycin (four patients) were used as sclerosing agents (one patient had both).
      Clinical and radiologic follow-up was available on all patients until they died
      (range, 2 weeks to 25 months; mean, 3.6 months). Pleural sclerosis was successful
      in 15 (71%) of 21 patients. Two patients in whom pleurodesis failed had pleural
      sclerosis repeated, with one success and one failure. All of the failures were in
      patients in whom the amount of chest-tube drainage was more than 100 ml/day.
      Pleurodesis with tetracycline was painful in six patients; no pain was associated
      with use of bleomycin. Small pneumothoraces developed in four patients at the
      time of chest-tube placement, without consequence. A superimposed infection that
      developed in a patient having continuous drainage of pleural fluid was
      successfully treated with antibiotics. Pleural sclerotherapy can be performed
      through sonographically placed small-bore catheters with results comparable to
      those seen with large-bore, surgically placed catheters.

PMID- 1370075
TI  - Intracellular metabolism of 5-formyl tetrahydrofolate in human breast and colon
      cell lines.
AB  - This report describes the intracellular metabolism of 5-formyltetrahydrofolate
      into the various one-carbon substituted folate and polyglutamate pools in a human
      breast (MCF-7) and colon (HCT 116) carcinoma cell line. Metabolism into the one
      carbon substituted pools was found to be time and dose dependent over a
      concentration range up to 50 microM. A 3-fold increase in total intracellular
      folate was noted over a 50-fold concentration range (1-50 microM) of 5
      formyltetrahydrofolate tested in the colon cell line, while in the breast line, a
      6-fold increase was detected over a 500-fold concentration range (0.1-50 microM).
      The level of 5, 10-methylenetetrahydrofolate, which was detectable only in the
      breast cell line, was found to increase by a factor of 10 (1.8 pmol/mg to 17.9
      pmol/mg) over the concentration range studied. The majority of metabolism was
      into the 10-formyltetrahydrofolate and tetrahydrofolate pools in the breast cells
      and into the 5-methyltetrahydrofolate pool in the colon cells. Polyglutamation
      was also time and dose dependent, with a significant proportion of the total pool
      represented by the higher polyglutamate forms (Glu3-Glu5) after 24 h of
      continuous exposure to 5-formyl tetrahydrofolate. Pentaglutamate was the highest
      level noted in both cell lines. The intracellular half-life of the polyglutamate
      forms was inversely related to the length of the polyglutamate tail with half
      lives of 71, 131, 143, 441, and 1167 min for the mono- through pentaglutamate,
      respectively. Finally, up to a 20:1 ratio of the biologically inactive (6R)
      isomer to active (6S) isomer of 5-formyltetrahydrofolate resulted in no effect on
      metabolism into the one-carbon substituted folate pools and only minimal
      decreases in metabolism to the polyglutamate forms. These studies suggest that
      prolonged exposure to even relatively low doses of 5-formyltetrahydrofolate may
      be optimal for intracellular metabolism to the most biologically relevant forms
      for ternary complex formation with thymidylate synthase and fluorodeoxyuradylate,
      since longer exposures result in a greater accumulation of the higher
      polyglutamates.

PMID- 1370074
TI  - Increased sensitivity of human keratinocytes immortalized by human papillomavirus
      type 16 DNA to growth control by retinoids.
AB  - Human papillomavirus (HPV) type 16 (HPV16) is associated with a large percentage
      of cervical malignancies, and HPV16 DNA can immortalize human keratinocytes in
      vitro. The transforming ability of the virus resides primarily in the open
      reading frames E6 and E7. Retinoids are potent modulators of growth and
      differentiation of keratinocytes and have been shown to reverse cervical lesions
      resulting from HPV infection. We compared the sensitivity of normal human
      foreskin keratinocytes (HKc) and four immortalized HKc lines, independently
      obtained by transfection of different normal HKc strains with HPV16 DNA
      (HKc/HPV16), to growth control by retinoic acid (RA). All the HKc/HPV16 lines
      were 10- to 100-fold more sensitive than normal HKc to growth inhibition by RA in
      both clonal and mass culture growth assays. The precursor to RA, retinol, was
      also found to be a more potent inhibitor of growth of HKc/HPV16 than normal HKc,
      while beta-carotene did not inhibit growth of either normal HKc or HKc/HPV16. In
      addition, HKc/HPV16 lines were more sensitive than normal HKc to modulation of
      keratin expression by RA and retinol. No differences were observed in the rate of
      uptake of [3H]RA or [3H]retinol between normal HKc and HKc/HPV16. Dot blot
      analysis of RNA extracted from HKc/HPV16 cultured in the absence or in the
      presence of 10(-7) M RA showed that the expression of the HPV16 open reading
      frames E6 and E7 is reduced 2- to 4-fold by RA. In addition, Northern blot
      analysis demonstrated that RA inhibition of E6 and E7 expression was both dose
      and time dependent. Overall, these results suggest that the increased sensitivity
      of the HKc/HPV16 lines to growth control by RA may be mediated by an inhibition
      of the expression of HPV16 gene products which are required for the maintenance
      of continuous growth.

PMID- 1370076
TI  - Nitroreductases and glutathione transferases that act on 4-nitroquinoline 1-oxide
      and their differential induction by butylated hydroxyanisole in mice.
AB  - These studies concern the initial steps in 4-nitroquinoline 1-oxide (4NQO)
      metabolism in relation to mechanisms of anticarcinogenesis. Butylated
      hydroxyanisole (BHA) administration by a protocol known to inhibit the pulmonary
      tumorigenicity of 4NQO in A/HeJ mice enhanced hepatic and pulmonary activities
      for 4NQO metabolism by two major pathways, conjugative detoxification and
      nitroreductive activation. High-performance liquid chromatography analysis showed
      approximate doubling of two types of glutathione transferase subunits with 4NQO
      conjugating activity in livers of BHA-treated mice. Similar increases were
      observed in hepatic 4NQO-conjugating activity and in Vmax, while Km for 4NQO was
      39 to 43 microM. Pulmonary 4NQO-glutathione transferase activity increased 24 to
      29%. DT diaphorase activity toward 4NQO was elevated 3.3-fold in livers and 2.7
      fold in lungs of BHA-treated mice. However, the predominant 4NQO reductase of
      liver and lung was dicumarol resistant, had a strong preference for NADH, and
      showed little if any response to BHA. This Mr 200,000 enzyme, partially purified
      from livers of Swiss mice, exhibited the stoichiometry of 2-NADH/4NQO expected
      for reduction of 4NQO to 4-hydroxyaminoquinoline 1-oxide. Its high affinity for
      4NQO (Km, 15 microM) signified a much greater influence on 4NQO metabolism than
      DT diaphorase (Km, 208 microM). The dicumarol-resistant 4NQO reductase differed
      from several known cytosolic nitroreductases. The results suggest that protection
      by BHA may result from alteration of the balance between 4NQO activation and
      conjugation.

PMID- 1370077
TI  - [3H]paroxetine binding and serotonin content of rat cortical areas, hippocampus,
      neostriatum, ventral mesencephalic tegmentum, and midbrain raphe nuclei region
      following p-chlorophenylalanine and p-chloroamphetamine treatment.
AB  - The agents p-chlorophenylalanine (PCPA) and p-chloroamphetamine (PCA) deplete
      brain serotonin (5-HT) levels by two different mechanisms; PCPA inhibits the
      enzyme tryptophan hydroxylase, whereas PCA has a neurotoxic action on certain 5
      HT neurons. The parameters of [3H]paroxetine binding to homogenates prepared from
      the cerebral cortex of rats treated with PCPA, PCA, or saline; vehicle were
      investigated. The tissue concentrations of 5-HT and 5-hydroxyindole-3-acetic acid
      (5-HIAA) were also determined by HPLC in the same brain samples. After PCPA
      treatment, neither the maximum binding capacity (Bmax) nor the dissociation
      constant (KD) of [3H]paroxetine for the 5-HT uptake recognition site differed
      from controls despite a substantial reduction in the concentration of 5-HT and 5
      HIAA. In contrast, significant changes in both the Bmax and KD values were
      observed in the cerebral cortex of rats treated with PCA. Furthermore,
      [3H]paroxetine binding and tissue concentrations of 5-HT and 5-HIAA were measured
      in the following different regions of the rat brain: cingulate, parietal, and
      visual cortical areas; dorsal and ventral hippocampus; rostral and caudal halves
      of neostriatum; ventral mesencephalic tegmentum; and midbrain raphe nuclei region
      after administration of PCPA, PCA, or saline vehicle. There was an excellent
      correlation between regional 5-HT levels and specific [3H]paroxetine binding in
      control and PCA-treated rats although this correlation was lost after PCPA
      treatment. Under these conditions, the 5-HT innervation remains unchanged whereas
      the concentration of 5-HT and 5-HIAA is greatly reduced. Thus, [3H]paroxetine
      binding appears to provide a reliable marker of 5-HT innervation density within
      the mammalian CNS.

PMID- 1370078
TI  - Glutamate receptor agonists stimulate nitric oxide synthase in primary cultures
      of cerebellar granule cells.
AB  - The glutamate receptor agonist N-methyl-D-aspartate (NMDA) stimulated a rapid,
      extracellular Ca(2+)-dependent conversion of [3H]arginine to [3H]citrulline in
      primary cultures of cerebellar granule cells, indicating receptor-mediated
      activation of nitric oxide (NO) synthase. The NMDA-induced formation of
      [3H]citrulline reached a plateau within 10 min. Subsequent addition of unlabeled
      L-arginine resulted in the disappearance of 3H from the citrulline pool,
      indicating a persistent activation of NO synthase after NMDA receptor
      stimulation. Glutamate, NMDA, and kainate, but not quisqualate, stimulated both
      the conversion of [3H]arginine to [3H]citrulline and cyclic GMP accumulation in a
      dose-dependent manner. Glutamate and NMDA showed similar potencies for the
      stimulation of [3H]citrulline formation and cyclic GMP synthesis, respectively,
      whereas kainate was more potent at inducing cyclic GMP accumulation than at
      stimulating [3H]citrulline formation. Both the [3H]arginine to [3H]citrulline
      conversion and cyclic GMP synthesis stimulated by NMDA were inhibited by the NMDA
      receptor antagonist MK-801 and by the inhibitors of NO synthase, NG-monomethyl-L
      arginine (MeArg) and NG-nitro-L-arginine (NOArg). However, MeArg, in contrast to
      NOArg, also potently inhibited [3H]arginine uptake. Kainate (300 microM)
      stimulated 45Ca2+ influx to the same extent as 100 microM NMDA, but stimulated
      [3H]citrulline formation to a much lesser extent, which suggests that NO synthase
      is localized in subcellular compartments where the Ca2+ concentration is
      regulated mainly by the NMDA receptor.

PMID- 1370079
TI  - Morphometric analysis of normal, mutant, and transgenic CNS: correlation of
      myelin basic protein expression to myelinogenesis.
AB  - The neurological mutant mice shiverer (shi) and myelin deficient (shimld) lack a
      functional gene for the myelin basic proteins (MBP), have virtually no myelin in
      their CNS, shiver, seize, and die early. Mutant mice homozygous for an MBP
      transgene have MBP mRNA and MBP in net amounts approximately 25% of normal, have
      compact myelin, do not shiver or seize, and live normal life spans. We bred mice
      with various combinations of the normal, transgenic, shi, and shimld genes to
      produce mice that expressed MBP mRNA at levels of 0, 5, 12.5, 17.5, 50, 62.5, and
      100% of normal. The CNS of these mice were analyzed for MBP content, tissue
      localization of MBP, degree of myelination, axon size, and myelin thickness. MBP
      protein content correlated with predicted MBP gene expression. Immunocytochemical
      staining localized MBP to white matter in normal and transgenic shi mice with an
      intensity of staining comparable to the degree of MBP gene expression. An
      increase in the percentage of myelinated axons and the thickness of myelin
      correlated with increased gene expression up to 50% of normal. The percentage of
      myelinated axons and myelin thickness remained constant at expression levels
      greater than 50%. The presence of axons loosely wrapped with oligodendrocytic
      membrane in mice expressing lower amounts of MBP mRNA and protein suggested that
      the oligodendroglia produced sufficient MBP to elicit axon wrapping but not
      enough to form compact myelin. Mean axon circumference of myelinated axons was
      greater than axon circumference of unmyelinated axons at each level of gene
      expression, further evidence that oligodendroglial cells preferentially myelinate
      axons of larger caliber.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370080
TI  - Potassium-induced depolarization of rat telencephalic synaptoneurosomes increases
      [3H]amino-3-hydroxy-5-methylisoxazole-4-propionate receptor binding.
AB  - Potassium-induced depolarization of synaptoneurosomes prepared from rat
      telencephalon was found to increase [3H]amino-3-hydroxy-5-methylisoxazole-4
      propionate ([3H]AMPA) binding to the AMPA receptor. The effect required the
      presence of calcium because it was blocked by the calcium chelator EGTA but was
      not blocked by an antagonist of the N-methyl-D-aspartate receptor,
      aminophosphonopentanoate. The depolarization-induced increase in [3H]AMPA binding
      was markedly reduced by a blocker of voltage-dependent calcium channels,
      verapamil. Saturation kinetic experiments revealed that the increase in [3H]AMPA
      binding produced by potassium depolarization was due to an increase in the
      affinity of the AMPA receptor. These results provide additional support for a
      critical role of calcium in the regulation of the AMPA receptors. The
      synaptoneurosome preparation might represent an interesting tool to determine the
      role of different calcium-dependent enzymes involved in the regulation of the
      AMPA receptor.

PMID- 1370081
TI  - Vestibular compensation affects endogenous phosphorylation of frog brain
      proteins.
AB  - The effect of unilateral labyrinthectomy followed by the process of vestibular
      compensation on the incorporation of radioactive phosphate into frog brain
      proteins was investigated. Phosphoproteins were analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis followed by autoradiography. The
      present data show that unilateral labyrinthectomy affects the incorporation of
      32P into various frog brain proteins. In particular, the phosphorylation of a 20
      kDa protein appeared enhanced during early stages of vestibular compensation (4
      12 days). This 20-kDa protein was shown to be immunologically related to myelin
      basic protein and its phosphorylation was regulated by an endogenous
      calcium/calmodulin-dependent protein kinase. These data might indicate that in
      addition to neuronal components, components of glial origin are also involved in
      biochemical events that lead to functional recovery after neuronal lesions.

PMID- 1370082
TI  - Odontogenic keratocysts: a clinical and histologic comparison of the parakeratin
      and orthokeratin variants.
AB  - Four hundred forty-nine cases of odontogenic keratocyst (OKC) were separated into
      three histologic categories: parakeratinized, orthokeratinized, or a combination
      of the two types. Demographic and clinical data, such as anatomic location and
      recurrence, were obtained from the biopsy forms. Results showed that 86.2% of the
      449 cases were parakeratinized, 12.2% were orthokeratinized, and 1.6% had
      features of both orthokeratin and parakeratin. There were no statistically
      significant differences between orthokeratinized and parakeratinized OKCs when
      age, race, sex, presenting symptoms, and the clinical impression were compared.
      The orthokeratinized OKC was more often associated with an impacted tooth
      (75.7%), as compared with 47.8% for the parakeratinized OKC (P = .001).
      Parakeratinized OKCs recurred in at least 42.6% of the cases, compared with only
      2.2% for orthokeratinized OKCs. This study emphasizes the importance of
      distinguishing between the parakeratin and orthokeratin variants of OKC. In
      addition, data are presented that show the need for longer follow-up than
      previously documented.

PMID- 1370083
TI  - The position of heterologous epitopes inserted in hepatitis B virus core
      particles determines their immunogenicity.
AB  - The nucleocapsid (HBcAg) of the hepatitis B virus (HBV) has been suggested as a
      carrier moiety for vaccine purposes. We investigated the influence of the
      position of the inserted epitope within hybrid HBcAg particles on antigenicity
      and immunogenicity. For this purpose, genes coding for neutralizing epitopes of
      the pre-S region of the HBV envelope proteins were inserted at the amino
      terminus, the amino terminus through a precore linker sequence, the truncated
      carboxy terminus, or an internal site of HBcAg by genetic engineering and were
      expressed in Escherichia coli. All purified hybrid HBc/pre-S polyproteins were
      particulate. Amino- and carboxy-terminal-modified hybrid HBc particles retained
      HBcAg antigenicity and immunogenicity. In contrast, insertion of a pre-S(1)
      sequence between HBcAg residues 75 and 83 abrogated recognition of HBcAg by 5 of
      6 anti-HBc monoclonal antibodies and diminished recognition by human polyclonal
      anti-HBc. Predictably, HBcAg-specific immunogenicity was also reduced. With
      respect to the inserted epitopes, a pre-S(1) epitope linked to the amino terminus
      of HBcAg was not surface accessible and not immunogenic. A pre-S(1) epitope fused
      to the amino terminus through a precore linker sequence was surface accessible
      and highly immunogenic. A carboxy-terminal-fused pre-S(2) sequence was also
      surface accessible but weakly immunogenic. Insertion of a pre-S(1) epitope at the
      internal site resulted in the most efficient anti-pre-S(1) antibody response.
      Furthermore, immunization with hybrid HBc/pre-S particles exclusively primed T
      helper cells specific for HBcAg and not the inserted epitope. These results
      indicate that the position of the inserted B-cell epitope within HBcAg is
      critical to its immunogenicity.

PMID- 1370085
TI  - Human poliovirus receptor gene expression and poliovirus tissue tropism in
      transgenic mice.
AB  - Expression of the human poliovirus receptor (PVR) in transgenic mice results in
      susceptibility to poliovirus infection. In the primate host, poliovirus infection
      is characterized by restricted tissue tropism. To determine the pattern of
      poliovirus tissue tropism in PVR transgenic mice, PVR gene expression and
      susceptibility to poliovirus infection were examined by in situ hybridization.
      PVR RNA is expressed in transgenic mice at high levels in neurons of the central
      and peripheral nervous system, developing T lymphocytes in the thymus, epithelial
      cells of Bowman's capsule and tubules in the kidney, alveolar cells in the lung,
      and endocrine cells in the adrenal cortex, and it is expressed at low levels in
      intestine, spleen, and skeletal muscle. After infection, poliovirus replication
      was detected only in neurons of the brain and spinal cord and in skeletal muscle.
      These results demonstrated that poliovirus tissue tropism is not governed solely
      by expression of the PVR gene nor by accessibility of cells to virus. Although
      transgenic mouse kidney tissue expressed poliovirus binding sites and was not a
      site of poliovirus replication, when cultivated in vitro, kidney cells developed
      susceptibility to infection. Identification of the changes in cultured kidney
      cells that permit poliovirus infection may provide information on the mechanism
      of poliovirus tissue tropism.

PMID- 1370084
TI  - Biological and biochemical activity of v-Crk chimeras containing the SH2/SH3
      regions of phosphatidylinositol-specific phospholipase C-gamma and Src.
AB  - The chicken CT10 virus oncogene product, P47gag-crk, contains SH2/SH3 domains
      that have been identified as conserved domains among proteins involved in signal
      transduction. We studied the functional similarity of the SH2/SH3 domains by
      replacing those of v-Crk with those of phosphatidylinositol-specific
      phospholipase C-gamma, v-Src, or c-Src. The transforming activity of v-Crk was
      partially retained in a mutant with a v-Src SH3 domain but not in the other
      mutants with heterologous SH2/SH3 domains. Mutant viruses with Crk-SH2/SH2'
      domains induced tyrosine phosphorylation of cellular proteins, but mutants with
      phosphatidylinositol-specific phospholipase C-gamma or Src SH2/SH2' domains did
      not. However, the mutant proteins with heterologous SH2/SH2' regions were able to
      weakly associate with some phosphotyrosine-containing proteins in vitro. These
      results indicate that in the context of the P47gag-crk structure, the requirement
      of Crk-SH2/SH3 is more stringent for its activity to induce cell transformation
      than to cause phosphorylation of cellular proteins. The substitution with
      heterologous sequences least perturbs the capacity to bind phosphotyrosine
      containing proteins. In each case, the SH3 domain is more flexible to
      substitution than is the SH2 domain.

PMID- 1370087
TI  - Incomplete removal of the RNA primer for minus-strand DNA synthesis by human
      immunodeficiency virus type 1 reverse transcriptase.
AB  - A synthetic RNA oligonucleotide (15-mer) corresponding to the 3' end of the
      lysine tRNA primer was hybridized to single-stranded DNA containing the human
      immunodeficiency virus type 1 (HIV-1) primer-binding site and extended with a DNA
      polymerase. The resulting structures were used to study primer removal by the
      RNase H activity of HIV-1 reverse transcriptase. The initial cleavage event
      removes the RNA primer as a 14-mer and leaves a single ribonucleotide A residue
      bound to the 5' end of the DNA strand. This result explains the observation by
      several groups that HIV-1 circle junctions contain 4 bp that are not present in
      the integrated provirus instead of the predicted 3 bp. Subsequent cleavage events
      occur at other sites internal to the RNA molecule, and the ribonucleotide A
      residue on the end of the DNA strand is ultimately removed. Therefore, the
      biologically relevant cleavage that produces the 14-mer reflects the kinetics of
      the reaction as well as a specificity for nucleic acid sequence. When the RNA
      oligonucleotide alone was hybridized to the primer-binding site and tested as a
      substrate for HIV-1 RNase H, the cleavage pattern near the 3' end of the RNA was
      altered.

PMID- 1370086
TI  - Colocalization of adeno-associated virus Rep and capsid proteins in the nuclei of
      infected cells.
AB  - The mechanism of adeno-associated virus (AAV) DNA replication was characterized
      both genetically and biochemically. In this study, we used monoclonal and
      polyclonal antibodies to examine the AAV p5 (Rep78 and Rep68) and p19 (Rep52 and
      Rep40) proteins in infected cells. By overexpressing a truncated Rep78 protein in
      Escherichia coli, we obtained monoclonal antibody anti-78/68, which is specific
      for the p5 Rep proteins, and monoclonal antibody anti-52/40, which recognized
      both the p5 and p19 Rep proteins. In single-fluorochrome indirect
      immunofluorescence labeling experiments, the viral Rep proteins were localized in
      distinct intranuclear foci. Analysis of AAV proteins by double-fluorochrome
      indirect immunofluorescence experiments demonstrated that (i) all four AAV Rep
      proteins occupied the same intranuclear compartments and (ii) the Rep and capsid
      proteins colocalized in the nuclei of infected cells. These results suggest that
      replication centers similar to those established by other viruses exist for AAV.
      These reagents should provide a useful tool for further delineation of the
      mechanism of AAV replication in vitro.

PMID- 1370088
TI  - Influenza A virus transfectants with chimeric hemagglutinins containing epitopes
      from different subtypes.
AB  - Influenza virus transfectants with chimeric hemagglutinins were constructed by
      using a ribonucleoprotein transfection method. Transfectants W(H1)-H2 and W(H1)
      H3 contained A/WSN/33(H1N1) (WSN) hemagglutinins in which the six-amino-acid loop
      (contained in antigenic site B) was replaced by the corresponding structures of
      influenza viruses A/Japan/57(H2N2) and A/Hong Kong/8/68(H3N2) (HK), respectively.
      Serological analysis indicated that the W(H1)-H3 transfectant virus reacted with
      antibodies against both the WSN and HK viruses in hemagglutination inhibition and
      plaque neutralization assays. Furthermore, mice immunized with W(H1)-H3
      transfectant virus produced antibodies to the WSN and HK viruses. The results
      demonstrate that influenza virus transfectants can be engineered to express
      epitopes of different subtypes on their hemagglutinins.

PMID- 1370089
TI  - A glutamine residue in the membrane-associating domain of the bovine
      papillomavirus type 1 E5 oncoprotein mediates its binding to a transmembrane
      component of the vacuolar H(+)-ATPase.
AB  - The 44-amino-acid E5 oncoprotein is the major transforming protein of bovine
      papillomavirus type 1. It is a highly hydrophobic polypeptide which dimerizes and
      localizes to the Golgi apparatus and endoplasmic reticulum membranes. Recent
      evidence suggests that E5 modulates the phosphorylation and internalization of
      the epidermal growth factor and colony-stimulating factor 1 receptors and
      constitutively activates platelet-derived growth factor receptors in C127 and
      FR3T3 cells. Although no direct interaction with these growth factor receptors
      has yet been identified, the E5 oncoprotein has been shown recently to interact
      with the hydrophobic 16-kDa component of the vacuolar H(+)-ATPase (16K protein)
      [D. J. Goldstein, M. E. Finbow, T. Andresson, P. McLean, K. Smith, V. Bubb, and
      R. Schlegel, Nature (London) 352:347-349, 1991]. In the current study, we have
      further analyzed the E5-16K protein complex by fast protein liquid chromatography
      and shown that each E5 dimer appears to bind two 16K proteins. In order to define
      the specific amino acid residues of E5 which participate in this binding, mutated
      E5 epitope fusion proteins were analyzed for their ability to coprecipitate 16K
      protein. Transformation-defective mutants containing amino acid substitutions
      within the short hydrophilic carboxyl-terminal domain retained the ability to
      associate with the 16K protein. However, E5 mutants lacking the glutamine residue
      in the hydrophobic domain were markedly inhibited in 16K protein binding. Most
      interestingly, the placement of a glutamine in several random hydrophobic
      sequences facilitated 16K protein binding, defining this residue as a potential
      binding site for the 16K protein component of the proton pump and exemplifying
      the critical role of hydrophilic amino acids for mediating specific interactions
      between transmembrane proteins.

PMID- 1370090
TI  - Specific interactions between rotavirus outer capsid proteins VP4 and VP7
      determine expression of a cross-reactive, neutralizing VP4-specific epitope.
AB  - We previously reported that the expression of rotavirus phenotypes by
      reassortants was affected by recipient genetic background and proposed specific
      interactions between the outer capsid proteins VP4 and VP7 as the basis for the
      phenotypic effects (D. Chen, J. W. Burns, M. K. Estes, and R. F. Ramig, Proc.
      Natl. Acad. Sci. USA 86:3743-3747, 1989). A neutralizing, cross-reactive VP4
      specific monoclonal antibody (MAb), 2G4, was used to probe the protein-protein
      interactions. The VP4 specificity of 2G4 was confirmed by immunoblot analysis.
      MAb 2G4 reacted with both standard (SA11-C13) and variant rotavirus SA11 (SA11
      4F) but did not react with bovine rotavirus B223 as determined by plaque
      reduction neutralization (PRN) and enzyme-linked immunosorbent assay (ELISA).
      When a panel of SA11-4F/B223 and SA11-Cl3/B223 reassortants in purified or crude
      lysate form that had been grown in the presence or absence of trypsin was
      analyzed with MAb 2G4 by PRN and ELISA, the results with some reassortants were
      unexpected. That is, MAb 2G4 reacted with VP4 of SA11 parental origin (4F or C13)
      when it was assembled into capsids with the homologous SA11 VP7 but failed to
      react with VP4 of SA11 assembled into capsids with heterologous B223 VP7.
      Conversely, MAb 2G4 failed to react with VP4 of B223 parental origin when it was
      assembled into capsids with homologous B223 VP7 but did react with B223 VP4
      assembled into capsids with the heterologous SA11 VP7. Similar reactivity was
      observed when 2G4 was used to immunoprecipitate purified double-shelled virions.
      When soluble unassembled viral proteins were analyzed by ELISA, the 2G4 reactive
      pattern was as predicted from the parental origin of VP4. That is, 2G4 reacted
      with the soluble VP4 of reassortants having VP4 from SA11-Cl3 or SA11-4F and
      failed to react with VP4 of B223 origin, regardless of the origin of VP7. PRN and
      ELISA results obtained with nonglycosylated viruses revealed that the unexpected
      reactivity of 2G4 with virus particles was not the result of differential
      glycosylation of VP7 and epitope masking. These results indicate that the 2G4
      epitope existed in the soluble form of VP4 encoded by SA11-Cl3 or SA11-4F but not
      in soluble B223 VP4. On the other hand, in assembled virions, the presentation of
      the 2G4 epitope on VP4 was unexpected in some reassortants and was affected by
      the specific interactions between VP4 and VP7 of heterologous parental origin.

PMID- 1370091
TI  - Comparative analysis of core amino acid residues of H-2D(b)-restricted cytotoxic
      T-lymphocyte recognition epitopes in simian virus 40 T antigen.
AB  - Simian virus 40 (SV40) tumor (T) antigen expressed in H-2b SV40-transformed cells
      induces the generation of Lyt-2+ (CD8+) cytotoxic T lymphocytes (CTL), which are
      involved in tumor rejection, in syngeneic mice. Five CTL recognition sites on T
      antigen have been described by using mutant T antigens. Four of the sites (I, II,
      III, and V) are H-2Db restricted and have been broadly mapped with synthetic
      peptides of 15 amino acids in length overlapping by 5 residues at the amino and
      carboxy termini. The goal of this study was to define the minimal and optimal
      amino acid sequences of T antigen which would serve as recognition elements for
      the H-2Db-restricted CTL clones Y-1, Y-2, Y-3, and Y-5, which recognizes sites I,
      II, III, and V, respectively. The minimal and optimal residues of T antigen
      recognized by the four CTL clones were determined by using synthetic peptides
      truncated at the amino or carboxy terminus and an H-2Db peptide-binding motif.
      The minimal site recognized by CTL clone Y-1 was defined as amino acids 207 to
      215 of SV40 T antigen. However, the optimal sequence recognized by CTL clone Y-1
      spanned T-antigen amino acids 205 to 215. The T-antigen peptide sequence LT223
      231 was the optimal and minimal sequence recognized by both CTL clones Y-2 and Y
      3. Site V was determined to be contained within amino acids 489 to 497 of T
      antigen. The lytic activities of CTL clones Y-2 and Y-3, which recognize a single
      nonamer peptide, LT223-231, were affected differently by anti-Lyt-2 antibody,
      suggesting that the T-cell receptors of these two CTL clones differ in their
      avidities. As the minimal and optimal H-2Db-restricted CTL recognition sites have
      been defined by nonamer synthetic peptides, it is now possible to search for
      naturally processed H-2Db-restricted epitopes of T antigen and identify critical
      residues involved in processing, presentation, and recognition by SV40-specific
      CTL.

PMID- 1370092
TI  - Identification of VP7 epitopes associated with protection against human rotavirus
      illness or shedding in volunteers.
AB  - Sera from 17 of 18 adult volunteers challenged with a virulent serotype 1
      rotavirus strain (D) were examined for prechallenge antibody levels against
      several well-defined rotavirus VP7 and VP4 neutralization epitopes by a
      competitive epitope-blocking immunoassay (EBA) in order to determine whether
      correlates of resistance to diarrheal illness could be identified. The presence
      of prechallenge serum antibody at a titer of greater than or equal to 1:20 that
      blocked the binding of a serotype 1 VP7-specific monoclonal antibody (designated
      2C9) that maps to amino acid residue 94 in antigenic site A on the serotype 1 VP7
      was significantly associated with resistance to illness or shedding (P less than
      0.001) or illness and shedding (P less than 0.01) following challenge with the
      serotype 1 virus. In addition, an EBA antibody titer of greater than or equal to
      1:20 in prechallenge serum against a serotype 3 VP7-specific epitope (defined by
      monoclonal antibody 954/159) that maps to amino acid 94 on the serotype 3 VP7 was
      also significantly associated with resistance to illness or shedding (P = 0.02),
      with a trend for protection against illness and shedding. A trend was also noted
      between the presence of EBA antibody against a cross-reactive VP4 epitope common
      to many human rotavirus strains, including the challenge virus, or a rhesus
      monkey rotavirus strain-specific VP4 antigenic site, and resistance to illness or
      shedding. These data confirm that the presence of serum antibody correlates with
      resistance to rotavirus illness or shedding but, in addition, demonstrate the
      association of antibody to a specific epitope with resistance to illness or
      shedding. These data also suggest that antigenic site A on the rotavirus VP7,
      composed of amino acids 87 to 96, may be involved in the formation of a major
      protective epitope. Further study of the role of this epitope in the development
      of homotypic and heterotypic immunity to rotaviruses following natural or vaccine
      induced infection may be important in the development of strategies for control
      of rotavirus diarrheal disease.

PMID- 1370093
TI  - p53 shares an antigenic determinant with proteins of 92 and 150 kilodaltons that
      may be involved in senescence of human cells.
AB  - A panel of primary human cells and virus-transformed derivatives were tested for
      events that coincide with immortalization. In all primary and precrisis cells,
      two proteins of 92 and 150 kDa that shared an epitope with p53 were found; in
      most of their immortalized derivatives, however, they were absent. Expression of
      these proteins may be involved in senescence.

PMID- 1370094
TI  - A CD4+ cytotoxic T-lymphocyte clone to a conserved epitope on human
      immunodeficiency virus type 1 p24: cytotoxic activity and secretion of
      interleukin-2 and interleukin-6.
AB  - A CD4+ cytotoxic T-lymphocyte (CTL) clone, established from the peripheral blood
      of a human immunodeficiency virus (HIV)-seropositive donor, lysed autologous
      target cells that were infected with a recombinant vaccinia virus containing the
      gag gene of HIV type 1 and target cells pulsed with p24gag construct expressed in
      Escherichia coli. The recognition of the HLA-DQ-restricted epitope by this clone
      was further defined by using overlapping synthetic peptides. The epitope
      recognized by this CD4+ CTL clone (amino acids 140 to 148) overlaps with a CD8+
      epitope and is highly conserved among all isolates of HIV type 1 that have been
      sequenced. Production and secretion of lymphokines such as interleukin-2 and
      interleukin-6 after specific antigenic stimulation were demonstrated by this gag
      specific CD4+ CTL clone.

PMID- 1370095
TI  - Methylation of discrete sites within the enhancer region regulates the activity
      of the Epstein-Barr virus BamHI W promoter in Burkitt lymphoma lines.
AB  - Eight of the nine viral antigens known to be expressed in in vitro Epstein-Barr
      virus (EBV)-transformed B-lymphoblastoid cell lines are downregulated in EBV
      carrying Burkitt lymphomas (BL). Only EBNA1 can be detected in BL biopsies and BL
      derived cell lines that maintain the representative phenotype during culture in
      vitro (group I BL lines). This restricted pattern of viral gene expression is
      accompanied by extensive EBV DNA methylation and can be reversed by treatment
      with the demethylating agent 5-azacytidine. Transcription of the genes encoding
      the six transformation-associated EBNAs can be initiated from one of two
      promoters located in the BamHI C and W regions, respectively, of the virus
      genome. We show that discrete sites within the BamHI W enhancer region are
      methylated in the group I BL lines Rael, Cheptage, and Elijah and become
      unmethylated after 5-azacytidine treatment that induces the expression of EBNA2.
      Demethylation correlates with activation of transcription from the BamHI W
      promoter as determined by S1 protection analysis. Reporter plasmids in which the
      W enhancer sequences were linked to the chloramphenicol acetyltransferase gene
      were active in untreated Rael, Cheptage, and Elijah cells, demonstrating that all
      of the required transcription factors are present in group I BL cells.
      Conversely, in vitro methylation of the enhancer sequences abolished their
      activity. The results suggest that methylation of control regions in the EBV
      genome may play a critical role for the regulation of viral gene expression in
      tumor cells.

PMID- 1370096
TI  - Tunicamycin treatment of CHO cells abrogates multiple blocks to retrovirus
      infection, one of which is due to a secreted inhibitor.
AB  - Chinese hamster ovary (CHO) cells are resistant to infection by all of the major
      classes of murine retroviruses and are partially resistant to infection by gibbon
      ape leukemia virus. Treatment of CHO cells with the glycosylation inhibitor
      tunicamycin rendered these cells susceptible to infection by retroviral vectors
      with ecotropic, xenotropic, and amphotropic host ranges and increased the titer
      of gibbon ape leukemia virus pseudotyped vectors 10-fold. Vectors having a
      polytropic host range did not infect CHO cells in the presence or absence of
      tunicamycin, showing that the effect of tunicamycin was specific and related to
      the pseudotype of the vector. We present evidence for three mechanisms of
      resistance to infection: lack of viral receptors on CHO cells, the presence of
      nonfunctional receptors which can be made functional by treatment with
      tunicamycin, and the secretion of a protein factor that blocks retroviral
      infection of CHO cells. Several criteria indicate that the secreted inhibitor is
      not an interferon, and secretion of this factor was not detected in several other
      cell lines that were examined.

PMID- 1370098
TI  - Medical management of AIDS patients. Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) presents with variable severity in the context of HIV
      infection. Various therapeutic approaches can be taken, and these are determined
      by the extent and location of KS lesions and the severity of tumor-related
      symptoms. New insights into the pathogenesis of KS lesions may provide innovative
      treatment strategies and a more rational basis for the control of this neoplasm.

PMID- 1370099
TI  - Mutagenicity of complex mixtures in Salmonella typhimurium. A report of the
      International Programme on Chemical Safety's Collaborative Study on Complex
      Mixtures.

PMID- 1370097
TI  - Human cytomegalovirus US3 and UL36-38 immediate-early proteins regulate gene
      expression.
AB  - We have established the ability of the human cytomegalovirus (HCMV) UL36-38 and
      US3 immediate-early (IE) gene products to alter gene expression in human cells by
      using transient transfection assays. The cellular heat shock protein 70 (hsp70)
      promoter was transactivated following cotransfection with the HCMV IE regions in
      nonpermissive HeLa cells by UL36-38, US3, or IE1 and in permissive human diploid
      fibroblasts (HFF) by IE1 or IE2. Moreover, hsp70 expression was synergistically
      increased in HeLa cells cotransfected with US3 and UL36, with US3 and UL37, or
      with US3 and UL37x1. The synergistic transactivation of hsp70 expression by US3
      and UL36-38 was not observed in HFF cells. Synergy was also not observed in HeLa
      cells between US3 and UL38, an early gene product encoded by the UL36-38 IE
      locus. Synergistic transactivation of hsp70 expression in HeLa cells required the
      syntheses of UL36-38 and US3 IE proteins, since nonsense mutants were not
      functional. hsp70 expression increased with increasing amounts of transfected US3
      and UL37 DNA and occurred at the level of stable hsp70-promoted RNA. In contrast
      to the broad hsp70 response, promoters from the HCMV UL112 early gene and another
      cellular gene, brain creatine kinase, both responded strongly only to singly
      transfected IE2 in HeLa cells. Nevertheless, IE2 transactivation of the UL112
      promoter was further stimulated by cotransfection of IE1 or of UL36-38 in both
      HeLa and HFF cells. Thus, different patterns of promoter transactivation and
      interactions between HCMV IE gene products in transactivation were found in HFF
      cells and in HeLa cells. These results establish the ability of the HCMV US3 and
      UL36-38 proteins to alter cellular and viral gene expression and are consistent
      with involvement of cellular transcription factors in HCMV IE regulation of gene
      expression.

PMID- 1370100
TI  - Mutagenicity and chemical analysis of sequential organic extracts of airborne
      particulates.
AB  - To obtain insight into the identity of chemicals associated with the mutagenicity
      of United States National Institute of Standards and Technology (NIST) Standard
      Reference Materials SRM 1649 (urban dust) and SRM 1650 (diesel particulate),
      parallel mutagenicity tests and chemical analyses were performed on
      dichloromethane and sequential organic extracts of these samples. SRM 1649 and
      1650 were sequentially extracted with five organic solvents of increasing
      polarity, in order to partition mutagenic components into discrete fractions. The
      solvents (with associated polarity index) were as follows: (1) hexane (0.0); (2)
      hexane:diethyl ether 9:1 (0.29); (3) hexane:diethyl ether 1:1 (1.45); (4) diethyl
      ether (2.9); (5) methanol (6.6). 0.9270 g of SRM 1649, and 0.0510 g of SRM 1650
      were each extracted three times with 8 ml of each of the solvents, the three
      aliquots were pooled, and analysed for target organics or solvent-exchanged into
      DMSO for mutagenicity testing in Salmonella typhimurium strains TA98 and TA100.
      The dichloromethane extracts of SRM 1649 and SRM 1650 contained direct-acting
      mutagens in Salmonella strains TA98 and TA100; SRM 1650 was significantly more
      potent than SRM 1649 in either strain. Addition of S9 caused a large decrease in
      mutagenicity of each extract, although SRM 1650 remained more potent. An
      interesting pattern of mutagenicity was observed for the sequential extracts of
      SRM 1649 and SRM 1650: the mutagenic potency of SRM 1649 extracts increased with
      increasing polarity of the extraction solvent while the response of the SRM 1650
      extracts was the opposite. This suggests that the direct-acting mutagens in SRM
      1650 are unlike those in SRM 1649. The response, though diminished, was largely
      unchanged when S9 was included in the test mixture. Chemical analyses on the
      various extracts were performed using a Hewlett-Packard model 5890 gas
      chromatograph equipped with a model 5970B mass selective detector (GC-MSD), and a
      0.3 microns film thickness cross-linked methyl silicone capillary column (HP
      1909A-101). Selected ion monitoring (SIM) methods were used to analyze for 105
      target compounds including PAHs and nitro-PAHs. Chemical analysis of the
      dichloromethane extracts of SRM 1649 and SRM 1650 identified three main classes
      of compounds: polyaromatic hydrocarbons (PAH), nitro-polyaromatic hydrocarbons
      (NO2-PAHs) and heterocyclics. The concentration of target compounds and the
      proportion of nitro-PAHs and heterocyclic compounds were considerably greater in
      SRM 1650 than in SRM 1649, consistent with the observed differences in their
      mutagenic potency. However, the different responses of the dichloromethane
      extracts in TA98 and TA100 suggest the presence of different (unidentified)
      compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1370101
TI  - Standard reference materials for chemical and biological studies of complex
      environmental samples.
AB  - Standard Reference Materials (SRMs) from the National Institute of Standards and
      Technology (NIST) are often used in methods development and interlaboratory
      comparison studies since they are homogeneous and readily available to the
      scientific community. SRM 1649 (urban dust/organics), SRM 1650 (diesel
      particulate matter), and SRM 1597 (complex mixture of polycyclic aromatic
      hydrocarbons from coal tar) are three environmental samples which have been used
      by the scientific community for these purposes. These SRMs were originally
      developed to assist laboratories in validating analytical procedures for the
      determination of polycyclic organic compounds in complex mixtures. In addition,
      these SRMs have been valuable for the comparison of methodologies for bacterial
      bioassays and the development of bioassay-directed fractionation and bioassay
      directed chemical analysis techniques. Most recently these SRMs were chosen for
      use as test samples in a collaborative study coordinated by the World Health
      Organization--International Programme on Chemical Safety. This paper provides a
      summary of much of the work to date (published and unpublished) on the chemical
      and biological characterization of these three SRMs. Information regarding the
      availability of other NIST SRMs that might be useful for these types of studies
      are provided also.

PMID- 1370103
TI  - Application of a semi-automated SOS chromotest for measuring genotoxicities of
      complex environmental mixtures containing polycyclic aromatic hydrocarbons.
AB  - Soxhlet-extracted samples of standard reference materials (SRMs) 1649 (PAR1:
      urban dust/organics) and 1650 (PAR2: diesel particulate matter) from the U.S.
      Institute of Standards and Technology were tested for induction of SOS functions
      using a semi-automated version of the SOS chromotest with Escherichia coli PQ37.
      Concentrations of 10 polycyclic aromatic hydrocarbons in the extracts were
      determined using reversed-phase HPLC. Only the diesel particulate matter (PAR2)
      extracts expressed SOS induction activity, which decreased when metabolic
      activation was used. Mutagenic PAH compounds (e.g., chrysene) were found in
      higher concentrations in the PAR2 extracts than in the PAR1 extracts but this
      could not explain the genotoxicity while it was mainly exhibited without
      metabolic activation. The direct genotoxic activity of the diesel particulate
      matter sample PAR2 is probably caused by nitroaromatic compounds; this was also
      supported by parallel studies with the Ames/Salmonella assay.

PMID- 1370102
TI  - Mutagenicity studies on complex environmental mixtures: selection of solvent
      system for extraction.
AB  - The mutagenic activities in the Salmonella/microsome assay of dichloromethane
      (DCM) and acetone extracts of complex environmental mixtures were compared. The
      particulate samples used in the IPCS collaborative study were Soxhlet-extracted
      twice with DCM followed by a third extraction with acetone. Compared with the
      mutagenic activity of the first extract, the third (acetone) extract of the urban
      particulate matter showed a relatively high mutagenic activity. In contrast to
      this the third extract of the diesel particulate matter contributed very little
      additional mutagenic activity. Furthermore, 10 filter samples of air particulates
      from a suburban airport area were collected for comparison of the extraction
      efficiency of DCM and acetone. Each sample was divided into two samples of
      identical size followed by extraction with acetone and DCM, respectively. No
      clear difference in the mutagenic activity of these extracts was observed in
      strains TA98 and TA98NR. It is concluded that for ambient air particulates (but
      not emission samples) acetone may extract some mutagenic compounds which are not
      extracted by DCM. The amount of these additional extractable compounds seems to
      depend on the composition of the sample. As DCM extracts are better suited for
      further fractionation and chemical analysis DCM is considered to be the best
      choice for a general solvent system for extraction of complex environmental
      mixtures.

PMID- 1370104
TI  - Activation of pro-mutagens in complex mixtures by rat liver S9 systems.

PMID- 1370106
TI  - Results of the IPCS collaborative study on complex mixtures.
AB  - The International Programme on Chemical Safety (IPCS) sponsored a collaborative
      study to examine the intra- and inter-laboratory variation associated with the
      preparation and bioassay of complex chemical mixtures. The mixtures selected were
      National Institute of Standards and Technology (NIST) Standard Reference
      Materials (SRMs). 20 laboratories worldwide participated in the collaborative
      trial. The participating laboratories extracted the organic portion of two
      particulate samples--an air-particulate sample and a diesel-particulate sample-
      and bioassayed the extracts. The laboratories simultaneously bioassayed a NIST
      prepared extract of coal tar and two control compounds (benzo[a]pyrene, and 1
      nitropyrene). The bioassay method used was the Salmonella/mammalian microsome
      plate-incorporation test using strains TA98 and TA100. Study design also allowed
      for a comparison of sonication and Soxhlet extraction techniques. The mean
      extractable masses for the air particles and diesel particles were approximately
      5% and 17.5%, respectively. The particulate samples were mutagenic in both
      strains with and without activation in all 20 laboratories. For TA100 the with
      and without activation slope values for the air particulate were 162 and 137
      revertants per mg particles, respectively. For TA98 the respective diesel slope
      values were 268 and 269. The mutagenicity slope values for the diesel particles
      ranged from 3090 (TA98, +S9) to 6697 (TA100, +S9) revertants per mg particles.
      The coal tar solution was negative for both strains when exogenous activation was
      not used but was mutagenic in both strains with exogenous activation. The
      benzo[a]pyrene and 1-nitropyrene were used as positive controls and gave results
      consistent with the literature. This paper provides a complete summary of the
      data collected during the collaborative study. Companion papers provide further
      analysis and interpretation of the results.

PMID- 1370105
TI  - Influence of the microsomal inducer and the incubation system on mutagenicity of
      complex mixtures.
AB  - The mutagenicity of SRM 1649 and 1650 was tested in the presence of rat liver S9
      mix which was induced by polychlorinated biphenyl (PCB) or by the combination of
      phenobarbital and 5,6-benzoflavone. The S9 mix induced by PCB activated
      benzo[a]pyrene strongly. The S9 mix induced by phenobarbital-5,6-benzoflavone
      activated the complex mixtures to approximately the same extent as that induced
      by PCB. This finding indicates that phenobarbital-5,6-benzoflavone instead of PCB
      may be suitable as an inducer under some conditions. The preincubation procedure
      for the mutagenicity test was performed by preincubating the test compound, S9
      mix and bacteria for 20 min in a water bath. This procedure was as effective as
      the plate incorporation test.

PMID- 1370108
TI  - Sources of variation in the mutagenic potency of complex chemical mixtures based
      on the Salmonella/microsome assay.
AB  - Twenty laboratories worldwide participated in a collaborative trial sponsored by
      the International Programme on Chemical Safety on the mutagenicity of complex
      mixtures as expressed in the Salmonella/microsome assay. The U.S. National
      Institute of Standards and Technology provided homogeneous reference samples of
      urban air and diesel particles and a coal tar solution to each participating
      laboratory, along with samples of benzo[a]pyrene and 1-nitropyrene which served
      as positive controls. Mutagenic potency was characterized by the slope of the
      initial linear component of the dose-response curve. Analysis of variance
      revealed significant interlaboratory variation in mutagenic potency, which
      accounted for 57-96% of the total variance on a logarithmic scale, depending on
      the sample, strain and activation conditions. Variation among replicate
      extractions of organic material (required for the air and diesel particles) and
      among replicate bioassays within the same laboratory was also appreciable. The
      average potencies for air and diesel particles in laboratories using Soxhlet
      extracts were not significantly different from those in laboratories using
      sonication, although there was larger interlaboratory variation for the Soxhlet
      method. Repeatability (which approximates the coefficient of variation within
      laboratories) ranged from 18 to 40% for air and diesel particles extracted using
      sonication, depending on the strain and activation conditions. Repeatability of
      Soxhlet-extracted air and diesel particles, however, ranged from about 37 to 89%
      including outliers and from about 11 to 31% excluding outliers. Repeatability of
      the coal tar sample and the 2 positive controls was in the range 18-34%.
      Reproducibility (which approximates the coefficient of variation between
      laboratories) was generally at least twice repeatability, and exceeded 100% for
      Soxhlet-extracted air and diesel particles, as well as 1-nitropyrene. Reanalysis
      of the data omitting observations of more than 1500 revertants/plate generally
      had little effect on these results. Elimination of outlying observations had
      limited impact, with the exception of Soxhlet-extracted air and diesel particles.
      In this case, reproducibility of bioassay results was notably improved, due
      largely to the omission of results for replicate extractions which varied more
      than 5-fold within one laboratory. Normalization of the log potency slopes for
      the mixtures by the corresponding slopes for benzo[a]pyrene tended to reduce this
      variation, although variation was increased after normalization by 1-nitropyrene.
      Adjustment for the percentage of organic matter extracted from the air and diesel
      particulate samples had little effect on variation for sonication-extracted
      particles, whereas variation was reduced for diesel particles and increased for
      air particles for Soxhlet.

PMID- 1370107
TI  - Design and implementation of a collaborative study of the mutagenicity of complex
      mixtures in Salmonella typhimurium.
AB  - In 1987, the International Programme on Chemical Safety (IPCS) in collaboration
      with the U.S. Environmental Protection Agency (U.S. EPA) and the U.S. National
      Institute of Standards and Technology (U.S. NIST) initiated an international
      collaborative study of the mutagenicity of complex environmental mixtures in the
      Ames Salmonella typhimurium mutation assay. The objectives of this study were:
      (1) to estimate the inter- and intra-laboratory variability associated with the
      extraction of mixtures for bioassay, (2) to estimate the inter- and intra
      laboratory variability associated with the Salmonella typhimurium bioassay when
      applied to complex mixtures, and (3) to determine whether standard reference
      complex mixtures would be useful in mutagenicity studies and to evaluate whether
      reference or certified mutagenicity values determined from this collaborative
      study should be reported. The complex mixtures used in this study were selected
      from standard reference materials (SRMs) which had previously been issued by the
      U.S. NIST as SRM 1597 (coal tar), SRM 1649 (diesel particulate matter) and SRM
      1650 (urban air particulate matter) with certified values for polycyclic aromatic
      hydrocarbons. These SRM complex mixtures are available to scientists as reference
      standards for analytical chemistry research and are under consideration as SRMs
      for mutagenicity studies of complex environmental mixtures. This paper briefly
      describes the final study design, protocol, selection of the complex mixtures,
      and implementation of this international study.

PMID- 1370109
TI  - Overview, conclusions, and recommendations of the IPCS collaborative study on
      complex mixtures.
AB  - The International Programme on Chemical Safety (IPCS) sponsored an international
      collaborative study to examine the variability associated with the extraction and
      bioassay of standard reference materials (SRMs) that are complex environmental
      mixtures provided by the U.S. National Institute of Standards and Technology
      (NIST). The study was also intended to evaluate the feasibility of establishing
      bioassay reference values and ranges for the SRMs. Twenty laboratories from North
      America, Europe, and Japan participated in the study. As part of the mandatory
      core protocol, each laboratory extracted the organic material from two
      particulate samples and bioassayed these extracts. A coal tar polycyclic aromatic
      hydrocarbon (PAH) solution and two mutagenic control compounds were also
      subjected to bioassay without prior extraction by the participating laboratories.
      The bioassay used was the Salmonella/microsomal plate incorporation assay. For
      the optional portion of the study, a laboratory was free to use the SRMs for any
      type of exploratory research. The primary purpose of the required portion of the
      study was to estimate the intra- and inter-laboratory variability in mutagenic
      potencies of the test materials and to determine whether or not the NIST mixtures
      could be used as reference materials by others performing the Salmonella assay.
      Repeatability (intra-laboratory variance) of the bioassay results ranged from 16%
      to 88% depending on the SRM and the bioassay conditions (tester strain and
      metabolic activation), whereas reproducibility (inter-laboratory variance) ranged
      from 33% to 152%. Between-laboratory variability was the main source of variation
      accounting for approximately 55-95% of the total variation for the three
      environmental samples. Variation in the mutagenic potency of the control
      compounds was comparable, with the exception of 1-nitropyrene for which the
      reproducibility ranged from 127% to 132%. In summary, NIST SRMs provided useful
      materials for an international inter-laboratory study of complex mixtures. By
      establishing both intra- and inter-laboratory variance for the mutagenicity
      results for these materials, the usefulness of these SRMs as reference materials
      for the Salmonella bioassay was established, critical procedures within the
      bioassay protocol were identified, and recommendations for future efforts were
      delineated.

PMID- 1370110
TI  - Characterization of organic extracts from standard reference materials 1649,
      'urban dust/organics,' and 1650, 'diesel particulate matter', using a
      microsuspension assay. A WHO/IPCS/CSCM study.
AB  - Mutagenicity associated with replicate organic extracts from standard reference
      materials 1649 'urban dust/organics' (air particles), and 1650, 'diesel
      particulate matter' (diesel particles), was determined using a Salmonella
      microsuspension assay. The results indicate that the mutagenicity of samples such
      as these can readily be determined using the microsuspension assay with only 5%
      of the mass required for the standard plate incorporation assay. In general, 80%
      of the variation in mutagenic activity was due to the bioassay procedure and 20%
      to the extraction process. Extracts from both samples had primarily direct-acting
      mutagenicity as there were no significant differences in responses with and
      without metabolic activation (S9). The TA98-S9 mean air particles mutagenic
      activities (C.V., %) based on mass of extractable organics or particles were 4.4
      (4.7%) and 0.29 (3.6%) revertants/micrograms, respectively, and for the diesel
      particles were 66 (44%) and 12 (29%) revertants/microgram, respectively. More of
      the observed direct-acting mutagenicity in the diesel particles extracts was due
      to nitro-substituted compounds because there were significant reductions in
      activity with TA98NR (45% of TA98 -S9) and TA98-1,8-DNP6 (21% of TA98 -S9). In
      the air particles extracts, the TA98NR activities were not significantly
      different from TA98 -S9 but the TA98-1,8-DNP6 levels were.

PMID- 1370111
TI  - Salmonella mutagenicity of three complex mixtures assayed with the
      microsuspension technique. A WHO/IPCS/CSCM study.
AB  - In a collaborative study on complex mixtures, three complex mixtures and two pure
      compounds were assayed with the Salmonella microsuspension technique. The two
      pure compounds were benzo[a]pyrene (BaP) and 1-nitropyrene (1-NP). The three
      complex mixtures were standard reference materials (SRMs) from the U.S. National
      Institute of Standards and Technology, SRM 1649, SRM 1650 and SRM 1597. The two
      samples SRM 1649, an urban dust particulate matter, and SRM 1650, a diesel
      particulate matter, were sonicated with dichloromethane. Sample SRM 1597 was an
      extract of a coal tar sample with a complex mixture of polycyclic aromatic
      hydrocarbons. The microsuspension assay was performed with Salmonella strains
      TA98 and TA100 according to Kado et al. (1983) with minor modifications (Lofroth
      et al., 1988). The results showed that the microsuspension technique is a more
      sensitive assay than the plate incorporation method. Depending on sample, strain
      and metabolic condition the mutagenic responses were 3-37 times higher in the
      microsuspension assay than in the conventional plate incorporation assay. The
      microsuspension method is thus useful for environmental samples which are often
      available in only small amounts.

PMID- 1370112
TI  - Results of a comparative study on the Salmonella pre-incubation and plate
      incorporation assays using test samples from the IPCS collaborative study.
AB  - Three complex mixtures (air particles, diesel particles and a coal tar fraction)
      and two pure compounds (benzo[a]pyrene and 1-nitropyrene) were tested in both the
      pre-incubation and the plate incorporation assay employing Salmonella typhimurium
      TA98 and TA100. Each experiment was conducted independently 2 or 4 times in
      duplicate in the presence and absence of metabolic activation. The mutagenic
      activities were calculated by least squares linear regression from the slope of
      the linear portion of each dose-response curve. Although slightly higher
      mutagenic activity was observed in the pre-incubation assay for the two pure
      compounds and with the plate incorporation assay for the diesel particulate
      sample, the overall data from both assays gave similar values and good
      correlations in TA100 and TA98. The results indicate that the pre-incubation
      assay could be used for these samples instead of the plate incorporation assay.

PMID- 1370113
TI  - Genotoxicity of polycyclic aromatic hydrocarbons in Escherichia coli PQ37.
AB  - In the present investigation, 32 polycyclic aromatic hydrocarbons (PAHs) were
      tested for genotoxicity in E. coli PQ37 using the standard tube assay of the SOS
      chromotest. PAHs such as benzo[ghi]fluoranthene, benzo[j]fluoranthene,
      benzo[a]pyrene, chrysene, dibenzo[a,l]pyrene, fluoranthene and triphenylene
      exhibited high genotoxicity when incubated in the presence of an exogenous
      metabolic activation mixture. The results were compared to those obtained with
      the Salmonella/microsome test.

PMID- 1370114
TI  - Genotoxicity of 1,3- and 1,6-dinitropyrene: induction of micronuclei in a panel
      of mammalian test cell lines.
AB  - 1,3-Dinitropyrene (1,3-DNP) and 1,6-dinitropyrene (1,6-DNP) were assessed for
      their potential to increase the frequencies of micronuclei in a panel of test
      cell lines consisting of H4IIEC3/G-, 5L, 5L/r-1,3-DNP1, 208F, V79, V79/r-1,6
      DNP1, HepG2 and BWI-J cells, which have been partially characterized for their
      expression of xenobiotic metabolising enzymes. The micronuclei were analyzed for
      the presence or absence of kinetochores indicating the occurrence of aneuploidy
      or chromosome breakage, respectively. 1,3-DNP caused a substantial increase in
      the frequency of micronuclei only in V79 cells. 1,6-DNP was strongly genotoxic in
      lines H4IIEC3/G-, 208F, V79 and, to a minor degree, in 5L/r-1,3-DNP1. It caused
      the formation of kinetochore-positive as well as kinetochore-negative micronuclei
      in V79 cells but only of kinetochore-negative micronuclei in H4IIEC3/G- and 208F
      cells. 1,6-DNP-induced formation of micronuclei was paralleled by the appearance
      of multinucleated cells. Treatment of V79 cells with 1,3-DNP resulted in the same
      types of damage as treatment with 1,6-DNP, although considerably higher
      concentrations were required. The results show that 1,6-DNP can be highly
      genotoxic in mammalian cells, whereas, at least in the panel of test cell lines
      used, 1,3-DNP possesses only a low genotoxic activity. 1,3-DNP appears to be
      activated to genotoxic products in V79 cells by the same pathway(s) as 1,6-DNP.

PMID- 1370115
TI  - Influence of different occupations with possible mutagenic effects on
      reproduction and level of induced chromosomal aberrations in peripheral blood.
AB  - In a group of 200 dysfertile couples (400 persons), the possible role of
      different occupations in failures of reproduction was assessed. These couples
      were examined from different points of view, classical genetic examination
      (pedigree, kayrotype, etc.) included. The suspected genotoxic effects in the
      personal history were checked also by testing the level of induced chromosomal
      aberrations. A significantly increased level of induced chromosomal aberrations
      was detected in 37 persons, i.e., 9.3% of the whole group under study. The
      average level of induced aberration in these subjects was 6.8%, as opposed to the
      control group (fertile and dysfertile persons without any unusual exposure to
      mutagens) with a mean of 1.58% aberrant cells in peripheral blood. Most of the
      occupations with demonstrated genotoxic effects involve daily contact with
      chemicals of different types. In some persons also intensive therapy in the
      recent past had genotoxic effects.

PMID- 1370116
TI  - Studies on the genotoxicity of monocrotophos in somatic and germ-like cells of
      Drosophila.
AB  - Parryfos, a farm-grade formulation of monocrotophos, was tested for genotoxicity
      in the wing primordial cells and the male germ-line cells of Drosophila
      melanogaster. Larvae of the 2nd or 3rd instar, heterozygous for the wing-cell
      marker mutations mwh and flr3, were exposed to different concentrations of the
      insecticide in the food. The wings of the hatched flies were screened for the
      presence of mutant mosaic spots exhibiting the marker phenotypes. The frequency
      of induction of sex-linked recessive lethal mutations was used to assess
      genotoxic effects in male germ-line cells. The tested compound was genotoxic in
      both the somatic and the germ-line cells of Drosophila.

PMID- 1370117
TI  - Enhancement by butylated hydroxytoluene of the in vitro activation of 3,3'
      dichlorobenzidine.
AB  - Mutagenicity of Salmonella TA98 and covalent binding to DNA of 3,3'
      dichlorobenzidine (DCB) were used to assess the influence of di-tert.-butylated
      hydroxytoluene (BHT) on the in vitro activation of the arylamine by rat hepatic
      S9 metabolic systems. BHT at a concentration of 4 or 20 microM enhanced the
      mutagenicity of DCB by 32 or 21%, respectively, and the covalent binding of DCB
      to added DNA by 76 or 328%, respectively. The antioxidant altered the HPLC
      profile of isolable DCB metabolites, causing a decrease in the formation of three
      metabolites, an increase in the formation of one metabolite, and the formation of
      an entirely new metabolite. BHT inhibited the mutagenicity of the promutagen 2
      acetylaminofluorene (2-AAF) but had no effect on that of the direct-acting
      mutagen 2,4- dinitrophenylhydrazine (DNPH). The results show that BHT enhances
      the mutagenicity of and DNA binding by DCB, in contrast with the predominantly
      inhibitory effect of the antioxidant on the mutagenicity of other chemicals that
      require bioactivation.

PMID- 1370118
TI  - Germinal and somatic mutation induction in Drosophila after treatment of larvae
      with tritiated water.
AB  - The present study was carried out to evaluate the mutagenicity of tritium,
      administered as tritiated water, in Drosophila melanogaster. Larvae were fed on
      tritium-treated medium during their development. Germinal and somatic mutation
      induction was detected by means of the sex-linked recessive lethal and the wing
      spot tests, respectively. Our results show that beta-radiation from tritium is
      able to induce significant increases in the frequency of both germinal and
      somatic mutations.

PMID- 1370119
TI  - Evaluation of the co-mutagenicity of ethanol and delta 9-tetrahydrocannabinol
      with Trenimon.
AB  - The mutagenic potential of chronic treatments of male CF-1 mice with ethanol and
      delta 9-tetrahydrocannibinol (THC), and their comutagenic potential with a known
      mutagenic agent, Trenimon, were examined. This was accomplished by measuring the
      frequency of dominant lethal mutations arising from mating of treated males with
      nontreated females. Adult male mice were treated with 5% (v/v) ethanol as part of
      a liquid diet (28% ethanol-derived calories) for five weeks; 10 mg/kg body weight
      (p.o.) THC every two days for five weeks; a single injection of Trenimon (0.125
      mg/kg, i.p.) on day 28 of diet treatment; and all combinations of treatments. The
      control group was pair-fed a liquid diet in which isocaloric sucrose replaced
      ethanol; these males were also given sesame oil (vehicle for THC) and saline
      (vehicle for Trenimon) on the same schedule as that for the treated males.
      Neither body weights nor hematocrits were adversely affected by any treatment.
      Both ethanol and Trenimon treatments resulted in a small (8-9%; p less than 0.05)
      decrease in testicular weight. The effect of combined treatment with ethanol and
      Trenimon was roughly additive. Treatment with THC had no effect on testicular
      weight. Seminal vesicle weights were not affected by any treatment. Treatments
      were without significant effect on fertility, as measured by the frequency of
      males producing pregnancies. Ethanol and Trenimon treatments produced
      approximately 3- and 7-fold increases, respectively in the frequencies of
      preimplantational loss over that seen for the control group (7.3%), resulting in
      significant ethanol and Trenimon effects (p less than 0.001). No interactive
      effects of ethanol and Trenimon treatments were noted. Frequencies of dead
      fetuses per pregnancy in the ethanol- and Trenimon-treated groups were increased
      approximately 2.5- and 4-fold, respectively, over the control value of
      approximately 16%. However, the effect of combined treatments was not greater
      than that due to Trenimon alone, resulting in Trenimon and ethanol effects (p
      less than 0.001) and ethanol-Trenimon interaction (p less than 0.001). The
      calculated mutation index resulting from each treatment yielded significant (p
      less than 0.001) ethanol- and Trenimon-induced effects. In contrast to effects of
      ethanol and Trenimon treatments, THC, given alone, or in combination with ethanol
      and/or Trenimon, had no effect on either preimplantational loss, fetal mortality
      or the resulting mutation index. The data suggest that chronic ethanol treatment,
      at levels resulting in minimal fertility impairment, increases the frequency of
      dominant lethal mutations. In contrast, chronic treatment with THC, as
      administered in the present study, appears to be without effect.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1370120
TI  - In vivo cytogenetic activity of diphenylhydantoin in mice.
AB  - Diphenylhydantoin was tested in vivo in mice using a variety of cytogenetic
      endpoints to evaluate its genotoxicity. Injected doses of 125, 250 and 500 mg/kg
      failed to increase the number of chromosome aberrations in marrow cells at 17 h
      post-treatment, and 37.5, 75 and 150 mg/kg doses were likewise ineffective at 36
      h. SCEs were significantly increased by doses of 125 mg/kg (but not 250 mg) after
      23 h and modestly, in relation to dose, at 42 h. No increase in the number of
      micronuclei among marrow PCEs was seen following single i.v. injections ranging
      from 0.1 to 20 mg/kg. Three daily i.p. injections of doses up to 70 mg/kg also
      failed to increase the number of micronuclei in either marrow or peripheral blood
      PCEs. Some cytotoxic effect was evident following relatively high doses.

PMID- 1370121
TI  - Clastogenicity of lead chromate particles in hamster and human cells.
AB  - Several insoluble compounds of chromium, such as lead chromate, are respiratory
      carcinogens in experimental animals and suspected to be so in humans. Lead
      chromate induces neoplastic transformation in cultured cells but the mechanism of
      genotoxicity is unknown. We examined the effect of lead chromate on the integrity
      of chromosomes of Chinese hamster ovary (CHO) and human foreskin fibroblasts
      (HFF) after a 24-h exposure. At 0.4 microgram/cm2, 0.8 microgram/cm2, 2
      microgram/cm2 and 8 microgram/cm2 lead chromate particles reduced survival of CHO
      cells to 86%, 62%, 2% and less than 1% respectively. These concentrations induced
      a dose-dependent 4-19-fold increase in the percent metaphases with damage. The
      HFF cells exhibited higher sensitivity in both cytotoxicity and clastogenicity.
      The spectrum of damage observed for both cell types was primarily achromatic
      lesions affecting one or both chromatids. To test for particle dissolution
      effects, CHO cells were treated for 24 h with either clarified medium that had
      been incubated for 24 h with lead chromate particles, or clarified medium that
      had been pre-conditioned by CHO cells treated with lead chromate particles for 24
      h. No damage was detected in these cells, indicating that extracellular
      dissolution into ionic lead and chromate did not contribute to the genotoxicity.
      This is consistent with a previous study in which scanning electron micrographs
      illustrated internalization of the particles. These results suggest that
      clastogenesis may be a mechanism for lead chromate induced carcinogenesis.

PMID- 1370122
TI  - Improved light-microscopical detection of microsporidia spores in stool and
      duodenal aspirates. The Enteric Opportunistic Infections Working Group.
AB  - BACKGROUND: The diagnosis of infection with Enterocytozoon bieneusi, a
      microsporidian organism that causes chronic diarrhea in patients infected with
      the human immunodeficiency virus (HIV), has depended on invasive procedures. We
      have developed a new method to detect microsporidia spores in feces and duodenal
      aspirates. METHODS: Stool was obtained from four HIV-infected patients with
      biopsy-confirmed intestinal microsporidiosis. Slides prepared from
      unconcentrated, formalin-fixed stool specimens were stained with a new
      chromotrope-based technique and examined by light microscopy. Methods of stool
      concentration were also compared. The technique was then evaluated by examining
      215 specimens from 134 HIV-infected persons with or without diarrhea. In
      addition, duodenal aspirates from 10 patients with unexplained chronic diarrhea
      were examined by light microscopy after staining according to the new and the
      traditional techniques. RESULTS: E. bieneusi spores were found in all
      unconcentrated stool specimens from the four patients with microsporidiosis. The
      use of various methods of stool concentration did not improve the detection of
      microsporidia spores. In the prospective study, microsporidiosis was detected in
      samples from 6 of 27 patients with chronic diarrhea, but in none of those from 42
      patients with acute diarrhea or 65 patients without diarrhea. The presence of
      microsporidia spores in stool specimens and duodenal aspirates allowed the
      successful prediction of the presence of microsporidia in small-bowel biopsy
      specimens from all four patients who subsequently underwent endoscopy.
      CONCLUSIONS: E. bieneusi is an important cause of chronic diarrhea in HIV
      infected persons. This new diagnostic technique serves as a practical,
      noninvasive means to detect microsporidia spores in stool specimens and is also
      applicable to the examination of duodenal aspirates.

PMID- 1370123
TI  - Vulvar vestibulitis: significant clinical variables and treatment outcome.
AB  - The subject of vulvar vestibulitis was reviewed in regard to clinical variables
      that may be associated with this problem as well as the success of available
      treatment modalities. Questionnaires were returned by 71 patients diagnosed as
      having vulvar vestibulitis. Identical information was obtained from a comparison
      group of individuals with no clinical or physical findings suggesting this
      diagnosis. A history of recurrent candidiasis and previous condyloma acuminatum
      were the only variables noted more frequently in patients with vestibulitis.
      Among the patients treated by perineoplasty, 66% reported complete or significant
      alleviation of vulvar pain; 78% of the women noted a significant decrease in
      dyspareunia. Of the patients treated with intralesional interferon, six (50%)
      reported significant improvement in dyspareunia. Vulvar vestibulitis is a
      puzzling clinical entity whose etiology is not well understood. Perineoplasty
      still appears to be the treatment of choice in properly selected individuals.

PMID- 1370124
TI  - Elevated maternal serum alpha-fetoprotein: association with placental
      sonolucencies, fetomaternal hemorrhage, vaginal bleeding, and pregnancy outcome
      in the absence of fetal anomalies.
AB  - Elevated maternal serum alpha-fetoprotein (MSAFP) levels have been associated
      with an increased incidence of both placental sonolucencies and pregnancy
      complications. We designed a prospective study to test the hypothesis that the
      presence of these sonolucencies or a positive maternal Kleihauer-Betke stain
      would be associated with an elevated risk of obstetric complications. We enrolled
      95 women with singleton pregnancies, elevated MSAFP, and no evidence of fetal
      anomalies on second-trimester ultrasound evaluation. Placental sonolucencies were
      documented at the time of ultrasound examination, and a maternal Kleihauer-Betke
      stain for fetal cells was obtained on the same day. Complications of pregnancy
      included fetal growth retardation, preterm delivery, late vaginal bleeding (at or
      after the 20th week of gestation), and fetal death. Women with elevated MSAFP had
      an increased incidence of placental sonolucencies, positive maternal Kleihauer
      Betke stains, first-trimester vaginal bleeding, late vaginal bleeding, preterm
      delivery, fetal growth retardation, and fetal death compared with controls.
      Thirty-nine of 95 women with elevated MSAFP (41.1%) had at least one
      complication. In women with elevated levels, neither the presence of placental
      sonolucencies nor a positive Kleihauer-Betke stain correlated with first
      trimester vaginal bleeding, the MSAFP level, or an increased risk of pregnancy
      complications. First-trimester vaginal bleeding was associated with an increased
      risk of preterm delivery in subjects with elevated MSAFP.

PMID- 1370125
TI  - Marek's disease virus-mediated enhancement of avian leukosis virus gene
      expression and virus production.
AB  - Direct interaction between two viruses in coinfected cells may promote
      replication and pathogenesis of one or both virus types. Synergism between
      herpesviruses and retroviruses is an important factor in diagnosis, treatment,
      and prevention of animal and human diseases. In birds, Marek's disease virus
      (MDV) may be an important cofactor in avian leukosis virus induced disease.
      Infection of susceptible cells with non-oncogenic serotype 2 MDV, an avian
      herpesvirus, and Rous-associated virus type 2 (RAV-2 ALV), a leukemogenic avian
      retrovirus, results in enhanced (greater than 3-fold) transcription of retroviral
      genes, relative to infection with ALV alone. A direct relationship between
      concentrations of retroviral gene expression and amount of input MDV suggests
      that MDV-encoded or -induced factors are responsible for enhanced ALV gene
      expression, ultimately leading to increased accumulation of ALV-specific RNA
      (greater than 5-fold) and protein (greater than 10-fold). At lower doses of input
      MDV, ALV virus production increased over 3-fold, relative to cells infected with
      ALV alone. Interactive laser cytometry was used to detect accumulation of both
      MDV and ALV antigens within single cells from coinfected cultures. These results
      suggest a direct role for MDV-encoded or -induced factors in enhancement of ALV
      gene expression and demonstrate the importance of herpesviruses as cofactors in
      retrovirus replication and pathogenesis in coinfected cells.

PMID- 1370126
TI  - Mx genes show weaker primary response to virus than other interferon-regulated
      genes.
AB  - Some interferon (IFN)-regulated genes are induced as a primary response to virus
      as well as secondarily through virus-induced IFN. Here we investigated whether
      this dual control mechanism would also regulate the activity of the human and
      mouse Mx genes that encode proteins with intrinsic antiviral potentials. To
      distinguish between a primary response to virus and a secondary response to virus
      induced IFN, we studied virus-induced Mx gene expression in cell lines that lack
      a functional IFN system and in cells with blocked protein synthesis. In contrast
      to the two IFN-regulated human genes ISG56 and ISG15, the human MxA gene showed
      almost no primary response to Newcastle disease virus (NDV) or influenza virus.
      Similarly, direct activation of the mouse Mx1 gene by NDV or influenza virus was
      not significant in mouse embryo cells or explanted peritoneal macrophages. A
      moderate primary Mx1 response to NDV was observed in the permanent cell line
      L1210. Lack of a strong IFN-independent Mx response to virus indicates that this
      mode of gene regulation does not play a significant role in Mx-mediated
      resistance to viral disease.

PMID- 1370127
TI  - Comoviruses and enteroviruses share a T cell epitope.
AB  - An in vitro murine T cell proliferation assay was used to determine whether an
      antigenic epitope(s) recognized by enterovirus-immune T cells is held in common
      between plant comoviruses and human enteroviruses. Splenocytes isolated from
      C3H/HeJ mice infected with coxsackievirus B3 (CVB3) proliferated in vitro not
      only against a variety of enterovirus (CVB2, CVB3, CVB6, CVA16, PV1) antigens,
      but against comovirus (CPMV, BPMV) antigens as well. Splenocytes from mice
      inoculated with bean pod mottle virus (BPMV) also proliferated in response to
      comoviral and enteroviral antigens in vitro. However, if the viral inocula were
      highly purified prior to inoculation, then the splenocyte response was generated
      only against the group used to inoculate, suggesting that the epitope shared
      between the comoviruses and the enteroviruses resided in the nonstructural
      region. B (nonstructural) and M (structural) genomic segments of CPMV were
      translated in rabbit reticulocyte lysates and used as in vitro antigens.
      Splenocytes from mice inoculated with live CVB3 proliferated in response to the B
      RNA-encoded but not the M-RNA-encoded polypeptides, confirming the nonstructural
      coding region location of the common epitope. Comparison of predicted amino acid
      sequences in the nonstructural coding regions of the comoviruses and
      picornaviruses suggested a potentially immunogenic linear epitope in protein 2C.
      The consensus peptide LEEKGI was synthezized and shown to be immunogenic for both
      BPMV- and CVB3-immune splenocytes.

PMID- 1370128
TI  - Mechanism of HIV spread from lymphocytes to epithelia.
AB  - Contact of human immunodeficiency virus (HIV)-infected MOLT-4 lymphocytes with
      epithelial cells derived from small intestine (I407; Intestine 407) resulted in a
      rapid polar budding of viral particles into an enclosed space formed by
      interdigitating microvilli of the contacting cells. Electron microscopy showed
      that released HIV was taken up into the mucosal cell via three independent
      mechanisms: (1) phagocytosis, (2) coated pits, and (3) direct fusion.
      Morphological evidence suggests that internalized HIV may escape into the
      cytoplasm of the target cell by uncoating at the endosomal membrane. Based on CD4
      antibody binding and CD4 antibody blocking experiments, HIV entry does not appear
      to be mediated by a viral CD4 receptor. Productivity of I407 infection was
      confirmed by virus isolation from cocultured MT-4 lymphocytic cells, reverse
      transcriptase assay, p24 antigen ELISA, in situ HIV mRNA hybridization, and
      Southern dot blot analysis. Contrary to infection with free virus, the cell-to
      cell infection was not blocked by anti-gp120 or antiviral serum from HIV-positive
      individuals. It appears that HIV transmission within the confined space between
      contacting cells enables HIV to evade immune protection provided by neutralizing
      antibodies. Our results reveal a mechanism of HIV infection of epithelial cells
      which is triggered by cell-cell contact. Furthermore, these observations offer an
      insight into the cellular sequence of events which may take place during sexual
      transmission of HIV across an intact epithelial barrier.

PMID- 1370129
TI  - HIV-1 gene rev responsible for accumulated heterodisperse RNAs seen in infected T
      cells.
AB  - To analyze which gene of HIV-1 was responsible for the high accumulation of
      "heterodisperse RNAs" in virally infected T-cells, Northern blot analysis was
      performed. Total RNA from inducible cell lines expressing the envelope protein of
      HIV-1, or the regulatory gene rev, were blotted and hybridized with an Alu probe
      that detects heterodisperse RNAs. Results show that the rev gene is responsible
      for the accumulation of cellular heterodisperse RNAs seen earlier in HIV-1
      infected T-cells.

PMID- 1370130
TI  - Domains of herpes simplex virus I glycoprotein B that function in virus
      penetration, cell-to-cell spread, and cell fusion.
AB  - Herpes simplex virus 1 glycoprotein B (gB) is one of 10 glycoproteins in the
      virion envelope and in the membranes of infected cells. It is required for
      infection of cells in culture and functions in penetration of the cell by fusing
      the virion envelope with the plasma membrane. In studies to map the functional
      domains on HSV-1 gB, we reported that epitopes of potent neutralizing antibodies
      cluster in three major antigenic domains, D1, D2, and D5a. D1 contains continuous
      epitopes in the very amino terminus of gB. D2 comprises discontinuous epitopes
      that are assembled on gB derivatives 457 amino acids in length. D5a contains
      discontinuous epitopes that map between amino acids 600 and 690. We have now
      analyzed the function of these domains in virion infectivity by a detailed
      examination of the effects of 16 neutralizing antibodies on virion adsorption,
      penetration, plaque development, and cell fusion. Our results are as follows. (i)
      Ten antibodies with complement-independent neutralizing activity blocked
      penetration of virions into cells but not their adsorption to the cell surface.
      Treating cell-bound, neutralized virus with the fusogenic agent polyethylene
      glycol promoted their entry into cells. (ii) Ten antibodies with complement
      dependent and -independent neutralizing activity interfered with plaque
      development by preventing spread of virus from infected to neighboring uninfected
      cells. (iii) Nine neutralizing antibodies, all complement-independent, prevented
      cell fusion induced by strain HFEM syn. We conclude that domains mapping in three
      regions of gB function in penetration of virions into cells, and that most
      neutralizing antibodies to these domains also block cell-to-cell spread of virus
      and cell fusion. The findings that three complement-independent neutralizing
      antibodies that blocked penetration did not inhibit plaque development, and that
      only one of these blocked cell fusion, indicate that the cell-to-cell spread of
      virus and cell fusion are related processes, but not identical to the penetration
      function.

PMID- 1370131
TI  - Epitopic regions recognized by monoclonal antibodies against rat brain
      hexokinase: association with catalytic and regulatory function.
AB  - Using direct and competitive epitope mapping methods, 23 monoclonal antibodies
      (Mabs) against rat brain hexokinase (ATP:D-hexose 6-phosphotransferase, EC
      2.7.1.1) were divided into nine groups, each recognizing epitopes within defined
      surface regions of the N- or C-terminal domains; the latter have been associated
      with regulatory or catalytic functions, respectively. Reactivity of Mabs with the
      isolated domains was also studied. Based on the effect of various ligands on
      immunoreactivity, specific regions involved in ligand-induced conformational
      changes were identified. Adjacent epitopic regions, designated Regions F and G
      and located in the N- and C-terminal domains, respectively, were selectively
      affected by inhibitory hexose 6-phosphates (or analogs), marking these regions as
      being involved in transmission of the conformational signal from the regulatory N
      terminal domain to the catalytic C-terminal domain. Consistent with this, the Ki
      for inhibition of the enzyme by the glucose 6-phosphate analog, 1,5
      anhydroglucitol-6-phosphate, was markedly increased by Mabs binding in these
      regions, but unaffected by Mabs binding elsewhere in the molecule. Reactivity
      with Mabs recognizing conformationally sensitive epitopes in Region H of the C
      terminal domain was greatly decreased by binding of substrate hexoses that induce
      closure of a cleft in the catalytic domain; selective recognition of the "open
      cleft" conformation, thereby preventing closure of the cleft required for
      progression of the catalytic cycle, can account for the marked decrease in Vmax
      that results from binding of these Mabs. Reactivity with Mabs binding to Region H
      was also decreased in the presence of inhibitory hexose 6-phosphates, implying
      that cleft closure was also induced by the latter; this is consistent with the
      suggestion that limitation of access to the C-terminal ATP binding site,
      resulting from cleft closure, is a factor in inhibition of the enzyme.

PMID- 1370132
TI  - Betaine:homocysteine methyltransferase from rat liver: purification and
      inhibition by a boronic acid substrate analog.
AB  - Betaine:homocysteine methyltransferase (BHMT) from rat liver has been highly
      purified by an efficient procedure requiring only two chromatographic steps:
      Sephadex G-100 chromatography and fast protein liquid chromatography
      chromatofocusing. A 170-fold purification and 7.5% overall yield were achieved.
      Chromatofocusing yielded three active forms of BHMT with pI values near 8.0, 7.6,
      and 7.0. The subunit molecular weight of each active form is 45,000 Da as
      determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the
      native enzyme has a molecular weight of 270,000 as determined by exclusion
      chromatography. The stability of the purified enzyme was found to be potentiated
      by the presence of 1 mM dimethylglycine and 1 mM homocysteine. Boronate analogs
      of betaine (pinanyl N,N,N-trimethylaminomethaneboronate) (4) and dimethylglycine
      (pinanyl N,N-dimethylaminomethaneboronate) were synthesized from pinanyl
      iodomethaneboronate (3) and trimethylamine or dimethylamine, respectively. The
      free acid of the betaine analog (5) was reversibly generated from (4). The
      inhibition of BHMT by (5) appears competitive with a Ki = 45 microM. Since the Km
      for betaine measured with the purified enzyme is near 0.1 mM, the boronic acid
      analog of betaine appears to function effectively as a substrate analog inhibitor
      of BHMT. The analog does not appear to act as a methyl donor to homocysteine when
      (5) is substituted for betaine in the enzyme reaction. In addition, an enzyme
      assay based upon C3-cyano reverse phase HPLC detection of the o-phthalaldehyde
      derivative of methionine was developed as an alternative to the standard
      radiochemical assay. Betaine:homocysteine methyltransferase in the picomole range
      can be quantitated using this assay as indicated by a linear response of enzyme
      activity to protein concentration.

PMID- 1370133
TI  - Multivariate analysis of serum tumor markers for diagnosis of skeletal
      metastases.
AB  - Serum tumor markers, including carcinoembryonic antigen (CEA), alpha-fetoprotein
      (AFP), carbohydrate antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9),
      cancer antigen 125 (CA 125), and tissue polypeptide antigen (TPA), were measured
      in 26 patients with skeletal metastases and 11 patients with primary malignant
      bone tumors. TPA, which was elevated in 16 patients (61.5%), was the most
      sensitive marker for detection of skeletal metastases. Combined measurement of
      these markers was useful in detecting skeletal metastases from primary lesions,
      although tumor markers had little organ specificity. In addition, skeletal
      metastases could be completely differentiated from primary lesions by the use of
      multivariate discriminant analysis of markers. The most and least powerful
      discriminating factors were AFP and CA 19-9, respectively. On multidimensional
      scaling, the distance between AFP and CEA was longest, with the other markers
      scattered between them. Expression of individual markers can not be linked to
      that of other markers.

PMID- 1370134
TI  - Malignant pilomatricoma. An immunohistochemical study with antihair keratin
      antibody.
AB  - A case is reported of malignant pilomatricoma confirmed by immunohistochemistry
      using anti-human hair keratin (anti-HHK) antibody prepared by the authors. The
      tumor occurred in the soft tissue of the inguinal region of an 88-year-old woman,
      with later invasion of the epidermis. No other possible primary lesion was found
      at autopsy. Histologically, the tumor was squamous cell carcinoma with nests of
      tumor cells and shadow cell-like necrotic cells showing central keratinization
      and focal calcification. Immunohistochemically, the hair keratin was positive in
      this tumor and in benign pilomatricomas exclusively. All other skin lesions and
      various squamous cell carcinomas examined were negative for this antigen. The
      staining patterns of commercial antiepidermal keratin and antiinvolucrin
      antibodies were significantly different from that of anti-HHK in normal skin and
      in these lesions. To the authors' knowledge, this is the first case of malignant
      pilomatricoma tested with anti-HHK staining. Malignant pilomatricoma is generally
      a low-grade malignant tumor, but it can metastasize and be fatal as it was in
      this case.

PMID- 1370135
TI  - Tumor and host response to arginine and branched chain amino acid-enriched total
      parenteral nutrition. A study involving Walker 256 carcinosarcoma-bearing rats.
AB  - The metabolic effects of total parenteral nutrition (TPN) solutions containing
      different profiles of individual amino acids were investigated in the rats
      bearing Walker 256 carcinosarcoma. The rats were subcutaneously inoculated with
      10(7) tumor cells and 6 days later were continuously infused intravenously for 8
      days with three different TPN solutions. The experimental and control solutions
      were composed of high concentrations of branched chain amino acids (BCAA) and
      arginine (high Arg + BCAA TPN), high concentrations of BCAA (high BCAA TPN) and
      regular amino acids (regular TPN), respectively, and were isonitrogenous,
      isocaloric, and isovolemic. Rats receiving subcutaneous injection of saline
      rather than tumor cells received high Arg + BCAA TPN as pair-fed controls. The
      flooding dose method of 14C-leucine was used for the analysis of protein
      synthesis. With the feeding of high Arg + BCAA TPN, the tumor-bearing rats
      revealed a smaller increase of tumor volume and lower tumor fractional rates of
      growth (Kg) and synthesis (Ks) as well as protein synthesis (PS), compared with
      the high BCAA TPN and regular TPN in tumor-bearing rats. There were no
      significant differences of Ks and PS in liver and muscle between TPN groups,
      whereas tumor-bearing rats infused with high Arg + BCAA TPN displayed higher
      levels of whole-body Ks and PS than other TPN groups in tumor-bearing rats and
      pair-fed nontumorous rats. Except for liver RNA content which showed a lower
      level in tumor-bearing rats with high Arg + BCAA TPN, no other differences of DNA
      and RNA contents were found in tumor, liver, and muscle of the different TPN
      groups. The current results indicate that individual amino acids can influence
      tumor growth and protein metabolism, and that arginine, in combination with BCAA,
      may reduce tumor growth through a reduction in protein synthesis.

PMID- 1370136
TI  - Kinetics of restitution of left ventricular relaxation.
AB  - Although the kinetics of cardiac systolic force restitution have been well
      described, the restitution kinetics of left ventricular relaxation have not been
      examined. To define relaxation restitution behavior, we studied seven dogs
      chronically instrumented with left ventricular high-fidelity micromanometers and
      piezoelectric dimension crystals. After a priming period at a basic cycle length
      of 375 msec, test extrastimuli were introduced after a range of extrasystolic
      intervals (ESIs). Relaxation behavior of control and extrasystolic beats was
      characterized by the time constant of isovolumic relaxation, tau. Relaxation
      restitution can be described by two concatenated monoexponential curves, an early
      phase described by a rapid time constant and a late phase described by a slower
      time constant (TC1, 36.21 +/- 7.90 msec; TC2, 75.94 +/- 10.65 msec; p less than
      0.05). The first phase of relaxation restitution parallels systolic force
      restitution over the same range and displays faster recovery (TCs, 58.93 +/-
      10.01 msec, p less than 0.05). Postextrasystolic restitution of test pulses after
      beats at fixed ESIs depends on the initial ESI. Relaxation recovery of
      postextrasystolic beats proceeds faster with smaller initial ESIs (TC1 for ESI of
      300 msec, 13.27 +/- 4.05 msec; TC1 for ESI of 450 msec, 72.85 +/- 21.72 msec; p
      less than 0.0001). The monoexponential pattern of restitution was seen with model
      independent descriptors of relaxation as well as with tau.

PMID- 1370137
TI  - Long-term EEG-video-audio monitoring: computer detection of focal EEG seizure
      patterns.
AB  - Twelve individuals with medically refractory partial seizures had undergone EEG
      video-audio (EVA) monitoring over 1-15 (mean 10.5) days. We selectively
      reexamined available 15-channel EEGs (video-cassettes) totaling 461 h and
      containing 253 EEG focal seizures. Computer analysis (CA) of these bipolar
      records was performed using a mimetic method of seizure detection at 6 successive
      computer settings. We determined the computer parameters at which this method
      correctly detected a reasonably large percentage of seizures (81.42%) while
      generating an acceptable rate of false positive results (5.38/h). These
      parameters were adopted as the default setting for identifying focal EEG seizure
      patterns in all subsequent long-term bipolar scalp and sphenoidal recordings.
      Factors hindering or facilitating automatic seizure identification are discussed.
      It is concluded that on-line computer detection of focal EEG seizure patterns by
      this method offers a satisfactory alternative to and represents a distinct
      improvement over the extremely time consuming and fatiguing off-line fast visual
      review (FVR). Combining CA with seizure signaling (SS) by the patients and other
      observers increased the correct detections to 85.38% CA is best used in
      conjunction with SS.

PMID- 1370138
TI  - EEG coherence as a predictor of spike propagation.
AB  - The relationship between resting EEG coherence and the propagation of spike
      activity from an experimental cortical focus was investigated in 6 rats. EEG was
      collected from an array of 6 epicortical electrodes positioned over the posterior
      hind limb sensorimotor (HL) and frontal (Fr1, Fr2) cortices. Coherence decreased
      non-linearly for all frequency bands with increasing interelectrode distance. The
      greatest decrement in coherence occurred in the region corresponding to the
      junction between hind limb (HL) and frontal (Fr1) cortices. The decrease in
      coherence was greatest for the highest frequency band for all interelectrode
      pairs. A spike focus was induced in all 6 animals following the application of
      bicuculline at the most posterior electrode of the cortical array. In 5 of the 6
      animals spike propagation was delayed at the junction of HL and Fr1 cortices,
      where the greatest decrease in coherence was observed. In one animal spike
      activity never advanced across this region. These results demonstrate an
      association between intracortical coherence and the spatial propagation of spike
      activity. The function of short and long cortico-cortical pathways as mediators
      of both EEG coherence and cortical spike propagation are discussed.

PMID- 1370139
TI  - Partial status epilepticus: short-term prediction of seizure outcome from on-line
      EEG analysis.
AB  - Several combinations of ictal and interictal EEG abnormalities have previously
      been identified in partial status epilepticus (PSE). Some are associated with a
      consistently higher seizure index than others. On-line analysis of the initial
      segments of the EEG monitoring and familiarization with seizure indices
      corresponding to each combination may provide useful clues to rapidly foretell
      short-term seizure recurrence in patients with PSE. Referring to matrices
      reconstructed from an analysis of the initial min of the monitoring in 64
      patients with recorded PSE can help to identify quickly those patterns which are
      most often associated with the highest probability of relapsing seizures.
      Awareness of the probability range of recording additional seizures observed with
      each of these various patterns may provide guidelines for judicious patient
      enrollment and for meaningful assessment of results in prospective studies of
      treatment efficacy in PSE.

PMID- 1370140
TI  - Comparison and correlation of surface and sphenoidal electrodes with simultaneous
      intracranial recording: an interictal study.
AB  - We prospectively compared and correlated interictal spikes recorded with
      simultaneous surface, sphenoidal, depth and subdural electrodes in 21 patients.
      Although the amplitude of sphenoidal spikes was often larger than that of surface
      spikes in patients with mesial basal temporal ictal and interictal foci, only 1
      patient had exclusively sphenoidal spikes. Spikes with maximal amplitude at the
      sphenoidal electrode arose from mesial temporal, temporal neocortical and orbital
      frontal foci. An inferior vertical temporal dipole (hippocampal positive and
      inferior temporal neocortex negative) was associated with surface and sphenoidal
      spikes.

PMID- 1370141
TI  - Detection of neonatal seizures through computerized EEG analysis.
AB  - Neonatal seizures are a symptom of central nervous system disturbances. Neonatal
      seizures may be identified by direct clinical observation by the majority of
      electrographic seizures are clinically silent or subtle. Electrographic seizures
      in the newborn consist of periodic or rhythmic discharges that are distinctively
      different from normal background cerebral activity. Utilizing these differences,
      we have developed a technique to identify electrographic seizure activity. In
      this study, autocorrelation analysis was used to distinguish seizures from
      background electrocerebral activity. Autocorrelation data were scored to quantify
      the periodicity using a newly developed scoring system. This method, Scored
      Autocorrelation Moment (SAM) analysis, successfully distinguished epochs of EEGs
      with seizures from those without (N = 117 epochs, 58 with seizure and 59
      without). SAM analysis showed a sensitivity of 84% and a specificity of 98%. SAM
      analysis of EEG may provide a method for monitoring electrographic seizures in
      high-risk newborns.

PMID- 1370142
TI  - Localization of the sources of EEG delta, theta, alpha and beta frequency bands
      using the FFT dipole approximation.
AB  - FFT dipole approximation and 3-dimensional dipole modelling were used to
      determine the locations of the equivalent dipole model sources of the delta,
      theta, alpha, beta-1 and beta-2 frequency bands in 13 normal subjects during
      resting. From each subject, 2 successive data sets were analysed, each consisting
      of 10 epochs of 2 sec randomly collected during 30 min. ANOVAs showed that over
      subjects, the source locations of EEG frequency bands differed significantly in
      the vertical and antero-posterior dimensions. Results of data set 2 confirmed
      those of data set 1. The source of delta was deepest and most anterior, theta
      more posterior and less deep, alpha most posterior and highest on the vertical
      dimension, beta-1 deeper and slightly more anterior than alpha, and beta-2 again
      more anterior and deeper than beta-1. Thus, the depth of source location was not
      linearly related to temporal frequency. The sources of all 5 bands were oriented
      in the sagittal direction; delta mean fields had steeper gradients anteriorly,
      alpha and beta-1 posteriorly. The power map for any frequency was well described
      by a single phase angle. The results indicate that the different EEG frequency
      bands during a given EEG epoch are generated by neural populations in different
      brain locations.

PMID- 1370143
TI  - Decreased alpha bandwidth responsiveness to photic driving in Alzheimer disease.
AB  - The power spectra of the photically activated occipital EEGs of 9 mildly to
      moderately demented probable Alzheimer disease (AD) patients (according to NINCDS
      ADRDA criteria), 9 normal age-matched control and 27 normal subjects of different
      ages were compared. In normal subjects, photic stimulation with rhythmic flashes
      ranging between 2 and 20 Hz elicited a characteristic response in each EEG
      bandwidth (delta, theta, alpha, beta1 and beta2). The magnitude of each bandwidth
      response was a function of the frequency of the photic stimulus. In AD patients
      the alpha bandwidth response curve was significantly smaller than that of age
      matched controls (MANOVA main effect of group, P = 0.018); all the other
      bandwidth response curves were normal. Therefore, in AD there is a selective
      abnormality in the alpha bandwidth responsiveness to photic stimulation, probably
      due to AD pathology in the neuronal generator of the alpha rhythm.

PMID- 1370144
TI  - Macular dysfunction in multiple sclerosis revealed by steady-state flicker and
      pattern ERGs.
AB  - Recent evidence indicates that the 2nd harmonics of steady-state (8 Hz)
      electroretinograms to either sinusoidal flicker (FERG) or to counterphased
      gratings (PERG) presented in the macular region (9 degrees) represent different
      subsets of generators in the inner retina. We evaluated the steady-state macular
      FERG and PERG 2nd harmonics (2F and 2P, respectively) in 19 normal subjects (19
      eyes) and in 23 multiple sclerosis patients (44 eyes; 25 eyes with a history of
      clinical optic neuritis, and 19 eyes with no history of optic neuritis,
      subclinical eyes). The mean 2F and 2P amplitudes were significantly reduced, as
      compared to controls, in both subclinical and optic neuritis eyes. The 2P phase
      was significantly delayed, as compared to controls, in subclinical eyes, whereas
      2F phase was delayed in eyes with optic neuritis. 2F was outside the 95%
      confidence limits (in amplitude or phase) in 11/19 subclinical eyes and in 25/25
      optic neuritis eyes. 2P was outside the normal range in 12/19 subclinical eyes
      and in 24/25 optic neuritis eyes. These results show that FERG and PERG 2nd
      harmonics are significantly altered in multiple sclerosis eyes with or without a
      clinical history of optic neuritis. This finding suggests a dysfunction of inner
      macular layers which may result from direct retinal involvement or retrograde
      degeneration.

PMID- 1370145
TI  - Electrophysiological evidence of different abilities to form cross-modal
      associations in children with autistic behavior.
AB  - This study evaluates the amplitudes of auditory evoked responses and the
      variability of evoked responses, using a signal-to-noise ratio (SNR) method
      applied to individual evoked potential in a cross-modal (sound and light)
      association paradigm in 17 children with autistic behavior matched for sex and
      chronological age with normal children. Auditory evoked responses were smaller in
      children with autistic behavior than in normal children. The modifications of
      amplitudes and of SNR during cross-modal associations allowed the separation of
      children with autistic behavior into 3 subgroups who presented different patterns
      of ability to form cross-modal associations. These 3 subgroups of children
      presented different clinical profiles demonstrating that the differences observed
      in the ability to form cross-modal associations can be related to differences in
      the main psychophysiological functions such as attention, intention, motility,
      association, contact and communication.

PMID- 1370146
TI  - On the possibility of independent activation of bilateral mismatch negativity
      (MMN) generators.
AB  - Event-related potential (ERP) studies on auditory selective attention have
      suggested that the neuronal traces underlying the mismatch negativity (MMN)
      develop separately for left and right ear inputs. We investigated whether this
      feature of the MMN could be exploited to activate the MMN generators in each
      hemisphere independently. Given the location of the MMN sources, this would allow
      separate assessment of left and right hemisphere auditory cortical structures.
      The MMN was elicited in a dichotic oddball paradigm using stimuli and conditions
      of stimulation that should optimize transmission of left and right ear stimuli to
      the contralateral auditory cortices. The MMN demonstrated no interhemispheric
      asymmetries, indicating that the bilateral MMN generators were symmetrically
      involved. The results of a supplementary experiment provide evidence for the
      simultaneous existence of multiple traces for MMN generation.

PMID- 1370147
TI  - Measurement of interhemispheric time differences in generalised spike-and-wave.
AB  - We have compared interhemispheric time differences (ITD) calculated by
      coherence/phase and linear and non-linear correlation analyses of generalised
      spike-wave episodes in 30 patients (15 with primary generalised epilepsy (PGE), 5
      with secondary generalised epilepsy (SGE) and 10 with a lateralised epileptogenic
      area). Most cases were recorded during routine departmental EEGs. No significant
      difference was found between measures of interhemispheric synchrony (IS)
      (proportion of ITDs that are synchronous) calculated using the linear and the non
      linear correlation techniques, although the latter gave slightly more (average
      7%) valid ITD estimates. This suggests that the non-linear correlation technique
      does not provide significantly more time difference information than its linear
      counterpart. Similarly, no significant differences in IS values were identified
      between the coherence/phase and the correlation techniques. For all 3 techniques,
      IS values greater than 50% were derived for most patients with PGE and SGE; the
      proportion of patients with a lateralised epileptogenic area showing this was
      smaller. However, broad overlap in the distribution of IS values between the 3
      groups suggests that individual patients cannot reliably be distinguished using
      these methods.

PMID- 1370148
TI  - Voluntary acts and readiness potentials.

PMID- 1370149
TI  - Stimulation of lipolysis in cultured fat cells by tumor necrosis factor,
      interleukin-1, and the interferons is blocked by inhibition of prostaglandin
      synthesis.
AB  - Multiple cytokines induce a number of alterations in lipid metabolism which can
      produce hyperlipidemia. Recent studies have demonstrated that tumor necrosis
      factor (TNF) increases lipolysis, resulting in an increase in circulating FFA
      levels, which stimulates hepatic triglyceride production, thereby contributing to
      the hyperlipidemia induced by TNF. In the present investigation we have
      determined the effects of a variety of cytokines on lipolysis in cultured 3T3
      F442A adipocytes. TNF increased lipolysis approximately 3-fold with a maximal
      effect at 100 ng/ml and a half-maximal increase at 5-10 ng/ml. This increase was
      first observed 8 h after incubation with TNF. Interleukin-1 (IL-1) and interferon
      alpha (IFN), -beta, and -gamma also stimulated lipolysis in cultured adipocytes.
      The half-maximal increase in lipolysis occurred at approximately 10 ng/ml IL-1, 5
      ng/ml IFN alpha, 10 ng/ml IFN beta, and 8 ng/ml of IFN gamma. Maximal lipolysis
      was observed at approximately 100 ng/ml for each of these cytokines, with the
      exception of IFN beta, for which maximal stimulation was observed at 1000 ng/ml.
      Neither platelet-activating factor nor IL-6 stimulated lipolysis; therefore, it
      is unlikely that these compounds mediate the increase in lipolysis induced by
      cytokines. However, indomethacin, a well known inhibitor of prostaglandin
      synthesis, prevented the increase in lipolysis induced by TNF, IL-1, IFN alpha,
      IFN beta, or IFN gamma. Indomethacin did not affect basal lipolysis or the acute
      stimulation of lipolysis induced by epinephrine. These results demonstrate that
      multiple cytokines can increase lipolysis and that this increase is mediated by
      cytokine-induced stimulation of prostaglandin synthesis.

PMID- 1370150
TI  - Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting
      cell lines.
AB  - New insulin-secreting cell lines (INS-1 and INS-2) were established from cells
      isolated from an x-ray-induced rat transplantable insulinoma. The continuous
      growth of these cells was found to be dependent on the reducing agent 2
      mercaptoethanol. Removal of this thiol compound caused a 15-fold drop in total
      cellular glutathione levels. These cells proliferated slowly (population doubling
      time about 100 h) and, in general, showed morphological characteristics typical
      of native beta-cells. Most cells stained positive for insulin and did not react
      with antibodies against the other islet hormones. The content of immunoreactive
      insulin was about 8 micrograms/10(6) cells, corresponding to 20% of the native
      beta-cell content. These cells synthesized both proinsulin I and II and displayed
      conversion rates of the two precursor hormones similar to those observed in rat
      islets. However, glucose failed to stimulate the rate of proinsulin biosynthesis.
      In static incubations, glucose stimulated insulin secretion from floating cell
      clusters or from attached cells. Under perifusion conditions, 10 mM but not 1 mM
      glucose enhanced secretion 2.2-fold. In the presence of forskolin and 3-isobutyl
      1-methylxanthine, increase of glucose concentration from 2.8-20 mM caused a 4
      fold enhancement of the rate of secretion. Glucose also depolarized INS-1 cells
      and raised the concentration of cytosolic Ca2+. This suggests that glucose is
      still capable of eliciting part of the ionic events at the plasma membrane, which
      leads to insulin secretion. The structural and functional characteristics of INS
      1 cells remained unchanged over a period of 2 yr (about 80 passages). Although
      INS-2 cells have not been fully characterized, their insulin content was similar
      to that of INS-1 cells and they also remain partially sensitive to glucose as a
      secretagogue. INS-1 cells retain beta-cell surface antigens, as revealed by
      reactivity with the antigangloside monoclonal antibodies R2D6 and A2B5. These
      findings indicate that INS-1 cells have remained stable and retain a high degree
      of differentiation which should make them a suitable model for studying various
      aspects of beta-cell function.

PMID- 1370151
TI  - Effects of continuous infusion of insulin-like growth factor I and II, alone and
      in combination with thyroxine or growth hormone, on the neonatal
      hypophysectomized rat.
AB  - In this study, we examined the effects of systemically administered insulin-like
      growth factor (IGF)-I and -II on growth of the hypophysectomized (Hx) neonatal
      rat. Neonatal Wistar rats were Hx or sham Hx on postnatal day (PND) 6 and
      implanted sc with Alzet pumps on PND 10. Recombinant human IGF-I or -II were
      infused between PND 10 and 18 at an average dose of 1.9 micrograms/g body weight
      (BW) per day. In addition, some groups received daily sc injections of
      recombinant human GH or thyroxine (T4) at 2.5 micrograms and 25 ng/g BW per day,
      respectively. Pups were sacrificed on PND 18 and serum IGF levels determined.
      Despite restoration of serum IGF-I levels to sham control values in the Hx pups
      infused with IGF-I, no significant increase in BW occurred, although some
      increase in individual organ growth was observed (spleen, kidney, lung).
      Similarly, administration of IGF-II proved ineffective as a growth promoter in
      the neonatal Hx rat. In contrast, GH alone stimulated BW gain (P less than
      0.001). T4 proved most potent in increasing skeletal growth (50% increase over Hx
      controls, P less than 0.001), without increasing serum IGF-I or -II levels. IGF-I
      and GH were equally effective in promoting a small yet statistically significant
      (17% over Hx controls, P less than 0.05) increase in skeletal growth. A
      synergistic effect on BW was observed with combined administration of T4 plus IGF
      I to the Hx pups (P less than 0.05). The effects of hormonal therapy on serum IGF
      binding proteins (IGFBPs) was assessed by Western ligand blots. Administration of
      IGF-I, but not GH, resulted in increased levels of IGFBP-3, the predominant IGFBP
      of the adult rat. We conclude that systemically administered IGFs in doses that
      result in normalization of serum levels are ineffective promoters of somatic
      growth in neonatal rats. While normalization of serum IGF-I levels does result in
      modest skeletal growth, selective organ growth and increased serum IGFBP-3,
      growth stimulation does not equal that seen with GH (body weight) or thyroid
      hormone (skeletal growth). Differences in IGFBP profiles fail to account for the
      increased potency of GH as a promoter of BW gain. Thus, our data do not support a
      major endocrine role for IGF-I or -II in neonatal growth, but are consistent with
      an autocrine/paracrine action of IGF in the mediation of neonatal mammalian
      growth.

PMID- 1370152
TI  - Expression and secretion of galanin during pregnancy in the rat.
AB  - The expression of galanin messenger RNA (mRNA) in the pituitary and conceptus of
      pregnant rats has been studied at various stages of gestation. Using Northern
      blot analysis and in situ hybridization we have found that high levels of mRNA
      coding for galanin were detected in the conceptus during early pregnancy. The
      level of expression in conceptuses increased until day 11-12 after which the
      levels decreased rapidly. In contrast, in the pituitary galanin mRNA continued to
      increase throughout pregnancy, especially in the latter half of pregnancy as
      serum estradiol levels has been reported to be increased. The size of the galanin
      transcript was the same in the conceptus and pituitary (0.9 kilobase). Expression
      of this mRNA was confined to the decidua and was first seen at day 5 of pregnancy
      at a time when implantation swellings were first observed. Galanin antisense
      probe hybridized strongly to the decidual cells that surround the implantation
      site. At day 11 of pregnancy the galanin mRNA was found in both the
      antimesometrial and the mesometrial tissue with the highest concentration in the
      region lateral to the antimesometrial cells and continued toward the mesometrial
      cells. Serum galanin levels measured by an RIA using synthetic rat galanin as
      standard and antisera raised against porcine galanin, exhibited a temporal
      pattern similar to the pattern of mRNA expression in decidua, with a 7.1-fold
      increase at day 12 of pregnancy followed by a decline. In summary, decidual cells
      may differentiate into an endocrine cell during pregnancy. The galanin secreted
      by these cells, in addition to acting locally in a paracrine/autocrine fashion,
      may function as a placental hormone with systemic effects on distal target
      tissues.

PMID- 1370153
TI  - Tissue distribution and regulation of insulin-like growth factor (IGF)-binding
      protein-3 messenger ribonucleic acid (mRNA) in the rat: comparison with IGF-I
      mRNA expression.
AB  - Insulin-like growth factor-binding protein-3 (IGFBP-3) is the most abundant IGFBP
      in rat and human sera. The present study demonstrates the expression of the rat
      IGFBP-3 gene in a large number of tissues and coexpression, but not necessarily
      equal expression, with IGF-I mRNA. Tissues with a major abundance of IGFBP-3 were
      kidney, antrum of stomach, placenta, uterus, and liver. Changes in hepatic and
      renal levels of IGFBP-3 mRNA were analyzed after hypophysectomy (with and without
      GH treatment) and in the developing postnatal rat. These results were compared to
      changes in IGF-I mRNA levels under the same physiological conditions. Using S1
      nuclease analysis, IGFBP-3 mRNA was present in the kidney and liver of 1-day-old
      rats and rose significantly in both organs by week 1. Thereafter, levels remained
      relatively constant, particularly in the liver. This is in marked contrast to the
      hepatic IGF-I pattern, which showed a continual rise up to 8 weeks. Hepatic IGFBP
      3 gene expression was partially GH dependent, with IGFBP-3 mRNA levels falling
      (approximately 50%) after hypophysectomy and rising slightly after GH treatment.
      These changes were much less dramatic than those in IGF-I mRNA. In contrast, the
      renal levels of IGFBP-3 mRNA increased after hypophysectomy, (approximately
      100%), but did not decrease with GH treatment. These data suggest that IGFBP-3
      mRNA abundance is regulated differently in different tissues, and in at least
      some tissues is less sensitive to regulation than is IGF-I mRNA.

PMID- 1370154
TI  - Expression of GLUT1 and GLUT2 glucose transporter isoforms in rat islets of
      Langerhans and their regulation by glucose.
AB  - Previous studies revealed that rat islets express the GLUT2-liver facilitative
      glucose transporter isoform, a glucose carrier with a low affinity for glucose
      but a high capacity for glucose transport. These studies indicated the presence
      of a second glucose transporter in rat islets; however, they did not indicate to
      which of the five known facilitative glucose transporters it corresponded. In
      this study, we isolated RNA from rat islets of Langerhans and confirmed the
      presence of GLUT2 mRNA. In addition, we present data indicating that the second
      isoform expressed in islets is the GLUT1-erythrocyte isoform. The effect of
      culturing islets in 5.5, 8.3, or 11.1 mM glucose on the levels of GLUT1 and GLUT2
      mRNA also was examined. The levels of GLUT1 and GLUT2 mRNA were two- and
      threefold higher, respectively, in islets cultured for 24 h in 11.1 mM glucose
      compared with those incubated in the presence of 5.5 mM glucose. Therefore, the
      previously observed increase in GLUT2 mRNA levels in the islets of rats made
      hyperglycemic by chronic infusion of glucose can be mimicked in vitro, implying
      that glucose regulates GLUT2 mRNA expression.

PMID- 1370156
TI  - Intrahepatic up-regulated expression of extracellular matrix protein receptors in
      chronic active hepatitis type B.
AB  - The aim of the present study was to investigate the differences in expression of
      beta 1 integrins between normal liver and the inflamed livers of patients with
      chronic active hepatitis B. Immunohistochemical staining with monoclonal
      antibodies that specifically recognize the common beta 1 chain and five different
      alpha subunits has been performed in frozen liver biopsy sections from 10
      patients with chronic active hepatitis B and from 4 patients with normal livers.
      The major findings of our study were de novo expression in liver with chronic
      active hepatitis B of alpha 2 and alpha 3 subunits on both periportal hepatocytes
      and on lobular hepatocytes in close proximity to lymphocyte infiltrates. These
      results indicate the existence of an up-regulatory process in the expression of
      beta 1 integrins, especially the alpha 2 and alpha 3 subunits, in the inflamed
      liver tissue from patients with chronic active hepatitis B, suggesting that these
      integrins could play an important role in the development of liver fibrosis and
      in regulating intrahepatic lymphocyte migration.

PMID- 1370155
TI  - Sequence of human galanin and its inhibition of glucose-stimulated insulin
      secretion from RIN cells.
AB  - Human progalanin cDNA was cloned with polymerase chain reaction techniques. The
      cDNA sequence predicts that the human form of galanin has a substitution of the
      glycine residue found at position 30 in other species and thus is likely to
      retain this residue during posttranslational processing and not be amidated at
      the COOH terminus. Furthermore, the cDNA sequence predicts three additional amino
      acid substitutions compared with known galanins. Human galanin was synthesized,
      and its bioactivity was compared with porcine and rat galanin based on inhibition
      of insulin release from a glucose-responsive rat insulinoma (RIN) cell line.
      Human galanin inhibited glucose-stimulated insulin secretion in a dose-dependent
      manner in RIN cells. Human, porcine, and rat galanin exhibited similar activity
      with ED50 less than 1 nM.

PMID- 1370157
TI  - Immunohistochemical demonstration of galaninlike immunoreactive nerves in the
      human pancreas.
AB  - Galanin, the newly discovered 29 amino acid-residue peptide, has been shown to
      suppress glucose-induced insulin secretion in experimental animals, but its
      presence and physiological role in the human pancreas have not been established.
      In this study, the occurrence and distribution of galanin immunoreactivity in the
      human pancreas was investigated by immunohistochemistry. In addition, the
      possible coexistence of galanin and vasoactive intestinal peptide
      immunoreactivity in neural elements of the pancreas was examined. In the human
      pancreas, galanin immunoreactivity was localized in numerous nerve fibers around
      glandular acini, ductules and blood vessels, and in a few nerve fibers within
      islets. Nerve cells with galanin immunoreactivity were frequently noticed.
      Immunostainings for galanin and for vasoactive intestinal peptide on serial
      adjacent sections of intrapancreatic ganglia showed the coexistence of the two
      immunoreactivities in a large proportion (73.3%) of nerve cells. These
      observations may provide a morphological basis for the possible neurotransmitter
      or neuromodulator role of galanin in the human pancreas.

PMID- 1370158
TI  - Ultrastructural localization of somatostatin- and substance P-immunoreactive
      nerve fibers in the feline liver.
AB  - The distribution and the possible source of somatostatin- and substance P
      immunoreactive nerve fibers were studied in the liver of the cat by
      immunocytochemical techniques. Abundant substance P-immunoreactive and a moderate
      number of somatostatin-immunoreactive nerve fibers were found running around the
      blood vessels in the perilobular connective tissue. Some somatostatin
      immunoreactive nerve cell bodies were also observed in the liver. A moderate
      number of somatostatin-immunoreactive nerve profiles were found inside the
      hepatic lobules along the sinusoid endothelial cells and the hepatocytes. The
      interspace between the axon and hepatocyte and endothelial cells membranes was
      about 20 nm. Cutting the extrinsic hepatic nerves resulted in marked reduction of
      substance P-immunoreactive nerves but only a slight reduction of somatostatin
      immunoreactive nerves in the liver. These findings provide a morphological basis
      for the possibility that somatostatin and substance P may act as transmitters or
      neuromodulators on the neighboring smooth muscle cells of vessels and may
      regulate the function of the hepatocytes. It is also possible that some of these
      fibers serve sensory function along the blood vessels.

PMID- 1370159
TI  - Gastrin is a potent stimulant of the parietal cell--maybe.

PMID- 1370160
TI  - Tachykinin antagonists inhibit nerve-mediated contractions in the circular muscle
      of the human ileum. Involvement of neurokinin-2 receptors.
AB  - The effects of some newly developed tachykinin antagonists that are selective for
      the neurokinin (NK)-1 (L 668,169) or the NK-2 (MEN 10,207, L 659,877 and R 396)
      tachykinin receptor on the cholinergic and noncholinergic contraction and on the
      nonadrenergic noncholinergic relaxation produced by electrical field stimulation
      (50 Hz) were investigated in mucosa-free circular strips of the human ileum. The
      strips were contracted by substance P and neurokinin A as well as by selective NK
      2-receptor ligands, [beta Ala8]neurokinin A(4-10), and MDL 28,564, the latter
      peptide being capable of discriminating between NK-2-receptor subtypes. The
      selectivity of the antagonists for NK-1 or NK-2 receptors was confirmed in
      pharmacological experiments using substance P, neurokinin A, and [beta
      Ala8]neurokinin A(4-10) as stimulants. Among the NK-2-selective antagonists, MEN
      10,207 displayed the highest affinity, followed by L 659,877 and R 396. The
      antagonists MEN 10,207 and L 659,877 inhibited the noncholinergic contraction to
      electrical stimulation in a concentration-dependent manner; L 668,169 and R 396
      were poorly effective. Thus the potency of antagonists toward the noncholinergic
      response closely paralleled their rank order of potency at NK-2 receptors. The
      cholinergic contraction and nonadrenergic noncholinergic relaxation were not
      inhibited by the antagonists. Both substance P- and neurokinin A-like
      immunoreactivities were detected in extracts of the human ileum, and the identity
      of the corresponding peptides was confirmed by reverse-phase high-performance
      liquid chromatography. It was concluded that in addition to NK-1 receptors, the
      circular muscle of the human ileum also contains NK-2 receptors. Activation of
      the latter is chiefly responsible for the noncholinergic contraction to nerve
      stimulation.

PMID- 1370161
TI  - Detection of hepatitis C virus RNA in serum of patients with chronic hepatitis C
      treated with interferon-alpha.
AB  - We tested serial serum samples for hepatitis C virus RNA from patients undergoing
      treatment for chronic hepatitis C with interferon-alpha using an assay that
      combined reverse transcription and polymerase chain reaction. The subjects
      studied were 20 patients with chronic hepatitis who had serum antibody to
      hepatitis C virus (anti-C100-3). Before therapy, hepatitis C virus RNA was
      detected in 18 (90%) and 20 (100%) patients using primer sets derived from the
      NS3 region or the 5'-noncoding region of hepatitis C virus, respectively.
      Hepatitis C virus RNA became undetectable in all patients whose ALT level fell
      into the normal range during therapy. However, hepatitis C virus RNA reappeared
      in all patients whose ALT levels rose again after therapy, usually before the
      relapse. In patients whose ALT levels did not become normal, hepatitis C virus
      RNA did not disappear during therapy. Thus therapy with interferon-alpha appears
      to be beneficial in chronic hepatitis C because of its suppressive effects on
      hepatitis C virus replication. Detection of hepatitis C virus RNA in serum is
      useful for evaluating the antiviral effect of interferon.

PMID- 1370162
TI  - D-penicillamine prevents the development of hepatitis in Long-Evans Cinnamon rats
      with abnormal copper metabolism.
AB  - The Long-Evans Cinnamon rat is a mutant strain that contracts hereditary
      hepatitis and, eventually, spontaneous hepatocellular carcinoma. Because we found
      a corresponding gross copper accumulation in the liver of the rats, we examined
      whether the development of hepatitis in our rat system could be prevented by
      administration of D-penicillamine. D-Penicillamine is a copper-chelating agent
      and one of the drugs effective for human Wilson's disease, in which abnormal
      copper metabolism is also observed. The results show that D-penicillamine
      treatment inhibited the elevation of serum transaminases, suppressed abnormal
      histological changes in the liver and completely prevented the onset of hepatitis
      in the Long-Evans Cinnamon rats. We further found that the copper concentration
      in the liver and serum copper and ceruloplasmin levels were decreased, whereas
      the urinary copper level was increased in the D-penicillamine-treated Long-Evans
      Cinnamon rats. These findings demonstrate that the pathogenesis of hereditary
      hepatitis in Long-Evans Cinnamon rats is due to abnormal copper accumulation in
      the liver.

PMID- 1370163
TI  - Insulin-like growth factor-binding protein-3 is functionally normal in pregnancy
      serum.
AB  - Insulin-like growth factor-binding protein-3 (IGFBP-3) carries most of the serum
      IGFs as a 150K ternary complex which increases during pregnancy. However, recent
      studies have demonstrated that IGFBP-3 is absent in pregnancy serum when measured
      by ligand blotting after electrophoresis. In the present study we demonstrate
      that, by several criteria, IGFBP-3 appears functionally intact in pregnancy
      serum. Serum samples were collected from pregnant women between 2-40 weeks
      gestation. Serum immunoreactive IGFBP-3 and acid-labile (alpha) subunit increased
      linearly throughout pregnancy. Ligand blotting confirmed diminution of IGFBP-3 at
      2 weeks gestation and complete absence after 4 weeks gestation or when
      nonpregnancy serum was preincubated with amniotic fluid. When less harsh methods
      (neutral chromatography or transient acidification) were used, IGFBP-3 appeared
      functionally normal in pregnancy serum. Fractionation of pregnancy serum by
      Superose-12 gel permeation chromatography showed similar elution profiles for
      both IGFBP-3 and alpha-subunit compared to those for nonpregnancy serum.
      Preincubation of nonpregnancy serum with pregnancy serum or amniotic fluid had no
      effect on IGFBP-3 recovery. After acidification and neutralization of serum to
      destroy endogenous alpha-subunit, ternary complex formation, measured by
      radiolabeled alpha-subunit binding, was essentially identical in all nonpregnancy
      and pregnancy serum, except for a slight loss of activity in first trimester
      serum. Since the 150K complex cannot form unless IGFBP-3 binds IGFs and alpha
      subunit normally, these results suggest that IGFBP-3 in native pregnancy serum is
      functionally normal.

PMID- 1370164
TI  - The 24/25-kDa serum insulin-like growth factor-binding protein is increased in
      elderly women with hip and spine fractures.
AB  - Fractures of the hip in elderly women represent a clinical syndrome (age-related
      osteoporosis) often marked by decreased calcium absorption and secondary
      hyperparathyroidism. We studied 13 elderly women with fractures of the hip and
      spine and 18 healthy similarly aged control women to determine whether serum
      insulin-like growth factor-I (IGF-I) or its carrier binding proteins (IGFBPs)
      were altered in this syndrome. Serum IGF-I concentrations were not different in
      the two groups (P = 0.50), but immunoreactive PTH was significantly higher in the
      fracture group (58.50 +/- 8.20 vs. 13.50 +/- 2.70 ng/L; P less than 0.003).
      Binding of [125I]IGF-I to IGFBP-3, IGFBP-2, and IGFBP-1, measured by ligand
      blotting, was not statistically different in the 2 groups, but binding
      intensities for the serum 24/25-kDa IGFBP were approximately 2.5 times greater in
      fracture women than control women (P less than 0.0005). In data pooled from both
      groups, PTH correlated strongly (r = 0.70; P less than 0.0001) with the relative
      binding intensities for the 24/25-kDa IGFBP. Based on previous work, we speculate
      that production of the 24/25-kDa IGFBP, which in vitro is known to inhibit IGF-I-
      and IGF-II-mediated osteoblast function, may be stimulated by PTH in patients
      with the syndrome of age-related osteoporosis.

PMID- 1370165
TI  - The insulin-like growth factor (IGF)-binding proteins and IGF bioactivity in
      Laron-type dwarfism.
AB  - Laron-type dwarfism (LTD) is caused by a variable defect in the GH receptor gene
      and is, therefore, an ideal model to study the physiology of the insulin-like
      growth factors (IGFs) and their binding proteins (IGFBPs) in the complete absence
      of GH action. In this study we examined the overnight variation of the IGFs,
      IGFBPs, and IGF bioactivity in two prepubertal subjects with LTD. Subject 1 was a
      14-yr-old female, 103 cm tall (-8.3 SD), and subject 2 was a 11.5-yr-old male,
      103.6 cm tall (-5.9 SD). Both had serum IGF-I levels below 0.07 U/mL and low
      constant serum IGF-II levels overnight (185 +/- 10 and 232 +/- 8 micrograms/L),
      despite high serum GH levels [mean GH, 65 (32.5 micrograms/L) and 53 mU/L (26.5
      micrograms/L)]. Serum IGFBP-1 levels increased overnight (from 24 and 22
      micrograms/L at 2000 h to 83 and 110 micrograms/L at 0800 h) as serum insulin
      levels fell [from 19 (136 pmol/L) and 17 mU/L (122 pmol/L) at 2000 h to less than
      2 (less than 14 pmol/L) and 5 mU/L (36 pmol/L) at 0800 h] in subjects 1 and 2,
      respectively. Serum IGFBP-2 levels remained constant overnight, as assessed on
      Western Ligand blotting and, despite the changes in IGFBP-1, remained the most
      prominent IGFBP throughout. On size separation, most of the IGF-II (greater than
      60%) eluted with IGFBP-2 and the other low mol wt IGFBPs. Serum IGFBP-3 levels
      were reduced, and IGFBP-3 was not the major IGF carrier in LTD serum, in contrast
      to normal serum. An IGFBP-3-specific protease that was heat sensitive and cation
      dependent was identified as the cause of an apparent overnight rise of serum
      IGFBP-3 levels. No IGFBP-3 variation and no proteolytic activity was seen in
      normal serum or rapidly separated LTD plasma. Serum IGF bioactivity, measured in
      a porcine cartilage bioassay, was 0.18 and 0.55 U/mL in subjects 1 and 2;
      differences in bioactivity between subjects did not relate to serum IGF-II
      levels, but, rather, to differences in IGFBP-3 levels. Serum IGF bioactivity was
      not constant overnight and varied in a similar fashion in both subjects 1 and 2,
      with reduction in bioactivity between 0600-0800 h by 55% and 32%, suggesting the
      presence of inhibitory factors in the LTD serum; this decrease coincided with the
      rise in serum IGFBP-1 levels.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1370166
TI  - Differential expression of aminopeptidase-N on human ovarian granulosa and theca
      cells.
AB  - The expression of aminopeptidase-N and neutral endopeptidase in human ovarian
      tissue was examined using specific monoclonal antibodies for each of these
      peptidases and histochemical staining for enzyme activity. Aminopeptidase-N is a
      membrane-bound metalloprotease catalyzing the removal of N-terminal amino acids
      from peptides and was detected by immunofluorescence staining on theca interna
      cells in secondary follicles and on luteinized thecal cells in preovulatory
      follicles and corpora lutea. However, aminopeptidase-N was not detected on
      granulosa cells. Peptidase activity was also detected by histochemical staining
      on theca interna cells and luteinized thecal cells. Luteinized granulosa cells
      showed peptidase activity, despite the lack of aminopeptidase-N. Neutral
      endopeptidase was not detected in ovarian granulosa and thecal cells. These
      observations indicate that aminopeptidase-N can be a useful surface marker for
      thecal cells.

PMID- 1370167
TI  - Regulation of human basophil activation. II. Histamine release is potentiated by
      K+ efflux and inhibited by Na+ influx.
AB  - Na+ and K+ are the major extra- and intracellular cations, respectively. We have
      thus studied the role of these ions on human basophil histamine release by
      modifying their transmembrane gradients or by increasing membrane ion fluxes
      using ionophores. 1) When external Na+ (reduced to 4 mM) was replaced by the
      nonpermeating Na+ substitute N-methyl-D-glucamine, the release of histamine was
      enhanced in 2 mM Ca2+ (from 37.5 +/- 8.0% in 140 mM Na+ to 68.5 +/- 9.1% in low
      Na+) and became possible in the presence of low Ca2+ (at 1 microM Ca2+: from 0.6
      +/- 0.7% in 140 mM Na+ to 36.2 +/- 8.0% in low Na+); moreover, in low Na+, the
      release of histamine became partly independent on Ca2+ influx. 2) Increasing the
      Na+ influx with the cation channel-forming gramicidin D inhibited the release of
      histamine by 33.2 +/- 13.6% (n = 6) in an external Na(+)-dependent manner. 3)
      Decreasing K+ efflux using K+ channel blockers (4-aminopyridine, quinine,
      sparteine) inhibited histamine release in a dose-response manner. 4) The K+
      ionophore valinomycin, which increases K+ efflux, slightly enhanced IgE-mediated
      histamine release when used alone, whereas it potentiated the release of
      histamine from leukocytes previously treated with 4-aminopyridine by 57.0 +/-
      18.6% (n = 7). 5) Decreasing K+ efflux by increasing external K+ inhibited IgE
      mediated release in a similar manner as Na+ did. The inhibitory effects of Na+
      and high K+ were not additive, thus suggesting that both cations inhibited the
      release by a common mechanism. In conclusion 1) our data evidence that histamine
      release from human basophils is inhibited by Na+ influx and potentiated by K+
      efflux; 2) they suggest that K+ channels are present on the basophil membrane and
      that Na+ and K+ fluxes act on histamine release most probably via modulation of
      membrane potential.

PMID- 1370168
TI  - Expression of variable exon A-, B-, and C-specific CD45 determinants on
      peripheral and thymic T cell populations.
AB  - A mAb (I/24) has been generated that is specific for a determinant on mouse CD45
      molecules. Reactivity of this mAb with a panel of CD45 transfected cell lines
      demonstrated that the determinant recognized is dependent upon expression of one
      or more CD45 variable exons and that exon C is sufficient for its expression. The
      exon C-specific epitope detected by I/24 is expressed at high density on
      essentially all B lymphocytes and at an intermediate density on the vast majority
      of CD8+ splenic T cells. Two distinct subpopulations of CD4+ splenic T cells were
      detected, a minor subpopulation that expresses this exon determinant at high
      density and a major subpopulation that expresses it at a much lower density. This
      first identification of a CD45RC-specific reagent allowed a comparison of the
      expression of exon A-, exon B-, and exon C-specific determinants on peripheral
      and thymic lymphoid populations. When splenic lymphocytes were analyzed for
      expression of CD45RA (reactive with mAb 14.8), CD45RB (reactive with mAb 23G2 or
      mAb 16.A), and CD45RC (reactive with mAb I/24) determinants, it was found that
      each of these CD45 determinants had a distinct pattern of expression on CD4+ and
      CD8+ T cells and B cells. CD45RB and RC epitopes were also detected at high
      density on a small proportion (0.7 to 4.1%) of thymocytes. Both CD45RB and RC
      epitopes were found predominantly on CD4-CD8- and CD4-CD8+ thymocytes but were
      also found on small numbers of CD4+CD8+ and CD4+CD8- cells. The population of
      thymocytes that expressed CD45RB and CD45RC determinants displayed a novel TCR
      CD3 phenotype characterized by a level of expression that was intermediate
      between that seen in the larger CD3 bright and CD3 dull populations of
      thymocytes.

PMID- 1370169
TI  - Stimulation of human T lymphocytes by Leishmania lipophosphoglycan-associated
      proteins.
AB  - Lipophosphoglycan (LPG) is a glycoconjugate present on the surface of Leishmania
      promastigotes that has been reported to promote intracellular survival of these
      parasites, to protect mice against leishmaniasis, and to elicit T cell responses
      in infected mice and humans. We investigated whether LPG and its components could
      elicit proliferative responses and cytokine secretion from leishmaniasis patient
      PBMC. LPG prepared by standard methods (LPG-1) stimulated patients T cells to
      proliferate and secrete IFN-gamma. LPG was fractionated into several components.
      An LPG-1-specific T cell line was shown to respond to the core region but not to
      the repeating saccharide units. LPG-1 was fractionated to yield an LPG-free-
      associated protein complex and an LPG-2 fraction that was more than 95% depleted
      of associated protein. The ability of LPG-2 to stimulate T cells was
      significantly decreased over that of LPG-1. In contrast, LPG-AP stimulated T cell
      proliferation and IFN-gamma production. Therefore, proteins associated with LPG
      were effective in eliciting patient T cell responses, whereas the glycolipid
      enriched moiety was weakly effective or ineffective at stimulating these
      responses.

PMID- 1370170
TI  - Epitopes on the outer surface protein A of Borrelia burgdorferi recognized by
      antibodies and T cells of patients with Lyme disease.
AB  - We have characterized immunogenic epitopes of the 31-kDa outer surface protein A
      (OspA) protein of Borrelia burgdorferi, which is a major surface Ag of the
      spirochete causing Lyme disease. Full length and truncated forms of rOspA
      proteins were expressed in Escherichia coli, and their reactivities with
      antibodies and human T cell clones isolated from patients with Lyme disease were
      determined. The epitopes recognized by three of four OspA-reactive T cell clones
      are contained within the 60 COOH-terminal amino acids. Each of the four OspA
      reactive T cell clones has a different HLA class II molecule involved in Ag
      recognition and recognizes a distinct epitope. One T cell clone promiscuously
      recognized an epitope in the context of different HLA-DQ molecules. In addition,
      the binding of a murine monoclonal anti-OspA antibody, as well as antibodies in
      sera of three of five patients with Lyme disease, was dependent upon the amino
      acids in the carboxy-terminal protion of this protein. Taken together, our
      results indicate that the 60 COOH-terminal amino acids of OspA contain epitopes
      recognized by human antibodies and T cells.

PMID- 1370171
TI  - Molecular cloning of a cDNA encoding CD34, a sialomucin of human hematopoietic
      stem cells.
AB  - CD34 is a 115-kDa transmembrane glycoprotein of unknown function that is
      expressed on human hematopoietic progenitor cells and the small vessel
      endothelium of a variety of tissues. We have isolated a CD34 cDNA clone from a KG
      1 cell library following three rounds of transient expression in COS cells and
      enrichment by panning with the anti-CD34 mAb MY10 and BI-3C5. The 5' and 3' ends
      of the full-length cDNA were subsequently amplified by polymerase chain reaction
      from KG-1 RNA; the final cDNA clone contained 2615 bp and ended in a poly(A)
      tail. COS cells transfected with the cDNA clone expressed a surface protein of
      approximately 110 kDa that was immunoprecipitated by MY10. Southern blot analysis
      suggested that CD34 is a single copy gene. A 2.7-kb CD34 transcript was observed
      in the hematopoietic cell lines KG-1, KMT-2, AML-1, RPMI 8402, and MOLT 13 and
      the endothelial cells BAE and EAhy926, but not in monocytes, resting T cells, or
      the cell lines Laz 509, HL-60, U937, K562, and HeLa. The cDNA sequence predicts a
      40-kDa type I integral membrane protein with nine potential N-linked and numerous
      potential O-linked glycosylation sites in its extracellular domain. There are two
      consensus protein kinase C phosphorylation sites and one potential tyrosine
      kinase phosphorylation site in the cytoplasmic portion of CD34. CD34 has no
      significant sequence homology to any known protein but has some structural
      similarities to the heavily glycosylated leukocyte surface molecule CD43.

PMID- 1370172
TI  - Neutrophil migration across monolayers of resting or cytokine-activated
      endothelial cells. Role of intracellular calcium changes and fusion of specific
      granules with the plasma membrane.
AB  - Chemoattractants, used at concentrations to invoke optimal neutrophil chemotaxis,
      induce rapid changes in neutrophils such as a transient increase in intracellular
      Ca2+ ([Ca2+]i). We have previously observed that neutrophils adhering to cytokine
      activated endothelial cells (EC) also respond with a rapid rise in [Ca2+]i caused
      by an endothelial membrane-bound form of platelet-activating factor. After
      preloading with the intracellular Ca(2+)-chelator bis-(O-aminophenoxyl)ethane
      N,N,N',N'-tetraacetic acid (BAPTA/AM), neutrophils were no longer able to respond
      with a rapid rise in [Ca2+]i toward the chemoattractant FMLP or to rIL-1 beta
      pretreated EC. These neutrophils were still able to adhere and migrate under the
      conditions tested. The only difference was that the BAPTA/AM-treated neutrophils
      migrated a little slower than untreated control neutrophils. This discrepancy was
      not observed at later time points. The BAPTA/AM-preloaded neutrophils did not
      differ from unloaded neutrophils in actin polymerization responses. Whereas
      untreated neutrophils demonstrated an up-regulation of the specific granule
      markers CD11b, CD45, and CD67 during migration (without any release from the
      azurophil granules), the BAPTA/AM pretreatment completely prevented this process.
      The BAPTA/AM-preloaded neutrophils did not release vitamin B12-binding protein
      from the specific granules upon treatment with FMLP. The down-modulation of the
      selectin member LAM-1, as seen upon neutrophil activation, was not affected by
      BAPTA/AM pretreatment of the neutrophils. Thus, neither the rapid rise in [Ca2+]i
      nor specific granule fusion with the plasma membrane constitute a prerequisite
      for neutrophil migration across resting or cytokine-activated EC.

PMID- 1370173
TI  - Human dermal microvascular endothelial but not human umbilical vein endothelial
      cells express CD36 in vivo and in vitro.
AB  - CD36 is an 88-kDa glycoprotein that has been identified on platelets, monocytes,
      and some endothelial cells. Experimental evidence suggests that CD36 mediates the
      binding of Plasmodium falciparum-infected RBC to a variety of cells, and
      therefore may play a role in the vascular complications associated with malaria.
      Additionally, CD36 may also bind the extracellular matrix proteins thrombospondin
      and collagen. Human umbilical vein endothelial cells have been used in in vitro
      models examining the binding of P. falciparum RBC to endothelial cells, but they
      do not consistently express cell surface CD36. Inasmuch as human dermal
      microvascular endothelial cells (HDMEC) differ in a variety of ways from large
      vessel endothelial cells, we have examined HDMEC for cell surface expression of
      CD36 in vivo and in vitro. Direct immunofluorescence of skin showed bright
      staining of HDMEC with antibody recognizing CD36 and flow cytometric analysis of
      cultured HDMEC revealed cell surface expression. In contrast, large vessel
      endothelial cells were not stained with antibody recognizing CD36 in vivo and
      cultured cells derived from umbilical vein failed to express cell surface CD36 in
      vitro. Western immunoblots of lysates of HDMEC but not human umbilical vein
      endothelial cells demonstrated an 88-kDa protein that comigrated with CD36 from
      platelets. Functional studies demonstrated that adherence of PRBC to HDMEC was
      inhibited up to 66% by mAb recognizing CD36. Furthermore, the expression of CD36
      on HDMEC was increased in a dose- and time-dependent manner by IFN-gamma, and was
      decreased by protein kinase C agonists. These data demonstrate that HDMEC express
      functionally active CD36 and this expression can be positively and negatively
      regulated by soluble factors. This study demonstrates that HDMEC are useful in
      the study of CD36-mediated binding of PRBC to endothelial cells in vitro and
      provides further evidence of distinct phenotypic differences between HDMEC and
      large vessel endothelial cells.

PMID- 1370174
TI  - Ordered appearance of zidovudine resistance mutations during treatment of 18
      human immunodeficiency virus-positive subjects.
AB  - The order of appearance in the reverse transcriptase gene of four mutations
      implicated in the development of resistance to zidovudine was investigated by
      selective polymerase chain reaction. Serial human immunodeficiency virus isolates
      were studied from 18 initially asymptomatic individuals who had been treated with
      zidovudine for 2 years. Most subjects had similar patterns. The first mutation
      occurred transiently at codon 70; its disappearance was paralleled by the
      appearance of a mutation at codon 215. Subsequently, in some individuals, the
      mutation at codon 70 reappeared. During the 2 years of treatment, no mutations
      developed at codon 219 and only one at codon 67, suggesting that most individuals
      developed only partly resistant virus. This was confirmed by plaque-reduction
      assay. Six subjects progressed to AIDS within the 2-year study period, confirming
      that the development of highly resistant isolates is not required for progression
      in treated individuals. No clear temporal relationship was found between the
      development of partial resistance and progression.

PMID- 1370176
TI  - Chemotherapy for nonmetastatic osteogenic sarcoma: the Memorial Sloan-Kettering
      experience.
AB  - PURPOSE: Adjuvant chemotherapy improves disease-free survival (DFS) for patients
      with osteogenic sarcoma (OS). We reviewed our experience with OS to determine
      prognostic factors, the role of preoperative chemotherapy and subsequent
      histologic response, and the role of salvage chemotherapy after poor initial
      response. METHODS: From 1975 to 1984, we saw 279 patients with previously
      untreated OS without metastasis. All patients received intensive chemotherapy and
      underwent surgical resection of primary tumor. Chemotherapy included high-dose
      methotrexate; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH); and
      bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also
      received cisplatin. RESULTS: DFS was not affected by use of preoperative
      chemotherapy versus immediate surgery, by use of limb-sparing surgery versus
      amputation, age, sex, or dose intensity of chemotherapy. DFS did correlate with
      serum lactate dehydrogenase (LDH), alkaline phosphatase, primary tumor site,
      race, and histologic response to preoperative chemotherapy. There was no
      difference in DFS for patients with a poor histologic response who did or did not
      receive cisplatin, although patients who did receive cisplatin had a longer time
      to relapse. The 5-year DFS was 76% for patients aged less than or equal to 21
      years who had extremity primary tumor and were treated with the T10 protocol.
      CONCLUSIONS: Intensive chemotherapy can achieve DFS for a high proportion of
      patients with OS. Although it is a powerful predictor of DFS, histologic response
      to preoperative chemotherapy cannot be assessed at diagnosis. We have not shown
      an ability to salvage patients with an unfavorable response. We need to increase
      the proportion of patients with a favorable response, identify the patients who
      will have an unfavorable response, and develop novel treatments to salvage poor
      responders.

PMID- 1370175
TI  - A comparison of the variable antigens expressed by clone IV-1 and subgroup III of
      Neisseria meningitidis serogroup A.
AB  - Serogroup A Neisseria meningitidis of subgroup III has caused two pandemics of
      meningococcal meningitis since 1966 and recently spread to East Africa. The last
      epidemics in West Africa in the early 1980s were caused by clone IV-1. Surface
      antigens of clone IV-1 strains from West Africa and subgroup III strains from
      both pandemic waves were analyzed. Lipopolysaccharide was stable within clone IV
      1 but variable in subgroup III. Pili from clone IV-1 possessed class I epitopes,
      while those from subgroup III also possessed class IIa epitopes. Certain class 5
      protein variants were expressed by both bacterial clones, possibly reflecting
      either inheritance of primeval genes or horizontal transmission. Exposure of
      Gambians to clone IV-1 bacteria stimulated production of bactericidal antibodies
      cross-reactive with subgroup III bacteria in some individuals but of type
      specific antibodies in others. Gambians without bactericidal antibodies usually
      became healthy carriers rather than developing meningococcal disease on exposure
      to virulent meningococci.

PMID- 1370177
TI  - Effects of free and bound insulin-like growth factors on proteoglycan metabolism
      in articular cartilage explants.
AB  - This article describes the effects of bound forms of insulin-like growth factors
      (IGFs) on proteoglycan metabolism by bovine articular cartilage in explant
      culture. When these growth factors were added to articular cartilage explants
      complexed with their native serum binding proteins (BPs), both IGF-I-BP complex
      and IGF-II-BP complex stimulated proteoglycan synthesis to different degrees over
      a 3-day period. When added to the medium of cultures of articular cartilage over
      5 days, IGF-II-BP complex induced high rates of synthesis and low rates of
      catabolism of proteoglycans, giving rise to tissue levels of proteoglycan similar
      to those observed in fresh tissue. When articular cartilage was maintained in
      culture with the same concentration of IGF-I-BP complex, tissue levels of
      proteoglycans fell over the culture period because of lower rates of proteoglycan
      synthesis. Analysis of the proteoglycans synthesized by articular cartilage in
      the presence of free or bound IGF-I or IGF-II showed that these growth factors
      stimulated the rate of synthesis of the large proteoglycan species present in
      cartilage but did not affect the synthesis of the small proteoglycans.

PMID- 1370178
TI  - S-100 protein immunostaining identifies cells expressing a chondrocytic phenotype
      during articular cartilage repair.
AB  - The healing of articular surface defects has been studied with conventional
      histology, which relies on the staining of the extracellular matrix to identify
      the phenotype of the cells present. A chondrospecific cellular marker would be
      useful. S-100 protein has been found in all chondroid tissues studied, and we
      evaluated its usefulness in the study of articular cartilage repair. Full
      thickness rabbit femoral condylar defects were made, and the specimens were
      studied at serial time intervals. S-100 protein staining positively showed
      chondroid cells in the 7- and 14-day specimens, which were not identifiable by
      conventional techniques. At 30 and 60 days, an S-100 positive band of cells
      separated a deep safranin-O positive hypertrophic layer from a fibrocellular
      surface layer. At 120 days, the presence of S-100 protein identified cells with
      chondrogenic potential, and the lack of S-100 protein in other cells embedded in
      conventionally stained matrix suggested that these cells were no longer of a
      chondroid phenotype. The presence of S-100 protein-identified chondroid cells
      early in the repair process when the cells had not begun to synthesize
      conventionally stainable matrix and the lack of S-100 protein in cells late in
      the repair positively identified a phenotypic change earlier than conventional
      histology.

PMID- 1370179
TI  - Rabbit knee immobilization: bone remodeling precedes cartilage degradation.
AB  - This study analyzed processes underlying osteoporosis and osteoarthrosis after
      short-term immobilization of the right hind limb of postadolescent (2.8 kg) and
      mature (4.0 kg) rabbits. After 3 weeks, the lateral posterior aspect of the
      lateral tibial plateau and the lateral femoral condyle of the immobilized limb
      exhibited prominent subchondral vascular eruptions. Femoral metaphyseal bone
      density decreased 27 and 18% in the immobilized limbs of postadolescent and
      mature rabbits, respectively. Calcein green fluorescence increased 1.9-fold (p
      less than 0.001) in the metaphyseal trabeculae of immobilized femurs. With
      immobilization, sulfate incorporation into femoral cartilage glycosaminoglycan
      increased, although total cartilage glycosaminoglycan and hydroxyproline levels
      were unchanged. Thymidine incorporation into DNA increased four- to fivefold in
      tibial and femoral cartilage of the immobilized limb. In this study, bone loss
      and remodeling preceded erosive cartilage degradation.

PMID- 1370180
TI  - G-CSF for fever and neutropenia induced by chemotherapy.

PMID- 1370181
TI  - G-CSF for fever and neutropenia induced by chemotherapy.

PMID- 1370182
TI  - G-CSF for fever and neutropenia induced by chemotherapy.

PMID- 1370183
TI  - G-CSF for fever and neutropenia induced by chemotherapy.

PMID- 1370184
TI  - The Anser System.

PMID- 1370185
TI  - The Denver II: a major revision and restandardization of the Denver Developmental
      Screening Test.
AB  - Since the Denver Developmental Screening Test was first published 23 years ago,
      it has been utilized worldwide and restandardized in more than a dozen countries.
      Concerns raised through the years by test users about specific items and features
      of the Denver Developmental Screening Test, coupled with a need for more current
      norms, have prompted a major revision and restandardization of the test. For the
      revision, 336 potential items were administered to more than 2000 children. The
      average number of times each item was administered was 540. Using regression
      analysis, composite norms for the total sample and norms for subgroups (based on
      gender, ethnicity, maternal education, and place of residence), were used to
      determine new age norms. The final selection of the 125 Denver II items was based
      on the following criteria: ease of administration and scoring, item appeal to
      child and examiner, item test-retest and inter-rater reliability, minimal
      "refusal" scores, minimal "no opportunity" scores, minimal subgroup differences,
      and a smooth step-like progression of ages at which 90% of children could perform
      the tasks. The major differences between the Denver II and the Denver
      Developmental Screening Test are: 1) an 86% increase in language items; 2) two
      articulation items; 3) a new age scale; 4) a new category of item interpretation
      to identify milder delays; 6) a behavior rating scale; and 7) new training
      materials.

PMID- 1370186
TI  - Participation by pediatricians in early intervention: impetus from Public Law 99
      457.
AB  - Part H of the Individuals with Disabilities Education Act (originally enacted as
      Public Law 99-457) requires that participating states phase in a system of early
      intervention services by 1993. By recognizing the importance of good health in
      the development of infants and toddlers, Congress acknowledged the key role of
      medical care providers in a comprehensive program for young children with or at
      risk for developmental delay or dysfunction. National and state surveys of
      pediatricians suggest limited but growing awareness of this legislation and
      uncertainty about how they might participate effectively. A chief concern relates
      to mechanisms of payment for developmental screening and assessment as well as
      time-demands for participation in interdisciplinary team activities. The American
      Academy of Pediatrics and its state chapters are responding to requests for
      information with educational seminars and print materials. Pediatricians can
      enhance the quality of community support services for children with special needs
      by participating in planning efforts and by coordinating health care with other
      aspects of early intervention. Other professionals and parents are looking to
      pediatricians for leadership and willing participation in the implementation of
      PL 99-457.

PMID- 1370187
TI  - Differential effects of dichlorodiphenyltrichloroethane analogs, chlordecone, and
      2,3,7,8-tetrachlorodibenzo-p-dioxin on establishment of pregnancy in the
      hypophysectomized rat.
AB  - Many of the organochlorine pesticides have been shown to elicit estrogenic
      responses in laboratory animals. Two estrogenic actions, initiation of
      implantation and maintenance of pregnancy, were examined in progesterone-primed,
      delayed-implanting, hypophysectomized rats exposed to several polychlorinated
      hydrocarbons. The insecticide P,P'-dichlorodiphenyltrichloroethane (DDT) was
      nearly devoid of estrogenic activity for initiating implantation, as was a
      dichloro analog, 1,1-dichloro-2-[p-chlorophenyl],2-[o-chlorophenyl]ethane (O,P'
      DDD), but another such analog, 1,1-dichloro-2-(p-chlorophenyl),2-(o
      chlorophenyl)ethylene (O,P'-DDE), was nearly as estrogenic as the O,P'-DDT isomer
      of DDT and the methoxylated analog methoxychlor. The latter three compounds not
      only initiated implantation, but maintained pregnancy when given in large (200
      mg/kg) and repeated doses. Another insecticide, chlordecone (Kepone) was more
      estrogenic than any of the DDT analogs and maintained pregnancy with a single
      dose of 50 mg/kg. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a toxic contaminant
      of herbicide production, did not induce implantation at a dose of 125
      micrograms/kg, but inhibited the implantation initiated by estrone in 35% of the
      animals. The mechanism of this antiestrogenicity is unknown but most probably
      does not involve direct action via the classical estrogen receptor. The possible
      interference with the normal blastocyst-uterine interactions of these
      polychlorinated xenobiotics may be an important factor in their being considered
      reproductive toxins.

PMID- 1370188
TI  - Effectiveness of India ink as a long-term colonic mucosal marker.
AB  - We prospectively studied the use of India ink as a long-term or "permanent"
      mucosal marker as part of a study investigating the natural history of diminutive
      distal colorectal polyps. Twenty-six patients had 32 India ink tatoos implanted.
      The tatoo sites of the 19 patients who were followed at least 6 months continued
      to display intensely stained mucosa at the original sites. No side effects or
      complications were encountered. India ink appears to be a safe and effective long
      term marker for colonic mucosal lesions.

PMID- 1370189
TI  - Morphometric comparisons of optic nerve axon loss in acquired immunodeficiency
      syndrome.
AB  - Axonal degeneration and diminution of the axonal population in the optic nerve
      have been documented in aging and in various neuro-ophthalmic conditions. We
      applied morphometric techniques to the postmortem examination of optic nerves
      obtained from patients with acquired immunodeficiency syndrome. Twelve optic
      nerves (eight from patients with AIDS and four from age-matched control eyes)
      were stained with paraphenylenediamine and morphometrically analyzed with a
      computer-assisted image and measurement system. Degeneration was often severe and
      was scattered throughout all of the AIDS-affected optic nerves. In the AIDS
      affected optic nerves, the mean axonal population was markedly lower than the
      mean obtained from normal optic nerves (880,000 vs 1,507,000). Despite the
      approximate 40% loss of axons, mean axonal diameters were not markedly different,
      suggesting that no particular class of axon was especially susceptible to AIDS
      associated degeneration. The extent and pattern of axonal loss in optic nerves of
      patients with AIDS suggest that the changes may not only be secondary to damage
      at the retina, but may reflect an AIDS-associated primary optic neuropathy.

PMID- 1370190
TI  - Crystalloids in angiomyolipoma. 1. A previously unnoticed phenomenon of renal
      angiomyolipoma occurring at a high frequency.
AB  - We present a description of unique crystalloids in renal angiomyolipoma that have
      not previously been reported. The crystalloids cannot be identified by
      hematoxylin-and-eosin staining. Detailed observation after diastase treatment
      followed by PAS staining revealed needle- and rod-like crystalloids, which were
      clearly seen even by light microscopy, in 11 of 17 patients. Their appearance was
      characterized by the following phenomena: (a) They appeared mainly in large
      epithelioid smooth-muscle cells; (b) they appeared at a relatively high frequency
      at sites where smooth-muscle cells showed diffuse proliferation and where a
      hemangiopericytic pattern was observed; (c) they were often detected easily even
      at a site with a sarcomatous appearance; and (d) PAS-positive, diastase-resistant
      granules were often observed by light microscopy in the vicinity of crystalloids
      in all 17 patients. Electron-microscopic observation of one patient also revealed
      characteristic crystalloids. Prior to our study, only one patient had been
      reported to show crystalloids by electron microscopy, and the crystalloids were
      interpreted as renin. However, our study used Bowie's staining and
      immunohistochemistry to prove they were not renin. The nature of the crystalloids
      still needs to be elucidated. The fact that they closely resemble structures seen
      in alveolar soft part sarcoma provides one clue to their identification.

PMID- 1370191
TI  - Bile duct adenomas with endocrine component. Immunohistochemical study and
      comparison with conventional bile duct adenomas.
AB  - Bile duct adenomas are small nodules that are usually found incidentally on the
      liver surface at abdominal surgery or autopsy. We recently analyzed two such
      lesions that, in addition to the typical small caliber ducts, contained
      periductular nests and clusters of uniform round cells, suggestive of endocrine
      cell proliferation. Follow-up of these patients did not show endocrine tumors
      elsewhere. The lesions were studied by immunohistochemistry (avidin-biotin
      peroxidase technique) and compared with conventional bile duct adenomas (seven
      cases). The results showed these cells to decorate with several endocrine
      markers, namely, neuron-specific enolase, chromogranin, synaptophysin, and Leu-7.
      Endocrine markers were not seen in the cells of conventional bile duct adenomas.
      Epithelial markers, that is, cytokeratin (CAM 5.2 antibody) and epithelial
      membrane antigen, were expressed by the cells composing both conventional bile
      duct adenomas and those with endocrine-like cells, although with less intensity
      in the endocrine cell clusters. We suggest that some bile duct adenomas contain
      endocrine cell proliferations that morphologically may resemble a small carcinoid
      tumor or the so-called pulmonary tumorlet. Neurosecretory granules have
      previously been identified in some cholangiocarcinomas and in bile duct
      proliferation associated with cholestasis. The endocrine clusters in biliary
      adenomas may constitute a diagnostic pitfall and must be separated from
      metastases of carcinoids or islet cell tumors.

PMID- 1370192
TI  - Routine diagnosis of mammary Paget's disease. A modern approach.
AB  - This study compares the diagnostic reliability of conventional mucin
      histochemistry and immunocytochemical techniques in distinguishing mammary
      Paget's disease from superficial spreading malignant melanoma and primary
      intraepidermal carcinoma. Formalin-fixed, paraffin-embedded archival tissue was
      used and comprised 13 cases of mammary Paget's disease, five cases of superficial
      spreading melanoma, and six cases of intraepidermal carcinoma. Sections from each
      case were stained for the presence of mucin using diastase periodic-acid-Schiff
      (d-PAS) with and without an alcian blue counterstain as well as
      immunocytochemistry for cytokeratin (CAM 5.2), epithelial membrane antigen (NCRC
      11) and c-erb B-2 (21N). Mucin staining in intraepidermal carcinoma and malignant
      melanoma was consistently negative. Diastase-resistant PAS positivity was seen in
      six of 13 cases of mammary Paget's disease and eight of 13 cases using an alcian
      blue counterstain. NCRC-11 showed positive immunoreactivity in four of six cases
      of intraepidermal carcinoma, one in five cases of melanoma, and five of 13 cases
      of mammary Paget's disease. Positive immunoreactivity using CAM 5.2 and 21N was
      seen in all cases of mammary Paget's disease, with consistent negative
      immunoreactivity in the other tumor types. We conclude that CAM 5.2 and 21N
      should be used in the investigation of mammary Paget's disease in preference to
      conventional mucin stains.

PMID- 1370193
TI  - Paneth cell-like change of the prostate gland. A histological,
      immunohistochemical, and electron microscopic study.
AB  - Paneth cell-like change (PCLC) of the prostatic glandular epithelium was focally
      observed in one case of normal glandular epithelium, two cases of glandular and
      stromal hyperplasia, one case of prostatic intraepithelial neoplasia, and four
      cases of prostatic adenocarcinoma. The distinctive cells were characterized by
      bright, eosinophilic cytoplasmic granules on routine hematoxylin and eosin
      stained material. The cytoplasmic granules in the benign prostatic epithelium
      were periodate-Schiff's procedure (PAS)-positive and diastase resistant and
      immunohistochemically negative for lysozyme, neuron-specific enolase,
      chromogranin, and serotonin. The eosinophilic granules in the prostatic
      intraepithelial neoplasia and adenocarcinoma cases were immunohistochemically
      positive for chromogranin, serotonin, and neuron-specific enolase, and negative
      for lysozyme. By electron microscopy the eosinophilic granules represented
      exocrine-like or lysosomal-like vesicles in the benign epithelium and neuro
      endocrine granules in the malignant epithelium. The lesion represents a prostatic
      epithelial PCLC rather than a Paneth cell metaplasia. PCLC is the common
      histological manifestation of two different phenomena: (a) a PAS-positive and
      diastase-resistant eosinophilic cytoplasmic granular change in benign prostatic
      epithelium, and (b) endocrine differentiation with neuroendocrine granules in
      dysplastic and malignant prostatic epithelia. The importance of recognizing PCLC
      lies in its differentiation from other possible prostatic cytoplasmic inclusions.

PMID- 1370194
TI  - A 30-s PAS stain for frozen sections.
AB  - A modified periodate-Schiff's procedure technique for application in frozen
      section diagnosis is described. This simplified reaction performed using a
      microwave-oven procedure takes only 30 s and is useful in demonstrating mucin as
      well as mucin-containing cells. We found that this method facilitates frozen
      section diagnosis.

PMID- 1370195
TI  - Hyperamylasemia and hematologic malignancies.

PMID- 1370196
TI  - Primary lung cancer producing alpha-fetoprotein.
AB  - Reports of alpha-fetoprotein-producing lung tumors are rare. Only 24 such
      patients with these tumors have been previously studied. We report the case of a
      patient with a large cell carcinoma of the lung and a serum alpha-fetoprotein
      level of 9,300 ng/mL, with no evidence of hepatic or other systemic
      abnormalities. Serum levels of alpha-fetoprotein returned to normal
      postoperatively.

PMID- 1370197
TI  - Cerebrospinal fluid neurochemistry in children and adolescents with obsessive
      compulsive disorder.
AB  - Cerebrospinal fluid hormones, monoaminergic metabolites, and dynorphin A (1-8
      sequence) were examined in 43 children with severe, primary obsessive-compulsive
      disorder. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid were
      positively correlated with one of eight obsessive-compulsive disorder severity
      ratings and three of seven measures of improvement following 5 weeks of treatment
      with clomipramine hydrochloride. Arginine vasopressin concentration was
      significantly and negatively correlated with several ratings of obsessive
      compulsive disorder symptom severity, while oxytocin concentration was positively
      correlated with depressive symptoms. The ratio of arginine vasopressin to
      oxytocin was also negatively correlated with obsessive-compulsive disorder and
      depressive symptoms. Comorbid affective disorder was associated with decreased
      arginine vasopressin concentrations, while concomitant anxiety disorder was
      associated with increased oxytocin. Dynorphin A (1-8 sequence), homovanillic
      acid, corticotropin, 3-methoxy-4-hydroxyphenylglycol, and corticotropin releasing
      hormone were not significantly related to obsessive-compulsive disorder symptoms.
      These results seem to indicate that arginine vasopressin may be related to
      obsessive-compulsive disorder symptom severity, while 5-hydroxyindoleacetic acid
      might be associated with drug response.

PMID- 1370198
TI  - Abnormalities in the regulation of vasopressin and corticotropin releasing factor
      secretion in obsessive-compulsive disorder.
AB  - In light of prior data that the central administration of vasopressin in animals
      is associated with abnormal persistence of behaviors acquired under aversive
      conditioning, we studied the secretion of arginine vasopressin into the
      cerebrospinal fluid and plasma in patients with obsessive-compulsive disorder and
      controls. Patients with obsessive-compulsive disorder had significantly elevated
      basal levels of arginine vasopressin in the cerebrospinal fluid and significantly
      increased secretion of arginine vasopressin into the plasma in response to
      hypertonic saline administration. Moreover, seven of 12 patients with obsessive
      compulsive disorder showed a loss of the normal linear relationship between
      plasma arginine vasopressin level and osmolality. In addition, cerebrospinal
      fluid corticotropin releasing hormone, which has synergistic effects with
      arginine vasopressin centrally and at the pituitary gland, was also significantly
      elevated in patients with obsessive-compulsive disorder compared with controls.

PMID- 1370199
TI  - Acute-phase proteins in patients with head and neck cancer treated with
      interleukin 2/interferon alfa.
AB  - Circulating acute-phase proteins may mediate adverse reactions in patients
      receiving biologic response modifiers, including inhibition of immune
      responsiveness and clinical toxic effects. Nine patients with unresectable head
      and neck squamous cell carcinoma were prospectively examined for levels of acute
      phase proteins during interleukin 2/interferon alfa immunotherapy and for
      clinical toxic effects. Simultaneous determination of the in vitro
      immunomodulatory capacity of autologous serum on the induction of lymphokine
      activated killer cells was assessed in 4-hour chromium release assays. Of the
      seven acute-phase proteins analyzed, haptoglobin and C-reactive protein levels
      were elevated before therapy was started. Toxic events leading to cessation of
      interleukin 2/interferon alfa therapy had a high correlation with elevated C
      reactive protein and lowered C3 component of complement levels. No relationship
      was noted between serum levels of acute-phase proteins and induction inhibition
      of lymphokine-activated killer cell cytotoxicity. The role of C-reactive protein
      and complement degradation products in mediating interleukin 2/interferon alfa
      toxicity requires further investigation.

PMID- 1370200
TI  - Histochemical and immunohistochemical characteristics of mast cells in nasal
      polyps.
AB  - In surgically excised nasal polyps, most epithelial mast cells were formalin
      sensitive, chloroacetate esterase (CAE) negative, and chymase negative. Thus,
      this represents a population of mast cells not identified by staining for CAE. On
      the other hand, most stromal mast cells were formalin resistant and CAE positive,
      and although there was some polyp-to-polyp variability in their content of
      neutral protease, most of these cells were positive for both tryptase and
      chymase. The percentage of metachromatic cells in the epithelium and the number
      of metachromatic cells per unit area of polyp tissue did not correlate with an
      index of allergy skin test reactivity or the serum IgE concentration. The
      percentage of mast cells surrounded by pericellular tryptase, suggesting
      activation/degranulation, was significantly higher in the stroma than in the
      epithelium. The findings demonstrate differences between the stroma and the
      epithelium in phenotype and state of activation of mast cells; these are
      postulated to be due to distinct microenvironmental factors that affect mast
      cells at these sites.

PMID- 1370201
TI  - Adhesion molecules on freshly recovered T leukemias promote tumor-directed
      lympholysis.
AB  - Besides facilitating cell to cell adhesion, the molecular interactions between
      CD2 and its ligand CD58 (lymphocyte function-associated antigen-3 [LFA-3]), as
      well as between CD11a/18 (LFA-1) and CD54 (intercellular adhesion molecule-1)
      have recently been recognized to participate in lymphocyte activation,
      recirculation, and effector function, including cytolytic activity towards tumor
      cells. We have investigated the role of CD2/CD58 and CD11a/18/CD54 interactions
      in cellular immune responses directed towards freshly recovered human T-cell
      leukemias. The data support the notion that downregulation of CD54 and CD58
      correlates with enhanced numbers of blasts in circulation and unsusceptibility to
      killing by autologous cytotoxic lymphocytes. Importantly, after induction of CD54
      and CD58 expression on leukemic cells by recombinant cytokines such as tumor
      necrosis factor-alpha, tumor cells become highly susceptible to lymphocyte
      mediated lysis in vitro. Our findings, therefore, stress the point that
      successful immunotherapy of malignant disease may be facilitated by influencing
      not only the immune response itself, but also adhesion molecules on the malignant
      tumor targets.

PMID- 1370202
TI  - Factor-dependent erythroid cell lines derived from mice transplanted with
      hematopoietic cells expressing the v-src oncogene.
AB  - Transplantation of spleen cells from primary reconstituted mice expressing the v
      src oncogene to secondary and tertiary irradiated recipients resulted in the
      emergence of erythroid precursors with a transformed phenotype. When cultured in
      methyl cellulose, these precursors generated colonies of undifferentiated cells
      that could be expanded into continuously growing factor-dependent cell lines in
      liquid culture. All lines tested had a similar phenotype and expressed the v-src
      oncogene. In addition they responded to factors that regulate normal erythroid
      development, namely erythropoietin (Epo), interleukin-3 (IL-3), and mast cell
      growth factor (MGF), the ligand to the c-kit encoded receptor. When cells from
      one of the lines were maintained in the absence of factor, a "factor independent"
      subpopulation emerged that appeared to grow in an autocrine fashion. Conditioned
      medium from these cells stimulated their own growth as well as the growth of
      broad spectrum of normal precursors. Studies with neutralizing antibodies
      indicated that the predominant colony-stimulating factor produced by these cells
      is IL-3.

PMID- 1370203
TI  - Primary myelodysplastic syndromes: diagnostic and prognostic significance of
      immunohistochemical assessment of bone marrow biopsies.
AB  - Material from 63 cases with primary myelodysplastic syndromes (P-MDS) (French
      American-British [FAB] types: refractory anemia [RA] = 21; RA with ring
      sideroblasts [RARS] = 8; RA with excess of blasts (RAEB) = 10; RAEB in
      transformation (RAEBt) = 6; chronic myelomonocytic leukemia [CMML] = 10 and
      unclassifiable = 8, ie, bone marrow aspiration was inadequate and stringent FAB
      criteria were not applicable) was analyzed for bone marrow histologic and
      immunohistochemical patterns. Standard Giemsa, hematoxylin and eosin (H&E) and
      reticulin stains were used for morphologic assessment. To identify the cell
      lineage precisely, chloroacetate esterase staining and an indirect
      immunoperoxidase technique using mouse monoclonal antibodies CD15, CD68, HLA-DR,
      and rabbit polyclonal CD3 and UEA-1 (lectin) was developed on formalin-fixed
      paraffin embedded bone marrow biopsies (BMB). The immunohistochemical assessment
      permitted accurate identification of dysplastic features such as mononuclear and
      binuclear megakaryocytes, Pelger-Huet neutrophils, and binuclear erythroblasts.
      Additional bone marrow histologic and immunohistochemical features observed were
      heterogeneity of immunohistochemical staining in various cell lineages,
      megakaryocytic emperipolesis, alteration of bone marrow microarchitecture,
      intravascular clusters of hematopoietic cells, and the types of benign lymphoid
      aggregates. The nature of abnormally localized immature precursors (ALIP) was
      discerned. Three types of clusters of immature cells were found that were
      difficult to distinguish on Giemsa and H&E morphology, these were erythroid
      aggregates (n = 18); megakaryocytic aggregates (n = 4), and immature granulocytic
      and monocytic aggregates (n = 32). The bone marrow histologic and
      immunohistologic patterns permitted the identification of four groups of clinical
      relevance: Group 1, cases with predominant erythroid hyperplasia and without ALIP
      (n = 15); group 2, cases with prominent myeloid hyperplasia and presence of ALIP
      (n = 32); group 3, cases with hypoplastic MDS (n = 10); and group 4, cases with
      hyperfibrotic MDS (n = 6). Statistical analysis showed a significant difference
      in survival and leukemic transformation between groups 1, 2, 3, and 4, with cases
      in group 2 showing the worst prognosis with early death due to increased
      propensity to leukemic transformation and cytopenia-related complications (P less
      than .0001). We conclude that immunohistochemistry is feasible on routinely
      processed BMB and the information obtained is of diagnostic and prognostic
      importance in P-MDS. The phenotype of ALIP varies with the morphologic and
      histologic subtypes of MDS and the term should be reserved for cases in whom the
      clusters in the intertrabecular region are of myeloid (granulocytic and
      monocytic) lineage on immunohistochemistry.

PMID- 1370204
TI  - Follicular non-Hodgkin's lymphoma cell adhesion to normal germinal centers and
      neoplastic follicles involves very late antigen-4 and vascular cell adhesion
      molecule-1.
AB  - Follicular lymphomas recapitulate the architecture of germinal centers (GCs) of
      normal secondary lymphoid follicles. Using an in vitro binding assay, it has
      recently been demonstrated that the normal B lymphocytes bind to GCs. This
      interaction is mediated by a receptor-ligand pair consisting of the beta 1
      integrin very late antigen 4 (VLA-4) on the B cell, and the vascular cell
      adhesion molecule-1 (VCAM-1) expressed on follicular dendritic cells (FDC).
      Considering the similarities between follicular lymphomas and normal GCs, the
      adhesive interaction of follicular non-Hodgkin's lymphoma (NHL) cells and GCs was
      examined. Cells isolated from 16 of 24 cases of follicular NHL bound to normal
      GCs. Neoplastic follicles could similarly support the binding of follicular NHL
      cells. This adhesion was inhibited by monoclonal antibodies (MoAbs) directed
      against VLA-4 and VCAM-1. This supports the hypothesis that the neoplastic
      follicles used the identical adhesive interactions responsible, at least in part,
      for the localization of normal B cells to GCs. Adhesion receptors have an
      important role in the regulation of normal lymphoid cell proliferation,
      differentiation, and localization. Therefore, an understanding of the adhesive
      interaction of follicular NHL cells with GCs may provide insight into the
      clinical and biologic behavior of these diseases.

PMID- 1370206
TI  - Human lymphokine activated killer (LAK) cells suppress generation of allospecific
      cytotoxic T cells: implications for use of LAK cells to prevent graft-versus-host
      disease in allogeneic bone marrow transplantation.
AB  - We have found that murine lymphokine activated killer (LAK) cells have veto and
      natural suppressor activities in vitro, and prevent graft-versus-host disease
      (GVHD) in vivo. To determine whether human LAK cells mediate veto and natural
      suppression we measured their ability to inhibit generation of allospecific
      cytotoxic T cells (CTL) in mixed lymphocyte culture (MLC). When added to MLCs at
      low concentrations LAK cells caused veto-type inhibition: stimulator-type LAK
      cells inhibited generation of CTL but responder or third-party LAK cells did not.
      At higher concentrations LAK cells caused nonspecific inhibition: all three LAK
      cell types inhibited generation of CTL. LAK cell veto and natural suppressor
      activities were largely eliminated by irradiation with 30 Gy and by depletion of
      CD56+ cells, but increased after depletion of CD3+ cells. LAK cell veto activity
      is not likely an artifact of cold-target inhibition by the LAK cells themselves
      or by proliferation of T cells contaminating LAK cell preparations: (1) veto only
      occurred when LAK cells were added to MLC on days 0 through 2, but not when added
      on day 5; (2) addition of saturating numbers of labeled targets to fixed numbers
      of allo-CTL effectors failed to overcome the inhibitory effects of adding
      stimulator-type LAK cells at the onset of MLC; and (3) CD3-depleted LAK cells
      showed greater veto activity than threefold greater numbers of control LAK cells.
      In light of our previous findings in mice, the current results imply that
      adoptive immunotherapy with LAK cells may be useful in preventing GVHD in human
      bone marrow transplant recipients.

PMID- 1370205
TI  - Absence of abnormalities of c-kit or its ligand in two patients with Diamond
      Blackfan anemia.
AB  - As Diamond-Blackfan anemia shares clinical features with W and Steel defects in
      mice, we investigated the possibility that this human disorder might result from
      an abnormality of the c-kit receptor or its ligand, stem cell factor (SCF). For
      these studies, full nucleotide sequences for coding regions of c-kit and SCF were
      generated for two Diamond-Blackfan anemia patients and were normal. Similarly,
      the kds of SCF receptors on their marrow cells (31 pmol/L, 43 pmol/L) were
      comparable with those found in three normal controls (50 pmol/L, 55 pmol/L, 27
      pmol/L). Serum SCF concentrations were 6.9 ng/mL in patient A, 14.6 ng/mL in
      patient B, who has been in hematologic remission since adolescence, and 2.7 ng/mL
      in the 3-year-old daughter of patient B, who also has Diamond-Blackfan anemia but
      is transfusion-dependent. It is possible that the SCF level in patient B
      increased with puberty, leading to her remission. These data provide evidence
      that Diamond-Blackfan anemia does not result from structural abnormalities of c
      kit or SCF.

PMID- 1370207
TI  - Localization of the platelet-specific HPA-2 (Ko) alloantigens on the N-terminal
      globular fragment of platelet glycoprotein Ib alpha.
AB  - The human platelet-specific alloantigens HPA-2a and HPA-2b (= Kob and Koa)
      together constitute a biallelic antigen system. The HPA-2 antigens have not, to
      date, been located on a particular platelet membrane molecule. Here, we describe
      the localization of these antigens on platelet glycoprotein (GP) Ib alpha.
      Platelets from two patients with the Bernard-Soulier syndrome (BSS) were HPA-2(a
      ,b-) in the immunofluorescence test with HPA-2 alloantibodies on chloroquine
      treated platelets. With monoclonal antibody (MoAb) immobilization of platelet
      antigen assay (MAIPA), positive reactions were obtained only when MoAbs against
      the platelet GPIb/IX complex were used in combination with anti-HPA-2a or -2b
      alloantibodies and normal donor platelets. By immunoprecipitation under
      nonreducing and reducing conditions a protein of 160 Kd and 145 Kd, respectively,
      was precipitated by the anti-HPA-2a serum. A protein migrating identically to
      this was precipitated by anti-GPIb MoAb. Normal donor platelets became HPA-2(a-,b
      ) after elastase treatment, suggesting that anti-HPA-2 antibodies bind to the N
      terminal elastase-sensitive part of GPIb alpha. Anti-HPA-2a antibodies inhibited
      the ristocetin-induced agglutination of HPA-2a-positive platelets but not of HPA
      2a-negative platelets, indicating that the epitopes recognized by these
      alloantibodies are localized in the proximity of the von Willebrand-factor
      binding domain. Together, these data provide evidence that the HPA-2 alloantigens
      are located on the N-terminal globular elastase-sensitive part of GPIb alpha.
      Furthermore, we show that the recently described Siba antigen is probably
      identical to HPA-2a.

PMID- 1370209
TI  - Recombinant rat stem cell factor stimulates the amplification and differentiation
      of fractionated mouse stem cell populations.
AB  - The role of recombinant rat stem cell factor (rrSCF) was studied on defined
      primitive bone marrow cell populations. In agar culture of 500 lineage
      negative/Sca-1-positive (Lin-/Sca-1+) cells, rrSCF alone stimulates small
      colonies of predominantly granulocytic cells. The combinations of rrSCF plus
      interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF),
      or macrophage CSF (CSF-1) stimulated primitive progenitor cells defined as high
      proliferative potential colony-forming cells (HPP-CFC). Synergistic increases in
      total colony numbers were obtained with rrSCF plus GM-CSF, granulocyte CSF (G
      CSF), CSF-1, or IL-6, but not IL-1 or IL-3. Lin-/Sca-1+ cells were incubated in
      liquid culture at 3,000 cells/mL for 6 days in the presence of rrSCF alone or in
      combination with other growth factors. The total number of cells was increased
      twofold in the presence of rrSCF, with the progeny primarily myeloid in nature.
      The greatest increase in cell number was obtained with rrSCF plus IL-3, where the
      cell number increased 40-fold. These factors also stimulated an increase in HPP
      CFC (10-fold) and GM-CFC (500-fold). To determine if these interactions were
      direct, single Lin-/Sca-1+ cells were sorted into microtiter wells and the cell
      proliferation scored 6 days later. RrSCF synergized with IL-3, IL-6, and G-CSF to
      stimulate the proliferation of single cells. The cells in positive wells were
      subcultured into colony-forming assays and up to 400 CFC per well were obtained
      after 14 days incubation of the secondary cultures. These data demonstrate that
      rrSCF acts in combination with various growth factors to directly stimulate the
      amplification potential of hematopoietic primitive precursors, resulting in
      differentiation of these precursors.

PMID- 1370208
TI  - Glucocorticoids downregulate gene expression of GM-CSF, NAP-1/IL-8, and IL-6, but
      not of M-CSF in human fibroblasts.
AB  - Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF),
      macrophage-CSF (M-CSF), neutrophil-activating peptide-1/interleukin-8 (NAP-1/IL
      8), and interleukin-6 (IL-6) are pivotal in the regulation of hematopoiesis and
      immune responses. In mesenchymal cells, their expression is induced by tumor
      necrosis factor alpha (TNF) and other agents. We now show that, while induction
      of cytokine expression by TNF in human lung fibroblasts was parallel,
      glucocorticoid hormones differentially affected their production. Dexamethasone
      (1 mumol/L) concordantly repressed expression of GM-CSF, NAP-1/IL-8 and IL-6. RNA
      and protein levels were reduced to approximately 5%, 20%, and 30% of control
      cells, respectively, as determined by Northern blot analyses and immunoassays. A
      50% reduction of RNA levels for all three cytokines occurred in the range of 1
      hour. In contrast, dexamethasone (1 mumol/L) did not decrease M-CSF RNA levels
      and protein release. M-CSF RNA and protein levels were maintained even when
      dexamethasone (1 mumol/L) was present for the whole duration of a 48-hour TNF
      stimulation. Further experiments showed that dexamethasone downregulates
      expression of GM-CSF, NAP-1/IL-8, and IL-6 mainly by decreasing the mRNA
      stability of these cytokines, and that the dexamethasone-mediated repression of
      cytokine expression depends on ongoing protein and RNA syntheses. Our study
      suggests that glucocorticoid hormones repress expression of a set of cytokine
      genes important in conditions of stress. However, they seem not to affect M-CSF
      expression, which is likely to be more crucial in maintaining long-term functions
      of myeloid cells.

PMID- 1370210
TI  - A unique factor XIII inhibitor to a fibrin-binding site on factor XIIIA.
AB  - An 81-year-old woman, who presented with sudden episodes of spontaneous bleeding,
      was found to have a specific inhibitor of factor XIII. Her fibrin clots had
      approximately 70% gamma-gamma and no alpha polymer formation, under conditions
      where normal fibrin was fully cross-linked; the patient's clots were soluble in
      urea or monochloroacetic acid. Factor XIII activity in her plasma was 24%,
      measured by the dansylcadaverine incorporation assay. When mixed with normal
      plasma, the patient's plasma inhibited fibrin cross-linking; however, in mixtures
      of patient and normal plasma, there was no inhibition of factor XIII activity
      when assayed by the incorporation of dansylcadaverine into casein. Thus, this
      inhibitor was active against fibrin cross-linking but not against ligation of
      small molecules to casein. Consequently, gel electrophoresis of reduced, sodium
      dodecyl sulfate-solubilized fibrin clots was a simple, quantitative method that
      was used to measure inhibitor activity. This inhibitor is unique and has been
      designated inhibitor New Haven. It was neutralized by anti-IgG and anti-kappa. It
      did not inhibit the activation of factor XIII but did inhibit fibrin cross
      linking. There was complex formation between the inhibitor and activated factor
      XIII (A', A*) but not between A2 or fibrinogen. Only A', A* and the 56-Kd
      fragment bound to affinity columns made with this IgG. The inhibitor
      significantly decreased the binding of A', A* to fibrin clots. These data
      indicate that the epitope for this inhibitor is in a fibrin binding site. It is
      hidden in the zymogen and expressed on A' and A*, indicating that the
      conformational change occurring with the cleavage of the activation peptide is
      sufficient to expose the fibrin binding site.

PMID- 1370211
TI  - Acute undifferentiated leukemia with CD7+ and CD13+ immunophenotype. Lack of
      molecular lineage commitment and association with poor prognostic features.
AB  - The authors studied six adult patients with acute leukemia with these unusual
      characteristics: unclassifiable morphology and undifferentiated cytochemistry by
      French-American-British (FAB) criteria; concurrent expression of CD13 (and CD33)
      myeloid and early T-cell CD7 immune markers; no evidence of T-cell lineage
      commitment as determined by T-cell receptor beta (beta), gamma (gamma), and delta
      (delta) chain gene rearrangement study and cytoplasmic CD3 epsilon expression;
      and no evidence of myeloid cell lineage commitment, as shown by absent myeloid
      specific c-fms proto-oncogene expression and negative myeloperoxidase
      ultrastructural staining (one case). Clinically, these diagnostic features
      matched with a poor prognosis, being associated with refractoriness to treatment,
      relapse and progression of disease, antecedent hematologic abnormality, and other
      malignancy. These cases may represent a distinct stem cell leukemia syndrome
      deserving immediate recognition and a nonconventional chemotherapeutic approach.

PMID- 1370212
TI  - Bone marrow hypoplasia and aplasia complicating interferon therapy for chronic
      myelogenous leukemia.
AB  - In four patients with Philadelphia chromosome-positive (Ph1) chronic myelogenous
      leukemia (CML), bone marrow hypoplasia (three patients) and aplasia (one patient)
      developed during or after therapy with either alpha-interferon (IFN) or gamma
      IFN. The predominant clinical characteristic of this complication was protracted
      pancytopenia, which required 2 to 5 months recovery time after treatment and did
      not resolve in one patient. Bone marrow cytogenetic analysis in two of the
      patients demonstrated 100% Ph1 metaphases despite the profound bone marrow
      suppression. Overall, this complication was uncommon, occurring in less than 2%
      of the patients with CML treated with various IFN. The possible underlying causes
      include previous therapy with alkylating agents, lack of "reservoir" or normal
      stem cells, or pronounced sensitivity of the malignant cell clone to the
      suppressive effect of IFN.

PMID- 1370213
TI  - Establishment of a human t(4;11) leukemia in severe combined immunodeficient mice
      and successful treatment using anti-CD19 (B43)-pokeweed antiviral protein
      immunotoxin.
AB  - Human acute leukemia, with a chromosomal translocation involving chromosomes 4
      and 11, t(4;11)(q21;q23), is the most common form of leukemia in infants and
      responds very poorly to conventional therapy. A human CD19+ mixed-lineage
      leukemia cell line with a t(4;11)(q21;q23) translocation, RS4;11, disseminated
      and proliferated in the hematopoietic tissues and other organs of mice with
      severe combined immunodeficiency in a manner similar to that observed in humans
      and killed 100% of the animals. The anti-CD19(B43)-pokeweed antiviral protein
      immunotoxin selectively inhibited clonogenic RS4;11 cells in vitro, markedly
      reduced the burden of disseminated leukemia of severe combined immunodeficient
      mice, and, most importantly, resulted in the long-term survival of treated
      animals. This severe combined immunodeficient mouse model should be useful for
      the design of more effective treatment strategies for refractory human leukemias.

PMID- 1370214
TI  - The NZB mouse as a model for chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western
      world and the only leukemia for which a possible genetic component has been
      described. Analysis of this genetic component has been hindered by the fact that
      disease onset normally occurs after age 50. We report here the aged NZB mouse as
      an animal model for CLL. NZB mice have a genetically regulated, age-dependent
      onset of clonal, aneuploid cells which are IgM+ and Ly1+ (CD5+ B-cells).
      Peripheral blood smears from old NZB mice show an increase in circulating
      lymphocytes and "smudged" or ruptured cells, often seen in human CLL. Electron
      microscopic examination of these cells shows them to be mature lymphocytes. Light
      microscopy of the spleen shows infiltration of small lymphocytes and is
      consistent with CLL pathology. These long-lived, CLL-like cells can be serially
      passaged into recipient animals. This continued passage occasionally results in
      the development of a large cell lymphoma detectable in the spleen, lymph nodes,
      and liver. The histology of this lymphoma is quite distinct from that of the CLL
      like cells, but the phenotype is that of an aneuploid CD5+, IgM+ cells. This
      apparently represents a continued transformation of the CLL-like clone similar to
      the development of Richter's syndrome in human CLL. Therefore, the NZB mouse can
      be a valuable tool for the determination of the genetic basis of CLL ontogeny and
      the conversion of CLL into Richter's syndrome.

PMID- 1370215
TI  - Ventricular arrhythmias in the absence of organic heart disease.

PMID- 1370216
TI  - Long- and short-term risk of sudden coronary death.
AB  - The long- and short-term relation of risk factors to sudden cardiac death (SCD)
      is examined in the Framingham heart study of 2,011 men and 2,534 women aged 35-70
      at the fourth biennial exam. Risk factor measurements over the first four
      biennial exams were averaged and analyzed as predictors of the long-term
      occurrence of SCD over the ensuing 28 years using Kaplan-Meier survival curves
      and the Cox proportional hazards method. The relation of risk factors to the
      short-term risk of SCD was examined by relating risk factors at each biennium to
      incidence over the ensuing 2 years, using pooled logistic regression analyses.
      Over the 28 years of follow-up, 171 men and 80 women experienced SCDs. Women had
      a lower incidence than men at all ages, and even after adjusting for known risk
      factors, their SCD rate was only 32% of that in men. In the short term, women
      have an SCD rate that is 23% of that in men. Most of the modifiable or
      constitutional risk factors, including glucose intolerance, systolic blood
      pressure, body mass index, and cigarette smoking have a greater long-term than
      short-term net effect. This is less apparent in women. Electrocardiographic
      abnormalities such as left ventricular hypertrophy, intraventricular block, and
      nonspecific repolarization abnormality were better short-term predictors. In men,
      preexisting coronary heart disease conferred a 3.3-fold (risk factor-adjusted)
      increased long-term risk of SCD and 5.3-fold increased short-term risk. In women,
      the long-term risk is 1.9 and short-term risk is 2.8.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1370217
TI  - Dextran administration avoids hemodynamic changes following paracentesis in
      cirrhotic patients. A safe and inexpensive option.
AB  - Paracentesis associated with albumin administration has been shown to be a safe
      and useful procedure in the treatment of patients with cirrhosis and ascites.
      Given the high cost of albumin, 20 patients with cirrhosis and ascites were
      treated in an open study, with daily paracentesis using dextran 70, an
      inexpensive volume expander, instead of albumin. In the first 10 patients,
      hemodynamic evaluation was performed in basal conditions, after each paracentesis
      (5 liter), and after dextran infusion. Twelve hours after each paracentesis
      without expansion, a significant drop in pulmonary capillary wedge pressure from
      9.5 +/- 1.0 to 7.1 +/- 1.7 (P less than 0.01) and a reduction in cardiac output
      from 6.6 +/- 1.0 to 5.0 +/- 1.9 (NS) were observed. Moreover, the hematocrit rose
      significantly from 36.8 +/- 5.6 to 39.2 +/- 4.8 (P less than 0.01). These
      parameters returned to baseline values after the administration of 84 +/- 14 ml
      of dextran 70 for each 1000 ml of ascites removed. The other 10 patients received
      dextran 70 simultaneously with the paracentesis without hemodynamic control. No
      significant changes in renal and hepatic functions were observed at the end of
      the study. The mean volume of ascites removed was 12.3 +/- 4.6 liter. Two
      patients developed hyponatremia that required no treatment. No patient developed
      renal failure. One patient died because of gastrointestinal bleeding.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1370218
TI  - A symptomatic female patient with Duchenne muscular dystrophy diagnosed by
      dystrophin-staining: a case report.
AB  - We report a case of symptomatic carrier of Duchenne muscular dystrophy (DMD) in a
      14-year-old girl with no prior family history of DMD. She presented with chest
      pain, enlarged calf muscles, an elevated serum creatine kinase (CK), and
      decreased left ventricular function. Histological examination of skeletal muscle
      revealed myopathic changes and immunostaining with anti-dystrophin antiserum
      demonstrated a mosaic pattern which are compatible with the observations in
      carriers of DMD. Southern blots using the dystrophin cDNA revealed no evidence of
      a deletion within the DMD gene in the patient or in her mother. We found this
      observation interesting for two reasons: 1. Cardiomyopathy is rare in female DMD
      patients. 2. Immunostaining of a muscle biopsy with anti-dystrophin serum proved
      to be valuable in the diagnosed for symptomatic carriers of the dystrophin gene
      mutation.

PMID- 1370219
TI  - Regeneration of the eighth cranial nerve in the bullfrog, Rana catesbeiana.
AB  - The present study was done in order to document the ability of the eighth cranial
      nerve of the bullfrog (Rana catesbeiana) to regenerate, the anatomic
      characteristics of the regenerated fibers, and the specificity of projections
      from individual endorgan branches of the nerve. The eighth cranial nerve was
      sharply transected between the ganglion cells and the brain stem in 40 healthy
      bullfrogs and allowed to regenerate. Anatomic studies were performed in these
      animals a minimum of 3 months postoperatively. Horseradish peroxidase was used to
      label the whole vestibular nerve or its individual endorgan branches. Labeled
      regenerated fibers could be identified crossing the site of the nerve section and
      projecting centrally to the vestibular nuclei in a pattern similar to that of
      normal frogs. Labeling of individual branches showed that regenerated fibers
      innervated the same specific areas found in normal frogs. Unlike normal animals,
      both thick and thin fibers projected to the medial nucleus.

PMID- 1370220
TI  - Does GAP-43 support axon growth by increasing the axonal transport velocity of
      calmodulin?
AB  - GAP-43 is a neuronal protein whose synthesis is elevated during developmental and
      regenerative axon growth. We propose that one consequence of this increased
      synthesis may be the delivery of calmodulin-like proteins to the distal portions
      of the growing axon at an increased velocity; this is because calmodulin, which
      is transported slowly in mature intact axons, can bind to GAP-43, which is
      transported rapidly. The release of calmodulin from GAP-43 would be regulated by
      phosphorylation by protein kinase C. Such a rapid carrier function could be
      important for allowing certain recently synthesized slowly transported proteins
      to reach the moving growth cone in time to support its function. This
      hypothetical carrier mechanism is consistent with the phosphorylation pattern,
      calmodulin binding, transport velocity, and growth-association of GAP-43, and
      suggests an explanation for the specific importance of newly synthesized GAP-43
      in supporting axon growth.

PMID- 1370221
TI  - Fetal cell grafts into resection and contusion/compression injuries of the rat
      and cat spinal cord.
AB  - This article reviews recent findings concerning the feasibility, basic
      neurobiology, and potential functional benefits of fetal CNS tissue grafts into
      acute and chronic lesions of the adult spinal cord. In the rat, neuro-anatomical
      observations suggest that transplants into resection cavities establish neuritic
      projections that could functionally reunite separated rostral and caudal segments
      of the host spinal cord. Furthermore, some complementary electrophysiological
      evidence has been obtained for synaptic connectivity between host and graft
      neurons. In these studies, extracellular single-unit activity was evoked in fetal
      spinal cord (FSC) transplants by stimulating host dorsal roots that had been
      juxtaposed to donor tissue at the time of transplantation. In other
      investigations, we examined whether grafts could also establish axonal
      projections to appropriate areas of gray matter in the chronically injured spinal
      cord. For this purpose, fetal serotoninergic (5-HT) neurons were injected caudal
      to complete spinal cord transections that had been made 1-3 months earlier.
      Immunocytochemistry revealed that these cells projected their axons into gray
      matter regions normally innervated by bulbospinal 5-HT neurons. To investigate
      transplantation in a more clinically relevant lesion model, a third group of
      experiments involved injection of dissociated cell suspensions into acute [less
      than 24 h postinjury (p.i.)]), subchronic (7-10 days p.i), and chronic (greater
      than or equal to one month, p.i.) contusion lesions. Such grafts routinely filled
      areas that otherwise would have been regions of cavitation extending rostral
      caudal distances of approximately 7 mm. FSC transplants in such injuries also
      appeared to influence some aspects of motoneuron excitability and hindlimb
      locomotion. More recent studies of the cat spinal cord have extended these
      findings in the rat by showing long-term survival (greater than 2 years) of fetal
      CNS allografts in recipients with either subtotal transection or compression
      lesions. Preliminary studies of connectivity have also shown host-graft
      projection patterns similar to those seen in the rat. Behavioral analyses are
      currently underway to examine the effects of fetal grafts in cats with chronic
      postcompression lesions. These observations in the rat and cat are discussed in
      the general context of basic biological and clinical issues relevant to the long
      term objective of promoting functional improvement in the damaged spinal cord.

PMID- 1370222
TI  - Receptor cell regeneration and connectivity in olfaction and taste.
AB  - The capacity of adult mammalian gustatory and olfactory receptor cells to
      regenerate and make synaptic reconnections provides examples that may be useful
      in initiating replacement of other kinds of sensory receptor cells. The sensory
      code for taste quality may not be degraded by taste receptor cell turnover
      because axons probably recouple to the appropriate type of new receptor cell by
      axon-receptor cell affinity. Experiments on the development and regeneration of
      taste receptor cells suggest that they regenerate and turn over by recapitulating
      the late but not the early steps in taste bud development. To evaluate the
      replacement of vertebrate olfactory receptors, we began by characterizing the
      spatial pattern of primary olfactory projections in rainbow trout. Contiguous
      clusters of HRP-labeled olfactory receptor neurons (ORN) make highly divergent
      projections to the olfactory bulb. Retrograde transport of fluorescent latex
      beads revealed that a given restricted site in the glomerular layer received
      axons from ORNs widely scattered in the epithelium. Hence, ORN axons do not form
      point-to-point or regional topographic maps. Rather, the olfactory epithelial
      sheet makes a plane-to-point or holographic-like projection, since any given
      point in the glomerular layer receives information from the entire olfactory
      epithelial plane. Receptor cells that reacted with the lectin pokeweed agglutinin
      were highly dispersed in the olfactory epithelium with axons widely scattered in
      the olfactory nerve. Yet, as a consequence of the extensive reaggregation of
      axons at the nerve-bulb interface, the lectin-positive axons fasciculated and
      converged into a subregion of the glomerular layer.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1370223
TI  - Functional properties of acetylcholine receptors coexpressed with the 43K protein
      in heterologous cell systems.
AB  - The nicotinic acetylcholine (ACh) receptor is an integral membrane protein which
      mediates synaptic transmission at the skeletal neuromuscular junction. A key
      event in the development of the neuromuscular junction is the formation of high
      density aggregates of ACh receptors in the postsynaptic membrane. Receptor
      clustering has been attributed, in part, to their association with a peripheral
      membrane protein of Mr 43,000 (43K protein). We have addressed whether the
      association of the 43K protein can alter the single channel properties of the ACh
      receptor, and thus influence neuromuscular transmission at developing synapses,
      by expressing ACh receptors with and without the 43K protein in heterologous
      expression systems. We found that coexpression of the 43K protein with the
      receptor did not significantly alter either its single channel conductance or its
      mean channel open time. This was true in oocytes and also in COS cells where it
      was possible to localize 43K-induced clusters by fluorescence microscopy and to
      record from those clustered receptors. These data are in agreement with previous
      single channel studies which have shown that the properties of diffusely
      distributed and clustered receptors in native muscle cells from both mice and
      Xenopus do not differ.

PMID- 1370224
TI  - Avian scale development. XVI. Epidermal commitment to terminal differentiation is
      prior to definitive scale ridge formation.
AB  - Germinative cells of the scutate scale epidermis from 15-day embryos are
      committed to appendage-specific, beta stratum formation in association with a
      foreign dermis. Commitment precedes the time (17 days of development) at which
      beta strata are actually present in their site-specific locations along the outer
      surface of each scutate scale. This observation suggested the possibility that
      commitment to beta stratum formation might be occurring as the outer epidermal
      surface of each scutate scale first becomes established between 12 and 13 days of
      development. It is at this time that the scale epidermis loses its ability to
      participate in feather morphogenesis and cell proliferation becomes restricted to
      a true stratum basale. To examined the ability of the presumptive scutate scale
      epidermis to generate beta strata in the absence of the inductive scutate scale
      dermis, scutate scale epidermis from 11-, 12-, and 13-day embryos was recombined
      with 15-day reticulate scale dermis and grown for 7 or 9 days. The dermis of
      reticulate scales does not induce beta stratum formation, but it does support
      differentiation of a beta stratum by the determined 15-day scutate scale
      epidermis. Using immunohistological and biochemical analyses of beta-keratins, we
      find that each of these presumptive scutate scale epidermises is competent to
      generate appendage-specific beta strata in the absence of the scutate scale
      dermis. This determination is occurring prior to scale ridge morphogenesis and
      differentiation of the epidermis into the distinct outer and inner epidermal
      surfaces of the scale ridge. The restricted distribution of beta strata to the
      apical domes of individual reticulate-like scales demonstrates that the
      germinative cells of the committed epidermises are responding to patterned cues.
      This study also suggests that all basal cells of the presumptive scutate scale
      epidermis are initially endowed with the ability to generate cells that form a
      beta stratum.

PMID- 1370225
TI  - Immunization against polyoma tumors with synthetic peptides derived from the
      sequences of middle- and large-T antigens.
AB  - We have used 9 synthetic peptides corresponding to sequences of polyoma virus
      small-T, middle-T and large-T antigens as immunogens in order to map antigenic
      epitopes that can induce polyoma-tumor-specific immunity in different mouse
      strains. We found that immunization of mice with synthetic peptides derived from
      amino acid (aa) sequences common to all 3 T-antigens (aa 1-19), or sequences
      common to only middle-T and small-T (aa 162-176), as well as synthetic peptides
      unique for middle-T (aa 269-282 and 371-381), or unique for large-T (aa 108-124,
      316-333 and 436-449) can induce immunity against polyoma tumors. The synthetic
      peptides can be divided into 3 types with regard to immunogenicity; (i) peptides
      that immunize in more than one mouse strain and may represent immunodominant
      sites, (ii) peptides that may be immunogenic in only one strain, and thus strain
      specific, and finally (iii) peptides that do not immunize in the strains tested
      so far.

PMID- 1370226
TI  - Haemopoietic cell kinetics in humans treated with rGM-CSF.
AB  - We have investigated the kinetics of myeloid cell proliferation in the marrow of
      patients with small-cell lung cancer and treated with 10 daily subcutaneous
      injections of granulocyte/macrophage colony-stimulating factor (GM-CSF). Bone
      marrow, obtained before and during treatment with the growth factor, was labelled
      in vitro with tritiated thymidine (3H-TdR). A 3rd bone-marrow sample was obtained
      1 hr following an intravenous injection of 3H-TdR. Subsequent daily blood samples
      were also collected, and 3H-TdR labelling was assessed on these and the marrow
      preparations by autoradiography. GM-CSF treatment increased the peripheral
      granulocytic cells nearly 5-fold, but this included significant eosinophilia, so
      that the neutrophilic granulocytes increased only 3.3-fold. These cells were
      released from the marrow over a normal time scale, but their peripheral half-life
      was about 6 times longer than normal and they were probably functionally
      defective. Furthermore, significant numbers of immature cells were released from
      the marrow. Neutrophil production stimulated by GM-CSF was thus overestimated by
      measurement of the apparent peripheral granulocytosis. Increased labelling
      indices and grain counts in the proliferating granulocytic cells of the marrow
      indicate shortened cell-cycle times, and the excess granulocyte production
      appears to be the result of extra amplification divisions in the proliferative
      compartments.

PMID- 1370227
TI  - Effects of interferons on the expression of the proto-oncogene HER-2 in human
      ovarian carcinoma cells.
AB  - The over-expression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian,
      endometrial and mammary carcinoma is an important indicator for poor prognosis.
      We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon
      gamma (IFN-gamma)-mediated reduction in HER-2 specific protein and RNA levels.
      The oncogene expression was lowered only in the ovarian carcinoma cell lines but
      not in 3 IFN-gamma-sensitive human breast cancer cell lines. We extended our
      observations also to IFN type I, alpha and omega. The expression of the oncogene
      was measured by both the p185HER-2 ELISA and in selected cases by a living cell
      radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the
      extracellular domain. Both IFN types reduced the expression of HER-2 in the
      ovarian carcinoma cell lines OVCAR-3, HTB-77, 2774 and SKOV-6, and in the SKUT-2
      endometrial carcinoma cells. In contrast, SKOV-8 human ovarian carcinoma cells
      were sensitive for both IFN types regarding proliferation, but only IFN-gamma
      reduced proto-oncogene expression. In the SKBR-3 human mammary carcinoma cells,
      neither IFN type had an effect on HER-2 expression. The antibodies 4D5, 7C2, 3E8,
      and 3H4 which bind to the extracellular domain of p185HER-2 protein specifically
      inhibited anchorage-independent growth of SKBR-3 and HTB-77 cells. Expression of
      the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its
      modulation might represent a mechanism by which IFNs inhibit cell proliferation.

PMID- 1370228
TI  - Localization of epidermal growth factor immunoreactivity in sheep skin during
      wool follicle development.
AB  - Interactions among the cells and matrices of the epidermis and mesenchyme of skin
      are essential for hair follicle initiation and development. The identification of
      receptors for epidermal growth factor (EGF) on epithelial components of the
      follicle during growth has suggested that the ligand participates in some of
      these events. We have used affinity-purified antibodies together with an alkaline
      phosphatase detection procedure to investigate the distribution of EGF in the
      skin of the sheep during wool follicle formation. Immunoreactivity was restricted
      to the periderm and intermediate layers of fetal epidermis at 55 d of gestation,
      when the first wave of wool follicles are initiated. This particular distribution
      persisted during subsequent development but never became associated with the
      basal cells of the epidermis. The activity was lost around 118 d, coinciding with
      sloughing of the periderm. No immunoreactivity was found in the plugs or the
      dermal condensations of the developing follicles. At approximately 105 d of
      gestation, however, reactions were detected in the outer root sheath as the
      follicles matured and in the differentiating cells of the sebaceous glands. A
      similar distribution pattern was also noted at 140 d, just prior to birth, and in
      adult animals, indicating that EGF was sequestered and perhaps synthesized within
      the follicle. The presence of immunoreactive material was also associated with
      the pilary canals and the skin surface, suggesting that this may have had its
      origin in the sebaceous glands. We examined this using a radioreceptor assay for
      EGF. Material washed from the skin surface and sebaceous gland extracts were
      found to displace 125I-EGF from rat liver membranes, in parallel with mouse EGF.

PMID- 1370229
TI  - A new cell type in normal human epidermis?

PMID- 1370230
TI  - Central rod domain insertion and carboxy-terminal fusion mutants of human
      cytokeratin K19 are incorporated into endogenous keratin filaments.
AB  - Keratins comprise a multigene family of structural proteins that form the 10-nm
      filaments present in epithelial cells. Keratin filament formation requires the
      presence of stoichiometric quantities of type I and type II keratin peptides.
      Each keratin peptide contains an N-terminal "head" segment, a C-terminal "tail"
      segment, and a highly conserved, alpha-helical central rod domain. To investigate
      the importance of these domains in situ, we have altered the DNA coding sequence
      of human cytokeratin K19 and transiently expressed the mutants in PtK2 cells that
      contain an endogenous keratin filament system. Interestingly, K19 mutants
      containing 4, 8, 12, and 24 amino acid insertions in the non-alpha-helical L1
      region of the central rod domain successfully integrate into the endogenous PtK2
      keratin filaments. Another K19 mutant, K19-bGAL, that encodes bacterial beta
      galactosidase (bGAL) fused in phase to the 3' end of the K19 central rod domain,
      also integrates into the endogenous PtK2 keratin filaments. Our results
      demonstrate 1) that the spacing between the highly conserved amino and carboxy
      terminal ends of the K19 central rod domain can be increased without
      significantly effecting K19's ability to interact with keratin filaments and 2)
      that addition of a highly soluble 66-kDa tail to K19 does not impede its
      interaction with the filament system.

PMID- 1370231
TI  - Culture of basal cell carcinoma.
AB  - Studies of basal cell carcinoma have been hindered by a lack of a suitable and
      reproducible tissue-culture model system. We have succeeded in growing this tumor
      in primary culture from eight different patients. We can separate and grow the
      tumor cells and the stromal cell component. We also culture normal keratinocytes
      and fibroblasts from the same patient for comparative studies. All the cell types
      have been subcultured four to five times and cryopreserved. The normal
      keratinocytes were indistinguishable from the tumor cells in ploidy, in rate of
      growth, and in the failure to express ICAM-1. Both cell types also fail to
      synthesize the matrix proteins: types I and IV collagens. Differences were noted
      in the expression of fibronectin and the bullous pemphigoid antigen, with the
      normal cells expressing the antigens although the tumor cells did not.
      Interferons exogenously added to the culture media preferentially killed the
      basal cell carcinoma cells, as compared to normal keratinocytes from the same
      patients. We believe that our culture system opens possibilities for biochemical
      and molecular studies of this disease, and for in vitro testing of antitumor
      agents for clinical therapy.

PMID- 1370232
TI  - Expression of the L-fucose moiety on infrainfundibular follicular keratinocytes
      of terminal follicles, its decreased expression on vellus and indeterminate
      follicles of androgenetic alopecia, and re-expression in drug-induced hair
      regrowth.
AB  - The distribution of various glycoprotein molecules on the surface of follicular
      keratinocytes was studied with a panel of lectins with specificity for various
      sugar moieties on biopsy specimens from both bald/balding scalp and normal
      occipital scalp, of 23 patients with androgenetic alopecia as well as on biopsies
      of normal forearm skin of four patients. The most significant differences between
      bald and normal scalp biopsy were noted with Ulex europaeus agglutinin I (UEA I).
      We noted an increased (91.8% +/- 3.1; mean +/- SE) expression of UEA I binding
      sites on the infra-infundibular follicular keratinocytes in anagen terminal scalp
      hairs, compared to 28.5% +/- 5.2 in the indeterminate (anagen) hairs of balding
      scalps, and 23.2% +/- 6.3 in the anagen follicles of vellus fore-arm hairs. By
      contrast, the telogen hairs demonstrated minimal UEA I staining: 4.0% +/- 0.8,
      mean +/- SE in telogen scalp hairs, 1.8% +/- 0.5 in telogen hairs of balding
      scalps (0% in completely bald scalps, in which all the hairs were in the telogen
      phase), and 1.9% +/- 0.2 in telogen forearm hairs. The percentage of UEA I
      staining correlated with the length of the infra-infundibular follicles in all
      cases studied. In three cases of hair regrowth after hair growth promotors, the
      UEA I staining increased to 80.6% +/- 6.1 in anagen hairs and correlated with
      increased length of infra-infundibular follicles. Our data indicate that there
      are 1) marked differences between anagen and telogen follicles in UEA I binding
      to infra-infundibular follicular keratinocytes; 2) the percentage of UEA I
      staining reflects the size (length) of the infra-infundibular hair follicle; and
      3) the anagen follicles of balding scalps (indeterminate hairs) show UEA I
      staining resembling that exhibited by anagen follicles of vellus hairs.

PMID- 1370233
TI  - VCAM-1-, ELAM-1-, and ICAM-1-independent adhesion of melanoma cells to cultured
      human dermal microvascular endothelial cells.
AB  - We have examined the mechanisms by which tumor cells bind to endothelial cells
      utilizing cultured melanoma cells and microvascular endothelial cells derived
      from human dermis (HDMEC). The ability of biologic response modifiers (BRM) to
      modulate the adhesion of melanoma cells to HDMEC was defined and those results
      were compared with results from human umbilical vein endothelial cells (HUVEC).
      SK-MEL-2, WM266-4, and Hs 294T melanoma cells all bound to HDMEC and HUVEC
      monolayers and adherence of melanoma cells was enhanced in a dose- and time
      dependent manner by the treatment of HDMEC with interleukin 1 (IL-1) alpha or
      tumor necrosis factor (TNF) alpha. Similar increases in binding to HDMEC or HUVEC
      were induced after BRM stimulation, although baseline melanoma cell binding to
      HUVEC tended to be slightly higher than to HDMEC. In contrast, whereas phorbol 12
      myristate 13-acetate (PMA) augmented melanoma cell adherence to HDMEC, PMA failed
      to increase adherence to HUVEC. The alterations in melanoma cell binding were
      induced only after pretreatment of endothelial and not melanoma cells with PMA.
      Studies of the expression of cell adhesion molecules (CAM) on HDMEC and HUVEC
      using enzyme-linked immunosorbent assay showed that vascular cell adhesion
      molecule 1 (VCAM-1) is not induced by PMA on HDMEC and intercellular adhesion
      molecule 1 (ICAM-1) is downregulated on HDMEC by PMA treatment. Endothelial
      leukocyte adhesion molecule 1 (ELAM-1) is induced by PMA, IL-1 alpha, or
      TNFalpha, but its expression does not correlate with increased melanoma cell
      binding MoAb recognizing VCAM-1-inhibited TNFalpha-induced increases in melanoma
      cell binding to HUVEC. However, anti-VCAM-1 antibody failed to clock melanoma
      cell binding to PMA or IL-1 alpha-stimulated HDMEC and only partially inhibited
      melanoma cell binding to TNF alpha-stimulated HDMEC. This study demonstrates that
      PMA and IL-1 alpha-induced increases in melanoma cell adherence to HDMEC are not
      mediated via known CAM, including ICAM-1, VCAM-1, or ELAM-1, and may be affected
      through microvessel-specific novel proteins not previously described on
      endothelial cells.

PMID- 1370234
TI  - Comparison of the University of Wisconsin preservation solution and other
      crystalloid perfusates in a 30-hour rabbit lung preservation model.
AB  - The University of Wisconsin solution, which contains a high potassium
      concentration (120 mmol/L), was evaluated for rabbit lung preservation by
      comparing it with a modified University of Wisconsin solution with low potassium
      (4 mmol/L), a low-potassium dextran solution (4 mmol/L), and simple surface
      cooling. In the first three groups rabbit lungs were flushed in situ with the
      solution (n = 5 in each group); then the lung-heart block was harvested and
      stored at 10 degrees C for 30 hours. In the surface cooling group the lungs were
      harvested without flushing and then simply immersed in saline and stored. For
      assessment, the stored lung was ventilated with room air and perfused with fresh
      venous blood at a rate of 40 ml/min for 10 minutes. Assessment of lung function
      included gas analysis of effluent blood, mean pulmonary artery perfusion
      pressure, and peak airway pressure. Among these parameters, oxygen tension was
      most sensitive. Oxygen tension at 10 minutes' perfusion in the modified
      University of Wisconsin (95 +/- 6 mm Hg) and low-potassium dextran (99 +/- 4 mm
      Hg) groups was significantly higher than that in the surface cooling (61 +/- 7 mm
      Hg) and University of Wisconsin (51 +/- 7 mm Hg) groups. There was no difference
      between the modified University of Wisconsin and low-potassium dextran groups or
      between the surface cooling and University of Wisconsin groups. We conclude that
      the low-potassium University of Wisconsin solution is superior to the high
      potassium University of Wisconsin solution and that the lactobionate and
      raffinose included in the University of Wisconsin solution as impermeants do not
      improve lung preservation in this model.

PMID- 1370235
TI  - BEAM regimen and G-CSF in HTLV-I-associated T-cell lymphoma.

PMID- 1370237
TI  - Membrane dihydrolipoamide acetyltransferase (E2) on human biliary epithelial
      cells in primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is associated with serum antibodies that react
      with the dihydrolipoamide acetyltransferase component (E2) of the mitochondrial
      pyruvate dehydrogenase complex. We have sought the presence of E2 on the surface
      of human intrahepatic biliary epithelial cells (BEC). Cultured BECs from PBC but
      not normal liver were found to have E2 on the membrane after three days' culture.
      Isolated, viable cells examined by laser-scanning confocal microscopy revealed
      the pattern of E2 staining on the membrane to be similar to that seen with the
      membrane glycoprotein marker, HEA-125. By contrast, BECs from normal liver showed
      membrane staining only with HEA-125. When BECs were fixed before incubation with
      antibody to E2, cytoplasmic staining was observed. Our results suggest that E2 is
      present on the surface of biliary epithelial cells in PBC, and support the idea
      of a pathogenetic association between antimitochondrial antibodies and bileduct
      damage.

PMID- 1370236
TI  - Cutaneous responses to vasoactive intestinal polypeptide in chronic idiopathic
      urticaria.
AB  - Cutaneous wheal and flare responses to increasing concentrations of calcitonin
      gene-related peptide, substance P, neurokinin A, vasoactive intestinal
      polypeptide (VIP), compound 48/80, and phosphate-buffered saline were measured in
      10 patients with chronic idiopathic urticaria and 10 healthy controls. A
      significant increase in VIP-induced wheal, but not flare or cutaneous blood flow,
      was seen in urticarial patients compared with controls (p less than 0.001). No
      significant differences in responses to other tested compounds were found between
      these groups. These data point to an increased sensitivity of microvasculature to
      VIP in patients with chronic idiopathic urticaria.

PMID- 1370238
TI  - Cytosolic activation of 2-aminoanthracene: implications in its use as diagnostic
      mutagen in the Ames test.
AB  - The metabolic activation of 2-aminoanthracene to mutagens in the Ames test was
      investigated using hepatic S9, microsomal and cytosolic fractions from control
      and Aroclor 1254-treated rats as activation systems. Microsomal and S9
      preparations from control animals could activate 2-aminoanthracene, but the
      efficiency of activation was suppressed by pretreatment of animals with Aroclor
      1254. Cytosolic fractions from Aroclor 1254-treated rats could readily activate
      the promutagen more readily than microsomes. The cytosolic activation of 2
      aminoanthracene required NADPH and could not be accounted for by possible
      microsomal contamination. The molybdenum oxygenases appear not to contribute to
      the cytosolic activation of this promutagen. It is concluded that (a) the
      microsomal activation of 2-aminoanthracene is catalysed more effectively by
      enzyme systems other than the P450 I family and (b) an enzyme system capable of
      activating this carcinogen in vitro is present in the hepatic cytosol. The
      implications of these findings in the use of 2-aminoanthracene as a positive
      control in the Ames test are discussed.

PMID- 1370239
TI  - Induction of the cytoplasmic 'petite' mutation by chemical and physical agents in
      Saccharomyces cerevisiae.
AB  - A range of physical and chemical agents induce the mitochondrial 'petite'
      mutation in the yeast Saccharomyces cerevisiae. DNA intercalating agents as well
      as chemicals which can interfere with DNA synthesis induce this mutation, but
      only in growing cells. Many chemical or physical agents that produce a DNA lesion
      which is not simply reversed can induce various levels of the petite mutation,
      and may be more effective in non-growing cells. A limited number of chemicals act
      like ethidium bromide, inducing a high frequency of petites which is partially
      reversible with increasing concentration or time. The ability of a specific
      compound to be transported into mitochondria or its affinity for AT base pairs in
      DNA may determine whether it acts primarily as a nuclear or mitochondrial
      mutagen. In mammalian cells, some neoplastic changes occur at the mitochondrial
      level. Analogies between yeast and mammalian mitochondria suggest that agents
      which increase petite mutagenesis in yeast may have some carcinogenic potential.
      Although some types of petite inducer may have potential as antitumour drugs,
      those which are very effective antimitochondrial agents appear to be too toxic
      for therapeutic use. A process comparable to early stages in petite mutagensis
      occurs in human degenerative diseases and it seems possible that a consequence of
      exposure to petite mutagens could be an increase in the rate of degenerative
      diseases or of the aging process.

PMID- 1370240
TI  - Stable expression of monkey cytochrome P-450IA1 cDNA in Chinese hamster CHL cells
      and its application for detection of mutagenicity of aflatoxin B1.
AB  - A monkey cytochrome P-450IA1 cDNA (MKah1) was transfected into Chinese hamster
      CHL cells using a vector containing the SR alpha promoter, and sublines stably
      expressing P-450IA1 were established. The cells showed 25-fold higher sensitivity
      to the cytotoxic effect of aflatoxin B1 than the parental CHL cells. This
      hypersensitivity was almost completely suppressed by alpha-naphthoflavone, which
      is a known specific inhibitor of P-450IA. The cells expressing P-450IA1, but not
      CHL cells, showed a positive response to aflatoxin B1 in an assay for
      mutagenicity at the HGPRT locus.

PMID- 1370242
TI  - A quantitative assessment of the cytotoxicity associated with chromosomal
      aberration detection in Chinese hamster ovary cells.
AB  - Regulatory guidelines suggest testing chemicals up to cytotoxic doses in
      chromosomal-aberration assays. To investigate the utility and limitations of
      various cytotoxicity indicators we used Chinese hamster ovary (CHO) cells to test
      8 chemicals with differing ratios of cytotoxicity to clastogenicity. We measured
      immediate or delayed cell killing and growth inhibition (ATP levels, cell counts,
      colony-forming efficiency, CFE) and cell-cycle perturbations (mitotic index, MI;
      average generation time, AGT). Aberrations (abs) were scored 10 and 24 h from the
      beginning of the 3-h treatment. All 8 compounds induced abs at concentrations
      that reduced cell growth at 24 h by 50% or less. Concentrations of each chemical
      which induced at least 15% cells with abs, gave little loss of CFE (0-20%) for
      mitomycin C, adriamycin, cadmium sulfate and 2,6-diaminotoluene in contrast to
      the marked loss of CFE (70-80%) for eugenol (EUG), 2-aminobiphenyl and 8
      hydroxyquinoline (8-HQ). 2,4-Diaminotoluene (2,4-DAT) was intermediate. Higher
      aberration yields were found at 24 h than at 10 h, even when minimal cell-cycle
      delay was detected by AGT estimates from BrdUrd-labeled cells. Cells with
      multiple abs were seen at 24 but not at 10 h, and often confirmed clastogenicity
      when there was only a weak increase in the percentage of cells with aberrations.
      Total ATP per culture did not always correlate with cell number, especially at
      later times after treatment. This is likely due to metabolic perturbations or
      altered cell biomass that are known to affect cell ATP content. MI suppression
      often did not correlate with AGT, e.g., only small increases in AGT were seen for
      8-HQ, 2,4-DAT and EUG despite severe mitotic suppression at 10 h. By 24 h the MI
      for all chemicals had recovered, sometimes exceeding control levels. Marked
      mitotic accumulation was seen at 10 h for 2,4-DAT, indicating cell synchrony.
      Thus, the MI has limited value for dose selection. In conclusion, even weakly
      active chemicals were detected at a single time without exceeding a 50% growth
      reduction at 24 h.

PMID- 1370241
TI  - Effect of sampling time on chromosome aberration yield for 7 chemicals in Chinese
      hamster ovary cells.
AB  - Choice of harvest time is one of the most important variables in the assessment
      of whether a compound is clastogenic and in establishing a dose relation. We
      examined the effects of sampling time on aberration yield for 7 diverse chemicals
      in CHO-WBL cells by harvesting at intervals from 9 to 30 h after treatment for 3
      h with or without S9 metabolic activation. We observed both the percentage of
      aberrant cells and the total number of aberrations. Our data suggest that for
      most compounds a single harvest time approximately 17-21 h after the beginning of
      a 3-h treatment is optimal for aberration detection in CHO cells. Maximal
      aberration yields were observed for 2,4-diaminotoluene, 2,6-diaminotoluene and
      cytosine beta-D-arabinofuranoside from 17 to 21 h, eugenol from 15 to 21 h,
      cadmium sulfate from 15 to 24 h and 2-aminobiphenyl, from 17 to 24 h. For
      adriamycin at 1 microM, the % aberrant cells remained elevated throughout the
      period from 9 to 29 h, while small increases at 0.1 microM ADR were found only at
      13 and at 25 h. For most chemicals the maximal aberration yield occurred at a
      different time for each concentration tested. However, the use of 3 or more
      closely spaced concentrations, carefully selected to yield up to 50% toxicity,
      allowed detection of a positive response at a single harvest time for all 7
      chemicals.

PMID- 1370243
TI  - Structural requirements for the induction of the SOS repair in bacteria by
      nitrated polycyclic aromatic hydrocarbons and related chemicals.
AB  - The CASE (computer-automated structure evaluation) methodology was used to
      investigate the structural basis of the SOS-inducing activity of 56 nitrated
      polycyclic aromatic hydrocarbons (nitroarenes, nPAH) and the unsubstituted parent
      PAH molecules. Based upon the presence and/or absence of structural features,
      CASE identified 5 activating (biophores) and 4 inactivating (biophobes) fragments
      responsible for the SOS-inducing activity. Based upon these fragments, CASE
      correctly calculated the genotoxicity of 94.6% of the molecules in the training
      set (sensitivity = 0.85, specificity = 1.0). Disregarding the questionable
      experimental results of the unexpected very weak direct-acting activity of the
      unsubstituted benzo[a]pyrene, dibenzo[a,h]anthracene and 7,12
      dimethylbenz[a]anthracene, the concordance of the prediction was 100%, i.e.,
      sensitivity = 1.0, specificity = 1.0. Additionally, the quantitative analysis of
      the SOS-inducing potency showed a good correlation between the experimental and
      predicted results. The present analyses indicate an identity in the structural
      determinants responsible for SOS induction in E. coli PQ37 (SOS chromotest) and
      mutagenicity in Salmonella typhimurium.

PMID- 1370244
TI  - Oxygen species and the genotoxicity of quercetin.
AB  - Quercetin has been extensively studied in various short-term assays for
      genotoxicity. The patterns of genotoxicity of quercetin for different genetic
      endpoints are subject to a variety of factors (pH, antioxidants, metabolism)
      whose precise role in each test remains unclear. In the present study we report
      on the possible effect of oxygen-derived species on the activity of quercetin in
      the Ames assay and in the SOS chromotest. Our results seem to suggest that
      superoxide dismutase (SOD) does not account for the levels of mutagenicity
      detected in the presence of S9 or S100. The latter may, however, contain other
      factors of antioxidant defense which may prevent the oxidative degradation of
      quercetin. Since this degradation occurs at pH values above neutrality and the
      SOS-inducing activity is higher at pH 6.0, it is concluded that the response of
      quercetin in the SOS chromotest is due to quercetin itself at acidic pH. The SOS
      inducing activity at pH 7.4 is enhanced by SOD, but it cannot be unambiguously
      concluded that this effect in the SOS chromotest might only be due to protection
      against the oxidative degradation of quercetin.

PMID- 1370245
TI  - Involvement of RecB-mediated (but not RecF-mediated) repair of DNA double-strand
      breaks in the gamma-radiation production of long deletions in Escherichia coli.
AB  - Experiments were designed to determine the association between the repair of
      gamma-radiation-induced DNA double-strand breaks (DSB) and the induction of 700
      1000 bp long deletions (Lac(-)----Lac+), base substitutions (leuB19----Leu+), and
      frameshifts (trpE9777----Trp+) in Escherichia coli K-12. Over the range of 2.5-20
      krad, deletions were induced with linear kinetics, as has been shown for the
      induction of DSB, while the induction kinetics of base substitutions and
      frameshifts were curvilinear. Like the repair of DSB, deletion induction showed
      an absolute requirement for an intact recB gene as well as a dependency on the
      type of preirradiation growth medium; these requirements were not seen for base
      substitutions or frameshifts. In addition, about 80% of the spontaneous deletions
      were absent in the recB21 strain. A recC1001 mutation, which confers a 'hyper
      Rec' phenotype, increased the rate of gamma-radiation-induced deletions as well
      as the low-dose production of base substitutions and frameshifts. A recF143
      mutation increased the yield of gamma-radiation-induced deletions without
      increasing base substitutions or frameshifts. A mutS mutation markedly enhanced
      the gamma-radiation induction of frameshifts, and had a slight effect on base
      substitutions, but did not affect the induction of deletions. Resistance to gamma
      irradiation and the capacity to repair DSB (albeit at about half the normal rate)
      were restored to the radiosensitive recB21 strain by the addition of the sbcB21
      and sbcC201 mutations. However, the radioresistant recB sbcBC strain, which is
      recombination proficient via the RecF pathway, was still grossly deficient in the
      ability to produce deletions. A model for deletion induction as a by-product of
      the recB-dependent (Chi-dependent) repair of gamma-radiation-induced DSB is
      discussed, as is the inability to detect deletions in cells that use only the
      recF-dependent (Chi-independent) mechanism to repair DSB.

PMID- 1370246
TI  - Chromosome rearrangements associated with CAD gene amplification. Experiments
      with cell hybrids.
AB  - Resistance to phosphonacetyl-L-aspartate (PALA) is caused by CAD gene
      amplification. The marker chromosome of a PALA-resistant cell line containing a
      homogeneously staining region with amplified CAD gene was introduced into PALA
      sensitive Chinese hamster cells by microcell-mediated chromosome transfer. Two
      monochromosomal hybrids containing the marker chromosome in addition to the
      normal chromosome complement of sensitive cells and 1 tetraploid hybrid
      containing the complete genomes of donor (resistant) and recipient (sensitive)
      cells were studied in detail. It was shown that (i) the presence of the marker
      chromosome was both a necessary and a sufficient condition for the expression of
      the PALA-resistant phenotype; (ii) the marker chromosome underwent rearrangements
      in the monochromosomal hybrids, with preferential loss of non-amplified
      chromosomal regions, while it was not rearranged in the tetraploid hybrid; (iii)
      unlike the original PALA-resistant cells obtained after long-term selection in
      the presence of PALA, the PALA-resistant hybrids did not show chromosomal
      aberrations of other than the marker chromosome. This result indicates that
      chromosomal aberrations may be due to the selective procedure and is not an
      inherent property of cells containing amplified genes.

PMID- 1370247
TI  - Allergic rhinitis. Measures to control the misery.
AB  - Chronic fatigue, recurrent otitis and sinusitis, and poor performance at school
      or at work are among the many physical and psychosocial consequences of allergic
      rhinitis. Antihistamines, decongestants, and nasal sprays may be used to treat
      many patients, but immunotherapy may be necessary or more practical in others. In
      all cases, control of the patient's home environment, particularly the bedroom,
      is essential.

PMID- 1370248
TI  - Value of balloon dilation in treatment of youthful patients with prostatism.
AB  - Forty-three youthful patients with uncomplicated prostatism were prospectively
      evaluated to test the safety and efficacy of transurethral balloon dilation
      (TUDP). Treatment consisted of cystoscopic placement of an intraprostatic balloon
      inflated to 25 mm diameter at 3 atm pressure for ten minutes. At longest follow
      up (9.8 months, average; 3-24 months, range), 88 percent of patients were
      satisfied with overall treatment results. The average improvements in voiding
      symptom score and peak uroflow were 77 percent and 73 percent, respectively. Mean
      improvements over pretreatment levels were statistically significant at one month
      (p less than 0.01) and remained so for the entire follow-up period. No
      incontinence, impotency, retrograde ejaculation, sepsis, or serious bleeding
      developed. An intraprostatic fissure, which spared the bladder neck, was a
      uniform finding and the most likely mechanism of lasting action of TUDP. In the
      relief of uncomplicated prostatism in youthful patients, TUDP compares favorably
      with other treatment alternatives.

PMID- 1370249
TI  - A new brain glucosensor and its physiological significance.
AB  - The concentration of fibroblast growth factor (FGF), which is found in
      cerebrospinal fluid (CSF), markedly increases after the start of feeding. Food
      intake was dose-dependently suppressed by picomole doses of FGF and facilitated
      by anti-FGF antibody. This suppression was caused by activation of protein kinase
      C in glucose-sensitive neurons in the lateral hypothalamus. In situ hybridization
      by use of cDNA showed that acidic (a)FGF was produced in ependymal cells. The
      ependymal cells released aFGF by responding to glucose increase in CSF after
      feeding. Released aFGF diffused into the brain parenchyma and was taken by
      neurons. Passive avoidance was significantly more reliable after aFGF infusion
      into CSF. Clamping cerebral arteries in the gerbil induced ischemia, which
      damaged neurons in the CA1 layer of the hippocampus. Pretreatment with aFGF
      prevented this damage. Thus, aFGF is not only the most potent substance yet found
      for the suppression of feeding, but it is also extremely effective as a
      neurotrophic and memory facilitating substance.

PMID- 1370250
TI  - Insulin signal transduction: the role of protein phosphorylation.
AB  - Recent evidence suggests that the mechanism of insulin action depends in part on
      protein phosphorylation on tyrosine residues. A cascade of
      phosphorylation/dephosphorylation reactions is proposed to modulate multiple
      enzymes involved in metabolism, protein synthesis, and cell growth. Direct
      evidence is presented for the phosphorylation of myelin basic protein and
      microtubule-associated protein 2 on tyrosine residues by the insulin receptor.

PMID- 1370251
TI  - Antithyroid drug-induced agranulocytosis: is routine white blood cell count
      effective for the detection?

PMID- 1370252
TI  - A new generation of animal cell expression vectors based on the Semliki Forest
      virus replicon.
AB  - We have developed a novel DNA expression system, based on the Semliki Forest
      virus (SFV) replicon, which combines a wide choice of animal cell hosts, high
      efficiency and ease of use. DNA of interest is cloned into SFV plasmid vectors
      that serve as templates for in vitro synthesis of recombinant RNA. The RNA is
      transfected with virtually 100% efficiency into animal tissue culture cells by
      means of electroporation. Within the cell, the recombinant RNA drives its own
      replication and capping and leads to massive production of the heterologous
      protein while competing out the host protein synthesis. The expression system
      also includes an in vivo packaging procedure whereby recombinant RNA is packaged
      into infectious virus particles using cotransfection with packaging-deficient
      helper RNA molecules. The resulting high titer recombinant virus stock can be
      used to infect a wide range of animal cells with subsequent high expression of
      the heterologous gene product, but without expression of any structural proteins
      of the helper. The infected cells produce protein for up to 75 hours post
      infection after which the heterologous product can constitute as much as 25% of
      the total cell protein. The general utility of the system is demonstrated through
      the expression of human transferrin receptor, mouse dihydrofolate reductase,
      chick lysozyme and Escherichia coli beta-galactosidase.

PMID- 1370255
TI  - Analysis of the expression of CD5 by human B cells and correlation with
      functional activity.
AB  - B cells expressing the CD5 marker in the mouse have been suggested to be a
      separate lineage and a major source of autoantibody production. In man, this
      relationship is less clear. Studies were therefore undertaken to determine
      whether human CD5+ B cells represent a distinct lineage of cells that differ in
      patterns of antibody production from CD5- B cells. In normal B cell populations,
      CD5 was expressed by a mean of 24.0 +/- 2.8% (n = 10) of CD20+ B cells. Of note,
      an increased frequency of CD5+ B cells was not found in patients with systemic
      lupus erythematosus (mean of 17.9 +/- 2.8%, n = 16). Analyzing CD5+ B cells for
      cell membrane Ig isotype expression demonstrated similar frequencies of IgG and
      IgA expressing cells as were found on the CD5- B cell population, although the
      frequency of IgM+ cells was slightly increased. Incubation of CD20+ B cells with
      phorbol myristate acetate (PMA) for 72 hr increased the frequency of CD5
      expressing B cells by more than threefold. CD5 expression was also increased by
      coculture with anti-CD3-activated T cells and most markedly by simultaneous
      stimulation with both PMA- and anti-CD3-activated T cells (greater than 50%
      positive). Analysis of CD5- B cells clearly indicated that stimulation with PMA
      or anti-CD3-activated T cells induced the majority to become CD5+ transiently.
      Functional analysis of Ig production by CD5+ and CD5- B cells stimulated with
      anti-CD3-activated T cells indicated that both populations in normals produced
      IgM and a variety of autoantibodies in comparable amounts, whereas the CD5- B
      cells produced greater quantities of IgG. B cells were activated with anti-CD3
      stimulated T cells followed by separation into CD5+ and CD5- populations. The
      largest amount of Ig was produced by CD5- B cells that were induced to express
      CD5, although all populations produced some Ig. These data suggest that CD5
      behaves as an activation marker on human B cells rather than as a marker for a
      distinct lineage of cells. Moreover, CD5 expression does not appear to identify a
      population of resting B cells with a greater capacity to produce antibodies to
      DNA or other autoantibodies.

PMID- 1370254
TI  - Regulation of myelin basic protein-specific helper T cells in multiple sclerosis:
      generation of suppressor T cell lines.
AB  - Suppressor T cell (Ts) lines specific for myelin basic protein (MBP)-reactive
      helper T cell (Th) clones were generated from two patients with multiple
      sclerosis (MS) following a primary culture of peripheral blood mononuclear cells
      (PBMC) with MBP and cyclosporine A (CsA). These suppressor T cell lines were
      maintained in culture by alternate stimulation with MBP and antigen-presenting
      cells (APC). The Ts lines expressed preferentially the CD4 phenotype (5/6 Ts
      lines tested) and exhibited potent antigen-specific suppressor activity on the
      proliferation of MBP-specific Th clones and not on the T cell lines with other
      antigen specificity. For some Ts lines, a Ts-to-Th ratio of 1 was sufficient to
      inhibit the proliferation of MBP-specific T cells by 90%. The suppressor T cells
      obtained were weakly responsive to MBP and required the presence of the
      autologous PBMC for proliferation. Furthermore, proliferation of these suppressor
      T cell lines was restricted by HLA-DR molecules (for CD4+ Ts lines) and HLA class
      I (for a CD8+ Ts line). The suppressor T cell lines generated and the techniques
      described in this study may be helpful in our understanding of the events
      involved in the immune regulation in MS and other autoimmune diseases.

PMID- 1370253
TI  - Stimulator cell-dependent requirement for CD2- and LFA-1-mediated adhesions in T
      lymphocyte activation by superantigenic toxins.
AB  - The staphylococcal enterotoxins and related microbial T cell mitogens stimulate T
      cells by cross-linking variable parts of the T cell receptor (TCR) with MHC class
      II molecules on accessory or target cells. We have used cloned human T cells and
      defined tumor cells as accessory cells (AC) to study the requirements for T cell
      activation by these toxins. On AC expressing high levels of CD54 (intercellular
      adhesion molecule-1, ICAM-1) and CD58 (lymphocyte function-associated antigen-3,
      LFA-3), mAb to CD2 were relatively ineffective in inhibiting the response to the
      toxins and antibodies to the lymphocyte function-associated antigen-1 (LFA-1) did
      not inhibit at all. If added together, however, these mAb inhibited the response
      completely. Similar results were obtained using antibodies to the target
      structures of CD2 and LFA-1. In contrast, on cells expressing low levels of LFA
      3, mAb to LFA-1 but not to CD2 were strongly inhibitory. The same pattern of
      inhibition was found when these same cells were used as presenters of specific
      antigen to the T cells. These data show that adhesions via CD2 or LFA-1 are
      alternatively required for the stimulation of the T cells by superantigenic
      toxins and demonstrate another similarity between T cell stimulation by
      superantigens and by specific antigen recognition.

PMID- 1370256
TI  - B cell presentation of a tolerogenic signal to Th clones.
AB  - Lightly irradiated (950 R) splenic B cells were inefficient, in comparison to
      unseparated spleen cells, in stimulating antigen-specific proliferation of Th1
      clones specific for human gamma globulin (HGG). This inefficiency was due to
      antigen-specific inactivation: Th1 clones preincubated with HGG and lightly
      irradiated B cells or mitomycin C-treated B cells were unable to proliferate to
      HGG in secondary cultures. In contrast to Th1 clones, Th2 clones proliferated
      well in response to B cell APC, and showed no decrease in their subsequent
      antigen-induced proliferative capacity after exposure to lightly irradiated B
      cells and HGG. However, preincubation of Th2 with lightly irradiated B cells and
      HGG did inactivate the capacity of Th2 to provide help for antibody production in
      secondary cultures. These results suggest that under certain conditions B cells
      may present antigen to Th1 and Th2 cells in a tolerogenic rather than an
      immunogenic manner.

PMID- 1370257
TI  - A dual anti-tumor effect of a combination of interferon-alpha or interleukin-2
      and 5-fluorouracil on natural killer (NK) cell-mediated cytotoxicity.
AB  - Previous in vitro and in vivo studies have shown a synergism between interferon
      (IFN) and 5-fluorouracil (5-FU) against different tumor cell lines. In the
      present study we report that the combination of IFN-alpha and 5-FU has a
      significant effect not only on the inhibition of tumor cell growth but also on
      the regulation of natural killer cell-mediated cytotoxicity (NK-CMC). The
      addition of 5-FU to effector cell population neither affects NK cell activity nor
      activation of NK cells by IFN or by interleukin (IL)-2. However, pretreatment of
      target cells with 5-FU increased their susceptibility to NK activity and
      abolished the protective effect induced by IFN against NK-CMC. This dual effect
      of IFN-alpha and 5-FU was found to be applicable to target cells of different
      origins including a cervical carcinoma cell line (ME-180), a hairy cell leukemia
      like cell line (Eskol), a CML cell line (K-562) and a primary culture of AIDS
      related Kaposi's sarcoma cells. Similar results were found with IL-2 treatment of
      Eskol cells but not other cells. Combination of IL-2 with 5-FU resulted in
      enhancement of the sensitivity of the cells to NK activity and abolished the
      protection against NK-CMC. Based on these results we propose that the combination
      of IFN-alpha and 5-FU not only has a direct growth inhibitory effect on tumor
      cells but also has a regulatory role on the immunological arm of the NK-CMC.
      Moreover, since the combination gave the same pattern of response in different
      tumor cells, both NK-sensitive and NK-resistant, this combination treatment may
      be a candidate for clinical trials in various types of tumors.

PMID- 1370258
TI  - A common epitope is recognized by monoclonal antibodies prepared against purified
      human neutrophil Fc gamma RIII (CD16).
AB  - Fc gamma RIII is one of two Fc gamma R constitutively expressed by human
      neutrophils. We have prepared a panel of anti-Fc gamma RIII mAb following
      immunization of mice with Fc gamma RIII purified from human neutrophils. Ten mAb
      which reacted with neutrophils, NK cells, and monocyte-derived macrophages were
      produced. Immunohistochemical staining demonstrated that these mAb also
      identified macrophages in the red pulp of spleen. Competitive cross-inhibition
      binding assays demonstrated that nine of the ten mAb reacted with a common
      epitope that is spatially associated with the ligand binding site. These nine mAb
      blocked the binding of immune complexes to neutrophils by 65 to 90%. In addition,
      two other anti-CD16 mAb, which also blocked immune complex binding to
      neutrophils, inhibited the binding of each of these nine mAb to neutrophils. One
      of the mAb produced here, 214.1, failed to block immune complex binding. In
      addition to immunoprecipitating the native Fc gamma RIII glycoprotein, mAb 214.1
      was capable of immunoprecipitating a 28-kDa polypeptide following deglycosylation
      of Fc gamma RIII isolated from neutrophils. The results of cross-competition
      experiments suggest that mAb 214.1 may recognize the epitope identified by mAb
      BW209/2. Thus mAb 214.1 identifies a polypeptide epitope distinct from the ligand
      binding site of Fc gamma RIII on neutrophils.

PMID- 1370259
TI  - In vivo depletion of CD4 T cells increases B cell sensitivity to polyclonal
      activation: the role of interferon-gamma.
AB  - Chronic in vivo depletion of CD4+ T cells results in a marked increase in serum
      IgM levels. When normal mice were acutely depleted of CD4+ T cells,
      unfractionated spleen cell cultures showed an increased sensitivity to
      lipopolysaccharide (LPS)-induced IgM secretion. Sensitivity to LPS-induced
      proliferation was similar in both control cultures and cultures from CD4-depleted
      donors. When exogenous recombinant murine interferon-gamma (IFN-gamma) was added
      to spleen cell cultures from CD4-depleted donors, the sensitivity to LPS-induced
      IgM secretion was restored to the level seen in spleen cell cultures from control
      animals. IFN-gamma did not influence the proliferative response of purified B
      cells to LPS but was capable of profoundly inhibiting the LPS-induced
      differentiation of purified B cells. Thus the effect of IFN-gamma was anti
      differentiative and was exerted directly on the B cell. Finally, the LPS-induced
      differentiation of normal spleen cells was enhanced in the presence of mAb
      directed against IFN-gamma. These findings illustrate that IFN-gamma plays a key
      role in regulating the B cell compartment response to LPS-induced
      differentiation. The hyper-IgM syndrome seen in association with CD4 T cell
      depletion may be due to a loss of in vivo production of IFN-gamma.

PMID- 1370260
TI  - Expression of CD45 isoforms by Epstein-Barr virus-transformed human B
      lymphocytes.
AB  - CD45 is the most common protein tyrosine phosphatase (PTPase) in the membrane of
      white blood cells, serving as a potent regulator of lymphocyte activation and
      signal transduction. While the amino acid sequence of the intracellular domain of
      the molecule is conserved, that of the extracellular domain occurs in multiple
      isoforms, each of the result of alternative mRNA splicing. In T lymphocytes, the
      lowest relative molecular mass (Mr) form, CD45RO, is associated with acquisition
      of memory function, whereas the highest Mr isoform, CD45RA, occurs in "naive" T
      cells. Recently, B cells were also found to express CD45RO following in vitro
      activation. In order to more fully characterize the expression of CD45 on
      activated B cells, we have studied its appearance on Epstein-Barr virus
      transformed (EBV-t) cells and have found heterogeneous expression of CD45RO and
      CD45RA. CD45RO expression was unstable with eventual loss by some EBV-t lines,
      and loss followed by reappearance in others. CD45RA and CD45RO varied
      independently whereas CD45 remained stable and high, suggesting a fluctuation in
      other CD45 isoforms. Immunostaining for CD45RB indicates that a probable 190-kDa
      isoform may be responsible for this observation. A similar bidirectional
      reversible shifting between CD45RA and CD45RO on T-cell lines has also been
      reported by Rothstein et al. In contrast to some reports on normal B cells,
      neither CD45RA nor CD45RO expression was associated with PCA-1 expression.
      Further evidence that these EBV-t lines may not correspond to a well-defined
      stage of B-cell differentiation is provided by the observation that a
      disproportionate loss of CD20 compared to CD19 was noted for several lines. The
      basis for the CD45 isoform switching, or any functional difference(s) in the
      expressed isoforms, is not yet known for human B cells.

PMID- 1370261
TI  - Two-color flow cytometric analysis of thymic lymphocytes from patients with
      myasthenia gravis and/or thymoma.
AB  - Phenotypic characteristics of lymphocyte components of the thymus were determined
      by two-color flow cytometry using monoclonal antibodies to T cell-differentiation
      antigens and activation antigens, and B cells in eight myasthenia gravis (MG)
      thymuses and eight thymomas including four associated with MG to clarify the
      roles of thymus in the diseases. Fifteen normal thymuses and four thymuses from
      non-MG patients were used as controls. Phenotypes of lymphoid components in
      thymoma resembled those in normal thymuses, in which the majority of lymphoid
      cells were immature (common) thymocytes (CD4+CD8+ or CD1+CD3-). The proportions
      of immature thymocytes, however, were relatively higher and those of mature
      thymocytes (CD4+CD8-, CD4-CD8+, CD1-CD3+ or CD2+CD3+) were lower in thymomas than
      normal thymuses. The results speculate that functions which support further
      differentiations of immature thymocytes into mature thymocytes are deficient in
      neoplastic epithelial cells of thymoma. In thymomas, therefore, occasional T
      cells might escape from the thymic surveillance system which eliminates auto
      reactive T cells. Between thymomas associated with MG and those without, however,
      no significant difference was found in the proportions of thymocytes at various
      stages of maturation. In nonthymomatous thymuses from MG patients, an increase of
      both B cells (CD2-DR+ or CD2-CD21+) and activated T cells (CD2+DR+ or CD2+IL-2R+)
      was observed. Furthermore, immature thymocytes were significantly decreased and
      mature thymocytes were increased in the MG thymuses, as compared with normal
      thymuses, non-MG thymuses, and thymomas. These alterations were relevant to the
      histological findings observed in MG thymuses such as thymic involutions and
      germinal center formations: decreased immature thymocytes are considered to
      reflect thymic involutions, while germinal centers, in which lymphocytes from
      peripheral lymphoid organs are activated, are responsible for the increase of B
      cells, activated T cells, and mature T cells. In conclusions, our results suggest
      that neoplastic epithelial cells of thymomas are functionally deficient and that
      MG thymuses are immunologically active and resemble peripheral lymphoid organs.

PMID- 1370262
TI  - The role of tumor necrosis factor in sepsis.
AB  - There is an increasing incidence of sepsis among hospitalized patients. Also,
      high mortality associated with sepsis and septic shock persists despite
      appropriate antibiotic therapy. Recent investigations have demonstrated that
      bacterial antigens stimulate a cascade of cellular mediators or cytokine release.
      In sepsis and septic shock the response of these cytokines often exceeds natural
      downregulation and leads to multisystem organ failure and even death in an
      unacceptably high number of patients. Many investigative studies have shown that
      tumor necrosis factor (TNF) is the prime mediator of the inflammatory response
      seen in sepsis and septic shock. Sepsis management in the future will include
      immune modulating therapy directed against the deleterious effects of cytokines,
      specifically TNF. This article reviews the current problem of sepsis and the
      evidence to support the role of TNF in sepsis. also, recent studies employing
      monoclonal antibodies against TNF as well as considerations for future studies
      are discussed.

PMID- 1370263
TI  - Interferons: pleiotropic cellular modulators.
AB  - Interferons play a key role in host response as pleiotropic modulators of cell
      function. As induced proteins, interferons contrast with other physiologic
      regulators such as glucocorticoids which are produced relatively continuously.
      Antitumor effects have been suggested to be principally the result of two
      mechanisms: a direct effect on the functional capacity or antigenic composition
      of tumor cells or an indirect effect on modulation of immunological effector cell
      populations with tumor specificities. Over the past decade, interferons have been
      established as therapeutically useful molecules for malignant and viral diseases.

PMID- 1370265
TI  - Bleomycin-induced pulmonary function abnormalities.
AB  - The usefulness of serial PFTs in identifying patients who are developing BIP was
      assessed in 59 men with non-seminomatous testicular carcinoma. The mean age was
      27.7 years and all the patients received a standard three-course chemotherapy
      regimen consisting of vinblastine, bleomycin, and cis-diamminedichloroplatinum.
      The average dose of bleomycin was 555.5 units. Serial PFTs, chest roentgenograms,
      and medical assessments were done prior to each course of bleomycin. Nine (15.3
      percent) patients developed pulmonary symptoms due to bleomycin and 23 (39
      percent) had significant changes on chest x-ray films. The Dsb dropped
      significantly with bleomycin treatment; therefore, it is the most sensitive
      indicator of pulmonary response to bleomycin. However, the Dsb failed to
      differentiate patients with BIP from those without. The TLC was found to be a
      much more specific indicator of BIP because reduction in TLC correlated with the
      development of pulmonary symptoms and roentgenologic changes.

PMID- 1370264
TI  - Recombinant human granulocyte-colony-stimulating factor in the treatment of
      patients with neutropenia.
AB  - The results of an open-label, randomized, Phase III trial of r-methionyl human
      granulocyte-colony-stimulating factor (r-metHuG-CSF) in 41 patients with severe
      chronic neutropenia (SCN) are reported. Patients with diagnoses of congenital,
      cyclic, and idiopathic neutropenia, with histories of recurrent infections, were
      evaluated. The primary objective of the trial was to evaluate the ability of r
      metHuG-CSF to increase the ANC to greater than 1500/mm3. A secondary objective
      was to evaluate variables associated with infection-related morbidity in SCN. r
      metHuG-CSF treatment consisted of 1 month of dose titration followed by 4 months
      of treatment at an optimal dose. Patients were randomized to either immediate
      treatment with r-metHuG-CSF (Group A) or four months of observation followed by r
      metHuG-CSF treatment (Group B). r-metHuG-CSF was administered by daily,
      subcutaneous injection with initial doses of 3 to 10 micrograms/kg/day. Forty of
      41 patients who received r-metHuG-CSF had a complete response (median ANC greater
      than 1500/mm3 during 4 months of r-metHuG-CSF treatment). All cases of gingivitis
      and severe mouth ulcers resolved upon treatment with r-metHuG-CSF. Serious
      infections were also eliminated. Only one patient failed to show clinical
      improvement in response to r-metHuG-CSF treatment. Adverse reactions during the
      first 5 months of treatment were mild. Splenomegaly (mild) was noted in some
      patients. The administration of r-metHuG-CSF in patients with SCN significantly
      increased the ANC (P less than 0.001) and was accompanied by a marked reduction
      in infectious complications.

PMID- 1370266
TI  - Diabetes education in a Mexican-American population: pilot testing of a research
      based videotape.
AB  - A diabetes education videotape was designed and pilot tested in a sample of 30
      Spanish-speaking Hispanic diabetic adults in a rural Texas-Mexico border
      community. The videotape provided an overview of diabetes, with emphasis on the
      concept of blood glucose; relationships between food, medications, exercise, and
      blood glucose levels; and blood glucose monitoring. Outcomes of videotape
      effectiveness were based on a 20-item knowledge test and interview data to assess
      acceptability of videotapes as a learning tool. Comparison of the knowledge test
      scores of the experimental group (those who viewed the tape before taking the
      knowledge test) with the control group (those who took the test before viewing
      the tape) produced a positive, moderate effect size of 0.61. Interviews with
      subjects indicated enthusiastic acceptance of the videotape as a means of
      transmitting diabetes information.

PMID- 1370267
TI  - Factors influencing DNA migration from individual cells subjected to gel
      electrophoresis.
AB  - Alkaline and neutral gel electrophoresis of individual mammalian cells allows
      detection of DNA single- and double-strand breaks, respectively. For both the
      alkaline and the neutral assays, lysis conditions influence how much DNA
      migrates, and factors in addition to DNA size play a role in migration. In
      particular, the tight packing of DNA in individual nuclei appears to reduce the
      ability to detect double-strand breaks in all of the genome. Tangling of DNA
      molecules is probably also responsible for the presence of "wings" associated
      with each nucleus after application of pulsed-field gel electrophoresis; these
      wings were aligned in the directions of the pulsed field, not along the resultant
      vector of the fields as was expected. The choice of fluorescent staining methods
      (propidium iodide, Hoechst 33342, or antibodies against bromodeoxyuridine) did
      not influence sensitivity for detecting DNA damage.

PMID- 1370268
TI  - Expression of c-kit protooncogene is stimulated by cAMP in differentiated F9
      mouse teratocarcinoma cells.
AB  - Protooncogene c-kit, a transmembrane tyrosine kinase receptor, was recently shown
      to map to the dominant white spotting locus (W) of the mouse. W mutations affect
      melanogenesis, gametogenesis, and hematopoiesis during development and in adult
      life. In order to determine the regulation of the c-kit gene in cell
      differentiation, we investigated its expression during the differentiation of F9
      cells. Undifferentiated F9 cells and F9 cells treated with retinoic acid (RA)
      alone or dbcAMP alone showed little expression of c-kit mRNA if any. The
      subsequent addition of dbcAMP to F9 cells treated with RA markedly increased the
      expression of c-kit mRNA. Furthermore, the effect of dbcAMP on c-kit expression
      is reversible. In differentiated cells treated with RA, c-kit gene expression is
      induced by agents such as forskolin or theophylline, which are known to elevate
      cellular cAMP level. These results indicate that the expression of the c-kit gene
      is regulated by the level of intracellular cAMP in differentiated F9 cells
      induced by RA.

PMID- 1370269
TI  - Nucleotide sequences of two adjacent M or M-like protein genes of group A
      streptococci: different RNA transcript levels and identification of a unique
      immunoglobulin A-binding protein.
AB  - M protein is a key virulence factor present on the surface of group A
      streptococci. M protein is defined by its antiphagocytic function, whereas M-like
      proteins, while structurally related to M proteins, lack an established
      antiphagocytic function. Group A streptococci can be divided into two main groups
      (class I and II) on the basis of the presence or absence of certain antigenic
      epitopes within the M and M-like molecules, and importantly, the two classes
      correlate with the disease-causing potential of group A streptococci. In an
      effort to better understand this family of molecules, a 2.8-kb region containing
      the two M protein-like genes from a class II isolate (serotype 2) was cloned and
      sequenced. The two genes lie adjacent to one another on the chromosome, separated
      by 211 bp, and have many structural features in common. The emmL2.1-derived
      product (ML2.1 protein) is immunoreactive with type-specific antiserum, a
      property associated with M proteins. The cloned product of the downstream gene,
      emmL2.2 (ML2.2 protein), is an immunoglobulin A (IgA)-binding protein, binding
      human myeloma IgA. Interestingly, the RNA transcript levels of emmL2.1 exceed
      that of emmL2.2 by at least 32-fold. Northern (RNA) hybridization and primer
      extension studies suggest that the RNA transcripts of emmL2.1 and emmL2.2 are
      monocistronic. The ML2.1 and ML2.2 proteins exhibit 53% amino acid sequence
      identity and differ primarily in their amino termini and peptidoglycan-spanning
      domains and in a Glu-Gln-rich region present only in the ML2.1 protein. However,
      the previously described M-like, IgA-binding protein from a serotype 4 isolate
      (Arp4) displays a higher level of amino acid sequence homology with the ML2.1
      molecule than with the IgA-binding ML2.2 protein. Amino acid sequence alignments
      between all M and M-like proteins characterized to date suggest the existence of
      two fundamental M or M-like gene subclasses within class II organisms,
      represented by emmL2.1 and emmL2.2. In addition, IgA-binding activity can be
      found within both types of molecules.

PMID- 1370270
TI  - A 34- to 38-kilodalton Cryptococcus neoformans glycoprotein produced as an
      exoantigen bearing a glycosylated species-specific epitope.
AB  - Three monoclonal antibodies (MAbs), all of the immunoglobulin G1 subclass, were
      raised against Cryptococcus neoformans by using the technique of cyclophosphamide
      ablation of B-cell responses against shared epitopes of the cross-reactive fungus
      Trichosporon beigelii. MAb 3C2 was reactive against the encapsulated and
      nonencapsulated isolates of C. neoformans var. neoformans by enzyme-linked
      immunosorbent assay (ELISA) and Western blot (immunoblot), and in addition to a
      34- to 38-kDa determinant, it recognized a series of lower-molecular-weight
      species. 3C2 also reacted strongly with culture supernatant preparations of C.
      neoformans var. neoformans by ELISA. 3C2 showed no recognition of either T.
      beigelii or C. neoformans var. gattii antigens. Enzymatic deglycosylation
      followed by reaction with 3C2 on Western blots revealed that sialic acid was an
      integral part of the determinant, together with N-acetylglucosaminyl-asparagine
      and alpha-mannose. Proteolytic digestion showed that the epitope was pepsin
      sensitive and that it also contained tryptophan and glycine and/or leucine as
      determinants of recognition by 3C2. The pI of the glycoprotein was 7.1. Affinity
      chromatography-purified antigen did not exhibit proteolytic activity on sodium
      dodecyl sulfate-polyacrylamide substrate gels. Indirect fluorescence antibody
      tests revealed that 3C2 labelling was confined to the cell membrane and cytoplasm
      of yeasts. The remaining MAbs, 7H4 and 5G5, recognized both capsulated and
      nonencapsulated strains of C. neoformans var. neoformans by both ELISA and
      Western Blot, identifying linear determinants with molecular masses of 36 and 30
      kDa. They were unreactive against culture supernatant antigen (exoantigen) from
      either variant of C. neoformans.

PMID- 1370271
TI  - Protection against malaria in Aotus monkeys immunized with a recombinant blood
      stage antigen fused to a universal T-cell epitope: correlation of serum gamma
      interferon levels with protection.
AB  - The major surface antigen p190 of the human malaria parasite Plasmodium
      falciparum contains nonpolymorphic, immunogenic stretches of amino acids which
      are attractive components for a subunit vaccine against malaria. One such
      polypeptide, termed 190L, is contained in the 80-kDa processing product of p190,
      which constitutes the major coat component of mature merozoites. We report here
      that immunization of Aotus monkeys with 190L gives only poor protection against
      P. falciparum challenge. However, addition by genetic engineering of a universal
      T-cell epitope (CS.T3) to 190L improved immunity, and as a result three of four
      monkeys were protected following challenge infection with blood-stage parasites.
      Neither antibody against the immunizing antigens or against blood-stage parasites
      nor the capacity of the monkeys' sera to inhibit in vitro parasite invasion
      correlated with protection. However, in contrast to sera from nonprotected
      monkeys, sera from protected animals contained elevated levels of gamma
      interferon. These results suggest that gamma interferon is directly or indirectly
      involved in the process of asexual parasite control in vivo.

PMID- 1370273
TI  - Tissue-type plasminogen activator-mediated activation of plasminogen on the
      surface of group A, C, and G streptococci.
AB  - The interaction of Glu-plasminogen with group A, C, and G streptococci and
      subsequent formation of surface-associated plasminogen by tissue-type plasminogen
      activator (t-PA) were studied. Binding of 125I-Glu-plasminogen to streptococci
      greatly facilitated its activation to 125I-Glu-plasmin by exogenous t-PA, whereas
      activation in the absence of bacteria took place only slowly. Glu-plasmin formed
      on the streptococcal surface was further converted to the Lys form. Similar
      activation and modification took place also in the presence of plasminogen
      depleted plasma, containing functional t-PA and plasmin inhibitors, indicating
      that the surface-associated enzymes were protected against these inhibitors. Lys
      plasminogen was 10- to 30-fold more potent than Glu-plasminogen or Glu-plasmin in
      inhibiting the binding of 125I-Glu-plasminogen to streptococci. This indicated a
      higher affinity of the Lys form towards plasminogen-binding molecule(s) on the
      streptococcal surface. The surface-associated plasmin was also enzymically active
      as judged by digestion of chromogenic substrate S-2251. Surface-associated
      plasmin activity was observed only when the incubations were carried out in the
      presence of t-PA and Glu-plasminogen or human plasma as the source of
      plasminogen. Under these conditions, soluble enzymatic activity was also
      recovered in the supernatant of group A streptococci. This favors the idea that
      plasmin can be released from the bacterial surface. The findings provide a
      mechanism for streptococci to adopt proteolytic activity by binding a host
      derived enzyme zymogen on their surface, where the subsequent activation then
      takes place. The results suggest a role for surface-associated plasmin activity
      in tissue tropism and tissue invasiveness of streptococci.

PMID- 1370272
TI  - Decreased metabolism and viability of Mycoplasma hominis induced by monoclonal
      antibody-mediated agglutination.
AB  - Monoclonal antibodies (MAbs) were generated against lysates of clinical
      Mycoplasma hominis isolates. Three of these, designated BG2, BA10, and FE6,
      recognized an integral membrane protein of M. hominis with an apparent molecular
      weight of 50,000 (p50). Electron microscopy studies demonstrated that this
      protein is distributed evenly over the cell surface. These anti-p50 MAbs were
      species specific for M. hominis; they reacted with 42% of 126 tested clinical M.
      hominis isolates and showed no reactivity to heterologous mycoplasma species.
      Immunoblot analysis after limited proteolysis of purified p50 demonstrated that
      the three MAbs reacted with different epitopes of the protein. Unlike BA10 and
      FE6, MAb BG2 induced a decrease in arginine metabolism and a reduction of CFU in
      metabolic inhibition tests. F(ab)2 fragments of MAb BG2 showed the same
      inhibitory effect as the intact MAb molecule, while Fab and Fc fragments had no
      influence on vital functions. Preincubation of the mycoplasmas with MAb BG2
      followed by trypsin treatment yielded the same amount of CFU as the control
      without antibodies. In conclusion, the cell aggregates were resolved by the
      trypsin treatment. These experiments and tests with the antibody fragments led to
      the conclusion that only the intact MAb structure or the F(ab)2 structure had
      metabolic inhibition potential and that the observed metabolism inhibition as
      well as the apparent decrease in viability were a result of agglutination by MAb
      BG2.

PMID- 1370275
TI  - Immunochemical studies and complete amino acid sequence of the streptokinase from
      Streptococcus pyogenes (group A) M type 12 strain A374.
AB  - The complete amino acid sequence of the streptokinase (SKase) of Streptococcus
      pyogenes M type 12 strain A374, isolated from a patient with poststreptococcal
      glomerulonephritis (PSGN), was determined. The epitope domain for the monoclonal
      antibody N-59, which cross-reacts with SKases of both the PSGN-associated strain
      and S. equisimilis H46A (a non-PSGN-associated strain), was predicted to be
      localized in residues 370 to 374. The epitope domain specific for monoclonal
      antibody RU-1, which reacts only with the PSGN-associated SKase, was localized to
      residues 164 to 236.

PMID- 1370274
TI  - Roles of protein kinase C and G proteins in activation of murine resting B
      lymphocytes by endotoxin-associated protein.
AB  - Endotoxin-associated protein (EP) from the outer membrane of gram-negative
      bacteria is a potent immunomodulator. To examine the mechanism of EP stimulation,
      the protein kinase C inhibitors H7 and staurosporine were used. Both DNA and RNA
      synthesis of EP-stimulated murine resting B cells were completely inhibited when
      inhibitors were added at 0 h, whereas 55 to 76% inhibition of DNA synthesis was
      observed when H7 was added after 12 h of stimulation. In contrast, HA 1004, which
      blocks protein kinase A and protein kinase G activity, was relatively ineffective
      even at high concentrations, suggesting that the activity of protein kinase C is
      a primary mechanism of EP-induced murine B-cell proliferation. To examine the
      role of G proteins in EP-induced DNA synthesis in B cells, the effects of
      pertussis toxin (PT), which inactivates certain G proteins, and the B oligomer of
      PT (PTB), which does not, were also examined. PT was found to inhibit EP-induced
      DNA synthesis in a dose-dependent manner. However, PTB also caused equivalent
      inhibition, suggesting that PTB may be responsible for most of the inhibitory
      effect seen with the holotoxin. These results serve to question whether G
      proteins are involved in the signal transduction that occurs during EP-induced
      DNA synthesis in murine B cells.

PMID- 1370276
TI  - Protection against Brucella melitensis or Brucella abortus in mice with
      immunoglobulin G (IgG), IgA, and IgM monoclonal antibodies specific for a common
      epitope shared by the Brucella A and M smooth lipopolysaccharides.
AB  - Mice passively immunized prior to a challenge infection with immunoglobulin G
      (IgG) and IgM monoclonal antibodies (MAbs) specific for a common epitope of both
      A- and M-dominant strains had viable Brucella abortus 544 or Brucella melitensis
      H38 counts in the spleen reduced to the same extent as did mice passively
      immunized with MAbs specific for either the A or the M epitope. The IgA MAb was
      not effective.

PMID- 1370277
TI  - Prognostic B-cell epitopes on the flagellar protein of Borrelia burgdorferi.
AB  - Overlapping decapeptides based on the flagellin sequence of Borrelia burgdorferi
      B31 (G. S. Gassmann, M. Kramer, U. B. Gobel, and R. Wallich, Nucleic Acids Res.
      17:3590, 1989) were used to identify immunologically reactive regions of
      flagellin. Five serum specimens from patients with late manifestations of Lyme
      disease and borrelia-specific monoclonal antibody H9724 reacted with an epitope
      in the central region of the flagellar protein (amino acids 205 to 226), which is
      heterologous to the amino acid sequences of other bacterial flagellins. This
      epitope was not recognized by human sera with antibodies to Treponema pallidum,
      sera of healthy individuals, or sera from patients with stage I or II of Lyme
      disease.

PMID- 1370278
TI  - Characterization of I/F1 glycoprotein as a receptor for Mycoplasma pneumoniae.
AB  - Serologic evidence of anti-I and anti-Fl cold agglutinins occurring in mycoplasma
      infections led to the isolation of I/Fl glycoprotein from human erythrocyte
      membranes. Mycoplasma pneumoniae bound to purified I/Fl glycoprotein in a dose
      dependent fashion depending on sialylated carbohydrate determinants. This was
      shown by the decreased binding of mycoplasmas to either sialidase-treated I/Fl
      glycoprotein (dot blot analysis) or sialidase-treated erythrocytes
      (hemagglutination test). Structural properties of the receptor for optimal
      binding could be explored by hemagglutination inhibition assays. Glycophorins
      were excluded as receptors. These results indicate that Fl (and I) antigens are
      receptors for M. pneumoniae.

PMID- 1370279
TI  - Expression of the C3d-binding protein (CR2) from Candida albicans during
      experimental candidiasis as measured by lymphoblastogenesis.
AB  - The complement C3d-binding protein (CR2) of Candida albicans has been purified by
      immunoaffinity chromatography, and its specificity has been characterized by
      immunoblotting with monoclonal antibodies to the C. albicans CR2 and the
      mammalian CR2. Recent studies with immunoelectron microscopy indicated that the
      CR2 was expressed during a systemic infection in a murine model of candidiasis.
      As a continuation of these observations, the immunogenicity of the C. albicans
      CR2 was investigated in a lymphoblastogenesis assay. Lymph node cells as well as
      splenic lymphocytes from mice infected subcutaneously with viable blastoconidia
      of C. albicans reacted to the C. albicans CR2 to a significantly greater extent
      than did lymphocytes from uninfected mice (P less than 0.01). The maximum
      stimulation of splenic lymphocytes by the purified receptor occurred at a
      concentration of 0.54 micrograms of protein per ml after 72 h of incubation of
      lymphocytes and receptor. Also, splenocytes from infected or CR2-immunized mice
      exhibited significantly reduced responses to the T-cell-dependent mitogen
      phytohemagglutinin (P less than 0.01). These data indicate that lymphocytes from
      infected mice respond to the C. albicans CR2 in a lymphoproliferation assay to a
      greater extent than do lymphocytes from uninfected mice, indicating that the CR2
      is expressed in vivo.

PMID- 1370280
TI  - Genetics of xanthan production in Xanthomonas campestris: the xanA and xanB genes
      are involved in UDP-glucose and GDP-mannose biosynthesis.
AB  - The nucleotide sequence of a 3.4-kb EcoRI-PstI DNA fragment of Xanthomonas
      campestris pv. campestris revealed two open reading frames, which were designated
      xanA and xanB. The genes xanA and xanB encode proteins of 448 amino acids
      (molecular weight of 48,919) and 466 amino acids (molecular weight of 50,873),
      respectively. These genes were identified by analyzing insertion mutants which
      were known to be involved in xanthan production. Specific tests for the
      activities of enzymes involved in the biosynthesis of UDP-glucose and GDP-mannose
      indicated that the xanA gene product was involved in the biosynthesis of both
      glucose 1-phosphate and mannose 1-phosphate. The deduced amino acid sequence of
      xanB showed a significant degree of homology (59%) to the phosphomannose
      isomerase of Pseudomonas aeruginosa, a key enzyme in the biosynthesis of
      alginate. Moreover, biochemical analysis and complementation experiments with the
      Escherichia coli manA fragment revealed that xanB encoded a bifunctional enzyme,
      phosphomannose isomerase-GDP-mannose pyrophosphorylase.

PMID- 1370281
TI  - Cloning, nucleotide sequencing, and expression in Escherichia coli of a Rhizobium
      leguminosarum gene encoding a symbiotically repressed outer membrane protein.
AB  - We describe the cloning of a gene from Rhizobium leguminosarum biovar viciae
      strain 248 encoding protein IIIa, the 36-kDa outer membrane protein forming a
      part of the outer membrane protein antigen group III. The expression of this
      antigen group is repressed in the bacteroid form during symbiosis (R. A. de
      Maagd, R. de Rijk, I. H. M. Mulders, and B. J. J. Lugtenberg, J. Bacteriol.
      171:1136-1142, 1989). A cosmid clone expressing the strain 248-specific MAb38
      epitope of this antigen group in a nonrelated strain was selected by a colony
      blot assay. Sequencing revealed one large open reading frame encoding a 39-kDa
      protein. N-terminal amino acid sequencing of the purified 36-kDa outer membrane
      protein IIIa revealed that the isolated gene, now designated ropA, is the
      structural gene for this protein and that the mature protein was formed by
      processing of the 22-residue N-terminal signal sequence. The gene is preceded by
      a promoter that was active in R. leguminosarum but not in Escherichia coli. This
      promoter, which showed no homology to known promoter sequences, was located
      approximately by determination of the transcription start site. The region
      upstream of the putative promoter was shown to contain two potential binding
      sites for integration host factor protein. Expression of protein IIIa under
      control of the inducible lac promoter in E. coli shows that, of its earlier
      described properties, the peptidoglycan linkage of protein IIIa is specific for
      R. leguminosarum but that outer membrane localization and calcium-stabilized
      oligomer formation can to a large extent also occur in E. coli.

PMID- 1370283
TI  - Location of the basal disk and a ringlike cytoplasmic structure, two additional
      structures of the flagellar apparatus of Wolinella succinogenes.
AB  - The basal body of Wolinella succinogenes consists of a central rod, a set of two
      rings (L and P rings), a basal disk from 70 to 200 nm in diameter, and a terminal
      knob. In negatively stained preparations of flagellar hook-basal body complexes,
      some disks remain fixed perpendicularly to the grid and show that such a disk is
      located on the distal side of the P ring. The basal disks have been isolated with
      and without the P ring; in both cases there is a hole in the center of the disk.
      The diameter of the disk is smaller in the presence of the P ring. The L-P ring
      complex is therefore assumed to be a bushing for the rod. Thin sections of whole
      bacteria and spheroplasts reveal that the disk is attached to the inner surface
      of the outer membrane. At the insertions of the flagellar hook-basal body-basal
      disk complexes, depressions are visible in negatively stained preparations of
      whole bacteria and spheroplasts. A new ringlike structure is connected to an
      elongation of the basal body into the cytoplasm in both preparations. Its
      diameter (60 nm) is larger than that of the M ring. A heavily stained compartment
      can be seen in between the new ringlike structure and the basal disk, which may
      be formed by the energy transducing units.

PMID- 1370282
TI  - Phylogenetic analysis of the genus Borrelia: a comparison of North American and
      European isolates of Borrelia burgdorferi.
AB  - We have sequenced the 16S rRNA molecules from four species of Borrelia and from
      six isolates of Borrelia burgdorferi via the reverse transcriptase primer
      extension method. The sequences were aligned and evolutionary relationships were
      determined, including the calculation of evolutionary distances and the
      construction of a phylogenetic tree. These analyses demonstrate significant
      divergence among B. burgdorferi isolates, with the European isolates G1 and G2
      residing most distant from the main cluster. Signature nucleotides which
      distinguish B. burgdorferi from all other members of this genus and which
      distinguish the European isolates G1 and G2 from the North American isolates B31,
      Sh-2-82, and 1352 were identified. Finally, Southern blot analyses were performed
      to compare the restriction patterns of the genes coding for rRNA and to relate
      our data to the grouping scheme of Postic et al. (D. Postic, C. Edlinger, C.
      Richaud, F. Grimont, J. Dufresne, P. Perolat, G. Baranton, and P. A. D. Grimont,
      Res. Microbiol. 141:465-475, 1990).

PMID- 1370285
TI  - Lamina, a novel multicellular form of Methanosarcina mazei S-6.
AB  - A novel multicellular form of Methanosarcina mazei S-6 is described. It was
      termed lamina, and it formed during the exponential growth phase when packets or
      single cells were grown in 40 mM trimethylamine and a total concentration of 8.3
      to 15.6 mM Ca2+ and/or Mg2+, in cultures that were not shaken. A distinct
      molecular event represented by the increment in expression and a spatial
      redistribution of an antigen during lamina formation is documented.

PMID- 1370286
TI  - Characterization of lipopolysaccharide fractions and their interactions with
      cells and model membranes.
AB  - The role of the length of the O-antigen polysaccharide side chain of bacterial
      lipopolysaccharide (LPS) in biological and model membrane systems was
      investigated. LPS from Salmonella typhimurium ATCC 14028 was chromatographed on a
      Sephadex G-200 column in the presence of sodium deoxycholate and separated into
      three fractions on the basis of molecular size. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, Western blot (immunoblot), and chemical
      analyses indicated that these fractions differed from each other primarily in the
      number of repeating units in the O-antigen polysaccharide side chain. In a
      biological system fractions 2 and 3 had the same effects to induce mitogenesis in
      murine lymphocytes, but fraction 1 was less effective than the other two
      fractions. In a model membrane system, LPS induced changes in small unilamellar
      vesicles (SUVs) which were measured by changes in the behavior of a fluorescent
      probe, 1,6-diphenylhexa-1,3,5-triene (DPH), and interaction of increasing amounts
      of all LPS fractions with SUVs gradually increased DPH anisotropy. Fractions 2
      and 3 had similar effects on the SUVs as detected by changes in DPH anisotropy,
      while fraction 1 had almost twice as much activity as the other two fractions.
      These results suggest that the polysaccharide side chain of LPS may modulate the
      ability of biologically active lipid A to interact with cells and model
      membranes. In addition, factors other than changes in membrane fluidity may play
      a role in mediating LPS-induced cell activation.

PMID- 1370284
TI  - Purification and some properties of 2-halobenzoate 1,2-dioxygenase, a two
      component enzyme system from Pseudomonas cepacia 2CBS.
AB  - The two components of the inducible 2-halobenzoate 1,2-dioxygenase from
      Pseudomonas cepacia 2CBS were purified to homogeneity. Yellow component B is a
      monomer (Mr, 37,500) with NADH-acceptor reductase activity. Ferricyanide, 2,6
      dichlorophenol indophenol, and cytochrome c acted as electron acceptors.
      Component B was identified as an iron-sulfur flavoprotein containing 0.8 mol of
      flavin adenine dinucleotide, 1.7 mol of iron, and 1.7 mol of acid-labile sulfide
      per mol of enzyme. The isoelectric point was estimated to be pH 4.2. Component B
      was reduced by the addition of NADH. Red-brown component A (Mr, 200,000 to
      220,000) is an iron-sulfur protein containing 5.8 mol of iron and 6.0 mol of acid
      labile sulfide. The isoelectric point was within the range of pH 4.5 to 5.3.
      Component A could be reduced by dithionite or by NADH plus catalytic amounts of
      component B. Component A consisted of nonidentical subunits alpha (Mr, 52,000)
      and beta (Mr, 20,000). It contained approximately equimolar amounts of alpha and
      beta, and cross-linking studies suggested an alpha 3 beta 3 subunit structure of
      component A. The NADH- and Fe(2+)-dependent enzyme system was named 2
      halobenzoate 1,2-dioxygenase, because it catalyzes the conversion of 2-fluoro-, 2
      bromo-, 2-chloro-, and 2-iodobenzoate to catechol. 2-Halobenzoate 1,2-dioxygenase
      exhibited a very broad substrate specificity, but benzoate analogs with electron
      withdrawing substituents at the ortho position were transformed preferentially.

PMID- 1370287
TI  - Antigenic diversity of the S-layer proteins from pathogenic strains of Aeromonas
      hydrophila and Aeromonas veronii biotype sobria.
AB  - The antigenic relatedness of paracrystalline surface array proteins with subunit
      molecular weights of approximately 52,000 from isolates of Aeromonas hydrophila
      and Aeromonas veronii biotype sobria belonging to a single heat-stable serogroup
      was examined. Enzyme-linked immunosorbent assay and immunoblotting with two
      different polyclonal antisera against surface exposed and non-surface-exposed
      epitopes of the S-layer protein from A. hydrophila TF7 showed that the S-layer
      proteins of the mesophilic aeromonads were antigenically diverse. NH2-terminal
      amino acid sequence analysis of four antigenically different proteins showed that
      while the proteins were structurally related, they differed in primary sequence.
      Absorption experiments with heterologous live cells showed that cross-reactive
      epitopes were in non-surface-exposed regions of the S-layer proteins, while
      absorption with homologous live cells showed that the immunodominant epitopes of
      the S-layer protein of strain TF7 were strain specific and exposed on the surface
      of the native, tetragonal array produced by this strain. Proteolytic digestion of
      the TF7 S-layer protein with trypsin, chymotrypsin, or endoproteinase Glu-C
      produced an amino-terminal peptide of approximate Mr 38,000 which was refractile
      to further proteolytic cleavage under nondenaturing conditions. This peptide
      carried the immunodominant surface-exposed region of the protein, and chemical
      cleavage with cyanogen bromide further mapped the portion of these surface
      exposed epitopes to a peptide of approximate Mr 26,000, part of which maps within
      the Mr 38,000 protease-resistant NH2-terminal peptide.

PMID- 1370288
TI  - mRNA analysis of the adc gene region of Clostridium acetobutylicum during the
      shift to solventogenesis.
AB  - By using primer extension analysis, we located the transcription start point of
      the acetoacetate decarboxylase (adc) gene of Clostridium acetobutylicum 90
      nucleotides upstream from the initiation codon with A as the first transcribed
      nucleotide. From this site the promoter structure TTTACT(18 bp)TATAAT was
      identified; it shows high homology to the consensus sequences of gram-positive
      bacteria and Escherichia coli. Northern blot experiments revealed a length of 850
      bases for the transcript of the adc gene. It thus represents a monocistronic
      operon. Transcription of adc was induced by conditions necessary for the onset of
      solvent formation. Induction occurred long before the respective fermentation
      product (acetone) could be detected in the medium. Transcription of the operon
      containing the genes for acetoacetyl coenzyme A:acetate/butyrate:coenzyme A
      transferase (designated ctf) downstream of the adc gene but divergently
      transcribed is also induced by conditions necessary for the onset of solvent
      formation. The length of the respective RNA transcript, 4.1 kb, indicates
      additional coding capacity, since the genes for the two subunits of the coenzyme
      A transferase cover only approximately 1.5 kb. No distinct transcripts for the
      other open reading frames of the adc gene region, ORF1 and ORF2, could be
      detected. Computer analysis indicated that ORF1, which showed significant
      similarity to the alpha-amylase gene of Bacillus subtilis (U. Gerischer and P.
      Durre, J. Bacteriol. 172:6907-6918, 1990), probably is indeed a coding region.
      ORF2, however, does not seem to have a coding function.

PMID- 1370289
TI  - Overexpression in Escherichia coli and functional analysis of a novel PPi
      selective porin, oprO, from Pseudomonas aeruginosa.
AB  - Immediately upstream from and adjacent to the oprP gene, which codes for the
      phosphate-specific porin OprP of Pseudomonas aeruginosa, lies the PR region
      (oprO), which cross-hybridizes with oprP DNA. To determine the function of this
      region, the oprO gene was expressed behind the lactose promoter in Escherichia
      coli, and the resultant OprO protein was purified and reconstituted into planar
      lipid bilayers. OprO formed sodium dodecyl sulfate-stable trimers, cross-reacted
      immunologically with OprP, and, like OprP, formed an anion-specific, phosphate
      selective porin. However, it demonstrated lower affinity for and higher maximal
      conductance of both chloride and phosphate than did the OprP channel. Examination
      by macroscopic conductance inhibition experiments of the affinity of OprO for
      phosphates of different lengths revealed a preference for PPi and
      tripolyphosphate over Pi, suggesting that OprO functioned as a PPi-selective
      polyphosphate channel, in contrast to OprP, which has a marked preference for Pi.

PMID- 1370290
TI  - Identification of elements involved in transcriptional regulation of the
      Escherichia coli cad operon by external pH.
AB  - Expression of the lysine decarboxylase gene (cadA) of Escherichia coli is induced
      upon external acidification. To dissect the molecular mechanisms responsible for
      this regulation, we analyzed a 4.2-kbp region upstream from cadA. DNA sequencing
      revealed two long open reading frames upstream of and on the same strand as cadA.
      One of these, cadB, is 444 codons long and is situated immediately upstream of
      cadA. Transcriptional fusions between fragments upstream of cadA and lacZ,
      Northern (RNA) hybridization, primer extension, and site-directed mutagenesis
      experiments defined a promoter, Pcad, upstream of cadB that was responsible for
      pH-regulated expression of cadA. Upstream of Pcad is an open reading frame, cadC,
      consisting of 512 codons. The predicted amino terminal region of the cadC gene
      product (CadC) resembles the carboxy-terminal domain of prokaryotic
      transcriptional activators involved in environmental sensing. Tn10 insertions
      within or immediately upstream of cadC abolished Pcad activity, suggesting that
      cadC encodes a positive transcription factor. Expression of plasmid-borne cadC in
      the Tn10 mutants restored Pcad activity, while introduction of a plasmid
      expressing truncated CadC resulted in the inability to complement. The presence
      of Pcad on a multicopy plasmid was found to lower expression arising from
      chromosomal Pcad, suggesting that a positive-acting factor is limiting. Our data
      suggests that cadA, cadB, and the acid-inducible Pcad comprise, at least in part,
      the cad operon which is under control of the cadC product.

PMID- 1370291
TI  - The gene for a 4.5S RNA homolog from Mycoplasma pneumoniae: genetic selection,
      sequence, and transcription analysis.
AB  - In an effort to make an inventory of the tRNA genes of Mycoplasma pneumoniae, a
      DNA fragment was found to contain a sequence that can be folded into a hairpin
      structure very similar to that of the 4.5S RNA of Escherichia coli. Recombinant
      plasmids carrying this region were able to complement E. coli strains that were
      deficient in 4.5S RNA. S1 mapping showed that the mature transcript is only 79
      nucleotides long.

PMID- 1370292
TI  - Glutathione monoethyl ester ameliorates caerulein-induced pancreatitis in the
      mouse.
AB  - Studies in animal models suggest that oxygen radicals may be important in the
      pathogenesis of acute pancreatitis. Because glutathione is an essential component
      of the defense against radical-mediated cellular injury, we investigated whether
      pancreatic glutathione content is influenced by inducing acute pancreatitis and
      whether augmenting the intracellular supply of glutathione would alter the course
      of pancreatitis. Caerulein, a decapeptide cholecystokinin analogue, induces acute
      necrotizing pancreatitis in mice when given in high doses (50 micrograms/kg per
      h) over a period of 6 h. The pancreatic glutathione content (total, GSH + GSSG)
      in mice treated with high-dose caerulein fell to 17% of normal within 4 h of
      beginning caerulein and recovered toward normal after discontinuing caerulein
      treatment. Mice treated with glutathione monoethyl ester (20 mmol/kg 1 h before
      caerulein, 10 mmol/kg 3 and 7 h after starting caerulein) were found to have
      blunted depletion of pancreatic glutathione, diminished histologic evidence of
      pancreatitis (necrosis, inflammation, and vacuolization), and lower serum amylase
      values compared with mice treated with caerulein alone. These findings suggest
      that the profound depletion of pancreatic glutathione caused by hyperstimulation
      of the pancreas with caerulein is critically important in the pathogenesis of
      acute caerulein-induced pancreatitis.

PMID- 1370293
TI  - Increased susceptibility of differentiated mononuclear phagocytes to productive
      infection with human immunodeficiency virus-1 (HIV-1).
AB  - Differences in susceptibility to infection of most mononuclear phagocytes with
      HIV-1 are not known. We investigated the relative susceptibility of autologous
      freshly isolated blood monocytes (MN), MN cultured in vitro to allow
      differentiation (CM), and alveolar macrophages (AM) from healthy subjects to
      productive infection with HIV-1. Cells were infected with the macrophage tropic
      strain HIV-1JR-FL and p24 gag antigen levels measured in supernatants by ELISA.
      Freshly isolated MN had negligible levels of p24 in supernatants. In contrast AM
      had peak p24 levels of 4145 +/- 1456 pg/ml, mean +/- SE, and CM 9216 +/- 3118. As
      a measure of entry and extent of reverse transcription, levels of viral DNA in
      infected mononuclear phagocytes were analyzed by quantitative polymerase chain
      reaction (PCR). The data using primers that amplify all transcripts including
      incompletely formed reverse transcripts indicated that differences in entry of
      the virus may contribute to differences in virus production observed with MN, AM,
      and CM. Other primer pairs that detect intermediate and full-length double
      stranded DNA showed that the ability to complete reverse transcription was
      similar among these mononuclear phagocytes. Since the lung is a major site of
      opportunistic infection and noninfectious complications in HIV-1-infected
      individuals, this increase in productive infection with HIV-1 in AM compared with
      MN could contribute to the immunopathogenesis of the lung disorders seen in the
      acquired immunodeficiency syndrome.

PMID- 1370294
TI  - Regulation of xanthine dehydrogenase and xanthine oxidase activity and gene
      expression in cultured rat pulmonary endothelial cells.
AB  - The central importance of xanthine dehydrogenase (XDH) and xanthine oxidase (XO)
      in the pathobiochemistry of a number of clinical disorders underscores the need
      for a comprehensive understanding of the regulation of their expression. This
      study was undertaken to examine the effects of cytokines on XDH/XO activity and
      gene expression in pulmonary endothelial cells. The results indicate that IFN
      gamma is a potent inducer of XDH/XO activity in rat lung endothelial cells
      derived from both the microvasculature (LMVC) and the pulmonary artery. In
      contrast, interferon-alpha/beta, tumor necrosis factor-alpha, interleukin-1 or 
      6, lipopolysaccharide and phorbol myristate acetate have no demonstrable effect.
      The increase in XDH/XO activity requires new protein synthesis. By Northern
      analysis, IFN-gamma markedly increases the level of the 5.0-kb XDH/XO mRNA in
      LMVC. The increase is due, in part, to increased transcription rate of the XDH/XO
      gene. Transcriptional activation does not require new protein synthesis. The
      physiologic relevance of these observations was evaluated by administering IFN
      gamma to rats. Intraperitoneal administration leads to an increased XDH/XO
      activity and XDH/XO mRNA level in rat lungs. In sum, IFN-gamma is a potent and
      biologically relevant inducer of XDH/XO expression; the major site of
      upregulation occurs at the transcriptional level.

PMID- 1370295
TI  - Distribution patterns of extracellular matrix components and adhesion receptors
      are intricately modulated during first trimester cytotrophoblast differentiation
      along the invasive pathway, in vivo.
AB  - Development of the human embryo depends on the ability of first trimester
      cytotrophoblastic stem cells to differentiate and invade the uterus. In this
      process, transient expression of an invasive phenotype is part of normal
      cytotrophoblast differentiation. Morphologically, this process begins when
      polarized chorionic villus cytotrophoblasts form multilayered columns of
      nonpolarized cells, and invade the uterus. Using immunocytochemistry, we compared
      the presence of adhesion receptors and extracellular matrix ligands on
      cytotrophoblasts in villi, cell columns, and the uterine wall. Villus
      cytotrophoblasts, anchored to basement membrane, stained for alpha 6 and beta 4
      integrin subunits and both merosin and A-chain-containing laminin. Nonpolarized
      cytotrophoblasts in columns expressed primarily alpha 5 and beta 1 integrin
      subunits and a fibronectin-rich matrix. Cytotrophoblast clusters in the uterine
      wall stained for alpha 1, alpha 5, and beta 1 integrins, but not for most
      extracellular matrix antigens, suggesting that they interact primarily with
      maternal cells and matrices. Tenascin staining was restricted to stroma at sites
      of transition in cytotrophoblast morphology, suggesting that tenascin influences
      cytotrophoblast differentiation. Our results suggest that regulation of adhesion
      molecule expression contributes to acquisition of an invasive phenotype by
      cytotrophoblasts and provide a foundation for studying pathological conditions in
      which insufficient or excessive trophoblast invasion occurs, such as preeclampsia
      or choriocarcinoma.

PMID- 1370296
TI  - Protective effect of a microtubule stabilizer taxol on caerulein-induced acute
      pancreatitis in rat.
AB  - The effect of taxol, which is a microtubule stabilizer, was examined in a model
      of acute edematous pancreatitis induced in rat by the administration of
      caerulein. Prophylactic administration of taxol ameliorated inhibition of
      pancreatic secretion, increased level of serum amylase, pancreatic edema, and
      histological alterations in this model. Immunofluorescence studies revealed that
      taxol stabilized the arrangement of microtubules by the action of promoting
      tubulin polymerization and prevented inhibition of pancreatic digestive enzyme
      secretion. In isolated rat pancreatic acini, taxol reversed the inhibition of
      amylase secretion induced by supramaximal concentrations of cholecystokinin
      octapeptide and did not affect the binding of cholecystokinin octapeptide to its
      receptor. The results obtained in this study suggest that microtubule
      disorganization is the initiating event in caerulein-induced pancreatitis and
      that the inhibition of pancreatic digestive enzyme secretion by interfering with
      intracellular vesicular transport due to microtubule disorganization causes
      caerulein-induced pancreatitis.

PMID- 1370297
TI  - Autoimmune disease of the ovary induced by a ZP3 peptide from the mouse zona
      pellucida.
AB  - We describe a novel experimental system in mice for the study of ovarian
      autoimmune disease, a condition encountered in women with premature ovarian
      failure. The ovarian autoimmune disease is induced in B6AF1 mice by a 15-amino
      acid peptide (Cys-Ser-Asn-Ser-Ser-Ser-Ser-Gln-Phe-Gln-Ile-His-Gly-Pro-Arg) from
      mouse ZP3, the sperm-binding component of the zona pellucida that surrounds
      growing and mature oocytes. Whereas the peptide induces both T cell and antibody
      responses, adoptive transfer of CD4+ T cell lines derived from affected animals
      causes oophoritis without observable antibodies to the zona pellucida peptide.
      The primacy of the T cell response in the pathogenesis of disease is further
      substantiated by defining oophoritogenic peptides as small as eight amino acids
      (Asn-Ser-Ser-Ser-Ser-Gln-Phe-Gln) that do not elicit an antibody response to the
      full-length ZP3 peptide. The identification of a well characterized peptide as a
      causative agent of autoimmune oophoritis should facilitate understanding of the
      pathogenesis of this T cell-mediated autoimmune disease. Because the proteins of
      the zona pellucida are conserved among mammals (the mouse and human ZP3 proteins
      are 67% identical), this murine model may lead to better understanding of the
      pathogenesis of human autoimmune oophoritis.

PMID- 1370298
TI  - Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent
      diabetes mellitus.
AB  - Insulin-dependent diabetes mellitus (IDDM) is thought to result from the
      autoimmune destruction of the insulin-producing beta cells of the pancreas. Years
      before IDDM symptoms appear, we can detect autoantibodies to one or both forms of
      glutamate decarboxylase (GAD65 and GAD67), synthesized from their respective
      cDNAs in a bacterial expression system. Individual IDDM sera show distinctive
      profiles of epitope recognition, suggesting different humoral immune responses.
      Although the level of GAD autoantibodies generally decline after IDDM onset,
      patients with IDDM-associated neuropathies have high levels of antibodies to GAD,
      years after the appearance of clinical IDDM. We note a striking sequence
      similarity between the two GADs and Coxsackievirus, a virus that has been
      associated with IDDM both in humans and in experimental animals. This similarity
      suggests that molecular mimicry may play a role in the pathogenesis of IDDM.

PMID- 1370299
TI  - Autocrine angiotensin system regulation of bovine aortic endothelial cell
      migration and plasminogen activator involves modulation of proto-oncogene pp60c
      src expression.
AB  - Rapid endothelial cell migration and inhibition of thrombosis are critical for
      the resolution of denudation injuries to the vessel wall. Inhibition of the
      endothelial cell autocrine angiotensin system, with either the angiotensin
      converting enzyme inhibitor lisinopril or the angiotensin II receptor antagonist
      sar1, ile8-angiotensin II, leads to increased endothelial cell migration and
      urokinase-like plasminogen activator (u-PA) activity (Bell, L., and J. A. Madri.
      1990. Am. J. Pathol. 137:7-12). Inhibition of the autocrine angiotensin system
      with the converting-enzyme inhibitor or the receptor antagonist also leads to
      increased expression of the proto-oncogene c-src: pp60c-src mRNA increased 7-11
      fold, c-src protein 3-fold, and c-src kinase activity 2-3-fold. Endothelial cell
      expression of c-src was constitutively elevated after stable infection with a
      retroviral vector containing the c-src coding sequence. Constitutively increased
      c-src kinase activity reconstituted the increases in migration and u-PA observed
      with angiotensin system interruption. Antisera to bovine u-PA blocked the
      increase in migration associated with increased c-src expression. These data
      suggest that increases in endothelial cell migration and plasminogen activator
      after angiotensin system inhibition are at least partially pp60c-src mediated.
      Elevated c-src expression with angiotensin system inhibition may act to enhance
      intimal wound closure and to reduce luminal thrombogenicity in vivo.

PMID- 1370300
TI  - The susceptibility sequence to rheumatoid arthritis is a cross-reactive B cell
      epitope shared by the Escherichia coli heat shock protein dnaJ and the
      histocompatibility leukocyte antigen DRB10401 molecule.
AB  - Immunological responses to bacterial heat shock proteins have been implicated in
      the pathogenesis of arthritis in animals and humans. The predicted amino acid
      sequence of dnaJ, a heat shock protein from Escherichia coli, contains an 11
      amino acid segment that is homologous to the third hypervariable region of the
      human histocompatibility antigen (HLA) DRB10401 (formerly known as HLA Dw4), the
      part of the molecule that carries susceptibility to rheumatoid arthritis. To test
      the biological significance of this finding, we expressed and purified
      recombinant dnaJ (rdnaJ), and determined its immunologic cross-reactivity with
      HLA DRB10401. A rabbit antipeptide antiserum raised against the sequence of the
      third hypervariable region of HLA DRB10401 specifically bound to 'dnaJ, thus
      confirming that a similar sequence is expressed on the bacterial protein. Of
      greater consequence, an antiserum to the 'dnaJ protein recognized not only a
      peptide from the third hypervariable region of HLA DRB10401, but also the intact
      HLA DRB10401 polypeptide. Furthermore, the antibody to 'dnaJ reacted with HLA
      DRB10401 homozygous B lymphoblasts, but not with HLA DRB11501, DRB10101,
      DRB10301, and DRB10701 (formerly known as HLA Dw2, DR 1, DR 3, and DR 7, in the
      same order) homozygous cells. These results demonstrate that exposure to a
      bacterial heat shock protein can elicit antibodies against the rheumatoid
      arthritis susceptibility sequence in the third hypervariable region of HLA
      DRB10401.

PMID- 1370301
TI  - Localization of cystic fibrosis transmembrane conductance regulator in chloride
      secretory epithelia.
AB  - Cystic fibrosis is caused by mutations in the gene coding for the cystic fibrosis
      transmembrane conductance regulator (CFTR). To further our understanding of
      CFTR's function and regulation, we used confocal immunofluorescence microscopy to
      localize CFTR in cells stained with monoclonal antibodies against different
      regions of the protein: the R (regulatory) domain (M13-1), the COOH terminus (M1
      4), and a predicted extracellular domain (M6-4). All three antibodies
      immunoprecipitated a 155-170-kD polypeptide from cells expressing CFTR. Each
      antibody stained HeLa and 3T3 cells expressing recombinant CFTR, but not cells
      lacking endogenous CFTR: HeLa, NIH-3T3, and endothelial cells. For localization
      studies, we used epithelial cell lines that express endogenous CFTR and have a
      cAMP-activated apical Cl- permeability: T84, CaCo2, and HT29 clone 19A. Our
      results demonstrate that CFTR is an apical membrane protein in these epithelial
      cells because (a) staining for CFTR resembled staining for several apical
      membrane markers, but differed from staining for basolateral membrane proteins;
      (b) thin sections of cell monolayers show staining at the apical membrane; and
      (c) M6-4, an extracellular domain antibody, stained the apical surface of
      nonpermeabilized cells. Our results do not exclude the possibility that CFTR is
      also located beneath the apical membrane. Increasing intracellular cAMP levels
      did not change the apical membrane staining pattern for CFTR. Moreover, insertion
      of channels by vesicle fusion with the apical membrane was not required for cAMP
      mediated increases in apical membrane Cl- conductance. These results indicate
      that CFTR is located in the apical plasma membrane of Cl(-)-secreting epithelia,
      a result consistent with the conclusion that Cl TR is an apical membrane chloride
      channel.

PMID- 1370303
TI  - Bulboventricular foramen size in infants with double-inlet left ventricle or
      tricuspid atresia with transposed great arteries: influence on initial palliative
      operation and rate of growth.
AB  - Bulboventricular foramen obstruction may complicate the management of patients
      with single left ventricle. Bulboventricular foramen size was measured in 28
      neonates and infants greater than 5 months old and followed up for 2 to 5 years
      in those patients whose only systemic outflow was through the foramen. The
      bulboventricular foramen was measured in two planes by two-dimensional
      echocardiography, its area calculated and indexed to body surface area. One
      patient died before surgical treatment. The mean initial bulboventricular foramen
      area index was 0.94 cm2/m2 in 12 patients (Group A) in whom the foramen was
      bypassed as the first procedure in early infancy. The remaining 15 patients
      underwent other palliative operations but the bulboventricular foramen continued
      to serve as the systemic outflow tract. There was one surgical death. Six (Group
      B) of the 14 survivors developed bulboventricular foramen obstruction during
      follow-up (mean initial bulboventricular foramen area index 1.75 cm2/m2). The
      remaining eight patients (Group C) did not develop obstruction during follow-up
      and had an initial bulboventricular foramen larger than that in the other two
      groups (mean initial bulboventricular foramen area index 3.95 cm2/m2). All
      patients with an initial bulboventricular foramen area index less than 2 cm2/m2
      who did not undergo early bulboventricular foramen bypass developed late
      obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370304
TI  - Balloon valvuloplasty as palliation in tetralogy.

PMID- 1370302
TI  - Carboxyl-terminal and central regions of human immunodeficiency virus-1 NEF
      recognized by cytotoxic T lymphocytes from lymphoid organs. An in vitro limiting
      dilution analysis.
AB  - Cytotoxic T lymphocytes (CTL) specific for human immunodeficiency virus (HIV)
      proteins have been analyzed in lymphoid organs from seropositive patients.
      Indeed, an active HIV replication coexists with a major CD8+ lymphocytic
      infiltration in these organs. We have shown in a previous report that HIV
      seropositive patients lungs were infiltrated by HIV specific CD8+ lymphocytes. In
      the present report, we show that HIV-specific CTL responses can also be detected
      in lymph nodes and spleens, and were mainly directed against the ENV, GAG, and
      NEF HIV-1 proteins. The primary NEF-specific CTL responses were further
      characterized by epitope mapping. Determination of epitope-specific CTL
      frequencies were performed by limiting dilution analysis. Our results indicated
      that, in addition to the central region of NEF (AA66-148), a new immunodominant
      region is recognized by CTL. This region corresponds to the carboxyl-terminal
      domain of NEF (amino acids 182-206). AA182-206 is recognized in association with
      at least two common human histocompatibility leukocyte antigen (HLA) molecules
      (HLA-A1 and B8), with clonal frequencies of one CTL per 10(-5) to 10(-6) splenic
      lymphocytes. Our data indicate that lymphoid organs may represent a major
      reservoir for in vivo activated HIV-specific CTL. Furthermore, the carboxyl
      terminal domain of NEF was found to be conserved among several HIV strains.
      Therefore, our finding is of interest for further HIV vaccines development.

PMID- 1370305
TI  - Diversity of cell glycoconjugates shown histochemically: a perspective.

PMID- 1370306
TI  - Peripheral distribution of dermatan sulfate proteoglycans (decorin) in amyloid
      containing plaques and their presence in neurofibrillary tangles of Alzheimer's
      disease.
AB  - We used a polyclonal antibody and a mixture of three monoclonal antibodies (MAb),
      all recognizing the protein core of the small dermatan sulfate proteoglycan
      (DSPG) (known as PG-II or decorin) derived from human skin fibroblasts, to
      immunolocalize this molecule in the characteristic lesions in Alzheimer's brain.
      All antibodies demonstrated positive decorin immunostaining in both the amyloid
      deposits of neuritic plaques (NPs) and the filamentous structures within
      neurofibrillary tangles (NFTs). Unlike heparan sulfate proteoglycans (HSPGs),
      which tend to be evenly distributed throughout NPs containing amyloid fibrils,
      decorin was primarily localized to the periphery of the spherically shaped
      amyloid plaques and to the edges of amyloid fibril bundles within the plaque
      periphery. Decorin was also immunolocalized to the paired helical and straight
      filaments within NFTs and to collagen fibrils surrounding blood vessels. The
      unusual distribution of decorin confined to the periphery of amyloid plaques in
      AD brain suggests that this particular PG may play an important role in the
      development of the amyloid plaque.

PMID- 1370307
TI  - Light microscopic morphometric analysis of peroxisomes by automatic image
      analysis: advantages of immunostaining over the alkaline DAB method.
AB  - The feasibility of light microscopic post-embedding immunocytochemistry for
      morphometry of peroxisomes using automatic image analysis was investigated and
      compared with the classical alkaline DAB method. Perfusion-fixed rat liver tissue
      was either embedded in LR White or incubated in the alkaline diaminobenzidine
      (DAB) medium for cytochemical visualization of catalase. Sections from the LR
      White-embedded material were incubated with a monospecific antibody against
      catalase, followed by protein A-gold and silver intensification. Determination of
      peroxisomal volume density in sections of different thickness revealed that the
      values increased with section thickness in DAB-stained sections but were
      unaffected in immunostained preparations. Moreover, the absolute value for volume
      density of peroxisomes, as determined by light microscopy in immunostained
      sections, was quite close to the value obtained by analysis of electron
      microscopic preparations. Finally, morphometric analysis of bezafibrate-induced
      peroxisome proliferation revealed that the ratio of proliferation obtained by
      light microscopy in immunostained sections was very close to the results obtained
      by electron microscopic morphometry. The main advantage of post-embedding
      immunostaining for light microscopic morphometry is that it restricts the
      immunocytochemical reaction product to the surface of the section, thus making it
      independent of section thickness.

PMID- 1370309
TI  - Secretory organelles of Paramecium cells (trichocysts) are not remarkably acidic
      compartments.
AB  - Acridine orange (AO) trapping in conjunction with fluorescence microscopy was
      applied to Paramecium cells. Trichocysts were not labeled when analyzed with an
      image intensification system (as opposed to a lysosomal population). Only with
      increasing intensity of ultraviolet light (UV) did trichocysts (and to some
      extent the cytosol) exhibit orange fluorescence, both effects being paralleled by
      increasing cell damage. Therefore, in comparison with the reported cytosolic pH
      (6.8), trichocysts cannot be considered as essentially acidic compartments. This
      is supported by experiments in vitro, using isolated cortex fragments or isolated
      fractions of membrane-bounded trichocysts (greater than or equal to 90% non
      leaky). Again, during UV illumination orange fluorescence was observed even in
      the absence of ATP and Mg2+. Furthermore, this AO fluorescence and the
      condensation state of trichocyst contents were not affected by NH3 or by any of
      the widely differing ion- and H(+)-exchange inhibitors or ionophores tested.
      Decondensation of trichocyst contents occurred only when Ca2+ ionophore A23187 or
      X537A was incorporated into trichocyst membranes and when Ca2+ was then added. In
      this case all trichocysts partially decondensed within their intact membranes. We
      conclude that AO might be trapped in trichocysts by the abundant acidic secretory
      components during observation with UV light, rather than by acidic luminal pH.

PMID- 1370308
TI  - Alternative staining methods for Lowicryl sections.
AB  - A number of stains and stain combinations have been identified that, when used
      with the hydrophilic resin Lowicryl K11M, produce marked improvements over
      aqueous uranyl and lead salts (UA-Pb) in terms of low granularity, specificity,
      and range of components contrasted. Three test specimens, tobacco mosaic virus
      (TMV), starfish sperm, and cultured mouse fibroblasts, were used to evaluate
      stain characteristics. UA-Pb showed a preference for nuclei acids, which were
      stained specifically by osmium ammine-B at pH 1.5. A number of stain combinations
      in which UA was followed or preceded by salts containing barium, manganese,
      tungsten, molybdenum, and vanadium provided excellent staining of protein
      containing components, each stain combination being unique in terms of the degree
      to which specific components were discriminated. These stains were particularly
      effective for visualizing internal components of the nucleus where a number of
      fibrillar and particulate structures not seen with UA-Pb were well contrasted.

PMID- 1370310
TI  - Biological significance of dermal Merkel cells in development of cutaneous nerves
      in human fetal skin.
AB  - We detected epidermal Merkel cells in 12-week fetuses with monoclonal antibodies
      (MAb) against simple epithelium keratin and epithelial membrane antigen. In 15
      week fetuses these Merkel cells began to descend into the dermis and expressed
      nerve growth factor receptors (NGF-R). At approximately the same time, cutaneous
      nerves, as detected with an MAb against neurofilaments, extended from the
      subcutaneous trunk and branched to form the subepidermal nerve plexus. The
      expression of NGF-R on dermal Merkel cells preceded their connection with
      immunoreactive small nerves. Initially, most of these fine nerve endings were
      directed towards dermal Merkel cells. In 23-week fetuses the subepidermal nerve
      plexus was well developed and immunoreactive dermal Merkel cells began to
      disappear. At all stage of fetal development the epidermal Merkel cells did not
      strongly express NGF-R. We postulate that dermal Merkel cells play an inductive
      and a promotional role in development of the cutaneous nerve plexus in the upper
      dermis.

PMID- 1370311
TI  - Complete dissection of the Hb(64-76) determinant using T helper 1, T helper 2
      clones, and T cell hybridomas.
AB  - We have generated cloned Th1 cells, Th2 cells, and T cell hybridomas specific for
      the single immunogenic peptide from the beta-chain of murine hemoglobin (Hb(64
      76)). The availability of these various types of T cells provided us an unique
      opportunity to examine and dissect the T cell response to an immunogenic peptide.
      A panel of altered Hb peptides was made by replacing each amino acid in the Hb
      peptide (positions 64-76) with a conservative amino acid substitution or an
      alanine. Although none of the eleven T cell clones and hybridomas tested
      exhibited the same pattern of reactivity to the substituted Hb peptides, some
      general features were identified for all T cell responses. The primary T cell
      contact residue of Hb(64-76) was shown to be asparagine 72. For every Hb(64-76)
      specific T cell, no activation was observed using a peptide containing the
      conservative substitution of a glutamine for the asparagine at position 72. The
      flanking glutamic acid at position 73 was also required for a proliferative
      response for all of the Th1 and Th2 clones. The Th subtypes were not grossly
      unique in their responses to the substituted Hb peptides, but exhibited minor
      differences in fine specificity with the Th1 cells identifying more critical
      amino acids then did the Th2 cells. For the Th1 cells and also the T cell
      hybridomas, the phenylalanine at position 71 was critical for a T cell response.
      Analysis of peptide affinity for IEk molecules indicated that position 71 played
      a role in peptide binding to MHC. Secondary T cell contact residues, which were
      important for many but not all of the T cells, were identified at positions 69,
      70, and 76. Overall T cell responses were minimally affected by changes in the
      amino acid residues at positions 64-68, 74, and 75. We have also demonstrated
      that cloned Th1 cells, Th2 cells and T hybridomas can be generated against the
      same Hb(64-76) determinant.

PMID- 1370312
TI  - In vitro maximum binding of antigenic peptides to murine MHC class II molecules
      does not always take place at the acidic pH of the in vivo endosomal compartment.
AB  - Presentation of Ag to the T cell requires binding of specific peptide fragments
      of the Ag to MHC II molecules. The ability of a peptide to bind to MHC class II
      appears to be pH dependent. Recent reports indicate that the binding of peptide
      to MHC class II molecules takes place primarily within an endosomal compartment
      of the cell at around pH 5. In this study, we have explored the in vitro pH
      dependence of peptide binding to different haplotypes of murine MHC class II
      molecules. The binding of peptides to MHC II was analyzed and quantitated by
      silica gel TLC, using radiolabeled peptides. The MBP peptide fragments, MBP(1
      14)A4 and MBP(88-101)Y88, bound maximally at pH 8 to IAk and IAs, respectively.
      The binding of PLP peptide fragment, PLP(138-151)Y138, to IAs was maximal at
      around neutral pH. The maximum binding of an OVA peptide fragment, OVA(323
      340)Y340, to IAd, was found to occur at pH 6. Results presented in this report
      thus suggest that the in vitro maximum binding of peptide is pH dependent and
      does not always occur at pH 5. The optimum pH range for maximum binding may
      depend on the nature and net charge of the peptide and its interaction with MHC
      class II molecules.

PMID- 1370313
TI  - Analysis of the effects of activation of the alternative pathway of complement on
      erythrocytes with an isolated deficiency of decay accelerating factor.
AB  - E from individuals with the Inab blood group phenotype have an isolated
      deficiency of decay accelerating factor (DAF, CD55). DAF is a glycosyl
      phosphatidylinositol anchored membrane protein that inhibits activation of both
      the classical and alternative pathways of complement. Deficiency of DAF from the
      E of paroxysmal nocturnal hemoglobinuria (PNH) is thought to contribute to their
      greater sensitivity to complement-mediated lysis. Unlike PNH E, however, Inab
      cells are not susceptible to acidified serum lysis, a process that is mediated
      through activation of the alternative pathway. This observation led us to
      hypothesize that membrane constituents other than DAF control susceptibility to
      acidified serum lysis. To investigate this hypothesis, Inab E were incubated in
      acidified serum, and hemolysis and C3 deposition (as a measure of alternative
      pathway activation) were quantitated. C3 deposition of Inab cells was
      approximately 20 times greater than normal, however, hemolysis was not observed.
      Inab E expressed a normal amount of membrane inhibitor of reactive lysis (MIRL,
      CD59), a glycosyl phosphatidylinositol anchored protein that is also deficient in
      PNH. When MIRL function was blocked with antibody, C3 deposition markedly
      increased, and 100% of the Inab cells hemolyzed in acidified serum. These studies
      demonstrate that susceptibility to acidified serum lysis is controlled primarily
      by MIRL, and that in addition to its regulatory affect on the membrane attack
      complex, MIRL also modulates the activity of the C3 convertase of the alternative
      pathway by a mechanism that remains to be determined.

PMID- 1370314
TI  - Inhibition of IgE binding to RBL-2H3 cells by a monoclonal antibody (BD6) to a
      surface protein other than the high affinity IgE receptor.
AB  - A mAb was isolated (mAb BD6) that recognized a surface glycoprotein on rat
      basophilic leukemia cells (RBL-2H3). The antibody bound to 2 x 10(6)
      molecules/cell and specifically blocked IgE binding (50% inhibition with 3.48 +/-
      0.51 micrograms/ml; mean +/- SEM), although neither IgE nor anti-high affinity
      IgE receptor (anti-Fc epsilon RI) mAb blocked mAb BD6 binding to the cells. mAb
      BD6 did not affect the rate of dissociation of cell-bound IgE, nor did it induce
      or inhibit the internalization of IgE. mAb BD6 did not release histamine.
      However, it did cause rapid spreading of the cells. By 1 h the cells had
      retracted to a spherical shape with their surface covered with membranous spikes,
      and they could easily be detached from the tissue culture plate. These changes
      differed from those observed after Fc epsilon RI activation. mAb BD6
      immunoprecipitated a complex of two proteins, 38 to 50 kDa and 135 kDa from 125I
      surface labeled rat basophilic leukemia cells that are not subunits of Fc epsilon
      RI. Chemical cross-linking studies showed that these molecules are associated on
      the cell surface. By immunoblotting, mAb BD6 reacted with a 40-kDa protein.
      Therefore, mAb BD6 binds to a surface protein that is close to the Fc epsilon RI
      and sterically inhibits 125I-IgE binding.

PMID- 1370315
TI  - Differential increase of an alternatively polyadenylated mRNA species of murine
      CD40 upon B lymphocyte activation.
AB  - CD40 is an integral membrane glycoprotein found on the surface of human B
      lymphocytes. Antibodies specific for CD40 have been shown to augment
      proliferation of activated B lymphocytes, prevent B lymphocyte apoptosis, and
      prolong the maintenance of normal B lymphocytes in culture. As a step toward
      developing an in vivo system to examine CD40 function, a molecular clone encoding
      the murine homologue of the human CD40 B lymphocyte surface Ag was isolated and
      characterized. Throughout their open reading frames, the murine and human
      proteins shared 62% predicted amino acid identity. Within the cytoplasmic domain,
      which includes a completely conserved region known to be important for signaling
      by human CD40, the CD40 homologues are 78% identical. The human and murine
      proteins are members of a new cytokine receptor family, which includes the
      receptors for nerve growth factor and TNF-alpha, that are homologous in their
      cysteine-rich extracellular domains. The murine CD40 gene is expressed in B
      lymphocytes as two mRNA species generated by alternative usage of polyadenylation
      signals in the 3' untranslated region. The activation of B lymphocytes
      differentially increases the relative levels of these two mRNA transcripts
      suggesting a posttranscriptional mechanism for the regulation of CD40 surface
      expression.

PMID- 1370316
TI  - The in vitro radiosensitivity of lymphocytes from chronic lymphocytic leukaemia
      using the differential staining cytotoxicity (DiSC) assay. I--Investigation of
      the method.
AB  - A tumour sensitivity assay, the differential staining cytotoxicity (DiSC) assay,
      which has been shown to have potential in predicting tumour response to cytotoxic
      drugs, has been developed to investigate the radiosensitivity of peripheral blood
      lymphocytes isolated from patients with chronic lymphocytic leukaemia (CLL). The
      method involved irradiating isolated lymphocytes (0.64-20.48 Gy at 8 x 10(5)
      cells/ml) and incubating for 4 days. Subsequent radiation-induced cell kill was
      assessed by differential staining of dead and live cells and calculation of
      tumour cell viability. Factors affecting assay success rate and in vitro
      radioresponse were investigated. Results were shown to be reproducible both when
      repeat assays were performed on the same specimen on the same day, and on
      different specimens from the same patient after intervening periods of time.
      Greater than 1 day transit time (whole blood) or storage (separated cells in
      medium) was found to be detrimental to assay success, but pH of the medium
      (either pH 7.3 or 8) had little effect. An increased incubation period (from 4 to
      7 days) slightly reduced cell survival, but the underlying radioresponsiveness of
      the cells did not change.

PMID- 1370317
TI  - The in vitro radiosensitivity of lymphocytes from chronic lymphocytic leukaemia
      using the differential staining cytotoxicity (DiSC) assay. II--Results on 40
      patients.
AB  - A tumour sensitivity assay, the differential staining cytotoxicity (DiSC) assay,
      which has been shown to have potential in predicting tumour response to cytotoxic
      drugs, has been used to investigate the radiosensitivity of peripheral blood
      lymphocytes isolated from patients with chronic lymphocytic leukaemia (CLL). The
      isolated lymphocytes were irradiated and incubated for 4 days. Radiation-induced
      cell kill was assessed by differential staining of dead and live cells with
      subsequent calculation of tumour cell viability. The results of 61 CLL specimens
      from 40 patients are reported, showing profound inter-patient differences in the
      sensitivity of cells to radiation. Five patient specimens, which were
      radioresistant in vitro, were from patients who were also resistant clinically to
      irradiation. Another patient who responded very well clinically was found to be
      extremely sensitive in the assay.

PMID- 1370318
TI  - DNA ligands as radioprotectors: molecular studies with Hoechst 33342 and Hoechst
      33258.
AB  - Following earlier reports of radioprotection of cells by Hoechst 33342, we have
      investigated radioprotection of isolated DNA by the minor groove binders Hoechst
      33258 and Hoechst 33342. Analysis of radiation-induced single strand breakage in
      plasmid DNA (pBR322) showed concentration-dependant protection, up to a dose
      modifying factor of 9.3 for 25 microM Hoechst 33258, at which the ligand: bp
      ratio was 0.67. Since the ligands bind at discrete sites along DNA, sequencing
      gel analysis was used to investigate the radioprotective effects of the ligands
      both at and between the ligand-binding sites. These experiments showed that
      although protection was more pronounced at the binding sites, there was also some
      reduction in strand-breakage between binding sites. Detailed analysis at a
      particular site, the EcoR1 site in a 3'-32P-endlabelled 100bp restriction
      fragment from pBR322, showed that protection was most pronounced at the 'inner
      T': GAATTC. Irradiation of a synthetic oligodeoxynucleotide containing a single
      ligand-binding site, and labelled at the 5'-end, gave the expected doublet bands
      in high resolution gels, corresponding to fragments with 3'-phosphoryl- and 3'
      phosphorylglycollate terminii. In the Hoechst 33258-protected sample, the 3'
      phosphorylglycollate band was preferentially suppressed within the binding site.
      These results, together with published crystal structure data for a Hoechst
      33258/dodecamer complex, suggest that the site-specific radioprotection may be
      due to H-atom donation from the benzimidazole NH groups in the ligand to
      radiation-induced radicals on 4'-deoxyribosyl carbons. In contrast to the
      experiments with purified DNA, in which the two ligands yielded similar results,
      Hoechst 33342 was a much more active radioprotector in experiments with intact
      cells. For 20 microM Hoechst 33342, the dose-modifying factor was 1.7 at 1%
      survival and 1.3 at 10% survival, whereas the same level of Hoechst 33258 yielded
      barely detectable protection, perhaps due to a demonstrably lower cellular
      uptake. Presumably the radioprotection of cells by Hoechst 33342 is due to
      suppression of DNA strand breakage, and further investigation of the protection
      mechanism(s) should enable development of improved radioprotectors.

PMID- 1370319
TI  - Characterization of receptors for substance P in human astrocytoma cells:
      radioligand binding and inositol phosphate formation.
AB  - UC11 cells, derived from a human astrocytoma, have a high density of functional
      substance P receptors. Radioligand binding studies were conducted with the highly
      selective neurokinin-1 receptor ligand [3H][Sar9,Met(O2)11]-substance P. Kinetic
      binding experiments conducted at 4 degrees C yielded an association rate constant
      k1 of 1.86 x 10(7) M-1 min-1, a dissociation rate constant k-1 of 0.00478 min-1,
      and a calculated kinetic KD of 257 pM. Saturation binding experiments yielded
      average values of KD = 447 +/- 103 pM, Bmax = 862 +/- 93 fmol/mg of protein. This
      Bmax corresponds to more than 150,000 binding sites/cell. Competition binding
      experiments with unlabeled [Sar9,Met(O2)11]-substance P yielded average values of
      KD = 491 +/- 48 pM and Bmax = 912 +/- 67 fmol/mg of protein. In [3H]inositol
      labeled cells, substance P induced a robust inositol phosphate formation.
      Inositol trisphosphate levels increased as much as 20-fold within approximately
      15 s of addition of substance P. This inositol trisphosphate formation was
      transient and had returned to baseline within the first 60-120 s. Inositol
      monophosphate formation, however, was linear for at least 2 h. Structure activity
      data on binding and inositol monophosphate formation confirmed the presence of a
      neurokinin-1 receptor subtype in these cells. Thus, the UC11 cell should be a
      useful model cell for delineating the physiological role of substance P receptors
      in astrocytes.

PMID- 1370320
TI  - Protein phosphotyrosine in mouse brain: developmental changes and regulation by
      epidermal growth factor, type I insulin-like growth factor, and insulin.
AB  - Using antiphosphotyrosine antibodies, we have investigated protein
      phosphorylation in mouse brain during development in intact animals and in
      reaggregated cerebral cultures. Under basal conditions, in vivo and in vitro, the
      levels of two main phosphoproteins, of Mr 120,000 and 180,000 (pp180), increased
      with development, reaching a maximum in the early postnatal period and decreasing
      thereafter. In adult forebrain, pp180 was still highly phosphorylated, but it was
      not detected in cerebellum or in peripheral tissues. In reaggregated cortical
      cultures, epidermal growth factor (EGF), type I insulin-like growth factor (IGF
      I), and insulin enhanced protein tyrosine phosphorylation of several proteins,
      which were specific for EGF or IGF-I/insulin. In highly enriched neuronal or
      astrocytic monolayer cultures, some proteins phosphorylated in basal conditions,
      or in response to EGF and IGF-I, were found in both types of culture, whereas
      others appeared cell type specific. In addition, in each cell type, some proteins
      were phosphorylated under the action of both growth factors. These results
      indicate that tyrosine protein phosphorylation is maximal in mouse brain during
      development and is regulated by growth factors in neurons as well as in
      astrocytes.

PMID- 1370321
TI  - Cervicothalamic tract terminals are enriched in glutamate-like immunoreactivity:
      an electron microscopic double-labeling study in the cat.
AB  - The distribution of glutamate-like immunoreactivity (Glu-LI) in the thalamic
      ventral posterolateral nucleus (VPL) of cats was studied with the EM immunogold
      technique in order to identify nerve terminal populations that may use glutamate
      as a neurotransmitter. The investigation was focused on cervicothalamic tract
      (CTT) terminals, which were labeled by WGA-HRP transported anterogradely from
      injection sites in the lateral cervical nucleus (LCN). The amount of Glu-LI in
      different profiles was evaluated quantitatively by counting the number of gold
      particles and then calculating the areal density of gold particles over different
      profile types. The highest density of gold particles was found over terminals
      with morphologic characteristics of terminals of cortical origin (RS terminals),
      a finding that further supports the glutamatergic nature of these terminals
      suggested by previous studies. Enrichment of Glu-LI was also found in CTT
      terminals and in non-peroxidase-labeled terminals with the same morphologic
      characteristics as CTT terminals (RL terminals). The labeling density over these
      terminals was about twice the average tissue density of gold particles. The
      labeling density over large VPL neuronal cell bodies was on average 127%, and
      that over vesicle-containing dendritic appendages and truncs (presynaptic
      dendrites) about 80%, of the average tissue density of gold particles. Immunogold
      labeling with antiserum against glutamine (Gln) indicated low levels of Gln-like
      immunoreactivity in CTT terminals and a high Glu:Gln ratio as compared to
      astrocytes and the average Glu:Gln ratio in the VPL. The present findings provide
      further support for a transmitter role of glutamate in terminals of ascending
      somatosensory afferents to the VPL, including the CTT. Taken together with
      previous findings of an enrichment of Glu-LI in terminals of the spinocervical
      tract (Broman et al., 1990), our results suggest that synaptic transmission in
      the spinocervicothalamic pathway is dependent on the release of glutamate both at
      the levels of the LCN and the VPL.

PMID- 1370322
TI  - Modulation by cAMP of a slowly activating potassium channel expressed in Xenopus
      oocytes.
AB  - When expressed in the Xenopus oocyte, the minK protein induces a slowly
      activating voltage-dependent potassium current (Isk). We studied the modulation
      of this current by altering intracellular cAMP levels and found that the
      amplitude of Isk is dramatically increased by treatments that raise cAMP levels
      and decreased by agents that lower cAMP levels. Preinjection of a protein
      inhibitor of the cAMP-dependent protein kinase blocked the effects of increased
      cAMP levels. There were no changes in the voltage dependence or kinetics of Isk.
      Mutations that eliminate a potential phosphorylation site on the minK protein did
      not block the effects of activating the kinase. In addition, the membrane
      capacitance of the oocyte increased and decreased in parallel with Isk. Our
      results fit a mechanism in which channel proteins are selectively inserted into
      and removed from the plasma membrane in response to changes in kinase activity.

PMID- 1370324
TI  - Diffusional transport of macromolecules in developing nerve processes.
AB  - Passive transport of macromolecules in growing nerve processes was analyzed
      quantitatively by measuring the rate of diffusion of fluorescently labeled
      molecules injected into the soma of cultured Xenopus neurons. We found that the
      diffusion of globular proteins in the neurite's cytoplasm was about five times
      slower than that in aqueous solution, a rate considerably higher than those
      inferred from previous studies on cultured non-neuronal cells. The dependence of
      the diffusion coefficient, D, on the size of diffusing molecules was examined by
      measuring the diffusional spread of fluorescently labeled dextrans over a wide
      range of molecular weights. We found that the size dependence of D deviates
      considerably from that expected for diffusion in a viscous aqueous medium: larger
      dextrans encounter disproportionately higher viscous resistance. Treatment of the
      neuron with the microfilament-disrupting agent cytochalasin B, or pre-loading of
      the cells with dephospho-synapsin I, a molecule that induces bundling of actin
      filaments, significantly increased the diffusion rate for large dextrans without
      affecting that of small dextrans. Taken together, these results provide a
      quantitative basis for assessing diffusion as a potential transport mechanism
      along nerve processes, and suggest that the microfilament meshwork imposes a
      selective constraint on the diffusion of large macromolecular components within
      the neuronal cytoplasm.

PMID- 1370323
TI  - Presynaptic calcium signals and transmitter release are modulated by calcium
      activated potassium channels.
AB  - The regulation of synaptic transmission by Ca(2+)-activated potassium (gKca)
      channels was investigated at the frog neuromuscular junction (nmj). Charybdotoxin
      (CTX), a blocker of certain types of gKca channels, induced a twofold increase of
      transmitter release. Similar results were obtained with purified natural toxin,
      synthetic toxin, and recombinant toxin. Apamin, a blocker of a different type of
      gKca channel, did not alter transmitter release. CTX was ineffective after
      intraterminal Ca2+ buffering was increased by application of the membrane
      permeant Ca2+ buffer dimethyl-BAPTA-AM. By itself, the permeant buffer first
      caused a slight increase in transmitter release before release was eventually
      decreased. This increase of release did not occur when the buffer was applied in
      the presence of CTX or Ba2+, another gKca channel blocker. Stimulus-evoked entry
      of Ca2+ in nerve terminals, detected with the fluorescent Ca2+ indicator FLUO-3,
      was increased after blockade of gKca channels by CTX. CTX had no effect on the
      amount or the time course of synaptic depression. The results are consistent with
      the hypothesis that CTX-sensitive gKca channels normally narrow the presynaptic
      action potential and thus, by indirectly regulating Ca2+ entry, can serve as
      powerful modulators of evoked transmitter release. In order to affect presynaptic
      action potentials, the gKca channels must be located close to Ca2+ channels.

PMID- 1370325
TI  - Starch hydrolysis by the ruminal microflora.
AB  - The effects of grain type and processing on ruminal starch digestion are well
      documented but poorly understood at the biochemical and molecular levels. Waxy
      grains have starches high in amylopectin and are more readily digested than
      nonwaxy grains. However, the composition of the endosperm cell matrix and the
      extent to which the starch granules are embedded within it also affect starch
      digestion rates. Continued work is needed to determine the influence of specific
      cell matrix proteins, protein-starch interactions and cell wall carbohydrates on
      starch availability. The microbial populations that metabolize starch are
      diverse, differing in their capacities to hydrolyze starch granules and soluble
      forms of starch. Surveys show that the amylases are under regulatory control in
      most of these organisms, but few studies have addressed the types of amylolytic
      enzymes produced, their regulation and the impact of other plant polymers on
      their synthesis. Research in these areas, coupled with the development and use of
      isogeneic or near-isogeneic grain cultivars with biochemically defined endosperm
      characteristics, will enhance our ability to identify mechanisms to manipulate
      ruminal starch digestion.

PMID- 1370326
TI  - Dietary influences on carbohydrases and small intestinal starch hydrolysis
      capacity in ruminants.
AB  - Data describing the influence of diet composition and intake on amylolytic and
      disaccharidase activities in the ruminant small intestine are reviewed. Changing
      dietary components from forage to grain increased pancreatic alpha-amylase
      activities in most studies; however, when metabolizable energy intake was
      equalized, concentrations of alpha-amylase in the pancreas and the total
      quantities in the small intestinal lumen were greater in forage-fed than in grain
      fed animals. Concentration of pancreatic alpha-amylase increased with dietary
      energy intake. Changing diet composition or metabolizable energy intake exerted a
      small effect on intestinal disaccharidase activities, with hydrolytic capacity
      altered principally through changes in intestinal length. Other studies suggest a
      small contribution of intestinal disappearance of carbohydrates to net portal
      appearance of glucose. The fate of large portions of intestinal carbohydrate
      disappearance have not been adequately defined. For the importance of intestinal
      carbohydrate supply to be understood, the quantity of carbohydrate undergoing
      both enzymatic hydrolysis and absorption must be determined.

PMID- 1370327
TI  - Nuclear zinc uptake and interactions and metallothionein gene expression are
      influenced by dietary zinc in rats.
AB  - Regulation of metallothionein gene expression by dietary zinc and the
      relationship of dietary zinc to nuclear zinc uptake was examined in growing rats.
      Zinc was fed at 5, 30 or 180 mg/kg, either in pelleted form for a 2-wk period (ad
      libitum) or for 2 h as a liquefied preparation (1 g in 4 mL). Two hours after the
      oral dose, the intestine and liver took up more zinc than other tissues. Nuclei
      purified from liver, kidney and spleen accumulated substantial amounts of zinc
      and directly reflected the dietary zinc level within the 2-h feeding period.
      Nuclei from kidney accumulated the largest amount of dietary zinc within 2 h,
      accounting for up to 6.2% of the total nuclear zinc concentration. Northern
      analysis demonstrated that metallothionein expression was proportional to dietary
      zinc intake in some tissues. It was greatest in kidney, followed in descending
      order by liver, intestine, spleen and heart. Thymus and lung metallothionein mRNA
      levels were not changed appreciably by dietary zinc intake. Chromatography of
      extracts from liver nuclei shows that 65Zn introduced into the portal supply is
      bound to discrete fractions of nuclear proteins. One of these fractions binds
      both 65Zn and a 32P-labeled oligonucleotide corresponding to the metal regulatory
      element of the metallothionein promoter. These results demonstrate that
      significant amounts of zinc from the diet are rapidly taken up by cell nuclei.
      Furthermore, they suggest that transcriptional regulation of the metallothionein
      gene and other genes with metal regulatory elements involves a direct interaction
      between the dietary supply and intranuclear factors that bind zinc.

PMID- 1370328
TI  - Re: Prostate specific antigen values after radical retropubic prostatectomy for
      adenocarcinoma of the prostate: impact of adjuvant treatment (hormonal and
      radiation)

PMID- 1370330
TI  - Immunoreactive prostatic specific antigen in male periurethral glands.
AB  - Prostatic specific antigen (PSA) is considered an antigen unique to benign and
      malignant prostatic tissue. Recent evidence in the literature has raised serious
      doubts about the specificity of this antigen. In this study twenty male urethral
      specimens were evaluated for PSA and prostatic acid phosphatase (PAP) from
      patients without evidence of prostatic cancer. Eight of these 20 urethral
      specimens exhibited strong immunostaining for both PSA and PAP, localized in the
      periurethral glands. Five of the 17 urethral biopsies were positive for both
      antigens, while all three of the whole mount autopsy specimens stained positive
      for PSA and PAP. Within the autopsy series, there was heterogenous staining of
      the periurethral glands within the same specimen. This evidence disproves the
      fact that PSA and PAP are organ specific as previously described. More than
      likely any tissue of cloacal origin has potential for staining positive for
      prostatic specific antigen and prostatic acid phosphatase.

PMID- 1370331
TI  - Bladder cancer cells express functional receptors for granulocyte-colony
      stimulating factor.
AB  - The effects of human recombinant granulocyte-colony stimulating factor (G-CSF) on
      the growth of cultured human bladder cancer cells and G-CSF receptor on these
      cells were investigated. Human bladder cancer cell lines, KU-1 or NBT-2, were
      incubated with and without G-CSF. At 48 hours, 3H-thymidine uptake of both cells
      was significantly higher with G-CSF (one ng./ml., 10 ng./ml.) than that of
      control without G-CSF (p less than 0.05). The binding of 125I-labeled KW-2228, a
      muteins of G-CSF, to KU-1 and NBT-2 was inhibited by unlabeled KW-2228 in a dose
      dependent manner. These results demonstrated that G-CSF stimulates the clonal
      growth of human bladder cancer cells by binding to its specific receptors.

PMID- 1370329
TI  - Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus
      cavernosum smooth muscle tone.
AB  - Relaxation of penile corpus cavernosum smooth muscle is controlled by nerve and
      endothelium derived substances. In this study, endothelium-dependent relaxation
      of corporal smooth muscle was characterized and the role of arachidonic acid
      products of cyclooxygenase in endothelium-dependent relaxation was examined.
      Endothelium removal from rabbit corpora was performed by infusion with 3-[(3
      cholamidopropyl)-dimethylammonio]-1-propane sulfonate and was confirmed by
      transmission electron microscopy. Strips of human and rabbit corporal tissues
      were studied in the organ chambers for isometric tension measurement. The
      accumulation of cyclic guanosine monophosphate (cGMP) and the release of
      eicosanoids from corporal tissue was measured by radioimmunoassay and correlated
      to smooth muscle relaxation. Our study showed that relaxation of corpus
      cavernosum tissue to acetylcholine, bradykinin and substance P was endothelium
      dependent; potentiated by indomethacin; and inhibited by NG-monomethyl-L
      arginine, methylene blue or LY83583. Relaxation to papaverine and sodium
      nitroprusside was endothelium-independent, and unaffected by NG-monomethyl-L
      arginine. Relaxation to vasoactive intestinal polypeptide was partially
      endothelium-dependent; potentiated by indomethacin; attenuated by NG-monomethyl-L
      arginine or methylene blue. The tissue level of cGMP was enhanced by
      acetylcholine and nitric oxide. Methylene blue inhibited both basal and drug
      stimulated levels of cGMP. The release of eicosanoids was enhanced by
      acetylcholine and blocked by indomethacin. In conclusion, nitric oxide or a
      closely related substance accounts for the activity of endothelium-derived
      relaxing factor in the corporal tissue. Inhibition of the release of eicosanoids
      potentiates the relaxing effect of nitric oxide. Nitric oxide increases tissue
      cGMP which appears to modulate corporal smooth muscle relaxation.

PMID- 1370332
TI  - Long-term followup of 150 patients with testicular cancer treated at a single
      institution.
AB  - Between 1977 and 1988, 150 patients with disseminated primary testicular germ
      cell tumors were treated with cisplatin, vinblastine and bleomycin. Of the 150
      patients 90 (60%) achieved a complete response to chemotherapy. An additional 33
      patients achieved a complete response after removal of residual masses following
      chemotherapy. Thus, 123 of 150 patients (82%) achieved a disease-free status
      following chemotherapy with or without an operation. After a median followup of
      49 months the estimated long-term probability of remaining without failure and of
      surviving is 77%. With this data base a multivariate analysis of prognostic
      factors determined the Indiana University staging system to be highly predictive.
      Other staging systems proved to be less useful. The subset of patients with
      minimal and moderate disease by Indiana staging containing mature teratoma in the
      orchiectomy specimen has a particularly excellent prognosis (99% actuarial
      survival) with chemotherapy.

PMID- 1370333
TI  - Interferons: potential problems.

PMID- 1370334
TI  - Carbon monoxide poisoning in children riding in the back of pickup trucks.
AB  - OBJECTIVE - To describe the case characteristics of a series of children poisoned
      with carbon monoxide while traveling in the back of pickup trucks. DESIGN -
      Pediatric cases referred for treatment of carbon monoxide poisoning with
      hyperbaric oxygen between 1986 and 1991 were reviewed. Those cases that occurred
      during travel in the back of pickup trucks were selected. Clinical follow-up by
      telephone interview ranged from 2 to 55 months. SETTING - A private, urban,
      tertiary care center in Seattle, Wash. PATIENTS - Twenty children ranging from 4
      to 16 years of age. INTERVENTION - All patients were treated with hyperbaric
      oxygen. MAIN OUTCOME MEASURES - Characteristics of the poisoning incident and
      clinical patient outcome. RESULTS - Of 68 pediatric patients treated for
      accidental carbon monoxide poisoning, 20 cases occurred as children rode in the
      back of pickup trucks. In 17 of these, the children were riding under a rigid
      closed canopy on the rear of the truck, while three episodes occurred as children
      rode beneath a tarpaulin. Average carboxyhemoglobin level on emergency department
      presentation was 18.2% +/- 2.4% (mean +/- SEM; range, 1.6% to 37.0%). Loss of
      consciousness occurred in 15 of the 20 children. One child died of cerebral
      edema, one had permanent neurologic deficits, and 18 had no recognizable sequelae
      related to the episode. In all cases, the truck exhaust system had a previously
      known leak or a tail pipe that exited at the rear rather than at the side of the
      pickup truck. CONCLUSIONS - Carbon monoxide poisoning is a significant hazard for
      children who ride in the back of pickup trucks. If possible, this practice should
      be avoided.

PMID- 1370335
TI  - Enhancement of HIV-1 infection by the capsular polysaccharide of Cryptococcus
      neoformans.
AB  - Patients with AIDS who become infected with Cryptococcus neoformans have a poor
      prognosis. We speculated that the presence of cryptococcal capsular
      polysaccharide may enhance HIV-1 infection. In an in-vitro study, the presence of
      cryptococcal polysaccharide significantly increased (p less than 0.05) production
      of p24 antigen after infection of H9 cells with HIV-1-infected H9 cells. We also
      found similar results when lymphocytes from an HIV-1-infected patient were co
      cultured with mononuclear cells from an uninfected individual. Our findings
      suggest a new pathogenic role for the capsular polysaccharide--namely, the
      capacity to enhance HIV-1 infectivity.

PMID- 1370336
TI  - Epidermolysis bullosa simplex: a disorder of keratin.

PMID- 1370338
TI  - Clinical practice of radiotherapy.

PMID- 1370337
TI  - Genotype and secretory response in cystic fibrosis.

PMID- 1370339
TI  - Trichuris infection and mental development in children.

PMID- 1370340
TI  - Interaction of thyrotropin and thyroid-stimulating antibodies with recombinant
      extracellular region of human TSH receptor.

PMID- 1370341
TI  - Expression of the Evi-1 zinc finger gene in 32Dc13 myeloid cells blocks
      granulocytic differentiation in response to granulocyte colony-stimulating
      factor.
AB  - Expression of the Evi-1 gene is frequently activated in murine myeloid leukemias
      by retroviral insertions immediately 5' or 90 kb 5' of the gene. The Evi-1 gene
      product is a nuclear, DNA-binding zinc finger protein of 145 kDa. On the basis of
      the properties of the myeloid cell lines in which the Evi-1 gene is activated, it
      has been hypothesized that its expression blocks normal differentiation. To
      explore this proposed role, we have constructed a retrovirus vector containing
      the gene and examined its effects on an interleukin-3-dependent myeloid cell line
      that differentiates in response to granulocyte colony-stimulating factor (G-CSF).
      Expression of the Evi-1 gene in these cells did not alter the normal growth
      factor requirements of the cells. However, expression of the Evi-1 gene blocked
      the ability of the cells to express myeloperoxidase and to terminally
      differentiate to granulocytes in response to G-CSF. This effect was not due to
      altered expression of the G-CSF receptor or to changes in the initial responses
      of the cells to G-CSF. These results support the hypothesis that the
      inappropriate expression of the Evi-1 gene in myeloid cells interferes with the
      ability of the cells to terminally differentiate.

PMID- 1370342
TI  - An intergenic G-rich region in Leishmania tarentolae kinetoplast maxicircle DNA
      is a pan-edited cryptogene encoding ribosomal protein S12.
AB  - Six short G-rich intergenic regions in the maxicircle of Leishmania tarentolae
      are conserved in location and polarity in two other kinetoplastid species. We
      show here that G-rich region 6 (G6) represents a pan-edited cryptogene which
      contains at least two domains edited independently in a 3'-to-5' manner connected
      by short unedited regions. In the completely edited RNA, 117 uridines are added
      at 49 sites and 32 uridines are deleted at 13 sites, creating a translated 85
      amino-acid polypeptide. Similar polypeptides are probably encoded by pan-edited
      G6 transcripts in two other species. The G6 polypeptide has significant sequence
      similarity to the family of S12 ribosomal proteins. A minicircle-encoded gRNA
      overlaps 12 editing sites in G6 mRNA, and chimeric gRNA/mRNA molecules were shown
      to exist, in agreement with the transesterification model for editing.

PMID- 1370344
TI  - Rapid-time-course miniature and evoked excitatory currents at cerebellar synapses
      in situ.
AB  - Neurotransmission from mossy fibre terminals onto cerebellar granule cells is
      almost certainly mediated by L-glutamate. By taking advantage of the small soma
      size, limited number of processes and short dendrite length of granule cells, we
      have obtained high-resolution recordings of spontaneous miniature excitatory
      postsynaptic currents (m.e.p.s.cs) and evoked currents in thin cerebellar slices.
      Miniature currents have a similar time-course and pharmacology to evoked currents
      and consist of an exceptionally fast non-NMDA (N-methyl-D-aspartate) component
      (measured rise-time, 200 microseconds; estimated pre-filtered rise-time less than
      100 microseconds; decay time constant, tau = 1.0 ms), followed by 50 pS NMDA
      channel openings that are directly resolvable. We could find no evidence for the
      recent proposal that miniature currents in granule cells are mediated solely by
      NMDA channels with a novel time course. The non-NMDA receptor component of
      m.e.p.s.cs has a skewed amplitude distribution, which suggests potential
      complications for quantal analysis. The difference in time course between the
      m.e.p.s.cs reported here and other synaptic currents in the brain could reflect
      differences in synaptic function or electrotonic filtering; the relative
      contribution of these possibilities has yet to be established.

PMID- 1370345
TI  - Three-dimensional heteronuclear NMR studies of RNA.
AB  - Multidimensional heteronuclear NMR has revolutionized solution structure
      determinations of proteins. But this technique has not been applied to nucleic
      acids because of difficulties in the synthesis of isotopically (13C and/or 15N)
      labelled molecules. Here we report the application of three-dimensional
      heteronuclear NMR to the study of a uniformly 13C/15N or 15N-labelled RNA duplex
      of defined sequence. These experiments simplify resonance assignment and the
      analysis of proton-proton nuclear Overhauser effects (and therefore distance
      information) in the molecule. Our results show that it is now possible to
      determine the structures of larger and more complex RNAs using multidimensional
      heteronuclear NMR.

PMID- 1370343
TI  - Atomic structure of single-stranded DNA bacteriophage phi X174 and its functional
      implications.
AB  - The mechanism of DNA ejection, viral assembly and evolution are related to the
      structure of bacteriophage phi X174. The F protein forms a T = 1 capsid whose
      major folding motif is the eight-stranded antiparallel beta barrel found in many
      other icosahedral viruses. Groups of 5 G proteins form 12 dominating spikes that
      enclose a hydrophilic channel containing some diffuse electron density. Each G
      protein is a tight beta barrel with its strands running radially outwards and
      with a topology similar to that of the F protein. The 12 'pilot' H proteins per
      virion may be partially located in the putative ion channel. The small, basic J
      protein is associated with the DNA and is situated in an interior cleft of the F
      protein. Tentatively, there are three regions of partially ordered DNA structure,

PMID- 1370346
TI  - Tyrosine phosphorylation is required for ligand-induced internalization of the
      antigen receptor on B lymphocytes.
AB  - The membrane immunoglobulin (mIg) receptor for antigen mediates signal
      transduction in B lymphocytes. Multivalent ligand induces several early
      activation events including an increase in intracellular calcium concentration,
      hydrolysis of phosphatidylinositol, and activation of protein kinase C. Most
      recently, it has been demonstrated that anti-immunoglobulin antibodies induce the
      rapid accumulation of tyrosine phosphorylated proteins and anti-phosphotyrosine
      immune complex-associated kinase activity, both of which require receptor
      crosslinking. Multivalent ligand binding of mIg also results in its association
      with detergent-insoluble cytoskeletal components and with a slight lag period, in
      a characteristic pattern of patching, followed by polar capping and finally
      internalization of the receptors. In this report, we demonstrate that two
      specific inhibitors of tyrosine phosphorylation, a tyrphostin and genistein,
      retard the modulation of mIg on the cell surface and inhibit ligand-induced
      receptor internalization. We conclude that in B cells, tyrosine phosphorylation
      occurs as the result of crosslinking mIg and is required for subsequent
      internalization of mIg-ligand complexes. This suggests that tyrosine
      phosphorylation may be important for B cells to function as specific antigen
      presenting cells.

PMID- 1370347
TI  - Synthetic copolymer 1 inhibits human T-cell lines specific for myelin basic
      protein.
AB  - Copolymer 1 (Cop 1) is a synthetic basic random copolymer of amino acids that has
      been shown to be effective in suppression of experimental allergic
      encephalomyelitis and has been proposed as a candidate drug for multiple
      sclerosis. Cop 1 is immunologically cross reactive with myelin basic protein (BP)
      and was shown to inhibit murine BP-specific T-cell lines of various H-2
      restrictions. In the present study these findings were extended to include human
      T-cell lines. Cop 1 competitively inhibited the proliferative responses and
      interleukin 2 secretion of six BP-specific T-cell lines and 13 clones with
      several DR restrictions and epitope specificities. Conversely, BP inhibited-
      albeit to a lesser extent--the response of all the Cop 1-specific T-cell lines
      and clones, irrespective of their DR restrictions. Another random copolymer of
      tyrosine, glutamic acid, and alanine, denoted TGA, had no effect on these lines.
      Neither Cop 1 nor BP inhibited the response of lines and clones specific for
      purified protein derivative. Cop 1 and BP exerted their cross-inhibitory effects
      only in the presence of antigen-presenting cells. These results suggest that Cop
      1 can compete with BP for the binding to human major histocompatibility complex
      molecules. In view of recent studies implicating BP reactivity in multiple
      sclerosis, these findings suggest a possible mechanism for the beneficial effect
      of Cop 1 in this disease.

PMID- 1370348
TI  - Infectious enveloped RNA virus antigenic chimeras.
AB  - Random insertion mutagenesis has been used to construct infectious Sindbis virus
      structural protein chimeras containing a neutralization epitope from a
      heterologous virus, Rift Valley fever virus. Insertion sites, permissive for
      recovery of chimeric viruses with growth properties similar to the parental
      virus, were found in the virion E2 glycoprotein and the secreted E3 glycoprotein.
      For the E2 chimeras, the epitope was expressed on the virion surface and
      stimulated a partially protective immune response to Rift Valley fever virus
      infection in vivo. Besides providing a possible approach for developing live
      attenuated vaccine viruses, insertion of peptide ligands into virion surface
      proteins may ultimately allow targeting of virus infection to specific cell
      types.

PMID- 1370349
TI  - Murine B7 antigen provides an efficient costimulatory signal for activation of
      murine T lymphocytes via the T-cell receptor/CD3 complex.
AB  - We demonstrate that the murine B7 (mB7) protein is a potent costimulatory
      molecule for the activation of resting murine CD4+ T cells through the T-cell
      receptor (TCR)/CD3 complex. Stable mB7-transfected Chinese hamster ovary cells,
      but not vector-transfected controls, synergize with anti-CD3 monoclonal antibody
      and Con A-induced T-cell activation, resulting ultimately in proliferation. mB7
      exerted its effect by inducing production of interleukin 2 and expression of the
      interleukin 2 receptor. Thus, mB7 costimulates T-cell activation through the
      TCR/CD3 complex by positively modulating the normal pathway of T-cell expansion.
      In contrast to the pronounced effect of mB7 on the activation of T cells through
      the TCR/CD3 complex, the mB7-transfected CHO cell line costimulated T-cell
      activation via the glycosylphosphatidylinositol-anchored proteins Thy-1 and Ly
      6A.2 only inefficiently. Finally, the combination of a calcium ionophore and mB7
      is not sufficient to cause T-cell proliferation, while the combination of a
      calcium ionophore and phorbol 12-myristate 13-acetate (PMA) stimulates T cells
      efficiently. The signals that mB7 and PMA provide for murine T lymphocyte
      activation are therefore not interchangeable, although both costimulate
      activation through the TCR/CD3 complex.

PMID- 1370351
TI  - Single amino acid change in the helicase domain of the putative RNA replicase of
      turnip crinkle virus alters symptom intensification by virulent satellites.
AB  - The virulent satellite [satellite C (sat C)] of turnip crinkle virus (TCV) is a
      small pathogenic RNA that intensifies symptoms in TCV-infected turnip plants
      (Brassica campestris). The virulence of sat C is determined by properties of the
      satellite itself and is influenced by the helper virus. Symptoms produced in
      infections with sat C differ in severity depending on the helper virus. The TCV
      JI helper virus produces more severe symptoms than the TCV-B helper virus when
      inoculated with sat C. To find determinants in the TCV helper virus genome that
      affect satellite virulence, the TCV-JI genome was cloned and the sequence
      compared to the TCV-B genome. The genomes were found to differ by only five base
      changes, and only one of the base changes, at nucleotide position 1025, produced
      an amino acid change, an aspartic acid----glycine in the putative viral
      replicase. A chimeric TCV genome (TCV-B/JI) containing four of the five base
      changes (including the base change at position 1025) and a mutant TCV-B genome
      (TCV-B1025G) containing a single base substitution at position 1025 converted the
      TCV-B genome into a form that produces severe symptoms with sat C. The base
      change a position 1025 is located in the helicase of the putative viral
      replicase, and symptom intensification appears to result from differences in the
      rate of replication of the satellite supported by the two helper viruses.

PMID- 1370350
TI  - Sulfhydryl oxidation down-regulates T-cell signaling and inhibits tyrosine
      phosphorylation of phospholipase C gamma 1.
AB  - Early events in both T-cell receptor (CD3)- and CD4-induced signal transduction
      pathways include tyrosine phosphorylation of protein substrates, the generation
      of phosphatidylinositol-phosphate breakdown products, and the mobilization of
      intracellular Ca2+. Oxidative stress in T cells mediated by sulfhydryl-reactive
      nonpolar maleimides was shown previously to down-regulate both receptor-mediated
      Ca2+ mobilization and interleukin 2 production. Here we show that N
      ethylmaleimide suppresses both CD3- and CD4-induced Ca2+ responses in human T
      cells correlating with a reduction in the level of phospholipase C gamma 1 (PLC
      gamma 1) tyrosine phosphorylation. The inhibition of tyrosine phosphorylation of
      PLC gamma 1 and additional protein substrates was observed at concentrations of N
      ethylmaleimide above 20 microM, whereas lower concentrations of oxidant appeared
      to increase tyrosine kinase activity following cell stimulation. Sulfhydryl
      oxidation did not directly affect the catalytic activity of PLC gamma 1, since
      immunopurified enzyme from N-ethylmaleimide-treated T cells was fully active.
      Although N-ethylmaleimide treatment of T cells did not cause a direct effect on
      total pp56lck kinase activity measured in vitro, the interaction between CD4 and
      pp56lck was oxidation-sensitive in vivo. However, CD3-induced signaling was
      inhibited at N-ethylmaleimide concentrations lower than that required for
      CD4/pp56lck dissociation, suggesting that CD3-associated tyrosine kinase activity
      involves acutely sensitive regulatory thiols. In addition to chemically induced
      sulfhydryl oxidation, naturally regulated cellular redox states appear to dictate
      the potential for T-cell responsiveness, since degranulating human peripheral
      blood neutrophils inhibited CD3-induced Ca2+ mobilization in T lymphocytes. These
      data indicate that signal transduction in T cells involves the activation of PLC
      gamma 1 by tyrosine phosphorylation through an oxidation-sensitive intermediate
      between surface receptors and tyrosine kinases, perhaps including the interaction
      between CD4 and pp56lck.

PMID- 1370352
TI  - Molecular basis of recognition by the glycoprotein hormone-specific N
      acetylgalactosamine-transferase.
AB  - Lutropin (LH) bears asparagine-linked oligosaccharides terminating with the
      unique sequence SO4-4GalNAc beta 1-4GlcNAc beta 1-2Man alpha, whereas follitropin
      (FSH) bears oligosaccharides terminating predominantly with the sequence Sia
      alpha-Gal beta 1-4GlcNAc beta 1-2Man alpha, where Sia is sialic acid. We
      previously identified a glycoprotein-hormone-specific N-acetylgalactosamine
      transferase (GalNAc-transferase) that recognizes a peptide-recognition marker(s)
      present on the common glycoprotein hormone alpha subunit and beta subunits of
      human chorionic gonadotropin and LH but not on the beta subunit of FSH. We have
      now identified an amino acid sequence motif, Pro-Leu-Arg, that is essential for
      recognition by the GalNAc-transferase. This tripeptide sequence is found 6-9
      residues on the amino-terminal side of a glycosylated asparagine on the alpha
      subunit and beta subunits of LH and human chorionic gonadotropin but is not
      present on the beta subunit of FSH. The presence of this motif accounts for the
      differences in LH and FSH oligosaccharide structures. Additional proteins
      containing this recognition motif have been identified and were determined to
      bear sulfated oligosaccharides with the same structures as those on the
      glycoprotein hormones, indicating that these structures are not restricted to the
      glycoprotein hormones.

PMID- 1370353
TI  - CFTR protein expression in primary and cultured epithelia.
AB  - The gene responsible for the lethal disorder cystic fibrosis encodes a 1480-amino
      acid glycoprotein, CFTR. Using polyclonal antibodies directed against separate
      phosphorylation sites in the pre-nucleotide-binding fold (exon 9) and the R
      domain (exon 13), we have identified a 165-kDa protein in Xenopus laevis oocytes
      injected with recombinant CFTR cRNA transcribed from the full-length CFTR plasmid
      pBQ4.7. A protein of the same mobility was also detected with Western blotting
      techniques in whole cell extracts of cells that express CFTR mRNA (T84, FHTE, HT
      29), including biopsied human nasal and bronchial tissue. Immunodetectable 165
      kDa protein was concentrated in the apical membrane fraction of ileal villus
      tissue. We also report that the 165-kDa protein levels can be modulated
      pharmacologically, and these levels are appropriately correlated with second
      messenger-regulated Cl- efflux. Thus, native or recombinant CFTR can be
      recognized by these anti-CFTR peptide polyclonal antibodies.

PMID- 1370354
TI  - Interferons and interleukin 6 suppress phosphorylation of the retinoblastoma
      protein in growth-sensitive hematopoietic cells.
AB  - One approach to identify postreceptor molecular events that transduce the
      negative-growth signals of inhibitory cytokines is to analyze the cytokine
      induced modifications in the expression of cell-cycle-controlling genes. Here we
      report that suppression of phosphorylation of the retinoblastoma gene product
      (pRb) is a receptor-generated event triggered by interferons and interleukin 6
      (IL-6) in hematopoietic cell lines. The conversion of pRb to the
      underphosphorylated forms occurs concomitantly with the decline in c-myc protein
      expression and both events precede the G0/G1-phase arrest induced by the
      cytokines. Loss of IL-6-induced c-myc responses in cells that have been stably
      transfected with constitutive versions of the c-myc gene abrogates the typical
      G0/G1-phase arrest but does not prevent the specific dephosphorylation of pRb.
      Conversely, depletion of protein kinase C from cells interferes with part of the
      interferon-induced suppression of pRb phosphorylation and relieves the G0/G1
      phase cell-cycle block without affecting the extent of c-myc inhibition. None of
      the cytokines, including transforming growth factor beta, reduce the
      phosphorylation of pRb in S-phase-blocked cells. In contrast, the other IL-6
      induced molecular responses, including the decline in c-myc mRNA levels, are not
      phase-specific and develop normally in S-phase-blocked cells that are depleted of
      the underphosphorylated functional forms of pRb. These and the suppression of pRb
      phosphorylation, which occur independently of each other, and suggest that the
      development of the interferon- or IL-6-induced G0/G1-specific arrest requires at
      least these two receptor-generated events.

PMID- 1370355
TI  - Tolerance to a self-protein involves its immunodominant but does not involve its
      subdominant determinants.
AB  - We have produced transgenic mice expression hen egg-white lysozyme (HEL) under
      the control of a ubiquitous promoter, so that in transgenic animals, HEL is
      presumably present in the serum and thymus throughout the period of establishment
      of the T-cell repertoire. We show that HEL transgenic H-2d mice with HEL blood
      levels greater than 10 ng/ml are tolerant to HEL as well as to the immunodominant
      peptide 108-116. Thus, their T lymphocytes do not proliferate in response to the
      immunodominant peptide 108-116 after in vivo immunization with HEL or peptide 108
      116. In contrast, in transgenic mice tolerant to HEL, the state of tolerance to
      subdominant peptides 1-18 and 74-96 appears variable and highly depended on HEL
      blood levels. Complete unresponsiveness is seen when HEL serum levels are high,
      and this unresponsiveness is reached at a lower HEL concentration for peptide 1
      18 than for peptide 74-96. Thus, a hierarchy exists among the three peptides (108
      116 much greater than 1-18 greater than 74-96) for induction of a response to HEL
      and for HEL tolerance induction in T cells specific for these peptides.
      Persistence in the periphery of autoreactive T cells recognizing subdominant
      peptides of self-proteins, as shown in this transgenic model, indicates that self
      tolerance is limited to a subset of dominant self-peptides and suggests a role
      for T lymphocytes specific for subdominant determinants in autoimmunity.

PMID- 1370356
TI  - Suppressor T cells generated by oral tolerization to myelin basic protein
      suppress both in vitro and in vivo immune responses by the release of
      transforming growth factor beta after antigen-specific triggering.
AB  - Oral administration of myelin basic protein (MBP) is an effective way of
      suppressing experimental autoimmune encephalomyelitis (EAE). We have previously
      shown that such suppression is mediated by CD8+ T cells, which adoptively
      transfer protection and suppress immune responses in vitro. In the present study
      we have found that modulator cells from animals orally tolerized to MBP produce a
      suppressor factor upon stimulation with MBP in vitro that is specifically
      inhibited by anti-transforming growth factor beta (TGF-beta) neutralizing
      antibodies. No effect was observed with antibodies to gamma interferon, tumor
      necrosis factor alpha/beta, or indomethacin. In addition, the active form of the
      type 1 isoform of TGF-beta 1 (TGF-beta 1) can be directly demonstrated in the
      supernatants of cells from animals orally tolerized to MBP or ovalbumin after
      antigen stimulation in vitro. Antiserum specific for TGF-beta 1 administered in
      vivo abrogated the protective effect of oral tolerization to MBP in EAE.
      Furthermore, injection of anti-TGF-beta 1 serum to nontolerized EAE animals
      resulted in an increase in severity and duration of disease. These results
      suggest that immunomodulation of EAE induced by oral tolerization to MBP and
      natural recovery mechanisms use a common immunoregulatory pathway that is
      dependent on TGF-beta 1. Implications of such an association are of therapeutic
      relevance to human autoimmune diseases and may help to explain one of the
      mechanisms involved in the mediation of active suppression by T cells.

PMID- 1370357
TI  - Identification of a macrophage-binding determinant on lipophosphoglycan from
      Leishmania major promastigotes.
AB  - Leishmania are obligatory intracellular parasites in mammalian macrophages that
      gain entry by receptor-mediated phagocytosis. Their major cell surface
      glycoconjugate, lipophosphoglycan (LPG), has been implicated in this process. A
      monoclonal antibody specific for Leishmania major LPG (WIC 79.3), which has been
      shown to block promastigote attachment to macrophages, was used to identify a
      macrophage-binding determinant of LPG. WIC 79.3 bound exclusively to the
      phosphorylated repeats of LPG and not to the saccharide core or lipid anchor.
      Furthermore, the epitope recognized by WIC 79.3 mapped to the phosphorylated
      oligosaccharide P5b, PO4-6[Gal(beta 1-3)Gal(beta 1-3)Gal(beta 1-3)]Gal(beta 1
      4)Man(alpha 1-, which is unique to the LPG of promastigotes of L.major.
      Phosphorylated oligosaccharides P3, PO4-6[Gal(beta 1-3)[Gal(beta 1-4) Man(alpha 1
      , and P4b, PO4-6[Gal(beta 1-3)Gal(beta 1-3)] Gal(beta 1-4)Man(alpha 1-, were also
      recognized by WIC 79.3 but with considerably lower (approximately 100-fold)
      affinities. The phosphorylated oligosaccharide P5b inhibited attachment of
      promastigotes of L. major to the macrophage cell line J774 to the same degree as
      phosphoglycan (derived from LPG) and Fab fragments of WIC 79.3, suggesting that
      P5b is a site of L. major LPG that is recognized by macrophage receptor(s) and is
      an important determinant in the attachment of promastigotes to host macrophages
      and initiation of infection.

PMID- 1370359
TI  - Characteristics of anal canal motility after ileoanal anastomosis.
AB  - This study attempted to determine the mechanism of anal canal motility after
      ileoanal anastomosis with the use of alpha-, beta- and muscarinic receptor
      agents. Forty-five patients, 19 +/- 2 months after operation (mean plus or minus
      S.E.M.) and 48 control volunteers were studied. Anal manometry indicated no
      difference in maximum resting pressure and squeeze pressure between the patients
      and the normal controls. Greater amplitude and less frequent anal canal slow
      waves were a particular characteristic during the postoperative period.
      Phentolamine (alpha-blocker) exhibited a stimulatory effect on anal resting tone
      in the normal rectum, while propranolol (beta-blocker) and atropine (muscarinic
      blocker) had no effect. However, alpha-, beta- and muscarinic receptors all had
      stimulatory effects on postoperative anal tone. The muscarinic receptor had
      dominant effects on the reduction in anal canal slow wave frequency after
      ileoanal anastomosis. Our results indicated that neorectum after ileoanal
      anastomosis had hybrid characteristics of both rectum and ileum. Through analysis
      of receptor-related motor function, we may be able to improve our understanding
      of dyscontinence after ileoanal anastomosis.

PMID- 1370358
TI  - Monoclonal IgM rheumatoid factors bind IgG at a discontinuous epitope comprised
      of amino acid loops from heavy-chain constant-region domains 2 and 3.
AB  - A combination of site-directed mutagenesis and exon exchange has been used to
      further define the structure on IgG recognized by monoclonal IgM rheumatoid
      factors (RFs) from patients with Waldenstrom macroglobulinemia. Most of these RFs
      bound IgG1, -2, and -4 but not IgG3. For these RFs, His-435 is a critical residue
      for binding and replacing it with arginine, the residue present in IgG3, destroys
      or reduces RF binding. However, additional polymorphic sequences in both the
      heavy-chain constant-region domains (CH) 2 and 3 are important for RF binding.
      Among the important residues in CH2 are amino acids 252-254 and 309-311, which
      are conserved among IgG isotypes and comprise two loops of amino acids on the
      surface of the domain. Therefore, at least three regions, two from CH2 and one
      from CH3, contribute significantly to the epitope recognized by the RFs. Although
      this epitope contains many of the same residues as the staphylococcal protein A
      binding site on IgG, the binding specificities of staphylococcal protein A and
      monoclonal RFs are not identical. Sera from patients with rheumatoid arthritis
      contain antibodies directed not only at this epitope but also at other sites on
      IgG.

PMID- 1370360
TI  - Cadmium's action on NRK-49F cells to produce responses induced also by TGF beta
      is not due to cadmium induced TGF beta production or activation.
AB  - Transforming growth factor beta (TGF beta) is a multifunctional regulator of cell
      growth that has either a stimulatory or inhibitory effect on cell proliferation,
      depending on TGF beta concentration and on cell type, history and culture
      conditions. Cadmium mimics some of the effects of TGF beta in cultured cells. In
      this study the effects of Cd2+ and TGF beta on EGF-induced DNA synthesis in a
      clonal subpopulation (N1) of NRK-49F cells were compared. It was found that TGF
      beta 1 and cadmium both inhibit EGF-induced DNA synthesis and cell proliferation
      in a dose-dependent fashion, but that neither inhibits EGF-induced myc oncogene
      accumulation. TGF beta 1 and cadmium added at the same time as EGF or several
      hours after EGF addition showed similar inhibitory effects on EGF-induced [3H]Tdr
      incorporation, indicating that the inhibitory effect of TGF beta 1 and cadmium on
      EGF-induced DNA synthesis does not involve early G1 events. Rather, they occur in
      late G1, at the G1/S boundary or during S phase. Because of the similarities in
      nature and timing of the Cd2+ and TGF beta responses, the possibility that Cd2+
      acts through stimulation of TGF beta production and/or activation was explored.
      It is shown in this paper however that TGF beta neutralizing antibody blocks the
      effects of TGF beta 1, but not the cadmium effects, on EGF-induced DNA synthesis,
      suggesting that cadmium is not functioning through activation or preinduction of
      TGF beta.

PMID- 1370361
TI  - Effect of 2-acetylaminofluorene on intracellular free Ca2+ in isolated rat
      hepatocytes.
AB  - The effect of 2-acetylaminofluorene (2-AAF) on the intracellular free Ca2+
      ([Ca2+]i) and viability of isolated rat hepatocytes has been investigated using
      the fluorescent probes quin 2 and propidium iodide respectively. At the highest
      concentration tested (224 microM), 2-AAF produces an elevation of [Ca2+]i which
      shows a biphasic profile. A small initial increase is observed during the first 5
      min; this is followed by a considerable rise which reaches up to 2.5 times the
      control value at 15 min. These changes in intracellular calcium are not
      accompanied by detectable alterations in cell viability. In order to determine
      the mechanisms by which this effect of 2-AAF takes place, three calcium
      antagonists, namely verapamil, TMB-8 (8-(diethylamino)-octyl-3,4,5
      trimethoxybenzoate) and ruthenium red (RuR), have been used. The results suggest
      that the first phase is dependent upon internal Ca2+ store mobilization, while
      the second phase seems to be related to Ca2+ entry from the extracellular space.
      The data obtained with RuR further indicate that mitochondria may be involved in
      the perturbation of calcium homeostasis caused by 2-AAF. In addition, in the
      experiments involving antagonists, no consistent pattern emerges that suggests a
      close relationship between intracellular Ca2+ levels and cell viability. The
      present study provides further information on the mechanisms by which these well
      known hepatotoxin 2-AAF may interact with liver cells. It also shows that when
      these cells are exposed to a toxin, short-term changes in [Ca2+]i may not be
      accompanied by loss of cell viability, and conversely, that changes in cell
      viability may occur without alterations in [Ca2+]i.

PMID- 1370362
TI  - MR imaging of joints: analytic optimization of GRE techniques at 1.5 T.
AB  - To clarify the choice of imaging parameters for optimal gradient-recalled echo MR
      scanning of joints, we analyzed the behavior of contrast-to-noise and signal-to
      noise ratios for spoiled (i.e., fast low-angle shot [FLASH] or spoiled GRASS) and
      steady-state (i.e., gradient-recalled acquisition in the steady state [GRASS] or
      fast imaging with steady precession) techniques at 1.5 T. The analysis is based
      on tissue characteristics derived from spin-echo measurements of hyaline
      cartilage and synovial fluid signal in the patellofemoral joints of 11
      volunteers. Separate analysis of contrast-to-noise and signal-to-noise ratios for
      multiplanar (long TR) acquisitions shows that these parameters are each improved
      compared with single-slice methods. At TRs greater than 250 msec, there is no
      significant difference in the contrast behavior of FLASH and GRASS. For optimal
      contrast-to-noise ratio (synovial fluid-cartilage), the best multiplanar sequence
      (for TE less than 23 msec) is with a short TE and a large flip angle (e.g.,
      400/9/73 degrees [TR/TE/flip angle]). If a single-scan or three-dimensional
      technique is desired, than a GRASS sequence at minimal TR and TE and intermediate
      flip angle (18/9/32 degrees) is best. For optimal signal-to-noise ratio (for both
      synovial fluid and hyaline cartilage), the best multiplanar sequence uses a short
      TE and an intermediate flip angle (e.g., 400/9/30 degrees). If a short TR, high
      signal-to-noise technique is desired, then GRASS (18/9/13 degrees) is superior to
      FLASH.

PMID- 1370363
TI  - Ventricular dysrhythmias in patients undergoing coronary artery bypass graft
      surgery: incidence, characteristics, and prognostic importance. Study of
      Perioperative Ischemia (SPI) Research Group.
AB  - To determine the incidence and characteristics of ventricular dysrhythmias
      (premature ventricular contractions greater than 30/min, ventricular tachycardia
      greater than or equal to 3 beats, and ventricular fibrillation) and whether a
      relationship exists between ventricular tachycardia and myocardial ischemia in
      patients undergoing coronary artery bypass graft surgery, we continuously
      monitored 50 patients for 10 perioperative days using two-lead
      electrocardiography. Electrocardiographic changes consistent with ischemia were
      defined as a reversible ST depression greater than or equal to 1.0 mm, or ST
      elevation greater than or equal to 2.0 mm from baseline, lasting at least 1
      minute. Ventricular dysrhythmias developed in 10% of patients preoperatively and
      in 16% intraoperatively before bypass surgery. The highest incidence occurred
      postoperatively, with ventricular dysrhythmias developing in 66% of patients (22%
      to 44% of patients on any postoperative day 0 to 7). Premature ventricular
      contractions were greater than 30/hr in 6% of patients preoperatively, in 8%
      intraoperatively before bypass, and in 34% postoperatively (6% to 23% of patients
      on any postoperative day). Twenty-nine patients (58%) developed 76 verified
      episodes of greater than or equal to 3 beats of ventricular tachycardia.
      Ventricular tachycardia occurred in 6% of patients preoperatively (four
      episodes), in 8% of patients intraoperatively prior to bypass (four episodes),
      and 54% of patients postoperatively (5% to 21% on any postoperative day). No
      patient developed ventricular fibrillation. All postoperative ventricular
      tachycardia episodes (after tracheal extubation) were asymptomatic.
      Postoperatively, 48% of patients developed ischemia, compared with 12%
      preoperatively and 10% intraoperatively before bypass surgery. Only 5 of 68 (7%)
      postoperative ventricular tachycardia episodes occurred within 3 hours of an
      ischemia episode.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370364
TI  - Two amino acid substitutions in apolipoprotein B are in complete allelic
      association with the antigen group (x/y) polymorphism: evidence for little
      recombination in the 3' end of the human gene.
AB  - We report the identification of an A-to-G base change, in exon 29 of the
      apolipoprotein B (apo B) gene, that results in the substitution of serine for
      asparagine at residue 4311 of mature apo B100. In a recent publication, Huang et
      al. have reported a C-to-T base change in exon 26 that causes the substitution of
      leucine for proline at residue 2712 of apo B. We have found complete linkage
      disequilibrium between the alleles at both these sites and an immunochemical
      polymorphism of LDL designated antigen group (x/y) (Ag(x/y)) in a sample of 118
      Finnish individuals. This implies that either one of these substitutions--or both
      of them combined--could be the molecular basis of the Ag(x/y) antigenic
      determinants, with the allele encoding serine4311 plus leucine2712 representing
      the Ag(x) epitope, and that encoding asparagine4311 plus proline2712 the Ag(y)
      epitope. In a sample of 90 healthy Swedish individuals the Leu2712/Ser4311 allele
      is associated both with reduced serum levels of LDL-cholesterol and apo B and
      with raised levels of HDL. However, these differences are of smaller effect than
      those associated with the XbaI RFLP of the apo B gene in this sample. We have
      also genotyped 523 individuals from European, Asian, Chinese, and Afro-Caribbean
      populations and have found complete association between the sites encoding
      residues 2712 and 4311 in all of these samples, although there are large allele
      frequency differences between these populations. In addition, there is strong
      linkage disequilibrium with allelic association between the alleles of these
      sites and those of the XbaI RFLP in all the populations examined. Taken together,
      these data suggest that, since the divergence of the major ethnic groups, there
      has been little or no recombination in the 3' end of the human apo B gene.

PMID- 1370366
TI  - [A case of verrucous carcinoma showing a good partial response by C.P.E. (CDDP,
      PEP, etoposide) chemotherapy].
AB  - A 60-year-old woman was admitted to our hospital with a complaint of rough
      feeling on the oral mucosa and diagnosed as verrucous carcinoma with
      histopathological examination. She was treated with CPE chemotherapy, and showed
      a good response and improvement of clinical symptoms. Toxicities were leukopenia,
      alopecia and anorexia. However, these were slight side effects. The patient is
      currently healthy with no recurrence after two years and 3 months. CPE
      chemotherapy is considered to be effective for a patient with verrucous
      carcinoma.

PMID- 1370365
TI  - Association of a nonsense mutation (W1282X), the most common mutation in the
      Ashkenazi Jewish cystic fibrosis patients in Israel, with presentation of severe
      disease.
AB  - Only about 30% of the cystic fibrosis chromosomes in the Israeli cystic fibrosis
      patient populations carry the major CF mutation (delta F508). Since different
      Jewish ethnic groups tended to live as closed isolates until recent times, high
      frequencies of specific mutations are expected among the remainder cystic
      fibrosis chromosomes of these ethnic groups. Genetic factors appear to influence
      the severity of the disease. It is therefore expected that different mutations
      will be associated with either severe or mild phenotype. Direct genomic
      sequencing of exons included in the two nucleotide-binding folds of the putative
      CFTR protein was performed on 119 Israeli cystic fibrosis patients from 97
      families. One sequence alteration which is expected to create a termination at
      residue 1282 (W1282X) was found in 63 chromosomes. Of 95 chromosomes, 57 (60%)
      are of Ashkenazi origin. Together with the delta F508 (23% in this group), G542X,
      N1303K, and 1717-1G----A mutations, the identification of 92% of cystic fibrosis
      chromosomes of Ashkenazi origin becomes possible. Patients homozygous for the
      W1282X mutation (n = 16) and patients heterozygous for the delta F508 and W1282X
      mutations (n = 22) had similarly severe disease, reflected by pancreatic
      insufficiency, high incidence of meconium ileus (37% and 27%, respectively),
      early age at diagnosis, poor nutritional status, and variable pulmonary function.
      In conclusion, the W1282X mutation is the most common cystic fibrosis mutation in
      the Ashkenazi Jewish patient population in Israel. This nonsense mutation is
      associated with presentation of severe disease.

PMID- 1370367
TI  - Antibody-dependent enhancement of hantavirus infection in macrophage cell lines.
AB  - Antibody-dependent enhancement (ADE) of hantavirus infections (strains Hantaan 76
      118 and SR-11) was studied using macrophage-like cell lines (J774.1, P388D1, and
      U937). Significantly higher virus titers (1,000 to 4,000 FFU/ml) were obtained by
      pretreatment of the virus with immune serum as compared to normal serum (less
      than 20 FFU/ml). Monoclonal antibodies (MAbs) to strain Hantaan 76-118 were
      employed to determine the antigenic determinants responsible for the ADE
      activity. ADE of the infection occurred with MAbs to both G1 and G2 envelope
      glycoproteins, but not with MAbs to nucleocapsid protein. Antigenic determinants
      related to haemagglutination or virus neutralization were found to cause ADE of
      the infection.

PMID- 1370368
TI  - Effect of macrophage source and activation on susceptibility in an age-dependent
      model of murine hepatitis caused by a phlebovirus, Punta Toro.
AB  - The Adames strain of a bunyavirus, Punta Toro virus (PTV), is an hepatotrophic
      virus that has been described to produce an age-dependent lethal hepatic necrosis
      in 3-4 week old C57BL/6 mice, but 8 week old mice survive with minimal necrosis.
      The course of PTV infection in vitro in macrophages derived from these mice
      served as a model to study the pathogenesis of phlebovirus infection. Peripheral
      blood monocytes, resident or elicited peritoneal macrophages, and Kupffer cell
      liver macrophages, as well as hepatocytes, were able to support replication of
      PTV in vitro to a variable extent. Kupffer cells were the only population of
      macrophages, however, that expressed an age-related ability to affect viral
      infection and replication in vitro, suggesting that liver macrophages may have a
      unique modulatory effect on the occurrence and severity of PTV-induced hepatitis
      in mice. Whereas PTV showed minimal replication in resident peritoneal
      macrophages, the virus could replicate effectively in peritoneal macrophages
      elicited by thioglycolate. Activation of peritoneal macrophages with endotoxin
      resulted in a significant inhibition of intrinsic PTV replication (p less than
      0.001), and a modest extrinsic inhibitory effect on PTV replication in cocultured
      hepatocytes. Both effects persisted in the presence of anti-interferon. These
      results indicate that the source and state of activation of macrophage/monocyte
      populations can influence the course of infection in vitro by the phlebovirus,
      Punta Toro, and can modulate infection in cocultured target cells.

PMID- 1370369
TI  - Molecular cloning and characterization of the fusaric acid-resistance gene from
      Pseudomonas cepacia.
AB  - Fusaric acid-resistance genes (fus) were isolated from Pseudomonas cepacia. The
      nucleotides of the 5437 base pairs containing the fus genes were sequenced.

PMID- 1370370
TI  - Calcium modulation and high calcium permeability of neuronal nicotinic
      acetylcholine receptors.
AB  - Two properties were found to distinguish neuronal from muscle nicotinic
      acetylcholine receptors (nAChRs). First, neuronal nAChRs have a greater Ca2+
      permeability. The high Ca2+ flux through neuronal nAChRs activates a Ca(2+)
      dependent Cl- conductance, and the Ca2+ to Cs+ permeability ratio (PCa/PCs) is 7
      times greater for neuronal than for muscle nAChRs. A second difference between
      the receptor types is that neuronal nAChRs are potently modulated by
      physiological levels of external Ca2+. Neuronal nAChR currents are enhanced by
      external Ca2+ in a dose-dependent manner. The results indicate that changes in
      extracellular Ca2+ modulate neuronal nAChRs and may modulate cholinergic synapses
      in the CNS. Also, activation of neuronal nAChRs produces a significant influx of
      Ca2+ that could be an important intracellular signal.

PMID- 1370371
TI  - Slow voltage-dependent changes in channel open-state probability underlie
      hysteresis of NMDA responses in Mg(2+)-free solutions.
AB  - Many single-channel studies rely on the assumption that the channels are
      functioning under steady-state conditions. In examining the basis for nonlinear
      whole-cell current-voltage curves in Mg(2+)-free solutions we discovered that N
      methyl-D-aspartate (NMDA) channels in excised patches reversibly shifted their
      open-state probability (Po) in a voltage-dependent way, exhibiting approximately
      3- to 4-fold greater Po at positive potentials than at rest. Changes in Po were
      mainly attributable to shifts in frequency of channel opening. Po changed
      remarkably slowly (2-15 min), explaining the hysteresis of whole-cell current
      voltage curves obtained in nonequilibrium conditions. The slow increase in Po
      provides a mechanism by which NMDA channels can substantially increase Ca2+
      influx in cells depolarized for prolonged periods of time and may play a role in
      excitotoxicity.

PMID- 1370372
TI  - Divalent ion permeability of AMPA receptor channels is dominated by the edited
      form of a single subunit.
AB  - Functionally diverse GluR channels of the AMPA subtype are generated by the
      assembly of GluR-A, -B, -C, and -D subunits into homo- and heteromeric channels.
      The GluR-B subunit is dominant in determining functional properties of
      heteromeric AMPA receptors. This subunit exists in developmentally distinct
      edited and unedited forms, GluR-B(R) and GluR-B(Q), which differ in a single
      amino acid in transmembrane segment TM2 (Q/R site). Homomeric GluR-B(R) channels
      expressed in 293 cells display a low divalent permeability, whereas homomeric
      GluR-B(Q) and GluR-D channels exhibit a high divalent permeability. Mutational
      analysis revealed that both the positive charge and the size of the amino acid
      side chain located at the Q/R site control the divalent permeability of homomeric
      channels. Coexpression of Q/R site arginine- and glutamine-containing subunits
      generates cells with varying divalent permeabilities depending on the amounts of
      expression vectors used for cell transfection. Intermediate divalent
      permeabilities were traced to the presence of both divalent permeant homomeric
      and impermeant heteromeric channels. It is suggested that the positive charge
      contributed by the arginine of the edited GluR-B(R) subunit determines low
      divalent permeability in heteromeric GluR channels and that changes in GluR-B(R)
      expression regulate the AMPA receptor-dependent divalent permeability of a cell.

PMID- 1370373
TI  - Nitric oxide, a novel neuronal messenger.

PMID- 1370374
TI  - Molecular cloning and single-channel properties of the cyclic nucleotide-gated
      channel from catfish olfactory neurons.
AB  - We have cloned a functional cDNA encoding the cyclic nucleotide-gated channel
      selectively expressed in catfish olfactory sensory neurons. The cyclic nucleotide
      gated channels share sequence and structural features with the family of voltage
      gated ion channels. This homology is most evident in transmembrane region S4, the
      putative voltage sensor domain, and the H5 domain, thought to form the channel
      pore. We have characterized the single-channel properties of the cloned catfish
      channel and compared these properties with the channel in native catfish
      olfactory sensory neurons. The channel is activated equally well by cAMP and
      cGMP, shows only a slight voltage dependence of gating, and exhibits a pH- and
      voltage-dependent subconductance state similar to that observed for the voltage
      gated L-type calcium channel.

PMID- 1370375
TI  - Sexual differentiation and regulation of cytochrome P-450 CYP2C7.
AB  - The multigene family of proteins known as the cytochrome P-450-dependent
      monooxygenases play a central role in the metabolism of hormones and foreign
      compounds. As part of our studies into the function and regulation of these
      proteins we have isolated a little studied constitutively expressed isozyme
      CYP2C7 and have investigated its substrate specificity and mode of regulation.
      Interestingly the haem of this enzyme in its isolated form is almost 100% in the
      high spin state. The enzyme was active in the metabolism of a range of model
      resorufin substrates, but exhibits highest activity towards benzyloxyresorufin.
      Indeed, this isozyme appears to play a significant role in the metabolism of this
      substrate in microsomal samples from untreated male rats. Tissue distribution
      studies indicated that CYP2C7 was expressed in liver, kidney and possibly muscle
      tissue. Cytochrome P-450 CYP2C7 could not be significantly induced by any of a
      wide range of known modulators of cytochrome P-450 expression at the mRNA level,
      however some significant changes in protein expression were observed. Some of the
      agents used (e.g., diethylnitrosamine and carbon tetrachloride) caused a
      significant reduction in the expression of this protein. In agreement with other
      reports where mRNA levels were measured we found that the level of CYP2C7 protein
      expression was sexually differentiated. Female rats express two to three times
      the level found in males, the sex difference being reversible by hypophysectomy.

PMID- 1370378
TI  - The 16S rRNA gene of Streptomyces lividans TK64 contains internal promoters.
AB  - A 632-bp Sau3AI fragment of Streptomyces lividans TK64 genome was found to confer
      promoter activity in Streptomyces and Escherichia coli. This fragment showed
      almost identical sequence (97.8%) to the S. coelicolor 16S rRNA segment
      encompassing from nucleotide 706 to 1337 region. The transcription start points
      of this fragment were identified by the primer extension method. Analysis of the
      nucleotide sequence upstream the transcription start points revealed two putative
      E. coli-like promoters resided within this fragment. The occurrence of internal
      promoters active in Streptomyces and E. coli was also confirmed in the 16S rRNA
      gene of rrnE operon from TK64.

PMID- 1370377
TI  - Electron image analysis of ribosomal subunits from Thermus aquaticus.
AB  - Electron micrographs of ribosomal subunits from the thermophilic bacterium
      Thermus aquaticus were analysed using multivariate statistical analysis and
      characteristic views constructed to reproducible spatial resolutions ranging from
      1.9 to 3.6 nm. These views were comparable to morphological classes of
      Escherichia coli ribosomal subunits, albeit with differences in fine features
      also found in archaebacterial ribosomes.

PMID- 1370376
TI  - Comparison of effects of epidermal and insulin-like growth factors, gastrin
      releasing peptide and retinoic acid on fetal lung cell growth and maturation in
      vitro.
AB  - The role in cell multiplication and maturation of several factors present in the
      late fetal lung was explored on isolated fetal rat pulmonary fibroblasts and
      alveolar epithelial type II cells cultivated in serum-free medium. The low degree
      of reciprocal contamination of each cell population was assessed by
      immunocytochemistry. Epidermal Growth Factor (EGF) stimulated thymidine
      incorporation and DNA accumulation in both cell types. In type II cells, it
      increased labeled-choline incorporation into surfactant phosphatidylcholine (PC),
      consistently with previous data obtained with lung explant cultures, but not into
      non-surfactant PC. Insulin-like growth factor (IGF)-I slightly stimulated DNA
      accumulation in fibroblasts although it did not significantly stimulate thymidine
      incorporation, contrary to IGF-II which presented a dose-dependent stimulating
      activity of thymidine incorporation. Neither IGF-I nor IGF-II stimulated type II
      cell growth. IGFs thus appear to primarily control the growth of lung mesenchyme.
      In type II cells, they stimulated the most non-surfactant PC biosynthesis.
      Gastrin releasing peptide (GRP) which was recently reported to promote fetal lung
      growth in vivo and to stimulate surfactant biosynthesis in lung organ culture
      revealed as a growth factor for type II cells only, at concentrations below 10(
      9) M. At concentration 10(-8) M, although it did not affect DNA synthesis, GRP
      tended to increase surfactant and non-surfactant-PC biosynthesis. Retinoic acid
      inhibited thymidine incorporation into type II cells on a dose-dependent manner
      but nevertheless enhanced surfactant-PC biosynthesis to a similar extent as EGF.
      It is suggested that retinoic acid may represent a differentiation or maturation
      factor for the alveolar epithelium.

PMID- 1370379
TI  - Nucleotide sequence of the complementary DNA for human Pit-1/GHF-1.
AB  - Human cDNA clones encoding Pit-1/GHF-1, a pituitary-specific DNA binding factor,
      were obtained by PCR following reverse transcription of human pituitary RNA. It
      is approx. 1.3 kb in size with 0.1 kb 5' non-coding region, 0.9 kb protein-coding
      region and 0.3 kb 3' non-coding region. The predicted human Pit-1/GHF-1 peptide
      structure has 291 amino acids and is highly conserved among mouse, rat and
      bovine. In addition, the 5' non-coding region is highly conserved with rat pit
      1/GHF-1 sequence to the transcription start site.

PMID- 1370380
TI  - Organization and nucleotide sequence of carp gonadotropin alpha subunit genes.
AB  - We have used PCR to amplify and align the sequence of two genes encoding cGTH
      alpha. Both genes comprise four exons and three introns. The organization of cGTH
      alpha genes is very similar to that of mammalian GTH alpha genes. However, the
      cGTH alpha genes only span a region of 1.2 kb which is much smaller than those
      mammalian GTH alpha genes.

PMID- 1370381
TI  - Abnormal collagen fibril structure as studied by electron microscopy.
AB  - Transmission electron microscopy has emerged as an ideal tool for the study and
      diagnosis of various disorders that involve collagen, since the information
      obtained by this technique is at the ultrastructural level. Structural
      alterations of collagen fibrils brought about by these disorders are discussed.
      The positive staining pattern of such fibrils is also investigated. In addition,
      this review describes how quantitative studies of electron-optical images from
      abnormal collagen fibrils can lead to information about the changes produced by
      collagen defects which relate to molecular or fibril architecture.

PMID- 1370382
TI  - Interleukin-11 enhances human megakaryocytopoiesis in vitro.
AB  - We investigated the effect of recombinant human interleukin-11 (rhIL-11) on human
      megakaryocytopoiesis. Nonadherent and T-cell-depleted human bone marrow (BM)
      mononuclear cells were cultured in a serum-free agar culture system. rhIL-11
      alone did not stimulate the growth of human megakaryocyte colonies. However, when
      rhIL-11 was combined with optimal or suboptimal doses of rhIL-3, the number and
      size of the megakaryocyte colonies increased. The same results were obtained when
      highly purified BM CD34-positive cells were used as target cells. Next, we
      investigated the effect of rhIL-11 on the ploidy of megakaryocytes. The ploidy
      distribution of individual cells in megakaryocyte colonies obtained by rhIL-11 in
      combination with rhIL-3 was significantly shifted towards higher values.
      Furthermore, when highly purified CD41-positive BM cells were cultured in the
      presence of rhIL-11, the ploidy distribution was shifted towards higher values.
      This effect was not suppressed by anti-IL-6 antibody. These results suggest that
      rhIL-11 acts directly as a megakaryocyte potentiator and may play a role in
      regulating human megakaryocytopoiesis.

PMID- 1370383
TI  - Role of cytokines in sustaining long-term human megakaryocytopoiesis in vitro.
AB  - An in vitro liquid suspension culture system was used to determine the role of
      cytokines in sustaining long-term human megakaryocytopoiesis. Bone marrow cells
      expressing CD34 but not HLA-DR (CD34+DR-) were used as the inoculum of cells to
      initiate long-term bone marrow cultures (LTBMC). CD34+DR- cells (5 x 10(3)/mL)
      initially contained 0.0 +/- 0.0 assayable colony-forming unit-megakaryocytes (CFU
      MK), 6.2 +/- 0.4 assayable burst-forming unit-megakaryocytes (BFU-MK), and 0.0 +/
      0.0 megakaryocytes (MK). LTBMCs were recharged every 48 hours with granulocyte
      macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha),
      IL-3, and/or IL-6, alone or in combination. LTBMCs were demidepopulated weekly or
      biweekly, the number of cells and MK enumerated, and then assayed for CFU-MK and
      BFU-MK. LTBMCs receiving no cytokine(s) contained no assayable CFU-MK or BFU-MK
      and no observable MK. LTBMCs receiving GM-CSF, IL-1 alpha, and/or IL-3 contained
      assayable CFU-MK and MK but no BFU-MK for 10 weeks of culture. The effects of GM
      CSF and IL-3, IL-1 alpha and IL-3, but not GM-CSF and IL-1 alpha were additive
      with regards to their ability to augment the numbers of assayable CFU-MK during
      LTBMC. LTBMCs supplemented with IL-6 contained modest numbers of assayable CFU-MK
      for only 4 weeks; this effect was not additive to that of GM-CSF, IL-1 alpha, or
      IL-3. The addition of GM-CSF, IL-1 alpha, and IL-3 alone or in combination each
      led to the appearance of significant numbers of MKs during LTBMC. By contrast, IL
      6 supplemented cultures contained relatively few MK. These studies suggest that
      CD34+DR- cells are capable of initiating long-term megakaryocytopoiesis in vitro
      and that a hierarchy of cytokines exists capable of sustaining this process.

PMID- 1370384
TI  - Isolation and characterization of a monoclonal antibody that recognizes the human
      c-kit receptor.
AB  - Stem cell factor (SCF) stimulates the growth of burst-forming unit-erythroid (BFU
      E) and colony-forming unit granulocyte-macrophage (CFU-GM) by binding to a
      specific cell surface receptor. The receptor for SCF is encoded by the
      protooncogene c-kit. After immunizing mice with the human erythroleukemia cell
      line OCIM1, we obtained a monoclonal antibody (MoAb) that recognizes the human c
      kit receptor. This MoAb, designated SR-1, blocks binding of 125I-human SCF to the
      c-kit receptor, and neutralizes the biologic effects of SCF in hematopoietic
      colony assays. With few exceptions, c-kit expression was identified on all
      hematopoietic and lymphoid cell lines tested by indirect immunofluorescent
      analysis using SR-1 and by binding studies with 125I-SCF. SR-1 recognizes a small
      fraction of normal bone marrow mononuclear cells, and these cells have the
      morphologic appearance of blasts. Colony assays show that BFU-E and CFU-GM
      display the c-kit receptor. SR-1 does not cross-react with murine c-kit protein,
      indicating that the binding epitopes of the human and murine c-kit receptors are
      antigenically distinct. This MoAb may be useful to characterize the spectrum of
      cells that display the c-kit receptor and to further define the role of SCF in
      hematopoiesis.

PMID- 1370385
TI  - Characterization of glycoprotein IIb/IIIa-positive cells in human umbilical cord
      blood: their potential usefulness as megakaryocyte progenitors.
AB  - A need for hematopoietic stem cells, particularly cells destined to enter the
      megakaryocyte (MK) series, prompted phenotypic analysis of mononuclear leukocytes
      in human cord blood. To this end, immunohistochemical, flow cytometric, and
      ultrastructural techniques were used. The immunogold silver enhancement method
      (IGS) for the detection of the MK-specific glycoprotein (GP) IIb/IIIa epitopes
      combined with a monocyte-specific stain for alpha-naphthyl butyrate esterase
      proved to be superior to flow cytometry (FACS) for precise quantitation of cell
      types in each sample. Immunoelectron microscopy afforded a description of
      distinctions between precursors bearing GPIIb/IIIa epitopes and other stem cells
      of the myeloid series. The number of presumed MK progenitors was surprisingly
      high, averaging 1.8% +/- 1.3% (range, 0.2% to 4.6%) by IGS and 4.1% +/- 3.0%
      (range, 0.2% to 9.3%) by FACS analysis. The occurrence of GPIIb/IIIa-positive
      denuded MK nuclei in cord blood was of interest, but was too small to affect
      these data. These observations should advocate a greater use of cord blood for
      restitution of MK/platelet-lineage-depleted patients as well as for experimental
      studies concerned with MK differentiation.

PMID- 1370386
TI  - Effects of the stem cell factor, c-kit ligand, on human megakaryocytic cells.
AB  - The kit ligand (KL), also termed stem cell factor (SCF), is a recently discovered
      hematopoietic growth factor that augments response of early progenitor cells to
      other growth factors and supports proliferation of continuous mast cell lines.
      Histological studies suggest that the receptor for SCF/KL, the c-kit proto
      oncogene product, is present in bone marrow megakaryocytes. We studied the
      effects of SCF/KL on immortalized human megakaryocytic cell lines (CMK, CMK6, and
      CMK11-5) and on isolated human marrow megakaryocytes. Human SCF/KL alone or in
      combination with the hematopoietic growth factors, interleukin-3 (IL-3),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6, stimulated
      proliferation of these megakaryocytic cell lines. SCF/KL treatment did not alter
      expression of gpIb, gpIIb/IIIa, LFA-1, ICAM-1, or GMP-140 in CMK cells. No effect
      on ploidy was observed. Furthermore, human SCF/KL induced expression of IL-1
      alpha, IL-1 beta, IL-2, and IL-6 in CMK cells. In a fibrin clot system, SCF/KL
      modestly potentiated megakaryocyte colony formation when added alone to cultures
      containing CD34+, DR+ bone marrow cells. Addition of SCF/KL with IL-3 or GM-CSF
      to these cultures resulted in a more marked marrow megakaryocytic cells. SCF/KL
      may directly affect megakaryocytopoiesis, as well as secondarily modulate
      hematopoiesis through induction of cytokines in target cells.

PMID- 1370387
TI  - Regulation of B-cell growth and immunoglobulin gene transcription by interleukin
      6.
AB  - Interleukin-6 (IL-6) stimulates growth and immunoglobulin (lg) secretion in
      Epstein-Barr virus (EBV)-infected B cells. In this study, we demonstrate that B
      cell activation by IL-6 is associated with an initial induction of c-myc, a gene
      believed to act as a competence factor for increased RNA transcription and DNA
      replication, and by increases in DNA, RNA, and protein synthesis, as well as cell
      number. IL-6 increased the levels of lg mRNA per cell in comparison to a non
      cycle-dependent cellular mRNA, tubulin. However, two other cell cycle-dependent
      cellular mRNAs, c-myc and actin, were also induced by IL-6 comparable to lg
      mRNAs. Increased levels of lg mRNA were not due to significant changes in RNA
      turnover, but appeared to reflect increased levels of RNA transcription.
      Together, these findings support the notion that IL-6 plays an important role as
      a stimulator of DNA and RNA synthesis in EBV-activated B cells.

PMID- 1370388
TI  - Clinical significance of multidrug resistance P-glycoprotein expression on acute
      nonlymphoblastic leukemia cells at diagnosis.
AB  - To evaluate the clinical value of the expression of multidrug resistance P
      glycoprotein (P-170) on the surface of acute nonlymphoblastic leukemia (ANLL)
      cells, we analyzed specimens from 150 newly diagnosed patients for staining with
      MRK16, a monoclonal antibody (MoAb) that binds to an external epitope of P-170.
      Other surface markers (CD13, CD14, CD15, and CD34) were studied by the same
      technique. A marker was considered positive when 20% or more cells were stained.
      Of 150 samples, 71 were P-170-positive. These cases did not differ from P-170
      negative cases with regard to age, sex, initial white blood cell (WBC) counts, or
      French-American-British (FAB) type (except for M3 ANLL, which were more
      frequently negative). However, leukemias arising from previous myelodysplastic
      syndrome (MDS) and therapy-induced leukemias were more frequently P-170-positive.
      CD34 and P-170 expression were significantly associated. All patients were
      treated by intensive chemotherapy. Complete remission (CR) rates were
      significantly lower in P-170-positive (23/71, 32%) than in P-170-negative cases
      (64/79, 81%) (P less than 10(-5)). CD34 positivity was also associated with a low
      remission rate (P less than 10(-5)). Survival was shorter for P-170- and CD34
      positive patients (P less than 10(-5)). The prognostic value of both markers was
      confirmed in multivariate analysis. CR duration was also shorter for P-170
      positive cases, but the difference is less significant (P = .05). It is concluded
      that P-170 analysis may be an important tool for predicting the outcome of
      intensive chemotherapy in ANLL patients.

PMID- 1370389
TI  - The gene for B7, a costimulatory signal for T-cell activation, maps to
      chromosomal region 3q13.3-3q21.
AB  - B7 is an activation antigen expressed on activated B cells and gamma-interferon
      stimulated monocytes. The B7 antigen is the natural ligand for CD28 on T cells.
      After engagement of T-cell receptor with antigen in association with major
      histocompatibility complex class II, a second signal mediated through the binding
      of B7 to CD28 greatly upregulates the production of multiple lymphokines. We have
      now mapped the B7 gene to human chromosome 3 using the technique of polymerase
      chain reaction on a panel of hamster x human somatic cell hybrid DNAs. We have
      further localized the gene to 3q13.3-3q21 using in situ hybridization on human
      metaphase chromosomes. Trisomy of chromosome 3 is a recurrent chromosome change
      seen in various lymphomas and lymphoproliferative diseases, particularly diffuse,
      mixed, small, and large cell lymphomas, human T-cell lymphotropic virus type I
      induced adult T-cell leukemia, and angioimmunoblastic lymphadenopathy. A number
      of chromosomal defects involving 3q21 have been described in acute myeloid
      leukemia and also in myelodysplastic and myeloproliferative syndromes. The
      mapping of B7 may permit further insight into disease states associated with
      aberrant lymphocyte activation and lymphokine synthesis.

PMID- 1370391
TI  - Pharmacokinetics of recombinant human granulocyte colony-stimulating factor in
      mice.

PMID- 1370390
TI  - Differential expression of cytokines in human blood monocyte subpopulations.
AB  - Cytokine expression was analyzed in CD14++ regular monocytes and in the novel
      subset of CD14+/CD16+ small monocytes. Biologic activity for tumor necrosis
      factor (TNF), interleukin-1 (IL-1), and IL-6 in the supernatant of elutriator
      enriched, cell sorter-purified small monocytes was about 10-fold lower compared
      with regular monocytes when stimulated with lipopolysaccharide (LPS) for 12
      hours. In CD14++ regular monocytes levels were 1,157 U x 10(-3)/mL, 158 U/mL, and
      1,337 U/mL for TNF, IL-1, and IL-6, respectively. By contrast, CD14+/CD16+ small
      monocytes exhibited 137 U x 10(-3)/mL, 14 U/mL, and 60 U/mL for TNF, IL-1, and IL
      6, respectively. Additional treatment with interferon-gamma enhanced production
      of TNF in both subsets, but CD14+/CD16+ small monocytes still exhibited lower
      levels. Stimulation of the monocyte subsets by platelet-activating factor gave
      the same pattern of results. Hybridization with 32P-labeled oligonucleotides
      specific for the respective cytokine messenger RNAs (mRNAs) showed a 10-fold
      lower prevalence of transcripts for TNF, IL-1, and IL-6, as well. By contrast,
      the constitutive expression of Glyceraldehyde-3-phosphate-dehydrogenase mRNA was
      1.7-fold higher in the CD14+/CD16+ small monocytes. These data indicate that the
      novel subset of small monocytes is selectively suppressed in the expression of
      the cytokines TNF, IL-1, and IL-6, suggesting that these cells may comprise a
      deactivated type of cell. The expression of class II transcripts in the small
      monocytes is, however, similar to the regular monocytes, and the cell surface
      expression of class II protein about threefold increased. Thus, the novel subset
      of small monocytes appears to be a functionally distinct type of cell.

PMID- 1370392
TI  - Use of fibrinogen to enhance the antitumor effect of OK-432. A new approach to
      immunotherapy for colorectal carcinoma.
AB  - OK-432 (5 KE), an immunomodulatory agent prepared from an attenuated strain of
      Streptococcus pyogenes, was dissolved in 1 ml of aprotinin (1000 KIE) and mixed
      with 80 mg of fibrinogen containing Factor XIII. A single intratumoral injection
      of the mixture was performed preoperatively under endoscopy in 20 patients with
      colorectal carcinoma. Postoperative histopathologic examinations revealed the
      formation of fibrin fibers at the site of injection and marked infiltration of
      inflammatory cells into the tumor stroma on the day after injection; the
      formation of granulomas containing many giant cells after 4 to 7 days; and
      extensive regression of tumor tissue after 14 days. This study suggests that the
      high concentration of exogenous fibrinogen gelatinized enough to trap OK-432 in
      tumor stroma and that OK-432 induced granulomatous hypersensitivity to degenerate
      tumor stroma, thereby causing regression of the tumors.

PMID- 1370393
TI  - Alternating non-cross-resistant chemotherapy for non-Hodgkin's lymphoma of
      intermediate-grade and high-grade malignancy. A pilot study.
AB  - Thirty-two patients with advanced non-Hodgkin's lymphoma (NHL) with aggressive
      histologic findings were treated with cyclophosphamide, doxorubicin, methotrexate
      with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide, and
      prednisolone (CAMBO-VIP), in which presumably non-cross-resistant
      myelosuppressive and nonmyelosuppressive agents were administered during
      alternate weeks for 12 weeks. To ensure the high-dose intensity of the protocol,
      dose reduction and delay in treatment were minimized. Three patients were treated
      inadequately. Twenty-six (89.7%) of 29 evaluable patients had a complete
      response, and three had a good partial response. Relapse occurred in four
      patients, with a median follow-up of 29 months. The actuarial overall survival
      and disease-free survival were estimated to be 87.6% and 75.9%, respectively. The
      CAMBO-VIP treatment was well tolerated; myelosuppression was severe but transient
      and caused no serious infections. Side effects that affected dose intensity were
      oral ulceration, occurring in 28 patients, and blister formation under the
      thickened skin of palms and/or soles, followed by desquamation (5 patients).
      Hepatic toxicity was generally mild to moderate; it was severe in one patient. A
      12-week regimen of CAMBO-VIP was effective for advanced NHL with aggressive
      histologic findings.

PMID- 1370394
TI  - Choroid plexus tumors in childhood. Response to chemotherapy, and
      immunophenotypic profile using a panel of monoclonal antibodies.
AB  - Clinical and immunophenotypic (IP) data are presented on three children with
      choroid plexus (CP) tumors. Two children ages 0.2 and 2 years old with
      histologically proven malignant tumors had subtotal tumor resections and were
      treated with ten monthly cycles of eight-drugs-in-1-day chemotherapy without
      radiation therapy (XRT). Both are free of tumor 4 and 7 years later. The
      literature on survival of children with CP carcinomas after chemotherapy and XRT
      is reviewed. Monoclonal antibodies to 17 neuroectodermal, neuronal, glial, and
      leukocytic markers on frozen sections were used to IP the two malignant tumors
      and a CP papilloma. All tumors expressed two neuroectodermal markers (PI-153/3
      and UJ 223.8), cytokeratin 19, and a neural and leukocyte marker (Thy-1). Two of
      three expressed neurofilament protein (NF-H) and glial fibrillary acidic protein
      (GFAP) and one expressed NF-M and common leukocyte antigen. None had strong
      expression for the panneuroectodermal antigen UJ13/A. There was variable
      expression of the other markers. The most common IP profile for CP tumors
      (cytokeratin 18+, PI-153/3+, Thy-1+, UJ 223.8+, and GFAP+ and UJ13A-, UJ 127.11-,
      and NF-L-) is discussed in the context of the current knowledge of the
      ontogenetic origin of the CP. It was concluded that chemotherapy for malignant CP
      tumors can be associated with long-term survival in young children and that the
      unique IP profile of CP tumors with coexpression of three intermediate filaments
      suggests new and provocative evidence of their cellular complexity and
      heterogeneity.

PMID- 1370396
TI  - Identification of a CD21 receptor-deficient, non-Ig-secreting peripheral B
      lymphocyte subset in HIV-seropositive drug abusers.
AB  - We have studied 61 HIV-seropositive heroin addicts (18 asymptomatic, 20 ARC, and
      23 AIDS cases), 26 HIV-seronegative heroin addicts, and 45 healthy blood donors,
      matching the groups each other for age and sex. We have focused on the phenotypic
      characteristics of B subpopulations in the peripheral blood of HIV-seropositive
      and -seronegative drug abusers, paying particular attention to the consistence of
      the "CD20+" B cell subset, which poorly expresses the CD21 membrane receptor for
      the C3d and Epstein-Barr virus (EBV) (referred to as "CD20 + CD21-" subset). In
      healthy blood donors, the ratio CD20 + CD21-/CD20+ x 100 is extremely low (mean
      +/- SEM = 8.1 +/- 0.9) and rarely exceeds the value of 20. On the contrary, in
      HIV seropositives, the values are much more dispersed, with higher mean values
      (mean +/- SEM = 25.8 +/- 1.8) ranging from 50 to 60. An intermediate situation
      characterizes the class of HIV-seronegative heroin addicts, whose values are
      slightly higher and more dispersed than that of normal controls (mean +/- SEM =
      11.6 +/- 1.3). The extent of the amplification of the CD20 + CD21- subset in HIV
      seropositive individuals does not apparently correlate with the progression of
      the disease and represents an early event in the clinical course of HIV
      infection. For each subject of the study group, the number of CD20 + CD21- B
      lymphocytes is not correlated to other early markers of HIV infection, as the T4
      lymphocyte number, or total Ig levels in sera. A functional characterization of
      the CD20 + CD21- B cell subset indicates that, in HIV-seropositive patients,
      these cells are unable to produce specific and nonspecific immunoglobulins
      (Ig's), either spontaneously or after pokeweed mitogen stimulation. Furthermore,
      this cell subset is characterized by poor expression of surface Ig's. The data
      reported suggest that this cell subset can be regarded as situated at an early
      level of B cell lineage differentiation.

PMID- 1370395
TI  - Cytoskeletal changes in hepatocytes induced by Microcystis toxins and their
      relation to hyperphosphorylation of cell proteins.
AB  - The heptapeptide toxins produced by the blue-green alga (cyanobacterium)
      Microcystis aeruginosa are selectively hepatotoxic in mammals. The characteristic
      post-mortem pathology of the liver is extensive lobular disruption due to
      sinusoidal breakdown, leakage of blood into the tissue and hepatocyte
      disintegration. Isolated hepatocytes incubated with toxin show severe structural
      deformity and surface blebbing. This paper demonstrates the effects of
      Microcystis toxins on the contraction and aggregation of actin microfilaments,
      and on the relocation and breakdown of cytokeratin intermediate filaments, in
      cultured hepatocytes. Earlier work did not show changes in the
      assembly/disassembly of actin; however, this paper demonstrates the change in
      cytokeratin from intermediate filaments to distributed granules in the cytoplasm
      of toxin-affected cells. Acrylamide gel electrophoresis of cytoskeletal fractions
      from hepatocytes did not show changes in total cytokeratins; however, marked
      changes in the immunogenicity of cytokeratins at 52 and 58 kDa were seen on toxin
      exposure of cells. Measurement of 32P-phosphorylation of proteins in toxin
      affected cells incubated with [32P]orthophosphate showed a dramatic increase
      compared to control incubations. This is in agreement with research elsewhere
      describing phosphatase inhibition in vitro by Microcystis toxins. The data
      indicate that phosphorylated cytokeratin is a major component of cytoplasmic
      fraction phosphorylated protein after toxin exposure to hepatocytes. It is
      concluded that the mechanism of Microcystis toxicity to the hepatocyte is through
      cytoskeletal damage leading to loss of cell morphology, cell to cell adhesion and
      finally cellular necrosis. The underlying biochemical lesion is likely to be
      phosphatase inhibition causing hyperphosphorylation of a number of hepatocyte
      proteins, including those cytokeratins responsible for microfilament orientation
      and intermediate filament integrity.

PMID- 1370397
TI  - [Asthenia in tumor patients].

PMID- 1370398
TI  - Human VEP contrast modulation sensitivity: separation of magno- and parvocellular
      components.
AB  - Human cortical visual evoked potentials (VEPs) were retrieved in real time
      (without averaging). The stimuli were sinusoidal gratings whose contrast was
      temporally modulated about some mean value. Electrophysiologically determined
      contrast modulation thresholds were measured at standing contrast over the range
      from 2.5% to 50%, defining an increment threshold function. Increment threshold
      functions were obtained under two different spatio-temporal stimulus conditions
      identified as "sustained" (4 c/deg grating modulated at 1.5 Hz) and "transient"
      (1 c/deg grating modulated at 20 Hz). Under each of these conditions, threshold
      responses were retrieved at both the fundamental and second harmonic of the
      contrast modulation frequency. Under "sustained" conditions log increment
      threshold responses and the fundamental the second harmonic of the modulation
      frequency were similar to those at the fundamental except for a saturation effect
      (i.e., above a mean contrast of 25% there was little further reduction in
      modulation sensitivity). There was no contrast gain control under "transient"
      stimulus conditions. In other words, the same absolute amount of contrast change
      produced threshold responses for all mean levels up to 25%. This was true at both
      the fundamental and second harmonic of the modulation frequency. Stimulus
      differences produce striking differences in the electrophysiologically inferred
      increment threshold function for grating contrast, but fundamental and second
      harmonic evoked responses reflect processes with similar increment threshold
      behavior.

PMID- 1370399
TI  - The influence of pattern size on amplitude, latency and wave form of retinal and
      cortical potentials elicited by checkerboard pattern reversal and stimulus onset
      offset.
AB  - Transient pattern electroretinograms (PERGs) and visual evoked potentials (VEPs)
      were recorded with checkerboard pattern reversal and equiluminance stimulus onset
      offset, elicited by a high quality moving mirror stimulator. Different sized
      checkerboard patterns (0.35-4.2 c/deg) were used as stimulus patterns. The wave
      forms of the equiluminance stimulus onset responses were similar to ERGs evoked
      with luminance decrease and the stimulus offset PERGs were like ERGs elicited by
      luminance increase. The PERG c wave and the VEP showed spatial frequency tuning
      with pattern reversal and stimulus offset. Spatial frequency tuning was not
      detectable with PERG a and b waves. Pattern reversal and stimulus onset evoked
      PERGs had no major spectral components above 40 Hz; stimulus offset evoked PERGs
      contained components up to 55.3 Hz. Retino-cortical time--measured as a latency
      difference of the PERG b wave to VEP P100--was identical with pattern reversal
      and stimulus onset and about 12 msec longer with stimulus offset. Our results
      suggest that the 3 stimulation modes, reversal, onset and offset induce different
      types of processing at the retinal and cortical levels. PERG a and b waves to our
      high luminance/contrast stimuli contain no pattern specific information and the c
      waves are the sum of luminance and pattern specific responses.

PMID- 1370400
TI  - Sequence-dependent deterioration in the visual evoked potential in the absence of
      drowsiness.
AB  - When visual evoked potentials (VEPs) are tested patients are often expected to
      focus on a pattern screen for prolonged periods of time. This may lead to
      fatigue, failure of concentration and drowsiness, and consequently to a
      deterioration in the recorded VEP. To determine whether there may be time
      dependent changes in the VEP of normal subjects independent of the degree of
      alertness, attention and altertness were controlled using a reaction time (RT)
      task in which the subjects were required to re-illuminate the fixation point in
      the middle of the stimulating screen for the VEP. It was first established that
      the switching of the fixation point produced little contamination of the
      background VEP to pattern reversal and that the latency and amplitude of P100 to
      pattern reversal were identical whether or not the subject was engaged in the RT
      task. A sequence of 16 averages of the VEP to 256 pattern reversals was recorded,
      alternately with or without the RT task. The measured RTs decreased during the
      sequence, presumably due to practice. There was a progressive decrease in the
      amplitude N70-P100, accompanied by an increase in the variability of the latency
      of P100. These changes cannot be attributed to lack of alertness, given the
      improvement in RT. Clinicians should be aware of the possibility of a
      deterioration in the VEP due to physiological mechanisms when the testing
      protocol involves multiple averages.

PMID- 1370401
TI  - Somatosensory evoked potentials in the term newborn.
AB  - Median nerve somatosensory evoked potentials (SEPs) were recorded from surface
      electrodes in 40 healthy term infants (range 36.5-43 weeks postmenstrual age).
      Electrical stimulation at 5 Hz was used, averaging the response to several runs
      of 1024 stimuli to each median nerve, bandpass 10-3000 Hz, sweeptime 100 msec.
      Identifiable potentials were collected over the cervical cord on all runs in all
      40 infants and from the cortex in at least some runs in 39 out of 40 infants. The
      cervical response showed little variation and consisted of a clear negative wave
      with up to 3 peaks, mean latency of the largest 10.2 +/- 0.7 msec, followed by a
      positive deflection. The cortical response was very variable in form and latency
      between infants and to a lesser degree within infants. Four types of cortical
      wave form were found, symmetrical, asymmetrical, plateau and M shaped, of
      increasing complexity. In 11% of trials the response was absent or indistinct but
      could usually be uncovered by alteration in stimulus frequency or intensity. In
      the whole group, the mean latency for N1 was 30.0 +/- 6.8 msec and for the
      central conduction time 19.8 +/- 6.5 msec. Significant differences were found
      between the 4 cortical wave forms in the main variables measured, which gave
      support for form S being the most primitive and form M the most mature response.

PMID- 1370402
TI  - The late somatosensory evoked potential in premature and term infants. I.
      Principal component topography.
AB  - Very little is known about the topographic distribution of the cortical
      somatosensory evoked potential in premature infants. Principal component analysis
      (PCA) was applied to the wave forms generated from right median nerve stimuli
      over a relatively long sweep (483 msec post stimulus) at 16 electrodes in 53
      infants with postconceptual ages from 31 to 40 weeks, subdivided into 5 groups by
      2 week increments. Factor scores were averaged across subjects, within groups and
      displayed as topographical maps. Four factors accounted for 71-76% of the
      variance in each of the 5 groups and the factors extracted from the PCA performed
      independently in each group were markedly consistent. The first factor (N1/P1)
      had a left posterior minimum and a left frontal-central maximum and probably
      represents a tangential dipole located in the post-central gyrus. The second
      factor (N2) was characterized by a consistent left central minimum with a
      systematic developmental change in the maximum that seemed to imply that its
      neural generator was changing in orientation as the infants matured. A third
      factor (N3) accounted for the most variance and appeared to represent the first
      evidence of activity in the ipsilateral cortex. Finally, a very late fourth
      factor appeared only in the more mature groups, with uncertain localization. The
      topographic maps of the factor scores for these 4 factors appear to account for
      independent generators in the SEP of the premature and term infant.

PMID- 1370403
TI  - The late somatosensory evoked potential in premature and term infants. II.
      Topography and latency development.
AB  - The maturation of latency and scalp voltage topography of the simultaneously
      bilateral somatosensory evoked potential was studied in 53 neurologically intact
      pre-term and term infants, from 31 to 40 weeks post-menstrual age. Four peaks
      (N1, P1, N2 and P2) were reliably identified in all infants. The latency of each
      peak decreased as the infants matured. Each peak had a unique voltage scalp
      topography that remained stable as infants matured, even though the maps changed
      in amplitude intensity. N2 was large, easily identifiable with a central peak,
      and extremely stable in topography, suggesting that it might be used to evaluate
      the functional status of the somatosensory cortex in pre-term and term infants
      who are at high risk for developing intracranial hemorrhage leading to
      abnormalities of tone and delays in motor development.

PMID- 1370404
TI  - Dermatomal somatosensory evoked potentials: cervical, thoracic, and lumbosacral
      levels.
AB  - Somatosensory evoked potentials were recorded at the scalp to stimulation of the
      skin at C4, C5, C6, C7, C8, T2, T4, T6, T8, T10, T12, L2, L3, L4, L5, and S1
      dermatomes and of the tibial nerve. Stimulation and recording techniques are
      described. Data were obtained from 41 normal subjects, 25 of which had all 16
      dermatomes studied. Wave form descriptions include both typical and atypical
      presentations. Descriptive statistics for latency, amplitude, left to right
      comparisons, and level to level comparisons are given. Scalp response latencies
      for distal extremity dermatomes were well correlated with height but not with
      vertebral column length, whereas latencies for thoracic dermatomes were not well
      correlated with either height or vertebral column length. Since scalp response
      amplitude data were not normally distributed, they were logarithmically
      transformed and minimum and maximum limits for 1 S.D., 2 S.D., and 3 S.D.
      derived. Left/right amplitude ratios were similarly treated. Level to level
      comparisons were achieved with a Z score concordance analysis, which showed that
      the response values at one level can be used to predict the response values at
      another level.

PMID- 1370405
TI  - Unmasking of cortical SEP components by changes in stimulus rate: a topographic
      study.
AB  - We performed topographic mapping of somatosensory responses to median nerve
      stimulation delivered at 2, 5 and 10 Hz. Parietal N20 was significantly
      attenuated in 10 Hz somatosensory evoked potentials (SEPs), while central P22
      diminished between 2 and 5 Hz, remaining stable thereafter. The single component
      most affected by increasing stimulus rate was N30, which abated by more than 50%
      in 10 Hz SEPs, as compared with basal responses. N30 attenuation disclosed the
      existence of an earlier negative component, N24, which appeared as a notch on the
      N30 ascending slope in 2 Hz SEPs, but became a well-defined peak at higher
      stimulus rates. The N24 negativity was not significantly modified by stimulus
      rate; it had a parietal counterpart (P24) with the same peak latency and
      identical behavior during the experimental procedure. Both P24 and N24 could be
      differentiated from central P22 on the basis of topographical distribution and
      response to stimulus frequency. P22 topography could be the result of a radially
      oriented generator, while P24/N24 appeared as the two poles of a neural source
      tangential to the scalp. P27 was seen in 40% of the subjects only; it is
      suggested that P27 is itself a composite potential to which the generator of N30
      could contribute in part. We conclude that there is no single "optimal"
      stimulation rate for SEP recording. On the contrary, combination of different
      frequencies of stimulation should enhance the diagnostic utility of this
      technique by allowing a more selective assessment of overlapping activities.

PMID- 1370406
TI  - Differences in human evoked potentials related to olfactory or trigeminal
      chemosensory activation.
AB  - The aim of the present study was to determine, whether there are differences in
      the topographical distribution of chemosensory evoked potentials (CSEPs) due to
      stimulation with different odorous substances. The odorants used in the study
      which mainly excited the olfactory nerve were vanillin and acetaldehyde; those
      which additionally excited the trigeminal nerve were sulphur dioxide and ammonia.
      Twelve subjects participated in the study. The subjects separately estimated the
      intensity of the odorous and of the painful/pricking sensation caused by the
      stimuli, and described the odorous qualities in their own words. CSEPs were
      recorded from 7 positions. After stimulation with "olfactory" substances maximum
      CSEP amplitudes were recorded at parieto-central sites, and after stimulation
      with "trigeminal" substances maximum amplitudes were obtained at the vertex.
      Following stimulation with ammonia and sulphur dioxide amplitudes were largest
      contralateral to the stimulated nostril. In contrast, little difference in CSEP
      amplitudes was observed between hemispheres after stimulation with vanillin or
      acetaldehyde. Thus, the topographical distribution of CSEP amplitudes may provide
      information with regard to the sensory system (olfactory or trigeminal) activated
      by the presentation of an odorous stimulus.

PMID- 1370407
TI  - Human auditory evoked potentials recorded using maximum length sequences.
AB  - A maximum length sequence (MLS) is a specially constructed pseudorandom binary
      sequence that can be used to control the presentation of sensory stimuli. The
      evoked potentials to such a sequence of stimuli can be analyzed to give the
      response to one stimulus in the sequence. This procedure allows auditory evoked
      potentials to be recorded at stimulus rates that would cause a confusing overlap
      of responses with regular averaging. The MLS technique can be used with auditory
      evoked potentials at all latencies although it is most effective for the brain
      stem and middle-latency responses. By demonstrating different refractory periods
      for different parts of the response, the technique may help delineate the
      component structure of the evoked potential. As well, an MLS analysis can
      disentangle the auditory brain-stem response from overlapping middle-latency
      responses during evoked potential audiometry.

PMID- 1370408
TI  - Determinants on simian virus 40 large T antigen are important for recognition and
      phosphorylation by casein kinase I.
AB  - Casein kinase I has been shown to phosphorylate Ser123 and possibly Thr124, in
      simian virus 40 (SV40) large T antigen; the same sites are also modified in
      cultured cells incubated with 32Pi [Friedrich A. Grasser, Karl H. Scheidtmann,
      Polygena T. Tuazon, Jolinda A. Traugh & Gernot Walter (1988) Virology 165, 13
      22]. The peptide, A-D-S-Q-H-S-T-P-P, which corresponds to the amino acid sequence
      118-125 of SV40 large T antigen, was synthesized together with peptides
      containing changes in specific amino acid residues on either side of Ser123.
      These peptides were used as model substrates to determine the amino acids in the
      SV40 large T antigen important for recognition by casein kinase I. The native
      peptide identified above, with aspartate at the -4 position, was a poor substrate
      for casein kinase I in vitro. Peptides with acidic residues added at the -2 and 
      3 positions, preceding Ser123, were phosphorylated by casein kinase I with
      apparent Km values around 2 mM and Vmax values up to 500 pmol.min-1.ml-1. When
      acidic residues were added at both sides of the phosphorylatable serine, the
      peptide had a first-order rate constant over 20-fold higher than peptides with
      acidic amino acid residues at the N-terminus only; the apparent Km value was 0.65
      mM with a Vmax of 2900 pmol.min-1.ml-1. The effects of modifying Ser120 to
      phosphoserine were examined by addition of a recognition sequence for the cAMP
      dependent protein kinase prior to Ser120. Prior phosphorylation of the peptide at
      Ser120 lowered the apparent Km to 0.061 mM and increased the Vmax to 360 pmol.min
      1.ml-1, a 50-fold decrease in Km for casein kinase I and a 6-fold increase in
      Vmax as compared to the non-phosphorylated peptide. This indicates that Ser120,
      which has been shown to be phosphorylated in vivo, provides an appropriate
      recognition determinant for casein kinase I.

PMID- 1370409
TI  - Interleukin 1 beta and tumour necrosis factor alpha induce a macrophage-type of
      nitric oxide synthase in rat renal mesangial cells.
AB  - Treatment of mesangial cells with interleukin 1 beta (IL-1 beta) or tumour
      necrosis factor alpha (TNF alpha) has been shown to increase cGMP formation, most
      probably due to induction of nitric oxide synthase. Here we report that maximum
      stimulation of cGMP formation over a 24-h period required the presence of IL-1
      beta or TNF alpha during the first 18 h of induction. N4-monomethyl-L-arginine (L
      NMMA) was a potent inhibitor of cytokine-induced cGMP formation while N4-nitro-L
      arginine (L-NNA) was less active. Formation of nitric oxide was detected in the
      cytosol of cytokine-treated mesangial cells by activation of purified soluble
      guanylate cyclase and was stimulated by tetrahydrobiopterin, but not by calcium
      calmodulin. Treatment of cells with IL-1 beta or TNF alpha markedly attenuated
      the contractile response to a subsequent challenge with angiotensin II.
      Furthermore, conditioned medium from IL-1 beta-treated cells increased cGMP in
      untreated control cells.

PMID- 1370410
TI  - Differential responses to interleukin 2 define functionally distinct subsets of
      human natural killer cells.
AB  - Human natural killer (NK) cells can be subdivided into two populations based on
      the density of cell surface CD56 antigen. The great majority (approximately 90%)
      of NK cells express CD56 at low levels (the CD56dim phenotype), whereas a small
      NK cell subset (approximately 10%) exhibits approximately fivefold greater
      density of surface CD56. Exposure to exogenous interleukin 2 (IL 2) induces
      tenfold greater proliferation of CD56bright cells compared to CD56dim
      lymphocytes, even though both subsets constitutively express similar levels of
      intermediate affinity IL 2 receptor (IL 2R) p75 chains. Incubation with IL 2
      alone or irradiated target cells alone could induce expression of the IL 2R p55
      chain by both CD56bright and CD56dim NK cells; a combination of both stimuli was
      most effective. IL 2R p55 induction was evident after co-culture of NK cells with
      both NK-sensitive and NK-resistant cell lines or with antibody-coated target
      cells. Activation of NK cells with IL 2 plus target cells resulted in enhanced
      proliferation compared to activation with IL 2 alone; target cells alone did not
      induce significant proliferation. Although both NK cell subsets appeared to
      express high-affinity IL 2R p75/p55 heterodimers after stimulation with target
      cells and IL 2, proliferation of CD56dim cells remained minimal after such
      activation; activated CD56dim cells consistently demonstrated less proliferation
      to IL 2 than did resting CD56bright cells. In contrast, CD56bright NK cells
      exhibited even greater proliferation after stimulation with target cells. Almost
      all CD56dim NK cells expressed CD16 (Fc gamma R III) as well as the NK zeta
      chain, whereas less than 50% of CD56bright cells express either CD16 or zeta.
      CD56bright and CD56dim lymphocytes, thus, appear to represent distinct
      subpopulations of NK cells with different functional activities. Unlike
      CD56bright cells, CD56dim NK cells do not proliferate optimally to IL 2, even
      after the latter have been stimulated to express both IL 2R p55 and IL 2R p75.
      Efficient proliferation of CD56dim NK cells may, thus, require additional or
      alternative signals.

PMID- 1370411
TI  - Binding of a major T cell epitope of mycobacteria to a specific pocket within HLA
      DRw17(DR3) molecules.
AB  - CD4+ T cells recognize antigenic peptides bound to the polymorphic peptide
      binding site of major histocompatibility complex (MHC) class II molecules. The
      polymorphism of this site is thought to dictate which peptides can be bound and
      thus presented to the T cell receptor. The mycobacterial 65-kDa heat-shock
      protein (hsp65) peptide 3-13 is an important T cell epitope: it is immunodominant
      in the mycobacterium-specific T cell response of HLA-DR3+ individuals but,
      interestingly cannot be recognized in the context of any other HLA-DR molecules.
      We, therefore, have tested whether the hsp65 epitope p3-13 is selected for T cell
      recognition in the context of only HLA-DR3 molecules by an unique binding
      specificity for HLA-DR3. Using biotinylated peptides and EBV-transformed BLCL
      comprising all known HLA class II specificities, we find that p3-13 binds to HLA
      DRw17(DR3) but not to any other HLA-DR molecule. Conversely, a control peptide
      p307-319 influenza hemagglutinin binds to all known HLA-DR molecules but only
      weakly to HLA-DRw17 and HLA-DR9. Peptide binding could be inhibited by excess
      unbiotinylated competitor analogue as well as by anti-DR monoclonal antibodies
      but not by anti-class I-, anti-DP- or anti-DQ monoclonal antibodies. The amino
      acid sequence of DRw17 molecules differs uniquely at five positions from the
      other DR beta 1 sequences. Three of these five residues (positions 26, 71 and 74)
      are potential peptide contacting residues. These residues map closely together in
      the hypothetical three-dimensional model of the DR molecule and, thus, most
      probably form a positively charged pocket, critical for the binding of p3-13.
      Interestingly, p3-13 does not bind to a DR3 variant, the DRw18 molecule. The
      DRw18 beta 1 chain differs from DRw17 at two major positions, close to or within
      the DRw17-specific pocket. These substitutions drastically change the structure
      and charge of the pocket and thus presumably abrogate its ability to bind p3-13.

PMID- 1370412
TI  - Age-associated increase in number of CD4+CD8+ intestinal intraepithelial
      lymphocytes in rats.
AB  - A significant number of CD4+CD8+ T cells were detected in intestinal
      intraepithelial lymphocytes (IEL) of various strains of rats including Wistar,
      WKA, BN, LEW and F344. The site of the CD4+CD8+ population in IEL increased with
      age in all strains we examined. Most IEL bearing CD8 expressed no CD5 antigen in
      young rats, while all CD4+CD8+ IEL and some of CD8+ IEL in aged rats were of
      CD5+CD45RB- phenotype. In germ-free Wistar rats, age-associated increase in the
      number of CD4+CD8+CD5+ IEL was not evident, indicating that stimulation by the
      intestinal microflora was important for expansion of the CD4+CD8+CD5+CD45RB- IEL.
      Aged athymic F344 nude rats contained appreciable numbers of CD4+ IEL and CD8+
      IEL but few CD4+CD8+ IEL, suggesting that the CD4+CD8+ IEL may be derived from
      thymus-dependent populations. Unlike a majority of CD4+CD8+ thymocytes bearing a
      low intensity of CD3/T cell receptor (TcR) alpha/beta, the CD4+CD8+ T cells in
      IEL expressed a high intensity of CD3/TcR alpha/beta on their surface. The
      CD4+CD8+ IEL appear to contribute to the spontaneous proliferation of the IEL in
      aged rats as assessed by tritiated thymidine incorporation after in vitro culture
      with medium only. These results suggest that with aging a unique CD4+CD8+ IEL may
      expand at a local site of the intestine under the influence of intestinal
      microflora and may contribute to the first line of defense against various
      pathogens in the epithelium.

PMID- 1370413
TI  - Sequence variation of cytotoxic T cell epitopes in different isolates of Epstein
      Barr virus.
AB  - Previous results have identified two distinct cytotoxic T lymphocyte (CTL)
      epitopes encoded by Epstein-Barr virus (EBV), TETA (ORF BLRF3/BERF1 residues 329
      353) and EENL (ORF BERF3/BERF4 residues 290-309). Measurement of the
      specificities of CTL clones (TETA-specific clone 13 and EENL-specific clone 7)
      directed against these epitopes indicated that the EENL epitope is conserved in
      all strains of EBV tested while the TETA epitope varied between individual virus
      strains. Sequencing of the DNA regions encoding these two CTL epitopes in
      different EBV isolates confirmed these interpretations and demonstrated that
      different TETA epitope sequences were encoded by B-type EBV strains and by the
      B95-8 isolate of EBV compared to the other A-type EBV strains. Titration of
      synthetic variants of the TETA epitope revealed that the epitope encoded by B95-8
      was 15-fold less efficient as a T cell epitope than the sequence encoded by other
      A-type viral strains while the TETA variant encoded by the B-type strains
      displayed essentially no activity as a T cell epitope.

PMID- 1370414
TI  - The specificity of recognition of a cytotoxic T lymphocyte epitope.
AB  - An Epstein-Barr virus (EBV)-specific CD8+ cytotoxic T lymphocyte (CTL) clone
      (LC13) was shown to recognize the minimal peptide determinant FLRGRAYGL from the
      EBNA 3 antigen of the BL74 strain of EBV. The equivalent epitope from the B95-8
      strain (FLRGRAYGI) is not recognized when endogenously presented and the peptide
      is 15-fold less active than FLRGRAYGL. A replacement set of peptides was
      synthesized in which each residue within FLRGRAYGL was sequentially replaced with
      all other genetically coded amino acids. These peptides were tested for their
      ability to sensitize target cells to lysis by LC13. Of the 171 single-amino acid
      replacement peptides only 15 were more active than the peptide FLRGRAYGI. Five
      peptides had significantly greater activity than FLRGRAYGL and a peptide
      incorporating the most active of these single-amino acid substitutions
      (HIRGRAYSL) induced lysis at concentrations approximately 30-fold less than
      FLRGRAYGL. Simplified theoretical calculations based on this study suggest that
      CTL LC13 has a specificity for its target epitope of 1 in 4.7 x 10(10). This
      represents the first complete analysis of the role of single amino acids within a
      minimum epitope on the specificity of CTL recognition.

PMID- 1370415
TI  - The CD56 adhesion molecule is the major determinant for detecting non-major
      histocompatibility complex-restricted cytotoxic mononuclear cells from the
      intestinal lamina propria.
AB  - In this study, specific antibodies against natural killer (NK) cell surface
      markers identify these cells to be commonly present in normal intestinal mucosa
      of inflammatory bowel disease (IBD) and carcinoma patients. Cells expressing the
      CD56 adhesion molecule were found to be far more abundant than CD16+ cells.
      Functional studies revealed that cells mediating non-major histocompatibility
      complex-restricted cytotoxicity (NK activity) in the lamina propria express the
      CD56 surface antigen, whereas only a minority of this activity resides in the
      population with CD16 expression. This is in contrast with peripheral blood NK
      cells, which were found to be almost exclusively both CD16+ and CD56+. Moreover,
      in the lamina propria of the intestine we found CD3+ T lymphocytes not to be
      involved in spontaneous cell-mediated killing of tumor cells. Considerably higher
      numbers of cells with the CD16 or CD56 surface markers were found to be present
      in normal mucosa of IBD patients compared with normal mucosa of carcinoma
      patients, which was also reflected in higher levels of cytotoxicity detected in
      lamina propria mononuclear cell preparations from normal IBD mucosa. Because of
      the disease-related localization of the mucosa studied from both patient groups,
      i.e. ileum vs. colon, the observed differences may be related to tissue
      characteristics. Within the IBD group, relatively high levels of cytotoxicity
      were found in cell preparations from normal mucosa of Crohn's disease patients
      compared with ulcerative colitis patients, which might support the current
      concept that Crohn's disease affects the whole of the gastrointestinal tract.

PMID- 1370416
TI  - Induction of experimental autoimmune encephalomyelitis by native myelin basic
      protein-activated T lymphocyte lines.
AB  - Self antigens bind to MHC class II molecules in vivo. The capacity of class II
      molecules to bind native self antigen, namely antigen that has not been processed
      through an endososomal pathway, could increase susceptibility to autoimmune
      diseases if recognized by autoreactive T lymphocytes. To confirm this prediction
      we designed experiments to show that: (a) native myelin basic protein (BP)
      activates encephalitogenic T lymphocyte lines, and (b) these activated lines
      cause experimental autoimmune encephalomyelitis (EAE) in naive rats. We show that
      two encephalitogenic T lymphocytes lines, LEW and BN, are activated by native BP
      in the presence of paraformaldehyde pre-fixed antigen-presenting cells (APC). The
      degree of activation, as measured by T lymphocyte proliferation, was equal to
      that obtained in response to BP processed by APC prior to paraformaldehyde
      fixing. The response to native BP was confirmed by demonstrating insensitivity to
      the presence of the lysosomotropic agent chloroquine or protease inhibitors.
      Activation of T lymphocytes by BP required the presence of syngeneic APC. The
      activated T lymphocyte lines were injected into naive recipient rats that
      developed EAE within 5 days. Both disease incidence and severity were equal to
      that observed in rats that were treated with T lymphocytes activated by processed
      BP. Hence, at least in EAE, the risk of an autoimmune event could be precipitated
      by a complex of native antigen and class II molecules on cells that do not
      possess an endososomal pathway for antigen processing and presentation.

PMID- 1370417
TI  - Specificity and T cell receptor beta chain usage of a human collagen type II
      reactive T cell clone derived from a healthy individual.
AB  - Collagen type II (CII) is a cartilage-specific matrix compound well known as an
      inducer of an experimental, T cell-dependent autoimmune arthritis, a disease
      which shows some similarities to human rheumatoid arthritis. Here we report on an
      HLA-DR7-restricted human CD4 T cell clone (TC9), which was isolated from a
      healthy donor and recognizes human CII. After screening CNBr fragments of CII and
      tryptic fragments derived thereof, the T cell epitope could be mapped to amino
      acid residues 271-285 of the triple helical region of CII that are located within
      CNBr fragment 11 [alpha 1 (II) CB11]. This epitope was confirmed by a synthetic
      peptide stimulatory for TC9. The T cell receptor beta chain of TC9 was cloned
      using the polymerase chain reaction; it comprises V beta 6.7 and contains besides
      J beta 2.3 and C beta 2 an as yet undescribed sequence for the D segment.

PMID- 1370418
TI  - American Leishmania spp. and Trypanosoma cruzi: galactosyl alpha(1-3) galactose
      epitope localization by colloidal gold immunocytochemistry and lectin
      cytochemistry.
AB  - Patients with Chagas' disease or different clinical forms of leishmaniasis
      (cutaneous or visceral) have elevated galactosyl alpha (1-3)galactose antibodies.
      Using colloidal gold immunocytochemistry--monoclonal antibody gal-13 (specific
      for lipid-linked galactosyl alpha (1-3)galactose residues) and anti-nidogen
      antibodies and lectin cytochemistry (Bandeiraea simplicifolia IB4), both
      techniques specific for demonstrating galactosyl alpha (1-3)galactose residues-
      we have found terminal disaccharide residues on the Trypanosoma cruzi external
      surface of Vero cell-derived trypomastigotes but not in intact epimastigotes
      (although disrupted epimastigotes strongly stained), in the lips of the flagellar
      pocket, and on the parasitic side exactly opposite to the flagellar pocket in
      amastigote and promastigote forms of American Leishmania. These results resemble
      those obtained using anti-laminin antibodies in both trypanosomatids. In
      addition, results obtained with anti-nidogen antibodies seem to recognize in
      Trypanosoma cruzi and American Leishmania culture forms another different unknown
      terminal disaccharide. These results confirm the presence of terminal galactosyl
      alpha (1-3)galactose residues in both trypanosomatids, and that rabbit anti
      laminin antibodies are indeed also recognizing galactosyl alpha (1-3)galactose
      residues as demonstrated for human circulating antibody. The presence of abundant
      galactosyl alpha (1-3)galactose residues on Trypanosomatid family members
      suggests a specific unknown role in parasite physiology for this terminal
      disaccharide.

PMID- 1370419
TI  - Altered function and surface marker expression of neutrophils induced by rhG-CSF
      treatment in severe congenital neutropenia.
AB  - Neutrophils from patients suffering from severe congenital neutropenia (SCN), who
      were receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF),
      were investigated in order to analyze the previously described decrease in
      chemotaxis. This study demonstrated the decreased chemotaxis to five well-known
      chemoattractants, FMLP, C5a, IL-8, LTB4 and PAF. To further investigate this
      impairment of patients' neutrophils, receptors and receptor turnover for
      chemoattractants were examined using flow cytometry. We found 1) increased FMLP
      receptor and decreased C5a receptor expression, 2) a normal expression of
      intracellular FMLP receptors after incubation with PMA, 3) increased loss and
      decreased re-expression of FMLP receptors after incubation with this peptide, 4)
      normal expression of adhesion glycoproteins CR3 (CD11b/CD18) and LFA1
      (CD11a/CD18), 5) further signs of in vivo preactivation: high expression of Fc
      gamma-RI (CD64) and Fc gamma-RII (CD32), decreased expression of Fc gamma-RIII
      (CD16), increased expression of CD14, and low expression of HLA-DR. These data
      demonstrate that the decrease of chemotaxis of neutrophils from SCN patients is
      not due: a) to a decrease in the number of intra- or extracellular FMLP
      receptors; b) to a decrease of adhesion molecules. However, the decreased
      chemotaxis could result from an altered FMLP receptor turnover. The relevance of
      the altered Fc gamma-receptor pattern for the in vivo occurrence of side-effects,
      e.g. the necrotic vasculitis, of G-CSF treatment is discussed.

PMID- 1370420
TI  - CD1-reactive leukemic cells in bone marrow: presence of Langerhans cell marker on
      leukemic monocytic cells.
AB  - Langerhans cells originate in bone marrow and probably belong to the monocyte
      macrophage lineage. CD1 is a specific marker of Langerhans cells. By
      immunofluorescence and immunoelectron microscopy, CD1a antigen and myeloid
      markers (CD11, CD13, CD14, CD15, CD33, HLA-DR) were studied in 53 cases of acute
      myeloid leukemias (AML) and 3 acute lymphoblastic leukemias (ALL). The 11 ANLL
      without monocytic component were CD1a negative. 2/5 of acute myelomonocytic
      leukemias (AML4) and 9/37 of acute monocytic leukemias (AML5) were positive. All
      3 ALL were negative. No correlation was found between CD1a and myeloid markers.
      CD1a+ AML did not differ from CD1a- AML with regard to cytogenetics or response
      to therapy. The CD1a positive cells may originate from an abnormal proliferation
      of CD1a positive cells which are present in bone marrow and which may
      differentiate into Langerhans cell precursors.

PMID- 1370422
TI  - Evidence for the production of a nonsteroidal endotheliotropic factor by human
      granulosa cells in culture.
AB  - OBJECTIVE: To determine the cellular source of the angiogenic activity displayed
      by follicular fluid (FF). DESIGN: Human granulosa cells were harvested from 27
      follicular aspirates obtained 34 to 36 hours after eight patients, previously
      treated with human menopausal gonadotropin (hMG), follicle-stimulating hormone
      plus hMG, or clomiphene citrate and hMG received human chorionic gonadotropin
      (10,000 IU intramuscularly). Granulosa cells from individual follicles were
      plated at 50,000 cells/cm2 in Medium 199 (Sigma, St. Louis, MO) supplemented with
      either 5% calf serum or 0.1% bovine serum albumin; media collected 24 hours later
      was assayed in vitro measuring endothelial cell migration. Fractions depleted of
      steroids by reversed phase C1 chromatography were assayed as well. RESULTS:
      Granulosa cell-conditioned media from 18 of 27 follicles significantly stimulated
      endothelial cell migration (P less than 0.05). Chemoattractant activity did not
      appear to be related to steroid accumulation in the media and was not diminished
      in steroid depleted fractions. CONCLUSIONS: These findings suggest that human
      granulosa cells are a source of (nonsteroidal) endotheliotropic-angiogenic
      activity in FF.

PMID- 1370421
TI  - 2-Aminopurine inhibits RNA and protein synthesis and reduces catecholamine
      desensitization in C6-2B rat glioma cells.
AB  - We previously proposed that intracellular cyclic AMP accumulation induces a
      putative, rapidly turning over protein inhibitory to further hormone activation
      of adenylate cyclase. In the present study, 2-aminopurine, which has been
      reported to selectively block c-fos gene expression, was used to test the
      hypothesis that c-fos protein might be involved in the desensitization to
      catecholamines was observed in 2-aminopurine-treated C6-2B rat glioma cells.
      However, we found 2-aminopurine to inhibit, in a concentration-dependent manner,
      total cellular RNA and protein synthesis in C6-2B, HeLa, Swiss 3T3 and BALB/c
      cells. mRNA synthesis was also markedly reduced in 2-aminopurine-treated cells.
      These unexpected findings, while supporting our hypothesis of a protein synthesis
      sensitive step in the development of refractoriness, raise concern about the
      specificity of action of 2-aminopurine to inhibit c-fos induction and thus any
      cellular process, including desensitization, which might be regulated by c-fos
      gene expression.

PMID- 1370423
TI  - Perturbation of beta 1 integrin-mediated adhesions results in altered somite cell
      shape and behavior.
AB  - Cell contact and adhesion between somites and the axial extracellular matrix
      (ECM) is likely to play a fundamental role in vertebrate development. In a
      preliminary report we showed that injection of the monoclonal antibody CSAT,
      which recognizes the avian beta 1 integrins, causes a lateral separation of both
      somites and segmental plate tissue from the embryonic axis (Drake and Little,
      1991). In this study we addressed the cell biological response to CSAT injection,
      particularly the cell-ECM interactions involved in maintaining normal somite
      axial relationships. A total of 150 stage 7-10 quail embryos have been injected
      with CSAT and then cultured for varying periods (1-30 hr). CSAT caused somitic
      cells to behave abnormally. Changes include, rounding-up, extensive blebbing, and
      formation of retraction fibers. A majority of separated somites were able to
      assume normal axial position with further time culture. Whether a somite
      subsequently aligned at the axis was dependent on the amount of CSAT injected and
      the postinjection culture period. Embryos in which somites remained separated
      from the axis after relatively long culture intervals (18-24 hr) displayed
      abnormal sclerotomal cell migrations. In no case did control injected embryos
      exhibit cellular alterations. Similarly, the injection of RGD-containing peptides
      had no detectable effect on somitogenesis or somite/segmental plate adhesion to
      the axis. On the basis of these data, we conclude that beta 1 integrins are
      necessary for normal somitic cell adhesions to the axis, but not somite
      segmentation and differentiation.

PMID- 1370424
TI  - Cytotactin is involved in synaptogenesis during regeneration of the frog
      neuromuscular system.
AB  - The expression of cytotactin, an extracellular matrix glycoprotein involved in
      morphogenesis and regeneration, was determined in the normal and regenerating
      neuromuscular system of the frog Rana temporaria. Cytotactin was expressed in
      adult brain and gut as two major components of Mr 190,000 and 200,000 and a minor
      form of higher molecular weight, but was almost undetectable in skeletal muscle
      extract. However, cytotactin was concentrated at the neuromuscular junctions as
      well as at the nodes of Ranvier. After nerve transection, cytotactin staining
      increased in the distal stump along the endoneurial tubes. In preparations of
      basal lamina sheaths of frog cutaneous pectoris muscle obtained by inducing the
      degeneration of both nerve and muscle fibers, cytotactin was found in dense
      accumulations at original synaptic sites. In order to define the role of
      cytotactin in axonal regeneration and muscle reinnervation, the effect of anti
      cytotactin antibodies on the reinnervation of the basal lamina sheaths
      preparations was examined in vivo. In control preparations, regenerating nerve
      terminals preferentially reinnervate the original synaptic sites. In the presence
      of anti-cytotactin antibodies, axon regeneration occurred with normal
      fasciculation and branching but with altered preterminal nerve fibers pathways.
      Ultrastructural observations showed that synaptic basal laminae reinnervation was
      greatly delayed or inhibited. These results suggest that cytotactin plays a
      primordial role in synaptogenesis, at least during nerve regeneration and
      reinnervation in the adult neuromuscular system.

PMID- 1370425
TI  - Prolactin prevents the autoinduction of thyroid hormone receptor mRNAs during
      amphibian metamorphosis.
AB  - We have recently reported that prolactin (PRL) inhibits both morphogenesis and
      cell death in thyroid hormone (T3)-induced amphibian metamorphosis (Tata et al.,
      1991), and that the autoinduction of T3 receptor (TR alpha and beta) mRNA is
      among the most rapid responses of premetamorphic Xenopus tadpoles to T3 (Kawahara
      et al., 1991). We now demonstrate that PRL prevents the rapid T3-induced
      upregulation of TR alpha and beta mRNAs in stages 50-54 Xenopus tadpoles and in
      organ cultures of tadpole tails. This effect is followed by the inhibition of the
      de novo activation of 63-kDa keratin gene by T3. We present an experimentally
      testable model whereby PRL exerts its juvenilizing action by preventing the
      amplification of TR by its autoinduction by T3.

PMID- 1370426
TI  - A 5'-terminal stem-loop structure can stabilize mRNA in Escherichia coli.
AB  - The 5'-untranslated region of the long-lived Escherichia coli ompA transcript
      functions as an mRNA stabilizer capable of prolonging the lifetime in E. coli of
      a number of heterologous messages to which it is fused. To elucidate the
      structural basis of differential mRNA stability in bacteria, the domains of the
      ompA 5'-untranslated region that allow it to protect mRNA from degradation have
      been identified by mutational analysis. The presence of a stem-loop no more than
      2-4 nucleotides from the extreme 5' terminus of this RNA segment is crucial to
      its stabilizing influence, whereas the sequence of the stem-loop is relatively
      unimportant. The potential to form a hairpin very close to the 5' end is a
      feature common to a number of stable prokaryotic messages. Moreover, the lifetime
      of a normally labile message (bla mRNA) can be prolonged in E. coli by adding a
      simple hairpin structure at its 5' terminus. Accelerated degradation of ompA mRNA
      in the absence of a 5'-terminal stem-loop appears to start downstream of the 5'
      end. We propose that E. coli messages beginning with a single-stranded RNA
      segment of significant length are preferentially targeted by a degradative
      ribonuclease that interacts with the mRNA 5' terminus before cleaving internally
      at one or more distal sites.

PMID- 1370427
TI  - Ploidy analysis of epithelial ovarian cancers using image cytometry.
AB  - We used a computerized image analysis system to determine the DNA content of 103
      epithelial ovarian cancers using touch imprints of frozen tumor samples. Similar
      to prior studies of ploidy using flow cytometry, we found that most ovarian
      cancers (78%) were aneuploid while a minority (22%) were diploid. There was no
      relationship between ploidy and stage, histologic grade, or the ability to
      perform optimal cytoreductive surgery. Also, like prior studies using flow
      cytometry, negative second-look laparotomy and survival were somewhat more common
      in advanced-stage patients with diploid cancers than in those with aneuploid
      cancers. We conclude that ploidy of ovarian cancers can be determined using a
      computerized image analysis system to quantitate feulgen staining of cells in
      touch imprints. Ploidy is unlikely to play a role in treatment planning for
      patients with advanced-stage disease. Larger studies of patients with early-stage
      disease are needed, however, to determine whether ploidy is a more accurate means
      of predicting which patients are most likely to benefit from adjuvant therapy.

PMID- 1370428
TI  - Left ventricular insulin-like growth factor I increases in early renal
      hypertension.
AB  - Increasing interest has been directed toward the possible role of trophically
      acting molecules as modulators or initiators, or both, of myocardial hypertrophy.
      The aim of the present study was to investigate the possible role of one such
      molecule, namely, insulin-like growth factor I, in myocardial hypertrophy
      developed in response to renal artery stenosis. Two-kidney, one clip Goldblatt
      hypertension was induced in Wistar rats weighing 180 g, and sham-operated animals
      were used as controls. Blood pressure was increased as early as 2 days after
      clipping (133 +/- 4 versus 116 +/- 4 mm Hg, p less than 0.05), and the increase
      persisted 4 and 7 days after clipping (148 +/- 6 versus 129 +/- 3 mm Hg, p less
      than 0.01 and 171 +/- 5 versus 139 +/- 3 mm Hg, p less than 0.01, respectively).
      Left ventricular weight followed a similar pattern (373 +/- 7 versus 350 +/- 8
      mg, NS, 415 +/- 11 versus 386 +/- 9 mg, p less than 0.01, and 466 +/- 11 versus
      391 +/- 10 mg, p less than 0.01 at 2, 4, and 7 days after clipping,
      respectively), but no changes in body weight between the groups were observed.
      Insulin-like growth factor I messenger RNA (mRNA) was quantified using a solution
      hybridization assay. After 4 days of renal hypertension, there was a significant
      increase in left ventricular insulin-like growth factor I mRNA (2.0 x 10(-18) +/-
      0.48 x 10(-18) versus 0.4 x 10(-18) +/- 0.07 x 10(-18) mol.microgram DNA-1),
      which was no longer detectable 7 days after clipping.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1370429
TI  - Pore-forming ability of major outer membrane proteins from Wolinella recta ATCC
      33238.
AB  - Three major outer membrane proteins with apparent molecular masses of 43, 45, and
      51 kDa were purified from Wolinella recta ATCC 33238, and their pore-forming
      abilities were determined by the black lipid bilayer method. The non-heat
      modifiable 45-kDa protein (Omp 45) showed no pore-forming activity even at high
      KCl concentrations. The single-channel conductances in 1 M KCl of the heat
      modifiable proteins with apparent molecular masses of 43 kDa (Omp 43) and 51 kDa
      (Omp 51) were 0.49 and 0.60 nS, respectively. The proteins formed nonselective
      channels and, as determined by experiments of ion selectivity and zero-current
      potential, were weakly anion selective.

PMID- 1370430
TI  - Characterization of an 18,000-molecular-weight outer membrane protein of
      Haemophilus ducreyi that contains a conserved surface-exposed epitope.
AB  - Identification of antigenically conserved surface components of Haemophilus
      ducreyi may facilitate the development of reagents to diagnose and prevent
      chancroid. A hybridoma derived from a mouse immunized with nontypeable
      Haemophilus influenzae produced a monoclonal antibody (MAb), designated 3B9, that
      bound to 35 of 35 H. ducreyi strains isolated from diverse geographic regions.
      The MAb 3B9 bound to a non-heat-modifiable H. ducreyi outer membrane protein
      (OMP) whose apparent molecular weight was 18,000 (the 18K OMP), and the 3B9
      epitope did not phase vary at a rate of greater than 10(-3) in H. ducreyi. In
      immunoelectron microscopy, the 3B9 epitope was surface exposed, and there was
      intrastrain and interstrain variability in the amount of 3B9 labelling of whole
      cells. The MAb 3B9 cross-reacted with many species of the family Pasteurellaceae
      and bound to the 16.6K peptidoglycan-associated lipoprotein (P6 or PAL) of H.
      influenzae. Unlike P6, the 18K OMP did not copurify with peptidoglycan. In
      Western blots (immunoblots), five of seven serum samples obtained from patients
      with chancroid and four of five serum samples obtained from patients with other
      genital ulcer diseases at the time of presentation contained antibodies that
      bound to the 18K OMP. In a competition enzyme-linked immunosorbent assay, four of
      these serum samples inhibited the binding of 3B9 to H. ducreyi by more than 50%.
      We conclude that members of Pasteurellaceae expressed a conserved epitope on OMPs
      that sometimes had different physical characteristics. Patients with chancroid
      usually have antibodies to the 18K OMP and the 3B9 epitope that may have resulted
      from infection with H. ducreyi or previous exposure to other Haemophilus or
      Actinobacillus sp. strains.

PMID- 1370431
TI  - Myosin-cross-reactive epitope of Shigella flexneri invasion plasmid antigen B.
AB  - IpaB, invasion plasmid antigen B, of Shigella flexneri is a 62-kDa protein
      required for invasion of intestinal epithelial cells. IpaB is also one of several
      major protein antigens recognized by the humoral immune systems of most humans
      and monkeys after infection with shigellae. Computer analysis of the deduced IpaB
      amino acid sequence indicates that an alpha-helical structure is likely through
      much of the molecule. Homology searches with protein data banks show that one
      alpha-helical domain between amino acid residues 95 and 181 has a moderate level
      of identity with myosin and streptococcal M protein. By using a monoclonal
      antibody (2F1) which recognizes an epitope in the amino-terminal third of the
      IpaB protein, it was possible to demonstrate a cross-reactive epitope(s) on
      skeletal muscle myosin. Epitope mapping localized the 2F1 epitope to three
      noncontiguous regions of the IpaB protein within the alpha-helical domain that
      contains homology with myosin. Antibodies produced in rabbits immunized with
      synthetic peptides from one of the 2F1 epitope regions (residues 99 to 110) of
      IpaB were capable of reacting with IpaB as well as myosin. Furthermore, sera from
      several monkeys previously infected with S. flexneri 2a contained antibodies to
      IpaB pep 101-116 (IpaB peptide 101-116) and also myosin. Sera from animals with
      antibodies against other IpaB peptides did not contain antibodies against myosin.

PMID- 1370432
TI  - Helicobacter mustelae isolation from feces of ferrets: evidence to support fecal
      oral transmission of a gastric Helicobacter.
AB  - Helicobacter mustelae has been isolated from stomachs of ferrets with chronic
      gastritis and ulcers. When H. mustelae is inoculated orally into H. mustelae
      negative ferrets, the animals become colonized and develop gastritis, a
      significant immune response, and a transient hypochlorhydria. All of these
      features mimic Helicobacter pylori-induced gastric disease in humans. Because the
      epidemiology of H. pylori infection is poorly understood and its route of
      transmission is unknown, the feces of weanling and adult ferrets were cultured
      for the presence of H. mustelae. H. mustelae was isolated from the feces of 11 of
      36 ferrets by using standard helicobacter isolation techniques. H. mustelae was
      identified by biochemical tests, ultrastructural morphology, reactivity with
      specific DNA probes, and 16S rRNA sequencing. H. mustelae was not recovered from
      20-week-old ferrets which had been H. mustelae positive as weanlings, nor was H.
      mustelae recovered from 1-year-old ferrets. Isolation of H. mustelae from feces
      may correspond to periods of transient hypochlorhydria, or H. mustelae may be
      shed in feces intermittently. The H. mustelae-colonized ferret provides an ideal
      model for studying the pathogenesis and transmission of H. pylori-induced gastric
      disease.

PMID- 1370433
TI  - Genetic control of immune responses in mice to synthetic peptides of a
      Streptococcus mutans surface protein antigen.
AB  - The immune responses to a cell surface protein antigen (PAc) of Streptococcus
      mutans and a peptide corresponding to residues 301 to 319 of the protein antigen
      [PAc(301-319)] in various strains of mice were studied, with attention being
      given to the haplotype of major histocompatibility complex (MHC) class II genes.
      Subcutaneous immunization of mice carrying the MHC class II I-Ad gene [BALB/c,
      B10.D2, B10.GD, and (B10.D2 x B10.G)F1 mice] with the peptide induced strong
      serum immunoglobulin G (IgG) responses to recombinant PAc (rPAc) and the peptide.
      Subcutaneous immunization of mice carrying the haplotype k or b of the H-2 I-A
      gene (C3H/HeN, C57BL/6, B10.BR, B10.A, or B10 mice) with the peptide induced
      intermediate serum IgG responses to rPAc and the peptide, and subcutaneous
      immunization of mice carrying the haplotype s or q of the H-2 I-A gene (DBA/1,
      B10.S, or B10.G mice) induced weak serum IgG responses to rPAc and the peptide
      compared with the responses of mice carrying the I-Ad gene. PAc(301-319) strongly
      induced PAc(301-319)-specific T-cell proliferation in B10.D2 mice but not in
      B10.G mice. The T-cell proliferation in B10.D2 mice was inhibited by treatment of
      antigen-presenting cells with anti-I-Ad monoclonal antibody but not with anti-I
      Ab monoclonal antibody. These results indicate that the immune responses to the
      peptide in mice are genetically restricted or dominated by the MHC class II gene
      (I-Ad). To map antigenic epitopes in PAc(301-319) and PAc in mice bearing
      different H-2 haplotypes, 10 overlapping decapeptides covering PAc(301-319) and
      153 decapeptides covering the entire mature PAc were synthesized. Of 10
      decapeptides covering PAc(301-319), 6, 7, 1, and 1 decapeptides showed strong
      reactions with anti-PAc(301-319) sera from B10.D2 (H-2d), B10.GD (H-2g2), B10.BR
      (H-2k), and B10.A (H-2a) mice, respectively. None of these overlapping
      decapeptides reacted with anti-PAc(301-319) sera from B10.S (H-2s) and B10.G (H
      2q) mice. Epitope-scanning analyses of the mature PAc molecule showed that
      antigenic epitopes scattered throughout the molecule and that antigenic epitope
      patterns differed in mice with different H-2 haplotypes. In addition, there was
      little overlap of immunogenic peptides among the mice with different haplotypes.

PMID- 1370435
TI  - Expression of insulin-like growth factors I and II and their receptor mRNAs in
      primary human astrocytomas and meningiomas; in vivo studies using in situ
      hybridization and immunocytochemistry.
AB  - These studies demonstrate the expression of IGF-1, IGF-11, and their respective
      receptor mRNAs in primary human astrocytomas and meningiomas. In situ
      hybridization and immunocytochemistry have localized a strong expression of both
      IGF-1 and IGF-11 mRNAs and of their protein products in the tumor cells of
      astrocytomas and meningiomas. The expression of IGF-1 and IGF-11 mRNAs in the
      tumor cells was accompanied by the co-expression of their respective type-1 and
      type-11 IGF receptor mRNAs. Control, non-malignant human brain expressed IGF-1
      mRNA and IGF-1 and IGF-11 receptor mRNAs. There was no significant expression of
      IGF-11 MRNA in the control brain specimens. Control pachymeninges (dura mater)
      expressed low levels of IGF-1 mRNA and IGF-1 receptor mRNA. There was no
      significant expression of IGF-11 and IGF-11 receptor mRNAs in pachymeninges. The
      co-expression of IGFs and their receptors in brain tumors may contribute in their
      development and maintenance. The strong inappropriate expression of IGF-11 mRNA
      and its protein product in the tumor cells of astrocytomas and meningiomas, but
      not in normal brain specimens, may serve as molecular markers for the early
      detection of these tumors.

PMID- 1370434
TI  - Residues 20, 22, and 26 determine the subtype specificities of staphylococcal
      enterotoxins C1 and C2.
AB  - Nonconserved residues of staphylococcal enterotoxin C1 (SEC1) were converted to
      their counterparts in SEC2. The mutants that resulted were examined for
      reactivity with monoclonal antibodies (MAbs). Substitution at position 20, 22, or
      26 interfered with binding of an SEC1-specific MAb. SEC1 mutants with
      substitutions at all three positions reacted only with an SEC2-specific MAb.
      Antibody-binding patterns were not associated with isoelectric point differences.
      All mutants retained biological activity.

PMID- 1370437
TI  - The relationship between multi-drug resistance and resistance to natural-killer
      cell and lymphokine-activated killer-cell lysis in human leukemic cell lines.
AB  - Results concerning a possible link between susceptibility to natural-cell
      mediated immune cytolysis and the multi-drug resistance (MDR) phenotype are
      conflicting. We evaluated in human acute lymphocytic leukemia the relationship
      between acquired drug resistance and susceptibility to cytolysis mediated by
      endogenous, interferon-activated, and interleukin-2-activated natural cytotoxic
      cells. Eight human leukemia drug-resistant/sensitive cell line pairs were
      evaluated; drug-resistant sub-lines included those selected for primary
      resistance to adriamycin, etoposide, teniposide, vincristine, and vinblastine. A
      majority of P-glycoprotein-positive MDR sub-lines displayed slight but
      statistically significant resistance to endogenous and/or interferon-activated
      natural-killer(NK)-cell-mediated lysis, as compared with the drug-sensitive
      parental type. P-glycoprotein-negative sub-lines displayed variable NK
      susceptibility; within this group, the variants selected for primary etoposide
      resistance were more susceptible to NK cytolysis than parental cells. Results of
      cold-target-inhibition experiments suggest that altered NK susceptibility does
      not arise solely from modulation of NK target recognition and adherence
      structures. IL2-activated killer (LAK) cells lysed both drug-sensitive and drug
      resistant lines. Two MDR lines selected for primary etoposide resistance
      displayed enhanced LAK susceptibility. In contrast, the 2 variants selected for
      resistance to adriamycin exhibited partial resistance to LAK-mediated killing,
      which could be overcome at high effector-to-target ratios. Our results support
      the development of interleukin-2/LAK immunotherapy for the treatment of leukemias
      with acquired drug resistance.

PMID- 1370436
TI  - Biphasic effect of cAMP-elevating agents on ICAM-1 expression stimulated by
      retinoic acid and interferon gamma.
AB  - Incubation of the human glioma cell line HS 683 in the presence of IFN-gamma or
      retinoic acid strongly stimulates the cell-surface expression of the
      intercellular adhesion molecule ICAM-1. We have investigated the role of the cAMP
      mediated signal transduction pathway in this process and report that
      pharmacological agents which increased the intracellular levels of cAMP exhibited
      a biphasic action on ICAM-1 expression in human glioma cell line HS 683.
      Treatment for 1 hr with 25 microM forskolin or 1 mM isobutylmethylxanthine, or
      for 12 hr with 100 ng/ml pertussis toxin or 50 micrograms/ml cholera toxin
      transiently stimulated ICAM-1 expression with a maximal level of expression 8 hr
      post treatment, after which time ICAM-1 expression returned to the basal level.
      On the other hand, such pretreatments inhibited the inducing effects of either
      retinoic acid or IFN-gamma. Indeed, 24 hr after treatment with cAMP-elevating
      agents, both the retinoic-acid- and the IFN-gamma-induced ICAM-1 expression were
      inhibited by 60 to 80%, with a maximal 90 to 100% inhibition 72 hr post
      treatment. This inhibition of the cell-surface expression of ICAM-1 was confirmed
      at the mRNA level. The intracytoplasmic levels of cAMP were also quantified
      following treatments with forskolin, retinoic acid or IFN-gamma. In response to
      forskolin, cAMP levels increased 30-fold within 5 min, whereas a 10-fold increase
      occurred 60 min following treatment with 10 microM retinoic acid. Interferon
      gamma, in contrast, did not induce cAMP accumulation. These results were also
      correlated with an in vitro activation of adenylyl cyclase activity by retinoic
      acid and inhibition of this activity by IFN-gamma, in a dose-dependent and a GTP
      dependent manner. Our results suggest that the suppression of IFN-gamma-induced
      ICAM-1 expression, obtained upon pre-treatment with cAMP-elevating agents, is due
      to direct antagonism with IFN-gamma action on adenylyl cyclase. However, the
      inhibition of retinoic-acid-induced ICAM-1 expression cannot be explained by the
      same mechanisms. The timing of adenylyl cyclase stimulation and cAMP
      accumulation, as well as the levels of cAMP accumulation, are probably involved
      in this inhibition. Our results also emphasize the fact that the induction of
      ICAM-1 expression is a multi-step process implicating different transductional
      signals among which cAMP might be involved as a second messenger.

PMID- 1370438
TI  - Activation of NK cells in mice following corneal infection with herpes simplex
      virus type-1.
AB  - Natural killer (NK) cells are large granular lymphocytes that mediate antigen
      nonspecific, non-major histocompatibility complex (MHC) restricted lysis of virus
      infected cells. They are thought to play a role in innate resistance to herpes
      simplex virus (HSV) infections. In most animal studies reported to date, the
      virus was injected intraperitoneally, not a natural route of infection. Using a
      murine model of acute HSV-1 ocular infection, we demonstrate that increased
      splenic NK activity is induced in BALB/c mice following corneal infection with
      four different strains of HSV-1. The kinetics of NK cell activation depended on
      the strain of virus and was associated with virulence of the strain and with the
      ability of the viruses to grow in vivo. We also assessed the role of interferon
      alpha/beta, IFN-gamma, and interleukin-2 (IL-2) in the HSV-1 induced NK cell
      activation by treating mice with antisera against these lymphokines prior to
      infection. Treatment with anti-IFN-alpha/beta or anti-IFN-gamma significantly
      reduced NK cell cytotoxicity, suggesting that these lymphokines were involved in
      the activation of NK cells following HSV-1 ocular infection. Treatment with anti
      IL-2 resulted in increased NK cell activity, suggesting that in vivo, IL-2 is
      involved in the suppression of NK cell activity in infected mice. Treatment with
      a combination of anti-IL-2 and anti-IFN also increased NK cytotoxicity. Despite
      the induction of high levels of NK activity, mice developed severe ocular disease
      or died of encephalitis.

PMID- 1370439
TI  - Clonal growth and differentiation of rabbit meibomian gland epithelium in serum
      free culture: differential modulation by EGF and FGF.
AB  - We have established a serum-free clonal culture system to study the growth and
      differentiation of individual progenitor epithelial cells of the meibomian gland
      independent of other cell types and undefined serum factors. Single meibomian
      gland epithelial cells were obtained by subjecting whole meibomian glands to a
      brief EDTA treatment, needle aspiration, and nylon mesh filtration. The cells had
      been isolated by a previously described method using enzymatic and microsurgical
      techniques. Four to five hundred cells obtained were seeded on a 35 mm or 60 mm
      dish with serum-free MCDB 151 medium containing insulin, transferrin, selenium,
      ethanolamine, o-phosphorylethanolamine, dimethyl sulfoxide, and calcium. Control
      cultures with this basic medium did not show continuous clonal growth. Addition
      of epidermal growth factor (EGF) from 1 to 5 and 10 ng/ml enhanced clonal growth
      with a decreasing effect as measured by colony forming efficacy and colony size.
      Clonal growth was associated with the occurrence of two types of colony
      morphology and an increase in intracellular lipid production in the BrdU-labelled
      cells, shown by Nile red fluorescent staining. In contrast, the clonal growth
      stimulated by addition of acidic fibroblast growth factor (aFGF) from 1 to 100
      ng/ml exhibited a pattern of an initial increase followed by a decrease, with the
      maximum noted at 10 ng/ml. Moreover, the aFGF-stimulated clonal growth was
      associated with a uniform colony morphology and minimal lipid synthesis even in
      the non-BrdU-labelled cells. These results indicate that clonal growth of
      meibomian gland epithelium can be achieved in a serum-free culture by adding
      either of these two peptide growth factors. Furthermore, the clonal growth
      stimulated by EGF was associated with progressive cellular differentiation more
      so than that of aFGF. Further exploration of such a differential regulation of
      proliferation and differentiation by EGF and aFGF may provide a better
      understanding of normal meibomian gland function and pathogenesis of various
      meibomian gland disorders.

PMID- 1370440
TI  - Characteristics of a glycoprotein in the ocular surface glycocalyx.
AB  - A monoclonal antibody has been produced that binds to the apical squames
      (flattened cells) of the rat ocular surface epithelium and to the goblet cells of
      the conjunctiva. Immunoelectron microscopic localization of the antigen indicates
      that in apical cells it is present along the apical-microplical membrane in the
      region of the glycocalyx. In subapical squames, the antigen is in cytoplasmic
      vesicles. In some goblet cells, the antigen is in the Golgi network, and in
      others, it is located primarily in the membrane of the mucous granules. SDS-PAGE
      and immunoblot analysis demonstrate that the molecular weight of the antigen is
      greater than 205 kD, and the electrophoretic band stains with Alcian blue
      followed by silver stain. Periodate oxidation of immunoblots and cryostat
      sections removes antibody binding. Neuraminidase treatment of cryostat sections
      does not remove antibody binding, whereas N-glycanase does. Taken together, these
      data indicate that the antigen recognized by the monoclonal antibody is a
      carbohydrate epitope on a high-molecular-weight, highly glycosylated glycoprotein
      in the glycocalyx of the ocular surface epithelium and goblet cell mucin granule
      membrane. The antigen appears to be stored within cytoplasmic vesicles and
      reaches the glycocalyx when cells differentiate to the apical-most position where
      the glycocalyx interfaces with the mucin layer of the tear film.

PMID- 1370442
TI  - Hoechst 33342 for microfluorimetric measurement of adrenocortical tumor cell
      proliferation.

PMID- 1370441
TI  - Retinal pigment epithelial cells secrete interleukin-6 in response to interleukin
      1.
AB  - Interleukin-6 (IL-6) is a peptide whose properties include the ability to
      activate T-lymphocytes, stimulate the secretion of immunoglobulin, induce
      neuronal differentiation, and trigger the release of acute phase proteins. We
      have detected IL-6-like activity in conditioned medium from cultured human
      retinal pigment epithelial (RPE) cells with a bioassay based on the ability of IL
      6 to induce the proliferation of murine B-9 plasmacytoma cells. Biologic activity
      increased approximately 90-fold when the cells were cultured in the presence of
      IL-1 alpha (30 units/ml). Western blot analysis confirmed that conditioned medium
      from IL-1 alpha-stimulated RPE cells contained peptides with molecular weights
      ranging between 19,000 and 30,000 and reactive with antibody to IL-6. Finally,
      Northern blot analysis indicated that cells cultured in the presence of
      interleukin-1 contained a 1.2 kilobase transcript that hybridized to a cDNA probe
      specific for IL-6 messenger RNA. IL-6 peptide on Western blots and mRNA on
      Northern blots were undetectable unless cells were cultured in the presence of IL
      1 alpha. Although IL-6 is synthesized by a variety of cell types, this report is
      the first to detect its synthesis by an eye-specific cell type. Furthermore,
      these observations indicate that retinal pigment epithelial cells respond to IL
      1, a cytokine that previously has been implicated in ocular inflammation.

PMID- 1370443
TI  - Expression of fibroblast growth factor receptors by embryonal carcinoma cells and
      early mouse embryos.
AB  - We have previously shown that differentiation of embryonal carcinoma (EC) cells
      leads to both increased binding of FGF (fibroblast growth factor) and suppression
      of k-FGF expression. In the current study, we examined the expression of FGF
      receptors by EC cells, EC-derived differentiated cells and early mammalian
      embryos using the technique of reverse transcription-polymerase chain reaction
      (RT-PCR). We determined that both mouse, F9, and human, NT2/D1, EC cells as well
      as their differentiated counterparts express transcripts for two forms of FGF
      receptors, bek (bacterially expressed kinase) and flg (fms-like gene). In
      addition, we determined that mouse blastocysts express flg transcripts. The
      presence of FGF receptor transcripts in early embryos and the previous finding of
      FGF-related activity in medium conditioned by mouse blastocysts argue that the
      FGF family plays important roles during early mammalian development.

PMID- 1370444
TI  - Thyroid hormone up-regulates NGFI-A gene expression in rat brain during
      development.
AB  - NGFI-A is an immediate-early response gene induced by signals that initiate
      growth and differentiation. Its mRNA encodes a sequence-specific transcriptional
      activator possibly implicated in the control of brain developmental processes.
      Due to the essential role of thyroid hormone for a correct brain development, we
      have now investigated the possible regulation by 3,5,3'-triiodo-L-thyronine (T3)
      of NGFI-A gene expression during maturation of the central nervous system. Our
      results indicate that expression of mRNA encoding NGFI-A transcription factor is
      about 8-fold decreased in the brain of neonatal hypothyroid rats. No changes were
      seen when hypothyroidism was induced in adult life. T3 treatment increased NGFI-A
      mRNA within 1 h, suggesting that thyroid hormone effect is likely to be a direct
      one. These data indicate a strong regulation by thyroid hormone of the expression
      of the growth factor inducible gene NGFI-A during brain development, making this
      gene a suitable model to study T3 action in the early developing nervous system.

PMID- 1370445
TI  - The binding of a novel bisheteroarylpiperazine mediates inhibition of human
      immunodeficiency virus type 1 reverse transcriptase.
AB  - The bisheteroarylpiperazines (BHAPs) are potent inhibitors of human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and specifically
      block HIV-1 replication (Romero, D. L., Busso, M., Tan, C.-K., Reusser, F.,
      Palmer, J. R., Poppe, S. M., Aristoff, P. A., Downey, K. M., So, A. G., Resnick,
      L., and Tarpley, W. G. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 8806-8810). Here
      we show that the radiolabeled BHAP [3H]U-88204 binds specifically to HIV-1 RT
      with high affinity (KD of 50 nM) and a stoichiometry of 1 mol of U-88204 per 1
      mol of p66/p51 RT heterodimer. Binding of [3H]U-88204 to RT is unaffected by the
      presence of saturating poly(rC).oligo (dG)12-18 template-primer. Direct
      measurement of competition between [3H]U-88204 and other RT inhibitors for
      binding to RT reveals mutually exclusive competition between [3H]U-88204 and the
      non-nucleoside RT inhibitor BI-RG-587 (Kopp, E. B., Miglietta, J. J.,
      Shrutkowski, A. G., Shih, C.-K., Grob, P. M. and Skoog, M.T. (1991) Nucleic Acids
      Res. 19, 3035-3039), indicating that both share the same binding site.
      Phosphonoformate in concentrations up to 50 microM shows no competition with
      [3H]U-88204 for binding to RT either alone or in the presence of template-primer.
      Dideoxynucleotide RT inhibitors affect the binding of [3H]U-88204 to RT when
      complementary template-primer is present. [3H]U-88204 and the dideoxynucleotide
      ddGTP can bind RT simultaneously, but the presence of one ligand decreases the
      affinity of RT for the second. Inasmuch as ddGTP approximates the nucleotide
      substrate of RT, the direct demonstration of an RT-dideoxynucleotide-[3H]U-88204
      complex validates the use of indirect kinetic methods to assess the strength of
      BHAP interaction with RT and suggests that RT inhibition by U-88204 is achieved
      via effects on nucleotide substrate binding.

PMID- 1370446
TI  - cDNA to chick lumican (corneal keratan sulfate proteoglycan) reveals homology to
      the small interstitial proteoglycan gene family and expression in muscle and
      intestine.
AB  - A 1.9-kb cDNA clone to chick lumican (keratan sulfate proteoglycan) was isolated
      by screening an expressing vector library made from chick corneal RNA with
      antiserum to chick corneal lumican. The cDNA clone contained an open reading
      frame coding for a 343-amino acid protein, Mr = 38,640. Structural features of
      the deduced sequence include: a 18-amino acid signal peptide, cysteine residues
      at the N- and C-terminal regions, and a central leucine-rich region (comprising
      62% of the protein) containing nine repeats of the sequence LXXLXLXXNXL/I, where
      X represents any amino acid. Lumican contains three variations of this sequence
      that are tandemly linked to form a unit and three units tandemly linked to form
      the leucine-rich region. The sequential arrangement of these repeats and their
      spacing suggest that this region arose by duplication. The deduced sequence shows
      five potential N-linked glycosylation sites, four of which are in the leucine
      rich region. These sites are also potential keratan sulfate attachment sites. The
      cDNA clone to lumican hybridizes to a 2.0-kb mRNA found in tissues other than
      cornea, predominantly muscle and intestine. Radiolabeling and immunoprecipitation
      studies show that lumican core protein is also synthesized by these tissues. The
      primary structure of lumican is similar to fibromodulin, decorin, and biglycan,
      which indicates it belongs to the small interstitial proteoglycan gene family.
      The expression of lumican in tissues other than cornea indicates a broader role
      for lumican besides contributing to corneal transparency.

PMID- 1370447
TI  - The role of the matrix calcium level in the enhancement of mitochondrial pyruvate
      carboxylation by glucagon pretreatment.
AB  - The effect of Ca2+ on the rate of pyruvate carboxylation was studied in liver
      mitochondria from control and glucagon-treated rats, prepared under conditions
      that maintain low Ca2+ levels (1-3 nmol/mg of protein). When the matrix-free
      [Ca2+] was low (less than 100 nM), the rate of pyruvate carboxylation was not
      significantly different in mitochondria from control and glucagon-treated rats.
      Accumulation of 5-8 nmol of Ca2+/mg, which increased the matrix [Ca2+] to 2-5
      microM in both preparations, significantly enhanced pyruvate carboxylase flux by
      20-30% in the mitochondria from glucagon-treated rats, but had little effect in
      control preparations. Higher levels of Ca2+ (up to 75 nmol/mg) inhibited pyruvate
      carboxylation in both preparations, but the difference between the mitochondria
      from control and glucagon-treated animals was maintained. The enhancement of
      pyruvate dehydrogenase flux by mitochondrial Ca2+ uptake was also significantly
      greater in mitochondria from glucagon-treated rats. These differential effects of
      Ca2+ uptake on enzyme fluxes did not correlate with changes in the mitochondrial
      ATP/ADP ratio, the pyrophosphate level, or the matrix volume. Arsenite completely
      prevented 14CO2 incorporation when pyruvate was the only substrate, but caused
      only partial inhibition when succinate and acetyl carnitine were present as
      alternative sources of energy and acetyl-CoA. Under these conditions,
      mitochondria from glucagon-treated rats were less sensitive to arsenite than the
      control preparations, even at low Ca2+ levels. We conclude that the Ca(2+)
      dependent enhancement of pyruvate carboxylation in mitochondria from glucagon
      treated rats is a secondary consequence of pyruvate dehydrogenase activation;
      glucagon treatment is suggested to affect the conditions in the mitochondria that
      change the sensitivity of the pyruvate dehydrogenase complex to dephosphorylation
      by the Ca(2+)-sensitive pyruvate dehydrogenase phosphatase.

PMID- 1370448
TI  - Nuclear signaling in human neutrophils. Stimulation of RNA synthesis is a
      response to a limited number of proinflammatory agonists.
AB  - At inflammatory sites, neutrophils are stimulated by a range of proinflammatory
      molecules which elicit a number of cellular responses. Considerable information
      on the cytoplasmic events that occur following activation of neutrophils at the
      cell membrane level already exists. In this study, we have focused on the ability
      of neutrophil agonists to initiate nuclear signaling events by investigating the
      induction of de novo RNA synthesis. Of a total of 14 different known potent
      leukocyte agonists, only three had a significant effect on the induction of RNA
      synthesis in neutrophils; the formylated oligopeptide formyl-methionyl
      leucylphenylalanine (fMet-Leu-Phe), granulocyte-macrophage colony-stimulating
      factor, and tumor necrosis factor alpha. All three agonists induced de novo RNA
      synthesis in neutrophils at concentrations known to be optimal for the activation
      of a number of other cellular responses occurring in inflammation. Of
      significance was the observation that activation of RNA synthesis in neutrophils
      is a G-protein-mediated event, is also dependent on tyrosine phosphorylation, but
      is not influenced by cAMP. Finally, we have demonstrated that all three agonists
      also induce de novo synthesis of a limited number of proteins, with granulocyte
      macrophage colony-stimulating factor and fMet-Leu-Phe having the most potent
      effect. These studies define the effects of neutrophil agonists on de novo RNA
      and protein synthesis in a proinflammatory context and suggest that these events
      in neutrophils occur in a restricted fashion, highly dependent on the stimuli
      present at sites of inflammation.

PMID- 1370449
TI  - Structural analysis of low TCR-CD3 complex expression in T cells of an
      immunodeficient patient.
AB  - Normal membrane expression of the T cell receptor (TCR) depends on the
      coordinated synthesis and assembly of all seven proteins composing the complex,
      i.e. the TCR alpha and beta chains, the CD3 gamma, delta, and epsilon chains, and
      the zeta-zeta or zeta-eta dimer. In an experimental TCR membrane-defective T cell
      variant (Sussman, J. L., Bonifacino, J. S., Lippincott-Schwartz, J., Weissman, A.
      M., Saito, T., Klausner, R. D., and Ashwell, J. D. (1988) Cell 52, 85-95) and in
      two siblings whose lymphocytes express only a low level of the TCR/CD3 complex
      (Alarcon, B., Berkhout, B., Breitmeyer, J., and Terhorst, C. (1988) N. Engl. J.
      Med. 319, 1203-1208), a defect in zeta chain synthesis and/or assembly was
      thought to account for the defective membrane synthesis of the whole complex. We
      report on another immunodeficient patient whose T lymphocytes express the T cell
      receptor at one-tenth of normal fluorescence intensity and are not triggered to
      proliferate in vitro by anti-CD3 or anti-CD2 antibodies. Biochemical analysis of
      the patient's surface-iodinated peripheral blood lymphocytes failed to detect TCR
      alpha and beta, or CD3 gamma, delta, and epsilon proteins but revealed the
      presence of the zeta homodimer (probably as a result of the high proportion of
      natural killer cells). In the cytoplasm, TCR alpha and beta proteins and the zeta
      chain were detected, but, using monoclonal anti-CD3 antibodies, the CD3 gamma,
      delta, and epsilon chains were not. In addition, the CD3 epsilon chain was not
      detected with polyclonal antiserum in a very sensitive Western blotting detection
      system. The zeta chain was shown to be synthesized by the patient's T and natural
      killer cells. Northern blot analysis revealed normal levels of normal-size TCR
      beta and CD3 gamma, delta gene-specific mRNAs and decreased levels of TCR alpha
      mARN; CD3 epsilon gene transcripts were of abnormal size and present in lower
      than normal amounts. These findings suggest that this defect in T cell receptor
      CD3 expression involves a mutation in the CD3 epsilon gene leading to the
      synthesis of an abnormal and unstable CD3 epsilon subunit.

PMID- 1370450
TI  - Hydrofluoric acid-treated tau PHF proteins display the same biochemical
      properties as normal tau.
AB  - Tau (tau) is a major constituent of paired helical filaments (PHF) found in
      Alzheimer's disease. The current study examines the possibility that the distinct
      properties of PHF-associated tau proteins (tau PHF) result from post
      translational modifications of normal soluble tau (tau s). Following hydrofluoric
      acid (HF) treatment, tau PHF proteins are heat- and acid-stable, soluble in 2-(N
      morpholino)ethanesulfonic acid buffers and display the same molecular weight, pI,
      and immunochemical properties as normal tau s. Alkaline phosphatase treatment of
      dissociated PHF results in similar, although less extensive, electrophoretic
      changes and a reduction in PHF-1 immunoreactivity. Therefore, phosphorylation of
      normal tau s appears to be responsible for the distinct properties of tau PHF.
      Although our results suggest that all of the normal tau isoforms are in PHF, the
      relative abundance of individual tau species differs in HF-treated PHF and tau s
      samples. Moreover, the loss of PHF following HF treatment suggests that post
      translational modifications contribute to the structural stability of PHF.

PMID- 1370451
TI  - Structural determinants for binary and ternary complex formation between insulin
      like growth factor-I (IGF-I) and IGF binding protein-3.
AB  - Structural analogs of recombinant human insulin-like growth factor-I (IGF-I),
      with alterations to each of the B, C, A, and D domains, have been tested for
      their ability to form binary complexes with IGF-binding protein-3 (IGFBP-3) and
      ternary complexes with IGFBP-3 and the acid-labile subunit (alpha-subunit). Two
      functionally distinct regions of IGF-I have been identified. The first, involving
      residues 3 and 4 and the alpha-helix between residues 8 and 18 of the B-domain,
      as well as residues 49-51 in the A-domain, appears important for IGFBP-3 binding,
      such that substitution of these residues results in decreased binary complex
      available for alpha-subunit binding. The second region, distal to the IGFBP-3
      binding epitope and primarily involving the D-domain and B-domain near residue
      24, with some involvement of the C-domain, appears slightly inhibitory to binary
      complex formation, such that analogs with a truncated D-domain or with a Gly4
      bridge substituted for the C-domain show enhanced binding to IGFBP-3. However,
      binary complexes formed from these analogs bind the alpha-subunit with reduced
      affinity, the effect being most marked when substitution of the C-domain, or
      replacement of Tyr24, is superimposed on D-domain truncation. It is concluded
      that although the alpha-subunit does not itself bind IGF-I, its interaction with
      IGFBP-3 in the ternary complex is dependent on structural determinants on IGF-I
      distal to the IGFBP-3 binding domain.

PMID- 1370452
TI  - Antibodies against synthetic peptides used to determine the topology and site of
      glycosylation of the cGMP-gated channel from bovine rod photoreceptors.
AB  - Peptides corresponding to amino acids 321-339 (peptide GS21) and 416-431 (peptide
      GS31) of the cGMP-gated channel from bovine rod photoreceptors were synthesized
      and used as antigens for the preparation of polyclonal antibodies. After affinity
      purification, both antipeptide antibodies were found to bind specifically to the
      channel protein after Western blotting, but only the antibody against GS21 gave
      satisfactory results on enzyme-linked immunosorbent assay and electron
      microscopy. Using immunocytochemistry, we were able to localize amino acids 321
      339 to the extracellular side of the rod photoreceptor plasma membrane. By
      synthesizing heptapeptides corresponding to amino acids 324-330 (peptide GS2s)
      and 420-426 (peptide GS3s), we were able to affinity purify antibodies specific
      for two N-glycosylation consensus sites in the channel protein. As assessed by
      Western blotting, antibodies against GS3s were found to bind to both the
      glycosylated and deglycosylated channel proteins, whereas antibodies against GS2s
      only bound to the channel protein after enzymatic deglycosylation. Together,
      these results allow the refinement of folding models for the cGMP-gated channel
      and implicate Asn-327 as being the sole site of N-glycosylation.

PMID- 1370453
TI  - Cloning of a Na(+)- and Cl(-)-dependent betaine transporter that is regulated by
      hypertonicity.
AB  - Many hypertonic bacteria, plants, marine animals, and the mammalian renal medulla
      are protected from the deleterious effects of high intracellular concentrations
      of electrolytes by accumulating high concentrations of the nonperturbing osmolyte
      betaine. When kidney-derived Madin-Darby canine kidney (MDCK) cells are cultured
      in hypertonic medium, they accumulate betaine to 1,000 times its medium
      concentration. This results from induction by hypertonicity of high rates of
      betaine transport into cells. We have isolated a cDNA (BGT-1) encoding a renal
      betaine transporter by screening an MDCK cell cDNA library for expression of a
      betaine transporter in Xenopus oocytes. The cDNA encodes a single protein of 614
      amino acids, with an estimated molecular weight of 69 kDa. The deduced amino acid
      sequence exhibits highly significant sequence and topographic similarity to brain
      gamma-amino-n-butyric acid (GABA) and noradrenaline transporters, suggesting that
      the renal BGT-1 is a member of the brain GABA/noradrenaline transporter gene
      family. Expression in oocytes indicates that the BGT-1 protein has both betaine
      and GABA transport activities that are Cl(-)- as well as Na(+)-dependent and
      functionally similar to betaine and GABA transport in MDCK cells. Northern
      hybridization indicates that transporter mRNA is localized to the kidney medulla
      and is induced in MDCK cells by hypertonicity.

PMID- 1370454
TI  - The delta'-subunit of higher plant six-subunit mitochondrial F1-ATPase is
      homologous to the delta-subunit of animal mitochondrial F1-ATPase.
AB  - Mitochondrial F1-ATPases purified from several dicotyledonous plants contain six
      different subunits of alpha, beta, gamma, delta, delta' and epsilon. Previous N
      terminal amino acid sequence analyses indicated that the gamma-, delta-, and
      epsilon-subunits of the sweet potato mitochondrial F1 correspond to the gamma
      subunit, the oligomycin sensitivity-conferring protein and the epsilon-subunit of
      animal mitochondrial F1F0 complex (Kimura, T., Nakamura, K., Kajiura, H.,
      Hattori, H., Nelson, N., and Asahi, T. (1989) J. Biol. Chem. 264, 3183-3186).
      However, the N-terminal amino acid sequence of the delta'-subunit did not show
      any obvious homologies with known protein sequences. A cDNA clone for the delta'
      subunit of the sweet potato mitochondrial F1 was identified by oligonucleotide
      hybridization selection of a cDNA library. The 1.0-kilobase-long cDNA contained a
      600-base pair open reading frame coding for a precursor for the delta'-subunit.
      The precursor for the delta'-subunit contained N-terminal presequence of 21-amino
      acid residues. The mature delta'-subunit is composed of 179 amino acids and its
      sequence showed similarities of about 31-36% amino acid positional identity with
      the delta-subunit of animal and fungal mitochondrial F1 and about 18-25% with the
      epsilon-subunit of bacterial F1 and chloroplast CF1. The sweet potato delta'
      subunit contains N-terminal sequence of about 45-amino acid residues that is
      absent in other related subunits. It is concluded that the six-subunit plant
      mitochondrial F1 contains the subunit that is homologous to the oligomycin
      sensitivity-conferring protein as one of the component in addition to five
      subunits that are homologous to subunits of animal mitochondrial F1.

PMID- 1370455
TI  - Cloning, functional expression, and developmental regulation of a neuropeptide Y
      receptor from Drosophila melanogaster.
AB  - Neuropeptide Y, peptide YY, and pancreatic polypeptide are homologous 36-amino
      acid peptides that differ from most other peptide transmitters by having a
      relatively rigid conformation in aqueous solutions, defined as the pancreatic
      polypeptide fold, and a critical C-terminal tyrosine amide. These peptides serve
      as gastrointestinal hormones and neurotransmitters. A cDNA encoding a novel G
      protein-coupled receptor activated by neuropeptide Y was cloned from Drosophila
      by use of degenerate oligonucleotide primers and polymerase chain reaction
      amplification of cDNA prepared from transcripts expressed early in embryogenesis.
      The cDNA encodes a protein of 449 amino acids with the characteristics of a G
      protein-coupled receptor and shares significant amino acid identity with
      mammalian tachykinin receptors. When expressed in Xenopus oocytes, the PR4
      protein is activated by mammalian neuropeptides in the order: peptide YY greater
      than neuropeptide Y much greater than pancreatic polypeptide. Northern analysis
      showed that PR4 receptor is expressed at equivalent levels in adult Drosophila
      head and body and that the expression of the PR4 receptor is regulated during
      development. The molecular characterization of this receptor should lead to a
      better understanding of the functional role of this important family of hormone
      receptors in adult organisms and during development.

PMID- 1370456
TI  - Identification and characterization of the enzymatic activity of zeta-crystallin
      from guinea pig lens. A novel NADPH:quinone oxidoreductase.
AB  - zeta-Crystallin is a major protein in the lens of certain mammals. In guinea pigs
      it comprises 10% of the total lens protein, and it has been shown that a mutation
      in the zeta-crystallin gene is associated with autosomal dominant congenital
      cataract. As with several other lens crystallins of limited phylogenetic
      distribution, zeta-crystallin has been characterized as an "enzyme/crystallin"
      based on its ability to reduce catalytically the electron acceptor 2,6
      dichlorophenolindophenol. We report here that certain naturally occurring
      quinones are good substrates for the enzymatic activity of zeta-crystallin. Among
      the various quinones tested, the orthoquinones 1,2-naphthoquinone and 9,10
      phenanthrenequinone were the best substrates whereas menadione, ubiquinone, 9,10
      anthraquinone, vitamins K1 and K2 were inactive as substrates. This quinone
      reductase activity was NADPH specific and exhibited typical Michaelis-Menten
      kinetics. Activity was sensitive to heat and sulfhydryl reagents but was very
      stable on freezing. Dicumarol (Ki = 1.3 x 10(-5) M) and nitrofurantoin (Ki = 1.4
      x 10(-5) M) inhibited the activity competitively with respect to the electron
      acceptor, quinone. NADPH protected the enzyme against inactivation caused by
      heat, N-ethylmaleimide, or H2O2. Electron paramagnetic resonance spectroscopy of
      the reaction products showed formation of a semiquinone radical. The enzyme
      activity was associated with O2 consumption, generation of O2- and H2O2, and
      reduction of ferricytochrome c. These properties indicate that the enzyme acts
      through a one-electron transfer process. The substrate specificity, reaction
      characteristics, and physicochemical properties of zeta-crystallin demonstrate
      that it is an active NADPH:quinone oxidoreductase distinct from quinone
      reductases described previously.

PMID- 1370457
TI  - Secondary structure of the mRNA for ribosomal protein S20. Implications for
      cleavage by ribonuclease E.
AB  - A synthetic RNA transcript containing the entire sequence of one of the two
      natural mRNAs for Escherichia coli ribosomal protein S20 is a substrate for
      specific cleavage by an endonuclease which is or depends on ribonuclease E
      (Mackie, G. A. (1991) J. Bacteriol. 173, 2488-2497). Partial cleavage with
      ribonucleases T1 or CL3 and limited modification with dimethyl sulfate have been
      employed to identify residues that are likely to be single stranded in the S20
      mRNA's native state. The data show that the 5' one-third of the mRNA is
      relatively unstructured whereas the 3' one-third is extensively folded. The
      latter property can account for the previously observed accumulation of a 147
      residue product co-terminal with the 3' end of the S20 mRNA (Mackie, G. A. (1989)
      J. Bacteriol. 171, 4112-4120). Sites of cleavage by the ribonuclease E-dependent
      activity map to single-stranded regions of the RNA. In addition, denaturation of
      the RNA substrate results in loss of susceptibility to the ribonuclease E
      dependent activity and simultaneous loss of the single-stranded character of the
      two most prominent cleavage sites. It is proposed that ribonuclease E is a single
      strand-specific enzyme with few primary structural constraints but a preference
      for an AU dinucleotide 3' to the site of cleavage.

PMID- 1370458
TI  - Molecular cloning and characterization of v-mos-activated transformation
      associated proteins.
AB  - Using monoclonal antibodies we previously detected two forms of transformation
      associated proteins, a 64-kDa protein and a 68-kDa protein, in temperature
      sensitive 110-Moloney murine sarcoma virus-mutant-transformed rat kidney 6m2
      cells. The identity and functions of the transformation-associated proteins were
      previously unknown. By molecular cloning techniques and immunoscreening, we have
      isolated two cDNA clones (34A and 79B3) that were found by Western blot analysis
      to code for a monoclonal anti-transformation-associated protein antibody-reactive
      polypeptide of approximately 58 kDa. Limited restriction enzyme mapping indicated
      34A and 79B3 are two different cDNA clones. The nucleotide sequence of 34A cDNA
      was determined, and a search of GenBank revealed that it is identical to that of
      rat transin-2. The deduced amino acid sequence of 34A shares 71% sequence
      identity with rat transin and 41-76% identity with six human metalloproteinases.
      The limited restriction enzyme mapping and partial nucleotide sequencing data
      indicated that 79B3 may be the rat transin gene. When either 34A cDNA or 79B3
      cDNA was used as a probe in Northern blot analysis, one mRNA band of
      approximately 1.9 kilobases was detected in 6m2 cells grown at the permissive
      temperature of 33 degrees C, at which the cells exhibited transformation
      properties, and a much lower level in 6m2 cells grown at the nonpermissive
      temperature of 39 degrees C, at which the cells reverted to normal phenotypes.
      These results suggest that at 39 degrees C, these two genes were not transcribed
      at the same level as at 33 degrees C. Zymogram and Western blot analysis of 6m2
      cells further confirmed that the 64- and 68-kDa proteins have metalloproteinase
      activities and that the synthesis of metalloproteinases was also temperature
      sensitive. Apparently, the two proteins we formerly designated transformation
      associated proteins are members of the rat transin gene family. Therefore, within
      v-mos transformed 6m2 cells, the absence of transformation-associated protein
      (metalloproteinase) synthesis at the nonpermissive temperature was due to the
      absence of transcription of two rat transin genes.

PMID- 1370459
TI  - The mouse gastric H,K-ATPase beta subunit. Gene structure and co-ordinate
      expression with the alpha subunit during ontogeny.
AB  - The gastric H,K-ATPase (EC 3.6.1.3) is responsible for acid secretion into the
      stomach and is composed of two subunits, alpha and beta. The structure of the
      gene encoding the mouse beta subunit and the expression of both subunits during
      ontogeny are reported. The gene spans approximately 12 kilobase pairs and
      contains 7 exons. The positions at which introns interrupt the coding regions of
      the mouse H,K-ATPase beta subunit and mouse Na,K-ATPase (EC 3.6.1.37) beta 2
      subunit genes are identical. The alternative beta subunit isoform of the Na,K
      ATPase, beta 1, has a similar but not identical gene structure. Primer extension
      and S1 nuclease analysis of RNA isolated from mouse stomachs aged between 2 and
      25 days indicated that major transcription-initiation sites are between 22 and 25
      base pairs 5' of the translation initiation site at all ages. The expression of
      the H,K-ATPase alpha and beta subunit genes during ontogeny (day 1-40) was found
      to be co-ordinated. Protein levels of both the ATPase alpha and beta subunits
      were very low until day 15 and then increased to adult levels by day 30. In any
      mucosal cell throughout ontogeny, expression of the beta subunit gene invariably
      coincided with the expression of the alpha subunit gene. Cells detected by anti
      H,K-ATPase beta subunit antibodies in sections from 10- and 30-day-old mice all
      had typical morphology of parietal cells and were arranged in glandular
      structures. Co-ordinate expression of the two subunit genes suggest that the
      regulatory mechanisms will be similar and that the beta subunit may be required
      for localization and function of the catalytic alpha subunit.

PMID- 1370460
TI  - Effect of glycoinositolphospholipid anchor lipid groups on functional properties
      of decay-accelerating factor protein in cells.
AB  - The inositol ring in the glycoinositolphospholipid (GPI) anchor of human decay
      accelerating factor (DAF) is unmodified in nucleated cells, whereas it is fatty
      acid acylated in erythrocytes (Ehu). To assess the effect of this and of the
      glycerol sn-2-associated acyl substituent on the abilities of DAF to cell
      membrane incorporate and function, 1) endogenous (physiologically anchored) DAF
      proteins bearing three- and two-"footed" GPI anchors were purified from Ehu and
      HeLa cells and 2) synthetic DAF variants bearing alternative one- "footed"
      anchors (retaining either the sn-1 glycerol- or inositol-associated lipid) were
      prepared by alkaline hydroxylamine treatment and phosphatidylinositol-specific
      phospholipase D digestion of Ehu DAF, respectively. The different DAF species
      were added to antibody-sensitized sheep erythrocytes (EshA) and their abilities
      to insert into the plasma membranes of the cells and control subsequent
      complement activation on their surfaces were compared. DAF proteins bearing all
      four GPI anchor structures adhered to the Esh hemolytic intermediates and
      inhibited expression of C3 convertase (C4b2a) activity. However, mixing of DAF
      treated EshA with untreated EshAC142 and stripping of cell-associated DAF
      proteins with vesicles showed that only the physiologically anchored proteins
      remained stably associated with the lipid bilayer and functioned intrinsically.
      Both three- and two-"footed" Ehu and HeLa DAF proteins exhibited comparable
      ability to incorporate and function in the intermediates as well as to accumulate
      to levels 1000-fold higher/cell in Schistosoma mansoni schistosomula. These
      findings indicate that 1) an intact inositolphospholipid-containing GPI anchor is
      necessary for stable membrane integration and intrinsic function, 2) endogenous
      GPI anchors (with either unsubstituted and acylated inositol) incorporate and
      function with comparable efficiency, and 3) the transfer of either endogenous DAF
      form can account for the previously described circumvented uptake of human C3b by
      blood stage schistosomula.

PMID- 1370461
TI  - The alpha 4(IV) chain of basement membrane collagen. Isolation of cDNAs encoding
      bovine alpha 4(IV) and comparison with other type IV collagens.
AB  - Renal basement membranes are believed to contain five distinct type IV collagens.
      An understanding of the specific roles of these collagens and the specificities
      of their interactions will be aided by knowledge of their comparative structures.
      Genes for alpha 1(IV), alpha 2(IV), alpha 3(IV), and alpha 5(IV) have been cloned
      and the deduced peptide sequences compared. A fifth chain, alpha 4(IV), has been
      identified in glomerular and other basement membranes. Using a polymerase chain
      reaction-based strategy and short known peptide sequences from the noncollagenous
      domain (NC1), we have cloned and characterized partial bovine cDNAs of alpha
      4(IV). Sequence analysis shows that this molecule has characteristic features of
      type IV collagens including an NH2-terminal Gly-X-Y domain which is interrupted
      at several points and a COOH-terminal NC1 domain with 12 cysteine residues in
      positions identical to those of other type IV collagens. Within the NC1 domain
      bovine alpha 4(IV) has 70, 59, 58, and 53% amino acid identity with human alpha
      2(IV), alpha 1(IV), alpha 5(IV), and alpha 3(IV), respectively. Alignment of the
      peptides also shows that alpha 4(IV) is most closely related to alpha 2(IV).
      Nevertheless, in the extreme COOH-terminal region of the NC1 domain there are
      structural features that are unique to alpha 4(IV). Cloning of the region of
      alpha 4(IV) that encodes the NC1 domain allows comparison of all five type IV
      collagens and highlights certain regions that are likely to be important in the
      specificities of NC1-NC1 interactions and in other discriminant functions of
      these molecules.

PMID- 1370462
TI  - Human transcription factor GATA-2. Evidence for regulation of preproendothelin-1
      gene expression in endothelial cells.
AB  - Previously, we showed that the promoter of the gene encoding preproendothelin-1
      (PPET-1) contains a GATA motif that is essential for activity and interacts with
      a nuclear factor similar in size and binding specificity to the erythroid
      transcription factor GATA-1. To identify this endothelial GATA-binding protein, a
      human endothelial cell cDNA library was screened with oligonucleotide probes for
      a portion of the zinc finger domain of GATA-1. A 2.6-kilobase cDNA encoding a 470
      amino acid protein was obtained. Sequence analysis revealed a predicted protein
      which is the human counterpart of a related chicken protein, designated GATA-2.
      Human GATA-2 is expressed by a variety of cells, including erythroid, HeLa, and
      endothelial cells. A complex of a GATA-containing probe and recombinant GATA-2
      expressed in COS cells comigrates with that present in gel shift experiments with
      nuclear extract derived from endothelial cells. In addition, expressed human GATA
      2 protein transactivates reporter gene constructs containing either minimal GATA
      promoter elements or the native PPET-1 promoter in a cotransfection assay.
      Retinoic acid treatment of endothelial cells results in down-regulation of GATA-2
      expression as well as down-regulation of PPET-1 gene expression. Human homologs
      of other known GATA-binding transcription factors are either absent from
      endothelial cells (in the case of GATA-1) or made in small quantities and not
      significantly affected by retinoid acid in these cells (in the case of GATA-3),
      making it unlikely that they regulate the PPET-1 gene. We propose that GATA-2 is
      the GATA-binding protein required for PPET-1 gene expression in endothelial
      cells.

PMID- 1370463
TI  - The effects of cysteine mutations on the reverse transcriptases of human
      immunodeficiency virus types 1 and 2.
AB  - Chemical modification of HIV-1 and HIV-2 (human immunodeficiency virus, types 1
      and 2) reverse transcriptases (RT) with three thiol reactive compounds
      selectively inhibits the RNase H function of the enzyme. HIV-1 RT has 2 cysteines
      (at positions 38 and 280); HIV-2 RT has 3 (38, 280, 445). Both of the cysteines
      in HIV-1 RT are in the polymerase domain. To investigate the role of the
      cysteines in the structure and function of the HIV RTs, we have converted each
      cysteine to serine and made combinations of the mutations. Since HIV-1 RT has
      alanine at position 445, we have also substituted alanine for serine at this
      position in HIV-2 RT. Neither of the single mutations in HIV-1 RT nor the double
      mutation mimics the effects of the chemical modification. The serine 280 mutation
      has little effect on either polymerase or RNase H; the serine 38 mutation affects
      both activities, as does the 38/280 double mutant. The 38 and 280 serine
      mutations in HIV-2 RT resemble the equivalent mutations in HIV-1 RT. Substitution
      of serine or alanine at position 445 (which lies in the RNase H domain)
      diminishes, but does not abolish, the RNase H activity of HIV-2 without affecting
      polymerase activity. The RNase H activity of a mutant HIV-1 RT with serine at
      position 280 is completely resistant to inactivation by the three thiol reactive
      compounds we tested, which demonstrates that cysteine 280 is the critical
      residue. We suggest that the reason the mutation (cysteine 280 to serine) does
      not mimic the chemical modification is because the chemical modification produces
      a greater change in the structure of the protein. We also suggest that position
      280 lies at or near the important points of contact between the RNase H and
      polymerase domains, so that chemical modification of this position, which lies
      within the polymerase domain, distorts the RNase H domain.

PMID- 1370464
TI  - NKD, a developmentally regulated tachykinin receptor in Drosophila.
AB  - A number of neuropeptides have been described which are present in the insect
      nervous system. The physiological role of these neuropeptides has not yet been
      clarified. We have characterized a Drosophila melanogaster cDNA coding for a
      protein, NKD, whose sequence resembles that of mammalian G protein-coupled
      neuropeptide receptors. This protein shows 38% homology with the mammalian
      tachykinin NK3 receptor within the transmembrane domain region. Stable cell lines
      expressing this cDNA are responsive to Locusta migratoria tachykinin but not to
      other peptides of the tachykinin family. The expression of this gene is detected
      principally in adult fly heads, but also in the adult body and in embryos.
      Interestingly, NKD mRNA is detected at very early stages of Drosophila embryonic
      development (3 h) and reaches the highest level of expression at 12-16 h, a time
      which correlates with the period of major neuronal development. In situ
      hybridization experiments demonstrate that NKD is expressed in the central
      nervous system, as well as in subsets of neurons in each segment of the
      developing ventral ganglia. The cytological localization of this gene is at
      position 86C on the Drosophila third chromosome.

PMID- 1370465
TI  - Characterization of a novel tumor necrosis factor-alpha-induced endothelial
      primary response gene.
AB  - The response of endothelial cells to the cytokine tumor necrosis factor-alpha
      (TNF) is complex, involving the induction and suppression of multiple genes and
      gene products. Differential screening of a TNF-stimulated, cycloheximide-treated
      human umbilical vein endothelial cell library has resulted in the cloning of
      several novel cDNAs whose protein products are involved in the primary response
      of the endothelium to TNF. One of these cDNAs, designated B12, is further
      characterized here. B12 is encoded by a 3.5-kilobase transcript and is induced
      rapidly and transiently by TNF. Transcript expression is found to be
      developmentally regulated in a tissue-specific manner, with B12 message being
      differentially expressed in the heart and liver during mouse embryogenesis. The
      open reading frame of B12 predicts a 316-amino acid sequence rich in charged
      residues, particularly at the carboxyl terminus, and has neither significant
      homology to other known proteins nor to any extent sequence motifs. B12 is found
      to be a highly conserved single-copy gene which is located in the q22----q23
      region of human chromosome 17. Polyclonal antibodies raised against a large
      portion of the B12 open reading frame immunoprecipitate a 36-kilodalton
      polypeptide from wheat germ lysates programmed to translate in vitro transcribed
      B12 mRNA. The B12 protein is further shown to be induced in human umbilical vein
      endothelial cells by TNF, and the protein is shown to be rapidly degraded.

PMID- 1370466
TI  - MARCKS protein is transcriptionally down-regulated in v-Src-transformed BALB/c
      3T3 cells.
AB  - Activation of protein kinase C (PKC) by tumor-promoting phorbol esters leads to
      the phosphorylation of an 80-kilodalton PKC substrate (known as MARCKS) in murine
      fibroblasts. In BALB/c 3T3 cells stably transformed by v-Src, phorbol esters were
      unable to induce phosphorylation of MARCKS. Western blot analysis and in vitro
      kinase assays showed that both PKC protein levels and kinase activity were
      unchanged in v-Src-transformed relative to the parental nontransformed BALB/c 3T3
      cells. However, MARCKS protein levels were reduced in v-Src-transformed cells
      relative to nontransformed cells. MARCKS RNA levels were also correspondingly
      reduced in v-Src-transformed cells. Nuclear "run-on" assays showed decreased
      transcription of MARCKS in v-Src-transformed cells. Thus, the absence of MARCKS
      in v-Src-transformed cells could be explained by a down-regulation of MARCKS
      transcription. Inhibiting the protein tyrosine kinase activity of v-Src with
      herbimycin A restored MARCKS RNA levels, MARCKS transcription, and MARCKS
      protein, suggesting that down-regulation of MARCKS in v-Src-transformed BALB/c
      3T3 cells is a direct effect of v-Src.

PMID- 1370467
TI  - A possible mechanism of inverse developmental regulation of alpha-fetoprotein and
      albumin genes. Studies with epidermal growth factor and phorbol ester.
AB  - Epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA)
      synergistically suppress activities of the promoter and enhancer of the human
      alpha-fetoprotein (AFP) gene in HuH-7 human hepatoma cells as analyzed by
      transient transfection assays using the chloramphenicol acetyltransferase gene as
      a reporter. In contrast to the AFP gene, albumin promoter and enhancer activities
      were not affected by EGF and TPA. Unexpectedly, however, Northern blot analysis
      revealed that the albumin mRNA level as well as the AFP mRNA level were reduced
      by treatment with EGF and TPA. We propose that in HuH-7 cells, the AFP enhancer
      stimulates the albumin promoter as well as the AFP promoter; and consequently,
      inhibition of the AFP enhancer by EGF and TPA results in reduction of both AFP
      and albumin mRNA levels. The significance of the involvement of the AFP enhancer
      in albumin transcription is discussed in relation to the inverse pattern of
      expression of the AFP and albumin genes in neonatal growth.

PMID- 1370469
TI  - The gene encoding the biotin carboxylase subunit of Escherichia coli acetyl-CoA
      carboxylase.
AB  - We report the molecular cloning and DNA sequence of the gene encoding the biotin
      carboxylase subunit of Escherichia coli acetyl-CoA carboxylase. The biotin
      carboxylase gene encodes a protein of 449 residues that is strikingly similar to
      amino-terminal segments of two biotin-dependent carboxylase proteins, yeast
      pyruvate carboxylase and the alpha-subunit of rat propionyl-CoA carboxylase. The
      deduced biotin carboxylase sequence contains a consensus ATP binding site and a
      cysteine-containing sequence preserved in all sequenced bicarbonate-dependent
      biotin carboxylases that may play a key catalytic role. The gene encoding the
      biotin carboxyl carrier protein (BCCP) subunit of acetyl-CoA carboxylase is
      located upstream of the biotin carboxylase gene and the two genes are
      cotranscribed. As previously reported by others, the BCCP sequence encoded a
      protein of 16,688 molecular mass. However, this value is much smaller than that
      (22,500 daltons) obtained by analysis of the protein. Amino-terminal amino acid
      sequencing of the purified BCCP protein confirmed the deduced amino acid sequence
      indicating that BCCP is a protein of atypical physical properties. Northern and
      primer extension analyses demonstrate that BCCP and biotin carboxylase are
      transcribed as a single mRNA species that contains an unusually long untranslated
      leader preceding the BCCP gene. We have also determined the mutational alteration
      in a previously isolated acetyl-CoA carboxylase (fabE) mutant and show the lesion
      maps within the BCCP gene and results in a BCCP species defective in acceptance
      of biotin. Translational fusions of the carboxyl-terminal 110 or 84 (but not 76)
      amino acids of BCCP to beta-galactosidase resulted in biotinated beta
      galactosidase molecules and production of one such fusion was shown to result in
      derepression of the biotin biosynthetic operon.

PMID- 1370468
TI  - An insulin-stimulated cation channel in skeletal muscle. Inhibition by calcium
      causes oscillation.
AB  - A cation channel has been identified in the plasma membrane of skeletal muscle
      that oscillates open and closed in a regular manner. In an experimental system of
      patch-clamped reconstituted plasma membrane in phospholipid bilayers, the
      oscillations are calcium-dependent and constitute regular closing events due to
      inhibition of the channel by calcium with a Ki of 2.2 +/- 1 x 10(-6) M, followed
      by reopening. There are 3.7 +/- 1 calcium binding sites/channel. With sodium as
      the current vehicle, conductance is increased by voltage, insulin (Km = 5 +/- 0.6
      x 10(-9) M), and hydrolyzable guanine nucleotides. Cyclic GMP alone with increase
      the conductance with a Km of 3.7 +/- 0.6 x 10(-7) M. In the absence of calcium,
      the unitary conductance with insulin + GTP or cGMP at 150 mM NaCl is 153
      picosiemens. Sodium current is insensitive to 10(-5) M tetrodotoxin but inhibited
      by mu-conotoxin (Ki = 5 x 10(-8) M). These findings in the reconstituted system
      were verified in patch-clamped whole muscle cells where an insulin and cGMP
      dependent sodium current inhibited by mu-conotoxin could be demonstrated. In the
      whole cell experiments, slow calcium-dependent oscillations of the sodium current
      were also detected.

PMID- 1370470
TI  - Reaction of Co(II)bleomycin with dioxygen.
AB  - The reaction of Co(II)bleomycin with dioxygen has been investigated. Dioxygen
      binds to the Co(II) complex within the time of mixing according to electron spin
      resonance and uv-visible spectroscopy and dioxygen analysis. Then, two
      dioxygenated cobalt centers react, releasing 1 mol of O2 and forming an
      intermediate characterized by a few highly shifted 1H NMR resonances and loss of
      the ESR spectrum. This is thought to be a dioxygen-bridged dimer of cobalt
      bleomycin molecules. Time-dependent absorbance and dioxygen measurements yield
      the same second order rate constant for this step of the reaction. According to
      uv-visible and NMR spectral analysis, the intermediate decays into diamagnetic
      products in a first order rate process. High performance liquid chromatography
      and 1H NMR studies demonstrate that the product contains two bleomycin species of
      equal concentration. One component is Co(III)bleomycin, designated Form II. The
      other is the peroxide adduct of Co(III)bleomycin, Form I, as determined by direct
      determination of hydrogen peroxide, which is slowly released from the product at
      low pH. In contrast, hydrogen peroxide is readily detected during the reaction of
      Co(II)Blm with O2. In isolation, Form I is unstable at pH 7 and is converted
      within 24 h into a mixture of Form I and Form II.

PMID- 1370471
TI  - Reaction of DNA-bound Co(II)bleomycin with dioxygen.
AB  - The aerobic oxidation of Co(II)bleomycin bound to calf thymus DNA has been
      investigated in relation to the mechanism of reaction in solution in the absence
      of DNA. Kinetics of dioxygenation of the Co(II) complex were followed by
      spectrophotometric and electron spin resonance spectroscopy as well as dioxygen
      analysis. The reaction is slower than when carried out in solution; its rate is
      inversely related to the ratio of DNA base pairs to Co(II)bleomycin. The
      subsequent oxidation reaction, observed spectrophotometrically and by dioxygen
      analysis, is second order in cobalt complex. The calculated second order rate
      constant is also inversely related to the base pair to metal complex ratio. Once
      this ratio exceeds three, the reaction rate slows significantly with each
      additional increment of DNA added to the starting reaction mixture. Taking
      advantage of the high stability of O(2)-Co(II)bleomycin bound to greater than a 3
      fold excess of DNA base pairs, it could be demonstrated that the rate constant
      for oxidation of two O(2)-Co(II)bleomycin molecules is much slower than that for
      O(2)-Co(II)bleomycin plus Co(II)bleomycin. With the same technique it was
      observed that the metal centers of O(2)-Co(II)bleomycin and Fe(II)bleomycin also
      undergo oxidation. The binding to DNA of both solution products of the oxidation
      of Co(II)bleomycin by O2 was examined by 1H NMR spectroscopy. Peroxy
      Co(III)bleomycin, Form I, binds with higher affinity than Co(III)bleomycin, Form
      II. At lower ionic strength, the size of the DNA binding site for each form is
      about 2 base pairs/molecule of drug.

PMID- 1370472
TI  - Hepatocyte-directed gene transfer in vivo leads to transient improvement of
      hypercholesterolemia in low density lipoprotein receptor-deficient rabbits.
AB  - Familial hypercholesterolemia is an inherited disease in humans, caused by a
      deficiency of low density lipoprotein (LDL) receptors, that we have used as a
      model for developing liver-directed gene therapies. Our strategy is to
      reconstitute hepatic LDL receptor expression in vivo by administering a DNA
      protein complex that is capable of targeting the delivery of functional LDL
      receptor genes to hepatocytes. Infusion of this DNA-protein complex into the
      peripheral circulation of a rabbit animal model for familial hypercholesterolemia
      resulted in hepatocyte-specific gene transfer and a temporary amelioration of
      hypercholesterolemia. This noninvasive approach to gene therapy should have
      applications in the treatment of a wide spectrum of human diseases.

PMID- 1370473
TI  - Characterization of guanosine diphospho-D-mannose dehydrogenase from Pseudomonas
      aeruginosa. Structural analysis by limited proteolysis.
AB  - Alginate is believed to be a major virulence factor in the pathogenicity of
      Pseudomonas aeruginosa in the lungs of patients suffering from cystic fibrosis.
      Guanosine diphospho-D-mannose dehydrogenase (GDPmannose dehydrogenase, EC
      1.1.1.132) is a key enzyme in the alginate biosynthetic pathway which catalyzes
      the oxidation of guanosine diphospho-D-mannose (GDP-D-mannose) to GDP-D
      mannuronic acid. In this paper, we report the structural analysis of GMD by
      limited proteolysis using three different proteases, trypsin, submaxillary Arg-C
      protease, and chymotrypsin. Treatment of GMD with these proteases indicated that
      the amino-terminal part of this enzyme may fold into a structural domain with an
      apparent molecular mass of 25-26 kDa. Multiple proteolytic cleavage sites existed
      at the carboxyl-terminal end of this domain, indicating that this segment may
      represent an exposed region of the protein. Initial proteolysis also generated a
      carboxyl-terminal fragment with an apparent molecular mass of 16-17 kDa which was
      further digested into smaller fragments by trypsin and chymotrypsin. The
      proteolytic cleavage sites were localized by partial amino-terminal sequencing of
      the peptide fragments. Arg-295 was identified as the initial cleavage site for
      trypsin and Tyr-278 for chymotrypsin. Catalytic activity of GMD was totally
      abolished by the initial cleavage. However, binding of the substrate, GDP-D
      mannose, increased stability toward proteolysis and inhibited the loss of enzyme
      activity. GMP and GDP (guanosine 5'-mono- and diphosphates) also blocked the
      initial cleavage, but NAD and mannose showed no effect. These results suggest
      that binding of the guanosine moiety at the catalytic site of GMD may induce a
      conformational change that reduces the accessibility of the cleavage sites to
      proteases. Binding of [14C]GDP-D-mannose to the amino-terminal domain was not
      affected by the removal of the carboxyl-terminal 16-kDa fragment. Furthermore,
      photoaffinity labeling of GMD with [32P]arylazido-beta-alanine-NAD followed by
      proteolysis demonstrated that the radioactive NAD was covalently linked to the
      amino-terminal domain. These observations imply that the amino-terminal domain
      (25-26 kDa) contains both the substrate and cofactor binding sites. However, the
      carboxyl-terminal fragment (16-17 kDa) may possess amino acid residues essential
      for catalysis. Thus, proteolysis had little effect on substrate binding, but
      totally eliminated catalysis. These biochemical data are in complete agreement
      with amino acid sequence analysis for the existence of substrate and cofactor
      sites of GMD. A linear peptide map of GMD was constructed for future
      structure/functional studies.

PMID- 1370474
TI  - The NusA and NusG proteins of Escherichia coli increase the in vitro readthrough
      frequency of a transcriptional attenuator preceding the gene for the beta subunit
      of RNA polymerase.
AB  - The genes for the beta (rpoB) and beta' (rpoC) subunits of Escherichia coli RNA
      polymerase are the distal members of a complex transcriptional unit that contains
      four upstream ribosomal protein genes. The RNA polymerase subunit genes are
      transcribed at a lower frequency than the ribosomal protein genes as a result of
      termination at an attenuator preceding rpoB. A purified in vitro transcription
      system was developed using linear DNA templates that carry the attenuator. The
      ability of known termination and antitermination proteins to modulate termination
      at the attenuator was tested. Both NusA and NusG increase the frequency of
      transcriptional readthrough at the attenuator whereas NusB, S10, and Rho had no
      significant effect in this system.

PMID- 1370475
TI  - Molecular cloning and enzymatic analysis of the rat homolog of "PhK-gamma T," an
      isoform of phosphorylase kinase catalytic subunit.
AB  - Messenger RNA encoding a protein kinase closely related to the catalytic subunit
      of skeletal muscle phosphorylase kinase has previously been isolated from a human
      HeLa cell cDNA library, and cross-species Northern hybridization analysis has
      shown that the rat homolog of this transcript is abundant in the adult testis
      (Hanks, S.K. (1989) Mol. Endocrinol. 3, 110-116). We now propose that the protein
      encoded by this transcript be designated as "PhK-gamma T." In this article, the
      primary structure of the rat homolog of PhK-gamma T is described, as deduced from
      nucleotide sequences of cDNA and genomic clones. RNase protection analysis
      reveals that PhK-gamma T transcripts are actually present in a wide variety of
      adult rat tissues, but at levels 20-100-fold less than what is observed in the
      testis. In the testis, transcription of the PhK-gamma T gene is initiated at
      multiple sites as shown by RNase protection and primer extension. Enzymatic
      activity of PhK-gamma T was demonstrated using renatured bacterially expressed
      protein. In the presence of Ca2+/calmodulin, PhK-gamma T is able to efficiently
      phosphorylate glycogen phosphorylase and convert it from an inactive to an active
      form. We conclude that PhK-gamma T represents a true isoform of phosphorylase
      kinase catalytic subunit.

PMID- 1370476
TI  - Inhibition of CD3-linked phospholipase C by phorbol ester and by cAMP is
      associated with decreased phosphotyrosine and increased phosphoserine contents of
      PLC-gamma 1.
AB  - The mechanisms by which phorbol 12-myristate 13-acetate (PMA) and cAMP attenuate
      the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P2) induced
      by ligation of the T-cell antigen receptor complex (TCR) was studied in the human
      Jurkat T-cell line. It has previously been shown that stimulation of Jurkat cells
      with antibodies to CD3, components of the TCR, elicits a rapid and transient
      phosphorylation of phospholipase C (PLC)-gamma 1, the predominant PLC isozyme in
      Jurkat cells, at multiple tyrosine residues and that such tyrosine
      phosphorylation leads to activation of PLC-gamma 1. Prior incubation of Jurkat
      cells with PMA or forskolin, which increases intracellular cAMP concentrations,
      prevented tyrosine phosphorylation of PLC-gamma 1 as well as the hydrolysis of
      PtdIns 4,5-P2 induced by ligation of CD3. Dose-response curves of PMA and of
      forskolin for the inhibition of PLC-gamma 1 tyrosine phosphorylation and of
      PtdIns 4,5-P2 hydrolysis were similar. These results suggest that the inhibition
      of PtdIns 4,5-P2 hydrolysis by PMA and cAMP is attributable to reduced tyrosine
      phosphorylation of PLC-gamma 1. Treatment of Jurkat cells with PMA or forskolin
      stimulated the phosphorylation of PLC-gamma 1 at serine 1248. PMA treatment also
      elicited the phosphorylation of PLC-gamma 1 at an unidentified serine site.
      Phosphopeptide map analysis indicated that the sites of PLC-gamma 1
      phosphorylated in Jurkat cells treated with PMA and forskolin are the same as
      those phosphorylated in vitro by protein kinase C (PKC) and cAMP-dependent
      protein kinase (PKA), respectively. Stimulation of Jurkat cells with antibodies
      to CD3 also elicited phosphorylation of PLC-gamma 1 at serine 1248 and at the
      unidentified serine site phosphorylated in PLC-gamma 1 from PMA-treated cells.
      Thus, phosphorylation of PLC-gamma 1 by PKC or PKA at serine 1248 may modulate
      the interaction of PLC-gamma 1 with the protein tyrosine kinase or the protein
      tyrosine phosphatase; this altered interaction may, at least in part, be
      responsible for the decreased tyrosine phosphorylation of PLC-gamma 1 seen in PMA
      and forskolin-treated Jurkat cells. Furthermore, in the absence of PMA,
      activation of PKC by diacylglycerol provides a negative feedback signal
      responsible for reducing the phosphotyrosine contents of PLC-gamma 1.

PMID- 1370477
TI  - Patterns of prohormone processing. Order revealed by a new procholecystokinin
      derived peptide.
AB  - An 83-amino acid cholecystokinin peptide with a sulfated tyrosine and an amidated
      carboxyl terminus (CCK-83) was purified from human intestinal mucosa. The
      purified peptide was chemically characterized, and its bioactivity was compared
      to CCK-8. Several post-translational processing steps such as cleavage at basic
      residues, sulfation, and amidation are necessary to form biologically active
      cholecystokinin from its nascent prepropeptide. The discovery of CCK-83 gives new
      insight into the order of preprohormone processing. The processing of prepro-CCK
      appears to be in the order of: 1) signal peptidase cleavage, 2) tyrosine
      sulfation, 3) cleavage after a carboxyl-terminal pair of basic residues, 4)
      carboxypeptidase B-like cleavage of these basic residues, 5) amidation (which
      results in the formation of CCK-83), and 6) cleavage at monobasic residues by
      endopeptidases (which results in the smaller molecular forms of cholecystokinin).
      The characterization of biologically active CCK-83 with a sulfated tyrosine and
      an amidated carboxyl terminus establishes the site of signal peptidase action and
      suggests an order of post-translational modifications that give rise to the
      various molecular forms of cholecystokinin.

PMID- 1370478
TI  - Human gastric cathepsin E gene. Multiple transcripts result from alternative
      polyadenylation of the primary transcripts of a single gene locus at 1q31-q32.
AB  - Genomic clones containing portions of the human cathepsin E (CTSE) gene were
      isolated from cosmid and lambda recombinant libraries. The regions corresponding
      to coding, the 5'- and 3'-untranslated, and the exon-intron boundaries of the
      CTSE gene were identified by sequence and hybridization analysis. The size and
      placement of the nine exons found in the 17.5-kilobase CTSE gene was highly
      conserved relative to other aspartic proteinases and provided additional evidence
      that these proteinases are derived from a common ancestral gene. Segregation and
      linkage analysis of two informative restriction fragment length polymorphisms
      (MspI and DraI) indicated that there is a single human CTSE locus located at
      chromosome 1q31-q32 which is closely linked to the renin gene. Three CTSE
      transcripts (3.6, 2.6, and 2.1 kilobases) were identified in gastric fundic and
      antral mucosa poly (A+) RNA, and these appeared identical in size and relative
      abundance to those contained in poly(A+) RNA from cultured gastric adenocarcinoma
      cell lines containing CTSE. Sequence analysis of cDNA clones and comparison with
      the 3'-flanking untranslated region in genomic clones provided evidence that
      alternative polyadenylation of the primary transcript resulted in the 2.6- and
      2.1-kilobase transcripts which constituted greater than 95% of CTSE transcripts
      found in the stomach.

PMID- 1370479
TI  - Expression and chromosomal localization of the gene for the human transcriptional
      repressor GCF.
AB  - GCF is a human transcriptional regulator that represses transcription of certain
      genes and is encoded by a 3-kilobase (kb) mRNA (Kageyama, R., and Pastan, I.
      (1989) Cell 59, 815-825). The expression of GCF was examined in a variety of
      clonal cell lines. The 3.0-kb GCF mRNA was found to be expressed at the highest
      level in HUT 102 cells (derived from a T-cell lymphoma). Elevated levels of the
      GCF mRNA were also noted in KATO III and AGS (gastric carcinomas), FEM-X
      (melanoma), and U266B1 (myeloma) cell lines. A human fibroblast cell line (WI38)
      did not express GCF mRNA, and no cross-hybridization to a mouse cell line (NIH
      3T3) or monkey cell line (CV-1) could be detected. The GCF cDNA also hybridizes
      to RNA species of 4.5 and 1.2 kb. The 4.5-kb RNA has the same general expression
      pattern as the GCF mRNA. Hybridization of cellular RNA with various probes
      derived from the 3-kb cDNA revealed that the 4.5-kb RNA species only hybridizes
      to GCF cDNA probes from the extreme 5' end. By using single-stranded RNA probes,
      hybridization to the three RNA species was detected with the antisense probe for
      the 5' end (nucleotides 1-561). The single-stranded antisense probe for the
      region encompassing nucleotides 561-1692 hybridized to the 3.0- and 1.2-kb RNA
      species. The sense probes for these regions did not hybridize to these RNAs. The
      GCF gene was localized to a single locus, the chromosome 2 p11.1-11.2 region, by
      in situ hybridization. Treatment of human KB epidermoid carcinoma cells with
      phorbol 12-myristate 13-acetate (PMA) lead to a rapid induction of GCF RNA after
      1 h and a decline to lower than control levels after 6 h. Epidermal growth factor
      receptor mRNAs were not increased by PMA until 2 h after treatment and were at
      their highest level only after GCF mRNAs were decreased. The 4.5- and 1.2-kb RNAs
      were also induced by PMA with the same kinetics as the GCF mRNA. These results
      show that the GCF gene is widely expressed in human tissues and cell lines and
      that the 4.5- and 1.2-kb RNAs have similar expression patterns.

PMID- 1370480
TI  - Cloning and expression of a cardiac/brain beta subunit of the L-type calcium
      channel.
AB  - The skeletal muscle dihydropyridine receptor/Ca2+ channel is composed of five
      protein components (alpha 1, alpha 2 delta, beta, and gamma). Only two such
      components, alpha 1 and alpha 2, have been identified in heart. The present study
      reports the cloning and expression of a novel beta gene that is expressed in
      heart, lung, and brain. Coexpression of this beta with a cardiac alpha 1 in
      Xenopus oocytes causes the following changes in Ca2+ channel activity: it
      increases peak currents, accelerates activation kinetics, and shifts the current
      voltage relationship toward more hyperpolarized potentials. It also increases
      dihydropyridine binding to alpha 1 in COS cells. These results indicate that the
      cardiac L-type Ca2+ channel has a similar subunit structure as in skeletal
      muscle, and provides evidence for the modulatory role of the beta subunit.

PMID- 1370482
TI  - Okadaic acid mimics multiple changes in early protein phosphorylation and gene
      expression induced by tumor necrosis factor or interleukin-1.
AB  - Okadaic acid, a phosphatase inhibitor from a marine organism, mimics tumor
      necrosis factor/interleukin-1 (TNF/IL-1) in inducing changes in early cellular
      protein phosphorylation. A total of approximately 116 proteins exhibit
      significant and concordant changes in phosphorylation or dephosphorylation within
      15 min in human fibroblasts activated by either okadaic acid, TNF, or IL-1. The
      fidelity of this mimicry by okadaic acid extends to the phosphorylation of the 27
      hsp complex, stathmin, eIF-4E, myosin light chain, nucleolin, epidermal growth
      factor receptor, and other cdc2-kinase substrates (c-abl, RB, and p53). The
      okadaic acid-induced pattern of protein phosphorylation is distinct from that
      observed in cells treated with phorbol 12-myristate 13-acetate or with ligands
      like epidermal growth factor, cyclic AMP agonists, bradykinin, or interferons.
      Like TNF, okadaic acid also induces the transcription of immediate early response
      genes like c-jun and Egr-1 as well as the interleukin-6 genes. The overall early
      effects of okadaic acid uniquely parallel those of TNF/IL-1 and not those of
      other cytokines or ligands. Regulation of protein phosphatase inhibition is
      discussed as a mechanism for TNF/IL-1 signal transduction.

PMID- 1370481
TI  - Retinoids and retinoid-binding protein expression in rat adipocytes.
AB  - Adipose tissue has been reported to contain relatively high levels of the
      specific mRNA for retinol-binding protein (RBP) (Makover A., Soprano, D.R.,
      Wyatt, M. L., and Goodman, D.S. (1989) J. Lipid Res. 30, 171-180). Studies were
      conducted to explore retinoid and retinoid-binding protein storage and metabolism
      in adipose tissue. In these studies, we measured RBP and cellular retinol-binding
      protein (CRBP) mRNA levels and retinoid levels in 6 adipose depots in male rats.
      Total RNA was isolated from inguinal, dorsal, mesenteric, epididymal,
      perinephric, and brown adipose tissue, and average RBP and CRBP mRNA levels were
      determined by Northern blot analysis. The relative levels of RBP mRNA in these 6
      anatomically different adipose depots averaged, respectively, 6.3, 6.7, 16, 34,
      37, and 21% of the level in a rat liver RNA standard. Retinoid levels in the 6
      depots were similar and averaged approximately 6-7 micrograms of retinol eq/g of
      adipose tissue. Since adipose tissue contains several cell types, the cellular
      localizations of RBP and CRBP expression and retinoid storage were examined. RNA
      was prepared from isolated rat adipocytes and stromal-vascular cells. Cellular
      levels of the mRNAs for RBP, CRBP, apolipoprotein E (apoE), lipoprotein lipase,
      adipocyte P2, and adipsin were measured by Northern blot analysis. RBP was
      expressed almost exclusively in the adipocytes and only weakly in the stromal
      vascular cells. Both CRBP and apoE mRNA levels were relatively high in the
      stromal-vascular cell preparations and only very low mRNA levels were found in
      the adipocytes. Lipoprotein lipase, adipsin, and adipocyte P2 mRNAs were found in
      substantial levels in both the adipocytes and stromal-vascular cells, but with
      higher levels present in the adipocytes. Cultured adipocytes synthesized RBP
      protein and secreted it into the medium. Only adipocytes (not stromal-vascular
      cells) contained retinol, at levels between 0.65-0.8 micrograms of retinol
      eq/10(6) cells. These studies demonstrate that adipocytes store retinoid and
      synthesize and secrete RBP, and suggest that rat adipocytes may be dynamically
      involved in retinoid storage and metabolism.

PMID- 1370483
TI  - Primary structure of rat pulmonary surfactant protein D. cDNA and deduced amino
      acid sequence.
AB  - Surfactant protein D (SP-D) is a carbohydrate-binding glycoprotein containing a
      collagen-like domain that is synthesized by alveolar type II epithelial cells.
      The complete primary structure of rat SP-D has been determined by sequencing of a
      cloned cDNA. The protein consists of three regions: an NH2-terminal segment of 25
      amino acids, a collagen-like domain consisting of 59 Gly-X-Y repeats, and a COOH
      terminal carbohydrate recognition domain of 153 amino acids. There are 6 cysteine
      residues present in rat SP-D: 2 in the NH2-terminal noncollagenous segment and 4
      in the COOH-terminal carbohydrate-binding domain. The collagenous domain contains
      one possible N-glycosylation site. The protein is preceded by a cleaved, NH2
      terminal signal peptide. SP-D shares considerable homology with the C-type
      mammalian lectins. Hybridization analysis demonstrates that rat SP-D is encoded
      by a 1.3-kilobase mRNA which is abundant in lung and highly enriched in alveolar
      type II cells. Extensive homology exists between rat SP-D and bovine conglutinin.

PMID- 1370484
TI  - Three distinct RNAs for the surface protease gp63 are differentially expressed
      during development of Leishmania donovani chagasi promastigotes to an infectious
      form.
AB  - Leishmania sp. protozoa contain an abundant surface protease (gp63) that is
      important for the virulence of the parasite. We found that the average amount of
      gp63 expressed by Leishmania donovani chagasi promastigotes increases 6-11-fold
      as they develop from a less infectious form in logarithmic phase to a highly
      infectious form during stationary phase of cultivation in vitro. The predominant
      gp63 RNA switches from a 2.7 to a 3.0 kilobase (kb) RNA during the transition
      from log to stationary phase. Sequence analysis of gp63 cDNAs reveals that three
      different classes of gp63 RNAs, containing unique 3'-untranslated regions (3'
      UTRs), are expressed during growth to stationary phase. The predominant 2.7-(log)
      and 3.0-kb (stationary) class gp63 RNAs possess nearly identical coding regions,
      but they diverge in their 3' UTRs. A third class, consisting of 3.1- and 2.6-kb
      (constitutive) gp63 RNAs, is expressed at low levels throughout cultivation. This
      latter class encodes a gp63 with an additional 41 amino acids at its C terminus,
      replacing a potential signal for attachment of a glycolipid membrane anchor with
      a sequence that could be a transmembrane region. These findings are consistent
      with the regulated expression of different gp63 genes, resulting in different
      amounts of gp63 protein, during the promastigote's in vitro development to an
      infectious form.

PMID- 1370485
TI  - Modulation of the carbohydrate moiety of thyroglobulin by thyrotropin and calcium
      in Fisher rat thyroid line-5 cells.
AB  - Thyroglobulin secreted in the medium by Fisher rat thyroid line-5 (FRTL-5) cells
      cultured in the presence of thyroid stimulating hormone (TSH) shows a slower
      electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and a higher density position in a CsCl gradient than
      thyroglobulin secreted by FRTL-5 cells cultured in the absence of TSH for 5-7
      days. Such a TSH effect is much less or not evident when secreted thyroglobulin
      is digested with peptide N-glycohydrolase F or when intracellular thyroglobulin
      is compared. Intracellular thyroglobulin migrates faster than thyroglobulin
      secreted either in the presence or in the absence of TSH. Evaluation of the
      mannose and galactose content of thyroglobulin demonstrates that intracellular
      thyroglobulin has more mannose and less galactose than extracellular
      thyroglobulin; it also shows that TSH decreases the mannose content of
      thyroglobulin while increasing its galactose content. Bio-Gel P6 chromatography
      shows that TSH increases the complex type carbohydrate chains while decreasing
      the high mannose chains in the secreted thyroglobulin. High mannose type
      oligosaccharides were characterized by fast atom bombardment-mass spectrometry
      analysis. Treatment with the calcium ionophore A23187 (5 microM) of FRTL-5 cells
      cultured with or without TSH causes the appearance of a "fast" migrating form of
      thyroglobulinin in the culture medium. Bio-Gel P6 chromatography shows that
      A23187 causes a dramatic decrease of the complex carbohydrate chains of the
      secreted thyroglobulin.

PMID- 1370486
TI  - Hepatitis B virus envelope L protein particles. Synthesis and assembly in
      Saccharomyces cerevisiae, purification and characterization.
AB  - The hepatitis B virus envelope gene encodes three transmembrane proteins in
      frame; S, the product of S gene; M, the product of M (pre-S2 + S) gene; and L,
      the product of L (pre-S1 + pre-S2 + S) gene. Unlike the S and M proteins,
      attempts to efficiently synthesize L proteins and assemble them into L protein
      particles in various eukaryotic cells have been unsuccessful, probably because of
      the presence of the pre-S1 peptide with an unknown function which appears to be
      inhibitory to the host secretory apparatus. To investigate the role of the pre-S1
      peptide, we constructed an L gene fused with a synthetic gene for chicken
      lysozyme signal peptide (C-SIG) at the 5'-terminal and placed the resultant gene
      under the control of the yeast glyceraldehyde-3-phosphate dehydrogenase gene
      promoter. After the fused-C-SIG peptide was correctly processed by the yeast
      secretory apparatus, a yeast transformant synthesized a protein with a molecular
      mass of approximately 52 kDa at a level of 42% of the total soluble protein.
      Electron micrographic observation showed that the gene products assembled into 23
      nm spherical and filamentous particles. The pre-S peptide of the gene product was
      deposited into the endoplasmic reticulum (ER) lumen and well-glycosylated. It
      seemed that the gene products were accumulated as particles in certain specific
      membrane structures of the yeast secretory apparatus. Moreover, both the amount
      of mRNAs specific for the L gene and the in vivo stability of the synthesized L
      proteins did not change significantly by the addition of the C-SIG gene. These
      findings indicated that, if the pre-S1 peptide penetrates the ER membrane
      efficiently, the L proteins can be synthesized cotranslationally, translocate
      across the ER membrane with its S region, and then assemble by themselves into
      the particle form. Therefore, the pre-S1 peptide may involve weak or reduced
      signal peptide activity for recognition by the secretory apparatus and/or for the
      transport of the pre-S peptide into the ER lumen.

PMID- 1370487
TI  - Four novel members of the connexin family of gap junction proteins. Molecular
      cloning, expression, and chromosome mapping.
AB  - We have used low stringency hybridization and polymerase chain reaction (PCR)
      amplification with degenerate oligonucleotides to identify four new members of
      the rat connexin gene family. On the basis of their predicted molecular mass,
      these proteins have been designated connexin (Cx) 40 (Cx40), Cx37, Cx33, and
      Cx31.1. The new connexins exhibit all of the conserved structural features of the
      connexin family, including highly similar extracellular and transmembrane domains
      but divergent major cytoplasmic domains. On the basis of primary sequence
      similarity, the connexin family may be divided into two classes. Cx40, Cx37, and
      Cx33 are similar to the previously characterized Cx43 and Cx46. Cx31.1 is similar
      to Cx26, Cx31, and Cx32. Cx37 and Cx40 mRNAs are expressed in a wide variety of
      adult organs and tissues, with particular abundance in lung. However, their
      relative levels are different in many organs and thus their distribution is not
      completely coincident. Cx33 and Cx31.1 genes exhibit a much more restricted
      pattern of expression; mRNAs are detected only in testes and skin, respectively.
      Chromosomal mapping studies indicate that Cx26 and Cx46 are tightly linked on
      chromosome 14, and Cx37 and Cx31.1 are linked on chromosome 4, while the rest of
      the connexin genes are dispersed.

PMID- 1370488
TI  - Biochemical characterization of the cystic fibrosis transmembrane conductance
      regulator in normal and cystic fibrosis epithelial cells.
AB  - Affinity-purified polyclonal antibodies, raised against two synthetic peptides
      corresponding to the R domain and the C terminus of the human cystic fibrosis
      transmembrane conductance regulator (CFTR), were used to characterize and
      localize the protein in human epithelial cells. Employing an immunoblotting
      technique that ensures efficient detection of large hydrophobic proteins, both
      antibodies recognized and approximately 180-kDa protein in cell lysates and
      isolated membranes of airway epithelial cells from normal and cystic fibrosis
      (CF) patients and of T84 colon carcinoma cells. Reactivity with the anti-C
      terminus antibody, but not with the anti-R domain antibody, was eliminated by
      limited carboxypeptidase Y digestion. When normal CFTR cDNA was overexpressed via
      a retroviral vector in CF or normal airway epithelial cells or in mouse
      fibroblasts, the protein produced had an apparent molecular mass of about 180
      kDa. The CFTR expressed in insect (Sf9) cells by a baculovirus vector had a
      molecular mass of about 140 kDa, probably representing a nonglycosylated form.
      The CFTR in epithelial cells appears to exist in several forms. N-glycosidase
      treatment of T84 cell membranes reduces the apparent molecular mass of the major
      CFTR band from 180 kDa to 140 kDa, but a fraction of the T84 cell CFTR could not
      be deglycosylated, and the CFTR in airway epithelial cell membranes could not be
      deglycosylated either. Moreover, wheat germ agglutinin absorbs the majority of
      the CFTR from detergent-solubilized T84 cell membranes but not from airway cell
      membranes. The CFTR in all epithelial cell types was found to be an integral
      membrane protein not solubilized by high salt or lithium diiodosalicylate
      treatment. Sucrose density gradient fractionation of crude membranes prepared
      from the airway epithelial cells, previously surface-labeled by enzymatic
      galactosidation, showed a plasma membrane localization for both the normal CFTR
      and the CFTR carrying the Phe508 deletion (delta F 508). The CFTR in all cases co
      localized with the Na+, K(+)-ATPase and the plasma membrane calcium ATPase, while
      the endoplasmic reticulum calcium ATPase and mitochondrial membrane markers were
      enriched at higher sucrose densities. Thus, the CFTR appears to be localized in
      the plasma membrane both in normal and delta F 508 CF epithelial cells.

PMID- 1370490
TI  - Nuclear protein import is inhibited by an antibody to a lumenal epitope of a
      nuclear pore complex glycoprotein.
AB  - Gp210 is a major transmembrane glycoprotein associated with the nuclear pore
      complex that is suggested to be important for organizing pore complex
      architecture and assembly. A mouse monoclonal IgG directed against an epitope in
      the lumenal domain of rat gp210 was expressed in cultured rat cells by
      microinjection of mRNA prepared from a hybridoma cell line. The expressed IgG,
      which becomes assembled into a functional antibody in the lumen of the
      endoplasmic reticulum, bound to the nuclear envelope in vivo. Expression of anti
      gp210 antibody in interphase cells specifically reduced approximately fourfold
      the mediated nuclear import of a microinjected nuclear protein (nucleoplasmin)
      coupled to gold particles. The antibody also significantly decreased nuclear
      influx of a 10-kD dextran by passive diffusion. This transport inhibition did not
      result from removal of pore complexes from nuclear membranes or from gross
      alterations in pore complex structure, as shown by EM and immunocytochemistry. A
      physiological consequence of this transport inhibition was inhibition of cell
      progression from G2 into M phase. Hence, binding of this antibody to the lumenal
      side of gp210 must have a transmembrane effect on the structure and functions of
      the pore complex. These data argue that gp210 is directly or indirectly connected
      to pore complex constituents involved in mediated import and passive diffusion.

PMID- 1370491
TI  - A synthetic peptide representing the consensus sequence motif at the carboxy
      terminal end of the rod domain inhibits intermediate filament assembly and
      disassembles preformed filaments.
AB  - All intermediate filament (IF) proteins share a highly conserved sequence motif
      at the COOH-terminal end of their rod domains. We have studied the influence of a
      20-residue peptide, representing the consensus motif on filament formation and
      stability. Addition of the peptide at a 10-20-fold molar excess over keratins K8
      plus K18 had a severe effect on subsequent IF assembly. Filaments displayed a
      rough surface and variable diameters with a substantial amount present in
      unravelled form. At higher peptide concentration (50-100-fold molar excess), IF
      formation was completely inhibited and instead only loose aggregates of
      "globular" particles were formed. The peptide also influenced performed keratin
      IF in a dose-dependent manner. While a three-fold molar excess was sufficient to
      cause partial fragmentation of IF, a 50-fold molar excess caused complete
      disassembly within 5 min. Loosely associated protofibrils, short needlelike IF
      fragments, and aggregates of globular particles were detected. The motif peptide
      also caused the disassembly of filaments formed by desmin, a type III IF protein.
      Peptide concentrations and incubation times required for complete disassembly
      were somewhat higher than for the filaments containing K8 plus K18. A 50-fold
      molar excess was sufficient to cause complete disassembly within 1 h. Peptides
      unrelated in sequence to the motif did not interfere with filament formation or
      stability even when present for more than 12 h at a 100-fold molar excess. The
      results suggest that the motif sequence normally binds to a specific acceptor
      site for which the motif peptide can successfully compete. Taken together with
      current models of IF structure the results indicate that normal binding of the
      motif sequence to its acceptor must play an essential role in IF formation,
      possibly by directing the proper alignment of neighboring tetramers or
      protofilaments. Finally we show that in vitro formed IF are much more sensitive
      and dynamic strutures than previously thought.

PMID- 1370489
TI  - cAMP and Ca(2+)-mediated secretion in parotid acinar cells is associated with
      reversible changes in the organization of the cytoskeleton.
AB  - The potential involvement of actin and fodrin (brain spectrin) in secretory
      events has been assessed in primary cultured guinea pig parotid acinar cells,
      using as a tool affinity purified anti-alpha-fodrin antibody, phalloidin, and
      immunofluorescence techniques. In resting parotid acinar cells fodrin and actin
      appeared as a continuous ring under the plasma membrane of most of the cells.
      Upon stimulation with secretagogues fodrin and actin labeling at the level of the
      plasma membrane disappeared almost completely. To establish a correlation between
      secretion and cytoskeletal changes at the individual cell level, anti-alpha
      amylase-antibodies were used to label secreted amylase exposed at the surface of
      secreting cells. The number of cells expressing alpha-amylase on their surface
      followed bulk secretion of alpha-amylase. A strict correlation between secretion
      and alteration of the actin-fodrin labeling was observed at the individual cell
      level. The cytoskeletal changes occurred in parallel with secretion independently
      of the secretagogue used (carbamoylcholine in the presence of Ca2+, isoproterenol
      in presence or absence of Ca2+, forskolin, or dibutyryl-cyclic-AMP). The changes
      were reversible upon removal of the secretagogue. Since Ca2+, as well as cAMP
      mediated secretion, was associated with the same kind of cytoskeletal changes, a
      reorganization of the cytoskeleton may play an essential part in regulated
      secretion.

PMID- 1370492
TI  - Association of the tyrosine phosphorylated epidermal growth factor receptor with
      a 55-kD tyrosine phosphorylated protein at the cell surface and in endosomes.
AB  - After the intraportal injection of EGF, the EGF receptor (EGFR) is rapidly
      internalized into hepatic endosomes where it remains largely receptor bound (Lai
      et al., 1989. J. Cell Biol. 109:2751-2760). In the present study, we evaluated
      the phosphotyrosine content of EGFRs at the cell surface and in endosomes in
      order to assess the consequences of internalization. Quantitative estimates of
      specific radioactivity of the EGFR in these two compartments revealed that
      tyrosine phosphorylation of the EGFR was observed at the cell surface within 30 s
      of ligand administration. However, the EGFR was also highly phosphorylated in
      endosomes reaching levels of tyrosine phosphorylation significantly higher than
      those of the cell surface receptor at 5 and 15 min after EGF injection. A 55-kD
      tyrosine phosphorylated polypeptide (pyp55) was observed in association with the
      EGFR at the cell surface within 30 s of EGF injection. The protein was also found
      in association with the EGFR in endosomes as evidenced by coprecipitation studies
      using a mAb to the EGFR as well as by coelution with the EGR in gel permeation
      chromatography. Limited proteolysis of isolated endosomes indicated that the
      tyrosine phosphorylated domains of the EGFR and associated pyp55 were
      cytosolically oriented while internalized EGF was intraluminal. The
      identification of pyp55 in association with EGFR in both hepatic plasma membranes
      and endosomes may be relevant to EGFR function and/or trafficking of the EGFR.

PMID- 1370493
TI  - Membrane fusion process of Semliki Forest virus. I: Low pH-induced rearrangement
      in spike protein quaternary structure precedes virus penetration into cells.
AB  - The Semliki Forest virus (SFV) directs the synthesis of a heterodimeric membrane
      protein complex which is used for virus membrane assembly during budding at the
      surface of the infected cell, as well as for low pH-induced membrane fusion in
      the endosomes when particles enter new host cells. Existing evidence suggests
      that the E1 protein subunit carries the fusion potential of the heterodimer,
      whereas the E2 subunit, or its intracellular precursor p62, is required for
      binding to the nucleocapsid. We show here that during virus uptake into acidic
      endosomes the original E2E1 heterodimer is destabilized and the E1 proteins form
      new oligomers, presumably homooligomers, with altered E1 structure. This altered
      structure of E1 is specifically recognized by a monoclonal antibody which can
      also inhibit penetration of SFV into host cells as well as SFV-mediated cell-cell
      fusion, thus suggesting that the altered E1 structure is important for the
      membrane fusion. These results give further support for a membrane protein
      oligomerization-mediated control mechanism for the membrane fusion potential in
      alphaviruses.

PMID- 1370494
TI  - Inhibition of cell adhesion by high molecular weight kininogen.
AB  - An anti-cell adhesion globulin was purified from human plasma by heparin-affinity
      chromatography. The purified globulin inhibited spreading of osteosarcoma and
      melanoma cells on vitronectin, and of endothelial cells, platelets, and
      mononuclear blood cells on vitronectin or fibrinogen. It did not inhibit cell
      spreading on fibronectin. The protein had the strongest antiadhesive effect when
      preadsorbed onto the otherwise adhesive surfaces. Amino acid sequence analysis
      revealed that the globulin is cleaved (kinin-free) high molecular weight
      kininogen (HKa). Globulin fractions from normal plasma immunodepleted of high
      molecular weight kininogen (HK) or from an individual deficient of HK lacked
      adhesive activity. Uncleaved single-chain HK preadsorbed at neutral pH, HKa
      preadsorbed at pH greater than 8.0, and HKa degraded further to release its
      histidine-rich domain had little anti-adhesive activity. These results indicate
      that the cationic histidine-rich domain is critical for anti-adhesive activity
      and is somehow mobilized upon cleavage. Vitronectin was not displaced from the
      surface by HKa. Thus, cleavage of HK by kallikrein results in both release of
      bradykinin, a potent vasoactive and growth-promoting peptide, and formation of a
      potent anti-adhesive protein.

PMID- 1370495
TI  - Motility of fibronectin receptor-deficient cells on fibronectin and vitronectin:
      collaborative interactions among integrins.
AB  - Cells are capable of adhering to and migrating on protein components of the
      extracellular matrix. These cell-matrix interactions are thought to be mediated
      largely through a family of cell surface receptors termed integrins. However, the
      manner in which individual integrins are involved in cell adhesion and motility
      has not been fully determined. To explore this issue, we previously selected a
      series of CHO variants that are deficient in expression of the integrin alpha 5
      beta 1, the "classical" fibronectin receptor. Two sets of subclones of these
      variants were defined which respectively express approximately 20% or 2% of
      fibronectin receptor on the cell surface when compared to wild-type cells
      (Schreiner, C. L., J. S. Bauer, Y. N. Danilov, S. Hussein, M. M. Sczekan, and R.
      L. Juliano. 1989. J. Cell Biol. 109:3157-3167). In the current study, the variant
      clones were tested for haptotactic motility on substrata coated with fibronectin
      or vitronectin. Data from assays using fibronectin show that cellular motility of
      the 20% variants was substantially decreased (30-75% of wild type), while the
      motility of the 2% variants was nearly abolished (2-20% of wild type).
      Surprisingly, a similar pattern was seen for haptotactic motility of both 2% and
      20% variants when vitronectin was used (approximately 20-30% of wild type). The
      reduced haptotactic motility of the fibronectin receptor-deficient variant clones
      on vitronectin was shown not to be due to reduced vitronectin receptor (alpha v
      beta 3) expression nor to a failure of these variants to adhere to vitronectin
      substrata. Transfection of the deficient variants with a cDNA for the human alpha
      5 subunit resulted in normal levels of fibronectin receptor expression (as a
      human alpha 5/hamster beta 1 chimera) and restored the motility of the CHO
      variants on fibronectin and vitronectin. This indicates that expression of the
      alpha 5 subunit is required for normal haptotactic motility on vitronectin
      substrata and suggests that the fibronectin receptor (alpha 5 beta 1) plays a
      cooperative role with vitronectin receptors in cell motility.

PMID- 1370496
TI  - A monoclonal antibody to beta 1 integrin (CD29) stimulates VLA-dependent
      adherence of leukocytes to human umbilical vein endothelial cells and matrix
      components.
AB  - The leukocyte beta 1 integrin receptor very late activation antigen-4 (VLA-4)
      (alpha 4 beta 1, CD49d/CD29) binds to vascular cell adhesion molecule-1 (VCAM-1)
      expressed on cytokine-activated endothelium. A mAb designated 8A2 was identified
      that stimulated the binding of U937 cells to CHO cells transfected with VCAM-1
      cDNA but not endothelial-leukocyte adhesion molecule or CD4 cDNA. mAb 8A2 also
      rapidly stimulated the adherence of peripheral blood lymphocytes (PBLs) to VCAM-1
      transfected CHO cells or recombinant human tumor necrosis factor-treated human
      umbilical vein endothelial cells. mAb 8A2-stimulated binding of PBL was inhibited
      by mAbs to VLA-4 or VCAM-1. Surface expression of VLA-4 was not altered by mAb
      8A2 treatment and monovalent Fab fragments of mAb 8A2 were active.
      Immunoprecipitation studies reveal that mAb 8A2 recognizes beta 1-subunit (CD29)
      of integrin receptors. In contrast to mAbs directed to VLA-4 alpha-subunit (alpha
      4, CD49d), mAb 8A2 did not induce homotypic aggregation of PBL. Additionally, mAb
      8A2 stimulated adherence of PBL and hematopoietic cell lines to purified matrix
      components laminin and fibronectin. This binding was blocked by mAbs to the VLA
      alpha-subunits alpha 6 (CD49f), or alpha 5 (CD49e) and alpha 4 (CD49d),
      respectively. We conclude that mAb 8A2 modulates the affinity of VLA-4 and other
      leukocyte beta 1 integrins, and should prove useful in studying the regulation of
      beta 1 integrin function.

PMID- 1370497
TI  - P-selectin, a granule membrane protein of platelets and endothelial cells,
      follows the regulated secretory pathway in AtT-20 cells.
AB  - P-selectin (PADGEM, GMP-140, CD62) is a transmembrane protein specific to alpha
      granules of platelets and Weibel-Palade bodies of endotheial cells. Upon
      stimulation of these cells, P-selectin is translocated to the plasma membrane
      where it functions as a receptor for monocytes and neutrophils. To investigate
      whether the mechanism of targeting of P-selectin to granules is specific for
      megakaryocytes and endothelial cells and/or dependent on von Willebrand factor, a
      soluble adhesive protein that is stored in the same granules, we have expressed
      the cDNA for P-selectin in AtT-20 cells. AtT-20 cells are a mouse pituitary cell
      line that can store proteins in a regulated fashion. By double-label
      immunofluorescence, P-selectin was visible as a punctate pattern at the tips of
      cell processes. This pattern closely resembled the localization of ACTH, the
      endogenous hormone produced and stored by the AtT-20 cells. Fractionation of the
      transfected cells resulted in the codistribution of P-selectin and ACTH in
      cellular compartments of the same density. Immunoelectron microscopy using a
      polyclonal anti-P-selectin antibody demonstrated immunogold localization in dense
      granules, morphologically indistinguishable from the ACTH granules. Binding
      experiments with radiolabeled monoclonal antibody to P-selectin indicated that
      there was also surface expression of P-selectin on the AtT-20 cells. After
      stimulation with the secretagogue 8-Bromo-cAMP the surface expression increased
      twofold, concomitant with the release of ACTH. In contrast, the surface
      expression of P-selectin transfected into CHO cells, which do not have a
      regulated pathway of secretion, did not change with 8-Br-cAMP treatment. In
      conclusion, we provide evidence for the regulated secretion of a transmembrane
      protein (P-selectin) in a heterologous cell line, which indicates that P-selectin
      contains an independent sorting signal directing it to storage granules.

PMID- 1370501
TI  - Characterization of the effects of human placental HGF on rat hepatocytes.
AB  - Hepatocyte growth factor (HGF) also known as hepatopoietin A (HPTA)
      (Michalopoulos, FASEB J., 4:176-187, 1990) is a heparin-binding growth factor
      whose characterization and tissue distribution have been reported elsewhere. This
      growth factor was recently cloned and its amino acid sequence determined under
      the name of hepatocyte growth factor (HGF) (Miyazawa et al., Biochem. Biophys.
      Res. Commun., 163:967-973, 1989; Zarnegar et al., Biochem. Biophys. Res. Commun.,
      163:1370-1376, 1989; Nakamura et al., Nature, 342:440-443, 1989). Human placenta
      is one of the tissues that contains significant amounts of HGF. We isolated HGF
      from human placenta and characterized its biologic effect on rat hepatocytes.
      Human placenta HGF was isolated in high purity as a single chain molecule. Single
      chain HGF stimulated DNA synthesis in primary rat hepatocyte cultures in serum
      free medium. The maximal effect was seen at 5-10 ng/ml. The maximal response
      occurred at 25-48 hours after plating of the hepatocytes. Protein synthesis was
      also stimulated by HGF in primary rat hepatocyte cultures. There were peak
      responses at 19-24 and 37-42 hours after plating of the hepatocytes. TGF beta 1
      inhibited more than 95% of HGF-induced DNA synthesis but only 25% of HGF-induced
      protein synthesis. HGF interacted in an additive manner with EGF, a well-known
      hepatocyte mitogen. There was not an additive interaction between HGF and aFGF.
      Regenerating liver hepatocytes obtained from rats which underwent two-thirds
      partial hepatectomies (PHX) also responded to HGF in a dose-dependent manner as
      the hepatocytes from normal liver.

PMID- 1370498
TI  - Binding of monoclonal antibody AA4 to gangliosides on rat basophilic leukemia
      cells produces changes similar to those seen with Fc epsilon receptor activation.
AB  - The mAb AA4 binds to novel derivatives of the ganglioside Gd1b on rat basophilic
      leukemia (RBL-2H3) cells. Some of the gangliosides are located close to the high
      affinity IgE receptor (Fc epsilon RI), and binding of mAb AA4 inhibits Fc epsilon
      RI-mediated histamine release. In the present study, mAb AA4 was found to bind
      exclusively to mast cells in all rat tissues examined. In vitro, within 1 min of
      mAb AA4 binding, the cells underwent striking morphologic changes. They lost
      their normal spindle shaped appearance, increased their ruffling, and spread over
      the surface of the culture dish. These changes were accompanied by a
      redistribution of the cytoskeletal elements, actin, tubulin, and vimentin, but
      only the actin was associated with the membrane ruffles. Binding of mAb AA4 also
      induces a rise in intracellular calcium, stimulates phosphatidyl inositol
      breakdown, and activates PKC. However, the extent of these changes was less than
      that observed when the cells were stimulated with antigen or antibody directed
      against the Fc epsilon RI. None of these changes associated with mAb AA4 binding
      were seen when the cells were exposed to nonspecific IgG, IgE, or four other anti
      cell surface antibodies, nor were the changes induced by binding mAb AA4 at 4
      degrees C or in the absence of extracellular calcium. Although mAb AA4 does not
      stimulate histamine release, it enhances the effect of the calcium ionophore
      A23187 mediated release. The morphological and biochemical effects produced by
      mAb AA4 are similar to those seen following activation of the cell through the
      IgE receptor. Therefore, the surface gangliosides which bind mAb AA4 may function
      in modulating secretory events.

PMID- 1370499
TI  - Phorbol ester-induced actin assembly in neutrophils: role of protein kinase C.
AB  - The shape changes and membrane ruffling that accompany neutrophil activation are
      dependent on the assembly and reorganization of the actin cytoskeleton, the
      molecular basis of which remains to be clarified. A role of protein kinase C
      (PKC) has been postulated because neutrophil activation, with the attendant shape
      and membrane ruffling changes, can be initiated by phorbol esters, known
      activators of PKC. It has become apparent, however, that multiple isoforms of PKC
      with differing substrate specificities exist. To reassess the role of PKC in
      cytoskeletal reorganization, we compared the effects of diacylglycerol analogs
      and of PKC antagonists on kinase activity and on actin assembly in human
      neutrophils. Ruffling of the plasma membrane was assessed by scanning EM, and
      spatial redistribution of filamentous (F)-actin was assessed by scanning confocal
      microscopy. Staining with NBD-phallacidin and incorporation of actin into the
      Triton X-100-insoluble ("cytoskeletal") fraction were used to quantify the
      formation of (F)-actin. [32P]ATP was used to detect protein phosphorylation in
      electroporated cells. Exposure of neutrophils to 4 beta-PMA (an activator of PKC)
      induced protein phosphorylation, membrane ruffling, and assembly and
      reorganization of the actin cytoskeleton, whereas the 4a-isomer, which is
      inactive towards PKC, failed to produce any of these changes. Moreover, 1,2
      dioctanoylglycerol, mezerein, and 3-(N-acetylamino)-5-(N-decyl-N-methylamino)
      benzyl alcohol, which are nonphorbol activators of PKC, also promoted actin
      assembly. Although these effects were consistent with a role of PKC, the
      following observations suggested that stimulation of conventional isoforms of the
      kinase were not directly responsible for actin assembly: (a) Okadaic acid, an
      inhibitor of phosphatases 1 and 2A, potentiated PMA-induced protein
      phosphorylation, but not actin assembly; and (b) PMA-induced actin assembly and
      membrane ruffling were not prevented by the conventional PKC inhibitors 1-(5
      isoquinolinesulfonyl)-2-methylpiperazine, staurosporine, calphostin C, or
      sphingosine at concentrations that precluded PMA-induced protein phosphorylation
      and superoxide production. On the other hand, PMA-induced actin assembly was
      inhibited by long-chain fatty acid coenzyme A esters, known inhibitors of nuclear
      PKC (nPKC). We conclude that PMA-induced actin assembly is unlikely to be
      mediated by the conventional isoforms of PKC, but may be mediated by novel
      isoforms of the kinase such as nPKC.

PMID- 1370500
TI  - Adhesion of a chicken myeloblast cell line to fibrinogen and vitronectin through
      a beta 1-class integrin.
AB  - The adhesive interactions of circulating blood cells are tightly regulated,
      receptor-mediated events. To establish a model for studies on regulation of cell
      adhesion, we have examined the adhesive properties of the HD11 chick myeloblast
      cell line. Function-perturbing antibodies were used to show that integrins
      containing the beta 1 subunit mediate HD11 cell attachment to several distinct
      extracellular matrix proteins, specifically fibronectin, collagen, vitronectin,
      and fibrinogen. This is the first evidence that an integrin heterodimer in the
      beta 1 family functions as a receptor for fibrinogen. While the alpha v beta 1
      heterodimer has been shown to function as a vitronectin receptor on some cells,
      this heterodimer could not be detected on HD11 cells. Instead, results suggest
      that the beta 1 subunit associates with different, unidentified alpha subunit(s)
      to form receptors for vitronectin and fibrinogen. Results using function-blocking
      antibodies also demonstrate that on these cells, additional receptors for
      vitronectin are formed by alpha v beta 3 and alpha v associated with an
      unidentified 100-kD beta subunit. The adhesive interactions of HD11 cells with
      these extracellular matrix ligands were shown to be regulated by
      lipopolysaccharide treatment, making the HD11 cell line attractive for studies of
      mechanisms regulating cell adhesion. In contrast to primary macrophage which
      rapidly exhibit enhanced adhesion to laminin and collagen upon activation,
      activated HD11 cells exhibited reduced adhesion to most extracellular matrix
      constituents.

PMID- 1370502
TI  - Responsiveness of RNA degradation to amino acids in cultured rat hepatocytes:
      comparison with isolated rat hepatocytes.
AB  - The role of amino acids in the regulation of RNA degradation was investigated in
      cultured hepatocytes from fed rats previously labeled in vivo with [6-14C]orotic
      acid. Rates of RNA degradation were determined between 42 and 48 h of culture
      from the release of radioactive cytidine in the presence of 0.5 mM unlabeled
      cytidine. The fractional rate was about 4.4 +/- 0.4%/h in the absence of amino
      acids (0x). The catabolism of RNA was decreased to basal level (1.5 +/- 0.3%/h)
      by the addition of amino acids at 10 times normal plasma concentration (10x). The
      inhibition of RNA degradation, expressed as percentage of maximal deprivation
      induced response (0x minus 10x), averaged 60% at normal plasma levels of amino
      acids. The degree of responsiveness was greatly improved as compared to freshly
      isolated hepatocytes (20%) and was similar to the sensitivity previously observed
      with perfused livers. In cultured hepatocytes, the sensitivity of RNA degradation
      to amino acids was not affected by varying the volume of medium from 1 to 4 ml
      per dish. In freshly isolated hepatocytes, the inhibitory effect of amino acids
      was not modified by changing the cell density from 0.5 to 5 x 10(6) cells per ml.
      In the range of normal plasma concentration of amino acids, the low sensitivity
      of RNA degradation in isolated hepatocytes persisted with inhibition ranging from
      10 to 20%. These findings suggest that the control of RNA degradation in both
      cultured and isolated hepatocytes is not affected by the total quantity of amino
      acids available in the medium, but their concentration is crucial. Electron
      microscopy observations and the inhibitory effect of 3-methyl-adenine in cultured
      rat hepatocytes partially confirmed the role of the lysosomal system in the
      increase of RNA degradation and its regulation by amino acids.

PMID- 1370503
TI  - Derivatized dextrans mimic heparin as stabilizers, potentiators, and protectors
      of acidic or basic FGF.
AB  - Acidic and basic fibroblast growth factors (aFGF and bFGF) belong to a family of
      structurally related polypeptides characterized by a high affinity for heparin. a
      and bFGF display mitogenic activity for many cell types. Biological activity is
      strongly potentiated by heparin which stabilizes their molecular conformation by
      preventing physicochemical or enzymatic degradation. In our previous study we
      have shown that a water-soluble derivatized dextran named DDE, containing 82.2%
      methyl carboxylic acid groups, 6.1% benzylamide, and 5.6% sulfonate with a
      specific anticoagulant activity equivalent to heparin of 0.5 IU/mg could
      potentiate the mitogenic activity of aFGF on CCL39 cells. Optimal concentrations
      for maximal potentiation of 400 micrograms/ml and 20 micrograms/ml were obtained
      respectively for DDE and heparin. In the present report, we have uncovered the
      fact that several carboxymethyl benzylamide sulfonate dextrans differing in
      degree and positioning of the substituent groups can mimic heparin in regard to
      the protection, stabilization, and potentiating effects with aFGF or bFGF. Our
      data establishes that the dextran derivatives studied can act as potentiating
      agents for FGFs. Native dextran (DDA) had no effect. Dextran derivatives can also
      protect aFGF and bFGF from heat as well as from pH denaturation, and against
      trypsic and chymotrypsic degradation. The dextran derivative DDI (82%
      methylcarboxylic acid, 23% benzylamide, 13% sulfonate) was studied in greater
      detail and exhibited a greater protection for bFGF and a lesser protecting effect
      for aFGF than heparin. Derivatized dextrans which have very weak anticoagulant
      activity are of great interest as alternatives to heparin for use as stabilizers,
      potentiators, protectants, and slow-release matrices for FGFs in pharmaceutical
      formulations.

PMID- 1370504
TI  - Monkey retinal pigment epithelial cells in vitro synthesize, secrete, and degrade
      insulin-like growth factor binding proteins.
AB  - Cultured monkey retinal pigment epithelial (RPE) cells rapidly secrete large
      amounts of insulin-like growth factor binding proteins (IGF-BPs). IGF-II tracer
      binding activity in conditioned media is two to three times greater than that of
      IGF-I. Under reducing SDS-PAGE conditions, 125I-IGF affinity-crosslinked binding
      protein (BP) is visualized as a broad band between 36 +/- 2.9 and 49 +/- 3.3 kDa.
      Because the electrophoretic mobility of the crosslinked BP is increased under non
      reducing conditions (33-45 kDa), intramolecular sulfhydryl bonding may be
      present. Frequently, the radiographic band representing affinity-crosslinked
      binding protein exhibits a complex pattern of non-uniform densities that suggests
      structural or functional IGF-BP micro-heterogeneity. IGF-BPs synthesized by RPE
      also exhibit heterogeneity with respect to the absence or presence of
      oligosaccharide side chains. In particular, the larger, but not the mid-sized or
      smaller IGF-BPs exhibit side chains linked to the core protein with N-glycosidic
      linkage. None of the crosslinked IGF-BPs exhibit O-linked side chains. Long-term
      (12, 24, 48 hr) conditioning studies revealed that IGF-BP fails to accumulate in
      culture media beyond 12 hr, but that replacement of conditioned media with fresh
      media allows a second period of binding protein accumulation. Other short-term
      (12 hr) experiments indicate that, in fresh medium, the levels of IGF-BP increase
      during the first 6-8 hr and then remain stable. To examine the processes
      contributing to these steady state levels of IGF-BP, aliquots of 8-hr conditioned
      medium were removed from the cells and either frozen on dry ice or incubated at
      37 degrees C for 16 hr. Importantly, it was found that incubation at 37 degrees C
      resulted in a near total loss of binding activity. This is the first report of
      IGF-BP degrading activity in a cell culture system. These findings indicate that
      1) primate RPE cells rapidly secrete a complex mixture of N-glycosylated and non
      glycosylated IGF-BPs, and 2) the steady state levels of secreted IGF-BP are
      tightly regulated at least in part through a concomitant IGF-BP inactivating
      activity. Cultured RPE cells may be of utility in examining the mechanisms of IGF
      BP synthesis, secretion, and degradation at the cellular level.

PMID- 1370505
TI  - The spectrum of sickle cell disease.

PMID- 1370506
TI  - The role of cyclic adenosine 3',5'-monophosphate and polyol metabolism in
      diabetic neuropathy.
AB  - The effects of a stable prostacyclin analog, Iloprost, and aldose reductase
      inhibitors (ONO-2235 and isoliquiritigenin) were studied to elucidate the role of
      cAMP in diabetic neuropathy in relation to polyol metabolism. In in vivo
      experiments, the cAMP and myoinositol contents in sciatic nerves and motor nerve
      conduction velocity were significantly reduced in diabetic rats. Iloprost
      significantly restored the reduced cAMP content in sciatic nerves and improved
      motor nerve conduction velocity in diabetic rats. However, the contents of
      sorbitol or myoinositol in sciatic nerves were not affected by Iloprost in
      diabetic rats. On the other hand, aldose reductase inhibitors significantly
      reduced the sorbitol content and increased the cAMP and myoinositol contents in
      the sciatic nerves of diabetic rats. The motor nerve conduction velocity was also
      slightly but significantly improved by treatment with aldose reductase
      inhibitors. There was a negative correlation between cAMP and sorbitol in the
      sciatic nerves of diabetic rats treated with aldose reductase inhibitors and a
      positive correlation between cAMP and motor nerve conduction velocity. In in
      vitro experiments, Iloprost significantly increased cAMP, but did not affect the
      sorbitol content in sciatic nerves. Aldose reductase inhibitors inhibited
      sorbitol accumulation and increased cAMP in sciatic nerves. Our data suggest that
      polyol pathway activation somehow results in cAMP reduction in sciatic nerves and
      that the reduction of cAMP in peripheral nerves may be closely related to the
      pathogenesis of diabetic neuropathy.

PMID- 1370507
TI  - Concordant suppression of serum immunoreactive luteinizing hormone (LH), follicle
      stimulating hormone, alpha subunit, bioactive LH, and testosterone in
      postmenopausal women by a potent gonadotropin releasing hormone antagonist
      (detirelix).
AB  - The purposes of the current study were 2-fold: 1) to assess the effects of a new
      antagonistic analog of GnRH [N-Ac-D-Nal(2)1, D-pC1-phe2, D-Trp3, D-hArg (Et2)6, D
      Ala10] GnRH, or detirelix (Syntex Research) on gonadotrope function as reflected
      by serum levels of immuno- and bioassayable LH, and immunoactive FSH and alpha
      subunit concentrations in postmenopausal, hypergonadotropic women; and 2) to
      determine if androgen production in the postmenopausal ovary is gonadotropin
      dependent. Six normal postmenopausal women were studied. Each volunteer received
      doses of 1, 5, and 20 mg detirelix sc in a random order separated by at least a 1
      week interval. Serum LH, FSH, and alpha-subunit were measured by RIA at frequent
      intervals for 72 h after each injection. Bioactive LH levels were measured at 0,
      24, 48, and 72 h after injection by a mouse Leydig cell bioassay, to permit
      comparison of biological with immunological LH activity. The steroids
      testosterone (T) and dehydroepiandrosterone sulfate were measured before
      injection and 12 (T only), 24 and 48 h after injection of the 20 mg dose.
      Immunoactive levels of serum LH and FSH were both suppressed in a dose-dependent
      manner, but LH suppression was greater than that of FSH. Maximum LH suppression
      (mean +/- SEM) after the 1, 5, and 20 mg doses was 40.2 +/- 7.0%, 63.2 +/- 3.4%,
      and 75.8 +/- 2.2%, respectively. For the same doses, maximum FSH suppression was
      18.0 +/- 6.0%, 25.6 +/- 4.6%, and 39.6 +/- 2.7%. LH levels remained suppressed
      below baseline for up to 72 h after the 20 mg dose. Bioactive LH changes closely
      paralleled those of immunoactive LH. Mean LH suppression (area under the serum
      concentration curve) during the first 24 h after injection was 23.5 +/- 6.2% for
      the 1-mg dose, 47.2 +/- 4.7% for the 5-mg dose, and 61.0 +/- 2.1% for the 20-mg
      dose. Mean percent FSH suppression during the first 24 h, calculated in the same
      manner, was 6.8 +/- 3.9% (1 mg), 14.5 +/- 2.9% (5 mg), and 18.2 +/- 2.6% (20 mg).
      Serum alpha-subunit concentrations were significantly suppressed by 1 h after
      dosing with the 5- and 20-mg doses (P less than 0.05), and remained suppressed
      throughout the 72-h sampling period. Gonadotropin dependence of steroidogenesis
      in the postmenopausal ovary was suggested by a significant suppression of serum T
      concentrations after the 20-mg dose of detirelix.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1370508
TI  - Human granulosa-luteal and cumulus cells express transforming growth factors-beta
      type 1 and type 2 mRNA.
AB  - Human granulosa-luteal cells and cumulus cells obtained from women undergoing in
      vitro fertilization and embryo transfer (IVF-ET) were examined for the presence
      of TGF-beta 1 and TGF-beta 2 mRNA by reverse transcription-polymerase chain
      reaction (RT-PCR) analysis. RT-PCR analysis revealed that both follicle cell
      types express mRNA for both TGF-beta subtypes. Verification of RT-PCR products
      was done by restriction enzyme digestion analysis. These results suggest a
      role(s) for TGF-beta 1 and TGF-beta 2 in the development of human granulosa
      luteal cells and the oocyte-cumulus cell complex.

PMID- 1370510
TI  - Allergic rhinitis to ragweed pollen. I. Reassessment of the effects of
      immunotherapy on cellular and humoral responses.
AB  - This work presents a double-blind, placebo-controlled study of 27 patients with
      allergic rhinitis to ragweed who received preseasonal desensitization
      immunotherapy [IT] with alum-precipitated aqueous ragweed extracts. We reassessed
      the following parameters in relation to clinical responses: clinical scores,
      nasal reactivity to a provocative dose of ragweed causing a 75% fall in airflow
      rate (PD75), ragweed IgE and IgG, and ragweed-induced basophil histamine release
      (BHR). First, the nasal PD75 correlated with the severity of nasal symptoms (p
      less than 0.05). Second, we confirmed a significant symptomatic improvement in
      the IT-treated group either by clinical scores (p less than 0.05) or the
      prevention of the seasonal fall of the PD75 (p less than 0.005). Also, IT reduced
      the seasonal rise of IgE (p less than 0.02) and induced an increase in IgG (p
      less than 0.01) and a decrease in BHR (p less than 0.03). There was a significant
      correlation between IgE and BHR (r = 0.80; p less than 0.01). After selecting out
      the effects of IgE, the BHR was still higher in the placebo-treated group than in
      the IT-treated group (p less than 0.02), suggesting the involvement of other
      modulating factors. Symptomatic improvement after IT correlated only with the
      summation of both IgE and BHR (PD75; r = 0.64; p less than 0.005). This
      observation suggests that the severity of clinical symptoms is determined by
      several interacting factors and not by the antibody response alone.

PMID- 1370509
TI  - Evaluation of cutaneous responses and lung function from exposure to opiate
      compounds among ethical narcotics-manufacturing workers.
AB  - We recently demonstrated morphine-6-hemisuccinate-human serum albumin conjugate
      (M-6-HS-HSA)-specific IgG in serum from ethic narcotics-manufacturing workers. In
      this article, we present results of epicutaneous tests to opiate compounds and
      lung-function studies in these same workers. Thirty-nine workers, exposed to
      opiates, were evaluated for possible work-related changes in lung function and
      were administered a questionnaire concerning opiate exposure and health history
      in February 1988. In December 1988, 33 employees with occupational exposure to
      opiates, six other workers (New Jersey referent) employed at the same factory
      with minimal exposure to opiate compounds, and 17 nonexposed individuals from
      Cincinnati, Ohio, were subjected to epicutaneous threshold testing with a panel
      of six opiate compounds and nine common aeroallergens. In opiate-exposed workers,
      significantly lower epicutaneous threshold concentrations were detected (compared
      to New Jersey referent and Cincinnati control subjects) for dihydrocodeine (p
      less than 0.01), hydrocodone (p less than 0.05), codeine (p less than 0.01), and
      morphine (p less than 0.05). Significant associates existed among epicutaneous
      threshold concentrations between the agents tested; that is, individuals with a
      positive morphine skin test would generally have a positive codeine skin test,
      etc. Atopic status (positive cutaneous test results to two or more of nine common
      aeroallergens) was not significantly associated (p greater than 0.05) with
      positive opiate skin sensitivity. Although the mean cross-shift decrements in
      FEV1 for all workers were nonsignificant, five opiate-exposed individuals
      demonstrated cross-shift decrements in FEV1 of greater than 10%. Daily maximum
      minus-minimum changes in workweek PEFR (PEFRmax-min) were significantly reduced
      for Monday through Thursday (p less than 0.05) compared to PEFRmax-min changes
      during a nonwork, nonexposure 3-day weekend. Ten exposed workers demonstrated
      daily PEFRmax-min changes of greater than 20%, suggesting acute airway
      obstruction. Increased cutaneous reactivity to opiate compounds among opiate
      exposed workers may reflect development of pharmacologic hyperresponsiveness to
      opiate compounds.

PMID- 1370511
TI  - Allergic rhinitis to ragweed pollen. II. Modulation of histamine-releasing factor
      production by specific immunotherapy.
AB  - A number of cytokines, including histamine-releasing factors (HRFs), have a role
      to play in IgE-mediated asthma. However, the influence of HRF in allergic
      rhinitis without asthma remains to be revealed. This article presents a double
      blind, placebo-controlled study on the role of HRF in ragweed-allergic rhinitis
      and its modulation by natural pollen exposure and specific immunotherapy (IT).
      Twenty-seven patients allergic to ragweed were randomly assigned to receive
      either preseasonal alum-precipitated aqueous extracts of ragweed or placebo.
      Before the onset of therapy and during the ragweed-pollen season, subjects were
      evaluated for each of the following: clinical scores, ragweed IgE and IgG
      antibody levels, and spontaneous and allergen-driven HRF production. Thirteen
      nonatopic volunteers were also studied in the same protocol. First, before the
      initiation of therapy, more HRF was produced by both unstimulated and ragweed
      stimulated mononuclear cells (MNCs) of atopic subjects as compared to MNCs of
      nonatopic subjects. Second, MNCs of the placebo-treated group produced
      significantly more spontaneous and ragweed-specific HRF during the pollen season
      compared to the preseasonal values. Finally, specific IT not only improved the
      clinical manifestation of allergy but also prevented the seasonal rise of
      spontaneous and ragweed-driven HRF production, along with a well-known change in
      other immunologic parameters associated with successful IT.

PMID- 1370512
TI  - CD58 and CD59 molecules exhibit potentializing effects in T cell adhesion and
      activation.
AB  - We have generated stable Chinese hamster ovary (CHO) cell transfectants
      expressing either CD58 or CD59 or both molecules to compare their respective
      parts played in T cell adhesion and activation. Using a rosetting assay, we have
      shown the following: 1) The CD59 molecule was directly responsible for adhesive
      interaction between human T cells and CD59+ CHO transfectants. CD59-mediated
      adhesion induced 12 +/- 2% (mean +/- SEM, n = 25) of rosettes. 2) The CD58
      molecule expressed on CD58+ CHO transfectants induced 29 +/- 6% (mean +/- SEM, n
      = 8) of rosettes. 3) Double transfected CD58+CD59+ CHO cells formed up to 80% of
      rosettes, largely exceeding the sum of rosettes formed by single transfectants,
      thus disclosing at least an additive and possibly a synergic action of both
      molecules in mediating adhesion to T cells. Culturing purified human T cells in
      the presence of fixed CHO transfectants and submitogenic doses of PHA + rIL-1
      alpha showed that: 1) CD59+ CHO transfectants induced sevenfold T cell
      proliferation enhancement, demonstrating the direct involvement of the CD59
      molecule in T cell activation; 2) CD58+ CHO transfectants induced 20-fold T cell
      proliferation increase; and 3) the enhancement induced by CD58+CD59+ CHO cells
      was more than 40-fold. These results suggest that CD58 and CD59 molecules present
      on the surface of accessory cells might exert synergic function in T cell
      adhesive interactions and in the stimulation of T cell activation.

PMID- 1370513
TI  - Physical association of CD4 with the T cell receptor.
AB  - The coreceptor hypothesis postulates that physical association of CD4 with the
      TCR is required for effective signaling for T cell activation. A variety of
      studies has suggested that the coreceptor function of CD4 allows responses to 10-
      to 100-fold lower levels of peptide:self MHC class II ligand. We test the
      hypothesis of CD4 physical association with the TCR in two different ways. First,
      we use a panel of soluble antibodies directed at different TCR epitopes to
      activate a cloned T cell line, and show that activation by antibodies directed at
      a particular TCR epitope can be inhibited by anti-CD4 antibodies binding to a
      certain CD4 epitope. These effects establish that the interaction of CD4 and the
      TCR occurs in a specific orientation. Second, we use the same system to provide
      evidence that the physical association of CD4 with the TCR is required for
      effective tyrosine phosphorylation of the TCR zeta-chain subunit, presumably
      reflecting delivery of p56lck (lck) to the TCR. Only anti-TCR antibodies that
      induce physical association of CD4 with the TCR as monitored by cocapping can
      induce efficient tyrosine-phosphorylation of the TCR zeta-chain, unless second
      antibodies are used to force CD4 and the TCR to associate. Furthermore, the
      phosphorylation of the TCR zeta-chain exactly parallesl physical association in
      time and drug sensitivity. We conclude from these studies that stimuli that drive
      physical association of CD4 and the TCR strongly favor T cell activation,
      supporting the coreceptor hypothesis of CD4 function.

PMID- 1370514
TI  - T cell activation-inducing epitopes of the house dust mite allergen Der p I.
      Proliferation and lymphokine production patterns by Der p I-specific CD4+ T cell
      clones.
AB  - Cloned human CD4+ T cell lines specific for the house dust mite Dermatophagoides
      pteronyssinus were used to map minimal T cell activation-inducing epitopes on the
      Group I allergen in D. pteronyssinus extracts (Der p I) molecule. Most of these
      Der p I-specific T cell clones expressed different TCR V alpha and V beta gene
      products. Using recombinant deletion proteins, three T cell epitopes were
      identified on the Der p I molecule; p45-67 and p117-143 were recognized by HLA
      DR7-restricted T cells, whereas p94-104 was recognized in the context of HLA-DR2,
      DRw11 (DR5), and -DR8 molecules. This degenerate class II MHC restriction appears
      to be due to shared Phe and Asp residues at positions 67 and 70, respectively, in
      the third variable domain of the HLA-DR beta chain. All three T cell epitopes
      induced Th2-like cytokine production profiles by the Der p I-specific T cell
      clones, which were characterized by the production of very high levels of IL-4
      and IL-5, as compared with those secreted by tetanus toxin-specific T cell clones
      derived from the same patients, but no or low amounts of IL-2 and IFN-gamma. This
      Th2-like production profile was, however, not an intrinsic property of the Der p
      I-specific T cells, but was dependent upon their mode of activation. Stimulation
      with Con A also induced very low or no measurable levels of IL-2 and IFN-gamma,
      whereas activation with TPA and the calcium ionophore A23187 resulted in the
      production of high levels of IL-4, IL-5, IL-2, and IFN-gamma. These results
      indicate that Der p I-specific T cell clones are not defective in their capacity
      to produce high levels of Th1 cytokines.

PMID- 1370515
TI  - T cell receptor sequences from encephalitogenic T cells in adult Lewis rats
      suggest an early ontogenic origin.
AB  - In the Lewis rat, the encephalitogenic determinant of myelin basic protein (MBP),
      residues 68 to 88, induces an alpha beta + T cell population whose TCR beta
      chains are exclusively derived from the V beta 8 TCR gene family. As presented
      here, sequencing of these beta-chains has revealed the following. 1) There is an
      absolute restriction to a single V beta 8 family member, previously identified as
      V beta 8.2. This V region is used by only 10% of the V beta 8+ TCR found in
      normal unprimed mesenteric and cervical lymph node T cell populations. 2) There
      is a serine at residue 97 (in the CDR3 region of the beta-chain) which appears to
      be Ag-specific and is not found in normal populations of adult T cells. 3) There
      is a size restriction of these MBP-specific beta-chains, resulting from the
      addition and deletion of nucleotides in the CDR3 region, which tend to cancel
      each other out. 4) There is a paucity of N-region nucleotide additions in the J
      region of these MBP-specific beta-chains. Such a reduced number of nontemplate
      added nucleotides has been associated with receptors that rearrange early during
      development and fail to add nucleotides due to a lack of terminal
      deoxynucleotidyl transferase at that time. These results have led us to propose
      that the selection of MBP-reactive autoimmune T cells is based on both the Ag and
      the time frame when these cells are generated and enter the peripheral T cell
      pool.

PMID- 1370516
TI  - Expression of a monocyte chemotactic cytokine by human mononuclear phagocytes.
AB  - The present study was designed to investigate the capacity of human mononuclear
      phagocytes to produce a cytokine chemotactic for monocytes (monocyte chemotactic
      protein (MCP), alternative acronyms JE, monocyte chemotactic and activating
      factor, MCP-1, and tumor-derived chemotactic factor). Human PBMC exposed in vitro
      to bacterial LPS expressed high levels of MCP transcripts. Monocyte-depleted
      lymphoid cells were not induced to express MCP by LPS. Percoll-gradient purified
      monocytes were able to express high levels of MCP transcripts. In an effort to
      exclude a role of contaminating non-monocytic cells, mononuclear phagocytes were
      separated by flow cytometry and sorting: CD14+ cells exposed to LPS showed high
      levels of MCP mRNA. LPS-stimulated monocytes released chemotactic activity for
      monocytes that could be inhibited by absorption with anti-MCP antibodies. IL-1,
      TNF, IFN-gamma, granulocyte-macrophage-CSF and, to a lesser extent, macrophage
      CSF, as well as inactivated streptococci, also induced MCP gene expression.
      Actinomycin D experiments indicated that induction of MCP in monocytes was gene
      transcription-dependent. The protein synthesis inhibitor cycloheximide (Cy)
      blocked IL-1-, TNF-, or LPS-induced MCP gene expression in monocytes. In
      contrast, expression of the structurally related chemotactic cytokine IL-8 was
      superinduced by Cy. Moreover, Cy superinduced MCP gene expression in cells other
      than monocytes, including endothelial cells, smooth muscle cell and fibrosarcoma
      cells, indicating different mechanisms of regulation in mononuclear phagocytes vs
      cells of other lineages. The capacity of cells of the monocyte-macrophage lineage
      to produce a cytokine that recruits and activates circulating monocytes may be of
      considerable importance in inflammatory and immunologic reactions. Thus, the
      mononuclear phagocyte system can autonomously regulate the extravasation and
      activation of immature elements of the same lineage, a key event in inflammation
      and immunity.

PMID- 1370517
TI  - Effect of IL-3 and stem cell factor on the appearance of human basophils and mast
      cells from CD34+ pluripotent progenitor cells.
AB  - Hemopoietic stem cell factor (SCF), which is the ligand for the proto-oncogene c
      kit receptor (allelic with W locus) and the product of Sl locus of the mouse, has
      recently been cloned. The human homologue has also been cloned, and recombinant
      protein (human rSCF) expressed and purified to homogeneity. To determine the
      effect of human rSCF in the presence or absence of human rIL-3 on human bone
      marrow-derived mast cells and basophils, human CD34+ pluripotent progenitor
      cells, highly enriched (greater than 99%) from bone marrow mononuclear cells,
      were cultured over agarose surfaces (interphase cultures) in the presence of
      human rIL-3, human rIL-3 and increasing concentrations of human rSCF, or human
      rSCF alone. Over 3 to 4 wk, human rSCF acted synergistically with human rIL-3 at
      all concentrations, producing a three- to fivefold increase in total, mast cell,
      and basophil numbers over human rIL-3 alone when used at 100 ng/ml. The
      percentage of cell types in the human rIL-3 and human rIL-3 plus human rSCF
      cultures, however, remained the same, with basophils constituting 18 to 35% of
      the final cultured cells, and mast cells 3% or less of the final cell number. In
      the presence of human rSCF alone, the combined total percentage of mast cells and
      basophils was 0 to 1.0%, the majority of cells being macrophages. Mast cells
      cultured in human rIL-3 plus human rSCF, but not human rIL-3 alone, were
      berberine sulfate positive, suggesting the presence of heparin proteoglycans
      within granules. Electron microscopic examination of cultures supplemented with
      human rIL-3 and rSCF, but not human rIL-3 alone, revealed that after 3 wk in
      culture, mast cell granules contained tryptase and exhibited scroll, reticular,
      and homogeneous patterns as seen previously in CD34+/3T3 fibroblast cocultures.
      Thus, CD34+ cells cultured in the presence of both human rIL-3 and rSCF give rise
      to cultures containing increased numbers of basophils and mast cells, with the
      mast cells by ultrastructural studies showing evidence of maturation although the
      percentages of basophils and mast cells arising in these cultures remained
      unchanged.

PMID- 1370519
TI  - A "network antigen" for human CD4. A murine monoclonal anti-idiotype to Leu-3a
      induces an anti-CD4 response in naive mice.
AB  - Previous studies have evaluated anti-CD4 mAb as idiotypic models of the HIV gp120
      binding site for CD4. The success of this strategy depends upon the concept of
      internal image, whereby the binding paratope of the anti-CD4 structurally mimics
      the equivalent binding surface on HIV gp120. To test this concept of internal
      image, anti-idiotypic antibodies were raised against the anti-CD4, Leu-3a. If any
      of these anti-Id detect the paratopic idiotope on the anti-CD4 antibody, their
      own respective paratopes should structurally model the corresponding binding
      epitope on CD4 bound by Leu-3a. Consequently, the immunization of naive mice with
      the selected anti-Id should induce an anti-CD4 response which reflects the
      binding specificities of Leu-3a. Four anti-Id to Leu-3a were characterized and
      tested for their ability to induce anti-CD4 responses in naive animals. Although
      one anti-Id induced an anti-CD4 response in mice, no such response could be
      detected in other species. Thus the failure to raise anti-Id with internal image
      characteristics may provide an explanation for the lack of anti-gp120 activity
      reported in anti-Id antisera raised to multiple anti-CD4 antibodies.

PMID- 1370518
TI  - Relationship between cytokine-dependent cell cycle progression and MHC class II
      antigen expression by human CD34+ HLA-DR- bone marrow cells.
AB  - Human CD34+ HLA-DR- bone marrow cells constitute a phenotypically homogeneous
      population of quiescent cells. More than 97% of CD34+ HLA-DR- cells reside in the
      G0/G1 phase of the cell cycle. The in vitro effects of two cytokines, IL-1 alpha
      and IL-3, alone or in combination, on the viability, cell cycle status and
      acquisition of HLA-DR by this cell population were examined. Cell viability was
      preserved in cultures receiving cytokines, but declined steadily in cultures
      deprived of exogenous IL. Over a period of 4 days, IL-3 progressively induced the
      expression of HLA-DR although driving corresponding numbers of cells into S and
      G2 + M. Although IL-1 alpha induced the expression of HLA-DR, it was not as
      effective as IL-3 in promoting the exit of these cells from G0/G1. Combinations
      of IL-1 alpha and IL-3, however, exerted an even greater effect on promoting both
      HLA-DR expression and entry of cells into active phases of the cell cycle.
      Simultaneous measurement of HLA-DR expression and cell cycle status in response
      to IL-1 alpha and IL-3 indicated that the majority of de novo expression of HLA
      DR occurred in cells that remained in G0/G1. CD34+ HLA-DR- cells cultured with IL
      1 alpha and IL-3 but arrested in G0/G1 by hydroxyurea were still capable of
      expressing HLA-DR, demonstrating that the acquisition of HLA-DR was independent
      of the entry of these cells into active phases of the cell cycle. These data
      indicate that the survival, HLA-DR expression, and cell cycle status of human
      CD34+ HLA-DR- bone marrow cells are governed by regulatory cytokines such as IL-1
      alpha and IL-3. In addition, the entry of these cells into active phases of the
      cell cycle does not seem to be a prerequisite for the expression of HLA-DR, nor
      does it seem that the acquisition of HLA-DR by hematopoietic progenitor cells is
      a marker of cells entering the S phase of the cell cycle.

PMID- 1370520
TI  - CD66 monoclonal antibodies recognize a phosphotyrosine-containing protein bearing
      a carcinoembryonic antigen cross-reacting antigen on the surface of human
      neutrophils.
AB  - The CD66 Ag is a neutrophil-specific "activation Ag" in that it is detected in
      low density on resting cells but its surface expression is up-regulated by
      stimulation (with the chemotactic peptide FMLP, the calcium ionophore A23187, and
      12-O-tetradeconoyl-phorbol-13-acetate). Phosphorylation is an important mechanism
      of regulation of protein function. Although most studies of protein
      phosphorylation have focused on intracellular reactions, recent studies have
      provided evidence for the existence of ectoprotein kinase activity on the surface
      of several types of cells including human neutrophils. The role of ectoprotein
      kinase activity in cell function is unknown and little is known about the
      endogenous substrates of this enzyme system. The identification and
      characterization of physiologic substrates of ectoprotein kinase activity should
      aid the understanding of the role of this enzyme activity in cell function.
      Immunoprecipitation and subsequent gel electrophoresis of proteins from
      neutrophils labeled with [gamma-32P]ATP revealed that CD66 mAb specifically
      recognize a approximately 180-kDa phosphoprotein on the surface of human
      neutrophils. This protein was one of the major endogenous substrates for human
      neutrophil ectoprotein kinase activity. Phosphoamino acid analysis of the 180-kDa
      protein revealed that it contained predominantly phosphotyrosine. Preclearing
      studies demonstrated that this protein was also recognized by CD15 mAb, and by
      polyclonal anticarcinoembryonic Ag antiserum. In addition, the CD66 mAb reacted
      with purified carcinoembryonic Ag, biliary glycoprotein, and "nonspecific cross
      reacting Ag." Thus, the neutrophil protein recognized by CD66 mAb appears to be a
      approximately 180-kDa form of the classical "nonspecific cross-reacting Ag" on
      human neutrophils.

PMID- 1370521
TI  - Epitopes of group A streptococcal M protein that evoke cross-protective local
      immune responses.
AB  - The present studies were undertaken to identify conserved epitopes of group A
      streptococcal M proteins that evoke cross-protective mucosal immune responses.
      Two synthetic peptides copying conserved regions of type 5 M protein, designated
      SM5(235-264)C and SM5(265-291)C, were covalently linked to carrier molecules and
      their immunogenicity was tested in laboratory animals. Rabbit antisera against
      both peptides cross-reacted with multiple serotypes of group A streptococci,
      indicating that the peptides contained broadly cross-reactive, surface exposed M
      protein epitopes. Serum antipeptide antibodies adsorbed to the surface of
      heterologous type 24 streptococci passively protected mice against intranasal
      challenge infections. Mice that were actively immunized intranasally with each
      synthetic peptide covalently linked to the B subunit of cholera toxin were
      protected against colonization and death after intranasal challenge infections
      with type 24 streptococci in the absence of serum opsonic antibodies. These data
      confirm and extend previous observations that conserved M protein epitopes evoke
      cross-protective local immunity and may serve as the basis for broadly cross
      protective M protein vaccines.

PMID- 1370522
TI  - Overlapping epitopes that are recognized by CD8+ HLA class I-restricted and CD4+
      class II-restricted cytotoxic T lymphocytes are contained within an influenza
      nucleoprotein peptide.
AB  - Viral epitopes that are recognized by both HLA class I-restricted and class II
      restricted T cells have been defined for a type A influenza virus nucleoprotein
      (NP) peptide. CD8+ and CD4+ CTL lines have been generated against a synthetic
      peptide encompassing residues 335 to 349 of NP that are restricted by HLA-B37 and
      HLA-DQw5, respectively. Both of these CTL populations were capable of
      specifically lysing influenza A virus-infected targets, indicating that a
      naturally processed NP peptide(s) was being mimicked by the NP (335-349) peptide.
      Amino acid residues that are critical for recognition of this NP determinant in
      the context of HLA-B37 and HLA-DQw5 were investigated by the use of panels of
      truncated and alanine-substituted NP peptides. The results demonstrate that: 1)
      truncations in the amino- or carboxy-terminal ends differentially affect CD8+ and
      CD4+ CTL recognition; 2) the NP (335-349) sequence contains two octapeptide
      epitopes that share a core of six amino acid residues (NP 338-343); and 3)
      alanine substitutions at five of these residues abrogated recognition by at least
      one of the CD8+ and CD4+ CTL lines. Thus, these class I- and class II-restricted
      CTL lines recognize similar but distinct epitopes, and different structural
      features of the NP peptide are required for presentation by HLA-B37 and HLA-DQw5.
      Comparison of the amino acid sequences of the NP peptide presented by HLA-B37 and
      HLA-DQw5 with other peptides known to be presented by both class I and class II
      molecules revealed a common motif among these peptides.

PMID- 1370523
TI  - Promiscuous malaria peptide epitope stimulates CD45Ra T cells from peripheral
      blood of nonexposed donors.
AB  - PBL from individuals with no history of malaria exposure, as well as cord blood
      lymphocytes, were tested for proliferation to T cell epitopes from the malaria
      circumsporozoite proteins of Plasmodium falciparum and Plasmodium vivax. Cells
      from many individuals proliferated in response to these peptides, but for two
      peptides (P. vivax317-336 and P. falciparum CS331-350) the response rate ranged
      from 64 to 93%, with the specific stimulation indices reaching as high as 38. The
      phenotype of the cells responding to PfCS331-350 was predominantly CD4+,CD8
      ,CD45Ra+,CD45Ro-, which was the inverse of the phenotype of the cells responding
      to tetanus toxoid with respect to CD45 isoforms. T cell clones from different
      individuals specific for PfCS331-350 were restricted by at least four different
      HLA-DR molecules and there was no evidence that the peptide was a "superantigen."
      Overlapping peptides were used to demonstrate that clones had different fine
      specificities although the peptide specificities of the DR4-restricted and DR11
      restricted clones were similar. Although the individuals tested here have had no
      history of malaria exposure, these data demonstrate that they have T cells
      specific for malaria sequences present in high frequency that proliferate as
      intensely as some memory responses. Although one clone from an individual with a
      history of BCG vaccination did react strongly with PPD, the phenotype of these
      cells suggests that they are not classical memory cells for a cross-reactive
      recall Ag. Such cells may affect the induction or expression of malaria immunity.

PMID- 1370524
TI  - A chemically defined synthetic vaccine model for HIV-1.
AB  - Multiple Ag peptide (MAP) system without the use of a protein carrier was used as
      a vaccine model in three species of animals. Synthetic peptides from the V3
      region of the gp120 of IIIB, RF and MN HIV-1 isolates were used as the Ag. MAP
      consisting of various chain lengths, from 11 to 24 residues, were prepared in a
      monoepitope configuration containing four repeats of each individual peptide. In
      parallel, they were synthesized in a diepitope configuration adding at the
      carboxyl-terminus of the V3 peptides a conserved sequence, known to be a Th cell
      epitope of gp120. The antibody response elicited by the monoepitope constructs
      was species-dependent. Rabbits produced immunity against all nine peptides,
      whereas mice were strongly reactive mainly to the longest sequence of the IIIB
      isolate. The immune response of guinea pigs was intermediate to those of rabbits
      and mice. Diepitope MAPs were immunogenic in all three species and elicited
      significantly higher titers than those raised by the immunization with the
      monoepitope MAPs. The response was type specific; the high-titered antibodies
      were reactive mostly against the isolate from which the peptides were derived,
      with a small cross-reactivity in ELISA between IIIB and RF strains. The dominant
      antigenic site of the B cell epitope, IIIB sequence, was located at the amino and
      central part of the MAP and a sequence overlapping the putative V3 reverse-turn
      was particularly reactive with the raised antibodies. Moreover, sera from the
      immunized animals inhibited virus-dependent cell fusion. These results show that
      MAP, with a chemically defined structure and without the use of a protein
      carrier, can be potentially useful for the design of synthetic HIV-1 vaccine
      candidates.

PMID- 1370525
TI  - Geographic diversity of human immunodeficiency virus type 1: serologic reactivity
      to env epitopes and relationship to neutralization.
AB  - The antibody recognition of the major neutralization epitopes of human
      immunodeficiency virus type 1 (HIV-1) in 829 HIV-1-seropositive subjects from
      North America (106), Europe (241), Africa (342), and Asia (100) was investigated.
      Peptides derived from diverse published V3 loop sequences were used as antigen,
      and serum reactivity was detected by sensitive ELISAs. Antibody binding to
      peptides derived from the V3 loop sequence of HIV-1 isolates varies considerably
      depending on the geographic origin of the antibody and is associated with
      neutralization titer against homologous isolates. Serotype reactivity to peptides
      may be a simple and rapid approach to investigation of HIV-1 env diversity
      worldwide and may assist the choice of immunogen for development of future AIDS
      vaccines.

PMID- 1370526
TI  - Segregation of human T cell lymphotropic virus type I and II infections by
      antibody reactivity to unique viral epitopes.
AB  - A recombinant protein of the human T cell lymphotropic virus type I (HTLV-I) gp46
      outer membrane envelope, MTA-4 (residues 129-203), reacted by Western blot with
      sera from HTLV-I-infected individuals from the United States and Jamaica but not
      with 24 (10%) of 242 Japanese sera. A related gp46 recombinant protein, MTA-1
      (residues 162-209), reacted with all 58 sera from HTLV-I-infected US and Jamaican
      individuals and 238 of 242 sera from infected Japanese (combined sensitivity of
      99%). Neither recombinant showed reactivity to sera from HTLV-II-infected
      individuals or uninfected controls. The reactivity of recombinant proteins
      containing the region of HTLV-II gp46 analogous to MTA-1 was also evaluated by
      Western blot: GH2-K15 (residues 157-205) and GH2-K55 (residues 162-205) reacted
      with 88 (98%) and 89 (99%), respectively, of 90 sera from HTLV-II-infected
      individuals but not with sera from HTLV-I-infected individuals or uninfected
      controls. These recombinant proteins should permit the development of assays to
      unambiguously confirm and differentiate HTLV-I and HTLV-II infections.

PMID- 1370527
TI  - Antigen-pulsed dendritic cells can efficiently induce an antibody response in
      vivo.
AB  - The aim of this study was to develop an immunization procedure avoiding external
      adjuvant. Data are presented showing that syngeneic dendritic cells (DC), which
      have been pulsed in vitro with antigen, induce a strong antibody response in
      mice. By contrast, antigen (Ag)-pulsed low-density B cells, although equally able
      to induce interleukin 2 secretion by an Ag-specific T cell hybridoma in vitro,
      only weakly prime the mice in vivo. Moreover, we show that the injection of Ag
      pulsed DC induces the synthesis of isotypes similar to the immunoglobulin classes
      detected after immunization with the same Ag in complete Freund's adjuvant.
      Importantly, high amounts of IgG2a antibodies are produced, suggesting that T
      helper type 1 cells are activated. Collectively, these data indicate that DC can
      initiate a primary humoral response and that they may be used as physiological
      adjuvant in vivo.

PMID- 1370528
TI  - Immunogenicity of a chimeric peptide corresponding to T helper and B cell
      epitopes of the Chlamydia trachomatis major outer membrane protein.
AB  - The immunogenicity of a chimeric T/B cell peptide corresponding to antigenically
      characterized epitopes of the Chlamydia trachomatis major outer membrane protein
      (MOMP) was studied in mice to further define its potential use in the development
      of a subunit vaccine in preventing blinding trachoma in humans. The chimeric
      peptide, designated A8-VDI, corresponds to a conserved MOMP T helper (Th) cell
      epitope(s) (A8, residues 106-130) and serovar A VDI (residues 66-80), which
      contains the serovar-specific neutralizing epitope 71VAGLEK76. Mice immunized
      with peptide A8-VDI produced high-titered polyclonal IgG antibodies which
      recognized the VAGLEK-neutralizing epitope. Peptide A8-VDI primed A/J mice to
      produce high-titered serum-neutralizing antibodies in response to a secondary
      immunization with intact chlamydial elementary bodies (EBs). Peptide A8-VDI, but
      not peptide VDI alone, was immunogenic in six different inbred strains of mice
      disparate at H-2, indicating that the Th cell epitope(s) contained in the A8
      portion of the chimera was recognized in the context of multiple major
      histocompatibility complex (MHC) haplotypes. An unexpected finding of this work
      was that different inbred strains of mice immunized with the chimeric peptide
      produced antibodies of differing fine specificities to the VDI portion of the
      chimera. Some mouse strains produced anti-VDI antibodies that did not recognize
      the VAGLEK-neutralizing epitope. The ability of mice to respond to the VAGLEK
      neutralizing site was not dependent on MHC haplotype since mouse strains of the
      same H-2 haplotype produced anti-VDI antibodies of differing fine specificity.

PMID- 1370529
TI  - c-kit ligand: a unique potentiator of mediator release by human lung mast cells.
AB  - Mast cells (MC) play a central role in extrinsic allergic reactions such as
      asthma and may participate in other inflammatory and fibrotic processes. However,
      with the exception of immunoglobulin E (IgE) receptor-dependent stimulation, no
      secretagogues of human lung MC have yet been described. It is also unclear
      whether mediator release can be regulated by certain cytokines as demonstrated
      previously in basophils and other human inflammatory effector cells. Here, we
      show that the c-kit ligand (KL), a recently identified stem cell growth factor,
      at concentrations 10-100 times lower than that required to promote cell
      proliferation, enhances the release of histamine and leukotriene C4 in response
      to IgE receptor crosslinking of human lung MC. KL does not induce mediator
      release per se, but increases the sensitivity of MC to anti-IgE receptor
      stimulation and also enhances mediator release to maximally effective
      concentrations of anti-IgE receptor antibody. By contrast, a large number of
      cytokines examined, including the mast cell growth factors/agonists in rodents,
      interleukin 3 (IL-3), IL-4, IL-9, and nerve growth factor, were ineffective in
      this respect. These findings suggest a unique role of KL in regulating effector
      functions of human mucosal MC.

PMID- 1370530
TI  - The rat c-kit ligand, stem cell factor, induces c-kit receptor-dependent mouse
      mast cell activation in vivo. Evidence that signaling through the c-kit receptor
      can induce expression of cellular function.
AB  - Interactions between products of the mouse W locus, which encodes the c-kit
      tyrosine kinase receptor, and the Sl locus, which encodes a ligand for c-kit
      receptor, which we have designated stem cell factor (SCF), have a critical role
      in the development of mast cells. Mice homozygous for mutations at either locus
      exhibit several phenotypic abnormalities including a virtual absence of mast
      cells. Moreover, the c-kit ligand SCF can induce the proliferation and maturation
      of normal mast cells in vitro or in vivo, and also can result in repair of the
      mast cell deficiency of Sl/Sld mice in vivo. We now report that administration of
      SCF intradermally in vivo results in dermal mast cell activation and a mast cell
      dependent acute inflammatory response. This effect is c-kit receptor dependent,
      in that it is not observed when SCF is administered to mice containing dermal
      mast cells expressing functionally inactive c-kit receptors, is observed with
      both glycosylated and nonglycosylated forms of SCF, and occurs at doses of SCF at
      least 10-fold lower on a molar basis than the minimally effective dose of the
      classical dermal mast cell-activating agent substance P. These findings represent
      the first demonstration in vivo that a c-kit ligand can result in the functional
      activation of any cellular lineage expressing the c-kit receptor, and suggest
      that interactions between the c-kit receptor and its ligand may influence mast
      cell biology through complex effects on proliferation, maturation, and function.

PMID- 1370531
TI  - Phospholipase C-gamma 1 association with CD3 structure in T cells.
AB  - Recently, we and others have reported tyrosine phosphorylation of phospholipase C
      gamma 1 (PLC gamma 1) enzyme after CD3 activation of T cells, and have proposed
      that PLC gamma 1 mediates signal transduction through the T cell receptor
      (TCR/CD3). Here, using immunoblotting and immune complex PLC assays, we show that
      CD3 stimulation of Jurkat cells induces the association of PLC gamma 1 enzyme
      with CD3 complex. PLC activity is also found to co-precipitate with the CD3 zeta
      chain from activated cells. In addition, in vitro PLC assays show that CD3
      activation leads to about 10-fold stimulation of PLC gamma 1 activity. These
      results, along with the observation that Jurkat cells preferentially express PLC
      gamma 1, indicate that PLC gamma 1 participates in CD3 signaling.

PMID- 1370532
TI  - Molecular analysis of the induction of immunoglobulin E synthesis in human B
      cells by interleukin 4 and engagement of CD40 antigen.
AB  - The molecular events leading to immunoglobulin E (IgE) synthesis in human sIgE- B
      cells stimulated with interleukin 4 (IL-4) and anti-CD40 monoclonal antibody
      (mAb) 626.1 were analyzed. Anti-CD40 mAb increased the levels of IL-4-induced
      germline C epsilon transcripts and induced the production of mature C epsilon
      mRNA. These effects were dependent on the presence of IL-4. Nested primer PCR
      revealed deletional switch recombination occurring only in B cell stimulated with
      both IL-4 and anti-CD40 mAb. DNA sequence analysis of switch fragments showed
      direct S mu/S epsilon joining, without the deletions or duplications within S mu
      often found in B cells stimulated with IL-4 and Epstein-Barr virus. Analysis of
      the switch junction map sites showed "hot spots" for recombination within S mu,
      but not within S epsilon. These findings indicate that IL-4 provides a signal to
      B cells to induce germline C epsilon transcription and concurrent CD40 engagement
      induces S mu/S epsilon deletional switch recombination, production of mature C
      epsilon mRNA, and IgE synthesis.

PMID- 1370533
TI  - The injection of deaggregated gamma globulins in adult mice induces antigen
      specific unresponsiveness of T helper type 1 but not type 2 lymphocytes.
AB  - Injection of adult mice with high doses of monomeric human gamma globulins (dHGG)
      has been previously shown to produce a state of peripheral tolerance in both B
      and T cells. To gain insight into the mechanism of induction and maintenance of
      adult tolerance in this model, we have analyzed the pattern of lymphokines
      produced by control and tolerant animals in response to the tolerogen. The data
      presented indicate that HGG-specific, interleukin 2 (IL-2)- and interferon gamma
      (IFN-gamma)-producing T cells (thus referred to as T helper type 1 [Th1] cells)
      are rendered unresponsive after in vivo administration of soluble HGG. In
      contrast, antigenic stimulation of T cells isolated from tolerant adult mice
      leads to increased production of IL-4 in vitro. In vivo challenge of dHGG-treated
      adult animals with hapten-coupled HGG (p-azophenylarsonate [ARS]-HGG) induced a
      significant ARS-specific antibody response, suggesting that tolerance induction
      in this model does not completely abrogate tolerogen-specific Th activity in
      vivo. In agreement with the in vitro data, hapten-specific antibody response of
      tolerant animals is characterized by a selective deficiency in the IFN-gamma
      dependent IgG2a subclass. Injection of immunogenic forms of HGG into tolerant
      animals also produced an IL-4-dependent increase in total serum IgE levels,
      indicative of an increased activity of HGG-specific Th2 cells in these animals.
      The finding that tolerance induction differentially affects Th subpopulations
      suggests that crossregulation among lymphocyte subsets may play a role in the
      induction and/or maintenance of acquired tolerance in adults.

PMID- 1370534
TI  - Generation of a subtype-specific neutralization epitope in foot-and-mouth disease
      virus of a different subtype.
AB  - An epitope involved in neutralization of foot-and-mouth disease virus (FMDV) of
      subtype C3 was generated by a single amino acid replacement in VP1 of FMDV of
      subtype C1. The replacement [Ser (139)----Ile, in the immunodominant site A] was
      consistently found in those FMDV C1 Santa Pau-Sp/70 mutants resistant to
      neutralization by monoclonal antibody (MAb) SD6 (specific for most C1 viruses)
      that acquired the capacity to be neutralized by MAb 7AB5 (specific for C3
      viruses).

PMID- 1370535
TI  - Mitochondrial encephalomyopathies with the mutation of the mitochondrial
      tRNA(Leu(UUR)) gene.
AB  - Four families with mitochondrial encephalomyopathy are described. Probands of
      three families had typical clinical presentations of mitochondrial myopathy,
      encephalopathy, lactic acidosis, and strokelike episodes (MELAS), but the proband
      of family 4 lacked strokelike episodes. The mitochondrial DNA mutation of
      tRNA(Leu(UUR)) (transfer ribonucleic acid specific to leucine (UUR codon)) found
      in MELAS was examined in muscle DNA obtained from biopsy samples of the probands
      of four families and the maternal relatives of family 2. The mutation was
      detected in all muscle samples, and the degree of the mutated DNA was 68% to 84%
      by Southern blot analysis. However, the clinical patterns of the maternal
      relatives of family 2 were mild and distinctly different from MELAS. The same
      mutation was also detected in blood-derived DNA samples of all family members
      examined, including healthy mothers but not fathers, although the degree of
      mutation did not correlate with the clinical severity. These results confirmed
      the maternal inheritance of this disease and suggested that the mitochondrial DNA
      mutation (tRNA(Leu(UUR))) may cause clinical symptoms other than MELAS. The
      clinical findings of mitochondrial encephalomyopathy should be reinvestigated in
      terms of the mitochondrial gene mutation; the polymerase chain reaction method
      will be useful for screening for this mutation of mitochondrial DNA in blood
      samples.

PMID- 1370536
TI  - Local immune response in patients with cow milk allergy: follow-up of patients
      retaining allergy or becoming tolerant.
AB  - To assist in identifying factors that determine the clinical outcome of cow milk
      allergy, we subjected to rechallenge 37 patients with a history of cow milk
      allergy, mean (+/- SD) age 27.6 +/- 7.1 months, after a follow-up of 13.5 +/- 5.1
      months with a milk-free diet. A solid-phase enzyme-linked immunoassay was used to
      assess the total number of immunoglobulin-secreting and specific antibody
      secreting cells among peripheral blood lymphocytes primed during provocation by
      milk antigens, giving indirect evidence of local immune response in the gut.
      Patients with persistent cow milk allergy (n = 13) had milder reactions at
      rechallenge than they had shown at the time of diagnosis. Numbers of
      immunoglobulin-secreting cells in these patients increased significantly from a
      geometric mean (95% confidence interval) in the IgA class of 1570 (1009, 2445) to
      2984 (1941, 4583) IgA-secreting cells/10(6) cells, in the IgG class of 1445
      (1067, 1959) to 2740 (1698, 4425) IgG-secreting cells/10(6) cells, and in the IgM
      class of 842 (534, 1325) to 2235 (1429, 3495) IgM-secreting cells/10(6) cells. By
      contrast, in patients (n = 24) who had acquired cow milk tolerance, the number of
      immunoglobulin-secreting cells did not increase during provocation. The total
      number of IgA-secreting cells before rechallenge was significantly higher than it
      had been before the initial challenge. The patients who acquired cow milk
      tolerance also had specific antibody-secreting cells of IgA isotype before the
      second challenge. These results indicate that in cow milk allergy the ability to
      mount a local immune response against cow milk antigens, particularly in the IgA
      class, is related to the suppression of clinical sensitivity.

PMID- 1370537
TI  - Antagonists of nitric oxide synthesis inhibit nerve-mediated relaxations of
      longitudinal muscle in guinea pig ileum.
AB  - Enteric inhibitory nerves release nonadrenergic, noncholinergic (NANC)
      transmitters onto the muscle layers of guinea pig ileum. Nitric oxide (NO),
      released from endothelial cells, relaxes vascular smooth muscle and NO may also
      be a chemical messenger released from neurons. The present study investigated the
      possibility that NO is a NANC transmitter in guinea pig ileum longitudinal muscle
      myenteric plexus. Segments of longitudinal muscle myenteric plexus were
      maintained in scopolamine-containing (1 microM) Krebs' solution. Histamine (1
      microM) was used to induce tone, and NANC relaxations were produced by trains of
      transmural electrical stimuli. NANC responses consisted of a fast relaxation
      (approximately 1 s duration) followed either by a slow relaxation or a slow
      contraction (approximately 4 s duration). The NO-synthase inhibitors, NG
      monomethyl-L-arginine, NG-nitro-L-arginine and NG-nitro-L-arginine methyl ester,
      inhibited peak (fast) neurogenic relaxations by a maximum of 62 +/- 6%, 91 +/- 3%
      and 50 +/- 3%, respectively. NO-synthase inhibitors either completely blocked the
      slow relaxation revealing a late contraction or increased the amplitude of late
      contractions. The actions of NG-monomethyl-L-arginine were partially reversed by
      L-arginine (1 mM) while the actions of NG-nitro-L-arginine methyl ester and NG
      nitro-L-arginine were not consistently reversed by L-arginine. L-Arginine itself
      did not alter neurogenic responses. NG-monomethyl-D-arginine (10-300 microM) did
      not affect NANC relaxations or contractions. Hemoglobin (10 microM) inhibited
      peak NANC relaxations by 45 +/- 4% and increased the amplitude of late
      contractions without affecting papaverine-induced relaxations. Sodium
      nitroprusside and 8-bromo-cyclic guanosine monophosphate mimicked NANC
      relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370538
TI  - Pharmacological profile of the new potent neuroleptic ocaperidone (R 79,598).
AB  - Ocaperidone, a new benzisoxazolyl piperidine neuroleptic, was compared with
      haloperidol, risperidone and ritanserin in a large series of pharmacological
      tests. Ocaperidone inhibited dopamine agonist (apomorphine, amphetamine or
      cocaine)-induced behavioral effects at low doses (0.014-0.042 mg/kg) and was,
      thereby, equipotent with haloperidol (0.016-0.024 mg/kg) and 2.0 to 8.3 times
      more potent than risperidone. Ocaperidone completely blocked the dopamine agonist
      behavior at slightly higher doses (0.064 mg/kg) and was, thereby, more potent and
      efficacious than haloperidol (0.097-0.13 mg/kg) and risperidone (0.59-1.17
      mg/kg). The dissociation between inhibition of apomorphine behavior and induction
      of catalepsy was as high for ocaperidone (22) as for risperidone (20) and higher
      than for haloperidol (8), suggesting risperidone-like low extrapyramidal side
      effect liability. Ocaperidone also antagonized serotonin agonist (tryptamine,
      mescaline or 5-hydroxytryptophan)-induced behavioral effects (0.011-0.064 mg/kg)
      and was, thereby, equipotent with risperidone (0.014-0.056 mg/kg) and at least as
      potent as ritanserin (0.037-0.13 mg/kg). Ocaperidone displayed its serotonin and
      dopamine antagonism at the same dose levels, in contrast to risperidone, which
      was a predominant serotonin antagonist. Apart from protection from compound 48/80
      lethality (0.042 mg/kg) and norepinephrine lethality (0.097 mg/kg), which were
      not considered to hinder its clinical application, no additional secondary
      effects were observed at low doses of ocaperidone. In the apomorphine test in
      dogs, ocaperidone was very potent (i.v., s.c. and p.o. ED50 values: less than 1.0
      micrograms/kg) and showed a rapid onset (less than 0.5 h) and long duration of
      action (24 h) after p.o. administration. Ocaperidone is concluded to be a highly
      potent and efficacious dopamine-D2 antagonist with concomitant, equivalent
      serotonin 5-HT2 antagonism. Ocaperidone is expected to exert pronounced
      haloperidol-like effects on the positive symptoms of schizophrenic patients but
      with risperidone-like low extrapyramidal side effect liability and improved
      patient compliance.

PMID- 1370539
TI  - Behavioral disinhibition and depression in amphetaminized rats: a comparison of
      risperidone, ocaperidone and haloperidol.
AB  - The mixed serotonin-2/dopamine-D2 antagonists risperidone and ocaperidone were
      compared with the specific D2 antagonist haloperidol for their ability to
      antagonize amphetamine (10 mg/kg, s.c.)-induced stereotypy in rats. Four
      successive stages of amphetamine antagonism were differentiated: 1)
      disinhibition: reversal of stationary stereotypy into the hyperactivity normally
      observed with lower doses of amphetamine; 2) inhibition: the first significant
      reduction of activity; 3) normalization: reduction of activity to the level of
      nonamphetaminized rats; and 4) suppression: reduction of activity to 50% of the
      level of nonamphetaminized rats. Ocaperidone and risperidone were equipotent with
      haloperidol for disinhibition (0.0062-0.011 mg/kg). However, the disinhibition
      was maintained over a wider dose range with risperidone (factor 84) than with
      haloperidol (9.0) and ocaperidone (4.1) and was also more pronounced in magnitude
      with risperidone. Ocaperidone was equipotent with haloperidol for inhibition
      (0.013-0.025 mg/kg) and normalization (0.074-0.080 mg/kg) but 4.4 times less
      potent for suppression of activity (0.71 vs. 0.16 mg/kg). Risperidone became
      progressively less potent than haloperidol: 4.4 times for inhibition, 9.6 times
      for normalization and 22 times for suppression of activity. The present data are
      consistent with the hypothesis that serotonin-2 antagonism compensates for the
      functional consequences of D2 receptor blockade. The implications for the
      clinical application of the compounds are discussed.

PMID- 1370541
TI  - N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal
      norepinephrine release. II. Evidence for functional cooperation and for
      coexistence on the same axon terminal.
AB  - The possible interactions between activation of N-methyl-D-aspartic acid (NMDA)
      receptors and non-NMDA receptors regulating the release of [3H]norepinephrine [(
      3H]NE) have been investigated in superfused synaptosomes from rat hippocampus.
      NMDA--at a concentration (100 microM) which, in a medium containing 1.2 mM Mg++
      ions, did not evoke [3H]NE release--acquired releasing activity in the presence
      of equimolar concentrations of quisqualic acid (QA), (RS)-alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) or kainic acid. The [3H] NE release
      evoked by NMDA plus QA in the presence of Mg++ ions was Ca(++)-dependent, partly
      tetrodotoxin-sensitive, inhibited by clonidine but insensitive to desipramine.
      The NMDA receptor antagonists D-2-amino-5-phosphonopentanoic acid (D-AP5) and (+)
      5-methyl-10,11-dihydro-5-H-dibenzo[a,d]cycloepten-5,10-imine (MK-801) antagonized
      the NMDA-induced [3H]NE release in Mg(++)-free medium; the IC50 values amounted,
      respectively, to 81.4 microM and to 1.11 microM. When NMDA was tested in the
      presence of QA and Mg++ ions, the affinity of D-AP5 was enormously increased
      (IC50 = 40 nM; i.e., more than 6 orders of magnitude); the affinity of MK-801 was
      found to be augmented by 350-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370540
TI  - N-methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal
      norepinephrine release. I. Location on axon terminals and pharmacological
      characterization.
AB  - The effects of endogenous and exogenous agonists at excitatory amino acid
      receptors mediating enhancement of [3H]norepinephrine [( 3H]NE) release have been
      investigated using superfused rat hippocampal synaptosomes. In Mg(++)-free medium
      L-glutamic acid (L-Glu), L-aspartic acid (L-Asp), N-methyl-D-aspartic acid
      (NMDA), kainic acid, (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) and quisqualic acid (QA) all increased the release of [3H]NE. L-Glu
      produced the largest effect. In the presence of Mg++ (1.2 mM), the effect of L
      Glu decreased by about 40%; L-Asp and NMDA lost completely their activity while
      the effects of kainic acid, QA and AMPA did not change significantly. Similarly
      to NMDA, the effect of L-Asp was augmented by glycine and blocked by NMDA
      receptor antagonists, while it was insensitive to the non-NMDA receptor
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The effect of L-Glu on
      [3H] NE release was partly decreased by the NMDA receptor channel blocker (+)-5
      methyl-10,11-dihydro-5-H-dibenzo[a,d]cycloepten-5,10-imine (MK-801) and partly by
      CNQX; when present together, the two antagonists completely abolished the L-Glu
      effect. The QA enhancement of [3H]NE release was antagonized by CNQX but it was
      insensitive to other classical non-NMDA receptor antagonists. IN CONCLUSION: 1)
      release-enhancing NMDA and non-NMDA receptors exist on noradrenergic axon
      terminals of rat hippocampus; 2) L-Asp appears to be a potent selective NMDA
      receptor agonist while L-Glu can activate also non-NMDA receptors; 3) the NE
      releasing receptor activated by QA may represent a QA/AMPA receptor subtype.

PMID- 1370542
TI  - Comparison of Clostridium sordellii toxins HT and LT with toxins A and B of C.
      difficile.
AB  - Clostridium sordellii produces two toxins, designated HT (haemorrhagic toxin) and
      LT (lethal toxin), that are similar to toxins A and B of C. difficile. The
      physicochemical properties of toxins HT and A were remarkably similar. The
      specific biological activities of toxin HT were almost the same as those of toxin
      A, and their NH2-terminal sequences shared close homology. The properties of
      toxins LT and B were similar, as were their NH2-terminal sequences, but toxin B
      was much more cytotoxic than toxin LT. Immunodiffusion analysis with specific
      antibodies showed that although toxins B and LT shared major antigenic
      determinants, each had unique epitopes. The results suggest that toxins B and LT
      have diverged more than toxins A and HT. Immunoblotting with antibodies to the
      toxins of C. difficile showed that toxins HT and LT had common antigenic
      determinants.

PMID- 1370543
TI  - Substructure of the flagellar basal body of Salmonella typhimurium.
AB  - The Salmonella typhimurium basal body, a part of the flagellar rotary motor,
      consists of four rings (denoted M, S, P and L) and a coaxial rod. Using low-dose
      electron microscopy and image averaging methods on negatively stained and frozen
      hydrated preparations, we examined whole basal body complexes and subcomplexes
      obtained by dissociation in acid. Dissociation occurs in steps, allowing us to
      obtain images of substructures lacking the M ring, lacking the M and S rings, and
      lacking the M and S rings and the proximal portion of the rod. We obtained images
      of the L and P ring subcomplex. The existence of a subcomplex missing only the M
      ring suggests either that the S and M rings derive from two different proteins,
      or that the M ring is a labile domain of a single protein, which makes up both
      rings. At the 25 to 30 A resolution of our averaged images, the L, P and S rings
      appear cylindrically symmetric. Images of the M ring show variability that may be
      due to differences in angular orientation of the grid, but equally could be due
      to structural variations. Three-dimensional reconstructions of these structures
      from the averaged images reveal the internal structure and spatial organization
      of these components.

PMID- 1370544
TI  - Mechanism of post-segregational killing by the hok/sok system of plasmid R1. Sok
      antisense RNA regulates hok gene expression indirectly through the overlapping
      mok gene.
AB  - The hok/sok locus of plasmid R1, which mediates plasmid stabilization by killing
      of plasmid-free segregants, codes for two RNAs, Hok mRNA and Sok antisense RNA.
      Hok mRNA encodes the Hok killer protein of 52 amino acid residues. Expression of
      hok is regulated post-transcriptionally by Sok antisense RNA. Killing of plasmid
      free daughter-cells by the hok/sok system is accomplished through differential
      decay of the Hok and Sok-RNAs: Hok mRNA is very stable while Sok-RNA decays
      rapidly, thus leading to derepression of Hok mRNA translation in plasmid-free
      segregants, ensuring a rapid and selective killing of these cells. Sok antisense
      RNA is complementary to the leader region of the Hok mRNA. However, the region of
      complementarity does not overlap with the hok Shine-Dalgarno sequence. Thus, Sok
      RNA regulates hok translation indirectly by an as yet unknown mechanism. We show
      here that Sok antisense RNA regulates the translation of another reading frame
      located in the hok/sok locus. This new reading frame, which overlaps with almost
      the entire hok gene, was denoted mok (mediation of killing). Point-mutations that
      prevent mok translation through the hok translational initiation region abolish
      efficient expression of hok. Furthermore, these mutations abolish the Sok-RNA
      mediated control of hok gene expression. Hence, the antisense-RNA-mediated
      regulation of the hok gene seems to occur via translational coupling between the
      hok and mok reading-frames.

PMID- 1370545
TI  - Bar to normal UGA translation by the selenocysteine tRNA.
AB  - The selC gene product, tRNA(Sec), inserts selenocysteine at UGA (opal) codons in
      a specialized mRNA context. We have investigated the action of the tRNA at
      ordinary UGA codons, normally not translated, by changing the unusual structural
      features of tRNA(Sec). Sequences in the D arm, CCA arm and variable arm of the
      tRNA all contribute to the prohibition against translation of ordinary UGA
      codons. One multiple mutant is a moderately efficient serine-inserting UGA
      suppressor tRNA.

PMID- 1370546
TI  - Cassette mutagenesis of the reverse transcriptase of human immunodeficiency virus
      type 1.
AB  - We constructed a series of BspMI cassettes that simplify the introduction of
      specific point mutations in the polymerase domain of human immunodeficiency virus
      type 1 reverse transcriptase. A series of point mutants were constructed by using
      these cassette vectors. The RNA-dependent DNA polymerase and RNase H activities
      of 20 point mutations in the conserved portion of the polymerase domain were
      assayed. All the mutations analyzed are conservative substitutions of
      evolutionarily conserved amino acids. The mutations were divided into four
      classes. The first class has little effect on either polymerase or RNase H
      activity. The second class affects RNase H but not polymerase activity, while the
      third class has a normal RNase H activity with diminished polymerase activity.
      The fourth class affects both activities.

PMID- 1370548
TI  - Vaccination with a synthetic peptide modulates lymphocytic choriomeningitis virus
      mediated immunopathology.
AB  - Vaccination with a nucleopeptide (NP 118; amino acids 118 to 132) representing a
      cytotoxic T-cell epitope of lymphocytic choriomeningitis virus (LCMV) can
      modulate immunopathology. Immunization with NP 118 protected H-2d mice against
      intracerebral infection with the LCMV-ARMSTRONG isolate. However, when NP 118
      primed H-2d mice were challenged intracerebrally with an intermediate dose (5 x
      10(4) PFU) of the LCMV-DOCILE strain, all mice primed with NP 118 emulsified in
      incomplete Freund's adjuvant died, whereas unprimed mice survived.
      Correspondingly, peptide vaccination enhanced specifically the cytotoxic T-cell
      response, influencing the critical balance between T-cell response and virus
      spread.

PMID- 1370547
TI  - Transactivation of the cytomegalovirus ICP36 gene promoter requires the alpha
      gene product TRS1 in addition to IE1 and IE2.
AB  - Very little is known about the human cytomegalovirus functions that activate
      gamma (late) gene expression. We have investigated the regulation of the human
      cytomegalovirus gamma gene encoding the ICP36 major late DNA-binding protein
      family (UL44). Transactivation of the ICP36 gene promoter was found to be
      absolutely dependent on the trs1 gene product when expressed in cells in
      conjunction with ie1 and ie2 gene products. Transactivation occurred poorly or
      not at all when any one of these three transactivators was omitted. TRS1 is a
      member of the US22 family of proteins and is encoded by a region near the L-S
      junction of the viral genome within the c repeat and adjacent Us sequences. TRS1
      is highly homologous to IRS1, which is encoded from the other copy of the c
      repeat, and plasmid constructs carrying the irs1 gene were also able to mediate
      transactivation of the ICP36 promoter. RNA blot analysis of steady-rate RNA
      throughout infection showed that the trs1 transcript was expressed with the
      kinetics of an alpha gene but its accumulation was delayed relative to that of
      ie1 and ie2 transcripts. On the basis of these experiments, TRS1 and IRS1 are
      proposed to be important intermediaries in the cascade of cytomegalovirus gene
      expression.

PMID- 1370550
TI  - Mapping of B-cell epitopes on the polypeptide chain of the Epstein-Barr virus
      major envelope glycoprotein and candidate vaccine molecule gp340.
AB  - The Epstein-Barr virus (EBV) major envelope glycoprotein gp340 is the subject of
      current efforts to develop an EBV subunit vaccine. The importance of gp340
      specific humoral immunity has been highlighted by studies of natural infection in
      humans and gp340 immunization of experimental animals. The former studies have
      demonstrated the presence of gp340-specific serum antibodies which mediate EBV
      neutralization, complement fixation, and antibody-dependent cellular
      cytotoxicity. The latter studies have often shown a correlation between the
      induction of gp340-specific EBV-neutralizing antibodies and protection from virus
      challenge. We have used a series of bacterial beta-galactosidase-gp340 fusion
      proteins and overlapping synthetic peptides from the gp340 open reading frame to
      map the positions of B-cell epitopes within the gp340 primary amino acid
      sequence. The data reported here indicate the presence of B-cell epitopes within
      the carboxy-terminal third of the gp340 polypeptide chain. These epitopes could
      not be detected with a peptide enzyme-linked immunosorbent assay, thereby
      suggesting that they are discontinuous. Affinity purification of antibodies with
      a gp340 fusion protein from the carboxy terminus of the gp340 polypeptide chain
      has been used to show that these antibodies are not EBV neutralizing in vitro.
      The consequences of these findings for future EBV vaccine development are
      considered.

PMID- 1370549
TI  - RNase H activity associated with reverse transcriptase from feline
      immunodeficiency virus.
AB  - Reverse transcription of retroviral genomes requires the action of an RNase H for
      template switching and primer generation. In this report, we compare enzymatic
      properties of the RNase H associated with the reverse transcriptase (RT) from
      feline immunodeficiency virus (FIV) and that from human immunodeficiency virus
      (HIV). Both enzymes displayed substrate preference for poly[3H](rG) . poly(dC)
      hybird over poly[3H](rA) . poly(dT) and cation preference for Mg2+ over Mn2+.
      Activity of the FIV RNase H upon poly(rG) . poly(dC) produced hydrolysis products
      from 1 to 6 nucleotides in length, similar to that reported for HIV. Dextran
      sulfates were effective inhibitors of both the FIV and HIV RNase H and RT
      activities. Nearly identical inhibition constants (0.12 nM) were obtained for all
      enzyme activities with dextran sulfate 500,000, while different inhibition
      constants were observed with dextran sulfate 8,000. Our results suggest that FIV
      and HIV RTs contain a conserved region that is sensitive to the larger dextran
      sulfate and that dextran sulfate 8,000 may interact at a different site or by a
      different mechanism.

PMID- 1370551
TI  - Defects in Moloney murine leukemia virus replication caused by a reverse
      transcriptase mutation modeled on the structure of Escherichia coli RNase H.
AB  - We have studied a mutant Moloney murine leukemia virus with a deletion in reverse
      transcriptase (RT) which is predicted to make its RNase H domain resemble
      structurally that of human immunodeficiency virus RT. This deletion was based on
      improved RNase H homology alignments made possible by the recently solved three
      dimensional structure for Escherichia coli RNase H. This mutant Moloney murine
      leukemia virus RT was fully active in the oligo(dT)-poly(rA) DNA polymerase assay
      and retained nearly all of wild-type RT's RNase H activity in an in situ RNase H
      gel assay. However, proviruses reconstructed to include this deletion were
      noninfectious. Minus-strand strong-stop DNA was made by the deletion mutant, but
      the amount of minus-strand translocation was intermediate to the very low level
      measured with RNase H-null virions and the high level seen with wild-type RT. The
      average length of translocated minus-strand DNA was shorter for the deletion
      mutant than for wild type, suggesting that mutations in the RNase H domain of RT
      also affect DNA polymerase activity.

PMID- 1370552
TI  - p53 mutations are not selected for in simian virus 40 T-antigen-induced tumors
      from transgenic mice.
AB  - Many diverse tumors contain cells that select for mutations at the p53 gene
      locus. This appears to be the case because the p53 gene product can act as a
      negative regulator of cell division or a tumor suppressor. These mutations then
      eliminate this activity of the p53 gene product. The simian virus 40 (SV40) large
      T antigen binds to p53 and acts as an oncogene to promote cellular transformation
      and initiate tumors. If the binding of T antigen to the p53 protein inactivated
      its tumor suppressor activity, there would be no selection pressure for p53
      mutants to appear in tumors. To test this idea, transgenic mice that carried and
      expressed the SV40 large T-antigen gene were created. Expression of the T antigen
      was directed to the liver, using the albumin promoter, and the choroid plexus,
      using the SV40 enhancer-promoter. A large number of papillomas (indicated in
      parentheses) of the choroid plexus (14), hepatocellular carcinomas (5), liver
      adenomas (10), and tumors of clear-cell foci (5) were examined for mutant and
      wild-type p53 genes and gene products. In all cases, the tumor extracts contained
      readily detectable T-antigen-p53 protein complexes. A monoclonal antibody
      specifically recognizing the wild-type p53 protein (PAb246) reacted with p53 in
      every tumor extract. A monoclonal antibody specifically recognizing mutant forms
      of the p53 protein (PAb240) failed to detect p53 antigens in these extracts.
      Finally, p53 partial cDNAs were sequenced across the regions of common mutations
      in this gene, and in every case only the wild-type sequence was detected. These
      results strongly support the hypothesis that T antigen inactivates the wild-type
      p53 tumor-suppressing activity and there is no need to select for mutations at
      the p53 locus.

PMID- 1370554
TI  - Transcription of the Epstein-Barr virus gene EBNA-1 from different promoters in
      nasopharyngeal carcinoma and B-lymphoblastoid cells.
AB  - Transcriptional expression of the Epstein-Barr virus (EBV) genome has been shown
      to differ markedly between nasopharyngeal carcinoma (NPC) cells and latent B-cell
      lines, with a more limited pattern of gene expression seen in NPC. EBNA-1 is the
      only nuclear antigen so far detected in both NPC and Burkitt's lymphoma cells. We
      found previously that in a human NPC tumor passaged in nude mice, designated C15,
      the EBNA-1 mRNA contained a novel splice site in the BamHI Q region of EBV which
      had not previously been described for B-cell lines. This lies within a region of
      the EBV genome to which EBNA-1 binds. Here, we further characterize the 5' region
      of EBNA-1 transcripts and identify two splicing patterns in C15 cells; we show
      that they are derived from a common promoter region in the BamHI F region of the
      viral genome. We also demonstrate that this region can function to initiate
      transcription of the chloramphenicol acetyltransferase gene in epithelial cells
      and that the promoter region is only partially methylated at CpG sites in the
      tumor. In contrast, a B-lymphoblastoid cell line derived from C15 uses a
      conventional promoter in BamHI-C/W for expression of EBNA-1.

PMID- 1370553
TI  - ICP22 homolog of equine herpesvirus 1: expression from early and late promoters.
AB  - The complete nucleotide sequence of the short region, made up of a unique segment
      (Us; 6.5 kb) bracketed by a pair of inverted repeat sequences (IR; 12.8 kb each),
      of the equine herpesvirus 1 (EHV-1) genome has been determined recently in our
      laboratory. Analysis of the IR segment revealed a major open reading frame (ORF)
      designated IR4. The IR4 ORF exhibits significant homology to the immediate-early
      gene US1 (ICP22) of herpes simplex virus type 1 and to the ICP22 homologs of
      varicella-zoster virus (ORF63), pseudorabies virus (RSp40), and equine
      herpesvirus 4 (ORF4). The IR4 ORF is located entirely within each of the inverted
      repeat sequences (nucleotides [nt] 7918 to 9327) and has the potential to encode
      a polypeptide of 469 amino acids (49,890 Da). Within the IR4 ORF are two
      reiterated sequences: a 7-nt sequence tandemly repeated 17 times and a 25-nt
      sequence tandemly repeated 13 times. Nucleotide sequence analyses of IR4 also
      revealed several potential cis-regulatory sequences, two TATA sequences separated
      by 287 nt, an in-frame translation initiation codon following each TATA sequence,
      and a single polyadenylation site. To address the nature of the mRNA species
      encoded by IR4, we used Northern (RNA) blot and S1 nuclease analyses. RNA mapping
      data revealed that IR4 has two promoters that are regulated differentially during
      a lytic infection. A 1.4-kb mRNA appears initially at 2 h postinfection and is an
      early transcript since its synthesis is not affected by the presence of
      phosphonoacetic acid, an inhibitor of EHV-1 DNA replication. In contrast, a 1.7
      kb mRNA appears at later times postinfection and is designated as a gamma-1
      transcript, since its synthesis is significantly reduced by phosphonoacetic acid.
      These IR4-specific mRNAs are 3' coterminal, have unique 5' termini, and would
      code for in-frame, overlapping, carboxy-coterminal proteins of 293 and 469 amino
      acids, respectively. Interestingly, the site of homologous recombination to
      generate the genome of EHV-1 defective interfering particles that initiate
      persistent infection occurs between nt 3244 and 3251 of UL3 (ICP27 homolog) and
      nt 9027 and 9034 of IR4 (ICP22 homolog). Thus, this recombination event would
      generate a unique ORF that would encode a potential protein whose amino end was
      derived from the N-terminal 193 amino acids of the ICP22 homolog and whose
      carboxyl end was derived from the C-terminal 68 amino acids of the ICP27 homolog.

PMID- 1370555
TI  - Restriction of porcine parvovirus replication in nonpermissive cells.
AB  - Swine testicle (ST) cells and Madin-Darby canine kidney (MDCK) cells differ in
      their ability to support replication of porcine parvovirus (PPV). Viral
      replication events in ST cells, a permissive cell type, and MDCK cells, a
      nonpermissive cell type, were compared in an attempt to elucidate putative
      mechanisms of restrictive virus replication. Radiolabeled PPV bound to the cell
      surface of both cell types equally well and the binding was shown to be PPV
      specific, indicating that the restriction was not at the cell surface level. In
      contrast, profound differences in intracellular events in PPV replication were
      observed between these two cell types. Synthesis of viral DNA was limited in MDCK
      cells in that the percentage of cells with replicative-form DNA as determined by
      strand-specific probe in situ hybridization was approximately 100-fold lower in
      MDCK cells than in ST cells at the same multiplicity of infection. Northern (RNA)
      blot analysis, using oligonucleotide probes derived from both structural and
      nonstructural protein-coding regions of the PPV genome, revealed four PPV mRNA
      transcripts from infected ST cells. Comparatively, RNA species from the
      structural protein coding region were actively transcribed in MDCK cells, but
      synthesis of RNA species from the nonstructural protein coding region was
      negligible. Immunoprecipitation of viral polypeptides revealed the three
      characteristic structural polypeptides, VP1, VP2, and VP3, along with the
      nonstructural polypeptide, NS-1 from ST cells. In contrast, neither viral
      structural or nonstructural polypeptides nor progeny virions were produced from
      MDCK cells. The data suggest that mechanisms controlling permissiveness of cells
      to PPV infection are associated with the level of viral DNA replication, RNA
      transcription, and viral antigen expression but not absorption to the cell
      surface.

PMID- 1370556
TI  - Detailed mapping of the antigenicity of the surface unit glycoprotein of equine
      infectious anemia virus by using synthetic peptide strategies.
AB  - We describe here a detailed analysis of the antigenic determinants of the surface
      unit glycoprotein (gp90) of equine infectious anemia virus (EIAV), using a
      comprehensive panel of synthetic peptides in enzyme-linked immunosorbent assays
      with immune serum from naturally and experimentally infected horses and with a
      panel of gp90-specific neutralizing and nonneutralizing monoclonal antibodies.
      The results of these studies identify immunoreactive segments throughout the
      conserved and variable domains of gp90 but localize immunodominant (100%
      reactivity) determinants to the amino and carboxyl termini of the glycoprotein
      molecule. Analysis of peptide reactivities with longitudinal serum samples taken
      from experimentally infected ponies revealed that antibody responses to conserved
      B-cell determinants appeared earlier and at higher titers than do antibodies
      specific for determinants contained in the variable domain of gp90. These
      observations suggest an evolution of antibody responses in EIAV-infected ponies
      that may correspond to the establishment of immunological control of virus
      replication and disease routinely observed in EIAV infections. In addition, the
      mapping of monoclonal antibody epitopes to peptides of 9 to 12 amino acids
      demonstrated that all of the neutralizing epitopes are located in the variable
      domain of gp90. The arrangement of neutralizing epitopes and critical structural
      considerations suggest that EIAV gp90 contains a principal neutralizing domain
      similar to the V3 loop of human immunodeficiency virus type 1. These antigenic
      analyses provide an important foundation for further analyzing the protective
      immune response generated during persistent EIAV infections and also provide
      potential peptide substrates for diagnostic assays and for vaccine strategies.

PMID- 1370557
TI  - Three epitopic peptides of the simian immunodeficiency virus Nef protein
      recognized by macaque cytolytic T lymphocytes.
AB  - In 8 of 12 experimentally infected macaques, the Nef SIVmac 251 protein was
      recognized by cytolytic T lymphocytes (CTL) and appeared strongly immunogenic.
      Here, we report experiments which have been performed by using synthetic peptides
      to precisely determine the epitopes recognized by macaque CTL. Three epitopes of
      the Nef protein have been defined as CTL targets in three macaques. The epitopic
      peptides are located in the central region of the protein, and all of them show
      high homology with peptides of the human immunodeficiency virus type 1 Nef
      protein recognized by human CTL in association with several human leukocyte
      antigen molecules. These results suggest that (i) the Nef protein is a good
      candidate for vaccination not only because of its early expression but also
      because of its high immunogenicity for CTL, (ii) long peptides covering the
      central region of this protein could be used as vaccines and could cross the
      major histocompatibility complex barrier in a large variety of individuals, and
      (iii) the rhesus macaque is a good animal model in which to test for protection
      by CTL.

PMID- 1370558
TI  - Identification and characterization of a neutralization site within the second
      variable region of human immunodeficiency virus type 1 gp120.
AB  - Two monoclonal antibodies designated BAT085 and G3-136 were raised by immunizing
      BALB/c mice with gp120 purified from human immunodeficiency virus type 1 (HIV-1)
      IIIB-infected H9 cell extracts. Among three HIV-1 laboratory isolates (IIIB, MN,
      and RF), BAT085 neutralized only IIIB infection of CEM-SS cells, whereas G3-136
      neutralized both IIIB and RF. These antibodies also neutralized a few primary HIV
      1 isolates in the infection of activated human peripheral blood mononuclear
      cells. In indirect immunofluorescence assays, BAT085 bound to H9 cells infected
      with IIIB or MN, while G3-136 bound to H9 cells infected with IIIB or RF, but not
      MN. Using sequence-overlapping synthetic peptides of HIV-1 IIIB gp120, the
      binding site of BAT085 and G3-136 was mapped to a peptidic segment in the V2
      region (amino acid residues 169 to 183). The binding of these antibodies to
      immobilized gp120 was not inhibited by the antibodies directed to the principal
      neutralization determinant in the V3 region or to the CD4-binding domain of
      gp120. In a competition enzyme-linked immunosorbent assay, soluble CD4 inhibited
      G3-136 but not BAT085 from binding to gp120. Deglycosylation of gp120 by endo
      beta-N-acetylglucosaminidase H or reduction of gp120 by dithiothreitol diminished
      its reactivity with G3-136 but not with BAT085. These results indicate that the
      V2 region of gp120 contains multiple neutralization determinants recognized by
      antibodies in both a conformation-dependent and -independent manner.

PMID- 1370559
TI  - Mutations within the proteolytic cleavage site of the Rous sarcoma virus
      glycoprotein define a requirement for dibasic residues for intracellular
      cleavage.
AB  - We investigated the amino acid sequence requirements for intracellular cleavage
      of the Rous sarcoma virus glycoprotein precursor by introducing mutations into
      the region encoding the cleavage recognition site (Arg-Arg-Lys-Arg). In addition
      to mutants G1 (Arg-Arg-Glu-Arg) and Dr1 (deletion of all four codons) that we
      have reported on previously (L. G. Perez and E. Hunter, J. Virol. 61:1609-1614,
      1987), we constructed two additional mutants, AR1 (Arg-Arg-Arg-Arg), in which the
      highly conserved lysine is replaced by an arginine, and S19 (Ser-Arg-Glu-Arg), in
      which no dibasic pairs remain. The results of these studies demonstrate that when
      the cleavage sequence is deleted (Dr1) or modified to contain unpaired basic
      residues (S19), intracellular cleavage of the glycoprotein precursor is
      completely blocked. This demonstrates that the cellular endopeptidase responsible
      for cleavage has a stringent requirement for the presence of a pair of basic
      residues (Arg-Arg or Lys-Arg). Furthermore, it implies that the cleavage enzyme
      is not trypsinlike, since it is unable to recognize arginine residues that are
      sensitive to trypsin action. Substitution of the mutated genes into a replication
      competent avian retrovirus genome showed that cleavage of the glycoprotein
      precursor was not required for incorporation into virions but was necessary for
      infectivity. Treatment of BH-RCAN-S19-transfected turkey cells with low levels of
      trypsin resulted in the release of infectious virus, demonstrating that exogenous
      cleavage could generate a biologically active glycoprotein molecule.

PMID- 1370561
TI  - Phenotypic characterization of infiltrating leukocytes in benign prostatic
      hyperplasia.
AB  - This study for the first time elaborates on cells of the immune system present in
      benign prostatic hyperplasia (BPH). Compared with normal prostate, all BPH
      derived specimens revealed a marked increase of CD45+ leukocytes,
      characterization of which demonstrated three major cell types, i.e., CD3+ T
      lymphocytes, CD11c+ macrophages and CD20+ B lymphocytes. Frequencies of CD3+
      cells/mm2 of cryocut sections were increased at least 10 times in BPH specimens,
      and the CD8+:CD4+ T suppressor/cytotoxic:T helper cell ratio was reversed. The
      infiltrating leukocytes predominantly populate the interstitium and accumulate
      around epithelial ducts which, however, were found to be invaded and/or destroyed
      only in a number of cases. Phenotypic alterations of surface antigen expression
      on prostate epithelial cells in BPH that might be due to the presence of
      lymphocytes were examined by using monoclonal antibodies (mAb) directed against
      human leukocyte antigens (HLA). Whereas anti-HLA-DR reactivity in normal prostate
      is restricted to small numbers of macrophages and includes neither prostate
      epithelial cells nor prostate T cells, it was found to be dramatically increased
      in BPH, comprising CD45+ cells and prostate epithelial cells as demonstrated by
      double-staining with anti-cytokeratin or anti-prostate-specific antigen. A mean
      of 40% of analyzed epithelial glands in BPH reacted with anti-HLA-DR, but not
      with anti-DQ or -DP monoclonal antibodies. A new method for the enrichment of
      prostate-derived lymphocytes was established to facilitate phenotypic analysis by
      flow cytometry, demonstrating 70 to 80% of enriched CD45+ cells to stain for CD3,
      approximately 60% thereof for CD4, 30% for CD8, and the remaining 10% with anti
      CD20, a pan-B-cell marker. Flow cytometry showed that, in contrast to peripheral
      T cells, both CD4+ and CD8+ prostatic T cells were positive for the T cell
      activation markers HLA-DR and interleukin-2-receptor.

PMID- 1370562
TI  - Transposons: friends or foes?

PMID- 1370560
TI  - The third subunit of protein phosphatase 2A (PP2A), a 55-kilodalton protein which
      is apparently substituted for by T antigens in complexes with the 36- and 63
      kilodalton PP2A subunits, bears little resemblance to T antigens.
AB  - The small and middle T (tumor) antigens of polyomavirus have been shown
      previously to associate with the 36-kDa catalytic subunit and the 63-kDa
      regulatory subunit of protein phosphatase type 2A, apparently substituting for a
      normal third 55-kDa regulatory subunit (D.C. Pallas, L.K. Shahrik, B.L. Martin,
      S. Jaspers, T.B. Miller, D.L. Brautigan, and T.M. Roberts, Cell 60:167-176,
      1990). To facilitate a comparison of the normal regulatory subunit and T
      antigens, we isolated a 2.14-kb cDNA clone encoding this 55-kDa subunit from a
      rat liver library. Using a probe from the coding region of this gene, we detected
      a major 2.4-kb mRNA transcript in liver and muscle RNAs. The 55-kDa protein
      phosphatase 2A subunit purified from rat skeletal muscle generates multiple
      species when analyzed on two-dimensional gels. Transcription and translation of
      the clone in vitro produced a full-length protein that comigrated precisely on
      two-dimensional gels with three of these species, indicating that the 55-kDa
      protein is apparently modified similarly in vivo and in reticulocyte lysates.
      Additional species in the purified preparation were not found in the translate,
      suggesting that there are probably two or more isoforms of this protein in rat
      muscle. Somewhat surprisingly, there was no clear homology with T-antigen amino
      acid sequences.

PMID- 1370563
TI  - FK 506, cardiac transplantation, and graft-vessel disease.

PMID- 1370564
TI  - Pseudomonas cepacia infection in cystic fibrosis.

PMID- 1370565
TI  - Metastatic head and neck malignancy treated using MRI guided interstitial laser
      phototherapy: an initial case report.
AB  - Interstitial laser phototherapy (ILP) guided by magnetic resonance imaging (MRI)
      may become an attractive adjunctive modality for the treatment of deep and
      surgically inaccessible tumors of the head and neck when accurate methods of
      laser dosimetry and "real-time" monitoring techniques with the MRI are
      introduced. We recently demonstrated in ex vivo and in vivo models, a linear
      relationship between levels of laser energies, thermal profiles, MR signal
      intensity changes, and histopathological tissue damage. Results of treatment in a
      patient with an unresectable large right jugulodigastric metastatic squamous
      carcinoma using new approach of MRI guided ILP are now reported. The patient
      complained of significant right-sided neck pain and headaches secondary to a
      rapidly growing metastatic lymphadenopathy which recurred after previous surgery,
      radiation, and chemotherapy. Two treatment sessions were used at an interval of 2
      weeks. Each treatment was performed in the MRI suite under heavy sedation. Using
      a 600-microns bare fiber of the Nd:YAG laser implanted interstitially under MR
      guidance, the metastatic node was treated at three sites. T1- and T2-weighted
      images were performed prior to, immediately after, 24 and 48 hours, and 4, 5, 7,
      9, 16, and 25 days post-treatment. Successful relief of pain and growth arrest of
      this node was observed after the second treatment and at the 3-month follow-up.
      These results demonstrate that this technique of ILP guided by MRI may be
      feasible in humans, and will become clinically practical when appropriate methods
      of dosimetry and instrumentation are developed.

PMID- 1370567
TI  - The incidence and distribution of cupular deposits in the labyrinth.
AB  - Findings of large basophilic staining deposits on the cupula of the posterior
      semicircular canal ampulla have been used in part to explain the clinical
      phenomenon of benign positional vertigo (BPV). Although it is generally agreed
      that cupulolithiasis may involve other canal ampullae, the precise nature,
      distribution, and origin of these deposits remains unclear. In order to provide a
      better understanding of this finding, a series of 566 temporal bone specimens
      from the Ear Pathology Research Laboratory at the University of Toronto were
      reviewed. The results from this survey and speculations concerning the nature and
      formation of these deposits are discussed.

PMID- 1370566
TI  - Nucleolar organizer regions in squamous cell carcinoma of the head and neck.
AB  - Nucleolar organizer regions are collections of nucleolar proteins associated with
      ribosomal genes that can be visualized in histologic sections using a silver
      colloid stain, thus the term silver-staining nucleolar organizer region (AgNOR).
      In some tissues, the number of AgNORs per nucleus correlates with cellular
      proliferation and, independently, with malignant change. AgNORs were studied in
      66 paraffin-embedded head and neck squamous cell carcinomas and in 12 samples of
      normal tonsillar squamous epithelium. Carcinomas had a significantly higher mean
      AgNOR count than the benign epithelium (P less than .0001). Among carcinomas,
      mean AgNOR count increased with stage of the disease (P less than .001), but
      there was no significant correlation with histologic grade or DNA ploidy as
      determined by flow cytometry. These data suggest that AgNOR count should be
      evaluated as a possible aid in differentiating benign from malignant squamous
      epithelial proliferations in the head and neck, and also possibly as a prognostic
      marker in these carcinomas.

PMID- 1370568
TI  - Vasoactive therapy versus placebo in the treatment of sudden hearing loss: a
      double-blind clinical study.
AB  - Twenty-seven patients suffering from sudden sensorineural hearing loss (SHL) were
      randomly assigned to one of two groups: a treatment group (n = 13) receiving
      intravenous procaine and low-molecular-weight dextran, and a placebo control
      group (n = 14). The effect of treatment was analyzed by means of an analysis of
      variance and covariance procedures. Results indicated nonsignificant differences
      between the groups on all outcome indices measured. Sex, age, time since the
      onset of symptoms to the initiation of therapy, audiogram configuration, and
      initial severity of hearing loss did not significantly affect the results. These
      findings suggest that the therapeutic effects of this vasodilator are not
      superior to a placebo.

PMID- 1370569
TI  - Binding characteristics of naftopidil and alpha 1-adrenoceptor antagonists to
      prostatic alpha-adrenoceptors in benign prostatic hypertrophy.
AB  - Binding properties of naftopidil and alpha 1-adrenoceptor antagonists to alpha
      adrenoceptors in prostates from benign prostatic hypertrophy (BPH) were
      characterized by radioreceptor assays using [3H]prazosin and [3H]rauwolscine.
      Specific binding of [3H]prazosin and [3H]rauwolscine in human prostatic membranes
      was saturable and of high affinity, and it showed a pharmacological specificity
      which characterized alpha 1 and alpha 2-adrenoceptors, respectively. Naftopidil
      and several alpha 1 antagonists competed for prostatic [3H]prazosin binding in
      order: R-(-)-YM-12617 greater than prazosin greater than bunazosin greater than
      terazosin greater than naftopidil greater than urapidil, and the inhibitory
      effect (Ki = 11.6 nM) of naftopidil was 10 to 45 times less potent than
      quinazoline derivatives such as prazosin, bunazosin and terazosin. The potencies
      of these antagonists in competing for [3H]prazosin binding sites in human
      prostates correlated well with their pharmacological potencies (pA2). Scatchard
      analysis indicated that the decrease of prostatic [3H]prazosin binding by
      naftopidil was due to a marked increase in the Kd value without a change in the
      Bmax value. The inhibition of prostatic [3H]prazosin binding by naftopidil was
      reversible. Naftopidil also inhibited prostatic [3H]rauwolscine binding (Ki =
      70.0 nM). Thus, it is suggested that naftopidil antagonizes alpha 1-adrenoceptors
      in human prostates in a competitive and reversible manner.

PMID- 1370570
TI  - Novel monoclonal antibodies to cyclosporine A: characterization and epitope
      mapping with cyclosporine analogs and cyclophilin.
AB  - Monoclonal antibodies to cyclosporine A (Cs), a potent immunosuppressant, were
      generated in BALB/c mice using a novel antigen prepared by linking Cs to a
      protein carrier via a photoactive cross-linking reagent, 4-benzoylbenzoic acid
      (BBa). Twenty-two monoclonal anti-Cs antibodies were generated, using Cs-BBa
      bovine serum albumin (Cs-BBa-BSA) as the immunogen. They were characterized with
      respect to affinity by Scatchard analysis of a radioimmunoassay (RIA), and with
      respect to specificity by an ELISA in which a series of singly substituted Cs
      derivatives were examined as inhibitors. McAb affinities ranged from 5 x 10(-8) M
      to 2 x 10(-10) M. Based on ELISA inhibition data with Cs analogs, and on the
      binding to two Cs-BSA conjugates in which opposite sides of the Cs molecule are
      exposed, the antibodies fell into five epitope recognition groups. Binding to Cs
      was also studied by ELISA in competition with cyclophilin (CyP), a Cs-binding
      protein whose epitope specificity has been well characterized. Competition by CyP
      was found to correlate with antibody specificity, not with affinity, i.e. CyP
      competed best with antibodies having specificities most similar to that of CyP.
      Epitope mapping can, therefore, be accomplished in a system in which two
      different species of binding proteins compete for the same antigen. This type of
      characterization may be useful in identifying antibodies whose combining sites
      mimic those of a receptor.

PMID- 1370571
TI  - Immunochemical characterization of antigenic domains on human IL-2: spatially
      distinct epitopes are associated with binding to the p55 and p70 subunits of IL-2
      receptor.
AB  - We have isolated and characterized 8 mAb against human rIL-2. All recognize
      nonglycosylated rIL-2 in liquid phase with similar affinities (Kd approximately 1
      nM). Based on the epitopes of the IL-2 molecule that they recognize and their
      pattern of reactivity against glycosylated and non-glycosylated IL-2, they have
      been classified into four groups. The first group of anti-IL-2 mAb (2C4, 19B11
      and 12C2) inhibits IL-2 binding to p70 IL-2R, while the second one (16F11, 18E1
      and 2A4) prevents its binding to p55 IL-2R. These two groups neutralize IL-2
      activity in a T cell proliferation assay equally well, due to their similar
      inhibition of IL-2 binding to high affinity IL-2R. Two mAb, 3H9 and 17F4,
      recognize separate epitopes on IL-2 molecule, are poor inhibitors of IL-2
      binding, and they are inefficient in the neutralization of its biological
      activity; they have been assigned to the third and fourth groups, respectively.
      These results show that mAb from the first and second group recognize two
      epitopes of the human IL-2 molecule which probably overlap the p70 IL-2R and p55
      IL-2R binding sites, respectively. In addition, these areas together form the
      high affinity IL-2R binding site. The two mAb from the third and fourth group
      recognized epitopes of IL-2 not directly involved in IL-2 binding to its
      receptor. All eight mAb anti-human IL-2 recognize murine IL-2 and with the
      exception of one, 17F4 mAb are also able to neutralize it in a T cell
      proliferation assay. The relationship between the structure and the function of
      the IL-2 molecule is discussed.

PMID- 1370572
TI  - A calcium-binding monoclonal antibody that recognizes a non-calcium-binding
      epitope in the short consensus repeat units (SCRs) of complement C1r.
AB  - C1r is a Ca(2+)-binding serine protease that interacts with two other plasma
      proteins, C1q and C1s, to form C1, the first component of the complement cascade.
      A monoclonal antibody, BG6, has been produced which binds to C1r only in the
      presence of Ca2+, requiring 3-5 microM Ca2+ for half-maximal binding. The
      antibody reacts with native and heat-denatured C1r, and with zymogen C1r, but
      does not cross-react with C1s or C1q. BG6 did not significantly affect the
      esterolytic activity of C1r toward a synthetic thioester substrate nor the
      hemolytic activity of C1 reconstituted from subcomponents in the presence of the
      antibody. A tryptic fragment of C1r which consists of the C-terminal gamma region
      of the A chain disulfide-linked to the B chain (gamma B) binds in a Ca(2+)
      dependent manner to BG6-Sepharose. Western blotting experiments have further
      localized the epitope to the gamma region of the A chain, which is composed of
      two short consensus repeat (SCR) units. The N-terminal alpha region contains the
      only previously determined Ca(2+)-binding site in the C1r molecule. Equilibrium
      dialysis experiments confirmed that C1r-gamma B does not bind Ca2+, and showed
      that antibody BG6 and the gamma B/BG6 complex do bind Ca2+. Thus, the Ca(2+)
      dependent nature of this interaction is due exclusively to binding of the metal
      ion to the antibody. Equilibrium dialysis and immunoblotting have further
      localized the Ca(2+)-binding site to the Fab fragment of BG6, indicating that the
      metal-induced conformational change residues in or near the variable region of
      the IgG. BG6 may set a precedent for the preparation of Ca(2+)-dependent
      antibodies to non-Ca(2+)-binding epitopes in other proteins.

PMID- 1370573
TI  - Mapping of monoclonal antibody binding sites on CNBr fragments of the S-layer
      protein antigens of Rickettsia typhi and Rickettsia prowazekii.
AB  - The 120 kDa surface protein antigens (SPAs) of typhus rickettsiae lie external to
      the outer membrane in regular arrays and chemically resemble the S-layer proteins
      of other bacteria. These proteins elicit protective immune responses against the
      rickettsiae. In order to study the immunochemistry of these proteins, purified
      SPAs from Rickettsia typhi and Rickettsia prowazekii were fragmented with CNBr.
      The fragments were separated by SDS-PAGE and were recovered on PVDF membrane
      following electroblotting. The origin of eight major fragments from R. prowazekii
      and seven major fragments from R. typhi was determined by automated N-terminal
      amino acid sequencing and by comparison with the DNA sequence encoding R.
      prowazekii SPA. The cleavage patterns and protein sequences of the two proteins
      differed significantly. CNBr fragments corresponding to the C-terminus (amino
      acid 1372-1612 of the deduced sequence from encoding gene spaP) were not present
      in both SPAs. This suggests that the corresponding C-terminal region was not
      synthesized or was removed during SPA translocation to the cell surface. Modified
      amino acids were detected in each protein. Eighteen monoclonal antibodies
      selected for varied reactivity with both native and denatured SPA proteins could
      be classified into eight different types based on western blot analysis of the
      CNBr fragments. Six of the monoclonal antibody types reacted predominantly with a
      single region of the SPAs. Two types of antibodies bound to several CNBr
      fragments which contained both limited sequence similarity and modified amino
      acids either of which might account for the multisite binding of these
      antibodies.

PMID- 1370574
TI  - Peripheral nerve injury triggers central sprouting of myelinated afferents.
AB  - The central terminals of primary afferent neurons are topographically highly
      ordered in the spinal cord. Peripheral receptor sensitivity is reflected by
      dorsal horn laminar location: low-threshold mechanoreceptors terminate in laminae
      III and IV (refs 2, 3) and high-threshold nociceptors in laminae I, II and V
      (refs 4,5). Unmyelinated C fibres, most of which are nociceptors, terminate
      predominantly in lamina II (refs 5, 7). There is therefore an anatomical
      framework for the transfer of specific inputs to localized subsets of dorsal horn
      neurons. This specificity must contribute to the relationship between a low
      intensity stimulus and an innocuous sensation and a noxious stimulus and pain. We
      now show that after peripheral nerve injury the central terminals of axotomized
      myelinated afferents, including the large A beta fibres, sprout into lamina II.
      This structural reorganization in the adult central nervous system may contribute
      to the development of the pain mediated by A-fibres that can follow nerve lesions
      in humans.

PMID- 1370575
TI  - Engagement of the high-affinity IgE receptor activates src protein-related
      tyrosine kinases.
AB  - The high-affinity IgE receptor (Fc epsilon RI), which is expressed on the surface
      of mast cells and basophils, has a central role in immediate allergic responses.
      In the rat basophilic leukaemia cell line RBL-2H3, which is a model system for
      the analysis of Fc epsilon RI-mediated signal transduction, surface engagement of
      Fc epsilon RI induces histamine release and the tyrosine phosphorylation of
      several distinct proteins. Although the alpha, beta, and gamma subunits of Fc
      epsilon RI lack intrinsic tyrosine protein kinase (TPK) activity, a kinase that
      copurifies with Fc epsilon RI phosphorylates the beta and gamma subunits of the
      receptor on tyrosine residues. We report here that in RBL-2H3 cells, p56lyn and
      pp60c-src are activated after Fc epsilon RI crosslinking, and p56lyn
      coimmunoprecipitates with Fc epsilon RI. In the mouse mast-cell line PT-18,
      another cell type used to study FC epsilon RI-mediated signalling, tyrosine
      phosphorylation of proteins is also an immediate consequence of receptor
      crosslinking. Notably, the only detectable src protein-related TPK in PT-18 cells
      is p62c-yes, and it is this TPK that is activated on Fc epsilon RI engagement and
      coimmunoprecipitates with the receptor. Therefore, it seems that different src
      protein-related TPKs can associate with the same receptor and become activated
      after receptor engagement.

PMID- 1370576
TI  - Developmental switch of CREM function during spermatogenesis: from antagonist to
      activator.
AB  - Mammalian spermatogenesis consists of a series of complex developmental processes
      controlled by the pituitary-hypothalamic axis. This flow of biochemical
      information is directly regulated by the adenylate cyclase signal transduction
      pathway. We have previously described the CREM (cyclic AMP-responsive element
      modulator) gene which generates, by cell-specific splicing, alternative
      antagonists of the cAMP transcriptional response. Here we report the expression
      of a novel CREM isoform (CREM tau) in adult testis. CREM tau differs from the
      previously characterized CREM antagonists by the coordinate insertion of two
      glutamine-rich domains that confer transcriptional activation function. During
      spermatogenesis there was an abrupt switch in CREM expression. In premeiotic germ
      cells CREM is expressed at low amounts in the antagonist form. Subsequently, from
      the pachytene spermatocyte stage onwards, a splicing event generates exclusively
      the CREM tau activator, which accumulates in extremely high amounts. This
      splicing-dependent reversal in CREM function represents an important example of
      developmental modulation in gene expression.

PMID- 1370577
TI  - Cell physiology. Controls on calcium influx.

PMID- 1370578
TI  - The pediatric nurse practitioner in a surgical inpatient setting.

PMID- 1370579
TI  - Nonrandom structures in the locomotor behavior of Halobacterium: a bifurcation
      route to chaos?
AB  - Halobacteria spontaneously reverse their swimming direction about every 10-15 s.
      They respond to light stimuli by a transient perturbation of this rhythm. During
      periodic stimulation the system shows features that are known from nonlinear
      oscillators. Increasing stimulation frequencies cause the following phenomena:
      (i) the frequency of reversals follows the stimulation frequency, (ii) transition
      to a state where a long and a short interval occur alternatingly and further
      transition to four interval lengths, (iii) appearance of irregular interval
      sequences, which, in a two-dimensional plot of successive intervals, reveal
      clearly discernible structures and suggest chaotic motion. A similar series of
      events can be induced in the absence of periodic stimulation, when a control
      parameter is changed to various constant levels. The data suggest that the system
      is governed by deterministic dynamical laws.

PMID- 1370580
TI  - Identification of human neutralization-inducing regions of the human
      immunodeficiency virus type 1 envelope glycoproteins.
AB  - Four major neutralizing regions of the human immunodeficiency virus type 1 (HIV
      1) envelope glycoprotein were identified and characterized with a panel of 80 HIV
      1 antibody-positive human sera. Levels of neutralizing antibodies against the HIV
      1 strains IIIB, SF2, and RF were compared with reactivity in ELISAs against
      peptides that correspond to certain regions of the HIV-1 envelope. A correlation
      between high neutralizing activity and strong seroreactivity against specific
      peptides suggested that the corresponding regions might be involved in
      neutralization. This was further substantiated by using peptides to inhibit
      neutralization by a panel of 10 HIV-1 antibody-positive sera. The positions of
      three neutralizing sites, defined earlier mostly by antisera from animals, were
      confirmed in the present study. Human sera thus recognize the strain-specific
      third variable region of gp120 (amino acids 304-318), the C-terminal end of gp120
      (amino acids 489-508), and the conserved region in the intracellular part of gp41
      (amino acids 732-746). It is likely that these different regions mediate help
      rather than self-sufficient neutralization. Furthermore, a human neutralizing
      region was detected in a conserved part of gp41 (amino acids 647-671).
      Accordingly, neutralizing antibodies directed to this region were found to be
      cross-reactive between HIV-1 strains. Peptides corresponding to these four
      regions were able to inhibit neutralization mediated by serum from HIV-1 antibody
      positive individuals. These results indicate that this conserved B-cell epitope
      of the HIV-1 envelope elicits a virus-neutralizing antibody response during
      natural infection in humans and may therefore be considered for inclusion in a
      vaccine against HIV-1.

PMID- 1370581
TI  - Termination of second messenger signaling in olfaction.
AB  - By using isolated rat olfactory cilia and a fast kinetics methodology, it has
      been demonstrated that odorant-induced second messenger signaling in the
      millisecond time range is terminated via phosphorylation reactions catalyzed by
      specific protein kinases. The cyclic adenosine nucleotide pathway is turned off
      by kinase A activity, whereas the inositol trisphosphate cascade is terminated by
      kinase C. The data support the concept that desensitization of odorant responses
      involves phosphorylation of key elements in the transduction cascade.

PMID- 1370582
TI  - Crystal structure of an Okazaki fragment at 2-A resolution.
AB  - In DNA replication, Okazaki fragments are formed as double-stranded intermediates
      during synthesis of the lagging strand. They are composed of the growing DNA
      strand primed by RNA and the template strand. The DNA oligonucleotide
      d(GGGTATACGC) and the chimeric RNA-DNA oligonucleotide r(GCG)d(TATACCC) were
      combined to form a synthetic Okazaki fragment and its three-dimensional structure
      was determined by x-ray crystallography. The fragment adopts an overall A-type
      conformation with 11 residues per turn. Although the base-pair geometry,
      particularly in the central TATA part, is distorted, there is no evidence for a
      transition from the A- to the B-type conformation at the junction between RNA.DNA
      hybrid and DNA duplex. The RNA trimer may, therefore, lock the complete fragment
      in an A-type conformation.

PMID- 1370583
TI  - Inflammatory leukocytes and cytokines in the peptide-induced disease of
      experimental allergic encephalomyelitis in SJL and B10.PL mice.
AB  - Experimental allergic encephalomyelitis (EAE) was generated in SJL and B10.PL
      mice by using the synthetic myelin basic protein peptides. Inflammation in brain
      and spinal cord preceded clinical signs of disease. Infiltrating lymphocytes were
      predominantly Lyt1+ (CD5+), L3T4+ (CD4+) T cells, until day 18. After that,
      F4/80+ monocyte/macrophages outnumbered T cells. Ia+ cells were microglia,
      macrophages, and endothelial cells, but Ia was not detectable on astrocytes in
      this EAE model. Ia+ endothelial cells appeared later in the disease than Ia+
      microglia and macrophages, suggesting that antigen presentation at the blood
      brain barrier is not initially responsible for inflammation. Cells staining for
      interferon gamma, interleukin 2 (IL-2), and IL-2 receptors were more prominent
      than IL-4, IL-5, lymphotoxin (LT), and tumor necrosis factor alpha (TNF-alpha),
      which occurred transiently in the second week and were associated with fewer
      cells. TNF-alpha and LT were never seen in spinal cord, suggesting that these
      cytokines are not responsible for initiation of clinical disease. Few or no cells
      stained for IL-6, IL-1, or transforming growth factor beta. Control animals
      injected with complete Freund's adjuvant in saline or control antigen
      demonstrated no inflammatory cell infiltration or cytokine production. Thus, our
      findings suggest a peptide-induced EAE model in which Th1 T-cell-macrophage
      interactions result in the disease process.

PMID- 1370584
TI  - Interkinase domain of kit contains the binding site for phosphatidylinositol 3'
      kinase.
AB  - Our previous analysis of the signal transduction pathway used by the c-kit
      encoded receptor for the stem cell factor (SCF) indicated efficient coupling to
      the type I phosphatidylinositol 3' kinase (PI3K). In an attempt to localize the
      receptor's site of interaction with PI3K, we separately deleted either the
      noncatalytic 68-amino-acid-long interkinase domain or the carboxyl-terminal
      portion distal to the catalytic sequences. Loss of ligand-induced association of
      PI3K with the former deletion mutant and retention of the PI3K association by the
      carboxyl-terminally deleted receptor implied interactions of PI3K with the kinase
      insert. This was further supported by partial inhibition of the association by an
      anti-peptide antibody directed against the kinase insert and lack of effect of an
      antibody directed to the carboxyl tail of the SCF receptor. A bacterially
      expressed kinase insert domain was used as a fusion protein to directly test its
      presumed function as a PI3K association site. This protein bound PI3K from cell
      lysate as demonstrated by PI3K activity and by an associated phosphoprotein of 85
      kDa. The association was dependent on phosphorylation of the tyrosine residues on
      the expressed kinase insert. On the basis of these observations, we conclude that
      the kinase insert domain of the SCF receptor selectively interacts with the p85
      regulatory subunit of PI3K and that this association requires phosphorylation of
      tyrosine residues in the kinase insert region, with apparently no involvement of
      the bulk cytoplasmic structure or tyrosine kinase function of the receptor.

PMID- 1370585
TI  - Pituitary follicular cells secrete an inhibitor of aortic endothelial cell
      growth: identification as leukemia inhibitory factor.
AB  - Medium conditioned by bovine pituitary follicular cells paradoxically inhibits
      the growth of adult bovine aortic endothelial (ABAE) cells at dilutions that are
      instead mitogenic to adrenal cortex capillary endothelial (ACCE) cells,
      suggesting that follicular cells secrete a growth inhibitor with a selectivity
      for ABAE cells. The ABAE cell inhibitory activity was purified to apparent
      homogeneity by a combination of size-exclusion chromatography, ion-exchange
      chromatography, and two reversed-phase steps on a C4 column. Microsequencing of
      the purified material revealed a single NH2-terminal amino acid sequence,
      identical to that of leukemia inhibitory factor (LIF), a glycoprotein originally
      identified by its ability to inhibit the growth of MT1 mouse leukemia cells and
      subsequently found to have numerous effects. Recombinant human LIF inhibited the
      growth of ABAE cells as effectively as transforming growth factor beta (TGF beta
      1). However, it failed to inhibit markedly the growth of ACCE cells, whereas TGF
      beta 1 dramatically inhibited their growth. Recombinant human LIF also failed to
      induce a significant angiogenic response in the chicken chorioallantoic membrane,
      indicating that, unlike TGF beta, LIF probably does not induce the release of
      direct-acting angiogenic factors from inflammatory cells. The presence of LIF in
      follicular cells may relate to the peculiar vascular organization of the
      pituitary gland, where no arteries reach the pars distalis and all of the blood
      supply to this area is by capillaries.

PMID- 1370587
TI  - [The treatment of terminal dyspnea].
AB  - Dyspnea can be defined as an unusual perception of respiration and/or urge to
      breath more than usual. Up to 70% of all tumour patients suffer at one time from
      this complaint, and often only an incomplete palliation is achieved. Dyspnea in
      the tumour patient is often associated with anxiety, which leads itself to a
      further exacerbation of dyspnea (through increased respiratory work and dead
      space ventilation). A thorough evaluation should exclude treatable causes of
      dyspnea such as atelectasis, pleural effusions, pneumonias, congestive heart
      failure, pulmonary emboli, reversible exacerbations of coexisting obstructive
      lung disease, central tumour obstruction and pericardial effusion. Therapeutic
      measures include bronchoscopic suction of retained secretions and physical
      measures to reduce secretions. Supplemental oxygen is indicated in hypoxemic
      patients and in those who derive benefit of it. The nonspecific drug therapy with
      benzodiazepines and/or opiates remains clinically useful, although its efficacy
      is questioned by some controlled studies.

PMID- 1370586
TI  - Mechanisms of the inhibition of reverse transcription by antisense
      oligonucleotides.
AB  - We have demonstrated that the synthesis of cDNA by avian myeloblastosis virus and
      Moloney murine leukemia virus reverse transcriptases can be prevented by
      oligonucleotides bound to the RNA template approximately 100 nucleotides remote
      from the 3' end of the primer. The RNA was truncated at the level of the
      antisense oligonucleotide-RNA duplex during the reverse transcription. The key
      role played by the reverse transcriptase-associated RNase H activity in the
      inhibition process was shown by the use of (i) inhibitors of RNase H (NaF or
      dAMP), (ii) Moloney murine leukemia virus reverse transcriptase devoid of RNase H
      activity, or (iii) alpha-analogues of oligomers that do not elicit RNase H
      catalyzed RNA degradation. In all three cases the inhibitory effect was either
      reduced (NaF, dAMP) or totally abolished. However, an alpha-oligomer bound to the
      sequence immediately adjacent to the primer-binding site prevented reverse
      transcription. Therefore, initiation of polymerization can be blocked by means of
      an RNase H-independent mechanism, whereas arrest of a growing cDNA strand can be
      achieved only by an oligonucleotide mediating cleavage of the template RNA.

PMID- 1370588
TI  - [Palliative measures in tumor-induced obstruction of the airways].
AB  - Local stenoses of the central airways in malignant inoperable disease are
      sometimes present at the time of diagnosis or develop over time after the
      completion of systemic palliative treatment. These stenoses should be relieved by
      local means in order to prevent the development of atelectasis and poststenotic
      pneumonia. Otherwise, patients will develop progressive dyspnea, and their
      general condition will decline rapidly. Various methods aimed at the relief of
      local obstructions exist and are often used in combination. Most procedures are
      performed under general anaesthesia using the rigid bronchoscope. Intraluminal
      obstructions can be relieved by laser-, cryo- and brachytherapy (endobronchial
      radiation). Extrinsic stenoses caused by airway compression from outside or by
      thickening of the airway wall through submucosal tumor growth must be dilated. At
      the end of these procedures, the insertion of silicone stents is ideally suited
      to maintain airway patency in dilated extrinsic stenoses and to prevent recurrent
      intraluminal tumor growth after laser therapy. The various methods aimed at the
      relief of malignant local airway obstructions are discussed, with emphasis on the
      recently developed silicone stents.

PMID- 1370589
TI  - [Respiratory problems in cancer--causes and treatment].
AB  - Half of the patients with advanced cancer suffer from shortness of breath. This
      may be due to the cancer itself, result from its treatment or arise from
      concurrent conditions. Careful assessment should precede any intervention.
      Treatment should be directed toward altering the underlying pathological process
      as far as possible (e.g. tumour reduction or pleural puncture). The relieve of
      symptoms by reassuring presence and morphine application are the mainstay, when
      it is not possible to reverse the cause of dyspnea, and can also successfully
      complement specific therapy.

PMID- 1370590
TI  - [Palliative medicine: symptomatic therapy as well as psychological and social
      care are in the foreground].

PMID- 1370591
TI  - [Interdisciplinary continuing education in palliative nursing, medicine and
      care].
AB  - Changing complementary goals in medicine, nursing and care pose new challenges to
      health professionals. The needs of the incurably ill or dying individuals and
      their relations are acknowledged more intensively again today. Quality of life
      and comprehensive care are corner-stones in the treatment and care of this group
      of patients. Realisation of the principles of palliative medicine and care
      demands a targeted approach to this multifaceted and burdening field. Nurses,
      doctors, social workers and other therapists have not yet been optimally prepared
      for this task. A common interdisciplinary training in this evolving field gives
      all the specialists from the different fields an opportunity for preparation to
      this task.

PMID- 1370592
TI  - Prostate cancer recurrence in radical surgery patients receiving autologous or
      homologous blood.
AB  - An evaluation of the effects of blood transfusion on recurrence and survival
      after radical surgery for prostate cancer was performed. Between 1982 and 1986,
      315 consecutive patients underwent radical retropubic prostatectomy by a single
      surgeon; of 309 patients for whom transfusion data were available, 94 received
      homologous blood (Group I) and 215 received autologous blood or no blood (Group
      II). At the time of surgery, there were no differences between Group I and Group
      II with respect to age, preoperative cancer stage, preoperative histologic grade
      (Gleason grade), prostatic acid phosphatase score, and preoperative potency. At
      discharge, the groups were similar in the status of neurovascular bundles,
      capsular involvement, seminal vesicle involvement, lymph node involvement,
      postoperative Gleason grade, and postoperative potency. No adjuvant hormone
      therapy or radiation therapy was administered until tumor recurrence. The
      patients were followed annually by physical examinations and measurements of
      prostate-specific antigen. Cancer recurrence was detected in 23 (24.5%) Group I
      patients and 49 (22.7%) Group II patients. These proportions were not
      significantly different in univariate or multivariate analysis, and the time to
      recurrence curves overlapped. It is concluded that homologous blood transfusions
      are not associated with more rapid tumor recurrence or death after radical
      surgery for prostate cancer than is seen with autologous transfusions. These
      results differ from previous reports, which suggested that transfusions may cause
      recurrence of cancer in patients with colorectal or prostate cancer because of
      the immunosuppressive effects of blood transfusions.

PMID- 1370593
TI  - Keratin expression in chemically induced mouse lung adenomas.
AB  - Chemically induced mouse lung tumors exhibit distinctive growth patterns,
      characterized by an alveolar or solid appearance, a papillary appearance, or a
      combination of the two. Lung tumors induced in strain A/J mice by either
      benzo(a)pyrene (BP) or by N-nitrosoethylurea (ENU) were examined for expression
      of low- and high-molecular-weight cytokeratins. Simple cytokeratins (low
      molecular weight) were found in all epithelial cells of the normal mouse lung and
      in all tumor types, whereas higher-molecular-weight cytokeratins were found only
      in normal bronchiolar cells and in papillary tumor cells. These data lend support
      to the hypothesis that chemically induced papillary lung tumors in strain A/J
      mice are derived from bronchiolar Clara cells.

PMID- 1370594
TI  - c-ets1 proto-oncogene is a transcription factor expressed in endothelial cells
      during tumor vascularization and other forms of angiogenesis in humans.
AB  - The c-ets1 proteins are transcriptional activators expressed within endothelial
      cells during blood vessel development in chick embryos. The authors show by in
      situ hybridization that c-ets1 is transcribed in the endothelia during
      angiogenesis in human embryos, in granulation tissue, and especially during tumor
      vascularization. c-ets1 mRNAs were also detected in the fibrocytes of tumor
      stroma and in the spindle cells of Kaposi's sarcomas, regarded as cells of
      endothelial origin. It has been shown that the c-ets proteins activate
      transcription through a PEA3 motif that plays a role in the stimulation of
      transcription of urokinase-type plasminogen-activator (u-PA), stromelysin and
      collagenase genes. The authors demonstrate in vitro that the angiogenic factor
      TNF alpha increases transiently the amount of both c-ets1 and u-PA mRNA in
      confluent human umbilical vein endothelial cells. Therefore, the authors suggest
      that the c-ets1 proteins might regulate the transcription of the genes coding for
      matrix-degrading proteases, which are necessary for both angiogenesis and tumor
      invasion.

PMID- 1370595
TI  - Appearance of ductular hepatocytes in rat liver after bile duct ligation and
      subsequent zone 3 necrosis by carbon tetrachloride.
AB  - Intrahepatic biliary cell plasticity was investigated in a rat model that
      combined prior bile ductular cell hyperplasia after bile duct ligation with
      subsequent CCl4-induced hepatonecrosis. Morphometric analysis of histologic liver
      sections from rats at 4 to 6 weeks after bile duct ligation and 3 to 5 days after
      CCl4 demonstrated the total section area to be occupied by near-equal amounts of
      hyperplastic bile ductular tissue area and hepatonecrotic area. Of particular
      significance was the unique presence, albeit infrequent, of newly appearing
      hepatic cell cholangioles composed of both biliary epithelial cells and one or
      more 'ductular hepatocytes' exclusively within the hyperplastic bile ductular
      tissue area of liver sections from the bile-duct-ligated/CCl4-treated rats, but
      not observed in control liver sections. This finding is compatible with the
      possibility of a 'transdifferentiation' of some hyperplastic biliary epithelial
      cells into 'ductular hepatocytes' in response to an extreme hepatic injury.

PMID- 1370596
TI  - Altered expression of proliferation and differentiation markers in human
      papillomavirus 16 and 18 immortalized epithelial cells grown in organotypic
      culture.
AB  - The patterns of expression of keratins K1 and K8, filaggrin, and the
      proliferation-associated protein, proliferating cell nuclear antigen (PCNA), were
      studied in normal and human papillomavirus (HPV) 16 or 18 immortalized
      keratinocyte cell lines grown on organotypic raft cultures. Normal keratinocytes
      produced an epithelial sheet that closely resembled epidermis in vivo,
      characterized by lack of K8 expression, PCNA expression restricted to the basal
      layer, and K1 and filaggrin expression in the suprabasal layers. Although
      morphologically abnormal in many respects, some HPV-immortalized cell lines
      produced cornified epithelial layers and approximated the normals in their
      patterns of expression of keratins and filaggrin. Other HPV-immortalized cell
      lines produced poorly differentiated epithelial layers that were characterized by
      loss of filaggrin expression, and the single tumorigenic cell line, 18-11, was
      distinguished by abundant K8 expression. All of the HPV-immortalized cell lines
      were distinguished from normal keratinocytes by a common pattern of full
      thickness PCNA expression in the epithelial layers they produced, suggesting that
      maintenance of the proliferative state may be an important contribution made by
      HPV 16 or 18 sequences toward the production of a malignant phenotype.

PMID- 1370597
TI  - Glycoprotein hormone alpha-subunit-producing pituitary adenomas in rats treated
      for one year with calcitonin.
AB  - Calcitonin, a calcium-lowering hormone, has been associated with an increased
      incidence of nonfunctioning pituitary tumors in rats. In this study, rats were
      treated with calcitonin (80 IU/kg/d) for 52 weeks. After treatment with
      calcitonin, immunohistochemistry and in situ hybridization analyses demonstrated
      that most pituitary tumors expressed the glycoprotein hormone alpha-subunit.
      Expression of the alpha-subunit was identified rarely in hyperplastic lesions of
      control animals. Serum levels of GH, PRL, ACTH, LH, and FSH were unchanged in
      calcitonin-treated rats relative to controls. However, TSH levels were increased
      2.1 fold after chronic treatment with calcitonin in both male and female rats (P
      less than 0.001). The level of glycoprotein hormone alpha-subunit was markedly
      increased (20-fold) in male rats with smaller elevations in female rats. Time
      course studies demonstrated that increases in serum alpha-subunit levels could be
      detected by 24 weeks of treatment and that elevations in alpha-subunit were
      present in the majority of animals by 40 weeks of treatment with calcitonin. The
      authors conclude that high doses of calcitonin, administered to rats for 6 months
      or longer, increases the incidence of alpha-subunit-producing pituitary tumors.

PMID- 1370598
TI  - Capsaicin desensitization inhibits cigarette smoke-induced increase in
      cytoplasmic motility of alveolar macrophages in guinea pigs.
AB  - To study effects of cigarette smoke on the cytoplasmic motility (CM) of alveolar
      macrophages (AM), we measured remanent field strength (RFS) in guinea pigs with
      and without systemic capsaicin pretreatment in vivo. Four days after instillation
      of 3 mg/kg ferrimagnetic particles (Fe3O4) into the trachea, RFS was measured at
      the body surface immediately after magnetization of the Fe3O4 particles by an
      externally applied magnetic field. RFS decreased with time because of particle
      rotation (relaxation), which is thought to be correlated to CM of AM. The initial
      relaxation curve was fitted to an exponential function. The relaxation rate
      (lambda 0) increased during cigarette smoke inhalation and returned to baseline
      values within 5 min, and with the inhalation of the smoke of as many as three
      cigarettes, peak lambda 0 increased in animals without capsaicin pretreatment.
      However, cigarette smoke decreased lambda 0 with an increased number of
      cigarettes in animals with capsaicin pretreatment. Injection of nicotine or
      acetylcholine increased respiratory resistance to a degree similar to that
      observed with cigarette smoke, but it did not change lambda 0. However, substance
      P (SP) increased lambda 0, and repeated administration of SP produced a
      significant tachyphylaxis in animals with and without capsaicin pretreatment in a
      fashion similar to that noted with cigarette smoke inhalation. Acrolein decreased
      lambda 0 in animals with and without capsaicin. Colchicine inhibited the
      cigarette smoke-induced increase in lambda 0.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370599
TI  - Regulation of CTP:phosphocholine cytidylyltransferase activity and
      phosphorylation in rat hepatocytes: lack of effect of elevated cAMP levels.
AB  - Immunoprecipitation of 32P-labeled CTP:phosphocholine cytidylyltransferase from
      freshly isolated rat hepatocytes followed by trypsin digestion and two
      dimensional peptide mapping revealed multiple phosphorylation sites. Treatment of
      the hepatocytes with 0.5 mM of the cAMP analog, 8-(4-chlorophenylthio)-adenosine
      3':5'-monophosphate or elevation of intracellular cAMP levels by cholera toxin
      activated the cAMP-dependent protein kinase activity in intact cells. Despite the
      activation of cAMP-dependent protein kinase no change in the rate of [3H]choline
      incorporation into phosphatidylcholine was detected. In addition, the activity of
      cytidylyltransferase in total cell homogenates and its distribution between
      soluble and particulate fractions remained unchanged. Comparison of peptide maps
      of 32P-labeled cytidylyltransferase obtained from control and cholera-toxin
      treated hepatocytes did not reveal any differences in the phosphorylation state
      of cytidylyltransferase. Furthermore, only [32P]phosphoserine residues were
      detected following phosphoamino acid analysis. We conclude that
      cytidylyltransferase activity is not altered solely by the activation of the cAMP
      dependent kinase in fresh hepatocytes.

PMID- 1370600
TI  - The ATP4- receptor-operated ion channel of human lymphocytes: inhibition of ion
      fluxes by amiloride analogs and by extracellular sodium ions.
AB  - Extracellular ATP is known to increase the membrane permeability of a variety of
      cells. Addition of ATP to human leukemic lymphocytes loaded with the Ca2+
      indicator, fura-2, induced a rise in cytosolic Ca2+ concentration which was
      attenuated or absent in NaCl media compared with KCl, choline Cl, or NMG Cl
      media. In contrast, anti-immunoglobulin antibody gave similar Ca2+ transients in
      NaCl and KCl media. A half-maximal inhibition of peak ATP-induced Ca2+ response
      was observed at 10-16 mM extracellular Na+. Basal 45Ca2+ influx into lymphocytes
      was stimulated 9.6-fold by ATP added to cells in KCl media, but the effect of ATP
      was greatly reduced for cells in NaCl media. Hexamethylene amiloride blocked 74%
      of the ATP-stimulated Ca45 uptake of cells in KCl media. Flow cytometry
      measurements of fluo-3-loaded cells confirmed that the ATP-induced rise in
      cytosolic Ca2+ was inhibited either by extracellular Na+ or by addition of
      hexamethylene amiloride. Extracellular ATP stimulated 86Rb efflux from
      lymphocytes 10-fold and this increment was inhibited by the amiloride analogs in
      a rank order of potency 5-(N-methyl-N-isobutyl)amiloride greater than 5-(N,N
      hexamethylene)amiloride greater than 5-(N-ethyl-N-isopropyl)amiloride greater
      than amiloride. ATP-induced 86Rb efflux showed a sigmoid dependence on the
      concentration of ATP and Hill analysis gave K1/2 of 90 and 130 microM and n
      values of 2.5 and 2.5 for KCl and NaCl media, respectively. However, the maximal
      ATP-induced 86Rb efflux was 3-fold greater in KCl than in NaCl media. Raising
      extracellular Na+ from 10 to 100 mM increased ATP-induced Na+ influx from a mean
      of 2.0 to 3.7 nEq/10(7) cells/min, suggesting either saturability or self
      inhibition by Na+ of its own influx. These data suggest that ATP opens a receptor
      operated ion channel which allows increased Ca2+ and Na+ influx and Rb+ efflux
      and these fluxes are inhibited by extracellular Na+ ions as well as by the
      amiloride analogs.

PMID- 1370601
TI  - Differential in vitro phosphorylation of clathrin light chains by the epidermal
      growth factor receptor-associated protein tyrosine kinase and a pp60c-src-related
      spleen tyrosine kinase.
AB  - The epidermal growth factor (EGF) receptor-associated protein tyrosine kinase
      activity has been suggested to play important roles in the EGF-enhanced, clathrin
      coated pit-mediated receptor internalization (W. S. Chen, C. S. Lazar, M. Peonie,
      R. Y. Tsien, G. N. Gill, and M. G. Rosenfeld, 1987, Nature 328, 820-823) but the
      kinase substrate important for this process has not been identified. This study
      demonstrates that the EGF receptor, partially purified from A431 epidermoid
      carcinoma cells, catalyzes the phosphorylation of one of the two clathrin light
      chains, clathrin light chain a (LCa). The phosphorylation activity is stimulated
      by EGF and immunoprecipitated by an EGF receptor monoclonal antibody. The
      phosphorylation occurs exclusively on tyrosine residues. Amino acid composition
      of the major tryptic phosphopeptide of the EGF receptor-phosphorylated LCa
      corresponds closely to that of residues 1 to 97 of LCa. A stoichiometry of 0.2
      mol phosphate/mol LCa was attained after 60 min at 30 degrees C and a Km value of
      1.7 microM was determined for the reaction. LCa of either neuronal or non
      neuronal origin could serve as a substrate. In addition to the EGF receptor
      tyrosine kinase, a particulate src-related protein tyrosine kinase purified from
      bovine spleen (C. M. E. Litwin, H.-C. Cheng, and J. H. Wang, 1991, J. Biol. Chem.
      226, 2557-2566) was shown in this study to also phosphorylate the light chains.
      However, in contrast to the EGF receptor phosphorylation, both clathrin light
      chains a and b were phosphorylated by the spleen kinase, suggesting that the two
      tyrosine kinases have differential site specificities. Given the specificity of
      LCa phosphorylation by the EGF receptor, we propose that LCa phosphorylation on a
      tyrosine residue(s) may be important in EGF-induced receptor internalization.

PMID- 1370602
TI  - Binding of transforming growth factor-beta 1 to immobilized human alpha 2
      macroglobulin.
AB  - Native alpha 2-macroglobulin (alpha 2M) and alpha 2M-methylamine were immobilized
      in 96-well microtiter plates. 125I-labeled transforming growth factor-beta 1 (TGF
      beta 1) bound to both alpha 2M variants; however, greater binding was observed
      with alpha 2M-methylamine. Binding of 125I-TGF-beta 1 (0.2 nM) to immobilized
      alpha 2M-methylamine was inhibited by nonradiolabeled TGF-beta 1 (up to 74% with
      0.4 microM TGF-beta 1). Approximately 10% of the TGF-beta 1-alpha 2M-methylamine
      complex was covalent. Treatment of alpha 2M-methylamine with iodoacetamide prior
      to immobilization completely eliminated covalent TGF-beta 1 binding; the total
      amount of 125I-TGF-beta 1-alpha 2M-methylamine complex detected was unchanged.
      The binding of 125I-TGF-beta 1 to immobilized alpha 2M-methylamine was not
      significantly inhibited by increasing the ionic strength to 1.0 M. Binding and
      complex dissociation were also unaffected by changes in pH within the range 6.9
      8.9. Acidic pH dramatically decreased binding and promoted complex dissociation;
      no binding of 125I-TGF-beta 1 to immobilized alpha 2M-methylamine was detected at
      pH 3.5. The interaction of TGF-beta 1 with immobilized alpha 2M-methylamine was
      not significantly changed by 1.0 mM EDTA or 1.0 mM CaCl2. ZnCl2 (1.0 mM)
      completely eliminated binding. This result was not due to TGF-beta 1
      precipitation or aggregation. Inhibition of 125I-TGF-beta 1 binding to alpha 2M
      methylamine was 50% complete (IC50) with 30 microM ZnCl2. Native alpha 2M,
      thrombospondin, and alpha 2M-methylamine (in solution) decreased binding of 125I
      TGF-beta 1 to immobilized alpha 2M-methylamine. The IC50 values for these three
      proteins were 520, 160, and 79 nM, respectively. The TGF-beta 1-binding activity
      of native alpha 2M may have reflected, at least in part, trace-contamination with
      alpha 2M-proteinase complex.

PMID- 1370603
TI  - Congenital choledochal dilatation with emphasis on pathophysiology of the biliary
      tract.
AB  - Of 37 patients with congenital choledochal dilatation, aged 8 days to 12 years,
      who had undergone excision with Roux-en-Y hepaticojejunostomy, 26 patients could
      be analyzed for morphologic abnormalities and pathophysiology of the biliary
      tract. Of the 26 patients with congenital choledochal dilatation, 25 (96.2%) had
      an abnormal choledochopancreaticoductal junction. Of the 12 patients with cystic
      type choledochal dilatation, 10 had the C-P type of abnormal
      choledochopancreaticoductal junction, and of the 13 patients with fusiform-type
      choledochal dilatation, nine had the P-C type. The amylase levels in the
      choledochal cyst and the gallbladder were elevated regardless of the form of
      choledochal dilatation. An adenocarcinoma in a cystic choledochal dilatation was
      found in one child. Therefore, longstanding inflammation of the biliary tract
      caused by the reflux of pancreatic juice might be one of the factors in
      carcinogenesis in the biliary tract. This free reflux of pancreatic juice was
      demonstrated not only by amylase levels in the biliary tract but also by
      intraoperative biliary manometry. This reflux might be explained by the lack of
      sphincter function at the junction of the common bile and pancreatic ducts.

PMID- 1370604
TI  - Inhibitory effect of HIV-1 envelope glycoproteins gp120 and gp160 on the in vitro
      growth of enriched (CD34+) hematopoietic progenitor cells.
AB  - The effect of increasing concentrations (from 0.01 to 10 micrograms/ml) of HIV-1
      envelope glycoproteins gp160, gp120, gp41 and core protein p24 was evaluated on
      the in vitro growth of enriched hematopoietic progenitors (CD34+ cells). Both
      gp120 and gp160, at concentrations from 0.01 to 10 micrograms/ml, caused a
      progressive and significant (p less than 0.05) decrease in viable CD34+ cell
      count in liquid cultures supplemented with 2 ng/ml of human recombinant (r)
      interleukin-3 (IL-3), evaluated by means of Trypan-blue exclusion and
      [3H]thymidine ([3H]TdR) incorporation. In the absence of rIL-3, no inhibitory
      effects were observed even at the highest gp160 and gp120 concentrations explored
      (10 micrograms/ml). On the contrary, gp41 and p24 did not affect the number of
      viable CD34+ cells, either in the presence or in the absence of rIL-3. Moreover,
      gp160 and gp120, but not gp41 and p24, significantly (p less than 0.05) inhibited
      the in vitro growth of granulomacrophage progenitors (CFU-GM) in a dose-dependent
      fashion. These data clearly demonstrate that HIV-1 envelope glycoproteins inhibit
      the growth of purified hematopoietic progenitors. We propose that HIV-1 can
      impair hematopoiesis through the interaction of gp120/gp160 with CD34+ cell
      surface, independently of an infectious process.

PMID- 1370606
TI  - Radiotherapy as a treatment for bladder cancer.

PMID- 1370605
TI  - Monoclonal antipeptide antibodies recognize epitopes upon VP4 and VP7 of simian
      rotavirus SA11 in infected MA104 cells.
AB  - To study morphogenetic events of rotavirus SA11-infected MA104 cells with
      strictly defined reagents we produced monoclonal antibodies against synthetic
      peptides from both outer capsid proteins VP4 (aa residues 228-241:
      QNTRNIVPVSIVSR) and VP7 (aa residues 319-326: SAAFYYRV) of simian rotavirus SA11.
      Two of the selected monoclonal antibodies proved to be reactive with determinants
      of SA11-infected MA104 rhesus monkey kidney cells, with purified SA11 as well as
      with the particular peptides used for immunization. The anti-VP4 antibody had a
      demonstrable neutralizing titer of 200 (50% focus reduction) whereas the anti-VP7
      MuMAb revealed no detectable neutralizing activity. In peptide-inhibition
      experiments, the corresponding peptide inhibited its MuMAb whereas the
      noncorresponding peptide had no effect on antibody binding to intracellular viral
      antigen. Localization of VP7 was preceded by VP4 as shown by immunofluorescence
      microscopy.

PMID- 1370607
TI  - Alteration of the kinetic properties of the epidermal growth factor receptor
      tyrosine kinase by basic proteins.
AB  - Previous studies have shown that lysine- and arginine-rich proteins can enhance
      the activity of tyrosine and serine/threonine protein kinases. However, the
      kinetics and mechanism of this activation are not fully understood. Therefore we
      investigated the ability of poly(amino acids) and the arginine-rich protein,
      protamine, to alter the kinetic properties of epidermal growth factor (EGF)
      receptor protein-tyrosine kinase activity using immunoaffinity-purified receptor
      isolated from human epidermoid carcinoma (A431) cells. Poly(L-lysine), poly(L
      arginine) and protamine stimulated EGF receptor kinase activity by 3-5-fold at
      non-saturating doses of ATP and peptide substrate, while poly(L-glutamate) had no
      effect. Initial kinetic studies demonstrated an increase in the maximum velocity
      and a decrease in the apparent Km for the peptide substrate angiotensin II in the
      presence of the basic effectors. Further analysis of the kinetic mechanism by
      product inhibition revealed that protamine altered the pattern of ADP inhibition
      towards the peptide substrate but not towards ATP. The change was indicative of
      the receptor's ability to form an enzyme-angiotensin II-ADP ternary complex in
      the presence of protamine but not in its absence. In addition, the basic
      effectors had a substantially decreased influence on the kinase activity of a C
      terminally truncated form of the EGF receptor. Thus the changes in kinase
      activity may be partially mediated by the C-terminal region of the receptor,
      which contains the sites of receptor self-phosphorylation. These results suggest
      that the basic domains of proteins can interact with the EGF receptor to induce
      changes in its kinetic properties, especially with regard to reactant recognition
      and binding.

PMID- 1370608
TI  - Retinoic acid stimulates expression of thrombomodulin, a cell surface
      anticoagulant glycoprotein, on human endothelial cells. Differences between up
      regulation of thrombomodulin by retinoic acid and cyclic AMP.
AB  - Thrombomodulin (TM) is a surface protein on endothelial cells, and represents one
      of the most valuable regulatory factors in the anticoagulant system. In this
      paper, we demonstrate that retinoic acid (RA) causes an increase in TM antigen on
      human umbilical vein endothelial cells (HUVECs) in vitro. The effect of RA on the
      surface TM level of HUVECs was dose-dependent in the range from 0.01 to 10 microM
      RA. Antigen levels began to increase 3 h after addition of 10 microM-RA, and
      plateaued at a maximum level of approx. 2.5 times that of the untreated control
      at 24 h. TM levels remained at a maximum for a further 12 h, and then gradually
      decreased. The effects of RA on cell surface TM activity and antigen levels were
      parallel in all experiments. TM expression was also increased by treatment with
      10 microM-retinal or 10 microM-retinol for 24 h, though the increases were
      approx. 70% and 30% respectively of that produced by 10 microM-RA. Pretreatment
      of HUVECs with cycloheximide inhibited the effect of RA. When HUVECs were
      incubated with both 10 microM-RA and 5 mM-8-bromo cyclic AMP (or 1 mM-3-isobutyl
      1-methylxanthine, a phosphodiesterase inhibitor), the increase in TM antigen was
      greater than that observed with either compound alone. Northern blot analysis
      showed that treatment of HUVECs with 8-bromo cyclic AMP, RA or RA plus 8-bromo
      cyclic AMP increased TM mRNA levels by 2.2-, 4.5- and 5.5-fold respectively
      compared with the untreated control. Furthermore, no significant difference in
      cellular cyclic AMP levels was observed between RA-treated and control cells.
      These results indicate that the expression of TM is not only controlled by the
      intracellular cyclic AMP level but is also affected by RA, and suggest that RA
      induced up-regulation of TM on HUVECs is independent of cyclic AMP regulation.

PMID- 1370609
TI  - Formation of nitric oxide hemoglobin in erythrocytes co-cultured with alveolar
      macrophages taken from bleomycin treated rats.
AB  - Alveolar macrophages, taken from rats treated with a single intratracheal dose of
      bleomycin, release reactive nitrogen intermediates in the form of nitric oxide
      which are cytostatic to murine leukemia L1210 cells. When cultured in the
      presence of erythrocytes the cytostatic activity of alveolar macrophages was
      inhibited which corresponded with an increase in nitrosylated hemoglobin content
      when compared with erythrocytes cultured alone. These results suggest that
      erythrocytes inhibit alveolar macrophage cytostatic activity by preventing
      reactive nitrogen intermediates from reaching target cells because the hemoglobin
      serves as a sink for reactive nitrogen intermediates in the form of nitric oxide.

PMID- 1370610
TI  - Interaction of estrogen receptor complexes with the promoter region of genes that
      are negatively regulated by estrogens: the alpha 2u-globulins.
AB  - Since estrogens strongly suppress the expression of alpha 2u-globulin genes in
      the rat liver, we studied the binding of estrogen-receptor complexes to fragments
      derived from alpha 2u-globulin gene RAO 01 using a DNA-cellulose competition
      assay. Rat uterus cytosol labelled with [3H]estradiol was used as a source of the
      estrogen receptor. As a positive control in these experiments we used an
      oligonucleotide containing the estrogen response element (ERE) cloned into pUC18.
      Our experiments indicate that estrogen-receptor complexes bind specifically to
      the ERE and to a fragment of RAO 01 located in the 5'-upstream region (bp -606 up
      to -575). This fragment is conserved among other members of this gene family.
      This is the first time that in vitro estrogen receptor binding is observed to
      gene fragments derived from a gene that is repressed by this steroid in vivo.

PMID- 1370611
TI  - Detection of thyrotropin-releasing hormone (TRH) mRNA by the reverse
      transcription-polymerase chain reaction in the human normal and tumoral anterior
      pituitary.
AB  - To investigate the presence of TRH mRNA in the human anterior pituitary tissue,
      total RNA from human normal and tumoral anterior pituitary, hypothalamus
      (positive control) and muscle tissues (negative control) was reverse transcribed
      (RT) to the first strand of cDNA. RT products were then amplified by polymerase
      chain reaction (PCR) using a set of three exon-specific primers (two external 5'
      and 3' primers and one internal 3' primer) for a target sequence of the TRH gene
      including an intronic sequence of about 650 base pairs (bp). Southern analysis of
      the RT-PCR products specifically hybridizing with a 45-mer TRH probe showed two
      bands of the predicted sizes (399 and 351 bp) far more intense in hypothalamus
      than in normal and tumoral anterior pituitary tissue. The 399 and 351 bp RT-PCR
      products contained the BglII enzyme restriction site included in the TRH cDNA
      sequences spanned by the primers and the two respective digested fragments which
      were, as predicted, 337 and 289 bp long, hybridized with the TRH probe. Based on
      these results, we can conclude that the RT-PCR products generated from RNA tissue
      were the target TRH sequences in the human normal and tumoral anterior pituitary
      tissue as well as in the hypothalamus. Our data imply TRH gene expression in the
      human anterior pituitary.

PMID- 1370612
TI  - Missense mutations and a deletion of the p53 gene in human gastric cancer.
AB  - To investigate the molecular pathogenesis of human gastric cancers the p53 gene,
      a suppressor oncogene, was analyzed in 12 human gastric cell lines. Southern blot
      and Northern blot analysis revealed a total deletion of p53 gene in KATO-III
      cells but no major abnormality of p53 gene in other cell lines. By the use of the
      reverse-transcriptase polymerase chain reaction and direct sequencing 7 cell
      lines showed point mutations of p53 gene resulting in amino-acid substitutions.
      Most of them were rare mutations which had not been observed in other types of
      cancers. One of these mutations was also detected through the use of PCR and
      oligomer-specific hybridization. Six out of 7 cell lines with mutations of p53
      gene also lost one allele of chromosome 17p. Immunoblotting of cell lysates with
      an antibody specific to p53 demonstrated the absence of p53 protein in KATO-III
      cell. By contrast, the high levels of the p53 protein were observed in 5 cell
      lines all of which contained mutations of p53 gene. These results further suggest
      that the inactivation of p53 gene may play an important role in the
      transformation of gastric cells to the malignant phenotype. KATO-III cells might
      be a good model for studying the significance of the loss of p53 gene in cellular
      transformation.

PMID- 1370613
TI  - Detection of point mutations in codon 331 of mitochondrial NADH dehydrogenase
      subunit 2 in Alzheimer's brains.
AB  - Point mutations in codon 331 of mitochondrial NADH dehydrogenase subunit 2 (ND2)
      were detected in 10 of 19 Alzheimer's brains but not in 11 normal brains. The
      same mutations were also detected in 2 of 6 patients with amyotrophic lateral
      sclerosis (ALS). However, neurofibrillary tangles and neuritic plaques
      characteristic of Alzheimer's disease were found histologically in the brain of
      one ALS patient who was positive of the mutation. The finding suggests that a
      point mutation in ND2 is a potential risk factor for Alzheimer's disease.

PMID- 1370614
TI  - Divergent effects of phorbol esters and insulin on insulin-like growth factor
      binding protein-1 (IGFBP-1) production and mRNA in rat H4IIE hepatoma cells.
AB  - 125I-IGF-I binding assay, western ligand and immunoblotting, and northern
      analysis of total RNA reveal that phorbol ester agonists of protein kinase C
      rapidly enhance IGFBP-1 production and increase the abundance of IGFBP-1 mRNA in
      rat H4IIE hepatoma cells. In combination with insulin, a potent inhibitor of
      IGFBP-1 gene transcription, this early effect of phorbol esters is dominant.
      These results demonstrate divergent regulation of IGFBP-1 by phorbol esters and
      insulin and indicate that protein kinase C may play a critical role in the
      regulation of IGFBP-1 and modulation IGF bioactivity in metabolic disease.

PMID- 1370615
TI  - Increased expression of retroviral sequences in progressionally advanced rat
      prostatic tumors.
AB  - Differential hybridization analysis revealed two cDNA clones, pBUS19 and pBUS30,
      to be overexpressed in progressionally advanced rat prostatic tumors. Northern
      blot analysis suggested the clones to be related although no homology in
      nucleotide sequence could be shown. Isolation and characterization of a pBUS19
      related clone, pJG116, and computer-assisted database comparison showed that all
      three clones could be mapped within a rat-specific endogenous retrovirus. The
      importance of overexpression of retroviral sequences in advanced prostatic cancer
      remains unclear.

PMID- 1370616
TI  - Activation of K+ current in macrophages by platelet activating factor.
AB  - Puff application of platelet activating factor (10(-8) M) onto peritoneal
      macrophages from thioglycollate-stimulated mice induced an outward current at a
      holding potential of -63 mV. The current was suppressed by an antagonist Y-24180
      but not by CV-3988. Charybdotoxin (10(-6) M) suppressed the current. Reversal
      potentials were dependent on external K+ concentrations. The current was not
      suppressed in Ca(2+)-free EGTA-containing solution but was completely abolished
      in BAPTA-AM containing solution. These results suggest that platelet activating
      factor activates a Ca(2+)-dependent K+ channel.

PMID- 1370617
TI  - Attachment of Trypanosoma cruzi to host cells: a monoclonal antibody recognizes a
      trypomastigote stage-specific epitope on the gp 83 required for parasite
      attachment.
AB  - A set of monoclonal antibodies against the purified surface gp 83 of T. cruzi
      trypomastigotes was produced and the ability of these monoclonals to inhibit the
      attachment of trypomastigotes to heart myoblasts was investigated. Western blots
      of solubilized trypomastigotes, epimastigotes or amastigotes probed with this set
      of monoclonal antibodies show that the gp 83 is present in invasive
      trypomastigotes, but not in non-invasive epimastigotes or amastigotes. One
      monoclonal antibody (Mab 4A4) from this set inhibits the attachment of
      trypomastigotes to heart myoblasts, whereas the others (MAbs 2H6, 4B9, 2D11) do
      not. These results show that the Mab 4A4 recognizes an epitope on the gp 83 of
      invasive trypomastigotes required for parasite binding to host cells.

PMID- 1370619
TI  - Detection of stromelysin and collagenase in synovial fluid from patients with
      rheumatoid arthritis and posttraumatic knee injury.
AB  - OBJECTIVE: To quantify stromelysin and collagenase in synovial fluid (SF) from
      patients with rheumatoid arthritis (RA) or traumatic knee injury. METHODS:
      Stromelysin and collagenase were measured in the SF of 33 patients with RA or
      posttraumatic knee injury, using specific double-antibody sandwich enzyme-linked
      immunosorbent assays. Stromelysin was fractionated from representative SF, and
      the molecular form was identified by immunoblot analysis. RESULTS: The
      stromelysin concentration was approximately 20-fold higher than the collagenase
      concentration in the fluids from patients with RA and approximately 8-fold higher
      in the fluids from patients with traumatic injury. For both metalloproteinases,
      there was a higher enzyme concentration in RA SF than in the SF from patients
      with trauma (stromelysin 40.1 +/- 26 micrograms/ml [mean +/- SD] in RA SF, 8.5 +/
      15 micrograms/ml in trauma SF; collagenase 2.2 +/- 3.3 micrograms/ml in RA SF,
      1.1 +/- 2.3 micrograms/ml in trauma SF). The majority of the stromelysin within
      the SF bound to reactive red-agarose and was identified as prostromelysin based
      on electrophoretic mobility and immunoblotting with monospecific antibodies.
      CONCLUSION: The finding of high levels of stromelysin in SF from patients with RA
      supports the proposal that this enzyme may play a role in the connective tissue
      degradation observed in this disease.

PMID- 1370618
TI  - Decreased accessory cell function and costimulatory activity by 1,25
      dihydroxyvitamin D3-treated monocytes.
AB  - To characterize the mechanism(s) by which 1,25-dihydroxyvitamin D3 (calcitriol)
      modulates the costimulatory capacity of monocytes, we examined the effect of
      calcitriol pretreatment of monocytes on their capacity to promote T cell
      proliferation (accessory cell function). Correlation of calcitriol-dependent
      changes in monocyte accessory cell function and alterations in phenotype and
      cytokine production, and the dependence of these changes on cell viability, were
      studied. Calcitriol pretreatment induced a defect in accessory cell function that
      was evident with fixed monocytes, suggesting a cell-surface-associated mechanism.
      Altered accessory cell function did not correlate with changes in HLA-DR antigen
      expression and was unaffected by concurrent treatment with interferon-gamma.
      Calcitriol treatment did not alter either the expression of adhesion molecules or
      monocytic production of interleukin-1 beta (IL-1 beta) or IL-6. Exogenous IL-1 or
      IL-6 did not overcome the impaired costimulatory activity of calcitriol-treated
      monocytes. Thus, calcitriol treatment reduces the capacity of monocytes to
      promote lectin-induced T cell activation at the level of the plasma membrane,
      perhaps through altered expression of an uncharacterized molecule important in
      monocyte-T cell interactions. At chronically inflamed sites, elaboration of
      calcitriol by activated macrophages may regulate the ability of monocytes to
      induce both antigen-dependent and antigen-independent T cell proliferation.

PMID- 1370620
TI  - Expression of cell-adhesion molecules in the salivary gland microenvironment of
      Sjogren's syndrome.
AB  - OBJECTIVE: The potential role of cell adhesion molecules in the pathogenesis of
      Sjogren's syndrome (SS) was assessed by examining their expression in salivary
      gland (SGL) tissue. METHODS: Intercellular adhesion molecule type 1 (ICAM-1),
      lymphocyte function-associated antigen type 1 (LFA-1), LFA-3, CD2, and CD44
      expression were determined using indirect immunofluorescence techniques. RESULTS:
      In inflamed labial SGL tissue, ICAM-1 expression was evident on infiltrating LFA
      1+/CD2+/LFA-3+ mononuclear cells, and to a limited extent on SGL acinar
      epithelial cells adjacent to sites of intense inflammation. CONCLUSION: In SS,
      the SGL microenvironment is characterized by only a modest up-regulation of ICAM
      1 expression on epithelial cells, despite the presence of T cells bearing an
      activated phenotype.

PMID- 1370621
TI  - Molecular genetic analysis of HLA-DR and HLA-DQ genes among anti-U1-70-kd
      autoantibody positive connective tissue disease patients.
AB  - OBJECTIVE: We have recently found that the presence of autoantibodies against the
      70-kd polypeptide of U1 RNP (U1-70-kd) is associated with HLA-DR4 and DR2. To
      further characterize this association, we performed a molecular genetic analysis
      of HLA-DR and DQ genes among patients with autoantibodies against U1-70-kd.
      METHODS: The polymerase chain reaction (PCR), sequence-specific oligonucleotide
      hybridization, and solid-phase direct DNA sequencing of PCR-amplified DNA were
      utilized to analyze HLA-DRB1, DRB5, DQA1, and DQB1 genes. RESULTS: A
      comprehensive analysis of HLA-DRB1, DRB5, DQA1, and DQB1 from 27 patients and
      controls identified shared amino acids FDYFYQA (Phe, Asp, Tyr, Phe, Tyr, Gln,
      Ala) at positions 26, 28, 30-32, 70, and 73 of HLA-DRB1 on disease-associated
      haplotypes. CONCLUSION: A common cluster of shared amino acids, or a shared
      epitope, identified within HLA-DRB1 among anti-U1-70-kd autoantibody positive
      connective tissue disease patients may be important in regulating an autoimmune
      response to the U1-70-kd antigen.

PMID- 1370622
TI  - Production of cyclodextrins, a novel carbohydrate, in the tubers of transgenic
      potato plants.
AB  - Cyclodextrins (CDs) are cyclic oligosaccharides containing six (alpha), seven
      (beta), or eight (gamma) glucose molecules, respectively. The cyclodextrin
      glycosyltransferases (CGT), which produce CDs from starch, are found only in
      bacteria and are used in batch fermentors with hydrolyzed starch to produce CDs
      commercially. Using a CGT gene from Klebsiella, we attempted to engineer the
      tubers of developing potatoes to produce these novel, high-value carbohydrates. A
      chimeric gene, consisting of (1) the patatin promoter for tuber-specific
      expression, (2) the small subunit of ribulose bisphosphate carboxylase (SSU)
      transit peptide for plastid targeting, (3) the CGT structural gene from
      Klebsiella and (4) the nopaline synthase 3' region, was introduced into potatoes.
      Both alpha and beta CDs were produced in tubers of transgenic potatoes at levels
      corresponding to 0.001-0.01% of the starch being converted to CDs.

PMID- 1370623
TI  - Physical properties of the Escherichia coli transcription termination factor rho.
      1. Association states and geometry of the rho hexamer.
AB  - To function as a DNA-RNA helicase in rho-dependent transcript termination, six
      genetically identical subunits of the Escherichia coli transcription termination
      protein rho must first assemble into a hexameric complex. To help determine the
      quaternary structure of this complex, we have studied the association equilibria
      of the rho protomers. Sedimentation equilibrium, sedimentation velocity,
      diffusion, X-ray scattering, and neutron-scattering data have been combined to
      create a "phase diagram" of the association states of this protein as a function
      of protein concentration and ionic environment. The results show that rho exists
      predominantly as a hexamer under approximately physiological conditions and that
      this hexamer is in equilibrium with both lower and higher states of association
      that may also have physiological relevance. Small-angle X-ray scattering
      measurements and theoretical calculations indicate that the rho hexamer has a
      radius of gyration of 50 +/- 3 A. The radius of gyration measured by small-angle
      neutron scattering in 2H2O is 47 +/- 3 A. These scattering studies also support
      earlier models of rho as a planar hexagon which have been developed on the basis
      of electron microscopy. In the following paper in this issue [Geiselmann, J.,
      Seifried, S. E., Yager, T. D., Liang, C., & von Hippel, P. H. (1992)], these
      results are combined with information on symmetry, subunit interactions, and
      packing geometry to obtain a model of the quaternary structure of the functional
      rho hexamer.

PMID- 1370624
TI  - Physical properties of the Escherichia coli transcription termination factor rho.
      2. Quaternary structure of the rho hexamer.
AB  - Under approximately physiological conditions, the transcription termination
      factor rho from Escherichia coli is a hexamer of planar hexagonal geometry
      [Geiselmann, J., Yager, T. D., Gill, S. C., Calmettes, P., & von Hippel, P. H.
      (1992) Biochemistry (preceding paper in this issue)]. Here we describe studies
      that further define the quaternary structure of this hexamer. We use a
      combination of chemical cross-linking and treatment with mild denaturants to show
      that the fundamental unit within the rho hexamer is a dimer stabilized by an
      isologous (or pseudoisologous) bonding interface. Three identical dimers of rho
      interact via a second type of isologous bonding interface to yield a hexamer with
      C3 or D3 symmetry. Cross-linking and denaturation experiments definitely rule out
      C6 and C2 symmetry for the rho hexamer. Data from fluorescence quenching,
      lifetime, and energy transfer experiments also argue against C2 symmetry. The
      simplest symmetry assignment that is not contradicted by any experimental data is
      D3; thus we conclude that the rho hexamer has D3 symmetry. We also consider the
      positioning of the binding sites for RNA and ATP relative to the coordinate
      reference frame of the D3 hexamer. Fluorescence energy transfer data are
      presented and integrated with data from the literature to arrive at a self
      consistent model for the quaternary structure of the rho hexamer.

PMID- 1370625
TI  - Catalytic domains of the LAR and CD45 protein tyrosine phosphatases from
      Escherichia coli expression systems: purification and characterization for
      specificity and mechanism.
AB  - The cytoplasmic domains of two human transmembrane protein tyrosine phosphatases
      (PTPases), LAR and CD45, have been expressed in Escherichia coli, purified to
      near-homogeneity, and compared for catalytic efficiency toward several
      phosphotyrosine-containing peptide substrates. A 615-residue LAR fragment (LAR
      D1D2) containing both tandemly repeated PTPase domains shows almost identical
      specific activity and high catalytic efficiency as the 40-kDa single-domain LAR
      D1 fragment, consistent with a single functional active site in the 70-kDa LAR
      D1D2 enzyme. A 90-kDa fragment of the human leukocyte CD45 PTPase, containing two
      similar tandemly repeated PTPase domains, shows parallel specificity to LAR-D1
      and LAR-D1D2 with a high kcat/Km value for a phosphotyrosyl undecapeptide.
      Sufficient purified LAR-D1 and LAR-D1D2 PTPases were available to demonstrate
      enzymatic exchange of 18O from 18O4 inorganic phosphate into H2(16)O at rates of
      approximately 1 x 10(-2) s-1. The oxygen-18 exchange probably proceeds via a
      phosphoenzyme intermediate. Brief incubation of all three PTPase fragments with a
      [32P]phosphotyrosyl peptide substrate prior to quench with SDS sample buffer and
      gel electrophoresis led to autoradiographic detection of 32P-labeled enzymes.
      Pulse/chase studies on the LAR 32P-enzyme showed turnover of the labeled
      phosphoryl group.

PMID- 1370626
TI  - Detection of substrates of keratinocyte transglutaminase in vitro and in vivo
      using a monoclonal antibody to dansylcadaverine.
AB  - A method providing more sensitive detection of transglutaminase substrates was
      developed to localize transglutaminase activity in tissue and to identify in vivo
      substrates in epidermal extracts. The enhanced sensitivity of this method was
      achieved via the generation of a monoclonal antibody (designated E7) made to
      dansylcadaverine. Transglutaminase substrates were visualized by western blot
      after a 1-min incubation with dansylcadaverine in contrast to the 2 h required
      when [14C]putrescine incorporation was measured by autoradiography of SDS
      polyacrylamide gels. In addition, putative substrates not apparent using
      conventional methods were readily detected by western analysis. An ELISA assay to
      measure transglutaminase activity showed similar sensitivity to the traditional
      radiometric assay (Lorand et al., 1972). The correlation between the ELISA
      procedure and the radiometric assay was high (r2 = 0.924). Strips of neonatal
      human and mouse skin incubated in dansylcadaverine-supplemented culture medium
      were used to localize enzyme activity and to detect substrates in vivo.
      Transglutaminase activity was demonstrated at the cellular periphery in the upper
      spinous and granular cell layers of the epidermis. Substrates detected in
      epidermal extracts were similar to those detected using the in vitro assay. This
      technique allows for highly sensitive and nonradiometric analysis of both
      enzymatic activity and the substrates involved. The extension of this methodology
      to an in vivo system is the first demonstration of a system in which the dynamics
      of cornified envelope assembly may be further studied.

PMID- 1370627
TI  - Contributions of phylogenetically variable structural elements to the function of
      the ribozyme ribonuclease P.
AB  - Ribonuclease P (RNase P) is a ribonucleoprotein enzyme which participates in
      processing precursor tRNAs. The RNA subunit contains the catalytic site and is
      capable of catalysis in the absence of the protein subunit. RNase P RNAs from
      various eubacteria consist of a core of conserved sequence and secondary
      structure which is evolutionarily modified in different organisms by the presence
      of discrete helical elements at various sites in the RNAs. The variable
      occurrence of these helical elements suggests that they have no important
      functional role in the enzyme. The Escherichia coli RNase P RNA contains four
      such elements. It has been shown that simultaneous deletion of all four of them
      produces an RNA that is functional but has several significant defects which
      could arise from general disruption of the RNA or from the loss of element
      specific functions. This paper describes a more detailed analysis of the role of
      the variable elements in E. coli RNase P RNA. Removal of one of the elements had
      no apparent effect on RNase P activity in vitro. Two other elements are required
      for correct folding of the RNA: their absence confers a requirement for extremely
      high monovalent salt concentrations, apparently to reduce intramolecular
      electrostatic repulsion. The fourth element that was tested participates in a
      long-range structural interaction (pseudoknot) which contributes to the
      structural stability of the enzyme and affects substrate binding affinity. In the
      absence of this helix, the RNA becomes temperature-sensitive, and the KM
      increases 100-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370628
TI  - Polyglutamylated alpha-tubulin can enter the tyrosination/detyrosination cycle.
AB  - We have previously identified a major modification of neuronal alpha-tubulin
      which consists of the posttranslational addition of a varying number of glutamyl
      units on the gamma-carboxyl group of glutamate residue 445. This modification,
      called polyglutamylation, was initially found associated with detyrosinated alpha
      tubulin [Edde, B., Rossier, J., Le Caer, J.P., Desbruyeres, E., Gros, F., &
      Denoulet, P. (1990) Science 247, 83-85]. In this report we show that a lateral
      chain of glutamyl units can also be present on tyrosinated alpha-tubulin.
      Incubation of cultured mouse brain neurons with radioactive tyrosine, in the
      presence of cycloheximide, resulted in a posttranslational labeling of six alpha
      tubulin isoelectric variants. Because both tyrosination and polyglutamylation
      occur in the C-terminal region of alpha-tubulin, the structure of this region was
      investigated. [3H]tyrosinated tubulin was mixed with a large excess of unlabeled
      mouse brain tubulin and digested with thermolysin. Five peptides, detected by
      their radioactivity, were purified by high-performance liquid chromatography.
      Amino acid sequencing and mass spectrometry showed that one of these peptides
      corresponds to the native C-terminal part of alpha-tubulin 440VEGEGEEEGEEY451 and
      that the remainders bear a varying number of glutamyl units linked to glutamate
      residue 445, which explains the observed heterogeneity of tyrosinated alpha
      tubulin. A quantitative analysis showed that the different tyrosinated forms of
      alpha-tubulin represent a minor (13%) fraction of the total alpha-tubulin present
      in the brain and that most (80%) of these tyrosinated forms are
      polyglutamylated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370629
TI  - Rotational diffusion of the erythrocyte integral membrane protein band 3: effect
      of hemichrome binding.
AB  - Human erythrocyte band 3 was covalently labeled within the integral membrane
      domain by incubating intact erythrocytes with the phosphorescent probe eosinyl-5
      maleimide. The rotational diffusion of band 3 in membranes prepared from these
      labeled cells was measured using the technique of time-resolved phosphorescence
      anisotropy. Three rotational correlation times ranging from 16 to 3800
      microseconds were observed, suggesting that band 3 exists in different aggregate
      states within the plane of the membrane. The oxidizing agent phenylhydrazine was
      used to induce hemichrome formation within intact erythrocytes. The
      immobilization of band 3 in membranes prepared from these erythrocytes suggests
      that the binding of hemichromes induces clustering of band 3. The addition of
      purified hemichromes to erythrocyte ghosts leads to a similar effect. We have
      also examined the mobility of the cytoplasmic domain of band 3. This region was
      labeled indirectly using a phosphorescently labeled antibody which binds to an
      epitope within the cytoplasmic domain. We observed very rapid motion of the
      cytoplasmic region of band 3, which was only partially restricted upon hemichrome
      binding. This suggests that the integral and cytoplasmic domains of band 3 may be
      independently mobile.

PMID- 1370630
TI  - Detergent solubilization of the endocytic Ca(2+)-independent hyaluronan receptor
      from rat liver endothelial cells and separation from a Ca(2+)-dependent
      hyaluronan-binding activity.
AB  - Rat liver sinusoidal endothelial cells (LECs) mediate the removal of hyaluronan
      (HA) from the circulation via a specific Ca(2+)-independent endocytic receptor.
      To characterize the receptor biochemically, detergent-soluble extracts were
      prepared from crude LEC membranes. Using a dot blot assay to quantitate 125I-HA
      binding activity in CHAPS-solubilized membranes, we detected not only specific
      Ca(2+)-independent but also specific Ca(2+)-dependent HA-binding activity. Both
      HA-binding activities behave as integral membrane-associated proteins; they are
      not released from LEC membranes by treatment at pH 11, and they require detergent
      for extraction. The Ca(2+)-independent HA receptor was inactivated by treatment
      at 56 degrees C for 30 min or with 200 mM DTT at 4 degrees C for 30 min, whereas
      the Ca(2+)-dependent activity actually increased by 75% after treatment at 56
      degrees C and only 20% of the Ca(2+)-dependent activity was lost after DTT
      treatment. A two-cycle membrane extraction protocol using CHAPS partially
      separated the two HA-binding activities. Eight millimolar KCl and 0.5% CHAPS
      extracted approximately 50% of the Ca(2+)-independent HA receptor, but only 4-11%
      of the Ca(2+)-dependent activity. When the KCl and CHAPS concentrations were
      increased to 2.0 M and 1.5%, respectively, the remaining HA receptor, as well as
      89-96% of the Ca(2+)-dependent activity, was then extracted. The Ca(2+)
      independent and Ca(2+)-dependent activities could also be further separated using
      Sephacryl S-400 gel filtration chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370631
TI  - Role of glucose carrier in human erythrocyte water permeability.
AB  - Although the transport properties of human erythrocyte water channels have been
      well characterized, the identity of the protein(s) mediating water flow remains
      unclear. Recent evidence that glucose carriers can conduct water raised the
      possibility that the glucose carrier, which is abundant in human erythrocytes, is
      the water channel. To test this possibility, water permeabilities and glucose
      fluxes were measured in large unilamellar vesicles (LUV) containing human
      erythrocyte lipid alone (lipid LUV), reconstituted purified human erythrocyte
      glucose carrier (Glut1 LUV), or reconstituted glucose carrier in the presence of
      other human erythrocyte ghost proteins (ghost LUV). In glucose and ghost LUV,
      glucose carriers were present at 25% of the density of native erythrocytes, were
      oriented randomly in the bilayer, and exhibited characteristic inhibition of
      glucose flux when exposed to cytochalasin B. Osmotic water permeability (Pf, in
      centimeters per second; n = 4) averaged 0.0012 +/- 0.00033 in lipid LUV, 0.0032
      +/- 0.0015 in Glut1 LUV, and 0.006 +/- 0.0014 in ghost LUV. Activation energies
      of water flow for the three preparations ranged between 10 and 13 kcal/mol; p
      (chloromercuri)benzenesulfonate (pCMBS), an organic mercurial inhibitor of
      erythrocyte water channels, and cytochalasin B did not alter Pf. These results
      indicate that reconstitution of glucose carriers at high density increases water
      permeability but does not result in water channel activity. However, because the
      turnover number of reconstituted carriers is reduced from that of native
      carriers, experiments were also performed on erythrocyte ghosts with intact water
      channel function. In ghosts, Pf averaged 0.038 +/- 0.013 (n = 9), while the
      activation energy for water flow averaged 3.0 +/- 0.3 kcal/mol.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1370632
TI  - Identification of the primer binding domain in human immunodeficiency virus
      reverse transcriptase.
AB  - We have labeled the primer binding domain of HIV1-RT with 5'-32P-labeled (dT)15
      primer using ultraviolet light energy. The specificity of the primer cross
      linking to HIV1-RT was demonstrated by competition experiments. Both synthetic
      and natural primers, e.g., p(dA)15, p(dC)15, and tRNA(Lys), inhibit p(dT)15
      binding and cross-linking to the enzyme. The observed binding and cross-linking
      of the primer to the enzyme were further shown to be functionally significant by
      the observation that tRNA(Lys) inhibits the polymerase activity on
      poly(rA).(dT)15 template-primer as well as the cross-linking of p(dT)15 to the
      enzyme to a similar extent. At an enzyme to p(dT)15 ratio of 1:3, about 15% of
      the enzyme can be cross-linked to the primer. To identify the domain cross-linked
      to (dT)15, tryptic peptides were generated and purified by a combination of HPLC
      on a C-18 reverse-phase column and DEAE-Sephadex chromatography. A single peptide
      cross-linked to p(dT)15 was identified. This peptide corresponded to amino acid
      residues 288-307 in the primary sequence of HIV1-RT as judged by amino acid
      composition and sequence analyses. Further, Leu(289)-Thr(290) and Leu(295)
      Thr(296) of HIV1-RT appear to be the probable sites of cross-linking to the
      primer p(dT)15.

PMID- 1370633
TI  - Tissue-specific and hormonal regulation of human prostate-specific glandular
      kallikrein.
AB  - Kallikreins are involved in the posttranslational processing of a number of
      specific polypeptide precursors. Previously, human glandular kallikrein (hGK-1)
      mRNA has been identified in the prostate; however, the hGK-1 protein has not been
      identified and characterized. Therefore, its physiologic function in the prostate
      is not known. In this study, we have isolated a full-length hGK-1 cDNA from a
      human adenocarcinoma cell line, LNCaP. In vitro translation experiments
      demonstrated that the molecular size of the hGK-1 protein generated from this
      cDNA is similar to that of prostate-specific antigen (PSA), a protein which is
      produced exclusively in the prostate. In situ hybridization with a hGK-1-specific
      oligonucleotide probe (77 bases), which can differentiate hGK-1 mRNA from PSA
      mRNA, demonstrated the hGK-1 mRNA to be located in the prostate epithelium. The
      hGK-1 mRNA was colocalized with PSA mRNA in prostatic epithelia. Moreover, in
      situ hybridization studies revealed that the level of hGK-1 mRNA in human benign
      prostatic hyperplasia tissues is approximately half that of PSA mRNA.
      Furthermore, we have demonstrated that hGK-1 mRNA is under androgenic regulation
      in LNCaP cells. Time course analysis revealed that hGK-1 mRNA levels increased
      significantly at 5 h of mibolerone treatment and reached maximal levels by 9 h.
      In addition, hGK-1 mRNA levels were increased by dihydrotestosterone, but not by
      dexamethasone or diethylstilbestrol treatments. Flutamide, a nonmetabolized anti
      androgen, repressed the androgenic effects. These studies suggest that expression
      of hGK-1 mRNA is regulated by androgen via the androgen receptor.

PMID- 1370634
TI  - Coculture of newborn rat skin epidermal cells with Swiss 3T3 cells: effect of the
      phases of 3T3 cells on attachment, growth and keratin synthesis of epidermal
      cells.
AB  - Swiss albino mouse 3T3 cells in various states were inoculated onto one side of
      Millipore filters. The other side of the filter was then coated with type I
      collagen and inoculated with newborn rat skin epidermal cells. On coculture of
      these cells, the attachment, growth and keratin synthesis of epidermal cells were
      found to depend on the state of the 3T3 cells: 3T3 cells in the stationary phase
      of growth were the most effective, followed by those in the logarithmic growth
      phase, those in the lag phase and plasmolyzed fibroblasts being only slightly
      effective. The effects of 3T3 cells in different states correlated well with
      their abilities to synthesize type IV collagen, but not type I collagen: with an
      increase in type IV collagen synthesis by the 3T3 cells, attachment of epidermal
      cells to the cell support, and their growth and synthesis of keratins increased.
      This culture system is concluded to mimic conditions in skin in vivo, and
      therefore to be suitable for studies on the effects of fibroblasts on the growth
      of epidermal cells.

PMID- 1370635
TI  - Localization of a PlA1 epitope to the amino terminal 66 residues of platelet
      glycoprotein IIIa.
AB  - A platelet glycoprotein (GP) IIIa epitope library was constructed by insertion of
      randomly cleaved GPIIIa cDNA fragments in the prokaryotic expression vector
      lambda gt22 and screened with purified anti-PlA1 antibodies for clones expressing
      a PlA1 epitope. Five independent clones were isolated and characterized by
      nucleotide sequencing. The smallest anti-PlA1 reactive clone obtained encoded the
      amino terminal 66 residues of mature GPIIIa. Substitution of leucine33 (PlA1)
      with a proline33 (PlA2) by in vitro mutagenesis resulted in the loss of anti-PlA1
      reactivity; however, this clone still reacted with anti-GPIIIa polyclonal
      antibodies. These data indicate that a PlA1 alloantigenic epitope is located
      within a small, unglycosylated fragment of GPIIIa containing the polymorphism
      responsible for the PIA phenotype. Furthermore, these results prove that small
      recombinant mimics of a PlA1 epitope may be synthesized and used for detection of
      these alloantibodies.

PMID- 1370636
TI  - Serotherapy of B-cell neoplasms with anti-B4-blocked ricin: a phase I trial of
      daily bolus infusion.
AB  - Anti-B4-blocked Ricin (Anti-B4-bR) is an immunotoxin comprised of the anti-B4
      monoclonal antibody (MoAb) and the protein toxin "blocked ricin." The anti-B4
      MoAb is directed against the B-lineage-restricted CD19 antigen expressed on more
      than 95% of normal and neoplastic B cells. Blocked ricin is an altered ricin
      derivative that has its nonspecific binding eliminated by chemically blocking the
      galactose binding domains of the B chain. In vitro cytotoxicity studies
      demonstrate that the IC37 of Anti-B4-bR is 2 x 10(-11) mol/L compared with 4 x
      10(-12) mol/L for native ricin. A phase I dose escalation clinical trial was
      conducted in 25 patients with refractory B-cell malignancies. Anti-B4-bR was
      administered by daily 1-hour bolus infusion for 5 consecutive days at doses
      ranging from 1 microgram/kg/d to 60 micrograms/kg/d. Serum levels above 1 nmol/L
      were achieved transiently in the majority of patients treated at the maximum
      tolerated dose of 50 micrograms/kg/d for 5 days for a total dose of 250
      micrograms/kg. The dose-limiting toxicity was defined by transient, reversible
      grade 3 elevations in hepatic transaminases, without impaired hepatic synthetic
      function. Minor toxicities included transient hypoalbuminemia, thrombocytopenia,
      and fevers. Human antimouse antibody and human anti-ricin antibody were detected
      in nine patients. One complete response, two partial responses, and eight mixed
      or transient responses were observed. These results show the in vitro and in vivo
      cytotoxicity of Anti-B4-bR and indicate that this immunotoxin can be administered
      as a daily bolus infusion for 5 days with tolerable, reversible toxicity.

PMID- 1370637
TI  - Role of c-kit ligand in the expansion of human hematopoietic progenitor cells.
AB  - To test the hypothesis that the c-kit ligand plays an important role in the
      regulation of early events occurring during human hematopoiesis, we determined
      the effect of a recombinant form of c-kit ligand, termed mast cell growth factor
      (MGF), on the high-proliferative potential colony-forming cell (HPP-CFC) and the
      cell responsible for initiating long-term hematopoiesis in vitro (LTBMIC). MGF
      alone did not promote HPP-CFC colony formation by CD34+ DR- CD15- marrow cells,
      but synergistically augmented the ability of a combination of granulocyte
      monocyte colony-stimulating factor (GM-CSF) interleukin (IL)-3 and a recombinant
      GM-CSF/IL-3 fusion protein (FP) to promote the formation of HPP-CFC-derived
      colonies. MGF had a similarly profound effect on in vitro long-term
      hematopoiesis. Repeated additions of IL-3, GM-CSF, or FP alone to CD34+ DR- CD15-
      marrow cells in a stromal cell-free culture system increased cell numbers 10(3)
      fold by day 56 of long-term bone marrow culture (LTBMC), while combinations of
      MGF with IL-3 or FP yielded 10(4)- and 10(5)-fold expansion of cell numbers.
      Expansion of the number of assayable colony-forming unit-granulocyte-monocyte
      (CFU-GM) generated during LTBMC was also markedly enhanced when MGF was added in
      combination with IL-3 or FP. In addition, MGF, IL-3, and FP individually led to a
      twofold to threefold increase in HPP-CFC numbers after 14 to 21 days of LTBMC.
      Furthermore, the effects of these cytokines on HPP-CFC expansion during LTBMC
      were additive. Throughout the LTBMC, cells receiving MGF possessed a higher
      cloning efficiency than those receiving IL-3, GM-CSF, or FP alone. These data
      indicate that the c-kit ligand synergistically interacts with a number of
      cytokines to directly augment the proliferative capacity of primitive human
      hematopoietic progenitor cells.

PMID- 1370638
TI  - Increased erythropoietin-receptor expression on CD34-positive bone marrow cells
      from patients with chronic myeloid leukemia.
AB  - Erythropoietin-receptor (EpR) expression on bone marrow cells from normal
      individuals and from patients with chronic myeloid leukemia (CML) was examined by
      multiparameter flow cytometry after stepwise amplified immunostaining with biotin
      labeled Ep, streptavidin-conjugated R-phycoerythrin, and biotinylated monoclonal
      anti-R-phycoerythrin. This approach allowed the detection of EpR-positive cells
      in all bone marrow samples studied. Most of the EpR-positive cells in normal bone
      marrow were found to be CD45-dull, CD34-negative, transferrin-receptor-positive
      and glycophorin-A-intermediate to -positive. This phenotype is characteristic of
      relatively mature erythroid precursors, ie, colony-forming units-erythroid and
      erythroblasts recognizable by classic staining procedures. Approximately 5% of
      normal EpR-positive cells displayed an intermediate expression of CD45,
      suggesting that these represented precursors of the CD45-dull EpR-positive cells.
      Some EpR-positive cells in chronic myeloid leukemia (CML) bone marrow had a
      phenotype similar to the major EpR-positive phenotype in normal bone marrow, ie,
      CD34-negative and CD45-dull. However, there was a disproportionate increase in
      the relative number of EpR-positive/CD45-intermediate cells in CML bone marrow.
      Even more striking differences between normal individuals and CML patients were
      observed when EpR-expression on CD34-positive marrow cells was analyzed. Very few
      EpR-positive cells were found in the CD34-positive fraction of normal bone
      marrow, whereas a significant fraction of the CD34-positive marrow cells from
      five of five CML patients expressed readily detectable EpR. These findings
      suggest that control of EpR expression is perturbed in the neoplastic clone of
      cells present in patients with CML. This may be related to the inadequate output
      of mature red blood cells typical of CML patients and may also be part of a more
      generalized perturbation in expression and/or functional integrity of other
      growth factor receptors on CML cells.

PMID- 1370639
TI  - Necessity of extracellular domain of W (c-kit) receptors for attachment of murine
      cultured mast cells to fibroblasts.
AB  - The receptor encoded by the W (c-kit) locus (W receptor) is expressed on the
      surface of cultured mast cells (CMC) derived from normal (+/+) mice, whereas its
      ligand encoded by the Sl locus (Sl ligand) is expressed on the surface of
      fibroblast cell lines derived from murine embryos. Involvement of W receptors and
      Sl ligands in attachment of CMC to fibroblasts was investigated. CMC were
      cocultured with fibroblasts; nonattaching CMC were removed and the remaining CMC
      were counted. CMC derived from mice of the W/W genotype did not express the
      extracellular domain of W receptors, and attachment of W/W CMC to +/+ fibroblasts
      was significantly impaired. Fibroblasts derived from embryos of the Sl/Sl
      genotype did not express Sl ligands, and the attachment of +/+ CMC to Sl/Sl
      fibroblasts was also impaired. The Wv and W42 alleles are point mutations at the
      intracellular tyrosine kinase domain. Attachment of either Wv/Wv, W/Wv, or W/W42
      CMC to +/+ fibroblasts was comparable with that of +/+ CMC. Moreover, the
      addition of monoclonal antibody against the extracellular domain of W receptors
      inhibited the attachment of +/+ CMC to +/+ fibroblasts. Thus, the extracellular
      domain of W receptors appeared to be necessary for attachment of CMC to
      fibroblasts.

PMID- 1370640
TI  - Myeloid and erythroid progenitor cells from normal bone marrow adhere to collagen
      type I.
AB  - One of the mechanisms by which normal hematopoietic progenitor cells remain
      localized within the bone marrow microenvironment is likely to involve adhesion
      of these cells to extracellular matrix (ECM) proteins. For example, there is
      evidence that uncommitted, HLA-DR-negative progenitor cells and committed
      erythroid precursors (BFU-E) bind to fibronectin. However, fibronectin is not
      known to mediate binding of committed myeloid (granulocyte-macrophage)
      progenitors, raising the possibility that other ECM proteins may be involved in
      this process. We investigated the binding of the MO7 myeloid cell line to a
      variety of ECM proteins and observed significant specific binding to collagen
      type I (56% +/- 5%), minimal binding to fibronectin (18% +/- 4%) or to laminin
      (19% +/- 5%), and no binding to collagen type III, IV, or V. Similarly, normal
      bone marrow myeloid progenitor cells (CFU-GM) demonstrated significant specific
      binding to collagen type I (46% +/- 8% and 47% +/- 12% for day 7 CFU-GM and day
      14 CFU-GM, respectively). The ability of collagen to mediate binding of
      progenitor cells was not restricted to the myeloid lineage, as BFU-E also showed
      significant binding to this ECM protein (40% +/- 10%). The binding of MO7 cells
      and CFU-GM was collagen-mediated, as demonstrated by complete inhibition of
      adherence after treatment with collagenase type VII, which was shown to
      specifically degrade collagen. Binding was not affected by anti-CD29 neutralizing
      antibody (anti-beta-1 integrin), the RGD-containing peptide sequence GRGDTP, or
      divalent cation chelation, suggesting that collagen binding is not mediated by
      the beta-1 integrin class of adhesion proteins. Finally, mature peripheral blood
      neutrophils and monocytes were also found to bind to collagen type I (25% +/- 8%
      and 29% +/- 6%, respectively). These data suggest that collagen type I may play a
      role in the localization of committed myeloid and erythroid progenitors within
      the bone marrow microenvironment.

PMID- 1370641
TI  - Flow cytometric assessment of human T-cell differentiation in thymus and bone
      marrow.
AB  - Using multidimensional flow cytometry we have defined and quantified the human T
      cell differentiation pathway, focusing on those events occurring among the most
      immature thymocytes and putative bone marrow (BM) T-precursors. Early thymocytes
      were found to express the CD34 antigen and consisted of a mean 1.2% of cells
      within human pediatric (n = 9) and 2.0% in fetal thymi (n = 4). All CD34+
      thymocytes were atypical blast by morphology, expressed intracytoplasmatic, but
      not cell surface, CD3, and were cell surface CD2+, CD5+, CD7+, CD38+, CD45+,
      CD45RA+, CD49d+, and LECAM-1(Leu8)high. CD34high thymocytes lacked surface
      expression of CD4 and CD8, but as CD34 expression diminished there was a
      coordinate increase in CD4 levels, followed by the appearance of CD8. The
      expression of CD1 and CD10 also increased concomitant with the loss of CD34,
      whereas expression of LECAM-1 diminished with CD34 downregulation. The
      differential expression of these antigens on early thymocytes (as well as the
      number of thymocytes displaying these patterns) was highly reproducible among the
      nine pediatric and four fetal specimens examined, suggesting a precise,
      stereotyped regulation of early differentiation events. Cell populations with
      antigen expression patterns suggestive of pluripotent stem cell (CD34high, CD38
      ), or non-T-lineage committed stem cells (CD34+, CD33+ or CD34+, CD19+) were not
      identified in either fetal or pediatric thymi (sensitivity = 1/10(4)). The
      presence of cells with the antigenic profile of the earliest CD34+ thymocytes was
      explored in human BM. Putative BM T-cell precursors with the appropriate
      phenotype (CD34+, CD7+, CD5+, CD2+, LECAM-1high) were readily identified in fetal
      specimens (constituting +/- 2% of the CD34+ population), but could not be
      reliably detected in adults. In contrast with thymi, only 13% of these cells
      expressed cytoplasmatic CD3, suggesting the presence of the immediate precursor
      of the putative prothymocyte population. This was further supported by the
      detection of CD34bright, CD7+, CD2-, CD5-, LECAM-1moderate cells in fetal
      specimens. Our results document the flow of cell surface differentiation during T
      lymphopoiesis and suggest that T-lineage features are first acquired in the BM.
      The ability to reproducibly identify and isolate T-cell precursor populations of
      precisely defined maturational stage in marrow and thymus by multiparameter flow
      cytometry will facilitate characterization of the molecular events controlling T
      lineage differentiation.

PMID- 1370642
TI  - Immunophenotyping and functional analysis of purified human uterine mast cells.
AB  - Human mast cells have been purified from uterine tissues, and their surface
      marker profile and function have been evaluated as part of ongoing studies of
      mast cell heterogeneity. Using a panel of antibodies, purified uterine mast cells
      (UMC; 81% +/- 7% purity, n = 10) were analyzed by immunofluorescence and flow
      cytometry for surface expression of various antigens. Consistent with previous
      analyses of mast cells from other tissues, UMC expressed HLA class I, IgE, c-kit
      receptor, CD9, CD33, CD43, CD45, and CD54, while CD11a, CD11b, CD14, CD16, CD23,
      and CD64 were not detected. Unlike other mast cells, UMC expressed CD11c/CD18
      (p150,95) and CD32 (Fc gamma RII). Additional antigens not previously studied on
      mast cells included the selectin LECAM-1 (Leu-8) and several beta 1 and beta 3
      integrins; expression of very late activation antigen-4 (VLA-4) (CD49d/CD29), VLA
      5 (CD49e/CD29), and the vitronectin receptor (CD51/CD61) was seen. Functional
      studies showed that treatment of human umbilical vein endothelial cells with
      interleukin-1 (5 ng/mL for 4 hours) resulted in a twofold to threefold increase
      in adhesiveness for UMC. Purification procedures did not alter histamine release
      responses to anti-IgE or the calcium ionophore A23187, and treatment of UMC with
      an anti-CD32 monoclonal antibody (IV.3) did not induce histamine release or alter
      anti-IgE-induced release. These data suggest that UMC may possess unique
      phenotypic characteristics, and support the concept of mast cell heterogeneity.

PMID- 1370643
TI  - Reactivity profiles of leukemic myeloblasts with monoclonal antibodies directed
      to sialosyl-Le(x) and other lacto-series type 2 chain antigens:absence of
      reactivity with normal hematopoietic progenitor cells.
AB  - We investigated the expression profiles of lacto-series type 2 antigens in
      hematopoietic cells and their progenitors, in comparison with leukemic
      leukocytes. Reactivity profiles of various anti-type 2 chain monoclonal
      antibodies (MoAbs) with leukemic blasts from 12 patients with acute myeloblastic
      leukemia (AML) and those from two patients with acute unclassified leukemia (AUL)
      show that anti-sialosyl-Le(x) MoAb SNH3 reacted strongly with greater than 95% of
      leukemic blast leukocyte populations from all patients (14 of 14). Another anti
      sialosyl-Le(x) MoAb, FH6, showed less reactivity than SNH3 (12 of 14 patients),
      while anti-Le(y) MoAb AH6 showed reactivity with only 8 of 14 patients. On the
      other hand, none of the anti-type 2 chain MoAbs reacted with CD34+ normal adult
      bone marrow (BM) mononuclear cells obtained independently from three healthy
      volunteers. MoAb SNH3, but not FH6 or AH6, showed complement-mediated
      cytotoxicity to leukemic blasts from these patients, as well as to myelogenous
      leukemia cell line HL60. Colony-forming unit granulocyte-macrophage (CFU-GM), but
      not burst-forming unit-erythroid (BFU-E), was incompletely inhibited by treatment
      of normal BM mononuclear cells with SNH3 and complement. The absence of type 2
      chain antigen expression in hematopoietic progenitor cells and in in vitro
      hematopoietic colonies (CFU-GM and BFU-E) strongly suggests that application of
      anti-carbohydrate MoAbs, particularly anti-sialosyl-Le(x) could be useful for
      elimination of leukemic myeloblasts infiltrating in BM, for purging of leukemic
      blasts in BM, and for facilitation of autologous BM transplantation.

PMID- 1370645
TI  - Membrane orientation of Rh(D) polypeptide and partial localization of its epitope
      containing domain.
AB  - We have previously shown that the effects of various enzyme treatments on Rh
      antigen-containing polypeptides in situ could be monitored by an antibody
      preparation which recognizes only these polypeptides following Western blotting.
      We now have prepared antibodies that specifically react with either the N- or C
      terminal ends of Rh-related proteins. Using all three, we have established that
      the C-terminus of Rh(D) polypeptide is at the cell surface, whereas its N
      terminal domain is situated at the cytoplasmic side of the red blood cell
      membrane. Chymotrypsin digestion of ghosts derived from (-D-/-D-) cells that are
      devoid of Rh (C/c) and (E/e) antigens produces three major Rh(D)-related
      fragments: the 20-Kd fragment contains the molecule's C-terminal domain, the 17
      Kd fragment its N-terminus, and the 13-Kd fragment neither. However, only the 17
      Kd fragment forms an immune-complex with human polyclonal anti-D, indicating that
      it contains the Rh(D) antigenic domain. Other findings presented here provide
      further evidence for a unique folding of Rh(D) polypeptide within the cell
      membrane and suggest that Rh(C/c) and (E/e) polypeptides, when present, may form
      complexes with it.

PMID- 1370644
TI  - Interactions of granulocyte-macrophage colony-stimulating factor (CSF),
      granulocyte CSF, and tumor necrosis factor alpha in the priming of the neutrophil
      respiratory burst.
AB  - Exposure of neutrophils to a range of cytokines augments their response to
      subsequent agonist-induced activation of the respiratory burst. We have examined
      the effects of several of these factors, both singly and in combination, on the
      priming of f-met-leu-phe (FMLP) and complement C5a-stimulated neutrophil H2O2
      production, using a whole blood flow cytometric assay designed to minimize
      artefactual activation. Both granulocyte-macrophage colony-stimulating factor (GM
      CSF) and tumor necrosis factor alpha (TNF alpha) produced a similar degree of
      priming of the FMLP-stimulated burst in vitro (558% +/- 86%, n = 41, and 581% +/-
      95%, n = 21, of the response seen with FMLP alone, respectively), but with
      markedly different kinetics (half-maximal response 20 minutes and 7 minutes,
      respectively). Preincubation with granulocyte colony-stimulating factor (G-CSF)
      alone caused only modest priming (202% +/- 39%, n = 14). Priming with cytokine
      combinations of the FMLP-stimulated burst showed that the combinations of G-CSF
      and TNF alpha and GM-CSF and TNF alpha are highly synergistic, with recruitment
      of neutrophils unresponsive to priming by single agents. Priming with the
      combination of GM-CSF and G-CSF was not significantly different to priming with
      GM-CSF alone. Similar results were obtained using C5a as the respiratory burst
      stimulus. Significant priming of the FMLP-stimulated respiratory burst was seen
      in vivo in patients receiving an infusion of GM-CSF (332% +/- 50% of preinfusion
      response to FMLP, P less than .005, n = 8). Priming was also seen in patients
      receiving G-CSF (152% +/- 58%, n = 5), although this did not reach conventional
      significance levels (.05 less than P less than .1). Although GM-CSF infusion
      caused priming in vivo, this was 48% less than predicted by preinfusion in vitro
      responses. This result was not due to inadequate GM-CSF levels as addition of
      further GM-CSF ex vivo did not correct the response. However, these neutrophils
      were still able to respond appropriately to ex vivo priming with TNF alpha, with
      a doubling in H2O2 production.

PMID- 1370646
TI  - Sequence variations in the 5' hypersensitive site-2 of the locus control region
      of beta S chromosomes are associated with different levels of fetal globin in
      hemoglobin S homozygotes.
AB  - We have compared the sequence of the 5' hypersensitive site-2 (5'-HS-2) of the
      locus control region (LCR) from a sickle cell anemia (SS) patient homozygous for
      haplotype 19 and with low levels of fetal hemoglobin (HbF), with the same
      sequence from an SS patient homozygous for haplotype 3 and with high levels of
      HbF. Several nucleotide variations were present in the 5'HS-2 of the haplotype 19
      individual. One is the A----G at position -10905 that creates an Sp1 binding site
      GCCCC (A----G)CCCC. A second is the T----G at position -10924 in a sequence that
      binds both erythroid and ubiquitous factors and exhibits high homology to the
      long terminal repeat of the Moloney leukemia viruses and Friend murine leukemia
      virus. Other differences were in the two AT-rich stretches of DNA, and an A----T
      substitution at position -10390. Dot-blot analyses of amplified DNA from several
      SS patients showed that these variations are specific for beta S chromosomes with
      haplotype 19. We also examined the 5'HS-2 sequence from an SS patient who is
      homozygous for haplotype 19, but has abnormally high levels of HbF (greater than
      20%). We observed a cross-over that has placed sequences similar to the 5'HS-2 of
      haplotype 3 in juxtaposition to the 5' flanking regions of haplotype 19. Thus, a
      beta S chromosome with haplotype 19 but having a 5'HS-2 (LCR) characteristic for
      haplotype 3 is associated with high gamma-chain expression. We postulate that
      factors produced under conditions of hematopoietic stress, together with genetic
      determinants on the haplotype 3-like LCR sequences, allow for high level
      expression of gamma-globin genes.

PMID- 1370647
TI  - Variation of HbF and F-cell number with the G-gamma Xmn I (C-T) polymorphism in
      normal individuals.

PMID- 1370648
TI  - The human prostatic carcinoma cell line LNCaP expresses biologically active,
      specific receptors for 1 alpha,25-dihydroxyvitamin D3.
AB  - The LNCaP prostatic carcinoma cell line was examined for the presence of specific
      receptors for 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3]. Whole cell
      binding studies identified approximately 2500 high-affinity (Kd = 1.4 x 10(-9)
      binding sites per cell. Competition studies revealed that these receptors are
      specific for the 1 alpha,25(OH)2 metabolite. Binding studies using the synthetic
      androgen R1881 indicate that separate androgen and vitamin D3 receptors exist in
      LNCaP cells. The vitamin D3 receptors sediment at approximately 3.5S on linear
      sucrose gradients. The sedimentation coefficient could be shifted with a
      monoclonal anti-vitamin D3 receptor antibody (9A7 gamma) but not with a
      monoclonal antibody to the androgen receptor (AN1-15). The receptor/ligand
      complex elutes from native DNA cellulose at 0.2 M KCl. Northern blot analysis
      identified an mRNA of approximately 4.6 kilobases which hybridized with a
      specific vitamin D3 receptor complementary DNA probe (hVDR). In the absence of
      androgens, 1 alpha,25(OH)2D3 stimulated growth and prostate-specific antigen
      production by LNCaP cells in a dose-dependent fashion. Dose-response curves
      indicated that at physiological concentrations (10(-9) M) 1 alpha,25(OH)2D3 was
      mitogenic, whereas at higher concentrations (10(-8) M) it promotes
      differentiation. These studies suggest that 1 alpha,25(OH)2D3 could play an
      important role in the natural history of and response to hormone therapy by
      prostatic cancer.

PMID- 1370649
TI  - Expression of simple epithelial cytokeratins in mouse epidermal keratinocytes
      harboring Harvey ras gene alterations.
AB  - Activation of a Harvey ras (H-ras) protooncogene is a frequent event associated
      with mouse epidermal carcinogenesis. We report that the transfection of a human H
      ras oncogene into an immortalized mouse epidermal cell line (MCA3D) induces the
      anomalous expression of cytokeratins (CKs) 8 and 18 characteristic of simple
      epithelia. The comparison of various transfectant cell clones indicated a direct
      correlation between the levels of CK8 expression and the mutated H-ras p21s. The
      expression of simple epithelial CKs is also described in cell lines derived from
      mouse skin carcinomas (HaCa4, CarC) and in keratinocytes transformed in vitro by
      a chemical carcinogen (PDV, PDVC57), all of which contain altered H-ras genes.
      The induction of CK8 and CK18 occurs at the mRNA level and, although both CK8 and
      CK18 mRNAs are expressed, CK18 protein does not accumulate whereas CK8 is
      incorporated into intermediate filaments. Immunofluorescence studies show that
      the pattern of CK8 protein expression is heterogeneous; some cells express very
      low amounts of CK8, whereas others synthesize relatively high levels of this
      protein. However, selection of strongly CK8-positive cells was found in one case
      where a more malignant population of cells (PDVC57) was derived by tumor
      transplantation of PDV. Our results suggest that activation of a H-ras gene can
      alter the normal differentiation program of epidermal cells and that the ability
      to synthesize CK8 and CK18 could be related to tumor progression.

PMID- 1370650
TI  - Synthesis and evaluation of fluoromycin: a novel fluorescence-labeled derivative
      of talisomycin S10b.
AB  - We have synthesized fluoromycin (FLM), a novel fluorescein-labeled derivative of
      talisomycin S10b (TLM S10b), and used it to evaluate cellular drug accumulation
      and distribution in bleomycin (BLM)-sensitive and -resistant cell lines. The
      fluorescence intensity of FLM was 300- to 400-fold greater than that of BLM A2,
      TLM S10b, or the lipophilic BLM analogue, liblomycin. FLM possessed an
      antiproliferative potency similar to liblomycin in BLM-sensitive human A-253
      squamous carcinoma cells but was less potent than BLM A2 or TLM S10b. C-10E
      cells, a clone of A-253 cells with 40- to 50-fold resistance to BLM A2 and TLM
      S10b, were 50-fold resistant to FLM. A partially revertant cell population (C-10E
      ND) regained sensitivity to BLM A2, TLM S10b, and FLM. FLM like BLM cleaved pGEM
      3Z plasmid DNA in vitro in a concentration-dependent manner. Flow cytometric
      analysis of FLM content in C-10E and C-10E ND cell lines showed 4-fold and 2-fold
      lower fluorescence intensity, respectively, compared with A-253 cells. Similar
      results were seen by fluorescence spectrophotometry with cell extracts.
      Fluorescence microscopy indicated heterogeneous distribution among A-253 cells
      with at least 50% of the cells exhibiting marked nuclear fluorescence
      localization. In contrast, C-10E cells displayed lower cellular fluorescence and
      predominantly cytoplasmic localization. C-10E ND cells exhibited a mixed
      population of nuclear and cytoplasmic vesicular localization with fluorescence
      levels that were intermediate between A-253 and C-10E cells. Thus, BLM-resistant
      cells have reduced levels of FLM and appear to have a lower nuclear:cytoplasmic
      ratio of FLM. FLM may be useful in studying the intracellular fate of BLM-like
      drugs as well as providing a tool to detect and isolate BLM-resistant cells.

PMID- 1370651
TI  - Protein-tyrosine phosphatase expression in pre-B cell NALM-6.
AB  - Protein-tyrosine phosphatase (PTP)-related complementary DNAs from NALM-6 (pre-B
      cell line) were amplified by reverse transcriptase polymerase chain reaction
      using primers corresponding to the conserved catalytic domains of PTPs. Thirty
      three polymerase chain reaction products, identified as PTP related complementary
      DNAs, were classified to RPTP-alpha, PTP1B, and 4 novel PTPs, which were
      designated as BPTP-1-4. Their expressions in NALM-6 and other cell lines were
      confirmed by Northern blot analysis. BPTP-1 and -2 exhibited extensive homology
      with the first and the second catalytic domains, respectively, of leukocyte
      common antigen related molecule (LAR) and human PTP delta. The transcriptional
      sizes of BPTP-1 and BPTP-2 are the same (7.2 kilobases) as that of LAR. The
      expression of BPTP-1 was abundant in lymphoid cell lines TALL-1 and NALM-6 but
      small in colon cell line BM314, which is in sharp contrast to the expression of
      LAR. These data suggest that the expression levels of BPTP-1 and LAR are altered
      in a cell specific manner, probably making them cell type associated PTPs.

PMID- 1370652
TI  - Altered expression of wild-type p53 tumor suppressor gene during murine
      epithelial cell transformation.
AB  - An epidermal cell model in which initiated, benign tumor-producing and carcinoma
      stages were derived from a cloned parental cell strain was used to examine p53
      expression during multistage epithelial carcinogenesis. Increased steady-state
      levels of p53 RNA were detected in squamous cell carcinomas compared to papilloma
      and normal epidermal cells. Nontumorigenic initiated cell precursors of the
      carcinomas exhibited normal p53 expression, localizing altered p53 regulation to
      the malignant conversion stage. Immunoprecipitation and Western immunoblot
      analyses demonstrated elevated levels of p53 protein in the moderately
      differentiated carcinoma compared to normal cells, and negligible levels of p53
      in the poorly differentiated carcinoma cells. Sequence analysis of p53
      complementary DNA from normal and carcinoma cells revealed no mutations in the
      coding or 5'- and 3'-untranslated regions, suggesting a novel mechanism of p53
      inactivation.

PMID- 1370653
TI  - In vivo transfer of the human cystic fibrosis transmembrane conductance regulator
      gene to the airway epithelium.
AB  - Direct transfer of the normal cystic fibrosis (CF) transmembrane conductance
      regulator (CFTR) gene to airway epithelium was evaluated using a replication
      deficient recombinant adenovirus (Ad) vector containing normal human CFTR cDNA
      (Ad-CFTR). In vitro Ad-CFTR-infected CFPAC-1 CF epithelial cells expressed human
      CFTR mRNA and protein and demonstrated correction of defective cAMP-mediated Cl-
      permeability. Two days after in vivo intratracheal introduction of Ad-CFTR in
      cotton rats, in situ analysis demonstrated human CFTR gene expression in lung
      epithelium. PCR amplification of reverse transcribed lung RNA demonstrated human
      CFTR transcripts derived from Ad-CFTR, and Northern analysis of lung RNA revealed
      human CFTR transcripts for up to 6 weeks. Human CFTR protein was detected in
      epithelial cells using anti-human CFTR antibody 11-14 days after infection. While
      the safety and effectiveness remain to be demonstrated, these observations
      suggest the feasibility of in vivo CFTR gene transfer as therapy for the
      pulmonary manifestations of CF.

PMID- 1370654
TI  - The N-terminal domains of acetylcholine receptor subunits contain recognition
      signals for the initial steps of receptor assembly.
AB  - Ligand-gated ion channels are oligomeric membrane proteins in which homologous
      subunits specifically recognize one another and assemble around an aqueous pore.
      To identify domains responsible for the specificity of subunit association, we
      used a dominant-negative assay in which truncated subunits of the mouse muscle
      acetylcholine receptor (AChR) were coexpressed with the four wild-type subunits
      in transfected COS cells. Fragments of the alpha, delta, and gamma subunits
      consisting solely of the extracellular N-terminal domain blocked surface
      expression of the AChR and the formation of alpha delta heterodimers, an early
      step in the assembly pathway of the AChR. Immunoprecipitation and sucrose
      gradient sedimentation experiments showed that an N-terminal fragment of the
      alpha subunit forms a specific complex with the intact delta subunit. Thus the
      extracellular N-terminal domain of the alpha, delta, and gamma subunits contains
      the information necessary for specific subunit association.

PMID- 1370655
TI  - The rat protein encoded by clone pp63 is a fetuin/alpha 2-HS glycoprotein-like
      molecule, but is it the tyrosine kinase inhibitor pp63?

PMID- 1370656
TI  - The binding site on ICAM-1 for Plasmodium falciparum-infected erythrocytes
      overlaps, but is distinct from, the LFA-1-binding site.
AB  - The intercellular adhesion molecule-1 (ICAM-1, CD54) is one of three putative
      endothelial receptors that mediate in vitro cytoadherence of P. falciparum
      infected erythrocytes. Since cytoadherence to postcapillary venular endothelium
      is thought to be a major factor in the virulence of P. falciparum malaria, we
      have examined the interaction between ICAM-1 and the P. falciparum-infected cell,
      and have compared it with the interaction to the physiological counter receptor,
      the leukocyte integrin LFA-1. Our results demonstrate that the malaria-binding
      site resides in the first two domains of the ICAM-1 molecule and overlaps, but is
      distinct from, the LFA-1 site.

PMID- 1370658
TI  - Transsphenoidal surgery for pituitary tumors.

PMID- 1370657
TI  - Pause transfer: a topogenic sequence in apolipoprotein B mediates stopping and
      restarting of translocation.
AB  - Previously, we described the stepwise translocation of a large amino-terminal
      fragment of apolipoprotein B (apo B15) in which the nascent secretory chain
      translocates through a series of distinct, nonintegrated transmembrane
      intermediates with large domains exposed to the cytoplasm. Thus, apo B15 appears
      to stop and restart translocation at several points. We have identified a
      sequence of amino acids in apo B15 that confers this behavior on a heterologous
      chimeric protein. In addition, we dissect pausing into two distinct steps,
      stopping and restarting, thereby trapping otherwise transient intermediates.
      Finally, we demonstrate the function of a second "pause transfer" sequence over
      200 amino acids downstream in apo B15 that restarts translocation
      posttranslationally, suggesting that multiple pause transfer sequences are
      involved in the biogenesis of apolipoprotein B.

PMID- 1370659
TI  - The role of gastric secretagogues in regulating gastric histamine release in
      vivo.
AB  - The effect of short-term intragastric arterial infusion of pentagastrin and
      methacholine on histamine and N tau-methyl histamine secretory rates was
      evaluated in mongrel dogs in vivo. Doses of pentagastrin and methacholine were
      chosen that stimulate gastric acid secretion equivalently. Histamine and N tau
      methyl histamine secretory rates were evaluated by measuring the arterial and
      gastric venous plasma histamine and N tau-methyl histamine concentrations at
      several time points during the secretagogue infusion, and gastric blood flow was
      continuously monitored. Histamine and N tau-methyl histamine plasma
      concentrations were analyzed by stable isotope dilution technique using gas
      chromatography/negative ion-chemical ionization mass spectrometry. Histamine and
      N tau-methyl histamine secretory rates were calculated by subtracting the
      arterial from the venous plasma concentrations and multiplying the difference by
      gastric plasma flow. Infusion of pentagastrin resulted in large pulsed increase
      of histamine release from 1.5 +/- 0.7 ng/min at time 0 to 72 +/- 20 ng/min at 5
      minutes, which decreased to a plateau of 20 +/- 8 ng/min at 20 minutes. N tau
      Methyl histamine secretory rate increased from 6.7 +/- 1.9 ng/min at baseline to
      a maximum of 42.5 +/- 13.1 ng/min at 10 minutes, and the increase was maintained
      for the duration of the pentagastrin infusion. Methacholine infusion was
      associated with a small but sustained increase in histamine release, from a
      baseline of 1.6 +/- 0.6 ng/min to 5.9 +/- 1.7 ng/min at 5 minutes. N tau-Methyl
      histamine secretory rate was unchanged by methacholine. Gastric blood flow
      changes to pentagastrin roughly paralleled the extent of histamine release, but
      methacholine is a gastric vasodilator in its own right. Our data indicate that
      pentagastrin is a much more effective stimulator of gastric histamine release
      than methacholine and that the overall role of histamine in gastrin-stimulated
      acid output is likely to be different from the role of histamine in cholinergic
      mediated gastric acid output.

PMID- 1370660
TI  - Peptide-containing neurons in different regions of the submucous plexus of human
      sigmoid colon.
AB  - Specimens of the sigmoid colon were obtained from male and female patients (n =
      11) with carcinoma of the colon or rectum and studied immunohistochemically for
      vasoactive intestinal polypeptide-, somatostatin-, substance P-, neuropeptide Y-,
      calcitonin gene-related peptide-, met- and leu-enkephalin-, 5-hydroxytryptamine-,
      and dopamine beta-hydroxylase-containing nerves. In the subdivisions of the
      submucous plexus (namely, Schabadasch's, Meissner's, and the intermediate
      plexuses), substance P- and vasoactive intestinal polypeptide-immunoreactive
      nerve fibers were the most numerous, and equal densities of these nerves were
      found in all three layers. In contrast, few neuropeptide Y-, met-enkephalin-, leu
      enkephalin-, calcitonin gene-related peptide-, somatostatin-, 5-hydroxytryptamine
      , and dopamine beta-hydroxylase-immunoreactive nerves were found in these
      regions. The nerve cell bodies of the submucous plexus contained vasoactive
      intestinal polypeptide, substance P, leu-enkephalin, somatostatin, and 5
      hydroxytryptamine but not neuropeptide Y, met-enkephalin, calcitonin gene-related
      peptide, and dopamine beta-hydroxylase. Vasoactive intestinal polypeptide
      containing nerve cell bodies were found in all three subdivisions. Substance P-,
      leu-enkephalin-, and somatostatin-immunoreactive nerve cell bodies were found in
      Schabadasch's plexus and the intermediate region of the submucous plexus, but
      they were absent from Meissner's plexus; 5-hydroxytryptamine-containing nerve
      cell bodies were only observed in Schabadasch's plexus. The possible function of
      the neuropeptide-, dopamine beta-hydroxylase-, and 5-hydroxytryptamine-containing
      neurons in the different layers of the submucous plexus is discussed.

PMID- 1370661
TI  - Evidence for continuous stimulation of interleukin-6 production in Crohn's
      disease.
AB  - Increased serum concentrations of acute-phase proteins can be found in active
      inflammatory bowel disease. Because interleukin 6 (IL-6) is one of the main
      mediators of acute-phase protein synthesis by the liver, the serum concentrations
      of IL-6 and the acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and
      alpha 1-acid glycoprotein were determined in 70 patients with Crohn's disease
      (CD) and 23 patients with ulcerative colitis (UC). Disease activities were
      determined by established clinical activity indices. Serum IL-6 concentrations
      were significantly (P less than 0.005) increased in patients with CD (mean +/-
      SEM, 6.8 +/- 0.9 U/mL) compared with patients with UC (mean, less than 4 U/mL)
      and healthy controls (mean, less than 4 U/mL). Of patients with CD, 68.5% had
      serum IL-6 concentrations of greater than or equal to 4 U/mL, compared with 21.7%
      of patients with UC and 0% of healthy controls. There was a tendency toward
      higher serum IL-6 concentrations in patients with active CD than in patients with
      inactive disease. However, these differences were not statistically significant.
      There was no correlation between IL-6 serum concentrations and clinical activity
      indices, possibly because of the short circulatory lifetime and rapid hepatic
      clearance of IL-6 from the portal venous blood. In contrast to serum IL-6, acute
      phase proteins, which have a longer circulatory lifetime, were significantly
      correlated with clinical activity indices. Only the follow-up of individual
      patients with initially highly active disease showed a further increase in IL-6
      levels during acute exacerbations of the inflammatory process. The results show
      that most patients with even moderately active CD have significantly increased
      serum concentrations of IL-6, most probably reflecting a continuous stimulation
      of IL-6-producing cells.

PMID- 1370662
TI  - Enhanced mucosal cytokine production in inflammatory bowel disease.
AB  - Proliferation, maturation, chemotaxis, and activation of neutrophils and
      monocytes are mediated largely by cytokines, including colony-stimulating factors
      and lymphokines. Cytokines produced in the intestinal mucosa contribute to the
      increased migration of neutrophils and monocytes into the lesion of inflammatory
      bowel disease and to the activation of these inflammatory cells. Lamina propria
      mononuclear cells isolated from colon tissue from 14 patients with inflammatory
      bowel disease (IBD) and from histologically normal controls were studied. Cells
      from IBD-affected tissue produced significantly more colony-stimulating factor
      activity (1402 +/- 252 U) per 2 x 10(6) cells than those from normal mucosa (362
      +/- 85 U), mainly because of the increased production of granulocyte colony
      stimulating factor and interleukin 1. This was accompanied by increases in the
      amount of specific messenger RNA for these two cytokines in lamina propria
      mononuclear cells from mucosa of patients with Crohn's disease (CD) compared with
      normal controls. By contrast, there was a substantial reduction in interleukin 3
      production in CD and in ulcerative colitis lamina propria mononuclear cells, and
      this was reflected in significantly reduced expression of interleukin 3 messenger
      RNA in CD cells. Of the agents used in the therapy of IBD, hydrocortisone and 5
      aminosalicylic acid, but not cyclosporin A, markedly suppressed in vitro
      production of cytokines by lamina propria mononuclear cells, suggesting that
      their therapeutic efficacy in vivo may be due in part to down-regulation of
      cytokine production in the inflamed mucosa.

PMID- 1370663
TI  - Soybean trypsin inhibitor and cerulein accelerate recovery of cerulein-induced
      pancreatitis in rats.
AB  - The role of exogenous and endogenous cholecystokinin has been studied in the
      process of pancreatic regeneration after acute pancreatitis. A mild form of
      pancreatitis was induced in rats by subcutaneous cerulein at 12 micrograms.kg-1,
      three times a day for 2 days. After 3 days of rest, the cerulein-treated rats
      were divided into four groups: rats with acute pancreatitis fed 20% casein, who
      received no treatment; rats fed 50% casein; rats fed 20% casein supplemented with
      1% soybean trypsin inhibitor (SBTI); and rats fed 20% casein who received 1
      microgram.kg-1 of subcutaneous cerulein, three times a day. Controls were fed 20%
      casein plus saline subcutaneously. Rats were killed after 5, 10, or 20 days of
      treatment. Pancreatitis resulted in significant decreases in pancreatic weight
      and contents of protein, amylase, chymotrypsin, RNA and DNA. During the
      regenerative process, 1 microgram.kg-1 of cerulein increased all parameters to
      control values within 5 days and induced pancreatic growth thereafter. SBTI
      restored the pancreas to normal after 10 days with cellular hypertrophy; the 50%
      casein diet gave a response similar to SBTI without hypertrophy. It can be
      concluded that cerulein and SBTI can accelerate pancreatic regeneration after an
      attack of acute pancreatitis.

PMID- 1370664
TI  - Expression of the Xanthomonas campestris pv. vesicatoria hrp gene cluster, which
      determines pathogenicity and hypersensitivity on pepper and tomato, is plant
      inducible.
AB  - The hrp gene cluster from Xanthomonas campestris pv. vesicatoria determines
      functions necessary not only for pathogenicity on the host plants pepper and
      tomato but also for the elicitation of the hypersensitive reaction on resistant
      host and nonhost plants. Transcriptional orientation and expression of the hrp
      loci were determined with hrp::Tn3-gus fusions. In addition, expression of the
      hrp loci was studied by RNA hybridization experiments. Expression of the hrp
      genes was not detectable after growth of the bacteria in complex medium or in
      minimal medium. However, high levels of induction of hrp gene expression were
      measured during growth of the bacteria in the plant. To search for a plant
      molecule responsible for this induction, we examined a variety of materials of
      plant origin for their ability to induce hrp gene expression. Filtrates from
      plant suspension cultures induced hrp genes to levels comparable to those induced
      in the plant. The inducing molecule(s) was found to be heat stable and
      hydrophilic and to have a molecular mass of less than 1,000 daltons.

PMID- 1370666
TI  - An immunochemical comparison of human myelin basic protein and its modified,
      citrullinated form, C8.
AB  - An immunochemical analysis was conducted to compare the C1 isomer of human myelin
      basic protein (MBP) with the newly described and less cationic, citrullinated
      isomer of MBP referred to as C8. Ten polyclonal antisera directed at multiple
      epitopes or restricted regions of MBP were used in radioimmunoassays to examine
      MBP-C1 and MBP-C8. Antisera reactive with MBP peptide 1-14 clearly distinguished
      MBP-C1 from MBP-C8. Antisera to human MBP peptides 10-19 and 90-170, but not to
      MBP peptide 69-89, showed modest differences between MBP-C1 and MBP-C8. The MBP
      C8s from multiple sclerosis (MS) and non-MS brain reacted essentially the same.
      With murine monoclonal antibodies and enzyme-linked immunosorbent assay (ELISA),
      differences between MBP-C8 and other isomers were shown for anti-MBP 10-19 but
      not for anti-MBP 1-9 or anti-MBP 80-89. These findings imply differences in
      sequence or conformation in the structure of MBP-C7 compared to MBP-C1, most
      notably near the amino terminus.

PMID- 1370665
TI  - The bvgAS locus negatively controls motility and synthesis of flagella in
      Bordetella bronchiseptica.
AB  - The products of the bvgAS locus coordinately regulate the expression of
      Bordetella virulence factors in response to environmental conditions. We have
      identified a phenotype in Bordetella bronchiseptica that is negatively controlled
      by bvg. Environmental signals which decrease (modulate) the expression of bvg
      activated genes lead to flagellum production and motility in B. bronchiseptica.
      Wild-type (Bvg+) strains are motile and produce peritrichous flagella only in the
      presence of modulating signals, whereas Bvg- (delta bvgAS or delta bvgS) strains
      are motile in the absence of modulators. The bvgS-C3 mutation, which confers
      signal insensitivity and constitutive activation of positively controlled loci,
      eliminates the induction of motility and production of flagellar organelles. The
      response to environmental signals is conserved in a diverse set of clinical
      isolates of both B. bronchiseptica and B. avium, another motile Bordetella
      species; however, nicotinic acid induced motility only in B. bronchiseptica.
      Purification of flagellar filaments from B. bronchiseptica strains by
      differential centrifugation followed by CsCl equilibrium density gradient
      centrifugation revealed two classes of flagellins of Mr 35,000 and 40,000. A
      survey of clinical isolates identified only these two flagellin isotypes, and
      coexpression of the two forms was not detected in any strain. All B. avium
      strains tested expressed a 42,000-Mr flagellin. Amino acid sequence analysis of
      the two B. bronchiseptica flagellins revealed 100% identity in the N-terminal
      region and 80% identity with Salmonella typhimurium flagellin. Monoclonal
      antibody 15D8, which recognizes a conserved epitope in flagellins in members of
      the family Enterobacteriaceae, cross-reacted with flagellins from B.
      bronchiseptica and B. avium. Our results highlight the biphasic nature of the B.
      bronchiseptica bvg regulon and provide a preliminary characterization of the Bvg
      regulated motility phenotype.

PMID- 1370667
TI  - Expression of Schwann cell and peripheral T-cell activation epitopes in
      hereditary motor and sensory neuropathy.
AB  - To evaluate possible immune-mediated mechanisms in hereditary motor and sensory
      neuropathy (HMSN-I, Charcot-Marie-Tooth syndrome), we examined class II major
      histocompatibility complex antigen expression (MHC-II, HLA-DR) in Schwann cells
      and peripheral lymphocyte T-cell (Ta1, CD26) activation in five unrelated adults
      with HMSN-I. Evidence of increased activation expression was found in both
      compartments but the pattern did not suggest a general state of hyperimmunity or
      appear related to clinical characteristics of HMSN. Significantly increased CD26+
      T-cell activation and greater than normal fluctuation of values occurred
      intermittently in sequential tests of eight HMSN patients and at single time
      points in 24 others. The combined data, consistent with repeated stimulations of
      an immune reaction under normal feedback control, suggest that HMSN-I expresses
      some characteristics also found in autoimmune polyneuropathies.

PMID- 1370668
TI  - Human astrocytes express membrane cofactor protein (CD46), a regulator of
      complement activation.
AB  - Expression of membrane cofactor protein (CD46) on cultured human astrocytes was
      demonstrated by indirect immunofluorescence microscopy and flow cytometry
      following staining with a monoclonal antibody specific for CD46. Western transfer
      and immunoblotting detected a doublet of Mr 66,000 and 56,000. Analysis of
      astrocyte mRNA revealed the presence of multiple alternatively spliced
      transcripts encoding different extracellular regions or cytoplasmic tails of
      CD46. Astrocytes were also shown to express decay accelerating factor, but not
      the type 1 complement receptor. Upregulation of astrocyte CD46 occurred following
      cytomegalovirus infection. These results indicate that astrocytes express
      proteins involved in regulation of complement activation and protection against
      autologous complement.

PMID- 1370669
TI  - Determination of the affinity of monoclonal human IgM for myelin-associated
      glycoprotein and sulfated glucuronic paragloboside.
AB  - We determined the association constant of eight monoclonal IgM with two of their
      targets, i.e. the myelin-associated glycoprotein (MAG) or the sulfated glucuronic
      paragloboside (SGPG). All IgM had a 10- to 100-fold higher affinity for MAG than
      for SGPG. The affinity of the different IgM for MAG ranged from 1.3 x 10(-6) to 7
      x 10(-9) mol/liter. The Scatchard plots for MAG were curvilinear, half of the
      sites being of high or low affinity. In contrast, the plots were linear in the
      assay using SGPG. No obvious correlations were found between the fine specificity
      of these IgM for the glucuronyl sulfate epitope and their affinity, although most
      IgM with a high affinity reacted exclusively with SGPG derivatives retaining a
      sulfate group. There was no parallelism between the severity of the neuropathy
      and the affinity of the IgM for MAG or SGPG.

PMID- 1370670
TI  - Astrocytes support mast cell viability in vitro.
AB  - Mast cells are normally found adjacent to blood vessels in the nervous system,
      and have been implicated in the development of inflammatory central nervous
      system (CNS) diseases such as experimental allergic encephalomyelitis. To further
      study mast cell-CNS interactions, we have developed a model in which viable rat
      peritoneal mast cells can be maintained in culture for up to 30 days on a
      monolayer of rat astrocytes. In this microenvironment, mast cells maintain their
      phenotype, morphology, and ability to degranulate in response to appropriate
      stimuli.

PMID- 1370671
TI  - Cerebrospinal fluid myelin basic protein as predictive marker of demyelination in
      AIDS dementia complex.
AB  - Myelin basic protein (MBP) was measured in cerebrospinal fluid (CSF) of patients
      with acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) in order to
      investigate the degree of white matter destruction. Results show that increased
      CSF levels of MBP were detected in all patients with severe ADC (10/10) and, less
      often, in subjects with mild (2/7) or moderate dementia (7/16). No evidence of
      MBP-elevated concentration was observed in 14 human immunodeficiency virus (HIV)
      seropositive subjects without neurological disorders and in nine HIV-seronegative
      controls. Our findings suggest that the measurement of CSF MBP concentration may
      represent a predictive marker of myelin injury and neurologic damage during the
      course of ADC.

PMID- 1370672
TI  - IgG monoclonal proteins from patients with axonal peripheral neuropathies bind to
      different epitopes of the 68 kDa neurofilament protein.
AB  - We describe three patients with a sensorimotor axonal polyneuropathy and an IgG M
      protein that binds to a 68 kDa axonal protein identified as the low molecular
      weight neurofilament protein (NF-L). The immunological studies revealed that the
      M-proteins have different target epitopes: one is phosphorylated and the other
      two are nonphosphorylated. One of the nonphosphorylated epitopes is common to
      other intermediate filaments, such as desmin and vimentin.

PMID- 1370673
TI  - Control of epidermal differentiation by a retinoid analogue unable to bind to
      cytosolic retinoic acid-binding proteins (CRABP).
AB  - The role played by cytosolic retinoic acid-binding proteins (CRABP) in the
      control of differentiation and morphogenesis by retinoids remains unclear, which
      contrasts with the presence of these binding proteins in tissues known to be
      targets for retinoic acid effects. Human epidermis represents a good system to
      address this question because 1) the effect of retinoids on keratinocyte
      differentiation is well documented; 2) epidermis contains CRABP, and the amount
      of these proteins is modulated both by keratinization and retinoids; 3) the
      architecture of epidermis obtained in vitro by growing adult human keratinocytes
      on a dermal substrate can be modulated by retinoids added to the culture medium
      in a dose-dependent manner; and 4) most markers of epidermal differentiation are
      also modulated by retinoids in a dose-dependent manner. In this study, we
      compared, in dose-response experiments, the biologic activities of retinoic acid
      and CD271, a substance unable to bind to CRABP, but able to bind to nuclear
      retinoic acid receptors (RAR). Our results show that retinoic acid and CD271
      exert similar controls on epidermal morphogenesis and keratinocyte
      differentiation, as shown by the inhibition of the synthesis of suprabasal
      keratins, filaggrin, and transglutaminase. Therefore, we exclude a qualitative
      role for CRABP in the control exerted by retinoids on the differentiation and
      morphogenesis of cultured human keratinocytes. Instead of being involved in the
      pathway via which retinoids control epidermal gene expression, CRABP might
      regulate the amount of intracellular-active retinoic acid and thus control
      quantitatively the intensity of biologic effects.

PMID- 1370674
TI  - Effects of topical retinoids on cytoskeletal proteins: implications for retinoid
      effects on epidermal differentiation.
AB  - In vivo effects of retinoids on epidermal differentiation were investigated by
      analyzing cytoskeletal proteins in rhino mice treated topically with all-trans
      retinoic acid (RA) and other retinoids (13-cis-retinoic acid, etretinate, TTNPB).
      Non-disulfide-linked cytoskeletal proteins, including keratins from the epidermal
      "living layers," were first selectively extracted using 9.5 M urea; subsequently,
      keratins of the stratum corneum were isolated using 9.5 M urea plus a reducing
      agent. Gel electrophoresis and immunoblot analysis showed that urea extracts of
      epidermis from vehicle-treated skin were composed predominantly of four major
      keratins (analogous to human epidermal keratins K1, K5, K10, and K14), and the
      keratin filament-associated protein filaggrin. In contrast, extracts of epidermis
      from retinoid-treated skin contained additional keratins (K6, K16, and K17) and
      almost no detectable filaggrin. Furthermore, similar analysis of stratum corneum
      keratins demonstrated that extracts from RA-treated skin did not contain the
      partially proteolyzed keratins typically observed in stratum corneum extracts of
      control animals. Hyperplasia-inducing agents (salicylic acid, croton oil) caused
      an increase in keratins K6, K16, and K17, but they did not effect filaggrin or
      alter proteolysis of stratum corneum keratins. The result that RA induced
      expression of keratins K6, K16, and K17, as commonly expressed in
      hyperproliferative epidermis, is consistent with the notion that retinoids
      increase epidermal cell proliferation in the basal and/or lower spinous layers.
      The findings that topical RA decreased filaggrin expression and reduced
      proteolysis of stratum corneum keratins, despite increased size and number of
      granular cells and the presence of an anucleate stratum corneum, suggest that
      topical RA may also modulate a later stage of epidermal differentiation involved
      in stratum corneum formation.

PMID- 1370675
TI  - Identification of pigment cell antigens defined by vitiligo antibodies.
AB  - Patients with vitiligo have circulating antibodies to pigment cells. To
      characterize this response further and to identify the antigens defined by
      vitiligo antibodies, sera of 23 patients with vitiligo and 22 patients with
      unrelated conditions were analyzed by immunoprecipitation and SDS-PAGE analysis
      of 125I-labeled cell antigens on pigment and control cells. Antibodies to pigment
      cell antigens were present in 18 (78%) of the patients with vitiligo but in only
      three (14%) of the control patients (p less than 0.05). The antibodies were
      directed to one or more antigens with molecular weight (MW) in kilodaltons (kD)
      of approximately 35, 40-45, 75, 90, or 150. The responses were most commonly
      directed to the 40-45-kD, 75-kD, and 90-kD antigens. Antibodies to these antigens
      were present in 74%, 57%, and 35% of vitiligo patients versus in 14%, 9%, and 0%
      of control individuals. The 35-kD and 90-kD antigens were preferentially
      expressed on human pigment cells, whereas the 40-45-, 75-, and 150-kD antigens
      were expressed on both pigment and control cells. These antigens were labeled by
      the lactoperoxidase technique, suggesting that they are cell surface antigens.
      These results confirm that antibodies to pigment cells are associated with
      vitiligo. These antibodies are directed to several cell surface antigens, some of
      which are preferentially expressed on pigment cells.

PMID- 1370676
TI  - Common pathogenetic pathways in allergic and irritant contact dermatitis.
AB  - Despite their different pathogeneses, allergic and irritant contact dermatitis
      show a remarkable similarity with respect to clinical appearance, histology, and
      immunohistology. To further analyze this apparent contradiction, our study was
      designed to meticulously compare cellular infiltrates in irritant and allergic
      patch-test reactions by immunostaining with a broad panel of monoclonal
      antibodies. For this purpose, skin biopsies from allergic and irritant patch-test
      reactions of similar inflammatory degree were obtained from the same probands. We
      found that after 72 h both types of reaction were characterized by an identical
      dermal infiltrate consisting mainly of memory T cells, many of which were
      activated, and macrophages. Dermal and epidermal Langerhans cell density and HLA-
      DR expression of keratinocytes were also virtually identical. Our results show
      that antigen recognition by specific memory T cells as well as irritants can
      finally induce the same pattern of inflammation, including activation of T cells
      obviously independent of exogenous antigen.

PMID- 1370677
TI  - Cytokeratin polypeptide profile of Merkel cells in human fetal and adult skin:
      difference of expression of cytokeratins in epidermal and dermal Merkel cells.
AB  - The origin of Merkel cells is uncertain, although current evidence by
      immunohistochemical keratin marker studies favors an epidermal derivation. We
      studied the expression of keratin species in Merkel cells of human fetus and
      adult using 19 anti-keratin antibodies. Epidermal and dermal Merkel cells
      contained not only simple epithelium-type but also some stratified epithelium
      type keratins. Interestingly, expression of some keratins was different between
      epidermal and dermal Merkel cells, for example, AN3 (50, 58 kD) and CKB1 (50 kD)
      recognized epidermal Merkel cells, but not dermal Merkel cells. These results
      suggest that surrounding keratinocytes influence the expression of cytokeratins
      in Merkel cells or that dermal Merkel cells undergo a modification from keratin
      producing epidermal Merkel cells to a more neural cell type by the association
      with nerve endings in the upper dermis. On the other hand, certain cytokeratin
      polypeptides recognizable with Ks19.1 (40 kD), CK5 (45 kD), and CAM5.2 (52.5 kD)
      were expressed in both epidermal and dermal Merkel cells. The expression of
      simple epithelium-type keratins in Merkel cells remained even after the epidermal
      basal cells gradually lost their expression.

PMID- 1370678
TI  - Recessive dystrophic epidermolysis bullosa phenotype is preserved in xenografts
      using SCID mice: development of an experimental in vivo model.
AB  - Recessive dystrophic epidermolysis bullosa (RDEB) is a subgroup of hereditary
      blistering diseases characterized by repetitive wounding and healing with
      subsequent extensive scarring. The purpose of this study was to establish a
      xenograft model that retains the RDEB phenotype and thus might be used as an
      experimental in vivo model to explore the molecular and biochemical mechanisms of
      the chronically wounded phenotype of RDEB. Full-thickness, tumor-free RDEB skin
      tissues were grafted onto the dorsum of severe combined immunodeficiency (SCID)
      mice. At 4, 8, 12, and 24 weeks after grafting, the xenografts were removed for
      examination. Immunofluorescence studies were performed using species-specific
      antibodies to human class I antigen, mouse class I antigen, human type IV and VII
      collagens and with cross-reacting antibody against bullous pemphigoid antigen
      (BPA). Staining with the antibody to human class I antigen, W6/32, and with the
      antibody to mouse class I antigen, 20.8.4s, confirmed the species-specific
      results obtained with the type IV and type VII collagen and laminin antibodies.
      The RDEB grafts showed essentially no staining with the type VII collagen
      antibody. Antibodies against laminin and BPA showed normal staining patterns in
      RDEB grafts. There was an overall paucity of anchoring fibrils in the grafts when
      examined with electron microscopy. Blisters could be induced in these grafts with
      minor trauma and showed a sublamina densa separation by immunomapping and
      electron microscopy. As late as 24 weeks post-transplantation, the RDEB grafts
      remain human, are not significantly replaced by mouse cells, and retain the RDEB
      disease phenotype.

PMID- 1370679
TI  - CD28 interaction with B7 costimulates primary allogeneic proliferative responses
      and cytotoxicity mediated by small, resting T lymphocytes.
AB  - Engagement of the CD3/T cell antigen receptor complex on small, resting T cells
      is insufficient to trigger cell-mediated cytotoxicity or to induce a
      proliferative response. In the present study, we have used genetic transfection
      to demonstrate that interaction of the B7-BB1 B cell activation antigen with the
      CD28 T cell differentiation antigen costimulates cell-mediated cytotoxicity and
      proliferation initiated by either anti-CD2 or anti-CD3 monoclonal antibody (mAb).
      Moreover, a B7-negative Burkitt's lymphoma cell line that fails to stimulate an
      allogeneic mixed lymphocyte response is rendered a potent stimulator after
      transfection with B7. The mixed leukocyte reaction proliferative response against
      the B7 transfectant is inhibited by either anti-CD28 or B7 mAb. We also
      demonstrate that freshly isolated small, resting human T cells can mediate anti
      CD3 or anti-CD2 mAb-redirected cytotoxicity against a murine Fc receptor-bearing
      mastocytoma transfected with human B7. These preexisting cytotoxic T lymphocytes
      in peripheral blood are present in both the CD4 and CD8 subsets, but are
      preferentially within the CD45RO+ "memory" population. While small, resting T
      cells apparently require costimulation by CD28/B7 interactions, this requirement
      is lost after T cell activation. Anti-CD3 initiates a cytotoxic response mediated
      by in vitro cultured T cell clones in the absence of B7 ligand. The existence of
      functional cytolytic T cells in the small, resting T cell population may be
      advantageous in facilitating rapid responses to immune challenge.

PMID- 1370680
TI  - Genetic modulation of antigen presentation by HLA-B27 molecules.
AB  - In studies of antigenic peptide presentation, we have found a healthy volunteer
      whose lymphoblastoid cells were unable to present three different virus-derived
      epitopes to cytotoxic T lymphocytes (CTL) despite expressing the correct
      restricting HLA-B27 molecules on the cell surface. B cell lines were established
      from other members of the donor's family, including individuals suffering from
      ankylosing spondylitis and related diseases, and were tested for their ability to
      function as target cells in the same assay. None of the eight B cell lines that
      expressed HLA-B27 presented a known peptide epitope to CTL. However, cells from a
      family member that expressed HLA-B8 could present an epitope peptide restricted
      by that molecule. The B27 molecule in this family proved to be the B2702 subtype
      on isoelectric focusing gels, appearing in exactly the same position as B2702
      from other cell lines that did present the peptide. To exclude mutations
      resulting in noncharged amino acid substitutions, cDNA coding for B2702 was
      cloned from the proband's cell line and sequenced. No coding changes were found.
      The cloned cDNA was transfected into HLA-A- and B-negative HMy/C1R cells, and the
      B2702 molecules generated in this environment rendered these cells, after
      incubation with peptide, susceptible to lysis by peptide-specific CTL. These data
      are compatible with the presence of a factor(s), possibly HLA linked, interfering
      with antigen presentation by otherwise normal B2702 molecules in this family.

PMID- 1370681
TI  - Profilins constitute a novel family of functional plant pan-allergens.
AB  - Type I allergy is a major health problem in industrialized countries where up to
      15% of the population suffer from allergic symptoms (rhinitis, conjunctivitis,
      and asthma). Previously, we identified a cDNA clone that encoded a birch pollen
      allergen as profilin. Profilins constitute a ubiquitous family of proteins that
      control actin polymerization in eukaryotic cells; in particular, profilin
      participates in the acrosomal reaction of animal sperm cells. Although profilins
      had been unknown in plants so far, our finding led to the assumption that
      profilins might have similar functions in pollens during plant fertilization and
      therefore represent allergenic components in almost all pollens. We show that
      profilins are prominent allergens that can be isolated from tree pollens (Betula
      verrucosa, birch), from pollens of grasses (Phleum pratense, timothy grass), and
      weeds (Artemisia vulgaris, mugwort). About 20% of all pollen allergic patients
      tested (n = 65) displayed immunoglobulin E (IgE) reactivity to recombinant birch
      profilin that was expressed in pKK223-3. An IgE inhibition experiment performed
      with recombinant birch profilin and purified natural profilins from timothy grass
      and mugwort indicates common IgE epitopes. Moreover, all pollen profilins
      purified from these far distantly related plant species, and likewise the
      purified recombinant birch profilin, are able to elicit dose-dependent histamine
      release via high affinity Fc epsilon receptor of blood basophils from profilin
      allergic patients. The presence of profilin and possibly related proteins as
      crossreacting allergenic components in various plants therefore provides an
      explanation as to why certain allergic patients display type I allergic reactions
      with pollens and even food from distantly related plants. A functional pan
      allergen, like profilin, available as purified recombinant protein, may be a
      useful diagnostic and probably therapeutic reagent.

PMID- 1370682
TI  - Mutations defining functional regions of the superantigen staphylococcal
      enterotoxin B.
AB  - Staphylococcal enterotoxin B (SEB) is both a superantigen and toxin. As a
      superantigen, SEB can bind to major histocompatibility complex (MHC) class II
      molecules to form a ligand for alpha/beta T cell receptors bearing particular V
      beta elements. As a toxin, SEB causes rapid weight loss in mice sometimes leading
      to death. We show here that both of these functions map to the NH2-terminal
      portion of the toxin. Three regions were identified: one important in MHC class
      II binding, one in T cell recognition, and one in both functions. These results
      support the conclusion that the toxicity of SEB is related to massive T cell
      stimulation and release of cytokine mediators and show that the residues
      interacting with MHC and the T cell receptor are intertwined.

PMID- 1370683
TI  - The human fetal omentum: a site of B cell generation.
AB  - The fetal mouse omentum has been shown to be a source of precursors that
      exclusively reconstitutes Ly1+ B cells and the closely related Ly1- sister
      population, but not conventional B cells or T cells. We have extended these
      studies to compare B cell development in the human fetal omentum, liver, and
      spleen, and to demonstrate that the pro/pre-B cell compartment (CD24+, sIgM-) is
      detected in the omentum and liver but not spleen as early as 8 wk of gestation.
      From 8 to 12 wk of gestation, the proportions of IgM+ cells that were pre-B cells
      (cIgM+/sIgM-) in the omentum and liver were 53 +/- 15% and 45 +/- 13%,
      respectively, and IgM+ cells were not detectable in the spleen. After 12 wk, the
      percentage of pre-B cells was unchanged in the fetal liver (41 +/- 10%) but
      decreased significantly in the omentum (25 +/- 14%); pre-B cells were now
      detected in the spleen but at much lower percentages (2 +/- 3%) than either the
      omentum or liver. The nuclear enzyme, Tdt, was detected in approximately 25% of
      the CD24+ cells in the omentum and liver during the 8-12-wk time period, however,
      Tdt+ cells were not detected in the spleen. Approximately 40% of the mature B
      cells found in the omentum and spleen were CD5+ compared with only 20% in the
      liver. These results demonstrate that the fetal omentum, like the fetal liver and
      bone marrow, is a primary site of B cell development.

PMID- 1370684
TI  - Identification of HLA-DR1 beta chain residues critical for binding staphylococcal
      enterotoxins A and E.
AB  - Superantigens are thought to make external contacts with major histocompatibility
      complex (MHC) class II molecules and with the V beta portion of a T cell antigen
      receptor (TCR), thereby stimulating entire families of T cells. The precise
      mapping of superantigen binding sites on class II molecules may provide valuable
      information on how TCR and MHC molecules interact. Two bacterial superantigens,
      staphylococcal enterotoxins A and E (SEA/SEE) bind well to most HLA-DR alleles,
      but poorly to HLA-DRw53. The sequences responsible for this binding were
      localized to the putative alpha helix of the DR beta chain by measuring toxin
      binding to a panel of chimeric class II molecules expressed on transfected cells.
      Binding of SEA/SEE to the DRw14 (Dw9) molecule suggested that the conserved
      histidine 81 in the beta chain of most DR molecules was important, whereas the
      tyrosine 81 in the DRw53 beta chain was detrimental for high-affinity binding. To
      prove this, reciprocal point mutations were introduced in the DR1 and DRw53 beta
      chains. Mutation of histidine 81 in the DR1 beta chain to tyrosine reduced
      SEA/SEE binding, but did not prevent recognition of two DR1-restricted peptides
      by six of eight antigen-specific T cell lines. Conversely, introduction to
      histidine at position 81 in the DRw53 beta chain restored normal levels of
      SEA/SEE binding. These data suggest that a binding site of SEA and SEE lies on
      the outer face of the beta chain alpha helix, pointing away from the antigen
      binding groove.

PMID- 1370685
TI  - cis and trans elements differ among mouse strains with high and low extrahepatic
      complement factor B gene expression.
AB  - Factor B (Bf), an enzyme of the alternative pathway of complement activation, is
      one of four major histocompatibility complex (MHC) class III genes. To ascertain
      the genetic mechanism for tissue-specific constitutive and regulated expression
      of Bf, we sequenced the regulatory regions 5' of the gene from mice of different
      H-2 MHC haplotypes and assessed trans-acting factors, specific DNA binding
      nucleoproteins, in liver and kidney. Striking tissue-specific differences in
      constitutive expression of Bf were demonstrated in mice of H-2f or H-2z
      haplotypes when compared with H-2d or H-2u (kidney and intestinal Bf in H-2d or H
      2u much greater than H-2f or H-2z). These differences correlated with a point
      nucleotide substitution 3 bp downstream of the upstream Bf initiation site that
      affects interaction with a DNA binding protein. This and additional cis
      differences localize the sequence substitutions responsible for previously
      identified restriction fragment length polymorphisms among inbred mouse strains
      and also reveal two previously unrecognized polymorphisms generated by SmaI and
      HinfI digestion. Evidence for differences in trans was found in a comparison of
      DNA binding nucleoproteins from kidney, but not liver, of B10.PL when compared
      with B10.M. These data, together with the high degree of sequence homology
      between human and mouse Bf 5' flanking regions, should prompt a search for
      polymorphic restriction sites and cis binding elements in the Bf promoter that
      could serve as markers of human MHC-associated renal pathology and variants in
      local MHC class III gene expression.

PMID- 1370686
TI  - Monocyte chemotactic and activating factor is a potent histamine-releasing factor
      for human basophils.
AB  - Recombinant monocyte chemotactic-activating factor (MCAF) has been shown to
      induce histamine release from human basophils with a dose response between 10(-9)
      and 10(-6) M. The peak of activity was reached at 10(-7) M. Histamine release by
      MCAF was rapid with an initial rate comparable with histamine release by an
      optimal dose of anti-IgE. MCAF led to peak histamine release within 1 min. 80% of
      the subjects tested were responsive to MCAF or anti-IgE, while all were
      responsive to FMLP. The percentage histamine release by MCAF was, however, less
      than that seen with anti-IgE or FMLP, but this was attributable to a lesser
      percent release in nonatopic subjects; atopic subjects responded similarly to all
      three agonists. MCAF was also shown to activate highly purified human basophils
      more readily than mixed leukocytes, and its activity was inhibited by a
      polyclonal rabbit antibody. At a suboptimal concentration (2.5 x 10(-9) M), MCAF
      was unable to prime the basophil to histamine release by other secretagogues.
      However, interleukin 3 (IL-3) and IL-5 could each prime basophils for MCAF
      induced secretion. Therefore, our results suggest that MCAF may be a major
      contributor to the histamine-releasing activity seen in peripheral blood
      mononuclear cell supernatants that has been designated histamine releasing
      factor(s).

PMID- 1370687
TI  - Identification of an autologous insulin B chain peptide as a target antigen for H
      2Kb-restricted cytotoxic T lymphocytes.
AB  - We have examined the CD8+ peripheral T cell repertoire of C57BL/6 (H-2b) mice for
      cytotoxic T lymphocyte (CTL) reactivities to insulin, using in vitro immunization
      with a chymotryptic digest of reduced bovine insulin. The results presented in
      this study demonstrate that potentially autoreactive H-2Kb-restricted cytotoxic T
      cells specific for an autologous insulin B chain peptide are present in the
      preimmune splenic T cell repertoire. The immunogenic peptide comprises residues 7
      15 from the insulin B chain and has features in common with naturally processed
      Kb-restricted peptides identified by others. The minimal peptide sequence
      recognized by these cytotoxic T cells is 10-15, which is highly conserved in
      mammalian species and constitutes a self-peptide in mice. The presence of class I
      major histocompatibility complex-restricted CTLs with potentially autoreactive
      specificities in preimmune animals raises the possibility of a role for such
      cells in autoimmune disease states. Possible mechanisms for the in vivo expansion
      of insulin peptide-specific CTLs are discussed.

PMID- 1370688
TI  - Crosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T
      cell adhesion.
AB  - Regulated adhesion enables T cells to migrate through tissue and transiently
      interact with an endless succession of cells. Monoclonal antibody (mAb)
      engagement of the CD3/T cell receptor (TCR) complex results in a rapid and
      transient augmentation of the adhesion function of LFA-1 and VLA integrin
      molecules on human T cells. We show in this study that mAb crosslinking of the T
      cell-specific accessory molecules CD7 and CD28, or treatment with the Ca2+
      ionophore A23187, results in the rapid induction of integrin-mediated adhesion to
      three distinct ligands: the extracellular matrix protein fibronectin, and the
      cell surface molecules ICAM-1 and VCAM-1. Like CD3 crosslinking, increased
      adhesion via CD7 and CD28 crosslinking appears to involve both protein kinase C
      (PKC) and cAMP-dependent protein kinases. In contrast, A23187 induction of
      adhesion is unaffected by PKC inhibitors. CD7 is preferentially expressed on
      naive T cells and is unique in being a potent inducer of naive T cell adhesion.
      Enhanced expression/function of adhesion-inducing molecules thus overcomes
      relative deficits in adhesion receptor expression.

PMID- 1370689
TI  - Structural and functional analysis of three D/L-like class I molecules from H-2v:
      indications of an ancestral family of D/L genes.
AB  - Three cDNA with D region gene features have been identified from the H-2v
      haplotype. Provisionally, the sequences have been designated as D/Lv1, D/Lv2, and
      D/Lv3. The coding segments for the antigen binding domain (ABD) of all three D/Lv
      genes were engineered into a class I genomic expression vector and expressed in L
      cells. FACS analysis of the three D/Lv-Ld gene transfectants revealed that the
      D/Lv1 molecules were recognized by both monoclonal antibodies (mAbs) 141 and 142,
      and the D/Lv2 molecules were recognized by mAb 143. In addition to the D/Lv1
      molecules, the mAb 141 also recognized the D/Lv3 molecules. Both the D/Lv1-Ld and
      D/Lv2-Ld transfectants were killed efficiently by H-2Dv region-specific
      alloreactive CTL. The D/Lv3 gene is the first identified D region gene other than
      D and L that is transcribed abundantly in spleen and the D/Lv3 RNA is present as
      two alternatively spliced forms. Structural analysis of the D/Lv3 hybrid
      molecules showed that it was susceptible to proteolysis and thermolabile at 37
      degrees C, suggesting D/Lv3 is a transcribed pseudogene. A parsimony tree
      analysis of three D/Lv sequences with a set of class I gene sequences revealed
      that the H-2v sequences clustered with D region genes. The presence of a third
      gene with D/L-like features in H-2v, yet structurally different from the known
      D/L alleles, raises the possibility that the current D/L genes evolved from a
      family of D/L-like genes, some of which are no longer represented among many of
      the mouse major histocompatibility complex haplotypes. The observation that D
      region alleles cluster into subgroups suggests that the alleles are not all
      related to each other by linear descent through a single locus. We propose that
      current alleles are derived from more than one ancestral locus in a manner
      similar to the origin of the gamma 2 a immunoglobulin constant region alleles.

PMID- 1370690
TI  - MACOP-B treatment in diffuse large-cell lymphoma: identification of prognostic
      groups in an Italian multicenter study.
AB  - PURPOSE: The prognosis of advanced-stage diffuse large-cell lymphoma (DLCL) has
      improved with the use of the third-generation regimens such as methotrexate with
      leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin
      (MACOP-B). However, different results have been reported. Therefore, we started a
      cooperative study to confirm the efficacy of MACOP-B. An analysis of prognostic
      factors was also performed to identify poor-prognosis patients. PATIENTS AND
      METHODS: Between June 1986 and March 1989, 180 patients with advanced-stage DLCL
      were treated with MACOP-B. MACOP-B was given according to the original scheme.
      Numerous clinical features possibly predictive for complete response (CR),
      disease-free survival (DFS), and survival were analyzed in univariate and
      multivariate analyses. RESULTS: One hundred twenty-seven patients (71%) achieved
      a complete remission, 20 (11%) achieved a partial remission, 24 (13%) had
      unchanged or progressive disease, and nine (5%) died due to toxicity. With a
      median follow-up of 28 months, 71% of 127 CRs remain in first remission.
      Predicted 3-year survival for all 180 patients is 60%, and 3-year DFS for the 127
      CRs is 67%. Overall toxicity was acceptable, with mucositis being the most
      frequent severe side effect. A multivariate regression analysis identified
      lactate dehydrogenase (LDH) level, bone marrow involvement, and tumor burden as
      independent risk factors for survival. These factors were also important for
      achievement of remission and DFS and allowed us to identify three distinct risk
      groups of patients with good, intermediate, and poor prognosis, with 3-year
      survival rates of 80%, 59%, and %29, respectively. CONCLUSIONS: These results
      confirm the effectiveness of MACOP-B in advanced-stage DLCL at low or
      intermediate risk; however, high-risk patients are in urgent need of new
      therapeutic approaches. A better definition of prognostic features would allow a
      more reliable comparison of different treatment regimens, as well as an effective
      tailoring of therapy by prognostic groups.

PMID- 1370691
TI  - Immunohistochemical, ultrastructural, and histogenetic considerations in a
      patient with melanotic neuroectodermal tumor of infancy.

PMID- 1370692
TI  - Identification of B-cell antigenic sites on HIV-2 gp125.
AB  - Synthetic peptides were used to identify continuous antigenic sites on the
      external envelope glycoprotein gp125 of human immunodeficiency virus (HIV)-2.
      Initially, seven HIV-2-positive human serum samples were screened with 172
      sequential nonapeptides containing a six-amino-acid overlap. This represents the
      entire gp125 molecule of HIV-2ISY. The antibody reactivity was found to be mainly
      restricted to 14 regions within gp125. Following these results, 33 longer
      peptides, 15-24 amino acids in length, were synthesized and tested against a
      larger number of samples. Eleven antigenic regions were thus identified. Two of
      these were detected within a region corresponding to the C1 region and four
      others within a region corresponding to the C2 region of HIV-1. The highest
      frequency of reactivity (90%) of 31 HIV-2 seropositive human serum samples was
      elicited by three peptides from a region corresponding to the V3 region of HIV-1.
      The C-terminal portion of this region was recognized by almost 80% of the
      samples. Reactive regions corresponding to the V4, V5, and N-terminal portion of
      V4 were also identified. A mouse monoclonal antibody reacting with gp125 was
      mapped to the N-terminal region of the molecule and was found to react with the
      sequence DVWNLFETS. The peptides were used to evaluate the antibody response of
      monkeys immunized with whole killed HIV-2 or simian immunodeficiency virus (SIV).
      The monkeys showed a pattern of reactivity similar to HIV-2-infected human serum
      samples. Postinfection samples from monkeys inoculated with HIV-2 or SIV reacted
      mainly to peptides from the V3 region. Two peptides were used to detect the
      seroconversion of two SIV-infected monkeys. Thus, we have demonstrated that human
      seroreactivity to HIV-2 gp125 occurs at a few distinct linear antigenic sites
      distributed at similar positions on the molecule as those in HIV-1 gp120.

PMID- 1370693
TI  - Heterocyclic excitatory amino acids. Synthesis and biological activity of novel
      analogues of AMPA.
AB  - The novel acidic amino acids 6a-c, 7, and 8 have been synthesized via 1,3-dipolar
      cycloadditions, using nitrile oxides and alkynes. The prepared compounds are
      heterocyclic analogues of glutamic acid with differing chain lengths. One of
      these compounds, (RS)-2-amino-3-(3-carboxy-5-methyl-4- isoxazolyl)propionic acid
      (ACPA, 8), was shown in [3H]AMPA binding studies to be more active than AMPA
      itself (IC50 = 20 nM compared to IC50 = 79 nM for AMPA). No affinity for NMDA
      receptors (NMDA-sensitive [3H]glutamic acid binding) was found, and only weak
      affinity in [3H]kainic acid binding (IC50 = 6.3 microM) was detected. The
      excitatory activity in rat cortical wedge also showed that ACPA was more potent
      than AMPA (EC50 = 1.0 microM compared to EC50 = 3.5 microM for AMPA). The
      depolarizing effect of ACPA could be fully antagonized by the selective non-NMDA
      antagonist 6-cyano-7-nitro-quinoxazoline-2,3-dione (CNQX), but was unaffected by
      the selective NMDA antagonist D-2-amino-5-phosphonovaleric acid (AP5).

PMID- 1370694
TI  - Crystal structure of nevirapine, a non-nucleoside inhibitor of HIV-1 reverse
      transcriptase, and computational alignment with a structurally diverse inhibitor.

PMID- 1370695
TI  - Synthesis and substance P receptor binding activity of androstano[3,2
      b]pyrimido[1,2-a]benzimidazoles.
AB  - Several heterosteroids containing a dihydroethisterone skeleton were prepared and
      shown to displace substance P in a receptor binding assay. Further biochemical
      (kinetic and Scatchard analyses) and pharmacological evaluation (substance P
      induced plasma extravasation and salivation in the rat) of a representative
      example in this series (5a) established that these compounds are competitive
      antagonists at the substance P receptor.

PMID- 1370696
TI  - Structure-activity relationships associated with 3,4,5-triphenyl-1H-pyrazole-1
      nonanoic acid, a nonprostanoid prostacyclin mimetic.
AB  - A series of phenylated pyrazoloalkanoic acid derivatives were synthesized and
      evaluated as inhibitors of ADP-induced human platelet aggregation. 3,4,5
      Triphenyl-1H-pyrazole-1-nonanoic acid (8d), with an IC50 of 0.4 microM, was the
      most potent inhibitor identified in this study. Biochemical studies determined
      that 8d increased intraplatelet cAMP accumulation and stimulated platelet
      membrane-bound adenylate cyclase in a concentration-dependent fashion.
      Displacement of [3H]iloprost by 8d from platelet membranes indicated that the
      platelet prostacyclin (PGI2) receptor is the locus of biological action.
      Structure-activity studies demonstrated that the minimum structural requirements
      for binding to the platelet PGI2 receptor and inhibition of ADP-induced platelet
      aggregation within this series are a vicinally diphenylated pyrazole substituted
      with an omega-alkanoic acid side chain eight or nine atoms long. Potency depended
      upon both side-chain length and its topological relationship with the two phenyl
      rings.

PMID- 1370697
TI  - The effects of 7.5% NaCl/6% dextran 70 on coagulation and platelet aggregation in
      humans.
AB  - The combination solution of 7.5% NaCl/6% dextran 70 (HSD) administered IV gives
      hemodynamic improvement in the treatment of hemorrhagic hypotension. Since
      earlier dextran solutions were reported to interfere with blood coagulation, the
      effects of HSD on the prothrombin time (PT), the activated partial thromboplastin
      time (APTT), platelet aggregation, and platelet concentration were studied. The
      HSD mixed with human plasma (1:5 and 1:10) slightly prolonged PT, but had no
      effect on the APTT, compared with saline controls. The HSD also decreased human
      platelet aggregation at the 1:5 dilution. In separate mixing studies, the
      hypertonic saline component of HSD was associated with the prolongation of PT and
      decreased platelet aggregation. The data from these studies indicate that at its
      proposed therapeutic dose, HSD is expected to have minimal effect on blood
      coagulation.

PMID- 1370698
TI  - Detection and staging of prostatic carcinoma after transurethral resection or
      open enucleation of the prostate: accuracy of magnetic resonance imaging.
AB  - A total of 17 patients who had undergone transurethral (16) or open (1)
      enucleation of the prostate for presumed benign prostatic hyperplasia had
      prostatic adenocarcinoma: 10 on the basis of examination of the resected specimen
      (stage A) and 7 upon rectal examination performed 2 to 120 months after
      prostatectomy for benign prostatic hyperplasia (stage B). In all patients
      magnetic resonance imaging (MRI) of the prostate was performed before radical
      retropubic prostatectomy. Preoperative imaging was compared to pathological
      findings with respect to the presence, location and stage of singular or multiple
      prostatic carcinomas. Carcinomas were categorized according to the location
      within the prostate: whether on the right or left side, and whether in the
      peripheral zone (anterior, anterolateral or posterior) or the transition zone.
      The sensitivity of tumor detection for cancers originating in the peripheral zone
      was 81%. However, the sensitivity of detection decreased to 0% for tumors
      confined to the transition zone. Tumor staging was not compromised by previous
      prostatic enucleation or transurethral resection. MRI correctly identifies
      carcinomas originating in the peripheral zone but cannot detect those confined to
      the transition zone.

PMID- 1370699
TI  - Re: Predicting radionuclide bone scan findings in patients with newly diagnosed,
      untreated prostate cancer: prostate specific antigen is superior to all other
      clinical parameters.

PMID- 1370700
TI  - Re: Treatment of benign prostatic hypertrophy by a long-acting gonadotropin
      releasing hormone analogue: 1-year experience.

PMID- 1370701
TI  - p53, c-erbB-2 and the epidermal growth factor receptor in the benign and
      malignant prostate.
AB  - Expression of the p53, the epidermal growth factor receptor (c-erbB-1) and c-erbB
      2 protein was studied in 34 men with benign prostatic hyperplasia and 29 men with
      locally advanced prostate cancer by means of an immuno-histochemical method.
      Strong staining for p53 was found in five of 29 prostate cancers (17%; mean 21%
      +/- 7% of malignant cells stained in the positive tumours), but no staining was
      found in benign prostatic hyperplasia (p less than 0.05). On the other hand, the
      epithelium in benign glands was stained positively for c-erbB-2 in 18% (6/34) and
      for the epidermal growth factor receptor in 88% (30/34); whereas malignant
      epithelium stained strongly for c-erbB-2 in 21% (6/29) and for the epidermal
      growth factor receptor in only 17% (5/29). Prostate cancer was associated with a
      significant decrease in epidermal growth factor receptor staining (p less than
      0.0001) and a significant increase in p53 staining (p less than 0.05). Most of
      the tumours were advanced and no significant relationship was observed between
      tumour stage and grade and expression of p53, the epidermal growth factor
      receptor or c-erbB-2. These findings demonstrate that altered expression of the
      epidermal growth factor receptor and p53 protein occurs in prostate cancer, but
      were not associated with other features of prognostic importance such as stage or
      grade.

PMID- 1370703
TI  - Effects of isoflurane on acetylcholine receptor channels. 1. Single-channel
      currents.
AB  - We studied the effects of the volatile general anesthetic isoflurane on single
      acetylcholine (ACh) receptor channels from clonal BC3H-1 cells. Excised patches
      were exposed to concentrations of isoflurane ranging from 0.18% to 4.0%, in the
      presence of 200 nM ACh. Isoflurane transformed channel behavior from isolated
      openings into bursts of brief openings. The channel open time decreased
      monotonically with the concentration of isoflurane; the mean open time was half
      of control at 0.4% isoflurane. The duration of bursts also decreased in the
      presence of isoflurane. The duration of brief closures within bursts was 300-400
      musec at concentrations above 0.3% isoflurane. The number of openings per burst
      increased moderately with isoflurane but did not exceed 3. The frequency of
      bursts increased with the concentration of isoflurane. The apparent single
      channel conductance decreased to 75% of control at 4% isoflurane. These results
      are discussed in terms of models of channel block. The concentration dependence
      of the open time, the gap duration, and the conductance are consistent with a
      sequential open-channel blocking mechanism in which most but not all blocking
      events were resolved. A model that assumes that isoflurane "blocks" both open and
      closed channels was then considered. This model is consistent not only with the
      open time data but also with the burst duration and number of openings per burst.
      These results indicate that isoflurane has effects on closed as well as open ACh
      receptor channels.

PMID- 1370702
TI  - Superoxide anion production by rat neutrophils at various stages of bleomycin
      induced lung injury.
AB  - This study investigated the level of activation of neutrophils isolated from rats
      at various stages of bleomycin-induced lung injury. Neutrophils were collected
      from blood and bronchoalveolar lavage (BAL) fluid and their superoxide anion (O2
      )-generating capacity measured in response to phorbol myristate acetate (PMA) and
      opsonized zymosan (OZ) stimulation. When stimulated with PMA, BAL neutrophils
      isolated from animals 3 days after bleomycin treatment had a significantly
      greater capacity to produce O2- than BAL neutrophils from animals 7 days after
      bleomycin treatment. The O2- levels of 7 day BAL neutrophils more closely
      resembled the resting levels obtained with circulating neutrophils from both
      control and bleomycin-treated animals. There were no differences observed in any
      of the neutrophils when stimulated with OZ. Myeloperoxidase levels were measured
      in plasma and BAL and found to be elevated only in plasma at 7 days after
      bleomycin. These data demonstrate that neutrophil activation does occur in this
      model and that the activation appears to be transient, in response to specific
      stimuli and compartmentalized between the lung and blood.

PMID- 1370704
TI  - High affinity [3H]dextrorphan binding in rat brain is localized to a
      noncompetitive antagonist site of the activated N-methyl-D-aspartate receptor
      cation channel.
AB  - [3H]Dextrorphan recognition sites were characterized in rat brain membranes. The
      pharmacological profile and regional distribution of [3H]dextrorphan binding
      sites appear to distinguish these sites from those labeled either by
      [3H]dextromethorphan or by putative sigma receptor radioligands. Data from
      thoroughly washed forebrain membranes suggest that [3H]dextrorphan predominantly
      labels a high affinity site defined by the activated state of the N-methyl-D
      aspartate (NMDA) receptor-channel complex. Regulation of [3H]dextrorphan binding
      by specific modulators of NMDA receptor function suggests that [3H]dextrorphan
      binding is predominantly localized to a domain of the receptor-channel complex
      also recognized by the prototypical noncompetitive antagonist radioligands (+)
      [3H]5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) and
      [3H]1-[1-(2-thienyl)cyclohexyl]piperidine (TCP). The critical relationship
      between [3H]dextrorphan binding and activation of the NMDA receptor-complex is
      suggested by the profound dependence of [3H]dextrorphan binding on glutamate in
      well washed membranes. Basal specific [3H]dextrorphan binding is nearly totally
      suppressed by the specific competitive NMDA antagonist D(-)-2-amino-5
      phosphonopentanoic acid (D-AP5), in a glutamate- but not glycine-surmountable
      manner. Glutamate and glycine each stimulate [3H]dextrorphan binding in a
      concentration-dependent manner, effecting maximal increases from control of up to
      30- and 14-fold, respectively. The NMDA receptor specificity of the modulation of
      [3H]dextrorphan binding by glutamate and glycine is indicated by the sensitivity
      of their effects to competitive antagonism by D-AP5 and 3-amino-1-hydroxy-2
      pyrrolidone (HA-966), respectively, and by the accordant rank orders of potency
      of glycine analogs as modulators of [3H]dextrorphan binding and as ligands at the
      strychnine-insensitive glycine site. The divalent cations Mg2+ and Zn2+ and the
      polyamines spermine and spermidine regulate [3H]dextrorphan binding in a manner
      consistent with radioligand interaction at the noncompetitive NMDA antagonist
      domain. Mg2+ and spermidine regulate [3H]dextrorphan binding biphasically in well
      washed forebrain membranes, whereas Zn2+ monotonically inhibits [3H]dextrorphan
      binding. Mg2+ and spermidine regulate [3H]dextrorphan binding with qualitative
      similarity and in a contrasting fashion to their regulation of [3H]MK-801 and
      [3H]TCP binding. First, spermidine and Mg2+ are significantly more potent
      modulators of [3H]dextrorphan binding than of [3H]MK-801 and [3H]TCP binding in
      well washed membranes; second, whereas the potencies of spermidine and Mg2+ as
      modulators of [3H]MK-801 and [3H]TCP binding are significantly increased by
      glutamate and glycine in well washed membranes, their potencies as regulators of
      [3H]dextrorphan binding appear to be unaffected by glutamate and
      glycine.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1370705
TI  - Radioiodinated substance P, neurokinin A, and eledoisin bind predominantly in NK1
      receptors in guinea pig lung.
AB  - In homogenates of guinea pig lung, binding of 125I-Bolton-Hunter-labeled
      substance P (BHSP), Bolton-Hunter-labeled eledoisin (BHELE), and
      [125I]iodohistidyl neurokinin A (INKA) was investigated. Equilibrium dissociation
      constants (derived from "cold" saturation experiments) for BHSP, INKA, and BHELE
      were 0.96 +/- 0.15, 1.61 +/- 0.26, and 1.98 +/- 0.12 nM, respectively. Specific
      binding of all three radioligands was increased 2-3-fold by 10 microM
      phosphoramidon. The rank order of potency of unlabeled tachykinins in competing
      against BHSP was substance P (SP) greater than [Sar9,Met(O2)11]-SP greater than
      SP methyl ester greater than neuropeptide gamma greater than neurokinin A greater
      than or equal to neurokinin B = kassinin greater than or equal to eledoisin
      greater than or equal to scyliorhinin II much greater than neuropeptide K,
      indicating binding to sites with the general characteristics of NK1 receptors.
      Similar rank potency orders were observed for INKA and BHELE, showing binding to
      NK1 sites, rather than to NK2 or NK3 sites, which are labeled with high affinity
      by these radioligands in other tissues. For all radioligands, competition curves
      for SP and the NK1-selective agonist [Sar9,Met(O2)11]-SP could be resolved into
      two components, representing high and low affinity binding sites. These were
      present in the approximate ratios 2:3 (for BHSP), 1:1 (for INKA), and 8:1 (for
      BHELE). Other agonist competition curves also yielded high and low affinity
      components. The data suggest that BHSP and INKA bind partly and BHELE
      predominantly to high affinity NK1 receptors. The nature of the low affinity
      site(s) could be another tachykinin receptor or a low affinity state of the NK1
      receptor. Binding to a "classical" NK2 receptor is unlikely, because selective
      NK2 receptor antagonists and analogs were very weak competitors. Our data suggest
      that, in addition to the NK1 receptor, another type of tachykinin receptor may
      exist in this tissue. The inability to detect NK2 binding sites is strikingly at
      variance with functional studies.

PMID- 1370706
TI  - Solubilization, purification, and functional reconstitution of 5
      hydroxytryptamine3 receptors from N1E-115 neuroblastoma cells.
AB  - 5-Hydroxytryptamine3 (5-HT3) receptors from N1E-115 neuroblastoma cells were
      solubilized using 1.1% n-octylglucoside; five other detergents were less
      effective. Purification was achieved by affinity chromatography using immobilized
      GR119566X and biospecific elution with quipazine. Saturation analyses with [3H]
      GR67330 binding revealed high affinity binding to homogeneous populations of
      sites in both the solubilized (Kd = 0.05 +/- 0.02 nM) and purified (Kd = 0.10 +/-
      0.04 nM) preparations. Competition experiments indicated that the solubilized and
      purified receptor preparations retained the characteristics observed in N1E-115
      cells in vivo. Polyacrylamide gel electrophoresis of the purified receptor
      revealed a single protein band of 54.7 +/- 1.3 kDa. The purified receptor was
      incorporated into liposomes, and the functional integrity of the protein was
      demonstrated by measurement of m-chlorophenylbiguanide-stimulated 22Na uptake.
      Saturation analysis of the reconstituted preparation revealed a Kd of 0.24 +/-
      0.07 nM and suggested that 0.2% of 5-HT3 receptors present in the original
      membrane preparation had been incorporated into liposomes.

PMID- 1370707
TI  - Allosteric inhibition of human immunodeficiency virus type 1 reverse
      transcriptase by tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and 
      thione compounds.
AB  - The reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is
      present in virions and infected cells as an heterodimer (p66/p51). A new class of
      potent and selective HIV-1 inhibitors, the tetrahydroimidazo[4,5,1
      jk][1,4]benzodiazepin-2(1H)-one and -thione (TIBO) derivatives, were found to
      exert their antiviral activity by interacting with monomeric HIV-1 RT (p66) in a
      way different from that of previously studied RT inhibitors such as
      azidothymidine 5'-triphosphate. Upon examination of the kinetic properties of the
      heterodimeric HIV-1 RT and its inhibition by TIBO compounds, a positive
      cooperativity between the subunits of the enzyme with regard to the 2'
      deoxynucleoside 5'-triphosphates and the template/primer was observed. The
      cooperativity with respect to the template/primer may result from a progressive
      dimerization in the presence of increasing concentrations of the template/primer,
      a process referred to as polysteric linkage. Because the cooperativity of p66/p51
      was abolished in the presence of TIBO, these compounds behave as allosteric
      inhibitors.

PMID- 1370708
TI  - Two monoclonal antibodies recognizing different epitopes on rat cytochrome IIB1
      react with human IIE1.
AB  - To identify human cytochromes P450 (P450) in the CYP2B subfamily, 14 human liver
      microsomal samples were screened by immunoblots developed with monoclonal
      antibodies that recognized seven distinct epitopes on rat IIB1. Two of these
      antibodies recognized a protein in all of the samples. This protein was termed
      P450BE. Using video-imaging densitometry, the levels of P450BE were determined
      and compared with levels of other P450s. An excellent correlation was seen (r =
      0.87) between P450BE and human IIE1. However, rat IIE1 did not react in
      immunoblot and enzyme-linked immunosorbant assays with the two anti-rat IIB1
      monoclonal antibodies. As previously observed, the levels of IIE1 in the samples
      correlated well (r = 0.88) with the ability of these human liver microsomes to N
      demethylate N-nitrosodimethylamine. The levels of P450BE also correlated well (r
      = 0.91) with the ability of the microsomes to N-demethylate N
      nitrosodimethylamine. In addition, excellent correlations were obtained when the
      levels of P450BE and IIE1 were compared with the ability of the microsomes to O
      deethylate ethoxycoumarin (r = 0.87 and r = 0.85, respectively). To identify the
      protein recognized by the anti-rat IIB1 antibodies, P450BE was purified from
      microsomes prepared from human liver D. Amino-terminal amino acid sequence
      analyses of P450BE revealed that the 18-amino acid sequence obtained matched the
      corresponding sequence of human IIE1. In addition, purified human IIE1 and P450BE
      migrated with the same apparent molecular weight in polyacrylamide gels.
      Furthermore, proteolytic maps of P450BE and IIE1, generated with two proteases,
      were found to be identical. Sequence alignments and antigenicity calculations
      identified three regions of rat IIB1 as likely candidates for the epitopes shared
      in common with human IIE1. In conclusion, this study indicates that caution must
      be taken when interpreting the results of immunochemical assays when species
      lines are crossed.

PMID- 1370709
TI  - The polyamine spermine has multiple actions on N-methyl-D-aspartate receptor
      single-channel currents in cultured cortical neurons.
AB  - Spermine potentiates the action of N-methyl-D-aspartate (NMDA) at micromolar
      concentrations but is less effective at millimolar concentrations. In cultured
      cortical neurons we demonstrate that spermine enhances NMDA receptor currents in
      a unique manner. At low concentrations (1-10 microM) spermine enhances NMDA
      receptor current by increasing channel opening frequency, and at higher
      concentrations (greater than 10 microM) it produces, in addition, a voltage
      dependent decrease in channel amplitude and average open time that limits its
      enhancing action. It is likely that these two actions of spermine, due to
      differences in concentration and voltage dependence, are mediated by independent
      sites on the NMDA receptor complex.

PMID- 1370710
TI  - Effects of steroids on gamma-aminobutyric acid receptors expressed in Xenopus
      oocytes by poly(A)+ RNA from mammalian brain and retina.
AB  - Electrical recordings were made in Xenopus oocytes to study the modulatory
      effects of steroids on gamma-aminobutyric acid (GABA) receptors expressed by RNA
      from mammalian brain and retina. GABA responses expressed by rat cerebral cortex
      poly(A)+ RNA were bicuculline-sensitive Cl- currents mediated by GABAA receptors.
      GABA responses expressed by bovine retina poly(A)+ RNA also were Cl- currents but
      were composed of two pharmacologically distinct components, one mediated by GABAA
      receptors and the other by GABA receptors with novel properties, which were
      resistant to bicuculline but were not activated by R(+)-baclofen, a selective
      agonist of GABAB receptors. As reported in neurons and in other expression
      systems, GABAA responses expressed in oocytes by cerebral cortex RNA were
      strongly and stereospecifically potentiated by 5 alpha-pregnan-3 alpha-ol-20-one
      (3 alpha-OH-DHP) and 5 alpha-pregnan-3 alpha,21-diol-20-one (THDOC). Threshold
      levels of potentiation were detectable using 1-2 nM steroid, and at
      concentrations of 50 and 500 nM 3 alpha-OH-DHP shifted the EC50 of cortex GABAA
      responses from a control value of 92 +/- 20 microM GABA to 40 +/- 4.3 microM and
      13 +/- 1.8 microM, respectively. However, even at concentrations as high as 50
      microM, 3 alpha-OH-DHP did not itself elicit appreciable membrane current
      responses through direct activation of the cortex GABAA receptors. In addition to
      potentiation, 3 alpha-OH-DHP and THDOC caused pronounced increases in the rate of
      desensitization of GABAA responses expressed by cortex RNA. Decay time courses of
      currents elicited by 1 mM GABA (90-95% of the maximum response) were fitted by
      the sum of two exponentials. Under control conditions, the time constant of the
      fast component was 4.4 +/- 0.6 sec and the slow component, 22.5 +/- 4.8 sec. 3
      alpha-OH-DHP at 500 nM and 5 microM reduced the time constant of the fast
      component by 52 +/- 7% and 84 +/- 5%, respectively, but showed little effect on
      the slow component. Unlike the potentiation effect, actions of pregnenolones on
      desensitization did not show stringent stereoselectivity, and 5 microM 5 beta
      pregnan-3 beta-ol-20-one (3 beta-OH-DHP) reduced the time constant of the fast
      component by 59 +/- 11%.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1370711
TI  - Point mutations in the abl SH2 domain coordinately impair phosphotyrosine binding
      in vitro and transforming activity in vivo.
AB  - We have constructed a series of point mutations in the highly conserved FLVRES
      motif of the src homology 2 (SH2) domain of the abl tyrosine kinase. Mutant SH2
      domains were expressed in bacteria, and their ability to bind to tyrosine
      phosphorylated proteins was examined in vitro. Three mutants were greatly reduced
      in their ability to bind both phosphotyrosine itself and tyrosine-phosphorylated
      cellular proteins. All of the mutants that retained activity bound to the same
      set of tyrosine-phosphorylated proteins as did the wild type, suggesting that
      binding specificity was unaffected. These results implicate the FLVRES motif in
      direct binding to phosphotyrosine. When the mutant SH2 domains were inserted into
      an activated abl kinase and expressed in murine fibroblasts, decreased in vitro
      phosphotyrosine binding correlated with decreased transforming ability. This
      finding implies that SH2-phosphotyrosine interactions are involved in
      transmission of positive growth signals by the nonreceptor tyrosine kinases, most
      likely via the assembly of multiprotein complexes with other tyrosine
      phosphorylated proteins.

PMID- 1370713
TI  - Modulating effect of tanshinones on mutagenic activity of Trp-P-1 and
      benzo[a]pyrene in Salmonella typhimurium.
AB  - The modulating effects of the Chinese medicinal plant 'Tan-shen', the radix of
      Salvia miltiorrhiza Bunge, on the mutagenic activities of Trp-P-1 (3-amino-1,4
      dimethyl-5H-pyrido[4,3-b]indole) and B(a)P (benzo[a]pyrene) were investigated
      using Salmonella typhimurium TA98. Ether- and hot water-extracted 'Tan-shen'
      enhanced both mutagens at low concentrations, but suppressed them at high
      concentrations. Extracts by ether treatment were more effective than those
      extracted by hot water. Dihydrotanshinone I, cryptotanshinone, tanshinone I, and
      tanshinone IIA were isolated from the ether extract by high performance liquid
      chromatography (HPLC) and were recognized to be the mutagenic modulators. 4
      tanshinones enhanced the mutagenicity of Trp-P-1 by 8-24-fold at 20
      micrograms/plate and the enhancement was reduced at the higher concentration.
      Dihydrotanshinone I suppressed Trp-P-1 activity completely at 100
      micrograms/plate.

PMID- 1370714
TI  - Chlorpromazine-induced damage on nucleic acids: a combined cytogenetic and
      biochemical study.
AB  - Chlorpromazine is now emerging as an adjuvant chemotherapeutic agent for the
      treatment of neoplasia. This was further supported in the present study by the
      following lines of evidence: it was shown that chlorpromazine causes damage in a
      series of native nucleic acids, though at somewhat high concentrations.
      Furthermore, chlorpromazine and caffeine were shown to act synergistically to
      potentiate the cytogenetic effect of adriamycin on human lymphocytes in vitro and
      on Ehrlich ascites tumour (EAT) cells in vivo. It is suggested that
      chlorpromazine alone or in combination with caffeine may exert its cytotoxic
      effect on normal and neoplastic cells not only indirectly, i.e. by facilitating
      the intracellular retention of adriamycin, but also directly by intercalating
      into nucleic acids.

PMID- 1370712
TI  - raf regulates the postnatal repression of the mouse alpha-fetoprotein gene at the
      posttranscriptional level.
AB  - The mouse alpha-fetoprotein (AFP) gene is transcribed at a high rate in liver
      during the second half of gestation. Its steady-state mRNA levels decrease 10(4)
      fold shortly after birth, at least in part as the consequence of a dramatic
      decrease in its transcription rate. The final basal level of AFP mRNA in adult
      liver is influenced by a trans-acting locus on chromosome 15 termed raf. Two
      strategies were used to demonstrate that the raf gene acts posttranscriptionally
      to affect the processing and/or stability of AFP transcripts. Transgenic mouse
      studies demonstrated that raf gene action is independent of both positive and
      negative transcription control elements of the AFP gene. Nuclear run-on analysis
      was used to confirm that transcriptions of both AFP transgenes and another
      endogenous raf-responsive gene, H19, are invariant with respect to the raf
      genotype. Thus, the postnatal repression of the AFP gene is mediated by both
      transcriptional and posttranscriptional mechanisms.

PMID- 1370715
TI  - Thioguanine-resistant mutant frequency in T-lymphocytes from a healthy human
      population.
AB  - Resistance to 6-thioguanine in T-lymphocytes was used to study in vivo somatic
      mutations in normal healthy adults. Donor age had a significant effect on mutant
      frequency at the hprt locus, showing an increase of 0.09/10(6) cells per year of
      age. No significant increase was associated with sex of donor, smoking habits,
      alcohol or coffee/tea intake, or X-ray exposure. The lower mutant frequency seen
      with contraceptive pill usage was probably due to the age difference between the
      groups of users and non-users.

PMID- 1370716
TI  - Frequency of mutant T lymphocytes defective in the expression of the T-cell
      antigen receptor gene among radiation-exposed people.
AB  - The frequency of mutant T lymphocytes defective in T-cell receptor gene (alpha or
      beta) expression was measured using the 2-color flow cytometric technique.
      Results for a total of 203 atomic bomb survivors, 78 of whom were proximally
      exposed (DS86 doses of greater than or equal to 1.5 Gy) and 125 of whom were
      distally exposed (DS86 dose of less than 0.005 Gy), showed that the mutant
      frequency was significantly higher in males than in females. No significant dose
      effects were observed. In contrast, a significant increase of mutant frequency
      was observed for 6 patients treated with Thorotrast, a contrast medium containing
      thorium-232 formerly used for radioligands. In addition, thyroid disease patients
      treated with 131I showed a dose-related increase of mutant frequency. It was
      suggested that the present T-cell receptor mutation assay has a unique
      characteristic as a biological dosimeter for measurement of recent exposures to
      genotoxic agents.

PMID- 1370717
TI  - Modulation of mutagenic properties in a series of DNA-directed alkylating agents
      by variation of chain length and alkylator reactivity.
AB  - Four series of aniline mustards linked to a DNA-affinic acridine chromophore by
      alkyl chains of varying length (2-5 carbon atoms) have been studied for their
      mutagenic properties, as estimated in four strains of Salmonella typhimurium and
      in Saccharomyces cerevisiae strain D5. The four series have very different
      mustard reactivities, as determined by the aniline link group (-O-, -CH2-, -S- or
      -SO2-). Some of the derived compounds cause frameshift mutagenesis which can be
      detected in TA98 and also "petite" mutagenesis activity, neither of which occur
      to significant extents with the parent mustards or with 9-aminoacridine. None of
      the derived compounds are as effective as the parent mustards in mitotic crossing
      over, nor do they show ability for frameshift mutagenesis in S. typhimurium
      TA1977 which is typical of acridines. Some of the compounds have comparable
      frameshift activity to compounds such as ICR-191, but appear to have a different
      base-pair preference. The results indicate clear structure-activity relationships
      for the spectrum of mutagenic activity, which relate to both chain length and
      alkylator reactivity, for these compounds.

PMID- 1370718
TI  - Selective gene mutation in MEL cells.
AB  - MEL cells, undergoing erythroid differentiation and parasynchronized by dimethyl
      sulfoxide (DMSO) induction, were irradiated with a 3-s pulse of UV light at
      sublethal dose. A large number of clones deficient in different gene functions
      are found in the progeny of the treated cells, if the pulse irradiation is
      performed 18-24 h from the start of DMSO induction. Kinetics of thymidine
      incorporation into DNA show that the period of sensitivity corresponds to the S
      phase. The results show that the activities of the tested genes are differently
      affected depending on the exact time of cell irradiation. Maximum percent
      inhibition of cells not expressing glucose-6-phosphate dehydrogenase (G-6-PD)
      (70%) is produced by irradiating at 20 h from the start of DMSO induction; 6
      phosphogluconate dehydrogenase (6-PGD) (55%), and hypoxanthine (guanine)
      phosphoribosyltransferase (HPRT) (33%), at 21 h; hemoglobin (50%), at 22 h. The
      time difference in the sensitivity to UV light is highly reproducible and has
      been exploited to isolate, with high efficiency, cellular clones deficient in any
      one of the tested functions. Determinations of enzymatic activities on cell
      lysates show that the expression of tested genes is actually altered in cells
      that, on the basis of cytochemical tests, appear unaffected by UV irradiation.
      While the production of mutant clones is observed only during the S phase of the
      cell cycle, immediate statistical damage of the cellular DNA is produced at all
      times of irradiation. This finding excludes that the two types of phenotypic
      alterations, blocked or altered gene expression, both propagated in the progeny
      of the cells as clonal properties, may derive from a preferential alteration of
      those functions during the S phase.

PMID- 1370719
TI  - Chromosomal aberrations and sister-chromatid exchanges induced by N-nitroso-2
      acetylaminofluorene and their modifications by arsenite and selenite in Chinese
      hamster ovary cells.
AB  - The frequencies of chromosomal aberrations (CA) and sister-chromatid exchanges
      (SCE) in Chinese hamster cells were significantly increased by the direct-acting
      mutagen N-nitroso-2-acetylaminofluorene (N-NO-AAF) at the concentration of 0.1
      mM. N-NO-AAF was prepared by nitrosation of the protohepatocarcinogen 2
      acetylaminofluorene. The induced CA, which included chromatid breaks, chromatid
      exchanges, chromosome breaks, and chromosome ring formation were significantly
      potentiated by the presence of sodium arsenite (10 microM), but not by
      hydroxyurea (20 mM) or cytosine arabinoside (25 microM). On the other hand, the
      clastogenic effect of N-NO-AAF was effectively inhibited by sodium selenite (100
      microM). Arsenite (10 microM) was shown to be moderately active in CA induction
      which was partially blocked by the presence of selenite (10 nM). N-Nitroso
      compounds such as N-nitroso-N-methylurea, N-nitroso-N-ethylurea and N-methyl-N'
      nitro-N-nitrosoguanidine were equally or more active in the induction of CA and
      SCE in CHO cells when compared with N-NO-AAF. The cell cycle was significantly
      delayed by the intervention of N-NO-AAF.

PMID- 1370720
TI  - Levels of direct-acting mutagens, total N-nitroso compounds in nitrosated
      fermented fish products, consumed in a high-risk area for gastric cancer in
      southern China.
AB  - A high gastric cancer mortality in Fujian province (Peoples Republic of China)
      has been associated with the consumption of certain salted fermented fish
      products such as fish sauce (FS). We have investigated the levels and nature of N
      nitroso compounds (NOC) and genotoxins present, before and after nitrosation, in
      49 FS samples collected from villages in this high-risk area, pooled into six
      samples. The concentrations of total NOC before nitrosation ranged from 0.2 to 16
      mumoles/l, and after nitrosation at pH 2 and pH 7, they rose by up to 4800- and
      100-fold, respectively. In nitrosated samples, 40-50% of total NOC was not
      extractable into organic solvents; volatile N nitrosamines accounted for 1-2% and
      N-nitrosamino acids for 8-16% of total NOC. None of the FS samples exhibited
      genotoxic activity, but after nitrosation all were weakly active in the SOS
      chromotest. The highest SOS-inducing potency was observed with nitrosated ethyl
      acetate extracts of most samples. The formation of methylating agents was
      measured by incubation of nitrosated FS with DNA and subsequent analysis of 7
      methylguanine adduct. 2 of the 6 nitrosated FS samples caused a slight increase
      in DNA methylation. 1 pooled home-made FS sample (the only one tested) contained
      tumour promoter-like substances, as measured by expression of certain EBV genes
      in Raji cells. HPLC fractionation of ethyl acetate extracts of FS samples allowed
      identification of three UV-absorbing peaks that, upon nitrosation, produced
      direct-acting genotoxins. This genotoxicity was partly ascribed to the formation
      of nitrite-derived arene diazonium cations that were characterized by a coupling
      reaction with N-ethyl-1-naphthylamine and thin-layer chromatography.

PMID- 1370721
TI  - Genotoxic effects and chemical compositions of four creosotes.
AB  - Four creosotes used in Finland for impregnating wood were tested in the Ames
      Salmonella test, the SCE test and the SOS chromotest. Compounds volatile at 37
      degrees C were assayed using the taped plate testing protocol. The creosotes were
      fractionated according to their natural boiling ranges and the fractions were
      tested in the Ames Salmonella assay. Chemical compositions of creosotes and
      fractions were determined by high resolution gas chromatography/mass
      spectrophotometry techniques and by reversed phase high performance liquid
      chromatography. Mutagenic activities were shown to reside in fractions having the
      highest boiling point ranges (greater than 290 degrees C). The concentrations of
      mutagenic polycyclic aromatic hydrocarbons in creosotes and in some of their
      corresponding distillation fractions, when compared with mutagenic activities,
      indicated synergistic or antagonistic interactions.

PMID- 1370722
TI  - The protective effect of beta-carotene on genotoxicity induced by
      cyclophosphamide.
AB  - The influence of beta-carotene on the clastogenicity of the indirect-acting
      mutagen cyclophosphamide (CPA) was investigated in mice, in vivo, for the
      induction of chromosome aberrations in bone marrow cells (BM). beta-Carotene
      (0.5, 1.0, 2.0, 5.0, 10, 25, 50, 100 and 200 mg/kg) was administered by gavage
      for 5 consecutive days. 4 h after the last treatment with beta-carotene, the mice
      were injected intraperitoneally with CPA, and the BM cells were fixed after 16,
      24 and 32 h for the evaluation of the frequency of chromosome aberrations. The
      results showed that beta-carotene was effective in reducing chromosomal damage
      induced by CPA with the increase of its concentration up to a level after which
      this effect was not observed. This anticlastogenicity was better detected when
      the cells were fixed at 32 h, although a tendency in reducing the CPA
      clastogenicity was already observed at 16 and 24 h. Our results suggest that beta
      carotene provides significant protection against the genotoxicity of CPA,
      although no dose-effect relationship on the frequencies of cells with chromosomal
      aberrations was observed.

PMID- 1370723
TI  - Oxygen radical-mediated mutagenic effect of asbestos on human lymphocytes:
      suppression by oxygen radical scavengers.
AB  - The mutagenic effect of chrysotile asbestos fibers and zeolite and latex
      particles on human lymphocytes in whole blood has been studied. It was concluded
      that their mutagenic activities were mediated by oxygen radicals because they
      were inhibited by antioxidant enzymes (SOD and catalase) and oxygen radical
      scavengers (rutin, ascorbic acid, and bemitil). It was proposed that oxygen
      radicals were released by phagocytes activated upon exposure to mineral dusts and
      fibers. The study of lucigenin- and luminol-amplified chemiluminescence of
      peritoneal macrophages stimulated by chrysotile fibers and zeolite and latex
      particles has shown that their mutagenic action is probably mediated by different
      oxygen species, namely, by the iron-oxygen complexes (perferryl ions) plus
      hydrogen peroxide, hydrogen peroxide, and superoxide ion, respectively. From the
      oxygen radical scavengers studied, rutin was the most effective inhibitor of the
      mutagenic effect of mineral fibers and dusts.

PMID- 1370724
TI  - Hypochlorous acid potentiates hydrogen peroxide-mediated DNA-strand breaks in
      human mononuclear leucocytes.
AB  - In this study the formation of DNA single-strand breaks in MNL in close proximity
      to activated phagocytes, or in contact with added H2O2 and/or HOCl, were
      evaluated. Neutrophils activated by phorbol myristate acetate (PMA), induced DNA
      strand breaks in neighboring lymphocytes which increased after 1-2 h incubation
      in a repair medium. These DNA-strand breaks could be prevented by the addition of
      catalase or substitution of the neutrophils with cells from a patient with
      chronic granulomatous disease. Inclusion of the myeloperoxidase (MPO) inhibitor,
      sodium azide (NaN3), to the system was associated with less damage after 1-2 h
      incubation and a faster repair rate. Exposure of MNL to added reagent H2O2 (12
      100 microM) was also accompanied by DNA damage. Addition of reagent HOCl (3-25
      microM) did not induce any DNA-strand breaks. However, when combined with H2O2
      (12.5 microM), HOCl increased H2O2-mediated DNA damage and compromised the repair
      process. Interactions between the phagocyte-derived reactive oxidants H2O2 and
      HOCl are probably involved in the etiology of inflammation-related cancer.

PMID- 1370726
TI  - Cytogenetic and survival adaptive responses in G1 phase human lymphocytes.
AB  - Human lymphocytes from six donors were treated with 5 cGy of X-rays followed by
      200 or 400 cGy in the first G1 phase after PHA stimulation, and assayed for
      cytogenetic aberrations and cell survival. Four donors showed cytogenetic
      adaptive responses with 400 cGy, and one with both 200 cGy and 400 cGy. Both
      exchanges and deletions were reduced, indicating that the cytogenetic adaptive
      response acts by restitution of chromosome breaks. Good correlations were found
      between nonaberrant cells and survival, although the former were often higher
      than the later, especially with the 400 cGy dose. In four of six donors, 5 cGy
      alone had significant effects on cell survival; however, this was independent of
      the 5 cGy effect on high-dose-induced responses. Two donors had survival adaptive
      responses with 5 + 200 cGy, while none were found with the 5 + 400 cGy treatment.
      The comparisons between the cytogenetic and survival responses suggests that a
      survival adaptive response will only be seen with a sufficient increase in
      nonaberrant cells. To date, adaptive responses to ionizing radiation have been
      reported to occur in G0, G1 and late S/early G2 human lymphocytes.

PMID- 1370725
TI  - Formation of genotoxic metabolites from anthraquinone glycosides, present in
      Rubia tinctorum L.
AB  - Rubia tinctorum L., a medicinal plant used for the treatment of kidney and
      bladder stones, contains a characteristic spectrum of 9,10-anthraquinone
      derivatives, which are substituted in only one of the aromatic benzo rings. The
      majority of the anthraquinones present in the plant itself or in plant extracts
      are glycosides. We investigated the metabolism of two such glycosides,
      alizarinprimeveroside (AlP) and lucidinprimeveroside (LuP). AlP given orally to
      rats was metabolized to alizarin (Al) and 1-hydroxyanthraquinone (1-HA). The
      reductive cleavage of AlP was also observed after treatment of this compound with
      rat liver enzymes (S9) and NADPH. 1-HA has been reported to induce unscheduled
      DNA synthesis (UDS) in primary rat hepatocytes (PRH) and intestinal and liver
      tumors in rats after chronic treatment. The in vitro genotoxicity of 1-HA was
      confirmed by our present investigations. We also observed that the glycoside AlP
      was active at inducing UDS in PRH, but the compound was inactive in the
      Salmonella/microsome assay. Oral administration of LuP to rats resulted in the
      excretion of lucidin and rubiadin. When LuP was treated with rat liver extract
      and NADPH, the compound was reduced to rubiadinprimeveroside (RuP), which was
      hydrolyzed to rubiadin. We have recently shown that lucidin is highly genotoxic
      in a battery of short-term tests. We now report that rubiadin is also highly
      genotoxic in Salmonella typhimurium. However, in contrast to lucidin, it requires
      metabolic activation. In the UDS assay in PRH, rubiadin was even more potent than
      lucidin and equal to the positive control DMBA. In addition, the glycoside LuP is
      active in the Salmonella/microsome assay as well as in the UDS assay. The present
      work demonstrates that the uptake of the anthraquinone glycosides AlP and LuP
      leads to the rodent carcinogen 1-HA, and to the highly genotoxic compounds
      lucidin and rubiadin. This extends our previous studies and supports our
      suggestion that the therapeutic use of Rubia tinctorum may involve a carcinogenic
      risk.

PMID- 1370728
TI  - Development of infants with iron deficiency.

PMID- 1370727
TI  - Restriction fragment pattern analysis of HPRT mutations induced in rat-liver
      epithelial cells by alkylating and arylating agents.
AB  - Structural alterations in the hypoxanthine-guanine phosphoribosyl transferase
      (HPRT) gene in genomic DNA of adult rat-liver (ARL) epithelial cells that were
      mutated by alkylating and arylating mutagens were studied by restriction enzyme
      fragment pattern (RFP) analysis. ARL cells were mutated with the direct-acting
      alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or the activation
      dependent arylating agents 7,12-dimethylbenz[a]anthracene (DMBA) and N-2
      acetylaminofluorene (AAF). Alterations in the HPRT gene of at least 10
      independent 6-thioguanine-resistant (TGr) clones mutated by each chemical were
      analyzed using 8 different restriction endonucleases; Hind III, EcoRI, BamHI,
      XbaI, Hae III, XhoI, MspI and PstI, and a full-length HPRT cDNA as a probe in
      molecular hybridization. Among the 10 MNNG-induced mutants, the RFPs obtained
      with most endonucleases displayed no changes, while an altered RFP was found in
      only one mutant using XbaI. None of the 10 DMBA-induced mutants displayed altered
      RFPs. Restriction analysis of the 10 AAF-induced mutants showed no abnormality in
      HPRT gene structure in most restriction digests, while altered RFPs were detected
      in one mutant using MspI and in two mutants with XbaI digestion. Overall, the
      studies reveal an absence of major DNA sequence changes in 26 of 30 induced
      mutants although the mutant phenotype of 4 of the TGr clones can be attributed to
      gross chromosomal changes or a point mutation at the restriction site. The
      absence of detectable alterations in the RFPs of the majority of the mutants is
      strongly suggestive of base substitution as the major molecular alteration
      underlying the mutant phenotype. The HPRT activity of 14 of 30 mutants was at
      least 5% of the wild-type level, which is consistent with a structural alteration
      in the gene product expressed as partial activity of the enzyme. Therefore, the
      data are interpreted as indicating that in the ARL cells, all 3 mutagens induced
      primarily localized alterations in base sequences in the HPRT gene together with
      a few mutations involving large sequence changes.

PMID- 1370729
TI  - [Cell biology from a medical viewpoint. X. Signal transduction].

PMID- 1370730
TI  - [Polymorph ventricular tachycardia with torsades de pointes caused by
      administration of terodiline (Mictrol)].
AB  - A 63-year-old female was admitted to the hospital because of collapse. She had no
      history of cardiovascular disease. Prior to admission she used co-trimoxazole,
      paracetamol, calcium tablets and 50 mg terodiline (Mictrol) daily because of
      bladder instability. Electrocardiography showed QT prolongation and polymorphous
      ventricular tachycardia with torsades de pointes. During admission she developed
      ventricular fibrillation, needing defibrillation. After withdrawal of terodiline
      and treatment with isoprenaline the symptoms and all ECG abnormalities
      disappeared. In this case terodiline was suspected of having been the causative
      agent. Terodiline shows structural resemblance to the anti-arrhythmic agent
      prenylamine, a known cause of torsades de pointes. Recently terodiline has been
      temporarily withdrawn from the worldwide market in order to investigate the
      causal relationship between this drug and cardiac arrhythmia and conduction
      disturbances.

PMID- 1370731
TI  - [Home care for patients with cancer].
AB  - A report of the Health Council of the Netherlands concerning home care for
      patients with cancer contains conditions required for the shift from hospital
      care to home care, but securing the maintainance of the quality of care. A new
      style of oncology outpatient clinic is proposed, which enables the general
      practitioner to provide for consultation tailored to the needs of these
      particular patients. This proposal has organizational and financial consequences.

PMID- 1370732
TI  - [Developments in the care for patients with cancer].

PMID- 1370733
TI  - [Activity of natural killer cells and granulocytes in peripheral blood and
      separated cells].
AB  - The natural killing of K 562 cells by whole blood from normal subjects was
      comparable with that shown by separated mononuclear cells. In order to establish
      the conditions for a reliable natural killer assay by using very small numbers of
      effector cells in whole blood, the isotope uptake of target cells was increased
      by a modified labelling method, which permitted the use of fewer target cells in
      the assay. The natural cytotoxicity of whole blood was augmented by interferon to
      the same extent as observed with separated mononuclear cells. The
      chemiluminescence of granulocytes in whole blood comparable with that of
      separated granulocytes. Taken together, these methods are considerably less
      tedious than the conventional methods, technique is also economical, and the
      results may reflect in vivo cytolytic processes much better.

PMID- 1370734
TI  - Transplantation in the nineties.

PMID- 1370735
TI  - Different aprotinin applications influencing hemostatic changes in orthotopic
      liver transplantation.
AB  - The effect of different aprotinin applications on hemostatic changes and blood
      product requirements in orthotopic liver transplantation was investigated in a
      prospective, open, and randomized study. From November 1989 to June 1990, 13
      patients received aprotinin as a bolus of 0.5 Mill. Kallikrein inactivator units
      (KIU) on three occasions in the course of an OLT, whereas 10 other patients were
      treated with continuous aprotinin infusion of 0.1-0.4 Mill. KIU/hr. Before and
      after reperfusion of the graft liver, signs of hyperfibrinolysis, measured by
      thrombelastography, were significantly lower in the infusion group. Tissue-type
      plasminogen activator (t-PA) activity increased during the anhepatic phase but to
      a significantly lesser extent in the infusion group. Blood product requirements
      during OLT were tendentiously higher in the bolus group but not significantly so.
      However, the use of packed red blood cells was significantly lower in the
      postoperative period, whereas there was no significant difference in fresh frozen
      plasma requirements between the two groups. All 23 patients have survived, and
      only one woman of each group required retransplantation due to severe host-versus
      graft reactions. Furthermore, we investigated the perfusate of the graft liver in
      both groups and detected signs of a decreased t-PA release in the infusion group.
      Our results demonstrate an advantage of aprotinin given as continuous infusion
      over bolus application in OLT.

PMID- 1370736
TI  - IgM and IgG alloantibody responses to MHC class I and II following rat renal
      allograft rejection. Effects of transplantectomy and posttransplantation blood
      transfusion.
AB  - Renal allograft rejection in rats and humans is a potent inducer of alloantibody
      to donor major histocompatibility complex antigens. Alloantibody in such
      presensitized recipients can cause hyperacute rejection of subsequent renal
      allografts. In order to characterize alloantibody production in rats
      presensitized by renal graft rejection, ACI (RT1a) kidneys were transplanted into
      untreated fully allogeneic PVG (RT1c) recipients and allowed to reject while one
      native kidney remained in situ for host survival. Serum samples collected at
      weekly intervals were analyzed by flow cytometry for IgM and IgG antibody binding
      to ACI lymphoid target cells. The specificity of alloantibody responses was
      assessed by (1) differential binding to congenic rat strain target cells
      expressing only donor class I (PVG.R1) versus both donor class I and II (PVG.1A)
      antigens, (2) differential binding to unseparated donor lymphoid target cells
      versus lymphoid target cells depleted of class II MHC antigen-expressing cells,
      and (3) specific blocking of monoclonal antibodies to donor class I (R2/10P,
      R2/15S) or class II (F17.23.2) epitopes. Alloantibody responses to both donor
      class I and II MHC antigens were detected. The initial IgM response to donor
      class I MHC antigens peaked at the time of rejection, followed by a steady
      decline to relatively low levels by 4 weeks posttransplantation. The IgM response
      to donor class II MHC antigens was found to be cyclical with apparent peaks at
      day 7 and 5-6 weeks. The IgG response to donor class I and class II MHC antigens
      reached maximum by 5-6 weeks before slowly decreasing. IgM and IgG alloantibody
      specific for class I and class II MHC antigens could be detected through 19 weeks
      posttransplantation. The effects on circulating alloantibody of two
      manipulations, posttransplantation donor specific blood transfusion and allograft
      removal, were examined in this model. The alloantibody responses to class I MHC
      antigens were not affected by giving DSBT weekly beginning at day 14 after
      transplantation. However, posttransplantation DSBT eliminated the second peak of
      IgM alloantibody to class II MHC antigens seen approximately 5-6 weeks
      posttransplantation and also decreased circulating IgG specific for class II
      antigens. Transplantectomy at day 5-7 days after transplantation had no apparent
      effect on circulating IgM or IgG alloantibody through 7 weeks
      posttransplantation. These data indicate that in a fully allogeneic rat renal
      allograft model alloantibody responses are elicited to both class I and II MHC
      donor antigens, but that the kinetics and regulation of the responses to class I
      differ from those to class II alloantigens.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1370737
TI  - IgG alloantibody responses to donor-specific blood transfusion in different rat
      strain combinations as a predictor of renal allograft survival.
AB  - Donor-specific blood transfusion prolongs the survival of fully allogeneic ACI
      (RT1a) renal allografts in PVG (RT1c) recipients from 7-10 days to greater than
      100 days. We have observed significant differences in the alloantibody (Ab1)
      responses to ACI renal allografts in control and DSBT-treated PVG recipients:
      DSBT is associated with decreased IgG and IgM alloantibody circulating in serum,
      deposited in the allograft, and produced in culture by splenocytes. In the
      present studies the effects of DSBT on alloantibody production and renal
      allograft survival were extended to examine other recipient strains: F344
      (RT1lv1), BN (RT1n), W/F (RT1u) and LEW (RT1l). Animals of each recipient strain
      were injected i.v. with 0.5 ml of ACI blood alone or followed by a renal
      allograft. Studies on the kinetics of IgM and IgG alloantibody responses were
      performed by flow cytometry on lymphocytes from donor ACI, PVG, and PVG.R1
      (RT1.Aa class I MHC antigen on PVG background) rats. In F344 and PVG rats, DSBT
      from ACI rats elicited a transient IgM response that peaked at day 7 and was not
      followed by a switch to IgG. In control PBS transfused F344 recipients, an ACI
      renal allograft stimulated both IgM and IgG alloantibody production. DSBT
      pretreatment significantly decreased circulating IgG alloantibody following ACI
      renal transplantation and prolonged graft survival in F344 recipients. In DSBT
      treated F344 recipients that rejected ACI renal allografts acutely, small amounts
      of IgG (5-12 mode channel shift) were detected in sera harvested 7 days after
      transplantation, whereas almost no IgG was detected in the sera from DSBT treated
      F344 rats that accepted their renal allografts indefinitely. In contrast, DSBT
      alone from ACI to BN, W/F, or LEW strains elicited a transient IgM response that
      peaked at day 7 and was followed by a strong IgG response that peaked on days 10
      14 and remained high through day 21. DSBT failed to prolong ACI renal allograft
      survival in any of these strains (survival less than 11 days in control and DSBT
      rats). The alloantibody response to DSBT in all five recipient strains examined
      was directed primarily to RT1.Aa class I MHC antigens, as determined by binding
      studies on lymphocytes from ACI, PVG and PVG.R1 rats and alloantibody blocking
      studies using biotinylated rat monoclonal antibodies to distinct epitopes of the
      RT1.Aa antigen. The relative magnitude of blocking of R2/10P and R2/15S binding
      by sera from BN, W/F, and LEW rats was: control allograft recipients greater than
      DSBT pretreated allograft recipients greater than DSBT alone.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1370738
TI  - Differential interactions among strains of tomato aspermy virus and satellite
      RNAs of cucumber mosaic virus.
AB  - Tomato and tobacco plants were inoculated with either of two strains of tomato
      aspermy virus, 1-TAV or V-TAV, and each of six isolates of cucumber mosaic virus
      satellite RNA (CMV-satRNA), B1, B2, B3, Ix, or WL2. Ribonuclease protection
      assays, used to detect total satRNA and encapsidated satRNA, revealed that G
      satRNA generated new satellite RNA not of the inoculated sequence. The other CMV
      satRNAs were compared for their ability (1) to replicate, (2) to modulate
      symptoms, (3) to reduce TAV accumulation, and (4) to alter the extent of
      encapsidation of TAV genomic RNAs. The fraction of B2- and B3-satRNAs
      encapsidated was greater for 1-TAV than for V-TAV, although spread and
      accumulation of the satRNA were similar for both helper viruses. These results
      suggest that CMV-satRNA may spread in a nonencapsidated form. Accumulation of CMV
      satRNA in systemically infected leaves was detected for all inoculum combinations
      except V-TAV and Ix-satRNA, for which the satellite RNA increased only in
      protoplasts and inoculated leaves of tobacco or tomato. In such inoculated
      leaves, Ix-satRNA was not detected in capsids. Thus the effectiveness of the TAV
      helpers of CMV-satRNAs may be controlled in at least some instances by the extent
      of satRNA spread or encapsidation rather than by the efficiency of satRNA
      replication. In contrast to infections initiated by inoculation of CMV and CMV
      satRNA, inoculation of 1-TAV or V-TAV and CMV-satRNA did not alter the relative
      amounts of viral genomic RNAs encapsidated or result in accumulation of large
      amounts of double-stranded satRNA.

PMID- 1370739
TI  - Cell-to-cell spread of HIV-1 occurs within minutes and may not involve the
      participation of virus particles.
AB  - Although virus infections have been classically studied with "cell-free" virion
      preparations, many animal viruses are able to spread both in vitro and in vivo by
      inducing cell-cell fusion. An efficient system to monitor the cell-to-cell spread
      of HIV-1 has been developed employing chronically infected H9 donor cells. Under
      appropriate conditions of cocultivation with uninfected cells, the synthesis of
      unintegrated viral DNA, monitored by Southern blot hybridization, occurred
      between 2 and 4 hr following infection; viral proteins were detected 8 to 12 hr
      following cocultivation and progeny virions were released into the medium by 16
      hr. The use of metabolic inhibitors or specific envelope/receptor antibodies
      revealed that the cell-to-cell spread of HIV required: (1) gp120-CD4 interaction
      and (2) reverse transcription. Light and electron microscopy, fluorescent dye
      redistribution, and soluble CD4 competition experiments all demonstrated that the
      HIV-induced cell-cell fusion began within 10 to 30 min of cocultivation.
      Surprisingly, the electron microscopic analyses also suggested that budding or
      mature virus particles did not participate in this process. Thus the virus
      induced cell-cell fusion observed is very likely the result of gp120/gp41
      proteins, on the surface of infected cells, interacting with CD4 molecules on
      uninfected cells. These findings are of immediate importance in understanding the
      mechanism(s) of HIV-1 transmission in vivo and for the design of effective
      vaccines and antiviral agents.

PMID- 1370740
TI  - Substance P in peritoneal fluid.
AB  - Substance P is a neuropeptide that has been identified in the ovary, fallopian
      tube, uterus, and vagina and in the hypothalamic-pituitary axis in both an animal
      model and human ovaries. We sought to determine if substance P is present in
      peritoneal fluid and, if so, whether it correlated with the cause of infertility.
      Its presence was determined by radioimmunoassay in the peritoneal fluid of 66
      patients undergoing diagnostic laparoscopy for clinical indications related to
      infertility. Total volume of peritoneal fluid and cycle day were recorded;
      patients were evaluated in groups according to diagnosis: endometriosis (n = 24),
      pelvic adhesions (n = 18), and normal controls (n = 24). The level of substance P
      (mean +/- SEM) was 122 +/- 19 pg/ml for endometriosis and 130 +/- 19 pg/ml for
      pelvic adhesions. These values were not significantly different from the normal
      controls (130 +/- 25 pg/ml). There was no significant difference in levels
      between follicular and luteal phase of the menstrual cycle. We conclude that
      substance P is present normally in peritoneal fluid and that its levels are not
      affected by pelvic endometriosis or adhesions.

PMID- 1370741
TI  - Partial hydatidiform moles have impaired differentiated function (human chorionic
      gonadotropin and human placental lactogen secretion) in response to epidermal
      growth factor and 8-bromo-cyclic adenosine monophosphate.
AB  - OBJECTIVE: The null hypothesis is that partial hydatidiform moles have normal
      differentiated function (human chorionic gonadotropin and human placental
      lactogen secretion) in response to epidermal growth factor and 8-bromo-cyclic
      adenosine monophosphate. STUDY DESIGN: Two complete moles, 10 partial
      hydatidiform moles, and 19 normal first-trimester placentas in monolayer culture
      were exposed to 10 ng/ml epidermal growth factor, 1 mmol/L 8-bromo-cyclic
      adenosine monophosphate plus 1 mmol/L theophylline, or control. Human chorionic
      gonadotropin and human placental lactogen secretion was measured. Frequency of
      response to stimuli was compared by chi 2 analysis, and hormone secretion was
      compared by analysis of variance. RESULTS: Partial moles demonstrated reduced
      frequencies of response of human chorionic gonadotropin and human placental
      lactogen to epidermal growth factor (partial moles 2/8 and 2/8, respectively;
      normal placentas 16/19 and 7/18, respectively; p less than 0.025) and of human
      chorionic gonadotropin to 8-bromo-cyclic adenosine monophosphate (partial moles
      3/5, normal placentas 13/16; p less than 0.005). CONCLUSION: Partial hydatidiform
      moles demonstrate impaired human chorionic gonadotropin and human placental
      lactogen secretory responsiveness to epidermal growth factor and cyclic
      nucleotides in comparison with normal first-trimester trophoblast.

PMID- 1370742
TI  - Catecholamines modulate epidermal growth factor-induced prostaglandin E2
      production in amnion-like (WISH) cells by means of a cyclic adenosine
      monophosphate-dependent pathway.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that
      catecholamines can modulate epidermal growth factor-induced prostaglandin E2
      production in amnion-derived cells via a cyclic adenosine monophosphate-dependent
      pathway. STUDY DESIGN: Human amnion-derived WISH cells were used as the model
      system to study the regulation of prostaglandin E2 production. The concentrations
      of prostaglandin E2 and cyclic adenosine monophosphate were measured by
      radioimmunoassay. Statistical significance was determined with the Student t
      test. RESULTS: Preexposure of WISH cells to either epinephrine, norepinephrine,
      or dopamine inhibited epidermal growth factor-induced prostaglandin E2
      production. In addition, propranolol blocked both the increase in cyclic
      adenosine monophosphate accumulation and the inhibition of prostaglandin E2
      production caused by epinephrine. CONCLUSIONS: These results indicate that
      epidermal growth factor-induced prostaglandin E2 production can be attenuated by
      preexposure of amnion cells to catecholamines and that the inhibitory effect of
      catecholamines on epidermal growth factor response may be mediated via a beta
      adrenergic receptor--coupled adenylate cyclase.

PMID- 1370743
TI  - Synthesis of cell-impermeable Cl-sensitive fluorescent indicators with improved
      sensitivity and optical properties.
AB  - Quinolinium compounds have been used as Cl-sensitive fluorescent indicators in
      cells and cell-free membrane fractions. To improve Cl sensitivity and for
      conjugation via nucleophilic reaction, the compounds 6-methoxy-N-(n
      aminoalkyl)quinolinium bromide hydrochloride (AAQ) with alkyl chain lengths (n)
      of 2 (AEQ), 3 (APQ), and 4 (ABQ) were synthesized. AAQ was water soluble,
      fluorescent, and quenched by Cl. The Stern-Volmer constants (KCl) for quenching
      of protonated AEQ, APQ and ABQ by Cl were 354, 322, and 272 M-1, respectively,
      higher than KCl for 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ; 118 M-1). To
      eliminate pH-dependent fluorescence, 6-methoxy-N-(3
      trimethylammoniumpropyl)quinolinium dibromide (TMAPQ) was synthesized (KCl, 310 M
      1). To red shift fluorescence excitation and emission spectra, 6-phenyl-N-(3
      trimethylammoniumpropyl)quinolinium dibromide (phenyl-TMAPQ) (emission 475 nm)
      and N-(3-trimethylammoniumpropyl)phenanthridinium dibromide (TMAPP) (excitation
      380 nm) were synthesized. AEQ and ABQ were conjugated with neutral dextran
      activated by cyanogen bromide to give indicator-to-dextran mole ratios of 5 to
      20. KCl values at pH 7.4 were 132 (AEQ-dextran) and 237 M-1 (ABQ-dextran). To
      construct a single molecule with Cl-sensitive and insensitive moieties, the
      bichromophores 6-methoxy-N-(n- dansylsulfonamidoalkyl)quinolinium with alkyl
      chains of two and four were synthesized. The new Cl-sensitive indicators were
      used for measurement of intracellular Cl activity and for the labeling of
      endocytic vesicles in 3T3 fibroblasts and T84 cells. Our results indicate that N
      substitution of quinoline with positively charged moieties gives increased Cl
      sensitivity, and extension of ring conjugation gives indicators with red-shifted
      fluorescence spectra.

PMID- 1370744
TI  - cAMP-activated chloride conductance in the colonic cell line, Caco-2.
AB  - In this study we investigated the properties of adenosine 3',5'-cyclic
      monophosphate (cAMP)-stimulated Cl- efflux in Caco-2 monolayers by measuring 125I
      efflux rates from preloaded cells and using patch-clamp electrophysiology. The
      addition of a cocktail containing 100 microM dibutyryl cAMP (DBcAMP), 10 microM
      forskolin, and 1 mM 3-isobutyl-1-methylxanthine caused a significant (P less than
      0.05) increase in the rate of 125I efflux. Dissipation of cell potential by
      adding valinomycin (4.5 microM) with 135 mM extracellular KCl reduced the cAMP
      evoked 125I efflux. These results suggest that cAMP-stimulated anion efflux
      occurs through a conductive pore or channel. Whole cell currents evoked with
      DBcAMP or forskolin were anion selective, PCl greater than PI greater than
      Pgluconate, and exhibited a linear current-voltage (I-V) relationship. Currents
      evoked with depolarizing or hyperpolarizing voltage steps showed no evidence of
      time-dependent activation or inactivation. Single Cl- channels were stimulated in
      cell-attached patches after treatment with cAMP. Onset of channel activity
      occurred after 20-30s of cAMP treatment, and the response was long lasting. The I
      V relationship for the channel activated in cell-attached patches by cAMP was
      best fit using two linear regressions. The slope conductance of the channel was
      3.2 +/- 0.6 and 7.4 +/- 0.3 pS at hyperpolarizing and depolarizing potentials,
      respectively. Substitution of 140 mM NaCl with 70 mM NaCl in the patch pipette
      resulted in a positive shift in reversal potential, indicating that the channel
      is anion selective.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370745
TI  - Regulation of annexin I in adipogenesis: cAMP-independent action of
      methylisobutylxanthine.
AB  - The differentiation of 3T3-L1 fibroblasts to adipocytes can be accelerated by the
      addition of 1-methyl-3-isobutylxanthine (MIX), insulin, and dexamethasone to the
      culture medium. During differentiation, we have demonstrated that the level of
      both annexin I mRNA and protein decreases. The half-times for this reduction were
      2 h and 10 h for annexin I mRNA and protein, respectively. Of the added agents in
      the differentiation medium, only MIX caused a decline in annexin I expression in
      3T3-L1 fibroblasts. The MIX effect in fibroblasts was reversible and required de
      novo transcription but not protein synthesis. Although MIX could be replaced by
      high levels of theophylline, neither agonists of the beta-adrenergic receptor nor
      intracellular second messengers, cAMP and cGMP, were able to reduce annexin I.
      The potential role of annexin I in cellular differentiation is discussed.

PMID- 1370746
TI  - Circulating galanin: origin, metabolism, and pharmacokinetics in anesthetized
      pigs.
AB  - The concentration of galanin-like immunoreactivity (GAL-LI) was 12.9 +/- 0.9
      pmol/l in porcine arterial plasma (n = 9) and ranged from 1 to 14 pmol/g in
      extracts of porcine gastrointestinal tract (n = 5), the colon being the richest
      gut segment. A significant (P less than 0.05) arteriovenous concentration
      difference of circulating endogenous GAL-LI occurred across the kidney (15.1 +/-
      2.3 vs. 6.2 +/- 0.5 pmol/l) and a hind leg (15.7 +/- 2.5 vs. 10.2 +/- 1.0
      pmol/l), whereas a negative gradient was observed across the intestine (12.5 +/-
      2.0 vs. 17.7 +/- 3.3 pmol/l) of anesthetized pigs. Passage through the brain,
      liver, or lungs did not change the concentration of endogenous GAL-LI
      significantly. During basal circumstances, the major source of circulating GAL-LI
      is therefore the gut. During infusion of 20 pmol.kg-1.min-1 of synthetic porcine
      galanin, a significant extraction occurred across the kidney (64.8 +/- 4.3%),
      hind leg (20.3 +/- 3.8%), and liver (19.7 +/- 4.3%). The overall metabolic
      clearance rate was 37.8 +/- 3.7 ml.min-1.kg-1. The half-life of galanin in plasma
      was 4.6 +/- 0.3 min, and the apparent distribution space was 255.6 +/- 31.4
      ml/kg. Incubation studies in vitro showed that the concentration of galanin,
      added to blood and plasma at 37 degrees C, was halved in 1 h, unless stabilized
      with EDTA and aprotinin.

PMID- 1370747
TI  - Pancreastatin inhibits pancreatic enzyme secretion by presynaptic modulation of
      acetylcholine release.
AB  - Pancreastatin (PST), a 49-amino acid polypeptide, inhibits endocrine and exocrine
      pancreatic functions. In this study, we examined the mechanism of the inhibitory
      action of PST on exocrine pancreatic secretion in the rat. In anesthetized rats
      prepared with pancreatic fistulas, intravenous administration of PST (500 pM.kg
      1.h-1) completely inhibited 2-deoxyglucose (75 mg/kg)-stimulated amylase output
      to below basal levels. Because 2-deoxyglucose acts to stimulate the vagus, we
      assessed the ability of PST to inhibit carbachol-stimulated amylase release from
      isolated rat pancreatic acini. PST suppressed neither carbachol- nor
      cholecystokinin-stimulated amylase release, indicating that PST inhibits exocrine
      secretion via indirect mechanisms. To examine neural pathways for inhibition, we
      used pancreatic lobules to examine the action of PST on intrapancreatic neurons.
      Incubation of pancreatic lobules in 75 mM potassium buffer stimulated amylase
      release by a cholinergic pathway. PST dose dependently inhibited potassium-evoked
      amylase release, with maximal inhibition of 49.6 +/- 11%. In addition, when
      lobules were incubated with [3H]choline, PST inhibited KCl-stimulated release of
      synthesized [3H]acetylcholine by 43 +/- 5.7%. Other studies demonstrate that PST
      inhibits rat pancreatic enzyme secretion via presynaptic modulation of
      acetylcholine release.

PMID- 1370748
TI  - Pharmacological characterization of histamine H3 receptors in isolated rabbit
      gastric glands.
AB  - The effects of the specific H3 agonist (R)-alpha-methylhistamine (alpha-MeHA) and
      the specific H3 antagonist thioperamide were examined on histamine release and
      acid secretion [( 14C]-aminopyrine (AP) accumulation) by isolated rabbit gastric
      glands. Thioperamide significantly enhanced basal histamine release from the
      glands (+50% at 30 min for 10(-7) M thioperamide; P less than 0.01), and this
      increase was prevented by alpha-MeHA. Histamine-elicited AP accumulation was
      increased by 18% (P less than 0.05) by 10(-7) M thioperamide and decreased by 70%
      (P less than 0.01) by 10(-6) M of the H2 antagonist ranitidine. Thioperamide
      alone significantly enhanced AP accumulation in a dose-dependent manner, whereas
      alpha-MeHA had no effect of its own on this accumulation. Thioperamide
      stimulation of basal AP accumulation was not modified by ranitidine but was 50%
      decreased by alpha-MeHA. Furthermore, carbachol-induced AP accumulation was
      decreased by alpha-MeHA and increased by thioperamide; the latter effect was not
      blocked by ranitidine. These findings support that H3 receptors pharmacologically
      distinct from H2 receptors are involved in the regulation of histamine-stimulated
      acid secretion. They further suggest that these gastric H3 receptors occur in the
      gastric glands as 1) H3 autoreceptors located on the histamine-secreting cells
      and acting to downregulate histamine release from these cells and 2) H3 (or H3
      like) receptors located on the parietal cell and regulating in a negative manner
      the acid secretory process.

PMID- 1370749
TI  - Distribution of smg p25A and smg p21s, ras p21-like guanine nucleotide-binding
      proteins, in the rat stomach.
AB  - Existence and distribution of small guanine nucleotide binding proteins (G
      proteins) such as smg p25A, smg p21s, and ras p21s were examined in the rat
      gastric mucosa. By immunoblot analysis using the specific monoclonal antibodies
      against smg p25A and ras p21 and the anti-smg p21 antiserum, smg p25A and smg
      p21s were detected in the gastric mucosa, while ras p21s were not detected. In
      immunocytochemical studies, moderate fluorescence of smg p25A was homogenously
      seen in the cytoplasmic portions of chief cells and surface epithelial cells. smg
      p21 immunoreactivity was detected in glandular cells and submucosal muscle layer
      in the mucosa. On the other hand, the cells constituting gastric glands were
      unstained with the anti-ras p21 monoclonal antibody, RASK-4. These results
      suggest that smg p25A and smg p21s exist as in other tissues and might exert
      their specific actions in the rat gastric mucosa.

PMID- 1370750
TI  - Neutrophil elastase stimulates tracheal submucosal gland secretion that is
      inhibited by ICI 200,355.
AB  - To investigate whether human neutrophil elastase (HNE) stimulates airway
      submucosal gland secretion, we studied the effect of purified HNE on secretion of
      35S-labeled macromolecules from isolated tracheal tissues from ferrets, dogs, and
      humans. HNE stimulated secretion in a concentration-dependent fashion, the
      secretory response being most pronounced in ferret tissues with a maximal
      response of 1,498 +/- 384% above baseline at 10(-5) M. In dog tissues, maximal
      secretory responses (509 +/- 169%) to HNE were much greater than to bethanechol
      (80 +/- 26%). Human tissues obtained several hours postmortem still responded to
      HNE (179 +/- 48% at 10(-5) M) significantly more than to the combination of
      isoproterenol, phenylephrine, and bethanechol (23 +/- 10%). Morphometric analysis
      of canine tracheal tissues showed degranulation of submucosal gland cells after
      HNE. A specific inhibitor of HNE (ICI 200,355) potently inhibited secretory
      responses in a concentration-dependent fashion. We suggest that HNE in airways of
      patients may cause hypersecretion and that treatment with ICI 200,355 may provide
      a strategy for therapeutic intervention.

PMID- 1370751
TI  - Contractile response of individual cardiac myocytes to norepinephrine declines
      with senescence.
AB  - The present study utilized individual isolated left ventricular cardiac myocytes
      from hearts of animals of a broad age range to evaluate the response to
      norepinephrine and to other stimuli that augment myocardial cell contractile
      performance. During electrical stimulation before drugs neither the amplitude nor
      the velocity of shortening normalized for resting cell length differed among
      cells isolated from 2-, 6- to 8-, or 24-mo-old animals. Norepinephrine augmented
      twitch amplitude and velocity about fourfold in cells from 2-mo-old hearts but
      only by 2.5-fold in cells from 24-mo-old hearts (age effect, P less than 0.001).
      In contrast, the contractile response to increases in bathing [Ca2+] or to the
      addition of the calcium channel agonist BAY K 8644 or of 8-(4-chlorophenylthio)
      adenosine 3',5'-cyclic monophosphate (CPT cAMP) did not vary with age. These
      results indicate that the age-associated contractile deficit during beta
      adrenergic stimulation is specific to the beta-adrenergic pathway and an age
      associated deficit in the net production of cAMP. This can be attributed to a
      diminished cardiac myocyte response to beta-adrenergic agonists, in contrast to
      modulation of the beta-adrenergic response by other receptor agonists, which are
      present in intact tissue but absent under the conditions of the present study.

PMID- 1370752
TI  - Ruthenium red selectively prevents Ins(1,4,5)P3-but not caffeine-gated calcium
      release in avian atrium.
AB  - We previously reported that inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and
      caffeine evoked contractures in saponin-permeabilized chick atria. The magnitude
      of contractures evoked by maximally effective concentrations of Ins(1,4,5)P3 were
      half those evoked by maximally effective concentrations of caffeine. In the
      present report, we tested the hypothesis that these two agents may act on
      distinct calcium-release mechanisms by comparing the effects of ryanodine,
      ruthenium red, and procaine on the responses to Ins(1,4,5)P3 and caffeine. We
      find that procaine inhibits both responses with similar mean inhibitory
      concentrations in the millimolar range. Nanomolar concentrations of ryanodine
      selectively potentiate the contractures induced by Ins(1,4,5)P3 but have no
      effect on those induced by caffeine. Micromolar concentrations of ryanodine
      inhibit responses to both Ins(1,4,5)P3 and caffeine in a use-dependent way.
      Ruthenium red prevents the response to Ins(1,4,5)P3 and potentiates that to
      caffeine, as if ruthenium red had enhanced calcium accumulation in the caffeine
      sensitive pool(s). Because we found that caffeine prevented the subsequent
      response to Ins(1,4,5)P3, but Ins(1,4,5)P3 had no detectable effect on the
      caffeine-induced contracture, we conclude that Ins(1,4,5)P3 and caffeine act on
      pharmacologically distinct calcium-release mechanisms that may reside in the same
      sarcoplasmic reticulum compartment.

PMID- 1370753
TI  - CD5 expression in B-cell small lymphocytic malignancies. Correlations with
      clinical presentation and sites of disease.
AB  - The authors examined the relationship between CD5 antigen expression and a nodal
      or extranodal presentation for three subtypes of low-grade non-Hodgkin's
      lymphoma: small lymphocytic (23 cases), small lymphocytic with plasmacytoid
      differentiation (10 cases), and lymphocytic lymphoma of intermediate
      differentiation (IDL) (29 cases). Antigen expression was studied by the avidin
      biotin complex immunoperoxidase technique in frozen sections and correlated with
      expression of other B- and T-cell markers. Lack of CD5 expression was
      significantly associated with extranodal presentation among the over-all study
      group (p less than 0.001), as well as for those with small lymphocytic lymphoma
      and IDL, but not for those presenting with small lymphocytic lymphomas with
      plasmacytoid differentiation (p less than 0.21). Eleven patients presented
      exclusively with extranodal disease involving lung and respiratory tract, skin
      and subcutaneous tissue, salivary gland, stomach, conjunctiva, and uterus. All
      such lesions were CD5 negative and had been classified as small lymphocytic (four
      cases), small lymphocytic-plasmacytoid (four cases), and IDL (three cases).
      Retrospective review of these 11 cases demonstrated common histologic features
      described as characteristic of lymphomas of mucosa-associated lymphoid tissue
      (MALT). Two additional patients presented with disseminated nodal disease and
      involvement of gastrointestinal tract and oropharynx; both were CD5 positive.
      These findings support the concept that at least two antigenically distinct B
      cell subpopulations may be involved in pathogenesis of low-grade small
      lymphocytic malignancies.

PMID- 1370755
TI  - 34 beta E12 monoclonal anticytokeratin antibody.

PMID- 1370754
TI  - Small intestinal stromal tumors with skeinoid fibers. Clinicopathological,
      immunohistochemical, and ultrastructural investigations.
AB  - Microscopic appearances of spindle cell tumors of the gastrointestinal tract are
      suggestive of smooth muscle origin; however, they usually lack specific muscle
      cell features by electron microscopy and immunohistochemistry, thus justifying
      their designation as stromal tumors. The present report describes nine cases of
      small intestinal stromal tumors with eosinophilic stromal globules composed of
      tangles of curved fibers with crossbands simulating an appearance of skeins,
      designated as skeinoid fibers. Patients' ages ranged from 28 to 87 years; and
      four were male. The tumors presented as well-delineated mural nodules ranging
      from 1.8 to 13 cm in size, causing intestinal obstruction or hemorrhage. Four
      were in the duodenum, three in the jejunum, and two unspecified. Microscopically,
      seven were benign; one, to the largest, was definitely malignant and metastasized
      to the liver. Another, the second largest (7.5 cm), showed moderate atypia with
      two mitoses per 10 high-power fields. The light microscopic appearance, including
      immunohistochemistry, were typical for small intestinal stromal tumors. Skeinoid
      fibers were strongly periodate-Schiff's procedure-positive and stained blue with
      the trichrome stain. They appeared as a few micra-sized specks to large globules
      reaching a few millimeters. Skeinoid fibers were also found in three neurogenic
      spindle cell tumors (an acoustic neuroma, a neurofibroma, and a plexosarcoma of
      the mesentery), suggesting that such fibers are possible ultrastructural markers
      for neurogenic tumors and thus small intestinal stromal tumors with skeinoid
      fibers are neurogenic in origin.

PMID- 1370756
TI  - Central neurocytomas. Critical evaluation of a small-cell neuronal tumor.
AB  - We report herein the clinical and pathological features of 20 patients with
      central neurocytomas. Investigations for various differentiation antigens and
      cell type-specific markers were performed by immunohistochemistry using paraffin
      embedded tissue. In addition, the expression of L1 adhesion molecule and of the
      various N.CAM (neural cell adhesion molecule) isoforms were investigated by
      immunoblotting studies in two frozen specimens. Central neurocytomas are
      clinically characterized by their intraventricular localization, occurrence in
      young adults, and good prognosis. It rarely occurs in patients over 50, but such
      cases have a poor prognosis. Total surgical excision is the best treatment.
      Radiotherapy is appropriate if surgery is incomplete or contraindicated.
      Histologically, central neurocytomas display the following features: an oligo
      like pattern, usually associated with large fibrillary rosettes or perivascular
      arrangement, and a rich endocrine-type vasculature. Central neurocytomas have a
      remarkably homogeneous antigenic profile. GFAP expression is only found in
      scattered reactive astrocytes, S100 protein in reactive astrocytes and rare tumor
      cells. Among the pan-neuroendocrine markers, central neurocytomas always express
      neuron-specific enolase; they frequently express synaptophysin but never
      chromogranin A. Synaptophysin is the most reliable immunohistological marker for
      central neurocytomas; however, immunoreactivity could be lost with long formalin
      fixation. In these cases, electron microscopy is used to support the neuronal
      nature of the tumor cells. The expression of L1 adhesion molecule and the isoform
      180 of N.CAM, indicates that central neurocytomas are formed by cells committed
      to neuronal phenotype. Nevertheless, advanced neuronal differentiation may be
      absent, as suggested by the persistence of embryonic N.CAM, the nonexpression of
      neurofilament proteins, and the absence of mature synapses in numerous cases.
      Central neurocytomas and neuroblastomas share some biochemical properties, but
      their respective clinicopathological features and biological behavior are
      dramatically different.

PMID- 1370757
TI  - Morphological diagnosis of parvovirus B19 infection. A cytopathic effect easily
      recognized in air-dried, formalin-fixed bone marrow smears stained with
      hematoxylin-eosin or Wright-Giemsa.
AB  - Readily identifiable intranuclear inclusions characterize parvovirus B19
      cytopathic effect in formalin-fixed, paraffin-embedded material. Such inclusions
      are not apparent in air-dried smears of bone marrow aspirates. Brief formalin
      fixation of bone marrow smears, followed by either hematoxylin-eosin or Wright
      Giemsa staining, permitted easy detection of parvovirus B19 inclusions in
      material from a renal transplant recipient with parvovirus B19 infection
      documented serologically and by electron microscopy. Formalin fixation of bone
      marrow and peripheral blood smears before hematoxylin-eosin or Wright-Giemsa
      staining may simplify the morphological diagnosis of parvovirus B19 infection.

PMID- 1370758
TI  - Alcohol stimulates the release of dopamine and serotonin in the nucleus
      accumbens.
AB  - The effects of acute IP administration (0.5, 1.0 or 2.0 g/kg) and local perfusion
      (25, 50 or 100 mM) of ethanol on the extracellular concentrations of dopamine
      (DA), serotonin (5-HT) and their metabolites in the nucleus accumbens (ACC) of
      the rat were studied with in vivo microdialysis coupled with a small-bore HPLC
      electrochemical detection procedure. The IP administration of 1.0 and 2.0 g/kg
      ethanol significantly (p less than 0.05) increased the extracellular levels of DA
      and 5-HT in the ACC whereas the 0.5 g/kg dose caused no change. In general, the
      extracellular levels of the 3 monoamine metabolites were not altered by IP
      ethanol except for a slight increase in the levels of homovanillic acid following
      the 2.0 g/kg dose. Local perfusion of 50 and 100 mM ethanol (but not 25 mM)
      through the microdialysis probe markedly increased (170-200% of control) the
      extracellular levels of DA in the ACC. Only the 100 mM concentration of ethanol
      altered the extracellular levels of 5-HT (2-fold increase), 3,4
      dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid. Addition of 100 microM
      ICS 205-930 (a 5-HT3 antagonist) to the perfusate markedly reduced the 100 mM
      ethanol-stimulated release of DA and 5-HT. Overall, the data suggest that ethanol
      can stimulate the release of both DA and 5-HT in the ACC and that the action of
      ethanol within the ACC may be mediated in part by 5-HT3 receptors.

PMID- 1370759
TI  - The changing role of surgery in metastatic non-seminomatous germ cell tumour.
AB  - In the last 2 years (1989-1990) we have treated a total of 53 patients with
      metastatic nonseminomatous germ cell tumours (teratoma). In ten cases surgery to
      remove residual abdominal masses was required on completion of chemotherapy and
      normalisation of tumour markers (HCG and AFP). In a further three patients with
      large intra-abdominal masses and little or no other sites of disease surgery was
      performed as a therapeutic intervention, in the context of plateauing or rising
      tumour markers despite intensive chemotherapy. In all three, this approach
      resulted in a rapid fall in tumour markers, and following further chemotherapy
      all three remain disease free at 7, 12 and 25 months. For this small sub-group of
      patient failing to respond to chemotherapy who have resectable lesions,
      interventional surgery should be considered as part of a combined approach to
      treatment.

PMID- 1370760
TI  - Differential expression of translation-associated genes in benign and malignant
      human breast tumours.
AB  - The human gene sequences encoding the translation-associated functions of alpha
      subunit of elongation factor 1 (EF-1 alpha) and the ubiquitin carboxyl extension
      protein (HUBCEP80) have been isolated by differential cDNA screening, and found
      to have significantly higher levels of expression in fibroadenomas (benign)
      compared with carcinomas (malignant) of the breast. These data parallel our
      previous findings that the acidic ribosomal phosphoprotein P2 also has higher
      expression levels in the benign breast tumours (Sharp et al., 1990). In situ
      hybridisation has shown these genes to be expressed predominantly in the
      epithelium of breast tumours.

PMID- 1370761
TI  - A study of silica nephrotoxicity in exposed silicotic and non-silicotic workers.
AB  - The possible human nephrotoxicity of silica has often been suggested by previous
      anecdotal reports and uncontrolled clinical studies of silicotic patients.
      Urinary excretions of albumin, alpha-1-microglobulin (AMG), and beta-N-acetyl
      glucosaminidase (NAG) were measured in 33 male workers exposed to silica (mean
      duration of employment 16 years) and 19 male age matched non-exposed subjects
      with no history of primary or secondary renal diseases. Significantly higher
      urinary excretions of albumin and AMG were found in the workers exposed to
      silica. Silicotic subjects (n = 7) also had significantly high excretions of
      albumin, AMG, and NAG. All but one of the silicotic patients had ceased exposure
      from three to 17 years before the study. Our findings suggest that prolonged
      exposure to silica is associated with chronic irreversible nephrotoxicity in
      exposed workers.

PMID- 1370762
TI  - [Initial experiences with a self-expanding metal stent in malignant ureteral
      compression].
AB  - Self-expanding metallic stents for the treatment of hydronephrosis were implanted
      in 12 ureters with malignant compression in 10 patients. In 3 ureters the stents
      were introduced percutaneously by a transrenal route; in 8 ureters introduction
      was transurethral and in one ureter by a combined route. Patency rate after 6
      months was 90.9%. In all cases the stent was able to withstand pressure by the
      tumour for the remainder of the patient's life. In one patient there was
      incrustation of both stents after 30 weeks, in another patient the ureter was
      kinked between the level of the stent and the distal ureter due to growth of the
      tumour. In all cases it was possible to overcome the obstruction during the
      lifetime of the patient by the use of a stent or by combining the stent with a
      plastic endoprosthesis.

PMID- 1370763
TI  - Effects of L-leucine methyl ester (Leu-OMe) on mouse peritoneal mast cells:
      characterization of histamine release versus cytotoxicity.
AB  - L-Leucine methyl ester (Leu-OMe), a lysosomotropic compound, has been found to
      eliminate several lysosome-rich cellular subtypes and all natural killer cell
      function from peripheral blood mononuclear cells. In this report, the effect of
      Leu-OMe on mouse peritoneal mast cells is described. The L-Leu-OMe induced the
      release of histamine from mouse peritoneal mast cells in a dose-dependent manner
      (0.25 to 3 mM), while its D-stereoisomer had no effect. L-Leu-OMe displayed also
      a potent histamine release effect on purified mast cells, indicating a direct
      effect on mast cells. The monitoring of radioactive chromium release versus
      histamine release showed that both processes may be unrelated for Leu-OMe
      concentrations inferior to 1.5 mM. At higher doses, L-Leu-OMe, but not its D
      stereoisomer, exerted a potent cytotoxic effect on mast cells. The secretory
      effect of Leu-OMe was temperature- and energy-dependent. Experiments performed in
      the absence of extracellular calcium and magnesium demonstrated that these
      divalent cations were not necessary for the Leu-OMe-induced histamine release,
      and their deprivation even involved a higher histamine release. The secretory
      characteristics of the Leu-OMe-induced histamine release appeared to be different
      from those of the IgE-induced ones. These results support the conclusion that
      exposure of mouse peritoneal mast cells to high doses of L-Leu-OMe results in
      killing of these cells, that are new targets of this lysosomotropic agent.

PMID- 1370764
TI  - Splenic and inguinal lymph node T cells of aged mice respond differently to
      polyclonal and antigen-specific stimuli.
AB  - Numerous changes have been reported to occur in T cell responsiveness of mice
      with increasing age. However, most of these studies have examined polyclonal
      stimulation of spleen cells from a limited number of mouse strains. This study
      investigated the influence of genetic background, source of lymphocytes, and type
      of stimulus on age-associated changes in T cells response. Con A-induced
      proliferation and IL-2 and IFN-gamma production by splenic lymphocytes (SL) was
      significantly greater in CBA/Ca mice compared to C57BL/6 mice, regardless of age.
      SL of both strains exhibited the predicted age-dependent decline in proliferative
      response and an increase in IFN-gamma production in response to Con A. In
      contrast, however, only SL from C57BL/6 mice demonstrated the predicted age
      dependent decline in Con A-induced IL-2 production; Con A-induced SL of young and
      aged CBA/Ca mice produced comparable amounts of IL-2. Differences in age
      associated responses to Con A were also observed between SL and inguinal lymph
      node (ILN) cells of CBA/Ca mice. In contrast to SL, ILN cells demonstrated an
      increased proliferative response to Con A. However, lymphokine production by Con
      A-stimulated ILN cells from aged CBA/Ca mice was similar to that of Con A
      stimulated SL from aged CBA/Ca mice. To determine if aged ILN T cells respond
      similarly to polyclonal and antigen-specific stimuli, keyhole limpet hemocyanin
      (KLH) responses of T cells isolated from ILN of aged and young CBA/Ca mice were
      examined. KLH-specific T cells from aged mice cultured with KLH-pulsed
      macrophages (M phi) from aged mice were significantly reduced in their ability to
      proliferate compared to KLH-specific T cells of young mice cultured with young
      KLH-pulsed M phi. In contrast to the expected results, the defect was not at the
      level of the T cells; proliferation of young T cells cultured with aged KLH
      pulsed M phi was equivalent to the proliferation of aged T cells cultured with
      aged M phi. These results suggest that aging has differential effects on
      polyclonal and antigen-specific T cell proliferation and on polyclonal
      stimulation of T cells isolated from different lymphoid organs and from different
      strains of mice.

PMID- 1370766
TI  - Effect of tolmetin sodium dihydrate on adhesion formation by intraperitoneal
      administration of antineoplastic agents.
AB  - Antineoplastic agents are currently being administered through catheters placed
      intraperitoneally to treat cancer localized to the peritoneum. This route allows
      for high local concentrations of antineoplastic drug at the tumor site with low
      levels of the drug systemically, thereby reducing the systemic toxicity. However,
      there are complications with this mode of delivery, including a decrease in
      catheter patency and induction of adhesion formation, which leads to decreased
      drug dispersion and limits continuing drug administration. A model was developed
      in rats to mimic this method of antineoplastic drug administration that produced
      fibrin deposition around the catheter and adhesion formation involving bowel,
      intestines and liver. All antineoplastic agents tested, including Adriamycin,
      methotrexate, bleomycin, mitoxantrone and cisplatin, induced moderate to severe
      adhesion formation with varying effects on catheter patency. When an
      intraperitoneal bolus of tometin encapsulated in liposomes was tested with
      Adriamycin delivered via an osmotic minipump, a reduction in adhesion formation
      was observed. However, highly significant adhesion reduction was found when
      tolmetin was coadministered with the antitumor agents.

PMID- 1370765
TI  - Reversal of multidrug resistance by an immunosuppressive agent FK-506.
AB  - FK-506, a novel immunosuppressive agent, was examined for its reversing effect on
      multidrug-resistant tumor cells. FK-506 at 3 microM completely reversed the
      resistance against vincristine (VCR) in vitro in VCR-resistant mouse leukemia
      P388 cells (P388/VCR). FK-506 also enhanced the cytotoxicity of VCR in
      Adriamycin(ADM)-resistant human ovarian cancer A2780 cells (AD10) and ADM
      resistant human myelogenous leukemia K562 cells (K562/ADM) in vitro. FK-506 was
      also effective in modulating sensitivity to ADM in AD10 cells in vitro. FK-506
      enhanced the chemotherapeutic effect of VCR in P388/VCR-bearing mice. When 20
      mg/kg FK-506 was combined with 200 micrograms/kg VCR, a T/C value of 151% was
      obtained. Under the protocol used in this study, FK-506 was more potent than
      cyclosporin A (CsA) and verapamil. FK-506 inhibited [3H]azidopine binding to P
      glycoprotein efficiently. The binding of VCR to K562/ADM plasma membrane was
      inhibited by FK-506 as effectively as by CsA. Moreover, the accumulation of VCR
      in AD10 cells was increased by FK-506 as efficiently as that of CsA and
      verapamil. These results indicate that FK-506 directly interacts with P
      glycoprotein like CsA and verapamil, inhibits the active efflux of vincristine
      from resistant cells, increases the vincristine accumulation in resistant cells,
      and thus overcomes multidrug resistance in vitro and in vivo.

PMID- 1370767
TI  - Correlation between repair patch ligation and nucleosome rearrangement in human
      cells treated with bleomycin, UV radiation or methyl methanesulfonate.
AB  - We have examined ligation and nucleosome rearrangement of repair patches in
      chromatin of human fibroblasts damaged with bleomycin (BLM), UV radiation and
      methyl methanesulfonate (MMS) to follow completion of excision repair involving
      different combinations of repair enzymes. Conditions were used that allowed
      analysis of the correlation between these two events over a large range (i.e.
      from 5% to greater than 99% ligated). Cells exposed to BLM were reversibly
      permeabilized with L-alpha-lysophosphatidylcholine and pulse-labeled with either
      [3H]dTTP or [3H]dThd to label selectively cells that 'reseal their membranes' at
      different rates. A striking difference is observed in the rates of ligation of
      these nascent repair patches, in that those labeled with [3H]dTTP are ligated
      much slower (25-50% unligated after 24 h) than those labeled with [3H]dThd (less
      than 5% unligated after 6 h). The nuclease sensitivity of [3H]dTTP-labeled
      patches also decreases more slowly, indicating that the rate of nucleosome
      rearrangement decreases compared to that of repair patches labeled with [3H]dThd.
      The rates of repair patch ligation and loss of nuclease sensitivity were also
      modulated in intact cells exposed to UV radiation or MMS by treatment with
      aphidicolin and/or hydroxyurea. A plot of relative nuclease sensitivity versus
      fraction of ligated repair patches yields an overall linear correlation of
      greater than 0.8 in each case, indicating that these two features of nascent
      repair patches are 'moderately coupled' events. These results support the idea
      that ligation of repair patches is a prerequisite for nucleosome rearrangement
      following three different modes of excision repair.

PMID- 1370768
TI  - Plasma levels of HGF in rats treated with tumor promoters.
AB  - Hepatocyte growth factor (HGF), mol. wt 105,000 is a potent mitogen for
      hepatocytes. HGF is strongly associated with compensatory regeneration in the
      liver after two-thirds partial hepatectomy and carbon tetrachloride
      administration. Plasma levels of HGF increase markedly during early stages of
      compensatory hyperplasia caused by these treatments. This is followed by an
      increase in HGF mRNA in the liver. This is in contrast to other growth factors
      for liver (epidermal growth factor, transforming growth factor alpha and acidic
      fibroblast growth factor) whose levels in plasma remain virtually undetectable
      during compensatory hyperplasia. We have shown that during augmentative
      hyperplasia caused by the tumor promoters alpha-hexachlorocyclohexane,
      phenobarbital and ciprofibrate, plasma levels of HGF also increase. This increase
      of HGF occurs during the transient wave of DNA synthesis caused by administration
      of these xenobiotics, providing further support for HGF as being the stimulator
      of DNA synthesis during both augmentative and compensatory hyperplasia.

PMID- 1370769
TI  - Methoxyamine modification of abasic sites protects CHO cells from the cytotoxic
      and mutagenic effects of oxygen alkylation.
AB  - The biological effects of the interaction of methoxyamine (MX) with
      apurinic/apyrimidinic (AP) sites produced in CHO cells by treatment with
      alkylating agents were examined. A decrease in cytotoxicity was observed after a
      10 min treatment with the SN1 alkylating agents ethylnitrosourea (ENU), N-ethyl
      N'-nitro-N-nitrosoguanidine (ENNG) and N-methyl-nitrosourea when MX was present
      in the culture medium. Furthermore MX reduced the number of mutations to 6
      thioguanine resistance induced by ENU and ENNG and the number of sister chromatid
      exchanges induced by ENU. In contrast, no protective effect of MX on survival was
      observed after a 10 min treatment with the SN2 alkylating agents diethylsulfate
      (DES), ethyl methane sulfonate and methyl methane sulfonate. A 3 h exposure to MX
      abolished the protective effect of MX on ENU-induced cytotoxicity and increased
      the cytotoxicity of DES. In vitro studies with synthetic oligonucleotides
      containing a single AP site opposite a normal guanine or O6-methylguanine showed
      that MX inhibits the cleavage of AP sites by the CHO AP endonuclease(s). A model
      is proposed in which different DNA lesions are involved in AP site formation
      after treatment with SN2 or SN2 alkylating agents. The involvement of specific
      alkylation products in cytotoxicity and mutagenesis is also discussed.

PMID- 1370770
TI  - Seven different assays of hyaluronan compared for clinical utility.
AB  - To compare six assays of hyaluronan (hyaluronic acid; HYA) in serum, developed in
      different laboratories, we analyzed 10 samples from each of three groups: healthy
      persons, patients with primary biliary cirrhosis, and patients with rheumatoid
      arthritis. All the assays are based on the use of affinity proteins specific for
      HYA, prepared from cartilage or brain tissue, and are analogous to RIA or enzyme
      immunoassay techniques. The assay results were of the same magnitude. Although
      statistical analysis indicated that the methods in some cases deviated
      significantly from one another, this variation was less than the physiological
      variation in the healthy population. Therefore, the results of clinical
      investigations in which the various methods have been used are comparable. The
      analyses have high specificity and sensitivity for primary biliary cirrhosis but
      are somewhat less suitable for detecting rheumatoid arthritis. A seventh
      laboratory, which obtained antibodies to HYA, used these in an RIA to analyze a
      separate series of serum specimens. Results were in agreement with those obtained
      by one of the other assays.

PMID- 1370771
TI  - Polypeptide nicks cause erroneous results in assays of human chorionic
      gonadotropin free beta-subunit.
AB  - Pregnancy and trophoblastic disease testing laboratories measure human chorionic
      gonadotropin (hCG; human choriogonadotropin) free beta-subunit to screen for Down
      syndrome and to diagnose persistent trophoblastic disease (invasive mole and
      choriocarcinoma). The results from various laboratories, however, vary widely for
      similar groups of patients. Average concentrations of free beta-subunit reported
      for persistent trophoblastic disease, for instance, range from 2.6% to 37% of
      total hCG. On hCG and its free beta-subunit, peptide bonds can be missing between
      beta-subunit residues 44 and 45 or between residues 47 and 48 (nicked molecules).
      To explore the possibility that the disparity in the reported concentrations of
      free beta-subunit was due to differences in recognition of nicked molecules by
      different antibodies, we generated 0% and 100% nicked beta-subunit standards and
      investigated their recognition in three separate immunoassays of free beta
      subunit. The immunoassay with antibody 1E5 did not recognize nicked beta-subunit
      (4% cross-reactivity with nicked beta-subunit) and thus detected only intact beta
      subunit. The immunoassay with antibody FBT11 gave similar results with nicked and
      nonnicked thus standards (96% cross-reactivity with nicked beta-subunit), as did
      the assay with antibody B204 (73% cross-reactivity with nicked beta-subunit).
      These two immunoassays thus measured total (nicked + nonnicked) beta-subunit. We
      used the three immunoassays to examine sera from normal pregnancy, Down syndrome
      pregnancy, hydatidiform mole, and persistent trophoblastic disease, all of which
      contain nicked and nonnicked beta-subunit molecules. The results obtained
      resembled the studies with nicked beta-subunit standards. The results from the
      FBT11 and B204 assays (total beta-subunit) were highest, results from the 1E5
      assay (intact molecules only) being as much as 10 times lower. We conclude that
      nicks in beta-subunit and the extent of recognition of nicked molecules by
      different antibodies affect the concentrations reported for free beta-subunit.

PMID- 1370772
TI  - An anti-peptide antibody that recognizes a neo-antigen in the CR1 stump remaining
      on erythrocytes after proteolysis.
AB  - Previous studies of erythrocyte CR1 levels in systemic lupus erythematosus (SLE)
      and other diseases with in vivo complement activation have led to the conclusion
      that CR1 levels fall because of loss of CR1 from erythrocytes by proteolysis-
      predominantly in the liver. In order to measure the existence of proteolysed CR1
      remnants on erythrocytes an antibody was raised to a peptide corresponding to the
      CR1 sequence between the proximal standard consensus repeat (SCR) and the
      transmembrane segment. This antipeptide antibody recognizes a neo-antigen found
      on trypsinized erythrocytes which has been demonstrated to represent the 'CR1
      stump'. The anti-'CR1-stump' antiserum detects proteolysed CR1 on the ex vivo
      erythrocytes of a patient with cold haemolytic antibody disease (CHAD). However,
      higher affinity antibodies will be needed to make anti-CR1-stump a satisfactory
      diagnostic reagent.

PMID- 1370773
TI  - Definition of an immunodominant T cell epitope contained in the envelope gp41
      sequence of HIV-1.
AB  - The majority of the immunodominant amino acid sequences of HIV-1 that have been
      characterized to date are coded for by hypervariable gene sequences. These
      variable sequences are however interspersed with sequences that are highly
      conserved between HIV strains. Immunogenic viral products with amino acid
      sequences that vary minimally between strains, and that consistently elicit both
      humoral and cellular immune responses, may be ideal for inclusion in a subunit
      vaccine. We studied HIV-seronegative and HIV-infected persons, classified as
      asymptomatic (AS), ARC or AIDS. Initially, we assessed the cellular immune status
      of each subject from results of T cell phenotype analyses, assays for serum
      levels of surrogate markers of disease progression, and responses to mitogens and
      recall antigen. In addition, we tested whether three short synthetic peptides
      derived from the conserved sequences of the envelope gp120 (aa 262-284) and gp41
      (aa 579-601), and core p17 (aa 106-125) regions of the HTLV-IIIB isolate, could
      elicit B cell as well as T cell responses in HIV-infected subjects. Only the gp41
      derived sequence was immunogenic at both B and T cell levels. To further
      characterize the gp41 epitope, we used a series of overlapping synthetic peptides
      derived from a conserved region of the envelope gp41 (aa 572-613). We thus
      identified an immunodominant 12-mer peptide sequence, gp41(8)(aa 593-604), which
      consistently elicited both T cell blastogenic and B cell (antibody) responses in
      AS HIV-seropositive individuals but not in ARC and AIDS patients. Linear
      regression analysis showed that in AS persons there was a strong positive
      correlation (P less than 0.0005) between the absolute CD8+ T cell numbers and the
      magnitude of blastogenic responses to the gp41(8)(aa 593-604). Furthermore, those
      AS subjects with T cells that proliferated in response to this gp41 analogue also
      had significantly greater serum levels of antibody to the same short peptide
      sequence than symptomatic ARC and AIDS patients. These results suggest that
      cellular responses to the immunodominant and highly conserved envelope sequences
      of HIV-1, associated with increased CD8+ T cells, may be important in the
      pathogenesis of HIV disease.

PMID- 1370774
TI  - Failure of Epstein-Barr virus-specific cytotoxic T lymphocytes to lyse B cells
      transformed with the B95-8 strain is mapped to an epitope that associates with
      the HLA-B8 antigen.
AB  - There are two types, A and B, of Epstein-Barr virus (EBV) and B95-8 represents
      the common type A laboratory strain. Herein, we show in a family study that
      paternal EBV-specific cytotoxic T lymphocytes (CTL) generated in short-term
      cultures following stimulation with the autologous B95-8-transformed
      lymphoblastoid cell line (LCL) or B cells freshly infected with the B95-8 isolate
      did not lyse haploidentical B95-8 LCL expressing the HLA-A1, -B8, -DR3 paternal
      haplotype. In contrast, the haploidentical B95-8 LCL expressing the HLA-A11, 
      B51, -DR7 paternal haplotype was strongly lysed. Moreover, paternal CTL generated
      in response to stimulation with the B95-8 LCL expressing the haploidentical HLA
      A1, -B8, -DR3 paternal haplotype included an allogeneic response against the
      maternal haplotype but no EBV-specific response as shown by the poor lysis of the
      autologous LCL target cells. However, stimulation with the haploidentical HLA
      A11, -B51, -DR7 paternal haplotype resulted in the generation of both an
      allogeneic and an EBV-specific response. CTL clones were generated from two HLA
      B8+ donors in response to stimulation with the autologous type A LCL transformed
      with wildtype EBV. The clones were cross-reactive for an immunodominant B95-8
      associated peptide epitope that interacted with the HLA-B8 allele but failed to
      lyse B95-8-transformed LCL targets unless the targets were pre-coated with the
      exogenous peptide. A CTL clone that was initially stimulated with the autologous
      BL74 LCL lysed the spontaneous autologous LCL and spontaneous LCL from an HLA-B8+
      donor, but failed to lyse the B95-8 LCL from that donor. The observed haplotype
      preference can be explained in terms of sequence variation between the B95-8 and
      the corresponding wildtype epitope. Our findings may help to clarify the role of
      EBV in the pathogenesis of primary Sjogren's syndrome which is closely associated
      with HLA-B8.

PMID- 1370775
TI  - Use of recombinant epitopes to study the heterogeneous nature of the
      autoantibodies against thyroid peroxidase in autoimmune thyroid disease.
AB  - Microsomal antigen is often recognized by the sera from patients with autoimmune
      thyroid disease (AITD). Human thyroid peroxidase (hTPO) is the main component of
      this antigen. In a previous study, we expressed hTPO cDNA as fusion proteins in
      prokaryotic vector; we thereby defined seven antigenic peptides by using two
      rabbit polyclonal anti-hTPO antibodies. In the present study we used the seven
      epitopes and three widened peptides to define the reactivity pattern of 61 sera
      from patients with AITD. Thirty-eight of them reacted against at least one of the
      seven hTPO-restricted epitopes; 14 were negative against the seven determinants
      but recognized one or two of the extended peptides. Thus, the antibody response
      against hTPO appeared to be highly heterogeneous in AITD patient sera. Moreover,
      we demonstrated that the immunodetection of the hTPO on Western blotting with
      deoxycholate solubilized microsomes can be perfectly correlated with the
      recognition of one of the epitopes in the region 554-735.

PMID- 1370777
TI  - Vascular invasion of colorectal carcinoma readily visible with certain stains.
AB  - We made use of hematoxylin and eosin (H&E) stain, Verhoeff van-Gieson stain for
      elastic tissue (EVG), and factor VIII-related antigen (FVIII-RA) to stain tissues
      excised from 94 patients with colorectal carcinoma. Of these 94, 49 died of
      disease within two years (Group I), and 45 survived for five years or longer
      (Group II) after surgery. In the tissues from both groups, the use of EVG stain
      revealed a higher incidence of vascular invasion than was seen with H&E stain. In
      Group I, the rates were 28.6 percent and 61.2 percent with H&E and EVG,
      respectively, and those in Group II were 4.4 percent and 31.1 percent,
      respectively. Conversely, the FVIII-RA stain showed a decrease in the incidence
      of vascular invasion in both groups. In Group I, when vascular invasion was
      examined in EVG-stained tissues, the incidence was 81.3 percent in cases of
      hematogenous metastases and 23.5 percent in those without hematogenous metastases
      (P less than 0.01). These differences were not evident with H&E. When observing
      the site of vascular invasion in tissues of the colorectal wall stained with EVG,
      intramural and extramural types of vascular invasion were seen in 20 percent and
      80 percent of cases in Group I and in 93 percent and 7 percent of those in Group
      II, respectively. Thus, not only the frequency, but also the site, of vascular
      invasion into the colorectal wall evidenced with EVG stain provides a more
      precise prediction of the recurrence of hematogenous metastases.

PMID- 1370776
TI  - Prevention of adjuvant arthritis in rats by a nonapeptide from the 65-kD
      mycobacterial heat shock protein: specificity and mechanism.
AB  - In a previous study we have shown that Lewis rats were completely protected from
      adjuvant arthritis by pretreatment with a nonapeptide (residues 180-188) of the
      65-kD mycobacterial heat shock protein. Here we address questions of specificity
      and mechanism(s) of protection. We demonstrate that complete protection against
      adjuvant arthritis can only be achieved by pre-immunization with the nonapeptide,
      while pretreatment with either the octapeptide (residues 181-188) of the 65-kD
      heat shock protein or unrelated immunogenic peptides failed to affect adjuvant
      arthritis. Interestingly, pretreatment with the nonapeptide of the 65-kD heat
      shock protein did not protect Lewis rats from type II collagen-induced arthritis.
      These results demonstrate that protection is both epitope and disease specific.
      Co-injection of the nonapeptide with mycobacterial antigen even at a weight ratio
      of 5:1 (nonapeptide:mycobacteria) failed to influence the disease, suggesting
      that the role of the nonapeptide is not as a 'blocking peptide'. T cells from
      rats immunized with nonapeptide respond to the nonapeptide as well as to
      mycobacteria in vitro, and adoptively transfer protection to naive recipients.
      The data indicate that the nonapeptide-induced protection may result from a T
      cell-mediated specific suppression.

PMID- 1370778
TI  - Sleep on a shortening day/night schedule.
AB  - In 2 experiments subjects were exposed for 3.5 weeks to a gradually (0.2 h/day
      initially) shortening day/night cycle, ending at 22.8 h and 22.0 h, respectively.
      Shortening of the cycle led to an initial but temporary increase of sleep
      latency. When the reduction ceased at 22.8 h and this length was maintained,
      sleep parameters were not further affected and the temperature rhythm in most
      subjects remained entrained to the 22.8 h period, although some instability
      occurred towards the end. In the 22.0 h experiment the continued reduction beyond
      22.8 h led to disturbed sleep on day 15, at a day length of 22.4 h. Total sleep
      time, stage 2 and sleep efficiency were then markedly reduced. At this point
      sleep coincided with the peak of the body temperature rhythm and the amplitude of
      the latter was extremely small. This was also the point when the body temperature
      rhythm 'broke out' from the sleep/wake rhythm and showed a large 6 h phase jump
      (delay). Towards the end of the experiment, when sleep was initiated in the
      circadian temperature trough, REM propensity was increased. It was concluded that
      several sleep parameters were affected by the reduction of the day/night cycle
      although the specific effects depended on the amount of phase advance and on
      whether desynchronization occurred. Within the range of entrainment, however,
      most sleep parameters were remarkably unperturbed by the considerable changes of
      circadian parameters.

PMID- 1370779
TI  - Frequency-domain localization of intracerebral dipolar sources.
AB  - A frequency-domain localization of intracerebral dipolar sources can be carried
      out basically in the same way as a time-domain localization, since the
      minimization problems to be solved in the two cases have exactly the same
      structure. The quantity to be minimized can be interpreted as a sum of residual
      variances of independent linear minimization problems. In the time domain there
      is one linear problem per sampling time, whereas in the frequency domain there
      are two linear problems per frequency. It is demonstrated that algorithms readily
      available for the solution of the time-domain inverse problem can also be used
      for the solution of the frequency-domain inverse problem. In this way it is not
      only possible to localize multiple dipoles, but also to combine information from
      different epochs and from different frequencies.

PMID- 1370780
TI  - Detailed evaluation of evoked potentials in Wilson's disease.
AB  - Detailed evoked potentials (EPs) were studied in 52 patients (28.7 +/- 11.9
      years) with Wilson's disease (WD). Various peak latencies, interpeak latencies
      and amplitudes of somatosensory, auditory brain-stem and visual EPs were
      significantly abnormal in the group of 28 neurologically symptomatic patients as
      compared to controls. Interhemisphere latency and amplitude differences tended to
      be increased without reaching significance, indicating a symmetrical rather than
      focal subclinical brain involvement. Selected conduction times of at least 1 EP
      modality were prolonged in all 4 patients with severe, in 16 of 18 with moderate,
      in 4 of 6 with mild, and in 4 of 24 patients without neurological symptoms.
      Auditory brain-stem and somatosensory EPs were more frequently prolonged than
      visual EPs (more abnormalities with check sizes of 13 than 54 min of arc).
      Cortical somatosensory EPs correlated well (P much less than 0.01) with either Fz
      or earlobe reference.

PMID- 1370781
TI  - Tactile interference differentiates sub-components of N20, P20 and P29 in the
      human cortical surface somatosensory evoked potential.
AB  - Somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded
      from up to 64 locations on the exposed cortical surface in 19 patients undergoing
      intracranial surgery for epilepsy and/or tumour removal. In view of previously
      described 'interference' effects on scalp SEPs, a continuous light tactile
      stimulus was applied to the palm and the first 3 digits of the stimulated hand in
      order to try to differentiate components due to input from cutaneous and other
      sensory receptors. The first cortically generated potentials, N20 at postcentral
      locations and P20 precentrally, could each be resolved into 2 subcomponents
      separated by about 2.5 msec. The later subcomponent was consistently the more
      attenuated by the interfering stimulus and is postulated to be due to input from
      rapidly adapting cutaneous mechanoreceptors. The earlier subcomponent could be
      due to input from muscle afferents or from slowly adapting cutaneous receptors
      which the interfering stimulus would have activated to a lesser degree. In 2
      cases the P29 potentials recorded from regions of the postcentral gyrus were
      dissociated. In one case the potentials recorded at adjacent electrodes were
      attenuated to differing degrees, and in the other the effect was maximal at
      different locations when the thumb, index and middle fingers were stimulated
      separately. The method therefore appears capable of distinguishing regions of the
      postcentral gyrus concerned with cutaneous input from different parts of the
      hand.

PMID- 1370783
TI  - Vector analysis of brain-stem auditory evoked potentials in patients with
      multiple sclerosis and subtentorial tumors.
AB  - Vector analysis of BAEPs was done in 10 patients with posterior fossa tumors and
      14 patients with MS. Latency abnormalities were found in both groups without
      significant differences. However, deviations of wave V vectors from its normal
      orientation were observed in tumor cases, correlated with tumor size and latency
      increase. It is concluded that vector deviations may indicate distortion of
      auditory pathways in the brain-stem.

PMID- 1370782
TI  - Morphological characteristics of the scalp far-field potentials evoked by median
      nerve stimulation in infants and children.
AB  - We investigated the somatosensory evoked potentials (SEPs) produced by median
      nerve stimulation in normal infants, children and adults, focussing upon the wave
      forms of the scalp far-field potentials (FFPs). In adolescents and adults, 3 or 4
      positive FFPs preceded the widespread N18 component on the scalp, corresponding
      to P9, P11, P13 and P14 (or P13-14). In infants and children, however, the scalp
      FFPs often included 5 positive waves, the initial three of which were
      characteristically sharp and brief. This distinctive wave form, with 5 positive
      FFPs, was correlated with an Erb's potential having a bipeaked negative phase. We
      studied the temporal relationship of the 5 positive FFPs to the Erb's potential
      and the cervical SEPs and concluded that the initial 3 brief positive waves were
      produced by overlapping of a bipeaked "P9" and bipeaked "P11." Both "P9" and
      "P11" are stationary waves that are thought to originate in the first-order
      afferents, so they probably reflect the bipeaked appearance of the compound nerve
      action potential.

PMID- 1370784
TI  - Auditory brain-stem response in zitter rats with genetic spongiform
      encephalopathy.
AB  - Zitter rats with genetic spongiform encephalopathy and hypomyelination developed
      an abnormal auditory brain-stem response (ABR) before the appearance of spongy
      lesions in the central nervous system (CNS). The ABR abnormalities were
      characterized by a dual peak of wave I, with a longer latency than in normal
      rats, and decreased or absent waves III and IV. Hypomyelination in both
      peripheral and central nerves may have been responsible for these abnormalities.
      The slow negative wave became wide and obscure with aging. These changes
      accompanied age-dependent progression of spongy changes in the CNS. These
      findings suggest that at least two mechanisms, one involving hypomyelination and
      the other causing spongy lesions, are responsible for the brain-stem auditory
      pathway dysfunction in zitter rats.

PMID- 1370785
TI  - Neuromagnetic mismatch fields to single and paired tones.
AB  - In 8 subjects we recorded multichannel magnetic responses to pitch changes in
      single 50 msec tones and in tone pairs (oddball paradigm; interstimulus interval
      745 msec). Either "A" (1 kHz) was standard (90%) and "B" (1.2 kHz) deviant (10%),
      or "AA" was standard and "AB" deviant in pairs with onset asynchrony of 75 msec.
      Subject did not pay attention to the tones. A mismatch field (MMF) was evident in
      responses to deviants with an equivalent source in the supratemporal auditory
      cortex, about 1 cm anterior to that for N100m. The MMF source was 3-fold stronger
      for tone pairs than for single tones.

PMID- 1370786
TI  - Very high-frequency rhythmic activity during SEEG suppression in frontal lobe
      epilepsy.
AB  - Intracerebral EEG (SEEG) recordings showing the development of fast rhythmic
      activity at seizure onset provide important evidence for the localisation of an
      epileptic focus. However, very high-frequency activity (greater than 50 Hz) of
      low amplitude relative to the background may not be apparent on the paper record
      due to the limited bandwidth and dynamic range of conventional SEEG recording and
      display methods. The use of a digital telemetry system with a fast sampling rate
      (400 Hz) and a wide dynamic range (1 microV resolution, 4 mV range) has allowed
      us to utilize expanded time scale SEEG plots and autoregressive spectral
      estimation to identify this activity in chronic SEEG studies. This may be
      particularly useful in frontal lobe epilepsy, where rapid propagation often
      prevents adequate localization using conventional methods of analysis.

PMID- 1370787
TI  - Computer-assisted placement of electrodes on the human head.
AB  - A system has been studied with 3 purposes: digitization of the head and
      mathematical representation of the scalp surface, assistance for electrode
      placement, and digitization of the exact 3-D position of each electrode after
      placement. The system has been validated in several ways, mainly by comparing the
      electrode locations obtained using the classical manual procedure based on the
      international 10-20 system of electrode placement, and through the assisted
      procedure based on the described system. The main result is improved
      reproducibility of the assisted procedure which is 3 times better than in the
      manual procedure.

PMID- 1370788
TI  - EEG spectra in dyslexic and normal readers during oral and silent reading.
AB  - EEGs of extensively screened dyslexics and normal readers were recorded while
      they read easy and difficult texts silently and orally, and during two other
      verbal tasks which also differed in overt speaking but had no reading component:
      narrative speaking and listening to a story. Mid-temporal, central and parietal
      leads were referenced to linked ears and to Cz. Large differences between tasks
      and between groups were found. With the linked ears reference, power was higher
      in all bands in oral reading than in silent reading, with the largest change
      occurring in the temporal leads. In the theta and low beta bands the difference
      between oral and silent reading was greater for controls than for dyslexics.
      These effects were not accounted for by differences in reading speed or in
      difficulty. Similar results were found in two cohorts of subjects. The difference
      between groups in theta was found only in the reading tasks. In contrast, the
      group difference in low beta was also found in the change from listening to
      speaking. This implies that the oral-silent group difference in theta is related
      to some aspect of the reading tasks other than the presence or absence of overt
      speaking, and that the low beta group difference is related to some aspect of
      overt speaking rather than to reading per se. With the Cz reference no group
      differences were found. It is suggested that the groups differ in the reading
      strategies they use, and the degree to which they shift strategy between the
      silent and oral tasks. We hypothesize that these cognitive differences are
      reflected in the theta activity from the temporal lobe. While there were many
      differences between the tasks in alpha power and asymmetry, no group differences
      involving alpha were found.

PMID- 1370789
TI  - 1,25-Dihydroxyvitamin D3 stimulates the secretion of insulin-like growth factor
      binding protein 3 (IGFBP-3) by cultured human osteosarcoma cells.
AB  - Several types of specific insulin-like growth factor binding proteins have been
      reported. These binding proteins are produced by peripheral tissue-derived cells
      and they modulate the functions of insulin-like growth factors. In this study, we
      investigated both the secretion of insulin-like growth factor binding protein 3
      (IGFBP-3) from a human osteosarcoma cell line MG63, and the effects of 1,25
      dihydroxyvitamin D3 (1,25-(OH)2D3) on the production of this binding protein. The
      beta subunit of IGFBP-3 was detected in perinuclear cytoplasm of MG63 cells by
      immunocytochemical study. Immunoblotting and SDS-PAGE analysis revealed that both
      150KD MW entire molecules and 40-60KD MW beta subunit molecules of IGFBP-3 were
      present in cell-conditioned media. 1,25-(OH)2D3 stimulated the production of the
      IGFBP-3 molecule by MG63 cells. The concentration of IGFBP-3 in conditioned media
      began to rise at 12 hours after the addition of 10(-8) M of 1,25-(OH)2D3 and
      reached peak level at 48 hours. Dose-dependent effects of 1,25-(OH)2D3 were
      demonstrated. The its maximum effect was observed at 10(-10) M. The concentration
      of IGFBP-3 in cytosol also increased at a 10(-10) M concentration of 1,25
      (OH)2D3. We conclude from these results that human osteosarcoma cells MG63
      produce the IGFBP-3 molecule and that 1,25-(OH)2D3 stimulates the production of
      this protein. These data suggests that the synergistic effects of 1,25-(OH)2D3 on
      the action of IGF-I on osteoblastic cells, which we reported previously, may be
      modulated by locally produced IGFBP-3.

PMID- 1370790
TI  - Dexamethasone treatment increases mitochondrial RNA synthesis in a rat hepatoma
      cell line.
AB  - Glucocorticoid hormones act in the nucleus of the cell to alter expression of
      specific genes and change cell metabolism. In liver, these hormones have been
      reported to increase mitochondrial respiratory activity, which is regulated by
      both nuclear and mitochondrial gene products. We examined the effects of the
      synthetic glucocorticoid, dexamethasone, on the expression of mitochondrially
      encoded genes in a rat hepatoma cell line, H-4-II-E cells. Dexamethasone
      treatment of these cells increased mitochondrial RNA (mtRNA) levels 3- to 4-fold
      without changing the amount of mitochondrial DNA mtRNA levels could increase by
      enhanced mitochondrial gene transcription, by decreased degradation, or by some
      combination of the two. To determine if messenger RNA (mRNA) stabilization
      contributed to the increase in mtRNA levels, we compared the decay rates of
      cytochrome b mRNA from dexamethasone-treated and control cells after inhibition
      of RNA synthesis; cytochrome b mRNA half-life was 80 min in both treatment
      conditions. The levels of incompletely processed RNA precursors for at least two
      mtRNAs increased 3-fold more and 24 h earlier than the mature mRNAs. These
      results suggested that dexamethasone treatment resulted in increased mtRNA
      transcription. In addition, we examined the incorporation of [3H]uridine into
      mtRNA. Dexamethasone treatment expanded the uridine triphosphate pools 1.6-fold
      in H-4-II-E cells and decreased uridine triphosphate specific activity 2.3-fold;
      correcting for this change in precursor pool specific activity demonstrated
      increased mtRNA synthesis in dexamethasone-treated cells. Changes in expression
      of nuclear-encoded proteins that regulate mitochondrial genome transcription are
      a possible mechanism by which dexamethasone can increase mtRNA levels in these
      cells.

PMID- 1370791
TI  - Gene expression and secretion of insulin-like growth factor-binding proteins
      during myoblast differentiation.
AB  - Numerous cell types have been reported to secrete insulin-like growth factor
      binding proteins (IGFBPs) in vitro. We have observed such IGFBPs in culture
      medium conditioned by the mouse myoblast cell line C2C12 and have identified
      IGFBP-2 among the secreted IGFBPs. Since C2C12 cells fuse in culture, these cells
      were used to examine IGFBP-2 mRNA expression and protein secretion during
      myogenic differentiation. Cells were harvested at approximately 80% of confluent
      density. Additional cultures were rinsed, fed differentiation medium, and
      harvested when approximately 15%, 60%, and 85% differentiated (fused). Northern
      and dot blot analyses were performed using total cellular RNA and a labeled cDNA
      specific for rat IGFBP-2. A single mRNA transcript of approximately 1.8 kilobases
      was observed. The level of expression of IGFBP-2 mRNA was highest in
      proliferating cells and decreased to 35%, 20%, and less than 10% of initial
      levels as differentiation progressed. Serum-free medium was conditioned for 24 h
      at each time point and collected from similar cultures. Three IGFBP species of
      32,000, 30,000, and 24,000 mol wt (Mr) were detected in conditioned medium by
      probing Western blots with [125I]IGF-I (ligand blot analysis). The intensity of
      the 32,000 Mr band decreased with differentiation. These same blots were probed
      with an antibody raised against the 34,000 Mr bovine IGFBP-2. This antibody
      specifically bound to only the 32,000 Mr IGFBP. The level of antibody binding
      decreased by 50%, 90%, and nearly 100% as differentiation progressed. It,
      therefore, appears that IGFBP-2 is expressed and secreted in a differentiation
      dependent manner by C2C12 myoblasts and may, thus, be involved in the process of
      myoblast differentiation.

PMID- 1370792
TI  - Cyclic changes in insulin-like growth factor-binding protein-4 messenger
      ribonucleic acid in the rat ovary.
AB  - We have previously shown that the mRNA for insulin-like growth factor-binding
      protein-4 (IGFBP-4) is present in adult rat ovaries, being localized
      predominantly to granulosa cells of atretic follicles. Now we have considered the
      following questions. What class of atretic follicles expresses IGFBP-4 mRNA? How
      does IGFBP-4 mRNA expression change during the estrous cycle? In keeping with our
      earlier work, a strong hybridization signal for IGFBP-4 mRNA was present in
      subpopulations of follicles throughout the estrous cycle. In all cases, the
      hybridization signal was localized to granulosa cells. Among the various types of
      follicles, IGFBP-4 mRNA was present almost exclusively in atretic graafian
      (antral) follicles. Morphologically, the outer layer of granulosa cells was
      positive, while cells in the cumulus oophorous were negative. By Northern
      analysis and in situ hybridization, the levels of IGFBP-4 mRNA were found to
      change over the estrous cycle. At 1000 h on proestrus (before the LH/FSH surge),
      the hybridization signal was relatively weak, being restricted in some (but not
      all) atretic Graafian follicles. At 2000 h on proestrus, (after the LH/FSH
      surge), essentially all atretic Graafian follicles were strongly positive for the
      message. The pattern of hybridization was similar at 0200 h on estrus, but the
      signal was less intense. At 1000 h on estrus, the hybridization signal was
      variable, ranging from very strong to weak or undetectable in atretic follicles.
      At this stage, however, the highest levels of IGFBP-4 mRNA were measured by
      Northern analysis; interestingly, a strong signal became apparent in the stromal
      cells. On diestrous day 1, the message levels decreased, and the signal was
      restricted to some atretic follicles. On diestrous day 2, the hybridization
      signal was very weak. There was virtually no detectable IGFBP-4 mRNA in any
      healthy follicle. In summary, we found that IGFBP-4 mRNA is 1) not detected in
      healthy dominant follicles; 2) localized almost exclusively to atretic Graafian
      follicles, except on estrus when it also appears in stromal cells; 3) localized
      predominantly to the mural granulosa cells in atretic follicles; and 4) undergoes
      changes during the cycle, being most prominent around estrous morning. The
      possibility that IGFBP-4 plays a role in the cyclic destruction of cohort
      Graafian follicles at estrus, perhaps by mechanisms involving hormones, is
      discussed.

PMID- 1370793
TI  - Maintenance of long-term secretory function by microencapsulated islets of
      Langerhans.
AB  - Continuous responses of insulin and glucagon to physiological challenges are
      essential for the maintenance of normoglycemia and for avoiding subsequent health
      complications. Transplantation of microencapsulated islets of Langerhans is a
      promising solution to obtain such a physiological system in diabetic patients.
      The integrity of the islets' secretory mechanism after encapsulation was studied
      using rat islets. Islets were isolated by collagenase digestion after which half
      of the islets were encapsulated with an alginate-poly-L-lysine-alginate membrane.
      The islets were then challenged for 24 h with glucose (0, 2.7, 5.5, or 20 mM)
      alone or with 0.1 mM 3-isobutyl-1-methyl-xanthine or 0.1 microM phorbol 12
      myristate 13-acetate (PMA), protein kinase A and C pathway stimulators,
      respectively. The bathing media and cellular contents were radioimmunoassayed for
      insulin and glucagon. Results obtained using a three-way analysis of variance for
      microencapsulated and free islets demonstrated that high glucose (P less than
      0.05), 3-isobutyl-1-methyl-xanthine (P less than 0.05), and PMA (P less than
      0.01) increased insulin secretion, and that glucagon secretion was decreased by
      high glucose (P less than 0.01) but increased by PMA (P less than 0.05). Free
      islets secreted more insulin than those which were microencapsulated under all
      conditions (P less than 0.01). This appeared to be due to the encapsulation
      process itself, however, as islets which had been 'freed' from the capsules also
      exhibited a reduced capacity for insulin secretion (P less than 0.05). Analysis
      of the hormone content of islets after microencapsulation demonstrated reduced
      insulin levels (P less than 0.01), thus, accounting for the reduction in insulin
      secretion. As the responses of microencapsulated islets to physiological
      regulation by glucose and protein kinases A and C were qualitatively identical to
      those of free islets, transplantation of microencapsulated islets into diabetic
      patients could mimic the physiological responses of the normal pancreas.

PMID- 1370794
TI  - Effects of testosterone on gonadotropin subunit messenger ribonucleic acids in
      the presence or absence of gonadotropin-releasing hormone.
AB  - There is accumulating evidence that the negative feedback actions of testosterone
      on the pituitary may contribute to the differential regulation of FSH and LH
      secretion in males. In the present study we measured steady state levels of the
      mRNAs encoding the gonadotropin subunits in pituitary cell cultures treated with
      10 nM testosterone (T) as well as in T-treated pituitary cells perifused with
      pulses of GnRH to explore further the direct actions of T on the pituitary. T
      treatment of pituitary cells in monolayer culture for 72 h increased FSH beta
      mRNA 1.5-fold (P less than 0.05), decreased alpha-subunit mRNA to 45% of the
      control level (P less than 0.05), and decreased LH beta mRNA to 75% of the
      control level (P less than 0.05). FSH and uncombined alpha-subunit secretion were
      increased and decreased by T, respectively, whereas basal LH secretion was
      unchanged. Treatment with 0.1 nM estradiol, a physiological concentration for
      males, did not change gonadotropin secretion or subunit mRNA concentrations.
      Between days 2 and 5 in culture in the absence of steroid treatment, steady state
      levels of LH beta and alpha-subunit mRNA declined (P less than 0.01) 52% and 61%,
      respectively, but FSH beta mRNA levels were unchanged. Pulsatile stimulation with
      2.5 nM GnRH every 1 h for 10 h increased FSH beta mRNA 2.8-fold (P less than
      0.05) and increased (P less than 0.05) alpha-subunit mRNA to 117% of the control
      level. When cell cultures were pretreated with T for 48 h and then perifused with
      pulses of GnRH, FSH beta, LH beta, and alpha-subunit mRNA levels were 66%, 74%,
      and 70% of the value during GnRH alone (P less than 0.05). T treatment also
      reduced (P less than 0.01) the amplitudes of FSH, LH, and alpha-subunit secretory
      pulses by 18%, 26%, and 41%, respectively. These data indicate that a portion of
      the negative feedback action of T is at the pituitary to regulate gonadotropin
      subunit gene expression. Our data reveal two opposing effects of T on FSH beta
      mRNA: a stimulatory action, which is GnRH independent, and an inhibitory effect,
      which is related to the actions of GnRH. These divergent actions of T represent
      one mechanism through which FSH and LH are differentially regulated.

PMID- 1370795
TI  - Androgens up-regulate the human prostate-specific antigen messenger ribonucleic
      acid (mRNA), but down-regulate the prostatic acid phosphatase mRNA in the LNCaP
      cell line.
AB  - To better understand androgen-regulated gene expression in the prostate, we have
      used Northern blot analysis to study the effects of androgens and other steroid
      hormones on the steady state levels of several human prostatic mRNAs in the LNCaP
      cell line. Dihydrotestosterone (40 nM) as well as a synthetic androgen, R1881
      (0.1 nM), increased the amounts of prostate-specific antigen (PSA) and human
      glandular kallikrein mRNAs; at the same time, the level of prostatic acid
      phosphatase (PAP) mRNA was down-regulated. Incubation of LNCaP cells with medium
      containing 0.1 or 1 microM R1881 for 3, 7, or 13 days resulted in up-regulation
      of PSA and human glandular kallikrein mRNAs and down-regulation of PAP mRNA.
      Thus, the two clinically important prostate-specific marker proteins are
      inversely regulated in this cell line. The level of human androgen receptor mRNA
      was also repressed by the androgen treatments. 17 beta-Estradiol and progesterone
      had effects similar to those of R1881 on gene expression in LNCaP cells. Our
      results show that the decrease in the amount of secreted PAP and the increase in
      the amount of secreted PSA caused by androgens and other steroid hormones in the
      LNCaP cells of epithelial origin are mediated by changes in the levels of the
      corresponding mRNAs.

PMID- 1370797
TI  - Developmental regulation of GLUT-1 (erythroid/Hep G2) and GLUT-4 (muscle/fat)
      glucose transporter expression in rat heart, skeletal muscle, and brown adipose
      tissue.
AB  - The expression of GLUT-1 (erythroid/Hep G2) and GLUT-4 (muscle/fat) glucose
      transporters was assessed during development in rat heart, skeletal muscle, and
      brown adipose tissue. GLUT-4 protein expression was detectable in fetal heart by
      day 21 of pregnancy; it increased progressively after birth, attaining levels
      close to those of adults at day 15 post natal. In contrast, GLUT-4 messenger RNA
      (mRNA) was already present in hearts from 17 day-old fetuses. GLUT-4 mRNA stayed
      low during early postnatal life in heart and brown adipose tissue and only
      increased after day 10 post natal. The expression pattern for GLUT-4 protein in
      skeletal muscle during development was comparable to that observed in heart. In
      contrast to heart and skeletal muscle, GLUT-4 protein in brown adipose tissue was
      detected in high levels (30% of adult) during late fetal life. During fetal life,
      GLUT-1 presented a very high expression level in brown adipose tissue, heart, and
      skeletal muscle. Soon after birth, GLUT-1 protein diminished progressively,
      attaining adult levels at day 10 in heart and skeletal muscle. GLUT-1 mRNA levels
      in heart followed a similar pattern to the GLUT-1 protein, being very high during
      fetal life and decreasing early in post natal life. GLUT-1 protein showed a
      complex pattern in brown adipose tissue: fetal levels were high, decreased after
      birth, and increased subsequently in post natal life, reaching a peak by day 9.
      Progesterone-induced postmaturity protected against the decrease in GLUT-1
      protein associated with post natal life in skeletal muscle and brown adipose
      tissue. However, GLUT-4 induction was not blocked by postmaturity in any of the
      tissues subjected to study. These results indicate that: 1) during fetal and
      early post natal life, GLUT-1 is a predominant glucose transporter isotype
      expressed in heart, skeletal muscle, and brown adipose tissue; 2) during early
      post natal life there is a generalized GLUT-1 repression; 3) during development,
      there is a close correlation between protein and mRNA levels for GLUT-1, and
      therefore regulation at a pretranslational level plays a major regulatory role;
      4) the onset of GLUT-4 protein induction occurs between days 20-21 of fetal life;
      based on data obtained in rat heart and brown adipose tissue, there is a
      dissociation during development between mRNA and protein levels for GLUT-4,
      suggesting modifications at translational or posttranslational steps; and 5)
      postmaturity blocks the decrease in GLUT-1 expression but not the induction of
      GLUT-4, observed soon after birth.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1370796
TI  - Transforming growth factor beta 1 inhibits gonadotropin action in cultured
      porcine Sertoli cells.
AB  - In the present study, we have tested the effects of transforming growth factor
      beta 1 (TGF beta 1) on FSH action toward aromatase activity and lactate
      production in cultured Sertoli cells isolated from immature porcine testes.
      Whereas treatment of Sertoli cells with FSH resulted in a dose-dependent increase
      (about 7-fold) in aromatase activity (conversion of testosterone into estradiol)
      (ED50 = 80 ng/ml FSH), the addition of TGF beta 1 reduced this gonadotropin
      action. The inhibitory effect of TGF beta 1 on FSH aromatase activity was dose
      dependent (ED50 = 0.1 ng/ml, 4 pM TGF beta 1) with a maximal decrease (about 40%)
      observed after a long term (48-h) treatment. TGF beta 1 exerted its inhibitory
      effect on FSH action at the level(s) of cAMP accumulation, exerting no apparent
      effect on the gonadotropin receptor or at a site(s) related to cAMP action. TGF
      beta 1 (2 ng/ml) significantly (P less than 0.002) reduced (52% decrease) FSH
      stimulated cAMP levels in cultured porcine Sertoli cells. However, such an
      inhibitory effect of the growth factor was no longer observed when stimulation of
      cAMP accumulation with FSH occurred in the presence of methyl isobutyl xanthine
      (0.5 mM), an inhibitor of cAMP-phosphodiesterase activity. This observation
      suggests that TGF beta 1 decreased cAMP levels by increasing catabolism of the
      cyclic nucleotide through an enhancement of cAMP-phosphodiesterase activity. The
      inhibitory effect of TGF beta 1 was not limited to the action of FSH on aromatase
      activity but also extended to the gonadotropin action (mediated by cAMP) on
      lactate production. As for the inhibitory effect of TGF beta 1 on FSH-induced
      aromatase activity, the inhibitory effect of the growth factor on FSH-stimulated
      lactate production was dose and time dependent with a maximal decrease (about
      30%) observed in the picomolar range (1 ng/ml, 40 pM) after 48 h treatment with
      TGF beta 1. In conclusion, the present study demonstrates that TGF beta 1
      attenuates FSH action on Sertoli cell activity and that such inhibitory action is
      potentially exerted through a decrease in cAMP levels. Because of the local
      production of TGF beta 1, it is suggested that the effects of the growth factor
      reported here might be exerted in the context of the testicular paracrine
      mechanisms.

PMID- 1370798
TI  - Forskolin and phorbol ester stimulation of neuropeptide Y (NPY) production and
      secretion by aggregating fetal brain cells in culture: evidence for regulation of
      NPY biosynthesis at transcriptional and posttranscriptional levels.
AB  - Using fetal brain cells in culture, we have previously shown that activation of
      the cAMP pathway by forskolin induces the production and secretion of
      neuropeptide Y (NPY). In this study we wished to ascertain 1) if activation of
      the protein kinase C pathway induces NPY production and/or secretion and if there
      is synergism between the pathways, and 2) the role of protein/RNA synthesis and
      influx of extracellular calcium. Aggregates, formed from dissociated cells
      obtained from the hypothalamus-olfactory tubercle area of 17-day-old rat fetuses,
      were cultured in serum-free medium for 12 days. The NPY content of aggregates
      incubated for 24 h with solvent (control) was 4.4 ng/flask, and the medium
      content was 7.6 ng. Forskolin (10 microM) or phorbol 12-myristate 13-acetate
      (PMA; 20 nM) marginally affected aggregate content, but each increased medium
      content 2- to 3-fold; forskolin and PMA were additive. When cycloheximide (75
      microM) was included along with forskolin, PMA, or forskolin plus PMA for a
      period of 10 h, the increase in NPY medium content was abolished. Actinomycin D
      (Act-D; 5 micrograms/ml) inhibited the response to each secretagogue in a time
      dependent manner. When Act-D was included along with forskolin, PMA, or forskolin
      plus PMA for a total period of 12 or 24 h, the 12 h increase in content was not
      affected, whereas the 24 h increase was abolished. When the presence of Act-D was
      limited to 0-24, 6-24, or 12-24 h, and forskolin plus PMA were included for the
      entire 24-h period, the increase in NPY content was inhibited by 94%, 57%, and
      12%, respectively. Verapamil (100 microM) totally inhibited the 24 h response to
      forskolin and partially (40-50%) inhibited the response to PMA or forskolin plus
      PMA. In none of these conditions was the inhibition of the increase in medium NPY
      content accompanied by an increase in aggregate content, nor was the NPY content
      of aggregate/medium of control cultures affected.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1370799
TI  - Insulin-like growth factors (IGFs) reduce IGF-binding protein-4 (IGFBP-4)
      concentration and stimulate IGFBP-3 independently of IGF receptors in human
      fibroblasts and epidermal cells.
AB  - Recent studies have provided a consensus that insulin-like growth factor-I (IGF
      I) stimulates IGF-binding protein-3 (IGFBP-3) in vivo and in vitro. While it also
      appears well established that IGFBP-1 is inversely related to insulin
      concentrations, evidence regarding regulation of other IGFBP is inconclusive.
      Using immunoprecipitation and Western ligand blot, we have characterized the
      IGFBPs released into conditioned medium (CM) by cells from the adult human
      fibroblast cell line N3652 and the human epidermal squamous cell carcinoma line
      SCL-1. N3652 cells expressed IGFBP-3, IGFBP-2, a 24-kilodalton (kDa) IGFBP
      presumed to be IGFBP-4, and IGFBPs at 30 and 28 kDa. SCL-1 expressed IGFBP-3 and
      a putative IGFBP-4, with intermediate bands at 34 and 30 kDa. As determined by
      ligand blot of CM from confluent cells 72 h after the addition of peptides to
      serum-free medium, IGF-I and IGF-II potently stimulated IGFBP-3 in both cell
      lines, but otherwise IGFBP regulation in the two cells diverged. In N3652 cells,
      IGFBP-3 concentrations in CM increased to 700% and 800% of basal levels in the
      presence of IGF-I and IGF-II (at 100 ng/ml; n = 5 experiments), respectively.
      IGFBP-3 was not affected by insulin up to 10 micrograms/ml. In contrast, IGFBP-4
      levels were diminished 54% and 73% by 100 ng/ml IGF-I and IGF-II, respectively,
      with no response to insulin. In SCL-1 cells, IGF-I and IGF-II were virtually
      identical in stimulating a mean 200% increase in IGFBP-3 (n = 5 experiments).
      Insulin was less potent, but caused a significant stimulation of IGFBP-3 levels.
      IGF-I, IGF-II, and insulin all stimulated an approximately 50% increase in IGFBP
      4 concentrations. To test the hypothesis that IGF-induced alterations in IGFBP-3
      and IGFBP-4 concentrations were regulated via the type 1 IGF receptor, we
      attempted to block IGFBP changes with type 1 IGF receptor antibody alpha IR-3 and
      to induce IGFBP changes with an IGF-II analog, [Leu27]IGF-II, with little
      affinity for the type 1 receptor. alpha IR-3 failed to block either the IGF
      induced rise in IGFBP-3 in each cell line or the decline in IGFBP-4 in N3652 CM.
      [Leu27]IGF-II was as potent as IGF-II or IGF-I in inducing changes in IGFBP-3 and
      IGFBP-4 concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1370800
TI  - Clinical relevance of a dipole field in rolandic spikes.
AB  - The clinical presentation of 366 children with rolandic spikes was examined to
      determine whether the presence of a temporal-frontal dipole field is associated
      with a lower incidence of clinical abnormality. Comparisons were made between the
      clinical presentation of 99 children with temporal-frontal dipole discharges
      versus 267 children with nondipole rolandic discharges. Criteria examined were
      birth history, developmental milestones, school history, total number of
      seizures, neurological examination, and computed tomography (CT) findings. For
      all clinical parameters, except birth history and CT finding, there was a lower
      incidence of clinical abnormality in the group with dipole discharges (p less
      than 0.001). The clinical profile seen with temporal-frontal dipole discharges
      was very different than with nondipole rolandic spikes. Children with dipole
      discharges less often presented with frequent seizures (10%), developmental delay
      (18%), school difficulties (34%), or abnormal neurological exam (22%). In
      contrast, children with nondipole rolandic discharges often presented with a
      history of frequent seizures (55%), developmental delay (55%), school
      difficulties (60%), and an abnormal neurological exam (63%). The incidence of
      clinical abnormalities in the nondipole group exceeded that found in our control
      population in all areas. Temporal-frontal dipole discharges are associated with a
      lower incidence of clinical abnormality than are nondipole rolandic spikes. These
      discharges may represent a benign functional focus.

PMID- 1370801
TI  - Aphasia as the sole manifestation of simple partial status epilepticus.
AB  - Aphasia due to simple partial status epilepticus is rare, particularly in the
      absence of a seizure history. No previous report describes acute aphasia as the
      sole clinical manifestation of EEG-monitored status epilepticus, with prompt
      resolution with treatment. We report a 45-year-old man with a left temporal
      glioblastoma who acutely developed a global aphasia, during which an EEG revealed
      continual repetitive sharp waves emanating from the left hemisphere. After
      injection of i.v. diazepam, the EEG seizure activity ceased, and the patient's
      language output returned to preseizure levels.

PMID- 1370802
TI  - The major Thiobacillus ferrooxidans outer membrane protein forms low conductance
      ion channels in planar lipid bilayers.
AB  - A protein isolated and purified from the outer membrane of the acidophilic,
      chemolithotrophic bacterium, Thiobacillus ferrooxidans with an oligomeric
      molecular weight of 90,000 Da (p90) was incorporated into
      phosphatidylethanolamine planar lipid bilayers. The protein formed slightly
      anionic channels in KCl solutions, with a conductance of 25 pS in 100 mM KCl. The
      current-voltage relationship was linear between +/- 60 mV, and the conductance
      was a saturating function of the salt concentration. These channels fluctuated
      from a single open to closed state at low potentials, but present flickering
      activity at higher potentials.

PMID- 1370803
TI  - The clearance of apoptotic cells in the liver is mediated by the
      asialoglycoprotein receptor.
AB  - Apoptosing cells are actively phagocytosed in parenchymal tissues, thus
      preventing the inflammatory reaction which could derive from their slow
      uncontrolled degradation. The molecular mechanisms by which an apoptotic cell is
      recognized and taken up are largely unknown. We propose that the recognition of
      apoptotic hepatocytes is mediated by the sugar recognition systems of the liver,
      particularly the asialoglycoprotein receptor (ASGP-R). The results presented here
      demonstrated the participation of ASGP-R in the removal of apoptotic parenchymal
      cells, and indicate a new perspective for the understanding of its physiological
      role.

PMID- 1370804
TI  - The major form of protein tyrosine kinase in the dog prostate is expressed by a
      50 kDa polypeptide.
AB  - We have already reported that the protein tyrosine kinase (PTK) activity in the
      dog prostate is distributed in cytosolic (75%) and particulate (Triton X-100
      solubilized) fractions and that upon gel filtration, both PTKs migrate as
      entities of Mr 44,000 [(1991) Biochem. Cell. Biol. 69, 146-153]. Herein we
      demonstrate by immunoprecipitation with anti-phosphotyrosine antibodies that the
      soluble PTK has the ability to undergo self-phosphorylation. In addition, the
      polypeptide responsible for that enzymatic activity has been identified by 2
      approaches: (1) a two-dimensional electrophoresis, in which the first dimension
      performed in non-denaturing conditions allowed the localization of the native
      enzyme, while the second dimension (SDS-PAGE) permitted the analysis of alkali
      resistant phosphoproteins corresponding to the activity; (2) protein renaturation
      after SDS-PAGE followed by in situ phosphorylation (with [gamma-32P]ATP) of
      polyGT electrophoresed together with the enzyme preparation; the exclusive
      presence of the radiolabeled phosphotyrosine in the renatured protein confirmed
      its enzymatic nature. Using these methods, the major form of PTK in the dog
      prostate was shown to be expressed by a 50 kDa polypeptide which possesses
      autophosphorylation sites and which is present in the cytosol as an active
      monomer.

PMID- 1370805
TI  - Tissue inhibitor of metalloproteinase-2 (TIMP-2) has erythroid-potentiating
      activity.
AB  - Tissue inhibitor of metalloproteinase (TIMP) was purified and molecularly cloned
      on the basis of its erythroid-potentiating activity (EPA). TIMP/EPA appears to be
      a bifunctional molecule with both growth factor and anti-enzymatic activity.
      Recently, a second TIMP-related molecule was identified and we have investigated
      its possible erythroid-potentiating activity. Native, purified human TIMP-2 was
      assayed for erythroid-potentiating activity using an in vitro erythroid burst
      formation assay and was compared with that of previously characterized
      recombinant EPA/TIMP-1. The results demonstrate that both members of the tissue
      inhibitor of metalloproteinase family, TIMP-1 and TIMP-2, possessed erythroid
      potentiating activity which was inhibited by antibodies developed to neutralize
      EPA. These results suggest that TIMP-2 shares a common structural domain with
      EPA/TIMP-1 that is responsible for the erythroid-potentiating activity of these
      inhibitors. Therefore, TIMP-1 and TIMP-2, with both anti-protease activity and
      growth factor activity, join a family of bifunctional molecules such as
      fibroblast growth factor and thrombin which have both enzymatic and growth factor
      activity.

PMID- 1370806
TI  - Biosynthesis of inter-alpha-trypsin inhibitor and alpha 1-microglobulin in a
      human hepatoma cell line.
AB  - 1. Biosynthesis of alpha 1-microglobulin and inter-alpha-trypsin inhibitor was
      investigated in a human hepatoma cell line HepG-2. 2. alpha 1-Microglobulin was
      translated as a precursor common with the light chain of inter-alpha-trypsin
      inhibitor. 3. alpha 1-Microglobulin was synthesized and secreted into the growth
      medium within 30 min. 4. Processing of inter-alpha-trypsin-inhibitor-related
      proteins appeared slow and incomplete. The light chain was connected via a
      chondroitinsulphate to a heavy chain to form a 125,000-Mr protein and secreted
      within 1-4 hr.

PMID- 1370807
TI  - Single-strand conformation polymorphism (SSCP) analysis of exon 11 of the CFTR
      gene reliably detects more than one third of non-delta F508 mutations in German
      cystic fibrosis patients.
AB  - In Central Europe, the delta F508 deletion accounts for approximately 75% of
      mutations in the cystic fibrosis transmembrane conductance regulator gene causing
      cystic fibrosis. The remainder comprise a large number of individually infrequent
      mutations whose detection requires a disproportionately large effort. However, a
      sizeable proportion of non-delta F508 mutations have been found to cluster within
      exon 11. We have taken advantage of this clustering to detect a total of five
      previously described point mutations present on 26/72 (36%) non-delta F508
      chromosomes by polymerase chain reaction/direct sequencing of exon 11. These exon
      11 mutations were then subjected to single-strand conformation polymorphism
      (SSCP) analysis, which was shown (i) to discriminate reliably between mutant and
      wildtype alleles and (ii) to generate reproducible mutation-specific band
      patterns. This analysis thus represents the first attempt to assess SSCP analysis
      retrospectively, and serves to illustrate the potential of this screening
      technique in diagnostic medicine.

PMID- 1370808
TI  - Cloning of the human alpha 2-macroglobulin gene and detection of mutations in two
      functional domains: the bait region and the thiolester site.
AB  - Overlapping genomic clones of the human alpha 2-macroglobulin (alpha 2M) gene
      were isolated from a cosmid library and were used to map 80 kb of the chromosomal
      region of this gene. Fragments carrying the two exons encoding the bait region
      and the exon encoding the thiolester site were partially sequenced and PCR
      primers were designed for the amplification of both functional domains. By direct
      genomic sequencing of these domains in 30 healthy individuals and in 30 patients
      with chronic lung disease three mutations were detected. The first was a sequence
      polymorphism occurring near the thiolester site of the gene, changing Val1000
      (GTC) to Ile1000 (ATC), with allele frequencies of 0.30 (GTC) and 0.70 (ATC),
      respectively. No difference of alpha 2M serum levels was observed for these two
      alleles. The second mutation occurred within the thiolester site of one patient,
      changing Cys972(TGT) to Tyr972(TAT). Since activation of the internal thiolester
      formed between Cys972 and Gln975 in each of the subunits of the tetrameric alpha
      2M is involved in the covalent cross-linking of the activating proteinase, this
      mutation is predicted to interfere with alpha 2M function. The alpha 2M serum
      level was within the normal range in this patient. In one healthy individual we
      detected an alteration of the bait region sequence, which is usually encoded by
      two different exons separated by an intron of size 1.6 kb. In this individual,
      PCR amplification of genomic DNA using the bait region primers produced the
      common fragment of size 1.8 kb and an additional variant fragment of size 0.23
      kb. This finding, and the genomic sequencing data of this individual, indicate
      that he carries two different alleles of the alpha 2M gene: one with the regular
      structure (bait exon I-intron-bait exon II), the other with the two bait exons
      fused into one. Direct genomic sequencing of the two alpha 2M functional domains
      is a useful tool for the detection of the genetic, and possibly the functional,
      heterogeneity of alpha 2M. This, in turn, may provide some insight into the
      hitherto unknown physiological role(s) of alpha 2M, by studying in vivo effects
      of naturally occurring mutations of the gene.

PMID- 1370809
TI  - A 27-bp deletion from one allele of the type III collagen gene (COL3A1) in a
      large family with Ehlers-Danlos syndrome type IV.
AB  - A large family with Ehlers-Danlos syndrome type IV (EDS IV) has previously been
      described. Unlike most cases of EDS IV, fibroblasts from affected members
      secreted near normal amounts of type III collagen. We have localized the mutation
      in this family to the CB5 peptide of type III collagen, by using both protein and
      cDNA mapping techniques. Sequence analysis of cDNA revealed a 27-bp deletion
      within exon 37, a deletion that removed nine amino acids and maintained the Gly-X
      Y repeat of the collagen helix. Further sequencing of genomic DNA confirmed its
      location, and amplification of DNA from family members showed that it was absent
      in unaffected individuals but present in all the affected individuals tested.
      This deletion is flanked by two short direct repeats of CTCC; it may have arisen
      by slipped mispairing, and has subsequently been transmitted to all affected
      family members.

PMID- 1370810
TI  - Dinucleotide (CA/GT) repeat polymorphism in intron 17B of the cystic fibrosis
      transmembrane conductance regulator (CFTR) gene.
AB  - We describe a polymorphic microsatellite (IVS17BCA) in intron 17B of the cystic
      fibrosis transmembrane conductance regulator (CFTR) gene. It consists of an 11 to
      20 CA/GT dinucleotide repeat, located 424 bp from exon 17B.

PMID- 1370811
TI  - Exon skipping in human beta-casein.
AB  - Earlier amino acid alignments of mature beta-caseins showed that the human
      protein was shifted in alignment relative to other species, with amino acid
      deletions in the N-terminal region and others inserted in the C-terminal region.
      Our alignment, based on cDNA sequences and their translation products, has shown
      that the amino acid deletions correspond exactly to exon 3 in the other species.
      Cloning and sequencing of a segment of the human beta-casein gene between exons 2
      and 4 revealed the presence of an intact exon 3 sequence in the gene. An
      interruption of the polypyrimidine tract adjacent to the 5' end of exon 3
      sequence may account for the omission of the exon from human beta-casein mRNA.

PMID- 1370812
TI  - A long-range repeat cluster in chromosome 1 of the house mouse, Mus musculus, and
      its relation to a germline homogeneously staining region.
AB  - The laboratory mouse C57BL genome contains about 50 copies of a long-range repeat
      DNA family clustered in the C-D region of chromosome 1. The repeat length is more
      than 50 kb and includes sequences homologous to at least two mRNAs. There are
      small differences in the copies of this repeat family such as restriction site
      mutations and gross differences like rearrangements and insertions of LINE1
      elements. A germline homogeneously staining region occurring as a chromosome 1
      polymorphism in many feral populations of the house mouse is an amplified version
      of this long-range repeat cluster.

PMID- 1370813
TI  - cDNA cloning for mouse thymocyte-activating molecule. A multifunctional ecto
      dipeptidyl peptidase IV (CD26) included in a subgroup of serine proteases.
AB  - Thymocyte-activating molecule (THAM) was initially characterized as a
      developmentally regulated, dimeric cell-surface molecule capable of activating
      mouse thymocytes and T lymphocytes upon monoclonal antibody (mAb)-mediated cross
      linking. We recently obtained structural evidence indicating that this molecule
      is the mouse homologue of the human T cell-activating ectoenzyme CD26 (dipeptidyl
      peptidase IV, DPP IV). We describe here the cloning and the characterization of
      THAM cDNA. Two clones (3.3 and 2.8 kilobases) were isolated. THAM-3.3 cDNA
      contains an open reading frame of 2,280 nucleotides that encodes a protein of 760
      amino acids having a calculated size of 87,500 Da. Complete N-glycosylation at
      each of the nine potential sites would result in a mature 110,000-Da molecule.
      Protein sequence comparisons revealed a significant homology (in particular in
      the COOH-terminal domain) between THAM and the rat or human DPP IV or the yeast
      dipeptidyl aminopeptidase B molecules (92, 85, and 30% sequence identity,
      respectively). Structural comparison of serine proteases (i.e. acyl-amino acid
      hydrolase or prolyl endopeptidase) with the most conserved domain of THAM
      identified a stretch of 200 amino acids containing a putative catalytic triad
      arranged in a novel topological order (Ser-624, Asp-702, and His-734) thereby
      defining a subfamily of nonclassical serine proteases. Expression of THAM during
      thymus ontogeny was found to be mainly regulated at the transcriptional level as
      determined by RNase protection assay. To investigate directly some of the
      functions which have been ascribed to DPP IV, we transfected an ovalbumin/Aq
      reactive, THAM- T hybridoma cell line with THAM-3.3 cDNA. The resultant
      transfectants acquired (i) DPP IV enzymatic activity that precisely paralleled
      the density of surface-expressed THAM; (ii) an Mr = 115,000 (reduced) and
      110,000/128,000 (nonreduced) molecule that could be immunoprecipitated by the
      THAM-specific mAb H194-112; and (iii) the capacity of being triggered by this mAb
      to release interleukin-2. These data indicate that a single cDNA species can
      encode a multifunctional molecule (e.g. activation signal-transducing structure
      and ectopeptidase), the heterodimeric state of which very likely results from a
      differential post-translational modification of the same protein core.

PMID- 1370814
TI  - The tRNA species for redundant genetic codons NNU and NNC. A thought on the
      absence of phenylalanine tRNA with AAA anticodon in Escherichia coli.
AB  - The redundant genetic codons NNU and NNC (where N is A, T, G, or C) specify the
      same amino acid and are decoded by their cognate tRNAs, which contain either a
      guanosine or a modified base in the wobble position of the anticodons. Since
      tRNAs with an adenosine in the wobble position of the anticodon, which are
      complementary to the NNU codons, are not found naturally, we have generated a
      tRNA(Phe) with AAA anticodon and examined how an adenosine in the wobble position
      would affect its biological function in Escherichia coli. We found that the
      tRNA(Phe) with GAA anticodon (wild-type) repressed the expression of the pheA
      gene via tRNA(Phe)-mediated attenuation of transcription, whereas the tRNA(Phe)
      with AAA anticodon did not influence the expression of the pheA gene.
      Furthermore, elevated levels of tRNA(Phe)(AAA) did not support the growth of an
      E. coli strain carrying a temperature-sensitive mutation in the pheS gene at 42
      degrees C. Since the presence of a multicopy plasmid carrying the gene that
      encodes tRNA(Phe)(GAA), a substrate for phenylalanyl tRNA synthetase, enables the
      E. coli strain carrying the pheS(Ts) mutation to grow at 42 degrees C, the above
      observation suggests that unlike tRNA(Phe)(GAA), tRNA(Phe)(AAA) is not a good
      substrate for phenylalanyl-tRNA synthetase. Therefore, we postulate that the
      presence of adenosine at the wobble position of anticodons was specifically
      eliminated and the tRNAs with guanosine or a modified base in the wobble position
      were selected to decode both NNU and NNC codons in E. coli.

PMID- 1370815
TI  - Binding of vitronectin-thrombin-antithrombin III complex to human endothelial
      cells is mediated by the heparin binding site of vitronectin.
AB  - The interaction of vitronectin-thrombin-antithrombin III (VN.TAT) complex with
      endothelial cells (EC) was investigated. Binding was specific and time- and
      concentration-dependent. Kinetics revealed an apparent dissociation constant of
      16 nM and 1.7 x 10(5) binding sites/endothelial cell. The binding determinant of
      the ternary complex was located on the VN moiety. Since the association of VN to
      TAT adds its specific properties to the VN.TAT complex, the involvement of the
      heparin binding domain and the cell attachment site of VN was investigated.
      Neither addition of RGD peptide nor blocking of the vitronectin receptor with a
      monoclonal antibody interfered with VN.TAT binding to EC. Addition of heparin, a
      VN-derived peptide comprising two heparin binding consensus sequences or a
      monoclonal antibody directed against the heparin binding domain on VN, completely
      inhibited VN.TAT binding to EC. These results indicate that the interaction is
      mediated through the heparin binding domain of VN. Digestion of heparan sulfate
      proteoglycans resulted in a decrease of VN.TAT binding to EC, indicating the
      involvement of heparin-like structures on the EC surface. Our findings point to
      an unrecognized mechanism by which VN may act as scavenger in order to enhance
      the clearance of end products of the clotting system via binding of the ternary
      VN.TAT complex to the luminal surface of EC.

PMID- 1370816
TI  - Regulation of basal and luminal cell-specific cytokeratin expression in rat
      accessory sex organs. Evidence for a new class of androgen-repressed genes and
      insight into their pairwise control.
AB  - Co-expression of cytokeratin (CK) pairs has been found to be associated with
      specific epithelial cell types whose expressions are developmentally regulated.
      In the prostate, CK 8 and 18 have been identified as luminal cell-specific
      markers, and CK 5 and 15 have been identified as basal cell-specific markers. In
      this study, we report the cloning and sequencing of a full-length CK 8 cDNA (1.9
      kilobases) from a rat ventral prostate (VP) cDNA library. Although the open
      reading frame shares 90% homology with mouse CK 8 sequences, nucleotide
      comparison revealed that rat CK 8 cDNA comprises a species-specific sequence on
      both 5' and 3' ends. The steady-state levels of CK 8 mRNA were elevated in VP,
      seminal vesicle (SV), and liver of a castrated rat but not in the other organs
      such as the coagulating gland, bladder, and thymus. Unlike the other androgen
      repressed genes, elevated CK 8 mRNA levels persisted even after the glandular
      involution was completed, indicating that CK 8 is a new class of androgen
      repressed gene. The regression of CK 8 expression may be androgen receptor
      mediated, since androgen but not estrogen administration to castrated hosts
      repressed the CK 8 mRNA levels, and this effect can be antagonized by the
      simultaneous administration of an antiandrogen (4-hydroxyflutamide).
      Immunohistochemical staining of prostatic tissues reveals that the CK 8
      filamentous structure is shifted reversibly from a uniform distribution to a
      predominantly basal surface upon androgen deprivation. We noted that the steady
      state levels of CK 8 protein remain rather constant throughout the various
      hormonal treatment, and the steady-state levels of CK 8 mRNA and the rate of CK 8
      protein synthesis are consistently elevated. These results suggest that the
      turnover rate of CK 8 protein may be elevated in the prostatic epithelium from
      the castrated host. Similarly, the steady-state levels of CK 15 and 18 mRNA in VP
      and SV are also repressed in an androgen-dependent manner. These data, taken
      together, indicate that pairwise control of luminal (and possibly basal) specific
      cytokeratin gene expression remains intact in both VP and SV tissues and that the
      levels of CK mRNAs expression are negatively regulated by androgen.

PMID- 1370817
TI  - Toxic effects of high levels of ppGpp in Escherichia coli are relieved by rpoB
      mutations.
AB  - A controversy has surrounded the questions of whether or not guanosine
      tetraphosphate (ppGpp) is a specific inhibitor of bacterial rRNA and tRNA
      synthesis, especially during normal exponential growth, and whether the RNA
      polymerase is the target of ppGpp action. To answer these questions, a pBR322
      derived plasmid, pKT28, was constructed that carries the Escherichia coli relA
      gene encoding a ppGpp synthetase under control of the lacUV5 promoter. The
      plasmid was used to transform the ppGpp reporter strain VH271 in which expression
      of beta-galactosidase from an rrnB P1 promoter is inhibited by ppGpp. In the
      presence of high concentrations of lac inducer, bacteria of the transformed
      strain accumulate ppGpp with the result that synthesis of rRNA and beta
      galactosidase is inhibited and growth ceases. At low concentrations of inducer,
      growth is only reduced and cells form small white colonies on X-gal indicator
      plates. After continued incubation, these colonies form blue sectors of faster
      growing mutant cells. Phage P1 transduction experiments showed that these mutants
      have mutations cotransducing with rpoB, the gene encoding the beta-subunit of RNA
      polymerase. One particular mutant strain, KT13, had acquired partial resistance
      to ppGpp inhibition of rRNA synthesis. The mutation in this strain was cloned by
      in vivo recombination into an rpoB plasmid. The presence of this plasmid
      conferred increased resistance to overproduction of ppGpp. These results suggest
      that ppGpp is a specific inhibitor of rRNA synthesis, even in the absence of
      amino acid starvation, and that RNA polymerase is involved as the target of ppGpp
      action.

PMID- 1370818
TI  - Translocation of alpha subunits of stimulatory guanine nucleotide-binding
      proteins through stimulation of the prostacyclin receptor in mouse mastocytoma
      cells.
AB  - The translocation of the alpha subunits of Gs from the membrane to the cytosol by
      iloprost, a stable prostacyclin analogue, was studied in mouse mastocytoma P-815
      cells. In the presence of guanosine 5'-O-(thiotriphosphate) (GTP gamma S),
      iloprost stimulated the adenylate cyclase activity, caused the release of both 42
      and 45-kDa proteins reactive with the anti Gs alpha carboxyl-terminal antibody,
      RM/1, from the membrane and attenuated cholera toxin-catalyzed ADP-ribosylation
      of the 42- and 45-kDa proteins in the membrane. The iloprost-stimulated adenylate
      cyclase activity and release of Gs alpha from the membrane were markedly
      suppressed by RM/1. Cholera toxin treatment also stimulated the adenylate cyclase
      activity and release of Gs alpha from the membrane, and iloprost synergistically
      potentiated these actions of cholera toxin. In mastocytoma cells, iloprost
      induced the translocation of both 42- and 45-kDa Gs alpha from the membrane to
      the cytosol, 45-kDa Gs alpha remaining in the cytosol for a longer time than 42-
      kDa Gs alpha. Whereas 42-kDa Gs alpha in the cytosol was eluted at the position
      of Mr = approximately 40,000 45-kDa Gs alpha was eluted at the position of Mr =
      approximately 120,000 from a Superose 12 gel filtration column. In contrast, both
      42- and 45-kDa Gs alpha released in vitro from the membrane by iloprost plus GTP
      gamma S were eluted at the position of Mr = approximately 40,000, but only 45-kDa
      Gs alpha was eluted at the position of Mr = approximately 120,000 when it was
      incubated with cytosol. These results taken together demonstrate that iloprost
      induces the translocation of both 42- and 45-kDa Gs alpha from the membrane to
      the cytosol and that only the 45-kDa Gs alpha released exists in the cytosol as a
      soluble complex with unidentified component(s) in mastocytoma cells.

PMID- 1370819
TI  - Influence of metal ions on the ribonuclease P reaction. Distinguishing substrate
      binding from catalysis.
AB  - A high yield, photoactivated cross-linking reaction between a modified tRNA and
      RNase P RNA was used as a quantitative assay of substrate binding affinity. The
      cross-linking assay allows the effects of metal ions on substrate binding to be
      measured independently and in the absence of the pre-tRNA cleavage reaction. The
      results of this assay, in conjunction with the conventional cleavage assay,
      support the following conclusions about the nature of the RNase P RNA-tRNA
      binding interaction. (i) Monovalent cations act primarily to enhance enzyme
      substrate binding, presumably by functioning as counterions. This enhancement can
      be attributed to a reduction in the tRNA off-rate. (ii) Although divalent cation
      is required for cleavage, the enzyme-substrate complex can form in the absence of
      divalent cation; the essential role of divalent cation in the reaction is thus
      catalytic. (iii) Ca2+ is as efficient as Mg2+ in promoting binding but supports
      catalysis only at a low rate.

PMID- 1370820
TI  - Direct linkage of three tachykinin receptors to stimulation of both
      phosphatidylinositol hydrolysis and cyclic AMP cascades in transfected Chinese
      hamster ovary cells.
AB  - The mammalian tachykinin system consists of three distinct peptides, substance P,
      substance K, and neuromedin K, and possesses three corresponding receptors. In
      this investigation we examined intracellular signal transduction of the
      individual tachykinin receptors by transfection and stable expression of these
      receptor cDNAs in Chinese hamster ovary cells. The three receptors commonly
      showed a rapid and marked stimulation in both phosphatidylinositol (PI)
      hydrolysis and cyclic AMP formation in response to tachykinin interaction. Direct
      linkage of the three receptors to both phospholipase C and adenylate cyclase was
      evidenced by the finding that tachykinin, added together with GTP, activated
      these enzyme activities in membrane preparations derived from tachykinin receptor
      expressing cells. The stimulation of cyclic AMP formation was less efficient than
      that of PI hydrolysis in receptor-expressing cells as well as their membrane
      preparations (about 1 order of magnitude difference in the effective peptide
      concentrations). However, the stimulatory responses of the PI hydrolysis and
      cyclic AMP formation in both receptor-expressing cells and their membrane
      preparations were induced in complete agreement with the tachykinin binding
      selectivity of each subtype of the receptors. This investigation demonstrated
      unequivocally that the tachykinin receptors have the potential to couple directly
      to both phospholipase C and adenylate cyclase and to stimulate PI hydrolysis and
      cyclic AMP formation.

PMID- 1370821
TI  - A 130-kDa protein on endothelial cells binds to amino acids 15-42 of the B beta
      chain of fibrinogen.
AB  - Factors which stimulate the release of von Willebrand factor (vWf) from
      endothelial cell Weibel-Palade bodies and which induce the expression of the
      leukocyte-binding adhesion molecule P-selectin (PADGEM, GMP-140, CD62) on the
      endothelial cell surface remain incompletely characterized. Fibrin but not
      fibrinogen is a potent stimulus for the release of stored von Willebrand factor
      from endothelial cells. Removal of fibrinopeptides A and B from fibrinogen occurs
      during the formation of fibrin, and the removal of fibrinopeptide B is a
      requirement for fibrin to induce vWf secretion. The cleavage of fibrinopeptide A
      by reptilase enzyme forms a fibrin gel yet it is incapable of stimulating Weibel
      Palade body degranulation. As a consequence of removing fibrinopeptide B, B beta
      15-42 becomes the new NH2 terminus of the beta chain of fibrin. We have shown
      that the peptide B beta 15-42 in solution inhibits the release of vWf stimulated
      by fibrin. In addition, B beta 15-42 coupled to ovalbumin supports the binding
      and spreading of endothelial cells, while a scrambled form of this peptide
      coupled to the same carrier does not. We investigated whether these determinants
      near the amino terminus of the beta chain of fibrin bind to a specific protein on
      the surface of endothelial cells. A 130-kDa protein was isolated from surface
      labeled human umbilical vein endothelial cells by specific binding to B beta 15
      42 immobilized on Sepharose. This glycoprotein was eluted with the B beta 15-42
      peptide in solution but not with the scrambled form of this peptide. The fibrin
      derived peptides B beta 19-26 and B beta 37-56-cysteine were also incapable of
      eluting the 130-kDa protein bound to immobilized B beta 15-42 as were the
      arginine-glycine-aspartic acid-serine RGDS tetrapeptide and EDTA. The 130-kDa
      protein is recognized neither by antibodies to the known integrins found on
      endothelial cells nor by antibodies to CD31 (endoCAM, PECAM-1), a member of the
      immunoglobulin family of receptors found on endothelial cells. The beta chain of
      fibrin thus contains a sequence near its amino terminus which specifically binds
      to what is likely a novel endothelial cell surface protein. This glycoprotein may
      promote endothelial cell adhesion to fibrin during the wound healing process and
      is a candidate for a receptor involved in fibrin-mediated release of Weibel
      Palade bodies from endothelial cells.

PMID- 1370822
TI  - DNA strand scission and free radical production in menadione-treated cells.
      Correlation with cytotoxicity and role of NADPH quinone acceptor oxidoreductase.
AB  - Menadione (MD; 2-methyl-1,4-naphthoquinone), a redox cycling quinone was shown to
      induce single (ss)- and double (ds)-strand DNA breaks in human MCF-7 cells. This
      DNA damage was mediated via the hydroxyl radical as evidenced by electron spin
      resonance spectroscopy (ESR) studies utilizing the spin trap, 5,5-dimethyl-1
      pyrroline-1-oxide. The free radical production and DNA damage were shown to play
      a role in MD cytotoxicity as revealed by the reversal of MD toxicity and
      inhibition of hydroxyl radical production by exogenously added catalase. The role
      of NADPH quinone acceptor oxidoreductase in the metabolism of MD was evaluated.
      Purified quinone acceptor oxidoreductase in combination with MD resulted in the
      production of significant levels of the hydroxyl radical as measured by ESR.
      Dicumarol, an inhibitor of quinone acceptor oxidoreductase, decreased the
      production of the hydroxyl radical and attenuated DNA strand breaks in MCF-7
      cells treated with MD.

PMID- 1370823
TI  - Pore-forming activity of OmpA protein of Escherichia coli.
AB  - Escherichia coli outer membrane protein OmpA was purified to homogeneity, as a
      monomer, from a K12 derivative deficient in both OmpF and OmpC porins. When
      proteoliposomes reconstituted from the purified OmpA, phospholipids, and lithium
      dodecyl sulfate were tested for permeability to small molecules by osmotic
      swelling, it was found that OmpA produced apparently nonspecific diffusion
      channels that allowed the penetration of various solutes. The pore-forming
      activity was destroyed by the heat denaturation of the OmpA protein, and the use
      of an OmpA-deficient mutant showed that the activity was not caused by
      copurifying contaminants. The size of the OmpA channel, estimated by comparison
      of diffusion rates of solutes of different sizes, was rather similar to that of
      E. coli OmpF and OmpC porins, i.e. about 1 nm in diameter. The rate of
      penetration of L-arabinose caused by a given amount of OmpA protein, however, was
      about a hundredfold lower than the rate produced by the same amount of E. coli
      OmpF porin. The addition of large amounts of lithium dodecyl sulfate to the
      reconstitution mixture increased the permeability through the OmpA channel,
      apparently by facilitating the correct insertion of OmpA into the bilayer.

PMID- 1370824
TI  - Characterization of lysyl residues of NADH-cytochrome b5 reductase implicated in
      charge-pairing with active-site carboxyl residues of cytochrome b5 by site
      directed mutagenesis of an expression vector for the flavoprotein.
AB  - An expression vector for bovine NADH-cytochrome b5 reductase was constructed from
      two DNA fragments that were derived from beef liver poly(A+) RNA using the
      polymerase chain reaction. Site-directed mutagenesis of the 3 lysine residues of
      the reductase, previously implicated in the formation of active-site charge pairs
      with carboxylate residues of cytochrome b5, was then used to obtain the purified
      catalytic domains of flavoproteins modified at each of these sites. The observed
      marked decreases in catalytic efficiencies of substitutions of a negative charge
      at the normally positively charged residues with the catalytic domain of
      cytochrome b5 are consistent with their participation in the formation of charge
      pairs with carboxylate groups of the hemeprotein to optimize rapid electron
      transfer from the reductase flavin to the heme of the cytochrome.

PMID- 1370825
TI  - Isolation of a cDNA encoding a human serum marker for acute pancreatitis.
      Identification of pancreas-specific protein as pancreatic procarboxypeptidase B.
AB  - A human pancreas-specific protein (PASP), previously characterized as a serum
      marker for acute pancreatitis and pancreatic graft rejection, has been identified
      as pancreatic procarboxypeptidase B (PCPB). cDNAs encoding PASP/PCPB were
      isolated from a human pancreas cDNA library using a combination of nucleic acid
      hybridization screening and immunoscreening with antisera raised against native
      PASP. The deduced amino acid sequence of PASP/PCPB cDNA predicts the translation
      of a 416-amino acid preproenzyme with a 15-amino acid signal/leader peptide and a
      95-amino acid activation peptide. The proenzyme portion of this protein has 76%
      identity with rat PCPB and 84% identity with bovine carboxypeptidase B. DNA and
      RNA blot analyses indicate that human PCPB mRNA (1,400 nucleotides) is
      transcribed from a single locus in the human genome in a tissue-specific fashion.
      N-terminal sequencing of native PASP and the specific immunoreactivity of
      bacterially expressed PASP/PCPB with native PASP antibodies confirm the
      identification of PASP as human pancreatic PCPB.

PMID- 1370826
TI  - Inhibition of growth by transforming growth factor-beta following fusion of two
      nonresponsive human carcinoma cell lines. Implication of the type II receptor in
      growth inhibitory responses.
AB  - Loss of growth regulation by transforming growth factor-beta (TGF-beta) may be an
      important step in carcinogenesis. We have used a cell fusion system to show that
      inhibition of growth by TGF-beta can be restored to carcinoma cell lines that are
      unresponsive to the inhibitory effects of TGF-beta. In a previous study, the EJ
      bladder carcinoma line was fused to the SW480 colon adenocarcinoma line and found
      to produce nontumorigenic hybrid cells along with one hybrid cell clone of low
      tumorigenicity. Here we show that the capacity of the nontumorigenic hybrid cells
      to respond to either TGF-beta 1 or TGF-beta 2 has been restored, while the
      parental or tumorigenic hybrid cells show little or no inhibition of growth
      following TGF-beta treatment. Cross-linking analyses with labeled TGF-beta 1
      demonstrated much higher levels of the type II (85 kDa) receptor in the hybrid
      cells compared with the parental tumor lines. Both the parental and tumorigenic
      hybrid cell lines were capable of responding to TGF-beta as evidenced by
      increased levels of mRNA for fibronectin, type IV collagenase, and plasminogen
      activator inhibitor after treatment with TGF-beta 1. These results suggest that
      the type II receptor is necessary for mediating the effects of TGF-beta on
      inhibition of growth but not on gene activation of the hybrid cells.

PMID- 1370827
TI  - Molecular cloning and characterization of human fetal liver tropomodulin. A
      tropomyosin-binding protein.
AB  - Human erythrocyte tropomodulin is a novel tropomyosin regulatory protein that
      binds to the end of erythrocyte tropomyosin and blocks heat-to-tail association
      of tropomyosin along actin filaments. It has been proposed to play a role in
      modulating the association of tropomyosin with the spectrin-actin complex in the
      erythrocyte membrane skeleton. Immunoscreening of a human fetal liver cDNA
      expression library in lambda gt11, followed by 5'-end extension by polymerase
      chain reaction from the same library, yielded a composite cDNA sequence of 2665
      base pairs (bp). It contains a 34-bp 5'-untranslated region, a 1.6-kilobase (kb)
      3'-untranslated region, and a complete open reading frame of 1077 bp that encodes
      a protein of 359 amino acids with a calculated molecular mass of 40.6 kDa and a
      pI of 4.8. Authenticity of the tropomodulin cDNA was confirmed by a complete
      sequence match of 49 predicted amino acids with the sequences of three tryptic
      peptides of the erythrocyte tropomodulin. The sequence has no internal repeats
      and no significant homology with any known proteins. Secondary structure
      predictions indicate that tropomodulin may consist of a series of seven or eight
      short alpha-helical segments and fold into a somewhat compact shape. The
      tropomyosin binding activity has been mapped to an N-terminal region containing
      residues 39-138. Nine independent PCR clones, five from a human reticulocyte cDNA
      library and four from the fetal liver cDNA library, revealed identical N-terminal
      103 amino acids, suggesting that the sequence reported here may also be of
      erythrocyte tropomodulin. Northern analysis of human reticulocyte RNA showed two
      hybridizing bands of 2.7 and 1.6 kb, indicating that the 2665-bp cDNA sequence
      reported here was that of the longer transcript.

PMID- 1370828
TI  - Base mispair extension kinetics. Binding of avian myeloblastosis reverse
      transcriptase to matched and mismatched base pair termini.
AB  - We investigate the enzymatic basis for the inefficient extension of single base
      mismatches by DNA polymerase compared with the extension of correct base pairs.
      Inefficient mismatch extension could result from either a reduced binding of the
      enzyme to mispaired versus correctly paired DNA template-primer termini, or from
      a lowered intrinsic rate of extension of mispairs by a bound enzyme, or from a
      combination of both factors. Avian myeloblastosis reverse transcriptase is used
      to measure the affinities (equilibrium dissociation constants) for the four
      matched and twelve mismatched base pair configurations situated at a primer 3'
      terminus. The binding affinities are analyzed by two different assays employing
      polyacrylamide gels. The first assay uses steady-state kinetics to measure the
      efficiency of elongating correct and incorrect base pairs and to evaluate the
      enzyme's dissociation constants for matched and mismatched termini. The estimated
      KD values obtained in the steady-state analysis fall within a range of
      approximately 0.1-20 nM. The efficiencies of extending two of the mispairs, G.G
      and C.C, are too low to allow a determination of KD by the kinetics method. The
      second assay uses equilibrium binding to measure the ratio of polymerase bound to
      matched compared with mismatched termini, KDright/KDwrong. The affinity ratios,
      including values for G.G and C.C mispairs, are in the range of about 0.4-4.2.
      While around 1 order of magnitude difference is observed in the relative binding
      affinities of the polymerase for matched and mismatched primer termini, the
      relative extension efficiencies vary over more than 5 orders of magnitude.
      Therefore, it appears that inefficient mismatch extension is caused primarily by
      a kinetic block inhibiting elongation from mispaired primer 3'-termini rather
      than to a difference in binding.

PMID- 1370829
TI  - Neonatal rat submandibular gland protein SMG-A and parotid secretory protein are
      alternatively regulated members of a salivary protein multigene family.
AB  - Submandibular gland-A (SMG-A) is a major secretory product of the neonatal rat
      submandibular gland but is not synthesized by the acinar cells of the adult
      gland. The leucine-rich protein is a predominant product of the adult rat parotid
      gland. Preliminary data had indicated that the leucine-rich protein and SMG-A
      might be identical proteins whose expression was differently regulated in the
      parotid and submandibular salivary glands. cDNA clones encoding SMG-A and the
      leucine-rich protein were identified by homology to a major mouse parotid gland
      product, parotid secretory protein (PSP), and characterized. The leucine-rich
      protein shares extensive sequence homology with mouse PSP throughout its 5'
      untranslated, protein coding and 3'-untranslated regions, prompting our
      suggestion that it should henceforth be referred to as rat PSP. SMG-A is more
      divergent, having greatest identity with rat and mouse PSP in its signal peptide
      and 3'-untranslated sequences. Transcripts homologous to SMG-A and rat PSP, but
      more closely related to SMG-A, were identified in rat sublingual gland by
      Northern blot analysis. These findings indicate that rat SMG-A and PSP arise from
      alternatively regulated members of a multigene family.

PMID- 1370830
TI  - Altered regulation of a major substrate of protein kinase C in rat 6 fibroblasts
      overproducing PKC beta I.
AB  - We have shown previously that the stable overproduction of protein kinase C beta
      I (cPKC beta I) in rat 6 (R6) embryo fibroblasts results in multiple cellular
      growth abnormalities. To characterize the pathways through which cPKC beta I acts
      to exert its effects, we have undertaken a biochemical analysis of the cell line
      R6-PKC3. The subcellular distribution of cPKC beta I in unstimulated R6-PKC3
      cells was approximately 80% cytosolic and approximately 20% membrane bound, and
      treatment of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted
      in translocation and down-regulation of an appreciable fraction of the cPKC beta
      I enzyme. However, long term TPA treatment was not sufficient to down-regulate
      all of the overproduced enzyme from both the cytosolic and membrane fractions.
      Two-dimensional gel analysis of 32P-labeled cellular phosphoproteins from either
      untreated or TPA-treated cultures revealed only minor qualitative differences
      between R6-PKC3 cells and a vector control cell line, R6-C1. On the other hand,
      several quantitative differences in the level of phosphorylation of discrete
      protein spots were seen. The most prominent phosphoprotein was a previously
      described 80/87-kDa protein designated MARCKS (myristoylated alanine-rich C
      kinase substrate). Compared with R6-C1 cells, R6-PKC3 cells exhibited a 2-3-fold
      increase in the basal level of phosphorylation of MARCKS and after treatment with
      TPA, displayed a dramatic prolongation in phosphorylation of this protein.
      Additionally, treatment of R6-PKC3 cells with TPA led to a prolonged increase in
      both the cytosolic and total cellular level of the MARCKS protein and a
      pronounced decrease in the level of MARCKS mRNA. Taken together, these results
      indicate that overproduction of cPKC beta I markedly alters several parameters of
      the MARCKS protein which may be responsible, at least in part, for the altered
      phenotype of these cells.

PMID- 1370831
TI  - Identification of a protein-binding site in the promoter of the human thymidine
      kinase gene required for the G1-S-regulated transcription.
AB  - When quiescent cells are stimulated to enter the cell cycle, the thymidine kinase
      (TK) gene is transcriptionally activated at the border of G1 and S. In this
      report we show that the human TK promoter contains multiple protein-binding
      sites. By site-directed mutagenesis, we identified a protein-binding site on the
      human TK promoter required for conferring G1-S-regulated transcription to a
      heterologous promoter and dissociated it functionally from an adjacent protein
      binding domain containing an inverted CCAAT motif required for high basal level
      expression. Substitution-mutation of this site results in constitutive expression
      of the neo reporter gene in serum-stimulated fibroblasts, as well as in cells
      arrested in mid-G1 by a temperature-sensitive mutation. The regulatory domains
      for the human TK promoter exhibit interesting symmetrical features, including a
      set of CCAAT motifs and sites similar to the novel Yi protein-binding site
      recently discovered in the mouse TK promoter.

PMID- 1370832
TI  - Anti-idiotypic antibodies against an antibody to the platelet glycoprotein (GP)
      IIb-IIIa complex mimic GP IIb-IIIa by recognizing fibrinogen.
AB  - Binding of the adhesive ligand fibrinogen and the monoclonal antibody PAC1 to
      platelet glycoprotein (GP) IIb-IIIa is dependent on cell activation and inhibited
      by Arg-Gly-Asp (RGD)-containing peptides. Previously, we identified a sequence in
      a hypervariable region of PAC1 (mu-CDR3) that mimics the activity of the
      antibody. Here we examine whether monoclonal antibodies to this idiotypic
      determinant in PAC1 can mimic GP IIb-IIIa by binding to fibrinogen. Mice were
      immunized with a peptide derived from the mu-CDR3 of PAC1. Four antibodies were
      obtained that recognized fibrinogen as well as a recombinant form of the variable
      region of PAC1. However, they did not bind to other RGD-containing proteins,
      including von Willebrand factor, fibronectin, and vitronectin. Several studies
      suggested that these anti-PAC1 peptide antibodies were specific for GP IIb-IIIa
      recognition sites in fibrinogen. Three such sites have been proposed: two RGD
      containing regions in the A alpha chain, and the COOH terminus of the gamma chain
      (gamma 400-411). Two of the antibodies inhibited fibrinogen binding to activated
      platelets, and all four antibodies bound to the fibrinogen A alpha chain on
      immunoblots. Antibody binding to immobilized fibrinogen was partially inhibited
      by monoclonal antibodies specific for the two A alpha chain RGD regions. However,
      the anti-PAC1 peptide antibodies also bound to plasmin-derived fibrinogen
      fragments X and D100, which contain gamma 400-411 but lack one or both A alpha
      RGD regions. This binding was inhibited by an antibody specific for gamma 400
      411. When fragment D100 was converted to D80, which lacks gamma 400-411, antibody
      binding was reduced significantly (p less than 0.01). Electron microscopy of
      fibrinogen-antibody complexes confirmed that each antibody could bind to sites on
      the A alpha and gamma chains. These studies demonstrate that certain anti-PAC1
      peptide antibodies mimic GP IIb-IIIa by binding to platelet recognition sites in
      fibrinogen. Furthermore, they suggest that the gamma 400-411 region of fibrinogen
      may exist in a conformation similar to that of an A alpha RGD region of the
      molecule.

PMID- 1370833
TI  - The structure of the human interferon alpha/beta receptor gene.
AB  - Using the cDNA coding for the human interferon alpha/beta receptor (IFNAR), the
      IFNAR gene has been physically mapped relative to the other loci of the
      chromosome 21q22.1 region. 32,906 base pairs covering the IFNAR gene have been
      cloned and sequenced. Primer extension and solution hybridization-ribonuclease
      protection have been used to determine that the transcription of the gene is
      initiated in a broad region of 20 base pairs. Some aspects of the polymorphism of
      the gene, including noncoding sequences, have been analyzed; some are allelic
      differences in the coding sequence that induce amino acid variations in the
      resulting protein. The exon structure of the IFNAR gene and of that of the
      available genes for the receptors of the cytokine/growth
      hormone/prolactin/interferon receptor family have been compared with the
      predictions for the secondary structure of those receptors. From this analysis,
      we postulate a common origin and propose an hypothesis for the divergence from
      the immunoglobulin superfamily.

PMID- 1370834
TI  - Selective action of 2',3'-didehydro-2',3'-dideoxythymidine triphosphate on human
      immunodeficiency virus reverse transcriptase and human DNA polymerases.
AB  - This study used DNA primer extension and sequencing gel analyses to evaluate the
      molecular action of 2',3'-didehydro-2',3'-dideoxythymidine triphosphate (D4TTP),
      in comparison with 3'-azido-2',3'-dideoxythymidine triphosphate (AZTTP), on DNA
      strand elongation by human immunodeficiency virus reverse transcriptases (HIV-RT)
      and human DNA polymerases alpha (pol alpha) and epsilon (pol epsilon) purified
      from T-lymphoblastoid CEM cells. D4TTP was preferentially incorporated into the T
      sites of the elongating DNA strand by HIV-RT and terminated DNA synthesis at the
      incorporation sites. The DNA chain termination activity of D4TTP was equipotent
      to that of AZTTP. In contrast, D4TTP was a poor substrate for pol alpha and pol
      epsilon. The analogue was incorporated into DNA by the human enzymes about 10,000
      to 20,000-fold less efficiently than by HIV-RT, whereas the incorporation of
      AZTTP by pol alpha and pol epsilon was not detectable by the DNA primer extension
      assay. Pol epsilon, an enzyme with 3'----5'-exonuclease activity, was unable to
      remove the incorporated 2',3'-didehydro-2',3'-dideoxythymidine monophosphate
      (D4TMP) from the 3'-end of the DNA strand, whereas 3'-azido-2',3'
      dideoxythymidine monophosphate was excised from DNA by pol epsilon at about 20%
      of the rate for normal deoxynucleotide excision. The preferential incorporation
      of D4TTP by HIV-RT appears to be a molecular basis for the selective anti-HIV
      activity of D4T, whereas the inability of pol epsilon to remove D4TMP from DNA
      may be related to the cytotoxicity of this compound.

PMID- 1370835
TI  - pp60src tyrosine kinase modulates P19 embryonal carcinoma cell fate by inhibiting
      neuronal but not epithelial differentiation.
AB  - P19 embryonal carcinoma cells provide an in vitro model system to analyze the
      events involved in neural differentiation. These multipotential stem cells can be
      induced by retinoic acid (RA) to differentiate into neural cells. We have
      investigated the ability of several variant forms of the protein-tyrosine kinase
      (PTK) pp60src to modulate cell fate determination in this system. Normally, P19
      cells are induced to differentiate along a neural lineage when allowed to form
      extensive cell-cell contacts in large multicellular aggregates during exposure to
      RA. Through analysis of markers of epithelial (keratin and desmosomal proteins)
      and neuronal (neurofilament) cells we have found that RA-induced P19 cells
      transiently express epithelial markers before neuronal differentiation. Under
      these inductive conditions, expression of pp60v-src or expression of the neuronal
      variant pp60c-src+ inhibited neuronal differentiation, and resulted in maintained
      expression of an epithelial phenotype. Morphological analysis showed that
      expression of pp60src PTKs results in decreased cell-cell adhesion during the
      critical cell aggregation stage of the neural differentiation procedure. The
      effects of pp60v-src on cell fate and cell-cell adhesion could be mimicked by
      direct modulation of Ca+(+)-dependent cell-cell contact during RA induction of
      normal P19 cells. We conclude that the neural lineage of P19 cells includes an
      early epithelial intermediate and suggest that tyrosine phosphorylation can
      modulate cell fate determination during an early cell-cell adhesion-dependent
      event in neurogenesis.

PMID- 1370836
TI  - The hyaluronan receptor (CD44) participates in the uptake and degradation of
      hyaluronan.
AB  - The hyaluronan receptor belongs to the polymorphic family of CD44 glycoproteins,
      which have been implicated in a variety of cellular functions including adhesion
      to hyaluronan and collagen, the binding of lymphocytes to high endothelial cells
      during extravasation, and conferring metastatic potential to carcinoma cells.
      Here, we demonstrate that the receptor also participates in the uptake and
      degradation of hyaluronan by both transformed fibroblasts (SV-3T3 cells) and
      alveolar macrophages. These cells were incubated with isotopically labeled
      hyaluronan for various periods of time, and the extent of degradation was
      determined by either molecular-sieve chromatography or centrifugation through
      Centricon 30 microconcentrators. The macrophages degraded the hyaluronan at a
      faster rate than the SV-3T3 cells, which may reflect the fact that they contained
      a greater number of receptors. More importantly, in both cell types, the
      degradation of hyaluronan was specifically blocked by antibodies directed against
      the receptor. However, the receptor by itself did not have the ability to degrade
      hyaluronan, since preparations of SV-3T3 membranes containing the receptor did
      not break down hyaluronan. Subsequent experiments revealed that macrophages can
      internalize fluorescein-tagged hyaluronan, and this process was blocked by
      antibodies against the receptor. Furthermore, the subsequent degradation of
      hyaluronan was inhibited by agents that block the acidification of lysosomes
      (chloroquine and NH4Cl). Thus, the most likely explanation for these results is
      that the receptor mediates the uptake of hyaluronan into the cell where it can be
      degraded by acid hydrolases in lysosomes. The ability of cells expressing the
      receptor to degrade hyaluronan may be important during tissue morphogenesis and
      cell migration.

PMID- 1370837
TI  - Interactions of the neural cell adhesion molecule and the myelin-associated
      glycoprotein with collagen type I: involvement in fibrillogenesis.
AB  - To gain insights into the functional role of the molecular association between
      neural adhesion molecules and extracellular matrix constituents, soluble forms of
      the myelin-associated glycoprotein (MAG) and the neural cell adhesion molecule (N
      CAM), representing most of the extracellular domains of the molecules, were
      investigated in their ability to modify fibrillogenesis of collagen type I. MAG
      and N-CAM retarded the rate of fibril formation, as measured by changes in
      turbidity, and increased the diameter of the fibrils formed, but did not change
      the banding pattern when compared to collagen type I in the absence of adhesion
      molecules. Scatchard plot analysis of the binding of MAG and N-CAM to the fibril
      forming collagen types I, II, III, and V suggest one binding site for N-CAM and
      two binding sites for MAG. Binding of MAG, but not of N-CAM, to collagen type I
      was decreased during fibril formation, probably due to a reduced accessibility of
      one binding site for MAG during fibrillogenesis. These results indicate that the
      neural adhesion molecules can influence the configuration of extracellular matrix
      constituents, thus, implicating them in the modulation of cell-substrate
      interactions.

PMID- 1370838
TI  - Identification and characterization of an actin-binding site of CapZ.
AB  - A mAb (1E5) that binds the COOH-terminal region of the beta subunit of chicken
      CapZ inhibits the ability of CapZ to bind the barbed ends of actin filaments and
      nucleate actin polymerization. CapZ prepared as fusion proteins in bacteria or
      nonfusion proteins by in vitro translation has activity similar to that of CapZ
      purified from muscle. Deletion of the COOH-terminus of the beta subunit of CapZ
      leads to a loss of CapZ's ability to bind the barbed ends of actin filaments. A
      peptide corresponding to the COOH-terminal region of CapZ beta, expressed as a
      fusion protein, binds actin monomers. The mAb 1E5 also inhibits the binding of
      this peptide to actin. These results suggest that the COOH-terminal region of the
      beta subunit of CapZ is an actin-binding site. The primary structure of this
      region is not similar to that of potential actin-binding sites identified in
      other proteins. In addition, the primary structure of this region is not
      conserved across species.

PMID- 1370840
TI  - Keratinocytes stimulate prostaglandin I2 synthesis by 3T3 cells and exhibit
      enhanced cornification when exposed to prostaglandin I2 analogues.
AB  - The predominant cyclooxygenase products of keratinocytes are prostaglandin (PG)E2
      and PGF2 alpha with only trace amounts of PGI2 synthesis detected. When normal or
      immortal (NM1) keratinocytes were co-cultured with mitomycin C-treated 3T3 cells,
      increased synthesis of PGI2 was noted compared to mitomycin C-treated 3T3 cells
      alone. The PGI2 level in co-cultures was maximum within the first week and
      diminished rapidly thereafter. These results suggested keratinocytes enhance the
      production of PGI2 by 3T3 cells. Keratinocyte cultures incubated with Iloprost
      and Piriprost, stable PGI2 analogues, showed evidence of increased cornification
      as demonstrated by staining with rhodanile blue, decreased shedding of cells into
      the culture medium, and more cornified material adhering to the culture surface.
      The cultures appeared to be responsive between the first and second weeks after
      plating and the inhibition of shedding could not be reversed by changing to drug
      free medium. Control and treated cultures showed identical electrophoretic
      protein patterns. Immunoblots showed involucrin unchanged in extracts of control
      and treated cultures while the 22 kd pancornulin was absent in treated cultures.
      The findings that keratinocytes enhance the production of PGI2 by 3T3 cells and
      that PGI2 analogues enhance cornification of confluent keratinocytes raise the
      possibility that eicosanoids may serve as autoregulatory signals together with
      other factors.

PMID- 1370841
TI  - Serotonin produces a configurational change of cultured smooth muscle cells that
      is associated with elevation of intracellular cAMP.
AB  - Early passaged bovine pulmonary artery smooth muscle cells (SMC) respond to
      serotonin (5-HT) by developing a reversible change in configuration. (Lee et al.
      J. Cell. Physiol. 138:145, 1989). This configurational change does not occur in
      pulmonary artery endothelial cells (EC) subjected to 5-HT and is adenosine
      triphosphate (ATP) dependent, lost with passage of SMC, and inhibited by various
      agents that block high-affinity 5-HT uptake. We now report a second
      configurational change (also dendritic formation) of SMC produced by 5-HT only in
      the presence of isobutylmethylxanthine (IBMX), an inhibitor of phosphodiesterase.
      This configurational change was also ATP dependent, but unlike the first
      response, (Lee et al., 1989), it occurred in both first and later passaged SMC
      and was not inhibited by blockade of 5-HT uptake. Also, unlike the response with
      5-HT alone that failed to elevate cAMP, this one was associated with a large
      elevation of cAMP (eight fold above control values), similar to the response to
      the beta-agonist isoproterenol, plus IBMX. The second response was not blocked by
      a variety of 5-HT receptor antagonists but was reproduced by (+/-)-8-hydroxy-DPAT
      HBr (8-OH-DPAT), a reputed 5-HT1A agonist. The response was not dependent upon
      Ca2+ and was blocked by 1-2 mM n-phenylanthranilic acid or anthracene-9
      carboxylic acid, electrically conductive Cl- channel inhibitors. Hence, 5-HT in
      the presence of IBMX causes a marked elevation of cAMP of SMC and this elevation
      in cAMP likely results in a cellular configurational change through a Cl- channel
      dependent mechanism similar to that we previously described for EC in the
      presence of beta-adrenergic agonist stimulation (Ueda et al. Circ. Res. 66:951,
      1990). EC do not show a similar response to 5-HT possibly because cAMP is not
      adequately elevated, even in the presence of IBMX, to enhance Cl- channel
      activity. We propose that our observations indicate the presence of two sites of
      action of 5-HT on the smooth muscle cell, one intracellularly and another at a
      cell surface receptor.

PMID- 1370839
TI  - Micromanipulation of adhesion of a Jurkat cell to a planar bilayer membrane
      containing lymphocyte function-associated antigen 3 molecules.
AB  - Cell adhesion plays a fundamental role in the organization of cells in
      differentiated organs, cell motility, and immune response. A novel
      micromanipulation method is employed to quantify the direct contribution of
      surface adhesion receptors to the physical strength of cell adhesion. In this
      technique, a cell is brought into contact with a glass-supported planar membrane
      reconstituted with a known concentration of a given type of adhesion molecules.
      After a period of incubation (5-10 min), the cell is detached from the planar
      bilayer by pulling away the pipette holding the cell in the direction
      perpendicular to the glass-supported planar bilayer. In particular, we
      investigated the adhesion between a Jurkat cell expressing CD2 and a glass
      supported planar bilayer containing either the glycosyl-phosphatidylinositol
      (GPI) or the transmembrane (TM) isoform of the counter-receptor lymphocyte
      function-associated antigen 3 (LFA-3) at a concentration of 1,000
      molecules/microns 2. In response to the pipette force the Jurkat cells that
      adhered to the planar bilayer containing the GPI isoform of LFA-3 underwent
      extensive elongation. When the contact radius was reduced by approximately 50%,
      the cell then detached quickly from its substrate. The aspiration pressure
      required to detach a Jurkat cell from its substrate was comparable to that
      required to detach a cytotoxic T cell from its target cell. Jurkat cells that had
      been separated from the substrate again adhered strongly to the planar bilayer
      when brought to proximity by micromanipulation. In experiments using the planar
      bilayer containing the TM isoform of LFA-3, Jurkat cells detached with little
      resistance to micromanipulation and without changing their round shape.

PMID- 1370842
TI  - Acquisition of thermotolerance induced by heat and arsenite in HeLa S3 cells:
      multiple pathways to induce tolerance?
AB  - Recent data indicate that cells may acquire thermotolerance via more than one
      route. In this study, we observed differences in thermotolerance development in
      HeLa S3 cells induced by prior heating (15 minutes at 44 degrees C) or
      pretreatment with sodium-arsenite (1 hour at 37 degrees C, 100 microM).
      Inhibition of overall protein and heat shock protein (HSP) synthesis (greater
      than 95%) by cycloheximide (25 micrograms/ml) during tolerance development nearly
      completely abolished thermotolerance induced by arsenite, while significant
      levels of heat-induced thermotolerance were still apparent. The same dependence
      of protein synthesis was found for resistance against sodium-arsenite toxicity.
      Toxic heat, but not toxic arsenite treatments caused heat damage in the cell
      nucleus, measured as an increase in the protein mass of nuclei isolated from
      treated cells (intranuclear protein aggregation). Recovery from this intranuclear
      protein aggregation was observed during post-heat incubations of the cells at 37
      degrees C. The rate of recovery was faster in heat-induced tolerant cells than in
      nontolerant cells. Arsenite-induced tolerant cells did not show an enhanced rate
      of recovery from the heat-induced intranuclear protein aggregation. In parallel,
      hyperthermic inhibition of RNA synthesis was the same in tolerant and nontolerant
      cells, whereas post-heat recovery was enhanced in heat-induced, but not arsenite
      induced thermotolerant cells. The more rapid recovery from heat damage in the
      nucleus (protein aggregation and RNA synthesis) in cells made tolerant by a prior
      heat treatment seemed related to the ability of heat (but not arsenite) to induce
      HSP translocations to the nucleus.

PMID- 1370843
TI  - Mitogenic, melanogenic, and cAMP responses of cultured neonatal human melanocytes
      to commonly used mitogens.
AB  - The following studies have been undertaken to compare and correlate the effects
      of 12-O-tetradecanoylphorbol acetate (TPA), basic fibroblast growth factor
      (bFGF), cholera toxin (CT), and isobutyl methylxanthine (IBMX) on neonatal human
      melanocyte (NHM) proliferation, tyrosinase activity, and cyclic adenosine
      monophosphate (cAMP) concentration. NHM proliferated at a maximal rate in medium
      containing 8 nM TPA, 200 ng/ml CT, and 10(-4) M IBMX. TPA alone did not result in
      optimal melanocyte proliferation, and, as previously shown, its mitogenic effect
      was greatly enhanced by the addition of CT and IBMX individually or
      concomitantly. Human recombinant (hr) bFGF could replace TPA in the NHM growth
      medium. Maximal proliferation was achieved using 3 ng/ml hrbFGF, 20 ng/ml CT, and
      10(-4) M IBMX. The mitogenic effect of 1.2 ng/ml hrbFGF was potentiated in the
      concomitant but not individual presence of CT and IBMX. TPA alone in the absence
      of CT and IBMX caused a dose-dependent stimulation of tyrosinase activity.
      Maximal tyrosinase activity was obtained in the presence of 0.8 nM TPA, 20 ng/ml
      CT, and 10(-4) M IBMX. Unlike TPA, hrbFGF alone resulted in inhibition of
      tyrosinase activity. In the presence of hrbFGF, tyrosinase activity was
      potentiated by CT and IBMX, but not by CT alone. Neither TPA nor hrbFGF alone
      could increase intracellular cAMP levels. The effects of CT and IBMX on
      intracellular cAMP concentration were enhanced to a greater extent by TPA than by
      hrbFGF. Under our experimental conditions, in the presence of hrbFGF, CT but not
      IBMX resulted in a dose-dependent increase in cAMP concentration. Further studies
      on NHM will be aimed at determining the exact role of protein kinase C (PKC) in
      regulating proliferation and melanogenesis and the mechanism(s) activated by
      hrbFGF.

PMID- 1370845
TI  - General primer-mediated polymerase chain reaction for detection of enteroviruses:
      application for diagnostic routine and persistent infections.
AB  - The aim of this study was to determine the applicability of the polymerase chain
      reaction (PCR) for routine diagnostic use and for the detection of persistent
      enteroviral infections. To this end, general primers were selected in the highly
      conserved part of the 5'-noncoding region of the enteroviral genome. They were
      tested on 66 different enterovirus serotypes. A specific fragment was amplified
      from 60 of 66 serotypes. An amplification product was not observed from
      coxsackievirus types A11, A17, and A24 and echovirus types 16, 22, and 23.
      Enteroviral RNA was detected by the PCR in routinely collected throat swabs and
      stool specimens that were found to be positive for enterovirus by isolation in
      tissue culture. Enteroviral RNA was detected in one of five myocardial biopsy
      specimens from patients with dilated cardiomyopathy, implicating virus
      persistence. No amplification product was obtained from eight control samples.
      Our results demonstrate the significance of the PCR for the detection of
      enteroviral RNA and, in particular, for the demonstration of persistent
      enteroviral infections.

PMID- 1370844
TI  - Comparison of antibody reactivity to human immunodeficiency virus type 1 (HIV-1)
      gp160 epitopes in sera from HIV-1-infected individuals from Tanzania and from the
      United States.
AB  - In this study, we compared sera from 159 human immunodeficiency virus type 1 (HIV
      1)-infected individuals from Tanzania and 103 infected individuals from the
      United States for antibodies reactive with 10 HIV-1 gp160 epitopes defined by
      synthetic peptides. Our data indicate that the anti-gp160 antibody fine
      specificity differs between infected individuals from these two geographically
      diverse populations. For example, 50% of the Tanzanian sera contained antibodies
      reactive with an immunodominant HIV-1 gp41 epitope defined by peptide 600-611,
      whereas 91% of the sera from the United States were reactive. Differences in
      serologic reactivity between HIV-1-infected individuals from Tanzania and the
      United States were also observed with gp160 epitopes defined by peptides 503-528
      and 846-860. Included among the peptides examined were four which corresponded to
      the V3 region of gp120. The majority of sera from either country contained
      antibodies reactive with peptide RP142, whose V3 sequence is based upon that of
      HIV-1 isolate MN. Further characterization of serologic reactivity suggested that
      sera from Tanzania were more likely to neutralize HIV-1 isolate IIIB or MN in
      vitro than were sera from the United States. These differences in antibody fine
      specificity between HIV-1-infected individuals from Tanzania and the United
      States suggest that regional isolates of HIV-1 may exist.

PMID- 1370846
TI  - Characterization and classification of strains of Francisella tularensis isolated
      in the central Asian focus of the Soviet Union and in Japan.
AB  - The two subspecies of Francisella tularensis, F. tularensis subsp. tularensis
      (type A) and F. tularensis subsp. palaearctica (type B), differ from each other
      in biochemistry and virulence. Strains of F. tularensis subsp. tularensis are
      believed to be confined to North America, whereas strains of F. tularensis subsp.
      palaearctica occur in Europe, in Asia, and in North America. Moreover, the
      existence of two other subspecies, designated F. tularensis subsp. mediaasiatica
      and F. tularensis subsp. palaearcitica japonica, has been suggested for strains
      of F. tularensis isolated in the central Asian focus of the Soviet Union and in
      Japan, respectively. In the present study, strains biochemically classified as F.
      tularensis subsp. mediaasiatica or F. tularensis subsp. palaearctica japonica
      have been investigated by hybridization with probes specific to 16S rRNAs of the
      two main subspecies. Furthermore, the virulence and biochemical characteristics
      of the strains were compared with those of strains belonging to F. tularensis
      subsp. palaearctica and F. tularensis subsp. tularensis. It was found that 16S
      rRNAs of F. tularensis subsp. mediaasiatica and F. tularensis subsp. palaearctica
      japonica hybridize with the probe specific to a genotype proposed herein,
      genotype A (F. tularensis subsp. tularensis), which shows that strains
      genetically related to this subspecies are found outside North America. However,
      the central Asian strains differed from F. tularensis subsp. palaearctica and F.
      tularensis subsp. tularensis strains when investigated by fermentation of
      glucose. The results of the biochemical tests could not be unambiguously used for
      differentiation of strains into F. tularensis subsp. palaearctica or F.
      tularensis subsp. tularensis. These drawbacks suggest that classification of
      strains of Francisella on the basis of 16S rRNA analysis may be preferable to
      classification on the basis of biochemical analysis.

PMID- 1370847
TI  - Amplification and analysis of specific DNA and RNA sequences of bovine leukemia
      virus from infected cows by polymerase chain reaction.
AB  - Bovine leukemia virus (BLV) is the etiologic agent of leukemia in cattle and is
      believed to cause decreases in milk productivity, fertility, and life span in
      infected cows. BLV is a type C retrovirus in the Oncovirinae subfamily. It is
      most closely related to human T-cell lymphoma/leukemia virus type I (HTLV-I) and
      type II (HTLV-II). Since the polymerase chain reaction (PCR) provides rapid and
      efficient amplification of DNA sequences, primers were designed to amplify
      regions of the polymerase (pol) and pX genes specific for BLV targets. These sets
      of primers consistently amplified as few as 10 copies of BLV DNA contained in a
      plasmid in the background of 1 microgram of either human or bovine chromosomal
      DNA. In addition, no amplification products were detected from cell lines
      infected with HTLV-I, HTLV-II, or human immunodeficiency virus type 1 or 2 by the
      BLV PCR systems. Samples of peripheral blood mononuclear cells from 18 cows,
      previously determined to be serologically positive or negative, were correctly
      identified in a blind study as containing proviral DNA by use of the BLV primers
      and probes. Cloning and sequencing of amplified products revealed finite sequence
      variations among a previously cloned BLV isolate, the wild-type virus, and the
      published genome. Reverse transcriptase-directed PCR with the primers for both
      BLV pol and BLV pX was performed on plasma from a BLV-infected cow and detected
      in vivo BLV RNA expression. In summary, we have developed a specific and
      sensitive assay using PCR for the detection and identification of BLV infections;
      this assay can now be applied to clinical and basic research questions in
      veterinary medicine.

PMID- 1370848
TI  - Serotype distribution of Campylobacter jejuni and Campylobacter coli isolated
      from hospitalized patients with diarrhea in central Australia.
AB  - Campylobacter jejuni and/or Campylobacter coli was cultured from 218 of 1,078
      patients of all age groups admitted to Alice Springs Hospital, Alice Springs,
      central Australia, between July 1988 and June 1989 for treatment of diarrhea. One
      hundred sixty-six Campylobacter colonies from 127 patients were subjected to O
      serotyping by using the Penner typing scheme. All except 29 colonies could be
      serotyped. A total of 46 serotypes were identified, and the predominant serotypes
      were O:8, 17, O:22, O:1,44, and O:19. A large proportion of colonies reacted with
      more than one antiserum, and nine serotypes had antigenic compositions not
      observed previously. Several patients had multiple infections with more than one
      serotype, and some patients were shown for the first time to be infected with up
      to three different serotypes. Repeated reinfections with different serotypes were
      seen in some patients. In some patients, provided it was not due to reinfection
      with the same serotype, long-term excretion of the same serotype was seen, and
      for the first time, one patient showed evidence of excretion of the same serotype
      for up to 73 days.

PMID- 1370849
TI  - Detection of enteroviruses in cell cultures by using in situ transcription.
AB  - In situ transcription (IST) was shown to be useful for the detection of human
      enteroviral RNA in cultured cells. A primer to detect a wide variety of
      enteroviral genomes and a coxsackievirus type B3 genome-specific primer were
      demonstrated to be efficient in IST assays. Transcription times greater than 10
      to 30 min did not significantly improve the acquisition of a specific signal,
      whereas the signal-to-noise ratio decreased with time. Inclusion of actinomycin D
      to suppress DNA-dependent DNA polymerase activity in reverse transcriptase
      decreased the signal that was obtained without improving the signal-to-noise
      ratio. Use of RNase H-free murine leukemia virus reverse transcriptase in the IST
      reaction increased the signal versus that obtained by use of the avian
      myeloblastosis virus enzyme, which contains endogenous RNase H activity.
      Exogenous RNase H added to the transcription reaction ablated the signal.
      Background transcription because of poorly hybridized (mismatched) primers was
      reduced after primer hybridization and prior to the transcription reaction by
      rinsing fixed cells with 3 M tetramethylammonium chloride at temperatures which
      dissociate mismatched primer-template duplexes. The rapid detection time and the
      simplicity of application suggest that IST can be performed with a high
      specificity for the detection of enteroviral genomic sequences in cultured cells
      and may be more useful than in situ hybridization for the detection of
      enteroviral genomes.

PMID- 1370850
TI  - Rapid detection of Helicobacter pylori in gastric biopsy material by polymerase
      chain reaction.
AB  - By using primers based on the sequence of a species-specific antigen of
      Helicobacter pylori (P. O'Toole, S.M. Logan, M. Kostrzynska. T. Wadstrom, and
      T.J. Trust, J. Bacteriol. 173:505-513, 1991), a protocol was established for
      detection of this microorganism in gastric biopsy samples by the polymerase chain
      reaction (PCR). A single primer pair was used to specifically amplify a 298-bp
      sequence in a rapid two-step PCR. The primers exhibited the same specificity in
      PCR as that which we reported for the species-specific gene probe on which they
      were based. The sensitivity of the method was 20 copies of the target sequence,
      or 70 bacterial cells, under the lysis conditions used for patient-derived
      material. When amplification was performed for a saturating number of cycles,
      visual examination of ethidium bromide-stained gels successfully detected all
      samples subsequently judged to be positive by Southern hybridization of the gel
      with a probe specific for the PCR product. The bacterium could be detected in
      gastric biopsy samples from patients with various gastric diseases, including
      samples from which the bacterium could not be cultured. Only 9 of 19 patients who
      tested positive by PCR of gastric biopsy material were positive when a saliva
      sample was analyzed. Protocols for sample handling which minimized the risk of
      contamination while maximizing the sensitivity of the reaction were established.
      The results support a role for PCR in the rapid identification of H. pylori in
      clinical samples.

PMID- 1370852
TI  - PSA becoming important tool in prostate cancer.

PMID- 1370851
TI  - Isolation and characterization of two distinct human rotavirus strains with G6
      specificity.
AB  - Two new human rotavirus (HRV) strains, PA151 and PA169, with subgroup I
      specificity and a long RNA pattern, yet with a serotype G (VP7) specificity
      different from those of any of the six well-established HRV serotypes (G1 to G4,
      G8, and G9), were isolated 3 months apart from two children with acute
      gastroenteritis in Sicily, southern Italy, in the winter season of 1987 and 1988.
      The HRV isolates were adapted to growth in cell cultures and were then
      characterized by neutralization and RNA-RNA (Northern blot) hybridization. Cross
      neutralization studies with type-specific immune sera to RV serotypes 1 to 10
      showed the antigenic relatedness of the two strains with serotype 6 bovine
      strains UK and NCDV. Monoclonal antibodies to VP7 of UK were able to recognize UK
      and NCDV strains as well as both HRV isolates. Cross-hybridization studies showed
      a genetic relatedness of PA151 and PA169 to bovine strains for all genes except
      gene 4. Gene 4 of PA151 appeared to be genetically related to that of AU228 (a
      human strain of subgroup I and with serotype G3 specificity that belongs to a
      feline genogroup), whereas gene 4 of PA169 appeared to be unique, yet it was
      related to gene 4 of two recently reported subgroup I HRV strains, one (PA710)
      with serotype G3 specificity and the other (HAL1271) with serotype G8
      specificity. The new HRV strains must be taken into consideration when deciding
      strategies for the development of an effective RV vaccine.

PMID- 1370853
TI  - Ordering and administration of sedatives and analgesics during the withholding
      and withdrawal of life support from critically ill patients.
AB  - OBJECTIVE: To determine why and how sedatives and analgesics are ordered and
      administered during the withholding and withdrawal of life support from
      critically ill patients. DESIGN: Prospective case series. SETTING: Medical
      surgical intensive care units at a county hospital and a university hospital.
      PATIENTS: Consecutive 1-year sample of 22 patients from whom life support was
      withheld or withdrawn in one intensive care unit at a county hospital and a
      random sample of 22 similar patients in the intensive care unit in the university
      hospital over the same period. MAIN OUTCOME MEASURES: Physicians and nurses were
      interviewed to determine their reasons for ordering and administering drugs, and
      medical records were reviewed to document amounts of drugs ordered and
      administered. RESULTS: Drugs were given to 75% of patients during withholding and
      withdrawal of life support. Patients who did not receive medication were comatose
      and considered incapable of benefiting from sedation and analgesia. The median
      time until death following the initiation of the withholding or withdrawal of
      life support was 3.5 hours in the patients who received drugs and 1.3 hours in
      those patients who did not (P, not significant). Physicians ordered drugs to
      decrease pain in 88% of patients, to decrease anxiety in 85%, to decrease air
      hunger in 76%, to comfort families in 82%, and to hasten death in 39%; in no
      instance was hastening death the only reason cited. The amounts of
      benzodiazepines and opiates averaged 2.2 mg/h of diazepam and 3.3 mg/h of
      morphine sulfate in the 24 hours before withholding and withdrawal of life
      support and 9.8 mg/h and 11.2 mg/h in the 24 hours thereafter (P less than .025
      and P less than .001, respectively). CONCLUSIONS: Large doses of sedatives and
      analgesics were ordered primarily to relieve pain and suffering during the
      withholding and withdrawal of life support, and death was not hastened by drug
      administration.

PMID- 1370854
TI  - 1H NMR study of cortex neurons and cerebellar granule cells on microcarriers and
      their PCA extracts: lactate production under hypoxia.
AB  - Lactate production of 6-day-old cerebral cortex neurons and 7-day-old cerebellar
      granule cells from mouse brain attached to cytodex 3 microcarriers was studied as
      a function of time, under hypoxic conditions using 1H NMR. Perchloric acid
      extracts of both cell types were prepared and 1H NMR spectra showed compounds
      characteristic for these neurons. In particular the granule cell extracts showed
      a large amount of glutamate as expected from biochemical experiments, whereas the
      cortex neurons showed a large amount of 4-aminobutyric acid.

PMID- 1370855
TI  - Children with cancer: special considerations in the discontinuation of life
      sustaining treatment.
AB  - Every year in the United States, over 2,100 children die of progressive cancer,
      or of complications related to the disease or its treatment. Physicians, other
      clinicians, and parents caring for these children are often faced with decisions
      about the continuation or termination of life-sustaining treatment (LST). In
      adults, a consensus has emerged which holds that LST may be ethically
      discontinued if the burdens of continued treatment outweigh its benefits for the
      patient. While this standard is also applicable to LST decisions in pediatric
      oncology, its appropriate use must address several medical and ethical issues
      characteristic of children with cancer. These special considerations, which are
      the subject of this discussion, include the extensive medical experience of
      children with cancer, the nature of modern oncology treatment, the unpredictable
      patterns of response to treatment, the parent and/or physician biases which may
      threaten the child's well-being, the distinction between being incurably ill and
      imminently dying, the need for effective palliative care, and the variable levels
      of cognitive and emotional development which determine a child's capacity for
      participating in an LST decision. Consideration of these factors facilitates a
      consistent approach to these difficult decisions which is both compatible with
      current ethical guidelines and responsive to the particular needs of these
      patients.

PMID- 1370856
TI  - Response to interferon alfa-2b in a patient with systemic mastocytosis.

PMID- 1370857
TI  - Immune responses in the post-polio syndrome.

PMID- 1370858
TI  - Immune responses in the post-polio syndrome.

PMID- 1370859
TI  - Expression of members of the putative olfactory receptor gene family in mammalian
      germ cells.
AB  - A series of genomic and complementary DNA clones encoding new putative members of
      G protein-coupled receptors were isolated using homology cloning and low
      stringency polymerase chain reaction. Among the unidentified receptors ('orphan
      receptors'), a human genomic clone (HGMP07) was characterized by the presence of
      its transcripts in the testis and by its belonging to a large subfamily of genes
      sharing extensive sequence similarities. Sequence comparison demonstrated that
      this gene subfamily is the human counterpart of the putative rat olfactory
      receptors cloned recently. Another 48 members of the family were cloned. Northern
      blotting further demonstrated the presence of olfactory receptor transcripts in
      germ cells. Our finding suggests that a common receptor gene family encodes
      olfactory receptors and sperm cell receptors that could be involved in chemotaxis
      during fertilization.

PMID- 1370860
TI  - Antigenized antibodies.
AB  - A new process, antigenization of antibodies, consisting of the expression of
      oligopeptides in the hypervariable loops of an antibody molecule is described.
      The potential applications of antigenized antibodies are discussed.

PMID- 1370861
TI  - Molecular analysis of the myoadenylate deaminase deficiencies.
AB  - Myoadenylate deaminase (mAMPD) deficiency in a clinically heterogeous metabolic
      myopathy consisting of primary (inherited) and secondary (acquired) forms based
      on a variety of clinical and laboratory findings. To provide a basis for
      delineating the underlying molecular defects in mAMPD deficiency, and as a means
      to test the proposal for multiple forms of the resulting disease, Northern blot
      analyses were performed with RNA isolated from individual patients with
      classified primary and secondary deficiency utilizing human mAMPD cDNA probes
      isolated from adult skeletal muscle libraries. Analysis of nine patients with
      primary mAMPD deficiency indicates normal abundance of mAMPD transcript. No
      immunoreactive mAMPD polypeptide is detected in Western blot analyses of skeletal
      muscle extracts prepared from these patients. Specificity to mAMPD is
      demonstrated by normal creatine kinase (CK) activities and M-creatine kinase (M
      CK) transcript abundance. Similar analyses of four individuals with secondary
      mAMPD deficiency reveal heterogeneity in this subgroup of patients. Whereas two
      of these patients exhibit normal mAMPD transcript abundance, two others
      associated with inflammatory myopathy display reductions in mAMPD and M-CK
      transcript abundance. Examination of tissue sections derived from the same
      biopsies utilized in the isolation of RNA demonstrates the integrity of the
      skeletal muscle in those patients with associated inflammatory myopathy.
      Combined, these data support the proposal for multiple forms of mAMPD deficiency,
      and indicate that the primary condition is most commonly characterized by
      specific point mutations or small deletions/rearrangements in the ampd1 gene,
      whereas some patients with secondary mAMPD deficiency display more generalized
      aberrations in gene expression.

PMID- 1370862
TI  - Brain neurotransmitter changes in human narcolepsy.
AB  - We measured the concentrations of the three major monoamine neurotransmitters
      noradrenaline, dopamine, and serotonin, their metabolites, and receptor binding
      sites in autopsied brain of three patients with narcolepsy. As compared with the
      controls, concentrations of the noradrenaline and serotonin metabolites MHPG and
      5-HIAA, respectively, were markedly elevated in cerebral cortical subdivisions of
      the narcolepsy patients together with a trend for above-normal
      neurotransmitter/metabolite "turnover" ratio. A moderately reduced number of
      alpha 1-adrenoceptors, as judged by the reduced levels of 3H-prazosin binding,
      was observed in cerebral cortex of two of the three patients with narcolepsy.
      Mean striatal levels of dopamine and its metabolite homovanillic acid were
      normal, whereas the concentration of dopamine's second metabolite,
      dihydroxyphenylacetic acid, was markedly reduced by 50% or greater. This was
      accompanied by a marked increase (+125%) in mean 3H-spiperone binding to the D2
      dopamine receptor in both caudate and putamen; in contrast, the levels of 3H-SCH
      23390 binding to the striatal D1 dopamine receptor were in the normal range. Our
      data provide evidence for altered brain monoaminergic neurotransmitter function
      in human narcolepsy.

PMID- 1370863
TI  - Diffusion-weighted magnetic resonance imaging: rapid and quantitative detection
      of focal brain ischemia.
AB  - We examined serial changes of diffusion- (DWI) and T2-weighted (T2WI) magnetic
      resonance images 30 minutes to 3 hours after intraluminal suture occlusion of the
      middle cerebral artery (MCA) in eight rats and after sham occlusion in four. We
      correlated the abnormal areas on DWI and T2WI with postmortem areas of infarction
      determined by 2,3,5-triphenyltetrazolium chloride (TTC), 24 hours after the
      operation. The 30-minute DWI in each MCA-occluded rat demonstrated increased
      signal intensity in the ipsilateral MCA territory, while T2WI showed no changes.
      At 3 hours, the ipsilateral DWI signal intensity increased further and the area
      of abnormality slightly increased. In some animals, the 3-hour T2WI disclosed an
      area of hyperintensity significantly smaller than that seen on the 30-minute DWI.
      TTC staining demonstrated an extensive MCA infarction in all rats with permanent
      MCA occlusion, confirmed by hematoxylin and eosin staining. The percent infarcted
      area of coronal brain sections, as determined by TTC staining, correlated
      significantly with areas on similar DWI sections at both 30 minutes and 3 hours.
      Sham-occluded control animals did not display any changes on DWI, T2WI, or TTC
      staining. The present study suggests that DWI is a very sensitive modality for
      detecting early ischemic brain injury, being highly correlated with post-mortem
      area of infarction, and may be useful to assess pharmacologic intervention.

PMID- 1370864
TI  - A correlative triad of gadolinium-DTPA MRI, EDSS, and CSF-MBP in relapsing
      multiple sclerosis patients treated with high-dose intravenous
      methylprednisolone.
AB  - In a prospective study, we compared the number of gadolinium-DTPA (Gd-DTPA)
      enhancing lesions on MRI with the CSF and clinical findings before and after a
      total of 20 courses of high-dose intravenous methylprednisolone in relapsing
      multiple sclerosis patients. Before treatment, there was a significant
      correlation of Gd-DTPA enhancement (seen on 16 of 20 scans) and CSF myelin basic
      protein (MBP). If enhancement with Gd-DTPA represents inflammation and CSF-MBP
      indicates myelin breakdown, the amount of inflamed tissue should correlate with
      the amount of myelin being damaged. Clinical improvement occurred following 15 of
      20 courses, and decrease of Gd-DTPA enhancement in 12 of 16 scans; the mean CSF
      MBP level was the only CSF variable to return to reference values. There was a
      significant correlative triad of decrease in CSF-MBP, Gd-DTPA enhancement, and
      clinical disability. Thus, the clinical effect of methylprednisolone might be
      accompanied by a reduction of inflammation and myelin breakdown.

PMID- 1370865
TI  - Immunohistochemical study of intralaryngeal ganglia in the cat.
AB  - To study the mechanism of autonomic regulation in the larynx, intralaryngeal
      local ganglia of the cat were investigated using immunohistochemical techniques.
      Small intralaryngeal ganglia were found in the peripheral portions of internal
      branches of the superior laryngeal nerve. Ninety-one percent of the ganglionic
      neurons were immunoreactive (IR) to vasoactive intestinal polypeptide (VIP), and
      10% of the VIP-IR cells were also immunoreactive to enkephalin (ENK) and/or
      substance P (SP). The immunoreactivity of neuronal cell bodies remained unchanged
      even after denervation of the bilateral superior and recurrent laryngeal nerves.
      A dense distribution of calcitonin gene-related peptide (CGRP)-IR nerve fibers
      was found around almost all neuronal cells in the intralaryngeal ganglia. A few
      VIP-IR, ENK-IR, and SP-IR nerve fibers were also observed. Only the CGRP-IR
      fibers disappeared after the denervation experiments. In the laryngeal glands and
      mucosal arterioles, VIP-IR nerve terminals were found that were also
      immunoreactive to ENK and/or SP. However, these immunoreactive nerve endings in
      the glands and arterioles remained after the denervation experiments. The results
      of our study indicate that laryngeal exocrine secretion and blood flow are
      regulated by postganglionic autonomic parasympathetic fibers from intralaryngeal
      ganglia that contain VIP alone or VIP with ENK and/or SP, and that these
      ganglionic neurons may be innervated by CGRP-IR extrinsic nerve fibers.

PMID- 1370866
TI  - Neurodevelopment of preterm infants: neonatal neurosonographic and serum
      bilirubin studies.
AB  - In this study of 249 preterm infants of less than 34 weeks' gestation, the
      relationships between maximal serum total bilirubin concentrations during the
      neonatal period, neonatal cranial ultrasonographic abnormalities, and severe
      neurodevelopmental sequelae are described. The subjects, who were selected on the
      basis of serial cranial ultrasonographic findings, had repeated neurologic and
      developmental examinations during late infancy and early childhood that
      established the presence (n = 45) or absence (n = 204) of spastic forms of
      cerebral palsy. Of the 204 subjects without cerebral palsy, 23 scored abnormally
      low on standardized developmental testing during early childhood. All but seven
      of the subjects with cerebral palsy had grade III/IV intracranial hemorrhage or
      moderate to severe periventricular echogenicity or both, ultrasonographic
      abnormalities that probably reflect a disruption in the blood-brain barrier as
      well as extravasation of blood into brain tissue; however, analysis of the data
      did not suggest that these cranial ultrasonographic abnormalities increased
      either the maximum serum bilirubin concentration during the neonatal period or
      the susceptibility of the subjects to neurologic damage from hyperbilirubinemia.
      Also, there was no evidence to suggest that bilirubinemia in the range studied
      (2.3 to 22.5 mg/100 mL total serum bilirubin) was causally related to cerebral
      palsy, early developmental delay, or the development of periventricular cysts in
      this population of preterm infants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370867
TI  - Cocaine/polydrug use in pregnancy: two-year follow-up.
AB  - The impact of cocaine on pregnancy and neonatal outcome has been well documented
      over the past few years, but little information regarding long-term outcome of
      the passively exposed infants has been available. In the present study, the 2
      year growth and developmental outcome for three groups of infants is presented:
      group 1 infants exposed to cocaine and usually marijuana and/or alcohol (n =
      106), group 2 infants exposed to marijuana and/or alcohol but no cocaine (n =
      45), and group 3 infants exposed to no drugs during pregnancy. All three groups
      were similar in racial and demographic characteristics and received prenatal care
      through a comprehensive drug treatment and follow-up program for addicted
      pregnant women and their infants. The group 1 infants demonstrated significant
      decreases in birth weight, length, and head circumference, but by a year of age
      had caught up in mean length and weight compared with control infants. The group
      2 infants exhibited only decreased head circumference at birth. Head size in the
      two drug-exposed groups remained significantly smaller than in control infants
      through 2 years of age. On the Bayley Scales of Infant Development, mean
      developmental scores of the two groups of drug-exposed infants did not vary
      significantly from the control group, although an increased proportion of group 1
      and 2 infants scored greater than two standard deviations below the standardized
      mean score on both the Mental Developmental Index and the Psychomotor
      Developmental Index compared with the control infants. Cocaine exposure was found
      to be the single best predictor of head circumference.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1370868
TI  - "Crack kids": not broken.

PMID- 1370869
TI  - Lymphocyte activation and regulation of three adhesion molecules with supposed
      function in homing: LECAM-1 (MEL-14 antigen), LPAM-1/2 (alpha 4-integrin) and
      CD44 (Pgp-1).
AB  - Directed migration of lymphocytes from blood into lymph nodes and gut-associated
      lymphatic tissue, also referred to as homing, is subject to change following
      activation. Lymphocyte migration into lymphoid organs in vivo and binding to high
      endothelial venules in vitro is largely suppressed after short-term stimulation
      with phorbol esters. The observed functional alterations were correlated with
      changes in the expression of three putative homing receptors, LECAM-1 (MEL-14
      antigen), LPAM-1/2 (alpha 4-integrin) and the murine CD44 (Pgp-1, H-CAM, Hermes
      antigen equivalent) upon different modes of cellular activation. Expression of
      LECAM-1 (gp90 MEL-14), a lymphocyte adhesion molecule implicated in targeting
      extravasation into lymph nodes, was found to be lost almost completely within
      minutes after protein kinase C activation. LECAM-1 re-expression occurred within
      less than 24 h. Rapid loss of LECAM-1 was also observed after calcium ionophores
      whereas anti-CD3 or concanavalin A elicited a gradual and heterogeneous loss of
      LECAM-1 becoming detectable after several hours only. A number of cytokines
      tested were not able to induce alterations in LECAM-1 expression. In contrast,
      expression of LPAM-1/2 (alpha 4-integrin) and CD44 (Pgp-1, H-CAM), two adhesion
      molecules supposed to direct extravasation into Peyer's patches, remained stable
      for hours after every stimulus tested; CD44 expression gradually increased 24 h
      after mitogenic activation, whereas a small reduction only was observed for the
      expression of the alpha 4-chain under certain conditions. Thus, reduced
      extravasation of lymphocytes into Peyer's patches after activation is not due to
      a decline in the surface density of LPAM-1/2 alpha-chain or CD44 whereas
      alterations in migration into lymph nodes parallel the expression of LECAM-1.

PMID- 1370870
TI  - Mucin production in cervical intra-epithelial neoplasia.
AB  - Fifty sections showing cervical intra-epithelial neoplasia grade III were stained
      with mucicarmine and periodic acid-Schiff reagents to demonstrate mucin
      production. Seven of these showed mucin within the neoplastic cells (14%); these
      cases were considered to be a form of adenosquamous carcinoma in situ and lend
      support to the hypothesis that invasive adenosquamous carcinomas arise from an
      indifferent reserve cell.

PMID- 1370871
TI  - Prevalence and predictors of ventricular premature complexes in survivors of
      acute myocardial infarction. CAMIAT Pilot Study Group. Canadian Amiodarone
      Myocardial Infarction Arrhythmia Trial.

PMID- 1370872
TI  - Immunocytochemical localization of vasoactive intestinal peptide and substance P
      in the colon from normal subjects and patients with inflammatory bowel disease.
AB  - Neuropeptides form a part of the brain-gut axis which may regulate
      gastrointestinal functions, including immune regulation. Various changes in the
      neuropeptides--most important, vasoactive intestinal peptide and substances P
      (VIP and SP)--have been described in inflammatory bowel disease. We employed a
      sensitive immunoperoxidase (avidin-biotin-peroxidase complex) technique, using
      anti-VIP and anti-SP antibodies to localize and compare the distribution of VIP
      and SP in the colon. Colon specimens from 19 normal subjects, eight patients with
      ulcerative colitis (UC), and eight with Crohn's disease (CD) were used. In the
      normal colon, VIP and SP immunoreactivity (IR) were localized in the muscularis
      mucosa, circular muscles, walls of blood vessels, nerve fibers, and some distinct
      cells, probably enterochromaffin cells. SP-IR was also present in the epithelial
      cells, mainly along the basolateral domain. VIP-IR was considerably diminished at
      all locations in patients with UC and CD. However, the SP-IR was increased in UC
      in the colonic epithelial cells along the basolateral areas. The SP-IR was
      intense in patients with CD, in the epithelium, the granulomas, cells lining the
      mucosal fissure, and in the muscle layers. In contrast to normals, SP-IR in
      patients with CD was observed both in the longitudinal and circular muscles. We
      conclude that VIP-IR and SP-IR are distributed widely in the mucosa, submucosa,
      and in the circular muscle in normal colon. VIP-IR is decreased in UC and CD,
      whereas SP-IR is increased in both, but more so in CD.

PMID- 1370873
TI  - Hyalinized hemangioma of the liver.
AB  - We report the case of a 65-yr-old woman with hyalinized hemangioma of the liver
      which, on radiological examination, resembled primary or metastatic carcinoma of
      the liver. She had undergone a partial colectomy for a sigmoid adenocarcinoma,
      followed by the diagnosis of a hepatic tumor with ultrasonic echogram 5 months
      later. The tumor was depicted as a low-density mass on plain computed tomography
      (CT), and an enhancement at the peripheral portion was noted by contrast CT.
      Hepatic angiography disclosed a faint pooling of contrast medium in segment 8. A
      subsementectomy of the liver was performed under the diagnosis of metastatic
      adenocarcinoma or hepatocellular carcinoma. Histologically, the tumor was
      composed of dense collagenous tissues with marked hyalinization and scattered
      sclerotic vessels. Elastic fibers were distributed concentrically around the
      vessels. Totally hyalinized sclerosis of hemangioma is uncommon, and can be
      erroneously diagnosed as carcinoma by radiologic examination. This unusual
      hemangioma is reported, with pertinent literature.

PMID- 1370874
TI  - Dominant negative and loss of function mutations of the c-kit (mast/stem cell
      growth factor receptor) proto-oncogene in human piebaldism.
AB  - Piebaldism is an autosomal dominant disorder of melanocyte development and is
      characterized by congenital white patches of skin and hair from which melanocytes
      are completely absent. A similar disorder of the mouse, "dominant white spotting"
      (W), results from mutations of the c-kit proto-oncogene, which encodes the
      cellular tyrosine kinase receptor for the mast/stem cell growth factor. We have
      identified c-kit gene mutations in three patients with piebaldism. A missense
      substitution (Phe----Leu) at codon 584, within the tyrosine kinase domain, is
      associated with a severe piebald phenotype, whereas two different frameshifts,
      within codons 561 and 642, are both associated with a variable and relatively
      mild piebald phenotype. This is consistent with a possible "dominant negative"
      effect of missense c-kit polypeptides on the function of the dimeric receptor.

PMID- 1370876
TI  - Myxoid change in malignant lymphoma. Pathogenetic considerations.
AB  - Myxoid change is a rare phenomenon in malignant lymphoma, and its pathogenesis is
      not well understood. We present a case of large B-cell lymphoma of the small
      bowel in which myxoid change is confined to one of the regional lymph nodes
      involved by lymphoma. An increase of vimentin-positive mesenchymal cells in the
      myxoid zones compared with the nonmyxoid areas within the lymph node and a
      complete lack of myxoid change in the tumor occurring in other sites of this case
      suggest that the myxoid stroma results from some local factors (most probably
      tissue edema) stimulating proliferation of fibroblasts/myofibroblasts.

PMID- 1370877
TI  - Monoclonal antibody B72.3 immunostaining of breast carcinoma. Patterns of
      staining and relationship to mucin content and GCDFP-15 reactivity.
AB  - Around 80% of breast carcinomas express the tumor-associated glycoprotein-72, as
      demonstrated by positive immunostaining with the monoclonal antibody B72.3. We
      have investigated the pattern of B72.3 immunostaining in 88 breast carcinomas of
      different types, with the use of an immunoperoxidase technique. As tumor
      associated glycoprotein-72 has mucinlike properties and is usually present in
      cells that show apocrine differentiation, we have also compared the results of
      B72.3 immunostaining in these tumors with the staining results for mucin and
      GCDFP-15, which is another antibody that recognizes apocrine differentiation. A
      variable degree of B72.3 immunostaining was seen in 60 cases (68%). The staining
      patterns varied with the histological type and sometimes within the same type. A
      significant relationship was demonstrated between B72.3 positivity and the
      presence of acidic mucin in the tumors, but not with their staining for GCDFP-15.
      The extent, distribution, and pattern of immunostaining for B72.3 varies in
      different types of breast carcinoma; this fact has to be taken into consideration
      if radiolabeled B72.3 monoclonal antibodies are going to be used for therapeutic
      purposes.

PMID- 1370875
TI  - Cystic fibrosis in the Basque country: high frequency of mutation delta F508 in
      patients of Basque origin.
AB  - The Basque population is one of the oldest populations of Europe. It has been
      suggested that the Basques arose from a population established in western Europe
      during the late Paleolithic Age. The Basque language (Euskera) is a supposedly
      pre-Indo-European language that originates from the first settlers of Europe. The
      variable distribution of the major cystic fibrosis (CF) mutation (delta F508
      deletion) in Europe, with higher frequencies of the mutation in northern Europe
      and lower frequencies in southern Europe, has suggested that the delta F508
      mutation was spread by early farmers migrating from the Middle East during the
      Neolithic period. We have studied 45 CF families from the Basque Country, where
      the incidence of CF is approximately 1/4,500. The birthplaces of the parents and
      grandparents have been traced and are distributed according to their origin as
      Basque or Mixed Basque. The frequency of the delta F508 mutation in the
      chromosomes of Basque origin is 87%, compared with 58% in those of Mixed Basque
      origin. The analysis of haplotypes, both with markers closely linked to the CF
      gene and with intragenic markers, suggests that the delta F508 mutation was not
      spread by the Indo-European invasions but was already present in Europe more than
      10,000 years ago, during the Paleolithic period.

PMID- 1370878
TI  - Prostate-specific antigen and prostate-specific acid phosphatase in
      neuroendocrine cells of prostate cancer.
AB  - Prostate-specific antigen is a specific immunohistochemical marker of benign
      prostatic epithelium and prostate cancer. A subpopulation of neuroendocrine cells
      seen in 50% of cancers do not produce this protein marker. These cells appear to
      secrete prostate-specific acid phosphatase. This finding may explain the marked
      variation in serum prostate-specific antigen levels in all stages of prostate
      cancer.

PMID- 1370879
TI  - Hepatic pathology of chronic granulomatous disease of childhood.
AB  - We reviewed the hepatic pathology of seven cases of chronic granulomatous disease
      of childhood. All patients were male, with an age range of 5 to 41 years. Hepatic
      biopsy with drainage or wedge resection was performed in five cases to remove
      abscesses. Autopsy was performed in three cases. Presentation was typical of
      infection (fever, leukocytosis) with an elevated serum alkaline phosphatase
      level. Histologically, the most consistent feature was the presence of foamy
      macrophages that contained a finely granular golden brown pigment, seen in all
      seven cases. These were present as small collections predominantly in the portal
      tracts but were also found in the lobules. Palisading granulomas with central
      necrosis and associated giant cells were seen in four cases, one of which also
      had occasional lobular epithelioid granulomas. One case showed hyalinized portal
      and lobular granulomas. Four cases that showed palisading granulomas cultured
      positive for Staphylococcus aureus. One case cultured Pseudomonas cepacia, and
      one case cultured Streptococcus intermedius. Although palisading granulomas are
      typical of chronic granulomatous disease, they are not seen in all cases. These
      granulomas are similar to granulomas that are seen with Candida and other fungal
      infections and therefore are not specific for chronic granulomatous disease of
      childhood. The pigmented macrophages appear to be a consequence of the primary
      defect of the disease and are not secondary to infection and associated
      inflammation.

PMID- 1370880
TI  - Analysis of the close relationship between human astrocytoma-specific antigens
      detected by murine monoclonal antibodies and c-kit proto-oncogene product.
AB  - Tyrosine-specific phosphorylated proteins found exclusively on the cell surface
      of human astrocytomas were previously identified with murine monoclonal
      antibodies, designated as GA-17, GB-4 and GC-3. The purpose of this study was to
      further characterize the antigens and investigate the relationship between them
      and c-kit protooncogene product. We demonstrated that the antigens had protein
      kinase activity. Moreover, GA-17 reacted with c-kit protein expressed on the
      membrane of A172 human glioblastoma cells.

PMID- 1370881
TI  - Evidence for the expression of growth hormone receptors in human placenta.
AB  - Since human placenta produces a growth hormone variant, it seemed important to
      search for evidence of GH receptors in that organ. Evidence for the expression of
      the GH receptor (GHR) gene was obtained by northern blot analysis. In addition,
      GHR poly A+ RNA was detected in RNA from cultured trophoblastic cells, but not
      from placenta fibroblasts. There was a low but significant specific binding of
      pituitary GH-N and placental GH-V to placenta plasma membranes. Both variants
      apparently bound to the same receptor, which is present in the first trimester as
      well as in the term placenta. These results suggest that placental GH may have
      paracrine or autocrine functions in the placenta.

PMID- 1370882
TI  - Three different NCA species, CGM6/CD67, NCA-95, and NCA-90, are comprised in the
      major 90 to 100-kDa band of granulocyte NCA detectable upon SDS-polyacrylamide
      gel electrophoresis.
AB  - Human granulocytes express several species of nonspecific cross-reacting antigens
      (NCA), glycoproteins belonging to the carcinoembryonic antigen (CEA) family. Our
      previous studies have shown that at least two different NCA of 95 and 90 kDa are
      contained in the major NCA band of 90 to 100 kDa detectable upon gel
      electrophoresis of immunoprecipitates obtained from the cell surfaces of
      granulocytes with polyclonal anti-NCA. In the present study, the 90 to 100-kDa
      NCA band was found to include one more species of 100 kDa. This component was
      reactive with an anti-CD67 antibody as well as polyclonal anti-NCA and released
      from the cell surface with phosphatidylinositol-specific phospholipase C,
      indicating that the 100-kDa NCA species is CD67. Both antibodies revealed high
      binding activities with a recombinant protein of CGM6, which has been identified
      in a leukocyte cDNA library as an NCA gene and found to encode a glycosyl
      phosphatidylinositol-anchored heterotypic cell adhesion molecule. Furthermore,
      the apparent molecular mass of the deglycosylated CD67 (38 kDa) corresponded with
      that of the CGM6 protein. These results suggest that CD67 is equivalent to the
      NCA species CGM6.

PMID- 1370883
TI  - Nucleotide sequence of cDNA for the eclosion hormone of the silkworm, Bombyx
      mori, and the expression in a brain.
AB  - The cDNAs encoding eclosion hormone (EH) of the silkworm, Bombyx mori, were
      isolated and sequenced. The results showed that the pre-EH molecule contains a 26
      amino acid signal peptide and a 62-amino acid mature EH. The deduced amino acid
      sequence agreed with that previously determined by the peptide analysis. The
      presence of leucine residue at the carboxyl terminal of EH, which had not been
      detected directly by the peptide analysis, was proved. Primer extension and
      Northern hybridization analyses revealed that 0.9 kb mRNA is transcribed and it
      has a 66-nucleotide non-translated sequence at the 5'-end region. In situ
      hybridization showed that the EH gene is expressed in two pairs of nuerosecretory
      cells in the brain of 5th instar larva.

PMID- 1370884
TI  - Expression of the signal transducing regions of CD4-like and lck genes in murine
      egg.
AB  - We previously demonstrated that the MHC class II molecule on murine sperm and CD4
      like molecule on the egg vitelline membrane are involved in fertilization. In
      this study, the RNA transcripts in murine eggs corresponding to parts of the CD4
      gene and lck gene in thymocytes were demonstrated by means of the reverse
      transcriptase (RT)/polymerase chain reaction (PCR) followed by the sequencing of
      the PCR products. The deduced sequences potentially encode the amino acid
      sequence of the transmembrane to the cytoplasmic domain of CD4 and that of the N
      terminal domain of p56lck respectively. These findings indicate that a signal
      transducing complex similar to that in immune T cells is expressed at the
      transcriptional level in murine eggs.

PMID- 1370885
TI  - Comparison of the primary structure of the functional domains of human and
      porcine von Willebrand factor that mediate platelet adhesion.
AB  - Porcine von Willebrand factor (vWF) directly aggregates human platelets in vitro
      indicating a conformational difference between the human and porcine molecules.
      We amplified and directly sequenced 1242 nucleotides of porcine vWF cDNA that
      encodes functional domains which mediate the binding of vWF to platelets and
      subendothelium. The deduced amino acid sequence corresponds to residues 473-891
      of the human mature vWF subunit and is 79% homologous with the human protein.
      Significant differences are found in two discontinuous segments thought to be
      involved in the binding of vWF to platelet glycoprotein Ib. Porcine vWF lacks
      four contiguous residues in the first segment and has two positively charged
      arginine residues in the second. Three point mutations associated with human type
      IIB von Willebrand disease in the first segment of a botrocetin binding site are
      at the same position as mismatches between the pig and human. The second segment
      of the botrocetin site is highly conserved while the third segment shows only a
      60% homology.

PMID- 1370886
TI  - A role for IGF-1 in the rescue of CNS neurons following hypoxic-ischemic injury.
AB  - Three days after unilateral hypoxic-ischemic injury in infant rats insulin-like
      growth factor 1 (IGF-1) production by astrocytes was enhanced in the injured
      region. This was associated with increased expression of mRNA for IGF binding
      protein-3 but not for binding protein-1. In adult rats a single lateral
      cerebroventricular injection of IGF-1 two hours following a similar injury
      markedly reduced neuronal loss. It is suggested that endogenous IGF-1 is
      neurotrophic and that centrally administered IGF-1 may have therapeutic potential
      for brain injury.

PMID- 1370888
TI  - The gene encoding vacuolar H(+)-ATPase subunit C is overexpressed in multidrug
      resistant HL60 cells.
AB  - Previous studies have suggested that vacuolar H(+)-ATPase activity may play a
      role in modulating drug transport mechanism in multidrug resistant HL60 cells. In
      the present study we have used a cDNA of human vacuolar H(+)-ATPase subunit C (SC
      H(+)-ATPase) to analyze expression of this gene in HL60 cells isolated for
      resistance to adriamycin or vincristine. The results demonstrate that development
      of resistance to either agent results in a major increase in the levels of SC
      H(+)-ATPase mRNA. Furthermore in resistant cells which have partially reverted to
      drug sensitivity there is a parallel reduction in SC-H(+)-ATPase mRNA levels.
      Southern blot analysis shows that the SC-H(+)-ATPase gene is not amplified in the
      resistant cells. These results therefore demonstrate a correlation between the
      development of multidrug resistance and enhanced expression of the SC-H(+)-ATPase
      gene.

PMID- 1370887
TI  - Regulation of cytochrome P450 IID by acute phase mediators in C3H/HeJ mice.
AB  - Cytochrome P450 IID6 is a drug metabolizing enzyme and the major target antigen
      in LKM-1 antibody positive chronic active hepatitis. The histological hallmark of
      chronic active hepatitis is a lymphocytic infiltrate in the liver. It is unknown
      whether and how cytokines produced and secreted by these tissue infiltrating
      mononuclear cells regulate the cellular expression of cytochrome P450 IID6. To
      study the effect of interleukin 1, tumor necrosis factor and interleukin 6 on the
      hepatocellular RNA expression of cytochrome P450 IID, we injected each of the
      cytokines in C3H/HeJ mice. We found a time-dependent suppression of the
      cytochrome in the liver. Six hours after the intraperitoneal injection of 0.5
      micrograms interleukin 1 beta the specific RNA-expression was reduced to 25% of
      the original level. A similar reduction was found after the injection of 2
      micrograms tumor necrosis factor alpha. A mild suppression to 65% of the original
      level was seen six hours following the dose of 100 ng interleukin 6. Our studies
      show how immune mediators can change the expression of an autoantigen. Further
      studies in the human system are necessary to estimate this regulation for the
      elimination of drugs and in LKM-1 antibody positive chronic active hepatitis.

PMID- 1370889
TI  - Differential susceptibility of phosphatidylcholine small unilamellar vesicles to
      phospholipases A2, C and D in the presence of membrane active peptides.
AB  - Activities of phospholipases C and D along with A2 were followed on egg
      phosphatidylcholine small unilamellar vesicles in the presence of membrane active
      peptides melittin, gramicidin S and alamethicin. Decrease in the activity of
      phospholipase C and D and enhancement of phospholipases A2 activity suggest that
      these enzymes are sensitive to alterations in the lipid packing in the membranes
      in the presence of these peptides. Phospholipase C and D, which have not been
      used to study peptide--membrane interactions, have potential use in studying
      membrane perturbations, since their activities are very sensitive to lipid
      packing.

PMID- 1370890
TI  - Sulfoglycolipids bind to adhesive protein amphoterin (P30) in the nervous system.
AB  - HNK-1 antibody reactive carbohydrate epitope carried by glycolipids and
      glycoproteins has been shown to be involved in cell to cell interactions. It has
      been proposed that the HNK-1 reactive 3-sulfoglucuronyl carbohydrate epitope in
      glycolipids may interact with a cell surface receptor to promote the biological
      response in the developing nervous system. The possible occurrence of such a
      receptor was examined in rat nervous system. A specific binding of
      sulfoglycolipids to a 30 kD protein from adult rat cerebellum is described.
      Little binding was found with neutral glycolipids and gangliosides. The 30 kD
      protein from cerebellum was partially purified on a sulfatide-octyl-Sepharose
      affinity column. Binding of sulfoglucuronyl glycolipids to a similar 30 kD
      protein from forebrain previously identified as amphoterin is also shown.
      Amphoterin is developmentally regulated and is involved in neural cell adhesion
      and neurite extension.

PMID- 1370891
TI  - Different expression of tyrosine aminotransferase and serine deydratase in rat
      livers after partial hepatectomy.
AB  - Tyrosine aminotransferase activity in rat liver increases during the first 24 hrs
      after partial hepatectomy with two peaks, one at 10 hrs and another at 18 hrs.
      This behaviour is due to an increase in TATmRNA synthesis. Expression of serine
      deydratase is also enhanced during the first 5 hrs after hepatectomy. It is
      suggested that the enhanced expression of the two genes is due to an increase in
      hormone incretion particularly glucagon and glucocorticoids.

PMID- 1370893
TI  - Expression of guanylate cyclase-A mRNA in the rat retina: detection using
      polymerase chain reaction.
AB  - A technique based on RNA-PCR was successfully employed for the detection of
      guanylate cyclase-A (GC-A) mRNA in the rat retina. Three sets of primers designed
      from the published cDNA sequence of rat brain guanylate cyclase-A (GC-A) produced
      amplification products of expected sizes from the retina as well as brain.
      Analysis of retinal PCR products yielded a 970 bp sequence, which showed 100%
      homology to the cDNA sequence of GC-A (2343-3312 bp region). Northern blot
      analysis was not very sensitive for the detection of GC-A mRNA in the retina. The
      results indicate that the mRNA for GC-A (or a closely related form) is probably
      expressed in the retina, but at a lower level than that found in the brain.

PMID- 1370892
TI  - Regulation of activin beta A mRNA level by cAMP.
AB  - We demonstrated the presence of five species of the activin beta A mRNA in human
      placenta and one major RNA associated with two minor RNAs of the activin in the
      fetal membrane. We investigated the effect of 8-bromo-cAMP (8-Br-cAMP) on
      accumulation of activin beta A subunit mRNA in human fibrosarcoma HT1080 cells.
      Although low levels of the activin mRNA were detectable in the untreated cells,
      the one main RNA species was predominantly accumulated by 8-Br-cAMP. We propose
      that generation of multiple activin mRNAs in the fetal membrane and cAMP-treated
      HT1080 cells is presumably due to a cell-specific alternative polyadenylation.

PMID- 1370894
TI  - Galanin inhibition of cholecystokinin-8-induced increase in [Ca2+]i in individual
      rat pancreatic B-cells.
AB  - The intracellular free Ca2+ ion concentration [( Ca2+]i) was measured in
      individual rat pancreatic B-cells loaded with fura-2. The cells were prepared by
      enzymatic digestion and fluorescence-activated cell sorting. The resting
      concentration of [Ca2+]i in B-cells was 126.3 +/- 3.1 nM in the presence of 4.4
      mM glucose. Addition of cholecystokinin-8 (CCK-8) resulted in rapid and transient
      rises in [Ca2+]i. Perifusion of B-cells with galanin attenuated the amplitude and
      duration of CCK-8-induced [Ca2+]i changes and this inhibitory effect was
      concentration-dependent and reversible. Perifusion of B-cells with nifedipine, a
      voltage-sensitive Ca2+ channel blocker, reduced the duration of the [Ca2+]i
      increase induced by CCK-8, indicating that the Ca2+ entry from the extracellular
      space was, at least in part, involved in CCK-8-induced increases in [Ca2+]i.

PMID- 1370896
TI  - Ion channels. Ten years of patch-clamp studies.

PMID- 1370895
TI  - Hepatocyte growth factor is a paracrine factor for renal epithelial cells:
      stimulation of DNA synthesis and NA,K-ATPase activity.
AB  - The expressions of mRNAs of hepatocyte growth factor (HGF) and its receptor (c
      met) and its effects were examined in cultured renal epithelial cell lines (OK,
      LLCPK1, and MDCK cells) and rat mesangial cells in primary culture. Northern blot
      analysis revealed the presence of HGF mRNA in mesangial cells, but not in
      epithelial cells. c-met mRNA was detected in epithelial cells, but not in
      mesangial cells. HGF stimulated [3H]-thymidine incorporation (DNA synthesis) dose
      dependently in OK and LLCPK1 cells, but not in MDCK and mesangial cells. Ouabaine
      sensitive rubidium uptake (Na,K-ATPase activity) was stimulated by 63% with HGF
      (10 ng/ml) treatment for 16hr in MDCK cells. The results suggest that HGF is
      produced in the kidney, at least in mesangial cells and works on epithelial cells
      to stimulate the proliferation and/or to modify cell functions in a paracrine
      manner.

PMID- 1370897
TI  - Bovine pancreatic trypsin inhibitor as a probe of large conductance Ca(2+)
      activated K+ channels at an internal site of interaction.
AB  - Bovine pancreatic trypsin inhibitor (BPTI) is a 58 residue protein whose binding
      to various serine proteases has been extensively studied by X-ray
      crystallography. We have found that BPTI also binds to an intracellular site
      associated with the large conductance Ca(2+)-activated K+ channel, as detected by
      the production of subconductance events in single channels incorporated into
      planar lipid bilayers. BPTI is highly homologous to a family of mamba snake
      dendrotoxin proteins that inhibit various K+ channels at an extracellular site.
      BPTI thus provides a useful model system to explore basic mechanisms underlying
      protein-channel interactions.

PMID- 1370898
TI  - Muscarinic regulation of membrane ion channels in airway smooth muscle cells.
AB  - We have demonstrated that stimulation of airway smooth muscle by muscarinic
      agonists results in a coordinated modulation of two membrane ion channel
      proteins. Both channels are modulated in a similar way, although their effects on
      open-channel probability are opposite. The voltage-dependence of channel activity
      is shifted to more positive potentials in the case of KCa, and to more negative
      potentials in the case of the voltage-dependent calcium channels. Similarly, KCa
      channel dwell-time kinetics are shifted to short open lifetimes, whereas the long
      open state is favored for the large-amplitude voltage-dependent calcium channel.
      Although little is known about the molecular coupling of calcium channels,
      muscarinic inhibition of KCa channels is mediated through a pertussis toxin
      sensitive guanine nucleotide binding protein.

PMID- 1370899
TI  - Increase in CD5+ B cells in juvenile rheumatoid arthritis. Relationship to IgM
      rheumatoid factor expression and disease activity.
AB  - OBJECTIVE: To investigate the association between CD5+ B cell expression and IgM
      rheumatoid factor (IgM-RF) in juvenile rheumatoid arthritis (JRA). METHODS: CD5+
      B cell levels analyzed by flow cytometry and IgM-RF expression determined by
      enzyme-linked immunosorbent assay were compared in children with JRA, children
      with other collagen vascular diseases, and healthy controls. RESULTS: Children
      with polyarticular JRA had expanded populations of CD5+ B cells, and expansion of
      CD5+ B cells and IgM-RF both correlated with disease activity. CONCLUSION: The
      results indicate that an expanded CD5+ B cell population leads to IgM-RF
      production in patients with polyarticular JRA, as well as patients with RA.

PMID- 1370900
TI  - Restriction fragment length polymorphism of the vitronectin gene in patients with
      rheumatic diseases.

PMID- 1370901
TI  - Sensitive chemiluminescent detection of digoxigenin-labeled nucleic acids: a fast
      and simple protocol and its applications.
AB  - A fast and simple protocol for the chemiluminescent detection of digoxigenin
      labeled nucleic acids with anti-digoxigenin antibody Fab fragments coupled to
      alkaline phosphatase and 3-(4-methoxyspiro[1,2-dioxetane-3,2'-tricyclo-[3.3.1.1
      (3,7)]decan]-4- yl)phenyl phosphate as substrate is described. The washing and
      blocking procedure was optimized to yield low background even on positively
      charged nylon membranes. The sensitivity of the system is equal or better than
      radioactive methods. Exposure to x-ray or Polaroid film for up to 30 minutes is
      sufficient for the detection of 70 femtograms of homologous DNA. Human single
      copy genes are detected in Southern blots of as low as 0.3 microgram total
      placental DNA. Blots can be reprobed multiple times very easily. The advantages
      of the digoxigenin system are high sensitivity, absence of background and ease of
      reprobing and are illustrated by applications for single-copy gene detection in
      genomic blots of human DNA, Northern hybridizations to rare mRNA, detection of E.
      coli genes on blots of genomic digests after pulse field gel electrophoresis, as
      well as for nonradioactive DNA sequencing blots with digoxigenin-labeled primers.

PMID- 1370902
TI  - Comparative method for detection of RNA-PCR-amplified signals.
AB  - During the development of a micro-method for the quantitative analysis of gene
      expression, we observed that the sensitivity for detection of PCR-amplified
      product was higher when silver staining was used, compared with either ethidium
      bromide staining (as reported previously) or Southern hybridization with 32P
      labeled oligonucleotide probe. This observation may have an important impact on
      the analysis of RNA-PCR-amplified signal for the quantitation of mRNA expression,
      simply by densitometric scanning of silver-stained polyacrylamide gel. We believe
      that this is the first report to show such a comparison, demonstrating the
      greater sensitivity of silver staining compared with either ethidium bromide
      staining or Southern hybridization utilizing an oligonucleotide probe prepared by
      3'-end labeling with 32P-dATP.

PMID- 1370903
TI  - Increasing specificity from the PCR-RACE technique.

PMID- 1370904
TI  - Improved RNA staining in formaldehyde gels.

PMID- 1370905
TI  - Instant vacublotting of DNA and RNA.

PMID- 1370906
TI  - Mechanisms of insulin inhibition of ACTH-stimulated steroid secretion by cultured
      bovine adrenocortical cells.
AB  - Results of previous studies indicated that insulin at levels comparable to those
      in humans during hyperinsulinemia decreased ACTH-stimulated cortisol and
      androstenedione secretion by bovine adrenal fasciculata-reticularis cells in
      primary culture. In the present studies this inhibitory action was examined
      further by comparing the effects of insulin on ACTH-stimulated corticosteroid
      secretion with its effects on 8-(4-chlorophenylthio)-cAMP (cpt-cAMP), forskolin-
      and [5val]angiotensin II (Ang II)-stimulated corticosteroid secretion. Effects on
      corticosteroid secretion were correlated with effects on cAMP accumulation and
      rates of cAMP production. Monolayers were incubated for 24 h in the absence or
      presence of each agonist alone or in combination with insulin. Insulin (1.7 x 10(
      9) or 17.5 x 10(-9) M) caused about a 50% decrease in cortisol and
      androstenedione secretion in response to ACTH (10(-11) or 10(-8) M). Insulin also
      decreased ACTH-stimulated aldosterone secretion by cultured glomerulosa cells.
      Cpt-cAMP (10(-4) or 10(-3) M)-stimulated increases in cortisol and
      androstenedione secretion were inhibited by insulin, but to a lesser extent than
      those in response to ACTH. The inhibition of cpt-cAMP-stimulated steroid
      secretion was not related to increased degradation of the cyclic nucleotide.
      Increases in cortisol and androstenedione secretion caused by a submaximal
      concentration (10(-6) M) of forskolin were decreased 50-70% by insulin. In
      contrast, insulin failed to significantly affect cortisol or androstenedione
      secretion caused by a maximal concentration (10(-5) M) of forskolin. The
      secretory responses to Ang II (10(-8) M) were also unaffected by insulin. The
      effect of insulin to inhibit ACTH-stimulated steroid secretion was accompanied by
      a reduction in cAMP accumulation as well as an apparent inhibition of adenylate
      cyclase activation. These data indicate that the effect of insulin to attenuate
      ACTH-stimulated corticosteroid secretion results from both an inhibition of ACTH
      stimulated adenylate cyclase activity and an antagonism of the intracellular
      actions of cAMP.

PMID- 1370907
TI  - Density distribution and immunological reactivity of tumor cells from peritoneal
      effusions of patients with ovarian neoplasms.
AB  - Ascitic samples from 19 patients with primary ovarian non-mucinous carcinomas,
      three with Krukenberg tumors and eight with noncancerous peritoneal effusions
      were studied by conventional cytology and immunocytochemical staining. Density
      gradient centrifugation was applied to fractionate ascitic fluid cells. The
      enrichment of cell types by this method facilitated their cytomorphological
      characterization and identification of neoplastic cell subpopulations existing in
      peritoneal effusions. Immunophenotypic studies of cells were made using
      monoclonal antibodies (mAbs) against ovarian carcinoma-associated antigens (OC
      125, 10B, 8C) and carcino-embryonic antigen (CEA). Non-specific cross-reacting
      antigen (NCA) was applied as a marker for granulocytes which often accompany
      peritoneal effusions. Our results indicated that immunofluorescence (IF) staining
      contributed to the distinction between the primary and secondary ovarian
      carcinomas. Density gradient centrifugation appeared to be a useful method for
      separation of mesothelial cells.

PMID- 1370908
TI  - The use of sequential fine-needle aspiration biopsy with flow cytometry to
      monitor radiation induced changes in breast carcinoma.
AB  - Thirteen patients with locally advanced or recurrent breast carcinoma were
      monitored during radiation therapy by multiple, sequential, fine-needle
      aspiration biopsies (FNAB) with flow cytometry. The material was analyzed for
      qualitative cytomorphological evidence of radiation effect and for DNA content
      and cell cycle alterations. DNA ploidy was not affected by the radiation therapy,
      although the aneuploid tumors showed an increased frequency of cell cycle
      alterations. The most common change seen was an increase in S-G2M (58%). Other
      changes included a decrease in the proliferative/growth fraction (17%) and no
      significant redistribution of cells (25%). There was a relationship between the
      initial proliferative activity of the tumors and the type of cell cycle change
      which occurred. Flow cytometric analysis was a better predictor of early clinical
      response than was cytomorphological assessment. Sequential FNAB with flow
      cytometry is an effective method of monitoring the response of breast cancer to
      radiation therapy.

PMID- 1370909
TI  - Gramicidin conformational studies with mixed-chain unsaturated phospholipid
      bilayer systems.
AB  - The transition of gramicidin from a nonchannel to a channel form was investigated
      using mixed-chain phosphatidylcholine lipid bilayers. Gramicidin and
      phospholipids were codispersed, after removal of the solvents chloroform/methanol
      or trifluoroethanol which resulted in nonchannel and channel conformations,
      respectively, as confirmed using circular dichroism (CD). The fluorescence
      emission maxima of the nonchannel form were shifted toward shorter wavelengths by
      heating at 60 degrees C (for 0-12 h), which converted it to a channel form, again
      as confirmed by CD. The channel form did not respond to heat treatment. Heat
      treatment also increased the fluorescence anisotropy of the nonchannel gramicidin
      tryptophans. The rate of transition from the nonchannel to channel conformation
      was found to be faster if phosphatidylethanolamine was present in combination
      with phosphatidylcholine compared to phosphatidylcholine alone. Also, gramicidin
      in bilayers of the polyunsaturated 1-palmitoyl-2-docosahexaenoyl
      phosphatidylcholine converted more rapidly compared to 1-palmitoyl-2
      oleoylphosphatidylcholine. Using the fluorescence anisotropy of the membrane
      lipid probe 1,6-diphenyl-1,3,5-hexatriene, it was also shown that the motional
      properties of the surrounding lipid acyl chains differed for the channel and
      nonchannel gramicidin conformations. The possibility that lipids tending to favor
      the hexagonal phase (HII) would enhance the rate of the nonchannel to channel
      transition was supported by 31P NMR which revealed the presence of some HII
      lipids in the channel preparations. The results of this study suggest that
      gramicidin may serve as a useful model for similar conformational transitions in
      other more complex membrane proteins.

PMID- 1370910
TI  - Fidelity of HIV-1 reverse transcriptase copying RNA in vitro.
AB  - The genomic hypervariation of human immunodeficiency virus 1 (HIV-1) could result
      from misincorporations by the viral reverse transcriptase. We developed an assay
      for reverse transcriptase fidelity during RNA-dependent as well as DNA-dependent
      DNA polymerization in vitro. A lacZ alpha RNA fragment transcribed by T3 RNA
      polymerase was used to mimic first-strand reverse transcription. The
      corresponding DNA template was used to examine errors by reverse transcriptase
      during second-strand DNA synthesis. With both templates, the mutations introduced
      by reverse transcriptase were identified by their mutant phenotypes in an M13
      lacZ alpha-complementation assay. We found that the reverse transcriptase from
      human immunodeficiency virus 1 (HIV-1 RT) was less accurate than the reverse
      transcriptase from Moloney murine leukemia virus (MLV RT) or the Klenow fragment
      of Escherichia coli DNA polymerase I (Pol I) on either RNA or DNA templates. The
      frequency of misincorporation by HIV-1 RT was 1 in 6900 nucleotides polymerized
      on the RNA template and 1 in 5900 on the DNA template. The error rates of MLV RT
      and Pol I on the RNA template were less than 1 in 28,000 and 37,000,
      respectively. The most frequent mutations produced by HIV-1 RT copying the RNA
      template were C----T transitions and G----T transversions resulting from
      misincorporation of dAMP.

PMID- 1370911
TI  - Appropriate chemotherapy for palliating advanced cancer.

PMID- 1370913
TI  - Angiogenesis.
AB  - The growth of new blood vessels involves the dissolution of the basement
      membrane, outward migration, and proliferation of endothelial cells to form new
      capillaries. In part, angiogenesis is dependent on peptide growth factors, many
      of which have been isolated and are now synthesized by recombinant DNA
      techniques. In animals, angiogenic factors are found in damaged skeletal muscles,
      tumors, and many other tissues. The infusion of angiogenic factors in animals
      improves wound healing, such as in bone and skin grafts. Topically applied growth
      factors in patients with chronic nonhealing cutaneous wounds results in a
      dramatic acceleration of angiogenesis and epithelialization. In diseases in which
      there is an excess of vascularization (tumors, osteoarthritis, diabetic
      retinopathy), research is directed at the identification and production of
      antiangiogenic agents. Although still highly experimental, the clinical use of
      angiogenic and angiostatic agents could cause as significant a change in medical
      practice as antibiotics.

PMID- 1370912
TI  - Steroid hormone agonists and antagonists in the treatment of cancer.

PMID- 1370914
TI  - The occurrence and management of esophageal fistulas resulting from Hodgkin's
      disease.
AB  - At their radiation therapy (RT) department, the authors saw a young woman with an
      esophageal fistula from Hodgkin's disease that was not responsive to
      chemotherapy; this prompted a review of the literature concerning such patients.
      Twenty-two patients with Hodgkin's disease and esophageal fistula were found to
      have been reported previously. Most patients had active disease at the fistula
      site, and most who were treated with RT or chemotherapy had prompt fistula
      closure. Fistula formation as a complication of RT for Hodgkin's disease was
      found to be an extremely unusual occurrence.

PMID- 1370915
TI  - Four cycles of chemotherapy and regional radiation therapy for clinical early
      stage and intermediate-stage Hodgkin's disease.
AB  - To achieve a high percentage of durable complete remissions (CR) and prolonged
      survivals and reduce toxicity in patients with early-stage and intermediate-stage
      Hodgkin's disease, a randomized trial of four cycles of mechlorethamine,
      vincristine, procarbazine, and prednisone (MOPP) versus four cycles of thiotepa,
      bleomycin, and vinblastine (TBV) combined with regional radiation therapy (RT)
      was conducted. For MOPP and RT, the CR percentage was 98% (60 of 61), and at 5
      years, the percentage of patients in CR was 90%, with freedom from progression of
      89% and overall survival of 91%. For TBV and RT, the CR percentage was 93% (55 of
      59), with a 5-year duration of CR of 83%, freedom from progression of 81%, and
      overall survival of 91% (P greater than 0.15). The median follow-up was 65 months
      (range, 7 to 96 months). For 27 patients with clinical Stage IIIA, the CR
      percentage for MOPP and RT was 75% (12 of 16), with 1 relapse and 4 deaths. For
      TBV and RT, the CR percentage for clinical Stage IIIA was 73% (8 of 11) with 2
      relapses and 2 deaths. Short-term toxicity except for transient leukopenia was
      less for TBV and RT than for MOPP and RT. Good results are achievable with
      combined treatment without excessive toxicity.

PMID- 1370916
TI  - Fine-needle aspiration biopsy of small round blue cell tumors of childhood.
AB  - One hundred twenty-eight palpable and deep-seated fine-needle aspiration biopsies
      (FNAB) were done on pediatric patients at James Whitcomb Riley Hospital for
      Children and Indiana University Hospital between 1985 and 1988. During that 4
      year period, 71 (56%) benign and 49 (38%) malignant diagnoses were made. Only
      eight (6%) of the FNAB were considered inadequate. Thirty-nine (80%) of the
      malignant aspirates were small round blue cell tumors of childhood (SRBCT). The
      SRBCT consisted of 21 (54%) lymphomas, 7 (18%) Ewing's sarcomas, 3 (8.5%)
      neuroblastomas, 3 (8.5%) rhabdomyosarcomas, 2 (5.0%) medulloblastomas, 2 (5.0%)
      Wilms' tumors, 1 (3.0%) retinoblastoma, and 1 (3%) granulocytic sarcoma. Fifteen
      (38%) of the SRBCT aspirates were obtained to render a primary diagnosis and 24
      (62%) documented recurrence. Various combinations of electron microscopy,
      immunocytochemistry, and other special stains were used to confirm the diagnosis
      in 11 (28%) cases. These cases consisted of five lymphomas, two
      rhabdomyosarcomas, two Ewing's sarcomas, one neuroblastoma, and one granulocytic
      sarcoma. The technique of FNAB is a successful diagnostic tool for documenting
      primary and recurrent SRBCT in a pediatric population.

PMID- 1370917
TI  - Xenotransplantation of alpha-fetoprotein-producing gastric cancers into nude
      mice. Characteristics and responses to chemotherapy.
AB  - Three human alpha-fetoprotein (AFP)-producing gastric cancers (AFPGC) were
      xenotransplanted into the lateral abdominal wall of nude mice. Two tumors were
      established and passed over ten generations. These tumors retained their ability
      to secrete AFP and their characteristic hepatoid features microscopically. Serum
      levels of AFP in the mice were elevated as the tumors grew. Through serial
      transplantation, the degree of differentiation was not altered. Neither local
      invasion nor distant metastasis were encountered during the observation periods.
      Both strains had an aneuploid pattern of DNA by flow cytometric examinations. The
      responses of these tumors to five chemotherapeutic agents were investigated using
      various doses. The high AFP-titer strain (AFPGC-2) showed a marked regression or
      suppression of tumor growth after administration of both mitomycin C (MMC) and
      cisplatin (CDDP). The low-titer strain (AFPGC-1) had substantial sensitivity only
      to MMC. The growth of both tumors was not suppressed by 5-fluorouracil,
      doxorubicin, or epirubicin. These findings suggest that the characteristics of
      AFPGC are preserved in the xenograft model of nude mice. In addition, MMC and
      CDDP may be active to some extent against this rare, but highly malignant cancer.

PMID- 1370918
TI  - Treatment of unresectable primary liver cancer with intrahepatic
      fluorodeoxyuridine and mitomycin C through an implantable pump.
AB  - Ten patients with unresectable primary liver cancer, eight of whom had elevated
      serum alpha-fetoprotein levels, were treated with intrahepatic fluorodeoxyuridine
      (FUDR) and mitomycin C administered through an implantable pump. Four patients
      had a partial response, and two had a minor response. The median survival from
      initiation of treatment was 14.5 months (range, 2 to 32 months), with patients
      receiving therapy for a median of 11.2 months. In general, the therapy was well
      tolerated; only one patient had treatment-related biliary sclerosis. In
      conclusion, the combination of intrahepatic FUDR and mitomycin C was an effective
      palliative regimen for unresectable primary liver cancer, even in the presence of
      elevated serum alpha-fetoprotein levels. Further studies are needed to confirm
      these findings and compare this regimen with other methods of treatment for
      hepatocellular carcinoma.

PMID- 1370919
TI  - Differential diagnosis of borderline and invasive serous cystadenocarcinomas of
      the ovary by computerized interactive morphometric analysis of nuclear features.
AB  - Whether borderline serous tumors of the ovary can be differentiated from invasive
      serous cystadenocarcinomas by morphometric analysis of nuclear features of the
      neoplastic epithelium was examined. Multiple descriptors extracted from nuclear
      tracings and intranuclear gray-level analysis of argyrophilic nucleolar organizer
      regions were evaluated in 11 borderline and 18 invasive tumors using computerized
      interactive morphometric analysis. These descriptors included: nuclear area and
      perimeter; number, area, and perimeter of argyrophilic nucleolar organizer
      regions; standard deviations of these findings; and a size distribution of
      nuclear areas in discrete classes. Multivariate statistical analysis showed the
      internal consistency of the two groups in terms of physical descriptors and the
      discriminating value of the parameters of nuclear size and pleomorphism
      (independently of nucleolar organizer region parameters). The results indicated
      that interactive morphometric analysis of nuclear features, combined with
      appropriate statistical methods, could be used to distinguish between these
      tumors.

PMID- 1370920
TI  - Enhancement of chemotherapeutic effects by recombinant human granulocyte colony
      stimulating factor on implanted mouse bladder cancer cells (MBT-2).
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was
      administered intraperitoneally in combination with multidrug chemotherapy using
      methotrexate (M), vinblastine (V), doxorubicin (A), and cisplatin (C, or for the
      combination, MVAC) to C3H/He mice (5-week-old females) after experimental
      carcinoma, MBT-2, a transplantable transitional cell carcinoma of the urinary
      bladder had been implanted. The effects of therapy were studied. The animal
      groups consisted of: (1) control (no drug administration), (2) rhG-CSF (100
      micrograms/kg/d, from days 8 through 42 after MBT-2 implantation, except for the
      days when MVAC was administered), (3) high-dose MVAC (2 mg/kg of M, 0.2 mg/kg of
      V, 2 mg/kg of A, and 4 mg/kg of C once a week for 3 weeks), (4) low-dose MVAC
      (one-quarter of the high dose), (5) high-dose MVAC with rhG-CSF, and (6) low-dose
      MVAC with rhG-CSF. In an in vitro system, rhG-CSF did not show any effect on the
      proliferation of MBT-2 cells or exert any influences on A's tumor proliferation
      suppressing action on MBT-2. However, in an in vivo system, concomitant
      administration of rhG-CSF significantly enhanced the tumor-suppressing effect of
      the MVAC therapy, as did rhG-CSF alone. The greatest effect was observed in the
      group receiving high-dose MVAC plus rhG-CSF. These result suggested that rhG-CSF
      stimulated granulocytes may exert antitumor activity on tumor cells severely
      damaged by chemotherapeutic agents at a relatively high concentration. The
      survival rate was improved to some degree even by administration of rhG-CSF
      alone. Although further study is required to elucidate the action mechanism of
      rhG-CSF, these results suggest that rhG-CSF may be useful clinically to enhance
      the activity of antitumor agents and not only through its ability to alleviate
      granulocytopenia or prevent its development.

PMID- 1370921
TI  - Confocal microscopic and other observations on the distal end of the thick limb
      of the human loop of Henle.
AB  - Various antibodies and lectins were used in a histological study of the human
      renal tubule, particularly of the distal end of the thick limb of the loop of
      Henle. The thick limb, identified by antibody to Tamm-Horsfall protein, ended
      abruptly, either at the macula densa or at a variable distance after it. At this
      point there was an abrupt change in cell size. Confocal microscopy and other
      techniques showed that this point marked an abrupt beginning of tubular staining
      by the cytokeratin antibody PKK2 and the lectin UEA 1, with an abrupt end of
      staining by the lectin DBA. Distal from this point, there were gradual changes in
      staining of the tubule by various reagents including other antibodies to
      cytokeratins. These structural findings suggest that there is a fundamental
      change in the tubule at the end of the thick limb. The abrupt end to the thick
      limb in man resembles that seen in the rat and the rabbit.

PMID- 1370922
TI  - The de novo and salvage pathways for the synthesis of pyrimidine residues of RNA
      predominate in different locations within the mouse duodenal epithelium.
AB  - RNA synthesis was examined by radioautography in mouse duodenal epithelium using
      3H-uridine as a tracer of the salvage pathway and 3H-orotic acid as a tracer of
      the de novo pathway. The incorporation of the two precursors was estimated by
      counting silver grains in light-microscopic and electron-microscopic
      radioautographs at successive levels of crypt and villus. With both precursors,
      silver grains were found over all epithelial nuclei, but in numbers varying by
      location. Thus, after 3H-uridine injection, the number of grains was high over
      nucleolus and nucleoplasm in the base of the crypt, declined gradually in the
      middle and top of the crypt, and was low along the villus. After 3H-orotic acid,
      the number of grains was fairly low throughout, but peaked over the nucleoplasm
      in lower villus cells. The 3H-uridine reaction over nucleolus and nucleoplasm in
      crypt cells was interpreted as synthesis by the salvage pathway of ribosomal RNA
      and heterogeneous RNA, respectively, whereas the 3H-orotic acid reaction over the
      nucleoplasm of some villus cells indicated that these cells synthesized
      heterogeneous RNA by the de novo pathway.

PMID- 1370923
TI  - Effect of spinal microinjections of an antagonist to substance P or somatostatin
      on the exercise pressor reflex.
AB  - The purpose of this study was to determine the heart rate and arterial blood
      pressure changes to isometric skeletal muscle contraction and muscle stretch
      before and after microinjecting an antagonist to substance P (SP) or somatostatin
      (SOM) into the L-7 dorsal horn region of the spinal cord of anesthetized cats.
      Anesthesia was induced by administering an anesthetic gas mixture and was
      subsequently maintained with alpha-chloralose. Triceps surae contraction was
      induced by electrically stimulating the L-7 ventral root. Three muscle
      manipulations (all 1 minute in duration) were performed: 1) continuous tetanic
      contraction, 2) intermittent tetanic contractions (1 second of contraction, 1
      second of relaxation), and 3) passive muscle stretch. Saline microinjections had
      no effect on the cardiovascular responses to these muscle manipulations. However,
      both peptide antagonists blunted the pressor response to a continuous tetanic
      contraction as mean arterial pressure increased 47 +/- 4 and 44 +/- 4 mm Hg
      before and 28 +/- 3 and 28 +/- 4 mm Hg after microinjecting the SP or SOM
      antagonist, respectively. In contrast, neither antagonist influenced the increase
      in mean arterial pressure produced by passive stretch; values were 43 +/- 6
      versus 41 +/- 6 mm Hg (SP antagonist) and 39 +/- 7 versus 42 +/- 7 mm Hg (SOM
      antagonist) before and after injections, respectively. Microinjecting the SOM
      antagonist attenuated the pressor response to intermittent tetanic contractions
      (44 +/- 4 mm Hg before SOM antagonist versus 26 +/- 4 mm Hg after SOM
      antagonist), whereas the SP antagonist had no effect (35 +/- 3 mm Hg before SP
      antagonist versus 32 +/- 4 mm Hg after SP antagonist).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1370924
TI  - Pharmacokinetics of tissue-type plasminogen activator during acute myocardial
      infarction in men. Effect of a prostacyclin analogue.
AB  - BACKGROUND: Coronary reocclusion complicates the thrombolytic therapy of acute
      myocardial infarction despite the routine use of aspirin. This is consistent with
      experimental studies demonstrating that multiple agonists, in addition to
      thromboxane A2, mediate the platelet activation underlying reocclusion.
      Consequently, a more potent antiplatelet therapy with a broader spectrum of
      activity than aspirin may be required in this setting. Prostacyclin and its more
      stable analogue, iloprost, inhibit platelet aggregation to all known agonists and
      exert an additional effect over aspirin alone. Experiments in animal models have
      demonstrated, however, that iloprost increases the clearance of tissue-type
      plasminogen activator (t-PA) and impairs thrombolysis in vivo. This study
      examines whether a similar interaction occurs in humans. METHODS AND RESULTS:
      Twelve patients with acute myocardial infarction received t-PA intravenously, 60
      mg in the first hour and a maintenance infusion of 13.3 mg/hr for 3 hours.
      Patients were assigned in a double-blind fashion to iloprost (2 ng/kg/min) or
      placebo following the initial 90 minutes of the maintenance infusion of t-PA.
      Iloprost decreased mean arterial blood pressure (-10 +/- 2.9 mm Hg, p less than
      0.05) but did not alter heart rate. Steady-state plasma iloprost concentration
      was 591 +/- 64 pmol/l. At this concentration, iloprost markedly inhibited
      platelet aggregation in vitro, particularly in the presence of aspirin. Steady
      state clearance of t-PA was unchanged by iloprost (454 +/- 65 versus 443 +/- 136
      ml/min in controls, p = NS). Furthermore, neither elimination kinetics nor plasma
      protein binding of t-PA was altered by iloprost. CONCLUSIONS: At plasma levels
      that exert a potent antiplatelet effect, iloprost did not alter the
      pharmacokinetics of t-PA in men. Prostacyclin analogues may prove useful as an
      adjunct to plasminogen activators, particularly in patients at high risk for
      thrombotic reocclusion.

PMID- 1370925
TI  - Adrenergic effects on the biology of the adult mammalian cardiocyte.
AB  - BACKGROUND: To delineate the mechanism(s) of catecholamine-mediated cardiac
      toxicity, we exposed cultures of adult cardiac muscle cells, or cardiocytes, to a
      broad range of norepinephrine concentrations. METHODS AND RESULTS: Norepinephrine
      stimulation resulted in a concentration-dependent decrease in cardiocyte
      viability, as demonstrated by a significant decrease in viable rod-shaped cells
      and a significant release of creatine kinase from cells in norepinephrine-treated
      cultures. Norepinephrine-mediated cell toxicity was attenuated significantly by
      beta-adrenoceptor blockade and mimicked by selective stimulation of the beta
      adrenoceptor, whereas the effects mediated by the alpha-adrenoceptor were
      relatively less apparent. When norepinephrine stimulation was examined in terms
      of cardiocyte anabolic activity, there was a concentration-dependent decrease in
      the incorporation of [3H]phenylalanine and [3H]uridine into cytoplasmic protein
      and nuclear RNA, respectively. The decrease in cytoplasmic labeling was largely
      attenuated by beta-adrenoceptor blockade and mimicked by selective stimulation of
      the beta-adrenoceptor, but alpha-adrenoceptor stimulation resulted in relatively
      minor decreases in cytoplasmic labeling. The norepinephrine-induced toxic effect
      appeared to be the result of cyclic AMP-mediated calcium overload of the cell, as
      suggested by studies in which pharmacological strategies that increased
      intracellular cyclic AMP led to decreased cell viability, as well as studies that
      showed that influx of extracellular calcium through the verapamil-sensitive
      calcium channel was necessary for the induction of cell lethality. Additional
      time-course studies showed that norepinephrine caused a rapid, fourfold increase
      in intracellular cyclic AMP, followed by a 3.2-fold increase in intracellular
      calcium [( Ca2+]i). CONCLUSIONS: These results constitute the initial
      demonstration at the cellular level that adrenergic stimulation leads to cyclic
      AMP-mediated calcium overload of the cell, with a resultant decrease in synthetic
      activity and/or viability.

PMID- 1370926
TI  - Substance P-induced granulocyte infiltration in mouse skin: the mast cell
      dependent granulocyte infiltration by the N-terminal peptide is enhanced by the
      activation of vascular endothelial cells by the C-terminal peptide.
AB  - Previous studies have shown that substance P induces granulocyte infiltration in
      mouse skin, which is mediated through mast cell degranulation. However, it is not
      yet known whether the direct effect of substance P on vascular endothelial cells
      is involved in the granulocyte infiltration in the skin. To solve this issue, we
      used the N-terminal peptide substance P1-9 (SP1-9), which is active for mast
      cells but inactive for vascular endothelial cells, and the C-terminal peptide SP6
      11, which is active for vascular endothelial cells but inactive for mast cells,
      since substance P activates both mast cells and vascular endothelial cells. The
      subcutaneous administration of substance P (10(-7)-10(-5)M) caused granulocyte
      (neutrophil and eosinophil) infiltration in the skin of BALB/c mice 6 h after the
      injection. SP1-9 (10(-5)-10(-4) M) also caused granulocyte infiltration of mouse
      skin which was associated with mast cell degranulation. In contrast, SP6-11 (10(
      7)-10(-4) M), which was found to increase the vascular permeability of
      endothelial cells in mouse skin, induced no significant granulocyte infiltration
      nor mast cell degranulation. However, SP6-11 (10(-5)-10(-4) M) enhanced SP1-9
      induced granulocyte infiltration in the skin without any significant increase in
      mast cell degranulation. We conclude that substance P causes granulocyte
      infiltration in mouse skin through both mast cell degranulation induced by the N
      terminal peptide of substance P and the activation of vascular endothelial cells
      induced by the C-terminal peptide of substance P.

PMID- 1370927
TI  - Expression of adhesion molecules in human intestinal graft-versus-host disease.
AB  - The distribution of three cellular adhesion molecules, ICAM-1, ELAM-1 and VCAM-1,
      was studied in normal rectal mucosa and in graft-versus-host disease (GvHD) using
      immunohistological and morphometric techniques. In normal controls, ICAM-1 was
      demonstrable on endothelial cells and leucocytes within the lamina propria, ELAM
      1 on endothelial cells only and VCAM-1 on lamina propria leucocytes, many of
      which exhibited long dendritic processes surrounding the glands. In GvHD, the
      enterocytes became positive for ICAM-1 and this was often associated with the
      presence of intra-epithelial LFA-1+ lymphocytes and macrophages, the latter
      containing debris of apoptotic cells. The staining was, however, restricted to
      the luminal membrane of the epithelial cells, raising doubts about the role of
      ICAM-1 as a ligand for LFA-1 on mucosal leucocytes in rectal GvHD. ELAM-1
      expression was increased in GvHD both in terms of the length of positive
      endothelium and staining intensity. VACM-1 was increased on endothelial cells but
      not leucocytes in the lamina propria in contrast to our previous findings in
      cutaneous GvHD where VCAM-1+ dendritic cells were increased and endothelial cells
      remained negative. Normal patterns of adhesion molecule staining were seen in two
      biopsies exhibiting no morphological evidence of GvHD, from patients who had
      strong clinical evidence of the disease, indicating that immunostaining for these
      molecules is unlikely to be of help in improving the sensitivity of histological
      diagnosis. However, the possibility that adhesion molecule staining may be useful
      in improving diagnostic specificity by helping to distinguish GvHD from identical
      histological changes produced by irradiation and cytotoxic drugs is worthy of
      further investigation.

PMID- 1370928
TI  - Enhancement of the antigen-presenting function of monocytes by cholesterol:
      possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis
      and atherosclerosis.
AB  - Extrinsic allergic alveolitis (EAA) (synonym: hypersensitivity pneumonitis) is a
      hypersensitivity lung disease characterized by lymphocytic infiltrates in the
      pulmonary interstitial tissues. We have previously reported that the numbers of
      lymphocytes in bronchoalveolar lavage (BAL) samples in this disease correlate
      with levels of cholesterol and neutral lipid-laden 'foamy' macrophages. We have
      also reported that the macrophages express an increased density of MHC class II
      antigens (in particular HLA-DQ) which are known to be essential for antigen
      recognition by T lymphocytes. The aim of the present study was to explore whether
      cholesterol is capable of enhancing the antigen-presenting function of
      mononuclear phagocytes by modulating the expression of HLA-D region products.
      Incubation of purified monocytes from healthy volunteers with cholesterol in
      serum-free medium induced a significant increase in both the percentages of
      monocytes expressing HLA-DQ (P less than 0.02) and in the intensity of expression
      of the three HLA-D sub-region products, HLA-DQ, -DP and -DR (P less than 0.02,
      less than 0.01, less than 0.05, respectively). The cholesterol pre-incubated
      monocytes also exhibited enhanced antigen-presenting function (P less than 0.05),
      compared with controls pre-incubated without cholesterol. These findings indicate
      that increases in cholesterol in the extracellular milieu may augment antigen
      presentation by modulating the expression of HLA-D region products on antigen
      presenting cells. Apart from EAA, this observation may also have relevance to
      inflammatory mechanisms in atherosclerosis, where 'foamy' macrophages also occur
      in association with hypercholesterolaemia.

PMID- 1370929
TI  - Concomitant augmentation of CD4+ CD29+ helper inducer and diminution of CD4+
      CD45RA+ suppressor inducer subset in patients infected with human T cell
      lymphotropic virus types I or II.
AB  - To examine the immunomodulatory effects of HTLV infection, lymphocyte subset
      analysis was performed on patients infected with human T cell lymphotropic virus
      type-I (HTLV-I, n = 6) or -II (HTLV-II, n = 12) and on normal blood donors (n =
      16). The percentages of total B lymphocytes (CD19), natural killer (NK) cells
      (CD16), T lymphocytes and their subsets (CD2, CD3, CD4, CD5, CD7, CD8), and IL-2R
      (CD25) were found to be within the range found in normal donors. However, the
      expression of CD8+ HLA-DR+ increased significantly in patients with HTLV-I or
      HTLV-II infection (14.1 +/- 3.9% and 9.7 +/- 2.4% respectively; P less than 0.01)
      when compared with controls (3.2 +/- 1.1%). In addition, there was a
      significantly greater proportion of CD4+CD29+ T lymphocytes (29.3 +/- 6.1% and
      31.1 +/- 9.0%; P less than 0.05) with concomitant diminution of CD4+CD45RA+ T
      lymphocytes (8.3 +/- 3.3% and 11.4 +/- 1.5%; P less than 0.01) in patients
      infected with HTLV-I or HTLV-II respectively, when compared with controls. The
      increased percentage of CD4+CD29+ subpopulations showed a direct correlation (rs
      = 0.86; P less than 0.001) with HTLV-specific antibody production. No difference
      in the CD8 population coexpressing CD29 and S6F1 (an epitope of LFA-1) were
      observed in the HTLV-infected group when compared with normal donors and
      functional analysis exhibited minimal cytotoxicity against lectin labelled
      heterologous target cells. Thus, the shift in the suppressor/cytotoxic to
      helper/inducer 'memory' CD4+ may be associated with immunoregulatory
      abnormalities often found in persons infected with HTLV-I or HTLV-II.

PMID- 1370930
TI  - HBsAg in urine: a new approach for the detection of urinary antigens.
AB  - In order to define the optimal conditions for detection of microbial antigens in
      urine, urinary HBsAg excreted during hepatitis B was chosen as a model. Using
      commercial kits, which mainly involve anti-discontinuous epitopes, we found
      urinary HBsAg in only 50% of patients with HBsAg in their sera. In contrast, with
      an inhibition method involving a monoclonal antibody recognizing a continuous
      epitope, urinary HBsAg was found in 100% of these patients. Structural analysis
      of HBsAg showed that urinary HBsAg is denatured; it can escape detection by
      commercial kits well fitted for detection of native serum HBsAg. General
      implications for the revelation of urinary microbial antigens are discussed.

PMID- 1370931
TI  - Biochemical and functional characterization of the leucocyte tyrosine phosphatase
      CD45 (CD45RO, 180 kD) from human neutrophils. In vivo upregulation of CD45RO
      plasma membrane expression on patients undergoing haemodialysis.
AB  - The biochemical and functional characterization, and the regulation of plasma
      membrane expression of the leucocyte tyrosine phosphatase CD45, have been
      investigated in neutrophils from healthy donors and patients undergoing
      haemodialysis. CD45 proteins of 180 kD and 130-150 kD were precipitated from
      neutrophils from both healthy subjects and haemodialysed patients. Prolonged
      storing, as well as trypsin treatment of samples containing the 180-kD CD45
      protein, generated the 130-150-kD polypeptides. The 130-150-kD CD45 polypeptides
      carried extracellular CD45 epitopes, including the sialic acid-related UCHL1
      epitope (CD45RO). Furthermore, these trypsin-generated CD45 polypeptides did not
      possess phosphatase activity, which could be detected on the 180-kD protein. A
      remarkable quantitative increase of cell surface expression of the neutrophil
      CD45 components was detected both after in vitro neutrophil activation and after
      dialysis treatment with neutropenic membranes. The CD45 biochemical pattern did
      not qualitatively change upon either in vitro or in vivo dialysis-induced
      neutrophil activation. The upregulated expression of CD45 on neutrophils from
      dialysed patients correlated with the neutropenic effect induced by the different
      dialyser membranes. Maximal upregulation of CD45 expression was observed after 15
      min of dialysis with neutropenic membranes, and normal expression levels were
      restored after 1 h. By contrast, increase of CD45 plasma membrane expression
      induced in vitro by treatment of normal neutrophils with the degranulatory agents
      fMLP or Ca2+ ionophore was maintained. These results demonstrate that neutrophil
      cell surface expression of the 180-kD CD45 protein is upregulated during the in
      vivo haemodialysis process, and suggest that a proteolytic activity could
      regulate the enzymatic activity of CD45 by degranulation of its cytoplasmic
      phosphatase domains.

PMID- 1370932
TI  - Long-lasting tolerance of articular cartilage after experimental intraoperative
      radiation in rabbits.
AB  - In experimental intraoperative irradiation, 18 adult rabbits received a single,
      50-Gy dose of x-radiation at a unilateral knee joint, and subsequent changes in
      the articular cartilage were examined over a 15-month period by histology,
      scanning electron microscopy, and autoradiography. Although the subchondral bone
      showed histologically typical findings of osteonecrosis three to nine months
      postirradiation, the articular cartilage revealed no obvious degenerative changes
      during the entire study period. Scanning electron microscopy revealed normal
      collagen architecture in the irradiated cartilage for as long as 15 months
      postirradiation. Autoradiography demonstrated active RNA synthesis by the
      irradiated chondrocytes during the same period. These results indicate that
      articular cartilage tissue tolerates intraoperative radiotherapy without
      sustaining serious degenerative changes, unless possible collapse or contracture
      disturbs its biomechanical integrity. The survival of articular cartilage can be
      advantageous for this type of limb-salvage surgery in the treatment of malignant
      bone tumors around a synovial joint.

PMID- 1370933
TI  - Evidence for a role of free radicals by synthesized scavenger, 2
      octadecylascorbic acid, in cerulein-induced mouse acute pancreatitis.
AB  - To define the role of free radicals and of lipid peroxide involvement during the
      progress of cerulein-induced acute pancreatitis in mice, we evaluated the effect
      of a novel free radical scavenger, 2-octadecylascorbic acid (CV-3611), on
      pancreatic edema formation, and the levels of serum enzymes (amylase, lipase) and
      of lipid peroxide in pancreatic tissue. Mice were divided into three groups:
      control group, intraperitoneal injection of saline only; pancreatitis group,
      cerulein 50 micrograms/kg injected intraperitoneally six times at 1-hr intervals;
      treatment groups, CV-3611 10 mg/kg subcutaneously just after intraperitoneal
      cerulein injection. After the cerulein injection, the degree of pancreatic edema
      formation, serum amylase and lipase levels, and the amount of lipid peroxide in
      pancreatic tissue increased significantly during the observation period of 12 hr.
      Treatment with CV-3611 resulted in significant reduction in pancreatic edema
      formation at 3.5 hr (P less than 0.05) and 9 hr (P less than 0.05), serum amylase
      and lipase levels at 3.5 hr (P less than 0.05) and 12 hr (P less than 0.05), and
      lipid peroxide levels at 3.5 hr (P less than 0.05), 6 hr (P less than 0.05) and
      12 hr (P less than 0.05). These results indicate that a novel free radical
      scavenger, CV-3611, has a strong therapeutic effect during the development of
      acute pancreatitis and suggest that oxygen-derived free radicals play an
      important role in the pathogenesis of acute pancreatitis.

PMID- 1370935
TI  - Isolation and characterization of a novel glycosyl-phosphatidylinositol-anchored
      glycoconjugate expressed by developing neurons.
AB  - In search of new markers for studying thymic and nervous system ontogeny, we
      raised rat monoclonal antibodies against glycosyl-phosphatidylinositol-anchored
      molecules among which larger groupings have been shown to be ectoenzymes and
      adhesion molecules. Two of these monoclonal antibodies (H193-4 and H194-563, IgG)
      were found to recognize glycosyl-phosphatidylinositol-anchored glycoconjugates of
      28-33 kDa (P31) and 50-70 kDa in developing mouse brain and thymus respectively,
      when these tissues were analysed by immunoblot experiments. P31 antigen was found
      to be transiently expressed by neurons in neural primary cultures [Rougon, G.,
      Alterman, L., Dennis, K., Guo, X. J. & Kinnon, K. (1991) Eur. J. Immunol. 21,
      1397-1402]. We show in this report that, in developing mouse brain, a maximal
      expression occurred between embryonic day 17 and post-natal day 5, a period that
      corresponds to the formation of neuronal networks. P31 antigen was immunopurified
      and found to possess the following properties: (a) it was soluble in alkaline
      solvents; (b) it bound to DEAE-cellulose and was eluted by a salt gradient of 0-1
      M NaCl; (c) it was sensitive to endoglycosidase F digestion; (d) it was
      insensitive to heparinase, hyaluronidase, chondroitinase ABC, endo-beta
      galactosidase and sialidase treatment; (e) it was labile to mild acid hydrolysis
      without loss of immunoreactivity; (f) it contained phosphate; (g) it lost its
      immunoreactivity after treatment with phosphatidylinositol phospholipase C and
      treatment. These characteristics combine to suggest that P31 is an anionic
      glycoconjugate sharing similarities with Leishmania donovani lipophosphoglycan
      and with the heat-stable antigen recognized by J11d antibody on murine
      hematopoietic cells. This last hypothesis was further confirmed by the
      observation that oligonucleotide probes derived from the heat-stable antigen
      encoding cDNA detect, in developing brain, a 1.8-kb mRNA species similar in size
      to that reported for the heat-stable antigen mRNA and following the same
      developmental expression as P31 antigen.

PMID- 1370934
TI  - Cerulein-induced acute pancreatitis in the rat. Study of pancreatic secretion and
      plasma VIP and secretin levels.
AB  - A study was made with different doses of cerulein (2, 4, 10 and 20 micrograms/kg)
      administered subcutaneously to rats by four injections at intervals of 1 hr; the
      aim of this work was to study exocrine pancreatic secretion of the rat under
      cerulein-induced acute pancreatitis, analyzing enzyme and hydroelectrolyte
      secretion of pancreatic juice. A further aim was to study the relationship
      between the dose of cerulein and the plasma levels of peptides controlling
      hydroelectrolyte secretion of the pancreas, like secretin and vasoactive
      intestinal peptide (VIP). At the lowest dose schedule, the amounts of total
      protein and enzymes (amylase and trypsin) in pancreatic juice decreased
      significantly, plasma amylase increased, and the pancreas became edematous.
      Higher doses magnified these effects. By contrast, ductular function (flow and
      HCO3-) was well preserved in cerulein-treated rats, and this was probably due to
      the significant increase in plasma levels of immunoreactive secretin whereas VIP
      levels were unchanged. The secretin released by treatment with cerulein is able
      to palliate the lack of flow from acinar origin that is affected in the process
      of acute pancreatitis, being a beneficial response to the cerulein treatment.

PMID- 1370936
TI  - Estrogen induction of alcohol dehydrogenase in the uropygial gland of mallard
      ducks.
AB  - Treatment of mallard ducks with estradiol, or a combination of estradiol and
      thyroxine, has been shown to result in the proliferation of peroxisomes and
      production of diesters of 3-hydroxy fatty acids, the female pheromones, in the
      uropygial gland of male and female mallard ducks. Such a treatment results in the
      induction of a unique set of proteins. A cDNA library enriched in hormone-induced
      transcripts was subjected to differential screening. The nucleotide sequence of
      one of the two unique cDNA clones, DGH1, had high similarity to the Human class I
      alcohol dehydrogenase (ADH) gamma subunit and represented the carboxy-terminus of
      the protein from amino acid 190-374. SDS/PAGE and Western blot analysis of the
      proteins indicated that the level of a 38-kDa protein that cross-reacted with
      antibodies prepared against the chicken ADH was increased 5-7-fold by hormone
      treatment. Assays for ADH activity in the uropygial gland extracts of male
      mallards showed a 5-7-fold induction of the enzyme by hormone treatment. The 1.9
      kb ADH mRNA levels were increased 12-14-fold under these conditions. Of all the
      tissues tested, the uropygial gland had the highest levels of ADH mRNA. Induction
      of ADH by estradiol treatment occurred only in this tissue. Elevated levels of
      ADH were also observed in the glands of male mallards in eclipse, the post
      nuptial condition when the hormonal balance is shifted to higher estrogen levels,
      suggesting that this enzyme is regulated by estrogens in this period. Estradiol
      treatment caused an 80% decrease in the NAD+/NADH ratio in the uropygial gland
      and a twofold increase in the fatty alcohol oxidation rate catalyzed by the gland
      extract. These observations could help explain how increased levels of ADH could
      contribute to the production of the diesters.

PMID- 1370937
TI  - Molecular cloning of the murine substance K and substance P receptor genes.
AB  - The peptides substance K and substance P evoke a variety of biological responses
      via distinct, guanosine-nucleotide-binding-regulatory-protein-coupled receptors.
      We have screened a murine genomic cosmid library using oligonucleotide probes and
      have isolated, cloned and characterized the substance K receptor and the
      substance P receptor genes. The coding portion of the substance K receptor gene
      consists of five exons distributed over 13 kbp. The substance P receptor gene is
      considerably larger than that of substance K (more than 30 kbp), however, the
      boundaries of the four exons that have been characterized in the substance P
      receptor gene correspond exactly to the homologous exons in the substance K
      receptor gene. To verify the identity of the isolated genes, we have cloned the
      corresponding cDNA by means of the polymerase chain reaction and we have
      expressed these cDNA species in Xenopus laevis oocytes. The ligand binding
      characteristics determined in this system pharmacologically confirm the identity
      of the two receptors. The deduced amino acid sequence of the mouse substance K
      receptor is 94% identical to the rat sequence and 85% identical to the bovine and
      human sequences. The mouse substance P receptor amino acid sequence is 99%
      identical to the rat sequence. The cloning of the murine substance K and
      substance P receptor genes should contribute substantially to the generation of
      in vivo models for the detailed analysis of the functional significance of these
      receptors.

PMID- 1370938
TI  - Physarum vitronectin-like protein: an Arg-Gly-Asp-dependent cell-spreading
      protein with a distinct NH2-terminal sequence.
AB  - A 70-kDa protein cross-reacted with anti-bovine vitronectin was isolated from
      slime mold Physarum polycephalum. The NH2-terminal amino acid sequence of the
      protein, referred to as Physarum vitronectin-like protein, did not share any
      homology with those of animal vitronectins. It had cell-spreading activity, which
      was specifically inhibited by an Arg-Gly-Asp (RGD)-containing peptide.

PMID- 1370940
TI  - Positively reinforcing effects of the neurokinin substance P in the basal
      forebrain: mediation by its C-terminal sequence.
AB  - The conditioned corral preference paradigm was used to assess reinforcing effects
      of substance P (SP) and its N- and C-terminal fragments injected unilaterally
      into the region of the nucleus basalis magnocellularis (NBM) in rats. Behavioral
      testing was carried out in a circular open field, consisting of 4 quadrants
      equally preferred by the animals prior to conditioning. A single conditioning
      trial was performed. Rats received one microinjection (0.5 microliter) of SP
      (0.74 pmol), of the N-terminal fragment SP (1-7) and the C-terminal fragment
      analog DiMe-C7 (each at doses of 0.074, 0.74, and 74 pmol), or vehicle (phosphate
      buffered saline; PBS). After injection the rats were placed into the open field
      with the four quadrants being separated by Plexiglas barriers (closed corral).
      During the test for conditioned corral preference, when provided a choice between
      the four quadrants, only those rats injected with SP and the equimolar dose of
      DiMe-C7 (0.74 pmol) spent more time in the treatment corral, indicative of a
      positively reinforcing action. None of the other doses of DiMe-C7 and of SP(1-7)
      influenced the preference behavior. For rats injected with 0.74 pmol SP, SP (1
      7), and DiMe-C7, a behavioral analysis was performed for the 15 min conditioning
      trial. SP and DiMe-C7 reduced rearing and grooming behavior, whereas DiMe-C7 and
      SP(1-7) increased locomotor activity. However, the acute behavioral effects of SP
      and its fragments were not correlated with the subsequent place preference
      behavior during the test trial. The results are discussed in the framework of a
      structure/activity relationship for the positively reinforcing properties of SP
      in the region of the NBM. Furthermore, neuropathological implications of the
      present data are considered, since the homologous nucleus basalis of Meynert in
      man is known to degenerate in Alzheimer's disease, which is characterized
      behaviorally by a progressive deterioration in associative functioning.

PMID- 1370939
TI  - Protein kinase C regulates endothelial cell tube formation on basement membrane
      matrix, Matrigel.
AB  - Human umbilical vein endothelial cells differentiate within 12 h to form
      capillary-like networks of tube structures when the cells are plated on Matrigel,
      a mixture of basement membrane proteins. Nothing is known about the intracellular
      signaling events involved in this differentiation. As a first step to define the
      process, we investigated the possible role of protein kinase C activation by beta
      phorbol 12-myristate 13-acetate (PMA) in regulating the formation of the tube
      structures. In this model, PMA increased tube formation several-fold in a dose
      dependent manner with half-maximum stimulation of tube formation at approximately
      5 nM PMA. In the absence of serum, essentially little or no tubes were formed on
      Matrigel unless PMA was added to the medium. Only active phorbol analogs
      increased tube formation, while the protein kinase C inhibitor, H-7, blocked tube
      formation. The protein kinase C activators and inhibitors were effective only
      when added at or just after plating of the cells and did not affect already
      formed tubes. This study suggests that protein kinase C is involved in the early
      events of in vitro endothelial cell tube formation on Matrigel.

PMID- 1370941
TI  - Identification of insulin-like growth factor binding proteins in human oviduct.
AB  - OBJECTIVE: To determine if human oviduct expresses messenger ribonucleic acids
      (mRNAs) encoding insulin-like growth factor binding proteins (IGFBPs), if
      oviductal epithelium secretes IGFBPs into conditioned medium (CM), and if IGFBP
      secretion is regulated by steroid hormones. DESIGN: Northern blots of RNA,
      isolated from late proliferative phase human fimbria and oviductal isthmus, were
      probed with complementary deoxyribonucleic acids encoding IGFBP-1, IGFBP-2, IGFBP
      3, and IGFBP-4. In addition, oviductal ampullary epithelial cells were cultured
      with and without estrogen and/or progesterone (P), and IGFBPs were examined in CM
      by Western ligand blot analysis and identified using specific antisera. SETTING:
      Tissue was obtained from hysterectomy specimens at Stanford University Hospital,
      a private teaching institution. PATIENTS, PARTICIPANTS: Patients undergoing
      hysterectomy for benign disease. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      Transcripts of IGFBP mRNA and IGFBPs secreted into CM were detected by
      autoradiography of Northern and Western ligand blots, respectively. RESULTS:
      Messenger RNA transcripts encoding IGFBP-2, -3, and -4 were detected, whereas
      IGFBP-1 mRNA was barely detectable in oviductal tissue. In CM, IGFBP-2 and IGFBP
      3 were detected, as was a unique 24-kd IGFBP, although IGFBP-1 was not observed.
      Estrogen and/or P did not regulate the secretion of these IGFBPs by cultured
      oviductal epithelium. CONCLUSIONS: Human oviduct expresses mRNAs encoding IGFBP
      2, IGFBP-3, and IGFBP-4, and in vitro oviductal epithelium secretes IGFBP-2,
      IGFBP-3, and a unique binding protein of 24 kd, which may be the recently
      identified IGFBP-4.

PMID- 1370942
TI  - Effect of sperm-immobilizing antibodies on the acrosome reaction of human
      spermatozoa.
AB  - OBJECTIVE: To study by a triple stain technique the effect of sperm-immobilizing
      antibodies on the acrosome reaction of human spermatozoa. DESIGN: The spermatozoa
      were allowed to swim up and culture in a medium containing 7.5% (vol/vol) serum
      with sperm-immobilizing antibodies or control serum up to 6 hours. Sperm mobility
      was analyzed, and the percentage of live acrosome reacted spermatozoa was
      determined. SETTING: Samples were collected from patients referred to university
      hospital infertility clinics. MATERIALS: Serum samples were drawn from seven
      patients with sperm-immobilizing antibodies. All the sera were heat activated and
      stored at -40 degrees C until use. Semen samples were taken from two healthy
      donors. RESULTS: During culture for 6 hours, the percentage of live sperm showing
      the acrosome reaction increased significantly (P less than 0.01) in the control
      group but not in the sperm-immobilizing antibodies group. However, the inhibitory
      effect of sperm-immobilizing antibodies on the acrosome reaction was reversed
      when sperm was reincubated in medium with control serum (P less than 0.01).
      CONCLUSIONS: Sperm-immobilizing antibodies block fertilization at least in part
      by inhibiting the acrosome reaction of human spermatozoa.

PMID- 1370943
TI  - Incidence of sperm with two fluorescent bodies in men with impaired fertility.
AB  - OBJECTIVE: To determine the two fluorescent body (2FLB) frequency in males with
      impaired fertility. DESIGN: Males of couples were evaluated along with their
      female partners for reproductive function. They were classified as having the
      potential for fertility (control group) or as infertile (test group). This was
      based on the evaluation of both members of the couple. Semen parameters were
      determined and analyzed for differences among diagnostic groups. SETTING: The
      setting was clinical secondary care in both private and institutional practice.
      PATIENTS, PARTICIPANTS: The study population was composed of males of couples who
      were being evaluated for infertility. Classification as to reproductive potential
      and categories of abnormality was based on measurement of semen parameters and
      clinical judgment. INTERVENTIONS: Semen specimens were obtained and analyzed from
      78 control and 93 test subjects. MAIN OUTCOME MEASURES: Semen parameters
      including volume, sperm count, sperm motility, percent morphologically abnormal
      sperm, and percent of quinacrine-stained sperm containing zero, one, or two FLBs
      were determined. RESULTS: The test group was found to have a 2FLB frequency that
      was significantly different from that of the control group. The data were then
      analyzed for significant differences in 2FLB frequencies in subpopulations. When
      subjects from all diagnostic subgroups that included varicocele were compared
      with the controls, the 2FLB frequency was significantly elevated (median percent
      of 2FLB was 1.2 versus 0.7). The 2FLB frequency in the remaining diagnostic
      groups was not elevated. CONCLUSIONS: This is the first report of an elevated
      2FLB frequency associated with a biological abnormality. The cause of the
      elevated 2FLB frequency is not known. However, other anomalies that have been
      identified in varicocele patients have been associated with elevated intrascrotal
      temperatures. There are data available that associates elevated temperature with
      aneuploidy in mouse oocytes.

PMID- 1370944
TI  - Alpha 2-macroglobulin and alpha 2-macroglobulin/proteinase complexes in human
      seminal fluid.
AB  - OBJECTIVE: To determine the broad-spectrum proteinase inhibitor alpha 2
      macroglobulin (alpha 2M) and its functional subforms, i.e., free alpha 2M and
      alpha 2M/proteinase complexes, in human seminal fluid by using specific enzyme
      immunoassay systems. SETTING: The study has been performed in the Andrology
      Department of the Dermatology Clinics and the Laboratory of Immunopathology of
      the Institute of Immunology. PATIENTS, PARTICIPATES: Routine patients attending
      the Andrology Department. INTERVENTIONS: The data have been obtained without
      particular interventions before or after collection of seminal fluid. MAIN
      OUTCOME MEASURES: The aim of the study was to determine whether alpha 2M or alpha
      2M/proteinase complexes are present in human seminal fluid. RESULTS: The
      concentration of total alpha 2M in human seminal fluid ranged from 1 to greater
      than 1,000 ng/mL, and between 56% and 85% of the inhibitor was complexed with
      proteinases. CONCLUSIONS: These findings show that alpha 2M and alpha
      2M/proteinase complexes have to be considered as functionally relevant
      biomolecules in male genital tract secretions.

PMID- 1370945
TI  - Seroprevalence of hepatitis C virus nucleocapsid antibodies in patients with
      cryptogenic chronic liver disease.
AB  - The serological responses to two different hepatitis C virus antigens were
      studied by enzyme-linked immunosorbent assay in a variety of chronic liver
      diseases and in healthy blood donors. The study population comprised 97 cases of
      cryptogenic chronic liver disease (40% with a history suggestive of parenterally
      transmitted non-A, non-B hepatitis and 60% without such a history), 87 cases of
      other well-characterized chronic liver diseases and 96 voluntary blood donors.
      The commercially available C100-3 assay and a new assay utilizing a 22 kD
      recombinant protein (c22) from the nucleocapsid region of the virus were used for
      antibody detection. Overall in the non-A, non-B hepatitis group, 77% were
      positive for anti-c22, 55% were positive for anti-C100-3 and 24% were negative by
      both tests. In the parenterally transmitted chronic liver disease group, 82% were
      positive for anti-C100-3 and 90% were positive for anti-c22 (not significant). In
      the cryptogenic chronic liver disease cases 36% were positive for anti-C100-3 and
      67% were positive for anti-c22 (p less than 0.001). Only in one case (a patient
      with hepatitis B virus infection) was anti-C100-3 detected without concomitant
      anti-c22. None of the voluntary blood donors had detectable hepatitis C virus
      antibodies. The new enzyme-linked immunosorbent assay test for anti-c22 would
      appear to be a more sensitive indicator of chronic hepatitis C virus infection
      than the existing commercial test, suggesting a useful diagnostic role in both
      cases of cryptogenic chronic non-A, non-B hepatitis liver disease and for the
      screening of blood products for prevention of hepatitis after transfusion.

PMID- 1370946
TI  - Antibodies against synthetic oligopeptides deduced from the putative core gene
      for the diagnosis of hepatitis virus infection.
AB  - Immunoassays were developed to detect antibodies against oligopeptides deduced
      from the putative core gene of hepatitis C virus, and their performances were
      compared with that of the commercial immunoassay for antibodies against the
      product of nonstructural regions of hepatitis C virus (anti-C100-3). A 19-mer
      oligopeptide (CP10) and a 36-mer oligopeptide (CP9) were chemically synthesized,
      which represented hydrophilic regions of the product of the hepatitis C virus
      core gene. They were used to capture corresponding antibodies, anti-CP10 and anti
      CP9, by enzyme-linked immunosorbent assay in sera from patients with acute or
      chronic non-A, non-B liver disease and in blood donations. At the onset of acute
      non-A, non-B hepatitis, anti-CP10 was detected in 15 of 20 patients (75%), and
      anti-CP9 was detected in 14 patients (70%). This was more frequent than anti-C100
      3, which was found in only 9 patients (45%). In 186 patients with chronic non-A,
      non-B liver disease, anti-CP9, anti-CP10 or both were detected in 170 patients
      (91%). This was more frequent than anti-C100-3, which was found in 138 patients
      (74%). Blood with anti-CP10 as the single serological marker for hepatitis C
      virus infection transmitted non-A, non-B hepatitis by needlestick exposure. In
      sera from 558 apparently healthy blood donors, anti-CP10 was detected in 55
      donors (9.9%), anti-CP9 was detected in 26 donors (4.7%) and anti-C100-3 was
      detected in 7 donors (1.3%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370947
TI  - Vascular adhesion molecules in acute and chronic liver inflammation.
AB  - Adhesion to and penetration through the sinusoidal vascular endothelium is a
      mandatory step for leukocyte migration and accumulation at sites of liver
      inflammation. This leukocyte trafficking is controlled by interactions between
      adhesion molecules on leukocytes and corresponding ligands on endothelial cells.
      We have analyzed the in situ distribution of two recently described vascular
      adhesion molecules (i.e., endothelial leukocyte adhesion molecule-1 and vascular
      cell adhesion molecule-1) and of the lymphocyte "homing" receptor cluster of
      differentiation antigen-44 in normal and inflamed liver biopsy specimens.
      Endothelial leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1
      were absent from normal liver tissue, but they were strongly expressed on
      sinusoidal lining cells in inflammatory liver disease. Endothelial leukocyte
      adhesion molecule-1 expression predominated diffusely throughout the liver
      parenchyma in acute hepatitis; in contrast, vascular cell adhesion molecule-1 was
      mainly expressed in areas of periportal and intralobular inflammation in chronic
      active and persistent hepatitis. The "homing" receptor cluster of differentiation
      antigen-44 was weakly expressed on scattered mononuclear cells and on sinusoidal
      lining cells in normal liver tissue, but it was strongly up-regulated on
      mononuclear inflammatory cells and sinusoidal lining cells in acute and chronic
      hepatitis. In addition, reactivity for the cluster of differentiation antigen-44
      was found on the membranes of variously sized clusters of hepatocytes in biopsy
      specimens with acute hepatitis. De novo or up-regulated expression of these
      adhesion molecules on sinusoidal lining cells in inflamed liver biopsy specimens
      indicates that these cells actively modulate their phenotype in response to
      environmental factors, thus playing a key role in the recruitment of leukocytes
      in acute and chronic liver inflammation.

PMID- 1370950
TI  - Cardiovascular responses of patients with cardiac disease to talking and exercise
      stress testing.
AB  - The blood pressure (BP), heart rate (HR), and premature ventricular contraction
      responses of patients with cardiac disease during talking were compared with
      those during exercise stress testing (EST). BPs, HR, and heart rhythm were
      recorded in 52 patients with cardiac disease before and during talking about an
      intentionally neutral topic and compared with changes during EST. The systolic
      and diastolic BP and HR increased significantly during talking. Diastolic BP
      increased significantly more during talking than during EST stages 1 and 2. The
      increase in diastolic BP during EST stage 3 did not differ from the increase
      during talking. HR and systolic BP increased more during EST than during talking.
      Nine patients had premature ventricular contractions during both EST and talking,
      two during EST only, and one while talking only. The verbalization protocol
      provides information about changes in diastolic BP that are not seen with EST. It
      also may be of value for evaluating heart rhythm, HR, and systolic BP changes for
      patients whose disabilities preclude EST.

PMID- 1370949
TI  - Characterization of epithelial phenotypes in mortal and immortal human breast
      cells.
AB  - We have previously described the mortal human breast epithelial culture MCF-10M,
      that was derived from fibrocystic breast tissue, was cultivated in medium with
      low calcium content for over 2 years, and spontaneously gave rise to the immortal
      MCF-10 cell line. The emergence of immortalized cells, characterized by growth in
      conventional calcium levels, from mortal cells has proven to be a reproducible
      event. Here we report the establishment of a second immortal line from MCF-10M,
      designated MCF-10-2, and establishment of the MCF-12 immortal line after long
      term cultivation of MCF-12M mortal cells from reduction mammoplasty tissue. DNA
      fingerprinting demonstrated the independent, human origin and lineage of the MCF
      10-2 and MCF-12 cell lines. Both lines require cortisol and EGF for maximal
      growth. The expression in these cultures of in vivo breast epithelial phenotypes
      was analyzed using 2-dimensional gel Western blots and immunoperoxidase staining
      with antibodies to cytokeratins and polymorphic epithelial mucin. MCF-10M and MCF
      12M retain the cytokeratin profile of the luminal cell (7, 8, 18, 19), and also
      express cytokeratin 14, found predominantly in basal cells. The immortal lines
      express a similar profile, except that cytokeratin 19, a component of the fully
      differentiated luminal cell, is not expressed in the more uniform population seen
      in MCF-10 and MCF-12, but is retained in the morphologically mixed, less-selected
      population of MCF-10-2. Epitopes on the polymorphic epithelial mucin, recognized
      by antibodies HMFG 1, HMFG 2 and SM-3, were detected in the mortal cultures and
      in the immortal lines, indicating the occurrence of both normal and abnormal
      mucin processing. MCF-10, MCF-10-2 and MCF-12 cells do not form tumors in nude
      mice, but appear to organize as duct-like structures before regressing in the 5th
      week post injection.

PMID- 1370948
TI  - Structure of the genes encoding the CD19 antigen of human and mouse B
      lymphocytes.
AB  - CD19 is a B lymphocyte cell-surface marker that is expressed early during pre-B
      cell differentiation with expression persisting until terminal differentiation
      into plasma cells. CD19 is a member of the Ig gene superfamily with two
      extracellular Ig-like domains separated by a non-Ig-like domain, and with an
      extensive approximately 240 amino acid cytoplasmic domain. In this study,
      Southern blot analysis revealed that the human and mouse CD19 genes were compact
      single copy genes. Both the human and mouse CD19 genes were isolated and the
      nucleotide sequences flanking each exon were determined. Both genes were composed
      of 15 exons and spanned approximately 8 kilobases (kb) of DNA in human and
      approximately 6 kb in mouse. The positions of exon-intron boundaries were
      identical between human and mouse and correlated with the putative functional
      domains of the CD19 protein. The 200 bp region 5' of the putative translation
      initiation AUG codon was well conserved in sequence between human and mouse and
      contained potential transcription regulatory elements. In addition, the 3'
      untranslated regions (UT) of the CD19 genes following the termination codon were
      conserved in sequence. The high level of conservation of nucleotide sequences
      between species in all exons and 5' and 3' UT suggests that expression of the
      CD19 gene may be regulated in a similar fashion in human and mouse.

PMID- 1370951
TI  - Serological diversity and chemical structures of Campylobacter jejuni low
      molecular-weight lipopolysaccharides.
AB  - Low-Mr lipopolysaccharides (LPS) of Campylobacter jejuni reference strains for
      serotypes O:1, O:4, O:23, and O:36 were examined through the liberation of core
      oligosaccharides by mild acid cleavage of the ketosidic linkage of 3-deoxy-D
      manno-2-octulosonic acid residues to the lipid A moiety. The liberated
      oligosaccharides were examined for chemical structure by compositional analysis
      and methylated linkage analysis in conjunction with fast atom bombardment-mass
      spectrometry of permethylated oligosaccharide derivatives. The results showed (i)
      that the LPS contained short oligosaccharide chains of branched nonrepetitive
      structure, to many of which N-acetylneuraminic acid residues remained attached by
      2----3 linkages to 4-linked D-galactose residues in the core structure; (ii) that
      serotypical differences, which are not readily defined through qualitatively
      similar compositions, are clearly reflected in variations in linkage types and
      sequences of sugar residues in the outer core attached to an inner region of
      invariable structure; but (iii) that the presence or absence of NeuAc residues
      does not appear to be a basis for serotypical differences. The results also
      showed that oligosaccharide chains from LPS of serotypes O:1 and O:4 are
      distinctly different and are distinct again from those of the cross-reacting
      serotypes O:23 and O:36, between whose core oligosaccharide chains no differences
      were found. It is concluded that the structurally variable low-Mr LPS from C.
      jejuni show greater similarities to the lipooligosaccharides from Neisseria spp.
      than to the highly conserved core regions of Salmonella species. Those strains
      (serotypes O:23 and O:36) which also furnish high-Mr LPS are unique among gram
      negative bacteria in possessing both low-Mr molecules of the Neisseria
      lipooligosaccharide type and high-Mr LPS of the Salmonella smooth type.

PMID- 1370952
TI  - The 14,000-molecular-weight antigen of Mycobacterium tuberculosis is related to
      the alpha-crystallin family of low-molecular-weight heat shock proteins.
AB  - Eight monoclonal antibodies (MAbs) directed against the 14,000-molecular-weight
      (14K) antigen of Mycobacterium tuberculosis reacted specifically with
      mycobacteria of the M. tuberculosis complex. The nucleotide sequence of the gene
      encoding the 14K antigen was determined by using recombinant DNA clones isolated
      from lambda gt11 and cosmid libraries of the M. tuberculosis genome. The DNA
      sequence of the 14K protein gene coded for a polypeptide of 144 amino acids with
      a calculated molecular mass of 16,277 Da. The 14K antigen has a marked homology
      with proteins belonging to the alpha-crystallin family of low-molecular-weight
      heat shock proteins, which includes the 18K antigen of M. leprae. The eight MAbs
      recognized at least four distinct epitopes localized within the following three
      regions of the 14K protein: amino acids 10 to 92 (MAbs F67-8 and F67-16), amino
      acids 41 to 92 (F159-1 and F159-11), and amino acids 41 to 144 (F23-41, F24-2,
      F23-49, and TB68).

PMID- 1370953
TI  - Amino acid substitutions in naturally occurring variants of ail result in altered
      invasion activity.
AB  - Yersinia enterocolitica is the causative agent of a variety of gastrointestinal
      syndromes ranging from acute enteritis to mesenteric lymphadenitis. In addition,
      systemic infections resulting in high mortality rates can occur in elderly and
      immunocompromised patients. More than 50 serotypes of Y. enterocolitica have been
      identified, but only a few of them commonly cause disease in otherwise healthy
      hosts. Those serotypes that cause disease have been divided into two groups,
      American and non-American, based on their geographical distributions, biotypes,
      and pathogenicity. We have been studying two genes, inv and ail, from Y.
      enterocolitica that confer in tissue culture assays an invasive phenotype that
      strongly correlates with virulence. Some differences between the American and non
      American serotypes at the ail locus were noted previously and have been
      investigated further in this report. The ail locus was cloned from seven Y.
      enterocolitica strains (seven different serotypes). Although the different clones
      produced similar amounts of Ail, the product of the ail gene from non-American
      serotypes (AilNA) was less able to promote invasion by Escherichia coli than was
      the product of the ail gene from American serotypes (AilA). This difference is
      probably due to one or more of the eight amino acid changes found in the derived
      amino acid sequence for the mature form of AilNA compared with that of AilA.
      Seven of these changes are predicted to be in cell surface domains of the protein
      (a model for the proposed folding of Ail within the outer membrane is presented).
      These results are discussed in relation to the growing family of outer membrane
      proteins, which includes Lom from bacteriophage lambda, PagC from salmonella
      typhimurium, and OmpX from Enterobacter cloacae.

PMID- 1370954
TI  - Membrane-derived oligosaccharides affect porin osmoregulation only in media of
      low ionic strength.
AB  - Gram-negative bacteria grown under conditions of low osmolarity accumulate
      significant amounts of periplasmic glucans, membrane-derived oligosaccharides
      (MDO) in Escherichia coli and cyclic glucans in members of the family
      Rhizobiaceae. It was reported previously (W. Fiedlder and H. Rotering, J. Biol.
      Chem. 263:14684-14689, 1988) that mdoA mutants unable to synthesize MDO show a
      number of altered phenotypes, among them a decreased expression of OmpF and an
      increased expression of OmpC, when grown in a Bacto Peptone medium of low
      osmolarity and low ionic strength. Although we confirm the findings of Fiedler
      and Rotering, we find that the regulation of OmpF and OmpC expression in mdoA
      mutants is normal in cells grown on other low-osmolarity media, eliminating the
      possibility that MDO itself might control porin expression. Our data suggest that
      a certain minimal ionic strength in the periplasm is needed for normal porin
      regulation. In media containing very low levels of salt, this may be contributed
      by anionic MDO.

PMID- 1370955
TI  - Osteofibrous dysplasia of long bones--a reactive process to adamantinomatous
      tissue.
AB  - The most controversial aspect of osteofibrous dysplasia (OFD) is its possible
      histogenetic relationship to adamantinoma of long bone. Evidence is recently
      beginning to accumulate that OFD may be a reactive process to regressive
      adamantinoma. To verify the concept, 13 lesions of OFD were studied again by
      immunohistochemistry for cytokeratins of different molecular masses, as well as
      by conventional stainings. In addition, 2 adamantinomas and 6 fibrous dysplasias
      of the tibia were studied for reference. A small number of spindle- or ovoid
      shaped cells scattered individually in the fibro-osseous stroma showed positive
      reactions for cytokeratins of 55-57 kDa in 2 lesions, and for those of 45-56.5
      kDa in 8 lesions of 13 OFDs, although no definite epithelial island could be
      detected even by immunohistochemistry. Adamantinomas also showed single
      cytokeratin-positive cells dispersed in fibroblastic stroma, in addition to
      epithelial islands positive for cytokeratins of both 55-57 kDa and 45-56.5 kDa.
      All cases of fibrous dysplasia were negative for cytokeratins. During the
      observation, no case of OFDs progressed to classic adamantinoma. The present
      study, demonstrating the existence of an intermediate stage between
      "differentiated adamantinoma" and total elimination of adamantinomatous
      components, gives further support for the concept that OFD is a secondary
      reactive process to adamantinomatous tissue. In practice, the existence of single
      scattered cytokeratin-immunoreactive cells in otherwise typical OFDs may not
      indicate the truly malignant behaviour of classic adamantinoma, unless discrete
      epithelioid cell nests are also found.

PMID- 1370956
TI  - Epitope mapping of monoclonal antibodies to Torpedo acetylcholine receptor gamma
      subunits, which specifically recognize the epsilon subunit of mammalian muscle
      acetylcholine receptor.
AB  - Epitopes for four monoclonal antibodies (mAbs) to the gamma subunit of Torpedo
      nicotinic acetylcholine receptor (AChR), and one mAb crossreactive with the gamma
      and delta subunits of Torpedo AChR were mapped using overlapping synthetic
      peptides corresponding to the complete amino acid sequence of Torpedo gamma
      subunit. The epitopes for all mAbs were within a 50 residue sequence region, on
      the cytoplasmic surface of the AChR. Three mAbs crossreacted with mammalian
      muscle AChRs. Two of them specifically recognized the epsilon subunit of AChRs at
      adult neuromuscular junction. The epsilon-specific mAbs were used, in conjunction
      with mAbs specific for the alpha and beta subunits and anti-peptide antisera
      specific for the epsilon, gamma and delta subunits, to identify in Western blots
      the subunit complement of embryonic and adult bovine muscle AChRs.

PMID- 1370957
TI  - DNA sequence analysis and comparison of the variable heavy and light chain
      regions of two IgM, monoclonal, anti-myelin associated glycoprotein antibodies.
AB  - The complete variable heavy and light chain gene sequences of two monoclonal,
      IgM, anti-myelin associated glycoprotein (MAG) antibodies associated with
      peripheral neuropathy, are presented. Comparative analysis of the two VH regions
      has revealed that they are 88% homologous to one another and are both members of
      the VH3 gene family. They are also highly homologous to a gene which is
      frequently utilized in the fetal B-cell repertoire. The V kappa light chain gene
      of one of the antibodies is 99% homologous to a V kappa II gene and the V lambda
      light chain gene of the other antibody is only 72% homologous to other known V
      lambda genes. Further analysis of V genes utilized by anti-MAG antibodies should
      reveal the structural basis for their binding activity.

PMID- 1370958
TI  - Tenascin expression in human glioma cell lines and normal tissues.
AB  - Tenascin expression was evaluated in 21 human glioma cell lines and in normal
      adult tissue extracts by Western and Northern blotting. The cell lines differed
      in their relative expression of tenascin in the cell-associated and supernatant
      compartments. Glioma cell line tenascin production was not uniformly stimulated
      by changes in fetal bovine serum concentration in the growth media. In most
      glioma cell lines and normal tissue extracts, reducing Western blots and Northern
      blots revealed two tenascin species, respectively: a major 340 kDa polypeptide
      and a 9 kb RNA transcript accompanied by a less intense 250 kDa polypeptide and 7
      kDa RNA species. In U-87 MG and in normal adult kidney extracts, however, the 250
      kDa band and 7 kb transcript were more prominent. Quantitation of tenascin in the
      glioma lines revealed variable levels that were significantly higher than those
      in the tissue extracts.

PMID- 1370959
TI  - Production and characterisation of monoclonal antibodies to the mid-region 37-67
      sequence of parathyroid hormone-related protein.
AB  - The production and characterisation of monoclonal antibodies (MAb) to the mid
      region sequence 37-67 of human parathyroid hormone-related protein (PTHRP) is
      described. In spite of the poor immunogenicity of this sub-fragment of PTHRP, a
      high percentage of specific hybrids were produced by boosting with conjugate and
      free peptide prior to cell fusion. Seven of the MAbs produced cross-reacted with
      PTHRP37-67, PTHRP1-86 and native forms of PTHRP. Inhibition studies with peptide
      sub-fragments of PTHRP37-67 indicated that the majority recognised the 45-59
      region. In a RIA for PTHRP1-86, detection limits ranged from 0.17 to 0.9 ng
      PTHRP1-86/tube, and no cross-reaction was found with PTH1-84. Two MAbs 1D11 and
      4B10 were shown to be of potential use in measuring PTHRP1-86 in a two-site
      immunoradiometric assay in combination with either a solid phase consisting of a
      MAb to PTHRP1-34, or iodinated affinity purified rabbit antibodies to PTHRP1-34.
      MAb 1D11 coupled to Sepharose was suitable for immunoextraction of PTHRP, and
      successfully localised PTHRP on immunoblots. Two additional MAbs were produced
      which recognised an epitope unique to PTHRP37-67 located in the 37-46 region of
      the peptide.

PMID- 1370960
TI  - Analysis of amplified T cell receptor V beta transcripts by a non-isotopic
      immunoassay.
AB  - We have recently described a new colorimetric DNA enzyme immunoassay (DEIA) for
      detecting specific hybrids of complementary nucleic acids. This technology is
      based on an antibody that selectively recognizes double, but not single stranded
      DNA and therefore reveals the hybridization event independently from the DNA
      sequences. Most importantly, the test has an ELISA format and is very rapid and
      convenient for processing large numbers of samples. In the present report we have
      adapted this method to reveal the specificity of amplified T cell receptor V beta
      transcripts. V beta genes were amplified by polymerase chain reaction, using
      family specific primers and the specificity of the amplified products was
      determined by Southern blot and by DEIA. Our data demonstrate that DEIA had the
      same degree of sensitivity and specificity of conventional Southern
      hybridization. The possibility of analyzing amplified products with the
      simplicity of a conventional immunoassay should greatly facilitate the analysis
      of complex multigenic systems such as the T cell receptor and the immunoglobulin
      repertoire.

PMID- 1370961
TI  - Atrial parasystolic trigeminy with sinus node echoes during wandering sinus node
      pacemaker in a patient with malignant lymphoma and hypertrophic cardiomyopathy.
AB  - A case of atrial parasystolic trigeminy associated with shifting or wandering
      pacemaker in a patient with malignant lymphoma and hypertrophic cardiomyopathy is
      presented, in which concomitant unsustained sinus node echoes during flattening
      of sinus P wave were observed. This is the first report to prove that wandering
      sinus pacemaker was one of the causes of sinus echoes.

PMID- 1370962
TI  - Pancreatitis in pediatric human immunodeficiency virus infection.
AB  - Because pancreatitis has been reported frequently in adults with human
      immunodeficiency virus infection, we sought to determine the incidence of
      pancreatitis in children with acquired immunodeficiency syndrome by reviewing all
      records of children with AIDS, their serum amylase and lipase levels, and the
      factors associated with pancreatitis through a case-control analysis. During a 6
      year period pancreatitis developed in 9 (17%) of 53 pediatric patients with AIDS.
      Six children had vertical transmission of infection and three patients had
      acquired HIV infection through contaminated blood products. Pancreatitis
      developed at a median age of 5.2 years (range 1.2 to 20 years). All patients had
      vomiting and abdominal pain. When the patients were first seen, lipase values
      were elevated more than amylase values (p = 0.028). Amylase and lipase levels
      declined at comparable rates. In the case-control analysis, pentamidine
      isethionate was significantly associated with pancreatitis (p = 0.02); the risk
      was greater in patients who received pentamidine isethionate and had absolute CD4
      T-lymphocyte counts less than 100 cells/mm3 (p = 0.001). Infections associated
      with the onset of pancreatitis included cytomegalovirus (4), Cryptosporidium (1),
      Pneumocystis carinii pneumonia (3), and Mycobacterium avium intracellulare (1).
      Coinfection with cytomegalovirus was associated with a protracted course in four
      children. Ultrasonographic examination demonstrated biliary ductal dilatation 6
      months after the onset of pancreatitis in one child. Seven children have died at
      a mean of 8 months after the initial onset of pancreatitis; the one living child
      has survived 5 months from the onset of pancreatitis. We conclude that
      pancreatitis is common in pediatric patients with AIDS and may be related to
      pentamidine isethionate exposure, especially when absolute CD4 T-lymphocyte
      counts are less than 100 cells/mm3. Serum amylase levels do not always accurately
      predict the onset of pancreatitis; serum lipase levels should be measured in
      children with symptoms. The onset of pancreatitis in an HIV-infected child is a
      poor prognostic indicator.

PMID- 1370963
TI  - Problems of comorbidity in mortality after prostatectomy.
AB  - OBJECTIVE: In recent studies of patients with benign prostatic hyperplasia (BPH),
      men undergoing transurethral resection of the prostate (TURP) had higher long
      term mortality than men undergoing open prostatectomy. We tested the hypothesis
      that the higher mortality for patients undergoing TURP could have occurred if
      these patients were older and sicker at the time of surgery than patients
      undergoing open prostatectomy. DESIGN AND SETTING: Retrospective cohort study at
      Yale-New Haven (Conn) Hospital. PATIENTS: Two hundred fifty-two men who underwent
      TURP or open prostatectomy from 1979 through 1981 for the treatment of BPH. MAIN
      OUTCOME MEASURES: Five-year mortality adjusted for age and severity of comorbid
      illness at the time of surgery. RESULTS: The crude 5-year mortality rates were
      17.5% (22 of 126 patients) for the TURP group and 13.5% (17 of 126 patients) for
      the open group. At the time of surgery, however, patients in the TURP group were
      sicker and older than patients in the open group. As the detail and quality of
      the assessment of comorbidity increased, the adjusted risk of TURP decreased.
      Improved classifications of comorbidity in three different forms of statistical
      analysis did not show an effect of type of prostatectomy on long-term mortality
      (Mantel-Haenszel relative risk, 1.03; 95% confidence interval, 0.57 to 1.87).
      CONCLUSIONS: These results suggest that TURP does not increase long-term
      mortality after surgery for the treatment of BPH. Inadequate accounting for
      severity of illness may also affect other statistical "adjustments" used in
      research concerned with patient outcomes.

PMID- 1370964
TI  - Diagnostic and therapeutic technology assessment. Endoscopic balloon dilation of
      the prostate.

PMID- 1370965
TI  - Studies on the Thomsen-Friedenreich antigen in human colon with the lectin
      Amaranthin. Normal and neoplastic epithelium express only cryptic T antigen.
AB  - The lectin Amaranthin has been shown to be highly specific for the galactose beta
      1,3 N-acetylgalactosamine-alpha and sialic acid alpha 2,3 galactose beta 1,3 N
      acetylgalactosamine-alpha sequence which represents the Thomsen-Friedenreich (T)
      antigen and its cryptic form, respectively. Previously, we demonstrated the
      usefulness of gold-labeled Amaranthin for the histochemical detection of the T
      antigen and its cryptic form. Application of the galactose oxidase (GO)-Schiff
      sequence abolished lectin binding to the T antigen but not its cryptic form, and
      therefore permitted their differentiation. In the present study we have analyzed
      by light and electron microscopy the distribution and subcellular localization of
      Amaranthin binding sites in normal, dysplastic and neoplastic colonic epithelium.
      Furthermore, a monoclonal antibody raised against synthetic galactose bera 1,3 N
      acetylgalactosamine-alpha-bovine serum albumin was applied as a reagent for the T
      antigen. In normal colonic mucosa, two different Amaranthin staining patterns
      existed: (a) reactivity restricted to the lower portion of the crypts which was
      principally observed in the left colon, and (b) reactivity along the entire
      length of the crypts and in the surface epithelium with goblet cell staining in
      the upper portion of the crypts which was principally observed in the right
      colon. This Amaranthin staining was resistant to GO-Schiff treatment. No
      immunostaining with the monoclonal anti-T antigen was observed. Investigation of
      transitional mucosa, adenocarcinomas of different degrees of differentiation and
      mucinous carcinomas as well as adenomas with different degrees of dysplasia all
      revealed positive Amaranthin staining. The lectin staining was resistant to GO
      Schiff treatment, and immunolabeling with the monoclonal antibody against the T
      antigen was absent. These results indicate that only the cryptic form of the T
      antigen is expressed in normal, dysplastic and neoplastic human colonic
      epithelium.

PMID- 1370966
TI  - Common epitopes of human and murine Mallory bodies and Lewy bodies as revealed by
      a neurofilament antibody.
AB  - The antibody SMI 31, which is directed against a phosphorylated epitope,
      associated with neurofilaments and recognizes Lewy bodies in brains of patients
      with Parkinson's disease (Bancher C, Lassmann H, Budka H, Jellinger K, Grundgke
      Iqbal I, Iqbal K, Wiche G, Seitelberger F, Wisniewski H: J Neuropathol Exp Neurol
      1:81, 1989), decorated in immunofluorescence microscopy Mallory bodies (MBs)
      present in livers of mice chronically treated with griseofulvin and 3,5
      diethoxycarbonyl-1,4-dihydrocollidine. In immunoblots it recognized very acidic
      MB components in a molecular weight range between 55 and 69.5 kilodaltons in
      addition to poorly soluble high molecular weight material. Moreover, an antibody
      to tau protein showed similar reactivities in immunofluorescence microscopy and
      immunoblotting experiments. Both antibodies also stained MBs in human liver with
      alcoholic hepatitis. These observations support and extend earlier findings which
      indicate that several intermediate filament-related cellular inclusion bodies,
      including MBs, share a variety of morphologic, structural and antigenic features.
      They also suggest the involvement of tau or tau-like proteins in MB formation.

PMID- 1370967
TI  - Detection of interleukin-6 and alpha 2-macroglobulin immunoreactivity in cortex
      and hippocampus of Alzheimer's disease patients.
AB  - We examined brains from Alzheimer's disease (AD) patients by immunohistochemistry
      for the presence of protease inhibitors. Immunoreactivity for alpha 2
      macroglobulin (alpha 2-M), the most potent of the known human protease
      inhibitors, was found in a subgroup of cortical and hippocampal AD senile
      plaques. In addition, large hippocampal neurons in AD brains displayed
      intracellular alpha 2-M immunoreactivity which was consistently stronger than in
      normal aged brains. In cultured human cells of neurogenic origin (SH-SY5Y
      neuroblastoma cells), alpha 2-M synthesis could be strongly induced by the
      inflammatory cytokine interleukin-6 (IL-6) indicating that human alpha 2-M
      behaves as an acute-phase protein in the nervous system. Therefore, we also
      examined AD brains for the presence of IL-6 and found strong immunostaining in
      and around a subgroup of senile plaques as well as around large cortical neurons.
      Only very few senile plaques also stained for C-reactive protein, an acute phase
      protein known to be inducible by IL-6. We propose that the presence of IL-6 and
      alpha 2-M immunoreactivity in AD brains is functionally linked and that a
      sequence of immunological events is part of the pathology of AD.

PMID- 1370968
TI  - Prolonged monocyte accumulation in the lung during bleomycin-induced pulmonary
      fibrosis. A noninvasive assessment of monocyte kinetics by scintigraphy.
AB  - It has become more evident that monocytes, macrophages, and their products
      interact in a complex manner with various cell types in the lung, and may under
      the proper set of conditions contribute to the pathogenesis of pulmonary
      fibrosis. Current methods used to assess the lung content of mononuclear cells,
      which include tissue immunohistochemistry and bronchoalveolar lavage fluid
      analysis, sample the lung at one point in time and therefore provide only a
      "snapshot" of dynamic process. We utilized external imaging (scintigraphy) to
      provide a dynamic assessment of the trafficking patterns of radiolabeled
      monocytes in the lungs of rabbits in conjunction with lung tissue morphometry and
      bronchoalveolar lavage fluid analysis to determine the kinetics of neutrophil and
      monocyte accumulation in the alveolar walls and alveolar spaces of the lung
      during bleomycin-induced pulmonary fibrosis. We found that scintigraphy
      accurately reflected the accumulation of monocyte-associated radioactivity in the
      alveolar walls over time as well as the subsequent migration of these cells into
      alveolar spaces during the acute phase of bleomycin-induced lung injury (days 0
      to 14) when compared with lung tissue morphometry. The scintigraphy, lavage, and
      morphometry data together showed that neutrophil influx into both of these lung
      compartments preceded that of monocytes by days, and that the influx of monocytes
      accounted for a major proportion of mononuclear cells found in the alveolar walls
      and alveolar spaces of the lung during this acute phase of inflammation. The
      increased numbers of neutrophils and mononuclear cells in alveolar spaces
      normalized by days 14 and 28 respectively, but in contrast to the normalization
      of neutrophil content in alveolar walls by day 10, increased numbers of
      mononuclear cells persisted in alveolar walls for up to 56 days, a time when
      there was a significant increase in the hydroxyproline content of these lungs.
      These data also show that the increased number of mononuclear cells present in
      the alveolar walls on days 28 and 56 was not due to a persistent influx of blood
      monocytes. These data suggest: (a) that differential pathways of efflux existed
      for alveolar wall versus alveolar space mononuclear cells, (b) that a delay in
      efflux from the alveolar walls occurred and/or that an increase in the local
      proliferation of mononuclear cells in this compartment may have been occurring
      during the later phases of bleomycin-induced lung injury, and (c) that this
      prolonged residence of mononuclear cells in the alveolar walls occurred
      concurrently with the development of pulmonary fibrosis.

PMID- 1370969
TI  - Normal-hearing and hearing-impaired subjects' ability to just follow conversation
      in competing speech, reversed speech, and noise backgrounds.
AB  - The performance on a conversation-following task by 24 hearing-impaired persons
      was compared with that of 24 matched controls with normal hearing in the presence
      of three background noises: (a) speech-spectrum random noise, (b) a male voice,
      and (c) the male voice played in reverse. The subjects' task was to readjust the
      sound level of a female voice (signal), every time the signal voice was
      attenuated, to the subjective level at which it was just possible to understand
      what was being said. To assess the benefit of lipreading, half of the material
      was presented audiovisually and half auditorily only. It was predicted that
      background speech would have a greater masking effect than reversed speech, which
      would in turn have a lesser masking effect than random noise. It was predicted
      that hearing-impaired subjects would perform more poorly than the normal-hearing
      controls in a background of speech. The influence of lipreading was expected to
      be constant across groups and conditions. The results showed that the hearing
      impaired subjects were equally affected by the three background noises and that
      normal-hearing persons were less affected by the background speech than by noise.
      The performance of the normal-hearing persons was superior to that of the hearing
      impaired subjects. The prediction about lipreading was confirmed. The results
      were explained in terms of the reduced temporal resolution by the hearing
      impaired subjects.

PMID- 1370970
TI  - The role of dextran 40 and potassium in extended hypothermic lung preservation
      for transplantation.
AB  - We have previously demonstrated that a low-potassium dextran solution provides
      superior and more reliable preservation of lungs for 12 hours than that provided
      by the commonly used Euro-Collins solution. This study was designed to examine
      the individual contributions of dextran 40 and a low (extracellular) potassium
      concentration to lung preservation. In a randomized, blinded study using an in
      vivo canine single-lung transplant model, lungs preserved with low-potassium
      dextran solution (K+, 4 mmol/L; dextran 40, 20 gm/L) were compared to lungs
      preserved with low-potassium, no-dextran solution (K+, 4 mmol/L) and high
      potassium dextran solution (K+, 123 mmol/L; dextran 40, 20 gm/L). The lungs were
      assessed immediately and 3 days after transplantation. The low-potassium dextran
      solution provided excellent immediate pulmonary function with little variability
      (arterial oxygen tension, 519 +/- 12 mm Hg, measured on the transplanted lung
      alone, inspired oxygen fraction = 1.0, n = 6). Removing the dextran 40 from the
      flush solution (low-potassium group) led to a significant deterioration in
      pulmonary function (arterial oxygen tension, 243 +/- 78 mm Hg, n = 6, p less than
      0.01). The high-potassium dextran solution provided extremely poor preservation
      (arterial oxygen tension, 176 +/- 79 mm Hg; n = 6; p less than 0.01). Two animals
      in this group died within 6 hours of operation. Viability of the transplanted
      bronchus was significantly improved with the two solutions containing dextran 40.
      These results indicate that dextran 40 and low potassium concentration both
      contribute significantly to the uniformly excellent 12-hour lung preservation
      seen with the low-potassium dextran solution.

PMID- 1370971
TI  - Improved lung preservation with dextran 40 is not mediated by a superoxide
      radical scavenging mechanism.
AB  - Improved lung preservation with a low-potassium dextran-containing solution has
      been previously demonstrated. In a subsequent study, it was shown that dextran 40
      contributes significantly to this improved preservation. In the current in vitro
      study, human neutrophils suspended in lung preservation solutions (low potassium
      with dextran and low potassium without dextran) were stimulated to produce
      superoxide radicals. The presence of dextran in the solution did not
      significantly alter the amount of superoxide measured in the assay (low potassium
      with dextran, 4.149 +/- 0.144 nmol/10(6) cells/20 min; low potassium without
      dextran, 3.896 +/- 0.215; p greater than 0.2). This suggests that dextran 40 did
      not appreciably scavenge superoxide radicals, nor did it alter the production of
      superoxide radicals by stimulated neutrophils. Thus the significantly improved
      lung preservation seen with the use of dextran 40 is probably not mediated by a
      superoxide radical scavenging process.

PMID- 1370972
TI  - Reply to invited letter concerning: Aprotinin (J Thorac Cardiovasc Surg 1991;
      101:1103-4)

PMID- 1370973
TI  - Reoperation and mortality after surgical treatment of benign prostatic
      hypertrophy in a large prepaid medical care program.
AB  - The incidence of reoperation and mortality after prostatectomy was studied in
      8,219 men who underwent surgical treatment for benign prostatic hypertrophy
      between 1976 and 1987 while they were members of the Kaiser Permanente Medical
      Care Program, Northern California Region. The vast majority (94.5%) received
      transurethral prostatectomy (TURP). The cumulative 8-year probability of a second
      prostatectomy was 7.6% after TURP and 2.1% after open prostatectomy. The risk of
      mortality associated with transurethral prostatectomy relative to open
      prostatectomy was 1.6 (95% confidence interval 1.2, 2.1) 8 years postsurgery. The
      increased risk of mortality associated with transurethral prostatectomy was most
      prominent during the first 5 years postsurgery (relative risk 1.8, 95% confidence
      interval 1.3, 2.5) and declined to 1.1 (95% confidence interval 0.8, 1.6) for
      deaths occurring after the first 5 years. The finding of an increased risk of
      mortality associated with transurethral prostatectomy is consistent with other
      studies and is unexplained.

PMID- 1370974
TI  - The acute-phase response to turpentine-induced abscesses in malnourished rats at
      different environmental temperatures.
AB  - An assessment was made of the independent effect environmental temperature (13,
      21, and 30 degrees C) and either protein deficiency or energy deficiency on the
      metabolic response of rats that had aseptic abscesses induced by subcutaneous
      injections of turpentine. Measurements of food intake, alpha 2-macroglobulin
      (alpha 2-M; a major acute-phase protein in the rat), albumin, and various
      circulating metabolites were made 48 hours after turpentine injection in animals
      acclimatized at 13, 21, and 30 degrees C and compared with pair-fed controls.
      Despite differences in basal circulating albumin concentrations between controls
      and protein deficient rats (P less than .001), turpentine produced a similar
      reduction in all groups of animals (approximately 10 g/L), independent of
      environmental temperature. The alpha 2-M response to turpentine was attenuated in
      all protein-deficient animals and also in the energy-restricted animals at 13
      degrees C. The increase in circulating 3-hydroxybutyrate (BOH) and nonesterified
      fatty acid (NEFA) concentrations, which normally occur with reduced dietary
      intake, was reduced in the turpentine-injected animals to an extent that depended
      on prior dietary intake. It is concluded that the metabolic response,
      particularly the acute-phase protein response, to a standard form of "injury" is
      affected by protein deficiency and possibly by energy restriction under adverse
      environmental temperature.

PMID- 1370975
TI  - Acetyl-coenzyme A carboxylase mRNA metabolism in the rat liver.
AB  - The acetyl-coenzyme A carboxylase (ACC) gene contains two promoters (PI and PII),
      both of which are active in the liver. Various physiological stimuli affect one,
      or both of the promoters of the ACC gene, and result in the generation of two
      classes of ACC mRNAs which differ in the composition of their 5' untranslated
      regions (5' UTR). We have analyzed the amounts of the two major mRNAs species
      that are generated from each of these promoters in order to examine the
      regulation of ACC gene activity in the liver under different physiological
      conditions. Our findings can be summarized as follows: (1) In liver from normal
      animals, fed a complete laboratory chow ad libitum, the level of class 2 ACC mRNA
      species generated by PII is very low. These mRNA species disappear on starvation.
      Refeeding starved animals with a fat-free diet stimulates both PI and PII with
      different time courses of induction: PII responds quickly and PII gene products
      accumulate to maximum levels within 18 hours, while the PI response, as measured
      by the accumulation of class 1 mRNAs, shows a lag period of 6 hours before
      reaching maximal levels at the end of a 24-hour refeeding period. The half-lives
      estimated from the induction kinetics were 4.4 hours for class 2 mRNAs and 11.8
      hours for class 1 mRNAs. Reinstatement of starvation causes an almost
      instantaneous disappearance of class 1 mRNA species, as compared with class 2
      mRNA species. This rapid decay of PI transcripts suggests that factors
      stabilizing this class of ACC mRNAs contribute to the steady-state levels reached
      after the dietary induction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1370976
TI  - Extreme heterogeneity of Ty1-copia group retrotransposons in plants.
AB  - We have used the polymerase chain reaction to analyse Ty1-copia group
      retrotransposons of flowering plants. All eight species studied contain reverse
      transcriptase fragments from Ty1-copia group retrotransposons. Sequence analysis
      of 31 subcloned fragments from potato reveals that each is different from the
      others, with predicted amino acid diversities between individual fragments
      varying between 5% and 75%. Such sequence heterogeneity within a single species
      contrasts strongly with the limited diversity seen in such retrotransposons in
      yeast and Drosophila. The fragments from the other seven plant species examined
      are also heterogeneous, both within and between species, showing that this is a
      general property of this transposon group in plants. Phylogenetic analysis of all
      these sequences reveals that many of them fall into subgroups which span species
      boundaries, such that the closest homologue of one sequence is often from a
      different species. We suggest that both vertical transmission of Ty1-copia group
      retrotransposons within plant lineages and horizontal transmission between
      different species have played roles in the evolution of Ty1-copia group
      retrotransposons in flowering plants.

PMID- 1370978
TI  - Differential expression and stability of foreign genes introduced into human
      fibroblasts by nuclear versus cytoplasmic microinjection.
AB  - We have compared cytoplasmic- and nuclear-delivered, glass needle-mediated
      microinjection protocols for their ability to support both transient and stable
      phenotypic expression of reporter gene constructs in non-immortalized human skin
      fibroblasts cultures. Microinjection of form I (covalently closed circular,
      supercoiled) plasmid pMC38 DNA into the nucleus of human cells resulted in high
      levels of transiently expressed p110gag-myc oncoprotein as detected by
      immunofluorescence microscopy. Likewise, the nuclear delivery of a plasmid
      construct bearing the entire simian virus 40 genome induced the formation of
      morphologically transformed foci in approximately 6% of the recipient cell
      population. In contrast, the introduction of plasmid DNA by the cytoplasmic route
      proved virtually incapable of supporting either transient gene expression or
      morphological transformation. In situ autoradiography of cells injected with 3H
      labelled plasmid DNA revealed that whereas the material delivered directly into
      the nucleus was retained by this subcellular compartment for prolonged times
      (greater than or equal to 48 h), the radiolabelled DNA molecules introduced via
      the cytoplasmic route did not reach the nucleus and appeared to be substantially
      degraded within 8 h following injection. These results indicate unequivocally
      that nuclear injection is the route of choice when monitoring foreign gene
      expression in human cells.

PMID- 1370977
TI  - Characterization of a UV-damage recognition factor in vitro that is associated
      with UV resistance in HeLa cells.
AB  - We have previously reported a cisplatin-selected HeLa cell line showing cross
      resistance to ultraviolet (UV) radiation and overexpression of UV-damage
      recognition factors (Chao et al., Mol. Cell. Biol., 11, 2075-2080, 1991). Here,
      we further characterize a UV-damage recognition factor in vitro using a gel
      mobility shift assay. The results indicate that the damage-recognition factor is
      (i) localized mostly in the nucleus, (ii) protease-sensitive, (iii) RNA
      independent, (iv) active in a wide range of ionic strengths (50-400 mM NaCl), (v)
      with a high affinity for UV-damaged DNA (50-fold molar excess competitor causes
      50% recognition loss), and (vi) resistant to agents and that modify protein
      conformation (urea and NP-40), but slightly sensitive to CaCl2. The significance
      of the identified UV-damage recognition factor in the sensitivity or resistance
      of cells to UV is also discussed.

PMID- 1370979
TI  - Overproduction of the RecD polypeptide sensitizes Escherichia coli cells to gamma
      radiation.
AB  - We investigated DNA metabolism in Escherichia coli cells carrying the multicopy
      recD+ plasmid (pKI13). In the presence of pKI13, the cellular level of the recD
      gene product (RecD polypeptide) is amplified at least 60-fold. Overproduction of
      the RecD polypeptide has no effect on UV repair and conjugational recombination.
      In contrast, high cellular levels of this polypeptide sensitize wild-type cells
      to gamma-radiation; also, they increase the rate of radiation-induced DNA
      degradation. A possible mechanism for the enhancement of gamma-ray-induced
      killing by large amounts of the RecD polypeptide is discussed.

PMID- 1370980
TI  - The persistence of sister-chromatid exchange frequencies in men occupationally
      exposed to vinyl chloride monomer.
AB  - The persistence of sister-chromatid exchange frequencies in a population
      occupationally exposed to the well known chemical mutagen vinyl chloride monomer
      was studied. It was shown that increased values of sister-chromatid exchange
      frequencies were still present in the lymphocytes of workers who had not been
      exposed for 8-120 days and retired persons for 5-10 years after exposure. The
      possible ability of vinyl chloride monomer alkylating metabolites to cause long
      lasting damage of the DNA molecule is discussed.

PMID- 1370981
TI  - No increase in chromosome aberrations in lymphocytes from workers exposed to
      nitrogen fertilisers.
AB  - The putative genetic risk of people occupationally exposed to nitrogen
      fertilisers was studied using the structural chromosome aberration assay in
      peripheral blood lymphocytes. The exposed group included 23 subjects working at
      complex and mixed fertiliser plants. The percent of aberrant cells (Ab.C %) and
      break to cell ratio (B/C) were 0.95% and 0.01 respectively. The matched control
      group (20 subjects) was found to have 0.80% Ab.C and a B/C ratio of 0.0085. The
      results show a lack of detectable genetic damage in exposed people using this
      cytogenetic approach.

PMID- 1370982
TI  - SOS system induction in Escherichia coli cells with distinct levels of
      ribonucleotide reductase activity.
AB  - The UV-mediated induction of recA and sfiA genes in Escherichia coli cells with
      distinct levels of dATP has been studied. Low levels of dATP were obtained by
      using either a temperature-sensitive ribonucleotide (RDP) reductase-deficient
      (nrdA) mutant or a wild-type strain treated with hydroxyurea. High pools of dATP
      were achieved by using a plasmid overproducing RDP reductase. The results
      obtained show that expression of the recA and sfiA genes was inhibited neither in
      the UV-irradiated nrdA mutant at 42 degrees C nor in the wild-type strain in the
      presence of hydroxyurea. Likewise, the increase of the dATP pool did not enhance
      recA and sfiA gene expression after UV irradiation. All these data suggest that
      the basal level of dATP is not a limiting factor in the process of induction of
      the SOS system in Escherichia coli.

PMID- 1370983
TI  - Mutagenicity of pyrrolizidine alkaloids in the Salmonella typhimurium/mammalian
      microsome system.
AB  - The mutagenicity of a series of pyrrolizidine alkaloids, and of extracts from
      several Italian Senecio species containing pyrrolizidine alkaloids, including S.
      inaequidens, S. fuchsii and S. cacaliaster, were tested using the Salmonella
      typhimurium/mammalian microsome system. Retrorsine, senecivernine, seneciphylline
      and the Senecio extracts showed a weakly mutagenic activity.

PMID- 1370984
TI  - The protective role of polyphenols in cytotoxicity of hydrogen peroxide.
AB  - A variety of synthetic and natural polyphenols protect mammalian cells from
      hydrogen peroxide (H2O2). Cytotoxicity of H2O2 on Chinese hamster V79 cells was
      assessed with a colony formation assay, and several polyphenols prevented the
      decrease in the number of colonies caused by H2O2. A study of the structure
      activity relationship revealed that affinity of the polyphenols for the cell
      membrane and the presence of an ortho-dihydroxy moiety in their structure proved
      essential to this protection.

PMID- 1370985
TI  - Frameshift mutagenesis in bacteriophage T7.
AB  - We have undertaken an initial characterization of frameshift mutagenesis in
      bacteriophage T7 and have identified a subset of very low reversion frameshift
      mutations in the T7 ligase gene (gene 1.3). We used this information to construct
      bacteriophage T7 strains that contain one extra or one less base pair in gene 1.3
      such that a frameshift event restores the reading frame of that gene. These
      events can be quantified and the frameshift mutation isolated within a localized
      region of the ligase gene. We have also identified a portion of the T7 ligase
      protein that will accept tracts of nonsense amino acids yet still give a ligase
      positive phenotype. This allows flexibility in the design of the target DNA
      sequence with which to study frameshift mutagenesis. These assays for frameshift
      mutagenesis performed in E. coli cells infected with the appropriate T7 strain,
      were used to measure the frequency of both plus and minus frameshifts in vivo.

PMID- 1370986
TI  - The effect of lead on Allium cepa L.
AB  - The effect of lead on Allium cepa L. at concentrations of 0.1, 1.0, 10, 50, 100
      and 200 ppm were studied. Analysis focused on root growth, frequency of mitosis
      in a meristematic zone, and chromosomal aberrations. It was observed that lead
      reduces root growth and the frequency of mitotic cells in meristematic zones, and
      increases the frequency of aberrant cells. The intensity of the effects is a
      function of lead concentration.

PMID- 1370987
TI  - Further studies on the mutagenic activity of fecapentaene-12 analogues and
      conclusions about their molecular mode of action.

PMID- 1370988
TI  - Clastogenic activity of urethane in mice.
AB  - Single intraperitoneal (i.p.) treatment of male and female BDF1 (C57B1 x DBA2)
      mice with urethane (0.5 or 1.0 g/kg) caused a significant increase in
      micronucleated polychromatic erythrocytes (MNPCE) in bone marrow after 24 h. The
      clastogenic effect observed was dose-, sex- and age-dependent, the male and
      younger (6-8 weeks old) animals being more susceptible than the female and older
      (6 months of age) mice. 3-week oral treatment of female Balb/c mice with urethane
      (3 g/l added to the drinking water) caused an up to 4-fold increase in the number
      of micronucleated normochromatic erythrocytes (MNNCE) in mouse peripheral blood.
      In a month after the carcinogen treatment was stopped, the number of MNNCE
      dropped to the control values. In addition, a single i.p. treatment of pregnant
      BDF1 mice on day 17 of gestation with urethane (1.0 g/kg) caused a 514.3% (p less
      than 0.001) elevation of MNPCE in mouse fetal liver after 24 h as well as a
      154.4% (p less than 0.05) increase in MNPCE frequency in the fetal peripheral
      blood. At this time point, the clastogenic response in mouse fetal liver
      erythroblasts was less pronounced than that detected in the maternal bone marrow
      cells. Urethane is a strong clastogen in mice when administered either
      intraperitoneally or orally and the micronucleus test applied to adult and fetal
      erythroblasts is a convenient method of choice for studying the acute and
      subchronic clastogenicity of this carcinogen, its transplacental effects as well
      as the influence of modifying factors on these processes.

PMID- 1370989
TI  - Implantable cardioverter defibrillator: the promise and perils of an evolving
      technology.

PMID- 1370990
TI  - Long-term results of nervous tissue alterations caused by epineurial electrode
      application: an experimental study in rat sciatic nerve.
AB  - In order to evaluate the long-term effects of epineurial electrode application
      for functional electrical stimulation (FES) the left sciatic nerve of seven rats
      was exposed. Four ring-shaped stainless steel wire electrodes were sutured to the
      epineurium of each nerve in the same manner as performed clinically for carrousel
      stimulation in man. The nerves were reexposed 1 year after implantation and the
      stimulation threshold to obtain a tetanic contraction in the lower limb was
      determined for each electrode. Afterwards the animals were sacrificed. The
      electrodes were excised and cross sections of the sciatic nerve directly at site
      of the electrodes, 2-mm proximal and 2-mm distal to them were harvested for
      histologic and planimetric assessment of nerve lesions. The area of damaged
      neural tissue was expressed as a percentage of the total cross-sectional area
      within the perineural sheath. The sciatic nerves of the right side served as
      controls. The values for the stimulation thresholds ranged between 0.1 and 1.0 mA
      (mean 0.43 mA). By morphometric examination five of seven nerves were seen
      altered, the altered areas captured between 1% and 4.8% of the total cross
      sectional area of the nerves within the perineural sheath. Besides two specimens,
      all altered nerve segments exhibited distinct signs of nerve fiber regeneration.
      The clinical implications of the results for long-term electrical stimulation,
      such as phrenic pacing, are discussed.

PMID- 1370992
TI  - Amplitude and direction of atrial depolarization using a multipolar floating
      catheter: principles for a single lead VDD pacing.

PMID- 1370991
TI  - Atrial latency in a dual chambered pacing system causing inappropriate sequence
      of cardiac chamber activation.
AB  - A transvenous atrioventricular pacemaker was implanted in a patient in whom
      junctional bradycardia and recurrent ventricular tachycardia had occurred after
      coronary artery bypass surgery. The period between delivery of the atrial
      stimulus and resultant atrial excitation was prolonged by up to 0.22 seconds and
      exceeded the programmed delay between atrial and ventricular stimulation.
      Consequently, ventricular stimulation preceded atrial excitation. Cardiac failure
      resulted: it was resolved by reprogramming the pacemaker to the atrial inhibited
      mode.

PMID- 1370993
TI  - Performance of implantable cardiac rhythm management devices.

PMID- 1370994
TI  - Prolonged asystole during head-up tilt table testing after beta blockade.
AB  - Neurally mediated vasodepressor syncope is a common clinical problem. The
      diagnosis is generally associated with a benign prognosis, however, a less common
      "malignant" form has been identified. Head-up tilt table testing is helpful in
      the confirmation of the diagnosis of neurally mediated vasodepressor syncope and
      may be useful in the selection of therapy. One form of therapy commonly used is
      beta blockade. In this case report we describe a patient with neurally mediated
      vasodepressor syncope who developed asystole during head-up tilt table testing
      after treatment with a beta blocker.

PMID- 1370995
TI  - Follow-up of a respiratory rate modulated pacemaker.
AB  - The efficacy of 27 respiration sensitive rate modulated pacemakers (Biorate RDP-3
      Biotec) implanted in the left pectoral area was evaluated every 3 months during a
      mean follow-up period of 29 months (range 10-50 months). Rate modulation function
      was unchanged other than for three patients in whom the auxiliary leads became
      displaced. Two implants lost ventricular sensing in this nonprogrammable model.
      In all but the three patients, Holter monitoring demonstrated pacing rate
      variation corresponding to daily activity. Stress test duration increased from
      8.2 +/- 1.5 minutes (in fixed rate VVI rate) to 12.83 +/- 2.0 minutes (in the
      VVIR mode) (P less than 0.05). Right arm movement increased the pacing rate by 5
      +/- 3 beats/min (NS), while the left arm movement increase was 30 +/- 5 beats/min
      (P less than 0.05). Mental, arithmetic, and nifedipine tests did not change the
      rate modulated pacing rate. The system responded to a change in respiratory rate
      by an increase in stimulation rate. A satisfactory response in sensitivity and
      velocity was present only with medium-high workloads. Interference with rate
      modulation occurred with movement of the arm ipsilateral to the implanted pulse
      generator.

PMID- 1370996
TI  - Impedance monitoring during radiofrequency catheter ablation in humans.
AB  - Radiofrequency catheter ablation of accessory pathways and the atrioventricular
      junction often requires multiple applications of energy. The inability to
      determine the effects of any given application on the underlying tissue may
      contribute to this problem. In the present study, impedance was monitored in 20
      patients undergoing radiofrequency catheter ablation, and the relationship
      between an initial decrease in impedance and subsequent effects were examined. An
      initial fall in impedance of more than 10 omega was 78% sensitive and 88%
      specific for predicting subsequent evidence of tissue heating (interruption of
      conduction or an abrupt rise in impedance due to coagulum formation). In
      contrast, initial values of voltage, current, or impedance did not distinguish
      between effective and ineffective applications of radiofrequency energy.
      Continuous monitoring of impedance may facilitate radiofrequency catheter
      ablation.

PMID- 1370997
TI  - Double ventricular responses to a single atrial depolarization in a patient with
      dual AV nodal pathways.
AB  - Electrophysiological study was performed in a patient with atrioventricular nodal
      reentrant tachycardia (AVNRT). Double ventricular responses through dual AV nodal
      pathways were observed by atrial extrastimulus technique followed by initiation
      of AVNRT. The difference in conduction time between the slow and fast AV nodal
      pathways was longer than 320 msec. A ventricular extrastimulus delivered during
      sinus rhythm, which was not followed by ventriculoatrial conduction, also induced
      AVNRT. These findings indicated the presence of an antegrade critical delay and
      retrograde block in the slow AV nodal pathway, criteria necessary for the
      occurrence of a double ventricular response.

PMID- 1370998
TI  - The use of implantable sensors for the control of pacemaker mediated
      tachycardias: a comparative evaluation between minute ventilation sensing and
      acceleration sensing dual chamber rate adaptive pacemakers.
AB  - The role of implantable sensors to control pacemaker mediated tachycardias was
      investigated in 16 patients with two different dual chamber rate adaptive (DDDR)
      pacemakers, which sensed eiter minute ventilation (DDDR-Meta, nine patients) or
      body acceleration (Relay, seven patients). Successive atrial sensed events beyond
      a programmable rate occurring in the absence of detection of exercise by the
      sensors were considered to represent retrograde conduction or atrial arrhythmias,
      and the pacemakers responded by either a mode shift from DDDR to ventricular rate
      adaptive (VVIR) pacing (DDDR-Meta) or by tracking at an interim rate, the so
      called conditional ventricular tracking limit (CVTL, Relay). In the unipolar
      atrial sensing mode, myopotential sensing (MPI) and external chest wall
      stimulations (CWS) at 250 beats/min were induced to be preferentially sensed by
      the atrial channel to simulate the conditions of atrial arrhythmias. In the DDD
      mode, these maneuvers resulted in ventricular responses of 88 +/- 3 beats/min and
      110 +/- 3 beats/min for MPI and CWS, respectively. The pacing rate was
      significantly reduced in the DDDR mode with the sensors correctly detecting and
      responding to the sensed abnormal atrial signals (68 +/- 5 beats/min during MPI
      and 71 +/- 5 beats/min during CWS, P less than 0.005 compared with the
      corresponding DDD rate). One patient with a Relay pacemaker developed spontaneous
      atrial flutter and the ventricular tracking responses were 140 and 85 beats/min
      in the DDD and DDDR pacing modes, respectively. Thus MPI and CWS are useful
      bedside testing methods to assess pacemaker response during atrial arrhythmias.
      The use of implantable sensors to judge the appropriateness of atrial rate is a
      new approach to the management of pacemaker mediated tachycardias.

PMID- 1370999
TI  - Simultaneous unipolar and bipolar recording of cardiac electrical activity.
AB  - An analog mapping system using a true bipolar left ventricular balloon electrode
      array is described, which enables simultaneous unipolar and bipolar recordings.
      It is an adaptation of a previous clinical analog mapping system used in the
      investigation of ventricular arrhythmias. The bipolar balloon array consists of
      112 electrode pairs, each having a 2-mm separation. The signals from the
      electrodes are sensed in parallel by separate unipolar and bipolar amplifier
      units, which then drive a common multiplexer bus. The bipolar recording unit
      consists of high quality instrumentation amplifiers with adjustable gain and
      exhibits a full bandwidth minimum common mode rejection of 78 dB. Using this
      combination, it is possible to record local cardiac micropotentials while still
      retaining the advantages of unipolar electrograms to track overall cardiac
      activation.

PMID- 1371000
TI  - Myocardial rupture after pulling out a tined atrial electrode with continuous
      traction.
AB  - Transvenous traction for the removal of retained pacemaker electrodes is common
      practice with few reported complications. This case reports a patient with a DDD
      pacemaker with extruded electrodes, who died of a myocardial rupture at the
      atrial lead site after prolonged (i.e., after 24 hours) traction was applied.

PMID- 1371001
TI  - Nd:YAG laser-photocoagulation: acute electrophysiological, hemodynamic, and
      morphological effects in large irradiated areas.
AB  - Laser-photocoagulation (LPC) of arrhythmogenic myocardium has been reported to
      successfully ablate ventricular tachycardia. The purpose of this study was to
      investigate the acute hemodynamic and electrophysiological effect of continuous
      laser energy (Nd:YAG, 1060 nm) applied via a 0.4-mm quartz fiberoptic on the
      epicardial surface of the heart in nine dogs. A total of 51 +/- 2.3 pulses was
      delivered in each animal to induce homogeneous tissue necrosis. Applied energy
      was 12.3 +/- 2.7 J/mm2, irradiated surface measured 12.6 +/- 3.0 cm2, lesion
      depth was 6.3 +/- 1.2 mm (range: 5.0-8.1 mm), lesion volume was 8.1 +/- 2.8 cm3
      (6.8% of left ventricular [LV] mass). After LPC, epicardial stimulation threshold
      significantly rose from 1.0 +/- 0.3 to 10.2 +/- 4.9 mA in the border zone to
      nontreated tissue and from 0.9 +/- 0.4 to 32 +/- 15.7 mA in the center of the
      lesions. Loss of epicardial activation in the irradiated areas could be
      demonstrated by epicardial mapping. Ventricular extrasystoles during LPC were
      seen in all dogs, ventricular tachycardia in seven, and ventricular fibrillation
      in two dogs. After LPC, cardiac output and LV dP/dtmax significantly decreased by
      14.2% and 11.2%. LPC induced predictable homogeneous tissue edema, eosinophilic
      staining, contraction band necrosis, and sharp demarcated hemorrhagic border
      zones with a sharp electrical border zone to nontreated tissue and loss of
      epicardial activation. During LPC, various arrhythmogenic effects could be
      observed. However, no persistent arrhythmic activity developed after LPC. The
      results confirm the feasibility of epicardial LPC of the myocardium. Although not
      rested in this study, LPC of arrhythmogenic tissue may also be feasible as a
      treatment modality of ventricular tachycardia.

PMID- 1371002
TI  - Analysis of deaths in patients with an implantable cardioverter defibrillator.
AB  - The cause of death and clinical characteristics of 26 patients that died after
      implantable cardioverter defibrillator placement were reviewed and compared to
      the 145 patients still living after a mean follow-up of 17 months. Operative
      mortality was 4% (7/171) and resulted from postoperative ventricular arrhythmias
      (four patients), heart failure (two patients), and respiratory failure (one
      patient). Operative mortality was significantly higher (1.7% vs 9.6%, P less than
      0.05) following concomitant surgical procedures. Total late mortality was 11%
      (18/171). Thirteen deaths (75%) occurred in-hospital from progressive
      deterioration of left ventricular function (nine patients), arrhythmia (two
      patients), and noncardiac causes (two patients). Outpatient mortality was 3.5%
      (6/171) and resulted from presumed sudden cardiac death in five of six patients;
      two of the five had devices that were inactive, one had high defibrillation
      thresholds, and two had suspected bradyarrhythmic deaths. One postoperative death
      and one late in-hospital death were also considered sudden cardiac deaths for a
      total of seven patients with defibrillation system failures. By multivariant
      analysis, preoperative clinical characteristics associated with a worse prognosis
      following defibrillator implantation were identified: presentation as ventricular
      tachycardia (P less than 0.02), induction of sustained monomorphic ventricular
      tachycardia (P less than 0.05), poor left ventricular performance (P less than
      0.01), poor functional status (P less than 0.001), and the use of diuretics (P
      less than 0.01). Frequent device discharges (P less than 0.001) and concomitant
      antitachycardia pacing systems (P less than 0.001) were markers for greater
      arrhythmia recurrence and were potent predictors of a worse prognosis and
      particularly sudden death.

PMID- 1371003
TI  - Atrial vulnerability and electrophysiology determined in patients with and
      without paroxysmal atrial fibrillation.
AB  - For elucidation of atrial electrophysiology and vulnerability an
      electrophysiological study was performed in 45 patients with documented
      paroxysmal atrial fibrillation and a control group (n = 46). Atrial vulnerability
      was assessed by programmed atrial stimulation with up to two extrastimuli during
      sinus rhythm and paced cycle lengths of 600 msec, 430 msec and 330 msec.
      Sustained atrial fibrillation or flutter was induced in 37/45 patients with
      paroxysmal atrial fibrillation in contrast to 9/46 patients in the control group
      (P less than 0.001). Left atrial diameter (M-mode echocardiogram), P wave
      duration, sinus cycle length, sinus node recovery time, and the effective
      refractory period of the right atrium were not significantly different between
      the two study groups. Intraatrial conduction time from the high right atrium
      (HRA) to the basal right atrium (A) and the functional refractory period of the
      right atrium were significantly longer in patients with paroxysmal atrial
      fibrillation.

PMID- 1371004
TI  - The effect of magnetic resonance imagers on implanted neurostimulators.
AB  - This in-vitro study was designed to investigate the safety of various implanted
      neurostimulators in magnetic resonance (MR) imagers. The effects of the static
      and changing magnetic fields and the radio frequency (RF) electromagnetic field
      generated by 0.35 and 1.5 T MR imagers on the voltage output of four models of
      implantable passive neurostimulators and two models of implantable self-powered
      neurostimulators was studied. The neurostimulators were mounted on a support and
      placed in the imagers. An oscilloscope monitored the voltages at the outputs of
      the neurostimulators. For an Avery single-channel stimulator, located at the
      isocenter, the amplitude of the output pulses induced by the 0.35 T imager was
      6V; from a 1.5 T imager, it was 12 V. These amplitudes can cause discomfort and
      possible harm to a patient if the typical therapeutic value is 1-5 V. The
      amplitude of the stimulator receiver's output decreased to relatively safe values
      beyond 40 cm from the isocenter. By contrast, there was no significant voltage
      output from the Medtronic SE-4 receiver. For two models of self-powered
      neurostimulators, the Medtronic Itrel and the Cordis MK II, the programmed
      stimulus parameters were not affected by the pulsed magnetic fields of the MR
      imagers. However, the RF fields at the isocenter heated the metal case of the
      stimulators. The rotational and linear forces produced by the fixed magnet on the
      Cordis MK II were judged to be too strong for a patient with this implant to be
      scanned. The study showed that patients with certain types of implanted
      neurostimulators can be scanned safely under certain conditions.

PMID- 1371005
TI  - Serum creatine kinase activity and sensing characteristics after intraoperative
      arrhythmia induction using implantable defibrillator rate sensing leads.
AB  - In 29 patients (24 men, 5 woman, mean age 57 +/- 14 years) we evaluated the
      effect of intraoperative arrhythmia induction during implantable defibrillator
      (ICD) placement using alternating current (AC) applied through the epicardial
      rate sensing leads on acute and chronic pacing thresholds, electrogram
      amplitudes, slew rates and serum creatine kinase levels. In 15 patients
      undergoing new ICD implantation, pacing thresholds, electrogram amplitudes, slew
      rates, and resistances were measured before and following at least three
      inductions of ventricular fibrillation (VF) using AC applied through the
      epicardial rate sensing leads. Fourteen patients who underwent VF induction using
      AC through the epicardial leads during initial implant (mean time of 31 months
      previously) underwent ICD pulse generator replacement only with parameters
      measured as above before and after at least two inductions, and these compared to
      the values at initial implant. In all 29 patients serum creatine kinase levels
      were obtained before, immediately following, and at 8, 16, and 24 hours after
      surgery. No significant change in acute pacing threshold, electrogram amplitude,
      slew rate or resistance occurred. Chronically there was an expected 154% increase
      in pacing threshold but no significant change in electrogram amplitude or
      resistance. Serial serum creatine kinase and MB isoenzyme determinations
      demonstrated no evidence of myocardial necrosis. We conclude that intraoperative
      arrhythmia induction during ICD implantation using AC applied through the rate
      sensing leads is a safe and effective technique.

PMID- 1371006
TI  - The electrode-tissue interface: the revolutionary role of steroid elution.

PMID- 1371007
TI  - Argyrophilic nucleolar organizer regions in benign hyperplastic and cancerous
      human prostates.
AB  - Argyrophilic nucleolar organizer regions (AgNORs) were examined histologically in
      cells of benign hyperplastic and cancerous human prostates. Individual dots of
      AgNORs inside nucleus that were stained as separate granules or as parts of
      clusters were counted as one, and the average number of dots per cell was
      obtained by counting 100 nuclei. The number in epithelial cells was similar to
      that in stromal cells of hyperplastic prostates. In cancerous prostates, the
      number was larger than in hyperplastic prostates and increased along with
      upgrading. The number in incidental cancers was smaller than in clinical cancers
      as compared with cells of the same Gleason pattern. Number correlated with T
      factor, but not with N and M factors. Response to treatment and cause-specific
      survival in stage D2 patients receiving endocrine therapy did not correlate with
      number, although a relationship between Gleason pattern and survival was shown in
      these patients. It was concluded that AgNORs might not be an indicator to predict
      prognosis after endocrine therapy, since a number of AgNORs did not influence
      response to the therapy.

PMID- 1371008
TI  - Effects of extracellular matrix components and dihydrotestosterone on the
      structure and function of human prostate cancer cells.
AB  - The extracellular matrix (ECM) has been shown to play a major role in cell
      structure and function. Several studies have demonstrated that the ECM can alter
      cell morphology and effect DNA synthesis and gene expression. The ECM also
      interacts with growth hormones which have been shown to be located in or near the
      ECM where they are believed to effect cell structure and function. In the
      nontransformed cell, these ECM and hormone-mediated effects appear to be tightly
      regulated and this is believed to be accomplished through cell receptor-tissue
      matrix interactions. We, therefore, undertook a study to determine the effects of
      a variety of ECM components and the adrogenic hormone dihydrotestosterone (DHT)
      on the structure and function of the human prostate cancer cell line, LNCaP. The
      effects of individual matrix components in the presence and absence of 1 nM DHT
      on the static and dynamic morphology, growth rate, and PSA production of the
      LNCaP cell line were studied. We determine that the ECM and DHT interact in
      complex ways to effect cell structure and function. DHT produced alterations in
      cytoplasmic structure that increased cell size and decreased the nuclear
      area/cytoplasmic area ratio. Dynamic cell structure as measured by cell motility
      was very sensitive to the ECM components and the presence of DHT. PSA and growth
      could be regulated by substratum and DHT and there was an inverse relationship
      between PSA production and growth rate. These data exemplify the complex
      interactions which occur between prostate cancer cells, ECM components, and
      exogenous DHT that are reflected in cell structure and function.

PMID- 1371010
TI  - Onset of cell-specific gene expression in the developing mouse pancreas.
AB  - A central question in developmental biology has been the initiation of cell
      specific gene expression and its temporal relationship to morphogenesis. We have
      coupled embryo microdissection with the exquisite sensitivity of the polymerase
      chain reaction to define the onset of cell-specific gene expression during
      pancreatic organogenesis. Using the precise assignment of gestational age by the
      number of somites in each embryo, we determined the onset of transcription of
      major genes of the endocrine and exocrine pancreas during mouse development to
      within 2-3 hr. Somatostatin mRNA was detected at the 10-somite stage throughout
      the foregut, consistent with the presence of somatostatin-producing cells
      throughout the adult gut. Mature mRNA for insulin and glucagon first appears
      surprisingly early, at the 20-somite stage in the wall of the embryonic foregut
      and is restricted to only the area of the duodenum from which the pancreas will
      arise 10-12 hr later. In contrast, exocrine gene transcription begins 24 hr after
      formation of the pancreatic diverticulum. Thus cell-specific gene expression in
      the endocrine pancreas begins in a "pre-morphogenetic phase." This early
      expression of insulin and glucagon could reflect the initiation of an endocrine
      cell lineage.

PMID- 1371009
TI  - Activation of Src-like protein-tyrosine kinase Lyn and its association with
      phosphatidylinositol 3-kinase upon B-cell antigen receptor-mediated signaling.
AB  - Crosslinking of membrane-bound immunoglobulins, which are B-cell antigen
      receptors, causes proliferation and differentiation of B cells or the inhibition
      of their growth. The receptor-mediated signaling involves tyrosine
      phosphorylation of cellular proteins. The Src-like protein-tyrosine kinase Lyn is
      expressed preferentially in B cells and is an intracytoplasmic constituent of the
      B-cell antigen receptor complex. Crosslinking of membrane-bound immunoglobulin M
      with antibody induced rapid increases in the kinase activities of Lyn and Lyn
      associated phosphatidylinositol 3-kinase. Crosslinking of B-cell antigen receptor
      also induced association of Lyn with an 85-kDa noncatalytic subunit of
      phosphatidylinositol 3-kinase. Thus, Lyn is functionally associated with membrane
      bound immunoglobulin M and seems likely to participate in B-cell antigen receptor
      mediated signaling.

PMID- 1371011
TI  - Heterogeneous nuclear ribonucleoprotein A1 catalyzes RNA.RNA annealing.
AB  - Within the nucleus, pre-mRNA molecules are complexed with a set of proteins to
      form heterogeneous nuclear ribonucleoprotein complexes. A1, an abundant RNA
      binding protein present in these complexes, has been shown to bind selectively to
      single-stranded RNAs and destabilize base-pairing interactions. In this study.A1
      is shown to promote the rate of annealing of complementary RNA strands greater
      than 300-fold under a wide range of salt concentration and temperature. Maximal
      annealing is observed under saturating or near saturating concentrations of
      protein, but annealing decreases sharply at both higher and lower concentrations
      of A1. Kinetic analysis shows that the rate of annealing is not strictly first or
      second order with respect to RNA at a ratio of protein/RNA that gives optimal
      rates of annealing. This result suggests that A1 protein may affect more than one
      step in the annealing reaction. Two polypeptides representing different domains
      of A1 were also examined for annealing activity. UP1, a proteolytic fragment that
      represents the N-terminal two-thirds of A1, displays very limited annealing
      activity. In contrast, a peptide consisting of 48 amino acid residues from the
      glycine-rich C-terminal region promotes annealing at a rate almost one-quarter
      that observed with intact A1. The RNA.RNA annealing activity of A1 may play a
      role in pre-mRNA splicing and other aspects of nuclear mRNA metabolism.

PMID- 1371012
TI  - Host-cell-phenotype-dependent control of the BCR2/BWR1 promoter complex regulates
      the expression of Epstein-Barr virus nuclear antigens 2-6.
AB  - Epstein-Barr virus nuclear antigens (EBNAs) are expressed in a cell-phenotype
      dependent manner. EBNA 1 is regularly expressed in all Epstein-Barr virus
      carrying cells, whereas EBNAs 2-6 are only expressed in Epstein-Barr virus
      carrying cells with a lymphoblastoid phenotype including group III Burkitt
      lymphoma (BL) lines positive for B-cell activation markers. Transcripts are
      initiated at the BCR2 or exceptionally at one BWR1 promoter in lymphoblastoid
      cell lines and group III BL lines. In group I BL lines, nasopharyngeal carcinoma,
      and the somatic cell hybrids, where EBNAs 2-6 are downregulated, the BCR2/BWR1
      promoter complex is inactive or switched off. Upregulation of EBNAs 2-6 in group
      III BL cells and in 5-azacytidine-treated group I BL cells accompanies the
      activation of the silent BCR2/BWR1 promoters. Activation of BCR2 parallels
      demethylation of at least one CpG pair in the same promoter region. The activity
      of BCR2/BWR1 promoter complex depends on a particular B-cell phenotype. EBNA 1
      transcription must be initiated at another promoter in cells that express only
      EBNA 1.

PMID- 1371013
TI  - Extensive size polymorphism of the human keratin 10 chain resides in the C
      terminal V2 subdomain due to variable numbers and sizes of glycine loops.
AB  - Existing data suggest that the human keratin 10 intermediate filament protein is
      polymorphic in amino acid sequence and in size. To precisely define the nature of
      the polymorphism, we have used PCR amplification and sequence analyses on DNA
      from several individuals including five with documented size variations of the
      keratin 10 protein. We found no variation in the N-terminal or rod domain
      sequences. However, we observed many variations in the V2 subdomain near the C
      terminus in glycine-rich sequences with a variation of as much as 114 base pairs
      (38 amino acids), but all individuals had either one or two variants. Our results
      show that (i) the keratin 10 system is far more polymorphic than previously
      realized, (ii) the polymorphism is restricted to insertions and deletions of the
      glycine-rich quasipeptide repeats that form the glycine-loop motif in the C
      terminal domain, (iii) the polymorphism can be accounted for by simple allelic
      variations that segregate by normal Mendelian mechanisms, and (iv) the
      differently sized PCR products most likely represent different alleles of a
      single-copy gene per haploid genome.

PMID- 1371014
TI  - Double-stranded RNA-dependent RNase activity associated with human
      immunodeficiency virus type 1 reverse transcriptase.
AB  - Early events in the retroviral replication cycle include the conversion of viral
      genomic RNA into linear double-stranded DNA. This process is mediated by the
      reverse transcriptase (RT), a multifunctional enzyme that possesses RNA-dependent
      DNA polymerase, DNA-dependent DNA polymerase, and RNase H activities. In the
      course of studies of a recombinant RT of human immunodeficiency virus type 1 (HIV
      1), we observed an additional, unexpected activity of the enzyme. The purified RT
      catalyzes a specific cleavage in HIV-1 RNA hybridized to tRNALys, the primer for
      HIV-1 reverse transcription. The cleavage at the primer binding site (PBS) of HIV
      RNA is dependent on the double-stranded structure of the HIV RNA-tRNALys complex.
      This RNase activity appears to be distinct from the RNase H activity of HIV-1 RT,
      as the substrate specificity and the products of the two activities are
      different. Moreover, Escherichia coli RNase H and avian myeloblastosis virus RT
      are unable to cleave the HIV RNA-tRNALys complex. We refer to this unusual
      activity as RNase D. Two lines of evidence indicate that the specific RNase D
      activity is an integral part of recombinant HIV RT. The specific RNase D activity
      comigrates with the other RT activities, DNA polymerase, and RNase H upon
      filtration on a Superose 6 gel column or chromatography on a phosphocellulose
      column. Moreover, three recombinant HIV-1 RT preparations expressed and purified
      in different laboratories by various procedures exhibit RNase D activity.
      Sequence analysis indicated that RNase D activity cleaves the substrate HIV-1 RNA
      tRNALys at two distinct sites within the PBS sequence 5'-UGGCGCCCGA decreases
      ACAG decreases GGAC-3'. The sequence specificity of RNase D activity suggests
      that it might be involved in two stages during the reverse transcription process:
      displacement of the PBS to enable copying of tRNALys sequences into plus-strand
      DNA or to facilitate the second template switch, which was postulated to occur at
      the PBS sequence.

PMID- 1371015
TI  - Intrinsic mechanisms involved in the electrophysiological properties of the
      vasopressin-releasing neurons of the hypothalamus.

PMID- 1371016
TI  - Calcium-independent release of amino acid neurotransmitters: fact or artifact?

PMID- 1371017
TI  - Regulation of adenylyl cyclase from Paramecium by an intrinsic potassium
      conductance.
AB  - Hyperpolarization of the cell membrane of Paramecium stimulates adenosine 3',5'
      monophosphate (cAMP) formation. Manipulations of the K+ resting conductance of
      the ciliate by adaptation in different buffers affected excitability of the cAMP
      generating system. Blockade of K+ channels inhibited hyperpolarization-stimulated
      cAMP formation. A mutant of Paramecium that is unable to control its K+ resting
      conductance had a defect in cAMP formation. Purified adenylyl cyclase, when
      incorporated into an artificial lipid bilayer membrane, revealed properties of a
      voltage-independent K+ channel. This indicates that the adenylyl cyclase of
      Paramecium has a secondary function as carrier of the K+ resting conductance. A
      hyperpolarization-activated K+ efflux appears to directly regulate adenylyl
      cyclase activity in vivo.

PMID- 1371018
TI  - Treatment of myelodysplastic syndromes with hemopoietic growth factors.

PMID- 1371019
TI  - Differentiation-inducing agents in the treatment of myelodysplastic syndromes.

PMID- 1371020
TI  - [Acute urinary obstruction].
AB  - Acute urinary obstruction is a painful occurrence well known to every physician.
      It is a matter of a reflexogenic closure of the bladder neck. As the nerves,
      regulating the neck as well as the motoricity of the bladder, extend directly
      over the capsule of the prostate, functional disorders during growth of the
      prostate are possible at any time, independent of the prostatic volume. Since in
      case of prostatic hyperplasia the smooth muscles of the bladder neck are partly
      transformed into fibrous tissue, drug treatment in case of acute urinary
      obstruction is impossible. Therefore catheterisation is applied now as before.

PMID- 1371021
TI  - [Ultrasonography of the prostate].
AB  - Suprapubic sonography of the prostate is a comfortable and painless examination
      which requires not much effort and yields the relevant information about size,
      form and residual urine for the daily clinical routine. For the assessment of the
      echo structure, particularly in case of carcinoma of the prostate, transrectal
      sonography is superior to suprapubic examination. However, transrectal ultrasound
      examination in case of prostatic carcinoma or suspicion of prostatic carcinoma is
      not often indicated, since in the majority of the cases the diagnosis as well as
      the therapeutic concept can be clearly determined, based on rectal palpation,
      determination of prostate specific antigen (PSA) and prostatic biopsy. As
      screening investigation in the early diagnosis of prostatic carcinomas,
      transrectal sonography is an inappropriate measure due to poor sensibility as
      well as specificity.

PMID- 1371022
TI  - Comparison of Bay K 8644, nitrendipine and atropine on spontaneous and pelvic
      nerve-induced bladder contractions on rat bladder in vivo.
AB  - The effects of the dihydropyridine-type calcium antagonist (nitrendipine) and
      agonist (Bay K 8644) in comparison to atropine have been studied after
      intravenous administration on spontaneous and pelvic-nerve-induced contraction of
      rat urinary bladder. Bay K 8644 increased the basal internal bladder pressure as
      well as the amplitude of the spontaneous bladder contractions in a dose-dependent
      manner. In addition, an increase in systemic arterial blood pressure was noted
      for a period of about 20 min. In the presence of atropine the effects of Bay K
      8644 on the urinary bladder were almost completely antagonized. Both nitrendipine
      and atropine reduced in a dose-dependent manner the amplitude of spontaneous and
      nerve-induced bladder contraction. The spontaneous and nerve-induced bladder
      contractions were significantly reduced by atropine or nitrendipine. Only
      nitrendipine caused a reduction of the spontaneous bladder contraction frequency.
      The systemic blood pressure was decreased significantly by nitrendipine but not
      after atropine administration. We suggest that both calcium antagonist and
      agonist can change the tension of the urinary bladder in vivo. As a side-effect
      the systemic blood pressure is altered. Atropine can antagonize the effect of
      BayK 8644 on the urinary bladder and reduces spontaneous and nerve-induced
      bladder contractions more specifically than nitrendipine.

PMID- 1371023
TI  - Receptor function studies in specimens from the proximal human urethra obtained
      by transurethral resection.
AB  - During transurethral resection (TUR) for prostatic hyperplasia, specimens were
      taken from the proximal urethra. Muscle strips thus obtained were mounted in an
      organ bath and muscle contraction was induced by adding increasing concentrations
      of noradrenaline (NA), methoxamine (alpha 1-agonist) and clonidine (alpha 2
      agonist). NA and methoxamine induced a dose-dependent muscle contraction, but
      clonidine had no effect. The influence of prazosin (alpha 1-antagonist) and
      yohimbine (alpha 2-antagonist) on the NA-induced muscle contraction was also
      evaluated. Both antagonists had an inhibitory effect, which was much more potent
      with prazosin. The specimens taken during TUR were found to be suitable for in
      vitro receptor function studies. The alpha-adrenergic receptor function in the
      proximal human urethra was found to be mainly of the alpha-type.

PMID- 1371024
TI  - Fine specificity of the B-cell epitopes recognized in HIV-1 NEF by human sera.
AB  - We have previously used partially overlapping synthetic nonapeptides to
      characterize the human natural antibody response against HIV-1 negative
      regulatory factor (NEF), and identified nine 5 to 13 amino acid long regions that
      were recognized by sera of HIV-1-infected individuals. In this report we define
      the minimal size of these epitopes with the use of shorter, from 3 to 8 amino
      acid long partially overlapping peptides covering the complete sequence of the
      previously identified reacting regions and the N- and C-terminal flanking
      sequences. We also introduce a new method for the analysis of the reactivities
      obtained with peptides of different lengths. In six of the antigenic regions the
      epitopes were found to be noncontiguous and to consist of multiple, down to three
      amino acid long separate reactive stretches (epitope 1: WSK, VGW, TVRERMRR;
      epitope 3A: PLRPM, SHFLK; epitope 3B: SQRRQD, DLW; epitope 3C: IYHT, QGYFPDWQN;
      epitope 4: SLL, VSL; epitope 5: EVLEWRFDSR, VAR). Three epitopes were clearly
      linear (epitope 2: CAWLE; epitope 3D: LTFGWC; epitope 6: PEYF). Interestingly,
      five of the minimized B-cell epitopes (1, 3A, 3C, 3D, 5) recognized by human sera
      overlap totally or partly with the previously identified T-cell epitopes in HIV-1
      NEF. Also, only three of the epitopes (3C, 3D, 5) were in a computer-based
      homology search shown to contain strictly NEF-specific sequences.

PMID- 1371025
TI  - Neutralizing epitopes on herpes simplex virus-1-expressed rotavirus VP7 are
      dependent on coexpression of other rotavirus proteins.
AB  - We constructed a recombinant thymidine kinase-negative herpes simplex virus type
      1 (HSV-1) that expressed the rotavirus major outer capsid glycoprotein, VP7. In
      the recombinant HSV-1, a promoter from the 5' noncoding region of the HSV-1
      glycoprotein B locus regulated the expression of VP7 as a HSV-1 gamma 1 gene
      product. HSV-1-expressed VP7 resembled rotavirus-expressed VP7 in its SDS-PAGE
      mobility, high mannose-type glycosylation, disulfide bonding, perinuclear to
      cytoplasmic localization, intracellular retention, and reactivity with polyclonal
      antisera and nonneutralizing antibodies. Unlike rotavirus-expressed VP7, HSV-1
      expressed VP7 lacked several neutralizing epitopes by immuno-histochemical
      staining and by ELISA. One neutralizing epitope identified on HSV-1-expressed VP7
      by ELISA was masked by paraformaldehyde fixation of recombinant HSV-1- but not
      rotavirus-infected cells. Neutralizing epitopes were restored to HSV-1-expressed
      VP7 by coinfection of cells with the HSV-1 recombinant and a heterologous
      rotavirus that lack the neutralizing epitopes. The recovered neutralizing
      epitopes were detected on double-shelled rotavirus particles produced in the
      coinfected cells. This study indicates that the formation of several neutralizing
      epitopes on rotavirus VP7 requires interaction of VP7 with other rotavirus
      proteins. In addition, HSV-1 was a useful vector for studying the localization,
      processing, and antigenicity of an RNA virus glycoprotein.

PMID- 1371026
TI  - Characterization of a major neutralization domain of Ross river virus using anti
      viral and anti-peptide antibodies.
AB  - The E2 glycoprotein of the alphavirus Ross River virus (RRV) contains three
      defined neutralization epitopes (a, b1 and b2) with determinants located between
      amino acids 216 and 251 in the linear sequence (Vrati et al., 1988, Virology 162,
      346-353). The antigenic structure of this region has been examined using
      hyperimmune mouse antiserum against RRV and antiserum against four synthetic
      peptides representing linear amino acid sequences in the neutralization region of
      E2. In plaque reduction neutralization tests using hyperimmune antiserum to RRV,
      an RRV mutant altered at all three neutralization epitopes was markedly more
      resistant than the parental virus; variants altered at single epitopes could not
      be distinguished in these tests. Sera from mice immunized with synthetic RRV E2
      peptides conjugated to keyhole limpet haemocyanin reacted, in a direct ELISA,
      with the specific region of RRV represented by the peptide. The same sera did not
      neutralize or immunoprecipitate RRV in solution or bind to RRV in a capture
      ELISA. The RRV peptides did not prime mice to react to a subimmunogenic dose of
      RRV; they did not bind monoclonal or polyclonal antibodies to RRV. We conclude
      that a significant proportion of the neutralizing antibody response in mice is
      elicited by epitopes a, b1, and b2 of RRV E2 and that the sites to which
      neutralizing antibodies bind are formed by complex folding.

PMID- 1371027
TI  - Epitope-mapped monoclonal antibodies against the HPV16E1--E4 protein.
AB  - The human papillomavirus (HPV) E1--E4 protein is the only nonstructural late
      protein encoded by the virus. We have isolated three hybridomas producing
      monoclonal antibodies to the E1--E4 protein of HPV16, which is the HPV type most
      frequently associated with cervical cancer. The three antibodies (TVG 401, 402,
      and 403) detect adjacent epitopes within the major seroreactive region of the
      molecule and show no reactivity against the E4 proteins of HPV1, HPV2, HPV4, or
      HPV6. The E1--E4 protein migrates as a 10K species on SDS-gel electrophoresis and
      forms cytoplasmic inclusion granules in infected cells in vitro similar in
      appearance to those produced by HPV1 in benign warts. In naturally occurring
      HPV16-induced tumors the E1--E4 protein was detected in the cytoplasm of cells in
      the upper layers of the lesion in areas in which HPV16 DNA replication was
      occurring, as determined by in situ hybridization. Although the epitopes
      recognized by these monoclonal antibodies survive brief fixation in 5%
      formaldehyde, reactivity was destroyed by prolonged fixation. These monoclonal
      antibodies represent the first against HPV16 E1--E4 and should complement those
      already available to E7 and L1 for the screening of frozen sections of clinical
      biopsies and will be of value in monitoring the progression of HPV infection from
      benign lesions to invasive cancer.

PMID- 1371028
TI  - Localization of the antigenic sites and intrinsic protein kinase domain within a
      300 amino acid segment of the ribonucleotide reductase large subunit from herpes
      simplex virus type 2.
AB  - The 140-kDa ribonucleotide reductase (RR1) protein of herpes simplex virus type 2
      (HSV-2) functions as the large subunit of virus-specified RR1 and exhibits an
      intrinsic protein kinase (PK) activity at its unique NH2-terminal region. The N
      terminal half of RR1 contains the protein and DNA functions of the morphological
      transforming region III (mtrIII) of HSV-2. In the present study, we have
      expressed a number of truncated RR1 derivatives in a mammalian expression vector
      containing NH2-terminal RR1 gene fragments and amber mutants generated by site
      specific mutagenesis. These derivatives, synthesized in transient expression
      assays, were used as test antigens to localize the epitopes of a panel of HSV-2
      RR1-reactive monoclonal antibodies and to fine-map the PK catalytic domain. Our
      data show that the epitope for HSV-2-specific monoclonal antibody 6A-6 is located
      in a region of RR1 protein spanning aa 72-350. The epitopes for cross-reactive
      antibodies to HSV RR1, i.e., 48S and 51S, are formed predominantly by a stretch
      of amino acid residues specified by aa 350-376 of the RR1 molecule. The 6A-6
      antibody utilized in conjunction with the RR1 amber mutants has allowed us to
      define a 278 aa domain within the NH2-terminal half of the 140-kDa RR1 (aa 72
      350) that is sufficient for PK activity.

PMID- 1371029
TI  - Mechanism of inhibition of HIV-1 infection in vitro by purified extract of
      Prunella vulgaris.
AB  - Crude extracts of four Chinese herbs, Arctium lappa, Astragalus membranaceus,
      Andrographis paniculata, and Prunella vulgaris, were assessed in several tissue
      culture lines for anti-HIV activity and for cytotoxicity. One extract, obtained
      from P. vulgaris, was able to significantly inhibit HIV-1 replication with
      relatively low cytotoxicity. The active factor was purified using sequential
      precipitations with ethanol and n-butanol, followed by reverse-phase and gel
      permeation high-performance liquid chromatographic separations. The active
      component was anionic with a molecular weight of approximately 10 kDa. The
      purified extract inhibited HIV-1 replication in the lymphoid cell line MT-4, in
      the monocytoid cell line U937, and in peripheral blood mononuclear cells at
      effective concentrations of 6, 30, and 12.5 micrograms/ml, respectively.
      Pretreatment of uninfected cells with the extract prior to viral exposure did not
      prevent HIV-1 infection. By contrast, preincubation of HIV-1 with the purified
      extract dramatically decreased infectiousness. The purified extract was also able
      to block cell-to-cell transmission of HIV-1, prevented syncytium formation, and
      interfered with the ability of both HIV-1 and purified gp120 to bind to CD4. PCR
      analysis confirmed the absence of HIV-1 proviral DNA in cells exposed to virus in
      the presence of the extract. These results suggest that the purified extract
      antagonizes HIV-1 infection of susceptible cells by preventing viral attachment
      to the CD4 receptor.

PMID- 1371030
TI  - Activation of human immunodeficiency virus type 1 provirus in T-cells and
      macrophages is associated with induction of inducer-specific NF-kappa B binding
      proteins.
AB  - We have analyzed the limiting factors involved in the induction of human
      immunodeficiency virus type 1 (HIV-1) provirus expression by tumor necrosis
      factor-alpha (TNF-alpha), phorbol-12-myristate-13-acetate (PMA), and bryostatin-1
      in T-cells (ACH-2) and monocytes (U1). We have demonstrated that, while there is
      a correlation among the increase of 9.2-kilodalton (kDa) HIV-1 RNA, the increase
      of viral proteins (p24) in the cells, and the release of HIV-1 virions into the
      medium, there is no direct correlation between the levels of induced NF-kappa B
      binding proteins and the expression of HIV-1 provirus. The presence of nuclear NF
      kappa B-specific proteins appears to be essential only for the initiation of
      viral replication, since the HIV-1 transcripts could be detected in TNF-alpha or
      bryostatin-1-stimulated cells also at later times postinduction, times when no NF
      kappa B proteins could be detected in the nucleus. The uv crosslinking of DNA and
      proteins has shown that TNF-alpha, PMA, and bryostatin-1 induce different sets of
      NF-kappa B binding proteins with distinct kinetics of binding.

PMID- 1371031
TI  - Ontogenic differences in the nutritional regulation of circulating IGF binding
      proteins in sheep plasma.
AB  - Well-fed castrated male sheep (N = 3) and 125 days gestation pregnant ewes (N =
      6) with chronically catheterized fetuses were fasted for 72 h. Insulin-like
      growth factor-binding protein (IGFBP) levels in fed and starved fetal, maternal
      and castrated male sheep plasma were measured using ligand blot analysis. IGFBPs
      in adult and fetal sheep differed in distribution both before and after 72 h
      starvation. IGFBP-3 was the major postnatal binding protein, while in the fetus
      IGFBP-2, IGFBP-3 and the circulating IGF type 2 receptor fragment each
      contributed 25-30% of total IGF binding capacity. After starvation, total IGF
      binding capacity and IGFBP-3 fell in plasma of maternal and castrated male sheep
      (p less than 0.05). Total IGF binding capacity rose with starvation in fetal
      plasma (p less than 0.05) as a result of an increase in IGFBP-1 (p less than
      0.01) and IGFBP-2 (p less than 0.05). The different nutritional control of the
      IGFBPs in the fetus and the adult may reflect ontogenic differences in the
      regulation and function of circulating IGFs and their binding proteins.

PMID- 1371032
TI  - Functional expression of human myometrial endothelin receptors in Xenopus laevis
      oocytes.
AB  - We demonstrate the existence of functional endothelin receptors in human uterine
      myometrium using the Xenopus oocyte expression system. Fifty nanograms of
      poly(A)+RNA from myometrium was injected into Xenopus laevis oocytes and
      incubated for 70-80 h. The membrane potential of the oocyte was clamped at -60 mV
      and membrane current was measured during and after endothelin stimulation.
      Endothelin-1 elicited a large inward membrane current in the oocytes injected
      with poly(A)+RNA; endothelin-2 elicited a small current; while endothelin-3 did
      not induce any membrane current. These results indicate the existence of
      messenger RNA encoding functional endothelin-1 receptors in human uterine
      myometrium.

PMID- 1371033
TI  - Polarized efflux of iodide in porcine thyrocytes occurs via a cAMP-regulated
      iodide channel in the apical plasma membrane.
AB  - The intracellular regulation of thyrotropin-stimulated iodide efflux was studied
      in polarized porcine thyrocytes grown as a continuous, tight monolayer in
      bicameral culture chambers. From a previous study using this system we know that
      thyrotropin rapidly increases iodide efflux in the apical but not basal direction
      of the polarized epithelium. [125I]-iodide efflux in apical direction was
      stimulated by thyrotropin in a concentration-dependent manner (1-10 U/l), whereas
      efflux in basal direction was unchanged at any thyrotropin dose. Thyrotropin
      induced elevation of intracellular cAMP showed a corresponding concentration
      dependence. The selective stimulation of apical efflux by thyrotropin was evident
      also when re-uptake of iodide released in basal direction was blocked by
      perchlorate. The effect of thyrotropin on apical efflux was mimicked by 8-bromo
      cAMP and forskolin, whereas agents known to activate the
      Ca2+/phosphatidylinositol cascade (epidermal growth factor) and protein kinase C
      (phorbol ester) or increase cytosolic [Ca2+] (A23187) were inactive. We conclude
      that the selective stimulation by thyrotropin of apical iodide efflux,
      corresponding to efflux in luminal direction in intact follicles, occurs via cAMP
      regulated iodide channels present in the apical domain of the plasma membrane.

PMID- 1371034
TI  - Preservation of endothelium-dependent vasodilation in the spastic segment of the
      human epicardial coronary artery by substance P.
AB  - The objective of this study was to determine if endothelium-dependent
      vasodilation is preserved in the spastic segment of the epicardial coronary
      artery. Segmental responses of the coronary artery to substance P were examined
      by the use of a quantitative angiographic technique in 21 patients with variant
      angina. Coronary diameter at the basal state did not differ between the spastic
      and the nonspastic segments (2.3 +/- 0.2 mm, 2.3 +/- 0.4 mm, p greater than
      0.05). Changes in coronary diameter in response to substance P did not differ
      between segments with ergonovine-induced spasm and nonspastic segments. Maximal
      dilation averaged 27.1 +/- 9.5% in the spastic segment and 24.4 +/- 9.6% in the
      nonspastic segment (expressed as a percent increase over the value before drug
      administration). It appears that both the potential of the endothelium to release
      endothelium-dependent relaxing factor and the dilating response of the smooth
      muscle to endothelium-dependent relaxing factor are preserved, even in the
      spastic segment.

PMID- 1371035
TI  - Stimulation of coronary collateral growth: current developments in angiogenesis
      and future clinical applications.

PMID- 1371036
TI  - Frequency of ventricular ectopic activity in isolated systolic systemic
      hypertension.

PMID- 1371037
TI  - The validity of continuing developmental follow-up of high-risk infants to age 5
      years.
AB  - We conducted a study to determine whether performance on developmental tests at
      age 5 years could predict academic achievement at age 8 years. As part of a
      longitudinal developmental surveillance project, 179 children at risk due to
      perinatal complications who had passed developmental screening through age 2 1/2
      years and 50 comparison children underwent an extensive prekindergarten
      psychoeducational test battery at age 5 years and took the Iowa Tests of Basic
      Skills at age 8 years, if they had reached the third grade. The mean Iowa Tests
      of Basic Skills score was significantly lower for those children who were
      "flagged" on the prekindergarten psychoeducational test battery (t = 5.39).
      Preacademic, rather than developmental, items appeared to be the best predictors.
      However, the prekindergarten psychoeducational test battery correctly predicted
      low achievement or grade retention in only 58% of cases. Its sensitivity was 0.45
      and its specificity was 0.85. No significant difference was noted between group
      Iowa Tests of Basic Skills mean scores for the high-risk or comparison group.
      When low achievement and failure to reach the third grade were combined,
      prevalence of "failure" was higher for the high-risk group (31% vs 24%). The only
      perinatal variable predictive of low achievement was neonatal seizures. In
      summary, because the ability to predict future academic achievement at age 5
      years is limited, routine developmental testing for symptom-free preschool
      children is not warranted. High-risk infant follow-up programs should focus on
      the first several years of life.

PMID- 1371038
TI  - Mechanism of action of foscarnet against viral polymerases.
AB  - Foscarnet is a pyrophosphate analogue with activity against herpesviruses, human
      immunodeficiency virus (HIV), and other RNA and DNA viruses. Foscarnet and its
      analogues achieve their antiviral effects via inhibition of viral polymerases,
      with such inhibition not being dependent on activation or phosphorylation of the
      compounds by viral or cellular proteins. Current evidence indicates that
      foscarnet interferes with exchange of pyrophosphate from deoxynucleoside
      triphosphate during viral replication by binding to a site on the herpesvirus DNA
      polymerase or HIV reverse transcriptase. Reviewed herein are basic findings
      regarding the mechanism of action and antiviral activity of foscarnet and the
      related compound phosphonoacetic acid (PAA), as well as findings regarding
      potential mechanisms of viral resistance and interactions with other antiviral
      agents.

PMID- 1371039
TI  - Clinical pharmacology: foscarnet.
AB  - Foscarnet exerts its antiviral effects via reversible inhibition of viral
      polymerases. Pharmacodynamic data indicate that herpesvirus and human
      immunodeficiency virus replication is inhibited by therapeutically achievable
      concentrations of foscarnet; however, the concentrations of foscarnet required
      for such inhibition have been found to vary widely. Pharmacokinetic data indicate
      that foscarnet is eliminated via the renal route, undergoes negligible
      metabolism, and appears to be distributed widely from the circulation. However,
      the available data indicate that the pharmacokinetics of the drug varies among
      patients and within the individual patient, particularly with regard to plasma
      drug levels; furthermore, such factors as the intracellular kinetics of the drug
      have yet to be well characterized. It is thus difficult to formulate optimal
      dosing regimens on the basis of what is known of foscarnet pharmacodynamics and
      pharmacokinetics. Nevertheless, dosages that produce clear-cut therapeutic
      benefits without unacceptable toxicity have been identified in clinical trials of
      foscarnet in acquired immunodeficiency syndrome (AIDS) patients with
      cytomegalovirus (CMV) retinitis.

PMID- 1371040
TI  - In vitro effects of interleukin-2 and gamma globulin on immune dysfunction in a
      patient with severe mucocutaneous herpes simplex virus infection.
AB  - A previously healthy woman developed severe, recurrent mucocutaneous herpes
      simplex virus (HSV) infection at 21 years of age. Immunologic assessment over the
      past 2 years has revealed persistent T-cell and natural killer cell dysfunction
      despite normal numbers of these cells as measured by flow cytometry. We studied
      the effect of recombinant interleukin 2 (rIL-2) and gamma globulin on the
      patient's mononuclear cells in 18-hour 51Cr release assays using HSV-infected and
      uninfected target cells. Both gamma globulin and rIL-2 significantly enhanced
      target cell lysis of HSV-infected target cells (P less than .001), but did not
      increase lysis of uninfected target cells. Addition of the patient's serum had no
      effect on HSV-infected target cell lysis despite a high HSV IgG titer, indicating
      a possible specific abnormality in production of antibody-dependent cellular
      cytotoxicity antibody.

PMID- 1371041
TI  - Exercise-induced allergies: the role of histamine release.
AB  - Exercise is a physical cause of allergic reactions, including exercise-induced
      anaphylaxis (EIAna), exercise-induced urticaria (EIU), exercise-induced asthma
      (EIA), and exercise-induced rhinitis (EIR). Since its first description in 1979,
      EIAna has been reported with variable clinical manifestations, with exercise
      alone, and in combination with food ingestion. Elevated serum histamine levels
      and cutaneous mast cell degranulation have been noted. Exercise-induced urticaria
      appears as small, punctate lesions that differ from the classic coalescent type
      seen with EIAna. Variant forms of EIAna with cholinergic urticarial lesions
      manifesting systemic collapse and/or respiratory distress have been studied.
      Exercise-induced urticaria and cold-induced urticaria may cause elevated plasma
      histamine levels coincident with the onset of pruritus and hives. Theories
      accounting for EIA include respiratory heat loss, water loss, and mast cell
      activation. Although some studies have shown increased plasma histamine with EIA,
      others have not. Recently, bronchoalveolar lavage in atopic subjects with EIA has
      been evaluated preexercise and postexercise, with no significant differences in
      histamine or tryptase, suggesting a pathogenesis of EIA independent of the mast
      cell. Exercise-induced rhinitis, with varying degrees of rhinorrhea, congestion,
      and sneezing, has been increasingly recognized in athletes who run, cycle, and
      ski. Cold-air-induced rhinorrhea in laboratory challenges displays a mediator
      release pattern similar to that produced by allergen-induced nasal challenges.
      Therapeutically, H1 antihistamines are recommended for EIAna both as pretreatment
      and acute therapy. H1 antihistamines may be helpful in EIU, but are recommended
      for EIAna both as pretreatment and acute therapy.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1371042
TI  - Antiarrhythmic drugs: good for premature ventricular complexes but bad for
      patients?

PMID- 1371043
TI  - Endoprosthetic replacement for bony metastases.
AB  - A series of 38 patients with long bone metastases treated at the Birmingham Bone
      Tumour Treatment Service with resection of the metastatic lesion and replacement
      of the bone defect with an endoprosthesis was reviewed. The majority of cases had
      pathological fractures due to a massive destructive lesion. Two-thirds of the
      patients had a solitary metastasis. Metastases from hypernephroma and breast
      carcinoma accounted for the majority of cases. All the patients were
      independently mobile after the endoprosthetic replacement and were pain free. The
      average survival rate after the endoprosthetic replacement was 14.7 months and
      this varies with the primary tumour. The indications for endoprosthetic
      replacement for the treatment of long bone metastases are outlined and the
      results and complications are discussed. It is concluded that endoprosthetic
      replacement for bony metastases is an effective palliative procedure for a
      selected group of patients.

PMID- 1371045
TI  - [Clinical approach to infection in patients with hematologic malignancy].
AB  - Patients with hematologic malignancy are susceptible to infection because of the
      disease process and its treatment. Profoundly granulocytopenic patients are at
      increased risk of developing Pseudomonas aeruginosa bacteremia, often with a
      fatal outcome. Therapy with one or two anti-pseudomonal beta-lactam antibiotics
      and an aminoglycoside in combination that were effective in vitro against the
      infecting organism proved to be superior, by one-week survival, to therapy with
      either one in vitro effective beta-lactam or aminoglycoside or inadequate drugs.
      On the other hand, treatment with granulocyte colony-stimulating factor had no
      significant association with longer survival, although a favorable outcome was
      well correlated with an increase in the granulocyte count during therapy. An
      active mycobacteriosis was documented in 2% of all patients with hematologic
      malignancy. Dissemination occurred in half of them. The prognosis of tuberculosis
      was depended mainly on early diagnosis and treatment, while that for the atypical
      variety was largely influenced by the underlying disease. The frequency of deep
      fungal infection in patients with acute leukemia at autopsy increased
      progressively from 10% in 1970-1974 to 38% in 1983-1986, but it decreased
      somewhat to 29% in 1987-1989 after the introduction of empiric amphotericin B
      therapy in 1986. Early empiric antifungal therapy should therefore be started in
      granulocytopenic patients with fever refractory to antibacterial therapy, because
      of unreliability of the current serodiagnosis. A total protective isolation for
      patients undergoing bone marrow transplantation (BMT) was associated with a
      reduced incidence of pneumonia, especially due to Aspergillus, and to a lesser
      extent, bacteremia. Cytomegalovirus pneumonia complicating BMT continues to have
      a poor prognosis, although the frequency has gradually been decreasing with the
      introduction of effective preventive measures. An early diagnosis and treatment
      as well as preventive measures is thus necessary for infection control in
      patients with hematologic malignancy.

PMID- 1371044
TI  - Differential effects of human recombinant interferons on the expression of two
      early gene products of Epstein-Barr virus.
AB  - Two human Burkitt's lymphoma (BL) cell lines, Raji and Daudi, have been
      previously characterized as resistant and sensitive, respectively, to the anti
      Epstein-Barr virus (EBV) effects of human leukocyte interferon. These cells are
      equally susceptible to P3HR-1 EBV superinfection as determined by EBV early
      antigen (EA) expression. The cell lines were pretreated with human recombinant
      interferons alpha 2, beta, or gamma and subsequently superinfected with P3HR-1
      EBV. Their expression of two distinct EBV early gene products was evaluated by
      fluorescence microscopy. Monoclonal antibodies to the diffuse (EA-D) and
      restricted (EA-R) components of the EA complex were used to determine the number
      of cells expressing each of these antigens in the treated cell lines. As
      previously described with human leukocyte interferon, EA-D expression in Raji
      cells was relatively resistant to interferon-alpha 2 pretreatment. Also, EA-D
      expression in Daudi cells was relatively sensitive. However, interferon alpha 2
      pretreatment produced an opposite pattern with respect to the expression of EA-R
      in these two cell lines; Raji cells were sensitive and Daudi cells relatively
      resistant. Interferon beta had the most uniformly effective anti-EBV activity on
      both cell lines; less than 15 U/ml produced 50% inhibition of both antigens in
      both cell lines. EA-D expression in both cell lines was sensitive to interferon
      gamma pretreatment and EA-R was resistant. These data suggest that different gene
      products of EBV are independently regulated by interferons based on at least
      three factors: (1) the host cell, (2) the type of interferon and (3) the affected
      gene product.

PMID- 1371046
TI  - [Respiratory infections associated with lung cancer].
AB  - We have analyzed the clinical significance of secondary infections associated
      with lung cancer patients. The incidence of secondary infections was 51.4% in 214
      in-patients with lung cancer admitted to our institution in 1988 and 1989, and
      almost all of them had respiratory tract infections. The incidence was high in
      patients with cell types other than adenocarcinoma, and in those with
      hypoproteinemia, impaired cellular immunity and obstruction of the airway. The
      prognosis in patients with infection was much poorer than that in patients
      without infection. Major causative pathogens were Staphylococcus aureus including
      methicillin-resistant S. aureus (MRSA), Haemophilus influenzae, Klebsiella spp.
      and Pseudomonas aeruginosa. These pathogens except for H. influenzae were
      isolated at the terminal stage, in cases with airway obstruction and in post
      cancer-chemotherapeutic phase. The efficacy rate of 194 chemotherapeutic regimens
      against infection was 57.7%. Although the efficacy rate in 1988 and 1989 exceeded
      that in the 1970s, there was no significant difference in the efficacy rate
      between monotherapy (57.1%) and combined therapy (59.3%). The effectiveness was
      very poor for infections caused by P. aeruginosa and MRSA, or for cases with
      airway obstruction and marked impairment of pulmonary blood flow. The above
      results showed that a new combined therapy as well as the measures to improve the
      general condition of compromised hosts are required in the treatment of secondary
      infections in these patients.

PMID- 1371047
TI  - [High-dose thio-TEPA with escalating doses of epirubicin and autologous
      hematopoietic stem cell transplant for refractory cancers].
AB  - We studied high-dose chemotherapy with autologous hematopoietic stem cell
      transplant for patients (pts) with non-Hodgkin's lymphoma (NHL) and breast cancer
      (BC) refractory to conventional therapies. The conditioning regimen consisted of
      thio-TEPA 6 mg/kg/day for 3 consecutive days with escalating doses of epirubicin
      (EPI) in dose steps of 120, 150, 180 and 210 mg/m2 on day 1. Mucositis was dose
      limiting toxicity at 210 mg/m2 on this regimen, and the recommended dose of EPI
      was judged to be 180 mg/m2. No cardiotoxicities were observed. There were 3 with
      complete responses (CR), one partial response (PR) in pts with NHL, 3CR and 5PR
      in pts with BC. The median duration of response was 8 months (mos) and 4 mos,
      respectively. Hematological recovery was significantly earlier in the pts
      receiving both autologous bone marrow transplant (ABMT) and peripheral blood stem
      cell transplant (PBSCT) than ABMT alone. This approach made it possible to
      overcome the prolonged PLT recovery, which was one of the major problems on ABMT.

PMID- 1371048
TI  - [Fundamental study of subrenal capsule assay by measuring specific activity of
      succinate dehydrogenase].
AB  - It may not show accurate results if subrenal capsule assay (SRCA) is made only by
      measuring tumor size, because of infiltration of host inflammation cells resulted
      from host immune reaction. We developed a new method which make possible an
      accurate determination of chemosensitivity by measuring specific activity of
      succinate dehydrogenase (SD) of the tumor cells implanted in the subrenal
      capsular space. With reference to SDI test, the assay condition for measuring
      specific activity of SD was determined. A comparative study was carried out in
      which malignant tumors of the oral cavity serially transplanted in nude mice were
      tested with SRCA and subcutaneous transplantation assay in nude mice.
      Chemosensitivity to peplomycin (PEP), CDDP and 5-fluorouracil (5-FU) evaluated
      SSDI method and nude mouse assay showed a high correlation than those evaluated
      by TGIR method and nude mouse assay. The overall predictive accuracy compared
      with nude mouse assay was 72.2% by TGIR method and 88.9% by SSDI method. SSDI
      method seemed to be a useful method to evaluate the chemosensitivity in SRCA.

PMID- 1371049
TI  - [A case of diffuse large cell lymphoma treated with combination chemotherapy of
      CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) and BEMP
      (bleomycin, etoposide, mitoxantrone, procarbazine) with complete remission].
AB  - A 73-year-old man with diffuse large cell lymphoma was treated with noncross
      resistant alternating combination chemotherapy of CHOP and BEMP, consisting of
      cyclophosphamide (1,000 mg/body, i.v., day 1), doxorubicin (60 mg/body, i.v., day
      1), vincristine (2 mg/body, i.v., day 1), prednisolone (100 mg/body, p.o., day 1
      5), bleomycin (30 mg/body, i.v., day 22), etoposide (80 mg/body, i.v., day 22
      24), mitoxantrone (6 mg/body, i.v., day 22), and procarbazine (100 mg/body, p.o.,
      day 22-26). Following the three courses' administration of CHOP and BEMP,
      complete remission was obtained with a remission duration of over ten months.
      Leukocytopenia was a dose-limiting factor. It is concluded that noncross
      resistant alternating combination chemotherapy of CHOP and BEMP is effective for
      diffuse large cell lymphoma.

PMID- 1371051
TI  - Total RNA isolation by a rapid centrifugation method.

PMID- 1371050
TI  - Binding of transforming growth factor-beta 1 to methylamine-modified alpha 2
      macroglobulin and to binary and ternary alpha 2-macroglobulin-proteinase
      complexes.
AB  - The binding of 125I-labelled transforming growth factor-beta 1 (TGF-beta 1) to
      human alpha 2-macroglobulin (alpha 2M) was studied by native PAGE and
      autoradiography. TGF-beta 1 bound preferentially to alpha 2M-methylamine and
      minimally, if at all, to native alpha 2M. Preparations of alpha 2M-proteinase
      complex were generated by incubating a standard concentration of alpha 2M (0.4
      microM) with different concentrations of trypsin, chymotrypsin or neutrophil
      elastase (0.04-2.0 microM). The 125I-TGF-beta 1-binding activity depended on the
      initial ratio of active proteinase to alpha 2M, or r value, used to form the
      alpha 2M-proteinase complex. With all three proteinases, r values of 2 or greater
      yielded preparations with unchanged or decreased TGF-beta 1-binding activity
      relative to native alpha 2M. By contrast, r values near 1 yielded preparations
      with significantly increased TGF-beta 1-binding activity. The results of
      [3H]thymidine-incorporation studies performed in mouse keratinocytes were
      consistent with the 125I-TGF-beta-binding experiments. alpha 2M-trypsin and alpha
      2M-chymotrypsin prepared at an r value of 1.0 counteracted the activity of TGF
      beta 1, whereas the equivalent complexes prepared at an r value of 3.0 had no
      effect. As determined by SDS/PAGE, 125I-TGF-beta 1 binding to alpha 2M
      methylamine was at least 80% non-covalent. Reaction of alpha 2M-methylamine with
      iodoacetamide or 5,5'-dithiobis-(2-nitrobenzoic acid) decreased the percentage of
      covalent binding but had no effect on total binding. Neuraminidase treatment had
      no effect on the binding of 125I-TGF-beta 1 to alpha 2M-methylamine. Cleavage of
      the 'bait regions' in alpha 2M-methylamine by prolonged treatment with trypsin
      also had no effect. These studies suggest that TGF-beta 1 binding to alpha 2M is
      enhanced by conformational change in the proteinase inhibitor resulting from
      reaction with proteinase or amine. If both proteinase-binding sites in a single
      alpha 2M molecule are occupied, TGF-beta 1-binding activity is decreased or
      perhaps eliminated.

PMID- 1371052
TI  - Isolation of cDNA including a reverse transcriptase-like sequence transcribed
      from the long interspersed repetitive DNA sequence of rat.
AB  - The mammalian genome congains long interspersed repetitive sequences, but the
      role of these repetitive sequence is not clear. A cDNA clone has been isolated
      that contains part of the L1 sequences from a cDNA library of rat liver. The DNA
      sequence analysis showed the homology of cDNA to several reverse transcriptases.
      The homology between the amino acid sequences predicted from L1 consensus
      sequences and reverse transcriptases has been reported previously. However, this
      is the first isolation of a cDNA clone containing a reverse transcriptase-like
      sequence.

PMID- 1371053
TI  - Purification and properties of gamma-glutamyltranspeptidase from Bacillus
      subtilis (natto).
AB  - To understand the mechanism by which gamma-polyglutamic acid (gamma-PGA) in the
      sticky material of natto was synthesized, we purified the gamma
      glutamyltranspeptidase (gamma-GTP) (EC 2.3.2.2) from the culture broth of
      Bacillus subtilis (natto) to homogeneity. gamma-GTP was composed of two subunits
      with molecular weight of 45,000 and 22,000. The N-terminal amino acid sequence of
      light subunit was homologous with that of gamma-GTP from Escherichia coli. The
      optimum pH and temperature of activity were 8.5 and 60 degrees C. The enzyme was
      inactivated by incubation for 15 min at pH 8.0 and 55 degrees C, but little loss
      of the activity was detected at 40 degrees C. gamma-GTP used glutamine as a gamma
      glutamyl donor and acceptor for gamma-PGA synthesis. Dipeptides were better gamma
      glutamyl acceptors than free amino acids.

PMID- 1371054
TI  - A sensitive viral capture assay for detection of plasma viremia in HIV-infected
      individuals.
AB  - Human immunodeficiency virus was detected in the serum/plasma of individuals
      infected with human immunodeficiency virus (HIV) after capture of virions on
      microparticles coated with monoclonal antibodies to external and transmembrane
      proteins of HIV-1. We analyzed serial samples obtained from 6 individuals who
      seroconverted, 18 asymptomatic, and 12 AIDS patients. HIV-1 RNA was detected in
      all (29/29) seropositive samples and in 6 seronegative samples immediately
      preceding seroconversion. In contrast, HIV antigen was detected in 13/29 (45%) of
      seropositive samples. HIV-1 RNA was also detected in 3 antigen-negative samples
      from one individual 8-5 months prior to seroconversion and in one sample from
      another person 2 days before antigen positivity. The intensity of the polymerase
      chain reaction (PCR) signal paralleled the concentration of HIV antigen.
      Conversely, seropositive HIV antigen-negative samples gave a weaker PCR signal.
      HIV-1 RNA was detected in 10/18 (60%) samples from asymptomatic, HIV antigen
      negative, individuals and in 11/12 (92%) specimens obtained from AIDS patients.
      The viral capture method may provide a sensitive, specific, and semiquantitative
      means of detecting circulating HIV at all stages of infection.

PMID- 1371055
TI  - Severe hypersensitivity reactions among HIV-seropositive patients with
      tuberculosis treated with thioacetazone.

PMID- 1371056
TI  - Transfer of several phytopathogenic Pseudomonas species to Acidovorax as
      Acidovorax avenae subsp. avenae subsp. nov., comb. nov., Acidovorax avenae subsp.
      citrulli, Acidovorax avenae subsp. cattleyae, and Acidovorax konjaci.
AB  - DNA-rRNA hybridizations, DNA-DNA hybridizations, polyacrylamide gel
      electrophoresis of whole-cell proteins, and a numerical analysis of carbon
      assimilation tests were carried out to determine the relationships among the
      phylogenetically misnamed phytopathogenic taxa Pseudomonas avenae, Pseudomonas
      rubrilineans, "Pseudomonas setariae," Pseudomonas cattleyae, Pseudomonas
      pseudoalcaligenes subsp. citrulli, and Pseudomonas pseudoalcaligenes subsp.
      konjaci. These organisms are all members of the family Comamonadaceae, within
      which they constitute a separate rRNA branch. Only P. pseudoalcaligenes subsp.
      konjaci is situated on the lower part of this rRNA branch; all of the other taxa
      cluster very closely around the type strain of P. avenae. When they are compared
      phenotypically, all of the members of this rRNA branch can be differentiated from
      each other, and they are, as a group, most closely related to the genus
      Acidovorax. DNA-DNA hybridization experiments showed that these organisms
      constitute two genotypic groups. We propose that the generically misnamed
      phytopathogenic Pseudomonas species should be transferred to the genus Acidovorax
      as Acidovorax avenae and Acidovorax konjaci. Within Acidovorax avenae we
      distinguished the following three subspecies: Acidovorax avenae subsp. avenae,
      Acidovorax avenae subsp. cattleyae, and Acidovorax avenae subsp. citrulli.
      Emended descriptions of the new taxa are presented.

PMID- 1371057
TI  - Piscirickettsia salmonis gen. nov., sp. nov., the causative agent of an epizootic
      disease in salmonid fishes.
AB  - A novel intracellular pathogen morphologically similar to the ehrlichiae has been
      isolated in cell culture and identified as the cause of an epizootic disease of
      salmonid fish. Like the ehrlichiae, the salmonid pathogen, designated strain LF
      89, replicates within membrane-bound cytoplasmic vacuoles in host cells. This
      agent is the first with characteristics of this type to be isolated from a fish.
      Analysis of the LF-89 16S rRNA indicated that, unlike the ehrlichiae, LF-89 is a
      gamma proteobacterium distantly related to Coxiella burnetii and perhaps
      Wolbachia persica. A new genus and species (Piscirickettsia salmonis gen. nov.,
      sp. nov.) are proposed for this organism, with ATCC(R) VR 1361 as the type
      strain.

PMID- 1371058
TI  - Marine star-shaped-aggregate-forming bacteria: Agrobacterium atlanticum sp. nov.;
      Agrobacterium meteori sp. nov.; Agrobacterium ferrugineum sp. nov., nom. rev.;
      Agrobacterium gelatinovorum sp. nov., nom. rev.; and Agrobacterium stellulatum
      sp. nov., nom. rev.
AB  - Two new species of aerobic, gram-negative, peritrichously flagellated or
      nonmotile marine bacteria usually forming star-shaped aggregates were isolated
      from northeastern Atlantic Ocean bottom sediments. These organisms resembled
      eight star-shaped-aggregate-forming bacterial species from the Baltic Sea
      originally ascribed to the genus Agrobacterium but not included on the Approved
      Lists of Bacterial Names because of their questionable relationships to true
      agrobacteria. These two sets of star-shaped-aggregate-forming bacteria were
      compared by means of phenotypic data, DNA base compositions, DNA-DNA relatedness,
      and one-dimensional electrophoretic analysis of low-molecular-weight RNAs (5S
      rRNA and tRNA). According to the results of genotyping, the northeastern Atlantic
      Ocean isolates and three of the Baltic Sea species formed a group of closely
      related bacteria that could not be excluded from the genus Agrobacterium with
      certainty. Until more genotypic data are available, these five marine species are
      regarded as a distinct subdivision of the genus Agrobacterium consisting of
      Agrobacterium atlanticum sp. nov. (type strain, 1480T = DSM 5823T), A. meteori
      sp. nov. (type strain, 1513T = DSM 5824T), A. ferrugineum sp. nov. nom. rev.
      emend. (type strain, ATCC 25652T), A. gelatinovorum sp. nov. nom. rev. emend.
      (type strain, ATCC 25655T), and A. stellulatum sp. nov. nom. rev. emend. (type
      strain, ATCC 15215T). "A. aggregatum" proved to be a later subjective synonym of
      A. stellulatum, which had priority. The remaining four Baltic Sea species, "A.
      agile," "A. kieliense," "A. luteum," and "A. sanguineum," could not be placed in
      the new subdivision of Agrobacterium.

PMID- 1371059
TI  - Taxonomic status of Kitasatosporia, and proposed unification with Streptomyces on
      the basis of phenotypic and 16S rRNA analysis and emendation of Streptomyces
      Waksman and Henrici 1943, 339AL.
AB  - Species classified within the genus Kitasatosporia share many of the phenotypic
      characteristics typical of streptomycetes. By using a probabilistic
      identification scheme, they were identified with Streptomyces exfoliatus cluster
      5, a species group within Streptomyces. The four species studied hybridized with
      a 16S rRNA genus probe for Streptomyces spp., indicating a close relationship
      between the two genera. The kitasatosporias were resistant to selected polyvalent
      streptomycete phages tested. Quantitative analysis showed that meso
      diaminopimelic acid varied from 49 to 89% in Kitasatosporia species and from 1 to
      16% in Streptomyces species depending on growth conditions. On the basis of 16S
      rRNA analysis, it is proposed to reduce Kitasatosporia to synonymy with
      Streptomyces. As a result, the new names proposed are Streptomyces mediocidicus
      comb. nov., Streptomyces phosalacineus comb. nov., Streptomyces setae comb. nov.,
      and Streptomyces griseolosporeus comb. nov., nom. nov.

PMID- 1371060
TI  - Phylogenetic evidence for the transfer of Eubacterium suis to the genus
      Actinomyces as Actinomyces suis comb. nov.
AB  - The 16S rRNA primary structures of Eubacterium suis DSM 20639T (T = type strain)
      and Bifidobacterium bifidum DSM 20456T were determined by sequencing in vitro
      amplified rDNA. Sequence comparisons indicated that B. bifidum is moderately
      related to representatives of the genera Actinomyces and Mobiluncus. The closest
      relative of E. suis is Actinomyces pyogenes. E. suis and A. pyogenes are more
      closely related phylogenetically to one another than to the other Actinomyces
      species that have been investigated by using comparative 16S rRNA analysis.
      Therefore, we propose that E. suis should be transferred to the genus Actinomyces
      as Actinomyces suis comb. nov.

PMID- 1371061
TI  - How close is close: 16S rRNA sequence identity may not be sufficient to guarantee
      species identity.
AB  - 16S rRNA (genes coding for rRNA) sequence comparisons were conducted with the
      following three psychrophilic strains: Bacillus globisporus W25T (T = type
      strain) and Bacillus psychrophilus W16AT, and W5. These strains exhibited more
      than 99.5% sequence identity and within experimental uncertainty could be
      regarded as identical. Their close taxonomic relationship was further documented
      by phenotypic similarities. In contrast, previously published DNA-DNA
      hybridization results have convincingly established that these strains do not
      belong to the same species if current standards are used. These results emphasize
      the important point that effective identity of 16S rRNA sequences is not
      necessarily a sufficient criterion to guarantee species identity. Thus, although
      16S rRNA sequences can be used routinely to distinguish and establish
      relationships between genera and well-resolved species, very recently diverged
      species may not be recognizable.

PMID- 1371062
TI  - Identification of xenobiotic-degrading isolates from the beta subclass of the
      Proteobacteria by a polyphasic approach including 16S rRNA partial sequencing.
AB  - Nineteen gram-negative, aerobic, biodegradative isolates were identified by using
      a polyphasic taxonomic approach. The presence of the specific polyamine 2
      hydroxyputrescine and the presence of a ubiquinone with eight isoprenoid units in
      the side chain (ubiquinone Q-8) allowed allocation of these organisms to the beta
      subclass of the Proteobacteria. On the basis of the results of additional
      characterization experiments (i.e., API 20NE tests, determinations of soluble
      protein patterns, and DNA-DNA hybridization experiments), we classified six
      isolates as either Comamonas testosteroni, Comamonas acidovorans, or Alcaligenes
      xylosoxidans subsp. denitrificans. By using the same criteria we allocated two
      additional isolates to the genus Alcaligenes. A comparison of a 16S rRNA fragment
      (positions 1220 to 1377; Escherichia coli nomenclature) indicated that the
      remaining isolates should be allocated as follows: one is a member of C.
      testosteroni and one is a member of Acidovorax facilis, as confirmed by the
      results of additional DNA-DNA hybridizations; two others probably belong to the
      family Alcaligenaceae; six are related to "Alcaligenes eutrophus"; and one,
      strain NRRL 12228, occupies an isolated position.

PMID- 1371063
TI  - Reinterpretation of the taxonomic position of Xanthomonas maltophilia and
      taxonomic criteria in this genus. Request for an opinion.
AB  - The inclusion of "Pseudomonas maltophilia" Hugh 1981 in the genus Xanthomonas as
      Xanthomonas maltophilia (Hugh 1981) Swings et al. 1983 is questioned in view of
      the significant differences between these two taxa. This reclassification is not
      acceptable if practical means of differentiation in this genus are considered.
      The proposed alteration of the description of the genus Xanthomonas is also
      questionable because of the implications for everyday phytobacteriology. In view
      of the natural similarities, as well as the profound differences, between X.
      maltophilia and the genus Xanthomonas, we propose that a new genus should be
      created for X. maltophilia, which could be placed together with the genus
      Xanthomonas in a separate natural group.

PMID- 1371064
TI  - Towards a phylogeny of the genus Vibrio based on 16S rRNA sequences.
AB  - The inter- and intrageneric relationships of the genus Vibrio were investigated
      by performing a comparative analysis of the 16S rRNAs of 10 species, including
      four pathogenic representatives. The results of immunological and 5S rRNA studies
      were confirmed in that the genus is a neighboring taxon of the family
      Enterobacteriaceae. With regard to the intrageneric structure, Vibrio
      alginolyticus, Vibrio campbellii, Vibrio natriegens, Vibrio harveyi, Vibrio
      proteolyticus, Vibrio parahaemolyticus, and Vibrio vulnificus form the core of
      the genus, while Vibrio (Listonella) anguillarum, Vibrio diazotrophicus, and
      Vibrio hollisae are placed on the outskirts of the genus. Variable regions around
      positions 80, 180, and 450 could be used as target sites for genus- and species
      specific oligonucleotide probes and polymerase chain reaction primers to be used
      in molecular identification.

PMID- 1371066
TI  - Phylogeny of fast-growing soybean-nodulating rhizobia support synonymy of
      Sinorhizobium and Rhizobium and assignment to Rhizobium fredii.
AB  - We determined the sequences for a 260-base segment amplified by the polymerase
      chain reaction (corresponding to positions 44 to 337 in the Escherichia coli 16S
      rRNA sequence) from seven strains of fast-growing soybean-nodulating rhizobia
      (including the type strains of Rhizobium fredii chemovar fredii, Rhizobium fredii
      chemovar siensis, Sinorhizobium fredii, and Sinorhizobium xinjiangensis) and
      broad-host-range Rhizobium sp. strain NGR 234. These sequences were compared with
      the corresponding previously published sequences of Rhizobium leguminosarum,
      Rhizobium meliloti, Agrobacterium tumefaciens, Azorhizobium caulinodans, and
      Bradyrhizobium japonicum. All of the sequences of the fast-growing soybean
      rhizobia, including strain NGR 234, were identical to the sequence of R. meliloti
      and similar to the sequence of R. leguminosarum. These results are discussed in
      relation to previous findings; we concluded that the fast-growing soybean
      nodulating rhizobia belong in the genus Rhizobium and should be called Rhizobium
      fredii.

PMID- 1371065
TI  - Phylogenetic analysis of Alloiococcus otitis gen. nov., sp. nov., an organism
      from human middle ear fluid.
AB  - The partial 16S rRNA sequence of an unknown bacterium that was originally
      isolated from middle ear fluids of children with persistent otitis media was
      determined by reverse transcription. A comparison of this sequence with sequences
      from other gram-positive species having low guanine-plus-cytosine contents
      revealed that this bacterium represents a new line of descent, for which the name
      Alloiococcus otitis gen. nov., sp. nov., is proposed. The type strain is strain
      NCFB 2890.

PMID- 1371067
TI  - Staphylococcus muscae, a new species isolated from flies.
AB  - A new coagulase-negative species of the genus Staphylococcus, Staphylococcus
      muscae, is described on the basis of the results of a study of four strains that
      were isolated from flies. 16S rRNA sequences of the type strains of S. muscae,
      Staphylococcus schleiferi, and Staphylococcus sciuri were determined and used,
      together with the corresponding sequences of Staphylococcus aureus and
      Staphylococcus epidermidis, for a comparative analysis. The new species is
      characterized taxonomically; this species is differentiated from the other
      novobiocin-susceptible staphylococci by its physiological and biochemical
      activities, cell wall composition, and levels of genetic relatedness. The type
      strain of this species is strain MB4 (= CCM 4175).

PMID- 1371068
TI  - The use of discriminant analysis to guide palliative treatment for lung cancer
      patients.
AB  - The aim of this study was to develop a prognostic index for patients with
      inoperable non-small cell lung cancer which could predict survival to 3 months.
      This would enable less radiation dose to be given to patients where prognosis is
      limited by occult metastases, giving rise to less treatment morbidity and raising
      the therapeutic ratio. Data on 18 known prognostic factors were collected on 96
      patients. Performance status, lymphocyte count, weight loss and extent of disease
      were the most predictive factors and were combined into an index. Logistic
      discriminant analysis was employed to give a numerical score of likelihood of
      survival to 3 months, ranging from 0 (not likely) to 1 (certain). In this first
      set of 96 patients, 16 deaths were observed before 3 months, of which 6 were
      predicted. There was one false positive prediction. Overall accuracy of
      prediction was therefore 89% with 99% specificity. The same 4 prognostic factors
      were measured on a second set of 80 patients. Nineteen died before 3 months, of
      which 5 were predicted with 2 false positives, giving an overall accuracy of 80%
      and 97% specificity. A probability of survival of less than or equal to 0.2,
      although highly specific, was only applicable to 9% of patients and this was the
      limiting factor in the clinical usefulness of the test. A 16-branch tree diagram
      allows any patient to be assigned a risk factor based on the four predictive
      factors at the first clinic attendance. Use of the index could encourage more
      rational prescribing of radiation dose.

PMID- 1371069
TI  - Factors affecting treatment patterns of radiation oncologists in the United
      States in the palliative treatment of cancer.
AB  - A questionnaire was sent to 488 radiation oncologists in the United States and
      268 replied. Each was given a brief account of three hypothetical patients (one
      with brain metastases, one with locally advanced lung cancer and one with bone
      metastases) and asked how they would approach the problems posed. Younger
      radiation oncologists (less than 46 years) treated patients with brain metastases
      with a smaller number of fractions and were more likely to view the case of
      locally advanced lung cancer as palliative. The aim of the radiation oncologist
      was related to the treatment pattern chosen, with the aim to extend life
      frequently related to higher total dose and number of fractions. When the amount
      of private funding was compared with dose, number of treatments, and whether the
      case was called palliative or not, no relationship was found.

PMID- 1371070
TI  - The observed inhibitory potency of 3'-azido-3'-deoxythymidine 5'-triphosphate for
      HIV-1 reverse transcriptase depends on the length of the poly(rA) region of the
      template.
AB  - The inhibitory potency of 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP)
      against HIV-1 reverse transcriptase (HIV-1 RT) has been further evaluated. The
      results indicate that the previously reported low Ki values for AZTTP against HIV
      1 RT (2.35 nM) are due neither to the to the direct tight binding of AZTTP to HIV
      1 RT nor to the interaction of the enzyme with AZTMP moiety terminated primer
      templates, but instead they are an artifact of the use of a homotemplate-primer
      [poly(rA).oligo(dT)]. With a set of RNAs of defined sequence as templates, we
      demonstrate that the observed Ki value for AZTTP depends on the length of the
      poly(rA) region following the primer in the RNA template. The more adenosyl
      residues in the RNA template that are available for processive incorporation of
      TMP moieties, the lower is the observed Ki value for AZTTP. Since the potencies
      of new inhibitors of HIV-1 RT are usually compared with that for AZTTP, these
      results have important consequences for the process of discovery of new HIV
      inhibitors that are of potential use in AIDS therapy.

PMID- 1371071
TI  - NMR analysis of helix I from the 5S RNA of Escherichia coli.
AB  - The structure of helix I of the 5S rRNA from Escherichia coli has been determined
      using a nucleolytic digest fragment of the intact molecule. The fragment
      analyzed, which corresponds to bases (-1)-11 and 108-120 of intact 5S rRNA,
      contains a G-U pair and has unpaired bases at its termini. Its proton resonances
      were assigned by two-dimensional NMR methods, and both NOE distance and coupling
      constant information have been used to calculate structural models for it using
      the full relaxation matrix algorithm of the molecular dynamics program XPLOR.
      Helix I has A-type helical geometry, as expected. Its most striking departure
      from regular helical geometry occurs at its G-U, which stacks on the base pair to
      the 5' side of its G but not on the base pair to its 3' side. This stacking
      pattern maximizes interstrand guanine-guanine interactions and explains why the G
      U in question fails to give imino proton NOE's to the base pair to 5' side of its
      G. These results are consistent with the crystal structures that have been
      obtained for wobble base pairs in tRNAPhe [Mizuno, H., & Sundaralingam, M. (1978)
      Nucleic Acids Res. 5, 4451-4461] and A-form DNA [Rabbinovich, D., Haran, T.,
      Eisenstein, M., & Shakked, Z. (1988) J. Mol. Biol. 200, 151-161]. The
      conformations of the terminal residues of helix I, which corresponds to bases (
      1)-11 and 108-120 of native 5S RNA, are less well-determined, and their sugar
      puckers are intermediate between C2' and C3'-endo, on average.

PMID- 1371072
TI  - Type-specific antibodies to the platelet-derived growth factor receptors: role in
      elucidating the structural and functional characteristics of receptor types.
AB  - Two types of platelet-derived growth factor receptors have been cloned and
      sequenced. Both are glycoproteins with similar molecular weights. We have earlier
      established the ligand binding specificity, ligand-induced dimerization, and
      kinase activation of these two receptor types [Bishayee et al. (1989) J. Biol.
      Chem. 264, 11699-11705; Kanakaraj et al. (1991) Biochemistry 30, 1761-1767]. In
      the present studies, we have investigated the biosynthesis, processing, and
      glycosylation of the alpha-receptor and compared its structural and functional
      characteristics to those of the beta-receptor. Unlike an anti-peptide antibody,
      AbP2 (amino acid residues 964-979), to the human beta-receptor which detects a
      phosphorylation-specific conformation of the receptor, an antibody, AbP alpha 2
      (amino acid residues 956-971), to the corresponding region of the human alpha
      receptor failed to do so. However, our studies revealed that the stability of the
      alpha-receptor is comparable to that of the beta-receptor. In addition, N-linked
      glycosylation of the alpha-receptor, like that of the beta-receptor, is not
      important in kinase activation. We have exploited the lack of an effect of N
      linked oligosaccharides on the functioning of the alpha-receptor to develop a
      simple and rapid method for direct demonstration of ligand-induced noncovalently
      linked alpha-beta-receptor heterodimer formation. This method is based on the
      interaction between functionally active short and the long forms of two receptor
      types which can be resolved by denaturing gel electrophoresis.

PMID- 1371073
TI  - Segment spanning residues 727-768 of the complement C3 sequence contains a
      neoantigenic site and accommodates the binding of CR1, factor H, and factor B.
AB  - CR1, CR2, DAF, MCP, factor H, C4bp, factor B, and C3 are members of a family of
      structurally related molecules, the majority of which belong to the complement
      system. Several of these molecules also share functional features such as
      cofactor and decay/dissociation activity and compete with one another in binding
      to C3b. Since factor H appears to bind to multiple sites in C3, we investigated
      the relationship between the factor H- and CR1-binding sites in C3b. Factor H
      binding to C3b is inhibited by either the C3c or C3d fragments, and addition of
      both fragments together augments this inhibition. One monoclonal anti-C3c
      antibody, anti-C3-9, which recognizes a neoantigenic epitope expressed upon
      cleavage to C3 to C3b, inhibited both factor H and CR1 binding to EC3b cells.
      This monoclonal antibody (MoAb) also inhibited factor B binding to EC3b. Two
      observations further supported our hypothesis that these molecules bind to
      proximal sites in C3b. First, a synthetic peptide spanning this region of C3b
      (C3(727-768)) inhibited factor H binding. Second, antibodies raised against this
      peptide inhibited binding to CR1, factor H, and factor B to C3b. These data show
      that H binds to at least two sites in C3b: the site in the C3c fragment is within
      the identified CR1-binding domain while the site in the C3d fragment surrounds
      the CR2-binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371074
TI  - Purification and partial characterization of two types of growth-inhibitory
      protein latently present in rabbit serum.
AB  - Normal rabbit serum contained two kinds of growth-inhibitory protein, GI-I and GI
      II, in latent forms. These latent inhibitors were activated by incubation at 37
      degrees C for 12 h, and their activation was lowered by inhibitors for serine,
      cysteine and metalloproteinases. Both growth inhibitors were highly purified in
      active forms by successive column chromatographies. GI-I showed a major protein
      band with an Mr of 18,000 on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, while GI-II showed a major protein band with an Mr of 36,000. GI
      I and GI-II half-inhibited the growth of rat tumorigenic cell line (RSV-BRL) at
      concentrations of 0.5 ng/ml and 10 ng/ml, excess concentrations. Of the 15 cell
      lines tested, GI-I specifically inhibited the growth of rodent and lagomorph
      cells, whereas GI-II nonspecifically inhibited the growth of all cell lines
      tested. Specificities for cell type and malignancy were not observed with either
      inhibitor. These growth inhibitors were stable to a reducing reagent and
      proteinase inhibitors, but labile to urea, acid, organic solvents, trypsin,
      plasmin and heating at 95 degrees C for 5 min. These properties suggested that
      both growth inhibitors might be distinct from known growth-inhibitory factors.

PMID- 1371075
TI  - Molecular interaction between HIV-1 major envelope glycoprotein and dextran
      sulfate.
AB  - We investigated at the molecular level the interaction between, HIV-1 recombinant
      gp160 (rgp160) and low-molecular-weight dextran sulfate. We demonstrate the
      occurrence of a specific interaction between rgp160 and sulfated dextran beads,
      which is saturable, pH-dependent and inhibitable by soluble dextran sulfate but
      not by soluble dextran. This specific interaction has a low affinity, with an
      estimated Kd in the 10(-4) M range. In addition, the binding of rgp160 to soluble
      recombinant CD4 (sT4) can only be inhibited by the preincubation of rgp160, but
      not of sT4, with dextran sulfate. Taken together, these results demonstrate the
      occurrence of a low affinity, but specific interaction between dextran sulfate
      and rgp160. This may account, at least in part, for the anti-HIV-1 activity of
      dextran sulfate.

PMID- 1371076
TI  - CSF amine metabolites in depression.
AB  - The amine metabolites, namely homovanillic acid (HVA) and 5-hydroxy indoleacetic
      acid (5-HIAA) were measured in cerebrospinal fluid (CSF) of depressives (n = 30)
      and controls (n = 30). Depressed patients had significantly lower HVA levels than
      controls. No significant differences were noted between the two groups in 5-HIAA
      levels. However, the differences between the groups for the CSF HVA/5-HIAA ratio
      were larger than those for the CSF HVA alone (p less than 0.01 versus p less than
      0.025, respectively). HVA levels correlated positively with monoamine oxidase
      activity and adenosine deaminase activity.

PMID- 1371078
TI  - Clonal analysis of bcr-abl rearrangement in T lymphocytes from patients with
      chronic myelogenous leukemia.
AB  - The cytogenetic hallmark of chronic myelogenous leukemia (CML) is the
      Philadelphia chromosome (Ph1), which reflects a chromosomal translocation t(9;22)
      and a rearrangement of the ABL and bcr genes. This marker is found in all cells
      arising from the same malignant precursor cell and can be detected in CML cells
      of the myeloid, monocytic, erythroid, and B-lymphocyte lineage. It is, however,
      controversial as to whether T lymphocytes of CML patients carry this gene
      rearrangement. An answer to this question would clarify whether the translocation
      in CML occurs in a pluripotent hematopoietic stem cell or in a precursor cell
      already committed to certain lineages, but not the T-cell lineage. To address
      this question, we established T-cell clones from peripheral venous blood cells of
      four patients with CML and screened these clones for bcr-abl fusion transcripts
      by means of polymerase chain reaction and Southern blot analysis. In four T-cell
      clones of three of these patients, the bcr-abl transcript could be detected. None
      of 12 T-cell clones of the fourth patient disclosed detectable bcr-abl
      amplification product. Both CD4+ as well as CD8+ clones displayed fused bcr-abl
      sequences. These data imply that in CML some but not all T lymphocytes may
      originate from the Ph1-positive stem cell.

PMID- 1371077
TI  - Selection of benign primitive hematopoietic progenitors in chronic myelogenous
      leukemia on the basis of HLA-DR antigen expression.
AB  - Chronic myelogenous leukemia (CML) is a lethal malignancy of the human
      hematopoietic stem cell. Here we report that coexistent benign, primitive
      hematopoietic progenitors can be distinguished from their malignant counterparts
      in CML bone marrow by differences in cell surface antigen expression. Selection
      of bone marrow cells expressing the CD34 antigen but lacking the HLA-DR antigen
      results in recovery of small lymphocyte-like blasts, which initiate and sustain
      production of myeloid clonogenic progeny in vitro. Secondary clonogenic cells
      derived at week 1, 5, and 8 from long-term bone marrow cultures (LTBMCs)
      initiated with primitive progenitors, which lack HLA-DR antigens, exhibit neither
      the Philadelphia chromosome (Ph1) nor the corresponding bcr/abl mRNA
      characteristic of CML. In contrast, clonogenic cells recovered at week 1, 5, and
      8 from LTBMCs initiated with the CML HLA-DR+ population contain Ph1 and express
      bcr/abl mRNA. This observation indicates that it may be possible to select a
      population of viable, exclusively benign hematopoietic stem cells from CML bone
      marrow capable of repopulating the hematopoietic compartment following autologous
      bone marrow transplantation.

PMID- 1371079
TI  - Stem cell factor increases colony-forming unit-spleen number in vitro in synergy
      with interleukin-6, and in vivo in Sl/Sld mice as a single factor.
AB  - Hematopoiesis is thought to be modulated by interactions of progenitor cells with
      hematopoietic growth factors. We have shown that colony-forming units-spleen (CFU
      S) and repopulating stem cells require interleukin-3 (IL-3) to survive in vitro,
      and that CFU-S number and long-term repopulating ability can be increased by
      culture in the combination of IL-3 and IL-6. In this report, we describe the
      effects of stem cell factor (SCF) on CFU-S and repopulating stem cells. Injection
      of SCF into anemic Sl/Sld mice caused a twofold and 20-fold increase in CFU-S
      number in the bone marrow and spleen of treated animals, respectively. After 6
      days in suspension culture, CFU-S number increased threefold in cultures
      supplemented with SCF and IL-6, or SCF, IL-3, and IL-6 relative to the number at
      day 0. The long-term repopulating ability of cells cultured in SCF, IL-3, and IL
      6 was approximately sevenfold better than that of cells cultured in IL-3 or SCF.
      Similar experiments were performed on populations of bone marrow cells enriched
      for, or depleted of, CFU-S by elutriation and lineage subtraction. The
      combination of SCF and IL-6 increased CFU-S number approximately fourfold to
      eightfold in the CFU-S-enriched fraction, but had no effect on the CFU-S-depleted
      cells. These results show that SCF alone can increase CFU-S number in vivo, and
      in combination with other growth factors increases CFU-S numbers in vitro.

PMID- 1371080
TI  - The c-kit receptor ligand functions as a mast cell chemoattractant.
AB  - Mast cells accumulate at sites of neovascularization, solid tumors, and many
      immune reactions. Such accumulation requires directed migration of mature mast
      cells or their precursors. The nature of the chemoattractants that regulate mast
      cell motility and the identity of the receptors that mediate the chemotactic
      response are poorly understood. We have tested the ability of stem cell factor
      (SCF), a mast cell growth factor, to stimulate mast cell migration. Our results
      show that SCF is a potent mast cell attractant that stimulates directional
      motility of both mucosal and connective tissue-type mast cells. The activity is
      potentiated by costimulation with interleukin-3 (IL-3), another mast cell
      chemoattractant. SCF, a known ligand for the c-kit tyrosine kinase receptor, was
      unable to stimulate motility in W42 mutant mast cells, which have a defective c
      kit tyrosine kinase. However, W42 mast cells were still able to migrate in
      response to IL-3. These results show that SCF is a chemotactic factor as well as
      a growth factor and that the c-kit receptor can transduce signals leading to both
      cell proliferation and increased directional cell motility.

PMID- 1371081
TI  - Polyclonal hematopoiesis in interferon-induced cytogenetic remissions of chronic
      myelogenous leukemia.
AB  - Interferon (IFN) therapy of early chronic myelogenous leukemia (CML) frequently
      produces partial or complete cytogenetic remission of the disease. Patients with
      complete cytogenetic remission often continue on therapy for several years with
      bone marrow showing only diploid (normal) metaphases. We studied hematopoiesis in
      five female patients with major cytogenetic remissions from CML during IFN
      therapy. Clonality analysis using the BstXI PGK gene polymorphism showed that
      granulocytes were nonclonal in all patients during cytogenetic remission. BCR
      region studies showed rearrangement only in the one patient whose remission was
      incomplete at the time of sampling. Granulopoiesis is nonclonal in IFN-induced
      remissions of CML and may be derived from normal hematopoietic stem cells.

PMID- 1371082
TI  - Multiple myeloma.
AB  - Patients with multiple myeloma may present with insidious or acute clinical
      problems to wide variety of medical specialties. It is important for doctors to
      know how to diagnose myeloma accurately, to be aware of the clinical
      complications and to have some knowledge of the newer therapeutic approaches to
      chemotherapy and supportive treatment.

PMID- 1371083
TI  - Presenting a talk at an academic meeting.
AB  - Presenting a paper at an academic meeting or giving a lecture is a small but
      significant part of a doctor's work. Nearly all doctors initially dread such a
      prospect, but with practice and experience it need not be such an ordeal.

PMID- 1371084
TI  - Treatment of Paget's disease by weekly infusions of 3-aminohydroxypropylidene-1,1
      bisphosphonate (APD).
AB  - Thirty patients with symptomatic Paget's disease of bone were treated with weekly
      infusions of 30 mg APD for 6 weeks and followed for up to 3 years (mean 2 years).
      Bone pain diminished or disappeared in 83%. Six months following treatment the
      serum alkaline phosphatase (sAP) had normalized in 53% and had fallen by an
      average of 68% in the remainder. The average fall in sAP was 65% at 6 months, 59%
      at 1 year and 51% at 2 years. Urine hydroxyproline/creatinine ratios (OHp/Cr)
      fell by an average of 72% over the 6 weeks of treatment whilst serum bone gla
      protein (BGP) showed no significant change. However, there was a significant fall
      in the mean BGP of 25% by 6 months following treatment. Radionuclide bone scan
      abnormalities improved in all patients and showed complete resolution in two. The
      same regimen was used to retreat eight patients with a persistence or recurrence
      of symptoms after 1 year. At 6 months following retreatment the sAP had fallen to
      normal in four and in the remainder by an average of 39%. Two patients had a
      third course after a further year and by 6 months the sAP had fallen by an
      average of 50%. Normalization of sAP occurred in 86% of patients with a
      pretreatment sAP less than 900 iu/l (normal less than 300) and 89% of patients
      with a sAP less than 600 iu/l immediately following the course of treatment.
      Therefore, knowledge of the pretreatment and post-treatment sAP should enable
      prediction of the need for further therapy in most cases. We confirm that APD is
      an effective and well tolerated treatment for the management of Paget's disease,
      giving long-term suppression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371085
TI  - Determination of pre-orchiectomy serum levels of alpha-fetoprotein and human
      choriogonadotrophin in testicular cancer.

PMID- 1371086
TI  - Eosinophilic prostatitis and prostatic specific antigen.
AB  - Eosinophilic prostatitis is a rare form of abacterial prostatitis with uncertain
      aetiology. Its clinical presentation, like other types of abacterial prostatitis,
      commonly mimics carcinoma of the prostate. Transrectal ultrasound may be helpful
      in the diagnosis of prostatitis but histological confirmation is necessary.
      Prostatic specific antigen has been widely used in the diagnosis and follow-up of
      patients with prostatic carcinoma. High levels of this antigen (greater than 30
      micrograms/l) have been claimed to be highly specific for prostate cancer,
      although lesser elevations may also occur in patients with large benign prostate
      glands and in bacterial prostatitis. We report 3 patients with histologically
      proven eosinophilic prostatitis and high levels of prostatic specific antigen.
      This diagnosis may closely mimic carcinoma of the prostate and must be excluded
      by histological examination of biopsy material before treatment for presumed
      prostate carcinoma is initiated.

PMID- 1371087
TI  - Surgical palliation for pancreatic cancer: developments during the past two
      decades.
AB  - Improvements in pancreatic imaging over the past 20 years have revolutionized the
      preoperative diagnosis and assessment of resectability in patients with suspected
      pancreatic cancer. This review highlights the resultant trends in the surgical
      treatment of ductal carcinoma of the pancreas, comparing series reported between
      1981 and 1990 with those from the previous decade. Small but worthwhile gains
      have been achieved both in overall resection rate and in the survival rate from
      such resections. Nevertheless, 80 per cent or more of affected patients are still
      unsuitable for resection because of the extent of their disease. Laparotomy
      retains a crucial role in the management of carcinoma of the pancreatic head,
      although percutaneous and endoscopic stents provide a useful alternative for
      palliation of malignant obstructive jaundice in elderly patients or those with
      carcinomatosis. Operation provides the chance to confirm the nature and full
      extent of the tumour, to circumvent duodenal obstruction and to abolish pain,
      besides relieving jaundice without the need for tubes (with their potential to
      block). By contrast, operative treatment generally has much less to offer in
      patients with carcinoma of the pancreatic body, unless diagnosis and
      irresectability remain in doubt. In combination, radiotherapy and 5-fluorouracil
      may achieve more as adjuncts to palliative surgery than either agent alone. The
      increasing safety of pancreaticoduodenectomy raises the possibility of palliative
      resection in younger patients with limited but incurable disease.

PMID- 1371088
TI  - Tumor promoters induce basic fibroblast growth factor gene expression in human
      dermal fibroblasts.
AB  - Tumor-promoting phorbol esters have been shown previously to either induce or
      repress the expression of numerous cellular genes, and this property is likely to
      be important for the in vitro and in vivo biological effects of these compounds.
      In this report, we demonstrate that phorbol 12-myristate 13-acetate induces the
      accumulation of basic fibroblast growth factor mRNA and protein in human dermal
      fibroblasts. In contrast, acidic fibroblast growth factor expression was
      unaffected by this compound. The enhancement of basic fibroblast growth factor
      gene expression by phorbol 12-myristate 13-acetate was blocked by the
      isoquinolinesulfonamide derivative H7, a potent inhibitor of protein kinase C.
      Two additional tumor promoters that bind to and activate protein kinase C,
      phorbol 12,13-didecanoate and mezerein, also increased basic fibroblast growth
      factor mRNA levels. Basic fibroblast growth factor is a mitogen for many cell
      types and can stimulate angiogenesis; thus, some tumor promoter-induced cellular
      responses may be mediated by this polypeptide.

PMID- 1371089
TI  - Role of neovasculature and vascular permeability on the tumor retention of
      photodynamic agents.
AB  - A variety of photodynamic sensitizers (chloroaluminum sulfonated phthalocyanine,
      tetraphenyl porphine sulfonate, mono-L-aspartyl chlorin e6, Photofrin, chlorin
      e6, and Uroporphyrin dihydrochloride I) were characterized by their ability to be
      retained in EMT-6 tumors growing in BALB/c mice. Two properties uniquely
      associated with tumors, proliferating neovasculature and vascular permeability,
      were tested for their relative importance in retaining the photosensitizer. A
      chick embryo model was used to compare photosensitizer uptake/retention in
      proliferating and nonproliferating neovasculature with retention in proliferating
      nonvascular tissue. Our results provide evidence that photosensitizers which are
      preferentially retained by tumors have a selective affinity for proliferating
      neovasculature. The chloroaluminum sulfonated phthalocyanine and tetraphenyl
      porphine sulfonate compounds possess the greatest affinity for proliferating
      neovasculature relative to nonvascular tissue, while the phthalocyanine has the
      largest tumor/normal differential in vivo of all the photosensitizers tested.
      Chlorin e6 and uroporphyrin dihydrochloride I were the only photosensitizers
      which were not retained in greater amounts by tumor tissues relative to normal
      tissues. Using a delayed-type hypersensitivity reaction, extended and constant
      vascular permeability was induced in BALB/c mice. Vascular permeability was
      quantitated by Evans blue extraction from the delayed-type hypersensitivity
      sites. Interestingly, leaky vessels alone did not result in photosensitizer
      retention, as seen with tumors. These data demonstrate that tumor-retained
      photosensitizers possess a selective affinity for proliferating neovasculature
      and that vascular permeability alone is not sufficient to retain these
      sensitizers.

PMID- 1371090
TI  - The combination of gamma-interferon and tumor necrosis factor causes a rapid and
      extensive differentiation of human neuroblastoma cells.
AB  - Neuroblastoma (NB), a tumor originating from the sympathetic nervous system, is
      the most common extracranial neurological tumor of childhood. Human NB cells may
      differentiate in vitro under treatment with biological agents, as gamma
      interferon (IFN-gamma) and tumor necrosis factor (TNF). Unfortunately, NB cell
      lines resistant to the differentiation-inducing effects of both drugs have been
      observed. Here we demonstrate that a combination of IFN-gamma plus TNF causes
      extensive and generalized differentiation of NB cells toward a neuronal
      phenotype. Both IFN-gamma and TNF, given alone, moderately reduced cell growth
      and induced partial morphological maturation. Their combination further reduced
      cell proliferation. The combined treatment gave a synergistic rather than
      additive cytostatic effect, documented also by a dramatically enhanced
      differentiation toward a neuronal morphology. Membrane immunofluorescence showed
      a homologous and heterologous up-regulation of IFN-gamma receptor, as well as a
      marked induction of HLA Class I antigens and, to a lesser extent, of Class II
      antigens on NB cells induced to differentiate. Treatment of NB cell lines with
      IFN-gamma/TNF results in the induction of a differentiated phenotype, as
      indicated by the increased expression of the Mr 160,000 and 200,000 neurofilament
      proteins and that of microtubule-associated proteins. Evaluation of biochemical
      markers of neuronal differentiation confirmed the ability of the combined
      treatment to induce neuroblast maturation. These results suggest that the
      combination of IFN-gamma and TNF should be considered for experimental clinical
      trials in neuroblastoma.

PMID- 1371091
TI  - Introduction of the ras oncogene transforms a simian virus 40-immortalized
      hepatocyte cell line without loss of expression of albumin and other liver
      specific genes.
AB  - Activated c-Ha-ras DNA sequences were introduced by transfection into a low
      passage simian virus 40 (SV40)-immortalized rat hepatocyte cell line, CWSV1, and
      stable ras transfectant cell lines were established to determine the effect of
      the addition of the activated c-Ha-ras oncogene on growth properties and
      differentiation. Control transfectant cell lines were generated by transfection
      with neo alone. CWSV1 cells at low passage and the control transfectants were not
      tumorigenic. The ras transfectants demonstrated anchorage-independent growth and
      were highly tumorigenic in syngeneic hosts. CWSV1 cells produce liver-like levels
      of albumin and express other liver-specific genes. The ras transfectants
      expressed RNA for albumin, transferrin, and the transcription factor HNF-1 at
      similar levels to the parental CWSV1 cells, indicating that the alterations in
      growth properties and tumorigenic potential of these cells did not decrease the
      ability of the cells to express several genes that are associated with hepatocyte
      differentiation. The addition of the ras oncogene did not induce the expression
      of alpha-fetoprotein and had no specific effect on expression of glutathione S
      transferase-P. The tumors produced by the ras transfectants were not well
      differentiated; however, the cells in the tumors and tumor cell lines derived
      from the tumors continued to produce albumin and did not produce alpha
      fetoprotein. We conclude that the addition of the activated c-Ha-ras oncogene to
      immortalized CWSV1 cells transformed these cells as measured by morphology,
      growth properties, and tumorigenicity without reducing their ability to express
      albumin and other significant liver-specific genes.

PMID- 1371092
TI  - Successful treatment of human acute T-cell leukemia in SCID mice using the anti
      CD7-deglycosylated ricin A-chain immunotoxin DA7.
AB  - The study of new therapeutic approaches for refractory human leukemia has been
      hampered by the lack of relevant in vivo models with disseminated disease,
      particularly T acute lymphoblastic leukemia (T-ALL). In the present study we
      evaluated methods for establishing and therapy of a human T-ALL cell line (MT
      ALL) in 73 SCID mice. MT-ALL is a T-cell receptor alpha/beta +, CD3+, and CD7+
      leukemia cell line, derived from a patient with refractory disease and early
      death. Injection of 5 x 10(7) MT-ALL cells i.v. caused disseminated human
      leukemia in hematopoietic and nonhematopoietic organs in 100% of SCID mice (n =
      9) leading to death or terminal disease at 65 to 70 days after a uniform clinical
      course. To study possible therapeutic approaches for disseminated leukemia we
      utilized an immunotoxin, DA7, constructed by chemically linking the mouse IgG2b
      anti-CD7(3A1E) monoclonal antibody which recognizes a pan-T-cell marker expressed
      on almost all T-cell leukemias to deglycosylated ricin A-chain, a catalytic plant
      toxin and inhibitor of protein synthesis. Administration of DA7 led to greater
      than 5 log kill of clonogenic MT-ALL cells in vitro and selectively inhibited
      protein synthesis. DA7 was administered to mice at a dose of 10
      micrograms/mouse/day for 5 consecutive days starting 8 days after i.v.
      inoculation of leukemia. The immunotoxin therapy resulted in significant long
      term survival over 348 days compared to untreated or control mice treated with
      anti-CD7 antibody and deglycosylated ricin A-chain which were all dead by day 70
      (P less than 0.001). Even after more than 11 months there was no evidence of
      disease in 82% of the DA7 treated animals. SCID mice given i.p. injections (n =
      9) developed an i.p. tumor mass but demonstrated metastasis outside the
      peritoneum with disseminated leukemia in hematopoietic and nonhematopoietic
      organs, a finding different from most conventional nude mouse models. The
      leukemia was fatal in 100% and killed the animals at 68-95 days. SCID mice given
      i.p. injections of MT-ALL completely responded to therapy with DA7, resulting in
      survival of 100% of the animals (n = 10) at 216 days (P less than 0.001 compared
      to untreated animals). Anti-CD7 antibody, deglycosylated ricin A-chain, and a
      control anti-melanoma immunotoxin (IND1-RTA) showed no therapeutic effect. We
      conclude that DA7 is an effective in vivo therapeutic agent against human MT-ALL
      in the SCID mouse system, suggesting potential usefulness for therapy of humans
      with poor prognosis T-cell leukemia.

PMID- 1371093
TI  - Is hypomagnesemia arrhythmogenic?
AB  - An understanding of the role of magnesium in cardiac conduction is complicated by
      the multiplicity of intracellular events coordinated by the magnesium ion.
      Several reports have cited magnesium deficiency as the cause of a variety of
      ventricular and supraventricular arrhythmias. On further inspection, the
      circumstances of each report strongly suggest the coexistence of significant
      potassium depletion; isolated hypomagnesemia as a cause of arrhythmia is not
      reported. This discussion brings together new data from basic science with that
      of clinical research to refute the suggestion that isolated hypomagnesemia is
      arrhythmogenic. However, there is sufficient evidence to indicate that
      hypomagnesemia will significantly exacerbate the proarrhythmic effect of
      hypokalemia, particularly if occurring in the presence of digoxin toxicity.
      Potassium and magnesium depletion are commonly concomitant, and simultaneous
      repletion of both ions in the presence of hypokalemia-induced arrhythmia would be
      both logical and effective. The beneficial effects of intravenous magnesium in
      the acute control of ventricular tachyarrhythmia are concluded to occur as a
      result of a separate antiarrhythmic action, quite independent of underlying
      magnesium balance.

PMID- 1371094
TI  - Chemotherapy-induced myocardial infarction in a young man with Hodgkin's disease.
AB  - A 32-year-old male with stage IIIA nodular sclerosing Hodgkin's disease and no
      cardiac risk factors presented with chest pain after receiving chemotherapy
      consisting of multiple drugs, including vinca alkaloids. He completed an
      uncomplicated anterior wall myocardial infarction. Coronary angiography
      documented the absence of significant coronary artery disease. Exercise stress
      testing with gated scan confirmed loss of anterior wall motion and a decreased
      left ventricular ejection fraction. Vascular toxicity, including, rarely,
      myocardial infarction, has been reported following antineoplastic regimens
      containing vinca alkaloids. Hypercoagulable states, cardiac invasion by tumor,
      and coronary artery spasm are possible etiologies. Of these, coronary artery
      spasm appears most likely. Management should include discontinuation of the
      offending drug and supportive care.

PMID- 1371095
TI  - Radiology in malabsorption.

PMID- 1371096
TI  - Hypertonic saline and dextran for intraoperative fluid therapy: more for less.

PMID- 1371097
TI  - Patterns of cytokines, plasma endotoxin, plasminogen activator inhibitor, and
      acute-phase proteins during the treatment of severe sepsis in humans.
AB  - OBJECTIVE: To study the patterns of plasma concentrations of endotoxin, tumor
      necrosis factor-alpha (TNF), interleukin-6 (IL-6), plasminogen activator
      inhibitor-1, C-reactive protein, and serum amyloid A during the treatment of
      human sepsis. DESIGN: A prospective case series study. SETTING: ICU of the
      Department of Internal Medicine, University Hospital Groningen, The Netherlands.
      PATIENTS: Twenty consecutive patients (11 female, 9 male, mean age 67 yrs) with
      clinically defined sepsis. Eighteen patients were admitted from the outpatient
      emergency ward; two patients were already inpatients. The control group (n = 7)
      comprised patients with nonseptic shock. MEASUREMENTS AND MAIN RESULTS: Ten (50%)
      septic patients had detectable endotoxemia (greater than 5 (ng/L). TNF
      concentrations on admission were increased in 94% of the septic patients, whereas
      IL-6 and plasminogen activator inhibitor plasma concentrations were increased in
      all septic patients. The septic group showed significantly (p less than .05)
      higher concentrations of TNF, IL-6, plasminogen activator inhibitor-1, C-reactive
      protein, and serum amyloid A compared with the nonseptic patients. In the septic
      group, we found a correlation of both IL-6 and plasminogen activator inhibitor
      concentrations with severity of illness (r2 = .33, p less than .05; r2 = .22, p
      less than .05, respectively). After the start of antibiotic treatment, high
      concentrations of TNF and plasminogen activator inhibitor persisted in the
      nonsurvivors in contrast to decreasing concentrations in most of the survivors.
      After an initial increase in seven patients, IL-6 concentrations decreased in all
      septic patients and also in nonsurvivors. CONCLUSIONS: This study confirms
      previous findings that: a) TNF is a major mediator involved in the pathogenesis
      of septic shock; b) plasminogen activator inhibitor activity is significantly
      increased in septic patients and might be involved in the pathogenesis of
      disseminated intravascular coagulation associated with sepsis; and c) IL-6 is
      involved in the pathophysiology of septic shock, although further studies are
      needed to determine whether IL-6 is directly involved in mediating the lethal
      complications of septic shock or whether it should be considered an "alarm
      hormone" that reflects endothelial cell injury. Our findings also suggest that
      the concentrations and trends of these mediators during treatment are valuable
      for monitoring septic patients.

PMID- 1371098
TI  - Resuscitation of intraoperative hypovolemia: a comparison of normal saline and
      hyperosmotic/hyperoncotic solutions in swine.
AB  - BACKGROUND AND METHODS: We compared a hypertonic saline-dextran solution (7.5%
      NaCl/6% dextran-70) with 0.9% NaCl (normal saline) for treatment of
      intraoperative hypovolemia. Fourteen anesthetized pigs (mean weight 36.3 +/- 2.1
      kg) underwent thoracotomy, followed by hemorrhage for 1 hr to reduce mean
      arterial pressure to 45 mm Hg. A continuous infusion of either solution was then
      initiated and the flow rate was adjusted to restore and maintain aortic blood
      flow at baseline levels for 2 hrs. RESULTS: Full resuscitation to initial values
      of aortic blood flow was achieved with both regimens, but the normal saline group
      required substantially larger volumes and sodium loads to maintain stable
      hemodynamic values. Normal saline resuscitation produced increases in right
      ventricular preload (central venous pressure) and afterload (pulmonary arterial
      pressure and pulmonary vascular resistance), resulting in increased right
      ventricular work. CONCLUSIONS: Hypertonic saline-dextran solution resuscitation
      of intraoperative hypovolemia is performed effectively with smaller fluid and
      sodium loads, and is devoid of the deleterious effects associated with fluid
      accumulation induced by a conventional isotonic solution regimen.

PMID- 1371099
TI  - Effect of hydroxyethyl starch solutions on blood glucose concentrations in
      diabetic and nondiabetic rats.
AB  - BACKGROUND AND METHODS: The effects of iv infusions of 6% hetastarch or 10%
      pentastarch on blood glucose concentrations were tested in 12 nondiabetic and 12
      streptozotocin-induced diabetic pentobarbital-anesthetized Sprague-Dawley rats
      weighing 313 to 473 g. All rats were paralyzed and mechanically ventilated. After
      control measurements of blood glucose concentrations were taken, rats were
      divided into four groups. Groups 1 (n = 6) and 2 (n = 6) comprised nondiabetic
      rats that received iv infusions of hetastarch or pentastarch, respectively, at a
      rate of 2.0 mL over 30 mins. Groups 3 (n = 6) and 4 (n = 6) comprised diabetic
      rats that also received iv hetastarch or pentastarch, respectively, at the same
      rate and duration of infusion. RESULTS: Neither hetastarch nor pentastarch
      infusions significantly altered blood glucose values over the 3-hr study period,
      regardless of whether the rats were diabetic or nondiabetic. CONCLUSIONS:
      Assuming these data are transferable to humans, the authors conclude that
      hydroxyethyl starch solutions do not produce or exacerbate hyperglycemia, and
      furthermore, that their use is not contraindicated in subjects having
      hyperglycemia from diabetes mellitus or iatrogenic causes.

PMID- 1371100
TI  - [The palliative therapy of malignant esophageal obstruction with self-expanding
      metal endoprostheses].
AB  - A total of 23 self-expanding metal stents were implanted in 17 patients (12 men,
      5 women; mean age 66 [44-83] years) with inoperable malignant obstruction of the
      oesophagus or the oesophago-gastric junction. A primary success was achieved in
      all, a good functional result in 16 (94%). There were no complications. In the
      follow-up period (mean of 15.2 +/- 13 weeks) re-obstruction by the tumour process
      occurred in three patients. Twelve patients died after a mean survival time of
      15.8 +/- 14 weeks. In ten of these the stent was still patent at death, while two
      had again developed dysphagia. The cumulative patency rate of the stents was 79%.
      These observations indicate that self-expanding metal stents can achieve
      satisfactory palliation in dysphagia due to a malignancy. The mortality and
      morbidity rates of the method seem to be less than those of other palliative
      measures.

PMID- 1371101
TI  - Flow-induced release of adenosine 5'-triphosphate from endothelial cells of the
      rat mesenteric arterial bed.
AB  - Adenosine 5'-triphosphate (ATP) was released into the perfusate of rat isolated
      mesenteric arterial beds during each of two consecutive increases in flow. There
      was no significant difference between the amounts of ATP released on each
      occasion. Substance P was also released into the perfusate by increased flow,
      although its release was more variable. Removal of the endothelium of the
      mesenteric vessels with sodium deoxycholate led to a significant reduction (74%)
      in the amount of ATP released compared with the release before the endothelium
      had been removed. This suggests that the ATP released into the mesenteric
      arterial perfusate during increased flow arises from endothelial cells.

PMID- 1371102
TI  - An improved thioflavine S method for staining neurofibrillary tangles and senile
      plaques in Alzheimer's disease.
AB  - Large differences are usually observed when standard staining methods for a
      number of pathological lesions in neurodegenerative disorders are compared. With
      the modified thioflavine S method presented here (easy and cheap to perform), the
      morphological appearance of the stained neurofibrillary tangles (NFT) and senile
      plaques (SP) is greatly improved. Furthermore, the intense contrast between
      stained lesions and background obtained with this technique permits an accurate
      automatic quantification of NFT and SP using a computer-assisted image analysis
      system.

PMID- 1371103
TI  - Correlation between first disease-free interval from mastectomy to second disease
      free interval from chest wall resection.
AB  - Between 24 November 1977 and 16 September 1988, 18 consecutive chest wall
      resections for recurrent breast cancer after failure of radiotherapy, were
      evaluated as of 1 January 1990. Chest wall involvement was the only site of
      recurrence in 14 patients (Group I), and the most painful of the multiple
      recurrences in the remaining four (Group II). Of Group I, chest wall recurrence
      was local in eight patients (four with necrosis after radiotherapy), regional in
      four, and distant in two. Chest wall reconstruction was effected by contralateral
      breast flap in six, by random cutaneous flap in seven and by myocutaneous flap in
      the remaining five. Cosmetic results were better if both marlex mesh and
      myocutaneous flap were used. Of Group I, at surgical/pathological staging, one
      recurrence with sarcomatous findings, two multiple recurrences and residual
      cancer in all necrosed local recurrences were found: in three of these cases
      radionecrosis was prominent. Mortality was 0% and surgical morbidity 5%. For
      Group I, median disease-free interval from mastectomy was extended from 1611 days
      to 3220 by recurrence resection, and disease-free interval from chest wall
      resection was 28% cancer-free at 1657 days, without any difference between the
      local vs regional-distant recurrence. Correlation factor between first and second
      disease interval was 0.99 and R2 was 0.98. For Group II, survival was 0% at 635
      days. Chest wall resection must be considered as an important part of palliative
      treatment in breast cancer, but the results reflects the biology of the disease
      more than the chest wall surgery.

PMID- 1371104
TI  - Adenomatoid tumours: a mucin histochemical and immunohistochemical study.
AB  - We have examined 16 cases of adenomatoid tumour using a panel of monoclonal and
      polyclonal antibodies and also stained them for the presence of hyaluronidase
      sensitive alcianophilic material. Fourteen cases expressed cytokeratins and a
      proportion of these also expressed S-100 protein, neuron-specific enolase,
      vimentin, and human milk fat globule protein 2. The same 14 cases also showed
      hyaluronidase-sensitive staining with alcian blue. No expression of factor VIII
      related antigen was seen in these cases. We conclude that this provides further
      evidence of a mesothelial origin of these tumours. The remaining two cases did
      not express cytokeratins and no hyaluronidase-sensitive staining with alcian blue
      was seen. They did however express factor VIII-related antigen. Although they
      were morphologically indistinguishable from the other 14 cases, we suggest that
      they should be more properly regarded as angiomas.

PMID- 1371105
TI  - Specificity and protective activity of murine monoclonal antibodies directed
      against the capsular polysaccharide of type III group B streptococci.
AB  - We have obtained 41 monoclonal antibodies directed against type III group B
      streptococci by immunizing Balb/c mice with formalin-killed bacteria. All of
      these antibodies reacted with purified type-specific carbohydrate by enzyme
      linked immunosorbent assay and immunoprecipitation tests. The epitope recognized
      by all of these antibodies was associated with terminal sialic acid residues, as
      indicated by abrogation of immune reactions by treatment of the type-specific
      carbohydrate with neuraminidase. Two purified monoclonal antibodies (the IgM P9D8
      and the IgG3 P4F12) were further characterized for their protective activity in a
      neonatal rat model of infection. P9D8 and P4F12 antibodies were significantly
      protective when administered in a dose of 0.5 and 2.5 mg/kg, respectively, at the
      same time as 3 x 10(5) colony forming units of type III streptococci. Protection
      was still observed when the antibodies were given up to 9 h after challenge. No
      protection was afforded against infections with type Ia/c and II streptococci.
      Similarly, both antibodies effectively opsonized type III, but not Ia, Ib or II
      bacteria, in an in vitro assay. These and similar, previously described,
      monoclonal antibodies may be useful, possibly after "humanization" by genetic
      engineering, for the therapy of neonatal group B streptococcal infections.

PMID- 1371106
TI  - Immunohistochemical study on the pattern of 50 kd cytokeratin in psoriasis.
AB  - Three biopsies of normal skin and 15 biopsies collected from patients with
      psoriasis vulgaris were analyzed for the expression of the 50 kd cytokeratin
      using direct immunofluorescence and ABC technique before and after local
      treatment with anthralin 0.1% in a petrolatum base, with 0.05% betamethasone
      dipropionate cream, and finally, after PUVA treatment. Antiserum against the 50
      kd anti-cytokeratin reacted with tissue sections of normal skin, staining cells
      in the basal layer, while the psoriatic skin sections before the various
      treatments showed a staining concerning the whole thickness of the epidermis.
      After the various therapies, the 50 kd cytokeratin immunoreactivity was observed
      only in the basal layer of those psoriatic skin sections that showed complete
      clinical clearing, while it was observed in the whole thickness of psoriatic
      patches that did not clear. These data suggest that the normalization of the 50
      kd cytokeratin expression pattern can be considered as a marker of clinical
      remission of psoriasis.

PMID- 1371107
TI  - The Hsp56 component of steroid receptor complexes binds to immobilized FK506 and
      shows homology to FKBP-12 and FKBP-13.
AB  - Extracts from human Jurkat cells or from calf thymus contain a 60-kDa protein
      that is bound to immobilized FK506. As expected, the NH2-terminal sequences of
      the 60-kDa protein from these two species were found to be nearly the same. We
      were surprised to discover, however, that the sequence of the human protein was
      identical to that of Hsp56, a heat shock protein of unknown function that has
      been shown to be a component of several steroid receptor complexes. Further
      analysis of the calf thymus protein revealed a peptide with homology to a region
      near the COOH terminus of both FKBP-12 and FKBP-13. It would appear, therefore,
      that this 60-kDa protein, or as we refer to it provisionally, "Hsp56," could have
      the capacity to bind FK506 directly. These observations lead us to speculate that
      "Hsp56" may mediate immunosuppression and inhibition of T-cell proliferation by
      FK506 and may do so via a cytosolic signal transduction pathway separate, but not
      necessarily exclusive, from that of FKBP-12 and FKBP-13.

PMID- 1371108
TI  - Lithium inhibits hepatic gluconeogenesis and phosphoenolpyruvate carboxykinase
      gene expression.
AB  - Incubation of isolated hepatocytes from fasted rats with 20 mM LiCl for 1 h
      decreased glucose production from lactate, pyruvate, and alanine. In addition,
      phosphoenolpyruvate carboxykinase (PEPCK) gene expression in FTO-2B rat hepatoma
      cells was inhibited by treatment with LiCl. Lithium was also able to counteract
      the increased PEPCK mRNA levels caused by both Bt2cAMP and dexamethasone, in a
      concentration-dependent manner. A chimeric gene containing the PEPCK promoter (
      550 to +73) linked to the amino-3-glycosyl phosphotransferase (neo) structural
      gene was transduced into FTO-2B cells using a Moloney murine leukemia virus-based
      retrovirus. In these infected cells, 20 mM LiCl decreased both the concentration
      of neo mRNA transcribed from the PEPCK-neo chimeric gene and mRNA from the
      endogenous PEPCK gene. Lithium also inhibited the stimulatory effect of Bt2cAMP
      and dexamethasone on both genes. The stability of neo mRNA was not altered by
      lithium, since in cells infected with retrovirus containing only the neo gene
      transcribed via the retroviral 5'-LTR and treated with 20 mM LiCl, no change in
      neo mRNA levels was observed. The intraperitoneal administration of LiCl to rats
      caused a decrease in hepatic PEPCK mRNA, indicating that lithium could also
      modify gene expression in vivo. The effects of lithium were not due to an
      increase in the concentration of insulin in the blood but were correlated with an
      increase in hepatic glycogen and fructose 2,6-bisphosphate levels. These results
      indicate that lithium ions, at concentrations normally used therapeutically for
      depression in humans, can inhibit glucose synthesis in the liver by a mechanism
      which can selectively modify the expression of hepatic phosphoenolpyruvate
      carboxykinase.

PMID- 1371109
TI  - Modulation of the mitochondrial megachannel by divalent cations and protons.
AB  - In patch-clamp experiments on rat liver mitoplasts, the 1.3 nanosiemens (in 150
      mM KCl) mitochondrial megachannel was activated by Ca2+ and competitively
      inhibited by Mg2+, Mn2+, Ba2+, and Sr2+. Cyclosporin A, which inhibits the
      megachannel, also showed a competitive behavior versus Ca2+. The pore is
      regulated by pH in the physiological range; lower pH values cause its closure in
      a Ca(2+)-reversible manner. The modulating sites involved in these effects are
      located on the matrix side of the membrane. As illustrated in the companion paper
      (Bernardi, P., Vassanelli, S., Veronese, P., Colonna, R., Szabo, I., and Zoratti,
      M. (1992) J. Biol. Chem. 267, 2934-2939), the calcium-induced permeability
      transition of mitochondria is affected by these various agents in a similar
      manner. The results support the identification of the megachannel with the pore
      believed to be involved in the permeabilization process. The kinetic
      characteristics of the single channel events support the idea that the
      megachannel is composed of cooperating subunits.

PMID- 1371110
TI  - Isolation and characterization of a cDNA clone encoding a cognate 70-kDa heat
      shock protein of the chloroplast envelope.
AB  - The translocation of proteins into the endoplasmic reticulum, the mitochondrion,
      and the chloroplast has recently been shown to involve homologues of the highly
      conserved 70-kDa heat shock protein (HSP70) family. In this study, we have
      isolated and sequenced a full-length cDNA clone encoding a cognate 70-kDa heat
      shock protein of the spinach chloroplast envelope (SCE70). The cDNA insert is
      2,535 base pairs long and codes for 653 amino acid residues of a protein with a
      predicted molecular mass of 71,731 daltons. The deduced amino acid sequence shows
      a high degree of homology with HSP70 proteins from other organisms. Southern
      genomic and RNA analyses reveal different hybridization patterns than that
      observed for a heat-inducible 70-kDa protein gene. The protein synthesized from
      the SCE70 cDNA insert co-migrates with a 70-kDa polypeptide of the chloroplast
      envelope following sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
      Western blot analysis and import studies indicate that SCE70 is associated with
      the chloroplast outer envelope. The import data suggest that SCE70 is targeted to
      the envelope membrane via a pathway different from other plastidic precursors but
      similar to that recently reported for outer envelope proteins SOE1 and OM14.

PMID- 1371111
TI  - Anion uniport in plant mitochondria is mediated by a Mg(2+)-insensitive inner
      membrane anion channel.
AB  - It has long been established that the inner membrane of plant mitochondria is
      permeable to Cl-. Evidence has also accumulated which suggests that a number of
      other anions such as Pi and dicarboxylates can also be transported
      electrophoretically. In this paper, we present evidence that anion uniport in
      plant mitochondria is mediated via a pH-regulated channel related to the so
      called inner membrane anion channel (IMAC) of animal mitochondria. Like IMAC, the
      channel in potato mitochondria transports a wide variety of anions including NO3
      , Cl-, ferrocyanide, 1,2,3-benzene-tricarboxylate, malonate, Pi, alpha
      ketoglutarate, malate, adipate, and glucuronate. In the presence of nigericin,
      anion uniport is sensitive to the medium pH (pIC50 = 7.60, Hill coefficient = 2).
      In the absence of nigericin, transport rates are much lower and much less
      sensitive to pH, suggesting that matrix H+ inhibit anion uniport. This conclusion
      is supported by measurements of H+ flux which reveal that "activation" of anion
      transport at high pH by nigericin and at low pH by respiration is associated with
      an efflux of matrix H+. Other inhibitors of IMAC which are found to block anion
      uniport in potato mitochondria include propranolol (IC50 = 14 microM, Hill
      coefficient = 1.28), tributyltin (IC50 = 4 nmol/mg, Hill coefficient = 2.0), and
      the nucleotide analogs Erythrosin B and Cibacron Blue 3GA. The channel in plant
      mitochondria differs from IMAC in that it is not inhibited by matrix Mg2+,
      mercurials, or N,N'-dicyclohexylcarbodiimide. The lack of inhibition by Mg2+
      suggests that the physiological regulation of the plant channel may differ from
      IMAC and that the plant IMAC may have functions such as a role in the
      malate/oxaloacetate shuttle in addition to its proposed role in volume
      homeostasis.

PMID- 1371112
TI  - Ion channels are likely to be involved in the two steps of phage T5 DNA
      penetration into Escherichia coli cells.
AB  - Phage T5 injects its DNA into Escherichia coli cells in two steps; 8% of the
      chromosome is first injected, and then there is a pause during which proteins
      encoded by this DNA fragment are synthesized allowing the remaining DNA to be
      injected. Using a potassium-selective electrode, we show that the injection of
      the two DNA fragments is associated with an efflux in two steps, of cytoplasmic
      potassium. The rate of efflux is linearly related to the number of added phages
      suggesting that each phage induces the formation of at least one channel in the
      inner membrane. The first efflux occurs even in depolarized cells suggesting that
      the insertion and the opening of the channel can take place in the absence of the
      electrochemical gradient of protons (delta mu H+). The channel is in a closed
      configuration during the time required for the synthesis of the phage-encoded
      proteins; this closing and the second efflux are prevented by the depolarization
      of the cell. The insertion of the channel in the inner membrane requires a fluid
      membrane. The results obtained suggest that the function of this channel is to
      translocate phage T5 DNA.

PMID- 1371113
TI  - Identification of the transcriptionally active genes of the chorionic
      gonadotropin beta gene cluster in vivo.
AB  - The chorionic gonadotropin beta (CG beta) subunit is encoded by a multigene
      cluster composed of six homologous sequences (genes or pseudogenes). They are
      primarily distinguished by sequences in the 5' nontranslated region of the first
      exon. To determine which CG beta genes are active in vivo, we employed the
      reverse transcription-polymerase chain reaction technique. DNA complementary to
      RNA from placenta tissue and a choriocarcinoma cell line was subjected to
      polymerase chain reaction with CG beta-specific primers. The amplified DNA was
      cloned into M13 and sequenced. Most of steady-state CG beta mRNAs are transcribed
      from CG beta genes, 5, 3, and 8. The level of expression is beta 5 greater than
      beta 3 = beta 8 greater than beta 7, beta 1/2. Transcripts from the CG beta 1 and
      CG beta 2 genes, which were previously considered pseudogenes because of their
      noncanonical splice site, were detected. These CG beta transcripts arising from
      alternative splicing sites in the CG beta 1/2 genes were also detected in
      polysomes which suggests they are translation-competent. Northern blotting with a
      CG beta 1/2 probe revealed low amounts of CG beta 1/2 transcripts which were
      smaller than the transcripts of the other genes. The results indicate that at
      least five, and possibly all six, CG beta genes are transcribed in vivo, and at
      least one of them (CG beta 1 and/or CG beta 2) undergoes alternative splicing.

PMID- 1371114
TI  - Human lymphocytes transcribe the cystic fibrosis transmembrane conductance
      regulator gene and exhibit CF-defective cAMP-regulated chloride current.
AB  - Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasians,
      primarily affecting epithelial tissues of the lung and gut. Mutations in a single
      gene, the cystic fibrosis transmembrane conductance regulator (CFTR), are
      responsible for this disease. Whether a physiological defect exists in the immune
      system of CF patients has remained controversial. A chloride ion transport defect
      has been described in human CF-derived lymphocytes; however, it has not been
      possible to detect CFTR mRNA in lymphocytes. We report here that normal human B
      lymphoblasts display whole cell Cl- conductances induced by calcium-mediated
      pathways, volume regulation, and cAMP which are equivalent to currents described
      in epithelial cells. B-lymphoblasts from CF-affected humans demonstrated
      defective Cl- conductance regulation by cAMP but preserved regulation by calcium
      mediated and volume regulation mechanisms. CFTR involvement in cAMP regulation of
      Cl- conductance in lymphocytes is further supported by our demonstration of the
      presence of appropriately spliced CFTR mRNA segments in human B and T lymphocytes
      as detected by an optimized reverse-transcription and polymerase chain reaction
      approach. The identity of the amplified products was confirmed by hybridization
      to CFTR-specific probes and DNA sequencing. Furthermore, the 3'-end of the gene
      was found in a T cell cDNA library. We conclude that CFTR mRNA is expressed in
      lymphocytes, consistent with the cAMP regulation of chloride transport present in
      normal lymphocytes but defective in CF-derived lymphocytes.

PMID- 1371116
TI  - Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a
      mutation in the initiation codon of their common gene.
AB  - Sphingolipid activator proteins (SAPs) are small, nonenzymic glycoproteins that
      stimulate lysosomal degradation of various sphingolipids. SAP-1, SAP-2, and two
      additional potential activator proteins are derived from a common precursor by
      proteolytic processing. A severe case of sphingolipid storage disease that led to
      death within 16 weeks was attributed to a possible total deficiency of the SAPs
      generated by this gene (Harzer, K., Paton, B. C., Poulos, A., Kustermann-Kuhn,
      B., Roggendorf, W., Grisar, T., and Popp, M. (1989) Eur. J. Pediatr. 149, 31-39).
      Analysis of the SAP precursor cDNA from the patient and his fetal sibling showed
      an A to T transversion in the initiation codon. Allele-specific oligonucleotide
      hybridization revealed that both parents are heterozygous carriers for this
      mutation. In pulse-chase experiments using antisera raised against SAP-1 or SAP
      2, no cross-reacting material could be detected in the patients' fibroblasts.

PMID- 1371115
TI  - Characterization of mouse thrombospondin 2 sequence and expression during cell
      growth and development.
AB  - Thrombospondin (TSP) is an extracellular matrix glycoprotein whose expression has
      been associated with a variety of cellular processes including growth and
      embryogenesis. The recent discovery of the existence of a second mouse TSP gene
      necessitates careful examination of the discrete biochemical and functional
      properties associated with each molecule. In this report, the primary structures
      of human TSP, mouse TSP1 (mTSP1), mouse TSP2 (mTSP2), and chicken TSP are
      compared; and the expression of mTSP1 and mTSP2 during embryogenesis and growth
      factor-mediated cell proliferation is examined. The cloning and sequencing of the
      entire coding regions of mTSP1 and mTSP2 revealed considerable conservation of
      residues critical for TSP structure and function; these data suggest that TSP2 is
      capable of trimer formation and many of the same cell-surface and ligand
      interactions that mediate TSP function. Comparison of the various TSP sequences
      also allowed the assignment based on sequence homology of previously reported
      human TSP as TSP1 and chicken TSP as TSP2. mTSP2, like mTSP1, was shown to be a
      primary response gene when quiescent Swiss 3T3 cells were stimulated with serum,
      platelet-derived growth factor BB, basic fibroblast growth factor, or interleukin
      1 beta. Interestingly, TSP1 and TSP2 exhibited markedly different tissue- and
      stage-specific patterns of mRNA expression during mouse embryogenesis, implying
      that the two TSP molecules possess discrete functional properties important for
      development. Additionally, the TSP genes (Thbs1 and Thbs2) were mapped to single
      loci on mouse chromosomes 2 and 17, respectively.

PMID- 1371117
TI  - PPIase catalysis by human FK506-binding protein proceeds through a conformational
      twist mechanism.
AB  - FK506-binding protein (FKBP) catalyzes the cis-trans isomerization of the
      peptidyl-prolyl amide bond (the PPIase reaction) and is the major intracellular
      receptor for the immunosuppressive drugs FK506 and rapamycin. One mechanism
      proposed for catalysis of the PPIase reaction requires attack of an enzyme
      nucleophile on the carbonyl carbon of the isomerized peptide bond. An alternative
      mechanism requires conformational distortion of the peptide bond with or without
      assistance by an enzyme hydrogen bond donor. We have determined the kinetic
      parameters of the human FKBP-catalyzed PPIase reaction. At 5 degrees C, the
      isomerization of Suc-Ala-Leu-Pro-Phe-pNA proceeds in 2.5% trifluorethanol with
      kcat = 600 s-1, Km = 0.5 mM and kcat/Km = 1.2 x 10(6) M-1s-1. The kcat/Km shows
      little pH dependence between 5 and 10. A normal secondary deuterium isotope
      effect is observed on both kcat and kcat/Km. To investigate dependence on enzyme
      nucleophiles and proton donors, we have replaced eight potential catalytic
      residues with alanine by site-directed mutagenesis. Each FKBP variant efficiently
      catalyzes the PPIase reaction. Taken together, these data support an unassisted
      conformational twist mechanism with rate enhancement due in part to desolvation
      of the peptide bond at the active site. Fluorescence quenching of the buried
      tryptophan 59 residue by peptide substrate suggests that isomerization occurs in
      a hydrophobic environment.

PMID- 1371118
TI  - Positive and negative control of the skeletal alpha-actin promoter in cardiac
      muscle. A proximal serum response element is sufficient for induction by basic
      fibroblast growth factor (FGF) but not for inhibition by acidic FGF.
AB  - Like mechanical load in vivo, basic fibroblast growth factor (bFGF) selectively
      provokes cardiac expression of "fetal" genes including skeletal alpha-actin
      (SkA). Antithetically, acidic FGF (aFGF) suppresses SkA transcription. To define
      sites controlling SkA transcription in cardiac muscle cells, rat cardiac myocytes
      were transfected with internal-deletion and block-substitution mutations in the
      SkA promoter, including three motifs resembling the fos serum response element
      (SRE). The upstream, central, and proximal SREs each contributed to basal
      expression in cardiac myocytes. To determine whether identical elements mediate
      induction by bFGF versus inhibition by aFGF, the proximal SRE (SRE1) and fos SRE
      were positioned upstream from a neutral promoter. In cardiac myocytes, both the
      SRE1 and fos SRE were expressed at levels up to one-third that of the SkA
      promoter (nucleotides -202 to -11). Neither was expressed in quiescent cardiac
      fibroblasts. bFGF augmented SRE1-CAT activity, whereas aFGF produced no change;
      the fos SRE was induced by both. The transcriptional and mitogenic actions of
      aFGF were contingent on the presence of a putative nuclear translocation motif.
      Thus 1) the SkA SRE1 and fos SRE each suffice for tissue specificity in cardiac
      myocytes; 2) unlike the c-fos SRE, the SkA SRE1 is induced selectively by bFGF
      yet not aFGF; 3) sequences alternative or in addition to the SRE1 are obligatory
      for aFGF to suppress the SkA promoter; and 4) possible differences in
      intracellular localization are one basis for divergent actions of aFGF and bFGF
      in cardiac muscle cells.

PMID- 1371119
TI  - Structural and functional characterization of an inositol polyphosphate receptor
      from cerebellum.
AB  - An inositol polyphosphate receptor has been purified from bovine cerebellum which
      consists of three different polypeptides with Mr of 111,000, 102,000, and 52,000.
      Negative staining electron microscopy reveals globular-like structures 10-13 nm
      in diameter. The receptor has a Stokes radius of 400,000 daltons as determined by
      molecular sieve high performance liquid chromatography. The receptor preparation
      binds inositol 1,3,4,5-tetrakisphosphate, inositol hexaphosphate (or phytol), and
      inositol 1,4,5-trisphosphate (IP4, IP6, and IP3, respectively) with submicromolar
      affinity (0.19, 0.15, and 0.54 microM, respectively) at conditions approximating
      physiological ionic strength and pH. The purified receptor preparation, when
      reconstituted into planar bilayers, displays ion channel activity, preferentially
      permeable to K+. Permeability ratios of the channel are PK+/PNa+ approximately 5
      and PK+/PCl approximately 19. In symmetrical 100 mM KCl, the channel is
      characterized by long open times (minutes) with a conductance of 7.2 picosiemens.
      The channel is selectively modulated by IP4. That is, at 1 microM IP4, the mean
      open time decreased substantially to rapid flicker behavior and the channel is
      completely closed at 10 microM IP4. IP6 and IP3 did not modulate the channel
      under similar conditions. Thus, the channel appears to be an IP4-modulated K+
      channel.

PMID- 1371120
TI  - Hormone withdrawal triggers a premature and sustained gene activation from
      delayed secondary glucocorticoid response elements.
AB  - Glucocorticoid regulatory elements, denoted GREs and delayed secondary GREs
      (sGREs), bind the purified glucocorticoid receptors via distinctive sequence
      motifs and confer a primary and delayed secondary hormone inducibility,
      respectively, upon a linked reporter construct in stably transfected mammalian
      cells. The delayed secondary responses, but not the primary responses, are
      preceded by a time lag of several hours and blocked by protein synthesis
      inhibitors. In this report, we further characterized and distinguished these
      hormonal inductions. A 206-base pair DNA fragment from the hepatic rat alpha 2u
      globulin (RUG) gene, containing at least two delayed sGREs, was specifically
      activated by glucocorticoids in a dose-dependent manner via a process which is
      sensitive to receptor antagonist RU486. Delayed sGRE-stimulated production of
      correctly initiated transcripts was preceded by a time lag of 2 h, a time when
      the GRE-mediated induction had reached maximal levels. A pulse of glucocorticoids
      sustained maximal activation of the delayed secondary response but not the
      primary response. In fact, hormone withdrawal triggered a premature induction of
      this delayed secondary response, suggesting that delayed sGREs are under both
      negative and positive control of the hormone receptor. Two separable elements of
      the 206-base pair fragment, including the 29-base pair sequence of a single
      receptor binding site, activated the reporter expression as effectively with
      transient, pulsatile exposure to hormone as with continuous exposure. Our results
      suggest that the information content of a hormonal pulse is retained, or
      "memorized," more persistently by a receptor binding site of delayed sGREs than
      those of the prototypical GREs.

PMID- 1371122
TI  - Pediatric psychopharmacotherapy: a review of recent research.
AB  - In the past 5 years, we have witnessed the continuation of important trends in
      clinical research that began earlier in the decade. With regard to the treatment
      of specific disorders in children and adolescents, the most significant
      developments have been the examination of the tricyclics for the treatment of
      depression and the initiation of controlled studies for the treatment of Tourette
      syndrome. Unfortunately, the findings from the depression studies have been
      uniformly negative, and the results of research on both depression and tic
      disorders show a relatively high rate of placebo responsivity, which raises
      nagging questions about the role of case reports and open trials. Another
      important trend in pediatric psychopharmacotherapy is the search for substitutes
      for the neuroleptics. Potential candidates include agents such as lithium,
      naltrexone, fenfluramine, clonidine, and carbamazepine. The most underresearched
      disorders are a combination of the least common (e.g. schizophrenia, mania) and
      those that are apparently perceived as less serious (e.g. sleep disorders,
      certain anxiety disorders). Not surprisingly, the most studied disorder and
      treatment is hyperactivity and stimulant medication, respectively. Considerable
      progress has been made in understanding the social implications of the associated
      symptoms and their response to stimulant drugs, aided greatly by the use of
      direct observation procedures. Researchers are beginning to attend to the
      implications of comorbidity for assessing response to medication. There has been
      additional confirmation of efficacy of stimulant treatment for preschoolers and
      adolescents. Dose-response issues remain to some extent unresolved, the primary
      impediments being interpretive misconceptions associated with trend analysis, an
      overreliance on the syndromal perspective and too little attention to target
      behaviors and their clinical implications, and the failure to operationalize the
      minimal effective dose with regard to the normalization and supranormalization of
      target and collateral behaviors. Disagreement over whether hyperactivity is a
      learning or a behavior disorder (or both) and what academic underproductivity
      means clinically and socially is also impeding progress. With regard to
      developmental disorders, controlled studies indicate that fenfluramine and
      naltrexone are effective for managing associated symptoms in some individuals.
      However, given the limited amount of research on these agents, their status as
      clinically useful palliatives must be considered tentative.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1371121
TI  - Ligand-regulated internalization and recycling of human beta 2-adrenergic
      receptors between the plasma membrane and endosomes containing transferrin
      receptors.
AB  - Agonist-regulated redistribution of human beta 2-adrenergic receptors was
      examined in 293 cells. A specific antiserum recognizing the carboxyl-terminal
      hydrophilic domain of the receptor was developed, characterized, and used for
      immunocytochemical localization of receptors in fixed cells by conventional
      fluorescence and confocal fluorescence microscopy. The beta-adrenergic agonist
      isoproterenol induced redistribution of receptors from the surface of cells into
      small (less than 1 micron diameter) punctuate accumulations which were detected
      in cells within 2 min of agonist addition. The time course of receptor
      redistribution paralleled that of receptor sequestration measured by ligand
      binding, and receptor redistribution was reversible in the presence of the beta
      adrenergic antagonist alprenolol. Optical sections imaged through cells by
      confocal microscopy localized receptor accumulations within the cytoplasm. To
      address the question of receptor internalization further, a mutant receptor
      possessing an engineered antigenic epitope in the amino-terminal hydrophilic
      domain was constructed, transfected into cells, and localized using both a
      monoclonal antibody recognizing the epitope tag (receptor ectodomain) and an
      antiserum recognizing the carboxyl terminus (receptor endodomain). In untreated
      cells most receptor antigen was detected at the cell surface, as assessed by
      accessibility to ectodomain antibodies in unpermeabilized specimens. In
      isoproterenol-treated cells, however, little receptor antigen was detected at the
      cell surface. Punctate receptor accumulations present in isoproterenol-treated
      cells were labeled by antibodies only following permeabilization of cells, as
      expected if these receptor accumulations were intracellular. Finally,
      internalized beta-adrenergic receptors colocalized with transferrin receptors,
      which are markers of endosomal membranes. These data provide several lines of
      evidence establishing that beta-adrenergic receptors undergo ligand-regulated
      internalization, they suggest that internalized receptors may be recycled back to
      the cell surface, and they provide the first direct indication that these
      processes involve the same endosomal membrane system passaged by constitutively
      recycling receptors.

PMID- 1371123
TI  - Physicochemical and physiological properties of cholylsarcosine. A potential
      replacement detergent for bile acid deficiency states in the small intestine.
AB  - The properties of cholylsarcosine (the synthetic N-acyl conjugate of cholic acid
      with sarcosine [N-methylglycine]) were examined to determine its suitability as a
      bile acid replacement agent for conditions of bile acid deficiency in the small
      intestine, which causes fat malabsorption. Previous studies in rodents had shown
      that the compound was well transported by the liver and ileum and underwent
      neither deconjugation nor dehydroxylation during enterohepatic cycling. By 1H
      nuclear magnetic resonance, cholylsarcosine was found to exist in dilute aqueous
      solution as an almost equimolar mixture of two geometric isomers--cis and trans
      (around the amide bond)--in contrast to cholylglycine, which was present entirely
      in the trans form. The critical micellization concentration was 11 mmol/liter,
      similar to that of cholylglycine (10 mmol/liter). By nonaqueous titrimetry, the
      pKa' of cholylsarcosine was 3.7, only slightly lower than that of cholylglycine
      (3.9). Cholylsarcosine was poorly soluble below pH 3.7, but highly soluble above
      pH 4. In vitro, cholylsarcosine behaved as cholylglycine with respect to
      promoting lipolysis by lipase/colipase. There was little difference between
      cholylsarcosine and cholylglycine in their solubilization of an equimolar mixture
      of oleic acid, oleate, and monoolein (designed to simulate digestive products of
      triglyceride) or in their solubilization of monooleyl-glycerol alone. When a
      [3H]triolein emulsion with either cholylsarcosine or cholyltaurine was infused
      intraduodenally in biliary fistula rats, recovery of 3H in lymph was 52 +/- 10%
      (mean +/- SD) for cholylsarcosine and 52 +/- 11% for cholyltaurine. When perfused
      into the colon of the anesthetized rabbit, cholylsarcosine (5 mmol/liter) did not
      influence water absorption or permeability to erythritol, in contrast to
      chenodeoxycholate, which induced vigorous water secretion and caused erythritol
      loss. We conclude that cholylsarcosine possesses the physicochemical and
      physiological properties required for a suitable bile acid replacement in
      deficiency states.

PMID- 1371125
TI  - Binding of Pseudomonas cepacia to normal human intestinal mucin and respiratory
      mucin from patients with cystic fibrosis.
AB  - Although not as prevalent as Pseudomonas aeruginosa, Pseudomonas cepacia is
      another opportunistic pathogen which colonizes the lungs of at least some
      patients with cystic fibrosis. A subgroup of these patients exhibits the "cepacia
      syndrome", i.e., a rapid clinical deterioration and death within one year. To
      investigate potential early sites of bacterial attachment, we have measured the
      specific binding of P. cepacia isolates from cystic fibrosis (CF) sputa to both
      CF and non-CF mucins purified from respiratory and intestinal secretions,
      respectively. As shown in microtiter binding assays, clinical isolates from 19/22
      patients were found to bind to both mucins, with the highest specific binding
      exhibited by isolates from eight patients, seven of whom later died with the
      cepacia syndrome. No differences were observed in the binding capacity of the two
      (CF versus non-CF) mucins. Binding was specific, saturable, and not influenced by
      tetramethylurea, a disruptor of hydrophobic associations. Individual sugars were
      ineffective as hapten inhibitors, as were several lectins. Mucins treated by
      reduction/alkylation or chloroform/methanol extraction showed enhanced bacterial
      binding, findings which were attributed to exposure of underlying binding sites.
      Deglycosylation procedures indicated that mucin receptors for P. cepacia include
      N-acetylglucosamine and N-acetylgalactosamine, probably linked together as part
      of core oligosaccharide structures. P. cepacia isolates also bound to buccal
      epithelial cells, and mucin partially inhibited the binding of those isolates of
      P. cepacia that also had the ability to bind to mucin. We speculate that specific
      binding of P. cepacia to secreted mucins may be an early step in the pathogenesis
      of the cepacia syndrome.

PMID- 1371124
TI  - Basic fibroblast growth factor enhances the coupling of intimal hyperplasia and
      proliferation of vasa vasorum in injured rat arteries.
AB  - Basic fibroblast growth factor (bFGF) is mitogenic for smooth muscle cells (SMC)
      and angiogenic. We examined the in vivo effects of bFGF in balloon denuded
      carotid arteries of laboratory rats. bFGF was administered continuously from
      polymer-based devices at 34 ng/d into the periadventitial space of rat carotid
      arteries for 2 wk. Intimal hyperplasia was not observed in the absence of injury
      or with lipopolysaccharide induced endothelial dysfunction. Different degrees of
      vascular injury produced proportionally more intimal hyperplasia. bFGF increased
      the intimal hyperplastic response 1.3-fold with severe vascular injury, and 2.4
      fold with more mild injury. Increased cell proliferation, not extracellular
      matrix production, accounted for these effects. Cell density was unchanged for
      the control and bFGF-treated groups, and the number of proliferating intimal
      cells at 2 wk rose to an amount equivalent to the increase in mass; 1.9- and 4.0
      fold for severe and lesser injury, respectively. The relative ability of heparin
      to reduce SMC proliferation was not altered by the presence of bFGF.bFGF also
      induced profound angiogenesis within and surrounding the polymeric releasing
      device, and in the vasa vasorum immediately around the injured arteries. bFGF's
      effect on vasa was linearly related to the amount of SMC proliferation within the
      blood vessel. Thus, the in vivo mitogenic and angiogenic potential of bFGF are
      coupled, and may be similarly modulated by the products of local injury and/or
      factors in the vessel wall.

PMID- 1371126
TI  - Selective induction of rheumatoid factors by superantigens and human helper T
      cells.
AB  - Production of autoantibodies specific for the Fc region of autologous IgG, called
      rheumatoid factors (RF), is a characteristic finding in patients with rheumatoid
      arthritis (RA). To study the requirements regulating the synthesis of these
      autoantibodies, we have cloned human helper T cells and co-cultured them with
      purified B cells. To mimic cognate T-B cell interaction, we have used bacterial
      superantigens that function by cross-linking HLA molecules on the B cell with
      selected T cell receptor (TCR) molecules expressing a particular polymorphism of
      the V beta gene segment. Data presented here demonstrate that the staphylococcal
      enterotoxin D (SE D), but not other bacterial superantigens, exhibits an ability
      to induce IgM, IgG, and especially RF production, in B cells from RA patients and
      normal individuals. Comparison with the polyclonal antibody production in B cell
      cultures driven by anti-CD3-stimulated T cell clones confirmed that SE D shifted
      the repertoire of secreted antibodies toward immunoglobulins with Fc binding
      specificity, suggesting that SE D preferentially stimulates RF+ B lymphocytes. B
      cells with the potential to secrete RF were highly frequent in RA patients,
      requiring as few as 150 peripheral B cells/culture to detect RF in the culture
      supernatants. SE D-induced RF synthesis was strictly dependent on the presence of
      selected CD4+T helper cells and required a direct membrane contact between B
      cells and T helper cells. Here, we propose a model that SE D selectively induces
      RF production depending on the availability of SE D responsive T cells in the TCR
      repertoire of the responder.

PMID- 1371127
TI  - Human postnatal thymocytes generate phenotypically immature CD3dim, CD5dim,
      CD1abright progeny in organ culture.
AB  - We previously described an organ culture system that supports the in vitro
      development of human fetal thymocytes in murine alymphoid thymic rudiments
      without addition of exogenous factors. This approach to study human T cell
      precursors is limited by the requirement for fetal tissue. We show that human
      thymocytes from pediatric sources can be expanded under similar conditions. Organ
      cultures generated predominantly CD4 CD8 double positive cells, most of which
      maintained the phenotype CD3dim, CD5dim, and CD1abright, characteristic for
      double positive thymocytes ex vivo. This culture system should facilitate in
      vitro studies on human thymocyte development and repertoire selection.

PMID- 1371128
TI  - Cyclosporin A and FK506 mediate differential effects on T cell activation in
      vivo.
AB  - Modified limiting dilution analysis techniques were used to evaluate the effects
      of the immunosuppressants cyclosporin A (CsA) and FK506 on alloantigen-induced T
      cell activation in vivo. Treatment of sponge matrix allograft recipients with
      either CsA or FK506 inhibited lymphocytic infiltration of the allograft, a
      process thought to be dependent on local lymphokine production. In addition, both
      immunosuppressants markedly reduced the absolute number of lymphocytes recovered
      from the draining lymph nodes (LN) and prevented CTL activation in the LN.
      However, Ag-primed helper T lymphocytes (HTL) were present in the draining LN of
      sponge allograft recipients treated with CsA, but not in recipients treated with
      FK506. T cell depletion experiments were performed to determine the phenotype of
      primed HTL in the LN of untreated and CsA-treated sponge allograft recipients. In
      untreated sponge allograft recipients, CD4+ and CD8+ Ag-primed HTL were present
      in the draining LN in equivalent numbers. In contrast, the majority of primed HTL
      in the LN of CsA-treated sponge allograft recipients were CD8+, rather than CD4+
      T cells. These observations indicate that CsA and FK506 exert distinct in vivo
      effects at the level of HTL priming, and CD4+ and CD8+ HTL exhibit differential
      sensitivity to CsA in vivo.

PMID- 1371129
TI  - Antibody against the Leu-CAM beta-chain (CD18) promotes both LFA-1- and CR3
      dependent adhesion events.
AB  - The Leukocytic cell-adhesion molecule (beta 2 integrin) family of adhesion
      molecules play a key role in the intercellular adhesive interactions necessary
      for normal immune cell function. In this study, we report an antibody that
      recognizes an epitope on the Leukocytic cell-adhesion molecule common beta-chain
      (CD18) and promotes both lymphocyte function-associated Ag-1- and CR3-dependent
      adhesion events. The antibody recognizes a temperature-sensitive epitope that is
      not dependent on the presence of divalent cations. It is proposed that antibody
      binding promotes a conformational change in both lymphocyte function-associated
      Ag-1 and CR3, which may mimic a natural activation mechanism, resulting in
      increased cellular adhesion.

PMID- 1371131
TI  - Role of LFA-1 and VLA-4 in the adhesion of cloned normal and LFA-1 (CD11/CD18)
      deficient T cells to cultured endothelial cells. Indication for a new adhesion
      pathway.
AB  - Patients with the leukocyte adhesion deficiency (LAD) syndrome have a genetic
      defect in the common beta 2-chain (CD18) of the leukocyte integrins. This defect
      can result in the absence of cell surface expression of all three members of the
      leukocyte integrins. We investigated the capacity of T cell clones obtained from
      the blood of an LAD patient and of normal T cell clones to adhere to human
      umbilical vein endothelial cells (EC). Adhesion of the number of LAD T cells to
      unstimulated EC was approximately half of that of leukocyte function-associated
      antigen (LFA)-1+ T cells. Stimulation of EC with human rTNF-alpha resulted in an
      average 2- and 2.5-fold increase in adhesion of LFA-1+ and LFA-1- cells,
      respectively. This effect was maximal after 24 h and lasted for 48 to 72 h. The
      involvement of surface structures known to participate in cell adhesion
      (integrins, CD44) was tested by blocking studies with mAb directed against these
      structures. Adhesion of LFA-1+ T cells to unstimulated EC was inhibited (average
      inhibition of 58%) with mAb to CD11a or CD18. Considerably less inhibition of
      adhesion occurred with mAb to CD11a or CD18 (average inhibition, 20%) when LFA-1+
      T cells were incubated with rTNF-alpha-stimulated EC. The adhesion of LFA-1- T
      cells to EC stimulated with rTNF-alpha, but not to unstimulated EC, was inhibited
      (average inhibition, 56%) by incubation with a mAb directed to very late antigen
      (VLA)-4 (CDw49d). In contrast to LAD T cell clones and the LFA-1+ T cell line
      Jurkat, mAb to VLA-4 did not inhibit adhesion of normal LFA-1+ T cell clones to
      EC, whether or not the EC had been stimulated with rTNF-alpha. We conclude that
      the adhesion molecule pair LFA-1/intercellular adhesion molecule (ICAM)-1 plays a
      major role in the adhesion of LFA-1+ T cell clones derived from normal
      individuals to unstimulated EC. Adhesion of LFA-1-T cells to TNF-alpha-stimulated
      EC is mediated by VLA-4/vascular cell adhesion molecule (VCAM)-1 interactions.
      Since we were unable to reduce significantly the adhesion of cultured normal LFA
      1+ T cells to 24 h with TNF-alpha-stimulated endothelium with antibodies that
      block LFA-1/ICAM-1 or VLA-4/VCAM-1 interactions, and lectin adhesion molecule-1
      and endothelial leukocyte adhesion molecule-1 appeared not to be implicated,
      other as yet undefined cell surface structures are likely to participate in T
      cell/EC interactions.

PMID- 1371130
TI  - IL-4 induces adherence of human eosinophils and basophils but not neutrophils to
      endothelium. Association with expression of VCAM-1.
AB  - The present studies were performed to explore potentially selective mechanisms of
      leukocyte adhesion in an attempt to understand how preferential recruitment of
      eosinophils and basophils might occur during allergic and other inflammatory
      reactions. Stimulation of human vascular endothelial cells for 24 h with IL-4 (30
      to 1,000 U/ml) induced adhesion for eosinophils (up to approximately four-fold of
      control) and basophils (up to approximately twofold of control) but not
      neutrophils (less than 125% of control). Analysis of endothelial expression of
      adhesion molecules by flow cytometry revealed that IL-4 treatment induced
      vascular cell adhesion molecule-1 (VCAM-1) expression without significantly
      affecting the expression of other adhesion molecules, namely endothelial
      leukocyte adhesion molecule-1 (ELAM-1) or intercellular adhesion molecule-1 (ICAM
      1). The concentration-response curve for IL-4-induced VCAM-1 expression
      paralleled that for adhesion. Endothelial cells stimulated with IL-4 expressed
      adhesive properties for eosinophils by 3 h; the response increased steadily
      during a 24-h time course study. Eosinophils and basophils adhered to plates
      coated with a recombinant form of VCAM-1. This adhesion was blocked with
      antibodies to VCAM-1 but not ELAM-1. mAb directed against either VCAM-1 or VLA-4
      inhibited (by approximately 75%) the binding of eosinophils and basophils to IL-4
      stimulated endothelial cells. Because VLA-4 and VCAM-1 have been demonstrated to
      bind to each other in other adhesion systems, these results suggest that IL-4
      stimulates eosinophil and basophil adhesion by inducing endothelial cell
      expression of VCAM-1 which binds to eosinophil and basophil VLA-4. The lack of
      expression of VLA-4 on neutrophils and the failure of IL-4 to stimulate
      neutrophil adherence support this conclusion. It is proposed that local release
      of IL-4 in vivo in allergic diseases or after experimental allergen challenge may
      partly explain the enrichment of eosinophils and basophils (vs neutrophils)
      observed in these situations.

PMID- 1371132
TI  - Stimulation of human monocytes via CD45, CD44, and LFA-3 triggers macrophage
      colony-stimulating factor production. Synergism with lipopolysaccharide and IL-1
      beta.
AB  - Stimulation of human monocytes with immobilized mAb directed against the CD45,
      CD44, or LFA-3 Ag induced the production of macrophage-CSF (M-CSF). M-CSF
      specific transcripts appeared at 3 h poststimulation, were further increased by
      12 h, and were still detectable at 24 h. M-CSF gene expression was accompanied by
      the induction of small but detectable amounts of M-CSF protein. LPS and IL-1
      beta, but not IL-6 or TNF-alpha, dramatically augmented the ability of anti-CD45,
      anti-CD44, and anti-LFA-3 antibodies to induce M-CSF secretion but failed to
      stimulate M-CSF secretion in the absence of antibody. M-CSF activity in the
      culture supernatants was first detectable at 8 h of culture, peaked at day 2, and
      declined thereafter. Purified F(ab)2 fragments of anti-CD45 antibody were also
      effective in inducing M-CSF message and secretion, indicating that the Fc gamma
      RII is not involved in this response. Stimulation of cells with antibodies to the
      monocyte surface Ag MAC-1, LFA-1, and ICAM-1 did not result in M-CSF secretion.
      Moreover, LPS and IL-1 beta failed to synergize with these Ag in inducing M-CSF
      production. Together, these results indicate that stimulation of monocytes via
      the cell surface Ag CD45, CD44, and LFA-3 can trigger M-CSF production. However,
      second signals that can be provided by IL-1 beta or LPS are required to regulate
      optimal M-CSF protein secretion.

PMID- 1371133
TI  - Immunization with antigen bound to bispecific antibody induces antibody that is
      restricted in epitope specificity and contains antiidiotype.
AB  - Mice can be efficiently immunized in the absence of adjuvant using chemically
      cross-linked bispecific antibody (biAb) that bind to both class II MHC molecules
      and a protein Ag of interest. In our experiments, mice were immunized with the
      protein Ag hen egg lysozyme (HEL) bound to several different biAb, each of which
      contained a different mAb specific for a distinct (nonoverlapping) epitope of
      HEL. Primary and secondary serum antibody responses of the immunized mice were
      analyzed for their specificity for different epitopes of HEL. The results show
      that immunization with each HEL-biAb complex produced a bias in the epitope
      specificity of the primary antibody response. This bias was determined by the
      individual specificity of the anti-HEL mAb used in each biAb. The primary
      response was dominated by antibody reacting with epitopes distinct from that
      bound by the mAb in the immunizing complex, and was deficient in antibody that
      recognized the epitope bound by the biAb during immunization. This bias in
      antibody specificity was maintained during the secondary antibody response that
      followed a single challenge with soluble HEL alone. However, an additional
      challenge with HEL induced a switch in the specificity pattern, with increased
      amounts of antibody against the epitope that was previously ignored. In addition,
      immunization with Ag bound to biAb resulted in a substantial primary anti-Id
      response, detected by serum antibody specific only for the Fab'2 fragment of the
      mAb used in the biAb. These studies illustrate two unique features of
      immunization using biAb that allow for fine manipulation of the epitope
      specificity and anti-Id repertoires of the antibody response to whole protein Ag.

PMID- 1371134
TI  - Comparative study of the T cell response to two allelic forms of a malarial
      vaccine candidate protein.
AB  - T cell responses to two allelic forms of the merozoite surface Ag 2 (MSA2) of
      Plasmodium falciparum were mapped in mice using the rMSA2 proteins, Ag 1609 which
      has the sequence of the FCQ27/PNG strain and Ag 1615 which has the sequence of
      the Indochina 1 strain. Lymph node cells of BL/10 and B10.BR mice immunized with
      either Ag 1609 or Ag 1615 responded to both Ag in in vitro proliferation assays.
      Lymph node cells of BALB/c mice did not respond. The T cell determinants
      recognized by the responder strains were mapped to conserved and variant regions
      of these Ag using overlapping synthetic peptides. The determinants recognized by
      each mouse strain were distinct. Marked difference in sequence between the
      central regions of the two rMSA2 proteins did not affect antigenic processing of
      the conserved N and C terminal regions. Hence lymph node cells of BL/10 mice
      immunized with either Ag 1615 or Ag 1609 recognized an immunodominant T cell
      determinant at the highly conserved N terminal end within the sequence
      YSNTFINNAYNMSIR (peptide 3b) and B10.BR mice similarly immunized recognized an
      immunodominant determinant at the highly conserved C terminal within the sequence
      CTDGNKENCGAATSL (peptide 23). Several peptides identified as containing
      immunodominant T cell determinants specific to BL/10 mice induced peptide
      specific T cells in both BL/10 and B10.BR mouse strains when used as immunogens.
      However, the ability of the peptide-primed T cells to proliferate in response to
      the rMSA2 proteins was confined to BL/10 mice. An example of this was observed
      with peptides 3b and N (KNESKYSNTFINNAYNMSIRRSMAN). Peptide N was able to prime
      B10.BR and BL/10 mice for an enhanced antibody response when these mice were
      subsequently immunized with Ag 1615 even though Ag 1615-specific T cell
      proliferation was not detected in B10.BR mice primed with N. The study concluded
      that 1) conserved sequences such as peptide N when used in vaccines may give rise
      to MSA2-specific memory Th cells amenable to boosting by subsequent exposure to
      all parasite strains and 2) peptide priming may be a useful pathway for inducing
      defined memory Th cells in a wider population and for preferentially inducing T
      dependent over T independent responses to some malarial Ag.

PMID- 1371135
TI  - Activation of cytokine genes in HIV-1 infected myelomonoblastic cells by phorbol
      ester and tumor necrosis factor.
AB  - The differential production of inflammatory cytokines (IL-1 alpha, IL-1 beta, IL
      6, and TNF-alpha) was analyzed in the PLB-985 myelomonoblastic cell line,
      chronically infected or not by the IIIB strain of HIV-1. After treatment with
      phorbol ester (PMA) or TNF-alpha, a 20- to 40-fold increase in the level of IL-1
      beta mRNA was observed in the HIV-infected PLB-IIIB as compared with the parental
      PLB-985 cells. The majority of the IL-1 beta activity detected in both cell types
      remained cell associated. In contrast, TNF-alpha mRNA levels were increased in
      both infected and uninfected cells; the t1/2 of TNF RNA was 90 min in uninfected
      cells and 30 min in HIV-infected cells. Interestingly, about 14-fold more TNF
      activity was secreted from PLB-IIIB than from similarly stimulated PLB-985 cells,
      indicating an enhanced translational efficiency of TNF RNA in PLB-IIIB cells. The
      PMA- or TNF-induced levels of IL-1 alpha mRNA did not vary significantly between
      the two cell types whereas IL-6 was poorly inducible in both cells. These results
      illustrate a differential cytokine response to HIV-1 infection in myeloid cells
      and demonstrate that HIV-1 infection of myelomonoblastic cells may alter both
      transcriptional and translational mechanisms controlling cytokine expression.

PMID- 1371136
TI  - The cDNA structure, expression, and chromosomal assignment of the mouse Fas
      antigen.
AB  - The cell surface Fas antigen is a membrane-associated polypeptide which can
      mediate apoptosis. cDNA clones encoding the Fas antigen were isolated from a cDNA
      library constructed with mRNA from the mouse macrophage cell line BAM3. The
      nucleotide sequence and the deduced amino acid sequence of the mouse Fas antigen
      were 58.5 and 49.3% identical, respectively, to the corresponding sequences of
      human Fas antigen cDNA. The mouse Fas antigen consists of 306 amino acids with a
      calculated Mr of 34,971 and contains a single transmembrane domain which divides
      the molecule into extracellular and cytoplasmic domains. A 2.1-kb mRNA coding for
      the Fas antigen was detected in the mouse thymus, heart, liver, and ovary but not
      in brain and spleen. The expression of the Fas antigen gene in mouse fibroblast
      L929 and macrophage BAM3 cell lines was significantly induced by treatment with
      IFN-gamma but not by IFN-alpha/beta. Interspecific backcross analysis indicated
      that the gene coding for the Fas antigen is in the distal region of mouse
      chromosome 19.

PMID- 1371137
TI  - Peptide-presenting similarities among functionally distant HLA-B27 subtypes
      revealed by alloreactive T lymphocytes of unusual specificity.
AB  - Functional dissection of HLA-B27 subtypes using alloreactive or B27-restricted
      CTL has shown that the structurally related B*2704 and B*2706 are the most
      distant subtypes relative to the prototype B*2705. In particular, previous
      studies have failed to find anti-B*2705 CTL cross-reacting with B*2704 or B*2706.
      Such failure can be accounted for by the drastic effect on T cell recognition of
      the change at residue 152 in both subtypes relative to B*2705, as established
      with site-directed mutants. B*2704 and B*2706 are also related in ethnic
      distribution, as they are restricted to Orientals, jointly being the predominant
      HLA-B27 subtypes in this population. As far as it is known, there are no
      differences relative to B*2705 in their linkage to ankylosing spondylitis. In our
      study, 5 of 13 examined anti-B*2705 limiting dilution CTL lines from a particular
      HLA-B27- individual were shown to crossreact with B*2704, B*2706 or both. The
      monoclonal nature of this cross-reaction was established by cold target
      competition analysis. This result demonstrates that the apparent differences in T
      cell antigenicity among anti-B27 subtypes are strongly influenced by the
      responder individual, as the spectrum of clonal specificities in anti-B27
      responses may show significant differences among unrelated responders. Fine
      specificity differences among the cross-reactive CTL allowed unambiguous
      functional distinction between B*2704 and B*2706. The molecular basis of such
      cross-reactivity was examined by correlating CTL reaction patterns with the
      structure of both subtypes, which differ only by two residues located in the beta
      pleated sheet bottom of the peptide binding site, and with site-directed mutants
      mimicking HLA-B27 subtype polymorphism. The results suggest that: 1) distinct
      peptides are involved in the allospecific epitopes recognized by the various
      crossreactive CTL, and 2) B*2704, B*2706, and B*2705 differ in their peptide
      presenting specificity, but can present some identical or structurally similar
      peptides.

PMID- 1371138
TI  - The role of insulin-like growth factor-I and insulin-like growth factor-binding
      protein-1 in the control of human fetal growth.

PMID- 1371139
TI  - Analgesic use in home hospice cancer patients.
AB  - BACKGROUND: Pain control in hospice patients in the home may be compromised by
      concerns about overuse of analgesics, particularly narcotics. METHODS: A
      retrospective chart audit of analgesic type and amount was performed on the
      medical records of 100 cancer patients receiving hospice care in the home.
      Different types and amounts of analgesics were converted to a common standard, an
      oral morphine equivalent (OME) relative to 1 mg of oral morphine sulfate.
      Descriptive statistics were used to characterize patient analgesic use during the
      entire course of hospice care and the last 5 days of life. Associations between
      analgesic use and select patient characteristics (age, sex, cancer site,
      metastases, and pain intensity at admission) were explored. RESULTS: Ninety-one
      percent of the sample had used analgesics at some time during hospice care. The
      proportion of patients using analgesics increased as death approached. The mean
      and median daily analgesic use over the entire period were 114 and 82 OMEs and
      during the last 5 days 140 and 84 OMEs, respectively. The range of mean daily
      analgesic use was between 10 and 735 OMEs. CONCLUSIONS: Individual variability in
      analgesic use was demonstrated. Not all patients required analgesics, and among
      those who did there was remarkable variation in the amount used. Large and even
      enormous doses of analgesics may sometimes be required to control cancer pain.

PMID- 1371140
TI  - Care of cancer patients in a home-based hospice program: a comparison of
      oncologists and primary care physicians.
AB  - BACKGROUND: The purpose of this study was to describe a group of patients cared
      for in a home-based hospice program and to determine if there was a difference in
      patients' experiences dependent on whether the attending physician was a primary
      care physician or an oncologist. METHODS: Information about cancer patients
      admitted to the Burlington Visiting Nurse Association (VNA) Hospice program from
      January 1986 to December 1990 was reviewed to compare the experiences of the
      patients of the oncologists with those of the patients of the primary care
      physicians. RESULTS: There was no difference in average length of stay or overall
      ambulatory status between the patient groups. The patient group cared for by
      oncologists had more hospitalizations than the group cared for by primary care
      physicians though there was not a significant difference in the percentage of
      hospital vs home deaths. There was a significant difference between the groups in
      the use of controlled-release morphine, with oncologists using this approach more
      often than primary care physicians. Oncologists also had more patients on
      continuous parenteral morphine infusions during hospice care. CONCLUSIONS:
      Primary care physicians as well as oncologists provide effective cancer care and
      pain control in this home-based hospice program. The hospice interdisciplinary
      team can be a valuable resource for physicians in supplying information on
      appropriate narcotics dosages and routes of administration for their dying
      patients.

PMID- 1371141
TI  - Use of latex agglutination testing in diagnosing pediatric meningitis.
AB  - BACKGROUND: Latex agglutination (LA) tests are ordered frequently on cerebral
      spinal fluid (CSF) specimens obtained from pediatric patients to identify
      pathogenic bacteria as early as possible in an acute infection. METHODS: Six
      hundred ten LA tests were performed on 176 patients suspected of having
      meningitis. RESULTS: Five patients with meningitis had positive LA tests. We
      found that the CSF white blood cell (WBC) count, and differential were the best
      predictors of meningitis. CONCLUSIONS: By limiting the use of LA tests to those
      patients having CSF with abnormal WBC counts or with positive Gram stains, the
      number of tests ordered would have been reduced. This practice would greatly
      reduce laboratory expense.

PMID- 1371142
TI  - Chronic pain beyond patienthood.
AB  - Forty nonconsumers (subjects with pain lasting for more than 1 year who had not
      consulted a doctor because of it during the preceding year) were compared with 46
      chronic patients at a pain clinic. The mean duration of the nonconsumers' pain
      was twice as long as that of the patients'. Although their pain intensity, as
      assessed with pain diaries, did not differ, their estimated pain intensity was
      less than that of the pain patients; they took fewer analgesics, were less
      functionally impaired, made less use of coping strategies associated with poor
      adjustment, were less depressed, and expected less help from external resources.
      The "non-consumer attitude" appears to be independent of the duration of the pain
      complaints.

PMID- 1371143
TI  - Target-dependent regulation of retinal nicotinic acetylcholine receptor and
      tubulin RNAs during optic nerve regeneration in goldfish.
AB  - A fundamental issue in central nervous system development regards the effect of
      target tissue on the differentiation of innervating neurons. We address this
      issue by characterizing the role the retinal ganglion cell target, i.e., the
      optic tectum, plays in regulating expression of tubulin and nicotinic
      acetylcholine receptor genes in regenerating retinal ganglion cells. Tubulins are
      involved in axonal growth, whereas nicotinic acetylcholine receptors mediate
      communication across synapses. Retinal ganglion cell axons were induced to
      regenerate by crushing the optic nerve. Following crush, there was a rapid
      increase in alpha-tubulin RNAs (3 days), which preceded the increase in nicotinic
      acetylcholine receptor RNAs (10-15 days). Both classes of RNAs approached control
      levels by the time retinotectal synapses and functional recovery were restored (4
      6 weeks). If the optic nerve was repeatedly crushed or its target ablated,
      tubulin RNAs remained elevated, and the increase in receptor RNAs that would
      otherwise be seen 2 weeks after a single nerve crush did not occur. The
      interaction of retinal ganglion cell axons with their targets in the optic tectum
      appears, then, to exert a suppressive effect on the RNA encoding a cytoskeletal
      protein, tubulin, and an inductive effect on RNAs encoding nicotinic
      acetylcholine receptors involved in synaptic communication.

PMID- 1371144
TI  - Steroid inhibition of neural microvessel morphogenesis in vitro: receptor
      mediation and astroglial dependence.
AB  - Steroid hormones alter several aspects of microvascular function within the CNS.
      Both microvessel formation and blood-brain barrier expression appear to be
      influenced by interactions between astrocytes and endothelial cells. To determine
      if steroids alter astrocyte-endothelial interactions, we studied their effects on
      astroglial-induced microvessel morphogenesis in vitro. C6 astroglial cells induce
      bovine retinal microvascular endothelial cells to differentiate into capillary
      like structures. Dexamethasone, hydrocortisone, and progesterone at 10 nM
      inhibited C6-induced microvessel morphogenesis by 75, 35, and 30%, respectively.
      Inhibition by dexamethasone was both time and concentration dependent, reaching
      80-100% at 1 microM. Tetrahydrocortisone and 17 alpha-hydroxyprogesterone had
      only marginal inhibitory effects. Cortexolone, a glucocorticoid receptor
      antagonist, blocked inhibition by dexamethasone. Progesterone receptors were
      expressed in C6 but not bovine retinal microvascular endothelial cells,
      identifying the astroglial cell as the likely effector of progesterone-mediated
      inhibition. Astroglial cells were further implicated as the effectors of steroid
      mediated inhibition because none of the steroids inhibited astroglial-independent
      capillary-like structure formation in response to a reconstituted extracellular
      matrix, Matrigel. These findings are evidence that steroids modulate neural
      microvascular endothelial cell functions indirectly through perivascular
      astrocytes via a receptor-mediated mechanism.

PMID- 1371145
TI  - Temporal expression of HNK-1-reactive sulfoglucuronyl glycolipid in cultured
      quail trunk neural crest cells: comparison with other developmentally regulated
      glycolipids.
AB  - Monoclonal antibody HNK-1 is an important marker for embryonic neural crest cells
      and some of their differentiated derivatives. We have identified 3
      sulfoglucuronylneolactotetraosylceramide (SGGL-1) as one of the HNK-1 antigens
      present in cultures of trunk neural crest cells. This lipid was present at 2 days
      in vitro and increased in amount with time in culture. Other major HNK-1-reactive
      antigens present in the culture were glycoproteins of apparent molecular masses
      of 120, 180, and 200 kDa. The 180- and 200-kDa bands were present at 2, 7, and 17
      days in vitro, whereas the 120-kDa band was present only at 17 days in vitro.
      Gangliosides GD3, LD1, and LM1 were also found in the cultures and exhibited
      distinct temporal patterns of expression. Ganglioside GD3 was present at all
      stages examined and its expression peaked at 7 days in vitro. In contrast, LD1
      was present only at 2 days in vitro and was not detectable at later times.
      Ganglioside LM1 increased in amount with time in culture in a pattern similar to
      that seen for SGGL-1. Taken together, these results indicate that several HNK-1
      reactive molecules are expressed in neural crest cultures in a temporally
      regulated manner along with several glycolipids that do not bear this epitope.

PMID- 1371147
TI  - Expression of size-selected RNA encoding brain serotonin transporter in Xenopus
      laevis oocytes.
AB  - The mRNA that encodes a serotonin transporter was expressed using the Xenopus
      laevis oocyte expression system. Poly(A)+ RNA isolated from mouse brainstem was
      injected into Xenopus laevis oocytes, and the ability of oocytes to take up
      serotonin was measured 3 days postinjection. RNA-dependent serotonin uptake was
      sensitive to citalopram, a specific inhibitor of serotonin uptake, whereas
      background levels of serotonin uptake were not citalopram sensitive. Two RNA size
      fractions, 4.0 and 4.5 kb, were most efficient in stimulating uptake. Injection
      into Xenopus laevis oocytes of the 4.5-kb size fraction of mouse brainstem RNA
      resulted in threefold more serotonin uptake than did injection of unfractionated
      poly(A)+ RNA.

PMID- 1371146
TI  - Biochemical characterization and localization of a non-N-methyl-D-aspartate
      glutamate receptor in rat brain.
AB  - The structure and distribution of non-N-methyl-D-aspartate glutamate receptors in
      the rat brain were studied using subunit-specific antibodies that recognize the
      receptor subunit GluR1. The GluR1 protein, a 106-kDa glycoprotein, appears
      predominantly in synaptic plasma membranes, where it is highly enriched in the
      postsynaptic densities. When synaptic plasma membranes are solubilized with the
      detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, high
      affinity alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) binding and
      GluR1 immunoreactivity comigrate at a native Mr of 610,000. GluR1 is enriched in
      the hippocampus and cerebellar cortex but is present throughout the CNS. It is
      found on neuronal cell bodies and processes within most regions of the brain;
      within the cerebellum, however, it is localized to the Bergmann glia. These data
      suggest that the GluR1 protein is a subunit of multimeric AMPA-preferring
      glutamate receptors present on neurons and on specialized glia.

PMID- 1371148
TI  - Characterization of substance P-like immunoreactivity and tachykinin-encoding
      mRNAs in rat medullary thyroid carcinoma cell lines.
AB  - Rat thyroid tissue and three rat medullary thyroid carcinoma cell lines, 6-23,
      WE4/2, and CA77, have been examined for substance P (SP) and SP-like peptide
      expression. Analysis by combined HPLC and radioimmunoassay revealed the presence
      of SP in thyroid and 6-23 cell extracts. The presence of SP-encoding mRNAs was
      also detected in 6-23 cells by solution hybridization-nuclease protection
      analysis. SP-encoding mRNA expression was increased (fourfold) by maintaining the
      6-23 cells in low serum (2%) for 4 or 10 days. The 6-23 cells also expressed
      other SP-like immunoreactive species, which were chromatographically and
      immunologically distinct from established tachykinin peptides. WE4/2 cells did
      not contain SP but did display SP-like immunoreactivity (SPLI), which migrated
      like the unidentified SPLI in 6-23 cells. CA77 cells did not contain SP or SP
      encoding mRNA but did contain SPLI that migrated identically to the unidentified
      SPLI in the other cell lines. This novel SPLI was detected with an antiserum
      directed against the SP carboxyl terminus and to a lesser extent with an
      antiserum directed against the neurokinin A carboxyl terminus, but it showed
      minimal cross-reactivity using an antiserum directed against the midportion of
      SP. Treatment with 50 mM KCl resulted in secretion of this SPLI from CA77 cells.
      Gel filtration analysis demonstrated that this novel SPLI had an apparent
      molecular weight of approximately 1,000. These results are discussed in terms of
      cell lines that express tachykinin peptides and in terms of the molecular nature
      of the new SPLI detected in CA77 cells.

PMID- 1371149
TI  - Comparison of the N-linked oligosaccharide structures of the two major human
      myelin glycoproteins MAG and P0: assessment and relative occurrence of
      oligosaccharide structures by serial lectin affinity chromatography of 14C
      glycopeptides.
AB  - The N-linked oligosaccharide structures of human myelin-associated glycoprotein
      (MAG) and P0 have been characterized by serial lectin affinity chromatography
      (SLAC) of 14C-glycopeptides. 14C-Glycopeptides were prepared from purified MAG
      derivative and P0 by extensive proteolytic digestion and N-14C-acetylation.
      Assuming that all the 14C-glycopeptides were radiolabelled to the same specific
      radioactivity, the relative occurrence of the oligosaccharide structures was
      correlated to the amount of incorporated radioactivity. Sixteen and 15 fractions
      were generated by SLAC of MAG and P0 14C-glycopeptides, respectively. Despite
      this tremendous structural heterogeneity, the oligosaccharide "fingerprints" of
      MAG and P0 obtained by SLAC displayed similarities: (a) of the three types of N
      linked oligosaccharides, the complex type accounted for 80.4% and 94.9% of MAG
      and P0 radioactivity, respectively; (b) biantennary complex oligosaccharides were
      the major structures present on MAG and P0; (c) approximately 60% of MAG and P0
      oligosaccharides possessed a bisecting N-acetylglucosamine residue; and (d) large
      amounts of oligosaccharides with an alpha(1-6)fucose residue were found in both
      MAG and P0 and, noticeably, approximately 25% of the tri- and/or tetraantennary
      and approximately 90% of the bisected biantennary oligosaccharides of both
      glycoproteins contained alpha(1-6)fucose residues in the core. This study
      demonstrates that MAG and P0, both belonging to the immunoglobulin superfamily,
      display structural similarities in their N-linked oligosaccharide contents.

PMID- 1371150
TI  - Comparison of the N-linked oligosaccharide structures of the two major human
      myelin glycoproteins MAG and P0: assessment of the structures bearing the epitope
      for HNK-1 and human monoclonal immunoglobulin M found in demyelinating
      neuropathy.
AB  - The epitope for HNK-1 and patient's monoclonal autoantibodies in demyelinating
      polyneuropathy associated with immunoglobulin M gammopathy is borne by different
      types of N-linked oligosaccharide structures in human P0 and myelin-associated
      glycoprotein (MAG). Fourteen glycopeptide fractions bearing different
      oligosaccharide structures were obtained from either MAG or P0 glycopeptides by
      serial lectin affinity chromatography on concanavalin A-Sepharose, Phaseolus
      vulgaris erythrophytohemagglutinin-agarose, Pisum sativum agglutinin-agarose, and
      Phaseolus vulgaris leucophytohemagglutinin-agarose. As shown by dot-TLC plate
      immunostaining, the same MAG and P0 glycopeptide fractions were recognized by HNK
      1 and patient's immunoglobulin M, confirming that these antibodies display
      similar specificities. The antigenic carbohydrate was present in glycopeptide
      fractions that either interact with Pisum sativum agglutinin-agarose or were
      bound by Aleuria aurantia agglutinin-digoxigenin, indicating that these
      structures contained alpha(1-6)fucose residues. This study demonstrates that the
      L2/HNK-1 epitope is borne mainly or even exclusively by N-linked oligosaccharide
      structures alpha(1-6)fucosylated in the core.

PMID- 1371151
TI  - c-fos expression as a model for studying the action of hexachlorocyclohexane
      isomers in the CNS.
AB  - The induction of protooncogene c-fos in the CNS after administration of several
      convulsants has been studied. The organochlorine insecticide gamma
      hexachlorocyclohexane (gamma-HCH, lindane) has been shown to induce c-fos
      expression in different brain areas. Pentylenetetrazole and picrotoxin, a known
      gamma-aminobutyric acid-receptor antagonist, have also been considered. The
      administration of two nonconvulsant isomers of gamma-HCH, alpha-HCH, and delta
      HCH, before the mentioned toxicants, affects the protooncogene expression in
      different ways. The differential pattern of expression displayed by c-fos after
      these treatments suggests the presence of diverse mechanisms of action for the
      compounds studied.

PMID- 1371153
TI  - Tau 2: a probe for a Ser conformation in the amino terminus of tau.
AB  - We have determined the epitope for Tau 2, a monoclonal antibody that intensely
      stained tangles, plaque neurites, and curly fibers in the tissue section, and
      strongly labeled bovine tau, but only very weakly labeled human tau on the blot.
      The epitope has been localized to Ala95 through Ala108 of bovine tau. Ser101 is
      critical for Tau 2 reactivities; the replacement of Ser by Pro, which is found in
      rat, mouse, and human tau, brings about very weak Tau 2 reactivities. The strong
      Tau 2 staining of tangles and its effective absorption with a synthetic Ser
      peptide (Ala95 through Ala108) suggest that the tau in paired helical filaments
      takes a Ser conformation, rather than a Pro conformation, in its amino-terminal
      portion.

PMID- 1371152
TI  - In vivo neurochemical evaluation of striatal serotonergic hyperinnervation in
      rats depleted of dopamine at infancy.
AB  - Destruction of nigrostriatal dopamine (DA) neurons with 6-hydroxydopamine (6
      OHDA) early in development results in hyperinnervation of striatum by the
      serotonergic afferents deriving from the dorsal raphe nucleus. We have used in
      vivo microdialysis to investigate the degree to which serotonergic
      neurotransmission in striatum is altered by this increase in the density of
      serotonin (5-HT) terminals. The effects of several manipulations known to
      influence 5-HT function on extracellular 5-HT and 5-hydroxyindoleacetic acid in
      striatum were compared in adult rats treated neonatally with 6-OHDA and in intact
      adult rats. Basal levels of 5-HT in extracellular fluid (ECF) of striatum were
      similar in neonatally DA-depleted rats and in intact rats. Perfusion with the 5
      HT reuptake blocker, fluoxetine (100 microM), increased 5-HT in striatal ECF of
      neonatally DA-depleted rats to levels that were threefold greater than those
      achieved in intact rats. Likewise, K(+)-depolarization of the 5-HT terminals (100
      mM in perfusate) or systemic administration of the 5-HT releaser, (+/-)
      fenfluramine (10 mg/kg i.p.), increased the concentration of 5-HT in striatal ECF
      of neonatally DA-depleted rats to levels approximately threefold greater than
      those observed in striatum of intact rats. These findings indicate that the 5-HT
      hyperinnervation of striatum that takes place in rats depleted of DA at infancy
      is associated with an increased capacity for neurotransmitter release in this
      system. Concomitant increased in high-affinity 5-HT uptake may prevent the
      occurrence of any measurable changes in the resting concentration of 5-HT in
      striatal ECF.

PMID- 1371154
TI  - Detection of multisulphated N-linked glycans in the L2/HNK-1 carbohydrate epitope
      expressing neural adhesion molecule P0.
AB  - P0, the most abundant glycoprotein of PNS myelin, is a homophilic and
      heterophilic adhesion molecule. P0 is known to contain a glycoform population
      that expresses the L2/HNK-1 carbohydrate epitope found on other neural adhesion
      molecules, and to be functionally implicated centrally in neural cell adhesion
      and neurite outgrowth. This carbohydrate epitope has been characterized
      previously from glycolipid structures and contains a sulphated glucuronic acid
      residue. However, the L2/HNK-1 carbohydrate epitope has not been characterized in
      glycoproteins. Because P0 possesses only one glycosylation sequon, the number of
      P0 glycoforms is equal to the heterogeneity of the glycan species. Here we report
      that the carbohydrate analysis of L2/HNK-1-reactive P0 showed the presence of
      anionic structures containing sialic acid and sulphate in various combinations.
      At least one sulphate residue was present in 80% of the monosaccharide sequences,
      and 20% contained three sulphates. High-resolution P4 gel chromatography of the
      desialylated and desulphated oligosaccharides showed substantial heterogeneity of
      monosaccharide sequences. Sequential exoglycosidase digestions indicated that the
      majority of the structures were of the hybrid class, although the sulphated
      structures were found to be endoglycosidase H-resistant.

PMID- 1371155
TI  - Immunocytochemical localization of the L1 and N-CAM cell adhesion molecules and
      their shared carbohydrate epitope L2/HNK-1 in the developing and differentiated
      gustatory papillae of the mouse tongue.
AB  - The localization of the cell adhesion molecules L1 and N-CAM, and their shared
      carbohydrate epitope L2/HNK-1, was investigated at the light and electron
      microscopic levels in developing and adult fungiform and circumvallate gustatory
      papillae of the mouse tongue. At embryonic day 13, the earliest stage
      investigated, the tongue epithelium was still undifferentiated and was not yet
      innervated by sensory fibres. At this stage none of the three molecules was
      detectable within the tongue epithelium. At embryonic day 15 the primordia of the
      gustatory papilla became unequivocally discernible when the papillary epithelium
      was already innervated by few sensory axons. At this stage N-CAM was the first
      molecule expressed on epithelial cells and was confined to those parts of the
      papillary epithelium destined to become the chemosensory cells of the taste buds.
      The sensory axons were N-CAM-, L1- and L2/HNK-1-positive when fasciculating or
      contacting their accompanying Schwann cells or the cells of the papillary
      epithelium. Contacts between Schwann cells were also prominently labelled by
      antibodies to the three antigens. The mesenchymal tissue underlying the
      prospective sensory epithelium expressed N-CAM at all embryonic stages, but
      ceased to be N-CAM positive within the first six postnatal days. From embryonic
      day 16 onward a weak L1 immunoreactivity was detectable within the basal and
      intermediate layers of the lingual epithelium and remained present in adulthood.
      Cytodifferentiation of epithelial cells into spindle-shaped sensory cells and
      organization into taste buds began at postnatal day two. Simultaneously, L1 and
      L2/HNK-1 immunoreactivity increased on taste bud cells and N-CAM disappeared from
      the non-sensory extragemmal parts of the papillary epithelium. At approximately
      postnatal day six, taste bud formation was complete and the pattern of cell
      adhesion molecule expression was comparable to that found in the adult in that L1
      was strongly expressed on the apposing surfaces of all cells, whereas N-CAM was
      confined to cell contacts between a subpopulation of intragemmal cells. The
      L2/HNK-1 epitope was visible on the surfaces of taste bud cells, on intragemmal
      axons, and in a small portion of extracellular matrix directly underlying the
      taste buds, but was no longer expressed on those parts of the sensory fibres
      embedded in the subepithelial mesenchyme. The L2/HNK-1 epitope may thus be
      regarded as a cell surface marker for the cellular elements of mature taste buds.
      The highly sialylated form of N-CAM was not detectable at any stage
      investigated.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1371156
TI  - Cysteine proteinases from Schistosoma haematobium adult worms.
AB  - To identify and characterize cysteine proteinases from Schistosoma haematobium,
      lyophilized adult worms were homogenized, and enzymes were isolated and purified.
      From extracts prepared in acidic buffer, 3 putative cysteine proteinases were
      identified either directly or indirectly. The first proteinase (ShCP1) was
      identified by labeling with a radioiodinated inhibitor, Z-Tyr-Ala-CHN2, as a 35
      kDa protein. However, it could not be detected by silver staining, amino acid
      sequencing, or by a monoclonal antibody specific for a similar molecule from
      Schistosoma mansoni. A second cysteine proteinase, ShCP2, was purified by gel
      filtration and dialysis. This 32-kDa molecule was thiol-dependent and was labeled
      with Z-Tyr-Ala-CHN2. The amino terminal amino acid sequence of ShCP2 showed
      remarkable similarity (up to 77%) to that of S. mansoni cathepsin B (SmCP2) as
      well as to mammalian cysteine proteinases. Both ShCP1 and ShCP2 reacted with
      polyclonal antibodies against S. mansoni, suggesting the existence of shared
      antigenic epitopes. A third activity, ShCP3, was identified as possibly a
      distinct proteinase based on its similarities to a 28-kDa cysteine proteinase
      from S. mansoni. This preliminary investigation demonstrates that the overall
      profile of cysteine proteinases in S. haematobium is very similar to that of S.
      mansoni.

PMID- 1371157
TI  - Nonspecific oral immunity in individuals with HIV infection.
AB  - Lactoferrin, lysozyme, interferon, and neopterin levels were determined in
      parotid saliva from 44 individuals with different clinical stages of human
      immunodeficiency virus (HIV) infection and 19 HIV-seronegative controls. The
      secretory output of individual components was calculated according to the fluid
      flow rate. No parotid interferon activity was found in any of the HIV-infected
      subjects or controls, and no significant differences in parotid lysozyme or
      neopterin outputs were observed. The lactoferrin output was significantly
      decreased in HIV-seropositive subjects in parallel with their markedly reduced
      parotid secretory IgA output. This combined deficiency of parotid lactoferrin and
      secretory IgA may well contribute to the frequent oral infections seen in
      subjects with HIV infection.

PMID- 1371158
TI  - Cyclosporine and FK506 inhibition of murine mast cell cytokine production.
AB  - The ability of cyclosporine (CSA) and FK506 to inhibit cytokine production by
      factor-dependent murine mast cell lines was investigated. The mast cell clone,
      MC/9, and two mast cell lines, MCIII and MCVI, were stimulated to produce
      cytokines with phorbol myristate acetate plus the calcium ionophore A23187. The
      production of cytokines by stimulated mast cells cultured in the presence or
      absence of drug was monitored by bioassay of culture supernatants for induction
      of proliferation by factor-dependent cell lines and inhibition of these responses
      by neutralizing monoclonal antibodies. Both CSA and FK506 inhibited mast cell
      cytokine production at concentrations comparable to those observed with T cells.
      However, the degree of inhibition of cytokine production varied among the mast
      cell lines as well as between different cytokines produced by a given mast cell
      line. For example, CSA completely inhibited interleukin-2 (IL-2), IL-3, IL-4 and
      granulocyte-macrophage colony stimulating factor secretion by all three lines,
      with the exception that IL-2/IL-4 production by MCIII was partially resistant to
      inhibition by CSA. Similarly, FK506 completely inhibited cytokine production by
      MC/9, partially inhibited cytokine production by MCIII and had differential
      effects on IL-3/granulocyte-macrophage colony-stimulating factor and IL-2/IL-4
      production by MCVI. Consistent with their ability to selectively inhibit cytokine
      gene transcription in T cells, neither CSA nor FK506 inhibited factor-dependent
      proliferation by these mast cell lines. In view of the putative role of cytokines
      in inflammation and late phase asthmatic reactions, these observations may be of
      particular significance in development of methods of pharmacologic intervention.

PMID- 1371159
TI  - Relief of experimental spasticity and anxiolytic/anticonvulsant actions of the
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate antagonist 2,3-dihydroxy-6
      nitro-7-sulfamoyl-benzo(F)quinoxaline.
AB  - Spasticity is characterized by pathological overactivity in spinal stretch reflex
      circuits and may be associated with disturbances in excitatory amino acid
      mediated transmission in the cord. A genetically determined syndrome of
      spasticity in the rat permits the quantitative evaluation of the antispastic
      effects of drugs by recording activity in the electromyogram (EMG) from a hind
      limb extensor muscle. In genetically spastic rats, systemic administration of the
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist, 2,3
      dihydroxy-6-nitro-7-sulfamoyl-benzo(F) quinoxaline (NBQX), normalized
      pathologically increased EMG activity, whereas the AMPA agonist, alpha-amino-3
      hydroxy-5-tertbutyl-4-isoxazolepropionate (ATPA), exacerbated the EMG measures of
      spasticity. The reflex mechanisms in the spinal cord can be studied in mice using
      EMG recordings from the tibial muscle (Hoffmann reflex) or from the plantar foot
      muscle (flexor reflex) after electrical stimulation of the tibial nerve. Systemic
      and i.t. administration of NBQX blocked Hoffmann reflexes in mice, leaving flexor
      reflexes unchanged. ATPA enhanced Hoffmann, and had no effect on flexor reflexes.
      The effects of NBQX on spinal reflexes were seen in doses which do not affect
      locomotor activity, but show anxiolytic and some antiepileptic activity in
      rodents. These data suggest that the design of novel muscle relaxant drugs acting
      at the AMPA subtype of glutamate receptors may be feasible.

PMID- 1371160
TI  - Botulinum C2 toxin and steroid production in adrenal Y-1 cells: the role of
      microfilaments in the toxin-induced increase in steroid release.
AB  - Exposure of adrenal Y-1 cells to C2 toxin results in an increase in steroid
      release that is accompanied by a rounding of the cell. The actions of C2 toxin
      mimic those of adrenocorticotropin and cholera toxin except that there is no
      increase in intracellular cyclic AMP content. In the present study we provide
      evidence that C2 toxin increases steroid output from Y-1 cells through an
      alteration in the microfilament network of the cell. C2 toxin significantly
      increased steroid output after 3 hr of exposure. This effect was accompanied by a
      significant increase in the transport of [3H]cholesterol to the mitochondrial
      fraction, independent of cholesterol uptake by the cell. The toxin was unable to
      increase steroid output from cells prerounded in suspension culture. The protease
      inhibitors benzamidine and phenylmethylsulfonyl fluoride did not attenuate the
      ability of C2 toxin to alter the morphology of Y-1 cells. A 3-hr exposure to C2
      toxin resulted in the ADP-ribosylation of 50 to 60% of the total actin pool.
      Fluorescein isothiocyanate-labeled phalloidin visualization of the cytoskeleton
      of toxin-treated cells confirmed that the toxin caused a decrease in the stress
      fiber network. C2 toxin treatment of a protein kinase A mutant Y-1 cell (Kin 8)
      resulted in morphological changes and an increase in steroid output that was not
      different from that observed for wild type Y-1 cells. The data suggest that C2
      toxin increases steroid output from adrenal Y-1 cells by a cyclic AMP-independent
      mechanism that involves the microfilament network of the cell.

PMID- 1371161
TI  - Tin-protoporphyrin: a potent inhibitor of hemoprotein-dependent steroidogenesis
      in rat adrenals and testes.
AB  - The present investigation provides evidence of the ability of Sn-protoporphyrin
      to cause striking alterations in adrenal and testicular cytochrome P-450
      dependent steroidogenesis and defines the potential of this metalloporphyrin to
      serve as a cellular toxin. Sn-protoporphyrin is currently used on an experimental
      basis for treatment of hyperbilirubinemias in humans, including newborn infants.
      Specifically, in the adrenals of rats treated with a moderate regimen of Sn
      protoporphyrin (two doses of 50 mumol/kg, s.c.), marked decreases of 60 to 70% in
      the microsomal 21 alpha-hydroxylase and the mitochondrial 11 beta-hydroxylase
      activities were observed after 7 days. Concomitant with these decreases was a
      significant depression in the adrenal mitochondrial cytochrome P-450 content and
      a notable reduction (approximately 30%) in serum corticosterone levels.
      Similarly, in the testes, significant decreases in the microsomal and
      mitochondrial cytochrome P-450 contents and the microsomal 17 alpha-hydroxylase
      activity were observed. Serum testosterone level, however, was not decreased,
      reflecting an absence of decrease in side chain cleavage activity.
      Metalloporphyrin caused a striking decrease of 65 to 80% in the microsomal heme
      oxygenase activity in the testes and the adrenals, as well as significant
      reductions in NADPH-cytochrome P-450 reductase activity of the organs. The
      decrease in heme oxygenase activity, however, as suggested by Western
      immunoblotting, apparently resulted, to a large extent, from the loss of enzyme
      protein integrity rather than a competitive inhibition of activity. At the
      transcript level, Northern blot analysis using a full length rat testis cDNA
      probe for heme oxygenase-2 mRNA indicated that Sn-protoporphyrin treatment did
      not decrease the amount of message for either of the heme oxygenase-2 transcripts
      (1.3 and 1.9 Kb).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371162
TI  - Cranial ontogeny in the direct-developing frog, Eleutherodactylus coqui (Anura:
      Leptodactylidae), analyzed using whole-mount immunohistochemistry.
AB  - Direct development in amphibians is an evolutionarily derived life-history mode
      that involves the loss of the free-living, aquatic larval stage. We examined
      embryos of the direct-developing anuran Eleutherodactylus coqui (Leptodactylidae)
      to evaluate how the biphasic pattern of cranial ontogeny of metamorphosing
      species has been modified in the evolution of direct development in this lineage.
      We employed whole-mount immunohistochemistry using a monoclonal antibody against
      the extracellular matrix component Type II collagen, which allows visualization
      of the morphology of cartilages earlier and more effectively than traditional
      histological procedures; these latter procedures were also used where
      appropriate. This represents the first time that initial chondrogenic stages of
      cranial development of any vertebrate have been depicted in whole-mounts. Many
      cranial cartilages typical of larval anurans, e.g., suprarostrals, cornua
      trabeculae, never form in Eleutherodactylus coqui. Consequently, many regions of
      the skull assume an adult, or postmetamorphic, morphology from the inception of
      their development. Other components, e.g., the lower jaw, jaw suspensorium, and
      the hyobranchial skeleton, initially assume a mid-metamorphic configuration,
      which is subsequently remodeled before hatching. Thirteen of the adult complement
      of 17 bones form in the embryo, beginning with two bones of the jaw and jaw
      suspensorium, the angulosplenial and squamosal. Precocious ossification of these
      and other jaw elements is an evolutionarily derived feature not found in
      metamorphosing anurans, but shared with some direct-developing caecilians. Thus,
      in Eleutherodactylus cranial development involves both recapitulation and
      repatterning of the ancestral metamorphic ontogeny.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1371163
TI  - Necrosis and inhibition of growth of human lung tumor by anti-alpha-human
      chorionic gonadotropin antibody.
AB  - Human lung tumor cells (ChaGo) established in culture from a bronchogenic
      squamous cell carcinoma synthesize and secrete large amounts of human chorionic
      gonadotropin (HCG), predominantly the alpha subunit of the glycoprotein hormone.
      ChaGo cells lose their transformation phenotypes following treatment with anti
      alpha-HCG antibody or following inhibition of intracellular synthesis of alpha
      HCG by the anti-sense RNA technique. We report that tumors induced by ChaGo cells
      in female athymic mice undergo necrotic degeneration following local or
      intraperitoneal administration of alpha-HCG-specific-antibody. The alpha-HCG
      antibody did not affect the growth of tumor induced by alpha-HCG nonproducing
      human tumor cells. Histopathological examinations of the anti-alpha-HCG antibody
      treated tumor tissues showed active necrosis. When the antibody treatment was
      discontinued, the tumorigenesis process resumed. When anti-alpha-HCG antibody was
      administered simultaneously with ChaGo cells, a concentration-dependent
      inhibition of tumor growth in athymic mice was completely prevented at higher
      concentrations of the specific antibody.

PMID- 1371165
TI  - Ty3 GAG3 and POL3 genes encode the components of intracellular particles.
AB  - Ty3 is a Saccharomyces cerevisiae retrotransposon that integrates near the
      transcription initiation sites of polymerase III-transcribed genes. It is
      distinct from the copialike Ty1 and Ty2 retrotransposons of S. cerevisiae in both
      the sequences of encoded proteins and gene order. It is a member of the gypsylike
      family of retrotransposons which resemble animal retroviruses. This study was
      undertaken to investigate the nucleocapsid particle of a transpositionally active
      gypsylike retrotransposon. Characterization of extracts from cells in which Ty3
      expression was induced showed the presence of Ty3 nucleoprotein complexes, or
      viruslike particles, that migrated on linear sucrose gradients with a size of
      156S. These particles are composed of Ty3 RNA, full-length, linear DNA, and
      proteins. In this study, antibodies raised against peptides predicted from the
      Ty3 sequence were used to identify Ty3-encoded proteins. These include the capsid
      (26 kDa), nucleocapsid (9 kDa), and reverse transcriptase (55 kDa) proteins. Ty3
      integrase proteins of 61 and 58 kDa were identified previously (L. J. Hansen and
      S. B. Sandmeyer, J. Virol. 64:2599-2607, 1990). Reverse transcriptase activity
      associated with the particles was measured by using exogenous and endogenous
      primer-templates. Immunofluorescence studies of cells overexpressing Ty3 revealed
      cytoplasmic clusters of immunoreactive proteins. Transmission electron microscopy
      showed that Ty3 viruslike particles are about 50 nm in diameter. Thus, despite
      the unusual position specificity of Ty3 upstream of tRNA-coding regions, aspects
      of the Ty3 life cycle are fundamentally similar to those of retroviruses.

PMID- 1371164
TI  - The dominant linear neutralizing antibody-binding site of glycoprotein gp86 of
      human cytomegalovirus is strain specific.
AB  - Bacterial fusion proteins, constructed from overlapping fragments of the open
      reading frame coding for gp86 of human cytomegalovirus (HCMV) strain AD169, were
      used to localize antigenic regions recognized by antibodies from human
      convalescent sera. A major domain for binding of conformation-independent
      antibodies was localized on fusion protein AP86, containing amino acids 15 to 142
      of gp86. Human antibodies, affinity purified on AP86, neutralized infectious
      virus in tissue culture. In addition, a mouse monoclonal antibody (AP86-SA4),
      raised against AP86, also neutralized HCMV. AP86-SA4 was reactive with viral gp86
      in immunoblot assays and showed a plasma membrane staining on intact HCMV
      infected fibroblasts late in infection. After exonuclease III deletions of the
      viral gene, the binding site of neutralizing human as well as mouse antibodies
      was localized between amino acid residues 34 and 43. The domain has sequence
      variation between laboratory strains AD169 and Towne, and binding of the
      antibodies was strain specific. To our knowledge, this is the first
      characterization of a strain-specific neutralizing epitope on HCMV.

PMID- 1371166
TI  - Characterization of the interaction of polyomavirus middle T antigen with type 2A
      protein phosphatase.
AB  - Two cellular proteins of 36 and 63 kDa which bind the small T and middle T
      antigens of polyomavirus recently have been identified as the catalytic and
      regulatory subunits of the phosphoserine/threonine-specific type 2A protein
      phosphatase (PP2A). We report here the presence of phosphoseryl phosphatase
      activity associated with polyomavirus small T and middle T antigens in
      immunoprecipitates prepared from virus-infected and transformed cells.
      Phosphatase activity was also found associated with middle T-antigen mutants,
      some of which had been defined previously to associate with 36- and 63-kDa
      cellular proteins. Middle T-antigen-associated phosphatase activity was sensitive
      to okadaic acid and microcystin-LR, inhibitors of PP2A, and insensitive to
      inhibitor 1 or 2, orthovanadate, or EDTA. Using antiserum specific for the
      catalytic subunit of PP2A, we found that unlike the majority of PP2A, middle T
      antigen-bound PP2A was membrane associated. However, no gross change in the
      amount, activity, or localization of PP2A could be attributed to middle T-antigen
      expression in transformed cells. Anti-PP2A antibodies coprecipitated a 63-kDa
      protein from normal cells and in addition coprecipitated middle T antigen, 60-
      and 61-kDa proteins (identified as src family members), and an 81-kDa protein
      from middle T-antigen-transformed cells. Furthermore, we detected protein kinase
      activity in PP2A immunoprecipitates and protein phosphatase activity in src
      immune complexes from extracts of middle T-antigen-transformed, but not normal,
      cells. These results reinforce the notion that at least a portion of middle T
      antigen bridges a protein kinase with a protein phosphatase.

PMID- 1371167
TI  - High-frequency intracellular transposition of a defective mammalian provirus
      detected by an in situ colorimetric assay.
AB  - We devised an indicator gene for retrotransposition, nlsLacZRT, which contains
      the Escherichia coli lacZ gene fused to a nuclear location signal (nlsLacZ),
      engineered in such a way that the gene is expressed only if the structure in
      which it has been inserted transposes itself through an RNA intermediate. A
      cloned murine leukemia retrovirus with an ecotropic host range (Moloney murine
      leukemia virus), rendered defective by a large deletion encompassing the three
      viral gag, pol, and env open reading frames, was marked with this indicator gene
      and introduced by transfection into heterologous feline cells. No beta
      galactosidase activity could be detected among the clonal cell population, unless
      the defective provirus was complemented in trans by the gag-pol gene products.
      Under these conditions, cell variants which disclosed an easily detectable
      nuclear blue coloration upon in situ 5-bromo-4-chloro-3-indolyl-beta-D
      galactopyranoside staining were observed. Fluorescence-activated cell sorting of
      the beta-galactosidase-positive cells, followed by Southern blot analysis,
      demonstrated an unambiguous correlation between nlsLacZRT activation and
      retrotransposition of the marked provirus. Transposition occurs at a high
      frequency (up to 10(-4) events per cell per generation), which is dependent on
      the level of expression of the gag-pol gene and is concomitant with the release
      of noninfectious retroviruslike particles which are the hallmarks, but not the
      intermediates, of the intracellular transposition process.

PMID- 1371168
TI  - The baculovirus-integrated retrotransposon TED encodes gag and pol proteins that
      assemble into viruslike particles with reverse transcriptase.
AB  - TED is a lepidopteran retrotransposon found inserted within the DNA genome of the
      Autographa californica nuclear polyhedrosis virus mutant, FP-D. To examine the
      proteins and functions encoded by this representative of the gypsy family of
      retrotransposons, the gag- and pol-like open reading frames (ORFs 1 and 2) were
      expressed in homologous lepidopteran cells by using recombinant baculovirus
      vectors. Expression of ORF 1 resulted in synthesis of an abundant TED-specific
      protein (Pr55gag) that assembled into viruslike particles with a diameter of 55
      to 60 nm. Expression of ORF 2, requiring a -1 translational frameshift, resulted
      in synthesis of a protease that mediated cleavage of Pr55gag to generate p37, the
      major protein component of the resulting particles. Expression of ORF 2 also
      produced reverse transcriptase that associated with these particles. Both
      protease and reverse transcriptase activities mapped to domains within ORF 2 that
      contain sequence similarities with the corresponding functional domains of the
      pol gene of the vertebrate retroviruses. These results indicated that TED ORFs 1
      and 2 functionally resemble the retrovirus gag and pol genes and demonstrated for
      the first time that an invertebrate member of the gypsy family of elements
      encodes active forms of the structural and enzymatic functions necessary for
      transposition via an RNA intermediate. TED integration within the baculovirus
      genome thus represents one of the first examples of transposon-mediated transfer
      of host-derived genes to an eukaryotic virus.

PMID- 1371169
TI  - Analysis of T- and B-cell epitopes of capsid protein of rubella virus by using
      synthetic peptides.
AB  - A nested set of 11 overlapping synthetic peptides covering the entire sequence of
      rubella virus capsid protein was synthesized, purified, and tested against human
      rubella virus-specific T-cell lines and rubella virus-seropositive sera. T-cell
      lines derived from four donors responded strongly to four synthetic peptides
      containing residues 96 to 123, 119 to 152, 205 to 233, and 255 to 280. Only one
      peptide (residues 255 to 280) was recognized by all four T-cell lines. Two human
      immunodominant linear B-cell epitopes were mapped to residues 1 to 30 and 96 to
      123 by using peptide-specific enzyme-linked immunosorbent assay. All 11 synthetic
      peptides were highly immunogenic and induced strong antibody responses in rabbits
      against the respective immunized peptides. Seven of the 11 rabbit antipeptide
      antisera (anti-1-30, -74-100, -96-123, -119-152, -205-233, -231-257, and -255
      280) specifically recognized the capsid protein on immunoblots. Identification of
      these T- and B-cell epitopes represents the first step toward rational design of
      synthetic vaccines against rubella.

PMID- 1371170
TI  - A nuclear single-stranded-DNA binding factor interacts with the long terminal
      repeats of the 1731 Drosophila retrotransposon.
AB  - Using gel mobility assays, we have detected two proteins that bind in the U3
      region of the 1731 retrotransposon long terminal repeats (between positions -110
      and -73) in nuclear extracts from Drosophila melanogaster cultured cells. The
      first one binds double-stranded DNA, whereas the other binds the mRNA-like strand
      in a sequence-specific manner. We report here the characterization of the latter
      protein, named NssBF for nuclear single-stranded-DNA binding factor. Gel
      filtration shows an apparent molecular mass of 95 kDa for NssBF. The points of
      contact between NssBF and its single-stranded DNA target were determined. This
      protein binds neither the complementary strand nor the corresponding RNA
      sequence. A possible role of NssBF in transcription is discussed.

PMID- 1371171
TI  - Transformation-defective mutants of polyomavirus middle T antigen associate with
      phosphatidylinositol 3-kinase (PI 3-kinase) but are unable to maintain wild-type
      levels of PI 3-kinase products in intact cells.
AB  - Middle T antigen (MT) of polyomavirus causes transformation by associating with a
      number of cellular proteins. The association with and activation of two such
      proteins, phosphatidylinositol 3-kinase (PI 3-kinase) and pp60c-src, appears to
      be necessary for transformation by MT. The tyrosine kinase activity of MT
      associated pp60c-src is significantly increased when assayed in vitro, and levels
      of phosphotyrosine-containing proteins are elevated in vivo. Similarly, levels of
      the PI 3-kinase products phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and
      phosphatiylinositol-3,4,5-trisphosphate [PI(3,4,5)P3] are constitutively elevated
      in MT-transformed cells. However, the formation of a complete MT/cellular protein
      complex and the activation of tyrosine kinase are not sufficient to cause
      transformation, since the transformation-defective mutants 248m and dl1015
      associate with all wild-type MT-associated proteins, including PI 3-kinase and
      pp60c-src, and neither mutant appears to be defective in MT-associated tyrosine
      kinase activity. Studies presented here compared (i) the amount of PI 3-kinase
      activity associated with the MT complex and (ii) levels of [3H]inositol
      incorporation into PI 3-kinase products in cells expressing mutant or wild-type
      MT. The results show that dl1015 is defective in both assays, whereas 248m is
      defective only for incorporation of [3H]inositol into PI(3,4,5)P2 and PI(3,4)P3.
      These findings identify a biochemical defect in the 248m mutant and corroborate
      previous results correlating transformation and elevated levels of PI 3-kinase
      products in vivo. In addition, they indicate that PI 3-kinase product levels are
      affected by factors other than simply the amount of PI 3-kinase activity
      associated with the MT complex.

PMID- 1371172
TI  - Resistance to influenza virus infection of Mx transgenic mice expressing Mx
      protein under the control of two constitutive promoters.
AB  - Transgenic mice constitutively expressing in the brain the influenza virus
      resistance protein Mx1 controlled by the HMG (3-hydroxy-3-methylglutaryl coenzyme
      A reductase) promoter showed specific resistance against the neurotropic
      influenza A virus strain NWS. Control mice of the A2G strain express Mx1 protein
      in all organs, but only after induction by interferon type I upon or without
      viral infection. The extent of specific resistance in transgenic mice of the best
      expressing line reached about two-thirds that of controls, most likely because of
      considerably less total-body Mx protein activity in the transgenic mice. Thus,
      the theoretical advantage in these mice of the continuous presence of Mx protein
      with early inhibitory potential to viral replication was apparently offset by
      restricted organ expression. Strong evidence that the Mx1 protein on its own is a
      specific anti-influenza A virus agent and that its efficiency in the experimental
      setting is independent of interferon actions could be derived from the treatment
      of experimental and control mice with anti-interferon antibodies at the time of
      virus tests. Whereas in A2G mice, Mx1 mRNA and Mx1 protein synthesis were
      abolished and viral resistance was markedly reduced or abolished, resistance in
      the transgenic mice persisted to almost the same degree. Transgenic mice
      generated with a mouse albumin/Mx1 cDNA construct showed liver-specific
      expression. However, in two expressing transgenic lines, Mx1 protein synthesis
      was suppressed after a few months. The mechanism of suppression could not be
      elucidated, but increasing methylation of the transgene's coding region was not
      the cause. It is possible that continuous Mx1 protein expression in the liver is
      less well tolerated than that in the brain. Whether this partial suppression and,
      with the HMG promoter, restricted organ expression are the organism's responses
      to interference of Mx1 with normal cellular activities such as nucleocytoplasmic
      transport of RNA and proteins cannot be determined until the molecular mechanisms
      of antiviral activity of Mx1 protein are understood.

PMID- 1371175
TI  - Estrogen receptor in carcinoma in situ of the cervix.
AB  - The lining epithelium of the human cervix uteri is an estrogen dependent tissue
      containing specific intracellular receptors for this hormone. However, the
      influence of estrogen on an early neoplastic lesion arising from this epithelium,
      such as carcinoma in situ of the cervix, has not been determined. We evaluated 24
      formalin fixed paraffin embedded tissue specimens of cervical carcinoma in situ
      for the presence of estrogen receptor by the immunoperoxidase technique. The
      antigenic sites of estrogen receptor were exposed by DNAse treatment followed by
      peroxidase-antiperoxidase (PAP) staining with monoclonal antibody against
      estrogen receptor. Parallel negative controls were run using negative control
      antibody and rat serum. Quality control for positive staining was performed using
      breast cancer tissue sections from specimens with known estrogen receptor
      detected by the radioreceptor method. Strongly positive staining was observed in
      all specimens in the nuclei of glandular epithelium, stromal cells, and basal and
      parabasal cells. However, nuclei within carcinoma in situ of the cervix showed no
      evidence of positive staining. Due to lack of specific intracellular receptor for
      estrogen, it appears that carcinoma in situ of the cervix will not be under
      direct influence of estrogen.

PMID- 1371173
TI  - Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in
      quiescent cells can function as intermediates in the retroviral life cycle.
AB  - Using a quantitative polymerase chain reaction (PCR) method, we have previously
      shown that a molecularly cloned isolate of human immunodeficiency virus type 1
      (HIV-1) can efficiently enter quiescent primary lymphocytes; however, the reverse
      transcription process is not completed in these cells. In this study, we further
      characterized the reverse transcription of HIV-1 in quiescent cells, and our
      results indicate that while initiation of reverse transcription occurs
      simultaneously in both activated and quiescent lymphocytes, it not only ends
      prematurely but also proceeds more slowly in quiescent cells. We also performed
      experiments to address the role of partial reverse transcripts as intermediates
      in the viral life cycle. We used azidothymidine either before or after infection
      with HIV-1 to prevent formation of and further DNA synthesis by partial reverse
      transcripts, respectively. Decreases in virus production from these cells
      following mitogenic stimulation indicated that partial reverse transcripts can
      contribute significantly to virus rescue from infected quiescent cells stimulated
      subsequent to infection. Furthermore, we established that mitogenic stimulation
      of infected quiescent cells induces reinitiation of DNA synthesis from partial
      reverse transcripts. However, the virus rescue is inefficient relative to the
      initial multiplicity of infection, and this is explained by inefficient
      completion of DNA synthesis from the partial reverse transcript. Thus, the arrest
      of reverse transcription in quiescent cells may play an important role in HIV-1
      pathogenesis by contributing to the inefficient infection of potential target
      cells in the peripheral blood of HIV-1-infected individuals.

PMID- 1371174
TI  - Cloning of noncultivatable human rotavirus by single primer amplification.
AB  - A novel, sequence-independent strategy has been developed for the amplification
      of full-length cDNA copies of the genes of double-stranded RNA (dsRNA) viruses.
      Using human (Bristol) group C rotavirus as an example, a single amino-linked
      modified oligonucleotide (primer 1) was ligated to either end of each dsRNA
      genome segment by using T4 RNA ligase. Following reverse transcription,
      annealing, and repair of cDNA strands, amplification of the viral dsRNA genome
      was accomplished by polymerase chain reaction using a single complementary
      oligonucleotide (primer 2). Northern (RNA) hybridization of cDNA to virus dsRNA
      indicated that it was possible to generate cDNA representing the complete genome
      from very small clinical samples. This technique was used to determine the
      complete nucleotide sequence (728 bp) and coding assignment of gene 10, which
      revealed an open reading frame of 212 amino acids with limited homology to NS26
      from human group A rotavirus. In contrast to previous tailing methods, the
      addition of one defined primer allowed unequivocal identification of terminal
      nucleotides and should be generally applicable to viruses with segmented dsRNA
      genomes and especially for analysis of clinical samples, for which very limited
      quantities of biological material are available.

PMID- 1371176
TI  - Distribution of 111In-bleomycin complex in small cell lung cancer cells by
      autoradiography.
AB  - The distribution of 111In-bleomycin Complex (111In-BLMC) in small cell lung
      cancer (SCLC) cells was studied by autoradiography. SCLC cells were exposed to
      111In-BLMC and 111Indium chloride (111InCl3) for 1 hour, 3 hours, and 4 hours;
      washed with fresh medium; and spread on slides. The slides were smeared with NTB2
      (NTB3) emulsion by wet or dry-mount technique and exposed 3 to 15 days. 111In
      BLMC was found to localize in the cell nucleus and nuclear membrane (78.3%);
      111InCl3 located mainly in the cytoplasm (52.3%). This distribution of labeled
      BLM may explain the mechanism of killing SCLC cells by 111In-BLMC.

PMID- 1371177
TI  - Inhibition of HIV-1 reverse transcriptase and virus replication by a non
      nucleoside dipyridodiazepinone BI-RG-587 (Nevirapine).

PMID- 1371179
TI  - Endorphin-like immunoreactivities in uncultured and cultured human peripheral
      blood mononuclear cells.
AB  - It has been reported that cells of the immune system produce and release
      considerable amounts of pro-opiomelanocortin (POMC) -derived peptides in response
      to coculture with a variety of stimulatory agents. The present study investigated
      whether extracts of human peripheral blood mononuclear cells (PBMC) contain
      immunoreactivity for beta-endorphin (beta E) and related peptides. Using four
      endorphin RIA systems with different specificities, extracts of freshly isolated
      PBMC and PBMC cultured in the presence or absence of mitogens or of corticotropin
      releasing factor (CRF) and vasopressin (VP), were analyzed. With a
      radioimmunoassay (RIA) system directed to the midportion of beta E,
      immunoreactivity (MP beta E-IR) was readily detectable, although the
      concentration was extremely low (ca. 200 pg/10(7) cells). beta E immunoreactivity
      (beta E-IR) and alpha-endorphin immunoreactivity (alpha E-IR), as determined in C
      terminally directed RIA systems, were present in even lower concentrations. gamma
      Endorphin immunoreactivity (gamma E-IR) was hardly detectable. Of subsets
      enriched in T-cells, B-cells or monocytes, the highest concentration of MP beta E
      IR was detected in extracts of monocytes. Coculture of PBMC with the mitogen
      Concanavalin A (Con A) or Phytohaemagglutinin (PHA) increased the amount of MP
      beta E-IR in extracts of the cells. No increase in alpha E-IR, however, was
      detected, whereas beta E-IR was only increased in extracts of cells cultured in
      the presence of Con A. No increase, in any of the immunoreactivities, was
      observed in extracts of PBMC cultured with bacterial lipopolysaccharide (LPS) or
      with the combination of CRF and VP, both stimuli that have been reported to
      induce POMC peptides in cultured PBMC. The present data show that human PBMC
      contain endorphin-like immunoreactivity, but in very small amounts. The extremely
      low concentrations and the ineffectiveness of LPS and the combination of CRF and
      VP to increase the endorphin-like immunoreactivity raise questions about the
      reported capacity of PBMC to synthesize POMC-derived peptides.

PMID- 1371178
TI  - Hyaluronan synthesis in the adult guinea pig endolymphatic sac.
AB  - The endolymphatic sac is believed to play a major role in membranous labyrinth
      homeostasis by controlling the volume of endolymph, removing debris, and
      participating in the immune response of the inner ear. The endolymphatic sac is
      postulated to absorb endolymph and to synthesize and secrete high-molecular
      weight and osmotically active glycosaminoglycans (GAGs). The present study
      examines the ability of in vitro adult guinea pig endolymphatic sac cells to
      synthesize complex proteins and polysaccharides. The intent is to characterize
      the nature of these compounds by studying carbon-14 (14C) glucose incorporation
      in tissue cultured endolymphatic sac specimens using autoradiographic and
      specific enzymatic digestion techniques. Our results suggest that sac cells can
      synthesize GAGs and proteins in vitro in proportionately larger amounts than
      surrounding connective tissue and dura. The principal GAG synthesized by the
      endolymphatic sac appears to be hyaluronan.

PMID- 1371180
TI  - Effects of the S2-serotonergic receptor antagonist, ketanserin, on cerulein
      induced pancreatitis in the rat.
AB  - We investigated the effects of ketanserin, a S 2 (5-hydroxytryptamine 2; 5-HT 2)
      serotonergic receptor antagonist, on cerulein-induced pancreatitis in the rat.
      Large pharmacological doses of cerulein induced acute pancreatitis in the rat.
      Ketanserin reduced the cerulein-induced increase in serum amylase concentration
      in a dose-dependent manner. Treatment with 10 mg/kg of ketanserin per os markedly
      improved cerulein-induced pancreatitis and was associated with a significant
      reduction of the increase in serum amylase concentration. In addition, a very
      specific serotonin S 2 antagonist, ritanserin which has no antihypertensive
      effect, also reduced the cerulein-induced increase in the serum amylase
      concentration. These results suggest that S 2 (5-HT 2) may play a role in
      pathophysiology of cerulein-induced pancreatitis in the rat.

PMID- 1371181
TI  - The copy number of plasmid pLS1 is regulated by two trans-acting plasmid
      products: the antisense RNA II and the repressor protein, RepA.
AB  - The promiscuous plasmid pLS1 encodes two transacting elements that regulate its
      copy number: protein RepA and antisense RNA II. In vitro transcription showed
      that RNAs for both repressors are synthesized from two promoters, PAB and PII.
      From PAB, genes encoding RepA (transcriptional repressor) and RepB (initiator of
      replication) are cotranscribed, the target of RepA being located within PAB.
      Mutants in repA or in PAB are still sensitive to RepA. However, cloning of the
      repA gene in a compatible replicon did not result in incompatibility towards
      pLS1. From PII, the 50-nucleotide RNA II is synthesized. The main incompatibility
      determinant towards pLS1 corresponds to the coding sequence for RNA II. The RNA
      II target could be reduced to 21 nucleotides, including the RepB initiation of
      translation signals. We propose that plasmids of the pLS1 family (pE194, pADB201,
      and pLB4) share functional and structural characteristics for the regulation of
      their copy numbers.

PMID- 1371182
TI  - Hydrolysis of substance P in the rabbit retina: I. Involvement of acetylcholine
      and acetylcholinesterase. An in vivo study.
AB  - The laminar patterns of acetylcholinesterase (AChE) activity and substance P (SP)
      immunoreactivity within the inner plexiform layer (IPL) of the rabbit retina show
      striking similarities. Discrete bands of SP-immunoreactivity were seen at 1-7%,
      40-48% and 85-95% depth of IPL. AChE activity was present throughout the entire
      thickness of the IPL with moderately stained bands in each sublamina (3-24% in
      sublamina a and 62-89% in sublamina b depth IPL). These bands were bordered on
      both sides by bands of even greater density (in sublamina a 0-3% and 24-34% and
      in sublamina b 55-62% and 89-100% depth IPL). Cell processes staining for choline
      acetyltransferase (ChAT) have previously been shown to ramify at 19-24% and 63
      79% depth levels. Thus, SP- and ChAT-immunoreactive bands are located in both
      sublaminae, positioned within regions of moderate AChE activity and flanked by
      bands with greater AChE activity. This strong morphological correspondence and
      reported interactions between acetylcholine (ACh), AChE and SP in vitro provide
      the basis for the present study to determine whether such interactions can be
      demonstrated in vivo. Retinas infused with ACh showed a 60% average increase in
      SP-IR as compared with untreated retinas from the same animals. Treatment with
      diisopropylfluorophosphate (DFP) also resulted in a 56% increase in SP-IR. The
      ability of ACh to induce increased levels of SP was not inhibited by CoCl2,
      atropine or mecamylamine, ruling out the possibilities of polysynaptic
      transmission or involvement of muscarinic or nicotinic receptors. Infusion of ACh
      did not increase the levels of preprotachykinin-mRNA indicating that the increase
      in SP-IR is not due to de novo synthesis but rather to inhibition of the
      enzyme(s) responsible for SP degradation. Whether AChE functions alone or in
      concert with other enzymes to hydrolyze SP cannot be determined from these
      experiments but is addressed in a separate study.

PMID- 1371183
TI  - Hydrolysis of substance P in the rabbit retina: II. The role of a membrane
      associated acetylcholine-sensitive metalloendopeptidase. An in vitro study.
AB  - Studies in the rabbit retina have shown that infusion of exogenous acetylcholine
      (ACh) into the vitreal chamber leads to an increase in the amount of substance P
      (SP) immunoreactivity (Goebel and Pourcho, submitted). This increase was
      determined to be independent of new peptide synthesis, suggesting that the
      elevated level of SP is the result of ACh inhibition of an SP-degrading protease.
      This phenomenon has now been confirmed in vitro in both tissue slice and retinal
      homogenate assays. These studies have shown that ACh decreases the rate of SP
      hydrolysis in a concentration dependent manner. Recovery of SP hydrolytic
      activity following ACh inhibition was found to be directly proportional to the
      amount of acetylcholinesterase (AChE) activity in the membrane fraction. Specific
      protease inhibitors were used to determine the relative contributions of membrane
      associated retinal enzymes to SP-hydrolysis. In the presence of 1 mM 1,10
      phenanthroline or p-chloromercuribenzenesulfonic acid all SP-hydrolytic activity
      was abolished, indicating that the enzyme(s) responsible for the degradation of
      the peptide is a metallopeptidase. The ACh sensitive retinal enzyme was found to
      be concentrated in the membrane fraction where it accounts for approximately 70%
      of the SP hydrolytic activity. Although the precise identity of this enzyme
      remains to be determined, the present evidence indicates that it shares many of
      the characteristics of the enzyme substance P-degrading endopeptidase (Endo et
      al. 1988, 1989). Enkephalinase activity was also found, contributing to 28% of
      the hydrolytic activity in the membrane fraction. However, the activity of this
      enzyme was insensitive to elevated levels of ACh. After initial cleavage of SP by
      the primary hydrolytic enzymes, further degradation of the fragments appears to
      be carried out by membrane associated serine protease(s). The activity exhibited
      by this class of enzymes was inhibited by DFP treatment and was not sensitive to
      ACh. Although AChE does not make a major contribution to the hydrolysis of SP, it
      does participate in peptide degradation via its esterase activity which controls
      the level of ACh, thereby modulating the primary SP-hydrolytic enzyme.

PMID- 1371184
TI  - Microvascular decompression and partial sensory rhizotomy in the treatment of
      trigeminal neuralgia: personal experience with 220 patients.
AB  - The results of the treatment of trigeminal neuralgia by neurovascular
      decompression or partial sensory rhizotomy in a personal series of 220 patients
      are presented. Microvascular decompression was performed in 178 patients and
      partial sensory rhizotomy in 42. The mean follow-up was 5.2 years. Immediate pain
      relief was achieved in 94% of all patients, but the rate dropped to 84% during
      the follow-up period. The recurrence rate in the microvascular decompression
      group was 6% and in the PSR 49%. Permanent sequelae occurred in 4 patients (loss
      of hearing, 1; loss of corneal reflex, 1; lesion of the portio minor, 2), but
      transitory complications (impaired hearing caused by hematotympanum and diplopia)
      were more frequent, especially in the beginning of the series. Elderly patients
      tolerated the procedure very well and the percentage of complications was evenly
      distributed in all age groups. Three patients died. No patient developed painful
      dysesthesias or anesthesia dolorosa. There were no differences in the outcome,
      considering sex and age. The duration of symptoms did not influence the
      prognosis. Patients with severe compression did better than those with a mild
      one, and patients with an arterial compression did better than those with a
      venous one. Trigeminal neuralgia in multiple sclerosis is seldom relieved by
      microvascular decompression. The experience of the surgeon reduces the number of
      negative findings considerably.

PMID- 1371185
TI  - A flow cytometric study of 137 fresh hydropic placentas: correlation between
      types of hydatidiform moles and nuclear DNA ploidy.
AB  - Hydropic placentas may be classified by histopathology into hydropic abortus,
      partial hydatidiform mole, and complete hydatidiform mole. We studied 142
      hydropic placentas: 39% were complete hydatidiform moles, 35% partial
      hydatidiform moles, and 26% hydropic abortuses. Villous vesicle size was
      predictive of histologic diagnosis. We determined DNA ploidy in 137 cases.
      Seventy-three percent of hydropic abortuses were diploid and 11% were triploid.
      Ninety percent of partial moles were triploid or near-triploid; one partial mole
      was haploid and one diploid. Of the complete moles, 50% were diploid, 43% were
      tetraploid, 3.6% polyploid, and 1.7% triploid. Partial moles had lower pre
      evacuation beta-hCG levels than complete moles. Persistent tumor followed 33% of
      complete moles and 12% of partial moles. Although the numbers were small, no
      patient with a diploid, tetraploid, aneuploid, or haploid partial mole developed
      persistent disease. Among complete moles, the pre-evacuation beta-hCG level was
      not predictive of persistence (P = .15). Subdividing complete moles by ploidy, we
      found that tetraploid moles were associated with higher pre-evacuation beta-hCG
      levels than were diploid moles. However, tetraploidy was not associated with
      increased persistent tumor among complete moles. Although most partial moles were
      triploid and most complete moles were diploid or tetraploid, there was wider DNA
      heterogeneity among molar gestations than previously reported. In this series,
      DNA ploidy was not an independent predictor of persistence in complete moles.

PMID- 1371186
TI  - Identification of the 10Sa RNA structural gene of Mycobacterium tuberculosis.

PMID- 1371187
TI  - A rapid method for measuring the steady state levels of mitochondrial RNA in
      whole mitochondria.

PMID- 1371188
TI  - Visiting rules!

PMID- 1371189
TI  - Left behind.

PMID- 1371191
TI  - Should we lift or should we roll? Nursing practice following prosthetic hip
      surgery.
AB  - Following prosthetic hip surgery, patients are at high risk of pressure sores,
      and must be moved regularly. Although no research has concluded that dislocation
      is caused by moving patients in bed, lifting is still widely used. A flexible
      practice adapting to individual needs represents the best approach.

PMID- 1371190
TI  - Lipocortin and vasocortin: two species of anti-inflammatory proteins mimicking
      the effects of glucocorticoids.
AB  - The anti-inflammatory effect of glucocorticoids depends, at least in part, on the
      induction of two regulatory proteins, lipocortin and vasocortin, both preventing
      the release of inflammatory mediators. Lipocortin inhibits phospholipase A2
      (PLA2) and therefore reduces arachidonic acid metabolites formation. Vasocortin
      inhibits histamine release from mast cells. Lipocortin and vasocortin may be
      regarded as the first two identified members of the (perhaps greater) family of
      glucocorticoid-induced proteins.

PMID- 1371192
TI  - Fc gamma R-dependent regulation of the biosynthesis of complement C3 by murine
      macrophages: the modulatory effect of IL-6.
AB  - The effect of murine IgG isotypes on the gene expression and secretion of the
      third component of complement (C3) has been studied using the monocytoid cell
      line P388D1 and oil-elicited mouse peritoneal macrophages. It is demonstrated
      that the binding of IgG2a and IgG2b but not IgG1 and IgG3 augments the
      biosynthesis of C3 both in the presence and in the absence of the phorbol ester,
      phorbol myristate acetate in the case of both cell types. The multifunctional
      cytokine interleukin-6 (IL-6) alone reveals no effect on the gene expression of
      C3, but increases the effectiveness of mouse IgG2a and IgG2b. Confirming the role
      of Fc gamma RII, a strong up-regulation of C3 gene expression and C3 secretion
      was found when macrophages were cultured with the F(ab')2 fragment of the Fc
      gamma RII-specific monoclonal antibody 2.4G2.

PMID- 1371193
TI  - Insulin secretion from pancreatic B cells caused by L-arginine-derived nitrogen
      oxides.
AB  - L-arginine causes insulin release from pancreatic B cells. Data from three model
      systems support the hypothesis that L-arginine-derived nitrogen oxides (NOs)
      mediate insulin release stimulated by L-arginine in the presence of D-glucose and
      by the hypoglycemic drug tolbutamide. The formation of NO in pancreatic B cells
      was detected both chemically and by the NO-induced accumulation of guanosine
      3',5'-monophosphate. NG-substituted L-arginine analogs inhibited the release of
      both insulin and NO. Protein immunoblot and histochemical analysis with antiserum
      to type I NO synthase suggest that the formation of NO in pancreatic B cells is
      catalyzed by an NADPH- (reduced form of nicotinamide adenine dinucleotide
      phosphate), Ca2+/calmodulin-dependent type I NO synthase of about 150
      kilodaltons.

PMID- 1371194
TI  - Renal allograft-infiltrating lymphocytes. A prospective analysis of in vitro
      growth characteristics and clinical relevance.
AB  - One-hundred consecutive human renal allograft Tru-cut needle biopsies were
      studied for in vitro proliferation of T lymphocytes under restrictive culture
      conditions containing low-dose recombinant interleukin 2. Each biopsy was entered
      into a blinded code and evaluated prospectively for visual evidence of growth at
      24 hr and for sustained growth. Those T cell populations exhibiting sustained
      growth were then evaluated for cell surface phenotype by FACS; for allospecific
      cytotoxicity by 51Cr release; for a proliferative response to alloantigen by
      incorporation of [3H]-thymidine; and for secretion of IL-2, IL-4, IFN-gamma, and
      TNF-alpha in response to alloantigenic stimulation by ELISA. All results were
      compared with clinical diagnosis, immunosuppression at time of biopsy, diagnosis
      and phenotype by immunopathology, short-term outcome and long-term graft
      survival. Growth at 24 hr was predictive of acute cellular rejection (P less than
      0.0005), unrelated to chronic rejection (P = 0.663) or maintenance
      immunosuppression (P = 0.911), and inversely correlated with cyclosporine
      toxicity (P = 0.051) and treatment with OKT3 (P = 0.014). The CD4/CD8 ratio of
      the sustained T cell populations was unrelated to that seen on histological
      examination (correlation coefficient = -0.098 and 0.044 for diffuse and aggregate
      infiltrates, respectively). Cytotoxic specificity for HLA class II was mediated
      by CD4+ cells and for HLA class I by CD8+ cells. Enhanced secretion of IL-2 in
      response to alloantigen distinguished those cells associated with irreversible
      allograft damage from those associated with complete functional recovery (P =
      0.01). This study demonstrates that early evaluation of T cell proliferation in
      vitro identifies activated T cell infiltrates mediating acute cellular allograft
      rejection in a time frame suitable for clinical diagnostic application. It
      strengthens the concept that donor-specific cytotoxicity is governed by the
      stabilization of the alloantigen-T-cell receptor interaction by the accessory
      molecules CD4 and CD8, but either interaction is equally able to participate in
      an episode of acute rejection. Irreversible graft injury is associated with
      infiltrating cells that are capable of amplifying their responsiveness through
      secretion of IL-2.

PMID- 1371196
TI  - A three-year experience with serum anodal trypsinogen as a biochemical marker for
      rejection in pancreatic allografts. False positives, tissue biopsy, comparison
      with other markers, and diagnostic strategies.
AB  - Serum values of immunoreactive anodal trypsinogen (sAT) have been claimed to
      correlate well with rejection occurring in pancreatic allografts. We have studied
      the behavior of sAT in serial serum samples obtained from 39 type I diabetics
      undergoing whole-organ pancreas transplantation during the past 3 years. Patients
      had either received a pancreatic allograft simultaneously with a transplanted
      kidney (SPK, n = 33) or after a previous kidney transplant (pancreas after kidney
      [PAK] n = 6). The behavior of sAT was studied in relation to the clinical
      diagnosis of rejection. Graft amylase output for all 39 patients and serum
      creatinine for the 33 SPK recipients were also studied. Tissue biopsies were
      obtained from 11 patients with elevated sAT values and a presumptive diagnosis of
      rejection. Nine of these patients had SPK grafts and simultaneously elevated
      creatinine values. Tissue was obtained from the simultaneously transplanted
      kidney; all specimens revealed rejection. Two of the 11 patients had PAK
      allografts. Biopsies performed on the graft duodenum were consistent with acute
      rejection. Three additional patients with unchanged sAT values had biopsies for
      other reasons; these biopsies failed to demonstrate signs of acute rejection.
      Thus graft biopsy correlated exactly with sAT behavior in every case in which
      rejection was suspected. Five patients had elevations of sAT not associated with
      rejection: one resulted from direct trauma, two had outlet obstruction, and two
      had clinical diagnoses of graft pancreatitis. The sAT was more sensitive and
      specific than GAO and as sensitive as creatinine for SPK recipients. These
      studies confirm that sAT is a reliable, graft-specific biochemical marker for the
      early diagnosis of pancreatic rejection. The use of sAT should allow for the
      proper timing of graft biopsies and the judicious use of immunosuppressive
      agents, which will result in increased allograft survival for PAK and pancreas
      alone allografts.

PMID- 1371195
TI  - The adverse impact on liver transplantation of using positive cytotoxic
      crossmatch donors.
AB  - Because of the liver graft's ability to resist cytotoxic antibody-mediated
      rejection, it has become dogma that the conventional transplant crossmatch used
      to avoid hyperacute rejection of other organs is irrelevant to the liver. We
      examined this hypothesis in a consecutive series of adult primary liver
      recipients treated with FK506 and low-dose steroids. Twenty-five of 231 (10.8%)
      patients received a liver from a cytotoxic-positive crossmatch donor (more than
      50% of donor T lymphocytes were killed by dithiothreitol-pretreated recipient
      serum). The outcome was compared with that of 50 negative crossmatch patients who
      had their transplantations just before and after the crossmatch positive cases.
      The one-year graft and patient survivals were 56% and 68%, for positive and 82%
      and 86% for negative crossmatch patients (P = 0.004, P = 0.03, respectively). The
      difference between patient and first graft survival was accounted for by
      retransplantation, which was 4 times more frequent in the positive-crossmatch
      cases. Histologically, failed allografts obtained at the time of
      retransplantation revealed a spectrum of pathologic findings related to vascular
      injury. This study showed a higher difficulty of intraoperative blood product
      management, a degraded prognosis, and a poorer average quality of ultimate graft
      function when liver transplantation was performed against positive cytotoxic
      crossmatches. In such patients for whom crossmatch-negative donors may never be
      found because of the broad extent and intensity of sensitization, special
      therapeutic strategies perioperatively must be evolved if results are to improve.

PMID- 1371197
TI  - The induction of immunologic hyporesponsiveness by preoperative donor-specific
      transfusions and cyclosporine in human cadaveric transplants. A preliminary
      trial.
AB  - A prospective randomized preliminary trial was performed in patients undergoing
      cadaveric renal transplantation to determine the potential benefits,
      disadvantages, and logistic problems associated with the administration of donor
      specific transfusions and cyclosporine initiated 24 hr before transplantation.
      Ten patients received DST followed by continuous intravenous CsA approximately 24
      hr before cadaveric renal transplantation from the same donor. Twelve patients
      receiving sequential therapy with Minnesota antilymphoblast globulin,
      azathioprine, and steroids with subsequent conversion to CsA served as controls.
      Patient demographics and the donor characteristics were evenly matched in the two
      groups. While the study group had longer cold ischemia time and more evidence of
      renal dysfunction within the first two weeks, subsequent renal function was
      identical in the groups and there were fewer episodes of severe rejection
      requiring treatment with OKT3 within the first six months in the DST group (5 vs.
      0, P less than 0.05), which also had less reactivity in mixed lymphocyte cultures
      against preserved donor-specific lymphocytes than did the control group
      (stimulation index 9.0 +/- 3.0 vs. 25.3 +/- 6.0, respectively, P less than 0.05).
      The need for dialysis, incidence of infections and other complications, and
      subsequent immunosuppressive therapy were not different in the two groups. It is
      concluded that DSTs and intravenous CsA initiated 24 hr prior to transplantation
      are capable of inducing reduced immunologic responsiveness against the specific
      donor. Patients treated with this therapy should receive organs from "ideal"
      donors without risk factors and cold ischemia time should not exceed 30 hr.
      Further clinical studies of this approach are warranted.

PMID- 1371199
TI  - [Causes of pain and treatment effect in patients with cancer referred to a
      multidisciplinary pain clinic].
AB  - The causes of pain were analysed in 200 patients referred to a multidisciplinary
      pain clinic for cancer patients. In 158 patients, pain caused directly by tumour
      growth was found, 116 patients had pain secondary to the cancer disease or
      treatment while 33 patients had pain caused by factors unrelated to the cancer
      disease. The patients had many different combinations of causes of pain and the
      majority had more than one cause of pain. At the first contact and after
      treatment for 1-2 weeks, the patients were asked whether they had pain on
      movement, at rest or pain which interrupted sleep. After treatment for 1-2 weeks
      and after treatment for more than two weeks, the patients assessed the relief of
      pain obtained (none, slight, moderate, considerable, complete). The majority of
      patients achieved relief of pain at rest and during sleep while movement was
      still accompanied by pain in a number of patients. The majority of patients
      considered that the relief of pain obtained was moderate or considerable.
      Treatment consisted of adjustment of medication, blockades and epidural opioids
      supplemented by psychological intervention and help from social workers in
      selected patients.

PMID- 1371198
TI  - Inhibition of liver, kidney, and intestine regeneration by rapamycin.

PMID- 1371200
TI  - Benign prostatic hypertrophy.

PMID- 1371201
TI  - Renal transplantation for the nephrologist: new immunosuppressive drugs.

PMID- 1371202
TI  - Pain management on trial.

PMID- 1371203
TI  - Taming the overgrown prostate.

PMID- 1371204
TI  - Cytokeratin 20 in human carcinomas. A new histodiagnostic marker detected by
      monoclonal antibodies.
AB  - The authors have recently identified a new cytokeratin (CK) polypeptide, CK 20,
      whose expression is almost entirely confined to the gastric and intestinal
      epithelium, urothelium, and Merkel cells. Seven monoclonal antibodies (MAbs)
      specific for CK 20 were raised and characterized by applying immunoblotting and
      immunocytochemical screening. All of them reacted on frozen tissue sections. A
      further MAb, IT-Ks20.8, recognized CK 20 in sections of formalin-fixed, paraffin
      embedded tissue samples. A total of 711 cases of primary and metastatic cancer,
      mostly carcinomas, were analyzed immunohistochemically for CK-20 expression,
      using CK-20 specific guinea-pig antibodies and MAbs. The expression spectrum of
      CK 20 in carcinomas resembled that seen in the corresponding normal epithelia of
      origin. CK-20 positivity was seen in the vast majority of adenocarcinomas of the
      colon (89/93 cases), mucinous ovarian tumors, transitional-cell and Merkel-cell
      carcinomas and frequently also in adenocarcinomas of the stomach, bile system,
      and pancreas. Most squamous cell carcinomas in general and most adenocarcinomas
      from other sites (breast, lung, endometrium), nonmucinous tumors of the ovary,
      and small-cell lung carcinomas were essentially or completely negative. The
      authors propose to use CK 20 as a diagnostic marker valuable in distinguishing
      different types of carcinomas, notably when presenting as metastases.

PMID- 1371205
TI  - Changes in distribution, morphology, and tumor necrosis factor-alpha secretion of
      alveolar macrophage subpopulations during the development of bleomycin-induced
      pulmonary fibrosis.
AB  - Previous studies indicate that heterogeneous alveolar macrophages (AM) play a
      pivotal role in events associated with bleomycin-induced pulmonary fibrosis. A
      critical role has been suggested for tumor necrosis factor-alpha (TNF-alpha), a
      product of activated macrophages, in this fibrotic process. The present study
      examined whether the characteristics and function (TNF-alpha secretion) of rat AM
      subpopulations were altered during the development of bleomycin-induced fibrosis.
      After intratracheal bleomycin treatment, AM were separated into 18 density
      defined subpopulations. Bleomycin treatment altered the distribution and
      morphology of AM subpopulations of densities 1.017 to 1.061 g/ml at all time
      points studied (4, 14, and 28 days). Subpopulations of densities 1.090 to 1.141
      g/ml were affected only at 4 days after bleomycin treatment. Tumor necrosis
      factor-alpha secretion increased with time in 14- and 28-day samples of bleomycin
      treated rats, particularly in subpopulations of densities 1.075 to 1.097 g/ml.
      These data indicate that alterations in the distribution, morphology, and
      function of AM subpopulations accompany the development of bleomycin-induced
      pulmonary fibrosis. When coupled with previous studies suggesting that TNF-alpha
      plays a role in the fibrotic process in this disease model, these data indicate
      that AM of densities 1.075 to 1.097 g/ml are responsible for the production of
      TNF-alpha associated with bleomycin-induced pulmonary fibrosis.

PMID- 1371206
TI  - Choice of palliation for malignant hilar biliary obstruction.
AB  - Clinical data from 50 consecutive patients with unresectable hilar tumors
      situated at or proximal to the common hepatic duct were retrospectively analyzed
      to aid in the selection of appropriate palliative measures. Thirty-four patients
      had cholangioenteric bypass (CEB) to either left (28 patients), right (3
      patients), or both (3 patients) intrahepatic ductal systems. Sixteen patients had
      nonoperative drainage (NOD) established either endoscopically (4 patients),
      percutaneously (9 patients), or using a combined endoscopic-percutaneous approach
      (3 patients). When compared with patients with CEB, patients with NOD had more
      frequent medical problems (p less than 0.03) and lower serum albumin levels on
      admission (p less than 0.03). While comparable postprocedural complications (13
      CEB patients versus 4 NOD patients) were observed, patients with NOD had a
      significantly higher hospital mortality (9 CEB patients versus 9 NOD patients, p
      less than 0.05). Excluding the 12 patients (6 CEB patients versus 6 NOD patients)
      who died within 30 days after drainage, the quality of survival of the remaining
      38 patients was analyzed with reference to 6 objective parameters. Although
      patients with NOD had significantly more frequent admissions relating to their
      catheters (p less than 0.02), there was no qualitative difference in the survival
      rate between the two groups of patients. For selected high-risk patients with
      limited life expectancy, NOD should be offered. However, additional prospective
      studies are required to decide the best choice of palliation for patients who are
      not at such high risk.

PMID- 1371208
TI  - Endoscopic laser therapy for neoplastic lesions of the colorectum.
AB  - Surgical resection is the therapy of choice for most colorectal neoplasms.
      Endoscopic laser therapy (ELT) is a recently developed alternative for treatment
      of colorectal neoplasms and is applicable in a variety of clinical circumstances
      in which nonoperative treatment is preferable. The experience with ELT using the
      Nd:YAG (neodynium:yttrium-aluminum-garnet) laser in 42 patients was analyzed. The
      diagnosis was colorectal adenocarcinoma in 32 patients (76%) and neoplastic
      polyps in 10 (24%). ELT was undertaken either as a palliative treatment for
      malignant disease (60%), with curative intent for benign disease (26%), or as a
      temporizing measure (14%) in a total of 84 treatment sessions. Successful
      palliation or cure was achieved in 40 patients (95%) with 4 minor complications
      (9%) and no procedure-related deaths. This experience confirms ELT as an
      effective alternative to surgical therapy in the palliative, curative, or interim
      treatment of certain colorectal neoplasms in patients with prohibitive operative
      risk, limited anticipated survival, incurability, or diffidence toward operation.

PMID- 1371207
TI  - Relationship between pathologic prognostic factors and abnormal levels of des
      gamma-carboxy prothrombin and alpha-fetoprotein in hepatocellular carcinoma.
AB  - The relationship between pathologic prognostic factors and abnormal levels of des
      gamma-carboxy prothrombin and alpha-fetoprotein was investigated in 42 patients
      with resectable hepatocellular carcinoma. The frequencies of macroscopic massive
      type, intrahepatic metastasis, and portal vein tumor thrombus were significantly
      higher in patients with positive des-gamma-carboxy prothrombin (p less than 0.05)
      but not with alpha-fetoprotein. Other histologic factors in tumorous and
      nontumorous tissues were not significantly different irrespective of the
      positivity of these markers. In patients with tumors not more than 6 cm in
      diameter, the frequency of intrahepatic metastasis was positively correlated with
      the positivity of des-gamma-carboxy prothrombin (p less than 0.05) and inversely
      with that of alpha-fetoprotein (p less than 0.05). Furthermore, intrahepatic
      metastasis was most frequently observed in patients with positive des-gamma
      carboxy prothrombin and negative alpha-fetoprotein (eight of nine) and least
      frequently in cases with negative des-gamma-carboxy prothrombin and positive
      alpha-fetoprotein (one of eight). These findings indicated that both des-gamma
      carboxy prothrombin and alpha-fetoprotein might be useful markers for the
      prediction of intrahepatic spread of hepatocellular carcinoma.

PMID- 1371209
TI  - In vitro activation of bronchoalveolar lavage cells by house dust mite allergens.
AB  - Mast cells represent a small but important proportion of bronchoalveolar lavage
      cells and are directly exposed to environmental triggers including allergens.
      Histamine and PGD2 are mediators released during the activation of mast cells.
      Fourteen patients allergic to Dermatophagoides pteronyssinus were studied. After
      bronchoalveolar lavage the unfractionated cell pellet containing metachromatic
      cells was submitted to allergen challenge using three concentrations of a
      standardized Dermatophagoides pteronyssinus extract and one concentration of
      A23187 (2.5 microM). The release of histamine was measured by radioimmunoassay
      using a monoclonal antibody against acylated histamine and PGD2 was measured by
      enzyme immunoassay using a polyclonal antibody against methoxamine-PGD2.
      Histamine was released in 13/14 patients following stimulation of the cells with
      A23187 and 12/14 patients after stimulation with Dermatophagoides pteronyssinus
      extract. The release of histamine was 3.5-fold greater when cells were stimulated
      by the Dermatophagoides pteronyssinus extract than with A23187. PGD2 was released
      in 10/12 patients when cells were stimulated with A23187 and 6/14 patients in the
      case of Dermatophagoides pteronyssinus extract stimulation. In the latter case,
      the mean release was not significantly greater than baseline. For histamine, the
      maximum release usually occurred with the more concentrated extract whereas in
      the experiments where PGD2 was released, maximal generation usually occurred with
      the lowest concentration used. There was no correlation between the severity of
      asthma and the release of mediators. This study confirms the activation of
      metachromatic cells by allergen and shows some heterogeneity in the release of
      granule and membrane-derived mediators.

PMID- 1371210
TI  - Effect of dehydration on cardiovascular responses and electrolytes after
      hypertonic saline/dextran treatment for moderate hemorrhage.
AB  - STUDY OBJECTIVE: To determine if hypertonic saline/dextran (HSD) is effective in
      treating hemorrhage in the presence of dehydration. DESIGN: After surgical
      preparation, swine were euhydrated or dehydrated for 24 or 48 hours. Animals were
      bled 25 mL/kg over 60 minutes and treated with HSD. SETTING: Laboratory.
      PARTICIPANTS: Seventeen immature Yorkshire pigs. INTERVENTIONS: 4 mL/kg HSD (7.5%
      NaCl in 6% dextran-70) administered over one minute. MEASUREMENTS AND MAIN
      RESULTS: All euhydrated animals survived; 100% of the pigs survived 180 minutes
      after treatment. Two animals dehydrated for 24 hours and three animals dehydrated
      for 48 hours died within three hours of HSD treatment. In all groups, plasma
      potassium was reduced significantly and equally; cardiac output was increased;
      mean arterial pressure rose rapidly within first five minutes, but was sustained
      only in euhydrated animals; hematocrit, hemoglobin, and plasma total protein
      levels were reduced; and plasma glucose increased with persistent between-group
      differences. RESULTS: HSD immediately rectified the decreases in mean arterial
      pressure and cardiac output incurred during hemorrhage; over time, however, the
      improvement in pressure was not sustained in dehydrated pigs. Parallel increases
      in plasma osmolality and sodium concentrations were offset by the initial group
      differences resulting from dehydration. CONCLUSION: Dehydration does not
      compromise the efficacy of HSD as a resuscitation treatment for hemorrhagic
      shock.

PMID- 1371212
TI  - Studies on complement deposits in epidermolysis bullosa acquisita and bullous
      pemphigoid.
AB  - Epidermolysis bullosa acquisita (EBA) is an inflammatory subepidermal blistering
      disease characterized by circulating and tissue-bound autoantibodies specific for
      type VII collagen of the basement membrane zone. The antibodies consist of both
      complement- and noncomplement-binding populations and belong to all four
      subclasses of IgG. We investigated the presence of the membrane attack complex
      C3b, C5, and S protein in EBA and compared C3b and C5 in EBA and bullous
      pemphigoid. In 10 patients with EBA, these components were detected at the
      basement membrane zone as follows: membrane attack complex, 90%; S protein, 90%;
      direct C5, 90%; C3b, 100%; and C5 binding, 90%. In the patients with bullous
      pemphigoid, the results were as follows: direct C5, 58%; C3b, 33%; and C5
      binding, 19%. These results provide additional evidence for complement activation
      at the basement membrane zone in EBA, show that complement activation in EBA
      proceeds to activation of terminal complement components, and suggest that EBA
      antibodies are more potent activators of C5 than are bullous pemphigoid
      antibodies.

PMID- 1371211
TI  - Treatment of progressive membranous glomerulopathy. A randomized trial comparing
      cyclophosphamide and corticosteroids with corticosteroids alone. The Glomerular
      Disease Collaborative Network.
AB  - OBJECTIVE: To determine if deterioration in renal function could be ameliorated
      by adding cyclophosphamide to corticosteroid therapy in patients with progressive
      membranous glomerulopathy. DESIGN: Randomized, controlled treatment trial.
      Patients were followed for a mean of 29.2 +/- 17.1 months. SETTING: Collaborative
      network of 120 university and private-practice nephrologists. PARTICIPANTS:
      Patients with membranous glomerulopathy whose renal function deteriorated (as
      evidenced by doubling of the serum creatinine level, a 50% fall in the glomerular
      filtration rate, or a sustained serum creatinine level of greater than 2.0 mg/dL
      [reciprocal creatinine value, 0.5], or whose nephrotic range proteinuria
      persisted in association with morbid complications. Of 156 patients with biopsy
      proven membranous glomerulopathy, 36 became eligible for randomization. Twenty
      six of these 36 patients were randomly assigned to receive one of the two
      treatments. INTERVENTIONS: Pulse methylprednisolone, oral corticosteroids, and 6
      months of intravenous cyclophosphamide or alternate-day corticosteroid therapy
      alone. MAIN RESULTS: At entry, no statistical differences were found between the
      treatment groups in duration of renal disease, age, gender, serum creatinine
      level, 24-hour urine protein excretion, or biopsy stage. The groups showed no
      difference in mean arterial blood pressure during follow-up. Four of the 13
      patients receiving corticosteroids alone and 4 of the 13 patients receiving
      corticosteroids plus intravenous cyclophosphamide progressed to end-stage renal
      disease during follow-up. Reciprocal creatinine values tested at 6-month
      intervals showed no statistical differences between treatment groups at any time
      point. The log of the 24-hour protein excretion values showed no statistical
      differences between treatment groups after treatment. The power to detect a
      substantial improvement in renal function, defined as a doubling of the
      reciprocal of the serum creatinine, at the 0.05 significance level was 0.92.
      CONCLUSIONS: Combination therapy with intravenous cyclophosphamide and
      corticosteroids, when compared with corticosteroid therapy alone, does not
      improve renal function in patients with progressive membranous glomerulopathy.

PMID- 1371214
TI  - Comparison of growth kinetics of producing and nonproducing hybridoma cells in
      batch culture.
AB  - Several clones of nonproducing cells were isolated from a continuous culture of
      hybridoma cells, which were originally producing antibody. Their behavior was
      compared to that of the producing cells in batch culture. The growth kinetics of
      five out of six clones exhibited higher specific growth rate, higher yield of
      cell mass on glutamine, and lower yields of lactate and ammonium. The
      implications of the comparisons for growth of hybridoma cultures are discussed.

PMID- 1371213
TI  - Synthesis and characterization of 7-nitrobenzo-2-oxa-1,3-diazole (NBD)-labeled
      fluorescent opioids.
AB  - Alkylation of sarcosine with 4-chloro-nitrobenzo-2-oxa-1,3-diazole (NBD-chloride)
      furnished a fluorescent tag that was coupled with a tetrahydrothebaine derivative
      and beta-naltrexamine, respectively, to yield the fluorescent opioids 7 alpha
      (1R)-1-hydroxy-1-methyl-3-(4-hydroxyphenyl)-propyl]-6,14-
      endoethenotetrahydrothebaine NBD-sarcosinate (ASM-5-10) and N-cyclopropylmethyl-3
      hydroxy-14 beta-hydroxy-6 beta-(NBD sarcosinyl)-amino-epoxymorphinan (ASM-5-67).
      The fluorescence intensity of the novel opioids allowed their detection at
      subnanomolar concentrations, and was dependent on the polarity of the solvent.
      Maximum quantum yield was obtained in ethyl acetate and ethanol, and minimal
      fluorescence in heptane and water. Compounds ASM-5-10 and ASM-5-67 displaced the
      opioid receptor binding of [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol in monkey brain
      membranes with IC50 values of 8.4 and 1.5 nM, respectively. Whereas ASM-5-67
      bound to mu, delta, and kappa receptors with comparable affinities, ASM-5-10 was
      mu-selective, with selectivity indices (ratio of respective IC50 values) of 0.04
      for both mu/delta and mu/kappa. The sodium response ratio in binding revealed a
      pronounced agonist property of ASM-5-10. Both opioids were lipophilic, with
      octanol-water partition coefficients (log Papp) of 2.8 (ASM-5-10) and 1.0 (ASM-5
      67). ASM-5-10 exhibited particularly strong membrane retention that was not
      reversible by four washes. Their favorable characteristics in fluorescence,
      receptor binding, and membrane interaction make these newly developed ligands
      useful molecular probes to study opioid receptor mechanisms.

PMID- 1371215
TI  - Social skills and their correlates: preschoolers with developmental delays.
AB  - Fifteen preschool-age children with mild mental retardation (developmental
      delays) from mainstreamed schools were observed during two structured play
      sessions with matched peers without mental retardation. Children with
      developmental delays spent more time alone and when they played, showed less
      social play. The two groups did not differ on communication behaviors that
      maintained play or in negative affect; however, the children with developmental
      delays evidenced more disruptive entry, more regressive behaviors, and less
      positive affect. Families were interviewed concerning their attitudes about, and
      teaching of, social skills. For the children without mental retardation, level of
      social play was positively related to the family's teaching and the child's
      communication abilities. For the children with delays, social play related to
      developmental age and communication ability but not to family teaching.

PMID- 1371216
TI  - The role of nitric oxide in hippocampal long-term potentiation.
AB  - Long-term potentiation is a long-lasting, use-dependent increase in the strength
      of synaptic connections. We investigated the role of nitric oxide (NO) in
      determining the duration of potentiation induced by high frequency stimulation of
      afferents in the CA1 region of the rat hippocampus. The calcium/calmodulin
      dependent production of NO can be initiated by activation of excitatory amino
      acid receptors and results in increased levels of cGMP in target cells. Here we
      report that only a relatively short-term potentiation can be induced in the
      presence of nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor. The
      effects of L-NAME on the duration of potentiation are partially reversed by
      coadministration of L-arginine, a precursor of neuronal NO, and by dibutyryl
      cGMP. Hemoglobin, which binds extracellular NO, also shortens the duration of
      stimulus-induced potentiation. The results suggest a role for NO in the
      maintenance of activity-dependent synaptic enhancements, possibly via the
      generation of cGMP.

PMID- 1371218
TI  - Loss of extrasynaptic channel modulation by protein kinase C underlies the
      selection of serotonin responses in an identified leech neuron.
AB  - Pressure-sensitive (P) neurons contacted by serotonergic Retzius (R) neurons of
      the leech in culture selectively reduce a protein kinase C (PKC)-dependent cation
      response to serotonin and are innervated by the inhibitory, Cl(-)-dependent
      synapse seen in vivo. We have examined whether the reduction of extrasynaptic
      cation channel modulation is due to changes in sensitivity of the channels to
      second messenger. In inside-out membrane patches from single, uncontacted P cells
      in culture, cation channel activity was increased by rat brain PKC and cofactors.
      In contrast, the activity of cation channels in patches isolated from P cells
      paired with R cells was unaffected by PKC. These results demonstrate the loss of
      extrasynaptic channel modulation by PKC during synapse formation.

PMID- 1371219
TI  - Isoform-selective deficit of glycine receptors in the mouse mutant spastic.
AB  - The mutant mouse spastic (spa) develops a characteristic motor disorder about 2
      weeks after birth, with symptoms resembling sublethal poisoning by the
      glycinergic antagonist strychnine. Correspondingly, adult homozygotic mutants
      (spa/spa) exhibit a severe reduction of inhibitory glycine receptors in spinal
      cord and brain. Here we show that the spastic mutation selectively interferes
      with the postnatal accumulation of the adult isoform of the glycine receptor
      protein, whereas perinatal expression of the neonatal receptor isoform is not
      detectably affected. Heterologous expression in X. laevis oocytes of poly(A)+ RNA
      and Northern blot analysis indicate normal levels of glycine receptor alpha 1
      subunit transcripts in spinal cord of adult spastic mutants. Thus, the age
      dependent manifestation of spastic symptoms after birth reflects a selective
      effect of the mutation on the developmental expression of the adult glycine
      receptor isoform.

PMID- 1371217
TI  - Cloning of a putative glutamate receptor: a low affinity kainate-binding subunit.
AB  - Kainate, a glutamate receptor agonist, is a potent neuroexcitatory agent that
      produces epileptiform activity and selective neuronal degeneration. Binding
      studies using neuronal membrane homogenates or brain sections have identified
      sites having either high or low affinity for [3H]kainate. Here we report the
      cloning of a gene, GluR7, with approximately 75% sequence identity with the
      previously cloned GluR5 and GluR6 subunit genes. Transcripts of the GluR7 gene
      are evident in brain areas that bind [3H]kainate and are susceptible to kainate
      induced neurotoxicity. We have performed ligand binding studies with membranes of
      transfected HeLa cells expressing GluR6 or GluR7 subunits. Our data show that the
      GluR6 and GluR7 subunits have a rank order of agonist affinity (domoate greater
      than kainate much greater than L-glutamate, quisqualate much greater than AMPA,
      NMDA) and a dissociation constant for kainate (95 and 77 nM, respectively)
      characteristic of the low affinity kainate-binding sites described in the brain.

PMID- 1371221
TI  - QT dispersion in sinus beats and ventricular extrasystoles in normal hearts.
AB  - OBJECTIVE: Recent studies have suggested that QT interlead variability
      (dispersion) on the surface electrocardiogram may have potential as a measure of
      recovery time dispersion. To test this hypothesis further QT dispersion occurring
      in sinus beats was compared with that in ventricular extrasystoles. DESIGN:
      Simultaneous electrocardiograms were recorded at 50 mm/s during sinus rhythm in a
      drug free state while ventricular extrastimuli were introduced by programmed
      right ventricular stimulation at different coupling intervals. QT dispersion,
      defined as the difference between the maximum and minimum QT, was calculated
      separately for the extrasystoles and preceding and following sinus complexes. To
      correct for the influence of the number of measurable leads on QT dispersion, an
      "adjusted" QT dispersion calculated as QT dispersion/square root of the number of
      measurable leads, was used to compare sinus complexes and extrasystoles.
      PATIENTS: Nine patients were studied who were undergoing electrophysiological
      study for investigation of palpitation and were found to have electrically normal
      ventricles. RESULTS: At all coupling intervals tested "adjusted" QT dispersion
      was significantly greater in the ventricular extrasystoles than in either the
      preceding or following sinus complexes. For the coupling interval 350 ms, the 95%
      confidence intervals for the difference between means was 52 to 78 ms (preceding
      sinus complex) and 56 to 82 ms (following sinus complex) (p less than 0.00001).
      There was no correlation between the coupling interval and the magnitude of the
      "adjusted" QT dispersion. CONCLUSION: These results accord fully with expected
      differences in ventricular recovery time dispersion and offer further support for
      the hypothesis that QT dispersion reflects regional variation in ventricular
      recovery. If substantiated by invasive studies, these findings have wide
      implications for both the usefulness and the method of QT measurement.

PMID- 1371220
TI  - Temporal and spatial modulation of a cytoskeletal antigen during peripheral
      axonal pathfinding.
AB  - A neuron-specific cytoskeletal antigen (5E10), whose expression pattern during
      initial motoneuron outgrowth into the chick limb suggests that it is playing a
      role in axon guidance, is described. This antigen, which was shown to be a
      phosphorylated epitope, probably of the intermediate weight neurofilament protein
      (NF-M), exhibits a highly stereotyped and spatially heterogeneous pattern of
      expression. The point of onset of expression, which was abrupt and occurred in
      the distal axon and base of the growth cone, differed between groups of neurons
      that projected to different targets. Specifically, expression occurred from
      positions where previous perturbation experiments suggested that the axons in
      question would begin responding to specific guidance cues, and it remained high
      along the axon from this point to the target. Expression of this antigen could
      also be induced in cultured motoneurons by activating several second messenger
      systems.

PMID- 1371222
TI  - Antinuclear antibodies: clinical correlations and biologic significance.
AB  - Several trends become evident from the foregoing discussion. As the different ANA
      antigenic specificities have been identified, they have often been found to be
      highly conserved polypeptides that subserve very basic cellular functions that
      are carried out in the nucleus, nucleolus, and ribosomes. The reasons why only 30
      or so basic cellular proteins become the targets of an autoimmune response in
      patients with connective tissue disease at the exclusions of the other 10,000
      macromolecules that exist inside cells remain a mystery. However, some insight
      into this enigma might be provided by the mechanism of molecular mimicry (Table
      9). The possibility that highly conserved immunogenic molecules that are
      expressed by infectious pathogens can trigger an immune response in a genetically
      predisposed human host that cross-reacts with cellular autoantigens is a well
      documented phenomenon in disorders such as rheumatic fever. This mechanism is now
      being mentioned with increasing frequency in discussions pertaining to the
      pathogenesis of autoimmune connective tissue diseases. Another trend relates to
      the increasing sensitivity of the newer assays that have been developed to detect
      ANA. When highly purified or recombinant autoantigens are used in versatile
      assays such as ELISA, radioimmunoassays, or immunoprecipitation, the frequency
      with which certain autoantibodies can be detected in patient subgroups can go up
      significantly. For example, with classical immunodiffusion, anti-Ro/SS-A
      antibodies can be detected in 25% of unselected patients with SLE, whereas with
      an ELISA based on affinity purified Ro/SS-A antigen, 50% of patients with SLE are
      found to have elevated levels of this autoantibody specificity. As is often the
      case, we pay for increased sensitivity in a laboratory test with decreased
      specificity. With immunodiffusion, virtually no normal individuals have anti
      Ro/SS-A antibodies, but with the ELISA as many as 10% of normals have elevated
      anti-Ro/SS-A binding levels. Thus, the incremental diagnostic value of this newer
      anti-Ro/SS-A assay could be questioned. The true clinical value of this new
      laboratory technology will become more evident when these more sophisticated ANA
      assays are used together in a panel-like fashion to profile a given patient's
      autoimmune response at the very onset of his illness. Preliminary work has
      already begun in this area. This approach, if well standardized, could have
      significant diagnostic and prognostic value. Another benefit of this newer
      technology will be the ability to measure antibody binding levels to individual
      autoepitopes--limited portions of an autoantigen's amino acid sequence that
      represent single antibody binding sites. It is possible that certain patterns of
      clinical disease could be linked to autoantibody production against individual
      autoepitopes rather than whole autoantigenic molecules. This area is only now
      beginning to be explored.

PMID- 1371223
TI  - Quality and cost in the palliative care of cancer.

PMID- 1371224
TI  - Dual appearance of fluorescein staining in vivo of diseased human corneal
      epithelium. A non-contact photomicrographic study.
AB  - Adherence of fluorescein sodium dye to diseased epithelial cells, a hitherto
      unreported phenomenon, was captured in photomicrographs in severe herpes zoster
      and keratoconjunctivitis sicca keratopathies. It is notable that this phenomenon
      differs completely from the well known fluorescent property of the dye
      penetrating into defective corneal epithelium, and that the staining pattern
      shown by adherent fluorescein correlates well with the staining pattern shown by
      rose bengal dye.

PMID- 1371225
TI  - Controlled trial of laser photocoagulation of pigment epithelial detachments in
      the elderly: 4 year review.
AB  - Patients who were enrolled in a controlled treatment trial of laser grid
      photocoagulation for retinal pigment epithelial detachment as part of age-related
      maculopathy were reviewed 4 years after entry into the trial. The data imply that
      the original conclusion that this form of treatment did not improve the visual
      prognosis at 18 months was also justified at 4 years. It has become clear that
      lesions with evidence of subpigment epithelial new vessels were included in the
      trial. In a retrospective study the lesions were separated into those in which
      there was evidence of subretinal neovascularisation and those in which no such
      evidence existed. A difference was identified in the behaviour of the treated and
      untreated lesions designated avascular in that the treated eyes had a poorer
      visual outcome. These cases accounted for the different behaviour between two
      management groups in the initial study such that the original conclusion that
      grid photocoagulation of avascular pigment epithelial detachments in the elderly
      does not improve the visual prognosis is justified.

PMID- 1371226
TI  - Detection of subpigment epithelial neovascularisation in cases of retinal pigment
      epithelial detachments: a review of the Moorfields treatment trial.
AB  - The entry angiograms of 42 eyes with detachment of the retinal pigment epithelium
      in a treatment trial of laser photocoagulation were reviewed in a masked fashion
      by three observers in order to assess the possible presence of subpigment
      epithelial neovascularisation. Vascularity or avascularity was designated with
      reference to a list of clues believed to imply the presence of subpigment
      epithelial neovascularisation. As a predictor of outcome the initial assessment
      achieved a sensitivity and specificity of 77% and 82% respectively. Despite
      notable parity of the degree of sensitivity and specificity among the three
      observers, full agreement on the initial assessments was reached in only 23 eyes
      (55%), 10 with vascular and 13 with avascular outcome. Of these, only one eye
      which developed new vessels after 4 years had an outcome which differed from that
      predicted by classification of the entry angiograms.

PMID- 1371227
TI  - Biological activities of vitreous gel, retrohyaloid fluid and subretinal fluid
      from diabetic and non-diabetic eyes.
AB  - This study compared the effects of vitreous gel, retrohyaloid fluid and
      subretinal fluid from diabetic and non-diabetic eyes on the proliferation and
      migration of retinal microvascular cells in vitro. Intraocular fluids were
      obtained from eyes undergoing repair of retinal detachment, due either to
      proliferative diabetic retinopathy or rhegmatogenous retinal detachment
      associated with a degree of proliferative vitreoretinopathy. The results
      demonstrated that the intraocular stimulatory activity for the proliferation of
      retinal microvascular endothelial cells varied between the different ocular
      compartments. The mitogenic and migrational activity in vitreous gel was greater
      than that of either the subretinal or retrohyaloid fluids of the same eye, and
      the activity of subretinal fluid was intermediate between that of the vitreous
      gel and the retrohyaloid fluid. There was no significant difference between the
      activities of the samples from diabetic and non-diabetic eyes.

PMID- 1371228
TI  - Preparation and characterization of monoclonal antibodies against 4-aminobenzoate
      hydroxylase from Agaricus bisporus.
AB  - A monoclonal antibody (mAb, A) recognizing the FAD-binding domain of 4
      aminobenzoate hydroxylase (4-aminobenzoate, NAD(P)H:oxygen oxidoreductase (1
      hydroxylating, decarboxylating), EC 1.14.13.27) from Agaricus bisporus, a common
      edible mushroom, had been produced (Tsuji, H., Ogawa, T., Bando, N., Kimoto, M.
      and Sasaoka, K. (1990) J. Biol. Chem. 265, 16064-16067). In the present study,
      three other mAbs (B1, B2 and B3) against the enzyme have been further prepared in
      order to facilitate the structural characterization of the enzyme. The three new
      mAbs immunoblotted the enzyme. The four mAbs, including A, were specific for
      different epitopes on the enzyme. B1 and B2 immunoprecipitated the apoenzyme and
      the immunoprecipitation was inhibited in the presence of FAD, whereas B3 failed
      to immunoprecipitate the apoenzyme in the absence or presence of FAD. B1 and B2
      competed with FAD for the binding to the apoenzyme. These findings show that B1
      and B2 recognize the FAD-binding domain of the enzyme in analogy with A. The
      immunoblotting analyses of the peptides obtained from the enzyme by digestion
      with lysyl endopeptidase (EC 3.4.21.50) provided useful knowledge as to the
      location of the epitopes to the mAbs on the enzyme, suggesting that the FAD
      binding domain of the enzyme can be located and characterized by detailed
      investigations on the location of the epitopes.

PMID- 1371229
TI  - Generation of one set of monoclonal antibodies specific for b-pathway ganglio
      series gangliosides.
AB  - We established six murine monoclonal antibodies (MAbs) specific for b-pathway
      ganglio-series gangliosides by immunizing C3H/HeN mice with these purified
      gangliosides adsorbed to Salmonella minnesota mutant R595. The binding
      specificities of these MAbs were determined by an enzyme-linked immunosorbent
      assay and immunostaining on thin-layer chromatogram. These six MAbs, designated
      GGB19, GMR2, GMR7, GGR12, GMR5, and GGR13 reacted strongly with the gangliosides
      GD3, O-Ac-GD3, GD2, GD1b, GT1b, and GQ1b, respectively, that were used as
      immunogens. All these MAbs except GGB19 showed highly restricted binding
      specificities, reacting only with the immunizing ganglioside. None of other
      various authentic gangliosides or neutral glycolipids were recognized. On the
      other hand, MAb GGB19 exhibited a broader specificity, cross-reacting weakly with
      O-Ac-GD3, GQ1b, and GT1a, but not with other gangliosides or neutral glycolipids.
      Using these MAbs, we determined the expression of these gangliosides, especially
      GD1b, GT1b, and GQ1b on mouse, rat, and human leukemia cells. GD1b was expressed
      on rat leukemia cells, but not on mouse and human leukemia cells tested. Neither
      GT1b nor GQ1b was detected in these cell lines.

PMID- 1371230
TI  - Appropriate chemotherapy for palliating advanced cancer.

PMID- 1371231
TI  - Appropriate chemotherapy for palliating advanced cancer.

PMID- 1371232
TI  - Primary treatment of pelvic osteosarcoma. Report of five cases.
AB  - Five patients, ages 12 to 20 years, with nonresectable primary (Patients 2, 3,
      and 5) and metastatic (Patients 1 and 4) pelvic osteosarcomas were treated with
      intraarterial cisplatin and concurrent radiation therapy from 1983 to 1987. Long
      term local tumor control was achieved in all five patients. Patients 1 and 3 are
      alive with no evidence of local recurrence or metastatic disease at 77 and 56
      months of follow-up, respectively, since diagnosis of the pelvic tumor. Patients
      2, 4, and 5 died of metastatic lung disease at 25, 39, and 12 months,
      respectively, after diagnosis of the pelvic tumor. Patient 4 had no clinical or
      radiologic evidence of local recurrence. Control of tumor growth in patients with
      pelvic osteosarcomas can be achieved with regional chemotherapy and concurrent
      radiation therapy. These patients also should receive adjuvant intensive systemic
      chemotherapy to increase the probability of eliminating potential subclinical
      metastatic disease.

PMID- 1371233
TI  - The relationship of prostate-specific antigen to digital rectal examination and
      transrectal ultrasonography. Findings of the American Cancer Society National
      Prostate Cancer Detection Project.
AB  - The participating institutions of the American Cancer Society National Prostate
      Cancer Detection Project did 520 biopsies on 2425 men over a 3.5-year period. A
      total of 88 cancers were confirmed pathologically, 93% of which clinically were
      organ confined. In 324 men (62.3%), a recommendation for biopsy was made based
      solely on the results of transrectal ultrasonography (TRUS); in 69 patients
      (13.3%), solely on the digital rectal examination (DRE); in 116 patients (22.3%),
      on abnormal DRE and TRUS examinations; and in 11 patients (2.1%), in whom DRE and
      TRUS were normal, on elevated prostate-specific antigen (PSA) levels. The TRUS
      was abnormal in 80.6% of men found to have cancer, and the PSA level and DRE were
      abnormal for 67% and 50% of cancers, respectively. The influence of PSA level on
      cancer detection increased as the serum level increased above 4 ng/ml. The
      positive predictive values of both the DRE and TRUS were influenced significantly
      by the presence of an elevated PSA level (P = 0.044 and P less than 0.001,
      respectively). The results of this ongoing multicenter study support the
      following statements: (1) the prostate cancer detection rate is influenced by
      this diagnostic triad and (2) the detection rate of organ-confined disease can be
      improved substantially by early detection programs.

PMID- 1371234
TI  - Prostate-specific antigen levels in 1695 men without evidence of prostate cancer.
      Findings of the American Cancer Society National Prostate Cancer Detection
      Project.
AB  - The American Cancer Society National Prostate Cancer Detection Project is a
      prospective, multidisciplinary, and multicenter trial to assess the potential for
      early detection of prostate cancer by transrectal ultrasonography (TRUS), digital
      rectal examination (DRE), and serum prostate-specific antigen assay (PSA). By
      November 1990, 2805 men between the ages of 55 and 70 years with no known signs
      or symptoms of prostate cancer were enrolled in the study, which is planned to
      run for 5 years. Annual TRUS, DRE, and PSA tests were done on these subjects, and
      biopsies were recommended for suspicious lesions when detected. To study the
      performance of PSA testing in presumed normal subjects, all men were eliminated
      who had (1) prostate cancer detected on their initial examinations and proven by
      biopsy or (2) cancer detected during the year or subsequent examinations.
      Additionally, all men with TRUS or DRE findings that were interpreted as
      suspicious for cancer but who are being followed and have not yet had biopsies
      done were removed from this series. This left a unique, extensively screened
      group of 1695 men who were free of prostate cancer, as far as could be
      determined. Analyses of the PSA levels in this large population in the
      appropriate age range for increasing risk of prostate cancer revealed several
      important findings. First, there was a direct relationship between serum PSA
      levels and estimated prostate volume for both the currently available monoclonal
      and polyclonal PSA assays. Individuals with benign prostatic hyperplasia and
      larger gland volume have a higher normal limit of PSA than men with normal gland
      volume. Second, analyses showed no relationship between age and PSA levels or
      between symptoms of prostatism and PSA levels independent of gland enlargement.
      It was concluded that volume-adjusted upper limits of normal PSA can be
      determined for different levels of specificity desired. This information may be
      applicable to the use of PSA in men not already suspected of having prostate
      cancer and may increase its effectiveness as a tool for early detection.

PMID- 1371235
TI  - Hyperthyroidism in men with germ cell tumors and high levels of beta-human
      chorionic gonadotropin.
AB  - A retrospective review was done on all high volume choriocarcinomas and other
      germ cell tumors of men with serum beta-human chorionic gonadotropin (beta-HCG)
      levels greater than 50,000 mIU/ml to determine the incidence and characteristics
      of hyperthyroidism in this setting. Nineteen patients were identified with high
      beta-HCG levels, but because 2 did not have thyroid function tests performed, the
      cases of only 17 patients were evaluable. Of these, 14 (82%) had primary
      testicular carcinoma and 3 (18%) had extragonadal tumors. Beta-HCG levels on
      presentation ranged from 80,000 to 3,058,000 mIU/ml, with a median of 243,500
      mIU/ml. Seven of the 17 evaluable cases (41%) had T4 serum levels higher than 12
      micrograms/dl (normal level 4 to 12 micrograms/dl) with a median value of 15.4
      micrograms/dl (range, 12.6 to 33.5 micrograms/dl); serum T4 levels correlated
      with beta-HCG levels (r = 0.84). All seven patients with elevated T4 levels had
      beta-HCG values greater than 200,000 mIU/ml, and three of these seven had
      clinical manifestations that could be attributed to an elevated serum T4; only
      one patient required specific antithyroid treatment; and after control of primary
      disease, all other patients had normalization of thyroid function. The most
      common manifestations of hyperthyroidism in our series were tachycardia,
      hypertension, and a systolic flow murmur; none of the patients had thyroid gland
      enlargement. We conclude that subclinical hyperthyroidism is a relatively common
      phenomenon in germ cell tumors of men with high levels of beta-HCG and that
      control of the primary disease results in serum T4 level normalization.

PMID- 1371236
TI  - The right ventricle in congenital heart disease.
AB  - An increasing number of children with congenital heart disease are surviving into
      adulthood, creating new, unusual patients with different physiologic and anatomic
      problems for the adult cardiologist. This article discusses those lesions
      affecting primarily the right ventricle.

PMID- 1371237
TI  - Local modulation of neurofilament phosphorylation, axonal caliber, and slow
      axonal transport by myelinating Schwann cells.
AB  - Studies in Trembler and control mice demonstrated that myelinating Schwann cells
      exert a profound influence on axons. Extensive contacts between myelin and axons
      have been considered structural. However, demyelination decreases neurofilament
      phosphorylation, slow axonal transport, and axonal diameter, as well as
      significantly increasing neurofilament density. In control sciatic nerves with
      grafted Trembler nerve segments, these changes were spatially restricted: they
      were confined to axon segments without normal myelination. Adjacent regions of
      the same axons had normal diameters, neurofilament phosphorylation, cytoskeletal
      organization, and axonal transport rates. Close intercellular contacts between
      myelinating Schwann cells and axons modulate a kinase-phosphatase system acting
      on neurofilaments and possibly other substrates. Myelination by Schwann cells
      sculpts the axon-altering functional architecture, electrical properties, and
      neuronal morphologies.

PMID- 1371238
TI  - The human class II MHC protein HLA-DR1 assembles as empty alpha beta heterodimers
      in the absence of antigenic peptide.
AB  - We have produced the human class II histocompatibility protein, HLA-DR1, as a
      soluble, secreted glycoprotein in insect cells infected with baculoviruses
      carrying truncated alpha and beta subunit genes. The peptide-binding site is
      empty, and the empty molecules are fully competent to bind antigenic peptide. We
      used the empty molecules to measure an intrinsic rate for peptide association,
      and to investigate the role of peptide in stabilizing the class II structure.
      Peptide binding kinetics for the empty molecule are only 10-fold faster than for
      peptide exchange into an occupied site, suggesting that a conformational change
      may accompany peptide binding. The native alpha beta heterodimer assembles in the
      absence of antigenic peptide, but peptide binding stabilizes the empty
      heterodimer against aggregation and against SDS-induced denaturation.

PMID- 1371239
TI  - Purification and functional reconstitution of the cystic fibrosis transmembrane
      conductance regulator (CFTR).
AB  - Circumstantial evidence has accumulated suggesting that CFTR is a regulated low
      conductance Cl- channel. To test this postulate directly, we have purified to
      homogeneity a recombinant CFTR protein from a high-level baculovirus-infected
      insect cell line. Evidence of purity included one- and two-dimensional gel
      electrophoresis, N-terminal peptide sequence, and quantitative amino acid
      analysis. Reconstitution into proteoliposomes at less than one molecule per
      vesicle was accomplished by established procedures. Nystatin and ergosterol were
      included in these vesicles, so that nystatin conductance could serve as a
      quantitative marker of vesicle fusion with a planar lipid bilayer. Upon
      incorporation, purified CFTR exhibited regulated chloride channel activity,
      providing evidence that the protein itself is the channel. This activity
      exhibited the basic biophysical and regulatory properties of the type of Cl-
      channel found exclusively in CFTR-expressing cell types and believed to underlie
      cAMP-evoked secretion in epithelial cells.

PMID- 1371240
TI  - The existence of two completely distinct antigenic sites within a decapeptide.
AB  - A decapeptide (1182-1191) derived from the bovine interphotoreceptor retinoid
      binding protein (IRBP) was found to contain two completely distinct antigenic
      sites when tested in Lewis rats. One site, localized in sequence 1182-1191, is
      the core of the immunodominant and highly uveitogenic determinant of IRBP. The
      second site localizes within sequence 1183-1191 and becomes detectable only when
      tryptophan at position 1182 is deleted. Lymphocytes sensitized against the first,
      larger site recognized all longer peptides within sequence 1169-1191, as well as
      whole IRBP. In contrast, lymphocytes sensitized against the second, short epitope
      recognized only two peptides, 1184-1191 and (to a lesser degree) 1183-1191. The
      responses to both sites were restricted by the same major histocompatibility
      complex (MHC) product (I-A), as shown by monoclonal antibody blocking and by the
      finding that the lymphocyte response to 1184-1191 was competitively inhibited by
      peptide 1181-1191. The unique finding of two completely distinct antigenic sites
      within a decapeptide could be explained by the hypothesis that peptides of the
      two sites combine with the MHC molecule on antigen-presenting cells by different
      configurations, thus forming two distinct antigenicities.

PMID- 1371241
TI  - CD3.TCR1, a human CD3 epitope expressed on viable gamma/delta lymphocytes
      exclusively.
AB  - T lymphocytes express either the alpha/beta or the gamma/delta receptor (TCR) in
      a mutually exclusive fashion. Both structures are associated on the cell membrane
      with the CD3 proteins which are thought to transduce signals resulting from
      antigen recognition. The CD3 complex is present in both alpha/beta and
      gamma/delta cells and includes at least five proteins (designated gamma, delta,
      epsilon, zeta and eta). We have developed here a novel mAb, anti-CD3.TCR1, which
      immunoprecipitates the CD3 molecules from both alpha/beta and gamma/delta cells
      lysates following solubilization with Triton X-100. While the SDS-PAGE migration
      profile of the material recognized by either anti-CD3.TCR1 or anti-OKT3 are
      superimposable in both cell types, this mAb recognizes viable untreated
      gamma/delta T lymphocytes exclusively. These findings further support the view
      that molecular interactions within the TCR/CD3 protein complex are distinct in
      the two T lymphocyte populations.

PMID- 1371242
TI  - DNA fragmentation and cell death is selectively triggered in activated human
      lymphocytes by Fas antigen engagement.
AB  - Fas is a mouse monoclonal antibody-defined cell surface antigen of an unknown
      physiologic function. Previous studies demonstrated that the anti-Fas antibody
      mediated apoptosis in those cells sensitive to tumor necrosis factor (TNF) and,
      further, triggered the co-downregulation of tumor necrosis factor receptors (TNF
      Rs). These findings led to speculation that Fas may be associated with TNF-Rs.
      The present studies were undertaken as an extension of our previous work on the
      obligate requirement for TNF in development and maintenance of cytotoxic
      lymphocytes and were designed to analyze the expression and consequences of Fas
      engagement in these cells. Herein, we demonstrate that, in contrast to TNF-R
      expression, both resting and IL-2-activated lymphocytes express Fas. In
      accordance with previous studies using tumor cell lines, lymphocytes rapidly
      downregulate TNF-Rs after treatment with anti-Fas. The ability of anti-Fas to
      mediate apoptotic cell death in lymphocytes, however, was dependent upon the
      status of cellular activation. For example, lymphocytes activated in IL-2 for
      longer than 4 days underwent rapid DNA fragmentation and cell death after anti
      Fas treatment. Despite their expression of Fas, nonactivated lymphocytes and
      those activated for periods less than 4 days were refractory to antibody-mediated
      cell killing. Because anti-Fas-mediated lethality is selective for chronically
      activated lymphocytes, Fas may prove to be an appropriate target for
      immunosuppressive intervention.

PMID- 1371243
TI  - Unusually diverse T cell response to a repeating tripeptide epitope.
AB  - The immune system utilizes a diverse T cell repertoire for the recognition of
      foreign antigens in the context of self MHC gene products. We have examined the
      potential diversity of the T cell response directed to a immunodominant repeating
      tripeptide epitope (EYA)5. This peptide represents one of the two T cell epitopes
      on the synthetic alpha-helical polypeptide antigen Poly 18, Poly EYK(EYA)5 in H
      2d mice and does not require antigen processing prior to presentation to Poly 18
      specific T cell hybridomas. The T cell response directed to the repeating
      tripeptide epitope (EYA)5 is extremely heterogenous even though the epitope has a
      relatively simple amino acid sequence. We have analyzed the fine specificity of
      21 randomly chosen Poly 18-reactive, (EYA)5-specific and H-2d-restricted T cell
      hybridomas derived from H-2d, H-2bxd, and H-2b----H-2bxd Poly 18-responding mice
      to determine the number of unique antigen reactivity patterns represented by this
      T cell population. We used alanine- and/or lysine-substituted (EYA)5 peptides and
      a panel of haplotype-varied splenocytes and observed a great deal of
      microheterogeneity in response. We find that 13 of the 21 hybridomas have a
      distinct fine antigen specificity and T cell receptors. The binding of (EYA)5 to
      the antigen-binding groove of I-Ad appears to generate a highly diversified T
      cell response. Therefore, (EYA)5-I-Ad complex allows the activation of unrelated
      T cell clonotypes with the same overall antigen specificity and MHC restriction,
      but with distinct microheterogeneity in response and receptor usage.

PMID- 1371244
TI  - Subset-specific co-stimulatory signals are required for IL-2 production but not
      growth inhibition responses by T cell hybrids specific for myelin basic protein.
AB  - Two distinct types of T cell hybridomas (designated THYB-1 and T-HYB-2) were
      derived by fusing BW5147 thymoma cells with encephalitogenic T helper cells from
      Lewis rats. Both subsets required MHC-restricted presentation of determinants
      within the 72-86 peptide sequence of myelin basic protein (MBP) as a requisite
      signal for IL-2 production. Unlike THYB-1 hybrids, however, THYB-2 hybrids
      required additional accessory cell activities that were mediated by
      radiosensitive nonadherent (RS-NAdh) splenocytes (SPL). In this study, we
      describe two observations indicating that RS-NAdh SPL enable MBP-specific
      responses of THYB-2 hybrids by providing subset-specific co-stimulatory signals
      that act independently of antigen recognition pathways. First, RS-NAdh SPL were
      required by THYB-2 hybrids for MBP-stimulated IL-2 production but were not needed
      when MBP-specific inhibition of hybrid growth was used as an alternative measure
      of cellular activation. Second, PMA and ionomycin induced optimal IL-2 production
      by both THYB-1 hybrids and BW5147 thymoma cells but only stimulated low or
      marginal levels of IL-2 production by THYB-2 hybrids. Together, these
      observations indicate that RS-NAdh SPL were required for the specific response of
      IL-2 production regardless of whether the response was stimulated by antigen or
      by mitogens that bypass initial antigen recognition events. This study thereby
      provides additional evidence that distinct stimulus-response relationships define
      two T-helper cell lineages in experimental autoimmune encephalomyelitis.

PMID- 1371245
TI  - Isolation and characterization of cDNA and genomic sequences for mouse O6
      methylguanine-DNA methyltransferase.
AB  - An enzyme, O6-methylguanine-DNA methyltransferase, is present in various
      organisms and plays an important role in repair of DNA damaged by alkylating
      agents. The enzyme transfers methyl groups from O6-methylguanine and other
      methylated moieties of the DNA to its own molecule. As a first step to construct
      animal models with altered levels of the enzyme activity, we cloned cDNA and
      genomic DNA sequences for mouse methyltransferase and elucidated their
      structures. The nucleotide sequence of the cDNA revealed an open reading frame
      comprising 211 amino acid residues. The mol. wt of mouse O6-methylguanine-DNA
      methyltransferase, calculated from the predicted amino acid sequence, was 22,400,
      and the methyltransferase protein of this size was present when the cDNA was
      expressed in methyltransferase-deficient human cells. The predicted amino acid
      sequence of the mouse methyltransferase exhibits an intense homology with those
      of human and bacterial counterparts. Using the cDNA as a probe, part of the mouse
      gene for methyltransferase was isolated. The gene consisted of at least four
      exons and spanned greater than 145 kb. Sequences around the exon/intron junctions
      for the mouse gene are almost the same as those for the human species.

PMID- 1371246
TI  - Respiratory alterations due to urban air pollution: an experimental study in
      rats.
AB  - In order to assess the adverse effects of urban levels of air pollution, rats
      were used as biological indicators in a chronic exposure experiment. Animals were
      housed for 6 months in the center of Sao Paulo (the largest South American city)
      and were compared to controls kept for the same period in a clean area. Pollution
      levels were obtained from a State air pollution monitoring station, 200 m distant
      from the exposure place, which provided the levels of CO, SO2, particulates, and
      ozone. The animals were submitted to several tests focusing on the respiratory
      system, comprising pulmonary function tests, studies on mucociliary clearance and
      mucus rheology, histochemical evaluation of airways, bronchoalveolar lavage, and
      ultrastructural studies of the epithelium of the airways. Rats exposed to air
      pollution developed secretory cell hyperplasia in the airways, ultrastructural
      ciliary alterations, and a more rigid mucus, changes that caused mucociliary
      clearance impairment. In addition, nasal resistance and the number of
      inflammatory cells recovered by bronchoalveolar lavage were increased in air
      pollution exposed animals. The results obtained in the present investigation
      suggest that chronic exposure to urban levels of air pollution may cause
      respiratory lesions in rats.

PMID- 1371247
TI  - Transcriptional control in hepatocytes of normal and c14CoS albino deletion mice.
AB  - The transcription rates of the albumin and alpha-fetoprotein (alpha FP) genes
      were reduced to marginally detectable levels in livers of newborn or fetal c14CoS
      albino deletion mutant mice, which lack the hepatocyte specific developmental
      regulation (hsdr-1) locus on chromosome 7 and die shortly after birth. However,
      steady-state levels of these two mRNAs in livers of mutant mice were similar to
      those in normal mice, where these genes are actively transcribed. In c14CoS mice,
      transcription rates of transcription factor genes HNF-1, C/EBP and HNF-4 were
      reduced, albeit to different extents. These effects are specific because
      transcription of the HNF-3, DBP, LAP and Jun-B genes remained normal in mutant
      mice. Steady-state levels of all of these mRNAs reflected the transcriptional
      activities. Levels of HNF-1 and HNF-4 mRNAs showed much greater depression than
      that of C/EBP in mutant liver. The availability of this group of transcription
      factors may be reduced in c14CoS hepatocytes and therefore caused depressed
      transcription rates of their target genes such as those encoding albumin and
      alpha FP. However, the normal steady-state levels of albumin and alpha FP mRNAs
      in mutant mice remains unexplained. Fetal c14CoS hepatocytes in primary culture
      did acquire competence for glucocorticoid inducible transcription of the albumin,
      alpha FP, HNF-4 and metallothionein genes but not of the tyrosine
      aminotransferase (TAT) gene. These results indicate that the hsdr-1 locus is
      dispensable for the glucocorticoid induced transcription of these genes but not
      of TAT. The effects caused by the c14CoS deletion are pleiotropic in controlling
      the expression of numerous genes at distinct levels in the liver.

PMID- 1371248
TI  - Critical role of a common transcription factor, IRF-1, in the regulation of IFN
      beta and IFN-inducible genes.
AB  - Interferon regulatory factor 1 (IRF-1) is a protein that binds to cis-elements
      within the promoter of interferon (IFN)-beta and some IFN-inducible genes. We
      used a human fibroblast line, GM-637, to generate stable transfectants
      constitutively expressing IRF-1 mRNA in either the sense or antisense
      orientation. Upon induction with poly-(I).poly(C) or Newcastle disease virus,
      cells expressing sense IRF-1 mRNA produced significantly higher levels of IFN
      beta mRNA and protein than control cells, whereas cells expressing antisense IRF
      1 mRNA produced little or no IFN-beta mRNA and protein. Furthermore, clear
      differences were seen among the transfectants in the level of expression of two
      IFN-induced genes (2'-5'-oligoadenylate synthetase and class I HLA). Our data
      show that IRF-1 is essential for the induced expression of the IFN-beta gene. The
      results also indicate an important role of IRF-1 in the expression of IFN
      inducible genes and suggest a role for IRF-1 in many other cytokine actions.

PMID- 1371251
TI  - Cystic fibrosis transmembrane conductance regulator (CFTR) gene transcripts.

PMID- 1371249
TI  - Conformation of B-DNA containing O6-ethyl-G-C base pairs stabilized by minor
      groove binding drugs: molecular structure of d(CGC[e6G]AATTCGCG complexed with
      Hoechst 33258 or Hoechst 33342.
AB  - O6-ethyl-G (e6G) is an important DNA lesion, caused by the exposure of cells to
      alkylating agents such as N-ethyl-N-nitrosourea. A strong correlation exists
      between persistence of e6G lesion and subsequent carcinogenic conversion. We have
      determined the three-dimensional structure of a DNA molecule incorporating the
      e6G lesion by X-ray crystallography. The DNA dodecamer d(CGC[e6G]AATTCGCG),
      complexed to minor groove binding drugs Hoechst 33258 or Hoechst 33342, has been
      crystallized in the space group P212121, isomorphous to other related dodecamer
      DNA crystals. In addition, the native dodecamer d(CGCGAATTCGCG) was crystallized
      with Hoechst 33342. All three new structures were solved by the molecular
      replacement method and refined by the constrained least squares procedure to R
      factors of approximately 16% at approximately 2.0 A resolution. In the structure
      of three Hoechst drug-dodecamer complexes in addition to the one published
      earlier [Teng et al. (1988) Nucleic Acids Res., 16, 2671-2690], the Hoechst
      molecule lies squarely at the central AATT site with the ends approaching the G4
      C21 and the G16-C9 base pairs, consistent with other spectroscopic data, but not
      with another crystal structure reported [Pjura et al. (1987) J. Mol. Biol., 197,
      257-271]. The two independent e6G-C base pairs in the DNA duplex adopt different
      base pairing schemes. The e6G4-C21 base pair has a configuration similar to a
      normal Watson-Crick base pair, except with bifurcated hydrogen bonds between e6G4
      and C21, and the ethyl group is in the proximal orientation. In contrast, the
      e6G16-C9 base pair adopts a wobble configuration and the ethyl group is in the
      distal orientation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371250
TI  - CpG methylated minichromosomes become inaccessible for V(D)J recombination after
      undergoing replication.
AB  - The physical parameters controlling the accessibility of antigen receptor loci to
      the V(D)J recombination activity are unknown. We have used minichromosome
      substrates to study the role that CpG methylation might play in controlling V(D)J
      recombination site accessibility. We find that CpG methylation decreases the
      V(D)J recombination of these substrates more than 100-fold. The decrease
      correlates with a considerable increase in resistance to endonuclease digestion
      of the methylated minichromosome DNA. The minichromosomes acquire resistance to
      both the intracellular V(D)J recombinase and exogenous endonuclease only after
      DNA replication. Therefore, CpG methylation specifies a chromatin structure that,
      upon DNA replication, is resistant to eukaryotic site-specific recombination.
      These findings are important to V(D)J recombination as well as to the chromatin
      assembly of methylated DNA during replication.

PMID- 1371252
TI  - Monoclonal antibodies to human pancreatic trypsin 1 inhibit the activation of
      human trypsinogens 1 and 2.
AB  - Two monoclonal antibodies (Mab) raised against human pancreatic trypsin 1, Mab G6
      and A8, were previously isolated and characterized. The two Mab which recognize
      trypsinogen 1 are found to inhibit the activation of trypsinogen 1 by
      enterokinase. The inhibition of activation by the two Mab is concentration
      dependent, rapid and virtually complete with Mab G6. Activation of trypsinogen 2
      is totally inhibited by Mab G6, while Mab A8 has no effect on the activation of
      trypsinogen 2. The two monoclonal antibodies have opposite effects on the
      proteolytic activity of trypsin 1; Mab G6 increases proteolytic activity while
      Mab A8 inhibits trypsin activity by as much as 40%. This inhibition is
      concentration dependent but cannot account for the complete inhibition of
      activation of trypsinogen 1. Neither monoclonal antibody significantly inhibits
      the esterolytic activity of either form of human trypsin. Western-blot analysis
      of the reactivity of the two monoclonal antibodies with trypsinogens of various
      species shows that only Mab G6 cross-reacts with dog trypsinogen.

PMID- 1371253
TI  - Amino acid sequence and immunological characterization with monoclonal antibodies
      of two toxins from the venom of the scorpion Centruroides noxius Hoffmann.
AB  - Two toxins, which we propose to call toxins 2 and 3, were purified to homogeneity
      from the venom of the scorpion Centruroides noxius Hoffmann. The full primary
      structures of both peptides (66 amino acid residues each) was determined.
      Sequence comparison indicates that the two new toxins display 79% identity and
      present a high similarity to previously characterized Centruroides toxins, the
      most similar toxins being Centruroides suffusus toxin 2 and Centruroides limpidus
      tecomanus toxin 1. Six monoclonal antibodies (mAb) directed against purified
      fraction II-9.2 (which contains toxins 2 and 3) were isolated in order to carry
      out the immunochemical characterization of these toxins. mAb BCF2, BCF3, BCF7 and
      BCF9 reacted only with toxin 2, whereas BCF1 and BCF8 reacted with both toxins 2
      and 3 with the same affinity. Simultaneous binding of mAb pairs to the toxin and
      cross-reactivity of the venoms of different scorpions with the mAb were examined.
      The results of these experiments showed that the mAb define four different
      epitopes (A-D). Epitope A (BCF8) is topographically unrelated to epitopes B (BCF2
      and BCF7), C (BCF3) and D (BCF9) but the latter three appear to be more closely
      related or in close proximity to each other. Epitope A was found in all
      Centruroides venoms tested as well as on four different purified toxins of C.
      noxius, and thus seems to correspond to a highly conserved structure. Based on
      the cross-reactivity of their venoms with the mAb, Centruroides species could be
      classified in the following order: Centruroides elegans, Centruroides suffusus
      suffusus = Centruroides infamatus infamatus, Centruroides limpidus tecomanus,
      Centruroides limpidus limpidus, and Centruroides limpidus acatlanensis, according
      to increasing immunochemical relatedness of their toxins to those of Centruroides
      noxius. All six mAb inhibited the binding of toxin 2 to rat brain synaptosomal
      membranes, but only mAb BCF2, which belongs to the IgG2a subclass, displayed a
      clear neutralizing activity in vivo.

PMID- 1371254
TI  - Electron-proton coupling in cytochrome c studied using protein variants.
AB  - An NMR study of the cytochrome c variant Asn52Ile is used to show how the redox
      state change in native cytochrome c is coupled to a rearrangement of a proton
      network which runs through the cytochrome c molecule. The substitution breaks the
      H-bond network and removes the coupling. The uncovering of this putative proton
      channel and the connection of changes to it with redox state changes of the iron
      centre of the protein allows a possible description of the way in which redox
      energy state changes can be coupled to energization and gating of protons in
      membranes.

PMID- 1371255
TI  - Characterization of the upp gene encoding uracil phosphoribosyltransferase of
      Escherichia coli K12.
AB  - The upp gene coding for uracil phosphoribosyltransferase was subcloned on a 5-kb
      EcoRI restriction fragment along with the purMN operon. By a combination of
      complementation, deletion and minicell analyses, the upp gene was located
      adjacent to and divergently transcribed from the purMN operon. All three gene
      products could be identified in minicell extracts. The cloned upp gene shows an
      elevated expression upon uracil starvation. The nucleotide sequence and
      transcription start of the gene were determined. The sequence yields an open
      reading frame of 624 nucleotides encoding a protein of 22.5 kDa which is in
      agreement with the previously determined subunit Mr of the purified enzyme. A
      putative 5-phosphoribosyl-alpha-1-diphosphate (PRPP) binding site has been
      identified which is similar to the PRPP binding site of the yeast uracil
      phosphoribosyltransferase.

PMID- 1371256
TI  - The embryo pancreas is a source of increased yolk amylase in the fertilized eggs
      of domestic fowls.
AB  - The amylases were studied in the yolk of fertilized eggs and in the pancreases of
      the embryos of domestic fowls. The amylase activity in the yolk increased
      markedly from 13 days of incubation until hatching, but the activity decreased
      when the embryos were taken out of the eggs. The isoamylases in the yolk and in
      the pancreas of the embryo were identical electrophoretically. The amylase occurs
      mainly in the pancreas of the embryo. We think that the increase in amylase
      activity in the yolk of fertilized eggs during incubation depends upon the
      accumulation of pancreatic amylase synthesized by the developing embryo in the
      egg.

PMID- 1371257
TI  - Babesia bovis: bovine helper T cell lines reactive with soluble and membrane
      antigens of merozoites.
AB  - Babesia bovis-specific T cell lines were established from cattle infected with
      either tick-derived or cultured parasites by stimulation of peripheral blood
      mononuclear cells with a crude parasite membrane fraction. Induction and
      enrichment of CD4+ T cells occurred over time. All cell lines responded
      vigorously and in a dose-dependent, MHC-restricted manner to intact merozoites,
      and to soluble and membrane fractions derived from merozoites by homogenization
      and high-speed centrifugation. Solubilization of the membrane fraction with
      nondenaturing zwitterionic or nonionic detergents yielded antigenic extracts
      which also stimulated the T cells. However, a differential response was observed,
      in that cell lines from one animal proliferated vigorously to the detergent
      extracts of the membrane fraction, whereas cell lines from a second animal
      proliferated only weakly to these extracts. SDS-PAGE analysis revealed common
      protein bands of 90 and 22 kDa in the various immunogenic fractions. Cell lines
      from the animal infected with cultured parasites also responded to parasite
      culture supernatant "exoantigens" and to the related parasite, Babesia bigemina.
      We conclude that antigens present in merozoite membranes and soluble parasite
      extracts preferentially stimulate CD4+ T cells from cattle immune to Babesia
      bovis. The differential pattern of response of T cell lines from different cattle
      suggests that more than one protein or epitope is immunodominant for T cells.

PMID- 1371258
TI  - Expression of interleukin-1 (IL-1) beta messenger ribonucleic acid (mRNA) and IL
      1 receptor antagonist mRNA in peritoneal macrophages from patients with
      endometriosis.
AB  - OBJECTIVE: To investigate the expression of interleukin-1 (IL-1) beta messenger
      ribonucleic acid (mRNA) and IL-1 receptor antagonist (IL-1ra) mRNA in peritoneal
      macrophages. DESIGN, SETTING: Peritoneal fluid (PF) samples were collected from
      patients who underwent laparoscopy or laparotomy. Northern blot analysis was
      performed at the reproductive research laboratory. PATIENTS: Twenty-six patients
      with endometriosis, 10 patients with postinflammatory pelvic adhesion, and 12
      control women with normal pelvis. MAIN OUTCOME MEASURE: Polyadenylated RNA
      isolated from peritoneal macrophages was analyzed on Northern blots by using
      synthetic oligonucleotide probes. RESULTS: The level of IL-1 beta mRNA expression
      was elevated in the group with stage I endometriosis, whereas the increased
      expression of IL-1ra mRNA was observed in the group with stages III and IV
      endometriosis. The level of IL-1 beta mRNA showed a positive correlation with
      that of IL-1 beta in PF and a negative correlation with the level of IL-1ra mRNA.
      CONCLUSIONS: Our results suggest that peritoneal macrophages express IL-1ra mRNA
      rather than IL-1 beta mRNA with the progress of endometriosis and that peritoneal
      macrophages may secrete IL-1ra protein that modulates the effects of IL-1.

PMID- 1371259
TI  - The relationship between alterations in spermatozoal deoxyribonucleic acid,
      heparin binding sites, and semen quality.
AB  - OBJECTIVE: To assess the relationship between spermatozoal deoxyribonucleic acid
      (DNA) and fertilizing potential. DESIGN: Semen samples were examined from nine
      fertile donors and six donors without a confirmed pregnancy. All samples were in
      the normal range for count, morphology, and motility. Spermatozoa from these
      specimens were stained with acridine orange or Feulgen's reagent. The presence of
      heparin binding sites was determined by counting the number of spermatozoa that
      bound to heparin-coated agarose beads. RESULTS: Acridine orange staining
      demonstrated that in the fertile group 42% +/- 2% of the spermatozoa fluoresced
      green indicating that the DNA was intact, whereas only 25% +/- 3% of the
      spermatozoa fluoresced green in the nonfertile group (P less than 0.05).
      Feulgen's staining revealed that more spermatozoa from infertile donors showed a
      heterogeneous DNA distribution (P less than 0.05). The DNA content of spermatozoa
      with heterogeneous distribution of DNA was reduced by 10% compared with those
      with homogeneous DNA (P less than 0.05). Normal spermatozoa as well as those with
      DNA anomalies possessed heparin binding sites. CONCLUSIONS: These data
      demonstrated that in donor specimens with normal counts, morphology, and
      motility, a higher percentage of spermatozoa possess less and/or denatured DNA in
      the infertile group compared with the fertile donors. In contrast, the surface
      membranes of spermatozoa with altered DNA have heparin binding sites as do
      spermatozoa with intact DNA.

PMID- 1371260
TI  - Angiogenesis in the female reproductive system.
AB  - In adult tissues, capillary growth (angiogenesis) occurs normally during tissue
      repair, such as in healing of wounds and fractures. Rampant capillary growth is
      associated with various pathological conditions, including tumor growth,
      retinopathies, hemangiomas, fibroses and rheumatoid arthritis. The female
      reproductive organs (i.e., ovary, uterus, and placenta) exhibit dynamic, periodic
      growth and regression accompanied by equally dramatic changes in rates of blood
      flow. It is not surprising, therefore, that they are some of the few adult
      tissues in which angiogenesis occurs as a normal process. Thus, the female
      reproductive system provides a unique model for studying regulation of
      angiogenesis during growth and differentiation of normal adult tissues. Ovarian,
      uterine, and placental tissues recently have been shown to contain and produce
      angiogenic and anti-angiogenic factors. This review discusses the current state
      of knowledge regarding angiogenic processes and their regulation in female
      reproductive tissues. In addition, implications of this research for regulation
      of fertility as well as for control of angiogenesis in other normal and
      pathological processes are discussed.

PMID- 1371261
TI  - Whipple's disease complicated by a retinal Jarisch-Herxheimer reaction: a case
      report.
AB  - A 36 year old white man was diagnosed as having Whipple's disease after a
      prolonged illness of lethargy, night sweats, and weight loss associated with
      lymphadenopathy and splenomegaly. Biopsy specimen of an inguinal lymph node
      confirmed the presence of periodic acid Schiff positive macrophages and culture
      gave a pure growth of Corynebacterium jeikeium. Twelve hours after the
      introduction of oral co-trimoxazole and streptomycin the patient's condition
      deteriorated. He became confused, feverish, and developed florid retinal
      vasculitis with associated visual impairment. Both the systemic symptoms and the
      retinal vasculitis responded to treatment with corticosteroids and his vision
      returned to normal. We think this was a Jarisch-Herxheimer reaction not
      previously described in Whipple's disease and advise inspection of the fundi of
      such patients before starting treatment.

PMID- 1371262
TI  - Cytokeratin expression in adrenocortical neoplasia: an immunohistochemical and
      biochemical study with implications for the differential diagnosis of
      adrenocortical, hepatocellular, and renal cell carcinoma.
AB  - The immunostaining patterns of adrenocortical tumors are not clearly defined,
      primarily due to their inconsistent expression of cytokeratins (CK). To address
      this issue and to investigate whether adrenocortical tumors can be
      immunohistochemically differentiated from histologically similar tumors arising
      from the kidney and liver, we studied four normal adrenal glands, two
      adrenocortical adenomas (ACAs), 31 adrenocortical carcinomas (ACCs), 37 renal
      cell carcinomas (RCCs), and 33 hepatocellular carcinomas (HCCs) with anti-CK
      antibodies AE1, CAM 5.2, UCD/PR10.11, 35BH11, PKK1, and Ks19.1, as well as
      antibodies to vimentin (VIM), epithelial membrane antigen (EMA), and HMFG-2.
      Normal adrenal cortical cells showed variable staining with all anti-CK
      antibodies on fixed and frozen sections. In contrast, only one of two fixed ACAs
      stained with a single anti-CK, although both neoplasms reacted with multiple anti
      CK antibodies on frozen sections. Similarly, 20 of 31 fixed ACCs contained VIM,
      but only one tumor stained for CK; frozen sections of this and another,
      previously negative tumor, however, stained with most of the anti-CK antibodies
      tested. One-dimensional Western immunoblot analysis confirmed the presence of CKs
      18 and 19 in two examples of normal adrenal cortex, one ACA, and the ACC
      immunohistochemically positive on fixed and frozen sections, with CK 19
      identified in the ACC that was positive on frozen section alone. All fixed HCCs
      and most RCCs stained with multiple anti-CK antibodies (33 and 34 cases,
      respectively), with a proportion of tumors positive for VIM (six and 22 cases,
      respectively), EMA (seven and 30 cases, respectively), and HMFG-2 (15 and 28
      cases, respectively). The results suggest that CK expression is diminished in
      most adrenocortical tumors to levels too low to be recognized following the
      deleterious effects of fixation. While the immunohistochemical absence of CK,
      EMA, and HMFG-2 in fixed sections in the majority of ACCs is distinctive,
      sufficient phenotypic overlap exists such that differentiation between RCC and
      HCC may not be possible in an individual case.

PMID- 1371264
TI  - Carrier detection and prenatal diagnosis of cystic fibrosis using an intragenic
      TA-repeat polymorphism.
AB  - We have analysed the segregation of a TA-repeat polymorphism in intron 17b of the
      cystic fibrosis transmembrane conductance regulator gene responsible for cystic
      fibrosis (CF) in 23 French CF families non-informative for the delta F508
      mutation (i.e. with at least one parent not carrying delta F508) or closely
      linked DNA markers. At least 13 different alleles ranging from 7 to 45 repeats
      were observed and the detected heterozygosity was 89%. Of the 23 families
      studied, 19 were fully informative for prenatal diagnosis or carrier detection, 3
      were partially informative and one was not informative. In 6 families, prenatal
      diagnosis for CF or carrier detection in siblings of CF cases were performed
      using this polymorphism.

PMID- 1371265
TI  - A nonsense mutation (R1158X) and a splicing mutation (3849 + 4A----G) in exon 19
      of the cystic fibrosis transmembrane conductance regulator gene.

PMID- 1371263
TI  - Intra- and extragenic marker haplotypes of CFTR mutations in cystic fibrosis
      families.
AB  - In order to facilitate the screening for the less common mutations in the cystic
      fibrosis (CF) gene viz., the CF transmembrane conductance regulator gene (CFTR),
      marker haplotypes were determined for German non-CF (N) and CF chromosomes by
      polymerase chain reaction analysis of four polymorphisms upstream of the CF gene
      (XV-2c, KM.19, MP6-D9, J44) and six intragenic polymorphisms (GATT, TUB9, M470V,
      T854T, TUB18, TUB20) that span the CFTR gene from exon 6 through exon 21. Novel
      informative sequence variants of CFTR were detected in front of exons 10 (1525-61
      A or G), 19 (3601-65 C or A), and 21 (4006-200 A or G). The CF locus exhibits
      strong long-range marker-marker linkage disequilibrium with breakpoints of
      recombination between XV-2c and KM.19, and between exons 10 and 19 of CFTR.
      Marker alleles of GATT-TUB9 and TUB18-TUB20 were found to be in absolute linkage
      disequilibrium. Four major haplotypes encompass more than 90% of German N and CF
      chromosomes. Fifteen CFTR mutations detected on 421 out of 500 CF chromosomes
      were each identified on one of these four predominant 7-marker haplotypes.
      Whereas all analysed delta F508 chromosomes carried the same KM.19-D9-J44-GATT
      TUB9-M470V-T854T haplotype, another frequent mutation in Germany, R553X, was
      identified on two different major haplotypes. Hence, a priori haplotyping cannot
      exclude a particular CF mutation, but in combination with population genetic
      data, enables mutations to be ranked by decreasing probability.

PMID- 1371266
TI  - Evaluation of monoclonal antibodies having specificity for human IgG subclasses:
      results of the 2nd IUIS/WHO collaborative study.
AB  - Following the 1st IUIS/WHO Collaborative Study of monoclonal anti-IgG subclass
      antibodies, a panel of WHO Specificity Reference Reagents (SRR) was established
      [Jefferis, R., et al. (1985) Immunol. Lett., 10, 223]. At the time, the hope was
      expressed that further reagents particularly for IgG2, and other allotypic
      specificities would become available which could be applied in a wide range of
      assay protocols. The 2nd study reports the evaluation of nineteen anti-subclass
      and seven anti-allotype monoclonal antibodies. The anti-IgG1 antibody HP6187 was
      equivalent in performance to the SRR. Others, that were not of the mouse IgG1
      isotype, may be useful for particular applications. The anti-IgG2 antibody HP6200
      could be a valuable addition to the WHO SRR; it is specific for an epitope in the
      Fab region but does not have the light chain bias of HP6014. Antibodies of
      putative allotype specificity exhibited the claimed specificity when used within
      protocols similar to those employed by the originating laboratory. It appears to
      be inherent in the nature of the epitopes (allotopes) recognized that it will
      take several years before reagents applicable to a wide range of techniques will
      become available.

PMID- 1371267
TI  - Development of a Langerhans cell phenotype from peripheral blood monocytes.
AB  - Epidermal Langerhans cells (ELC) are definitively primed to differentiate into
      dendritic cells (DC). It is unknown at what stage of monocyte development this
      priming occurs. In a culture system characterized by low paracrine stimulation,
      i.e. Iscove's modified Dulbecco medium (IMDM) with 2% FCS, we tested the ability
      of peripheral blood monocytes to turn to the route of the LC-DC lineage. In this
      system monocytes did not develop significant yeast cell phagocytosis, although
      mannose receptors were available. However, they became strong stimulators of
      mannan specific T cell proliferation. Phenotype development was analysed by flow
      cytometry using the monoclonal antibodies OKT6 (CD1a), IOT2 (HLA-DR), IOM2 (CD14)
      and the ligand Man-BSA-FITC. CD1a was the first marker which distinguished
      cultured monocytes from developing macrophages, obtained by addition of 8% human
      serum. Like cord blood Langerhans cells (CBLC) they internalized OKT6 in deep
      coated pits. They maintained a phenotype of monocyte derived Langerhans cells
      (MoLC) during eight days of in vitro culture, expressing CD1a, mannose receptors
      and HLA-DR and decreasing CD14, if left in their own conditioned medium. MoLC
      could be converted into macrophages by addition of human serum only within the
      first four days in vitro. Our data suggest that monocytes acquire an LC phenotype
      by autocrine stimulation.

PMID- 1371268
TI  - Identification and localization of a limited number of predominant conformation
      independent antibody epitopes of Theiler's murine encephalomyelitus virus.
AB  - Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in
      mice is a well established animal model for human multiple sclerosis (MS).
      Identification of pathogenic epitopes may be helpful in understanding the
      pathogenesis of this immune-mediated disease. In order to analyze the viral
      epitopes, we have generated approx. 150 recombinant lambda gt11 clones expressing
      various capsid areas of TMEV. Six predominant areas, ranging from 13-26 amino
      acid residues, (3 in VP1, 2 in VP2 and 1 in VP3) are readily recognized by
      conformation-independent antibodies from virus-infected mice. These areas have
      been designated as A-1A (VP1 13-27th residues), A-1B (VP1 145-167), A-1C (VP1 251
      276), A-2A (VP2 2-14), A-2B (VP2 165-179), and A-3A (tentatively VP3 24-43).
      Antibodies from TMEV-infected susceptible SJL/J mice strongly react with A-1B, A
      2A and A-2B, in contrast to antibodies from resistant BALB/c mice which mainly
      recognize A-1A and A-2A. Interestingly, the reactivity pattern of antibodies from
      TMEV-infected mice are somewhat different from that of antibodies from TMEV
      immunized mice. Although the majority of antibodies in TMEV-infected mice
      recognizes conformation-dependent epitopes, the differential recognition of the
      conformation-independent antibody epitopes by susceptible mice may play a role in
      TMEV-induced demyelination.

PMID- 1371269
TI  - Herpes simplex viral infection of the mouse trigeminal ganglion.
      Immunohistochemical analysis of cell populations.
AB  - Several distinct populations of sensory neurons in the ophthalmic region of the
      mouse trigeminal ganglion have been identified by their reactivity to antibodies
      raised against substance P (SP), calcitonin gene-related peptide (CGRP), cell
      surface glycoconjugates SSEA3 and LD2, and the plant lectin, Bandeiraea
      simplicifolia lectin 1, isolectin 4 (BSIL4). Thirty-six percent of the neurons in
      the ophthalmic portion of the mouse trigeminal ganglion express CGRP and 17%, SP.
      All neurons that express SP also express CGRP. Forty percent of the neurons in
      the ophthalmic region of the ganglion are recognized by monoclonal antisera to
      SSEA3, and 66% of this population also express the neuropeptides SP or CGRP. The
      neuronal population recognized by BSIL4 is identical to the population with the
      LD2 epitope. This population of cells (BSIL4/LD2) does not express the SSEA3
      glycoconjugate and is largely nonpeptidergic. All four populations of sensory
      neurons (SP, CGRP, SSEA3, and LD2/BSIL4) can be infected by herpes simplex virus
      (HSV). However, the relative proportion of SSEA3- and LD2/BSIL4-labeled cells
      that were infected productively with HSV was much less than expected based on the
      relative size of the populations of these neurons in the ophthalmic region of the
      ganglion.

PMID- 1371270
TI  - Aerosol infection of rhesus macaques with Junin virus.
AB  - The purpose of our work was to determine if aerosols of Junin virus can infect
      rhesus macaques and if the disease is the same as that produced by virus
      inoculated parenterally. The 6 macaques exposed to the virus by aerosol became
      acutely ill during the 3rd week after exposure, and all died. Three died by day
      21, while the remainder died after 1 month. Junin virus was found primarily in
      visceral organs of those animals dying before 21 days after infection and in the
      central nervous system tissues from animals dying later. Histological changes
      were similar to those reported in rhesus monkeys after parenteral Junin viral
      infection. Gastrointestinal necrosis, however, was less severe in aerosol
      infected animals and the associated septicemia was not seen. High levels of alpha
      interferon were detected by the 3rd day in all infected macaques. Experimental
      Argentine hemorrhagic fever induced by aerosol infection in rhesus macaques was
      similar to that seen after parenteral challenge and mimicked closely the clinical
      syndrome observed in humans.

PMID- 1371271
TI  - Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human
      matrix metalloproteinase 9.
AB  - Matrix metalloproteinase 9 (MMP-9), also known as 92-kDa gelatinase/type IV
      collagenase, is secreted from neutrophils, macrophages, and a number of
      transformed cells in zymogen form. Here we report that matrix metalloproteinase 3
      (MMP-3/stromelysin) is an activator of the precursor of matrix metalloproteinase
      9 (proMMP-9). MMP-3 initially cleaves proMMP-9 at the Glu40-Met41 bond located in
      the middle of the propeptide to generate an 86-kDa intermediate. Cleavage of this
      bond triggers a change in proMMP-9 that renders the Arg87-Phe88 bond susceptible
      to the second cleavage by MMP-3, resulting in conversion to an 82-kDa form. alpha
      2-Macroglobulin binding studies of partially activated MMP-9 demonstrate that the
      82-kDa species is proteolytically active, but not the initial intermediate of 86
      kDa. This stepwise activation mechanism of proMMP-9 is analogous to those of
      other members of the MMP family, but the action of MMP-3 on proMMP-9 is the first
      example of zymogen activation that can be triggered by another member of the MMP
      family. The results imply that MMP-3 may be an effective activator of proMMP-9 in
      vivo.

PMID- 1371272
TI  - The effects of dNTP pool imbalances on frameshift fidelity during DNA
      replication.
AB  - The use of unequal concentrations of the four deoxynucleoside triphosphates
      (dNTPs) in DNA polymerization reactions alters base substitution error rates in a
      predictable way. Less is known about the effects of substrate imbalances on base
      addition and deletion error rates. Thus, we examined pool bias effects on
      frameshift fidelity during DNA synthesis catalyzed by replicative DNA
      polymerases. Imbalanced pools altered the frameshift fidelity of the human
      immunodeficiency virus type-1 reverse transcriptase. Both mutagenic and
      antimutagenic effects were observed for minus-one, plus-one, and minus-two
      nucleotide errors, in a highly sequence-specific manner. Most of this specificity
      can be rationalized by either of two models. One involves frameshifts initiated
      by pool bias-induced nucleotide misinsertion, and the other involves pool bias
      initiated template-primer slippage. Several examples of complex mutations were
      also recovered more than once in small mutant collections. These contained
      closely spaced single-base substitution and minus-one base frameshift changes.
      The two changes occurred at a frequency much higher than predicted if they were
      generated independently. This suggests that when the polymerase makes one
      mistake, the probability that it will make a second mistake within the next few
      incorporations increases significantly. Perturbation of dNTP pools also affected
      the frameshift fidelity of the replicative yeast DNA polymerase alpha. In
      reactions containing a low concentration of one dNTP, the error rate increased
      for one-nucleotide deletions at homopolymeric template nucleotides complementary
      to the dNTP whose concentration was low. We extended this approach to determine
      the frameshift fidelity of simian virus 40 origin-dependent semiconservative
      replication of double-stranded DNA in extracts of human cells. In reactions
      performed with an equal concentration of all four dNTPs, replication was highly
      accurate for minus-one-nucleotide errors. However, when the concentration of one
      dNTP was decreased, the replication error rate increased at complementary,
      homopolymeric template positions. This response provides an approach for
      describing frameshift accuracy during replication of the leading and lagging
      strands.

PMID- 1371273
TI  - Immunopurification and structural analysis of a putative epithelial Cl- channel
      protein isolated from bovine trachea.
AB  - We have purified to homogeneity a 38-kDa protein (called p38) from bovine
      tracheal epithelium. This protein, when reconstituted into liposomes, mediates
      stilbene disulfonate-sensitive 125I- conductive uptake. On nonreduced or
      partially reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis, this
      protein associates into a doublet of 62-64 kDa. In some experiments a multimer of
      141 kDa was also observed. Rabbit polyclonal anti-P38 antibodies have been
      produced and used to immunopurify the native transporter. Upon reconstitution of
      the immunoaffinity-purified protein into liposomes, a 260-fold enhancement of
      4,4'-bis(isothiocyano)-2,2'-stilbenedisulfonate and valinomycin-sensitive 125I-
      uptake was observed as compared to proteoliposomes containing unseparated
      material. On Western blots of total solubilized tracheal membrane proteins or
      semipurified fractions, the antibody recognized the 62-64-kDa doublet much better
      than the original 38-kDa antigen. Similar protein bands were detected in T84 and
      CFPAC cells as well. However, if apical membrane proteins were first separated by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing
      conditions, the antibody recognized major bands at 140 and approximately 240 kDa.
      Upon partial reduction, immunolabeling of these proteins diminished with the
      concomitant appearance of the 62-64-kDa doublet. Upon complete reduction, the
      appearance of 32- and 38-kDa proteins was evident with the disappearance of the
      62-64-kDa doublet. We hypothesize that the native Cl-channel is a heteromer
      containing at least four subunits connected by S-S bridges.

PMID- 1371274
TI  - The catalytic functions of chimeric reverse transcriptases of human
      immunodeficiency viruses type 1 and type 2.
AB  - The reverse transcriptases (RTs) from human immunodeficiency viruses types 1 and
      2 (HIV-1 and HIV-2, respectively) are relatively highly related yet there are
      several significant differences in their catalytic activities. In an attempt to
      relate these functional dissimilarities to the differences in amino acid
      sequences, we have employed a novel approach of constructing chimeric molecules
      composed of complementary amino acid sequences derived from the two HIV RTs.
      These recombinant proteins were analyzed for their enzymatic activities and for
      their sensitivity to tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2[1H]-one and
      thione (TIBO), which selectively inhibits only HIV-1 RT. The active chimeric RTs
      were used to map the TIBO binding site on the HIV-1 RT molecules and to localize
      the putative sequences responsible for the high RNase H activity of HIV-1 RT
      relative to that of HIV-2 RT. The results suggest that TIBO interacts with amino
      acid residues located around residue 200 within the DNA polymerase domain of HIV
      1 RT which shows a relatively low similarity to HIV-2 RT. The difference in the
      RNase H activity maps to a position in the DNA polymerase domain rather than to
      the RNase H domain. Out of the 12 chimeric RTs generated, four were either fully
      active or hyperactive, three others lost most of their catalytic activities, and
      the rest were totally inactive. The pattern of catalytic activities of these
      hybrid proteins can be explained by a model for the initial folding of HIV RTs,
      which entails the formation of three distinct and independently folded regions.
      Each region can be formed by amino acid sequences derived exclusively from either
      HIV-1 RT or HIV-2 RT.

PMID- 1371275
TI  - Differential expression of the "B" subunit of the vacuolar H(+)-ATPase in bovine
      tissues.
AB  - The B subunit is one of two nucleotide-binding polypeptides found in all members
      of the vacuolar class of H(+)-translocating ATPases. We have isolated aDNA clone
      encoding the bovine brain B (58 kDa) subunit and have deduced its amino acid
      sequence. The bovine brain amino acid sequence is 99% identical to a partial cDNA
      reported from human brain. Northern blot analysis of RNA isolated from bovine
      tissues and a bovine kidney cell line reveals that two messages of approximately
      3.2 and 2.0 kilobases (kb) are expressed in all tissues examined except brain,
      where only the 3.2-kb message can be detected. Northern blotting of RNA isolated
      from human fibroblast and human lung tumor cell lines reveals that three messages
      of approximately 6.0, 3.2, and 2.0 kb are expressed, whereas only the 3.2-kb
      message is expressed in a human brain tumor cell line. This is the first
      demonstration of tissue-specific expression of multiple forms of a vacuolar H(+)
      ATPase subunit. We have also isolated a partial cDNA clone from bovine brain
      which appears to encode an isoform of the B subunit. The deduced amino acid
      sequence is 82% identical to the major bovine brain B subunit sequence; it does
      not hybridize with either the 3.2- or 2.0-kb message on Northern blot. Southern
      blot analysis of bovine genomic DNA with probes derived from both isolated cDNAs
      indicates that the bovine B subunit is encoded by a multigene family.

PMID- 1371277
TI  - Characterization of the hemolysin transporter, HlyB, using an epitope insertion.
AB  - The prokaryotic hlyB gene product is a member of a superfamily of ATP-binding
      transport proteins that include the eukaryotic multidrug-resistance P
      glycoprotein, the yeast STE6, and the cystic fibrosis CFTR gene products
      (Juranka, P. F., Zastawny, R. L., and Ling, V. (1989) FASEB J. 3, 2583-2592).
      Previous genetic studies have indicated that HlyB is involved in the transport of
      the 107-kDa HlyA protein from Escherichia coli; however, the HlyB protein has not
      been purified for biochemical studies due to its low abundance. In this study, we
      have engineered a monoclonal antibody epitope into the C-terminal end of HlyB
      that did not destroy its function. This has allowed us to use immunological
      methods to identify and localize various molecular forms of the HlyB protein
      present in vivo.

PMID- 1371276
TI  - Heparin suppresses specific second messenger pathways for protooncogene
      expression in rat vascular smooth muscle cells.
AB  - We investigated the molecular mechanisms underlying the ability of heparin to
      inhibit vascular smooth muscle cell (VSMC) growth. Previous experiments have
      shown that heparin inhibits induction of c-fos and c-myc protooncogene mRNA in
      rat VSMC stimulated by phorbol 12-myristate 13-acetate (PMA) but not when
      stimulated by epidermal growth factor (EGF) (Pukac, L. A., Castellot, J. J.,
      Wright, T. C., Caleb, B. L., and Karnovsky, M. J. (1990) Cell Regul. 1, 435-443).
      The present experiments show that these mitogens activate distinct second
      messenger pathways in VSMC, because PMA but not EGF induction of c-fos and c-myc
      mRNA was suppressed in protein kinase C (PKC) down-regulated VSMC; this suggests
      that EGF does not act through a PKC-dependent pathway for induction of these
      genes. Heparin inhibited serum stimulation of c-fos mRNA in control VSMC, but
      heparin did not inhibit the smaller but significant serum stimulation of c-fos
      mRNA in PKC down-regulated VSMC, indicating that heparin may selectively inhibit
      PKC-dependent, but not PKC-independent, stimulation of gene expression. To
      further determine if heparin inhibits non-PKC pathways, VSMC were treated with
      dibutyryl cAMP, 3-isobutyl-1-methyl-xanthine, and Ca2+ ionophore A23187;
      stimulation of c-fos mRNA by this treatment was not inhibited by heparin. DNA
      synthesis and cell proliferation were inhibited in rat VSMC exposed briefly to
      heparin during the G0/G1 phase of the cell cycle. These experiments indicate
      heparin can act early in the cell cycle and suggest PKC-dependent but not PKC
      independent signaling pathways for gene expression are selectively sensitive to
      heparin inhibition.

PMID- 1371278
TI  - Thyroid hormone regulates the oxytocin gene.
AB  - Endocrine factors involved in the transcriptional regulation of the oxytocin (OT)
      gene were investigated in heterologous expression systems. Plasmids having a 5'
      flanking region of the rat OT gene (-363/+16) or the human OT gene (-382/+41)
      cloned in front of the firefly luciferase gene were co-transfected with an
      expression vector for the rat thyroid hormone receptor alpha in P19 embryonal
      carcinoma (EC) cells. Thyroid hormone (T3) stimulated the activity of the rat and
      human OT promoters about 10-fold. In MCF-7 breast tumor cells transfected with
      the human OT promoter-luciferase fusion gene, T3 stimulation through endogenous
      thyroid hormone receptors was about 5-fold. Co-transfection experiments in P19EC
      cells using 5' deletion mutants of the rat OT gene showed that thyroid hormone
      responsiveness was located in two regions, one located between nucleotides -195
      and -172, the other between nucleotides -172 and -148. Each region accounted for
      about 3-fold T3 stimulation. Gel retardation analysis using extracts from HeLa
      cells over-producing the c-erbA/TR alpha protein showed specific binding to the 
      172/-148 element, while no binding occurred on the -195/-172 element. The -172/
      148 element which contains the imperfect estrogen response element,
      GGTGACCTTGACC, has inverted as well as direct repeats of the TGACC motif.
      Mutagenesis of TGACC motifs separately reduced thyroid hormone responsiveness by
      about 50%. However, simultaneous mutation of two TGACC motifs abolished the
      responsiveness to T3 completely. There was no cooperativity between the activated
      thyroid hormone and estrogen receptors in transfected MCF-7 cells nor in thyroid
      hormone receptor and estrogen receptor co-transfected P19EC cells. Negative
      interactions between these two receptors were observed and gel retardation assays
      showed interaction between the two receptors proteins. It was shown in an in vivo
      experiment that treatment of rats with thyroid hormone increased hypothalamic OT
      mRNA levels, the pituitary OT content, as well as OT levels in blood. The results
      reveal thyroid hormone as a physiological regulator of OT gene expression, which
      stimulates OT promoter activity directly through interaction with a thyroid
      hormone-response element in the OT gene.

PMID- 1371279
TI  - A spontaneous mutation of integrin alpha IIb beta 3 (platelet glycoprotein IIb
      IIIa) helps define a ligand binding site.
AB  - This work characterizes a mutant integrin alpha IIb beta 3 (glycoprotein (GP) IIb
      IIIa) from a thrombasthenic patient, ET, whose platelets fail to aggregate in
      response to stimuli. The nature of defect was defined by the reduced ability of
      synthetic peptide ligands, corresponding to the carboxyl terminus of the
      fibrinogen gamma chain (gamma 402-411) and Arg-Gly-Asp (RGD), to increase the
      binding of the occupancy-dependent anti-LIBS1 antibody to mutant alpha IIb beta 3
      and the reduced binding of mutant alpha IIb beta 3 to an immobilized RGD peptide.
      In addition, ET's platelets failed to bind the ligand-mimetic monoclonal anti
      alpha IIb beta 3, PAC1. DNA sequence analysis of amplified ET genomic DNA
      revealed a single G----A base change which encoded substitution of R214 by Q in
      mature beta 3. Introduction of this point mutation into recombinant wild type
      alpha IIb beta 3 expressed in Chinese hamster ovary cells reproduced the ET
      platelet alpha IIb beta 3 deficits in binding of fibrinogen, mAb PAC1, and
      synthetic peptide ligands. Furthermore, substitution of R214 by Q in the
      synthetic peptide containing the sequence of beta 3(211-222) resulted in
      decreased ability of this peptide to block fibrinogen binding to purified alpha
      IIb beta 3. These findings suggest that substitution of beta 3 R214 by Q is
      responsible for the functional defect in alpha IIb beta 3 and that R214 is
      proximal to or part of a ligand binding domain in alpha IIb beta 3.

PMID- 1371280
TI  - Elongation factor-dependent transcript shortening by template-engaged RNA
      polymerase II.
AB  - In addition to polynucleotide polymerization, DNA polymerases and bacterial RNA
      polymerase can also remove nucleotides from the growing end of nucleic acid
      chains. For DNA polymerases this activity is an important factor in establishing
      fidelity in DNA synthesis. This report describes a novel in vitro activity of RNA
      polymerase II whereby it cleaves an RNA chain contained within an active
      elongation complex. These elongation complexes are arrested at a previously
      identified, naturally occurring transcriptional pause site in a human gene. The
      new 3'-end revealed by this cleavage remains associated with an active elongation
      complex and is capable of being extended by RNA polymerase II. Nascent RNA
      cleavage is evident after removal of free nucleotides and is dependent upon a
      divalent metal cation and transcription elongation factor SII. This function of
      SII could be important in its function as an activator of transcription
      elongation. It is also possible that the transcript cleavage activity of RNA
      polymerase II represents a proofreading function of the enzyme.

PMID- 1371281
TI  - Characterization and dynamics of O-linked glycosylation of human cytokeratin 8
      and 18.
AB  - The glycosylation of human cytokeratin (CK) 8 and 18 was studied after metabolic
      labeling of HT29 colonic cells with [3H]glucosamine. Labeling of CK8/18 was not
      inhibited by tunicamycin, suggesting that glycosylation was not N-linked. Acid
      hydrolysis of CK8 and CK18, purified from [3H]glucosamine-labeled cells,
      generated free glucosamine. In the presence of UDP-[3H]galactose,
      galactosyltransferase catalyzed the labeling of cytokeratin 8 and 18. beta
      Elimination of the [3H]galactose- labeled CK8/18 generated the disaccharide N
      acetyllactosaminitol, indicating that cytokeratin 8 and 18 contain single O
      linked N-acetylglucosamine residues. Using chemical analysis, the stoichiometry
      of glycosylation was found to be 1.5 and 2 molecules of N
      acetylglucosamine/protein molecule of CK8 and CK18, respectively. Peptide maps of
      [3H]glucosamine-labeled CK8/18 showed that multiple peptides were labeled with
      the amino sugar. The biosynthetic and degradation rates of the carbohydrate
      moiety were faster than the protein core as determined by metabolic radiolabeling
      or pulse-chase experiments, respectively. Our results show that CK8 and 18 are
      glycosylated at multiple sites with a single O-linked N-acetylglucosamine.
      Furthermore, CK8/18 glycosylation is a dynamic process which is likely to have
      functional relevance.

PMID- 1371282
TI  - Expression and characterization of a cDNA for rat kidney biliverdin reductase.
      Evidence suggesting the liver and kidney enzymes are the same transcript product.
AB  - Biliverdin reductase is a unique dual cofactor- and pH-dependent enzyme that
      converts biliverdin to bilirubin and displays extensive inter-organ pI and
      molecular weight microheterogeneity. Presently we have explored the molecular
      basis for these properties. The amino acid composition and the sequences of NH2
      termini plus five tryptic fragments of purified rat liver and kidney enzymes were
      obtained. A 62-nucleotide DNA probe was designed and in combination with antibody
      was used to screen a rat kidney cDNA library. A cDNA sequence of 1108 base pairs
      (bp) containing an 885-bp open reading frame was generated. The cloned cDNA probe
      detected a single mRNA of approximately 1500 bp in liver and kidney. The open
      reading frame encodes a 295 amino acid protein. Methionine and aspartic acid
      residues at positions 1 and 2 of the deduced protein are removed during
      processing. The deduced amino acid composition of the mature protein closely
      matched that of the purified rat liver and kidney enzymes. All liver peptides
      were found in the deduced amino acid sequence of kidney enzyme and the NH2
      termini of both enzymes were identical. The expressed protein co-migrated with
      purified reductase and was recognized by antiserum to the enzyme. The expressed
      reductase displayed two distinct pH optima using a different cofactor at each pH:
      NADH at the lower pH 6.7-6.9 range and NADPH at pH 8.5-8.7. The findings suggest
      that the liver and kidney enzymes are the products of the same transcript(s) and
      that their microheterogeneity may reflect tissue-specific post-translational
      modifications.

PMID- 1371283
TI  - A monoclonal antibody recognizes an epitope in the first extracellular loop of
      the plasma membrane Ca2+ pump.
AB  - A monoclonal antibody against the human erythrocyte Ca2+ pump (1E4) reacted with
      the enzyme in intact erythrocytes. Using trypsinized preparations of the pump the
      antibody only reacted with the N-terminal fragments of 33.5 and 35 kDa. The
      fragments span from the N terminus (35 kDa) or from residue 19 (33.5 kDa) to
      residue 314 of the hPMCA4 isoform of the pump. Exhaustive degradation with a
      number of agents produced smaller peptides which reacted with the antibody.
      Sequencing analysis on two chymotryptic fragments of 8.8 and 13.5 kDa identified
      the epitope in an approximately 80-residue domain beginning with Gly-81. Two
      peptides corresponding to the putative extramembrane portions of this region of
      the pump were synthesized. The antibody reacted with one of them, spanning
      residues Phe-121 to Gly-152 and containing the first putative external loop of
      the pump. Peptides corresponding to overlapping portions of this peptide were
      synthesized, leading to the location of the epitope in a 13-residue sequence (Glu
      130 to Glu-142) in the first predicted extracellular loop (Verma, A. K., Filoteo,
      A. G., Stanford, D. R., Wieben, E. D., Strehler, E. E., Fischer, R., Heim, R.,
      Vogel, G., Mathews, S., Strehler-Page, M-A., James, P., Vorherr, T., Krebs, J.,
      Penniston, J. T., and Carafoli, E. (1988) J. Biol. Chem. 263, 14152-14159).

PMID- 1371284
TI  - Human lipoprotein lipase. Analysis of the catalytic triad by site-directed
      mutagenesis of Ser-132, Asp-156, and His-241.
AB  - Lipoprotein lipase (LPL) plays a central role in normal lipid metabolism as the
      key enzyme involved in the hydrolysis of triglycerides present in chylomicrons
      and very low density lipoproteins. LPL is a member of a family of hydrolytic
      enzymes that include hepatic lipase and pancreatic lipase. Based on primary
      sequence homology of LPL to pancreatic lipase, Ser-132, Asp-156, and His-241 have
      been proposed to be part of a domain required for normal enzymic activity. We
      have analyzed the role of these potential catalytic residues by site-directed
      mutagenesis and expression of the mutant LPL in human embryonic kidney-293 cells.
      Substitution of Ser-132, Asp-156, and His-241 by several different residues
      resulted in the expression of an enzyme that lacked both triolein and tributyrin
      esterase activities. Mutation of other conserved residues, including Ser-97, Ser
      307, Asp-78, Asp-371, Asp-440, His-93, and His-439 resulted in the expression of
      active enzymes. Despite their effect on LPL activity, substitutions of Ser-132,
      Asp-156, and His-241 did not change either the heparin affinity or lipid binding
      properties of the mutant LPL. In summary, mutation of Ser-132, Asp-156, and His
      241 specifically abolishes total hydrolytic activity without disrupting other
      important functional domains of LPL. These combined results strongly support the
      conclusion that Ser-132, Asp-156, and His-241 form the catalytic triad of LPL and
      are essential for LPL hydrolytic activity.

PMID- 1371285
TI  - DNA chain termination activity and inhibition of human immunodeficiency virus
      reverse transcriptase by carbocyclic 2',3'-didehydro-2',3'-dideoxyguanosine
      triphosphate.
AB  - Carbocyclic 2',3'-didehydro-2',3'-dideoxyguanosine (carbovir, NSC 614846) is an
      anti-retroviral agent that may be useful in the treatment of AIDS. We have
      examined the ability of (-)-enantiomeric carbovir triphosphate to inhibit human
      immunodeficiency virus type 1 (HIV-1) reverse transcriptase (EC 2.7.7.49). A
      comparison of inhibition kinetics was made with 3'-azido-2',3'-dideoxythymidine
      triphosphate and phosphonoformate. Inhibition of the reverse transcriptase was
      evaluated using poly(rA).oligo(dT)12-18, poly(rC).oligo(dG)12-18, or influenza
      virion RNA template with a specific oligodeoxynucleotide as primer. (-)-Carbovir
      5'-triphosphate was shown to be a potent inhibitor of HIV-1 reverse transcriptase
      with an apparent Ki similar to that of 3'-azido-2',3'-dideoxythymidine
      triphosphate. Chain elongation studies utilizing an MS2 RNA template showed that
      (-)-carbovir 5'-triphosphate terminated transcription at positions identical to
      those where dideoxy-GTP terminated. This indicates that (-)-carbovir 5'
      monophosphate is incorporated into the newly synthesized DNA and terminates
      transcription at that point. We conclude that (-)-carbovir 5'-triphosphate is a
      potent inhibitor of the HIV-1 reverse transcriptase enzyme and that (-)-carbovir
      most likely inhibits HIV by activity at the triphosphate level by a combination
      of direct competition for binding of the natural deoxynucleoside triphosphates to
      the reverse transcriptase and chain termination.

PMID- 1371286
TI  - A single locus encodes both phenylalanine hydroxylase and tryptophan hydroxylase
      activities in Drosophila.
AB  - We have used a full-length clone encoding rabbit tryptophan hydroxylase (TRH) to
      isolate the Drosophila homologue (DTPH). Southern analysis of Drosophila genomic
      DNA reveals a pattern indicative of a single gene. The single transcript is
      expressed in adult head and body mRNA but is also detected in mRNA from early
      embryos. The embryonic transcript is ubiquitously expressed and appears to
      concentrate in yolk granules. In situ hybridization of TRH-homologous antisense
      RNA probe to sectioned tissue from third instar larvae demonstrated the presence
      of this transcript in fat body and cuticular tissue. Developmental immunoblot
      analysis using antibodies raised against a beta-galactosidase-Drosophila fusion
      protein revealed a 45-kDa embryonic protein also detected in female abdomens and
      a 50-kDa protein found in larval and adult stages. Immunocytochemical analysis of
      the Drosophila protein in the larval central nervous system showed that it
      appeared to be present in both serotonin- and catecholamine-containing neurons. A
      nonfusion protein generated in Escherichia coli hydroxylates both tryptophan and
      phenylalanine. We propose that there are only two aromatic amino acid hydroxylase
      genes in Drosophila: one encoding tyrosine hydroxylase, DTH, and DTPH, a gene
      encoding both tryptophan and phenylalanine hydroxylase activities.

PMID- 1371287
TI  - Do the ends justify the mean? Proline mutations at the ends of the keratin coiled
      coil rod segment are more disruptive than internal mutations.
AB  - Intermediate filament (IF) assembly is remarkable, in that it appears to be self
      driven by the primary sequence of IF proteins, a family (40-220 kd) with diverse
      sequences, but similar secondary structures. Each IF polypeptide has a central
      310 amino acid residue alpha-helical rod domain, involved in coiled-coil dinner
      formation. Two short (approximately 10 amino acid residue) stretches at the ends
      of this rod are more highly conserved than the rest, although the molecular basis
      for this is unknown. In addition, the rod is segmented by three short nonhelical
      linkers of conserved location, but not sequence. To examine the degree to which
      different conserved helical and nonhelical rod sequences contribute to dimer,
      tetramer, and higher ordered interactions, we introduced proline mutations in
      residues throughout the rod of a type I keratin, and we removed existing proline
      residues from the linker regions. To further probe the role of the rod ends, we
      introduced more subtle mutations near the COOH-terminus. We examined the
      consequences of these mutations on (a) IF network formation in vivo, and (b) 10
      nm filament assembly in vitro. Surprisingly, all proline mutations located deep
      in the coiled-coil rod segment showed rather modest effects on filament network
      formation and 10-nm filament assembly. In addition, removing the existing proline
      residues was without apparent effect in vivo, and in vitro, these mutants
      assembled into 10-nm filaments with a tendency to aggregate, but with otherwise
      normal appearance. The most striking effects on filament network formation and IF
      assembly were observed with mutations at the very ends of the rod. These data
      indicate that sequences throughout the rod are not equal with respect to their
      role in filament network formation and in 10-nm filament assembly. Specifically,
      while the internal rod segments seem able to tolerate considerable changes in
      alpha-helical conformation, the conserved ends seem to be essential for creating
      a very specific structure, in which even small perturbations can lead to loss of
      IF stability and disruption of normal cellular interactions. These findings have
      important implications for the disease Epidermolysis Bullosa Simplex, arising
      from point mutations in keratins K5 or K14.

PMID- 1371289
TI  - On the ultrastructure of hyalin, a cell adhesion protein of the sea urchin embryo
      extracellular matrix.
AB  - Hyalin is a large (ca. 350 x 10(3) kD by gel electrophoresis) molecule that
      contributes to the hyalin layer surrounding the sea urchin embryo. In previous
      work a mAb (McA Tg-HYL), specific for hyalin, was found to inhibit cell-hyalin
      adhesion and block morphogenesis of whole embryos (Adelson, D. L., and T. D.
      Humphreys. 1988. Development. 104:391-402). In this report, hyalin ultrastructure
      was examined via rotary shadowing. Hyalin appeared to be a filamentous molecule
      approximately 75-nm long with a globular "head" about 12 nm in diameter that
      tended to form aggregates by associating head to head. Hyalin molecules tended to
      associate with a distinct high molecular weight globular particle ("core"). In
      fractions containing the core particle often more than one hyalin molecule were
      seen to be associated with the core. The core particle maintained a tenacious
      association with hyalin throughout purification procedures. The site(s) of McA Tg
      HYL binding to the hyalin molecule were visualized by decorating purified hyalin
      with the antibody and then rotary shadowing the complex. In these experiments,
      McA Tg-HYL attached to the hyalin filament near the head region in a pattern
      suggesting that more than one antibody binding site exists on the hyalin
      filament. From the ultrastructural data and from the cell adhesion data presented
      earlier we conclude that hyalin is a filamentous molecule that binds to other
      hyalin molecules and contains multiple cell binding sites. Attempts were made to
      demonstrate the existence of lower molecular weight hyalin precursors. Whilst no
      such precursors could be identified by immunoprecipitation of in vivo labeled
      embryo lysates, immunoprecipitation of in vitro translation products suggested
      such precursors (ca 40 x 10(3) kD) might exist.

PMID- 1371290
TI  - Benign prostatic hyperplasia: new insights.

PMID- 1371288
TI  - Progressive stages of "transdifferentiation" from epidermal to mesenchymal
      phenotype induced by MyoD1 transfection, 5-aza-2'-deoxycytidine treatment, and
      selection for reduced cell attachment in the human keratinocyte line HaCaT.
AB  - The ability of the myogenic determination gene (MyoD1) to convert differentiating
      human keratinocytes (HaCaT cell-line) to the myogenic pathway and the effect of
      MyoD1 on the epidermal phenotype was studied in culture and in surface
      transplants on nude mice. MyoD1 transfection induced the synthesis of myosin,
      desmin, and vimentin without substantially altering the epidermal differentiation
      properties (morphology, keratin profile) in vitro nor epidermal morphogenesis
      (formation of a complex stratified squamous epithelium) in surface transplants,
      demonstrating the stability of the keratinocyte phenotype. 5-Aza-CdR treatment of
      these MyoD1-transfected cells had little effect on the cultured cells but a
      morphologically unstructured epithelium was formed with no indications of typical
      cell layers including cornification. Since prevention of epidermal strata in
      transplants was not accompanied by blocked epidermal differentiation markers
      (keratins K1 and K10, involucrin, and filaggrin), the dissociation of
      morphogenesis and expression of these markers argues for independently controlled
      processes. A subpopulation of less adhesive cells, isolated from the 5-aza-CdR
      treated MyoD1-transfectants, had lost most epithelial characteristics in culture
      (epidermal keratins, desmosomal proteins, and surface-glycoprotein Gp90) and had
      shifted to a mesenchymal/myogenic phenotype (fibroblastic morphology,
      transactivation of Myf3 and myogenin, expression of myosin, desmin, vimentin, and
      Gp130). Moreover, the cells had lost the ability to stratify and remained as a
      monolayer of flat elongated cells in transplants. These subsequent changes from a
      fully differentiated keratinocyte to a mesenchymal/myogenic phenotype strongly
      argue for a complex "transdifferentiation" process which occurred in the original
      monoclonal human epidermal HaCaT cells.

PMID- 1371291
TI  - Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic
      dihydrotestosterone in men with benign prostatic hyperplasia.
AB  - The oral administration of finasteride, a 4-aza-steroid inhibitor of 5 alpha
      reductase, decreases serum dihydrotestosterone levels, but has little effect on
      serum testosterone. The current study was designed to assess the effect of
      finasteride on dihydrotestosterone levels in the prostates of men with benign
      prostatic hyperplasia. In a double blind, placebo-controlled study, 69 men with
      symptomatic prostatic hyperplasia were treated with placebo or 1, 5, 10, 50, or
      100 mg/day finasteride for 7 days before transurethral resection of the prostate.
      In the placebo group the mean concentration of prostatic dihydrotestosterone was
      10.3 +/- 0.6 nmol/kg (+/- SE), and the mean concentration of testosterone was 0.7
      +/- 0.1 nmol/kg. After 7 days of treatment with all doses of finasteride,
      prostatic dihydrotestosterone declined to 15% or less of control levels, and the
      testosterone concentration increased in a reciprocal fashion. Compared to the
      placebo group, there was no significant difference in the mean prostatic
      dihydrotestosterone level achieved in any of the finasteride-treated groups.
      However, prostatic dihydrotestosterone levels were lower in the groups receiving
      higher doses of the drug. In two additional patients, finasteride treatment for 2
      days also caused a decrease in prostatic dihydrotestosterone levels. No
      significant adverse experiences occurred during the study. We conclude that
      finasteride causes profound decrease in prostatic dihydrotestosterone.

PMID- 1371292
TI  - Follicular fluid insulin-like growth factor binding protein profiles in
      polycystic ovary syndrome.
AB  - Insulin-like growth factor binding proteins (IGFBPs) are believed to modulate the
      actions of IGF-I and IGF-II at the cellular level. We have examined, by Western
      ligand blot analysis, the IGFBP profiles in follicular fluid (FF) from patients
      with polycystic ovarian syndrome (a disorder of ovarian folliculogenesis),
      compared to FF from atretic and developing (estrogenic) follicles from normally
      cycling women. IGFBPs with apparent mol wts (Mr) of 41.5, 38.5, 31, 28, and 24kDa
      were detected in PCOS FF. The profile of IGFBPs in PCOS FF was indistinguishable
      from that seen in atretic follicles in cycling women. However, higher levels of
      the 31, 28, and 24kDa IGFBPs were observed in PCOS FF, compared to healthy,
      estrogenic follicles. Using specific antisera, the 41.5 and 38.5kDa IGFBPs were
      identified as IGFBP-3, and the 31kDa IGFBP as IGFBP-2. IGFBP-1, however, was not
      appreciably detectable in PCOS FF, by Western ligand blotting. Endoglycosidase F
      treatment of FF decreased the Mr of the 28kDa IGFBP to 24kDa, and neither the
      28kDa nor the 24kDa IGFBP was immunoprecipitated by antibodies to IGFBP-1, -2, or
      -3. Elevated levels of 28kDa and 24kDa IGFBPs in PCOS FF may represent
      glycosylated and core forms of IGFBP-4. The data presented herein show that in
      PCOS FF, as well as in FF from atretic follicles from normally cycling women,
      IGFBP-2 and 28 and 24kDa IGFBPs are present in greater amounts, compared to
      levels in FF from healthy, developing, estrogenic follicles. One or more of the
      IGFBP species elevated in atretic and PCOS follicles may bind IGFs in FF, thereby
      inhibiting IGF action on the granulosa during normal folliculogenesis.

PMID- 1371294
TI  - Skin adnexal tumours.

PMID- 1371293
TI  - Limulus amoebocyte lysate assay in the diagnosis of peritonitis in patients
      receiving continuous ambulatory peritoneal dialysis.
AB  - AIMS: To evaluate the Limulus amoebocyte lysate (LAL) assay for differentiating
      Gram positive from Gram negative peritonitis in patients receiving continuous
      ambulatory peritoneal dialysis (CAPD). METHODS: One hundred and six patients with
      suspected peritonitis were studied. LAL assay was performed by adding 0.1 ml of
      CAPD fluid to 0.1 ml of LAL reagent and incubating in a heating block for 60
      minutes at 37 degrees C. The sensitivity of the reaction was determined by: (i)
      diluting endotoxin in distilled water and used (filter sterilised) peritoneal
      dialysis fluid; and (ii) diluting a broth culture of E coli used in peritoneal
      dialysis fluid. A positive LAL assay was defined as the constant stability of the
      clot through an inversion of 180 degrees. RESULTS: Compared with bacterial
      culture, the LAL assay had a sensitivity of 65% and a specificity of 98%. The
      sensitivity of microscopy compared with culture of Gram negative organisms was
      76%; overall sensitivity of microscopy in comparison was 80%. CONCLUSIONS: The
      Gram stain was more sensitive than has previously been reported; the LAL assay
      was specific but insensitive for the diagnosis of CAPD peritonitis. There was a
      correlation between reduced leucocyte count and culture; this was reduced in
      cases from which Gram negative organisms had been isolated. It is recommended
      that laboratories evaluate their Gram stain procedure to improve its sensitivity
      because the LAL assay is not a satisfactory substitute.

PMID- 1371295
TI  - Biomodulators in cancer treatment.

PMID- 1371296
TI  - Effect of coculture of rodent mast cells with murine chronic graft-versus-host
      disease (cGVHD)-derived fibroblasts.
AB  - We investigated whether murine chronic graft-versus-host disease (cGVHD)-derived
      skin fibroblasts maintain the viability and functional activity of rat peritoneal
      connective tissue-mast cells (CTMCs) and whether they affect the change in
      phenotype of mouse bone marrow-derived mast cells (BMMCs). Skin fibroblasts were
      isolated before the development of fibrosis (day 5), during overt fibrosis (day
      28), and after recovery from fibrosis (day 120). cGVHD fibroblasts of days 5 and
      28 exhibited enhanced proliferation, a property that was maintained through
      several subcultures. CTMCs adhered to the same extent, did not divide, and
      maintained their viability in all the different cultures. When CTMCs were
      activated with compound 48/80, they released approximately 80% of their histamine
      content, indicating that coculture with cGVHD fibroblasts did not adversely
      affect CTMC function. The amount of histamine found in the medium of 8 days
      CTMC/cGVHD fibroblast coculture was similar to that found in control culture.
      These findings suggest that the degranulation of dermal MCs, characteristic of
      cGVHD, is not due to a direct activating effect of the cGVHD fibroblasts on the
      MCs. BMMCs seeded on cGVHD fibroblasts acquired the capacity for safranin
      staining and increased their histamine content, indicative of a change to CTMCs.
      Thus, cGVHD fibroblasts are able to provide a microenvironment adequate for
      maintaining viability and activity of CTMCs and for promoting maturation and
      change in phenotype of BMMCs.

PMID- 1371297
TI  - Recombinant hemopoietic growth factors: comparative hemopoietic response in
      younger and older subjects.
AB  - OBJECTIVE: To study the effectiveness of hemopoietic growth factors in older
      patients. DESIGN: Literature review. All articles published in English language
      between 1987 and 1990 were reviewed. Those reporting studies without age limits
      as entry criteria and describing the effects of growth factors in individual
      patients were suitable for analysis. Bone marrow transplantation related articles
      were excluded. MAIN OUTCOME MEASURES: The meanfold increase of granulocytes for
      Granulocyte-Colony Stimulating Factor, Granulocyte Macrophage-Colony Stimulating
      Factor, and Interleukin 3 and of hemoglobin for erythropoietin were compared in
      subjects younger and older than 65, by Mann-Whitney U test. RESULTS: Of 68
      studies, 23 were suitable for analysis. These included patients with
      myelodysplastic syndromes, aplastic anemia, chemotherapy-induced
      myelosuppression, chronic granulocytopenia, anemia, and myelosuppression of
      malignancies and of chronic disease. Of 204 patients, 67 were 65 years of age or
      older and 42 were over 70. No difference was seen in meanfold increase of
      granulocyte and hemoglobin in time of response to growth factors or in response
      in presence of an absolute neutrophil count lower than 1000/microliters between
      younger and older patients. CONCLUSION: Early response to hemopoietic growth
      factors appears well maintained with advanced age. Prospective studies of the
      prolonged effects of these factors in older and younger patients are needed.

PMID- 1371298
TI  - Effects of a new immunosuppressive agent, FK506, in rats with active Heymann
      nephritis.
AB  - FK506 is a recently-developed immunosuppressive drug. The aim of the present work
      was to investigate the effects of FK506 in experimental autoimmune
      glomerulonephritis (active Heymann nephritis) in rats. Active Heymann nephritis
      was induced in female Lewis rats by two immunizations with the homologous brush
      border vesicles (BBVs) at day 0 and day 28 (groups I, II, V, and VI). Rats of
      groups III and IV received the third immunization at day 56. In rats of groups I
      and III, FK506 was injected (1 mg/kg/day IM) from day 0 for 14 days. In rats of
      groups II and IV, significant proteinuria was observed (group II, 112.8 mg/16
      hours; group IV, 55.4 mg/16 hours) at the time the rats were killed (day 84).
      Coarse subepithelial immune deposits (IDs) were found in these rats. In contrast,
      urinary protein excretion remained within normal range (less than 3.0 mg/16
      hours) in groups I and III rats, and tiny subepithelial IDs were only
      occasionally seen. Circulating anti-BBV antibody levels were markedly lower in
      group I and III rats than in those of groups II and IV during the period between
      day 14 and day 56. To investigate the effects of FK506 on the proteinuric rats,
      FK506 (1 mg/kg/day, IM) was administered every day for 2 weeks beginning on day
      56 (group V).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371299
TI  - Synergistic interaction of bacterial lipopolysaccharide and the monocyte
      macrophage colony-stimulating factor: potential quantitative and qualitative
      changes in macrophage-produced cytokine bioactivity.
AB  - In this brief definitive report, we show that over a 6-h period and under serum
      free conditions, recombinant monocyte-macrophage colony-stimulating factor 1
      (rCSF-1) and lipopolysaccharide (LPS) synergize and induce macrophages to express
      higher levels of mRNA for interleukin 1 alpha (IL-1 alpha), IL-1 beta, tumor
      necrosis factor alpha (TNF-alpha), and IL-6 and to release more bioactivity than
      macrophages treated with LPS alone. This synergy was regulated by the amount of
      LPS in the culture medium. Paraformaldehyde-fixed macrophages like-wise showed
      augmentation of IL-1 activity, but whereas all of the bioactivity associated with
      the fixed macrophages could be neutralized by anti-IL-1 alpha antibody only
      approximately 40% of the supernate activity could be attributed to IL-1 alpha.
      Preliminary data suggest that the augmenting effect induced by CSF-1 cannot be
      explained solely on a quantitative basis because the addition of rIL-1 alpha to
      supernates of macrophages treated with LPS alone or with the combination of LPS
      and CSF-1 resulted in an increase in thymocyte mitogenic activity to a level that
      could not be explained on an additive basis. Although the supernates contained
      TNF and IL-6, antibody neutralization assays made it unlikely that these were
      directly responsible for the augmenting effect. These results suggest that CSF-1
      not only enhances basic genetic responses induced by LPS alone but also may
      induce a mechanism that amplifies cytokine bioactivity.

PMID- 1371300
TI  - Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40
      activated naive human B cells to secrete immunoglobulin A.
AB  - In the present report, we have investigated the in vitro differentiation of
      surface(s) sIgD+ and sIgD- human B cells into Ig-secreting cells in response to
      various stimuli. sIgD+ B cells homogeneously expressed some of the antigens
      identifying mantle zone B cells, but lacked expression of germinal center
      markers, thus confirming that the B cell populations positively selected on the
      basis of sIgD expression were highly enriched for naive B lymphocytes.
      Conversely, sIgD- B cells expressed some of the antigens specifically associated
      with germinal center B cells. T cell-independent differentiation of sIgD+ and
      sIgD- B cells could be achieved by simultaneous crosslinking of sIgs and CD40 in
      the presence of a mouse Ltk- cell line stably expressing human CDw32/Fc gamma RII
      (CDw32 L cells). In this experimental system, sIgD+ B cells were exclusively
      proned for IgM synthesis, whereas sIgD- B cells produced IgG, IgM, and IgA. Both
      the human and viral forms of interleukin 10 (IL-10) strongly increased the Ig
      secretion by sIgD+ and sIgD- B cells simultaneously activated through sIgs and
      CD40. IgM and IgG constituted the predominant Ig isotype produced by sIgD+ and
      sIgD- B cells, respectively, in response to IL-10. sIgD+ B cells could be induced
      for IgA synthesis upon co-culturing with transforming growth factor beta (TGF
      beta) and IL-10, in the presence of an anti-CD40 monoclonal antibody presented by
      the CDw32 L cells. In contrast, TGF-beta suppressed the IL-10-mediated IgG, IgM,
      and IgA secretions by sIgD- B cells. sIgD+ B cells could not be induced for IgA
      synthesis by TGF-beta and IL-10 after crosslinking of their sIgs, suggesting that
      ligation of CD40 was one of the obligatory signals required for commitment of
      naive B cells to IgA secretion. Limiting dilution experiments indicated that the
      IgA-potentiating effect of TGF-beta was due to its capacity to increase the
      frequency of IgA-producing cells, most likely as a consequence of class
      switching. Taken together, our data strongly suggest that TGF-beta is involved in
      the regulation of IgA isotype selection in humans.

PMID- 1371301
TI  - Evidence of a natural killer (NK) cell repertoire for (allo) antigen recognition:
      definition of five distinct NK-determined allospecificities in humans.
AB  - Previous studies indicated that CD3-CD16+ natural killer (NK) cells are capable
      of specific alloantigen recognition. Thus, alloreactive NK clones lysed normal
      allogeneic target cells (phytohemagglutinin [PHA] blasts) bearing the stimulating
      alloantigen but did not lyse autologous cells or the majority of unrelated
      allogeneic cells. In this study we investigated whether NK cells isolated from
      single individuals could exhibit different allospecificities. To this end, we
      derived large numbers of CD3-CD16+ clones (in the presence of PHA) from fresh CD3
      peripheral blood lymphocytes. Cloning efficiencies ranged between 5 and 10%. The
      resulting CD3-CD16+ clones were tested for their reactivity against a panel of
      allogeneic PHA blasts (derived from six donors). In a given individual (A), four
      distinct groups of clones could be identified according to their pattern of
      reactivity (over 400 clones have been analyzed). Clones that could be assigned to
      one or another group of specificity represented 36% of all clones derived from
      this donor. The remaining clones did not display cytolytic activity against any
      of the allogeneic target cells used in the panel. None of the clones lysed
      autologous (A) PHA blasts, yet, these cells were lysed by the representative
      clones G10 and H12 specific for donor A. Clones displaying a cytolytic pattern of
      reactivity identical to that defined for donor A were present in other
      individuals studied, however not all groups of allospecific clones were
      necessarily represented in different individuals. Allospecific clones belonging
      to the various groups were homogeneous in the expression of EB6/GL183-triggering
      surface molecules, and could thus be assigned to one or another of the previously
      defined subsets of NK cells. Genetic analysis of the new NK-defined alloantigens
      was performed in representative families. The corresponding characters were found
      to segregate independently and, at least for three of them, an autosomic
      recessive type of inheritance could be demonstrated. Moreover, the comparative
      analysis of the segregation of the major histocompatibility complex haplotypes
      and the recessive or dominant alleles of the genes governing the five
      specificities analyzed indicated that there is no independent sampling between
      the two genetic traits, thus suggesting that the genes regulating the NK-defined
      specificities are carried by chromosome 6. Finally, some donors expressed more
      than one specificity, thus providing evidence for an NK-defined complex
      haplotype.

PMID- 1371302
TI  - Growth factor-dependent inhibition of normal hematopoiesis by N-ras antisense
      oligodeoxynucleotides.
AB  - To determine whether N-ras expression is required at specific stages of the
      process of in vitro normal human hematopoiesis, adherent- and T lymphocyte
      depleted mononuclear marrow cells (A-T-MNC) or highly purified progenitors (CD34+
      cells) were cultured in semisolid medium, under conditions that favor the growth
      of specific progenitor cell types, after exposure to N-ras sense and antisense
      oligodeoxynucleotides. N-ras antisense, but not sense, oligodeoxynucleotide
      treatment of A-T-MNC and CD34+ cells resulted in a significantly decreased number
      of granulocyte/macrophage colony-forming units (CFU-GM) induced by interleukin 3
      (IL-3) or granulocyte/macrophage colony-stimulating factor (GM-CSF) and of
      macrophage colonies (CFU-M) induced by M-CSF, but not of granulocytic colonies
      induced with G-CSF or IL-5. However, the same treatment significantly inhibited
      colony formation induced by each of the above factors in combination with IL-3.
      Megakaryocytic colony (CFU-Meg) formation from A-T-MNC or CD34+ cells in the
      presence of IL-6 + IL-3 + erythropoietin (Epo) was also markedly decreased after
      antisense oligodeoxynucleotide treatment. Erythroid colonies derived from A-T-MNC
      in the presence of Epo (CFU-E) were not inhibited upon antisense treatment,
      whereas those arising from A-T-MNC or CD34+ cells in the presence of IL-3 + Epo
      (BFU-E) were markedly affected. These results are consistent with the hypothesis
      that distinct signal transduction pathways, involving N-ras or not, are activated
      by different growth factors in different hematopoietic progenitor cells.

PMID- 1371303
TI  - Preferential V beta gene usage and lack of junctional sequence conservation among
      human T cell receptors specific for a tetanus toxin-derived peptide: evidence for
      a dominant role of a germline-encoded V region in antigen/major
      histocompatibility complex recognition.
AB  - To investigate the structural and genetic basis of the T cell response to defined
      peptide/major histocompatibility (MHC) class II complexes in humans, we
      established a large panel of T cell clones (61) from donors of different HLA-DR
      haplotypes and reactive with a tetanus toxin-derived peptide (tt830-844)
      recognized in association with most DR molecules (universal peptide). By using a
      bacterial enterotoxin-based proliferation assay and cDNA sequencing, we found
      preferential use of a particular V beta region gene segment, V beta 2.1, in three
      of the individuals studied (64%, n = 58), irrespective of whether the peptide was
      presented by the DR6wcI, DR4w4, or DRw11.1 and DRw11.2 alleles, demonstrating
      that shared MHC class II antigens are not required for shared V beta gene use by
      T cell receptors (TCRs) specific for this peptide. V alpha gene use was more
      heterogeneous, with at least seven different V alpha segments derived from five
      distinct families encoding alpha chains able to pair with V beta 2.1 chains to
      form a tt830-844/DR-specific binding site. Several cases were found of clones
      restricted to different DR alleles that expressed identical V beta and (or very
      closely related) V alpha gene segments and that differed only in their junctional
      sequences. Thus, changes in the putative complementary determining region 3
      (CDR3) of the TCR may, in certain cases, alter MHC specificity and maintain
      peptide reactivity. Finally, in contrast to what has been observed in other
      defined peptide/MHC systems, a striking heterogeneity was found in the junctional
      regions of both alpha and beta chains, even for TCRs with identical V alpha
      and/or V beta gene segments and the same restriction. Among 14 anti-tt830-844
      clones using the V beta 2.1 gene segment, 14 unique V beta-D-J beta junctions
      were found, with no evident conservation in length and/or amino acid composition.
      One interpretation for this apparent lack of coselection of specific junctional
      sequences in the context of a common V element, V beta 2.1, is that this V region
      plays a dominant role in the recognition of the tt830-844/DR complex.

PMID- 1371304
TI  - Anchoring pockets in human histocompatibility complex leukocyte antigen (HLA)
      class I molecules: analysis of the conserved B ("45") pocket of HLA-B27.
AB  - Dissection of the peptide binding grooves of seven subtypes of human
      histocompatibility leukocyte antigen (HLA)-B27 into the six specificity pockets
      defined by the 2.6-A structure of HLA-A*0201 revealed just one pocket, the B
      ("45") pocket, that is conserved among all the HLA-B27 subtypes. Functional
      studies of mutant HLA-B*2705 molecules with point substitutions in residues of
      the B pocket show that this structure, and the glutamine residue at position 45
      in particular, plays a critical role in cell surface expression, peptide binding,
      and in the presentation of both exogenous and endogenous peptides by HLA-B*2705.
      We predict that the B pocket of HLA-B*2705 interacts with an amino acid side
      chain that anchors peptides in the binding groove, and that this peptide motif is
      present in most endogenously processed peptides that bind to all seven subtypes
      of HLA-B27.

PMID- 1371306
TI  - Clonal deletion of postthymic T cells: veto cells kill precursor cytotoxic T
      lymphocytes.
AB  - Veto cell-mediated suppression of cytotoxic T lymphocyte (CTL) responses has been
      proposed as one mechanism by which self-tolerance is maintained in mature T cell
      populations. We have previously reported that murine bone marrow cells cultured
      in the presence of high-dose interleukin 2 (IL-2) (activated bone marrow cells
      [ABM]) mediate strong veto suppressor function. To examine mechanisms by which
      ABM may suppress precursor CTL (p-CTL) responses, we used p-CTL generated from
      spleen cells of transgenic mice expressing a T cell receptor specific for H-2 Ld.
      It was demonstrated that the cytotoxic response by these p-CTL after stimulation
      with irradiated H-2d/k spleen cells was suppressed by DBA/2 (H-2d) ABM, but not
      by B10.BR (H-2k) ABM or dm1 (Dd, Ld mutant) ABM. Flow cytometry analysis with
      propidium iodide staining revealed that these p-CTL were specifically deleted by
      incubation with H-2d ABM, but not with H-2k ABM. These data indicate that ABM
      veto cells kill p-CTL with specificity for antigens expressed on the surface of
      the ABM, and that the mechanism for veto cell activity of ABM is clonal deletion
      of p-CTL.

PMID- 1371305
TI  - Alloreactive cytotoxic T lymphocytes recognize epitopes determined by both the
      alpha helices and beta sheets of the class I peptide binding site.
AB  - A chimeric class I glycoprotein was created to investigate the functional
      contribution of the alpha helices and the beta-pleated sheets in forming the
      antigen recognition site (ARS) of antigen-presenting molecules. This novel
      molecule was generated by replacing the DNA sequences encoding the alpha helices
      of the Ld gene with the corresponding sequences from the Kb gene. Serologic
      analysis of transfected L cells that expressed the chimeric molecule (Kb alpha Ld
      beta) revealed that the engineered class I glycoprotein retains two
      conformational epitopes associated with the alpha helices of Kb, as defined by
      monoclonal antibodies K10.56 and 28-13-3. These results demonstrate that the
      alpha helices of Kb can associate with the beta-pleated sheets of Ld to form a
      stable structure, which is expressed on the cell surface. To address the role of
      the alpha helices of the ARS in determining T cell crossreactivity, alloreactive
      cytotoxic T lymphocytes (CTL) were used to analyze L cells expressing Kb alpha Ld
      beta. CTL raised against Kb or Ld as alloantigens showed little, if any, ability
      to lyse L cells expressing Kb alpha Ld beta. Thus, alloreactive CTL did not
      recognize structures determined by the alpha helices alone or by the beta sheets
      of the ARS alone. However, bulk and cloned alloreactive CTL that were generated
      against the mutant Kb glycoprotein Kbm8 reacted strongly with Kb alpha Ld beta.
      In addition to the Kb alpha helices, the Kbm8 ARS shares a single polymorphic
      amino acid at position 24 with Kb alpha Ld beta. Amino acid 24 is located on the
      beta 2 strand that forms part of the floor of the ARS and has been identified as
      a component of pocket B in the HLA class I ARS. The substitution of Glu to Ser at
      this position was shown previously to be the central determinant of the Kbm8
      mutant alloantigenicity. The functional significance of this position in
      determining crossreactivity between bm8 and Kb alpha Ld beta identifies pocket B
      as a strong anchor for allogenic self-peptides. These findings demonstrate that
      determinants recognized by CTL on class I alloantigens are formed by interactions
      involving both the alpha helices and beta sheets of the ARS. These interactions
      are best explained by the influence of the alpha helices and beta sheets on the
      peptide-binding properties of these antigen-presenting molecules.

PMID- 1371307
TI  - Calmodulin activation of the Ca2+ pump revealed by fluorescent chelator dyes in
      human red blood cell ghosts.
AB  - Ca2+ transport in red blood cell ghosts was monitored with fura2 or quin2
      incorporated as the free acid during resealing. This is the first report of
      active transport monitored by the fluorescent intensity of the chelator dyes
      fura2 (5-50 microM) or quin2 (250 microM) in hemoglobin-depleted ghosts. Since
      there are no intracellular compartments in ghosts and the intracellular
      concentrations of all assay chelator substances including calmodulin (CaM), the
      dyes, and ATP could be set, the intracellular concentrations of free and total Ca
      [( Cafree]i and [Catotal]i) could be calculated during the transport. Ghosts
      prepared with or without CaM rapidly extruded Ca2+ to a steady-state
      concentration of 60-100 nM. A 10(4)-fold gradient for Ca2+ was routinely produced
      in medium containing 1 mM Ca2+. During active Ca2+ extrusion, d[Cafree]i/dt was a
      second order function of [Cafree]i and was independent of the dye concentration,
      whereas d[Catotal]i/dt increased as a first order function of both the [Cafree]i
      and the concentration of the Ca:dye complex. CaM (5 microM) increased
      d[Catotal]i/dt by 400% at 1 microM [Cafree]i, while d[Cafree]i/dt increased by
      only 25%. From a series of experiments we conclude that chelated forms of Ca2+
      serve as substrates for the pump under permissive control of the [Cafree]i, and
      this dual effect may explain cooperativity. Free Ca2+ is extruded, and probably
      also Ca2+ bound to CaM or other chelators, while CaM and the chelators are
      retained in the cell.

PMID- 1371308
TI  - Ca(2+)-activated K+ channels in human leukemic T cells.
AB  - Using the patch-clamp technique, we have identified two types of Ca(2+)-activated
      K+ (K(Ca)) channels in the human leukemic T cell line. Jurkat. Substances that
      elevate the intracellular Ca2+ concentration ([Ca2+]i), such as ionomycin or the
      mitogenic lectin phytohemagglutinin (PHA), as well as whole-cell dialysis with
      pipette solutions containing elevated [Ca2+]i, activate a voltage-independent K+
      conductance. Unlike the voltage-gated (type n) K+ channels in these cells, the
      majority of K(Ca) channels are insensitive to block by charybdotoxin (CTX) or 4
      aminopyridine (4-AP), but are highly sensitive to block by apamin (Kd less than 1
      nM). Channel activity is strongly dependent on [Ca2+]i, suggesting that multiple
      Ca2+ binding sites may be involved in channel opening. The Ca2+ concentration at
      which half of the channels are activated is 400 nM. These channels show little
      voltage dependence over a potential range of -100 to 0 mV and have a unitary
      conductance of 4-7 pS in symmetrical 170 mM K+. In the presence of 10 nM apamin,
      a less prevalent type of K(Ca) channel with a unitary conductance of 40-60 pS can
      be observed. These larger-conductance channels are sensitive to block by CTX.
      Pharmacological blockade of K(Ca) channels and voltage-gated type n channels
      inhibits oscillatory Ca2+ signaling triggered by PHA. These results suggest that
      K(Ca) channels play a supporting role during T cell activation by sustaining
      dynamic patterns of Ca2+ signaling.

PMID- 1371310
TI  - Distribution of the blood-brain barrier in heterotopic brain transplants and its
      relationship to the lesions of EAE.
AB  - The blood-brain barrier (BBB) is recognized as a barrier to the trafficking of
      molecules and cellular elements into the central nervous system (CNS).
      Horseradish peroxidase (HRP) exclusion is used as a measure of BBB integrity. The
      BBB is altered and becomes permeable during the course of experimental allergic
      encephalomyelitis (EAE). Heterotopic brain transplantation into the anterior eye
      chamber is a technique for studying genetic influences and the role of individual
      cell types on the development of EAE. Prior to EAE induction, HRP is excluded
      from the central portion of the transplant, demonstrating an intact BBB. In
      contrast, HRP localization is found at the periphery of the transplant,
      suggesting an incomplete barrier. However, EAE lesions typically occur within the
      more central regions of the transplant, where the BBB is intact, and not at
      peripherally located "leaky" areas. This suggests that endothelial cells at
      intact BBB sites may direct trafficking of lymphocytes (gating) into the CNS
      during the development of EAE, rather than the passive entry of lymphocytes into
      the CNS through a leaky BBB.

PMID- 1371309
TI  - Sustained and transient calcium currents in horizontal cells of the white bass
      retina.
AB  - Calcium currents were recorded from cultured horizontal cells (HCs) isolated from
      adult white bass retinas, using the whole-cell patch-clamp technique. Ca2+
      currents were enhanced using 10 mM extracellular Ca2+, while Na+ and K+ currents
      were pharmacologically suppressed. Two components of the Ca2+ current, one
      transient, the other sustained, were found. The large transient component of the
      Ca2+ current, which has not been seen before in HCs, is similar, but not
      identical, to the T-type Ca2+ current described previously in a variety of
      preparations. The sustained component of the Ca2+ current is similar, but not
      identical, to the L-type current described in other preparations. FTX, a factor
      isolated from the venom of the funnel-web spider, Agelenopsis aperta,
      preferentially and irreversibly blocks the sustained component of the Ca2+
      current at very dilute concentrations. The sustained component of the Ca2+
      current inactivates slowly, over the course of 15-60 s, in some HCs. This
      inactivation of the sustained Ca2+ current, when present, is primarily voltage
      dependent rather than Ca2+ dependent.

PMID- 1371311
TI  - Regional differentiation of the human fetal ependyma: immunocytochemical markers.
AB  - The development of the ependyma from 6 weeks (wk) gestation to term was studied
      in 26 human fetuses and infants for immunocytochemical differentiation using
      antibodies against vimentin, several cytokeratins, glial fibrillary acidic
      protein (GFAP) and S-100 protein. Acridine orange-RNA fluorescence was uniform in
      all differentiated ependymal cells. Marked differences were demonstrated among
      various anticytokeratin antibodies. Vimentin was demonstrated in undifferentiated
      cells, particularly during mitosis, and persisted as the ependyma matured. It was
      strong in floor plate cells and processes forming the ventral median septum.
      Vimentin and cytokeratin CK-904 coexisted with other immunoreactive proteins but
      disappeared in a caudorostral gradient with maturation. At 8 wk gestation, GFAP
      was detected in roof plate cells and their processes forming the dorsal median
      septum. S-100 protein appeared as early as 6 wk and had a more restricted
      regional distribution than GFAP at all ages. It was strong in the basal plate
      ependyma of the spinal cord in young fetuses. The temporal and spatial
      distributions of the immunoreactive proteins studied correlate with evidence that
      fetal ependymal cells synthesize compounds that attract or repel axonal growth
      cones to prevent axons from entering the ventricles or deviating from programmed
      projection pathways. An additional role may be to induce the transformation of
      radial glial cells in the subventricular zone.

PMID- 1371312
TI  - Activity-dependent fluorescent staining and destaining of living vertebrate motor
      nerve terminals.
AB  - Living motor nerve terminals from several species can be stained in an activity
      dependent fashion by certain styryl dyes, such as RH414, RH795, and a new dye,
      FM1-43, which can be imaged independently of the others. The dyes evidently
      become trapped within recycled synaptic vesicles. In frog cutaneus pectoris
      muscle, bright fluorescent spots spaced regularly along the length of the nerve
      terminals appear after stimulation in the presence of the dye. The spots align
      well with postsynaptic ACh receptors and are persistent for many hours, unless
      further stimulation is given, in which case the spots disappear. Destaining, like
      staining, requires transmitter release and proceeds gradually over several
      minutes at high stimulus frequencies (e.g., 30 Hz), and fluorescent spots in the
      same terminal disappear at about the same rate. We suggest that each spot is a
      cluster of hundred of synaptic vesicles and that the mechanism of staining
      involves the ability of the dyes to partition reversibly into the outer leaflet
      of surface membranes, without being able to penetrate the entire membrane
      thickness. Then, during endocytosis following transmitter release, dye molecules
      become trapped in recycled synaptic vesicle membranes. The dyes therefore make it
      possible optically to study vesicle exocytosis and recycling in living nerve
      terminals in real time, and should be useful for marking terminals in a variety
      of preparations according to their level of activity.

PMID- 1371313
TI  - Axonogenesis and morphogenesis in the embryonic zebrafish brain.
AB  - We have examined early neuronal differentiation and axonogenesis in the fore- and
      midbrain of zebrafish embryos to address general issues of early vertebrate brain
      development. AChE expression and HNK-1 antibody immunoreactivity were used as
      markers for differentiated neurons and axons, respectively. The pattern of
      neuronal differentiation followed a stereotyped sequence. AChE-positive cells
      first appeared between 14 and 16 hr in three small, isolated, bilaterally
      symmetrical clusters on the surface of the brain. The three clusters--the
      dorsorostral, ventrorostral, and ventrocaudal clusters--proved to be the
      progenitors of the telencephalon, ventral diencephalon, and mesencephalic
      tegmentum, respectively. With further development, more cells were added to these
      three clusters, and new clusters appeared in the anlage of the epiphysis (18 hr)
      and in the pituitary and dorsal mesencephalon (by 24 hr). Subsequently, as more
      neurons differentiated, the gaps of unlabeled cells were reduced; by 48 hr, the
      cluster boundaries were indistinguishable. Axonogenesis also followed a
      stereotyped sequence. The first HNK-1-labeled processes arose from the first
      three clusters of AChE-positive cells and connected the clusters. The earliest
      axonal growth cones appeared at 16 hr, directed caudally from two to three
      neurons of the ventrocaudal cluster and pioneering the ventral longitudinal
      tract. By 18 hr, the tract of the postoptic commissure was initiated by growth
      cones directed caudally from the ventrorostral cluster toward the ventrocaudal
      cluster. By 20 hr, axons from the dorsorostral cluster projected ventrally to
      form the supraoptic tract. The other dorsoventral tracts (the dorsoventral
      diencephalic tract and the tract of the posterior commissure) became evident
      between 20 and 24 hr. These observations provide a continuous record of the
      topological distortions involved in the conversion of the tubular embryonic brain
      into the contorted adult form. The telencephalon, ventral diencephalon, and
      hypothalamus originate from the same rostrocaudal level of the neural tube. The
      pattern of differentiation demonstrated that the early development of the rostral
      neural tube occurs simultaneously in several independent centers, similar to the
      overtly segmental development of the hindbrain.

PMID- 1371314
TI  - Development of axonal arbors of layer 4 spiny neurons in cat striate cortex.
AB  - Spiny neurons in layer 4 of cat striate cortex are the primary recipients of
      geniculocortical afferents and provide crucial links to other cortical layers for
      processing visual information. Using intracellular staining, we examined the
      development of the local axonal projections of these neurons to determine (1)
      whether the laminar specificity of their projections emerged specifically or was
      sculpted from transient exuberant projections and (2) whether the emergence of
      excitatory connections from layer 4 to layer 2/3 could contribute to the activity
      dependent development of clustered horizontal connections of layer 2/3 pyramidal
      neurons. Differences in the extent of projections to infragranular (layers 5 and
      6, which receive sparse projections) versus superficial layers (layers 2/3 and 4,
      which receive extensive projections) developed specifically from the outset. By
      postnatal day 15 (P15) projections to infragranular layers matured and were
      indistinguishable from those in the oldest animal studied (P33). In contrast,
      projections to superficial layers continued to increase in complexity after P15.
      Projections within layer 4, which were the most elaborate at all ages studied,
      reached maturity at about P20, while those to layer 2/3 continued to increase in
      complexity through P33. No evidence for exuberant projections to any of these
      cortical layers was observed. At very early postnatal ages (P5) projections to
      the subplate region were evident. These disappeared by P8-P11, suggesting the
      presence of transient connections from layer 4 spiny neurons to subplate neurons.
      Binocular deprivation did not prevent the emergence of projections from layer 4
      spiny neurons into layer 2/3 or development of normal laminar differences in
      projection density. Connections from layer 4 to layer 2/3 emerged after
      horizontal connections in layer 2/3 were crudely clustered, but in synchrony with
      the later refinement of clusters. Collaterals from layer 4 cells first crossed
      into layer 3 at P11, but were extremely short (extending only 50-200 microns
      beyond the laminar boundary) and uncommon (only 4 of 19 cells). Since by P8
      horizontal projections of layer 2/3 pyramidal neurons are already crudely
      clustered, the emergence of crude clustering is probably independent of layer 4
      to layer 2/3 excitatory projections. The proportion of cells projecting to layer
      2/3 and the complexity of their arbors both increased in the subsequent weeks,
      closely matching the timing of both the refinement of crudely clustered
      horizontal connections and the emergence of visual responsiveness in layer
      2/3.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1371315
TI  - Activation and desensitization of AMPA/kainate receptors by novel derivatives of
      willardiine.
AB  - Willardiine [(S)-1-(2-amino-2-carboxyethyl)pyrimidine-2,4-dione] is a naturally
      occurring heterocyclic excitatory amino acid present in the seeds of Acacia and
      Mimosa. A series of 5-substituted willardiines were synthesized in single
      enantiomeric forms and tested for activity at AMPA/kainate receptors, using whole
      cell recording from mouse embryonic hippocampal neurons. The (S)- but not (R)
      isomers of willardiine and 5-bromowillardiine were potent agonists, producing
      rapidly but incompletely desensitizing responses. At equilibrium, (S)-5
      fluorowillardiine (EC50, 1.5 microM) was seven times more potent than (R,S)-AMPA
      (EC50, 11 microM) and 30 times more potent than willardiine (EC50, 45 microM);
      the potency sequence was fluoro greater than nitro greater than chloro
      approximately bromo greater than iodo greater than willardiine. Willardiines
      produce strikingly different degrees of desensitization: at saturating doses the
      equilibrium response to the weakly desensitizing agonist (S)-5-iodowillardiine
      was similar in amplitude to the response to kainate and 10 times larger than the
      response to the strongly desensitizing agonist (S)-willardiine. The
      desensitization sequence was fluoro greater than willardiine greater than nitro
      approximately chloro greater than bromo greater than iodo greater than kainate.
      Cross-desensitization experiments confirm that willardiines bind to the same
      receptors activated by kainate and AMPA, and show that both the rapidly
      desensitizing and equilibrium responses to willardiines are mediated by the same
      receptor: (S)-5-iodowillardiine blocked activation of the rapidly desensitizing
      response evoked by (S)-willardiine and (S)-5-fluorowillardiine, while the latter
      agonists blocked the equilibrium response to (S)-5-iodowillardiine. A slowly
      decaying inward tail current was recorded after a brief application of (S)-5
      fluorowillardiine but not (S)-willardiine, consistent with a model in which
      willardiines bind with different affinity to desensitized receptors, such that
      following removal of agonist, receptors trapped in the desensitized state can
      return to the open state before dissociation of agonist terminates receptor
      activation. Willardiines are the first compounds characterized in which simple
      changes in molecular structure are associated with marked differences in the
      ability of agonists to produce desensitization of AMPA/kainate receptors.

PMID- 1371316
TI  - Synaptic plasticity in Drosophila memory and hyperexcitable mutants: role of cAMP
      cascade.
AB  - Activity-dependent synaptic plasticity has been implicated in the refinement and
      modification of neural circuits during development and learning. Previous studies
      show that activity-induced facilitation and potentiation are disrupted at larval
      neuromuscular junctions in the memory mutants dunce (dnc) and rutabaga (rut) of
      Drosophila. The diminished learning-memory capacity and synaptic transmission
      plasticity have been associated with altered cAMP levels since dnc affects the
      cAMP-specific phosphodiesterase and rut affects adenylate cyclase. In this study,
      the morphology of larval motor axon terminals was examined by anti-HRP
      immunohistochemistry. It was found that the numbers of terminal varicosities and
      branches were increased in dnc mutants, which have elevated cAMP concentrations.
      Such increase was suppressed in dnc rut double mutants by rut mutations, which
      reduce cAMP synthesis. More profuse projections of larval motor axons have also
      been reported in double-mutant combinations of ether a go-go (eag) and Shaker
      (Sh) alleles, which display greatly enhanced nerve activity as a result of
      reduction in different K+ currents. Therefore, we examined combinations of dnc
      and rut with eag and Sh mutations to explore the possible relation between
      activity- and cAMP-induced morphological changes. We found that the expanded
      projections in dnc were further enhanced in double mutants of dnc with either eag
      or Sh, an effect that could again be suppressed by rut. The results provide
      evidence for altered plasticity of synaptic morphology in memory mutants dnc and
      rut and suggest a role of cAMP cascade in mediating activity-dependent synaptic
      plasticity.

PMID- 1371317
TI  - Transmitter-operated channels in rabbit retinal astrocytes studied in situ by
      whole-cell patch clamping.
AB  - Glutamate and GABA open ion channels in the membranes of astrocytes found on the
      vitreal surface of the rabbit retinal visual streak. The glutamate-operated
      channels are opened by kainate, quisqualate, and AMPA, but not by NMDA,
      aspartate, or the metabotropic agonist 1-aminocyclopentane-1 S,3R-dicarboxylic
      acid. The effects of glutamate and its analogs can be blocked by 20 microM 6
      cyano-7-nitroquinoxaline-2,3-dione. The conductance increase evoked by 10 microM
      glutamate, a concentration of this transmitter near to that found in the vitreous
      humor that bathes these cells, was equivalent to 22% of the cell's resting
      conductance. The conductance increase evoked by 1 microM GABA, a concentration
      near that found in the vitreous, was equivalent to 131% of the cell's resting
      conductance. The effects of GABA can be blocked by bicuculline. These data show
      that GABA, and non-NMDA-type glutamate receptors play an important part in
      determining the resting potential of visual streak astrocytes in situ and that
      these channels may be of general importance for the functions of astrocytes in
      vivo.

PMID- 1371318
TI  - The effects of pulsed electromagnetic fields on blood vessel growth in the rabbit
      ear chamber.
AB  - A double-blind, controlled trial of the effects of pulsed electromagnetic fields
      on capillary growth in the rabbit ear chamber in adult New Zealand white rabbits
      has been performed. Three waveforms have been investigated. The first, a pulse
      burst waveform, produced a significant increase in the rate of growth of the
      vascular tissue within the chamber, but had no effect on macroscopic tissue
      maturation. The second and third, two different single pulse waveforms, had, in
      contrast, no significant effect on the rate of vascular growth and only an effect
      on vessel characteristics, with increased maturation of vessels using the second
      waveform. It is concluded that some of the observed effects of pulsed
      electromagnetic fields on tissue healing may be mediated through a primary effect
      on vascular growth.

PMID- 1371319
TI  - Type- and group-specific continuous antigenic determinants of HTLV. Use of
      synthetic peptides for serotyping of HTLV-I and -II infection.
AB  - The human T lymphotropic viruses (HTLV-I and -II) are relatively common in
      subpopulations of certain countries, notably intravenous drug abusers in North
      America. Infections with these malignancy-associated human retroviruses are hard
      to discriminate with currently available commercial serological tests. We studied
      the distribution of antigenicity and the degree of cross-reactivity of epitopes
      in gag and env of the two viruses. Sequences in the carboxyl terminus of the
      matrix protein (MA) and the middle of the outer glycoprotein (SU) reacted in a
      type-specific fashion, while sequences from the capsid protein (CA), the carboxyl
      terminus of SU, and conserved portions of the transmembrane protein (TM) mainly
      reacted in a group-specific fashion, correlating with the degree of sequence
      dissimilarity between the two viruses. The serological discrimination obtained
      with the peptides was evaluated in a panel of 25 sera where infection with HTLV-I
      or -II had been typed by competition in a p24 enzyme-linked immunosorbent assay
      (ELISA) or by the polymerase chain reaction (PCR). After processing peptide
      results in a computer program, a typing result concordant with earlier results
      was obtained in 21 of 25 sera. Of the remaining five sera, four were labeled "too
      weak for typing" and one "HTLV of uncertain type" by the program. They did not
      react sufficiently strongly or clearly with the peptides to allow classification.
      A combination of synthetic peptides may become useful for serotyping HTLV
      infection and become an alternative to Western blots for confirmation of HTLV
      positivity.

PMID- 1371320
TI  - Isolation of haemin-binding proteins of Neisseria gonorrhoeae.
AB  - Although Neisseria gonorrhoeae can use haem as the sole exogenous iron source for
      growth in vitro, the mechanism of haem-iron uptake in the gonococcus is unknown.
      Two haemin-binding proteins (HmBPs) of 97 and 44 Kda were isolated by batch
      ligand affinity-chromatography from whole cells or total membranes of gonococci
      grown under iron-limited conditions but not from those grown under iron
      sufficient conditions. Competition binding experiments indicated that the haemin
      protein interaction was specific; only haemin or haem-containing proteins, such
      as human haemoglobin or equine cytochrome c111, but not protoporphyrin IX, iron
      loaded human transferrin or lactoferrin, could abrogate binding. Identical HmBPs
      were isolated from three other clinical gonococcal strains, suggesting that these
      may be interstrain structural and functional homogeneity amongst these
      polypeptides.

PMID- 1371321
TI  - The effects of burn injury on the acute phase response.
AB  - The time course of changes in the levels of acute-phase-reactant (APR) mRNAs in
      different tissues of rats with a 10% or a 60% total-body-surface-area (TBSA) burn
      and the relationship between the induction of APRs and the host's tolerance to
      thermal injury were studied. The acute phase response in a LPS-induced
      inflammation model and a burn-plus-LPS model were compared. The results of this
      study indicated that (1) the major site of APR synthesis is the liver; (2) even a
      small surface burn injury can elicit a rapid acute phase response, but the
      intensity of APR expression increases with the severity of the burn; (3) the down
      regulation of albumin mRNA, which is characteristic of the acute phase response,
      does not occur even though transferrin (Trf) mRNA levels are significantly
      decreased; (4) the resistant strain of inbred rats showed higher levels of alpha
      1-antitrypsin (AT) mRNA before and after burn injury, indicating its contribution
      to the host's tolerance to thermal injury; (5) the increases in alpha 1-acid
      glycoprotein (AGP) and AT expressions are limited in the burn-plus-LPS rat model
      compared with either the burn model or LPS-stimulated model alone.

PMID- 1371322
TI  - From the Centers for Disease Control. Update: cholera--western hemisphere, 1991.

PMID- 1371323
TI  - Endogenous interferon and triglyceride concentrations to assess response to
      zidovudine in AIDS and advanced AIDS-related complex.
AB  - To improve evaluation of new antiretroviral drugs in the acquired
      immunodeficiency syndrome (AIDS), sensitive biological markers that accurately
      predict response to treatment are needed. Two possible markers are endogenous
      interferon (E-IFN), which is a cytokine involved in the pathophysiology of AIDS,
      and serum triglycerides (TG), which are raised in patients with AIDS, possibly
      reflecting enhanced cytokine activity. E-IFN, TG, body-mass index, CD4 count, and
      HIV p24 were measured in 19 patients (15 with AIDS, 4 with AIDS-related complex),
      who were part of the phase II licensing trial of zidovudine (ZDV). 10 received
      ZDV and 9 received placebo. Rapid, significant, and sustained declines from
      initial values in E-IFN and TG concentrations were observed in ZDV patients but
      not in placebo patients. Baseline values of E-IFN and TG concentrations after 4
      months on ZDV treatment were both important contributors to long-term survival.
      The findings suggest that these indicators of abnormal cytokine expression may be
      useful measures of not only disease severity but also efficacy of antiretroviral
      therapy in AIDS.

PMID- 1371325
TI  - Dosage of thiacetazone.

PMID- 1371324
TI  - Failure to detect cytomegalovirus DNA in pancreas in type 2 diabetes.
AB  - We have attempted to confirm the finding of cytomegalovirus (CMV) nucleic acid
      sequences in pancreas sections from patients with type 2 diabetes in a large
      population since this finding has major implications for the pathogenesis of the
      disorder. A highly sensitive nested polymerase chain reaction method was
      developed to detect the immediate-early CMV gene in DNA extracted from wax
      embedded tissue sections. We could not confirm the previous findings; CMV DNA was
      not detected in pancreas sections from 43 type 2 diabetic patients or from 38 non
      diabetic age-matched subjects, although the method detected CMV DNA, even in very
      low concentrations, in positive controls.

PMID- 1371326
TI  - The effect of some new platinum (II) and palladium (II) coordination complexes on
      rat hepatic nuclear transcription in vitro.
AB  - Several new L-amino acid derivatives of 2,2'-bipyridine and 1,10-phenanthroline
      complexes of platinum (Pt) and palladium (Pd) and a few binuclear 2,2'-bipyridine
      complexes of these metals were tested for their potential to inhibit rat hepatic
      nuclear transcription in vitro. Pd complexes were generally more effective
      inhibitors of transcription than the corresponding Pt complexes. Among Pd-diimine
      chlorides, the 2,2'-bipyridine complex was nearly 10 times more active than the
      corresponding 1,10-phenanthroline complex. Both Pt-diimine chlorides, however,
      showed same level of inhibitory activity. Amino acid derivatives were less
      inhibitory with respect to the parent metal diimine chlorides except for 1,10
      phenanthroline complexes of Pd. For binuclear 2,2'-bipyridine complexes of Pt,
      the increase in length of linking hydrocarcon chain increased the inhibitory
      potential of the complex. The mechanism of inhibition of transcription by these
      metal complexes was sought to be understood by use of actinomycin-D and poly[d(I
      C)] to differentiate effect on the two major components of transcription
      machinery viz. the template and the enzyme. These studies along with studies on
      reconstituted system of transcription using either pretreated template or enzyme
      indicate that these metal complexes displayed dual effect on transcription by
      inhibiting both the template and the enzymes.

PMID- 1371327
TI  - Cloning of a 21.7-kDa vaccine-dominant antigen gene of Schistosoma mansoni
      reveals an EF hand-like motif.
AB  - Several cDNA clones encoding a 21.7-kDa antigen (Sm21.7) were detected from a
      Schistosoma mansoni sporocyst cDNA expression library using irradiated cercaria
      vaccinated rabbit serum. The antigen was designated 'vaccine dominant' because
      parasite-derived Sm21.7 was recognised preferentially by mouse vaccine sera
      compared with mouse infection sera. The cDNA and corresponding gDNA sequences
      showed 64% identity at the nucleotide level and 47% identity at the amino acid
      level with the sequence of a previously described S. mansoni tegumental antigen,
      sma22.6. Whereas sma22.6 mRNA occurs almost exclusively in the adult worm, Sm21.7
      mRNA was equally abundant in the sporocyst, schistosomular and adult stages. Both
      Sm21.7 and sma22.6 sequences reveal a motif strongly homologous to the EF hand
      calcium binding domain but lacking the invariant glycine in the calcium binding
      loop. The disruptive nature of the glutamine which in Sm21.7 replaces the glycine
      explains why the motif is non-functional, as shown by the inability of Sm21.7 to
      bind calcium.

PMID- 1371328
TI  - Some kinetic properties of pyruvate kinase from Trypanosoma brucei.
AB  - We have studied the kinetics of the allosteric interactions of pyruvate kinase
      from Trypanosoma brucei. The kinetics for phosphoenolpyruvate depended strongly
      on the nature of the bivalent metal ions. Pyruvate kinase activated by Mg2+ had
      the highest catalytic activity, but also the highest S0.5 for
      phosphoenolpyruvate, while the opposite was true for pyruvate kinase activated by
      Mn2+. The reaction rates of Mg(2+)-pyruvate kinase and Mn(2+)-pyruvate kinase
      were clearly allosteric with respect to phosphoenolpyruvate, while the kinetics
      with Co(2+)-pyruvate kinase were hyperbolic. However, Co(2+)-pyruvate kinase was
      still sensitive to heterotropic activation. Trypanosomal pyruvate kinase is
      unique in that the best activator was fructose 2,6-bisphosphate. Ribulose 1,5
      bisphosphate and 5-phosphorylribose 1-pyrophosphate were also strong heterotropic
      activators, which were much more effective than fructose 1,6-bisphosphate and
      glucose 1,6-bisphosphate. In the presence of the heterotropic activators, the
      sigmoidal kinetics with respect to phosphoenolpyruvate and the bivalent metal
      ions were modified as were the concentrations of phosphoenolpyruvate and the
      bivalent metal ions needed to attain the maximal activity. Maximal activities
      were not significantly changed with Mg2+ and Mn2+ as the activating metal ions.
      Moreover, with Co2+ and fructose 2,6-bisphosphate or ribulose 1,5-bisphosphate or
      5-phosphorylribose 1-pyrophosphate, the maximal activity was significantly
      reduced. Ribulose 1,5-bisphosphate and 5-phosphorylribose 1-pyrophosphate
      resembled fructose 2,6-bisphosphate rather than fructose 1,6-bisphosphate and
      glucose 1,6-bisphosphate in their action in that the K0.5 values for the former 3
      compounds increased when Mg2+ was replaced by Co2+, while the K0.5 for fructose
      1,6-bisphosphate and glucose 1,6-bisphosphate increased.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1371329
TI  - Structure and expression of the gene for Pv200, a major blood-stage surface
      antigen of Plasmodium vivax.
AB  - Molecular cloning and structure analysis of the gene encoding the Pv200 protein
      of the Sal-1 strain of Plasmodium vivax revealed an overall identity of 34-37%
      when the deduced amino acid sequence was compared with the sequences of various
      major merozoite surface antigens of Plasmodium falciparum, Plasmodium yoelii and
      Plasmodium chabaudi. When the Sal-1 Pv200 sequence was compared with the
      corresponding sequence from the Belem strain of P. vivax, it was found that the
      two merozoite surface antigens were relatively well conserved with an overall
      amino acid sequence identity of 81%. A region of 23 repeated glutamine residues,
      found in the sequence of the Belem isolate was not found, however, in the Sal-1
      sequence. Amino- and carboxy-terminal domains of the Pv200 protein were expressed
      in the yeast Saccharomyces cerevisiae. Each recombinant protein was shown to
      react with antibodies in sera from splenectomized Bolivian Saimiri monkeys that
      had been infected previously with P. vivax, and in human sera from individuals
      with a history of exposure to vivax malaria. The availability of recombinant DNA
      derived Pv200 proteins will now allow a full assessment of their utility in the
      diagnosis and immunoprophylaxis of the benign tertian malaria associated with P.
      vivax infection.

PMID- 1371330
TI  - Potentiation of NMDA receptor currents by arachidonic acid.
AB  - Arachidonic acid is released by phospholipase A2 when activation of N-methyl-D
      aspartate (NMDA) receptors by neurotransmitter glutamate raises the calcium
      concentration in neurons, for example during the initiation of long-term
      potentiation and during brain anoxia. Here we investigate the effect of
      arachidonic acid on glutamate-gated ion channels by whole-cell clamping isolated
      cerebellar granule cells. Arachidonic acid potentiates, and makes more transient,
      the current through NMDA receptor channels, and slightly reduces the current
      through non-NMDA receptor channels. Potentiation of the NMDA receptor current
      results from an increase in channel open probability, with no change in open
      channel current. We observe potentiation even with saturating levels of agonist
      at the glutamate- and glycine-binding sites on these channels; it does not result
      from conversion of arachidonic acid to lipoxygenase or cyclooxygenase
      derivatives, or from activation of protein kinase C. Arachidonic acid may act by
      binding to a site on the NMDA receptor, or by modifying the receptor's lipid
      environment. Our results suggest that arachidonic acid released by activation of
      NMDA (or other) receptors will potentiate NMDA receptor currents, and thus
      amplify increases in intracellular calcium concentration caused by glutamate.
      This may explain why inhibition of phospholipase A2 blocks the induction of long
      term potentiation.

PMID- 1371331
TI  - Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm.
AB  - RNA polymerase II transcripts, heterogeneous nuclear RNAs (hnRNAs), associate in
      the nucleus with specific proteins that bind premessenger RNA (hnRNP proteins)
      and with small nuclear ribonucleoprotein particles (snRNPs). These hnRNA-hnRNP
      snRNP complexes assemble on nascent transcripts and hnRNA is processed to mRNA in
      them. HnRNP proteins have been localized to the nucleoplasm and their functions
      were presumed to be limited to nuclear events in mRNA biogenesis. It was proposed
      that an exchange of hnRNP for mRNA-binding proteins accompanies transport of mRNA
      from the nucleus to the cytoplasm. We show here that several of the abundant
      hnRNP proteins, including A1, shuttle between the nucleus and the cytoplasm.
      HnRNP proteins may thus also have cytoplasmic functions. Furthermore, when in the
      cytoplasm, A1 is bound to mRNA and RNA polymerase II transcription is necessary
      before it can return to the nucleus. We propose that the cytoplasmic
      ribonucleoprotein complex of mRNA with hnRNP proteins is the substrate of nuclear
      cytoplasmic transport of mRNA.

PMID- 1371332
TI  - Limitations of image enhancement for the visually impaired.
AB  - Image enhancement as an aid for the visually impaired may improve visibility of
      TV programs and provide portable visual aid. This paper describes the current
      techniques for image enhancement and their underlying models. The limitations of
      the various techniques and of potential methods of implementation are high
      lighted. Initial work in this area was based on a linear model. The finite
      dynamic range available in the video display and contamination of the enhanced
      image by high spatial frequency noise limited the model's usefulness. I propose a
      method to address some limitations of the original model that considers the
      nonlinear response of the visual system and requires enhancement of subthreshold
      spatial information only. This modification may increase the dynamic range
      available by decreasing the range previously used by the linear models to enhance
      visible details. However, for the modified technique to be most effective, the
      enhancement has to be continuously tuned, based on the patient's visual loss and
      the spatial frequency content of the displayed images. The implications of these
      limitations for the potential implementation in TV are discussed. Implementation
      of an image-enhancing visual aid in a head-mounted, binocular, full-field,
      virtual vision device may cause substantial difficulties. Patient adaptation may
      be difficult due to head movement and interaction of the vestibular system
      response with the head-mounted display. An alternate, bioptic design is proposed
      in which the display is positioned above or below the line of sight to be
      examined intermittently, possibly in a freeze-frame mode. Such implementation is
      also likely to be less expensive, enabling more users access to the device.

PMID- 1371333
TI  - Challenges in applying autofocus technology to low vision telescopes.
AB  - Autofocus (AF) low vision telescopes offer the potential to increase the
      acceptance and utilization of such low vision aids (LVA) by the visually
      impaired. Many patients resist conventional manual focus telescopes for a variety
      of reasons including appearance, field of view, weight, and utility. The elderly
      who comprise the significant part of the target population may also resist
      telescopes due to an avoidance of the technical challenge of its use. Although an
      AF telescope is technically advanced, it may allow for less manipulation by the
      wearer and hence enable its more effective application to visual tasks,
      especially in the near- to mid-range where depths of field narrow and the demands
      for focusing increase. There are many challenges involved in the application of
      AF technology to LVA including modification of the focusing range, signal
      processing for physiologically acceptable performance, and power and weight
      considerations. A preliminary infrared (IR) AF prototype based upon our recent
      work with the Ocutech Vision Enhancing System (VES) has been produced. Initial
      findings are presented which address the requirements of a subsequent version as
      well as the challenges that will be faced to optimize such a device.

PMID- 1371334
TI  - Obstacles encountered in the development of the low vision enhancement system.
AB  - The Johns Hopkins Wilmer Eye Institute and the NASA Stennis Space Center are
      collaborating on the development of a new high technology low vision aid called
      the Low Vision Enhancement System (LVES). The LVES consists of a binocular head
      mounted video display system, video cameras mounted on the head-mounted display,
      and real-time video image processing in a system package that is battery powered
      and portable. Through a phased development approach, several generations of the
      LVES can be made available to the patient in a timely fashion. This paper
      describes the LVES project with major emphasis on technical problems encountered
      or anticipated during the development process.

PMID- 1371335
TI  - The immediate early gene response to a differentiative stimulus is disrupted by
      the v-abl and v-ras oncogenes.
AB  - The immediate early gene activation in response to a differentiative stimulus was
      investigated in the hematopoietic progenitor cell line 32DC13(G). A transient and
      coordinated increase in mRNA levels for c-fos, c-jun, jun-B, TIS-7/PC-4, TIS
      8/egr-1, and TIS-11 occurred during the first 2 h of treatment with granulocyte
      colony stimulating factor (G-CSF), which ultimately induces the 32DC13(G) cells
      to terminally differentiate into neutrophilic granulocytes. This pattern of mRNA
      induction was disrupted by v-abl and v-ras, two oncogenes known to interfere with
      G-CSF-induced differentiation of 32DC13(G) cells. Induction of the mRNAs for c
      jun and TIS-7/PC-4 was blocked by the presence of v-abl, whereas v-ras caused
      constitutive expression of c-fos mRNA and blocked the c-jun, jun-B and TIS-7/PC-4
      mRNA response. Release of the differentiation block in the ras-transformed
      32DC13(G) cells by co-treatment with retinoic acid and G-CSF partially restored
      the normal c-fos and c-jun mRNA induction pattern, suggesting that the proper
      activation of these genes may be important for myeloid differentiation.

PMID- 1371336
TI  - The biochemical properties and transforming potential of human Wnt-2 are similar
      to Wnt-1.
AB  - Wnt-2 is a member of the Wnt gene family that includes the proto-oncogene Wnt-1
      (formerly Int-1). Although the predicted protein product of the Wnt-2 gene has
      only 38% amino acid identity with Wnt-1, it exhibits significant conservation of
      structural properties, including a hydrophobic signal sequence and invariant
      spacing and conservation of 22 cysteine residues. We have sought to characterize
      the biological and biochemical properties of Wnt family members and here present
      a characterization of Wnt-2 protein and a comparison with Wnt-1. We demonstrate,
      using both CHO and AtT-20 cells transfected with human Wnt-2 cDNA, that Wnt-2
      encodes a 33 kDa protein that is modified by N-linked glycosylation to a 35 kDa
      species. Secreted Wnt-2 protein was detected in the culture medium only after
      cells were treated with suramin indicating that, like Wnt-1 protein, Wnt-2 is
      tightly associated with the cell surface. Expression of Wnt-2 cDNA in the mammary
      epithelial cell line C57 mg results in loss of density-inhibited growth and
      induces a transformed phenotype in monolayer culture similar to the effects
      produced by Wnt-1. These results indicate that Wnt-2 shares several biochemical
      and biological characteristics with Wnt-1 and suggests that other Wnt family
      members, by virtue of conserved structural features, may also exhibit similar
      properties.

PMID- 1371337
TI  - Variable pattern of jun and fos gene expression in different hematopoietic cell
      lines during interleukin 3-induced entry into the cell cycle.
AB  - Jun (c-jun, jun-B and jun-D) and fos (c-fos, fos-B and fra) proteins dimerize to
      form the family of AP-1 transcriptional activators. If each dimer exhibits unique
      transactivating properties, then any phenotypic change should show a
      characteristic pattern of jun and fos expression. To test this hypothesis we have
      assessed jun and fos RNA expression after stimulation of the factor-dependent
      cell lines 32D and FDCP1. These hematopoietic progenitor lines become quiescent
      in G0/G1 after interleukin 3 (IL-3) deprivation, and upon stimulation
      synchronously enter the cell cycle. 32D cells respond to IL-3 with rapid
      induction of jun-B and c-fos, followed by induction of jun-D and fra-1, but no
      rise in c-jun expression. FDCP1 cells show a very different pattern, with
      induction of c-jun, jun-D and fra-1. To investigate the response of a single cell
      line to different physiological stimuli we used a 32D subclone engineered to
      respond to colony stimulating factor 1 (CSF-1). This subclone showed identical
      induction of jun and fos after stimulation with either CSF-1 or IL-3. The
      conservation of response of a single cell line, but the disparate patterns
      demonstrated by different cells, suggest a fundamental difference in both the
      regulation and function of the fos/jun complexes in these cells.

PMID- 1371338
TI  - Loss of c-kit expression in cultured melanoma cells.
AB  - The proto-oncogene c-kit encodes a receptor tyrosine kinase which has been shown
      to play a key role in melanocyte development. In this report we asked whether the
      c-kit gene product is also involved in promoting the growth of transformed
      melanocytes. We found that, while c-Kit protein was readily observed in normal
      human neonatal and adult melanocytes, the majority of cell lines established from
      human melanoma samples did not express detectable levels of c-kit mRNA or
      protein. A similar pattern of differential expression was also observed in normal
      and transformed murine melanocytes. Our findings raise the possibility that a
      marked reduction in c-kit gene expression either promotes or is a consequence of
      transformation in melanocytes.

PMID- 1371339
TI  - Interferon production during the course of Mycoplasma pneumoniae infection.
AB  - In patients infected with Mycoplasma pneumoniae the development of interferon
      (IFN) was studied in nasopharyngeal secretions and sera. The production of IFN
      gamma by lymphocytes was also investigated in response to M. pneumoniae antigen
      and mumps virus antigen. IFN-alpha was detected in 25 (61.0%) of 41
      nasopharyngeal secretion samples and in 25 (59.5%) of 42 serum samples within 6
      days after the onset of illness. IFN-alpha was significantly higher in
      nasopharyngeal secretions than in sera and a significant correlation was observed
      between the two. In most of the patients lymphocytes produced a larger amount of
      IFN-gamma in the convalescent stage than in the acute stage, when lymphocytes
      were stimulated with M. pneumoniae antigen. In some patients, however,
      lymphocytes did not produce IFN-gamma during the course of illness. Such
      lymphocytes, negative for IFN-gamma production in response to M. pneumoniae,
      produced IFN-gamma after the depletion of macrophages, and readdition of
      macrophages suppressed the production of IFN-gamma by lymphocytes. When
      lymphocytes were stimulated with heterogeneous antigen (mumps virus), they
      produced no IFN or a small amount of IFN in the acute stage of M. pneumoniae
      infection, and IFN production increased in the convalescent stage. Different
      mechanisms seem to work for homogeneous and heterogeneous antigens in the
      suppression of IFN production in M. pneumoniae infection.

PMID- 1371340
TI  - Hyperbilirubinemia in low birth weight infants and outcome at 5 years of age.
AB  - The collaborative national survey on morbidity and mortality in preterm and small
      for gestational age infants in the Netherlands enrolled initially 1338 infants
      born in 1983. The relationship between maximal serum total bilirubin
      concentration in the neonatal period and neurodevelopmental outcome in the
      survivors of this cohort was studied. This relationship at the corrected age of 2
      years was previously reported. A dose-response relationship between maximal serum
      total bilirubin concentration and risk of adverse outcome was observed in the 831
      surviving children. The present study reassessed the relationship at the age of 5
      years in 814 children. There was no significant difference in mean maximal serum
      total bilirubin concentration between the children with and without a handicap.
      This was confirmed by logistic regression analysis. After correction for seven
      suspected confounding factors (gestational age, birth weight, intracranial
      hemorrhage, ventriculomegaly, seizures, bronchopulmonary dysplasia, and
      socioeconomic status) the estimated odds ratio was 1.2 (confidence interval 0.89,
      1.43) per 50 mumol/L increase of total bilirubin. However, in this analysis an
      interaction between bilirubin and intracranial hemorrhage was observed.
      Therefore, the cohort was divided into two groups according to the absence or
      presence of an intracranial hemorrhage. Logistic regression analysis including
      four suspected confounding factors (gestational age, ventriculomegaly, seizures,
      and socioeconomic status) was then again applied. In children who had suffered
      from an intracranial hemorrhage in the neonatal period the estimated odds ratio
      was 1.84 (confidence interval 1.08, 3.15) per 50 mumol/L increase of bilirubin.
      Similar results were obtained treating bilirubin as a categorized exposure. The
      odds ratio in children without a hemorrhage was 1.05 (confidence interval 0.80,
      1.38), probably because of the small number of surviving handicapped children.

PMID- 1371341
TI  - Infant Health and Development Program for low birth weight, premature infants:
      program elements, family participation, and child intelligence.
AB  - The Infant Health and Development Program was an eight-site randomized controlled
      trial testing the efficacy of early intervention to enhance the cognitive,
      behavioral, and health status of low birth weight, premature infants. The 377
      intervention families received for the first 3 years of life: (1) pediatric
      follow-up, (2) home visits, (3) parent support groups, and (4) a systematic
      educational program provided in specialized child development centers. The
      control group (n = 608) received the same pediatric follow-up and referral
      services only. This paper describes the delivery of the intervention and its
      outcomes. A Family Participation Index that was the sum of participation
      frequencies in each of the program modalities unique to the intervention revealed
      that program implementation was not different across the eight sites. Index
      scores did not vary systematically with mother's ethnicity, age, or education or
      with child's birth weight, gender, or neonatal health status; but they were
      positively related to children's IQ scores at age 3. Only 1.9% of children of
      families in the highest tercile of participation scored in the mentally retarded
      range (IQ less than or equal to 70), whereas 3.5% and 13% of children in the
      middle and lowest participation terciles, respectively, scored in the retarded
      range. Similar findings were obtained for borderline intellectual functioning.
      These findings are consistent with previous research linking intensity of
      intervention services with degree of positive cognitive outcomes for high-risk
      infants. The determinants of variations in individual family participation remain
      unknown.

PMID- 1371342
TI  - Identification and management of psychosocial and developmental problems in
      community-based, primary care pediatric practices.
AB  - The importance of psychological and social issues for children's well-being has
      long been recognized and their importance in the practice of pediatrics is well
      documented. However, many of the studies looking at this issue have emphasized
      psychiatric problems rather than issues commonly referred to as the new
      morbidity. The goal of this research was to refocus interest on the problems of
      the new morbidity. This study examined the rates and predictors of psychological
      problems in 19 of 23 randomly chosen pediatric practices in the greater New Haven
      area. Families of all 4- to 8-year-old children were invited to participate and
      to complete the Child Behavior Checklist prior to seeing a clinician. Clinicians
      completed a 13-category checklist of psychosocial and developmental problems
      based on a World Health Organization-sponsored primary care, child-oriented
      classification system. Of the 2006 eligible families, 1886 (94%) participated.
      Clinicians identified at least one psychosocial or developmental problems in 515
      children (27.3%). Thirty-one percent of the children with problems received no
      active intervention, 40% received intervention by the clinician, and 16% were
      referred to specialty services. Not surprisingly, children whose problems were
      rated as moderate or severe were twice as likely to be referred compared with
      children with mild problems. Recognition of a problem was related to four
      characteristics: if the visit was for well child rather than acute care; if the
      clinician felt he or she knew a child well; if the child was male; and if the
      child had unmarried parents (all P less than or equal to .05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1371343
TI  - Methylation of an alpha-foetoprotein gene intragenic site modulates gene
      activity.
AB  - By comparing the methylation pattern of Mspl/Hpall sites in the 5' region of the
      mouse alpha-foetoprotein (AFP) gene of different cells (hepatoma cells, foetal
      and adult liver, fibroblasts), we found a correlation between gene expression and
      unmethylation of a site located in the first intron of the gene. Other sites did
      not show this correlation. In transfection experiments of unmethylated and
      methylated AFP-CAT chimeric constructions, we then showed that methylation of the
      intronic site negatively modulates expression of CAT activity. We also found that
      a DNA segment centered on this site binds nuclear proteins; however methylation
      did not affect protein binding.

PMID- 1371344
TI  - Expression of the P-protein of the human hepatitis B virus in a vaccinia virus
      system and detection of the nucleocapsid-associated P-gene product by
      radiolabelling at newly introduced phosphorylation sites.
AB  - Hepatitis B virus (HBV) contains a particle-associated DNA polymerase/reverse
      transcriptase activity encoded by the P (pol) open reading frame. Due to its low
      abundance, the corresponding protein has so far escaped direct detection and
      structural analysis. As a first step to overcome these difficulties, a series of
      recombinant vaccinia viruses was constructed and used for the synthesis in human
      hepatoma cells of both the authentic full length protein and of its functional
      domains. Pulse chase experiments demonstrated that the P-proteins had very short
      half lives in striking contrast to the viral core protein expressed in parallel
      with the same system. No evidence was obtained for a specific proteolytic
      processing of the P-protein as occurring with retroviral pol gene products.
      Overexpression of P-protein by recombinant vaccinia viruses was then employed to
      develop a highly sensitive detection method based on the in vitro phosphorylation
      of newly introduced target sites for protein kinase A. The usefulness of this
      method was demonstrated in the analysis of encapsidated P-gene products that were
      transiently expressed from an appropriately modified HBV genome. The results
      obtained indicate that the P-protein acts unprocessed, at least during the
      initial steps of nucleocapsid assembly and reverse transcription, and that a
      fraction of the P-protein molecules is linked as such to the viral DNA. Direct
      detection of the hepadnaviral P-protein by in vitro phosphorylation should
      greatly facilitate future analyses on P-protein structure and function.

PMID- 1371345
TI  - The PARP and VSG genes of Trypanosoma brucei do not resemble RNA polymerase II
      transcription units in sensitivity to Sarkosyl in nuclear run-on assays.
AB  - Addition of the ionic detergent N-lauroylsarcosine (Sarkosyl) affects the
      efficiency of transcription of genes of the protozoan Trypanosoma brucei in
      nuclear run-on assays. Transcription of the PARP (procyclin or procyclic acidic
      repetitive protein), variant cell surface glycoprotein (VSG) and ribosomal RNA
      (rRNA) genes was resistant or increased after addition of Sarkosyl. In contrast,
      the transcription of seven protein coding house keeping genes and the mini-exon
      donor RNA (medRNA) genes was completely abolished by the addition of Sarkosyl,
      while the transcription of the 5S rRNA genes showed an intermediate sensitivity.
      We conclude that Sarkosyl can be used to discriminate between the different types
      of trypanosome transcription units. The PARP and VSG protein coding genes had
      previously been postulated to be transcribed by an RNA polymerase I-like enzyme
      on the basis of their resistance to the RNA polymerase II inhibitor alpha
      amanitin. This model is now supported by their resistance to the addition of
      Sarkosyl.

PMID- 1371347
TI  - Nucleotide sequence of a cDNA for an apurinic/apyrimidinic endonuclease from HeLa
      cells.

PMID- 1371346
TI  - Substitutions of a cysteine conserved among DNA cytosine methylases result in a
      variety of phenotypes.
AB  - The proposed mechanism for DNA (cytosine-5)-methyltransferases envisions a key
      role for a cysteine residue. It is expected to form a covalent link with carbon 6
      of the target cytosine, activating the normally inactive carbon 5 for methyl
      transfer. There is a single conserved cysteine among all DNA (cytosine-5)
      methyltransferases making it the candidate nucleophile. We have changed this
      cysteine to other amino acids for the EcoRII methylase; which methylates the
      second cytosine in the sequence 5'-CCWGG-3'. Mutants were tested for their methyl
      transferring ability and for their ability to form covalent complexes with DNA.
      The latter property was tested indirectly with the use of a genetic assay
      involving sensitivity of cells to 5-azacytidine. Replacement of the conserved
      cysteine with glycine, valine, tryptophan or serine led to an apparent loss of
      methyl transferring ability. Interestingly, cells carrying the mutant with serine
      did show sensitivity to 5-azacytidine, suggesting the ability to link to DNA.
      Unexpectedly, substitution of the cysteine with glycine results in the inhibition
      of cell growth and the mutant allele can be maintained in the cells only when it
      is poorly expressed. These results suggest that the conserved cysteine in the
      EcoRII methylase is essential for methylase action and it may play more than one
      role in it.

PMID- 1371348
TI  - The acceptor stem in pre-tRNAs determines the cleavage specificity of RNase P.
AB  - As the result of an unusual RNase P specificity, some special, mature tRNAs have
      acceptor stems with eight instead of the common seven base pairs. The data from
      numerous studies suggest that some features in the tRNA domain of pre-tRNAs are
      important for this behaviour. Here, we show that only five base pairs in the
      acceptor stem of bacterial histidine tRNAs are required to obtain the changed
      cleavage site in an unrelated eukaryotic serine tRNA.

PMID- 1371349
TI  - The kinetics and specificity of cleavage by RNase P is mainly dependent on the
      structure of the amino acid acceptor stem.
AB  - Cleavage by RNase P of the tRNA(His precursor yields a mature tRNA with an 8 base
      pair amino acid acceptor stem instead of the usual 7 base pair stem. Here we
      show, both in vivo and in vitro, that this is mainly dependent on the primary
      structure and length of the acceptor stem in the precursor. Furthermore, the
      tRNA(His) precursor used in this study was processed with a change in both
      kinetic constants, Km and kcat, in comparison to the kinetics of cleavage of the
      precursor to tRNA(Tyr)Su3. Cleavage of a chimeric tRNA precursor showed that
      these altered kinetics were due to a difference in the primary structure and in
      the length of the acceptor stems of these two tRNA precursors. We also studied
      the cleavage reaction as a function of base substitutions at positions -1 and/or
      +73 in the precursor to tRNA(His). Our results suggest that the nucleotide at
      position +73 in tRNA(His) plays a significant role in the kinetics of cleavage of
      its precursor, possibly in product release. In addition, it appears that the C5
      protein of RNase P is involved in the interaction between the enzyme and its
      substrate in a substrate-dependent manner, as previously suggested.

PMID- 1371350
TI  - Analysis of the proximal transcriptional element of the myelin basic protein
      gene.
AB  - The gene encoding myelin basic protein (MBP) contains multiple activator
      sequences spanning upstream of its transcriptional initiation site which
      differentially promote transcription in glial cells. The proximal activator
      sequence, designated MB1, activates transcription in a glial cell type specific
      manner. This sequence resides between -14 to -50 with respect to the RNA
      initiation site of the MBP gene. We have identified within the MB1 sequence a 10
      nucleotide domain, 5'-ACCTTCAAAG-3', that increases transcription of a test
      promoter in glial and Schwann cells. This proximal motif functions in both
      orientations and specifically interacts with a nuclear protein derived from glial
      cells. Results of in vivo competition experiments indicate that this 10
      nucleotide motif positively contributes to the overall transcriptional activity
      obtained from the entire MBP promoter in glial cells.

PMID- 1371351
TI  - Detection of point mutations in human DNA by analysis of RNA conformation
      polymorphism(s).
AB  - RNA molecules were found to separate into numerous metastable conformational
      forms upon non-denaturing gel electrophoresis. The equilibration of the
      conformations was accelerated by heating or mild denaturing conditions. Single
      base substitutions in the sequence of the RNAs caused changes in the
      conformational patterns, including mobility shifts of major and minor
      conformations, appearance of new conformations and loss of other conformations.
      This sequence-dependent RNA conformational polymorphism was used to detect point
      mutations in p53 and, dihydrofolate reductase genes. Sense and anti-sense RNA
      strands corresponding to the same segment of the p53 gene gave entirely different
      conformational patterns. To generate the RNA, short regions of the target genes
      (up to about 250 bp) were amplified by the polymerase chain reaction and the
      resulting DNA segments transcribed to RNA by T7 RNA polymerase. The method is
      rapid, simple, amenable to non-radioactive visualization and was successful in
      several cases when DNA single-strand conformational polymorphism analysis (Orita
      et al. (1989) Genomics 5, 874-879) failed to detect the point mutation.

PMID- 1371352
TI  - Sequence specific generation of a DNA panhandle permits PCR amplification of
      unknown flanking DNA.
AB  - We present a novel method for the PCR amplification of unknown DNA that flanks a
      known segment directly from human genomic DNA. PCR requires that primer annealing
      sites be present on each end of the DNA segment that is to be amplified. In this
      method, known DNA is placed on the uncharacterized side of the sequence of
      interest via DNA polymerase mediated generation of a PCR template that is shaped
      like a pan with a handle. Generation of this template permits specific
      amplification of the unknown sequence. Taq (DNA) polymerase was used to form the
      original template and to generate the PCR product. 2.2 kb of the beta-globin
      gene, and 657 bp of the 5' flanking region of the cystic fibrosis transmembrane
      conductance regulator gene, were amplified directly from human genomic DNA using
      primers that initially flank only one side of the region amplified. This method
      will provide a powerful tool for acquiring DNA sequence information.

PMID- 1371353
TI  - Kinetoplast minicircle DNA of Trypanosoma evansi encode guide RNA genes.

PMID- 1371354
TI  - Neisseria meningitidis encodes an FK506-inhibitable rotamase.
AB  - Eukaryotic peptidyl-prolyl cis-trans isomerases (rotamases) fall into two
      classes, the cyclophilins inhibited by cyclosporin A and the FK506-binding
      proteins inhibited by the macrolide antibiotic FK506. In prokaryotes homologs of
      cyclophilins have been identified and found to have rotamase activity. Sequence
      similarities have been noted between FK506-binding proteins and gene products in
      a number of bacterial species, but whether these bacterial proteins have rotamase
      activity is not known. Using the polymerase chain reaction, we have cloned and
      sequenced a homolog of an FK506-binding protein from Neisseria meningitidis and
      expressed the gene product as a fusion protein with maltose-binding protein. The
      fusion protein was purified by affinity chromatography. By measuring the rate of
      chymotrypsin cleavage of the substrate succinyl-Ala-Ala-Pro-Phe p-nitroanilide,
      we found that the fusion protein had rotamase activity comparable to that of
      human FK506-binding protein. This rotamase activity was inhibited by FK506.

PMID- 1371355
TI  - Identification and synthesis of a major conserved antigenic epitope of
      Trypanosoma cruzi.
AB  - A gene sequence encoding an immunodominant protein with a repetitive epitope from
      the protozoan Trypanosoma cruzi, the causative agent of Chagas disease, was
      cloned and expressed. The identified 10-amino acid repeat is present within a
      high-molecular-weight trypomastigote antigen that appears specific to and
      conserved among T. cruzi isolates. More importantly, greater than 95% of T. cruzi
      infection sera, including both chronic and acute Chagas disease, contained
      elevated levels of antibody to a 15-amino acid synthetic peptide bearing the
      repetitive B-cell epitope. Considering the wide diversity of T. cruzi parasites,
      as well as the broad spectrum of clinical manifestations of Chagas disease, such
      a prevalent immune response among patients is significant and applicable to the
      control of Chagas disease through the diagnosis of T. cruzi infection.

PMID- 1371356
TI  - Calcium-activated potassium channels mediate prejunctional inhibition of
      peripheral sensory nerves.
AB  - Activation of several receptors, including mu-opioid, alpha 2-adrenergic, and
      neuropeptide Y receptors, inhibits excitatory nonadrenergic noncholinergic (NANC)
      neural responses in airways, which were mediated by the release of peptides from
      capsaicin-sensitive sensory nerves. This raises the possibility of a common
      inhibitory mechanism, which may be related to an increase in K+ conductance in
      sensory nerves. To examine this hypothesis, we have studied whether K(+)-channel
      blockers inhibit the effects of neuromodulators of sensory nerves in guinea pig
      bronchi by using selective K(+)-channel blockers. Charybdotoxin (ChTX; 10 nM),
      which blocks large conductance Ca(2+)-activated K(+)-channel function, completely
      blocked and reversed the inhibitory effects of a mu-opioid agonist, neuropeptide
      Y, and an alpha 2-adrenoceptor agonist on excitatory NANC responses. Neither
      inhibitors of ATP-sensitive K+ channels (BRL 31660 or glibenclamide, both at 10
      microM) nor an inhibitor of small conductance Ca(2+)-activated K+ channels
      (apamin; 0.1 microM) were effective. This suggests that ChTX-sensitive K(+)
      channel activation may be a common mechanism for the prejunctional modulation of
      sensory nerves in airways. This may have important implications for the control
      of neurogenic inflammation.

PMID- 1371357
TI  - A potentially critical Hpa II site of the X chromosome-linked PGK1 gene is
      unmethylated prior to the onset of meiosis of human oogenic cells.
AB  - Hpa II site H8 is in the CpG-rich 5' untranslated region of the human X
      chromosome-linked gene for phosphoglycerate kinase 1 (PGK1). It is the only Hpa
      II site in the CpG "island" whose methylation pattern is perfectly correlated
      with transcriptional silence of this gene. We measured DNA methylation at site H8
      in fetal oogonia and oocytes and found, using a quantitative assay based on the
      polymerase chain reaction, that purified germ cells isolated by micromanipulation
      were unmethylated in 47-day to 110-day fetuses, whereas ovaries depleted of germ
      cells and non-ovary tissues were methylated. We conclude that site H8 is
      unmethylated in germ cells prior to the onset of meiosis and reactivation of the
      X chromosome.

PMID- 1371358
TI  - The principal neutralization determinant of simian immunodeficiency virus differs
      from that of human immunodeficiency virus type 1.
AB  - To identify the principal neutralization determinant (PND) of simian
      immunodeficiency virus (SIV), antisera were generated using recombinant gp110
      [the SIV analog of the human immunodeficiency virus type 1 (HIV-1) external
      envelope glycoprotein, gp120], gp140, several large recombinant and proteolytic
      envelope fragments, and synthetic peptides of the SIVmac251 isolate. When
      purified under conditions that retain its native structure, gp110 bound CD4 and
      elicited antisera that neutralized SIVmac251 with high titer. Native gp110 also
      completely inhibited neutralizing antibody in sera from SIVmac251-infected
      macaques. In contrast, denatured gp110 and gp140, large envelope fragments, and
      synthetic peptides (including peptides analogous to the HIV-1 PND) elicited very
      low or undetectable neutralizing antibody titers and did not inhibit neutralizing
      antibody in infected macaque sera. Enzymatically deglycosylated gp110 efficiently
      absorbed neutralizing antibodies from macaque sera, showing that neutralizing
      antibodies primarily bind the protein backbone. A 45-kDa protease digest product,
      mapping to the carboxyl-terminal third of gp110, also completely absorbed
      neutralizing antibodies from infected macaque sera. These results show that the
      PND(s) of this SIV isolate depends on the native conformation and that linear
      peptides corresponding to the V3 loop of SIV envelope, in contrast to that of HIV
      1, do not elicit neutralizing antibody. This may affect the usefulness of SIVmac
      for evaluating HIV-1 envelope vaccine approaches that rely on eliciting
      neutralizing antibody.

PMID- 1371359
TI  - Evidence that hematopoietic stem cells express mouse c-kit but do not depend on
      steel factor for their generation.
AB  - The interaction of the mouse c-kit receptor, designated Kit receptor, and steel
      factor promotes the proliferation and differentiation of hematopoietic progenitor
      cells. Monoclonal antibodies against the extracellular portion of the mouse Kit
      receptor were established. Five percent to 10% of total bone marrow cells
      expressed the Kit receptor, and half of them lack the expression of lineage
      markers. The Kit receptor was expressed on 70-80% of Thy-1.1lo Lin-Sca-1+ cells,
      which express Thy-1.1 antigen at a low level and constitute approximately 0.05%
      of adult bone marrow and fetal liver; by previous studies, these cells have been
      shown to be highly enriched for multipotent hematopoietic stem cells (HSCs) and
      are the only hematopoietic cell subset with this activity. Spleen colony
      formation and long-term multilineage reconstitution activities were contained in
      the Kit+ but not in the Kit- subpopulations of Thy-1lo Lin-Sca-1+ cells from
      adult bone marrow, suggesting that the Kit receptor is expressed on HSCs from the
      earliest stage-i.e., pluripotent HSCs. The role of steel factor in the
      development and self-renewal of HSCs was tested with Sl/Sl homozygote fetuses,
      which lack genes to encode functional steel factor. They were shown to have 30
      40% of the number of HSCs on days 13-15 when compared with normal litermates.
      However, the absolute number of HSCs increased during fetal development in the
      Sl/Sl mice. The results suggest that the Kit receptor-steel factor interaction
      may not be essential for the initiation of hematopoiesis and the self-renewal of
      (at least) fetal HSCs.

PMID- 1371360
TI  - Macrophage activation and immunomodulation by myeloperoxidase.
AB  - Myeloperoxidase (MyPo) is an enzyme found in neutrophils and monocytes that plays
      an important role in the microbicidal and cytocidal activities of these cells.
      The present studies show that this enzyme can also affect both capacities and
      functions of macrophages. When resident peritoneal macrophages from C57BL/6 mice
      were exposed to preparations of either human or canine enzyme in vitro, tumor
      necrosis factor (TNF) was released. The amount of TNF produced was dose dependent
      and could be neutralized with polyclonal anti-TNF. Low levels of interferon were
      also produced by these cells. In addition, exposure of murine macrophages in
      vitro to this enzyme resulted in increased ability to destroy 3T12 target cells.
      Intravenous injection of mice with myeloperoxidase induced the production of both
      TNF and interferon, which could be detected in the sera. Possible mechanisms of
      TNF induction include radical production by myeloperoxidase or ligand-receptor
      interaction by the binding of this enzyme to the mannosyl-fucosyl receptor. These
      results, when taken in their entirety, suggest that this enzyme can modulate the
      immune response through effects on macrophage function.

PMID- 1371361
TI  - In vivo degradation of fetal wound hyaluronic acid results in increased
      fibroplasia, collagen deposition, and neovascularization.
AB  - Fetal tissue repair occurs without acute inflammation, prominent fibroplasia, or
      marked neovascularization. The fetal wound extracellular matrix is rich in
      hyaluronic acid (HA), while collagen is deposited in an organized normal dermal
      pattern. In various biologic systems, including regeneration and development, the
      controlled accumulation and subsequent degradation of hyaluronic acid is
      associated with distinct cellular and matrix events. Therefore, it is
      hypothesized that the abundance of hyaluronic acid in fetal wounds may influence
      cellular and/or matrix events such that tissue repair is highly organized and
      adult-like scarring does not occur. To test this hypothesis, the hyaluronic acid
      content of fetal rabbit wounds was reduced by specific degradation with
      Streptomyces hyaluronidase. Control wounds were treated with either enzyme buffer
      (n = 12) or denatured enzyme solution (n = 8) and exhibited a normal fetal
      healing response with scattered peripheral fibroblasts, a matrix of hyaluronic
      acid, and no infiltrating collagen. In marked contrast, the hyaluronidase-treated
      wounds (n = 14) demonstrated increased fibroblast infiltration, collagen
      deposition, and capillary formation. A significant reduction in the hyaluronic
      acid content of the hyaluronidase-treated wounds was confirmed biochemically.
      Since the degradation of hyaluronic acid resulted in an altered healing response,
      this study demonstrates that hyaluronic acid affects the cellular and matrix
      events in fetal healing and may be partially responsible for the unique qualities
      of this regenerative repair process.

PMID- 1371362
TI  - Malignant biliary obstruction: treatment with expandable metallic stents--follow
      up of 50 consecutive patients.
AB  - A consecutive series of 50 patients with malignant biliary obstruction were
      treated by means of palliative drainage with a metallic expandable stent. Stent
      placement was successful in all patients. The patients were followed up
      prospectively at 2-month intervals over a period of 9-22 months. Forty-one
      patients (82%) died; nine (18%) are still living. The overall patency and
      survival rates for the 50 patients were 5.8 months and 7.5 months, respectively.
      The 30-day mortality rate was 8% (n = 4), the minor complication rate was 18% (n
      = 9), and the major complication rate was 8% (n = 4). One patient (2%) had
      intrahepatic arterial bleeding that required embolization, one (2%) had a right
      subphrenic abscess, and two patients (4%) had transient septic events. Stent
      occlusion requiring a second intervention occurred in 24% of patients (n = 12).
      Excellent palliation was achieved in most patients. No stent migration occurred.
      No great clinical advantages in prolonged patency compared with those of other
      published series involving the use of plastic stents were demonstrated. Ease of
      placement and versatility may offset the high cost of the stent.

PMID- 1371363
TI  - [Circadian variability of rhythm disorders].
AB  - Cardiac arrhythmias exhibit also a circadian variability. It is impressingly
      apparent in sustained ventricular tachycardia and sudden cardiac death.
      Adrenergic stimulation during morning hours, a physiologic event for the
      transition from nocturnal to diurnal activity, appears to be an important
      arrhythmogenic factor (25). The results of the BHAT-study show that beta blocking
      agents may substantially reduce the risk for sudden cardiac death during morning
      hours. This notion should thus be considered in treating patients at risk.

PMID- 1371364
TI  - Role of ELAM-1 in adhesion of monocytes to activated human endothelial cells.
AB  - The role of ELAM-1 in the adhesion of monocytes to HUVEC, activated for 4h with
      TNF, was studied using MoAb ENA2 directed against ELAM-1. In a standard adhesion
      assay at 37 degrees C, F(ab')2 fragments of ENA2 did not, or weakly inhibited
      adhesion. When metabolic activity of the monocytes was reduced by (i) fixing the
      monocytes, (ii) performing the adhesion assay at 4 degrees C, and (iii) combining
      the forementioned conditions, the adhesion of the monocytes was strongly blocked
      by ENA2 and less effective or not by MoAb IB4 anti-CD18. The pattern of adhesion
      of monocytes to HUVEC, activated with TNF assessed at 4 degrees C, paralleled
      ELAM-1 expression on the endothelial cells. Maximal inhibitory effect of ENA2 on
      adhesion was shown 5 h after activation of HUVEC, at which ELAM-1 expression was
      also maximal. Adhesion assessed at 37 degrees C remained enhanced for at least 24
      h, whereas the inhibitory effect of ENA2 followed ELAM-1 expression. Specific
      involvement of ELAM-1 was also confirmed using ELAM-1 transfected COS cells.
      These results indicated that monocytes express a counter structure for ELAM-1 and
      that this counter structure is involved in adhesion.

PMID- 1371365
TI  - Mechanism of transduction by retroviruses.
AB  - Retroviruses can capture cellular sequences and express them as oncogenes.
      Capture has been proposed to be a consequence of the inefficiency of
      polyadenylation of the viral genome that allows the packaging of cellular
      sequences flanking the integrated provirus in virions; after transfer into
      virions, these sequences could be incorporated into the viral genome by
      illegitimate recombination during reverse transcription. As a test for this
      hypothesis, a tissue culture system was developed that mimics the transduction
      process and allows the analysis and quantitation of capture events in a single
      step. In this model, transduction of sequences adjacent to a provirus depends on
      the formation of readthrough transcripts and their transmission in virions and
      leads to various recombinant structures whose formation is independent of
      sequence similarity at the crossover site. Thus, all events in the transduction
      process can be attributed to the action of reverse transcriptase on readthrough
      transcripts without involving deletions of cellular DNA.

PMID- 1371366
TI  - Cholinergic and GABAergic mediations of the effects of apomorphine on serotonin
      neurons.
AB  - Apomorphine (APO) has been shown to elevate tryptophan, serotonin (5-HT), and 5
      hydroxyindoleacetic acid (5-HIAA) concentrations in the dorsal raphe (DR) and its
      corresponding projection site, the striatum, but not in the median raphe (MR) and
      its terminal area, the hippocampus. We have previously demonstrated that these
      effects are indirectly mediated through dopamine (DA) autoreceptors in the
      substantia nigra and possibly gamma-aminobutyric acid (GABA) neurons in or near
      the DR. In the present study, we have further found that the effects of APO on 5
      HT neurons are also mediated through both nicotinic and M1 muscarinic cholinergic
      receptors as well as GABAA receptors in the DR. This suggestion is based on the
      findings that both atropine and mecamylamine antagonized the effects of APO,
      while carbachol at a high dose exerted an effect opposite to that of APO.
      Besides, pirenzepine and bicuculline at low doses also antagonized, whereas
      saclofen did not alter the influence of APO on 5-HT in the striatum. Bicuculline
      at a higher dose enhanced tryptophan and 5-HT measures by itself. None of the
      drugs studied had a significant effect on tryptophan, 5-HT, or 5-HIAA in the
      hippocampus. These results together suggest that DA, ACh, and GABA neurons are
      all involved in the actions of APO on 5-HT, while the direct synaptic
      relationships among these neurotransmitters and the precise anatomical locus for
      these interactions to occur are still unknown. It is possible that APO, by
      inhibiting DA neuron firing in the substantia nigra and through the GABA
      disinhibition mechanism, therefore indirectly activates 5-HT neurons in the DR
      and the striatum. While the above neuronal firing model well explains the
      elevation of 5-HIAA, the simultaneous increases of tryptophan and 5-HT,
      especially tryptophan, may be more readily explained by a mechanism of tryptophan
      uptake upon APO administration. Further anatomical, biochemical, and
      electrophysiological studies are ongoing to test this hypothesis and to clarify
      the circuit and the anatomical locus (loci) for these interactions to occur.

PMID- 1371367
TI  - Differential effects of amfonelic acid on the haloperidol- and clozapine-induced
      increase in extracellular DOPAC in the nucleus accumbens and the striatum.
AB  - This study compares the effects of the nonamphetamine stimulant amfonelic acid on
      the increase in extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) induced by
      haloperidol and clozapine in the nucleus accumbens and the striatum of
      anaesthetized rats. DOPAC was simultaneously recorded in both regions using
      differential pulse voltammetry with electrically pretreated carbon fibre
      electrodes. Amfonelic acid (2.5 mg/kg s.c.) did not alter basal striatal DOPAC
      but produced a significant reduction in extracellular DOPAC in the nucleus
      accumbens. Haloperidol (1 mg/kg s.c.) increased extracellular DOPAC in both
      regions. When amfonelic acid was injected 5 min before haloperidol, the increase
      in DOPAC was potentiated in both the nucleus accumbens and the striatum but with
      a greater effect in the striatum. Clozapine (30 mg/kg i.p.) increased
      extracellular DOPAC in both regions, an effect partially attenuated by amfonelic
      acid in both regions but to a greater extent in the striatum. When ritanserin (5
      mg/kg i.p.), a serotonergic antagonist (5-HT-2), was co-administered with
      haloperidol, the potentiation by amfonelic acid of the increase in extracellular
      DOPAC induced by haloperidol was attenuated in both the nucleus accumbens and the
      striatum. The present results confirm that amfonelic acid can be used to
      discriminate neurochemically between haloperidol and clozapine in vivo. The
      effects of amfonelic acid on the neuroleptic-induced changes in extracellular
      DOPAC were greater in the striatum than the nucleus accumbens. These results
      further demonstrate that both neuroleptics increase dopamine metabolism in the
      two brain regions but by different mechanisms, supporting the view that the
      regulation of dopamine metabolism differs in the two regions.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1371368
TI  - Treatment of scabies and similar infestations.

PMID- 1371369
TI  - Analysis of the antigenic epitopes of hepatitis B surface antigen involved in the
      induction of a protective antibody response.
AB  - Vaccination with hepatitis B surface antigen (HBsAg) has shown that antibody
      directed against the common 'a' determinant of this antigen is protective against
      infection with hepatitis B virus (HBV). In this study the antigenic epitopes of
      the 'a' determinant have been analysed by competitive inhibition assays and by
      binding studies to synthetic peptides using a panel of monoclonal antibodies
      prepared against HBsAg, all of which are shown to recognise the common group
      determinant. One murine monoclonal antibody used in this study, RFHBs1, has been
      shown previously to block infectivity of HBV in susceptible chimpanzees ((1983)
      J. Med. Virol. 16, 89-95). This antibody bound to a cyclical synthetic peptide
      analogue of amino acids 124 to 137 of the major HBsAg polypeptide.

PMID- 1371370
TI  - The immune response to measles virus in mice. T-helper response to the
      nucleoprotein and mapping of the T-helper epitopes.
AB  - The T-helper response to the measles virus nucleoprotein (NP) has been studied in
      mice. The T-cell proliferative response was measured in lymphocytes from mice
      immunized with either a vaccinia measles-NP recombinant virus or a mouse neuro
      adapted measles virus. A T-cell response was obtained with lymphocytes from H2d
      or H2k mice when stimulated with either measles virus or the NP expressed in
      bacteria. The response was CD4+ specific. The T-helper epitopes were mapped using
      truncated NP peptides. The major epitopes in both H2d and H2k mice were
      determined to be between amino acids 67-98. A further T-cell epitope (between
      amino acids 457-525) was identified when H2d mice were immunized with measles
      virus. Studies to quantitate the precursor cells for these epitopes confirmed
      that the region 67-98 of NP was immunodominant in both haplotypes immunized with
      the vaccinia-NP recombinant virus, whereas an additional major epitope was
      observed in the measles virus-infected H2d mice. The primary structure of the
      epitopes determined here are compared to predicted T-cell epitope motifs.

PMID- 1371372
TI  - Relationship between cell-cycle state of erythroid progenitors and fetal
      hemoglobin synthesis.
AB  - DNA-synthesis state of circulating burst forming unit-erythroid (BFU-E) was
      evaluated in patients with sickle cell anemia and correlated with percent of
      fetal hemoglobin synthesized in the BFU-E-derived cells. Percentage of S-phase
      BFU-E inversely correlated with percent fetal hemoglobin synthesized in the BFU-E
      derived cells (simple linear correlation coefficient, r = -0.8, P = 0.0302;
      polynomial regression, R = -0.99, P = 0.0002). This observation is of relevance
      to our understanding of the relationship between the developmental stage of the
      erythroid progenitors and expression of globin genes.

PMID- 1371371
TI  - Characterization and prognostic significance of silent myocardial ischemia on
      predischarge electrocardiographic monitoring in unselected patients with
      myocardial infarction.
AB  - Characteristics and prognostic significance of ischemic ST changes at
      predischarge Holter monitoring were evaluated in 270 consecutive postinfarction
      patients. The 64 patients with ST changes had a greater incidence of non-Q-wave
      myocardial infarction (p less than 0.01) and ventricular premature contractions
      (p less than 0.01); they were more frequently in Moss class greater than 2 (p
      less than 0.01) and they had a lower wall motion score (p less than 0.05). At 2
      year follow-up, patients with ST changes had a higher incidence of cardiac death
      and reinfarction. At multivariate analysis, Killip class (p less than 0.01) and
      ST changes (p less than 0.05) were the most predictive variables; when
      multivariate analysis was repeated including an additional variable--the
      inability to perform a stress test--Killip class was the most significant
      variable (p less than 0.01), and the presence of ST changes showed only
      borderline statistical significance (p less than 0.1). In the subset of patients
      who did not perform the stress test, ST change was the most important variable (p
      less than 0.01), followed by Killip class (p less than 0.05). Thus, after
      myocardial infarction, ST changes during Holter monitoring are associated with a
      poor prognosis and appear useful for stratifying patients who do not perform
      exercise stress tests.

PMID- 1371373
TI  - Striving for a standard of pain relief.

PMID- 1371374
TI  - Implications of "Final Exit".

PMID- 1371375
TI  - Human monoclonal antibody recognizing an antigen associated with ovarian and
      other adenocarcinomas.
AB  - MS2B6, a human monoclonal antibody derived from a patient with advanced ovarian
      cancer, has been used to study the distribution and characteristics of its target
      antigen. The MS2B6 antigen was detected by immunoperoxidase studies in 41 of 41
      epithelial ovarian cancers and in the majority of nonovarian adenocarcinomas.
      Among normal tissues the MS2B6 antigen was found in the adult epithelia of the
      fallopian tube, endometrium, endocervix, colon, bronchus, breast, sweat duct, and
      large renal ducts. No detectable antigen was found in peritoneal epithelia,
      tissue stromal cells, spleen, thymus, or blood-borne cells. Immunoblotting
      analysis showed that the MS2B6 epitope resides on polypeptides of 38, 44, and 60
      kd. The cellular location of the MS2B6 antigen was studied with immunoperoxidase
      and immunofluorescent staining and immunoelectronmicroscopy of ovarian cancer
      ascites tumor cells. The results suggest that in ascites tumor cells the MS2B6
      antigen is located in a layer of the peripheral cytoplasm beginning just below
      the cell membrane. MS2B6 may be useful as an imaging or therapeutic agent.

PMID- 1371376
TI  - Documentation of high-molecular-weight dextran (Hyskon) solution entering the
      serum during hysteroscopy.

PMID- 1371377
TI  - The carotenoid halocynthiaxanthin: a novel inhibitor of the reverse
      transcriptases of human immunodeficiency viruses type 1 and type 2.
AB  - We have studied the effects of a natural carotenoid, identified as
      halocynthiaxanthin, on the enzymatic activities associated with the recombinant
      preparations of the reverse transcriptases (RTs) of human immunodeficiency
      viruses (HIV) types 1 and 2. The carotenoid was found to be a potent inhibitor of
      the RNA-dependent DNA polymerase activity (with 50% inhibition obtained at 5-7
      microM halocynthiaxanthin), whereas the DNA-dependent DNA polymerase function of
      both RTs was significantly less sensitive to the inhibitor. Conversely, the
      ribonuclease H activity associated with the two HIV RTs was essentially
      insensitive to the carotenoid. The RNA-dependent DNA polymerase function of RT is
      the only unique activity found in this enzyme that is not expressed at
      significant levels in uninfected eukaryotic cells. Therefore, it is possible that
      this carotenoid may serve as a good candidate for the development of novel potent
      and specific inhibitors of HIV RT.

PMID- 1371378
TI  - Lymphoproliferative disorder of granular lymphocytes. More questions than
      answers.

PMID- 1371379
TI  - Lymphoproliferative disorder of granular lymphocytes. A heterogeneous disease.
AB  - Lymphoproliferative disorders of granular lymphocytes (LDGLs) represent a family
      of diseases that are morphologically similar but diverse with regard to
      immunophenotype, function, and clonality. In this article, we report three
      informative cases and propose a modification of the current classification of
      LDGLs. Our first case is an example of natural killer cell LDGLs (CD2+, CD3-,
      CD16+, CD57+/-). Based on a review of the literature, we suggest that natural
      killer cell LDGLs can be divided into two subgroups (types 1 and 2) according to
      the expression of CD57. Reduced expression of CD57 may distinguish between
      patients with a poorer prognosis. The remaining two cases illustrate examples of
      T-cell LDGLs (CD2+, CD3+, CD8+, CD57+) that differ mainly in their expression of
      CD16. The CD16+ T-cell LDGLs (type 1) usually show a clonal rearrangement of the
      T-cell receptor-beta chain gene, whereas CD16- T-cell LDGLs (type 2) may show a
      germline configuration, suggesting a reactive rather than a neoplastic process.
      Pathologists should differentiate LDGLs from other chronic lymphoproliferative
      diseases, since most cases evolve slowly and aggressive cytoreductive therapy is
      usually unwarranted.

PMID- 1371380
TI  - Localization of epidermal growth factor receptor by immunohistochemical methods
      in human prostatic carcinoma, prostatic intraepithelial neoplasia, and benign
      hyperplasia.
AB  - The epidermal growth factor receptor (EGFr) is a membrane-bound glycoprotein that
      is present in a wide variety of human normal and malignant tissues. In this study
      EGFr expression in frozen sections of prostate tissue obtained from 40 different
      surgical specimens was examined immunohistochemically with a well-characterized
      monoclonal antibody to EGFr, Ab-1 (Oncogene Science). Twenty cases of prostate
      adenocarcinoma and 20 cases of benign prostatic hyperplasia were studied. Six of
      the 20 cases of adenocarcinoma also contained prostatic intraepithelial neoplasia
      grade III (severe intraductal dysplasia). All of the cases containing benign
      glands showed strong immunostaining in a continuous or nearly continuous pattern,
      with staining restricted to the basal layer of the benign glands. Adenocarcinoma
      lacked immunostaining in 15 (75%) of 20 cases, while the remaining five cases
      (25%) showed diffuse cytoplasmic staining, which was weaker than that seen in the
      benign glands and that lacked basal accentuation. The six cases that contained
      prostatic intraepithelial neoplasia grade III showed a discontinuous basal
      pattern of staining, and the gaps in the staining appeared to correspond to areas
      of disruption of the basal cell layer. We conclude that the antigenic determinant
      recognized by this antibody to EGFr was detected preferentially in the basal
      layer in benign prostatic glands. In contrast, a minority of cases of
      adenocarcinoma expressed EGFr, as assessed by immunoreactivity with the Ab-1
      monoclonal antibody. Prostatic intraepithelial neoplasia grade III expressed EGFr
      with a predominantly discontinuous basal pattern that corresponded to the
      disrupted basal cell layer typical of this process.

PMID- 1371381
TI  - Paneth cell-like metaplasia of the prostate gland.
AB  - We report two cases of Paneth cell-like metaplasia of the prostate gland, one in
      poorly differentiated carcinoma and the second in benign hyperplasia. By light
      microscopy, the Paneth-like cells were indistinguishable from Paneth cells found
      in the normal small intestine and ultrastructurally showed electron-dense
      granules typical of Paneth cells. Immunohistochemical stains were positive for
      prostate-specific antigen and prostatic acid phosphatase and negative for
      lysozyme and alpha 1-antitrypsin. The clinical significance of Paneth cell-like
      metaplasia is unknown and may represent an example of the multipotential
      metaplastic capability of actively dividing cells.

PMID- 1371382
TI  - Malignant phyllodes tumor of the prostate. A case report with immunohistochemical
      and ultrastructural studies.
AB  - Phyllodes tumor of the prostate is a rare neoplasm with cellular or sarcomatoid
      stroma and hyperplastic glands. This lesion shares many histologic features with
      cystosarcoma phyllodes of the breast. Although a malignant variant of phyllodes
      tumor of the prostate has been described, the majority of cases have been
      clinically benign. We report an unusual case of phyllodes tumor of the prostate
      in which the stromal component underwent malignant degeneration, a finding not
      previously described (to our knowledge). Immunohistochemical and ultrastructural
      studies demonstrated smooth-muscle differentiation of the stromal cells.

PMID- 1371383
TI  - Tyrosine phosphorylation is involved in receptor coupling to phospholipase D but
      not phospholipase C in the human neutrophil.
AB  - The tyrosine kinase inhibitors ST271, ST638 and erbstatin inhibited phospholipase
      D (PLD) activity in human neutrophils stimulated by fMet-Leu-Phe, platelet
      activating factor and leukotriene B4. These compounds did not inhibit phorbol
      ester-stimulated PLD, indicating that they do not inhibit PLD per se, but
      probably act at a site between the receptor and the phospholipase. In contrast,
      the protein kinase C inhibitor Ro-31-8220 inhibited phorbol 12,13-dibutyrate- but
      not fMet-Leu-Phe-stimulated PLD activity, arguing against the involvement of
      protein kinase C in the receptor-mediated activation of PLD. ST271 did not
      inhibit Ins(1,4,5)P3 generation, but did inhibit protein tyrosine phosphorylation
      stimulated by fMet-Leu-Phe. The phosphotyrosine phosphatase inhibitor pervanadate
      increased tyrosine phosphorylation and stimulated PLD. These results suggest that
      tyrosine kinase activity is involved in receptor coupling to PLD but not to
      PtdIns(4,5)P2-specific phospholipase C in the human neutrophil.

PMID- 1371385
TI  - Protein synthesis in the newt regenerating limb. Comparative two-dimensional
      PAGE, computer analysis and protein sequencing.
AB  - Protein synthesis has been studied by two-dimensional PAGE during the early limb
      regeneration in the adult newt. Quantitative and statistical analyses have
      provided unique information on overall patterns of protein synthesis as well as
      on specific protein synthesis during formation of the blastema. Furthermore, from
      the patterns in the two-dimensional gels and their quantification, a particular
      protein has been selected and sequenced. Partial sequencing revealed sequence
      similarities to Xenopus type I keratin B2. Expression of this keratin is 10-fold
      greater in the blastema than in the intact limb. The implications of keratin
      expression by the blastema cells are discussed.

PMID- 1371384
TI  - Ca2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide
      synthase.
AB  - L-Arginine-derived nitric oxide (NO) acts as an inter- and intra-cellular signal
      molecule in many mammalian tissues including brain, where it is formed by a
      flavin-containing Ca2+/calmodulin-requiring NO synthase with NADPH,
      tetrahydrobiopterin (H4biopterin) and molecular oxygen as cofactors. We found
      that purified brain NO synthase acted as a Ca2+/calmodulin-dependent NADPH:oxygen
      oxidoreductase, catalysing the formation of hydrogen peroxide at suboptimal
      concentrations of L-arginine or H4biopterin, which inhibited the hydrogen
      peroxide formation with half-maximal effects at 11 microM and 0.3 microM
      respectively. Half-maximal rates of L-citrulline formation were observed at
      closely similar concentrations of these compounds, indicating that the NO
      synthase-catalysed oxygen activation was coupled to the synthesis of L-citrulline
      and NO in the presence of L-arginine and H4biopterin. N omega-Nitro-L-arginine,
      its methyl ester and N omega-monomethyl-L-arginine inhibited the synthesis of L
      citrulline from L-arginine (100 microM) with half-maximal effects at 0.74 microM,
      2.8 microM and 15 microM respectively. The N omega-nitro compounds also blocked
      the substrate-independent generation of hydrogen peroxide, whereas N omega
      monomethyl-L-arginine did not affect this reaction. According to these results,
      activation of brain NO synthase by Ca2+ at subphysiological levels of
      intracellular L-arginine or H4biopterin may result in the formation of reactive
      oxygen species instead of NO, and N omega-nitro-substituted L-arginine analogues
      represent useful tools to effectively block NO synthase-catalysed oxygen
      activation.

PMID- 1371386
TI  - Phorbol 12-myristate 13-acetate activates an electrogenic H(+)-conducting pathway
      in the membrane of neutrophils.
AB  - The mode of activation of an H(+)-conducting pathway present in the membrane of
      neutrophils was investigated. (1) Resting neutrophils released protons through an
      electrogenic Cd(2+)-inhibitable (K0.5 approximately 20 microM) route when a pH
      gradient and appropriate charge compensation was provided. (2) The rate of H+
      efflux was stimulated over 2.5-fold by 4 beta-phorbol 12-myristate 13-acetate
      (PMA; K0.5 approximately 0.7 nM) or by 4 beta-phorbol 12,13-dibutyrate (K0.5
      approximately 20 nM) even when the NADPH oxidase was blocked by p
      chloromercuribenzoate. (3) Staurosporine inhibited the effect of PMA. (4) The H+
      egress was not enhanced by 4 alpha-phorbol 12,13-didecanoate. (5) Low
      concentrations of Cd2+ (less than 40 microM) inhibited the H+ flux without
      influencing the oxidase. The results raise the possibility that protein kinase C
      could be involved in the activation of an electrogenic H(+)-conducting pathway in
      the membrane of neutrophils. The activation of this route by phorbol esters seems
      to be independent of the stimulation of NADPH oxidase.

PMID- 1371387
TI  - Expression of Escherichia coli homoserine kinase in mouse 3T3 cells.
AB  - The Escherichia coli gene for homoserine kinase (thrB) has been cloned into a
      simian-virus-40-based eukaryotic expression vector which also includes a neomycin
      resistance gene. Mouse 3T3 cells transfected with this plasmid were selected for
      resistance and screened for homoserine kinase activity. It has thus been possible
      to isolate clones which are capable of accumulating homoserine O-phosphate when
      supplied with homoserine. In broken-cell preparations the kinetic constants for
      the production of homoserine O-phosphate were similar to those of the wild-type
      E. coli enzyme. These experiments demonstrate that E. coli homoserine kinase can
      be expressed in an animal cell and that it can successfully phosphorylate L
      homoserine in the intact cell utilizing endogenous ATP.

PMID- 1371388
TI  - Mycobacteria and human heat shock protein-specific cytotoxic T lymphocytes in
      rheumatoid synovial inflammation.
AB  - OBJECTIVE: To study the cytotoxic capacity of mycobacteria-specific T lymphocyte
      lines and clones from sites of inflammation in patients with rheumatoid arthritis
      (RA). We also studied antigen specificity, surface phenotype, expression of T
      cell receptors (TCR), and HLA restriction. METHODS: Autologous macrophages (M
      phi) from the synovial membrane (SM), synovial fluid (SF), or peripheral blood
      (PB) were used as target cells in cytotoxicity assays. RESULTS: All SM and SF
      cell lines tested thus far have shown specific lysis of the autologous M phi from
      SM or PB that had been pulsed with BCG (bacillus Calmette-Guerin), but no
      cytotoxicity when the targets were pulsed with irrelevant antigens such as
      tetanus toxoid and Chlamydia. Both CD4+ and CD8+ cells were shown to be involved
      in the specific cytolysis. The majority of the cytotoxic T lymphocyte (CTL) lines
      were TCR alpha/beta + cells. However, both TCR alpha/beta + and TCR gamma/delta +
      clones (TCR delta 1+) from one RA patient showed antigen-specific lysis. Antigen
      specific recognition by a number of CTL lines and clones generated from SF and SM
      was restricted by HLA-DR molecules. Two Mycobacterium bovis 65-kd heat shock
      protein (HSP)-specific TCR alpha/beta + SF T cell clones also lysed M phi that
      had been pulsed with a recombinant human 65-kd HSP. CONCLUSION: Joint
      inflammation and destruction might be partly attributable to a cross-reaction of
      mycobacteria-induced cytotoxic T cells with self HSP.

PMID- 1371389
TI  - Elevated expression of beta 1 and beta 2 integrins, intercellular adhesion
      molecule 1, and endothelial leukocyte adhesion molecule 1 in the skin of patients
      with systemic sclerosis of recent onset.
AB  - OBJECTIVE: To investigate the possible role of integrins and cell adhesion
      molecules in the pathogenesis of the mononuclear cell infiltration and fibrosis
      of skin that occurs in systemic sclerosis (SSc). METHODS: The presence and
      topographic distribution of beta 1, beta 2, and beta 4 integrins, as well as of
      endothelial leukocyte adhesion molecule 1 (ELAM-1) and intercellular adhesion
      molecule 1 (ICAM-1), was examined immunohistochemically in affected skin from 8
      patients with rapidly progressive SSc of recent onset. The expression of the beta
      1 integrin gene was also investigated by in situ hybridization with a human
      sequence-specific complementary DNA. RESULTS: The presence of beta 1 integrin
      epitopes and the corresponding messenger RNA within inflammatory cells
      surrounding small vessels was demonstrated in SSc skin but not in normal skin.
      Lymphocytes positive for beta 2 integrin were also found only in SSc skin, and
      they appeared in close proximity to small blood vessels and collagen bundles.
      Immunostaining for beta 4 integrin epitopes revealed no differences between
      normal and SSc skin. ELAM-1 and ICAM-1 monoclonal antibodies, which identify
      epitopes indicative of endothelial cell activation, stained endothelial cells in
      SSc skin but not normal skin. CONCLUSION: These observations suggest that the
      complex interactions of beta 1 and beta 2 integrins, as well as ELAM-1 and ICAM
      1, may be intimately involved in the pathogenesis of SSc, perhaps by mediating
      the homing and targeting of pathogenetic lymphocytes to the affected tissues.

PMID- 1371390
TI  - Fetal risks with dextrans during delivery.
AB  - Epidural analgesia for caesarean section is increasingly used and is gradually
      replacing general anaesthesia. Hypotension is one of the main risks: preloading
      of the maternal circulation is used to prevent maternal hypotension and its
      consequences. For this, various colloid and crystalloid solutions are used. We
      report a case of maternal anaphylactoid reaction with apparent death in a neonate
      after dextran administration to the mother. After 100ml of a dextran 40 solution
      administered intravenously, immediately before an epidural blockade, the mother
      fainted and developed urticaria and mild respiratory disturbances, without
      hypotension. At that point dextran infusion was stopped. An apparently dead
      neonate was rapidly delivered. Immediate and vigorous cardiopulmonary
      resuscitation was successful. Clonismus appeared 12h later, followed by 3 general
      epileptic fits treated by phenytoin infusion and subsequently oral phenobarbital.
      No aetiology was found. After 2 months of treatment, barbiturates were stopped
      following clinical and electroencephalogram (EEG) improvement. Several similar
      cases of neonatal disorders resulting from preventive dextran administration
      during delivery were studied in a national pharmacovigilance survey in France.
      There were 32 cases reported with moderate maternal anaphylactoid reaction
      associated with severe acute fetal distress; it is probably advisable to take a
      cautious approach and avoid preventive fluid preload by dextran administration.
      Gelatins or crystalloid solutions should be preferred, with intravenous
      vasopressive amine administered promptly and repeated if necessary should
      significant maternal hypotension occur during epidural anaesthesia.

PMID- 1371391
TI  - Regional studies of serotonin and dopamine metabolism and quantification of
      serotonin uptake sites in human cerebral cortex.
AB  - An increasing number of studies have indicated that neuronal metabolism of
      serotonin (5-HT) and other monoamines may be altered in patients with affective
      disorders and in completed suicides. However, studies have yielded discordant
      results. The purpose of this study was to determine the regional variation of 5
      hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), (5-HT) and 5-HT uptake
      sites within the human cerebral cortex. Our sample consisted of 19 patients who
      died suddenly and accidently. Cortical concentrations of 5-HIAA, HVA and 5-HT
      were measured in six regions using an HPLC. 5-HT uptake sites in cortex were
      examined using [3H]-Paroxetine. 5-HT values within each brain were fairly
      constant in cortical regions studied except for the posterior parietal areas. By
      contrast, 5-HIAA values showed a trend towards a rostro-caudal increase, with
      peak values seen at sections corresponding to the post-central gyrus and the
      occipital pole. Using the ratio of 5-HIAA/5-HT as a crude index of 5-HT turnover,
      there was a progressive rostro-caudal increase of values which achieved
      statistical significance: the posterior superior parietal area and the occipital
      pole displayed a greater ratio than the other four cortical regions. HVA values
      were highest in the pre-central region and decreased both rostrally and caudally.
      5-HIAA and HVA values were correlated positively in 5 of 6 cortical areas, while
      5-HIAA and 5-HT were correlated in areas 4 and 5. Results obtaining using [3H]
      Paroxetine suggest that 5-HT uptake sites in the human cortex are distributed
      rather uniformally and are not correlated with 5-HT levels.

PMID- 1371392
TI  - Antibody-targeted photolysis: in vitro immunological, photophysical, and
      cytotoxic properties of monoclonal antibody-dextran-Sn(IV) chlorin e6
      immunoconjugates.
AB  - A set of anti-melanoma immunoconjugates were prepared which contained chlorin e6:
      antibody molar ratios of 18.9:1, 11.2:1, 6.8:1, and 1.7:1. All immunoconjugates
      retained antigen binding activity regardless of the chromophore:antibody
      substitution ratio that was attained. In contrast, the ground-state absorption
      spectra of the immunoconjugates showed features which appeared to be dependent on
      the chromophore:antibody molar ratio. In addition, the quantum yield of singlet
      oxygen generated by the conjugated chromophores was observed to be significantly
      less than that observed with the unbound dye. Time-resolved absorbance
      spectroscopy of the chromophore excited triplet state indicated that the loss of
      singlet oxygen quantum yield resulted from diminished chromophore triplet yield.
      Analysis of data obtained from in vitro photolysis of target melanoma cells, in
      combination with that obtained from the immunochemical and photochemical studies,
      indicates that the observed immunoconjugate phototoxicity can be reasonably
      quantitatively represented by (1) the ability of the immunoconjugate to bind SK
      MEL-2 cell surface antigen, (2) the amount of chromophore localized at the target
      cells by immunoconjugate binding, (3) the delivered dose of light at 634 nm, and
      (4) the singlet oxygen quantum yield of the antibody-bound photosensitizer.
      Though these data argue strongly for photolysis by the cumulative dosage of
      singlet oxygen at the cell membrane, nonetheless, the concurrent photoinduced
      release of other cytotoxic agents should not be ruled out.

PMID- 1371394
TI  - Some chemotherapy agents cause female-specific genetic damage.

PMID- 1371393
TI  - Two types of receptors for human plasminogen on group G streptococci.
AB  - To investigate the nature of plasminogen binding to streptococci, strains
      selected for high reactivity with human plasminogen were examined for binding
      pattern against a panel of plasminogen fragments. The strains included human
      isolates of groups A, C and G as well as bovine isolates of group G. All strains
      reacted substantially with the plasminogen fragment kringle 1-3. Using the
      miniplasminogen fragment (kringle 5 and the B chain) a small but reproducible
      uptake was detected for human group G strains but not for group A or C strains.
      The group G strains of bovine origin on the other hand demonstrated high uptake
      of miniplasminogen, suggesting the possibility of an alternative plasminogen
      receptor for this species. This interpretation was supported by blocking
      experiments with the lysine analogue EACA where low concentrations (1 mM)
      completely blocked plasminogen binding to human streptococci, whereas a 100-fold
      higher concentration was needed for bovine group G strains. Scatchard plots with
      human isolates resulted in straight lines and Kd values were generally in the
      range of 20-80 nM. The number of receptors was estimated to be 45,000 for a
      selected group A strain and about 10,000 for the selected group C and G strains.
      Scatchard analysis with bovine group G isolates on the other hand revealed a two
      phase interaction, supporting the assumption of two different receptor structures
      on these strains. Kd for the first phase was estimated to be about 20 nM (10,000
      20,000 receptors per bacterium), which was similar to the human strains, whereas
      the second phase was in the range of 400-500 nM (50,000 and 150,000 receptors per
      bacterium with two selected strains). Scatchard plots with the miniplasminogen
      fragment as ligand mimicked the phase two reaction with plasminogen, supporting
      the concept that this reaction represents a new and not previously described
      receptor. Both the receptor reacting with the kringle 1-3 portion and the one
      reacting with the miniplasminogen portion bound plasmin and plasminogen with
      similar affinity.

PMID- 1371395
TI  - Effects of capsaicin, bradykinin and prostaglandin E2 in the human skin.
AB  - The actions and interactions of putative mediators of inflammation, such as
      substance P (SP), histamine, bradykinin and prostaglandins (PGE2) were studied in
      human skin. In addition, the effects of capsaicin were examined as it is known to
      release (and to deplete) SP and calcitonin gene-related peptide from C-fibres.
      The flare evoked by bradykinin was abolished by pretreatment with lignocaine
      (local anesthetic), compound 48/80 (mast-cell histamine liberator), mepyramine
      (H1-receptor antagonist) and indomethacin (cyclo-oxygenase inhibitor) but was
      unaffected by atropine and ketanserin (serotonin antagonist). The weal response
      was not reduced by any of the drugs. The flare evoked by capsaicin was abolished
      by lignocaine and indomethacin but was unaffected by compound 48/80, mepyramine,
      atropine and ketanserin. The weal response was reduced by indomethacin. The flare
      response to bradykinin seems to reflect the activation of C-fibres and associated
      mast cells, while the flare response to capsaicin seems to reflect the activation
      of C-fibres only. Repeated injections of capsaicin and bradykinin produced
      tachyphylaxis (and cross-tachyphylaxis) and greatly reduced the SP-evoked flare.
      Capsaicin produced tachyphylaxis also after treatment of the skin with a local
      anaesthetic, suggesting that it develops independently of C-fibre impulse flow.
      The tachyphylaxis produced by bradykinin and capsaicin seems to reflect the
      depletion of messenger peptides from the C-fibres. The flare response to SP
      following capsaicin- or bradykinin-induced desensitization gradually returned to
      normal after 5-8 weeks. The erythema evoked by PGE2 was reduced by 30% following
      pretreatment with lignocaine, mepyramine or compound 48/80.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1371396
TI  - Keratin expression in basal cell carcinomas.
AB  - The keratin phenotype of 15 cases of basal cell carcinoma was assayed
      immunohistochemically using a panel of monospecific antibodies to single keratin
      polypeptides. Whilst tumour tissue strongly expressed primary keratins 5 and 14
      (normally synthesized in basal keratinocytes) no expression of secondary keratins
      1 and 10 (characteristic of skin-type differentiation) was detected. Keratin 17,
      characteristic of the outer hair root sheath, was strongly expressed in all
      tumours. Keratin 19 was also normally expressed in parts of the hair follicle and
      was detected in four cases. The 'high cell turnover' keratin 16 was frequently
      induced in the overlying epidermis, but was rare within tumour tissue. No
      expression of simple epithelial keratins 8 and 18 was detected. Whilst the
      keratin phenotype of tumour cells is similar to that of basal cells within part
      of the hair root sheath, in keeping with suggestions of a follicular origin for
      basal cell carcinomas, the findings are also compatible with an origin from
      interfollicular pluripotent stem cells differentiating towards follicular
      structures.

PMID- 1371397
TI  - Expression of CD11B, CD14 and CD36 antigens by B-cell lymphoma.

PMID- 1371398
TI  - A Nobel Prize for single channel recording.

PMID- 1371399
TI  - Characterization of cDNA encoding mouse DNA repair protein O6-methylguanine-DNA
      methyltransferase and high-level expression of the wild-type and mutant proteins
      in Escherichia coli.
AB  - A mouse cDNA clone encoding O6-methylguanine-DNA methyltransferase (MGMT),
      responsible for repair of mutagenic O6-alkylguanine in DNA, was cloned from a
      lambda gt11 library. On the basis of an open reading frame in cDNA, the mouse
      protein contains 211 amino acids with a molecular mass of 22 kDa. The size and
      the predicted N-terminal sequence of the mouse protein were confirmed
      experimentally. The deduced amino acid sequence of the mouse MGMT is 70%
      homologous to that of the human MGMT. Cysteine-149 was shown to be the only alkyl
      acceptor residue in the mouse protein, in confirmation of the prediction based on
      conserved sequences of different MGMTs. Mouse MGMT protein is recognized by some
      monoclonal antibodies specific for human MGMT. Site-directed mutagenesis was
      utilized to reclone the mouse cDNA in a T7 promoter-based vector for
      overexpression of the native repair protein in Escherichia coli. The mouse
      protein has a tetrapeptide sequence, Pro-Glu-Gly-Val at positions 56-59, absent
      in the human protein. Neither deletion of this tetrapeptide nor substitution of
      valine-169 with alanine affected the activity of the mutant proteins.

PMID- 1371400
TI  - Interaction of acute-phase-inducible and liver-enriched nuclear factors with the
      promoter region of the mouse alpha 1-acid glycoprotein gene-1.
AB  - The synthesis and secretion of several acute-phase proteins increases markedly
      following physiological stress. alpha 1-Acid glycoprotein (AGP), a major acute
      phase reactant made by the liver, is strongly induced by inflammatory agents such
      as lipopolysaccharide (LPS). Nuclear run-on assay showed a 17-fold increase in
      the rate of AGP transcription 4 h following LPS injection. DNase I footprinting
      assays revealed multiple protein binding domains in the mouse AGP-1 promoter
      region. Region B (-104 to -91) is protected by a liver-enriched transcription
      factor that is heat labile and in limiting quantity. An adjacent region, C (-125
      to -104), is well-protected by nuclear extracts from hepatocytes. Electrophoretic
      mobility shift assays indicated that only one DNA-protein complex can form with
      an oligonucleotide corresponding to region B. However, nuclear proteins from
      untreated mouse liver can form three strong complexes (C1, C2, and C3) and a weak
      one (C4) with oligonucleotide C. An acute-phase-inducible DNA-binding protein (AP
      DBP) forms complex 4. A dramatic increase (over 11-fold) in AP-DBP binding
      activity is seen with nuclear proteins from LPS-stimulated animals.
      Interestingly, AP-DBP, a heat-stable factor, can form heterodimers with the
      transcription factor CCAAT/enhancer binding protein (C/EBP). Furthermore,
      purified C/EBP also binds avidly to region C. Our studies indicate that several
      liver-enriched nuclear factors can interact with AGP-1 promoter and that AP-DBP
      binds to the AGP-1 promoter with high affinity only during the acute-phase
      induction.

PMID- 1371401
TI  - Lipophilic cations: a group of model substrates for the multidrug-resistance
      transporter.
AB  - The possibility that simple lipophilic cations such as tetraphenylphosphonium
      (TPA+), triphenylmethylphosphonium (TPMP+), and diphenyldimethylphosphonium
      (DDP+) are substrates for the multidrug-resistance transport protein, P
      glycoprotein, was tested. Hamster cells transfected with and overexpressing mouse
      mdr1 or mouse mdr3 exhibit high levels of resistance to TPP+ and TPA+ (20-fold)
      and somewhat lower levels of resistance to TPMP+ and DDP+ (3-12-fold).
      Transfected cell clones expressing mdr1 or mdr3 mutants with decreased activity
      against drugs of the MDR spectrum (e.g., Vinca alkaloids and anthracyclines) also
      show reduced resistance to lipophilic cations. Studies with radiolabeled TPP+ and
      TPA+ demonstrate that increased resistance to cytotoxic concentrations of these
      lipophilic cations is correlated quantitatively with a decrease in intracellular
      accumulation in mdr1- and mdr3-transfected cells. This decreased intracellular
      accumulation is shown to be strictly dependent on intact intracellular nucleotide
      triphosphate pools and is reversed by verapamil, a known competitive inhibitor of
      P-glycoprotein. Taken together, these results demonstrate that lipophilic cations
      are a new class of substrates for P-glycoprotein and can be used to study its
      mechanism of action in homologous and heterologous systems.

PMID- 1371402
TI  - The early genetic response to light in the green unicellular alga Chlamydomonas
      eugametos grown under light/dark cycles involves genes that represent direct
      responses to light and photosynthesis.
AB  - In the green unicellular alga Chlamydomonas eugametos, cellular division is
      readily synchronized by light/dark cycles. Under these conditions, light
      initiates photosynthetic growth in daughter cells and begins the G1 phase. Genes
      whose expression is regulated upon illumination are likely to be important
      mechanisms controlling cell proliferation. To identify some of those genes, two
      cDNA libraries were prepared with poly(A)+ extracted from cells either stimulated
      with light for 1 h or held in darkness (quiescent cells) during the same period.
      To restrict our analysis to those genes that are part of the primary response,
      cells were incubated in presence of cycloheximide. Differential screening of
      approximately 40,000 clones in each library revealed 44 clones which hybridize
      preferentially with a [32P] cDNA probe derived from RNA of light-stimulated cells
      and 15 clones which react selectively with a [32P] cDNA probe synthesized from
      poly(A)+ RNA of quiescent cells. Cross-hybridization of these clones identified 4
      independent sequences in the light-induced (LI) collection and 2 in the uninduced
      (LR) library. Four of these cDNAs correspond to mRNAs that are positively or
      negatively regulated upon activation of photosynthesis. One clone represents a
      mRNA that accumulates transitorily at both transitions. Finally, LI818 cDNA
      identifies a new chlorophyll a/b-binding (cab) gene family whose mRNA
      accumulation is controlled by light and a circadian oscillator. The endogenous
      timing system controls LI818 mRNA accumulation so that it precedes the onset of
      illumination by a few hours. On the other hand, light affects LI818 mRNA levels
      independently of active photosynthesis.

PMID- 1371403
TI  - Characterization of a stress-induced, developmentally regulated gene family from
      soybean.
AB  - We describe a family of stress-induced, developmentally regulated soybean genes
      for which cDNAs have been obtained from two different cultivars (Glycine max cv.
      Mandarin and Glycine max cv. Williams). The mRNAs corresponding to these cDNAs,
      called SAM22 and H4, respectively, accumulate predominantly in the roots of
      soybean seedlings but are present at high levels in the roots and leaves of
      mature plants. SAM22 accumulation is especially dramatic in senescent leaves. In
      addition, SAM22 accumulation can be induced on young leaves by wounding or by
      transpiration-mediated uptake of salicylic acid, methyl viologen, fungal
      elicitor, hydrogen peroxide or sodium phosphate (pH 6.9). Taken together, these
      data indicate that the genes corresponding to SAM22 and H4 are induced by various
      stresses and developmental cues. Southern blot analysis indicates that multiple
      copies of sequences related to SAM22 exist in the soybean genome. We also show
      that the nucleotide sequences of the cDNAs corresponding to SAM22 and H4 are 86%
      identical at the nucleotide level to each other and 70% identical at the amino
      acid level to the 'disease resistance response proteins' of Pisum sativum.

PMID- 1371405
TI  - The lectin gene family of Ricinus communis: cloning of a functional ricin gene
      and three lectin pseudogenes.
AB  - Molecular hybridisation using a ricin cDNA probe has revealed that the
      ricin/Ricinus communis agglutinin (RCA) multigene family is composed of
      approximately eight members. Several genomic clones containing preproricin and
      preproricin-like sequences have been isolated. Partial analysis of three
      different genomic clones by DNA sequencing and ribonuclease protection has
      indicated that at least three members of the lectin gene family are non
      functional. None of the original seventeen positive clones isolated appears to
      contain a Ricinus communis agglutinin (RCA) gene. One gene member analysed
      (pCBG3H1) represents a functional ricin gene similar in coding sequence to the
      published cDNA sequence and possesses typical eukaryotic consensus sequences and
      seed-specific elements within the flanking sequences. Investigation at the
      transcriptional level of the expression pattern of this gene revealed that mRNA
      accumulates during the post-testa stages of seed development. The pattern of
      accumulation of steady-state transcripts correlates closely with that previously
      observed at the protein and translatable RNA levels.

PMID- 1371404
TI  - Accumulation of wound-inducible ACC synthase transcript in tomato fruit is
      inhibited by salicylic acid and polyamines.
AB  - Regulation of wound-inducible 1-aminocyclopropane-1-carboxylic acid (ACC)
      synthase expression was studied in tomato fruit (Lycopersicon esculentum cv. Pik
      Red). A 70 base oligonucleotide probe homologous to published ACC synthase cDNA
      sequences was successfully used to identify and analyze regulation of a wound
      inducible transcript. The 1.8 kb ACC synthase transcript increased upon wounding
      the fruit as well as during fruit ripening. Salicylic acid, an inhibitor of wound
      responsive genes in tomato, inhibited the wound-induced accumulation of the ACC
      synthase transcript. Further, polyamines (putrescine, spermidine and spermine)
      that have anti-senescence properties and have been shown to inhibit the
      development of ACC synthase activity, inhibited the accumulation of the wound
      inducible ACC synthase transcript. The inhibition by spermine was greater than
      that caused by putrescine or spermidine. The transcript level of a wound
      repressible glycine-rich protein gene and that of the constitutively expressed
      rRNA were not affected as markedly by either salicylic acid or polyamines. These
      data suggest that salicylic acid and polyamines may specifically regulate
      ethylene biosynthesis at the level of ACC synthase transcript accumulation.

PMID- 1371406
TI  - Characterization of cDNAs encoding CuZn-superoxide dismutases in Scots pine.
AB  - A Scots pine (Pinus sylvestris L.) cDNA library was screened with two
      heterologous cDNA probes (P31 and T10) encoding cytosolic and chloroplastic
      superoxide dismutases (SOD) from tomato. Several positive clones for cytosolic
      and chloroplastic superoxide dismutases were isolated, subcloned, mapped and
      sequenced. One of the cDNA clones (PS3) had a full-length open reading frame of
      465 bp corresponding to 154 amino acid residues and showed approximately 85%
      homology with the amino acid sequences of angiosperm cytosolic SOD counterparts.
      Another cDNA clone (PST13) was incomplete, but encoded a putative protein with
      93% homology to pea and tomato chloroplastic superoxide dismutase. The derived
      amino acid sequence from both cDNA clones matched the corresponding N-terminal
      amino acid sequence of the purified mature SOD isozymes. Northern blot
      hybridizations showed that, cytosolic and chloroplastic CuZn-SOD are expressed at
      different levels in Scots pine organs. Sequence data and Southern blot
      hybridization confirm that CuZn-SODs in Scots pine belong to a multigene family.
      The results are discussed in relation to earlier observations of CuZn-SODs in
      plants.

PMID- 1371408
TI  - Molecular identification of a soybean protein kinase gene family by using PCR.
AB  - In this study we report identification of six members of a protein kinase gene
      family from soybean (Glycine max L.). Two fully degenerate oligonucleotide
      primers corresponding to two conserved motifs (DLK-PENV and GTHEYLAPE) in the
      catalytic domains of eukaryotic protein serine/threonine kinases were used in a
      polymerase chain reaction (PCR) to amplify soybean cDNA. Sequence analysis showed
      that 28 of the PCR sequences represented six different putative protein
      serine/threonine kinases. These results not only demonstrate that catalytic
      domains of protein kinases are highly conserved between plants and other
      eukaryotes but also suggest that there are multiple genes encoding protein
      kinases in plants.

PMID- 1371407
TI  - Cloning of a cDNA for rape chloroplast 3-isopropylmalate dehydrogenase by genetic
      complementation in yeast.
AB  - Both insect and mammalian genes have previously been cloned by genetic
      complementation in yeast. In the present report, we show that the method can be
      applied also to plants. Thus, we have cloned a rape cDNA for 3-isopropylmalate
      dehydrogenase (IMDH) by complementation of a yeast leu2 mutation. The cDNA
      encodes a 52 kDA protein which has a putative chloroplast transit peptide. The in
      vitro made protein is imported into chloroplasts, concomitantly with a
      proteolytic cleavage. We conclude that the rape cDNA encodes a chloroplast IMDH.
      However, Southern analysis revealed that the corresponding gene is nuclear. In a
      comparison of IMDH sequences from various species, we found that the rape IMDH is
      more similar to bacterial than to eukaryotic proteins. This suggests that the
      rape gene could be of chloroplast origin, but has moved to the nucleus during
      evolution.

PMID- 1371409
TI  - Isolation and nucleotide sequence of a cDNA clone encoding the beta subunit of
      mitochondrial ATP synthase from Hevea brasiliensis.

PMID- 1371410
TI  - Treatment of hairy cell leukemia.

PMID- 1371412
TI  - Expression of receptors for granulocyte colony-stimulating factor on neutrophils
      from patients with severe congenital neutropenia and cyclic neutropenia.
AB  - We studied granulocyte colony-stimulating factor (G-CSF) binding sites on
      neutrophils from patients with severe congenital neutropenia (SCN; Kostmann
      syndrome) and cyclic neutropenia (CN) during treatment with recombinant human
      (rh) G-CSF. G-CSF receptor expression was measured by scatchard analysis.
      Neutrophils from six healthy controls expressed between 480 and 1,210 binding
      sites per cell, whereas neutrophils from five SCN patients expressed increased
      numbers of G-CSF binding sites ranging between 2,100 and 3,900 per cell.
      Neutrophils from four patients with CN expressed 350 to 1,600 binding sites per
      cell. The affinity of rhG-CSF to its receptor was similar in patients and
      controls. These data suggest that SCN patients and CN patients are not defective
      in G-CSF receptor expression as judged by the numbers of G-CSF binding sites and
      binding affinity; however, we cannot exclude defects in parts of the G-CSF
      receptor that may be involved in the signal transduction pathway.

PMID- 1371411
TI  - Liposomal encapsulation of azidothymidine results in decreased hematopoietic
      toxicity and enhanced activity against murine acquired immunodeficiency syndrome.
AB  - This study has determined the effect of liposomal encapsulation on the
      hematopoietic toxicity and antiviral activity of 3'-azido-3'-deoxythymidine (AZT)
      in mice. Daily intravenous administration in the dose range 0.4 to 10 mg/kg body
      weight for 5 days significantly depressed bone marrow cellularity with a
      corresponding decrease in red blood cell, blood neutrophil, and monocyte numbers.
      Maximum toxicity was seen at 2 mg/kg or greater. Liposomal encapsulation of AZT
      and administration at 2 mg/kg abrogated the toxicity of AZT. The neutrophil
      inflammatory response to thioglycollate injected intraperitoneally was
      significantly inhibited by AZT at all doses, whereas liposomal AZT was without
      effect. The inhibitory activity of AZT against Concanavalin A (Con A)-stimulated
      splenic lymphocyte proliferation in vitro was reduced on liposomal encapsulation
      of AZT, while treatment of mice with liposomal AZT but not free AZT resulted in a
      significant reduction of Con A-stimulated proliferation. Liposomal AZT was more
      effective than AZT in preventing the development of plasma reverse transcriptase
      activity and the depletion of Thy 1.2(+)-L3T4+ T cells after infection of mice
      with LP-BM5 retrovirus. These results indicate that AZT-induced hematopoietic
      toxicity may not be a limiting factor for antiviral therapy, and that the use of
      liposomes to deliver AZT results in enhanced antiretroviral activity in mice.

PMID- 1371413
TI  - Molecular cloning of cDNAs for the human granulocyte colony-stimulating factor
      receptor from HL-60 and mapping of the gene to chromosome region 1p32-34.
AB  - Early studies examining the effects of purified or recombinant granulocyte colony
      stimulating factor (G-CSF) on human leukemia cell lines demonstrated that some
      cell lines, such as HL-60, could be induced to differentiate in response to G
      CSF. In two recent studies reporting the cloning of the human G-CSF receptor
      (hGCSFR), four classes of receptor cDNA were identified and, surprisingly, the
      message for this receptor was reportedly expressed by HL-60 at either very low
      levels or not at all. Using a mouse G-CSF receptor probe, we cloned and sequenced
      a cDNA for hGCSFR from an HL-60 cDNA library in plasmid and used it to identify
      31 additional clones from an HL-60 cDNA library in phage. Polymerase chain
      reaction analysis of the 31 phage clones established that 29 were derived from
      class I hGCSFR mRNA, one was derived from class III mRNA, and one was derived
      from class IV mRNA. In addition, the hGCSFR gene was chromosomally localized by
      Southern blot analysis of its segregation pattern in a panel of rodent-human
      hybrid DNAs using the radiolabeled cDNA probe. The hGCSFR locus was present in
      hybrids retaining the distal short arm of human chromosome 1 and absent in
      hybrids that did not retain this region. Chromosomal in situ hybridization
      refined the localization of the hGCSFR gene to region 1p32-p34. The combination
      of hybrid DNA analysis and in situ hybridization places the hGCSFR gene telomeric
      to the CSF1, JUN, and TCL-5 loci.

PMID- 1371414
TI  - Differential roles of stromal cells, interleukin-7, and kit-ligand in the
      regulation of B lymphopoiesis.
AB  - Newly formed B lymphocytes are a population of rapidly renewed cells in the bone
      marrow of mammals and their steady state production presumably depends on a
      cascade of regulatory cells and cytokines. Although considerable information has
      been forthcoming about the role of interleukin-7 (IL-7) in potentiating pre-B
      cell proliferation, few studies have addressed the possibility that multiple
      cytokines are involved in the progression of early events in cellular
      differentiation and proliferation in this hematopoietic lineage. Our laboratory
      previously described pre-B-cell differentiation mediated by the bone marrow
      stromal cell line S17. In this study, we further delineate the role of stromal
      cells in differentiation and proliferation of pre-B cells. These experiments show
      that the stromal cell line S17 potentiates the proliferative effect of IL-7 on B
      lineage cells and that this S17-derived potentiator can be replaced with
      recombinant kit-ligand (KL). Our results further show that pre-B-cell formation
      from B220-, Ig- progenitor cells and expression of mu heavy chain of
      immunoglobulin is uniquely dependent on the presence of S17 stromal cells and
      cannot be reproduced with IL-7, KL, or costimulation with both IL-7 and KL. These
      data contribute to a rapidly evolving model of stromal cell regulation of B-cell
      production in the marrow and suggest unique roles for IL-7, KL, and as yet
      uncharacterized stromal cell-derived lymphokines in this process.

PMID- 1371415
TI  - Mobilization of peripheral blood progenitor cells by sequential administration of
      interleukin-3 and granulocyte-macrophage colony-stimulating factor following
      polychemotherapy with etoposide, ifosfamide, and cisplatin.
AB  - We report on the requirements that have to be met to combine a standard-dose
      chemotherapy regimen with broad antitumor activity with the mobilization of
      peripheral blood hematopoietic progenitor cells. Thirty-two cancer patients were
      given a 1-day course of chemotherapy consisting of etoposide (VP16), ifosfamide,
      and cisplatin (VIP; n = 46 cycles), followed by the combined sequential
      administration of recombinant human interleukin-3 (rhIL-3) and recombinant human
      granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Control patients
      received GM-CSF alone or were treated without cytokines. Maximum numbers of
      peripheral blood progenitor cells (PBPC) were recruited on day 13 to 17 after
      chemotherapy, with a median of 418 CD34+ cells/microL blood (range, 106 to 1,841)
      in IL-3/GM-CSF-treated patients, 426 CD34+/microL (range, 191 to 1,380) in GM-CSF
      treated patients, and 46 CD34+/microL (range, 15 to 148) in patients treated
      without cytokines. In parallel, there was an increase in myeloid (10,490 colony
      forming unit-granulocyte-macrophage [CFU-GM]/mL blood; range, 1,000 to 23,400),
      as well as erythroid (10,660 burst-forming unit-erythroid [BFU-E]/mL blood;
      range, 3,870 to 24,300) and multipotential (840 CFU-granulocyte, erythrocyte,
      monocyte, megakaryocyte [GEMM]/mL blood; range, 160 to 2,070) progenitor cells in
      IL-3 plus GM-CSF-treated patients. In GM-CSF-treated patients, significantly less
      precursor cells of all lineages were mobilized, particularly multipotential
      progenitors (400 CFU-GEMM/mL blood; range, 200 to 2,150). Only small numbers of
      CD34+ cells and clonogenic progenitor cells could be recruited in intensively
      pretreated patients. Our data document that after standard-dose chemotherapy
      induced bone marrow hypoplasia, IL-3 plus GM-CSF can be used to recruit PBPC,
      which might shorten the hematopoietic recovery after high-dose chemotherapy in
      chemosensitive lymphomas or solid tumors.

PMID- 1371416
TI  - Cardiopulmonary bypass induces leukocyte-platelet adhesion.
AB  - Cardiopulmonary bypass (CPB) has been demonstrated to activate platelets,
      producing an increased number of circulating platelets that have undergone alpha
      granule release and express granule membrane protein-140 (GMP-140) on their
      surface. In vitro, GMP-140 mediates activated platelet adhesion to neutrophils
      (PMN) and monocytes, causing the formation of leukocyte-platelet conjugates.
      Using a newly developed assay that measures the percentage of circulating
      leukocyte-platelet conjugates in whole blood, we studied 17 patients undergoing
      CPB and have determined that (1) monocyte-platelet conjugates increased
      significantly during CPB, from 18% +/- 1.5% to 44% +/- 4.5% (mean +/- SEM) by the
      end of CPB, while PMN-platelet conjugates increased only slightly and lymphocyte
      platelet conjugates decreased; (2) the time course of the increase in monocyte-
      and PMN-platelet conjugates paralleled that of the increase in circulating
      activated platelets, as determined by the presence of surface GMP-140; and (3)
      monocyte activation, as assessed by increased surface expression of CD11b, showed
      a gradual increase similar to the increase in monocyte-platelet conjugates, while
      PMN surface CD11b peaked immediately after the start of CPB. We conclude that
      CPB, through increased platelet GMP-140 expression, causes formation of monocyte
      platelet, and to a lesser extent, PMN-platelet conjugates. The activation of
      monocytes and PMN on CPB, as evidenced by CD11b expression, occurs with differing
      time courses.

PMID- 1371417
TI  - Liver-specific RNA processing of the ubiquitously transcribed rat fibrinogen
      gamma-chain gene.
AB  - Fibrinogen gamma-chains differ in amino acid sequence at the carboxyterminus due
      to alternative 3' RNA processing. Previous studies reported differences between
      humans and rats in the mechanism of gamma-chain RNA processing and that it was a
      nonregulated event. To test the hypothesis that rat gamma-chain RNA processing
      involves both alternative splicing and poly(A) site selection and that it is
      regulated in a tissue-specific manner, we determined the tissue distribution of
      gamma-chain mRNA expression and the pattern of gamma-chain pre-mRNA processing.
      The results of in situ hybridization demonstrated that gamma A and gamma B
      transcripts were localized to and codistributed in liver hepatocytes, indicating
      that no subset of cells process gamma B mRNA. The ubiquitous expression of the
      fibrinogen gamma-chain promoter was demonstrated in marrow, lung, brain, and
      liver by RNase protection using a 5'-specific gamma-chain probe. RNase protection
      studies to map 3' RNA processing sites suggested that, in addition to the distal
      poly(A) signal previously identified, two alternative poly(A) signals within the
      last intron (ATTAAA and AATAAA) were used only in liver to produce gamma B
      transcripts. Approximately equal usage of the three poly(A) signals (27%, 37%,
      and 36%, respectively) to form the 3' end of mature gamma B transcripts suggested
      that poly(A) site selection is random. These results indicate that splicing of
      the last intron to produce gamma A mRNA is the ubiquitous and constitutive
      pattern of gamma-chain RNA processing, while retention of the last intron to
      produce gamma B mRNAs is the tissue-specific and regulated pattern of gamma-chain
      RNA processing. The pattern of rat gamma-chain RNA processing is similar to
      human, implying that the mechanism is conserved. These data support a mechanism
      of tissue-specific splice site selection predominating over poly(A) site
      selection in gamma-chain pre-mRNA processing. The expression of both fibrinogen
      gamma-chain transcripts in liver, rather than mutually exclusive expression in
      liver and other tissues, provides a new model for studying tissue-specific
      alternative 3' end formation regulatory mechanisms.

PMID- 1371418
TI  - Heme oxygenase is a positive acute-phase reactant in human Hep3B hepatoma cells.
AB  - The effects of human interleukin-6 (hIL-6), the major acute-phase inducer, on the
      level of the transcript of microsomal heme oxygenase (HO) were examined in a
      human hepatoma cell line, Hep3B. Messenger RNAs (mRNAs) encoding HO and
      haptoglobin (Hpt) increased after hIL-6 treatment in a time- and dose-dependent
      manner. hIL-6 had no effect on the induction of heat-shock protein 70 (hsp70)
      mRNA, suggesting that the induction of HO by hIL-6 is regulated by a different
      mechanism from that which mediates the heat-shock induction of this enzyme. The
      hIL-6-mediated induction of HO mRNA was completely abrogated by simultaneous
      treatment of cells with actinomycin D, but not with cycloheximide, suggesting
      that the induction occurs at the level of transcription. A nuclear factor was
      shown both in untreated, and in the hIL-6-treated Hep3B cells that binds
      specifically to the IL-6-responsive element (IL6-RE) of the human HO gene. These
      findings suggest that HO is a positive acute-phase reactant in this human liver
      derived cell line, and that the nuclear factor specific to the IL6-RE may be
      involved in the activation of the HO gene after hIL-6 treatment.

PMID- 1371419
TI  - Defective c-myc and c-myb RNA turnover in acute myeloid leukemia cells.
AB  - Dysregulated expression of the c-myc and c-myb protooncogenes has been implicated
      in the pathogenesis of acute myeloid leukemia (AML). To elucidate mechanisms of c
      myc dysregulation in AML cells, we studied c-myc RNA turnover in peripheral blood
      blasts from eight patients using actinomycin D transcription blockade. Rapid c
      myc RNA turnover was seen in cells from six patients, with half-lives of
      approximately 30 minutes, similar to those reported in normal myeloid cells, in
      HL-60 cells, and in other cell lines. c-myc RNA turnover was prolonged in cells
      of the other two patients, with half-lives of greater than 75 minutes. c-fos RNA
      turnover was rapid in blasts from all eight patients, with half-lives of
      approximately 15 minutes. Stabilization of GM-CSF transcripts was not observed.
      In contrast, c-myb RNA half-lives were greater than 75 minutes in cells of the
      two patients with prolonged c-myc RNA turnover, as compared to 30 minutes in
      cells of the other six patients. Enhanced stability of both c-myc and c-myb RNA
      species suggests that a defect exists in a trans-acting factor that destabilizes
      both of these normally labile RNAs. Incomplete correlation between c-myc RNA
      levels and half-lives indicates regulation of c-myc expression at the level of
      transcription or nuclear transport in addition to posttranscriptional regulation.

PMID- 1371420
TI  - Detection of Philadelphia chromosome-positive acute lymphoblastic leukemia by
      polymerase chain reaction: possible eradication of minimal residual disease by
      marrow transplantation.
AB  - Minimal residual disease (MRD) in patients with Philadelphia chromosome-positive
      acute lymphoblastic leukemia (Ph1 ALL) who received allogeneic (n = 9) or
      autologous (n = 6) bone marrow transplantation (BMT) was evaluated by the
      polymerase chain reaction (PCR) for the bcr-abl transcript. Twelve patients
      received BMT at the time of hematologic and cytogenetic remission. However, MRD
      was detected in 8 of 10 patients evaluated. Seven patients, including three who
      had MRD before BMT, continue to have a disease-free survival 5 to 64 months after
      BMT. Twenty-one specimens obtained from these patients at various times after BMT
      did not show MRD. In three patients, MRD detected just before BMT seems to be
      eradicated by BMT protocol. The other eight patients developed cytogenetic or
      hematologic relapses 2 to 8 months after BMT. Seven of 14 samples from these
      patients demonstrated MRD, which preceded clinical relapse by 3 to 9 weeks. Thus,
      this technique for the detection of MRD appears to be useful for the more precise
      assessment of various antileukemia therapies and for early detection of leukemia
      recurrence.

PMID- 1371422
TI  - Dehydrochlorination of delta-isomer of hexachlorocyclohexane by a soil bacterium,
      Pseudomonas sp.

PMID- 1371421
TI  - Immune responses to Aeromonas hydrophila in cat fish (Heteropneustis fossilis)
      exposed to cadmium and hexachlorocyclohexane.

PMID- 1371423
TI  - Biological monitoring of chlorinated pesticides among exposed workers of mango
      orchards: a case study in tropical climate.

PMID- 1371424
TI  - Studies of mineralization in tissue culture: optimal conditions for cartilage
      calcification.
AB  - The optimal conditions for obtaining a calcified cartilage matrix approximating
      that which exists in situ were established in a differentiating chick limb bud
      mesenchymal cell culture system. Using cells from stage 21-24 embryos in a micro
      mass culture, at an optimal density of 0.5 million cells/20 microliters spot, the
      deposition of small crystals of hydroxyapatite on a collagenous matrix and matrix
      vesicles was detected by day 21 using X-ray diffraction, FT-IR microscopy, and
      electron microscopy. Optimal media, containing 1.1 mM Ca, 4 mM P, 25
      micrograms/ml vitamin C, 0.3 mg/ml glutamine, no Hepes buffer, and 10% fetal
      bovine serum, produced matrix resembling the calcifying cartilage matrix of fetal
      chick long bones. Interestingly, higher concentrations of fetal bovine serum had
      an inhibitory effect on calcification. The cartilage phenotype was confirmed
      based on the cellular expression of cartilage collagen and proteoglycan mRNAs,
      the presence of type II and type X collagen, and cartilage type proteoglycan at
      the light microscopic level, and the presence of chondrocytes and matrix vesicles
      at the EM level. The system is proposed as a model for evaluating the events in
      cell mediated cartilage calcification.

PMID- 1371425
TI  - Prostate-specific antigen and other prognostic factors in patients with hormone
      resistant prostatic cancer undergoing experimental treatment.
AB  - In 58 patients with progressive hormone-resistant metastatic cancer of the
      prostate, prostate-specific antigen (PSA) greater than 100 micrograms/l,
      haemoglobin less than 12.0 g/dl and pronounced fatigue were found to be
      independent adverse prognostic factors. These risk factors distinguished a
      subgroup of patients with a median survival of 9 months (none or only 1 risk
      factor present) from a subgroup with a median survival of 4 months (greater than
      or equal to 2 risk factors present). The clinician should be reluctant to enter
      patients from the second group into complicated and resource-demanding clinical
      studies, particularly if such trials require frequent and inconvenient follow-up
      examinations.

PMID- 1371426
TI  - Potential for targeting head and neck squamous cell carcinoma with monoclonal
      antibody K984.
AB  - In previous reports we have described the development of mAb K984, reactive with
      an epitope expressed on the outer cell surface of undifferentiated, proliferating
      cells in normal stratified squamous epithelia and their neoplastic counterparts.
      The K984 antigen was also found to be homogeneously expressed by in vitro
      cultured squamous cell carcinoma (SCC) cell lines. In the present study we
      demonstrate that mAb K984 induces a significant, dose-dependent growth inhibition
      when SCC cells are grown in vitro as monolayer cultures in the presence of mAb
      K984. These data seem to indicate that mAb K984 has potential for tumour
      targeting, especially in a therapeutic setting. As a first approach to evaluate
      the suitability of mAb K984 for tumour targeting in vivo, radiolabelled mAb K984
      was administered to SCC-xenografted nude mice. Selective tumour accumulation of
      mAb K984 was observed. Tumour to blood ratios and tumour to non-tumour ratios, as
      based on the biodistribution data, were at least ten times higher in case of the
      specific mAb K984 when compared to another non-specific, isotype-matched control
      antibody. mAb K984 was also capable of visualizing tumour deposits in xenografted
      nude mice. The corollary of these findings is that the mAb K984-defined antigen
      probably is involved in the regulation of proliferation of stratified squamous
      epithelium and squamous cell carcinoma and that mAb K984 has potential for
      specific tumour targeting.

PMID- 1371427
TI  - Phorbol 12-myristate 13-acetate induces resistance of human melanoma cells to
      natural-killer- and lymphokine-activated-killer-mediated cytotoxicity.
AB  - Human melanoma cells are sensitive to the lytic activity of natural killer (NK)
      and lymphokine-activated killer (LAK) cells in vitro. The events resulting in
      tumour cell killing by lymphocytic effectors have not been completely clarified,
      and the same target cell determinants regulating responsiveness to immune
      cytolysis have not yet been identified. Indeed, changes in the differentiative
      status of leukemia cells as well as in the expression of major histocompatibility
      complex (MHC) antigens have been described to modulate sensitivity to cytotoxic
      effectors; moreover surface expression of adhesion factors or extracellular
      matrix proteins by the cancer cells can promote the activation of the cytolytic
      effectors and has been described to correlate with tumour cell sensitivity to
      cytolytic cells. We reasoned that treatment with differentiation inducers could
      modulate melanoma cell sensitivity to NK and LAK cells. The present study
      demonstrates that human melanoma GLL-19 cells, when treated with the phorbol
      diester phorbol 12-myristate 13-acetate (PMA) in vitro, undergo growth inhibition
      and neuron-like differentiation. Moreover, PMA treatment induces an evident
      inhibition of GLL-19 cell sensitivity to NK- and LAK-mediated cytotoxicity. GLL
      19 cells express constitutively MHC class I antigens. PMA treatment, however,
      does not modify the expression of MHC class I and class II DR antigens in human
      melanoma GLL-19 cells. We have finally evaluated the effects of PMA on the
      expression at the cell surface of adhesion factors such as ICAM-1, and
      extracellular matrix proteins such as collagen IV, laminin and fibronectin; we
      have also studied the expression of the integrin vitronectin receptor, a membrane
      receptor for adhesive proteins. While adhesion factors and extracellular matrix
      proteins appear to play an important role in the interaction between immune
      effector and tumour target, it can be supposed that the modulation of such
      membrane-associated proteins or glycoproteins induces NK and LAK resistance in
      cancer cells. We indeed found that PMA treatment induced in GLL-19 a marked
      reduction of membrane expression of collagen IV and ICAM-1; moreover PMA reduced
      the cell membrane expression of the integrin vitronectin receptor. On the other
      hand, membrane expression of fibronectin and laminin was not affected by PMA.
      These data indicate that the acquisition of a NK- and LAK-resistant phenotype by
      GLL-19 cells occurs together with cell differentiation, down-regulation of
      membrane expression of collagen IV, ICAM-1 and vitronectin receptor, but in the
      absence of changes in MHC antigens.

PMID- 1371428
TI  - Direct measurement of L-type Ca2+ window current in heart cells.
AB  - The activation and inactivation relations of several ion channel currents
      overlap, suggesting the existence of a steady-state or "window" current. We
      studied L-type Ca2+ channel window current in single cardiac Purkinje cells using
      a voltage-clamp protocol by which channels were first inactivated nearly
      completely during a long-duration depolarizing step, and then the recovery of
      Ca2+ current was observed during repolarizing steps into the L-type Ca2+ window
      voltage range. With these conditions, a small-amplitude inward Ca2+ current
      gradually developed after repolarization to voltages within the window but not
      after steps to voltages positive or negative to it. Window current was suppressed
      by Cd2+ (50 microM), nifedipine (1 microM), and nicardipine (1 microM), and it
      was augmented by isoproterenol (5 microM) and Bay K 8644 (1 microM). At voltages
      at which window current developed, L-type Ca2+ channels also recovered to a
      closed state from which they could be reopened by an additional depolarizing
      step. At voltages positive to the window range, channel recovery to a closed
      state(s) was absent, whereas at voltages negative to the window range, channel
      recovery to a closed state(s) increased, as expected from the "steady-state"
      inactivation relation. Our results provide direct measurement of L-type Ca2+
      window current and distinguish it from other processes, such as slow
      inactivation. Our findings support the postulate that within a window there occur
      channel transitions from inactivated to closed states, and these channels
      (re)open, and this process may occur repetitively. Some physiological and
      pathophysiological roles for L-type Ca2+ window current are discussed.

PMID- 1371429
TI  - Ionic currents in single cells from human cystic artery.
AB  - The patch-clamp technique was used to study the electrophysiological properties
      of single smooth muscle cells obtained from the human cystic artery. These cells
      contracted on exposure to high K+ and had a mean resting potential of -36 +/- 7
      mV. Under current clamp, regenerative responses could not be elicited when
      depolarizing pulses were applied. Voltage-clamp measurements demonstrated that a
      large fraction of the outward current was inhibited by tetraethylammonium (5-10
      mM) or Ca2+ channel blockers and that it was enhanced by increasing [Ca2+]o,
      suggesting that it is a Ca(2+)-activated K+ current. In addition, spontaneous
      transient outward currents that were sensitive to extracellular Ca2+ were
      observed in some cells. In cell-attached patch-clamp recordings, Ca(2+)-activated
      K+ channels that had a conductance of 117 pS were consistently identified. At
      negative potentials (approximately -60 mV), these single-channel events
      deactivated completely and very quickly, suggesting that they do not control the
      resting membrane potential in healthy cystic artery cells. Ca2+ currents that
      were recorded using Ba2+ (10 mM) as the charge carrier were enhanced by the
      dihydropyridine agonist, Bay K 8644, and blocked by nifedipine (0.1 microM). Only
      one type of Ca2+ current, the L-type, could be identified in these cells. These
      results demonstrate that the major ionic currents in the human cystic artery are
      similar to other mammalian arteries and indicate that this tissue will be a
      useful model for studying the metabolic and pharmacological modulation of ionic
      currents in human vascular smooth muscle.

PMID- 1371430
TI  - Active oxygen species stimulate vascular smooth muscle cell growth and proto
      oncogene expression.
AB  - Vascular smooth muscle cells (VSMCs) proliferate in response to arterial injury.
      Recent findings suggest that, in addition to platelet-derived growth factors,
      growth factors from inflammatory cells and endothelial cells at the site of
      injury may contribute to VSMC proliferation. We hypothesized that a common
      mechanism by which endothelial cells and inflammatory cells stimulate VSMC growth
      could be the active oxygen species (i.e., O2-, H2O2, and .OH) generated during
      arterial injury. Using xanthine/xanthine oxidase to generate active oxygen
      species, we studied the effects of these agents on VSMC growth. Xanthine/xanthine
      oxidase (100 microM xanthine and 5 microunits/ml xanthine oxidase) stimulated DNA
      synthesis in growth-arrested VSMCs by 180% over untreated cells. Administration
      of the scavenging enzymes superoxide dismutase and catalase demonstrated that
      H2O2 was primarily responsible for xanthine/xanthine oxidase-induced VSMC DNA
      synthesis. H2O2 directly increased VSMC DNA synthesis and cell number (maximal at
      200 microM) but decreased DNA synthesis of endothelial cells and fibroblasts.
      This effect was protein kinase C independent: sphingosine, a potent protein
      kinase C inhibitor, failed to block H2O2-induced VSMC DNA synthesis. H2O2 (200
      microM) stimulated c-myc and c-fos mRNA levels by fourfold and 20-fold,
      respectively, as compared with quiescent levels. In contrast to DNA synthesis,
      H2O2 induction of c-myc and c-fos mRNA was primarily protein kinase C dependent.
      These findings show that H2O2 specifically increases VSMC DNA synthesis and
      suggest a role for this oxidant in intimal proliferation, especially after
      arterial injury.

PMID- 1371431
TI  - Abnormal electrical properties of myocytes from chronically infarcted canine
      heart. Alterations in Vmax and the transient outward current.
AB  - BACKGROUND: Reentrant ventricular arrhythmias can occur in the surviving muscle
      fibers of the epicardial border zone of the canine heart 5 days after coronary
      artery occlusion. To understand the cellular basis of these arrhythmias, we
      developed a method of dispersing myocytes (IZs) from the epicardial border zone.
      METHODS AND RESULTS: We compared the electrophysiological properties of IZs with
      those of cells dispersed from the epicardium of control noninfarcted (NZs) and of
      sham-operated animals (NZsham). Transmembrane action potentials of IZs are
      reduced in total action potential amplitude and maximum upstroke velocity
      compared with NZs. However, resting potential of IZs is no different from that of
      NZs. Action potential duration at -10 mV is significantly reduced in IZs compared
      with control, and IZ potentials do not show the typical "spike and dome"
      morphology that is evident in all NZs. Using Vmax as an indirect measure of the
      peak inward current available for the upstroke of the action potential, we found
      that the availability curve for IZs is significantly different from the NZ curve.
      Furthermore, the time course of recovery of Vmax after a depolarizing voltage
      clamp step was significantly altered in IZs. Using whole-cell voltage clamp
      techniques, we determined that the voltage-dependent, Ca(2+)-independent, 4
      aminopyridine-sensitive transient outward current (ito1) occurred in all NZs (n =
      16) but existed in only 37% of IZs (n = 16). There was a significant reduction in
      the density of ito1 elicited by depolarizing steps in those IZs showing ito1
      compared with ito1 density in NZs. CONCLUSIONS: We have developed a single-cell
      model of cells that survive in the infarcted heart. Our studies indicate that
      there are changes in Vmax in IZs. In addition, there is no prominent phase 1 of
      repolarization in IZ action potentials. This is consistent with the dramatic loss
      in the function of the ionic channel responsible for the voltage-dependent
      transient outward current, ito1.

PMID- 1371432
TI  - Recent insights into coronary collateral circulation.
AB  - The functional significance of coronary collaterals in humans has been debated
      for many years. Correlations have now been made between the anatomic appearance
      of coronary collateral vessels visualized at the time of intracoronary
      thrombolytic therapy during the acute phase of myocardial infarction and the
      creatine kinase time--activity curve, infarct size, and aneurysm formation. These
      studies demonstrate a protective role of collaterals in hearts with coronary
      obstructive disease, showing smaller infarcts, less aneurysm formation, and
      improved ventricular function compared with patients in whom collaterals were not
      visualized. There is ample evidence that collaterals respond to myocardial
      ischemia by opening preexistent channels. When the cardiac myocyte is rendered
      ischemic, collaterals develop actively by growth with DNA replication and mitosis
      of endothelial and smooth muscle cells. Heparin-binding growth factors are
      present in the heart, but their biological activity is quiescent under normal
      physiological conditions. Once ischemia develops, these factors are activated and
      become available for receptor occupation, which may initiate angiogenesis after
      exposure to exogenous heparin. This characteristic of heparin to potentiate the
      mitogenic activity of acidic fibroblast growth factor has recently been used in
      the clinical setting as a possible therapeutic modality in patients with coronary
      artery disease. Patients performing 20 rounds of exercise serially after
      receiving intravenous injection of heparin showed significantly greater increases
      in exercise capacity and improvement of clinical symptoms compared with the
      control group who performed the same exercise without heparin. Further study of
      neovascularization may lead to a new therapeutic strategy for ischemic heart
      disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371434
TI  - Restoration of nigrostriatal synaptic circuitry, striatal mRNA expression, and
      motor symmetry following embryonic substantia nigra grafts.

PMID- 1371433
TI  - Is there a role for the tumor cell integrin alpha IIb beta 3 and cytoskeleton in
      tumor cell-platelet interaction?
AB  - In vitro tumor cell-platelet interaction was examined using B16 amelanotic (B16a)
      melanoma cells. These tumor cells express the alpha IIb beta 3-type cytoadhesin.
      Aggregation studies demonstrated that tumor cell surface alpha IIb beta 3
      mediates the recognition of platelets since pretreatment of tumor cells with
      antibody against alpha IIb beta 3 prevents platelet-tumor cell interaction as
      well as platelet activation measured by aggregometry, platelet eicosanoid
      metabolism and ultrastructural analysis. In B16a cells, disruption of the
      microfilaments and intermediate filaments inhibits mobility of alpha IIb beta 3
      on the cell surface. Microtubules do not play a role in receptor mobility,
      because B16a cells do not possess well-defined microtubules in interphase and
      colchicine does not affect receptor mobility. Disruption of microfilaments or
      intermediate filaments results in an inhibition of tumor cell-platelet
      interaction as evidenced by aggregometry studies and ultrastructural analysis. We
      suggest that platelet interaction with tumor cells begins with alpha IIb beta 3
      mediated receptor recognition followed by not only platelet activation but also
      microfilament- and vimentin intermediate filament-dependent tumor cell
      activation.

PMID- 1371436
TI  - The electrocorticogram in relation to physiology and behavior: a new analysis.
AB  - Recent research in animals indicates that the generalized regulation of cortical
      activity that is represented by activation of the electrocorticogram is dependent
      on ascending cholinergic and serotonergic projections. The effect of the activity
      of these systems is correlated with concurrent motor activity in a detailed and
      specific manner. Combined blockade of central cholinergic and serotonergic
      function results in impaired cerebral control of behavior, i.e., a dementia-like
      syndrome. Previous concepts, which held that electrocortical activation is
      mediated via a reticulo-thalamo-cortical pathway and that it is related primarily
      to arousal, vigilance, and the sleep-waking cycle appear to be incomplete or
      erroneous.

PMID- 1371435
TI  - Effect of H2-receptor antagonists on rat liver cytosolic acetyl CoA:arylamine N
      acetyltransferase activity.
AB  - This investigation examined the effect of cimetidine, famotidine, and ranitidine
      on rat liver acetyl CoA:arylamine N-acetyltransferase (NAT) activity. Studies
      were conducted using procainamide and p-aminobenzoic acid as substrate probes for
      NAT isozymes II and I, respectively. At an inhibitor:substrate ratio of 2:1,
      ranitidine, cimetidine, and famotidine reduced NAT II activity by 9, 48, and 75%,
      respectively. At this same ratio, none of the H2-receptor antagonists
      significantly reduced NAT I activity. The inhibition of NAT II activity by
      cimetidine and famotidine was mixed in nature, with characteristics consistent
      with predominantly competitive inhibitors. Preincubation of NAT with acetyl CoA
      did not attenuate the inhibitory effects of famotidine, suggesting this agent
      does not associate with the sulfhydryl of the critical cysteine residue on NAT.
      These results indicate the ability of H2-receptor antagonists to inhibit NAT
      activity with some degree of specificity for the two isozymes and significant
      differences in inhibitory potency between the antagonists.

PMID- 1371437
TI  - Interaction of afferent impulses in the human primary sensorimotor cortex.
AB  - We recorded somatosensory evoked magnetic fields (SEFs) over the hand area of the
      primary sensorimotor cortex (SMI) in 6 healthy adults in 2 sets of experiments to
      study interaction of afferent impulses. In experiment 1, SEFs were elicited by
      contralateral median nerve (MC) stimuli presented alone and 40 msec after a
      conditioning stimulus to the contralateral ulnar (UC), ipsilateral median (MI) or
      contralateral tibial (TC) nerve. N20m, P30m and P60m deflections to MC
      stimulation were markedly attenuated by preceding UC stimulation whereas N40m was
      enhanced, and a novel P80m emerged. In contrast, MI or TC stimulation did not
      affect the responses to MC. In experiment 2, the time course of recovery of N20m
      to median nerve stimuli was studied after stimulation of the adjacent ulnar and
      of the same median nerve. The recovery curves were similar for both conditioning
      stimuli with nearly full recovery of N20m at 120 msec. The results indicate
      marked interaction of impulses from ipsilateral median and ulnar nerves in human
      SMI, but no evidence was found of interaction from the two hands or from
      ipsilateral hand and foot.

PMID- 1371438
TI  - Generator sites of spontaneous MEG activity during sleep.
AB  - We have recorded spontaneous magnetoencephalographic (MEG) activity during
      overnight natural sleep in 4 healthy adults with a 24-channel SQUID gradiometer,
      mainly over the sides of the head. All sleep stages were obtained. The MEG wave
      forms resembled the EEG phenomena recorded simultaneously from the scalp midline,
      but the electric and magnetic signals did not always coincide. The source
      locations of different signals were studied by using a current dipole model. The
      equivalent sources of magnetic transients, resembling and often coinciding with
      the electric vertex waves and K-complexes, as well as the transients during REM
      sleep, were concentrated within a volume of 4 x 4 x 3 cm3 in the inferior
      parietal lobe. For spindles and slow waves, no such focal generators were found.

PMID- 1371439
TI  - Sequential changes in electroencephalogram continuity in very premature infants.
AB  - This study was conducted to quantify sequential changes in electroencephalogram
      (EEG) continuity for 24 h in very premature infants. For a total of 122 days,
      continuous 2-channel EEG recording was conducted for 28 premature infants from 26
      to 33 weeks of conceptional age (CA). None of the infants showed evidence of
      neurological impairment during hospitalization. Normal neurological outcome was
      noted at a minimum 12 months of age. By classifying each 5.5 min epoch according
      to EEG continuity, the number of contiguous epochs of each series of
      discontinuous type (DTs) and the number of epochs between two series of
      discontinuous type (IDTIs) were counted at each CA. The duration of DT decreased
      with increasing CA. The mean duration remained at 13-16 min after 29 weeks CA.
      The mean duration of each IDTI increased with CA, up to about 1 h at 33 weeks. A
      constant period of DTs was noted at longer intervals with increasing CA. These
      changes appear related to the development of sleep state organization with CA.

PMID- 1371440
TI  - Abnormality of background EEG determined by the entropy of power spectra in
      epileptic patients.
AB  - Relationships between epileptiform discharges and background activity were
      examined by power spectral entropy (PSE), measuring a degree of EEG irregularity.
      The EEGs were recorded from 10 electrodes placed at F3, F4, C3, C4, T3, T4, P3,
      P4, O1 and O2 in 11 epileptic patients with widespread lateralized spike and wave
      complexes (SWCs). Bipolar records were also made from the antero-posterior
      derivations. The locations of the maximum PSE coincided with those of the maximum
      amplitude of SWC in most of the patients. Bipolar derivations with the maximum
      PSE always included the locations with the maximum PSE obtained from a linked
      ears reference. Pearson's correlation coefficient between PSE and SWC amplitude
      was 0.62 +/- 0.14 (mean +/- S.D.) in 11 patients, thus indicating that the scalp
      distribution of PSE was closely related to that of the amplitude of SWC. These
      findings suggest that the background EEG is disorganized in or near the
      epileptogenic focus. A focal background abnormality can therefore be estimated by
      PSE.

PMID- 1371441
TI  - Quantitative EEG changes due to cerebral vasoconstriction. Indomethacin versus
      hyperventilation-induced reduction in cerebral blood flow in normal subjects.
AB  - Hyperventilation leads to an increase in slow EEG activity as well as to a
      decrease in alpha activity. These effects may be considered a result of reduction
      in cerebral blood flow due to vasoconstriction, but metabolic factors, such as
      alkalosis and the increased formation of cerebral lactate, may also have to be
      taken into account. As indomethacin decreases cerebral blood flow it is possible
      to study cerebral vasoconstriction, without concomitant metabolic alkalosis or
      cerebral lactate formation. Two parallel groups of 12 healthy male subjects (age
      20-25) were studied with quantitative EEG (qEEG) and cerebral blood flow velocity
      as parameters. In the first group the effect of 100 mg indomethacin was studied.
      In the parallel group a standardized hyperventilation procedure was performed. In
      the indomethacin group the blood flow velocity decreased to 60% of the initial
      value; the qEEG showed a 0.5 Hz slowing of the alpha peak frequency (P less than
      0.01) and a decrease in the power of the alpha band without any change in the
      delta or theta band. In the hyperventilation group the blood flow velocity
      decreased to 63% of the initial value and the qEEG showed a marked increase in
      delta and theta activity (P less than 0.01), but a non-significant change in
      alpha peak frequency. Indomethacin and hyperventilation caused similar degrees of
      vasoconstriction; however, the increase in qEEG slow wave activity, which was
      observed only in the hyperventilation group, is apparently related to metabolic
      rather than haemodynamic factors.

PMID- 1371442
TI  - Pupillary light reflex latency in patients with multiple sclerosis.
AB  - In 46 patients with definite multiple sclerosis (MS) the direct and indirect
      pupillary light reflex latency (PLRL) and visual evoked potential (VEP) latency
      of the P100 were measured for each eye separately. The PLRL was measured at both
      photopic and scotopic illuminance level, using an infrared light reflection
      technique (IRIS). On average the PLRL increased at the scotopic illuminance level
      as compared with the photopic (P less than 0.0001). An abnormal VEP was found in
      80.4% of the patients, while 26.1% and 29.7% had an abnormal direct PLRL at
      photopic and scotopic illuminance level respectively. No correlations were found
      between PLRL and VEP or visual acuity. In MS patients with unilateral optic signs
      (optic neuritis or slowly progressive visual failure) a relative prolonged PLRL
      could be demonstrated in the symptomatic eye as compared to the asymptomatic eye.
      Based on formulae to quantitate relative afferent and efferent impairments of the
      pupillary pathway, it is demonstrated that prolonged PLRL measurements mainly
      reflect the nerve conduction in the efferent pupillary pathway.

PMID- 1371443
TI  - The laplacian analysis of the pattern onset response in man.
AB  - The pattern onset VEP described by means of principal component analysis was
      shown to be composed of at least two overlapping time components, of which one
      has a striate and the other an extrastriate origin. This analysis was based on a
      multi (24)-electrode registration. We looked for a technique that can
      distinguish, with a limited number of electrodes, between the striate and
      extrastriate components and can be applied in the clinic. The calculation of a 5
      point 'Laplacian' operator over the striate area enhances the contribution of the
      striate source relative to the contribution of the extrastriate source that lies
      outside the area of the operator, and vice versa. We applied two 5-point
      operators, one centered on Oz and the other 6 cm left of Oz. This montage allowed
      for the selective recording of the striate and extrastriate activities
      separately. This was proved by means of an adaptation paradigm that selectively
      reduced the striate contribution. Application of the laplacian operator for
      clinical practice is exemplified by means of the VEPs of a patient suspected of
      psychogenic hemianopsia.

PMID- 1371444
TI  - Estimates of visually evoked cortical currents.
AB  - We have measured magnetic fields evoked by the onset of checkerboard-like
      sectorial patterns presented at 16 locations near the center of the visual field.
      Small stimuli (less than 2 degrees), which, nevertheless, gave sufficiently
      strong responses to enable source localization, were used to limit cortical
      activation to a small area, thus simplifying the analysis of the magnetic field
      data. We focused on optimizing the experimental design: cortical sources could be
      located from measurements at just one position of our 24-channel magnetometer and
      with as few as 15-20 repetitions of the stimulus. Minimum-norm-estimate maps
      calculated from even a single response showed reproducible features of the
      current distribution, which was, 80-100 msec after the pattern onset,
      retinotopically organized in the occipital lobe. Since magnetoencephalography can
      reveal cortical locations with a precision of 2-3 mm, our procedure appears
      promising for further studies of cortical retinotopy and visual field defects.

PMID- 1371445
TI  - Italian Society of Clinical Neurophysiology, annual meeting. Verona, 1-2 June
      1990. Abstracts.

PMID- 1371446
TI  - Characterization of binding sites for oxyntomodulin on a somatostatin-secreting
      cell line (RIN T3).
AB  - Oxyntomodulin (OXM), a glucagon-containing peptide extended at its C-terminal end
      by an octapeptide, is a potent inhibitor of gastric acid secretion in rat and
      man. OXM appears to act on gastric mucosa at least partially through a
      stimulation of gastric somatostatin release. We have investigated the effects of
      OXM on a somatostatin-secreting cell line (RIN T3) derived from a radiation
      induced rat insulinoma and characterized specific binding sites for this peptide.
      OXM increased somatostatin release with an ED50 of 2.3 nM. OXM also stimulated
      the cAMP accumulation in intact RIN T3 cells and adenylate cyclase activity in
      RIN T3 cell membranes with ED50 values of 0.5 and 11 nM, respectively. On these
      parameters, glucagon was 10-30 times less potent than OXM. Forskolin,
      isobutylmethylxanthine, and 8-bromo-cAMP mimicked the effect of OXM on
      somatostatin release. Specific binding for mono-[125I]OXM was dependent upon time
      and membrane concentration. Binding of mono-[125I]OXM was inhibited by OXM and
      glucagon in a concentration-dependent manner, with dissociation constants (Kd) of
      4.5 and 43 nM, respectively. The nonhydrolyzable analogs of GTP (guanosine 5',3-O
      (thio)triphosphate and guanosine 5' (beta,gamma-imino)triphosphate decreased the
      binding of mono-[125I]OXM to its binding sites. Covalent cross-linking of mono
      [125I]OXM or mono-[125I]glucagon to RIN T3 cell membranes followed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated a single
      radiolabeled band at 63,000 mol wt, which differed from that observed after cross
      linking with liver plasma membranes (55,000 mol wt). These results demonstrate
      the presence of specific high affinity binding sites for OXM in a somatostatin
      secreting cell line (RIN T3) and their coupling to adenylate cyclase via guanine
      nucleotide-binding proteins.

PMID- 1371447
TI  - Elevated beta-cell calmodulin produces a unique insulin secretory defect in
      transgenic mice.
AB  - Transgenic mice with elevated levels of beta-cell calmodulin develop severe
      diabetes even though pancreatic beta-cells contain reserve levels of insulin.
      Electron microscopic examination of transgenic pancreas confirmed the presence of
      abundant insulin secretory granules and failed to reveal obvious morphological
      abnormalities. These observations suggested that excess calmodulin may
      specifically impair the secretory process. To directly assess the effect of
      excess calmodulin on beta-cell function we have isolated pancreatic islets from
      transgenic animals. Transgenic islets from 6- to 8-day-old mice used 40% less
      glucose than normal islets and contained 58% of the normal insulin content, 90%
      of the normal glucagon content, and 5-fold higher levels of calmodulin than
      islets from control mice of the same age. Parallel perifusions of normal and
      transgenic islets confirmed that excess calmodulin inhibited glucose-stimulated
      insulin secretion; first phase secretion was reduced by 60%, and second phase
      secretion was essentially absent. Static assays were performed to assess the
      response to other secretagogues. All fuel secretagogues tested were ineffective
      in stimulating insulin secretion from transgenic islets. Secretion in response to
      depolarizing levels of potassium was also severely impaired. The
      phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine increased transgenic
      secretion, but not to the level obtained in normal islets. Of the compounds
      examined, only phorbol 12-myristate 13-acetate and carbachol, two substances
      thought to act in beta-cells by stimulation of protein kinase-C, produced
      equivalent secretion in normal and transgenic islets. Phorbol 12-myristate 13
      acetate also appeared to restore second phase secretion in transgenic islets.
      These results indicate that the initial period of calmodulin-induced diabetes is
      due to a secretory defect. This defect appears to be distal to membrane
      depolarization and is selective for the second phase of insulin secretion.

PMID- 1371448
TI  - Involvement of the plasmin system in dissociation of the insulin-like growth
      factor-binding protein complex.
AB  - A variety of treatments, including acid, heparin, and proteases, are known to
      free insulin-like growth factors (IGFs) from their binding proteins (IGFBPs).
      However, the physiologically relevant mechanism regulating the interaction of
      IGFs and IGFBPs is unknown. We report here the ability of plasmin to dissociate
      IGFs from IGFBPs. In chromatographic experiments, plasmin completely dissociated
      complexes of [125I] IGF-I-BP and [125I]IGF-II-BP formed with purified decidual
      IGFBP (hIGFBP-1) or IGFBPs present in medium conditioned by human osteosarcoma MG
      63 cells. Plasmin dissociation of IGF-BP complexes was dose dependent. Neither
      plasminogen nor plasminogen activators (PAs) alone affected dissociation;
      however, activation of plasminogen to plasmin by either urokinase PA or tissue
      type PA resulted in the dissociation of IGF-BP complexes. Plasmin dissociated
      immunoreactive and bioactive IGF from IGFBP equivalent to approximately 70% and
      approximately 60% of the acid control value, respectively. In medium conditioned
      by MG-63 cells, dissociation of IGF-BP complexes was catalyzed by PAs secreted by
      MG-63 cells, principally urokinase PA. Limited plasmin degradation of IGF was
      suggested by chromatographic experiments involving [125I] IGF. Treatment of
      uncomplexed IGF-I with plasmin concentrations equivalent to those in
      chromatographic experiments did not result in a significant loss of bioactivity,
      although a 2-fold increase in the plasmin concentration resulted in a
      approximately 20% loss of activity. Similar plasmin treatment of equimolar
      concentrations of hIGFBP-1 resulted in a marked degradation of IGFBP, with loss
      of IGF-binding ability. In vitro experiments confirmed plasmin dissociation of
      bioactive IGF-I from hIGFBP-1. In MG-63 cells, IGFBPs can form an IGF reservoir
      in the pericellular space surrounding the cells by combining IGFs with IGF-BP to
      form complexes that are incapable of binding to the IGF receptors. The secretion
      of PAs by osteosarcoma cells and the availability of plasminogen in the
      extravascular tissues indicate the possibility of a regulatory system in
      osteosarcoma cells in which pericellular plasmin affects the availability of IGFs
      to their membrane receptors.

PMID- 1371449
TI  - Gene expression of insulin-like growth factors (IGFs), the type 1 IGF receptor,
      and IGF-binding proteins in dexamethasone-induced fetal growth retardation.
AB  - Altered gene expression and/or actions of the insulin-like growth factors (IGFs)
      have been implicated in the mediation of both pre- and postnatal growth
      retardation secondary to glucocorticoid excess. To investigate this possibility,
      we assessed the gene expression of the IGFs, the type I IGF receptor, and IGF
      binding proteins (IGFBPs) in 20-day gestation liver and lung of growth-retarded
      fetuses whose mothers were treated with dexamethasone (DXM; 100 micrograms, ip,
      daily) on gestation days 15-19 (gestation = 21-22 days). DXM treatment in dams
      produced fetal growth retardation without decreasing litter size (32% decrease in
      fetal body weight). Both fetal liver and lung demonstrated decreased wet weight
      (48% and 47%, respectively) and DNA content (65% and 51%, respectively) compared
      to control animals. Our results suggest that increased expression of IGFBP-1, and
      possibly IGFBP-2, is involved in mediating the marked growth retardation. As
      assessed by solution hybridization assays and Northern blot analysis, there was
      an 8.5-fold increase in IGFBP-1 mRNA expression in the livers of DXM-treated
      fetal animals compared to that in sham-injected controls (P less than 0.002).
      IGFBP-2 mRNA expression was also increased (60%) in fetal liver, whereas IGFBP-3
      was decreased (57%). In fetal lung, IGFBP-1 transcript abundance was also higher
      in DXM-treated fetal animals. Serum concentrations of IGFBP-1, but not those of
      IGFBP-2, were increased (approximately 4-fold) in the DXM-treated fetuses, as
      quantified by [125I]IGF-I ligand blotting and IGFBP-2 immunoblotting. Because
      hypoinsulinemia increases the expression of IGFBP-1 and -2, serum insulin
      concentrations were measured and found to be decreased in the DXM-treated fetuses
      (24 microU/ml) compared to control values (72 microU/ml). Analysis of mRNA
      expression for IGF-I, IGF-II, and the type 1 receptor transcripts did not support
      a role for decreased IGF or IGF receptor expression in the etiology of DXM
      mediated growth retardation. IGF-I was unchanged in both liver and lung, and IGF
      II transcripts were increased by 31% in liver and unchanged in lung of DXM
      treated fetal animals. Northern analysis of hepatic and lung poly(A) RNA
      demonstrated no evidence for independent regulation of specific-sized IGF
      transcripts. Further, type 1 IGF receptor RNA abundance increased 42% in fetal
      liver and was unchanged in lung. Because IGFBPs may modulate IGF action, these
      results suggest that increased IGFBP-1, and possibly IGFBP-2, expression may be
      of importance in the etiology of DXM-induced fetal growth retardation.

PMID- 1371450
TI  - Effects of bombesin on pancreatic digestive enzyme gene expression.
AB  - We examined the effects of bombesin on rat pancreatic digestive enzyme gene
      expression using cloned complementary DNA probes for amylase, trypsinogen I,
      chymotrypsinogen B, and lysophospholipase. Rats were injected sc three times
      daily with 5 nmol/kg body wt bombesin. Pancreata were investigated after 6, 12,
      24, 48, and 120 h of hormone treatment. Bombesin administration resulted in a
      time-dependent increase of pancreatic weight, as well as DNA and protein
      concentration. Cellular hypertrophy became evident after 48 h, and pancreatic
      hyperplasia occurred after 5 days of hormone treatment. Bombesin administration
      resulted in a time-dependent parallel decrease of amylase and lysophospholipase
      messenger RNA (mRNA) concentrations with maximal inhibition occurring after 120 h
      of bombesin treatment (13 +/- 1% and 14 +/- 3% of control, respectively, P less
      than 0.05, n = 6). In contrast, chymotrypsin and trypsin mRNA levels remained
      unaltered after bombesin treatment for up to 5 days. Amylase and chymotrypsin
      enzyme levels did not correlate with their respective mRNA concentrations. Both
      decreased to approximately 50% of control after 12 h and increased to 126 +/- 38%
      of control and 388 +/- 109% of control (P less than 0.05, n = 6), respectively,
      after 5 days of bombesin treatment. To test whether the bombesin regulation was
      mediated by the release of cholecystokinin (CCK), the specific CCK receptor
      antagonist L-364,718 (1 mg/kg body wt) was injected ip either alone, or 15 min
      before each bombesin injection for 5 days. Although the antagonist alone
      significantly reduced the mRNA concentrations for trypsin, chymotrypsin, and
      lysophospholipase to approximately 50%, it did not block the effects of bombesin
      on pancreatic digestive enzyme levels. These data therefore indicate that
      bombesin regulates pancreatic digestive enzyme mRNA and protein concentrations in
      a nonparallel manner; furthermore, CCK is not involved in mediating the bombesin
      effects on pancreatic gene expression.

PMID- 1371452
TI  - Evidence for a negative ultrashort loop feedback regulating galanin release from
      the arcuate nucleus-median eminence functional unit.
AB  - Recent studies from our laboratory have demonstrated that galanin (GAL) is a
      member of the hypothalamic-hypophysiotropic hormone family. Most of the
      hypothalamic hormones regulate their own secretion rate by ultrashort loop
      feedback mechanisms. The purpose of these studies was to evaluate the possibility
      that hypothalamic GAL could regulate its own release through a similar mechanism.
      Galanin secretion from median eminence (ME) fragments incubated in vitro
      increased exponentially with time, whereas GAL release from arcuate nucleus-ME
      (AN-ME) fragments depicted a secretory profile consisting of an initial
      exponential rising phase, followed by a plateau phase in which GAL secretion was
      apparently abolished. Moreover, preexposure of AN-ME fragments to porcine GAL
      (pGAL) increased tissue responsiveness to K(+)-induced depolarization, suggesting
      that pGAL reduced the gain of the system. Thus, after pGAL removal, AN-ME
      fragments appear to be more sensitive to the depolarizing stimulus. In addition,
      blockade of GAL biological activity in vivo by administration of a sheep antirat
      GAL serum increased GAL release from AN-ME fragments in vitro, whereas this
      treatment did not affect GAL release from ME terminals. These results indicate
      that GAL neurons may diminish their own activity, establishing, therefore, a
      negative ultrashort loop feedback that controls the firing of the AN galaninergic
      network and maintains a balanced physiological status. By means of electron
      microscopy, we demonstrated that GAL-containing perikarya and proximal dendrites
      receive synapsing axons immunoreactive for the same peptide in the AN, which
      provides the anatomical basis for interactions between galaninergic neurons. In
      conclusion, our data support the notion that the galaninergic system, as other
      peptidergic neurotransmitters, is able to regulate its own release via a negative
      ultrashort loop feedback control mechanism that is operative at the level of the
      AN.

PMID- 1371451
TI  - Regulation of insulin-like growth factor-binding protein expression by thyroid
      hormone in rat GH3 pituitary tumor cells.
AB  - Rat pituitary GH3 tumor cells express GH and insulin-like growth factor-I (IGF-I)
      mRNAs and possess specific IGF-I and IGF-II receptors which mediate the
      inhibitory effect of IGF on GH secretion. T3 increases the rate of cell
      replication and GH gene transcription, and causes an increase in IGF-I binding to
      cell membranes. Since the IGFs circulate in association with specific binding
      proteins (IGFBPs) that appear to modulate the access of IGFs to their receptors,
      we have investigated the effect of T3 treatment on the expression of IGFBPs in
      GH3 cells. Cells were grown in serum-free defined medium, and IGFBP secretion was
      determined by Western ligand blotting of conditioned medium after the addition of
      T3 and/or various peptides for 48-72 h. The conditioned medium of GH3 cells
      revealed a complex of bands migrating at 40-45 Mr, a pattern typical of rat (r)
      IGFBP-3. T3 treatment resulted in an increase in rIGFBP-3. IGF-I, IGF-II, and
      insulin did not alter rIGFBP-3 levels. After concentrating (10-fold) conditioned
      medium samples, two additional bands at 24K and 28K mol wt were also seen. These
      bands corresponded in size to rIGFBP-4 (24K) and its glycosylated form (28K). The
      mRNAs for both rIGFBP-3 and rIGFBP-4 were present in GH3 cells; T3 treatment
      increased steady state levels of rIGFBP-3 mRNA, but did not affect BP-4 mRNA
      levels. To learn whether the increased expression of IGFBPs could be responsible
      for the increased IGF-I binding seen after T3 treatment, [125I]IGF-I was cross
      linked to GH3 membranes, and the proteins were separated on a 5-15% gradient
      sodium dodecyl sulfate-polyacrylamide gel under reducing conditions. T3 treatment
      induced a large increase in the intensity of bands migrating at 135K and 280K,
      representing the alpha-subunit of the IGF-I receptor and an incompletely reduced
      alpha-alpha-dimer, respectively. No membrane-associated IGFBPs were detected. In
      conclusion, GH3 cells express two IGFBPs, rIGFBP-3 and rIGFBP-4, which are
      differentially regulated by T3. The increased binding of IGF-I to GH3 cell
      membranes after T3 treatment indicates that thyroid hormone induces an up
      regulation of IGF-I receptors and that the increased IGF-I binding to GH3
      membranes is not due to increased expression of membrane-associated IGFBPs.

PMID- 1371453
TI  - Regulation of insulin-like growth factor-binding proteins in serum and lymph of
      lactating cows by somatotropin.
AB  - The insulin-like growth factors (IGF) circulate bound to specific high affinity
      binding proteins (IGFBPs) that modulate physiological responses to both IGF-I and
      IGF-II. Administration of bovine somatotropin (bST) to lactating cows has been
      shown to increase total serum levels of IGF-I; however, its effects on IGFBPs are
      unknown. Therefore, we determined the effects of bST on specific IGFBPs that are
      present in bovine serum and lymph. The results show that bovine serum contains
      IGFBPs with mol wt (Mr) estimates of 43,000, 39,000, 34,000, 29,000, and 24,000,
      as determined by ligand blotting. Using specific antisera, immunoblotting showed
      that the 43,000 and 39,000 Mr bands were IGFBP-3 and the 34,000 Mr band was IGFBP
      2. All five forms of IGFBP were also present in afferent mammary lymph. To
      determine the effect of bST, four cows were treated with bST (40 mg/day) or
      vehicle for 12-day periods using a cross-over design. The intensity of the IGFBP
      3 band increased 3.3 +/- 0.1-fold (mean +/- SE; P less than 0.01) by day 5 of bST
      treatment compared to that in controls. The intensity of the IGFBP-2 band
      decreased 3-fold. Serum levels of IGFBP-2, determined by RIA, decreased from 581
      +/- 62 ng/ml during the control period to 156 +/- 52 ng/ml by day 5 of bST
      treatment (P less than 0.01). IGFBP-2 levels remained low for the entire 12-day
      treatment interval and rose to control levels within 4 days after cessation of
      bST. Results of a second study demonstrated that the decrease in IGFBP-2
      concentrations in plasma observed during bST treatment (578 +/- 60 vs. 335 +/- 57
      ng/ml) was paralleled by a decrease in IGFBP-2 levels in afferent mammary lymph
      (274 +/- 24 vs. 147 +/- 22 ng/ml). In contrast, the increase in IGFBP-3 levels
      observed in plasma during bST treatment by ligand blot analysis was not observed
      in lymph. In summary, bST increased serum levels of IGFBP-3 and decreased serum
      concentrations of IGFBP-2, while only IGFBP-2 levels were decreased in mammary
      lymph. Further studies are needed to determine whether these differences reflect
      differences in transport across capillaries or local production of specific forms
      of IGFBP.

PMID- 1371454
TI  - Insulin stimulates the tyrosine phosphorylation of a 61-kilodalton protein in rat
      adipocytes.
AB  - Insulin stimulated the tyrosine phosphorylation of a 61-kilodalton (kDa) protein
      in rat adipocytes prelabeled for 2 h with [32P]orthophosphate. Tyrosine
      phosphorylation of this 61-kDa protein displayed very similar insulin
      concentration dependency to receptor autophosphorylation and tyrosine
      phosphorylation of a high molecular mass receptor substrate of 160 kDa.
      Phosphorylation of the 61-kDa protein was very rapid with maximum labeling
      attained at 30 sec, paralleling that of the other two proteins. Phosphoamino acid
      analysis revealed that each of the insulin-responsive phosphoproteins contained
      phosphoserine as well as phosphotyrosine, though the ratio of two phosphoamino
      acids recovered from each protein differed. The 61-kDa protein yielded relatively
      equal proportions of phosphoserine and phosphotyrosine. In contrast, the insulin
      receptor yielded relatively more label on phosphotyrosine than phosphoserine,
      whereas label incorporated into the 160-kDa protein was recovered primarily on
      phosphoserine. Cleveland peptide maps using either Staphylococcus aureus V8
      proteinase or chymotrypsin revealed no similarities between the 61-kDa protein
      and the other tyrosine phosphorylated proteins. With subcellular fractionation,
      the 160-kDa protein was found in equal proportions in the high speed pellet
      (100,000 g) and supernatant. The 61-kDa protein had a similar distribution to
      that of the 160-kDa protein but was also detected in the low speed pellet (10,000
      g). The insulin receptor was localized to the low speed pellet. In summary, rat
      adipocytes contain an insulin-dependent phosphotyrosyl protein of 61 kDa which is
      distinct from the more prominent high molecular mass receptor substrate. This 61
      kDa protein has characteristics consistent with it being a substrate for the
      insulin receptor tyrosine kinase.

PMID- 1371456
TI  - Report on the nomenclature of the IGF binding proteins.

PMID- 1371455
TI  - Effects of tachykinins on luteinizing hormone release in female rats: potent
      inhibitory action of neuropeptide K.
AB  - Tachykinins, a family of biologically active related peptides, are found in
      variable amounts in the rat hypothalamus. We assessed the effects of five
      tachykinins, substance P (SP), neurokinin A (NKA), neuropeptide K (NPK),
      neuropeptide gamma (NP gamma), and neurokinin B (NKB), on LH release in different
      experimental model systems in ovariectomized rats. In the first series of
      experiments rats were ovariectomized and implanted with permanent cannulae in the
      third cerebroventricle of the rat brain. Two weeks later, the effects of
      intracerebroventricular injection of 0.5 or 1.25 nm various tachykinins on LH
      release were studied. The results showed that whereas SP, NKA, and NKB were
      ineffective, and NP gamma was marginally effective, NPK produced a long-lasting
      suppression of LH release. NPK decreased LH release in a dose- and time-related
      fashion. Similarly, in the second series of experiments, whereas SP and NKA were
      inactive, NPK completely suppressed the LH surge induced by progesterone in
      estrogen-primed ovariectomized rats. In the third series of experiments we
      observed that NK-2 receptor agonist [Nle10]NKA4-10, and not NK-1 receptor agonist
      [Sar9,Met(O2)11]SP, suppressed both the release of LH in vivo and basal and KCl
      induced hypothalamic LHRH release in vitro. These results show that NPK is the
      most effective tachykinin in suppressing LH release, and the inhibitory response
      is mediated by hypothalamic NK-2 receptors. These findings are in accord with the
      hypothesis that NPK may serve as a hypothalamic inhibitory
      neurotransmitter/neuromodulator of LHRH secretion.

PMID- 1371457
TI  - Expression of messenger RNA for insulin-like growth factors and insulin-like
      growth factor binding proteins by experimental breast cancer and normal breast
      tissue in vivo.
AB  - We report the expression of insulin-like growth factors (IGFs) and their binding
      proteins (IGFBPs) by breast cancer cells and normal breast tissue in vivo. N
      nitrosomethyl-urea (NMU)-induced rat mammary tumors synthesize mRNAs for IGF-II
      and IGFBP-2, -3, and -4. In contrast, normal lactating breast contains only IGFBP
      2 and IGF-II messages; IGFBP-3 and -4 mRNAs are absent in this tissue. IGF-I and
      IGFBP-1 mRNAs are not expressed in either NMU tumors or in normal breast. This is
      the first report of in vivo expression of IGFBPs and IGF-II messages in breast
      tumors.

PMID- 1371458
TI  - Dtrk, a Drosophila gene related to the trk family of neurotrophin receptors,
      encodes a novel class of neural cell adhesion molecule.
AB  - We report the identification and molecular characterization of Dtrk, a Drosophila
      gene encoding a receptor tyrosine kinase highly related to the trk family of
      mammalian neurotrophin receptors. The product of the Dtrk gene, gp160Dtrk, is
      dynamically expressed during Drosophila embryogenesis in several areas of the
      developing nervous system, including neurons and fasciculating axons. gp160Dtrk
      has structural homology with neural cell adhesion molecules of the immunoglobulin
      superfamily and promotes cell adhesion in a homophilic, Ca2+ independent manner.
      More importantly, this adhesion process specifically activates its tyrosine
      protein kinase activity. These findings suggest that gp160Dtrk represents a new
      class of neural cell adhesion molecules that may regulate neuronal recognition
      and axonal guidance during the development of the Drosophila nervous system.

PMID- 1371459
TI  - Import of cytochrome c heme lyase into mitochondria: a novel pathway into the
      intermembrane space.
AB  - Cytochrome c heme lyase (CCHL) catalyses the covalent attachment of the heme
      group to apocytochrome c during its import into mitochondria. The enzyme is
      membrane-associated and is located within the intermembrane space. The precursor
      of CCHL synthesized in vitro was efficiently translocated into isolated
      mitochondria from Neurospora crassa. The imported CCHL, like the native protein,
      was correctly localized to the intermembrane space, where it was membrane-bound.
      As with the majority of mitochondrial precursor proteins, CCHL uses the MOM19-GIP
      receptor complex in the outer membrane for import. In contrast to proteins taking
      the general import route, CCHL was imported independently of both ATP-hydrolysis
      and an electrochemical potential as external energy sources. CCHL which lacks a
      cleavable signal sequence apparently does not traverse the inner membrane to
      reach the intermembrane space; rather, it translocates through the outer membrane
      only. Thus, CCHL represents an example of a novel, 'non-conservative' import
      pathway into the intermembrane space, thereby also showing that the import
      apparatus in the outer membrane acts separately from the import machinery in the
      inner membrane.

PMID- 1371460
TI  - Expression of factor X and its significance for the determination of
      paramyxovirus tropism in the chick embryo.
AB  - Enveloped animal viruses usually possess a surface glycoprotein which mediates
      fusion between the viral envelope and host cell membrane, hence enabling the
      initiation of infection, and its biosynthesis often involves post-translational
      endoproteolytic activation of the inactive precursor by a host cell protease(s).
      Therefore, the protease distribution in the host must be critical for determining
      the viral tropism. We previously isolated from chick embryo a cogent candidate
      endoprotease of this kind for paramyxovirus infection, and demonstrated its
      identity with factor X (FX), a vitamin K-dependent serine protease in the
      prothrombin family which, in general, is synthesized in the liver and circulates
      as one of the plasma proteases essential for blood clotting. Here, we examined FX
      expression with specific cDNA and antibody probes in a series of embryonic
      tissues. Many tissues other than the liver expressed the specific mRNA but, in
      most instances, the translation products remained inactive zymogen forms. The
      enzymatically active FXa was detectable only in the allantoic fluid and amniotic
      fluid, and virus spreading was strictly confined to the tissues in direct contact
      with these FXa-containing fluids. Thus, the ectopically expressed FXa is probably
      the major host determinant of paramyxovirus tropism in ovo.

PMID- 1371461
TI  - Expression of a constitutive form of calcium/calmodulin dependent protein kinase
      II leads to arrest of the cell cycle in G2.
AB  - Calcium/calmodulin dependent protein kinase II (CaMKII) is a multifunctional
      serine/threonine protein kinase. We have created a calcium/calmodulin independent
      form of this enzyme by truncation. Expression of this enzyme fragment in a rabbit
      reticulocyte lysate yields a constitutive enzyme with specific activity similar
      to the activated native enzyme. We have established mammalian cell lines that
      transiently express this constitutive enzyme using the glucocorticoid-inducible
      mouse mammary tumor virus long terminal repeat. The transient increase in kinase
      activity results in a complete cessation of cell cycle progression. This block
      develops as a consequence of a specific arrest of the cell cycle in G2. During
      the block, increases in histone H1 kinase activity present in p13 beads or anti
      cdc2 immunoprecipitates are seen in parallel with the accumulation of cells at
      G2, arguing that the arrest is not due to a failure to activate cdc2 as a histone
      H1 kinase. These results suggest that other changes in serine/threonine protein
      phosphorylation besides those involved in activation of cdc2 as a histone H1
      kinase may be necessary for proper G2-M transition.

PMID- 1371462
TI  - Thyroid expression of an A2 adenosine receptor transgene induces thyroid
      hyperplasia and hyperthyroidism.
AB  - Cyclic AMP (cAMP) is the major intracellular second messenger of thyrotropin
      (TSH) action on thyroid cells. It stimulates growth as well as the function and
      differentiation of cultured thyrocytes. The adenosine A2 receptor, which
      activates adenylyl cyclase via coupling to the stimulating G protein (Gs), has
      been shown to promote constitutive activation of the cAMP cascade when
      transfected into various cell types. In order to test whether the A2 receptor was
      able to function similarly in vivo and to investigate the possible consequences
      of permanent adenylyl cyclase activation in thyroid cells, lines of transgenic
      mice were generated expressing the canine A2 adenosine receptor under control of
      the bovine thyroglobulin gene promoter. Thyroid-specific expression of the A2
      adenosine receptor transgene promoted gland hyperplasia and severe
      hyperthyroidism causing premature death of the animals. The resulting goitre
      represents a model of hyperfunctioning adenomas: it demonstrates that
      constitutive activation of the cAMP cascade in such differentiated epithelial
      cells is sufficient to stimulate autonomous and uncontrolled function and growth.

PMID- 1371465
TI  - Clinical recognition of patients affected by a peroxisomal disorder: a
      retrospective study in 40 patients.
AB  - Peroxisomal disorders are genetic diseases in which an impairment in one or more
      peroxisomal function(s) causes clinical and multiple biochemical abnormalities.
      Early recognition of the major peroxisomal disorders in which functional
      peroxisomes are virtually absent, leading to a generalised impairment of
      peroxisomal functions, is of utmost importance, as this will enable the prenatal
      diagnosis of these severe diseases in future pregnancies. Unfortunately, clinical
      recognition of these disorders can be difficult because of the aspecific and
      varying phenotypic presentation. We analysed the clinical characteristics in 40
      patients suspected of having a peroxisomal disorder to identify specific clinical
      criteria for diagnosis. From this study we conclude that the combined presence of
      at least three major clinical characteristics (present in greater than 75% of the
      affected patients, including psychomotor retardation, hypotonia, impaired
      hearing, low/broad nasal bridge, abnormal ERG, hepatomegaly) and one or more
      minor characteristics (present in 50%-75% of the patients, like large
      fontanelles, shallow orbital ridges, epicanthus, anteverted nostrils, retinitis
      pigmentosa) warrants biochemical investigation of peroxisomal functions. Further
      prospective investigations will have to be done to evaluate these criteria.

PMID- 1371463
TI  - Activation of extracellular signal-regulated kinase, ERK2, by p21ras oncoprotein.
AB  - To examine signal transduction events activated by oncogenic p21ras, we have
      studied kinases that are activated following the scrape loading of p21ras into
      quiescent cells. We observe rapid activation of 42 kDa and 46 kDa protein
      kinases. The 42 kDa kinase is the mitogen and extracellular-signal regulated
      kinase ERK2, (MAP2 kinase), which is activated by phosphorylation on tyrosine and
      threonine in response to oncogenic p21ras, while the 46 kDa kinase is likely to
      be another member of the ERK family. Stimulation of these kinases by oncogenic
      p21ras does not require the presence of growth factors, showing that oncogenic
      p21ras uncouples kinase activation from external signals. In ras transformed cell
      lines, these kinases are constitutively activated. We propose that the kinases
      are important components of the signal transduction pathway activated by p21ras
      oncoprotein.

PMID- 1371466
TI  - Human milk T lymphocytes are mostly HML-1-positive cells.

PMID- 1371464
TI  - Dysregulation of gene expression in mouse trisomy 16, an animal model of Down
      syndrome.
AB  - In humans, trisomy 21 results in a specific phenotype known as Down syndrome
      (DS). The mechanism by which an extra copy of normal genes leads to the DS
      phenotype is unknown. Most studies in DS and other aneuploid organisms have shown
      that gene dose is proportional to gene expression. To date, most genes examined
      have encoded either metabolic enzymes or constitutively expressed products. In
      the trisomy 16 mouse, an animal model of DS, we found marked dysregulation of two
      developmentally regulated genes, App and Prn-p. Dysregulation varied from tissue
      to tissue and during development in the same tissue. We conclude that abnormal
      phenotypes seen in aneuploid conditions may result in part from disordered
      expression of developmentally regulated genes.

PMID- 1371467
TI  - A major human thyroglobulin epitope defined with monoclonal antibodies is mainly
      recognized by human autoantibodies.
AB  - The antigenic nature of 15 anti-human thyroglobulin (hTg) monoclonal antibody
      (mAb) epitopes was studied by two different approaches. First, we tested two
      successive protease-digest products of hTg. Only four mAb from the same cluster
      of reactivity recognized a low-molecular weight peptide, the other mAb only bound
      native hTg or high-molecular weight digest fractions. Second, these 15 mAb were
      used to immunoscreen hTg expression libraries. Only the same four mAb revealed
      immunoreactive clones corresponding to region 1149-1295 on the hTg primary
      sequence. After subcloning, this antigenic determinant was reduced to a 102-amino
      acid peptide (hTg region 1149-1250). The two different methodologies were
      coherent and complementary, and demonstrated that hTg sequence 1149-1250 is the
      target for this cluster of four mAb. Moreover, anti-hTg autoantibodies which
      cross-reacted with these mAb bound the 102-amino acid peptide. This epitope was
      the one most frequently detected by sera from autoimmune thyroid disease. The
      data confirm the presence of an immunodominant domain in the central part of the
      hTg molecule and suggest that this mAb epitope may be a powerful probe for the
      diagnosis of autoimmune thyroid disorders.

PMID- 1371468
TI  - Characterization of the bovine peripheral lymph node homing receptor: a lectin
      cell adhesion molecule (LECAM).
AB  - The phenomenon of tissue-specific homing of lymphocyte populations has been most
      clearly shown in larger domestic animals, such as the sheep and cow, yet the
      molecular interactions which control these processes in these animals have not
      been defined. Here we tested the cross-reactivity of four anti-human peripheral
      lymph node homing receptor (LECAM-1) (also known as LAM-1, LEC-CAM-1, Leu-8, TQ
      1, or human equivalent of gp90 MEL-14) antibodies on bovine lymphocytes. These
      antibodies stained all bovine neutrophils and monocytes, and variable numbers of
      peripheral blood lymphocytes, as determined by flow cytometry. In young calves
      (less than 1 month old) virtually all circulating lymphocytes expressed LECAM-1,
      whereas the percentage of positive lymphocytes in older animals (greater than 1
      year) varied from 17%-67%. Bovine LECAM-1 was rapidly lost from the cell surface
      of PMA-activated and chymotrypsin-treated cells. Anti-LECAM-1 monoclonal antibody
      blocked greater than 80% of bovine lymphocyte binding to peripheral lymph node
      high endothelial venules (HEV). Since the lectin domain of LECAM-1 is thought to
      mediate lymphocyte-HEV adhesion, we sought to establish further the similarity of
      the bovine, mouse, and human molecules by comparing nucleotide sequences in this
      region of the molecule. The polymerase chain reaction (PCR) was used to
      specifically clone the bovine lectin domain from single-strand cDNA. Subsequent
      sequencing showed an identity of greater than 80% at the nucleotide level with
      the human and mouse molecules. The predicted amino acid sequences were also
      highly conserved. Though striking similarities were seen between the bovine,
      mouse and human molecule, indicating evolutionary conservation of this family of
      proteins, notable differences were detected. The nucleotide sequence of the
      bovine lectin domain predicts one additional N-linked glycosylation site compared
      to mouse and human. Preliminary analysis suggested a more tissue-restricted
      expression of LECAM-1 in the compared to the human and mouse, which correlates
      with a better separation of lymphocyte homing phenotypes seen in these larger
      animals. Virtually all peripheral lymph node lymphocytes in 6-month-old calves
      expressed LECAM-1, whereas, ileal Peyer's patch lymphocytes were predominantly
      negative. Finally, by testing anti-human LECAM-1 antibodies in a different
      species we have established the co-expression of antigenic epitopes on leucocyte
      LECAM-1 and a molecule(s) expressed by endothelial cells.

PMID- 1371469
TI  - Mouse autoreactive gamma/delta T cells. I. Functional properties of autoreactive
      T cell hybridomas.
AB  - A minor population of dendritic epidermal T cells (DETC) express the V gamma 1.1C
      gamma 4V delta 6 T cell receptor and T cell clones and hybridomas derived from
      this subset constitutively secrete cytokines in culture secondary to recognition
      of an autoantigen. Activation of these autoreactive cells requires the use of the
      vitronection receptor (VNR) as an accessory molecule which interacts with the Arg
      Gly-Asp-Ser (RGDS) sequence of extracellular matrix (ECM) proteins. We have
      compared the functional properties of C gamma 4+ hybridomas derived from newborn
      thymocytes and from adult spleen with the DETC hybridomas/lines in terms of their
      ability to secrete cytokines spontaneously and for the use of the VNR as an
      accessory molecule. Almost all the C gamma 4+ thymocyte hybridomas secreted
      cytokines spontaneously and in the majority of lines the most prominent cytokine
      secreted was granulocyte-monocyte colony-stimulating factor. In contrast, none of
      the four splenic C gamma 4+ hybridomas secreted cytokines spontaneously although
      all were capable of cytokine production following activation via the T cell
      receptor. Although the thymocyte hybridomas did not grow as adherent cell lines
      in culture, constitutive cytokine production required engagement of the VNR by
      its ligand in ECM proteins. In all cases, cytokine production could be inhibited
      by an anti-VNR monoclonal antibody as well as by soluble RGDS. The strong
      correlation of functional and molecular properties between thymocyte C gamma 4+
      hybridomas and C gamma 4+ DETC suggests that the C gamma 4+ DETC may be of thymic
      origin and that cells with potential for autoreactivity residing in the thymus at
      birth may populate other peripheral locations in the mouse. The data also support
      the concept that the VNR, and possibly other integrins, play a role as accessory
      elements for autoreactive cells and may be essential for the regulation of such
      activity.

PMID- 1371470
TI  - Inhibitory activity against sporozoites induced by antibodies directed against
      nonrepetitive regions of the circumsporozoite protein of Plasmodium vivax.
AB  - In previous studies, Saimiri sciureus boliviensis monkeys have been immunized
      with four recombinant proteins reproducing part of the circumsporozoite (CS)
      protein of Plasmodium vivax sporozoites (NS1(81) V20, rPvCS-1, rPvCS-2, rPv-CS
      3), or with irradiated sporozoites of P. vivax Salvador I strain. To analyze the
      antibody response elicited against epitopes located outside the immunodominant
      repeat region of the CS protein, serum samples from these animals were tested for
      their ability to inhibit the in vitro development of liver stages of P. vivax
      VK247 strain, characterized from the other strains only by a specific repeat
      region on the CS protein. Results indicated that there is at least one protective
      B-cell epitope outside the repeat region of the CS protein of P. vivax
      sporozoites, and that this epitope can be expressed by irradiated sporozoites,
      rPvCS-1 and -3, but not by rPvCS-1 or NS1(81)V20. Therefore, we designed peptides
      from the amino acid sequences present both in rPvCS-2 and -3, but not included in
      the recombinant proteins rPvCS-1 and NS1(81)V20. Anti-peptide antibodies had no
      activity on the development of sporozoites of P. vivax Salvador I strain, into
      schizonts in primary culture of Saimiri monkey hepatocytes. In addition,
      antisporozoite antibodies did not react with any of the peptides. These results
      suggest that the in vitro inhibition observed in this study could depend upon the
      conformation of the CS protein. This study also demonstrates that antibody
      response to unnatural linear epitopes can be induced by immunization with
      recombinant proteins.

PMID- 1371471
TI  - CD45 modulates T cell receptor/CD3-induced activation of human thymocytes via
      regulation of tyrosine phosphorylation.
AB  - Stimulation of thymocytes or mature T cells via the T cell receptor (TcR)/CD3
      complex activates a cascade of processes inducing cells to enter the cell cycle.
      A key step is the activation of phosphatidylinositol-specific phospholipase C (PI
      PLC) within seconds following TcR/CD3 stimulation, an event which is strongly
      enhanced by co-ligation of the CD4 (or CD8) accessory molecule with TcR/CD3. In
      contrast, co-ligation of CD45 inhibits the same TcR/CD3 responses. The machinery
      which couples the TcR/CD3 complex, CD4, and CD45 to PI-PLC appears to involve
      regulation of tyrosine phosphorylation, as the TcR/CD3 and CD4 receptors are
      associated with the tyrosine kinases p59fyn and p56lck, respectively, and CD45
      has intrinsic tyrosine phosphatase activity. Here, we have examined the ability
      of CD45 to regulate signal transduction via TcR/CD3 in human thymocytes. Co-cross
      linking CD45 to the TcR/CD3 complex strongly suppressed the tyrosine
      phosphorylation of several intracellular substrates normally seen following
      TcR/CD3 stimulation. This effect of CD45 was associated with inhibition of a rise
      in intracellular calcium following TcR/CD3 ligation. Since TcR/CD3 stimulation of
      mature T cells induces tyrosine phosphorylation of PLC gamma 1, we investigated
      this phenomenon in thymocytes, and asked whether ligation of CD45 might regulate
      this process. By immunoprecipitation we found that TcR/CD3 stimulation induced
      tyrosine phosphorylation of PLC gamma 1, an effect which was enhanced by co-cross
      linking CD4 to TcR/CD3. In contrast, co-ligation of CD45 strongly blocked PLC
      gamma 1 phosphorylation induced by either stimulus. Consistent with previous
      findings in mature T cells, CD45 cross-linking was able to partially inhibit
      TcR/CD3-induced thymocyte proliferation when interleukin 2 was used as a second
      signal, but almost completely (80%-90%) blocked proliferation when anti-CD28 mAb
      was used as the second signal, suggesting that CD45 cross-linking may be able to
      block interleukin 2 production via the CD28 pathway. These effects of CD45 on
      TcR/CD3 signaling and proliferation in thymocytes point towards a potential role
      for this pathway in thymic selection.

PMID- 1371472
TI  - T cell receptor diversity and activation markers in the V delta 1 subset of
      rheumatoid synovial fluid and peripheral blood T lymphocytes.
AB  - In the present study we have characterized the gamma/delta T cell receptor (TcR)
      population in synovial fluid (SF) and peripheral blood (PB) of patients with
      chronic inflammatory arthritis. By double staining we have shown that (a)
      synovial V delta 1+ cells have a high expression of activation markers CD45R0
      ("memory cells") and HLA-DR as compared to PB, indicating a preactivated
      population of V delta 1-carrying T cells in vivo and (b) interleukin 2-induced
      expansion of synovial cells yields a high proportion of gamma/delta in most
      samples expressing predominantly the V delta 1 TcR. Junctional sequence analysis
      of the TcR delta chain from interleukin 2-expanded PB cell lines demonstrated a
      polyclonal V delta 1 population in three out of three samples. In SF cell lines
      three out of four samples were polyclonally expanded. In SF from one patient,
      however, a limited repertoire of expressed V delta 1 genes was found. Altogether,
      our data demonstrate the presence of preactivated V delta 1-expressing cells in
      the synovial compartment. This V delta 1 population is predominantly polyclonal,
      except in one patient where oligoclonally expanded V delta 1 cells were detected.

PMID- 1371473
TI  - Characterization of rat encephalitogenic T cells bearing non-V beta 8 T cell
      receptors.
AB  - In this study, we demonstrate that T cell lines specific for a synthetic peptide
      representing sequence 87 to 99 of myelin basic protein (MBP) are encephalitogenic
      in Lewis rats. However, unlike syngeneic T cells specific for MBP residues 68 to
      88 which exclusively use V beta 8 in their antigen receptors, these cells do not.
      None of the 10 T cell lines and T hybridomas specific for MBP (87-99) used V beta
      8 in their T cell receptors. Our results document for the first time that rat
      encephalitogenic T cells do not exclusively use V beta 8 in T cell receptors that
      rat encephalitogenic T cells specific for MBP (87-99) are heterogeneous and that
      MBP (87-99) contains at least two epitopes for rat T cells.

PMID- 1371474
TI  - Activation of natural killer cells via the Fc gamma RIII (CD16) requires initial
      tyrosine phosphorylation.
AB  - Triggering of the Fc gamma RIII (CD16) on natural killer (NK) cells by monoclonal
      antibodies or antibody-coated target cells stimulates a rapid phospholipase C
      (PLC)-mediated hydrolysis of inositol phospholipids and results in subsequent
      delivery of the lytic hit. The role of initial tyrosine phosphorylation in these
      events was investigated with a tyrosine protein kinase (TPK) inhibitor,
      genistein. At doses that inhibited CD16-triggered tyrosine phosphorylation of
      substrates in intact cells, genistein did not influence serine/threonine
      phosphorylation or target cell binding but prevented PLC activation, cell
      mediated cytotoxicity and antibody-dependent cellular cytotoxicity. These
      findings indicate that tyrosine phosphorylation is an early and critical event
      during receptor-mediated activation of the lytic machinery.

PMID- 1371475
TI  - Intracellular Ca2+ release by flufenamic acid and other blockers of the non
      selective cation channel.
AB  - We report in this paper using measurement of intracellular free Ca2+ with fura-2,
      that flufenamic acid and several related blockers of the 25 pS Ca(2+)-activated
      non-selective cation channel cause release of Ca2+ from an intracellular store
      other than the endoplasmic reticulum, possibly from mitochondria. A new compound,
      4'-methyl-DPC, is found to be as effective in blocking non-selective cation
      channels as other flufenamate analogs but, like the parent compound, the non
      selective cation channel blocker DPC, it does not cause release of Ca2+ from
      intracellular stores. DPC and 4'-methyl-DPC are thus the most suitable of the
      available blockers of non-selective cation channels for use in studies on the
      role of these channels in normal cell function.

PMID- 1371476
TI  - Imidazole-SDS-Zn reverse staining of proteins in gels containing or not SDS and
      microsequence of individual unmodified electroblotted proteins.
AB  - A reverse staining procedure is described for the detection of proteins in
      acrylamide and agarose gels with and without SDS. Protein detection occurs a few
      minutes after electrophoresis. The sensitivity on acrylamide gels is higher than
      that of Coomassie blue staining either on acrylamide gels or on
      electrotransferred membranes. Sequencing of protein bands only detected by
      reverse staining on the gel and not by Coomassie blue is demonstrated.

PMID- 1371477
TI  - Transcription mapping of the Ori L region reveals novel precursors of mature RNA
      species and antisense RNAs in rat mitochondrial genome.
AB  - We have identified new transcripts in the region surrounding the L-strand
      replication origin (Ori L) of rat liver mitochondrial DNA. In particular, we have
      detected previously unidentified intermediates of RNA processing on both the
      heavy and the light strands, such as precursors of the ND2 mRNA plus the Trp-tRNA
      and precursors of the tRNAs clustered in the Ori L region. This indicates that
      the mechanism of RNA processing in mitochondria proceeds step-wise producing a
      variety of precursors of the mature forms. The other striking finding is the
      detection of antisense RNA species in the region of L-strand replication. Since a
      variety of antisense transcripts were also found in the D-loop region of rat
      mitochondrial DNA, we suggest that they might play a regulatory role in the
      replication and expression of the mitochondrial genome.

PMID- 1371478
TI  - A depolarization can trigger Ca2+ uptake and the acrosome reaction when preceded
      by a hyperpolarization in L. pictus sea urchin sperm.
AB  - The acrosome reaction (AR) is an exocytotic event that allows sperm to recognize
      and fuse with the egg. In the sea urchin sperm this reaction is triggered by the
      outer investment of the egg, the jelly, which induces ionic movements leading to
      increases in intracellular Ca2+ ([Ca2+]i) and intracellular pH (pHi), a K(+)
      dependent transient hyperpolarization which may involve K+ channels, and a
      depolarization which depends on external Ca2+. The present paper explores the
      role of the hyperpolarization in the triggering of the acrosome reaction. The
      artificial hyperpolarization of Lytechinus pictus sperm with valinomycin in K(+)
      free seawater raised the pHi, caused a small increase in 45Ca2+ uptake, and
      triggered some AR. When the cells were depolarized with KCl (30 mM) 40-60 sec
      after the induced hyperpolarization, the pHi decreased and there was a
      significant increase in 45Ca2+ uptake, [Ca2+]i, and the AR. This waiting time was
      necessary in order to allow the pHi change required for the AR to occur. Thus,
      the jelly-induced hyperpolarization may lead to the intracellular alkalinization
      required to trigger the AR, and, on its own or via pHi, may regulate Ca2+
      transport systems involved in this process. Because of the key role played by K+
      in the triggering of the AR, the presence and characteristics of ion channels in
      L. pictus isolated sperm plasma membranes are being explored. Planar lipid
      bilayers into which these membranes were incorporated by fusion displayed 85 pS
      single channel transitions which were cation selective.

PMID- 1371479
TI  - An investigation of the specification of unequal cleavages in leech embryos.
AB  - Leech embryos develop via stereotyped cell divisions, many of which are unequal.
      The first division generates identifiable cells, blastomeres AB and CD, which
      normally follow distinct developmental pathways. When these two cells are
      dissociated and cultured in isolation, their fates remain distinct and are
      reminiscent of normal development, but their typical cleavage patterns are
      disrupted; cell AB undergoes relatively few cell divisions, giving rise to a
      variable number of macromeres and micromeres, while cell CD cleaves many times,
      usually forming a poorly organized set of macromeres, embryonic stem cells
      (teloblasts), and micromeres. We have investigated the hypothesis that the
      abnormal cleavage pattern of isolated CD blastomeres is due to removal of
      mechanical constraints normally imposed by cell AB. We find that when cell CD is
      constrained in vitro to mimic its in vivo shape, it cleaves more normally.

PMID- 1371480
TI  - Mechanism of skin morphogenesis. I. Analyses with antibodies to adhesion
      molecules tenascin, N-CAM, and integrin.
AB  - To understand cell interactions during induction of skin appendages, we studied
      the roles of adhesion molecules N-CAM, tenascin, integrin, and fibronectin during
      feather development. Tenascin appeared in a periodic pattern on epithelia and was
      so far the earliest molecule detected in placodes. Three placode domains were
      identified: the anterior was positive for tenascin, the distal positive for N
      CAM, and the posterior lacking both. Integrin appeared in dermal-epidermal
      junctions of placodes. In feather buds, sagittal sections revealed a transient
      anterior-posterior asymmetry with tenascin and N-CAM enriched in the anterior
      mesoderm. Tangential sections revealed a lateral-medial asymmetry with tenascin
      distributed in a ring shape and N-CAM in an "X" shape. Integrin was diffusely
      distributed within buds. Later tenascin and N-CAM were enriched in dermal
      papilla, the inducer of skin appendages. Perturbation of embryonic skin explant
      cultures with antibodies showed that anti-integrin beta 1 and anti-fibronectin
      blocked epithelial-mesenchymal interaction, anti-N-CAM caused uneven segregation
      of mesenchymal condensation, and anti-tenascin inhibited feather bud elongation.
      Dose-response curves showed gradual effects by these antibodies. The results
      indicated that these adhesion molecules are independently regulated and each
      contributes in different phases during morphogenesis of skin appendages.

PMID- 1371481
TI  - Structural and developmental analysis of two linked myosin heavy chain genes.
AB  - We have identified at the molecular level two murine myosin heavy chain (MHC)
      genes which encode adult skeletal isoforms. As is the case for the murine cardiac
      MHC genes, the genes are closely linked, head to tail. To identify the isoform
      encoded by each gene, we located and sequenced the 3' termini and assessed the
      genes' temporal and tissue-specific expression patterns using probes specific for
      the 3' untranslated regions. These analyses indicate that the myosin encoded by
      the gene located 5' in the linked pair is the murine 2A isoform. The isoform
      encoded by the 3'-most gene of the linked pair appears to encode an additional
      isoform that is expressed in a number of adult skeletal muscles. The pattern of
      expression of the 3'-most gene indicates that it is tightly controlled
      developmentally. Transcripts from this gene, when compared to those from the
      MHC2A and beta-MHC genes, are the predominant MHC transcripts found in the
      diaphragm, tongue, soleus, and masseter, indicating that it encodes a major
      skeletal MHC isoform.

PMID- 1371482
TI  - Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in
      primary culture.
AB  - The expression of several forms of cytochrome P450 including P450 1A2, 2D6, 2E1,
      and 3A was investigated in human hepatocytes maintained in primary culture for 96
      h in the absence or presence of 50 microM of various imidazole derivatives. These
      included ketoconazole, clotrimazole, miconazole, fluconazole, secnidazole and
      metronidazole. In addition, the typical inducers rifampicin and beta
      naphthoflavone were used for comparison. Western and Northern blot analysis of
      microsomes and RNA prepared from these cultures as well as de novo synthesis
      experiments revealed that, among the imidazole derivatives tested, only
      clotrimazole was a strong rifampicin-like inducer of P450 3A. The expression of
      the other forms of P450 tested was not affected by the treatments. Analysis of
      the inhibition of 13 monoxygenase activities, including ethoxyresorufin and
      phenacetin O-deethylases, coumarin 7 alpha-, lauric acid 11- and 12-, mephenytoin
      4-, debrisoquin 4-, and aniline hydroxylases, benzphetamine, aminopyrine,
      mephenytoin and erythromycin demethylases, and cyclosporin oxidase
      (representative of 10 different forms of P450 in human liver microsomes) revealed
      that ketoconazole was a strong and selective in vitro inhibitor of P450 3A
      (cyclosporin oxidase) with a Ki less than 1 microM. Clotrimazole and miconazole
      were also strong inhibitors of P450 3A-mediated activities in contrast to the
      other imidazole derivatives.

PMID- 1371483
TI  - [Cirrhosis, dysplasia and hepatocarcinoma. What are the practical consequences?].

PMID- 1371484
TI  - Ruthenium red delays the onset of cell death during oxidative stress of rat
      hepatocytes.
AB  - Our objective was to determine if ruthenium red protects against lethal oxidative
      injury of rat hepatocytes. tert-Butyl hydroperoxide, 100 mumol/L, was used to
      produce oxidative stress. After 2 hours of oxidative stress, cell viability was
      greater with than without 25 mumol/L ruthenium red (37% vs. 4.6%; P less than
      0.01). Despite this cytoprotection, ruthenium red did not alter the rate or
      extent of glutathione depletion, malondialdehyde generation, or adenosine
      triphosphate depletion. In contrast, ruthenium red did retard loss of the
      mitochondrial membrane potential (78% vs. 42% within 30 minutes; P less than
      0.01). However, the protective effect of ruthenium red could not solely be
      explained by preserving the mitochondrial membrane potential. Indeed, ruthenium
      red still improved cell survival after 2 hours of exposure to 10 mumol/L carbonyl
      cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler (39% vs. 13%; P
      less than 0.01). Cytosolic free calcium values did not change during the
      uncoupling of mitochondria, suggesting that the cytoprotective properties of
      ruthenium red cannot be explained by blocking mitochondrial calcium transport.
      Ruthenium red did inhibit proteolysis after 2 hours of exposure to tert-butyl
      hydroperoxide (434 +/- 62 vs. 242 +/- 20 nmol/10(6) cells; P = 0.016) or CCCP
      (236 +/- 50 vs. 99 +/- 38 nmol/10(6) cells; P = 0.04). The results indicate that
      ruthenium red appears to protect against hepatocellular injury by inhibiting
      degradative proteolytic activity. It is concluded that proteolysis may be an
      important mechanism contributing to lethal oxidative injury of hepatocytes.

PMID- 1371486
TI  - Hepatocellular carcinoma in transgenic mice: a consequence of continued
      expression of the HBx gene?

PMID- 1371485
TI  - Nucleotide sequences of 5-1-1 of hepatitis C virus in patients with chronic liver
      disease.
AB  - The discovery of hepatitis C virus (HCV) has led to the development of an assay
      against a viral peptide (C100-3), which is now used worldwide. It has been shown
      that the majority of HCV-infected individuals are positive for the antibody.
      However, there are patients who are repeatedly seronegative for the antibody
      despite the presence of HCV RNA in the serum. The nucleotide sequences of 5-1-1
      (a major epitope of C100-3) obtained from five antibody-positive patients and
      five negative patients with chronic liver disease were studied. The nucleotide
      identities of the seropositive and seronegative patients with HCV prototype
      sequence were 80.6% and 81.8%, respectively, not showing much difference in the
      nucleotide sequence of the 5-1-1 region. Moreover, no marked differences were
      noted in the deduced amino acid residues and the hydropathy profiles between the
      two groups. These data suggest that absence of the antibody in HCV carriers are
      not due to variations of major epitopes but are probably due to immunological
      incompetence against the synthetic C100-3 peptide.

PMID- 1371487
TI  - The ontogeny and distribution of neuropeptides in the human fetal and infant
      esophagus.
AB  - The innervation and neuropeptide expression of fetal and infant human esophagus
      were studied. Esophageal samples (n = 30) from 8 weeks' gestation to 28 months of
      age were immunostained using antisera to general and specific neuronal antigens,
      and the results were quantified using computer-assisted image analysis. Nerve
      protein (protein gene peptide 9.5 and synaptophysin) and glial cell protein
      (S100) immunoreactivities were present by 8 weeks' gestation in primitive cell
      bodies and fibers in the outer layers of the esophagus. Immunoreactivity for
      peptides was first detected in fibers at 11 weeks' gestation in myenteric plexus
      and at 13 weeks' gestation in muscle. Peptide-immunoreactive cell bodies were not
      seen until 13-15 weeks. A pattern of immunoreactivity for neuropeptides
      comparable with that seen in mature neonates and infants was present by 22 weeks
      of gestational age. The percentage area of protein gene peptide 9.5
      immunoreactive and vasoactive intestinal peptide-immunoreactive nerve fibers
      increased from low levels to 3.68% and 0.27%, respectively, at 13 weeks and
      peaked at 18 weeks (10.50% and 4.74%). These findings provide a foundation for
      future research into the contribution of neuropeptides to pediatric esophageal
      dysmotility.

PMID- 1371488
TI  - Hepatitis B virus envelope epitopes: gene assembly and expression in Escherichia
      coli of an immunologically reactive novel multiple-epitope polypeptide 1 (MEP-1).
AB  - A novel synthetic 323-bp gene with the open reading frame of a multiple-epitope
      polypeptide has been assembled and cloned. The gene is engineered by contiguous
      alignment of selected epitopes and functional domains of the hepatitis B virus
      envelope proteins separated by pairs of glycine residues. High-level bacterial
      production of this 100-amino acid (approx. 10 kDa) protein has been achieved and
      the gene product is stable. ELISA and Western blot experiments using epitope
      specific antisera confirm that the corresponding epitopes are present in the
      engineered protein.

PMID- 1371489
TI  - Isolation and characterization of a human gene that encodes a new subclass of
      protein tyrosine kinases.
AB  - We describe the isolation and cDNA sequence of a novel human gene, which is
      distinct from all known members of the human src family of proto-oncogenes. In
      contrast to these, an autophosphorylation site corresponding to Tyr416, as well
      as the equivalent of Tyr527 in p60c-src, are missing in the amino acid (aa)
      sequence deduced from this gene. Furthermore, no N-terminal myristylation site is
      found. Our human clone is 98% identical at the aa level to a gene which was
      isolated independently from neonatal rat brain and was termed csk for c-src
      kinase. We, therefore, propose to designate the present human gene CSK. In
      Northern blot experiments, CSK was found to be expressed in human lung and
      macrophages. Due to its extreme conservation across species barriers, the CSK
      product is likely to exert important regulatory functions. On the basis of its
      expression in tissues, not typically expressing high c-src levels, it can be
      assumed that its regulatory role is more general and may also involve other
      tyrosine kinases.

PMID- 1371490
TI  - Prevention of post-ischemic brain lipid conjugated diene production and
      neurological injury by hydroxyethyl starch-conjugated deferoxamine.
AB  - Hydroxyethyl starch conjugated deferoxamine (DFO) was administered to rats
      following resuscitation from 6.5 min cardiac arrest (CA) in an attempt to prevent
      the iron-catalyzed production of oxygen free radicals which may lead to
      neurologic injury and ultimately death following restoration of spontaneous
      circulation (ROSC). Brain conjugated dienes were analyzed spectrophotometrically
      4 and 24 hr following ROSC, and were found to be significantly elevated when
      compared to non-ischemic controls. Hydroxyethyl starch-DFO treated rats
      demonstrated no increased conjugated diene production at either period.
      Neurologic injury was significantly less in drug treated rats surviving 24 or 72
      hours when compared to controls. While mortality was similar in drug treated or
      control rats for the first 24 hours following ROSC, delayed mortality (days 1-10)
      was significantly less in drug treated animals, presumably as a result of
      neurologic protection afforded by post-ischemic drug administration.
      Administration of DFO conjugated to hydroxyethyl starch appears to modulate the
      neurologic injury which occurs during brain ischemia and reperfusion.

PMID- 1371491
TI  - Effects of FK506 and cyclosporin A on cytokine production studied in vitro at a
      single-cell level.
AB  - Mononuclear cells obtained from human blood were mitogen or antigen activated in
      vitro in the presence or absence of FK506 or cyclosporin A (CsA). Cytokine
      production was studied at a single-cell level by ultraviolet (UV) microscopy of
      fixed permeabilized cells using cytokine-specific monoclonal antibodies (mAb).
      Phenotypic characterization of the monokine-producing cells was achieved by two
      colour immunofluorescent staining. Cytokine production after antigen activation
      with Staphylococcus aureus enterotoxin A (SEA) was significantly reduced. FK506
      or CsA inhibited SEA-induced tumour necrosis factor-alpha (TNF-alpha) production
      both in monocytes (P less than 0.01) and in lymphocytes (P less than 0.001), at a
      drug concentration of 1-25 ng/ml for FK506 and 100-500 ng/ml for CsA. Lymphocyte
      synthesis of interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and TNF-beta
      after SEA activation was also significantly reduced by either of the drugs. In
      contrast, endotoxin-induced monokine production (TNF-alpha and IL-6) after
      lipopolysaccharide (LPS) stimulation was unaffected by FK506 or CsA even when
      added in concentrations as high as 1000 ng/ml. When the cells were stimulated by
      phorbol ester (phorbol 12-myristate 13-acetate, PMA) plus calcium ionophore
      (ionomycin), FK506 and CsA inhibited, in a dose-dependent manner, the production
      of IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha. The 50% inhibitory concentration
      (IC50) for FK506 or CsA on the cellular synthesis of the various cytokines varied
      between 0.6 and 1.0 ng/ml and 20 and 60 ng/ml, respectively. Further stimulation
      by addition of anti-CD28 mAb to the cultures resulted in an augmented IL-2 and
      IFN-gamma production which was resistant to both FK506 and CsA. This report
      delineates extensive similarities between the two drugs in mechanisms of
      immunosuppression by blockade of identical interleukin production. Depending on
      the mode of cell activation the two drugs inhibited not only cytokine production
      in lymphocytes but also antigen-induced monokine (TNF-alpha) production in
      macrophages, although the optimal immunomodulatory effect of FK506 was achieved
      at a concentration approximately 50-fold lower than that of CsA.

PMID- 1371492
TI  - Anti-platelet autoantibodies from ITP patients recognize an epitope in GPIIb/IIIa
      deduced by complementary hydropathy.
AB  - Idiopathic thrombocytopenic purpura (ITP) is a frequent platelet disorder due to
      the presence of anti-platelet autoantibodies. Recently a fibronectin/fibrinogen
      receptor in platelets, integrin GPIIb/IIIa, has been implicated as the antigen in
      chronic ITP. To examine the epitopes involved in the autoimmune response against
      GPIIb/IIIa we have used concepts from the complementary hydropathy principle. We
      used the peptide Trp-Thr-Val-Pro-Thr-Ala, WTVPTA (deduced from the complementary
      nucleotide sequence to that which codes for the Arg-Gly-Asp, RGD, domain in
      fibronectin), to test the immunologic activity of ITP sera. Sera from 31 patients
      with clinically defined ITP were tested in ELISA for reactivity towards WTVPTA
      and affinity purified GPIIb/IIIa. Seventeen sera (57%) reacted strongly with the
      glycoprotein complex, five of which reacted with the peptide. By affinity
      chromatography of one of these sera, we were able to show that antibodies that
      bind to the peptide are within the population that binds to GPIIb/IIIa. Liquid
      phase competition experiments revealed that binding of ITP serum to WTVPTA was
      inhibited only by a hydropathically compatible peptide. Our data indicate that
      autoantibodies can bind to hydropathically generated antigenic determinants and
      thus, render these peptides clinically important as diagnostic tools.

PMID- 1371493
TI  - Phenotypic analysis of complement receptor 2+ T lymphocytes: reduced expression
      on CD4+ cells in HIV-infected persons.
AB  - While expression of complement receptor 2 (CR2) (CD21) on some CD4+ cell lines
      renders them more susceptible to infection by complement-treated human
      immunodeficiency virus (HIV), coexpression of CR2 and CD4 on peripheral blood
      lymphocytes has not, until recently, been observed. Several recent studies,
      however, have found that human T lymphocytes express low levels of CR2.
      Additionally, complement treatment of HIV before addition to these cells has been
      reported to increase virus expression in peripheral blood lymphocyte cultures.
      These findings suggest that complement-mediated enhancement of infection of human
      T cells could occur in vivo and have prompted us to examine both the phenotypic
      properties of CD4+CR2+ T cells in healthy persons and the expression of CR2 on
      CD4+ lymphocytes during HIV infection. As was previously reported, we observed
      CR2 on a proportion (10-50%) of both CD8+ and CD4+ T cells. Approximately half of
      CD4+CR2+ cells expressed the memory cell markers CD45RO and CD29, 80% expressed
      the naive marker CD45RA, while 22% expressed CD25. These values were not
      substantially different from total CD4+ cells. Stimulation of lymphocytes with
      phytohaemagglutinin (PHA), OKT3 or calcium ionophore but not with phorbol
      myristate acetate (PMA) or interleukin-2 (IL-2) decreased expression of CR2 on
      CD4 cells by half over a 3-day culture period. The per cent of CD4+ cells
      expressing CR2 was significantly decreased in patients with asymptomatic and
      symptomatic HIV infection compared to uninfected control donors (P = 0.0001). In
      contrast, the decrease in CR2 expression was not observed with CD8+ lymphocytes
      from HIV-infected persons. These results confirm that CR2 is expressed on human T
      lymphocytes and suggest that a subset of CD4+ lymphocytes is selectively affected
      in HIV-infected individuals.

PMID- 1371494
TI  - Antigen-specific and polyclonal CD4+ lamina propria T-cell lines: phenotypic and
      functional characterization.
AB  - Surface phenotype and function of lamina propria CD4+ T cells have been
      evaluated. In addition, long-term, antigen-specific and polyclonal lamina propria
      CD4+ T-cell lines have been generated and characterized. Lamina propria CD4+ T
      cells represent approximately 30% of lamina propria lymphocytes and are
      responsive to a variety of T-cell mitogens, including anti-CD3, concanavalin A,
      phytohaemagglutinin and pokeweed mitogen. In each case, however, lamina propria T
      cells are less responsive to these mitogens than spleen T cells. Freshly isolated
      lamina propria T cells produce substantial amounts of interleukin-2 (IL-2),
      interleukin-4 (IL-4), gamma interferon and to a lesser extent interleukin-5 (IL
      5). Antigen-specific lamina propria CD4+ T-cell lines were generated by orally
      immunizing animals with antigen (KLH) in conjunction with cholera toxin as an
      oral adjuvant. Polyclonal lamina propria CD4+ T-cell lines were generated from
      unimmunized animals using anti-CD3 as a polyclonal stimulus. Both antigen
      specific and polyclonal CD4+ T-cell lines were Thy-1+, alpha beta TCR+ and CD8-.
      The antigen-specific CD4+ T-cell line when stimulated by anti-CD3 and PMA
      produces predominantly IL-2, IL-4 and gamma interferon, with very little IL-5. In
      contrast, the polyclonal CD4+ T-cell line when similarly stimulated produces
      predominantly IL-4 and IL-5, with very little IL-2 and no detectable gamma
      interferon. In summary, lamina propria CD4+ T cells have been evaluated and in
      vitro conditions have been determined for successful generation of lamina propria
      CD4+ T-cell lines.

PMID- 1371495
TI  - T-helper functions in lines of mice selected for high or low antibody production
      (Selection III): modulation by anti-CD4+ monoclonal antibody.
AB  - T-helper function was evaluated in mice genetically selected for high (H) or low
      (L) antibody (Ab) responsiveness to Salmonella flagellar antigen (Ag) (Selection
      III). In this Selection as opposed to what was demonstrated in Selections I, II
      and IVA, the interline difference was not proven to be based upon the
      modification of Ag processing and presentation at macrophage level. CD4+/CD8+
      lymph node ratio is similar in HIII and LIII mice, both lines being equally
      susceptible to in vivo depletion of CD4+ T cells by GK 1-5 monoclonal antibody
      (mAb) treatment. Nevertheless, the Ab responsiveness of the two lines was
      differently modulated by GK 1-5 mAb: the inhibition of Ab responses to various Ag
      required lower mAb doses and was long lasting in LIII as compared to the
      transient effect of higher mAb doses observed in HIII. LIII mice were also
      refractory to Salmonella-induced reversion of GK 1-5 mAb inhibition. Moreover, in
      vitro specific I proliferation was constantly lower in LIII, though its IL-2
      production was unexpectedly similar to that of HIII T cells. Results of in vivo
      and in vitro experiments are thus consistent with a defective response of T
      helper cells to immunogenic challenge in LIII mice.

PMID- 1371496
TI  - Primary and secondary human in vitro T-cell responses to soluble antigens are
      mediated by subsets bearing different CD45 isoforms.
AB  - A culture system has been developed which consistently supports in vitro
      proliferative responses to conventional soluble antigens by human CD4+ T cells
      from non-immunized donors. T cells exposed to an antigen in primary cultures
      could be restimulated in vitro in an antigen-specific manner to give secondary
      responses with greater magnitudes and a more rapid onset than the initial
      reaction. To characterize further the responding T-cell population in primary
      compared with secondary reactions, T cells were depleted of CD45RA+ or CD45RO+
      cells and stimulated with recall and non-recall antigens. It was found that the
      soluble non-recall antigen keyhole limpet haemocyanin did not stimulate CD45RO+ T
      cells, yet induced strong proliferative responses from CD45RA+ T cells.
      Conversely, it was confirmed that human CD45RO+ T cells respond to the recall
      antigen-purified protein derivative from Mycobacterium tuberculosis. Cell mixing
      experiments indicated that CD45RO+ T cells are unlikely to have any suppressive
      effect on the reactivity of CD45RA+ cells to non-recall antigens. These data
      provide new support for the hypothesis that CD45RA+ represents the naive and
      CD45RO+ the memory phenotype of human CD4+ T cells.

PMID- 1371497
TI  - Pattern of lectin binding to murine T lymphocytes.
AB  - Lectins can be used to detect changes in cell-surface glycosylation. In this
      paper we examine the lectin-binding characteristics of murine T cells as measured
      by flow cytometry. A large panel of labelled lectins was used to stain naive,
      activated and resting murine T cells. Some lectins did not detectably bind any T
      cells, some bound to all T cells and some bound to only a subset of splenic T
      cells. Three lectins which preferentially bind to previously activated T cells
      were identified: Bandeiraea simplicifolia BS-I, Bauhinia purpurea and
      Lycopersicon esculentum. In addition, two lectins were found to bind
      preferentially to activated T cells: Glycine max and Triticum vulgaris. Finally,
      no differences were found in the ability of a large panel of lectins to bind to
      Th1 and Th2 clones. Lectin binding may be a powerful tool for distinguishing
      naive, activated and memory T cells.

PMID- 1371498
TI  - A Tcra congenic mouse: V alpha epitope expression is influenced by both Tcra
      haplotypes and background genes.
AB  - A T-cell receptor alpha chain locus (Tcra) congenic mouse is described. The Tcraa
      haplotype of BALB/c (donor strain) was bred on to B10.D2 (background strain,
      Tcrab haplotype) by using a Bgl I Tcra-C restriction fragment length
      polymorphism. Tcraa/b heterozygous offspring from the eleventh backcross
      generation were brother-sister mated to obtain Tcra-Ca homozygous animals. The
      resulting congenic line, B10.D2.C-Tcraa/Bo carries a recombination between the
      Tcra and the hr loci; thus, the transferred differential segment is the
      centromeric 18-27 cM of the BALB/c chromosome 14. Analysis with a multitude of
      Tcra-V and Tcrd-V probes demonstrates that the complete Tcraa haplotype is
      contained within this differential segment. Lymph node T cells of BALB/c (Tcraa)
      B10.D2 (Tcrab) and B10.D2.C-Tcraa were stained with anti-V alpha 8 (KT50, KT65),
      anti-V alpha 3.2 (RR3-16) and anti-V alpha 11.1 and 2 (RR8-1) monoclonal
      antibodies. We find that the frequencies of V alpha epitope expression are highly
      Tcra haplotype-dependent even though an influence of background genes is also
      observed. Thus, Tcra-V germline differences may possibly influence the T cell
      repertoire, in addition to the already well known positive and negative thymic
      selections. Tcra haplotype does not influence the frequencies of V beta
      utilization. However, BALB/c mice have fewer V beta 11+ T cells than B10.D2 and
      B10.D2-Tcraa, therefore, the BALB/c genome must harbor a V beta 11 deleting
      gene(s) in addition to those described so far.

PMID- 1371499
TI  - Chromosome 14 in B10.A(18R) mice is recombinant and includes Tcra-Va alleles.
AB  - Analysis of mouse Tcr genes has previously defined at least five different Tcra-V
      haplotypes among inbred strains of mice. For mice of the Tcra-Vb haplotype,
      including C57BL/10 (B10), T-cell expression of the Tcra-V11 gene subfamily can be
      detected with a monoclonal antibody, 1.F2. In the course of further
      characterizing the specificity of 1.F2, we found that it fails to recognize Tcra
      V11-expressing T-cell hybrids derived from the B10 congenic strain,
      B10.A(18R)/SgIcr. Moreover, staining analysis indicated that the Va11 epitope
      recognized by 1.F2 is not expressed by peripheral T cells from several different
      B10.A(18R) colonies with the exception of that at the Research Institute of
      Scripps Clinic. Nucleotide sequences were determined for cDNA representing
      rearranged Tcra-V11 genes from two independent, B10.A(18R)/SgIcr derived T-cell
      hybrids. The two Tcra-V11 gene segments were identical and the predicted amino
      acid sequence differed by at least five residues from Tcra-V11 sequences
      previously obtained from B10.A mice. Southern blot analysis of restriction
      fragment length polymorphisms (RFLP) associated with Tcra-V11, as well as Tcra
      V1, subfamily genes revealed that the B10.A(18R) mouse has inherited Tcra-Va
      alleles rather than the expected Tcra-Vb alleles from the B10 strain. RFLP
      analysis of the Rib-1 locus, located in close proximity to the Tcra locus on
      chromosome 14, showed that B10.A(18R) carries the Rib-1b allele from B10. These
      results indicate that the B10.A(18R) mouse has inherited a recombinant chromosome
      14 with a recombination event having occurred between the Rib-1 locus and the
      Tcra-V gene subfamilies examined. Inheritance of Tcra-Va alleles in B10.A(18R)
      probably originated from strain 129/J which breeding records show was used in the
      first cross with B10.A in the production of B10.A(18R) and which we found
      exhibits Tcra-V11a RFLPs.

PMID- 1371501
TI  - Tissue-specific regulation of inflammation.
AB  - Proteins of the complement system are important effectors and modulators of
      inflammation. The complement cascade is triggered by microbes, tissue debris, and
      specific antibodies. Serum complement proteins are derived primarily from liver,
      but extrahepatic complement synthesis is important in homeostasis and in local
      host defenses. Tissue-specific regulation of expression of complement genes is
      governed by mechanisms similar to those that regulate other "acute phase
      reactants." That is, tissue injury or infection elicit changes in expression of
      these acute phase proteins, which, although variable in kinetics, magnitude, and
      direction, are a consequence of an elaborate system of cell-to-cell
      communication. This communication is mediated via a complex network of cytokines,
      including the interferons, interleukins, several growth factors, and sex
      hormones. The cell biological and molecular biological details of these
      mechanisms are now under active investigation. An understanding in molecular
      terms of the balance between proinflammatory and counterregulatory forces on
      complement gene expression should provide new insight into the functions of
      complement and the design of novel therapies for disorders of inflammation.

PMID- 1371500
TI  - Distribution of individual components of basement membrane in human colon polyps
      and adenocarcinomas as revealed by monoclonal antibodies.
AB  - Double-label immunofluorescence was used to monitor basement-membrane composition
      and integrity in 22 human colon polyps, 36 adenocarcinomas and 2 metastases.
      Cryostat sections were stained with polyclonal anti-laminin anti-serum combined
      with monoclonal antibodies (MAbs) to all major basement-membrane components
      (laminin, entactin/nidogen, collagen type IV and large heparan sulfate
      proteoglycan), as well as to keratin 8. In all adenocarcinomas, including
      mucinous, basement membranes were altered more at the invasive front than in the
      parenchyma. The degree of this alteration was inversely correlated with the level
      of tumor differentiation. An uncoordinated loss of basement membrane components
      (dissociation of markers), previously described by us in rat colon
      adenocarcinomas, was also found in human tumors. In the great majority of
      adenocarcinomas a pronounced stromal reaction was seen. It was manifested by the
      presence of fibrillar deposits of basement-membrane components, mainly of
      collagen type IV and/or heparan sulfate proteoglycan. This reaction was never
      observed in polyps and may be derived from myofibroblasts reported to accumulate
      in colon cancer stroma. The combined use of antibodies to basement-membrane
      components and to a specific keratin may constitute an adequate
      immunohistochemical test for the presence of invasion, and may be useful in the
      histologic analysis of polyps, especially in dubious cases.

PMID- 1371502
TI  - Increased negativity of interstitial fluid pressure in rat trachea in dextran
      anaphylaxis.
AB  - This study shows that, in rat trachea, dextran anaphylaxis is associated with
      increased negativity of interstitial fluid pressure (Pif) as measured with
      sharpened glass capillaries (tip diameter 3-7 microns) connected to a servo
      controlled counterpressure system. Experiments were carried out in pentobarbital
      anesthetized Wistar-Moller rats. Pif in the control situation was -2.5 +/- 0.38
      (SD) mmHg. The mean pressure in animals killed 2 min after initiation of the
      anaphylactic reaction by injection of 1 ml of 10% Dextran 70 in 0.9% NaCl was 
      10.3 +/- 2.6 mmHg. In another experimental series, interstitial fluid volume was
      measured after dextran administration but without inducing circulatory arrest.
      Interstitial fluid volume increased from 0.94 +/- 0.16 to 1.56 +/- 0.42 ml/g dry
      wt after 10 min to 1.57 +/- 0.30 and 1.10 +/- 0.27 ml/g dry wt after 30 and 60
      min, respectively. The increased negativity in Pif in tracheal mucosa in the
      early phase of dextran anaphylaxis will markedly increase the transcapillary net
      filtration pressure in the initial phase of edema development.

PMID- 1371503
TI  - Growth of human renal cortical tissue on collagen gel.
AB  - A model system for 3-dimensional "native-state" culture of tissues on collagen
      gels (Proc. Natl. Acad. Sci. USA 86:2013-2017; 1989) has been applied in this
      study to histologically normal human renal cortical tissue from 11 patients
      undergoing nephrectomy for renal cell carcinoma elsewhere in the kidney.
      Microbial contamination occurred in 12/90 cultures, the rest (78) were studied by
      visual inspection, histology, immunohistochemical analysis for pankeratin
      (epithelial cell origin), vimentin (mesenchymal cell origin), and p-glycoprotein
      (associated with proximal tubules), transmission electron microscopy (EM),
      incorporation of tritiated thymidine (3HTdR). In the first 10 days, explants
      showed 3HTdR-labeled cells in tubule structures. The surrounding gel was invaded
      by cells forming tubule structures, sometimes with basement membrane. Some of
      these cells showed labeling by 3HTdR and immunostaining positive for pankeratin
      and p-glycoprotein. EM showed well-polarized epithelial cells in tubule
      structures with tight junctions, interdigitating lateral processes, and
      microvilli characteristic of proximal and distal convoluted tubules. 3HTdR
      labeled cells in tubule structures were observed even 2 mo. after Passage 1, 6
      mo. after the initial explantation. Tubule growth was most active and fibroblast
      proliferation was negligible from 2 to 4 wk postexplantation. The proliferation
      of tubulelike cells and formation of tubulelike structures in this system
      represents an opportunity to study human renal cortical tissue in vitro, under
      conditions more closely resembling in vivo circumstances than are present in
      other in vitro systems suitable for long-term study. This model has potential use
      for in vitro toxicology studies and studies of renal physiology.

PMID- 1371504
TI  - SK HEP-1: a human cell line of endothelial origin.
AB  - SK-HEP-1 is an immortal, human cell line derived from the ascitic fluid of a
      patient with adenocarcinoma of the liver. We have determined that these cells are
      of endothelial origin. Despite the location of the tumor from which SK HEP-1 was
      derived, the cell line does not have properties of hepatocytes. Northern blot
      analysis of total cellular RNA shows no messenger RNA for the hepatic-specific
      proteins albumin, alpha-fibrinogen, or gamma-fibrinogen. Endothelial
      characteristics are seen by transmission electron microscopy. These features
      include numerous pinocytotic vesicles, electron dense granules consistent with
      Weibel-Palade bodies, and abundant intermediate filaments, identified
      immunocytochemically as vimentin. Cultures grown on plastic dishes grow in
      bundles of polygonal to spindle-shaped cells. Proteins characteristic for
      endothelial cells are identified by immunocytochemistry. Addition of basement
      membrane material (Matrigel) or type I collagen to the cultures induces these
      cells to organize into a tubular network.

PMID- 1371505
TI  - Regulation of c-fos and ornithine decarboxylase mRNA levels by estrogen and 5
      azacytidine.

PMID- 1371506
TI  - Growth of sebaceous cells in monolayer culture.
AB  - Rat preputial cells were grown in an epithelial cell primary monolayer culture
      system identical to that used for culturing epidermal cells, which were studied
      for comparison. Despite similar appearance when observed by phase contrast
      microscopy, other features identified the preputial cells as a unique epithelial
      cell population. Preputial cells grew as a relatively small number of large
      colonies, formed domes before confluence, and expressed a specific acinar
      keratin, K4, which had previously been found in human sebaceous glands. In
      addition, preputial cells formed fewer cornified envelopes than epidermal cells,
      too few to discern the reduction of envelope formation by retinoic acid treatment
      in vitro which was found in epidermal cells. Rat preputial cells in monolayer
      culture, therefore, are a promising model for studying the effects of hormones on
      sebaceous cell growth and differentiation.

PMID- 1371507
TI  - Isoleucyl-tRNA synthetase from the ciliated protozoan Tetrahymena thermophila.
      DNA sequence, gene regulation, and leucine zipper motifs.
AB  - We have determined the nucleotide sequence of a protozoan aminoacyl-tRNA
      synthetase. The isoleucyl-tRNA synthetase (ileRS) gene [ilsA; formerly cupC,
      Martindale, D. W., Martindale, H. M., and Bruns, P. J. (1986) Nucleic Acids Res.
      14, 1341-1354] from the ciliate Tetrahymena thermophila was sequenced and found
      to have eight introns, four transcription start sites, and a putative polypeptide
      of 1081 amino acids. A polypeptide 20 amino acids longer could be made if a
      transcribed in-frame ATG close to the start sites and with suboptimal sequence
      context is used. This gene was identified through hybridization and amino acid
      sequence similarity to the previously cloned and sequenced ileRS (cytoplasmic)
      gene from Saccharomyces cerevisiae [Englisch, U., Englisch, S., Markmeyer, P.,
      Schischkoff, J., Sternbach, H., Kratzin, H., and Cramer, F. (1987) Biol. Chem.
      Hoppe-Seyler 368, 971-979; Martindale, D. W., Gu, Z. M., and Csank, C. (1989)
      Curr. Genet. 15, 99-106] with which it shares 47% of its amino acids. We also
      compared it to ileRS genes from E. coli and an archaebacterium. Two leucine
      zippers motifs were identified in the carboxyl-terminal domain of the
      polypeptide; one of these motifs is in the same area as the zinc finger motif
      found in the E. coli enzyme. The transcription pattern of the ilsA gene was
      monitored under various culture conditions and parallels changes in protein
      synthesis.

PMID- 1371508
TI  - Gene expression during 3T3-L1 adipocyte differentiation. Characterization of
      initial responses to the inducing agents and changes during commitment to
      differentiation.
AB  - The mouse 3T3-L1 fibroblastic cell line rapidly differentiates to an adipocyte
      phenotype when post-confluent cells are treated for 48 h in fetal calf serum
      containing medium supplemented with 1 microM dexamethasone (D), 0.5 mM
      methylisobutylxanthine (M) and 10 micrograms/ml insulin (I). D and I act
      synergistically to commit the cells to differentiate 24-48 h after initiating
      treatment, and this is blocked by the phorbol ester, 12-O-tetradecanoylphorbol-13
      acetate. In order to identify cellular proteins involved in the differentiation
      process we analyzed differentiating 3T3-L1 cells using two-dimensional
      electrophoresis on large format gels. We observed changes in over 300 proteins
      during differentiation (over 100 within 5 h of initiating differentiation) and
      many of these are also changed at the level of mRNA (by analysis of in vitro
      translation products). About 75% of the initial changes were maximally induced by
      treatment with a combination of M and I, while no more than 10 proteins and their
      corresponding mRNAs were maximally induced by D within 3.5 h. Another 10 proteins
      were synergistically regulated by the combination of all three agents (DMI)
      within 3.5 h. Additional species were induced at later times. Five of these were
      synergistically induced by treatments that lead to differentiation, were first
      expressed at elevated levels during commitment and remained elevated in fully
      differentiated adipocytes. One or more of these proteins could well have a
      functional role in the commitment to and/or expression of the adipocyte
      differentiation program.

PMID- 1371509
TI  - Biochemical and molecular genetic analyses on placental aromatase (P-450AROM)
      deficiency.
AB  - Biochemical and molecular genetic studies were made on a case of placental
      aromatase (P-450AROM) deficiency. Of the enzymes participating in the electron
      transport system of placental microsomes, only aromatase activity was decreased
      specifically in the patient, being less than 0.3% of the normal activity.
      Northern and Western blotting analyses showed that the transcription of the
      aromatase gene and the translation of its mRNA proceeded normally in the placenta
      of this patient. However, aromatase cDNA isolated from a placental cDNA library
      of the patient was found to have an insert of 87 base pairs, encoding 29 amino
      acids in frame with no termination codon. The insert was located at the splicing
      point between exon 6 and intron 6 of the normal aromatase gene, and the extra DNA
      fragment was the first part of intron 6, except that its initial GT was altered
      to GC. These findings indicated that in this patient with aromatase deficiency,
      splicing between exon 6 and intron 6 did not occur at the normal position because
      of a point mutation in its consensus sequence and was forwarded to GT in the next
      cryptic consensus sequence 87 base pairs downstream according to the canonical
      GT/AG rule, resulting in translation of an abnormal protein molecule with 29
      extra amino acids. During the transient expression in COS-7 cells, the aromatase
      cDNA of the patient was found to produce a protein with a trace of activity. This
      is the first report of a genetic defect for aromatase deficiency.

PMID- 1371511
TI  - Expression, synthesis, and phosphorylation of HSP28 family during development and
      decay of thermotolerance in CHO plateau-phase cells.
AB  - We investigated a correlation between development of thermotolerance and
      expression, synthesis, or phosphorylation of HSP28 family in CHO plateau phase
      cells. After heating at 45.5 degrees C for 10 min, thermotolerance developed
      rapidly and reached its maximum 12-18 hr after heat shock. This acquired thermal
      resistance was maintained for 72 hr and then gradually decayed. In parallel, the
      levels of three 28 kDa heat shock proteins, HSP28a along with its two
      phosphorylated isoforms (HSP28b,c), increased and reached their maximum 24-48 hr
      after heat shock. The levels of these polypeptides, except HSP28c, remained
      elevated for 72 hr and then decreased. The level of HSP28 mRNA increased rapidly
      and reached its maximum 12 hr after heat shock. However, unlike thermotolerance
      and the levels of HSP28 family proteins, the level of HSP28 mRNA decreased
      rapidly within 72 hr. These results demonstrate a correlation between the amount
      of intracellular HSP28 family proteins and development and decay of
      thermotolerance.

PMID- 1371512
TI  - Alpha-fetoprotein-mediated uptake of fatty acids by human T lymphocytes.
AB  - The binding to resting and activated T lymphocytes of two radiolabelled fatty
      acids (oleic and arachidonic) was studied in the presence or in the absence of
      alpha-fetoprotein (AFP) as carrier protein. Fatty acid binding by resting and
      activated T lymphocytes was determined at 4 degrees C as a function of the
      concentration of fatty acid and AFP. Under the conditions employed, the following
      observations were made: (1) in the presence of AFP, fatty acids (oleic and
      arachidonic acid) are bound to cells by a two-component pathway; one is a
      saturable process, evidenced when the fatty acid to AFP (FA/AFP) molar ratio was
      fixed at 1 and the concentration of the fatty acid and the protein varied from
      0.1 to 3.2 microM, and the second is a nonsaturable function of FA/AFP molar
      ratio and was linearly related to the unbound fatty acid concentration in the
      medium over the entire range studied; (2) in the absence of AFP, the nonsaturable
      process appears to be the only component of fatty acid binding; 3) at all tested
      concentrations of free (unbound) fatty acid in the medium, net fatty acid binding
      by either resting or activated T cells was considerably greater in the presence
      than in the absence of AFP; (4) in the presence of AFP, fatty acid binding was
      much higher in activated T cells than in resting T cells, whereas in the absence
      of AFP, nonsignificant differences were observed between activated and resting T
      cells; and (5) the time course of fatty acid and AFP binding at 4 degrees C
      revealed that, at equilibrium, the number of fatty acid molecules bound to the
      cell was much greater than that of AFP suggesting an accelerated dissociation of
      the fatty acid upon interaction of the AFP-fatty acid complex with putative cell
      receptors. It is concluded to the existence of an AFP/AFP-receptor pathway that
      facilitates the binding of fatty acids to T lymphocytes, particularly upon their
      blast transformation. This pathway may fulfill the increased requirement for
      fatty acids characteristic of proliferating cells and may serve to regulate the
      endocytosis of fatty acids with modulatory effects on lymphocyte function and to
      protect cells from their cytotoxic potential when internalized in excess.

PMID- 1371510
TI  - Biochemical properties of chimeric skeletal and smooth muscle myosin light chain
      kinases.
AB  - The molecular and biochemical properties of myosin light chain kinases from
      chicken skeletal and smooth muscle were investigated by recombinant DNA
      techniques. Deletion of the amino-terminal region of either the smooth or
      skeletal muscle myosin light chain kinase resulted in a decrease in Vmax with no
      significant change in Km values for light chain substrates. Skeletal/smooth
      muscle chimeric kinases were inactive when a 65-residue region amino-terminal of
      the catalytic core was exchanged between the two forms. Changing alanine 494 to
      glutamic acid within this region in the chicken skeletal muscle myosin light
      chain kinase increased the Km values for light chains 10-fold. These results are
      consistent with the hypothesis that the region amino-terminal of the catalytic
      core in myosin light chain kinases is involved in light chain recognition. A
      skeletal muscle kinase which contained the smooth muscle calmodulin binding
      domain remained regulated by Ca2+/calmodulin. Thus, the calmodulin binding
      domains of smooth and skeletal muscle myosin light chain kinases share structural
      elements necessary for regulation.

PMID- 1371513
TI  - Vasoactive intestinal peptide and forskolin regulate proliferation of the HT29
      human colon adenocarcinoma cell line.
AB  - Although several lines of evidence implicate cAMP in the regulation of intestinal
      cell proliferation, the precise role of this second messenger in the control of
      the human colon cancer cell cycle is still unclear. In order to investigate the
      role of cAMP in HT29 cell proliferation, we have tested the effect of vasoactive
      intestinal peptide (VIP) and forskolin on DNA synthesis and cell number, focusing
      on the time-dependent efficacy of the treatment. The cells were arrested in G0/G1
      phase by incubation for 24 h in serum-free medium and proliferation was re
      initiated by addition of either 85 nM insulin or 0.5% fetal calf serum. In the
      presence of fetal calf serum, G1/S transition was found to occur earlier than
      with insulin. Exposure of the HT29 cells to 10(-5) M forskolin in the early
      stages of growth induction (within 12 h from FCS addition or within 14 h from
      insulin treatment) resulted in a significant inhibition of DNA synthesis and a
      delayed entry in the S phase. By contrast, VIP (10(-7) M) was inhibitory only
      when added within a narrow window (10 to 12 h or 12 to 14 h following FCS or
      insulin addition, respectively). The difference in efficiency of forskolin and
      VIP to inhibit cell proliferation may be correlated with their own potency to
      promote long-lasting cAMP accumulation. The combination of VIP plus forskolin had
      synergistic effects on both cAMP accumulation and cell-growth inhibition. Taken
      together, our data indicate that cAMP may act at a step in the late G1 or G1/S
      transition.

PMID- 1371514
TI  - Common senescent cell-specific antibody epitopes on fibronectin in species and
      cells of varied origin.
AB  - The phenomenon of in vitro cellular senescence has been demonstrated in cultured
      cells derived from humans and various other species. We have previously shown
      that monoclonal antibodies SEN-1, SEN-2, and SEN-3 react to epitopes on
      fibronectin that are exposed when human diploid fibroblasts become senescent. We
      here present results demonstrating that exposure of these epitopes is specific to
      senescence for a variety of human cells: epidermal keratinocytes, mammary
      epithelial cells, as well as fibroblasts. Fibronectin from 11 additional species
      was also analyzed by Western immunoblot for ability to bind the SEN antibodies.
      SEN-1 bound only human and gorilla fibronectin, whereas SEN-2 and SEN-3 bound
      fibronectin from those two species as well as the horse, cow, sheep, goat, dog,
      and chick. None of the antibodies reacted with fibronectin from the rabbit, rat,
      or mouse. These data indicated a correlation between the ability of the SEN
      antibodies to bind fibronectin from a particular species and the ability of cells
      from that species to exhibit a stable senescent phenotype in vitro. Therefore,
      exposure of this region of fibronectin may be important in the establishment and
      maintenance of cellular senescence. In addition, the ability of the SEN
      antibodies to react with fibronectin from a variety of senescent cells emphasizes
      their usefulness as markers for cellular senescence.

PMID- 1371515
TI  - Characterization of a novel Rochalimaea species, R. henselae sp. nov., isolated
      from blood of a febrile, human immunodeficiency virus-positive patient.
AB  - Isolation of a Rochalimaea-like organism from a febrile patient infected with
      human immunodeficiency virus was confirmed. Analysis of 16S rRNA gene sequences,
      together with polymerase chain reaction and restriction endonuclease length
      polymorphism analysis of a portion of the citrate synthase gene, demonstrated
      that the agent is closely related to members of the genus Rochalimaea and that
      the isolate is genotypically identical to the presumptive etiologic agent of
      bacillary angiomatosis. However, the same genotypic analyses readily
      differentiated the new isolate from isolates of other recognized Rochalimaea
      species as well as other genera of bacteria previously suggested as putative
      etiologic agents of bacillary angiomatosis and related syndromes. We propose that
      the novel species be referred to as Rochalimaea henselae sp. now.

PMID- 1371518
TI  - Clinical and laboratory analyses of cytospin-prepared Gram stains for recovery
      and diagnosis of bacteria from sterile body fluids.
AB  - The smear of a clinical specimen provides essential laboratory information that
      is used to make therapeutic decisions. For this study, smears were made by
      centrifugation in a Beckman Microfuge 11 (Beckman Instruments, Palo Alto, Calif.)
      and in parallel by using a Cytospin 2 apparatus (Shandon Inc., Pittsburgh, Pa.).
      Of 350 consecutive body fluid specimens examined, 50 (14.0%) grew bacteria. Both
      methods were culture and smear positive for 24 (6.9%) specimens; 18 (5.1%)
      specimens were cytocentrifuge smear positive, culture positive, and high-speed
      centrifugation (HSC) negative; 3 (0.8%) were culture negative and positive by
      both smear methods; and 1 (0.2%) was HSC smear positive, culture positive, and
      cytocentrifuge negative. Seven (2.0%) specimens were culture positive and
      negative by both smear methods. Clinically, cytocentrifuge preparations showed
      greater sensitivity for culture-positive specimens and a closer correlation with
      the CFU per milliliter than HSC did, resulting in a greater ability to treat
      patients with specific therapies. In addition, analysts needed to examine only a
      6-mm-diameter area on the slide, cells and microbes were somewhat larger and more
      regular in appearance, and smears stained more uniformly. Because of the
      increased clinical and laboratory utility of the cytocentrifuge, its use is
      recommended in clinical microbiology laboratories for all sterile body fluid
      specimens.

PMID- 1371517
TI  - Epidemiologic typing of Staphylococcus aureus by DNA restriction fragment length
      polymorphisms of rRNA genes: elucidation of the clonal nature of a group of
      bacteriophage-nontypeable, ciprofloxacin-resistant, methicillin-susceptible S.
      aureus isolates.
AB  - Analysis of DNA restriction fragment length polymorphisms of rRNA genes
      (ribotyping) was employed to assist in the epidemiologic investigation of the
      emergence and spread of ciprofloxacin-resistant Staphylococcus aureus at the
      Atlanta VA Medical Center because many isolates of interest were nontypeable by
      phages and harbored few plasmids useful as strain markers. Chromosomal DNAs of
      selected S. aureus isolates were digested initially with 20 different restriction
      enzymes. EcoRI appeared to give the best discrimination of hybridization banding
      patterns (ribotypes) and was used with all study isolates. Overall, 15 different
      ribotypes were seen among the 50 S. aureus isolates studied (7 ribotypes among 13
      methicillin-susceptible S. aureus [MSSA] isolates and 9 ribotypes among 37
      methicillin-resistant S. aureus [MRSA] isolates). Seven of eight ciprofloxacin
      resistant MSSA (CR-MSSA) patient isolates had identical antibiograms, were
      nontypeable by phages, and had a single 22-MDa plasmid. Six of these seven CR
      MSSA isolates had an identical ribotype pattern. Ribotyping distinguished this CR
      MSSA strain or clone from MRSA and other MSSA isolates, including nontypeable
      isolates that contained a 22-MDa plasmid. Five ciprofloxacin-susceptible MSSA
      isolates studied had five ribotypes; one pattern was identical to the CR-MSSA
      clone. Twenty-three CR-MRSA isolates recovered from the Atlanta VA Medical Center
      had four different ribotypes. Ribotyping proved to be a useful molecular
      epidemiologic tool in the study of S. aureus because it differentiated isolates
      which were indistinguishable by more traditional methods. In addition, this
      technique demonstrated that at our institution, ciprofloxacin resistance emerged
      in multiple strains of MRSA, as opposed to primarily a single strain or clone of
      MSSA.

PMID- 1371516
TI  - Monoclonal antibodies and chemiluminescence immunoassay for detection of the
      surface protein of human T-cell lymphotropic virus.
AB  - Monoclonal antibodies (MAbs) raised against human T-cell lymphotropic virus type
      I (HTLV-I) recognized five distinct antigenic domains of viral env gene-encoded
      proteins. By using recombinant env proteins and synthetic peptides as mapping
      antigens, it was determined that the most immunogenic region represented a
      central portion of the retroviral surface protein (domain 2; amino acids 165 to
      191). However, only a single MAb was able to react strongly with native viral
      proteins. This antibody (clone 6C2) was directed to an epitope within domain 4
      (amino acids 210 to 306) of the retroviral env gene and reacted with envelope
      proteins in both HTLV-I and HTLV-II, as determined by immunoprecipitation, solid
      phase binding, and immunoblotting. No reactivity against envelope components of
      other human retroviruses, including human immunodeficiency virus types 1 and 2,
      was present. Flow cytometry data demonstrated that MAb 6C2 reacted with cell
      lines chronically infected with HTLV-I or HTLV-II and also with surface antigens
      expressed on fresh adult T-cell leukemia cells, following up-regulation with
      interleukin-2. By a chemiluminescence immunoassay procedure, picogram amounts of
      viral surface protein could be detected in the unconcentrated supernatants of
      HTLV-infected cell lines and in diagnostic cultures. Levels of env and gag
      proteins released by cells into culture supernatants were not directly related to
      percent expression of cell surface viral-coat proteins. Further, the molar ratio
      of p19 to gp46 in conditioned media varied from strain to strain, possibly
      reflecting differences in viral assembly or packaging mechanisms. MAb 6C2 will be
      of value in characterizing the biochemical and immunological behavior of
      retroviral env gene proteins and in studying the interaction of HTLV-I and HTLV
      II with their receptors.

PMID- 1371519
TI  - Pneumocystis carinii and specific fungi have a common epitope, identified by a
      monoclonal antibody.
AB  - Because Pneumocystis carinii may be related to fungi, we evaluated the
      reactivities of monoclonal antibodies raised against P. carinii with a variety of
      fungi. Fifty-two fungi and six protozoa were evaluated by immunofluorescence. One
      of three monoclonal antibodies (MAbs) tested (MAb 7D7) reacted with 15 fungi but
      no protozoa. Saccharomyces cerevisiae showed the strongest reactivity by
      immunofluorescence. The reactive antigen was characterized for four fungi by the
      immunoblot technique. In all cases the antigen that was reactive with MAb 7D7 was
      larger than the P. carinii antigens that reacted with 7D7. In further studies
      with P. carinii, Aspergillus species, and S. cerevisiae, we found that MAb 7D7
      reacted with a carbohydrate component in all organisms. The presence of an
      epitope that is common to P. carinii and a number of fungi further supports the
      fungal nature of P. carinii.

PMID- 1371521
TI  - Local immune responses to the Campylobacter flagellin in acute Campylobacter
      gastrointestinal infection.
AB  - Intestinal immunoglobulin A (IgA) anti-campylobacter flagellin antibodies were
      measured by an enzyme-linked immunosorbent assay in patients with and without
      campylobacter infections. The level of fecal IgA antiflagellin antibodies was
      significantly higher in patients than in controls, but only 12 of 29 patients
      (41.4%) with a campylobacter infection had detectable IgA antibodies against
      flagellin (optical density, greater than or equal to 0.100). Further testing of
      fecal IgA antibodies from 10 patients with homologous and heterologous purified
      flagellins showed strain specificity in 1 patient. Cross-reactivity of fecal IgA
      antibodies with heterologous flagellins did not correlate with the Lior serotype
      of the isolate.

PMID- 1371520
TI  - Evidence for two serotype G3 subtypes among equine rotaviruses.
AB  - Ten cultivable equine rotavirus isolates, two of North American, six of British,
      and two of Irish origin, were compared with standard rotavirus strains and with
      each other by cross neutralization, neutralization with a panel of monoclonal
      antibodies (MAbs), hybridization to a simian rotavirus (SA-11) VP7 gene probe,
      and reaction with rotavirus subgrouping and serotyping MAbs in enzyme-linked
      immunosorbent assays. Six isolates, two of which had previously been serotyped as
      G3 by other workers, were found to be serotype G3; one was confirmed to be G5,
      and three were not related to serotypes G1 to G10. The serotype G3 strains were
      divisible into two subtypes, G3A and G3B, on the basis of cross neutralization.
      This division was also apparent in reactions with neutralizing VP7-specific MAbs
      and in the liquid hybridization assay. Two of the isolates were not bound by
      either subgroup MAb, six were bound by both subgroup I and II MAbs, and two were
      bound by only the subgroup I MAb. The assays used in this characterization
      provide a range of epidemiological information for use in future field
      investigations.

PMID- 1371522
TI  - Intracellular events involved in CD5-induced human T cell activation and
      proliferation.
AB  - In this report we describe a novel pathway of human T cell activation and
      proliferation involving the CD5 surface Ag. The CD5-specific Cris1 mAb induces by
      itself monocyte-dependent proliferation of PBMC. Among a panel of CD5-specific
      mAb (Leu1, OKT1, LO-CD5a, F101-1C5, and F145GF3), only the F145GF3 mAb shared
      this property with Cris1. The analysis of the biochemical pathway involved in
      this activation showed the lack of detectable hydrolysis of inositol phosphates
      or early increments in the intracellular cytosolic calcium concentration, after
      triggering cells with the mitogenic CD5 mAb. However, stimulation with CD5
      induces activation of protein kinase C, as measured by phosphorylation of a
      specific peptide substrate (peptide GS), which can be inhibited by a
      pseudosubstrate peptide inhibitor. Stimulation with CD5 mAb induces also tyrosine
      kinase activity, with a substrate pattern that differs from that induced after
      triggering lymphocytes through the TCR-CD3 complex. On the other hand the IL-2/IL
      2R pathway seems involved in the CD5-mediated proliferation of PBMC because anti
      IL-2R-specific mAb inhibits CD5-induced proliferation, and stimulation with
      mitogenic CD5 mAb induces production of IL-2 and expression of IL-2R alpha and
      beta chains. Therefore, the triggering of the CD5 Ag can induce IL-2- and
      monocyte-dependent human T cell proliferation by a biochemical pathway that
      differs, at least in the first stages, from the one that mediates TCR-CD3 complex
      induced T cell activation.

PMID- 1371523
TI  - Gene transfer demonstrates that the V gamma 1.1C gamma 4V delta 6C delta T cell
      receptor is essential for autoreactivity.
AB  - Murine T cell lines and hybridomas derived from the epidermis that express the V
      gamma 1.1C gamma 4V delta 6C delta TCR and may, therefore, recognize an
      autoantigen, secrete cytokines spontaneously in culture. In addition, activation
      of these cells requires engagement of the vitronectin receptor (VNR) by
      extracellular matrix proteins. To further evaluate the role of the TCR, the VNR,
      and the putative autoantigen in the activation of this T cell subset, we cloned
      complete cDNA encoding the V gamma 1.1C gamma 4 and V delta 6C delta TCR and
      transfected the cDNA constructs into a TCR- murine hybridoma and into a TCR-
      variant of the human Jurkat line. The murine transfectant spontaneously produced
      IL-2 in culture and IL-2 production could be inhibited by anti-CD3,
      anticlonotypic mAb to the transfected TCR, and anti-VNR mAb, as well as by RGDS.
      These results demonstrate that transfection of the gamma delta TCR confers to
      recipient T cells the phenotype of constitutive activation, as well as dependence
      on engagement of the VNR as an accessory molecule. In contrast, the Jurkat gamma
      delta transfectant failed to produce cytokines spontaneously, although the
      transfected TCR was capable of signal transduction after stimulation by anti-TCR
      mAb. Surprisingly, neither the murine transfectant nor the human transfectant
      could be induced to respond to autoantigen bearing cells in coculture assays. One
      interpretation of these results is that coexpression on the surface of the same
      cell of the V gamma 1.1 V delta 6 TCR, the VNR, and a putative autoantigen are
      necessary for T cell activation in this system.

PMID- 1371524
TI  - Monoclonal antibodies directed to different epitopes in the CD3-TCR complex
      induce different states of competence in resting human T cells.
AB  - After the initial stages of activation, T cells are not able to proliferate on
      their own but become competent to proliferate in response to exogenously added
      lymphokines. In the present study we compared the capacity of mAb directed to CD3
      (OKT3, Leu4, UCHT1) or to common epitopes on the alpha/beta T-cell receptor (BMA
      031, BMA 032) to induce competence in purified resting T cells. Stimulation with
      either soluble anti-CD3 or anti-alpha/beta TCR mAb rendered cells competent to
      progress to DNA synthesis in response to exogenous IL-2. In contrast, only
      soluble BMA 031 and BMA 032 were able to induce responsiveness to IL-4; anti-CD3
      mAb had either to be immobilized or used in combination with anti-CD28 mAb to
      induce responsiveness to IL-4. Further, BMA 031-induced IL-4 responsiveness was
      selectively found in the CD45RA+ T cell subset. Analysis of early activation
      events revealed that the capacity of soluble BMA 031 and BMA 032 to induce
      responsiveness to IL-4 did not correlate with the ability of these mAb to
      increase the level of cytosolic Ca2+ or to induce detectable tyrosine
      phosphorylation. On the other hand, soluble Leu4 (anti-CD3) triggered an increase
      in both intracellular Ca2+ and tyrosine phosphorylation but was unable to induce
      IL-4 responsiveness. These data indicate that the induction of IL-2 and IL-4
      responsiveness requires different sets of activation signals which can be induced
      by stimulating different epitopes in the CD3-TCR complex. This supports the
      concept that distinct activation pathways are coupled to the CD3-TCR complex.

PMID- 1371525
TI  - Diversity in fine specificity and T cell receptor usage of the human CD4+
      cytotoxic T cell response specific for the immunodominant myelin basic protein
      peptide 87-106.
AB  - Multiple sclerosis (MS), a human demyelinating disease, is thought to be caused
      by an autoimmunologic process, and myelin basic protein (MBP) is considered a
      likely autoantigen. Studies of T cell lines (TCL) responding to different parts
      of the MBP molecule have indicated that amino acids 87 through 106 contain an
      immunodominant epitope of MBP. We have demonstrated previously that amino acids
      89 through 99 represent the core of this 87-106 peptide epitope. Importantly,
      this epitope is not only encephalitogenic in SJL/J mice and Lewis rats but also
      has been shown to be recognized by human cytotoxic TCL in the context of four HLA
      DR molecules that are associated with MS in different geographic areas. If the
      immune response to MBP peptide 87-106 was homogeneous with respect to epitope
      specificity and TCR usage, specific immunotherapies targeting the interaction of
      peptide, MHC, and TCR might be possible. In this study, the fine specificity of
      29 CD4+ cytotoxic, long term, and limiting dilution TCL that had been generated
      against whole MBP and were derived from four MS patients and two healthy
      relatives was dissected using truncated and alanine-substituted peptides for the
      87-106 peptide. In addition, the TCR alpha and beta chain usage of 15 CD4+ TCL
      was determined. Using truncated peptides, the presence of several nested
      immunogenic epitopes within amino acids 87 to 106 was demonstrated. TCL with
      identical restriction elements and similar responses to truncated peptides could
      be differentiated further using alanine-substituted peptides. Finally,
      heterogeneity of TCR usage was shown not only for those lines that differed in
      their peptide specificity but also for some that showed identical responses and
      were restricted by the same HLA-DR antigen. In conclusion, the CD4+ cytotoxic T
      cell response to the immunodominant MBP peptide 87-106 demonstrates a high degree
      of heterogeneity at the level of fine specificity and TCR usage. These findings
      indicate that specific immunotherapies aimed at TCR in MS will probably be more
      complicated than previously anticipated.

PMID- 1371526
TI  - Evidence for recent as well as long term activation of T cells migrating through
      endothelial cell monolayers in vitro.
AB  - As T cells actively extravasate from blood, they adhere to endothelium and then
      migrate out of the vessel with a locomotive activity. Although both adhesion and
      locomotion are properties associated with activated T cells, the two processes
      are not necessarily associated with identical activation states. Using human
      endothelial cells (EC) cultured to confluence on collagen gel, we examined the
      activation state of human peripheral blood T cells that adhere to and migrate
      through EC monolayers with three different methods: flow cytometric analysis of
      cell surface activation-related molecules, incorporation of tritiated nucleotide,
      and cell cycle analysis. The results were as follows. 1) Although expression of
      very late activation Ag integrins VLA-2 and VLA-3 by the initial blood T cell
      population (unseparated cells) and of adherent T cells was minimal, 40 to 45% of
      migrating cells were positive for VLA-2 and VLA-3. 2) The percentage of IL-2R+
      cells in both unseparated and adherent cells was below 5% whereas the percentage
      of IL-2R+ cells among the migrating cells was 22 +/- 9% (range, 12 to 31%, n =
      6). 3) Migrating cells expressed the highest CD26, whereas CD26 of adherent
      (nonmigrating) cells was divided into negative and high expression; in contrast,
      leukocyte adhesion molecule-1 (L-selectin) of both adherent and migrating cells
      was mostly low or negative. 4) [3H]Uridine incorporation of migrating and
      adherent cells was 2.1- to 2.5-fold and 1.4- to 1.7-fold higher, respectively,
      than that of unseparated cells, indicating that RNA synthesis of migrating cells
      as well as adherent cells was enhanced. 5) Cell cycle analysis showed that 23.5%
      of migrating cells appeared to enter the G1 phase but not S or G2 + M phases
      whereas 2.2% of unseparated cells and 8.0% of adherent cells that did not migrate
      had an RNA content consistent with entry into G1. These results suggest that
      cells migrating from normal human blood through unactivated EC have been
      activated recently as well as showing evidence of long term activation. The
      activation state of migrating cells is consistent with the hypothesis that
      previous in vivo activation is required for cells to migrate through EC in this
      system.

PMID- 1371527
TI  - Synthetic peptides anchor T cell-specific TNP epitopes to MHC antigens.
AB  - Several TNP-specific, H-2Kb-restricted mouse CTL clones were identified which
      specifically lysed target cells in the presence of tryptic digests of TNP
      modified BSA. Glutaraldehyde fixation of cells revealed that the tryptic
      fragments did not require further cellular processing. Chromatographic
      fractionation of digested TNP-BSA identified the peptide TNP-BSA222-231,
      containing a TNP-modified lysine at BSA position 227, as the antigenic entity.
      The corresponding synthetic peptide was immunologically cross-reactive with the
      digest. All clones reactive with TNP-BSA222-231 cross-reacted with a similar
      peptide from mouse serum albumin (TNP-MSA126-135), favoring the assumption that
      TNP-BSA222-231 represents an artificial determinant, cross-reacting with some as
      yet unidentified, TNP-modified, Kb-associated self-peptides. Some of our clones
      also cross-reacted with tryptic digests of TNP-OVA or TNP-keyhole limpet
      hemocyanin. We interpret these findings to indicate that 1) a significant
      proportion of hapten (TNP) determinants for T cells are anchored to MHC via
      peptides; and 2) the amino acid sequence of these peptides may only partly define
      the specificity of the T cell-relevant hapten epitope, implying a particularly
      repetitive nature of these determinants. The production of T cell-antigenic
      hapten-peptide conjugates will hopefully open new roads to study immune responses
      to environmental allergens.

PMID- 1371528
TI  - Cleavage of the cell-surface O-sialoglycoproteins CD34, CD43, CD44, and CD45 by a
      novel glycoprotease from Pasteurella haemolytica.
AB  - The study of structural/functional characteristics of the cell-surface
      glycoproteins of leukocytes has led to a better understanding of the
      differentiation and maturation of hematopoietic cells. We have assessed the
      ability of a unique metalloprotease that is secreted by the bovine fibrinous
      pneumonia pathogen Pasteurella haemolytica, to cleave cell-surface glycoproteins
      expressed on human leukocytes. Biochemical analysis shows that the O-glycosylated
      cell surface Ag CD34, CD43 (leukosialin), CD44 (hyaluronic acid receptor), and
      CD45 (leukocyte common Ag), are all cleaved by this protease. Although these
      enzyme-sensitive structures contain N-linked glycans, they are all extensively
      glycosylated with O-linked carbohydrates, which are especially abundant on CD34
      and CD43. In contrast, the glycoproteins CD18/11a,b,c (leukocyte integrins), CD71
      (transferrin receptor), HLA class I, and 8A3 Ag, which contain N-linked glycans
      but no O-sialo-glycans, were resistant to the action of the enzyme. Inasmuch as
      previous studies using glycophorin A had indicated that the substrate specificity
      of this enzyme may be uniquely restricted to the cleavage of O
      sialoglycoproteins, we have designated this activity, P. haemolytica
      glycoprotease. Immunofluorescence analysis with a variety of antibodies to
      different epitopes of the P. haemolytica glycoprotease-sensitive structures
      indicate that this enzyme may have widespread applications in epitope-mapping
      studies, and represents a novel tool with which to study structure/function
      relationships for O-sialoglycosylated cell-surface proteins. However, most
      significantly these results suggest that the P. haemolytica glycoprotease may be
      of use in the affinity purification and recovery of clinically important
      leukocyte subsets, such as primitive hematopoietic progenitors that express CD34.

PMID- 1371529
TI  - "Universal" T helper cell determinants enhance immunogenicity of a Plasmodium
      falciparum merozoite surface antigen peptide.
AB  - Synthetic peptide constructs containing a limited number of epitopes are being
      currently investigated as subunit vaccines against a variety of pathogens.
      However, because of widespread nonresponsiveness to most such constructs,
      possibly attributable to MHC restriction, the choice of appropriate carrier
      molecules to enhance immunogenicity of peptides constitutes an important and
      essential aspect of designing synthetic immunogens for human use. Widely used
      vaccines such as tetanus toxoid (TT) have not been uniformly effective as carrier
      proteins because of the phenomenon of epitope-specific suppression in which
      induction of an immune response against a synthetic peptide conjugated to TT is
      prevented by preexisting immunity to TT. Recently, T cell determinants that can
      be recognized in the context of several class II MHC molecules have been
      identified in tetanus toxin as well as in the circumsporozoite protein of a human
      malarial parasite, Plasmodium falciparum. Such determinants can be potentially
      used to circumvent the problem of epitope-specific suppression. In the present
      study we evaluated two such T cell determinants, viz., tt830-844 from tetanus
      toxin and CST3 from the malarial parasite, for their ability to help induce a
      boostable antibody response and to overcome genetic nonresponsiveness to a
      synthetic 20-residue construct containing a B cell and an overlapping T cell
      epitope from a major merozoite surface protein of P. falciparum. Our data provide
      support for the view that widely recognized T cell determinants may be used as
      universal carrier molecules for general vaccination.

PMID- 1371530
TI  - Monoclonal autoantibodies to subnucleosomes from a MRL/Mp(-)+/+ mouse.
      Oligoclonality of the antibody response and recognition of a determinant composed
      of histones H2A, H2B, and DNA.
AB  - MRL/Mp(-)+/+ mice produce antinuclear antibodies and develop a spontaneous
      autoimmune syndrome with lupus-like nephritis. We obtained a panel of seven
      histone-reactive IgG mAb from a single MRL/Mp(-)+/+ mouse. These antibodies do
      not react significantly with DNA or individual histones, but bind strongly to the
      histone H2A-H2B dimer and even more strongly to the H2A-H2B-DNA complex. These
      antibodies also bind to whole nuclei when tested by immunofluorescence,
      indicating that they recognize an epitope accessible in chromatin. The V region
      sequences of these antibodies have been determined. The H chain third
      complementarity-determining regions of these antibodies are similar to those
      found in anti-DNA antibodies even though the antibodies in our panel do not react
      with DNA in the absence of histones, suggesting that DNA is part of the
      subnucleosome epitope. Several of these antibodies are clonally related,
      supporting the hypothesis that the activation of these clones is Ag-driven.
      Analysis of the sequences of these antibodies indicates that they derive from
      autoreactive B cells that were clonally expanded and whose V region genes have
      undergone numerous somatic mutations.

PMID- 1371531
TI  - Specific endotoxic lipopolysaccharide-binding receptors on murine splenocytes:
      III. Binding specificity and characterization.

PMID- 1371532
TI  - A new method for detachment of Dynabeads from positively selected B lymphocytes.
AB  - This paper describes a method for the detachment of immunomagnetic beads from
      positively selected human B lymphocytes. After rosetting of B cells using anti
      CD19 coated magnetic beads (Dynabeads M-450 Pan B, Dynal), the Dynabeads were
      rapidly detached (efficiency 80%) from the cells using goat anti-mouse-Fab
      antiserum (DETACHaBEAD, Dynal) at ambient temperature. Isolated B cells did not
      show significant differences in the expression of a number of B cell antigens
      when compared to B cells stained in fresh whole blood. In contrast, positively
      selected B cells that had detached from the beads following overnight incubation,
      demonstrated a significantly reduced expression of certain of the antigens
      examined (CD19, CD20 and CD23). It was further demonstrated that neither anti
      CD19 nor anti-Fab resided on the surface of the cells after detachment. The cells
      were still in G0 phase (greater than 90%) at the end of the isolation procedure.
      Moreover, anti-IgM antibodies stimulated the vast majority of the cells to leave
      the G0 phase, and to progress through S phase in the presence of growth factors.
      The cells could also be stimulated to differentiate, further confirming the
      normal functional capacity of the isolated cells. The method described in this
      paper can also be used for the detachment of other positively selected cells,
      such as CD4+ T cells, CD8+ T cells and CD34+ stem cells.

PMID- 1371533
TI  - Physical separation of ICAM-1 binding cells.
AB  - Studies of interactions between specific molecules involved in adhesion between
      cells are often complicated since cells possess many different types of surface
      molecules influencing adhesion. To be able to further study interactions between
      the adhesive cell surface molecule LFA-1 and its ligand ICAM-1, we have produced
      an ICAM-1 fusion protein in which the extracellular part of ICAM-1 has been fused
      to a part of an IgG heavy chain. The fusion protein was produced by CHO cells and
      was easily purified in large quantities from the cell culture supernatant. The
      protein was coupled to magnetic beads and was shown to have binding
      characteristics similar to native ICAM-1. The coupled beads were used for
      magnetic isolation of ICAM-1 binding cells thereby providing a method for
      detecting changes in avidity for ICAM-1 and also for the analysis of ICAM-1
      binding cells.

PMID- 1371534
TI  - Viral culture and p24 antigenemia of human immunodeficiency virus (HIV)-infected
      individuals correlated with antibody profiles determined with recombinant
      polypeptides of all HIV-1 open-reading frames.
AB  - The association between viral activity and antibody profiles was investigated in
      202 individuals infected by the human immunodeficiency virus (HIV) grouped
      according to their Walter Reed clinical stage. Each study group was subdivided
      into subjects positive or negative for markers of active viral replication:
      presence of serum p24 antigen and viral culture. In Western blots using
      recombinant antigens, sera of HIV-positive individuals with positive viral
      markers had a significantly lower antibody reactivity to several viral proteins
      than did individuals without viral markers. Noticeably, proteins of the gag (p24,
      p17) and env (gp120, COOH-terminal part of gp41) open-reading frames revealed a
      decreased reactivity. The antibody response to the regulatory proteins revealed
      no or poor association with viral activity in the host. The results suggest that
      seroreactivity is mainly influenced by factors reflecting the viral activity of
      an HIV-infected individual, while the clinical stage of the patient is less
      important. Especially, reductions in antibodies against gp120 and p17 were useful
      markers associated with increased viral activity.

PMID- 1371535
TI  - Inhibition of human T cell leukemia virus by the plant flavonoid baicalin (7
      glucuronic acid, 5,6-dihydroxyflavone).
AB  - The ability of baicalin (7-glucuronic acid, 5,6-dihydroxyflavone), a flavonoid
      compound purified from the Chinese medicinal herb, Scutellaria baicalensis
      georgi, to inhibit human T cell leukemia virus type I (HTLV-I) was examined.
      Baicalin produced concentration-dependent inhibition of HTLV-I replication in
      productively infected T and B cells. Moreover, baicalin treatment selectively
      reduced the detectable levels of HTLV-I p19 gag protein in infected cells by
      greater than 70% at concentrations that produced insignificant effects on total
      cellular protein and DNA synthesis with no loss in cell viability. Resistance to
      HTLV-I infection and virus-mediated transformation was noted in uninfected
      peripheral blood lymphocytes pretreated with baicalin before cocultivation with
      lethally irradiated chronically infected cells. Baicalin inhibited reverse
      transcriptase activity in HTLV-I-infected cells as well as the activity of
      purified reverse transcriptase from Moloney murine leukemia virus and Rous
      associated virus type 2. These results suggest that baicalin may be a potential
      therapeutic agent against HTLV-I-associated T cell diseases.

PMID- 1371536
TI  - Inhibition of endotoxin-induced macrophage tumor necrosis factor expression by a
      prostacyclin analogue and its beneficial effect in experimental
      lipopolysaccharide intoxication.
AB  - Tumor necrosis factor (TNF), a protein produced in large quantities by endotoxin
      activated macrophages, has been implicated as an important mediator of the lethal
      effect of endotoxin. A stable prostacyclin analogue (iloprost) was investigated
      for its ability to interfere with TNF secretion of lipopolysaccharide (LPS)
      stimulated macrophages. It could be demonstrated by bioassays that LPS-induced
      TNF production was suppressed in a dose-dependent manner when macrophages were
      treated with iloprost at the time of LPS stimulation. Northern blot analysis
      revealed that iloprost inhibited TNF production at the transcription level. In
      vivo, endotoxin-induced mortality rates in galactosamine-sensitized mice could be
      significantly (P less than .05) reduced by iloprost administration. It is assumed
      that prostacyclin modulates endotoxin-induced and TNF-mediated inflammation in
      septic shock.

PMID- 1371537
TI  - Relative frequency of nonneutralizing antibodies to interferon (IFN) in hepatitis
      patients treated with different IFN-alpha preparations.

PMID- 1371538
TI  - Reactivity to c33c antigen as a marker of hepatitis C virus multiplication.

PMID- 1371539
TI  - The topography of the surface of potato virus X: tritium planigraphy and
      immunological analysis.
AB  - Thermally activated tritium atoms were used to probe the surface topography of
      the coat protein of potato virus X (PVX) potexvirus. The accessibility profile of
      amino acid residues in the polypeptide chain was determined from data on the
      intramolecular distribution of tritium label in the PVX coat protein. Tryptic
      peptides T1 and T2, as well as parts of peptides T3 and T5, from the PVX
      particles were all located in the N-terminal region of the PVX coat protein and
      were accessible to tritium labelling, whereas the C-terminal region of the coat
      protein was practically inaccessible to it. Indirect ELISA and immunoblotting
      with two PVX-specific monoclonal antibodies confirmed that the N terminus of the
      coat protein (residues 1 to 56) was exposed on the virus surface, and furthermore
      that this region forms a highly immunogenic virus-specific antigenic region. The
      data obtained support the spatial model of PVX, in which the N-terminal amino
      acids of the coat protein are exposed at the particle surface, and the C-terminal
      region is buried in the particle. The spatial organization of the PVX coat
      proteins differs from the model proposed for other filamentous plant viruses such
      as potyviruses and tobamoviruses where both the N and C termini of the coat
      protein are located at the particles' surface.

PMID- 1371540
TI  - Hexamethylene bisacetamide stimulates herpes simplex virus immediate early gene
      expression in the absence of trans-induction by Vmw65.
AB  - Hexamethylene bisacetamide (HMBA) and DMSO are known to induce differentiation of
      cultured erythroleukaemic cells and to enhance the reactivation of latent herpes
      simplex virus (HSV) after explantation of ganglia. We report that the presence of
      these compounds in cell culture medium overcomes the replication defect of
      in1814, an HSV-1 mutant with an insertion mutation that inactivates the virion
      trans-inducing factor, Vmw65 (VP16). The effect of HMBA was not cell type
      specific and was attained even by a short exposure (1.5 to 5 h) to the agent
      early after infection. The presence of HMBA resulted in an increase in immediate
      early (IE) RNA accumulation after infection of cells in the presence of
      cycloheximide, such that RNA levels in in1814-infected cells approached the
      values observed in wild-type HSV-1-infected cells in the absence of HMBA.
      Transport of viral DNA to the cell nucleus was not affected by HMBA. The results
      suggest that HMBA- and DMSO-mediated enhancement of reactivation from latency is
      due to an increase in IE RNA production. In addition, these studies demonstrate a
      primary effect of HMBA on gene regulation which may be a paradigm for initial
      events during erythroleukaemic cell differentiation.

PMID- 1371541
TI  - Canine parvovirus empty capsids produced by expression in a baculovirus vector:
      use in analysis of viral properties and immunization of dogs.
AB  - The VP-2 genes of canine parvovirus (CPV) and a recombinant consisting of CPV and
      feline panleukopenia virus (FPV) sequences were cloned into baculovirus
      expression vectors, fused to the baculovirus polyhedrin promoter. Recombinant
      baculoviruses were prepared and the properties of the parvovirus proteins
      expressed in insect cells examined. The proteins produced were the same size as
      the authentic CPV VP-2 protein, and were produced late after infection; the
      quantity of proteins recovered from the insect cell cultures was similar to those
      produced in CPV infections. Parvovirus particles formed had the haemagglutination
      (HA), sedimentation and buoyant density properties of authentic CPV capsids. Both
      the CPV capsids and the CPV-FPV recombinant capsids from the baculovirus system
      expressed the same epitopes as those seen in the viable parvoviruses when tested
      with a panel of anti-parvovirus monoclonal antibodies. Lysates of recombinant
      baculovirus-infected cells were inoculated into dogs, giving rise to serum
      neutralizing and HA-inhibiting antibodies, and the immunized dogs were protected
      from clinical disease upon challenge with a virulent isolate of the most recent
      antigenic type of CPV.

PMID- 1371542
TI  - Protection of mice from lethal influenza by defective interfering virus: T cell
      responses.
AB  - The immune-mediated lethal influenza in C3H/He-mg (H-2k) mice infected with A/WSN
      influenza virus (H1N1) was investigated. A primary class I major
      histocompatibility complex-restricted, CD8+ cytotoxic T lymphocyte (CTL) response
      was found in the lungs with a peak activity at 5 days post-infection. Monoclonal
      antibody depletion in vivo showed that a lethal CD8+ cell response as well as a
      lethal CD4+ response was generated during infection. Mice survived infection only
      if both CD8+ and CD4+ cells were depleted. Mice infected with the same dose of
      virus, but treated with defective interfering (DI) A/WSN virus develop only a
      transient sub-lethal respiratory disease even though multiplication of virus in
      the lungs is undiminished, and we have shown here that this correlates with a
      reduction in the local CTL response. The mechanism by which DI virus beneficially
      modulates the immune response is discussed; it is proposed that there is
      classical, but cell type-specific DI virus interference in lymphocytes but not in
      the cells of the lung in which virus multiplies productively.

PMID- 1371543
TI  - Human immunodeficiency virus type 1 envelope glycoprotein gp120-mediated killing
      of human haematopoietic progenitors (CD34+ cells).
AB  - The effects of human immunodeficiency virus type 1 (HIV-1) and recombinant
      envelope glycoprotein gp120 on the in vitro growth of enriched human
      haematopoietic progenitors (CD34+ cells) have been investigated. A 2 h exposure
      to HIV-1 resulted in a progressive and significant reduction of viable CD34+ cell
      number in liquid cultures and of granulocyte-macrophage, erythroid and
      megakaryocytic progenitors in semisolid cultures. In virus-treated CD34+ cells,
      no signs of active virus replication were observed and the possibility of latent
      infection was excluded by quantitative polymerase chain reaction. Recombinant HIV
      1 envelope glycoprotein gp120 added to CD34+ cell cultures displayed a dose
      dependent inhibitory activity on CD34+ cell viability. Neutralizing antibody
      against gp120 was able to block completely the inhibitory activity on CD34+ cells
      of either HIV-1 or recombinant gp120. These results demonstrate that HIV-1
      envelope glycoprotein gp120 has a direct cytotoxic effect on CD34+ cells.

PMID- 1371545
TI  - The direct effects of graded axonal compression on axoplasm and fast axoplasmic
      transport.
AB  - The direct effects of mechanical compression on axoplasm and fast axoplasmic
      transport were studied by video-enhanced differential interference microscopy.
      Single axons, isolated from the squid, were compressed with 0.5, 5, 20, or 100
      gram (g) weights placed over a 1 millimeter (mm) length of axon. Brief
      compressions (10 seconds) at low pressures (0.5 g/mm) momentarily deformed the
      axon, but the axoplasm and axon returned to their normal shape and position after
      the pressure was removed, and no residual changes in axoplasmic structures, fast
      axoplasmic transport or membrane function were seen. Compressing the axon with 5
      20 g/mm, however, broke the axoplasm at the site of the crush and squeezed the
      axoplasm out from under the compression site. Though the axoplasm usually
      returned to the crush site after the weight was removed and organelles continued
      to move in the axoplasm under the crush, the organelles failed to cross a dense
      line that marked the site of the rejoined axoplasm, instead they accumulated over
      time at the crush site. This results suggests that the blockage of fast transport
      at moderate compressions was due to a mechanical breakage of the axoplasm at the
      compression site. The plasma membrane was apparently not transected after
      moderate compressions (5-20 g/mm) since the resting membrane potential returned
      to nearly control levels after the weight was removed. Compressions with 100
      g/mm, however, did break the plasma membrane as evidenced by the rapid and
      irreversible loss of the action potential and resting potential and the ion
      dependent liquefaction of axoplasm and loss of all organelle transport at the 100
      g/mm compression site. Thus, small mechanical pressure elastically deformed the
      axoplasm, moderate pressures mechanically broke the axoplasm, and high pressures
      broke the axoplasm and the plasma membrane.

PMID- 1371544
TI  - Epitope mapping of the human papillomavirus type 16 E4 protein by means of
      synthetic peptides.
AB  - Eight overlapping icosapeptides covering the entire sequence of the E4 protein of
      human papillomavirus type 16 (HPV-16), were prepared and tested for their
      reactivity with human sera in IgG-specific ELISA. The strongest reactivity of
      sera from HPV-16 DNA-positive invasive cervical carcinoma (INCA) patients was
      detected with the peptide denoted 16/E4-6, covering amino acids 51 to 70.
      Subsequently nearly 200 sera were tested for the presence of the 16/E4-6-specific
      antibody. Reactivity was more frequent in cervical intraepithelial neoplasia
      patients and INCA patients than in matched control subjects. Sera from INCA
      patients were also tested for antibody reactive with peptide 16/E7-2 covering the
      major type-specific reactive region of the HPV-16 E7 protein. Only four of 13
      sera possessing the 16/E4-6-specific antibody were reactive with the 16/E7-2
      peptide.

PMID- 1371546
TI  - Cystic fibrosis: beyond the gene to therapy.

PMID- 1371547
TI  - Pathophysiology of pelvic adhesions. Modern trends in preventing infertility.
AB  - Infertility is secondary to pelvic adhesions in 15-20% of cases. Pelvic adhesions
      result from pelvic inflammatory disease, previous pelvic surgery, foreign bodies
      and previous appendicitis with pelvic abscess. As a result of the insult to the
      peritoneal surfaces of the pelvic organs, the concentrations of peritoneal fluid
      leukotriene, B4 and prostaglandin E2 are increased. Also, there is a decrease in
      plasminogen activity. The end result will be the formation of fibrin deposits,
      which will end in the formation of pelvic adhesions. The diagnosis of adhesions
      can be achieved by a high index of suspicion in patients with a history of pelvic
      infections or surgery. A pelvic examination with fixation of the uterus and/or
      adnexa is also highly suggestive. A hysterosalpingogram might lead to a suspicion
      of the presence of pelvic adhesions; however, there is some degree of false
      positive and -negative results. The definitive diagnosis depends on laparoscopy.
      The use of an internationally accepted classification, such as that of the
      American Fertility Society, allows investigators to compare the results of
      treatment. Various adjuvants have been used following lysis of adhesions to
      prevent their recurrence; they yield various results. The most significant
      recommendation is to prevent the occurrence of adhesions by following the
      principles of microsurgical technique during every surgical procedure.

PMID- 1371548
TI  - Membrane topology and quaternary structure of cardiac gap junction ion channels.
AB  - The membrane topology and quaternary structure of rat cardiac gap junction ion
      channels containing alpha 1 connexin (i.e. Cx43) have been examined using anti
      peptide antibodies directed to seven different sites in the protein sequence,
      cleavage by an endogenous protease in heart tissue and electron microscopic image
      analysis of native and protease-cleaved two-dimensional membrane crystals of
      isolated cardiac gap junctions. Specificity of the peptide antibodies was
      established using dot immunoblotting, Western immunoblotting, immunofluorescence
      and immunoelectron microscopy. Based on the folding predicted by hydropathy
      analysis, five antibodies were directed to sites in cytoplasmic domains and two
      antibodies were directed to the two extracellular loop domains. Isolated gap
      junctions could not be labeled by the two extracellular loop antibodies using
      thin-section immunogold electron microscopy. This is consistent with the known
      narrowness of the extracellular gap region that presumably precludes penetration
      of antibody probes. However, cryo-sectioning rendered the extracellular domains
      accessible for immunolabeling. A cytoplasmic "loop" domain of at least Mr = 5100
      (residues (101 to 142) is readily accessible to peptide antibody labeling. The
      native Mr = 43,000 protein can be protease-cleaved on the cytoplasmic side of the
      membrane, resulting in an Mr approximately 30,000 membrane-bound fragment.
      Western immunoblots showed that protease cleavage occurs at the carboxy tail of
      the protein, and the cleavage site resides between amino acid residues 252-271.
      Immunoelectron microscopy demonstrated that the Mr approximately 13,000 carboxy
      terminal peptide(s) is released after protease cleavage and does not remain
      attached to the Mr approximately 30,000 membrane-bound fragment via non-covalent
      interactions. Electron microscopic image analysis of two-dimensional membrane
      crystals of cardiac gap junctions revealed that the ion channels are formed by a
      hexagonal arrangement of protein subunits. This quaternary arrangement is not
      detectably altered by protease cleavage of the alpha 1 polypeptide. Therefore,
      the Mr approximately 13,000 carboxyterminal domain is not involved in forming the
      transmembrane ion channel. The similar hexameric architecture of cardiac and
      liver gap junction connexins indicates conservation in the molecular design of
      the gap junction channels formed by alpha or beta connexins.

PMID- 1371549
TI  - ME491 melanoma-associated glycoprotein family: antigenic identity of ME491, NKI/C
      3, neuroglandular antigen (NGA), and CD63 proteins.
AB  - BACKGROUND: Numerous monoclonal antibodies (MAbs) have been produced to antigens
      found in human melanomas. Three of the best characterized melanoma antigens
      include the melanoma-associated glycoproteins (MAGs) defined by two reagent
      families--the ME491 family (including ME491, 8-1H, and 8-2A) and the NKI/C-3
      family (including NKI/C-3 and NKI/black-13)--as well as the neuroglandular
      antigen (NGA) defined by MAbs LS59, LS62, and LS140. These three antigens have
      significant similarities in tissue distribution, biosynthesis, and structure. The
      ME491 MAG has been cloned, mapped, and sequenced. Numerous non-melanoma
      associated proteins (Sm23, CO-029, R2, TAPA-1, CD9, CD37, CD53, and CD63) have
      recently been shown to have significant homology to this sequence. PURPOSE: We
      conducted this study to investigate the similarity between the two MAG antigens
      and NGA. METHODS: Several reagents defining the three different melanoma antigens
      were compared, using competition immunoprecipitation, immunoassay, and inhibition
      radioimmunoassay techniques. RESULTS: Immunoassay experiments show that MAbs
      defining the three melanoma antigens bind to affinity-purified ME491 antigen and
      inhibit each other from binding in an inhibition radioimmunoassay. Competition
      immunoprecipitation experiments demonstrate that the ME491 and NKI/C-3 antibodies
      bind to NGA. Rabbit anti-ME491 idiotype serum recognizes determinants shared by
      NKI/C-3 and the anti-NGA MAbs. A competition immunoprecipitation experiment also
      confirms the identity of CD63, as defined by MAb RUU-SP 2.28, with the three
      melanoma antigens. CONCLUSION: These data indicate that the MAGs defined by ME491
      and NKI/C-3 as well as the anti-NGA antibodies are epitopes of the same molecule,
      which is identical to CD63 by both immunochemical and molecular genetic
      investigations. IMPLICATIONS: Our results indicate that the data obtained in
      studies of these three melanoma antigens may be pooled, and we propose that the
      molecule recognized by these reagents be classified as CD63.

PMID- 1371550
TI  - Randomized double-blind study comparing the effectiveness of balloon dilation of
      the prostate and cystoscopy for the treatment of symptomatic benign prostatic
      hyperplasia.
AB  - We attempted to determine the effectiveness of balloon dilation of the prostate
      for the treatment of symptomatic benign prostatic hyperplasia (BPH). A total of
      33 men with symptomatic BPH signed informed consent to participate in a
      randomized, double-blind study comparing balloon dilation of the prostate and
      cystoscopy. Balloon dilation of the prostate and cystoscopy were performed with
      the patient under intravenous sedation after intraurethral instillation of
      viscous lidocaine and infiltration of the autonomic neural innervation of the
      prostate with 1% lidocaine. Efficacy was based upon improvement in Boyarsky
      symptom scores, increases in peak urinary flow rates and patient global
      assessment of symptomatic improvement. Efficacy was assessed at 1 and 3 months
      after treatment. A study nurse blinded to the randomization scheme administered
      the symptom score questionnaires and supervised the uroflowmetry studies. The
      study was randomized, since the mean baseline prostate sizes, peak urine flow
      rates, obstructive and irritative symptoms scores, post-void residual volumes and
      patient ages were similar in the 2 groups. The patient perceptions of treatment
      rendered were similar for the 2 treatment groups, confirming that the study was
      double-blind. The patients undergoing cystoscopy and balloon dilation of the
      prostate experienced a statistically significant improvement in the mean total
      symptom scores at 1 and 3 months. The mean total symptom scores after balloon
      dilation of the prostate and cystoscopy at 1 and 3 months were not significantly
      different. The mean peak urinary flow rates 1 and 3 months after balloon dilation
      of the prostate and cystoscopy were not significantly different from the baseline
      mean peak urinary flow rates. We demonstrate that balloon dilation of the
      prostate and cystoscopy are equally effective for the treatment of BPH. Since
      cystoscopy is considered a diagnostic modality, our study suggests that the
      efficacy previously observed after balloon dilation of the prostate is primarily
      placebo-related. The study does not support the indication of balloon dilation of
      the prostate for the treatment of symptomatic BPH.

PMID- 1371551
TI  - The intraprostatic spiral: clinical results in 150 consecutive patients.
AB  - The clinical results of treatment of infravesical prostatic obstruction with an
      intraurethral coil in 150 consecutive patients are reported. A total of 80
      patients had urinary retention and 70 had severe prostatism. Median observation
      time was 8.2 months, with a range of 0 to 40 months. In 75 patients the spiral
      was removed after a median of 4 months (range 0 to 30 months) because of planned
      prostatectomy in 17, urinary retention in 16, incontinence in 10, local
      discomfort in 7, no symptomatic improvement in 13 and causes not related to the
      spiral (stroke and so forth) in 7. Migration occurred 55 times in 42 patients but
      this only led to coil removal in 5. A total of 23 patients died with the coil in
      situ. Voiding symptoms improved considerably in the majority of the patients.
      Approximately two-thirds of the patients had no or few symptoms, while a fourth
      had moderate symptoms, leaving only approximately 10% with severe prostatism.
      Chronic bacteriuria was noted in 52 patients but was not a clinical problem.
      Calcification on the top and inside of the coil was noted mainly after long-term
      treatment, and probably necessitated exchange of the coil after 2 to 3 years. We
      conclude that the prostatic spiral is a useful alternative to an indwelling
      catheter. However, life-long followup is necessary in most patients.

PMID- 1371552
TI  - Nuclear localization of androgen receptor in heterogeneous samples of normal,
      hyperplastic and neoplastic human prostate.
AB  - To facilitate an understanding of how androgens participate in the genesis of
      human benign hyperplasia and carcinoma we assayed androgen receptor in the
      epithelium and stroma of human prostatic tissue from 57 patients.
      Immunohistochemical staining of human androgen receptor was performed on 106
      sections of normal prostate, benign prostatic hyperplasia (BPH) and prostate
      cancer. To determine variability of androgen receptor staining sections taken
      from different portions of the gland were studied. Frozen tissue sections were
      incubated with monoclonal antiandrogen receptor antibodies and staining was
      completed by the indirect avidin-biotin peroxidase method. Antibody staining was
      found mainly in the nucleus of prostatic epithelial cells, although some stromal
      cells also showed positive staining. Unlike normal prostate, there was a
      heterogeneous distribution of androgen receptor in BPH and prostate cancer. The
      androgen receptor content in well differentiated adenocarcinoma epithelium was
      significantly higher compared to moderately (p less than 0.05) and poorly (p less
      than 0.05) differentiated adenocarcinoma. Regardless of the origin of stromal
      tissue, some staining was observed. In each specimen studied the androgen
      receptor staining was consistent qualitatively and quantitatively for each
      pathological component throughout the specimen. These data confirm that androgen
      receptor is a nuclear receptor protein. Furthermore, they show the ability of
      monoclonal antibodies to reveal cellular/subcellular distribution of androgen
      receptor, and demonstrate a correlation between the degree of tumor
      differentiation and androgen receptor content in epithelial but not in stromal
      cells. These observations may have important implications for understanding the
      variable tumor response to hormone therapy.

PMID- 1371553
TI  - Effects of rectal examination, prostatic massage, ultrasonography and needle
      biopsy on serum prostate specific antigen levels.
AB  - Measurement of serum prostate specific antigen (PSA) is commonly used to evaluate
      the prostate gland in a variety of clinical settings. We examined the effects of
      prostatic manipulations, including digital rectal examination, prostate massage,
      transrectal ultrasonography and transrectal needle biopsy, on serum PSA levels in
      199 men. We detected no clinically significant difference between serum PSA
      levels obtained immediately before and at 5 or 90 minutes after rectal
      examination in 43 men. We observed falsely increased PSA levels (to greater than
      4 ng./ml., Tandem-R) in 1 of 17 men (6%) following prostatic massage and in 3 of
      27 men (11%) following ultrasonography. Transrectal needle biopsy caused an
      immediate increase in serum PSA in 92 of 100 men. In 29 of these 92 men (32%)
      when followed weekly serum PSA levels did not return to baseline as expected
      according to the published serum PSA half-life of 2 to 3 days. Biopsies taking 3
      or fewer cores (7 patients) resulted in a smaller increase in serum PSA (mean
      1.63 +/- 1.12 times the baseline level versus 6.24 +/- 1.10 times baseline, p
      less than 0.03) and a proportionally shorter duration of PSA elevation (mean 1.43
      +/- 0.48 weeks versus 2.13 +/- 0.14 weeks, p = 0.20) than those taking 4 or more
      cores (93 patients). Prostate size and the presence of cancer had no influence on
      the duration of PSA elevation following biopsy. We conclude that digital rectal
      examination, prostatic massage and ultrasonography have minimal effects on serum
      PSA levels in most patients. However, prostatic needle biopsy usually causes
      marked elevations of serum PSA levels with a persistent PSA leak into the blood
      stream lasting longer than expected from the serum half-life of PSA in
      approximately 25% of the patients.

PMID- 1371555
TI  - The use of prostate specific antigen density to enhance the predictive value of
      intermediate levels of serum prostate specific antigen.
AB  - Prostate specific antigen (PSA) is an extremely valuable tumor marker. However,
      its use in detection is limited by its low positive and negative predictive
      values. The ability of serum PSA to distinguish between benign and malignant
      prostatic conditions is particularly poor in the intermediate range of 4.1 and 10
      ng./ml. by the Hybritech assay. We used transrectal ultrasound determined
      prostate volumes in a well characterized population of 533 men to form a serum
      PSA/prostate volume ratio called prostate specific antigen density (PSAD). The
      prevalence of cancer in the entire population was 18.4%. Discriminant analysis
      according to negative or positive outcome allowed for the construction of
      nomograms, which resulted in a PSAD defined cancer risk ranging from 3 to 100%.
      Predictive value nomograms created from PSAD may allow for a more individualized
      approach to evaluation of patients with intermediate levels of Hybritech serum
      PSA.

PMID- 1371554
TI  - Prostate specific antigen density: a means of distinguishing benign prostatic
      hypertrophy and prostate cancer.
AB  - Isolated prostate specific antigen (PSA) determinations in asymptomatic
      individuals have not demonstrated sufficient sensitivity and specificity to be
      useful in the routine evaluation of prostate disease. To enhance the accuracy of
      serum PSA we have used a quotient of serum PSA and prostate volume, which we
      refer to as prostate specific antigen density (PSAD). Prostate volume in this
      study was calculated from magnetic resonance imaging determinations of benign
      prostatic hypertrophy (BPH) or from the dimensions of the surgical specimen of
      cancer using the formula, length x width x depth x 0.5 = volume. A total of 61
      patients with prostatic disease clinically confined to the prostate glands (41
      with prostate cancer undergoing radical prostatectomy and 20 with BPH) was
      evaluated. The mean PSAD for prostate cancer was 0.581 while that for BPH was
      0.044 (p less than 0.002). No patient with BPH had a PSAD of greater than 0.117
      and only 1 patient had a density of 0.1 or greater. Of 34 patients with a PSAD of
      0.1 or greater 33 had prostate cancer. Only 2 of the 41 prostate cancer patients
      and 14 of the BPH patients had a PSAD of 0.05 or less. There were 11 patients
      with a PSAD of greater than 0.05 and less than 0.1, including 6 with prostate
      cancer (1 with P0 disease) and 5 with BPH. Of the 6 prostate cancer patients 5
      had a PSA of 4.0 or less and among the 5 patients with BPH 4 had a serum PSA of
      greater than 4.0 and 1 had a PSA of greater than 10. These results suggest that
      PSAD may be useful in distinguishing BPH and prostate cancer.

PMID- 1371556
TI  - Diagnosis of prostate cancer: a personal view.

PMID- 1371557
TI  - Prostate cancer in nonurological patients with normal prostates on digital rectal
      examination.
AB  - Random systematic ultrasonographically guided transrectal core biopsies of the
      prostate were performed in 73 patients with pulmonary malignancies to exclude
      prostate cancer as a primary malignant neoplasm. Of the patients 41 had normal
      prostates as judged by digital rectal examination, 27 had firm prostates and 5
      had clinical stage B nodules. Hypoechoic areas were seen on transrectal
      ultrasonography in 14 of the 41 patients (34%) with normal prostates. Biopsy of
      the hypoechoic areas in this subgroup detected only 1 grade II prostate cancer.
      In another patient with normal transrectal ultrasound grade I cancer was detected
      by mapping of the prostate with 6 systematic ultrasonographically guided
      transrectal core biopsies. Of the remaining 39 patients with normal prostates
      transrectal ultrasound detected no hypoechoic defect in 26, a specificity for the
      detection of prostate cancer of 67%. Multiple core biopsies revealed prostate
      cancer in 15 of the 32 cases of palpably abnormal prostates, including 12 that
      were hypoechoic. Prostate cancer is a rare histopathological finding in men with
      normal prostates on rectal examination. Transrectal ultrasound detected only 1 of
      2 low volume prostate cancers in our study group. Thus, ultrasound seems to have
      little use in patients with prostates that appear normal on digital examination,
      and its specificity is low.

PMID- 1371558
TI  - The distribution of prostate specific antigen in men without clinical or
      pathological evidence of prostate cancer: relationship to gland volume and age.
AB  - We estimated the in vivo prostate gland volume in 408 men (320 without clinical
      evidence of prostate cancer, and 88 with an abnormal digital rectal examination
      and/or transrectal prostate ultrasound and negative biopsies) using sequential
      step-section ultrasound analysis and correlated it to the serum prostate specific
      antigen (PSA) value. Of the men 331 (81.1%) had a PSA value of 4 ng./ml. or less.
      The PSA value was greater than 4 but less than or equal to 10 in 64 men (15.7%)
      and greater than 10 in 13 (3.2%). The men were subclassified by prostate gland
      volume at arbitrary break points. A total of 139 men (34.1%) had a gland of 25
      cm.3 or less, 2.2% of whom had a PSA value of greater than 4. Further analysis
      revealed that the incidence of a PSA value greater than 4 increased as the
      prostate volume increased (18.4% for greater than 25 but less than or equal to
      50, and 65.4% for greater than 50) and as age increased. We found a statistically
      significant association between prostate gland volume and patient age (p less
      than 0.00005) to the serum PSA concentration. The finding of a PSA value of
      greater than 10 was uncommon regardless of the prostate gland volume. Clinical
      implications of these results are discussed, and a statistical model to estimate
      the serum PSA by gland volume and patient age was constructed.

PMID- 1371559
TI  - Screening for prostatic carcinoma with prostate specific antigen.
AB  - Prostate specific antigen (PSA), neutral serine protease secreted exclusively by
      prostatic epithelial cells, has a number of applications in the management of men
      with prostatic carcinoma. While it is widely recognized that elevated PSA
      correlates with the presence of carcinoma, little data exist regarding the use of
      PSA as the initial test in the early detection of prostatic cancer. We measured
      serum PSA levels in men older than 50 years and performed digital rectal
      examination and ultrasound guided prostate biopsy of those who had a PSA level of
      greater than 4.0 ng./ml. A total of 1,249 men entered the protocol, of whom 187
      (15.0%) had PSA levels above 4.0 ng./ml. Digital rectal examination and
      ultrasound guided biopsy were performed at our facility in 105 patients (56.2%).
      A total of 32 carcinomas (30.5%) was detected, including 23 in men with PSA
      between 4.1 and 10.0 ng./ml. and 9 in men with a PSA of greater than 10.0 ng./ml.
      Of the 32 carcinomas 12 (37.5%) occurred in men with normal prostates or glands
      demonstrating only asymmetry on digital rectal examination, and 3 men had
      carcinoma despite normal digital rectal examination and no hypoechoic peripheral
      zone lesion detected on ultrasound. Of the 32 patients 30 had clinically
      localized carcinoma but 7 of the 16 undergoing radical prostatectomy had
      pathological upstaging. We conclude that PSA represents an important adjunct to
      digital rectal examination for the early detection of prostatic carcinoma. The
      efficacy of this or any other early detection test to decrease prostate cancer
      mortality necessitates the results of prospectively randomized clinical trials.

PMID- 1371560
TI  - Serum prostate specific antigen as pre-screening test for prostate cancer.
AB  - Prostate cancer has become the most common cancer and the second cause of death
      due to cancer in men in North America. Since curative therapies are limited to
      early stages of the disease, the availability of an efficient, easy to perform,
      widely acceptable and cost-effective method of early detection of prostate cancer
      is particularly important. Thus, digital rectal examination, transrectal
      ultrasonography of the prostate as well as measurements of serum prostate
      specific antigen (PSA) were performed independently in a series of 1,002 men
      between 45 and 80 years old randomly selected from the electoral rolls of Quebec
      City and its vicinity as part of a screening program for prostate cancer. Using
      this population of randomly chosen men, various cutoff serum PSA values were
      selected in an attempt to find the optimal decision threshold that would indicate
      a much greater risk of having prostatic cancer. At a threshold value of 3.0
      micrograms./l. the sensitivity and specificity of the test are 80.7 and 89.6%,
      respectively, while the area under the receiver operating characteristic curve
      reflecting the accuracy of the test is 87.8 +/- 3.3% (plus or minus standard
      deviation). Moreover, the negative predictive value was estimated at 98.6%, thus
      leaving only a 1.4% chance of missing cancer when the serum PSA value was 3.0
      micrograms./l. or less. Most importantly, such a threshold level of serum PSA
      retains only 19% of the whole cohort as candidates for transrectal
      ultrasonography and expensive diagnostic procedures, thus leading to the finding
      of 1 prostate cancer of 4 such examinations. The present data indicate that
      simple measurement of serum PSA can be used efficiently as a pre-screening test
      for prostate cancer in the general population to identify, at a low cost, the
      subpopulation of men at a much greater risk of having prostate cancer, and who
      should then be submitted to the more elaborate and expensive diagnostic
      procedures.

PMID- 1371561
TI  - The predictive significance of substaging stage A prostate cancer (A1 versus A2)
      for volume and grade of total cancer in the prostate.
AB  - Morphometric analysis was performed on 44 radical prostatectomy specimens for
      clinical stages A1 and A2 carcinoma of the prostate. The majority of stage A
      cancers (86%) were located in the transition zone of the prostate, while only 14%
      arose in the peripheral zone. The subclassification into stages A1 and A2 based
      on the percentage of cancer in the transurethral resection chips did not reliably
      distinguish those cancers of high volume (transurethral resection plus residual).
      All 6 cases with Gleason grade 4 elements in the transurethral resection chips
      had relatively high volume cancer. In 32 of the 44 cases (73%) unsuspected
      cancers unrelated to the tumor detected at transurethral resection were found in
      the radical prostatectomy specimen. Of these cancers 87% were nontransition zone
      tumors. Eight unsuspected cancers were larger than the stage A cancer but only 2
      of them were larger than 1 cc. Post-resection serum prostate specific antigen
      (PSA) levels were elevated with increasing total residual cancer volume in the
      radical specimen. In 19 of 20 cases with a PSA of greater than 2.5 ng./ml. the
      total residual cancer volume was more than 0.9 cc, while in 7 of 8 with a PSA of
      less than 1 ng./ml. total residual tumor volume was lower than 0.4 cc.

PMID- 1371562
TI  - Transrectal ultrasound imaging and ultrasound guided prostate biopsies in the
      detection of residual carcinoma in clinical stage A carcinoma of the prostate.
AB  - Planning treatment for patients diagnosed with stage A prostate cancer by
      transurethral resection or open enucleation can be difficult. Inability to
      determine the presence or absence of significant residual disease can result in
      unnecessary treatment for some individuals and inadequate treatment in others.
      Transrectal ultrasound imaging and systematic prostate biopsies offer a potential
      means of evaluating these patients. To determine the rate of residual cancer
      detection 3 groups of stage A prostate cancer cases were evaluated. Group 1
      consisted of 39 patients who underwent radical prostatectomy. Preoperative
      ultrasound imaging revealed residual cancer in only 24%. Transrectal ultrasound
      guided systematic biopsies were performed in group 2 (25 patients) and revealed
      cancer in only 28%. Based on prior morphometric studies of prostatectomy
      specimens from stage A cases, a modification of the systematic biopsy method,
      which included anteriorly directed biopsies, was developed and applied to group 3
      (47 patients). Cancer was detected in 47% of the patients, and it was detected by
      additional anterior biopsies alone in 11%.

PMID- 1371563
TI  - Luteinizing hormone-releasing hormone downstaging of clinical stage C prostate
      cancer.
AB  - A total of 7 patients with clinical stage C prostate cancer determined by digital
      rectal examination, transrectal ultrasonography, radionuclide bone scanning and
      serum prostatic acid phosphatase determination was treated with luteinizing
      hormone-releasing hormone analogues for 2 to 5 months in an attempt to downstage
      the disease. Although substantial decreases in prostate specific antigen level
      and prostatic volume occurred, only 2 patients experienced pathological
      downstaging of disease. We conclude that luteinizing hormone-releasing hormone
      therapy for downstaging of clinical stage C prostatic cancer is of limited value.

PMID- 1371564
TI  - Estramustine and vinblastine: use of prostate specific antigen as a clinical
      trial end point for hormone refractory prostatic cancer.
AB  - The combination of estramustine phosphate and vinblastine sulfate, 2 agents with
      separate and unique antimicrotubular effects, has demonstrated additive
      cytotoxicity against the DU145 human prostate derived cell line in vitro. We
      evaluated this combination in 25 patients with progressive hormone refractory
      prostate cancer. Of 24 patients with an elevated prostate specific antigen (PSA)
      level at the start of treatment 13 (54%, 95% confidence limits 34 to 74%) had a
      greater than 50% decrease in PSA levels on at least 3 consecutive biweekly
      determinations. The median decrease in PSA in responding patients was 64% (mean
      71.7%) and the median duration of response was 7 months. In 5 patients with
      bidimensionally measurable disease 2 partial responses were observed. Treatment
      was well tolerated, with mild and manageable toxicity. This is a well tolerated
      outpatient treatment regimen for patients with hormone-refractory prostatic
      cancer which deserves further investigation.

PMID- 1371565
TI  - Prostate specific antigen levels after radical prostatectomy in patients with
      organ confined and locally extensive prostate cancer.
AB  - A total of 230 patients with localized prostate cancer underwent radical
      retropubic prostatectomy at UCLA (pathological stage T1-3 N0, M0). Classification
      into groups included 115 patients with organ confined disease (group 1), 82 with
      invasion into or through the capsule (group 2) and 33 with seminal vesicle
      involvement (group 3). Median followup was 48 months. The 10-year, cause-specific
      survival was 96%, 90% and 63%, and 5-year, clinical, disease-free survival was
      91%, 79% and 58% for the 3 groups, respectively. Recent prostate specific antigen
      (PSA) levels were measured in most patients, even those operated upon many years
      ago. Of the patients 41 had detectable (0.4 ng./ml. or greater) PSA levels
      without any other clinical evidence of progression and 15 with clinical evidence
      of progression had PSA levels in the detectable range at the time of clinical
      progression. When isolated detectable PSA was also considered an indicator of
      progression the 5-year and 10-year, disease-free rates were 61% and 41%,
      respectively. These data show that radical prostatectomy performed in patients
      with even microscopic invasion into the capsule, positive margins and seminal
      vesicle involvement is associated with a higher clinical progression rate than
      organ confined disease. If isolated detectable PSA is also considered an
      indicator of recurrence the disease-free survival after radical prostatectomy
      might be less than indicated by previous studies. The relationship among
      survival, local tumor extension and PSA must be carefully examined.

PMID- 1371566
TI  - Urinary prostate specific antigen levels: role in monitoring the response of
      prostate cancer to therapy.
AB  - We have shown that prostate specific antigen (PSA) levels can be as readily
      obtained from voided urine as from serum samples. This procedure was found to
      give stable and reproducible results. PSA analyses were performed on voided urine
      collected from 42 patients with benign prostatic hypertrophy (BPH), 27 with stage
      D2 prostate cancer and 57 after radical prostatectomy. The 42 BPH samples had a
      mean urinary PSA level of 216 ng./ml., which did not correlate with estimated
      prostate size. For 4 of 5 patients with stage D2 disease who presented before
      hormonal therapy urinary PSA levels were greater than 50 ng./ml. For 22 stage D2
      patients seen after initiation of hormonal therapy the majority had low urinary
      PSA levels. After initiation of hormonal therapy in most cases low urinary PSA
      levels were found in conjunction with high serum PSA values. However, in other
      cases we found high urinary PSA with low serum PSA levels. Of 43 patients who
      underwent radical prostatectomy for stages A to C disease it was noteworthy that
      77% had elevated urinary PSA levels, while only 33% had elevated serum levels.
      Therefore, close to 80% of these patients have prostate tissue remaining locally
      after this operation.

PMID- 1371567
TI  - Detection of local recurrence after radical prostatectomy by prostate specific
      antigen and transrectal ultrasound.
AB  - Twenty patients with detectable levels of prostate specific antigen (PSA) after
      radical prostatectomy with no identifiable distant metastases were evaluated for
      local recurrence by digital rectal examination and transrectal ultrasound
      combined with biopsies. Of the patients 9 (45%) were found to have histological
      evidence of local recurrence at the initial assessment. All 4 patients with an
      abnormal digital rectal examination had recurrent disease. Transrectal ultrasound
      displayed abnormalities in 12 of the 20 patients, 7 of whom had positive
      biopsies. Random biopsies of the vesicourethral junction were performed in 8
      patients who had negative ultrasound findings and an unremarkable digital rectal
      examination, of whom 2 had histological documentation of local recurrence.
      Complications occurred in 1 patient (5%) who presented with clot retention. We
      conclude that PSA is an excellent tool for identification of recurrent disease
      after radical prostatectomy, and transrectal ultrasound guided biopsy is a useful
      diagnostic approach in patients suspected of local failure, especially when the
      digital rectal examination is unremarkable.

PMID- 1371568
TI  - The clinical usefulness of serum prostate specific antigen after hormonal therapy
      of metastatic prostate cancer.
AB  - We longitudinally followed serum prostate specific antigen (PSA) levels in 48
      patients who were treated with either orchiectomy, monthly luteinizing hormone
      releasing hormone injection or continuous diethylstilbestrol for stage D2
      prostate adenocarcinoma and achieved an objective response. Of the patients 34
      had clinical evidence of disease progression (median remission duration 19
      months). Median length of followup for the 14 patients who remained in remission
      was 42 months. Pretreatment performance status, pretreatment extent of metastases
      as measured by a bone scan and post-treatment nadir PSA level were univariately
      correlated with remission duration. After adjustment for the 2 former
      pretreatment variables, a highly significant independent effect of the nadir PSA
      level on remission duration persisted. Patients whose post-treatment nadir PSA
      level decreased below 4 ng./ml. had a significantly longer remission duration
      than those whose nadir PSA remained elevated (median 42 versus 10 months, p less
      than 0.0001). No cases were observed to progress (as defined by our criteria
      independent of PSA level) while the serial post-treatment PSA levels continued to
      decrease or remained at a plateau after reaching the nadir. The time at which the
      PSA began to increase once the nadir was reached predated objective evidence of
      progression in all patients except 2 in whom the 2 events occurred simultaneously
      (mean lead time 7.3 +/- 5.0 months). We conclude that following serial PSA levels
      in patients treated with androgen ablation for metastatic prostate cancer can aid
      in distinguishing favorable from nonfavorable responders early in the course of
      therapy and greatly assist in monitoring for progression.

PMID- 1371569
TI  - Predicting and monitoring results of therapy.

PMID- 1371570
TI  - Cholera in the Americas. Guidelines for the clinician.

PMID- 1371571
TI  - Beneficial antiarrhythmic effect of beta-blockade in patients with dilated
      cardiomyopathy.
AB  - Antiarrhythmic effects of beta-blockade (BB) in patients with dilated
      cardiomyopathy were compared with those of various antiarrhythmic agents using
      ambulatory Holter monitoring. The BB therapy effectively suppressed ventricular
      extrasystoles (VEs) in 85% of patients, as evidenced by improvement in Lown's
      grade or a reduction in the number of the highest grade VEs greater than 50%. In
      contrast, conventional antiarrhythmic agents, except flecainaid and amiodarone,
      were poorly effective in suppressing VEs. BB therapy gradually increased left
      ventricular fractional shortening (16 +/- 6% to 22 +/- 12%) and improved 12-month
      survival rates as compared with those receiving conventional therapy (93 vs 69%).
      This antiarrhythmic potency seemed to be an additional therapeutic efficacy of BB
      in the management of patients with dilated cardiomyopathy, which frequently
      associated with serious VEs.

PMID- 1371572
TI  - Endothelial leukocyte adhesion molecule-1-dependent adhesion of colon carcinoma
      cells to vascular endothelium is inhibited by an antibody to Lewis fucosylated
      type I carbohydrate chain.
AB  - Endothelial leukocyte adhesion molecule-1 (ELAM-1) has been determined to be the
      mediator of adhesion of colon carcinoma cells to interleukin-1 (IL-1)-activated
      endothelial cells. To identify ELAM-1 ligand in colon carcinoma cells, we have
      screened a series of 11 monoclonal antibodies directed to these cells and found
      that only one MBr8 was able to inhibit the IL-1-induced increment in adhesion of
      HT29 and of SW948 colon carcinoma lines to endothelial cells. In contrast, MBr8
      did not bind to polymorphonuclear cells, monocytes, and lymphocytes and did not
      inhibit polymorphonuclear adhesion to IL-1-activated endothelial cells. As
      expected, an ELAM-1 monoclonal antibody strongly inhibited IL-1 induced increment
      of adhesion of HT29, SW948, and polymorphonuclear cells. As negative control,
      MG63 osteosarcoma cells were used. These cells adhere more efficiently to IL-1
      activated endothelial cells but MBr8 and ELAM-1 monoclonal antibodies did not
      affect their adhesion. The effect of MBr8 was also tested in an experimental
      system in vivo. As described previously, radiolabeled HT29 cell retention in the
      lung of nude mice was increased in animals given IL-1. MBr8 administration to
      nude mice or pretreatment of tumor cells with it inhibited this effect. These
      data suggest that cell adhesion to ELAM-1 might be mediated by different, cell
      type specific, sugar ligands.

PMID- 1371573
TI  - [Pregnant women participating in screening must be helped with anxiety generated
      by alarming information].

PMID- 1371574
TI  - Prostate-specific-antigen-con A binding ratio in benign prostate hyperplasia and
      prostate cancer.

PMID- 1371575
TI  - Effect of FK506 on insulin secretion in normal dogs.
AB  - In this report, we describe the effect of FK506 on glucose-mediated insulin
      release in normal dogs. Dogs were placed into one of two groups, group 1 dogs
      received FK506 (1 mg/kg/d orally) for 2 weeks, and group 2 dogs received FK506 at
      the same dose, but for 4 weeks. Following the treatment period, both groups of
      dogs were allowed a recovery period during which time no FK506 was administered.
      Intravenous glucose tolerance tests (IVGTT) were performed (0.5 mg/kg IV) before
      FK506 treatment, after 2 or 4 weeks of treatment, and following the recovery
      periods. Complete blood cell counts (CBC) and serum chemistries were also
      obtained at these times. Following FK506 treatment for either 2 or 4 weeks, the
      dogs experienced a delay in glucose disappearance in response to IV glucose
      injection. Insulin secretion during IVGTT was unchanged in dogs treated for only
      2 weeks, but was significantly decreased in dogs treated for 4 weeks. Following
      the recovery period, glucose disappearance during IVGTT returned to normal in
      dogs that were treated for 2 weeks, and was more rapid than normal in dogs that
      had been treated for 4 weeks. Insulin secretion after the recovery period
      remained unchanged in group 1 dogs, but continued to be significantly reduced in
      group 2 dogs that had received FK506 for 4 weeks. No significant change was
      detected in the CBCs or serum chemistries.

PMID- 1371576
TI  - Interactions of galanin and arginine on growth hormone, prolactin, and insulin
      secretion in man.
AB  - Galanin (GAL), a 29 amino acid neuropeptide, is known to increase both basal and
      growth hormone-releasing hormone (GHRH)-induced growth hormone (GH) secretion
      while not significantly increasing prolactin (PRL) secretion in man. GAL is also
      endowed with an inhibiting effect on glucose-stimulated insulin release in
      animals, but not in man. We studied the effect of GAL (80 pmol/kg/min infused
      over 60 minutes) on the arginine- (ARG, 30 g infused over 30 minutes) stimulated
      GH, PRL, insulin, and C-peptide secretion in eight healthy volunteers (age, 20 to
      30 years). GAL induced an increase of GH (GAL v saline, area under curve [AUC],
      mean +/- SEM: 316.5 +/- 73.9 v 93.2 +/- 20.9 micrograms/L/h, P less than .05),
      but failed to modify both PRL and insulin secretion. GAL enhanced the ARG-induced
      stimulation of both GH (1,634.1 +/- 293.1 v 566.9 +/- 144.0 micrograms/L/h, P
      less than .02) and PRL secretion (1,541.9 +/- 248.8 v 1,023.8 +/- 158.7
      micrograms/L/h, P less than .02). On the contrary, GAL blunted the ARG-stimulated
      insulin (816.3 +/- 87.7 v 1,322.7 +/- 240.9 mU/L/h, P less than .05), as well as
      C-peptide secretion (105.1 +/- 9.8 v 132.8 +/- 17.3 micrograms/L/h, P less than
      .02). ARG administration induced a transient increase of glucose levels (P less
      than .01 v baseline) followed by a significant decrease (P less than .05 v
      baseline). This latter effect was prevented by the coadministration of GAL. In
      conclusion, these results show that in man GAL potentiates the GH response to
      ARG, suggesting that these drugs act at the hypothalamic level, at least in part,
      via different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371578
TI  - Structure and expression of AtS1, an Arabidopsis thaliana gene homologous to the
      S-locus related genes of Brassica.
AB  - Genetic and molecular analysis of the self-incompatibility locus (S-locus) of the
      crucifer Brassica has led to the characterization of a multigene family involved
      in pollen-stigma interactions. While the crucifer Arabidopsis thaliana does not
      have a self-incompatibility system, S-related sequence were detected in this
      species by cross-hybridization with Brassica DNA probes. In this paper, we show
      that an A. thaliana S-related sequence, designated AtS1, is expressed
      specifically in flower buds. Sequence analysis suggests that AtS1 encodes a
      secreted glycoprotein that is most similar to the Brassica S-locus related
      protein SLR1. As has been proposed for SLR1, this gene may be involved in
      determining some fundamental aspect of pollen-stigma interactions during
      pollination. The molecular and genetic advantages of the Arabidopsis system will
      provide many avenues for testing this hypothesis.

PMID- 1371577
TI  - Drosophila melanogaster paramyosin: developmental pattern, mapping and properties
      deduced from its complete coding sequence.
AB  - Several cDNA clones encoding the complete Drosophila paramyosin sequence,
      including two potential polyadenylation sites, have been obtained. Southern
      analysis and in situ hybridization to polytene chromosomes indicate that in
      Drosophila the paramyosin gene is single copy, located on the left arm of the
      third chromosome at region 66D14. Northern analyses show predominantly two
      different RNAs which are the products of the choice between the two alternative
      polyadenylation sites. The two species begin to be synthesized around 10 h of
      development when embryonic muscles are formed, expression peaking at the end of
      embryogenesis. The protein is first expressed at germ band shortening in
      association with muscle precursor cells. A second maximum of paramyosin RNA
      expression occurs at late pupal stages when the higher molecular weight form
      becomes more abundant. In young adults this species becomes the main transcript
      detected. The 102 kDa polypeptide sequence is highly similar to that of
      Caenorhabditis elegans paramyosin. The protein has a central alpha-helical coiled
      coil rod, organized in 29 groups of four typical seven-residue repeats and
      flanked by two short non-alpha-helical regions. Several leucine zippers are
      located on the hydrophobic face of the alpha-helix in paramyosin which, together
      with disulfide bonds between cysteines, are probably involved in the
      stabilization of the dimer. The structural and functional properties of
      Drosophila paramyosin deduced from the sequence are compared with those of known
      invertebrate myosins and paramyosins.

PMID- 1371579
TI  - Accumulation of chloroplast psbB RNA requires a nuclear factor in Chlamydomonas
      reinhardtii.
AB  - We have isolated and characterized a nuclear mutant, 222E, in Chlamydomonas
      reinhardtii, which is defective in photosystem II (PSII). Polypeptide P5, the
      product of psbB, is not produced in this mutant, leading to a destabilization of
      other PSII components. The mutant specifically fails to accumulate psbB
      transcripts and displays an altered transcription pattern downstream of psbB.
      Pulse-labelling experiments suggest that mRNA stability and/or processing are
      affected by the alteration of a nuclear gene product in this mutant. We show that
      the C. reinhardtii psbB gene is co-transcribed with a small open reading frame
      that is highly conserved in location and amino acid sequence in land plants. The
      5' and 3' termini of the psbB transcript have been mapped to 35 bases upstream of
      the initiation codon and approximately 600 bases downstream of the stop codon.
      The 3' flanking region contains two potential stem-loops, of which the larger
      (with an estimated free energy of -46 kcal) is near the 3' terminus of the
      transcript.

PMID- 1371580
TI  - A comparison of leaf thionin sequences of barley cultivars and wild barley
      species.
AB  - Leaf thionins of several barley cultivars and wild barley species were analysed.
      We found large differences in the numbers of leaf thionin genes in different
      Hordeum species. While, for instance, cultivars of Hordeum vulgare (Section
      Hordeum) contain more than 50 copies of thionin genes per haploid genome, the
      numbers are much lower in Hordeum species belonging to the sections Critesion and
      Stenostachys. The apparent number of genes correlates with the concentration of
      leaf thionin and its mRNA, which differs more than 100-fold among various Hordeum
      species. Leaf thionins are synthesized as high molecular weight precursor
      proteins that contain a signal peptide domain, a thionin domain and an acidic
      polypeptide domain. Analysis of cDNA clones of leaf thionins revealed a family of
      related transcripts. When the predicted amino acid sequences of the precursor
      molecules of wild barley species were compared, differences in the sequence
      variability of the three domains became apparent. The frequency of amino acid
      exchanges is much higher within the thionin domain than in the signal peptide and
      acidic polypeptide domains. The amino acid exchanges within the thionin domain do
      not occur at random but are confined to variable regions that alternate with
      highly conserved areas. Conserved regions comprise mostly cysteine residues and
      adjacent amino acids and may be important for the correct formation of the
      specific disulphide configuration of thionins.

PMID- 1371581
TI  - Chloride transport blockers prevent N-methyl-D-aspartate receptor-channel complex
      activation.
AB  - In cultured spinal cord neurons, we found that blockers of chloride transport
      (furosemide, a widely used loop diuretic, and the related compounds piretanide
      and bumetanide, as well as niflumic and flufenamic acids, used as antiinflamatory
      agents) prevented N-methyl-D-aspartate (NMDA) receptor activation in a dose
      dependent manner and are specific for this class of glutamate receptor.
      Antagonism of NMDA-mediated currents by chloride transport blockers was voltage
      independent and showed fast on-ff kinetics. The action was noncompetitive with
      NMDA and did not arise from interaction with the Zn2+ inhibitory site, because
      blockade of NMDA-induced responses by furosemide and Zn2+ was additive. The
      inhibition was greater in a low concentration of glycine, but it could not be
      overcome by increasing the glycine concentration (up to 100 microM). In contrast,
      the inhibition was attenuated by the polyamine spermine. Because the presence of
      spermine was not required for inhibition to develop, we conclude that chloride
      transport blockers are noncompetitive antagonists of the NMDA receptor, likely
      acting as inverse agonists of the polyamine site. This action may explain the
      protective effect that has been shown for some of these drugs in neuronal
      degeneration; because they also prevent neuronal swelling, they may be good
      starting compounds for synthesis of appropriate therapeutic agents to ameliorate
      excitotoxicity.

PMID- 1371582
TI  - Phosphorothioate oligonucleotides are inhibitors of human DNA polymerases and
      RNase H: implications for antisense technology.
AB  - Phosphorothioate oligodeoxycytidine (S-dCn) was used as a model compound to
      examine the impact of the number of phosphorothioate linkages and their position
      on the inhibition of human DNA polymerases and RNase H in vitro. S-dCn with a
      chain length longer than 15 could inhibit human DNA polymerases and RNase H
      activities, in a linkage number-dependent manner. Longer oligomers were more
      potent inhibitors than shorter ones. Kinetic studies indicated that S-dC28 was a
      competitive inhibitor of DNA polymerase alpha and beta with respect to the DNA
      template, whereas it was a noncompetitive inhibitor of polymerases gamma and
      delta. S-dC28 was also a competitive inhibitor of RNase H1 and H2 with respect to
      RNA-DNA duplex. Susceptibility of these enzymes to inhibition by S-dC28 was in
      the order of delta approximately gamma greater than alpha greater than beta and
      RNase H1 greater than RNase H2. Structural-activity relationships were explored
      with a group of S-dC28 analogs that have phosphorothioate internucleotide
      linkages at various positions. The inhibitory effect depended on the total number
      of thioate linkages, rather than the position of the linkages within the oligomer
      or the chain length itself. No sequence specificity was found. In the presence of
      the complementary RNA, antisense phosphorothioates (S-oligos) exerted a biphasic
      effect on RNase H activity. At low concentrations S-oligos could enhance the
      cleavage of the RNA portion of S-oligo-RNA duplex, whereas at high concentrations
      (in excess of the complementary RNA) S-oligos could inhibit RNase H and protect
      the complementary RNA from degradation. Together, these results suggest that the
      non-sequence-specific inhibitory effect of S-oligos should be taken into
      consideration in designing antisense inhibitors. This inhibitory activity could
      be avoided by decreasing the number of phosphorothioate linkages at the backbone,
      and S-oligos of 15-20 residues are preferable in antisense molecule design.

PMID- 1371584
TI  - Sex chromosome loss induced by X-rays in sperm of Drosophila.

PMID- 1371583
TI  - Quinoxaline derivatives: structure-activity relationships and physiological
      implications of inhibition of N-methyl-D-aspartate and non-N-methyl-D-aspartate
      receptor-mediated currents and synaptic potentials.
AB  - The inhibitory potencies at excitatory amino acid (EAA) receptors of 11
      quinoxaline derivatives were evaluated in two-electrode voltage-clamp recordings
      of Xenopus oocytes injected with rat cortex mRNA. Currents activated by kainate
      or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) in
      Xenopus oocytes were inhibited competitively by all the quinoxaline derivatives,
      with apparent Ki values ranging from 0.27 to 300 microM against kainate and from
      0.25 to 137 microM against AMPA. An excellent correlation was observed between
      inhibitory potencies of the quinoxaline derivatives against kainate and AMPA
      currents, in support of the contention that in this preparation these two
      agonists act at a single site. All 11 quinoxaline derivatives also inhibited
      current activated by the combination of glycine and N-methyl-D-aspartate (NMDA),
      apparently acting at the glycine site, and did so over a narrower range of
      apparent Ki values (0.37-8.1 microM). The correlation between the quinoxalines'
      kainate/AMPA potencies and their glycine/NMDA potencies was relatively weak.
      Thus, the quinoxaline derivatives were all good antagonists of glycine/NMDA
      currents and displayed a greater range of potencies against kainate and AMPA. The
      inhibitory effects of the six quinoxaline derivatives most potent in the Xenopus
      oocyte experiments were also tested against the excitatory postsynaptic field
      potential (EPSFP) recorded in the pyramidal cell dendritic field of the CA1
      region of hippocampal slices after stimulation of the Schaffer collateral
      commissural pathways. In slices superfused with "normal" medium (containing 1 mM
      Mg2+), in which the EPSFP is mediated primarily by non-NMDA receptors, IC50
      values correlated closely with the Ki values against kainate/AMPA obtained in
      oocyte experiments but were approximately 8-fold higher. Similarly, in slices
      superfused with nominally Mg(2+)-free medium, in which the EPSFP is amplified due
      to a relief of the Mg2+ block of NMDA receptors, IC50 values correlated closely
      with the Ki values against glycine/NMDA obtained in oocyte experiments but were
      60-fold higher. This comparison of results from the two experimental systems
      lends further support to the argument that hippocampal synaptic transmission is
      mediated postsynaptically by kainate/AMPA-type and NMDA/glycine-type EAA
      receptors that are pharmacologically indistinguishable from those expressed in
      mRNA-injected Xenopus oocytes. Furthermore, it suggests that EAA receptors in
      situ may be nearly saturated by high local concentrations of the endogenous
      ligands, a condition that would contribute substantially to the apparent non-NMDA
      receptor selectivity of certain quinoxaline derivatives.

PMID- 1371585
TI  - Detection of benzo[a]pyrene-diol-epoxide-DNA adducts in white blood cells of
      psoriatic patients treated with coal tar.
AB  - An enzyme-linked immunosorbent assay (ELISA) was used to detect BPDE-DNA adducts
      in white blood cells of 23 psoriatic patients undergoing clinical coal tar
      therapy. Ten of these patients were reanalyzed 2-5 months after the end of the
      coal tar treatments. The results show that the mean adduct level during the
      treatment period was 0.26 +/- 0.16 fmole BPDE/micrograms DNA (7.7 +/- 4.9
      adducts/10(8) nucleotides), while 2-5 months later the mean adduct level had
      decreased significantly (P less than 0.005) to 0.11 +/- 0.08 fmole
      BPDE/micrograms DNA (3.3 +/- 2.4 adducts/10(8) nucleotides). No relationship
      could be ascertained between the level of exposure and the amount of BPDE-DNA
      adducts. In addition, no difference in the level of DNA adducts was found between
      smoking and non-smoking patients.

PMID- 1371586
TI  - Detection by fluorescence analysis of DNA unwinding and unscheduled DNA
      synthesis, of DNA damage and repair induced in vitro by direct-acting mutagens on
      human lymphocytes.
AB  - The sensitivity and reliability of UDS and FADU in detecting mutagenic effects
      were compared by measuring DNA damage and repair in PBL treated in vitro with UV
      light, MMS and BPDE. The results indicate that FADU is more sensitive than UDS,
      as it is able to detect DNA damage at doses 3-4-fold lower. We also determined
      the DNA damage and repair induced by the above agents on lymphocyte samples from
      different donors by FADU and UDS, confirming that the DNA repair process in
      humans is characterized by interindividually variable efficiency.

PMID- 1371587
TI  - Unscheduled DNA synthesis induced by the antitumor drug vincristine in germ cells
      of male mice.
AB  - The cytotoxic and genotoxic effects of vincristine (VCR) on germ cells of male
      mice were investigated. Several parameters (the scale and the time course of
      unscheduled and scheduled DNA synthesis in spermatocytes and spermatids and the
      number of sperm present in caudal epididymides) were analyzed. Our results show
      that intraperitoneal administration of a single dose of VCR resulted in: (1)
      damage to DNA in spermatocytes and spermatids; (2) a reduction in the rate of
      germ-cell development; and (3) killing of the non-proliferating spermatid cells.
      Damage of DNA in germ cells indicates that VCR may have potential genetic hazards
      to patients who receive it in antitumor therapy.

PMID- 1371588
TI  - Micronucleus induction in bone-marrow cells following consumption of cooked beef
      in mice. Preliminary investigations.
AB  - The bone-marrow micronucleus assay was used to investigate whether the
      consumption of cooked meat could induce chromosome damage. There was no
      difference in the micronucleus frequency of mice on normal diet (cereal-based,
      non-purified diet) and mice on normal diet supplemented with microwaved meat.
      However, supplementing the normal diet with well-done pan-fried meat or rare
      charcoal-barbecued meat or well-done charcoal-barbecued meat produced significant
      increments in the micronucleus frequency of polychromatic erythrocytes--the
      increments were of the order of 73% (p = 0.045), 90% (p = 0.047) and 136% (p =
      0.001) respectively and they were observed after a 21-day feeding trial. These
      results suggest that ingestion of well-done pan-fried or barbecued meat may
      increase genetic damage, however, the accompanying decreased intake of vegetable
      constituents may have also contributed to the observed changes.

PMID- 1371590
TI  - The detection of promutagen activation by extracts of cells expressing cytochrome
      P450IA2 cDNA: preincubation dramatically increases revertant yield in the Ames
      test.
AB  - Two slightly different protocols, the plate incorporation method and the
      preincubation method, are used in the Ames Salmonella mutagen test. Using a
      preincubation method, we recently demonstrated efficient activation of a number
      of food-derived promutagens by extracts of mammalian cells expressing cDNAs of
      rat-liver cytochrome P450IA2 and of a P450IA2-IA1 hybrid. We report here that,
      for 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 1-aminoanthracene and
      several other promutagens, preincubation dramatically increased the number of
      revertant colonies in the Ames test when extracts of cytochrome P450IA2
      containing transfected cells or low concentrations of rat-liver extracts were
      used as the source of activating enzymes. At higher concentrations of rat-liver
      extract protein, the effect of preincubation was less pronounced. The effect of
      preincubation was not due to the low protein concentrations in the assays since
      increasing the total protein concentration did not abolish the requirement for
      preincubation for the detection of MeIQ activation at low concentrations of rat
      liver extract. In experiments where P450IA2 synthesized in transfected cells in
      culture is used to study promutagen activation, the plate incorporation protocol
      may seriously underestimate the capacity of cell extracts to activate
      promutagens. Thus, interlaboratory comparisons become difficult and unnecessarily
      large quantities of cell extract protein may be needed to detect promutagen
      activation. Whenever Ames test assays are carried out under conditions where P450
      concentration limits revertant yield, it would be prudent to examine both the
      preincubation and plate incorporation protocol.

PMID- 1371591
TI  - Plant extracts induce chromosome aberrations and sister-chromatid exchanges in
      Chinese hamster ovary cells and human lymphocytes.
AB  - Effects of extracts from Vicia faba were compared with those of Zea mays for the
      induction of sister-chromatid exchanges (SCEs) and of chromosome aberrations
      (CAs) in Chinese hamster ovary (CHO) cells. CA induction by the maize extract was
      also tested in human lymphocytes. The extracts from roots and leaves of Vicia
      faba induced CAs and SCEs in CHO cells. The extracts from maize leaves also
      induced SCEs and CAs in CHO cells, and CAs in human lymphocytes. Maize extracts
      were more potent in inducing SCEs than Vicia extracts and the SCE- and CA
      inducing capacity of maize extracts decreased during preincubation before
      addition to cells.

PMID- 1371589
TI  - Cytogenetic study of persons occupationally exposed to ethylene oxide.
AB  - Ten persons occupationally exposed to ethylene oxide (EO), used in the
      sterilization of medical instruments, were studied at a hospital. The estimated
      concentration to which they were exposed was 60-69 ppm, TWA. Peripheral blood
      samples from 10 workers and 10 controls of the same age and sex were taken to
      determine the frequency of sister-chromatid exchanges (SCE) and chromosomal
      aberrations (CA). The mean frequencies of SCE/cell (X = S) were 13.27 for the
      exposed workers and 6.05 for controls. Chromosome aberration frequencies in
      exposed individuals were significantly increased compared with controls. A
      significant relationship between the frequencies of SCE and CA and EO exposure
      was demonstrated. Blood chemistry parameters such as urea, creatinine, uric acid,
      lactic dehydrogenase, glutamic oxaloacetic and pyruvic transaminases, luteinizing
      gonadotropin and follicle stimulating gonadotropin and thyrotropin were also
      measured and found to be within the normal range.

PMID- 1371592
TI  - Genotoxicity and cell proliferative activity of a nitrosated Oroxylum indicum
      Vent fraction in the pyloric mucosa of rat stomach.
AB  - In vivo genotoxic activity and cell proliferative activity were examined in the
      stomach mucosa of male F344 rats by in vivo short-term methods after oral
      administration of a nitrosated Oroxylum indicum Vent (OiV) fraction, which had
      been found to be mutagenic without S9 mix to Salmonella typhimurium TA98 and
      TA100. Administration of the nitrosated OiV fraction at doses of 1 and 2 g/kg
      body weight induced dose-dependent DNA single-strand scission (p less than 0.02),
      determined by the alkaline elution method, in the stomach pyloric mucosa 2 h
      after its administration: a dose of 2 g/kg body weight induced an 18-fold
      increase in the DNA elution rate constant. Administration of the nitrosated OiV
      fraction at doses of 0.7-2.8 g/kg body weight also induced dose-dependent
      increases, up to 11-fold (p less than 0.05), in replicative DNA synthesis in the
      stomach pyloric mucosa 16 h after its administration. Moreover administration of
      the nitrosated OiV fraction at doses of 0.25-2.0 g/kg body weight induced dose
      dependent increases, up to 100-fold, in ornithine decarboxylase activity in the
      stomach pyloric mucosa with a maximum 4 h after its administration. These results
      demonstrate that the nitrosated OiV fraction has genotoxic and cell proliferative
      activity in the pyloric mucosa of rat stomach in vivo.

PMID- 1371593
TI  - Inducible stable DNA replication in Escherichia coli uvr+ and uvr- cells, treated
      with genotoxic chemicals.
AB  - Inducible stable DNA replication (iSDR) provoked by a damaging treatment with
      MMS, MNU, MNNG, NFAA, NFN, 4NQO, NAL or MMC, was followed in both repair
      competent E. coli PQ35 and its uvrA derivative E. coli PQ37. In contrast to SOS
      inducible mutagenesis, which is more pronounced in excision-deficient cells, iSDR
      was more obvious in repair-competent cells. This may be due to special features
      of iSDR and need not indicate involvement of the uvrA gene product in it.

PMID- 1371594
TI  - Bioassay-directed fractionation of mutagenic PAH atmospheric photooxidation
      products and ambient particulate extracts.
AB  - Simulated atmospheric gas-phase reactions of naphthalene, fluorene and
      phenanthrene have been carried out in an environmental chamber with bioassay
      directed chemical analysis of the reaction products. Nitro-PAH were found to be
      the most significant mutagens formed from the reactions of naphthalene and
      fluorene. The mutagram (bar graph of mutagenic activity versus HPLC fraction) of
      the phenanthrene reaction products closely resembled that of an ambient air
      particulate extract with the most mutagenic activity being in a fraction more
      polar than that in which the nitro-PAH elute. Nitrophenanthrene lactones (nitro
      6H-dibenzo[b,d]pyran-6-ones) were found to account for the observed activity of
      this polar fraction of the phenanthrene reaction products. It has been shown that
      the utilization of an environmental chamber with a known PAH-starting material
      and the ability to produce sufficient product for isomer-specific identifications
      of mutagens is a promising complement to bioassay-directed fractionation of
      ambient air particulate extracts.

PMID- 1371595
TI  - Wonky mice and MBP promoter.

PMID- 1371596
TI  - Protein engineering in haemoglobin.

PMID- 1371597
TI  - Dystrophin mRNA in lyophilized tissue.

PMID- 1371598
TI  - Volume-regulated chloride channels associated with the human multidrug-resistance
      P-glycoprotein.
AB  - Expression of P-glycoprotein, the product of the MDR1 gene, confers multidrug
      resistance on cell lines and human tumours (reviewed in refs 1,2). P-glycoprotein
      (relative molecular mass 170,000) is an ATP-dependent, active transporter which
      pumps hydrophobic drugs out of cells, but its normal physiological role is
      unknown. It is a member of the ABC (ATP-binding cassette) superfamily of
      transporters, which includes many bacterial transport systems, the putative
      peptide transporter from the major histocompatibility locus, and the product of
      the cystic fibrosis gene (the cystic fibrosis transmembrane regulator, CFTR).
      CFTR is located in the apical membranes of many secretory epithelia and is
      associated with a cyclic AMP-regulated chloride channel. At least two other
      chloride channels are present in epithelial cells, regulated by cell volume and
      by intracellular Ca2+, respectively. Because of the structural and sequence
      similarities between P-glycoprotein and CFTR, and because P-glycoprotein is
      abundant in many secretory epithelia, we examined whether P-glycoprotein might be
      associated with one or other of these channels. We report here that expression of
      P-glycoprotein generates volume-regulated, ATP-dependent, chloride-selective
      channels, with properties similar to channels characterized previously in
      epithelial cells.

PMID- 1371599
TI  - The cocaine-insensitive component of non-exocytotic efflux of noradrenaline from
      adrenergic axons in the isolated rat tail artery.
AB  - The working hypothesis was that the cocaine-insensitive component of non
      exocytotic efflux of noradrenaline represents diffusion of the unprotonated amine
      across the axonal membrane. It was tested by examination of the effect of
      changing axoplasmic pH--and thus the fraction of extravesicular noradrenaline in
      the unprotonated form--on the overflows of endogenous noradrenaline and 3,4
      dihydroxyphenylethylene glycol from rat tail arteries. The catechols were assayed
      by liquid chromatography with amperometric detection. To dissipate the H+
      gradient across the axonal membrane, the tissues were incubated in media of
      different pH, in which Na+ was completely replaced with K+ and which were HCO3(-)
      (and Ca(2+)-)free. Exposure of the tissues to these media produced substantial,
      but reversible increases in the overflow of noradrenaline. Subsequently, the
      overflows of both noradrenaline and the glycol kept rising, but their ratio did
      not change. Cocaine (0.1 mmol/l) lowered the (noradrenaline overflow: glycol
      overflow) ratio significantly. The ratio observed in its presence increased
      steeply with decreasing external and, presumably, axoplasmic pH. Addition of
      valinomycin and carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (1 mumol/l
      each) to the cocaine-containing media more than doubled the overflows without
      altering significantly the ratio. Under identical conditions, the overflow of
      noradrenaline from preparations with inactive neuronal monoamine oxidase did not
      decrease with decreasing pH. Since, in the presence of cocaine, the overflow
      ratio increased--rather than decreased--with decreasing pH, and because the
      overflow or noradrenaline from preparations with inactive monoamine oxidase did
      not decline with pH, the cocaine-insensitive component of noradrenaline efflux
      does not seem proportional to the axoplasmic concentration of the unprotonated
      amine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371600
TI  - Molecular aspects of glutamate receptors and sodium-calcium exchange carriers in
      mammalian brain: implications for neuronal development and degeneration.
AB  - N-Methyl-D-aspartate (NMDA) and L-glutamate activate membrane receptors that
      produce substantial permeation of Na+, K+ and Ca2+ through the neuronal membrane.
      These ionic fluxes are intimately linked to processes that regulate neuronal
      survival, growth and differentiation. Intracellular free Ca2+ concentrations are
      thought to be particularly important determinants of the vulnerability of neurons
      to excessive excitatory stimulation produced through activation of NMDA
      receptors. In order to understand the molecular events involved in both NMDA
      receptor activation and regulation of intracellular Ca2+ levels, we have purified
      and reconstituted the protein complexes that form the NMDA/glutamate receptors in
      rat brain synaptic membranes and those that constitute the Na(+)-Ca2+ antiporters
      in bovine brain synaptic membrane. The molecular properties of these protein
      complexes are described, and information from the most recent studies of
      exploration of the molecular structures of these receptors and transport carriers
      is summarized.

PMID- 1371602
TI  - Presynaptic modulation of amino acid release from synaptosomes.
AB  - Using synaptosomes prepared from whole rat brain, the spontaneous, calcium
      independent, and calcium-dependent release of glutamate and GABA was assessed.
      Time intervals of 1-30 seconds were studied. Spontaneous release of glutamate
      (but not GABA) was elevated by 10 microM NMDA or AMPA by thirty seconds. This
      stimulation was partially calcium-dependent. Calcium-dependent release induced by
      30 mM KCl was biphasic, confirming previous findings. This release was stimulated
      at all time periods by the presence of 10 microM NMDA or AMPA in an antagonist
      sensitive manner. These data suggest that glutamate and GABA are released from
      vesicular stores in rat synaptosomes and that some of this release is modulated
      by presynaptic glutamate receptors.

PMID- 1371601
TI  - Possible role of cGMP in excitatory amino acid induced cytotoxicity in cultured
      cerebral cortical neurons.
AB  - Using cultured cerebral cortical neurons at mature stages (9 days in culture,
      d.i.c.) it was demonstrated that glutamate, NMDA (N-methyl-D-aspartate) and to a
      lesser extent KA (kainate) increase the intracellular cGMP concentration
      ([cGMP]i) whereas no such effect was observed after exposure of the cells to QA
      (quisqualate) and AMPA (2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate).
      No effect of glutamate, NMDA and KA was observed in immature neurons (2 d.i.c.).
      The pharmacology of these cGMP responses was investigated using the glutamate
      antagonists APV (2-amino-5-phosphonovalerate) with selectivity for NMDA
      receptors, CNQX (6-cyano-7-nitro-quinoxaline-2,3-dione) with selectivity for non
      NMDA receptors and the novel KA selective antagonists AMOA (2-amino-3-[3
      (carboxymethoxy)-5-methylisoxazol-4-yl]propionate) and AMNH (2-amino-3-[2-(3
      hydroxy-5-methylisoxazol-4-yl)methyl-5-methyl-3- oxoisoxazolin-4-yl]propionate).
      In addition, the cytotoxicity of glutamate, NMDA and KA was studied and found to
      be enhanced by addition of the non-metabolizable cGMP analogue 8-Br-cGMP. On the
      contrary, the toxicity of QA and AMPA was not affected by 8-Br-cGMP. Pertussis
      toxin augmented the toxicity elicited by glutamate, NMDA, KA and QA but not that
      induced by AMPA. On the other hand, only glutamate and KA induced toxicity was
      potentiated by cholera toxin, which also enhanced the stimulatory effect of
      glutamate and NMDA but not that of KA on the cellular cGMP content. The toxicity
      as well as the effects on intracellular cGMP levels could be antagonized by the
      specific excitatory amino acid (EAA) antagonists.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1371604
TI  - [Cancer of the breast in young women: should chemotherapy be intensified?].

PMID- 1371605
TI  - [In vitro conversion of carcinoma cells into fibroblastic cells. Induction,
      mechanism of action and importance in invasion and metastasis].

PMID- 1371603
TI  - Is myelin basic protein crystallizable?
AB  - Myelin basic protein (MBP) is the predominant extrinsic protein in both central
      and peripheral nervous system myelins. It is thought to be involved in the
      stabilizing interactions between myelin membranes, and it may play an important
      role in demyelinating diseases such as multiple sclerosis. In spite of the fact
      that this abundant protein has been known for almost three decades, its three
      dimensional crystal structure has not yet been determined. In this study we
      report on our extensive attempts to crystallize the major 18.5 kDa isoform of
      MBP. We used MBP having different degrees of purity, ranging from crude MBP (that
      was acid or salt extracted from isolated myelin), to highest purity single
      isoform. We used convention strategies in our search for a suitable composition
      of a crystallization medium. We applied both full and incomplete factorial
      searches for crystallization conditions. We analyzed the available data on
      proteins which have previously resisted crystallization, and applied this
      information to our own experiments. Nevertheless, despite our efforts which
      included 4600 different conditions, we were unable to induce crystallization of
      MBP. Previous work on MBP indicates that when it is removed from its native
      environment in the myelin membrane and put in crystallization media, the protein
      adopts a random coil conformation and persists as a population of structurally
      non-identical molecules. This thermodynamically preferred state presumably
      hinders crystallization, because the most fundamental factor of protein
      crystallization - homogeneity of tertiary structure--is lacking. We conclude that
      as long as its random coil flexibility is not suppressed, 18.5 kDa MBP and
      possibly also its isoforms will remain preeminent examples of proteins that
      cannot be crystallized.

PMID- 1371606
TI  - The use of growth hematopoietic factors in AIDS.

PMID- 1371607
TI  - Zinc-induced molt: evidence for a direct inhibitory effect on granulosa cell
      steroidogenesis.
AB  - Results from previous studies indicate that the use of dietary zinc may provide
      an effective means to initiate an induced molt in laying hens. Although much
      evidence indicates that high concentrations of zinc (10,000 to 20,000 ppm) cause
      the cessation of lay primarily by depressing feed intake, recent data suggest
      that lower concentrations (2,800 ppm) in a calcium-deficient diet may act via a
      direct action on the ovary. Therefore, a series of in vitro studies was conducted
      to evaluate whether zinc can affect granulosa cell progesterone production.
      Incubation of granulosa cells from the largest preovulatory (F1) follicle with
      zinc as zinc sulfate (.1 to 10 microM) had no effect on basal progesterone
      production. By contrast, ovine luteinizing hormone-stimulated progesterone
      production was inhibited (P less than .05) in a dose-related fashion by zinc in
      both the sulfate and acetate forms (1 to 10 microM). Furthermore, zinc attenuated
      oLH- and forskolin-induced cyclic adenosine monophosphate (cAMP) formation, and
      inhibited 8-bromo-cAMP- and calcium ionophore (A23187)-induced progesterone
      production. Such results indicate both pre- and post-cAMP sites of action for
      zinc's inhibitory actions on progesterone production in F1 granulosa cells.
      Finally, ovine follicle-stimulating hormone-stimulated cAMP accumulation and
      progesterone production in granulosa cells collected from 9- to 12-mm follicles
      (a stage of development representing the early, rapid growth phase) were
      suppressed (P less than .05) by co-incubation of cells with zinc.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1371608
TI  - Continuous endotoxin infusion suppresses rat spleen cell production of cytokines.
AB  - Endotoxin, i.e., lipopolysaccharides, was continuously infused into rats at a
      nonlethal dose by means of an implanted osmotic pump for up to 2 weeks. The pump
      was connected to the jugular vein by a polyethylene catheter. Administration of
      endotoxin via the pump compromised the ability of spleen cells to produce the
      lymphokines interleukin 1 and tumor necrosis factor after stimulation in vitro
      with endotoxin. In addition, the ability of the spleen cells to produce
      alpha/beta-interferon in response to endotoxin in vitro was also examined, as was
      the capability of the spleen cells to produce gamma-interferon following
      stimulation with concanavalin A. Suppression of the expected interleukin 1 and
      tumor necrosis factor production by spleen cells from rats continuously infused
      with endotoxin was observed. There was also a moderate effect on interferon
      production, but this was much less. These results provide further findings
      indicating the unresponsiveness of spleen cells to lipopolysaccharides, as well
      as to a nonspecific plant mitogen, following continuous infusion of endotoxin
      into rats via an implanted osmotic pump. Additional studies are needed to
      determine the mechanisms involved in such suppression.

PMID- 1371609
TI  - Correlations between catecholamine levels and sexual behavior in male zebra
      finches.
AB  - In zebra finches, the combined actions of estrogens and androgens activate male
      courtship, including singing, and also strongly modulate norepinephrine (NE)
      levels and turnover in brain areas known to be involved in controlling courtship
      behavior. To determine whether changes in NE levels mediate changes in courtship,
      we administered DSP-4 to males and measured its effects on monoamine levels and
      reproductive behavior. DSP-4 treatment did not affect serotonin (5-HT), had
      small, variable effects on dopamine (DA), and caused moderate, nonsignificant
      reductions in NE. However, in DSP-4-treated males, NE levels in specific vocal
      control nuclei showed high positive correlations with courtship singing. There
      were no significant correlations between NE levels in hypothalamic nuclei and any
      behavior or DA or 5-HT levels in any nuclei and any behavior. DSP-4-treated males
      took longer to begin singing and performed fewer song bouts and courtship
      displays, but their songs could not be differentiated from those of control
      males. This suggests that their behavioral deficits resulted from deficits in
      attention rather than an inability to sing.

PMID- 1371611
TI  - The substance P fragment SP(1-7) stimulates motor behavior and nigral dopamine
      release.
AB  - Earlier studies have shown that the undecapeptide substance P (SP) alters motor
      behavior and dopamine metabolism following injection into the substantia nigra
      (SN) in rat, even though the SN appears largely devoid of SP-specific (NK-1)
      receptors. In this report, intra-nigral injections of the amino-terminal SP
      fragment SP(1-7) enhanced rearing, sniffing and locomotor activity, and increased
      the nigral DOPAC-to-DA ratio. In addition, SP(1-7) increased 3H-DA release from
      the SN in vitro. These findings suggest that some of the effects of nigral SP on
      motor behavior and dopamine release are mediated by amino-terminal fragments of
      SP.

PMID- 1371610
TI  - Effects of DM-9384, a pyrrolidone derivative, on ischemia-induced changes in the
      central monoamine systems.
AB  - Alterations in brain tissue levels of monoamines and monoamine metabolites were
      studied in gerbils 60 min after cerebral ischemia induced by 10 min carotid
      ligation after pretreatment with the antiischemic drug DM-9384 (1, 3, 10, 30
      mg/kg, PO). The DA levels decreased in striatum after the ischemia, while
      cortical and hippocampal DA levels increased. The DOPAC levels increased in
      cortex, but were essentially unaffected in other regions. The HVA levels
      increased in all forebrain regions studied. NA levels decreased in hippocampus
      and superior colliculus, while a general increase in MHPG levels was seen.
      Decreases in 5-HT levels were seen in all forebrain regions except cortex. The 10
      mg/kg and 30 mg/kg doses of DM-9384 counteracted the decrease in striatal 5-HT
      and hypothalamic MHPG/NA ratio, respectively. Thus pretreatment with DM-9384
      exerted minor protective effects on the alterations induced in monoamine systems
      by transient forebrain ischemia.

PMID- 1371612
TI  - Galanin is more common than NPY in vascular sympathetic neurons of the brush
      tailed possum.
AB  - The distribution of galanin (Gal) in sympathetic vascular neurons of adult and
      juvenile brush-tailed possums (Trichosurus vulpecula), was examined using double
      labelling immunohistochemistry. This was compared with the distribution of
      neuropeptide Y (NPY) in the same tissues. Immunoreactivity (IR) to galanin was
      present in the majority (64-99%) of nerve cell bodies in paravertebral
      sympathetic ganglia, where it mostly co-existed with IR to the catecholamine
      synthesizing enzyme, tyrosine hydroxylase (TH). Gal-IR also was present in most,
      if not all, TH-IR perivascular axons supplying systemic arteries and veins. NPY
      IR was less common than Gal-IR in all sympathetic ganglia and perivascular axons
      examined. Some sympathetic, TH-IR axons supplying the abdominal aorta and renal
      artery contained both Gal-IR and NPY-IR, while TH-IR axons supplying cephalic and
      thoracic vessels contained Gal-IR but not NPY-IR. Limited observations on
      sympathetic neurons in two species of wallabies indicated that Gal-IR also was
      more common than NPY-IR in other marsupial species, but the incidence of NPY-IR
      was higher in these wallabies than in the brush-tailed possum. Together with
      previous studies, this work suggests that the coexistence of galanin and NPY may
      be the primitive condition for sympathetic neurons in tetrapods. The differential
      expression of these peptides in specific populations of sympathetic neurons may
      have important functional consequences in the autonomic control of the
      circulation.

PMID- 1371613
TI  - Cooperative effects of bombesin, substance P and methacholine on the release of
      intestinal neurotensin in rats.
AB  - The secretion of ileal neurotensin (NT) results from events occurring at the
      apical and basal side of the N-cells. The hypothesis of a functional relationship
      between cholinergic and peptidergic neurones with the N-cell was investigated in
      the present study utilizing the isolated vascularly perfused rat ileum.
      Intraarterial methacholine (MC, 10(-4) M) evoked a prompt and well sustained
      release of NT in the portal effluent (plateau value at 500% of basal). This
      effect was dose-dependent over the range of 10(-6) M to 10(-4) M. Bombesin (B)
      provoked a dose-dependent peak secretion of NT (800% of basal at 10(-7) M)
      followed by a rapid return to almost basal levels. The B-induced NT release
      remained unaltered upon 10(-6) M tetrodotoxin (TTX) or 10(-5) M atropine
      infusion. Substance P (SP) potently stimulated the release of NT. The maximal
      response, consisting of a sustained secretion, was observed at a concentration of
      10(-7) M (350% of basal) while 10(-6) M SP induced a transient release. TTX or
      atropine did not reduce significantly the SP-induced secretion of NT. Neurokinin
      A and B did not increase NT concentrations in the portal effluent. B
      synergistically increased the secretion of NT induced by SP. Atropine or TTX did
      not modify the effect of combined SP and B infusion. MC potentiated the release
      of NT induced by B but not that evoked by SP. Combined infusion of SP, B and MC
      produced the largest output of NT. In conclusion, B, SP and MC are strong
      stimulants of NT release in rats. In addition, the cooperative effects of these
      transmitters argue in favor of a complex functional relationship between the
      intramural nervous network and the intestinal N-cells in rats.

PMID- 1371614
TI  - Biochemical basis for mouse resistance to hyaline droplet nephropathy: lack of
      relevance of the alpha 2u-globulin protein superfamily in this male rat-specific
      syndrome.
AB  - It is well-established that binding of a chemical to alpha 2u-globulin is the
      rate-limiting step in the development of male rat-specific hyaline droplet
      nephropathy. Mice synthesize mouse urinary protein (MUP), a protein which is very
      similar to alpha 2u-globulin, but this protein does not render the mouse
      sensitive to a similar renal toxicity. Therefore, the purpose of the present
      study was to determine the biochemical basis for mouse resistance to hyaline
      droplet nephropathy. Male Fischer 344 rats and B6C3F1 mice excreted 12.24 +/-
      0.60 and 14.88 +/- 0.99 mg of alpha 2u-globulin and MUP daily, indicating that
      quantitative differences in protein excretion were not involved in the species
      specificity of the nephropathy. With d-limonene as a model hyaline droplet
      inducing agent, both rat and mouse liver microsomes oxidized the terpene to its
      1,2-epoxide (the metabolite that binds reversibly to alpha 2u-globulin in vivo),
      demonstrating that metabolic differences do not determine the mouse resistance to
      this lesion. In spite of the formation of the epoxide intermediate, no binding of
      [14C]d-limonene equivalents to mouse kidney proteins was observed. In contrast,
      about 40% of the d-limonene equivalents in male rat kidney was reversibly bound
      to renal proteins. The renal reabsorption of alpha 2u-globulin and MUP was
      markedly different, as rats reabsorbed about 60% of the total filtered load of
      alpha 2u-globulin, but MUP was not reabsorbed by the mouse kidney. Given the
      absence of MUP in mouse kidney, in vitro equilibrium saturation binding studies
      were also conducted to determine whether MUP could bind the epoxide metabolite.
      alpha 2u-Globulin bound [14C]d-limonene-1,2-oxide with an apparent Kd of 4 x 10(
      7) M. However, under identical experimental conditions, MUP failed to bind the
      epoxide. These data indicate that two major biochemical differences between alpha
      2u-globulin and MUP contribute to mouse resistance to hyaline droplet
      nephropathy. Under both in vivo and in vitro conditions, MUP does not bind d
      limonene-1,2-oxide, the rate-limiting step in the development of the nephropathy.
      However, even if MUP did bind the epoxide, the fact that it is not reabsorbed
      into the mouse kidney precludes its involvement in a syndrome involving renal
      protein overload. Finally, the absence of an interaction between d-limonene, a
      model hyaline droplet inducer, and the protein most similar to alpha 2u-globulin
      suggests that no other protein in the alpha 2u-globulin superfamily is likely to
      cause hyaline droplet nephropathy in other species.

PMID- 1371615
TI  - Induction of quinone reductase and glutathione in bone marrow cells by 1,2
      dithiole-3-thione: effect on hydroquinone-induced cytotoxicity.
AB  - Stromal cells from bone marrow are susceptible to toxicity induced by several
      redox-active metabolites of benzene, including hydroquinone (HQ). We have
      previously shown that tert-butyl-hydroquinone (tBHQ) can induce quinone reductase
      (QR) in bone marrow stroma as well as protect stromal cells against HQ-induced
      toxicity. Current studies investigate the underlining mechanisms of
      chemoprotection against HQ in DBA/2- and C57Bl/6-derived bone marrow stromal
      cells. The chemoprotector 1,2-dithiole-3-thione (DTT) has been used in these
      studies due to tBHQ toxicity to stromal cells at higher concentrations.
      Pretreatment of cells with DTT prior to HQ administration protected cells against
      HQ-induced toxicity. DTT induced QR activity in a dose-dependent manner in
      stromal cells from both strains of mice. However, there were no corresponding
      changes in glutathione transferase activity. DTT also increased cytosolic
      glutathione (GSH) concentrations by approximately 85% in both strains. Since bone
      marrow stroma consists primarily of fibroblasts and macrophages, we also
      evaluated QR activity in the separate cell types from the two strains of mice.
      There were differences in basal and DTT-induced QR activity between fibroblasts
      and macrophage cells derived from the same strain of mice, as well as the
      expected differences between strains. Additionally, dicoumarol, an inhibitor of
      QR activity, potentiated HQ-induced toxicity in both strains of bone marrow
      stromal cells. Thus, cellular glutathione, QR activity, and their inducibility by
      chemoprotective agents such as DTT may prove to be important factors in
      chemically induced bone marrow toxicity and carcinogenicity.

PMID- 1371616
TI  - Pancreatic transplant rejection: evaluation by duplex-Doppler ultrasound with
      urinary amylase monitoring correlation.

PMID- 1371617
TI  - A comparison of techniques for the isolation of mature mouse islets.

PMID- 1371618
TI  - Induction of an acute phase response after OKT3 therapy.

PMID- 1371619
TI  - Hepatitis C antibody in renal transplant patients.

PMID- 1371620
TI  - The effect of ATG treatment on T-cell subpopulations in peripheral blood of
      inbred rats.

PMID- 1371621
TI  - FK 506 and cyclosporine inhibit antigen- or mitogen-induced monokine and
      lymphokine production in vitro.

PMID- 1371622
TI  - Occlusion of the pancreatic duct: a case of impaired pancreas graft function.

PMID- 1371623
TI  - Blockade of interleukin-2 production from cloned T cells by cyclosporine and FK
      506 assessed by proliferation assays in vitro.

PMID- 1371624
TI  - Enhanced liver regeneration by FK 506 can be blocked by interleukin-1 alpha and
      interleukin-2.

PMID- 1371625
TI  - Effect of renal ischemia on plasma levels of FK 506 in rats.

PMID- 1371627
TI  - Clinical implications of the presence of antibodies to hepatitis C after renal
      transplantation.

PMID- 1371628
TI  - Hepatitis C virus infection in kidney transplant patients.

PMID- 1371626
TI  - Infections during a randomized trial comparing cyclosporine to FK 506
      immunosuppression in liver transplantation.

PMID- 1371629
TI  - [Alfuzosin. A new selective alpha 1 receptor antagonist for symptomatic medical
      treatment of benign prostatic hypertrophy prior to surgery].

PMID- 1371630
TI  - [Chronic congenital neutropenia treated with granulocyte colony-stimulating
      factor (G-CSF)].
AB  - Kostmann's syndrome is a congenital disorder characterized by persistent severe
      neutropenia. It has a high morbidity and mortality on account of serious
      bacterial infection. A case which was successfully treated with G-CSF is
      reported.

PMID- 1371631
TI  - Percutaneous transrenal ureteral occlusion: indication and technique.
AB  - Several techniques for achieving palliative ureteral occlusion in cases of
      underlying malignant diseases are known to exist. We performed nine ureteral
      occlusions on seven patients, using two different techniques (occlusion by
      detachable balloon and by "Harzmann Olive"). Initially, complete occlusion of all
      ureters was attained; in two cases a second occluding intervention had to be
      carried out after a period of 6 and 14 weeks. Six of seven patients enjoyed a
      marked improvement of their quality of life after occlusion. Complications were
      down to a minimum. In comparison with other techniques described in the
      literature, Harzmann's method seems to be the simplest, as well as the most fully
      developed one. It may also be recommended for patients in an advanced tumor
      stage.

PMID- 1371632
TI  - Biophysical mechanism of the scavenger site near T cell-presented epitopes.
AB  - We seek to identify consensus sequences in digested fragments of antigenic
      proteins regulating selection and major histocompatibility complex (MHC)
      restricted presentation to T cells of epitopes within those fragments. One such
      pattern, of recurrent, hydrophobic sidechains forming a longitudinal hydrophobic
      strip when a sequence is coiled as an alpha-helix, is found in or near most T
      cell-presented epitopes. Such recurrent hydrophobicity may lead to protease
      protected coiling of the fragment against endosomal membranes and transfer to MHC
      molecules. This concept leads to better identification of T cell-presented
      sequences and possible to engineering of T cell-presented vaccines to affect
      their potency and MHC restriction.

PMID- 1371633
TI  - Diazepam and atropine as premedicants: no discrimination by monoamine metabolite
      and catecholamine measurements in cerebrospinal fluid and plasma.
AB  - The relationships between self-reported assessments of the quality of the
      preoperative night's sleep, preoperative anxiety, and several biochemical and
      physiological indicators of stress reaction were investigated in pregnant women
      at term receiving no premedication (n = 15), a placebo tablet (n = 15), diazepam
      5 mg p.o. (n = 15), or atropine 0.01 mg/kg i.m. (n = 15), in connection with
      spinal analgesia for elective caesarean section. In the patients receiving no
      premedication, the subjective estimate of the quality of the preoperative night's
      sleep was negatively associated with concentrations of noradrenaline (NA) and its
      metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG) in CSF, and with plasma
      adrenaline. The anxiolytic effect of diazepam was reflected as significantly
      lower plasma levels of another metabolite of NA, 3,4-dihydroxyphenylglycol
      (DHPG). Placebo and diazepam, and to a lesser extent atropine, confounded the
      statistical relationships between the clinical and biochemical responses found in
      the patients with no premedication. On the whole, the biochemical monoamine
      measurements were of little use in determining the clinical effects of different
      kinds of premedicants.

PMID- 1371634
TI  - Treatment of terminal cancer pain in Finland: a second look.
AB  - A questionnaire concerning the treatment of cancer pain was sent to 10% and 5%
      random samples of Finnish physicians in 1985 and in 1990, respectively. The
      physicians were asked about their current practice in the treatment of pain in
      their cancer patients, and about their main clinical problems when treating pain.
      Three simulated patient cases were presented, and the adequacy of the suggestions
      for therapy was evaluated. The results indicated that Finnish physicians had
      adopted a more rational and effective analgesic therapy during the 5-year period.
      Treatment suggestions for the simulated patient cases had improved both in terms
      of daily doses of analgesics and of dose intervals, but the doses of opioids were
      still below those commonly used in chronic cancer pain. The clinical difficulties
      experienced by the physicians had changed: instead of being frustrated by the
      inefficacy of their treatment as in 1985, physicians were now working on the
      problem of finding a suitable preparation and dosage. The results suggest that
      the voluntary activity of patient organizations, a few pain clinics, and a few
      clinicians interested in pain treatment have been able to improve the practising
      physicians' theoretical knowledge in 5 years. In contrast to the improvement in
      the knowledge and skills, changing attitudes takes much longer. As many as 39% of
      physicians who see cancer patients at least occasionally, reported that they
      still had not acquired the prescription sheets necessary to prescribe opioids to
      outpatients.

PMID- 1371635
TI  - Unexpected PR prolongation following nonconducted atrial extrasystoles: a
      manifestation of concealed reentry.

PMID- 1371636
TI  - Ventricular tachycardia in plasma cell dyscrasia syndrome.

PMID- 1371637
TI  - Comparison between the clinicopathologic features of AFP-positive and AFP
      negative gastric cancers.
AB  - We compared 27 cases of alpha-fetoprotein (AFP)-positive gastric cancer with 478
      cases of AFP-negative gastric cancer in our department. The incidences of AFP
      positive gastric cancer were 5.4% (27/505), 7.2% (23/218), and 2.1% (4/187) for
      overall, advanced, and early cases of gastric cancer, respectively. Sex, age
      distribution, pathologic type, and serum carcinoembryonic antigen levels were
      similar between these two groups. Borrmann III type cancer, lymph node
      metastasis, lymphatic and venous microinvasion of the gastric wall, and incidence
      of synchronous and metachronous liver metastasis occurred more often in the AFP
      positive group. It was suspected that the character of early venous invasion
      contributed to the high incidence of liver metastasis. Liver metastasis occurred
      in 72% of AFP-positive patients, all of whom died within 2 yr. Long-term survival
      of the AFP-positive group was worse than that of the negative group. The 1-, 3-,
      5-, and 7-yr survival rates of both groups were 38.7%, 11.6%, 11.6%, 11.6%, and
      71.3%, 57.8%, 52.8%, 49.6%, respectively (p less than 0.001).

PMID- 1371638
TI  - Hyperamylasemia in patients with the acquired immunodeficiency syndrome.
AB  - Marked elevations of serum amylase, unexplained despite extensive evaluation in
      patients with acquired immunodeficiency syndrome (AIDS), prompted this
      retrospective review of 85 patients to determine the prevalence of
      hyperamylasemia and identify any associated demographic and etiologic factors. Of
      39 patients who had amylase determinations, 54% had hyperamylasemia (2/3
      pancreatic, 1/3 salivary) and 31% had pancreatitis. Biliary tract disease,
      alcohol intake, and opportunistic infections were similar in hyperamylasemic and
      normoamylasemic subjects. Non-Caucasian race, intravenous drug abuse, renal
      dysfunction, alkaline phosphatase elevation, and pentamidine use were more
      prevalent in patients with hyperamylasemia (p less than 0.001, p less than 0.001,
      p less than 0.01, p less than 0.05, and p less than 0.05, respectively). However,
      by stepwise deletion multiple regression analysis, only non-Caucasian race,
      pentamidine use, and Mycobacterium avium-intracellulare infection were
      significant, independent predictors of hyperamylasemia (R2 = 0.65). Followed over
      time, in a historical prospective manner, case fatality rates (66.6% and 61.1%)
      and median survival times (101 and 84 days) were similar in the hyperamylasemic
      and normoamylasemic groups. We conclude that, although pancreatitis occurs
      frequently in AIDS, hyperamylasemia is often of salivary origin and clinical
      outcome is unaffected. Certain demographic factors are strongly associated with
      hyperamylasemia in AIDS patients, but multiple, concurrent, etiologic factors are
      probably operative in these patients.

PMID- 1371639
TI  - Ethanol and human saliva: effect of chronic alcoholism on flow rate, composition,
      and epidermal growth factor.
AB  - Parotid saliva samples from 24 alcoholic subjects without evidence of cirrhosis
      were analyzed for changes in flow rate, composition, and epidermal growth factor
      (EGF) secretion. Mean (+/- SE) stimulated parotid saliva flow rate (ml/min/gland)
      was significantly (p less than 0.01) lower in alcoholic subjects than in matched
      control subjects. Reduction in parotid saliva flow rate was associated with
      significant (p less than 0.05) decrease in total protein and amylase secretion in
      this group of patients. In addition, secretion of immunoreactive EGF, a specific
      salivary protein, was also markedly reduced (p less than 0.05) in alcoholic
      patients. None of the parotid saliva samples from the alcoholic subjects had
      detectable bioactivity of EGF in saliva. These data suggest that chronic alcohol
      ingestion is associated with significant changes in parotid saliva secretion and
      its composition, which may perpetuate and compound ethanol-induced injury to the
      upper gastrointestinal tract.

PMID- 1371640
TI  - Case report: distinctive immune abnormalities in a patient with procainamide
      induced lupus and serositis.
AB  - To gain insight into the immunopathogenesis of drug-induced autoimmune disorders,
      lymphocyte and immunoglobulin distributions and cytokine levels were monitored in
      the peripheral blood and pleural fluid of a patient with procainamide-induced
      lupus and pleural effusion. Approximately 80% of the B cells in both compartments
      were CD5+ compared to 10% to 25% in normal adults. CD4/CD8 ratio and percentage
      CD4 were normal in peripheral blood. Serum levels of IgG (particularly IgG2), IL
      6, and soluble IL-2R were slightly elevated, and those of IgA were significantly
      elevated compared to normal controls. Analysis of the pleural effusion revealed
      an increased CD4/CD8 ratio because of an increased percentage of CD4+CD29+ helper
      memory T cells, lack of expression of the resting B-cell marker CD21, immune
      complex deposition and complement consumption, increased relative levels of ANA,
      abnormally high levels of IL-6 and soluble IL-2R, and detectable levels of IL-1b,
      IFN-g and TNF-a. These observations provide evidence for the involvement of CD5+
      B cells and differential helper T-cell activity in procainamide-induced lupus and
      for an association between local lymphocyte activation and organ pathology.

PMID- 1371641
TI  - Antibodies against the cystic fibrosis transmembrane regulator.
AB  - Rabbit polyclonal antibodies have been raised against high-performance liquid
      chromatography purified synthetic peptides corresponding to two discrete regions
      of the cystic fibrosis transmembrane regulator (CFTR) protein: the R-domain
      (residues 785-796) and the extreme COOH-terminus (residues 1467-1480). Antibodies
      (Ab) to each of these peptides were affinity purified either by passage over a
      peptide-derivatized agarose matrix (Ab 785) to produce monospecific polyclonal
      antibodies or by protein A affinity chromatography to purify the immunoglobulin
      G1 fraction free of other serum proteins (Ab 1467). These antibodies recognize a
      candidate CFTR protein in the colonic cell line T84, as determined by Western
      blot analysis and by immunoprecipitation and labeling of the precipitate with
      [gamma-32P]ATP in the presence of protein kinase A. Both antibodies precipitated
      CFTR-related polypeptides from four mammalian cell types (HeLa, Bsc-40, HEp-2,
      and Chinese hamster ovary cells) transfected with the full-length CFTR cDNA clone
      using a vaccinia T7 protein expression system. Similar results were observed
      using a yeast CFTR expression system. In each case the Mr values of the bands
      observed were consistent with that expected for the CFTR protein. These
      antibodies should be useful probes for the immunocytochemical localization,
      immunoaffinity purification, and ultimately the functional characterization of
      the CFTR protein.

PMID- 1371642
TI  - Characterization of myocardial Na(+)-Ca2+ exchange in rainbow trout.
AB  - This study compared Na(+)-Ca2+ exchange from the hearts of rainbow trout with
      that from canines. In several respects, trout cardiac Na(+)-Ca2+ exchange is
      functionally similar to that from dogs and other mammals. Trout cardiac Na(+)
      Ca2+ exchange is stimulated approximately 200% after 30-min incubation with 10
      micrograms/ml chymotrypsin at 21 degrees C, similar to mammals. On the other
      hand, both the temperature and pH dependencies are strikingly different between
      the trout and canine myocardial Na(+)-Ca2+ exchange. While canine heart Na(+)
      Ca2+ exchange exhibits a Q10 of greater than 2 (similar to values observed in
      other mammals), that from trout is relatively insensitive to temperature with a
      Q10 of approximately 1.2. The absolute rates of Na(+)-Ca2+ exchange in trout
      heart are four- to sixfold higher than that in mammals when measured at 7 degrees
      C. Furthermore, the temperature insensitivity of trout myocardial Na(+)-Ca2+
      exchange is retained when the exchanger is reconstituted into an asolectin
      bilayer, suggesting that this property is intrinsic to the protein and not
      dependent on species differences in lipid bilayer composition. Trout Na(+)-Ca2+
      exchange is not markedly stimulated by alkaline pH, in contrast to mammals, and
      this characteristic is also maintained after reconstitution. Western blots of
      trout cardiac sarcolemma run on 7.5% sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis react with antibodies raised against the canine Na(+)-Ca2+
      exchanger with a similar pattern of bands (70, 120, and 160 kDa). Furthermore, a
      cDNA probe from canine Na(+)-Ca2+ exchanger hybridizes on Northern blots of trout
      heart mRNA to a 7-kb band, similar to that in mammals. Thus, while important
      functional differences in Na(+)-Ca2+ exchange exist between trout and mammalian
      hearts, the molecular basis is not yet known.

PMID- 1371643
TI  - Regulation of hepatic protein synthesis in chronic inflammation and sepsis.
AB  - The regulation of protein synthesis was determined in livers from control,
      sterile inflammatory, and septic animals. Total liver protein was increased in
      both sterile inflammation and sepsis. The rate of protein synthesis in vivo was
      measured by the incorporation of [3H]phenylalanine into liver proteins in a
      chronic (5 day) intra-abdominal abscess model. Both sterile inflammation and
      sepsis increased total hepatic protein synthesis approximately twofold. Perfused
      liver studies demonstrated that the increased protein synthesis rate in vivo
      resulted from a stimulation in the synthesis of both secreted and nonsecreted
      proteins. The total hepatic RNA content was increased 40% only in sterile
      inflammation, whereas the translational efficiency was increased twofold only in
      sepsis. The increase in translational efficiency was accompanied by decreases in
      the amount of free 40S and 60S ribosomal subunits in sepsis. Rates of peptide
      chain elongation in vivo were increased 40% in both sterile inflammation and
      sepsis. These results demonstrate that sepsis induces changes in the regulation
      of hepatic protein synthesis that are independent of the general inflammatory
      response. In sterile inflammation, the increase in protein synthesis occurs by a
      combination of increased capacity and translational efficiency, while in sepsis,
      the mechanism responsible for accelerated protein synthesis is an increased
      translational efficiency.

PMID- 1371644
TI  - NaCl-dependent expression of amiloride-blockable Na+ channel in Xenopus oocytes.
AB  - RNA was isolated from chicken lower intestine (both colon and coprodeum) and
      injected into Xenopus oocytes. 22Na+ fluxes measured after 1-4 days demonstrated
      the induction of an amiloride-blockable pathway. The Na+ transporter expressed by
      the exogenous RNA had a high affinity to amiloride (inhibitory constant less than
      0.1 microM), but was insensitive to ethylisopropyl amiloride, i.e., it is likely
      to be the apical Na+ channel. Functional channels were readily expressed in
      oocytes injected with RNA derived from chickens fed a low-NaCl diet. On the other
      hand, no channel activity was detected in oocytes injected with RNA isolated from
      chickens fed a high-NaCl diet. Thus the previously reported regulation of
      transport by the dietary NaCl intake involves modulations in the level of mRNA
      that codes either for the Na+ channel or a posttranscriptional regulator of the
      channel.

PMID- 1371645
TI  - Perturbation of regulated secretion in the pancreatic acinar cell line, AR42J.
AB  - The regulated secretory pathway comprises accelerated discharge of proteins in
      response to hormonal stimuli, their presence in secretory granules (SG), and a
      long intracellular residence time. Dexamethasone induction of AR42J results in an
      increase in granule content and responsiveness to cholecystokinin (CCK). We
      studied the effects of conditions implicated in sorting of secretory proteins
      into the regulated pathway using [35S]methionine pulse-chase protocols that
      examine transport of secretory proteins from the rough endoplasmic reticulum
      (RER)----SG and specifically from the Golgi complex (GC)----SG. The latter uses a
      chase at 20 degrees C to allow accumulation of labeled proteins in the trans
      Golgi, followed by a shift to 37 degrees C that initiates their transport to SG
      under test conditions. Quantitation of CCK-8-stimulated discharge of prestored
      amylase and of newly synthesized labeled proteins that have entered SG during the
      chase enables us to examine the effect of perturbants over selected parts of the
      pathway. The effects of acidic intracellular compartments, the cytoskeleton,
      protein synthesis, ATP, and temperature on pre- and post-Golgi entry of proteins
      into the regulated pathway were studied. NH4Cl, monensin, Na azide, incubation at
      20 degrees C, and pertussis toxin retarded RER----SG transport without affecting
      amylase discharge. Only incubation with 20 mM NH4Cl or 1 microM monensin
      inhibited transfer of newly synthesized proteins from the late GC----SG. RER---
      Golgi or intra-Golgi transport thus appears to require ATP and possibly guanosine
      5'-triphosphate (GTP)-binding proteins. Acidic compartments appear to be
      essential for sorting of secretory proteins from the GC----SG.

PMID- 1371646
TI  - Role of polyamines in glucocorticoid effects on pancreatic acinar AR42J cell
      growth and differentiation.
AB  - We previously found that glucocorticoids inhibit growth and increase
      differentiation in rat pancreatic acinar AR42J cells. In the current study, we
      examined the role of polyamines in these effects. Treatment of AR42J cells with
      the ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO)
      inhibited DNA synthesis. Thus polyamines are required for AR42J cell growth.
      However, we have previously shown that dexamethasone (Dex) increased AR42J cell
      ODC activity and mRNA levels. In the current study, we found that Dex treatment
      increased cellular putrescine levels. These increases in ODC and putrescine
      occurred during Dex-induced inhibition of DNA synthesis. Therefore, in AR42J
      cells, ODC activity and polyamine levels are not strictly growth related. To
      examine the requirement for glucocorticoid induction of ODC activity in
      glucocorticoid stimulation of differentiation, we examined the effects of DFMO on
      amylase gene expression and cholecystokinin binding. DFMO reduced cell amylase
      content while having little effect on mRNA levels in both Dex-treated and
      untreated cells. In contrast, DFMO had little effect on control CCK binding but
      inhibited the Dex-induced increase. Thus polyamines are necessary for growth and
      glucocorticoid-induced differentiation of AR42J cells; however, effects of
      glucocorticoids on AR42J cell growth and differentiation are not mediated by
      effects on ODC.

PMID- 1371647
TI  - Postnatal changes in the substance P receptor on rabbit gastric smooth muscle.
AB  - We used radioligand binding to tissue homogenates and isometric contraction of
      muscle strips to characterize the substance P (SP) receptor on gastric smooth
      muscle from 1- (newborn) and 7-day-old and 4- and 11-wk-old (weanling) rabbits.
      Scatchard analysis for newborns was curvilinear, suggesting the presence of
      multiple binding sites. In newborns the dissociation constant (Kd) of high
      affinity binding site was 2.2 +/- 0.3 nM, and the maximum binding (Bmax) was 0.57
      +/- 0.06 pmol/mg DNA. The number of high-affinity binding sites decreased with
      age, disappearing by 11 wk. The Kd for the low-affinity site was more than two
      orders of magnitude greater than that of the high-affinity site. In competitive
      binding studies with [3H]SP, the order of potency for the neurokinins was SP much
      greater than neurokinin A (NKA) greater than neurokinin B (NKB), suggesting that
      the high-affinity binding sites were NK-1 receptors. [125I]NKA is also bound to
      newborn tissue homogenate with high affinity. With [125I]NKA the order was NKA
      greater than SP greater than NKB, suggesting that NK-2 receptors were also
      present. In contraction studies, atropine and tetrodotoxin had no effect on
      tachykinin-stimulated contraction, suggesting solely myogenic tachykinin effects
      on this tissue. In newborn rabbits, the potency and efficacy of SP and NKA were
      similar. The half-maximal effective dose (ED50) of SP was nearly two orders of
      magnitude less in newborn rabbits than in weanlings; the potency of NKA did not
      change.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371648
TI  - Electrical and mechanical effects of acetylcholine and substance P in subregions
      of canine colon.
AB  - Effects of acetylcholine (ACh) and substance P on the electrical and mechanical
      activities of the circular muscle layer of the canine proximal colon were
      studied. Because this muscle layer is bordered by two different pacemaker
      regions, responses from segments containing either a single pacemaker region or
      no pacemaker region were compared with responses of the complete muscle layer.
      Concentration-response relationships for ACh and substance P were similar between
      the various segments, suggesting that receptors for these agonists are expressed
      throughout the layer. The dominant contractile pattern induced by ACh and
      substance P in each segment was a 1- to 3-cycle/min rhythm. In a like manner,
      these agonists also elicited an electrical pattern in which a long-duration slow
      wave occurred one to three times per minute between short-duration slow waves.
      Low concentrations of nifedipine (0.01 microM) selectively antagonized the 1- to
      3-cycle/min rhythm. In circular muscles with no pacemaker region, ACh (1 microM)
      caused depolarization, induced oscillations in membrane potential averaging 24 +/
      5 mV in amplitude and 2.9 +/- 0.9 cycles/min in frequency, and generated
      rhythmic contractions at the same frequency. This "interior" circular muscle was
      functionally innervated by cholinergic excitatory nerves. Exposure to ACh (1
      microM) did not alter the conduction of slow waves through the thickness of the
      circular layer. In summary, the excitatory neurotransmitters, ACh and substance
      P, induce a dominant electrical and contractile rhythm throughout the circular
      muscle layer that is different from the spontaneous rhythms produced at either
      the myenteric or submucosal border.

PMID- 1371649
TI  - Selected polyclonal antibodies and ADH challenge in frog urinary bladder: a label
      fracture study.
AB  - It is clearly established that the changes induced by antidiuretic hormone (ADH)
      in its target epithelial cells result from the insertion in the apical membrane
      of new components that contain channels for water. We have already undertaken an
      initial study of these channels by raising polyclonal antibodies against Triton X
      100 apical extracts from ADH-treated bladders and approached their purification
      by different adsorption steps. In the present study, we used the label-fracture
      technique to investigate the localization of the binding sites of the obtained
      polyclonal antibodies on the apical membrane of ADH-stimulated frog urinary
      bladder. The results obtained clearly demonstrated a preferential labeling by the
      selected antibodies of morphological structures such as the groove arrays and the
      fusion images that are generally accepted as being involved in ADH-induced
      changes in water permeability of the apical membrane.

PMID- 1371650
TI  - Comparison of the effects of BAY K 8644 on cardiac Ca2+ current and Ca2+ channel
      gating current.
AB  - Effects of (-)-BAY K 8644 on Ca2+ channel function were studied in guinea pig
      ventricular myocytes. It was found that the compound has both voltage-dependent
      stimulatory and inhibitory effects on the Ca2+ current (ICa), in agreement with
      prior studies. The basis for these effects was studied by evaluating the effects
      of (-)-BAY K 8644 on the Ca2+ channel gating current. It was found that the
      voltage-dependent inhibitory effects of the drug on ICa could be well explained
      by similar reductions in the amount of gating charge moved. However, the
      stimulatory effect of (-)-BAY K 8644 on ICa could not be simply correlated with
      changes in the amount of gating charge moved. Although the drug produced a shift
      of the charge-voltage relationship to more negative potentials, the drug actually
      reduced the total amount of movable gating charge. Thus it could be demonstrated
      that there are membrane potentials where (-)-BAY K 8644 reduced the Ca2+ channel
      gating current while enhancing ICa. In addition, the drug was found to slow the
      decay of the gating current during repolarization. It seems likely that (-)-BAY K
      8644 has a dual effect on Ca2+ channels: affecting both the voltage dependence of
      gating charge and the relationship between open probability and charge movement.

PMID- 1371651
TI  - Disseminated histoplasmosis with unusual cutaneous lesions in a patient from the
      Philippines.
AB  - The incidence and prevalence of histoplasmosis in Southeast Asia has not been
      extensively described. The first microbiologically documented case of
      disseminated histoplasmosis with cutaneous papulonodules in a 56-year-old woman
      from the Philippines is reported. She presented with fever and generalized
      papulonodular lesions in various stages, which evolved into vesicles with central
      necrosis that resembled molluscum contagiosum with an indurated erythematous
      halo. Biopsies revealed a granulomatous mass of lymphohistiocytic and epithelioid
      cells with intracellular budding yeast cells and dark nuclei. Cultures were
      positive for Histoplasma capsulatum. The patient was treated with amphotericin B
      (3 g) and 5-fluorocytosine (50 mg/kg/day), followed by ketoconazole (400 mg/day).
      Her clinical course was complicated by intractable hemolytic anemia that was
      initially treated with corticosteroids. A splenectomy was subsequently performed.
      Pneumonia and a brain abscess caused by Nocardia asteroides were secondary
      complications. Nine months after her admission, repeat testing was diagnostic for
      systemic lupus erythematosus. This patient serves to re-emphasize that cutaneous
      lesions in an immunocompromised patient must be evaluated by biopsy and culture
      analysis. Disseminated histoplasmosis in the immunocompromised host may present
      with unusual cutaneous lesions, and must be considered even in a nonendemic area.

PMID- 1371652
TI  - Serial serum C-reactive protein levels as an aid to the management of
      melioidosis.
AB  - Of 46 patients with clinical melioidosis, 35 (22 culture-positive and 13 culture
      negative) had relatively uneventful disease courses, with elevated serum C
      reactive protein (CRP) concentrations (greater than 5 mg/dl) that decreased with
      the commencement of appropriate antibiotic therapy, and continued to show an
      uninterrupted decrease (mean 29.4 days, range 12-52 days) to the normal range
      (less than 1 mg/dl), with resolution of their infections. In five culture
      positive patients with complicated disease courses, CRP concentrations remained
      elevated (greater than 5 mg/dl) until the underlying disorders were successfully
      managed, or until the antibiotic regimen was changed, and CRP values then
      decreased to the normal range. During surveillance, elevated CRP concentrations
      (greater than 10 mg/dl) led to the diagnosis of reactivation of infection in
      three afebrile patients, while the serum CRP values in other patients remained
      within the normal range in the absence of intercurrent complications. The CRP
      estimations may be helpful in ascertaining active infection in patients with low
      serum levels of specific IgM antibody, and serial measurements of serum CRP in
      patients with clinical melioidosis may be useful in determining the optimal
      duration of treatment and for detecting occult or unresolved infection with
      Pseudomonas pseudomallei.

PMID- 1371653
TI  - Diamorphine toxicity.

PMID- 1371655
TI  - Exercise-induced pulmonary hemorrhage in horses with experimentally induced
      allergic lung disease.
AB  - The lungs of sensitized horses were exposed to aerosolized ovalbumin. Some horses
      (n = 4) were given ovalbumin in 1 lung only, whereas in others (n = 7), ovalbumin
      or vehicle were inoculated in the cranial, ventral, and caudal regions of the
      caudal lung lobe. Horses were exercised 5 hours after ovalbumin exposure.
      Immediately before exercise, endoscopy failed to reveal any abnormality. After
      exercise, endoscopic examination of horses subjected to unilateral ovalbumin
      exposure revealed extensive blood in airways leading to the exposed lung in all
      horses. Blood was not observed in the airways leading to the control lung. Mean
      (+/- SEM) minimum volume of the exposed and control lungs was 9.5 +/- 1.5 and 5.5
      +/- 1.6 L, respectively; this difference was statistically significant (P less
      than 0.05). Bronchoscopy of horses subjected to regional ovalbumin or vehicle
      exposure and exercise revealed a small amount of blood-tinged fluid in the
      bronchi serving the regions of the lung inoculated with ovalbumin. Minimum
      volumes of such regions were not significantly different from one another.
      However, their minimum volume was significantly (P less than 0.05) larger than
      that of vehicle-inoculated regions. Gross and histologic examination confirmed
      inflammation and hemorrhage in the ovalbumin-exposed, but not the control lungs
      or lung regions. Thus, exercise can cause blood from an injured region of lung to
      appear in the larger airways. Regional differences in lung structure and function
      do not influence the appearance of blood in the airways.

PMID- 1371654
TI  - Mechanism of action of atracurium on airways.
AB  - Histamine-releasing drugs may produce significant effects on airways in high-risk
      populations. To determine if clinically relevant doses of atracurium produce
      adverse effects on airways, we measured changes in airway resistance in the lung
      periphery of anesthetized Basenji-Greyhound dogs before and after intravenous
      (iv) administration of atracurium. A wedged bronchoscope technique was used to
      measure collateral system resistance (Rcs). After a stable baseline was obtained,
      atracurium (1.2 or 0.5 mg/kg) or histamine (200 micrograms) were administered as
      an iv bolus, and percent increase in Rcs was calculated. On separate days dogs
      were pretreated with the histamine 1 receptor antagonist, chlorpheniramine (0.2
      mg/kg iv), with or without atropine (0.2 mg/kg iv) and ranitidine (0.75 mg/kg iv)
      and the experiment repeated. Histamine (200 micrograms) increased Rcs 97 +/- 24%
      at 30 s (8 sublobar segments), whereas a second dose increased Rcs 77 +/- 15%.
      Pretreatment with chlorpheniramine (0.2 mg/kg iv) totally prevented increases in
      Rcs (9 sublobar segments). Atracurium (1.2 mg/kg) increased Rcs to 174 +/- 35% at
      3 min (14 sublobar segments), whereas 0.5 mg/kg had little effect (10 sublobar
      segments). A second bolus of atracurium (1.2 mg/kg) increased Rcs to only 54 +/-
      14% (P less than 0.01). Chlorpheniramine pretreatment (0.2 mg/kg iv) reduced the
      response to the initial dose of atracurium to only 26 +/- 14% (10 sublobar
      segments). Pretreatment with a combination of atropine and chlorpheniramine (4
      sublobar segments), or ranitidine and chlorpheniramine (5 sublobar segments), did
      not attenuate the increase in Rcs significantly more than chlorpheniramine
      pretreatment alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371656
TI  - Development of monoclonal antibody ELISA for simultaneous detection of bovine
      coronavirus, rotavirus serogroup A, and Escherichia coli K99 antigen in feces of
      calves.
AB  - A rapid ELISA was developed for simultaneous detection of bovine coronavirus
      (BCV), rotavirus (RV) serogroup A, and Escherichia coli K99 antigen in feces of
      calves. A mixture of 3 monoclonal antibodies specific for BCV, RV, or K99 was
      used successfully to capture the antigens; the same antibodies labeled with
      peroxidase were used to detect BCV, RV, or K99. The triple ELISA was compared
      with standard reference diagnostic methods by examining feces from experimentally
      and naturally infected and healthy calves. All the components of the test were
      highly specific (greater than 90%) and sensitive (BCV, 77%; K99, 93%; RV, 100%)
      when used in a format requiring short incubation steps at 20 C and visual
      recording of results.

PMID- 1371657
TI  - Presenting research to perioperative audiences. Avoiding the five deadly sins.

PMID- 1371658
TI  - Degradation of 2-methylbenzoic acid by Pseudomonas cepacia MB2.
AB  - We report the isolation of Pseudomonas cepacia MB2, believed to be the first
      microorganism to utilize 2-methylbenzoic acid as the sole carbon source. Its
      growth range included all mono- and dimethylbenzoates (with the exception of 2,5-
      and 2,6-dimethylbenzoates) and 3-chloro-2-methylbenzoate (but not 4- or 5-chloro
      2-methylbenzoate) but not chlorobenzoates lacking a methyl group. 2
      Chlorobenzoate, 3-chlorobenzoate, and 2,3-, 2,4-, and 3,4-dichlorobenzoates
      inhibited growth of MB2 on 2-methylbenzoate as a result of cometabolism to the
      corresponding chlorinated catechols which blocked the key enzyme catechol 2,3
      dioxygenase. A metapyrocatechase-negative mutant, MB2-G5, showed accumulation of
      dimethylcatechols from 2,3- and 3,4-dimethylbenzoates, and phenols were detected
      in resting-cell transformation extracts bearing the same substitution pattern as
      the original substrate, presumably following thermal degradation of the
      intermediate dihydrodiol. 2-Methylphenol was also found in extracts of the mutant
      cells with 2-methylbenzoate. These observations suggested a major route of
      methylbenzoate metabolism to be dioxygenation to a carboxy-hydrodiol which then
      forms a catechol derivative. In addition, the methyl group of 2-methylbenzoate
      was oxidized to isobenzofuranone (by cells of MB2-G5) and to phthalate (by cells
      of a separate mutant that could not utilize phthalate, MB2-D2). This pathway also
      generated a chlorinated isobenzofuranone from 3-chloro-2-methylbenzoate.

PMID- 1371659
TI  - Variations in rRNA content of marine Vibrio spp. during starvation-survival and
      recovery.
AB  - The degree and temporal context of variations in ribosome content during nutrient
      starvation of two copiotrophic marine bacteria, Vibrio alginolyticus and Vibrio
      furnissii, have been examined. The organisms were starved either by nutritional
      shift-down or by consumption of limiting nutrients resulting from growth into
      stationary phase. Measurements of the amount of hybridization to 16S rRNA
      specific probes revealed that the cells retained between 10 and 26% of their
      original rRNA content after 15 days of starvation. In V. alginolyticus, losses in
      stationary-phase cells occurred rapidly (1 to 2 days), whereas cells shifted into
      starvation remained larger and retained considerably more rRNA. The ability of V.
      alginolyticus to recover from starvation was assessed after cells were maintained
      for 2, 8, and 15 days in nutrient-depleted medium. The pattern of recovery at the
      level of rRNA accumulation depended upon the duration of nutrient deprivation and
      the manner in which it was imposed. Stationary-phase cells starved for 2 days had
      only slight relative increases in rRNA levels after excess nutrients were added.
      As the duration of starvation lengthened to 8 and 15 days, increasingly greater
      amounts of rRNA (30 and 70 times preenrichment values, respectively) were
      transcribed after nutrient enrichment. Shift-down cells recovered from 2 and 8
      days of starvation without extensive rRNA production. After 15 days, nutrient
      enrichment caused 16S rRNA levels to increase 30-fold. The results indicate that
      the mechanisms controlling starvation-survival in these marine bacterial species
      are linked to the physiological state at the onset of starvation and that the
      subsequent pattern of recovery will depend upon how starvation was initiated.

PMID- 1371660
TI  - Influence of elevated temperature on starch hydrolysis by enterotoxin-positive
      and enterotoxin-negative strains of Clostridium perfringens type A.
AB  - Enterotoxin-positive (Ent+) and enterotoxin-negative (Ent-) strains of
      Clostridium perfringens were cultured in Duncan-Strong sporulation medium
      containing starch at 37 and 46 degrees C. At 37 degrees C, all strains degraded
      starch and sporulated well. However, only Ent- strains could hydrolyze starch,
      grow extensively, and sporulate at 46 degrees C. Growth, sporulation, and starch
      hydrolysis by Ent+ strains at 46 degrees C were equivalent to those obtained at
      37 degrees C when alpha-amylase was added to the cultures during growth. The
      total amount of extracellular plus intracellular amylase in cultures of Ent+
      strains was significantly less in cells incubated at 46 degrees C than in cells
      incubated at 37 degrees C. These results contradict an earlier report that Ent+
      strains cannot sporulate well near their optimal growth temperature (R. G. Labbe
      and C. L. Duncan, Can. J. Microbiol. 20:1493-1501, 1974) and suggest that
      synthesis of alpha-amylase in Ent+ strains is regulated by temperature.

PMID- 1371661
TI  - Survival, stress resistance, and alterations in protein expression in the marine
      vibrio sp. strain S14 during starvation for different individual nutrients.
AB  - The response of the marine Vibrio sp. strain S14 to starvation for carbon,
      nitrogen, or phosphorus and to simultaneous depletion of all these nutrients
      (multiple-nutrient starvation) was examined with respect to survival, stress
      resistance, quantitative and qualitative alterations in protein and RNA
      synthesis, and the induction of the stringent control. Of the conditions tested,
      carbon starvation and multiple-nutrient starvation both promoted long-term
      starvation resistance and a rapid induction of the stringent control, as deduced
      from the kinetics of RNA synthesis. Carbon- and multiple-nutrient-starved cells
      were also found to become increasingly resistant to heat, UV, near-UV, and CdCl2
      stress. Nitrogen- and phosphorus-starved cells demonstrated a poor ability to
      survive in the presence of carbon and did not develop a marked resistance to the
      stresses examined. The carbon, nitrogen, and phosphorus starvation stimulons
      consisted of about 20 proteins each, while simultaneous starvation for all the
      nutrients elicited an increased synthesis of 42 polypeptides. Nine common
      proteins were found to be induced regardless of the starvation condition used and
      were tentatively termed general starvation proteins. It was also demonstrated
      that the total number of proteins induced in response to multiple-nutrient
      starvation was not a predictable sum of the different individual starvation
      stimulons. Multiple-nutrient starvation induced 14 proteins which were not
      detected at increased levels of expression in response to individual starvation
      conditions. Furthermore, four out of five phosphorus starvation-specific
      polypeptides were not induced during simultaneous starvation for phosphorus,
      nitrogen, and carbon. The results are discussed in light of the physiological
      alterations previously described for Vibrio sp. strain S14 cells starved for
      carbon, nitrogen, and phosphorus simultaneously.

PMID- 1371662
TI  - HLA-D region genes and rheumatoid arthritis (RA): importance of DR and DQ genes
      in conferring susceptibility to RA.
AB  - The distribution of HLA-D region antigens was studied in three groups (I, IIa,
      and IIb) of patients with rheumatoid arthritis (RA): group I comprised 43
      patients with mild, non-progressive RA, controlled by non-steroidal anti
      inflammatory drugs without progression or erosions; group II comprised 94
      patients with severe disease, who had earlier been treated with non-steroidal
      anti-inflammatory drugs and all had incomplete response requiring treatment with
      gold (sodium aurothiomalate). Of these, 46 patients (group IIa) responded to gold
      and the disease was well controlled, and the remaining 48 patients (group IIb)
      did not respond to gold and developed gold induced toxic reactions, including
      thrombocytopenia or proteinuria, or both. HLA-D region antigens were defined by
      serological and molecular (Southern blot analysis and oligonucleotide typing)
      techniques. The results show that DR4 was significantly increased in all three
      groups of patients. The prevalence of DR1, or DR1 in DR4 negative patients, and
      DR3 and DR4 associated DQw7 specificities, however, showed differences in these
      three groups of patients. The prevalence of DR1 and of DR1 in DR4 negative
      patients was increased only in patients with mild (group I) RA, but not in
      patients with severe (groups IIa and IIb) disease. On the other hand, the
      prevalence of DR4 associated DQw7 was significantly increased in patients with
      severe disease, but not in patients with mild RA. In addition, DR3 was
      significantly increased only in patients with severe disease who developed gold
      induced toxic reactions (group IIb). These data suggest that the HLA-D region
      genes which cause susceptibility to mild RA may be different from those causing
      susceptibility to severe RA. The results suggest that both DR and DQ (A, B) genes
      may be important in conferring susceptibility to RA: DR in mild disease and DQ in
      severe RA.

PMID- 1371664
TI  - Palliative intubation for dysphagia in patients with carcinoma of the esophagus.
AB  - One hundred seven consecutive patients seen over a 6-year period with dysphagia
      secondary to advanced primary carcinoma of the esophagus underwent intubation.
      One hundred five patients underwent pulsion intubation. In 2 patients pulsion
      intubation was not possible, and laparotomy and traction intubation was
      performed. For the intubated group there were 65 men and 40 women (ratio, 1.6:1),
      with a mean age of 71.3 +/- 10.5 years (range, 36 to 92 years). Of the 105
      patients who had pulsion intubation, a perforation developed in 11 (10.5%), which
      was responsible for the death of 4 patients (3.8%). A further 3 patients died of
      malignant cachexia, which resulted in an overall mortality of 6.7%. Late
      complications included tube displacement (4 patients; 3.8%) and tube obstruction
      (32 patients; 30.5%). Tube obstruction was due to advancement of malignant
      disease in 26 patients (81.2%) and food bolus impaction in the remaining 6
      patients (18.8%). Pulsion intubation for advanced carcinoma of the esophagus can
      be performed with a low morbidity and early mortality. However, there is a
      substantial long-term morbidity of tube obstruction in almost a third of
      survivors.

PMID- 1371663
TI  - Different capabilities of monocytes from patients with systemic lupus
      erythematosus and rheumatoid arthritis to induce glycosylation alterations of
      acute phase proteins in vitro.
AB  - The effect of conditioned medium on the biosynthesis and glycosylation profile of
      acute phase proteins secreted by the human hepatoma cell line Hep G2 was studied.
      Conditioned medium was prepared from nonactivated [CM-LPS(-)] and ex vivo
      lipopolysaccharide activated [CM-LPS(+)] monocytes from eight patients with
      active rheumatoid arthritis (RA), five patients with active systemic lupus
      erythematosus (SLE), and seven healthy subjects. The biosynthesis of albumin,
      alpha 1-antichymotrypsin and alpha 1-proteinase inhibitor and the profile of
      glycosylation of proteinase inhibitor were analysed. CM-LPS(-) from patients with
      SLE had a similar effect to CM-LPS(-) from healthy subjects. In contrast, CM-LPS(
      ) from patients with RA had the same effect as CM-LPS(+) from healthy donors. A
      similar effect to that of CM-LPS(+) of healthy subjects was seen with CM-LPS(+)
      from patients with SLE and with CM-LPS(+) from patients with RA. The treatment of
      CM-LPS(+) with antibodies against interleukin 6 neutralised most of its ability
      to induce changes in the biosynthesis and glycosylation of acute phase proteins.
      Antibodies to interleukin 1 and tumour necrosis factor alpha had only a limited
      effect on the ability of CM-LPS(+) to induce changes of albumin and alpha 1
      antichymotrypsin syntheses, whereas they had no effect on the biosynthesis and
      glycosylation of proteinase inhibitor. These results indicate that: (a) monocytes
      isolated from patients with active SLE and active RA have different capabilities
      of inducing alterations of acute phase proteins in vitro; (b) ex vivo activation
      of monocytes from patients with SLE leads to the full induction of its
      capabilities to change acute phase proteins, whereas the activation of monocytes
      from patients with RA has no additive effects; and (c) interleukin 6 seems to be
      a major cytokine involved in the regulation of the glycosylation pattern of acute
      phase proteins.

PMID- 1371665
TI  - Platelet protection by aprotinin in cardiopulmonary bypass: electron microscopic
      study.
AB  - To evaluate the functional integrity of platelets in patients administered the
      proteinase inhibitor aprotinin during cardiopulmonary bypass, 20 patients
      undergoing a complicated and prolonged open heart operation were studied. They
      were randomized to receive either a high dose of aprotinin (total dose, 6 to 7 x
      10(6) KIU) before and during cardiopulmonary bypass (10 patients) or a placebo
      (10 patients). Blood samples were collected preoperatively, at the termination of
      bypass, and 90 minutes thereafter to assess platelet count and aggregation on
      extracellular matrix, which was studied by scanning electron microscopy. On a
      scale of 1 to 4, mean preoperative platelet aggregation grades were similar in
      both groups (3.5 +/- 0.5). Postoperatively, at the termination of cardiopulmonary
      bypass and 90 minutes thereafter, all 10 patients treated with aprotinin revealed
      normal, unchanged platelet aggregation (grade, 3.5 +/- 0.5), whereas all placebo
      treated patients showed severely disturbed aggregation (grade, 1.4 +/- 0.5) (p
      less than 0.001). The platelet count was similar in both groups before and after
      operation (preoperatively, 182 +/- 75 x 10(9)/L and 146 +/- 30 x 10(9)/L, and
      postoperatively, 87 +/- 13 x 10(9)/L and 80 +/- 27 x 10(9)/L for the aprotinin
      and placebo groups, respectively). Total 24-hour postoperative bleeding and blood
      requirement were significantly lower in the aprotinin group (371 +/- 84 mL and 2
      +/- 0.7 units, respectively) compared with the placebo group (608 +/- 28 mL and
      3.4 +/- 1.3 units, respectively) (p less than 0.01). These results demonstrate
      that improved postoperative hemostasis is directly related to the complete
      preservation of platelet function achieved by the protective properties of
      aprotinin.

PMID- 1371666
TI  - Retention of epidermal growth factor receptors in the endoplasmic reticulum of
      adenovirus-infected cells.
AB  - The epidermal growth factor (EGF) receptor is down-regulated during early
      infection with adenovirus, and this has been attributed to accelerated
      internalization and degradation of the receptor in the absence of ligand (Carlin,
      Tollefson, Brady, Hoffman & Wold (1989) Cell 57, 135-144]. Using pulse-chase
      analysis, we show that loss of functional EGF receptors after infection of human
      KB and A431 cells with adenovirus type 5 is accompanied by accumulation of a
      receptor precursor that remains fully sensitive to endoglycosidase H, indicative
      of retention in the endoplasmic reticulum. A truncated receptor, normally
      secreted by A431 cells, also accumulates intracellularly as an endoglycosidase H
      sensitive precursor. In no case is the block in intracellular transport of EGF
      receptors complete. We conclude that both stimulation of EGF receptor
      internalization and degradation and inhibition of intracellular transport of
      newly synthesized EGF receptors from the endoplasmic reticulum towards the cell
      surface contribute to EGF receptor down-regulation in adenovirus-infected cells.

PMID- 1371667
TI  - Glucose transporter expression and glucose utilization in skeletal muscle and
      brown adipose tissue during starvation and re-feeding.
AB  - Starvation (48 h) decreased the concentration of mRNA of the insulin-responsive
      glucose transporter isoform (GLUT 4) in interscapular brown adipose tissue (IBAT)
      (56%) and tibialis anterior (10%). Despite dramatic [7-fold (tibialis anterior)
      and 40-fold (IBAT)] increases in glucose utilization after 2 and 4 h of chow re
      feeding, no significant changes in GLUT 4 mRNA concentration were observed in
      these tissues over this re-feeding period. The results exclude changes in GLUT 4
      mRNA concentration in mediating the responses of glucose transport in these
      tissues to acute re-feeding after prolonged starvation.

PMID- 1371668
TI  - Type II intermediate-filament proteins from wool. The amino acid sequence of
      component 5 and comparison with component 7c.
AB  - Component 5 is one of the four type II intermediate-filament proteins found in
      the hard keratin wool. It was isolated as the S-carboxymethyl derivative from
      Merino wool and its amino acid sequence was determined by manual and automatic
      sequencing of peptides produced by chemical and enzymic cleavage. Component 5 is
      an N-terminally blocked molecule of 503 residues and Mr (not including the
      blocking group) of 56,600. The blocking group has not been identified. The amino
      acid sequence of component 5 shows 77% sequence identity with that of component
      7c, another type II wool intermediate-filament protein [Sparrow, Robinson,
      McMahon & Rubira (1989) Biochem. J. 261, 1015-1022]. The sequence similarity
      extends from the N-termini of the two molecules to residue 459 (component 5
      sequence); however, there is no recognizable sequence similarity in the remaining
      C-terminal 43 amino acid residues. Details of procedures used in determining the
      sequence of component 5 have been deposited as a Supplementary Publication SUP
      50168 (80 pages) at the British Library Document Supply Centre, Boston Spa,
      Wetherby, West Yorkshire, LS23 7BQ, U.K., from whom copies can be obtained on the
      terms indicated in Biochem. J. (1992) 281, 5. The information comprises: (1)
      details of chemical and enzymic methods used for cleavage of component 5, peptide
      CN1, the peptide mixture CN2/3 and various other peptides, (2) details of the
      procedures used for the fractionation and purification of peptides from (1),
      including Figures showing the elution profiles from the chromatographic steps
      used, and (3) details of the method used to determine the C-terminal sequence of
      component 5.

PMID- 1371669
TI  - Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic
      in dexamethasone-treated rats.
AB  - The administration of insulin-like growth factor-I (IGF-I) via subcutaneously
      implanted osmotic pumps partially reversed a catabolic state produced by the co
      administration of 20 micrograms of dexamethasone/day to 150 g male rats. Marked
      dose-dependent effects on body weight and nitrogen retention were produced, with
      the highest IGF-I dose, 695 micrograms/day, giving a 6 g increase in body weight
      over 7 days, compared with a 19 g loss in the dexamethasone-only group and an 18
      g gain in pair-fed controls. Two IGF-I analogues that bind poorly to IGF-binding
      proteins, the truncated form, des(1-3)IGF-I, and a variant with an N-terminal
      extension as well as arginine at residue 3, LR3IGF-I, were approx. 2.5-fold more
      potent than IGF-I. The response with LR3IGF-I was particularly striking because
      this peptide binds 3-fold less well than IGF-I to the type 1 IGF receptor. The
      increased potencies of the IGF-I variants may relate to the substantially
      increased plasma levels of IGF-binding proteins, particularly IGFBP-3, produced
      by the combined treatment of dexamethasone with IGF-I or the variants. These
      binding proteins would be expected to decrease the transfer of IGF-I, but not
      that of the variants, from blood to tissue sites of action. Measurements of
      muscle protein synthesis at the end of the treatment period and muscle protein
      breakdown by 3-methylhistidine (3MH) excretion throughout the experiment
      indicated coordinate anabolic effects of the IGF peptides on both processes. Thus
      3MH excretion was decreased at the highest IGF-I dose from 83.5 +/- 4.2 (S.E.M.)
      mumol/kg per 7 days to 65.1 +/- 2.2, compared with 54.9 +/- 1.2 in the pair-fed
      controls. Part of this response in 3MH excretion may have reflected a decrease in
      gut protein breakdown, because IGF-I and especially the IGF analogues increased
      the gut weight by up to 45%. Notwithstanding the effects on protein synthesis and
      breakdown, the fractional carcass weights remained low in the IGF-treated groups,
      although the increase in total carcass weight reflected nitrogen rather than fat
      gain. The dexamethasone-induced changes in liver, spleen and heart weight were
      restored towards normal by the IGF treatment. The experiment demonstrates the
      potential of IGF-I treatment of catabolic states and especially the value of
      modified forms of growth factors that bind weakly to IGF-binding proteins.

PMID- 1371671
TI  - Cyclic AMP-dependent modulation of cardiac Ca channels expressed in Xenopus
      laevis oocytes.
AB  - Cyclic AMP-dependent modulation of cardiac L-type voltage-dependent Ca channel
      (VDCC) has been probed in Xenopus laevis oocytes injected with poly(A+) RNA from
      rat heart. A 2 to 3 fold increase of the Ba current amplitude was routinely
      obtained upon microinjection of cAMP (50-500 microM). Inhibition of protein
      kinase A (PKA) dramatically reduced the Ba current amplitude, indicating that
      cAMP-dependent modulation plays an important role in maintaining the basal
      activity of expressed Ca channels. Moreover, the effects of the DHP agonist Bay K
      8644 on kinetic properties of expressed Ba current (IBa,C) were dependent on PKA
      activation. The results suggest that most expressed cardiac L-type VDCCs are
      phosphorylated and demonstrate that reconstitution in Xenopus oocytes is a
      suitable approach to address how phosphorylation regulates VDCC activity.

PMID- 1371672
TI  - In the GluR1 glutamate receptor subunit a glutamine to histidine point mutation
      suppresses inward rectification but not calcium permeability.
AB  - Recent papers have described glutamine to arginine point mutations of the cloned
      AMPA/Kainate receptor subunits that alter current-voltage relationship and
      suppress Ca2+ permeability, thus linking these two characteristics. We describe a
      glutamine to histidine mutation at the same position, which alters current
      voltage relationship but retains Ca2+ permeability, thus dissociating the two
      properties.

PMID- 1371670
TI  - Cellular mechanism of the insulin-like effect of growth hormone in adipocytes.
      Rapid translocation of the HepG2-type and adipocyte/muscle glucose transporters.
AB  - The cellular mechanism whereby growth hormone (GH) acutely stimulates adipocyte
      glucose uptake was studied in cultures of primary rat adipocytes differentiated
      in vitro. Preadipocytes were isolated by collagenase digestion of inguinal fat
      pads from young rats and were differentiated in the presence of 3-isobutyl-1
      methylxanthine, insulin and dexamethasone. The development of an adipocyte
      morphology (i.e. lipid inclusions) was observed over 6 days after initiation of
      differentiation. Coincident with this phenotypic change was an increase in
      glyceraldehyde-3-phosphate dehydrogenase (GPDH) activity and in cellular content
      of the HepG2-type (Glut1) and adipocyte/muscle (Glut4) glucose transporter
      isoforms as determined by Western immunoblotting of total cellular protein. Age
      matched undifferentiated cells expressed the Glut1 transporter and low levels of
      GPDH, but neither accumulated lipid nor exhibited measurable expression of the
      Glut4 protein. On day 6 after the initiation of differentiation, GH and insulin
      stimulated 2-deoxy[14C]glucose uptake in a dose- and time-dependent fashion in
      adipocytes cultured under serum-free conditions for at least 15 h. Western-blot
      analysis of subcellular fractions revealed that both GH and insulin rapidly
      (within 20 min) stimulated translocation of the Glut1 and Glut4 proteins from a
      low-density microsomal fraction to the plasma membrane. Confirmatory evidence was
      provided in immunocytochemical experiments utilizing antisera directed against
      the C-terminal region of the Glut4 protein and a fluorescein isothiocyanate
      labelled second antibody. Observation of the cells via confocal laser microscopic
      imaging was consistent with glucose transporter redistribution from an
      intracellular region to the plasma membrane after treatment with GH or insulin.
      On the basis of these data, we suggest that the insulin-like effect of GH on
      adipocyte glucose transport involves translocation of the Glut1 and Glut4
      proteins to the plasma membrane. Furthermore, stimulation of glucose-transporter
      translocation by both GH and insulin may indicate a common cell signalling
      element between the adipocyte GH and insulin receptors or, alternatively, the
      existence of multiple cellular mechanisms for stimulating glucose-transporter
      translocation.

PMID- 1371673
TI  - Concomitant expression of receptor subtype and isopeptide of endothelin by human
      adrenal gland.
AB  - We studied whether specific receptors for endothelin (ET) isopeptide exist in
      human aldosterone-producing adenoma and normal adrenal cortex, and whether ET
      isopeptides are produced by human adrenal gland. Competitive binding studies
      using [125I]ET-1 as a radioligand revealed the presence of a single class of high
      affinity binding sites for ET-1 with the apparent KD of 70 +/- 31 pM and Bmax of
      226 +/- 139 fmol/mg protein in adenoma membranes almost comparable to those in
      adjacent normal cortex. The apparent Ki for ET-2 and ET-3 were 89 +/- 33 pM and
      82 +/- 16 pM, respectively. Northern blot analysis of poly(A)+ RNA of adenoma and
      adjacent normal cortex using cDNAs for ET receptor subtype (ETA, ETB) and ET
      isopeptide (ET-1, ET-3) as probes revealed that ETA and ETB receptors as well as
      ET isopeptides (preproET-1, preproET-3) are concomitantly expressed in both
      tissues. Our data demonstrate for the first time that ET receptor subtype (ETA
      and ETB) and ET isopeptide (ET-1 and ET-3) are concomitantly expressed by human
      adrenal cortex, suggesting the potential role of ETs as a local mediator in human
      adrenal gland.

PMID- 1371674
TI  - Interleukin-10 (IL-10) inhibits the induction of nitric oxide synthase by
      interferon-gamma in murine macrophages.
AB  - A murine macrophage cell line, J774, expresses high levels of the enzyme nitric
      oxide synthase (NOS) and produces large amounts of nitric oxide (NO) when
      activated with recombinant interferon (IFN)-gamma and a low concentration of LPS
      (10 ng/ml). Both the expression of NOS and the production of NO were inhibited by
      recombinant IL-10 in a dose-dependent manner. The inhibition was effective only
      when the cells were pretreated with IL-10; addition of IL-10 at the same time or
      after IFN-gamma activation was without effect. These results demonstrate that IL
      10, a product of Th2 (helper T lymphocyte 2) cells, can antagonise the function
      of IFN-gamma, a product of Th1 cells, by modulating the mechanism of synthesis of
      nitric oxide in the macrophages.

PMID- 1371675
TI  - Evidence for polyamine channels in protoplasts and vacuoles of Arabidopsis
      thaliana cells.
AB  - The presence of ion channels permeable to polyamines in the plasma membrane and
      tonoplast of Arabidopsis thaliana cultured cells was investigated by means of the
      patch-clamp technique in the whole-cell configuration. Evidence is shown for
      channels, activated by depolarizations in protoplasts and by hyperpolarizations
      in vacuoles, with slow time course of activation, permeable to putrescine,
      spermidine and spermine.

PMID- 1371676
TI  - Thrombospondin sequence motif (CSVTCG) is responsible for CD36 binding.
AB  - To clarify the role of CD36 as a TSP receptor and to investigate the mechanisms
      of the TSP-CD36 interaction, transfection studies were performed using CD36-cDNA
      in a CDM8 plasmid. Jurkat cells transfected with CD36 cDNA express an 88kD
      membrane surface protein and acquire the ability to bind thrombospondin. The TSP
      amino acid sequence, CSVTCG, mediates the interaction of thrombospondin with
      CD36. CD36 transfectants but not control transfectants bind radiolabeled
      tyrosinated peptide (YCSVTCG). The hexapeptide inhibits thrombospondin expression
      on activated human platelets and results in diminished platelet aggregation.
      CSVTCG-albumin conjugates support CD36-dependent adhesion of tumor cells. We
      conclude that the CSVTCG repeat sequence is a crucial determinant of CD36
      thrombospondin binding.

PMID- 1371678
TI  - Inhibition of selectin-dependent tumor cell adhesion to endothelial cells and
      platelets by blocking O-glycosylation of these cells.
AB  - Expression of sialosyl-Le(x) (SLe(x)) and sialosyl-Le(a) (SLe(a)) on tumor cell
      lines HL60, Colo205, and U937 was greatly suppressed by application of benzyl
      alpha-GalNAc for inhibition of O-linked carbohydrate chain extension, which
      resulted in reduced adhesion of tumor cells to activated endothelial cells or
      platelets mediated by ELAM-1 (E-selectin) or GMP-140 (P-selectin). Inhibitors or
      modifiers of N-glycosylation had no effect on expression of SLe(x) or SLe(a) in
      these tumor cells. These findings suggest the possibility that targeting of O
      glycosylation inhibitors or modifiers to tumor cells may effectively suppress
      metastatic potential.

PMID- 1371677
TI  - FK-506 binding protein from Tolypocladium inflatum: resistance of FKBP/FK-506
      complex against proteolysis.
AB  - A 12-kDa peptidyl-prolyl-cis/trans-isomerase was purified 225-fold to homogeneity
      from the cyclosporin producing fungus Tolypocladium inflatum. The enzyme is
      highly sensitive to the immunosuppressant FK-506 but not to cyclosporin and thus
      belongs to the class of FK-506 binding proteins (FKBP). Interestingly the FKBP/FK
      506 complex is resistant against proteolytic digestion by the endoproteases GluC
      and LysC, in contrast to the free FKBP, which is readily cleaved by these
      proteases. This protection may play a role in the effects of FK-506 in the living
      cell.

PMID- 1371679
TI  - Involvement of the "tethered-ligand" receptor in thrombin inhibition of platelet
      adenylate cyclase.
AB  - Thrombin is thought to activate platelets through multiple signaling pathways.
      Recently a new thrombin receptor was identified (Vu et al., Cell 64:1057-1068,
      1991) that recognizes alpha-thrombin's anion-binding exosite. Thrombin cleaves
      this receptor generating a new N-terminal ("tethered-ligand") that activates the
      receptor. We report here that this receptor is involved in alpha-thrombin
      inhibition of platelet adenylate cyclase, a process thought mediated by
      thrombin's high-affinity pathway. In gel-filtered human platelets, iloprost
      stimulated cAMP levels were lowered by alpha- and zeta-thrombin addition and, to
      a much lesser extent, by gamma-thrombin. The alpha- and zeta-thrombin mediated
      decreases in cAMP were prevented by the thrombin anion-binding exosite inhibitor,
      BMS 180742, implying that binding to thrombin's anion-binding exosite was
      required. The iloprost-stimulated increase in cAMP was also reversed (in a
      concentration-dependent fashion) by a peptide mimicking the new N-terminal of the
      "tethered-ligand" thrombin receptor (SFLLRNPNDKYEPF). In broken cell
      preparations, platelet adenylate cyclase activity was also inhibited by
      SFLLRNPNDKYEPF (but not by a similar peptide used as a control, FSLLRNPNDKYEPF).
      These results support the hypothesis that thrombin inhibition of platelet
      adenylate cyclase activity is mediated, at least in part, via the "tethered
      ligand" receptor. Moreover, this data is consistent with the "tethered-ligand"
      receptor mediating the high affinity actions of alpha-thrombin.

PMID- 1371681
TI  - Recombinant E-selectin-protein mediates tumor cell adhesion via sialyl-Le(a) and
      sialyl-Le(x).
AB  - E-selectin (previously known as ELAM-1) is one of the adhesion molecules
      expressed on activated endothelium. Here we show that HL-60 cells express sialyl
      Le(x), but not Sialyl-Le(a) on their surface, a colon carcinoma cell line COLO
      205 express both these epitopes and another colon carcinoma COLO 320 does not
      express either one of them. HL-60 and COLO 205 cell adhere strongly to E-selectin
      coated microwells, whereas COLO 320 does not adhere at all to E-selectin. Finally
      we provide evidence that monoclonal anti-sialyl-Le(x) can abolish part of the
      adherence of HL-60 cells to recombinant E-selectin. The adherence of COLO 205
      cells can be decreased by either monoclonal anti-sialyl-Le(a) or anti-sialyl
      Le(x) antibodies. These results indicate that cell-associated sialylated
      carbohydrate moieties can act as ligands for recombinant E-selectin.

PMID- 1371680
TI  - Different receptors mediate stimulation of nitric oxide-dependent cyclic GMP
      formation in neurons and astrocytes in culture.
AB  - The ability of various compounds to stimulate cyclic GMP accumulation was studied
      in neuronal and astrocyte-enriched primary cultures from rat cerebrum. Glutamate
      was the only agonist eliciting a response in neurons whereas several agonists had
      an effect in astrocytes but only those due to norepinephrine and glutamate were
      of considerable magnitude. The responses were markedly inhibited by the nitric
      oxide synthase inhibitor NG-monomethyl-L-arginine. The effect of glutamate
      appears to be mediated predominantly by NMDA receptors in neurons and by
      quisqualate AMPA-insensitive receptors in astrocytes.

PMID- 1371682
TI  - Occurrence of differentiated keratin peptide(K1) in cultured human squamous cell
      carcinomas.
AB  - To date, the largest keratin peptide(K1, 68 KD) has been absent in cultured human
      squamous cell carcinomas. Using a low salt aqueous solution, not containing high
      salt and Triton X-100, as a washing buffer for keratin extraction, followed by
      two dimensional polyacrylamide gel electrophoresis, immunological techniques and
      Northern blot analysis, we demonstrated K1 peptide in two kinds of cultured human
      squamous cell carcinomas. Until now keratin extraction has been done using high
      salt/Triton X-100 solution during which K1 peptide may be removed together
      developed an affinity with the buffer. Many investigators may have therefore
      overlooked K1.

PMID- 1371683
TI  - Cortisol secretion induced by substance P from bovine adrenocortical cells and
      its inhibition by calmodulin inhibitors.
AB  - When primary cultured bovine adrenocortical cells were treated with substance P
      (SP) at concentrations higher than 10 pM, cortisol output increased in a dose
      dependent fashion. Although other neurokinins, such as neurokinin A (NKA) and
      neurokinin B (NKB), were also effective in secreting cortisol, SP was the most
      potent among the tested neurokinins, the potency order being SP greater than NKA
      much greater than NKB. This suggests that the NK-1 type receptor on
      adrenocortical cells may be the site of action of SP on cortisol secretion. The
      maximal response in SP-induced cortisol secretion was comparable to that elicited
      by adrenocorticotropic hormone (ACTH). SP-induced cortisol secretion was
      dependent upon extracellular Ca2+ concentrations, and 45Ca2+ uptake into
      adrenocortical cells treated with SP was long-lasting. While, in the case of
      ACTH, 45Ca2+ uptake proceeded transiently, the increase in intracellular cAMP
      content was much greater compared with that of SP. Although KT-5720, an inhibitor
      of protein kinase A, inhibited potently ACTH-induced cortisol secretion, SP
      induced secretin was not affected by this inhibitor at all. On the other hand,
      calmodulin inhibitors, such as calmidazolium, trifluoperazine and N-(6
      aminohexyl)-5-chloro-1-naphthalenesulfonamide, were not more effective in
      inhibiting SP-induced cortisol secretion than secretion induced by ACTH. The
      present study indicates that SP may be one of the physiological stimulants of
      cortisol secretion and that an increase in intracellular Ca2+ concentration and
      the subsequent activation of calmodulin may precede SP-induced cortisol
      secretion.

PMID- 1371684
TI  - Nitric oxide but not prostacyclin is an autocrine endothelial mediator.
AB  - Using porcine aortic endothelial cells, the present study investigates whether
      stimulation of prostacyclin (PGI2) and nitric oxide also causes elevation of the
      respective second messengers cAMP and cGMP in the endothelial generator cells.
      The calcium ionophore A23187 at 0.3-3 microM increased endothelial cGMP levels up
      to 27-fold in an L-arginine-dependent manner as assessed through complete
      inhibition by NG-monomethyl-L-arginine (100 microM). The 36-fold PGI2 stimulation
      by 3 microM A23187 was not accompanied by an intracellular increase in cAMP or an
      enhanced cAMP efflux. Correspondingly, the PGI2 mimetic iloprost (10 pM-100
      microM) did not change endothelial cAMP levels. However, forskolin (1-100 microM)
      and prostaglandin E2 (PGE2) (0.1-10 microM) produced concentration-dependent
      increases in cAMP with a 9-fold and 8-fold stimulation at 100 microM forskolin
      and 10 microM PGE2, respectively. These results demonstrate that in contrast to
      NO, PGI2 acts as a strictly paracrine hormone without affecting the respective
      second messenger cAMP in the endothelial generator cells.

PMID- 1371685
TI  - Properties of redox-inactivated bleomycins. In vitro DNA damage and inhibition of
      Ehrlich cell proliferation.
AB  - Blenoxane, bleomycin A2, bleomycin B2, and demethyl bleomycin A2 and products of
      their reactions with Fe2+ and oxygen were used to explore the relationship
      between their capacity to carry out in vitro DNA strand scission and their growth
      inhibitory activity against Ehrlich cells. Reaction of Fe2+, bleomycin and O2 in
      the absence of DNA decreased the subsequent effectiveness of various bleomycin
      congeners to degrade DNA in the presence of Fe2+ and oxygen. In comparison with
      controls, this loss of strand scission activity was not paralleled by equivalent
      decreases in growth inhibition. Demethyl bleomycin A2 retained full biological
      activity relative to bleomycin A2, despite being only 30% as effective as
      bleomycin A2 in its ability to cleave DNA in vitro. Prior reaction of bleomycins
      with Fe2+ did not alter their capacity to reduce oxygen or affect their ability
      to generate the activated intermediate which, for native bleomycin structures, is
      competent to cleave DNA in vitro.

PMID- 1371686
TI  - Covalent binding of 14C- and 35S-labeled thiocarbamides in rat hepatic
      microsomes.
AB  - The covalent binding of a series of 14C- or 35S-labeled benzimidazole-2-thione
      (MBI) derivatives to rat liver microsomal proteins was studied to determine the
      mechanisms of hepatic monooxygenase oxidation of model anti-hyperthyroid
      compounds. All thiocarbamides tested (including methimazole) produced an NADPH
      dependent loss of cytochrome P450 (P450) chromophore which could be prevented by
      the addition of glutathione (GSH). The covalent binding of MBI to liver
      microsomal proteins from dexamethasone (DEX)-pretreated rats was enhanced 10-fold
      with NADPH, unaffected by P450 inactivation with 1-aminobenzotriazole (ABT) and
      attenuated by GSH addition. Heat treatment of microsomes to inactivate the flavin
      containing monooxygenase (FMO) decreased the observed binding. Equivalent amounts
      of [35S]- and [14C]MBI were covalently bound to hepatic microsomal proteins,
      suggesting retention of both the carbon and sulfur portions of the molecule in
      the MBI/protein adduct. Thiophilic reagents effected release of covalently bound
      [14C]- and [35S]MBI in equal amounts suggesting the presence of disulfide bonds
      between an MBI-derived sulfenic acid and microsomal protein thiols. Coincubation
      with bovine serum albumin (BSA) resulted in NADPH-dependent binding of [14C]-MBI
      to BSA sulfhydryls which was blocked by prior treatment of BSA with
      iodoacetamide. 1-Methyl-benzimidazole-2-thione (MMBI) also covalently bound to
      microsomal proteins and BSA but at levels lower than with MBI. P450, however,
      appeared to be more important than FMO in the metabolism of MMBI based on the
      effects of microsome heat pretreatment or ABT addition. In addition, ca. 1.5-fold
      more 35S- than 14C-label became bound. The covalent binding of [35S]1,3-dimethyl
      benzimidazole-2-thione (DMMBI) to microsomal proteins was ca. six times greater
      than that of [14C]DMMBI. ABT, catalase and superoxide dismutase had a minimal
      effect on [35S]DMMBI binding, while FMO inactivation decreased binding by ca.
      30%. These findings suggest that both monooxygenases contribute significantly to
      the hepatic metabolism of thiocarbamides. However, FMO activates thiocarbamides
      primarily to sulfenic acids, whereas P450 appears to produce both sulfenic acid
      and other reactive sulfur-derived metabolites. Thiol groups of P450 and other
      proteins are the molecular targets for these reactive species formed during the
      hepatic metabolism of anti-hyperthyroid drugs.

PMID- 1371687
TI  - Comparison of cyclosporine and FK506 effects on glutathione levels in rat
      cochlea, brain, liver and kidney.
AB  - Cyclosporine treatment (50 mg/kg/day, p.o.) caused increases in rat renal reduced
      glutathione (GSH) levels of 205 and 673%, respectively, after 5 and 10 days. No
      changes were seen in liver GSH with either dose of cyclosporine. FK506 (2.5
      mg/kg/day, p.o., for 7 days) caused an approximately 200% increase in kidney GSH,
      and an approximately 250% increase in hepatic GSH levels. Oxidized glutathione
      (GSSG) was never more than 1-2% of the level of the reduced form in any tissue
      from control animals. Small increases in the ratios of oxidized to reduced
      glutathione were seen in livers and kidneys from both cyclosporine- and FK506
      treated animals. No changes in GSH or GSSG levels were seen in brains or cochleas
      from any animal.

PMID- 1371688
TI  - Bleomycin regulation of transforming growth factor-beta mRNA in rat lung
      fibroblasts.
AB  - Pulmonary fibrosis is a well-known toxic response to bleomycin treatment. Here we
      demonstrate the direct effects of bleomycin on lung fibroblasts that resulted in
      a marked increase of collagen synthesis as compared with total noncollagen
      protein synthesis. Bleomycin treatment of rat lung fibroblast cultures resulted
      in an increase of total cellular transforming growth factor-beta (TGF-beta) mRNA
      and increased secretion of TGF-beta protein into the conditioned media. beta 2
      Microglobulin was measured as an mRNA that did not increase with bleomycin
      treatment. The bleomycin-induced increase of TGF-beta mRNA was decreased by cells
      cultured in the presence of either cycloheximide, an inhibitor of protein
      synthesis, or 2-mercapto-1-(beta-4-pyridethyl) benzimidazole, an inhibitor of RNA
      synthesis. To assess the mechanism underlying increased steady-state mRNA levels,
      the nuclear fraction was isolated from bleomycin-treated cells and the TGF-beta
      transcripts were determined. Transcription of TGF-beta mRNA was increased 12 h
      after bleomycin treatment, whereas the transcription of type I procollagen, type
      III procollagen, and beta-actin mRNAs were increased after 48 h of bleomycin
      treatment. beta 2-Microglobulin mRNA synthesis was not increased within this time
      frame. These results suggest bleomycin regulation of TGF-beta at both the mRNA
      and protein levels. Rats lung fibroblasts were separated by cell sorting into two
      subpopulations. One population of fibroblasts demonstrated increased procollagen
      type I mRNAs, whereas fibroblasts in the other population had increased
      procollagen type III mRNA. Following bleomycin treatment, TGF-beta mRNA was shown
      to be located more prominently in those fibroblasts that contain primarily
      collagen type I mRNAs.

PMID- 1371689
TI  - Alterations in DNA synthesis and cellular constituents in mouse lung following
      bleomycin injections.
AB  - Changes in the DNA synthesis and cellular constituents of mouse lung following
      repeated bleomycin (BLM) injections were studied. ICR mice were administered BLM
      subdermally for 10 days. Wet lung weight was increased 1.36 times on day 5 after
      the final administration compared with control mice receiving an identical volume
      of saline only for 10 days. The total number of cells in the bronchoalveolar
      lavage fluid of the BLM group reached a maximum on day 14, and histologic
      investigation of the lungs revealed marked cellular infiltrations. The labeling
      index obtained by the antibromodeoxyuridine monoclonal antibody method for cells
      was increased from days 5 to 14 in the BLM group. By day 28, these inflammatory
      changes had subsided and fibrotic remodeling had occurred. DNA polymerase
      activity in the lung tissue reached its maximal level on day 5 and remained
      unchanged until day 14. This phenomenon occurred in parallel with increases in
      DNA content and synthesis. During this period, an increase in DNA polymerase-beta
      activity and new induction of DNA polymerase-alpha activity were observed by
      phosphocellulose column chromatography. From these observations, it is concluded
      that: (1) repeated injections of BLM cause DNA injury in lung cells; (2) there is
      a subsequent increase in the DNA repair function as supported by the finding of
      an increase in DNA polymerase-beta activity; and (3) these lead further to cell
      proliferation as supported by the increase in both DNA polymerase-alpha activity
      and DNA content. Thus, a close relationship between morphologic changes and
      altered DNA synthesis was observed in the lungs of mice after BLM injections.

PMID- 1371690
TI  - HIV inhibitors targeted at the reverse transcriptase.
AB  - HIV inhibitors targeted at the virus-associated reverse transcriptase (RT) can be
      divided into two groups, depending on whether they are targeted at the substrate
      or nonsubstrate binding site. To the first group belong the 2',3'
      dideoxynucleosides (i.e., DDC, DDI), 3'-azido-2',3'-dideoxynucleosides (i.e.,
      AZT), 3'-fluoro-2',3'-dideoxynucleosides (i.e., FLT), 2',3'-didehydro-2',3'
      dideoxynucleosides (i.e., D4C, D4T) and carbocyclic derivatives thereof (i.e.,
      carbovir), 2'-fluoro-ara-2',3'-dideoxynucleosides, 1,3-dioxolane derivatives
      (i.e., 2',3'-dideoxyl-3'-thiacytidine), oxetanocin analogues and carbocyclic
      derivatives thereof (i.e., cyclobut-G) and the 9-(2
      phosphonylmethoxyethyl)adenine (PMEA) and 9-(3-fluoro-2
      phosphonylmethoxypropyl)adenine (FPMPA) derivatives. These compounds need to be
      phosphorylated intracellularly to their triphosphate forms before they act as
      competitive inhibitors or alternate substrates (chain terminators) of HIV RT. The
      second group includes the tetrahydro-imidazo[4,5,l-jk][1,4]-benzodiazepin
      2(1H)one (TIBO), 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine (HEPT),
      dipyrido[3,2-b:2',3'-e]-[1,4]diazepin-6-one (nevirapine) and pyridin-2(1H)one
      derivatives, which interact as such, noncompetitively, with a specific allosteric
      binding site of HIV-1 RT. Compounds belonging to the two different groups may
      give rise to synergism which combined, and, likewise, viral resistance to the
      compounds may arise through different mutations, depending on the nature of the
      compounds and the group to which they belong.

PMID- 1371691
TI  - Nonnucleoside inhibitors of HIV-1 reverse transcriptase: nevirapine as a
      prototype drug.
AB  - Nevirapine, a dipyridodiazepinone, is a highly specific inhibitor of HIV-1
      reverse transcriptase (RT) which exhibits an IC50 = 84nM in enzyme assays and
      IC50 = 40nM against HIV-1 replication in cell culture. This nonnucleoside
      inhibitor acts noncompetitively with respect to nucleoside triphosphates,
      template and primer suggesting that nevirapine does not bind to the active site
      of RT. Studies employing an azido analogue of nevirapine as a photoaffinity probe
      indicated that one molecule of inhibitor is sufficient to inactivate one molecule
      of heterodimeric enzyme and demonstrated that only the p66 subunit of p66/p51
      heterodimeric RT is covalently labeled by this probe. When subjected to trypic
      mapping, Tyr 181 and Tyr 188 were labeled with probe and consequently these
      aromatic residues are apparently near or actually within the RT binding site for
      nevirapine. The extent to which Tyr 181 and Tyr 188 participate/contribute to
      nevirapine binding was determined by making amino acid substitutions at these
      positions using the corresponding residues from HIV-2 RT which is not sensitive
      to nevirapine. A change at either position dramatically decreased the enzymes'
      sensitivity to nevirapine, as well as to TIBO derivative and Merck L-693,593,
      indicating that both Tyr 181 and 188 are crucial for inhibitor-enzyme
      interaction. Cell culture selection in the continued presence of nevirapine
      results in the appearance of resistant HIV-1, Tyr 181 to Cys, raising the concern
      that combination drug therapy will be required in the clinic.

PMID- 1371692
TI  - Interferons in the persistence, pathogenesis, and treatment of HIV infection.
AB  - Interferon (IFN) plays an important role in the treatment and pathogenesis of HIV
      disease. Recent studies show beneficial effects of IFN alpha in the treatment of
      HIV-associated Kaposi's Sarcoma and early HIV-infection. Moreover, cell culture
      studies support these beneficial effects. HIV infection of monocytes is blocked
      by IFN alpha administered at the time of viral challenge. The IFN alpha-treated
      cells show no evidence of HIV infection. Viral gene products produced in
      monocytes infected with HIV then treated with IFN alpha gradually decrease to
      baseline. Large quantities of proviral DNA are seen in the HIV-infected IFN alpha
      treated cells with little evidence for viral transcription suggesting true
      microbiological latency. While most viral infections of cells result in IFN
      production, HIV is a notable exception. Indeed, HIV does not induce monocytes to
      produce IFN alpha and blocks its production following poly(I).poly(c)
      stimulation. This allows HIV yet another mechanism to evade an important host
      antiviral response. Paradoxically, the appearance of IFN activity in sera of HIV
      infected patients is associated with disease progression, not resolution. Recent
      observations showing that the interaction between HIV-infected monocytes and PBMC
      results in the production of IFN alpha s with reduced anti-HIV activity may help
      explain this paradox. Thus, IFN alpha plays an important but complex role in HIV
      disease. The elucidation of cellular factors that regulate the antiretroviral
      effects of IFN alpha may lead to the development of novel therapeutic strategies
      for HIV infection.

PMID- 1371693
TI  - An antigenic structure of the trans-activator protein encoded by human T-cell
      leukemia virus type-I (HTLV-I), as defined by a panel of monoclonal antibodies.
AB  - In order to study an antigenic structure of the trans-activator protein encoded
      by human T-cell leukemia virus type-I (HTLV-I), tax1 antigen, we generated and
      characterized a panel of rat anti-tax1 monoclonal antibodies (MAbs) designated
      WATM-1, WATM-2, WATM-3, and WATM-4. These MAbs were derived from WKA rats
      immunized with HTLV-I-transformed (HTLV-I+) syngeneic T cells. Immunoblot assays
      showed that: (1) All the MAbs reacted with the tax1 antigen in HTLV-I+ cell lines
      and a recombinant tax1 antigen, PX141 (containing entire tax1 polypeptide); (2)
      WATM-3 and WATM-4, but not WATM-1 or WATM-2, reacted with a truncated tax1
      antigen, XD59 (tax1 amino acids 180-338); (3) None of them reacted with another
      truncated tax1 antigen, XD128 (tax1 amino acids 1-47 and 286-353); and (4) each
      of the four MAbs had different reactivity with tax1-related antigens in the range
      38-41 kDa expressed in simian cell lines infected with various HTLV-I-related
      simian retroviruses (STLV-I). None of the MAbs reacted with HTLV-II tax antigen.
      Human sera containing anti-tax1 antibodies interfered specifically with the
      antigen-specific binding of all the MAbs. These results suggest that the present
      rat MAbs are directed against various epitopes on the tax1 antigen. An antigenic
      structure of the tax1 antigen deduced from reactivity of a panel of anti-tax1
      MAbs including the present rat MAbs is discussed.

PMID- 1371694
TI  - Identification of distinct epitopes of endoglin, an RGD-containing glycoprotein
      of endothelial cells, leukemic cells, and syncytiotrophoblasts.
AB  - Endoglin is a glycoprotein expressed predominantly on human endothelial cells. It
      was first identified with mAb 44G4, produced against the pre-B acute
      lymphoblastic HOON cell line. We now report that four mAbs independently produced
      against human umbilical vein endothelial cells (HUVECs), chronic myelogenous
      leukemia in blast crisis, or U-937 pro-monocytic cells stimulated with phorbol
      myristate acetate also react with endoglin. High levels of reactivity of all mAbs
      were observed with HUVEC, while intermediate levels were seen with HOON and U-937
      cells. By sequential immunoprecipitation from HUVEC and U-937 cell extracts, it
      was established that RMAC8, HEC-19, 8E11, and 1G2 mAbs react with the same
      protein as 44G4. Three distinct epitopes recognized by 44G4, RMAC8, and 1G2 mAbs
      were identified by competitive radioimmunoassay and flow cytometry. The HEC-19
      epitope is spatially related to the 44G4 epitope, whereas the 8E11 epitope is
      most closely related to the 1G2 epitope. Western blot analysis showed that all
      antibodies react with the endoglin dimer (Mr = 170,000) purified from placenta.
      Immunostaining of sections of full-term placenta revealed reactivity not only
      with fetal vessels but also with the syncytiotrophoblast, the fetal cell layer
      which interfaces with maternal blood. When HUVEC monolayers were treated with the
      different mAbs to endoglin, prior to incubation with U-937 cells, a 5- to 10-fold
      stimulation of adhesion was observed. A fibronectin hexapeptide containing RGD,
      but not the corresponding RGE peptide, was capable of inhibiting the increased
      adhesion, when tested with mAb 44G4 and RMAC8. However, the same peptides had no
      effect on the binding of any of the five anti-endoglin mAbs to cells. Since 44G4
      and RMAC8 recognize two distinct epitopes of endoglin, and since all five mAbs
      stimulated adhesion, the results suggest that a signal has been triggered through
      endoglin on HUVECs. Endoglin might be implicated either directly, by binding to a
      specific integrin-like ligand, or indirectly, by regulating the level of adhesion
      between certain integrins and their receptors.

PMID- 1371695
TI  - Purification and patch clamp analysis of a 40-pS channel from rat liver
      mitochondria.
AB  - Patch clamp analysis of membranes reconstituted with a fraction isolated from
      detergent-solubilized mitochondrial membranes by affinity chromatography on
      immobilized quinine earlier indicated the presence of two classes of ion
      channels, of about 40- and 140-pS conductance in medium including 150 mM KCl. Now
      a 57-kDa constituent of the quinine-affinity column eluate has been identified as
      the 40-pS channel. Protein fractions derived from the quinine-affinity column
      eluate by preparative isoelectric focusing with a Rotofor cell have been
      reconstituted into phospholipid vesicle membranes by detergent dialysis, and
      vesicles have been enlarged for patch clamping by dehydration and rehydration.
      Voltage clamp analysis has been carried out on excised patches bathed
      symmetrically in buffered medium containing 150 mM KCl and 100 microM CaCl2.
      Patches of membrane incorporating the 57-kDa protein exhibit 40-pS conductance
      transitions. The magnitude of conductance transitions is similar when Na+
      replaces K+ in the bathing medium, indicating little selectivity of the 40-pS
      channel for K+ relative to Na+. Another fraction derived from the quinine
      affinity column eluate is found to contain the larger channel, now estimated to
      have an average conductance of about 130 pS. Patches of control membrane prepared
      in the same way but without protein exhibit no channel activity.

PMID- 1371696
TI  - cDNA cloning and sequencing of rat alpha 1-macroglobulin.
AB  - cDNA clones coding for the plasma protease inhibitor alpha 1-macroglobulin were
      isolated from a rat liver library. The obtained cDNA sequence contained 4701
      nucleotides and had an open reading frame coding for a 1,500 amino acid long
      protein, including a 24 amino acid signal peptide. The identity of the deduced
      protein sequence as alpha 1-macroglobulin was established by comparison with
      published peptide sequences of the protein. The mature protein shares 53% and 57%
      overall amino acid identity with the two other identified members of the rat
      alpha-macroglobulin family, alpha 1-inhibitor 3 and alpha 2-macroglobulin. A
      sequence typical for an internal thiol ester was identified. Of the 24 cysteines,
      23 are conserved with alpha 2-macroglobulin. However, instead of the two most C
      terminal cysteines in alpha 2-macroglobulin, which forms a disulfide bridge in
      the receptor binding domain, alpha 1-macroglobulin contains phenylalanine. One
      mRNA species hybridizing with the alpha 1-macroglobulin probe was observed in rat
      and mouse liver RNA (approximately 6.2 kb), whereas no corresponding transcript
      was detected in RNA from human liver.

PMID- 1371697
TI  - Solubilization and molecular characterization of active galanin receptors from
      rat brain.
AB  - Galanin receptors were solubilized from rat brain using the zwitterionic
      detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS).
      Binding of 125I-galanin to the soluble fraction was time- and temperature
      dependent, saturable, and reversible. Scatchard analysis of binding data
      indicated that the soluble extract contained a single class of galanin binding
      sites with a Kd of 0.8 nM and a Bmax of 26 fmol/mg of protein. Unlabeled galanin
      and its fragments galanin(2-29) and galanin(1-15) antagonized the binding of 125I
      galanin to CHAPS-solubilized extracts with relative potencies similar to those
      observed with membrane receptors. Galanin(3-29) was found inactive. Binding of
      125I-galanin to CHAPS extracts was inhibited by guanine nucleotides with the
      following rank order of potency: GMP-P-(NH)P greater than GTP greater than GDP.
      Molecular analysis of the soluble galanin receptor by covalent cross-linking of
      125I-galanin to CHAPS extracts using disuccinimidyl tartrate and further
      identification on SDS-PAGE indicated that the soluble galanin binding site
      behaves as a protein of Mr 54,000. After incubation of CHAPS extracts with 125I
      galanin, gel filtration on Sephacryl S-300 followed by ultracentrifugation on
      sucrose density gradient revealed a binding component with the following
      hydrodynamic parameters: Stokes radius, 5 nm; s20,w, 4.5 S; Mr, 98,000;
      frictional ratio, 1.6. GMP-P(NH)P treatment of CHAPS extracts gave rise to a
      molecular form with the following characteristics: Stokes radius, 4 nm; s20,w,
      3.3 S; Mr, 57,000; frictional ratio, 1.4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371698
TI  - A rapamycin-selective 25-kDa immunophilin.
AB  - FKBP25, a previously uncharacterized 25-kDa FK506- and rapamycin-binding protein,
      was purified to homogeneity from calf thymus, brain, and spleen, and the sequence
      of a 215 amino acid (aa) 24-kDa C-terminal peptide was established. The N
      terminal domain (101 aa) is unrelated to any known protein, is hydrophilic, and
      is predicted by circular dichroism spectroscopy to be largely alpha-helix. The C
      terminal domain (114 aa) is homologous to FKBP12 and other FKBPs but has a
      potential nuclear targeting sequence and a unique insertion of seven amino acids
      in one of its loops. FKBP25 displays the rotamase activity characteristic of
      FKBPs; the activity is inhibited by the immunosuppressants rapamycin (Ki = 0.9
      nM) and FK506 (Ki = 160 nM), but not cyclosporin A. The protein, its rapamycin
      selectivity, and the potential nuclear targeting sequence are discussed in terms
      of the structure of hFKBP12.

PMID- 1371700
TI  - Density separation of human red blood cells on self forming Percoll gradients:
      correlation with cell age.
AB  - Human red blood cells were density separated on self-forming Percoll gradients.
      Redistribution of density fractionated red blood cells was studied by
      recentrifugation on self-forming Percoll gradients. A protocol that avoids
      centrifugation of red cells prior to removal of white cells and introduces EDTA
      before red cell pelleting completely avoided redistribution. Dense red cells
      separated according to this method were senescent on the basis of a biochemical
      and a physical criterion: the increase in the band 4.1a:4.1b ratio (Mueller, T.,
      Jackson, C.W., Dockter, M.E. and Morrison, M. (1987) J. Clin. Invest. 79, 492
      499) and the loss of maximum deformability. Characterization also included the
      relative content of two surface proteins (complement receptor 1, CR1 (Ripoche, J.
      and Sim, R.B. (1986) Biochem. J. 235, 815-821); decay accelerating factor, DAF)
      on density fractionated red cells. Unlike cytoplasmic proteins, these proteins
      face similar conditions, whether located on circulating reticulocytes or aging
      red cells. Both components were lost linearly within experimental errors with
      cell density and were lower by 60 and 40% in dense than light cells,
      respectively.

PMID- 1371699
TI  - Unilateral lung transplantation: ultrastructural studies of ischemia-reperfusion
      injury and repair in the canine pulmonary vasculature.
AB  - The left lung was transplanted in 12 adult beagles; the donor lung had been
      preserved by flush perfusion of the pulmonary artery with 60 ml/kg of Euro
      Collins solution at 4 degrees C then stored in Euro-Collins solution at 4 degrees
      C for 6 hours. Biopsy specimens were taken from control and donor left lungs
      before and immediately after perfusion, after 6 hours storage, and after
      transplantation at 4 and 24 hours (total = 46). Tissue from seven animals was
      injected with the tracer ruthenium red. All tissue was examined by light and
      electron microscopy. After preservation capillary edema developed, but ruthenium
      red did not penetrate junction complexes, indicating structurally intact
      complexes. The proportion of ruthenium red-labeled plasmalemmal vesicles
      decreased (p less than 0.05). Endothelial cells and type I pneumonocytes because
      abnormally thin and detached from the basement membrane. The epithelial, but not
      the endothelial, sheet was disrupted. Four hours after transplantation, edema
      decreased, and endothelial and epithelial cells regained a more normal shape. The
      proportion of labeled plasmalemmal vesicles increased (p less than 0.05) by 24
      hours, when the value was similar to normal. During preservation, edema formed
      when alveolar capillary white cell count was normal and decreased after
      reperfusion when the cells increased threefold (p less than 0.001), indicating
      that edema was not neutrophil dependent. Many small muscular arteries constricted
      intensely on cold perfusion. Four hours after transplantation, these
      abnormalities had improved. CONCLUSION: The pulmonary vasculature showed no
      evidence that it had sustained additional structural injury after reperfusion.
      Reperfusion was associated with a gradual resolution of the structural
      abnormalities incurred during preservation.

PMID- 1371701
TI  - Human HuH-7 hepatoma cells express urokinase and plasminogen activator inhibitor
      1: identification, characterization and regulation by inflammatory mediators.
AB  - The human hepatoma HuH-7 cell line was shown to constitutively express both a
      plasminogen activator (PA) and a plasminogen activator inhibitor (PAI). Four
      sublines of the HuH-7 cell line were analyzed and found to express differing
      amounts of both PA and PAI. The plasminogen activator produced by these cells was
      identified as urokinase based upon molecular weight, inhibition of activity with
      anti-UK but not anti-t-PA antibodies, adherence to an anti-UK affinity column and
      by Northern blotting demonstrating positive hybridization with the cDNA for UK,
      but not with the t-PA cDNA. The inhibitor produced by HuH-7 cells was identified
      as PAI-1 by molecular weight, immunoblotting techniques, adherence to an anti-PAI
      1 affinity column, and by Northern blotting demonstrating positive hybridization
      with the cDNA for PAI-1, but not with the PAI-2 cDNA. The expression of both UK
      and PAI-1 by HuH-7 cells could be modulated by cytokines known to influence the
      acute phase response. The addition of interleukin-1 (IL-1) induced the expression
      of both UK and PAI-1. The increase of PAI-1 was due to an increase in amount of
      the PAI-1 mRNA. The presence of both interleukin-6 (IL-6) and tumor necrosis
      factor alpha (TNF) also increased UK and PAI-1 levels, although not as
      dramatically as IL-1. The addition of IL-1 together with IL-6 produced a slight
      synergistic response with respect to PAI-1 expression. This suggests that PAI-1
      is able to respond to mediators which aid in the induction of the acute phase
      response. These studies demonstrate that cells of liver origin are able to
      produce components of the fibrinolytic system. The synthesis of these components
      can be altered by inflammatory mediators and thus may be involved in hepatic
      regulation of fibrinolysis in both normal and diseased states.

PMID- 1371702
TI  - A flow cytometric study of the effect of heat on the kinetics of cell
      proliferation of Chinese hamster V-79 cells.
AB  - Two methods involving labelling cells with bromodeoxyuridine (BrdUrd) have been
      used to study by flow cytometry the effect of hyperthermia (43 degrees C for up
      to 1 h) on Chinese hamster V79 cells. One method involved the use of an antibody
      to BrdUrd after pulse-labelling the cells either before or at time intervals
      after treatment. In the second method, the cells were incubated continuously in
      BrdUrd after heat treatment, and the components of the cell cycle were then
      visualized by staining with a combination of a bis-benzimidazole and ethidium
      bromide. All three methods showed that heating at 43 degrees C stopped DNA
      synthesis which, at 37 degrees C, subsequently recovered reaching the normal rate
      8-12 h later. The cells in S phase at the time of treatment then progressed to G2
      where they were further delayed. Cells heated in G1. after the recommencement of
      synthesis, progressed around the cycle, albeit slower than in unheated cells. The
      difference between the cells in G1 and S phases at the time of treatment may
      account for the greater sensitivity of S phase cells to hyperthermia.

PMID- 1371703
TI  - On the supramolecular organization of gramicidin channels. The elementary
      conducting unit is a dimer.
AB  - The question, whether the conducting channels formed by the linear gramicidins
      are dimers (as is generally believed) or tetramers (as has been recently proposed
      [Stark G., M. Strassle, and Z. Takacz. 1986. J. Membr. Biol. 89:23-37; Strassle,
      M., G. Stark, M. Wilhelm, P. Daumas, F. Heitz, and R. Lazaro. 1989. Biochim.
      Biophys. Acta. 980:305-314]) has been addressed in single-channel experiments.
      The experimental approach was based on the ability of electrophysiological
      (single-channel) experiments to resolve the number of hybrid channel types that
      could form between gramicidin A or C and O-pyromellityl-gramicidin A or C (in
      which a pyromellitic acid residue has been esterified to the ethanolamine-OH
      group [Apell, H.-J., E. Bamberg, H. Alpes, and P. Lauger. 1977. J. Membr. Biol.
      31:171-188]). The presence of the bulky, negatively charged pyromellityl group at
      the channel entrances endows the hybrid channels with characteristically
      different features and thus facilitates the resolution of the different hybrid
      channel types. Only two hybrid channel types were detected, indicating that the
      conducting channels are membrane-spanning dimers. There was likewise no evidence
      for lateral association between conducting channels and nonconducting monomers.
      These results can be reconciled with those of Stark et al. (op. cit.) if
      gramicidin channel formation involves a (slow) folding into beta 6.3-helical
      monomers followed by the dimerization step.

PMID- 1371704
TI  - Multichannel recordings from membranes which contain gap junctions.
AB  - We have studied multichannel patch-clamp recordings in earthworm axon septal
      membranes that contain gap junctions. Though all channels have the same
      conductance and selectivity, the probabilities of the conductance levels in the
      majority of the recordings could not be fit by assuming independent and identical
      channels; in these cases, we found that at least two different open probabilities
      were required to explain the data. The data thus suggest that, within one
      junctional membrane complex, there exists a heterogenous channel population of
      similar but not identical channel types. The analysis also revealed cases where
      cooperativity between individual channels was the only explanation for the
      amplitude histograms of the observed multichannel activity. The conclusions drawn
      are based on a theoretical analysis of multichannel current-amplitude histograms.
      We derive two tests for independent and identical channels. We analyze the
      effects of mode shifting. These results are based on the ratio of peaks in the
      histograms; they are independent of the number of channels in the patch and the
      model of channel gating. In some cases failure to fulfill the criteria of these
      tests implied an interdependence or cooperativity between channels. Lastly, we
      have devised statistical tests for stability of the recording in the presence of
      variance due to finite sample size.

PMID- 1371705
TI  - Electrostatic coupling of ion pumps.
AB  - In this paper the electrostatic interactions between membrane-embedded ion-pumps
      and their consequences for the kinetics of pump-mediated transport processes have
      been examined. We show that the time course of an intrinsically monomolecular
      transport reaction can become distinctly nonexponential, if the reaction is
      associated with charge translocation and takes place in an aggregate of pump
      molecules. First we consider the electrostatic coupling of a single dimer of ion
      pumps embedded in the membrane. Then we apply the treatment to the kinetic
      analysis of light-driven proton transport by bacteriorhodopsin which forms two
      dimensional hexagonal lattices. Finally, for the case of nonordered molecules, we
      also consider a model in which the pumps are randomly distributed over the nodes
      of a lattice. Here the average distance is equal to that deduced experimentally
      and the elemental size of the lattice is the effective diameter of one single
      pump. This latter model is applied to an aggregate of membrane-embedded Na, K-
      and Ca-pumps. In all these cases the electrostatic potential considered is the
      exact solution calculated from the method of electrical images for a plane
      membrane of finite thickness immersed in an infinite aqueous solution
      environment. The distributions of charges (ions or charged binding sites) are
      considered homogeneous or discrete in the membrane and/or in the external
      solution. In the case of discrete distributions we compare the results from a
      mean field approximation and a stochastic simulation.

PMID- 1371706
TI  - Re-irradiation of soft-tissue sarcoma.
AB  - Re-irradiation for local recurrence of malignancy after radical radiotherapy is
      of proven benefit at head and neck sites but has seldom been used elsewhere. This
      paper reports a series of 10 patients re-irradiated with external-beam techniques
      for local recurrence of soft-tissue sarcoma of the limb and limb girdle following
      initial limb conserving management with surgery and radiotherapy (dose range 33
      60 Gy). Median survival was 14 months following re-treatment. Two cases received
      treatment with high-energy electrons and the rest with megavoltage photons. Five
      patients re-treated with radical intent (dose range 40-60 Gy) had a median
      survival of 36 months and median recurrence-free survival of 16 months. All five
      patients treated palliatively (dose range 12-50 Gy) have died, although two
      demonstrated local control until death. Acute reactions were not severe.
      Radionecrosis was seen in one patient who was re-irradiated twice (total dose 145
      Gy) and subsequently required amputation. One other case required amputation for
      persistent local disease, but in the remaining eight, limb conservation was
      achieved. Re-irradiation of soft-tissue offers good local control and may avoid
      amputation.

PMID- 1371707
TI  - Subchronic methamphetamine treatment enhances ouabain-induced striatal dopamine
      efflux in vivo.
AB  - The effect of manipulation of the Na+ gradient between the intracellular and
      extracellular media on striatal dopamine (DA) efflux under steady-state
      conditions after subchronic methamphetamine (MAP) treatment was investigated.
      Rats were injected with 4 mg/kg MAP or saline (i.p.), once daily for 14 days.
      Seven days after the last injection, ouabain (10(-4) M), a selective inhibitor of
      the Na+,K(+)-ATPase, was infused locally through a semi-permeable probe in the
      striatum. Ouabain induced a significantly greater (P less than 0.01) increase of
      the DA concentrations in the striatal perfusate in the subchronic MAP than the
      control group. The levels of 3,4-dihydroxyphenylacetic acid (DOPAC) (P less than
      0.05) and 5-hydroxyindoleacetic acid (5-HIAA) (P less than 0.05) were
      significantly higher in the subchronic MAP than in the control group. Reserpine
      pretreatment (5 mg/kg, i.p.) did not affect the enhanced ouabain-induced DA
      efflux (P less than 0.01) in the subchronic MAP group, and the levels of DOPAC (P
      less than 0.01), 5-HIAA (P less than 0.01) and HVA (P less than 0.01) were also
      significantly higher in the subchronic MAP than in the control group. In
      contrast, alpha-methyl-p-tyrosine (250 mg/kg, i.p.) pretreatment abolished the
      ouabain-induced efflux of DA, DOPAC and HVA, but not 5-HIAA, in both groups.
      Specific striatal [3H]ouabain binding and striatal Na+,K(+)-ATPase activity in
      the subchronic MAP and control groups did not differ significantly. These results
      suggest that subchronic MAP treatment facilitates the efflux of newly synthesized
      DA, which is induced by the ouabain-induced decrease of the Na+ gradient between
      intracellular and extracellular media.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371708
TI  - Cholecystokinin induces c-fos expression in hypothalamic oxytocinergic neurons
      projecting to the dorsal vagal complex.
AB  - Systemic administration of cholecystokinin (CCK) decreases gastric motility and
      stimulates pituitary secretion of oxytocin (OT). Although peripheral OT does not
      affect gastric function, increasing evidence suggests that central OT secretion
      acting within the dorsal vagal complex (DVC) can alter gastric motility. To
      evaluate whether systemically administered CCK is capable of activating
      oxytocinergic neurons projecting to the DVC, we utilized fluorogold retrograde
      labeling from the DVC in combination with c-fos and OT immunocytochemical
      staining to quantitatively analyze paraventricular nucleus (PVN) neurons of rats
      following injection of CCK at a dose known to cause maximal pituitary OT
      secretion (100 micrograms/kg i.p.). Our results showed that 2320 +/- 63 PVN
      neurons were retrogradely labeled from the DVC; 146 +/- 21 (6.3%) of these
      contained OT, and these cells were predominantly located in the medial
      parvocellular subdivision of the PVN. Of all retrogradely labeled cells, 671 +/-
      112 (28.9%) expressed c-fos after CCK stimulation, and 68 +/- 14 of these (10.1%)
      contained OT. Approximately 50% of the OT-containing neurons retrogradely labeled
      from the DVC stained positively for c-fos. Many magnocellular OT neurons in the
      PVN that were not retrogradely labeled from the DVC also expressed c-fos after
      CCK stimulation. These results demonstrate that parvocellular OT neurons
      projecting to the DVC are co-activated along with magnocellular OT neurons
      projecting to the pituitary following administration of a large dose of CCK, and
      lend support to a possible functional role for OT as a central neurotransmitter
      that modulates vagal efferent traffic to the gastrointestinal tract.

PMID- 1371709
TI  - Effect of neonatal capsaicin treatment on cholecystokinin-(CCK8) satiety and
      axonal transport of CCK binding sites in the rat vagus nerve.
AB  - Cholecystokinin (CCK) binding sites which accumulate at ligatures placed on the
      rat vagus nerve may mediate the satiety actions of CCK. Treatment of neonatal
      rats with capsaicin attenuated the satiety effect of injected CCK in adult life.
      Capsaicin pretreatment also reduced, but did not eliminate, the accumulation of
      CCK binding sites proximal and distal to ligatures on either cervical trunk. A
      similar effect was observed following ligation of subdiaphragmatic vagal trunks.
      The CCK receptor antagonists, MK-329 and L-365,260, inhibited binding to
      capsaicin- and vehicle-treated nerves to a similar degree. Densities of CCK
      binding sites in the nucleus tractus solitarius and area postrema were also
      markedly affected by neonatal capsaicin treatment.

PMID- 1371710
TI  - Convergence of subthalamic and striatal efferents at pallidal level in primates:
      an anterograde double-labeling study with biocytin and PHA-L.
AB  - Small injections of two highly sensitive anterograde tracers, Phaseolus vulgaris
      leucoagglutinin (PHA-L) and biocytin, into the striatum and the subthalamic
      nucleus of squirrel monkeys (Saimiri sciureus) have revealed a high degree of
      convergence of striatal and subthalamic fibers upon single pallidal cells. Both
      afferent systems formed highly complex band-like patterns that were largely in
      register with one another. At single cell level, the somata of pallidal neurons
      were closely surrounded by subthalamic terminal varicosities, whereas the
      dendrites were entwined mostly by striatal fibers. Typically, a
      subthalamopallidal fiber coursed in a caudorostral direction and arborized
      according to a uniform pattern along its trajectory in the pallidum. Numerous
      thin and markedly varicose axon collaterals detached themselves at right angle
      from the main subthalamopallidal fiber. These highly branched collaterals were
      mostly oriented along the mediolateral plane and entwined rather loosely the
      dendrites but surrounded very closely the somata of pallidal neurons. In
      contrast, a striatopallidal fiber travelled in a rostrocaudal direction. Its
      initial segment made only en passant contacts with pallidal cell bodies, whereas
      its distal end closely entwined the dendrites of pallidal neurons, forming
      arrangements similar to 'woolly' type fibers. These results suggest that a single
      subthalamic fiber may influence a rather large collection of pallidal neurons in
      a similar fashion, compared to the striatal input which appears to exert a more
      specific control upon selected sets of the same pallidal neurons.

PMID- 1371711
TI  - The fibroma-like variant of epithelioid sarcoma. A fibrohistiocytic/myoid cell
      lesion often confused with benign and malignant spindle cell tumors.
AB  - Five cases of a previously undescribed variant of epithelioid sarcoma are
      presented. This variant differs from the usual lesion in its absence of the
      typical necrobiotic nodular epithelioid pattern. It is instead composed of
      deceptively bland fibrohistiocytic and myoid cells arranged in a fibroma-like or
      dermatofibroma-like pattern with an affinity for osseous involvement. The
      clinical presentation, ultrastructural features, and presence of vimentin and low
      molecular weight keratin within the tumor cells justifies their designation as an
      epithelioid sarcoma variant.

PMID- 1371712
TI  - Combined assessment of vascular and myometrial invasion as a model to predict
      prognosis in stage I endometrioid adenocarcinoma of the uterine corpus.
AB  - The prognostic significance of vascular invasion as compared with other
      pathologic features was evaluated in 102 cases of endometrioid adenocarcinoma
      confined to the uterus (Stage I) treated by hysterectomy. By univariate analysis,
      survival most closely correlated with patient age, architectural grade, depth of
      myometrial invasion, vascular invasion, and the presence of perivascular
      lymphocytic infiltrates. Among these, vascular invasion and the presence of
      perivascular lymphocytic infiltrates were the best indicators of prognosis. In
      contrast to perivascular lymphocytic infiltrates, the presence of a lymphocytic
      infiltrate at the tumor-myometrial junction was not related to outcome. The
      presence of vascular invasion was found to be associated closely with
      perivascular lymphocytic infiltrates. These two features may be related
      biologically and were designated "vascular invasion-associated changes." By
      multivariate analysis with the Cox proportional hazards model, the depth of
      myometrial invasion and the presence of vascular invasion-associated changes were
      found to provide a highly reliable model for predicting outcome. The highly
      predictive value of vascular invasion as a prognostic factor in Stage I
      endometrial carcinoma suggests that it is the mechanism by which occult
      metastasis develops in patients whose disease progresses after hysterectomy. It
      is likely that other variables correlating with recurrence, such as the presence
      of deep myometrial invasion and high tumor grade, may act by increasing the
      probability of vascular invasion and subsequent metastasis.

PMID- 1371713
TI  - Tumor cell dissemination triggers an intrathecal immune response in neoplastic
      meningitis.
AB  - The intrathecal immune response in neoplastic meningitis (NM) was studied by
      quantitation of immune parameters such as immunoglobulin G (IgG); IgM;
      interleukins (IL) 1, 2, 4, and 6; soluble IL-2 receptors (sIL-2R); interferon
      gamma (IFNy); tumor necrosis factor-alpha (TNF alpha); and three tumor markers,
      carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and fibronectin (FN), in
      47 paired cerebrospinal fluid (CSF) and serum samples from patients with NM from
      different carcinomas, malignant melanoma, and lymphoma. Elevated IgG and IgM
      indices, CSF oligoclonal Ig bands, and CSF IL-6 indicated an intrathecal immune
      activation in most patients with NM. Results for IL-1, IL-2, and IL-4 were always
      negative. sIL-2R and IFNy were detected occasionally but not associated with
      specific malignant neoplasms. CSF TNF alpha was detected only in NM from cases of
      malignant melanoma. None of the immune parameters proved useful for the
      differentiation of NM from autoimmune or inflammatory conditions. Immune
      parameters were not correlated with tumor markers CEA, AFP, or FN. Results for
      AFP were positive only in a case of glioblastoma. CEA was a useful and specific
      diagnostic parameter in carcinomatous NM. CSF FN levels frequently were elevated
      but are not specific for NM.

PMID- 1371714
TI  - Angiogenic effects of macrophages isolated from ascitic fluid aspirated from
      women with advanced ovarian cancer.
AB  - The cellular components of ascitic fluid aspirated from the peritoneal cavity of
      women with advanced ovarian cancer were separated on a Ficoll gradient. Isolated
      macrophages, which were further purified, elaborated a growth factor which was
      mitogenic for human endothelial cells isolated from umbilical veins, arteries and
      the omental microvasculature in vitro, and was angiogenic in vivo. It is
      postulated that the macrophage-derived factor enhances tumor neovascularization
      of the widespread ovarian-derived peritoneal malignant lesions appearing in these
      patients, thus contributing to their rapid growth and metastasis, and the poor
      prognosis of the disease.

PMID- 1371715
TI  - Mechanisms of natural resistance to antifolates in human soft tissue sarcomas.
AB  - Efforts to use fresh human sarcoma cells for evaluating antifolate resistance
      with an in situ thymidylate synthesis assay using 5-[3H] deoxyuridine were
      unsuccessful because of low thymidylate synthesis activity in enzymatically
      disaggregated tumors. By incubating tumor cell suspensions in supplemented RPMI
      1640 medium with 10% fetal bovine serum for 3 days, activity of the in situ
      thymidylate synthesis assay markedly increased (1.42 versus 0.03 pmol/h/10(7)
      cells), thus allowing 75% of samples to be evaluated for antifolate sensitivity.
      By criteria developed with a methotrexate-resistant and -sensitive cell line,
      this assay indicated that most sarcomas are naturally resistant to methotrexate
      (12 of 15). Natural resistance to 10-ethyl-10-deazaaminopterin and trimetrexate
      was also observed in 60% of the samples (nine of 15, respectively). The results
      from the 3-day in situ assay were confirmed by specific tests for resistance
      mechanisms in most sarcoma samples. The resistance mechanisms detected were
      impaired polyglutamylation, an increased level of dihydrofolate reductase, and
      amplification of this gene. These results encourage further exploration of this
      assay to predict response to antifolates in individual patients and to evaluate
      efficacy of new antifolates as candidates for clinical trial.

PMID- 1371716
TI  - Elevated expression of pp60c-src in low grade human bladder carcinoma.
AB  - The results presented in this report demonstrate that the tyrosine-specific
      protein kinase activity of pp60c-src is elevated over that recorded in normal
      bladder mucosa in a subset of human bladder carcinomas. Increased kinase activity
      was observed mainly in low grade bladder lesions and was associated, at least in
      part, with elevated levels of pp60c-src expression. Extension of this analysis to
      a panel of human bladder carcinoma cell lines confirmed previous observations of
      low pp60c-src kinase activity in three lines established from high grade (GIII)
      bladder tumors and revealed increased kinase activity in three alternative
      bladder lines derived from GI or GII tumors. Use of an anti-phosphotyrosine
      antibody in Western blot analysis revealed the presence of novel phosphotyrosyl
      cellular substrates in human bladder cell lines and tumors displaying elevated
      pp60c-src kinase activity. These observations suggest an association for the src
      protooncogene in urothelial cell differentiation events.

PMID- 1371718
TI  - Serum prostate specific antigen levels in mice bearing human prostate LNCaP
      tumors are determined by tumor volume and endocrine and growth factors.
AB  - The ability of prostate-specific antigen (PSA) to predict tumor volume and stage
      in patients with prostate cancer would be improved if factors regulating its
      production and clearance were better defined. A thorough understanding of the
      pharmacokinetics (regulation of production, metabolism, and excretion) of PSA has
      been precluded, however, by the absence of an in vivo animal model. The purposes
      of this study are to develop a murine model for evaluating PSA pharmacokinetics
      in vivo and to assess factors that influence PSA production in vitro. The human
      prostate cancer cell line, LNCaP, was chosen because it is androgen sensitive and
      PSA positive. Although LNCaP cells are usually nontumorigenic when inoculated
      s.c. in athymic mice, coinoculation of 1 x 10(6) LNCaP cells with 1 x 10(6) human
      bone fibroblasts reliably produces PSA-secreting carcinomas. This LNCaP model
      provides accurate correlation between tumor volume and serum PSA levels (r =
      0.94) and demonstrates that tumor volume and androgens are codeterminants of
      circulating PSA levels. Following castration, serum PSA levels decrease rapidly
      up to 8-fold and increase up to 20-fold following androgen supplementation,
      without detectable castration-induced tumor cell death or concomitant changes in
      tumor volume. Serum PSA levels increase 0.24 ng/ml/mm3 of tumor, which is
      approximately 5-fold less than that estimated for humans. Most likely this
      reduced PSA index (PSA:tumor volume ratio) results from a 7-fold faster clearance
      of PSA in athymic mice than in humans; other than this shorter half-life, PSA
      elimination in the murine model appears similar to that in humans, with both
      following first-order kinetics characteristic of a two-compartment model.
      Interestingly, following prolonged growth (greater than 21 days) in castrate
      hosts, LNCaP tumors are capable of adapting to an androgen-deprived environment
      whereby LNCaP tumors regain the ability to secrete PSA in amounts similar to the
      precastrate state. In LNCaP cells, androgens increase PSA mRNA levels 4-fold in
      vivo and in vitro. PSA mRNA expression is also altered by various growth factors.
      Changes in PSA production induced by androgens and growth factors do not always
      parallel changes in LNCaP cell growth rate induced by these factors, suggesting
      that PSA production occurs independently of cell growth rate and may be
      influenced by various interrelated factors, including hormonal and stromal
      milieu. Observations from this murine model suggest that androgens and tumor
      volume are independent determinants of serum PSA levels and imply that decreases
      in circulating PSA following antiandrogen therapy may not always reflect a
      corresponding reduction in tumor volume.

PMID- 1371717
TI  - Tumor-promoting phorbol ester down-regulates the androgen induction of prostate
      specific antigen in a human prostatic adenocarcinoma cell line.
AB  - Prostate-specific antigen (PSA) is the most sensitive marker available for
      monitoring the progression of prostate cancer and response to therapy. In a
      previous study, we demonstrated tissue-specific expression of PSA glycoprotein
      and mRNA and its regulation through the androgen receptor. In this study, we
      examine the effects of protein kinase A (PKA) and protein kinase C (PKC) on the
      androgen regulation of PSA in a human adenocarcinoma cell line, LNCaP. Northern
      blot analysis demonstrated that forskolin, an activator of PKA, had no effect on
      the androgen regulation of PSA. However, the phorbol ester 12-O-tetradecanoyl
      phorbol-13-acetate (TPA), a direct activator of PKC, showed a time- and dose
      dependent repression of the androgen regulation of PSA glycoprotein and mRNA. The
      biologically inactive phorbol ester, 4 alpha-phorbol-12,13-didecanoate, had no
      effect. Staurosporine, a PKC inhibitor, blocked the TPA-mediated repression of
      the androgenic stimulation of PSA glycoprotein. In addition, the calcium
      ionophore, A23187, was able to simulate the actions of TPA, presumably through
      activation of PKC via calcium mobilization. In summary, the androgenic regulation
      of PSA protein and mRNA is repressed by tumor-promoting phorbol esters through
      the PKC pathway. This indicates that the effects of TPA may be secondary to
      repressed gene transcription or altered mRNA stability. In addition, this study
      emphasizes that the androgenic regulation of PSA is complex and may involve other
      extracellular transduction signals.

PMID- 1371719
TI  - Induction of T-cell-mediated immunity against MethA fibrosarcoma by intratumoral
      injections of a bacillus Calmette-Guerin nucleic acid fraction.
AB  - MY-1, which consists of DNA and RNA extracted and purified from bacillus Calmette
      Guerin (BCG), has been shown to have strong antitumor activity against various
      experimental tumors. To examine the role of T cells in the antitumor mechanism of
      MY-1, the effect of MY-1 injection on the development of tumor-specific immunity
      against MethA fibrosarcoma was investigated. MY-1 injections inhibited tumor
      growth less effectively in T-cell-deficient nude mice than in normal BALB/c mice.
      MethA tumor growth was suppressed after inoculation with L3T4-positive
      lymphocytes from tumor-bearing mice treated with MY-1. MethA-specific delayed
      type hypersensitivity was also detected in tumor-bearing mice treated with MY-1.
      Immunohistochemical analyses showed that many L3T4-positive and a few Lyt2
      positive cells infiltrated the regressing tumors. These results indicate that
      intratumoral MY-1 injections induce a MethA-specific, L3T4-positive cell
      mediated, delayed-type hypersensitivity, which is necessary for the tumor
      regression.

PMID- 1371721
TI  - Mechanisms of activated Ca2+ entry in the rat pancreatoma cell line, AR4-2J.
AB  - The characteristics of Ca2+ entry activated by surface receptor agonists and
      membrane depolarization were studied in the rat pancreatoma cell line, AR4-2J.
      Ca2+ mobilization activated by substance P, bombesin, or muscarinic receptor
      stimulation was found to involve both Ca2+ release and entry. In addition,
      depolarization of the surface membrane of AR4-2J cells with elevated
      concentrations of K+ activated Ca2+ entry. Ca2+ entry induced by membrane
      depolarization was inhibited by the L-channel antagonist, nimodipine, while that
      due to surface receptor agonists was not inhibited by this agent. The microsomal
      Ca(2+)-ATPase inhibitor, thapsigargin, caused both depletion of the agonist
      sensitive intracellular Ca2+ pool and sustained Ca2+ influx indistinguishable
      from that produced by bombesin or methacholine. These results confirm that,
      unlike the pancreatic acinar cells from which they are presumably derived, AR4-2J
      cells express voltage-sensitive, dihydropyridine-inhibitable Ca2+ channels.
      However, in contrast to previous reports with this cell line, in the AR4-2J cells
      in use in our laboratory, and under our experimental conditions, surface receptor
      agonists (including substance P) do not cause Ca2+ influx through voltage
      sensitive Ca2+ channels. Instead, we conclude that agonist-activated Ca2+
      mobilization is initiated by (1,4,5)IP3-mediated intracellular Ca2+ release and
      that Ca2+ influx is regulated primarily, if not exclusively, by the state of
      depletion of the (1,4,5)IP3-sensitive intracellular Ca2+ pool.

PMID- 1371720
TI  - Allogeneic tumor-specific cytotoxic T lymphocytes.
AB  - We report the development of cytotoxic T lymphocytes specific for an allogeneic
      brain tumor in a rat model. DA strain cytotoxic T cell precursors stimulated by
      an allogeneic tumor (9L gliosarcoma) from the Fischer rat could generate a
      population of cytotoxic T lymphocytes that lysed the allogeneic 9L tumor but
      failed to lyse other targets, including Fischer concanavalin-A(ConA)-stimulated
      lymphoid blast targets. DA T cells depleted of reactivity to the Fischer
      haplotype (DA-F) retained reactivity to the 9L tumor, demonstrating that T cell
      precursors with specificity for normal Fischer alloantigens were not required for
      the generation of a response to the 9L Fischer tumor. The preferential lysis of
      the tumor target did not simply reflect a higher density of Fischer target
      antigens on the tumor than that found on normal Fischer ConA blast targets.
      First, the relative densities of class I antigen on the 9L tumor and normal
      Fischer ConA blasts were comparable. Second, cytotoxic T cells could not be
      generated from DA-F precursors when Fischer ConA blasts were used as stimulators.
      If DA-F T cells were simply responding to the higher density of Fischer antigen
      found on 9L tumor, it would have been expected that the ConA blasts expressing
      comparable levels of antigen to that found on the tumor would have generated
      cytotoxicity for both the 9L and ConA targets. We conclude that the cytotoxic T
      cells are specific for a determinant expressed only by the tumor. Such tumor
      specific cytotoxic T cells could be useful in vivo for adoptive immunotherapy of
      brain tumors.

PMID- 1371722
TI  - Discordant results in human chorionic gonadotropin assays.
AB  - Discordance has been reported in human chorionic gonadotropin (hCG)
      concentrations measured by different immunoassay kits. We examined the results
      for 40 serum samples assayed with 10 different hCG immunoassay kits. Results
      varied considerably. Individual sample results varied by as much as 58-fold.
      Average results for different kits varied by as much as 1.4-fold for pregnancy
      (20 samples) and 2.2-fold for trophoblast disease (20 samples) serum. We
      investigated the causes of this discordance. hCG or hCG beta are general names
      for mixtures of hCG, hCG alpha, or hCG beta immunoreactive molecules in serum.
      These mixtures include regular hCG, nicked hCG (missing peptide linkages at beta
      44-45 or beta 47-48), carbohydrate variants of hCG, hCG missing the beta-subunit
      C-terminal segment, free beta-subunit, beta-core fragment, and free alpha
      subunit. We prepared standards for each of these major variants and measured
      their reactivities in the 10 hCG immunoassay kits. Free beta-subunit reactivity
      varied from nonrecognition (anti-beta:anti-alpha type kits; Hybritech Tandem-R
      and others) to overrecognition (one kit had five-fold greater affinity for free
      beta than for hCG). Kits with antibodies to beta-subunit C-terminal segment
      (Organon NML and others) failed to recognize hCG missing this segment, a
      component of serum hCG in trophoblast disease. Kits with anti-hCG antibodies
      (Serono MAIA-clone and others) had minimal recognition of nicked hCG (12%), a
      component of all serum hCG samples, and consistently gave the lowest values with
      all serum samples. We conclude that differences in recognition of nicked hCG,
      free beta, and these other hCG variants cause discordance in hCG immunoassay
      results.

PMID- 1371723
TI  - Ratio of serum tartrate-inhibitable acid phosphatase to total serum protein in
      benign prostatic hypertrophy and prostatic carcinoma.
AB  - The activity concentration and the specific activity (the ratio of enzyme
      activity to total serum protein) of the tartrate-inhibitable fraction of acid
      phosphatase [orthophosphoric monoester phosphohydrolase (acid optimum), EC
      3.1.3.2; TIAP] were related to benign prostatic hypertrophy and to prostatic
      carcinoma. As expected, the TIAP activity concentrations assayed in the sera of
      patients with benign prostatic hypertrophy were within the range of those assayed
      in normal human sera. In contrast, the specific activities of TIAP determined in
      the sera of patients with benign prostatic hypertrophy were significantly higher
      than those determined in the control group. In the sera of prostatic carcinoma
      patients, both the TIAP activity concentrations and the TIAP specific activities
      differed significantly (F = 730) from the normal values.

PMID- 1371724
TI  - Modified immunoradiometric assay of parathyroid hormone-related protein: clinical
      application in the differential diagnosis of hypercalcemia.
AB  - We have developed a sensitive, specific solid-phase immunoradiometric assay
      (IRMA) of parathyroid hormone-related protein (PTH-RP) with use of affinity
      purified polyclonal immunoglobulins. Antibodies recognizing PTH-RP(37-74) are
      immobilized to a polystyrene bead to "capture" analytes from the sample;
      antibodies to epitopes within the 1-36 amino acid region of PTH-RP are labeled
      with 125I. This IRMA recognizes PTH-RP(1-74) and PTH-RP(1-86) equivalently, but
      does not detect N-terminal or C-terminal fragments of PTH-RP, intact human
      parathyrin (PTH), or fragments of PTH. PTH-RP is not stable in plasma at 3-5
      degrees C or room temperature, but a mixture of aprotinin (500 kallikrein
      units/L) and leupeptin (2.5 mg/L) improves PTH-RP stability in blood samples. In
      plasma collected in the presence of these protease inhibitors from normal
      volunteers and patients with various disorders of calcium metabolism, PTH-RP
      concentrations were above normal (greater than 1.5 pmol/L) in 91% (42 of 46) of
      patients with hypercalcemia associated with nonhematological malignancy. In
      plasma from patients with other hypercalcemic conditions (e.g., primary
      hyperparathyroidism, sarcoidosis, and vitamin D excess), PTH-RP was undetectable.
      Above-normal concentrations of PTH-RP and total calcium decreased to normal in a
      patient with an ovarian cyst adenocarcinoma after surgical removal of the tumor.
      We conclude that PTH-RP is related to and probably the causative agent of
      hypercalcemia in most patients with cancer, and that measurements of PTH-RP are
      useful in the diagnosis and management of patients with tumor-associated
      hypercalcemia.

PMID- 1371725
TI  - Increased plasma amylase in the family of a patient with 3-hydroxy-3
      methylglutaryl-coenzyme A lyase deficiency.
AB  - A patient with 3-hydroxy-3-methylglutaryl-CoA lyase (HMG-CoA lyase, EC 4.1.3.4)
      deficiency presented consistently above-normal values of plasma amylase (EC
      3.2.1.1). Activities measured were in the lower normal range in family members
      not proven heterozygotes and in the upper normal range in the proven
      heterozygotes. Heterozygosity was proven by intermediate HMG-CoA lyase activities
      determined in cultured fibroblasts and in lymphocytes in the parents and the
      paternal grandmother. Because all of the family members had diseases of the
      pancreas, colon, and liver, we question whether the heterozygote state
      contributes to the impaired function of these organs. Our findings of
      significantly increased amylase activities in the heterozygotes and the patient,
      in comparison with the other family members, support this hypothesis.

PMID- 1371726
TI  - Hemoglobin variants.

PMID- 1371727
TI  - Cross-reactivity of the B/B' subunit of the Sm ribonucleoprotein autoantigen with
      proline-rich polypeptides.
AB  - Using recombinant fusion proteins representing different regions of the human Sm
      B/B' polypeptide, the 4B4 monoclonal anti-Sm antibody was found to bind a C
      terminus epitope that is proline-rich. 4B4 cross-reacted with the p24 gag protein
      of HIV-1 and with other polypeptides rich in proline residues, including
      collagen. BALB/c mice immunized with human collagen not only produced antibodies
      to the immunizing antigen but also antibodies to Sm. This immune mouse serum also
      recognized C-terminus B/B' fusion proteins. These data suggest that the Sm B/B'
      antigen contains a poly-Pro epitope that is shared by several autoantigens and
      retroviral proteins. These sites may be important in the induction of
      autoantibodies through molecular mimicry.

PMID- 1371728
TI  - In situ hybridization of interleukin-1 in CD14-positive cells in rheumatoid
      arthritis.
AB  - Interleukin 1 (IL-1) has been implicated as an inflammatory mediator in
      rheumatoid arthritis (RA). Many cell types, including macrophages, lymphocytes,
      fibroblasts, and endothelial cells, can produce IL-1 and it is known that IL-1
      production is under transcriptional control. It has, however, been difficult to
      define in vivo the predominant cellular source of this mediator in RA. Here, we
      have used the combination of in situ hybridization of mRNA and cellular
      immunophenotyping with monoclonal antibodies to show that the IL-1 beta gene is
      expressed predominantly by CD14-positive macrophages in synovial tissue from
      patients with RA. Synovial macrophages were also associated with the
      immunoreactive IL-1 peptide. These cells appear to be the major source of IL-1
      beta within the rheumatoid synovium in vivo and must be regarded as playing a
      central role in the chronic inflammation and joint destruction of RA.

PMID- 1371729
TI  - Essential fatty acids and iron are involved at distinct stages of the
      proliferative cycle but not in the activation of human T cells.
AB  - In the absence of serum, optimal lymphocyte proliferation is obtained when
      cultures are supplemented with transferrin and an essential fatty acid (EFA). In
      order to study the effects of iron in conjunction with EFA on T-cell
      proliferation, we have utilized a chemically defined serum-free culture system to
      achieve better control of the variables involved. This system includes three
      different serum-free media (SFM) that differ in total iron content and source of
      iron: (i) transferrin-free medium containing a high concentration (500 microns)
      of a soluble iron salt in the form of ferric citrate (Fe-SFM); (ii) iron
      saturated human transferrin (5 micrograms/ml) (T-SFM); and (iii) iron-free medium
      (SFM(-Fe)) without any apparent source of iron. None of these SFM supported
      proliferation of T cells stimulated by the combination of phorbol 12,13
      dibutyrate/ionomycin or phytohemagglutinin. Restoration of the proliferative
      response was only observed following supplementation of the iron-containing media
      with linoleic acid (complexed to bovine serum albumin (LA/BSA)). In cultures
      containing LA/BSA, the addition of iron alone in the absence of transferrin (Fe
      SFM) resulted in similar responses to the transferrin-containing medium (T-SFM).
      Low levels of RNA synthesis in mitogen-stimulated T cells could be demonstrated
      in the presence or absence of iron and the addition of LA/BSA resulted in marked
      enhancement of RNA synthesis, regardless of the availability of iron. Cell cycle
      analysis showed that 91-94% of the cells cultured in SFM were arrested in G0/G1.
      These cells could progress through the cell cycle following the addition of
      LA/BSA, but only in the iron-containing media. Unlike DNA or RNA synthesis,
      activation of T cells could be demonstrated in SFM with or without iron as shown
      by the normal induction of c-fos and early growth response gene mRNA, normal
      expression of IL2 and transferrin receptors, and normal IL2 production, despite
      the arrest of cells in G0/G1. These results suggest that although human T-cell
      growth is iron and EFA dependent, the early events of T-cell activation are both
      iron and EFA independent.

PMID- 1371730
TI  - An immunosuppressant compound, FK-506, prevents the progression of autoimmune
      myocarditis in rats.
AB  - A new immunosuppressive compound, FK-506, is a macrolide produced by Streptomyces
      tsukubaensis. It is reported that FK-506 prolongs the viability of allogenic
      grafts of the heart and kidney in vivo and inhibits the development of autoimmune
      diseases. Furthermore, immunosuppressive therapy of myocarditis in humans has
      been given special attention by various observers; however, it is controversial.
      This study investigates the effects of FK-506 on experimental autoimmune
      myocarditis in rats. We performed two experiments. In Experiment 1, FK-506 was
      given intramuscularly on Days 11-20 after the first immunization. The rats were
      immunized twice (on Day 0 and Day 7). They were injected subcutaneously in the
      footpads with 1.0 mg of human cardiac myosin in equal volumes of complete
      Freund's adjuvant supplemented with Mycobacterium tuberculosis. They were divided
      into four groups: Control (six rats, saline), group 1 (six rats, FK-506: 0.1
      mg/kg/day), group 2 (seven rats, FK-506: 0.32 mg/kg/day), and group 3 (six rats,
      FK-506: 1.0 mg/kg/day). To investigate the histologic extent of myocarditis, we
      formulated a histologic score (0-3). Histologic scores were: Control, 1.90 +/-
      0.14; group 1, 0.97 +/- 0.46; group 2, 0.03 +/- 0.05; and group 3, 0 +/- 0. The
      indices of heart weight/body weight were: Control, 0.74 +/- 0.10%; group 1, 0.45
      +/- 0.05%; group 2, 0.35 +/- 0.03%; and group 3, 0.35 +/- 0.03%. In Experiment 2,
      FK-506 was given on Days 1-10 after the first immunization, earlier than in
      Experiment 1. The rats were similarly divided into four groups. Each group was
      given the same dose of FK-506 as in Experiment 1. Histologic scores were: Control
      1.49 +/- 0.24; group 1, 1.60 +/- 0.22; group 2, 0.29 +/- 0.41; and group 3, 0.03
      +/- 0.03. The indices of heart weight/body weight were: Control, 0.69 +/- 0.15%;
      group 1, 0.76 +/- 0.09%; group 2, 0.42 +/- 0.08%; and group 3, 0.37 +/- 0.03%.
      Accordingly, in Experiments 1 and 2, the effects of FK-506 on autoimmune
      myocarditis were dose-dependent. On the other hand, in Experiments 1 and 2, not
      only in the control group but also in all treated groups, the titers of anti
      myosin IgG were high. In conclusion, even if it is administered just before the
      onset of myocarditis, FK-506 is extremely effective at suppressing autoimmune
      myocarditis, despite a high titer of anti-myosin IgG.

PMID- 1371731
TI  - Effects of methotrexate on rat liver regeneration after partial hepatectomy.
AB  - 1. Methotrexate was administered immediately after partial (70%) hepatectomy,
      resulting in complete inhibition of dihydrofolate reductase in 24 h-regenerating
      liver. 2. At 48 h and 72 h after partial hepatectomy, thymidylate synthase
      activity was increased, whereas thymidine kinase was inhibited, by the injection
      of methotrexate. The DNA and RNA contents and the liver weight were also reduced
      in methotrexate-treated rats. 3. The immunoblotting assay showed that
      methotrexate stimulated the synthesis of thymidylate synthase protein in 48 h
      regenerating liver. At the same time, thymidylate synthase activity was directly
      inhibited by methotrexate. The mechanisms of inhibition of these enzymes by
      methotrexate appeared to be different.

PMID- 1371733
TI  - Expression and probable roles of cell adhesion molecules in lung inflammation.

PMID- 1371732
TI  - Development of airway epithelium. Patterns of expression for markers of
      differentiation.

PMID- 1371734
TI  - Mastoparan, via a GTP binding protein, activates apical chloride and potassium
      conductances, decreases cell volume, and increases permeability of cultured
      epithelial cell monolayers.

PMID- 1371735
TI  - Preparation of isolated surface membranes from cystic fibrosis airway epithelial
      cells.

PMID- 1371736
TI  - Cellular-neural-cellular pathways mediating the response of tracheal ciliary beat
      frequency (CBFt) to inhaled capsaicin.

PMID- 1371737
TI  - Molecular biology of islet amyloid polypeptide.
AB  - We investigated the relationship between non-insulin-dependent diabetes mellitus
      (NIDDM) and islet amyloid polypeptide (IAPP) gene by restriction fragment length
      polymorphism (RFLP) and polymerase chain reaction (PCR)-direct sequencing
      analysis. Endonuclease BglII and/or PvuII RFLP analysis revealed no positive
      correlation of IAPP gene with NIDDM. In PCR-direct sequencing of 25 NIDDM
      patients, no nucleotide sequence differences were found. These data do not
      support the view that IAPP plays an important role in the pathogenesis of NIDDM.
      cDNAs encoding cat, rat, mouse, guinea pig and degu IAPP precursors were also
      cloned, and comparison of these predicted amino acid sequences clarified the
      species difference, especially between amyloid-forming and non-amyloid-forming
      species. Amino acid residues 25-28 of mature IAPP might be responsible for their
      amyloidogeneity. The alternative splicing transcripts of guinea pig IAPP gene
      were identified by using PCR. If these types of transcripts are translated, N
      terminal mutated IAPP might be produced and act as an antagonist. The signal
      peptide cleavage site of rat IAPP precursor was also identified by an in vitro
      translation and processing system.

PMID- 1371738
TI  - Noninvasive mapping of muscle representations in human motor cortex.
AB  - We used transcranial magnetic stimulation to map the cortical representations of
      4 upper extremity muscles (abductor pollicis brevis, flexor carpi radialis,
      biceps, and deltoid) of 10 normal subjects. Three stimuli were delivered to scalp
      positions 1 cm apart, and the amplitude and latency of the motor evoked
      potentials (MEPs) were averaged for each position. Maps were described in terms
      of number of excitable scalp positions, amplitude of MEPs, scalp positions for
      evoking largest amplitude MEPs, and threshold for producing MEPs. We compared
      different muscles across subjects and the same muscles on the left and right
      sides in individual subjects. Distal muscles had larger representations with
      higher amplitude MEPs and lower thresholds. Biceps and deltoid on the left had
      larger representations and higher MEP amplitudes than on the right. Maps showed a
      somatotopic progression on the scalp of proximal to distal muscles along a
      posteromedial to anterolateral axis.

PMID- 1371739
TI  - Magnetic brain stimulation with a double coil: the importance of coil
      orientation.
AB  - The human motor cortex can be excited by currents induced by a transient magnetic
      field generated in a coil over the scalp. A 9 cm mean diameter circular coil
      centered at the vertex is optimally placed for exciting the hand area.
      Anticlockwise current flow in the coil preferentially excites the left hemisphere
      and vice versa. A double coil has been used to investigate the orientation of
      inducing currents at which activation of cortical neural elements is maximal. The
      inducing current flowed in the same direction in the central segment of the coil
      and followed a monophasic wave form. The coil was rotated through 360 degrees
      over the motor area in increments of 45 degrees and compound muscle action
      potentials from the first dorsal interosseous muscle were recorded. The largest
      responses were obtained with the coil at about 50 degrees to the parasagittal
      plane with a backward flowing inducing current. The optimal angle did not depend
      on stimulus intensity or background voluntary contraction. This orientation
      corresponds to an maximal induced current flowing forwards approximately at right
      angles to the central sulcus. It is postulated that horizontal neural elements
      are aligned in this direction and are preferentially excited by these monophasic
      magnetic stimuli. The results have important implications for mapping the motor
      areas with magnetic stimulators.

PMID- 1371740
TI  - Relevance of stimulus duration for activation of motor and sensory fibers:
      implications for the study of H-reflexes and magnetic stimulation.
AB  - Electric stimuli with durations of 0.5-1.0 msec are optimal for studies of H
      reflexes. It is more difficult to obtain H-reflexes with shorter duration stimuli
      or with magnetic stimulation. In order to understand this behavior, we studied
      the excitation thresholds for motor and sensory fibers in the ulnar, median and
      tibial nerves using both electric and magnetic stimulation. For short duration
      electrical stimuli (0.1 msec) the threshold for motor fibers is lower than for
      sensory fibers. For longer duration electric stimuli (1.0 msec) the threshold for
      sensory fibers is lower. For magnetic stimulation the threshold for motor fibers
      is much lower than for sensory fibers. Thus, stimulus duration is a critical
      parameter for sensory fiber excitation, and current magnetic stimulators are not
      optimal.

PMID- 1371741
TI  - Jitter measurement by axonal micro-stimulation. Guidelines and technical notes.
AB  - Single fiber EMG (SFEMG) with axonal micro-stimulation is a convenient method to
      study the neuromuscular jitter at the individual motor end-plates. Compared to
      the original method of jitter measurement in voluntarily activated muscle, it has
      the advantage of perfect control of the discharge rate, including pauses in
      activity, useful in quantitative estimation of the neuromuscular transmission
      defect. It obviates the need to search for muscle fiber pairs. It can be used in
      young children and in uncooperative patients, as well as those with impaired
      voluntary motor control. It is useful in animal experiments as well as veterinary
      medicine. The technique eliminates the possibility of overestimating the jitter
      due to unrecognized interdischarge interval dependent jitter, as well as that of
      underestimating it due to unrecognized low jitter in split muscle fibers. The
      technique has certain pitfalls causing under- or overestimation. The paper gives
      practical guidelines and hints as to how to avoid some of these, particularly
      errors due to overlooked threshold stimulation and to unrecognized direct muscle
      fiber stimulation.

PMID- 1371742
TI  - Motor evoked potentials: a new method of controlled facilitation using
      quantitative surface EMG.
AB  - A new method of assessing MEP facilitation using surface EMG under computer
      control is described. Transcranial magnetic stimulation with voluntary
      contraction at a value between 2 and 6% of maximal surface EMG activity produced
      responses with shortest latencies and largest amplitudes and power. No
      significant changes occurred when facilitation increased beyond this level. These
      results are similar to previously published studies using a force transducer,
      confirming the reliability of the system as an alternative method of monitoring
      voluntary contraction. The controlling system may potentially provide an easy,
      flexible, quantitative method of ensuring adequate, reproducible facilitation
      with minimum EMG interference for testing in a clinical setting.

PMID- 1371743
TI  - Normal conduction in pathways traversing an asymptomatic multiple sclerosis
      plaque.
AB  - A 31-year-old woman developed right facial myokymia as the initial manifestation
      of multiple sclerosis (MS). An MRI scan revealed a focal signal abnormality
      confined to the left dorsolateral pontomedullary region. Brain-stem auditory
      evoked potentials (BAEPs), somatosensory evoked potentials (SEPs), and blink
      reflex (BR) failed to show a conduction abnormality through the left brain-stem
      lesion. Instead, BAEP and BR indicated a conduction defect in the right pons and
      EMG showed myokymic discharges in right facial muscles. Our findings provide rare
      documentation of normal conduction through a presumably asymptomatic MS plaque.
      The abnormal MRI signal likely represents tissue edema, rather than
      demyelination. This case demonstrates that physical findings in MS patients may
      correlate better with electrophysiological abnormalities than with MRI
      abnormalities.

PMID- 1371744
TI  - Effects of fatigue on the stretch reflex in a human muscle.
AB  - The effects of fatigue on the electromyographic (EMG) reflex activities were
      compared during sustained voluntary contractions and contractions evoked by
      electrical stimulation (30 Hz) in the human first dorsal interosseus (FDI). Short
      latency (SL), medium latency (ML) and long latency (LL) reflex responses to a
      ramp-and-hold stretch of the muscle were recorded and analysed in 27 healthy
      subjects of both sexes. The amplitude of the reflex components was normalized as
      function of the amplitude of the surface action potential (SAP) recorded in
      response to the supramaximal stimulation of the motor nerve. The results indicate
      that for a similar reduction of force, SL and ML are significantly reduced after
      fatigue induced by voluntary contractions but they are not when the fatigue test
      is performed by electrical stimulation at the motor point. In voluntary fatigue
      experiments, the LL component showed no significant decrease below control
      values, but an enhancement was observed during electrically evoked contraction.
      This enhancement remained above control values for at least 15 min during the
      recovery period, whereas SL and ML decreases returned to control within 5 min
      after the fatigue tests. The electrical stimulation applied to the skin overlying
      the FDI at an intensity lower than the motor threshold did not affect SL and ML,
      but enhanced LL for about 15 min. On the contrary, the anaesthesia of the skin
      overlying the FDI induced a decrease in LL without significant change of SL and
      ML. It is concluded that muscle reflex fatigue is present during sustained
      voluntary contractions and decreases SL and ML responses to quick
      stretches.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371745
TI  - Physiological analysis of motor reorganization following lower limb amputation.
AB  - It is now known that amputation results in reorganization of central motor
      pathways, but the mechanism for the changes is unclear. One possibility is
      alteration of the excitability of the alpha motoneurons. We studied motor
      reorganization and excitability of alpha motoneurons to Ia input in 6 subjects
      with unilateral lower limb amputation. A Cadwell MES-10 stimulator was used to
      deliver transcranial magnetic stimuli through a circular coil centered on the
      sagittal axis 4 cm anterior to Cz and through an 8-shaped coil positioned over
      scalp locations 1 cm apart along the coronal axis. Surface EMG was recorded
      bilaterally from quadriceps femoris, the first muscle immediately proximal to the
      site of amputation. Excitability of the spinal alpha motoneuron pool to Ia
      afferents was assessed by determining the ratio of the maximal H reflex to the
      maximal M response (H/M ratio) elicited in the quadriceps femoris. Stimuli of
      equal intensity delivered to optimal scalp positions recruited a larger
      percentage of the alpha motoneuron pool in muscles ipsilateral to the stump than
      in those contralateral to the stump (P less than 0.01). Mean onset latencies of
      motor evoked potentials were shorter in ipsilateral muscles than in contralateral
      muscles (P less than 0.01). Muscles ipsilateral to the stump showed a trend
      toward activation from a larger number of scalp positions than those
      contralateral to the stump (P = 0.06). There was no difference in the quadriceps
      H/M ratios (7.2% ipsilateral vs. 10.9% contralateral). The absence of changes in
      the excitability of the alpha motoneuron pool in the presence of motor
      reorganization targeting muscles proximal to the stump suggests that
      reorganization occurs proximal to the alpha motoneuron level.

PMID- 1371746
TI  - The effects of cooling supplementary motor area and midline cerebral cortex on
      neuronal responses in area 4 of monkeys.
AB  - It has been postulated that the supplementary motor area (SMA) is involved in the
      initiation of movement and in gating of afferent input to motor cortex (MI) from
      peripheral receptors. We studied the responses of 119 neurons in MI to imposed
      disturbances of wrist-movement performance generated by the introduction of
      torque pulses before, during and after localized cooling of the SMA in conscious
      monkeys. The cooling of SMA did not prevent monkeys from making these simple
      movements. Eighty-two neurons responded to the wrist perturbations. Only 7 of
      these neurons changed their responsiveness with unilateral or bilateral cooling
      of SMA. From the data we have obtained on MI neuronal firing patterns, the SMA
      does not appear to modulate the long-latency trans-cortical stretch reflex during
      the periods in a task that we have investigated. Nor does it prevent animals from
      performing these simple movements to a visual target.

PMID- 1371747
TI  - Slow positive dorsal cord potentials activated by heterosegmental stimuli.
AB  - Heterosegmental slow positive waves (HSPs) and segmental spinal cord potentials
      were recorded from the cord dorsum in ketamine-anesthetized rats. Forepaw
      stimulation produced HSPs in the lumbo-sacral enlargement (lumbar HSPs), whereas
      hind paw stimulation evoked HSPs in the cervical cord (cervical HSP). Both the
      HSP and the secondary component of the slow positive wave (P2s) in the segmental
      spinal cord potential were highly vulnerable to anesthetics and completely
      disappeared after spinal cord transection at the C1/2 level, indicating that both
      the HSP and P2s are produced by a long feedback loop via supraspinal structures.
      The lumbar HSP evoked by forepaw stimulation was maximal in amplitude at the L5
      level and more dominant in the ipsilateral cord dorsum than in the contralateral
      one, but widely distributed in the lumbo-sacral cord. A variability of onset (7
      18 msec for cervical and 5-17 msec for lumbar HSPs) and peak (22-35 msec for
      cervical and 12-50 msec for lumbar HSPs) suggests the existence of several nuclei
      to form the feedback loops for descending impulses to produce the HSPs. There
      were no peak latency differences between the HSPs and P2s. Since there were
      several similar characteristics between the P2s and HSP such as a high
      vulnerability to anesthetic, a complete disappearance after high spinal
      transection and similar response curves to graded intensities of stimulation,
      there may be a close relationship between their feedback nuclei and the pathways
      mediating them. All wide dynamic range (WDR) neurons (12/12) in lamina V of Rexed
      responded to heterosegmental stimulation with inhibition of firing.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1371748
TI  - Topographic mapping of the human motor cortex with magnetic stimulation: factors
      affecting accuracy and reproducibility.
AB  - We recorded motor evoked potentials (MEPs) from deltoid, biceps brachii, abductor
      pollicis brevis and flexor carpi radialis muscles of 5 normal volunteers during
      transcranial magnetic stimulation. With the subjects at rest, an 8-shaped
      magnetic coil was used to deliver 30 stimuli to different scalp positions 0.5 or
      1.0 cm apart. The variability in amplitude and latency of MEPs was studied as a
      function of the scalp position stimulated, the number of stimuli at each
      position, and the percentage of maximal peripheral M responses (%M) elicited. The
      results were used to estimate the optimal number of stimuli at each position and
      the optimal spacing of scalp positions for topographic mapping of the human motor
      cortex. The amplitude and latency variability of MEPs were higher when suboptimal
      scalp positions were stimulated. Consequently, a larger number of stimuli were
      required to determine representative MEP amplitudes at suboptimal positions. In
      addition, there was an inverse relationship between %M recruited by transcranial
      magnetic stimuli in different subjects and the variability in MEP amplitude and
      latency. Latency variability was less pronounced than amplitude variability.
      Optimal sampling conditions are required to produce the best topographic maps,
      particularly to show subtle reorganization patterns in the human motor cortex.

PMID- 1371749
TI  - Cloning and expression of a human ATP-citrate lyase cDNA.
AB  - A full-length cDNA clone of 4.3 kb encoding the human ATP-citrate lyase enzyme
      has been isolated by screening a human cDNA library with the recently isolated
      rat ATP-citrate lyase cDNA clone [Elshourbagy et al. (1990) J. Biol. Chem. 265,
      1430]. Nucleic-acid sequence data indicate that the cDNA contains the complete
      coding region for the enzyme, which is 1105 amino acids in length with a
      calculated molecular mass of 121,419 Da. Comparison of the human and rat ATP
      citrate lyase cDNA sequences reveals 96.3% amino acid identity throughout the
      entire sequence. Further sequence analysis identified the His765 catalytic
      phosphorylation site, the ATP-binding site, as well as the CoA binding site. The
      human ATP-citrate lyase cDNA clone was subcloned into a mammalian expression
      vector for expression in African green monkey kidney cells (COS) and Chinese
      hamster ovary cells (CHO) cells. Transfected COS cells expressed detectable
      levels of an enzymatically active recombinant ATP-citrate lyase enzyme. Stable,
      amplified expression of ATP-citrate lyase in CHO cells as achieved by using
      coamplification with dihydrofolate reductase. Resistant cells expressed high
      levels of enzymatically active ATP-citrate lyase (3 pg/cell/d). Site-specific
      mutagenesis of His765----Ala diminishes the catalytic activity of the expressed
      ATP-citrate lyase protein. Since catalysis of ATP-citrate lyase is postulated to
      involve the formation of phosphohistidine, these results are consistent with the
      pattern of earlier observations of the significance of the histidine residue in
      catalysis of the human ATP-citrate lyase.

PMID- 1371750
TI  - The nucleotide and partial amino acid sequences of rat fetuin. Identity with the
      natural tyrosine kinase inhibitor of the rat insulin receptor.
AB  - Fetuins are among the major plasma proteins, yet their biological role has
      remained elusive. Here we report the molecular cloning of rat fetuin and the
      sequence analysis of a full-length clone, RF619 of 1456 bp with an open reading
      frame of 1056 bp encoding 352 amino acid residues. The coding part of RF619 was
      identical with the cDNA sequence of the natural inhibitor of the insulin receptor
      tyrosine kinase from rat (pp63) except for four substitutions and a single base
      insertion causing divergence of the predicted protein sequences. Partial amino
      acid sequences of rat plasma fetuin were in agreement with the predictions based
      on the RF619 cDNA. Purified rat fetuin inhibited the insulin receptor tyrosine
      kinase in vitro. Therefore, we conclude that RF619 and pp63 cDNA encode the same
      protein, i.e. authentic rat fetuin which is a functional tyrosine kinase
      inhibitor.

PMID- 1371751
TI  - A membrane-bound metallo-endopeptidase from rat kidney. Characteristics of its
      hydrolysis of peptide hormones and neuropeptides.
AB  - A membrane-bound metallo-endopeptidase that hydrolyzes human parathyroid hormone
      (1-84) and reduced hen egg lysozyme between hydrophilic amino acid residues was
      isolated from rat kidney [Yamaguchi et al. (1991) Eur. J. Biochem. 200, 563-571].
      In this study, the hydrolyses of various peptide hormones and neuropeptides by
      the metallo-endopeptidase were examined using an automated gas-phase protein
      sequencer. The purified enzyme hydrolyzed the oxidized insulin B chain and
      substance P most rapidly, followed by big endothelin 1, neurotensin, angiotensin
      1, endothelin 1, rat alpha-atrial natriuretic peptide and bradykinin, in this
      order. The enzyme mainly cleaved these peptides at bonds involving a hydrophilic
      amino acid residue. However, it cleaved bonds between less hydrophilic amino acid
      pairs in several short peptides, e.g. at the His5-Leu6 bond in oxidized insulin B
      chain, the Ile28-Val29 bond in big endothelin-1 and the Ile5-His6 and Phe8-His9
      bonds in angiotensin 1. The enzyme cleavage sites of oxidized insulin B chain and
      angiotensin 1 were different from the reported sites cleaved by meprin and by
      endopeptidase 2, respectively. Kinetic determination of bradykinin hydrolysis by
      the purified enzyme yielded values of Km = 18.1 microM and kcat = 0.473 s-1,
      giving a ratio of kcat/Km = 2.62 x 10(4) s-1.M-1. The Km value was about 20-fold
      lower than that reported for meprin and endopeptidase 2. These results indicate
      that the membrane-bound metallo-endopeptidase from rat kidney is distinguished
      from meprin and endopeptidase 2 in its substrate specificity and is not
      parathyroid hormone specific, but has potential capacities to inactivate various
      biologically active peptide hormones and neuropeptides in vivo.

PMID- 1371752
TI  - Localization and accessibility of antigenic sites of the extracellular serine
      proteinase of Lactococcus lactis.
AB  - Lactococcus lactis strains produce an extracellular subtilisin-related serine
      proteinase in which immunologically different components can be distinguished.
      Monoclonal antibodies specific for the different proteinase components have been
      raised and their epitopes were identified. By Western-blot analysis it was found
      that all monoclonal antibodies recognize all denatured proteinase components. The
      distinction between the different components could be made under native
      conditions only, indicating that binding regions are masked in the native
      molecule. In a L. lactis proteinase which was inactivated by the substitution
      Asp30----Asn under native conditions, only one epitope could be detected. This
      demonstrates that autoproteolytic activity is required to make specific binding
      regions accessible for (monoclonal) antibodies.

PMID- 1371753
TI  - Molecular cloning and characterization of a constitutively expressed heat-shock
      cognate hsc71 gene from rainbow trout.
AB  - A rainbow trout major heat-shock-protein-like gene (hsp 70) and corresponding
      cDNA clones were isolated by hybridization to heterologous hsp70 probes. DNA
      sequencing revealed that this gene is structurally similar to a mammalian heat
      shock-cognate hsc70 gene and consists of eight introns. Northern blot and primer
      extension analyses showed that the corresponding mRNA is constitutively abundant
      in different trout tissues and salmonid cell lines. Fragments of the isolated
      gene containing the -900 - +30 and -217 - +58 sequence were linked to a bacterial
      chloramphenicol acetyltransferase reporter gene and transiently transfected into
      salmonid cells. The expression pattern of these constructs supports our
      conclusion that the isolated genomic and cDNA clones correspond to a trout heat
      shock-cognate hsc70 gene.

PMID- 1371754
TI  - Effects of brain-gut related peptides on cAMP levels in myenteric ganglia of
      guinea-pig small intestine.
AB  - This study was designed to test the hypothesis that stimulation of adenylate
      cyclase and elevation of cAMP is involved in the signal transduction process for
      substance P, calcitonin gene-related peptide, vasoactive intestinal peptide,
      cholecystokinin or gastrin releasing peptide in myenteric ganglia. Enzymatically
      dissociated ganglia from the myenteric plexus of the guinea-pig small intestine
      were used to study changes in levels of cAMP in response to application of the
      brain-gut peptides in the presence and absence of forskolin. Application of
      substance P and calcitonin gene-related peptide were found to increase
      intraganglionic cAMP in a dose-dependent fashion when a phosphodiesterase
      inhibitor was present. The ED50 values for substance P and calcitonin gene
      related peptide were 5 microM and 0.75 microM, respectively. The presence of
      forskolin in the incubation medium resulted in significant upward shifts of the
      dose-response curves for both peptides. Neither vasoactive intestinal peptide,
      cholecystokinin nor gastrin releasing peptide stimulated increases in
      intraganglionic cAMP under the same experimental conditions used for substance P
      and calcitonin gene-related peptide.

PMID- 1371755
TI  - Synthesis and secretion of alpha 2-macroglobulin by human glioma established cell
      lines.
AB  - Human alpha 2-macroglobulin (alpha 2M) is a high molecular weight plasma
      proteinase inhibitor exhibiting a broad specificity; in fact it is capable of
      binding endopeptidases from all known classes of proteases (Barret 1981). Two
      human glioma cell lines, namely an astrocytoma and a glioblastoma, were found to
      synthesize and secrete in the culture medium a protein which resembles the serum
      alpha 2M for immunological, biochemical and biological features. Using polyclonal
      antibodies to serum alpha 2M, an alpha 2M-like factor could be detected in the
      cytoplasm and in the culture medium of the tumor cells. Furthermore this factor
      accumulated in cytoplasmic granules if cells were incubated with monensin and its
      production was dramatically reduced following a treatment with cycloheximide.
      This protein behaved like the serum alpha 2M in immunoblotting analysis and
      exhibited the same antiproteolytic activity. Its role in human brain is unknown
      at present. Since interactions of proteinases and proteinase-inhibitors appear to
      influence the host-tumor immune response and to play a crucial role during the
      migration of metastasizing tumor cells, alpha 2M expression observed in these
      glioma cells could be involved in tumor cell proliferation and invasion.

PMID- 1371756
TI  - Ultrastructural changes in the hippocampal CA1 region following transient
      cerebral ischemia: evidence against programmed cell death.
AB  - The ultrastructural changes in the pyramidal neurons of the CA1 region of the
      hippocampus were studied 6 h, 24 h, 48 h, and 72 h following a transient 10 min
      period of cerebral ischemia induced by common carotid occlusion combined with
      hypotension. The pyramidal neurons showed delayed neuronal death (DND), i.e. at
      24 h and 48 h postischemia few structural alterations were noted in the light
      microscope, while at 72 h extensive neuronal degeneration was apparent. The most
      prominent early ultrastructural changes were polysome disaggregation, and the
      appearance of electron-dense fluffy dark material associated with tubular
      saccules. Mitochondria and nuclear elements appeared intact until frank neuronal
      degeneration. The dark material accumulated with extended periods of
      recirculation in soma and in the main trunks of proximal dendrites, often beneath
      the plasma membrane, less frequently in the distal dendrites and seldom in
      spines. Protein synthesis inhibitors (anisomycin, cycloheximide) and an RNA
      synthesis inhibitor (actinomycin D), administered by intrahippocampal injections
      or subcutaneously, did not mitigate neuronal damage. Therefore, DND is probably
      not apoptosis or a form of programmed cell death. We propose that the dark
      material accumulating in the postischemic period represents protein complexes,
      possibly aggregates of proteins or internalized plasma membrane fragments, which
      may disrupt vital cellular structure and functions, leading to cell death.

PMID- 1371757
TI  - Angiotensin converting enzyme inhibition prevents development of muscle and nerve
      dysfunction and stimulates angiogenesis in streptozotocin-diabetic rats.
AB  - The effects of the angiotensin converting enzyme inhibitor lisinopril on slow and
      fast twitch muscle contractile properties, nerve conduction and hypoxic
      resistance, and muscle and nerve capillary density were examined in
      streptozotocin-diabetic rats. Prolongation of soleus contraction and relaxation
      were partially prevented by treatment (p less than 0.01). A 22% deficit in fast
      twitch extensor digitorum longus tetanic tension production was also ameliorated
      (p less than 0.01). Sciatic motor and sensory conduction velocity, 25% and 12%
      reduced by diabetes respectively, were 75% normalized by lisinopril (p less than
      0.01). There was a 47% increase in resistance to hypoxic conduction block with
      diabetes (p less than 0.01). Lisinopril treatment resulted in normal hypoxic
      resistance. Capillarization of nerve and muscle was little affected by diabetes;
      however, there was a 17% increase in capillary density in sciatic nerve, and a
      40% increase in extensor digitorum longus muscle with lisinopril (p less than
      0.01). For soleus, a smaller treatment-induced increase in capillary density led
      to an elevated capillary/muscle fibre ratio (p less than 0.01). These results
      suggest that lisinopril promoted angiogenesis. It was concluded that the
      beneficial effect of preventive lisinopril treatment is likely to depend upon a
      reduction of peripheral vascular resistance and improvement of tissue blood flow,
      which implicates relative hypoxia as an important factor in the development of
      myopathy and neuropathy in experimental diabetes.

PMID- 1371758
TI  - Molecular genetic analysis of the mldr mouse: a spontaneous revertant at the mld
      locus containing a recombinant myelin basic protein gene.
AB  - The mld mutation is a complex genetic lesion affecting the myelin basic protein
      (MBP) locus in the mouse. The mutation consists of a variety of DNA
      rearrangements including: tandem duplication of the MBP structural gene, partial
      inversion of the 3' end of the upstream gene copy, duplication of a region
      flanking the rearrangement junction in the upstream copy and insertion between
      the two gene copies of a segment of extraneous DNA not associated with the wild
      type MBP locus. The net result of the mutation is a dysfunctional MBP locus.
      Homozygous mld/mld mice produce very little MBP and consequently very little
      myelin. They exhibit a clinical phenotype characteristic of hypomyelination
      (shaking, convulsions). We have discovered a revertant mld mouse which does not
      exhibit clinical symptoms of hypomyelination. Genetic analysis indicates that the
      reversion is allelic to mld. We have designated the revertant locus mldr.
      Restriction analysis of mldr genomic DNA indicates that there is a single intact
      MBP gene. Analysis of various junction regions using the polymerase chain
      reaction indicates that the single MBP gene in mldr is derived by recombination
      from the 5' end of the upstream gene and the 3' end of the downstream gene.
      Studies on MBP expression in mldr mice indicate that the developmental
      regulation, level of expression and pattern of post-transcriptional processing of
      MBP gene products in mldr are similar to wild type. These results indicate that
      the recombinant MBP gene in mldr is fully functional. From this we infer that the
      MBP-deficient phenotype of the original mld mutant is attributable to the complex
      rearrangements in the upstream gene copy which render the locus
      dysfunctional.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371759
TI  - Synthetic human tRNA(UUULys3) and natural bovine tRNA(UUULys3) interact with HIV
      1 reverse transcriptase and serve as specific primers for retroviral cDNA
      synthesis.
AB  - Full-length and 5'-truncated variants of human (h) tRNA(UUULys3) were synthesized
      by in vitro transcription using SP6 RNA polymerase. Bovine(b) tRNA(SUULys3) was
      purified from calf liver. Both full-length tRNA species were shown to be
      biologically active in an aminoacylation assay. Gel retardation assays revealed
      that both full-length tRNA species, as well as a 5'-truncated h-tRNA(UUULys3)
      molecule containing 24 nucleotides (nt) at the 3' end (Lys24), interact with
      human immunodeficiency virus (HIV)-1 reverse transcriptase (RT). Competition
      studies with these three tRNA species demonstrate that the 3' end of h
      tRNA(UUULys3) contributes to the interaction with HIV-1 RT. Escherichia coli
      tRNA(UUULys) and tRNA(UUCGlu2) were also able to interact with the enzyme,
      whereas unrelated RNA molecules such as E. coli 5S rRNA did not bind to RT. Both
      b-tRNA(SUULys3) and h-tRNA(UUULys3) molecules, as well as the 5'-truncated
      variants, could be demonstrated to prime cDNA synthesis specifically using a HIV
      1 RNA template, prepared by in vitro transcription, indicating that other viral
      or cellular proteins are not essential for this process. E. coli tRNA(UUULys) and
      tRNA(UUCGlu2), although able to interact with HIV-1 RT, failed to prime
      retroviral transcription. Products of cDNA synthesis were characterized by
      polymerase chain reaction, demonstrating that at least 18 nt at the 3' ends of h
      tRNA(UUULys3) and b-tRNA(SUULys3) are still present in the cDNA product, whereas
      the 5' ends of both primer molecules were removed by the RNase H activity of HIV
      1 RT.

PMID- 1371760
TI  - Studies of gut mucosal protein synthesis in a non-steroidal anti-inflammatory
      drug (NSAID) model of inflammatory bowel disease.
AB  - The extent to which defects in protein synthesis occurred in an experimental
      indomethacin induced rat model of nonsteroidal enteropathy has been examined.
      Male rats (nine) were fed indomethacin (8 mg/kg/day) for three days mixed with a
      powdered form of chow. The control group of rats (nine) were fed the same diet
      for three days without indomethacin. After the feeding period, both groups were
      fed a normal solid diet for four days. At the end of this period, the fractional
      rates of intestinal protein synthesis was determined by the 'flooding dose'
      technique. The mucosal protein, RNA and DNA contents in the proximal ileum of
      animals with enteropathy were not significantly different from controls (p
      greater than 0.05). Experimental enteropathy induced selective increases in the
      fractional rates of protein synthesis (26% increase, p less than 0.03) and RNA
      activities (23% increase, p less than 0.04). There were no significant changes in
      any of these variables in the duodenum (p greater than 0.05 in all instances).
      These changes may partly reflect the activity of those processes responsible for
      the pathogenic changes in NSAID enteropathy.

PMID- 1371761
TI  - Aggressive extracorporeal shock wave lithotripsy of gall bladder stones within
      wider treatment criteria: fragmentation rate and early results.
AB  - Two hundred and twenty patients with a total of 412 gall bladder stones of
      between 8 and 38 mm in size were treated with extracorporeal shock wave
      lithotripsy, using the overhead module Lithostrar Plus. Fifty six per cent of
      stones were solitary (mean (SD) diameter 23 (5) mm) and 9.5% of the patients had
      more than three stones. Stones were successfully disintegrated in 218 patients
      (fragmentation size less than 5 mm in 80%, less than 10 mm in 19%). Some 65% of
      patients required one treatment and the rest two or three. A mean (SD) of 4100
      (1800) shock waves with a pressure of 700 bar were applied. Twenty four to 48
      hours after lithotripsy a transient but significant increase in serum
      transaminase activities (31%) and in bilirubin (29%), urinary amylase (27%), and
      blood leukocyte (62%) values was observed. In 29% of patients there was a
      transient microhaematuria, in 2% transient macrohaematuria, and in 25% painless
      petechiae of the skin. Ultrasound showed temporary gall bladder wall oedema in
      13%, temporary distension of the gall bladder in 11%, and transient common bile
      duct distension in 8% after treatment. After discharge from hospital, 31% of
      patients complained of recurrent colic that responded to simple analgesics. Four
      to eight weeks after therapy, four patients developed biliary pancreatitis and 11
      biliary obstruction that was managed by endoscopy. To date, 105 patients have
      been followed for over 12 months. Sixty one of these had a solitary stone, 17 had
      two, and 27 had three or more stones. A total of 59 patients, including 44 with a
      primary solitary stone, eight with two stones, and seven with three or more
      stones are completely stone free.

PMID- 1371762
TI  - High conductance anion channel in Schwann cell vesicles from rat spinal roots.
AB  - Potassium uptake, possibly together with chloride, is one of the presumed
      functions of Schwann cells in the peripheral nervous system. However, the
      presence of chloride channels has not been demonstrated in adult Schwann cells.
      We present here a new method which allows single channel recordings to be made
      from Schwann cells in situ without enzymatic treatment. Isolated rat spinal roots
      were split mechanically into several bundles. Within about 30 min after this
      procedure small bleb-like vesicles (approximately 20-30 microns in diameter) with
      a clean surface appeared at the edges of the fibre bundles. Immunofluorescence
      microscopy with a surface marker for Schwann cell membranes (monoclonal antibody
      O4) revealed that the vesicles originate from Schwann cells. In standard patch
      clamp recordings with symmetrical bath and pipette solutions (excised inside-out
      configuration) an anion channel with the following characteristics was mainly
      observed: 1) single channel slope conductance of 337 +/- 5 pS in 125 mM KCl and
      209 +/- 6 pS in 125 mM K+ methylsulphate; 2) ion permeability ratio:
      PCl/PK/Pgluconate = 1/0.12/0.06; 3) linear current-voltage relationship (range +/
      60 mV); and 4) voltage- and time-dependent inactivation (the channel was most
      active at potentials +/- 20 mV). Pharmacologically, the channel was completely
      blocked with zinc (1 mM) and barium (10 mM). A similar anion channel, showing
      characteristics 1-4), has been described in cultured Schwann cells of newborn
      rats (Gray et al., 1984). We now demonstrate that this channel is also present in
      adult Schwann cells in situ.

PMID- 1371763
TI  - Binding of monoclonal antibody specific for domain Ia/II of Pseudomonas
      aeruginosa exotoxin A at pH 4 strongly neutralizes exotoxin A-induced
      cytotoxicity in cell culture and in vivo.
AB  - Mouse monoclonal antibodies (MAbs) against Pseudomonas aeruginosa exotoxin A (Ex
      A) were established, and 4 of 20 MAbs were extensively studied for analysis of
      the structure-function relationship of Ex-A. IN vivo experiments demonstrated
      that MAb Ex-3C7 protected mice either injected with Ex-A or infected with Ex-A
      producing P. aeruginosa from death caused by Ex-A at the highest rate, followed
      by MAbs Ex-4F2 and Ex-8H5, in that order. MAb Ex-2A10 failed to rescue the mice.
      MAb Ex-3C7 (immunoglobulin G1 [IgG1]) inhibited incorporation of Ex-A into target
      cells and strongly neutralized cytotoxicity in cell culture but did not inhibit
      an enzymatic activity of Ex-A, ADP-ribosyltransferase, at all. The MAb also bound
      Ex-A, even at a low pH of 4, and recognized amino acid residues 241 to 297
      (domain Ia/II), suggesting that MAb Ex-3C7 can interfere with the conformational
      change and/or processing of Ex-A by keeping a complex of Ex-A and antibody stable
      at low pH in the phagolysosome. MAb Ex-4F2 (IgG1), which recognizes residues 550
      to 590 (domain III), strongly inhibited Ex-A incorporation and neutralized
      cytotoxicity in cell culture but only weakly inhibited ADP-ribosyltransferase.
      MAb Ex-8H5 (IgG1), which recognizes residues 591 to 613 (domain III), also
      inhibited cytotoxicity in cell culture, but weakly. In contrast to the above
      three MAbs, MAb Ex-2A10 (IgG2b) greatly inhibited ADP-ribosyltransferase but
      showed no inhibition of Ex-A incorporation and no neutralizing activity against
      cell toxicity. A line of evidence indicates that (i) domain Ia/II plays an
      important role in the pathogenesis of Ex-A and (ii) MAbs that inhibit an
      intracellular postbinding process, such as conformational change, processing, and
      translocation of Ex-A in target cells, can display potent inhibitory activity
      against cytotoxicity in vivo, as well as in cell culture, and would be a good
      candidate for therapy of pseudomonal infections.

PMID- 1371764
TI  - Longitudinal study of Plasmodium falciparum polymorphic antigens in a malaria
      endemic population.
AB  - Plasmodium falciparum merozoite surface antigens MSP1 and MSP2 and an exported
      antigen, Exp-1, exhibit allelic polymorphism in natural populations. To explain
      this, one hypothesis is that antigen polymorphisms are maintained by frequency
      dependent immune selection. An expectation of the hypothesis is that rare
      variants have an advantage over common variants because of a lower level of
      acquired immunity against them and thus increase in frequency until an
      equilibrium is attained. To test this hypothesis, the frequencies of polymorphic
      epitopes of MSP1, MSP2, and Exp-1 were determined among isolates from malaria
      patients in an urban area of The Gambia, during different periods of one
      transmission season (1988) and in different years (1982, 1983, 1988, and 1989).
      The frequencies remained very stable throughout the period of study, alternative
      epitope variants remaining either rare or common, without shifts in relative
      frequencies. These results are discussed with reference to the immune-selection
      hypothesis, with the conclusion that frequencies of the major dimorphic
      serological classes of MSP1 are probably not maintained by immune selection.

PMID- 1371765
TI  - Cloning and expression of the gene for the Avi-3 antigen of Mycobacterium avium
      and mapping of its epitopes.
AB  - The Avi-3 antigen, which is found only in Mycobacterium avium culture sonic
      extracts, is species specific and results in strong skin test activity in guinea
      pigs sensitized with heat-killed M. avium. Its gene was cloned by using a
      previously developed single-probe method and was sequenced. The gene encoded a
      194-amino-acid polypeptide with a molecular weight of 21,500. A recombinant Avi-3
      antigen expressed in Escherichia coli reacted with monoclonal and polyclonal
      antibodies raised against the native Avi-3 antigen. To identify epitopes on this
      protein for immunodiagnostic purposes, various parts of the Avi-3 antigen were
      expressed as beta-galactosidase fusion proteins, using pUR and pURS expression
      vectors. The clones screened by both antibody reactivity and T-cell proliferative
      activity defined fragments with coexisting B- and T-cell epitopes. A B-cell
      epitope (Asn-176 to Ala-186) and two T-cell epitopes (Glu-75 to Ile-86 and Arg
      155 to Leu-164) were thus defined. The synthetic polymerized peptides of the T
      cell epitopes were proven to elicit a delayed cutaneous hypersensitivity reaction
      in guinea pigs. This mapping method would be useful in the development of a
      subunit vaccine consisting of an immunodominant B-cell epitope linked to a T-cell
      epitope in the vicinity.

PMID- 1371766
TI  - Colonization factor antigen CFA/IV (PCF8775) of human enterotoxigenic Escherichia
      coli: nucleotide sequence of the CS5 determinant.
AB  - Human enterotoxigenic Escherichia coli isolates expressing the colonization
      factor antigen CFA/IV (previously designated PCF8775) produce plasmid-encoded CS5
      fimbriae. The nucleotide sequence of the region encoding the major CS5 fimbrial
      subunit was determined. The subunit is synthesized as a precursor of 203 amino
      acids (20.85 kDa) with a mature protein of 181 amino acids corresponding to a
      size of 18.6 kDa. The CS5 subunit shows homology to the corresponding component
      of porcine enterotoxigenic E. coli F41, particularly within the signal sequence
      and at the carboxy terminus.

PMID- 1371767
TI  - Role of mycoplasma infection in the cytopathic effect induced by human
      immunodeficiency virus type 1 in infected cell lines.
AB  - In addition to previously reported tetracycline analogs, other antibiotics known
      for antimycoplasmal activities inhibited the cytopathic effect in CEM cl13 cells
      infected with human immunodeficiency virus type 1 (HIV-1) or HIV-2 but were
      unable to block virus replication. A contaminating mycoplasma was isolated from
      our CEM cl13 cells and identified as a strain of Mycoplasma fermentans. Following
      infection of lymphoblastoid (CEM) or promonocytic (U937 and THP1) cell lines with
      HIV-1, cytopathic effect was observed only in association with mycoplasmal
      contamination. Moreover, HIV-1 infection of U937 cells after experimental
      inoculation with a human isolate of M. fermentans led to pronounced cell killing.
      We have verified that this effect is not merely an artifact caused by arginine
      and/or glucose depletion in the cell culture medium. These results confirm that
      mollicutes, in particular M. fermentans, are able to act synergistically with HIV
      1 to kill infected cells in some in vitro systems.

PMID- 1371768
TI  - Conserved outer membrane protein of Neisseria meningitidis involved in capsule
      expression.
AB  - In Neisseria meningitidis, translocation of capsular polysaccharides to the cell
      surface is mediated by a transport system that fits the characteristics of ABC
      (ATP-binding cassette) transporters. One protein of this transport system, termed
      CtrA, is located in the outer membrane. By use of a CtrA-specific monoclonal
      antibody, we could demonstrate that CtrA occurs exclusively in N. meningitidis
      and not in other pathogenic or nonpathogenic Neisseria species. Nucleotide
      sequence comparison of the ctrA gene from different meningococcal serogroups
      indicated that CtrA is strongly conserved in all meningococcal serogroups,
      independent of the chemical composition of the capsular polysaccharide. Secondary
      structure analysis revealed that CtrA is anchored in the outer membrane by eight
      membrane-spanning amphipathic beta strands, a structure of proteins that function
      as porins.

PMID- 1371769
TI  - Characterization of an antigenically conserved heat-modifiable major outer
      membrane protein of Branhamella catarrhalis.
AB  - Branhamella catarrhalis is a common cause of otitis media in children and of
      respiratory infections in adults with chronic bronchitis. Little is known about
      the antigenic structure of the outer membrane proteins (OMPs). In this study, two
      murine monoclonal antibodies, 7D6 and 5E8, were developed and used to
      characterize the major heat-modifiable OMP (OMP C/D) of B. catarrhalis.
      Immunoblot assays indicated that OMP C/D is heat modifiable, having a molecular
      mass of 55 kDa at room temperature and a mass of 60 kDa when heated under
      reducing conditions. Expression of the epitopes is independent of growth phase
      and growth media. Both epitopes are present in 51 of 51 strains of B. catarrhalis
      tested and are highly specific for Branhamella strains, being absent from a
      variety of other gram-negative species. Antibody 5E8 recognizes an epitope which
      is expressed on the surface of the intact bacterium. We conclude that OMP C/D is
      a major, heat-modifiable OMP antigen that expresses at least one stable,
      conserved epitope on the surface of B. catarrhalis. Future studies should focus
      on the role of OMP C/D in pathogenesis and on its potential role as a vaccine
      antigen.

PMID- 1371770
TI  - Identification and characterization of lipopolysaccharide-binding proteins on
      human peripheral blood cell populations.
AB  - Previous research in this laboratory, using photoactivatable radioiodinated
      lipopolysaccharide derivatized with sulfosuccinimidyl-2-(p-azidosalicylamide)
      1,3'-dithiopropionate (125I-ASD-LPS), has resulted in the identification of a
      specific LPS receptor with a molecular mass of approximately 73 kDa on murine
      lymphocytes and splenic macrophages. The experiments presented in this report
      investigated whether a similar LPS-binding protein was also expressed on human
      peripheral blood populations, including monocytes, lymphocytes, neutrophils,
      platelets, and erythrocytes. Each cell population was incubated with 125I-ASD
      LPS, UV irradiated, washed, reduced, and solubilized, and the cell lysates were
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by
      autoradiography. On all of the cell populations, except erythrocytes, a similar
      73-kDa LPS-binding protein was present. In addition, each population also
      expressed lower-molecular-weight secondary LPS-binding proteins, some of which
      were conserved among the populations. Binding of the photoactivatable LPS probe
      was found to be both time and temperature dependent. These data support the
      concept that the 73-kDa LPS-binding protein is conserved on multiple cell types
      from a variety of species.

PMID- 1371771
TI  - Plasmodium falciparum-infected erythrocytes do not adhere well to C32 melanoma
      cells or CD36 unless rosettes with uninfected erythrocytes are first disrupted.
AB  - Plasmodium falciparum malaria parasites modify the human erythrocytes in which
      they grow so that some parasitized erythrocytes (PE) can cytoadhere (C+) to host
      vascular endothelial cells or adhere in rosettes (R+) to uninfected erythrocytes.
      These C+ and R+ adherence properties of PE appear to mediate much of the
      pathogenesis of severe malaria infections, in part by blocking blood flow in
      microvessels. From one parasite strain, PE were selected in vitro for C+ R+ or C+
      R- adherence properties and examined in model adherence assays. The C+ R+ PE
      cytoadhered poorly to C32 melanoma cells or to immobilized CD36 in a settled-cell
      assay when uninfected human erythrocytes were present and formed rosettes with
      PE. C+ R- PE adhered well in the same assays. However, C+ R+ PE adhered very
      well, even better than C+ R- PE, when the rosettes were disrupted and the C+ R+
      PE were purified. Adding back rabbit erythrocytes, which do not form rosettes
      with C+ R+ PE, had simply a dilutional effect. The ability of rosettes to
      interfere with the detection of adherence must be dealt with in all future assays
      of malarial PE adherence. Individual PE were observed attached simultaneously to
      C32 cells and to a few erythrocytes, suggesting that C+ and R+ adherence
      properties are coexpressed on the same PE. Coexpression of these adherence
      properties on the same PE may have pathological importance in vivo, where passage
      of rosettes through capillaries may shear uninfected erythrocytes from rosetted
      PE and allow direct PE attachment to postcapillary venule walls before rosettes
      reform.

PMID- 1371772
TI  - Efficacy of copper and silver ions with iodine in the inactivation of Pseudomonas
      cepacia.
AB  - Alternatives to chlorination of water have been sought for reasons which include
      trihalomethane formation, possible bacterial regrowth, the high concentrations of
      chlorine required in certain circumstances, and the taste, odour and bodily
      irritation in chlorine-treated water. Electrolytically generated Cu and Ag ions
      at low levels, in addition to very low chlorine concentrations, have been
      suggested as an alternative to routine chlorination. We have examined the
      combination of Cu and Ag ions with low levels of iodine. Pseudomonas cepacia was
      grown either in rich medium or under nutrient restriction prior to disinfection.
      Survival of the organism and its ability to regrow after treatment as well as the
      effects of varying buffers, metal ion and iodine concentrations were determined.
      Low concentrations of metal ions (100 ppb Cu and 11 ppb Ag) and iodine (200 ppb)
      were more effective than either metal ions or iodine alone against Ps. cepacia
      grown on rich agar or in low nutrient buffer. After iodination, buffer-grown
      suspensions recovered to their original cell concentrations within 7 d. When Cu
      and Ag ions were used with or without iodine, regrowth was prevented. The results
      show that low concentrations of Cu and Ag in combination with iodine permit
      effective disinfection of bacteria after cultivation on either rich media or
      under nutrient restriction. These results, along with published data, suggest
      that the combination of these metals with halogenation may have applications in
      the disinfection of both recreational and potable water.

PMID- 1371774
TI  - Preserved endothelium-dependent vasodilation at the vasospastic site in patients
      with variant angina.
AB  - Endothelial dysfunction has been implicated as a cause of coronary vasospasm in
      patients with variant angina. This study aimed to determine if endothelium
      dependent vasodilation evoked with substance P (SP) was altered at the spastic
      site where vasospasm was induced by acetylcholine (ACH) in patients with variant
      angina. It has been shown that SP evokes endothelium-dependent vasodilation with
      no direct effect on vascular smooth muscle in excised human coronary arteries. SP
      and ACH were infused into the coronary arteries in nine patients with variant
      angina in whom coronary arteriograms showed normal or mild atherosclerotic
      lesions. The vasomotor responses of coronary arteries were assessed by
      quantitative arteriography. ACH at a high dose (100 micrograms/min) provoked
      coronary vasospasm associated with anginal attack in all patients. In contrast,
      SP at graded doses (13.5, 40, and 135 ng/min) caused the dose-dependent and
      comparable increases in the coronary diameter at the spastic and control sites.
      ACH at a low dose (10 micrograms/min) also caused comparable vasodilation at the
      spastic and control sites in patients with normal coronary arteries. Coronary
      vasodilating responses to SP were comparable in patients with variant angina and
      those with atypical chest pain. The results indicate that endothelium-dependent
      vasodilation evoked with SP and ACH at the low dose was present at the
      vasospastic site in patients with variant angina. These findings suggest that the
      ACH-induced coronary vasospasm in patients with variant angina results from
      hyperreactivity of vascular smooth muscle to ACH but not from endothelial
      dysfunction.

PMID- 1371773
TI  - Tenascin promotes cerebellar granule cell migration and neurite outgrowth by
      different domains in the fibronectin type III repeats.
AB  - The extracellular matrix molecule tenascin has been implicated in neuron-glia
      recognition in the developing central and peripheral nervous system and in
      regeneration. In this study, its role in Bergmann glial process-mediated neuronal
      migration was assayed in vitro using tissue explants of the early postnatal mouse
      cerebellar cortex. Of the five mAbs reacting with nonoverlapping epitopes on
      tenascin, mAbs J1/tn1, J1/tn4, and J1/tn5, but not mAbs J1/tn2 and J1/tn3
      inhibited granule cell migration. Localization of the immunoreactive domains by
      EM of rotary shadowed tenascin molecules revealed that the mAbs J1/tn4 and
      J1/tn5, like the previously described J1/tn1 antibody, bound between the third
      and fifth fibronectin type III homologous repeats and mAb J1/tn3 bound between
      the third and fifth EGF-like repeats. mAb J1/tn2 had previously been found to
      react between fibronectin type III homologous repeats 10 and 11 of the mouse
      molecule (Lochter, A., L. Vaughan, A. Kaplony, A. Prochiantz, M. Schachner, and
      A. Faissner. 1991. J. Cell Biol. 113:1159-1171). When postnatal granule cell
      neurons were cultured on tenascin adsorbed to polyornithine, both the percentage
      of neurite-bearing cells and the length of outgrowing neurites were increased
      when compared to neurons growing on polyornithine alone. This neurite outgrowth
      promoting effect of tenascin was abolished only by mAb J1/tn2 or tenascin added
      to the culture medium in soluble form. The other antibodies did not modify the
      stimulatory or inhibitory effects of the molecule. These observations indicate
      that tenascin influences neurite outgrowth and migration of cerebellar granule
      cells by different domains in the fibronectin type III homologous repeats.

PMID- 1371775
TI  - Monocyte chemotactic and activating factor is a potent histamine-releasing factor
      for basophils.
AB  - Monocyte chemotactic and activating factor (MCAF) is a recently cloned cytokine
      that causes chemotaxis of basophils. In our pursuit of cytokines affecting
      basophil function, we studied the effect of MCAF on histamine secretion from
      basophils. Leukocytes from 20 donors, 10 allergic and 10 normal subjects, were
      studied. MCAF caused dose-dependent release of histamine at concentrations of 10(
      8) and 10(-7) M, and the mean release was 31.25 +/- 2.9% at the highest
      concentration. In the same experiments the mean histamine release by anti-IgE and
      histamine releasing factor (HRF) was 27.05 +/- 4% and 32.70 +/- 2.7%,
      respectively. All 20 subjects responded to MCAF with significant histamine
      release. Allergic subjects released significantly more histamine than normals in
      response to anti-IgE (P less than 0.01) but not to MCAF (P = 0.2) and HRF (P =
      0.1). The histamine release was significantly correlated between MCAF and HRF (P
      less than 0.01), but not between MCAF and anti-IgE (P greater than 0.05). The
      histamine release by MCAF was complete within the first 3 min. MCAF-induced
      degranulation was a calcium-dependent process. Leukocytes depleted of monocytes
      responded equally well to MCAF. Using an anti-MCAF affinity column we determined
      that greater than 50% of HRF activity of crude PBMC supernatant could be
      attributed to MCAF. Thus, we established that MCAF is a potent secretagogue for
      basophils.

PMID- 1371776
TI  - Oestrogen receptor analysis: correlation between enzyme immunoassay and
      immunohistochemical methods.
AB  - AIMS: To compare oestrogen receptor measurements on fresh tissue done by an
      enzyme immunoassay (ER-EIA, Abbott) and an immunohistochemical technique (ER-ICA,
      Abbott) using formalin fixed, paraffin was embedded material. METHODS: The ER-EIA
      is based on a sandwich immunoassay using fresh frozen tissue, and the absorbance
      values were read by a Quantum Analyzer. Sections were cut from the corresponding
      paraffin wax blocks, and after pretreatment with pronase and DNase, the slides
      were incubated with monoclonal oestrogen antibody. The immunoperoxidase staining
      was scored semiquantitatively, incorporating both the intensity and percentage of
      positive staining (HSCORE). RESULTS: HSCORE rating of the ER-ICA slides gave a
      significant correlation with the quantitative ER-EIA values (r = 0.76; p less
      than 0.001). The overall sensitivity and specificity of the immunohistochemical
      method was 88% and 93%, respectively. CONCLUSIONS: ER-ICA on routinely processed
      material can be a valuable alternative when biochemical analysis of oestrogen
      receptor content is not available. Furthermore, immunohistochemical staining
      identifies oestrogen receptor positivity at a cellular level, which ensures that
      the analysed material is representative. This technique could therefore be
      particularly valuable in small tumours and in situ lesions.

PMID- 1371777
TI  - Heterogeneity of vascular endothelial cells with relevance to diagnosis of
      vascular tumours.
AB  - AIMS: To determine the distribution of factor VIII related antigen, CD31, CD34
      and CD36 in normal and malignant human vascular tissues using a panel of well
      characterised monoclonal antibodies. METHODS: Frozen and fixed material from a
      wide range of normal tissues and routinely processed material from 43 benign and
      malignant vascular tumours were examined. Single immunocytochemical labelling was
      performed using the APAAP technique. Double staining involved the sequential use
      of APAAP with the peroxidase method. RESULTS: Human vascular endothelium was
      antigenically heterogeneous. One of the most restricted markers was factor VIII
      related antigen, despite its having been widely used in diagnostic pathology as a
      marker of vascular endothelium and of the tumours which arise from it. Three
      antibodies against factor VIII related antigen, CD31 (JC70) and CD34 (QBend 10)
      were identified as immunostaining routinely processed, formalin fixed, paraffin
      wax sections. Each antibody gave different staining when tested on a range of
      vascular tumours, both benign and malignant. CONCLUSIONS: A small panel of three
      reagents (factor VIII related antigen, CD31 (JC70) and CD34 (QBend 10)) should be
      used by diagnostic pathologists who want to show the presence of cells of
      endothelial origin in routine material.

PMID- 1371778
TI  - Gastric histamine concentration and IgE in Helicobacter pylori infection.

PMID- 1371779
TI  - Reciprocal connections between the medial preoptic area and the midbrain
      periaqueductal gray in rat: a WGA-HRP and PHA-L study.
AB  - The midbrain periaqueductal gray (PAG) participates in diverse functions such as
      analgesia, autonomic regulation, sexual behavior, and defense/escape responses.
      Anatomical studies of the circuits involved in such functions have largely
      focused on the connections of PAG with the medulla. Projections to PAG from
      forebrain structures are extensive, but their organization has received little
      attention. Previous anatomic studies indicate that the medial preoptic area
      (MPO), involved in a variety of physiological and behavioral functions, is a
      major source of afferent input to the periaqueductal gray. Here, we have examined
      the topography of reciprocal connections between these two structures in the rat
      by using wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) and
      Phaseolus vulgaris leucoagglutinin (PHA-L). Multiple WGA-HRP injections at
      several rostrocaudal levels of PAG retrogradely labeled large numbers of neurons
      in the medial preoptic area; labeled cells were primarily located in the medial
      preoptic nucleus, the median preoptic nucleus, and the region lateral to the
      medial preoptic nucleus. The distribution of labeled cells shifted medially to
      laterally along the rostral to caudal axis of the medial preoptic area.
      Rostrally, there was selective retrograde labeling in the central and lateral
      divisions of medial preoptic nucleus, whereas caudally, labeled cells were
      primarily located only in the lateral subdivision of medial preoptic nucleus.
      Tracer injections in PAG also produced strong anterograde labeling in MPO. WGA
      HRP and PHA-L injections in the medial preoptic area resulted in dense
      anterograde labeling along the entire rostrocaudal axis of PAG. The terminal
      labeling in PAG from the medial preoptic area was not uniformly distributed
      throughout PAG, however. Instead, this projection formed one or two
      rostrocaudally oriented longitudinal columns that terminated in different
      subregions of PAG along the entire rostrocaudal axis of this structure.
      Rostrally, inputs from the medial preoptic area project heavily to dorsomedial
      PAG, and at mid-PAG levels, the projection becomes distinctly bipartite with two
      discrete longitudinal terminal columns in dorsomedial and lateral PAG; caudally,
      the heaviest labeling is in ventrolateral PAG. The projection also exhibited a
      central to peripheral (radial) gradient; labelled fibers and terminals were
      heaviest near the aqueduct and much lower in the peripheral parts of PAG. WGA-HRP
      injections in MPO also produced retrograde labeling of neurons at all
      rostrocaudal levels of PAG; more neurons were labeled in the rostral than the
      caudal half of PAG. The majority of labeled cells were located in dorsomedial and
      ventral/ventrolateral parts of PAG; only a few neurons in the dorsal raphe region
      appear to project to MPO.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1371780
TI  - Organization of medullary adrenergic and noradrenergic projections to the
      periaqueductal gray matter in the rat.
AB  - The periaqueductal or midbrain central gray matter (CG) in the rat contains a
      dense network of adrenergic and noradrenergic fibers. We examined the origin of
      this innervation by using retrograde and anterograde axonal tracers combined with
      immunohistochemistry for the catecholamine biosynthetic enzymes tyrosine
      hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N
      methyltransferase (PNMT). Following injections of the fluorescent tracers Fast
      Blue or Fluorogold into the CG, double-labeled neurons in the medulla were
      identified mainly in the noradrenergic A1 group in the caudal ventrolateral
      medulla (VLM) and A2 group in the medial part of the nucleus of the solitary
      tract (NTS); and in the adrenergic C1 group in the rostral ventrolateral medulla
      and C3 group in the rostral dorsomedial medulla. Injections of Phaseolus vulgaris
      leucoagglutinin (PHA-L) into these cell groups resulted in a distinct pattern of
      axonal labeling in various subdivisions of the CG. Anterogradely labeled fibers
      originating in the medial NTS were predominantly found in the lateral portion of
      the dorsal raphe nucleus and in the adjacent part of the lateroventral CG (CGlv).
      Following PHA-L injections into the C3 region the anterogradely labeled fibers
      were diffusely distributed in the CGlv and the dorsal raphe nucleus at caudal
      levels, but rostrally tended to be located laterally in the CGlv. In contrast,
      ascending fibers from the caudal and rostral VLM terminated in the rostral dorsal
      part of the CGlv and in the dorsal nucleus of the CG, whereas ventral parts of
      the CG, including the dorsal raphe nucleus, contained few afferent fibers. Double
      label studies with antisera against DBH and PNMT confirmed that noradrenergic
      neurons in the A1 and A2 groups and adrenergic neurons in the C1 and C3 groups
      contributed to these innervation patterns in the CGlv. Noradrenergic and
      adrenergic projections from the medulla to the CG may play an important role in a
      variety of autonomic, sensory and behavioral processes.

PMID- 1371781
TI  - Cerebellar nuclei and the nucleocortical projections in the rat: retrograde
      tracing coupled to GABA and glutamate immunohistochemistry.
AB  - The amino acids GABA and glutamate (Glu) are thought to be the principal
      substances in the central nervous system responsible for neuronal inhibition and
      excitation. Their distributions among the different neurons in a defined pathway
      may thus be indicative of the contributions of the cells to pathway function.
      Examples of such neurons are those of the cerebellar nuclei which, while
      regulating output from the Purkinje cells of the cerebellar cortex, are also
      found to project back to the cerebellar cortex. Immunohistochemical experiments
      were done to identify GABA and glutamate (Glu) containing cells in the adult rat
      cerebellar nuclei. Consecutive semithin and serial vibratome sections were
      incubated with antisera raised in rabbit against GABA and Glu. In semithin
      sections, only small neurons were intensely GABA immunoreactive (GABA-IR)
      (31.7%), and the majority (80.5%) were Glu immunoreactive (Glu-IR) of different
      sizes. Consistent with Glu being a metabolic precursor for GABA, 75.4% of the
      GABA-IR population colocalized Glu. In vibratome sections GABA-IR neurons showed
      some local differences in number, whereas the Glu-IR were uniformly distributed
      in the three nuclei studied. Measured mean diameters for these neurons showed a
      distinct size difference for the GABA- and Glu-IR with little overlap. Cerebellar
      nuclei neurons projecting to the cortex (nucleocortical neurons, NCN) were
      identified by locally preinjecting the retrograde transported WGA-apoHRP
      colloidal gold complex in the cerebellar cortex. Vibratome sections of these
      cerebellar were silver intensified for the retrograde tracer and double labeled
      for GABA and Glu. Of the total number of identified NCN, 8.7% were GABA-IR (10
      animals) and 47.7% Glu-IR (5 animals). Many retrograde labeled NCN in the core of
      the thick sections were immunonegative for both amino acids due to poor antibody
      penetration, thus underestimating the proportions of cells containing GABA and
      Glu. The size distributions for the GABA-IR and Glu-IR NCN were similar to those
      measured in non-retrograde labeled nuclei in thick sections. The conclusions
      reached are that GABA-IR neurons of the cerebellar nuclei, including the NCN, use
      GABA as the presumed inhibitory neurotransmitter and that Glu-IR neurons may use
      Glu or another excitatory neurotransmitter.

PMID- 1371782
TI  - Interconnections between the primate cerebellum and midbrain near-response
      regions.
AB  - The goal of this study was to determine the pattern of the connections between
      the midbrain and cerebellum that may play a role in the modulation of the near
      response in the macaque. Injection of the retrograde tracer wheat germ agglutinin
      conjugated horseradish peroxidase (WGA-HRP) into the physiologically identified
      midbrain near-response region, which includes the supraoculomotor area, labelled
      cells throughout the deep cerebellar nuclei. However, labelled cells were
      particularly concentrated in the ventrolateral corner of the contralateral
      posterior interposed nucleus and in the contralateral and, to a lesser extent,
      the ipsilateral fastigial nuclei. Subsequently, injections of WGA-HRP were used
      to define the midbrain terminations of the deep cerebellar nuclei. Fastigial
      nucleus injections labelled terminals in a band along the border between the
      oculomotor nucleus and the supraoculomotor area that included the Edinger
      Westphal nucleus. Injections of the posterior interposed nucleus labelled
      terminals in the portion of the supraoculomotor area dorsal to the fastigial
      projection and did not involve the Edinger-Westphal nucleus. In both cases, the
      terminal label was primarily found contralaterally. In contrast, retrogradely
      labelled cells were primarily found ipsilaterally within the supraoculomotor area
      following cerebellar injections. Retrogradely labelled cells projecting to the
      deep nuclei were also found bilaterally in the anteromedian nucleus, along with
      sparse terminal label. Taken as a whole, these results demonstrate the presence
      of a highly specific pattern of labelling in the supraoculomotor area, which may
      indicate that the posterior interposed nucleus and the fastigial nucleus play
      different roles in the control of the near-response. Alternatively, these
      projections may subserve other functions, such as modulating the pupillary light
      reflex. The fact that the projection from the deep nuclei is primarily
      contralateral, while the supraoculomotor projection to the deep nuclei is
      primarily ipsilateral, suggests that this may not be a simple feedback system,
      but may instead be involved in balancing the gains in the two eyes. In sum,
      physiological experiments have indicated the presence of near-response neurons in
      the midbrain supraoculomotor area and have indicated that the cerebellum may play
      a role in modulating the components of the near-response, as well as activity in
      the intrinsic eye muscles. The present experiments suggest a pattern of
      connections that might subserve this cerebellar modulation.

PMID- 1371783
TI  - Ly-1 (CD5), a membrane glycoprotein of mouse T lymphocytes and a subset of B
      cells, is a natural ligand of the B cell surface protein Lyb-2 (CD72).
AB  - CD5 is a 67-kDa glycoprotein expressed on the cell surface membrane of all T
      lymphocytes and on a small proportion of B lymphocytes. The physiologic role of
      this Ag is still unknown. Structural and functional studies of CD5 suggest that
      it might act as a receptor for a positive signal. CD5-specific mAb augment CD3-
      or mitogen-induced T cell proliferation, IL-2 secretion, and IL-2R expression and
      induce a rise in intracellular [Ca2+]. In this report, we describe the
      purification of mouse CD5 protein (mCD5) and its use as a probe to search for the
      ligand of CD5. We demonstrate that mCD5 specifically interacts with the mouse B
      cell differentiation Ag CD72/Lyb-2. Three serologically defined allelic forms of
      mouse CD72/Lyb-2 can all interact with mCD5. We further show that mCD5 can
      interact with human CD72/Lyb-2, and similarly, that human CD5 can interact with
      mouse CD72/Lyb-2. These studies may have major implications for the mechanisms of
      T-B cell communication.

PMID- 1371784
TI  - Broad recognition of cytotoxic T cell epitopes from the HIV-1 envelope protein
      with multiple class I histocompatibility molecules.
AB  - A few cases have been described of antigenic determinants that are broadly
      presented by multiple class II MHC molecules, especially murine I-E or human DR,
      in which polymorphism is limited to the beta chain, and the alpha chain is
      conserved. However, no similar cases have been studied for presentation by class
      I MHC molecules. Because both domains of the MHC peptide binding site are
      polymorphic in class I molecules, exploring permissiveness in class I
      presentation would be of interest, and also such broadly presented antigenic
      determinants would clearly be useful for vaccine development. We had defined an
      immunodominant determinant, P18, of the HIV-1 gp160 envelope protein recognized
      by human and murine CTL. To determine the range of class I MHC molecules that
      could present this peptide and to determine whether two HIV-1 gp160 Th cell
      determinants, T1 and HP53, could also be presented by class I MHC molecules, we
      attempted to generate CTL specific for these three peptides in 10 strains of B10
      congenic mice, representing 10 MHC types, and BALB/c mice. P18 was presented by
      at least four different class I MHC molecules from independent haplotypes (H-2d,
      p, u, and q to CD8+ CTL. In H-2d and H-2q the presentation was mapped to the D
      end class I molecule, and for Dd, a requirement for both the alpha 1 and alpha 2
      domains of Dd, not Ld, was found. HP53 was also presented by the same four
      different class I MHC molecules to CD8+ CTL although at higher concentrations. T1
      was presented by class I molecules in three different strains of distinct MHC
      types (B10.M, H-2f; B10.A, H-2a; and B10, H-2b) to CTL. The CTL specific for P18
      and HP53 were shown to be CD8+ and CD4- and to kill targets expressing
      endogenously synthesized whole gp160 as well as targets pulsed with the
      corresponding peptide. To compare the site within each peptide presented by the
      different class I molecules, we used overlapping and substituted peptides and
      found that the critical regions of each peptide are the similar for all four MHC
      molecules. Thus, antigenic sites are broadly or permissively presented by class I
      MHC molecules even without a nonpolymorphic domain as found in DR and I-E, and
      these sequences may be of broad usefulness in a synthetic vaccine.

PMID- 1371785
TI  - Characterization of the immune response to a secondary encephalitogenic epitope
      of basic protein in Lewis rats. I. T cell receptor peptide regulation of T cell
      clones expressing cross-reactive V beta genes.
AB  - In Lewis rats, immunization with myelin basic protein induces two distinct
      encephalitogenic T cell populations, those responding to the immunodominant 72-89
      epitope and those specific for a secondary epitope including residues 87-99. The
      72-89 specific T cells were I-A restricted and preferentially expressed V beta
      8.2 in their TCR. To determine the fine specificity, MHC restriction, and TCR V
      beta gene use in T cells reactive to the secondary epitope, we characterized 23 T
      cell clones from the lymph nodes (LN) and spinal cords (SC) of rats immunized
      with either whole basic protein or synthetic peptides S85-99 and S87-99 that were
      found to be functionally similar. The S85-99/S87-99 specific clones from LN and
      SC were all encephalitogenic despite differences in recognition of intact basic
      protein and class II MHC restriction. Unlike LN clones that overexpressed V beta
      8 (46%+) and V beta 6 (31%+), however, SC clones were strongly biased (86%+) in
      their expression of V beta 6. This V gene bias raised the possibility of TCR
      peptide therapy using V beta 6 peptides. The V beta 6 sequence was similar to V
      beta 8.2 in the CDR2 region, and the corresponding peptides from this region were
      found to be cross-reactive in vivo. Moreover, both peptides were effective in the
      treatment of EAE induced with either S85-99, biased in V beta 6+ and V beta 8+ T
      cells, or guinea pig basic protein, biased only in V beta 8+ T cells. These data
      demonstrate the presence of common immunogenic epitopes among subsets of TCR V
      region gene families that possess important regulatory activity on effector T
      cell function.

PMID- 1371786
TI  - Characterization of the immune response to a secondary encephalitogenic epitope
      of basic protein in Lewis rats. II. Biased T cell receptor V beta expression
      predominates in spinal cord infiltrating T cells.
AB  - The immune response of Lewis rat lymph node T cells to guinea pig myelin basic
      protein (GP-BP) in experimental allergic encephalomyelitis is directed primarily
      against a region of basic protein encompassed by residues 72-89. T cells that
      respond to this epitope are restricted by the RT1.B class II molecule of the MHC
      and use V beta 8.2 exclusively in their TCR. A second region of GP-BP, residues
      87-99, also induces experimental allergic encephalomyelitis in Lewis rats but
      this response is restricted primarily by RT1.D. Elsewhere we describe the
      biologic characteristics of T cell clones responding to the synthetic peptide,
      s87-99, and to a related peptide, s85-99. We present a detailed analysis of TCR V
      beta gene expression among these clones, derived from the lymph node and spinal
      cord of immunized animals, and among spinal cord derived T cell clones reactive
      to GP-BP 72-89. We find that spinal cord-derived clones, reactive to s85-99 and
      to s87-99, use V beta 6 predominantly. In contrast, T cell clones derived from
      lymph nodes and reactive to the same peptides express multiple V beta genes
      including V beta 6. This difference in heterogeneity of V beta usage at the
      clonal level is also seen in T cell lines derived from spinal cord and immune
      lymph node. DNA sequence comparison of the CDR3 regions in V beta 6+ spinal cord
      clones revealed a conserved amino acid motif also found in the majority of V beta
      6 sequences from the spinal cord anti-s85-99 line. Although V beta 6 was
      expressed in some lymph node-derived clones, only one contained a CDR3 region
      similar to that seen in spinal cord isolates. All spinal cord-derived T cell
      clones reactive to GP-BP 72-89 used V beta 8.2 and most (five of six) contained
      the AspSer residues in CDR3 previously shown to be associated with V beta 8.2
      receptors expressed by the majority of lymph node T cells responding to GP-BP 72
      89. These data indicate that TCR V beta usage in peripheral T cells responding to
      an autoantigen does not always predict the V beta usage among T cells at the site
      of an autoimmune attack. Possible explantations for the relative homogeneity in
      TCR V beta expression seen in T cell clones derived from the spinal cord are
      discussed.

PMID- 1371787
TI  - Recombinant oncostatin M stimulates the production of acute phase proteins in
      HepG2 cells and rat primary hepatocytes in vitro.
AB  - Acute inflammation is characterized by increased liver output of acute phase
      proteins (APP). Several cytokines including IL-6, leukemia inhibitory factor, and
      IL-11 are capable of stimulating APP synthesis by hepatocytes and hepatoma cells.
      We have tested the activity of a separate and unique cytokine oncostatin M (OM)
      and have found potent APP-inducing activity of human recombinant OM on
      hepatocytes. OM acted in a dose-dependent fashion (ED50 5 to 10 ng/ml) in
      stimulating APP synthesis in human HepG2 cells, rat H35 cells, and primary rat
      hepatocyte cultures, but not human Hep3B cells. Human OM induced equivalent to or
      greater responses than IL-6 in HepG2 cells, however, it was less effective than
      human IL-6 in stimulating rat cells. Northern analysis showed that OM stimulated
      mRNA levels of haptoglobin and alpha 1-antichymotrypsin in HepG2 cells. OM
      induced CAT activity in HepG2 cells transfected with CAT constructs containing IL
      6-responsive elements, suggesting that OM induces transcription of native
      proteins through mechanisms involving IL-6-responsive element-like sequences in
      gene promoters. OM was also shown to act additively with IL-6 or leukemia
      inhibitory factor and synergistically with glucocorticoid or IL-1 in the
      induction of specific APP. These results suggest that OM plays a role as a
      mediator of APP synthesis in inflammatory responses.

PMID- 1371789
TI  - Molecular heterogeneity of Fc alpha receptors detected by receptor-specific
      monoclonal antibodies.
AB  - Fc alpha receptors (Fc alpha R) were isolated from a human monocytic cell line
      and used to raise four mAb with receptor specificity. The antibodies were used to
      identify the types of white blood cells that express Fc alpha R and the molecular
      heterogeneity of the receptor molecules. Nonpolymorphic epitopes, outside of the
      Fc alpha-binding site, were recognized only on blood cells of granulocyte and
      monocyte/macrophage lineages. The molecules identified, both by the antibodies
      and by the IgA ligand, were glycoproteins ranging in relative molecular mass from
      55 to 75 kDa. However, one antibody detected a subpopulation of Fc alpha R
      molecules characterized by relatively restricted size heterogeneity. A complex
      glycosylation pattern was revealed by the resolution of discrete 32- and 36-kDa
      molecular species after removal of N-linked oligosaccharides and by evidence for
      O-linked carbohydrate moieties on at least a portion of the Fc alpha R molecules.
      In biosynthetic studies, all four anti-Fc alpha R antibodies and the IgA ligand
      bound a single 32-kDa core protein present in tunicamycin-treated cells, and the
      exceptional antibody again recognized molecules with relatively restricted
      glycosylation in the nontreated cells. These antibodies and native IgA ligands
      thus provide complementary reagents for definition of the complex structure and
      function of Fc alpha R in systemic IgA antibody responses.

PMID- 1371788
TI  - Gangliosides suppress tumor necrosis factor production in human monocytes.
AB  - Both normal and malignant cells contain gangliosides as important cell membrane
      constituents that, after being shed, may influence cells of the immune system. We
      have studied the impact of gangliosides on the expression of TNF in blood
      monocytes and in the monocytic cell line Mono Mac 6. Although under standard
      culture conditions, bovine brain gangliosides (100 micrograms/ml) suppressed LPS
      stimulated TNF production 5-fold in PBMC and 10-fold in Mono Mac 6 cells,
      suppression was more efficient under serum-free conditions. Looking at highly
      purified gangliosides, GD3, GD1a, GM3, GM2, and GM1 were all effective in
      reducing TNF production in PBMC, and in Mono Mac 6 by factor 10 to 50. The
      suppressive activity was lost in molecules, lacking the sugar moiety or the lipid
      moiety. Gangliosides appear to act at an early step of activation in that TNF
      transcripts were reduced and the mobilization of the nuclear factor kappa B was
      blocked. Furthermore, in time kinetics, gangliosides were effective for up to 30
      min after addition of LPS, but not thereafter. However, the expression of the
      CD14 Ag, a receptor molecule for LPS-LPS binding protein complexes, was
      unaffected by gangliosides. Finally, when using Staphylococcus aureus or platelet
      activating factor as a stimulus, gangliosides were able to suppress TNF
      production in Mono Mac 6 cells by factor 5 to 10, as well. On the other hand,
      phorbol ester-induced production of O2- was similar in cells treated with and
      without gangliosides. Taken together, our data demonstrate that TNF gene
      expression in monocytes induced by different types of stimuli can be blocked by
      gangliosides at an early step of signal transduction.

PMID- 1371790
TI  - Association of human lymph node homing receptor (Leu 8) with the TCR/CD3 complex.
AB  - Cross-linking of the human homologue of the murine MEL-14 lymph node homing
      receptor (Selectin-1, LECAM-1, Leu 8) on both T and B cells results in
      modification of cell function. To investigate this phenomenon, we performed
      studies to determine if the Leu 8 molecule influences T cell activation via the
      TCR/CD3 complex. In initial studies, we treated T cells with immobilized anti-CD3
      (OKT3 mAb) in the presence or absence of immobilized Leu 8 mAb. We found that
      although Leu 8 mAb alone had no effect on T cell proliferation, this antibody
      markedly augmented immobilized OKT3 mAb-induced proliferation. In further
      studies, we immunoprecipitated surface radioiodinated T cell lysates with OKT3
      and Leu 8 mAb to determine if molecules in the TCR/CD3 complex associate with Leu
      8 molecules. Although Leu 8 mAb immunoprecipitated only a single protein of
      approximately 80 kDa from T cell lysates treated with Nonidet P-40 under reducing
      condition, it coimmunoprecipitated additional proteins of 48, 42, 28, 24, and 22
      kDa from T cell lysates treated with 3-[(3-cholamidopropyl)-dimethylammonio]-1
      propanesulfonate. These additional proteins were identified as the alpha-, beta-,
      gamma-, delta-, and epsilon-chains of the TCR/CD3 complex by one-dimensional and
      two-dimensional diagonal SDS-PAGE. Densitometric scanning showed that, on
      average, 18% of the TCR/CD3 complex associates with Leu 8. In a final study, we
      showed by immunoblotting analysis using anti-zeta peptide antibody that Leu 8 mAb
      coimmunoprecipitates the zeta-chain of CD3. These results indicate that the human
      lymph node homing receptor homologue (Leu 8) participates in the activation of T
      cells, probably via its association with the TCR/CD3 complex.

PMID- 1371791
TI  - Immunoreactivity of a 10-kDa antigen of Mycobacterium tuberculosis.
AB  - Identification of Ag of Mycobacterium tuberculosis recognized by T cells is
      essential to understanding the pathogenesis of tuberculosis and mechanism(s) of
      resistance to infection. Previous studies evaluating the immunoreactivity of
      nitrocellulose transfers of M. tuberculosis Ag separated by SDS-PAGE indicated
      that a high proportion of M. tuberculosis-reactive T cell lines proliferate in
      response to a 10-kDa Ag. We therefore purified this Ag from M. tuberculosis
      culture filtrates and evaluated its immunoreactivity in patients with tuberculous
      infection. Proliferative responses of PBMC to the 10-kDa Ag were similar to those
      induced by whole M. tuberculosis and greater than those elicited by other
      proteins isolated from culture filtrate. Furthermore, in patients with
      tuberculous pleuritis, proliferative responses to the 10-kDa Ag were higher in
      pleural fluid mononuclear cells than in PBMC, indicating that T cell reactivity
      to this Ag is enhanced at the site of disease. The first 15 amino acids of the 10
      kDa Ag were identical to those defined previously for Bacillus Calmette-Guerin-a
      (BCG-a), and a T cell clone recognized the 10-kDa Ag and a peptide of BCG-a,
      indicating that the 10-kDa Ag corresponds to BCG-a. This Ag elicited IFN-gamma
      production by pleural fluid mononuclear cells and by PBMC from healthy tuberculin
      reactors, suggesting that the 10-kDa Ag can enhance macrophage activation and
      resistance to mycobacterial infection. Our findings indicate that the 10-kDa Ag
      of M. tuberculosis is highly immunoreactive and should be evaluated for its
      capacity to elicit protective immunity.

PMID- 1371792
TI  - Regions of the CD4 molecule not involved in virus binding or syncytia formation
      are required for HIV-1 infection of lymphocytes.
AB  - Cell surface-expressed CD4 binds to the envelope glycoprotein of HIV-1 and
      mediates syncytia formation through interacting with membrane expressed HIV-1
      gp120. Further possible roles of the CD4 molecule in the process of cell
      infection by HIV-1 remain poorly understood. In our study we describe two mAb
      that recognize the V3/V4 domain of the CD4 molecule. Although these mAb do not
      inhibit gp120-CD4 binding or HIV-1-induced syncytia formation, they inhibit HIV-1
      infection of human PBL. These findings suggest that discrete, definable domains
      of the CD4 molecule may be involved in interactions after HIV-1 envelope binding
      that lead to virus entry into the cell.

PMID- 1371794
TI  - Use of recombinant fusion proteins for generation and rapid characterization of
      monoclonal antibodies. Application to the Kunitz domain of human beta amyloid
      precursor protein.
AB  - Production of peptides by recombinant DNA techniques is an efficient alternative
      to chemical synthesis of peptides. Proteins and peptides produced by recombinant
      DNA methods in E. coli are routinely used as antigens for the production of
      antibodies. However, most small peptides are rapidly degraded within the E. coli
      cell, and therefore, must initially be expressed as components of larger, more
      stable fusion proteins. The peptide of interest must be cleaved from the fusion
      protein, and purified prior to immunization to eliminate epitopes contributed by
      the fusion partner. We have now established methods for the production and
      characterization of monoclonal antibodies using partially purified, uncleaved
      fusion proteins. We have also described a method for efficient production and
      detection of the fusion protein, an EIA for rapid differential screening of
      hybridoma supernatants, and a strategy for epitope mapping of the antibodies.
      These methods have been applied to the production and characterization of
      monoclonal antibodies specific for a 75-amino-acid internal segment of the
      Alzheimer amyloid precursor protein, and should be applicable to a wide variety
      of other peptides and proteins.

PMID- 1371793
TI  - Mouse genotype affects inducible expression of cytokine genes.
AB  - The levels of circulating IFN in mice infected with Newcastle disease virus (NDV)
      are regulated by the If-1 locus. In this study we show that in NDV-infected
      C57BL/6 mice, which carry the If-1h allele and produce high levels of IFN, high
      levels of both IFN-alpha and -beta mRNA can be detected in the spleen. In
      contrast, only very low levels of IFN mRNA could be detected in spleens of
      infected BALB/c mice containing the If-1l allele and producing low levels of IFN
      or in B6.C-H28c mice that are congenic for the If-1l allele. The relative levels
      of all individual IFN-alpha 1, alpha 4, and alpha 6 mRNA in spleens of infected
      BALB/c were lower than in spleens of infected C57BL/6 mice, indicating that the
      If-1 locus affects the expression of all IFN-alpha subtypes and is not associated
      with the deletion or inactivation of a specific IFN gene. The relative levels of
      IFN regulatory factor-1 mRNA in infected mice carrying the If-1l and If-1h loci
      were comparable, suggesting that the If-1 regulation is not associated with the
      altered expression of the IFN regulatory factor-1 gene. Quantitative difference
      in the expression of IFN-alpha and -beta genes was also observed in in vitro
      infected peritoneal macrophages isolated from either C57BL/6 or BALB/c mice. A
      surprise finding was that the If-1 locus also affected the NDV-induced expression
      of two other cytokine genes, TNF-alpha and IL-6. Priming of the macrophage
      cultures with murine IFN enhanced the expression of all cytokine genes, and the
      relative levels of IFN, TNF-alpha, and IL-6 mRNA induced by NDV in macrophages
      derived from C57BL/6 and BALB/c mice were comparable. We propose that the If-1
      locus affects the early stages of a signal transduction pathway which are common
      to the virus-mediated induction of IFN, TNF-alpha, and IL-6 genes.

PMID- 1371795
TI  - Generation of species-specific, rat monoclonal antibodies that bind to the kappa
      chain of mouse immunoglobulin.
AB  - Large numbers of mouse monoclonal antibodies (MAbs) with exquisite binding
      specificities have become available. However the study of these primary
      antibodies in biological fluids by second, anti-mouse antibody techniques, has
      been confounded by the large quantity of other animal immunoglobulin which is
      often present in these fluids. To overcome this problem, we have derived high
      affinity rat MAbs which bind specifically to the antigen binding fragments (Fab)
      of mouse antibody and display minimal or no crossreactivity with human or rabbit
      immunoglobulin at the concentrations which are usually found in plasma.
      Equilibrium binding studies demonstrated that these antibodies had binding
      affinity constants for mouse Fab that ranged from 4.3 x 10(8) to 4.1 x 10(9) M-1.
      All of these rat MAbs bound to the kappa chain of mouse immunoglobulin, though
      competition binding studies amongst these MAbs indicated that they probably
      recognized three different epitopes. Because of their specificity and affinity,
      these rat anti-mouse kappa MAbs may be useful in a wide variety of experimental
      biological systems both in vitro and in vivo.

PMID- 1371796
TI  - A rapid staining procedure for two-color analysis of lymphocyte antigen
      expression.
AB  - Two color immunofluorescence analysis of lymphocyte cell surface antigen
      expression using an unconjugated plus a biotinylated monoclonal antibody (mAb)
      requires four incubation steps: (1) unconjugated mAb; (2) fluorochrome-labelled
      goat anti-mouse Ig; (3) biotinylated mAb; (4) fluorochrome-labelled avidin or
      streptavidin. We describe a time-saving modification of this procedure which
      requires only two incubation steps: (1) simultaneous unconjugated and
      biotinylated mAbs; (2) fluorochrome-labelled avidin/streptavidin followed by
      fluorochrome-labelled goat anti-mouse Ig. The slightly delayed (5 min) addition
      of the goat anti-mouse Ig prevents it from binding to the mAb which has already
      interacted with avidin/streptavidin. Both procedures yield identical results with
      a variety of different mAbs.

PMID- 1371797
TI  - Species differentiation of mycoplasmas by EF-Tu specific monoclonal antibodies.
AB  - Ten mouse hybridoma cell lines producing IgG monoclonal antibodies to mycoplasmal
      elongation factor Tu (EF-Tu) were established. These mAbs showed different
      degrees of cross-reactivity between mollicutes and even other bacteria. This
      finding, indicating protein structure diversities of pan bacterial EF-Tu should
      permit species differentiation of mycoplasmas by epitope pattern analysis of a
      single protein. Epitope patterns of 23 mollicute type strains and of 40 M.
      hominis isolates were determined by ELISA. All M. hominis patterns were found to
      be closely related whereas intrageneric patterns differed in a species specific
      manner.

PMID- 1371798
TI  - [A study on the proliferation of the uterine endometrium].
AB  - A proliferative activity study of the endometrium was evaluated in three
      different parts by means of an immunohistochemical approach and flow cytometry
      (FCM). The materials were 29 cases of hysterectomies due to uterine myoma. Twenty
      one cases were in the proliferative phase, and 8 cases were in the secretory
      phase. The three parts of the endometrium obtained from the upper, middle and
      lower part of the uterine body were investigated by an immunohistochemical
      technique with Ki-67 and anti-DNA polymerase alpha antibody. Single staining with
      Propidium Iodide (PI) was used for cell cycle analysis in FCM. RESULTS: (1) The
      rate of positive Ki-67 cells was 25.9 +/- 6.3% in the upper part, 26.0 +/- 3.3%
      in the middle part, and 25.5 +/- 5.8% in the lower part. And the rate of positive
      DNA polymerase alpha cell was 27.2 +/- 5.8% in the upper part, 24.0 +/- 2.9% in
      the middle part, and 24.8 +/- 4.0% in the lower part. The growth potential of
      each part was not significant. (2) FCM did not detect a significant difference
      among the three parts of the endometrium in cell cycle analysis. (3) Hematoxylin
      eosin staining showed that the upper part was thicker than the lower part and the
      number of glands in the upper part was more abundant than in the lower part. This
      difference was significant (p less than 0.01). (4) Ki-67 was recognized even in
      the early secretory phase. (5) And each segment of the endometrium proliferated
      evenly, not focussed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371799
TI  - [Immunohistochemical study on keratin of squamous cell carcinoma of the uterine
      cervix].
AB  - An immunohistochemical study of squamous metaplasia (n = 10), dysplasia (n = 18),
      squamous cell carcinoma (n = 48) and 3 cases of adenosquamous carcinoma of the
      uterine cervix with anti-56KD keratin and 68KD keratin antibodies was performed.
      In the cases of squamous metaplasia, there were two types of staining of which
      one type had 56KD positive and 68KD negative and another type had both positive.
      In the cases of dysplasia, there were two types of staining the same as in
      squamous metaplasia. But in the cases of carcinoma in situ (CIS) (n = 25), there
      were three types of staining of which the first type had both 56KD and 68KD
      negative (n = 7), the second type had 56KD positive and 68KD negative (n = 15),
      and the third type had both 56KD and 68KD positive (n = 3). In invasive carcinoma
      (n = 23), there were two types of staining the same as in dysplasia of which one
      type had 56KD positive and 68KD negative (n = 17) and another type had both
      positive (n = 6). The keratin negative cases in CIS showed morphologically
      atypical reserve cell hyperplasia composed of atypical small cells with round
      nuclei and had a small lesion compared with other types. This result suggested
      that keratin negative CIS was an early form of CIS which was keratin positive.
      The results indicating that all dysplasia had 56KD keratin positive and CIS had
      not always 56KD keratin positive suggested that dysplasia was not always a
      precursor lesion of CIS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1371801
TI  - Immunohistochemical evaluation with Ki-67: an application to salivary gland
      tumours.
AB  - Using Ki-67, a monoclonal antibody, the proliferating capacity of 15 salivary
      gland tumours, including nine pleomorphic adenomas, four adenoid cystic
      carcinomas, one mucoepidermoid carcinoma and one acinic cell carcinoma was
      determined immunohistochemically, using normal salivary gland tissue as a
      control. The frequency of Ki-67 positive cells was 4.7 percent in the normal
      salivary gland and one percent in pleomorphic adenomas, whereas the average
      frequency in malignant tumours was 18.3 percent. Among adenoid cystic carcinomas,
      the frequency was related to the morphological type; the solid sub-type had the
      highest frequency of Ki-67-positive cells. As this sub-type is recognized as the
      most aggressive of these tumours, this technique has the potential of providing
      an early indication of the clinical behaviour of a tumour.

PMID- 1371800
TI  - Albuminuria is not an aggravating factor in experimental focal glomerulosclerosis
      and hyalinosis.
AB  - It is widely known that the severity of glomerular sclerosis is proportional to
      the degree and chronicity of proteinuria and that the degenerative changes of
      glomerular epithelial cells that are associated with overflow albuminuria can be
      experimentally induced by the injection of large quantities of heterologous
      albumin. Such evidence suggests that autologous albuminuria per se may have a
      harmful effect on the kidneys. To examine the cause and effect relationship
      between renal lesions and albuminuria, we produced Adriamycin-induced
      experimental focal glomerular sclerosis in Nagase analbuminemic (NA) rats and
      control Sprague-Dawley (SD) rats and observed both the renal functional and
      histologic changes for 20 weeks. At week 4 after injection of Adriamycin
      glomerular epithelial lesions including foot process fusion were similarly
      revealed by an electron microscopic study in both groups in spite of the presence
      of a large difference in the amount of proteinuria (SD rats: 491 +/- 84 mg/day,
      NA rats: 43 +/- 30 mg/day) and albuminuria (SD rats: 383 +/- 73 mg/day, NA rats:
      2 +/- 1 mg/day). At week 20, a light microscopic study showed the same degree of
      glomerular sclerosis and hyalinosis and tubulointerstitial changes associated
      with a decrease in inulin clearance in both groups. The increased glomerular
      accumulation of immunoglobulin M or complement 3 and glomerular trapping of
      aggregated human immunoglobulin G were also similar between the SD and NA groups.
      In summary, renal destruction of Adriamycin-nephropathy was not dependent on the
      degree of albuminuria. These results suggest that albuminuria is not an
      aggravating factor in focal glomerulosclerosis.

PMID- 1371802
TI  - Synergism of interleukin 6 and 1 alpha,25-dihydroxyvitamin D3 in induction of
      myeloid differentiation of human leukemic cell lines.
AB  - Interleukin 6 (IL-6) is a multifunctional cytokine with an important role in
      immunity. We analyzed the effect of recombinant human IL-6 in combination with 1
      alpha,25-dihydroxyvitamin D3 (Vit. D3) on differentiation of the human myeloid
      leukemic cell lines U937 and HL-60 with respect to alterations in antigen
      expression and functional activity. Of a panel of antigens analyzed, only CD11b
      (the alpha chain of CR3), and CD14 (a cell surface protein recognizing the
      lipopolysaccharide-binding protein-lipopolysaccharide complex) had significantly
      increased expression. Expression of ICAM-1 (CD54), a ligand for LFA-1, was also
      found to be enhanced with a concomitant increase of ICAM-1 mRNA levels. Enhanced
      nonspecific esterase levels and induction of respiratory burst activity confirmed
      that cell differentiation was induced. Furthermore, IL-6 and Vit. D3 had a
      profound effect on functional activities, as shown by enhancement of rosetting
      between sheep erythrocytes, sensitized with C3bi (EAC), and either U937 or HL-60
      cells. Also, phorbol myristate acetate-induced homotypic adhesion of U937, which
      is ICAM-1 dependent, was markedly induced by these agents. These results indicate
      an important role of IL-6 and Vit. D3 in myeloid cell function and development.

PMID- 1371803
TI  - Effect of adenosine analogues and cAMP-raising agents on TNF-, GM-CSF-, and
      chemotactic peptide-induced degranulation in single adherent neutrophils.
AB  - Adenosine and adenosine analogues are potent inhibitors of the respiratory burst
      in neutrophils. Most investigators, however, have found little or no effect of
      these compounds on neutrophil degranulation from cytochalasin B-treated
      neutrophils in suspension. We have instead investigated the effect of adenosine
      and 2-chloroadenosine on degranulation in adherent neutrophils in the absence of
      cytochalasin B. Both adenosine and 2-chloroadenosine were effective inhibitors of
      lactoferrin secretion induced by the chemotactic peptide N-formyl-methionine
      leucyl-phenylalanine (fMLP) [50% inhibitory concentration (IC50) of less than 10(
      6) M]. Secretion induced by tumor necrosis factor (TNF) or granulocyte-macrophage
      colony-stimulating factor (GM-CSF) was inhibited only at high concentrations
      (IC50 of approximately 10(-4) M). In the presence of cytochalasin B no inhibitory
      effect of 2-chloroadenosine was seen. The effect of cAMP-raising agents on
      secretion from adherent neutrophils was also investigated. Dibutyryl cAMP at 0.2
      mM reduced secretion in response to fMLP by 50% but did not inhibit TNF- and GM
      CSF-induced degranulation. At a concentration of 2.0 mM dibutyryl cAMP also
      inhibited exocytosis in response to the two cytokines. The phosphodiesterase
      inhibitor 3-isobutyl-1-methylxanthine (IBMX) at 300 microM reduced fMLP-induced
      degranulation, whereas a concentration of 1 mM was required to inhibit TNF- and
      GM-CSF-mediated secretion. The adenylate cyclase activator forskolin (50 microM)
      alone did not inhibit secretion in response to TNF or fMLP. However, in
      combination with IBMX (300 microM), forskolin (50 microM) reduced both TNF- and
      fMLP-induced secretion to less than 10%. PMA-induced exocytosis was unaffected by
      all these agents. In conclusion, adenosine appears to be an effective inhibitor
      of neutrophil granule protein secretion induced by fMLP but only a weak inhibitor
      of exocytosis in response to TNF or GM-CSF. Secretion in response to fMLP was
      also found to be more susceptible to a rise in cAMP than degranulation induced by
      TNF and GM-CSF.

PMID- 1371804
TI  - Effects of deglycosylation of human thyroperoxidase on its enzymatic activity and
      immunoreactivity.
AB  - Thyroid peroxidase (TPO) is a glycoprotein enzyme which catalyses the iodination
      of thyroglobulin and the coupling of iodinated tyrosines. Human TPO (hTPO) is the
      microsomal antigen recognized by the autoantibodies in the serum of patients with
      autoimmune thyroid disease. An active detergent-solubilized immunoaffinity
      purified hTPO was deglycosylated, either by peptide N-glycosidase F (PNGase F) or
      by endo-beta-N-acetylglucosaminidase H (endo H), and the enzymatic activity and
      immunoreactivity of the native and deglycosylated forms were compared.
      Electrophoretic controls and affinoblotting with concanavalin A showed that
      deglycosylation was not total and that it was more pronounced with endo H than
      with PNGase F. The enzymatic activity of hTPO was inhibited by endo H
      deglycosylation, but not by PNGase F deglycosylation; this inhibition was not due
      to aggregation and/or insolubilization of the molecule subsequent to
      deglycosylation. Immunoreactivity was monitored by enzyme-linked immunosorbent
      assay (ELISA) with 13 mouse monoclonal antibodies, rabbit polyclonal antibodies
      and antibodies from serum of patients with Hashimoto's thyroiditis. In contrast
      with enzymatic activity, immunoreactivity was not modified or was slightly
      enhanced (with four monoclonal antibodies) by deglycosylation. The results
      indicate that strong, if not total, deglycosylation induces a modification of the
      tertiary structure of hTPO, which affects the enzymatic site but does not modify
      markedly the epitopes implicated in the recognition of the molecule by the
      antibodies tested.

PMID- 1371805
TI  - Muscle siderosis in AIDS: a marker for macrophage dysfunction?
AB  - We have observed numerous iron granules in muscle fibres, endothelial cells and
      macrophages of muscle biopsy specimens of 21 out of 41 AIDS patients with
      different patterns of muscle involvement. All patients were severely
      immunodepressed. We report on our findings and discuss the mechanism of muscle
      siderosis that may point to deterioration of some functions of macrophages at a
      late stage of HIV infection.

PMID- 1371806
TI  - Cell culture as a tool for the study of poultry skeletal muscle development.
AB  - Postnatal development of skeletal muscle is the responsibility of the myogenic
      satellite cells. Satellite cells, isolated from the pectoralis major muscle of
      young growing tom turkeys, have been cultured in vitro to provide a system for
      studying cellular and hormonal aspects of poultry skeletal muscle development.
      Satellite cell clones derived from primary cultures have been developed so that
      in vitro observations would not be confounded by the presence of nonmyogenic
      cells. Likewise, a serum-free medium that promotes proliferation of the turkey
      satellite cell has been developed to provide a hormonally controlled environment
      for in vitro developmental studies. These two techniques have enabled us to
      examine the following: 1) factors that influence satellite cell proliferation and
      differentiation, 2) the interaction of hormones with cellular receptors, 3)
      secretion of biologically important proteins from cells and 4) the expression of
      genes important to muscle development.

PMID- 1371808
TI  - Metastatic breast carcinoma of the masseter: case report.

PMID- 1371807
TI  - Fetal cleft lip repair in rabbits: histology and role of hyaluronic acid.
AB  - This study examines the histologic and biochemical features of wound healing in a
      cleft lip model in the mid-third-trimester fetal rabbit. At days 1, 2, and 4
      after the procedure, control, unrepaired, and repaired fetal heads were obtained,
      sectioned, and stained for histologic examination. The localization of hyaluronic
      acid in the wound was documented using a cartilage-derived hyaluronic acid
      binding protein. In both repaired and unrepaired wounds, the fetal cleft healed
      without inflammatory cell infiltration or scar formation. Six months after birth,
      the repaired cleft showed complete regeneration of muscle across the wound and
      the collagen fibers were of normal density and orientation. Decreased hyaluronic
      acid deposition was observed in unrepaired clefts as compared with adjacent
      tissue; no such difference was detected in repaired clefts. Our findings support
      the hypothesis that a cleft lip repaired in utero heals without the scarring that
      accompanies postnatal repair. This may explain the lack of maxillary growth
      restriction after in utero cleft lip repair.

PMID- 1371809
TI  - Methodological pitfalls in serum IgG2 level measurements by immunoenzymatic
      assays with monoclonal antibodies.
AB  - Four anti-IgG2 monoclonal antibodies (Mabs) were evaluated for their reactivity
      with purified myeloma IgG2 of different light chain types and Gm allotypes in
      three distinct immunoenzymatic assays (ELISA). The reactivity of three Mabs with
      solid-phase antigens was similar whereas an anti-Fab antibody (clone HP 6114)
      predominantly bound IgG2 kappa. In competitive and immunometric (sandwich type)
      assays, the binding of the two anti-IgG2 Mabs (HP 6014 and HP 6114) reacting with
      epitopes located on the Fab fragment was strongly influenced by the light chain
      type of IgG2 and by other factors (probably including differences in the variable
      regions); the Mab HP 6114 reacted virtually only with IgG2 kappa whereas the Mab
      HP 6014 displayed a much stronger affinity for IgG2 lambda than for IgG2 kappa;
      for both anti-Fab Mabs, important differences were found in their binding to
      individual IgG2 proteins. In addition, the Mab HP 6014 seemed to show a slightly
      better affinity for IgG2 bearing the Gm(23) allotype. These results urge much
      caution in IgG2 level measurement, especially with commercial kits, most of which
      use the Mab 6014 as the single anti-IgG2 reagent.

PMID- 1371810
TI  - Decreased histamine release by luteinizing hormone-releasing hormone antagonists
      obtained upon translocation of the cationic amino acid from position 8 to
      position 7.
AB  - We report analogues of N-Ac-D-Nal-D-Cpa-D-Pal-Ser-Lys(Pic)-D-Lys(Pic)-Leu-Ilys
      Pro-D-Ala- NH2, the parent antagonist (PA), which is a potent antagonist of LHRH.
      To simplify future radioactive labeling we prepared N-Ac-D-Nal-D-Cpa-D-Pal-Ser
      Lys(Pic)-D-Lys(Pic)-Leu-Arg-Pro-D-Ala-NH2 (4), [Arg8]PA, which had good activity
      in the antiovulatory assay (AOA). Other analogues were designed at first by
      substituting with Arg at positions 5, 6, 7, 9, and 10, and Trp or Leu at position
      8. Subsequent analogues were prepared in attempts to improve the AOA of the
      initial ones. Substitutions with Arg9 or Arg10 led to analogues 1-3 with no AOA
      activity at 5 micrograms/rat. However, substitution with Arg7 gave 9,
      [Arg7,Leu8]PA, with significant activity in the AOA at 5 micrograms/rat and
      borderline activity at 2.5 micrograms/rat, and substitution with Ilys7 gave 13,
      [Ilys7,Leu8]PA, with borderline activity at 2 micrograms/rat, both analogues
      showing much weaker activity than PA in the histamine release assay (HRA) and
      therefore being potentially safer. Substitutions with D-Arg6 or Arg5 led to
      analogues with either good AO activity at 5 micrograms/rat (analogue 7) or with
      borderline activity at 5 micrograms/rat (analogue 8), although both were more
      potent than 6 in the HRA. Combinations of Ilys or Arg at positions 7 and 8 led to
      10 and 11, both of which were tested at 2 micrograms/rat and found to have either
      good AO activity (analogue 10) or borderline activity (analogue 11) but
      unsuitably potent in HR. Substitutions using Ilys7 and neutral amino acids at
      position 8 led to 14-17 which were inactive in the AOA. Of great significance is
      the substitution with Arg7 yielding analogue 9, which was much safer in the HRA
      than analogue 4, [Arg8]PA. Analogues 9 and 13, featuring substitutions with the
      Arg7-Leu8 or Ilys7-Leu8 sequences were even safer than PA or 6 in the HRA.
      Analogue 12, [D-Trp3,Tyr5,D-Arg6,Arg7,Leu8]PA, featuring the Arg7-Leu8 sequence,
      had much lower potency in the HRA than [D-Trp3,Tyr5,D-Arg6,Leu7,Arg8]PA, which
      has the normal Leu7-Arg8 sequence. Ilys7 together with neutral amino acids at
      position 8 led to analogues 14-17 which were also very weak (safer) in the HRA,
      with the smaller amino acids Ala8 and Abu8 being the weakest of all analogues
      prepared.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1371811
TI  - Effects of irreversible and reversible cholinesterase inhibitors on single
      acetylcholine-activated channels.
AB  - The use of cholinesterase (CHE) inhibitors provided valuable information about
      the mechanism(s) of neuromuscular transmission, but questions on side effects at
      the level of ACh-activated channels were raised. Patch-clamp recording was used
      to study the effects of prostigmine (PST) and methanesulfonyl fluoride (MSF), a
      reversible and an irreversible cholinesterase inhibitor, respectively, on ACh
      activated channels. We found that these drugs diminish the average dwell time of
      elementary currents from around 5 msec (control) to less than 1 msec in the
      presence of PST (20 microM) or MSF (5 mM) (at room temperature). With MSF the ACh
      activated channel conductance of the most frequently observed amplitude class
      decreased from 45 pS (control) to 30 pS, but not in the presence of PST. In
      control conditions there were also amplitude classes of 60 and 24 pS, with
      probabilities of occurrence less than 10%. In the presence of 1.5 mM MSF, where
      current dwell time was not affected, additional subconductance states of 19 and
      36 pS were observed and may be due to partial blockade of the open channel. We
      conclude that the drug of choice to be used in studies on the role of CHE in the
      neuromuscular transmission is MSF, because at 20 microM PST, where blockade of
      ACh-activated channels is significant, cholinesterase was reported to be
      partially inhibited, whereas at 1 mM MSF it is fully inhibited and the dwell time
      of ACh-activated channels is not affected.

PMID- 1371812
TI  - Fidelity of human immunodeficiency virus type I reverse transcriptase in copying
      natural RNA.
AB  - The in vitro fidelity of reverse transcriptase from human immunodeficiency virus
      type I (HIV-1 RT) upon copying an RNA template was measured using the phi Xam 16
      reversion assay. A phi X174 sequence harboring the amber 16 codon was cloned into
      a transcription vector. RNA obtained from transcription by bacteriophage T7 RNA
      polymerase was used as a template for RNA-directed DNA synthesis by HIV-1 RT. An
      imbalance of dNTP concentrations during the reverse transcription step served to
      distinguish between errors that arose from the transcription step and errors from
      reverse transcription. The frequency of dGTP.U mismatches was determined to be
      1/360, while dGTP.rA mismatches formed at a rate of 1/4600. These are 20-fold and
      sevenfold higher, respectively, than the error rates determined for the same
      sequence with a DNA template. Due to a high background of errors in the RNA
      template originating from the transcription step only upper limits for the
      frequency of three other mismatches can be given. The data indicate that the
      reverse transcription step of the HIV-1 replication cycle contributes
      significantly to the generation of mutant viruses.

PMID- 1371814
TI  - [Relapse of peptic ulcer after quick healing induced by proton pump inhibitors].
AB  - Peptic ulcers treated with a proton pump inhibitor heal more quickly than those
      treated with a histamine H2 receptor antagonist. Although satisfactory healing
      without relapse is desirable in the medical treatment of peptic ulcers, the
      relapse rate after treatment with proton pump inhibitors has not been
      sufficiently studied. Up to now, several reports have suggested that peptic
      ulcers treated with omeprazole recur less frequently than those treated with H2
      antagonists. Our experimental studies on angiogenesis in granulation tissue of
      acetic acid-induced gastric ulcers, gastric mucosal collagen synthesis etc., show
      that H2 antagonists have an inhibitory effect on wound healing, but that proton
      pump inhibitors do not. It is suggested, therefore, that proton pump inhibitors
      may at least have no undesirable effect on the natural history of peptic ulcer.

PMID- 1371815
TI  - [Intracellular killing mechanisms of alveolar macrophages against Mycobacterium
      avium complex].
AB  - To clarify the intracellular killing mechanisms of alveolar macrophages against
      Mycobacterium avium complex, effects of cytokines on O2- and NO2- production from
      normal and BCG-induced alveolar macrophages were studied. Intracellular growth of
      M. avium complex was inhibited in the alveolar macrophages stimulated by TNF, but
      not IFN. Enhancement of O2- production by normal alveolar macrophages stimulated
      by cytokines, was associated with the inhibition of intracellular growth of M.
      avium complex. However, when NO2- production by the alveolar macrophages was
      enhanced by the stimulating of IFN or IFN+TNF, in the presence L-arginine in the
      culture medium, their defense activity against M. avium complex decreased.

PMID- 1371813
TI  - Coexpression of vimentin and keratins by human melanoma tumor cells: correlation
      with invasive and metastatic potential.
AB  - BACKGROUND: Several protein markers, including vimentin, have been used to
      diagnose human melanoma. Because melanoma often has metastasized by the time of
      diagnosis, early markers prognostic for metastatic potential need to be
      identified. Commonly, vimentin is found in mesenchymal cells, and keratins are
      present in epithelial cells, but recent studies report coexpression of vimentin
      and keratin(s) in epithelial and nonepithelial neoplasms, including some
      melanomas. PURPOSE: Our purpose was to determine whether coexpression of vimentin
      and keratin(s) is correlated with tumor cell invasion and metastatic behavior.
      METHODS: We evaluated nine human melanoma cell lines expressing vimentin and
      other markers of aggressive tumor behavior (HMB-45, S-100, HLA-ABC class I and
      HLA-DR class II histocompatibility antigens, and K8 and K18 keratins). Levels of
      K8 and K18 keratins were determined in the highly metastatic C8161 cell line, the
      poorly metastatic A375P line, and the moderately metastatic A375M line. To
      determine whether the presence of keratin affects migratory ability, we altered
      the conformational structure of keratin filaments in C8161 cells by transfection
      with a mutant K18 complementary DNA. We also determined messenger RNA levels of
      human type IV collagenase, an enzyme marker for invasion and metastasis. RESULTS:
      In A375P cells, two-dimensional electrophoresis with Coomassie-stained gels,
      immunoblotting, and immunofluorescence staining showed no detectable levels of K8
      or K18. A375M cells showed low levels of K8 and K18 by Western and Northern
      blotting, with a distinctive fluorescent subpopulation of cells. In comparison,
      K8 and K18 levels in C8161 cells were high in all cells. Type IV collagenase
      messenger RNA levels were lowest in A375P cells and highest in C8161 cells,
      correlating with invasive ability in vitro and metastatic potential in athymic
      nude mice. The transfectant clones C1070-10 and C1070-14 derived from the C8161
      parent line showed dramatic morphological changes, disrupted keratin filaments,
      and decreased invasive and metastatic potential directly correlated with a
      reduction in migratory activity. CONCLUSION: These findings show a correlation
      between the coexpression of vimentin with K8 and K18 keratins and the invasive
      and metastatic behavior of three representative human melanoma cell lines.

PMID- 1371816
TI  - [Recombinant granulocyte colony-stimulating factor as a new effective treatment
      of neutropenia].

PMID- 1371817
TI  - Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on
      platelet recovery after high-dose chemotherapy.
AB  - The haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF;
      filgrastim) substantially shortens the period of severe neutropenia that follows
      high-dose chemotherapy and autologous bone-marrow infusion by stimulating
      granulopoiesis. Filgrastim also increases numbers of circulating progenitor
      cells. We have studied the ability of filgrastim to mobilise peripheral-blood
      progenitor cells and assessed their efficacy when infused after chemotherapy on
      recovery of neutrophil and platelet counts. 17 patients with non-myeloid
      malignant disorders received filgrastim (12 micrograms/kg daily for 6 days) by
      continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors
      in peripheral blood increased a median of 58-fold over pretreatment values, and
      numbers of erythroid progenitors increased a median of 24-fold. Three
      leucapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4)
      granulocyte-macrophage progenitors per kg body weight. After high-dose
      chemotherapy in 14 of the patients (busulphan and cyclophosphamide), these cells
      were used to augment autologous bone-marrow rescue and post-transplant filgrastim
      treatment. Platelet recovery was significantly faster in these patients than in
      controls who received the same treatment apart from the infusion of peripheral
      blood progenitors; the platelet count reached 50 x 10(9)/l a median of 15 days
      after infusion of haemopoietic cells in the study patients compared with 39 days
      in controls (p = 0.0006). The accelerated neutrophil recovery associated with
      filgrastim treatment after chemotherapy was maintained. This method may be widely
      applicable to aid both neutrophil and platelet recovery after high-dose
      chemotherapy; it will allow investigation of peripheral-blood progenitor-cell
      allotransplantation.

PMID- 1371818
TI  - Artificial viral envelopes containing recombinant human immunodeficiency virus
      (HIV) gp160.
AB  - An artificial viral envelope was constructed, resembling the human
      immunodeficiency virus (HIV) envelope with respect to ultrastructure, size,
      phospholipid profile and lipid:cholesterol ratio. Recombinant HIV surface protein
      gp160 was anchored in the outer surface of the envelope membrane using a double
      detergent dialysis. The envelopes remained physically stable for several months.
      Immunolabeling with anti-gp160/41 monoclonal antibody revealed surface insertion
      and availability of gp160 for binding. Cell fusion and cytosolic transfer of the
      encapsulated fluorescent marker FITC-dextran was demonstrated. Flow cytometry
      indicated more efficient transfer of the fluorescent marker to cells which were
      approximately 60% CD4+ (REX-1B), relative to cells which were only approximately
      18% CD4+ (KG-1). However, plain lipid envelopes without gp160 fused very
      efficiently with both cell types, indicating their potential usefulness as
      "fusogenic liposomes". Complete artificial viral envelopes may serve as subunit
      vaccines, and receptor-targeted delivery systems for drugs, toxins and genetic
      constructs.

PMID- 1371819
TI  - Hinge region of human IgG2 protein: conformational studies with monoclonal
      antibodies.
AB  - We previously produced three anti-human IgG2 mAbs with high specificity and found
      that they recognize distinct epitopes in the hinge region and neighboring
      residues in human IgG2: HG2-6A was reactive with the hinge region (Glu216
      Pro230); HG2-56F with the Pro234 residue and HG2-30F with the Val235 residue. In
      this study, we evaluated the reactivities of those three mAbs with human IgG2
      protein under various conditions. The results obtained using HG2-6A mAb indicated
      that the hinge region was concealed in the native form, but exposed after heat
      treatment at 63 degrees C, or chemical treatment with 3 M KSCN, 3 M guanidine,
      30% CH3CN, 8 M urea or acid at pH 2.0 as well as by adsorption onto polystyrene
      beads. The IgG2 hinge region was also exposed after binding to specific antigens.
      The Pro234 residue recognized by HG2-56F mAb was exposed under all conditions
      studied. The neighboring Val235 residue recognized by HG2-30F, however, was
      completely concealed in the native and antigen-bound states. Only treatment with
      3 M guanidine and acid at pH 2.0, or physical adsorption induced conformational
      changes to partially expose the Val235 residue.

PMID- 1371820
TI  - Biochemical characterization of CD26 (dipeptidyl peptidase IV): functional
      comparison of distinct epitopes recognized by various anti-CD26 monoclonal
      antibodies.
AB  - In this paper, we performed further biochemical characterization of the CD26
      antigen, as defined by the mAbs in anti-1F7 and anti-Ta1, in order to clarify the
      observed functional differences among these mAbs. For this purpose, we developed
      a mAb, anti-5F8, which recognizes yet another epitope on the CD26 antigen
      different from that recognized by anti-1F7 and anti-Ta1 and compared their
      respective effect on T cell activation as well as the structures recognized by
      these mAbs. Functionally, anti-5F8 did not exhibit a comitogenic effect on T cell
      activation via the CD3 and CD2 pathways. Peptide mapping studies suggested that
      the 110 kDa molecules precipitated by these mAbs are identical. We showed that
      the 110 kDa CD26 structure on human T cells is composed of a family of
      heterogeneous molecules, as determined by isoelectric focusing studies. In
      addition, we demonstrated that the CD26 antigen has a DPPIV enzyme activity and
      this enzyme activity is found only on the principal basic structure of CD26 but
      not on the additional acidic structures. Biochemical studies also revealed that
      these mAbs recognized distinct epitopes on the CD26 antigen. Pulse-chase studies
      showed the the 1F7 epitope was found on both the immature (100 kDa) and mature
      (110 kDa) forms of the CD26 antigen. On the other hand, the Ta1 and 5F8 epitopes
      were expressed mainly on the mature form of the CD26 antigen. Moreover, anti-IF7
      consistently precipitated an additional 43 kDa molecule in association with the
      principal 110 kDa molecule. Taken together, these data suggested that the
      additional 43 kDa structure or the distinct epitope recognized by anti-IF7 may
      play a role in human T cell activation via the CD3 and CD2 pathways.

PMID- 1371821
TI  - Identification of allergenic epitopes on Der f I, a major allergen of
      Dermatophagoides farinae, using monoclonal antibodies.
AB  - The antigenic and allergenic structure of Der f I, a major allergen of the house
      dust mite Dermatophagoides farinae (Df) was investigated by means of a panel of
      11 selected monoclonal antibodies (mAb) obtained from BALB/c mice immunized with
      purified Der f I. The species specificity of these mAb, tested with Der f I and
      Der p I--the homologous allergen from Dermatophagoides pteronyssinus--was
      generally restricted to Der f I since 10 out of 11 mAb reacted only with this
      allergen. Epitope specificity of the mAb was determined by both competitive
      inhibition and sandwich ELISA experiments. The results indicated the presence of
      at least four non-overlapping, non-repeated antigenic sites on Der f I, which
      were recognized by one or several mAb (sites A, B, C and D). Comparative epitope
      specificity studies between human IgE antibodies and mice mAb were performed, on
      sera and basophils of Df sensitive patients, using different inhibition assays
      (ELISA and histamine release experiments). The degree of inhibition varied
      between the patients and upon the assay design. Most of the mAb tested were found
      to significantly inhibit the binding of human IgE to Der f I (p less than 0.01)
      when compared with Der p I specific mAb as a control. The mAb reacting with site
      A was found to be the most potent inhibitor, presenting a mean inhibition of up
      to 56% in ELISA as well as in histamine release experiments. The results show
      that both human IgE antibodies and mAb can be directed against identical or
      closely related epitopes of Der f I. Therefore anti-Der f I mAb constitute
      immunologic probes in further allergenic epitope and peptide analysis of this
      major mite allergen.

PMID- 1371822
TI  - Epitope mapping of the carcinoembryonic antigen with various related recombinant
      proteins expressed in Chinese hamster ovary cells and 25 distinct monoclonal
      antibodies.
AB  - Antigenic epitopes of carcinoembryonic antigen (CEA) and non-specific cross
      reacting antigen (NCA) were analysed in relation to their domain structures
      [domains N, I (A1-B1), II (A2-B2), III (A3-B3) and M for CEA and domains N, I (A1
      B1), and M for NCA]. We reconstructed cDNAs for CEA-N, CEA-N-I, CEA-N-I-II, CEA-N
      I-II-III-M (CEA-whole), NCA-N, NCA-N-I and NCA-N-I-M (NCA-whole), which were
      expressed in Chinese Hamster Ovary (CHO) cells. The recombinant proteins were
      purified by immunoadsorption and gel filtration. Their mol. wts judged from
      Western blotting were 17,000-26,000 for CEA-N, 70,000 for CEA-N-I, 150,000 for
      CEA-N-I-II, 165,000 for s-CEA-whole which was spontaneously released from cells
      into culture medium, 180,000 for p-CEA-whole which was solubilized with
      phosphatidylinositol specific phospholipase C (PI-PLC) from cells, 18,000-25,000
      for NCA-N, 63,000 for NCA-N-I, and 96,000 for p-NCA-whole which was solubilized
      with PI-PLC from cells. The divergence of the observed mol. wts from those
      calculated from cDNA sequences seems to indicate that these recombinant proteins
      are highly N-glycosylated. By enzyme immunoassays, the immunoreactivities of the
      purified recombinant proteins were tested with 25 distinct anti-CEA monoclonal
      antibodies (MAbs), each representative of 25 different subgroups within five
      groups (Groups 1-5) previously classified by us in terms of the reactivity with
      CEA and CEA-related antigens. Twenty-one MAbs previously shown to react with
      different protein epitopes of the CEA molecule allow to define six groups (A-F)
      of epitopes according to their expression by different domains of the CEA and NCA
      molecules. Among four epitopes common to CEA and NCA, two were found to be
      present on domain N (Group A) and two on domain I (Group B). Among 15 epitopes
      absent from NCA but expressed by CEA and normal fecal antigens (NFAs), four were
      on domain N (Group C), five on domain I (Group D) and six on domain II (Group E).
      Two epitopes were previously described as "CEA distinctive", because they were
      recognized by MAbs reacting with CEA but not with the NFAs. These two epitopes
      (Group F) were found to be expressed by p-CEA-whole but not by s-CEA-whole. The
      latter results suggest that the Group F epitopes are located on a part of the
      domain III close to the anchoring device of the CEA molecule.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1371823
TI  - IgE binding structures of the major house dust mite allergen Der p I.
AB  - The group I allergens Der p I and Der f I are potent allergens of mites from the
      genus Dermatophagoides. IgE radioimmune dot blots and immunoabsorption with
      recombinant peptides have been used to define areas of antigenicity. Four linear
      binding regions comprising residues 15-33, 60-80, 81-94 and 101-111 were found in
      the N terminal domain and one, 155-187, in the C-terminal domain, but direct
      evidence for their discontinuous nature is shown. Firstly, the binding activity
      of residues 60-80 required either C- or N-terminal flanking sequences to express
      reactivity and secondly a discontinuous determinant was directly demonstrated by
      the two non-overlapping peptides 53-99 and 101-154 which significantly cross
      absorbed specificities to one another. This also indicates considerable
      homogeneity in the antibodies recognising these peptides. The IgE binding
      peptides could be located to equivalent residues on the X-ray crystallographic
      structure of the homologous proteins actinidin and papain. The residues 81-94 and
      101-111 which gave strong reactivity were located on a flexible loop connecting
      the domains and represent areas in which synthetic peptides could be expected to
      retain activity.

PMID- 1371824
TI  - New monoclonal antibodies as probes for human cardiac troponin I: epitopic
      analysis with synthetic peptides.
AB  - Forty monoclonal antibodies (MAbs) specific for human cardiac troponin I (TnI)
      were selected to develop a new alternative for specific biological diagnosis of
      acute myocardial infarction. Using an immunoenzymatic sandwich assay, these MAbs
      were employed in the mapping of human cardiac TnI and showed six different
      epitopes. Parts of the TnI peptide sequences were synthesised; the sequences were
      chosen from the published sequences of mammalian TnI. Immunological assays showed
      that 8 out of 40 MAbs recognised a RAYATEPHAK (P2) N-terminus cardiac-specific
      sequence of human TnI. The information obtained from epitopic mapping of TnI and
      the properties of the peptides allowed pairs of MAbs to be selected for the
      development of a future specific TnI assay.

PMID- 1371825
TI  - Collaborative study using the preincubation Salmonella typhimurium mutation assay
      for airborne particulate matter in Japan. A trial to minimize interlaboratory
      variation.
AB  - A collaborative study has been performed over a period of 3 years to develop a
      suitable method for monitoring the mutagenicity of airborne particulate matter.
      The study was organized with 8 laboratories and performed in the following steps:
      (1) selection of a suitable technique for each process involved in the
      mutagenicity monitoring, (2) developing a tentative protocol by combining
      systematically the selected techniques, (3) evaluation of the protocol by intra-
      and inter-laboratory studies, (4) modification of the protocol according to the
      evaluation, and (5) evaluation of the modified protocol by conducting an
      interlaboratory study. We found a suitable method for mutagenicity monitoring of
      particles in the atmosphere. Airborne particles were sampled with a high-volume
      sampler, the samples were stored at -80 degrees C, extracted by sonication using
      dichloromethane, solvent-exchanged, and assayed by the preincubation method using
      Salmonella typhimurium TA98 and TA100. The observed mutagenic activity was
      normalized with that of an internal standard. Round robin tests revealed that the
      method resulted in excellent reproducibility. The coefficient of variation for
      mutagenic activities of airborne particulate samples collected in various
      districts of Japan were in the range of 14.7 +/- 6.6% to 19.6 +/- 4.0% for
      strains TA98 and TA100 with and without metabolic activation. We also found that
      the plate incorporation method was equivalent to the preincubation method for
      airborne particulate extracts.

PMID- 1371826
TI  - Discrimination of aneuploidogens from clastogens by C-banding, DNA and area
      measurements of micronuclei from mouse bone marrow.
AB  - Micronuclei (MN) obtained from mouse bone marrow cells, in vivo exposed to 3
      typical clastogens (procarbazine, azathioprine, ethyl methanesulfonate) and 3
      typical aneuploidogens (vinblastine, tubulazole, colchicine), were examined for C
      band, area and DNA content. C-banding allows a clear discrimination between
      clastogens and aneuploidogens: the clastogens do not exceed 50% C-band-positive
      MN and the aneuploidogens all 3 produce 65-75% C-band-positive MN. Concerning the
      DNA content the percentages of MN containing more DNA than an average chromosome
      (chr) are lower than 12% for the clastogens and 38-60% for the aneuploidogens. As
      far as the area of the MN is concerned the percentages of MN which have a larger
      area than chr are lower than 23% for the clastogens and range from 47% to 71% for
      the aneuploidogens. Additionally 3 other mutagens were studied. Hydroquinone
      induces 43% C-band-positive MN with DNA content far below the content of chr;
      considering the area measurements, however, hydroquinone behaves as an
      aneuploidogen (65% of the MN are larger than chr). Mitomycin C lies between the
      clastogens and the aneuploidogens for all 3 criteria but 5-azacytidine is
      comparable to the model aneuploidogens.

PMID- 1371827
TI  - Micronucleated reticulocyte induction by ethylating agents in mice.
AB  - Six model ethylating agents were tested for clastogenic potency by means of a new
      technique of the micronucleus assay with mouse peripheral blood cells using
      acridine orange (AO)-coated slides, to evaluate the test. The alkylating agents
      were: N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), N-ethyl-N-nitrosourea (ENU),
      diethylsulfate (DES), ethyl methanesulfonate (EMS), epichlorohydrin (ECH) and
      ethylene dibromide (EDB). The animals were given a single intraperitoneal
      injection of the following doses of the chemicals: ENNG and ENU, 25, 50 and 100
      mg/kg; EMS and DES, 100, 200 and 400 mg/kg body weight. For EDB and ECH, the
      doses were 50, 100 and 200 mg/kg, given twice, 24 h apart. Before and after the
      injection, blood samples were taken from the tails at 24-h intervals up to 72 h
      and preparations were made on AO-coated slides. For each dose group, 4 animals
      were used and 1000 reticulocytes were examined per slide for the presence of
      micronuclei. At the optimum induction time of 48 h, ENU induced micronucleated
      reticulocytes (MNRETs) at all 3 doses. ENNG and EMS induced MNRETs significantly
      at 2 dose levels each and DES only at the highest dose. ECH and EDB failed to
      induce MNRETs. On the basis of the dose of chemical needed to double the
      spontaneous frequency, the order of clastogenic potency was ENU greater than ENNG
      greater than EMS greater than DES. The results obtained compared favorably with
      those from other in vivo methods. The present technique proves to be simple,
      flexible and relatively sensitive. Shifts in the optimum induction peak in
      individual animals and by some chemicals can be picked up easily which is
      important when testing weak mutagens and chemicals with an unknown mechanism of
      action.

PMID- 1371828
TI  - Contributions to the design and statistical analysis of in vivo SCE experiments.
AB  - Two issues that arise in the design and statistical analysis of in vivo SCE and
      similar experiments are considered. First, with regard to analysis, the merits of
      various methods of data transformation are explored in depth. The conclusion
      drawn is that common transformations of the type studied here seemingly offer
      little advantage in the assessment of whether a test agent induces SCE in a dose
      related manner. Second, a proposal is made for a method to determine, subject to
      budgetary constraints, the desired numbers of animals/dose group and cells
      scored/animal. The approach advocated also lends itself to discussions weighing
      the gains and losses from possible reductions in the number of animals below the
      'desired' levels.

PMID- 1371829
TI  - Species differences in the genotoxicity of cyclophosphamide and styrene in three
      in vivo assays.
AB  - Species differences in dispositional factors such as distribution, metabolism and
      excretion may often account for species differences in the toxic responses to
      foreign chemicals. In this study we compared the genotoxic responses of
      cyclophosphamide (CP) and styrene (ST) between Porton rats and LACA Swiss mice in
      three in vivo assays (bone marrow micronucleus (MN), sperm morphology (SM) and
      sister-chromatid exchange (SCE) assays). The sensitivities of the three assays
      were compared by the doses of the compounds required to elicit a significant
      genotoxic response. The baseline levels for the MN, SCE and SM assays were 1.1
      1.4 and 1.2-1.3 MNPCEs/1000 PCEs, 0.23-0.24 and 0.20-0.21 SCEs/chromosome, 3.5
      5.7% and 1.6-1.9% abnormal sperm in mice and rats, respectively. CP was a potent
      genotoxin in the MN and SCE assays but weakly genotoxic in the SM assay. At
      comparable doses, the rat was approximately 3-, 2.5- and 1.8-fold more sensitive
      to CP than mice in the MN, SM and SCE assays, respectively. ST produced weak
      genotoxic responses in all assays in mice and only in the SM and SCE assays in
      rats. The mice were more sensitive to ST in the MN and SM assays, while it was
      difficult to compare the species in the SCE assay. For both compounds the
      sensitivity of the three assays, in decreasing order, were SCE greater than MN
      much greater than SM. For CP the relative responses in the Porton rats and LACA
      Swiss mice were qualitatively similar to previous reports. Although the use of
      different strains may explain differences between the studies in the magnitude of
      the responses observed. The results for ST in the rat shows that the choice of
      genotoxic endpoint can determine whether a response is detectable. Moreover, the
      discrepancies between the results for ST in this study and others, suggest that
      as well as using a battery of in vivo tests, it may be prudent to select more
      that one strain or species to fully assess a compound's ability to produce DNA
      damage.

PMID- 1371830
TI  - Improved high bioactivation cross for the wing somatic mutation and recombination
      test in Drosophila melanogaster.
AB  - The two tester strains of the high bioactivation (HB) cross for the wing somatic
      mutation and recombination test (SMART) in Drosophila melanogaster developed by
      Frolich and Wurgler possess high metabolic capacity to activate promutagens.
      These strains contain chromosomes 1 and 2 of the DDT-resistant stock Oregon R(R)
      which exhibits a high constitutive level of cytochrome P450. However, they show
      several disadvantages for routine application, such as disturbed wing hair
      patterns in certain areas of the wing, making spot classification difficult, and
      a delay in development of the larvae. We have established and evaluated an
      improved HB cross (ORR; flr3 females and mwh males) producing ORR heterozygous
      individuals. These develop normally and have a normal, undisturbed wing hair
      pattern while exhibiting high bioactivation. The hybrid larvae of the improved HB
      cross show P450-dependent bioactivation capacity equal to or even slightly higher
      than those of the original HB cross. This was demonstrated by measuring the
      genotoxic activity of the promutagens diethylnitrosamine, 7,12
      dimethylbenz[a]anthracene, N-nitrosopyrrolidine, and urethane. In addition, the
      improved HB cross has a sensitivity to the direct-acting alkylating agent ethyl
      nitrosourea equal to that of the standard cross. The main advantage of the
      improved HB cross is to combine the high bioactivation capacity with the ease of
      scoring the wings using the same criteria as for the standard cross.

PMID- 1371831
TI  - Micronuclei and other nuclear anomalies in buccal smears: methods development.
AB  - Laboratory work aimed at improving the epidemiologic utility of an innovative
      genotoxicity assay is described. The exfoliated cell micronucleus assay involves
      microscopic analysis of epithelial smears to determine the prevalence of
      micronucleation, an indicator of structural or numerical chromosome aberrations.
      While the assay holds promise for the study of epithelial carcinogens, it is
      hampered by the fact that exfoliated cells are moribund and undergo degenerative
      phenomena that can produce extranuclear objects difficult to distinguish from
      classical micronuclei. Modifications in the protocol were assessed in sample
      buccal smears from several study populations: radiotherapy patients, nonusers of
      tobacco, and snuff users. Refinements in micronucleus scoring criteria and the
      inclusion of other nuclear anomalies in the scoring system are proposed. We
      demonstrate that our criteria are successful in detecting excess micronucleation
      in positive controls. We also provide evidence that other nuclear anomalies are
      at least as common as micronucleation and that therefore there is the potential
      for extensive misclassification. Reliability was assessed in duplicate readings.

PMID- 1371832
TI  - Application of an epithelial liver cell line, metabolically competent, for
      mutation studies of promutagens.
AB  - Recently numerous attempts have been made to reduce the use of vertebrate animals
      in laboratory experiments to evaluate general and acute toxicity, mutagenesis and
      teratogenesis of new drugs or chemicals. One common approach is to use
      established, proliferating cell lines that preserve differentiated functions such
      as the competence to metabolize xenobiotics. To this end a continuous Chinese
      hamster epithelial liver cell line (CHEL cells) was established, cultured as used
      for mutagenesis studies. Structurally different promutagens, such as 7,12
      dimethylbenz[a]anthracene (7,12-DMBA), benzo[a]pyrene (B(a)P), aflatoxin B1 (AB1)
      and cyclophosphamide (CP), were used in order to check and validate the test
      system. anti-Chrysene-1,2-diol 3,4-epoxide (CDE) and mitomycin C (MMC) were taken
      as representatives of direct mutagens. The genetic change induced by the mutagens
      was quantified by measuring mutation frequencies at the HGPRT locus. Several
      parameters, such as mutant expression time for each chemical, cell density for
      selection of mutants and enzymatic characterization for HGPRT phenotype, were
      examined to establish the optimal assay conditions. All promutagens analyzed
      significantly affected either the cloning efficiency and/or the mutant frequency
      of CHEL cells after 24 h of exposure. In addition, various enzyme activities
      involved in the metabolism of the promutagens were determined in CHEL cells,
      under the experimental conditions of chemical exposure used in the mutagenesis
      assay. The enzyme activities were compared with those found in uninduced Chinese
      hamster liver.

PMID- 1371833
TI  - Mutagenicity assay for nitroarenes of air pollutants held in leaves of woody
      plants.
AB  - A new method was developed for the detection of mutagenic nitroarenes held in the
      leaves of woody plants using a small amount of leaves. This method consists of
      extraction of mutagen from fresh leaves (15-30 g) by ultrasonication with ethyl
      acetate and purification by elution with benzene on a silica gel column to remove
      such inhibitory components for mutagenesis as chlorophyll. The mutation assay
      uses the new Salmonella typhimurium strains YG1021 (a nitroreductase
      overproducing strain of TA98) and YG1024 (an O-acetyltransferase-overproducing
      strain of TA98), which are very sensitive to some nitroarenes in the absence of
      S9, and standard strain YG1020 (TA98 containing pBR322-Aps) for comparison. This
      method was applied to woody plants growing on various sites in the Tokyo
      metropolitan area and the suburbs. It was shown that the leaves of all woody
      plants tested contained different amounts of mutagens, probably mutagenic
      nitroarenes, depending upon their growing sites.

PMID- 1371834
TI  - Dose-ranging and dose-setting for in vivo genetic toxicology studies.

PMID- 1371835
TI  - Biphenyl and fluorinated derivatives: liver enzyme-mediated mutagenicity detected
      in Salmonella typhimurium and Chinese hamster V79 cells.
AB  - Hepatocarcinogenic polychlorinated and polybrominated biphenyls usually show
      negative results in in vitro mutagenicity assays. Problems in their testing
      result from their low water solubility and their slow rate of metabolism. We
      therefore investigated better soluble model compounds, namely biphenyl and its 3
      possible monofluorinated derivatives. In the direct test, these compounds proved
      to be nonmutagenic in Salmonella typhimurium TA98 and TA100 (reversion to
      histidine prototrophy) and in Chinese hamster V79 cells (acquisition of
      resistance to 6-thioguanine). However, when the exposure was carried out in the
      presence of NADPH-fortified postmitochondrial fraction of liver homogenate from
      Aroclor 1254-treated rats, all 4 compounds showed mutagenic activity in V79
      cells. 3-Fluorobiphenyl produced strong mutagenic effects in S. typhimurium TA100
      as well, whereas the other biphenyls were inactive. In strain TA98, 3- and 4
      fluorobiphenyl showed mutagenic activity. This mutagenicity was enhanced in the
      presence of 1,1,1-trichloropropene 2,3-oxide, an inhibitor of microsomal epoxide
      hydrolase, thus suggesting that epoxides may be active metabolites.

PMID- 1371836
TI  - Differential effect of the amino acid cystine in cultured mammalian and bacterial
      cells exposed to oxidative stress.
AB  - The effect of cystine in the cytotoxic response of cultured Chinese hamster ovary
      and Escherichia coli cells to challenge with hydrogen peroxide has been
      investigated. It was found that this amino acid could either protect or sensitize
      cells, depending on the cellular system. In fact, although a reduction in the
      growth-inhibitory effect of hydrogen peroxide was observed in mammalian cells, a
      marked increase in the susceptibility to oxidative stress was induced by cystine
      in bacteria. None of the amino acid precursors of glutathione, e.g., glutamate,
      glycine or cysteine, afforded protection in the mammalian cell system, whereas
      cysteine, but not glycine or glutamate, markedly sensitized bacteria to hydrogen
      peroxide-induced cell killing. In mammalian cells, methionine, an amino acid
      which is converted to cysteine, was also unable to modify the oxidative response.
      The results presented indicate that cystine displays differential effects in
      oxidatively injured mammalian or bacterial cells and suggest that the mechanism
      whereby the amino acid modulates the lethal action of hydrogen peroxide differs
      in the two cellular systems.

PMID- 1371837
TI  - D and C Red No. 9: genotoxic or non-genotoxic carcinogen?
AB  - The azo-compound, D and C Red No. 9 was assayed for genotoxicity in vivo using
      the rat micronucleus test and the rat ex vivo liver UDS assay. Uniformly negative
      results were obtained in both assays, even though large oral doses were used (2
      g/kg). These results suggest that the tumorigenic effects of this compound in
      rats are mediated through non-genotoxic rather than a genotoxic mechanism.
      Further experiments using additional end-points such as 32P-post-labelling would
      further substantiate this conclusion.

PMID- 1371838
TI  - Irradiated cocoa tested in the wing spot assay in Drosophila melanogaster.

PMID- 1371839
TI  - Sister-chromatid exchange analysis in a rural population of Mexico exposed to
      pesticides.
AB  - Cytogenetic damage was evaluated by means of the analysis of sister-chromatid
      exchange (SCE) in a rural population of Tlaxcala, Mexico, in occupational contact
      with pesticides. We studied 170 men, 94 exposed and 76 not exposed. It was shown
      that SCE followed a normal distribution and Student's t test did not present
      differences between the two groups (P = 0.4). The frequency of SCE was not
      correlated with the duration of exposure of the rural workers (r = -0.06), the
      multiple covariance analysis applied to the data of duration of exposure, tobacco
      intake and alcohol ingestion demonstrated a lack of statistical significance. In
      the exposed people we observed no symptoms provoked by these compounds.

PMID- 1371840
TI  - The correlation between the frequency of micronuclei and specific chromosome
      aberrations in human lymphocytes exposed to microwave radiation in vitro.
AB  - Human whole-blood samples were exposed to continuous microwave radiation,
      frequency 7.7 GHz, power density 0.5, 10 and 30 mW/cm2 for 10, 30 and 60 min. A
      correlation between specific chromosomal aberrations and the incidence of
      micronuclei after in vitro exposure was observed. In all experimental conditions,
      the frequency of all types of chromosomal aberrations was significantly higher
      than in the control samples. In the irradiated samples the presence of dicentric
      and ring chromosomes was established. The incidence of micronuclei was also
      higher in the exposed samples. The results of the structural chromosome
      aberration test and of the micronucleus test were comparatively analyzed. The
      values obtained showed a positive correlation between micronuclei and specific
      chromosomal aberrations (acentric fragments and dicentric chromosomes). The
      results of the study indicate that microwave radiation causes changes in the
      genome of somatic human cells and that the applied tests are equally sensitive
      for the detection of the genotoxicity of microwaves.

PMID- 1371841
TI  - Detection of aneuploidy in male germ cells of mice by means of a meiotic
      micronucleus assay.
AB  - The possibility of using a micronucleus (MN) assay in mouse germ cells for the
      identification of aneuploidogenic agents was evaluated by comparing the pattern
      of effects induced by 4 chemicals with different mechanisms of action
      (adriamycin, ADM; mitomycin C, MMC; chloral hydrate, CH;
      ethylenedinitrilotetraacetic acid, EDTA). The results obtained after treatment of
      spermatocytes at the premeiotic S-phase (preleptotene) indicated that only
      clastogenic agents (ADM and MMC) were able to induce MN at this cell stage.
      Previous data obtained with the same compounds demonstrated by contrast that the
      micronucleus spermatid assay may detect both clastogenic and aneuploidogenic
      effects after treatment of diakinesis/MI/MII cells. Analysis of MN size
      distributions, in the present and previous spermatid samples, revealed that the
      clastogens ADM and MMC produced relatively more small MN than CH and EDTA. These
      data are in agreement with the proposed mechanism of action of the chemicals
      tested.

PMID- 1371842
TI  - Mutagenicity of nitric oxide and its inhibition by antioxidants.
AB  - Nitric oxide (NO) is produced both by macrophages in vivo as a physiological
      response to infection and by a variety of cell types as an intercellular
      messenger. In addition, NO and nitrogen dioxide (NO2) are significant components
      of many combustion processes. The ubiquitous exposure of humans to nitrogen
      oxides (NOx), both endogenously and exogenously, may play a significant role in
      the carcinogenic process due to nitrosation of amines by NOx. We report here that
      exposure to low concentrations of NO, alone or in combination with NO2, results
      in significantly enhanced mutation in Salmonella typhimurium TA1535 using a
      modified Ames Salmonella reversion assay. The observed mutagenicity requires that
      the bacteria be actively dividing at the time of exposure to NO or NO2,
      suggesting that the nitrogen oxides, or their reaction products, function as
      direct-acting mutagens and that the induced lesion is easily repairable by non
      dividing cells. Exposure to NO resulted in a time- and dose-dependent increase in
      the number of revertants approximately proportional to the square of the NO
      concentration from 0 to 20 ppm. NO was a more effective mutagen relative to NO2,
      however, the observed requirement for O2 suggests limited oxidation of NO
      (presumably to NO2) is necessary. Numerous lipid- and aqueous-phase inhibitors of
      nitrosation, as well as a number of other general antioxidants and free-radical
      trapping agents, were examined for their effectiveness in blocking the mutagenic
      effects of NO. The mutagenic activity of NO was most effectively inhibited by
      beta-carotene and tocopherols. BHT, dimethyl sulfoxide and mannitol also blocked
      the mutagenic effects of NOx but appeared less effective than beta-carotene or
      vitamin E, while ascorbate was ineffective as an inhibitor of mutation resulting
      from NO exposure.

PMID- 1371843
TI  - Ozone is not mutagenic in the Tradescantia and tobacco mutagenicity assays.
AB  - Ozone fumigation of a double heterozygous chlorophyll mutant Nicotiana tabacum
      var. xanthi n.c. with concentrations up to 300 nl/l and of a heterozygous
      Tradescantia clone 4430 with concentrations up to 800 nl/l did not increase the
      frequency of somatic mutations above the spontaneous levels. However, ozone
      fumigation at these concentrations led to distinct physiological damage to plant
      tissues.

PMID- 1371844
TI  - The role of the excision and error-prone repair systems in mutagenesis by
      fluorinated quinolones in Salmonella typhimurium.
AB  - Patterns of reversion produced by ciprofloxacin, enoxacin and ofloxacin in
      Salmonella typhimurium strains carrying the hisG428 ochre mutation have been
      studied. These fluorinated quinolones produce a significant increase in reversion
      of this mutation, even when it is located on the chromosome. Nevertheless,
      reversion is higher when the hisG428 mutation is on the multicopy plasmid pAQ1
      than when it is on the chromosome. Reversion of hisG428 induced by fluorinated
      quinolones is abolished both in a uvrB genetic background and in the absence of
      the plasmid pKM101. Therefore, mutagenesis produced by fluorinated quinolones in
      the Salmonella mutagenicity assay is significantly affected by both the excision
      repair and the error-prone repair systems. Furthermore, fluorinated quinolones
      are also detected as moderate mutagens with the base substitution hisG46 mutation
      when both repair systems are functional in the tester strain.

PMID- 1371845
TI  - N-methyl-N'-nitro-N-nitrosoguanidine-induced light emission in Chinese hamster
      cell cultures: correlation with enhancement of chromosomal aberrations.
AB  - N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was found to induce an ultraweak
      photon emission in cultures of Chinese hamster fibroblasts (CHL). Measurements
      suggest that the light emission is due to a reaction between MNNG and cellular
      metabolites. The light emission depended on the concentration of MNNG and was
      oxygen-dependent, disappearing in a nitrogen atmosphere. Superoxide dismutase
      (SOD) or sodium azide decreased the emission intensity. The production of
      chromosomal aberrations in CHL by MNNG was correlated with the light emission
      intensity and was inhibited in the presence of SOD.

PMID- 1371846
TI  - Construction of a umuDC operon substitution mutation in Escherichia coli.
AB  - Using a specialized transducing lambda phage, the umuDC operon of Escherichia
      coli was deleted and replaced with the chloramphenicol acetyltransferase gene.
      The delta (umuDC)595::cat mutation was subsequently transferred by generalized P1
      transduction into a variety of genetic backgrounds. It is concluded that the
      UmuDC proteins, which are normally required for inducible mutagenesis, are not
      essential for cell survival.

PMID- 1371848
TI  - [Developments in the care of cancer patients].

PMID- 1371847
TI  - The movement of fluorescent endocytic tracers in Plasmodium falciparum infected
      erythrocytes.
AB  - The fluorescent lipophilic probe 1,1'-dihexadecyl-3-3'-3-3'-
      tetramethylindocarbocyanine (diIC16) inserted in the red cell surface, functioned
      as a non-exchangeable lipid marker which was not metabolised or toxic in
      plasmodial cultures. Invasion by Plasmodium falciparum resulted in the
      internalisation of the lipid, suggesting the uptake of red cell membrane
      components during parasite entry. The fluorescent lipid was not transported from
      red cell to parasite membranes at subsequent stages of development, but label in
      the erythrocyte-derived parasitophorous vacuole was eventually detected in
      daughter merozoites. Fluorescent dextrans of 10 kDa in the extracellular medium
      were also not internalised during intraerythrocytic parasite growth. The results
      support that with the exception of the invasion step, plasmodial infection does
      not induce endocytosis in the erythrocyte membrane. Despite the lack of
      endocytosis, both D and L stereoisomers of the head group blocked phospholipid
      analogue N-4-nitrobenzo-2-oxa-1,3-diazoledipalmitoyl phosphatidylethanolamine (N
      NBD-PE) inserted in the erythrocyte membrane, were internalised by mature
      infected erythrocytes. Lipid internalisation occurred by a non head group
      dependent parasite mechanism, which could account for the stage-specific uptake
      of phospholipids observed in mature infected erythrocytes. We were unable to
      detect the transport of carbocyanine dyes and N-NBD-PE from intracellular
      parasites back to the erythrocyte membrane. Additionally, the carbocyanine dyes
      were not transferred between adjacent organisms in a double infected red cell.
      The data argue for the absence of bulk membrane lipid transport between
      individual parasites and their host cell bilayer in an infected erythrocyte.

PMID- 1371849
TI  - Increased S100 beta neurotrophic activity in Alzheimer's disease temporal lobe.
AB  - The confirming diagnosis of Alzheimer's disease includes an assessment of the
      concentration of neuritic plaques in the temporal lobe of the brain. The presence
      of abnormal levels of neurotrophic factors in Alzheimer's disease is one possible
      explanation for the increased concentration of aggregates of overgrown neurites
      in the neuritic plaques of Alzheimer's disease. The protein S100 beta, a
      neurotrophic factor produced by astroglia in the brain, induces neurite outgrowth
      in cerebral cortical neurons. The generation of specific S100 beta antibodies,
      the cloning of a full-length cDNA encoding the S100 beta mRNA, and the
      development of a neurite extension assay system for S100 beta allowed testing of
      the hypothesis that Alzheimer's disease S100 beta expression is elevated in brain
      temporal lobe where neuritic plaques are concentrated. The levels of S100 beta
      protein, mRNA, and specific neurotrophic activity were elevated 10-20-fold in
      extracts of temporal lobe from autopsy samples of Alzheimer's disease patients
      compared to those of aged control patients. The cells containing the increased
      S100 beta were reactive astrocytes; the neuritic plaques were surrounded by S100
      beta-containing astrocytes. The elevated levels of S100 beta provides a link
      between the prominent reactive gliosis and neuritic plaque formation in this
      common disease of the elderly and raises the possibility that S100 beta
      contributes to Alzheimer's disease neuropathology.

PMID- 1371850
TI  - Significance of decreased lumbar CSF levels of HVA and 5-HIAA in Alzheimer's
      disease.
AB  - The monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5
      HIAA) and 4-hydroxy-3-methoxy-phenylglycol (HMPG) were determined in lumbar
      cerebrospinal fluid (CSF) of 123 patients with Alzheimer's disease (AD) and 57
      healthy controls. Despite CSF sampling under strictly standardized conditions, a
      wide variability in values among both patients and controls was found, as well as
      fluctuations in repeated samples from individual patients. This suggests that
      several unknown factors influence the lumbar CSF levels of monoamine metabolites.
      The AD group showed significantly lower mean levels of HVA (p less than 0.0001)
      and 5-HIAA (p less than 0.0001) than the control group. A relation between
      severity of disease and HVA was also found. The widespread neurotransmitter
      disturbance in AD, together with the nonspecificity of reduced lumbar HVA and 5
      HIAA levels, suggests that the changes are nonspecific, secondary to the cerebral
      degeneration in AD.

PMID- 1371851
TI  - [Spinal epidural stimulation for central pain caused by spinal cord lesion].
AB  - Epidural spinal cord stimulation was carried out in 4 patients with denervation
      caused by spinal cord lesion, and we reviewed previously reported cases. Initial
      result showed at 1 week in 100% of our cases, but about 1/3 of the cases, even
      those with the same denervation caused by spinal cord lesion, had no pain relief
      at this stage in previously reported cases. In our cases, excellent pain relief
      was gained temporarily, even though the painful area and the spinal cord lesion
      were separated somatotopically in 2 cases (case 3, 4). Temporary success bore no
      relationship to quality and duration of pain. In all cases except case 1, a
      rapidly decreasing effectiveness was noted, and finally no pain relief was gained
      at all after 4, 3 and 5 months, respectively. In case 1 there was persistent pain
      relief estimated at 70-80% after 19 months, only when the spinal cord was
      stimulated. Epidural stimulation also produced sensations in the painful area.
      Spinal cord stimulation would suppress at least the dorsal horn neurons which
      were destroyed by various kinds of diseases. A decline in effectiveness with time
      would occur due to essential causes of the deafferentation pain, such as
      anatomical and regeneration factors.

PMID- 1371852
TI  - [AFP producing gastric cancer manifested by metastasis to the tentorium
      cerebelli; case report and review of the literature].
AB  - We report a case of AFP producing gastric cancer manifested by metastasis to the
      tentorium cerebelli. A 66-year-old male patient was admitted with dysarthria,
      occipital headache and nausea on May 1, 1990. Neurological examination revealed
      signs of increased intracranial pressure and the right-sided cerebellar
      hemispheric signs. CT and MRI showed a round tumor shadow 3cm in diameter, which
      originated in the right-side tentorium cerebelli and grew in the posterior fossa.
      Tumor stains fed by the right tentorial artery were recognized by angiography.
      Serum AFP level was 503.5ng/ml. The patient underwent an operation under general
      anesthesia in the prone position. The tumor was totally removed via the
      suboccipital transtentorial approach. Histological examination revealed AFP
      producing adenocarcinoma. The patient was found to have a gastric cancer after
      neurosurgical operation, and underwent subtotal gastrectomy by surgeons. Serum
      AFP level was 254.5ng/ml after removal of metastatic brain tumor, and 5.0ng/ml
      after subtotal gastrectomy.

PMID- 1371853
TI  - Anticonvulsant role of nigrotectal projection in the maximal electroshock model
      of epilepsy--II. Pathways from substantia nigra pars lateralis and adjacent
      peripeduncular area to the dorsal midbrain.
AB  - Lesion evidence suggests that the superior colliculus is essential for mediating
      the anticonvulsant properties of nigral suppression in the electroshock model of
      epilepsy. However, our companion paper [Redgrave et al. (1991) Neuroscience 46,
      379-390] established that the region of dorsal midbrain where bicuculline was
      most effective in suppressing tonic hindlimb extension did not correspond well
      with the known distribution of nigrotectal terminals. The purpose of the present
      anatomical study was, therefore, to investigate in more detail ventral midbrain
      connections to the dorsal midbrain anticonvulsant zone in rat. Small injections
      (10-20 nl) of a 1% solution of wheatgerm agglutinin conjugated with horseradish
      peroxidase were made specifically into the region of dorsal midbrain where
      bicuculline was maximally effective. Numerous retrogradely labelled cells were
      found in substantia nigra pars lateralis and adjacent peripeduncular area but not
      in substantia nigra pars reticulata. Retrogradely labelled cells were also
      located in ventral zona incerta. When wheatgerm agglutinin-horseradish peroxidase
      injections were made into lateral substantia nigra, a region of anterogradely
      transported reaction product characteristic of nerve terminals was observed in
      the caudolateral deep layers and underlying reticular tissue; this area
      corresponded well to the dorsal midbrain anticonvulsant zone. These data suggest
      that, in the electroshock model of epilepsy, direct connections between
      substantia nigra pars lateralis and adjacent peripeduncular area and the dorsal
      midbrain anticonvulsant zone could be critical for mediating the anticonvulsant
      properties previously attributed to substantia nigra pars reticulata. During the
      course of this study, anterograde projections from substantia nigra pars
      lateralis and adjacent peripeduncular area to both superficial and intermediate
      layers of the ipsilateral superior colliculus were noted. Additional experiments
      using retrograde transport of the fluorescent tracer Fast Blue confirmed these
      projections.

PMID- 1371854
TI  - Serotonin synthesis in adrenochromaffin cells.
AB  - The inter-renal (adrenal) gland of amphibians is composed of chromaffin and
      steroidogenic cells which can interact through a paracrine mode of communication.
      We have previously shown that serotonin is present in secretory granules of frog
      adrenochromaffin cells; concurrently, we have demonstrated that serotonin is a
      potent stimulator of corticosterone and aldosterone secretion by adrenocortical
      cells. The aim of the present study was to determine the origin of the amine
      contained in frog chromaffin cells. Using 3H-labelled tryptophan as a precursor,
      we observed the formation of substantial amounts of serotonin and its metabolite
      5-hydroxyindoleacetic acid by frog inter-renal slices. Newly synthesized
      serotonin was secreted into the incubation medium and the release process was
      enhanced by depolarizing concentrations of KCl. Fluoxetine, and inhibitor of
      serotonin uptake, caused an increase of 3H-labelled serotonin in the incubation
      medium, suggesting that the indoleamine was taken up again by adrenal chromaffin
      cells. The capacity of the frog inter-renal gland to synthesize serotonin was
      also demonstrated by incubating inter-renal slices with non-labelled tryptophan
      or 5-hydroxytryptophan. In these conditions, we observed that the rate of
      synthesis was higher when 5-hydroxytryptophan was used as a a precursor, rather
      than tryptophan. Taken together, these results indicate that chromaffin cells,
      which have the capacity for synthesizing and releasing serotonin, behave like
      authentic serotonergic paraneurons. As far as is known, these data provide the
      first evidence for the occurrence of tryptophan-5-hydroxylase activity within the
      adrenal gland.

PMID- 1371855
TI  - Histochemical mapping of nitric oxide synthase in the rat brain.
AB  - The NADPH-diaphorase histochemical technique provides a simple and robust method
      to stain select populations of neurons throughout the brain. We have recently
      identified the enzyme responsible for this histochemical reaction to be nitric
      oxide synthase. This enzyme is responsible for the calcium-dependent synthesis of
      nitric oxide from arginine. Nitric oxide acts as a novel neural messenger by
      stimulating soluble guanylyl cyclase thereby increasing the levels of cyclic
      guanosine 3',5'-monophosphate in target cells. Thus the NADPH-diaphorase
      histochemical method allows the direct visualization of the neurons which use
      this novel signal transduction pathway. We now describe the detailed distribution
      of this enzyme in the rat brain. Our results suggest a widespread role for the
      nitric oxide-cyclic guanosine monophosphate system in the nervous system.

PMID- 1371856
TI  - Potential- and acetylcholine-activated ionic currents of pheochromocytoma PC12
      cells during incubation with nerve growth factor.
AB  - Pheochromocytoma PC12 cells incubated with and without nerve growth factor were
      investigated using the patch-clamp technique in the whole-cell recording mode,
      and the concentration clamp method in the rat. On the fourth day of incubation
      with nerve growth factor, sodium potential-activated ionic currents appeared in
      the membranes of the most morphologically differentiated cells. At the same
      period a three-fold increase of acetylcholine-activated current density, compared
      with the cells incubated without nerve growth factor, was observed. Thus, the
      qualitative and quantitative changes in membrane properties can be a result of
      metabolic reorganization in PC12 cells induced by nerve growth factor and
      accompanied by morphological differentiation according to neuronal phenotype.

PMID- 1371857
TI  - Study of the topographical distribution of different populations of motoneurons
      within rat's nucleus ambiguus, by means of four different fluorochromes.
AB  - The topographical neuronal distribution within the rat nucleus ambiguus has been
      studied with the simultaneous retrograde labeling technique by means of four
      different fluorochromes injected within the various muscles and/or nerves of the
      oro-pharyngeal region. This technique has permitted the identification of several
      types of neurons along the same coronal plane. Most were motoneurons innervating
      the various muscles of the upper airway, including pharyngeal constrictor,
      stylopharyngeal, intrinsic laryngeal and the upper portion of the esophagus. Some
      neurons may have been preganglionic parasympathetic neurons. No evidence of
      axonal branching of any of the labeled motoneurons or parasympathetic neurons was
      found.

PMID- 1371858
TI  - Injury-induced reduction of acidic fibroblast growth factor levels in the distal
      parts of rat sciatic nerve.
AB  - Acidic fibroblast growth factor (aFGF) level in sciatic nerve after lesioning was
      measured by enzyme immunoassay to determine if aFGF functions as a neurotrophic
      factor like nerve growth factor (NGF). Whereas the NGF level increased in distal
      segments, the aFGF level there decreased after transection or crushing and
      recovered to the original level by 10 weeks after crushing. The amount of aFGF
      mRNA in the sciatic nerve was extremely low to supply the high level of protein
      found in the sciatic nerve. Sympathetic ganglia, dorsal root ganglia, and spinal
      cord, which contain neuronal cell bodies extending their axons into the sciatic
      nerve, showed a greater or similar level of aFGF as sciatic nerve. These results
      imply that aFGF is synthesized in neuronal cell bodies and distributed
      anterogradely into their axons. Difference of injury-induced changes in levels
      between aFGF and NGF suggests distinct mechanisms of the effects elicited from
      these factors on regeneration of the sciatic nerve.

PMID- 1371859
TI  - In vitro interaction between cerebellar astrocytes and granule cells: a putative
      role for nitric oxide.
AB  - In primary cultures of astrocytes and granule cells from neonatal rat cerebellum,
      the activity and function of nitric oxide (NO) synthase were measured by the
      conversion of [3H]arginine to [3H]citrulline and the accumulation of cyclic
      guanosine monophosphate (cGMP), respectively. The glutamate receptor agonist N
      methyl-D-aspartate (NMDA) and the Ca2+ ionophore A23187 stimulated NO synthase
      activity in cerebellar granule cells but not in astrocytes. In granule cells,
      NMDA, A23187, and sodium nitroprusside (SNP) elicited an accumulation of cGMP,
      whereas only SNP was active in astrocytes. However, in astrocytes that were
      incubated together with granule cells, NMDA induced a more than 3-fold increase
      in the concentration of cGMP; this increase was blocked by both the NO synthase
      inhibitor NG-monomethyl-L-arginine (MeArg) and the allosteric NMDA receptor
      antagonist (+)5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate (MK
      801). Thus, cerebellar astrocytes do not appear to express NO synthase but do
      contain guanylate cyclase, which can be activated by an NO-like factor produced
      by cerebellar granule cells after stimulation by NMDA.

PMID- 1371860
TI  - The organisation of fibres within the rat basis pedunculi.
AB  - The organisation of corticofugal fibres within the basis pedunculi of rats was
      studied using wheat germ agglutinin-horseradish peroxidase as an orthograde
      tracer. Following cortical injections, labelled fibres were distributed within
      the cerebral peduncle in an orderly way. Fibres which originate from cells in the
      frontal cortex maintain a position in the ventromedial part of the basis
      pedunculi. Fibres from the occipital and temporal cortex travel in the most
      dorsolateral part. Somatosensory fibres travel between these two. The extent of
      labelled fibres within the peduncles is correlated with the relative density of
      corticopontine cells arising from different areas of the cerebral cortex.

PMID- 1371861
TI  - Appearance of paired nucleated, Tau-positive glia in patients with progressive
      supranuclear palsy brain tissue.
AB  - Many Tau-positive glia with paired nuclei and astrocyte type morphology were
      identified in three brains from patients with progressive supranuclear palsy
      (PSP). They were positive by Bielschowsky's and Bodian's silver staining as well
      as by immunostaining with Tau-2, Alz-50, anti-GFAP and anti-paired helical
      filament antibodies, but not with anti-ubiquitin antibody. They were
      predominantly localized in the striatum, thalamus and frontal cortex but were not
      seen in white matter and were not plentiful in areas of heavy neuronal
      degeneration. Electron microscopy clearly showed the nuclear pairing and
      localized the Tau protein to bundles suggestive of microtubules in the cytoplasm
      and proximal processes. Such glial cells were rarely seen in cases of other
      neurodegenerative diseases or neurologically normal controls. These data suggest
      that there is an unusual gliotic reaction in PSP in brain areas which show
      relatively little neuronal loss.

PMID- 1371862
TI  - [Quantitative morpho- and densitometric parameters in the evaluation of
      aspiration cytology smears of the breast].
AB  - Quantitative morpho- and densitometric analysis of Feulgen stained breast
      aspiration smears were performed by absorption cytophotometer and a TV image
      analyser. The DNA Index, and the ratio of G1-S-G2 phase fraction ratio yielded by
      the quantitative DNA analysis, showed significant differences between benign and
      malignant alterations. Based on the 13 morphometric and 5 densitometric
      parameters the TV-image analyser could classify the examined smears 80% correctly
      by cluster analysis. Groups of the cytological Grade I.-III. were also
      differentiable by this method. The application of TV image analyser system in the
      diagnosis of aspiration cytological smears could be suggested. The complex
      quantitative morpho- and densitometric analysis could contribute to the correct
      classification of diploid tumours.

PMID- 1371863
TI  - Genomic organisation and expression of a differentially-regulated gene family
      from Leishmania major.
AB  - We have isolated and characterised a differentially-regulated gene family in the
      protozoan parasite Leishmania major. The family contains 5 genes linked within a
      10Kb region of the genome: three of the genes are closely related in DNA
      sequence, the other two have only limited homology. Post-transcriptional control
      of the differential expression pattern is suggested by detection of precursor RNA
      molecules containing intergenic sequences and evidence that mature mRNA molecules
      contain a 35nt spliced leader sequence at their 5' ends. These features support a
      model of polycistronic transcription in which the stability and differential
      processing of precursor RNA molecules determine the steady state levels of mature
      mRNA. We have identified several DNA sequence motifs within the gene family that
      have potential roles in differential processing and/or RNA stability: an
      alternative 5' splice acceptor site for trans-splicing; a putative
      polyadenylation site; and a region of potential secondary structure within 3'
      flanking sequences. The 3' sequence elements are conserved in those genes that
      share the same pattern of differential regulation. To our knowledge, this is the
      first example of coordinated differential-regulation of a non-identical gene
      cluster in Leishmania.

PMID- 1371864
TI  - Increased specificity for antisense oligodeoxynucleotide targeting of RNA
      cleavage by RNase H using chimeric methylphosphonodiester/phosphodiester
      structures.
AB  - One of the inherent problems in the use of antisense oligodeoxynucleotides to
      ablate gene expression in cell cultures is that the stringency of hybridization
      in vivo is not subject to control and may be sub-optimal. Consequently,
      phosphodiester or phosphorothioate antisense effectors and non-targeted cellular
      RNA may form partial hybrids which are substrates for RNase H. Such processes
      could promote the sequence dependent inappropriate effects recently reported in
      the literature. We have attempted to resolve this problem by using chimeric
      methylphosphonodiester/phosphodiester oligodeoxynucleotides. In contrast to the
      extensive RNA degradation observed with all-phosphodiester oligodeoxynucleotides,
      highly modified chimeric antisense effectors displayed negligible, or
      undetectable, cleavage at non-target sites without significantly impaired
      activity at the target site. We also note that all of the all-phosphodiester
      oligodeoxynucleotides tested demonstrated inappropriate effects, and that such
      undesirable activity could vary widely between different sequences.

PMID- 1371865
TI  - Formation of phosphonester bonds catalyzed by DNA polymerase.
AB  - 3'-Fluoro-2',3'-dideoxythymidine 5'-(alpha-methylphosphonyl)-beta,gamma-
      diphosphate and 2'-deoxythymidine-5'-(alpha-methylphosphonyl)-beta, gamma-
      diphosphate have been synthesized. Both compounds are incorporated into DNA
      chains during catalysis by reverse transcriptases of human immunodeficiency (HIV)
      and avian myeloblastosis (AMV) viruses, DNA polymerase beta from rat liver,
      terminal deoxynucleotidyl transferase from calf thymus and (at a very low rate)
      is by E. coli DNA polymerase I, Klenow fragment. The first compound is a
      termination substrate while the second is capable of multiple incorporation into
      the DNA chains. For instance, reverse transcriptase catalysis resulted in the
      appearance of 8 residues of second compound. DNA polymerases alpha and epsilon
      from human placenta incorporated none of the above compounds into DNA chains,
      although an inhibition of DNA synthesis by both compounds was observed with all
      enzymes mentioned. The 3'----5'-exonuclease activity of DNA polymerase I, Klenow
      fragment, hydrolyzed DNA fragments containing phosphonomethyl internucleoside
      groups, while such DNA fragments were resistant to the E. coli exonuclease III.

PMID- 1371866
TI  - Thermodynamic parameters for loop formation in RNA and DNA hairpin tetraloops.
AB  - We determined the melting temperatures (Tm) and thermodynamic parameters of 15
      RNA and 19 DNA hairpins at 1 M NaCl, 0.01 M sodium phosphate, 0.1 mM EDTA, at pH
      7. All these hairpins have loops of four bases, the most common loop size in 16S
      and 23S ribosomal RNAs. The RNA hairpins varied in loop sequence, loop-closing
      base pair (A.U, C.G, or G.C), base sequence of the stem, and stem size (four or
      five base pairs). The DNA hairpins varied in loop sequence, loop-closing base
      pair (C.G, or G.C), and base sequence of the four base-pair stem. Thermodynamic
      properties of a hairpin may be represented by nearest-neighbor interactions of
      the stem plus contributions from the loop. Thus, we obtained thermodynamic
      parameters for the formation of RNA and DNA tetraloops. For the tetraloops we
      studied, a free energy of loop formation (at 37 degrees C) of about +3 kcal/mol
      is most common for either RNA or DNA. There are extra stable loops with delta G
      degrees 37 near +1 kcal/mol, but the sequences are not necessarily the same for
      RNA and DNA. The closing base pair is also important; changing from C.G to G.C
      lowered the stability of several tetraloops in both RNA and DNA. These values
      will be useful in predicting RNA and DNA secondary structures.

PMID- 1371867
TI  - Processing in the 5' region of the pnp transcript facilitates the site-specific
      endonucleolytic cleavages of mRNA.
AB  - The primary transcript of pnp, the gene encoding polynucleotide phosphorylase in
      Escherichia coli, is processed in the 5' end region by ribonuclease III (RNase
      III). The unprocessed transcript shows enhanced stability compared with the
      processed transcript. We report here that, unlike the processed transcript, the
      unprocessed pnp transcript did not accept endonucleolytic attack at, at least,
      five cleavage sites. Sequencing analysis of the four cleavage products shows no
      sequence specific to all these sites, but AU rich stretches were observed at
      three sites.

PMID- 1371868
TI  - The primary transcription unit of the human alpha 2 globin gene defined by
      quantitative RT/PCR.
AB  - We have set up an experimental system to map the primary transcription unit of
      the human alpha 2 globin gene. The duplicated human alpha globin genes (alpha 2
      alpha 1) were linked to the alpha globin locus Positive Regulatory Element (PRE)
      and stably transfected into murine erythroleukaemia cells. We then developed a
      quantitative reverse transcriptase, polymerase chain reaction assay to map alpha
      2 primary transcripts using primer pairs derived from different parts of the
      alpha 2 globin gene and its 3' flanking region. This approach has revealed the
      presence of steady state nuclear RNA past the poly(A) site of the alpha 2 globin
      gene at approximately 40% of the level of unspliced intron transcript.
      Furthermore, these 3' flanking transcripts diminish 500 bp into the 3' flanking
      region, identifying this part of the alpha 2 globin gene as the principal region
      of termination of transcription.

PMID- 1371869
TI  - Screening for mutations by RNA single-strand conformation polymorphism (rSSCP):
      comparison with DNA-SSCP.
AB  - Single-strand conformation polymorphism (SSCP) is a simple method for detecting
      the presence of mutations in a segment of DNA, but the fraction of all mutations
      detected is unclear. We have evaluated SSCP for the detection of single-base
      mutations in the factor IX gene. Multiple conditions were examined including
      electrophoresis temperature, electrophoresis buffer concentration, acrylamide to
      bis-acrylamide ratio, and water-cooled versus fan-cooled gel apparatuses.
      Depending on conditions, 10-11 of 12 known mutations were detected in a 183 bp
      segment whereas only 11-14 of 22 known mutations were detected in a 307 bp
      segment. We hypothesized that single stranded RNA should have a larger repertoire
      of secondary structure because shorter hairpins form stable duplexes and the 2'
      hydroxyl group is available for sugar-base and sugar-sugar hydrogen bonds. By
      incorporating phage promoter sequences into PCR primers, RNA-SSCP (rSSCP) could
      be compared directly with standard DNA SSCP. rSSCP was generally superior to
      SSCP, especially for the 307 bp segment. In addition, the abundance of transcript
      produced as a result of rSSCP allows the rapid, nonradioactive detection of
      mutations by staining the gel with ethidium bromide. To gauge the utility of the
      method in a prospective manner, a blinded study was performed in which SSCP,
      rSSCP, and direct genomic sequencing were compared in 28 patients with hemophilia
      B. A total of 2.6 kb of factor IX genomic sequence was examined in nine regions
      ranging from 180 to 497 nucleotides of factor IX sequence. Sequence changes at 20
      different sites were detected by direct genomic sequencing; 70% of these were
      detected by rSSCP while only 35% were detected by SSCP.

PMID- 1371870
TI  - In vitro chromatin assembly promoted by the Xenopus laevis S-150 cell-free
      extract is enhanced by treatment with RNase A.
AB  - Cell-free extracts employed as chromatin assembly systems contain a myriad of
      proteins, polyanions and nucleic acids. The roles of ATP, MgCl2 and other
      cofactors in the catalysis of nucleosome formation by the Xenopus laevis oocyte S
      150 have yet to be established unequivocally. In this study we examine the
      influence of RNA in the assembly process. Under reaction conditions that inhibit
      nucleosome formation (+ EDTA), pretreatment of the extract with RNase A revives
      the chromatin assembly machinery while the rate of DNA supercoiling is stimulated
      significantly. Addition of purified RNA blocks DNA supercoiling. Taken together,
      these data suggest that the parameters surrounding in vitro chromatin assembly
      are variable and subject to modulation by endogenous factors.

PMID- 1371871
TI  - Sequence of the ribonuclease P RNA gene from the cyanobacterium Anacystis
      nidulans.

PMID- 1371872
TI  - Cytokeratin immunoreactivity in malignant fibrous histiocytoma and spindle cell
      tumors: comparison between frozen and paraffin-embedded tissues.
AB  - Cytokeratin (CK) immunoreactivity in malignant fibrous histiocytoma (MFH) and
      other selected cases of spindle cell tumors were assessed using two cytokeratin
      monoclonal antibodies, AE1/AE3 and CAM 5.2. Frozen tissue was used to minimize
      the effects of fixation on keratin antigenicity; in addition, one block of fixed,
      paraffin-embedded tissue was tested for comparison. CK immunoreactivity was noted
      in nine frozen tissue samples (7/20 [35%] MFH, 1/3 schwannomas, 1/3
      leiomyosarcomas). In the majority of cases, only rare individual positive cells
      were seen. Of 19 MFH cases in paraffin-embedded tissue, CK immunoreactivity was
      noted in three (16%). All 32 cases examined showed vimentin immunoreactivity. MFH
      must be added to the growing list of mesenchymal tumors exhibiting sporadic CK
      immunoreactivity. Such reactivity is less frequent in paraffin-embedded tissues.
      This finding has important implications for tumor diagnosis, particularly in the
      differential diagnosis of pseudosarcomatous carcinoma. Caution is recommended in
      the interpretation of CK immunoreactivity, particularly as it relates to
      speculations regarding histogenesis.

PMID- 1371873
TI  - Peripheral neuroepithelioma: a light microscopic, immunocytochemical, and
      ultrastructural study.
AB  - Forty-two cases of peripheral neuroepithelioma (PN) retrieved from the files of
      the National Cancer Institute (Bethesda, MD) and the Pathology Department of
      Padua University, Italy, were reviewed. No sex predilection was observed
      (25M/17F) and ages ranged from 7 to 54 yr (median 22 yr). Roughly a third of the
      tumors were thoracopulmonary ("Askin tumor"), a third were axial, and a third
      were in extremities. A lobular pattern with rosettes or pseudo-rosettes
      characterized PN. Seventeen cases showed a strong diastase-sensitive PAS
      positivity. Transitional areas with an Ewing's-like appearance and, in one case,
      transition to malignant nerve sheath tumor have been documented. The presence of
      neuron specific enolase (NSE), S-100 protein, HNK-1, neurofilaments, vimentin,
      keratin (AE1-AE3), beta 2-microglobulin, chromogranin A, and synaptophysin was
      investigated using the avidin-biotin technique. Immunocytochemically, NSE (95% of
      cases), beta 2-microglobulin (77.5%), synaptophysin (73.3%), and S-100 protein
      (67.5%) were the most consistently positive markers. Ultrastructurally, PN is
      characterized by a primitive appearance, although it was routinely possible to
      recognize neural features such as primitive neuritic extensions and dense core
      granules, either in the cytoplasm or in the cellular processes. In our
      experience, a light microscopic picture of a primitive round cell tumor with a
      lobular pattern, and particularly with rosettes when present, with NSE and beta 2
      microglobulin positivity by immunocytochemistry, ideally with positive
      synaptophysin, along with supportive electron microscopy, is required for the
      diagnosis of PN. Conversely, no one feature alone is generally sufficient for
      diagnosis, but does allow distinction from extraosseous Ewing's, which (like
      osseous Ewing's) lacks features of neural differentiation.

PMID- 1371874
TI  - Estrogen and progesterone receptor detection in archival formalin-fixed, paraffin
      embedded tissue from breast carcinoma: a comparison of immunohistochemistry with
      the dextran-coated charcoal assay.
AB  - The steroid receptor (estrogen (ER) and progesterone receptor (PR] status was
      studied in 94 cases of invasive breast carcinoma from three separate
      institutions. All cases had fresh tissue examined for ER and PR by the dextran
      coated charcoal cytosolic assay (DCC), and each case was examined
      immunohistochemically for ER and PR from archival formalin-fixed, paraffin
      embedded tissue. Immunohistochemical assays (IH) were reviewed blinded to the DCC
      results and scored in a semiquantitative fashion prior to comparison to the DCC
      results. Overall, there was agreement between DCC and IH in 89% of ER and in 87%
      of PR assays. Some 50% of the ER discorrelations were of the IH-positive DCC
      negative type, while 27% of the PR discorrelations were of this type. In four
      cases, both ER and PR did not correlate between IH and DCC determinations, with
      two being IH (ER and PR) positive and DCC negative, and two of the opposite type.
      The results of the study show that steroid receptor assays performed on routinely
      processed formalin-fixed archival material are reliable and closely recapitulate
      the results of traditional biochemical assays. Results suggest that, in the cases
      where IH is positive while DCC is negative, the IH result may actually provide a
      more reliable receptor status of the tumor than does the DCC result.
      Semiquantitation of fixed tissue IH assays shows a trend toward quantitative
      correlation with DCC results, but this correlation is weak, and factors
      concerning fixation and processing are most likely to be responsible.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1371875
TI  - Complete folding of bovine pancreatic trypsin inhibitor with only a single
      disulfide bond.
AB  - In the oxidative folding of bovine pancreatic trypsin inhibitor (BPTI) at neutral
      pH, only two one-disulfide intermediates accumulate to a significant extent,
      namely [5-55] and [30-51]. In this paper we describe a recombinant model of [5
      55], designated [5-55]Ala, which was made by replacing the cysteine residues not
      involved in the disulfide bond with alanine. As judged by two-dimensional NMR, [5
      55]Ala folds into essentially the same conformation as native BPTI. Moreover,
      like native BPTI, [5-55]Ala inhibits trypsin stoichiometrically. Thus, the
      disulfide-bonded intermediate [5-55] corresponds not to a partially folded
      protein folding intermediate but rather to an essentially completely folded
      protein. This conclusion provides an explanation for many of the thermodynamic
      and kinetic properties of [5-55] in the folding pathway of BPTI.

PMID- 1371876
TI  - Intrinsic anion channel activity of the recombinant first nucleotide binding fold
      domain of the cystic fibrosis transmembrane regulator protein.
AB  - The first nucleotide binding fold (NBF-1) from the cystic fibrosis transmembrane
      regulator (CFTR) has been expressed in bacteria and found to bind ATP and to
      express anion channel activity when reconstituted onto a planar lipid bilayer.
      This evidence suggests that the NBF forms the anion-selective portion of the CFTR
      channel. We also found that the recombinant NBF-1 anion channel is blocked by ATP
      (1 mM), under which condition it appears to have a minimal conductance of
      approximately 9 pS and an ohmic current-voltage relationship. We further found
      that the recombinant NBF-1 bearing the delta F508 mutation has nearly identical
      anion channel activity to that of the wild-type protein but can be distinguished
      from wild type under bianionic conditions with chloride and gluconate. We
      conclude from these data that the anion channel activity of the recombinant NBF-1
      could represent all or part of the anion conductance mechanism of CFTR and that
      the role of the ATP binding by the NBF could be to modulate this anion channel
      activity.

PMID- 1371877
TI  - Role of the alpha v beta 3 integrin in human melanoma cell invasion.
AB  - The human melanoma cell line A375M expresses the vitronectin receptor (alpha v
      beta 3 integrin) on its cell surface. Treatment of A375M cells with either
      polyclonal or monoclonal anti-alpha v beta 3 antibodies resulted in stimulation
      of invasion through basement membrane matrices in vitro. Similar treatment of
      these cells with a monoclonal anti-alpha v antibody, which does not inhibit the
      adhesive function of the alpha v beta 3 antigen, also stimulated invasion;
      however, anti-beta 3 antibody treatment had no effect. Furthermore, pretreatment
      of the cells with vitronectin or addition of vitronectin to the basement membrane
      matrix also resulted in stimulation of invasion. Similar treatments with
      fibronectin receptor antibody or fibronectin had no effect on invasion. Analysis
      of type IV collagenase expression in cells treated with anti-alpha v beta 3
      antibody showed higher levels of both the secreted 72-kDa enzyme and its mRNA.
      Signal transduction through the alpha v beta 3 integrin could underlie the
      elevated expression of metalloproteinase and the enhanced invasion of A375M cells
      through basement membrane matrices.

PMID- 1371878
TI  - Primary cultures of endothelial cells from the human liver sinusoid are
      permissive for human immunodeficiency virus type 1.
AB  - Human endothelial cells isolated from hepatic sinusoids were infected in vitro
      with human immunodeficiency virus type 1 (HIV-1). An early sign of infection
      occurring in the culture was the formation of multinucleated cells. By double
      labeling immunofluorescence, 5-15% of the cells recognized as endothelial cells
      owing to the presence of von Willebrand factor were found to contain HIV p24 and
      gp120 antigens after 2 weeks. Reverse transcriptase activity was released into
      the medium, and different steps in the process of viral budding were observed by
      electron microscopy. The virus produced by the endothelial cells was found to be
      infectious for CEM cells, a human T-cell line. CD4 molecules are present at the
      surface of the endothelial cells, as demonstrated by immunogold-silver staining
      and backscattered electron imaging. Treatment with an anti-CD4 antibody abolished
      productive infection of the sinusoidal endothelial cells. The possibility that
      endothelial cells of the liver sinusoid are infected in vivo with HIV remains to
      be clearly shown.

PMID- 1371880
TI  - Regulation of Cl- channels in normal and cystic fibrosis airway epithelial cells
      by extracellular ATP.
AB  - The rate of Cl- secretion by human airway epithelium is determined, in part, by
      apical cell membrane Cl- conductance. In cystic fibrosis airway epithelia,
      defective regulation of Cl- conductance decreases the capability to secrete Cl-.
      Here we report that extracytosolic ATP in the luminal bath of cultured human
      airway epithelia increased transepithelial Cl- secretion and apical membrane Cl-
      permeability. Single-channel studies in excised membrane patches revealed that
      ATP increased the open probability of outward rectifying Cl- channels. The latter
      effect occurs through a receptor mechanism that requires no identified soluble
      second messengers and is insensitive to probes of G protein function. These
      results demonstrate a mode of regulation of anion channels by binding ATP at the
      extracellular surface. Regulation of Cl- conductance by external ATP is preserved
      in cystic fibrosis airway epithelia.

PMID- 1371879
TI  - p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase
      activity but not tyrosine phosphorylation of p21ras GTPase-activating protein.
AB  - Products of the ras gene family, termed p21ras, are GTP-binding proteins that
      have been implicated in signal transduction via receptors encoding tyrosine
      kinase domains. Recent findings have defined a superfamily of hemopoietin
      receptors that includes receptors for a number of interleukins and colony
      stimulating factors. The intracellular portions of these receptors show only
      restricted homologies, have no tyrosine kinase domain, and provide no clues to
      the mode of signal transduction. However, in most cases the factors stimulate
      tyrosine phosphorylation. We demonstrate here that ligand-induced activation of
      the interleukin (IL)-2, IL-3, IL-5, and granulocyte-macrophage colony-stimulating
      factor receptors resulted in activation of p21ras in various hemopoietic cell
      lines. The only cytokine tested that binds to a hemopoietin receptor and that did
      not activate p21ras was IL-4. Activation of p21ras was also observed in response
      to Steel factor, which stimulates the endogenous tyrosine kinase activity of the
      c-kit receptor, as well as with phorbol esters, which activate protein kinase C.
      Experiments with protein kinase inhibitors implicated tyrosine kinase activity,
      but not protein kinase C activity, as the upstream signal in p21ras activation
      via these growth factor receptors. Attempts to demonstrate tyrosine
      phosphorylation of the p21ras GTPase-activating protein (GAP) were negative,
      suggesting that phosphorylation of GAP may not be the major mechanism for
      regulation of p21ras activity by tyrosine kinases.

PMID- 1371881
TI  - A synthetic peptide of the rab3a effector domain stimulates amylase release from
      permeabilized pancreatic acini.
AB  - In this study we have employed a synthetic peptide of the rab3a effector domain,
      rab3AL, to examine whether a rab-like low molecular weight GTP-binding protein is
      involved in protein release from the rat pancreatic acinar cell. The peptide was
      found to be a potent stimulator of amylase release from streptolysin-O
      permeabilized pancreatic acini, with an EC50 of approximately 60 microM.
      Stimulation of amylase discharge by rab3AL did not occur using either intact
      acini or permeabilized acini depleted of ATP. In contrast, a different effector
      domain peptide of the rab2 protein, rab2AL, a peptide with distinct sequence
      homology to rab3AL, was unable to stimulate amylase release, suggesting the
      specificity of the rab3AL response to rab3-like proteins. rab3AL stimulated
      release at [Ca2+] that were nonstimulatory in the absence of the peptide (10 nM).
      rab3AL potentiated the effect of guanosine 5'-[gamma-thio]triphosphate on amylase
      secretion and decreased the amount of guanosine 5'-[gamma-thio]triphosphate
      required for maximal secretion, suggesting that these two agents interact to
      modulate a distal step(s) of secretion. The above results provide functional
      evidence for the role of a rab-like low molecular weight GTP-binding protein and
      its effector protein(s) in the control of protein release from pancreatic acini.
      Because the discharge response to rab3AL is near the maximal obtainable from
      permeabilized acini, our results would suggest that rab3-like proteins control an
      important step in regulated secretion of amylase.

PMID- 1371882
TI  - Role of the KIT protooncogene in normal and malignant human hematopoiesis.
AB  - The role of the KIT protooncogene in human hematopoiesis is uncertain. Therefore,
      we examined KIT mRNA expression in normal human bone marrow mononuclear cells
      (MNC) and used antisense oligodeoxynucleotides (oligomers) to disrupt KIT
      function. KIT mRNA was detected with certainty only in growth factor-stimulated
      MNC. Expression was essentially abrogated by making MNC quiescent or by
      inhibiting myb gene function. Oligomers blocked KIT mRNA expression in a dose
      response and sequence-specific manner, thereby allowing functional examination of
      the KIT receptor. In experiments with either partially purified or CD34(+)
      enriched MNC, neither granulocyte nor megakaryocyte colony formation was
      inhibited by oligomer exposure. In contrast, KIT antisense oligomers inhibited
      interleukin 3/erythropoietin-driven erythroid colony formation approximately 70%
      and "stem cell factor"/erythropoietin-driven colony formation 100%. The presence
      of erythroid progenitor cell subsets with differential requirements for KIT
      function is therefore suggested. Growth of hematopoietic colonies from chronic
      myeloid leukemia and polycythemia vera patients was also inhibited, while acute
      leukemia colony growth appeared less sensitive to KIT deprivation. These results
      suggest that KIT plays a predominant role in normal erythropoiesis but may be
      important in regulating some types of malignant hematopoietic cell growth as
      well. They also suggest that KIT expression is linked to cell metabolic activity
      and that its expression may be regulated by or coregulated with MYB.

PMID- 1371884
TI  - Interleukin 10 is a potent growth and differentiation factor for activated human
      B lymphocytes.
AB  - Interleukin 10 (IL-10), originally identified as a TH2 helper T-cell product able
      to inhibit cytokine production by TH1 cells, is highly homologous to BCRF1 (viral
      IL-10), an open reading frame in the Epstein-Barr virus genome. Here, we show
      that human and viral IL-10 stimulate DNA replication of B lymphocytes activated
      either via their antigen receptor or via their CD40 antigen. IL-4 and IL-10
      display additive effects and induce a strong increase in the number of viable
      cells. Moreover, IL-10 induces activated B cells to secrete large amounts of IgG,
      IgA, and IgM, and the combination of IL-10 and IL-4 results in the secretion of
      the four immunoglobulin isotypes. Thus, IL-10 may play an important role in the
      amplification of humoral responses.

PMID- 1371883
TI  - Modulation of dihydropyridine-sensitive calcium channels in heart cells by fish
      oil fatty acids.
AB  - The highly unsaturated n-3 fatty acids from fish oils, eicosapentaenoic acid
      [EPA; C20:5 (n-3)] and docosahexanoic acid [DHA; C22:6 (n-3)], prevent the
      toxicity of high concentrations of the cardiac glycoside ouabain to isolated
      neonatal rat cardiac myocytes. Arachidonic acid [C20:4 (n-6)] lacks such
      protective action. The protective effect of the n-3 fatty acids is associated
      with their ability to prevent high levels of cytosolic free calcium from
      occurring in response to the ouabain. This in turn results, at least in part,
      from a 30% reduction in calcium influx rate induced by the n-3 fatty acids. This
      protective effect is simulated by nitrendipine, a dihydropyridine inhibitor of
      the L-type calcium channels in cardiac myocytes. Nitrendipine (0.1 mM) alone,
      however, inhibits myocyte contractility, as do verapamil (10 microM) and
      diltiazem (1.0 microM). EPA or DHA (5 microM) blocks the inhibitory effects of
      nitrendipine but not those of verapamil or diltiazem. Bay K8644, a known
      dihydropyridine agonist of L-type calcium channels, produces a ouabain-like
      effect that is also prevented by EPA or DHA. Specific binding of [3H]nitrendipine
      to intact myocytes is noncompetitively inhibited by EPA or DHA in a manner that
      reduces the number of high- and low-affinity binding sites (Bmax) and increases
      their affinities. The fish oil fatty acids prevent calcium overload from ouabain
      and Bay K8644. They also prevent a calcium-depleted state in the myocytes caused
      by the L-type calcium channel blocker nitrendipine. The protective effects of the
      n-3 fatty acids appear to result from their modulatory effects on nitrendipine
      sensitive L-type calcium channels.

PMID- 1371885
TI  - Insulin-like growth factor I gene expression is induced in astrocytes during
      experimental demyelination.
AB  - To investigate insulin-like growth factor I (IGF-I) and IGF-I receptor gene
      expression during experimental demyelination and myelin regeneration, young mice
      were fed cuprizone (( bis(cyclohexanone) oxaldihydrazone )). This copper
      chelating agent produces demyelination in the corpus callosum and superior
      cerebellar peduncles, and when treatment is stopped, there is rapid
      remyelination. At intervals during cuprizone treatment and recovery, brain
      sections were hybridized with specific probes and immunostained with antibodies
      to determine the localization and relative amounts of IGF-I and IGF-I receptor
      mRNAs and peptides. In untreated littermates, IGF-I and IGF-I receptor mRNAs and
      peptides were not detected in white matter. In cuprizone-treated mice, high
      levels of both IGF-I mRNA and peptide were expressed by astrocytes in areas of
      myelin breakdown. Astrocyte IGF-I expression decreased rapidly during recovery
      and oligodendroglial expression of myelin-related genes increased. In severely
      demyelinated areas, immature oligodendroglia exhibited a transient increase in
      IGF-I receptor mRNA and peptide immunoreactivity during early recovery. This
      highly specific pattern of IGF-I induction in astrocytes during demyelination and
      the expression of the IGF-I receptor in regenerating oligodendrocytes during
      recovery suggest that IGF-I functions in the regulation of oligodendrocyte and
      myelin metabolism in vivo.

PMID- 1371886
TI  - Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase
      contributes to the development of high-level resistance to zidovudine.
AB  - It is recognized that high-level resistance to 3'-azido-3'-deoxythymidine (AZT,
      zidovudine, or Retrovir) is conferred by the presence of four mutations in the
      human immunodeficiency virus (HIV) reverse transcriptase [RT; deoxynucleoside
      triphosphate:DNA deoxynucleotidyltransferase (RNA-directed), EC 2.7.7.49] coding
      sequence. However, a number of clinical isolates have been observed that exhibit
      high-level resistance but contain only three of the four identified mutations
      (Asn-67, Arg-70, and Tyr-215). Construction of a molecular clone with this
      genotype gave rise to only a partially resistant virus, raising the possibility
      that an additional mutation existed in some clinical isolates. Using an HIV
      marker rescue system, we have mapped and identified a fifth mutation conferring
      resistance to zidovudine, namely, methionine to leucine at codon 41 of HIV RT. An
      infectious molecular clone containing this mutation together with three
      previously identified mutations in the RT coding sequence yielded highly
      resistant HIV after transfection of T cells. Direct detection of the fifth
      mutation in DNA samples from cocultured peripheral blood lymphocytes by the PCR
      revealed that it occurred relatively early in the development of zidovudine
      resistance. However, this mutation was only detected after the appearance of the
      codon 215 change in the RT coding sequence. Identification of this mutation in
      addition to the other known mutations conferring resistance enables rapid and
      direct correlation between an RT genotype and sensitivity of the virus.

PMID- 1371887
TI  - Hoechst 33258 photosensitization of 5-iododeoxyuridine-substituted DNA to 365 nm
      light: dependence of dehalogenation on the dye-to-nucleotide ratio.
AB  - DNA containing 5-iododeoxyuridine substituted at levels ranging from 1 to 24% was
      irradiated at 365 nm in the presence of various amounts of the Hoechst dye 33258.
      The subsequent loss of iodine was measured by following the loss of radioactive
      iodine (125I) from filter immobilized DNA subjected to repeated washings. A plot
      of the photochemical cross section (sigma B) for this process as a function of r,
      the molar ratio of dye added per nucleotide present, shows a maximum at r = 0.04
      to 0.06, followed by a decrease with increasing dye-to-phosphate ratios to give a
      minimum at r = 0.5. Increasing the amounts of dye further results in sigma B
      reaching a second maximum at r greater than or equal to 1, after which it levels
      off. An attempt was made to interpret these results in terms of the binding
      models currently employed for analyzing binding of Hoechst dye to DNA. Chain
      breaks as measured in alkali were also measured and found to be enhanced by the
      dye; the ratio of breaks per iodine loss was 0.9.

PMID- 1371888
TI  - Inhibitory effect of prostaglandin delta 12-PGJ2 on cell proliferation and alpha
      fetoprotein expression in HuH-7 human hepatoma cells.
AB  - 9-deoxy-delta 9,delta 12-13,14-dihydro-prostaglandin D2 (delta 12-PGJ2) is a
      potent inhibitor of proliferation of tumor cells. In the present study, the
      effect of delta 12-PGJ2 on the alpha-fetoprotein(AFP) and the albumin gene
      expression was analyzed in HuH-7 human hepatoma cells. delta 12-PGJ2 inhibited
      the cell growth and reduced the medium AFP concentrations dose-dependently. To
      determine whether this decline of AFP depends only on the relative decrease in
      cell numbers by delta 12-PGJ2, or is in part, due to the decrease in the cellular
      AFP synthesis by delta 12-PGJ2, Northern blot analysis was performed in this
      study. By Northern blotting, it was shown that delta 12-PGJ2 caused a marked
      reduction in the levels of the AFP mRNA and the albumin mRNA. In contrast, the
      level of the beta-actin mRNA was not changed by delta 12-PGJ2. In the transient
      chloramphnicol acetyltransferase plasmid transfection experiments, delta 12-PGJ2
      did not suppress the AFP enhancer activity, which possibly regulates both the AFP
      and the albumin gene expression in HuH-7 hepatoma cells, but resulted in the
      selective repression of the AFP and the albumin promoter activity. These results
      suggest that delta 12-PGJ2 suppresses not only cell growth but also expression of
      the AFP gene and the albumin gene at the transcriptional level in human hepatoma
      cells.

PMID- 1371889
TI  - [The value of biopsy of the accessory labial salivary glands for the diagnosis of
      amylosis].
AB  - Diagnosis of amyloidosis depends on the demonstration of amyloid deposits in
      biopsies using specific stains. Recently, in addition to classical biopsies
      (kidney, liver, gum, skin, rectal mucosa), labial salivary gland biopsy has been
      recommended as safe diagnostic method. In our recruitment, it allowed the
      fortuitous discovery of amyloidosis in three patients suffering from rheumatoid
      polyarthritis or spondylarthritis. In five other patients (2 cases of familial
      amyloidosis, 1 dysglobulinemia, 2 primary cardiac amyloidosis), biopsy was
      performed for systematic search of amyloidosis. In five of these eight cases, a
      sicca syndrome was associated with the salivary deposits. These deposits were
      stained with congo red viewed in polarized light and with T thioflavine. Besides,
      Wright's method allowed to know the AL or AA type of amyloidosis and thus to
      guide the treatment. On the whole, labial salivary gland biopsy is a highly
      sensitive method for diagnosis of primary and secondary amyloidosis.

PMID- 1371890
TI  - Formation of ion-permeable channels by tumor necrosis factor-alpha.
AB  - Tumor necrosis factor-alpha (TNF, cachectin), a protein secreted by activated
      macrophages, participates in inflammatory responses and in infectious and
      neoplastic disease states. The mechanisms by which TNF exerts cytotoxic,
      hormonal, and other specific effects are obscure. Structural studies of the TNF
      trimer have revealed a central pore-like region. Although several amino acid side
      chains appear to preclude an open channel, the ability of TNF to insert into
      lipid vesicles raised the possibility that opening might occur in a bilayer
      milieu. Acidification of TNF promoted conformational changes concordant with
      increased surface hydrophobicity and membrane insertion. Furthermore, TNF formed
      pH-dependent, voltage-dependent, ion-permeable channels in planar lipid bilayer
      membranes and increased the sodium permeability of human U937 histiocytic
      lymphoma cells. Thus, some of the physiological effects of TNF may be elicited
      through its intrinsic ion channel-forming activity.

PMID- 1371892
TI  - Using metaphors in therapy: dichos and Latino clients.
AB  - The clinical literature has given increased attention to the importance of
      culturally appropriate interventions with diverse populations. The use of
      metaphor as a tool in psychotherapy has become increasingly salient. Metaphor can
      also be used in work with Latino clients through the incorporation of dichos, or
      sayings, that exist in Mexican American and other Latino cultures. These folk
      sayings exhibit cultural beliefs and ideals embedded in figurative language that
      describe the human condition. The Spanish language has crystallized human
      situations, frailties, and anecdotes in the dichos used in everyday
      conversations. These dichos offer the clinician culturally viable tools for
      mitigating resistance, enhancing motivation, or reframing problems. Importantly,
      dichos provide an ambience that contributes to culturally sensitive treatment.

PMID- 1371891
TI  - Inhibition of development of Kaposi's sarcoma-related lesions by a bacterial cell
      wall complex.
AB  - In vitro and in vivo model systems for the study of human immunodeficiency virus
      (HIV)-associated Kaposi's sarcoma (KS) were used to evaluate compounds for their
      potential as therapeutic agents. A sulfated polysaccharide-peptidoglycan compound
      (SP-PG) produced by bacteria controlled the in vitro growth of acquired
      immunodeficiency syndrome (AIDS)-associated, KS-derived spindle-shaped cells
      (AIDS-KS cells) at noncytotoxic concentrations. Angiogenesis induced by AIDS-KS
      cells in the chicken chorioallantoic membrane assay was blocked by SP-PG, which
      also inhibited the vascular hyperpermeability response and the angiogenesis
      associated with the induction of KS-like lesions that develop after subcutaneous
      inoculation of AIDS-KS cells into nude mice. Suramin, pentosan polysulfate, and
      interferon alpha, which are currently in use for therapy of KS, were either less
      effective than SP-PG or much more cytotoxic, or both.

PMID- 1371893
TI  - Optimal palliation of pancreatic carcinoma.

PMID- 1371894
TI  - Evaluation of heat sterilization of commercial rat diets for use in FDA
      toxicological studies.
AB  - Certified commercial rat diets, control and fortified, in the form of pellets and
      meal, were evaluated in a simulated subchronic rat feeding study. The diets were
      analyzed before and after autoclaving to determine nutrient integrity and loss,
      as well as the efficiency of autoclaving for removal of microbiological
      contaminants. Sterilization reduced the level of heat-labile vitamins, but
      protein level was minimally reduced. Sterilization eliminated most of the
      bacterial contaminants and virtually all the mold and yeast colonies. Male and
      female Osborne-Mendel rats (3-4 wk old) were fed control or sterilized diet for 6
      wk. Both males and females consumed more pelleted chow than meal chow. This
      apparent difference in consumption may be due to wastage of pellets, because
      there were no differences in male or female growth during the 6-wk study. At
      necropsy, no gross pathology was noted, and organ weights did not differ
      significantly among the groups for either sex. Testicular weights were also
      similar among the groups. Blood serum proteins were analyzed by electrophoresis
      to screen for possible effects on various target organs. Gamma globulin levels
      for female rats fed sterilized meal were significantly reduced compared to levels
      for rats fed the control diet. These results suggest that either nutritional
      factors or heat inactivation of the microbes affects basal levels of humoral
      immunity, possibly by reduction of gut-mediated immune responses.

PMID- 1371896
TI  - Comparison of two approved enzyme immunoassays for the detection of antibodies to
      the hepatitis C virus in 5216 United States blood donors.

PMID- 1371895
TI  - Photodynamic inactivation of retrovirus by benzoporphyrin derivative: a feline
      leukemia virus model.
AB  - The ability of a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD
      MA), and either broad-spectrum (400-1200 nm) or narrow-band (600-700 nm) red
      light to kill feline leukemia virus (FeLV) and FeLV-infected cat T cells (cell
      line 3201) was investigated in culture medium containing fetal calf serum and in
      blood from infected cats. A molecular clone of FeLV, 61E, is minimally pathogenic
      and productively infects 3201 cells while causing no change in rate of cell
      division, viability, or size. Active virus (either free or within infected cells)
      was quantified by using a limiting dilution assay that involved cocultivation of
      test samples with naive 3201 cells, after which either the polymerase chain
      reaction or a reverse transcriptase assay was used to detect the presence of
      virus. It was shown that 61E-infected T cells in culture were slightly more
      sensitive to photodynamic killing than were uninfected cells. Infected cells and
      free virus were eliminated from whole blood taken from infected cats by using 4
      micrograms per mL of BPD-MA and 40 J per cm2 of red light. These results
      correlate well with previous results with BPD-MA and vesicular stomatitis virus
      in whole human blood and suggest that this photosensitizer is a promising agent
      for the elimination of retroviruses that are either free or located within
      infected cells in blood.

PMID- 1371897
TI  - Keratin-positive reticulum cells in fine needle aspirates and touch imprints of
      hyperplastic lymph nodes. A possible pitfall in the immunocytochemical diagnosis
      of metastatic carcinoma.
AB  - Fine needle aspirates and touch imprints of 36 hyperplastic (reactive) lymph
      nodes were tested for the presence of keratin and desmin. Keratin-positive cells
      with morphologic characteristics corresponding to extrafollicular (fibroblastic)
      reticulum cells were found in 18% of the fine needle aspirates and 42% of the
      touch imprints. The number of keratin-positive reticulum cells varied from 1 to
      greater than 30 per slide. Desmin-positive cells with similar morphology were
      found in 23% of fine needle aspirates and 37% of touch imprints, and the number
      of such cells per slide ranged from 2 to greater than 70. The relatively frequent
      occurrence of keratin-positive reticulum cells in these preparations from
      hyperplastic lymph nodes should be taken into account if keratin antibodies are
      used to search for carcinoma micrometastases.

PMID- 1371898
TI  - Dramatic response of a metastatic carcinoid tumour to a combination of interferon
      and octreotide.
AB  - The combination of alpha-interferon and octreotide has rarely been tested in the
      treatment of carcinoid syndrome. We describe a patient who was moribund when
      treated with interferon alone, but enjoyed a dramatic response leading to
      disappearance of all symptoms, normalization of dU-5-HIAA, and restoration of his
      normal life-style when octreotide was initiated. Neither interferon nor
      octreotide could be withdrawn without reappearance of the symptoms, suggesting
      that the combination of alpha-interferon and octreotide may have synergistic
      effects in carcinoid syndrome.

PMID- 1371899
TI  - Refractile mycobacteria in Romanowsky-stained bone marrow smears. A comparison of
      acid-fast-stained tissue sections and Romanowsky-stained smears.
AB  - The appearance of mycobacteria was studied in Wright-stained bone marrow
      preparations of human immunodeficiency virus-infected patients and compared with
      acid-fast-stained trephine biopsy sections and culture results. Mycobacterium
      avium complex in Romanowsky-stained preparations may be seen as extracellular and
      intracellular clear or red refractile beaded rods and nonrefractile "negative
      images." Refractile mycobacteria were seen in 17 of 20 culture-positive cases.
      Acid-fast stain of the trephine biopsy demonstrated organisms in only 11 of the
      20 cases. Thus, six cases were culture positive and contained refractile rods but
      had no acid-fast organisms on the trephine biopsy. No false-positive results were
      seen with Romanowsky stain; the three false-negative results for refractility
      also were negative with acid-fast stain. Examination of Romanowsky-stained smears
      or imprints for refractile mycobacteria provides a reliable and sensitive method
      to identify mycobacteria in this population. Romanowsky-stained bone marrow
      aspirate and imprint smears should be examined for refractile bacilli when
      mycobacterial infection is suspected.

PMID- 1371900
TI  - Subtyping lymphocytes in peripheral blood by direct immunoalkaline phosphatase
      labeling and light scatter/absorption flow cytometric analysis.
AB  - Evaluation of blood cells to determine immunologic status is becoming an
      important clinical application of flow cytometric analysis. For a wider use of
      immunophenotyping technology in clinical laboratories, the authors developed a
      rapid method to detect monoclonal antibody-labeled cells using forward light
      scatter/absorption clinical flow cytometers such as the Technicon H*1 and
      Technicon H*2 differential complete blood count analyzers. Calf-intestinal
      alkaline phosphatase was conjugated to mouse monoclonal antibodies (anti-CD2,
      CD3, CD4, CD8, CD19) for direct immunoenzymatic labeling. The combination of 5
      bromo-4-chloro-3-indolyl phosphate and nitroblue-tetrazolium salt in
      diethanolamine buffer at pH 9.6 was selected as buffer/substrate to yield stable,
      insoluble, and very intense purplish-blue precipitates on the surface of the
      cells labeled with monoclonal antibody-alkaline phosphatase conjugates.
      Endogenous alkaline phosphatase in granulocytes was inhibited with levamisole.
      Early mild fixation of the white cells permitted incubation at 38 +/- 1 degrees
      C, which accelerated each step of the reaction without disrupting the cells
      throughout the procedure. The method is competitive with the direct
      immunofluorescence whole-blood method used on fluorescence flow cytometers in
      speed, sensitivity, and accuracy, as demonstrated with alkaline phosphatase
      conjugated anti-CD2, CD3, CD4, CD8, CD19 monoclonal antibodies.

PMID- 1371901
TI  - Immunohistologic demonstration of myocardial proteins with applications.
AB  - The authors used antibodies specific for creatine kinase MB isoenzyme (CK-MB) and
      myosin light chain-1 (MLC-1) for immunohistologic staining. At appropriate
      dilutions of antibody, frozen sections of human heart muscle were positive for
      both CK-MB and MLC-1, whereas sections of human skeletal muscle were negative for
      both proteins. Staining for both CK-MB and MLC-1 also was demonstrated in an
      immature teratoma. Furthermore, staining was localized to the
      rhabdomyosarcomatous elements within the teratoma; other components of the tumor
      did not stain for CK-MB or MLC-1. Biopsies of skeletal muscle revealed that
      regenerative, but not intact normal or degenerating, fibers also contained CK-MB
      and MLC-1. Immunohistologic stains for CK-MB and MLC-1 may be useful as tumor
      markers and as markers for regenerative muscle fibers.

PMID- 1371902
TI  - Steroid hormone receptors in endometrial stromal sarcomas. A biochemical and
      immunohistochemical study.
AB  - Seven cases of endometrial stromal sarcoma (five low grade and two high grade)
      were analyzed immunohistochemically for the presence of estrogen and progesterone
      receptors. In four cases (three low grade and one high grade), these results were
      compared to biochemical findings. All low-grade endometrial stromal sarcomas were
      positive for progesterone receptors using immunohistochemical techniques. These
      results correlated well with biochemical evaluation of progesterone receptors.
      The high-grade endometrial stromal sarcomas were negative for progesterone and
      estrogen receptors by both methods. The advantages of immunohistochemical
      evaluation of steroid receptors have been well established in breast and
      endometrial carcinomas. This study demonstrates the usefulness of this technique
      in endometrial stromal sarcomas.

PMID- 1371903
TI  - Somatostatin-producing neuroendocrine tumor of the ampulla (ampullary
      somatostatinoma). Evidence of prosomatostatin production.
AB  - Two cases of somatostatin-producing ampullary neuroendocrine tumors
      (somatostatinoma) are reported. The authors have characterized their
      immunoreactivity using antibodies specific for the amino- and carboxyl-terminal
      portions of prosomatostatin, the precursor of somatostatin in the normal
      synthetic pathway. Cytoplasmic staining was found using each of these two
      antibodies in the tumor cells of both ampullary somatostatinomas as well as in
      the cytoplasm of cells in the hypothalamus, crypt cells of the duodenal mucosa,
      mucosal cells of the biliary tract, D cells of the pancreatic islets, and
      parafollicular cells of fetal thyroid. These studies suggest that the synthesis
      of somatostatin in ampullary somatostatinomas occurs through the normal pathway
      from the precursor prosomatostatin.

PMID- 1371904
TI  - Immunostaining of gastric leiomyosarcoma for muscle-specific actin.

PMID- 1371905
TI  - Antiplatelet effect of iloprost.

PMID- 1371906
TI  - Surgical excision of subfoveal neovascular membranes in age-related macular
      degeneration.
AB  - We studied the results of surgical excision of ten consecutive subfoveal
      choroidal neovascular membranes in ten patients with age-related macular
      degeneration. The criteria for surgical eligibility included the following: (1) a
      clearly identifiable subfoveal membrane occupying the entire foveal avascular
      zone, (2) a visual acuity of 20/200 or worse, (3) minimal subretinal hemorrhage,
      and (4) an associated exudative macular detachment. Six of the ten patients
      showed visual improvement at one-month and three-month follow-up visits and seven
      showed visual improvement by the six-month examination. All ten maculae remained
      attached without recurrence of subfoveal neovascular membranes throughout the
      follow-up period. These results suggested that surgical excision is a viable
      alternative to laser photocoagulation in patients with subfoveal
      neovascularization in age-related macular degeneration.

PMID- 1371907
TI  - Zinc iodide-osmium tetroxide impregnation of the "tubulo-vesicular system" in
      Tomes' process of the rat incisor ameloblast.
AB  - Zinc iodide-osmium tetroxide (ZIO) is a nonspecific but selective impregnation
      method that visualizes a tubulo-vesicular system in cells. The detailed structure
      and three-dimensional distribution of this ZIO-impregnated system was studied in
      the Tomes' process of secretory ameloblasts in the rat incisor. The ZIO
      impregnated system consisted of an extensive array of smooth membrane-bound thick
      and thin tubules and vesicles. The interconnected thick and thin tubules formed a
      complex "core network" in the central cytoplasm of Tomes' process that enmeshed
      and often surrounded individual secretory granules. From the core network, radial
      branches extended toward the smooth cell membrane of the interdigitating portion
      of Tomes' process. Although the core network and branches frequently appeared
      connected to the secretory granules and the cell membrane, stereo-pair electron
      microscopy failed to show conclusive evidence of such continuity. However, many
      coated vesiclelike structures were attached to the core network and its branches.
      No special relationship was found between interrod and rod secretory sites and
      the tubulo-vesicular network. In thick sections, the ZIO-impregnated tubulo
      vesicular network occupied a considerable volume of cytoplasm. The vinblastine
      labile nature of this network as demonstrated previously (Nanci et al., 1987)
      indicated that the system undergoes rapid and extensive turnover. Considering the
      dynamic nature and sheer volume of the tubulo-vesicular system, we propose that
      it be regarded as a major cell organelle.

PMID- 1371908
TI  - Contrasting effects of alpha, beta, and gamma interferons on nonspecific
      suppressor function in multiple sclerosis.
AB  - Interferons are biological molecules with antiviral, antiproliferative, and
      immunomodulatory actions. Interferon alpha (IFN-alpha) and -beta are potentially
      useful in the treatment of multiple sclerosis (MS). IFN-gamma, in contrast,
      increases the frequency of exacerbations of MS. In this study, we compared the
      effect of recombinant human IFN-alpha, -beta, and -gamma on suppressor function
      in patients with MS. Nonspecific suppressor cell function, measured in a
      concanavalin A suppressor assay, was significantly decreased in 16 patients with
      progressive MS (mean percent suppression +/- SEM, 14.4 +/- 5.5 in patients with
      MS, 33.5 +/- 4.8 in 16 normal subjects; p less than 0.001). Recombinant human IFN
      beta augmented suppressor function in MS to 45.4 +/- 5.1% (p less than 0.001) and
      in control subjects to 56.8 +/- 3.8% (p less than 0.001). Similarly, recombinant
      human IFN-alpha improved suppression in MS to 43.0 +/- 5.6% (p less than 0.001)
      and in control subjects to 51.1 +/- 5.9% (p less than 0.001). In contrast,
      recombinant human IFN-gamma had no effect on suppressor function in patients with
      MS and in control subjects. This study shows that IFN-alpha and -beta augment
      deficient suppressor function in MS, whereas IFN-gamma has no effect on
      suppressor function in the progressive phase of the disease.

PMID- 1371909
TI  - Cyclic AMP metabolism in fragile X syndrome.
AB  - Cyclic AMP (cAMP) metabolism was studied in platelets from a series of 14
      patients with fragile X syndrome (fra X) and 21 control individuals. 1-Isobutyl-3
      methylxanthine was used to inhibit phosphodiesterase and thus measure cAMP
      production, prostaglandin E1 was used to assess receptor-mediated cAMP
      accumulation, and forskolin was used to directly stimulate the catalytic subunit.
      In patients with fra X, basal production was 63% of that of control subjects (p =
      0.019). Prostaglandin E1- and forskolin-stimulated production were 61% (p =
      0.039) and 56% (p = 0.012) of that of control subjects, respectively. cAMP
      production in 8 patients with fra X overlapped the control range, whereas
      measures of production in 6 patients formed a cluster with values lower than any
      of the 21 control subjects assayed, suggesting possible biochemical heterogeneity
      within patients with fra X. Results obtained from the group of patients with fra
      X suggest possible abnormal function or regulation of the catalytic subunit of
      adenylate cyclase in at least a subgroup of patients with fra X. Variability of
      biochemical findings in patients with fra X may reflect the known high
      variability of the clinical syndrome.

PMID- 1371910
TI  - Regenerating and denervated human muscle fibers and satellite cells express
      neural cell adhesion molecule recognized by monoclonal antibodies to natural
      killer cells.
AB  - The monoclonal antibodies anti-Leu-19 and anti-NKH-1 recognize the CD56
      differentiation antigen expressed on natural killer (NK) cells and on a T-cell
      subset. Because CD56 is an isoform of neural cell adhesion molecule (N-CAM), we
      examined its expression on human muscle using antibodies to Leu-19, NKH-1, and
      purified N-CAM in an immunohistochemical, immunoblot, and immunoprecipitation
      study on 70 muscle biopsy specimens from various muscle diseases and on human
      muscle in tissue culture. Anti-Leu-19, anti-NKH-1, and anti-N-CAM had identical
      immunoreactive patterns. In tissue sections, they specifically recognized the
      satellite cells and the regenerating or newly denervated muscle fibers; in tissue
      cultures, they immunoreacted with myoblasts and myotubes; and in the homogenates
      of myopathic muscle and cultured myotubes, they immunoprecipitated the same
      glycoprotein of 145- to 220-kd. The study concludes that (1) the commercially
      available monoclonal antibodies to NK cells, Leu-19 and NKH-1, are
      immunocytochemical markers for the satellite cells and the regenerating or newly
      denervated muscle fibers complementing conventional techniques in the diagnosis
      of patients with neuromuscular disorders; and (2) the CD56 is a common antigen
      shared by NK cells and muscle fibers during certain stages of muscle maturation,
      regeneration, or denervation. When expressed in the muscle, CD56 may facilitate
      the adhesion of cytotoxic lymphocytes to the muscle and play a role in muscle
      fiber injury.

PMID- 1371911
TI  - [Supportive therapy in cancer treatment with colony stimulating factors and
      evaluation of their effect].
AB  - Several tumors are now curable. However, intensive chemotherapy or bone marrow
      transplantation is required for the cure, and thus myelosuppression and resultant
      serious infections are major obstacles for the cure of cancer. G-CSF and M-CSF
      are commercially available in Japan. By strict comparative studies, G-CSF has
      been shown to be a useful drug, shortening the recovery of neutrophils and
      reducing the incidence of documented infections. There have been no convincing
      data that G-CSF stimulates the regrowth of myeloid leukemia in vivo, and thus G
      CSF is safe even in myeloid leukemia, if used with precaution.

PMID- 1371912
TI  - [Detection of estrogen receptor (ER) mRNA by use of reverse transcriptase
      polymerase chain reaction (RT-PCR) assay; comparison with dextran coated charcoal
      (DCC) assay and immunocytochemical assay].
AB  - A new method for estrogen receptor (ER) mRNA was performed on 33 human breast
      tumors, using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay by
      the method of Fuqua et al. In a preliminary experiment using the MCF-7 breast
      tumor cell line, ER/beta-actin ratio was almost same. ER protein was estimated by
      a dextran coated charcoal (DCC) assay and by an ER-immunocytochemical (ER-ICA)
      assay using a specific monoclonal antibody. We found RT-PCR assay correlates with
      ER-ICA assay (r = 0.664, p less than 0.01), whereas no significant correlation
      was seen between RT-PCR assay and DCC assay. These results suggests that RT-PCR
      assay is suitable for detection of ER from small amounts of tissue.

PMID- 1371913
TI  - [A case of advanced ureteral squamous cell carcinoma showing complete response to
      combination chemotherapy with cisplatinum, vindesine, and bleomycin].
AB  - A 56-year-old Japanese female was diagnosed as advanced squamous cell carcinoma
      of the left ureter, stage IV (T4N0M0), and treated with anti-cancer drugs using
      cis-platinum, vindesine, and bleomycin. The tumor vanished after the treatment.
      The specimen after left total nephroureterectomy and hysterectomy showed only
      granulomatous change with necrosis and foreign giant cells but not cancer cells.

PMID- 1371914
TI  - Controlled study of Pseudomonas cepacia and Pseudomonas maltophilia in cystic
      fibrosis.
AB  - In a retrospective study, children with cystic fibrosis who were colonised with
      Pseudomonas cepacia were compared with a control group who were colonised with
      Pseudomonas maltophilia. Out of 216 children with cystic fibrosis seen between
      1983 and 1990, P cepacia was recovered from 13 (median age at colonisation 12.2
      years) and P maltophilia from 23 (median age at first colonisation 6.1 years),
      and both organisms were recovered in five cases. With the exception of two
      patients with P cepacia in whom no other pathogens were found, all the patients
      with P cepacia or P maltophilia had co-colonisation with Pseudomonas aeruginosa.
      The lack of spread of P cepacia to siblings with cystic fibrosis, and the
      relative lack of inpatient contact between colonised and uncolonised patients
      suggest that cross infection is not the sole route whereby patients with cystic
      fibrosis become infected, but the possibility of cross infection cannot be
      excluded from our data. Three patients with P cepacia died, but two of these had
      shown appreciable respiratory deterioration before colonisation with P cepacia;
      there was no evidence of unexpected deterioration in the remainder or in the
      controls with P maltophilia. By 1990, the prevalence of P cepacia was 9/133 (7%)
      and that of P maltophilia was 13/133 (10%), but it was impossible to determine to
      what extent this increase was due to the introduction of the routine use of
      selective media. Further studies are required to establish whether patients with
      and without P cepacia should be segregated.

PMID- 1371915
TI  - Acquired mutism: physiopathy and assessment.
AB  - The speechless patient presents a unique challenge to the clinician working with
      neurologically impaired adults. Acquired speechlessness, or mutism, has been
      associated with a variety of clinical states and syndromes after damage to
      central and peripheral nervous system structures. The intent of this paper is to
      summarize the reported states and syndromes associated with acquired mutism (eg,
      persistent vegetative state, akinesia), and to organize this information in a
      framework for clinical assessment of the speechless patient. For the purpose of
      discussion, speech production is divided into five interrelated processes:
      arousal; cognitive processing; affect and drive; motor initiation, planning,
      programming, and coordination; and execution of movement. Disorders characterized
      by mutism are classified according to the process or processes of speech
      production that primarily are affected. Each subtype of acquired mutism is
      characterized by a cluster of neurologic signs, which has been incorporated into
      a decision-making framework for use in a clinical setting.

PMID- 1371916
TI  - Immunocytochemical labeling of cells in cortical vitreous from patients with
      premacular hole lesions.
AB  - We performed electron immunocytochemical staining for cytokeratins and glial
      fibrillary acidic protein on cortical vitreous obtained at the time of vitrectomy
      from two patients with premacular hole lesions. The specimens were thought to
      represent cortical vitreous because each consisted of a sheet of tissue that, in
      addition to being firmly attached around the foveal lesion, was attached around
      the disc and extended well into the periphery. The specimens contained a moderate
      number of cells and an abundant extracellular matrix. Most of the cells were
      found singly or in small clusters on the surface of the matrix. Preembedding
      immunostaining on one specimen showed several cells that stained for cytokeratins
      and several that stained for glial fibrillary acidic protein. The majority of the
      cells on the matrix appeared to express one of these two intermediate-filament
      proteins. Postembedding immunogold double labeling on both specimens showed that
      most cells were labeled for either glial fibrillary acidic protein or
      cytokeratins, but there were a few cells that unequivocally expressed both
      proteins simultaneously. These data suggest that the cortical vitreous of
      patients with some premacular hole lesions contains retinal pigment epithelial
      and glial cells that may contribute to abnormal vitreoretinal adherence and could
      play a role in macular hole formation.

PMID- 1371917
TI  - 3-amino-1,2,4-triazole inhibits macrophage NO synthase.
AB  - Murine macrophages activated by interferon-gamma and lipopolysaccharide become
      leishmanicidal through a process involving L-arginine-derived nitrogen oxidation
      products. Both nitrite secretion and parasite killing by activated macrophages
      were inhibited by 3-amino-1,2,4-triazole as well as the related compound, 3-amino
      1,2,4-triazine. Moreover, NO synthase activity in cytosolic extracts of activated
      cells was inhibited by both compounds. 4-amino-1,2,4-triazole, an isomer of 3
      amino-1,2,4-triazole, was without effect. Our results suggest that besides its
      known inhibitory effect on catalases and peroxidases, 3-amino-1,2,4-triazole is
      an inhibitor of NO synthase. The resemblance between the tautomeric form of 3
      amino-1,2,4-triazole and the guanidino group of L-arginine, the natural substrate
      for NO synthase, might be responsible for the observed inhibition.

PMID- 1371918
TI  - Cloning of murine and rat vascular cell adhesion molecule-1.
AB  - Vascular cell adhesion molecule-1 (VCAM1) is a member of the immunoglobulin (Ig)
      superfamily which interacts with the integrin very late antigen 4 (VLA4). We have
      cloned the cDNAs for both murine and rat VCAM1 from endotoxin-treated lung
      libraries. Both sequences encode proteins with seven extracellular Ig-like
      domains, which show 75.9% and 76.9% identity, respectively, with human VCAM1.
      Both murine and human cell lines show VLA4-dependent binding to COS cells
      transiently expressing murine and rat VCAM1. Two mAbs, M-K/1 and M-K/2, which
      recognize an antigen on murine bone marrow stromal cell lines, bind to murine
      VCAM1 expressed in COS cells and block VCAM1-dependent adhesion, confirming that
      these mAbs recognize murine VCAM1.

PMID- 1371919
TI  - Purification of nitric oxide synthase from bovine brain: immunological
      characterization and tissue distribution.
AB  - Nitric oxide (NO) synthase (EC 1.14.23) was purified to homogeneity from bovine
      cerebrum. The molecular weight of NO synthase was estimated to be 150 kDa by both
      SDS/PAGE and gel filtration at high salt concentration. For activity, the enzyme
      required NADPH, Ca2+, calmodulin and tetrahydrobiopterin as cofactors. Rabbit
      polyclonal antibody to bovine brain NO synthase reacted with 150 kDa NO synthase
      in various bovine and rat organs, including the brain, pituitary and adrenal
      glands, but not with that in stimulated macrophages, indicating that there are at
      least two immunologically distinct NO synthases.

PMID- 1371920
TI  - Enhancement and alteration of bleomycin-catalyzed site-specific DNA cleavage by
      distamycin A and some minor groove binders.
AB  - The effects of compounds which bind in the DNA minor groove of A.T rich
      sequences, on bleomycin-catalyzed site-specific DNA cleavage were investigated by
      a DNA sequencing technique. Distamycin A enhanced bleomycin-catalyzed DNA
      cleavage in G.C rich sequences such as 5'-GGGGC-3' (under scoring; the cleaved
      nucleotide). The cleavage in such a sequence in the presence of distamycin A was
      greater than that in the absence of distamycin A by as much as about 100 times.
      Neither Hoechst 33258, 4',6-diamidino-2-phenylindole (DAPI) nor berenil caused
      extensive enhancement. The results suggest that the distamycin-induced
      conformational changes of DNA through interactions other than the DNA minor
      groove binding in A.T-rich sequences are specifically suitable for the bleomycin
      action.

PMID- 1371922
TI  - [Adjuvant and drug therapy of chronic pain in the head and neck area].
AB  - Head and neck pain caused of benign or malignant disease reduces remarkable the
      patient's quality of life. In the following are presented adjuvant and
      medicamentous methods for pain control. Surgery, irradiation and chemotherapy aim
      to diminish the tumor extension and reduce algesic transmitting substances in the
      periphery. Nerve blocs, cryoanalgesia and transcutaneous electrical nerve
      stimulation lead to an interruption of the painful spinal reflex arc. Active,
      passive and relaxation exercises prevent from dolorific muscular tensions.
      Psychological treatment, so as relaxation techniques in connection with behavior
      therapy, helps to develop coping strategies. The mainstay of pain relief is
      effective use of analgetics which should be given orally if possible, on a
      regular schedule and on an individualized basis according with the WHO
      guidelines.

PMID- 1371921
TI  - Inhibition of IgE-mediated histamine release by myosin light chain kinase
      inhibitors.
AB  - Wortmannin, a specific inhibitor of myosin light chain kinase (MLCK) blocked IgE
      mediated histamine release from rat basophilic leukemia cell (RBL-2H3) and human
      basophils dose-dependently. Its IC50 was 20 nM for RBL-2H3 cells and 30 nM for
      human basophils. There was complete inhibition at the concentration of 1 microM.
      Wortmannin inhibited partially the A23187 induced histamine release from RBL-2H3
      cells (40% inhibition at 1 microM). This inhibition was not accompanied by any
      significant effect on cytosolic free calcium concentration [( Ca2+]i). KT5926,
      another MLCK inhibitor, inhibited histamine release comparably with wortmannin
      and blocked to some degree the increase of [Ca2+]i in RBL-2H3 cells. Thus, the
      phosphorylation of myosin seems to be involved in signal transduction through Fc
      epsilon RI.

PMID- 1371923
TI  - A proliferation-related constraint on endogenous and interferon-induced 2-5A
      synthetase activity in normal and neoplastic Syrian hamster cells.
AB  - 2-5A Synthetase is one of the most extensively characterized enzymes induced by
      interferon (IFN) and is the central enzyme in a pathway that may be involved in
      the control of cellular proliferation. We examined the activity of this enzyme in
      normal diploid Syrian hamster cells (FC13) and their neoplastically transformed
      derivatives (BP6T); the former cell strain possesses regulated proliferative
      control, while the latter cell line has escaped from this control. A significant
      threefold increase in 2-5A synthetase activity was observed in density-arrested
      versus proliferating FC13 cells, whereas endogenous enzyme activity was uniformly
      low in BP6T cultures. The increase in enzyme activity in FC13 cultures was not
      accompanied by the production of IFN at a detectable level, but was parallelled
      by an increase in the intracellular level of 2',5'-oligoadenylate. IFN treatment
      resulted in a differential induction of enzyme activity depending on the
      proliferative state of FC13 cells. After IFN treatment, BP6T cells and
      subconfluent FC13 cells responded similarly with a fivefold increase in enzyme
      activity, whereas confluent FC13 cells displayed only a 1.4-fold increase. 2-5A
      Synthetase enzyme activity reflected steady-state mRNA levels in BP6T and
      subconfluent FC13 cells. In contrast, a noncoordinate regulation of 2-5A
      synthetase mRNA expression and enzyme activity was detected in confluent FC13
      cells, suggesting that posttranscriptional mechanisms may be involved. The
      different patterns of endogenous and IFN-induced 2-5A synthetase enzyme activity
      in FC13 and BP6T cells found in this comparative study may represent an
      alteration fundamental to the loss of proliferative control in transformed cells.

PMID- 1371925
TI  - HIV-induced, HIV-specific in vitro antibody response by B-cells from HIV
      seropositive individuals.
AB  - OBJECTIVE: Recent studies have shown that B-cells from HIV-infected patients can
      secrete anti-HIV antibodies in vitro and that they represent 20-40% of
      immunoglobulin (Ig)-secreting B-cells in vivo. This study was designed to
      investigate the precise role of HIV in this in vitro antibody production. DESIGN
      AND METHODS: B-cells from HIV-infected patients [asymptomatic, n = 28;
      symptomatic (AIDS), n = 14], from seronegative adult volunteers (n = 22) and
      subjects at high risk for HIV infection (n = 15) were cultured in vitro in the
      presence of pokeweed mitogen, Staphylococcus aureus cowan or HIV, and T-cells or
      interleukins (IL). Non-specific Ig production and specific anti-HIV antibody (Ab)
      production were measured by enzyme-linked immunosorbent and Western blot assays.
      RESULTS: We found that HIV induced a specific response in cultured B-cells from
      seropositive patients, in contrast with cultured B-cells from uninfected normal
      individuals. The characteristics of the HIV-induced response differed from those
      of a spontaneous or a mitogen-induced response. Anti-HIV Ab production was
      optimal on day 8-10, when B-cells were cultured with recombinant IL-2 and
      recombinant interferon-alpha in the presence of infectious virus or recombinant
      gp160 Env protein. The anti-HIV Ab were mainly directed against Env proteins.
      Interaction of HIV with B-cells involved surface IgG but not CD4 antigen.
      Autologous CD8+ T-cells had a non-specific inhibitory effect. Both CD5+ and CD5-
      B-cells produced anti-HIV Ab. No anti-HIV Ab production was observed in B-cells
      from high-risk HIV-seronegative individuals. CONCLUSION: HIV (infectious virus or
      gp160) can induce B-cells from infected patients to secrete specific anti-HIV Ab
      in vitro.

PMID- 1371924
TI  - Immunological variation and immunohistochemical localization of HIV-1 Nef
      demonstrated with monoclonal antibodies.
AB  - OBJECTIVE: To study the immunological and immunohistochemical nature of HIV-1
      Nef. DESIGN: Monoclonal anti-Nef antibodies were generated and used to identify
      antigenic epitopes in Nef, to study immunological cross-reactivity between Nef
      from different isolates and to reveal the subcellular localization of Nef.
      METHODS: Monoclonal antibodies against recombinant HIV-1 Nef protein (BRU
      isolate) were generated in BALB/c mice. The epitope mapping was carried out with
      the use of overlapping 15-20mer lipopeptides linked to a lipid group at the amino
      terminus. Immunoperoxidase method was used for histochemical studies. RESULTS:
      Ten stable antibody-producing clones, mainly of the immunoglobulin (Ig) G1
      subtype, with strong Western blot and enzyme-linked immunosorbent assay
      reactivity toward the recombinant Nef protein, were obtained. The epitopes
      recognized were located on amino-acid sequences 21-41, 31-50, 51-71, 61-80, 151
      170, 161-180, and 171-190. All 10 monoclonal antibodies also reacted with the
      native Nef of HIV-1BRU, and eight reacted with native HIV-1IIIB. Most antibodies
      also reacted with Nef from more divergent HIV-1 strains. In Western blotting, two
      forms of Nef (24 and 27 kDa) were observed with most isolates studied.
      Immunohistochemical staining of HIV-1-infected H9 or MT-4 lymphoid cells
      demonstrated that Nef was expressed mainly in the Golgi complex and at the
      nuclear membrane, but occasionally also in the nucleus. The nuclear localization
      of Nef was especially frequent in the HIV-1-infected MT-4 cells. CONCLUSIONS: Our
      findings suggest that Nef is expressed in two isomorphic forms, and that it may
      also act as a nuclear protein and thus have a direct regulatory function at the
      RNA/DNA level.

PMID- 1371926
TI  - Oligonucleotide therapeutics.
AB  - Recent studies have focused on the ability of oligonucleotides to affect the
      genetic processes of many organisms, including viruses. Hence, oligonucleotides
      may represent a future source of biotechnologically derived compounds of
      therapeutic importance for diseases such as cancer and AIDS.

PMID- 1371927
TI  - Short-term memory and verbal learning with auditory phonological coding defect: a
      neuropsychological case study.
AB  - A patient is described with a rarely reported linguistic syndrome: he could
      repeat words but not nonwords. The patient produced semantic paraphasias in
      repetition and could read both words and nonwords flawlessly. His basic
      difficulties were localized in auditory phonological coding, identifying a
      clinical picture called "phonemic deafness." Short-term memory and verbal
      learning results suggested that a standard, selective short-term memory defect
      can be induced by auditory phonological coding deficits as well as by "pure"
      short-term memory capacity limitation and other phonological deficits. Findings
      also provided evidence that lexical-semantic code can allow normal verbal
      learning.

PMID- 1371929
TI  - Influence of 4 different membrane oxygenators on inflammation-like processes
      during extracorporeal circulation with pulsatile and non-pulsatile flow.
AB  - The influence of four different membrane oxygenators (HF 4000, BOS-CM 50, CML 2,
      Maxima) on leucocyte count, concentrations of PMN-elastase, clotting factor XII,
      AT-III, C1-INH, alpha 2-antiplasmin and C3a was registered before, during and
      after CPB with pulsatile and nonpulsatile flow in 80 male patients aged between
      36 and 67 years. With all systems tested, there was a drop in the concentrations
      of clotting factor XII, AT-III, C1-INH and alpha 2-antiplasmin in the early
      extracorporeal circulation (ECC) phase, exceeding the average hematocrit
      reduction accounted for by dilution. This drop was the least distinct with CML 2
      systems, both with pulsatile and nonpulsatile perfusion, indicating system
      inherent influences. Leucocyte cound and PMN-elastase concentration rose
      significantly during ECC irrespective of oxygenator tested of flow type applied.
      The rise in leucocyte count even continued for about 4 h after ECC. During the
      first 40 min of ECC, these changes were paralleled by a significant rise in C3a
      concentration, suggesting complement activation as a main cause for PMN
      activation. However, there is reason to suppose involvement of further mechanisms
      operating in PMN activation, since the elevated C3a-concentrations began to fall
      off while leucocyte count and PMN-elastase concentrations were still increasing.

PMID- 1371928
TI  - Interaction between secretin and cholecystokinin-octapeptide in the exocrine rat
      pancreas in vivo and in vitro.
AB  - This study investigates the interaction between physiological doses of the
      synthetic gut hormones, cholecystokinin-octapeptide (CCK8) and secretin on
      pancreatic juice secretion in the anaesthetized rat and on amylase secretion and
      Ca2+ and Mg2+ mobilization in isolated pancreatic segments and acinar cells. CCK8
      (150 pmol kg-1 h-1) and secretin (100 pmol kg-1 h-1) evoked marked time course
      increases in pancreatic juice flow, total protein output and amylase secretion in
      the anaesthetized rat when administered separately compared to saline controls.
      Simultaneous intravenous infusion of CCK8 and secretin did not yield either an
      additive response or a potentiation but instead it caused a decrease in secretory
      responses. Administration of either polymyxin B (10(-8) mol kg-1 h-1) or
      staurosporine (10(-8) mol kg-1 h-1), two protein kinase C inhibitors,
      simultaneously with both CCK8 and secretin caused a further decrease in all
      secretory parameters. Superfusing pancreatic segments with either CCK8 (10(-11)
      M) or secretin (10(-11) M) elevated amylase output compared to the smaller
      response with a combination of CCK8 and secretin. Combining staurosporine (10(-6)
      M) with CCK8 and secretin resulted in a further decrease in amylase output. CCK8
      (10(-11) M) evoked a large increase in radiolabelled Ca2+ influx into pancreatic
      segments and elevated cytosolic free Ca2+ concentration ([Ca2+]i) in acinar cells
      loaded with the fluorescent dye, Fura-2. Secretin (10(-11) M) alone had no
      significant effect on Ca2+ mobilization but it markedly attenuated the increases
      in radiolabelled Ca2+ influx and [Ca2+]i elicited by CCK8. In superfused
      pancreatic segments CCK8 (10(-11) M) evoked a net efflux of Mg2+ whereas secretin
      (10(-11) M) induced a net uptake of Mg2+. Combining secretin with CCK8 also
      resulted in a net uptake of Mg2+. The results indicate that both Ca2+ and Mg2+
      mobilization may be associated with the interaction between CCK8 and secretin in
      the rat pancreas.

PMID- 1371930
TI  - Mediastinal pancreatic pseudocyst.
AB  - Pseudocysts of the pancreas are a rare cause of a mediastinal mass. They are
      clinically characterized by the combination of thoracic symptoms (shortness of
      breath, dysphagia, pleural effusions) with complaints in the upper abdominal
      quadrants and weight loss. The diagnosis is usually made by CT scan or MRI
      including upper abdominal views. Internal drainage via an abdominal route
      performed either as cystogastrostomy or cystojejunostomy is the treatment of
      choice.

PMID- 1371931
TI  - Characterization of apolipoprotein B mRNA editing from rabbit intestine.
AB  - Apolipoprotein (apo) B-48 is generated by a unique physiological process.
      Cytidine 6,666 of the apo B primary transcript is posttranscriptionally converted
      to a uridine by an RNA editing mechanism that transforms the codon for glutamine
      2,153 to a termination codon. The editing reaction can be duplicated in a cell
      free extract. In this study, the apo B-48 mRNA editing activity derived from
      partially purified extracts of rabbit enterocytes was characterized. The optimum
      conditions for the editing reaction were determined to be a salt concentration of
      0.125-0.150 M NaCl or KCl, a pH of 8-8.5, and a temperature of 30 degrees C. The
      reaction rate was linear up to 45 minutes and was proportional to the editing
      extract concentration. No metal ion cofactors, DNA or RNA cofactors, or energy
      requirements were identified. At optimum conditions, the reaction followed
      Michaelis-Menten kinetics, with a Km of 0.4 nM for the rabbit RNA substrate. In
      addition, the reaction rate was enhanced by the addition of 25 micrograms/ml
      heparin or 40% glycerol. The characteristics of the editing reaction suggest that
      it is catalyzed by a nucleotide sequence-specific cytidine deaminase that is
      either a single enzyme or a multimeric protein.

PMID- 1371932
TI  - Vampire bat salivary plasminogen activator promotes rapid and sustained
      reperfusion without concomitant systemic plasminogen activation in a canine model
      of arterial thrombosis.
AB  - The efficacy of recombinant vampire bat salivary plasminogen activator (bat-PA)
      as a thrombolytic agent was compared with that of human tissue-type plasminogen
      activator (t-PA) in a canine model of arterial thrombosis. An occlusive thrombus
      was formed in the femoral artery by insertion of a thrombogenic copper coil;
      femoral arterial blood flow was monitored with a Doppler flow meter. Bat-PA and t
      PA, when administered by 5-minute intravenous infusion (14 nmol/kg), reperfused
      seven out of eight and four out of eight dogs, respectively. The median
      reperfusion times in the bat-PA and t-PA groups were 24 and greater than or equal
      to 131 minutes, respectively. The mean reperfusion times (+/- SEM) in the
      recanalized bat-PA- and t-PA-treated dogs were similar (20 +/- 5 and 11 +/- 2
      minutes, respectively, p = NS). Maximal blood flow after reperfusion was greater
      with bat-PA than with t-PA (80 +/- 10% and 41 +/- 15% of control flow,
      respectively, p less than 0.05). Furthermore, the median reocclusion time was
      markedly delayed in the bat-PA group relative to the t-PA group (131 versus 34
      minutes, respectively, p less than 0.05). Plasma fibrinogen and plasminogen were
      not significantly depleted by the administration of t-PA or bat-PA. However,
      plasma alpha 2-antiplasmin activity was moderately depressed in the t-PA group
      relative to the bat-PA group (p less than 0.05). The clearance profile for t-PA
      was monoexponential, with a half-life (t1/2) of 2.4 +/- 0.3 minutes and a mean
      residence time of 3.5 +/- 0.4 minutes. The clearance profile for bat-PA was
      biexponential, with a t1/2 alpha of 0.9 +/- 0.2 minutes, a t1/2 beta of 20.2 +/-
      2.7 minutes, and a mean residence time of 21.3 +/- 4.3 minutes. The steady-state
      volume of distribution displayed by bat-PA was 16-fold greater than that of t-PA.
      Zymography of serial plasma samples from the bat-PA-treated dogs failed to
      demonstrate the apparent generation of a complex between bat-PA and plasminogen
      activator inhibitor-1; the corresponding complex with t-PA was observed in plasma
      samples from the t-PA-treated dogs. The sustained recanalization and improved
      blood flow in the bat-PA group relative to the t-PA group and the avoidance of
      fibrinogenolysis by bat-PA, despite its prolonged mean residence time, suggest
      that bat-PA may be superior to t-PA as a thrombolytic agent.

PMID- 1371933
TI  - Antipeptide antibodies to the carboxy terminal and the DCCD binding region of the
      human mitochondrial ATP synthase beta-subunit.
AB  - Antibodies to defined epitopes on the human ATP synthase would provide a powerful
      tool in the definition of the subunit composition of the enzyme complex and in
      the characterization of any defect in its assembly in diseases associated with
      mitochondrial disorders. Antibodies have been thus raised against synthetic
      peptides, corresponding to two regions on the human ATP synthase beta-subunit:
      the C-terminal region, and a region which includes the two
      dicyclohexylcarbodiimide (DCCD)-reactive glutamic acid residues suggested to be
      involved in the enzyme catalytic activity. The antibodies to the C-terminal
      peptide reacted with the ATP synthase beta-subunit in ELISA, in Western
      immunoblotting and in immunohistochemical experiments, and had the ability to
      immunoprecipitate the enzyme complex. The antibodies to the DCCD-binding region
      peptide did not react to the ATP synthase beta-subunit in its native
      configuration, although reacted well under Western immunoblotting conditions.

PMID- 1371934
TI  - Immunological relatedness of the sarcoplasmic reticulum Ca(2+)-ATPase and the
      Na+,K(+)-ATPase.
AB  - The effect of anti-ATPase antibodies with epitopes near Asp-351 (PR-8), Lys-515
      (PR-11) and the ATP binding domain (D12) of the Ca(2+)-ATPase of sarcoplasmic
      reticulum (EC 3.6.1.38) was analyzed. The PR-8 and D12 antibodies reacted freely
      with the Ca(2+)-ATPase in the native membrane, indicating that their epitopes are
      exposed on the cytoplasmic surface. Both PR-8 and D12 interfered with the
      crystallization of the Ca(2+)-ATPase, suggesting that their binding sites are at
      interfaces between ATPase molecules. PR-11 had no effect on ATPase-ATPase
      interactions or on the ATPase activity of sarcoplasmic reticulum. The epitope of
      PR-11 is suggested to be the VIDRC sequence at residues 520-525, while that of
      D12 at residues 670-720 of the Ca(2+)-ATPase. The use of predictive algorithms of
      antigenicity for identification of potential antigenic determinants in the Ca(2+)
      ATPase is analyzed.

PMID- 1371935
TI  - The use of oligonucleotide probes containing 2'-deoxy-2'-fluoronucleosides for
      regiospecific cleavage of RNA by RNase H from Escherichia coli.
AB  - Protected 2'-deoxy-2'-fluorouridine and 2'-deoxy-2'-fluorocytidine suitable for
      incorporation into oligonucleotides via the phosphoramidite approach have been
      prepared. Five modified and two unmodified oligonucleotides have been synthesized
      to investigate the regiospecific cleavage of a 5S RNA from Escherichia coli by
      RNase H. In order to show whether the modified oligonucleotides are able to
      hybridize with the RNA the physico-chemical properties (melting curves, CD
      spectra) of analogous DNA/oligodeoxyribonucleotide duplexes have been examined.
      The modified oligonucleotides are shown to form stable duplexes with a DNA-matrix
      which exist in an A-like form. Two of the modified probes containing four 2'
      deoxy-2'-fluorocytidines or two 2'-deoxy-2'-fluorouridines direct the splitting
      by RNase H of only one phosphodiester bond of the RNA.

PMID- 1371937
TI  - Tyrosine phosphorylation of biliary glycoprotein, a cell adhesion molecule
      related to carcinoembryonic antigen.
AB  - Biliary-glycoprotein (BGP), a cell adhesion molecule related to carcinoembryonic
      antigen (CEA), has been shown to exist as several alternatively spliced isoforms.
      Here we show that BGPa and BGPb are phosphorylated in the chronic myelogenous
      leukaemia cell line KG-1, which constitutively expresses several BGP isoforms,
      and Chinese hamster LR-73 cells transfected with the cDNAs encoding BGPa and
      BGPb. The phosphorylation can be augmented with the protein tyrosine phosphatase
      inhibitor ammonium vanadate and with TPA (an activator of protein kinase C).
      Phospho-amino acid analysis of phosphorylated BGPs demonstrated that
      phosphorylation occurs on serine, threonine and tyrosine residues.
      Phosphorylation reactions carried out in in vitro membrane preparations from KG-1
      cells revealed a close association of BGP proteins with membrane associated
      protein tyrosine kinases. These observations suggest an association of BGP
      proteins with signal transduction molecules which is regulated by alternative
      splicing of the cytoplasmic domain.

PMID- 1371936
TI  - Rat alpha 1-microglobulin: co-expression in liver with the light chain of inter
      alpha-trypsin inhibitor.
AB  - A 1162 bp rat liver cDNA clone encoding the immunoregulatory plasma protein alpha
      1-microglobulin was isolated and sequenced. The open reading frame encoded a 349
      amino acid polyprotein, including alpha 1-microglobulin, 182 amino acids, and
      bikunin, the light chain of the plasma protein inter-alpha-trypsin inhibitor, 145
      amino acids. The alpha 1-microglobulin/bikunin mRNA was found only in the liver
      when different tissues were examined. Free alpha 1-microglobulin and a
      polyprotein, containing both alpha 1-microglobulin and inter-alpha-trypsin
      inhibitor epitopes, were found in the microsomal fraction from rat liver
      homogenates.

PMID- 1371938
TI  - Inhibition of human exocrine pancreatic secretion by the long-acting somatostatin
      analogue octreotide (SMS 201-995).
AB  - The new long-acting somatostatin analogue octreotide (SMS 201-995) was
      investigated for its influence on secretagogue-stimulated human exocrine
      pancreatic secretion. Eighteen healthy volunteers participated in the study.
      During duodenal intubation with a background stimulation of either secretin 1
      U.kg/h or secretin 1 U.kg/h + ceruletide, 120 ng.kg/h, octreotide was infused at
      doses of 5, 20 and 80 micrograms/h in a placebo-controlled randomized double
      blind crossover trial. Duodenal juice samples were collected in 10-min intervals,
      and amylase, trypsin, chymotrypsin, and bicarbonate were measured in the
      individual fractions. During secretin stimulation, amylase was inhibited between
      41 and 59%, trypsin between 28 and 72%, chymotrypsin between 55 and 70%, and
      bicarbonate between 0 and 31% with 5, 20 and 80 micrograms/h octreotide. During
      secretin and ceruletide stimulation, amylase was significantly inhibited by 84%,
      78%, 81%, trypsin by 76%, 55%, 52%, chymotrypsin by 77%, 55%, 60%, and
      bicarbonate by 25%, 11%, 19% with 5, 20, and 80 micrograms/h octreotide,
      respectively (all decreases P less than 0.05). The long-acting somatostatin
      analogue octreotide was confirmed to be a potent inhibitor of stimulated human
      exocrine pancreatic secretion. The near maximal inhibitory potency of octreotide
      was achieved at a dose of only 5 micrograms/h. This finding may be of value in
      the planning of therapeutic studies with octreotide.

PMID- 1371939
TI  - High-dose aprotinin therapy: a review of the first five years' experience.

PMID- 1371940
TI  - Plasma abnormal prothrombin (PIVKA-II): a new and reliable marker for the
      detection of hepatocellular carcinoma.
AB  - We evaluated the clinical usefulness of a protein induced by vitamin K absence,
      antagonist-prothrombin (PIVKA-II), in detecting hepatocellular carcinoma (HCC)
      specifically in patients with liver cirrhosis, and the possible correlation
      between levels of PIVKA-II and pathological features of HCC. Plasma levels of
      PIVKA-II and alpha-fetoprotein (AFP) were measured in 628 patients with various
      diseases, including 253 with liver cirrhosis and 116 with HCC. PIVKA-II was
      detected (greater than or equal to 0.1 arbitrary unit/mL) in 54.3% of HCC and the
      concentration showed a positive correlation with the tumour size. As a screening
      test for the detection of HCC, PIVKA-II produced values comparable with those of
      AFP with a sensitivity, specificity and validity of 52.8, 98.8 and 51.6%
      respectively. Sixteen of 45 patients (37%) with HCC who had low AFP (less than
      100 ng/mL) levels were positive for PIVKA-II. No apparent relationship, however,
      could be found between the levels of PIVKA-II and the aetiology or pathological
      findings of HCC. These results suggest that PIVKA-II can be a reliable marker for
      detecting HCC in patients with liver cirrhosis.

PMID- 1371941
TI  - The genes for the inter-alpha-inhibitor family share a homologous organization in
      human and mouse.
AB  - Inter-alpha-inhibitor (I alpha I) and related molecules in human are comprised of
      three evolutionarily related, heavy (H) chains and one light (L) chain, also
      termed bikunin. The latter originates from a precursor molecule that is cleaved
      to yield the bikunin and another protein designated alpha-1-microglobulin (A1m).
      The four H and L chains are encoded by four distinct genes designated H1, H2, H3,
      and L. The L and H2 genes are localized onto human chromosomes (chr) 9 and 10,
      respectively, whereas the H1 and H3 genes are tandemly arranged on chr 3. Mouse
      poly(A)+ RNAs or endonuclease-restricted mouse DNA were analyzed by standard and
      pulsed-field gel electrophoresis (PFGE) techniques in agarose gels and blot
      hybridized with human H1, H2, H3 or L cDNA probes. The variable sized transcripts
      and unique restriction fragment patterns detected with each probe indicate that
      four genes, including one common L gene for A1m and bikunin also exist in mouse.
      The co-migration of H1- and H3-hybridizing fragments on PFGE suggests that the
      mouse H1 and H3 genes are also tandemly arranged. An Msp I restriction fragment
      length polymorphism (RFLP) in the mouse L gene (proposed symbol, Intin-4) links
      this gene to other genes already mapped at mouse Chr 4 near the brown (b) locus,
      a homologous region to the human chr 9q32-34 band where the human I alpha I L
      gene is located. Therefore, a similar number and arrangement of I alpha I genes
      is found in mouse and human, including the triplication of an H gene ancestor.
      These results point to an ancient origin of this complex set of genes.

PMID- 1371942
TI  - Characterization of peripheral blood CD8/11b cells in bone marrow transplant
      recipients. III. Subsets of CD8/11b cells differentially regulate immunoglobulin
      production.
AB  - Recovering bone marrow transplant (BMT) recipients have 20-70% circulating
      lymphocytes which co-express CD8 and CD11b (normals = 5-15%). These CD8/11b cells
      comprise at least two subpopulations distinguished by their expression of CD3.
      The CD3+ CD8/11b cells are T lymphocytes which exhibit in vitro suppressor
      activity (Ts); the CD3- CD8/11b cells express CD16 and are natural killer (NK)
      cells. In this study, we investigated whether such cells influenced circulating
      levels of IgA and IgM in 18 BMT recipients who each had greater than 30%
      circulating CD8/11b cells. We observed that in all patients whose CD8/11b cells
      were Ts lymphocytes (7/7) IgM and IgA levels were less than 10% of normal. Among
      those patients whose CD8/11b cells were NK cells (n = 11), two groups were
      distinguished. In one group (n = 5), less than 35% of patient NK cells expressed
      CD57 and serum levels of IgM and IgA were less than 10% of normal. In the second
      group (n = 6) greater than 60% of the NK cells expressed CD57 and serum levels of
      IgM and IgA were normal. In summary, our data indicate that BMT recipients have
      at least three distinct subsets of CD8/11b lymphocyte populations which may
      differentially regulate IgM and IgA production in vivo.

PMID- 1371943
TI  - Making and using medical slides.
AB  - Despite a great proliferation of new media and technologies, the traditional live
      lecture is still highly regarded among scientists as an effective means of
      teaching and communication--and the 'lantern slide' remains the most popular
      lecturer's aid. Here are a few thoughts on how to create good slides and how to
      make the best use of them.

PMID- 1371945
TI  - The pharmacology of local anesthetics--a review of the literature.
AB  - In the nineteenth century, some natives of Peru noticed circumoral numbness,
      euphoria and analgesia after chewing the leaves of the Erythroxylen coca bush. By
      1850, cocaine was isolated from the plant, marking the start of the local
      anesthetic era in clinical medicine. Over the past 50 years, many synthetic local
      anesthetics have been developed which have fewer side effects, increased
      specificity of action and a wider margin of safety than cocaine. Currently, local
      anesthetics are used topically, for local infiltration; and intravenously, for
      peripheral nerve blockade, for sympathetic blockade, as well as for epidural and
      intrathecal use. Although the route of administration may affect pharmacokinetics
      and pharmacodynamics, it is the purpose of this article to review the general
      pharmacology of this entire range of clinically useful compounds.

PMID- 1371944
TI  - Detection of psychiatric disorders among Asian patients presenting with somatic
      symptoms.
AB  - Patients from India and Pakistan frequently communicate their emotional distress
      in terms of somatic sensations and somatic metaphors. Language and cultural
      difficulties may prevent recognition of psychiatric disorders. A new
      questionnaire is described, to assist identification of psychiatric disorders
      among Asian patients who present with somatic symptoms.

PMID- 1371947
TI  - Cultured human thymocytes lacking CD2 and CD11a/CD18 antigens are functional and
      adhere to endothelial cells via CD56 or CDw49d molecules.
AB  - The preferential growth of CD3-CD2-CD11a/CD18- thymocytes was obtained by
      stimulation of CD2-CD3- thymic cells with low doses of PMA (0.5 ng/ml) and
      subsequent culture in the presence of recombinant interleukin-2 (100 U/ml). After
      2-3 weeks, CD3-CD2-CD11a/CD18- thymocytes represented 40-60% of the total
      proliferating cells. Highly purified CD3-CD2-CD11a/CD18- cell populations were
      obtained by depletion of the CD11a/CD18+ thymocytes by immunomagnetic beads.
      Moreover, these populations proliferated for 2-5 weeks and did not change their
      surface phenotype. It is of note that these cells, despite the lack of CD2 and
      CD11a/CD18 adhesion molecules, could bind to umbilical vein endothelial cells as
      efficiently as did CD3+CD2+CD11a/CD18+ thymocytes. Furthermore we demonstrate
      that (a) CD56 molecule is involved in the adhesion of CD3-CD2-CD11a/CD18- thymic
      cells, but not of peripheral CD3-CD56+ lymphocytes, to untreated or IFN-gamma-
      and/or TNF-alpha-treated endothelium, (b) anti-CDw49d mAb could inhibit the
      adhesion of this thymus-derived population to either IFN-gamma- or TNF-alpha
      treated endothelial cells but not to untreated endothelium, and (c) CD56 antigen
      expressed by these cultured thymocytes has a sialic acid content different from
      that of peripheral lymphocytes. Indeed, isoelectrofocusing analysis showed that
      CD56 molecule expressed on CD3-CD2-CD11a/CD18- thymocytes displayed an
      isoelectric point (pI 5.0) different from that of CD56 antigen expressed by
      peripheral NK cells (pI 4.7 and 5.4). Further, we noted that CD56 antigen showed
      the same pI 5.8 after desialylation obtained using neuraminidase treatment.
      Finally, CD3-CD2-CD11a/CD18- thymocytes mobilized Ca2+ and released TNF-alpha and
      IFN-gamma after treatment with lectins.

PMID- 1371946
TI  - Subcutaneous narcotic infusions for cancer pain: treatment outcome and guidelines
      for use.
AB  - OBJECTIVE: To provide guidelines for the institution and maintenance of a
      continuous subcutaneous narcotic infusion program for cancer patients with
      chronic pain through an analysis of the narcotic requirements and treatment
      outcomes of patients who underwent such therapy and a comparison of the costs of
      two commonly used infusion systems. DESIGN: Retrospective study. SETTING:
      Tertiary care facilities and patients' homes. PATIENTS: Of 481 patients seen in
      consultation for cancer pain between July 1987 and April 1990, 60 (12%) met the
      eligibility criteria (i.e., standard medical management had failed, and they had
      adequate supervision at home). INTERVENTION: Continuous subcutaneous infusion
      with hydromorphone hydrochloride or morphine started on an inpatient basis and
      continued at home whenever possible. OUTCOME MEASURES: Patient selectivity,
      narcotic dosing requirements, discharge rate, patient preference for analgesic
      regimen, side effects, complications and cost-effectiveness. RESULTS: The mean
      initial maintenance infusion dose after dose titration was almost three times
      higher than the dose required before infusion (hydromorphone or equivalent 6.2 v.
      2.1 mg/h). Eighteen patients died, and the remaining 42 were discharged home for
      a mean of 94.4 (standard deviation 128.3) days (extremes 12 and 741 days). The
      mean maximum infusion rate was 24.1 mg/h (extremes 0.5 and 180 mg/h). All but one
      of the patients preferred the infusion system to their previous oral analgesic
      regimen. Despite major dose escalations nausea and vomiting were well controlled
      in all cases. Twelve patients (20%) experienced serious systemic toxic effects or
      complications; six became encephalopathic, which necessitated dose reduction,
      five had a subcutaneous infection necessitating antibiotic treatment, and one had
      respiratory depression. The programmable computerized infusion pump was found to
      be more cost-effective than the disposable infusion device after a break-even
      point of 8 months. CONCLUSIONS: Continuous subcutaneous infusion of opioid drugs
      with the use of a portable programmable pump is safe and effective in selected
      patients who have failed to respond to standard medical treatment of their cancer
      pain. Dose titration may require rapid dose escalation, but this is usually well
      tolerated. For most communities embarking on such a program a programmable
      infusion system will be more cost-effective than a disposable system.

PMID- 1371948
TI  - The major rheumatoid factor cross-reactive idiotype is dominantly expressed by
      Staphylococcus aureus Cowan strain I-activated CD5+ control B cells.
AB  - Some seropositive (RF+) and seronegative (RF-) rheumatoid arthritis (RA) patients
      selectively express high concentrations of the major RF cross-reactive idiotype
      (RCRI) in their sera and generate high frequencies of RCRI+ pokeweed mitogen
      (PWM)-induced plasma cells from their peripheral blood mononuclear cells (PBM).
      To determine if normal individuals can express RCRI in vitro, B cells from
      controls were activated with Staphylococcus aureus Cowan strain I (SAC) bacteria
      to identify RCRI and RF production. In addition, we studied the relationship of
      RCRI expression with the subset of B cells bearing CD5. Control CD5+ B cells are
      responsible for RCRI expression following SAC activation. We also observed that
      RCRI is dominantly expressed by control SAC-induced B cells in frequencies
      comparable to that expressed by some RA and juvenile rheumatoid arthritis
      patients' PBM activated by PWM. Therefore, the frequency of RCRI+ B cells in
      control and arthritis patients' PBL may be similar, or the selection and/or
      regulation of RCRI+ B-cell expression in vitro and in vivo may be different in
      arthritis patients compared to normal individuals.

PMID- 1371949
TI  - Differential expression of a CD45R epitope(6B2) on murine CD5+ B cells: possible
      difference in the post-translational modification of CD45 molecules.
AB  - Although murine peritoneal B cells were homogenously positive for an epitope Lp
      2, coded for by the alternative exon 4 of the CD45 gene, they were heterogenous
      with respect to the expression of another CD45R epitope, 6B2, of unknown exon
      dependency. While the majority of 6B2-high peritoneal B cells was composed of CD5
      B cells, those with low or negative 6B2 were CD5+ B cells. Both 6B2+ and 6B2-
      peritoneal B cells expressed mainly the same largest CD45R transcripts, with all
      three alternative exon (4, 5, and 6) sequences. Further, a CD5+ B lymphoma cell
      line, BCL-1, which was found to be Lp-2+6B2- also had the largest isoform of
      CD45R molecules with all three alternate structures. Although enzyme digestion
      studies suggested that the 6B2 epitope resides in protein, not in sugar
      structures, it is likely that a post-translational modification of CD45R
      molecules is responsible for the presence or absence of 6B2 epitope expression on
      peritoneal CD5+ B cells. This event may be related to the differential role of
      CD45R molecules in regulating lymphocyte function.

PMID- 1371950
TI  - Differential effects of cyclosporin A on diverse B cell activation phenomena
      triggered by crosslinking of membrane IgM.
AB  - Cyclosporin A (CsA) was tested for its modulatory effects on the mIgM-mediated
      signaling of G0*-associated increases in class II MHC expression, G1-related RNA
      synthesis, and S phase-related DNA synthesis in human B cells. While CsA at
      concentrations as low as 10-100 ng/ml could completely ablate anti-IgM-induced
      DNA synthesis, earlier G1-associated RNA synthesis was only partially inhibited,
      and signaling of increased membrane class II MHC expression was unaffected by up
      to 1000 ng/ml of CsA. Similar phenomena were observed in a clonal population of
      leukemic B lymphocytes susceptible to anti-IgM-mediated activation in the absence
      of T cells and T cell factors indicating (a) that the inhibitory effects are not
      due to CsA-mediated suppression of cytokine production by contaminating T cells,
      and (b) that the varying effects of CsA on the diverse activation phenomena do
      not reflect B cell subpopulation diversity. Pulsing studies revealed that while
      maximal suppression of anti-IgM-induced G1-associated RNA synthesis required CsA
      at culture initiation, near maximal suppression of DNA synthesis occurred when
      CsA, or soluble human IgM, was added up to 30 hr after the initial exposure of
      resting B cells to the anti-IgM ligand. These latter findings are consistent with
      the possibility that the CsA-mediated suppression of S phase entry is due to the
      inhibition of a signaling event proximal to mIgM ligation which must be
      repeatedly initiated throughout the first 30 hr of activation.

PMID- 1371951
TI  - Fc gamma RII/CD32-negative human Langerhans cells may be responsible for the
      immunostimulatory activity of freshly isolated epidermal cells.
AB  - Cultured murine and human epidermal Langerhans cells (LC) undergo a phenotypical
      and functional maturation process. In fact, they loose Fc gamma RII and Birbeck
      granules, increase HLA-DR expression, and become potent accessory cells for
      allogeneic MLR. However, resident/freshly isolated human epidermal LC represent a
      phenotypically heterogeneous cell population. Indeed, a subset of CD1a+ LC lacks
      Birbeck granules, is Fc gamma RII/CD32-, and strongly expresses HLA-DR and the
      RFD1 antigen that is considered to be specific for interdigitating cells. In the
      present study the functional capacity of this Fc gamma RII/CD32- CD1a+ LC subset
      was investigated in MLR assays by comparing the stimulatory activity of freshly
      isolated crude epidermal cells (EC) with that of freshly isolated EC depleted in
      CD1a+ or in Fc gamma RII+ cells. Thereby, we observed that crude EC stimulated
      allogeneic PBMC while the removal of CD1a+ cells abrogated this stimulation.
      However, crude EC depleted in Fc gamma RII/CD32+ cells still exhibited a
      stimulatory capacity that was at least equal to that of crude EC. Taken together,
      these data suggest that among resident human epidermal LC there exists a subset
      of phenotypically and functionally more differentiated cells that may be solely
      responsible for the stimulatory capacity of freshly isolated crude EC.

PMID- 1371952
TI  - Changes of expression of endogenous sugar receptors by polymorphonuclear
      leukocytes after prolonged anaesthesia and surgery.
AB  - Anaesthesia and surgery are known to depress granulocyte function in the early
      postoperative period, leading to deterioration of the immune defence against
      infection. Carbohydrate-lectin interactions may play an important role in the
      activities of phagocytic cells in that they facilitate initial host defence in
      the event of microbial antigenic challenge. A panel of biotinylated
      (neo)glycoproteins (chemically glycosilated carrier proteins) was used to detect
      endogenous carbohydrate-binding receptors /lectins/, on peripheral blood
      polymorphonuclear leukocytes of patients undergoing prolonged anaesthesia for
      replantation surgery. Four hours after induction of anaesthesia, a progressive
      decline of expression of endogenous sugar receptors on granulocytes was detected
      using the labelled (neo)glycoproteins lactose-BSA, N-acetyl-D-glucosamine-BSA, D
      mannose-BSA, sialic-acid-BSA and D-xylose-BSA. Concomitant changes in peripheral
      white blood cell counts and the lack of depression in the absence of general
      anaesthetic agents suggested the existence of a possible relationship between
      reduced expression of (neo)glycoprotein receptors to impaired granulocyte
      function and anaesthetic-induced immunodepression.

PMID- 1371953
TI  - High antibody levels to the mycobacterial fibronectin-binding antigen of 30-31 kD
      in tuberculosis and lepromatous leprosy.
AB  - Immunoblot assays showed that mycobacterial fibronectin-binding antigens are
      important targets of the humoral immune response in tuberculosis and leprosy.
      Using culture filtrate antigens of Mycobacterium tuberculosis, strong reactivity
      with the fibronectin-binding of 30-31 kD (Fn 30-31) was demonstrated in 55.9% of
      tuberculosis sera and in 56.5% of lepromatous leprosy sera. Sera from patients
      with tuberculoid leprosy and control sera gave very weak binding. Reactivity of
      tuberculosis and lepromatous leprosy sera with the fibronectin-binding antigen of
      58-60 kD (Fn 58-60) was less conspicuous. The ability to react with fibronectin
      of the antigens of 58-60 and 30-31 kD was demonstrated by parallel labelling with
      a fibronectin-biotin conjugate. Fn 30-31 was purified to homogeneity by a two
      step procedure and used for ELISA. Positive titres were found in 63% out of 65
      tuberculosis sera and in 60.5% out of 43 lepromatous leprosy sera. Antibody
      titres in lepromatous leprosy sera were higher than in tuberculosis sera. Our
      observations indicate indirectly that M. leprae possess a highly immunogenic
      molecule homologous to M. tuberculosis Fn 30-31, which elicits a high antibody
      response in lepromatous leprosy but not in tuberculoid leprosy. In this
      investigation, direct evidence for the presence of this antigen in M. leprae was
      obtained by immunochemistry of lepromatous leprosy lesions with a monospecific
      antibody raised against M. tuberculosis Fn 30-31.

PMID- 1371954
TI  - Specific inhibition of mRNA accumulation for lymphokines in human T cell line
      Jurkat by mycobacterial lipoarabinomannan antigen.
AB  - The immunomodulatory effect of Mycobacterium tuberculosis-derived
      lipoarabinomannan (LAM) on mitogen/antigen-induced expression of mRNAs for a
      number of cytokines in human monocytic cell line Mono-Mac-6 and in T cell line
      Jurkat was investigated. Interestingly, LAM exhibited a down-regulatory effect on
      the accumulation of mRNAs for IL-2, IL-3, granulocyte-macrophage colony
      stimulating factor (GM-CSF), and IL-2 receptor alpha (IL-2R alpha) in T cells co
      stimulated with phytohaemagglutinin-P (PHA) and 4 beta-phorbol-12-myristyl-13
      acetate (PMA). In human Mono-Mac-6 cells. LAM has a weak inhibitory effect on the
      lipopolysaccharide (LPS)-induced mRNA accumulation for IL-1 beta, a slight
      stimulatory effect on mRNAs accumulation for IL-8 and tumour necrosis factor
      alpha (TNF-alpha), but clearly no effect on mRNA accumulation for intercellular
      adhesion molecule-1 (ICAM-1). These findings imply that LAM may contribute to the
      immunologic defects associated with a number of mycobacterial infections by
      modulating these mediators.

PMID- 1371956
TI  - Safety and efficacy of repeated sequential administrations of Re-186(Sn)HEDP as
      palliative therapy for painful skeletal metastases. Initial case reports of two
      patients.
AB  - Single intravenous injections of 30 to 35 mCi (1,110 to 1,295 MBq) of Re
      186(Sn)HEDP previously have been shown to result in palliation of painful
      skeletal metastases from prostate cancer. There are no reports of patients
      receiving repetitive Re-186(Sn)HEDP therapy. We have followed two such patients
      who received multiple (five to seven) injections of Re-186(Sn)HEDP at 2-month
      intervals. Each experienced a sustained decrease in both pain and analgesic
      intake. The only evident clinical or biochemical toxicity was a mild progressive
      decline in their total platelet counts.

PMID- 1371955
TI  - Structural properties of the glycoplasmanylinositol anchor phospholipid of the
      complement membrane attack complex inhibitor CD59.
AB  - CD59, the membrane regulator of autologous C5b-9 channel formation, exhibits
      variable sensitivity to cleavage by phosphatidylinositol-specific phospholipase C
      (PI-PLC), an enzyme that releases glyco-inositolphospholipid (GPI)-anchored
      proteins from cell surfaces. To determine whether the GPI-anchor phospholipid of
      CD59 is similar to that of decay-accelerating factor (DAF) and whether variation
      in its structure underlies its variable enzyme susceptibility, the GPI anchors of
      the two proteins expressed on erythrocytes, polymorphonuclear and mononuclear
      leucocytes were compared in situ and after purification. Flow cytometric analyses
      of PI-PLC-treated cells showed parallel cell type specific release of both
      proteins as a function of enzyme concentration. Non-denaturing PAGE analyses of
      alkaline/hydroxylamine-treated proteins (affinity-purified from [125I]-surface
      labelled cells) provided evidence for (i) comparable proportions of GPI-anchor
      acylation, and (ii) alkali-resistant rather than alkali-sensitive lipid
      substituents in erythrocytes. These findings argue that the differential C5b-9
      sensitivity that distinguishes paroxysmal nocturnal haemoglobinuria II and III
      erythrocytes does not derive from expression of CD59 molecules with alternative
      GPI-anchor phospholipid structures.

PMID- 1371957
TI  - [Indications for endobronchial therapy].

PMID- 1371958
TI  - Stimulation by TGF beta of chick embryo fibroblasts--inhibition by an IGFBP-3.
AB  - The multiple effects of TGF beta on cell proliferation are not well understood.
      Our results show that TGF beta was a good but transient mitogen for chick embryo
      fibroblasts. DNA synthesis was three- to fourfold increased, even at high
      concentrations of TGF beta. We did not show a bimodal effect. An inhibitor of
      cell growth, that inhibits 100% of stimulation induced by serum in CEF, was
      purified to homogeneity from medium conditioned by mouse 3T3 cells. This
      inhibitor has been shown to be an IGF-binding protein (mIGFBP-3). In the present
      work, this mIGFBP-3 inhibited the TGF beta stimulation by about 50%, while the
      stimulation induced by PDGF or insulin was not inhibited by mIGFBP-3.
      Furthermore, TGF beta stimulation, in the presence of a high concentration of
      insulin in conditions which would saturate IGF receptors, was not significantly
      inhibited by mIGFBP-3. All together these results suggest that a part of the
      mitogenic effect of TGF beta may be through increasing IGF secretion and
      eventually other growth factors such as PDGF (as suggested previously).

PMID- 1371959
TI  - Transdifferentiation of murine squamous vaginal epithelium in proestrus is
      associated with changes in the expression of keratin polypeptides.
AB  - The superficial layers of the stratified squamous epithelium of the murine vagina
      undergo transdifferentiation into cuboidal mucinous cells during the proestrus
      phase of the normal estrous cycle. In contrast to their squamous progenitor cells
      which have the cytoskeletal characteristics of squamous epithelium, mucinous
      cells express keratin polypeptides typical of simple nonstratified epithelia.
      Accordingly, the transdifferentiation of squamous cell into mucinous cells
      involves not only a change in cell morphology but also a switch in the expression
      of keratin polypeptides. These data indicate that the stratified squamous cells
      of the vagina are not terminally differentiated and their phenotype can be
      hormonally modulated.

PMID- 1371960
TI  - Induction of tyrosinase in human melanoma cells by L-tyrosine phosphate and
      cytochalasin D.
AB  - Pigmentation of RVH 421 human melanoma cells is induced when cell division is
      inhibited by cytochalasin D or L-tyrosine phosphate. Increased pigmentation
      correlates with increased tyrosinase activity when this is monitored over a time
      course. Parallel measurements show that the amount of tyrosinase mRNA correlates
      with enzyme activity in cells growing without these additives. In contrast, in
      the presence of cytochalasin D or L-tyrosine phosphate, the increase in amount of
      tyrosinase mRNA is not sufficient to account for the increase in enzyme activity,
      indicating that these compounds act mainly at a post-transcriptional level.

PMID- 1371962
TI  - Assembly and nuclear transport of the U4 and U4/U6 snRNPs.
AB  - We have analyzed the assembly of the spliceosomal U4/U6 snRNP by injecting
      synthetic wild-type and mutant U4 RNAs into the cytoplasm of Xenopus oocytes and
      determining the cytoplasmic-nuclear distribution of U4 and U4/U6 snRNPs by CsCl
      density gradient centrifugation. Whereas the U4 snRNP was localized in both the
      cytoplasmic and nuclear fractions, the U4/U6 snRNP was detected exclusively in
      the nuclear fraction. Cytoplasmic-nuclear migration of the U4 snRNP did not
      depend on the stem II nor on the 5' stem-loop region of U4 RNA. Our data provide
      strong evidence that, following the cytoplasmic assembly of the U4 snRNP, the
      interaction of the U4 snRNP with U6 RNA/RNP occurs in the nucleus; furthermore,
      cytoplasmic-nuclear transport of the U4 snRNP is independent of U4/U6 snRNP
      assembly.

PMID- 1371961
TI  - The role of the IGF1 receptor in the regulation of cdc2 mRNA levels in
      fibroblasts.
AB  - The levels of cdc2 mRNA increase when quiescent cells are stimulated by growth
      factors. In BALB/c 3T3, both platelet-derived growth factor and insulin-like
      growth factor 1 (IGF-1) are required to increase cdc2 mRNA levels. In p6 cells,
      which constitutively overexpress the IGF-1 receptor, IGF-1 is sufficient. The
      importance of the IGF-1/IGF-1 receptor interaction in regulating the levels of
      cdc2 mRNA was further confirmed by showing that an antisense oligodeoxynucleotide
      to the IGF-1 receptor RNA inhibited the IGF-1-mediated increase.

PMID- 1371963
TI  - Kinetics of rG-CSF-induced neutrophilia in mice.
AB  - To evaluate the mechanism of neutrophilia by granulocyte colony-stimulating
      factor (G-CSF), kinetic studies with tritiated thymidine ([3H]TdR) were performed
      in mice. G-CSF increased the number of circulating metamyelocytes and band and
      segmented neutrophils after the daily injection of G-CSF. The production of
      neutrophils has been estimated from the number of postmitotic neutrophils and the
      marrow transit time of [3H]TdR-labeled neutrophils on day 4 of daily G-CSF
      injection. The number of postmitotic neutrophils was determined by the radioiron
      dilution method and by the neutrophil and erythroid ratio in bone marrow smears.
      The mean values for marrow postmitotic neutrophils in the G-CSF-treated group and
      the controls were 71 +/- 50 x 10(7) cells and 9.3 +/- 4.2 x 10(7) cells (mean +/-
      SD), respectively. The mean marrow transit time derived from myelocyte
      metamyelocyte transition time and the emergence of [3H]TdR-labeled cells into the
      peripheral blood was 45 h in the G-CSF group and 116 h in the controls. Thus, the
      daily neutrophil turnover was estimated to be 38 x 10(7) cells/day and 1.9 x
      10(7) cells/day, respectively. Our results suggest that C-CSF markedly increases
      the neutrophil precursors and shortens the transit time in the mitotic and
      postmitotic pool.

PMID- 1371964
TI  - Interleukin 1-induced sequential myelorestoration: dynamic relation between
      granulopoiesis and progenitor cell recovery in myelosuppressed mice.
AB  - The myelorestorative effect of recombinant human interleukin 1 alpha (IL-1 alpha)
      was studied in mice treated with anticancer drugs. The treatment of mice with 5
      fluorouracil (5-FU; 250 mg/kg body weight) or cyclophosphamide (CPA; 100 mg/kg)
      considerably decreased bone marrow or splenic colony-forming units in culture
      (CFU-C) or neutrophils in blood. The daily administration of IL-1 alpha (100
      ng/mouse/day) after 5-FU treatment markedly accelerated the recovery of bone
      marrow CFU-C. This increase was followed by the recovery of splenic CFU-C and
      neutrophils in blood. In the CPA-treated mice the recovery of bone marrow CFU-C
      over the normal level was observed regardless of the administration of IL-1 alpha
      3 days after CPA treatment. The daily administration of IL-1 alpha after CPA
      treatment markedly increased splenic CFU-C or neutrophils over the normal level
      following the increase of bone marrow CFU-C. Thus, in both 5-FU- and CPA-treated
      mice, the increase of bone marrow CFU-C after the administration of IL-1 alpha
      was observed several days earlier than the increase of splenic CFU-C and
      neutrophils in blood. The increase of splenic CFU-C and neutrophils in blood was
      observed concomitantly. The experiments, in which effective timing of IL-1 alpha
      injection was examined, indicated that the administration of IL-1 alpha within a
      few days after treatment with anticancer drugs was necessary for the accelerated
      recovery of bone marrow progenitor cells. On the other hand, the effective
      recovery of splenic progenitor cells and peripheral neutrophils required the
      administration of IL-1 alpha after the increase of bone marrow progenitor cells.
      Thus, the administration of IL-1 alpha daily or every other day was the most
      effective for recovery from myelosuppression induced by anticancer drugs.

PMID- 1371965
TI  - Recombinant interleukin 3 induces interleukin 2 receptor expression on early
      myeloid cells in normal human bone marrow.
AB  - Human interleukin 3 (IL-3) is a multipotential cytokine that supports the growth
      of early hematopoietic progenitors and promotes their response to other, later
      acting cytokines. We found that IL-3 was able to induce the expression of
      interleukin 2 (IL-2) receptor (IL-2R) (CD25) on a subset of early myeloid cells
      in normal human bone marrow that had been first depleted of mature hematopoietic
      cells and E-rosette-positive T cells by treatment with soybean lectin and sheep
      erythrocytes (SBA-E-BM). Immunofluorescence analysis revealed that the CD25+
      cells were contained almost entirely within the lymphoblastoid gate of the IL-3
      cultured marrow. CD25 was undetectable on freshly isolated marrow and less than
      10% CD25+ cells could be detected following liquid culture at 37 degrees C in the
      presence of 10% human serum, 10% fetal calf serum, or under serum-free
      conditions. Addition of IL-3 (100 U/ml) significantly increased the expression of
      CD25 to 37%, 31%, and 24%, respectively. CD25 could also be induced by
      granulocyte-macrophage colony-stimulating factor (GM-CSF), but no IL-2R was
      detectable following exposure to granulocyte colony-stimulating factor (G-CSF),
      macrophage colony-stimulating factor (M-CSF), interleukin 1 (IL-1), interleukin 4
      (IL-4), or IL-2. Expression of CD25 was dependent on the dose of IL-3 or GM-CSF
      added and was maximal within 24 h of exposure. Two-color immunofluorescence
      analysis demonstrated that CD25 was not expressed by cells of lymphoid lineage or
      by mature monocytes, but rather was present on cells that coexpressed CD13, CD33,
      CD34, MY8, and HLA-DR, and that lacked CD14 or CD11b, thus placing the CD25+
      cells at or near the myeloblast stage of differentiation. An identical phenotype
      was found for CD25+ cells induced by GM-CSF. Cycloheximide completely inhibited
      the IL-3-induced expression of CD25, indicating the necessity for protein
      synthesis, and although most of the CD25+ cells were in G0/G1 phase, 25% of the
      cells were in S or G2M phase, indicating that receptor expression was not cell
      cycle dependent. The p75 chain of IL-2R was not detected on the CD25+ cells. IL-3
      was also found to directly induce CD25 in greater than 46% of SBA-E-BM enriched
      for CD34+ cells by panning. Consistent with the expression of only p55 IL-2R, the
      functional activity of IL-2 on enriched CD34+ cells exposed to IL-3 could not be
      demonstrated in either granulocyte-macrophage colony-forming unit (CFU-GM) assays
      or proliferation assays.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1371966
TI  - Colony-stimulating activity in the serum of patients with hemopoietic
      malignancies after intensive chemotherapy/radiotherapy: its augmentation by GM
      CSF in vivo and interleukin 4 in vitro.
AB  - Colony-stimulating activity (CSA) in the serum of patients with hematological
      malignancies increased substantially after intensive therapy with
      cyclophosphamide/busulfan, cyclophosphamide/total body irradiation, or
      melphalan/total body irradiation. This was not dependent on patients receiving
      allogeneic bone marrow transplantation (ABMT) or autologous bone marrow rescue
      (ABMR). In 44 of 62 patients CSA was maximum approximately 7 days after
      chemotherapy/radiotherapy, whereas in 18 of 62 patients CSA was maximum between 9
      and 20 days after therapy and decreased thereafter. The time course of CSA was
      not dependent on disease and was not affected by recombinant human granulocyte
      macrophage colony-stimulating factor (rhGM-CSF) given as a continuous infusion
      for 14 days after therapy; however, serum from patients receiving rhGM-CSF
      produced significantly more colonies from donor bone marrow than serum from
      patients who did not receive the cytokine (p = 0.013). Despite the early peak in
      CSA in the majority of patients, there was no correlation between the time at
      which CSA was maximum and the return of patients' neutrophils to 500/microliters.
      Recombinant human interleukin 4 (IL-4) increased the number of granulocyte
      macrophage colony-forming unit colonies, principally granulocyte colony-forming
      unit colonies, from normal bone marrow exposed to patients' serum after intensive
      therapy and antibody to GM-CSF reduced colony numbers. The results suggest that
      after intensive therapy granulocyte colony-stimulating factor (G-CSF) as well as
      GM-CSF is released into the serum and, in addition to acting directly with G-CSF,
      IL-4 may stimulate mononuclear cells to produce and/or release G-CSF.

PMID- 1371967
TI  - Influence of combinations of cytokines on proliferation of isolated single cell
      sorted human bone marrow hematopoietic progenitor cells in the absence and
      presence of serum.
AB  - Human mast cell growth factor (MGF, a c-kit ligand) and colony stimulating
      factors (Epo, GM-CSF, G-CSF, IL-3) were assessed in the absence or presence of
      serum for stimulation in semi-solid medium of single CD34 , CD34 HLA-DR+, or CD34
      HLA-DR+CD33- cells sorted per microtiter well. The % of wells containing CFU-GM
      and erythroid containing (BFU-E and CFU-GEMM) colonies increased in proportion to
      the number of cytokines added. In the presence of serum, 1, to 4 cytokine
      combinations resulted in respective increases in cloning efficiencies of 10 to
      21.0, 19.5 to 31.5, 35.8 to 42.9, and 46.3 to 60.0%. MGF had little effect by
      itself, but did act in combination with CSFs to enhance numbers and size of the
      colonies from isolated single cells. High cloning efficiencies were also obtained
      in the absence of serum when multiple cytokines were used. The results
      demonstrate that MGF and CSFs can act directly on the proliferation of single
      hematopoietic progenitor cells in the absence of accessory cells and serum.

PMID- 1371968
TI  - 'boxA'-like sequence between the 16 S/23 S spacer in rRNA operon of mycoplasmas.
AB  - We have found that a boxA-like sequence is conserved in the 16 S and 23 S rRNA
      intergenic spacer regions of mycoplasmas, and that it always locates on loop
      regions of the hypothetical secondary stem-loop structures. A nucleotide sequence
      similar to the '-10' box of prokaryotic promoters was identified at upstream
      sites of the boxA-like sequence in the 16 S/23 S spacer regions. These structures
      may represent an internal promoter between the 16 S and 23 S rRNA genes in
      mycoplasmas.

PMID- 1371969
TI  - Native-type DHP-sensitive calcium channel currents are produced by cloned rat
      aortic smooth muscle and cardiac alpha 1 subunits expressed in Xenopus laevis
      oocytes and are regulated by alpha 2- and beta-subunits.
AB  - Native tissue-like L-type voltage-dependent calcium channels (L-VDCC's) were
      expressed by in vitro transcribed cRNA injection of rat aorta or rabbit cardiac
      alpha 1 subunit into Xenopus laevis oocytes. Co-injection of VSM-alpha 1 with the
      cloned skeletal muscle beta-subunit (SK-beta) of the L-type VDCC significantly
      increased the expressed peak current amplitude without significant changes in
      kinetics. Similar results were obtained by co-injection of cardiac alpha 1 (DSHT
      alpha 1) the cloned skeletal alpha 2-subunit (SK-alpha 2) or with SK-beta. The
      oocytes co-expressing cRNA's retained L-type VDCC pharmacology.

PMID- 1371970
TI  - Mechanism and site of action of a ribosome-inactivating protein type 1 from
      Dianthus barbatus which inactivates Escherichia coli ribosomes.
AB  - A single chain ribosome-inactivating protein with RNA N-glycosidase activity,
      here named Dianthin 29, was isolated from leaves of Dianthus barbatus L.
      Incubation of intact Escherichia coli ribosomes with Dianthin 29 and subsequent
      aniline treatment of the isolated rRNA releases a rRNA fragment of 243
      nucleotides from 23 S rRNA. Nucleotide sequence studies showed that the site of N
      glycosidic bond cleavage is at A-2660 within the universally conserved sequence
      5'-AGUACGAGAGGA-3' near the 3'-end of 23/28 S rRNAs. To our knowledge, Dianthin
      29 is the first ribosome-inactivating protein which is shown to inactivate intact
      prokaryotic ribosomes in the same manner as eukaryotic ribosomes.

PMID- 1371971
TI  - Characterization of Le(x), Le(y) and A Le(y) antigen determinants in KDN
      containing O-linked glycan chains from Pleurodeles waltlii jelly coat eggs.
AB  - Novel acidic oligosaccharides were isolated in large amounts by reductive
      alkaline treatment of the jelly coat of Pleurodeles waltlii (Michah) eggs. The
      oligosaccharides were found to contain the newly described KDN as acidic
      monosaccharide and possess either the Le(x), Le(y) and A Le(y) antigenic
      determinants. Occurrence of Le(x) and Le(y) determinants previously recognized as
      tumor-associated antigen (TAA) demonstrates that mucins of lower animals may
      represent a rich and easily available source for preparing TAA. Moreover, it
      reinforces the hypothesis according to which TAA are evolution markers.

PMID- 1371972
TI  - Synthesis of alpha 1-microglobulin in cultured rat hepatocytes is stimulated by
      interleukin-6, leukemia inhibitory factor, dexamethasone and retinoic acid.
AB  - The secretion of alpha 1-microglobulin by primary cultures of rat hepatocytes was
      found to increase upon the addition of interleukin-6 or leukemia inhibitory
      factor, two mediators of acute phase response. This stimulatory effect was
      further enhanced by dexamethasone. alpha 1-Microglobulin is synthesized as a
      precursor also containing bikunin, and the precursor protein is cleaved shortly
      before secretion. Our results therefore suggest that both alpha 1-microglobulin
      and bikunin are acute phase reactants in rat hepatocytes. Furthermore, we found
      that retinoic acid, previously shown to be involved in the regulation of cell
      differentiation and development, also stimulated alpha 1-microglobulin synthesis.
      Only free, uncomplexed alpha 1-microglobulin (28,000 Da) was detected in the
      hepatocyte media, suggesting that the complex between alpha 1-microglobulin and
      alpha 1-inhibitor 3, found in rat serum, is formed outside the hepatocyte.

PMID- 1371973
TI  - The first epidermal growth factor domain of human coagulation factor VII is
      essential for binding with tissue factor.
AB  - The intrinsic pathway of coagulation is initiated when zymogen factor VII binds
      to its cell surface receptor tissue factor to form a catalytic binary complex.
      Both the activation of factor VIIa and the expression of serine protease activity
      of factor VIIa are dependent on factor VII binding to tissue factor lipoprotein.
      To better understand the molecular basis of these rate-limiting events, the
      interaction of zymogen factor VII and tissue factor was investigated using as
      probes both a murine monoclonal antibody and a monospecific rabbit antiserum to
      human factor VII. To measure factor VIIa functional activity, a two-stage
      chromogenic assay was used; an assay which measures the factor Xa generated by
      the activation of factor VII to factor VIIa. Purified immunoglobulin from murine
      monoclonal antibody 231-7, which was shown to be reactive with amino acid
      residues 51-88 of the first epidermal growth factor-like (EGF) domain of human
      factor VII, inhibited the activation of factor VII to factor VIIa in a dose
      dependent manner. The mechanism of this inhibition was demonstrated using a novel
      solid-phase ELISA which quantitatively measured the binding of purified factor
      VII zymogen to tissue factor adsorbed onto microtiter wells. Thus, the binding of
      factor VII zymogen to immobilized tissue factor was inhibited by antibody 231-7,
      again in a dose-dependent manner. Similar results were obtained using a
      monospecific rabbit antiserum to human factor VII which also reacted with the
      beta-galactosidase fusion proteins containing amino acid residues 51-88 (exon 4)
      of human factor VII. We conclude therefore that the exon 4-encoded amino acids of
      the first EGF domain of human factor VII constitute an essential domain
      participating in the binding of factor VII to tissue factor.

PMID- 1371974
TI  - cDNA clones encoding leucine-zipper proteins which interact with G-CSF gene
      promoter element 1-binding protein.
AB  - The gene expression of granulocyte colony-stimulating factor (G-CSF) is induced
      by lipopolysaccharide (LPS). GPE1, a cis-controlling element of the G-CSF gene,
      functions as an LPS-responsive element. GPE1-binding protein (GPE1-BP), a leucine
      zipper protein, did not independently activate G-CSF gene expression. Protein
      blot analysis with biotinylated GPE1-BP revealed that there were nuclear proteins
      that interact specifically with GPE1-BP. Three leucine-zipper proteins were
      isolated from mouse cDNA expression libraries by this method: NF-IL6, ATF4, and a
      novel ATF4-related ATFx. The interactions of these proteins with GPE1-BP may play
      key roles in G-CSF gene expression.

PMID- 1371976
TI  - Human centrosomal epitope is shared specifically with human lactate dehydrogenase
      B isozyme.
AB  - A rabbit serum (0013) used to identify pericentriolar proteins from isolated
      centrosomes (Gosti-Testu, F., Marty, M.C., Berges, J., Maunoury, R. and Bornens,
      M. (1986) EMBO J. 5, 2545-2550) was shown also to react through the same epitope
      with several non-centrosomal proteins including a major 36 kDa cytosolic antigen.
      This protein was identified to be human lactate dehydrogenase and the co
      distribution of 0013 epitope on the centrosomal protein and on lactate
      dehydrogenase (LDH) was shown to be specific for human cells (Gosti, F., Marty,
      M.C., Courvalin, J.C., Maunoury, R. and Bornens, M. (1987) Proc. Natl. Acad. Sci.
      USA 84, 1000-1004). Human hepatic cells constitute, so far, the only exception to
      this co-distribution rule. By using this cell type which expresses only the LDH
      A4 isozyme, we demonstrate that 0013 epitope is specific for the human LDH-B
      subunit, making serum 0013 the strongest anti-LDH-B available so far. The
      evolutionary and physiological significance of this situation is discussed.

PMID- 1371975
TI  - Interaction of cholesterol-conjugated alkylating oligonucleotide derivatives with
      cellular biopolymers.
AB  - Interactions of oligonucleotide derivatives with mammalian cells and cellular
      biopolymers have been investigated. The derivatives were oligonucleotides bearing
      an alkylating 2-chloroethylamino group at the 3'-end and a cholesterol residue at
      the 5'-terminal phosphate. These compounds are readily taken up by cells and
      react with cellular DNA, RNA and some proteins which may play a role in delivery
      of the compounds into cells.

PMID- 1371977
TI  - Immunological modulation of lymphocyte subpopulation in cervical cancer tissue by
      sizofiran and OK-432.
AB  - The intimate correlation between marked lymphocyte infiltration in the cancer
      tissue and the superior clinical prognosis has been reported in human cancers.
      Sizofiran (SPG), a polysaccharide consisting of beta-1,3-D-glucopyranosyl linkage
      with beta-1,6-D-glucopyranosyl branches, or OK-432, a heat- and penicillin
      treated, lyophilized preparation of the Su strain of Streptococcus pyogenes of
      human origin, was administered intratumorally to nine patients with advanced
      uterine cervical carcinoma before radical hysterectomy to assess their
      immunological modulating properties to tumor-infiltrating lymphocyte
      subpopulations immunohistochemically. The degree of infiltration of CD3- and CD5
      positive cells increased moderately or markedly in the stroma surrounding the
      lesion in both SPG group and OK-432 group, as well as that of CD4- and CD8
      positive cells, from that before administration. The density of infiltration of
      CD3-positive, CD4-positive, and CD8-positive cells in the lesion increased
      slightly or moderately in both groups after administration. As for CD16-positive
      cell infiltration, both SPG and OK-432 increased its degree in the stroma lining
      the lesion while SPG alone augmented its degree in the lesion. This augmentation
      of lymphocyte infiltration in situ induced by intratumoral administration of SPG
      and OK-432 is expected to lead to a favorable prognosis of patients with cervical
      cancer.

PMID- 1371978
TI  - Preliminary results of concurrent radiotherapy and chemotherapy with cis
      platinum, vincristine, and bleomycin in bulky, advanced cervical carcinoma: a
      pilot study.
AB  - Twenty-four patients with bulky (greater than 4 cm), advanced (stages IIB-IVA)
      carcinoma of the uterine cervix were prospectively treated with a concurrent
      combination of radiotherapy (RT) and chemotherapy (CT). RT consisted of 4400 cGy
      (22 fractions) to the whole pelvis and a 1400-cGy boost to the parametrium. This
      was followed by two to three intracavitary brachytherapy courses. CT consisted of
      one to four course (median, three) of cisplatin (50 mg/m2) on Day 1, vincristine
      (1 mg/m2) on Day 2, and bleomycin (25 mg/m2) on Days 2-4. CT was started on the
      first day of external radiation and the scheduled course interval was 21 days.
      Among the 20 evaluable patients who completed at least one course of chemotherapy
      and a full course of radiation, 13 (65%) achieved complete response and 5 (25%)
      had partial response. Fatal complication occurred in 1 patient with stationary
      disease who died of septic shock due to ruptured pyometra. The other patient with
      primary stage IVA disease had progressive disease with ascites appearance after
      two courses of CT and later expired. Transient drug fever occurred in 19 (40.4%)
      of the 47 bleomycin-containing CT cycles. Grade 2 or 3 hematological toxicities
      occurred in 16 (30.2%) of a total of 53 CT cycles. Treatment delays of 1 to 7
      days occurred in 15 (28.3%) CT cycles. Except for the case of septic shock, all
      of the other toxicities were generally tolerable and reversible. From this
      preliminary result we concluded that this particular combination of RT and CT in
      bulky, advanced cervical carcinoma is effective in enhancing local pelvic tumor
      control and well tolerated if strict selection of accrued patients is applied.
      Further investigation to assess its impact on long-term survival is in progress.

PMID- 1371979
TI  - Use of designer recombinant mitochondrial antigens in the diagnosis of primary
      biliary cirrhosis.
AB  - The appearance of autoantibodies against mitochondria in patients with primary
      biliary cirrhosis has been known for more than 25 yr. In the past, based on the
      biochemical complexity of the mitochondrion and the use of crude extracts for
      immunodiagnosis, a degree of nonspecificity in assaying for antibodies to
      mitochondria has been present. This problem has been largely circumvented by the
      cloning of the mitochondrial antigens and the identification of the E2 subunits
      of the pyruvate dehydrogenase complex and the branched chain 2-oxo-acid
      dehydrogenase complex as the major and immunodominant autoantigens of primary
      biliary cirrhosis. More than 90% of patients with primary biliary cirrhosis have
      been shown to react with one or both of these enzymes using either recombinant
      antigen or purified native protein. Approximately 10% of patients recognize only
      E2 subunits of branched chain 2-oxo-acid dehydrogenase complex and not pyruvate
      dehydrogenase complex. Such patients would be missed by diagnostic assay that has
      a low sensitivity to antibodies against E2 subunits of branched chain 2-oxo-acid
      dehydrogenase complex. The use of recombinant and biochemically pure antigens has
      permitted structural and conformational analysis of epitope mapping. We have
      taken advantage of the antigenic mapping studies of both primary biliary
      cirrhosis and branched chain 2-oxo-acid dehydrogenase complex E2 subunits and
      designed a molecule that expresses the immunodominant epitopes of both. Using
      this dual-headed molecule that coexpresses the epitope of two different antigens,
      we report herein a sensitive and reproducible assay for antibodies to
      mitochondria in patients with primary biliary cirrhosis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1371980
TI  - Polyunsaturated lecithin prevents acetaldehyde-mediated hepatic collagen
      accumulation by stimulating collagenase activity in cultured lipocytes.
AB  - We recently found that polyunsaturated lecithin prevents ethanol from causing
      cirrhosis in the baboon. Because transformation of lipocytes to transitional
      cells plays a key role in hepatic fibrogenesis in vivo, and because this process
      in alcohol-fed baboons was found to be attenuated by polyunsaturated lecithin, we
      focused on lipocytes to study the mechanism of the protective effect. Rat
      lipocytes cultured on plastic undergo spontaneous activation, accompanied by
      expression of alpha-smooth muscle actin isoform and production of substantial
      amounts of type I collagen. The latter was further increased on incubation with
      acetaldehyde. This in vitro model was used here to study how acetaldehyde
      mediated collagen production and accumulation can be turned off. Addition of
      polyunsaturated lecithin (10 mumols/L) was found to prevent the acetaldehyde
      induced increase in collagen accumulation by 83% (p less than 0.001). By
      contrast, a saturated phospholipid (10 mumols/L dilauroyl phosphatidylcholine), a
      monounsaturated one (10 mumols/L linoleoyl-palmitoyl phosphatidylcholine) or
      linoleic acid (20 mumols/L bound to albumin) had no such effect. Incorporation of
      [3H]proline into collagen and the expression of alpha-1 (I) procollagen mRNA were
      increased by acetaldehyde; the latter was not significantly affected by
      polyunsaturated lecithin. Polyunsaturated lecithin increased lipocyte collagenase
      activity by 100% (p less than 0.001), whereas dilauroyl phosphatidylcholine,
      linoleoyl-palmitoyl phosphatidylcholine and linoleic acid had no such action. We
      concluded that (a) polyunsaturated lecithin selectively prevents the acetaldehyde
      induced increase in collagen accumulation in lipocyte cultures, whereas other
      phospholipids or linoleate have no such effect; and (b) polyunsaturated lecithin
      does not modify the acetaldehyde-mediated increase in alpha-1 (I) procollagen
      mRNA, but it increases collagenase activity, suggesting that the protective
      effect exerted by polyunsaturated lecithin against alcohol induced fibrosis in
      vivo is due at least in part to stimulation of collagenase activity, which may
      prevent excess collagen accumulation by offsetting increased collagen production.

PMID- 1371981
TI  - Improved serodiagnosis of non-A, non-B hepatitis by an assay detecting antibody
      to hepatitis C virus core antigen.
AB  - We examined sequential serum samples from 12 patients with well-characterized
      posttransfusion non-A, non-B hepatitis who had an acute, resolving self-limited
      type of clinical course for the presence of antibody to the hepatitis C virus
      nucleocapsid (core) protein (p22) expressed by a recombinant baculovirus. These
      sera were simultaneously examined for antibody to the hepatitis C virus
      nonstructural protein (C100-3) that is presently used for blood screening
      worldwide. In three patients, both anti-p22 and anti-C100-3 antibodies were
      detected, but anti-p22 was detected much earlier. In four patients, only anti-p22
      was detected. Two other patients were considered to be hepatitis C virus carriers
      who had been already infected with hepatitis C virus. In one patient, only anti
      C100-3 was detected, and it was transient. In two patients, neither antibody was
      detected. Anti-p22 was detected in at least one of eight samples of transfused
      blood. Of the nine samples of donated blood that were positive for anti-p22, only
      four were positive for anti-C100-3. This new assay detecting the antibody to the
      p22 protein is thus useful for the serodiagnosis of non-A, non-B hepatitis in the
      acute phase and for blood screening.

PMID- 1371982
TI  - Differences in the abundance of variably spliced transcripts for the second
      asialoglycoprotein receptor polypeptide, H2, in normal and transformed human
      liver.
AB  - The human hepatic asialoglycoprotein receptor comprises two homologous
      polypeptides designated H1 and H2. Two distinct complementary DNA clones encoding
      these receptor subunits have been previously isolated from the human
      hepatoblastoma cell line HepG2. We discovered that multiple variants of H2
      transcripts exist both in HepG2 cells and in the normal human liver that, at
      least in part, appear to be the result of alternative splicing events. We have
      found that (a) the complementary DNA clone for H2 previously isolated from HepG2
      cells, characterized by a 57-nucleotide insertion within the 5' end of the
      complementary DNA that is absent from H1, represented only one third of H2
      related sequences in an unamplified normal human liver complementary DNA library
      and less than 10% of H2 clones in HepG2 cells; (b) the predominant message for H2
      expressed in the liver and HepG2 cells, designated L-H2, appeared to represent
      the fully processed product of the gene encoding both L-H2 and H2; and (c) a
      variant H2 transcript existed in HepG2 cells, designated H2', that contained a
      novel, 5' 88-bp nucleotide insertion. Poly(A+) RNA analysis of the normal liver
      and HepG2 cells by complementary RNA hybridization and ribonuclease protection
      corroborated the observations made during the screening of complementary DNA
      libraries regarding the abundance of the various messages. A striking incongruity
      was found between the levels of messenger RNA containing the H2-specific 57
      nucleotide sequence and the levels of polypeptide expressed in the liver and
      HepG2 cells as recognized by antiserum specifically raised against this sequence.

PMID- 1371984
TI  - Distribution of Leu-7 antigen (HNK-1) in thyroid tumors: its usefulness as a
      diagnostic marker for follicular and papillary carcinomas.
AB  - The reactivity of the anti-Leu-7 monoclonal antibody was tested in 39 neoplastic
      and nonneoplastic thyroid tissue specimens. These included eight colloid goiters,
      14 follicular adenomas, nine papillary carcinomas, five follicular carcinomas,
      two medullary carcinomas, and one metastatic follicular carcinoma in bone. We
      observed strong cytoplasmic and/or cell membrane positivity in all follicular and
      papillary carcinomas, in both primary and metastatic tumors. However, the
      medullary thyroid carcinomas tested were negative. We also observed weak and only
      occasional staining with anti-Leu-7 antibody in colloid goiter and follicular
      adenomas. The staining in the benign thyroid lesions was usually focal, less than
      10% of the cells; however, in cases of follicular and papillary carcinomas, both
      in primary and metastatic tumors, the staining was diffuse and strong. Some of
      the colloid material in colloid goiters and follicular adenomas showed faint
      homogenous staining with anti-Leu-7 antibody. Our findings suggest that anti-Leu
      7 monoclonal antibody is a marker that may facilitate the differentiation between
      benign and malignant thyroid lesions, with the exception of medullary carcinoma.
      In addition, caution should be taken when using this antibody to diagnose
      metastatic lesions, as other metastatic carcinomas have also been reported to be
      positive. This antibody should be used in conjunction with a panel of antisera to
      complement a morphologic diagnosis.

PMID- 1371983
TI  - Immunohistochemical study of extracellular matrix in acute galactosamine
      hepatitis in rats.
AB  - A single injection of D-galactosamine hydrochloride induces acute self-limiting
      liver disease in rats that morphologically resembles drug-induced hepatitis in
      human beings. In this immunohistochemical study we examined the localization and
      expression of the hepatic extracellular matrix components fibronectin, laminin,
      collagen type I, collagen type III and collagen type IV and of the cell surface
      receptors (integrins) for fibronectin and laminin. Sections of liver tissue
      obtained at intervals of 6, 12, 18, 24, 30, 36, 48 and 72 hr and 7 and 21 days
      after galactosamine administration were immunostained with a panel of polyclonal
      monospecific antibodies and studied independently by two of us. Fibronectin was
      the first extracellular matrix component found to be increased, 12 hr after
      galactosamine injection, followed by collagen type III, and, in a later phase,
      collagen type IV, type I and laminin. Increased deposition of extracellular
      matrix was found in areas with liver cell necrosis and along sinusoids.
      Extracellular matrix immunoreactivity reached a maximum at 36 to 48 hr and
      decreased thereafter to preinjury levels 3 wk after galactosamine. Immunostaining
      for the fibronectin and laminin receptors revealed tissue localization identical
      to that of their ligands. However, the intensity of staining was opposite of that
      for the extracellular matrix, with a decrease of immunoreactivity after 24 to 48
      hr. The observed sequence of changes in hepatic extracellular matrix proteins
      after galactosamine injection resembles the repair reaction in other tissues and
      may reflect the particular function that each carries out during the process of
      liver healing after toxic injury.

PMID- 1371985
TI  - Anti-CD34 immunoperoxidase staining in paraffin sections of acute leukemia:
      comparison with flow cytometric immunophenotyping.
AB  - Anti-CD34 is a monoclonal antibody that reacts with bone marrow progenitor cells
      and leukemic blasts, and is expressed on 30% to 50% of all acute leukemias.
      Detection of CD34 has previously been restricted to flow cytometric studies. To
      expand the utility of CD34, we immunostained 46 paraffin-embedded bone marrow
      specimens with acute leukemia; results were compared with flow cytometric
      studies. CD34 reactivity was also evaluated in nine chronic leukemia cases, 27
      malignant lymphoma cases (Hodgkin's disease and non-Hodgkin's lymphoma), six
      normal bone marrow specimens, and three benign, hyperplastic lymph node
      specimens. All cases that were CD34 positive by flow cytometry (11 of 19 B-cell
      precursor acute lymphoblastic leukemia cases, one of six T-cell acute
      lymphoblastic leukemia cases, and seven of 21 acute myeloblastic leukemia cases)
      were also CD34 positive in paraffin sections. Both cell membrane and cytoplasmic
      staining was seen. The positivity percentage and fluorescence intensity by flow
      cytometry correlated with the estimated number of stained cells and the intensity
      of immunoperoxidase staining in 18 of 19 CD34-positive cases. The remaining bone
      marrow and lymph node cases studied were CD34 negative; prominent endothelial
      cell staining, however, was noted. This is the first report of anti-CD34 staining
      of acute leukemia in paraffin-embedded sections. In contrast to other monoclonal
      antibodies reactive in bone marrow paraffin sections with leukemia, anti-CD34
      immunoperoxidase staining is limited to leukemic blasts and may provide useful
      diagnostic information when flow cytometric studies are not available.

PMID- 1371986
TI  - Palliation in the age of chronic disease.

PMID- 1371987
TI  - Molecular mechanisms of trenimon-induced cytotoxicity in resistant L5178Y/HBM10
      cells.
AB  - L5178Y/HBM10 lymphoblasts, resistant to a model quinone antitumor agent,
      hydrolyzed benzoquinone mustard, were approximately 2-fold more sensitive to
      trenimon (2,3,5-tris-ethyleneimino-1,4-benzoquinone) compared to parental cells
      (L5178Y). The L5178Y/HBM10 cells are reported to have a 24-fold increased level
      of DT-diaphorase activity over the parental cells. Inhibition of DT-diaphorase by
      dicoumarol markedly inhibited the cytotoxic activity of trenimon to the resistant
      L5178Y/HBM10 cells. Spectrophotometric analysis of the reduction of the quinone,
      trenimon, to its hydroquinone form was shown to occur approximately 25 times more
      rapidly in the L5178Y/HBM10 cells relative to the parental cells and was
      inhibited by discoumarol. Trenimon also induced continuous cyanide-resistant
      respiration in the L5178Y cells, but not in the resistant L5178Y/HBM10 cells.
      This suggested a one-electron reduction of trenimon to a semiquinone free radical
      which could then redox cycle with oxygen in the L5178Y cells. However, in the
      presence of dicoumarol the resistant L5178Y/HBM10 cells induced similar oxygen
      activation to the parental cells. Dicoumarol had no effect on trenimon-induced
      cyanide resistant respiration in the parental cells. These findings suggest that
      the two-electron reduction of trenimon to its hydroquinone derivative plays a
      major role in the cytotoxic activity of trenimon.

PMID- 1371988
TI  - Postirradiation treatment with granulocyte colony-stimulating factor and
      preirradiation WR-2721 administration synergize to enhance hemopoietic
      reconstitution and increase survival.
AB  - These studies tested whether WR-2721 could be used to protect hemopoietic stem
      cells, which after irradiation could be stimulated by granulocyte colony
      stimulating factor (G-CSF) to proliferate and reconstitute the hemopoietic
      system. Female C3H/HeN mice were administered WR-2721 (4 mg/mouse, i.p.) 30 min
      before 60Co irradiation and G-CSF (2.5 micrograms/mouse/day, s.c.) from days 1-16
      after irradiation. In survival studies, saline, G-CSF, WR-2721, and WR-2721 + G
      CSF treatments resulted in LD50/30 values of 7.85 Gy, 8.30 Gy, 11.30 Gy, and
      12.85 Gy, respectively. At these LD50/30 values, the dose reduction factor (DRF)
      of 1.64 obtained in combination-treated mice was more than additive between the
      DRF's of G-CSF-treated mice (1.06) and WR-2721-treated mice (1.44). Bone marrow
      and splenic multipotent hemopoietic stem cell (CFU-s) and granulocyte-macrophage
      progenitor cell (GM-CFC) recoveries were also accelerated most in mice treated
      with WR-2721 + G-CSF. In addition, mice treated with WR-2721 + G-CSF exhibited
      the most accelerated peripheral blood white cell, platelet, and red cell
      recoveries. These studies (a) demonstrate that therapeutically administered G-CSF
      accelerates hemopoietic reconstitution from WR-2721-protected stem and progenitor
      cells, increasing the survival-enhancing effects of WR-2721 and (b) suggest that
      classic radioprotectants and recombinant hemopoietic growth factors can be used
      in combination to reduce risks associated with myelosuppression induced by
      radiation or radiomimetic drugs.

PMID- 1371989
TI  - Expression of 85-kDa protein of adriamycin-resistant tumor cells during
      hematopoietic differentiation of THP-1 and HEL cells.
AB  - An 85-kDa protein was identified in adriamycin-resistant tumor cells recognized
      by monoclonal antibody MRK-20. Recently, the monoclonal antibody MRK-20 was found
      to be reactive to human peripheral mononuclear cells. In order to investigate the
      molecular function of the 85-kDa protein, we carried out flow cytometric analysis
      of the expression of the 85-kDa protein during monocytic differentiation of the
      hematopoietic cells. Human myelomonocytic leukemia THP-1 cells were induced to
      differentiate into macrophage-like cells by treatment with 12-O
      tetradecanoylphorbol-13-acetate (TPA). A maximum of 55% of the cells expressed
      the 85-kDa protein along with the CD-14 antigen, which is a surface marker of
      monocytes and macrophages. The kinetic analysis revealed that the 85-kDa protein
      appeared prior to the expression of the CD-14 antigen. The 85-kDa protein was
      also coexpressed with CD-14 in THP-1 cells that were induced to differentiate by
      recombinant tumor necrosis factor-alpha, which is one of the physiological
      inducers of monocytic differentiation. In human erythroleukemia, HEL cells, the
      85-kDa protein was constitutively coexpressed with CD-14. The expression of both
      the 85-kDa protein and CD-14 was drastically reduced during the megakaryocytic
      differentiation of the HEL cells with TPA. These results suggest that the 85-kDa
      protein could be expressed on monocytic cells as well as CD-14 and that the
      expression of the 85-kDa protein might be regulated at an earlier stage of
      monocytic differentiation of hematopoietic cells than the expression of CD-14.

PMID- 1371990
TI  - Detection of the ligand activity of the c-erbB-2 protein in calf serum.
AB  - We established NIH3T3 derivatives in which wild-type c-erbB-2 or activated c-erbB
      2 having a point mutation in the sequence coding for the transmembrane domain was
      expressed. These cell lines were termed RC and A4, respectively. A4 cells but not
      RC or NIH3T3 cells grew even in the presence of a low concentration (0.05%) of
      calf serum (CS), although the rate of their proliferation was low. In media
      containing 0.1% CS, both A4 cells and RC cells but not NIH3T3 cells could
      proliferate. Furthermore, RC cells induced foci formation when cultured in media
      containing 0.5% and 5% CS, while growth of the parental NIH3T3 cells was contact
      inhibited under these conditions. These data suggest the presence of a factor(s)
      which activates protein-tyrosine kinase activity of the c-erbB-2 protein. In
      fact, the c-erbB-2 protein prepared from RC cells showed CS-dependent protein
      tyrosine kinase activity when assayed in membrane fractions.

PMID- 1371992
TI  - The interferon system. A bird's eye view of its biochemistry.

PMID- 1371991
TI  - Okadaic acid is a potent angiogenesis inducer.
AB  - Okadaic acid, which is a non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type
      tumor promoter and an inhibitor of protein phosphatases 1 and 2A, induced
      angiogenesis in the chorioallantoic membrane of the chick embryo. Its potent
      angiogenic activity was dose-dependent. The minimum effective dose was 5 fmol/egg
      and the effective dose for 50% induction was 90 fmol/egg. These results indicated
      that okadaic acid exhibits angiogenic activity one order of magnitude stronger
      than that of TPA (reported previously). Moreover, the time-course of angiogenesis
      induction by okadaic acid was much slower than that by TPA. The difference is
      consistent with the time-courses of other biochemical and biological activities
      and also various gene expressions induced by okadaic acid and TPA, indicating
      that the difference in the time-course is associated with their mechanisms of
      action. We conclude that okadaic acid induces angiogenesis through a different
      pathway than does TPA, indicating the existence of a new mechanism of
      angiogenesis induction.

PMID- 1371993
TI  - Differential expression of three C/EBP isoforms in multiple tissues during the
      acute phase response.
AB  - Eucaryotic organisms possess natural defense processes triggered by stress
      factors such as injury, infection, and inflammation. The acute phase response is
      an early defense mechanism during which striking changes in protein synthesis
      occur in the liver and other tissues. The altered expression of many acute phase
      protein genes is at the transcriptional level. Some of these genes have DNA
      binding sites for the CCAAT/enhancer binding protein (C/EBP) family of
      transcription factors. We report here that in vivo expression of three isoforms
      of C/EBP is dramatically changed during the acute phase response. The steady
      state mRNA levels of C/EBP alpha decreased significantly in the liver, lung, and
      fat tissues of lipopolysaccharide (LPS)-treated mice; moreover, nuclear run-off
      transcription assays indicated a decrease in the rate of C/EBP alpha gene
      transcription in isolated liver nuclei. The steady-state levels of C/EBP beta and
      a new isoform, C/EBP delta, were dramatically increased in many tissues within 4
      h following LPS treatment. The rates of transcription of these two genes were
      only minimally altered in liver but significantly increased in kidney nuclei
      isolated from stimulated animals. Thus, the C/EBP isoforms exhibit differential
      mechanisms in their responses to LPS in various tissues and are likely to play an
      important role in mediating the transcriptional activation of genes involved in
      the acute phase response.

PMID- 1371994
TI  - Signal transduction by tumor necrosis factor alpha is mediated through a guanine
      nucleotide-binding protein in osteoblast-like cell line, MC3T3-E1.
AB  - Transmembrane signalling mechanisms of tumor necrosis factor alpha (TNF alpha)
      were examined with special reference to the involvement of G-protein, in intact
      and permeabilized murine osteoblast-like cells. TNF alpha stimulated the release
      of 3H radioactivity from intact cells labeled with [3H]arachidonic acid within 10
      min in a dose dependent manner and the production of lyso forms of phospholipids,
      an event presumably mediated through the activation of phospholipase A2.
      Production of cAMP and inositol 1,4,5-trisphosphate was not affected by TNF
      alpha. Pretreatment of the cells with pertussis toxin inhibited the liberation of
      [3H]arachidonate. GTP gamma S (guanosine 5'-3-O-(thio)triphosphate) reduced the
      binding affinity of [125I]TNF alpha to beta-escin-permeabilized cells. The
      addition of TNF alpha together with an unhydrolyzable analog of GTP, GTP gamma S,
      to the beta-escin-permeabilized cells prelabeled with [3H]arachidonic acid led to
      a release of the 3H radioactivity. The production of prostaglandin E2 (PGE2) was
      markedly stimulated by TNF alpha in a dose over 100 ng/ml, with a latent time of
      about 3 h, and the stimulation was abolished by pretreatment with pertussis
      toxin. The time and dose requirements for this process differed from those for
      the possible activation of phospholipase A2, thereby indicating that other
      process(es) in addition to the activation of phospholipase A2 may be responsible
      for the enhanced production of PGE2. The activity of cyclooxygenase (i.e. the
      combined activities of prostaglandin endoperoxide syntase and PGH2-PGE2
      isomerase) was stimulated by TNF alpha with much the same time and dose
      requirements as for the production of PGE2, and the activation was found to be
      due to the increased amount of the enzyme, as assessed by a Western blot analysis
      with anti-cyclooxygenase antibody. This process was also sensitive to pertussis
      toxin. Therefore, receptors for TNF alpha in MC3T3-E1 cells apparently couple to
      G-protein sensitive to pertussis toxin and the coupling regulates the activations
      of phospholipase A2 and the de novo synthesis of cyclooxygenase.

PMID- 1371995
TI  - Immunochemical detection of advanced glycosylation end products in vivo.
AB  - Reducing sugars react with protein amino groups to form a diverse group of
      protein-bound moieties with fluorescent and cross-linking properties. These
      compounds, called advanced glycosylation end products (AGEs), have been
      implicated in the structural and functional alterations of proteins that occur
      during aging and long-term diabetes. Although several AGEs have been identified
      on the basis of de novo synthesis and tissue isolation procedures, the
      measurement of AGE compounds in vivo has remained difficult. As an approach to
      the study of AGE formation in vivo, we prepared polyclonal antiserum to an AGE
      epitope(s) which forms in vitro after incubation of glucose with ribonuclease
      (RNase). This antiserum proved suitable for the detection of AGEs which form in
      vivo. Both diabetic tissue and serum known to contain elevated levels of AGEs
      readily competed for antibody binding. Cross-reactivity studies revealed the
      presence of a common AGE epitope(s) which forms after the incubation of diverse
      proteins with glucose. Cross-reactive epitopes also formed with glucose 6
      phosphate or fructose. These data suggest that tissue AGEs which form in vivo
      appear to contain a common immunological epitope which cross-reacts with AGEs
      prepared in vitro, supporting the concept that immunologically similar AGE
      structures form from the incubation of sugars with different proteins (Horiuchi,
      S., Araki, N., and Morino, Y. (1991) J. Biol. Chem. 266, 7329-7332). None of the
      known AGEs, such as 4-furanyl-2-furoyl-1H-imidazole, 1-alkyl-2-formyl-3,4
      diglycosylpyrrole, pyrraline, carboxymethyllysine, or pentosidine, were found to
      compete for binding to anti-AGE antibody. These data further suggest that the
      dominant AGE epitope which forms from the reaction of glucose with proteins under
      native conditions is immunologically distinct from the structurally defined AGEs
      described to date.

PMID- 1371996
TI  - Protein kinase C and calmodulin kinase are required for endothelin-stimulated
      atrial natriuretic factor secretion from primary atrial myocytes.
AB  - Endothelin (ET), a potent stimulator of atrial natriuretic factor (ANF) secretion
      in atrial myocyte cultures, has been hypothesized to act via the stimulation of
      protein kinase C (PKC). This study was carried out in order to determine if ET
      activates PKC in atrial cultures and whether this activation fully accounts for
      the effects of ET on ANF secretion. By monitoring the phosphorylation of p80 upon
      exposure to phorbol ester or ET, it was shown that ET activated PKC in atrial
      cultures, but to a lesser extent than phorbol ester. In contrast, ET stimulated
      ANF secretion to a level five times greater than phorbol ester, indicating that
      PKC activation alone does not fully account for the effects of ET on ANF
      secretion. Down-regulation of PKC or exposure to the PKC inhibitor 1-(5
      isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) resulted in a 50%
      decrease in ET-stimulated ANF secretion. Interestingly, increasing calcium influx
      with BAY K 8644 stimulated ANF secretion but did not effect the phosphorylation
      of p80, indicating a PKC-independent pathway of ANF secretion. Similarly, a
      component of ET-stimulated secretion that required calcium influx was independent
      of PKC activation but was sensitive to the Ca2+/calmodulin kinase (CaMK)
      inhibitor KN-62. Complete inhibition of ET-mediated ANF secretion was obtained
      only in the presence of both H7 and KN-62. These results demonstrate that ET
      activates PKC in atrial myocyte cultures and that the full effects of ET on ANF
      secretion require both PKC and Ca2+/calmodulin kinase activities.

PMID- 1371997
TI  - Derivation and characterization of glycoinositol-phospholipid anchor-defective
      human K562 cell clones.
AB  - To aid in studies of human glycoinositol-phospholipid (GPI) anchor pathway
      biochemistry in normal and affected paroxysmal nocturnal hemoglobinuria cells,
      GPI anchor-defective human K562 cell lines were derived by negative fluorescent
      sorting of anti-decay-accelerating factor (DAF) monoclonal antibody-stained cells
      either following or in the absence of ethylmethylsulfonate pretreatment. The
      resulting cloned cells showed deficiencies of both DAF and GPI-anchored CD59,
      some (designated group A) exhibiting total absence and some (designated group B)
      exhibiting approximately 10% levels of surface expression of the two proteins. In
      heterologous cell fusions, group A clones complemented defective Thy-1 expression
      by class A, B, C, E, and I Thy-1-negative lymphoma lines, but not H or D lines,
      the latter of which is defective in the Thy-1 structural gene. In contrast, group
      B clones complemented all previously described GPI anchor pathway-defective
      lymphoma classes. Immunoradiomatic assays of cells and supernatants and 35S
      biosynthetic labeling showed that group A cells degraded DAF protein while group
      B cells secreted it but failed to attach a GPI anchor structure. [3H]Man labeling
      of intact cells and UDP-[3H]GlcNAc and GDP-[3H]Man labeling of broken cell
      preparations demonstrated that group A cells failed to synthesize GlcNAc- and
      GlcN-PI (GPI-A and -B) as well as more polar mannolipids, whereas group B cells
      showed accumulation of GlcNAc-PI with approximately 10-fold diminished levels of
      GlcN-PI and more polar mannolipids. The failed assembly of GlcNAc-PI in group A
      cells and the reduced conversion of this intermediate to GlcN-PI in group B cells
      indicates that the former harbors a defect in UDP-GlcNAc transferase or in
      assembly of its PI acceptor, while the latter harbors a defect in GlcN-PI
      deacetylase activity.

PMID- 1371998
TI  - Developmental variation of glycosylphosphatidylinositol membrane anchors in
      Trypanosoma brucei. In vitro biosynthesis of intermediates in the construction of
      the GPI anchor of the major procyclic surface glycoprotein.
AB  - The African trypanosome, Trypanosoma brucei, expresses two abundant stage
      specific glycosylphosphatidylinositol (GPI)-anchored glycoproteins, the procyclic
      acidic repetitive protein (PARP or procyclin) in the procyclic form, and the
      variant surface glycoprotein (VSG) in the mammalian bloodstream form. The GPI
      anchor of VSG can be readily cleaved by phosphatidylinositol (PI)-specific
      phospholipase C (PI-PLC), whereas that of PARP cannot, due to the presence of a
      fatty acid esterified to the inositol. In the bloodstream form trypanosome, a
      number of GPIs which are structurally related to the VSG GPI anchor have been
      identified. In addition, several structurally homologous GPIs have been
      described, both in vivo and in vitro, that contain acyl-inositol. In vivo the
      procyclic stage trypanosome synthesizes a GPI that is structurally homologous to
      the PARP GPI anchor, i.e. contains acyl-inositol. No PI-PLC-sensitive GPIs have
      been detected in the procyclic form. Using a membrane preparation from procyclic
      trypanosomes which is capable of synthesizing GPI lipids upon the addition of
      nucleotide sugars we find that intermediate glycolipids are predominantly of the
      acyl-inositol type, and the mature ethanolamine-phosphate-containing precursors
      are exclusively acylated. We suggest that the differences between the bloodstream
      and procyclic form GPI biosynthetic intermediates can be accounted for by the
      developmental regulation of an inositol acylhydrolase, which is active only in
      the bloodstream form, and a glyceride fatty acid remodeling system, which is only
      partially functional in the procyclic form.

PMID- 1371999
TI  - cDNA for the carboxyl-terminal region of a rat intestinal mucin-like peptide.
AB  - When subjected to thiol reduction, purified intestinal mucins have been shown to
      undergo a decrease in molecular mass and to liberate a 118-kDa glycopeptide
      (Roberton, A. M., Mantle, M., Fahim, R. E. F., Specian, R., Bennick, A.,
      Kawagishi, S., Sherman, P., and Forstner, J. F. (1989) Biochem. J. 261, 637-647).
      The latter has been called a putative "link" component because it is assumed to
      be important for disulfide bond-mediated mucin polymerization. Controversy exists
      as to whether the putative link is an integral mucin component or a separate
      mucin-associated glycopeptide. In the present study both NH2-terminal and
      internal amino acid sequences of the 118-kDa glycopeptide of rat intestinal mucin
      were used to generate opposing oligonucleotide primers for polymerase chain
      reaction. A specific 1.2-kilobase (kb) product was obtained, from which a 0.5-kb
      HindIII fragment was used as a probe to screen a lambda ZAP II cDNA library of
      rat intestine. A 2.6-kb cDNA (designated MLP 2677) was sequenced and revealed an
      open reading frame of 2.5 kb encoding 837 amino acids. The deduced amino acid
      sequence showed that the putative link peptide is equivalent to the carboxyl
      terminal 689 amino acids of a larger peptide. Northern blots revealed a mRNA size
      of approximately 9 kb. Computer searches revealed no sequence homology with other
      proteins, but similarities were seen in the alignment of cysteine residues in the
      link and in several domains of human von Willebrand factor, as well as cysteine
      rich areas of bovine and porcine submaxillary mucins and a frog skin mucin
      designated FIM-B.1. In keeping with earlier demonstrations of the presence of
      mannose in the 118-kDa glycopeptide, there were several (13) consensus sequences
      for attachment of N-linked oligosaccharides within the link domain. Further
      sequencing of MLP 2677 in a direction 5' to the codon specifying the NH2-terminal
      proline of the link has revealed a coding region for 148 amino acids, including a
      unique 75-amino acid domain rich in cysteine and proline, and a region containing
      4.5-variable tandem repeats (each 11-12 amino acids) rich in serine, threonine,
      and proline. The presence of mucin-like tandem repeats suggests that the entire
      cysteine-rich link peptide represents the carboxyl-terminal region (75.5 kDa) of
      a mucin-like peptide (MLP). The latter is estimated to have a molecular mass of
      approximately 300 kDa.

PMID- 1372001
TI  - Identification of a novel mammalian annexin. cDNA cloning, sequence analysis, and
      ubiquitous expression of the annexin XI gene.
AB  - Annexins (or lipocortins) are a family of at least 10 structurally related
      calcium- and phospholipid-binding proteins. Each protein consists of a conserved
      core domain having four (or eight) repeats of a segment approximately 70 amino
      acids in length and a nonconserved, usually short, amino-terminal domain. To
      date, amino acid sequences for eight distinct mammalian annexins have been
      predicted from cDNAs. This report describes an additional member of this family,
      bovine annexin XI, identified by cDNA cloning and sequence analysis. The 503
      amino acid deduced protein consists of a core domain of four annexin repeats and
      a long amino-terminal domain rich in glycine, proline, and tyrosine. This novel
      annexin gene is expressed in a wide variety of tissues and isolated cells in
      culture.

PMID- 1372000
TI  - Polyoma virus middle T antigen-pp60c-src complex associates with purified
      phosphatidylinositol 3-kinase in vitro.
AB  - Reconstitution of the polyoma virus middle T antigen (mT)-pp60-src complex and
      phosphatidylinositol 3-kinase (PtdIns 3-kinase) has been accomplished in vitro
      with immunopurified baculovirus-expressed mT-pp60c-src and PtdIns 3-kinase
      purified from rat liver. Both the 110- and 85-kDa subunits of the PtdIns 3-kinase
      associated with the mT-pp60c-src complex. The association of PtdIns 3-kinase with
      the mT-pp60c-src complex was dependent on the protein-tyrosine kinase activity of
      pp60c-src as a kinase-inactive mutant (pp60(295c-src)) still complexed with mT,
      but the mT-pp60(295c-src)) complex was unable to bind PtdIns 3-kinase. The mT
      pp60c-src complex phosphorylated both subunits of PtdIns 3-kinase on tyrosine
      residues. The immunopurified mT-pp60c-src complex also associated with PtdIns 3
      kinase activity from whole cell lysates, and this association was dependent upon
      the protein-tyrosine kinase activity of pp60c-src. Comparison of 35S-labeled
      proteins from whole cell lysates which associated with immunopurified mT-pp60c
      src and mT-pp60(295c-src) revealed proteins of 110 and 85 kDa as the major
      peptides dependent on protein-tyrosine kinase activity for association with the
      complex. In addition, a synthetic phosphopeptide (13-mer) containing sequences
      conserved between the major tyrosine phosphorylation site of murine polyoma virus
      mT, hamster polyoma virus mT, and the insulin receptor substrate (IRS-1)
      specifically blocked the association of the 85- and 110-kDa polypeptides with the
      mT-pp60c-src complex. The ability to block the association was dependent on the
      tyrosine phosphorylation of the peptide. Association of PtdIns 3-kinase activity
      was blocked concurrently. This is the first demonstration that the 110-kDa
      subunit of PtdIns 3-kinase can associate with mT-pp60c-src. This association in
      vitro is a step toward understanding protein-protein interactions important in
      the signal transduction pathway of oncogenic proteins.

PMID- 1372002
TI  - Fc epsilon RI-induced protein tyrosine phosphorylation of pp72 in rat basophilic
      leukemia cells (RBL-2H3). Evidence for a novel signal transduction pathway
      unrelated to G protein activation and phosphatidylinositol hydrolysis.
AB  - Recently, we demonstrated that aggregation of the high affinity IgE receptor in
      rat basophilic leukemia (RBL-2H3) cells results in rapid tyrosine phosphorylation
      of a 72-kDa protein (pp72). Here we investigated the relationship of pp72
      phosphorylation to guanine nucleotide-binding protein (G protein) activation and
      phosphatidylinositol hydrolysis. The activation of G proteins by NaF in intact
      cells or by guanosine 5'-O-(3-thiotriphosphate) in streptolysin O-permeabilized
      cells induced both phosphatidylinositol hydrolysis and histamine release without
      tyrosine phosphorylation of pp72. Similarly, in RBL-2H3 cells expressing the G
      protein-coupled muscarinic acetylcholine receptor, carbachol activated
      phospholipase C and induced secretion without concomitant pp72 phosphorylation.
      Therefore, pp72 phosphorylation was not induced by G protein activation or as a
      consequence of phosphatidylinositol hydrolysis. To investigate whether pp72
      tyrosine phosphorylation precedes the activation of phospholipase C, we studied
      the effect of the tyrosine kinase inhibitor genistein. Preincubation of cells
      with genistein decreased, in parallel, antigen-induced tyrosine phosphorylation
      of pp72 (IC50 = 34 micrograms/ml) and histamine release (IC50 = 31
      micrograms/ml). However, genistein at concentrations of up to 60 micrograms/ml
      did not inhibit phosphatidylinositol hydrolysis nor did it change the amount of
      the secondary messenger inositol (1,4,5)-triphosphate. Previous observations
      showed that there was no pp72 tyrosine phosphorylation after activation of
      protein kinase C or after an increase in intracellular calcium. Taken together,
      these results suggest that pp72 tyrosine phosphorylation represents a distinct,
      independent signaling pathway induced specifically by aggregation of the Fc
      epsilon RI.

PMID- 1372003
TI  - Thrombomodulin is preferentially expressed in Balb/c lung microvessels.
AB  - Previously, two rat monoclonal antibodies where developed which bind distinct
      epitopes on a murine glycoprotein, P112, which is expressed primarily in lung
      capillary endothelium. In this paper we show that P112 is identical to the
      endothelial anticoagulant protein, thrombomodulin (TM). Several lines of evidence
      support this conclusion. First, amino acid analysis of P112 shows a high degree
      of homology to TM, and both molecules exhibit the same mobility in gel
      electrophoresis. Second, P112 and TM share reactivity for two different
      monoclonal antibodies. Third, purified P112, like TM, acts as a cofactor for
      protein C activation. Finally, two cDNA clones identified with P112 polyclonal
      antiserum contain sequence identity with the known TM cDNA sequence. Quantitative
      analysis of TM (P112) expression using a two-site monoclonal antibody assay
      demonstrates that significantly higher levels of TM are found in lung in
      comparison with other highly vascularized organs, i.e. the kidney and liver.
      Quantitative Northern blot data coincides with the two-site assay data and
      demonstrates that the high level of TM expression in lung is not due to
      preferential binding of the monoclonal antibodies to lung TM but rather to
      increased production of TM mRNA in the lung relative to other highly vascularized
      organs. It is suggested that expression of TM is highest in cells from continuous
      endothelium.

PMID- 1372004
TI  - Activation of Fc gamma RII induces tyrosine phosphorylation of multiple proteins
      including Fc gamma RII.
AB  - Platelets provide a useful system for studying Fc gamma receptor-mediated
      signaling events because these cells express only a single class of Fc gamma
      receptors and because platelet aggregation and secretion can be activated through
      Fc gamma receptor stimulation. We report here that stimulation of platelets by
      cross-linking antibodies to Fc gamma RII or by treatment with an anti-CD9
      monoclonal antibody, which acts through Fc gamma RII, causes an induction of
      tyrosine phosphorylation of multiple platelet proteins. Although the profile of
      tyrosine-phosphorylated proteins induced by stimulation of this Fc receptor was
      similar to that induced by thrombin, an additional 40-kDa phosphorylated protein
      was also detected. This protein co-migrated with Fc gamma RII and was
      immunoprecipitated with a monoclonal antibody to Fc gamma RII. In addition, after
      the cross-linking of Fc gamma RII in HEL cells or in COS-1 cells transfected with
      Fc gamma RII cDNA, the 40-kDa protein immunoprecipitated with anti-Fc gamma RII
      was also phosphorylated on tyrosine. These data strongly suggest that Fc gamma
      RII itself is a substrate for a tyrosine kinase(s) activated when Fc gamma RII is
      stimulated. Fc gamma RII was phosphorylated by the Src protein in vitro,
      suggesting that this kinase may be responsible for phosphorylation of Fc gamma
      RII in vivo. These studies establish that activation of platelets and human
      erythroleukemia cells through Fc gamma RII and CD9 involves an induction of
      tyrosine phosphorylation of multiple proteins including Fc gamma RII itself and
      suggest that these phosphorylation events may be involved in Fc gamma RII
      mediated cell signaling.

PMID- 1372005
TI  - Cellular differentiation is required for cAMP but not Ca(2+)-dependent Cl-
      secretion in colonic epithelial cells expressing high levels of cystic fibrosis
      transmembrane conductance regulator.
AB  - The gene responsible for cystic fibrosis (CF) has recently been cloned and
      sequenced. When transfected into CF epithelial cells, normal transcripts of this
      gene correct the underlying defect in CF, i.e. cAMP-dependent Cl- secretion is
      restored. Thus, the protein encoded by this gene, designated "cystic fibrosis
      transmembrane conductance regulator" (CFTR), somehow participates in the Cl-
      secretory response. In this paper we have correlated CFTR gene expression with
      cAMP and Ca(2+)-dependent Cl- secretion in unpolarized (parental) and polarized
      (Cl.19A) clones of the human colonic adenocarcinoma cell line HT-29. These cell
      lines were found to express equally high levels of CFTR mRNA at 4 days post
      passage. In addition, protein expression (determined by immunoprecipitation) was
      also identical. The cAMP-generating agonist forskolin had little effect on 125I
      efflux from the unpolarized cells. In contrast, this agonist increased 125I
      efflux 3-fold in polarized cells. The lack of response in the unpolarized cells
      was not due to the inability of forskolin to raise cAMP levels. Neurotensin, a
      Ca(2+)-mobilizing agonist, stimulated 125I efflux from both cell lines. In the
      polarized cells, the magnitude of this response was attenuated at 8 days post
      seeding. At this time, the undifferentiated line attained some cAMP
      responsiveness. This latter effect was paralleled by the appearance of monolayers
      within areas of the multicell layer. Cell-attached patch-clamp recording from
      apical membrane patches of polarized cells revealed the presence of a forskolin
      stimulated 8-pS Cl- channel; no channel activity was observed in forskolin
      stimulated unpolarized cells. Ca(2+)-activated Cl- channels were found in both
      cell lines. In agreement with the 125I efflux data, the single-channel activation
      response to [Ca2+]i was smaller in the polarized cell line. From these studies,
      we can conclude that CFTR expression, measured both at the mRNA and protein
      level, does not correlate with the colonocyte's ability to secrete chloride ions
      in response to a cAMP-generating agonist. Cyclic AMP-dependent Cl- secretion
      requires cellular polarization; specifically, the delineation of an apical
      membrane. Differences in the cellular location of CFTR during differentiation are
      likely to explain our results. In contrast, Ca(2+)-stimulated Cl- secretion
      occurred independently of cellular polarization but was reduced when the cells
      formed tight junctions.

PMID- 1372006
TI  - Aggrecan core protein is expressed in membranous bone of the chick embryo.
      Molecular and biomechanical studies of normal and nanomelia embryos.
AB  - The recessive mutation nanomelia blocks the synthesis of a large aggregating
      proteoglycan (aggrecan) by avian embryo chondrocytes. Lack of aggrecan is
      associated with short stature, multiple morphological defects in cartilage, and
      embryo lethality. Bony defects have also been described, but were assumed to be a
      secondary consequence of the cartilage defect. However, two lines of evidence
      presented in this paper indicate that the aggrecan deficiency directly affects
      intramembranous bone. First, the morphology (i.e. projected area and shape) of
      certain membranous bones of nanomelia embryos was abnormal. Second, membranous
      bone from nanomelia embryos proved to be significantly stiffer in biomechanical
      tests that measured functional properties of the extracellular matrix. These
      findings were unexpected because intramembranous bones normally develop from
      mesenchyme and not from a cartilage intermediate, and they prompted a search for
      evidence of aggrecan expression in the bone of normal chick embryos. We report
      that: 1) aggrecan mRNA was identified by PCR analysis of total RNA isolated from
      day-13 chick embryo calvarium, 2) the PCR method successfully amplified aggrecan
      mRNA from primary chick embryo osteoblasts in culture, 3) in situ hybridization
      of membranous bone tissue sections demonstrated aggrecan expression by chick
      embryo osteoblasts in vivo, and 4) the aggrecan message was identified in
      Northern blots of calvarial mRNA probed at high stringency. The results of the
      molecular and biomechanical studies provide evidence that aggrecan is indeed
      expressed in membranous bone as well as cartilage. Altogether, these results
      suggest that aggrecan may contribute to the functional properties and the normal
      growth and development of avian membranous bone.

PMID- 1372007
TI  - Transcriptional activation of fibroblast collagenase gene expression by a novel
      lymphokine, leukoregulin.
AB  - Leukoregulin (LR) is a novel T-cell derived cytokine with unique anti-tumor
      properties. We have recently demonstrated that LR is also able to modulate the
      biosynthetic repertoire of normal human skin fibroblasts in culture (Mauviel, A.,
      Redini, F., Hartmann, D.J., Pujol, J.-P., and Evans, C.H. (1991) J. Cell Biol.
      113, 1455-1462). In this study, we have examined in detail the effects of LR on
      collagenase gene expression in human skin fibroblast cultures. The results
      indicated time- and dose-dependent induction of collagenase mRNA steady-state
      levels, the maximum elevation being approximately 35-fold. In contrast, the mRNA
      levels for tissue inhibitor of metalloproteases remained unchanged in the same
      RNA preparations. The enhancement of collagenase mRNA levels was shown to be
      dependent on protein synthesis, and it could be counteracted by dexamethasone or
      all-trans-retinoic acid. Transient transfections of cultured fibroblasts with a
      human collagenase promoter/reporter gene construct indicated up-regulation of the
      promoter activity, which could be blocked by dexamethasone and all-trans-retinoic
      acid. The observation suggested regulation at the transcriptional level of
      collagenase gene expression. LR was also shown to induce the mRNA levels for
      junB, suggesting possible involvement of the AP-1 complex in the regulation. The
      ability of LR to selectively induce collagenase gene expression in skin
      fibroblasts suggests that this cytokine may significantly contribute to the
      degradation of the extracellular matrix in physiological situations, such as
      tissue development and repair, and in diseases characterized by excessive
      degradation and turnover of collagen.

PMID- 1372008
TI  - Membrane dynamics of the phosphatidylinositol-anchored form and the transmembrane
      form of the cell adhesion protein LFA-3.
AB  - The cell adhesion glycoprotein LFA-3 is expressed on the cell surface of
      nucleated cells in both a membrane-spanning form and a glycosyl
      phosphatidylinositol-anchored form. To determine whether distinct membrane
      anchors direct the dynamics of a given protein, the turnover of biosynthetically
      35S-labeled and biotin surface-labeled LFA-3 molecules was followed. It is shown
      here that (a) expression of the two LFA-3 forms is regenerated with similar
      kinetics after enzymatic removal from the cell surface; (b) neither of the
      distinct LFA-3 molecules undergoes constitutive internalization; and (c)
      transmembrane and glycosyl phosphatidylinositol-anchored LFA-3 have an unusually
      long life span with an identical half-life of 50 h. Thus, the type of membrane
      anchor is not affecting turnover characteristics of a particular cell surface
      glycoprotein.

PMID- 1372009
TI  - Identification of a heparin-binding growth factor-1 nuclear translocation
      sequence by deletion mutation analysis.
AB  - We have shown previously that a deletion mutant of human heparin-binding growth
      factor (HBGF)-1, HBGF-1U, lacking the sequence Asn-Tyr-Lys-Lys-Pro-Lys-Leu is
      capable of initiating c-fos mRNA expression and polypeptide phosphorylation on
      tyrosine residues at concentrations that do not induce either DNA synthesis or
      cell proliferation (1). The fact that addition of the nuclear translocation
      signal from the yeast histone 2B protein to the HBGF-1U mutant caused
      reconstitution of the biological activity of HBGF-1 indicated that nuclear
      translocation may be an important component of the mitogenic signal induced by
      HBGF-1. In order to examine the nuclear translocation potential of HBGF-1 alpha,
      the deletion mutant HBGF-1U, and the yeast histone 2B-HBGF-1 chimera, HBGF-1U2,
      we expressed these forms of HBGF-1 in murine endothelial cells. Western blot and
      two-dimensional Western blot analysis of cytosol and nuclei demonstrate that
      although the three forms of HBGF-1 are readily detectable in the cytosol of the
      individual transfectants, HBGF-1 alpha and HBGF-1U2 but not HBGF-1U was detected
      in the nucleus. Furthermore, murine endothelial cells expressing HBGF-1 alpha and
      HBGF-1U2 exhibited an atypical cellular phenotype in vitro that was absent in the
      HBGF-1U transfectants. These data suggest that HBGF-1 contains a functional
      nuclear translocation sequence that may be responsible for the initiation of DNA
      synthesis, and these data further correlate the presence of the nuclear
      translocation sequence with an abnormal endothelial cell phenotype in vitro.

PMID- 1372010
TI  - Efferent connections of the centromedian and parafascicular thalamic nuclei in
      the squirrel monkey: a PHA-L study of subcortical projections.
AB  - The subcortical projections of the centromedian (CM) and the parafascicular (Pf)
      thalamic nuclei were examined in the squirrel monkey (Saimiri sciureus) by using
      the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) as an anterograde tracer.
      Both CM and Pf project massively to the striatum where they arborize in a
      complementary fashion. On the one hand, CM innervates most of the putamen caudal
      to the anterior commissure, a dorsolateral rim of the putamen rostral to the
      anterior commissure, discrete areas of the head of the caudate nucleus close to
      the internal capsule, and a lateral sector of the body of the caudate nucleus. On
      the other hand, Pf provides a heavy input to the head, body, and tail of the
      caudate nucleus, and to the rostral putamen, excluding the areas innervated by
      CM. In addition, Pf projects more discretely to the nucleus accumbens and the
      olfactory tubercle. Therefore, the projections from both CM and Pf cover the
      entire striatum, with those from CM arborizing into the "sensorimotor" striatal
      territory and the ones from Pf innervating the "associative-limbic" striatal
      territory. Furthermore, CM and Pf project to extrastriatal subcortical
      structures, such as the globus pallidus, the subthalamic nucleus, and the
      substantia nigra, where they also terminate in a complementary fashion.
      Topographically and cytologically, Pf is closely related to the subparafascicular
      nucleus (sPf). The Pf-sPf complex projects to the hypothalamus, the substantia
      innominata, the peripeduncular nucleus, and the amygdala. It also gives rise to
      descending efferents arborizing in various brainstem structures, including the
      inferior olivary complex. Additional studies with retrograde double-labeling
      methods show that distinct cell groups within CM project to the motor cortex and
      the striatum. Likewise, separate neuronal populations within the CM-Pf-sPf
      complex give rise to striatal and brainstem projections, the former arising from
      CM and Pf and the latter mainly from sPf. The complementary nature of CM and Pf
      projections to the striatum and other basal ganglia components suggests that this
      thalamic complex participates in a highly ordered manner in the parallel
      processing of the information that flows through the basal ganglia.

PMID- 1372011
TI  - Altered expression of pp60c-src induced by peripheral nerve injury.
AB  - The normal src protein (pp60c-src) is localized principally in the nerve growth
      cone of developing neurons and declines to low levels with synaptic maturation.
      To determine whether pp60c-src is reexpressed in regenerating axons, its
      expression was studied by immunoblotting and immunocytochemical analyses in adult
      chicken sciatic nerve following nerve crush injury. pp60c-src expression was
      found to increase during nerve repair with a temporal and spatial pattern
      consistent with a localization in regenerating axons. At the crush site, pp60c
      src increased to maximal levels 7 days postinjury, increasing fivefold relative
      to 0 day nerve. In the nerve segment distal to the injury, the maximal increase
      in pp60c-src was sevenfold and occurred between 11 and 21 days postinjury.
      Immunoperoxidase staining revealed pp60c-src in regenerating axons and certain
      nonneuronal cells at the site of nerve repair. pp60c-src was induced in both
      motor and sensory neurons, as shown by increased pp60c-src immunoreactivity in
      their cell bodies located in the spinal cord and dorsal root ganglion.
      Phosphotyrosine-modified proteins that were potential targets of pp60c-src
      increased following nerve crush, and were localized to outgrowing neurites as
      well as to nonneuronal cells. These results suggest that pp60c-src is a common
      component of cellular mechanisms regulating growth cone migration in both
      regenerating and developing axons.

PMID- 1372012
TI  - Postnatal development of the corticotectal projection in cats.
AB  - Although numerous physiological studies have provided compelling evidence for the
      involvement of the corticotectal projection in the normal development of visual
      response properties of neurons in the superior colliculus, little information is
      available on the morphological development of corticotectal axons. Thus, our goal
      was to determine the postnatal changes characterizing the development of the
      topography and morphology of corticotectal axon arbors. Topographically
      restricted injections of Phaseolus vulgaris leucoagglutinin were made into
      striate cortex to label corticotectal axons and their terminal arbors. Following
      injections of similar size and location in kittens and adult cats, a similar,
      localized region of the superior colliculus was labeled at all ages. However,
      while present in the appropriate topographic location in colliculus, the
      corticotectal projection revealed a greater tangential distribution in kittens
      than adults. Corticotectal terminal zones underwent a twofold decrease in
      tangential area during the first 8 weeks after birth. From corticotectal terminal
      zones in kittens, extended many fine collaterals that ended as growth cones and
      radiated up to 1 mm from the focus of the terminal zone. By 8 weeks after birth,
      these immature collaterals were no longer observed, and the corticotectal
      terminal zone was indistinguishable from those in 12-week-old kittens and adult
      cats. Corticotectal axon arbors became more specialized in the first 8 weeks
      after birth; both en passant and terminal swellings increased in diameter, and
      terminal swellings increased in number, although the total number of swellings
      per unit length of axon remained relatively stable. The number of axonal branches
      increased threefold between 1 and 8 weeks after birth. Thus, as the corticotectal
      projection becomes spatially restricted during development, individual arbors
      become progressively more intricate with regard to focused collateral branching
      and the elaboration of complex axonal specializations.

PMID- 1372013
TI  - Intrinsic circuitry in the cat superior colliculus: projections from the
      superficial layers.
AB  - The neuroanatomical tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was used to
      label the local projections of neurons whose cell bodies are located in the
      superficial layers of the cat superior colliculus. Small, localized groups of
      neurons in the superficial layers project to all regions of the ipsilateral
      colliculus, including the deep layers. Comparable distributions of labeled
      terminals are seen throughout the colliculus when the PHA-L injection site is
      located in the rostral, middle, or caudal one-third of the colliculus. In
      addition, there is some evidence of a topographic projection from superficial to
      deep layers. These results suggest that a complex anatomical substrate exists for
      communication between the superficial and deep layers of the colliculus.
      Connections such as these may underlie the transfer of visual information from
      neurons in the superficial layers to populations of neurons in the deep layers
      that respond prior to saccadic eye movements.

PMID- 1372014
TI  - The Fontan operation in infants less than 2 years of age.
AB  - Young age remains a reported risk factor for a successful Fontan operation
      despite improved survival rates. Since March 1978, the Fontan operation has been
      performed in 47 patients. To avoid a primary or secondary palliative shunt, an
      early Fontan procedure (Group 1: mean age 1.5 +/- 0.5 years, range 0.6 to 2) has
      been performed in 17 children with the outcome similar to that of the remaining
      30 older patients (Group 2: mean age 7.5 +/- 5 years, range 2.4 to 23 years).
      Preoperatively both groups had acceptable hemodynamic status for a successful
      Fontan result. Operative variables including cardiopulmonary bypass time, aortic
      cross-clamp time and core temperature were similar between groups and did not
      affect mortality. The postoperative mortality rate including early surgical (0%
      vs. 13%, respectively), late (18% vs. 12%) and total (18% vs. 23%) was similar
      between Groups 1 and 2 (p greater than 0.05). Immediate postoperative arrhythmias
      were more frequent in Group 1 (71% vs. 25%, p less than 0.01) with no related
      mortality, while late arrhythmias occurred with equal frequency (29% vs. 39%, p
      greater than 0.05). Group 1 infants required a longer hospital stay (22 +/- 9 vs.
      14 +/- 5 days, p less than 0.01). Thus, young age is not a risk factor for
      successful outcome of the Fontan operation in patients with acceptable
      preoperative hemodynamic status. An early Fontan operation may also avoid
      prolonged palliative procedures and their potential deleterious effects.

PMID- 1372015
TI  - Response of the pulmonary circulation to acetylcholine, calcitonin gene-related
      peptide, substance P and oral nicardipine in patients with primary pulmonary
      hypertension.
AB  - Endothelium-dependent vasodilation of the pulmonary vascular bed was investigated
      in five patients with primary pulmonary hypertension. Three endothelium-dependent
      vasodilators (acetylcholine, calcitonin gene-related peptide and substance P [in
      two patients]) were infused sequentially into the right atrium, followed by
      nicardipine given orally during full hemodynamic monitoring. Acetylcholine,
      calcitonin gene-related peptide and substance P had no effect on pulmonary artery
      pressure, total pulmonary vascular resistance or cardiac output, although
      calcitonin gene-related peptide significantly decreased systemic arterial
      systolic pressure from 132 +/- 34 to 113 +/- 33 mm Hg. In contrast, oral
      nicardipine decreased total pulmonary vascular resistance from 23 +/- 12 to 13 +/
      8 U, with a concomitant increase in cardiac output from 3.1 +/- 1 to 4.7 +/- 2
      liters.min-1 and decrease in systemic vascular resistance from 30 +/- 9 to 13 +/-
      4 U. Thus, despite the presence of a reversible component in these five patients
      with primary pulmonary hypertension, pulmonary vascular resistance did not
      decrease in response to the infused endothelium-dependent vasodilator agents,
      indicating that endothelium-dependent vasodilation is impaired in these patients.

PMID- 1372016
TI  - Connective tissue-activating peptide-III and its derivative, neutrophil
      activating peptide-2, release histamine from human basophils.
AB  - Connective tissue-activating peptide-III (CTAP-III) is a 9 kd platelet alpha
      granule-derived growth factor. It stimulates the synthesis of DNA, hyaluronic
      acid, glycosaminoglycans, and proteoglycan core protein in human fibroblasts.
      Human mononuclear cell-derived proteases have been previously demonstrated to
      digest the N-terminal 15 residues of CTAP-III (total, 85 residues) to produce
      neutrophil-activating peptide-2 (NAP-2). CTAP-III and NAP-2 belong to a class of
      proteins (platelet factor 4, interleukin-8/NAP-1, etc.) associated with
      inflammation and wound repair. In our efforts to purify human mononuclear cells
      and platelet-derived histamine-releasing factors, we had previously discovered
      that mixtures of CTAP-III and NAP-2 released histamine from human basophils. We
      have now developed simple protocols for the purification of CTAP-III and NAP-2,
      independently, from calcium ionophore (A23187)-stimulated platelet supernatants
      by affinity chromatography and have established their identity by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and N-terminal sequence analysis. Each
      of these related histamine between 2 and 10 micrograms/ml, a range identical to
      that obtained with CTAP-III/NAP-2 mixtures that we reported earlier. Thus, our
      data suggest that CTAP-III and NAP-2 independently release histamine from human
      basophils in dose ranges similar to ranges required for fibroblast stimulation by
      each.

PMID- 1372017
TI  - Class I-specific antibodies inhibit proliferation in primary but not secondary
      mouse T cell responses.
AB  - Murine T and B splenocytes were incubated with antibodies that recognize CD3 or
      surface IgM. These antibodies induced proliferation of their respective target
      cells. Once stimulated via their receptors, the proliferation of both CD4+ and
      CD8+ T but not B lymphocytes was inhibited by class I-specific antibodies or
      their monovalent Fab' fragments. The inhibition of proliferation was dependent on
      the site on class I molecules recognized by the antibodies used, with the alpha
      1/alpha 2 domains of H-2K molecules representing the major site for inhibition.
      Only soluble antibody-mediated proliferation could be inhibited by class I
      directed antibodies; proliferation induced by CD3-specific antibody immobilized
      on plastic was not inhibited. Primary allogeneic MLR was also inhibited by class
      I-specific antibodies. In contrast, neither secondary allogeneic MLR, secondary
      Ag-specific responses, nor proliferation of CTL clones or tumor cell lines were
      inhibited by class I-specific antibodies. These results suggest a role for class
      I molecules in regulation of TCR/CD3- but not surface IgM-mediated cell
      signaling, which depends on the form of stimulation and the stage of
      differentiation of T cells.

PMID- 1372018
TI  - Differential costimulatory effects of adhesion molecules B7, ICAM-1, LFA-3, and
      VCAM-1 on resting and antigen-primed CD4+ T lymphocytes.
AB  - Optimal proliferation of T cells although initiated via ligation of the CD3/TCR
      complex requires additional stimulation resulting from adhesive interactions
      between costimulatory receptors (R) on T cells and their counter-R on APC. At
      least four distinct adhesion molecules (counter-R) present on APC, B7, ICAM-1
      (CD54), LFA-3 (CD58), and VCAM-1 have been individually shown to costimulate T
      cell activation. Because some of these molecules may be expressed simultaneously
      on APC, it has been difficult to examine relative contributions of individual
      counter-R during the induction of T cell proliferation. We have produced soluble
      IgC gamma 1 fusion chimeras (receptor globulins or Rg) of B7, ICAM-1, LFA-3, and
      VCAM-1 and compared their relative abilities to costimulate proliferation of
      resting or Ag-primed CD4+ T cells. When co-immobilized with mAb directed at TCR
      alpha beta or CD3 but not CD2 or CD28, each Rg induced proliferation of both
      resting and Ag-primed CD4+ cells. In contrast, similarly co-immobilized CD7 Rg or
      ELAM-1 Rg were ineffective. Resting CD4+ T cells produced more IL-2, expressed
      significantly higher levels of IL-2R alpha, and proliferated more efficiently
      when costimulated with either ICAM-1 Rg or VCAM-1 Rg than with B7 Rg or LFA-3 Rg.
      CD4+ CD45RO+ memory T cells proliferated more vigorously in response to the
      costimulation by each of the four Rg than CD4+ CD45RA+ naive T cells. In contrast
      with the behavior of resting CD4+ T cells, proliferation of Ag-preactivated CD4+
      T cells was most efficient when costimulated by B7 Rg. The costimulatory effect
      of LFA-3 Rg on Ag-primed CD4+ T cells was weaker than that of B7 Rg but was
      significantly greater than that of either ICAM-1 Rg or VCAM-1 Rg. These results
      suggest that resting and Ag-primed CD4+ T cells preferentially respond by
      proliferation to different costimulatory counter-R. ICAM-1 and VCAM-1 may be
      involved in the initiation of proliferation of Ag-responsive T cells, and B7 and
      LFA-3 may facilitate sustained proliferation of Ag-primed T cells. The cumulative
      costimulation by the above counter-R may facilitate optimal expression of various
      regulatory and effector functions of T cells.

PMID- 1372019
TI  - Membrane Ig cross-linking regulates phosphatidylinositol 3-kinase in B
      lymphocytes.
AB  - Cross-linking of the B cell AgR results in activation of mature B cells and
      tolerization of immature B cells. The initial signaling events stimulated by
      membrane immunoglobulin (mIg) cross-linking are tyrosine phosphorylation of a
      number of proteins. Among the targets of mIg-induced tyrosine phosphorylation are
      the tyrosine kinases encoded by the lyn, blk, fyn, and syk genes, the mIg
      associated proteins MB-1 and Ig-beta, phospholipase C-gamma 1 and -gamma 2, as
      well as many unidentified proteins. In this report we show that mIg cross-linking
      also regulates phosphatidylinositol 3-kinase (PtdIns 3-kinase), an enzyme that
      phosphorylates inositol phospholipids and plays a key role in mediating the
      effects of tyrosine kinases on growth control in fibroblasts. Cross-linking mIg
      on B lymphocytes greatly increased the amount of PtdIns 3-kinase activity which
      could be immunoprecipitated with anti-phosphotyrosine (anti-tyr(P) antibodies.
      This response was observed after mIg cross-linking in mIgM- and mIgG-bearing B
      cell lines and after cross-linking either mIgM or mIgD in murine splenic B cells.
      Thus, regulation of PtdIns 3-kinase is a common feature of signaling by several
      different isotypes of mIg. This response was rapid and peaked 2 to 3 min after
      the addition of anti-Ig antibodies. The anti-Ig-stimulated increase in PtdIns 3
      kinase activity associated with anti-Tyr(P) immunoprecipitates could reflect
      increased tyrosine phosphorylation of PtdIns 3-kinase, increased activity of the
      enzyme, or both. In favor of the first possibility, the tyrosine kinase inhibitor
      herbimycin A blocked the increase in ant-Tyr(P)-immunoprecipitated PtdIns 3
      kinase activity as well as the anti-Ig-induced tyrosine phosphorylation.
      Moreover, this response was not secondary to phospholipase C activation but
      rather seemed to be a direct consequence of mIg-induced tyrosine phosphorylation.
      Activation of the phosphoinositide pathway by a transfected M1 muscarinic
      acetylcholine receptor expressed in WEHI-231 B lymphoma cells did not increase
      the amount of PtdIns 3-kinase activity which could be precipitated with anti
      Tyr(P) antibodies. Similarly, inhibition of the phosphoinositide pathway did not
      abrogate the ability of mIg cross-linking to stimulate this response. Thus, mIg
      induced tyrosine phosphorylation regulates PtdIns 3-kinase, an important mediator
      of growth control in fibroblasts and potentially an important regulatory
      component in B cells as well.

PMID- 1372020
TI  - CD2/LFA-3 ligation induces phospholipase-C gamma 1 tyrosine phosphorylation and
      regulates CD3 signaling.
AB  - Activation of T cells through the TCR/CD3 receptor complex with either specific
      Ag or antibody results in tyrosine phosphorylation of intracellular protein
      substrates and phosphatidylinositol-phospholipase C (PLC) signaling, leading to
      the generation of PI breakdown products and the mobilization of intracellular
      calcium. Stimulation of the T cell surface receptor CD2 similarly propagates
      early signals through phosphatidylinositol-PLC activation. Previous reports have
      shown that CD3 activation leads to tyrosine phosphorylation of the PLC isozyme
      PLC gamma 1. In this report, we investigated the potential similarity between CD3
      induced signaling through PLC gamma 1 and that induced by CD2. We show that
      stimulation of CD2 receptors on T cells caused tyrosine phosphorylation of PLC
      gamma 1. Cross-linking of CD2 with CD3 receptors augmented the phosphorylation of
      PLC gamma 1 on tyrosine, whereas ligation of the CD45 tyrosine phosphatase with
      CD2 receptors prevented PLC gamma 1 tyrosine phosphorylation. T cells stimulated
      by ligation of CD2 with its counter-receptor in the form of a soluble LFA-3/Ig
      fusion protein cross-linked on the cell surface, resulted in a low, but
      detectable level of PLC gamma 1 phosphorylation with prolonged kinetics, whereas
      that induced by cross-linking with anti-CD2 was stronger but transient. Co
      ligation of LFA-3/Ig with suboptimal concentrations of anti-CD3 resulted in
      profound augmentation of PLC gamma 1 tyrosine phosphorylation, mobilization of
      intracellular calcium and T cell proliferation. To explore the relationship
      between CD3- and CD2-stimulated signaling, T cells were desensitized through 1 h
      incubation with anti-CD3. CD3 receptor modulation potently down-regulated CD2
      induced PLC gamma 1 tyrosine phosphorylation and calcium mobilization. In
      contrast, PMA or ionomycin treatment did not alter CD2-stimulated tyrosine
      phosphorylation of PLC gamma 1, suggesting that tyrosine kinase inhibition by CD3
      receptor modulation was not caused by signaling events downstream of PLC gamma 1.
      Taken together, these results support the hypothesis that CD2 provides a potent
      co-stimulatory signal for CD3-induced T cell activation that is associated with
      tyrosine kinase(s) and PLC gamma 1.

PMID- 1372021
TI  - Antigen-specific stimulation of T cell extracellular acidification by MHC class
      II-peptide complexes.
AB  - A specific T cell response to a preformed complex of detergent-solubilized MHC
      class II molecule and cognate antigenic peptide was observed by monitoring the
      extracellular acidification. An increase in this rate was observed when the
      resting 4R3.9 T cell clone specific for the peptide fragment MBP(1-14) of myelin
      basic protein was exposed to preformed detergent-solubilized IAk-MBP(1-14)A4
      complexes. MBP peptide alone, IAk alone, or complexes of IAs-proteolipid
      protein(139-151) and IAd-OVA(323-339), did not cause significant increases in the
      acidification rates of the MBP(1-14)-restricted 4R3.9 T cell clone. In addition,
      BW 5147 T lymphoma cells, which lack TCR, did not show any increase in rate when
      exposed to IAk-MBP(1-14)A4 complexes. Similar increases in acidification rate
      were observed in the presence of IL-2, anti-CD3 and anti-TCR antibodies. The
      enhanced acidification responses were blocked by genistein, a tyrosine kinase
      inhibitor.

PMID- 1372022
TI  - Linear epitope mapping of an Sm B/B' polypeptide.
AB  - Autoantibodies binding the Sm B/B' peptides are commonly associated with SLE. IgG
      antibodies binding overlapping octapeptides of Sm B/B' have been evaluated in 10
      patients with anti-Sm and anti-nRNP precipitins, 5 patients with other autoimmune
      serology, and 4 normal human sera. Neither normal controls nor patients without
      an anti-Sm precipitin significantly bind any of the Sm B/B' octapeptides. All
      sera tested containing an anti-Sm precipitin strongly bind octapeptides from
      eight regions of the Sm B/B' sequence. Three of these eight regions share the
      same octapeptide sequences (PPPGMRPP) that are consistently the most
      immunoreactive octapeptides from Sm B/B'. Binding of the similar PPPGIRGP, as
      well as binding to deletion and substitution peptides, suggest that the motif
      PPPG(I,M) (R,K) appears to best define this binding. Interestingly, PAPGMRPP in
      the nRNP C peptide is as antigenic as PPPGMRPP and may provide a partial
      explanation for the cross-reactivity shown between Sm and nRNP autoantibodies.
      However, the sequence, PPPGMIPP, from nRNP A is not antigenic. These data define
      the linear sequence autoantigenicity of the Sm B/B' protein. They also
      demonstrate that the predominant autoimmune epitope is a proline-rich sequence
      from which limited variance is permitted before antigenicity is destroyed.

PMID- 1372023
TI  - Identification of thyroiditogenic epitope on porcine thyroid peroxidase for
      C57BL/6 mice.
AB  - C57BL/6 mice show thyroid lesions when immunized with porcine thyroid peroxidase
      (pTPO) emulsified in CFA. We attempted to clarify a thyroiditogenic epitope on
      pTPO. Thyroid peroxidase treated with cyanogen bromide was fractionated by
      reverse phase chromatography, and six fractions (A to F) were obtained. Two of
      these fractions (D and E) stimulated lymph node cells (LNC) primed with pTPO in
      vitro and induced thyroiditis in vivo. Tricine-SDS-PAGE and rechromatography
      showed that fraction D consisted solely of a fragment of Mr 9500 Da and that
      fraction E contained mainly fragments of Mr of 5400 and 9500 Da. The fragment of
      fraction D was rechromatographed and 20 NH2-terminal amino acids were analyzed.
      This segment was found to correspond to residue 726-745 of pTPO deduced from cDNA
      at a probability of 80%. Four peptides ranging from residue 746-827 were first
      synthesized and tested for their thyroiditogenicity. Only Pep-2 (29 amino acids)
      could stimulate LNC primed with pTPO and induce thyroiditis. Pep-2 was divided
      into two smaller peptides (Pep-2-1 and -2-2) and their thyroiditogenicity was
      tested again. Pep-2-1 corresponding to residue 774-788, GPA-QITCTPRGWDSP, had
      thyroiditogenicity as well as the ability to stimulate LNC. It was thought that
      this segment was at least one of the thyroiditogenic epitopes on porcine thyroid
      peroxidase for C57BL/6 mice.

PMID- 1372024
TI  - Characterization of proteoglycan-reactive T cell lines and hybridomas from mice
      with proteoglycan-induced arthritis.
AB  - Hyperimmunization with chondroitin sulfate-depleted fetal human cartilage
      proteoglycan (HFPG) leads to the development of peripheral arthritis and
      spondylitis in BALB/c mice. Chondroitin-sulfate-depleted adult human cartilage
      proteoglycan (HAPG) is much less effective at inducing arthritis. These
      observations suggest age differences in the presence of arthritogenic
      proteoglycan (PG) epitopes. Earlier studies from this laboratory have indicated
      an important role for PG-reactive T cells in the pathogenesis of this arthritis
      model. To investigate further the cellular immunity to PG in mice, two T cell
      lines, JY.A and JY.D, and two T cell hybridomas, TH5 and TH14, were isolated from
      mice with PG-induced arthritis and characterized. Two patterns of reactivity to
      PG emerged from the analysis of these T cells. One pattern, as demonstrated by
      the T cell line JY.D and the two T cell hybridomas, TH5 and TH14, was
      characterized by reactivity to HFPG, HAPG, chondroitin sulfate-depleted bovine
      cartilage PG, the G1 domain (hyaluronate binding region) of bovine cartilage PG
      and bovine link protein. The epitope(s) recognized by these T cells appear to be
      part of the homologous regions shared between the G1 domain and the link protein.
      The second pattern of reactivity, as demonstrated by the T cell line JY.A, was
      characterized by reactivity to HFPG but not to HAPG or the other PG Ag or bovine
      link protein. All the T cell lines and hybridomas had a CD4+, CD8- phenotype,
      possibly belonged to the TH1 subset (IL-2+, IL-4-), and were MHC class II
      restricted. These studies indicate that HFPG has T cell epitopes in common with
      HAPG (such as in the G1 domain) and different than those in HAPG. The
      significance of this data in terms of PG structure, changes with age, and
      induction of arthritis remains to be established.

PMID- 1372025
TI  - Histamine-containing cells obtained from the nose hours after antigen challenge
      have functional and phenotypic characteristics of basophils.
AB  - The pattern of mediators and appearance of cells that stain with alcian blue
      during human experimental early and late phase allergic reactions suggest that
      basophils accumulate in nasal secretions within hours of local Ag stimulation. To
      further explore whether the histamine containing cells that enter the nose after
      Ag challenge are mast cells or basophils, we studied their functional and
      phenotypic characteristics. Approximately 24 h after intranasal Ag provocation of
      subjects with allergic rhinitis, nasal lavage was performed, and the cells were
      isolated for degranulation studies, analysis of surface Ag, and viability. The
      average histamine content per alcian blue staining cell was 0.78 +/- 0.2 pg (n =
      7), similar to that reported for peripheral blood basophils. Nasal cells were
      challenged in vitro with anti-IgE, ragweed Amb a I, and FMLP and their responses
      were compared to those of peripheral blood basophils isolated simultaneously from
      the same donors. Nasal leukocytes released histamine maximally at 0.1
      micrograms/ml of anti-IgE (35.8 +/- 7.8%, n = 7) and responded to FMLP (25.4 +/-
      9.9%, n = 7). The response of the cells to ragweed Amb a I and anti-IgE was
      attenuated compared to peripheral blood basophils. Anti-IgE-induced histamine
      release was calcium and temperature dependent. Dual color immunofluorescence and
      flow cytometric analysis of the recovered nasal cells coexpressed CD18, a
      leukocyte marker not expressed by mast cells. The nasal cells consistently had
      high levels of spontaneous histamine release (19.5 +/- 2.0%, n = 22). The
      viability of all cells, assessed by erythrosin B dye exclusion, was 70 +/- 2% (n
      = 15). However, the viability of IgE-bearing cells was only 28.3 +/- 5.7% (n =
      4). The characteristics of histamine release and the nature of the cellular
      surface markers provide functional proof that the histamine-containing cells
      accumulating after nasal Ag challenge are basophils and not mast cells.

PMID- 1372026
TI  - Mapping of T helper cell epitopes by using peptides spanning the 19-kDa protein
      of Mycobacterium tuberculosis. Evidence for unique and shared epitopes in the
      stimulation of antibody and delayed-type hypersensitivity responses.
AB  - In vivo and in vitro T cell responses to overlapping 20-mer peptides that span
      the entire 19-kDa protein of Mycobacterium tuberculosis have been compared in
      three different strains of mice. Immunization of the mice with peptides and
      analysis of specific antibody production is an in vivo assay of Th cell activity.
      Peptides 1-20 and 61-80 elicited strong IgG1 responses in BALB/cJ, C57BL/10J, and
      B10.BR mice, indicating that these peptides could stimulate Th cells, possibly of
      a Th2 phenotype. T cells isolated from peptide-immunized mice were challenged in
      vitro with peptide, and their proliferative responses were analyzed. T cells from
      these three strains of mice immunized with peptides 1-20, 61-80, and 76-95 also
      responded to challenge with specific peptide in vitro. In addition, B10.BR mice
      and BALB/cJ mice showed antibody and T cell proliferative responses to peptides
      136-155 and 145-159, respectively. Thus, in vitro proliferating T cells were
      found to possess specificities for peptide epitopes that were almost identical to
      those of the antibody-producing cells. Delayed-type hypersensitivity (DTH)
      responses to these peptides were also examined in the three strains.
      Interestingly, the T cells responding in the DTH assay had Ag specificities that
      were quite different from those identified in the antibody and proliferation
      assays. These results suggested that DTH Th cells form a separate population from
      antibody Th and proliferative T cells and these populations of cells were
      differentially activated, in an Ag-specific manner.

PMID- 1372028
TI  - Acute or chronic topical retinoic acid treatment of human skin in vivo alters the
      expression of epidermal transglutaminase, loricrin, involucrin, filaggrin, and
      keratins 6 and 13 but not keratins 1, 10, and 14.
AB  - Histologic and immunocytochemical analyses were performed on cutaneous biopsies
      from 10 patients treated with retinoic acid under occlusion for 4 d compared to
      biopsies from 19 patients treated nightly for 16 weeks. Acute application of RA
      caused epidermal thickening (9 of 10 samples), stratum granulosum thickening (7
      of 10), parakeratosis (4 of 10), a marked increase in the number of cell layers
      expressing epidermal transglutaminase (7 of 10), and focal expression of two non
      epidermal keratins, K6 (8 of 10) and K13 (2 of 10), changes also observed with
      chronic treatment. Involucrin, filaggrin, and loricrin were also altered in
      samples from both acute and chronic treatment. An increased number of cell layers
      expressed both involucrin and filaggrin from both the acute (7 of 10) and chronic
      (14 of 19) treatment groups. In the acute group, loricrin expression was
      significantly reduced or absent in some regions of the epidermis (5 of 10),
      whereas most chronic samples showed an increased number of cell layers expressing
      loricrin (12 of 19). The pattern of expression of three major epidermal
      differentiation products, keratins K1, K10, and K14, was not significantly
      altered in any of the acute or chronic samples, although there was a slight
      reduction in the detection of K10 in two of the acute samples. Thus, acute
      topical RA treatment under occlusion caused substantial changes in the epidermis,
      and reproduced most, but not all of the effects of chronic treatment.

PMID- 1372027
TI  - Studies of the effect of cyclosporine in psoriasis in vivo: combined effects on
      activated T lymphocytes and epidermal regenerative maturation.
AB  - Cyclosporine (CSA) decreases lymphokine synthesis and keratinocyte proliferation
      in vitro, but its in vivo mechanism of action in treating recalcitrant psoriasis
      is incompletely understood. Ten psoriasis patients were treated with CSA (2-7.5
      mg/kg/d) with clinical improvement in nine of 10 patients. Skin biopsies before
      and after 1-3 months of CSA treatment were studied for evidence of immune and
      keratinocyte activation using immunoperoxidase and Northern blotting analysis.
      The number of activated, IL-2 receptor+ T cells in plaques after CSA treatment
      was reduced in all patients by a mean of 60%. Seven of 10 patients showed a
      decrease in keratinocyte HLA-DR expression; five of seven showed a decrease in
      gamma-IP-10 immunoreactivity, suggesting a decline in gamma interferon levels in
      plaques after CSA therapy. We studied the effect of CSA treatment in vivo on TGF
      alpha, IL-6, and keratin K16 expression, three markers of keratinocyte growth
      activation. Expression of keratinocyte TGF-alpha and IL-6, which are elevated in
      active psoriatic epidermis, did not change in these patients after CSA treatment.
      The majority of patients (five of eight) continued to express the
      hyperproliferative keratin K16 after CSA treatment. Our results suggest that the
      predominant direct mechanism of action of Cyclosporine in vivo is a diminution of
      T-cell activation in plaques, with attendant decreased lymphokine production.

PMID- 1372029
TI  - Effect of in vivo interleukin-1 on adhesion molecule expression in normal human
      skin.
AB  - We have examined the expression of three endothelial adhesion molecules
      (intercellular adhesion molecule-1 [ICAM-1], endothelial leukocyte adhesion
      molecule-1 [ELAM-1], and vascular cell adhesion molecule-1 [VCAM-1]) in normal
      human skin following intradermal injection of stratum corneum-derived interleukin
      1 alpha (SCIL-1 alpha). In control skin, constitutive expression of ICAM-1 was
      found on endothelial cells and at low levels on dermal dendritic cells but not on
      keratinocytes. ELAM-1 and VCAM-1 were present in low levels on endothelium and
      perivascular dendritic cells, respectively. SCIL-1 alpha injection produced
      marked endothelial ELAM-1 upregulation. Double staining with neutrophil elastase
      demonstrated that many ELAM-1-positive vessels contained marginating neutrophils
      and that interstitial neutrophils were clustered around ELAM-1-positive vessels.
      An increase in dermal dendritic cell ICAM-1 expression occurred and in two of
      three biopsies there was keratinocyte expression of ICAM-1 in the SCIL-1 alpha
      injected tissue. Also, there was upregulation of VCAM-1 on vascular endothelium
      and an increase in the dermal dendritic cell expression of this molecule. These
      results give in vivo confirmation that SCIL-1 alpha modulated endothelial and
      dermal dendritic cell adhesion molecule expression, and show that endothelial
      VCAM-1 is regulated in vivo by SCIL-1 alpha, thus providing a regulatable ICAM-1
      independent means of mononuclear cell recruitment.

PMID- 1372031
TI  - Assessment of palliative response in hyperthermia.
AB  - It is important that clinical studies of hyperthermia will be able to define its
      contribution to palliative therapy. A variety of validated methods has been
      developed for assessing palliative therapy but none have been used in clinical
      studies of hyperthermia. In the present paper some of the methods available for
      the assessment of palliative therapy are reviewed. The necessary criteria for
      assessment of instruments for palliation, as well as the choice of method, is
      discussed. A simple strategy is proposed: use established methods and take advice
      on which to choose; selectively add relevant items, should this be necessary; use
      assessments made by patients as well as by clinicians; use the test instruments
      at least three times (before, during and after treatment), and pre-test it on a
      small series of patients before embarking upon a major study. It is hoped that,
      by drawing attention to the availability of such methods for evaluating
      palliation, they might prove important in more accurately evaluating the role of
      hyperthermia in the palliative treatment of cancer.

PMID- 1372030
TI  - Transforming growth factor beta inhibits the action of stem cell factor on mouse
      and human hematopoietic progenitors.
AB  - In agar culture of post 5-fluorouracil mouse bone marrow cells (FUBM),
      recombinant rat stem cell factor (rrSCF) synergizes with granulocyte colony
      stimulating factor (G-CSF), interleukin-3 (IL-3) or interleukin-6 (IL-6) to
      stimulate primitive progenitor cells (HPP-CFCs). The addition of recombinant
      human transforming growth factor beta (rhTGF-beta) to cultures of FUBM containing
      rrSCF plus rhG-CSF, rrSCF plus recombinant murine (rm)IL-3, or rrSCF plus rhIL-6
      resulted in 100% inhibition of colony formation. Highly enriched populations of
      primitive bone marrow cells were obtained by isolating lineage negative (Lin-),
      Sca-1-positive (Sca-1+) cells from normal mouse bone marrow. RhTGF-beta inhibited
      90% of colony formation stimulated by rrSCF plus rmIL-3 in agar culture of the
      Sca-1+ cells. RhTGF-beta also inhibited colony formation in agar culture of post
      FU human bone marrow cells. The synergistic increase in colony formation obtained
      with recombinant human SCF (rhSCF) plus rhGM-CSF and rhSCF plus rhIL-3 was
      inhibited by rhTGF-beta (approx. 60% and 87% inhibition, respectively). RhTGF
      beta also totally inhibited the erythroid colony formation stimulated by rhSCF
      plus recombinant human erythropoietin (rhEpo). These data demonstrate that TGF
      beta inhibits SCF-stimulated colony formation of mouse and human BM. This
      inhibition on progenitor cells appears to be a direct action of TGF-beta and is
      consistent with the target cells of SCF being more primitive progenitors than the
      CFCs stimulated by the CSFs alone.

PMID- 1372032
TI  - [Field trial for the early detection of patients with ovarian cancer-
      discrimination of ovarian cancer patients by the statistical analysis using
      Mahalanobis' generalized distance].
AB  - Six tumor-associated antigens, cancer antigen 125 (CA125), tissue polypeptide
      antigen (TPA), ferritin (Fr), carcinoembryonic antigen (CEA), alpha fetoprotein
      (AFP), and sialyl Lex-i (SLX) were measured simultaneously for the early
      detection of ovarian cancer. To decrease the number of both false positive and
      false negative cases in the combination assay, statistical discrimination
      analysis employing the serum values for appropriate tumor markers has been
      studied with respect to ovarian cancer by the method of Mahalanobis' generalized
      distance. The new "ovarian cancer screening test" designed by us has been used in
      Shizuoka Prefecture since 1988, and 23,307 serum samples have been analyzed. One
      hundred twenty-seven of 165 ovarian cancer patients were suspected as having
      cancer by such clinical procedures as pelvic examination and/or ultrasonography,
      while in 150 patients cancer was detected by the statistical discrimination
      method. Thirty-one of 38 patients with ovarian cancer overlooked by the clinical
      procedures could be found by the statistical method. We conclude that clinical
      procedures and the statistical method can be complementary in detecting patients
      with this malignancy.

PMID- 1372033
TI  - [Analysis of the expression of the antigen recognized by monoclonal antibody MSN
      1 in endometrial hyperplasia which progressed to endometrial cancer].

PMID- 1372034
TI  - [A case of ovarian mixed mesodermal tumor].

PMID- 1372035
TI  - Beta 2 microglobulin on the envelope of urinary cytomegalovirus is not associated
      with host class I human leukocyte antigen alpha chain.
AB  - Previous studies have shown that beta 2 microglobulin (beta 2m) is associated
      with glycoproteins present on the envelope of urinary human cytomegalovirus
      (CMV). beta 2m is non-covalently associated with the alpha chain of human
      leukocyte antigen (HLA) class I antigens and therefore it was of interest to
      determine whether the class I alpha chain is also associated with the beta 2m-CMV
      complex. Using a panel of monoclonal antibodies recognizing different
      conformational determinants on the HLA class I heterodimer or free beta 2m, we
      have shown that beta 2m but not the alpha chain of HLA class I could be
      immunoprecipitated from 125I-surface-labelled virions purified directly from
      urine. We therefore conclude that host class I HLA alpha chains are not
      associated with beta 2m on the envelope of urinary CMV.

PMID- 1372036
TI  - Location of antigenic sites defined by neutralizing monoclonal antibodies on the
      S1 avian infectious bronchitis virus glycopolypeptide.
AB  - Neutralizing monoclonal antibodies directed against five antigenic sites on the
      spike (S) S1 glycopolypeptide of avian infectious bronchitis virus (IBV) were
      used to select neutralization-resistant variants of the virus. By comparing the
      nucleotide sequence of such variants with the sequence of the IBV parent strain,
      we located five antigenic sites on the amino acid sequence of the S1
      glycopolypeptide. The variants had mutations within three regions corresponding
      to amino acid residues 24 to 61, 132 to 149 and 291 to 398 of the S1
      glycopolypeptide. The location of three overlapping antigenic sites on the IBV
      spike protein was similar to the location of antigenic sites on the spike protein
      of other coronaviruses.

PMID- 1372037
TI  - Poliovirus antigenic hybrids simultaneously expressing antigenic determinants
      from all three serotypes.
AB  - We have constructed six hybrid polioviruses (PVs) modified to express PV type 2
      and type 3 antigenic determinants on a PV type 1 (Mahoney) capsid. The hybrids
      were modified in neutralizing antigenic site (NAg) I and/or NAgII. They were
      viable, but impaired for growth in comparison to PV1 (Mahoney). Some hybrids
      modified to express type 2 and type 3 NAgI determinants simultaneously displayed
      some type 2 but no type 3 antigenicity (in addition to type 1 antigenicity
      associated with other antigenic sites). Hybrids modified to express a type 2 NAgI
      determinant and a type 3 NAgII determinant, or vice versa, displayed antigenic
      characteristics of all three serotypes, although expression of the modified NAgII
      determinant was weak. We conclude that it is possible to construct a viable
      hybrid PV simultaneously modified in NAgI and NAgII which expresses antigenic
      determinants of all three serotypes.

PMID- 1372038
TI  - Construction of solid matrix-antibody-antigen complexes containing simian
      immunodeficiency virus p27 using tag-specific monoclonal antibody and tag-linked
      antigen.
AB  - We have previously shown that immunization with solid matrix-antigen-antibody
      (SMAA) complexes induces both vigorous humoral and cell-mediated immune responses
      and have suggested that this method of vaccination may be developed for use in
      humans, and potentially as a vaccine against AIDS. Here we demonstrate that a
      small oligopeptide can act as a tag for the construction of SMAA complexes using
      a tag-specific monoclonal antibody and tag-linked antigens. We show that a 14
      amino acid oligopeptide, present in the phospho (P) and V proteins of simian
      virus 5 (SV5), retains its antigenicity when attached to the C terminus of three
      'foreign' proteins [p27 and gp110 of simian immunodeficiency virus (SIV) and
      glutathione S-transferase] such that these proteins can be incorporated into SMAA
      complexes using a monoclonal antibody (MAb) that was originally raised against
      the native SV5 P and V proteins. Mice were immunized with SMAA complexes
      containing recombinant p27-TAG and MAbs have been isolated that recognized native
      SIV p27. The significance of these results in terms of the development of SMAA
      complexes as human vaccines is discussed.

PMID- 1372039
TI  - Sulphate polyanions prolong the incubation period of scrapie-infected hamsters.
AB  - The effect of the organic sulphated polyanions, pentosan sulphate (SP54), dextran
      sulphate 500 (DS500) and suramin, have been tested on golden Syrian hamsters
      infected with the 263K strain of scrapie by the intraperitoneal (i.p.) or the
      intracerebral route. SP54 had the greatest effect in prolonging the incubation
      period of the disease when administered within 2 h of the i.p. inoculum. The same
      amount of SP54 given 24 h after scrapie inoculation had a potent effect in some
      animals and no effect in others. This result suggests that SP54 inhibits the
      uptake of the scrapie agent into the nerve endings and/or carrier cells at the
      site of the inoculum, i.e. the peritoneum, and that this event occurs in about 24
      h. DS500 had a similar although less potent effect (22.4 days delay during the
      incubation period) than SP54 (54.4 days) when administered within 2 h of scrapie
      injection by the i.p. route, and suramin had only a minimal effect (10 days).
      This study suggests that treatment of scrapie and related spongiform
      encephalopathies of animals and man is possible only before the agent has reached
      the clinical target areas of the brain.

PMID- 1372041
TI  - Down-regulation of vesicular stomatitis virus transcription by the matrix protein
      of influenza virus.
AB  - The matrix (M1) protein isolated from influenza A/WSN/33 virus, when
      reconstituted with ribonucleoprotein (RNP) cores of vesicular stomatitis virus
      (VSV), resulted in inhibition of VSV transcription in vitro. The presence of
      endogenous wild-type (wt) or mutant (tsO23) VSV matrix (M) protein on RNP cores
      did not prevent down-regulation of VSV transcription by reconstituted influenza
      virus M1 protein. In fact, endogenous VSV wt M protein augmented transcription
      inhibition by M1 protein reconstituted with RNP/M protein cores, whereas mutant
      tsO23 M protein endogenous to RNP cores had no effect on down-regulation of VSV
      transcription by M1 protein. These data suggest that VSV M protein and influenza
      virus M1 protein recognize two different sites on RNP cores responsible for down
      regulation of VSV transcription. Monoclonal antibodies (MAbs) directed to epitope
      2 of M1 protein had been previously shown to reverse transcription inhibition by
      M1 protein on influenza virus RNP cores, but the same epitope 2-specific MAb had
      little effect on transcription inhibition by M1 protein reconstituted with VSV
      RNP cores. VSV M protein bears a striking resemblance biologically and
      genetically to the M1 protein, including, as shown here, their capacity to bind
      viral RNA. However, the VSV wt M protein exhibited no capacity to down-regulate
      transcription by influenza virus RNP cores. The significance of these studies is
      the identification on VSV RNP templates of at least two separate sites for
      recognition of protein factors that repress VSV transcription.

PMID- 1372040
TI  - Epitope mapping on fragments of beet necrotic yellow vein virus coat protein.
AB  - The location of five SDS-stable epitopes on the coat protein (CP) of beet
      necrotic yellow vein virus was determined by reacting Escherichia coli-expressed
      free CP, as well as fusion proteins (FP) containing fragments of the CP, with
      polyclonal and monoclonal antibodies on Western blots. Epitope 1, which has
      previously been found to be exposed on only one extremity of the virus particle,
      was located in the region between amino acids (aa) 1 and 7, i.e. on the N
      terminus of the CP. It was blocked when the N terminus of the CP was linked to a
      portion of the beta-galactosidase sequence in an FP. Epitope 3, which has
      previously been found to be exposed on the opposite extremity of the particle,
      was located in the region between aa 37 and 59. Epitope 4, which is exposed along
      the entire length of the particle, occurs on the C terminus of CP (aa 183 to
      188). Two previously unknown epitopes were identified in the regions between aa
      115 and 125 and 125 and 140, respectively. The former was located on the same
      extremity of the particle as epitope 3, the latter became accessible only after
      denaturation of the particle. Nothing is known about the probably non-adjacent aa
      sequences that participate in the formation of the two SDS-labile epitopes
      (epitopes 2 and 5) which are found on one extremity and along the entire length
      of the particle, respectively.

PMID- 1372042
TI  - Molecular cloning and development analysis of a new glutamate receptor subunit
      isoform in cerebellum.
AB  - The glutamate receptor gene GluR-4 is proposed to generate two spliced isoforms
      (Sommer et al., 1990). Screening a rat cerebellar cDNA library, we have now
      identified a third type of transcript derived from GluR-4 gene by differential
      RNA processing. This transcript encodes a protein with a "flop" module between
      transmembrane regions 3 and 4, but with a C-terminus segment of 36 amino acids
      different from the previously described GluR-4 flip/flop cDNAs. This subunit was
      therefore designated as GluR-4c flop. Transcripts synthesized in vitro from GluR
      4c cDNA form kainate/AMPA-activated channels when expressed in Xenopus oocytes.
      The current-voltage relationship for kainate-evoked responses in oocytes injected
      with GluR-4c showed strong inward rectification. The different transcripts
      derived from the GluR-4 gene were studied on Northern blots hybridized with
      either a cDNA probe or oligonucleotides specific for the GluR-4 flip/flop and C
      terminal domains. Three transcripts of 6.2, 4.2, and 3.0 kilobases (kb) derived
      from the GluR-4 gene were identified on Northern blots containing total RNA
      prepared from different brain regions, using a cDNA probe or an oligonucleotide
      corresponding to the N-terminal region common to all transcripts. These
      transcripts were much more abundant in the cerebellum than in other brain areas,
      and their levels increased during cerebellar development. The maximal increase
      was observed between postnatal days 1 and 20, an age corresponding to the
      division and maturation of granule neurons. The flip/flop and the C-terminal
      oligonucleotides hybridized to the two higher molecular weight transcripts but
      did not hybridize to the small RNA. Interestingly, using cerebellar cells that
      were cultured for up to 12 d, we observed that the three transcripts are present
      in granule neurons, but that astrocytes only express the 6.2 and the 4.2 kb
      transcripts. The 3.0 kb transcript accumulates in cerebellar granule cells during
      development in vitro. Furthermore, in situ hybridization histochemistry revealed
      that the GluR-4c transcripts are preferentially expressed in cerebellar granule
      cells and Bergmann glial cells, whereas the expression of GluR-4 flip mRNAs is
      restricted to Bergmann glial cells. Interestingly, we also show that granule
      cells already express GluR-4c in the premigratory zone of the external granular
      layer, indicating that intrinsic or highly localized cues induce GluR-4c
      expression before these cells reach their final position.

PMID- 1372043
TI  - Expression of tenascin in the developing and adult cerebellar cortex.
AB  - Since tenascin may influence neuronal cell development, we studied its expression
      pattern using immunocytochemistry, in situ hybridization, Northern blot analysis,
      and immunochemistry in the developing and adult mouse cerebellar cortex. Tenascin
      immunoreactivity was detectable in all layers of the developing cerebellar
      cortex. In the external granular layer, only the radially oriented processes of
      Golgi epithelial cells were immunoreactive, whereas the densely packed cell
      bodies were immunonegative. Tenascin was hardly detectable at contact sites
      between migrating granule cells and processes of Golgi epithelial cells. Axons of
      granule cells in the molecular layer were immunoreactive, whereas their cell
      bodies in the internal granular layer lacked detectable levels of tenascin. By in
      situ hybridization, only Golgi epithelial cells and astrocytes of the internal
      granular layer and prospective white matter, but not nerve cells, could be shown
      to synthesize detectable levels of tenascin mRNA in the developing mouse
      cerebellar cortex. Thus, tenascin in the cerebellar cortex seems to be a glia
      derived molecule that becomes adsorbed to neuronal surfaces in a topographically
      restricted pattern in situ. Levels of tenascin protein and mRNA decreased
      significantly with increasing age. In the adult, tenascin immunoreactivity was
      weak and mainly restricted to the molecular layer and tenascin mRNA was confined
      to Golgi epithelial cells, indicative for a functional heterogeneity in
      differentiated cerebellar astrocytes. Quantitative immunoblot analysis revealed
      that the 225 and 240 kDa components of tenascin were developmentally
      downregulated at a faster rate than the 190 and 200 kDa components, corresponding
      to the faster downregulation of the 8 kilobase (kb) mRNA species compared to the
      6 kb mRNA species as revealed by Northern blot analysis. These observations
      indicate a differentially regulated expression of the tenascin components. We
      hypothesize that glia-derived tenascin modifies the functional properties of
      nerve cell surfaces and that tenascin is involved in such different morphogenetic
      events as neurite growth and oligodendrocyte distribution.

PMID- 1372045
TI  - Increased GABAA receptor binding in superficial layers of cingulate cortex in
      schizophrenics.
AB  - Recent investigations of postmortem brain from schizophrenic patients have
      revealed reduced numbers of neurons in several different corticolimbic brain
      regions. In the prefrontal and anterior cingulate cortices, more specific
      decreases in the numbers of interneurons, but not pyramidal cells, have been
      reported to occur preferentially in layer II. Based on this latter finding, a
      loss of inhibitory basket cells leading to a compensatory upregulation of the
      GABAA receptor has been hypothesized to occur in schizophrenic patients and to be
      a contributory factor in the pathophysiology of this disorder. We now report the
      results of a high-resolution quantitation of GABAA receptor binding in anterior
      cingulate cortex of postmortem specimens from normal and schizophrenic cases. The
      results indicate a preferential increase in bicuculline-sensitive 3H-muscimol
      binding on neuronal cell bodies of layers II and III, but not layers V and VI, of
      the schizophrenic cases. There was no difference in the size of neurons in any of
      the layers examined when the control and schizophrenic groups were compared. The
      neuropil of layer I also showed significantly greater GABAA binding in
      schizophrenics. The differences seen in the schizophrenic group did not appear to
      be the result of exposure to antipsychotic medication because one patient who was
      medication naive and a second who had received minimal exposure to antipsychotic
      drugs also showed elevated GABAA receptor binding. Since information processing
      depends on corticocortical integration in outer layers I-III, a disturbance of
      inhibitory activity in these superficial layers of limbic cortex may contribute
      to the defective associative function seen in schizophrenia.

PMID- 1372044
TI  - An actin-associated protein present in the microtubule organizing center and the
      growth cones of PC-12 cells.
AB  - The pathfinding ability of the growth cone depends upon the integrity of a
      dynamic actin filament network. However, although a number of actin-binding
      proteins have been found in growth cones, it is not known how these proteins come
      to be concentrated there or how they might interact to produce these important
      actin filaments. In this report, an actin-associated protein recognized by the
      monoclonal antibody 2E4 is demonstrated to be present in PC-12 cells. In
      undifferentiated cells, this protein is present in an apparently inactive state
      in a perinuclear location that corresponds to that of the microtubule organizing
      center and not of the Golgi apparatus. Conversely, after NGF-induced
      differentiation, the antigen is found enriched in the neurite and growth cone and
      disappears from the perinuclear position. This disappearance is directly
      proportional to the length of the neurite. The antigen-antibody complex binds the
      ends of actin filaments in vitro in an ATP-sensitive manner, and the antibody
      stains the outermost edge of the actin filament ruffle in the leading edge of
      migrating fibroblasts. Hence, it is possibly involved in the membrane-associated
      polymerization of actin filaments such as that observed in growth cones.

PMID- 1372046
TI  - Hollow microspheres for use as a floating controlled drug delivery system in the
      stomach.
AB  - Hollow microspheres (microballoons), loaded with drug in their outer polymer
      shells, were prepared by a novel emulsion-solvent diffusion method. The
      ethanol:dichloromethane solution of drug (tranilast or ibuprofen) and an enteric
      acrylic polymer were poured into an agitated aqueous solution of polyvinyl
      alcohol that was thermally controlled at 40 degrees C. The gas phase generated in
      the dispersed polymer droplet by the evaporation of dichloromethane formed an
      internal cavity in the microsphere of the polymer with the drug. The drugs
      incorporated in the solidified shell of the polymer were found to be partially or
      completely amorphous. The flowability and packability of the resultant
      microballoons were much improved compared with the raw crystals of drug. The
      microballoons floated continuously over the surface of acidic dissolution media
      containing surfactant for greater than 12 h in vitro. The drug release behavior
      of the microballoons was characterized as an enteric property, and drug release
      rates were drastically reduced depending on the polymer concentration at pH 6.8.

PMID- 1372047
TI  - Modulation of human basophil histamine release by protein kinase C inhibitors
      differs with secretagogue and with inhibitor.
AB  - To assess possible involvement of protein kinase C (PKC) in human basophil
      degranulation, the present work compared effects of various purported PKC
      inhibitors on leukocyte histamine release triggered by different stimuli. The
      effects recorded varied with the inhibitor and the secretagogue used; moreover,
      with a given secretagogue, different inhibitors often displayed different
      activities. Thus, histamine release triggered by the PKC activator 4 beta-phorbol
      12-myristate 13-acetate was blocked by K252a, staurosporine and the purported
      specific PKC inhibitor Ro 31-7549, and reduced by calphostin C, H-7, TMB-8 and W
      7 but not affected by polymyxin B; it was augmented by 2.1 microM palmitoyl
      carnitine. The leukocyte response induced by another putative activator of PKC,
      1,2-isopropylidene-3-decanoyl-sn-glycerol, was also enhanced by 2.1 microM
      palmitoyl carnitine, slightly increased by staurosporine, TMB-8 and W-7 but not
      affected by calphostin C, H-7, K252a or Ro 31-7549, whereas the hyperosmolar
      mannitol-induced response was reduced by H-7, calphostin C, TMB-8 and W-7 and
      slightly augmented by staurosporine. Anti-IgE-induced histamine release was
      blocked by staurosporine and K252a and reduced by calphostin C, sphingosine, TMB
      8 and W-7 but not affected by H-7, polymyxin B or retinal. It was enhanced by Ro
      31-7549. In contrast, leukocyte histamine release induced by calcium ionophore
      A23187 or by ionomycin was blocked by retinal, TMB-8 and W-7 and reduced by
      calphostin C and palmitoyl carnitine but enhanced by H-7, staurosporine and
      polymyxin B; K252a and Ro 31-7549 did not affect such responses. Formyl-methionyl
      leucyl-phenylalanine-triggered histamine release was barely affected by any agent
      used. Thus, the specific PKC inhibitor Ro 31-7549 selectively blocked 4 beta
      phorbol 12-myristate 13-acetate-triggered leukocyte histamine release. These
      results imply that examined secretagogues trigger human leukocyte histamine
      release through partly separate pathways probably involving different kinase
      activities (PKC isozymes?). Moreover, the distinct effect patterns recorded for
      most purported PKC inhibitors imply a functional selectivity between these
      compounds.

PMID- 1372049
TI  - alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor antagonists
      in the nucleus accumbens and ventral pallidum decrease the hypermotility response
      to psychostimulant drugs.
AB  - The purpose of this study was to determine the role of alpha-amino-3-hydroxy- 5
      methylisoxazole-4-propionate (AMPA)/kainate excitatory amino acid receptors in
      the nucleus accumbens and the ventral pallidum in the hypermotility responses to
      amphetamine, caffeine and scopolamine. To accomplish this, we determined the
      effects of intracranial injections of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and
      gamma-D-glutamylaminomethyl-sulfonate (GAMS), which inhibit the responses to
      AMPA, quisqualate and kainate in electrophysiological and behavioral studies. The
      bilateral administration of either DNQX (1 micrograms/0.5 microliters) or GAMS (5
      micrograms/0.5 microliters) into the nucleus accumbens inhibited the locomotor
      stimulation produced by amphetamine (0.5 mg/kg s.c.) but not by caffeine (20
      mg/kg s.c.) or scopolamine (0.5 mg/kg s.c.). However, the bilateral
      administration of either of the two antagonists into the ventral pallidum
      inhibited the response to all three stimulants. The administration of 6-amino-7
      fluroquinoxaline-2,3-dione, a chemical analog of DNQX that does not bind to AMPA
      receptors, into either the nucleus accumbens or the ventral pallidum did not
      inhibit the locomotor stimulation produced by amphetamine. Neither DNQX nor GAMS
      injected into either the nucleus accumbens or the ventral pallidum produced
      significant changes in the locomotor activity of animals not injected with the
      stimulants. These results suggest that activation of AMPA/kainate receptors in
      the nucleus accumbens is important in the stimulation of locomotion produced by
      amphetamine, whereas activation of these receptors in the ventral pallidum is
      involved in the hypermotility response to all three central nervous system
      stimulants.

PMID- 1372048
TI  - Amplification of alpha adrenergic vasoconstriction in canine isolated mesenteric
      artery and vein.
AB  - The interactions between UK-14304 and other vasoconstrictor agents were
      investigated using isolated canine mesenteric vascular rings mounted in tissue
      baths for the measurement of isometric contraction. In the mesenteric artery,
      exposure to UK-14304 caused a small contraction, producing 8% of the KCl maximal
      response. In the presence of either 20 mM KCl or 10(-9) M endothelin-1, which had
      small contractile effects, UK-14304 produced a biphasic concentration-response
      curve; 10(-7) M rauwolscine inhibited the responses to low concentrations of UK
      14304 and 10(-7) M prazosin blocked the responses to high concentrations of UK
      14304. In the presence of 10(-8) M Bay K 8644, UK-14304 elicited a monophasic
      concentration-dependent contraction that was antagonized by 10(-7) M prazosin,
      not by 10(-7) M rauwolscine. In the mesenteric vein, UK-14304 elicited
      concentration-dependent contractions, producing 63% of the KCl maximal response.
      The lower part of the biphasic concentration-response curve was inhibited by 10(
      7) M rauwolscine and the upper part of the curve was antagonized by 10(-7) M
      prazosin. The presence in the medium of 20 mM KCl, 10(-11) M endothelin-1 or 10(
      9) M Bay K 8644, which increased resting tension less than 10% of the KCl maximal
      response, markedly enhanced the responses to UK-14304 primarily at concentrations
      lower than 10(-6) M. The enhancement of responses were prazosin (10(-7) M)
      resistant and rauwolscine (10(-7) M)-sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372050
TI  - Dipeptidyl(amino)peptidase IV and aminopeptidase M metabolize circulating
      substance P in vivo.
AB  - Recent studies have demonstrated that Fischer-344 rats from Japanese Charles
      River Inc. specifically lack dipeptidyl(amino)peptidase IV (DAP IV-negative; EC
      3.4.14.5), whereas Fischer-344 rats from sources within the United States (DAP IV
      positive) possess normal DAP IV activity. In the present study, plasma from DAP
      IV-positive rats metabolized substance P (SP) (5.37 +/- 0.25 nmol/min/ml) via the
      actions of angiotensin-converting enzyme (EC 3.4.15.1) (1.86 +/- 0.50
      nmol/min/ml) and DAP IV (2.56 +/- 0.42 nmol/min/ml). DAP IV sequentially
      converted SP to SP[3-11] and SP[5-11]. The SP[5-11] metabolite was then rapidly
      hydrolyzed by plasma aminopeptidase M (AmM; EC 3.4.11.2) (36.2 +/- 4.2
      nmol/min/ml). In contrast, SP metabolism by plasma from DAP IV-negative rats was
      less than half that of control animals (2.14 +/- 0.06 nmol/min/ml), due to a
      complete lack of DAP IV hydrolysis. The absence of DAP IV was not associated with
      any differences in angiotensin-converting enzyme-mediated hydrolysis of SP (1.45
      +/- 0.11 nmol/min/ml) or AmM-mediated hydrolysis of SP[5-11] (37.1 +/- 0.9
      nmol/min/ml). Consistent with this deficiency in SP metabolism, SP was more
      potent in vivo in stimulating salivary secretion in DAP IV-negative rats compared
      to DAP IV-positive animals. Potentiation was specific in that SP[5-11], an SP
      fragment resistant to DAP IV, was equipotent in DAP IV-negative and positive
      animals. SP[5-11]-induced salivary secretion was potentiated in both strains when
      AmM-mediated hydrolysis was inhibited by amastatin (20 nmol/min, i.v.). These
      data provide direct evidence for a significant role for DAP IV and AmM in the in
      vivo processing of SP and active SP metabolites.

PMID- 1372051
TI  - The effects of FK-506, a novel and potent immunosuppressant, upon murine
      Coxsackievirus B3 myocarditis.
AB  - To test the therapeutic efficacy of immunosuppression with FK-506 upon
      coxsackievirus B3 myocarditis, C3H/He mice were inoculated with coxsackievirus
      B3, and the effects of FK-506 were compared to those of cyclosporine. FK-506 (2.5
      mg/kg/day) or cyclosporine (25 mg/kg/day) was administered s.c. daily on days 0
      to 14 (experiment I) and on days 14 to 28 (experiment II). In experiment I, the
      survival rate of the FK-506 or cyclosporine-treated group was significantly lower
      compared with that of the untreated, control group. However, the score of
      myocardial cellular infiltration in both treated groups was lower compared to the
      control. On day 14, myocardial virus was not detected in the control group, but
      was present in both treated groups. Serum neutralizing antibody titers on day 14
      in FK-506 group were lower than in the control group. In experiment II, survival
      rate did not differ significantly among the three groups. Serum-neutralizing
      antibody titers on day 21 in FK-506 group were lower than in the control.
      Histologically, marked cellular depletion in the thymus and spleen was evident in
      FK-506 groups; in cyclosporine groups, it was only evident in the thymus. Thus,
      FK-506 induced immunosuppression in coxsackievirus B3 myocarditis, associated
      with a high mortality, notwithstanding the reduction of myocardial cellular
      infiltration in the acute stage when immune mechanisms play a role in the
      pathogenesis of the disease. With respect to the dosage, the immunosuppressive
      action of FK-506 in vivo is at least 10-fold stronger compared to that of
      cyclosporine.

PMID- 1372053
TI  - Stat Bite. Impact of combination chemotherapy for advanced testicular cancer.

PMID- 1372052
TI  - Bay K-8644 in different solvents acts as a transient calcium channel antagonist
      and a long-lasting calcium channel agonist.
AB  - This report describes the effect of Bay K-8644 dissolved in various solvents on
      two types of calcium channel currents in neuroblastoma cells. Transient calcium
      channel (T channel) currents were not affected by Bay K-8644 dissolved in ethanol
      (EtOH) or polyethylene glycol (PEG). However, at the same concentration of 0.6
      microM, Bay K-8644 dissolved in dimethylsulfoxide (DMSO) (Bay K-8644/DMSO)
      decreased the T channel current by 50%. The concentration of all three solvents
      in the bath was fixed at 0.3% to reach different final concentrations of Bay K
      8644. At this fixed solvent concentration, the inhibitory effect of Bay K
      8644/DMSO on T channel currents was dose-dependent; the solvents alone did not
      have any effect on T channel currents; and DMSO pretreatment of cells did not
      render the T channel current sensitive to Bay K-8644 dissolved in EtOH or PEG.
      Bay K-8644/DMSO was dried using a flash evaporator and redissolved in EtOH or
      PEG. Dried Bay K-8644 that was redissolved in EtOH or PEG to achieve a final
      concentration of 0.6 microM inhibited T channel currents by 39 or 35%,
      respectively. Furthermore, Bay K-8644 (10 nM) increased L channel currents by 80%
      with DMSO, but only 30% with EtOH as the solvent. These results show that in
      neuroblastoma cells Bay K-8644/DMSO, within the concentration range examined, is
      a T channel antagonist and more effective L channel agonist than Bay K-8644
      dissolved in the two other solvents.

PMID- 1372054
TI  - [The sensitivity and specificity of various peroxidase stains--the difference
      between DAB and 3AC stainings].
AB  - FAB Cooperative Group has cited 3 or higher percentage in the peroxidase (PO)
      activity as one of criteria for the diagnosis of acute myeloid leukemia. We have
      previously reported in two cases of acute myelomonocytic leukemia (M4) that there
      was a great difference between 3,3'-diaminobenzidine (DAB) and 3-amino 9-ethyl
      carbazole (3AC) as substrates for PO reaction. In order to confirm the previous
      result, we extended the cases and compared the PO activities in blood films taken
      from several leukemic subjects, which were fixed with various kinds of fixatives,
      using DAB and 3AC as substrates. Their peroxidase activities were also determined
      through electron microscopy (EM-PO). There were no differences among fixatives
      and substrates in staining normal granulocytic cells (neutrophils and monocytes)
      and cells in 13 cases of leukemia, except for two cases, one with M4 and the
      other with relapse of M2. These showed the highest PO activity with 3AC staining
      and 10% formaldehyde acetone buffer for fixation. Besides, all types manifested
      the highest positivity in EM-PO, except for the relapse of M2 that showed a
      higher positivity in the peroxidase stain by 3AC staining, 10% formaldehyde
      acetone buffer fixation than the EM-PO. Unlike other leukemic blasts PO reaction
      products of blast cells of the two cases showed a scattered distribution of
      microscopic granules. These findings suggested the difference, which was seen in
      the previous reports, of the PO stain between two substrates might be due not
      only to sensitivity for staining but to the presence of some heterogeneity such
      as isoenzyme in the myeloperoxidase.

PMID- 1372055
TI  - Surface immunoglobulin density in the differential diagnosis of B-cell chronic
      lymphocytic leukemia and leukemic immunocytoma.
AB  - Using flow cytometry peripheral blood samples of 37 consecutive patients with B
      cell chronic lymphocytic leukemia (B-CLL) and 17 consecutive patients with
      leukemic immunocytoma (IC) were studied in order to determine quantitative
      differences in the surface immunoglobulin (slg) density. In 8/37 (21.6%) cases of
      B-CLL and 1/17 (5.9%) cases of IC slg staining remained in the control level.
      Analysis of slg-positive cases demonstrated a close association between the
      amount of slg and diagnosis: per case the mean calculated fluorescence intensity
      for IC lymphocytes was 209.7 arbitrary linear intensity units (IU) (median:
      156.4, standard error of the mean (SEM): 53.7) and for B-CLL lymphocytes 10.8 IU
      (median: 7.3, SEM: 1.1; p less than 0.0001). Altogether, 94.6% of all B-CLL
      patients and 76.5% of all IC patients were correctly classified when a cut-off
      point was fixed at a mean fluorescence intensity value of 20.0 IU. The percentage
      of leukemic cells as characterized by CD19 and HLA-DR reactivity was
      significantly lower in cases of IC (p less than 0.03 and p less than 0.01,
      respectively). In both entities disease progression occurred more frequently in
      advanced stages (II-IV) according to the Rai classification (p less than 0.01).
      In progressive disease rather than in stable disease circulating T lymphocytes
      were shown to express decreased amounts of surface CD3 antigen (p less than
      0.02). We conclude that the quantitative assessment of surface antigens in
      addition to their qualitative characterization provides accurate information. In
      particular, the diagnostic discrimination between B-CLL and IC may be improved by
      determining the lymphocytes' slg amount.

PMID- 1372056
TI  - Neoplastic basophil/mast cell precursors from chronic myelogenous leukemia
      display heterogeneous responses for a hematopoietic factor.
AB  - The response of neoplastic basophil/mast cell precursors to various hematopoietic
      factors was examined. Blastic or promyelocytic immature cells were obtained from
      six patients in basophilic crisis of chronic myelogenous leukemia. In all cases,
      after 14 days suspension culture more then 90% of the cells had basophilic
      features. 3H-thymidine uptake was markedly increased by the addition of GM-CSF in
      two cases, G-CSF in one, and IL-3 in two. In clonogenic cell assays, numerous
      colony formations were obtained when using the same growth factors as in the 3H
      thymidine uptake assay. In addition, IL-3 induced colony formation in one case,
      despite a lack of thymidine uptake IL-4 had a synergistic effect on colony
      formation with IL-3 in one other case. None of the factors used showed any effect
      on differentiation. These findings indicate that the proliferation of neoplastic
      basophil/mast cell precursors may be regulated by various growth factors but
      response patterns are divergent.

PMID- 1372057
TI  - Sustained, substantially increased concentration of prostate-specific antigen in
      the absence of prostatic malignant disease: an unusual clinical scenario.
AB  - A 60-year-old man had a persistent, marked increase in the serum concentration of
      prostate-specific antigen (more than 20 times the upper limit of the reference
      range) and no identifiable prostatic malignant involvement. To our knowledge,
      this is the first such case reported in the literature. Possible explanations for
      this increased value are described, and nonmalignant conditions that can increase
      serum concentrations of prostate-specific antigen are reviewed.

PMID- 1372058
TI  - Neurofilament epitopes in thymoma and antiaxonal autoantibodies in myasthenia
      gravis.
AB  - Expression by neoplastic thymic epithelial cells of acetylcholine-receptor (AChR)
      epitopes is associated with the presence of AChR autoantibodies and the
      development of myasthenia gravis. We studied thymic tumours from patients with
      and without myasthenia gravis for the expression of neurofilament epitopes by
      immunohistochemistry with four monoclonal antibodies. There was very little
      antibody binding in control samples (healthy thymus, or thymitis) or in medullary
      and mixed thymomas, but neurofilament epitopes were strongly expressed in all
      cortical thymomas and thymic carcinomas. In addition, the frequency of serum
      autoantibodies against axons was significantly higher among myasthenic patients
      with thymic epithelial tumours than among age-matched controls (7/10 vs 3/50; p
      less than 0.01).

PMID- 1372059
TI  - Neoadjuvant chemotherapy in multiple synchronous head and neck and esophagus
      squamous cell carcinomas.
AB  - A consecutive series of 22 patients with multiple synchronous squamous cell
      carcinomas of the upper aerodigestive tract was retrospectively reviewed. These
      patients were treated initially with cis-platinum combination chemotherapy before
      definitive locoregional therapy (surgery and/or radiation therapy). Sixteen of 21
      patients had simultaneous head and neck and esophageal primaries, 3 patients had
      multiple synchronous head and neck primaries, 2 patients had head and neck (HN)
      and a bronchial epidermoid cancer, and 1 patient had simultaneous esophageal and
      bronchial carcinomas of epidermoid lineage. Sixteen (77%) of the 21 patients
      responded to chemotherapy in all the tumor sites evaluated, and a clinically
      complete response was obtained in 6 (29%). After definitive locoregional
      treatment, the complete local control rate was 68%, with 34 complete responses
      for 50 primary tumor sites in 21 patients. Twelve patients were free of disease
      after locoregional treatment. Six patients are still alive 27 to 57 months after
      complementary definitive locoregional treatment and a minimum follow-up of 27
      months. Median survival for the overall group is 17 months. The response to
      chemotherapy is remarkable, which may be due to the small tumoral volume present
      in many of the cases (T1 to T2). Nevertheless, the present report stresses the
      importance of an aggressive combined therapeutic approach in this difficult
      clinical situation.

PMID- 1372060
TI  - Recent developments in the understanding of bradykinin receptors.
AB  - The dramatic activities of bradykinin and related peptides as mediators of pain,
      inflammation and hypotension have been intensely studied for several decades.
      More recently, the involvement of bradykinin in regulation of ion transport by
      epithelia, hormone release from endocrine organs, energy metabolism, tissue
      growth, and leukocyte activation have become topics of study. Kininogen
      precursors, synthetic kallikreins, and degradative kininases have been
      characterized in detail with regard to catalytic mechanisms, physical structure
      and gene regulation; however, the actual receptors for bradykinin are still only
      poorly understood. This situation is caused by the lack of availability of
      potent, specific receptor antagonists. However, specific bradykinin receptor
      antagonists became available in 1985, and several very potent classes of agents
      are now available; also, the first bradykinin receptor has been cloned.

PMID- 1372061
TI  - Central-type benzodiazepines modulate GABAA receptor chloride channels in
      cultured pituitary melanotrophs.
AB  - The effects of gamma-aminobutyric acid (GABA) and benzodiazepines on the
      electrical activity of cultured frog melanotrophs were studied using the patch
      clamp technique. In the cell-attached configuration, the exposure to GABA caused
      a blockage of the spontaneous firing. In the whole-cell configuration, with
      physiological chloride concentrations, GABA evoked a hyperpolarization associated
      with a decrease of membrane resistance, generating an inward chloride current.
      Clonazepam, a central-type benzodiazepine agonist, potentiated the GABA-induced
      current and the resulting hyperpolarization. In addition, the benzodiazepine
      inverse agonist Ro 19-4603 totally abolished GABA-induced hyperpolarizing
      chloride current. Since the pars intermedia of the frog pituitary is composed of
      a 'pure' population of endocrine cells enriched with GABAA receptors, our results
      indicate that these cells represent a valuable model in which to investigate the
      electrophysiological effects of ligands for the GABAA benzodiazepine receptor
      complex.

PMID- 1372062
TI  - Elevation of cyclic AMP levels in cell lines derived from latently infectable
      sensory neurons increases their permissivity for herpes virus infection by
      activating the viral immediate-early 1 gene promoter.
AB  - Immortalized cell lines derived from sensory neurons are relatively non
      permissive for lytic infection with herpes simplex virus (HSV) and fail to
      transcribe the viral immediate-early genes following infection. Treatment of
      these cells with agents which raise the intra-cellular level of cyclic AMP
      results in increased activity of the IE1 gene which contains a cyclic AMP
      response element within its promoter and produces a consequent increase in
      permissivity for HSV infection. The significance of these effects for the
      regulation of HSV infection of neuronal cells are discussed in the light of the
      finding that cyclic AMP treatment can reactivate latent HSV infections.

PMID- 1372063
TI  - De novo production of alpha 2-macroglobulin in cultured astroglia from rat brain.
AB  - Previous studies from our laboratory demonstrated that alpha 2-macroglobulin
      (alpha 2M) is one of the neurite-promoting factors in the conditioned medium of
      astroglia. In the present study, we further examined the de novo production of
      alpha 2M in cultured astroglia by determining the expression of alpha 2M mRNA,
      and the biosynthesis of [35S]methionine-labeled alpha 2M protein. We analyzed the
      mRNA of cultured astroglia by differential hybridization using specific probes to
      alpha 2M and its homologous protein, alpha 1-inhibitor 3 (alpha 1I3), after
      amplification of reverse-transcribed cDNA with the polymerase chain reaction. The
      result clearly showed that only alpha 2M mRNA is expressed in cultured astroglia.
      Northern blotting analysis revealed that alpha 2M mRNA is expressed mainly in the
      astroglia and is not detected in neurons, microglia and meningeal fibroblasts.
      Furthermore, the biosynthesis of alpha 2M protein in the astroglia was confirmed
      by an immunoprecipitation experiment after labeling of each type of cell with
      [35S]methionine. It was concluded that alpha 2M is produced in the cultured
      astroglia which is the major source of alpha 2M production among various types of
      cells in rat brain.

PMID- 1372064
TI  - Changes in relative levels of specific brain mRNA species associated with
      schizophrenia and depression.
AB  - Total cellular polyadenylated RNA (poly(A)+ RNA, mRNA) was prepared after
      guanidinium thiocyanate extraction of frozen brain tissue from age-matched
      controls and patients suffering from schizophrenia and unipolar depression. These
      mRNA populations were analysed by in vitro translation followed by two
      dimensional gel analysis. Data were obtained from fluorograms derived from 10
      different schizophrenic patients, 10 different controls and 5 different
      depressive patients. The relative concentrations of mRNA species coding for 4
      translation products (33 kDa, pI 5.8; 26 kDa, pI 5.8; 35 kDa, pI 7.1; 23 kDa, pI
      6.1) were significantly reduced in schizophrenia compared to controls when
      determined by computerised image analysis of the fluorograms. In the case of
      depression, the relative concentrations of mRNA species coding for 6 translation
      products were significantly altered, 4 being increased (38 kDa, pI 6.2, 17 kDa,
      pI 5.7, 35 kDa, pI 7.1; 23 kDa, pI 6.1) and two decreased (34 kDa, pI 6.2; 33
      kDa, pI 5.8). Three translation products were altered in both schizophrenia and
      depression, one (33 kDa, pI 5.8) being altered according to the same trend, a
      decrease relative to controls, but two (35 kDa, pI 7.1; 23 kDa, pI 6.1) being
      altered differently in schizophrenia (reduced) and depression (increased). The
      effects of post mortem delay, mode of death and drug treatment on mRNA
      composition were also examined and found not to affect the levels of these
      translation products significantly. The significance of these changes will be
      discussed in relation to their relevance of biological mechanisms in the
      psychoses.

PMID- 1372065
TI  - Time course of enkephalin mRNA and peptides in cultured rat adrenal medulla.
AB  - Explantation of rat adrenal medullae to organ culture results in dramatic changes
      in enkephalins and catecholamines that are similar to the changes seen in vivo in
      response to denervation, which eliminates transsynaptic impulse activity. We have
      used rapid and sensitive solution hybridization methods to measure
      preproenkephalin (PPenk) mRNA and total cellular RNA in samples from rat tissues
      and adrenal medullary explants. The profiles of adrenal medullary PPenk mRNA,
      enkephalin-containing (EC) peptides, total cellular RNA and catecholamines
      [epinephrine (epi) and norepinephrine (norepi)] were measured during 14 days of
      organ culture. After 8 h in culture, total RNA had declined by 60%, epi and
      norepi declined 80 to 85% and EC peptides by 50% while the amount of PPenk mRNA
      per gland increased by 400%. Between 8 h and 14 days total RNA and catecholamine
      levels remained constant while PPenk mRNA increased to a peak of 85 +/- 10
      (S.E.M.) pg/gland at 2-4 days, a value that was 80 times greater than the zero
      time (preculture) values. EC peptide levels lagged behind the increase in PPenk
      mRNA and reached a peak of 25 +/- 4 (S.E.M.) pmol Met-enkephalin
      equivalents/gland at 4 days that was 80 times greater than zero time values. Both
      PPenk mRNA and EC peptides declined in parallel between 4 and 14 days. The ratio
      of the copies of proenkephalin (Penk) peptide to PPenk mRNA was estimated to be
      25,000 at the time of explantation and after 4 days in culture. From steady-state
      kinetics half-life estimates of 9.6 h for PPenk mRNA and 14.7 h for Penk peptide
      were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372066
TI  - Gene expression of the insulin-like growth factors and their receptors in
      cultured human retinal pigment epithelial cells.
AB  - Insulin-like growth factors I and II (IGF I and II) are polypeptides with both
      growth-promoting and insulin-like metabolic effects. Immunoreactive IGF I is
      present in the retina and both IGF I and II are present in vitreal fluid. The
      type I and type II IGF receptors are also localized within the neural retina. The
      presence of IGFs and IGF receptors within the eye suggests a possible growth
      promoting effect of IGFs on ocular tissues. IGF may enter the eye from the blood
      or, alternatively, arise from an ocular cell type which synthesizes and secretes
      IGF. IGF I and II mRNA synthesis in scleral cells and IGF I synthesis in rat
      retina suggests endogenous IGF production in the eye. We hypothesized that IGFs
      and IGF receptors are synthesized by one ocular cell type, the retinal pigment
      epithelium (RPE). As a first step in studying IGF production by the RPE, we
      analyzed expression of the IGF and IGF receptor genes by cultured human RPE
      cells. Using Northern analysis, RNase protection and reverse-transcriptase
      polymerase chain reaction (RT-PCR), we found that cultured RPE cells synthesize
      mRNA for IGF I and the type I and type II IGF receptors.

PMID- 1372067
TI  - Acute lithium treatment enhances neuropeptide Y gene expression in rat
      hippocampus.
AB  - It has been suggested that the therapeutic action of lithium in affective
      disorders may be due to its inhibition of signal transduction and second
      messenger synthesis, in particular of the phosphoinositide (PI) pathway. Yet,
      previous work in neuronal cell lines indicates that lithium has an enhancing
      effect on gene expression mediated by protein kinase C, which is activated by the
      PI pathway. In this report, we have analyzed the effect of lithium on two
      neuropeptide encoding genes that are regulated by second messenger systems;
      neuropeptide Y (NPY) and proenkephalin (Enk). We find that acute treatment with
      lithium, resulting in serum levels that are within the therapeutic range
      effective in patients with mood disorders, significantly enhances basal
      expression of the NPY gene in rat hippocampus. In contrast, no effect on Enk
      expression was detected. This selective effect in a limbic structure supports the
      hypothesis that gene expression may be an important target of lithium's
      therapeutic action.

PMID- 1372068
TI  - Changes in immediate early gene expression during postnatal development of cat
      cortex and cerebellum.
AB  - Postnatal brain development involves interactions between extracellular signals
      and preprogrammed genetic events. Immediate early genes (IEGs) are a group of
      genes that are induced by extracellular signals and their protein products alter
      transcription by binding regulatory elements in other genes. Using Northern and
      slot blot analysis of total RNA isolated from visual cortex, frontal cortex, and
      cerebellum of cats, we have determined the postnatal development patterns of mRNA
      expression for 5 of these genes, c-fos, erg-1, c-jun, jun-B, and c-myc. Each gene
      had a distinct developmental pattern of mRNA expression, and for a given gene,
      these patterns were often different in different brain structures. These results
      suggest that temporal changes in the combinatorial interaction of different IEGs
      during early postnatal life are important for normal brain development.

PMID- 1372069
TI  - Expression of the proto-oncogene c-fos in three-dimensional fetal brain cell
      cultures and the lack of correlation with maturation-inducing stimuli.
AB  - Previous work has shown that aggregating fetal brain cell cultures are able to
      attain a highly differentiated state, and that their development is greatly
      enhanced by growth and/or differentiation factors such as epidermal growth factor
      (EGF), basic fibroblast growth factor (bFGF), and the protein kinase C-activating
      tumor promoter mezerein. The present study shows that in these 3-dimensional
      cultures the peptide growth factors EGF and bFGF as well as mezerein are able to
      induce the expression of the proto-oncogene c-fos. This induction was rapid and
      transient, in good agreement with observations reported from a wide variety of
      cell types in vitro. The maximal levels of c-fos mRNA found after stimulation
      were low in immature cultures and increased greatly as maturation progressed. Of
      the three factors tested, mezerein was the most potent inducer of c-fos. In
      contrast to the peptide growth factors EGF and bFGF which were found to induce c
      fos only in glial cells, mezerein was stimulatory in glial cells as well as in
      neurons. A similar cell type specificity has been observed previously for the
      maturation-enhancing response in immature aggregate cultures. However, in the
      present study no correlation was found between the degree of c-fos induction and
      the extent of the maturation-enhancing stimulation. Immature cultures known to be
      most sensitive and responsive to these maturation-enhancing agents required
      relatively high doses of peptide growth factors for the induction of c-fos, and
      the maximal levels of c-fos mRNA elicited were much lower than those in
      differentiated cultures which did not show any long-term response to these
      stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372070
TI  - Characterization of two cDNAs encoding insulin-like growth factor 1 (IGF-1) in
      the human fetal brain.
AB  - Insulin-like growth factor 1 (IGF-1) regulates growth of the brain. In order to
      characterize the variant IGF-1 present in human fetal brain we have determined
      the cDNA sequence for human fetal brain IGF-1. Using PCR to amplify cDNA obtained
      from isolated human fetal brain mRNA, two cDNA sequences encoding precursor
      proteins which correspond to IGF-1a and IGF-1b were obtained. This is the first
      characterisation of IGF-1 and its IGF-1a and IGF-1b precursors in the nervous
      system.

PMID- 1372072
TI  - Chronic atropine administration up-regulates rat cortical muscarinic m1 receptor
      mRNA molecules: assessment with the RT/PCR.
AB  - The modulation of the rat cortical m1 muscarinic receptor mRNA was studied with a
      method of quantitation using the polymerase chain reaction after conversion to
      complementary DNA (cDNA) with AMV reverse transcriptase (RT/PCR). Primers
      specific to the C3 region of the m1 mRNA were employed. The y-intercepts from the
      linear regions of semilogarithmic plots of PCR product versus cycle number were
      used as measures of the levels of m1 muscarinic mRNA-measured relative to that of
      glyceraldehyde phosphate dehydrogenase (GAPDH) mRNA (the 'ratio' method).
      Alternatively, m1 mRNA in total cortical RNA samples was quantitated from the
      increase in product elicited by adding a known amount of exogenous m1 muscarinic
      cDNA sequence (the 'spiking' method). This allowed calculation of absolute level
      of m1 mRNA, which was 4.1 pg/micrograms total RNA. We measured the level of the
      rat cortical m1 mRNA after 1 week of chronic receptor blockade with atropine,
      showing upregulation of 154% by the GAPDH/m1 ratio method and 145% by the spiking
      method. That this transcriptional alteration was specific was indicated by the
      finding that the level of GAP-43 mRNA was not affected by atropine treatment.

PMID- 1372071
TI  - P0 gene expression in Schwann cells is modulated by an increase of cAMP which is
      dependent on the presence of axons.
AB  - The role of cAMP in the regulation of P0 gene expression was investigated in
      Schwann cells of normal, regenerated, and permanently transected rat sciatic
      nerve. Forskolin treatment of endoneurial segments of rat sciatic nerve resulted
      in increased cAMP and P0 mRNA levels in normal and regenerated nerves but not in
      permanently transected nerves, where axonal regeneration is prevented. This
      increase of cAMP and P0 mRNA occurred within 30 and 90 min, respectively. P0 mRNA
      levels in the endoneurial segment of the permanently transected nerve were not
      increased with dibutyryl cAMP. The Schwann cells of the permanently transected
      nerve, however, retained the ability to myelinate 15 embryonic day (E15) dorsal
      root ganglia (DRG) neuron and neurite networks cultured in vitro. P0 mRNA levels
      increased within 4 days in transected endoneurium segments cocultured with E15
      DRG neurons and neurites and further increased in 21 day myelinating cocultures.
      Although cAMP was not detectable in 4 day cocultures, it increased to detectable
      levels in 21 day cultures, suggesting that cAMP is involved in the myelinating
      process. These results indicate that the presence of the axon is required for the
      observed increase of cAMP and P0 mRNA levels and suggest that the increase of
      cAMP occurs within the axon which then presumably activates a different Schwann
      cell second messenger pathway to induce P0 gene expression.

PMID- 1372073
TI  - Identification and characterization of a large human brain gene whose expression
      is increased in Alzheimer disease.
AB  - A cDNA clone that was isolated from a human substantia innominata cDNA library is
      described. By Northern hybridization analysis, a 15.5 kilobase (kb) transcript
      was identified by this clone in RNA samples from several brain regions, but not
      in RNA samples from white matter, liver or placenta. Hybridization to human
      genomic DNA revealed a pattern indicative of a single copy gene. DNA sequence
      analysis showed 3.0 kb of 3' untranslated region with no significant open reading
      frame. An additional cDNA clone, representing a section of an alternate form of
      this transcript, was isolated that contained an additional 1.5 kb at the 3' end.
      Using a nuclease protection assay, the expression of this gene was found to be
      increased by 30% in Alzheimer disease temporal cortex RNA samples compared to
      temporal cortex RNA samples from normal controls, but to be at equivalent levels
      in Alzheimer disease, as compared to normal control, substantia innominata RNA
      samples. This assay also showed that this gene was expressed at 3.5-fold higher
      levels in normal substantia innominata than in normal cerebellum. In situ
      hybridization analysis showed that the transcript could be detected in cerebellar
      neurons.

PMID- 1372075
TI  - Characterization of the antigenic and adhesive properties of FaeG, the major
      subunit of K88 fimbriae.
AB  - The two K88 serotypes, K88ab and K88ac, differ in terms of antigenic and adhesive
      properties. The structural determinants of the serotype-specific epitopes and the
      identify of the amino acid residues involved in fimbriae-receptor interaction
      were studied by the construction and analysis of K88 hybrid proteins in which
      various parts of the K88ab and K88ac fimbrial subunit FaeG were exchanged, and by
      in vitro mutagenesis of non-conserved amino acid residues. Using a set of
      monoclonal antibodies, several regions or amino acid residues involved in the
      formation of serotype-specific antigenic determinants were located. The
      haemagglutinating activity of the hybrid and mutant proteins revealed several
      amino acid residues involved in the formation of the receptor binding site. A
      clear correlation was found between the receptor binding site and the serotype
      specific antigenic determinants.

PMID- 1372074
TI  - Isolation and characterization of a library of cDNA clones that are
      preferentially expressed in the embryonic telencephalon.
AB  - In order to isolate genes involved in development of the mammalian telencephalon
      we employed an efficient cDNA library procedure. By subtracting an adult mouse
      telencephalic cDNA library from an embryonic day 15 (E15) mouse telencephalic
      cDNA library we generated two subtracted libraries (ES1 and ES2). We estimate
      that ES1 contains between 200 and 600 different cDNA clones, which approximates
      the number of genes that are preferentially expressed in the E15 telencephalon,
      compared to the adult telencephalon. Northern analysis of 20 different cDNA
      clones shows that 14 of these are expressed at least 5-fold more in the E15
      telencephalon than the adult telencephalon. Limited sequencing of the 14
      differentially expressed clones reveals that 10 have no significant identity to
      sequences in GenBank and EMBL databases, whereas the other 4 have significant
      sequence identity to vimentin, histone 3.3, topoisomerase I and the B2 repeat
      element. In situ hybridization using one of the differentially expressed cDNAs,
      TES-1, demonstrates that it is transiently expressed in the anlage of the basal
      ganglia. In situ hybridization with another differentially expressed cDNA clone,
      TES-4, shows that it is specifically expressed in differentiating cells of the
      neural axis with a distinctive rostral-caudal temporal pattern. These findings,
      and the methods that we have developed, provide a framework for future
      investigations of the genetic control of telencephalon development.

PMID- 1372076
TI  - The impact of recent advances in diagnostic technology on the clinical
      presentation of phaeochromocytoma.
AB  - OBJECTIVE: To examine the impact of recent advances in diagnostic technology on
      the spectrum of clinical and biochemical features of patients presenting with a
      new diagnosis of phaeochromocytoma. DESIGN: A retrospective review of the
      clinical and biochemical features of patients diagnosed by our laboratory as
      having phaeochromocytoma within a 27-month period up to December, 1990.
      Noradrenaline, adrenaline and dihydroxyphenylglycol were assayed in 24-hour urine
      specimens (19 patients) or plasma (1 anuric patient) by gas chromatography/mass
      spectrometry. SETTING: A tertiary level chemical pathology department. PATIENTS:
      Twenty patients with a new diagnosis of phaeochromocytoma. RESULTS: The classic,
      episodic adrenergic symptoms traditionally associated with phaeochromocytoma were
      absent in 9 of the 20 patients (45%). "Atypical" phaeochromocytoma presented as a
      mass on computed tomography imaging (6 patients, 30%), "phaeochromocytoma crisis"
      (4 patients, 20%) or family screening (1 patient, 5%). Excessive adrenaline
      production was found in 11 patients (55%) and six (30%) had predominantly
      adrenaline-secreting tumours. The urinary noradrenaline:dihydroxyphenylglycol
      ratio was raised in all nine patients with predominantly noradrenaline-secreting
      tumours but was not raised in nine out of ten patients with adrenaline-secreting
      phaeochromocytoma. Adrenaline excretion was significantly correlated with tumour
      size (r = 0.8; P less than 0.05). CONCLUSIONS: Advances in diagnostic technology,
      particularly specific adrenaline assays and computed tomography, have made
      possible the early diagnosis of patients with phaeochromocytoma presenting in
      ways previously thought to be uncommon. All patients with adrenal masses noted
      incidentally on CT scan should be investigated for phaeochromocytoma. Adrenaline
      secreting tumours are common and both noradrenaline and adrenaline should be
      assayed in all patients investigated for phaeochromocytoma.

PMID- 1372077
TI  - Teaching palliative medicine.

PMID- 1372078
TI  - The development of hepatitis C antibody shortly after acute icteric non-A non-B
      hepatitis.
AB  - OBJECTIVE: To determine the relationship between the development of hepatitis C
      antibody (anti-HCV) and the clinical symptoms in acute hepatitis C. DESIGN:
      Retrospective analysis of sera from patients with acute non-A non-B hepatitis.
      SETTING AND PATIENTS: Patients admitted to Fairfield Hospital with the diagnosis
      of acute non-A non-B hepatitis between 1979 and 1989. Inclusion criteria included
      a typical clinical illness, accompanied by an alanine aminotransferase level of
      more than 2.5 times the upper limit of normal (normal, less than or equal to 40
      U/L) and negative serological test results for acute hepatitis A and B. MAIN
      OUTCOME MEASURE: Time to develop anti-HCV after the onset of symptoms in patients
      with acute hepatitis C. RESULTS: Seroconversion was demonstrated in 26 of the 128
      patients who fulfilled the inclusion criteria. In these patients, antibody was
      detected between one week and 32 weeks after the onset of dark urine; more than
      half the patients (54%) had seroconverted by four weeks and a third (34%)
      developed antibodies within two weeks. Of 20 patients who had sera collected
      within four weeks of the onset of dark urine, 14 (70%) had developed antibody.
      CONCLUSION: These results suggest that in patients with community-acquired
      hepatitis C, seroconversion occurs significantly earlier than is observed in
      patients who have been infected by blood transfusion. Sera taken shortly after
      the onset of symptomatic hepatitis C may be useful in the diagnosis of this
      condition.

PMID- 1372079
TI  - Who needs a hospice?
AB  - OBJECTIVE: Rapid evolution of palliative care programs in Australia over recent
      years has brought the role of traditional inpatient hospices under review. This
      study attempts to define the clinical characteristics of patients referred for
      inpatient palliative care. DESIGN: A retrospective chart survey was performed of
      432 consecutively referred patients. SETTING: The study was undertaken in a 60
      bed hospice providing intensive nursing and medical care to patients with
      terminal illness. OUTCOME MEASURES: Demographic characteristics, diagnosis,
      length of stay, outcome and use of analgesics are presented. Patients not using
      regular analgesia at admission were studied to determine their major symptom
      complexes and their use of medication. RESULTS: Public hospitals referred 67.6%
      of patients and 25% came from home. While 83.8% of patients died in hospice care,
      16.2% were discharged, usually to home or a nursing home. At admission, 16.9% of
      patients could walk unassisted, 20.6% were chair-bound and 62.5% were bed-bound.
      The median length of stay in the hospice was 16 days. Ambulant status, female
      sex, non-use of opioids and a diagnosis of brain or breast cancer were all
      associated with longer stay. At admission, 39.1% of patients were taking potent
      opioids regularly, 22.9% were taking mild analgesics and 38.0% were taking no
      regular analgesia. Of those taking no analgesia, cachexia (55.9%), confusion
      (35.4%), impaired conscious state (19.9%) and impaired motor neurological
      function (21.7%) were the major clinical problems. CONCLUSIONS: The data show
      that patients selected for hospice care were highly dependent, with major
      functional impairments and short life expectancy. The medical, social and
      economic implications of these findings are discussed.

PMID- 1372080
TI  - Palliative care in a general teaching hospital.

PMID- 1372081
TI  - Kupffer cells contain voltage-dependent calcium channels.
AB  - Kupffer cells, the resident hepatic macrophages, are activated by calcium, but
      conclusive evidence that they contain voltage-dependent calcium channels has not
      been presented previously. In this study, the cytosolic free calcium
      concentration ([Ca2+]i) of cultured Kupffer cells was measured with the
      fluorescent Ca2+ indicator fura-2. Partial replacement of extracellular Na+ by K+
      caused an increase in [Ca2+]i in a concentration-dependent manner (half-maximal
      effect at 81 mM K+), presumably due to membrane depolarization. At 65 mM K+,
      where there were minimal changes in [Ca2+]i, addition of the dihydropyridine-type
      calcium channel agonist BAY K 8644 (1 microM) caused a large increase in [Ca2+]i.
      Overall, the effect of BAY K 8644 (1 microM) was to shift the concentration
      response curve for K+ to the left (half-maximal effect at 61 mM K+). Under
      depolarizing conditions (65 mM K+), BAY K 8644 increased [Ca2+]i in a
      concentration-dependent manner (half-maximal effect at approximately 400 nM BAY K
      8644). Moreover, the dihydropyridine-type calcium channel blocker nitrendipine
      inhibited the BAY K 8644-induced increase in [Ca2+]i in a concentration-dependent
      manner (half-maximal inhibition with about 25 nM nitrendipine). When
      extracellular Ca2+ was omitted from the incubation medium, the increases in
      [Ca2+]i due to BAY K 8644 were prevented completely. In addition, an
      intracellular Ca2+ antagonist, 8-(N,N-diethylamino)-octyl-3,4,5
      trimethoxybenzoate hydrochloride (200 microM), did not inhibit the BAY K 8644
      sensitive, voltage-dependent increase in [Ca2+]i. Thus, these data collectively
      indicate that BAY K 8644 causes a transmembrane Ca2+ influx in Kupffer cells in a
      voltage-dependent manner, providing the first direct evidence that Kupffer cells
      contain L-type voltage-dependent Ca2+ channels.

PMID- 1372082
TI  - Membrane-permeable dideoxyuridine 5'-monophosphate analogue inhibits human
      immunodeficiency virus infection.
AB  - 2',3'-Dideoxyuridine (ddU) is ineffective at controlling human immunodeficiency
      virus type 1 (HIV-1) infection in human T cells, because it is not biotransformed
      to the active 5'-triphosphate. The metabolic block resides in the poor substrate
      affinity of ddU for cellular nucleoside kinases. This problem cannot be overcome
      by supplying the preformed nucleotides, because such compounds are unable to
      penetrate cells. To circumvent the requirement of ddU for enzymic
      phosphorylation, we have prepared bis(pivaloyloxymethyl) 2',3'-dideoxyuridine 5'
      monophosphate (piv2 ddUMP), as a potential membrane-permeable prodrug of ddUMP,
      and investigated its metabolism and anti-HIV activity in two human T cell lines,
      one with wild-type thymidine kinase activity (MT-4) and the other deficient in
      thymidine kinase activity (CEM-tk-). The 5'-mono-, di-, and triphosphates of ddU
      were formed in both cell lines after exposure to piv2-ddUMP. In contrast,
      phosphorylated metabolites were not observed in cells treated with ddU or ddUMP
      alone. piv2-ddUMP also reduced the cytopathic effects of HIV-1 in MT-4 cells
      (ED50, 4.75 microM) and inhibited virus production in culture fluid (ED50, 20
      microM). In addition, piv2-ddUMP protected CEM-tk- cells from HIV-1 infection, as
      demonstrated by inhibition of intracellular p24 antigen levels (ED50, 3 microM)
      and reverse transcriptase activity in culture medium (Ed50, 2.5 microM). Based on
      these findings, we propose that the "masked nucleotide" strategy may make
      available for development nucleoside analogues hitherto considered inactive
      because of failure to undergo biotransformation to the corresponding 5'
      monophosphates. Moreover, by circumventing metabolic dependency on nucleoside
      kinases, the strategy may overcome acquired resistance to nucleoside analogues
      caused by the loss or depletion of nucleoside kinases.

PMID- 1372083
TI  - In vitro selection and molecular characterization of human immunodeficiency virus
      1 resistant to non-nucleoside inhibitors of reverse transcriptase.
AB  - Several newly discovered potent and selective non-nucleoside inhibitors of human
      immunodeficiency virus-1 reverse transcriptase (RT) are undergoing evaluation in
      clinical trials. We studied the potential for development of viral resistance to
      one of the prototype compounds, BI-RG-587, a dipyridodiazepinone derivative.
      Human immunodeficiency virus-1 resistant to BI-RG-587 emerged after only one
      cycle of in vitro infection in the presence of the drug. Resistant virus was
      cross-resistant to the non-nucleoside tetrahydroimidazo[4,5,1
      jk][1,4]benzodiazepin-2(1H)-thione derivative R82150 but remained susceptible to
      2',3'-dideoxynucleosides and phosphonoformate. Both native (virion-associated)
      and recombinant RT derived from resistant virus were insensitive to BI-RG-587 and
      R82150. Nucleotide sequence analysis of multiple drug-resistant and -sensitive
      recombinant RT clones identified a single predicted amino acid change common to
      all resistant clones (tyrosine-181----cysteine). These studies suggest that the
      viral resistance to non-nucleoside RT inhibitors may develop in vivo. This
      possibility should be carefully monitored in clinical trials of these compounds.

PMID- 1372084
TI  - In vitro and in vivo receptor binding and effects on monoamine turnover in rat
      brain regions of the novel antipsychotics risperidone and ocaperidone.
AB  - Risperidone and ocaperidone are new benzisoxazol antipsychotics with particularly
      beneficial effects in schizophrenia. We report a comprehensive study on the in
      vitro and in vivo receptor binding profile of the new compounds, compared with
      haloperidol, and on the drug effects on monoamine and metabolite levels in
      various brain areas. The in vitro receptor binding and monoamine uptake
      inhibition profiles, comprising 29 receptors and four monoamine uptake systems,
      revealed that ocaperidone and risperidone bound primarily, and with the highest
      affinity thus far reported, to serotonin 5HT2 receptors (Ki values of 0.14 and
      0.12 nM, respectively). Further, the drugs bound at nanomolar concentrations to
      the following receptors (Ki values, in nM, for ocaperidone and risperidone,
      respectively): alpha 1-adrenergic (0.46 and 0.81), dopamine D2 (0.75 and 3.0),
      histamine H1 (1.6 and 2.1), and alpha 2-adrenergic (5.4 and 7.3). In contrast,
      haloperidol showed nanomolar affinity for D2 receptors (1.55) and haloperidol
      sensitive sigma sites (0.84) only. The in vitro binding affinity of ocaperidone,
      risperidone, and haloperidol for D2 receptors was exactly the same when measured
      in membranes from rat striatum, nucleus accumbens, tuberculum olfactorium, and
      human kidney cells expressing the cloned human D2 receptor (long form). In vivo
      binding in rats, using intravenous administration of [3H]spiperone, revealed very
      potent occupation by ocaperidone and risperidone of 5HT2 receptors in the frontal
      cortex (ED50 of 0.04-0.03 mg/kg); in this respect, they were 6, 30, and 100 times
      more potent than ritanserin, haloperidol, and clozapine, respectively.
      Ocaperidone occupied D2 receptors in the striatum and the nucleus accumbens with
      similar potency as did haloperidol (ED50 of 0.14-0.16 mg/kg). Risperidone
      revealed biphasic inhibition curves in the latter brain areas, indicating that
      [3H] spiperone labeled both 5HT2 receptors (occupied by risperidone at less than
      0.04 mg/kg) and D2 receptors (risperidone ED50 of approximately 1 mg/kg). In the
      tuberculum olfactorium, 5HT2 and D2 receptors were also distinguished with
      risperidone. The ED50 values for occupation of the latter were for ocaperidone
      and risperidone 2 times lower and for haloperidol 2 times higher than in the
      striatum. Ocaperidone, risperidone, and haloperidol readily increased the levels
      of the dopamine metabolites 3,4-dihydroxybenzene acetic acid and homovanillic
      acid in the striatum, the nucleus accumbens, the tuberculum olfactorium, and, to
      some extent, the frontal cortex. Dose-response curve shapes were markedly
      different; with ocaperidone maximal levels were reached at 0.16 mg/kg and
      maintained to 10 mg/kg; with risperidone the levels tended to increase
      continuously up to 10 mg/kg. Haloperidol produced dome-shaped curves (maximum at
      0.16-0.63 mg/kg).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1372086
TI  - Selectivity of amino acid transmitters acting at N-methyl-D-aspartate and amino-3
      hydroxy-5-methyl-4-isoxazolepropionate receptors.
AB  - The endogenous neurotransmitter candidates L-aspartate, L-cysteine sulfinate
      (CSA), L-glutamate, L-homocysteate (HCA), and the endogenously occurring analogue
      quinolinate were compared in terms of potency, maximal activity, and selectivity
      for steady state activation of N-methyl-D-aspartate (NMDA) and non-NMDA [(RS)
      amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)] types of glutamate
      receptors expressed in Xenopus oocytes injected with mRNA isolated from rat brain
      (minus cerebellum). Selective activation of NMDA receptors was achieved by
      deleting Mg2+ and including 3-10 microM glycine in the perfusion medium and by
      applying ligands in the presence of 30 microM quisqualate, which blocks the AMPA
      receptor and desensitizes the oocyte's own Ca(2+)-dependent Cl- current. Oocytes
      were voltage clamped, and steady state inward currents were measured in response
      to perfusion with agonists at known concentrations. Under the NMDA receptor
      preferring condition, the potency rank order was L-glutamate (EC50 = 2.2 microM,
      95% confidence interval = 1.4-3.6 microM) greater than L-aspartate (13 microM) =
      HCA (13 microM) greater than CSA (59 microM) greater than quinolinate (greater
      than or equal to 7200 microM). All amino acids tested evoked similar maximal
      currents, which were 120-159% that of NMDA itself. The Hill coefficient was
      greater than 1 for all agonists except L-HCA (0.6), which might reflect
      heterogeneity of NMDA receptors expressed. This was supported by the finding that
      glycine was more potent in combination with HCA than NMDA, in activating NMDA
      receptors. To study the activity of agonists at AMPA receptors, glycine and
      quisqualate were omitted and 1 mM Mg2+ was included to block NMDA receptors.
      Ca(2+)-dependent Cl- currents activated by L-glutamate were prevented by
      inclusion of 0.4 M ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'
      tetraacetic acid in the recording electrode. All amino acids were less potent at
      AMPA receptors than at NMDA receptors; the potency rank order for steady state
      activation of AMPA receptors was L-glutamate (EC50 = 11 microM, 95% confidence
      interval = 7.3-18 microM) greater than HCA (430 microM) greater than CSA (3300
      microM). L-Aspartate and quinolinate produced little or no inward current even up
      to 10 mM, i.e., were inactive at forebrain AMPA receptors. The maximal currents
      activated by all amino acids at steady state were 5-10% that of kainate,
      presumably due to severe desensitization of the AMPA receptor by the natural
      agonists. These results are consistent with L-glutamate acting as a mixed agonist
      at both AMPA and NMDA synaptic receptors and L-aspartate being involved
      exclusively in NMDA receptor-mediated synapses.

PMID- 1372085
TI  - Activation of beta-adrenergic receptors inhibits Ca2+ entry-mediated generation
      of inositol phosphates in the guinea pig myometrium, a cyclic AMP-independent
      event.
AB  - In the guinea pig myometrium, carbachol, oxytocin, and fluoroaluminates
      stimulated the breakdown of phosphatidylinositol 4,5-bisphosphate, which was
      insensitive to pertussis toxin [Biochem. J. 255:705-713 (1988)]. We now
      demonstrate that an increased accumulation of inositol phosphates, with an early
      production of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], could also be obtained
      with K+ (30 mM) and the Ca2+ ionophore ionomycin. Removal of extracellular Ca2+
      or addition of the Ca2+ channel antagonists nifedipine and verapamil almost
      totally abolished stimulations elicited by high K+ and partially attenuated
      receptor- and fluoroaluminate-mediated increases in inositol phosphates.
      Isoproterenol similarly attenuated the accumulation of inositol phosphates
      elicited by carbachol, oxytocin, and fluoroaluminates (maximal inhibition, 35%;
      EC50, 0.5 nM), with no change in the rate of Ins(1,4,5)P3, inositol bisphosphate,
      and inositol monophosphate generation. The beta-adrenergic receptor-induced
      inhibition was prevented by pertussis toxin and could not be reproduced by
      forskolin, indicating that cAMP was not involved. Experimental findings were,
      rather, consistent with a predominant role for Ca2+. Thus, inhibition due to
      isoproterenol was lost in a Ca(2+)-depleted medium and was not additive with that
      caused by nifedipine. Accumulation of inositol phosphates triggered by high K+
      was insensitive to the beta-adrenergic receptor inhibition. The inhibitory effect
      of isoproterenol, similar to that of nifedipine, was counteracted by ionomycin
      and also by the Ca2+ channel agonist Bay K 8644. These data indicate that in the
      myometrium 1) phospholipase C can be activated through a voltage-gated Ca2+ entry
      dependent process that contributes at least partially to the stimulations
      triggered by receptor- and/or guanine nucleotide-binding protein-mediated
      activation and 2) beta-adrenergic receptor activation is linked via a cAMP
      independent, pertussis toxin-sensitive pathway to an inhibition of voltage-gated
      Ca2+ channels, resulting in an attenuation of the Ca(2+)-associated generation of
      inositol phosphates.

PMID- 1372087
TI  - Intracellular guanosine-5'-O-(2-thiodiphosphate) alters the dynamics of receptor
      mediated responses in bullfrog sympathetic neurons.
AB  - The mechanism by which intracellularly applied guanosine-5'-O-(2-thiodiphosphate)
      alters responses to chicken II luteinizing hormone-releasing hormone, muscarine,
      and substance P in bullfrog sympathetic neurons was examined. Whole-cell
      recordings were made from enzymatically dissociated single neurons. Guanosine-5'
      O-(2-thiodiphosphate) was applied intracellularly by adding it to the pipette
      solution with fixed amounts of GTP. Guanosine-5'-O-(2-thiodiphosphate) did not
      affect the proportion of cells that responded to any of the agonists. Guanosine
      5'-O-(2-thiodiphosphate) decreased the amplitude of the responses to submaximal
      concentrations of agonist. At maximal concentrations of agonist, guanosine-5'-O
      (2-thiodiphosphate) did not decrease the response to the first application of
      agonist; however, with guanosine-5'-O-(2-thiodiphosphate) intracellularly,
      successive responses to maximal concentrations of agonist were decreased in
      amplitude and increased in time course. Intracellular guanosine-5'-O-(2
      thiodiphosphate) did not accelerate the rate or magnitude of desensitization to
      substance P. A kinetic model of receptor-guanine nucleotide-binding protein (G
      protein) coupling predicts that a decrease in the available G protein pool should
      decrease both the magnitude and the time course of the build-up of active G
      proteins. The results are consistent with the hypothesis that guanosine-5'-O-(2
      thiodiphosphate) binds tightly to G proteins, thereby effectively decreasing the
      available G protein pool with repeated agonist applications.

PMID- 1372088
TI  - Pharmacologic and radioligand binding studies of 1,4-dihydropyridines in rat
      cardiac and vascular preparations: stereoselectivity and voltage dependence of
      antagonist and activator interactions.
AB  - The pharmacologic and radioligand-binding properties of 1,4-dihydropyridines in
      an activator (Bay K 8644) and an antagonist (nifedipine) series were studied in
      rat tail artery, heart membrane, and neonatal rat ventricular myocytes. The S
      enantiomers of the activator series contracted rat tail artery in the presence of
      15 mM K+ (EC50 values of 10(-8) to 10(-5) M). (S)-Bay K 8644 (I) and its o
      difluoromethoxy analog (III) were the most potent members of the activator series
      examined. The abilities of the activators to stimulate maximum tension response
      of the artery differed with structure; thus, the efficacy of (S)-Bay K 8644 was
      70% that of the analog lacking the 3-carbomethoxy group. The R-enantiomers of the
      activator series and a series of achiral nifedipine analogs were inhibitory in
      the same tissue. The intact-cell binding assay revealed the binding affinities of
      1,4-dihydropyridine antagonists in depolarized cells (50 mM K+) to be higher than
      those in polarized cells (5 mM K+). The ratio KD (polarized)/KD (depolarized) was
      77 for nifedipine (IC50 = 5.4 x 10(-9) M) but was only 2.9 for the weak 3-methoxy
      nifedipine analog (IC50 = 4.8 x 10(-6) M); an approximately linear relationship
      exists between this ratio and the antagonist potency. In marked contrast, and in
      confirmation of previous work [Mol. Pharmacol. 35:541-552 (1989)], the binding
      affinities of activators were not significantly affected by membrane potential,
      regardless of potency. We conclude that the S-enantiomers of Bay K 8644 analogs
      are activators with different potency and efficacy and that the R-enantiomers are
      antagonists, that the binding of 1,4-dihydropyridine antagonists is voltage
      dependent, whereas binding of the activators is not, and that the voltage
      dependence of binding of the antagonists is correlated with the potency of the
      antagonist.

PMID- 1372089
TI  - Structure and site of expression of a murine type II hair keratin.
AB  - We present here a 1770 bp-long cDNA which encodes a murine type II keratin.
      Sequence comparisons of the keratin with those of various type II keratins
      expressed in mouse epidermis and internal stratified epithelia reveal that the
      new keratin is unrelated to epithelial keratins. Rather the structural
      organization of its amino- and carboxyterminal domains and the high content of
      cysteine and proline residues in these regions suggest that the keratin
      represents a murine type II hair keratin. This assumption was confirmed by in
      situ hybridization which localized the mRNA of the keratin in upper cells of the
      hair cortex and in suprabasal cells of the central core unit of filiform papillae
      of the tongue. Hybrid selection analyses revealed that the keratin has a
      molecular weight of 58 kD. It remains to be seen whether the keratin corresponds
      to MHb 3 or MHb 4.

PMID- 1372090
TI  - The low-abundance U11 and U12 small nuclear ribonucleoproteins (snRNPs) interact
      to form a two-snRNP complex.
AB  - A novel small nuclear ribonucleoprotein (snRNP) complex containing both U11 and
      U12 RNAs has been identified in HeLa cell extracts. This U11/U12 snRNP complex
      can be visualized on glycerol gradients, on native polyacrylamide gels, and by
      selection with antisense 2'-O-methyl oligoribonucleotides. RNase H-mediated
      degradation of the U12 snRNA confirmed a direct interaction between the U11 and
      U12 snRNPs. This snRNP complex is the first to be identified involving low
      abundance snRNPs. Selection of the U11/U12 snRNP complex is sensitive to high
      salt, suggestive of a protein-mediated interaction. Secondary structure analyses
      revealed several regions of the U11 snRNP accessible for interaction with other
      RNAs or proteins but no detectable difference between the accessibility of these
      regions in the U11 monoparticle compared with the U11/U12 snRNP complex. There
      are also several accessible single-stranded regions in the U12 snRNP, and
      oligonucleotide-directed RNase H digestion identified nucleotides 28 to 36 of U12
      as containing sequences required for the U11/U12 interaction. Both the U12 snRNP
      and the U11/U12 snRNP complex can be disrupted without altering the
      cleavage/polyadenylation activity of a nuclear extract.

PMID- 1372093
TI  - Simultaneous screening for 11 mutations in the cystic fibrosis transmembrane
      conductance regulator gene by multiplex amplification and reverse dot-blot.
AB  - An assay is described in which 11 mutations in the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene can be screened simultaneously. Six different
      exons of the CFTR gene are amplified in a single multiplex amplification.
      Biotinylated dUTP is incorporated into the different fragments during the
      amplification process. A sample of this mixture is then hybridized to 21
      different poly-dT tailed oligonucleotide probes which are bound to a nylon
      membrane. In order to screen the different mutations in a single step
      hybridization, the length of the different oligonucleotides and the amount used
      in the assay were optimized. The detection is performed by binding avidin
      alkaline phosphatase to the biotin, followed by a chemiluminescent reaction. By
      means of this fast and sensitive assay, about 85% of all the cystic fibrosis
      mutations in the Belgian population can be detected.

PMID- 1372091
TI  - Interaction of phosphatidylinositol 3-kinase-associated p85 with epidermal growth
      factor and platelet-derived growth factor receptors.
AB  - One of the immediate cellular responses to stimulation by various growth factors
      is the activation of a phosphatidylinositol (PI) 3-kinase. We recently cloned the
      85-kDa subunit of PI 3-kinase (p85) from a lambda gt11 expression library, using
      the tyrosine-phosphorylated carboxy terminus of the epidermal growth factor (EGF)
      receptor as a probe (E. Y. Skolnik, B. Margolis, M. Mohammadi, E. Lowenstein, R.
      Fischer, A. Drepps, A. Ullrich, and J. Schlessinger, Cell 65:83-90, 1991). In
      this study, we have examined the association of p85 with EGF and platelet-derived
      growth factor (PDGF) receptors and the tyrosine phosphorylation of p85 in 3T3
      (HER14) cells in response to EGF and PDGF treatment. Treatment of cells with EGF
      or PDGF markedly increased the amount of p85 associated with EGF and PDGF
      receptors. Binding assays with glutathione S-transferase (GST) fusion proteins
      demonstrated that either Src homology region 2 (SH2) domain of p85 is sufficient
      for binding to EGF and PDGF receptors and that receptor tyrosine
      autophosphorylation is required for binding. Binding of a GST fusion protein
      expressing the N-terminal SH2 domain of p85 (GST-N-SH2) to EGF and PDGF receptors
      was half-maximally inhibited by 2 and 24 mM phosphotyrosine (P-Tyr),
      respectively, suggesting that the N-SH2 domain interacts more stably with PDGF
      receptors than with EGF receptors. The amount of receptor-p85 complex detected in
      HER14 cells treated with EGF or PDGF. Growth factor treatment also increased the
      amount of p85 found in anti-PDGF-treated HER14 cells, suggesting that the vast
      majority of p85 in the anti-P-Tyr fraction is receptor associated but not
      phosphorylated on tyrosine residues. Only upon transient overexpression of p85
      and PDGF receptor did p85 become tyrosine phosphorylated. These are consistent
      with the hypothesis that p85 functions as an adaptor molecule that targets PI 3
      kinase to activated growth factor receptors.

PMID- 1372094
TI  - Simple non-radioactive detection of the CFTR mutation N1303K by artificial
      creation of a restriction site.
AB  - N1303K is one of the most frequent non-delta F508 mutations causing cystic
      fibrosis in Central Europe. Since no restriction site is altered by this mutation
      and no other frequent mutations are known so far in exon 21, the detection
      requires a separate and laborious test. A mismatched primer was used to create an
      artificial Hin dIII site in amplified wildtype DNA, which is destroyed by the
      mutation. This allows for rapid and convenient detection by restriction enzyme
      digestion.

PMID- 1372095
TI  - DNA repair investigations in nine Italian patients affected by
      trichothiodystrophy.
AB  - Trichothiodystrophy (TTD) is a rare autosomal recessive disorder characterized by
      brittle hair, mental and growth retardation, peculiar face, ichthyosis, and in
      20% of the reported cases photosensitivity. Cellular photosensitivity due to the
      same genetic defect present in xeroderma pigmentosum group D (XP-D) has been
      described in several patients. Nine patients with clinical symptoms diagnostic
      for TTD have been identified in Italy to date. We report the results of DNA
      repair investigations performed in cultured fibroblasts from these patients and 8
      TTD parents. Survival, DNA repair synthesis and RNA synthesis following UV
      irradiation were all normal in the 8 TTD heterozygous cell strains. Among the 9
      TTD-affected individuals, normal cellular UV sensitivity was observed in the 2
      patients without signs of clinical photosensitivity. In contrast, the other 7 TTD
      cell strains showed a notable reduction in UV-induced DNA repair synthesis (UDS)
      levels, ranging between 40% and 5-15% of normal values. Complementation analysis
      indicated that in the repair-deficient TTD cell strains the genetic defect is the
      same as that present in XP-D cells. The biochemical heterogeneity of the XP-D
      defect in TTD patients characterized by different degrees of defective UDS
      results in different patterns of response to the killing effect of UV light in
      non-proliferating cells.

PMID- 1372092
TI  - SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate
      binding to growth factor receptors.
AB  - The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and
      Ras GTPase-activating protein to autophosphorylated growth factor receptors is
      directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha
      regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with
      several receptor protein-tyrosine kinases, also contains two SH2 domains. Both
      p85 alpha SH2 domains, when expressed individually as fusion proteins in
      bacteria, bound stably to the activated beta receptor for platelet-derived growth
      factor (PDGF). Complex formation required PDGF stimulation and was dependent on
      receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized
      activated beta PDGF receptor which had been immobilized on a filter, indicating
      that SH2 domains contact autophosphorylated receptors directly. Several receptor
      tyrosine kinases within the PDGF receptor subfamily, including the colony
      stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate
      with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85
      alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating
      factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to
      high-affinity sites on these receptors, whose creation is dependent on receptor
      autophosphorylation. The SH2 domains of p85 are therefore primarily responsible
      for the binding of PI 3-kinase to activated growth factor receptors.

PMID- 1372096
TI  - A comparison of the response of unstimulated and stimulated T-lymphocytes and
      fibroblasts from normal, xeroderma pigmentosum and trichothiodystrophy donors to
      the lethal action of UV-C.
AB  - Unstimulated T-lymphocytes from normal donors are significantly more sensitive to
      the lethal effects of UV-C than either stimulated T-lymphocytes or fibroblasts as
      judged by colony-forming ability. Data from other studies suggest that excision
      repair is more effective in stimulated than unstimulated T-lymphocytes leading to
      the prediction that these differences in survival should be minimal in cells
      established from excision defective donors. The prediction was met with XP6BR, a
      donor of unknown complementation group. For 3 XP's from complementation group D,
      however, enhanced survival in stimulated T-cells was observed. With cells from an
      excision-defective TTD who was included in complementation group D of XP both
      fibroblasts and unstimulated T-lymphocytes were hypersensitive. For a second
      excision defective TTD patient who was excluded from complementation group D, the
      unstimulated T-lymphocytes were more resistant than those of normal donors
      although the fibroblasts were hypersensitive. These results suggest that the in
      vitro response of stimulated T-lymphocytes or fibroblasts may not reflect the in
      vivo response of cells, as measured by the response of unstimulated T
      lymphocytes.

PMID- 1372097
TI  - UV-C sensitivity of unstimulated and stimulated human lymphocytes from normal and
      xeroderma pigmentosum donors in the comet assay: a potential diagnostic
      technique.
AB  - We have studied incision-break formation in unstimulated and stimulated
      populations of human T-lymphocytes using the comet (single-cell microgel
      electrophoresis) assay. The frequency of strand breaks 1 h after UV-irradiation
      appears to be far greater in unstimulated than in stimulated lymphocytes from
      normal donors and the excess of strand breaks was observed for a far longer time
      after irradiation. This result corroborates the greater sensitivity of UV-C
      irradiation observed in a colony-forming assay but suggests that the defect may
      relate to a defect in strand rejoining rather than a defect in incision. Few
      strand breaks were seen in either unstimulated or stimulated lymphocytes of four
      xeroderma pigmentosum donors, suggesting that the method may offer a rapid
      diagnostic assay for XP.

PMID- 1372098
TI  - The repair of large DNA adducts in mammalian cells.
AB  - This paper describes experiments involving the measurement of DNA damage and
      repair after treatment with 4-nitroquinoline 1-oxide (4NQO) or aflatoxin B1
      (AFB1) epoxide in a number of mammalian cell cultures primarily associated with
      defects in the excision repair of UV-induced DNA damage. The results with
      transformed derivatives of XP cells belonging to different complementation groups
      showed that the extent of repair of 4NQO adducts at the N2 or C8 of guanosine did
      not correlate to the extent of repair reported by others after UV-irradiation. An
      examination of 4NQO repair in rodent UV-sensitive cell lines from different ERCC
      groups indicated that again there was little correlation between the extent of
      4NQO and UV repair. However, regardless of complementation group those mutants
      that were defective in the repair of pyrimidine dimers and 6,4-photoproducts did
      exhibit a reduced ability to repair the 4NQO N2 guanosine adduct, whereas those
      mutants defective in pyrimidine dimer repair alone were able to repair this
      lesion as normal. In all of these cell lines there was a normal capacity to
      repair the 4NQO C8 guanosine adduct. Less extensive experiments involving AFB1
      epoxide showed an XPC-transformed cell line was able to repair 40% of lesions
      after 6 h, whereas only 20% of repair is seen after UV. The rodent mutant V-C4
      which belongs to the same ionising radiation group as irs2, was partially
      defective in repairing AFB1-induced damage. These experiments highlight the fact
      that although there are many commonalities between the repair of UV damages and
      lesions classed as large DNA adducts differences clearly exist, the most striking
      example here being the repair of the C8 guanosine 4NQO adduct which rarely
      correlates with a defect in UV repair.

PMID- 1372099
TI  - Xeroderma pigmentosum endonuclease complexes show reduced activity on and
      affinity for psoralen cross-linked nucleosomal DNA.
AB  - Two DNA endonuclease complexes have been isolated from the chromatin of normal
      human and xeroderma pigmentosum, complementation group A (XPA), lymphoblastoid
      cells which are active on DNA damaged with psoralen plus long wavelength
      ultraviolet radiation (UVA). In both normal and XPA cells, one endonuclease
      complex, pI 4.6, recognizes the psoralen cross-link and the other endonuclease
      complex, pI 7.6, recognizes the psoralen monoadduct. The levels of activity of
      these complexes from both normal and XPA cells are similar on damaged naked DNA.
      Kinetic analysis of assays using graduated concentrations of substrate revealed
      that selective activity of these endonuclease complexes on 8-MOP plus UVA treated
      DNA correlates with a reduction in Km of these complexes, indicating an increased
      affinity for, or rate of association with, damaged naked DNA. When the damaged
      substrates were reconstituted into core nucleosomes (without histone H1), both
      normal endonuclease complexes showed a 2.5-fold enhancement of activity, which
      correlated kinetically with a further increase in affinity, or rate of
      association (decreased Km), for this damaged nucleosomal substrate. This increase
      in activity and in affinity was reduced but not eliminated when histone H1 was
      present. By contrast, neither XPA endonuclease complex showed this enhanced
      activity on, or affinity for, damaged core nucleosomal DNA, and actually showed
      decreased activity, and affinity, when histone H1 was present. Introduction, via
      electroporation, of either of the normal complexes into 8-MOP plus UVA treated
      XPA cells in culture corrected their DNA-repair defect, further confirming the
      role of these complexes in the repair process.

PMID- 1372100
TI  - Elevated hprt mutant frequency in circulating T-lymphocytes of xeroderma
      pigmentosum patients.
AB  - The mutant frequency to 6-thioguanine resistance in circulating T-lymphocytes
      from 10 xeroderma pigmentosum patients (including complementation groups D and G
      and XP variants) has been determined. A highly significantly elevated frequency
      was observed, compared to age-matched, non-smoking control donors (x 2.1-fold
      higher than the mutant frequency in normal control donors, adjusted for age and
      cloning efficiency, p less than 0.001). The mutant frequency of 5 XP
      heterozygotes was in the normal range, when age, smoking habit and log cloning
      efficiency were taken into account. A number of possible factors which may
      account for the elevated mutant frequency seen in the XP donors (including an
      elevated spontaneous mutation rate, UV mutagenesis of the T-cells as they pass
      through the skin, an effect of environmental mutagens such as tobacco smoke, or
      as a consequence of immune deficiency) are discussed.

PMID- 1372101
TI  - Co-recessive inheritance: a model for DNA repair and other surveillance genes in
      higher eukaryotes.
AB  - The co-recessive inheritance hypothesis proposes that certain recessively
      inherited diseases require homozygosity and/or hemizygosity for defective alleles
      at more than one locus simultaneously for the trait to be expressed. Although
      this hypothesis was originally proposed in the context of defective alleles for
      genes coding for DNA-repair functions, it need not be limited to this context,
      and genetic selection pressure may favor this model for genes involved in
      surveillance of any type. The co-recessive inheritance hypothesis also predicts
      extremely high carrier frequencies, likely affecting much of the general
      population, for defective alleles associated with these rare recessive diseases.
      The model predicts much lower rates of consanguinity between the parents of
      affected individuals than autosomal recessive inheritance, allowing it to be
      tested epidemiologically, and recent data suggest that the hypothesis may be
      valid for some cases of ataxia telangiectasia and xeroderma pigmentosum. The
      model provides possible explanations for a number of otherwise puzzling findings
      in several diseases associated with defective DNA repair.

PMID- 1372102
TI  - Three nonsense mutations responsible for group A xeroderma pigmentosum.
AB  - The molecular basis of xeroderma pigmentosum (XP) group A was studied and 3
      nonsense mutations of the XP-A complementing gene (XPAC) were identified. One was
      a nucleotide transition altering the Arg-228 codon (CGA) to a nonsense codon
      (TGA). This transition creates a new cleavage site for the restriction
      endonuclease HphI. Of 21 unrelated Japanese XP-A patients examined, 1 (XP39OS)
      was a homozygote for this mutation and 3 were compound heterozygotes for this
      mutation and for the splicing mutation of intron 3 reported previously which is
      the most common mutation in Japanese patients and creates a new cleavage site for
      the restriction endonuclease AlwNI. The second mutation was a nucleotide
      transition altering the Arg-207 codon (CGA) to a nonsense codon (TGA). A
      Palestinian patient (XP12RO) who had severe symptoms of XP was homozygous for
      this mutation. The third mutation was a nucleotide transversion altering the Tyr
      116 codon (TAT) to a nonsense codon (TAA). This transversion creates a new
      cleavage site for the restriction endonuclease MseI. Of the Japanese patients, 2
      with severe clinical symptoms had this mutant allele. One was a compound
      heterozygote for this mutation and for the splicing mutation, and the other was
      heterozygous for this mutation and homozygous for the splicing mutation. Although
      most XP-A patients such as XP12RO have severe skin symptoms and neurological
      abnormalities of the de Sanctis-Cacchione syndrome, patient XP39OS was an
      atypical XP-A patient who had mild skin symptoms and minimal neurological
      abnormalities. Our results suggest that the clinical heterogeneity in XP-A is due
      to different mutations in the XPAC gene. Moreover, our data indicate that almost
      all Japanese cases of XP-A are caused by one or more of the 3 mutations, i.e.,
      the splicing mutation of intron 3 and the 2 nonsense mutations of codons 116 and
      228. Therefore, by restriction fragment length polymorphism analysis of PCR
      amplified DNA sequences using the 3 restriction enzymes described above, rapid
      and reliable diagnosis of XP-A can be achieved in almost all Japanese subjects
      including prenatal cases and carriers.

PMID- 1372103
TI  - Identification of splicing mutations of the last nucleotides of exons, a nonsense
      mutation, and a missense mutation of the XPAC gene as causes of group A xeroderma
      pigmentosum.
AB  - Four mutations of the XPAC gene were identified as molecular bases of different
      UV-sensitive subgroups of xeroderma pigmentosum (XP) group A. One was a G to C
      transversion at the last nucleotide of exon 4 in GM1630/GM2062, a little less
      hypersensitive subgroup than the most sensitive XP2OS/XP12RO. The second mutation
      was a G to A transition at the last nucleotide of exon 3 in GM2033/GM2090, an
      intermediate subgroup. Both mutations caused almost complete inactivation of the
      canonical 5' splice donor site and aberrant RNA splicing. The third mutation was
      a nucleotide transition altering the Arg-211 codon (CGA) to a nonsense codon
      (TGA) in another allele of GM2062. The fourth mutation was a nucleotide
      transversion altering the His-244 codon (CAT) to an Arg codon (CGT) in XP8LO, an
      intermediate subgroup. Our results strongly suggest that the clinical
      heterogeneity in XP-A is due to different mutations in the XPAC gene.

PMID- 1372104
TI  - UV-induced base substitution mutations in a shuttle vector plasmid propagated in
      group C xeroderma pigmentosum cells.
AB  - To assess the contribution to mutagenesis of human DNA repair defects, the UV
      irradiated shuttle vector plasmid pZ189 was propagated in fibroblasts derived
      from a xeroderma pigmentosum (XP) patient in DNA repair complementation group C.
      In comparison to results with DNA repair-proficient human cells (WI-38 VA13), UV
      irradiated pZ189 propagated in the XP-C (XP4PA(SV)) cells showed fewer surviving
      plasmids and a higher frequency of mutated plasmids. Base sequence analysis of 67
      mutated plasmids recovered from the XP-C cells revealed similar classes of point
      mutations and mutation spectrum, and a higher frequency of G:C to A:T transitions
      along with a lower frequency of transversions among plasmids with single or
      tandem mutations compared to plasmids recovered from the normal line. Most single
      base substitution mutations (83%) occurred at G:C base pairs in which the 5'
      adjacent base of the cytosine was thymine or cytosine. These results indicate
      that the DNA repair defects in XP-C, in comparison to data previously reported
      for XP-A, XP-D and XP-F, result in different UV survival and mutation frequency
      but in similar types of base substitution mutations.

PMID- 1372105
TI  - Correlation between DNA methylation and expression of O6-methylguanine-DNA
      methyltransferase gene in cultured human tumor cells.
AB  - Approximately 20% of human tumor cell strains are deficient in a DNA repair
      protein, O6-methylguanine-DNA methyltransferase (MGMT), and are called Mer-
      strains. In an attempt to determine the molecular basis for the extinction of
      MGMT expression in Mer- human cells, the distribution of DNA methylation sites in
      and around the exon sequences of the repair gene was compared in 6 Mer+ (repair
      proficient) and 12 Mer- cell lines. Southern blot analysis of the genomic DNA
      digested with isoschizomeric restriction endonucleases MspI and HpaII to detect 5
      methylcytosine in CCGG sequences indicated that the DNA of all the Mer+ cells but
      of none of the Mer- cells is heavily methylated in the exon-containing regions.
      The methylation pattern contradicts the general belief that inactive genes are
      hypermethylated compared to hypomethylation of transcriptionally active genes. It
      appears that the regulation of the MGMT gene in human cells is much more complex
      than simply dictated by its methylation level.

PMID- 1372106
TI  - Mitochondrial DNA repair by photolyase.
AB  - Photolyase genes of Saccharomyces cerevisiae and Escherichia coli were expressed
      in S. cerevisiae and photoreactivation in nuclei and mitochondria of the host
      cells was analyzed by determination of survival and petit rates. Yeast photolyase
      was able to repair mitochondrial DNA effectively, whereas E. coli photolyase
      could reduce only a small fraction of the petit rate produced by UV irradiation.
      Analysis using fusion between yeast photolyase and E. coli lacZ genes as well as
      a chimeric gene between yeast and E. coli photolyase genes suggests the
      importance of the protruding amino terminal region of the yeast photolyase for
      its transport into mitochondria. A significant similarity between the protruding
      amino termini of yeast photolyase and yeast uracil-DNA-glycosylase suggests a
      common functional importance of the terminal sequences for both DNA repair
      enzymes.

PMID- 1372107
TI  - Joint workshop on DNA repair mechanisms and embryo manipulation. Report of the
      Third Annual Workshop of the Institute for Molecular and Cellular Biology, Osaka
      University, held in Osaka (Japan), 21-23 January 1991.

PMID- 1372108
TI  - The XPD complementation group. Insights into xeroderma pigmentosum, Cockayne's
      syndrome and trichothiodystrophy.
AB  - The xeroderma pigmentosum complementation group D is defined by more than 30
      unrelated individuals of whom less than half show major abnormalities of the
      central nervous system, once considered to be the hallmark of the group.
      Fibroblasts from the great majority of these individuals show very considerable
      sensitivity to UV light in vitro despite the fact that the cells carry out what
      appears to be substantial excision repair, as judged from repair synthesis and
      incision activity. This article reviews the XPD group and the defects in cellular
      DNA repair and examines the lack of correlation between repair and the appearance
      of neurological abnormalities. The article also discusses the recent awareness
      that at least some members of two other inherited conditions, trichothiodystrophy
      and Cockayne's Syndrome, carry mutations in the XPD gene.

PMID- 1372109
TI  - X-linked recessive nephrolithiasis with renal failure.

PMID- 1372110
TI  - Molecular transduction. Do the ear's links link?

PMID- 1372111
TI  - CFTR mechanism.

PMID- 1372112
TI  - Solitary eosinophilic granuloma in the frontal lobe: case report.
AB  - A rare case of a solitary eosinophilic granuloma in the brain is reported. The
      mass, located in the right frontal lobe, mimicked a glioma not only grossly, but
      also by neuroimaging. The lesion was confirmed to be an eosinophilic granuloma by
      electron microscopy and immunohistochemical staining for S-100 protein and HLA
      DR.

PMID- 1372113
TI  - Transient expression of neuropeptide Y and its C-flanking peptide
      immunoreactivities in the spinal cord and ganglia of human embryos and fetuses.
AB  - An immunohistochemical study of spinal cord, dorsal root and sympathetic ganglia
      of human embryos and fetuses demonstrated that neuropeptide Y and its C-flanking
      peptide could be detected in seven-week-old embryos but were absent or difficult
      to demonstrate after the 17th week of gestation. The peptides were found in
      several structures of the spinal cord, e.g. fibres in the dorsal portion of the
      lateral funiculus, cell bodies and fibres in the dorsal horn, and motoneurons,
      and also in numerous primary sensory neurons of dorsal root ganglia. They were
      also present in sympathetic neurons and since these are the only structures
      expressing neuropeptide Y and its C-flanking peptide in the adult, it must be
      concluded that their presence in other neurons is a transient developmental
      feature. To assist in understanding the relationship of these transient
      structures with other spinal and sensory neurons, a comparison was made with
      other neuronal structures showing immunoreactivity for two general neuronal
      markers, neurofilaments and protein gene product 9.5, and two neuropeptides
      present in primary sensory afferents, somatostatin and substance P. In the dorsal
      root ganglia, numerous neuropeptide Y- and C-flanking peptide-immunoreactive
      neurons were observed before substance P- or somatostatin-immunoreactive cells
      could be detected. Therefore, neuropeptide Y and its C-flanking peptide could
      represent a primitive peptidergic system appearing before primary sensory neurons
      express their characteristic adult phenotype. The fibres of the lateral funiculus
      showing immunoreactivity for neuropeptide Y and its C-flanking peptide were
      longitudinally orientated and could be detected at all cephalocaudal levels of
      the spinal cord. Comparison with the other immunohistochemical markers indicated
      that they were not primary sensory afferents. At least some of them probably
      originated from neuropeptide Y- and C-flanking peptide-immunoreactive neurons of
      the dorsal horn, that may be considered to be a subset of early-appearing
      interneurons.

PMID- 1372114
TI  - Unilateral naris closure and vascular development in the rat olfactory bulb.
AB  - The blood supply to the brain has been linked closely to nervous system function
      and metabolism, thereby possibly playing a direct role in brain maturation.
      Previously, we demonstrated that closure of an external naris early in life
      results in large changes within the olfactory bulb, including reductions in
      laminar volume and cell number and a rapid decline in metabolism and protein
      synthesis. To understand the role of the blood supply in the dramatic changes
      following naris closure, the present study examines the development of olfactory
      bulb vasculature in unilaterally odor-deprived and control rats. On post-partum
      day 1 (P1; the day after birth), littermate rat pups underwent either unilateral
      naris occlusion or sham surgery. On P5, P10, P15, P20, P30 and P60, animals were
      perfused with an india ink-gelatin mixture to assess blood vessel amount and
      complexity. Densitometric analyses were performed to obtain values of blood
      vessel area ratios (vessel area/tissue area), branch point number and branch
      point density. Considerable vessel development in all bulbs occurred over the
      first two to three weeks post-partum. By P20, large reductions in vessel area
      ratios were observed in all constituent laminae of deprived bulbs. While similar
      reductions in number of vessel branch points/tissue area were seen, few changes
      were noted in the number of branch points/vessel area. The effects were primarily
      confined to early developmental periods: bulb vasculature in animals deprived at
      older ages (P40) appeared normal. The results indicate that the vasculature
      responds to alterations in sensory stimulation early in life, therefore
      potentially playing an important regulative role in neural development.

PMID- 1372115
TI  - Fast excitatory postsynaptic potentials and the responses to excitant amino acids
      of sympathetic preganglionic neurons in the slice of the cat spinal cord.
AB  - The properties of the excitatory postsynaptic potential evoked by focal
      stimulation and of the responses to excitatory amino acids were examined by
      intracellular recording from sympathetic preganglionic neurons in upper thoracic
      spinal cord slices of the adult cat. Single stimuli to the region dorsal to the
      intermedio-lateral nucleus evoked short-latency, presumably monosynaptic,
      excitatory postsynaptic potentials. The reversal potential of this response was 
      2.2 mV and became more negative when external Na+ or K+ concentration was
      decreased. The excitatory postsynaptic potential was depressed by the non
      selective excitatory amino acid receptor antagonist cis-2,3-piperidine
      dicarboxylic acid and enhanced by a glutamate uptake inhibitor. The non-N-methyl
      D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2.3-dione abolished
      the excitatory postsynaptic potential in 72% of neurons. In the remaining
      neurons, this antagonist only depressed the potential and unmasked a slower
      component which was abolished by the N-methyl-D-aspartate receptor antagonist D,L
      2-amino-5-phosphonovaleric acid. In the presence of tetrodotoxin all neurons
      tested were depolarized by glutamate or aspartate, as well as by the selective
      agonists quisqualate, alpha-amino-3-hydroxy-5-methylisoxazole propionic acid,
      kainate and N-methyl-D-aspartate. The glutamate-evoked depolarization reversed at
      a membrane potential of -2.0 mV and at a more negative value when external Na+ or
      K+ concentration was decreased. The response to alpha-amino-3-hydroxy-5
      methylisoxazole propionic acid was abolished by 6-cyano-7-nitroquinoxaline-2,3
      dione in all neurons tested and that to kainate in only one-third of the cells.
      In the remainder the response to kainate was only slightly depressed by this
      antagonist. The responses to glutamate and aspartate were only slightly depressed
      by the combined action of the various amino acid receptor antagonists used. The
      responses to N-methyl-D-aspartate were abolished by D,L-2-amino-5
      phosphonovaleric acid. The punched-out region of the intermedio-lateral nucleus,
      maintained in vitro, released glutamate and aspartate in the absence of
      stimulation. Field stimulation (20 Hz) enhanced release by between 40 and 100%.
      The increase was prevented by superfusion with calcium-free Krebs. It is
      concluded that excitatory amino acids, acting on both N-methyl-D-aspartate and
      non-N-methyl-D-aspartate receptors, but mainly on the latter, are likely
      mediators of the monosynaptic excitatory postsynaptic potential evoked in
      sympathetic preganglionic neurons by the stimulated region. The efflux data
      suggest that glutamate and aspartate are among the mediators.

PMID- 1372116
TI  - Separate neuronal populations of the rat globus pallidus projecting to the
      subthalamic nucleus, auditory cortex and pedunculopontine tegmental area.
AB  - The topographic arrangement of globus pallidus neurons sending axons to the
      subthalamic nucleus, auditory cortex and pedunculopontine tegmental nucleus was
      studied in the rat using retrograde fluorescent tracers. Neurons projecting to
      the subthalamic nucleus were localized in the rostral part of the globus
      pallidus, while neurons projecting to the auditory cortex and to the
      pedunculopontine tegmental nucleus were located in the caudal part. The two
      populations of pallidocortical and pallidotegmental neurons were also distributed
      in a separate manner within the caudal globus pallidus. The former neurons were
      large and located more ventromedially, whereas the latter were medium-sized and
      located more dorsolaterally. Using a retrograde fluorescent tracing technique
      combined with choline acetyltransferase immunofluorescence histochemistry, it was
      found that a vast majority of pallidocortical neurons expressed choline
      acetyltransferase immunoreactivity, and that pallidotegmental neurons rarely
      exhibited choline acetyltransferase immunoreactivity. A method of retrograde
      tracing with wheatgerm agglutinin conjugated with horseradish peroxidase
      associated to immunohistochemistry for glutamate decarboxylase confirmed the
      GABAergic nature of the pallidotegmental pathway. The present study revealed the
      independent nature of the globus pallidus neurons projecting to the subthalamic
      nucleus, auditory cortex and pedunculopontine tegmental nucleus. Within this
      cellular arrangement, the presence of functionally distinct neuronal populations
      at the caudal pallidal level was also identified, with large cholinergic cells
      innervating the neocortex and medium-sized GABAergic cells "feeding" the
      mesencephalic tegmentum.

PMID- 1372117
TI  - Separate neuronal populations of the rat substantia nigra pars lateralis with
      distinct projection sites and transmitter phenotypes.
AB  - The topographic organization of the nigral cells sending axons to the striatum,
      amygdala and inferior colliculus was studied in the rat substantia nigra pars
      lateralis by using retrograde fluorescent tracers. Nigral perikarya projecting to
      the inferior colliculus were located dorsolaterally within the substantia nigra
      pars lateralis, whereas nigral perikarya projecting to the striatum or to the
      amygdala were mostly situated ventromedially within the substantia nigra pars
      lateralis. The transmitter substances of the nigrotectal cells were examined by
      combining a retrograde tracing method with immunohistochemistry for tyrosine
      hydroxylase or glutamate decarboxylase. Nigral neurons projecting to the inferior
      colliculus lacked tyrosine hydroxylase immunoreactivity, but exhibited
      immunoreactivity for glutamate decarboxylase. The substantia nigra pars lateralis
      is made up of different neuronal populations: one projecting to the inferior
      colliculus and another directed to the striatum and amygdala. The pars lateralis
      pathway to the inferior colliculus utilized GABA as a neurotransmitter, whereas
      the previously characterized nigral cells projecting to the striatum and superior
      colliculus use GABA and dopamine as neurotransmitters.

PMID- 1372118
TI  - Choline acetyltransferase-immunoreactive neurons in the rat entopeduncular
      nucleus.
AB  - Using a monoclonal antibody against choline acetyltransferase, neurons of the rat
      entopenduncular nucleus were found to express choline acetyltransferase
      immunoreactivity. These cholinergic cells were located mostly in the rostral
      portion of the entopeduncular nucleus with a marked decrease towards its caudal
      portion. To identify their target sites, a retrograde fiber tracing technique was
      combined with immunohistochemistry for choline acetyltransferase. After injection
      of wheatgerm agglutinin conjugated with horseradish peroxidase into the habenula,
      some of the entopedunculo-habenular cells were found to be immunoreactive for
      choline acetyltransferase. The cells in the peripallidal region (the substantia
      innominata, nucleus basalis magnocellularis and ansa lenticularis) with choline
      acetyltransferase immunoreactivity did not contain horseradish peroxidase.
      Following injection of fluorescent tracer into the frontal cerebral cortex,
      retrogradely labeled cells were observed in the rostral part of the
      entopedunucular nucleus. A majority of these entopedunculo-cortical cells
      exhibited choline acetyltransferase immunoreactivity, similar to the cells of the
      peripallidal region projecting to the neocortex. Employing two different
      fluorescent tracers, entopedunculo-cortical cells were shown to constitute a
      distinct cell population from the numerous entopedunculo-habenular cells. The
      present study demonstrated, in the rat entopeduncular nucleus, the presence of
      cholinergic neurons that projected to the neocortex and habenula.

PMID- 1372119
TI  - Choice of treatment for thyrotoxicosis.

PMID- 1372120
TI  - Clinical management of the patient with an acute myocardial infarction.
AB  - The clinical care of patients with myocardial infarction has evolved to embrace
      not only palliative measures but also strategies to decrease pre-hospital delay
      and direct interventional measures to promote myocardial salvage. Thrombolysis
      has emerged as a therapy that significantly improves mortality and morbidity,
      particularly if administered early in the infarction process. Major thrombolytic
      agents and their administration schedules, adverse reactions, and adjunctive
      therapies are reviewed.

PMID- 1372121
TI  - Development of specific enzyme-linked immunosorbent antibody assay systems for
      the detection of chicken immunoglobulins G, M, and A using monoclonal antibodies.
AB  - The aim of the present study was the development of a sensitive and specific
      ELISA system for the quantitative and qualitative assay of chicken Ig Isotypes G,
      M, and A using monoclonal antibodies. Five hybridoma cell lines were developed
      that synthesized specific antibodies against chicken IgG and three lines each
      producing specific antibodies against IgM or IgA. Using an immunodiffusion test,
      the subclasses were determined. Isolation of monoclonal antibodies from ascites
      was carried out by way of affinity chromatography with protein G sepharose. The
      purity of the eluates were determined by both SDS-PAGE and HPLC. A Sandwich ELISA
      was found to be the most suitable technique for the assay. Specificity testing
      was carried out by Western blotting. An epitope analysis was also carried out. By
      variation of the single steps concerning incubation times, quantities, and
      concentrations of the substances to be applied, the whole procedure was
      optimized. Assay limits for individual Ig isotypes were determined. The limits
      were 20 ng/mL for IgG, 80 ng/mL for IgM, and 160 ng/mL for IgA.

PMID- 1372123
TI  - [Diagnosis of cancer of the prostate].

PMID- 1372122
TI  - The presence and inactivation of trypsin inhibitors, tannins, lectins and amylase
      inhibitors in legume seeds during germination. A review.
AB  - During the germination of legume seeds, enzymes become active in order to degrade
      starch, storage-protein and proteinaceous antinutritional factors. The
      degradation of storage-protein is necessary to make peptides and amino acids
      available in order to stimulate seed growth and early plant growth. Proteinaceous
      antinutritional factors such as amylase inhibitors, lectins and trypsin
      inhibitors are present in legume seeds and protect them against predators.
      However, during germination, they degrade to a lower level by the action of
      several enzymes. The effect of germination on the content and activity of amylase
      inhibitors, lectins, tannins and trypsin inhibitors is discussed.

PMID- 1372124
TI  - [Use of a synthetic prostacyclin in extracorporeal circulation].
AB  - Using a prostacyclin in conjunction with standard heparin might limit the
      occurrence of post-extracorporeal circulation (ECC) thrombopathy and reduce the
      risk of haemorrhage inherent in this technique. For this reason, we studied the
      effect of the prostacyclin analogue Iloprost (ZK 36 374), a drug which is active
      in man when given orally with a biological half-life of 30 min, and devised a
      double-blind randomized trial to evaluate the potential benefit of Iloprost
      versus placebo in 2 groups of 15 patients (A: placebo, B: Iloprost). An infusion
      of the drug in incremental doses (up to 12 ng kg-1 min-1) was begun before
      starting the ECC and was stopped at the end of the cardiopulmonary bypass, at the
      time of protamine injection. Significant arterial hypotension was observed during
      ECC in two patients of the Iloprost group. Comparison between Iloprost and
      placebo groups showed that the mean number of platelets was not significantly
      higher in the Iloprost group 20 min after the ECC and during the early post
      operative recovery period. Platelet aggregability was higher after surgery in the
      Iloprost group than in the placebo group. There was no significant difference in
      post-bypass bleeding between the two groups. Thus, Iloprost does not reduce the
      fall in circulating platelets observed during cardiopulmonary bypass, but it
      might help in preserving the platelet function. However, the potential usefulness
      of the drug is limited by adverse haemodynamic reactions.

PMID- 1372126
TI  - A prospective randomised trial of 4 Gy or 8 Gy single doses in the treatment of
      metastatic bone pain.
AB  - 270 patients with painful bone metastases requiring palliative radiotherapy were
      randomised to receive single fractions of 4 Gy or 8 Gy in a randomised trial.
      Pain scores and analgesic usage were recorded before treatment and at 2, 4, 8 and
      12 weeks. Pain was assessed by patients on a 4 point graded scale using pain
      charts administered by a central trials office. Response was defined as an
      improved rating compared to the pretreatment value. Compliance with the pain
      chart was 72% at 4 weeks. At 4 weeks, the actual response rates were 69% for 8 Gy
      and 44% for 4 Gy (p less than 0.001), but there was no difference in complete
      response (no pain) rates at 4 weeks or duration of response between the two arms.
      It is concluded that 8 Gy gives a higher probability of pain relief than 4 Gy,
      but that 4 Gy can be an effective alternative in situations of reduced tolerance.

PMID- 1372125
TI  - Modulation of ion channels by somatostatin and acetylcholine.
AB  - Somatostatin and muscarinic acetylcholine receptors are similar as far as
      modulation of voltage-gated Ca2+ channels and anomalously rectifying K+ channels
      are concerned. Activation of either type of receptors induces inhibition of Ca2+
      channels and activation of anomalous K+ channels without depending on
      intracellular cAMP. Somatostatin appears to act on the same receptor subtype for
      these two actions since somatostatin receptors are homogenous in pituitary cells
      (Srikant and Patel, 1982; Tran et al., 1985) where the peptide produces these two
      effects as well as an inhibition of adenylate cyclase. In the case of muscarinic
      receptors, however, it remains unclear whether the same subtype of receptors is
      involved in both inhibition of Ca2+ channels and activation of K+ channels.
      Activation of muscarinic receptors in hippocampal neurones evidently produces a
      cAMP-independent suppression of Ca2+ channel. In cardiac cells, however,
      muscarinic stimulation does not cause a cAMP-independent suppression of Ca2+
      channels but does activate an anomalous rectifier. These findings do not
      necessarily mean that the muscarinic receptor involved in the inhibition of Ca2+
      channels in hippocampal neurones is not of m2 type which is assumed to mediate
      the activation of anomalous K+ channels in cardiac cells. There is no evidence
      that cardiac Ca2+ channels are identical to hippocampal Ca2+ channels susceptible
      to muscarinic inhibition. In addition, a similar argument could be applied to G
      proteins coupling muscarinic receptors to Ca2+ channels in neurones and cardiac
      myocytes. In this regard, it should be noted that activation of GABAB receptors
      or mu and delta opiate receptors, an event known to inhibit adenylate cyclase
      activity through a PTX-sensitive Gi protein, also produces both inhibition of
      Ca2+ channels and activation of anomalous K channels in a cAMP-independent
      manner. This close correlation between inhibition of adenylate cyclase activity
      and cAMP-independent modulation of Ca2+ and K+ channels suggests the possible
      involvement of m2 subtype in the inhibition of Ca2+ channels in hippocampal
      neurones. Circumstantial evidence indicates that anomalous K+ channels are
      directly activated by alpha subunits of Gi, but not Go, proteins. The alpha
      subunit of Go protein seems to mediate inhibition of the Ca2+ channel, probably
      in a direct manner. The most striking difference between somatostatin and
      muscarinic receptors would be their opposite actions on the M channel. All the
      inhibitory receptors on the M channel, including m1 and m3 receptors, are known
      to stimulate PI hydrolysis via a PTX-insensitive G protein.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1372127
TI  - [Preventive measures in thromboembolic accidents in surgery].

PMID- 1372128
TI  - Less is more: a med/surg flow sheet.

PMID- 1372129
TI  - The specificity of translational control switched with transfer RNA identity
      rules.
AB  - The interaction of Escherichia coli threonyl-transfer RNA (tRNA) synthetase with
      the leader sequence of its own messenger RNA inhibits ribosome binding, resulting
      in negative translational feedback regulation. The leader sequence resembles the
      substrate (tRNA(Thr)) of the enzyme, and the nucleotides that mediate the correct
      recognition of the leader and the tRNA may be the same. A mutation suggested by
      tRNA identity rules that switches the resemblance of the leader sequence from
      tRNA(Thr) to tRNA(Met) causes the translation of the threonyl-tRNA synthetase
      messenger RNA to become regulated by methionyl-tRNA synthetase. This identity
      swap in the leader messenger RNA indicates that tRNA identity rules may be
      extended to interactions of synthetases with other RNAs.

PMID- 1372130
TI  - Stem-cell gene therapy moves toward approval.

PMID- 1372132
TI  - Germ plasm revisited and illuminated.

PMID- 1372133
TI  - Efficiency and limitations of the hn-cDNA library approach for the isolation of
      human transcribed genes from hybrid cells.
AB  - The use of splice donor site consensus sequences as primers in cDNA synthesis (to
      make a cDNA library from heterogeneous RNA or unprocessed transcript--an hn-cDNA
      library) and the screening of such an hn-cDNA library with human repeat DNA probe
      in order to isolate human genes from somatic cell hybrids have been demonstrated.
      Here, we optimize and evaluate the efficiency and limitations of the approach.
      Computer analysis of genomic sequences of 22 randomly selected human genes
      indicated that hexamers CTTACC, CTCACC, and CCTACC were most efficient at
      beginning first-strand cDNA synthesis at donor splice sites of hnRNA and
      suggested that the procedure is efficient for priming cDNA synthesis of at least
      one exon from most every gene. Primer extension experiments established
      conditions in which the primers would initiate synthesis of cDNA starting from a
      perfectly matched position on the RNA template at more than 60-fold higher yield
      than any other product. By isolation of a clone containing exon III of the human
      DNA repair gene ERCC1, we indicate that the approach is capable of cloning exons
      from weakly expressed genes. Sequencing of clones revealed a structure of hn-cDNA
      clones consistent with the expectations of the cloning strategy and indicated the
      potential of the clones in detecting polymorphisms. Finally, we demonstrate that
      the expression of these hn-cDNA sequences in cells can be detected efficiently at
      the hnRNA level by reverse transcriptase-polymerase chain reaction (RT/PCR).

PMID- 1372131
TI  - Cytokine stimulation of multilineage hematopoiesis from immature human cells
      engrafted in SCID mice.
AB  - Severe combined immunodeficient (SCID) mice transplanted with human bone marrow
      were treated with human mast cell growth factor, a fusion of interleukin-3 and
      granulocyte-macrophage colony-stimulating factor (PIXY321), or both, starting
      immediately or 1 month later. Immature human cells repopulated the mouse bone
      marrow with differentiated human cells of multiple myeloid and lymphoid lineages;
      inclusion of erythropoietin resulted in human red cells in the peripheral blood.
      The bone marrow of growth factor-treated mice contained both multipotential and
      committed myeloid and erythroid progenitors, whereas mice not given growth
      factors had few human cells and only granulocyte-macrophage progenitors. Thus,
      this system allows the detection of immature human cells, identification of the
      growth factors that regulate them, and the establishment of animal models of
      human hematopoietic diseases.

PMID- 1372134
TI  - Predictive factors for outcome in treatment of metastatic nonseminomatous germ
      cell tumors.
AB  - In recent years less intensive chemotherapy programs for patients with metastatic
      nonseminomatous germ cell tumors with high likelihood of cure have been proposed,
      and the use of innovative more intensive treatments for patients with less
      favorable prognosis is being explored. The development of validated prognostic
      classifications has thus become important. In 77 patients with metastatic
      nonseminomatous germ cell tumors treated with chemotherapy, the ability of
      various prognostic factors to predict outcome of treatment was assessed. The
      multifactorial prognostic classification (Indiana classification) and a
      mathematical predictive formula correctly allocated patients to low- or high-risk
      groups in 84.4 percent and 87.0 percent of cases. The multifactorial
      classification system (M.D. Anderson system) correctly allocated patients in 61
      percent of cases. The presence of serum beta HCG levels over 1,000 mg/mL, a pure
      choriocarcinoma histology and possibly an extragonadal primary origin of tumor
      were found to predict an adverse outcome in a small number of patients. It is
      concluded that use of the Indiana classification or mathematical predictive
      formula is an accurate means of allocating patients with metastatic germ cell
      tumors to high- or low-risk groups and that allocation of patients with pure
      choriocarcinoma histology, very high beta HCG levels, or extragonadal primary
      origin of tumor to the poor prognosis category will improve the accuracy of
      prediction in a few cases.

PMID- 1372135
TI  - A sensitive immunoassay for porcine interferon-alpha.
AB  - Two murine monoclonal antibodies (mAbs) directed against different epitopes on
      recombinant porcine interferon-alpha (IFN-alpha) were selected and used to
      construct a two-site ELISA. This ELISA, when performed in a one-step version,
      detected about 0.5 units ml-1 of IFN-alpha and showed similar sensitivity but
      better precision than a cytopathic effect inhibition bioassay. Estimates of IFN
      alpha in tissue culture medium by the two assays correlated well. In contrast,
      one or several factors in porcine serum reduced the sensitivity of the ELISA.
      Measurements of IFN-alpha in porcine serum was, however, possible in a two-step
      version of the ELISA, with a sensitivity of about 1 unit IFN-alpha ml-1. Results
      of ELISA and bioassay agreed, except that the ELISA possibly produced false
      positive results in two out of a total of 91 sera negative in the bioassay. In
      addition, one of 23 sera positive in the bioassay was negative in the ELISA.

PMID- 1372136
TI  - Isolation of canine C-reactive protein and characterization of its properties.
AB  - C-reactive protein (CRP) was isolated from the acute phase serum of dogs
      subjected to surgical stimulation. Its properties were characterized. Canine CRP
      was isolated by ion-exchange chromatography using DEAE-Sephacel and DEAE-Sephadex
      A-50 and affinity chromatography using protein A-Sepharose CL 4B in combination
      with agar-block electrophoresis. In immunoelectrophoresis, canine CRP had the
      same gamma-mobility as human gamma-type CRP. The molecular weight of purifined
      canine CRP was estimated by gel filtration and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis to be approximately 157,000 and 155,000
      respectively. This CRP was a thermolabile protein which completely lost its
      antigenicity by heating at 70 degrees C for 15 min. The serum concentration of
      CRP in normal beagle dogs ranged from 0.198 to 0.826 micrograms ml-1 (0.486 +/-
      0.170 micrograms ml-1). The concentration was acutely increased by surgery as it
      was in man and was rapidly decreased with convalescence. Dogs can be a useful
      animal model for investigation of the mechanism of CRP production and the
      function of CRP.

PMID- 1372137
TI  - Production of interleukin-2 mRNA by bovine lymph node lymphocytes in response to
      concanavalin A, 12-O-tetradecanoylphorbol-13-acetate, and ionomycin.
AB  - Interleukin-2 (IL-2) is a lymphokine which, upon binding to its receptor, leads
      to the proliferation and differentiation of T-cells (helper, suppressor, and
      cytotoxic) and B-cells. While human and murine IL-2 have been extensively
      studied, less is known about bovine IL-2. In order to understand the induction of
      bovine IL-2 at the molecular level, we have examined IL-2 mRNA induction. The
      dose-responses and time courses of the production of IL-2 mRNA in response to
      Concanavalin A (ConA), 12-O-tetradecanoylphorbol-13-acetate (TPA), and ionomycin
      in lymph node lymphocytes (LNC) were determined. We found that high levels of IL
      2 mRNA were produced in response to 1 microgram ml-1 ConA plus 10(-8) M TPA, but
      that even higher levels were produced in response to 1 microM ionomycin plus 10(
      8) M TPA. We also found that LNC stimulated with ConA displayed two phases of IL
      2 mRNA production, one occurring approximately 2-4 h after stimulation and one
      occurring approximately 10 h after stimulation. However, in the presence of ConA
      plus TPA or ionomycin plus TPA the response was monophasic. IL-2 mRNA was
      detected within 2 h of addition of ConA plus TPA (the earliest time examined),
      reached maximum levels within 6 h, and declined to low levels after 12 h. IL-2
      mRNA from LNC incubated with ionomycin plus TPA appeared within 2 h, and reached
      maximum levels at about 9 h. In contrast to the decrease seen after 12 h with
      ConA plus TPA, IL-2 mRNA from these cells remained high for 18 h and declined to
      low levels after 24 h.

PMID- 1372138
TI  - Replication of adeno-associated virus type 2 in human lymphocytic cells and
      interaction with HIV-1.
AB  - Adeno-associated virus (AAV) is a nonpathogenic parvovirus which normally
      requires helper adenovirus or herpes-virus for replication. We examined the
      growth of AAV type 2 in human lymphocytes and its possible interaction with HIV
      1. Three B cell lines (CK-B, HS-2, and UC729) and four T cell lines (Molt-4,
      Jurkat, HUT78, and HUT78+HIV, which is persistently infected with HIV-1) were
      infected with AAV either in the presence or in the absence of adenovirus. AAV DNA
      was found in cells of all the lines following incubation with the virus,
      indicating absorption. AAV DNA replication occurred in most cell lines without
      particular preference for B or T cells, but only in the presence of helper virus,
      either adenovirus or Epstein-Barr virus. Expression of AAV proteins was examined
      by immunoblotting and ELISA, using sera specific for AAV Rep or capsid proteins.
      The level of AAV protein synthesis correlated with the efficiency of AAV DNA
      replication, and both varied between cell lines. The yield of infectious AAV was
      low in most cases, except in one T4 line (Jurkat), where AAV replication and
      protein synthesis in the presence of adenovirus were very extensive. In HUT78+HIV
      cells both adenovirus and AAV (in the presence of Ad2) replicated efficiently.
      The effects of adenovirus plus AAV coinfections on HIV-1 replication, measured by
      reverse-transcriptase (RT) activity, were mild. Infection with adenovirus or AAV
      alone resulted in a 60-70% increase in RT activity, while infection with AAV plus
      adenovirus resulted in a 20% decrease in RT activity. The yield of infectious AAV
      in this cell line was very low.

PMID- 1372139
TI  - Mapping of the antigenic determinants recognized by monoclonal antibodies against
      the M2 protein of rabies virus.
AB  - Twenty-one hybridomas producing monoclonal antibodies (moAbs) against the M2
      protein of the Nishigahara (RECH) strain of rabies virus were prepared using the
      SDS-polyacrylamide gel-purified M2 protein as the immunogen. All moAbs reacted
      with the protein after Western blotting of rabies virus. By combinations of
      competitive binding assays, examination of the reactivity of moAbs to the cells
      infected with parent RCEH and two other strains, CVS and HEP-Flury, and
      immunoprecipitation with in vitro translation products derived from full-length
      and truncated cDNAs of the M2 gene, these moAbs could be classified into seven
      epitope groups. Of these, 20 moAbs belonging to six epitope groups were suggested
      to recognize an antigenic determinant in the amino-terminal region, from the 1st
      to the 72nd amino acid of the protein (8 moAbs from two groups directed to amino
      acids 1 to 72; 2 moAbs from a group directed to amino acids 9 to 72; 5 moAbs from
      a group directed to amino acids 17-72; 5 moAbs from two groups directed to amino
      acids 32 to 72). The antigenic determinant recognized by the remaining 1 moAb was
      shown to be located in the amino acid region from 50 to 171. These moAbs should
      be useful for further studies on the biological functions of the M2 protein of
      rabies virus.

PMID- 1372140
TI  - Use of recombinant fusion proteins and monoclonal antibodies to define linear and
      discontinuous antigenic sites on the dengue virus envelope glycoprotein.
AB  - Sixteen overlapping fragments of the dengue-2 virus envelope (E) protein,
      expressed as trpE-E fusion products in Escherichia coli, were used to map the
      epitopes defined by a panel of 20 monoclonal antibodies (MAbs) by immunoblotting.
      Using this technique, the amino acid sequence of six antigenic domains on the E
      protein was characterized. Nonneutralizing MAbs were found to define either
      linear-specific, subcomplex-specific (amino acids 22-58), and complex-specific
      (amino acids 304-332) epitopes or a subcomplex conformational-dependent epitope
      requiring the presence of two closely linked amino acid sequences from the E
      protein, 60-97 and 298-397. Neutralizing MAbs, however, defined either group
      reactive epitopes present on two overlapping domains (amino acids 60-135; amino
      acids 60-205) or type-, subcomplex-, complex-, subgroup-, and group-specific
      determinants (amino acids 298-397). These neutralizing epitopes were all found to
      be dependent upon disulfide bridges. Our results suggest that the maintenance of
      a topographical arrangement of discontinuous antigenic domains in the flavivirus
      E-protein is necessary to induce neutralizing and protective antibodies.

PMID- 1372141
TI  - Efficient replication and expression of murine leukemia virus with major
      deletions in the enhancer region of U3.
AB  - The effect of deletions within the enhancer region in the U3 part of the LTR
      derived from the murine retrovirus Akv was studied. The deletions were stably
      transmitted through normal virus replication as shown by sequence analysis of
      cloned polymerase chain reaction product of the cDNA copy of the viral RNA.
      Genetic tagging of the retrovirus with lacO facilitated the analysis. Among the
      individual mutated LTRs an over 100-fold difference in a transient expression
      assay was previously detected. This difference was not revealed in studies of
      viral replication in cell culture, where the expression level of virus with the
      deleted LTRs all reached the level of virus with the intact LTR. We propose that
      stimulatory cis-acting sequences either adjacent to the site of proviral
      integration or in the coding regions of the provirus may compensate for deletions
      in the LTR.

PMID- 1372142
TI  - Immunological analysis of human immunodeficiency virus type 1 envelope
      glycoprotein proteolytic cleavage.
AB  - Two potential cleavage sites have been identified on precursor gp 160 of human
      immunodeficiency virus type 1. Using antibodies directed against the C-terminus
      of gp 120, including the sequence between the two sites, we have shown that
      nonmutated viral and recombinant gp 160 are cleaved at both sites: the great
      majority of molecules are cleaved at site 1 (Arg-Glu-Lys-Arg), and gp41 can then
      associate as an oligomer; a minority of molecules are cleaved at site 2 (Lys-Ala
      Lys-Arg-Arg) and the corresponding gp41 appears to present as a monomer. This
      could reflect two different processing pathways for gp41 biosynthesis, one of
      which only may result in biologically active molecules according to the
      literature.

PMID- 1372143
TI  - [A case of vitello intestinal cyst].
AB  - A case of vitello intestinal cyst was reported. A 16-month-old girl was referred
      to our clinic with a complaint of a cystic mass in the region of the navel. With
      a diagnosis of urachal cyst, resection of the cyst was performed.
      Histopathologically, the cyst wall consisted of fibrous and fat tissue, and a
      small polypoid tumor which was found on the inner surface of the cyst was covered
      by intestinal epithelia. Pancreatic and gastric mucosal elements were observed in
      the submucosal layer. The histopathological diagnosis was vitello intestinal
      cyst. Serum amylase level elevated preoperatively normalized after removal of the
      cyst. We collected 11 cases of vitello intestinal cyst reported in Japan
      including the present case. Ectopic pancreatic tissue is considered a
      characteristic of vitello intestinal cyst and that serum or fluid amylase level
      may be useful for differential diagnosis of the disease.

PMID- 1372144
TI  - Evidence of increased microvascular resistance and arteriolar hyalinosis in skin
      in congestive heart failure secondary to idiopathic dilated cardiomyopathy.
AB  - Does nervous microvascular stress from backward cardiac failure and abnormal
      baroreceptor-mediated vasodilation in the upright position alter the
      microvascular resistance and structure of the resistance vessels with time? The
      minimal vascular resistance and structure of the terminal arterioles were
      measured in skin at the dorsum of the foot in 14 healthy subjects, in 12 patients
      with short-term congestive heart failure (CHF) (New York Heart Association
      functional class greater than or equal to II for less than 1 year), and in 14
      with long-term CHF (New York Heart Association functional class greater than or
      equal to II for greater than 1 year). Blood flow was measured by the local
      technetium-99m-pertechnetate washout method in a vascular bed paralyzed by
      histamine before, during and after 3 to 5 stepwise increases of external counter
      pressure. Minimal vascular resistance was calculated from the relation between
      blood flow and applied pressure. Minimal vascular resistance was significantly
      increased in both short-term (9.0 +/- 1.9 mm Hg.ml-1.100 g.min; p = 0.0003) and
      long-term (9.1 +/- 3.6 mm Hg.ml-1.100 g.min; p = 0.008) CHF patients compared
      with that in healthy control subjects (6.0 +/- 1.7 mm Hg.ml-1.100 g.min).
      Structural microangiopathy (increased hyalinosis of the basement membranes in the
      terminal arterioles) was found in skin biopsies in 21 of 24 patients with CHF in
      whom biopsies were obtained, but in none of the 14 control subjects (p less than
      0.002). Multiple regression analysis demonstrated a weak but significant direct
      association between minimal vascular resistance and the degree of structural
      microangiopathy (p less than 0.03; r = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372145
TI  - T-cell lymphoma and the virus-associated hemophagocytic syndrome.
AB  - A 20-month-old girl had a disorder that by both clinical and histologic criteria
      resembled the virus-associated hemophagocytic syndrome in the setting of Epstein
      Barr virus infection. Subsequent investigation revealed histologic evidence of
      disseminated T-cell lymphoma. DNA hybridization studies displayed a monoclonal T
      cell receptor beta chain rearrangement, in the absence of clonal immunoglobulin
      gene rearrangement, and a single band in the analysis for the fused termini of
      the Epstein-Barr virus genome. These results suggest the presence of a monoclonal
      population of T lymphocytes infected with Epstein-Barr virus. The diagnosis of
      lymphoma was confirmed at autopsy. The authors discuss the association of Epstein
      Barr virus infection with the development of T-cell lymphoma and propose that the
      previous reports of virus-associated hemophagocytic syndrome include cases of
      unrecognized T-cell lymphoma.

PMID- 1372146
TI  - Peripheral airway cell marker expression in non-small cell lung carcinoma.
      Association with distinct clinicopathologic features.
AB  - Paraffin sections of 247 primary and metastatic non-small cell lung carcinomas,
      the corresponding non-neoplastic lungs, and 75 other specimens were examined by
      immunohistochemical procedures using a panel of antibodies against the specific
      products of peripheral airway cells: the major surfactant-associated protein and
      10-kD Clara cell protein. Non-small cell lung carcinoma tumors most frequently
      positive for either peripheral airway cell marker were adenocarcinomas (41%),
      especially those with papillolepidic growth pattern (56%), followed by large cell
      carcinomas (25%), other adenocarcinomas (22%), and squamous cell carcinomas
      (16%). Immunoreactivity was mainly focal and the expression of the two peripheral
      airway cell markers was discordant. The incidence of marker expression was
      similar in metastatic and primary non-small cell lung carcinoma. Other organs and
      their tumors were negative, with few exceptions. Non-small cell lung carcinomas
      positive for peripheral airway cell markers were associated with younger age and
      less-intense smoking, and surfactant-associated protein reactivity was more
      common in women than in men. Peripheral airway cell markers were independent
      prognostic factors for survival and delayed development of metastases in patients
      with less-advanced disease. It is concluded that surfactant-associated protein
      and 10-kD Clara cell protein are specific markers for non-small cell lung
      carcinoma and peripheral airway cell differentiation and provide useful tools to
      study the pathogenesis, biology, and prognosis of non-small cell lung carcinoma.

PMID- 1372147
TI  - Amyloid localized to tenosynovium at carpal tunnel release. Immunohistochemical
      identification of amyloid type.
AB  - Thirty-five patients seen at the Mayo Clinic from 1968 to 1977 who had carpal
      tunnel syndrome and local deposition of amyloid without evidence of systemic
      amyloidosis were identified. The unlabeled immunoperoxidase method was used with
      antisera against purified amyloid proteins of the AA, A kappa, A lambda, AF/ASC1
      (prealbumin) (transthyretin), and AB (beta 2-microglobulin) types. In 33 of the
      35 patients, amyloid stained with antisera to transthyretin; in the remaining 2
      patients, the amyloid did not stain with any antisera. Nine of the 35 patients
      had a monoclonal protein in the serum, and 2 had a monoclonal light chain in the
      urine. Systemic amyloidosis or multiple myeloma did not develop in any of these
      11 patients. During follow-up, systemic amyloidosis developed in only 2 of the 35
      patients: 1 had senile systemic amyloidosis and 1 had tissue that was inadequate
      for immunohistochemical staining. Amyloid localized to the tenosynovium consists
      of transthyretin, and systemic amyloidosis rarely develops.

PMID- 1372148
TI  - Diagnosis of hairy leukoplakia by exfoliative cytologic methods.
AB  - The cytologic characteristics of hairy leukoplakia (HL) are described based on
      the findings observed in four lesions. All cases were confirmed by histologic
      study, and Epstein-Barr virus DNA was detected by means of in situ hybridization
      of tissue sections. All smears from the lesions exhibited a distinctive
      appearance and three types of epithelial changes were observed: (1) intranuclear
      inclusions of Cowdry type A, (2) intranuclear inclusions with a ground-glass
      appearance, and (3) clumping and margination of chromatin around the nuclear
      membrane. Other findings were the presence of bacterial colonies in all lesions
      and Candida organisms in three of them. The results of this study suggest that
      conventional exfoliative cytologic examination may prove to be a useful, simple,
      cost-effective, and reliable method to diagnose hairy leukoplakia.

PMID- 1372149
TI  - Spindle cell hemangioendothelioma exhibits the ultrastructural features of
      reactive vascular proliferation rather than of angiosarcoma.
AB  - A patient with spindle cell hemangioendotheliomas was followed from 1964 to the
      present time, allowing the authors the opportunity to examine the lesions in the
      early, mature, and old phases. Organizing thrombi of different stages associated
      with slit-like vascular proliferation were always observed, whereas cavernous
      vascular spaces predominated as the lesions became older. Each spindle cell
      hemangioendothelioma initially developed relatively rapidly and was sometimes
      painful but then persisted as a silent nodule for decades. Transmission and
      scanning electron microscopic studies revealed that endothelial cells tended to
      digitate into the slit-like proliferating channels, became attached to other
      cells by means of tight junctions, and thus obstructed the channels at sites
      where thrombi developed repeatedly. The vascular spaces, ranging in nature from
      slit-like to cavernous, were outlined further by a relatively sparse mantle of
      ramified or dendritic interstitial cells that corresponded to spindle cells. Most
      of the cells appeared simply to be fibroblasts, but they developed the features
      of pericytes when they were close to the endothelial lining of well-developed
      vascular lumens. Large vascular spaces and phleboliths were surrounded by smooth
      muscle cells. Approximately 20% of the interstitial cells were dendritic
      macrophages characterized by phagocytic activity, presence of many lysosomes, and
      Factor XIIIa expression. The long and characteristic clinical course, the
      histologic evidence that thrombosis and its organization was continually
      occurring within the lesions, and the ultrastructural finding that spindle cell
      hemangioendotheliomas were composed of different microvascular segments from
      capillaries to veins, suggest that spindle cell hemangioendotheliomas may develop
      from a cycle of recanalization after thrombosis that occurs repeatedly because of
      the unique endothelial growth that was noted. This is in contrast with the
      previous conception that they were low-grade angiosarcomas.

PMID- 1372150
TI  - Immunological evaluation of harvested stem cells obtained by leukapheresis after
      chemotherapy.
AB  - Some patients suffering from malignancies may benefit of myeloablative
      chemotherapy followed by hematological reconstitution with autologous peripheral
      blood reinfusion. A quick evaluation of the number of hematopoietic progenitors
      present in leukapheresis blood samples is necessary to ensure the collection of a
      sufficient number of these cells. A study was performed on a series of 25
      leukapheresis following initial chemotherapy. The number of granulomonocytic
      colony-forming unit (CFU-GM) and the number of CD34+ cells were evaluated
      simultaneously, in each sample. Results have shown a relatively strong linear
      correlation between both methods of evaluation of hematopoietic progenitors,
      suggesting that immunophenotyping could be a useful method to estimate the number
      of progenitors.

PMID- 1372151
TI  - Studies on the in vitro and in vivo expression of a dysfunctional alpha-globin
      gene.
AB  - In a black family with members having alpha-thalassemia and hemoglobin H (HbH)
      disease, a deletion of an AG dinucleotide at the 3' end of exon 1 near the
      junction with intron 1 was shown previously to produce a dysfunctional alpha
      thalassemia gene with a reading frame-shift and a nonsense codon (Safaya S,
      Rieder RF: J Biol Chem 263:4328-4332, 1988). We have found that the same mutation
      is responsible for alpha-thalassemia and HbH disease in a second unrelated black
      family (Bellevue R, Dosik H, Rieder RF: Br J Haematol 41:193-202, 1979). Despite
      the loss of two nucleotides from the consensus sequence at the 5' splice donor
      site of intron 1, studies employing an in vitro plasmid-based expression system
      indicated that the mutant alpha-globin mRNA was spliced normally and expressed in
      amounts equal to normal alpha-globin mRNA in COS-7 cells. The correct processing
      of the mRNA in these studies is probably due to the presence of a tandem repeat
      of the affected AG dinucleotide. However, in reticulocytes from subjects bearing
      the mutant gene, we were unable to detect any of the abnormal mRNA. These
      findings suggest that there is accelerated post-transcriptional loss of mRNA
      bearing a premature terminator codon.

PMID- 1372152
TI  - Serum lipase: a better test to diagnose acute alcoholic pancreatitis.
AB  - OBJECTIVE: To determine whether serum lipase is a better test than serum amylase
      to diagnose acute alcoholic pancreatitis. PATIENTS: Two hundred two asymptomatic
      chronic alcoholics (Group A) and 29 patients with image-proven pancreatitis
      (Group P). MEASUREMENTS: Serum lipase was measured using the Kodak Ektachem
      clinical chemistry slide. Serum amylase was estimated using the Kodak Ektachem
      clinical chemistry slide or the Beckman Astra amylase chemistry module. RESULTS:
      The level of serum amylase in Group A ranged from 17 to 347 U/L (mean 71, SD +/-
      36 U/L) and in Group P from 180 to 2,985 U/L (mean 722, SD +/- 663 U/L). Thirteen
      of 29 patients (45%) with image-proven pancreatitis had levels that overlapped
      those found in asymptomatic alcoholics. The serum lipase levels in Group A ranged
      from 34 to 600 U/L (mean 186, SD +/- 111 U/L), while in Group P, the
      corresponding figures were 1,011 to 25,706 U/L (mean 5,822, SD +/- 5,664 U/L).
      None of the 29 patients with image-proven pancreatitis had levels that overlapped
      those found in asymptomatic alcoholics. CONCLUSIONS: Serum lipase is a better
      test that serum amylase to diagnose acute alcoholic pancreatitis.

PMID- 1372153
TI  - Benefit of G-CSF for methotrexate-induced neutropenia in rheumatoid arthritis.

PMID- 1372154
TI  - Dual role of tumor necrosis factor-alpha in angiogenesis.
AB  - The role of tumor necrosis factor-alpha (TNF; cachectin) in angiogenesis has been
      controversial. In vitro TNF inhibits proliferation of endothelial cells (EC)
      whereas in the cornea it appears to stimulate vessel growth. The authors tested
      TNF in their recently developed disc angiogenesis system (DAS), designed to
      measure the proliferation of microvessels. The DAS, implanted subcutaneously in
      mice, was either fitted with a central pellet containing mouse recombinant TNF
      (mrTNF), or exposed to mrTNF delivered subcutaneously by an osmotic minipump. Low
      doses of mrTNF (0.01-1 ng) induced angiogenesis, which was maximum at 0.1 ng,
      whereas high doses (1, and 5 micrograms) inhibited it. Subcutaneous mrTNF
      delivered at the (high) rate of 15-60 ng/hr for 14 days inhibited angiogenesis.
      These results indicate bimodal, dose-dependent opposing effects and explain some
      of the in vitro versus in vivo paradoxical results. TNF (native or exogenous) may
      have opposing effects on microvessels of neoplasms and inflammatory reactions,
      depending on its local tissue concentrations.

PMID- 1372155
TI  - Intermediate filaments as differentiation markers of normal pancreas and pancreas
      cancer.
AB  - Expression of intermediate filaments (IF) is regulated during development and
      differentiation. The authors have studied the expression of vimentin and
      cytokeratins (CK) 4, 7, 8, 13, 18, 19 in normal pancreas, chronic pancreatitis,
      and pancreas cancer using monoclonal antibodies. Immunohistochemical assays were
      performed on fresh frozen tissue sections and on cultured pancreas cancer cells
      using the streptavidin-peroxidase method. In normal pancreas, acinar cells
      expressed CK 8 and 18, whereas ductal cells expressed CK 7, 8, 18, and 19. CK 4
      was expressed by 5-10% of pancreas duct cells in all specimens of normal
      pancreas. CK 13 was not detected in any epithelial cells of normal pancreas or
      pancreatitis. CK 7, 8, 18, and 19 were homogeneously expressed in all pancreas
      cancers, whereas CK 4 was expressed only in 5-50% of cells in 10/16 tumors. Foci
      of squamous metaplasia expressed CK 13 but showed partial loss of expression of
      CK 7, 8, 18, and 19. Thirteen pancreas cancer cell lines examined showed
      homogeneous expression of CK 7, 8, 18, and 19; 2/11 lines expressed CK 4 weakly,
      and 6/11 expressed vimentin. CK 13 was not detected in any of the lines. These
      results indicate that pancreas cancer cells consistently express cytokeratin
      polypeptides characteristic of ductal epithelial cells and that this phenotype is
      retained in pancreas cancer cell lines. In addition, squamous metaplasia is
      associated with a coordinate change in the expression of CK polypeptides.

PMID- 1372156
TI  - Basal-cell keratins in cervical reserve cells and a comparison to their
      expression in cervical intraepithelial neoplasia.
AB  - Expression of keratins 5, 14 and 17 in endocervical subcolumnar reserve cells was
      detected by means of immunohistochemical studies using polypeptide specific
      monoclonal antibodies. These particular keratins that were found among others in
      basal cells could also be detected to a variable extent in metaplastic and
      dysplastic cervical lesions. In some cases of immature squamous metaplasia all
      three keratin subtypes were expressed throughout the full thickness of the
      epithelium. In contrast, in mature squamous metaplasia a compartmentalization of
      these keratins was observed. Mature squamous metaplastic epithelium showed a
      keratin distribution pattern comparable to ectocervical squamous epithelium, with
      the exception of keratin 17, which was only sporadically found in the basal layer
      of ectocervical epithelium and was always present in the basal cells of mature
      squamous metaplastic epithelium. During progression of cervical intraepithelial
      neoplasia a clear increase in the expression of keratin 17 was observed. However,
      also keratins 5 and 14 were expressed. Our results demonstrate that a
      considerable number of premalignant lesions of the uterine cervix express the
      same keratins as found in the progenitor reserve cells. Lesions that lack
      expression of keratin 17 may form a distinct group, which are regressive in
      nature and do not progress into cervical cancer.

PMID- 1372157
TI  - Immunohistochemical evidence of oxidative [corrected] stress in Alzheimer's
      disease.
AB  - Membrane and cytoskeletal structures are known targets of oxidative injury.
      Brains from patients with Alzheimer's disease have cytoskeletal abnormalities and
      platelet and possible neuronal membrane lesions. The authors have recently
      demonstrated that superoxide anion is a powerful inducer of heat-shock protein
      synthesis, and have also shown that in response to oxidative stress or
      hyperthermia, intracellular levels of antioxidant enzymes increase to several
      folds. Whether the aforementioned mechanisms play a role in Alzheimer's disease
      has been suggested but is not totally established. While exploring this
      possibility, tissue sections from five brains with Alzheimer's disease and five
      neuropathologically normal age-matched controls were immunostained with
      polyclonal antibodies against superoxide dismutase (CuZn- and Mn- forms) and
      catalase. A standard avidin-biotin-peroxidase method was used for antigen
      detection. A subgroup of neurofibrillary tangles (15-25%) and senile plaques
      (50%) showed immunoreactivity for both enzymes with a staining pattern similar
      (but not identical) to that usually observed with antibodies against ubiquitin.
      Senile plaques displayed a granular pattern of immunostaining. Amyloid cores in
      mature classical plaques remained unstained. In addition, occasional elements
      with features consistent with reactive glial cells were strongly immunostained.
      Tangle-free neurons in both diseased and control brains showed weak to absent
      intracytoplasmic immunoreactivity. The immunoreactivity was totally abolished by
      preincubation of the primary antibodies with the corresponding purified antigens.
      These findings support the hypothesis that oxidative stress may be involved in
      the pathogenesis of Alzheimer's disease.

PMID- 1372158
TI  - Expression of platelet-derived growth factor and its receptors in proliferative
      disorders of fibroblastic origin.
AB  - Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of
      connective tissue-derived cells in vitro. Less is known about its functions in
      vivo, and the role of PDGF in the development of human tumors has not been
      clarified. The authors have investigated the occurrence of PDGF and PDGF
      receptors in a series of proliferative disorders of fibroblastic origin using
      immunohistochemical and in situ hybridization techniques. High expression of PDGF
      beta-receptor mRNA and protein was found in the malignant tumors, and also in
      some benign lesions, such as dermatofibroma. In all these cases, benign as well
      as malignant, the PDGF B-chain mRNA, and less clearly, the PDGF A-chain mRNA,
      were coexpressed with the beta-receptor. In contrast, high expression of PDGF
      alpha-receptor mRNA was only found in fully malignant lesions, i.e., malignant
      fibrous histiocytoma. These data indicate that an autocrine growth stimulation
      via the PDGF beta-receptor could occur in an early phase of tumorigenesis, and
      may be a necessary but insufficient event for the progression into fully
      malignant human connective tissue lesions.

PMID- 1372159
TI  - Biologic and immunohistochemical analysis of interleukin-6 expression in vivo.
      Constitutive and induced expression in murine polymorphonuclear and mononuclear
      phagocytes.
AB  - Interleukin-6 (IL-6) is considered an important multifunctional cytokine involved
      in the regulation of a variety of cellular responses, including the induction of
      acute-phase protein synthesis, lymphocyte activation, and hematopoiesis. In vitro
      studies have identified many cells that can produce IL-6, but the cellular
      sources under physiologic conditions have yet to be identified. Using
      immunoaffinity purified goat anti-murine IL-6, the authors performed
      immunohistochemical studies to localize cells expressing IL-6 in selected organs
      of normal and endotoxin challenged NIH-Swiss outbred mice. In the blood, findings
      were correlated with cell-associated bioactivity using the standard B9 cell
      proliferation assay. In normal mice, constitutive expression was seen in
      granulocytes, monocytes and their precursors as well as in bone marrow and
      splenic stromal macrophages. Hepatic macrophages were negative, as were
      lymphocytes, megakaryocytes, erythroid precursors, and endothelial cells. In the
      absence of significant serum levels of IL-6, cell-associated IL-6 bioactivity was
      detected in circulating polymorphonuclear leukocytes (PMNs), but not lymphocytes.
      After endotoxin challenge, there was a threefold increase in PMN IL-6 content
      from 1 to 3 hours followed by almost complete depletion at 6 hours. This
      correlated well with a threefold increase of IL-6 mRNA in the bone marrow
      followed by a decrease at 6 hours. This pattern also correlated with serum levels
      of IL-6, which peaked at 3 hours and dropped significantly by 6 hours. By 24
      hours, cell-associated IL-6 showed recovery with no increase in serum levels. In
      vivo findings showing IL-6 expression in bone marrow macrophages support in vitro
      studies suggesting a role for IL-6 in hematopoiesis. Furthermore, PMNs as well as
      macrophages are likely important sources of IL-6 during inflammatory and septic
      states.

PMID- 1372160
TI  - Expression of intercellular adhesion molecule-1 in atherosclerotic plaques.
AB  - Immunohistochemistry of human atherosclerotic arteries demonstrates expression of
      the intercellular adhesion molecule-1 (ICAM-1) on endothelial cells, macrophages,
      and smooth muscle cells of the plaques. Normal arterial endothelial cells and
      intimal smooth muscle outside plaques give weaker or negative reactions; these
      differ from the strong endothelial expression in small vessels. Quantitative
      color-image analysis of the endothelial layer shows increased expression of ICAM
      1 in all subtypes of atherosclerotic lesions, except fibrous plaques. Endothelial
      expression of ICAM-1 may be involved in the recruitment of monocytes to the
      lesion, as suggested by its role in the entry of leukocytes, including monocytes,
      into foci of inflammation. Collaboration with other mechanisms, particularly
      chemoattractant factors, may be important for this effect. ICAM-1 enhanced
      monocyte recruitment is a potential mechanism for the growth of an
      atherosclerotic plaque.

PMID- 1372162
TI  - Vitronectin and its relationship to other extracellular matrix components in
      bronchoalveolar lavage fluid in sarcoidosis.
AB  - There is a need to find markers that can be used as indicators of early fibrotic
      changes in the lung in patients with sarcoidosis. The fibrotic reaction is
      accompanied by an increase in the connective tissue components, and the
      extracellular matrix molecules are characterized by an ability to interact with
      each other. We found increased concentrations of three components of the
      extracellular matrix, vitronectin (VN), fibronectin (FN), and hyaluronan (HA), in
      bronchoalveolar lavage (BAL) fluid from 56 patients with sarcoidosis compared
      with 38 healthy control subjects (p less than 0.001 for all). Using an enzyme
      linked immunosorbent assay, the median value for VN in BAL fluid from sarcoid
      patients was 74 micrograms/L (interquartile range, 47 to 138) compared with 38
      micrograms/L (IQR, 22 to 55) in control subjects. The median VN concentration in
      serum was 0.25 g/L in both groups. VN consists of various functional domains, and
      it may, together with FN and HA, contribute to repair or exaggeration of the
      interstitial changes that occur when sarcoidosis affects the lungs. VN correlated
      to the concentration of albumin in the BAL fluid (p less than 0.01) but even
      closer to the concentrations of FN and HA (p less than 0.001 for both). The
      extracellular matrix components did not show any correlation to the disease
      activity, roentgenographic stage, or functional signs of developed fibrosis. In
      conclusion, the increased concentrations of VN, FN, and HA may predict only an
      ongoing inflammation and not necessarily a fibrotic process.

PMID- 1372161
TI  - c-myc protein distribution. Neoplastic tissues of the human colon.
AB  - There is an extensive literature documenting the increased or deregulated
      expression of the c-myc oncogene in human malignancies. The authors have recently
      devised a sensitive immunocytochemical method for studying the tissue
      localization of c-myc protein in tissue sections of human colon. We have compared
      nuclear c-myc staining using a polyclonal rabbit anti-c-myc antibody and a mouse
      monoclonal myc antibody NCM II 274. Microscopic observation of the tissue
      specific pattern of c-myc protein distribution shows that nuclear staining
      intensity varies in normal and neoplastic crypt cell nuclei in parallel with
      morphologic criteria of neoplasia. These studies yield further information on the
      usefulness of c-myc protein as a prognostic indicator.

PMID- 1372163
TI  - Administration of alpha 1-proteinase inhibitor ameliorates bleomycin-induced
      pulmonary fibrosis in hamsters.
AB  - The effect of alpha 1-proteinase inhibitor (alpha 1Pi) administration on the
      acute lung injury and subsequent fibrosis induced by bleomycin (BLM) was examined
      in hamsters. Pulmonary lesions were quantitatively reduced in alpha 1Pi
      administered BLM-treated (BLM-alpha 1Pi) animals compared with animals treated by
      BLM alone (BLM-control) at both 7 days (acute stage) and 30 days (fibrotic stage)
      after BLM treatment. Analysis of intraalveolar cells from bronchoalveolar lavage
      (BAL) fluid revealed that neutrophils and lymphocytes were significantly
      decreased in the BLM-alpha 1Pi animals at 7 days after BLM treatment and that 30
      days after BLM treatment macrophages as well as neutrophils and lymphocytes were
      remarkably decreased in the BLM-alpha 1Pi animals. The elastase activity in
      supernatants of BAL fluid during 7 days following BLM treatment was detected, but
      there was no difference between the two groups. In vitro studies on neutrophil
      responsiveness to stimulation of BAL fluid at 3 days after BLM treatment revealed
      noticeable chemotaxis and generation of superoxide anion of isolated neutrophils,
      but alpha 1Pi did not show any inhibitory effects on neutrophil responsiveness.
      We suggest that alpha 1Pi administration ameliorates pulmonary fibrosis preceded
      by acute lung injury induced by BLM treatment in hamsters and that the inhibitory
      effects of alpha 1Pi on lung injury may not be brought about by altered elastase
      activity, chemotaxis, or superoxide generation in neutrophils. Alternative
      mechanisms are discussed.

PMID- 1372164
TI  - Isolation and characterization of the complement-inhibiting protein CD59 antigen
      from platelet membranes.
AB  - Several groups have recently described the isolation of a 20 kDa membrane-attack
      complex (MAC)-inhibiting protein, termed 'CD59 antigen', from human erythrocyte
      membranes. Antibodies raised against erythrocyte CD59 antigen detect antigen on
      the surface of many other cell types, and in some of these cells the antigen has
      been shown to have a molecular mass similar to that of the erythrocyte protein
      and to confer resistance to lysis by the MAC. A platelet-membrane form of CD59
      antigen has been described and reported to be much larger than the erythrocyte
      protein. Here I report the isolation of CD59 antigen from platelet membranes and
      its molecular and functional characterization. The platelet protein is not
      significantly larger than the erythrocyte form and possesses similar MAC
      inhibiting activity. Platelet CD59 antigen is anchored to the membrane via a
      glycosyl-phosphatidylinositol link, and consequently it is suggested that
      deficiency of this protein might be responsible for the increased thrombotic
      tendency observed in paroxysmal nocturnal haemoglobinuria.

PMID- 1372165
TI  - Association of tetrapyrrole intermediates in the bacteriochlorophyll a
      biosynthetic pathway with the major outer-membrane porin protein of Rhodobacter
      capsulatus.
AB  - Rhodobacter capsulatus regulates synthesis of bacteriochlorophyll a in response
      to changes in oxygen partial pressure and light intensity. One early model
      proposed that this regulation involved a carrier polypeptide that functions to
      tether tetrapyrrole intermediates to the membrane. In the present study we
      isolated tetrapyrrole intermediates accumulated in three strains of R. capsulatus
      that contain mutations which block bacteriochlorophyll a biosynthesis at
      different steps of the magnesium branch of the pathway. Each of the tetrapyrrole
      intermediates was shown to be associated with the same 32 kDa polypeptide, as
      indicated by similar electrophoretic mobility and antigenic cross-reactivity with
      polyclonal antisera. The 32 kDa pigment-associated protein was further found to
      have an electrophoretic mobility, antigenic cross-reactivity and N-terminal
      sequence identical with those of the previously characterized major outer
      membrane porin protein of R. capsulatus.

PMID- 1372166
TI  - Epitope map of two polyclonal antibodies that recognize amyloid lesions in
      patients with Alzheimer's disease.
AB  - Two synthetic peptides with sequences identical with those of fragments of the
      extracellular domain of the Alzheimer's-disease amyloid precursor protein (APP)
      were used to raise antibodies. SP28 comprises positions 597-624 of the APP695
      isoform, whereas SP41 extends towards the N-terminus (amino acids 584-624) and
      contains the entire SP28 peptide. Using e.l.i.s.a. and inhibition experiments we
      identified the two beta-turn-containing segments 602-607 and 617-624 as the
      epitopes recognized by anti-SP41 and anti-SP28 respectively. Both antibodies
      immunolabelled amyloid lesions in brains from Alzheimer's-disease patients and
      patients with related disorders, whereas they were unreactive in control brains.
      However, when probed on immunoblots, anti-SP28 failed to detect full-length APP
      from baculovirus-infected Sf9 cells, and anti-SP41 reacted weakly compared with
      other anti-APP antisera. The data suggest that these antibodies are directed to
      conformational epitopes not existent in the native molecules but present after
      alternative APP processing.

PMID- 1372169
TI  - Characterization of cDNA and genomic sequences encoding rabbit ELAM-1:
      conservation of structure and functional interactions with leukocytes.
AB  - Endothelial leukocyte adhesion molecule-1 (ELAM-1) is a cytokine-inducible
      endothelial cell surface glycoprotein involved in the adherence of neutrophils.
      ELAM-1 belongs to the selectin family of cell-surface molecules characterized by
      the general structure of an amino-terminal lectin domain followed by an epidermal
      growth factor domain, a variable number of complement regulatory elements, a
      single transmembrane sequence, and a short cytoplasmic tail. To study the in vivo
      regulation and expression of ELAM-1, we have isolated a complementary DNA (cDNA)
      clone encoding the rabbit homolog of human ELAM-1. The nucleotide sequence of the
      rabbit cDNA as well as its deduced amino acid sequence display extensive
      conservation compared to the human sequences. Rabbit ELAM-1 contains the
      characteristic protein domain organization of the selectin gene family and shares
      74% amino acid identity with its human counterpart. However, rabbit ELAM-1
      contains five complement regulatory elements whereas the human protein has six of
      these elements. Characterization of the genomic sequence encoding rabbit ELAM-1
      indicated that individual extracellular protein domains are encoded by distinct
      exons. The genomic organization of rabbit ELAM-1 parallels that found for the
      human ELAM-1 gene and is similar to the pattern observed for other selectin
      family members (GMP-140, Lam-1), consistent with the hypothesis that the
      selectins evolved by duplication and rearrangement of individual exons. COS cells
      transiently expressing the rabbit ELAM-1 cDNA mediate the adhesion of rabbit and
      human polymorphonuclear leukocytes and are recognized by antibodies prepared
      against the human protein. Our results suggest that the specificity of molecular
      interaction between ELAM-1 and its ligand is highly conserved.

PMID- 1372167
TI  - Natural polyamines stimulate G-proteins.
AB  - The natural polyamines spermine and spermidine, the biosynthetic precursor
      putrescine and their analogues cadaverine and tyramine stimulate the GTPase
      activity of purified GTP-binding proteins (Go/Gi) from calf brain reconstituted
      into phospholipid vesicles. The order of potency was spermine greater than
      spermidine greater than putrescine = cadaverine greater than tyramine. The
      physiological relevance of this observation was assessed, showing the same order
      of potency of polyamines in the stimulation of peritoneal and tracheal rat mast
      cells. The activation of rat mast cells by polyamines was inhibited by
      benzalkonium chloride or by a 2 h pretreatment of the cells with pertussis toxin.
      The increase in inositol phosphates evoked by polyamines was also inhibited by
      pertussis toxin. Therefore we propose that intracellular polyamines might control
      the basal level of second messengers and modulate extracellular signals
      transduced through G-protein-coupled receptors.

PMID- 1372168
TI  - Molecular cloning and nucleotide sequence of a cDNA encoding hydroxyindole O
      methyltransferase from chicken pineal gland.
AB  - Hydroxyindole O-methyltransferase (EC 2.1.1.4) is the enzyme that catalyses the
      synthesis of melatonin in the pineal gland and in the retina. Polyadenylated RNA
      from chicken pineal glands was used to prepare a cDNA library in lambda gt11. The
      library was screened with an antiserum directed against chicken hydroxyindole O
      methyltransferase, and one cDNA clone was isolated. The fusion protein expressed
      by phage lysogens was identified on Western blots as a 165 kDA immunoreactive
      protein (beta-galactosidase, 110 kDa; hydroxyindole O-methyltransferase, 38 kDa).
      The fusion protein exhibited hydroxyindole O-methyltransferase activity. Its Km
      values for N-acetyl-5-hydroxytryptamine and S-adenosylmethionine were 5 times
      those of the natural enzyme. The intrinsic activity of the fusion protein was
      approx. 0.25% that of the natural enzyme. The cDNA consisted of 1436 nucleotides,
      including a 1038-nucleotide sequence encoding a full-length 346-amino-acid
      hydroxyindole O-methyltransferase. Comparison with bovine hydroxyindole O
      methyltransferase [Ishida, Obinata & Deguchi (1987) J. Biol. Chem. 262, 2895
      2899] revealed 52% identity in nucleotide sequences and 44% identity in peptide
      sequences. Northern-blot analysis revealed the presence of hydroxyindole O
      methyltransferase mRNA transcripts in chicken pineal gland and retina, but not in
      the telencephalon.

PMID- 1372170
TI  - [The biological aftereffects of preoperative and palliative percutaneous biliary
      drainage].
AB  - Biological repercussions in 78 patients with malignant obstructive jaundice in
      whom percutaneous biliary drainage was performed, are reported. In 37 cases
      drainage was done during operation while 41 were palliative. Biochemistry,
      proteinogram, hematological studies, renal function and immunology were assessed
      15.7 +/- 3.4 days postoperatively and 25.2 +/- 4.7 days in palliative drainage.
      Results show a significant improvement of all parameters, more important in
      preoperative drainages especially in those combining percutaneous and internal
      drainage techniques.

PMID- 1372171
TI  - [Whipple's disease: the diagnostic and therapeutic considerations].

PMID- 1372172
TI  - [The spontaneous regression of a hepatocellular carcinoma].

PMID- 1372173
TI  - Intergeniculate leaflet and suprachiasmatic nucleus organization and connections
      in the golden hamster.
AB  - The intergeniculate leaflet (IGL) is a distinct subdivision of the lateral
      geniculate complex which receives retinal input and projects upon a circadian
      pacemaker, the suprachiasmatic nucleus (SCN). In the present study, we have
      analyzed the organization of the IGL and its connections in the hamster, a
      species commonly used in circadian rhythm studies. The location of the IGL is
      defined by the presence of retinal afferents demonstrated by anterograde
      transport of cholera toxin-HRP, neuropeptide Y-containing neurons and axons,
      cells retrogradely labeled from the regions of the SCN and contralateral IGL, and
      substance P-containing axons. It is a long nucleus extending the entire
      rostrocaudal axis of the geniculate. The most rostral IGL lies between the
      lateral dorsal thalamus, ventrolateral part, and the horizontal cerebral fissure.
      It then enlarges ventral to the rostral dorsal lateral geniculate, medial to the
      optic tract. The mid-portion of the leaflet is a thin lamina intercalated between
      the dorsal and ventral geniculate nuclei. The extended caudal portion of the
      nucleus lies lateral and ventral to the medial geniculate and is contiguous with
      the zona incerta and the lateral terminal nucleus. The IGL contains populations
      of neuropeptide Y (NPY+) and enkephalin (ENK+) neurons which project to the
      retinorecipient portion of the SCN. In addition to the immunoreactive perikarya,
      the IGL contains plexuses of NPY+, ENK+, substance P-, serotonin-, and glutamic
      acid decarboxylase-immunoreactive axons. Retrograde transport studies demonstrate
      that, in addition to the NPY+ neurons, there is a population of non-NPY+ neurons
      projecting upon the SCN.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372174
TI  - Organization and development of horizontal cells in the goldfish retina, II: Use
      of monoclonal antibody MH1.
AB  - We have produced and characterized a monoclonal antibody, MH1, which selectively
      labels rod horizontal cells and Muller cells in the goldfish retina. Biochemical
      and tissue distribution studies indicate that MH1 may recognize four out of five
      classes of intermediate filament proteins in goldfish: vimentin, desmin, glial
      fibrillary acidic protein (GFAP), and keratin, but not neurofilament. The
      intermediate filament which is labeled strongest in the retina is vimentin. In
      the goldfish retina, the only type of horizontal cells recognized by MH1 appear
      to be rod horizontal cells. This result suggests that the rod horizontal cell, an
      interneuron, and Muller (glial) cells share a common antigen: vimentin, which is
      usually only expressed in mesenchymal origin cells. The development of rod
      horizontal cells in the goldfish retina was also studied using MH1. The cells
      were not labeled by MH1 until 4-6 weeks posthatching, a stage in which the
      animals are already visually active. MH1 also did not label any horizontal cell
      in the region close to the ora terminalis in the goldfish retina. These results
      suggest that either the emergence and maturation of rod horizontal cells occur
      late during goldfish retinal development or the expression of vimentin itself
      occurs late in the development of rod horizontal cells.

PMID- 1372175
TI  - The laminar distribution of macaque tectobulbar and tectospinal neurons.
AB  - The superior colliculus exerts its most direct influence over orienting
      movements, and saccades in particular, via its descending projections to the
      brain stem and spinal cord. However, while there is detailed physiological data
      concerning the generation of saccade-related activity in the primate superior
      colliculus, there is relatively little data on the detailed connectivity of this
      structure in primates. Consequently, retrograde transport techniques were
      utilized to determine the locations of the cells of origin of these descending
      pathways in macaque monkeys. Tectal cells that projected to the ipsilateral
      pontine reticular formation were mainly found in the deep gray layer and
      occasionally in the intermediate gray layer. Tectal cells that projected to the
      contralateral pontine reticular formation were predominantly located in the
      intermediate gray layer. The contralaterally projecting population could be
      subdivided into two groups. The cells in upper sublamina of the intermediate gray
      layer project primarily to the saccade-related regions of the paramedian
      reticular formation. Cells in the lower sublamina project primarily to more
      lateral regions of the pontine reticular formation and to the spinal cord. We
      conclude that the primate colliculus is provided with at least three descending
      output channels, which are likely to differ in their connections and functions.
      Specifically, it seems likely that the lower portion of the intermediate gray
      layer may be specialized to subserve combined head and eye orienting movements,
      while the upper sublamina subserves saccades.

PMID- 1372176
TI  - Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in
      pregnancies with insulin-dependent diabetes: implications for screening for
      Down's syndrome.
AB  - OBJECTIVE: To investigate maternal serum unconjugated oestriol (uE3) and human
      chorionic gonadotrophin (hCG) levels in pregnant women with insulin-dependent
      diabetes mellitus and to consider the implications of the results for antenatal
      screening for Down's syndrome. DESIGN: Descriptive study using stored antenatal
      serum samples. SETTING: Stored serum samples collected from women receiving
      routine antenatal care in Oxford. SUBJECTS: 126 singleton pregnancies in 92 women
      with insulin-dependent diabetes mellitus and for each pregnancy, two pregnancies
      without diabetes matched for gestational age and duration of storage of the serum
      sample. None of the pregnancies was associated with fetal neural tube defect or
      Down's syndrome. MAIN STUDY MEASURES: Maternal serum uE3 and hCG levels at 15-22
      weeks gestation. Alpha-fetoprotein (AFP) levels were also measured for
      comparison. RESULTS: The median uE3 level in the diabetic pregnancies was 0.92
      multiples of the median (MoM) for pregnancies without diabetes at the same
      gestational age (P less than 0.05); and the hCG level was 0.95 MoM (P = 0.48).
      The median AFP level was also reduced to 0.77 MoM (P less than 0.001).
      CONCLUSION: The reduction in uE3 and AFP levels in insulin-dependent diabetic
      pregnancies is sufficiently great to be taken into account in maternal serum
      screening programmes for Down's syndrome. Dividing the uE3 and AFP levels in such
      pregnancies by the corresponding median for insulin-dependent diabetic
      pregnancies will yield a similar false-positive rate in pregnancies with and
      without insulin-dependent diabetes mellitus.

PMID- 1372177
TI  - Effect of various blood-derived and semisynthetic nutrient media on in vitro
      uptake of 125I-albumin across the intact porcine aortic endothelial surface in an
      organ-support system.
AB  - The effects on porcine arterial structure and permeability of a 4-hour in vitro
      incubation at 37 degrees C in eight different blood-derived and synthetic
      nutrient media were examined. Changes in arterial permeability were inferred from
      the normalized, 1-hour, pressurized, transendothelial uptake (M/c0 cm) of porcine
      125I-albumin in 60 porcine aortic tissue preparations using an organ-support
      system. The organ-support system provided experimental control of ambient gas
      composition, temperature, transmural pressure, flow (stirring), and nutrient
      media at a number of sites along the vessel. Light and electron microscopic
      (scanning and transmission) structural correlations with the observed
      permeability changes were examined. The M/c0 from the autogenous serum (AS)
      medium was used as the "control" measurement in each vessel preparation. (Grand
      mean M/c0 for AS from all studies was 0.312 +/- 0.011 [x10(-3)] [mean +/- SEM]
      cm, n = 60.) For brevity, M/c0 values from the other media are expressed below as
      a percentage of the corresponding paired M/c0 from the AS. Uptake from
      heparinized autogenous blood was 113 +/- 9% of that from AS (p = 0.119); from
      heparinized autogenous plasma was 135 +/- 10% (p = 0.048); from AS+heparin was 97
      +/- 5% (p = 0.498); from pooled porcine serum was 113 +/- 9% (p = 0.037); from a
      synthetic medium was 131 +/- 8% (p = 0.004); and from a physiological hetastarch
      solution was 532 +/- 8% (p = 0.0002). Associated light microscopic structural
      changes and ultrastructural changes were not found. We conclude that 1)
      incubation with AS and heparinized blood (both of which are autogenous blood
      substances containing platelet products or platelets) provided the best support
      for the endothelial barrier function, whereas heparin plasma, pooled serum, a
      synthetic medium, and particularly hetastarch provided poorer support; 2)
      arterial permeability can increase significantly without discernible endothelial
      ultrastructural changes; and 3) AS and to a lesser extent heparin blood should
      provide a suitable nutrient medium for short-term (less than 4-hour) metabolic
      support of the endothelial surface and subjacent tissues.

PMID- 1372178
TI  - Concerted modulation by myelin basic protein and sulfatide of the activity of
      phospholipase A2 against phospholipid monolayers.
AB  - The effect of myelin basic protein (MBP) on the activity of phospholipase A2
      (PLA2, EC 3.1.1.4) against monolayers of dilauroylphosphatidylcholine (dlPC) or
      dilauroylphosphatidic acid (dlPA) containing different proportions of sulfatide
      (Sulf) and galactocerebroside (GalCer) was investigated. MBP was introduced into
      the interface by direct spreading as an initial constitutive component of the
      lipid-protein film or by adsorption and penetration from the subphase into the
      preformed lipid monolayers. The effect of MBP on PLA2 activity depends on the
      type of phospholipid and on the proportion of MBP at the interface. At a low mole
      fraction of MBP, homogeneously mixed lipid-protein monolayers are formed, and the
      PLA2 activity against dlPC is only slightly modified while the degradation of
      dlPA is markedly inhibited. This is probably due to favorable charge-charge
      interactions between dlPA and MBP that interfere with the enzyme action. The PLA2
      activity against either phospholipid is increased when the mole fraction of MBP
      exceeds the proportion at which immiscible surface domains are formed. GalCer has
      little effect on the modulation by MBP of the phospholipase activity. The effect
      of Sulf depends on its proportions in relation to MBP. The individual effects of
      both components balance each other, and a finely tuned modulation is regulated by
      the interactions of MBP with Sulf or with the phospholipid.

PMID- 1372179
TI  - Reconstitution of vacuolar ion channels into planar lipid bilayers.
AB  - Vacuolar ion channels were characterized after reconstitution into planar lipid
      bilayers. (1) Channel activity was observed after incorporation of tonoplast
      enriched microsomal membranes, purified tonoplast membranes or of solubilized
      tonoplast proteins. (2) Channels of varying single-channel conductances were
      detected after reconstitution. In symmetrical 100 mmol l-1 KCl, conductances
      between 1 and 110 pS were frequently measured; the largest number of independent
      reconstitution events was seen for single-channel conductances of 16-25 pS (28
      experiments), 30-42 pS (26), 49-56 pS (15) and 64-81 pS (15). Channel current
      usually increased linearly with voltage. (3) In asymmetrical solutions, cation-,
      non-selective and, for the first time for the tonoplast, anion-selective channels
      were detected. Ca(2+)-dependent regulation of channel opening was not observed in
      our reconstitution system. (4) Permeability was also observed for Cl-, NO3-,
      SO4(2-) and phosphate. (5) After fractionation of tonoplast proteins by size
      exclusion chromatography, ion channel activity was recovered in specific
      fractions. (6) Some of these fractions catalyzed sulfate transport after
      reconstitution into liposomes. The results suggest that different channels are
      active at the tonoplast membrane at a larger number than has been concluded from
      previous work.

PMID- 1372180
TI  - Effect of fatty acyl domain of phospholipids on the membrane-channel formation of
      Staphylococcus aureus alpha-toxin in liposome membrane.
AB  - By use of carboxyfluorescein-loaded multilamellar liposomes prepared from
      synthetic phosphatidylcholine (PC) or sphingomyelin and cholesterol in a molar
      ratio of 1:1, we studied whether or not fatty acyl domain of the phospholipids
      affects the membrane-damaging action (or channel formation) of Staphylococcus
      aureus alpha-toxin on the phospholipid-cholesterol membranes. Our data indicated:
      (1) that toxin-induced carboxyfluorescein-leakage from the liposomes composed of
      saturated fatty acyl residue-carrying PC and cholesterol was decreased with
      increasing chain length of the acyl residues between 12 and 18 carbon atoms,
      although toxin-binding to the liposomes was not significantly affected by the
      length of fatty acyl residue; (2) that unsaturated fatty acyl residue in PC or
      sphingomyelin molecule conferred higher sensitivity to alpha-toxin on the
      phospholipid-cholesterol liposomes, compared with saturated fatty acyl residues;
      and (3) that hexamerization of alpha-toxin, estimated by SDS-polyacrylamide gel
      electrophoresis, occurred more efficiently on the liposomes composed of PC with
      shorter fatty acyl chain or unsaturated fatty acyl chain. Thus, hydrophobic
      domain of the phospholipids influences membrane-channel formation of alpha-toxin
      in the phospholipid-cholesterol membrane, perhaps by modulating packing of
      phospholipid, cholesterol and the toxin in membrane.

PMID- 1372181
TI  - Thermal stability of hepatitis B surface antigen S proteins.
AB  - Thermal stability of hepatitis B surface antigen (HBsAg) has been studied by
      analyzing alterations in the native secondary structure and the antigenic
      activity. After heating for 19 h, circular dichrosim showed a cooperative
      transition with a midpoint at 49 degrees C. The conformational changes induced by
      temperature reduced the helical content of HBsAg S proteins from 49% at 23
      degrees C to 26% at 60 degrees C and abolished the antigenic activity, as
      measured by binding to polyclonal antibodies. Furthermore, the six different
      antigenic determinants recognized by our panel of monoclonal antibodies were also
      shown to be dependent on the native structure of HBsAg proteins. Hence, it can be
      inferred that these epitopes are conformation-dependent. Binding of monoclonal
      antibodies to HBsAg protected the native structure of the corresponding antigenic
      determinant from thermal denaturation. In fact, binding of one of the monoclonals
      tested resulted not only in protection of the corresponding epitope, but also in
      a consistent increase of antibody binding with increasing temperature. Such an
      increase in antibody binding occurred simultaneously with an increase in the
      fluidity of surface lipid regions, as monitored by fluorescence depolarization of
      1-(trimethylammoniophenyl)-6-phenyl-1,3,5-hexatriene. This correlation, along
      with the observation that lipids play an important role in maintaining the
      structure and antigenic activity of HBsAg (Gavilanes et al. (1990) Biochem. J.
      265, 857-864), allow to speculate the certain epitopes of HBsAg which are close
      to the lipid-protein interface, are dependent on the fluidity of the surface
      lipid regions. Thus, any change in the physical state of the lipids could confer
      a different degree of exposure to the antigenic determinants.

PMID- 1372182
TI  - Noise analysis and single-channel observations of 4 pS chloride channels in human
      airway epithelia.
AB  - Apical membranes of human airway epithelial cells have significant chloride
      permeability, which is reduced in cystic fibrosis (CF), causing abnormal
      electrochemistry and impaired mucociliary clearance. At least four types of
      chloride channels have been identified in these cells, but their relative roles
      in total permeability and CF are unclear. Noise analysis was used to measure the
      conductance of chloride channels in human nasal epithelial cells. The data
      indicate that channels with a mean conductance of 4.5 pS carry most of the
      chloride current, and that the mean number of such channels per cell is
      approximately 4,000. Chloride channels in this conductance range were also seen
      in single-channel recordings.

PMID- 1372183
TI  - Arguments in favor of an aggregational model of the gramicidin channel: a reply.

PMID- 1372184
TI  - Dimer versus tetramer.

PMID- 1372185
TI  - Defective glycosylphosphatidylinositol anchor synthesis in paroxysmal nocturnal
      hemoglobinuria granulocytes.
AB  - To investigate the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor
      in the granulocytes of paroxysmal nocturnal hemoglobinuria (PNH), the glycolipids
      of granulocytes from PNH patients and normal volunteers were biosynthetically
      labeled with [3H]mannose in the presence of tunicamycin. Extracted glycolipids
      were examined by thin-layer chromatography and compared with known biosynthetic
      intermediates. Normal granulocytes consistently showed [3H]mannose incorporation
      into the complete GPI core, several GPI biosynthetic intermediates, and dolichol
      phosphate mannose (DPM). The granulocytes of 10 patients with PNH that had no
      expression of CD55 and CD59 on greater than 95% of the cells were able to
      incorporate [3H]mannose into DPM, but were not able to incorporate detectable
      amounts into the complete GPI core. THus, PNH granulocytes do not synthesize
      detectable amounts of the complete GPI core and this defect likely accounts for
      the absence of GPI-linked membrane proteins on hematopoietic cells in this
      syndrome.

PMID- 1372186
TI  - Sustained human hematopoiesis in sheep transplanted in utero during early
      gestation with fractionated adult human bone marrow cells.
AB  - Sheep were transplanted in utero during early gestation with subpopulations of
      adult human bone marrow (BM) cells enriched for human progenitor and
      hematopoietic stem cells (HSC). Chimerism was documented in three of seven
      transplanted fetuses using monoclonal antibodies against human-specific
      hematopoietic cell lineages and/or cytogenetic analysis of BM and peripheral
      blood cells of recipients. Only chimeric sheep BM cells expressing CD45 (6.0% of
      total BM cells) formed human hematopoietic colonies in response to human
      recombinant cytokines as determined by cytogenetic analysis. Sorted CD45+ BM
      cells developed human T-cell colonies containing CD3+, CD4+, and CD8+ cells. DNA
      from chimeric BM cells obtained 3 months after birth displayed a finger printing
      pattern identical to that of DNA from the human donor of the HSC graft. These
      studies indicate that first trimester sheep fetuses are tolerant of adult human
      HSC grafts, thus permitting the creation of xenogeneic chimera expressing human
      myeloid and lymphoid lineages. The present findings also suggest that HSC grafts
      from immunologically competent, HLA-mismatched adult donors may be useful for
      correcting human genetic diseases in utero during early gestation.

PMID- 1372187
TI  - Cytokine regulation of colony-stimulating factor (CSF) production in cultured
      human synovial fibroblasts. II. Similarities and differences in the control of
      interleukin-1 induction of granulocyte-macrophage CSF and granulocyte-CSF
      production.
AB  - Synovial fibroblasts are likely to be a significant source of granulocyte
      macrophage colony-stimulating factor (GM-CSF) and granulocyte-CSF (G-CSF), which
      could be crucial to the pathogenesis of rheumatoid arthritis. Using specific
      enzyme-linked immunosorbent assays (ELISAs) and Northern analysis, GM-CSF and G
      CSF expression were followed in human synovial fibroblast-like cells in response
      to a number of agents, either alone or in the presence of an optimal stimulatory
      concentration of interleukin-1 (IL-1). For both CSFs, interferon-gamma (100 U/mL)
      did not increase their levels but dramatically suppressed the stimulatory action
      of IL-1, while basic fibroblast growth factor (10(-8) mol/L), although
      nonstimulatory by itself, potentiated IL-1 action. The glucocorticoid,
      dexamethasone (10(-7) mol/L), inhibited IL-1-stimulated CSF production. However,
      evidence was obtained for noncoordinated CSF regulation. Cyclooxygenase
      inhibitors potentiated the action of IL-1 on GM-CSF synthesis but suppressed G
      CSF synthesis, suggesting that endogenous cyclooxygenase products can have
      opposite effects in modulating the levels of each CSF. Also, the lymphokine, IL-4
      (250 pmol/L), slightly inhibited GM-CSF formation in the presence of IL-1 but
      elevated the G-CSF levels in these cultures without having an effect by itself.
      Transforming growth factor beta (less than or equal to 20 ng/mL) did not modulate
      levels of either CSF. Mesenchymal cell production of both GM-CSF and G-CSF is
      generally viewed as being under coordinate control; our findings suggest that
      their synthesis in IL-1-stimulated human synoviocytes can be modulated by a
      number of agents, in some cases with divergent actions depending on which CSF is
      examined.

PMID- 1372188
TI  - Effects of in vivo administration of interleukin-2 (IL-2) and IL-4, alone and in
      combination, on ex vivo human basophil histamine release.
AB  - Human basophils possess receptors for interleukin-2 (IL-2) and IL-4. The effect
      of 3 days of intravenous administration of IL-2 and/or IL-4 on basophil histamine
      release was examined in three groups of patients receiving IL-2, IL-4, or the
      combination of agents as part of a protocol to treat malignant melanoma or renal
      cell carcinoma. Because all patients received ranitidine for control of side
      effects, a control group of patients receiving ranitidine for Zollinger-Ellison's
      syndrome was also studied. IL-4 significantly inhibited IgE-mediated histamine
      release, while there was a trend for enhancement of IgE-mediated histamine
      release by IL-2. Administration of the combination of IL-2 and IL-4 did not alter
      IgE-mediated basophil histamine release. Both IL-2 and IL-4, alone and in
      combination, enhanced basophil histamine release induced by histamine releasing
      factors in human nasal washings. The effect of IL-2 alone was significantly
      greater than that of IL-4 alone or the combination of IL-2 plus IL-4. Taken
      together, the data suggest that when coadministered, IL-4 may inhibit the effects
      of IL-2 on basophils. Neither cytokine exerted any effect on basophil histamine
      release induced by the calcium ionophore A23187, nor did ranitidine cause any
      effects on histamine release induced by any of the stimulants. Thus, human
      basophil reactivity can be affected by IL-2 and by IL-4. The role that these two
      cytokines play in basophil function in vivo is likely to be complex.

PMID- 1372189
TI  - Internalization and intracellular fate of anti-CD5 monoclonal antibody and anti
      CD5 ricin A-chain immunotoxin in human leukemic T cells.
AB  - We have investigated the entry and subsequent intracellular fate of T101
      monoclonal antibody (MoAb) and T101-ricin A-chain (RTA) immunotoxin (IT) directed
      against the CD5 antigen (Ag) expressed on human leukemic CEM cells. We provide
      direct evidence for the internalization of T101 MoAb and the corresponding IT.
      Both the MoAb and IT were internalized at a relatively low rate. This slow
      internalization process could be related to the partial recycling of the MoAb/Ag
      or IT/Ag complexes. Analysis of the internalized molecules showed that their
      molecular weight was only partially altered after internalization and that no
      free A-chain could be found inside the cells, indicating that lysosomal
      degradation and cleavage of disulfide-linked conjugates is a quantitatively minor
      phenomenon compared with the localization of internalized anti-CD5 ITs in an
      endosomo-Golgi compartment, followed by their recycling to the cell surface. We
      believe that this is the major factor explaining the low efficacy of anti-CD5 IT
      when assayed in the absence of potentiating substances. Finally, we showed that
      the presence of ammonium chloride and monensin, which both dramatically enhance
      the kinetics of IT activity, did not affect the rate of internalization or the
      intracellular localization of the conjugate, suggesting that these activators
      could act at the postendocytotic level on a limited number of IT molecules.

PMID- 1372190
TI  - Isolation of the JMH antigen on a novel phosphatidylinositol-linked human
      membrane protein.
AB  - JMH is a high-frequency human erythrocyte blood group antigen. Previous work has
      shown that JMH is absent from complement-sensitive erythrocytes of patients with
      paroxysmal nocturnal hemoglobinuria (PNH); such cells have a broad defect in
      expression of phosphatidylinositol (PI)-linked proteins. Using both human JMH
      antisera and a JMH-like murine monoclonal antibody, we have identified a 76-Kd
      membrane protein present in JMH-positive but not JMH-negative erythrocytes. A
      similar 76-Kd JMH protein was also identified on a human lymphoid T-cell line,
      HSB-2. Using PI-specific phospholipase C, a small amount of JMH antigen could be
      cleaved from intact erythrocytes and immunoprecipitated from the supernate of
      treated erythrocytes, thus confirming that the protein bearing the JMH antigen is
      anchored by a PI-linkage to the erythrocyte membrane. This protein was further
      shown not to be identical to decay accelerating factor (70 Kd), a previously
      identified PI-anchored protein of somewhat similar molecular weight.

PMID- 1372191
TI  - The use of colony stimulating factors in combination.
AB  - More gene products that influence hematopoiesis continue to become available. As
      a result, is now possible to carry out both in vivo and in vitro studies with
      purified erythropoietin, various colony stimulating factors and 11 interleukins.
      The identification and availability of the ligand for the c-kit gene product has
      had a profound influence in the past year.

PMID- 1372192
TI  - Polymorphism of a long-chain cycloparaffin (CH2)120.
AB  - The polymorphism of a long-chain cycloparaffin (CH2)120 and chain packing in its
      crystals were discussed on the basis of some results obtained mainly by
      transmission electron microscopy. Monoclinic and orthorhombic single crystals of
      (CH2)120 were isothermally grown together from a dilute solution in p-xylene.
      Lozenge-shaped orthorhombic single crystals were more frequently observed than
      lath-shaped monoclinic ones. The basal surfaces of orthorhombic and monoclinic
      single crystal platelets were decorated with vapor-deposited polyethylene [PE].
      Orthorhombic single crystals of (CH2)120 with the (110) twin boundary and
      monoclinic ones with the (100) twin boundary were also observed. Rod-like edge-on
      crystals of (CH2)120 were grown from a dilute p-xylene solution onto the (001)
      surface of alkali halides. The crystal system of the (CH2)120 edge-on crystals
      depended on the kind of substrate. The monoclinic crystal was grown on NaCl, the
      orthorhombic one on KBr and KCl. The monoclinic form of (CH2)120 edge-on crystal
      was transformed to the orthorhombic one by annealing on NaCl. In both monoclinic
      and orthorhombic edge-on crystals, the molecular plane determined by two zigzag
      stems in a molecule of (CH2)120 was parallel to the substrate surface and the
      molecular axis (crystallographic c-axis) was perpendicular to the longer side of
      the rod-like edge-on crystals. The sub-cell dimensions of the stem chains in both
      forms of (CH2)120 crystals were very similar to those of monoclinic and
      orthorhombic PE crystals, respectively.

PMID- 1372193
TI  - Hepatitis C virus and organ donor cards.

PMID- 1372194
TI  - Extraosseous Ewing's sarcoma: report of a case and review of literature.
AB  - Extraosseous Ewing's sarcoma is a primitive small round cell neoplasm found in
      children and young adults. Extraosseous Ewing's sarcoma has been recognized as
      being histologically indistinguishable from Ewing's sarcoma of the bone and other
      round cell tumors. Our study reports the clinical course and histopathologic
      features of this rare variant, occurring in a 13 year-old boy, who presented with
      a subcutaneous tumor of the right thigh without osseous involvement. Wedge
      resection of the tumor was done followed by chemotherapy with Actinomycin-D,
      Oncovin and Endoxan.

PMID- 1372195
TI  - CD22 binds to alpha-2,6-sialyltransferase-dependent epitopes on COS cells.

PMID- 1372196
TI  - Free alpha-subunit, free beta-subunit of human chorionic gonadotropin (hCG), and
      intact hCG in sera of healthy individuals and testicular cancer patients.
AB  - To determine the serum concentrations of human chorionic gonadotropin (hCG), its
      free beta-subunit (hCG beta), and the free alpha-subunit (free alpha) common to
      all human glycoprotein hormones under physiological and pathological conditions,
      we developed monoclonal antibody-based immunoenzymometric assays. Free alpha
      subunit was detected in the sera of all healthy individuals of both sexes; hCG
      was measurable in sera of 54% of the men, and 46% were positive for free hCG
      beta; in nonpregnant women, 69.5% were positive for hCG, 68.4% for the free beta
      subunit. Pathological conditions, i.e., hCG-producing tumors, were studied in
      vitro and in vivo. In vitro, the concentrations of hCG, free hCG beta, and free
      alpha in tissue-culture supernates of a choriocarcinoma cell-line ("JAR") showed
      a parallel pattern during time-course analysis. In vivo, in long-term follow-up
      studies of 13 patients with testicular cancer, serum concentrations of the three
      analytes paralleled each other, whether the disease was in remission or not.
      Because of a selective increase of free hCG beta and free alpha in 27% of
      seminomatous tumor patients and in 13% of the nonseminomatous patients, the
      percentage of tumor-marker-positive sera was increased from 15% to 42% and 57% to
      70%, respectively, by the additional measurement of free hCG beta and free alpha.
      Thus hCG, free hCG beta, and free alpha are physiologically present in a high
      percentage of the sera from healthy men, and the determination of free hCG beta
      and free alpha, although not of prognostic value, improves the diagnostic
      possibilities in patients with testicular cancer.

PMID- 1372197
TI  - An autopsy case of late infantile and juvenile neuroaxonal dystrophy with diffuse
      Lewy bodies and neurofibrillary tangles.
AB  - The clinical and pathological features of a sporadic case of juvenile neuroaxonal
      dystrophy beginning at the age of 10 and leading to death at the age of 26 are
      described. Clinical manifestation began with cerebellar symptoms. The subject
      subsequently developed dementia, pes cavus (Friedreich's feet), epilepsy,
      myoclonus, and Parkinsonian syndrome, but demonstrated neither tremor nor
      choreoathetoid movement. Pathological examination showed typical generalized
      axonal dystrophy throughout the central nervous system (Seitelberger's disease).
      Iron-positive pigmentation was seen in the pallidonigral system, diffuse Lewy
      bodies (brainstem type and cerebral type) were demonstrated in the brainstem
      nuclei and cerebral cortex, and neurofibrillary tangles were observed.

PMID- 1372199
TI  - Bleomycin-induced lung injury in rats selectively abolishes hypoxic pulmonary
      vasoconstriction: evidence against a role for platelet-activating factor.
AB  - 1. The role of platelet-activating factor in the attenuated hypoxic pulmonary
      vasoconstriction associated with lung injury was evaluated using specific
      platelet-activating factor antagonists and an isolated perfused lung preparation.
      2. Intratracheal bleomycin was administered to rats to produce acute lung injury.
      Animals received intratracheal saline (control), intratracheal bleomycin or the
      platelet-activating factor antagonists BN 52021, WEB 2170 or WEB 2086 before and
      after bleomycin treatment. Forty-eight hours after intratracheal administration
      of bleomycin or saline the animals were killed. 3. The increases in pulmonary
      artery pressure during two periods of hypoxic ventilation and in response to 0.2
      microgram of angiotensin II were measured. Acetylcholine-induced vasodilatation
      after pre-constriction with prostaglandin F2 alpha was also measured. To quantify
      lung injury, the wet/dry ratio of lung weight was determined. 4. Bleomycin
      treatment attenuated the first and second hypoxic pressor responses by 93% and
      77%, respectively, but not the pressor response to angiotensin II nor the
      vasodilator response to acetylcholine. BN 52021 plus bleomycin augmented the
      first hypoxic pressor response compared with bleomycin treatment alone, but the
      structurally unrelated platelet-activating factor antagonists WEB 2170 and WEB
      2086 had no significant effect on the bleomycin-induced attenuation of hypoxic
      pulmonary vasoconstriction. None of the platelet-activating factor antagonists
      blocked the increase in the wet/dry lung weight ratio induced by bleomycin. 5.
      Bleomycin-induced lung injury selectively attenuates hypoxic pulmonary
      vasoconstriction, an effect that does not appear to be mediated by platelet
      activating factor. The mechanism remains to be elucidated, but may involve
      destruction of the hypoxic 'sensor' within the respiratory tract.

PMID- 1372198
TI  - Impact of CF summer camp.
AB  - In two consecutive years, patients with cystic fibrosis were studied at the
      beginning and end of a nine-day summer camp program to assess the program's
      effects on weight gain and pulmonary function. The camp experience includes daily
      exercise and a high-protein and high-fat diet. There were a total of 58 children
      between 6 and 12 years of age (42 different patients) and 10 adult counselors
      from 19 to 30 years of age (eight different patients). On the first and eighth
      days patients were weighed, sputum cultures were collected, and spirometry was
      performed. In year 2, peak expiratory flow rate was monitored daily. Also in year
      2, campers and counselors with CF were prescreened by sputum culture and excluded
      from camp if they had Pseudomonas cepacia in their sputum. Only one candidate
      screened was positive before camp. In year 1, no significant group changes in
      pulmonary function were identified. In year 2, significant increases on post-camp
      testing were found for FEF 25%-75% and PEF. Mean body weight for all patients
      increased significantly, by 0.4 kg in year 1 and 0.9 kg in year 2 (p less than
      .05). In year 1, a total of nine patients acquired a new organism in their follow
      up sputum culture, including five who acquired a new Pseudomonas species. There
      was no intra-cabin pattern of spread. Four patients were positive for P. cepacia
      on day 1 culture. No new subjects acquired this organism on follow-up
      examination. In year 2, only one subject had P. cepacia on the first camp
      collection; he alone was positive on day 9.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372200
TI  - Ferrous ions detected in cerebrospinal fluid by using bleomycin and DNA damage.
AB  - 1. During pathological states of iron-overload or oxidant stress, low-molecular
      mass iron can become available within extracellular fluids. 2. This iron would be
      converted to the ferrous state were it not for the protective anti-oxidant
      protein caeruloplasmin. 3. The ferrous-ion-oxidizing activity of caeruloplasmin
      rapidly converts ferrous ions back to the less reactive ferric state so that they
      can bind to available binding sites on transferrin. 4. Cerebrospinal fluids,
      however, often appear to contain low-molecular-mass iron, high levels of
      ascorbate and low levels of ferroxidase activity with little or no iron-binding
      capacity. 5. When iron ions are present in cerebrospinal fluid they are therefore
      likely to be in the ferrous state. 6. The development and application of an assay
      to speciate and measure ferrous ions in simple aqueous solution and their redox
      cycling activity in biological fluids is described.

PMID- 1372201
TI  - Systemic profiles of antigen-specific lymphocytes in animals chronically exposed
      to staphylococcus antigen in the mammary region.
AB  - Systemic profiles of lymphocytes were assessed in goats exposed chronically with
      Staphylococcus antigens in the supramammary region. Animals were inoculated three
      times subcutaneously in the right supramammary region with heat-killed
      Staphylococcus aureus antigen (HKS) at 1 month intervals. Prior to immunization
      and 1 week following each injection, 3 and 6 day cultures of peripheral blood
      mononuclear cells were made to determine proliferative responses of lymphocytes
      to HKS and the polyclonal T cell mitogen phytohemagglutinin (PHA). Peripheral
      blood lymphocytes responded significantly to both HKS and PHA in 3 day cultures
      after the second injection and showed peak responses after the final
      immunization, suggesting that repeated local injection of S. aureus antigen at
      the supramammary region, can induce an anamnestic response to the antigen in the
      peripheral blood of these animals with a concomitant increase in the
      responsiveness to the polyclonal mitogen, PHA. In contrast, initial antigen
      challenge induced little, if any, increase in responses to the specific antigen
      or mitogen when compared to pre-injection states. These data may also suggest
      that non-reactivity of peripheral blood lymphocytes to the HKS antigen
      immediately after the primary injection of antigen may be the result of local
      retention of antigen-reactive cells at the sites of infection.

PMID- 1372203
TI  - Improved staining method for the simultaneous flow cytofluorometric analysis of
      DNA content, S-phase fraction, and surface phenotype using single laser
      instrumentation.
AB  - We have developed an improved technique for triple staining that permits the
      simultaneous flow cytofluorometric analysis of cell surface antigens,
      bromodeoxyuridine incorporation into DNA, and DNA quantification using 7-amino
      actinomycin D. PHA-activated human peripheral blood lymphocytes were incubated
      with bromodeoxyuridine and stained for cell surface phenotype with phycoerythrin
      labeled monoclonal antibodies. Stained cells were fixed serially with 1%
      paraformaldehyde and 45% ethanol. Fixed cells were sequentially stained with an
      anti-BrdUrd monoclonal antibody followed by a FITC-conjugated goat anti-mouse
      antibody and incubated with 7-amino-actinomycin D. Hypotonic buffer was employed
      for all procedures after fixation. Stained-fixed cells were analyzed by flow
      cytofluorometry for simultaneous green (525 nm), orange (570 nm), and red
      (greater than 650 nm) fluorescence. Utilizing this staining technique, we were
      able to analyze simultaneously cell phenotype, DNA synthesis, and total cellular
      DNA content with single laser excitation.

PMID- 1372202
TI  - Fixation of mammalian cells for flow cytometric evaluation of DNA content and
      nuclear immunofluorescence.
AB  - Mammalian tissue culture cells were fixed with 3 different alcoholic fixatives-
      acetone:methanol, EtOH, and MeOH. The quality of the resulting DNA histograms was
      evaluated by comparison of CV, G1/G2 ratio, G1 mode, cell aggregation, and debris
      formation; 81-90% MeOH (final concentration) was determined to be the optimal
      fixative by these criteria. A procedure was then examined using a prefix with
      paraformaldehyde followed by MeOH (PF/MeOH). This procedure produced cell
      preparations with reduced debris and aggregation, equivalent mode and ratio, but
      increased CV when compared with MeOH fixation. Both MeOH and PF/MeOH fixation
      procedures were then compared for their utility in dual staining for DNA and
      intracellular immunofluorescence for a nuclear protein, SV40 T antigen (Tag).
      Since alcohols are known to affect immunofluorescence staining of some antigens,
      fixation with paraformaldehyde followed by Triton X-100 permeabilization (PF/TX)
      was also included in this comparison to generalize the study by providing an
      alternative to MeOH permeabilization. The three procedures were evaluated for the
      quality of the sample by measuring the same descriptors of the DNA parameter as
      in the alcohol study. PF/TX consistently produced samples with decreased DNA CV
      and less debris and aggregation compared to MeOH methods. Two criteria were used
      to evaluate immunofluorescence--the amount of Tag measured and reproducibility.
      All MeOH methods were equivalently reproducible with CV's less than 3%. PF/TX was
      slightly less so with a CV of less than 6%. In contrast, different levels of Tag
      were measured for each procedure. For mouse 3T3 cells infected with a recombinant
      retroviral vector encoding T antigen, the level of T antigen measured after
      PF/MeOH was 21% greater than in MeOH fixed cells, and the level in PF/TX fixed
      cells was 37% less. The fraction of fluorescence specific to T antigen for these
      cells was 79-83% for all procedures. The lower levels measured after fixation by
      PF/TX were shown to be due to epitope masking. Why higher levels are measured
      with PF/MeOH procedures is unknown at present but may be due to antigen
      retention. Therefore, each of these fixation methods may be used with confidence
      in reliability but they are not equivalent with respect to the molecular
      architecture of the nucleus. It is postulated that PF/TX permeabilizes cells but
      cells retain native supramolecular structure, whereas MeOH based fixatives
      disrupt this structure and randomize availability of epitope to antibody. If so,
      the two procedures could be used as complementary procedures to study gene
      expression and function.

PMID- 1372204
TI  - Flow cytometric analysis of whole blood lysis, three anticoagulants, and five
      cell preparations.
AB  - We studied the effects of anticoagulants and cell preparation methods on
      lymphocyte forward-angle scatter (FSC), autofluorescence, and immunofluorescent
      staining for CD45, CD14, and CD13. Blood samples collected in
      ethylenediaminetetracetic acid (EDTA), heparin, and acid citrate dextrose (ACD)
      were processed by using conventional Hypaque-Ficoll (HF) separation and four
      whole blood (WB) lysis techniques: Immuno-lyse, Q-Prep, FACS Lyse, and Gen Trak
      Lysis. Lymphocytes prepared by using three of the four whole blood methods gave
      FCS values comparable to those isolated by HF, while one method (FACS Lyse) gave
      consistently lower values. Autofluorescence values were comparable by all methods
      except Immuno-lyse, which showed consistently higher values in blood stored for
      24 h with any anticoagulant. Immunofluorescent values for CD45-stained cells were
      quite consistent across all methods, and among the whole blood methods, FACS Lyse
      and Q-Prep uniformly gave the highest purity of CD45-positive cells in the
      lymphocyte light scatter gates. Additionally, propidium iodide (PI) analyses of
      CD45-stained whole blood, and analyzed without lysis, confirmed that ACD and
      heparin were superior to EDTA for maintaining viable leucocytes overnight. Future
      studies should focus on other commonly used reagents, a wide variety of abnormal
      samples, and cell viability.

PMID- 1372205
TI  - Detection of granulocyte reactive oxygen species formation in whole blood using
      flow cytometry.
AB  - We have developed a technique for analysis of granulocyte reactive oxygen species
      formation in whole blood using flow cytometry and two color immunofluorescence.
      This technique relies upon the use of specific fluorescent dye (LDS-751) to stain
      nucleated cells, eliminating erythrocytes from analysis. Using LDS-751, forward
      angle light scatter, and 90 degrees side scatter, a granulocyte gate, monocyte
      gate, and lymphocyte gate were identified. Analysis with multiple FITC conjugated
      monoclonal antibodies demonstrated greater than 95% purity of a flow
      cytometrically identified granulocyte population in whole blood without physical
      manipulation of the blood. Utilizing 2'7' dichlorofluorescein diacetate (DCFH
      DA), we were able to measure granulocyte intracellular reactive oxygen species
      production. Dose response curves were obtained for the effect of granulocyte
      agonists phorbol myristate acetate, FMLP, and heat fixed Staphylococcus aureus on
      reactive oxygen species production. The techniques described in this paper should
      be useful for measuring granulocyte activation in vivo with flow cytometry.

PMID- 1372206
TI  - Multiparametric flow cytometric analysis of radiation-induced micronuclei in
      mammalian cell cultures.
AB  - A new flow cytometric method is presented that quantifies the frequency of
      radiation-induced micronuclei in mammalian cell cultures with high precision.
      After preparing a suspension of main nuclei and micronuclei stained with ethidium
      bromide and Hoechst 33258, both types of particles are measured simultaneously in
      a flow cytometer using forward light scatter and three fluorescence emission
      intensities excited by UV, 488 nm, and by energy transfer from Hoechst 33258 to
      ethidium bromide. Nonspecific debris overlapping the micronucleus distribution
      especially in the low fluorescence intensity region was discriminated from
      micronuclei by calculating ratios of the different fluorescences. The frequencies
      of radiation-induced micronuclei measured with this new technique agreed well
      with results obtained by conventional microscopy. The lower limit of the DNA
      content of micronuclei identified by this technique was found to be about 0.5%
      0.75% of the DNA content of G1-phase nuclei. Dose effect curves and the time
      dependent induction of micronuclei were measured for two different mouse cell
      lines.

PMID- 1372207
TI  - Expression of proliferation associated antigens in the cell cycle of synchronized
      mammalian cells.
AB  - Flow cytometric bivariate analysis was used to investigate the expression of
      PCNA, p120 and p145 during the cell cycle of a mammalian cell line (CHO-K1).
      Initially, aliquots of cells in exponential and plateau (G0) phase were analyzed
      for proliferation associated antigen expression. Expression of PCNA and p145
      during G0 was markedly depressed (less than 12% positive) while 54% of the G0
      cells stained positive for p120. The fluorescent intensity (mean channel
      fluorescence) of these G0 positive p120 cells, however, was only slightly above
      the mean channel fluorescence (MCF) of cells stained with a negative isotype
      control. In asynchronous cultures, all three antigens were expressed in greater
      than 70% of the cells, with PCNA staining being greater than 95%. Cells were then
      synchronized using mitotic selection (mitotic index of 97%) and antigen levels
      were measured as cells progressed synchronously through the cell cycle. From DNA
      analysis histograms, it appeared that the degree of synchrony was approximately
      90% throughout the remainder of the cell cycle. The bivariate DNA/PCNA, DNA/p120,
      and DNA/p145 histograms for mitotic cells indicated that both p120 and p145
      expression were elevated (percent positive and MCF) while PCNA levels were near
      controls (MCF). In early G1, all three markers were depressed (less than 12%
      positive); however PCNA levels rose precipitously in mid-G1 (greater than 50%
      positive). In late G1 to early S, p145 levels increased concomitantly with
      increases in p120. All three antigens were elevated throughout S phase and began
      to decline as cells moved from G2/M to G1 of the next cell cycle with p145
      expression decreasing first. This report indicates that all three proliferation
      associated antigens studied are differentially expressed in the cell cycle and
      therefore may be useful in detecting and assessing the proliferation state.

PMID- 1372208
TI  - Comparative evaluation of several DNA binding dyes in the detection of apoptosis
      associated chromatin degradation by flow cytometry.
AB  - Mouse thymocytes readily undergo apoptosis-associated DNA degradation upon
      exposure to glucocorticoids or ionizing radiation. It has been previously shown
      that flow cytometric cell cycle analysis of propidium iodide-stained apoptotic
      thymocytes results in the appearance of a distinct cell cycle region (the A0
      region) below the G0/G1 region. Cells in this region were shown to be undergoing
      apoptosis, and determination of apoptosis by flow cytometric analysis was
      proposed as a superior method for evaluating thymocyte apoptosis. In this study,
      a variety of DNA binding dyes with diverse primary binding mechanisms were
      evaluated for their ability to detect glucocorticoid and ionizing radiation
      induced apoptosis in mouse thymocytes. Apoptotic thymocytes stained with DNA
      binding dyes from the phenanthridinium, acridine, actinomycin, chromomycinone,
      anthracycline, and bisbenzimidazole groups all demonstrated clearly defined A0
      regions with percentages comparable to those obtained for propidium iodide. These
      results indicate that the appearance of the A0 region is not dependent on a
      particular dye binding characteristic and may be the consequence of extensive
      changes in chromatin structure resulting in a significant degree of dye
      exclusion.

PMID- 1372209
TI  - Flow cytometric DNA content of fresh tumor specimens using keratin-antibody as
      second stain for two-parameter analysis.
AB  - Studies concerning flow cytometric assessed DNA content reveal problems in
      interpretating DNA histograms of tumor specimens. The main problems are
      histograms with a broad coefficient of variation in the G0/G1 fraction; a high
      G2M fraction and samples with a low percentage of tumor cells. Therefore, in the
      present study, 382 fresh tumor specimens of carcinomas were analysed routinely,
      double labeled with, on the one hand, propidium-iodide for assessing DNA content
      and, on the other, a monoclonal keratin-antibody for marking epithelial and tumor
      cells. Of the 311 tumor samples, using single parameter analysis 165 (54%) were
      classified as DNA aneuploid and 146 (46%) as DNA "euploid." By double parameter
      analysis, 224 (72%) samples were keratin positive and 87 (27%) keratin negative
      and, of the 224 keratin positive tumors, 175 (78%) were DNA aneuploid and 49
      (22%) DNA euploid. The DNA histograms of single and double parameter analysis
      were compared and it was concluded that in 24 cases (11%) keratin labeling was
      necessary to recognize DNA aneuploidy. In another 23 (10%) cases, keratin
      labeling was helpful in assessing DNA aneuploidy. Finally when the results of the
      311 samples were combined, 215 (68%) were scored as DNA aneuploid and 99 (32%)
      DNA euploid. Thus the overall gain in assessing DNA aneuploidy using the double
      labeling technique is 14%. In conclusion, it is shown that keratin labeling on
      fresh tumor cell suspensions of epithelial tumors is of additional value in
      establishing DNA content. Because single parameter DNA assessment is adequate in
      approximately 60% of the tested samples, the double labeling technique can be
      performed routinely, or after initial single parameter DNA assessment. Histograms
      having a broad CV and/or a high G2M are good candidates for the double labeling
      technique. Using this technique, DNA-content assessment becomes more reliable.

PMID- 1372210
TI  - Flow cytometric two-color staining technique for simultaneous determination of
      human erythrocyte membrane antigen and intracellular malarial DNA.
AB  - A novel fixative and permeabilization method is described which allows
      simultaneous flow cytometric detection of red blood cell membrane antigen and
      intracellular malaria parasites. To illustrate the method, red blood cells from
      patients with paroxysmal nocturnal hemoglobinuria were infected with Plasmodium
      falciparum and maintained in synchronous red blood cell culture. The infected red
      blood cells were immunolabeled with antibodies directed to the complement
      regulatory protein decay-accelerating factor (DAF) followed by subsequent
      fixations in paraformaldehyde and then glutaraldehyde in phosphate-buffered
      saline. Finally, DNA of the intraerythrocytic parasites was stained with
      propidium iodide. Using this technique, cellular morphology was well preserved,
      no cell aggregation was observed, and high-quality indirect immunofluorescence
      and parasite DNA staining were obtained with negligible nonspecific labelling.
      Simultaneous measurement of parasite DNA and red blood cell membrane determinants
      makes possible the investigation of alterations of red cell membrane proteins in
      association with development of intracellular malaria parasites.

PMID- 1372211
TI  - Interferon may offer first drug therapy for diabetic retinopathy. New research
      showing that alpha-interferon blocks new blood vessel formation in the iris of
      monkeys may point the way to new treatment for diabetes retinopathy.

PMID- 1372212
TI  - [The rupture of a biliary metal endoprosthesis after electrocoagulation].

PMID- 1372213
TI  - Treatment of breast cancer in the 1990s. What does the future hold?

PMID- 1372214
TI  - Can pharmacological agents be used effectively in the alleviation of jet-lag?

PMID- 1372216
TI  - An overview of the role of calcium antagonists in the treatment of achalasia and
      diffuse oesophageal spasm.
AB  - Early studies confirmed the beneficial effects of calcium channel blockers on the
      normal oesophagus, which included a decrease in lower oesophageal sphincter tone
      in achalasia and a decrease in oesophageal contractions and amplitude in diffuse
      oesophageal spasm. This resulted in the enthusiastic use of the drugs in both
      disorders. With further experience, and with increased recognition of side
      effects, the role of these drugs in the 2 disorders has been better clarified.
      Clinical trials in general have not reflected the improvement observed in the
      manometric parameters. Only a minority of patients appear to derive sustained
      symptomatic benefit. Calcium channel blockers may be the initial choice for high
      or moderate risk patients with achalasia prior to proceeding with pneumatic
      dilatation or surgical myotomy. In diffuse oesophageal spasm, they are a
      reasonable first choice for all risk categories.

PMID- 1372215
TI  - Drug treatment of allergic conjunctivitis. A review of the evidence.
AB  - Allergic conjunctivitis, unlike several other ocular diseases, is seldom followed
      by permanent visual impairment; nevertheless, it is important because of both its
      frequency and its severity. Two major forms, seasonal and perennial, are
      considered in this review. To recognise the hallmarks of allergic conjunctivitis,
      clinicians have need of a thorough knowledge of its pathophysiological aspects
      and clinical features, enabling them to choose the best and most suitable therapy
      among the alternatives. The aims of treatment vary according to the symptoms,
      severity and characteristics of the allergic reactions; in general, treatment is
      based mainly on environmental control, pharmacotherapy and (sometimes) specific
      immunotherapy. Topical vasoconstrictors, decongestant compounds, standard
      antihistamines or combinations of these drugs have been used for a number of
      years to treat the acute and/or persistent symptomatology, and in order to
      prevent the side effects of a prolonged treatment with topical
      glucocorticosteroids. Nevertheless, the latter represent the most powerful anti
      inflammatory drugs, and are particularly recommended in short term treatment (5
      to 7 days) in severe acute symptomatology. Orally administered 'classic'
      antihistamines, i.e. histamine H1-receptor antagonists, are effective and very
      convenient in either short or long term treatment, largely because the new
      compounds also act on the inflammatory process secondary to the allergic events.
      Recently, other topical compounds such as sodium cromoglycate (cromolyn sodium),
      nedocromil and nonsteroidal anti-inflammatory drugs (NSAIDs) [i.e. piroxicam,
      aspirin] have become available. Sodium cromoglycate and nedocromil act as
      prophylactic compounds, able to prevent the allergic reaction; NSAIDs represent a
      valid and effective alternative to glucocorticosteroids in several situations.

PMID- 1372217
TI  - Wolff-Parkinson-White syndrome. Identification and management.
AB  - Patients with Wolff-Parkinson-White (WPW) pattern of ventricular pre-excitation
      may develop paroxysmal re-entrant tachyarrhythmias through the Kent bundle and,
      less commonly, atrial fibrillation. WPW patients are at risk of sudden death when
      a rapid ventricular response occurs during atrial fibrillation due to conduction
      through the accessory pathway. Conduction properties of the accessory pathway and
      atrial vulnerability, which is the propensity to develop atrial fibrillation, are
      important parameters for evaluation in these patients. The former can be assessed
      by means of noninvasive tests, such as stress and pharmacological tests, and with
      electrophysiological study; the latter only by electrophysiological study. There
      is no indication for treatment of asymptomatic patients. Antiarrhythmic
      prophylaxis is required in patients with previous episodes of atrial fibrillation
      with rapid ventricular response, in patients with paroxysmal re-entrant
      tachycardias and rapid conduction through the accessory pathway, and in patients
      with frequent episodes of re-entrant tachycardias of long duration. Vaughan
      Williams class IC anti-arrhythmic drugs (propafenone, flecainide) are the first
      choice for drugs in patients with rapid anterograde conduction through the
      accessory pathway due to their high efficacy and low incidence of adverse
      effects, while beta-blockers (atenolol, nadolol) are indicated for patients with
      re-entrant tachycardias and low conduction capacity through the bypass tract.
      When pharmacological therapy is ineffective, surgical or catheter ablation of the
      accessory pathway may be considered.

PMID- 1372218
TI  - Menorrhagia. Current drug treatment concepts.
AB  - Since menorrhagia occurs in 9 to 14% of populations of healthy women, many
      general practitioners will encounter menorrhagia-related problems. Menorrhagia is
      difficult to objectify and the choice of treatment between the available drugs is
      not always an easy one. In this survey, the available knowledge on menorrhagia
      diagnosis, underlying pathophysiology and treatment, especially medicinal
      treatment, are discussed. Overall, a practical approach is emphasised. The desire
      for contraception as well as the underlying cause of menorrhagia determine the
      drug of choice in the treatment of menorrhagia. If contraception is desired, oral
      combination contraceptives and continuously dosed progestogens, orally or as a
      medicated intrauterine device (IUD), are the first choice drugs for essential
      menorrhagia, and for fibroid- and bleeding disorder-associated menorrhagia. If no
      contraception is desired, the first choice treatments are drugs that need to be
      administered only during menstruation, such as prostaglandin synthesis inhibitors
      or antifibrinolytics. Of these, antifibrinolytics reduce menstrual blood loss to
      the greatest extent, whereas prostaglandin synthesis inhibitors have the lowest
      incidence of side effects. Prostaglandin synthesis inhibitors also have the extra
      advantage of diminishing dysmenorrhoea. There is no place for ergometrine in the
      treatment of menorrhagia. No studies are available as yet on the combination of
      various drug treatment modalities, although such an evaluation would be
      desirable.

PMID- 1372219
TI  - Current concepts in the pharmacological treatment of obsessive-compulsive
      disorder.
AB  - Obsessive-compulsive disorder (OCD) is a chronic and often disabling disease. OCD
      is characterised by intrusive, unwanted and persistently recurring mental events
      (obsessions) that usually evoke discomfort or anxiety, and/or repetitive
      ritualistic behaviours (compulsions) that are aimed at reducing discomfort and
      anxiety. However, the compulsions succeed only in achieving transient relief,
      followed by a growing sense of pressure. 10 years ago, OCD was considered a rare
      and treatment-refractory disorder. Recent well designed studies document a
      lifetime prevalence rate for OCD of more than 2% in the general population. The
      outlook for patients with OCD has changed in the last decade, with many well
      controlled studies showing that OCD patients respond to specific behavioural and
      pharmacological treatments. The specific form of behavioural therapy is in vivo
      exposure coupled with response prevention. Only serotonin reuptake inhibitors,
      such as clomipramine, fluoxetine and fluvoxamine, are effective in the treatment
      of both depressed and not depressed OCD patients. Fluoxetine and fluvoxamine lack
      the anticholinergic side effects of clomipramine and, thus, provide an
      alternative treatment for patients who cannot tolerate clomipramine. Other
      nonserotonergic antidepressants (tricyclics and monoamine oxidase inhibitors) and
      anxiolytic agents have not been found to be consistently effective in this
      disorder. Insufficient data on the efficacy of neuroleptics and their potentially
      irreversible side effects limit their use in OCD patients. Behavioural and the
      pharmacological treatment are complementary, and a combination of the 2 therapies
      is apparently more effective than either modality alone.

PMID- 1372220
TI  - Optimum management of the discharging ear.
AB  - Discharge from the ear can be the result of many disease processes. The ear may
      discharge blood, pus, cerebrospinal fluid (CSF) or wax. Keratosis obturans,
      stenosis of the external meatus and benign tumours of the external meatus all
      lead to wax build-up, which may cause recurrent attacks of otitis externa.
      Malignant tumours, such as basal cell carcinoma, squamous cell carcinoma and
      tumours of ceruminous gland origin may also present with discharge. Tumours
      should be excluded by submitting all material removed from the external canal for
      histological examination. Single or multiple abscesses (known as furuncles) may
      occur in the hair follicles in the skin of the external acoustic meatus (EAM).
      Compulsive scratching, hearing aids and foreign bodies placed in the ear
      predispose to otitis externa, which is also often associated with infection by
      Pseudomonas aeruginosa, Staphylococcus aureus and faecal organisms. Management
      may be with aluminium acetate 14%, topical antibiotic/steroid drops, a gauze wick
      soaked with icthammol 10% in glycerin or polymyxin B sulphate--neomycin sulphate-
      hydrocortisone acetate cream placed into the EAM and replaced every 24 to 48
      hours, or systemic antibiotics according to severity. Malignant (necrotising)
      otitis externa causes progressive destruction of the temporal bone, and cranial
      nerve palsies (usually facial first). Treatment is limited debridement of
      infected bone, accompanied by intravenous aminoglycosides, and local antibiotic
      treatment and aural cleanout or oral ciprofloxacin. Middle ear conditions causing
      discharge include acute otitis media, infected grommets, traumatic perforations
      and chronic suppurative otitis media, as well as tumours of the ear canal skin
      and middle ear, radiation-induced otitis externa and osteoradionecrosis of the
      temporal bone, tuberculosis, Langerhans cell histiocytosis, spontaneous or post
      traumatic CSF leaks, Wegeners granulomatosis and immune deficiency states.
      Topical application of aminoglycoside antibiotics to the middle ear of laboratory
      animals such as rats, guinea pigs and chinchillas causes sensorineural hearing
      loss, an effect rarely seen clinically in humans. If the external acoustic meatus
      and tympanic membrane are obscured by discharge cotton buds, microsuction
      equipment or syringing are used to remove it. It is often useful to initiate
      treatment (usually with topical drops, wicks or an oral antibiotic) with a
      provisional diagnosis. A full examination and adequate visualisation of the
      tympanic membrane must eventually be performed, if necessary under anaesthesia,
      or else serious progressive conditions may be neglected. The most useful initial
      investigation is a swab sent for bacteriological assessment; other investigations
      are usually indicated by clinical findings and the provisional diagnosis.

PMID- 1372223
TI  - Evoked potentials.

PMID- 1372221
TI  - Halofantrine. A review of its antimalarial activity, pharmacokinetic properties
      and therapeutic potential.
AB  - Halofantrine is an orally administered blood schizontocide which is active
      against both chloroquine-sensitive and chloroquine-resistant plasmodia. Dose
      finding and noncomparative clinical trials have confirmed the efficacy of
      halofantrine in the treatment of falciparum malaria in areas of chloroquine- and
      sulfonamide/pyrimethamine-resistant malaria and vivax malaria. However, poor
      results obtained in patients who failed mefloquine prophylaxis suggest that the
      efficacy of halofantrine may not extend to mefloquine-resistant P. falciparum,
      although more studies are needed to confirm this. Data concerning halofantrine in
      the treatment of P. ovale and P. malariae infections are still limited. One
      comparative study indicates that halofantrine has an efficacy equivalent to that
      of mefloquine and may be better tolerated. Halofantrine is generally well
      tolerated in both adults and children, the most common drug-associated effects
      being abdominal pain, pruritus, vomiting, diarrhoea, headache and rash, although
      it is difficult to distinguish between disease- and treatment-related events. The
      development of parasite resistance to halofantrine, like other blood
      schizontocides, is inevitable. Poor absorption resulting in variable peak plasma
      halofantrine concentrations, and possible cross-resistance with mefloquine, may
      accelerate the emergence of resistance to halofantrine. Thus, it is of primary
      importance that halofantrine is used only in areas where chloroquine- and
      sulfonamide/pyrimethamine-resistance are established in order to preserve and
      sustain its efficacy. If used with care, halofantrine will provide an important
      treatment option for falciparum malaria, a widespread parasitic disease
      associated with considerable morbidity against which the number of effective
      drugs available is being increasingly compromised by the spread of resistance.

PMID- 1372224
TI  - Steady-state visual evoked responses in high and low alpha subjects.
AB  - Reactivity to photic stimulation was studied in 16 subjects who were divided into
      2 groups based on the relative amounts of spontaneous EEG alpha produced during a
      4 min eyes-closed baseline condition. During the experimental session the
      subjects were presented with thirteen 1 min periods of sinusoidally modulated
      light stimulation at frequencies ranging from 2 Hz below their spontaneous peak
      alpha frequency (SPAF) to 2 Hz above in 0.33 Hz intervals. Using FFTs, steady
      state visual evoked responses (VERs) were extracted from each subject's EEG for
      each condition. VER magnitude for high alpha subjects varied with the proximity
      of the stimulus frequency to the SPAF, the VER for low alpha subjects did not.
      Conversely, low alpha subjects showed a similar effect in side-band alpha
      activity (once the VER had been extracted) whereas high alpha subjects did not.
      The results are explained in terms of a possible difference in the coupling
      strength between thalamic and cortical alpha sources.

PMID- 1372222
TI  - Terbinafine. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic potential in superficial mycoses.
AB  - Terbinafine is an orally and topically active allylamine antifungal agent with a
      primarily fungicidal action in vitro. Its spectrum of in vitro activity includes
      a broad range of dermatophyte, filamentous, dimorphic and dematiaceous fungi, and
      some yeast species. In clinical trials, mycological and overall efficacy rates of
      around 90 and 80%, respectively, have been achieved in cutaneous dermatophyte
      infections (tinea corporis/cruris and tinea pedis) with terbinafine, administered
      either orally (250 or 500 mg/day) or topically (a 1% cream applied twice daily).
      Similar rates of cure have been obtained with oral terbinafine in dermatophyte
      nail infections after relatively short treatment periods ranging from 3 to 12
      months. Topical terbinafine has been effective in approximately 80% of patients
      with cutaneous candidiasis or pityriasis versicolor. Few comparative data have
      been published, but generally oral terbinafine appeared to be at least as
      effective as oral griseofulvin or ketoconazole in tinea corporis/cruris and more
      effective than griseofulvin in tinea pedis. Both oral and topical terbinafine
      have been very well tolerated in clinical trials to date, with only minor adverse
      effects reported. Although further research is required to establish the efficacy
      of terbinafine in comparison with other available therapies, as well as to fully
      clarify its tolerability profile, the early results obtained with terbinafine in
      superficial fungal infections are very encouraging. Terbinafine appears likely to
      become a first-line therapy for dermatophyte infections, particularly those
      affecting the nails.

PMID- 1372225
TI  - Physiological functions of the ascending spinal tracts in HTLV-I-associated
      myelopathy (HAM).
AB  - Physiological functions of the spinothalamic tract (STT) and the posterior column
      (PC) were studied in 19 Japanese patients with HTLV-I-associated myelopathy
      (HAM). The former was evaluated by pain-related somatosensory evoked potentials
      (SEPs) following CO2 laser stimulation, and the latter by conventional SEPs
      following electrical stimulation. Conduction velocity of STT and PC was
      significantly decreased in 9 and 14 patients, respectively, and more than half of
      them showed no clinical impairment of sensations (subclinical abnormality).

PMID- 1372226
TI  - Human hand and lip sensorimotor cortex as studied on electrocorticography.
AB  - We investigated functional topography of human hand and lip sensorimotor cortex
      using somatosensory evoked potentials (SEPs) from chronically indwelling subdural
      grid electrodes (ECoG) in 3 epilepsy patients during stimulation of median nerve,
      ulnar nerve, and lower lip. We used dipole modeling to determine the cortical
      location of each peripheral sensory field. The cortical locations were in the
      postcentral gyrus and showed a clear somatotopic organization from medial
      superior to lateral inferior in the order: ulnar nerve, median nerve, and lip.
      The source localizations agreed with the results of cortical stimulations and
      anatomical features on intraoperative photographs. The cortical regions of median
      and ulnar nerve each could be modeled by sequential tangential and radial
      dipoles. The cortical region of lip was different and could be explained mostly
      by tangential dipoles. These findings suggest a difference in the cortical
      organization of human lip and hand sensory cortex and are consistent with a
      larger representation of lip in the posterior bank of central fissure in area 3b
      than on the gyral surface in area 1, similar to findings in macaque. Further
      studies in a larger population of patients with ECoG or normal subjects with
      scalp-EEG and MEG are warranted to test this hypothesis.

PMID- 1372227
TI  - Quantified EEG and cortical evoked responses in patients with chronic traumatic
      frontal lesions.
AB  - Eighteen frontal trauma patients and 17 age-matched control subjects had
      quantified EEGs and measurements of sensory (SEP) and auditory evoked potentials
      (P300) using a Biologic Brain Atlas III system. The findings were compared to the
      conventional paper EEG, and to the frontal lesion volumes, severity of head
      injury, and outcome variables. The quantified EEG confirmed the pathological
      findings detected by visual inspection, but some regional abnormalities were more
      easily detected by topographic mapping. The regional distribution of pathological
      slowing corresponded well with the morphological lesions in most patients. The
      modal frequency of EEG correlated both with lesion volume and injury severity and
      with the outcome variables. There were no pathological findings in the SEPs, and
      all but one patient had clearly distinguishable P300 responses. There was a
      significant reduction in P300 amplitude in the frontal patients at the anterior,
      but not at the posterior electrodes. The topographical distribution of the P300
      changes corresponded well with the morphological lesions. Our findings indicate
      that the P300 potential is, in part, dependent upon the prefrontal cortical
      areas. The present study thus supports P300 investigations which have shown
      amplitude reduction in other disorders (e.g., schizophrenia) with a presumed
      prefrontal dysfunction.

PMID- 1372228
TI  - Effects of temporal-parietal lesions on the somatosensory P3 to lower limb
      stimulation.
AB  - Temporal-parietal junction lesions reduce the auditory and upper limb
      somatosensory P3 event-related potential (ERP) to target and novel stimuli. The
      current study examined the somatosensory P3 to target and novel stimuli delivered
      to the sole of the foot in patients with unilateral temporal-parietal lesions (n
      = 6). Age-matched controls (n = 10) generated a parietal maximal target P3 and a
      frontal-central maximal novelty P3 ERP to foot stimulation. Unilateral temporal
      parietal lesions abolished target and novelty P3 responses over all scalp sites
      for stimuli delivered contralateral to the lesion. The P3 was also reduced to
      ipsilateral stimuli at electrodes over the lesioned hemisphere with partial P3
      preservation observed at electrode sites over the non-lesioned hemisphere. These
      results parallel the findings for upper limb stimulation and support the critical
      role of temporal-parietal cortex in P3 generation.

PMID- 1372229
TI  - AEPs at the onset and offset of repetitive sound modulation, due to mismatch with
      the contents of an auditory sensory store.
AB  - Long latency auditory evoked potentials (AEPs), chiefly consisting of a negative
      peak at about 150 msec and a positivity at 250 msec, were recorded at the
      beginning and end of periods during which the interaural time difference of
      binaural noise was switched between 0.0 and 0.8 msec at a fast rate (ISI = 50 or
      25 msec) or the frequency of continuous binaural clicks was switched between 167
      and 200 Hz every 80, 50 or 25 msec. In the latter case the offset responses
      occurred later than onset by a mean of 89, 47 and 27 msec respectively,
      suggesting they were probably generated at the moment the next switch was
      expected but failed to occur. The offset responses must be non-specific with
      respect to the interaural delay or the frequency of clicks, since neurones which
      respond to particular delays or frequencies and are made refractory by a rapid
      rate of stimulation should not suddenly become less so at the last in a series of
      identical stimuli, or be activated by the absence of a further event. It is
      proposed that the potentials are due to a higher order of neurone which
      automatically responds to the occurrence of a "mismatch" between the immediate
      sound and an image of that which was previously present, encoded in a short-term
      sensory store. In addition to frequency content and interaural delay, the image
      must contain information about the temporal modulation pattern of the sound over
      the previous few seconds.

PMID- 1372230
TI  - Effects of noise bandwidth on the late-potential masking level difference.
AB  - The masking level difference (MLD) is a psychoacoustic phenomenon derived from
      the subtraction of S pi No thresholds (signals pi radians out of phase and noise
      in phase at the two ears) from SoNo thresholds (signals and noise in phase at the
      two ears). The purpose of this study was to determine if the MLD derived from the
      late components (P1, N1, P2, N2) of the auditory evoked potentials was a
      physiological correlate of the behavioral MLD. Subjects were 15 young adults with
      normal hearing. Comparisons were made between behavioral and late potential
      thresholds to 500 Hz stimuli in So and S pi conditions in quiet, and to 500 Hz
      stimuli in SoNo and S pi No conditions in narrow band (50 Hz) and wide band (600
      Hz) noise. No significant differences were seen for behavioral or late-potential
      thresholds to So and S pi conditions. The S pi No thresholds was significantly
      lower than the SoNo threshold, yielding an MLD for both the behavioral and
      physiological responses. The magnitudes of both the behavioral and late-potential
      MLD were larger with the narrow band noise than with the wide band noise.
      Evidence, therefore, is provided that the late-potential MLD reflects similar
      processes as are responsible for the behavioral MLD.

PMID- 1372231
TI  - Midlatency auditory evoked responses: P1 abnormalities in adult autistic
      subjects.
AB  - MLR recordings from a group of 11 high-functioning adult autistic subjects were
      compared with those from a control group of 11 normal subjects. Components
      selected for analysis were "Pa", the maximum positivity in the 25-40 msec latency
      range following stimulus onset, "P1", the maximum positivity within the 50-65
      msec latency range, and "Nb," the maximum negative deflection in the 40-50 msec
      latency range. Statistical analyses of amplitude and latency data were conducted
      using repeated measures analysis of variance and t test group comparisons. The Pa
      component showed no significant difference between autistic and control groups.
      However, 2 types of abnormality were noted in the P1 component: (1) the P1
      component was significantly smaller in the autistic subjects at slow rates of
      stimulation, and (2) the autistic P1 did not change as rates of click stimulation
      increased from 0.5 to 10/sec, in contrast to the normally produced P1 decrement.
      Data from the P1 model in the cat, and complementary data from the human, closely
      link the generator substrate of the P1 potential to cholinergic components of the
      ascending reticular activating system (RAS) and their thalamic target cells. This
      is the first report of abnormal P1 responses in autism and strongly suggests that
      the RAS and/or its post-synaptic thalamic targets may be dysfunctional in this
      syndrome.

PMID- 1372232
TI  - Visual evoked potentials during spontaneously occurring spike-wave discharges in
      rats.
AB  - Flash evoked visual potentials (VEPs) were recorded in freely moving WAG/Rij
      rats. These rats show spontaneously occurring spike-wave discharges in the EEG,
      interpreted as absence-like seizures. VEPs recorded during the presence of spike
      wave discharges were compared with those obtained during normal states of
      vigilance as quiet wakefulness, slow-wave sleep and REM sleep. Almost similar
      VEPs were recorded during wakefulness and REM sleep, whereas during slow-wave
      sleep the second positive peak (P2) was considerably larger. In comparison with
      normal sleep-wake states, VEPs during spike-wave discharges showed unique
      changes, such as a decrease in the N1 amplitude, an increase of the P4 amplitude
      and an enhanced afterdischarge. Other characteristics were similar to those seen
      during slow-wave sleep, such as an increase of the P2 amplitude and a diminished
      P2-N3-P3 complex. These findings indicate sensory alterations during a spike-wave
      discharge. As expressed in the decrease of N1, afferent information cannot enter
      the thalamus during the rhythmic oscillatory mode. Such alterations may underlie
      the lowered responsiveness to external stimuli during spike-wave activity.

PMID- 1372233
TI  - A comparative analysis of enflurane anesthesia on primate motor and somatosensory
      evoked potentials.
AB  - The effect of increasing enflurane concentration on magnetic-induced myogenic
      cranial (Cr) and peripheral (Pr) motor evoked potentials (MEPs), and electrically
      induced median (MN) and posterior tibial (PTN) somatosensory evoked potentials
      (SEPs) was studied in 10 monkeys. MEP, recorded from abductor pollicis brevis and
      abductor hallucis muscles, and SEP (short- and long-latency scalp recorded
      potentials) variables were examined at 0.25, 0.5, 0.75, 1.0 MAC enflurane
      concentrations. Cr-MEPs progressively attenuated (P less than 0.01) with 0.25 MAC
      and were abolished (greater than or equal to 0.75 MAC) by graded enflurane
      concentration. Stimulation threshold for Cr-MEP was progressively elevated (P
      less than 0.01), and eventually reliable responses were lost (greater than or
      equal to 0.75 MAC). Marked scalp zone reduction to obtain Cr-MEP responses was
      noted with increasing enflurane concentration. Pr-MEPs and most SEP peaks
      maintained good replicability but showed significant amplitude reduction (P less
      than 0.01). MEP and SEP latency values were not significantly delayed as long as
      the wave form remained identifiable. We conclude that enflurane has a
      differential influence on Cr-MEPs and SEPs. Administration of enflurane should be
      discouraged while monitoring myogenic Cr-MEPs since even a subanesthetic
      concentration is profoundly detrimental.

PMID- 1372234
TI  - Stimulus rate-induced VEP attenuation in preterm infants.
AB  - The effect of the stimulus rate on the single flash VEP amplitude and latency
      (N1) was studied in 26 mechanically ventilated, preterm infants during the first
      days of life. Significant decreases in VEP amplitude and increases in latency
      were observed within a series of 3 single flash VEPs recorded with stimulus rates
      of 1/4 Hz. After a recovery period of 30 sec between series, the amplitude had
      attained baseline level, whereas the latency delayed progressively. The
      underlying cause of this rate effect is speculative, as individual degrees of VEP
      attenuation were not statistically related to gestational age, clinical state or
      cerebral oxygen delivery.

PMID- 1372235
TI  - Chemosensory event-related potentials in man: relation to olfactory and painful
      sensations elicited by nicotine.
AB  - The aim of this study was to investigate the topographical distribution of
      chemosensory event-related potentials in relation to stimulation with nicotine.
      The recognition thresholds of 3 different sensations elicited by nicotine (odor,
      burning, stinging) were determined. Subsequently, 3 concentrations of nicotine
      were applied which were just above mean threshold for each of the 3 sensations.
      Subjects rated the intensity of odor, burning, and stinging. Additionally, they
      tracked the time course of these sensations. Odor and stinging appeared
      immediately after stimulus onset. Burning started after several seconds.
      Intensity ratings of burning and stinging increased with rising stimulus
      concentrations, whereas the odorous sensation was strongest at medium
      concentrations. After low and medium stimuli largest mean amplitudes were
      parietally obtained, whereas following stimulation with the highest
      concentration, amplitudes peaked at Cz.

PMID- 1372236
TI  - Cellular generators of the cortical auditory evoked potential initial component.
AB  - Cellular generators of the initial cortical auditory evoked potential (AEP)
      component were determined by analyzing laminar profiles of click-evoked AEPs,
      current source density, and multiple unit activity (MUA) in primary auditory
      cortex of awake monkeys. The initial AEP component is a surface-negative wave,
      N8, that peaks at 8-9 msec and inverts in polarity below lamina 4. N8 is
      generated by a lamina 4 current sink and a deeper current source. Simultaneous
      MUA is present from lower lamina 3 to the subjacent white matter. Findings
      indicate that thalamocortical afferents are a generator of N8 and support a role
      for lamina 4 stellate cells. Relationships to the human AEP are discussed.

PMID- 1372237
TI  - Localization of insulin-like growth factor-binding protein-5 messenger
      ribonucleic acid in rat ovaries during the estrous cycle.
AB  - To investigate the potential role of insulin-like growth factor-binding protein-5
      (IGFBP-5) in ovarian physiology, we employed in situ hybridization and Northern
      analysis to localize IGFBP-5 mRNA in rat ovaries during the estrous cycle. By
      Northern analysis, the mRNA was abundant at all stages of the cycle. Two species
      of mRNAs were detected, with sizes of 6.0 and 1.8 kilobases, respectively. The
      relative amounts of the two transcripts changed throughout the cycle. By in situ
      hybridization, IGFBP-5 mRNA was expressed in only a few cell types: 1) granulosa
      cells of some atretic follicles, 2) some secondary interstitial cells, 3) some
      corpora lutea, and 4) the surface epithelium. The levels of message in both the
      granulosa and secondary interstitial cells changed over the cycle. At 1000 h on
      proestrus (before the LH/FSH surge), the message was expressed in only a few
      follicles. Interestingly, all were small atretic preantral (200-250 microns)
      follicles. At 2000 h on proestrus (after the LH/FSH surge), the IGFBP-5 mRNA was
      more abundant; now almost every atretic preantral follicle showed a strong
      hybridization signal. At 0200 and 1000 h on estrus, the mRNA appeared for the
      first time in granulosa cells of some atretic antral follicles and in secondary
      interstitial cells. Hence, virtually all atretic follicles, preantral and antral,
      now showed IGFBP-5 gene expression. In contrast to that on proestrus and estrus,
      the hybridization signal on diestrous days 1 and 2 was much less prominent and
      was found in only a few atretic preantral follicles. Throughout the cycle, IGFBP
      5 mRNA was evident in some corpora lutea, but it was not particularly prominent.
      Abundant IGFBP-5 mRNA was evident in the surface epithelium, and no change was
      detected over the cycle. Dominant follicles were devoid of IGFBP-5 mRNA. In
      conclusion, this paper presents the first evidence that the IGFBP-5 gene is
      expressed in the adult rat ovary. The IGFBP gene is expressed in a cell-specific
      manner, e.g. in atretic granulosa, secondary interstitial cells, corpora lutea,
      and the surface epithelium, and the stage of the cycle significantly affected
      message levels, especially in atretic granulosa and secondary interstitial cells
      around estrous morning. These findings suggest that IGBP-5 may be an
      autocrine/paracrine regulator of ovarian physiology, particularly in relation to
      preantral follicle atresia.

PMID- 1372238
TI  - Sensitive colorimetric bioassays for insulin-like growth factor (IGF) stimulation
      of cell proliferation and glucose consumption: use in studies of IGF analogs.
AB  - We have established two in vitro bioassay systems for quantification of insulin
      like growth factor (IGF) bioactivity. The first assay was used to quantitate
      mitogenic activity and the second was used to quantitate metabolic activity. Both
      assays use BALB/c 3T3 fibroblasts grown under serum-free conditions; detection of
      bioactivity in assays was performed colorimetrically and did not require the use
      of radioisotopes. The mitogenic bioassay, which requires 48 h for detection,
      quantitates changes in cell number and provides an index for determining the
      mitogenic activity of growth factors. Changes in cell number were measured by the
      enzymatic reduction of exogenously added MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5
      diphenyl-2H tetrazolium bromide] to MTT-formazan by mitochondrial enzymes, which
      was directly correlated to cell number. The metabolic bioassay, which requires 22
      h for detection, measures glucose consumption by detecting changes from the
      initial glucose concentration of conditioned medium after addition of various
      growth factors. When appropriate standards were established for these bioassays,
      they demonstrated a high level of reproducibility (coefficients of variation were
      0.085-0.096 for the mitogenic bioassay and 0.120-0.191 for the metabolic
      bioassay). Both assays can be performed in 96-well microtiter plates, without the
      use of radioisotopes, or the limitations of conventional glucose, amino acid, or
      thymidine incorporation studies. In initial experiments for assay specificity,
      epidermal growth factor had no measurable effect in either assay. However, IGF-I,
      IGF-II, and insulin demonstrated effects on both metabolism and mitogenesis. In
      the case of the mitogenic bioassay, the maximum mitogenic activation by these
      growth factors was approximately 180% of control, and these factors demonstrated
      parallel sigmoidal dose-response curves, ranging from 0.02-2 ng/ml for IGF-I and
      from 2-200 ng/ml for both IGF-II and insulin. In the metabolic bioassay, in
      contrast to the mitogenic bioassay, insulin showed a dose-response curve whose
      shape was different from those of IGF-I and IGF-II. IGF-I and IGF-II stimulated
      glucose consumption in dose-dependent ranges of 0.02-3 ng/ml and 0.4-40 ng/ml,
      respectively. However, the dose-response effect of insulin was wider, ranging
      from 0.1-2000 ng/ml. When these assays were used to measure the bioactivity of
      IGF analogs, a des(1-3)-IGF-I, which has decreased affinity for IGF binding
      proteins, demonstrated activity equivalent to IGF-I, a [Leu27]IGF-II, which has
      markedly diminished affinity for the type 1 IGF receptor, exhibited approximately
      0.07% of the potency of IGF-I and 1% of the potency of IGF-II.

PMID- 1372239
TI  - Interleukin-1 alpha and tumor necrosis factor-alpha differentially regulate
      enkephalin, vasoactive intestinal polypeptide, neurotensin, and substance P
      biosynthesis in chromaffin cells.
AB  - The pattern of expression of at least four neuropeptides contained in
      adrenomedullary chromaffin cells is altered by exposure to the cytokines
      interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF alpha),
      alone or in combination with stimulation of other second messenger pathways.
      Vasoactive intestinal polypeptide (VIP) was elevated 2- to 3-fold by 1 nM IL-1
      alpha within 48 h of exposure, while neurotensin and substance P synthesis were
      unaffected, and met-enkephalin levels were decreased 25-35%. Stimulation of VIP
      and substance P biosynthesis by forskolin was markedly enhanced by IL-1 alpha,
      while forskolin stimulation of enkephalin and neurotensin biosynthesis was
      unaffected. IL-1 alpha amplified the effect of phorbol myristate acetate to
      increase the VIP content of chromaffin cells, but antagonized phorbol ester
      induced elevation of neurotensin levels. TNF alpha also demonstrated a
      neuropeptide-specific pattern of modulation of second-messenger effects on
      chromaffin cell neuropeptide levels similar to those seen with IL-1 alpha. The
      neuroendocrine actions of IL-1 alpha described above, unlike IL-1 action in the
      immune system, do not appear to be mediated through IL-2 as this cytokine did not
      affect VIP or enkephalin expression in the presence or absence of protein kinase
      stimulation. Neither IL-1 alpha nor TNF alpha affected the calcium-coupled
      stimulation of neuropeptide secretion and biosynthesis that occurs in response to
      cell depolarization in these and other neuroendocrine cells in vitro and in vivo.
      These data provide a functional demonstration of IL-1 and TNF receptors in
      chromaffin cell cultures and suggest a physiological role for cytokine production
      in the adrenal medulla. Since both the magnitude and direction of neuropeptide
      synthesis modulation by IL-1 alpha and TNF alpha are highly peptide-specific, it
      appears that these cytokines do not merely augment second messenger pathways that
      affect neuropeptide synthesis, but potentially regulate the activity of factors
      controlling the pattern of neuropeptide gene expression in chromaffin cells.

PMID- 1372240
TI  - Role of Ca2+ on vasoactive intestinal peptide-induced glucose and adenosine 3',5'
      monophosphate production in the isolated perfused rat liver.
AB  - Livers from fed rats (180-240 g) were perfused noncyclically with a hemoglobin
      free medium in vitro to determine whether vasoactive intestinal peptide (VIP)
      increases hepatic glucose production through a cAMP- or a Ca(2+)-dependent
      mechanism. Glucose output did not increase, but cAMP increased maximally during
      10(-9) M VIP infusion. When VIP was perfused at 10(-8) M or more, glucose output
      increased dose dependently, whereas cAMP increased only a little during the VIP
      infusion, but increased greatly after the infusion. When Ca2+ was excluded from
      the perfusate, glucose output produced by 10(-8)-10(-7) M VIP was only 40% of
      that observed in the Ca(2+)-containing perfusion, and the increase in cAMP was
      abolished almost completely. By adding 10(-7) M A23187 for 10 min during the
      infusion of 10(-9) M VIP, cAMP, which increased with VIP alone, decreased during
      the A23187 infusion and increased again after the cessation of the A23187
      infusion, whereas glucose output increased during the A23187 infusion. These
      results were similar to those observed with higher concentrations of VIP. When
      10(-4) M isobutylmethylxanthine and 10(-8) M VIP were infused concurrently, cAMP
      increased rapidly during the infusion and decreased after the infusion. In
      conclusion, 1) glycogenolysis is produced by VIP through a Ca(2+)-dependent
      mechanism, rather than a cAMP-dependent one; and 2) the restriction of cAMP
      accumulation during the infusion of high concentrations of VIP is caused by
      Ca(2+)-induced phosphodiesterase activation.

PMID- 1372241
TI  - Immunocytochemical localization of estrogen and progestin receptors in the baboon
      (Papio anubis) uterus during implantation and pregnancy.
AB  - Although estrogen and progesterone are essential for the establishment of
      pregnancy in primates, localization of their specific receptors in uterine cell
      types during pregnancy has not been investigated. Therefore, uteri were obtained
      from baboons during the menstrual cycle, after steroid treatment, or during early
      pregnancy on days 18, 25 and 32 postovulation. Uterine and placental tissues were
      also collected from baboons during late pregnancy. Tissues were processed for
      indirect immunocytochemical localization with specific monoclonal antibodies
      against estrogen receptor (ER; H222) and progestin receptor (PR; JZB39).
      Identification of specific cell types was confirmed by iron-hematoxylin/van
      Gieson and Gimori's stains. Specific staining for steroid receptors was detected
      only in the nucleus. In the absence of ovarian steroid hormones (ovariectomized
      baboons), ER were present in glandular epithelium, stroma, and myometrial smooth
      muscle cells (SMC). In contrast, PR were absent from all uterine cell types. In
      the estrogen-dominated (follicular and estradiol treatment) uterus, ER and PR
      were detected in the nuclei of glandular and surface epithelium, stroma, and
      myometrial SMC. Elevated progesterone levels (luteal or after progesterone
      treatment) resulted in a loss of nuclear ER in stroma and epithelium, except in
      the deep glandular epithelium in the basalis. PR was maintained in the stroma
      throughout the endometrium, but was detected only in the epithelium of the deep
      glands. The myometrial SMC contained both ER and PR. In early pregnancy, ER was
      absent from the glands and stroma as early as day 18 postovulation, but was
      present in the wall of spiral arteries, blood vessels, and myometrial SMC. On day
      18 postovulation, staining for PR was absent from all glandular epithelium, but
      was maintained in the stroma surrounding the glands and spiral arteries, the wall
      of spiral arteries, blood vessels, and myometrial SMC. Stroma away from glandular
      epithelium contained few PR-positive cells. This staining pattern persisted
      throughout early pregnancy. No apparent differences in ER and PR localization
      were evident between the implantation and nonimplantation sites of the
      endometrium and myometrium. In late pregnancy, ER were only present in the SMC of
      the myometrium; however, PR were detected in stroma and myometrial SMC. The
      maternally derived decidua expressed PR, but not ER, in the majority of cells. In
      contrast, fetally derived tissues, placenta, and amnio-chorion, did not contain
      either ER or PR at any stage of pregnancy. Clearly, ER and PR persist in
      particular uterine cell compartments despite the continual high levels of
      progesterone in pregnancy and, thus, support a receptor-mediated mechanism for
      estrogen and progesterone regulation of implantation and pregnancy.

PMID- 1372242
TI  - Regulation of insulin-like growth factor-binding proteins in the baboon (Papio
      anubis) uterus during early pregnancy.
AB  - The baboon uterus begins to synthesize insulin-like growth factor-binding protein
      1 (IGFBP-1) in the deep glands of the late secretory endometrium, and this
      protein then becomes the major secretory product of the term decidua. We
      hypothesized that the placenta and/or conceptus may regulate the synthesis and
      secretion of IGFBP-1 by decidualized stromal cells during pregnancy. To test this
      hypothesis, tissue was obtained from pregnant baboons on days 18, 25, and 32
      postovulation. The uterus was separated into three regions: RI (directly below
      the implantation site), RII (adjacent to the implantation site), and RIII
      (opposite the implantation site). Portions of the tissue were fixed in Bouin's
      solution for immunocytochemistry, and the remainder was subdivided into
      functionalis, basalis, and myometrium and subjected to organ explant culture. The
      placenta was fixed or cultured separately. Ligand blot analysis of functionalis
      medium showed that the major IGFBP had a mol wt (Mr) of 29,000-31,000; however, a
      doublet of 37,000-43,000 Mr and a band at 24,000 Mr were also present. The
      functionalis from all regions expressed the majority of the IGFBPs, but basalis
      from RI tissue also secreted the same array of IGFBPs on days 25 and 32. Ligand
      blot analysis of placental medium proteins revealed a doublet at Mr 37,000-43,000
      on days 25 and 32, but not on day 18. Immunoprecipitation followed by ligand blot
      analysis of medium proteins using polyclonal antibodies to IGFBP-1 and IGFBP-2
      and -3 confirmed that IGFBP-1 and -2 were the predominant products of the
      endometrium and decidua, while IGFBP-3 was synthesized by the placenta.
      Immunocytochemistry with a monoclonal antibody to IGFBP-1 demonstrated intense
      glandular epithelial staining in all regions on days 18, 25, and 32. Stromal
      staining for IGFBP-1 was first evident on day 25 and was only present in stromal
      cells in intimate contact with the trophoblastic tissue. By day 32, IGFBP-1
      expression was not limited to the endometrial-trophoblastic junction, but
      extended to the deeper stromal cells and included the perivascular regions. IGFBP
      1 staining was most intense in RI, but stromal cells at the luminal surface and
      those surrounding the spiral arteries also showed some staining in RII and RIII
      on day 32. These studies suggest that the baboon placenta and/or conceptus
      regulate IGFBP expression in the uterine endometrium during the initial stages of
      pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1372243
TI  - The effect of androgen, estrogen, and growth factors on the proliferation of
      cultured fibroblasts derived from human fetal and adult prostates.
AB  - Stromal enlargement plays a key role in the development of benign prostatic
      hypertrophy in humans. Human prostatic fibroblasts were obtained from fetal and
      adult prostates and characterized as to their androgen and estrogen receptor
      status and growth in response to dihydrotestosterone (DHT), estradiol (E2),
      hydroxyflutamide (OH-FLU), hydrocortisone, basic fibroblast growth factor (bFGF),
      and epidermal growth factor (EGF). In addition, the ability of hormones and
      growth factors to induce the messenger RNA (mRNA) for the c-fos protooncogene was
      assessed as a measure of the early, direct effects of these compounds on cellular
      proliferation. Nuclear androgen receptors were demonstrable by
      immunocytochemistry in both fetal and adult cells. Nuclear estrogen receptor
      staining was negative. Neither E2 nor hydrocortisone increased cellular
      proliferation. Both EGF and bFGF did increase cellular growth. DHT (10(-8)-10(-7)
      M) had a significant stimulatory effect on cell growth only in serum-free media.
      OH-FLU addition enhanced DHT induced proliferation. Changing the media during the
      course of the experiment obliterated the stimulatory effect of DHT. Both EGF (10
      ng/ml) and bFGF (20 ng/ml) increased the mRNA for the c-fos protooncogene. DHT
      (10(-7) M) did not induce the mRNA for c-fos. We conclude that EGF, bFGF, and DHT
      (especially in combination with OH-FLU) increase the proliferation of human
      prostatic fetal and adult fibroblasts in vitro. E2 has no effect on fibroblast
      proliferation. The stimulatory effects of EGF and bFGF are direct, whereas the
      effect of DHT appears to be indirect, possibly mediated via the increased
      production and/or secretion of growth factors.

PMID- 1372244
TI  - Identification of a conserved region required for hormone dependent
      transcriptional activation by steroid hormone receptors.
AB  - The oestrogen receptor stimulates transcription by means of at least two distinct
      transcriptional activation domains, TAF-1 in the N-terminal domain and TAF-2 in
      the hormone binding domain. Here we show that TAF-2 activity requires a region in
      the C-terminus of the hormone binding domain between residues 538 and 552 in the
      mouse oestrogen receptor which is conserved among many nuclear hormone receptors.
      Point mutagenesis of conserved hydrophobic and charged residues significantly
      reduced ligand dependent transcriptional activation but had no effect on steroid
      or DNA binding. Mutation of the corresponding residues in the glucocorticoid
      receptor also abolished transcriptional activation. We therefore propose that the
      conserved region may be essential for ligand dependent transcriptional activation
      by other members of the nuclear receptor family.

PMID- 1372246
TI  - A conserved 11 nucleotide sequence contains an essential promoter element of the
      maize mitochondrial atp1 gene.
AB  - To determine the structure of a functional plant mitochondrial promoter, we have
      partially purified an RNA polymerase activity that correctly initiates
      transcription at the maize mitochondrial atp1 promoter in vitro. Using a series
      of 5' deletion constructs, we found that essential sequences are located within-
      19 nucleotides (nt) of the transcription initiation site. The region surrounding
      the initiation site includes conserved sequence motifs previously proposed to be
      maize mitochondrial promoter elements. Deletion of a conserved 11 nt sequence
      showed that it is critical for promoter function, but deletion or alteration of
      conserved upstream G(A/T)3-4 repeats had no effect. When the atp1 11 nt sequence
      was inserted into different plasmids lacking mitochondrial promoter activity,
      transcription was only observed for one of these constructs. We infer from these
      data that the functional promoter extends beyond this motif, most likely in the
      5' direction. The maize mitochondrial cox3 and atp6 promoters also direct
      transcription initiation in this in vitro system, suggesting that it may be
      widely applicable for studies of mitochondrial transcription in this species.

PMID- 1372245
TI  - Alternatively spliced transcripts of the Drosophila tramtrack gene encode zinc
      finger proteins with distinct DNA binding specificities.
AB  - A protein present in nuclear extracts of Drosophila embryos binds multiple sites
      in the promoter and genetically defined autoregulatory element of the pair-rule
      gene even-skipped (eve). We reported here the isolation of a cDNA encoding this
      binding activity, the sequence of which identifies it as the 69 kDa zinc finger
      tramtrack (ttk) protein. As ttk was previously implicated in controlling the
      expression of another pair-rule gene, fushi tarazu (ftz), our findings suggest
      that ttk plays a role in the regulation of at least two developmentally important
      genes. An additional ttk-related cDNA clone was isolated which gives rise to an
      88 kDa protein with an alternative set of zinc fingers having a DNA binding
      specificity distinct from that of the 69 kDa protein. Both proteins were shown to
      be encoded by the ttk gene through alternative splicing, providing the first
      example of the use of this mechanism to generate related proteins with distinct
      DNA binding specificities. Whole mount in situ hybridization analysis revealed
      different patterns of embryonic expression of the two ttk mRNA isoforms.

PMID- 1372247
TI  - Distinct modes of transcription read through or terminate at the c-myc
      attenuator.
AB  - Premature termination of transcription by RNA polymerase II (pol II) occurs in
      the 5' region of many viral and cellular genes. Modulation of this process, or
      attenuation, is an important means of transcriptional control, but its mechanism
      is unknown. Using injected Xenopus oocytes, the efficiency of the mouse c-myc
      attenuator was tested when it was placed at various distances from the
      transcription initiation site. The attenuator functioned with each of six
      different pol II promoters tested; however, termination efficiency declined
      markedly when it was placed more than approximately 400 bases from the start
      site. This decline in attenuator function with distance from the start site
      coincided with increased sensitivity to the pol II inhibitor 5,6-dichloro-1-beta
      D-ribofuranosyl benzimidazole (DRB). Thus transcription complexes situated
      further from the promoter appear to have a lower ability to recognize the
      attenuator and a greater sensitivity to DRB. Furthermore, polymerases which have
      read through one attenuation site have a reduced ability to terminate at a second
      site. The results imply that a discrete subset of elongation complexes is capable
      of premature termination, and that this subset exists only within the first few
      hundred bases of the transcription unit. Regulation of termination efficiency may
      be effected by changing the balance between the two modes of transcription
      committed either to read through or to terminate prematurely.

PMID- 1372248
TI  - Domain structure of the human immunodeficiency virus reverse transcriptase.
AB  - The spatial arrangement of subunits p51 and p66 of the HIV-1 reverse
      transcriptase and the position of the RNase H containing domain, p15, have been
      determined by means of neutron small-angle scattering. The reverse transcriptase
      (p66/p51) is a flat molecule, which can be approximated by an ellipsoid with the
      half axes of 5.2 nm, 4.8 nm and 1.4 nm. The two subunits p51 and p66 having a
      centre-to-centre distance of 3.3 +/- 0.3 nm are attached at their flat sides,
      slightly shifted sideways. The p15 domain is located at the long axis of the
      ellipsoidal reverse transcriptase having a distance of 5.0 +/- 0.5 nm to the
      centre of the p51d domain, which is part of the p66 subunit, and a distance of
      5.3 +/- 1.2 nm to the centre of the neighbouring p51s subunit.

PMID- 1372249
TI  - Replication control in plasmid R1: duplex formation between the antisense RNA,
      CopA, and its target, CopT, is not required for inhibition of RepA synthesis.
AB  - The replication frequency of plasmid R1 is regulated by an antisense RNA, CopA,
      which inhibits the synthesis of the rate-limiting initiator protein RepA. The
      inhibition requires an interaction between the antisense RNA and its target,
      CopT, in the leader of the RepA mRNA. This binding reaction has previously been
      studied in vitro, and the formation of a complete RNA duplex between the two RNAs
      has been demonstrated in vitro and in vivo. Here we investigate whether complete
      duplex formation is required for CopA-mediated inhibition in vivo. A mutated copA
      gene was constructed, encoding a truncated CopA which is impaired in its ability
      to form a complete CopA/CopT duplex, but which forms a primary binding
      intermediate (the 'kissing complex'). The mutated CopA species (S-CopA) mediated
      incompatibility against wild-type R1 plasmids and inhibited RepA-LacZ fusion
      protein synthesis. Northern blot, primer extension and S1 analyses indicated that
      S-CopA did not form a complete duplex with CopT in vivo since bands corresponding
      to RNase III cleavage products were missing. An in vitro analysis supported the
      same conclusion. These data suggest that formation of the 'kissing complex'
      suffices to inhibit RepA synthesis, and that complete CopA/CopT duplex formation
      is not required. The implications of these findings are discussed.

PMID- 1372250
TI  - An archaebacterial terminal oxidase combines core structures of two mitochondrial
      respiratory complexes.
AB  - The operon coding for a respiratory quinol oxidase was cloned from
      thermoacidophilic archaebacterium Sulfolobus acidocaldarius. It contains three
      genes, soxA, soxB and soxC. The first two genes code for proteins related to the
      cytochrome c oxidase subunits II and I, respectively. soxC encodes a protein
      homologous to cytochrome b, which is a subunit of the mitochondrial and bacterial
      cytochrome c reductases and the chloroplast cytochrome b6f complex. soxA is
      preceded by a promoter and the genes are cotranscribed into a 4 kb mRNA. Their
      protein products form a complex which has been partially purified and has quinol
      oxidase activity. The reduced minus oxidized absorption spectrum of the complex
      has two maxima at 586 and 606 nm. The latter is typical of cytochrome c oxidase.
      The complex contains four haems A. Two haems belong to the 'cytochrome oxidase'
      part of the complex and two are probably bound to be apocytochrome b (SoxC) and
      responsible for the 586 nm absorption peak. The homology between the sox gene
      products and their mitochondrial counterparts suggests that energy conservation
      coupled to the quinol oxidation catalysed either by the Sulfolobus oxidase or two
      mitochondrial respiratory enzymes may have a similar mechanism.

PMID- 1372252
TI  - Translocation of pp60c-src to the cytoskeleton during platelet aggregation.
AB  - The high amount of pp60c-src in platelets has led to speculation that this kinase
      is responsible for tyrosine-specific phosphorylation of cellular proteins during
      platelet activation by different agonists, and is, therefore, implicated in
      signal transduction of these cells. Unlike pp60v-src, the association of which
      with the cytoskeleton appears to be a prerequisite for transformation, pp60c-src
      is detergent-soluble in fibroblasts overexpressing the c-src gene, and its role
      in normal cellular function remains elusive. To gain a better understanding of
      the function of pp60c-src we have investigated the subcellular distribution of
      pp60c-src and its relationship to the cytoskeleton during platelet activation.
      Quantitative immunoblotting and immunoprecipitation have revealed that pp60c-src
      is detergent-soluble in resting platelets, while 40% of total platelet pp60c-src
      becomes associated with the cytoskeletal fraction upon platelet activation. We
      have also shown that a small pool of pp60c-src is associated with the membrane
      skeletal fraction which remains unchanged during the activation process. The
      interaction of pp60c-src with cytoskeletal proteins strongly correlates with
      aggregation and is mediated by GPIIb/IIIa receptor-fibrinogen binding. We suggest
      that the translocation of pp60c-src to the cytoskeleton and its association with
      cytoskeletal proteins may regulate tyrosine phosphorylation in platelets.

PMID- 1372251
TI  - Isolation of a hagfish gene that encodes a complement component.
AB  - It has been widely accepted that cyclostomes are the most primitive vertebrates
      extant with the ability to produce antibodies. We isolated cDNA clones that
      encode a putative 'antibody' from one of the cyclostomes, Eptatretus burgeri. The
      amino acid sequence predicted from the nucleotide sequences of the cDNA clones
      indicated that this gene does actually encode the proteins isolated as hagfish
      'antibodies' by various investigators. However, these proteins are not similar to
      mammalian immunoglobulins but have some characteristics common to complements C3,
      C4 and C5 in higher vertebrates. We discuss the relationships of the isolated
      gene for hagfish complement with the mammalian genes for complements C3, C4 and
      C5. We also discuss the possibility of the presence of antibodies in cyclostomes.

PMID- 1372253
TI  - Transfection of wild-type CFTR into cystic fibrosis lymphocytes restores chloride
      conductance at G1 of the cell cycle.
AB  - We complemented the Cl- conductance defect in cystic fibrosis lymphocytes by
      transfection with wild-type cDNA for the cystic fibrosis transmembrane
      conductance regulator (CFTR). Stable transfectants were selected and subjected to
      molecular and functional analyses. We detected expression of endogenous CFTR mRNA
      in several CF and non-CF lymphoid cell lines by PCR. Expression from cDNA in the
      transfectants was demonstrated by amplifying vector-specific sequences. Both
      fluorescence and patch-clamp assays showed that transfectants expressing wild
      type CFTR acquired properties previously associated with Cl- conductance (GCl)
      regulation in non-CF lymphocytes: (i) GCl was elevated in the G1 phase of the
      cell cycle, (ii) cells fixed at G1 increase GCl in response to increased cellular
      cAMP or Ca2+, (iii) agonist-induced increases in GCl were lost as the cells
      progressed to the S phase of the cell cycle. The cell cycle and agonist dependent
      regulation of GCl was not observed in CF lymphocytes transfected with CFTR cDNA
      containing stop codons in all reading frames at exon 6. Our findings indicate
      that lymphocytes express functional CFTR since wild-type CFTR corrects the
      defects in Cl- conductance regulation found in CF lymphocytes. Evaluation of the
      mechanism of this novel, CFTR-mediated regulation of GCl during cell cycling
      should provide further insights into the function of CFTR.

PMID- 1372254
TI  - Calcium influx through subunits GluR1/GluR3 of kainate/AMPA receptor channels is
      regulated by cAMP dependent protein kinase.
AB  - Excitatory synaptic transmission in the central nervous system (CNS) is mediated
      by three major classes of glutamate receptors, namely the ionotropic NMDA (N
      Methyl-D-Aspartate) and KA/AMPA (kainate/alpha-amino-3-hydroxyl-5-methylisoxazole
      4-propionic acid) receptors and the metabotropic receptor type. Among the
      ionotropic receptors, NMDA receptors are thought to mediate their physiological
      response mainly through the influx of extracellular calcium, while KA/AMPA
      receptor channels are mainly thought to carry the influx of monovalent cations.
      Recently, we have challenged this view by showing that cloned KA/AMPA receptor
      subunits GluR1 and GluR3 form ion channels which are permeable to calcium. We now
      directly demonstrate large increases in intracellular calcium concentrations
      induced by calcium fluxes through KA/AMPA receptor channels in solutions with
      physiological calcium concentrations. Calcium fluxes were observed through
      glutamate receptor channels composed of the subunits GluR1 and GluR3, which are
      both abundantly present in various types of central neurones. The calcium influx
      was fluorometrically monitored in Xenopus oocytes injected with the calcium
      indicator dye fura-2. Bath application of the membrane permeable analogue of
      adenosine cyclic monophosphate (cAMP) potentiated the current and also the flux
      of calcium through open KA/AMPA receptor channels. Further pharmacological
      experiments suggested that this effect was mediated by the activation of protein
      kinase A. Our results provide a molecular interpretation for the function of
      calcium permeable KA/AMPA receptor channels in neurones and identify two of the
      subunits of the KA/AMPA receptor channel which are regulated by the cAMP
      dependent second messenger system.

PMID- 1372256
TI  - Gene transfer experiments imply instructive role of major histocompatibility
      complex class I molecules in cellular peptide processing.
AB  - DBA/2-derived mouse tumor cells were transfected with the H-2 Kb gene. Naturally
      processed minor histocompatibility (H) peptides were extracted from both
      transfected and non-transfected cells by acid elution, and were separated by high
      performance liquid chromatography. Kb-restricted minor H epitopes corresponding
      to H-4b and mapki, both encoded by non-major histocompatibility complex genes of
      DBA/2, were readily detected by the respective cytotoxic T lymphocyte in peptides
      extracted from Kb-transfected, but not from non-transfected or Db-transfected
      cells. Titration experiments indicated at least 3000-fold less copies of
      correctly processed Kb-restricted epitopes in cells without Kb as compared to
      cells with Kb. Since we estimate the copy number of Kb-restricted H-4b epitopes
      in Kb-expressing transfectants to be less than 1000 per cell, the pool size of H
      4b epitopes correctly processed in the absence of Kb should be less than 1/3 copy
      per cell.

PMID- 1372255
TI  - Modulation of homeobox gene expression alters the phenotype of human
      hematopoietic cell lines.
AB  - We have previously reported that certain genes of the HOX2 cluster of homeobox
      genes on human chromosome 17 are specifically expressed in human leukemic cell
      lines with erythroid potential, suggesting that these genes are involved in
      hematopoietic differentiation. We now show that the expression of the HOX 2.2
      gene decreases during erythropoietin-induced differentiation of the erythroid
      cell line MB02. In order to study the role of the HOX 2.2 homeobox gene in
      hematopoiesis, vectors producing sense or antisense transcripts were introduced
      into K562 and HEL cells, pluripotent lines with erythroid and myeloid features.
      Overexpression of HOX 2.2 is associated with loss of erythroid features in both
      lines and an increase in certain myelomonocytic markers in K562 cells. Expression
      of antisense HOX 2.2 is associated with an increase in erythroid features in HEL
      cells and a mild decrease in myeloid characteristics in K562 cells.
      Overexpression of the adjacent HOX 2.1 gene in K562 cells does not produce
      similar phenotype changes. These data demonstrate that modulation of a specific
      HOX 2 homeobox gene can change the phenotype of somatic cells and suggest that
      certain HOX 2 genes play a role in blood cell differentiation.

PMID- 1372257
TI  - The effect of an immunoglobulin mu transgene on B cell maturation.
AB  - In mu 17.2.25-transgenic (M54) mice the absolute number of surface IgM (sIgM) B
      cells in lymphoid organs is drastically reduced compared to normal C57BL/6 mice
      and a high frequency of B cells express the immunoglobulin (Ig) encoded by the
      transgene rather than endogenous Ig on the surface. To determine the effect of a
      mu transgene on B cell development, adoptive cell transfers were performed using
      mu transgenic (M54) bone marrow and fetal liver cells. The data presented support
      the following conclusions: (a) adult transgenic bone marrow contains functional B
      cell precursors able to mature and repopulate the spleen and peritoneum of
      recipient mice. The relative frequency of transgene (sIgMa) and endogenous
      (sIgMb) surface sIgM-positive B cells reconstituted by transgenic bone marrow in
      allotype-matched C57BL/6 recipients is the same as in the M54 donors; (b) serum
      analysis indicates that transgenic bone marrow donor cells can reconstitute B
      cells in congenic and severe combined immunodeficient (SCID) recipient mice; (c)
      transgenic fetal liver cells are not a richer source of precursors for B cells
      expressing endogeneous Ig; (d) in transgenic mice sIgM+ B cells are not
      restricted to the CD5+ phenotype, however, the relative frequency of sIgMb B
      cells that are CD5+ is higher in transgenic than normal mice; and (e) bone marrow
      cells from adult normal and transgenic mice are able to generate CD5+ B
      lymphocytes in the spleen and peritoneum of allotype-congenic and neonatal SCID
      recipient mice. The results indicate that the presence of a complete mu heavy
      chain transgene does not result in a selective developmental block of
      "conventional" bone marrow-derived pre-B and B cells.

PMID- 1372258
TI  - Diversity of T cell receptor alpha and beta chain genes expressed by human T
      cells specific for similar myelin basic protein peptide/major histocompatibility
      complexes.
AB  - T cell receptor (TcR) alpha and beta nucleotide sequences involved in the human
      autoreactivity to myelin basic protein (MBP) were studied by screening cDNA
      libraries derived from 11 independent T lymphocyte clones (TCC) established from
      multiple sclerosis patients and healthy donors. The TCC with defined MBP peptide
      specificity and HLA-DR restriction expressed multiple TcR. Even TCC recognizing
      the same human MBP peptide [amino acids (aa) 139-153] in identical or very
      similar HLA-DR context expressed diverse TcR. Two TCC which recognized peptide aa
      139-153 equally well in the context of both HLA-DR2a and -DR1 molecules used
      distinct TcR alpha but identical beta chains. The knowledge of TcR beta and TcR
      alpha chain sequences of human MBP-specific T cells will allow studies
      correlating structure and function of TcR and their targets in MBP
      autoreactivity. This may have an impact on the development of immunotherapies in
      multiple sclerosis.

PMID- 1372259
TI  - Constraints in antigen processing result in unresponsiveness to a T cell epitope
      of hen egg lysozyme in C57BL/6 mice.
AB  - T cell hybridoma clones were derived after fusion of BW-5147 parent cells with
      lymphocytes from C57BL/6 mice injected with phosphorylcholine (PC)-hen egg
      lysozyme (HEL) conjugates. Several T cell hybridomas were preferentially reactive
      with PC-HEL over unconjugated HEL, and a particular clone (PC-H4.1) was further
      analyzed. This T cell hybridoma clone could respond to its maximal level toward
      unconjugated HEL only when the dose of HEL was increased to 5-10-fold of the PC
      HEL concentration. Interestingly, this clone was not stimulated by unfolded HEL
      (by S-carboxymethylation) to the level of PC-HEL. A synthetic peptide
      representing the amino acid position 47-61 of HEL, which is known to be non
      immunogenic upon HEL injection in C57BL/6 mice, was able to stimulate the
      hybridoma only to a level comparable to that induced by unconjugated HEL. The T
      cell response to this synthetic peptide required an additional antigen-processing
      step, based on its inability to stimulate T cells after treatment of antigen
      presenting cells with leupeptin, chloroquine or paraformaldehyde. Deletion of a
      single C-terminal amino acid residue of HEL 47-61 (arginine) significantly
      enhanced (10-100-fold of HEL 47-61) the T cell reactivity and abrogated the
      necessity of further antigen processing. These results suggest that the lack of a
      T cell response to a certain epitope may not be due to the lack of a T cell
      repertoire reactive to the epitope. In some cases, the unresponsiveness may be
      due to the difficulty in generating the particular epitopes. Taken together,
      modification of the lysozyme molecule with PC conjugation may facilitate further
      antigen processing of HEL to generate an optimal epitope for the nonresponder
      mice.

PMID- 1372260
TI  - CD59 expressed by human endothelial cells functions as a protective molecule
      against complement-mediated lysis.
AB  - CD59 is a 18-20-kDa membrane glycoprotein that inhibits formation of the membrane
      attack complex of complement (C) on homologous cells. In the present study we
      analyzed the expression and function of CD59 on human endothelial cells.
      Immunohistochemical analysis of renal cortex demonstrated a predominant
      expression of CD59 on peritubular capillary endothelial cells and glomerular
      endothelial cells. Flow cytometry analysis showed that human umbilical vein
      endothelial cells (HUVEC) expressed CD59 and the fluorescence intensity was
      approximately four times that of peripheral blood lymphocytes. CD59 is detected
      on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single 20-kDa
      molecule in 2% deoxycholate extracts of HUVEC. CD59 was released from the surface
      of HUVEC by phosphatidylinositol-specific phospholipase C, demonstrating that it
      is attached to the cell membrane by means of a glycolipid anchor. The functional
      activity of CD59 expressed on HUVEC was studied. Blocking of CD59 antigen with
      F(ab')2 fragments of polyclonal anti-CD59 enhanced markedly the susceptibility of
      HUVEC to C-mediated lysis. This effect was dependent on the amount of blocking
      antibodies added. Northern blot analysis revealed the presence of three species
      of mRNA expressed in HUVEC, which hybridized to a cDNA probe specific for CD59,
      with sizes of about 800, 1400 and 2000 bp. These findings suggest that CD59 may
      be important in protection of endothelial cells against C-mediated damage at
      local sites of inflammation, thereby maintaining the vascular integrity in vivo.

PMID- 1372261
TI  - Regulation of L-selectin expression on cultured bone marrow leukocytes and their
      precursors.
AB  - L-selectin (LECAM-1, LAM-1, MEL-14 antigen, Dreg antigen) is one of the molecules
      controlling lymphocyte homing from the blood to peripheral lymph nodes and
      granulocyte adhesion to inflamed endothelium. In this work, regulation of L
      selectin expression on mouse bone marrow cells was studied. L-selectin-negative
      cells were isolated by panning technique, cultured for 1-7 days with cytokines
      and mitogens, and L-selectin expression was analyzed by immunofluorescence
      staining. When cultured for 3 days with interleukin (IL) 1, IL 2, IL 5, IL 6,
      phytohemagglutinin, pokeweed mitogen or in the medium alone, 75%-85% of L
      selectin-negative large cells (including granulocytes, macrophages/monocytes,
      blasts and their precursors) became L-selectin positive. In contrast, IL 3, IL 4,
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide
      (LPS) prevented the induction of L-selectin in a time- and dose-dependent manner.
      GM-CSF was the most potent inhibitor and only 10%-15% of cells became L-selectin
      positive after 3 days of culture. Furthermore, L-selectin was down-regulated on
      cultured unselected bone marrow cells by IL 3, IL 4, GM-CSF and LPS stimulation.
      After culture, the relative molecular mass of L-selectin was 100 kDa, similar to
      the size of the granulocyte form of this antigen. Cultured cells adhered to high
      endothelial venules (HEV) only 10%-32% as effectively as freshly isolated bone
      marrow cells despite high levels of L-selectin expression. The phenotypic
      analysis and the HEV binding data indicate that after culturing L-selectin was
      almost exclusively expressed on bone marrow leukocytes of myeloid series, and on
      these cells it was not functional in mediating peripheral lymph node HEV binding.
      Overall, these results show that the expression of L-selectin can be modulated by
      regulating the maturation and differentiation of the cells in vitro. This
      supports the idea that different cytokines and mitogens may also be important in
      controlling migrational status of leukocytes in vivo.

PMID- 1372262
TI  - Existence of mature human CD4+ T cells with genuine class I restriction.
AB  - A human T cell receptor (TcR) alpha/beta CD4+CD8-T cell clone (R416) is reactive
      with the minor histocompatibility antigen H-Y in the context of major
      histocompatibility complex (MHC) class I and not class II molecules. Therewith
      clone R416 violates the so-called specificity association of mature TcR
      alpha/beta+ T cells. R416 displays H-Y-specific, HLA-A2-restricted proliferation
      as well as cytotoxicity in vitro. Its fine specificity is identical to that of a
      classical H-Y-reactive CD4-CD8+ MHC class I-restricted CTL clone, showing that
      CTL expressing either CD4 or CD8 can display identical antigenic specificities.
      Exploiting the MHC class I restriction of this CD4+ T cells clone, it was found
      that interaction of CD4 with non-TcR-bound MHC class II molecules does not
      contribute to antigen specific activation of these CD4+ T cells. This coreceptor
      mismatched T cell clone was not generated in vitro but obtained by expansion of
      CD8-depleted peripheral blood mononuclear cells of a female who had been
      immunized against H-Y. The existence of such MHC class I-restricted mature TcR
      alpha/beta+ T cells expressing CD4 and not CD8 is relevant because it indicates
      that the generally accepted model for thymic selection, in which the TcR
      specificity alone determines CD4/CD8 expression of mature thymocytes, may not be
      absolute.

PMID- 1372263
TI  - Ribosomal RNA gene patterns of Helicobacter pylori from surgical patients with
      healed and recurrent peptic ulcers.
AB  - Fifty-two strains of Helicobacter pylori were examined by DNA restriction
      endonuclease digestion, ribosomal (r)RNA gene probe hybridization and biotyping.
      Most (49) strains originated from gastric (antral) biopsies of patients before or
      after elective surgery for duodenal ulcers. Chromosomal DNA Hind III ribopatterns
      showed 9 strain clusters of which the largest contained 12 strains each with 3
      common bands (1.50, 3.45, and 4.26 kb) but which were heterogeneous with respect
      to biotype and total digest pattern. Isolates from post-operative patients with
      either healed or recurrent ulcers showed ribopattern heterogeneity and exhibited
      a similar distribution of H. pylori ribopattern types; no single type
      predominated in any patient group or was more highly associated with recurrent
      ulcers than with healed ulcers. Multiple isolates from two surgical patients had
      only minor genomic variations in each set whereas isolates from two brothers had
      different ribopatterns. We conclude that Hind III ribopatterns in conjunction
      with total digest patterns might provide the basis for future epidemiological
      typing studies.

PMID- 1372264
TI  - Choroidal vascular repair: scanning and transmission electron microscopy.
AB  - Repair of the choroidal vasculature following laser photocoagulation in the rat
      was examined with vascular casts and correlated with observations on thin
      sections. The regenerative process began at the periphery of the damaged area,
      starting from the surviving choriocapillaris and venules, and proceeding towards
      the center by means of recanalization of damaged vessels and growth of new ones.
      In small healed lesions the capillary bed was re-formed. It resembled the
      adjacent undamaged choriocapillaris morphologically but appeared to be less dense
      than the intact choriocapillaris when examined by scanning microscopy. In large
      lesions the capillary bed was re-formed at the periphery but not at the center.
      Also present at the edges of the large lesions were groups of new vessels which,
      when observed by scanning microscopy, appeared to extend in two directions;
      towards the subretinal space and towards the choroidal network. Another aspect of
      the repair process was the simultaneous occurrence of new vessel growth and
      capillary regression, which was observed both at the level of the
      choriocapillaris and at the foci of new vessels.

PMID- 1372265
TI  - Evaluation of the hepatotoxicological effects of a drug in an in vivo/in vitro
      model.
AB  - Both in vivo and in vitro models have certain disadvantages for the study of the
      chronic hepatotoxicity of drugs. The aim of this work was to evaluate a new
      approach based on an in vivo/in vitro model. After chronic in vivo treatment of
      rats with Vincamine and Vindeburnol (an eburnamenine derivative which exhibits
      hepatotoxic properties in man) liver cells were isolated, and functional and
      metabolic disorders (metabolic utilization of fructose and protein biosynthesis)
      were studied to determine injury. The results showed no modification of blood
      parameters, but a direct relationship between the dose of Vindeburnol
      administered in vivo and the metabolic disorders observed in vitro, evidencing
      the high sensitivity and reliability of this model.

PMID- 1372266
TI  - Correlation between car ownership and leukaemia: is non-occupational exposure to
      benzene from petrol and motor vehicle exhaust a causative factor in leukaemia and
      lymphoma?
AB  - Although there is widespread agreement that many cancers have environmental
      causes we are often unable to see associations between specific cancers and
      exposure to environmental chemicals. One might also speculate that the more
      widespread, common-place and 'normal' a chemical exposure is perceived to be then
      the less likely it will be that the exposure is recognised, let alone be
      considered to cause cancer. Widespread contamination of air by chemicals
      associated with internal combustion may be an example of one such 'invisible'
      carcinogenic exposure. Yet evidence is available which suggests that many
      leukaemia and lymphoma cases, as well as other cancers, may be caused by this
      mundane and ubiquitous environmental contamination. The hypothesis is developed
      that leukaemia 'clustering' as well as national leukaemia incidence may be
      related to non-occupational exposure to benzene formed by petrol combustion and
      resulting from petrol evaporation. The possible association between exposure to
      fuel vapours, internal combustion products and cancer merits much closer
      examination than it receives at present.

PMID- 1372268
TI  - CD1c is not a feature of mixed-cell type but of a typical form of chronic
      lymphocytic leukaemia.

PMID- 1372267
TI  - Characterization and applications of the disc angiogenesis system.
AB  - A model to study microvascular proliferation, the Disc Angiogenesis System (DAS),
      consists of a synthetic foam disc implanted subcutaneously in experimental
      animals. After a period of growth, usually 7 to 21 days, the disc is removed.
      Planar sections are used to measure and characterize the growth. Microvessels
      grow centripetally into the disc, together with fibroblasts. Concentric growth
      zones have been defined by light and electron microscopy. Moderate growth occurs
      spontaneously and is accelerated by angiogenic stimulants placed in the center of
      the disc. Morphometric analyses have shown that vessel growth is directly
      proportional to total fibrovascular growth, so the former can be quantified by
      procedures measuring the latter. These include manual projection of sections and
      computer-assisted digital image analysis, which is recommended for routine use.
      The proliferation of endothelial and other cells is determined by incorporation
      of tritiated thymidine, using scintillation counting and autoradiography. Using
      the DAS, well-established angiogenic agents such as basic fibroblast growth
      factor (bFGF), epidermal growth factor (EGF), and prostaglandin E1 were found to
      increase proliferation of endothelial cells (EC) and microvessels. Heparin
      augmented the effect of bFGF. When used by itself heparin increased angiogenesis
      but not EC proliferation, in keeping with in vitro observations indicating that
      it stimulates migration but not proliferation of EC. Locally applied hyperthermia
      and ionizing radiation decreased angiogenesis, even when applied after the
      angiogenic stimulus. Systemic prostaglandin synthetase inhibitors antagonized the
      angiogenic effects of bFGF and EGF, in accordance with a postulated role of
      prostaglandins in the transduction of proliferative signals in microvascular EC.
      The DAS is easy to assemble and implant in small animals, including mice, which
      tolerate it well. Hence multiple discs can be used for each time or dose point,
      which allows reproducible measurements of vascular growth and increases
      statistical accuracy. Another advantage of the system is the capability of
      discriminating between proliferation and migration of EC and fibroblasts. The DAS
      can be used to test putative agonists or antagonists of angiogenesis. More
      generally, the DAS provides a model of wound healing, either uncomplicated or
      complicated by inflammation, and of angiogenic responses to solid tumors.

PMID- 1372269
TI  - Intermittent rG-CSF treatment in cyclic neutropenia.

PMID- 1372270
TI  - Galanin reduces PDBu-induced protein phosphorylation in rat ventral hippocampus.
AB  - The effect of galanin (GAL) on basal and phorbol-12,13-dibutyrate (PDBu) induced
      protein phosphorylation in rat ventral hippocampal miniprisms was investigated.
      GAL (0.5, 1 and 2 microM) inhibited PDBu stimulation in a concentration-dependent
      manner without altering basal protein phosphorylation. This inhibitory effect was
      prevented by the GAL antagonist galantide. GAL did not affect either the activity
      of protein kinase C (PKC) from rat brain or basal phosphorylation in ventral
      hippocampal hippogenates, suggesting that it did not directly modulate PKC
      activity. Depolarization of miniprisms from ventral hippocampi by 18 mM K+
      prevented the effect of GAL on PDBu-induced phosphorylation. The results indicate
      that GAL indirectly regulates neuronal protein phosphorylation by a GAL receptor
      mediated action.

PMID- 1372271
TI  - Structure and RNA content of the prosomes.
AB  - Duck erythroblasts prosomes were analysed by small angle neutron scattering
      (SANS), dynamic light scattering and (cryo-)electron microscopy. A molecular
      weight of approximately 720,000 +/- 50,000, a radius of gyration of 64 +/- 2 A
      and a hydrodynamic radius of approximately 86 A were obtained. Electron
      micrographs show a hollow cylinder-like particle with a diameter of 120 A, a
      height of 170 A and a diameter of 40 A for the cavity, built of four discs, the
      two outer ones being more pronounced than those in the center. Results from SANS
      indicate less then 5% of RNA in the purified prosomes, but nuclease protection
      assays confirm its presence.

PMID- 1372272
TI  - RNase H activity of HIV reverse transcriptases is confined exclusively to the
      dimeric forms.
AB  - A method for the rapid preparation of a defined substrate to monitor RNase H
      activity has been developed. Using this substrate, we have investigated the RNase
      H activities of the different forms of recombinant HIV-1 and HIV-2 reverse
      transcriptase (RT) in detail. As we report here, RNase H activity is associated
      only with the dimeric forms (p51/p66 or p66/p66) of the enzymes.

PMID- 1372273
TI  - Divergent ileal IGF-I and IGFBP-3 gene expression after small bowel resection: a
      novel mechanism to amplify IGF action?
AB  - Changes in the levels of ileal insulin-like growth factor-I (IGF-I) and insulin
      like growth factor binding protein-3 (IGFBP-3) mRNA in the rat following massive
      small bowel resection (MSBR) have been investigated with a sensitive S1 nuclease
      assay. IGF-I mRNA levels vary little over 7 days; in contrast IGFBP-3 mRNA levels
      decreased to one-third 7 h post-MSBR, and remained suppressed for the length of
      this study. We postulate that decreased ileal synthesis of IGFBP-3 enhances the
      ability of IGF-I to stimulate the adaptive response.

PMID- 1372274
TI  - Effects of dexamethasone on the growth and epidermal growth factor receptor
      expression of the OVCA 433 ovarian cancer cells.
AB  - We studied the correlation between dexamethasone (Dex) induced growth effects and
      modulation of epidermal growth factor receptor (EGFR) expression in OVCA 433
      ovarian cancer cells. These cells express specific high and low affinity 125I-EGF
      binding sites and are growth stimulated by EGF. Dex exhibits mitoinhibitory
      effects by recruiting OVCA 433 cells in the G0-G1 phase of the cycle, but
      increases the number of both the high and the low affinity EGFR in a dose
      dependent manner. The maximal EGFR expression increase occurs after 24 h of Dex
      treatment consistently with Northern blot studies. The mitogenic activity of EGF
      in OVCA 433 cells is not affected by the presence of Dex. Moreover Dex growth
      inhibition occurs in JA1 cells, an ovarian cancer cell line which expresses
      unfunctional EGFR and which is unresponsive to EGF. Our results indicate that the
      Dex induced growth effects occur independently of EGFR expression.

PMID- 1372275
TI  - Assembly and expression of a synthetic gene encoding the bovine glycoprotein
      hormone alpha-subunit.
AB  - The glycoprotein hormones are a family of alpha beta heterodimeric proteins which
      are responsible for gonadal and thyroid function. In previous studies we employed
      chimeric glycoprotein hormone beta-subunits to identify amino acid residues
      critical for binding to receptors and antibodies. To facilitate similar studies
      of the alpha-subunit of these hormones, we assembled a 406 bp synthetic gene
      which encodes the human alpha-subunit leader sequence and the secreted portion of
      the bovine alpha-subunit. It contains unique restriction sites that can be used
      for cassette mutagenesis or for making human/bovine alpha-subunit chimeras. The
      gene was assembled from eight long oligodeoxynucleotides in a single ligation and
      its structure verified by DNA sequencing. Co-transfection of COS-7 cells with the
      synthetic gene and the cDNA for human chorionic gonadotropin (hCG) beta-subunit
      resulted in the secretion of a functional alpha beta heterodimer which bound to
      luteinizing hormone receptors. The protein was recognized by several monoclonal
      antibodies including B109, an antibody to a conformational epitope which binds
      hCG but not the free bovine alpha-, human alpha-, or hCG beta-subunits. This
      suggests that the binding site for B109 may be formed by residues located
      primarily within the hCG beta-subunit and that formation of this epitope requires
      a change in conformation of the beta-subunit when it combines with the alpha
      subunit.

PMID- 1372276
TI  - Expression of an activated Notch-related int-3 transgene interferes with cell
      differentiation and induces neoplastic transformation in mammary and salivary
      glands.
AB  - Expression of the int-3 locus is activated in mouse mammary tumors as a
      consequence of insertional mutagenesis by the mouse mammary tumor virus (MMTV).
      Integration of the MMTV provirus into the int-3 locus promotes the transcription
      and translation of flanking cellular int-3 sequences sharing significant homology
      with the intracellular domain of the neurogenic Notch gene of Drosophila, and
      with the yeast cell cycle regulatory genes cdc10 and SWI6. To determine the in
      vivo consequences of activated int-3 expression, transgenic mice were generated
      harboring a genomic tumor DNA fragment consisting of the MMTV LTR and the
      flanking cellular int-3 sequences. All six int-3 founder transgenic mice and the
      progeny of one established line exhibited similar dramatic phenotypic
      abnormalities in tissues in which the transgene was expressed. Focal and often
      multiple poorly differentiated mammary and salivary adenocarcinomas appeared in
      the majority of transgenic mice between 2 and 7 months of age. Significantly,
      mammary glands were arrested in development and were lactation deficient in all
      female int-3 mice. The salivary glands, glands of the nasal mucosa and maxillary
      sinus, the extraorbital lacrimal glands, and the Harderian glands of juvenile and
      adult transgenic mice all contained proliferating immature ductule cells and were
      incompletely differentiated. In addition, all male int-3 transgenic mice were
      sterile, apparently the result of severe hyperplasia of the epididymis. These
      findings demonstrate in vivo that expression of the activated Notch-related int-3
      gene causes deregulation of normal developmental controls and hyperproliferation
      of glandular epithelia.

PMID- 1372277
TI  - csgA expression entrains Myxococcus xanthus development.
AB  - The development cycle of the myxobacterium Myxococcus xanthus consists of three
      partially overlapping morphological stages referred to as rippling, fruiting body
      formation, and sporulation, all of which are absent in csgA null mutants. The
      CsgA gene product is an extracellular protein, referred to as the C signal, which
      is essential for developmental cell-cell interactions. csgA expression increases
      throughout development, reaching its peak during sporulation. CsgA was made
      limiting for development by constructing nested deletions upstream from the csgA
      gene, which resulted in reduced csgA expression. Successively larger deletions
      resulted in termination of development at earlier and earlier stages, with
      rippling requiring approximately 20% maximum csgA expression, fruiting body
      formation requiring approximately 30% expression, and sporulation requiring 82%
      expression. Conversely, artificial induction of csgA also induced development
      provided nutrients were limiting. These results suggest that steady increases in
      CsgA over the course of development entrain the natural sequence of morphological
      events. The csgA upstream region appears to process information concerning the
      levels of nutrients, peptidoglycan components, and the B signal. In the absence
      of nutrients, a region extending 400 bp upstream from the start site of
      transcription was necessary for development and maximal csgA expression. In the
      presence of low levels of nutrients, a region extending approximately 930 bp
      upstream was essential for the same tasks. It appears that the upstream region
      extending from -400 to -930 stimulates csgA expression in the presence of excess
      carbon, nitrogen, and phosphate, thereby allowing development to go to
      completion.

PMID- 1372278
TI  - The Rex system of bacteriophage lambda: tolerance and altruistic cell death.
AB  - The rexA and rexB genes of bacteriophage lambda encode a two-component system
      that aborts lytic growth of bacterial viruses. Rex exclusion is characterized by
      termination of macromolecular synthesis, loss of active transport, the hydrolysis
      of ATP, and cell death. By analogy to colicins E1 and K, these results can be
      explained by depolarization of the cytoplasmic membrane. We have fractionated
      cells to determine the intracellular location of the RexB protein and made RexB
      alkaline phosphatase fusions to analyze its membrane topology. The RexB protein
      appears to be a polytopic transmembrane protein. We suggest that RexB proteins
      form ion channels that, in response to lytic growth of bacteriophages, depolarize
      the cytoplasmic membrane. The Rex system requires a mechanism to prevent lambda
      itself from being excluded during lytic growth. We have determined that
      overexpression of RexB in lambda lysogens prevents the exclusion of both T4 rII
      mutants and lambda ren mutants. We suspect that overexpression of RexB is the
      basis for preventing self-exclusion following the induction of a lambda lysogen
      and that RexB overexpression is accomplished through transcriptional regulation.

PMID- 1372279
TI  - Analysis of a ribosomal RNA operon in the actinomycete Frankia.
AB  - The organisation of ribosomal RNA-encoding (rrn) genes has been studied in
      Frankia sp. strain ORS020606. The two rrn clusters present in Frankia strain
      ORS020606 were isolated from genomic banks in phage lambda EMBL3 by hybridization
      with oligodeoxyribonucleotide probes. The 5'-3' gene order is the usual one for
      bacteria: 16S-23S-5S. The two clusters are not distinguishable by restriction
      enzyme mapping inside the coding section, but vary considerably outside it.
      Sequencing showed that the 16S-rRNA-encoding gene of ORS020606 is very closely
      related to that of another Alnus-infective Frankia strain (Ag45/Mut15) and highly
      homologous to corresponding genes of Streptomyces spp. Two possible promoter
      sequences were detected upstream from the 16S gene, while no tRNA-encoding gene
      was detected in the whole operon. Regions with a high proportion of divergence
      for the study of phylogenetic relationships within the genus were looked for and
      found in the first intergenic spacer, in the 23S and in the 16S gene.

PMID- 1372280
TI  - Interaction between viruses and monoclonal antibodies studied by surface plasmon
      resonance.
AB  - An automated biosensor system designed for measuring molecular interactions in
      real time and without any labelling of the reactants has been used to study the
      interaction of two animal viruses (vaccinia virus and poliovirus) and two plant
      viruses (cowpea mosaic virus and tobacco mosaic virus) with monoclonal
      antibodies. Using monoclonal antibodies specific for different conformational
      states of viral protein, it was found that the virus particles retained their
      conformational integrity when immobilized on the dextran matrix present on the
      sensor chip. Compared to conventional solid phase immunoassays, in which
      immobilized proteins are usually partly denatured, the biosensor system presents
      several advantages for studying virus-antibody interaction.

PMID- 1372281
TI  - A crude extract of Artocarpus integrifolia contains two lectins with distinct
      biological activities.
AB  - The crude extract derived from seeds of Artocarpus integrifolia (jack fruit)
      contains two fractions with different biological activities for lymphocytes. One
      fraction is the D-galactose-binding lectin, jacalin, obtained by affinity
      purification on a D-galactose agarose column. The other, which is a component of
      the flow-through fraction (FT), is responsible for the mitogenic activity
      observed with human PBMC and murine spleen cells. In contrast, jacalin inhibits
      FT- and ConA-induced proliferative activity of human PMBC and murine spleen
      cells. This inhibition is not due to toxicity, because: (1) jacalin induces
      significant levels of IL-3/GM-CSF but not of IL-2 and/or IL-4 in murine spleen
      cells; (2) jacalin does not affect the capacity of these cells to secrete IL-2 or
      IL-4 as supernatants obtained from spleen cells sequentially stimulated with
      jacalin and ConA contain IL-2 and/or IL-4 as well as IL-3/GM-CSF. The ligand for
      the mitogen contained in the FT fraction is D-mannose as determined by sugar
      inhibition studies.

PMID- 1372282
TI  - Cell-free CD5 in patients with rheumatic diseases.
AB  - Since an increased frequency of CD5+ B cells has been reported in rheumatoid
      arthritis (RA) and primary Sjogren's syndrome (SS), and the expression of the
      molecule was reduced on the T cells of some SS patients, we hypothesised that
      there would be an accelerated turnover of CD5 in these disorders. We describe a
      novel enzyme-linked immunosorbent assay for measuring cell-free (CF) CD5, using
      rabbit F(ab')2 anti-CD5 antibody as capture agent and monoclonal anti-CD5
      antibody as revealing agent. It was established that CF-CD5 was detectable in RA
      and SS sera, as opposed to sera from patients with ankylosing spondylitis and
      normal controls. The level of CF-CD5 did not correlate with rheumatoid factor in
      RA patients but was significantly higher (P less than 0.05) in SS patients with
      extraglandular manifestations than in those with glandular disease. Three of the
      latter patients with significantly increased levels of CD5-negative T cells did
      not have a particularly high proportion of CF-CD5 in these sera.

PMID- 1372283
TI  - Activation of human natural killer cells by the protein-bound polysaccharide PSK
      independently of interferon and interleukin 2.
AB  - The protein-bound polysaccharide PSK was tested for the ability to activate human
      natural killer (NK) cells. When blood lymphocytes and purified CD3-CD16+ large
      granular lymphocytes (LGL) were treated in vitro overnight with PSK, they
      demonstrated enhanced NK cell activity against K562. The PSK-activated killer
      cells also lysed NK-resistant targets and freshly isolated autologous and
      allogeneic tumor cells. The PSK effect was observed with concentrations that
      could be obtained in the blood of cancer patients receiving oral administration
      of PSK. PSK-induced enhancement of NK activity was not abrogated by monoclonal
      antibodies (mAb) that neutralized interferon (IFN) alpha, IFN gamma, or
      interleukin-2 (IL-2). In addition, mAb reactive with p55 (alpha chain) or p75
      (beta chain) glycoproteins of IL-2 receptors had no effects on PSK-enhanced NK
      activity even when used simultaneously. These results indicate that the PSK could
      activate human NK cells independently of IFN and IL-2/IL-2R systems.

PMID- 1372284
TI  - Expression of CD54, CD58, CD14, and HLA-DR on macrophages and macrophage-derived
      accessory cells and their accessory capacity.
AB  - Human peripheral monocytes can differentiate in vitro into macrophages (Mph)
      possessing a low accessory activity in T cell stimulation. Mph can be converted
      into a state of high accessory activity by treatment with dibutyryl cyclic AMP.
      This finding was used in this study to achieve Mph-derived AC (MphAC). Among the
      surface antigens on AC which have been shown to participate in accessory events
      leading to T cell proliferation, MHC class II antigens, CD58 (LFA-3) and CD54
      (ICAM-1) seem to be especially important. We show here that the high accessory
      capacity of MphAC was not correlated with a high level of the surface antigens
      HLA-DR, CD58, and CD54. The amount of CD54 molecules was, in fact, lower on the
      MphAC than on the Mph.

PMID- 1372285
TI  - Cleavage of human immunoglobulins by serine proteinase from Staphylococcus
      aureus.
AB  - The serine proteinase (SP) released into the environment by most strains of S.
      aureus cleaves human IgG, IgM and IgA of both subclasses--IgA 1 and IgA 2. SP
      cleaves H chains of all immunoglobulin classes and the SC of S-IgA, the L chains
      are degraded partially. The SP-induced cleavage results in a large spectrum of
      fragments under reducing conditions within a broad range of Mr (approx. 41,000 to
      less than 12,400). This indicates that the enzyme does not affect the Ig molecule
      in the hinge region only. The degree of cleavage depends on the enzyme:substrate
      ratio and on the duration of incubation. The generation of small fragments is
      associated with the loss of antigenic determinants that results from the
      decreased binding of the cleaved material in the ELISA method. Partial cleavage
      of L chains suggests that the enzyme alters part of the molecule that is involved
      in antigen binding. Even if the ability of antigen binding remains preserved
      after cleaving Ig with SP, the antibody function is disturbed by splitting off
      the Fc region or by its degradation into small fragments. SP has to be considered
      as one of the virulence factors of S. aureus that may protect bacteria against
      the defence mechanisms of the host.

PMID- 1372286
TI  - Molecular cloning of the bovine thymopoietin gene and its expression in different
      calf tissues: evidence for a predominant expression in thymocytes.
AB  - Thymopoietin (TP), a 49 amino acid peptide, is regarded as a thymic hormone,
      secreted specifically by some epithelial cells in the thymic stroma and exerting
      a multitude of effects on maturation and function of T lineage cells. As part of
      our study on the molecular biology of TP, we isolated cDNA clone coding for a
      bovine TP precursor and used it as a probe to analyze the presence of mRNA coding
      for TP in different tissues. The cDNA clone reported here is 1.1 kb long and
      contains an open reading frame (ORF) of 741 bp which corresponds to 247 amino
      acids. The 147 bp coding for the entire bovine TP are at the 5' end of the ORF. A
      DNA fragment coding for amino acids 1-42 of bovine TP was used as a probe to look
      for hybridizable RNA sequences, extracted from various calf tissues, by the S1
      nuclease protection method. Our results indicate that the TP gene is expressed
      predominantly in lymphatic tissues. Lymphatic tissues with the highest levels
      observed were thymocytes and not thymic stroma. Lower, but still significant,
      amounts were present in tonsils, neck lymph nodes, and small intestine (probably
      because of its lymphatic part--the Peyer's patches), whereas cultured thymic
      stromal cells, spleen tissue and peripheral blood mononuclear cells displayed a
      low level of TP mRNA. The TP gene expression in all other (non-lymphatic) tissues
      tested, was weak, barely detectable or virtually absent. However, the cerebellum
      could be singled out with relatively strong expression of TP mRNA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1372287
TI  - Culture-associated enhancement of LECAM-1 expression by lymphocytes and partial
      inhibition of enhancement by IL-4.
AB  - Recent studies have shown that the human leukocyte endothelial cell adhesion
      molecule-1 (LECAM-1) functions as a homing receptor, mediating leukocyte binding
      to high endothelial venules in peripheral lymph nodes. Increasing evidence has
      demonstrated that cytokines, such as IL-4, can modulate the expression of surface
      proteins such as homing receptors on a variety of cells. We thus investigated the
      modulatory effects of cytokines on LECAM-1 expression by lymphocytes using single
      and dual-color flow cytometry. We found that the density of LECAM-1 expression
      increased markedly during 3 days of culture and that this culture-associated
      enhancement (CAE) of LECAM-1 expression was significantly inhibited by IL-4. B
      cells and both major T cell subsets (CD4, CD8) exhibited CAE of LECAM-1
      expression, but the inhibitory effect of IL-4 on this response occurred only in
      the T cell populations. The inhibitory effect of IL-4 on enhanced LECAM-1
      expression was reversible, and characterized all 3 LECAM-1 epitopes assessed.
      Natural killer cells, in contrast, did not exhibit CAE of LECAM-1 expression, and
      IL-4 had no modulatory effect on LECAM-1 expression by these cells. Another
      adhesion molecule, CD44, showed enhanced expression during culture, but this
      enhancement was not inhibited by IL-4. The results show that LECAM-1 expression
      by T and B lymphocytes is significantly increased during culture and that the
      inhibitory effect of IL-4 on this increase is restricted to T cells. These
      findings suggest that IL-4, generated during an immune response, may play a role
      in regulating the migration and localization of T lymphocytes to lymphoid
      tissues.

PMID- 1372288
TI  - Aldosterone regulation of gene transcription leading to control of ion transport.
AB  - Aldosterone, like other steroid hormones, initiates its effects by binding to
      intracellular receptors; these receptors are then able to control the
      transcription of several genes. The products of these genes eventually modulate
      the activity of ionic transport systems located in the apical and the basolateral
      membrane of specialized epithelial cells, thereby modulating the excretion of Na+
      and K+ ions. Considerable progress has been made recently in understanding these
      mechanisms and the structure of the proteins involved in these processes. A novel
      principle has been discovered to explain the selective effect of aldosterone on
      its target epithelia. These tissues exclude competing glucocorticoid hormones by
      the activity of the 11 beta-hydroxysteroid dehydrogenase to allow aldosterone, an
      enzyme-resistant steroid, to bind to its receptors. Aldosterone induces numerous
      changes in the activity of membrane ion transport systems and enzymes and cell
      morphology. Although the enhancement of Na,K-ATPase synthesis and the increase of
      the number of active Na+ channels in the apical membrane appear as both direct
      and primary effects, the mechanisms of the other effects remain to be determined.
      The knowledge of the primary structure of several elements of the aldosterone
      response system (e.g., mineralocorticoid receptor and Na,K-ATPase) allows us to
      understand abnormal regulation of Na+ balance at the molecular level and,
      potentially, to identify genetic alterations responsible for these defects.

PMID- 1372289
TI  - Quantitation of hypothalamic atrial natriuretic peptide messenger RNA in
      hypertensive rats.
AB  - Previous studies from our laboratory have shown that spontaneously hypertensive
      rats have increased atrial natriuretic peptide stores and reduced norepinephrine
      release from nerve terminals in the anterior hypothalamus. We have postulated
      that atrial natriuretic peptide inhibits norepinephrine release in anterior
      hypothalamus, reducing excitation of sympathoinhibitory neurons, increasing
      sympathetic outflow, and elevating blood pressure in this model. The current
      study tested the hypothesis that atrial natriuretic peptide messenger RNA (mRNA)
      transcript levels are increased in anterior hypothalamus of spontaneously
      hypertensive rats compared with normotensive Wistar-Kyoto rats. Atrial
      natriuretic peptide mRNA in hypothalamic regions was measured by the quantitative
      polymerase chain reaction technique using a p-SELECT mutant atrial natriuretic
      peptide RNA as an internal standard. Atrial natriuretic peptide mRNA from
      hypothalamic regions of spontaneously hypertensive and Wistar-Kyoto rats and the
      internal standard were coamplified in a single reaction in which the same primers
      were used. Since the polymerase chain reaction product of the internal standard
      contained a new EcoRI restriction site, it could be distinguished from the atrial
      natriuretic peptide mRNA product by EcoRI digestion after the polymerase chain
      reaction. We found regional inhomogeneity of atrial natriuretic peptide mRNA in
      the hypothalamus of spontaneously hypertensive and Wistar-Kyoto rats, but we
      found no significant differences in atrial natriuretic peptide mRNA levels in
      anterior, posterior, or ventral hypothalamic areas between spontaneously
      hypertensive rats and Wistar-Kyoto rats fed normal (1%) or high (8%) salt diets.
      These data do not support the hypothesis that increased atrial natriuretic
      peptide stores in anterior hypothalamus of spontaneously hypertensive rats are
      related to increased gene transcription.

PMID- 1372290
TI  - A synthetic glycoconjugate representing the genus-specific epitope of chlamydial
      lipopolysaccharide exhibits the same specificity as its natural counterpart.
AB  - The tetrasaccharide 3-deoxy-alpha-D-manno-2-octulosonic acid (alpha-KDO) (2----8)
      alpha-KDO(2----4)-alpha-KDO(2----6)-beta GlcNAc, a partial structure of
      chlamydial lipopolysaccharide (LPS) representing a genus-specific epitope, was
      synthesized and covalently linked to bovine serum albumin, resulting in an
      artificial glycoconjugate antigen. Mice were immunized with the glycoconjugate to
      prepare chlamydia-specific monoclonal antibodies. They were selected with
      chlamydia-specific LPS antigens and the structurally and antigenically related Re
      type LPS of a Salmonella minnesota rough mutant. Characterization of the selected
      antibodies was by (i) hemagglutination of sheep erythrocytes coated with
      recombinant chlamydia-specific LPS, (ii) inhibition by synthetic polyacrylamide
      derivatives containing the genus-specific epitope or partial structures thereof,
      (iii) enzyme immunoassay with recombinant LPS and synthetic bovine serum albumin
      glycoconjugates as solid-phase antigens, (iv) immunofluorescence of L929
      monolayers infected with Chlamydia psittaci or C. trachomatis, and (v) Western
      immunoblots with glycoconjugates and LPS as the antigen. Two groups of monoclonal
      antibodies were obtained; the monoclonal antibodies in one group cross-reacted
      with chlamydial and Re-type LPS, but those of the other group were chlamydia
      specific. Among the latter, KDO trisaccharide-specific antibodies that had the
      same epitope specificity as antibodies obtained after immunization with
      chlamydial elementary bodies were identified; however, they exhibited a more than
      100-fold higher affinity. In addition, antibodies that bound preferentially to
      the 2.8-linked KDO disaccharide were detected, although with lower affinity. The
      data show that the artificial glycoconjugate antigen is similar to its natural
      counterpart.

PMID- 1372291
TI  - Lipooligosaccharides (LOS) of some Haemophilus species mimic human
      glycosphingolipids, and some LOS are sialylated.
AB  - The lipooligosaccharides (LOS) of strains of Haemophilus ducreyi, Neisseria
      gonorrhoeae, Neisseria meningitidis, and Neisseria lactamica contain epitopes
      that are antigenically and structurally similar to carbohydrates present in human
      glycosphingolipids. LOS from strains of Haemophilus influenzae and H. influenzae
      biogroup aegyptius were tested for the binding of monoclonal antibodies (MAbs)
      that bind to human glycosphingolipids possessing Gal beta 1-4GlcNAc (MAb 3F11)
      and Gal alpha 1-4Gal beta 1-4Glc (MAb anti-Pk). In solid-phase radioimmunoassays,
      the LOS of 18 of 19 H. influenzae type b (Hib), 8 of 19 nontypeable H.
      influenzae, and 10 of 20 H. influenzae biogroup aegyptius strains bound MAb anti
      Pk. The LOS of 13 of 19 Hib, 10 of 16 nontypeable H. influenzae, and 2 of 18 H.
      influenzae biogroup aegyptius strains bound MAb 3F11. Neuraminidase treatment of
      the strains increased the binding of MAb 3F11 by more than twofold in 47% of the
      H. influenzae strains, suggesting that sialic acid occluded the LOS structure
      recognized by MAb 3F11. The material released from neuraminidase-treated Hib LOS
      was confirmed to be sialic acid by high-performance anion-exchange
      chromatography. A recombinant plasmid containing genes involved in Hib LOS
      biosynthesis directed the expression (assembly) of the 3F11 epitope in
      Escherichia coli. These studies demonstrate that H. influenzae and H. influenzae
      biogroup aegyptius express at least two LOS epitopes that are similar to those
      present in human glycosphingolipids. Sialic acid was present on the LOS of some
      H. influenzae strains and prevented the binding of MAb 3F11 to its epitope. The
      oligosaccharide portion of sialylated LOS may also resemble sialylated
      oligosaccharides present in human glycosphingolipids (gangliosides).

PMID- 1372293
TI  - Stable, conserved outer membrane epitope of strains of Haemophilus influenzae
      biogroup aegyptius associated with Brazilian purpuric fever.
AB  - Brazilian purpuric fever is a rapidly fatal childhood disease associated with a
      clonal strain of Haemophilus influenzae biogroup aegyptius. We describe a
      conserved, surface-exposed epitope present on 95% of H. influenzae biogroup
      aegyptius isolates that are associated with Brazilian purpuric fever. This
      epitope, defined by reaction with the monoclonal antibody 8G3, is on or
      associated with the 48-kDa heat-modifiable P1 protein. The epitope is absent on
      strains of H. influenzae biogroup aegyptius that are not associated with
      Brazilian purpuric fever but is present on one strain of H. influenzae biotype
      II. None of 81 other Haemophilus strains tested reacted with 8G3. The sensitivity
      and specificity of the 8G3 monoclonal antibody in detecting Brazilian case-clone
      strains of H. influenzae biogroup aegyptius associated with Brazilian purpuric
      fever are 95 and 99%, respectively. Immunoelectron microscopy revealed that the
      epitope is surface exposed, and N-terminal amino acid sequencing of an 8G3
      reactive P1 protein from a strain of H. influenzae biogroup aegyptius showed 100%
      correlation with the published N-terminal amino acid sequence of a P1 protein of
      H. influenzae type b. The virulence of the organism in an infant rat model of
      bacteremia was not dependent on the expression of this epitope.

PMID- 1372292
TI  - Role of energy metabolism in conversion of nonmucoid Pseudomonas aeruginosa to
      the mucoid phenotype.
AB  - Phosphatidylcholine, the major component of lung surfactant, when supplied as the
      sole source of phosphate for Pseudomonas aeruginosa PAO1, resulted in conversion
      of as much as 2% of the population to the mucoid phenotype under continuous
      culture conditions over a 24-day culture period. In addition, growth in
      phosphatidylcholine resulted in the highest yields of extracellular alginate
      compared with other environmental conditions. Iron limitation, another
      environmental condition relevant to the lungs of patients with cystic fibrosis,
      also resulted in conversion to mucoid. Since both conditions suggested the
      likelihood of an energy-deprived growth environment as a common variable, the
      effect of direct inhibition of energy generation by N,N'-dicyclohexylcarbodiimide
      or gramicidin on the conversion of nonmucoid P. aeruginosa to the mucoid
      phenotype was examined. Both inhibitors resulted in mucoid subpopulations (0.5
      and 0.8%, respectively). Severe energy stress imposed by the combination of
      phosphate limitation and N,N'-dicyclohexylcarbodiimide treatment resulted in
      conversion of 55% of the population to mucoidy during a 7-day growth period. A
      growth advantage of the mucoid over the nonmucoid phenotype was observed under
      severe nutrient deprivation by growth on unsupplemented Noble agar or in a
      1/2,500 dilution of a chemically defined medium. These results clearly
      demonstrate a significant role for the energy state of the cell in conversion to
      mucoid and in selection for the mucoid phenotype.

PMID- 1372294
TI  - Isolation and characterization of recombinant antigens from Leishmania aethiopica
      that react with human antibodies.
AB  - A genomic expression library of Leishmania aethiopica was constructed in lambda
      gt11 and screened with patient sera and sera from healthy people living in an
      area of endemicity. Forty-five recombinant clones were isolated and partly
      characterized. Clone-specific antibodies were prepared and used with sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblot
      analysis to estimate the molecular masses of the parasite-derived antigens
      containing the reactive epitope(s). Antigens with apparent molecular masses of
      90, 85, 63, 50, 41, 25 and 24 kDa as well as several antigens with lower
      molecular masses were detected. The clone-specific antibodies from patients with
      diffuse cutaneous leishmaniasis reacted with high-molecular-weight antigens
      (30,000 less than Mr less than 90,000), whereas antibodies from patients with
      localized cutaneous leishmaniasis recognized low-molecular-weight antigens (Mr
      less than 25,000). Nine different purified recombinant antigens were obtained
      from lysogens in Escherichia coli Y1089 by immunoaffinity chromatography on anti
      beta-galactosidase columns and were subsequently tested with patient sera. It is
      suggested that some of these recombinant antigens might be used for
      immunodiagnostic purposes.

PMID- 1372295
TI  - Identification of the mucin-binding adhesin of Pseudomonas cepacia isolated from
      patients with cystic fibrosis.
AB  - In previous experiments, we have shown that isolates of Pseudomonas cepacia from
      sputa of patients with cystic fibrosis (CF), particularly those with severe lung
      infection, exhibited specific binding to purified respiratory or intestinal
      mucins (U. Sajjan, M. Corey, M. Karmali, and J. Forstner, J. Clin. Invest. 89:648
      656, 1992). The present report describes the identification of the adhesin as a
      protein located on fimbriae of mucin-binding P. cepacia. From a total of 53
      isolates available (from 22 patients with CF), we used three mucin-binding and
      three non-mucin-binding isolates for our experiments. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of crude P. cepacia homogenates was performed,
      the separated proteins were blotted onto nitrocellulose and overlaid with
      purified mucin, and mucin-binding components were detected with an antimucin
      antibody and then a second-antibody-alkaline phosphatase conjugate system. Only
      mucin-binding isolates exhibited a positively stained band at an Mr of 22,000.
      The 22-kDa protein was purified, and a polyclonal antibody specific for it was
      developed in rabbits. By electron microscopy and immunogold labelling, both the
      antibody and mucin (separately) were localized to pili present over the entire
      surface of the bacterial cells. Non-mucin-binding isolates did not have (or had
      very few) pili and did not stain with either mucin or the antibody to the 22-kDa
      protein. The purified 22-kDa protein and its antibody were each able to inhibit
      piliated P. cepacia binding to mucin. The amino acid composition of the 22-kDa
      protein was dissimilar to those of the major pilin proteins of Escherichia coli
      (type 1 pilus) and P. aeruginosa (PAK and PAO1 strains). Both the pili of P.
      aeruginosa PAK and PAO1 and antibodies to these pili failed to inhibit P. cepacia
      binding to mucin. Thus, P. cepacia adhesion to mucin is mediated by a pilin
      associated 22-kDa protein which differs from epithelial-cell-binding pilin
      proteins of P. aeruginosa. We postulate that the 22-kDa adhesin may play a role
      in the virulence of P. cepacia lung infections of patients with CF.

PMID- 1372296
TI  - Porphyromonas gingivalis fimbriae induce expression of the neutrophil chemotactic
      factor KC gene of mouse peritoneal macrophages: role of protein kinase C.
AB  - To account for infiltration of the periodontal tissues by neutrophils, the
      present study was undertaken to examine whether Porphyromonas gingivalis
      fimbriae, important structures involved in attachment of the bacteria to
      periodontal tissues, induce gene expression of the neutrophil chemoattractant KC
      in macrophages. The fimbriae induced expression of the KC gene of mouse
      peritoneal macrophages in a dose-dependent fashion. The peak of KC gene
      expression was observed as early as 1 h after initiation of the treatment.
      However, the gene expression was short lived, with the expression decreasing
      gradually after 6 h. A nuclear transcriptional assay showed that the fimbriae
      regulated the KC gene expression at a posttranscriptional level. We observed that
      the fimbria-induced KC gene expression was not regulated by endogenous or
      exogenous prostaglandin. Furthermore, forskolin, a potent activator of adenyl
      cyclase, and dibutyryl cyclic AMP were incapable of inducing KC gene expression
      of the peritoneal macrophages. H-8 and HA 1004, inhibitors of cyclic nucleotide
      dependent protein kinases, had little effect on the fimbria-induced KC gene
      expression. On the other hand, the fimbria-induced KC gene expression was
      inhibited markedly by treatment with H-7, a potent inhibitor of protein kinase C.
      We also observed that phorbol 12-myristate 13-acetate, a specific activator of
      protein kinase C, induced KC gene expression of peritoneal macrophages in a dose
      dependent fashion. In addition, the fimbria-induced KC gene expression was
      suppressed in the peritoneal macrophages pretreated for 24 h with phorbol 12
      myristate 13-acetate. These results suggest that the KC gene expression was
      mediated through activation of protein kinase C and not through that of cyclic
      nucleotide-dependent protein kinases. The present study indicates that P.
      gingivalis fimbriae can induce gene expression of the neutrophil chemotactic
      factor KC by macrophages via protein kinase C and suggests that this factor may
      be involved in infiltration of neutrophils into the periodontal tissues of adult
      periodontal patients.

PMID- 1372297
TI  - Analysis of the N-terminal region of the 47-kilodalton integral membrane
      lipoprotein of Treponema pallidum.
AB  - The 47-kDa lipoprotein is an abundant integral membrane protein and dominant
      immunogen of Treponema pallidum subsp. pallidum. Previous DNA sequencing of the
      47-kDa-lipoprotein gene did not reveal consensus features representative of other
      bacterial lipoprotein genes; this prompted further analyses with emphasis on
      elucidation of the N terminus of the molecule. To assist in localizing start
      signals for the protein, the transcription initiation site for the 47-kDa-antigen
      gene was determined. RNA isolated from both T. pallidum and recombinant
      Escherichia coli expressing the 47-kDa antigen was used as a template in reverse
      transcriptase primer extension. Upon analysis of cDNA products, transcription
      initiation was localized to one nucleotide in T. pallidum and to two adjacent
      nucleotides in E. coli. When various primers were used in DNA sequencing
      reactions for these analyses, a previously undetected nucleotide (G) was found in
      the purported 5' untranslated region; this altered the upstream reading frame to
      reveal plausible sites for ribosome binding (GGAGG), translation initiation (GTG
      start codon), and signal peptidase II processing (Val-Val-Gly-Cys). Discounting
      acylation, the molecular weight of the mature polypeptide is 45,756
      (approximately 46,600 with acylation). To derive nonacylated 47-kDa antigen for
      further structure-function studies, the 47-kDa-antigen gene was subcloned without
      acylation signals as a genetic construct encoding a glutathione S-transferase
      fusion protein; following cleavage with thrombin, the nonacylated 47-kDa protein
      was hydrophilic rather than amphiphilic but retained its antigenicity when tested
      against 116 human serum samples from patients with various stages of syphilis.

PMID- 1372298
TI  - Outer membrane protein patterns mark clones of Escherichia coli O2 and O78
      strains that cause avian septicemia.
AB  - Major outer membrane proteins were isolated from 36 Escherichia coli strains
      representing six common clones of the O2 and O78 serogroups implicated in avian
      colisepticemia. Clonal relationships among isolates were inferred from an
      analysis of polymorphism at 20 enzyme-encoding loci detected by multilocus enzyme
      electrophoresis. For isolates of these clones, there was a high concordance
      (greater than 90%) between identity in multilocus genotype and major outer
      membrane protein patterns. The results indicate that major outer membrane protein
      patterns discriminate among the genetically different clonal groups that
      constitute the heterogeneous O2 and O78 serogroups associated with avian disease.

PMID- 1372299
TI  - Neutralization-sensitive epitopes are conserved among geographically diverse
      isolates of Cryptosporidium parvum.
AB  - Isolates of Cryptosporidium parvum from New York, Florida, Brazil, Mexico, and
      Peru were examined for the presence of two sporozoite surface epitopes originally
      identified in an Iowa isolate by neutralizing monoclonal antibodies (MAbs) 18.44
      and 17.41. Immunofluorescence microscopy and immunoblotting demonstrated the
      presence of both epitopes on all isolates. Incubation of DEAE-cellulose-purified
      sporozoites of the New York, Florida, Brazil, and Mexico isolates with MAb 18.44
      or 17.41 significantly neutralized their infectivity for 4- to 6-day-old BALB/c
      mice. The results indicate that two neutralization-sensitive epitopes are
      conserved on geographically diverse C. parvum isolates.

PMID- 1372301
TI  - Ventricular arrhythmias in aortic valve disease: a further marker of impaired
      left ventricular function.
AB  - One hundred and twenty stable patients with pure and severe aortic valve disease
      and without coronary lesions (aortic stenosis, 43 patients; aortic regurgitation,
      45 patients; combined aortic stenosis and regurgitation, 32 patients) who had
      been submitted to haemodynamic studies were prospectively studied with standard
      electrocardiograms, M-mode echocardiograms, and 24-hour ambulatory
      electrocardiography (Holter recording). The frequency and complexity of
      ventricular arrhythmias were related to clinical parameters such as functional
      class, type of lesion and presence of syncope, and to parameters of left
      ventricular hypertrophy and function. Ventricular arrhythmias were present in 92%
      of patients. A high number of ventricular premature beats was directly correlated
      with parameters of complexity of the arrhythmia. A significant relation was found
      between electrocardiographic left ventricular hypertrophy and Ryan class (P less
      than 0.05), and an inverse relation between maximal number of ventricular
      premature beats in any hour and left ventricular ejection fraction (P less than
      0.05). The group of patients with aortic regurgitation showed a higher total
      number of ventricular premature beats per 24 hours (P less than 0.001), a higher
      maximal number of these in any hour (P less than 0.01), a higher number of
      patients with pairs (P less than 0.001), and a higher number of patients in Ryan
      classes 3, 4A, 4B (P less than 0.01). This study shows a high incidence of
      ventricular arrhythmias in aortic valve disease, and especially in aortic
      regurgitation, with a significant relation between left ventricular hypertrophy
      and function, and number and complexity of arrhythmias.

PMID- 1372300
TI  - The circadian profile of extrasystolic arrhythmia: its relationship to heart rate
      and blood pressure.
AB  - This paper aims at examining whether there is an association between the
      circadian patterns of systolic blood pressure, heart rate and the incidence of
      ventricular ectopic beats, as well as to confirm that reducing the blood pressure
      by a diuretic may also reduce the ectopic frequency. Thirty-four ambulatory
      patients with ventricular ectopic beats and a systolic blood pressure of 131.33
      +/- 17.46 mmHg had a 24-hour Holter electrocardiographic and blood pressure
      monitoring following 1 week off any antiarrhythmic and antihypertensive
      treatment. Then they received for one week a standard diuretic combination
      (amiloride 5 mg + hydrochlorothiazide 50 mg) at a dose depending on their
      systolic pressure value and their monitoring was repeated. The mean hourly values
      of systolic blood pressure, heart rate and ventricular ectopic beats were
      "normalized", i.e. expressed as (x-x)/SD, taking each patient's 24-hour average
      as zero and his own standard deviation as the unit of measurement. As a group,
      there was an independent positive correlation between blood pressure and ectopic
      beats, while the heart rate was a nonsignificant negative factor for ectopic
      beats. On an individual level, however, an independent positive significant
      correlation between blood pressure and ectopic beats was found in only 8 cases,
      with a negative one in 4 cases. While the blood pressure of the group ranged
      symmetrically around its daily average value, the corresponding ectopic beat
      curve was highly asymmetric, with a very high incidence (up to 2.56 +/- 0.52 SD)
      for a rather short time (only 9.41 +/- 3.56 hours above average) and a low
      incidence (up to 1.26 +/- 0.49 SD) for the remaining 14.59 hours below average.
      Sudden rises in ectopic beat (greater than 1 SD/hour) occurred 1 to 6 times per
      day in each individual, significantly (P less than 0.01) more often (20.31%) with
      a high (greater than 1 SD) blood pressure than with a low (less than -1 SD) one
      (8.99%) with intermediate frequencies at intermediate pressures. After treatment
      with the diuretic, the systolic blood pressure was reduced, the heart rate
      increased and the ventricular ectopic beat incidence reduced (significant
      changes). The mean change in systolic pressure in 25 patients with a reduction in
      ectopy was a significant (P less than 0.01) decrease (-5.21 +/- 8.70 mmHg) while
      in the remaining 9 cases there was a non significant increase (+1.68 +/- 7.63
      mmHg). The heart rate was higher in both subgroups.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1372302
TI  - Absent left-sided atrioventricular connexion, with right atrium connected to left
      ventricle: prospective diagnosis in infancy, and outcome.
AB  - Prospective echocardiographic diagnosis of absence of the left atrioventricular
      connexion, with the right atrium connected to a morphologic left ventricle
      through a bileaflet morphologically mitral valve, was made in six infants. The
      rudimentary right ventricle was left-sided in all patients, and separated from
      the left atrium by sulcus tissue. The ventriculoarterial connexions were
      discordant. Associated defects included subpulmonary stenosis (2 patients),
      pulmonary atresia (1 patient), and a patent duct (4 patients). All patients
      developed early left atrial hypertension due to a restrictive interatrial septum,
      and required transcatheter septostomy (5 patients), or surgical septectomy (3
      patients). One patient who had a severely restrictive ventricular septal defect
      died following cardiac catheterization. In three others the ventricular septal
      defect has become progressively restrictive on serial catheterization. Successful
      intermediate term palliation has been performed in two patients using a
      bidirectional Glenn anastomosis, together with enlargement of the ventricular
      septal defect and a Damus-Kay-Stansel procedure in one. It is possible to
      distinguish this malformation from "mitral atresia" using cross-sectional
      echocardiography. The long-term outlook is influenced by early relief of left
      atrial hypertension. Balloon atrial septostomy alone is usually inadequate, and
      either blade septostomy or surgical septectomy are required. Serial cardiac
      catheterization is mandatory for planning definitive palliation.

PMID- 1372303
TI  - HLA class II variation in the Gila River Indian Community of Arizona: alleles,
      haplotypes, and a high frequency epitope at the HLA-DR locus.
AB  - A genetic distribution for the HLA class II loci is described for 349 "full
      blooded" Pima and Tohono O'odham Indians (Pimans) in the Gila River Indian
      Community. A high frequency epitope in the *DRw52 family was defined by reactions
      with 31 alloantisera, which we have designated *DR3X6. It segregates as a
      codominant allele at HLA-DR with alleles *DR2, *DR4, and *DRw8, and has the
      highest frequency yet reported for an HLA-DR specificity, 0.735. It forms a
      common haplotype with *DRw52 and *DQw3 that is a valuable marker for genetic
      admixture and anthropological studies. Phenotype and allele frequencies, and
      haplotype frequencies for two and three loci, are presented. Variation at these
      loci is highly restricted, the mean heterozygosity for HLA-DR and HLA-DQ being
      0.361. The Pimans represent a contemporary model for the Paleo-Indians who first
      entered North America 20,000 to 40,000 years ago.

PMID- 1372304
TI  - Identification of residues involved in polymorphic antibody binding epitopes on
      HLA-DR molecules.
AB  - Based on previous studies it was predicted that amino acids 4 or 25 of the DR4
      beta 1 and DR7 beta 1 chains are involved in polymorphic antibody binding
      epitopes on DR4 or DR7 molecules. These predictions were tested by analyzing
      monoclonal antibody (mAb) binding to transfectants expressing mutant DR4 beta 1
      or DR7 beta 1 chains with single amino acid substitutions at positions 4 or 25.
      Antibody binding to transfectants expressing additional DR4/7 beta 1 hybrids was
      also analyzed to assess further the contributions of four segments of the DR4
      beta 1 or DR7 beta 1 chains: amino acids 1-20, 21-40, 41-97, and the beta 2
      domain. Single amino acid substitutions at positions 4 and 25 of the DR4 beta 1
      chain or DR7 beta 1 chain eliminate binding of several mAb to DR4 or DR7
      molecules, documenting that these residues are involved in antibody epitopes.
      However, the data with the hybrid DR4/7 beta 1 chains indicate that some of these
      epitopes require contributions from both segments 1-20 and 21-40 of these DR beta
      chains, whereas other epitopes can be generated by placing the appropriate
      segment in the context of the other DR beta chain. In addition, the data with
      other mAb indicate that their epitopes are determined primarily by sequences
      within the 41-97 segment or in the beta 2 domain.

PMID- 1372305
TI  - The dream in terminal illness: a Jungian formulation.
AB  - It is a central assumption of Jungian theory that psychical transformation
      occurring during the critical developmental stages of the life cycle is
      anticipated, inspired, and orchestrated by the archetypal symbol. In this way,
      archetypal dreams are afforded particular significance during these transitional
      stages. The present paper purports to consider the clinical and theoretical
      implications of this understanding with reference to the dying process. The
      concepts discussed are illustrated by a series of dreams of a terminally ill
      cancer patient, which are elucidated by way of the method of amplification.
      Thematic analysis of the dream series supports Jung's conceptualization of death
      and dying as being a critical stage of the individuation process, characterized
      by profound psychical development of a specific and purposeful nature. The value
      of using dreams in the psychotherapeutic care of dying patients and their
      families is discussed, with case illustrations. It is suggested that such an
      approach may foster creative development, assist patients to integrate
      meaningfully subjective experiences pertaining to dying, and counteract the sense
      of isolation experienced by the terminally ill. The need for further research and
      the development of specific treatment modalities is highlighted.

PMID- 1372307
TI  - Microbial transformation of immunosuppressive compounds. I. Desmethylation of
      FK506 and immunomycin (FR 900520) by Actinoplanes sp. ATCC 53771.
AB  - The immunosuppressants FK506 and FR 900520 were desmethylated by Actinoplanes sp.
      ATCC 53771 to yield various O-desmethylated products. The products were isolated
      and purified by solvent extraction and HPLC chromatography, and identified by NMR
      and MS spectroscopy.

PMID- 1372306
TI  - Sperabillins, new antibacterial antibiotics with potent in vivo activity.
      Taxonomy, fermentation, isolation and biological activity.
AB  - A Gram-negative bacterium was found to produce new antibacterial antibiotics,
      sperabillins A, B, C and D, and the producing bacterium was characterized and
      identified as Pseudomonas fluorescens YK-437. Sperabillins were isolated by
      column chromatographies using cation-exchange resins, activated carbon and cation
      exchange Sephadex, and preparative reverse-phase HPLC. Sperabillins showed
      antibacterial activity against Gram-negative and Gram-positive bacteria including
      antibiotic-resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus.
      Sperabillin A inhibited DNA, RNA, protein, and cell wall biosynthesis in
      Escherichia coli. Sperabillins showed good protective effects in experimentally
      infected mice.

PMID- 1372308
TI  - Identity of immunosuppressant FR-900520 with ascomycin.

PMID- 1372309
TI  - Protactin, a new antibiotic metabolite and a possible precursor of the
      actinomycins.
AB  - Streptomyces cucumerosporus strain L703-4 (ATCC 53784) produces a new 4-methyl-3
      hydroxyanthraniloylpentapeptide lactone for which we have proposed the name
      protactin, in addition to several actinomycin components. Protactin is rather
      resistant to air oxidation but it can be converted to a new actinomycin,
      actinomycin Zp by ferricyanide oxidation. Actinomycin Zp possesses in vitro
      antibacterial activity and in vivo antitumor activity against P-388 leukemia in
      mice.

PMID- 1372310
TI  - Antibiotics from basidiomycetes. XLI. Clavicoronic acid, a novel inhibitor of
      reverse transcriptases from Clavicorona pyxidata (Pers. ex Fr.) Doty.
AB  - A novel inhibitor of RNA-directed DNA-polymerases was isolated from fermentations
      of Clavicorona pyxidata. Its structure was elucidated by spectroscopic methods.
      Clavicoronic acid (1) is a noncompetitive inhibitor of avian myeloblastosis virus
      (Ki 130 microM) and Moloney murine leukemia virus (Ki 68 microM) reverse
      transcriptases. In permeabilized cells and isolated nucleic DNA- and RNA
      synthesis are not affected. Clavicoronic acid markedly inhibits the
      multiplication of vesicular stomatitis virus in baby hamster kidney cells by
      interfering with this virus's RNA-directed RNA-polymerase. 1 exhibits no
      cytotoxic and very weak antimicrobial activities.

PMID- 1372311
TI  - Expression of an early gene in the flagellar regulatory hierarchy is sensitive to
      an interruption in DNA replication.
AB  - Genes involved in the biogenesis of the flagellum in Caulobacter crescentus are
      expressed in a temporal order and are controlled by a trans-acting regulatory
      hierarchy. Strains with mutations in one of these genes, flaS, cannot transcribe
      flagellar structural genes and divide abnormally. This gene was cloned, and it
      was found that its transcription is initiated early in the cell cycle. Subclones
      that restored motility to FlaS mutants also restored normal cell division.
      Although transcription of flaS was not dependent on any other known gene in the
      flagellar hierarchy, it was autoregulated and subject to mild negative control by
      other genes at the same level of the hierarchy. An additional level of control
      was revealed when it was found that an interruption of DNA replication caused the
      inhibition of flaS transcription. The flaS transcript initiation site was
      identified, and an apparently unique promoter sequence was found to be highly
      conserved among the genes at the same level of the hierarchy. The flagellar genes
      with this conserved 5' region all initiate transcription early in the cell cycle
      and are all sensitive to a disruption in DNA replication. Mutations in these
      genes also cause an aberrant cell division phenotype. Therefore, flagellar genes
      at or near the top of the hierarchy may be controlled, in part, by a unique
      transcription factor and may be responsive to the same DNA replication cues that
      mediate other cell cycle events, such as cell division.

PMID- 1372312
TI  - Premature termination of in vivo transcription of a gene encoding a branched
      chain amino acid transport protein in Escherichia coli.
AB  - Previous studies have suggested that control of expression of genes of the LIV-I
      permease system for the high-affinity transport of branched-chain amino acids in
      Escherichia coli involves modulation in the frequency of mRNA elongation.
      Mutation of the Rho transcription termination factor and shortages of charged
      leucyl-tRNA have been shown to alter LIV-I transport activity. Rho-dependent
      transcription termination regulated by shortages of charged leucyl-tRNA at sites
      preceding structural genes has been proposed to account for their role in
      regulation of LIV-I transport. Transcription of the livJ-binding protein gene,
      encoding one of the periplasmic components of the LIV-I system, was analyzed in
      vivo with strains which lack repression of the LIV-I genes and harbor a
      temperature-sensitive allele for either leucyl-tRNA synthetase or Rho factor.
      Analysis of mRNA synthesis by DNA-RNA hybridization in the various mutant strains
      indicated that both shortages of leucyl-tRNA caused by inactivation of the
      temperature-sensitive leucyl-tRNA synthetase and inactivation of the Rho factor
      were associated with increased synthesis of livJ mRNA. Nuclease protection and
      gel electrophoresis studies detected prematurely terminated transcripts
      corresponding in size to the leader region of livJ mRNA. Accumulations of these
      short transcripts were suppressed in strains harboring temperature-sensitive
      alleles for either leucyl-tRNA synthetase or Rho factor. These results provide
      support for the hypothesis that expression of livJ involves Rho-dependent
      transcription termination in which antitermination is associated with the
      intracellular availability of aminoacyl leucyl-tRNA.

PMID- 1372313
TI  - Expression of Erwinia amylovora hrp genes in response to environmental stimuli.
AB  - Seven hrp loci that are essential for the hypersensitive reaction elicited by
      Erwinia amylovora were transcriptionally fused with a derivative of transposon
      Tn5, containing the promoterless Escherichia coli beta-glucuronidase reporter
      gene. The seven hrp fusions were used to monitor expression of the hrp loci in
      vitro and in planta. No significant expression was detected in rich medium for
      any of the fusions. However, five of them were expressed highly in planta and in
      inducing medium that contains mannitol, salts, and 5 mM (NH4)2SO4. Expression of
      these five hrp loci is regulated by ammonium, nicotinic acid, complex-nitrogen
      sources, certain carbon sources, temperature, and pH. Under well-defined
      conditions, i.e., in inducing medium, no specific plant components were required
      for transcriptional activation of the hrp loci. The high levels of expression
      detected in vitro were comparable to those determined during the development of
      the hypersensitive reaction in tobacco. Differential levels of expression of the
      hrp loci occurred in host and nonhost plants. In pear, a host plant, expression
      of the hrp loci was delayed and greatly reduced compared with expression in
      tobacco leaves, a nonhost.

PMID- 1372314
TI  - Cloning, sequencing, and transcriptional regulation of the Vibrio cholerae fur
      gene.
AB  - Many genes involved in the transport of iron by bacteria as well as in
      pathogenesis are regulated by the environmental concentration of iron, with
      increased expression under low-iron conditions. In Escherichia coli,
      transcriptional regulation by iron depends on the fur gene. A virulence gene in
      Vibrio cholerae (irgA) is also transcriptionally regulated by iron, and the
      promoter of irgA contains a dyad repeat homologous to Fur binding sites in E.
      coli. Southern hybridization of V. cholerae chromosomal DNA, using an internal
      fragment of E. coli fur as a probe, showed a single hybridizing sequence under
      conditions of low stringency. We derived a restriction map in the vicinity of
      this hybridizing sequence; overlapping PstI and HindIII fragments were identified
      at the center of this map. The cloned PstI fragment failed to complement an E.
      coli fur mutant; sequence analysis revealed an open reading frame that began just
      downstream of the PstI site, suggesting that the clone was not functional because
      it lacked its promoter. The overlapping HindIII fragment contained the intact V.
      cholerae fur gene with its promoter and complemented an E. coli fur mutant. DNA
      sequencing of the HindIII fragment demonstrated a single open reading frame of
      150 amino acids that was 76% homologous to E. coli Fur. Primer extension analysis
      localized two promoters for the V. cholerae fur gene; no significant homology to
      an E. coli Fur binding site was identified for either promoter. Northern blot
      analysis showed that the two fur transcripts were not strongly regulated by iron.
      These studies identify a gene in V. cholerae homologous in both function and
      sequence to the fur gene of E. coli, and we have designated this gene the fur
      gene of V. cholerae.

PMID- 1372315
TI  - Immunochemical and structural analysis of the O polysaccharides of Salmonella
      zuerich [1,9,27,(46)].
AB  - Salmonella zuerich [1,9,27,(46)] has been shown to exhibit two levels of
      structural heterogeneity. The bacterium carries two distinct O-polysaccharide
      molecules with and without O:factor 1. Both sets of molecules (1+ and 1-) carry
      the two O:factors 27 and 46 on the same O chain, but they are expressed unevenly;
      in contrast to factor 27, O:factor 46 is always weakly expressed. Part of this
      weak expression was thought to be due to strong inhibition of factor 46 by factor
      1. In this study, serological analysis gave more detailed information on the
      sizes of the different O:factor epitopes. Structural analysis of S. zuerich O
      polysaccharides showed that they are constructed of the expected chemical
      sequences characteristic of factors 1, 9, 27, and 46. No modification in the
      sugar sequence could account for the weak expression of O:factor 46. Factors 27
      and 46 are present on oligosaccharides carrying either an alpha-Man (factor 27)
      or a beta-Man (factor 46) residue. In S. zuerich, the alpha-Man configuration is
      predominant, corroborating the expression of strong factor 27 and weak factor 46
      on the bacteria. Questions raised by the existence of such heterogeneous O
      polysaccharides on the specificity of the O chain polymerase, as well as the
      place of S. zuerich in Salmonella evolution, are dicussed in this paper.

PMID- 1372316
TI  - Construction of Salmonella strains with both antigen O4 (of group B) and antigen
      O9 (of group D).
AB  - A Salmonella live vaccine causing both O4- and O9-specific immune responses would
      be of use, but no reported Salmonella serotype has both of these O antigens.
      Constructed Salmonella typhimurium strains with an rfb (O-antigen-specifying)
      gene cluster of type D in the chromosome and one of type B in an F'-rfb+ factor,
      and those with the reverse combination reacted strongly with both anti-O4 (and
      anti-O5) and anti-O9 sera and, if they carried recA, could be maintained in this
      state by growth conditions selective for retention of the F' factor. One of the
      two B.rfb+ gene clusters of a (P22-lysogenic) S. typhimurium strain with a tandem
      duplication of a chromosomal segment including hisD and B.rfb+ was replaced (by
      transduction) by a D.rfb+ gene cluster; the resulting strain was O1+ O4+ O5+ O9+
      and stable as such after being made recA. A stable O4+ O9+ derivative of a
      virulent S. enteritidis (O-group D) strain was made by transducing into it first
      the join point of an appropriate tandem duplication strain, together with the
      adjacent B.rfb+ gene cluster, and then srl::Tn10 recA.

PMID- 1372317
TI  - Structural and immunochemical studies of the lipopolysaccharides of Salmonella
      strains with both antigen O4 and antigen O9.
AB  - Two Salmonella hybrid strains, SL5313 (Salmonella typhimurium with a D.rfb+ gene
      cluster) and SL5396 (S. enteritidis with a B.rfb+ gene cluster), each expressing
      both O-antigen 4 (of serogroup B) and O-antigen 9 (of serogroup D) were studied
      by immunofluorescence using a mixture of O4-specific mouse monoclonal and O9
      specific rabbit polyclonal antibodies. Bound antibodies, detected by anti-mouse
      antibody labelled with fluorescein isothiocyanate and anti-rabbit antibody
      labelled with tetramethylrhodamine isothiocyanate showed that more than 98% of
      the bacteria expressed both the O4 and O9 epitopes. Phenol-water-extracted
      lipopolysaccharide from batch-grown cultures subjected to sugar and methylation
      analyses by gas-liquid chromatography and mass spectrometry were shown to contain
      abequose (of the O4 epitope) and tyvelose (of the O9 epitope) in ratios of 1:1.5
      and 1:2.5 for SL5313 and SL5396, respectively. Isolated polysaccharide chains,
      obtained by weak-acid hydrolysis of the lipopolysaccharides, were found to
      contain both O4 and O9 specificities in the same molecule, since polysaccharide
      bound to O4 antibody attached to a solid-phase-adsorbed O9-specific antibody and
      vice versa. This demonstrates that in strains SL5313 and SL5396 O chains
      containing both O4 repeating units (from S. typhimurium) and O9 units (from S.
      enteritidis) are present.

PMID- 1372318
TI  - Effects of analogs of 1,25(OH)2 vitamin D3 on the proliferation and
      differentiation of the human chronic myelogenous leukemia cell line, RWLeu-4.
AB  - We evaluated the proliferative and differentiative effects of analogs of
      1,25(OH)2 vitamin D3 [1,25(OH)2D3] on a chronic myelogenous leukemia cell line,
      RWLeu-4, which is growth-inhibited and differentiates in response to 1,25(OH)2D3
      (ED50 = 3-10 nM). Side-chain-fluorinated analogs were more potent (ED50 = 0.7-2
      nM) while most of those with altered saturation of the D ring or side-chain
      carbon-carbon bonds were equally or less effective than 1,25(OH)2D3. However, the
      two analogs with either two additional double bonds or an extra double and triple
      bond in the D ring had greater antiproliferative activity [1,25(OH)2-16,23-diene
      D3 (ED50 = 2.7 nM) and 1,25(OH)2-16-ene-23-yne D3 (ED50 = 0.7 nM)]. Since the
      latter of these has been reported to be less potent at mobilizing calcium than
      1,25(OH)2D3, it (or a similar compound) may be a candidate for clinical use as an
      antineoplastic agent.

PMID- 1372319
TI  - Membrane transport in multidrug resistance, development, and disease. AACR
      special conference in cancer research.
AB  - The main goal of this meeting was to provide the scientists and clinicians active
      in this field with a comprehensive overview of the progress that has been made.
      The meeting was a forum in which new advances in membrane transport were
      discussed in depth and which gave new impulses for clinical applied research.
      Again, the importance of intensive cooperation between basic research and
      clinical use became evident during this symposium.

PMID- 1372320
TI  - Hausdorff dimension as a quantification of local roughness of protein surfaces.
AB  - Based on structural information from the Brookhaven Protein Data Bank, the
      contact surfaces of the proteins lysozyme, trypsin, and BPTI (bovine pancreatic
      trypsin inhibitor) with a spherical test particle of the size of a water molecule
      have been calculated and systematically analyzed. It is our purpose to establish
      (i) self-similarity as a statistical concept for the characterization of surface
      roughness and (ii) the Hausdorff dimension as a measure of the local surface
      complexity. It is found that the proteins statistically show self-similarity
      within a yardstick range 1.2 A less than R less than 20 A, and that this concept
      also holds reasonably for parts of the surface which are not too small.

PMID- 1372321
TI  - Expression of serum insulin-like growth factors, insulin-like growth factor
      binding proteins, and the growth hormone-binding protein in heterozygote
      relatives of Ecuadorian growth hormone receptor deficient patients.
AB  - Recently, an isolated population of apparent GH-receptor deficient (GHRD)
      patients has been identified in the Loja province of southern Ecuador. These
      individuals presented many of the physical and biochemical phenotypes
      characteristic of Laron-Syndrome and are believed to have a defect in the GH
      receptor gene. In this study, we have compared the biochemical phenotypes between
      the affected individuals and their parents, considered to be obligate
      heterozygotes for the disorder. Serum GH, insulin-like growth factor I and II
      (IGF-I and IGF-II) levels were measured by RIA Insulin-like growth factor binding
      proteins. (IGFBPs) were measured by Western ligand blotting (WLB) of serum
      samples, following separation by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, and relative quantitation of serum IGFBPs was performed with a
      scanning laser densitometer. Serum GH-binding protein (GHBP) levels were measured
      with a ligand-mediated immunofunctional assay using a monoclonal antibody raised
      against the GHBP. These values were then compared to values obtained from normal,
      sex-matched adult Ecuadorian controls, to determine if the above parameters were
      abnormal in the heterozygotes. The serum IGF-I levels of the GHRD patients were
      less than 13% of control values for adults and 2% for children. However, the IGF
      I levels of both the mothers and fathers were not significantly different from
      that of the control population. The serum IGF-II levels of the GHRD patients were
      approximately 20% of control values for adults and 12% for the children. The IGF
      II levels of the mothers were reduced, but were not significantly different from
      that of the control population. However, IGF-II levels of the fathers were
      significantly lower than those of controls (64% of control male levels). WLB
      analysis of serum IGFBP levels of the affected subjects demonstrated increased
      IGFBP-2 and decreased IGFBP-3, suggesting an inverse relationship between these
      IGFBPs. The GHRD patients who had the lowest serum IGFBP-3 levels (as measured by
      WLB) demonstrated a serum protease activity that could proteolyze 125I-IGFBP-3.
      GHRD patients who had higher serum IGFBP-3 levels lacked this serum protease
      activity. There were no differences in the serum IGFBP profiles of the mothers or
      the fathers for either IGFBP-2 or IGFBP-3, and serum from both groups lacked the
      ability to significantly proteolyze 125I-IGFBP-3. While GHRD patients had very
      low levels of serum GHBP, some patients did have measurable GHBP levels.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1372323
TI  - Characterization of urinary insulin-like growth factor binding proteins.
AB  - The insulin-like growth factors (IGFs) are important mitogens that are present in
      many body fluids, where they are commonly bound with high affinity to IGF binding
      proteins (IGFBPs). We investigated human urine for the presence of IGFBPs.
      Western ligand blots of concentrated, dialyzed normal urine disclosed the
      presence of two major bands with IGF binding activity, one at 40-44 kilodaltons
      and another at 31 kDa. Deglycosylation with endoglycosidase F, and
      immunoprecipitation with alpha HEC1 antibody revealed these proteins to be hIGFBP
      3 and hIGFBP-2, respectively. Comparison of IGFBPs in normal serum and urine
      showed a reversal of the hIGFBP-2/hIGFBP-3 ratio in urine compared to serum, with
      hIGFBP-2 being the predominant binding protein in normal urine. The 150 kDa form
      of hIGFBP-3 was absent in normal urine. In patients with renal disease, the
      urinary IGFBP (U-IGFBP) pattern was altered. Patients with glomerular disease and
      proteinuria had elevated U-hIGFBP-3, whereas patients with renal failure who
      displayed increased urinary beta-2-microglobulin had a dramatic increase in U
      hIGFBP-1, in the face of normal serum IGFBP profiles. In conclusion, we have
      documented the presence of IGFBPs in the urine of normal and diseased
      individuals. The presence of IGFBPs in urine may complicate the assessment of IGF
      measurements in urine. U-IGFBPs may be potential clinical markers in renal
      diseases. Additional studies are required before the origin of urinary IGFBPs in
      both normal and pathological conditions will be definitively established.

PMID- 1372322
TI  - Insulin-like growth factor binding protein profiles in human ovarian follicular
      fluid correlate with follicular functional status.
AB  - The insulin-like growth factors (IGF), IGF-I and IGF-II, influence ovarian
      follicular development. The IGF binding proteins (IGFBPs) comprise at least six
      distinct species which may modulate IGF action. We examined IGFBP profiles in
      follicular fluid (FF) from developing human ovarian follicles with aromatase
      activity as well as from androgen-dominant, atretic follicles. Western ligand
      blot analysis of FF from both atretic and active follicles revealed the presence
      of IGFBP-3 and IGFBP-2, confirmed by immunoprecipitation with specific antiserum,
      as well as 28 kilodalton (kDa) and 24 kDa IGFBPs. In FF specimens obtained during
      the follicular phase, IGFBP-2 and the 28 kDa and 24 kDa species were present in 3
      , 6-, and 19-fold higher amounts in atretic compared to healthy developing
      follicles, respectively, and were present in greater amounts in atretic FF than
      in serum. In atretic FF obtained during the luteal phase, lower levels of IGFBP-2
      and the 28 and 24 kDa IGFBPs were seen than in atretic follicles in the
      follicular phase. IGFBP-3 levels were comparable in all types of follicles and in
      serum. The 28 kDa IGFBP is glycosylated, and its level varied in parallel with
      the 24 kDa IGFBP, suggesting that these are variants of the recently identified
      IGFBP-4. IGFBP-1 was not detectable by immunoprecipitation and ligand blotting of
      FF obtained during the follicular phase. These data suggest that one or more
      IGFBPs present in higher levels in FF from atretic compared to healthy,
      developing follicles may play an important role in folliculogenesis and
      follicular atresia.

PMID- 1372324
TI  - Myasthenia gravis patients with a thymoma have antibodies against a high
      molecular weight protein in sarcoplasmic reticulum.
AB  - Our purpose was to investigate whether components of the sarcoplasmic reticulum
      (SR) are relevant antigens in myasthenia gravis (MG). Using enzyme-linked
      immunosorbent assay (ELISA), 75 MG sera and 120 control sera were examined for
      IgG antibodies against SR prepared from rabbit skeletal muscle. 16/30 thymoma MG
      patients had IgG antibodies that reacted with SR. 1/30 MG patients with thymic
      hyperplasia and 3/15 MG patients with thymic atrophy had SR antibodies in low
      concentrations. Control sera were negative. Using immunoblot, SR antibodies were
      detected in the thymoma group only. 14/30 sera from thymoma patients reacted with
      a protein of 320 kDa relative molecular weight. The only reported SR protein with
      similar electrophoretic mobility is the subunit of the spanning protein which
      links junctional SR to sarcolemma and functions as a calcium-release channel.

PMID- 1372325
TI  - Studies of V beta 8 T cell receptor peptide treatment in experimental autoimmune
      encephalomyelitis.
AB  - Lewis rats immunized with T cell receptor (TCR) variable region peptide V beta 8
      in complete Freund's adjuvant (CFA) were protected against experimental
      autoimmune encephalomyelitis (EAE) induced with myelin basic protein in CFA,
      although variable protection was also observed in rats injected with control
      peptide in CFA, or CFA alone. However, this adjuvant-mediated protection could be
      avoided by immunizing with TCR peptide in incomplete adjuvant (IFA). Clinical,
      but not histologic EAE was suppressed in rats given V beta 8 peptide in IFA,
      whereas control animals injected with V beta 14 peptide in IFA, or IFA alone
      developed severe clinical EAE. Anti-V beta 8 antibodies were present in the sera
      of all V beta 8-treated rats. These findings lend support to the hypothesis that
      autoimmune disease can be suppressed by inducing an immune response against the
      TCR-idiotope of autoreactive T cells.

PMID- 1372326
TI  - IgG anti-ganglioside antibodies and their subclass distribution in two patients
      with acute and chronic motor neuropathy.
AB  - IgG anti-ganglioside antibodies were found in two patients with motor neuropathy.
      The first patient had a chronic axonal neuropathy with persistently elevated anti
      GM1 antibodies. The second patient had an acute axonal neuropathy with anti-GM1,
      GD1b and asialoGM1 antibodies. In both, the IgG subclass study showed that the
      antibodies belonged to the IgG1 subclass. An enzyme-linked immunosorbent assay
      (ELISA) for light chains revealed anti-ganglioside antibodies of the lambda type.

PMID- 1372327
TI  - T cells in the spinal cord in experimental autoimmune encephalomyelitis are
      matrix adherent and secrete tumor necrosis factor alpha.
AB  - We examined T cells isolated from an autoimmune tissue lesion and from lymphoid
      organs for their ability to secrete tumor necrosis factor-alpha (TNF-alpha) and
      to adhere to extracellular matrix (ECM) proteins. CD4+ T cells were obtained from
      spleens, popliteal lymph nodes, and spinal cords of Lewis rats that had been
      immunized with myelin basic protein (MBP) to induce experimental autoimmune
      encephalomyelitis (EAE). We now report that, irrespective of whether or not the T
      cells were activated with MBP or the T cell mitogen concanavalin A (ConA), the T
      cells isolated from the spinal cord lesions secreted greater amounts of TNF-alpha
      and adhered better to ECM than did T cells from the draining lymph node. Thus,
      the lesions of EAE concentrate a subpopulation of CD4+ T cells with enhanced
      ability to interact with blood vessel wall components and to secrete TNF-alpha.

PMID- 1372328
TI  - Microglial and astroglial reactions to inflammatory lesions of experimental
      autoimmune encephalomyelitis in the rat central nervous system.
AB  - Gliosis is a repair process of lesions appearing in the central nervous system
      (CNS). Although gliosis by astrocytes (astrocytic gliosis) has been well
      documented, that by microglia (microglial gliosis) remains poorly understood. In
      the present study we induced experimental autoimmune encephalomyelitis (EAE) in
      Lewis rats and examined microglial and astroglial reactions to EAE lesions at
      various stages of the disease by immunohistochemistry. For the demonstration of
      microglia and astrocytes, antibodies against complement receptor type 3 (OX42)
      and glial fibrillary acidic protein (GFAP) were used, respectively. It was
      revealed that the whole course of microglial and astroglial reactions to EAE
      lesions is divisible into three stages, i.e., initial, peak and recovery stages.
      Microglial and astroglial reactions to EAE lesions at each stage correspond well
      with the clinical and histological stages of EAE. At the initial stage, rats
      showed mild clinical signs and a few inflammatory foci were found in the CNS.
      Microglia were increased in number in close association with inflammatory cell
      aggregates, whereas astrocytes showed no significant reaction in spite of the
      presence of inflammatory cells. At the peak stage, rats showed full-blown EAE and
      the number of inflammatory cells reached maximum. The most characteristic finding
      at this stage was 'encasement' of inflammatory lesions by astrocytic fibers.
      Microglia were increased in number, but association of microglia with lesions was
      prevented by astrocytes. Interestingly, however, such characteristic distribution
      of microglia and astrocytes was not observed at the recovery stage. Residual
      inflammatory cell aggregates were intermingled with dense microglial and
      astrocytic gliosis, forming 'micro-astroglial scars'. Double immunofluorescence
      staining with anti-GFAP and anti-bromodeoxyuridine (BrdU), or with OX42 and anti
      BrdU revealed that BrdU-incorporated microglia, but not astrocytes, were present
      mainly at the initial and peak stages, suggesting that microglia would
      proliferate by cell division to create gliosis, whereas astrocytic gliosis would
      be a result of migration of astrocytes and/or up-regulation of expression of GFAP
      molecule. Taken together with previous in vitro findings that microglia, but not
      astrocytes, stimulate encephalitogenic T cell proliferation, these in vivo
      findings suggest that microglia augment, whereas astrocytes suppress,
      inflammatory processes in the CNS.

PMID- 1372329
TI  - Increase of peripheral B lymphocytes committed to the production of monoreactive
      and high affinity antibodies to HTLV-1 in patients with HAM/TSP.
AB  - We quantitated the frequency of B lymphocytes capable of producing antibodies to
      HTLV-1 in the peripheral blood from patients with HAM/TSP, non-HAM/TSP HTLV-1
      carriers and seronegative healthy subjects. Epstein-Barr virus (EBV) was used as
      a polyclonal activator of B lymphocytes in a limiting dilution condition. We
      found that B lymphocytes committed to the production of monoreactive-IgG and -IgA
      antibodies to recombinant HTLV-1 (gag + env) hybrid protein were significantly
      increased in a number in patients with HAM/TSP as compared to non-HAM/TSP HTLV-1
      carriers and seronegative healthy subjects. By transforming these B lymphocytes
      with EBV and fusing them with human-mouse heteromyeloma (F3B6), a stable
      hybridoma producing IgG monoclonal antibody (mAb) to HTLV-1 (gag + env) protein
      was generated from a patient with HAM/TSP. This mAb (IgG1, kappa), designated
      F31.1, specifically bound to the amino acid residues from 235 to 254 of HTLV-1
      envelope glycoproteins (gp46) with high affinity (Kd = 4.0 x 10(-9) mol/l). These
      data indicate that the antigen-driven process of B lymphocytes maturation by HTLV
      1 antigens is markedly increased in patients with HAM/TSP.

PMID- 1372330
TI  - Continuous in vivo treatment with catecholamines suppresses in vitro reactivity
      of rat peripheral blood T-lymphocytes via alpha-mediated mechanisms.
AB  - A 20 h continuous treatment of rats with catecholamines, using subcutaneously
      implantable retard tablets, had either no (adrenaline, isoproterenol, midodrine)
      or a slight (noradrenaline) suppressive effect on the in vitro responsiveness of
      peripheral blood T-lymphocytes. A marked suppression of the mitogen response
      ensued when adrenaline, noradrenaline or midodrine, but not isoproterenol, was
      applied together with the beta-receptor blocker propranolol, whereas the
      combination with the alpha-receptor blocker phentolamine had no effect. The
      mitogen response of splenic lymphocytes was not affected by any of these
      treatments. This alpha-mediated adrenergic suppression of peripheral blood T
      cells was not correlated with general metabolic alterations, shifts in white
      blood cell counts or CD4+/CD8+ subsets, or with elevated glucocorticoid levels.
      The data suggest that to consistently influence the reactivity of rat peripheral
      blood lymphocytes by chronic adrenergic stimuli in vivo requires both high
      catecholamine levels and a bias towards alpha-adrenergic receptivity.

PMID- 1372331
TI  - Immunoregulatory effects of neuropeptides. Stimulation of interleukin-2
      production by substance p.
AB  - Substance P (SP), a tachykinin neuropeptide, has been previously reported to
      stimulate T cell proliferation, and SP receptors have been identified on
      subpopulations of T lymphocytes. The effect of SP on the interleukin-2 (IL-2)
      production has been investigated by using the murine EL-4.IL-2 and LBRM-T6G T
      cell lines. SP synergized with phorbol 12-myristate 13-acetate (PMA) in a dose
      dependent manner to induce IL-2 production. The generated interleukin was
      identified as IL-2 by neutralization with a specific anti-murine IL-2 monoclonal
      antibody. The effect of SP was specific, since spantide and physalaemin which
      have affinity for SP receptors inhibited the generation of IL-2 by SP. These
      results provide additional evidence for the immunoregulatory role of
      neuropeptides, and suggest that the immunostimulatory action of SP could be
      mediated, at least in part, through the upregulation of IL-2 expression.

PMID- 1372332
TI  - Copolymer-1-induced inhibition of antigen-specific T cell activation:
      interference with antigen presentation.
AB  - Copolymer-1 (Cop-1) has been shown to inhibit in vivo development of experimental
      allergic encephalomyelitis (EAE) in animals and has been reported to have some
      therapeutic benefit in relapsing/remitting multiple sclerosis (MS). The mechanism
      by which Cop-1 acts in vivo is not known. The present study demonstrates that Cop
      1 inhibits the in vitro response of several antigen-specific murine T cell
      hybridomas restricted to I-A, and to a lesser extent, I-E. The ability of human
      myelin basic protein (MBP)-specific T cell lines (TCL) to lyse targets in the
      context of three HLA-DR types associated with MS was also impaired by Cop-1. The
      results suggest that the observed inhibition was due to competition between Cop-1
      and nominal antigen for the class II major histocompatibility complex (MHC)
      peptide binding site.

PMID- 1372333
TI  - Anti-MAG IgM paraproteins from some patients with polyneuropathy associated with
      IgM paraproteinemia also react with sulfatide.
AB  - Sera from five of 11 patients with neuropathy associated with IgM paraproteinemia
      (NAIgMPP) and reactivity against myelin-associated glycoprotein (MAG) also had
      elevated levels of IgM against sulfatide. Although three patients had anti
      sulfatide IgM titers of less than or equal to 1:1000, two patients had titers of
      greater than or equal to 1:50,000. Absorption of patient serum with sulfatide
      revealed that anti-MAG IgM paraproteins in two patients with high titer anti
      sulfatide IgM crossreacted with sulfatide. Our study is the first to show that
      some anti-MAG IgM paraproteins crossreact with sulfatide, a major acidic
      glycolipid of myelin. Moreover, some patients with NAIgMPP have polyclonal anti
      sulfatide IgM in addition to anti-MAG IgM paraproteins. Therefore, sulfatide may
      be a target antigen in some patients with NAIgMPP.

PMID- 1372334
TI  - Monoclonal antibody binding to peptide epitopes conjugated to synthetic branched
      chain polypeptide carriers. Influence of the carrier upon antibody recognition.
AB  - The peptide C A P D T R P A P G has been linked covalently to defined branched
      polypeptides with a polylysine backbone and side chains of DL-alanine or D
      leucine-DL-alanine oligopeptides. The peptide was coupled via its N terminal
      cysteine to the side chains of the macromolecular carrier to ensure uniform
      orientation. The compounds were subjected to compositional analyses to
      characterise the degrees of substitution and secondary structural studies were
      performed using circular dichroism spectroscopy. The peptide selected for
      investigation contains the immunodominant sequence P D T R P A P which is
      expressed in the protein core of epithelial mucins. It is to this region that
      many anti-mucin monoclonal antibodies bind (Burchell et al., 1989; Price et al.,
      1990a,b). With these characterised constructs, it has been possible to evaluate
      the influence of secondary structure upon the binding of monoclonal antibodies
      which recognise short linear sequences in the synthetic antigenic peptide. The
      findings are relevant to the design and construction of synthetic immunogens and
      vaccines as well as to the production of synthetic analogues of clinically
      relevant antigens (in this case, epithelial mucins associated with breast and
      ovarian carcinomas).

PMID- 1372335
TI  - Quantitative western blot analysis and spot immunodetection using time-resolved
      fluorometry.
AB  - We describe a new method of staining and quantification of proteins blotted or
      spotted on nitrocellulose. Blotted or spotted proteins are first reacted with
      specific antibodies followed by reaction with biotinylated secondary antibodies.
      The immunocomplex is then reacted with a streptavidin-based macromolecular
      complex labeled with the fluorescent europium chelate of 4,7
      bis(chlorosulfophenyl) 1,10-phenanthroline-2,9-dicarboxylic acid (BCPDA). The
      fluorescent spots or bands can then be assessed by visual inspection under UV
      illumination, by instant photography or quantified by scanning with a time
      resolved fluorometer. The method does not involve enzyme detection, is simple,
      sensitive and gives sharp bands which remain fluorescent for long periods of time
      (months to years).

PMID- 1372337
TI  - Amplification of viral RNA for the detection of dengue types 1 and 2 virus.
AB  - In vitro DNA amplification by means of the polymerase chain reaction (PCR) was
      used to amplify dengue types 1 and 2 viral genomes in cultured cells and in the
      serum of persons infected with dengue virus. Results of the present investigation
      suggest that the PCR method is type-specific in detecting dengue virus and has a
      detection sensitivity of less than 100 plaque-forming units (pfu) for both
      serotypes of the virus. The PCR method may be useful for detecting and typing
      dengue virus in clinical and epidemiological specimens.

PMID- 1372336
TI  - A novel solid-phase test to study the binding of IFN-gamma to its receptor.
AB  - A novel solid phase assay for interferon-gamma (IFN-gamma) binding to the human
      IFN-gamma receptor was developed. The receptor binding assay is carried out using
      a soluble form of the recombinant IFN-gamma receptor protein corresponding to the
      extracellular portion of the IFN-gamma receptor. Using different IFN molecules
      and anti-IFN monoclonal antibodies, we show that the specificity of the soluble
      IFN-gamma receptor coated to the plastic surface is not altered. In consequence,
      this new generation binding test can be used to characterize the interactions
      with the specific ligand under controlled conditions. In comparison with ELISA or
      RIA tests using antibodies specific for IFN-gamma, the solid-phase binding assay
      has the advantage of detecting only the active molecules. Finally, since the test
      has a large capacity, it is being applied for the screening of agents that are
      able to neutralize the IFN-gamma activity either by blocking the active site of
      the lymphokine or the binding site of the specific receptor.

PMID- 1372338
TI  - Degradation of fibronectin and vitronectin in chronic wound fluid: analysis by
      cell blotting, immunoblotting, and cell adhesion assays.
AB  - We used a combination of cell blotting, immunoblotting, and cell adhesion assays
      to analyze fibronectin and vitronectin in wound fluid from acute and chronic
      wounds. Acute wound fluid (e.g., suction blister fluid, mastectomy fluid)
      contained intact fibronectin and vitronectin as major cell adhesion proteins. In
      marked contrast, chronic wound fluid samples from three of 11 patients with
      venous stasis ulcers showed complete degradation of vitronectin and degradation
      of fibronectin into small molecular mass polypeptides less than 125 kDa. Three of
      these polypeptides--54, 93, and 125 kDa--were biologically active in promoting
      cell attachment and were recognized by monoclonal antibodies that bind
      fibronectin near the arg-gly-asp (RGD) domain. In wound fluid samples from the
      other eight of 11 patients, only slight degradation of vitronectin and
      fibronectin occurred, which resulted in a mixture of mostly intact molecules
      along with large fragments. Intact fibronectin in chronic wound fluid samples
      contained the ED-A domain, which showed that fibronectin synthesis occurred
      locally in the wound bed. Wound fluid containing extensively degraded vitronectin
      and fibronectin reversibly inhibited cell adhesion, and excess fetal bovine
      serum, but not purified fibronectin, neutralized the inhibitory effect. We
      suggest that protease activity in some chronic wounds may cause degradation of
      adhesion proteins and prevent cell adhesion necessary for normal wound closure.

PMID- 1372339
TI  - Substance P is diminished and vasoactive intestinal peptide is augmented in
      psoriatic lesions and these peptides exert disparate effects on the proliferation
      of cultured human keratinocytes.
AB  - An involvement of neurogenic components in the pathogenesis of psoriatic lesions
      has been suggested and neuropeptides are thought to play a modulatory role in
      cutaneous inflammation. In this study, we evaluated the immunoreactivity of the
      neuropeptides vasoactive intestinal polypeptide (VIP) and substance P (SP) in the
      skin of patients with chronic plaque psoriasis, by immunohistochemistry and
      radioimmunoassay. No differences were observed, by immunohistochemistry, in the
      expression and localization of VIP and SP between psoriatic and normal skin.
      Using the radioimmunologic technique on whole skin homogenates, VIP levels were
      significantly increased in psoriatic lesions as compared to normal skin. By
      contrast, SP levels were significantly lower in lesional and non-lesional
      psoriatic skin than in normal skin. In addition, we examined the effect of VIP
      and SP on the proliferation of cultured normal human keratinocytes. VIP (1-28) (1
      nM-1 microM) as well as VIP fragments (10-28) (1 nM-1 microM) and (22-28) (1 nM-1
      microM) stimulated the proliferation of keratinocytes in a dose-dependent manner,
      whereas the VIP fragment (1-12) (1 nM-1 microM) was ineffective. The VIP
      antagonist (N-Ac-Tyr1, D-Phe2)-GRF (1-29)-NH2 (0.1 microM) significantly
      inhibited the VIP effect on keratinocytes. On the other hand, SP (0.1 microM) not
      only failed to stimulate keratinocyte growth, but also blocked the VIP-induced
      stimulation of these cells. The imbalance of cutaneous VIP and SP and their
      disparate effects on the proliferation of normal human keratinocytes in culture
      would suggest that these peptides are involved in the pathogenesis of psoriasis
      and may exert different modulatory activities in the mechanisms underlying the
      psoriatic lesion.

PMID- 1372340
TI  - CHILD syndrome: lack of expression of epidermal differentiation markers in
      lesional ichthyotic skin.
AB  - Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD)
      syndrome is a rare genetic disorder. The epidermal abnormalities associated with
      the unilateral ichthyosis have previously been examined only by morphology. In
      order to describe these abnormalities more completely we analyzed the expression
      of markers of epidermal differentiation (keratins and filaggrin), grew
      keratinocytes in culture, and correlated the results with ultrastructural
      features. Expression of all differentiation markers was significantly reduced or
      absent, whereas keratins K5 and K14 and keratins K6 and K16 were strongly
      expressed in lesional epidermis, suggesting that basal cell keratin expression
      was not down-regulated as in normal epidermis and that lesional keratinocytes
      mature via an abnormal pathway. When removed from the tissue and grown in
      culture, keratinocytes from lesional and non-lesional biopsies had similar phase
      microscopic morphology as well as keratin and profilaggrin expression, in
      contrast to the extreme differences in vivo. Lesional keratinocytes also had
      similar contents of keratin filaments and keratohyalin, but showed abnormal
      accumulation of intercellular vesicles and debris and altered cell-cell and cell
      substratum interaction. Comparison of the results in tissue and in culture
      suggests that systemic or dermal factors influence the abnormal structural
      protein expression and ichthyosiform epidermal differentiation seen in CHILD
      syndrome, but that lesional keratinocytes maintain abnormalities in the secretion
      and accumulation of extracellular material in vitro similar to the lesional
      tissue in vivo.

PMID- 1372341
TI  - Protoporphyrin and long-wave ultraviolet light modulate metabolic events in rat
      peritoneal mast cells.
AB  - We have previously shown that protoporphyrin (PP) plus long-wave ultraviolet
      light (UVA) has an inhibitory effect on the release of histamine from rat
      peritoneal mast cells in response to various stimuli, without compromising cell
      viability. In the present study, we observed that protoporphyrin at a
      noncytolytic dose (3 ng/ml) plus UVA irradiation (0.038 J/cm2) is also able to
      suppress prostaglandin D2 generation by rat peritoneal mast cells in response to
      calcium ionophore A23187, compound 48/80, or anti-IgE antibody by 64%, 92%, and
      100%, respectively. Because of the participation of protein kinase C in stimulus
      secretion coupling in mast cells, we also investigated the effect of PP plus UVA
      on the release of histamine induced by the protein kinase C activator, phorbol 12
      myristate 13-acetate (PMA). PP plus UVA inhibited histamine release induced by
      PMA. The release of histamine induced by the synergistic combination of PMA (50
      nM) and a low dose of calcium ionophore A23187 (0.1 microM) was also inhibited.
      PP plus UVA inhibited the release of histamine induced by the non-fluorescent
      calcium ionophore, 4-Br-A23187, by 47.8%, but had essentially no effect on
      changes in intracellular calcium induced by this stimulus. In contrast, both the
      release of histamine and changes in intracellular calcium stimulated by compound
      48/80 were inhibited. We conclude from these results that PP plus UVA may affect
      both early and late biochemical events involved in mast cell mediator release.

PMID- 1372342
TI  - Nootropic drugs positively modulate alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid-sensitive glutamate receptors in neuronal cultures.
AB  - Micromolar concentrations of piracetam, aniracetam, and oxiracetam enhanced alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-stimulated 45Ca2+
      influx in primary cultures of cerebellar granule cells. Nootropic drugs increased
      the efficacy but not the potency of AMPA and their action persisted in the
      presence of the voltage-sensitive calcium channel blocker nifedipine.
      Potentiation by oxiracetam was specific for AMPA receptor-mediated signal
      transduction, as the drug changed neither the stimulation of 45Ca2+ influx by
      kainate or N-methyl-D-aspartate nor the activation of inositol phospholipid
      hydrolysis elicited by quisqualate or (+-)-1-aminocyclopentane-trans-1,3
      dicarboxylic acid. Piracetam, aniracetam, and oxiracetam increased the maximal
      density of the specific binding sites for [3H]AMPA in synaptic membranes from rat
      cerebral cortex. Taken collectively, these results support the view that
      nootropic drugs act as positive modulators of AMPA-sensitive glutamate receptors
      in neurons.

PMID- 1372343
TI  - First characterization of 6-hydroxytryptamine in the rat midbrain by using
      specific antibodies.
AB  - The visualization of serotonin, 5-methoxytryptamine, and tryptamine in the rat
      midbrain has been made possible by the development of antibodies raised against
      these conjugated molecules. It has been suggested that 6-hydroxytryptamine (6-HT)
      might also be a neurotransmitter in this region. To test this hypothesis, 6-HT
      was synthesized and antibodies were raised in the rabbit. The high avidity (IC50
      = 5 x 10(-9) M) and specificity [cross-reactivity ratio between 6-HT
      glutaraldehyde (G)-bovine serum albumin (BSA) and 5-HT-G-BSA, the most
      immunoreactive compound, was 1,500] rendered these antibodies reliable tools for
      specific molecular detection of 6-HT in the G-fixed tissues. In the dopaminergic
      region, 6-HT immunoreactivity was noted in the substantia nigra but was
      particularly intense in the red nuclei, where it seems to be localized in the
      magnocellular division in the form of large 6-HT neurons. In contrast, there were
      few 6-HT neurons in the raphe nuclei. Thus, 6-HT may be a new putative
      neurotransmitter existing in the red nuclei, in addition to the other
      neurotransmitters already described in this region, in the nigro-rubral pathway,
      and in the rubral projection from the dorsal raphe nuclei. 6-HT is possibly
      implicated in motor control and might exert hallucinogenic properties as do other
      6-hydroxylated indoleamines.

PMID- 1372344
TI  - Drug-induced changes in blood pressure lead to changes in extracellular
      concentrations of epinephrine, dihydroxyphenylacetic acid, and 5
      hydroxyindoleacetic acid in the rostral ventrolateral medulla of the rat.
AB  - Neurochemical changes in the extracellular fluid of the rostral ventrolateral
      medulla (RVLM) were produced by changes in arterial blood pressure. Blood
      pressure was raised or lowered with systemic infusions of phenylephrine or
      nitroprusside and neurochemicals were recovered from RVLM by in vivo
      microdialysis. A dialysis probe 300 microns in diameter and 500 microns in length
      was stereotaxically implanted in the RVLM of the urethane-anesthetized rat.
      Sterile physiological Ringer's solution was perfused at a rate of 1.5
      microliter/min. The perfusate was collected under ice-cold conditions every 15
      min for the assay of epinephrine, dihydroxyphenylacetic acid (DOPAC), 5
      hydroxyindoleacetic acid (5-HIAA), ascorbic acid, and uric acid. After stable
      baseline neurochemical concentrations were achieved, animals were infused with
      phenylephrine or nitroprusside intravenously to raise or lower the blood
      pressure. Increasing blood pressure 50 mm Hg above the baseline value by
      phenylephrine led to a significant reduction in heart rate and a reduction in
      extracellular epinephrine and DOPAC concentrations. The 5-HIAA concentration was
      increased during the hypertensive drug infusion. There were no changes in the
      concentrations of ascorbic acid or uric acid. Hypotension produced by
      nitroprusside (-20 mm Hg) led to neurochemical changes which were the reciprocal
      of those seen during hypertension. During hypotension, heart rate increased as
      did the extracellular fluid epinephrine concentration. The 5-HIAA concentration
      fell with hypotension and remained depressed following the nitroprusside
      infusion. Ascorbic acid and uric acid concentrations did not change during
      hypotension but ascorbic acid did increase after the nitroprusside infusion
      stopped. These data provide direct evidence that epinephrine release in RVLM is
      linked to changes in systemic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372346
TI  - MK-801 increases extracellular 5-hydroxytryptamine in rat hippocampus and
      striatum in vivo.
AB  - The effect of MK-801 (0.25 or 0.5 mg/kg) on the extracellular concentration of 5
      hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rat
      hippocampus and striatum was studied using intracerebral dialysis. The dialysate
      5-HT concentration was dose-dependently increased by MK-801 in both regions. In
      the hippocampus, at the higher drug dose a slow increase in the 5-HIAA level was
      observed, and this became significant 3 h after treatment. In contrast to this,
      the extracellular 5-HIAA content in the striatum was significantly decreased 150
      min after administration of both doses of MK-801. The data are discussed in the
      light of the known behavioural effects of MK-801 and possible N-methyl-D-aspartic
      acid receptor regulation of 5-HT release.

PMID- 1372345
TI  - Octanoic acid produces accumulation of monoamine acidic metabolites in the brain:
      interaction with organic anion transport at the choroid plexus.
AB  - Effects of octanoic acid on monoamines and their acidic metabolites in the rat
      brain were analyzed by HPLC. Octanoic acid (1,000 mg/kg i.p.) elevated
      homovanillic acid levels by 54% in the caudate and 338% in the hypothalamus but
      increased 5-hydroxyindoleacetic acid (5-HIAA) levels in both the caudate and the
      hypothalamus by approximately 50% compared with the control. A lower dose of
      octanoic acid (500 mg/kg) increased 5-HIAA levels by 29% in the caudate and 20%
      in the hypothalamus. However, it did not produce any changes in the concentration
      of homovanillic acid in either the caudate or the hypothalamus. Treatment with
      octanoic acid also failed to change the level of dopamine, serotonin, and 3,4
      dihydroxyphenylacetic acid in the caudate and the hypothalamus. The role of
      carrier-mediated transport in the clearance of 5-HIAA from the rabbit CSF was
      also evaluated in vivo by ventriculocisternal perfusion. Steady-state clearance
      of 5-HIAA from CSF exceeded that of inulin and was reduced in the presence of
      octanoic acid. Because this transport system in the choroid plexus is normally
      responsible for the excretion of the serotonin metabolite from the brain to the
      plasma, accumulation of endogenously produced organic acids in the brain,
      secondary to reduced clearance by the choroid plexus, could be a contributing
      factor in the development of encephalopathy in children with medium-chain acyl
      CoA dehydrogenase deficiency who have elevated levels of octanoic acid
      systematically.

PMID- 1372347
TI  - Chromatographic evidence for the presence of multiple tachykinins in the bovine
      adrenal medulla.
AB  - Among the mammalian tachykinins, substance P (SP) has been shown to be the most
      potent at modulating the response due to nicotinic acetylcholine receptor
      stimulation of bovine adrenal chromaffin cells. SP-like immunoreactivity has been
      detected in nerve terminals innervating the adrenal medulla; however, little is
      known of the presence of other tachykinins in this tissue. In this study, reverse
      phase HPLC was used to fractionate peptides in bovine adrenal medullary extracts,
      and the fractions were analyzed by radioimmunoassay using antisera to SP or
      neurokinin A (NKA). The results show that both NKA- and SP-like
      immunoreactivities are present in the adrenal medulla. The presence of neurokinin
      B is also indicated. The presence of multiple tachykinins in this tissue raises
      questions as to their functions in the adrenal medulla.

PMID- 1372348
TI  - Endothelial cell activation in vasculitis of peripheral nerve and skeletal
      muscle.
AB  - To clarify the role of endothelial cells in the pathogenesis of vasculitis
      affecting peripheral nerve and skeletal muscle, the endothelial expression of
      adhesion molecules and major histocompatibility antigens (MHC) in different
      vasculitic syndromes were studied, and related to the presence of anti
      endothelial cell antibodies (AECA). Increased expression of the intercellular
      adhesion molecule ICAM-1 in vasculitic lesions in nerve and muscle was shown, and
      this was associated with increased expression of MHC class I and II antigens.
      AECA were detected in low titre in only a minority of patients. The findings
      suggest that endothelial cells have a critical role in mediating the tissue
      injury in vasculitis affecting nerve and muscle and that the process is triggered
      by cellular and not antibody-mediated mechanism in the majority of patients.

PMID- 1372350
TI  - Long-term effects of chemotherapy in patients with testicular cancer.
AB  - PURPOSE: Combination chemotherapy regimens that include cisplatin (CDDP) and
      bleomycin (BLE) result in the cure of the majority of patients with malignant
      germ cell tumors of the testis. We investigated the long-term damage of such
      chemotherapy to renal, pulmonary, and hearing function. PATIENTS AND METHODS:
      Forty-three patients with disseminated testicular carcinoma were studied 1.5 to
      9.3 years (median, 4.1 years) after completion of chemotherapy. All 43 patients
      received CDDP; of these, 39 also received BLE, 27 vinblastine (VLB), and 27
      etoposide (VP-16). Mean cumulative doses of individual cytotoxic drugs
      administered were CDDP 483 mg/m2 (range, 189 to 1,173 mg/m2), BLE 160 mg/m2
      (range, 81 to 311 mg/m2), VLB 31 mg/m2 (range, 19 to 158 mg/m2), and VP-16 667
      mg/m2 (range, 242 to 1,455 mg/m2). RESULTS: In the majority of cases, values of
      renal, pulmonary, and hearing function were within the normal range before
      treatment. An initial decrease in renal, pulmonary, and hearing function was
      observed, with recovery of pulmonary function at late follow-up. On average, a
      decrease of 15% in creatinine clearance rates was observed at late follow-up.
      Long-term effect on audiometric function was considerable, but frequencies
      affected were outside the range of conversational speech. With multivariate
      analysis, no overall relation between the cumulative doses of the individual
      drugs and the loss in organ function was found; the cumulative doses of CDDP and
      BLE only contributed approximately 30% to the loss in renal function and vital
      capacity, respectively. CONCLUSION: Chemotherapy-induced pulmonary toxicity is
      reversible, whereas nephrotoxicity and ototoxicity are not. However, the long
      term effects of chemotherapy in testicular cancer patients were minor and not
      invalidating.

PMID- 1372349
TI  - High-dose intravenous human immunoglobulin in polymyositis resistant to
      treatment.
AB  - Two patients were treated with treatment-resistant polymyositis with intravenous
      immunoglobulin over four days at a dose of 0.4 g/kg/day. Clinical recovery
      followed within two months. Serum creatine kinase (CK) activity decreased to
      normal, and a clear improvement in muscle strength was observed. One patient
      showed neither clinical relapses nor increase in serum CK activity after 20
      months. The other showed a mild increase in serum CK activity after 24 months and
      was successfully retreated with intravenous immunoglobulin. There were no
      significant adverse side effects.

PMID- 1372352
TI  - Susceptibility of HIV-1 isolates to zidovudine: correlation between widely
      applicable culture test and PCR analysis.
AB  - Thirteen isolates of human immunodeficiency virus type 1 (HIV-1) obtained in
      coculture with peripheral blood lymphocytes were tested for in vitro
      susceptibility to zidovudine (ZDV). Seven isolates were obtained from patients
      who had never been treated with ZDV and six from patients receiving the drug. The
      seven isolates from untreated patients and four of six from treated patients were
      susceptible to ZDV. The two isolates from the patients treated for the longest
      periods were resistant to the drug. The presence of mutations at critical
      positions of the reverse transcriptase gene was investigated by direct sequencing
      of polymerase chain reaction (PCR)-amplified DNA and four isolates were found to
      be mutants. An isolate from an untreated patient showed a change at residue 70 of
      the reverse transcriptase and an isolate from a patient treated for 4 months
      showed a change at residue 67. A change at residue 215 was found only for the two
      drug-resistant isolates, which correlated with the results obtained by Larder et
      al. using isolates from MT-2 cell cocultures. These results suggest that any HIV
      isolate provided by conventional coculture could be confidently tested for ZDV
      susceptibility in order to study the emergence of resistance during long-term
      therapy.

PMID- 1372351
TI  - Activated lymphocyte subsets in adult periodontitis.
AB  - The activation state of T and B lymphocytes in the peripheral blood of
      periodontitis patients may be a reflection of disease activity. We have utilized
      2- and 3-color flow cytometric analyses using a new chromophore, peridinin
      chlorophyll A protein, and conventional dyes, fluorescein isothiocyanate and
      phycoerythrin, conjugated to monoclonal antibodies against activated lymphocyte
      surface markers to measure blood lymphocyte subsets from 18 periodontitis
      patients and 16 periodontally healthy control subjects. Two-color flow cytometric
      analysis demonstrated that the frequency of CD4+ and CD5+ T cells, CD20+ B cells,
      and CD16+ NK (natural killer) cells were increased in periodontitis patients. Of
      particular interest, CD4+ activated "memory" T cells, CD5+ B cells, and CD56+ NK
      effector cells were increased significantly in periodontitis patients (p less
      than 0.05). While the relationship of lymphocyte activation to periodontal
      disease activity remains unclear, there may be potential for using 2- and 3-color
      flow cytometry to subcategorize periodontitis patients into high- and moderate
      risk groups.

PMID- 1372353
TI  - Specific antibody responses to synthetic peptides of HIV-1 p17 correlate with
      different stages of HIV-1 infection.
AB  - Antibodies were determined against five synthetic peptides (epitopes) of HIV-1
      p17 in the sera of an immunologically and clinically well-characterized cohort (N
      = 292) of HIV-1 seronegative and HIV-1 seropositive high-risk homosexual men, HIV
      1 seropositive i.v. drug abusers (IVDA), and AIDS patients. The synthetic
      peptides, representing the entire HIV-1 p17 protein sequence were: HGP-33 (aa 1
      33), HGP-19 (aa 34-52), HGP-35 (aa 51-85), HGP-30 (aa 85-114), and HGP-17 ala (aa
      114-131). The presence of one or more peptide-specific antibodies in the sera of
      all of the HIV-1 p17-positive subjects indicated that all five peptides contain B
      cell epitopes. No antibodies were found in the sera of heterosexual controls, HIV
      1 seronegative high-risk men, or asymptomatic HIV-1 seropositive but p17 antibody
      negative study subjects. Significant differences in antibody recognition profiles
      to the peptide epitopes were found among the various study groups. A
      significantly higher proportion of HIV-1 seropositive IVDA had antibodies
      specific to HGP-17 ala (aa 114-131), HGP-35 (aa 51-85), and HGP-33 (aa 1-33)
      compared to the HIV-1 p17-positive asymptomatic homosexuals. The epitope-specific
      antibody responses reflected the clinical status of the HIV-1-infected study
      subjects, and declined to nondetectable levels as the patient progressed to
      ARC/AIDS. This decline preceded by several months the reduction in the antibody
      titer against the intact HIV-1 p17 and p24 proteins.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1372354
TI  - T-lymphocyte responses to Pneumocystis carinii in healthy and HIV-positive
      individuals.
AB  - Pneumocystis carinii pneumonia (PCP) is a well-recognized cause of morbidity in
      patients with impaired T-cell function. In this study of cellular immunity to P.
      carinii, peripheral blood mononuclear cells from 25 HIV antibody-positive (HIV+)
      patients and 11 healthy individuals were stimulated in vitro with P. carinii
      antigen. The responding T-cell blasts were cocultured with autologous P. carinii
      antigen-pulsed macrophages to measure P. carinii-specific cytolytic T-lymphocyte
      activity (CTL). T-cell blasts from two healthy donors were used to generate P.
      carinii-specific clones by limiting dilution. T cells from HIV+ patients
      proliferated less to P. carinii antigen than T cells from healthy volunteers. In
      contrast, the level of specific cytotoxicity was identical in all groups when
      equal numbers of CTLs were used. Within the group of symptomatic patients, CTL
      activity was higher in those with a history of PCP (p = 0.033). Pneumocystis
      carinii antigen-specific T-cell clones proved to be CD4+ and MHC class II
      restricted; six of eight clones tested showed P. carinii-specific cytolytic
      activity. Cell-mediated immune response to P. carinii in healthy individuals
      include CD4+, class II MHC-restricted T cells with P. carinii-specific
      cytotoxicity. There is an increasing loss of P. carinii-specific proliferative
      responses in HIV+ patients as disease progresses, but a cytotoxic response is
      still detected in the absence of proliferation.

PMID- 1372355
TI  - Use of recombinant canine granulocyte colony-stimulating factor to decrease
      myelosuppression associated with the administration of mitoxantrone in the dog.
AB  - Ten dogs were given mitoxantrone at a dose of 5 mg/m2 body surface area
      intravenously. Recombinant canine granulocyte colony-stimulating factor (rcG-CSF)
      was administered subcutaneously daily for 20 days after an infusion of
      mitoxantrone in five of these dogs to determine the effect of the hematopoietic
      growth factor on the duration and severity of myelosuppression. The median
      neutrophil counts dropped below normal (less than 3,000/uL) for 2 days in the
      dogs that received rcG-CSF, and for 5 days in the dogs that received only
      mitoxantrone. Four of five dogs not treated with rcG-CSF and none of those
      receiving rcG-CSF developed serious neutropenia (less than 1,500/uL). The
      neutrophil counts were significantly (P less than 0.05) higher in the rcG-CSF
      treated dogs at all time points except before the administration of the colony
      stimulating factor, and the sixth day after the mitoxantrone was administered.
      These findings demonstrate that rcG-CSF is capable of reducing the duration and
      severity of mitoxantrone-induced myelosuppression.

PMID- 1372356
TI  - Common mechanisms govern the expression of p21ras and class II MHC antigens in
      the murine placenta.
AB  - It has been shown that there is an inverse as well as a direct correlation
      between class II MHC antigen expression and the p21ras protein, depending on the
      cell type. By using trophoblastic cells derived from the spongiotrophoblast and
      labyrinthine trophoblast, the two major components of the murine placenta, we
      have examined the p21ras expression in these populations and how this correlates
      with the induction of class II MHC antigens. It has been shown that although only
      a small number of cells express the p21ras and class II proteins, they can be
      induced to express higher levels of these markers by two different treatments.
      Thus, gamma-interferon (gamma-IFN) induces p21ras and class II protein expression
      in spongiotrophoblast-derived cells, whereas 5-Azacytidine (5-AzaC) induces
      expression of these antigens in labyrinthine trophoblast-derived populations.
      Furthermore, it has been demonstrated that there is a direct correlation between
      the two markers, as blocking antibody to p21ras cancels the ability of gamma-IFN
      and 5-AzaC to induce class II antigens. As previous work from this laboratory has
      shown that in vivo class II induction in the placenta leads to fetal abortion,
      the present results suggest that both proteins are involved in a common signal
      transduction pathway which may lead to disruption of fetal membranes and fetal
      loss.

PMID- 1372357
TI  - Rare causes of elevated maternal serum alpha-fetoprotein. A report of three
      cases.
AB  - Three rare conditions--amniotic band disruption sequence, placental chorioangioma
      and congenital nephrosis--were diagnosed in midtrimester because of elevated
      maternal serum alpha-fetoprotein. The diagnosis is important for genetic
      counseling and obstetric follow-up.

PMID- 1372358
TI  - Syntheses and thymidylate synthase inhibitory activity of the poly-gamma-glutamyl
      conjugates of N-[5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N
      methylamino ]-2-thenoyl]-L-glutamic acid (ICI D1694) and other quinazoline
      antifolates.
AB  - Thirteen poly-gamma-glutamates derived from several novel antifolates have been
      synthesized by a convergent route. The syntheses of poly-gamma-glutamyl
      conjugates of N-[5-[N-(3,4-dihydro-2- methyl-4-oxoquinazolin-6-ylmethyl)-N
      methylamino]-2-theno yl]-L-glutamic acid (8) (ICI D1694), 2-desamino-N10
      propargyl-5,8-dideazafolic acid (6), 2-desamino-2-methyl-N10-propargyl-5,8
      dideazafolic acid (7), 2-desamino-2-methyl-N10-propargyl-2'-fluoro-5,8
      dideazafolic acid (9), and 2-desamino-2-methyl-4-chloro-N10-propargyl-2'-fluoro
      3,5,8-trideazafo lic acid (11) are described. A key step in the route involves
      coupling of an alpha-tert-butyl-protected poly-gamma-glutamate of the required
      chain length to the appropriate 5,8-dideazapteroic acid, obtained by
      carboxypeptidase G2 cleavage of the parent monoglutamate, if available, or by
      chemical synthesis. Deprotection with trifluoroacetic acid in the final step gave
      the desired poly-gamma-glutamyl antifolates as their trifluoroacetate salts. As
      inhibitors of thymidylate synthase, these polyglutamates were more potent in
      every case than the corresponding non-polyglutamylated drug.

PMID- 1372359
TI  - Novel benzothiophene-, benzofuran-, and naphthalenecarboxamidotetrazoles as
      potential antiallergy agents.
AB  - The synthesis and antiallergic activity of a series of novel benzothiophene-,
      benzofuran-, and naphthalenecarboxamidotetrazoles are described. A number of the
      compounds inhibit the release of histamine from anti-IgE stimulated basophils
      obtained from allergic donors. Optimal inhibition is exhibited in benzothiophenes
      with a 3-alkoxy substituent in combination with a 5-methoxy, 6-methoxy, or a 5,6
      dimethoxy group. Compound 13c (CI-959) also inhibited respiratory burst of human
      neutrophils and the release of mediators from anti-IgE-stimulated human chopped
      lung.

PMID- 1372361
TI  - Isolation of a novel siderophore from Pseudomonas cepacia.
AB  - A novel iron-binding compound was identified in ethyl acetate extracts of the
      supernates from Pseudomonas cepacia cultures. This compound, named azurechelin,
      was produced by 88% of P. cepacia strains isolated from the respiratory tract.
      Production of azurechelin was regulated by the iron concentration in the culture
      medium. Azurechelin enhanced the growth of P. cepacia in a medium containing
      transferrin 200 mg/L. Azurechelin released iron from transferrin in an
      equilibrium dialysis assay, suggesting that it could complete with transferrin
      for iron. Azurechelin could also stimulate iron uptake by P. cepacia. This
      siderophore appeared to have a novel structure with neither the typical
      characteristics of catechol nor of hydroxamate compounds.

PMID- 1372360
TI  - Localisation of the mitogenic epitope of staphylococcal enterotoxin B.
AB  - Limited digestion of staphylococcal enterotoxin B (SEB) with trypsin resulted in
      the generation of a 12-Kda amino-terminal fragment and a 17-Kda carboxy-terminal
      fragment which were isolated by preparative iso-electric focusing. The carboxy
      terminal fragment exhibited significant mitogenic activity for murine
      splenocytes, whereas the isolated amino-terminal fragment possessed little
      detectable mitogenic activity. Monoclonal antibodies (MAbs) specific for the
      carboxy-terminal fragment neutralised most of the mitogenic activity of both the
      intact toxin and the carboxy-terminal fragment. MAbs specific for the amino
      terminal fragment had no detectable neutralising activity. These results support
      the hypothesis that the epitope(s) responsible for mitogenic activity is located
      in the carboxy-terminal region of SEB.

PMID- 1372362
TI  - Host factors versus virulence-associated bacterial characteristics in neonatal
      and infantile bacteraemia and meningitis caused by Escherichia coli.
AB  - Possession of P fimbriae, virulence-associated O and K antigens, haemolysin and
      aerobactin production, and susceptibility to 10 antimicrobial agents were studied
      in 63 Escherichia coli strains isolated from blood or CSF of infants who were
      grouped according to their clinical characteristics. These isolates were compared
      with 35 faecal E. coli strains from healthy infants. Individual virulence factors
      showed a relatively weak association with invasive infection except for P
      fimbriae in urosepsis and aerobactin production in meningitis. Combinations of
      factors were generally more predictive for defining virulent clones, particularly
      in infants defined as being at normal risk of developing septicaemia. Thus, 62%
      of isolates from such infants had characteristics typical of previously described
      uropathogenic or meningitis-associated clones of E. coli, compared with 32% of
      the isolates from high-risk infants (i.e., those defined as being at high risk of
      developing septicaemia) and only 9% of the faecal isolates (p less than 0.001 and
      less than 0.05, respectively). Overall, 45% of the episodes of invasive infection
      were caused by such clones, whereas risk factors (conditions considered to be
      associated with increased risk of invasive infection) were present in 59% of the
      infected infants (39% in meningitis and urosepsis, 78% in cryptogenic septicaemia
      and untreated bacteraemia). The results indicated that bacterial factors played a
      significant causative role in neonatal meningitis and urosepsis, particularly in
      normal-risk infants, whereas predisposing host factors contributed greatly to
      cryptogenic septicaemia and untreated bacteraemia.

PMID- 1372363
TI  - Identification of an endoflagellar associated protein in Borrelia burgdorferi.
AB  - DNA of Borrelia burgdorferi was cleaved by the endonuclease EcoRI and ligated
      with the bacteriophage expression vector lambda gt11. After infection of the
      Escherichia coli strain Y1089, the plaques of recombinant phages were screened
      with a B. burgdorferi antiserum (human) for fusion proteins containing borrelia
      antigen.s A positive clone produced a hybrid protein (p200) of c. 200 Kda. The
      corresponding native borrelia protein (p97) was identified as having an Mr of 97
      Kda. To localise protein p97 in the B. burgdorferi cell, immunoelectronmicroscopy
      and a Western blot of isolated flagella were used. Antibodies directed against
      proteins p200 and p97 recognised epitopes associated with the flagella.

PMID- 1372364
TI  - Variation of the O antigen of Campylobacter jejuni in vivo.
AB  - During the course of a clinical study on patients with campylobacteriosis, three
      consecutive isolates of Campylobacter jejuni from the same patient were sent for
      O-serotyping. Marked differences in the specificities of the O antigens of the
      isolates were observed between the first and third isolates when a passive
      haemagglutination assay system developed for serotyping C. jejuni was used.
      Differences in specificity were also demonstrated by immunoblots of
      lipopolysaccharides (LPS) from proteinase K-digested whole cells. The three
      isolates could not be distinguished either by restriction endonuclease analysis
      of chromosomal DNA, by gel electrophoresis of whole-cell proteins or by silver
      stained LPS gels, thus providing evidence that they were of the same strain and
      that antigenic variation had occurred in vivo.

PMID- 1372365
TI  - Parameters affecting transcription termination by Escherichia coli RNA
      polymerase. I. Analysis of 13 rho-independent terminators.
AB  - Escherichia coli RNA polymerase can terminate transcription efficiently at rho
      independent terminators in a purified transcription system in the absence of
      accessory factors. This process of "intrinsic termination" involves direct
      recognition of the terminator by the core RNA polymerase, and provides an
      important model system for the study of the molecular interactions involved in
      the switch between elongation and termination. We have analyzed the intrinsic
      termination efficiency (%T) of 13 rho-independent terminators, under a variety of
      in vitro reaction conditions. Although all of these sites share the general
      sequence features of typical rho-independent terminators, we find a wide range of
      %T (2% to 90%) for the different sites under our standard transcription
      conditions. While %T for a particular site is characteristic of that site, the
      efficiency can be altered considerably by the nature and concentration of salts
      in the reaction, by alteration of the concentrations of the nucleoside
      triphosphate substrates, or by transcription from supercoiled rather than linear
      templates. Surprisingly, different conditions can alter %T to a different extent
      for different terminators. For neutral salts such as potassium chloride or
      potassium glutamate, changes in the range from 0.1 to 1 M affect %T for different
      terminators in a distinct manner, depending on the terminator and the anion
      involved. At some sites, %T is greatly increased by Cl- concentrations up to 1 M,
      while at other sites %T is reduced or unaffected by these conditions. At some
      sites K+ concentrations up to 1 M give a modest increase in %T, while at other
      sites %T is slightly reduced under the same conditions. Thus the actual values of
      %T, as well as the order of terminator sites ranked according to %T, can be
      altered greatly according to the choice of reaction conditions. Reduction of the
      Mg2+ concentration below 1 mM has a dramatic and quite different effect,
      enhancing termination to approximately 100% for all terminators tested.
      Transcription of supercoiled DNA templates gives somewhat reduced %T as compared
      with linear DNA templates. However, the effect is no greater than twofold. Our
      results are not consistent with those expected for models in which %T is
      determined by the differential stability of DNA, RNA and hybrid duplex structures
      at the melted region in the transcription complex. Thus, the Cl anion does not
      affect the stability of nucleic acid duplexes even at 1 M concentrations, but can
      enhance termination tenfold. Also, the alterations of monovalent cation
      concentration that affect %T are not expected to have a differential effect on Tm
      for DNA, RNA and hybrid duplexes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1372366
TI  - Parameters affecting transcription termination by Escherichia coli RNA. II.
      Construction and analysis of hybrid terminators.
AB  - Rho-independent terminators are characterized by two major functional regions,
      one upstream from the termination site having a sequence capable of forming an
      RNA hairpin in the nascent transcript, the second extending, from the base of
      this hairpin, seven to nine nucleotides along the transcript to the actual sites
      of termination (3'-tail region). This latter region of the transcript is often
      rich in uridine residues. Both regions are postulated to play central roles in
      the termination process. We have constructed a series of hybrid rho-independent,
      transcription terminators in which sequences upstream and downstream from the RNA
      hairpin for the Escherichia coli trp attenuator (trpatt+) are interchanged with
      sequences from trpatt mutant (1419) or from the phage T7 early terminator (T7Te).
      Similar hybrids have been constructed for T7Te, replacing flanking sequences with
      trpatt regions. The effects of such changes on transcription termination have
      been tested in vitro with purified E. coli RNA polymerase to determine the
      intrinsic termination efficiency (%T) of each hybrid terminator. Both the trpatt+
      terminator and T7Te are highly efficient rho-independent terminators in vitro.
      However, replacement of trpatt+ sequences upstream and downstream from the RNA
      terminator hairpin with the comparable T7Te sequences reduces %T dramatically,
      suggesting that the RNA-terminator hairpin does not function independently from
      its flanking regions. Regions downstream from the actual termination/release site
      are shown to be of considerable importance in determining %T for terminators
      bearing the T7Te or trpatt1419 3'-tail region, but have little effect on
      terminators with the trpatt+ 3'-tail region. For terminators bearing the T7Te or
      trpatt1419 3'-tail region that are inefficient, efficient termination is restored
      by elevated concentrations of KCl in the reaction. The results do not fit well
      with models for termination in which %T is determined by a two-step process in
      which the terminator-RNA hairpin, and a seven to 12 base-pair DNA-RNA hybrid
      structure rich in uridine residues, act independently to cause the polymerase to
      pause, and to release the transcript, respectively. DNA sequences both upstream
      and downstream from these regions, as well as DNA sequences downstream from the
      transcript termination site, can significantly affect the termination process.
      Conversely, terminators lacking a 3'-tail region rich in uridine residues can be
      highly efficient, but only when joined with appropriate sequence immediately
      downstream from the termination site. This suggests that the 3'-tail region acts
      in some manner other than the formation of an unstable DNA-RNA hybrid that
      facilitates termination.

PMID- 1372367
TI  - Gliotoxin: inhibitor of poliovirus RNA synthesis that blocks the viral RNA
      polymerase 3Dpol.
AB  - The mode of action of gliotoxin against poliovirus has been analyzed in detail.
      This fungal metabolite inhibits the appearance of poliovirus proteins when
      present from the beginning of infection but has no effect on viral translation
      when added at late times. In agreement with previous findings, this toxin
      potently inhibited the incorporation of [3H]uridine into poliovirus RNA soon
      after its addition to the culture medium. Analysis of the synthesis of poliovirus
      plus- or minus-stranded RNA in the presence of gliotoxin suggests that this
      compound effectively hampered both processes. This result contrasts with the mode
      of action of other inhibitors of poliovirus RNA synthesis, such as guanidine or
      flavones, that selectively block plus-stranded RNA synthesis and suggests that
      the target of gliotoxin differs from the target of guanidine, i.e., poliovirus
      protein 2C. Indeed, gliotoxin was found to be a potent inhibitor of poliovirus
      RNA synthesis in cell-free systems, using membranous crude replication complexes,
      a reaction that is not blocked by guanidine or Ro 09-0179. Moreover, in vitro
      activity of the purified poliovirus polymerase 3Dpol was efficiently inhibited by
      gliotoxin. These results indicate that this toxin acts on the poliovirus
      polymerase 3Dpol, providing the first description of an inhibitor of this viral
      enzyme.

PMID- 1372368
TI  - Cross-reactive and serotype-specific antibodies against foot-and-mouth disease
      virus generated by different regions of the same synthetic peptide.
AB  - Synthetic peptides based on the VP1 proteins of two serotypes of foot-and-mouth
      disease virus (FMDV) and having the general formula C-C-(200-213)-P-P-S-(141-158)
      P-C-G induce heterologous as well as homologous protection against challenge.
      Substitution of the sequence consisting of residues 200 to 213 (200-213 sequence)
      with a second copy of the homologous 141-158 sequence (i.e., homodimers) resulted
      in failure of either serotype peptide to protect heterologously. The antiviral
      and antipeptide titers of sera from guinea pigs immunized with the homodimeric
      141-158 peptides showed serotype specificity and, with the data from the
      heterodimeric peptide vaccines, suggested that the C-terminal 141-158 sequence
      was more effectively recognized by the immune system than the N-terminal
      sequence. Whereas heterologous antiviral titers as measured by enzyme-linked
      immunosorbent assay and virus neutralization tests have not been observed with
      sera from cross-protected animals, epitope-mapping studies established that there
      was heterologous recognition of an octapeptide within the 200-213 sequence. That
      the 200-213 sequence was required for the induction of heterologous protection
      was also confirmed with a number of peptides, including hybrids based on the 200
      213 sequence of one virus and the 141-158 sequence of a second virus. Thus,
      peptides of the general formula given above induce serotype-specific and serotype
      cross-reactive protective antibodies and are unique in their induction of
      significant levels of heterologous protection, a property which has never been
      reported for whole FMDV vaccines.

PMID- 1372369
TI  - Homologous recombination of copackaged retrovirus RNAs during reverse
      transcription.
AB  - According to prevailing models, the high frequency of recombination in
      retroviruses occurs during reverse transcription of two genetically different
      genomes copackaged into virion particles. This view has been tested in our
      studies of the mechanism of recombination within homologous sequences of two
      retroviral genomes during a single round of virus replication and in the absence
      of helper virus. The recombination substrates were Moloney murine leukemia virus
      based vectors, each of which contains an altered defective neomycin gene (neo)
      under the transcriptional control of the 5' long terminal repeat; the 3'
      sequences of each construct contain either the Moloney murine leukemia virus or
      simian virus 40 large-T polyadenylation sequence. One neo gene contained a linker
      insertion mutation at the 5' end (neo minus), and the other contained a deletion
      and linker insertion at the 3' end (neo delta 3). Each of the mutant neo
      constructs was introduced into the packaging helper cell line psi 2 by sequential
      cotransfection, and individual psi 2 double transformants were selected.
      Supernatant fluids from the cloned psi 2 double transformants were used to infect
      NIH 3T3 cells, and recombinant neo+ proviruses were detected by their ability to
      confer G418 resistance during infection of NIH 3T3 cells. Our results show that
      (i) recombination between a homologous sequence of about 560 bp occurred with a
      frequency of about 10(-4) per virus replication cycle; (ii) recombination
      occurred only after the viral RNAs had been packaged into particles, i.e.,
      recombination between the two vector DNAs or between viral RNAs prior to
      packaging was not detected; and (iii) copackaging of two different genomic RNAs
      as a heterodimer is a prerequisite for recombination. Furthermore, our results
      indicate that recombination can occur during the DNA negative-strand synthesis of
      reverse transcription.

PMID- 1372371
TI  - Generation of "natural killer cell-escape" variants of Pichinde virus during
      acute and persistent infections.
AB  - Pichinde virus (PV) strain AN 3739 was determined to be sensitive to natural
      killer (NK) cells in vivo by enhanced replication in NK-cell-depleted mice. An NK
      sensitive subclone (PV-NKs1) was serially passed in mice whose NK cells had
      previously been activated by an interferon inducer, and two plaque isolates were
      shown to be resistant to NK cells but not to interferon. Inoculation of severe
      combined-immunodeficient mice with PV-NKs1 led to a persistent infection
      resulting in an NK-resistant viral population. This is the first demonstration of
      the isolation of viral "NK-escape" variants, as defined by the ability of the
      virus to replicate in vivo.

PMID- 1372370
TI  - Diversity of T-cell receptors in virus-specific cytotoxic T lymphocytes
      recognizing three distinct viral epitopes restricted by a single major
      histocompatibility complex molecule.
AB  - Cytotoxic T lymphocytes (CTL) recognize virus peptide fragments complexed with
      class I major histocompatibility complex (MHC) molecules on the surface of virus
      infected cells. Recognition is mediated by a membrane-bound T-cell receptor (TCR)
      composed of alpha and beta chains. Studies of the CTL response to lymphocytic
      choriomeningitis virus (LCMV) in H-2b mice have revealed that three distinct
      viral epitopes are recognized by CTL of the H-2b haplotype and that all of the
      three epitopes are restricted by the Db MHC molecule. The immunodominant Db
      restricted CTL epitope, located at LCMV glycoprotein amino acids 278 to 286, was
      earlier noted to be recognized by TCRs that consistently contained V alpha 4
      segments but had heterogeneous V beta segments. Here we show that CTL clones
      recognizing the other two H-2Db-restricted epitopes, LCMV glycoprotein amino
      acids 34 to 40 and nucleoprotein amino acids 397 to 407 (defined in this study),
      utilize TCR alpha chains which do not belong to the V alpha 4 subfamily. Hence,
      usage of V alpha and V beta in the TCRs recognizing peptide fragments from one
      virus restricted by a single MHC molecule is not sufficiently homogeneous to
      allow manipulation of the anti-viral CTL response at the level of TCRs. The
      diversity of anti-viral CTL likely provides the host with a wider option for
      attacking virus-infected cells and prevents the emergence of virus escape mutants
      that might arise if TCRs specific for the virus were homogeneous.

PMID- 1372372
TI  - Pneumocystis carinii in corticosteroid-treated voles: a comparison of three
      different staining methods.
AB  - Pneumocystis carinii (PC) is an opportunistic pathogen which causes clinical
      disease in immunocompromised hosts. Three different staining protocols were
      employed to detect this organism in lung samples of corticosteroid treated voles
      in order to discover a suitable method for large-scale screening. The procedures
      employed were: Grocotts methenamine silver (GMS)-stained paraffin sections,
      toluidine blue O-stained impression smears, and methenamine-silver-stained frozen
      sections. GMS-stained paraffin sections were relatively easy to interpret and
      gave more positive results than the other methods. It seemed to be the
      satisfactory method for large-scale population analyses. An unexpected result was
      that methylprednisolone treatment did not induce in voles a similarly fatal
      pneumocystosis infection as occurred in rats. All infections found in voles were
      mild. This might be due to species-dependent differences in metabolizing
      methylprednisolone.

PMID- 1372373
TI  - Endothelial function in thrombosis and thrombolysis.
AB  - The localization of tissue factor (TF) in atherosclerotic plaques of human aortas
      was immunohistochemically examined using rabbit anti-IgG against recombinant TF,
      which was expressed in E. coli. TF, the initiator of the extrinsic coagulation
      pathway, was ubiquitously present in atherosclerotic intima, and was expressed
      mainly by macrophages, but not by endothelial cells. It has been suggested that
      some macrophages in atherosclerotic intima co-express both molecules of TF and
      platelet-derived growth factor-B chain. We have developed a morphometrically
      quantitative in vitro assay for angiogenesis, using endothelial cultures on
      collagen gel incorporating plasminogen. With this method, we have obtained
      findings suggesting that plasminogen and plasminogen activators (PAs), especially
      urokinase-type PA (uPA) derived from endothelial cells, enhance angiogenic
      activity, probably by increasing endothelial migration. uPA was
      immunohistochemically observed to be primarily cell-associated on the focal
      contract areas, probably via its receptors on endothelial cells. These findings
      may support the hypothesis that the activation and regulation of the pericellular
      fibrinolysis system is closely related to angiogenesis.

PMID- 1372375
TI  - Alpha-fetoprotein production by hepatocellular carcinoma is prognostic of poor
      patient survival.
AB  - Immunohistochemistry using the avidin-biotin-peroxidase complex method was
      performed to study the production of alpha-fetoprotein (AFP) in hepatocellular
      carcinoma (HCC) tissue specimens which were obtained surgically. The relationship
      between staining for AFP and serum AFP levels or pathological findings was
      examined. The prognosis of the patients with HCC who underwent curative hepatic
      resections was studied with respect to the staining for AFP in their tumors. The
      mean serum AFP level in patients with positive AFP staining was significantly
      higher than in those with negative AFP staining. No significant relationship was
      found between AFP positivity and tumor size, tumor encapsulation, degree of
      vascular invasion, or the histological differentiation grade of the tumor. The
      patients with AFP-positive carcinomas had a poorer prognosis than did those with
      AFP-negative carcinomas (5-year survival rate of AFP-positive and negative groups
      were 26.7% and 56.5%, respectively.

PMID- 1372374
TI  - Immunohistochemical characteristics of adenosquamous carcinoma of the pancreas.
AB  - Six patients with adenosquamous carcinoma (ASqC) of the pancreas were studied
      clinicopathologically and immunohistochemically. In five of six ASqC tumors, both
      malignant squamous and glandular elements were reactive with CA 19-9, ST 439, and
      keratin antibodies. In contrast, a portion of the glandular element in the
      remaining one ASqC was reactive with CA 19-9 and ST 439 antibodies, but that of
      the squamous cell carcinoma (SqCC) was not reactive. However, SqCC of this tumor
      was intensely reactive with keratin antibody. These immunohistochemical results
      suggest that the histogenesis in one ASqC tumor was different from that of the
      other 5 ASqCs, and that this tumor may be a collision tumor rather than
      transformation to SqCC from adenocarcinoma, which is a very rare pattern of
      histogenesis in ASqC. The patients with ASqC of the pancreas showed shorter
      survivals following operations because of systemic metastasis including liver
      metastasis.

PMID- 1372376
TI  - Prostate-specific antigen, digital rectal examination, and transrectal ultrasound
      in predicting the probability of cancer.
AB  - Over a 4 1/2 year period, 1,940 asymptomatic men were entered in a prostate
      cancer detection program consisting of digital rectal examination (DRE), prostate
      specific antigen (PSA), and transrectal prostate ultrasound (TRUS). Four hundred
      and sixteen biopsies were performed resulting in the diagnosis of 79 cancers; 82%
      had clinically organ confined tumors. A recommendation for biopsy was made in 260
      (62%) based on the TRUS alone, 55 (13%) by DRE alone, 92 (22%) when the DRE and
      TRUS were both abnormal, and in 9 (2.2%) cases when only PSA levels were
      elevated. The DRE, PSA, and TRUS were abnormal in 1,261 (65%), 989 (51%), and
      1,552 (80%) of the patients with cancer, respectively. Prostate cancer detection
      increased as the serum PSA level increased above 4 ng/ml. The positive predictive
      value of both DRE and TRUS were significantly influenced by an elevated PSA, (P =
      .042 and P less than .00005, respectively). The results of this study support the
      idea that, although the prostate cancer detection rate is influenced by these
      three modalities and the detection rate of localized disease can be improved by
      early detection programs, its effect on mortality rates remains undefined at this
      time.

PMID- 1372377
TI  - Influence of preoperative treatment and surgical operation on immune function of
      patients with esophageal carcinoma.
AB  - Multiple immunological parameters, including total lymphocyte count, lymphocyte
      subpopulations (CD2+, CD19+, CD3+, CD4+ and CD8+), phytohemagglutinin (PHA)
      response, and natural killer (NK) activity, were measured in 66 patients with
      previously untreated esophageal carcinoma. The influence of preoperative
      treatment and/or surgical operation on the immune function were evaluated in 40
      patients. The PHA response and NK activity of the patients with esophageal
      carcinoma were 229 +/- 103 S.I.% and 18.5 +/- 11.9% lysis, respectively, and were
      significantly depressed as compared with the control. The CD4+/CD8+ ratio, PHA
      response, and NK activity in stage IV were also significantly depressed compared
      to that in stages I-III. Preoperative treatment induced significant reductions in
      the total lymphocyte count (1,994 +/- 644 to 670 +/- 274/mm3), PHA response (219
      +/- 77 to 159 +/- 59 S.I.%), and NK activity (19.7 +/- 13.2 to 11.1 +/- 10.3%
      lysis) as well as a significant gradual decrease in the CD4+/CD8+ ratio (2.09 +/-
      1.42 to 0.69 +/- 0.48), while the surgical operation significantly influenced
      only the total lymphocyte count. This study demonstrates that preoperative
      treatment induces a more pronounced influence on the immune function than
      surgical operation alone, in patients with esophageal carcinoma in which the
      immune function is disturbed prior to these treatments.

PMID- 1372378
TI  - Androgen effect on prostate specific antigen secretion.
AB  - Prolonged parenteral androgen therapy for 1 year resulted in the hypersecretion
      of prostate specific antigen (PSA) in a patient with no clinical evidence of
      prostate carcinoma, who had been treated with diethylstilbestrol (DES) for 9
      years. The PSA level declined to normal values upon temporary discontinuation of
      androgen therapy and increased again upon resumption of treatment. This case
      seems to confirm the regulatory effect of androgens of PSA secretion and to
      suggest a possible "rebound" elevation of PSA in patients with androgen
      deprivation treated with testosterone replacement. The estrogen suppressed
      prostatic epithelial cells were able to respond to androgen stimulation with a
      steady increase in the PSA secretion and positive immunohistochemical PSA
      staining.

PMID- 1372379
TI  - Molecular features of CD34: a hemopoietic progenitor cell-associated molecule.

PMID- 1372380
TI  - Tubulomembranous lesions in p-bromophenylacetylurea neuropathy reflect local
      stasis of fast axonal transport: evidence from electron microscopic
      autoradiography.
AB  - The source of the membranous materials that accumulate in distal axons of rats
      intoxicated with p-bromophenylacetylurea (BPAU) was studied by electron
      microscopy. 35S-Methionine was injected into the ventral horn of the spinal cord
      at 2, 14, and 35 days after injection of BPAU. Three days later, samples of the
      deep peroneal nerves were obtained, and autoradiographs of thin cross sections
      were prepared. Organellar accumulations were absent from vehicle-treated control
      nerves and rare in the clinically latent period after administration of BPAU. In
      later stages of neuropathy, approximately 20% of the myelinated axons in any
      specific section were swollen and packed with tubules, membranes, and
      mitochondria. Numerous silver grains were located over the accumulated
      organelles, and the coincidence was statistically significant. The results
      indicate a sporadic local stasis of fast-transported proteins and provide a
      plausible explanation for axonal damage in BPAU neuropathy.

PMID- 1372381
TI  - Anti-HCV, anti-GOR, and autoimmunity.

PMID- 1372383
TI  - Effect of muscle stretching on the activity of neuromuscular transmission.
AB  - The purpose of this study was to investigate how muscle stretching affects the
      activity of neuromuscular transmission. The magnitude of the post-tetanic
      potentiation (PTP) of miniature end-plate potential (m.e.p.p.) frequency was
      measured in the rat soleus muscle at resting length and stretched length. The
      parameters of the magnitude of PTP can be indicators of the kinetics of Ca2+
      metabolism in the nerve terminal. One of the parameters, normalized initial post
      tetanic frequency (f), was significantly increased by stretching muscle 10% (P
      less than 0.05) and 20% (P less than 0.01) of its resting length. Another
      parameter, the time constant of augmentation (tau a), was not significantly
      changed by muscle stretching. The time constant of potentiation (tau p) was
      significantly increased by 20% muscle stretching (P less than 0.05). These
      results indicate that the Ca2+ conductance, especially the voltage-dependent Ca2+
      influx, of the nerve terminal could be increased by muscle stretching. Greater
      Ca2+ conductance of the nerve terminal would increase intracellular free Ca2+.
      Consequently, the probability of transmitter release would be increased, because
      Ca2+ is closely related to the activity of the transmitter release mechanism.

PMID- 1372382
TI  - Galanin attenuates retention of one-trial reward learning.
AB  - Galanin is a neuropeptide that coexists with acetylcholine in the
      septohippocampal pathway. Galanin appears to have a negative modulating influence
      on cholinergic transmission, suggesting that it might interfere with memory
      formation on a one-trial discriminative reward learning task. The apparatus was a
      starburst maze with five radiating alleys, one an ascending baited alley. The
      subjects were 38 two to three month old Sprague-Dawley rats cannulated in the
      body of the lateral ventricles and deprived to 80% of initial weight. Ten rats
      were infused i.c.v. over six mins. with 8 micrograms galanin in 24 microliters
      saline and 10 with saline alone. Twenty mins. after completion of infusion, each
      rat was placed in the maze and observed under "blind" conditions for number of
      errors (blind alleys entered) and latency to reach reward. Each rat's speed score
      was 100 sec./latency. One day later, each rat was retested in the maze. Each
      rat's retention scores were its decrease in errors and increase in speed between
      the single training trial and the retention trial. Galanin infused rats showed
      significantly less retention by both measures. In a second experiment, either the
      same dose of galanin or saline alone was infused 20 mins. before the retention
      trial. There was no significant effect, suggesting that galanin may interfere
      with memory formation rather than memory retrieval or task performance.

PMID- 1372384
TI  - Dextran-magnetite particles: contrast-enhanced MRI of blood-brain barrier
      disruption in a rat model.
AB  - Dextran-magnetite particles (DMP) were studied for their use as a MR contrast
      agent to visualize lesions with a blood-brain barrier (bbb) disruption. A
      freezing injury to the rat cerebral cortex was used as a model of bbb disruption.
      The biodistribution of iv-injected DMP was studied using atomic absorption
      spectrophotometry, electron microscopy, and MRI. One hour after injection, focal
      accumulation of the particles in capillary endothelial cells could be
      demonstrated in the freezing lesion. Despite the observation that the relaxivity
      of DMP in vivo appears to be less well pronounced than that in vitro, the MR
      imaging studies show that DMP can be used to visualize bbb disruption with
      adequate contrast.

PMID- 1372385
TI  - [Studies on stable control of blood sugar by continuous administration of insulin
      through isolated intestinal loop].
AB  - Insulin (INS) has been known to be absorbed through the intestine in small
      amounts and to decrease blood sugar (BS) levels. However, stable control of BS
      has not been attained by intestinal intake of INS. To elucidate the possibility
      of a surgical approach to control hyperglycemic states, Thiry-Vella loops or
      upper jejunal loop fistulae were constructed in mongrel dogs in hyperglycemic
      states. Hyperglycemic states (around 400mg/dl) were induced by injecting
      streptozotocin. Lente insulin was administered every day to control
      hyperglycemia, except for the days for studies. As we confirmed that co
      administration of aprotinin (TR) or nafamostat mesilate (FT) was necessary, to
      decrease BS by infusing INS into the intestinal loops, safe and effective dose
      levels were determined by series of preliminary infusion studies in the
      intestinal loops of diabetic dogs. By continuous infusion of these doses into the
      jejunal loop fistulae, a long term stable blood sugar control was attained in the
      diabetic dogs as long as 7 days. These results suggest that continuous infusion
      of INS with antiproteolytic adjuvants like TR or FT into the isolated small
      intestinal loop can control BS in hyperglycemic states.

PMID- 1372387
TI  - Involvement of cDNA in homologous recombination between Ty elements in
      Saccharomyces cerevisiae.
AB  - Strains carrying a marked Ty element (TyUra) in the LYS2 locus were transformed
      with plasmids bearing a differently marked Ty1 element (Ty1Neo) under the control
      of the GAL promoter. When these strains were grown in glucose, a low level of
      gene conversion events involving TyUra was detected. Upon growth on galactose an
      increase in the rate of gene conversion was seen. This homologous recombination
      is not the consequence of increased levels of transposition. When an intron
      containing fragment was inserted into Ty1Neo, some of the convertants had the
      intron removed, implying an RNA intermediate. Mutations that affect reverse
      transcriptase or reverse transcription of Ty1Neo greatly reduce the induction of
      recombination in galactose. Thus, Ty cDNA is involved in homologous gene
      conversion with chromosomal copies of Ty elements. Our results have implications
      about the way families of repeated sequences retain homogeneity throughout
      evolution.

PMID- 1372386
TI  - A collection of mRNA species that are inducible in the RAW 264.7 mouse macrophage
      cell line by gamma interferon and other agents.
AB  - To identify genes induced during macrophage activation, a cDNA library was
      prepared from cultures of the RAW 264.7 mouse macrophage cell line that had been
      treated with conditioned medium from mitogen-stimulated spleen cells, and the
      cDNA library was screened by differential plaque hybridization. Eleven cDNA
      clones, designated CRG-1 through CRG-11, corresponding to mRNA species inducible
      in RAW 264.7 cells by the spleen cell conditioned medium, were isolated.
      Inductions were not blocked by cycloheximide. All of the mRNAs were inducible by
      gamma interferon, and some were also inducible by alpha and beta interferons, by
      lipopolysaccharide, by phorbol 12-myristate 13-acetate, and by the calcium
      ionophore A23187. Sequencing of the cDNAs revealed that CRG-1, CRG-3, and CRG-5
      are cDNAs of recently identified transcription factors IRF-1, zif/268, and LRF-1
      respectively. As previously reported, CRG-2 and CRG-10 (MIG) encode new members
      of the platelet factor 4 family of cytokines. CRG-6 corresponds to a new member
      of a family of interferon-inducible genes clustered on mouse chromosome 1, CRG-9
      corresponds to a prostaglandin synthase homolog, CRG-8 corresponds to beta 2
      microglobulin, and CRG-4 corresponds to metallothionein II. CRG-11 contains
      sequences of a truncated L1Md repetitive element as well as nonrepetitive
      sequences. The nonrepetitive sequence of CRG-11 as well as the sequences of CRG-7
      are not closely related to published sequences. The CRG genes and proteins are of
      interest because of their involvement in macrophage activation, because of their
      roles as mediators of the effects of gamma interferon and other pleiotropic
      agents, and because of their usefulness as tools for studying the signal pathways
      through which gamma interferon and other inducers exert their effects on gene and
      protein expression.

PMID- 1372388
TI  - A lymphoid cell-specific nuclear factor containing c-Rel-like proteins
      preferentially interacts with interleukin-6 kappa B-related motifs whose
      activities are repressed in lymphoid cells.
AB  - The proto-oncoprotein c-Rel is a member of the nuclear factor kappa B
      transcription factor family, which includes the p50 and p65 subunits of nuclear
      factor kappa B. We show here that c-Rel binds to kappa B sites as homodimers as
      well as heterodimers with p50. These homodimers and heterodimers show distinct
      DNA-binding specificities and affinities for various kappa B motifs. In
      particular, the c-Rel homodimer has a high affinity for interleukin-6 (IL-6) and
      beta interferon kappa B sites. In spite of its association with p50 in vitro,
      however, we found a lymphoid cell-specific nuclear factor in vivo that contains c
      Rel but not p50 epitopes; this factor, termed IL-6 kappa B binding factor II,
      appears to contain the c-Rel homodimer and preferentially recognizes several IL-6
      kappa B-related kappa B motifs. Although it has been previously shown that the IL
      6 kappa B motif functions as a potent IL-1/tumor necrosis factor-responsive
      element in nonlymphoid cells, its activity was found to be repressed in lymphoid
      cells such as a Jurkat T-cell line. We also present evidence that IL-6 kappa B
      binding factor II functions as a repressor specific for IL-6 kappa B-related
      kappa B motifs in lymphoid cells.

PMID- 1372391
TI  - The neuromuscular basis of hereditary kyphoscoliosis in the mouse.
AB  - We describe a new neuromuscular disorder in the kyphoscoliotic mouse mutant (ky).
      Mice were killed at ages from birth to 210 days, and tissues were taken for
      standard light microscopy, histochemistry, nerve ending studies, and electron
      microscopy. At birth a few myofibers showed phagocytosis ultrastructurally.
      Between 6 and 25 days there was prominent necrosis and regeneration in soleus,
      gracilis, paraspinal, and back muscles. At 47 days, these muscles were atrophic
      and necrosis and regeneration were rare. At 136 days, all muscle groups,
      including head muscles, showed some degree of myofiber atrophy and gracilis was
      fibrotic. Prominent intramuscular axonal sprouting was present from 31 days.
      Peripheral nerves and anterior horn cells were normal. The findings indicate a
      neuromuscular basis of hereditary kyphoscoliosis in the mouse. The animal may be
      useful as a model of human muscle disease and scoliosis.

PMID- 1372389
TI  - Insulin is a prominent modulator of the cytokine-stimulated expression of acute
      phase plasma protein genes.
AB  - Several endocrine hormones which influence liver metabolism are known to increase
      in activity during the acute phase of injury or inflammation. We determined
      whether these hormones have the potential to influence acute-phase protein
      production in human and rat hepatoma cells. Catecholamines, glucagon, growth
      hormone, triiodothyronine, and cyclic nucleotides individually or in combination
      did not modulate the basal or the interleukin-1 (IL-1)-, IL-6-, and dexamethasone
      stimulated levels of acute-phase plasma proteins. Insulin, however, was found to
      be a rapid, nonspecific, and dose-dependent inhibitor of the cytokine and
      glucocorticoid stimulation of acute-phase protein gene expression and to exert
      its effect at the transcriptional level. The insulin inhibition applied to all
      cytokines tested but to various degrees, depending upon the particular acute
      phase gene. Insulin resulted in an early and prominent increase in the
      transcription of genes encoding the AP-1 components of JunA, JunB, and c-Fos, as
      has been observed for other growth factors. However, the effect of insulin on
      C/EBP beta was unexpected and paradoxical: while insulin completely inhibited the
      transcriptional activation of the C/EBP beta gene in cytokine- and dexamethasone
      treated cells, the level of cytoplasmic C/EBP beta RNA was elevated. Quantitation
      of C/EBP beta mRNA by Northern (RNA) blot analysis and of C/EBP beta DNA binding
      activity by Southwestern (DNA-protein) blot analysis showed that insulin, when
      combined with cytokines and dexamethasone, stimulated both the mRNA and DNA
      binding activity by a factor of 1.6 compared with that of cells treated with
      cytokines and dexamethasone alone. Transient transfection of H-35 and HepG2 cells
      with a chloramphenicol acetyltransferase (CAT) gene expression vector containing
      the C/EBP beta response element also resulted in a 1.5-fold increase of C/EBP
      beta-mediated transcription in insulin-treated cells. Transfection of CAT gene
      constructs containing increasing lengths of heptaglobin gene 5' flanking
      sequences indicated that insulin inhibition of IL-6 stimulation required the
      presence of the region from -4100 to -1030. These results suggest that insulin
      has the potential to control the transcription of acute-phase genes by at least
      two separate mechanisms.

PMID- 1372392
TI  - ATPase stain in muscle histochemistry.

PMID- 1372390
TI  - Down-regulation of cystic fibrosis transmembrane conductance regulator gene
      expression by agents that modulate intracellular divalent cations.
AB  - In cystic fibrosis (CF), epithelial cells are unable to normally up-regulate
      apical membrane Cl- secretion in response to agents which increase cyclic AMP,
      but they do increase Cl- secretion in response to increases in intracellular
      Ca2+. Since intracellular divalent cations regulate the expression of many genes,
      we hypothesized that mobilization of intracellular Ca2+ and/or other divalent
      cations might modulate not only Ca(2+)-dependent Cl- channels but also cystic
      fibrosis transmembrane conductance regulator (CFTR) gene expression. To evaluate
      this concept, HT-29 human colon carcinoma cells were cultured under various
      conditions designed to manipulate intracellular divalent cation concentrations
      and CFTR gene expression was quantified at the levels of transcription, mRNA
      accumulation, mRNA half-life, and protein. Exposure to the divalent cation
      ionophores A23187 and ionomycin (agents which increase intracellular divalent
      cation concentrations) caused dose- and time-dependent reductions of CFTR mRNA
      levels, which could be blocked by the use of Ca(2+)- and Mg(2+)-free media.
      Ionophore-induced CFTR gene modulation was also observed with T84 human colon
      carcinoma cells and freshly isolated normal human bronchial epithelial cells.
      Incubation of HT-29 cells with thapsigargin, an agent that releases Ca2+ from
      intracellular stores, or in medium containing increased extracellular
      concentrations of Ca2+ or Mg2+ also caused down-regulation of CFTR mRNA levels.
      Transcription run-on analysis showed that, parallel with the decrease in CFTR
      mRNA levels, A23187 reduced the rate of transcription of the CFTR gene, while
      CFTR mRNA transcript half-life was unaffected. Consistent with the down
      regulation of CFTR gene expression, CFTR protein levels also decreased after
      exposure to A23187. Thus, despite the independence of Ca(2+)-dependent Cl-
      channels and cyclic AMP-dependent CFTR-related Cl- channels in epithelial cells,
      increases in intracellular divalent cation concentrations down-regulate the
      expression of the CFTR gene at the transcriptional level, with consequent
      decreases in CFTR mRNA and protein.

PMID- 1372393
TI  - Cell signalling. Conviction by genetics.

PMID- 1372394
TI  - Lymphoproliferation disorder in mice explained by defects in Fas antigen that
      mediates apoptosis.
AB  - Fas antigen is a cell-surface protein that mediates apoptosis. It is expressed in
      various tissues including the thymus and has structural homology with a number of
      cell-surface receptors, including tumour necrosis factor receptor and nerve
      growth factor receptor. Mice carrying the lymphoproliferation (lpr) mutation have
      defects in the Fas antigen gene. The lpr mice develop lymphadenopathy and suffer
      from a systemic lupus erythematosus-like autoimmune disease, indicating an
      important role for Fas antigen in the negative selection of autoreactive T cells
      in the thymus.

PMID- 1372395
TI  - C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains.
AB  - The induction of the hermaphrodite vulva and the migration of the sex myoblasts
      in the nematode Caenorhabditis elegans are both controlled by intercellular
      signalling. The gonadal anchor cell induces formation of the vulva from nearby
      hypodermal cells, and a set of somatic gonadal cells attract the migrating sex
      myoblasts to their final positions. Many genes required for vulval induction have
      been identified, including the let-23 receptor tyrosine kinase gene and the let
      60 ras gene. We report here the identification and characterization of a new
      gene, sem-5 (sem, sex muscle abnormal), that acts both in vulval induction and in
      sex myoblast migration. On the basis of its DNA sequence, sem-5 encodes a novel
      228-amino-acid protein which consists almost entirely of one SH2 (SH, src
      homology region) and two SH3 domains. SH2 and SH3 domains are present in many
      signalling proteins regulated by receptor and non-receptor tyrosine kinases.
      Mutations that impair sem-5 activity alter residues that are highly conserved
      among different SH2 and SH3 domains. Our results indicate that the sem-5 gene
      encodes a novel protein that functions in at least two distinct cell-signalling
      processes.

PMID- 1372396
TI  - Code Green, Dr. Blue. Emergency paging euphemisms and the potential for
      confusion.

PMID- 1372397
TI  - Intraventricular interferon and oral inosiplex in the treatment of subacute
      sclerosing panencephalitis.
AB  - We treated 22 patients with subacute sclerosing panencephalitis (SSPE) with
      intraventricular alpha-interferon (IFN) and inosiplex PO and followed them for 2
      to 54 months. Three deaths occurred. Clinical improvement, demonstrated by
      decreasing scores on the Neurological Disability Index, occurred in 11/22 (50%);
      five patients became stable, and the progression rate of the disease decreased in
      three. The remission rate was significantly higher than untreated controls from
      the same institution. Patients who had a slowly progressive disease responded
      best to treatment. Serious side effects were rare. We recommend intraventricular
      IFN, combined with oral inosiplex, in the treatment of SSPE.

PMID- 1372398
TI  - Conjugal multiple sclerosis: immunogenetic characterization and analysis of T-
      and B-cell reactivity to myelin proteins.
AB  - We describe two families with conjugal multiple sclerosis. Onset of symptoms in
      the husbands occurred 11 and 17 years after onset of relapsing/remitting symptoms
      in their wives. There were no similarities regarding clinical manifestations of
      MS within each family. Evaluation of T-cell repertoire by enumeration of cells
      secreting interferon-gamma in response to proteolipid protein (PLP), myelin basic
      protein (MBP), and to various synthetic MBP peptides revealed similar patterns of
      T-cell reactivity within the families both in MS-affected parents and unaffected
      children. Genomic HLA-DR-DQ typing showed that T-cell reactivity was independent
      of HLA class II phenotype. Analysis of B-cell responses in blood showed low
      numbers of cells secreting IgG, IgA, or IgM antibodies against MBP, PLP, myelin
      associated glycoprotein, and myelin-oligodendrocyte glycoprotein both in MS
      affected and unaffected family members. In conclusion, our study of two families
      with conjugal MS has shown a dominant T-cell response against the same MBP
      peptide within the family both in MS-affected parents and unaffected children,
      and this T-cell response seems to be independent of the HLA class II phenotypes
      of the family members.

PMID- 1372399
TI  - Head and neck malignancies associated with HIV infection.
AB  - Immunosuppressed persons are at greater risk of developing malignancies. In human
      immunodeficiency virus (HIV) immunosuppression the most common oral cancers are
      Kaposi's sarcoma and non-Hodgkin's lymphoma. Squamous cell carcinoma has also
      been reported to be associated with HIV disease. Kaposi's sarcoma is the most
      frequent neoplastic disease in acquired immunodeficiency syndrome and is by far
      the most common in the head and neck area. This article reviews the prevalence,
      clinical features, and management of these diseases in HIV infection.

PMID- 1372400
TI  - The amino-terminal half of pp59c-fyn contains sequences necessary for formation
      of a 75 kDa form and also repressive elements absent in pp60c-src.
AB  - Members of the src family of tyrosine kinases are composed of amino acid
      sequences which can be divided into three regions: the unique amino-terminal 80
      residues; the next 180 residues of conserved but non-catalytic sequence; and the
      catalytic carboxy-terminal half of the molecule. To characterize the elements
      that regulate the catalytic and transforming activities of two members of this
      family, pp59c-fyn and pp60c-src, we generated six chimeric proteins by
      interchanging the three regions of the 531F mutant of pp59c-fyn and of the 527F
      mutant of pp60c-src. Our data indicate that substituting all or part of the amino
      terminal 263 residues of pp59c-fyn for those of 527F inhibited the kinase and
      transforming activities of 527F. Conversely, substituting the amino-terminal half
      of pp60c-src for that of 531F resulted in an increase in the transforming
      potential of 531F. These results suggest that the amino-terminal half of pp59c
      fyn contains elements which act to suppress the catalytic and transforming
      activities of the enzyme and that these suppressive elements are either absent or
      inactive in pp60c-src. These differences argue that the src family of tyrosine
      kinases are regulated differently in the cell. In vitro translation of some of
      the chimeras in rabbit reticulocyte lysates generated a 75 kDa protein in
      addition to the expected 59 kDa product. This 75 kDa species is analogous to the
      p75 protein previously detected in wild-type pp59c-fyn translation products.
      Interestingly, formation of p75 required the presence of DNA sequences encoding
      the unique amino-terminal residues of pp59c-fyn.

PMID- 1372401
TI  - Tyrosine phosphorylation of a 120,000 dalton membrane-associated protein by the
      neural form of pp60c-src, pp60c-src+.
AB  - The c-src proto-oncogene encodes a 60,000 dalton tyrosine kinase, pp60c-src,
      which is the prototype member of the family of non-receptor tyrosine kinases. A
      neural-specific form of pp60c-src, pp60c-src+, is detected only in neurons of the
      central nervous system. pp60c-src+ contains a six amino acid insert (neural
      insert) in the SH3 region that is generated by alternative splicing. Previous
      reports indicate that the profiles of proteins phosphorylated on tyrosine in
      chick embryo fibroblast (CEF) cells by pp60c-src+ or pp60c-src are equivalent. In
      this report, the activities of pp60c-src+ and pp60c-src, as well as the activated
      variants, pp60(527F+) and pp60(527F), were compared in CEF cells by examining the
      steady-state levels of tyrosine phosphorylation of several known pp60src
      substrates. Most substrates examined were phosphorylated on tyrosine to
      equivalent levels in CEF cells expressing either the neural- or fibroblast
      specific src gene products. However, the relative extent of tyrosine
      phosphorylation of a 120 kDa protein (p120) was increased in cells expressing the
      neuronal forms of either c-src or c-src527F. The increased tyrosine
      phosphorylation of p120 did not appear to be caused by the neural insert
      facilitating a specific interaction between pp60c-src+ and p120. These data
      indicate that preferential phosphorylation of p120 in neural cells may contribute
      to the specialized function of pp60c-src+ in neural cells.

PMID- 1372403
TI  - [Interferons and interferon therapy].

PMID- 1372402
TI  - Pharmacology of upper respiratory allergy.
AB  - Patients with upper respiratory allergy may benefit from the use of many
      pharmacologic products. Using the simplest form of therapy that will relieve the
      problem is usually both clinically efficacious and cost efficient. Understanding
      the indications, benefits, and potential adverse effects of each group of drugs,
      particularly the classic and new antihistamines, decongestants, intranasal and
      systemic corticosteroids, and mast cell stabilizers (such as cromolyn) will
      provide direction for the best total patient care.

PMID- 1372404
TI  - TaqI RFLP in the interferon gamma receptor 1 gene (IFNGR1) on human chromosome
      6q.

PMID- 1372405
TI  - An MspI polymorphism at the DXS11 locus.

PMID- 1372406
TI  - Two RFLPs near HOX2@/NGFR at locus D17S444E.

PMID- 1372407
TI  - Endocardial lead systems for implantable cardioverter defibrillators: uncertain
      progress beyond base camp.

PMID- 1372408
TI  - Atrial fixation leads--a visual aid confirming actual fixation.
AB  - Various active fixation mechanisms are available for atrial lead implantation.
      Confirmation of actual fixation of the lead tip in the myocardium is sometimes
      difficult with standard techniques such as fluoroscopy. Our observation of
      organized clockwise/counterclockwise motions of the fixation stylet in synchrony
      with atrial systole confirms adequate positioning of the Accufix model #330-801
      atrial lead in the right atrial appendage, which is helpful when the screw is
      difficult to visualize under fluoroscopy. This observation was confirmed in nine
      patients.

PMID- 1372409
TI  - An unusual cause of carotid sinus syndrome: multiple symmetric lipomatosis.
AB  - A 45-year-old man with multiple symmetric lipomatosis suffered recurrent syncope
      attributed to carotid sinus syndrome caused by extrinsic compression of the
      carotid body by the lipomatous masses. Surgical removal reduced but did not stop
      syncope, which was then controlled by implantation of a DDD pacemaker.

PMID- 1372410
TI  - Evaluation of electrocardiographic leads for detection of atrial activity (P
      wave) in ambulatory ECG monitoring: a pilot study.
AB  - The usual lead systems for ambulatory ECG monitoring (AECG) used in the
      evaluation of arrhythmias is a modified bipolar V-1 and V-5. A comparison of
      various lead systems to enhance the detection of atrial activity (p waves) has
      not been reported. We evaluated various surface lead systems in 12 subjects
      comparing p waves recorded at 20 mm/mV and 50 mm/sec. We compared p wave area,
      amplitude, and duration from modified bipolar V1 and V5 as well as seven
      nonstandard leads recorded on a AECG monitor. Of the seven nonstandard leads, a
      vertical sternal lead, with the negative pole just below the suprasternal notch
      and the positive pole at the xiphoid process, had the largest area (1.46 +/- 0.65
      mm2), and also had a greater area than the standard V1 (0.88 +/- 0.45 mm) and V5
      (1.06 +/- 0.49 mm2) lead system (P less than 0.01). We conclude that the bipolar
      vertical sternal lead system provides a larger p wave area than seven nonstandard
      bipolar lead systems and the two standard lead systems currently used in AECG
      monitoring. Replacement of the modified bipolar V1 lead with a vertical sternal
      lead should improve the recognition of atrial activity and, therefore, enhance
      the diagnosis of cardiac arrhythmias.

PMID- 1372411
TI  - Atrial paralysis in a patient with Emery-Dreifuss muscular dystrophy.
AB  - Emery-Dreifuss disease is a benign X-linked muscular dystrophy characterized by a
      distinct pattern of muscle weakness, which is of insidious onset and slow
      progression. It is associated with atrial paralysis that results in sudden death
      in early adulthood if left untreated. The authors report the documentation of
      electrical and mechanical silence confined to the atria in a patient with this
      disease. Electrocardiography and electrophysiological study document the absence
      of electrical atrial activity, and inability to pace the atria. Hemodynamic
      studies demonstrate the absence of A waves, and angiography revealed immobility
      of the atria. This patient has done well following the institution of permanent
      ventricular pacing. His brother, who also had muscular dystrophy, died a sudden
      cardiac death at the age of 29 after refusing medical intervention. Emery
      Dreifuss muscular dystrophy is particularly worthy of recognition because of the
      preventable occurrence of sudden death in young patients with an otherwise
      excellent prognosis. Permanent ventricular pacing is indicated.

PMID- 1372412
TI  - Survival in 1,431 pacemaker patients: prognostic factors and comparison with the
      general population.
AB  - A total of 1,431 patients (mean age 63.4 +/- 14.1) with pacemakers (96.2% VVI)
      primoimplanted between 1967 and 1985 were followed for a mean duration of 78.2 +/
      40 pacing months, with 0.6% loss to follow-up. Cumulative survival for 1, 3, and
      10 years was 0.9427, 0.9136, and 0.7536, respectively. There was no significant
      difference in survival between atrioventricular block (AVB) and sick sinus
      syndrome (SSS) patients. In addition to age and gender, factors existent prior to
      implantation that independently affected prognosis included manifest coronary
      heart disease (CHD), congenital/acquired heart lesions, heart failure, noncardiac
      internal disease, syncope, and generalized fatigue. After implantation, the most
      important factor was generalized fatigue, then age, stroke, myocardial infarct
      (MI), gender (male), heart failure, and syncope. Patients with no underlying
      disease showed an extremely high cumulative survival (0.9173 at 10 years).
      Compared to the general population of Yugoslavia, the pacemaker patients showed a
      similar yearly mortality rate until 1981. After that, elderly males (70+) had a
      significantly lower yearly mortality than the matched population. Thus, in this
      large series of pacemaker patients followed into the most recent period with an
      extremely low loss to follow-up, short- and long-term survival was very high.
      Pacemaker patients of any age who are otherwise in good health have an excellent
      prognosis.

PMID- 1372414
TI  - Is epicardial dual chamber pacing a realistic alternative to endocardial DDD
      pacing? Initial results of a prospective study.
AB  - Seventeen patients, in whom an epicardial (n = 7) or a transvenous DDDM pacemaker
      system had been implanted between June 1988 and October 1990, were followed up
      for pacemaker and lead related complications, pacemaker longevity, and
      electrophysiological lead parameters. The mean follow-up interval was 18 +/- 12
      months, maximum 34 months. There were no differences in chronic atrial and
      ventricular sensing thresholds between epicardial and endocardial stimulation,
      nor were there any differences concerning lead related complications between the
      two pacing modalities. However, atrial as well as ventricular chronic stimulation
      thresholds were significantly higher with epicardial stimulation resulting in a
      twofold increase in atrial energy consumption and a threefold increase in the
      ventricular energy consumption. Thus, in one patient with an epicardial DDD
      system, the pacemaker had to be replaced prematurely because of battery
      depletion. It is concluded that epicardial DDD stimulation can be reliably
      performed as far as atrial and ventricular sensing is concerned, but that the
      energy requirements of available myocardial leads are not satisfactory for making
      optimal use of modern pacemaker capability.

PMID- 1372413
TI  - Effects of oral propafenone therapy on chronic myocardial pacing threshold.
AB  - The effects of oral propafenone therapy on pacing threshold were studied in 36
      patients chronically paced for sick sinus syndrome or AV block. The pacemakers,
      all unipolar models and with noninvasive threshold measurement facilities, were:
      9 VVI, 15 AAI, and 12 DDD. Each patient received an initial propafenone dose of
      450 mg/day, that in 18 cases was increased to 900 mg/day. Threshold was tested at
      baseline and at each dosage after 7 days of therapy. With the lower propafenone
      dosage the threshold, measured at 2.5 V, rose from 0.14 +/- 0.10 to 0.21 +/- 0.16
      msec (+55%) in the atrium (P less than 0.0001) and from 0.10 +/- 0.08 to 0.15 +/-
      0.09 msec (+63%) in the ventricle (P less than 0.0001). In the 18 patients who
      received both dosages, the mean atrial and ventricular threshold increased from
      0.12 +/- 0.10 to 0.17 +/- 0.14 msec with the lower dose and to 0.27 +/- 0.22 msec
      (+125%) with the higher dose (P less than 0.0001 for both increments). With the
      900 mg/day dose, a threshold increment greater than or equal to 300% was observed
      in 15% of the stimulated chambers. A good linear correlation (r = 0.76) was found
      between the ventricular threshold increment and the drug induced QRS widening. In
      conclusion, treatment with oral propafenone increases atrial and ventricular
      stimulation threshold in pacemaker patients. Threshold increment is dose
      dependent and proportional to the drug induced QRS widening. In the majority of
      the cases the threshold increment is not clinically significant, but caution must
      be used in prescribing high doses of the drug to patients with high baseline
      threshold.

PMID- 1372416
TI  - A new pacemaker algorithm for continuous capture verification and automatic
      threshold determination: elimination of pacemaker afterpotential utilizing a
      triphasic charge balancing system.
AB  - A new pacemaker algorithm designed to automatically verify pacemaker capture and
      determine pacing threshold by detection of a stimulus evoked potential was
      studied in 20 patients undergoing permanent pacemaker implantation. To eliminate
      pacing stimulus afterpotential and detect an evoked response, a hardware feedback
      circuit and a software template matching algorithm were used to produce a
      triphasic charge-balanced pacing pulse. After charge balancing the pacing lead, a
      residual artifact is measured. A capture window is defined as the area integral
      of the first 24 msec of the evoked depolarization, and a capture threshold as one
      third the amplitude of the capture window. The maximum allowable residual
      artifact is one eighth the amplitude of the capture window. Once the stimulus
      afterpotential is eliminated and the evoked response detected, capture threshold
      is automatically and continuously determined and the algorithm adds a 0.8-V
      safety margin to the pacemaker output. This algorithm was run automatically and
      after simulated loss of capture, produced by manually decreasing pacer output
      below threshold, in the bipolar (13 patients) and unipolar (20 patients) pacing
      modes. In each patient loss of capture was immediately detected. The data were
      consistent (P = NS) between algorithm runs. During unipolar pacing the area
      integral of the first 24 msec of the evoked response was 412 +/- 137 versus 413
      +/- 144 and the residual artifact 5.8 +/- 4.8 versus 8.1 +/- 7.5. The resulting
      ratio (signal/noise) of the two parameters was 150 +/- 141 versus 145 +/- 181.
      Automatically determined threshold was 0.69 +/- 0.43 V versus 0.69 +/-
      0.42.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372415
TI  - Effects of verapamil on ventricular tachycardia induced by ouabain in guinea
      pigs.
AB  - Calcium ions appear to play a central role in the development of ventricular
      arrhythmias associated with digitalis intoxication. Therefore, the effects of the
      calcium channel antagonist, verapamil, on ouabain-induced ventricular tachycardia
      were investigated. Ventricular tachycardia (three or more consecutive wide QRS
      complexes) was induced in guinea pigs by intravenous infusion of ouabain (1
      microgram/min) and bursts of rapid ventricular stimulation. Of seven guinea pigs
      given the infusion of ouabain, all developed ventricular tachycardia at a dose of
      82 +/- 17 micrograms/kg (mean +/- SD) and none developed heart block or asystole.
      Eight guinea pigs were treated with verapamil (2 micrograms/min for 30 minutes)
      prior to exposure to ouabain. Of those eight animals, only two developed
      ventricular tachycardia but six developed heart block or asystole at a
      significantly higher dose of ouabain (154 +/- 47 micrograms/kg). None of three
      control guinea pigs given an infusion of normal saline for 90 minutes developed
      ventricular tachycardia. These results show that pretreatment with verapamil
      inhibits ouabain-induced ventricular tachycardia in guinea pigs. Combined
      treatment with verapamil and ouabain is associated with a high incidence of heart
      block and asystole, which may limit the usefulness of verapamil.

PMID- 1372417
TI  - Long-term therapy of antitachycardia pacing for supraventricular tachycardia.
AB  - Long-term antitachycardia pacing therapy with the InterTach 262-12 and 262-16 was
      evaluated in 32 consecutive patients (mean age 50 +/- 13 years) with recurrent,
      drug refractory supraventricular tachycardia. AV nodal reentrant tachycardia was
      present in 20 patients, Wolff-Parkinson-White syndrome in ten patients, and a
      reentrant tachycardia due to Mahaim fibers in one patient. During follow-up of 39
      +/- 17 months, 250 persistent tachycardia episodes occurred in 22 patients. By
      adjusting detection and termination mode, recurrent supraventricular tachycardia
      could be controlled in 19 of 32 patients (60%) by antitachycardia pacing alone.
      Concomitant antiarrhythmic drug therapy was required in ten of 32 patients (30%).
      During follow-up antitachycardia pacing became ineffective in three patients
      (10%). Thus, chronic antitachycardia pacing proved to be safe and effective in
      selected patients with drug refractory supraventricular tachycardia and could
      significantly improve quality of life by rapid termination of recurrent
      supraventricular tachycardia episodes.

PMID- 1372418
TI  - Activity-based pacing: comparison of a device using an accelerometer versus a
      piezoelectric crystal.
AB  - The EXCEL VR, an accelerometer-based pacemaker (AC), and the Legend, a pacemaker
      utilizing a piezoelectric crystal (PZ), were compared under ergometric conditions
      and during stair climbing to assess the appropriateness of their rate responses.
      The pacemakers, programmed to the manufacturers' nominal settings in order to
      compare different technologically based sensors under identical conditions, were
      strapped over subjects' left mid-pectoral region. Placement of the devices was
      randomized to control for positional effects. Ten healthy subjects (55-72 years)
      completed a graded exercise treadmill test to 80% of maximum predicted heart rate
      (HR). An additional group of ten subjects (50-66 years) completed exercise
      protocols involving bicycle ergometry and stair climbing. Throughout all tests,
      pacemaker pulse rates and subjects' intrinsic HR were monitored continuously. For
      the treadmill exercise, the average correlations between the AC and PZ
      pacemakers' pulse rate and HR for the group as a whole were r = 0.92 and r =
      0.82, respectively. Individual subject comparisons were also made between each
      pacemaker rate and intrinsic HR. The mean difference from intrinsic rate was 11
      ppm for the AC pacemaker and 24 ppm for the PZ pacemaker. In addition, the PZ
      pacemaker's maximal pulse rate was significantly lower (105 +/- 9.6 ppm) than the
      other two rates (AC 137 +/- 6 ppm; intrinsic HR 129 +/- 2 beats/min). Throughout
      the bicycle ergometry testing, the intrinsic HR was higher than the AC and PZ
      pacing rates. However, the AC's rate was significantly higher than the PZ's rate.
      When subjects ascended stairs, the intrinsic HR and AC rate were closely
      correlated, but the PZ rate was significantly lower.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1372419
TI  - Propagation versus delayed activation during field stimulation of cardiac muscle.
AB  - This modeling study seeks to explain the experimentally detected delay between
      the application of an electric field and the recorded response of the
      transmembrane potential. In this experiment, conditions were deliberately set so
      that the field should excite all cells at once and so that no delay should be
      caused by a propagating wave front. The explanation of the observed delay may lie
      in the intrinsic properties of the membrane. To test this hypothesis, the
      strength latency curves were determined for three cases: (1) for a membrane patch
      model, in which the membrane is uniformly polarized and its intrinsic properties
      can be studied; (2) for the cardiac strand directly excited by the electric
      field; and (3) for the cardiac strand excited by a propagating wave front. The
      models of the membrane patch and the directly excited strand yield excitation
      delays that are comparable to those observed experimentally in magnitude and in
      the overall shape of the strength latency curves. The delays resulting from
      propagation are, in general, dependent on the position along the strand, although
      for some positions the strength latency curves for propagation are similar to
      those obtained from the directly activated strand and from the patch model.
      Therefore, the delay in excitation does not necessarily imply the presence of
      propagating wave fronts and can be attributed to intrinsic membrane kinetics.

PMID- 1372420
TI  - First derivative of right ventricular pressure, dP/dt, as a sensor for a rate
      adaptive VVI pacemaker: initial experience.
AB  - Ten patients underwent implantation of a rate adaptive ventricular pacing system
      with a new pulse generator and lead. The unipolar lead has a steroid eluting tip
      and a pressure sensor. The first derivative of the signal from this sensor,
      dP/dt, is determined and the pacemaker rate is varied in response to changes in
      the right ventricular dP/dtMAX. During implantation, dP/dt values were in the
      range of 180-720 mm Hg/sec. The autothreshold for pacing at 2.5 V remained
      unchanged 1 month after implantation (0.065 +/- 0.045 msec, range 0.05-2.00 msec)
      and only slightly increased after 3 months (0.075 +/- 0.045 msec, range 0.05-2.00
      msec). A significant correlation existed between the dP/dt measured during
      implantation and the right ventricular pressure measured by telemetry at follow
      up visits (r = 0.93, P = 0.0001). Initial pacemaker programming was performed on
      the second day after implantation following a short walk and was adjusted
      subsequent to follow-up visits according to the patient's subjective assessment
      and in accordance with the results of exercise tests and Holter monitoring.
      Exercise and Holter tests did not significantly change initial programming. There
      was a significant correlation between right ventricular systolic pressure and the
      rate response setting (r = -0.66, P less than 0.05). During dP/dt pacing, all
      patients felt well, and eight of these reported an improvement compared to
      nonrate adaptive pacing. The heart rate response to effort and recovery was
      appropriate. It was concluded that: (1) right ventricular dP/dt is a suitable
      parameter for controlling the pacing rate; (2) appropriate programming of the
      dP/dt pacemaker results in a suitable heart rate response to exercise and
      recovery.

PMID- 1372421
TI  - Development of a rate adaptive pacemaker based on the maximum rate-of-rise of
      right ventricular pressure (RV dP/dtmax).
AB  - The maximum rate of rise of right ventricular pressure (RV dP/dtmax) may change
      in response to physiological stress and thereby provide an appropriate parameter
      upon which to base rate adaptive pacing. Initial feasibility testing was carried
      out in six patients using externally closed loop rate adaptive pacing with a
      pressure sensing lead (Model 6220) and an investigational VVI pulse generator
      (Medtronic, Model 2451). During exercise, maximum positive RV dP/dtmax increased
      from 223 +/- 55 to 405 +/- 181 mmHg.sec.1 (P less than 0.05). Based on these
      results, rate adaptive pulse generators using maximum positive RV dP/dt were
      implanted in 12 patients (Medtronic, Model 2503). Exercise treadmill testing in
      the VVI mode resulted in heart rates ranging from 69 +/- 6 beats/min at rest to
      79 +/- 14 beats/min (n = 12; P greater than 0.05). In contrast, VVIR mode pacing
      rates ranged from 71 +/- 11 beats/min to 115 +/- 24 beats/min (n = 17; P less
      than 0.05). Holter recording showed heart rates ranging from 51 +/- 6 to 110 +/-
      22 beats/min during activities of normal daily living (n = 9; P less than 0.05).
      Passive postural tilt resulted in rates of 69 +/- 8 beats/min in the supine
      position increasing to 74 +/- 14 beats/min with 60 degrees upright tilt (n = 16;
      P greater than 0.05). With up to 5-year follow-up data, there have been no late
      failures of pacing but one lead showed insulation failure with over- and
      undersensing after 4.5 years. A number of deficiencies were identified in the
      prototypes leading to modifications of a subsequent generation of rate responsive
      pacemaker based on RV dP/dtmax. These initial data demonstrate that rate adaptive
      pacing based on RV dP/dtmax responds in a physiological manner. This rate
      responsive system is of particular interest as it is based on a beat-to-beat
      parameter of cardiac mechanical function.

PMID- 1372423
TI  - Use of transesophageal echocardiography (TEE) aided radiofrequency ablation of
      Wolff-Parkinson-White accessory pathways.

PMID- 1372424
TI  - Fusion or confusion on Holter recording.

PMID- 1372422
TI  - Effect of vagal nerve electrostimulation on the power spectrum of heart rate
      variability in man.
AB  - The power spectrum of heart rate variability contains low frequency (LF = 0.08
      0.12 Hz) and high frequency (HF = 0.18-0.30 Hz) components said to represent
      neurocardiac rhythms. To verify whether such a relationship exists we report a
      unique study where the heart rate autospectrum was determined in a 28-year-old
      epileptic male patient with an implanted vagal electrical stimulator. The
      stimulator was activated at 20 Hz, 300 microseconds pulse, and 1.25 V. Continuous
      ECG and respiratory waveform records were obtained over 45 minutes every 8 hours
      (7-8 AM; 3-4 PM; 11-12 PM) with the stimulator ON, then 24 hours OFF and then 24
      hours ON again. The overall LF:HF peak ratio increased from 0.64 to 1.99 (P less
      than 0.001) after the stimulator was turned OFF. There was a dramatic increase in
      the LF peak power (greater than 60%) and a corresponding decrease in the HF peak
      power (greater than 65%) when the stimulator was turned OFF. These values were
      reversed when the stimulator was turned ON again. In the early morning and late
      evening hours, there was a significant rightward shift in the LF peak power
      frequency (average 0.057 to 0.075 Hz) whenever the stimulator was ON. Otherwise,
      there were no significant circadian variations in any of the autospectral
      components. The results demonstrate an unequivocal relationship between selective
      vagal nerve electrostimulation and alterations in the heart rate autospectrum.

PMID- 1372425
TI  - Evaluation of very rapid emit Qst methods for measuring serum procainamide and N
      acetylprocainamide concentrations.
AB  - This study assessed the Emit Qst procainamide (PA) and N-acetylprocainamide
      (NAPA) assays. Accuracy and intraday precision were evaluated by repeatedly
      measuring PA and NAPA concentrations in spiked serum samples using Qst and high
      performance liquid chromatography methods. Interday precision was evaluated by
      measuring concentrations in spiked samples over 4 weeks. Correlation between
      methods was assessed in patient samples, and proportional, constant, and random
      errors were estimated. Intraday coefficients of variation (CVs) were below 6.4%
      for PA and NAPA for both methods; interday CVs were below 7.8%. The proportional,
      constant, and random errors of the PA Qst assay in patient samples were 5.7%, 
      0.224 mg/L, and +/- 0.574 mg/L, respectively. The same errors in the NAPA Qst
      assay were 17.2%, 0.229 mg/L, and +/- 1.79 mg/L, respectively. The Qst assays are
      rapid, accurate, and precise methods for routine clinical measurement of PA and
      NAPA, although the proportional error in the NAPA assay should be recognized.

PMID- 1372426
TI  - Prostate specific antigen and prostatitis. I. Effect of prostatitis on serum PSA
      in the human and nonhuman primate.
AB  - Prostate specific antigen (PSA) has become a mainstay in the diagnosis and
      management of patients with prostate cancer. We have found, as have others, that
      it may be elevated in patients with prostatic inflammation. Ten patients had
      clinical evidence of prostatitis and elevated PSA levels. Six of these had
      persistently elevated levels after antibiotic treatment. After transrectal
      ultrasonography and biopsy, two had findings of adenocarcinoma, and the rest had
      a pathologic diagnosis of acute or chronic prostatitis. We studied this process
      in an experimental model of prostatitis using a nonhuman primate. We infected six
      cynomolgus monkeys and followed their PSA levels until resolution of the
      infection. The PSA peaked between 5 and 7 days after inoculation and gradually
      returned to baseline in 8 weeks. The dramatically elevated serum PSA levels in
      bacterial prostatitis can cause confusion in the diagnosis of prostatic
      carcinoma.

PMID- 1372427
TI  - Prostate specific antigen and prostatitis. II. PSA production and release
      kinetics in vitro.
AB  - Elevations in serum prostate specific antigen (PSA) levels in patients with
      prostatitis are well known, but the pathophysiologic mechanisms involved with
      this phenomenon are poorly understood. We have recently evaluated the effect of
      prostatitis on PSA levels in primates. This data demonstrated a rapid rise in
      PSA, which subsequently fell along the biological decay curve. This suggested a
      release of sequestered PSA. We evaluated the effect of infection upon PSA
      production for the prostatic adenocarcinoma cell line LNCaP. The cell line was
      determined to produce 9.6 +/- 2.7 fg/cell/hr PSA with essentially linear
      kinetics. No effect was seen with dead bacteria, bacterial supernatant or
      complement upon the PSA production. Live E. coli had no effect for 4-8 hours at
      which time the cells sloughed and PSA production ceased. No release of stored PSA
      was seen. These data do not elucidate the reasons for increased serum PSA levels
      found with acute bacterial prostatitis, but indicate that it is not a storage
      phenomenon.

PMID- 1372428
TI  - Evaluation of a new tumor marker for localized prostate cancer.
AB  - Adenocarcinoma associated antigen (ACAA) is a large molecular weight protein that
      is normally found in low serum levels. Recent data have revealed elevations in
      patients with adenocarcinomas, including prostate cancer. To evaluate the
      relationship of ACAA levels with prostate cancer, we measured the cytosol content
      in malignant and nonmalignant prostate tissue and compared these results to those
      of the standard markers, prostatic acid phosphatase (PAP) and prostatic specific
      antigen (PSA). Enzyme solid phase immunoassay was used to quantitate PSA and ACAA
      levels, and the enzymatic method was used to measure PAP. Wedge resection from
      the right and left posterior lobes of 50 fresh radical retropubic prostatectomy
      specimens were used for cytosol analysis. All foci of within each prostate gland
      were carefully mapped by a single pathologist. When all malignant wedges (N = 74)
      were compared to all the benign wedges (N = 21), only the PSA levels showed
      significant elevation (p less than 0.02). However, when benign and malignant
      tissue from the same prostate were available for comparison, both PSA (N = 17)
      and ACAA (N = 16) showed significant elevations in the cytosol of the malignant
      tissue (p less than 0.002 and p less than 0.03, respectively). Although not
      statistically significant, the cytosol PAP did show a consistent trend to be
      greater in malignant tissue. It appears that there is an association of increased
      cytosol ACAA and PSA with prostate cancer.

PMID- 1372430
TI  - The relative efficacy of terazosin versus terazosin and flutamide for the
      treatment of symptomatic BPH.
AB  - Pharmacotherapy for the treatment of BPH is currently being targeted to relax
      prostate smooth muscle (alpha blockade) and decrease prostate volume (androgen
      suppression). The objective of the present study was to determine the relative
      efficacy of terazosin vs. terazosin and flutamide (combination therapy) for the
      treatment of symptomatic BPH. Twenty-nine males with symptomatic BPH were
      enrolled into this 6-month open label study. The entry criteria included peak
      urinary flow rate between 4-15 ml/sec, a total Boyarsky symptom score greater
      than 7, and postvoid residual less than 300 ml. The daily dosage of terazosin was
      titrated to 5 mg over a 2-week interval. A 750 mg daily dosage of flutamide was
      added following 1 month of terazosin monotherapy. The dosages were lowered if
      significant adverse events developed. Efficacy assessments were performed at 1
      month (terazosin alone), 6 months (combination therapy), or at the time of early
      withdrawal from the study. The efficacy of combination therapy was evaluable in
      24 patients receiving combination therapy. At one month, the mean peak urinary
      flow rate and mean total Boyarsky symptom score improved 38% and 56% relative to
      baseline, respectively. The present study confirmed the previously observed
      efficacy and safety of terazosin for BPH. The addition of flutamide did not
      result in statistically significant improvements in the peak urinary flow rate or
      total Boyarsky symptom score. The adverse events related to flutamide resulted in
      16 dose reductions and 14 premature withdrawals. The role of combination therapy
      will require a randomized placebo controlled study sufficiently powerful to
      identify clinically and statistically significant improvements in objective
      outcome parameters relative to the monotherapies.

PMID- 1372429
TI  - Studies on the proliferation, secretory activities, and epidermal growth factor
      receptor expression in benign prostatic hyperplasia explant cultures.
AB  - Short term explant cultures of benign prostatic hyperplasia (BPH) tissues were
      studied immunohistochemically to characterise both the morphological changes
      within the explant tissue and the cellular origin of the epithelial cell
      outgrowth. Altered patterns of expression of cytokeratins, prostate specific
      antigen (PSA) prostatic acid phosphatase (PAP), and epidermal growth factor (EGF)
      receptor were observed. After sloughing of the secretory epithelium in the
      majority of the acini repopulation and outgrowth of a monolayer was accomplished
      by cells which were strongly positive for stratifying keratin and EGF receptor
      and negative for PAP and PSA, indicative of a basal cell phenotype. The peak of
      proliferation in the acini, as assessed by Ki-67 immunohistochemistry, occurred
      after 2-4 days in culture. Preliminary studies on BPH tissue xenografts in nude
      mice indicated that better preservation of normal morphology, secretory activity,
      and antigen expression could be achieved.

PMID- 1372431
TI  - Temperature mapping in the canine prostate during transurethrally-applied local
      microwave hyperthermia.
AB  - Although the therapeutic effects of heat on tumors have been known for more than
      a century, only recently has hyperthermia been applied in the treatment of
      various solid tumors in a scientific fashion. In preliminary clinical trials,
      heat applied by transurethrally or transrectally placed microwave antennas has
      been used in the treatment of benign prostatic hyperplasia (BPH) with some
      success. However, basic information about prostatic temperature distribution and
      the cellular effects of hyperthermia is lacking. In an attempt to establish the
      safety of local hyperthermia of the prostate and the precise temperature
      distribution within the gland, we performed temperature mapping studies in canine
      prostates. Eight mongrel dogs were anesthetized, and a 16 Fr catheter with three
      helical coil microwave antennas was placed in the bladder through a perineal
      urethrostomy. Laparotomy was performed and the bladder opened. The antennas were
      placed under direct control in the prostatic urethra. Linear array and single
      point thermometers (Clini-Therm TS1200 thermometry system) were placed (1) within
      the catheter alongside the antennas, (2) alongside the Foley catheter in the
      urethra, and (3) longitudinally and radially in the prostate for mapping of
      tissue temperature. Heating was performed with a 915-MHz ISM frequency Z-80
      microprocessor controlled microwave power generator (Prostek 3000, Clini-Therm
      Corporation, Dallas, TX) using 2-9 watts per channel (6-27 watts total) for 30
      min to 1 hr. Baseline body temperatures varied between the individual dogs from
      37 degrees to 38 degrees C, but temperature distribution within the prostate was
      even prior to heating. With relatively low power (6 watts total), temperatures of
      greater than or equal to 45 degrees C were reached within the catheter.
      Therapeutic temperatures of approximately 43 degrees C were achieved in the
      periurethral prostate. Intraurethral temperatures were in general 1-2 degrees C
      lower than within the catheter. The radial temperature dropoff in the prostate
      was sharp and about 1 degrees C per 3-mm distance from the catheter. This would
      limit the area of effectiveness to a periurethral zone of 1 cm in diameter in
      this model. No unsafe temperature peaks were noted either intraurethrally or
      between the prostate and the rectum during steady-state conditions. Histologic
      studies demonstrated an intact rectal wall and varying degrees of prostatic
      inflammation and/or necrosis despite uniform treatment regimens administered.
      These studies demonstrate the short-term safety of microwave hyperthermia in the
      canine prostate. Further studies will be necessary to determine the clinical
      efficacy and toxicity in men with BPH.

PMID- 1372432
TI  - [Exogenous allergic alveolitis: assessment of antigen-specific IgG antibodies
      using a new chemiluminescence method].
AB  - The demonstration of elevated levels of antigen-specific IgG antibodies is of
      importance for the diagnostic workup of patients with a suspected
      hypersensitivity pneumonitis. We established a solid phase immunoassay for the
      determination of these antibodies based on chemiluminescence (CLIA). The CLIA
      demonstrated a low level of unspecific binding. The reproducibility of the CLIA
      was evaluated by calculating the intra- and inter-variation; the variation
      coefficient was 4% (intra-variation) resp. 13% (inter-variation). Using the CLIA
      we quantified IgG antibodies against Aspergillus fumigatus (A.f.), Micropolyspora
      faeni (M.f.) and Thermoactinomyces vulgaris (T. v.) in the sera of patients with
      farmer's lung (FL, n = 10), healthy farmers (n = 13) and normal volunteers
      without prior hay contact (n = 12). For all 3 antigens the antibody levels of
      patients with FL were significantly higher than the titers of the other groups.
      As a comparison all sera were tested with an established solid phase
      radioimmunoassay (RIA). Using the RIA a statistically significant difference
      could only be demonstrated between the antibody levels of patients with FL and of
      normal volunteers without prior hay contact and was limited to the antigens A.f.
      and M.f. Comparing the results achieved with both assays on a point by point
      basis there was a good correlation for the antigens A.f. (r = 0.69; p less than
      0.0001) and M.f. (r = 0.74; p less than 0.0001), whereas the correlation for T.v.
      was not satisfying (r = 0.42, p less than 0.02). In summary the CLIA is a
      promising new method for the determination of antigen specific IgG antibodies
      with the advantages of a radioimmunoassay without its potential hazards.

PMID- 1372433
TI  - Induction of nitric oxide synthase activity by toxic shock syndrome toxin 1 in a
      macrophage-monocyte cell line.
AB  - Toxic shock syndrome toxin 1 (TSST-1) is a Mr 22,000 protein produced by
      Staphylococcus aureus. It is thought to be the cause of toxic shock syndrome. We
      investigated the hypothesis that TSST-1 induces nitric oxide (NO) synthase and
      that the NO formed may be involved in the pathogenesis of toxic shock syndrome.
      We used the murine monocyte-macrophage cell line J744.2 that responds to TSST-1
      and also expresses NO synthase activity upon immunological stimulation. J774.2
      macrophages stimulated with TSST-1 (10-100 nM) generated nitrite, a breakdown
      product of NO, and induced concentration-dependent elevations of cGMP in the pig
      kidney epithelial cell line (LLC-PK1). This latter effect was due to the
      generation of L-arginine-derived NO for it was (i) abolished by oxyhemoglobin (10
      microM), a scavenger of NO, or by methylene blue (10 microM), an inhibitor of NO
      activated guanylate cyclase; (ii) potentiated by superoxide dismutase (100
      units/ml), which prolongs the life of NO; (iii) inhibited by NG-monomethyl-L
      arginine (0.3 mM), an inhibitor of NO synthase; (iv) significantly decreased when
      L-arginine (0.4 mM) in the medium was replaced by D-arginine (0.4 mM). Moreover,
      TSST-1 (100 nM) enhanced the activity of cytosolic NO synthase in J774.2 cells.
      Hydrocortisone (1 microM) but not indomethacin (5 micrograms/ml) or salicylic
      acid (5 micrograms/ml) prevented the generation of NO2- and the increases in cGMP
      levels in LLC-PK1 cells induced by J774.2 cells stimulated with TSST-1. The
      effects of hydrocortisone were partially reversed by coincubation with RU 486 (1
      microM), an antagonist of glucocorticoid receptors. Thus, TSST-1 and perhaps
      other exotoxins produced by Gram-positive bacteria induce NO synthase and the
      increased NO formation may contribute to toxic shock syndrome and possibly to
      changes in the immune responses that accompany infection.

PMID- 1372434
TI  - Activation of the cytotactin promoter by the homeobox-containing gene Evx-1.
AB  - Cytotactin is a morphoregulatory molecule of the extracellular matrix affecting
      cell shape, division, and migration that appears in a characteristic and complex
      site-restricted pattern during embryogenesis. The promoter region of the gene
      that encodes chicken cytotactin contains a variety of potential regulatory
      sequences. These include putative binding sites for homeodomain proteins and a
      phorbol 12-O-tetradecanoate 13-acetate response element (TRE)/AP-1 element, a
      potential target for transcription factors thought to be involved in growth
      factor signal transduction. To determine the effects of homeobox-containing genes
      on cytotactin promoter activity, we conducted a series of cotransfection
      experiments on NIH 3T3 cells using cytotactin promoter-chloramphenicol
      acetyltransferase (CAT) reporter gene constructs and plasmids driving the
      expression of mouse homeobox genes Evx-1 and Hox-1.3. cotransfection with Evx-1
      stimulated cytotactin promoter activity whereas cotransfection in control
      experiments with Hox-1.3 had no effect. To localize the sequences required for
      Evx-1 activation, we tested a series of deletions in the cytotactin promoter. An
      89-base-pair region containing a consensus TRE/AP-1 element was found to be
      required for activation. An oligonucleotide segment containing this TRE/AP-1 site
      was found to confer Evx-1 inducibility on a simian virus 40 minimal promoter;
      mutation of the TRE/AP-1 site abolished this activity. To explore the potential
      role of growth factors in cytotactin promoter activation, chicken embryo
      fibroblasts, which are known to synthesize cytotactin, were first transfected
      with cytotactin promoter constructs and cultured under minimal conditions in 1%
      fetal bovine serum. Although the cells exhibited only low levels of CAT activity
      under these conditions, cells exposed for 12 h to 10% (vol/vol) fetal bovine
      serum showed a marked increase in CAT activity. Cotransfection with Evx-1 and
      cytotactin promoter constructs of cells cultured in 1% fetal bovine serum was
      sufficient, however, to produce high levels of CAT activity. These findings are
      consistent with the hypothesis that Evx-1, a homeobox-containing gene, may
      activate the cytotactin promoter by a mechanism involving a growth-factor signal
      transduction pathway. More generally, the results support the hypothesis that the
      place-dependent expression of morphoregulatory molecules may depend upon local
      cues provided by homeobox genes and their encoded proteins.

PMID- 1372435
TI  - cDNA cloning of a liver isoform of the phosphorylase kinase alpha subunit and
      mapping of the gene to Xp22.2-p22.1, the region of human X-linked liver
      glycogenosis.
AB  - We have cloned cDNA molecules encoding another isoform of the alpha subunit of
      phosphorylase kinase (ATP:phosphorylase-b phosphotransferase, EC 2.7.1.38).
      Sequence comparison with the previously characterized muscle isoform reveals a
      pattern of highly conserved and variable domains and demonstrates that the
      isoforms are the products of distinct genes. In contrast to the muscle isoform
      gene, PHKA1, the gene of this additional isoform, PHKA2, is predominantly
      expressed in liver and other nonmuscle tissues. It was mapped to the distal short
      arm of the human X chromosome (Xp22.2-p22.1), the same region to which human X
      linked liver glycogenosis due to phosphorylase kinase deficiency has been mapped.
      Thus, X-linked liver glycogenosis is probably caused by mutations affecting
      PHKA2.

PMID- 1372436
TI  - Paradoxical transcriptional activation of rat liver cytochrome P-450 3A1 by
      dexamethasone and the antiglucocorticoid pregnenolone 16 alpha-carbonitrile:
      analysis by transient transfection into primary monolayer cultures of adult rat
      hepatocytes.
AB  - The family 3A cytochromes P-450, among the most abundant members of this
      supergene family of microsomal hemoproteins expressed in animal and human liver,
      are inducible by glucocorticoids but also by such antiglucocorticoids as
      pregnenolone 16 alpha-carbonitrile (PCN). To investigate the mechanism for this
      nonclassical glucocorticoid effect, we analyzed the ability of 1.5 kilobases of
      DNA or of its successive subsegments isolated from the 5' flanking region of the
      rat CYP3A1 structural gene to modulate transcription of a reporter gene
      consisting of a viral promoter coupled to the chloramphenicol acetyltransferase
      (CAT) structural gene (expression vector pBLCAT2) and transiently expressed in a
      homologous cell system consisting of primary monolayer cultures of adult rat
      hepatocytes in which CYP3A1 mRNA and protein are inducible. The CAT activity
      measured after chimeric gene constructions were transferred into the cultured rat
      hepatocytes by lipofection increased as much as 7.2-fold if the cells were
      treated with dexamethasone (DEX). One CYP3A1 fragment (positions -220 to -56; 164
      base pairs), which does not contain a traditional glucocorticoid responsive
      element, conferred dose-dependent DEX responsiveness independent of its
      orientation but not its position in pBLCAT2. This construction was activated by
      addition of PCN to the cultures and was synergistically induced by PCN plus DEX.
      In contrast, induction of CAT activity in cultures containing MMTVCAT, a plasmid
      containing the CAT gene controlled by the mouse mammary tumor virus long terminal
      repeat, was unaffected by PCN treatment, required lower concentrations of DEX for
      a maximal response, and was inhibited by treatment with DEX plus PCN. We conclude
      that a primary mechanism for induction of CYP3A1 is stimulated transcription
      through a pathway activated by steroid hormones.

PMID- 1372437
TI  - Molecular cloning and expression of chicken C-terminal Src kinase: lack of stable
      association with c-Src protein.
AB  - Cloning and sequencing of chicken C-terminal Src kinase (CSK), a tyrosine kinase
      that phosphorylates the regulatory C-terminal tyrosine residue present on
      cytoplasmic tyrosine kinases of the Src family, demonstrated a high degree of
      interspecies conservation as well as src homology 2 and 3 domains N-terminal to
      the kinase domain. The lack of autophosphorylation sites distinguishes CSK from
      other tyrosine kinases. CSK is unique and does not belong to a gene family,
      suggesting that it may phosphorylate other members of the Src family of tyrosine
      kinases in addition to c-Src. Since complex formation between c-Src and CSK
      seemed a likely regulatory step in the control of c-Src kinase activity, such an
      association was investigated by immunoprecipitation and Western blotting as well
      as intracellular localization studies. Although some portions of CSK were found
      in a membrane fraction, no complex formation between CSK and c-Src was observed,
      suggesting that the src homology 2 domain of CSK does not play a role in the
      direct interaction of c-Src.

PMID- 1372438
TI  - Chromosomal position of rearranging gene segments influences allelic exclusion in
      transgenic mice.
AB  - Formation of a complete immunoglobulin heavy-chain transcription unit involves
      the ordered rearrangement of variable (V), diversity (D), and joining (J) region
      gene segments. In antibody-producing cells, this process is regulated such that
      only one of two antibody genes is expressed. Experiments with transgenic mice
      suggest that this mechanism, known as allelic exclusion, is mediated through the
      membrane-bound form of the immunoglobulin heavy chain. However, in all transgenic
      lines produced to date exclusion of the endogenous genes by the transgene is
      incomplete. To characterize the molecular basis for this escape from regulation,
      we have examined the rearrangements of endogenous immunoglobulin heavy-chain
      genes. We find that a transgene that encodes the membrane-bound form of human IgM
      efficiently inhibits rearrangements of endogenous gene segments located at the 5'
      end of the heavy-chain locus. However, recombining elements found at the 3' end
      of the locus escape and continue to undergo recombination. A transgene that
      encodes the secreted form of the same immunoglobulin protein has no effect on
      recombination, regardless of position of the recombining segment in the
      chromosome. These results have important implications for our understanding of
      the control of allelic exclusion.

PMID- 1372439
TI  - Granule membrane protein 140 (GMP140) binds to carcinomas and carcinoma-derived
      cell lines.
AB  - The glycoproteins granule membrane protein 140 (GMP140), endothelial-leukocyte
      adhesion molecule 1 (ELAM-1), and Leu-8 are members of a family of glycoprotein
      receptors (selectins or LEC-CAMs) that play an important role in adhesive
      interactions between circulating leukocytes and vascular endothelium. Recently it
      has been reported that ELAM-1 is able to mediate the binding of the colon
      carcinoma cell line HT-29 to cytokine-activated vascular endothelium, suggesting
      that tumor cell adhesion to vascular endothelium, a prerequisite for tumor
      extravasation and metastasis, is in part the result of adhesive interactions
      between blood-borne tumor cells and cell surface proteins expressed by vascular
      endothelium. Here, using an approach in which soluble immunoglobulin chimeras of
      the GMP140 and ELAM-1 receptors were prepared and used to carry out
      immunohistological studies, we establish that GMP140 binds to tumor cells in a
      variety of human carcinoma tissue sections (colon, lung, and breast), whereas
      ELAM-1 binds exclusively to tumor cells in colon carcinoma tissue sections. In
      addition, GMP140 was found to bind to the cell surface of a number of cell lines
      derived from various carcinomas but not from melanomas, whereas ELAM-1 bound only
      colon carcinoma cell lines. We further investigated the nature of the ligands of
      GMP140 and ELAM-1 on the surface of the carcinoma cells and found that the GMP140
      ligand on the surface of tumor cells appears to be distinct from that expressed
      on the myeloid cell line HL-60. Neuraminidase treatment of a breast carcinoma
      cell line does not affect, or in some instances increases, GMP140 binding,
      whereas it completely abolishes GMP140 binding to HL-60 cells. On the other hand,
      the ligand of ELAM-1 on both the colon carcinoma and HL-60 cells is neuraminidase
      sensitive in accord with its identification as sialyl-CD15. Parallel results were
      obtained with neuraminidase-treated frozen carcinoma tissue sections. The present
      findings form the basis for investigating the role of GMP140 in tumor
      invasiveness and metastasis.

PMID- 1372440
TI  - Isolation and characterization of human cDNA clones encoding a high mobility
      group box protein that recognizes structural distortions to DNA caused by binding
      of the anticancer agent cisplatin.
AB  - Human cDNA clones encoding a structure-specific recognition protein, SSRP1, that
      binds specifically to DNA modified with cisplatin have been isolated and
      characterized. The SSRP1 gene maps to human chromosome 11q12. The cDNA clones,
      obtained by using partial-length cDNAs described previously, predict an 81-kDa
      protein containing several highly charged domains and a stretch of 75 amino acids
      47% identical to a portion of the high mobility group (HMG) protein HMG1. This
      HMG box most likely constitutes the structure recognition element for cisplatin
      modified DNA, with the probable recognition motif being the local duplex
      unwinding and bending toward the major groove that occurs upon formation of
      intrastrand cis-[Pt(NH3)2]2+ d(GpG) and d(ApG) cross-links. Although the DNA
      recognition properties of members of the HMG-box family of proteins have been
      characterized with respect to their sequence specificity, the present work
      demonstrates that proteins with this domain can recognize particular DNA
      structures as well. The Pt-DNA SSRP described here is the human homolog of a
      recently identified mouse protein that binds to recombination signal sequences
      [Shirakata, M., Huppi, K., Usuda, S., Okazaki, K., Yoshida, K. & Sakano, H.
      (1991) Mol. Cell. Biol. 11, 4528-4536]. These sequences have been postulated to
      form stem-loop structures, further implicating local bends and unwinding in DNA
      as a recognition target for HMG-box proteins. Expression analysis in a variety of
      tissues and cisplatin-resistant cell lines and the inability of cisplatin to
      induce the message in HeLa cells argue against a direct link between SSRP1 mRNA
      levels and the response of cells to the drug.

PMID- 1372441
TI  - A conditional yeast mutant deficient in mRNA transport from nucleus to cytoplasm.
AB  - Transport of mRNA from nucleus to cytoplasm is critical for eukaryotic gene
      expression; however, the mechanism of export is unknown. Selection and screening
      procedures have therefore been used to obtain a family of temperature-sensitive
      conditional mutants of Saccharomyces cerevisiae that accumulate poly(A)+ RNA in
      the nucleus when incubated at 37 degrees C, as judged by in situ hybridization.
      In one such mRNA transport mutant, mtr1-1, RNA synthesis continues, the export of
      poly(A)+ RNA is inhibited, intranuclear poly(A)+ is remarkably stable, and
      protein synthesis gradually stops. Thus, there is no tight coupling between RNA
      synthesis and export. The export lesion is reversible. Although mRNA export is
      clearly not a default option, neither inhibition of protein synthesis, inhibition
      of mRNA splicing, nor inhibition of poly(A)-binding protein function blocks
      export of the average poly(A)+, as judged by in situ hybridization. Further
      analysis of the family of mtr mutants should help map the path of RNA transport.

PMID- 1372442
TI  - Characterization of the cystic fibrosis transmembrane conductance regulator in a
      colonocyte cell line.
AB  - An anti-peptide antibody raised to the C-terminal sequence of the cystic fibrosis
      transmembrane conductance regulator (CFTR) was used to examine CFTR
      immunoreactivity in the T84 colonocyte cell line. Immunoblots of T84 cell lysates
      detected CFTR as a 170-kDa protein that appeared as a broad band or doublet in
      SDS/PAGE. This protein comigrated with the predominant immunoblot signal detected
      in human pancreas and colon. An equivalent protein was detected as a prominent
      substrate for protein kinase A and for protein kinase C in T84 cell
      immunoprecipitates with this antibody. The immunoprecipitated protein resembled
      the protein detected by immunoblot in that both proteins showed the same change
      in electrophoretic mobility after digestion by N-Glycanase. The precipitated
      protein was indentified as CFTR by two criteria. First, the same protein was
      immunoprecipitated with an antibody to a different CFTR peptide, [Lys102]CFTR
      (102-116). Second, two-dimensional phosphopeptide mapping was used to compare the
      immunoprecipitated protein with a bacterially expressed protein known to contain
      most of the predicted protein kinase A phosphorylation sites in CFTR. Because the
      six most prominent peptides in each map were equivalent, these maps confirm that
      the precipitated protein is CFTR. By using these antibodies for
      immunofluorescence and immunoperoxidase staining, CFTR was localized to the
      apical region of T84 cells grown in tumors and in monolayers. Thus, T84 cells
      express CFTR at sufficient levels to permit identification and immunochemical
      studies of this protein in its endogenously occurring form.

PMID- 1372444
TI  - The Na+/H+ antiporter cytoplasmic domain mediates growth factor signals and
      controls "H(+)-sensing".
AB  - The amiloride-sensitive Na+/H+ exchanger (NHE1 human isoform) is activated in
      response to diverse mitogenic and oncogenic signals presumably through
      phosphorylation. To get insight into the activating mechanism, a set of deletion
      mutants within the C-terminal cytoplasmic domain of NHE1 has been generated.
      These mutant forms expressed in antiporter-deficient fibroblasts revealed that
      deletion of the complete cytoplasmic domain (i) preserves amiloride-sensitive
      Na+/H+ exchange and activation by intracellular H+, (ii) reduces the affinity of
      the internal "H(+)-modifier site" in a manner mimicked by cellular ATP depletion,
      and (iii) abolishes growth factor-induced cytoplasmic alkalinization. We conclude
      that NHE1 can be separated into two distinct functional domains. One is an N
      terminal transporter domain (T) that has all the features required to catalyze
      amiloride-sensitive Na+/H+ exchange with a built-in H(+)-modifier site. The other
      is a C-terminal cytoplasmic regulatory domain (R) that (i) determines the set
      point value of the exchanger and (ii) mediates growth factor signals by
      interacting with the "H(+)-sensor" in a phosphorylation-dependent manner.

PMID- 1372443
TI  - Preproenkephalin promoter "cassette" confers brain expression and synaptic
      regulation in transgenic mice.
AB  - The preproenkephalin A gene is a neurotransmitter gene whose expression can be
      modulated "trans-synaptically" by changes in neuronal activity. DNA sequences
      lying within 200 base pairs of this gene's transcription start site resemble
      consensus binding sites for several transcription factor families. In nonneuronal
      cell cultures, this promoter region is sufficient to mediate gene responses to
      depolarization, phorbol esters, adenylate cyclase, and calcium fluxes. To assess
      the role that these cis-acting elements could play in preproenkephalin expression
      and regulation in vivo, the expression of a construct containing this 200-base
      pair region fused to the chloramphenicol acetyltransferase gene was examined in
      transgenic mice. This promoter confers modest expression in brain, adrenal, and
      small intestine, with substantially higher levels in testis. These elements
      confer trans-synaptic regulation in two well-studied models of trans-synaptic
      preproenkephalin upregulation but not in a third system, underscoring the
      specificity of the regulatory sequence elements implicated in the synaptic
      regulation of neuronal genes.

PMID- 1372445
TI  - Cloning of a D-type cyclin from murine erythroleukemia cells.
AB  - We report the complete coding sequence of a cDNA, designated CYL2, derived from a
      murine erythroleukemia cell library. CYL2 is considered to encode a D-type cyclin
      because (i) there is cross hybridization with CYL1 (a murine homolog of human
      cyclin D1) and the encoded protein has 64% amino acid sequence identity with CYL1
      and (ii) murine erythroleukemia cell-derived CYL2 contains an amino acid sequence
      identical to that previously reported for the C-terminal portion of a partially
      sequenced CYL2. Transcripts of murine erythroleukemia cell CYL2 undergo
      alternative polyadenylylation like that of human cyclin D1. A major 6.5-kilobase
      CYL2 transcript changes its expression during the cell cycle with a broad peak
      through G1 and S phases and a decrease in G2/M phases. The present findings
      suggest that CYL2 plays a role in the G1 to S phase progression.

PMID- 1372447
TI  - [Protein engineering of amylases and proteases].

PMID- 1372449
TI  - Surgical treatment of gastric cancer. Proximal, mid, and distal stomach.
AB  - At present, only radical surgical resection of gastric cancer offers a chance for
      cure. The objective of an operation for patients with disease that is confined
      locally is to maximize the potential for cure. The objective for patients with
      advanced incurable disease, obstruction, hemorrhage, and intractable pain is to
      provide the best palliation. The evaluation, staging, and surgical management of
      gastric cancer are described.

PMID- 1372446
TI  - Down-regulation of a member of the S100 gene family in mammary carcinoma cells
      and reexpression by azadeoxycytidine treatment.
AB  - A cDNA clone, designated CaN19 (originally called clone 19), isolated by
      subtractive hybridization, contains sequences that are preferentially expressed
      in normal mammary epithelial cells but not in breast tumor cells. Comparison of
      its deduced amino acid sequence with sequences in the GenBank data base revealed
      similarity with the S100 protein family, a group of small Ca(2+)-binding
      modulator proteins involved in cell cycle progression and cell differentiation.
      CaN19 expression is down-regulated in normal cells by A23187, a calcium
      ionophore, suggesting that its regulation is calcium-dependent. We have assigned
      CaN19 to human chromosome 1q21-q24, a region containing four other S100-related
      genes. In contrast to CaN19 mRNA expression, most members of the S100 protein
      family are activated or overexpressed in tumor cells. Synchronization experiments
      by growth-factor deprivation demonstrated a biphasic induction of CaN19
      expression in normal cells, approximately 2-fold in early G1 phase and another 2-
      to 3-fold at the G1/S boundary. Exposure of mammary tumor cells to 5-aza-2'
      deoxycytidine, an inhibitor of DNA methylation, reactivated the expression of
      CaN19 mRNA.

PMID- 1372448
TI  - Induction of broadly cross-reactive cytotoxic T cells recognizing an HIV-1
      envelope determinant.
AB  - An immunodominant determinant for cytotoxic T lymphocytes (CTLs) exists in the
      hypervariable portion of human immunodeficiency virus-1 (HIV-1) gp160. Three
      mouse CTL lines (specific for isolates MN, RF, and IIIB) were examined for
      recognition of homologous determinants from distinct isolates. Only MN-elicited
      CTLs showed extensive interisolate cross-reactivity. Residue 325 played a
      critical role in specificity, with MN-elicited CTLs responding to peptides with
      an aromatic or cyclic residue and IIIB-induced cells recognizing peptides with an
      aliphatic residue at this position. CTL populations with broad specificities were
      generated by restimulation of IIIB-gp160 primed cells with MN-type peptides that
      have an aliphatic substitution at 325. This represents an approach to synthetic
      vaccines that can generate broadly cross-reactive CTLs capable of effector
      function against a wide range of HIV isolates.

PMID- 1372450
TI  - New perspectives in lung cancer. 4. Haematopoietic growth factors and lung cancer
      treatment.

PMID- 1372451
TI  - Sputum sol phase proteins and elastase activity in patients with clinically
      stable bronchiectasis.
AB  - BACKGROUND: Inflammatory and proteolytic activity occurs in sputum from patients
      with stable purulent bronchiectasis and has been proposed as the main
      pathogenetic mechanism of the disease. This study was designed to define further
      the role of inflammation and proteolysis in bronchiectasis. METHODS: Neutrophil
      elastase activity, sputum concentrations of the serum derived inhibitors alpha 1
      antiproteinase and alpha 2 macroglobulin, and the sputum to serum ratios of
      albumin and C reactive protein concentration were measured in 26 patients with
      bronchiectasis. RESULTS: Free elastase activity was found in 15 sputum samples. A
      trend to higher proteolytic and inflammatory activity was found between mucoid
      and purulent sputum samples, suggesting that inflammatory and proteolytic
      activities are related to the macroscopic degree of purulence. Purulent sputum
      had a high sputum to serum ratio of C reactive protein, suggesting local
      production or active transport of this protein into bronchial secretions. C
      reactive protein was more sensitive than albumin in detecting a higher degree of
      inflammation in elastase positive samples. CONCLUSION: The finding of greater
      concentrations of alpha 2 macroglobulin in purulent and elastase positive samples
      than in mucopurulent, mucoid and elastase negative sputum samples suggests that
      this inhibitor may have a role in the proteolysis-antiproteolysis balance in
      bronchial secretions.

PMID- 1372452
TI  - A comparison of endocrine and exocrine function after pancreatic fragment
      autotransplantation into splenic pulp, portal vein, and hepatic parenchyma.
AB  - Three sites were evaluated for potential pancreatic fragment autotransplantation.
      Both endocrine and exocrine functions were evaluated following
      autotransplantation into splenic pulp, portal vein, or hepatic parenchyma in 44
      pancreatectomized dogs. Cholecystic bile amylase concentrations in the hepatic
      parenchyma group surviving more than 2 months were elevated significantly, and
      choledochal bile amylase concentrations increased markedly following pancreozymin
      secretin injection. In contrast, bile amylase concentrations in dogs with
      intrasplenic or intraportal implants were low and did not respond to PS
      injection. Histologically pancreatic autografts in hepatic parenchyma revealed
      marked proliferation of exocrine tissue with abundant zymogen granules and
      reconstruction of the acinar lobules with a few islets. These acinar cells in the
      hepatic parenchyma were ultrastructurally normal. Transplant endocrine function,
      estimated by K values, was significantly better after splenic pulp and portal
      vein than after a hepatic parenchyma implantation, but no group improved during 1
      year follow-up. Glucose-stimulated initial insulin responses were abnormally low
      in all recipients. Islet B cells lacked mature insulin granules, such as seen in
      normal resting B cells. This ultrastructural finding implies a persistent demand
      on the B cells and may explain the spontaneous recurrence of hyperglycemia and
      the diminished initial insulin response to a glucose load. This study indicates
      that euglycemic recipients of pancreatic fragment autotransplantation remain
      unstable and prediabetic.

PMID- 1372453
TI  - Evidence that nitric oxide production by in vivo allosensitized cells inhibits
      the development of allospecific CTL.
AB  - The oxidative metabolism of L-arginine to its bioactive product, nitric oxide (.N
      = O) has been shown to inhibit rat splenocyte mixed lymphocyte reactions. To
      determine if alloantigen-induced .N = O production might be operative in vivo,
      cells that had infiltrated a rat sponge matrix allograft were tested for de novo
      .N = O production as well as .N = O production upon restimulation with the
      sensitizing alloantigen. When graft-infiltrating cells were placed in culture, a
      peak in de novo .N = O production was observed by day 6 graft-infiltrating cells,
      the time when donor-specific CTL activity by the graft-infiltrating cells was
      first observed. Upon restimulation with alloantigen, allograft-infiltrating cells
      produced greatly increased levels of .N = O, and this production was associated
      with inhibition of lymphocyte cytolytic function. The addition of NG-monomethyl-L
      arginine (NMA), the competitive inhibitor of oxidative L-arginine metabolism,
      inhibited .N = O production and promoted allospecific CTL development. Both
      observed effects of NMA were reversed by addition of excess L-arginine.
      Cytokine(s) able to induce proliferation of the IL-2-dependent T cell line CTLL-2
      could be detected in alloantigen-stimulated cultures in both the presence and
      absence of NMA. However, proliferation of the graft-infiltrating cells in
      response to these cytokines was observed only in the presence of NMA. The
      immunosuppressive macrolide FK506 was a potent inhibitor of .N = O production in
      these cultures, presumably acting by inhibiting the production of those cytokines
      that induce the oxidative L-arginine pathway.

PMID- 1372454
TI  - Sequential analysis of IL-2 gene transcription in renal transplants.

PMID- 1372455
TI  - Hyperamylasemia associated with pancreatic graft arterial stenosis in combined
      kidney-pancreas transplantation.

PMID- 1372456
TI  - Acute experimental pancreatitis in rat induced by sodium taurocholic acid:
      objective quantification of pancreatic necrosis.
AB  - Retrograde injection of 5% sodium taurocholic acid (TA) in Wistar rat pancreatic
      duct is followed by acute pancreatitis, resulting in 100% mortality within 36 h.
      Biochemical determinations show raised levels of amylase in ascites and blood.
      Necrosis has been measured using seven morphometric characteristics of
      pathological changes that add precise information on the type and extension of
      the pancreatic lesion. The percentage of necrotic tissue (by area) seems to be
      the most objective parameter. Necrosis appears 6 h after TA infusion, being 5.77%
      in extent after 12 h, 14.9% after 24 h and animals die with an area of 29.5%
      necrosis. This experimental model seems to one in which physiopathological and
      therapeutic trials on acute pancreatitis may be tried out.

PMID- 1372457
TI  - Microcytic variant of thymoma: histological and immunohistochemical findings in
      two cases.
AB  - Two cases of microcytic variant of thymoma are presented. Both tumours were well
      encapsulated with a yellow-whitish colour and soft consistency. Microscopically,
      they consisted of round cells, having ample vacuolated cytoplasm. Fat droplets
      were not detected in one case where fat staining was performed.
      Immunohistochemically, the tumour cells were strongly positive for AE1/AE3, MB1,
      MB2, and LN1 and faintly positive for epithelial membrane antigen. They lacked
      any other leucocyte antigens. Leu 7 showed a positive immunoreaction in a ring
      like or homogeneous pattern, compatible with the cytoplasmic vacuoles or
      cytoplasm. Ultrastructurally, the vacuoles resembled cystically dilated rough
      surfaced endoplasmic reticulum. Desmosome-like structures (case 1) and
      intermediate junctions (case 2) were identified between adjacent cells. These
      findings indicate that the present tumours belong to a category of microcystic
      thymoma. The vacuoles were attributed to excess accumulation of Leu-7-positive
      material, probably in the cystically dilated endoplasmic reticulum.

PMID- 1372459
TI  - [Significance of pathological alpha-1-fetoprotein levels in the framework of
      prenatal diagnosis].
AB  - Merkatz (1984) showed that in 68% of live birth with Down Syndrome maternal age
      was 34 years or less. It would be desirable to define a high risk collective of
      women younger then 35 years with the help of a screening test, which could
      further on lead to a prenatal diagnostics. Several studies showed that low
      maternal serum alpha-fetoprotein levels (SAFP) in pregnancy is associated with
      fetal chromosomal abnormalities. The results of a retrospective study at the
      Department of Obstetrics and Gynecology at University of Mainz showed that
      maternal SAFP-level does not accomplish the demand of a prenatal screening test,
      because only 17% of the Down Syndrome could be diagnosed by this parameter. In
      case of trisomy 13 and 18 SAFP-concentrations were normal or even increased,
      maybe on account of the combination with other malformations like neural-tube or
      abdominal-wall defects.

PMID- 1372458
TI  - Primary thymic carcinoid with Cushing's syndrome.
AB  - In a 52-year-old Caucasian man osteopoikilosis had been misdiagnosed
      roentgenologically 2 years before his death. Gradually he developed Cushing's
      syndrome and ultimately superior vena caval obstruction. At autopsy a primary
      thymic carcinoid with extensive osteoblastic bone metastasis was found.
      Immunohistochemically the tumor was shown to be positive for adrenocorticotropic
      hormone (ACTH), cytokeratin (KL1), neuron-specific enolase, synaptophysin,
      chromogranin and glucagon. Remarkably the tumour was negative for serotonin
      despite high urinary hydroxyindolacetic acid levels. Bilateral hyperplasia of the
      adrenal cortex was found. The adenohypophysis showed a considerable reduction of
      ACTH-producing cells and numerous Crooke's cells with a characteristic
      immunohistochemical pattern.

PMID- 1372460
TI  - [Distal post-traumatic edema--symptom of a sympathetic reflex dystrophy (Sudeck's
      disease)?].
AB  - The present paper describes various mechanisms, possibly being involved in the
      development of the posttraumatic, distally generalized edema. New ideas point to
      a special importance of the sympathetic vasoconstrictor system for this clinical
      phenomenon, since this system could induce an enhanced venoconstriction at the
      exit of the capillary bed, which would result in an edema producing diminished
      venous return. Since the distally generalized edema is an initially and very
      commonly occurring symptom of reflex sympathetic dystrophy (M. Sudeck), the
      observation of such an edema should lead one to look for further symptoms of this
      disorder, especially for the typical triad of autonomic (sympathetic), motor, and
      sensory disturbances.

PMID- 1372461
TI  - Synergistic action of postextrasystolic potentiation and diperdipine on left
      ventricular wall motion abnormalities in coronary heart disease.
AB  - The effects on left ventricular function of postextrasystolic potentiation and
      the dihydropyridinic calcium antagonist diperdipine, alone or in combination,
      were studied in 14 patients with coronary heart disease by means of two
      consecutive left ventricular angiographies. To ensure the reproducibility of
      coupling intervals of the extrasystolic and postextrasystolic beats, the heart
      was paced during both angiographies. Results showed that postextrasystolic
      potentiation and diperdipine improved left ventricular ejection fraction to the
      same degree, but the mechanisms of such an improvement were different and
      consisted, respectively, of a positive inotropic effect associated with an
      increase in preload and a slight increase in preload coupled with a marked
      decrease in afterload. Diperdipine did not abolish the inotropic component of
      postextrasystolic potentiation, and a combination of the two interventions had
      additive effects on the improvements in left ventricular ejection fraction and
      regional wall motion analyzed by the centerline method. Ventricular segments that
      were normokinetic or hypokinetic during the control basal cycle responded equally
      to postextrasystolic potentiation and to diperdipine, whereas the former
      intervention alone had no significant effect on akinetic segments. Diperdipine
      restored the responsiveness of akinetic segments to postextrasystolic
      potentiation, a finding that, although it remains to be confirmed by independent
      techniques, may be interpreted as a possible consequence of improved calcium
      metabolism or coronary flow in ischemic but still viable myocardium. However, it
      is concluded that the calcium antagonist revealed a contractile reserve in most
      of the severely asynergic areas, which would have otherwise been judged to be
      irreversibly damaged on the basis of the unresponsiveness to postextrasystolic
      potentiation alone.

PMID- 1372462
TI  - Mechanism of concealed bigeminy.

PMID- 1372463
TI  - Weekly dose-intensive chemotherapy in patients with small-cell lung cancer: a
      pilot study.
AB  - The study was aimed to evaluate the feasibility of dose-intensive chemotherapy
      given on a weekly basis for 12 weeks. Seventeen [7 with limited disease (LD) and
      10 with extensive disease (ED)] previously untreated patients with small-cell
      lung cancer (SCLC) were treated with the cisplatin, vincristine, doxorubicin, and
      etoposide (CODE) regimen. Recombinant human granulocyte colony-stimulating factor
      (rhG-CSF) was given to eight patients for the purpose of increasing the dose
      intensity. Overall response rate was 88%, with a 29% complete response. The
      median survival times were greater than 20.5 months for LD patients and 8.1
      months for ED patients. Overall actual dose intensity was 88% of planned
      protocol. The major toxicity was myelosuppression. Fifteen patients (88%) had
      grade 3 or 4 leukopenia. Other problems were weight loss and worsening of
      performance status during the treatment. RhG-CSF significantly reduced leukopenic
      nadirs and shortened the neutropenic period. Our preliminary results indicate
      that 12 cycles of the CODE regimen on a weekly schedule is effective for SCLC,
      but is also associated with significant toxicity.

PMID- 1372465
TI  - Erythropoietin affects the maturation pattern of fetal G-CSF-responsive
      progenitors.
AB  - A transient hyporegenerative neutropenia has been reported in neonates, but not
      in older children or adults, undergoing treatment with recombinant erythropoietin
      (epo). Monocytopenia has not been reported. We postulated that epo might
      selectively reduce the responsiveness of neonatal progenitors to Granulocyte
      Colony-Stimulating Factor (G-CSF), while not similarly affecting their
      responsiveness to Macrophage Colony-Stimulating Factor (M-CSF). To test this
      hypothesis two types of experiments were performed. First, progenitors of adult
      or fetal origin were pre-incubated with epo (or control), then washed, and their
      responsiveness to G-CSF and M-CSF evaluated in clonogenic culture assays. Second,
      clonogenic maturation was initiated using either G-CSF or M-CSF, after which the
      effect of a late addition of epo to the developing clones was evaluated. Indeed,
      pre-incubation with epo resulted in production of fewer neutrophils from fetal
      progenitors grown in G-CSF (P less than 0.001), but it did not reduce the number
      of macrophages generated from progenitors grown in M-CSF. Adding epo to the
      already-developing G-CSF-responsive and M-CSF-responsive adult and fetal clones
      did not alter colony development. Thus, epo appears to have an action on G-CSF
      responsive, but not-M-CSF-responsive fetal progenitors, resulting in reduced
      production of neutrophils. This effect is no longer apparent, however, when
      progenitors have matured to the 8-cell clone stage.

PMID- 1372464
TI  - Treatment and prognosis of orbital non-Hodgkin's lymphomas.
AB  - Twenty patients with orbital lymphomas were treated and followed over a 14-year
      period. Ten of these patients had well-differentiated lymphocytic lymphoma (WDL),
      and all of them were clinical stage IE. Five patients had nodular poorly
      differentiated lymphocytic lymphomas (NPDL), three patients had diffuse
      histiocytic lymphomas (DHL), one had nodular mixed-cell lymphoma, and one had
      diffused mixed-cell lymphoma. The patients with WDL received local radiation
      therapy, and all of them entered completed remissions. The projected survival at
      10 years was 100% for these patients. The patients with low-grade lymphomas with
      advanced disease were treated with chlorambucil and prednisone or cytoxan and
      vincristine. The patients with high-grade lymphomas received treatment with
      methotrexate, cyclophosphamide, doxorubicin, vincristine, bleomycin,
      dexamethasone (mBACOD) or cyclophosphamide, vincristine, methotrexate, cytosine
      arabinoside, leucovorin (COMLA). The overall survival estimate for all patients
      was 63% at 10 years. The disease-free survival was 49% at 10 years. The patients
      with high-grade lymphomas had a poor prognosis, with no survivors after 4 years.
      This study suggests that patients with WDL usually present with localized disease
      to the involved orbit, and have an excellent prognosis with radiation therapy
      alone. Patients with high-grade orbital non-Hodgkin's lymphomas have a poor
      outcome despite use of aggressive combination chemotherapy regimens.

PMID- 1372466
TI  - Fluctuations in serum cytokine levels in the patient with cyclic neutropenia.
AB  - The fluctuations of the levels of serum cytokines in a patient with cyclic
      neutropenia were studied. The greatest fluctuation was found in granulocyte
      colony-stimulating factor (G-CSF). Tumor necrosis factor-alpha level fluctuated
      inversely with fluctuation of G-CSF, and oscillation of interleukin (IL)-6 level
      preceded that in G-CSF level. It is likely that the variations of the levels of
      cytokines play a significant role in regulating hematopoiesis in cyclic
      neutropenia. Our results suggested that the stage of the granulocyte-committed
      stem cell is the major step of the defect, and the defect at the stage of the
      multipotent stem cell or bone marrow microenvironment was also suggested.

PMID- 1372467
TI  - A rise of erythrocytes and platelets in a patient with myelodysplastic syndrome
      during the administration of G-CSF.

PMID- 1372468
TI  - Circulating CD34+ cells: an adverse prognostic factor in the myelodysplastic
      syndromes.
AB  - As part of an epidemiological survey of myelodysplastic syndromes (MDS) in
      southern Tasmania, 62 MDS patients identified over a 2 year period were tested
      for the presence of CD34, the human progenitor cell antigen (HPCA), in their
      peripheral blood. The results were correlated with transformation to acute
      myeloid leukemia (AML) and patient survival, and CD34+ status was compared as a
      prognostic indicator with Bournemouth score, cytogenetics, and CFU-GM colony
      growth which were also assessed. Circulating CD34+ cells were found in 23 of the
      62 MDS patients; 9 of the 23 patients with circulating CD34+ cells transformed to
      AML, as compared with none of the 39 CD34 negative patients (P less than 0.0001);
      and 11 of the 23 patients with circulating CD34+ cells were dead at the end of
      the 2 year period, as opposed to 6 of the 39 with no CD34+ cells (P less than
      0.03). The Bournemouth score was also significantly associated with
      transformation to AML (P less than 0.0001) and poor survival (P less than 0.04).
      These were the only significant associations of the possible prognostic factors
      studied with either transformation or survival. In summary, the presence of
      circulating CD34+ cells was significantly associated with both progression to AML
      and poor survival and was found to be a better prognostic indicator than
      cytogenetics or CFU-GM colony growth.

PMID- 1372469
TI  - Xeroderma pigmentosum and Cockayne syndrome: overlapping clinical and biochemical
      phenotypes.
AB  - Two siblings are described whose clinical presentation of cutaneous
      photosensitivity and central nervous system dysfunction is strongly reminiscent
      of the DeSanctis-Cacchione syndrome (DCS) variant of xeroderma pigmentosum. An
      extensive clinical evaluation supported a diagnosis of DCS and documented
      previously unreported findings. In vitro fibroblast studies showed UV sensitivity
      that was two to three times that of normal controls. However, neither a post-UV
      irradiation DNA excision-repair defect indicative of XP nor a semiconservative
      DNA replication defect indicative of XP variant was found. Rather, a failure of
      RNA synthesis to recover to normal levels after UV exposure was observed, a
      biochemical abnormality seen in Cockayne syndrome (CS), one of the premature
      aging syndromes with clinical UV sensitivity. These patients, therefore,
      clinically have XP, but their biochemical characteristics suggest CS. The
      reason(s) for the severe neurologic disease, in light of the relatively mild
      cutaneous abnormalities, is unclear. Other cases with unusual fibroblast
      responses to irradiation have been noted in the literature and, along with the
      data from our patients, reinforce the notion of the complexity of DNA maintenance
      and repair.

PMID- 1372470
TI  - Superficial laser vulvectomy. V. Surgical debulking is enhanced by adjuvant
      systemic interferon.
AB  - Skillful laser ablation can remove any volume of human papillomavirus-associated
      vulvar disease but cannot prevent reactivation of the surrounding latent viral
      reservoir during postoperative healing. Conversely, interferon and 5-fluorouracil
      are relatively ineffective as primary therapies in clearing bulky lesions. In
      this study of 71 assessable patients, topical 5-fluorouracil and systemic
      interferon injections were used postoperatively. Success rates within the
      adjuvant 5-fluorouracil and laser alone arms were essentially the same (9 of 18
      vs 8 of 20). In contrast, outcome in the interferon group was significantly
      better than that for the other two arms combined (27 of 33 [82%] vs 17 of 38
      [45%]; chi 2 10.31; p less than 0.002). Moreover, 18 of 21 failures (86%) in the
      first two arms and 3 of 6 failures (50%) in the interferon arm were "rescued"
      from the need for a second laser surgical procedure by crossover to either the 1
      or 3 MIU interferon regimen. Results from this open-label, randomized clinical
      trial suggest that even a relatively low dose of recombinant interferon, used in
      combination with effective surgical debulking, can markedly reduce the risk of
      postoperative recurrence.

PMID- 1372471
TI  - Immunohistochemical detection of the multi-drug-resistance marker P-glycoprotein
      in uterine cervical carcinomas and normal cervical tissue.
AB  - Uterine cervical carcinomas and normal cervical tissue (controls) were
      investigated for the presence of the multi-drug-resistance gene product P
      glycoprotein by means of immunohistochemistry, with the C219 monoclonal antibody
      and the streptavidin-biotin-peroxidase technique. Ten of 11 cervical carcinomas,
      2 of which were previously treated with chemotherapeutic agents of the multi-drug
      resistance group, showed a positive reaction of tumor cells. All normal controls
      showed a positive reaction of the ectocervical and endocervical epithelial cells.
      P-glycoprotein seems to be implicated at least in part in resistance to
      chemotherapy of cervical carcinoma.

PMID- 1372472
TI  - Is trichomoniasis often associated with bacterial vaginosis in pregnant
      adolescents?
AB  - The same criteria for identifying bacterial vaginosis are often present in women
      with trichomoniasis. These criteria include elevated vaginal pH, vaginal odor,
      homogeneous discharge, increased anaerobic bacteriologic vaginal flora, and
      elevated levels of bacterial enzymes. Clinically mixed vaginal infections occur,
      and because the treatment for these two conditions can be different, it is
      important to distinguish between them. Trichomoniasis can interfere with a Gram
      stain diagnosis or the proline aminopeptidase test for bacterial vaginosis. Clue
      cells are not generally found in women with Trichomonas vaginalis, but when
      present, they strongly indicate the concomitant presence of bacterial vaginosis.

PMID- 1372473
TI  - Ultrasonographic dating of pregnancy causes significant errors in Down syndrome
      risk assessment that may be minimized by use of biparietal diameter-based means.
AB  - OBJECTIVES: Gestational dates assessed by ultrasonographic measurement of fetal
      dimensions are usually quoted in terms of complete weeks because the uncertainty
      of ultrasonographic measurement is approximately +/- 7 days. This study examines
      the effect of ultrasonographic dating on Down syndrome risk assessment. STUDY
      DESIGN: The effect of small changes in measured biparietal diameter resulting in
      a change in estimated gestational week and the benefits of a more precise measure
      of fetal gestational age (raw biparietal diameter) are examined mathematically.
      RESULTS: If maternal serum alpha-fetoprotein and human chorionic gonadotropin are
      used to assess Down syndrome risk, risks assessed with ultrasonographically
      determined dates may be less than or equal to 45% too high for fetuses with
      biparietal diameter at the lowest end of the size band and less than or equal to
      22% too low with biparietal diameter at the top of the size band. If the results
      for maternal serum alpha-fetoprotein, human chorionic gonadotropin, and
      unconjugated estriol are used, these figures become less than or equal to 150%
      and less than or equal to 60%, respectively. CONCLUSION: If ultrasonography is
      used to assess gestational age, the raw biparietal diameter and not the estimated
      week of gestation must be used to derive means for calculation of multiples of
      the mean.

PMID- 1372474
TI  - Characteristics of three vaginal flora patterns assessed by gram stain among
      pregnant women. Vaginal Infections and Prematurity Study Group.
AB  - This study was undertaken to define the characteristics and persistence of
      vaginal flora in 7918 pregnant women at 23 to 26 weeks' gestation. Vaginal smears
      were categorized as normal (predominant lactobacilli), intermediate (reduced
      lactobacilli), or positive for bacterial vaginosis. The women with normal flora
      were least likely to have elevated vaginal pH, amine odor, milky discharge, or
      colonization by Gardnerella, Bacteroides, or genital mycoplasmas. Women with
      intermediate vaginal flora had intermediate frequencies of these clinical signs
      and microorganisms. Group B streptococci and yeast were associated with normal or
      intermediate flora, whereas Neisseria gonorrhoeae and Chlamydia trachomatis were
      recovered more frequently from women with intermediate flora or bacterial
      vaginosis. Trichomonas vaginalis was most associated with intermediate flora. At
      follow-up, 81% of the women with normal flora had remained normal. Of the women
      with intermediate flora, 32% acquired bacterial vaginosis and 30% shifted to
      normal flora. Only 12% of the women with bacterial vaginosis had shifted to
      normal flora. We conclude that there are two primary stable vaginal flora
      patterns (normal flora or bacterial vaginosis) and a third less distinct
      transitional flora pattern between these two.

PMID- 1372475
TI  - Unexplained elevated maternal serum alpha-fetoprotein is not predictive of
      adverse perinatal outcome in an indigent urban population.
AB  - OBJECTIVE: The null hypothesis of this study is that in an urban, indigent
      obstetric population at high risk for adverse perinatal outcome, unexplained
      elevations of maternal serum alpha-fetoprotein are not an additional predictor of
      adverse perinatal outcome. STUDY DESIGN: Perinatal outcomes of 72 patients from a
      clinic for indigent patients with unexplained elevated maternal serum alpha
      fetoprotein levels were compared with those of matched controls from the same
      population with normal maternal serum alpha-fetoprotein levels. Subjects and
      controls were matched for age, race, parity, and presence or absence of Hollister
      risk factors. The frequency of adverse perinatal outcome in the two groups was
      subjected to matched-pair chi 2 analysis. RESULTS: Adverse perinatal outcome
      occurred in 38.9% (28 of 72) of subjects with unexplained elevated maternal serum
      alpha-fetoprotein levels greater than or equal to 2.5 multiples of the median,
      compared with 31.9% (23 of 72) of controls with normal maternal serum alpha
      fetoprotein levels (p = 0.5). No statistically significant difference in adverse
      perinatal outcomes was found. CONCLUSIONS: Elevated maternal serum alpha
      fetoprotein levels offer little if any additional predictive value for adverse
      perinatal outcome in populations already at high risk for such outcomes on the
      basis of obstetric or socioeconomic criteria.

PMID- 1372476
TI  - Substance P: a late-acting B lymphocyte differentiation cofactor.
AB  - The peptide substance P has been recognized for years as having dramatic effects
      on such diverse physiological responses as blood pressure regulation, peristalsis
      of the gut, and salivation. More recently, demonstration of substance P receptors
      on leukocytes and modulation of leukocyte functions by this peptide suggested
      that it might also have a role in immune regulation. This review focuses on the
      growing body of evidence that demonstrates substance P-induced effects on one
      population of leukocytes, namely B lymphocytes. Despite the diversity of
      experimental techniques used, there is surprisingly good agreement as to the role
      substance P has in modulating B lymphocyte responses. In vivo treatments of
      rodents, which increase substance P concentrations in the periphery, increase the
      number of immunoglobulin-secreting cells in these animals. Conversely, infusion
      of substance P antagonists or depletion of substance P-containing neurons in
      rodents substantially reduces the animals' ability to synthesize immunoglobulins.
      With the use of cultures of B lymphocytes it was possible to demonstrate similar
      results. In the presence of polyclonal B cell activators, substance P augmented
      immunoglobulin secretion in cultures of purified B lymphocytes or B cell clones.
      The absence of accessory cells in these cultures suggested that substance P could
      act directly on activated B lymphocytes, and in fact these B cells were shown to
      express specific receptors for this peptide. It appears that the substance P
      receptors expressed by leukocytes are similar or identical to those expressed by
      neurons as evidenced by radioreceptor binding assays and detection of the gene
      encoding the substance P receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372477
TI  - T84 cells: anion selectivity demonstrates expression of Cl- conductance affected
      in cystic fibrosis.
AB  - The T84 cell line possesses an adenosine 3',5'-cyclic monophosphate (cAMP)
      activated Cl- conductance and expresses high levels of the cystic fibrosis (CF)
      gene product, implicating it as a good model for CF research. To evaluate whether
      T84 Cl- conductance properties are consistent with those described in CF target
      epithelial, we used transepithelial measurements (verified by selective
      permeabilization of the basal membrane) to determine the apparent anion
      selectivity properties of the apical and basolateral membranes of stimulated and
      unstimulated T84 cells. Unstimulated epithelial cells were almost electrically
      inert, having a low transepithelial voltage (Vt; -6 mV, apical surface negative),
      a small equivalent short-circuit current (Isc,(eq.) 2.2 microA/cm2), a very high
      transepithelial resistance (Rt; 2,500 omega.cm2), and poor anion permselectivity
      properties at both membrane surfaces (0.8 less than PX/PCl- less than 1.1), where
      X is NO3-, Br-, I-, or gluconate. When stimulated with forskolin (10(-6) M), Vt
      increased 8-fold, Isc(eq) increased 30-fold, Rt fell to one-third of unstimulated
      values, and the apical surface became highly anion selective, i.e., NO3- (1.4)
      greater than Br- (1.2) greater than Cl- (1.0) greater than I- (0.7) greater than
      gluconate (0.0), where numbers in parentheses are PX/PCl-. I- was less permeable
      than Cl- and probably directly inhibits the anion conductance, since Rt was
      substantially greater after I- substitution than after substitution with the
      impermeable anion gluconate. Bumetanide (10(-4) M) significantly attenuated the
      response of Vt to anion substitutions at the basal membrane surface, indicating
      that the effects of substitution were predominantly on the Na(+)-K(+)-2Cl-
      cotransporter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372478
TI  - Regulation of sarcoplasmic reticulum gene expression during cardiac and skeletal
      muscle development.
AB  - The expression of major sarcoplasmic reticulum proteins during cardiac and fast
      twitch skeletal muscle development was examined using gene-specific probes.
      Through the use of S1 nuclease mapping, Northern blot, and RNA slot-blot
      analysis, sarcoplasmic reticulum proteins were shown to exhibit both narrow
      tissue specificity and plasticity in their expression during muscle development.
      In fast-twitch skeletal muscle, the cardiac/slow-twitch isoforms of Ca(2+)-ATPase
      and calsequestrin were detected at high levels in fetal stages but were gradually
      replaced by fast-twitch isoforms in adult muscle. In contrast, cardiac muscle
      expressed exclusively cardiac/slow-twitch isoforms of Ca(2+)-ATPase and
      calsequestrin at all stages. Both fast-twitch and slow-twitch skeletal muscle
      expressed the same skeletal muscle ryanodine receptor isoform, whereas cardiac
      muscle expressed a cardiac isoform. Phospholamban expression was restricted to
      cardiac and slow-twitch skeletal muscle and did not appear in developing fast
      twitch skeletal muscle. During in vitro myogenesis of C2C12 cells, the mRNA
      transcripts encoding sarcoplasmic reticulum proteins were found to be
      coordinately induced in synchrony with that of contractile protein mRNA. The
      myogenic factor "myogenin" induced sarcoplasmic reticulum gene transcripts along
      with contractile protein mRNAs in nonmyogenic cells. These data suggest that the
      induction of both sarcoplasmic reticulum and contractile protein gene families is
      under the control of a common myogenic differentiation program.

PMID- 1372479
TI  - L-type Ca2+ channel desensitization by F- reduces PhE-induced increase in [Ca2+]i
      but not stress.
AB  - F- (10 mM sodium fluoride plus deferoxamine to chelate contaminating aluminum)
      causes arterial contractions primarily by activating L-type Ca2+ channels.
      Results from the present study indicate that, although F(-)-induced contractions
      could be completely relaxed by washing out the F- with fresh buffer, a long
      lasting effect of F- pretreatment was to produce L-type Ca2+ channel
      desensitization. Pretreatment of arteries for 4 h with F- (followed by washout of
      F-) resulted in much reduced increases in stress and [Ca2+]i produced by the
      subsequent addition of 110 mM KCl, such that steady-state values were,
      respectively, only 9 and 15% of the control values. However, a 4-h F-
      pretreatment caused a reduction only in the rate of stress development, but not
      the steady-state level of stress, produced by maximum concentrations of receptor
      agonists. In tissues that were pretreated with F- and then stimulated with the
      alpha-adrenoceptor agonist, phenylephrine, steady-state stress was still 104% of
      the control value, while the increase in [Ca2+]i was only 10% of the control
      value. F- is known to inhibit protein phosphatases, and similar reductions in the
      ability of KCl to produce contractions and increase [Ca2+]i were seen after
      pretreatment with the protein phosphatase inhibitor, okadaic acid. These data
      suggest that L-type Ca2+ channel desensitization by F- pretreatment was caused by
      increased protein phosphorylation. In addition, they suggest that much of the
      contribution made by L-type Ca2+ channels to increase [Ca2+]i during receptor
      stimulation may not be necessary for the maintenance of maximum stress at steady
      state.

PMID- 1372480
TI  - Inhibition by sodium nitroprusside or PGE1 of tyrosine phosphorylation induced in
      platelets by thrombin or ADP.
AB  - Upon platelet activation, numerous proteins are known to be tyrosine
      phosphorylated. To investigate the mechanisms of the regulation of tyrosine
      phosphorylation and its physiological significance, the effects on tyrosine
      phosphorylation of agents that elevate the platelet level of the cyclic
      nucleotides cAMP and cGMP were examined in aspirin-treated gel-filtered platelets
      by Western blotting with a specific antiphosphotyrosine antibody. The effects of
      these agents on other aspects of platelet activation, i.e., aggregation,
      secretion, and elevation of the concentration of cytosolic ionized calcium
      ([Ca2+]i), were also examined in parallel experiments. Tyrosine phosphorylation
      in platelets activated by alpha-thrombin (1 nM) was inhibited by prostaglandin
      (PG) E1 (2 microM) or by sodium nitroprusside (100 microM). Elevation of [Ca2+]i,
      aggregation, and serotonin secretion was also strongly inhibited. On the other
      hand, a higher concentration of alpha-thrombin (10 nM) induced tyrosine
      phosphorylation of the same proteins, elevation of [Ca2+]i, platelet aggregation,
      and serotonin secretion, irrespective of pretreatment of platelets by either PGE1
      or sodium nitroprusside. Inhibition by sodium nitroprusside of tyrosine
      phosphorylation induced by alpha-thrombin (1 nM) was accompanied by an increased
      concentration of cGMP. 8-BrcGMP (2 mM) also inhibited tyrosine phosphorylation
      and aggregation, although less than sodium nitroprusside. ADP (20 microM) induced
      platelet shape change and tyrosine phosphorylation of only a few proteins; these
      effects were also inhibited by either PGE1 or sodium nitroprusside. Thus tyrosine
      phosphorylation in platelets can be inhibited by elevation of either cAMP or
      cGMP, an effect that is overcome by a high concentration of thrombin, resulting
      in granule secretion and aggregation. Some of the proteins that are tyrosine
      phosphorylated may be important in the regulation of platelet functions.

PMID- 1372481
TI  - Tetrodotoxin-insensitive sodium channels in a cardiac cell line from a transgenic
      mouse.
AB  - The electrophysiological properties of a cardiac cell line (MCM1) originating
      from a transgenic mouse were characterized. The dominant current in these cells
      is a sodium current that is insensitive to concentrations of tetrodotoxin (TTX)
      up to 100 microM. It activates and inactivates rapidly with half-maximal
      activation at -40 mV and half-maximal inactivation at -79 mV. This sodium current
      is reduced by agents that increase intracellular adenosine 3',5'-cyclic
      monophosphate (cAMP) and activate cAMP-dependent protein kinase including
      isoproterenol, 8-bromo-cAMP, and isobutylmethylxanthine. The phenylalkylamine
      desmethoxyverapamil blocks the TTX-insensitive sodium current in MCM1 cells in
      both tonic and use-dependent fashion. Membrane depolarization enhances this
      block. It is proposed that the TTX-insensitive sodium current in these cells may
      be similar in origin to the embryonic type of TTX-insensitive sodium current
      described in other cardiac and skeletal muscle preparations.

PMID- 1372483
TI  - Regulation of the purine salvage pathway in rat liver.
AB  - The regulation of purine metabolism in rat liver has been examined under
      conditions that alter the flux through the pathway. Rats were given
      intraperitoneal injections of ethanol, sodium acetate, or sodium phosphate to
      attain body water concentrations of approximately 70, 20, and 10 mM,
      respectively. The livers were freeze-clamped after 30 min, and extracts were made
      for the analysis of metabolites, cofactors, purine bases, and nucleosides;
      homogenates were made for the measurement of the activities and kinetic
      parameters of seven enzymes that participate in purine salvage. The values of the
      equilibrium constants of nine reactions were determined in vitro and compared
      with the ratios of the reactants measured in liver. The changes in
      phosphoribosylpyrophosphate (PRPP), a key intermediate in both the de novo and
      salvage pathways of purine metabolism, were directly correlated with the changes
      in ribose 5-phosphate (ribose-5-P); ([PRPP] = 1.7[ribose-5-P] - 7.4 mumol/kg).
      Ribose-5-P concentrations in turn could be predicted from the liver content of
      fructose 6-phosphate and glyceraldehyde 3-phosphate by calculation from the known
      equilibria. The maximum velocities in the tissue of the seven enzymes measured
      were calculated from the measured substrate values in the liver and with
      consideration of other effectors of enzyme activity. PRPP synthetase was the
      least active of the enzymes measured, indicating a possible rate-limiting step.
      The delta G of the enzyme steps differed from equilibrium values by factors
      ranging from 4 (nucleoside phosphorylase) to 10(5) (PRPP synthetase and purine
      transferase reactions). The regulation of purine salvage appeared to depend on
      the levels of PRPP and ribose-5-P.

PMID- 1372482
TI  - cAMP-stimulated ion currents in Xenopus oocytes expressing CFTR cRNA.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in
      stage V/VI Xenopus oocytes by injection of cRNA transcribed in vitro from a
      pBluescript vector containing 6.2-kb wild-type cDNA. This clone was also used for
      the preparation of antisense RNA. Double-electrode voltage clamp was employed to
      measure transmembrane currents. In sense RNA-injected oocytes, cAMP depolarized
      the membrane potential (Vm) from -52 to -31 mV and increased membrane conductance
      (Gm) 10-fold. However, cAMP had no effect on Vm or Gm in uninjected oocytes or in
      oocytes injected with antisense RNA. The endogenous Ca-activated Cl currents of
      control oocytes were abolished by 4,4'-diisothiocyanostilbene-2,2'-disulfonic
      acid (DIDS; 50 microM) or bath Cl replacement. In contrast, the cAMP-stimulated
      currents of CFTR-expressing oocytes were DIDS insensitive and were inhibited only
      approximately 50% when bath Cl was replaced by gluconate or glutamate. In
      addition, the Cl channel blockers 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB;
      50 microM) and diphenylamine-2-carboxylic acid (DPC; 3 mM) reduced the cAMP
      evoked currents by only approximately 10%. The stimulated currents of CFTR
      expressing oocytes were reduced approximately 30% by 10 mM Ba, suggesting that
      the Cl-independent current component is due to an increase in K conductance. Our
      results indicate that expression of CFTR in Xenopus oocytes produces a cAMP
      activated Cl current. The Cl-independent current may represent a regulatory
      action of CFTR on K conductance pathways or a secondary response of the oocyte
      membrane to the high Cl conductance induced by CFTR expression.

PMID- 1372484
TI  - Effects of chloroquine and methylamine on lysosomal enzyme secretion by rat
      pancreas.
AB  - In vivo pancreatic secretion of the lysosomal hydrolase cathepsin B was found to
      be increased by infusion of the secretagogue caerulein. The basal as well as
      caerulein-stimulated in vivo rate of cathepsin B was further increased by
      infusion of either chloroquine or methylamine while neither the basal nor the
      secretagogue-stimulated rates of amylase secretion were altered by the
      lysosomotropic agents. These observations indicate that neutralization of the
      acidic prelysosomal compartment by administration of lysosomotropic agents
      results in lysosomal enzyme entry, by default, into the regulated secretory
      pathway. In vitro stimulation of pancreatic acini with caerulein was also found
      to stimulate cathepsin B secretion. That in vitro rate of cathepsin B secretion
      stimulated by caerulein was not increased in acini prepared from animals infused
      with caerulein, chloroquine, or methylamine, but the in vitro rate of cathepsin B
      secretion stimulated by caerulein was increased in acini prepared from animals
      infused with caerulein plus either chloroquine or methylamine. Under these
      conditions, redistribution of cathepsin B from the lysosome-enriched to the
      zymogen granule-enriched subcellular fraction was noted, and lysosomal enzyme
      containing organelles became increasingly fragile. These observations indicate
      that in vivo secretagogue stimulation increases the degree of diversion of
      lysosomal hydrolases into the regulated secretory compartment when the
      prelysosomal compartment has been neutralized with lysosomotropic agents.

PMID- 1372485
TI  - Adenosine A1 receptors mediate inhibition of tachykinin release from perifused
      enteric nerve endings.
AB  - A perifused preparation of guinea pig myenteric nerve varicosities (synaptosomes)
      was used to determine the characteristics of evoked tachykinin release and the
      inhibition of such release by adenosine analogues. Release of substance P-like
      immunoreactivity (SP-LI) and neurokinin A-like immunoreactivity (NKA-LI) was
      evoked by elevated extracellular [K+] in a reversible and repeatable manner. This
      release was completely abolished in the absence of extracellular Ca2+. Perifusion
      in the presence of 5'-N-ethylcarboxamidoadenosine (NECA), a nonselective A1/A2
      adenosine receptor agonist, decreased K(+)-evoked release of SP-LI and NKA-LI
      compared with that in the absence of the nucleoside. Similar decrements in
      peptide release were obtained with N6-cyclopentyl adenosine (CPA), a selective A1
      agonist, and 2-[p-(2-carboxyethyl)]phenethylamino-5'-N-ethyl-carboxamidoadenosi
      ne (CGS 21680), a selective A2 agonist. Response to all nucleosides was graded.
      Potency order of adenosine analogues was CPA greater than NECA much greater than
      CGS 21680. Inhibition due to the nucleosides was diminished in the presence of
      the highly selective A1-receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine
      (DPCPX) while perifusion in the presence of DPCPX alone did not alter evoked
      release of either peptide. These findings provide direct measurements of
      inhibitory effects of adenine nucleosides on the release, from enteric nerve
      endings, of endogenous neuromediators SP and NKA. The findings also directly
      demonstrate the presence of functional adenosine receptors of the A1 subtype on
      enteric nerve endings coupled negatively to release of tachykinins. The presence
      of A2 receptors on enteric nerve endings is neither supported nor excluded.

PMID- 1372486
TI  - Developing bronchopulmonary epithelium of the human fetus secretes fluid.
AB  - We studied human fetal lung tissue in submersion organ culture to determine
      whether the bronchopulmonary epithelium secretes fluid during development. In
      this system the acinar tubules continued to grow, secrete fluid, and become
      progressively dilated. Baseline transepithelial potential differences (psi t) of 
      0.5 to -11 mV (mean, -3.8 mV, lumen negative, n = 27) were measured with
      microelectrodes after 3-8 days in culture, suggesting active electrolyte
      transport. Bumetanide (500 microM), an inhibitor of chloride secretion in other
      systems, decreased the basal psi t from -5 +/- 1.5 to -3.2 +/- 1.6 (SE) mV (P
      less than 0.05, n = 6), suggesting that chloride transport contributed to the
      voltage. Isoproterenol (5 microM) increased the baseline psi t from -5.6 +/- 2.1
      to -9.2 +/- 2.5 (SE) mV (P less than 0.05, n = 4). Subsequent addition of
      bumetanide inhibited the isoproterenol-induced stimulation of the psi t by 20% (P
      less than 0.05). 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate. (CPT
      cAMP, 50 microM) and 3-isobutyl 1-methylxanthine (IBMX, 100 microM) had similar
      effects, causing an increase in the psi t from -2.2 +/- 0.5 to -8 +/- 1.6 (SE)
      mV, an effect that was inhibited by the addition of bumetanide (P less than
      0.005, n = 6). Both isoproterenol and CPT-cAMP/IBMX produced significant
      increases in the percentage luminal area of the explants at 12 and 24 h after
      exposure compared with control. We conclude that 1) the developing
      bronchopulmonary epithelium (acinar tubules) contributes to lung fluid production
      in the human fetus, 2) fetal lung fluid secretion is chloride dependent, and 3)
      chloride secretion and fluid secretion may be stimulated by a beta-agonist and
      cAMP.

PMID- 1372488
TI  - Biological activities and potential therapeutic uses of steel factor. A new
      growth factor active on multiple hematopoietic lineages.
AB  - Recently, a novel growth factor has been cloned that has growth promoting
      activities on a wide variety of hematopoietic cell lineages. This factor has been
      referred to as mast cell growth factor, stem cell factor, or kit ligand, and will
      be referred to here as steel factor. Steel factor stimulates the growth of cells
      via its interaction with the c-kit proto-oncogene, which is a tyrosine kinase
      receptor that is expressed on the surface of a number of different cell types. In
      addition to its effects on hematopoiesis, this factor also plays a role in the
      development of melanocytes and germ cells. The discovery of this growth factor
      provided the final piece of the puzzle to explain the molecular defects
      associated with several well known genetic mutations in mice, and has opened the
      door to understanding the role of this factor in development. Similar genetic
      defects may exist in humans as well. The aim of this paper is to review the
      biological structure and activities of this new growth factor, and to discuss its
      potential applications in clinical medicine.

PMID- 1372487
TI  - Large conducting potassium channel reconstituted from airway smooth muscle.
AB  - Microsomal fractions were prepared from canine and bovine airway smooth muscle
      (ASM) by differential and gradient centrifugations. Surface membrane vesicles
      were characterized by binding assays and incorporated into planar lipid bilayers.
      Single-channel activities were recorded in symmetric or asymmetric K+ buffer
      systems and studied under voltage and Ca2+ clamp conditions. A large-conductance
      K(+)-selective channel (greater than 220 pS in 150 mM K+) displaying a high Ca2+,
      low Ba2+, and charybdotoxin (CTX) sensitivity was identified. Time analysis of
      single-channel recordings revealed a complex kinetic behavior compatible with the
      previous schemes proposed for Ca(2+)-activated K+ channels in a variety of
      biological surface membranes. We now report that the open probability of the
      channel at low Ca2+ concentration is enhanced on in vitro phosphorylation, which
      is mediated via an adenosine 3',5'-cyclic monophosphate-dependent protein kinase.
      In addition to this characterization at the molecular level, a second series of
      pharmacological experiments were designed to assess the putative role of this
      channel in ASM strips. Our results show that 50 nM CTX, a specific inhibitor of
      the large conducting Ca(2+)-dependent K+ channel, prevents norepinephrine
      transient relaxation on carbamylcholine-precontracted ASM strips. It was also
      shown that CTX reversed the steady-state relaxation induced by vasoactive
      intestinal peptide and partially antagonized further relaxation induced by
      cumulative doses of this potent bronchodilatator. Thus it is proposed that the
      Ca(2+)-activated K+ channels have a physiological role because they are
      indirectly activated on stimulation of various membrane receptors via
      intracellular mechanisms.

PMID- 1372489
TI  - Suppressor cytokines and regulation of myelopoiesis. Biology and possible
      clinical uses.
AB  - A number of biologically active and biochemically well-characterized cytokines
      have been shown to have either direct or indirect suppressive activities on the
      proliferation/differentiation of myeloid stem/progenitor cells. This article is a
      brief review of the actions of some of these molecules. These molecules include H
      subunit ferritin, macrophage inflammatory protein-1 alpha, the interferons-alpha,
      -beta, and -gamma, the tumor necrosis factors-alpha and -beta (lymphotoxin),
      prostaglandins, E1 and E2, inhibin, transforming growth factor-beta, and
      lactoferrin. I will also review the actions of other suppressor molecules,
      including a newly identified 8-kd molecule that has not yet been sequenced and a
      synthetic pentapeptide. Current information is given on the in vitro actions of
      these molecules together with their activity in vivo in animal models.
      Possibilities for their clinical use are discussed.

PMID- 1372490
TI  - Effect of Bay K 8644 on the magnitude of isoflurane and halothane contracture of
      skeletal muscle from patients susceptible to malignant hyperthermia.
AB  - Isoflurane has a lesser ability than halothane to induce contracture in malignant
      hyperthermia (MH) muscle in vitro. This does not necessarily imply that
      isoflurane is not as potent an MH trigger as halothane in vivo. A hypothesis was
      tested that in vitro treatment with Bay K 8644, an activator of both the
      dihydropyridine receptors as well as the sodium channels of the T-tubules,
      potentiates isoflurane-induced MH-susceptible skeletal muscle contracture. In
      addition to the usual halothane-caffeine test, other muscle bundles were exposed
      to 10 microM Bay K 8644-halothane and equipotent anesthetic concentrations
      (expressed in multiple minimum alveolar concentration [MAC]) of isoflurane either
      alone or combined with Bay K 8644. In 14 MH-susceptible muscle bundles, the mean
      maximum contracture induced by 2 MAC isoflurane was 0.20 +/- 0.22 g (mean +/-
      SD), and this value was significantly less than that obtained with 2 MAC
      halothane (0.68 +/- 0.40 g). Bay K 8644 did not induce muscle contracture on its
      own but consistently enhanced both the 0.5 MAC isoflurane and halothane to the
      same maximal isometric tension (1.09 +/- 0.35 g and 1.11 +/- 0.37 g,
      respectively). Such an effect was not observed in the MH-nonsusceptible group.
      Under the conditions of this in vitro study, 0.5 MAC isoflurane appears to be as
      potent as halothane in inducing muscle contracture in skeletal muscle bundles
      from individuals susceptible to MH.

PMID- 1372491
TI  - Tradition, rationality, and power in introductory nursing textbooks: a critical
      hermeneutics study.
AB  - This study investigated the language used to describe, explain, and interpret the
      concept of nursing process in four introductory nursing textbooks. A critical
      theory framework was used to reinterpret the ways in which language or linguistic
      activities construct the social-historical reality of nurses. Themes related to
      tradition, rationality, and power relationships were explicated. The meanings
      disclosed from the world of the text provide understandings about how nurses
      interpret their professional autonomy and how normative structures inform what
      constitutes authority and responsibility in research, education, and practice.

PMID- 1372492
TI  - Structural domains of the extracellular domain of human nerve growth factor
      receptor detected by partial proteolysis.
AB  - Using partial proteolytic cleavage, the nerve growth factor (NGF) binding site
      and the epitopes for two anti-NGF receptor (NGFR) monoclonal antibodies were
      localized on the recombinant extracellular domain (RED) of the NGFR. The RED was
      prepared in the baculovirus-insect cell system and was purified by immunoaffinity
      and ion-exchange chromatography. The four cysteine-rich repeat domains and some
      additional C-terminal sequences were resistant to proteolysis with papain or
      proteinase K. The Mr 32,000 papain-resistant fragment (P32) and the Mr 30,000
      proteinase K-resistant fragment (K30) share the same N terminus as the intact RED
      and have C termini in the vicinity of residue 170. Even though P32 and K30 have
      the same N terminus and probably differ by only a small number of amino acids at
      the C terminus, P32, but not K30, binds 125I-NGF. As judged by Western blot
      analysis, two anti-NGFR antibodies (ME20.4 and NGFR5) bind to P32 but have a
      lesser affinity for K30. Since antibody ME20.4 inhibits NGF binding but antibody
      NGFR5 does not, these antibodies bind to distinct epitopes. However, these
      epitopes apparently are closely spaced since these antibodies compete with each
      other for binding to biotinylated RED. NGF, but not the control protein
      cytochrome c, protects RED from papain digestion. Therefore, the P32 C terminus
      is important for the expression of the NGF binding site and the antibody-defined
      epitopes, even though the NGF binding site and antibody-defined epitopes probably
      are not encoded by the P32 C terminus. These data suggest that complex
      interactions occur between different regions of the RED, and that optimum NGF
      binding requires the integrity of multiple RED domains, including a short
      sequence to the C terminus of residue 170.

PMID- 1372493
TI  - Detection and separation of two kinds of acidic arginine amidases from boar sperm
      using lima bean trypsin inhibitor and aprotinin affinity adsorptions.
AB  - Two kinds of acidic arginine amidase activity were found in boar sperm. One
      enzyme was separated by a treatment consisting of lima bean trypsin inhibitor
      (LBTI) affinity adsorption and elution. The other enzyme was separated by
      aprotinin affinity adsorption and elution through the same solutions as those
      used for first enzyme; the two enzymes provisionally named boar sperm acidic
      arginine amidases 1 (BSAA-1) and 2 (BSAA-2), respectively. The amidolytic
      activity of BSAA-1 was increased by high concentrations of calcium chloride,
      while the activity of BSAA-2 was independent of calcium chloride. Their behavior
      with LBTI and aprotinin, and profiles of their substrate specificities, were also
      different. The affinity of LBTI to BSAA-1 was approximately 14 times higher than
      that to BSAA-2.

PMID- 1372494
TI  - Low serotonin and dopamine metabolite concentrations in cerebrospinal fluid from
      bulimic patients with frequent binge episodes.
AB  - Cerebrospinal fluid neurotransmitter metabolite levels were studied to assess
      whether measures of central serotonin, dopamine, or norepinephrine function are
      associated with severity of abnormal eating patterns in patients with bulimia
      nervosa. In comparison with healthy controls (N = 17), hospitalized bulimic
      patients with a history of binge eating more frequently than twice daily (N = 11)
      had significantly lower CSF concentrations of 5-hydroxyindoleacetic acid and
      homovanillic acid. For the total patient group (N = 29), levels of both
      metabolites were significantly inversely correlated with binge frequency. On the
      basis of preclinical studies, these results were examined in the context of
      speculative models in which low central serotonin function might contribute to
      blunted satiety responses in bulimic patients, while low central dopamine
      activity might play a role in abnormal hedonic responses to food.

PMID- 1372495
TI  - Lymphadenectomy in gastric carcinoma. A prospective and prognostic study.
AB  - In 193 gastric resections for adenocarcinoma, lymphadenectomy was prospectively
      evaluated to quantify the number of lymph nodes and to identify prognostic
      factors. Overall, 7112 nodes (median, 36.8 per patient) were resected with 27.2%
      showing metastases. Most nodes were found in the perigastric region. The
      histologic type and site of the tumor did not influence the number of invaded
      nodes, but tumor stage and quality of the resection (curative/palliative) did. By
      multivariate analysis the tumor stage, curative vs palliative resections, and the
      number of metastatic lymph nodes in curative resections were independent
      prognostic factors. Patients with less than six metastatic nodes showed a
      survival not significantly different from that of patients with normal nodes.
      These patients may be well treated by surgery alone, but the other patients may
      require multimodal therapy to improve their prognosis.

PMID- 1372496
TI  - Human cytomegalovirus nuclear and cytoplasmic dense bodies.
AB  - One of the characteristic features of cytomegalovirus (CMV) replication is the
      formation of cytoplasmic dense bodies. Recent findings revealed similar
      structures also in the nuclei of CMV-infected cells. By transmission electron
      microscopy, immuno electronmicroscopy, and cytochemistry, we have studied the
      morphogenetic steps and macromolecular composition of both structures. Our
      results show that both structures contain DNA, RNA and viral antigenic proteins.
      Nuclear dense bodies are probably an expression of a stimulated cellular
      metabolism, while cytoplasmic dense bodies may represent the site where surplus
      cellular and viral molecules are stored before being eliminated.

PMID- 1372499
TI  - Subsystems that process both matter-energy and information. The boundary.

PMID- 1372497
TI  - Mode of neutralization of lactate dehydrogenase-elevating virus by polyclonal and
      monoclonal antibodies.
AB  - Neutralization of the infectivity of [3H]uridine-labeled lactate dehydrogenase
      elevating virus (LDV) by polyclonal mouse or rabbit antibodies to the envelope
      glycoprotein of LDV, VP-3, or by neutralizing monoclonal antibodies (mAb) that
      recognize a different epitope on VP-3 than the polyclonal antibodies correlated
      with an increase in the sedimentation rate of LDV from 230 S to greater than or
      equal to 270 S. Incubation of LDV with normal mouse plasma or non-neutralizing
      mAbs to LDV VP-3 had no effect on its sedimentation rate. Similarly, incubation
      of a neutralization escape variant of LDV with the mAb used in its selection had
      no effect on its sedimentation rate, whereas neutralization of this variant by
      polyclonal mouse or rabbit anti-VP3 antibodies increased the sedimentation rate.
      Neutralization of LDV infectivity was only observed at high antibody/virion
      ratios and often was followed by loss of the viral RNA. The results suggest that
      neutralization of LDV infectivity results from binding of multiple antibody
      molecules that recognize specific epitopes on the viral envelope glycoprotein and
      ultimately leads to disintegration of the virions.

PMID- 1372498
TI  - Hartmann's procedure for carcinoma of the rectum and sigmoid colon.
AB  - A review of the Hartmann's operation for patients with rectal and sigmoid cancer
      over an 18 year period is presented. There were 1063 patients who had a resection
      for carcinoma of the rectum or sigmoid colon and 4.4% of these had a Hartmann's
      procedure. This operation was particularly useful in the management of patients
      who presented with a proximal obstruction or perforation at the tumour site. It
      was also effective in the elective treatment of elderly unfit patients who had
      locally advanced tumours or those with distant metastases. Re-anastomosis is
      recommended in those patients who are relatively fit and have had a potentially
      curative resection.

PMID- 1372500
TI  - Heparin-binding fibronectin fragments containing cell-binding domains and devoid
      of hep2 and gelatin-binding domains promote human embryo fibroblast
      proliferation.
AB  - The proliferation promoting activity of various proteolytic fragments of human
      plasma fibronectin was assayed. Study of this activity in fragments, purified by
      affinity chromatography, has shown that only heparin-binding fragments were
      capable of promoting fibroblast proliferation while gelatin- and fibrin-binding
      fragments were not. Heparin-binding fragments with high affinity for heparin were
      characterized by high activity levels while those with low heparin affinity were
      inactive. Heparin-binding fragments with the highest proliferation promoting
      activity contained the cell-binding domain and were virtually devoid of the hep2,
      hep1 and gelatin-binding domains.

PMID- 1372501
TI  - Differential regulation of the imipramine-sensitive serotonin transporter by cAMP
      in human JAr choriocarcinoma cells, rat PC12 pheochromocytoma cells, and C33-14
      B1 transgenic mouse fibroblast cells.
AB  - The imipramine-sensitive serotonin transporter appears to be the receptor for
      clinically important antidepressants. Some studies suggest that this protein may
      fall under the influence of abnormal and as yet uncharacterized regulatory
      effects during depressive illness. Despite these putative disease-related
      effects, regulation has never been demonstrated in either the platelet or
      synaptosome model systems. Here we demonstrate for the first time that the
      imipramine-sensitive serotonin transport activity in either JAr choriocarcinoma
      or PC12 pheochromocytoma cell lines is subject to regulation by cAMP.
      Unexpectedly, the regulatory effect is opposite in the two cases, causing
      stimulation in JAr (increased Vmax) and inhibition in PC12 (kinetically complex).
      Appearance of these kinetic effects lagged 15 to 20 hours behind peak cAMP
      levels. The results are consistent with the interesting possibility that
      different tissues may express isoforms of the recently cloned serotonin
      transporter cDNAs. We suggest, therefore, that JAr and PC12 are attractive models
      in which to pursue detailed analysis of serotonin transport and its manner of
      regulation by cAMP.

PMID- 1372502
TI  - Glycosulfatase activity of Helicobacter pylori toward gastric mucin.
AB  - A glycosulfatase activity toward sulfated gastric mucus glycoprotein was
      identified in the extracellular material elaborated by H. pylori, a bacteria
      implicated in the etiology of gastric disease. Upon acetone precipitation, an
      active enzyme fraction at 64% acetone was obtained which on SDS-PAGE gave a major
      30kDa protein band. The H. pylori glycosulfatase exhibited maximum activity
      (314.8 pmol/mg protein/h) at pH 5.7 in the presence of Triton X-100 and CaCl2,
      and was capable of removal of the sulfate ester groups situated at C-6 of N
      acetylglucosamine, galactose and glucose. However, the enzyme was ineffective
      toward galactosylceramide and lactosylceramide sulfates which contain the sulfate
      ester group on C-3 of galactose. The results suggest that H. pylori is capable of
      overcoming the interference by sulfated mucus glycoprotein with its colonization
      of gastric mucosa.

PMID- 1372503
TI  - Propidium iodide staining correlates with the extent of DNA degradation in
      isolated nuclei.
AB  - Gradual degradation of internucleosomal DNA is a hallmark of apoptosis and can be
      simulated by incubating isolated thymocyte nuclei in the presence of 5 mM Mg2+
      and 5 mM Ca2+ at 37 degrees C. Staining of nuclei with the DNA binding
      fluorescent dye propidium iodide (PI) showed that intensity of fluorescence
      correlated with the extent of DNA degradation. PI fluorescence was increased in
      the presence of DNase I. Thus it seems that the cleavage of chromatin DNA by
      DNase 1 or by the endogenous enzyme increases the accessibility of DNA for the
      dye. No increase of fluorescence was observed in the presence of the known
      inhibitors of the endogenous endonuclease: Zn2+ and EGTA. However, the presence
      of Zn2+ led to decreased staining of the nuclei by PI and caused a shift in the
      scatter profile of the nuclei, suggesting that a conformational change of
      chromatin is induced by this ion. This correlation between intensity of PI
      staining and DNA degradation should be useful to compare endogenous nuclease
      levels in lymphocyte populations.

PMID- 1372504
TI  - Absence of a putative ATP/GTP binding site in the rat prolactin receptor.
AB  - Two types of the long form of the rat prolactin receptor have been identified by
      two independent groups. One type of receptor has a consensus sequence for a
      putative ATP/GTP binding site in the cytoplasmic domain, while the other does
      not. Since this site would confer kinase activity to the prolactin receptor and
      represent an important element in the process of signal transduction, we wanted
      to clarify this discrepancy. To that end, three procedures capable of detecting a
      point mutation were performed: Southern analysis of reverse transcribed
      polymerase chain reaction (PCR) products, allele-specific PCR, and S1 nuclease
      analysis. All results clearly indicated that the sequence for the putative
      ATP/GTP binding site does not exist in the prolactin receptor.

PMID- 1372505
TI  - Verapamil blocks basal and angiotensin II-induced RNA synthesis of rat aortic
      vascular smooth muscle cells.
AB  - We evaluated VER effect on RNA synthesis of quiescent and angiotensin II (AII)-
      stimulated cultured rat aortic vascular smooth muscle cells (VSMC). In a dose
      dependent manner, VER decreased [3H]uridine uptake by quiescent VSMCs (ED50 7 x
      10(-6)M), an effect that was shared by other calcium antagonists, but to a
      variable degree. VER caused a significant effect within 3 hours and attained a
      maximal effect at 7 hours. In addition VER caused a 22 +/- 2% decrease in
      [3H]uridine uptake by VSMCs stimulated with 10% fetal bovine serum, while it
      completely abolished [3H]uridine uptake by VSMCs induced by AII. We conclude that
      VER decreases basal and inhibits AII-induced increase in mRNA synthesis of VSMCs.
      These data may explain in part how VER causes a decrease in vascular resistance
      and alters the vasoconstrictor effect of AII.

PMID- 1372506
TI  - Tyrosine phosphorylation and its possible role in superoxide production by human
      neutrophils stimulated with FMLP and IgG.
AB  - Superoxide production by human neutrophils stimulated with FMLP and soluble
      aggregated human IgG were inhibited in a dose dependent manner by two kinds of
      tyrosine kinase inhibitors, erbstatin and genistein. Superoxide production
      stimulated with surface bound IgG, however, was scarcely inhibited by either
      inhibitor. Protein tyrosine phosphorylation studies with immunoblotting revealed
      specific tyrosine phosphorylation of a 40 Kd protein by soluble aggregated and
      surface bound IgG, and that of a 39 Kd protein, as well as the 40 Kd protein, by
      FMLP. These were all inhibited by the tyrosine kinase inhibitors. These data
      suggest that superoxide production induced by FMLP and soluble aggregated IgG
      are, at least in part, tyrosine kinase dependent, but the tyrosine kinases and/or
      substrates of tyrosine kinases involved may be different. In addition, tyrosine
      kinase independent pathways are also suggested to be involved in superoxide
      production by stimulation with surface bound IgG.

PMID- 1372507
TI  - Molecular cloning of a cDNA encoding a novel member of the mouse glutamate
      receptor channel family.
AB  - The primary structure of a novel putative subunit of the mouse glutamate receptor
      channel, designated as delta 1, has been deduced by cloning and sequencing the
      cDNA. The delta 1 subunit shows 21-25% amino acid sequence identity with
      previously characterized rodent glutamate receptor channel subunits and thus may
      represent a new subfamily of the glutamate receptor channel.

PMID- 1372508
TI  - Premature rupture of the membranes: effect of penicillin prophylaxis and long
      term outcome of the children.
AB  - To assess the value of prophylaxis with penicillin in women with premature
      rupture of membranes (PROM) and the long-term outcome of children born after
      prolonged PROM, we studied 221 women with this condition. Penicillin (5 mu twice,
      6 hours apart) was given intravenously to 50 women and placebo to 51 women,
      whereas 76 comparable patients were treated without penicillin or placebo. The
      time interval between PROM and delivery ranged from 14 hours to 56 days.
      Chorioamnionitis occurred more frequently (p less than 0.05) among patients with
      placebo (14%) than among those treated with penicillin (2%). One puerperal
      endometritis appeared in the placebo group compared with none in the penicillin
      group. One newborn (1.7%) born to a mother with placebo prophylaxis developed
      septicemia, compared with none in the penicillin group. The outcomes of
      pregnancies complicated with PROM treated without penicillin or placebo were
      comparable with those in the placebo group. In addition, we compared somatic and
      psychomotor development of 159 children born to mothers with prolonged PROM (more
      than 12 hours; mean, 5.6 days; range, 14 to 1344 hours) with those of 43 children
      born at similar gestational age within 5 hours after PROM. No pulmonary sequelae
      could be linked to the long time period between PROM and delivery, but infants
      born soon after PROM more often (p less than 0.05) had cerebral palsy (8 of 43,
      18.6%) than did infants born after prolonged PROM (7 of 159; 4.4%). We conclude
      that, in cases with PROM, penicillin prophylaxis decreases maternal and neonatal
      infectious morbidity and that the long interval between PROM and delivery does
      not impair the long-term outcome for these children.

PMID- 1372509
TI  - Cultivation of mammalian cells on macroporous microcarriers.
AB  - Adherent cells can be cultivated in a stirred-tank bioreactor by attaching to
      microcarriers. Macroporous microcarriers, with their intraparticle space and
      surface area for cell growth, can potentially support a higher cell concentration
      than conventional microcarriers, which support cell growth only on the external
      surface. Chinese hamster ovary (CHO) cells and green monkey kidney (Vero) cells
      were cultivated on macroporous microcarriers, Cultispher-G. Cells attached to the
      microcarriers at a slow rate and grew to a high density. Thin sections of the
      microcarriers demonstrate that cells were initially on the exterior of the
      microcarriers and migrated into the interior as cell concentration increased.
      Vero cells cultivated on these microcarriers were successfully used for the
      production of vesicular stomatitis virus (VSV).

PMID- 1372510
TI  - P0 promoter directs expression of reporter and toxin genes to Schwann cells of
      transgenic mice.
AB  - We generated transgenic mice that specifically express foreign genes in
      myelinating Schwann cells. A 1.1 kb segment of 5' flanking sequence from the rat
      P0 gene was used to drive expression of the genes encoding human growth hormone
      (hGH) and bacterial diphtheria toxin A chain (DT-A). The P0-hGH mice expressed
      hGH in myelinating Schwann cells, but not in nonmyelinating Schwann cells, the
      central nervous system, or any other tissue assayed. This expression was
      activated on a developmental schedule comparable to that of endogenous myelin
      gene expression. One line of P0-DT-A mice developed a generalized hypomyelinating
      peripheral neuropathy, with Schwann cell deficiency apparent in newborn animals.
      Peripheral nerves from adult mice of this line displayed morphological
      alterations ranging from completely denuded axons to myelinated Schwann cells
      undergoing degeneration, although occasional Schwann cells were able to form
      apparently normal myelin sheaths. Pronounced secondary changes, including
      proliferation and retraction of processes, occurred in the nonmyelinating Schwann
      cells of these P0-DT-A mice.

PMID- 1372512
TI  - A bispecific antibody detects cytotoxic T lymphocytes of unknown antigen
      specificity in patients with granular lymphocyte-proliferative disorders.
AB  - A simple and sensitive method for the detection of cytotoxic T lymphocytes (CTL)
      of unknown antigen specificity was investigated. Using anti-CD3 Fab' x anti-CD10
      Fab' bispecific antibody or intact anti-CD3 monoclonal antibody, we induced
      cytotoxicity for CD10+, Fc gamma receptor-positive Daudi target cells in
      peripheral blood mononuclear cells (PBMC) obtained from patients with granular
      lymphocyte-proliferative disorders (GLPD). The results indicated that the
      bispecific antibody was much more efficient than the intact anti-CD3 monoclonal
      antibody in inducing cytotoxicity. Since CD3+CD4-CD8+ granular lymphocytes in
      patients with GLPD are considered to be in vivo-primed CTL of unknown antigen
      specificity, this bispecific antibody method may be useful for detecting in vivo
      primed CTL within PBMC. By using this bispecific antibody, it will be possible to
      detect circulating in vivo-primed CTL in other clinical conditions.

PMID- 1372511
TI  - Characterization of a second human pulmonary surfactant-associated protein SP-A
      gene.
AB  - Pulmonary surfactant is a lipid-protein complex involved in maintaining alveolar
      stability. SP-A is the major surfactant-associated protein of 26 to 38 kD. A
      human SP-A gene (SP-A I) and two distinct SP-A cDNAs, MPSAP 1A and MPSAP 6A, have
      been reported previously. We have isolated and characterized a second human SP-A
      gene (SP-A II), which appears to code for the mRNA corresponding to the
      previously described MPSAP-1A cDNA. Both genes consist of five exons, a consensus
      recognition sequence for initiation, TATAAA, and a polyadenylation signal
      sequence. Significant divergence in the two genes is observed throughout. The
      divergence is highest in the upstream region, intron I, exon III, and noncoding
      portion of exon V. The coding regions of all other exons and the introns show
      much lower divergence. Transcripts from both genes were found in adult human
      lung, using gene-specific oligonucleotide probes in Northern blot analysis.

PMID- 1372513
TI  - Surgical glove perforation and maxillofacial trauma: to plate or wire?
AB  - The technique of interdental wiring was compared with a small-plate
      osteosynthesis technique (SPO) in a prospective study of surgical glove
      perforations acquired during the treatment of mandibular fractures. Using the SPO
      technique there was a significant reduction in the incidence of skin penetrating
      injuries in the surgeon (P less than 0.005) and assistant surgeon groups (P less
      than 0.05). The reduction in the incidence of glove perforation in the assistant
      surgeon group was very highly significant in the SPO series (P less than 0.001).
      The reduction in the surgeon group was not significant. No difference was noted
      in the scrub nurse group. The small-plate osteosynthesis technique has the
      advantage of reducing the risk of intraoperative cross-infection transmitted by
      hand contamination or penetrating injury. The recommended precautions for
      preventing the transmission of blood-borne pathogens are reviewed.

PMID- 1372514
TI  - Stable target-sensitive immunoliposomes.
AB  - Interaction of immunoliposomes composed of dioleoylphosphatidylethanolamine
      (DOPE) (80%), dioleoylphosphatidic acid (DOPA) (20%), and a small amount of
      specific antibody with Herpes Simplex virus (HSV) were studied by detecting the
      immune-dependent lysis of liposomes. DOPA was used as the principal stabilizer of
      the immunoliposomes. Antibodies conjugated with N
      glutarylphosphatidylethanolamine or oxidized GM1 served as the target-specific
      ligands of immunoliposomes. These immunoliposomes (d = 160-180 nm) were stable
      for at least one month when stored at 4 degrees C. However, they undergo a rapid
      aggregation and lysis reaction in the presence of a membrane-bound target such as
      intact HSV virions. We have also employed epitope peptide-containing liposomes
      (target liposomes) to mimic the virus and showed that the immunoliposomes could
      be aggregated and lysed by the target liposomes in an antigen-dependent manner.
      Immunoliposome lysis could be accelerated by increasing the incubation
      temperature to 60-70 degrees C. No immunoliposome lysis was observed if the
      target liposomes were absent, indicating the prolonged stability of the
      immunoliposomes. Liposome lysis was always accompanied by liposome aggregation.
      However, the aggregation-induced liposome destabilization is unique to the HII
      phase-forming lipids such as DOPE. DOPC-containing immunoliposomes did not lyse
      despite the fact that massive liposome aggregation had taken place.

PMID- 1372515
TI  - Interaction of a substance P agonist and of substance P antagonists with lipid
      membranes. A thermodynamic analysis.
AB  - The molecular characteristics of the neuropeptide substance P (SP), its agonist
      [Sar9,Met-(O2)11]SP, and three of its antagonists [D-Arg1,D-Pro2,D
      Trp7,9,Leu11]SP, [D-Arg1,D-Trp7,9,Leu11]SP, and [D-Pro2,D-Trp7,9]SP were
      investigated at the air/water interface and when bound to lipid monolayers and
      bilayers. Measurement of the Gibbs adsorption isotherm showed that the surface
      areas of SP and its agonist (240 +/- 5 A2 at biologically relevant
      concentrations) were distinctly larger than those of the antagonists (138 +/- 5
      A2) [Seelig, A. (1990) Biochim. Biophys. Acta 1030, 111-118]. The surface
      activity of the peptides increased in the order [Sar9,Met(O2)11]SP less than SP
      less than [D-Pro2,D-Trp7,9]SP less than [D-Arg1,D-Trp7,9,Leu11]SP = [D-Arg1,D-
      Pro2,D-Trp7,9,Leu11]SP and correlated with the respective binding affinities to
      lipid membranes. The agonist did not insert into neutral and negatively charged
      bilayers or into densely packed lipid monolayers (at surface pressures greater
      than 31 mN/m). In contrast, the three antagonists gave rise to a strong binding
      both to neutral and to charged lipid monolayers and bilayers. The degree of
      binding was evaluated from the area increase of lipid monolayers upon peptide
      insertion, and the binding isotherms were analyzed in terms of the Gouy-Chapman
      theory. At the monolayer-bilayer equivalence pressure of approximately 32 mN/m,
      the binding can be described by a surface partition equilibrium with binding
      constants of (4.5 +/- 0.1) x 10(3) M-1 for [D-Pro2,D-Trp7,9]SP and (1.3 +/- 0.1)
      x 10(4) M-1 for both [D-Arg1,D-Trp7,9,Leu11]SP and [D-Arg1,D-Pro2,D
      Trp7,9,Leu11]SP for pure palmitoyloleoylphosphatidylcholine (POPC)
      membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372516
TI  - Binding of tachyplesin I to DNA revealed by footprinting analysis: significant
      contribution of secondary structure to DNA binding and implication for biological
      action.
AB  - In view of the cationic amphipathic structure of tachyplesin I and antiparallel
      beta-sheet as a general DNA binding motif, DNA binding of the antimicrobial
      peptide has been examined. Several footprinting-like techniques using DNase I
      protection, dimethyl sulfate protection, and bleomycin- (BLM-) induced DNA
      cleavage were applied in this study. Some distinct footprints with DNase I are
      detected, and also the sequence-specific cleavage mode of the BLM-Fe(II) complex
      clearly is altered in the presence of tachyplesin I. In addition, methylation of
      the N-7 residue of guanine situated in the DNA major groove is not entirely
      inhibited (or activated) by tachyplesin I. The results suggest that tachyplesin I
      interacts with the minor groove of DNA duplex. Disappearance of the footprints by
      dithiothreitol-treated tachyplesin I and Ala-tachyplesin strongly suggests a
      significant contribution of secondary structure containing an antiparallel beta
      sheet to the DNA binding of tachyplesin I. This is the first report on DNA
      interaction with a small peptide which contains a unique antiparallel beta-sheet
      structure. The mechanism for antimicrobial action of tachyplesin I has also been
      inferred.

PMID- 1372517
TI  - Identification of intermolecular RNA cross-links at the subunit interface of the
      Escherichia coli ribosome.
AB  - 32P-Labeled 70S ribosomes and polysomes were isolated from cultures of
      Escherichia coli and treated with the cross-linking reagent bis(2
      chloroethyl)methylamine. Intermolecular 16S-23S RNA cross-linked complexes were
      separated from other products of the cross-linking reactions by a two-step
      sucrose density gradient centrifugation procedure and subjected to
      oligodeoxynucleotide-directed partial nuclease digestions with RNase H. Cross
      linked RNA fragments released by such directed digests were resolved by two
      dimensional gel electrophoresis and analyzed using classical oligonucleotide
      fingerprinting techniques. Two distinct intermolecular cross-links between the
      16S and 23S RNA could be localized in this manner, involving positions 1408-1411
      and 1518-1520 in the 16S RNA sequence and positions 1912-1920 in the 23S RNA
      sequence. These data provide the first direct topographical links between the RNA
      of the 30S and 50S subunits in the functional ribosome and, together with
      previous topographical data concerning the three-dimensional folding of the rRNA,
      demonstrate that there is a tight cluster at the ribosomal interface both of
      sites implicated in ribosomal function and of posttranscriptionally modified
      nucleotides in the rRNA.

PMID- 1372518
TI  - Alteration in DNA cross-linking and sequence selectivity of a series of
      aziridinylbenzoquinones after enzymatic reduction by DT-diaphorase.
AB  - DT-diaphorase (DTD) mediated reduction of a series of 2,5-bis-substituted-3,6
      diaziridinyl-1,4-benzoquinones was found to increase the level of DNA interstrand
      cross-linking (ISC) formed at neutral pH with an enhancement observed as the pH
      was decreased to 5.8. The analogues used were symmetrically alkyl-substituted
      carbamoyl ester analogues of AZQ (D1-D7), 3,6-diaziridinyl-1,4-benzoquinone
      (DZQ), the 2,5-dimethyl derivative (MeDZQ), and a 2,5-bis[(2-hydroxyethyl)amino]
      analogue (BZQ). At pH 5.8, the level of DNA ISC induced by enzymatic reduction
      was as follows: DZQ greater than MeDZQ much greater than D1 (methyl) greater than
      D3 (n-propyl) greater than D2 (AZQ; ethyl) greater than D5 (n-butyl) greater than
      D7 (sec-butyl) greater than D4 (isopropyl) D6 greater than (isobutyl). A similar
      trend was observed at pH 7.2. The level of DNA ISC induced by BZQ, which is not a
      substrate for DTD, was not increased by enzymatic reduction. Dicumarol, a known
      inhibitor of DTD, was capable of inhibiting the DNA ISC induced by these quinones
      upon enzymatic reduction. MeDZQ and DZQ reacted with guanines, as measured by
      Maxam and Gilbert sequencing, with a sequence selectivity similar to that of the
      nitrogen mustard class of antitumor agents. Enzymatic reduction of DZQ and MeDZQ
      by DTD was found to alter their sequence-selective alkylation. Reduced DZQ showed
      enhanced guanine alkylation in 5'-GC-3' sequences and new sites of adenine
      alkylation in 5'-(A/T)AA-3' sequences. Reduced MeDZQ only showed new sites of
      adenine alkylation at 5'-(A/T)AA-3' sequences but no enhancement of guanine
      alkylation. The new sites of adenine alkylation were found to be inhibited in the
      presence of magnesium and rapidly converted into apurinic sites.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1372519
TI  - Halide permeation through 10 pS and 20 pS anion channels in human airway
      epithelial cells.
AB  - Halide permeability sequences were obtained from reversal potential measurements
      of single-channel currents through 10 pS and 20 pS anion channels in human airway
      epithelial cells. The sequences obtained were Cl- greater than I- greater than Br
      greater than or equal to F- for the 10 pS channel and Cl- greater than I-
      greater than or equal to Br- greater than or equal to F- for the 20 pS channel.
      However, the permeability differences were not large, the greatest being 0.66 for
      the ratio of fluoride to chloride permeability in the 20 pS channel. Single
      channel currents were also measured with solutions of constant halide
      concentration but varying ratios of chloride to fluoride ions. An anomalous mole
      fraction effect was observed for the 20 pS channel but not for the 10 pS channel,
      suggesting that the former is a multi-ion channel. Comparison of the halide
      permeability sequences of these two channels with those of whole-cell currents in
      other epithelial cells does not support their involvement in any of the known
      whole-cell epithelial currents.

PMID- 1372520
TI  - Mammalian homeobox genes in normal development and neoplasia.
AB  - This review aims at providing an evaluation of the currently available data
      concerning the role of homeobox genes in mammalian embryonic pattern formation,
      and their involvement in oncogenic processes. The literature dealing with mouse
      and human homeobox genes is covered, with some excursions into Xenopus and
      chicken work because studies regarding particular aspects of development in the
      latter systems often complement those in mammals. Other studies in amphibians,
      chicken, and fish are omitted as they fall outside the scope of this survey
      devoted to mammalian genes. Emphasis is placed on expression and regulation
      during normal embryogenesis, on present hypotheses regarding gene function, on
      effects on development of modifying the expression patterns, and on observed
      aberrations in structure or expression associated with and possibly causally
      linked to neoplasia. The studies specifically dealing with the structure of the
      homeodomain and the mechanism of its interactions with DNA, which have been
      recently reviewed, are not considered here. The most thoroughly studied mammalian
      homeobox genes bear sequence homology to the Drosophila Antennapedia (Antp)
      homeotic gene and are thought to be involved in determination of regional
      identity along the anteroposterior (A-P) axis. Studies on these genes, the HOX
      genes, are oftem compared with related investigations in flies. In addition to
      the HOX genes, a number of genes containing a homeobox related to that in other
      Drosophila developmental control genes have been isolated from the mammalian
      genome and are being intensively studied. Homeodomains divergent from the Antp
      prototype have been discovered in an increasing number of transcription factors.
      Some of these may play a crucial role in local pattern formation, while others
      are tissue-specific or ubiquitous transcription regulators. As is unsurprising of
      genes, whose products regulate transcription, some of the homeobox-containing
      genes have been associated with malignancy, usually on the basis of abnormal
      structure, or deletions found to occur in tumor cells. The degree of probability
      that these mutated forms were causative in the generation of the tumors in which
      they were found is discussed.

PMID- 1372521
TI  - Regulation of TNF receptors.

PMID- 1372522
TI  - Purification of a multiprotein complex containing centrosomal proteins from the
      Drosophila embryo by chromatography with low-affinity polyclonal antibodies.
AB  - A 190-kDa centrosomal protein interacts with microtubules when Drosophila embryo
      extracts are passed over microtubule-affinity columns. We have obtained a partial
      cDNA clone that encodes this protein. Using a fusion protein produced from the
      clone, we have developed a novel immunoaffinity chromatography procedure that
      allows both the 190-kDa protein and a complex of proteins that associates with it
      to be isolated in in a single step. For this procedure, the fusion protein is
      used as an antigen to prepare rabbit polyclonal antibodies, and those antibodies
      that recognize the 190-kDa protein with low affinity are selectively purified on
      a column containing immobilized antigen. These low-affinity antibodies are then
      used to construct an immunoaffinity column. When Drosophila embryo extracts are
      passed over this column, the 190-kDa protein is quantitatively retained and can
      be eluted in nearly pure form under nondenaturing conditions with 1.5 M MgCl2, pH
      7.6. The immunoaffinity column is washed with 1.0 M KCl just before the elution
      with 1.5 M MgCl2. This wash elutes 10 major proteins, as well as a number of
      minor ones. We present evidence that these KCl-eluted proteins represent
      additional centrosomal components that interact with the 190-kDa protein to form
      a multiprotein complex within the cell.

PMID- 1372523
TI  - Functional expression and growth factor activation of an epitope-tagged p44
      mitogen-activated protein kinase, p44mapk.
AB  - Mitogen-activated protein kinases (MAPKs) or extracellular signal-regulated
      kinases (ERKs) are serine/threonine kinases of apparent Mr 42-44 kDa that are
      rapidly activated by a variety of extracellular signals in many cell types. This
      activation coincides with their phosphorylation on tyrosine and threonine
      residues, and these covalent modifications are required for full activity of the
      enzymes. They are thought to play a pivotal role in integrating and transmitting
      transmembrane signals for growth and differentiation. Here, we report the
      cloning, sequence, and functional expression in fibroblasts of the hamster p44
      MAP kinase (p44mapk). The protein deduced from the nucleotide sequence of an
      almost full-length cDNA is 98.6% homologous to the rat p44mapk (ERK1). To
      distinguish the expression of the cloned cDNA from the endogenous p44mapk, we
      fused to the 5' end of the cDNA an initiating codon followed by an influenza
      hemagglutinin 9-residue peptide epitope (HAP). The chimeric kinase HAP/p44mapk,
      under transcriptional control of the cytomegalovirus promoter, was stably
      expressed in Chinese hamster lung fibroblasts in a functional form. We show that
      its basal activity, measured by phosphorylation of the substrate myelin basic
      protein, is activated severalfold (up to 25) by the mitogens alpha-thrombin,
      platelet-derived growth factor, and fetal calf serum. In addition, we report that
      in response to alpha-thrombin, this activation is rapid (6-fold in 1 min),
      biphasic (first peak at 5 min, second broader peak at 1-2 h), persistent (for
      greater than or equal to 4 h), and parallel to an increased phosphorylation on
      tyrosine.We conclude that the constructed and stably expressed chimera,
      HAP/p44mapk, has retained apparently all the hormonal regulation features of the
      endogenous form. This system now offers the possibility to study structure
      function relationships and to determine the role of this kinase in growth
      control.

PMID- 1372525
TI  - Electrophoretic resolution and fluorescence detection of N-linked glycoprotein
      oligosaccharides after reductive amination with 8-aminonaphthalene-1,3,6
      trisulphonic acid.
AB  - The relative mobilities of various N-linked oligosaccharides reductively aminated
      to the charged fluorophore 8-amino-naphthalene-1,3,6-trisulphonic acid (ANTS)
      were determined by electrophoresis on high-density polyacrylamide slab gels. Each
      ANTS-derivatized oligosaccharide was assigned a relative migration index (RMI)
      expressed in terms of glucose equivalents, which was conveniently estimated by
      reference to a homologous series of ANTS--maltooligosaccharides run on each gel
      as oligosaccharide size standards. High-mannose-, complex- and hybrid-type
      structures were generally well resolved and easily visualized at picomole levels
      by simple UV light excitation. Application of these methods for the qualitative
      analysis of the oligosaccharides released from bovine fetuin and bovine
      asialofetuin by peptide-N-glycosidase F illustrates the usefulness of these
      techniques as fast, simple, and inexpensive tools for the characterization of N
      linked oligosaccharides attached to glycoproteins.

PMID- 1372526
TI  - Epithelioid angiosarcoma of the adrenal gland with cytokeratin expression. Report
      of a case with accompanying mesenteric fibromatosis.
AB  - A case report of epithelioid adrenal angiosarcoma is presented. Tumor cells
      showed expression of cytokeratin, Factor VIII-related antigen, Ulex europaeus
      agglutinin-I, and vimentin. The patient also was found to have mesenteric
      fibromatosis (abdominal desmoid tumor) and an elevated serum level of estradiol.
      The authors discuss the unique appearance of these rare tumors, their
      relationship to hyperestrinism, and review the recent data in the literature
      showing cytokeratin expression by malignant epithelioid vascular tumors.

PMID- 1372524
TI  - c-Kit-kinase induces a cascade of protein tyrosine phosphorylation in normal
      human melanocytes in response to mast cell growth factor and stimulates mitogen
      activated protein kinase but is down-regulated in melanomas.
AB  - The proto-oncogene c-Kit, a transmembrane receptor tyrosine kinase, is an
      important regulator of cell growth whose constitutively active oncogenic
      counterpart, v-kit, induces sarcomas in cats. Mutations in murine c-kit that
      reduce the receptor tyrosine kinase activity cause deficiencies in the migration
      and proliferation of melanoblasts, hematopoietic stem cells, and primordial germ
      cells. We therefore investigated whether c-Kit regulates normal human melanocyte
      proliferation and plays a role in melanomas. We show that normal human
      melanocytes respond to mast cell growth factor (MGF), the Kit-ligand that
      stimulates phosphorylation of tyrosyl residues in c-Kit and induces sequential
      phosphorylation of tyrosyl residues in several other proteins. One of the
      phosphorylated intermediates in the signal transduction pathway was identified as
      an early response kinase (mitogen-activated protein [MAP] kinase).
      Dephosphorylation of a prominent 180-kDa protein suggests that MGF also activates
      a phosphotyrosine phosphatase. In contrast, MGF did not induce proliferation, the
      cascade of protein phosphorylations, or MAP kinase activation in the majority of
      cells cultured from primary nodular and metastatic melanomas that grow
      independently of exogenous factors. In the five out of eight human melanoma lines
      expressing c-kit mRNAs, c-Kit was not constitutively activated. Therefore,
      although c-Kit-kinase is a potent growth regulator of normal human melanocytes,
      its activity is not positively associated with malignant transformation.

PMID- 1372527
TI  - Flow cytometry method for the analysis of membrane-associated human chorionic
      gonadotropin, its subunits, and fragments on human cancer cells.
AB  - A quantitative flow cytometry method for the analysis of membrane-associated
      human chorionic gonadotropin (hCG), its subunits, and fragments on human cancer
      cells was developed using a double-antibody reaction; a flow cytometry with a 2-W
      argon laser, standard settings, and filters for fluorescein isothiocyanate use;
      commercially available software; and the ectopic hCG producer CCL 2 HeLa cells
      from the American Type Culture Collection (ATCC) as a cell control to standardize
      the reagents and for overall quality control. Twenty-two monoclonal antibodies
      (MoAb) and immunoglobulin G fractions from three rabbit polyclonal antisera were
      tested for effects of antibody concentration (titration), reproducibility at
      different levels of epitope expression, and variability of epitope expression to
      select appropriate primary antibodies. Based on the results of the various tests,
      three polyclonal immunoglobulin G antibodies and a panel of nine MoAb directed to
      epitopes located in five different regions on the hCG molecule were selected as
      first antibodies. Their specificity was determined by using two unrelated MoAb of
      the same isotype at the same concentration to replace the primary MoAb and by a
      competition experiment. The unrelated MoAb also were used for the selection of
      the appropriate control fluorescence profile needed for the software. The unique
      characteristics of this method were: the use of living cells, standardized
      reagents, internal and external quality control, and the highest sensitivity,
      which could detect as few as 10(3) molecules of fluorochrome per cell. Serial
      analyses of the ATCC CCL 2 HeLa cells and two of its variants and of the eutopic
      hCG producer JEG-3 choriocarcinoma cells revealed the expression of membrane
      associated epitopes of intact hCG, its subunits, and fragments by a high
      percentage of the cells, indicating that the expression of these
      sialoglycoproteins by these two different types of cancer cells is a common
      phenotypic characteristic.

PMID- 1372528
TI  - Expression of membrane-associated human chorionic gonadotropin, its subunits, and
      fragments by cultured human cancer cells.
AB  - The expression of human chorionic gonadotropin (hCG), its subunits, and fragments
      on the cell membrane of cultured human cancer cells was investigated using a flow
      cytometric method. This method uses living cells; a double-antibody reaction; a
      flow cytometer with an argon laser, standard settings, and filters for
      fluorescein isothiocyanate; commercially available software; the American Type
      Culture Collection (ATCC) CCL 2 HeLa cell line as cell control and overall
      quality control; polyclonal rabbit antisera raised against the hCG dimer, its
      alpha subunit (hCG alpha), and its beta subunit (hCG beta); and a panel of
      monoclonal antibodies (MoAb) recognizing different epitopes on the intact hCG
      molecule, its subunits, and fragments. The purified immunoglobulin G fractions
      from the polyclonal antisera were used to estimate the total expression of the
      membrane-associated glycoproteins; the MoAb were used to detect the expression of
      epitopes of the hCG dimer, its subunits, and fragments. The results of the
      analyses done on cells from 74 established cancer cell lines of different types
      and origins (including 52 carcinomas, 10 sarcomas, 4 leukemias, 6 lymphomas, and
      2 retinoblastomas) showed variable degrees of reactivity in a great percentage of
      cells in all cell lines studied with MoAb directed against different
      conformational epitopes of intact hCG (hCG-holo), hCG beta, hCG beta-free, the
      carboxy terminal peptide (CTP) of hCG beta, and an epitope of hCG alpha. The
      expression of the membrane-associated epitopes of hCG and its subunits was found
      to be a phenotypic marker characteristic of all evaluated cultured human cancer
      cell lines, irrespective of their type or origin. There were, however,
      quantitative and qualitative differences in the expression of the different
      epitopes. Thus, hCG beta, free and as part of hCG-holo, recognized by the MoAb
      against hCG beta-CTP, was expressed by a high percentage of cells of most cell
      lines. There was great variability in the expression of hCG-holo, recognized by
      MoAb B109. For this reason some groups of cancers expressed larger amounts of
      incompetent hCG alpha and/or hCG beta than others. Cell lines derived from
      adenocarcinomas of the lung were the only exception to this general finding; the
      expression of small amounts of hCG-holo was caused by a low degree of hCG alpha
      synthesis.

PMID- 1372529
TI  - Determination of plasma urokinase-type plasminogen activator antigen in patients
      with primary liver cancer: characterization as tumor-associated antigen and
      comparison with alpha-fetoprotein.
AB  - We determined the plasma levels of urokinase-type plasminogen activator (u-PA)
      antigen and alpha-fetoprotein (AFP) in 44 patients with different stages of liver
      cirrhosis and in 29 patients with liver cirrhosis-based primary liver cancer at
      the time of first clinical detection of the malignant disease. Sensitivity values
      of u-PA and AFP in detecting primary liver cancer were 57 and 62%, respectively,
      and specificity values were 95 and 86%, respectively. A combination of both
      markers led to a significant increase of sensitivity to 89.7%. The specificity of
      the combination of both markers was 97.3%. In tumor patients with unilocular
      disease and tumor patients with multicentric disease and/or metastatic spread,
      similar sensitivity values could be obtained with both markers. Therefore, a
      combination of u-PA and AFP can increase the accuracy of detection of primary
      liver cancer, especially in chronic liver diseases known to be predisposing for
      primary liver cancer, e.g., liver cirrhosis of long duration.

PMID- 1372530
TI  - Irradiation-induced expression of O6-methylguanine-DNA methyltransferase in
      mammalian cells.
AB  - O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein which plays
      an important role in chemotherapy, mutagenesis, and carcinogenesis. The specific
      activity of MGMT in female rat liver can be induced by approximately 20-fold by
      treatment of the rats with gamma-irradiation. Maximum response occurred 48 h
      after 15 Gy irradiation. MGMT levels in male rats were induced by only 3-fold.
      MGMT activity was also induced by irradiation of rat hepatoma H4IIE cells with a
      3-fold increase noted after treatment with 3 Gy. Northern analysis and nuclear
      run-on assays indicated that the induction of MGMT was regulated at the
      transcriptional level. The radiation-mediated increase in MGMT was blocked by H7,
      a protein kinase inhibitor, but not by H89, an inhibitor of protein kinase A.
      Hydroxyl radicals may play a role in the induction mechanism since dimethyl
      sulfoxide, a radical scavenger, blocked the radiation-mediated increase in MGMT.
      MGMT activity was also increased by treatment of the cells with H2O2, in
      accordance with the involvement of activated oxygen species in the induction of
      MGMT. Finally, the addition of cycloheximide, an inhibitor of protein synthesis,
      prior to but not after irradiation, abolished the increase in MGMT activity.

PMID- 1372531
TI  - Acquisition of a growth-inhibitory response to phorbol ester involves DNA damage.
AB  - TPA (12-O-tetradecanoylphorbol-13-acetate), a potent tumor promoter, has been
      shown to stimulate or inhibit cell growth depending on the cell type
      investigated. We recently found that RT101 cells, a transformed mouse JB6
      epidermal cell line, acquired a greater growth inhibition response to TPA during
      conventional subcultivation. The growth of low-passage RT101 cells was slightly
      inhibited by TPA in monolayer culture but stimulated in soft agar. In contrast,
      the growth of high-passage cells was greatly inhibited by TPA in both monolayer
      culture and in soft agar. Inhibition was dose dependent, directly correlated with
      protein kinase C-activating activities of tumor promoters, and was found to be
      reversible. TPA-treated high-passage cells were greatly reduced in volume, showed
      extensive abnormal mitoses, and were more susceptible to detachment. High-passage
      cells were also found to be less tumorigenic as indicated by in vivo
      tumorigenicity assay in nude mice. TPA treatment rendered cells still less
      tumorigenic in the case of both cell lines. The mechanism for acquisition of
      increased sensitivity to TPA of RT101 cells during subculture was investigated;
      it involved nonrandom DNA damage and detachment of nonviable cells. The results
      suggest the possibility that early-passage RT101 cells contained two
      subpopulations, one TPA-sensitive and one TPA-resistant population. Conventional
      subcultivation may have selected for the former subpopulation. The sensitive
      subpopulation may have been irreversibly inhibited as a result of TPA-induced
      cell killing, possibly apoptosis.

PMID- 1372532
TI  - Development of mammary preneoplasias in vivo from mouse mammary epithelial cell
      lines in vitro.
AB  - A series of mouse mammary epithelial cell lines has been established by a
      protocol that gives highly reproducible results. The mammary epithelial cell
      lines, designated as FSK lines, were judged to be epithelial based on positive
      immunostaining for keratin-intermediate filaments, negative immunostaining for
      vimentin-intermediate filaments, hormonal induction of casein, and the ability to
      exhibit ductal and alveolar mammary morphogenesis in vivo. The FSK cell lines are
      dependent on epidermal growth factor and insulin in a low serum (1%) medium.
      Conditioned medium from spindle cell cultures replaced the requirement for serum
      and increased the growth of FSK3 and FSK4 4-5 times in collagen gels and 12-14
      times in monolayer culture, respectively. Following injection into the mammary
      fat pad at passages 2-11, the FSK cell lines generated stable transplantable
      hyperplastic alveolar outgrowth lines. The in vivo outgrowth lines were judged as
      preneoplastic based on their stable alveolar morphology in vivo and an increased
      susceptibility for tumorigenesis. The FSK cell lines and their derivative in vivo
      outgrowth lines provide a new and potentially productive system to examine
      critical molecular alterations involved in the development of mammary
      preneoplasias. Furthermore, the reproducibility of the in vitro culture system
      provides the assurance that stable cell lines of mouse mammary epithelial cells
      can be generated easily and at will.

PMID- 1372533
TI  - Tissue-specific expression of a human polymorphic epithelial mucin (MUC1) in
      transgenic mice.
AB  - The human MUC1 gene codes for the core protein of a mucin which is expressed by
      glandular epithelia and the carcinomas which develop from these tissues. The core
      protein is aberrantly glycosylated in cancers, and some antibodies show
      specificity in their reactions with the cancer-associated mucin, which also
      contains epitopes recognized by T-cells from breast and pancreatic cancer
      patients. For evaluating the potential use of mucin-reactive antibodies and mucin
      based immunogens in cancer patients, a mouse model, expressing the MUC1 gene
      product PEM (polymorphic epithelial mucin) as a self antigen, would be extremely
      useful. To this end, we have developed transgenic mouse strains expressing the
      human MUC1 gene product in a tissue-specific manner. The TG4 mouse strain was
      established using a 40-kilobase fragment containing 4.5 kilobases of 5' and 27
      kilobases of 3' flanking sequence. The TG18 strain was developed using a 10.6
      kilobase SacII fragment from the 40-kilobase fragment; this fragment contained
      1.6 kilobases of 5' sequence and 1.9 kilobases of 3' flanking sequence. Both
      strains showed tissue specificity of expression of the MUC1 gene, which was very
      similar to the profile of expression seen in human tissues. The antibody SM-3 is
      directed to a core protein epitope, which is selectively exposed in breast
      cancers and which shows a more restricted distribution on normal human tissues.
      It was established that the distribution of the SM-3 epitope of PEM in the
      tissues of the transgenic mice is similar to that seen in humans. The transgenic
      mouse strains described here should form the basis for the development of a
      preclinical model for the evaluation of PEM-based antigens and of antibodies
      directed to PEM in cancer therapy.

PMID- 1372534
TI  - Phenylacetate: a novel nontoxic inducer of tumor cell differentiation.
AB  - Sodium phenylacetate was found to affect the growth and differentiation of tumor
      cells in vitro at concentrations that have been achieved in humans with no
      significant adverse effects. Treatment of promyelocytic leukemia HL-60 cells
      resulted in the rapid decline of myc oncogene expression followed by growth
      arrest and granulocyte differentiation. Phenylacetate also induced highly
      efficient adipocyte conversion in immortalized mesenchymal C3H 10T1/2 cultures;
      yet, unlike the differentiating chemotherapeutic drug 5-aza-2'-deoxycytidine,
      phenylacetate did not cause neoplastic transformation in these susceptible cells.
      The results indicate that phenylacetate is both effective in inducing tumor cell
      maturation and free of cytotoxic and carcinogenic effects, a combination that
      warrants attention to its potential use in cancer intervention.

PMID- 1372536
TI  - Loss of microvascular negative charges accompanied by interstitial edema in
      septic rats' heart.
AB  - We studied the effect of Gram-negative sepsis on negative charges of heart
      capillaries and myocardial cells. We used a rat model of multiorgan failure, with
      ruthenium red (RR) and polyethyleneimine (PEI) as cationic binding tracers.
      Twenty-four hours after induction of sepsis, negative charges had decreased in
      glycocalyx and basement membrane of myocardial capillary endothelial cells. There
      were substantial amounts of interstitial edema. Density of anionic charges in the
      sarcolemmal glycocalyx complex of cardiac cells was markedly reduced. Myocardial
      cells' mitochondria consistently showed morphologic changes, whose severity
      ranged between stages II and IV C of Trump. Thirteen days after induction of
      sepsis, capillary endothelial and myocardial cells had recovered almost
      completely and showed no intracellular edema. Gram-negative sepsis caused a
      significant reduction in negative charges normally present in the microvascular
      wall as well as on myocardial cells. Consequently, several membranes limiting the
      various compartments of heart tissue lost their structural integrity. This
      morphometric data could explain the development of protein-rich interstitial
      edema and defective cell volume regulation observed in cardiac muscle of
      endotoxin-shocked animals. This myocardial edema may be at the origin of the
      cardiac dysfunction observed in both experimental and human septic shock.

PMID- 1372535
TI  - Expression of fibroblast growth factor receptors in human leukemia cells.
AB  - We have previously cloned from K562 leukemia cells two novel fibroblast growth
      factor receptors (FGFR-3 and FGFR-4; J. Partanen et al., EMBO J., 10: 1347-1354,
      1991). Here we have analyzed the mRNA expression of four different FGFRs,
      including the two novel genes in human leukemia cell lines. We show FGFR-1, FGFR
      3, and FGFR-4 mRNAs in several leukemia cell lines at levels similar to those in
      solid tumor cell lines. Ligand cross-linking experiments indicate that K562 cells
      have receptors binding acidic FGF but not basic FGF. Expression of FGFRs in
      leukemia cells may reflect their presence on normal hematopoietic precursor cells
      or induction during leukemogenesis or cell culture.

PMID- 1372537
TI  - Activation of chloride current by purinergic stimulation in guinea pig heart
      cells.
AB  - Single atrial cells from guinea pig heart were voltage-clamped using the whole
      cell configuration of the patch-clamp technique under conditions in which most of
      the ionic and exchange currents known in cardiac cells were minimized.
      Extracellular 5 or 50 microM ATP activated a Cl- current, in addition to a
      rapidly desensitizing cation-selective current. A nonhydrolyzable ATP analogue,
      adenosine-5'-O-(3-thiotriphosphate) (50 microM), also evoked these two currents,
      indicating involvement of purinoceptors rather than ecto-ATPase on the membrane.
      ADP, AMP, and adenosine were also effective in inducing the Cl- current, showing
      no clear order of potency for the purinoceptor subtypes involved. The
      purinoceptor-activated Cl- current, like the beta-catecholamine-cAMP-dependent
      cardiac Cl- current, showed outward rectification and time independence.

PMID- 1372538
TI  - Experimental therapies for multiple sclerosis: current status.
AB  - Multiple sclerosis is the most common cause of nontraumatic disability affecting
      young adults in the United States. Its etiology remains unclear, but evidence
      points to alteration of normal immune system function in the pathogenesis of this
      illness. This article reviews the results of clinical trials of experimental
      therapeutic agents in multiple sclerosis. The background and action of each
      treatment are described, and the clinical experience with each agent is reviewed.
      Obstacles to evaluating the effectiveness of treatment methods in MS and
      challenges to the design of future clinical trials and the interpretation of
      trial outcomes are discussed.

PMID- 1372540
TI  - Spatial expression of genes encoding c-kit receptors and their ligands in mouse
      cerebellum as revealed by in situ hybridization.
AB  - Expression of mRNA for c-kit receptors and their ligands was examined in the
      cerebellum of mice by in situ hybridization technique. The c-kit receptors were
      expressed in the molecular layer of the cerebellum and the ligands for the c-kit
      receptors were detected at the boundary of molecular and granular layers. The
      expression of the c-kit ligands was not detectable in the cerebellum of lurcher
      (Lc/+) mutant mice that lack Purkinje cells, indicating the cells expressing the
      c-kit ligands were Purkinje cells. The cells expressing c-kit receptors decreased
      but were present in the cerebellum of Lc/+ mice. The c-kit mRNA-positive cells
      appeared to represent basket cells and stellate cells from their appearance and
      location. Since neurons in the molecular layer construct suppressive
      neurojunctions with Purkinje cells, the present result suggests that c-kit
      receptors and their ligands may play an important role for the construction of
      their junctions.

PMID- 1372539
TI  - Postnatal development of electrogenic sodium pump activity in rat hippocampal
      pyramidal neurons.
AB  - We assessed the development of electrogenic sodium pump (Na+ pump) activity in
      CA1 pyramidal neurons of rat hippocampal slices by studying the prolonged
      hyperpolarization which follows glutamate-induced depolarization (postglutamate
      hyperpolarization or PGH) at different postnatal ages. We also examined the
      development of membrane-bound enzyme in the hippocampal CA1 subfield with light
      microscopic immunocytochemistry and an antiserum against Na+,K(+)-ATPase. The
      PGH, which has previously been shown to be due to activation of an electrogenic
      Na+ pump in adult hippocampal CA1 neurons, was eliminated by strophanthidin, a
      Na+,K(+)-ATPase inhibitor, at all ages. It was unaffected by several potassium
      channel blockers, an intracellular calcium chelator, intracellular Cl- injection
      or tetrodotoxin (TTX) perfusion. The PGH thus appeared to be independent of K+
      and Cl- conductances and produced by an electrogenic Na+ pump in adult and
      immature animals activated in large part by entry of Na+ through the glutamate
      receptor-channel complex. The size (integrated area) of the PGH was directly
      proportional to the area of preceding glutamate-induced depolarization (GD) and
      relatively voltage independent. Similar GDs could be elicited from postnatal day
      (P) 7 to P greater than or equal to 35, however, only very small PGHs were
      produced in neurons from P7-11 animals. A ratio of PGH area to GD area (PGH
      ratio) was calculated for each neuron and used to compare Na+ pump activity at
      different ages. There was a significant increase in the mean PGH ratio with age
      when P7-11, P21-25 and P35-39 groups were compared. Na+ pump activity estimated
      from the PGH ratio is very low in the first postnatal week but develops gradually
      over the first 5 weeks of life. Immunostaining for Na+,K(+)-ATPase in adult rat
      hippocampi revealed a punctate reaction product surrounding pyramidal cell
      bodies, whereas the staining was uniform along plasmalemma of dendrites in
      stratum radiatum and stratum oriens. By contrast, only minimum staining was
      present surrounding cell bodies and dendrites of P7 hippocampi and staining in
      stratum pyramidale was not punctate at this age. Na+,K(+)-ATPase activity
      estimated grossly from immunocytochemical staining is very low in the first
      postnatal week, increases during the first 5 weeks and develops a characteristic
      focal localization.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1372541
TI  - Ontogeny of glycine-enhanced [3H]MK-801 binding to N-methyl-D-aspartate receptor
      coupled ion channels.
AB  - The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor is thought to play
      a critical role in neuronal development, differentiation and plasticity. A number
      of studies have shown an enhanced sensitivity to NMDA receptor ligands in
      neonatal animals. This study examined the ontogenetic changes in the glycinergic
      modulation of NMDA-coupled cation channels in the developing central nervous
      system of rat pups. The nonequilibrium binding of the specific channel ligand
      [3H]MK-801 was used as a measure of NMDA channel access. Glycine (10(-5) M)
      enhancement of [3H]MK-801 binding at 2 h in forebrain membranes from adult rats
      was significantly greater than that observed in tissues from 8- to 28-day-old rat
      pups. This difference was due to changes in the efficacy, but not potency of
      glycine. The observed ontogenetic changes in the efficacy of glycine-enhanced
      [3H]MK-801 binding were attributable to developmental changes in receptor site
      density, as determined by equilibrium [3H]MK-801 saturation isotherms. Kinetic
      studies revealed that glycine increased the association rate constants of [3H]MK
      801 in 8-day and adult membranes by a similar magnitude (0.111 +/- 0.021 vs 0.094
      +/- 0.009 nM-1 h-1, respectively). Similarly, the fractional amount of [3H]MK-801
      bound (i.e., amount bound at time t normalized to amount bound at equilibrium) in
      the presence of glycine was relatively constant throughout neonatal development.
      These findings suggest that the allosteric modulation of the NMDA ionophore by
      glycine is similar in postnatal and adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372542
TI  - Alport-type glomerulopathy: evidence for diminished capillary loop size.
AB  - Hereditary nephropathy of the Alport type is morphologically characterized by a
      specific and diagnostic thinning and splitting lesion of the glomerular basement
      membranes, which can be recognized only by electron microscopy. The light
      microscopical aspect has not been considered to be characteristic until now. This
      paper describes a light microscopical constellation of glomerular alterations by
      which ATGP can be recognized with high probability. Three histological features
      are of importance: 1. ATGP glomeruli in patients older than 10 years of age
      mostly have smaller capillary loops than age-matched controls. However, during
      the first 10 years of life no difference in glomerular capillary loop size was
      noticed. 2. ATGP loops often stain less intensely with basement membrane stains.
      3. Presence of fetal-like glomeruli. Using this triad of light microscopic
      parameters as a screening tool, ATGP-cases were found without knowledge of any
      clinical data among other glomerulopathies with a sensitivity of 72% and a
      specificity of 93%. The definitive diagnosis, however, depends on electron
      microscopy.

PMID- 1372544
TI  - Chlamydial rRNA in the joints of patients with Chlamydia-induced arthritis and
      undifferentiated arthritis.
AB  - Synovial fluid and synovial membrane specimens of 11 patients with Chlamydia
      induced arthritis (CIA), 24 patients with undifferentiated arthritis (UndA), 4
      patients with post-enteritic reactive arthritis, 3 patients with Lyme arthritis
      and 9 patients with rheumatoid arthritis were investigated for the presence of
      Chlamydia trachomatis (C. trachomatis). A single stranded DNA-probe was used for
      nucleic acid hybridization with ribosomal RNA (rRNA) from C. trachomatis. In 4
      patients (CIA = 1, UndA = 3) chlamydial rRNA was found in the synovial fluid. In
      one additional patient (CIA) the specimen of a synovial membrane biopsy was
      positive for chlamydial rRNA. The detection of intra-articular chlamydial rRNA is
      discussed as an indicator for the presence of viable Chlamydiae in inflamed
      joints.

PMID- 1372543
TI  - Antibodies against terminal galactosyl (alpha 1-3) galactose epitopes in systemic
      sclerosis (scleroderma).
AB  - Sera from 224 patients with systemic sclerosis (scleroderma) were analyzed for
      circulating antibodies against an antigenic determinant characterized by two
      molecules of galactose in alpha 1-3 linkage. About 45% of the patients were found
      to have values above the normal range. The mean antibody level was significantly
      higher than that found in normal subjects (p less than 0.001) or in patients with
      primary Raynaud's phenomenon who were included as controls. The mean level of
      anti-Gal antibodies correlated with the degree of skin and internal organ
      involvement, as well as with the presence of progression or inflammation.
      Furthermore, when patients with early onset disease were analyzed, high levels of
      anti-Gal antibodies were present in the subgroups characterized by evidence of
      progression or inflammation, whereas patients with stable disease did not differ
      from the controls. We conclude that humoral immunity against Gal alpha 1-3 Gal is
      an early feature of scleroderma, may be important for its pathogenesis, and may
      provide a more sensitive tool to detect disease activity.

PMID- 1372545
TI  - Design principles for computerized EEG monitoring.

PMID- 1372546
TI  - Epileptiform activity in chronically isolated cerebral cortex in humans.
AB  - The ability of neuronally isolated human cerebral cortex to sustain epileptiform
      rhythms over long time intervals is unknown. We report here two patients after
      functional hemispherectomy for infantile hemiplegia and infantile
      meningoencephalitis. Both patients had intractable seizures. EEG performed early
      and up to 3 years after surgery showed persistent epileptiform activity in the
      isolated frontal cortex in both cases. This indicates that human isolated cortex
      retains its epileptogenic potential for years, independently of subcortical
      influences. Previous related animal and human studies are briefly reviewed.

PMID- 1372547
TI  - Detection and evolution of rhythmic components in ictal EEG using short segment
      spectra and discriminant analysis.
AB  - An automated method for analysis of ictal EEG is described which aims to reliably
      detect one or several rhythmic components in short EEG segments (2 sec) and to
      display their presence, frequency, amplitude, location, and temporal evolution.
      Spectra were estimated and compared using fast Fourier transform (FFT) and
      autoregressive modelling (AR). A subsequent linear discriminant analysis decided
      whether a spectral peak is likely to be caused by rhythmic activity or by the
      inherent statistical variability. FFT was found to perform better than AR in the
      detection of rhythmic components, yielding a false-positive rate of 0.825%, a
      false-negative rate of 2% (signal to noise ratio -4.6 dB), a frequency resolution
      of 2 Hz, and a temporal resolution of 0.5 sec. Seizure analysis revealed that the
      ictal scalp EEG of even short seizures can show a complex evolution of rhythmic
      patterns which are impossible or difficult to recognize by visual inspection or
      conventional spectral analysis. The following phenomena are demonstrated:
      superposition of two rhythmic components suggesting two cerebral regions
      discharging simultaneously and independently with their own pacemakers, sudden
      and gradual change of frequencies, and gradual development of harmonic
      frequencies. It is suggested that a more precise correlation between rhythmic
      generators and seizure symptomatology might allow more predictable
      pharmacological responses in antiepileptic therapy.

PMID- 1372548
TI  - Changes in cortical activity when subjects scan memory for tones.
AB  - The magnetoencephalogram (MEG) was used to detect regional changes in spontaneous
      cortical activity accompanying short-term memory search. This method was chosen
      because magnetic fields are detectable only within a few centimeters of the
      projections of their sources onto the scalp. The specific hypothesis that
      auditory cortex is involved in scanning memory for tones was tested by sensing
      the field of the magnetic counterpart to N100 (N100m) which is known to originate
      in auditory cortex. N100m was measured at many different positions and the
      spontaneous cortical rhythms in the alpha bandwidth (8-12 Hz) were measured at
      the same places. These rhythms were found to be suppressed while subjects scanned
      memory for musical tones in a Sternberg paradigm. For 3 subjects, both the MEG
      suppression time (ST) and reaction time (RT) increased linearly with memory set
      size. The correlation between ST measured over the left hemisphere and set size
      was significant for two subjects but not significant for the third, and the
      slopes of the regression lines relating ST to set size were too shallow to be
      related to the time required to scan memory. However, the correlation between ST
      of the right hemisphere and set size was highly significant for all subjects, and
      the slopes of the regression lines were comparable to those relating RT to set
      size. The electroencephalogram (EEG) recorded with midline electrodes failed to
      reveal a significant relationship between suppression time and set size for 2 of
      the subjects, thus ruling out global alpha blockage and generalized arousal as
      the basis for the task-related suppression duration. The electric N100, measured
      at Cz, decreased significantly in amplitude with set size for 2 subjects, but it
      increased significantly in amplitude for the third subject. In contrast, RT
      increased with set size for all subjects. N100m measured over the right
      hemisphere was similar to the behavior of N100, while N100m measured over the
      left hemisphere showed little change in amplitude with set size, thus
      establishing an asymmetry in N100 between the hemispheres. Since N100 amplitude
      is normally larger when attention is paid to auditory stimuli, differential
      attention alone cannot account for the relation between ST and set size.
      Furthermore, the processing negativity, which may be superimposed on N100 in
      selective attention tasks, was not discernible for any set size. It was also
      found that ST prior to the button press was not correlated with RT. Hence, the
      covariation of set size with ST is not attributable to preparation for a motor
      response.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1372549
TI  - Cortical DC potential shifts accompanying auditory and visual short-term memory.
AB  - Negative DC potential shifts appeared over the scalp during the performance of
      verbal and non-verbal short-term memory tasks. Three items were successively
      presented (presentation of memory items) and then had to be retained in memory
      for 3 sec (memory retention) before being compared to a probe which was either a
      member (in set) or not a member (out of set) of the memory set. Verbal items (the
      digits "1" through "9") were tested in the auditory and visual modality and non
      verbal items (musical notes) were tested in the auditory modality. Stimulus
      modality had a significant effect on DC potential shifts during both presentation
      of memory items and memory retention. There was a sustained negative shift during
      these periods which was larger over frontal regions with auditory than with
      visual material whereas the negative shift was larger over posterior temporal
      regions with visual than with auditory material. Out of 21 subjects who
      participated in the study, 9 reported the use of visual images in the auditory
      task, 5 used subvocal auditory rehearsal in the visual task and 7 used imagery
      concordant with the stimulus modality being memorized. These different strategies
      had a significant effect on the amplitudes and distribution of the DC potential
      shifts. The speed of response affected the amplitude of the DC potential shifts
      in the frontal regions, being larger with fast RTs than with slow RTs but only
      when verbal items were being processed. These results indicate that stimulus
      modality, modality of mental imagery, and speed of scanning of the memory store
      affect DC potential shifts during a 3 sec period of memory retention.

PMID- 1372550
TI  - Properties of neuronal activity in cortex and subcortical nuclei of the human
      brain during single-word processing.
AB  - Neuronal impulse activity (NIA) in different cortical areas, subcortical nuclei
      of the thalamus and striopallidum was recorded via depth electrodes in human
      patients as they performed a visual word recognition task. The properties of
      neuronal responsiveness were compared across regions. During single-word
      processing approximately 75-80% of the responsive cortical neurons were
      characterized by poststimulus inhibition of firing rate; an increased firing rate
      (i.e., excitatory response) was observed in about 20-25% of the responsive
      cortical neurons. Among the subcortical nuclei, mainly in the thalamus and
      striopallidum, more than 90% of the responsive neurons were characterized by
      poststimulus excitation; less than 10% exhibited poststimulus inhibition of
      firing rate.

PMID- 1372551
TI  - Event-related desynchronization: the effects of energetic and computational
      demands.
AB  - The effects of a subject's activation state on cognitive processing were studied,
      while subjects performed verbal and non-verbal tasks under a speed and accuracy
      instruction. It was found that stressing speed influenced the level of
      prestimulus alpha power and consequently the amount of relative event-related
      desynchronization (ERD). Increasing task complexity led to an increase in the
      amount and duration of relative ERD. Both prestimulus level of alpha power and
      relative ERD were asymmetrically distributed over the left and right hemispheres.
      No verbal/non-verbal task-dependent asymmetries in phasic ERD were found. The
      data suggest that the level of prestimulus alpha power is mainly influenced by
      the subject's activation state, whereas relative ERD mainly reflects phasic
      changes in cognitive processing.

PMID- 1372552
TI  - Unilateral 14 and 6 Hz positive bursts.
AB  - We describe the unilateral occurrence of 14 and 6 Hz positive bursts in
      successive EEGs in a 25-year-old woman following surgical resection of a left
      parietal arteriovenous malformation which had caused a left parieto-temporal
      intracerebral hematoma. This is only the second reported case of unilateral 14
      and 6 Hz positive bursts. This could represent either a normal pattern seen
      unilaterally because of a skull defect or be a manifestation of neuronal damage.

PMID- 1372553
TI  - Prediction of the side of hand movements from single-trial multi-channel EEG data
      using neural networks.
AB  - Thirty channels of EEG data were recorded prior to voluntary right or left hand
      movements. Event-related desynchronization (ERD) was quantified in the 8-10 Hz
      and 10-12 Hz bands in single-trial data and used as training input for a neural
      network comprised of a learning vector quantizer (LVQ). After a training period,
      the network was able to predict the side of hand movement from single-trial EEG
      data recorded prior to movement onset.

PMID- 1372554
TI  - Selective effect of poly(lysine) on the enhancement of the lyn tyrosine protein
      kinase activity. Increased specificity toward src peptides.
AB  - A tyrosine protein kinase (TPK-I), isolated from rat spleen [Brunati, A. M. &
      Pinna, L. A. (1988) Eur. J. Biochem. 172, 451-457] and recently identified as the
      product of the lyn oncogene [Brunati, A. M., Donella-Deana, A., Ralph, S.,
      Marchiori, F., Borin, G., Fischer, S. & Pinna, L. A. (1991) Biochim. Biophys.
      Acta 1901, 123-126], is stimulated by a variety of effectors, including
      poly(lysine), heparin and very high NaCl concentrations. The efficacy of these
      compounds is variably dependent on the nature of the phosphoacceptor peptide
      substrates. Here we show that poly(lysine), but neither NaCl nor heparin,
      specifically enhances the phosphorylation efficiency of lyn TPK for the peptide
      EDNEYTA (src peptide). It reproduces the main autophosphorylation site of pp60c
      src (Tyr416), which is entirely conserved in lyn TPK. The favourable effect of
      poly(lysine) is accounted for by both a dramatic drop of the Km value (70 microM
      versus 670 microM) and more than a threefold increase in Vmax. The effect is not
      so evident with a variety of different peptides, either unrelated to the src
      peptide (e.g. angiotensin II, AAYAA) or derived from the src peptide by single or
      multiple substitutions of the residues located on the N-terminal side of
      tyrosine. In particular, the responsiveness to poly(lysine) is dramatically
      reduced whenever alanine is replaced for either asparagine at position -2 or
      glutamic acid at position -1, either in the src heptapeptide or in its shorter
      derivative, the pentapeptide NEYTA. In sharp contrast, the favourable effect of 2
      M NaCl, which is invariably accounted for only by an increased Vmax, is
      especially evident with peptides like angiotensin II and AAYAA, whose
      phosphorylation is less sensitive to poly(lysine) stimulation. The
      phosphorylation of the src peptides are actually inhibited rather than stimulated
      by 2 M NaCl. Consistent with this, lyn TPK autophosphorylation is also
      dramatically stimulated by poly(lysine) while being inhibited by 2 M NaCl. These
      data show that poly(lysine) deeply alters the selectivity of lyn TPK by
      conferring to it an enhanced activity and an especially high affinity toward
      peptides that reproduce the conserved autophosphorylation site of the TPK of the
      src family. It is suggested that endogenous compound, whose effect is mimicked by
      poly(lysine) in vitro, may play a relevant role in determining the specificity of
      lyn TPK in vivo and possibly of other TPK of the src family.

PMID- 1372555
TI  - Tissue distribution and change in potato starch phosphorylase mRNA levels in
      wounded tissue and sprouting tubers.
AB  - Starch phosphorylase has been cloned from a lambda gt10 cDNA library of potato
      tuber mRNA. Selected recombinants have been used to demonstrate that
      phosphorylase mRNA is most abundant in tubers but is also detectable in stolon,
      root, stem and leaf tissue. The level of phosphorylase mRNA was greatly reduced
      in wounded stem and tuber tissue. The wounding-induced decrease in phosphorylase
      mRNA levels is not reversed in the presence of sucrose or mannitol. Regional
      differences are described in the levels of phosphorylase and patatin mRNA in
      different parts of the tuber and in the shoot of sprouting potatoes.

PMID- 1372556
TI  - Interleukin-7 expression during mouse thymus development.
AB  - We have monitored the expression of interleukin-7 (IL-7) in the developing
      embryonic mouse thymus by a combination of quantitative polymerase chain reaction
      (PCR) and immunofluorescence microscopy. A strong specific signal for IL-7 mRNA
      was detected by day 12 in the developing fetal thymus. IL-7 mRNA was found to be
      maximally expressed on day 15, and then decreased over the next 5 days.
      Immunofluorescence staining of fetal thymus sections using an anti-IL-7 antibody
      confirmed these PCR data. IL-7 protein expression was first detected at day 13 of
      development. At 14 days the intensity of the staining increased by a factor of
      three and stayed at this level over the next 4 days. The same anti-IL-7 antibody
      used for immunofluorescence, blocked the proliferation of fetal thymocytes in
      organotypic cultures. In addition, we detected mRNA coding for IL-2 and SCF (also
      known as the steel factor or KL) in embryonic thymocytes. The implications of
      these findings for early thymocyte growth are discussed.

PMID- 1372557
TI  - Antibody binding to a collagen type-II epitope gives rise to an inhibitory
      peptide for autoreactive T cells.
AB  - It is well documented that antigen recognition by T cells requires small peptides
      which are generated by protein cleavage in antigen-presenting cells. These
      peptides have to associate with major histocompatibility complex (MHC) molecules
      in order to be recognized. An inhibitory peptide may bind to the same site of the
      MHC-encoded protein but is not recognized by the T cell. Here we describe a
      stimulatory and an inhibitory peptide sequence within human collagen type II
      (CII) as defined by means of the same autoreactive human T cell clone. Most
      interestingly, the inhibitory peptide is not generated by regular processing in
      peripheral blood mononuclear cells but only in the presence of an antibody that
      binds to the same domain and thereby seems to protect the inhibitory sequence.
      This finding may indicate that certain autoantibodies have the potential to block
      autoreactive T cells with specificity for a distinct epitope on the same antigen.

PMID- 1372558
TI  - Increased numbers of T cells recognizing multiple myelin basic protein epitopes
      in multiple sclerosis.
AB  - Myelin basic protein (MBP)-autoreactive T cells have a crucial pathogenetic role
      in experimental allergic encephalomyelitis (EAE) and certain MBP epitopes may be
      immunodominantly recognized. The heterogeneity and quantity of the T cell
      response to different epitopes of MBP in multiple sclerosis (MS) and non-MS
      controls is not so clearly defined. We now study T cell reactivity to six
      different peptides of MBP in MS compared to controls in short-term cultures of
      blood mononuclear cells by measuring numbers of T cells that secrete interferon
      gamma in response to antigen. In comparison with controls, MS patients showed
      dramatically increased numbers of MBP peptide-reactive T cells with mean values
      varying between 10.4 and 22.5 per 10(5) blood mononuclear cells. Among those MBP
      peptides examined (amino acid 1-20, 63-88, 89-101, 96-118, 110-128 and 148-165),
      no single peptide is preferentially recognized. Neither is any preferential
      response apparent after subdivision of the MS patients according to their HLA-DR
      genotype. Our findings suggest that a quantitative increase of a broad repertoire
      of myelin-autoreactive T cells with capacity to secrete IFN-gamma can be
      important for the pathogenesis of MS.

PMID- 1372559
TI  - Tissue-specific migration pathways by phenotypically distinct subpopulations of
      memory T cells.
AB  - A proportion of T cells recirculate in a tissue-selective manner. Recent studies
      which showed that the skin-tropic subset of T cells was of memory/activated type,
      led us to examine whether the preferential homing of T cells to the gut also
      involved memory T cells, and if so whether these memory T cells were
      phenotypically distinct from other memory T cells. Lymphocytes migrating through
      the gut and the skin of sheep was collected by cannulating the lymphatic ducts
      draining these tissues. Both naive and memory T cells were found to recirculate
      through the gut, although only memory T cells migrated through the skin. However,
      when T cells from the gut were labeled with fluorescein isothiocyanate and
      assessed for their migration back to the gut, it was the memory population which
      showed a tropism for the gut. Gut-tropic memory T cells migrated poorly through
      the skin, indicating that these cells were distinct from skin-tropic memory T
      cells. This was confirmed by phenotypic analysis. Gut memory T cells expressed
      very low levels of the alpha 6 and beta 1 integrins, in contrast to skin memory T
      cells which expressed high levels. There was no evidence for heterogeneity within
      the naive T cell population, which migrated preferentially to lymph nodes. This
      migration pattern could be explained in part by the high expression of the L
      selectin (lymph node homing receptor, LAM-1) on naive T cells, in contrast to
      memory T cells from gut or skin which were mostly L-selectin negative. These
      results in sheep indicate that subsets of alpha/beta memory T cells show tissue
      selective migration patterns, which probably develop in a particular environment
      following encounter with antigen.

PMID- 1372560
TI  - Identification of the nonamer peptide from influenza A matrix protein and the
      role of pockets of HLA-A2 in its recognition by cytotoxic T lymphocytes.
AB  - Influenza matrix peptide 58-66 is shown to be the optimal nonamer for binding to
      HLA-A2 and presentation to cytotoxic T lymphocytes (CTL). If titered out to 2 x
      10(-10) - 4 x 10(-10) M in CTL-mediated lysis assays and to 3 x 10(-9) M in an
      HLA-A2 assembly-stabilization assay in cell lysates. The peptide was shown to
      make probable contacts with its carboxy terminus close to residue 116 in the
      floor of the cleft of HLA-A2, close to the F pocket. The side chain of the amino
      terminal amino acid was unimportant, but its free amino and carbonyl groups in
      the A pocket appeared important in optimizing peptide presentation. The B pocket
      probably accommodates the side chain of residue 2 (isoleucine) and was shown to
      be critical in peptide presentation.

PMID- 1372561
TI  - T cell epitope selection: dominance may be determined by both affinity for major
      histocompatibility complex and stoichiometry of epitope.
AB  - The majority of T cell hybridomas produced in the BALB/c mouse in response to
      immunization with lambda repressor cI recognize a peptide fragment comprising of
      residues 12 to 26 (P12-26). Some other parts of the cI (P1-14, P33-48 and P73-88)
      are defective in generating T cell responses in the BALB/c mouse. P73-88 may be
      converted into a T cell determinant if a few more amino acid residues are
      included (P67-88). Together with P46-67 and P80-102, most peptides derived from
      cI were capable of eliciting T cell responses by themselves in BALB/c mouse. The
      mechanisms underlying the selection of P12-26 over the other epitopes when lambda
      repressor was used as immunogen were examined. The dominant response to P12-26
      was attenuated by tolerizing with intravenous administration of P12-26. Under
      such treatment the T cell response to P12-26 was reduced by 80% but there was no
      enhancement on the responses toward other epitopes. The selection of P12-26 is,
      thus, unlikely to be due to a competition at the T cell level. It was also found
      that the dominance of P12-26 was not simply due to a higher affinity of P12-26
      for major histocompatibility complex molecules. For example P12-26 binds better
      to I-Ad molecule than P80-102, but co-injection with equimole of P12-26 only
      slightly inhibited P80-102-induced T cell response. Instead, it required a few
      molar excess of P12-26 to effectively block the association of P80-102 with I-Ad
      molecules and to inhibit the T cell immunity to P80-102. Since epitopes such as
      P46-67, P67-88 and P80-102 were generated from lambda repressor cI at a lower
      molar basis than that of P12-26, it is suggested that the dominance of P12-26 was
      probably generated by such stoichiometry difference, in addition to the higher
      affinity of P12-26 for I-Ad molecules.

PMID- 1372562
TI  - Interferon-gamma regulates expression of a novel keratin class I gene.
AB  - Interferon (IFN)-gamma has been implicated in the pathogenesis of several
      autoimmune disorders and inflammatory skin diseases. To identify novel mediators
      involved in the IFN-gamma response we have used differential hybridization of a
      cDNA library prepared from IFN-gamma-treated HeLa cells to isolate a gene that is
      induced following treatment with IFN-gamma. We report here the molecular cloning
      and characterization of a cDNA detecting a 1.6-kb mRNA that accumulated in
      response to IFN-gamma but not in response to IFN-alpha or IFN-beta. The gene is
      regulated by IFN-gamma in human cell lines of epithelial origin. The mRNA encodes
      a predicted protein of 432 amino acids and the primary structure of the protein
      demonstrates that it is a novel member of developmentally regulated keratin class
      I genes.

PMID- 1372563
TI  - Induced RAW 264.7 macrophages express soluble and particulate nitric oxide
      synthase: inhibition by transforming growth factor-beta.
AB  - RAW 264.7 macrophages induced with lipopolysaccharide and interferon-gamma
      expressed nitric oxide (NO) synthase. Approximately two-thirds of the total
      induced NO synthase activity was found in the cytosolic fraction, whereas one
      third was associated with the particulate fraction. Both enzymes formed L
      citrulline in addition to NO-like material. NO and L-citrulline formation by both
      enzymes were calcium-independent and inhibited by NG-nitro-L-arginine and NG
      methyl-L-arginine. Transforming growth factor-beta 1 prevented the induction of
      both enzymes.

PMID- 1372564
TI  - Expression analysis of ruminant alpha-lactalbumin in transgenic mice:
      developmental regulation and general location of important cis-regulatory
      elements.
AB  - The bovine alpha-lactalbumin transgene with 750 bp and 336 bp of the 5' and 3'
      flanking region, respectively, is developmentally regulated as its endogenous
      counterpart in transgenic mice. Comparative expression analysis of three 5'
      shortened constructs suggests that the region -477/-220 contains important cis
      acting transcriptional elements. The level of expression of a long caprine alpha
      lactalbumin transgene encompassing 8.5 kb and 9.5 kb of the 5' and 3' flanking
      region, respectively, was higher but still unrelated to the copy number.
      Expression of the transgenes and of endogenous milk-protein genes was tissue
      specific. In contrast with a recent report, only low amounts of the relevant mRNA
      were detected in some skin samples, which suggests a possible contamination by
      mammary tissue.

PMID- 1372565
TI  - Induction of nitric oxide synthase by lipoteichoic acid from Staphylococcus
      aureus in vascular smooth muscle cells.
AB  - Inducible vascular nitric oxide synthase accounts for the contractile impairment
      observed in endotoxemia. We provide evidence that lipoteichoic acid (LTA) from
      Staphylococcus aureus, a micro-organism without endotoxin, also induces nitric
      oxide synthase. Our study demonstrates that on endothelium-free rings of rat
      aorta. LTA-like lipopolysaccharide induces a loss of contractility restored by
      Methylene blue and NG-nitro-L-arginine-methyl ester (LNAME). Moreover in cultured
      vascular smooth muscle cells, LTA produces a dose-dependent increase in
      intracellular cyclic GMP which is antagonized by LNAME and prevented by
      dexamethasone.

PMID- 1372566
TI  - Effect of ploidy on transcription levels in cultured rat aortic smooth muscle
      cells.
AB  - Aging and hypertension increase the number of polyploid smooth muscle cells (SMC)
      in a blood vessel. We assessed the effect of ploidy on the transcription of
      several genes in SMC cultures derived from newborn and adult rats. In diploid and
      tetraploid subcultures of SMC from newborn rats, RNA expression of the genes
      assayed is linked with ploidy. However, when phenotypically different SMC
      cultures derived from newborn and adult rats were compared, transcription levels
      varied from gene to gene and not linked with the ploidy. Thus, differences in
      gene expression due to polyploidy are superimposed on those due to other
      phenotypical features.

PMID- 1372567
TI  - A novel 15N-labeling method to selectively observe 15NH2 resonances of proteins
      in 1H-detected heteronuclear correlation spectroscopy.
AB  - An experimental method to selectively label side-chain NH2 groups of glutamine
      and asparagine in proteins with 15N is proposed. This selective labeling method
      enables to observe only 15NH2 resonances and thus, to discriminate between 15NH
      and 15NH2 resonances in a 1H-detected heteronuclear correlation spectrum. This
      method gives results with approximately two times higher sensitivity than those
      obtained by elaborate pulse sequences such as DEPT-HSQC and will be useful for
      studying the molecular interaction involving the side chains of Asn and Gln
      residues.

PMID- 1372568
TI  - Alternative promotion of aromatase P-450 expression in the human placenta.
AB  - We have previously reported the isolation and characterization of the human gene
      encoding aromatase cytochrome P-450 (P-450AROM). The gene had been demonstrated
      to span at least 52 kb and contain ten exons, the first of which, exon I.1, is
      untranslated. Here we report the isolation and characterization of a P-450AROM
      cDNA from a human placental primer-extended cDNA library which contains a unique
      5' sequence. This cDNA has been isolated and sequences used to screen a human
      placental genomic library for the presence of a unique first exon. The exon (exon
      I.2) lies 9 kb 5' of the second, ATG-containing exon (exon II) and is spliced
      onto exon II at the same site as that reported for exon I.1. DNA sequence
      analysis indicates that exon I.2 has a putative TATA (TAAA) sequence 33 base
      pairs (bp) upstream from a putative transcription start site and putative CAAT
      (CATT) binding sequence beginning at 54 bp upstream from this start site.
      Polymerase chain reaction (PCR) amplification experiments indicate that mRNA
      containing exon I.2-specific sequences can be demonstrated in tissues of fetal,
      but not adult, origin. These data have been confirmed by Northern analysis in the
      placenta. Characterization of this genomic clone containing exons I.2 and II now
      establishes the P-450AROM gene to be at least 72 kb in length and raises new
      questions regarding tissue specific and developmental control of aromatase
      expression in the human.

PMID- 1372569
TI  - The role of the basement membrane in differential expression of keratin proteins
      in epithelial cells.
AB  - Extracellular matrix is considered to play an important role in determining the
      phenotype of cells with which it interacts. Here we have investigated the
      possibility that extracellular matrix is involved in specifying the pattern of
      keratin expression in epithelial cells. For these studies, we have developed an
      explant system in which epithelial cells from one type of stratified epithelial
      tissue, namely conjunctiva, are maintained on an extracellular matrix substrate
      derived from a different tissue, namely cornea. These ocular tissues are ideal
      for such analyses since they express distinct sets of keratins. For example,
      bovine conjunctival epithelium processed for immunofluorescence is not recognized
      by antibody preparations against keratin K3 or K12. In contrast, K3 and K12
      antibodies generate intense staining in bovine corneal epithelium. At the
      immunochemical level, conjunctival cells in situ appear to possess no K12 and
      only trace amounts of K3, whereas corneal epithelial cells in situ possess both
      K3 and K12. When conjunctival cells are maintained on a corneal substrate with an
      intact basement membrane for 10 days in vitro they begin to express keratin K12
      as determined by immunofluorescence. On the other hand, conjunctival cells that
      are maintained on a corneal substrate lacking a basement membrane fail to show
      staining with K12 antibodies. Conjunctival cells begin to show intense staining
      using K3 antibodies within about 10 days of being placed in culture regardless of
      their substrate. These results indicate that basement membrane can play a
      positive role in determining cell-specific expression of certain keratins such as
      K12. However, other keratins such as K3 may be "unmasked" and/or their expression
      may be upregulated simply by placing conjunctival epithelial cells in culture. We
      speculate that in conjunctiva K3 expression is influenced by certain negative
      exogenous factors. We discuss the possible means of regulation of keratin
      expression in our model system.

PMID- 1372570
TI  - Effects of ciliary neurotrophic factor (CNTF) and depolarization on neuropeptide
      expression in cultured sympathetic neurons.
AB  - We examined the effects of ciliary neurotrophic factor (CNTF) and depolarization,
      two environmental signals that influence noradrenergic and cholinergic function,
      on neuropeptide expression by cultured sympathetic neurons. Sciatic nerve
      extract, a rich source of CNTF, increased levels of vasoactive intestinal peptide
      (VIP), substance P, and somatostatin severalfold while significantly reducing
      levels of neuropeptide Y (NPY). No change was observed in the levels of leu
      enkephalin (L-Enk). These effects were abolished by immunoprecipitation of CNTF
      like molecules from the extract with an antiserum raised against recombinant
      CNTF, and recombinant CNTF caused changes in neuropeptide levels similar to those
      of sciatic nerve extract. Alterations in neuropeptide levels by CNTF were dose
      dependent, with maximal induction at concentrations of 5-25 ng/ml. Peptide levels
      were altered after only 3 days of CNTF exposure and continued to change for 14
      days. Depolarization of sympathetic neuron cultures with elevated potassium
      elicited a different spectrum of effects; it increased VIP and NPY content but
      did not alter substance P, somatostatin, or L-Enk. Depolarization is known to
      block cholinergic induction in response to heart cell conditioned medium and we
      found that it blocked the induction of choline acetyltransferase (ChAT) and
      peptides by recombinant cholinergic differentiation factor/leukemia inhibitory
      factor (CDF/LIF). In contrast, it did not antagonize the effects of CNTF on
      either ChAT activity or neuropeptide expression. Thus, while CNTF has effects on
      neurotransmitter properties similar to those previously reported for CDF/LIF, the
      actions of these two factors are differentially modulated by depolarization,
      suggesting that the mechanisms of cholinergic and neuropeptide induction for the
      two factors differ. In addition, in contrast to CDF/LIF, CNTF did not alter
      levels of ChAT, VIP, substance P, or somatostatin in cultured dorsal root
      ganglion neurons. These observations indicate that CNTF and depolarization affect
      the expression of neuropeptides by sympathetic neurons and provide evidence for
      an overlapping yet distinct spectrum of actions of the two neuronal
      differentiation factors, CNTF and CDF/LIF.

PMID- 1372571
TI  - An ecdysteroid-inducible Manduca gene similar to the Drosophila DHR3 gene, a
      member of the steroid hormone receptor superfamily.
AB  - Using cDNAs for the human retinoic acid receptor alpha (hRAR alpha) and
      Drosophila hormone receptor 3 (DHR3), we isolated a cDNA encoding a member of the
      steroid hormone receptor superfamily from the tobacco hornworm, Manduca sexta.
      Sequencing showed that this cDNA is most closely related to DHR3 (97 and 68%
      amino acid identity in the DNA and ligand binding regions, respectively) followed
      by hRAR alpha (65 and 20% identity, respectively) and therefore is named MHR3.
      The cDNA hybridized to two mRNAs (3.8 and 4.5 kb) found in the epidermis during
      the ecdysteroid rises for the embryonic, larval, and pupal molts. Culture of
      fourth instar larval epidermis with 4 microM 20-hydroxyecdysone (2 micrograms/ml
      20HE) caused the appearance of MHR3 mRNA within 3 hr and maximal expression by 6
      hr; after 12 hr continuous exposure to 20HE, the mRNA level declined. The 4.5-kb
      mRNA appeared first, both were present in equal amounts by 12 hr, and by 20 hr
      the predominant transcript was 3.8 kb. Similar 20HE-induced expression was seen
      in epidermis explanted 1 day after the onset of wandering, although with a slower
      time course. The induction was largely independent of protein synthesis, but the
      subsequent decline required protein synthesis as is typical of the "early" puffs
      in Drosophila. Continuous exposure to 20HE was necessary for MHR3 expression; in
      its absence, the mRNA declined with a half-life of 2 hr. Thus, MHR3 is an
      ecdysteroid-inducible DNA binding protein that likely is a transcription factor
      involved in the cascade of gene activation and inactivation caused by
      ecdysteroids during the insect molt.

PMID- 1372572
TI  - Induction of avascular yolk sac due to reduction of basic fibroblast growth
      factor by retinoic acid in mice.
AB  - Vasculogenesis depends on autocrine secretion of basic fibroblast growth factor
      (bFGF) from capillary endothelial cells. Retinoic acid (RA) induced avascular
      yolk sac (AVY) of mouse embryos of dams given 60 mg/kg of RA orally on Day 8 of
      gestation and sacrificed 3 days later. We studied the localization and
      transcriptional expression of bFGF and FGF-receptor (flg), heparin-binding growth
      factor (HBGF) activity, localization of lysosomal enzymes and alpha 1-antitrypsin
      (AAT), and electron microscopy of the normal mouse visceral yolk sac (VYS) and
      AVY. bFGF, which is normally present in the endoderm of the VYS of 8-day-old
      embryos and in all components of the VYS by Day 11 of gestation, was reduced in
      the AVY. However, in the presence of bFGF in vitro capillary nets were restored
      in the AVY. The mRNA for bFGF was not detectable in either VYS or AVY, while flg
      mRNA was detected equally in both organs in Northern blotting. The characteristic
      distribution pattern of lysosomal enzymes, acid phosphatase, lysozyme, and
      cathepsin D, and AAT was altered in the AVY. The level of acid phosphatase and
      AAT was reduced to 10% in the AVY. Electron microscopy revealed a partial or
      total loss of lysosomal membranes where the contents of lysosomes fused with
      adjacent lysosomes and the external organelles. These results suggest that
      vitelline blood vessels are not developed by endogenous autocrine bFGF but by
      exogenous transcellular bFGF from absorptive endodermal cells. Retinoic acid does
      not affect the angiogenic capacity of the VYS mesenchyme but destroys lysosomes,
      which release hydrolytic enzymes, leading to degradation of AAT in the endodermal
      cells and then digestion of endocytosed bFGF.

PMID- 1372573
TI  - Glucose and insulin chronically regulate insulin action via different mechanisms
      in BC3H1 myocytes. Effects on glucose transporter gene expression.
AB  - We previously reported that, in primary cultured adipocytes, chronic exposure to
      glucose plus insulin impairs the insulin-responsive glucose transport system. In
      this study, we examined regulation of glucose transport in BC3H1 myocytes as a
      model for muscle and found important differences between BC3H1 cells and
      adipocytes. In myocytes, chronic glucose exposure per se (25 mM) decreased basal
      glucose transport activity by 78% and insulin's acute ability to maximally
      stimulate transport by 68% (ED50 approximately 2.5 mM; T1/2 approximately 4 h). D
      Mannose and 3-O-methyl-glucose diminished transport rates with approximately 100
      and 50% of the potency of D-glucose, respectively, whereas L-glucose, D-fructose,
      and D-galactose were inactive. Chronic glucose exposure also reduced cell surface
      insulin binding by 30% via an apparent decrease in receptor affinity, and this
      effect was associated with a comparable rightward shift in the insulin-glucose
      transport dose-response curve. In other studies, persistent stimulation with 15
      nM insulin also decreased maximally stimulated glucose transport activity, which
      was independent and additive to the regulatory effect of glucose. Moreover,
      glucose and insulin-induced insulin resistance via different mechanisms. Glucose
      (25 mM) reduced the number of cellular glucose transporter proteins by 84% and
      levels of GLUT1 transporter mRNA by 50% (whether normalized to total RNA or CHO-B
      mRNA). In contrast, chronic insulin exposure led to a 2.1-fold increase in GLUT1
      mRNA but did not alter cellular levels of transporter protein. Cotreatment with
      glucose prevented the insulin-induced rise in GLUT1 mRNA. BC3H1 cells did not
      express GLUT4 mRNA that encodes the major transporter isoform in skeletal muscle.
      In conclusion, in BC3H1 myocytes 1) glucose diminished insulin sensitivity by
      decreasing insulin receptor binding affinity and decreased basal and maximally
      insulin-stimulated glucose transport rates via cellular depletion of glucose
      transporters and suppression of GLUT1 mRNA; 2) chronic insulin exposure exerted
      an independent and additive effect to reduce maximal transport activity; however,
      insulin increased levels of GLUT1 mRNA and did not alter the cellular content of
      glucose transporters; and 3) although BC3H1 cells are commonly used as a model
      for skeletal muscle, studies examining glucose transport should be interpreted
      cautiously due to the absence of GLUT4 expression. Nevertheless, the data
      generally support the idea that, in non-insulin-dependent diabetes mellitus,
      hyperglycemia and hyperinsulinemia can induce or exacerbate insulin resistance in
      target tissues.

PMID- 1372574
TI  - Multiple TCR V beta usage by infiltrates of young NOD mouse islets of Langerhans.
      A polymerase chain reaction analysis.
AB  - Because a restricted repertoire of T-cell receptor (TCR) V beta gene expression
      has been reported in other autoimmune diseases, the possibility of similarly
      restricted V beta gene expression by T-cell infiltrates of NOD mouse islets was
      examined. With isolated islets from 4- to 12-wk-old NOD mice, a prospective
      polymerase chain reaction analysis with 18 V beta-specific oligonucleotide
      primers was performed on the noncloned and unexpanded islet-infiltrating T cells.
      The methodology used permitted the detection of a minimum of 50 T cells. In
      contrast to the restricted TCR V beta gene usage reported for other autoimmune
      diseases, infiltrates of even the youngest mice were characterized by expression
      of multiple V beta gene segments.

PMID- 1372575
TI  - 16,16-Dimethyl prostaglandin E2 reduces bile acid-mediated intestinal vascular
      injury in rats.
AB  - To examine the effects of prostaglandin on bile acid-mediated intestinal vascular
      injury, male rats were given 50 mg/kg of fluorescein isothiocyanate (FITC)
      stained dextran 70 or 25 mg/kg of Evans Blue intravenously. Before intestinal
      injury with 45-minute perfusion of 5 mmol/L chenodeoxycholic acid, rats received
      16,16-dimethyl prostaglandin E2 (5 micrograms/kg intravenously or 0.5
      micrograms/mL or in the perfusate for 15 minutes or vehicle). FITC-dextran
      clearance from the blood to the intestinal lumen and tissue Evans Blue content
      were used as measures of intestinal vascular injury. Morphological mucosal injury
      was assessed by transmission electron microscopy and quantitative histological
      analysis. Chenodeoxycholic acid perfusion caused villous denudation and
      shortening of and ultrastructural damage to villous venules. Functional vascular
      injury was evidenced by a 10-fold increase in the rate of FITC-dextran blood-to
      lumen clearance and a 3-4-fold increase in tissue Evans Blue content.
      Pretreatment with either intravenous or intraluminal 16,16-dimethyl prostaglandin
      E2 reduced FITC-dextran clearance by 70%-80% and tissue Evans Blue content by
      50%. However, only luminal prostaglandin reduced superficial mucosal
      morphological injury, possibly because of differences in the local concentrations
      of 16,16-dimethyl prostaglandin E2 or chenodeoxycholic acid or because of
      superficial mucosal protection and injury being, at least in part, independent of
      mucosal microvascular injury and protection.

PMID- 1372576
TI  - Cyclic interdigestive pancreatic exocrine secretion: is it mediated by neural or
      hormonal mechanisms?
AB  - Cyclic interdigestive exocrine pancreatic secretion and duodenal motility are
      closely linked. However, the mechanisms controlling this association are not well
      understood. The aim of this study was to determine whether a neural or hormonal
      mechanism controls the temporal association of interdigestive secretion and
      duodenal motility. In five dogs, the pancreas was autotransplanted to the pelvis
      with anastomosis of the pancreatic duct orifice to the bladder. Electrodes were
      positioned to monitor motility patterns of the in situ duodenum. After 10 days,
      dogs were studied on four occasions during fasting. Pancreatic output of amylase
      activity continued to cycle, but the periodicity of enzyme peaks (mean +/- SE)
      was different from the period of the duodenal migrating motor complex (MMC) (60
      +/- 3 vs. 125 +/- 7 minutes; P less than 0.05). When grouped according to phase
      of duodenal MMC, amylase output per 10 minutes during phase I was significantly
      less than the outputs during phase II or III (135 +/- 52, 214 +/- 78, and 228 +/-
      73 x 10(3) U; P less than 0.05). However, there was no temporal relationship of
      the cyclic output of amylase to duodenal phase III. No differences were found
      when amylase output was analyzed for the 30 minutes before phase III compared
      with the 30 minutes after phase III (687 +/- 253 vs. 378 +/- 110 x 10(3) U; P
      greater than 0.05). Plasma motilin concentrations varied with duodenal MMC, but
      no relationship existed between plasma motilin or plasma pancreatic polypeptide
      and peaks in amylase output. This study suggests that the close temporal
      coordination of interdigestive pancreatic exocrine secretion and duodenal
      motility is controlled primarily by a neural mechanism.

PMID- 1372577
TI  - Laser therapy: first treatment for the palliation of malignant dysphagia.

PMID- 1372578
TI  - Sequence heterogeneity between the two genes encoding 16S rRNA from the
      halophilic archaebacterium Haloarcula marismortui.
AB  - The halophilic archaebacterium, Haloarcula marismortui, contains two nonadjacent
      ribosomal RNA operons, designated rrnA and rrnB, in its genome. The 16S rRNA
      genes within these operons are 1472 nucleotides in length and differ by
      nucleotide substitutions at 74 positions. The substitutions are not uniformly
      distributed but rather are localized within three domains of 16S rRNA; more than
      two-thirds of the differences occur within the domain bounded by nucleotides 508
      and 823. This domain is known to be important for P site binding of aminoacylated
      tRNA and for 30-50S subunit association. Using S1 nuclease protection, it has
      been shown that the 16S rRNAs transcribed from both operons are equally
      represented in the functional 70S ribosome population. Comparison of these two H.
      marismortui sequences to the 16S gene sequences from related halophilic genera
      suggests that (i) in diverging genera, mutational differences in 16S gene
      sequences are not clustered but rather are more generally distributed throughout
      the length of the 16S sequence, and (ii) the rrnB sequence, particularly within
      the 508-823 domain, is more different from the out group sequences than is the
      rrnA sequence. Several possible explanations for the evolutionary origin and
      maintenance of this sequence heterogeneity within 16S rRNA of H. marismortui are
      discussed.

PMID- 1372579
TI  - Molecular analysis of a Salmonella enterica group E1 rfb gene cluster: O antigen
      and the genetic basis of the major polymorphism.
AB  - Salmonella enterica is highly polymorphic for the O antigen, a surface
      polysaccharide that is subject to intense selection by the host immune system.
      This polymorphism is used for serotyping Salmonella isolates. The genes encoding
      O antigen biosynthesis are located in the rfb gene cluster. We report here the
      cloning and sequence of the 19-kb rfb region from strain M32 (serovar anatum,
      group E1) and compare it with that of strain LT2 (serovar typhimurium, group B).
      Genes for biosynthetic pathways common to both strains are conserved and have
      very similar sequences. In contrast, the five genes for CDP-abequose synthesis,
      present in strain LT2, are absent in strain M32; three open reading frames (ORFs)
      of strain LT2, thought to include genes for transferases, are not present in
      strain M32 but are replaced by three different ORFs with little or low level of
      similarity. Both rfb gene clusters are low in G + C content, indicating that they
      were transferred from a common ancestral species with low G + C content to S.
      enterica relatively recently (in the evolutionary sense). We discuss the
      recombination and lateral transfer events which may have been involved in the
      evolution of the polymorphism.

PMID- 1372580
TI  - Initiator oligonucleotides for the combination of chemical and enzymatic RNA
      synthesis.
AB  - Transcription reactions with T7 RNA polymerase were performed in the presence of
      short oligonucleotides (oligos) with guanosine at the 3'-end. We obtained
      transcripts which had included these 'initiator oligos' at their 5'-termini. The
      oligos could contain mixtures of deoxyribo-, ribo-, 2'-O-methylated and
      biotinylated nucleotides. Only the 3'-terminal guanosine of these oligos was
      encoded in the template DNA at the transcription start point, in contrast to the
      remainder of the sequence. This 5'-terminal sequence is variable and eliminates
      the limitation that transcripts must start with a 5'-terminal guanosine. With a
      5'-biotinylated dinucleotide, we obtained end-labeled RNAs suitable for
      nonradioactive RNA sequencing.

PMID- 1372581
TI  - Vitronectin in liver disorders: biochemical and immunohistochemical studies.
AB  - The concentration of plasma vitronectin was determined and compared with various
      parameters of liver function including the blood coagulation system in patients
      with liver diseases. The severity of cirrhosis was graded according to Child's
      criteria and compared with the plasma vitronectin level. Furthermore, the
      distribution of vitronectin in the liver of patients with liver diseases was
      studied by light and electron microscopy using the indirect immunoperoxidase
      method. The plasma vitronectin level was low in all liver disease groups as
      compared with the healthy controls. The difference from the controls was
      significant in patients with hepatocellular carcinoma and decompensated
      cirrhosis. Moreover, the plasma vitronectin level was positively correlated with
      the levels of serum cholinesterase, albumin, plasma alpha 2 plasmin inhibitor
      plasmin complex and the prothrombin time and results of the hepatoplastin test.
      Plasma vitronectin decreased with increasing severity of cirrhosis according to
      Child's criteria. These results suggest that the plasma vitronectin level is a
      useful parameter of hepatic synthetic function in patients with liver diseases;
      it may also reflect the severity of cirrhosis. Light microscopy revealed
      vitronectin in the area of focal necrosis and the portal tracts in the liver of
      patients with acute viral hepatitis, in the area of piecemeal necrosis in the
      liver of patients with chronic hepatitis and along the area of fiber deposition
      in the liver of patients with cirrhosis. Immunoelectron microscopy showed
      vitronectin in the rough endoplasmic reticulum of hepatocytes. Moreover,
      vitronectin was seen around inflammatory cells, endothelial cells, Ito cells and
      hepatocytes in the perisinusoidal area near focal necrosis and piecemeal necrosis
      and on collagen fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372582
TI  - Evaluation of hepatitis delta virus RNA levels during interferon therapy by
      analysis of polymerase chain reaction products with a nonradioisotopic
      hybridization assay.
AB  - We developed a nonradioisotopic assay for detection of hepatitis delta virus RNA
      in serum by combining reverse transcription of RNA, polymerase chain reaction of
      the resultant complementary DNA and enzyme linked immunoassay detection of the
      polymerase chain reaction products using a monoclonal antibody specific for
      double-stranded DNA. This DNA enzyme immunoassay had a limit of detection of
      cloned hepatitis delta virus RNA similar to that of standard PCR followed by
      Southern-blot hybridization (approximately 10 copies/sample) and was 10(3) to
      10(4) times more sensitive than direct dot-blot hybridization (approximately
      10(5) copies/sample). Serial serum samples from six patients with chronic
      hepatitis delta virus infection undergoing interferon therapy were analyzed by
      reverse transcription-polymerase chain reaction followed by both standard
      hybridization and DNA enzyme immunoassay. The results of both methods were
      comparable, revealing disappearance of hepatitis delta virus RNA after 3 to 6 mo
      of therapy in three patients, two of whom had also a significant decrease in ALT
      activity. The DNA enzyme immunoassay test is therefore a potentially useful
      method for therapeutic monitoring in chronic hepatitis delta virus infection and
      may contribute to a wider application of polymerase chain reaction in clinical
      laboratories.

PMID- 1372583
TI  - Abnormal surface distribution of the human asialoglycoprotein receptor in
      cirrhosis.
AB  - Serum concentrations of asialoglycoproteins are increased in cirrhosis. We
      hypothesized that this increase results from abnormalities in the
      asialoglycoprotein receptor, which is located on the sinusoidal and lateral
      membrane of hepatocytes. Therefore we searched for morphological alterations in
      the distribution of the asialoglycoprotein receptor in human liver, using a light
      microscopic immunoperoxidase method in autopsy livers. In 24 of 25 (96%) of
      patients without liver disease, the asialoglycoprotein receptor was located on
      the sinusoidal and, less prominently, the lateral surface of hepatocytes but not
      the canalicular surface. In contrast, in 12 of 18 (67%) patients with cirrhosis
      of various causes, the receptor also was localized strikingly along the
      canalicular surface, with a corresponding decrease on the sinusoidal and lateral
      surfaces. We conclude that an abnormal cell-surface distribution of the
      asialoglycoprotein receptor commonly occurs in cirrhosis. This abnormality might
      result in impaired clearance of desialylated glycoproteins from plasma.

PMID- 1372584
TI  - Hepatocyte regeneration in acute fulminant and nonfulminant hepatitis: a study of
      proliferating cell nuclear antigen expression.
AB  - It has been suggested that in fulminant hepatitis it is the lack of hepatocyte
      regeneration that in the presence of an ongoing loss of hepatocytes leads to
      hepatic failure and ultimately determines the grim prognosis of this disease.
      However, little data are available concerning hepatocyte regeneration in human
      acute hepatitis. We compared the nuclear expression of proliferating cell nuclear
      antigen with the incorporation of bromodeoxyuridine in formalin-fixed, paraffin
      embedded liver tissues of rats at different stages of regeneration after two
      thirds partial hepatectomy. Immunohistochemical staining for proliferating cell
      nuclear antigen was performed using the monoclonal antibody 19F4. A good
      correlation was seen between nuclear labeling for bromodeoxyuridine and
      proliferating cell nuclear antigen, which indicates that the immunoreactivity for
      proliferating cell nuclear antigen accurately reflects hepatocyte proliferation.
      Subsequently, we determined the nuclear expression of proliferating cell nuclear
      antigen on archival paraffin-embedded samples of the normal human liver (8
      cases), acute nonfulminant hepatitis (10 cases) and fulminant hepatitis (4
      cases). The mean proliferating cell nuclear antigen labeling indices were the
      following: normal liver = 0.4%; acute nonfulminant hepatitis = 43.0%; and
      fulminant hepatitis = 45.9%. The indices for proliferating cell nuclear antigen
      were significantly greater in acute hepatitis than in the normal liver,
      reflecting the high cell turnover in hepatitis. However, no significant
      difference was seen between the expression of proliferating cell nuclear antigen
      in nonfulminant and fulminant acute hepatitis. These data suggest that the net
      loss of hepatocytes in fulminant hepatitis may not be caused by a lack of
      hepatocyte regeneration but rather results from overwhelming hepatocyte injury
      with subsequent cell death.

PMID- 1372585
TI  - Complementation study of peroxisome-deficient disorders by immunofluorescence
      staining and characterization of fused cells.
AB  - Genetic heterogeneity in peroxisome-deficient disorders, including Zellweger's
      cerebrohepatorenal syndrome, neonatal adrenoleukodystrophy and infantile Refsum
      disease, was investigated. Fibroblasts from 17 patients were fused using
      polyethylene glycol, cultivated on cover slips, and the formation of peroxisomes
      in the fused cells was visualized by immunofluorescence staining, using anti
      human catalase IgG. Two distinct staining patterns were observed: (1) peroxisomes
      appeared in the majority of multinucleated cells, and (2) practically no
      peroxisomes were identified. Single step 12-(1'-pyrene) dodecanoic
      acid/ultraviolet (P12/UV)-selection confirmed that the former groups were
      resistant to this selection, most of the surviving cells contained abundant
      peroxisomes, and the latter cells died. In the complementary matching, [1
      14C]lignoceric acid oxidation and the biosynthesis of peroxisomal proteins were
      also normalized. Five complementation groups were identified. Group A: Zellweger
      syndrome and infantile Refsum disease; Groups B, C and D: Zellweger syndrome;
      Group E: Zellweger syndrome, neonatal adrenoleukodystrophy and infantile Refsum
      disease. We compared these groupings with those of Roscher and identified eight
      complementation groups. There was no obvious relation between complementation
      groups and clinical phenotypes. These results indicate that the transport,
      intracellular processing and function of peroxisomal proteins were normalized in
      the complementary matching and that at least eight different genes are involved
      in the formation of normal peroxisomes and in the transport of peroxisomal
      enzymes.

PMID- 1372586
TI  - CFTR illegitimate transcription in lymphoid cells: quantification and
      applications to the investigation of pathological transcripts.
AB  - Since the isolation of the cystic fibrosis transmembrane conductance regulator
      gene (CFTR) and the characterization of the main mutation (delta F508) in 1989, a
      large number of rare mutations has been found. Full screening of the CFTR gene is
      difficult because it is split into 27 exons covering 250 kb of genomic DNA. This
      gene is essentially expressed in the lung and intestinal tract, neither of which
      are easily accessible for routine investigations. The recent description of a
      faint transcription of highly tissue-specific genes in any cell, a phenomenon
      known as illegitimate transcription, would facilitate the research of mutations
      and the characterization of truncated m-RNA caused by splicing mutations. Using
      the polymerase chain reaction on cDNA (cDNA-PCR), we detected transcripts of the
      CFTR gene in lymphocytes and lymphoblast cells at a very low level (about 300
      times less than in lung or intestine). This strategy allowed us to obtain a
      sufficient amount of cDNA-PCR product compatible with further molecular analyses.
      We have, therefore, analyzed a cDNA fragment overlapping exons 10 and 11 by
      polyacrylamide gel electrophoresis and direct sequencing, and detected the delta
      F508 mutation at this level. Our protocol can be generalized to the investigation
      of the total 4.5-kb CFTR coding sequence.

PMID- 1372587
TI  - Nested polymerase chain reaction on cellular DNA in plasma: a rapid method to
      investigate the collagen type I A2 MspI polymorphic restriction site in alcoholic
      patients.
AB  - We investigated the MspI restriction site of the human collagen type I A2
      (COL1A2) gene in alcoholic subjects with and without liver disease, using the
      nested polymerase chain reaction to analyse trace cellular DNA in plasma samples.
      This procedure is rapid, it requires only 200 microliters plasma, and the results
      correlate perfectly with those of Southern blotting. Alcoholic subjects with
      acute alcoholic hepatitis had a significantly lower frequency of the minor allele
      than healthy controls or alcoholics with minimal liver abnormalities, i.e.
      steatosis. Our results reinforce the hypothesis of a genetic predisposition of
      certain alcoholics to liver damage.

PMID- 1372589
TI  - Identification of the immunoglobulin binding regions (IBR) of Fc gamma RII and Fc
      epsilon RI.

PMID- 1372588
TI  - The human vitronectin (complement S-protein) gene maps to the centromeric region
      of 17q.
AB  - Vitronectin (complement S-protein, serum-spreading factor, epibolin) is a
      multifunctional glycoprotein that mediates cell-to-substrate adhesion, inhibits
      the cytolytic action of the terminal complement cascade in vitro and binds to
      several serine protease inhibitors of the serpin family, viz. antithrombin III,
      plasminogen activator inhibitor I (PAI-1) and II (PAI-2), heparin cofactor II and
      protease nexin. Using high resolution fluorescence in situ hybridization, we
      mapped the vitronectin gene to the centromeric region of the long arm of
      chromosome 17 corresponding to 17q11. The location was confirmed by co
      hybridization with the centromere-specific alphoid probe p17H8 (D17Z1) and by
      chromosome banding with 4,6-diamidino-2-phenylindole-dihydrochloride (DAPI). None
      of the previously mapped genes that are evolutionary related to vitronectin are
      located on the same chromosome.

PMID- 1372590
TI  - The low-affinity receptor for IgE.

PMID- 1372591
TI  - The effect of neonatal tolerance to bovine gamma globulin (BGG) on BGG-reactive
      CD4+ T lymphocytes.
AB  - Compelling evidence has been presented that tolerance to major histocompatibility
      complex (MHC) and other antigens expressed on cells of the thymus is due to
      clonal deletion. However, it has not been determined conclusively how tolerance
      to diverse antigens, which may initially interact with the immune system in the
      periphery, is induced and maintained. Considerable evidence exists to suggest
      that mechanisms other than deletion, such as clonal anergy or immunoregulation,
      may be involved. We have previously shown that the clonal deletion of CD4+ cells
      specific for bovine gamma globulin (BGG) does not occur during induction of
      tolerance to this soluble antigen in adult life. In this study we have extended
      our previous findings by examining unresponsiveness to BGG which had been
      established during early ontogeny, when natural tolerance of self-antigens is
      likely to develop. It is demonstrated here that BGG-reactive, CD4+8- T cells,
      which proliferate and secrete interleukin-2 on stimulation with BGG in vitro, can
      be obtained from mice rendered tolerant of BGG as neonates. Even though the mice
      from which they were derived were unable to respond to BGG, these BGG-reactive T
      cells, by the parameters tested here, could not readily be distinguished from the
      corresponding cells in BGG-immune and non-immune animals. It is therefore evident
      that this tolerant state is not simply the result of clonal deletion of BGG
      reactive CD4+ T cells but is more likely to be due to a reversible mechanism
      which controls their responsiveness in vivo.

PMID- 1372593
TI  - Antibodies to hepatitis C virus in blood donors.

PMID- 1372592
TI  - Expression and function of membrane attack complex inhibitory proteins on thyroid
      follicular cells.
AB  - Human thyroid cells are resistant to lysis by the homologous membrane attack
      complex. By immunohistochemical staining we here show that normal thyroid cells
      and those in Graves' disease and Hashimoto's thyroiditis express two membrane
      attack complex-inhibiting proteins, CD59 antigen and membrane attack complex
      inhibiting protein/homologous restriction factor (MIP/HRF). In vitro, the
      expression of both molecules was enhanced by interleukin-1 (IL-1), tumour
      necrosis factor (TNF) and interferon-gamma (IFN-gamma) and cytokine-treated
      thyroid cells were more resistant to lysis by homologous complement. Blocking
      experiments with monoclonal antibodies against CD59 antigen and MIP/HRF showed
      that both molecules contributed but CD59 antigen was the more important in
      mediating resistance to complement attack. Expression of these proteins may be an
      important determinant of the severity of tissue injury produced by complement
      fixing thyroid peroxidase antibodies in autoimmune thyroid disease.

PMID- 1372594
TI  - [Pathophysiologic mechanisms of atherogenesis with special reference to lipid
      metabolism].

PMID- 1372596
TI  - Staining of hyaluronan in rat cerebellum with a hyaluronectin-antihyaluronectin
      immune complex.
AB  - The presence of hyaluronan was studied histochemically in the adult rat
      cerebellum. We used the hyaluronectin--antihyaluronectin immune complex technique
      based on the high affinity of hyaluronectin for hyaluronan. The immune complex
      was prepared with hyaluronectin from a human brain extract and an anti
      hyaluronectin monoclonal antibody, which does not react with rat hyaluronectin.
      This is a specific probe for detecting hyaluronan in rat tissues without any
      reaction for tissue hyaluronectin. Hyaluronan was found at the nodes of Ranvier,
      in the perineuronal microenvironment of the deep nuclei and at the Purkinje cells
      surrounding the initial segment of the axon. It was located at the same places as
      hyaluronectin, in areas specialized in ion exchanges and neurotransmission. This
      suggests that the hyaluronectin-hyaluronan complex could be involved in these
      processes. The immune complex technique with anti-hyaluronectin monoclonal
      antibody thus seems to be a specific and valuable tool for investigations of the
      distribution of hyaluronan in the rat cerebellum.

PMID- 1372595
TI  - Increased expression of highly branched N-linked oligosaccharides terminating in
      N-acetylglucosamine residues in neoplastic and sclerodermal chicken fibroblasts.
AB  - Although neoplastic cells often show a shift towards the expression of larger N
      linked oligosaccharides compared to their normal counterparts, little
      consideration has been given to the possibility that these changes might be a
      more general phenomenon characteristic of certain neoplastic and non-neoplastic
      proliferative disorders. Terminal N-acetylglucosamine (GlcNAc) cluster antigen
      (TGCA) is an immunoreactive epitope(s) of highly branched N-linked
      oligosaccharides terminating in GlcNAc residues. Here we have compared the
      expression of this antigen in normal, neoplastic and sclerodermal chicken
      fibroblasts by immunomorphological methods. TGCA was detectable in only a few, if
      any, fibroblasts of normal chicken skin or those cultured from chicken embryos.
      In contrast, the antigen appeared in 15 to 30% of chicken embryo fibroblasts
      transformed with avian sarcoma viruses and about 50% of neoplastic fibroblasts of
      both Rous sarcoma virus-induced fibrosarcomas and carcinogen-induced
      transplantable fibrosarcomas. Significantly, TGCA was also found in most
      activated fibroblasts in the skin of chickens with hereditary scleroderma. These
      results indicate that increased expression of highly branched N-linked
      oligosaccharides terminating in GlcNAc residues is characteristic of both
      neoplastic and sclerodermal chicken fibroblasts. Investigation of this phenomenon
      may thus provide insight into biochemical pathways involved in neoplastic
      transformation and pathogenesis of a number of non-neoplastic proliferative
      connective tissue disorders such as scleroderma. Moreover, changes in the
      expression of TGCA-positive oligosaccharides (or their modified biochemical
      counterparts in mammalian species) may have considerable value for diagnosis of
      several connective tissue diseases.

PMID- 1372598
TI  - Detection and quantitation of sperm-bound antibodies by flow cytometry of human
      semen.
AB  - Detection of sperm surface antibodies is important for the diagnosis and
      treatment of infertility. The authors have investigated the methodologic aspects
      of flow cytometry (FCM) to detect sperm-bound antibodies and to quantitate the
      sperm antibody load (antibody molecules/spermatozoa). To obtain reliable results,
      dead spermatozoa must be excluded from analysis because they can bind antibody
      nonspecifically, and comprise 10% to 58% (n = 28) of the ejaculate in subfertile
      men. Flow cytometry estimation of dead cells correlates (r = 0.83) significantly
      with the manual Eosin Y method. After staining washed sperm samples (n = 26) with
      fluorescein-isothiocyanate-conjugated F(ab')2 fragments of anti-IgG and IgA
      antibodies, the sperm load was 11,500 +/- 8,600 IgG molecules and 13,200 +/-
      9,500 IgA molecules per spermatozoa. The sperm antibody load measured on
      different occasions could be compared between patients or in the same patient by
      the use of calibration standards. Since the inter- and intra-assay variation of
      the FCM assays was less than 10%, FCM has the potential reliably and objectively
      to monitor the sperm antibody load during corticosteroid treatment.

PMID- 1372597
TI  - Co-expression of vimentin and cytokeratins in M cells of rabbit intestinal
      lymphoid follicle-associated epithelium.
AB  - Membranous epithelial (M) cells within the follicle-associated epithelium which
      overlies gut-associated lymphoid tissue in Peyer's patches and of appendix have
      been shown by immunocytochemical staining, in rabbit, to contain both vimentin-
      and cytokeratin-type intermediate filaments. The specificity of vimentin
      immunostaining has been confirmed by blocking with purified vimentin and by
      immunoblotting. No evidence was obtained for the expression of vimentin in rat,
      mouse or human M cells. The possible significance of vimentin-expression in these
      specialized epithelial cells and the potential use of vimentin as a positive
      marker for M cells are discussed.

PMID- 1372599
TI  - Monoclonal antibodies as probes to examine serotype-specific and cross-reactive
      epitopes of lipopolysaccharides from serotypes O2, O5, and O16 of Pseudomonas
      aeruginosa.
AB  - Serotypes O2, O5, and O16 of Pseudomonas aeruginosa are chemically related, and
      the O antigens of their lipopolysaccharides share a similar trisaccharide repeat
      backbone structure. Serotype-specific monoclonal antibodies (MAbs) MF71-3, MF15
      4, and MF47-4 against the O2, O5, and O16 serotypes, respectively, were isolated.
      MAb 18-19, which is cross-reactive with all strains of this chemically related
      serogroup, was also produced. When column chromatography or sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis-separated lipopolysaccharide (LPS)
      samples from each of the serotypes were probed with the MAbs in Western
      immunoblots, each of the serotype-specific MAbs interacted only with high
      molecular-weight bands of the homologous LPS, with a minimum O-antigen chain
      length of at least 6 to 10 repeats. In contrast, cross-reactive MAb 18-19 was
      shown to interact in Western immunoblots with the entire LPS banding pattern
      except the fastest-running band, which lacks O antigen. Chemical modification of
      P. aeruginosa LPS by alkali treatment and carboxyl reduction abolished reactions
      between LPS and MAb 18-19, while reactions of modified LPS with serotype-specific
      MAbs were not affected. Therefore, cross-reactive MAb 18-19 likely recognizes the
      chemical backbone structure of the O repeat that is common to all three serotypes
      of the O2-O5-O16 group, while the O-specific MAbs appeared to recognize LPS
      epitopes that could be presented when 6 to 10 or more O-antigen repeat units are
      present on the LPS molecule. Thus, the O-specific LPS epitopes likely involve
      unique chemical structures, glycosidic linkages, and some order of folding of the
      O side chains.

PMID- 1372600
TI  - Small cytoplasmic RNA of Bacillus subtilis: functional relationship with human
      signal recognition particle 7S RNA and Escherichia coli 4.5S RNA.
AB  - Small cytoplasmic RNA (scRNA; 271 nucleotides) is an abundant and stable RNA of
      the gram-positive bacterium Bacillus subtilis. To investigate the function of
      scRNA in B. subtilis cells, we developed a strain that is dependent on isopropyl
      beta-D-thiogalactopyranoside for scRNA synthesis by fusing the chromosomal scr
      locus with the spac-1 promoter by homologous recombination. Depletion of the
      inducer leads to a loss of scRNA synthesis, defects in protein synthesis and
      production of alpha-amylase and beta-lactamase, and eventual cell death. The loss
      of the scRNA gene in B. subtilis can be complemented by the introduction of human
      signal recognition particle 7S RNA, which is considered to be involved in protein
      transport, or Escherichia coli 4.5S RNA. These results provide further evidence
      for a functional relationship between B. subtilis scRNA, human signal recognition
      particle 7S RNA, and E. coli 4.5S RNA.

PMID- 1372601
TI  - Chemical characterization of pH-dependent structural epitopes of
      lipopolysaccharides from Rhizobium leguminosarum biovar phaseoli.
AB  - Lipopolysaccharide (LPS) was isolated from free-living Rhizobium leguminosarum
      bv. phaseoli CE3 cells grown at pH 4.8 (antigenically similar to bacteroid LPS)
      and compared with that from cells grown at pH 7.2 (free-living bacteria).
      Composition analysis revealed that pH 7.2 LPS differs from pH 4.8 LPS in that
      2,3,4-tri-O-methylfucose is replaced by 2,3-di-O-methylfucose. The amount of 2-O
      methylrhamnose is greater in the pH 4.8 LPS than in the pH 7.2 LPS. Analysis of
      the structural components of LPS (O-chain polysaccharide, core oligosaccharides,
      and the lipid A) revealed that all the composition differences in the various
      LPSs occur in the O-chain polysaccharide. These structural variations between pH
      4.8 and pH 7.2 LPSs provide a chemical basis for the observed lack of cross
      reactivity with pH 4.8 LPS of two monoclonal antibodies, JIM28 and JIM29, raised
      against free-living bacteria grown at pH 7.2. An LPS preparation isolated from
      bacteroids contained both 2,3,4-tri-O- and 2,3-di-O-methylfucose residues. This
      result is consistent with the finding that the two monoclonal antibodies react
      weakly with bacteroid LPS. It is concluded that methylation changes occur on the
      LPS O-chain of R. leguminosarum bv. phaseoli when the bacteria are grown at low
      pH and during nodule development.

PMID- 1372602
TI  - Characterization of the Lactococcus lactis lactose operon promoter: contribution
      of flanking sequences and LacR repressor to promoter activity.
AB  - We determined the location, activity, and regulation of the promoter of the
      Lactococcus lactis 8-kb lactose operon (lacABCDFEGX), which encodes the enzymes
      of the lactose phosphotransferase system and the tagatose 6-phosphate pathway.
      The lac promoter sequence corresponds closely to the consensus promoter described
      for gram-positive bacteria and is located in a back-to-back configuration with
      the promoter of the divergently transcribed lacR gene, which encodes the LacR
      repressor. The transcription start sites used under induced (lactose) and
      noninduced (glucose) conditions were determined. The minimal promoter region that
      could be isolated on a single restriction fragment included sequences ranging
      from -75 to +42. The effect of the presence of flanking sequences and the lacR
      gene on promoter activity and regulation was studied in Escherichia coli and L.
      lactis strains by using transcriptional fusions with promoterless chloramphenicol
      acetyltransferase reporter genes. The results showed that transcriptional
      regulation of the lac operon is mediated by the interaction between the LacR
      repressor, the lac promoter, and sequences in the noncoding region between the
      lacR and lacA genes. Sequences flanking the minimal promoter region appeared to
      enhance lac promoter activity much more in L. lactis (5- to 38-fold) than in E.
      coli (1.3- to 5-fold).

PMID- 1372603
TI  - Mutations affecting translational coupling between the rep genes of an IncB
      miniplasmid.
AB  - The nature of translational coupling between repB and repA, the overlapping rep
      genes of the IncB plasmid pMU720, was examined. Mutations in the start codon of
      the promoter proximal gene, repB, reduced the efficiency of translation of both
      rep genes. Moreover, there was no independent initiation of repA translation in
      the absence of repB translation. The position of the repB stop codon was crucial
      for the efficient expression of repA, with the wild-type positioning being
      optimal. Translational coupling was found to be totally dependent on the
      formation of a pseudoknot structure. A model which invokes formation of a
      pseudoknot to facilitate initiation of repA is proposed.

PMID- 1372605
TI  - Recombinant synthesis, purification, and nucleotide binding characteristics of
      the first nucleotide binding domain of the cystic fibrosis gene product.
AB  - The majority of mutations which lead to clinical cystic fibrosis are located
      within the two predicted nucleotide binding domains of the cystic fibrosis gene
      product. We have used a prokaryotic expression system to synthesize and purify
      the first nucleotide binding domain (NBD-1, amino acids 426-588) with and without
      the most common mutation associated with the disease (the deletion of
      phenylalanine at position 508, delta F508). Both wild type and delta F508 NBD-1
      bind ATP-agarose in a quantitatively comparable manner; this binding was
      inhibited by excess Na2ATP, trinitrophenol-ATP, or 8-azido-ATP. Irreversible NBD
      1 labeling by an ATP analog was demonstrated using [32P]8-azido-ATP. This
      covalent labeling was inhibited by preincubation with Na2ATP, with half-maximal
      inhibition for Na2ATP occurring at approximately 5 mM for both the wild type and
      delta F508 nucleotide binding domain. These experiments are among the first to
      confirm the expectation that the cystic fibrosis transmembrane conductance
      regulator NBD-1 binds nucleotide. Since, under the conditions used in our study,
      NBD-1 without phenylalanine 508 displays very similar nucleotide binding
      characteristics to the wild type protein, our results support previous structural
      models which predict that the delta F508 mutation should not cause an alteration
      in ATP binding.

PMID- 1372604
TI  - Similarity between the Myxococcus xanthus and Stigmatella aurantiaca reverse
      transcriptase genes associated with multicopy, single-stranded DNA.
AB  - To determine the evolutional relationship of bacterial retroelements of
      Myxococcus xanthus and Stigmatella aurantiaca, the nucleotide sequence of 3,060
      bases encompassing msr, msd, and the upstream region of msd (downstream of msr)
      of S. aurantiaca DW4 was determined and compared with the same region from M.
      xanthus. An open reading frame was found 92 bases upstream of msd which encoded a
      polypeptide of 480 amino acid residues having 73% identity with the reverse
      transcriptase of M. xanthus. Together with high homologies in msr (86%) and msd
      (81%) regions, the present data indicate that the reverse transcriptase genes as
      well as the retrons of M. xanthus (retron-Mx162) and S. aurantiaca (retron-Sa163)
      were derived from a common progenitor retron which possibly before the two
      myxobacterial species diverged.

PMID- 1372607
TI  - Unfolding intermediates of the extracellular domain of the interferon gamma
      receptor.
AB  - Reduction of proteins which require disulfide bonds to be stable in the folded
      state is accompanied by step-wise unfolding. A soluble human interferon gamma
      receptor produced in Escherichia coli was used to investigate the kinetics of
      formation of unfolding intermediates. The protein includes 8 cysteine residues
      forming four disulfide bonds. It was reduced by using either dithiothreitol or
      the thioredoxin reduction system. Reduction with dithiothreitol resulted in
      formation of mainly four monomeric unfolding species as visualized by sodium
      dodecyl sulfate-polyacrylamide gels. The enzymatically catalyzed reaction
      produced only small amounts of two monomeric products and mostly delivered
      oligomeric and polymeric forms. In both cases, the ligand binding capacity of the
      receptor was significantly reduced immediately after appearance of the first
      intermediate. The intermediates involved interchange of disulfide bonds and did
      not show ligand binding capacity. Some of them were recognized by specific
      antibodies which detect conformational epitopes on the native interferon gamma
      receptor. On the basis of the antibody binding, a preliminary characterization of
      the formed intermediates was attempted. When the soluble receptor was reduced in
      the presence of denaturing agents, the reduction products were different from the
      unfolding intermediates generated in the absence of denaturants.

PMID- 1372606
TI  - Cloning and expression of a cDNA for mouse prostaglandin E receptor EP3 subtype.
AB  - A functional cDNA clone for mouse EP3 subtype of prostaglandin (PG) E receptor
      was isolated from a mouse cDNA library using polymerase chain reaction based on
      the sequence of the human thromboxane A2 receptor and cross-hybridization
      screening. The mouse EP3 receptor consists of 365 amino acid residues with
      putative seven-transmembrane domains. The sequence revealed significant homology
      to the human thromboxane A2 receptor. Ligand binding studies using membranes of
      COS cells transfected with the cDNA revealed specific [3H]PGE2 binding. The
      binding was displaced with unlabeled PGs in the order of PGE2 = PGE1 greater than
      iloprost greater than PGF2 alpha greater than PGD2. The EP3-selective agonists,
      M&B 28,767 or GR 63799X, potently competed for the [3H]PGE2 binding, but no
      competition was found with EP1- or EP2-selective ligands. PGE2 and M&B 28,767
      decreased forskolin-induced cAMP formation in a concentration-dependent manner in
      Chinese hamster ovary cells permanently expressing the cDNA. Northern blot
      analysis demonstrated that the EP3 mRNA is expressed abundantly in kidney,
      uterus, and mastocytoma P-815 cells and in a lesser amount in brain, thymus,
      lung, heart, stomach, and spleen.

PMID- 1372608
TI  - Functional analysis of regulatory regions upstream and in the first intron of the
      estrogen-responsive chicken very low density apolipoprotein II gene.
AB  - Estrogen regulates the expression of the yolk protein genes in the chicken liver
      during periods of egg laying. While all five of these genes, vitellogenins I, II,
      and III, very low density apolipoprotein II (apo VLDLII), and apolipoprotein B,
      respond to estrogen, individual controls are superimposed on their coordinate
      regulation with respect to the kinetics of induction, magnitude of response, and
      developmental expression. The estrogen-responsive Leghorn strain M hepatoma (LMH)
      cell line provides a model system for studying the molecular basis of the
      similarities and differences in the regulation of these genes. The apoVLDLII gene
      is regulated by estrogen in LMH cells in an appropriate time- and dose-dependent
      manner. Regulatory regions of the apoVLDLII gene have been identified by
      transient transfection studies in LMH cells. All four of the sequences previously
      shown to bind protein between the TAATA motif at -26 and proximal estrogen
      response element at -171 are essential in regulation of the apoVLDLII gene.
      Mutation of any single binding region reduces expression by more than 80%,
      indicating cooperative interactions of proteins across the entire region. While
      these sequences will direct assembly of a functional transcription complex, we
      demonstrate that addition of the first intron of the apoVLDLII gene to the
      promoter construct results in a 4-fold increase in estrogen-dependent expression
      following transient transfection into LMH cells. Results of deletion analyses
      indicate that two distinct regions of the intron contribute to this regulation.

PMID- 1372609
TI  - Lack of agonistic activity in McN-A343 may be circumstantial.
AB  - 1. In Tyrode (Ca++ 1.80 mM) or Krebs (Ca++ 3.36 mM) solution, McN-A343 evoked a
      dose-dependent contractile response in the naive guinea-pig ileum in the dose
      range 0.40-40 microM, or bladder in the dose range 0.8-200 microM. 2. After two
      full cycles of carbachol or bethanechol administration in Tyrode solution,
      neither preparation responded to McN-A343 for 45 to 60 min. The response in Krebs
      solution, however, was almost unaltered at 15-30 min. The rate of recovery of the
      contractile response appears to depend on the calcium content of the medium used.
      3. A previous report that McN-A343 failed to evoke a contractile response in the
      guinea-pig ileum or bladder must be reconsidered in the light of the present
      findings.

PMID- 1372610
TI  - Regional differentiation of gastric and of pyloric smooth muscle in the pig:
      mechanical responses to acetylcholine, histamine, substance P, noradrenaline and
      adrenaline.
AB  - 1. Mechanical activity was recorded in isolated muscle preparations from the
      circular and longitudinal layers of different regions of porcine stomach and from
      the pyloric ring. 2. In all gastric strips acetylcholine (10(-7)-10(-4) mol l-1),
      histamine (10(-7)-10(-5) mol l-1) and substance P (10(-9)-10(-7) mol l-1)
      elicited contractions. 3. In fundic strips the catecholamines, noradrenaline and
      adrenaline (10(-8)-10(-5) mol l-1), produced inhibitory responses at lower
      concentrations and excitatory responses at high concentrations. After blockade of
      beta-adrenoceptors by propranolol, a pure excitatory response remained which
      could be inhibited by alpha-adrenoceptor blockade with phentolamine. No responses
      were observed in corpus and antrum. 4. Strong contractions were induced by these
      catecholamines in circular muscle strips of the pyloric ring, in contrast to
      previous findings reported for human and canine preparations. The contractile
      response of strips from the inner layer of the pyloric ring corresponded to an
      average shortening of 25-30% of resting length, at a concentration of 10(-5) mol
      l-1 of noradrenaline or adrenaline. The responses of preparations from the outer
      layer of the pyloric ring were similar to those of the inner layer but generally
      weaker. The excitatory responses to the catecholamines were totally suppressed by
      10(-5) mol l-1 phentolamine or prazosin but remained unaltered after pretreatment
      with 10(-5) mol l-1 propranolol or 10(-6) mol l-1 yohimbine, which indicates that
      they are mediated by alpha 1-adrenoceptors. 5. Application of substance P (10(-7)
      mol l-1) in the pyloric preparations caused a contraction as strong as that
      induced by noradrenaline or adrenaline. However, histamine, which is known to
      induce strong contractions in canine pylorus, had--as in human pylorus--no effect
      on porcine pylorus at concentrations up to 10(-5) mol l-1.

PMID- 1372613
TI  - Use of non-neutralizing monoclonal antibodies in an ELISA for intratypic
      differentiation of 28 echovirus type 25 clinical isolates.
AB  - Three non-neutralizing monoclonal antibodies were produced and selected against
      echovirus type 25 JV-4 prototype strain. They were used in an ELISA to
      investigate the intratypic differentiation of 28 wild isolates. Clinical isolates
      fell into seven different groups according to their reactivity patterns in ELISA.
      Two of the non-neutralizing monoclonal antibodies, 9E4 and 6D3, were highly
      specific, while the third, 6C9, may recognize an epitope common to other types of
      echoviruses. In contrast, mouse polyclonal antiserum exhibited large cross
      reactivities among echovirus serotypes. The reactivity patterns and the
      geographical origin of the isolates were generally not correlated and, in the
      same area, four major antigenic variants sometimes coexisted, especially in the
      south of France. Moreover, reactivity patterns found with ELISA were hardly ever
      correlated with those observed in a previous study when neutralization tests were
      used. These results again underline the non-correlation between structure and
      biological function in the Picornavirus family.

PMID- 1372611
TI  - Development and characterization of human anti-HBs antibodies.
AB  - Peripheral blood mononuclear cells (PBMC) from 13 healthy hepatitis B vaccines
      were transformed with the Epstein-Barr virus (EBV) and lymphoblastoid cell lines
      (LCL) producing antibodies to hepatitis B surface antigen (anti-HBs antibodies).
      Seven LCL and two clones secreting human anti-HBs monoclonal antibody were
      generated and their antibodies purified. One clone was fused with a mouse myeloma
      and the antibody from a cloned anti-HBs secreting heterohybridoma purified. One
      of the 10 purified human anti-HBs antibodies was characterized as IgG4, the
      remainder were IgG1. The antibodies had either kappa or lambda light chains. Five
      of the antibodies which were conjugated to horseradish peroxidase recognised the
      "a" group determinants.

PMID- 1372612
TI  - Use of bacterial trpE fusion vectors to express and characterize the bovine
      immunodeficiency-like virus core protein.
AB  - The gag coding region from Bovine Immunodeficiency-like Virus (BIV) was cloned
      into E. coli and expressed as a bacterial fusion protein. Six different clones
      spanning various regions of the gag open reading frame were generated. The
      resulting fusion proteins were expressed at high concentrations and readily
      purified. A panel of bovine immune sera specifically recognized the recombinant
      Gag proteins, as did immune sera from animals infected or immunized with
      lentiviruses related to BIV, such as Equine Infectious Anemia Virus (EIAV) and
      Human Immunodeficiency Virus (HIV). Analysis of the deletion clones, using the
      bovine immune sera panel, enabled us to identify at least one major epitope which
      was specifically recognized by all bovine sera examined. The ease of expression,
      purification, and specificity of these fusion proteins should enable a thorough
      study of the epidemiology of BIV infection.

PMID- 1372614
TI  - Phospholipid binding of antiphospholipid antibodies and placental anticoagulant
      protein.
AB  - We evaluated the interaction of antiphospholipid antibodies (aPL) with placental
      anticoagulant protein I (PAP I), a calcium-dependent phospholipid binding protein
      which may act as a natural anticoagulant. Clotting assays showed additive
      prolongation of clotting times with aPL and PAP I. ELISA and vesicle phospholipid
      binding studies showed PAP I inhibition of aPL binding to phospholipid but no
      inhibition of PAP I-phospholipid binding by aPL. aPL and PAP I interact
      additively in anticoagulant activity in in vitro clotting systems and compete for
      phospholipid in ELISA system. These data support the hypotheses that aPL and PAP
      I may recognize similar phospholipid epitopes and that in vivo interaction may
      occur.

PMID- 1372615
TI  - Effect of swim-up, Percoll and Sephadex sperm separation methods on the hypo
      osmotic swelling test.
AB  - The separation of spermatozoa from the seminal plasma is required to prepare the
      spermatozoa for intrauterine insemination, in-vitro fertilization and sex
      selection. This study evaluated the effects of sperm preparation techniques on
      the functional integrity of the sperm membrane, as measured by the hypo-osmotic
      swelling test (HOS). Thirty-four semen specimens obtained from the male partner
      of infertile couples were evaluated. A semen analysis and HOS test were performed
      on each specimen. The remainder of the specimen was divided into three equal
      aliquots, the first prepared using Percoll, the second using a swim-up method and
      the third using a Sephadex column. After the preparation, a semen analysis and
      HOS test was performed on each aliquot. The mean and standard deviation for the
      HOS test was 72.9 +/- 8.5% initially, 71.2 +/- 13.1 after Percoll, 75.2 +/- 15.1
      after swim-up and 62.4 +/- 14.5 after Sephadex. Analysis of variance showed that
      the mean HOS score was the same after Percoll and swim-up as it was initially but
      significantly lower after preparation with Sephadex. There was also a higher
      proportion of abnormal semen specimens (HOS less than 50%) after preparation with
      Sephadex than after the other preparation methods. We recommend the use of the
      HOS test as part of a screening panel for sperm separation.

PMID- 1372616
TI  - Rapid detection of respiratory viruses by shell vial culture and direct staining
      by using pooled and individual monoclonal antibodies.
AB  - The Bartels respiratory virus panel detection kit is an indirect fluorescent
      antibody (IFA) method that uses pooled and individual antisera for tissue culture
      confirmation of seven respiratory viruses. We evaluated these reagents for
      detecting viral antigen in shell vial cultures and by direct staining of cells
      from respiratory specimens. The isolation from 254 specimens of respiratory
      viruses in shell vial cultures compared with standard tube cultures was highly
      sensitive (94%) and specific (97.3%). The numbers of viral isolates detected in
      three consecutive years of testing with shell vial cultures were 68 of 254
      (26.8%), 101 of 381 (26.5%), and 122 of 430 (28.4%). IFA direct staining of all
      1,065 specimens resulted in 183 (17.2) being uninterpretable because of
      inadequate numbers of cells or interfering fluorescence. The sensitivity and
      specificity of the interpretable IFA direct stains in comparison with shell vial
      cultures were 85.9 and 87.1%, respectively. For detection of 881 adequate
      specimens, Bartels respiratory syncytial virus IFA direct staining compared with
      an Ortho Diagnostics Systems direct fluorescent-antibody test for respiratory
      syncytial virus RSV was highly sensitive (95.5%) and specific (97%). Shell vial
      cultures combined with Bartels IFA reagents are a rapid alternative to standard
      tube cultures. Bartels IFA direct staining with individual antisera provides
      useful same-day screening of respiratory specimens, but the antiserum pool was
      not effective in screening for positive specimens because of excessive amounts of
      nonspecific fluorescence.

PMID- 1372617
TI  - Rapid detection and typing of dengue viruses from clinical samples by using
      reverse transcriptase-polymerase chain reaction.
AB  - We report on the development and application of a rapid assay for detecting and
      typing dengue viruses. Oligonucleotide consensus primers were designed to anneal
      to any of the four dengue virus types and amplify a 511-bp product in a reverse
      transcriptase-polymerase chain reaction (PCR). First, we produced a cDNA copy of
      a portion of the viral genome in a reverse transcriptase reaction in the presence
      of primer D2 and then carried out a standard PCR (35 cycles of heat denaturation,
      annealing, and primer extension) with the addition of primer D1. The resulting
      double-stranded DNA product of the RT-PCR was typed by two methods: dot blot
      hybridization of the 511-bp amplified product to dengue virus type-specific
      probes or a second round of PCR amplification (nested PCR) with type-specific
      primers, yielding DNA products the unique sizes of which were diagnostic for each
      dengue virus serotype. The accumulated data demonstrated that dengue viruses can
      be accurately detected and typed from viremic human serum samples.

PMID- 1372618
TI  - Serological markers of posttransfusion hepatitis C viral infection.
AB  - Serological markers for hepatitis C virus (HCV) infection were measured in serial
      samples from 14 posttransfusion chronic non-A, non-B hepatitis patients by a
      semiquantitative dot blot immunoassay. The assay detected antibodies to HCV by
      use of recombinant proteins that represent putative HCV capsid (core),
      nonstructural protein 3 (NS3) (33c), and NS4 (c100) epitopes. Seroconversion to
      anti-HCV antibodies (anti-HCV) was detected in all patients. The average time to
      active antibody production detected by any of the recombinant proteins was 13.8
      (range, 3.6 to 22.0) weeks posttransfusion or 4.6 (range, -4.5 to 13.4) weeks
      after the first biochemical marker of illness. Anti-HCV were detected earliest by
      the core antigen in most cases; however, the patterns of anti-HCV responses
      varied significantly among individuals. Overall, the addition of the core and NS3
      antigens to the assay enabled the detection of the antibody response 4 to 5 weeks
      earlier than did the addition of the c100 antigen, the sole antigen used in
      current screening tests in the United States. Passively transferred antibodies
      were detected by at least one antigen in early posttransfusion samples from 12
      patients and decayed below detectable levels for all antigens in only 2 patients.
      Antibodies to all three gene products were evident in the last sample from all
      five patients monitored for greater than 3 years from transfusion indicating the
      persistence of antibodies in patients with chronic illness. Our data show that
      the period following the onset of hepatitis during which anti-HCV are not
      detected by current screening assays can be greatly shortened by the detection of
      anti-HCV responses by a combination of core, NS3, and c100 antigens.

PMID- 1372619
TI  - Detection of herpes simplex virus by a nonradiometric spin-amplified in situ
      hybridization assay.
AB  - An in situ hybridization kit (Diagnostic Hybrids, Inc., Athens, Ohio) was
      evaluated for use in the detection and identification of herpes simplex virus
      (HSV) from clinical specimens. For in situ hybridization, a 10-min spin
      amplification onto monolayers of African green monkey kidney cells (CV-1) in 24
      well polystyrene dishes, 24-h culture amplification, and hybridization with an
      alkaline phosphatase-labeled DNA probe were used. A total of 648 specimens were
      tested, including 275 specimens from patients with symptomatic diseases sent
      specifically for HSV detection and 373 specimens from asymptomatic
      immunocompromised patients sent for detection of HSV shedding. Overall, the
      sensitivity of the hybridization assay was 97.8% (131 of 134 specimens), with 105
      of 105 (100%) specimens from symptomatic patients and 26 of 29 (89.9%) specimens
      from asymptomatic patients being detected. The three specimens that were false
      negative by in situ hybridization had low virus titers, as determined by tissue
      culture. The specificity was 99.6% (512 of 514 specimens). The rapid, accurate
      results suggest that the in situ hybridization kit may be used as an alternative
      to conventional tissue culture for the detection of HSV.

PMID- 1372620
TI  - Species-specific identification of and distinction between Borrelia burgdorferi
      genomic groups by using 16S rRNA-directed oligonucleotide probes.
AB  - Examination of a number of previously published aligned Borrelia 16S rRNA
      sequences revealed the presence of regions which could serve as oligonucleotide
      probe targets for both species-specific identification of Borrelia burgdorferi
      and distinction between genomic groups. Total cellular RNA isolated from Borrelia
      cultures was used in slot blot analysis. Radiolabeled oligonucleotides designed
      to hybridize to specific 16S rRNA targets were used as probes. These probes
      allowed for both species-specific identification and genomic group typing of B.
      burgdorferi.

PMID- 1372621
TI  - High levels of Gardnerella vaginalis detected with an oligonucleotide probe
      combined with elevated pH as a diagnostic indicator of bacterial vaginosis.
AB  - We have demonstrated a new approach to diagnosing bacterial vaginosis (BV) that
      is based on measuring the concentration of Gardnerella vaginalis in vaginal fluid
      with DNA probes. G. vaginalis is virtually always present at high concentrations
      in women who have BV but is also detected frequently in normal women, usually at
      concentrations of less than 10(7) CFU/ml of vaginal fluid. Elevated vaginal pH is
      another sensitive indicator of BV, although it can occur in conjunction with
      other conditions. We have proposed that quantitative measurements of G. vaginalis
      using specific DNA probes can serve as a useful aid in diagnosing BV, provided
      the vaginal pH is above 4.5. To test this hypothesis, a group of 113 women were
      first evaluated for BV by the standard set of clinical signs. Vaginal washes were
      collected, and aliquots were analyzed by quantitative culture for the
      concentration of G. vaginalis. Portions of these same samples were immobilized on
      nylon filters, along with standards for quantitation. The filters were incubated
      with a radiolabelled oligonucleotide specific for G. vaginalis 16S rRNA, and the
      subsequent autoradiographs were examined to determine levels of G. vaginalis in
      each sample. G. vaginalis at concentrations of greater than or equal to 2 x 10(7)
      CFU/ml and vaginal pH of greater than 4.5 were then analyzed for concurrence with
      the diagnoses based on clinical criteria. Results of this slot blot analysis gave
      a sensitivity of 95%, correctly categorizing 41 of 43 BV-positive specimens, and
      a specificity of 99%, correctly identifying 69 of 70 BV-negative specimens,
      compared with diagnosis based on clinical criteria.

PMID- 1372622
TI  - Comparisons of rotavirus VP7-typing monoclonal antibodies by competition binding
      assay.
AB  - Three sets of neutralizing monoclonal antibodies (MAbs) used to type the outer
      capsid protein VP7 of four group A rotavirus serotypes (1 through 4) were
      compared in competition immunoassays. Reciprocal competition was observed for
      each of the VP7 type 2-, 3-, and 4-specific MAbs. The VP7 type 1 MAbs exhibited
      variable competition patterns with other VP7 type 1 MAbs. MAb RV4:3, which has
      been used to recognize antigenic variants within VP7 type 1 strains, showed
      reciprocal competition with the four VP7 type 3 MAbs (RV3:1, YO-1E2, 4F8, and
      159) using a VP7 type 3 virus (SA11) as antigen. MAb 2C9, also prepared against
      VP7 type 1, reacted with VP7 type 3 strains and competed with a VP7 type 3 MAb,
      159, using RRV as antigen. Use of the different sets of VP7 type-specific MAbs in
      the enzyme-linked immunosorbent assay permitted the recognition of six antigenic
      variants within VP7 types 1, 2, and 3 among specimens whose VP7 type could not be
      determined previously with only one set of typing MAbs. These results demonstrate
      differences of typing ability among these VP7-specific MAbs and emphasize the
      need to improve the sensitivity of typing systems by incorporating panels of MAbs
      reacting with several neutralizing epitopes.

PMID- 1372623
TI  - Cellufluor staining of bronchoalveolar lavage samples.

PMID- 1372624
TI  - Intralesional bleomycin and Raynaud's phenomenon.

PMID- 1372627
TI  - Developmental manual dyspraxia: a lesson in mind and brain.
AB  - For decades, pediatricians assiduously documented "soft neurologic signs" in
      children referred for school learning difficulties, although pediatric
      neurologists, including Charles F. Barlow, pointed out the dissociation between
      most neuropsychological abnormalities and the motor findings in question. Later,
      large epidemiologic studies confirmed the independence of soft signs from other
      neuropsychological defects. We used a standardized dyspraxia battery to study 164
      schoolchildren 5 to 12 years old. We found that in the group as a whole there was
      a positive correlation between motor performance in the dyspraxia battery and IQ
      on the Wechsler Intelligence Scale for Children--revised (Full-Scale, Verbal, and
      Performance). In terms of dyspraxia subscales, we found that Performance IQ and
      Full-Scale IQ correlated with imitation of nonsense gestures and use of actual
      objects, whereas Verbal IQ correlated positively only with pantomime on command.
      In contrast, for the group of 24 subjects whose scores on the battery designated
      them as dyspraxic, there was no correlation between dyspraxia scores and IQ.
      Together with the existence of specific, dramatically different, types of
      dyspraxia among the 24 dyspraxic subjects, present findings uphold the earlier
      neurologic opinion that "motor soft signs" are not evidence for fixed "brain
      damage" or even for other types of motor dysfunction, and that dissociation of
      different specific cognitive dysfunctions is the rule within individual patients.

PMID- 1372628
TI  - Early and late replicative chromosomal banding patterns of Gallus domesticus.
AB  - Early and late replicating chromosomal banding patterns of Gallus domesticus were
      investigated by cell synchronization and incorporation of 5'-bromodeoxyuridine
      during early and late DNA synthesis. The early replicating chromosomal banding
      patterns observed, as revealed by either acridine orange or Hoechst
      33258/propidium iodide staining, were similar to the structural G-banding
      patterns obtained by trypsin digestion and Giemsa staining. Late replicating
      chromosomal banding showed extensive reverse band complementarity to the G
      banding pattern. Cell synchronization increased the number of prometaphase and
      metaphase plates available for analysis. G-banding obtained by Hoechst
      33258/propidium iodide staining was investigated due to the fact that it is
      compatible with chromosomal in situ hybridization procedures that use
      nonisotopically-labeled DNA probes. Standard replicative G-banded and R-banded
      idiograms, as obtained after cell synchronization, are proposed.

PMID- 1372626
TI  - Fluent aphasia in children: definition and natural history.
AB  - We compared the course of a preschool child we followed for 4 years with
      published reports of 24 children with fluent aphasia. Our patient spoke fluently
      within 3 weeks of the injury. She was severely anomic and made many semantic
      paraphasic errors. Unlike other children with fluent aphasia, her prosody of
      speech was impaired initially, and her spontaneous language was dominated by
      stock phrases. Residual deficits include chronic impairment of auditory
      comprehension, repetition, and word retrieval. She has more disfluencies in
      spontaneous speech 4 years after her head injury than acutely. School achievement
      in reading and mathematics remains below age level. Attention to the timing of
      recovery of fluent speech and to the characteristics of receptive and expressive
      language over time will permit more accurate description of fluent aphasia in
      childhood.

PMID- 1372625
TI  - Pharmacokinetics and fibrin specificity of alteplase during accelerated infusions
      in acute myocardial infarction.
AB  - Pharmacokinetics and fibrin specificity of alteplase (recombinant tissue-type
      plasminogen activator) were determined in 10 patients with acute myocardial
      infarction undergoing an accelerated infusion regimen during the
      alteplase/anistreplase patency study (TAPS). Fifteen milligrams of alteplase was
      administered as an intravenous bolus injection, followed by infusions of 50 mg
      over 30 min and 35 mg over a further 60 min. Mean steady state plasma
      concentrations of alteplase during the initial 30 min were 3.2 +/- 0.84
      micrograms/ml, measured immunochemically, and 2.1 +/- 0.23 micrograms/ml,
      measured using a functional activity assay. These values were 45% and 51% higher,
      respectively, than those during the standard infusion schedule (p less than
      0.01). However, the predominant plasma half-life determined by model fitting
      based on either assay (3.3 to 3.5 min) was unaltered compared with the standard
      regimen. Maximal concentrations of fibrin and fibrinogen degradation products
      were 5.1 +/- 2.2 and 1.9 +/- 1.1 micrograms/ml, respectively. Plasminogen
      decreased to 70% and alpha 2-antiplasmin to 35% of values before infusion. The
      results indicate that 1) improved coronary patency rates during "front-loaded"
      infusions can be rationalized in terms of higher plasma concentrations of both
      free and immunoreactive alteplase, 2) kinetic variables are comparable with those
      of other dosing strategies, and 3) fibrin specificity is not diminished relative
      to that of the standard infusion regimen.

PMID- 1372629
TI  - Immunolocation analysis of glycosaminoglycans in the human growth plate.
AB  - Monoclonal antibodies were used in this study to immunolocate glycosaminoglycans
      throughout the human growth plate. Chondroitin-4-sulfate, chondroitin-6-sulfate,
      and keratan sulfate were observed in the extracellular matrix of all zones of the
      growth plate and persisted into the cartilage trabeculae of newly formed
      metaphyseal bone. Also present in the extracellular matrix was an oversulfated
      chondroitin/dermatan sulfate glycosaminoglycan which appeared to be specific to
      the proliferative and hypertrophic zones of the growth plate. As with the other
      extracellular matrix molecules, this epitope persisted into the cartilage
      trabeculae of the metaphyseal bone. Zonal differences between the extracellular
      and pericellular or lacunae matrix were also observed. The hypertrophic
      chondrocytes appeared to synthesize chondroitin sulfate chains containing a non
      reducing terminal 6-sulfated disaccharide, which were located in areas
      immediately adjacent to the cells. This epitope was not found to any significant
      extent in the other zones. The pericellular region around hypertrophic
      chondrocytes also contained a keratan sulfate epitope which was also observed in
      the resting zone but not in the proliferative zone. These cell-associated
      glycosaminoglycans were not found in the cartilage trabeculae of metaphyseal
      bone, indicating their removal as the terminal hypertrophic chondrocytes and
      their lacunae are removed by invading blood vessels. These changes in matrix
      glycosaminoglycan content, both in the different zones and within zones, indicate
      constant subtle alterations in chondrocyte metabolic products as they proceed
      through their life cycle of proliferation, maturation, and hypertrophy.

PMID- 1372632
TI  - UV lasers for flow cytometric analysis: HeCd versus argon laser excitation.
AB  - Applying flow cytometric single cell analysis, we compared the performance of UV
      excitation from argon ion and HeCd lasers using various UV-excitable
      fluorochromes of cell kinetic and cell physiological relevance. The AT-specific
      DNA fluorochromes DAPI, Hoechst 33258, and Hoechst 33342 showed no significant
      differences of G1-phase resolution and cell cycle distribution. With the HeCd
      laser, high-resolution cell kinetic analysis applying the novel BrdU/Hoechst-PI
      quenching technique showed superior resolution and an almost normalized G2M/G1
      channel ratio of the first cell cycle. Indo-1 analysis for detection of
      intracellular free calcium gave similar results for both excitation sources,
      although the indo-1 ratio of activated cells was lower for HeCd excitation.
      Monochlorobimane as an indicator fluorochrome of glutathione content could not be
      excited sufficiently with the 325-nm line of the HeCd laser and exhibited poor
      resolution between positive and negative cells. However, the second glutathione
      specific fluorochrome o-phtalaldehyde gave even better results with the HeCd
      laser. Our data indicate that air-cooled HeCd lasers are cheap and reliable UV
      excitation sources for most UV-excitable fluorochromes, and might be an
      alternative to the expensive water-cooled argon and krypton laser.

PMID- 1372631
TI  - Microwave-aided binding of gold-protein-ligand (GPL) complexes. Light microscopic
      observations in the rat brain.
AB  - We describe a rapid method for the preparation and binding site labeling of
      cryostat sections for use in light microscopy. Instead of using antibodies to
      bind to specific sites, substance P, delta-sleep-inducing peptide, oxytocin, and
      dopamine were covalently attached to BSA and then the BSA-ligand complex was
      adsorbed on 5-nm colloidal gold particles. Bioassays carried out on isolated
      organs indicated that the physiological activity of the ligand GPL complex was
      maintained. Most of the technical steps included use of an ordinary microwave
      oven (MWO), with tissues exposed for less than 1 min in any given step. Cryostat
      sections of unfixed rat brain were pre-incubated for 50 sec in the MWO in a Tris
      buffered solution (pH 7.4) containing 1.5% BSA, then further incubated for 50 sec
      in the MWO in Tris-buffered solution containing 1% gelatin and the diluted
      colloidal gold suspension. After washing, the preparations were postfixed for 30
      sec in the MWO in 5% formaldehyde solution, pH 7.4. Finally, the cell-bound gold
      particles were enlarged by a silver-enhancing process and counterstained.
      Preparations observed at high magnification provided excellent resolution of the
      cell binding sites. Positive and negative controls performed by addition of BSA
      conjugated ligands to the pre-incubation and incubation medium, and displacement
      of the markers by an excess of unbound ligand in the pre-incubation or the
      incubation medium, showed the specificity of the tissue labeling.

PMID- 1372630
TI  - S-antigen in rods and cones of the primate retina: different labeling patterns
      are revealed with antibodies directed against specific domains in the molecule.
AB  - S-antigen (arrestin) is a soluble 48 KD protein of the retinal photoreceptor
      cells. It has been found to have a function in regulation of the
      phototransduction cascade. Previous labeling experiments with anti-S-antigen
      (SAg) antibodies have yielded conflicting reports as to the presence of SAg in
      cone photoreceptor cells. In the present study we employed five monoclonal anti
      SAg antibodies (MAb) directed against different known domains in the SAg
      molecule. MAb A9C6, D9F2, and C10C10 are directed against sequences in the
      carboxy half of the SAg molecule. MAb 5C6.47 and F4C1 are directed against the
      amino terminal. Immunoelectron microscopy was used in the localization of SAg in
      LR Gold-embedded baboon retinas. Green/red and blue cones were identified with
      MAb COS-1 and OS-2, respectively. MAb A9C6, D9F2, and C10C10 densely labeled rods
      and blue cones but not green/red cones. MAb 5C6.47 and F4C1 labeled rods and both
      blue and green/red cones. It appears that, in the baboon retina, different SAg
      molecules are present in the blue and green/red cones. Whereas the blue cone SAg
      shares common antigenic determinants with rods, both in the amino and carboxy
      terminals, the green/red cone SAg contains different antigenic determinants at
      the carboxy half of the molecule.

PMID- 1372633
TI  - Binding of an iodinated substance P analogue to cultured anterior pituitary
      prolactin- and luteinizing hormone-containing cells.
AB  - Several lines of anatomic, biochemical, and pharmacological evidence suggest that
      the neuropeptide substance P has a direct action on cells of the anterior
      pituitary lobe via a specific neurokinin-1 receptor. In the present study we
      confirmed this association by combining Bolton-Hunter iodinated substance P
      receptor autoradiography with immunocytochemistry on cultured anterior pituitary
      cells. Radiolabeled substance P was bound to living cell cultures at 0 degrees C,
      and after a brief wash the cultures were fixed and processed immunocytochemically
      for prolactin and luteinizing hormone. A large proportion of cultured anterior
      pituitary cells possessed substance P binding sites. When receptor
      autoradiography was combined with immunocytochemistry, it was evident that both
      prolactin- and luteinizing hormone-immunoreactive cells were labeled with
      radiolabeled substance P. However, a small proportion of the radioligand-labeled
      cells were not stained by the immunocytochemical procedure, suggesting that
      additional cell types possess substance P receptors. The present study presents
      morphological evidence that substance P binds to prolactin- and luteinizing
      hormone-containing cells of the anterior pituitary lobe. Therefore, it is likely
      that substance P has a direct action on mammotrophs and gonadotrophs.

PMID- 1372634
TI  - Lectin staining of cultured CNS microglia.
AB  - Carbohydrate binding proteins, known as lectins, bind to specific sugar groups on
      most membranes. We used fluorescent and light microscopy to study the interaction
      of various lectins with the membranes of microglia cultured from neonatal rat or
      fetal mouse cerebral cortices. Microglia stained intensely with GS-1, RCA, WGA,
      and ConA and slightly with DBA, UEA, BPA, and SBA. No staining was seen with GS
      2, MPA, or PNA. Staining was specific for microglia in the mixed glial cultures
      and was dose dependent. In addition, microglial lectin binding could be reduced
      or blocked by competitive inhibition using specific sugars. Treatment of the
      microglia with agents such as dimethylsulfoxide (DMSO), interleukin-1 (IL-1),
      interferon (IFN), or lipopolysaccharide (LPS) did not eliminate lectin staining,
      although the degree of staining was altered. Positive staining of the microglia
      was also associated with a functional change for at least one lectin, i.e., ConA.
      Superoxide anion production by microglia was increased in the presence of ConA.
      Overall, binding of the lectins GS-1, RCA, WGA, and ConA can be used as an
      identifying tool for microglia in glial cultures, but intensity of staining
      varies depending on their functional state.

PMID- 1372635
TI  - Characterization of antigenic determinants of Borrelia burgdorferi shared by
      other bacteria.
AB  - Three antigenic determinants of Borrelia burgdorferi that were shared with other
      spirochetes and gram-negative bacterial species, as measured by Western blot,
      ELISA, or both, were identified and characterized using monoclonal antibodies
      (MAbs). Two were associated with immunogenic integral membrane lipoproteins of 19
      and 22-kDa, respectively, by [3H]palmitate incorporation and Triton X-114 phase
      partitioning. A third antigenic determinant was shown to be associated with a 72
      kDa heat shock protein that was also immunogenic in human patients. MAb
      agglutination assays with B. burgdorferi and treatment of the spirochete with
      proteases indicated that none of the antigenic determinants were surface exposed.
      NH2-terminal sequence analysis revealed the 72-kDa protein to have 100% identity
      with the first 13 amino acid residues of the Escherichia coli dnaK heat shock
      protein. The presence of these and other shared antigenic determinants in ELISA
      antigen preparations could explain the high degree of serologic cross-reactivity
      in current diagnostic procedures.

PMID- 1372636
TI  - Effect of endotoxin on serum granulocyte and granulocyte-macrophage colony
      stimulating factor levels in dogs.
AB  - The biologic effects of endotoxin are attributed to the release of several
      cytokines, including interleukin-1, interleukin-6, tumor necrosis factor, and the
      colony-stimulating factors. To investigate the mechanism of endotoxin-induced
      neutrophilia in dogs, several cell lines known to proliferate selectively in
      response to recombinant human colony-stimulating factors were examined to
      determine their responses to recombinant canine granulocyte colony-stimulating
      factor (rcG-CSF) or recombinant canine granulocyte-macrophage colony-stimulating
      factor (rcGM-CSF). The murine cell line NFS-60 was found to respond well to rcG
      CSF and the human cell line TALL-101 to rcGM-CSF, and these responses were
      neutralized by antibodies to these recombinant proteins. These bioassays were
      then used to determine G-CSF and GM-CSF levels in dogs after intravenous
      endotoxin administration. G-CSF levels increased by 2 h, peaked at 4 h, and had
      not returned to normal by 24 h after endotoxin. In contrast, GM-CSF was not
      detectible before or after endotoxin administration.

PMID- 1372637
TI  - Pristanic acid and phytanic acid in plasma from patients with peroxisomal
      disorders: stable isotope dilution analysis with electron capture negative ion
      mass fragmentography.
AB  - A sensitive and selective stable isotope dilution method was developed for the
      accurate quantitation of pristanic acid and phytanic acid using electron capture
      negative ion mass fragmentography on pentafluorobenzyl derivatives. This
      technique allows detection of 1 pg of each compound and was applied to plasma
      from healthy controls and patients suffering from various peroxisomal disorders.
      The age-dependency of phytanic and pristanic acid levels in plasma from healthy
      controls was demonstrated. The involvement of peroxisomes in the beta-oxidation
      of pristanic acid was concluded from its accumulation in plasma from patients
      with peroxisomal deficiencies. Pristanic acid/phytanic acid ratios were markedly
      increased in bifunctional protein and/or 3-oxoacyl-CoA thiolase deficiency,
      indicating their role in the (differential) diagnosis of disorders of peroxisomal
      beta-oxidation.

PMID- 1372638
TI  - The ECG and the single channel.
AB  - Our ability to understand and use the ECG has increased with the availability of
      tools to study the heart's electrical system. Great advances were achieved with
      direct electrical recordings from intact animal and human hearts. The
      microelectrode opened the way to recording of the cellular action potentials and
      their underlying currents. We now have two new and powerful methods to study
      cardiac electrophysiology--the patch clamp and molecular biology. We have begun
      to characterize the behavior of the elementary unit of membrane current, the
      single channel. The single channel can best be visualized as existing in a finite
      set of states related sequentially as in a Markov chain. The primary structures
      of several channels have now been determined by cloning, and the structural
      determinants of channel function can be explored. We have entered the molecular
      age of electrophysiology and can expect a greater understanding of the basic
      physiological and pathophysiological processes underlying the ECG. We can also
      expect powerful drugs to be designed based on the structures of their channel
      targets. The ECG remains a rich area for study and an ever better clinical tool.

PMID- 1372639
TI  - The ionic basis of the receptor potential of frog taste cells induced by sugar
      stimuli.
AB  - The ionic mechanism underlying the receptor potential in frog taste cells induced
      by sugar stimuli was studied with conventional microelectrodes by replacing the
      superficial and interstitial fluids of the tongue with modified solutions. The
      taste cell generated a depolarizing receptor potential accompanying a remarkable
      reduction of input resistance in response to stimulation with galactose and
      sucrose. The magnitude of the receptor potential in response to galactose
      solution increased linearly with decreasing pH in the pH range 6-8, but remained
      constant above pH8. The reversal potential was increased by only 29 mV by a 10
      fold increase in the H+ concentration of the stimulus, suggesting that there are
      pH-dependent and pH-independent components in the mechanism generating the
      receptor potential. The use of Na(+)-free, Ca(2+)-free and K(+)-free interstitial
      fluids did not affect the receptor potential, but the elimination of Cl- from the
      interstitial fluid largely abolished it. Interstitial 0.1 mmol l-1 N,N'
      dicyclohexyl-carbodiimide (DCCD) completely inhibited the receptor potential and
      interstitial 0.1 mmol l-1 N-ethylmaleimide (NEM) decreased the potential to 40%
      of the control value. Lowering the pH of interstitial fluid from 7.2 to 6.3
      decreased the receptor potential to 30% of the control value. It is concluded
      that part of the receptor potential in frog taste cells induced by sugar stimuli
      may be produced by an inflow of H+ through the taste-receptive membrane. The
      intracellular pH of the taste cell may be regulated by a Cl(-)-dependent H+ pump
      in the basolateral membrane.

PMID- 1372640
TI  - Differential expression of secretory granule proteases in mouse mast cells
      exposed to interleukin 3 and c-kit ligand.
AB  - It is now established that the subclasses of mast cells (MC) that reside in
      mucosal and serosal environments can be distinguished from one another in terms
      of their expression of specific secretory granule-localized proteases and
      proteoglycans. Further, the hematopoietic- and connective tissue-derived
      cytokines that regulate expression of the genes that encode these constituents of
      the granule can now be identified using recently developed gene-specific probes
      and recombinant cytokines. When bone marrow-derived MC (BMMC) were developed with
      recombinant interleukin 3 (rIL-3) and maintained with this cytokine in the
      absence or presence of recombinant c-kit ligand (rKL), they remained safranin-,
      produced almost no 35S-labeled heparin proteoglycans, and contained greater
      levels of mouse MC protease (MMCP) -5 mRNA and mast cell carboxypeptidase A (MC
      CPA) mRNA than MMCP-6 mRNA. They did not contain MMCP-4 or -2 mRNA, genes
      expressed late in the differentiation of progenitor cells into serosal and
      mucosal MCs, respectively. In contrast, BMMC developed with rKL alone or by
      sequential culture in medium containing rIL-3 followed by rKL expressed high
      levels of MMCP-4 and -6 mRNA, as well as the transcripts that encode MMCP-5 and
      MC-CPA. Although rKL-developed BMMC were safranin+ and produced substantial
      amounts of 35S-labeled heparin proteoglycans, they contained only minimal amounts
      of histamine and MC-CPA enzymatic activity relative to serosal MC. These are the
      first studies to characterize the transcriptional granule phenotype of a
      population of BMMC derived using any recombinant cytokine, to demonstrate a
      dissociation between histochemical staining and granule maturation, and to
      demonstrate antagonistic regulation of late expressed protease genes by a
      cytokine.

PMID- 1372641
TI  - Ligation of VLA-4 on T cells stimulates tyrosine phosphorylation of a 105-kD
      protein.
AB  - The VLA/integrins are a family of heterodimeric adhesion receptors shown to be
      involved in cell-to-cell and cell-to-extracellular matrix (ECM) interactions.
      Given recent evidence that VLA molecules can synergize with the CD3/T cell
      receptor (TCR) pathway to activate T cells, it is important to identify
      biochemical event(s) generated by these molecules. Here, we report that the
      engagement of VLA-4 on T cells with specific antibodies or its ligand activates
      protein-tyrosine kinase (PTK) activity as detected by antiphosphotyrosine
      immunoblotting. The crosslinking of VLA-beta 1 (CD29) with a specific monoclonal
      antibody (mAb) (anti-4B4) plus anti-mouse immunoglobulin resulted in the rapid
      tyrosine phosphorylation of a 105-kD protein (pp105) in the human T cell line H9,
      as well as in peripheral resting T cells. The increase in tyrosine
      phosphorylation of pp105 was specifically mediated by VLA-4, since mAbs against
      alpha 4, but not against other VLA alpha chains, could induce this
      phosphorylation. In addition, the binding of T cells with the CS1 alternatively
      spliced segment of fibronectin (the binding site recognized by VLA-4) induced
      pp105 tyrosine phosphorylation. Crosslinking the CD3 complex or VLA-4 molecules
      with mAbs demonstrated that each of these molecules stimulated the tyrosine
      phosphorylation of unique sets of proteins with different kinetics, suggesting
      that these two receptor systems are coupled to distinct PTKs. Since tyrosine
      phosphorylation of cellular proteins has been shown to be a crucial biochemical
      event in cell growth, our findings suggest that the induction of pp105 tyrosine
      phosphorylation via VLA-4 may play a role in the transduction of activation
      signals through this molecule.

PMID- 1372643
TI  - An acidic fibroblast growth factor protein generated by alternate splicing acts
      like an antagonist.
AB  - Polymerase chain reaction amplification of cDNA for acidic fibroblast growth
      factor in several lines of cultured human cells revealed two forms of mRNA. The
      novel smaller mRNA lacks the entire second coding exon of the acidic fibroblast
      growth factor gene, whereas the previously identified mRNA consists of three
      coding exons. The truncated variant of acidic fibroblast growth factor (aFGF') is
      only 60 amino acids long with an apparent molecular mass of 6.7 kD on sodium
      dodecyl sulfate gels in contrast to 18 kD for the full-length acidic fibroblast
      growth factor. aFGF' elicits only minimal fibroblast proliferation and
      antagonizes the effects of acidic fibroblast growth factor when added exogenously
      to or when coexpressed with aFGF in BALB/c/3T3 fibroblasts. Thus, the truncated
      variant of acidic fibroblast growth factor may provide fibroblasts with a unique
      mechanism for endogenous regulation of their responses to acidic fibroblast
      growth factor.

PMID- 1372642
TI  - Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic
      function and express cytoplasmic CD3 epsilon,delta proteins.
AB  - Natural killer (NK) cells have been defined as CD3 epsilon-, CD16+ and/or CD56+
      lymphocytes that mediate major histocompatibility complex (MHC)-unrestricted
      cytotoxicity against certain tumors and virus-infected cells. Unlike T
      lymphocytes, NK cells do not rearrange or productively express T cell antigen
      receptor genes. Moreover, NK cells from adults have been reported to not express
      CD3 gamma, delta, or epsilon proteins on the cell surface or in the cytoplasm.
      Nonetheless, NK cells have been shown to share a number of antigenic and
      functional similarities to T cells that suggest the possibility of common
      origins. In this report, we demonstrate that functional NK cells exist in liver
      at early stages of human embryonic development. Freshly isolated fetal NK cells
      mediated MHC-unrestricted cytotoxicity against NK-sensitive targets and acquired
      the ability to lyse NK-resistant tumors after overnight culture in interleukin 2.
      Unlike adult NK cells, freshly isolated fetal liver NK cells and clones derived
      from these cells, as well as a subset of cord blood NK cells, express substantial
      levels of CD3 delta and CD3 epsilon proteins in the cytoplasm. Expression of CD3
      epsilon and CD3 delta transcripts and cytoplasmic proteins in fetal NK clones was
      confirmed by polymerase chain reaction and Western blot analysis. These findings
      support the concept that NK and T cells may arise from a common progenitor that
      expresses components of the CD3 complex. Alternatively, it is possible that the
      cytoplasmic CD3 delta, epsilon+ fetal NK cells represent a distinct subpopulation
      of NK cells that is predominant in the fetus, but replaced by the cytoplasmic CD3
      delta,epsilon- adult NK cell population after embryogenesis.

PMID- 1372644
TI  - Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight
      skin mouse interact with similar epitopes.
AB  - We have generated for the first time monoclonal antibodies (mAbs) specific for
      topoisomerase I (topo I) from scleroderma patients, and tight skin mice which
      develop a scleroderma-like syndrome. The epitope specificity of these antibodies
      has been determined using a series of fusion proteins containing contiguous
      portions of topo I polypeptide. Western blot analysis demonstrated that both
      human and mouse mAbs bound strongly to fusion protein C encompassing the NH2
      terminal portion of the enzyme, and weakly to fusion proteins F and G containing
      regions close to the COOH-terminal end of the molecule. This crossreactivity is
      related to a tripeptide sequence homology in F, G, and C fusion proteins. It is
      interesting that a pentapeptide sequence homologous to that in fusion protein C
      was identified in the UL70 protein of cytomegalovirus, suggesting that activation
      of autoreactive B cell clones by molecular mimicry is possible. Both human and
      mouse mAbs exhibiting the same antigen specificity, also share an interspecies
      cross-reactive idiotope. These data suggest that B cell clones producing antitopo
      autoantibodies present in human and mouse repertoire are conserved during
      phylogeny, and are activated during the development of scleroderma disease.

PMID- 1372646
TI  - Characterization of GMP-140 (P-selectin) as a circulating plasma protein.
AB  - GMP-140 is a 140-kD granule membrane protein, found in the alpha granules of
      platelets and the Weibel-Palade bodies of endothelial cells, that is surface
      expressed on cell activation and mediates neutrophil attachment. Cloning data for
      GMP-140 from an endothelial library predict a soluble form of the protein, the
      transcription message for which is also found in platelets. In this study, we
      report the detection by enzyme-linked immunosorbent assay of soluble GMP-140 in
      plasma centrifuged for 3 h at 100,000 g (to remove platelet microparticles) and
      confirm its identity by purification from plasma. Plasma concentrations were
      found to be 0.251 +/- 0.043 micrograms/ml (means +/- SD, n = 10) in normal male
      controls and 0.175 +/- 0.063 micrograms/ml (means +/- SD, n = 10) in normal
      female controls. The purified protein had an identical molecular mass
      (nonreduced) to platelet membrane GMP-140 (approximately 3 kD lower, reduced) and
      was immunoblotted by polyclonal anti-GMP-140, and the anti-GMP-140 monoclonal
      antibodies AK4 and AK6. Analytical gel filtration studies indicated that the
      plasma GMP-140 eluted as a monomer whereas detergent-free, platelet membrane GMP
      140 eluted as a tetramer consistent with plasma GMP-140 lacking a transmembrane
      domain. Purified plasma GMP-140 bound to the same neutrophil receptor as the
      membrane-bound form, and when immobilized on plastic, bound neutrophils
      equivalently to immobilized platelet membrane GMP-140. Since it has been shown
      that fluid-phase GMP-140 is antiinflammatory and downregulates CD18-dependent
      neutrophil adhesion and respiratory burst, its presence in plasma may be of major
      importance in preventing the inadvertent activation of neutrophils in the
      circulation.

PMID- 1372645
TI  - Angiogenesis inhibition suppresses collagen arthritis.
AB  - Neovascularization is observed in a spectrum of diseases such as solid tumors,
      diabetic retinopathy, and rheumatoid arthritis. It is also evident in rat collage
      induced arthritis (CIA), an animal model with histologic, clinical, and
      radiographic manifestations resembling rheumatoid arthritis. To evaluate the
      effects of angioinhibition in CIA, Louvain rats were immunized with type II
      collagen to induce arthritis and then administered an angiogenesis inhibitor, AGM
      1470, in an attempt to either prevent arthritis or suppress established disease.
      Using clinical and radiographic criteria, AGM-1470 prevented CIA and
      significantly suppressed established disease without evidence of
      immunosuppression. Histologic sections from control ankle joints manifested
      pannus and neovascularization, which were absent in experimental animals. This is
      the first study to investigate this novel agent in an autoimmune disease, and
      additional evaluation of this promising compound in other diseases that are
      potentially angiogenesis dependent, such as rheumatoid arthritis, might be
      warranted.

PMID- 1372647
TI  - The in vivo cytotoxic activity of CD8+ T cell clones correlates with their levels
      of expression of adhesion molecules.
AB  - CD8+ T cell clones specific for a defined epitope present in the circumsporozoite
      protein of Plasmodium yoelii display striking differences in their in vivo
      antiplasmodial activity. The adoptive transfer of certain clones (YA23 and YA26)
      into naive mice inhibits by 90% or more the development of liver stages of
      malaria parasites and protects against malaria infection. The adoptive transfer
      of two other T cell clones (YB8 and YA15) results, respectively, in partial or no
      inhibitory activity on parasite development. We found that "protective" and
      "nonprotective" cytotoxic T lymphocyte (CTL) clones do not differ in their fine
      epitope specificity and display similar levels of lysis and DNA degradation of
      target cells in vitro. Their pattern of production of lymphokines and granule
      associated proteins also failed to correlate with their in vivo antiplasmodial
      activity. Histological studies combined with autoradiography showed that, upon
      adoptive transfer, only T cells from the protective CTL clones are capable of
      "associating" with a significant percentage of parasitized hepatocytes.
      Fluorescence-activated cell sorter analysis of surface molecules revealed
      pronounced differences in the levels of CD44 and VLA-4 expression by the
      different clones, correlating closely with their in vivo protective activity. The
      correlation between in vivo antiparasite activity and the expression of CD44 was
      further corroborated by the results of sorting, from the partially protective YB8
      clone, two sub-populations expressing high and low levels of CD44. These were
      protective and nonprotective, respectively. The clones also differed in their
      adhesive properties. Cross-linking of CD44, using specific antibodies, induced
      LFA-1-mediated homotypic aggregation of protective clones, while nonprotective
      cells failed to aggregate.

PMID- 1372648
TI  - Depletion of alpha/beta T cells by a monoclonal antibody against the alpha/beta T
      cell receptor suppresses established adjuvant arthritis, but not established
      collagen-induced arthritis in rats.
AB  - The effects of treatment with a monoclonal antibody (R73 mAb) against T cell
      receptor alpha/beta (TCR-alpha/beta) on both established adjuvant arthritis (EAA)
      and established collagen-induced arthritis (ECIA) in rats have been investigated.
      Rats were treated with R73 mAb when arthritis reached a peak. Treatment with the
      anti-TCR-alpha/beta mAb markedly suppressed EAA, whereas ECIA was not affected by
      the mAb treatment. Histologically, R73 mAb-treated rats with EAA showed mild
      hyperplasia of synovial tissues, sparse infiltration of inflammatory cells, and
      minimal erosion of cartilage, whereas arthritic rats treated with PBS and an
      irrelevant control mAb against Giardia had marked hyperplasia of synovium with
      pannus, massive inflammatory cell infiltrate, and severe destruction of cartilage
      and subchondral bone. R73 mAb-treated rats with ECIA exhibited pronounced
      formation of pannus containing many inflammatory cells and marked cartilage and
      subchondral damage similar to those in arthritic rats that received the control
      treatments. Treatment with R73 mAb depleted markedly alpha/beta+ T cells in both
      peripheral blood and synovial tissues of rats with EAA and ECIA. R73 mAb
      treatment was associated with marked reduction in arthritogen-specific delayed
      type hypersensitivity responses in both EAA and ECIA. The titers of antibodies
      against type II collagen produced in rats with ECIA were not affected by the mAb.
      Thus, alpha/beta+ T cells appear to have a central role in EAA, but not in
      chronic ECIA.

PMID- 1372651
TI  - Excitatory amino acid receptors on isolated retinal ganglion cells from the
      goldfish.
AB  - 1. Whole-cell currents activated by the excitatory amino acids L-glutamic acid
      (glutamate, Glu), L-aspartic acid (Asp), and their analogues N-methyl-D-aspartate
      (NMDA), kainic acid (KA), quisqualic acid (QA), and alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) were recorded from ganglion cells
      enzymatically dissociated from goldfish retina and grown in culture. All agonists
      induced detectable whole-cell responses in the majority of cells cultured from 2
      to 72 h. 2. Currents activated by each of the agonists were selective for cations
      (Na+) over anions (Cl-). The responses to Glu, NMDA, and Asp were each
      potentiated when 1 microM glycine was coapplied. Extracellular Mg2+ blocked
      completely the response to NMDA plus glycine in cells held at negative
      potentials, but the block was relieved when cells were more depolarized. 3. Dose
      response measurements revealed a rank order of sensitivity to the Glu analogues
      in the presence of 1 microM glycine and zero extracellular Mg2+; QA greater than
      AMPA greater than NMDA greater than KA. Cells were not responsive to APB (L-2
      aminophosphonobutyric acid). 4. Kynurenic acid (Ky) produced a noncompetitive
      block of the NMDA response in the presence of 1 microM glycine with a Ki of 40
      microM. Responses to KA, QA, and AMPA were blocked competitively by Ky with Kis
      of 72, 148, and 656 microM, respectively. QA and AMPA competitively blocked the
      response to KA with Kis of 114 microM and 1 mM, respectively. NMDA single
      channels had a mainstate slope conductance of 27-30 pS and two subconductance
      levels of 5 and 24 pS at 13 degrees C in symmetrical Na+. 5. Whole-cell responses
      to QA and AMPA were highly correlated, suggesting that QA and AMPA activated the
      same receptor or class of receptors; whereas, responses to QA and KA were not
      well correlated, suggesting that these agonists at least in part activated
      separate receptor populations.

PMID- 1372650
TI  - Identification of overlapping HLA class I-restricted cytotoxic T cell epitopes in
      a conserved region of the human immunodeficiency virus type 1 envelope
      glycoprotein: definition of minimum epitopes and analysis of the effects of
      sequence variation.
AB  - Although the immunologic basis of protective immunity in human immunodeficiency
      virus type 1 (HIV-1) infection has not yet been defined, virus-specific cytotoxic
      T lymphocytes (CTL) are likely to be an important host defense and may be a
      critical feature of an effective vaccine. These observations, along with the
      inclusion of the HIV-1 envelope in the majority of vaccine candidates presently
      in clinical trials, underscore the importance of the precise characterization of
      the cellular immune responses to this protein. Although humoral immune responses
      to the envelope protein have been extensively characterized, relatively little
      information is available regarding the envelope epitopes recognized by virus
      specific CTL and the effects of sequence variation within these epitopes. Here we
      report the identification of two overlapping CTL epitopes in a highly conserved
      region of the HIV-1 transmembrane envelope protein, gp41, using CTL clones
      derived from two seropositive subjects. An eight-amino acid peptide was defined
      as the minimum epitope recognized by HLA-B8-restricted CTL derived from one
      subject, and in a second subject, an overlapping nine-amino acid peptide was
      identified as the minimal epitope for HLA-B14-restricted CTL clones. Selected
      single amino acid substitutions representing those found in naturally occurring
      HIV-1 isolates resulted in partial to complete loss of recognition of these
      epitopes. These data indicate the presence of a highly conserved region in the
      HIV-1 envelope glycoprotein that is immunogenic for CTL responses. In addition,
      they suggest that natural sequence variation may lead to escape from immune
      detection by HIV-1-specific CTL. Since the region containing these epitopes has
      been previously shown to contain an immunodominant B cell epitope and also
      overlaps with a major histocompatibility complex class II T cell epitope
      recognized by CD4+ CTL from HIV-1 rgp160 vaccine recipients, it may be
      particularly important for HIV-1 vaccine development. Finally, the identification
      of minimal CTL epitopes presented by class I HLA molecules should facilitate the
      definition of allele-specific motifs.

PMID- 1372649
TI  - Antibody and B7/BB1-mediated ligation of the CD28 receptor induces tyrosine
      phosphorylation in human T cells.
AB  - CD28 is an adhesion receptor expressed as a 44-kD dimer on the surface of a major
      subset of human T cells. The CD28 receptor regulates the production of multiple
      lymphokines, including interleukin 2 (IL-2), by activation of a signal
      transduction pathway that is poorly understood. Here we show that ligation of
      CD28 by a monoclonal antibody (mAb) or by a natural ligand, B7/BB1, induces
      protein tyrosine phosphorylation that is distinct from T cell receptor (TCR)
      induced tyrosine phosphorylation. CD28-induced protein tyrosine phosphorylation
      was greatly enhanced in cells that had been preactivated by ligation of the TCR,
      or by pretreatment with phorbol esters. Rapid and prolonged tyrosine
      phosphorylation of a single substrate, pp100, was induced in T cells after
      interaction with B7/BB1 presented on transfected Chinese hamster ovary (CHO)
      cells. Anti-B7 mAb inhibited B7/BB1 receptor-induced tyrosine phosphorylation,
      indicating that B7-CD28 interaction was required. CD28-induced tyrosine
      phosphorylation was independent of the TCR because it occurred in a variant of
      the Jurkat T cell line that does not express the TCR. Herbimycin A, a protein
      tyrosine kinase inhibitor, could prevent CD28-induced tyrosine phosphorylation
      and CD28-induced IL-2 production in normal T cells. The simultaneous crosslinking
      of CD28 and CD45, a tyrosine phosphatase, could prevent tyrosine phosphorylation
      of pp100. These results suggest that specific tyrosine phosphorylation,
      particularly of pp100, occurs directly as a result of CD28 ligand binding and is
      involved in transducing the signal delivered through CD28 by accessory cells that
      express the B7/BB1 receptor. Thus, this particular form of signal transduction
      may be relevant to lymphokine production and, potentially may provide a means to
      study the induction of self-tolerance, given the putative role of the
      costimulatory signal in the induction of T cell activation or anergy.

PMID- 1372654
TI  - Regulation of steroid synthesis and metabolism in isolated binucleate cells of
      the placenta in sheep and goats.
AB  - Binucleate cells of sheep and goat fetal placentae comprise about one-fifth of
      the trophectodermal layer at the feto-maternal interface. When isolated and
      incubated in vitro they produce the steroids that are synthesized by the placenta
      in vivo (progesterone in sheep, 5 beta-pregnane-3 alpha,20 alpha diol in goats).
      This study demonstrates that progesterone synthesis in binucleate cell
      preparations in sheep was increased by prostaglandin (PG) E-2,
      nordihydroguaiaracetic acid (NDGA) and methylisobutylxanthine, but reduced by
      indomethacin, whereas in goats only NDGA produced any effect (an increase). None
      of the other compounds tested (luteinizing hormone, follicle stimulating hormone,
      prolactin, dibutyryl cAMP, A23187 or phorbolmyristic acetate) had any effect.
      Sheep binucleate cells also produced PGE-2 from arachidonic acid. These results
      suggest that, in sheep, products of both the cyclooxygenase (producing PGE-2) and
      lipoxygenase (inhibited by NDGA) pathways of arachidonic acid metabolism have
      regulatory roles in placental steroid synthesis, but only the lipoxygenase
      pathway is relevant in goats.

PMID- 1372653
TI  - Relative proportions of pathogen-related oral spirochetes (PROS) and Treponema
      denticola in supragingival and subgingival plaque from patients with
      periodontitis.
AB  - The purpose of this study was to use monoclonal antibodies to enumerate
      spirochetes in dental plaque, including the newly recognized pathogen-related
      oral spirochete (PROS) and specific serovars of Treponema denticola. Plaque was
      collected from control subjects with no apparent periodontal disease and from
      sites of moderate to severe chronic periodontitis in patients with inflammatory
      periodontal disease. Individual monoclonal antibodies were used to determine
      whether spirochetes were present and then a double-staining protocol was employed
      to count total spirochetes and specific treponemes in individual microscopic
      fields. Results indicate that spirochetes are more common at diseased sites and
      in subgingival plaque than at healthy sites or in supragingival plaque. Together
      PROS and T. denticola comprised the majority of all spirochetes in all samples
      and PROS and T. denticola serovars "B" and D were most numerous in plaque from
      patients with periodontitis. PROS were the majority of all spirochetes in
      supragingival plaque (76.2% +/- 23.8%) and subgingival plaque (60.9% +/- 19.1%)
      from periodontitis patients, significantly larger than the percentage of T.
      denticola serovar "B" (P less than .001 for both supragingival and subgingival
      plaque) and serovar D (P less than .01 for supragingival and P less than .001 for
      subgingival plaque). These observations indicate that PROS are the predominant
      spirochete in plaque from sites of patients with periodontitis, but other
      analytical approaches are necessary to determine if PROS or T. denticola are
      pathogenic.

PMID- 1372655
TI  - NG-allyl- and NG-cyclopropyl-L-arginine: two novel inhibitors of macrophage
      nitric oxide synthase.
AB  - NG-Methyl-L-arginine has recently been shown to inactivate the inducible murine
      macrophage nitric oxide (.NO) synthase (Olken, N. M.; Rusche, K. M.; Richards, M.
      K.; Marletta, M. A. Biochem. Biophys. Res. Commun. 1991, 177, 828-833). NG-Allyl
      L-arginine and NG-cyclopropyl-L-arginine were synthesized as potential mechanism
      based enzyme inhibitors to exploit the chemistry presumed to occur at the active
      site. NG-Cyclopropyl-L-arginine was found to be a potent reversible inhibitor
      with a Ki = 7.7 microM. NG-Allyl-L-arginine was found to be both a potent
      reversible (Ki = 2.1 microM) and irreversible inhibitor of the enzyme. This
      irreversible inhibition demonstrated pseudo-first-order inactivation kinetics
      with kinact = 0.026 min-1 and KI = 3.4 microM. Stereospecific protection of the
      inactivation was afforded by L-arginine, and saturability of the inactivation
      rate was observed. Our studies indicate that both reversible and irreversible
      inhibition of the inducible .NO synthase can be achieved with relatively simple
      modifications of the substrate L-arginine.

PMID- 1372652
TI  - Enhancement of erythropoiesis by recombinant human erythropoietin in low birth
      weight infants: a pilot study.
AB  - We randomly assigned eight concurrently symptom-free premature infants (birth
      weight less than or equal to 1250 gm) at high risk of requiring erythrocyte
      transfusions for anemia of prematurity to 6 weeks of intensive treatment with
      either subcutaneous recombinant human erythropoietin (r-HuEPO group) or a placebo
      (control group). Treatment with r-HuEPO was initiated at a dose of 100 units/kg
      per day 5 days a week, and was increased to 200 units/kg per day after 2 or 3
      weeks if target reticulocyte counts were not achieved. All patients were given
      supplemental oral iron therapy at a dose of 6 mg/kg per day, as tolerated. Mean
      reticulocyte counts in r-HuEPO-treated and control infants were 64,600 versus
      67,500 cells/mm3 at entry; were 245,600 versus 78,000 cells/mm3 after 1 week; and
      averaged 262,600 versus 136,400 cells/mm3 during the study. Mean reticulocyte
      counts in r-HuEPO-treated infants were 251,200 cells/mm3 during the week when r
      HuEPO, 100 units/kg per day, was given, and were 269,500 cells/mm3 after the dose
      was increased to 200 units/kg per day. Mean hematocrit values at entry were 33.4%
      in babies who received r-HuEPO versus 33.6% in the control subjects, and were
      31.4% in r-HuEPO-treated and 25.2% in the control subjects at the end of
      treatment. One r-HuEPO-treated and three control babies received transfusions
      during the study; the total volume of blood given was 17 ml in the r-HuEPO group
      and 101 ml in the control subjects. The percentage of hemoglobin F increased in
      infants not given transfusions. We conclude that r-HuEPO stimulates endogenous
      erythropoiesis in small premature babies who are receiving supplemental oral iron
      therapy. A controlled multicenter trial has been undertaken to confirm these
      promising preliminary observations.

PMID- 1372658
TI  - Spermatic cord beta-human chorionic gonadotropin levels in seminoma and their
      clinical implications.
AB  - Current opinions differ as to the biological significance and treatment of pure
      seminoma associated with the serological establishment of beta-human chorionic
      gonadotropin. Between December 1987 and April 1990, 147 patients with malignant
      testicular tumors were treated. Of these patients 47 (32%) had a pure seminoma.
      In 35 of the 47 patients we measured the tumor markers beta-human chorionic
      gonadotropins and alpha-fetoprotein in the cubital vein blood and testicular vein
      blood. There were elevated beta-human chorionic gonadotropin levels in the
      cubital veins of 26% of the patients, in agreement with the literature. However,
      elevated levels were found in the testicular veins of 80% of the patients, which
      reflects the high sensitivity of marker identification in testicular vein blood.
      Apparently, most seminomas produce beta-human chorionic gonadotropin even if it
      is not detectable in the cubital vein. We believe that the presence of this
      marker in patients with pure seminoma is not an indication of greater tumor
      aggressiveness but of tumor mass.

PMID- 1372657
TI  - Cl- channels in intact human T lymphocytes.
AB  - We recently described a large, multiple-conductance Cl- channel in excised
      patches from normal T lymphocytes. The properties of this channel in excised
      patches are similar to maxi-Cl- channels found in a number of cell types. The
      voltage dependence in excised patches permitted opening only at nonphysiological
      voltages, and channel activity was rarely seen in cell-attached patches. In the
      present study, we show that Cl- channels can be activated in intact cells at
      physiological temperatures and voltages and that channel properties change after
      patch excision. Maxi-Cl- channels were reversibly activated in 69% of cell
      attached patches when the temperature was above 32 degrees C, whereas fewer than
      2% of patches showed activity at room temperature. Upon excision, the same
      patches displayed large, multiple-conductance Cl- channels with characteristics
      like those we previously reported for excised patches. After patch excision, warm
      temperatures were not essential to allow channel activity; 37% (114/308) of
      inside-out patches had active channels at room temperature. The voltage
      dependence of the channels was markedly different in cell-attached recordings
      compared with excised patches. In cell-attached patches, Cl- channels could be
      open at cell resting potentials in the normal range. Channel activation was not
      related to changes in intracellular Ca2+ since neither ionomycin nor mitogens
      activated the channels in cell-attached patches, Ca2+ did not rise in response to
      warming and the Cl- channel was independent of Ca2+ in inside-out patches. Single
      channel currents were blocked by internal or external Zn2+ (100-200 microM), 4
      acetamido-4' isothiocyanostilbene-2,2'-disulfonate (SITS, 100-500 microM) and
      4,4'-diisothiocyanostilbene 2,2'-disulfonate (DIDS, 100 microM). NPPB (5-nitro-2
      (3-phenylpropylamino)-benzoate) reversibly blocked the channels in inside-out
      patches.

PMID- 1372656
TI  - Spatial and temporal patterns of intracellular calcium in colonic smooth muscle.
AB  - Intracellular calcium [Ca2+]i measurements in cell suspension of gastrointestinal
      myocytes have suggested a single [Ca2+]i transient followed by a steady-state
      increase as the characteristic [Ca2+]i response of these cells. In the present
      study, we used digital video imaging techniques in freshly dispersed myocytes
      from the rabbit colon, to characterize the spatiotemporal pattern of the [Ca2+]i
      signal in single cells. The distribution of [Ca2+]i in resting and stimulated
      cells was nonhomogeneous, with gradients of high [Ca2+]i present in the
      subplasmalemmal space and in one cell pole. [Ca2+]i gradients within these
      regions were not constant but showed temporal changes in the form of [Ca2+]i
      oscillations and spatial changes in the form of [Ca2+]i waves. [Ca2+]i
      oscillations in unstimulated cells (n = 60) were independent of extracellular
      [Ca2+] and had a mean frequency of 12.6 +/- 1.1 oscillations per min. The
      baseline [Ca2+]i was 171 +/- 13 nM and the mean oscillation amplitude was 194 +/-
      12 nM. Generation of [Ca2+]i waves was also independent of influx of
      extracellular Ca2+. [Ca2+]i waves originated in one cell pole and were visualized
      as propagation mostly along the subplasmalemmal space or occasionally throughout
      the cytoplasm. The mean velocity was 23 +/- 3 microns per sec (n = 6). Increases
      of [Ca2+]i induced by different agonists were encoded into changes of baseline
      [Ca2+]i and the amplitude of oscillations, but not into their frequency. The
      observed spatiotemporal pattern of [Ca2+]i regulation may be the underlying
      mechanism for slow wave generation and propagation in this tissue. These findings
      are consistent with a [Ca2+]i regulation whereby cell regulators modulate the
      spatiotemporal pattern of intracellularly generated [Ca2+]i oscillations.

PMID- 1372659
TI  - Variability and circadian changes in home uroflowmetry in patients with benign
      prostatic hyperplasia compared to normal controls.
AB  - We evaluated the variability and circadian changes in consecutive measurements of
      home uroflowmetry in 32 patients with symptomatic benign prostatic hyperplasia
      (BPH) and 16 healthy men. In the BPH group 476 uroflow measurements were recorded
      during 24 to 72 hours (mean 14.9 measurements per patient), and the controls
      produced 100 flow recordings (mean 6.25 measurements per participant). Great
      variability between consecutive peak flow rates was observed in the BPH group,
      ranging from at least 1 standard deviation in 28 of 32 patients (87.5%) to at
      least 2 standard deviations in 15 of 32 (47%). In 21 of 32 patients (65.6%) the
      highest recorded peak flow rate was greater than, while the lowest peak flow rate
      was less than the -2 standard deviations plot in voiding nomograms. In the
      control group variability between consecutive voiding episodes also was marked,
      namely at least 1 standard deviation in 8 of 16 men (50.0%) and at least 2
      standard deviations in 2 of 16 (12.5%). However, in none of the control men was
      any peak flow rate measurement less than the -2 standard deviations line.
      Circadian changes in diurnal and nocturnal measurements of voided volume,
      interval to maximal flow, flow time, peak flow rate and adjusted peak flow rate
      were recorded in the BPH group, providing a urodynamic support to a well known
      clinical observation.

PMID- 1372660
TI  - Localized hyperthermia versus the sham procedure in obstructive benign
      hyperplasia of the prostate: a prospective randomized study.
AB  - Hyperthermia was shown to cause improvement in 50 to 60% of the patients with
      benign prostatic hyperplasia (BPH) without considering placebo effects. We
      studied 68 patients randomly assigned to a treatment group (38) and a sham group
      (30) who underwent the same manipulation but without applying radio frequency
      power. The Biodan Prostathermer was used. Criteria for inclusion were based on
      objective and subjective symptoms. Treatment was performed 6 times at 43 +/- 0.5C
      for the treatment group. Followup evaluation was performed at 3 months, and the
      same objective and subjective symptoms were recorded. We observed a statistically
      significant subjective improvement in the sham group (33%) that was not
      accompanied by any significant objective improvement. In the treatment group the
      subjective response was significantly better regarding number of patients (68%)
      and response rate, and was substantiated by a significant improvement in all
      objective symptoms (53% of the patients) except voided volume. Therefore,
      hyperthermia treatment had a definite therapeutic effect on BPH in excess of
      placebo.

PMID- 1372661
TI  - Effect of recombinant human granulocyte colony-stimulating factor in patients
      receiving chemotherapy for urogenital cancer. Urological rhG-CSF Study Group.
AB  - We evaluated the efficacy and safety of recombinant human granulocyte colony
      stimulating factor (G-CSF) in patients with leukopenia after chemotherapy for
      urogenital cancers. Recombinant human G-CSF was administered at 100
      micrograms./m.2 intravenously in 36 patients and at 75 micrograms. per body
      weight subcutaneously in 37 for 8 days after methotrexate, vinblastine,
      doxorubicin and cisplatin (M-VAC) therapy or for 14 days after other
      chemotherapies. Cycle 1 of chemotherapy was given without recombinant human G
      CSF, while at cycle 2, recombinant human G-CSF was given additionally. Therefore,
      cycle 1 of the regimen served as a control to cycle 2 in each patient. An
      elevation in the median white blood cell nadir was noted: 1,500 versus 3,200
      (intravenous) and 2,100 versus 3,200 (subcutaneous) on M-VAC therapy, and 1,800
      versus 2,100 (intravenous) and 1,700 versus 2,500 (subcutaneous) on other
      chemotherapeutic regimens. A shortening of the leukopenic period was observed in
      cycle 2. There were no significant adverse side effects attributed to the use of
      recombinant human G-CSF. The results indicate that recombinant human G-CSF may be
      safely and effectively used against leukopenia after chemotherapy for urogenital
      cancer. This remedy will become useful for completion of the schedule and dose
      intensification of chemotherapy in the future. Subcutaneous administration is
      considered to be the more preferable route.

PMID- 1372662
TI  - Prostate and bone fibroblasts induce human prostate cancer growth in vivo:
      implications for bidirectional tumor-stromal cell interaction in prostate
      carcinoma growth and metastasis.
AB  - Prostate cancer selectively metastasizes to the axial skeleton to produce
      osteoblastic lesions, which suggests that bidirectional paracrine interactions
      exist between prostate cancer and bone cells. To evaluate the role of tumor
      stromal cell interaction and stromal-specific growth factors in prostate cancer
      growth and dissemination, we coinoculated nontumorigenic human prostate cancer
      cells (LNCaP) and various tissue-specific fibroblasts subcutaneously in athymic
      mice. LNCaP tumors were induced most consistently by human bone fibroblasts
      (62%), followed by two prostate fibroblast cell lines (31% and 17%), but not by
      lung, kidney, or embryonic 3T3 fibroblasts. Carcinomas formed preferentially in
      male hosts, demonstrating in vivo androgen sensitivity. Immunohistochemical and
      biochemical techniques confirmed the human prostate component of these tumors and
      were paralleled by elevations in serum prostate specific antigen. In vitro
      mitogenic assays revealed a two-to three-fold bidirectional stimulation between
      LNCaP and bone or prostate fibroblast conditioned media, but not lung, kidney, or
      3T3 fibroblast conditioned media. A novel method developed to deliver
      concentrated bone or prostate fibroblast conditioned media in vivo using a slowly
      absorbed matrix (gelfoam) also induced tumor formation, emphasizing the
      importance of fibroblast growth factors in LNCaP tumor formation. Northern
      analysis identified the stromal compartment as the primary source of
      extracellular matrix (collagen, fibronectin), while only LNCaP cells expressed
      transforming growth factor alpha. Although LNCaP and stromal cells express basic
      fibroblast growth factor (bFGF), the bidirectional paracrine-mediated mitogenic
      activity between these cells is not inhibited by anti-bFGF antibodies, suggesting
      that other undefined growth factors may be involved in stimulating LNCaP growth.
      These observations illustrate the importance of stromal-epithelial interaction in
      prostate tumor growth and suggest that extracellular matrix and paracrine
      mediated growth factors play a role in prostate cancer growth and metastasis.

PMID- 1372663
TI  - Quantifying the smooth muscle content of the prostate using double
      immunoenzymatic staining and color assisted image analysis.
AB  - The primary objective of the present study was to develop a method for
      quantifying the smooth muscle content of the prostate adenoma. A double
      immunoenzymatic staining technique was coupled with color assisted image analysis
      to determine the area density of the smooth muscle within the prostate adenoma.
      Eight males with symptomatic BPH underwent transrectal biopsy of the prostate.
      Four micron thick tissue sections were used for the double immunoenzymatic
      staining process. Rabbit anti-desmin and mouse anti-human prostatic acid
      phosphatase antibodies were used to selectively bind smooth muscle and prostatic
      epithelium, respectively. The two different tissue antigens were identified with
      peroxidase-antiperoxidase (PAP) and alkaline phosphatase-antialkaline phosphatase
      techniques. The alkaline phosphatase activity and peroxidase activity were
      developed with fast red and DAB chromogens. The BQ MEG IV Vista color system
      image analysis was used to discriminate color differences from the stained tissue
      sections. The thresholds were set to identify smooth muscle (dark brown),
      epithelium (red), fibrous tissue (pale brown), and glandular lumina (colorless).
      The mean area density of smooth muscle, fibrous tissue, glandular epithelium, and
      glandular lumina was 22%, 54%, 16%, and 9%, respectively. The present study
      suggests that a significant component of the prostate adenoma is smooth muscle.
      The application of this technique will be utilized to provide further insights
      into the role of smooth muscle in the pathogenesis and therapy of BPH.

PMID- 1372664
TI  - [Influence of normovolemic hemodilution on the respiratory and circulatory
      systems].
AB  - We studied respiratory and circulatory kinetics of normovolemic hemodilution in
      adult mongrel dogs. The dogs were divided into two groups; Dextran-40 (group A)
      and SALIN-HES (group B). No difference in PaO2 and PaCO2 was noted between the
      two groups. MPA and CI during normovolemic hemodilution were higher in group A
      than in group B. However, MPA, Qs/Qt and ETVI during normovolemic hemodilution
      were largely influenced in group A. L/P during normovolemic hemodilution was more
      influenced in group B than in group A. The compensatory effect with increase of
      the cardiac output during normovolemic hemodilution was noted until S3 (Hct =
      10%), but it was not noted at S4 (Hct = 5%) and S5 (just before death). SvO2 is
      the most sensitive index indicating the risk of normovolemic hemodilution.

PMID- 1372665
TI  - [Anesthetic management of palliative surgery for hypoplastic left heart syndrome-
      a case report].
AB  - The first patient with hypoplastic left heart syndrome who was treated
      successfully by palliative surgery at our hospital is reported. Soon after birth,
      the female infant showed tachypnea and cyanosis, and was transferred to our
      institution under a presumptive diagnosis of HLHS. Although cardiologists
      confirmed the diagnosis by two-dimensional echocardiography, the surgery was
      postponed for one month because it was possible to keep the ductus arteriosus
      open without PGE1, and the patient showed no deterioration. Fortunately, an
      abnormal vessel connecting the left atrium with the superior vena cava relieved
      severe pulmonary venous congestion by diverting the blood flow. During the pre
      CPB period, frequent adjustment of the oxygen concentration and ventilator
      setting was required in order to keep the blood gas values optimal compared with
      the values before surgery. After CPB, adequate blood pressure using
      catecholamines and hyperventilation with 100% oxygen was necessary to increase
      the pulmonary blood flow and to decrease the pulmonary vascular resistance. It is
      concluded that preservation of the balance between PVR and SVR during the
      perioperative period, and adequate systemic arterial pressure after CPB are
      crucial. Furthermore, constant and intense observation is mandatory to facilitate
      immediate treatment even after surgery in case of systemic hypoperfusion due to
      excessive pulmonary blood flow.

PMID- 1372666
TI  - [Application of FDA/EB staining for the detection of viable or non-viable
      mycobacteria in clinical specimens].
AB  - Two-hundred sputum specimens from tuberculosis patients were examined for viable
      or non-viable mycobacteria by a combination of fluorescein diacetate ethidium
      bromide (FDA/EB) staining, Ziehl-Neelsen staining, and the use of cultures in 3%
      Ogawa egg medium. The sputum specimens were treated with 3% NaOH for 10 min and
      washed in PBS. The bacteria was then harvested by centrifugation at 6,000 rpm for
      5 min. Each sample was subjected to FDA/EB staining, Ziehl-Neelsen staining and
      cultures to compare the staining -method results and the results of colony
      formation. Ziehl-Neelsen staining method revealed acid-fast bacteria in the
      specimens, distributed from Gaffky 1 to Gaffky 8. The number of FDA-positive
      specimens and culture-positive specimens were identical in all Gaffky grades,
      suggesting that the FDA staining method well reflected the presence of viable
      mycobacteria in the specimens. We concluded that FDA staining is a valuable
      method to detect viable mycobacteria in sputum specimens on the first day of
      examination. It is therefore advantageous for doctors and patients to be
      immediately informed of culture results rather than waiting for several weeks.

PMID- 1372667
TI  - Immunocytochemical localization of proANF 1-30, proANF 31-67 and atrial
      natriuretic factor in the kidney.
AB  - ProANF [1-30 first 30 amino acids (a.a) of the 126 a.a atrial natriuretic factor
      (ANF) prohormone], ProANF 31-67 (a.a 31-67) as well as atrial natriuretic factor
      (a.a 99-126), of the ANF prohormone localized to the sub-brush border of the pars
      convoluta and pars rectus of the proximal tubules of hydrated and dehydrated rat
      kidneys with immunoperoxidase staining. Immunofluorescent studies revealed that
      each of these peptides and especially ProANF 31-67 had a strong predilection for
      the perinuclear region in the proximal and distal tubules. ProANFs 1-30, 31-67,
      and 99-126 (that is, ANF) also localized with both immunoperoxidase and
      immunofluorescent staining to the cortical collecting ducts, glomeruli,
      peritubular, and interstitial blood vessels. ProANF 31-67 immunoperoxidase
      staining was particularly striking in the elastica of the small and large
      interstitial arteries. The whole prohormone being present was suggested by
      immunological recognition in the rat kidney of both the N-terminus and C-terminus
      of the ANF prohormone by radioimmunoassays. The concentration of the N-terminus
      in the kidney was 1.0 +/- 0.03 ng/g of kidney weight, while the C-terminus of the
      ANF prohormone concentration was 0.4 +/- 0.01 ng/g of kidney tissue. These
      findings of a sub-brush border and perinuclear location of the N-terminal and C
      terminal ANF prohormone peptides suggest that the atrial natriuretic factor
      prohormone may be synthesized in and/or the respective peptides are captured by
      the proximal tubules, but also to a lesser extent by the distal tubules of the
      kidney.

PMID- 1372669
TI  - Self-renewal inhibition of acute myeloid leukemia clonogenic cells by biological
      inducers of differentiation.
AB  - We analyzed the maintenance of acute myeloid leukemia clonogenic cells (AML CFU
      L) in liquid culture in the presence of five potential differentiation inducers:
      trans-retinoic acid, 1,25-dihydroxy vitamin D3, interferon gamma, granulocyte
      colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF),
      used singly and with two combined. The culture medium contained either fetal
      bovine or human serum from normal donors. CFU-L recovery after 7 days was
      compared to that observed in control cultures. Of AML cases and HL60 cells, 11/15
      displayed greater than 50% CFU-L reduction in response to one or more inducers.
      In 8/9 responsive cases that underwent the nitroblue tetrazolium (NBT) reduction
      test, an increase in the percentage of functionally mature (NBT-positive) cells
      was detected. The combination of retinoic acid with interferon gamma was most
      effective in reducing CFU-L recovering (8 responsive/15 AML cases), G-CSF and M
      CSF displayed either inhibitory or stimulatory activity in different AML cases.
      The type of serum employed generally did not affect the response to inducers of
      differentiation. No significant inhibition of the recovery of granulocyte
      macrophage colony-forming units was determined by the five inducers in
      experiments with three normal bone marrow samples. Our experiments indicate that
      biological differentiation inducers can reduce AML CFU-L self-renewal and
      increase the proportion of differentiated cells at concentrations that do not
      affect normal myelopoiesis and could be achieved during treatments in vivo.

PMID- 1372668
TI  - Modulation of granulocyte LAM-1 and MAC-1 during dialysis--a prospective,
      randomized controlled trial.
AB  - Hemodialysis with first-use cellulosic dialysis membranes results in activation
      of the alternative pathway of complement and profound neutropenia followed by
      rebound leukocytosis. The neutropenia has been shown to be associated with
      increased expression of adhesion receptors and pulmonary sequestration of
      granulocytes. However, the mechanism underlying the return of the granulocytes
      has not been elucidated. We determined simultaneously the changes in the
      granulocyte adhesion receptor MAC-1 (CD11b-CD18) and the selectin LAM-1 receptor
      during dialysis using a complement activating and a non-complement activating
      membrane, in a randomized, cross-over study. With initiation of dialysis with
      cellulosic membranes, there was a rapid and prominent increase in the expression
      of MAC-1 receptors. At the nadir of granulocyte count, 15 minutes after
      initiation of dialysis with the complement activating membrane, there was a four
      fold increase in the MAC-1 receptor expression. At the same time, there was a two
      fold decrease in LAM-1 expression. There were no changes in the expression of two
      other granulocyte receptors CD11a and CD15 which are known not to be modulated
      during granulocyte activation. Granulocytes harvested during dialysis and which
      had high MAC-1 and low LAM-1 expression had a significantly decreased adherence
      to endothelial cell monolayers. Dialysis of the same patients with non-complement
      activating membranes resulted in no significant change in the expression of these
      receptors on granulocytes nor in their adherence to endothelial cells. These
      results shed new light on the mechanism of the cyclical granulocytopenia and
      rebound granulocytosis during dialysis with new cellulosic membranes.

PMID- 1372671
TI  - [Myeloid growth factors can cure chronic neutropenia and facilitate cytostatic
      therapy].

PMID- 1372670
TI  - Molecular investigation of the cytokines produced by normal and malignant B
      lymphocytes.
AB  - Different normal and malignant human B-cell populations were studied with a
      twofold aim: to define which cytokines are produced in vivo, and to assess the
      relationship between cytokine production and kinetic state. To analyse normal B
      cells representative of different stages of activation and proliferation in vivo,
      we purified germinal centre (GC)-B blasts and mantle B (M-B) cells from tonsils.
      To compare malignant B lymphocytes with their closest normal equivalent cells, we
      separated malignant CD5+B lymphocytes from the peripheral blood of patients with
      B-chronic lymphocytic leukemia (B-CLL) and normal CD5+B lymphocytes from cord
      blood. The expression of interleukins (IL) IL-1 alpha, IL-1 beta, tumour necrosis
      factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), IL-2, IL-4,
      and IL-6 genes was analysed using Northern and Western blotting techniques. TNF
      alpha mRNA is produced by resting (M-B) and actively proliferating (GC-B) normal
      B lymphocytes. TGF-beta mRNA is present at high levels in resting normal M-B
      cells, while the transcript levels are lower in proliferating GC-B and in
      activated CD5+B lymphocytes. IL-2 production is limited to the actively
      proliferating GC-B blasts, IL-1 beta and IL-6 to resting M-B cells. The cytokine
      production profile of CD5+ malignant B-CLL cells differs from that of their
      putative normal counterparts and is more like the profile of M-B cells, since B
      CLL cells produce IL-1 beta, TNF-alpha, TGF-beta, and IL-6. These observations
      lead to the following conclusions: among normal B lymphocyte populations, resting
      M-B lymphocytes are the most active cytokine producers, and B-CLL malignant B
      cells reflect the production pattern of normal resting B lymphocytes.

PMID- 1372674
TI  - Control of functional mRNA stability in bacteria: multiple mechanisms of
      nucleolytic and non-nucleolytic inactivation.
AB  - Messenger RNA in bacteria may be inactivated by several parallel mechanisms
      acting independently on different target sites. For any species of mRNA the
      overall rate of inactivation is determined by the sum of the contributions from
      the different mechanisms. Transcripts may be inactivated directly by
      endonucleolytic attack or by processive nucleolytic degradation, which may
      proceed in the 3'-5' direction and probably also in the 5'-3' direction.
      Moreover, the functional lifetime of many mRNAs may be determined by processes
      that are not nucleolytic, such as the binding of translational repressors or the
      formation of secondary structures which prevent initiation of translation. These
      non-nucleolytic processes may also determine the chemical stability as chemical
      degradation frequently appears to be closely coupled to functional inactivation.
      The relative importance of the different mechanisms in the inactivation of bulk
      cellular mRNA, as well as the general prospects for engineering of stable mRNAs
      are discussed.

PMID- 1372672
TI  - [A follow-up of leukemia and drivers is needed].

PMID- 1372673
TI  - Suppression of nigrostriatal and mesolimbic dopamine release in vivo following
      noradrenaline depletion by DSP-4: a microdialysis study.
AB  - Pretreatment of rats with the noradrenergic neurotoxin DSP-4 selectively reduced
      regional levels of noradrenaline in the brain by more than 75%, and decreased the
      concentration of endogenous DA in microdialysates of the caudate nucleus and
      nucleus accumbens by 52% and 28%, respectively. Results support the hypothesis
      that central noradrenergic mechanisms facilitate nigrostriatal and mesolimbic
      dopamine transmission in vivo.

PMID- 1372676
TI  - Sequence diversity of the 1.3 kb retron (retron-Ec107) among three distinct
      phylogenetic groups of Escherichia coli.
AB  - In the preceding paper, we showed that a new 1.3 kb retron (retron-Ec107) in
      Escherichia coli is responsible for the biosynthesis of a branched-RNA-linked
      multicopy single-stranded DNA (msDNA-Ec107). Here, we show that this retron
      occurs in strains from different branches, A, B1, and D of a well-defined
      phylogenetic tree of a collection of wild E. coli. Sequence comparisons of the
      retrons from these three branches were carried out. Sequence homology was well
      conserved among the strains within the same branch and the retron sequence from
      branch A was exactly the same with that from branch D, while there were 18 base
      substitutions between the retrons from branch B1 and A or D, resulting in seven
      amino acid substitutions in reverse transcriptase. No substitutions were found in
      the msDNA- and msdRNA-coding regions, and there was no difference in the ability
      of msDNA production between them. These results suggest that the retron has
      probably been integrated into at least one of the three branches at an early
      stage of evolution and subsequently transferred to the other two branches, and
      also that the msDNA-producing system has been conserved during evolution with
      some mutations in the retron.

PMID- 1372675
TI  - Retron-Ec107 is inserted into the Escherichia coli genome by replacing a
      palindromic 34bp intergenic sequence.
AB  - Some natural isolates of Escherichia coli have been shown to produce a unique
      branched RNA-linked single-stranded DNA called msDNA. These bacteria contain a
      retro-element called retron consisting of the msr-msd region and the gene for
      reverse transcriptase (RT). All three E. coli retrons characterized to date have
      been shown to be integrated into a prophage or to be associated with phage
      related genes. In this report, we identified a new msDNA from an E. coli wild
      strain. Using the msDNA as a probe, the retron for the msDNA was cloned and its
      DNA sequence was determined. The retron was found to consist of a 1.3kb DNA
      fragment, making it the smallest retron isolated to date. The msDNA produced from
      the retron consists of a 107 base single-stranded DNA, which is considered to be
      branched out from the 18th G residue of a 75-base RNA molecule by a 2',5'
      phosphodiester linkage. Thus, the msDNA and the retron were designated msDNA
      Ec107 and retron-Ec107, respectively. Most significantly, retron-Ec107 was
      inserted into the E. coli genome by replacing a 34bp intergenic sequence between
      the pyrE and ttk genes located at 82 min on the E. coli chromosome.
      Interestingly, the retron contains palindromic structures at both ends and the E.
      coli 34bp intergenic sequence also contains a 10bp inverted repeat structure.
      These palindromic structures might have played a role in the integration of
      retron-Ec107 into the E. coli genome.

PMID- 1372677
TI  - Regulation of the expression of the cell-cycle gene ftsZ by DicF antisense RNA.
      Division does not require a fixed number of FtsZ molecules.
AB  - We show that the 53-nucleotide RNA molecule encoded by gene dicF blocks cell
      division in Escherichia coli by inhibiting the translation of ftsZ mRNA. Such a
      role for dicF had been predicted on the basis of the complementarity of DicF RNA
      with the ribosome-binding region of the ftsZ mRNA. An analysis of ftsZ expression
      at its chromosomal locus, and of an ftsZ-lacZ translational fusion controlled by
      promoters ftsZ1p and ftsZ2p only, indicates that ftsZ is not autoregulated.
      Partial inhibition of FtsZ synthesis leads to increased cell size. However, the
      number of FtsZ molecules per cell can be reduced threefold without affecting the
      division rate significantly. Our results suggest that septation is not triggered
      by a fixed number of newly synthesized FtsZ molecules per cell.

PMID- 1372678
TI  - Regulatory mutants and transcriptional control of the Serratia marcescens
      extracellular nuclease gene.
AB  - The extracellular nuclease of Serratia marcescens is regulated in a complex
      fashion. Unlike most catabolic enzymes, it appears not to be substrate regulated.
      However we have shown it to be regulated by an SOS-like system in S. marcescens.
      Additionally nuclease expression is regulated in a growth-phase-dependent manner.
      In this work we demonstrate that growth-phase-dependent regulation is at the
      transcriptional level. The putative LexA-binding site which mediates SOS
      regulation is shown to act as an operator site in vivo. The boundaries of a
      minimal promoter, still regulated by growth phase and SOS regulation, are defined
      along with the transcriptional start site. However, a region upstream of the
      nuclease promoter is shown to enhance significantly the expression of nuclease.

PMID- 1372681
TI  - Selected poster abstracts of the 21st annual meeting of the European
      Environmental Mutagen Society. 25-31 August 1991, Prague, Czechoslovakia.

PMID- 1372679
TI  - Monoclonal antibodies specific to porin of Haemophilus influenzae type b:
      localization of their cognate epitopes and tests of their biological activities.
AB  - The major outer membrane protein of Haemophilus influenzae type b (Hib) is porin
      (Mr 38,000, 341 amino acids). To identify antigenic determinants on Hib porin
      that might be exposed at the bacterial cell surface, seven mouse monoclonal anti
      Hib porin antibodies were generated. The monoclonal antibodies were tested for
      their binding to intact cells by flow cytometry; all but one bound to the cell
      surface. Digestions of Hib porin with cyanogen bromide, hydroxylamine or trypsin
      generated fragments, the identities of which were confirmed by microsequencing of
      the amino termini. Following electrophoresis and immunoblotting of the fragments,
      the specificities of the monoclonal antibodies for their cognate sequences were
      determined. The porin gene ompP2 was expressed in the baculovirus expression
      vector system; the recombinant porin was recognized by all of the monoclonal
      antibodies. Deletions were created by omega mutagenesis of ompP2, generating
      proteins truncated after amino acids 139, 174, 182, and 264. These deletion
      proteins were tested for reactivities with the monoclonal antibodies, thereby
      establishing the boundaries of three antigenic determinants that were recognized
      by the monoclonals: domain (i), amino acids 104-139; domain (ii) amino acids 162
      174; and domain (iii), amino acids 267-341. The biological activities of
      monoclonal antibodies that were representative of these three classes were tested
      for their bactericidal activity in complement-mediated lysis of whole cells. The
      monoclonal antibodies were also tested for their immunoprotective properties in
      the infant rat model of bacteraemia. Although the monoclonal antibodies were
      surface-binding, they were neither bactericidal nor protective.

PMID- 1372680
TI  - High-dose combination alkylating agents with autologous bone-marrow support in
      patients with breast cancer: preliminary assessment of DNA damage in individual
      peripheral blood lymphocytes using the single cell gel electrophoresis assay.
AB  - The single cell gel (SCG) assay is a sensitive electrophoretic technique for
      detecting the presence of DNA single strand breaks and alkali-labile damage in
      individual cells. This technique was used to evaluate the levels of DNA damage in
      cryopreserved peripheral blood lymphocytes (PBLs) from 11 breast cancer patients
      treated with high doses of cyclophosphamide and cisplatin and provided autologous
      bone marrow transplantation after treatment. PBL specimens for the SCG study were
      obtained just prior to treatment, following the administration of
      cyclophosphamide and cisplatin for 2 days, and upon lymphocytic recovery. Based
      on a concurrent analysis of DNA damage in cryopreserved and non-cryopreserved PBL
      samples from three patients, the mean level of DNA migration or the dispersion of
      damage among cells was not affected by the process of cryopreservation. The pre
      treatment samples of several patients contained PBL with increased levels of DNA
      damage, presumably reflecting persistent DNA damage induced by previous treatment
      regimens. Chemotherapy resulted in a significant but variable increase in DNA
      damage in PBL samples from all patients. In this limited study, the level of
      damage did not correlate with serum levels of cyclophosphamide or with lymphocyte
      toxicity. Among the post-treatment samples, increased levels of DNA damage were
      absent in most but not all patients. The presence of damaged cells in the post
      treatment samples may be indicative of an inadequate therapy regimen or of DNA
      damage resulting from non-therapy related processes. Because of its simplicity
      and short processing time, the SCG assay can be used to evaluate levels of DNA
      damage during the course of therapy, allowing the dose schedule to be altered to
      achieve a desired effect level.

PMID- 1372682
TI  - The ability of liver extracts from different-aged rats to repair 'mis
      instructive' and 'non-instructive' lesions of DNA.
AB  - The ability to repair 'mis-instructive', O6-methylguanine, and 'non-instructive',
      AP sites, DNA lesions in Fischer 344 rat livers at various ages was determined.
      Different behaviours were observed. While the AP-endodesoxyribonuclease enzymes
      displayed a high constant level throughout the animals' lifetime, the O6
      methylguanine-DNA methyltransferase activity presented a stepwise modulation (DNA
      normalisation of results): the O6-MT activity significantly increased within the
      first month of animal life and enhanced again after 6 months reaching a maximum
      plateau in the 12-18-month-old animals. Thereafter a net significant decrease of
      O6-MT enzyme was detected in the 24-month-old group. While the repair of the
      widely formed AP sites appeared uniformly efficient like 'house keeping'
      functions, the removal of the rare precancerous O6-methylguanine is age-dependent
      indicating a decreased protection of the youngest and oldest animals against this
      'mis-instructive' damage. However, any extrapolation of the age-associated cancer
      risk needs further assessment.

PMID- 1372683
TI  - Demethylation of satellite I DNA during senescence of bovine adrenocortical cells
      in culture.
AB  - Over the finite proliferative life span of cultured bovine adrenocortical cells,
      satellite I DNA shows a progressive and extensive loss of methylation at CCGG
      sites. This was shown by Southern blotting after digestion with the methylation
      sensitive enzyme HpaII alone, which provides a sensitive indicator of methylation
      loss, or digestion with the combination of EcoRI and HpaII, which provides a
      quantitative indication of loss of methylation. Bovine tissues, including adrenal
      cortex, all showed a much higher level of satellite methylation than cultured
      adrenocortical cells. After adrenocortical cells are placed in culture, some
      demethylation of satellite I is seen as early as 10 population doublings. By 80
      population doublings, loss of satellite DNA methylation is extensive. The loss
      does not appear to prevent continued cell division, since an extended life span
      clone of bovine adrenocortical cells transfected with SV40 T antigen showed a
      similar pattern of extensive demethylation. Satellite demethylation has been
      reported in aging in vivo and the present cell culture system may provide an in
      vitro model for this form of genetic instability.

PMID- 1372684
TI  - The effect of aging on cell-cycle kinetics and X-ray-induced chromosome
      aberrations in cultured lymphocytes from patients with Down syndrome.
AB  - To evaluate the effects of aging on cytogenetic characteristics of lymphocytes
      from Down syndrome (DS), cell-cycle kinetics after PHA stimulation and chromosome
      type aberration frequencies after X-ray exposure were investigated in vitro in
      the lymphocytes derived from 4 (or 3 for X-ray treatment) age groups of DS
      patients and age-matched controls. The results clearly showed higher mitotic and
      proliferation index levels in younger groups compared to older groups at the
      various culture intervals, whether the lymphocytes were from the DS patients or
      controls. The age-related changes of the proliferation index were mainly
      attributed to a delayed response to PHA as age increased. The changes of PHA
      responses seemed to be particularly marked during adolescence. Nonetheless, no
      significant differences were observed between the DS patients and age-matched
      controls for each age group. In all age groups, frequencies of both chromosome
      type exchanges and deletions were elevated in the DS patients by about 1.3 times
      in comparison with the controls. The magnitude of radiosensitivity, however,
      seemed to decrease slightly in the 40-49-year group. To our knowledge, the
      present study is the first report in the literature to deal with the effect of
      aging on the greater radiosensitivity of DS lymphocytes.

PMID- 1372685
TI  - Effect of iron chelators on the cytotoxic and genotoxic action of hyperoxia in
      Chinese hamster ovary cells.
AB  - The iron chelators o-phenanthroline and desferrioxamine were tested for their
      ability to protect Chinese hamster ovary cells against the cytotoxic and
      genotoxic effects of normobaric hyperoxia. Desferrioxamine added at sub-toxic
      concentrations (up to 2.5 microM) over a period of several days had no protective
      effect on hyperoxia-induced clonogenic cell killing and growth inhibition. The
      clastogenic effect of hyperoxia was strongly potentiated by desferrioxamine,
      while the induction of sister-chromatid exchanges (SCEs) by hyperoxia was
      unaffected. Similarly, o-phenanthroline (up to 0.25 microM) had no protective
      effect on hyperoxia-induced cell killing, growth inhibition, and SCE induction,
      while also this compound potentiated the clastogenic effect of hyperoxia. These
      results do not support a critical role for cellular iron in the mechanism of
      toxicity by normobaric hyperoxia in CHO cells. However, the results may still be
      consistent with a critical involvement of particular iron fraction(s) not
      susceptible to the chelators used. Furthermore, our results show that
      concentrations of iron chelators known to protect against short-term (up to 1 h)
      toxic exposure to oxidative stress become toxic themselves when applied
      chronically, i.e., in the order of days.

PMID- 1372686
TI  - Effects of mutagens on the clonal lifespan of Paramecium tetraurelia.
AB  - There has been interest in the phenomenon that a cell cannot undergo unlimited
      reproduction under adequate conditions and undergoes senescence. In holotrichous
      ciliates, Paramecium has a limit of vegetative reproduction without sexual
      reproduction but Tetrahymena does not always have a limited lifespan. Comparing
      the two species would increase our knowledge of the mechanism of cellular clonal
      aging. We previously showed that mutations induced by X-rays shorten clonal
      lifespan. In this study, we examined whether mutagens shorten the clonal lifespan
      of Paramecium tetraurelia. P. tetraurelia was exposed to the alkylating agent N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG), 0.045 mg/ml, for 30 min. The animal
      was exposed to MNNG 6 times in total while young (under 80 divisions from the
      start of a clonal life cycle) or 4 times during the senescent stage. MNNG
      shortened the clonal lifespan as expressed by the decrease in fission number from
      186 +/- 55 (4 cell lines) to 136 +/- 21 (6 cell lines) with the first two
      treatments but with further exposures the lifespan increased to 182 +/- 15 (5
      cell lines). MNNG had no effect when administered at the older age. Exposure of
      P. tetraurelia to 4-nitroquinoline-N-oxide at 0.021 mg/ml twice for 12 and 15 min
      at the younger age reduced the mean clonal lifespan from 143 +/- 28 to 125 +/- 21
      and the maximum lifespan from 263 +/- 33 to 175 +/- 25.

PMID- 1372687
TI  - Modulation of DNA modification (I-compound) levels in rat liver and kidney by
      dietary carbohydrate, protein, fat, vitamin, and mineral content.
AB  - I-compounds are DNA modifications detected by 32P-postlabeling that increase with
      age in rodents without known carcinogen exposure. Diet type (natural ingredient
      versus purified) greatly influences patterns and levels of I-compounds. To test
      the hypothesis that I-compound formation is affected, also, by dietary macro- and
      micronutrients, effects of carbohydrate, protein, fat, vitamin, and mineral
      content on rat liver and kidney I-compounds were determined. Female Sprague
      Dawley rats were fed basic or modified AIN-76A purified diets for 3-6 months.
      High protein (HP) diet (50%, w/w) increased I-compound levels in liver but not
      kidney. High carbohydrate (HC) diet (78%) produced a significant increase in the
      polar as well as total I-compound levels in both tissues. High fat diets (20%)
      elicited significantly lower levels of liver I-compounds than HC, HP, and basic
      diets. There were few significant differences between high polyunsaturated
      (safflower oil) and saturated fat (lard) diet groups. No qualitative differences
      in I-compound profiles were observed in either tissue. In rats fed basic diet
      supplemented with vitamins and/or minerals, increased vitamin content reduced the
      levels of polar I-compounds in liver. No extra diet-induced adducts were
      observed; all effects were of a quantitative nature. These data provide direct
      evidence that nutrients significantly influence I-compound levels and support the
      hypothesis that normal metabolism of nutrients leads to the production of small
      amounts of DNA-reactive electrophiles. These observations suggest a novel
      mechanism where nutrient composition of the diet may play a role in development
      of neoplasia and other adverse health effects.

PMID- 1372688
TI  - Different rate of chromosome breakage in human fibroblast strains after storage
      in liquid nitrogen.
AB  - Cytogenetic investigation was carried out on fibroblasts stored in liquid
      nitrogen during a period of 7-99 months. Cell strains were from 9 individuals, 2
      of whom were affected by xeroderma pigmentosum group C (XPC), and 2 XPC
      heterozygotes. In cell samples from 3 normal subjects and from 1 patient, high
      frequencies of abnormal mitoses were observed at the first passage after thawing,
      which returned to normal values after a few subcultures. The most frequent
      lesions were chromosome gaps and breaks. The cells damaged the most were those
      from one XP patient. These findings indicate that cells from some individuals are
      hypersensitive to clastogenic factors acting during freezing and thawing
      procedures. This sensitivity could be related to the genetic constitution,
      although the XP homozygous condition is not an essential or sufficient factor.

PMID- 1372690
TI  - Micronucleus test with ethyl methanesulfonate in mouse peripheral blood
      reticulocytes stained supravitally using acridine orange-coated slides.
AB  - A new method for the micronucleus test using peripheral blood reticulocytes
      stained supravitally using acridine orange-coated slides was evaluated in male CD
      1 mice treated with ethyl methanesulfonate (EMS) at doses of 100, 200, 300, and
      400 mg/kg. Peripheral blood samples were taken 0, 24, 48, 72, and 96 h after
      treatment from each mouse without killing. The frequencies of micronucleated
      reticulocytes increased dose-dependently with the peak at 48 h after treatment.
      These results indicate that, at least for EMS, the new method used here can be an
      alternative to the conventional method using bone marrow polychromatic
      erythrocytes.

PMID- 1372689
TI  - Simplified mouse peripheral reticulocyte micronucleus test with
      dimethylnitrosamine.
AB  - The induction of micronuclei by treatment with dimethylnitrosamine was evaluated
      and compared in peripheral blood and bone marrow cells of male CD-1 mice.
      Peripheral blood preparations were made on acridine orange (AO)-coated slides and
      scanned by fluorescence microscopy. A significant increase in micronuclei was
      observed 24 h after treatment in bone marrow polychromatic erythrocytes, and 24
      48 h after treatment in peripheral reticulocytes. The peak frequency of
      micronuclei in peripheral reticulocytes was delayed by about 24 h relative to
      bone marrow polychromatic erythrocytes. This micronucleus test using peripheral
      blood was shown to be easy to do and as sensitive as the test using bone marrow
      cells. From this result, it is concluded that the method with AO-coated slides
      and peripheral blood is as suitable as bone marrow cells for the micronucleus
      assay.

PMID- 1372691
TI  - Micronucleus tests on N-ethyl-N-nitrosourea with mouse peripheral blood
      reticulocytes using acridine orange-coated slides.
AB  - The micronucleus test with peripheral blood using acridine orange-coated slides
      was validated in male CD-1 mice treated once with N-ethyl-N-nitrosourea (ENU) at
      doses of 6.25, 12.5, 25.0, and 50.0 mg/kg body weight. Peripheral blood
      preparations were made 0, 24, 48, and 72 h after treatment. The frequencies of
      micronucleated peripheral reticulocytes in the ENU-treated groups increased dose
      dependently, peaking at 48 h after treatment. The results indicate that the
      method used in the present study can be an alternative to the method using bone
      marrow polychromatic erythrocytes.

PMID- 1372692
TI  - The micronucleus test of methyl methanesulfonate with mouse peripheral blood
      reticulocytes using acridine orange-coated slides.
AB  - The usefulness of the micronucleus assay using mouse peripheral blood
      erythrocytes and acridine orange (AO)-coated slides was evaluated with methyl
      methanesulfonate (MMS). The micronucleus test was carried out at doses ranging
      from 20 to 80 mg/kg body weight in CD-1 mice by intraperitoneal injection.
      Peripheral blood cells were examined from 0 to 72 h after treatment at 12- or 24
      h intervals. Bone marrow cells from other mice treated with 80 mg/kg MMS were
      also sampled at the same times. The frequency of micronucleated reticulocytes
      (MNRETs) increased dose-dependently at every sampling time except 72 h, and the
      maximum frequency of MNRETs was observed at about 36 h after treatment.
      Micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow after a dose of
      80 mg/kg were significantly induced at 12 h to 36 h, and the maximum frequency of
      MNPCEs was observed at 24 h after treatment. The induction of MNRETs was delayed
      by about 12 h compared to that of MNPCEs in bone marrow, and the maximum
      frequencies of MNRETs were lower than those of MNPCEs, but the induction of
      MNRETs by MMS was significant and dose-dependent. It is concluded, therefore,
      that bone marrow cells could be replaced by peripheral blood cells as material
      for the micronucleus assay using AO-coated slides.

PMID- 1372693
TI  - The micronucleus test with mouse peripheral blood on N-methyl-N'-nitro-N
      nitrosoguanidine and mitomycin C.
AB  - The micronucleus test using mouse peripheral blood was conducted with N-methyl-N'
      nitro-N-nitro-soguanidine (MNNG) and mitomycin C (MMC) as part of the 5th
      collaborative study supported by the Environmental Mutagen Society of Japan
      (CSGMT/MMS.JEMS). Male CD-1 mice were intraperitoneally injected once with 12.5
      100 mg/kg of MMC. Peripheral blood was drawn at different intervals after
      treatment, placed on slides previously coated with acridine orange and the
      numbers of reticulocytes with micronuclei (MNRETs) were scored. The experiments
      indicated that the maximum effect of both MNNG and MMC was found about 48 h after
      treatment, and that the micronucleus test using peripheral blood is useful for
      the screening of chemicals throughout the experimental period in a single animal.

PMID- 1372694
TI  - The micronucleus assay with mouse peripheral blood reticulocytes using acridine
      orange-coated slides with triethylenemelamine.
AB  - A micronucleus assay using mouse peripheral blood and supravital staining with
      acridine orange (AO) was validated by two laboratories on triethylenemelamine
      treated mice. Dose- and time-dependent increases in micronucleated peripheral
      reticulocytes were observed. This new method can be used as an alternative to the
      conventional bone marrow micronucleus assay.

PMID- 1372696
TI  - Micronucleus assays on 5-fluorouracil and 6-mercaptopurine with mouse peripheral
      blood reticulocytes.
AB  - As part of the 5th collaborative study of the Collaborative Study Group for the
      Micronucleus Test (CSGMT), the sensitivity and advantages of the micronucleus
      assay using mouse peripheral blood cells were evaluated using 5-fluorouracil (5
      FU) and 6-mercaptopurine (6-MP). The peripheral blood cells were collected from a
      tail vein of CD-1 male mice just before and 24-120 h after intraperitoneal
      injection. At 24-h intervals. The maximum incidence of micronucleated
      reticulocytes (MNRETs) at 50 mg/kg 5-FU was observed 96 h after injection; at 100
      mg/kg, the peak was delayed to 120 h, and followed severe bone marrow depression.
      With 6-MP, maximum MNRETs were observed 48 h after treatment at all doses tested.
      At dose levels higher than 50 mg/kg, severe bone marrow depression was observed
      after maximum MNRETs. Though the appearance patterns of MNRETs and the bone
      marrow depression were different between 5-FU and 6-MP, the positive response of
      both chemical could be detected with this assay system as well as with the
      micronucleus test using femoral bone marrow cells.

PMID- 1372695
TI  - The micronucleus assay with peripheral blood reticulocytes by acridine orange
      supravital staining with 1-beta-D-arabinofuranosylcytosine.
AB  - Dose-dependent induction of micronuclei with 1-beta-D-arabinofuranosylcytosine
      (ara-C) was clearly shown in CD-1 mouse peripheral blood reticulocytes (RETs)
      using an acridine orange (AO) supravital staining method, as well as in the
      conventional bone marrow assay. The maximum frequencies of micronucleated RETs
      (MNRETs) in peripheral blood and of micronucleated polychromatic erythrocytes
      (MNPCEs) in bone marrow were comparable, as shown in two laboratories
      independently. The maximum frequencies of MNRETs in peripheral blood lagged about
      24 and 12 h behind those of MNPCEs in bone marrow in experiments with 24- and 12
      h sampling intervals, respectively. The proportion of each type of RET was
      examined periodically after treatment with ara-C at doses ranging from 6.25 to
      50.0 mg/kg. The proportion of type I RETs among total RETs decreased 24 or 48 h
      after treatment according to the dose level. This suggest that this ratio could
      be a good indicator of the bone marrow cell toxicity of test chemicals.

PMID- 1372697
TI  - The micronucleus test using peripheral blood reticulocytes from methotrexate
      treated mice.
AB  - The induction of micronuclei by methotrexate (MTX) was examined in two
      laboratories using mouse peripheral blood reticulocytes. MTX was a weak inducer
      in the micronucleus test using bone marrow cells and single treatments, and was
      one of the few chemicals showing a multiple-treatment effect (CSGMT/JEMS.MMS,
      1990). In our preliminary experiments, the ratio of reticulocytes to total
      erythrocytes decreased greatly after a single treatment with MTX at 100 mg/kg, so
      lower dose levels of MTX were selected to carry out the micronucleus test in
      peripheral blood. Full-scale tests were performed at dose levels of 0, 10, 20,
      40, and 80 mg/kg, with five sampling times of 0, 24, 48, 72, and 96 h.
      Frequencies of micronucleated reticulocytes (MNRETs) increased dose-dependently
      at 72 h, to a maximum of approximately 1%; some preparations obtained from the
      animals at higher doses could not be examined because the ratio of reticulocytes
      to total erythrocytes had decreased severely. At doses of 0.5-4.0 mg/kg, the
      effect of multiple treatments vs. single treatments was not clear, nor was the
      maximum level of response much different. Since MTX induced a clear positive
      response in peripheral blood reticulocytes after a single treatment, the
      reticulocytes in peripheral blood seem a more sensitive target.

PMID- 1372698
TI  - The mouse peripheral blood micronucleus test with 2-acetylaminofluorene using the
      acridine orange supravital staining method.
AB  - The peripheral blood micronucleus test using the acridine orange (AO) supravital
      staining method was validated with the potent bone marrow clastogen 2
      acetylaminofluorene (2-AAF). 2-AAF induced micronuclei in peripheral blood
      reticulocytes dose-dependently as well as in bone marrow polychromatic
      erythrocytes. The incidence of micronucleated reticulocytes (MNRETs) peaked 48 h
      after a single treatment in both CD-1 and BDF1 mice, and the incidence of
      micronucleated polychromatic erythrocytes (MNPCEs) peaked 24 or 48 h after
      treatment. The maximum incidences of MNRETs were always higher than those of
      MNPCEs in both mouse strains treated once. In the double-treatment regime, the
      maximum incidence of MNRETs was observed at 24 h after the second treatment in
      each strain. The incidences of MNRETs in BDF1 mice were higher than in CD-1 mice
      after a single treatment but were comparable after double treatment. These
      results indicate that the peripheral blood micronucleus test using AO supravital
      staining is as sensitive as the conventional bone marrow assay. The new staining
      method can be performed more easily than the original smear method using either
      bone marrow or peripheral blood cells. Thus, the peripheral blood method using AO
      supravital staining is a possible alternative to the conventional bone marrow
      assay.

PMID- 1372700
TI  - The micronucleus test of benzo[a]pyrene with mouse and rat peripheral blood
      reticulocytes.
AB  - The micronucleus test using peripheral blood reticulocytes (RETs) was evaluated
      in CD-1 and BDF1 mice and Sprague-Dawley rats treated with benzo[a]pyrene at two
      independent laboratories. The maximum incidence of micronucleated reticulocytes
      (MNRETs) appeared in both strains of mice 48 h after the treatment;
      interlaboratory differences were small. The incidence of MNRETs in BDF1 mice was
      higher than in CD-1 mice. In rats, significant increases of MNRETs with the
      maximum response at 72 h were detected when B[a]P was administered i.p.; slight
      but significant increases were observed at 24 h or later, with the maximum at 24
      48 h, when it was administered p.o. These results suggest that the new method for
      the micronucleus test using circulating RETs will be useful in the detection of
      the clastogenicity of chemicals.

PMID- 1372701
TI  - Micronucleus induction in mouse peripheral reticulocytes by 7,12
      dimethylbenz[a]anthracene.
AB  - Micronucleus assays using mouse peripheral blood stained vitally on acridine
      orange (AO)-coated slides were evaluated at two laboratories with 7,12
      dimethylbenz[a]anthracene (DMBA) and compared with the standard bone marrow
      assay. DMBA was administered by single intraperitoneal injection to CD-1 mice at
      doses ranging from 5 to 80 mg/kg, then 5 microliters of peripheral blood was
      sampled from a tail vein at 24, 48, 72, 96, and 120 h after treatment. Similar
      incidences of micronucleated young erythrocytes were observed in peripheral blood
      reticulocytes and bone marrow polychromatic erythrocytes. The dose response of
      micronucleated reticulocytes was delayed compared to that of micronucleated
      polychromatic erythrocytes. The dose-response curves after treatment with DMBA
      differed depending on the sampling times, which revealed the difficulty of
      obtaining accurate dose-response relations in the micronucleus assay. The present
      result demonstrated that the simple and rapid AO supravital staining method is a
      valuable and easier method for obtaining dose- and time-response data for
      quantification of micronucleus induction by chemicals.

PMID- 1372702
TI  - Detection of micronuclei in peripheral blood of mitomycin C-treated mice using
      supravital staining with acridine orange.
AB  - The induction of micronuclei in peripheral blood from mitomycin C (MMC)-treated
      mice was examined using a supravital acridine orange staining method. Male ICR
      mice were intraperitoneally given MMC at a single dose of 0.25, 0.5, 1, or 2
      mg/kg. Blood was sampled from the tail 24, 48, 72, and 96 h after treatment, and
      the frequency of micronucleated reticulocytes (MNRETs) was examined. The
      induction of MNRETs peaked at 48 h after treatment with MMC; there was a clear,
      dose-related increase in MNRETs. In a multiple-treatment study, mice were treated
      with 4 consecutive daily injections of MMC at a dose of 0.13, 0.25, 0.5, or 1
      mg/kg. The frequency of MNRETs increased markedly 24 h after the second treatment
      as compared with the first treatment, and did not change significantly until 24 h
      after the fourth treatment. The frequency of MNRETs decreased to approximately
      control values 96 h after the last treatment. In addition, a slight but
      statistically significant increase in the number of micronucleated normochromatic
      erythrocytes in peripheral blood was detected by means of Giemsa staining 7 days
      after the last treatment. These results confirm the usefulness of the supravital
      acridine orange staining method to evaluate micronucleus induction in mouse
      peripheral blood.

PMID- 1372699
TI  - The micronucleus test with peripheral reticulocytes from phenacetin-treated mice.
AB  - The in vivo micronucleus test is conventionally performed using mouse bone marrow
      cells (BM assay). Using phenacetin as a test chemical, an alternative method
      using reticulocytes (RET assay) was examined to determine if this could be
      substituted for the BM assay. Single doses of 400, 600, and 800 mg/kg gave
      negative results 24 h after i.p. administration, but positive results were
      obtained with 600 and 800 mg/kg after 48 h. Responses were weak at 72 h. Double
      treatment enhanced the responses; 400 mg/kg gave a positive result. Maximum
      responses were generally reached 24 h after the second treatment, 48 h if doses
      were highly toxic. When the BM and RET assays were compared, the BM assay seemed
      to be slightly more sensitive than the RET assay; double treatment was superior
      to a single treatment in both BM and RET assays. Both assays can be used
      routinely but in the RET assay, sequential samples can be obtained from the same
      individuals without killing them, providing a firm basis to substitute it for the
      BM assay. Taking advantage of this characteristic of the RET assay, a regimen of
      double treatments and double sampling at 24 and 48 h is recommended for a wide
      range of doses. These data were obtained with CD-1 mice; MS/Ae mice gave a higher
      incidence of micronuclei than did the CD-1 strain.

PMID- 1372705
TI  - Effects of benzene in a micronucleus test on peripheral blood utilizing acridine
      orange-coated slides.
AB  - A micronucleus test was conducted on the peripheral blood of mice and rats
      utilizing acridine orange-coated slides (AO-coated method) after oral
      administration of benzene. Blood was sampled at 0, 24, 48, and 72 h after
      administration of benzene at doses of 500, 1000, and 2000 mg/kg in both mice and
      rats. The highest occurrence of micronucleated reticulocytes (MNRETs) was
      observed at 48 h after administration in both species. Species differences was
      found in the frequency of MNRETs, with the number being lower in rats than in
      mice. The present results indicate that the micronucleus test can easily detect
      chromosome aberrations in peripheral blood induced by benzene administration in
      both mice and rats. Furthermore, the AO-coated method used in this study was
      simpler to perform and allowed for easier detection of the effect than the
      conventional method.

PMID- 1372703
TI  - Induction of micronucleated reticulocytes by potassium bromate and potassium
      chromate in CD-1 male mice.
AB  - Micronucleus tests of potassium bromate (KBrO3) and potassium chromate (K2CrO4)
      were conducted with peripheral blood reticulocytes (PB-RETs) of CD-1 male mice
      dose intraperitoneally. Peripheral blood cells collected from the tail were
      stained supravitally with acridine orange (AO) using AO-coated glass slides. Both
      KBrO3 and K2CrO4 induced micronuclei in PB-RETs in the same manner as in
      polychromatic erythrocytes of bone marrow.

PMID- 1372704
TI  - Micronucleus test with vincristine sulfate and colchicine in peripheral blood
      reticulocytes of mice using acridine orange supravital staining.
AB  - The induction of micronuclei in mouse peripheral blood reticulocytes (RETs) was
      studied with the spindle poisons vincristine sulfate (VINC) and colchicine (COL)
      using acridine orange (AO) supravital staining. Each chemical was studied
      independently in two laboratories using the same protocol. Blood samples were
      prepared at 0, 24, 48, and 72 h after a single intraperitoneal treatment with
      VINC (0.0625, 0.125, and 0.25 mg/kg) or COL (0.25, 0.5, 1.0, and 2.0 mg/kg). Both
      VINC and COL induced micronucleated RETs (MNRETs) significantly and dose
      dependently with a peak at 48 h after treatment. Maximum frequencies of
      micronucleated polychromatic erythrocytes (MNPCEs) were observed 24 h after
      treatment with VINC; thus, the transition time from MNPCEs to MNRETs was about 24
      h. Both spindle poisons gave comparable results in the paired laboratories,
      indicating that the present AO supravital staining method is highly reproducible.

PMID- 1372706
TI  - Micronucleus evaluation in peripheral blood reticulocytes of mice treated with
      procarbazine hydrochloride or mitomycin C.
AB  - The usefulness of the acridine orange (AO) supravital staining technique for the
      mouse peripheral blood reticulocyte micronucleus test was investigated
      independently by three laboratories using the known clastogens procarbazine
      hydrochloride (PCZ) and mitomycin C (MMC). In all three laboratories the highest
      frequencies of micronucleated peripheral blood reticulocytes were observed 48 h
      after treatment of mice with a single dose of either MMC or PCZ. The animals
      responded to both chemicals in a dose-dependent manner. Although similar
      qualitative results were observed, mean micronucleus frequencies induced by a
      particular dose of a given test chemical did vary quantitatively among the three
      laboratories. This was most probably due to the use of slightly different scoring
      criteria by each examiner. This aspect needs special attention. To minimize inter
      laboratory variability, therefore, we recommend establishing unequivocal criteria
      to distinguish the subclass of reticulocytes. These should then be used
      consistently by all investigators using this method. The most striking advantages
      of the AO supravital staining technique were the ease of slide preparation, the
      ease with which reticulocytes and mature erythrocytes could be distinguished by
      the examiners, and the occurrence of numerous scorable reticulocytes in each
      microscopic field, which greatly speeded up the manual counting process. The
      disadvantages of the staining technique were the limited scoring time due to the
      rapid fading of the fluorescence stain, the degradation of the cells with time,
      and the frequent need to search for adequate scoring areas within a microscopic
      field. Based on the data of this study the authors conclude that the AO
      supravital staining technique is highly suitable for the micronucleus assay in
      erythrocytic cells of mouse peripheral blood. In addition, we consider the mouse
      peripheral blood reticulocyte micronucleus test to be a useful tool with which to
      investigate the clastogenic potential of chemicals in vivo. As pretreatment of
      mice with Aroclor 1254 markedly increased the effect of PCZ on micronucleus
      induction, we suggest that the inclusion of inducers of drug metabolizing enzymes
      in the micronucleus test would be useful for the detection of the clastogenic
      potential of promutagenic chemicals.

PMID- 1372707
TI  - Validation of the mouse peripheral blood micronucleus assay using acridine orange
      supravital staining with urethane.
AB  - The mouse peripheral blood micronucleus assay using acridine orange supravital
      staining was compared with the standard bone marrow assay using urethane (ethyl
      carbamate)-treated mice. Urethane was intraperitoneally injected to CD-1 and BDF1
      mice at doses ranging from 62 to 1000 and 62 to 250 mg/kg, respectively.
      Peripheral blood was collected from the tail 0, 24, 48, and 72 h and bone marrow
      cells were smeared at 24 and 42 h after the treatment. Although the response of
      micronucleus induction in peripheral reticulocytes was delayed by about 24 h
      compared to that in bone marrow polychromatic erythrocytes, the maximum
      frequencies of micronucleated young erythrocytes were comparable. Therefore, the
      peripheral blood micronucleus assay using the acridine orange supravital staining
      method may provide a good alternative to the conventional bone marrow assay.

PMID- 1372708
TI  - The micronucleus assay using peripheral blood reticulocytes from mitomycin C- and
      cyclophosphamide-treated rats.
AB  - It used to be believed that the use of rat peripheral blood for the micronucleus
      assay would be difficult because micronucleated erythrocytes are captured and
      destroyed by the spleen quickly. We have applied an acridine orange (AO)
      supravital staining method to rat peripheral blood using AO-coated glass slides.
      Normal and splenectomized SD rats were treated once with mitomycin C (i.p.) or
      cyclophosphamide (p.o.), and 5 microliters of blood was collected at intervals
      from the tail vein between 0 and 72 h after treatment. For comparison, bone
      marrow cells were smeared conventionally 30 h after treatment. Although the
      frequencies of spontaneous and chemically induced micronucleated reticulocytes
      (MNRETs) from normal rats were lower on average in the highest dose group than
      those of splenectomized rats, the incidence of micronuclei among type I and II
      reticulocytes in normal rats at 48 h was almost identical to the incidence of RNA
      containing erythrocytes with micronucleus in bone marrow. Thus, we suggest that
      rat peripheral reticulocytes can be used as target cells for the micronucleus
      assay.

PMID- 1372709
TI  - Micronucleus test with mouse peripheral blood erythrocytes by acridine orange
      supravital staining: the summary report of the 5th collaborative study by
      CSGMT/JEMS.MMS. The Collaborative Study Group for the Micronucleus Test.
AB  - The main goal of the Collaborative Study Group for the Micronucleus Test (CSGMT)
      was to validate a new method for the micronucleus test, recently introduced by
      Hayashi et al. (1990), using mouse peripheral blood cells stained supravitally
      with acridine orange (AO). The micronucleus tests were performed on CD-1 mice
      using 23 chemicals with various modes of action. As a rule, one chemical was
      studied by two participants. Peripheral blood sampled from the same animal was
      examined 0, 24, 48, and 72 h (or longer) after treatment. The frequencies of
      micronucleated peripheral reticulocytes (MNRETs) were recorded based on
      observation of 1000 reticulocytes per mouse. All chemicals induced MNRETs dose
      dependently. Interlaboratory differences in the induction of MNRETs were in an
      acceptable range for most chemicals tested. Although differences were observed
      with some chemicals, there were no discrepancies in qualitative judgment. Most
      chemicals gave the greatest response 48 h after treatment, which was less
      variable than in the bone marrow assay (greatest response, 24-48 h). These
      results suggest that the peripheral blood assay using the AO supravital staining
      technique generates reproducible and reliable data to evaluate the clastogenicity
      of chemicals. This makes the peripheral blood micronucleus assay an attractive
      alternative to the conventional bone marrow assay.

PMID- 1372710
TI  - Micronucleus test with cyclophosphamide using mouse peripheral blood
      reticulocytes.
AB  - The usefulness of the micronucleus test using supravital staining of peripheral
      blood reticulocytes with acridine orange was evaluated in two laboratories after
      administering cyclophosphamide (CYP) as a model chemical by intraperitoneal
      injection (i.p.) to CD-1 mice. The frequencies of micronucleated peripheral
      reticulocytes (MNRETs) increased dose-dependently at each sampling time. There
      were no significant differences in the results obtained with this new method by
      the two laboratories. Although the induction of MNRETs was delayed by about 24 h
      compared to that of micronucleated polychromatic erythrocytes (MNPCEs) in the
      bone marrow, the frequencies of MNRETs and MNPCEs were almost identical at each
      optical sampling time, 24 h for MNPCEs and 48 h for MNRETs. Therefore, it is
      concluded that this method is a suitable alternative to that using femoral marrow
      cells.

PMID- 1372711
TI  - A mutation in the conserved helix termination peptide of keratin 5 in hereditary
      skin blistering.
AB  - In the hereditary blistering condition epidermolysis bullosa simplex, the skin
      blisters on trauma following rupture of epidermal basal cells. Clinical
      variations range from severely incapacitating, especially in early childhood, to
      mild forms that may not even present clinically. Dowling-Meara epidermolysis
      bullosa simplex is characterized by clusters of epidermal blisters and keratin
      clumping in the cytoplasm; recent reports describe potentially causal mutations
      in keratin 14 (refs 2, 3). Here we describe a 'complementary' mutation at the
      other end of the other keratin expressed by these cells (K5, coexpressed with
      K14), a change from a Glu to a Gly in the helix termination peptide, detected by
      altered antibody binding and confirmed by sequencing using the polymerase chain
      reaction. The two conserved helix boundary peptides are predicted to be essential
      for filament assembly, and the requirement for two complementary (type I and type
      II) keratins is absolute. Epidermolysis bullosa simplex diseases demonstrate the
      function of the keratin cytoskeleton in resisting compaction stresses which
      otherwise lead to cell lysis.

PMID- 1372714
TI  - Pathways of NH3/NH4+ permeation across Xenopus laevis oocyte cell membrane.
AB  - While acid loading with extracellular NH4Cl solutions usually first alkalinizes
      the cells through NH3 influx, and acidifies only when NH4Cl is removed, Xenopus
      oocytes became immediately acidic upon NH4Cl addition and the cells did not
      acidify further upon its removal. Since NH4Cl solutions also collapsed the
      membrane potential (Vm) and resistance (Rm), we conclude that primarily NH4+
      entered the cells where it liberated H+, with NH3 being trapped in intracellular
      lipid stores. To identify the NH4+ permeation pathway we have used K+ channel
      blockers (Ba2+, Cs+, tetraethylammonium, quinidine), various cation transport
      inhibitors (ouabain, bumetanide, amiloride) and other inhibitors, some of which
      block non-selective cation channels (La3+, diphenylamine-2-carboxylate, and p
      chloromercuribenzoate). However, only the latter substances partially prevented
      the collapse of Vm and Rm. This suggests, that NH4+ passes through non-selective
      cation channels. In accordance with the voltage dependence and/or stretch
      activation of such channels NH4+ fluxes appeared to be asymmetric. NH4+ influx,
      which depolarized and swelled the cells, was large and acidified rapidly, while
      the efflux, which repolarized and shrank the cells, was slow and alkalinized only
      slowly.

PMID- 1372715
TI  - Rate modulated DDD (i.e., DDDR) pacing.

PMID- 1372712
TI  - [Carcinoid tumors: current insights in biochemical and endocrine aspects,
      diagnosis and treatment].

PMID- 1372713
TI  - Anion channels in a human pancreatic cancer cell line (Capan-1) of ductal origin.
AB  - Transepithelial solute transport and bicarbonate secretion are major functions of
      pancreatic duct cells, and both functions are thought to involve the presence of
      chloride channels in the apical membrane of the cell. After being isolated from a
      human pancreatic adenocarcinoma, the Capan-1 cell line conserves most of the
      properties of ductal cells and thus constitutes a useful system for investigating
      the role of chloride channels. Using patch-clamp techniques, we identified three
      different chloride-selective channels in the apical membrane of confluent Capan-1
      cells. Two were non-rectifying chloride channels with low (50 pS) and high (350
      pS) unitary conductances. Both channels were active in cell-attached recordings,
      and they were consistently located together in the same patch. Maxi Cl- channels
      displayed multiple subconductance states, and were reversibly inactivated by
      either positive or negative voltage changes, which indicates that they were
      optimally opened at the cell resting potential. The third was an outwardly
      rectifying chloride channel with a unitary conductance of 38 pS and 70 pS at
      negative and positive potentials respectively. Rectifying Cl- channels were
      clustered in discrete loci. They were silent in situ, but became active after
      patch excision. In inside-out excised patches, the three channels displayed a
      high selectivity for Cl- over monovalent cations (Na+ and K+) and gluconate. They
      were blocked by 20-200 microM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid
      (DIDS) and were insensitive to changes in the Ca2+ concentration. Our results
      show that the apical membrane of Capan-1 cells contains a high density of
      chloride channels; these channels may provide pathways for transepithelial solute
      transport as well as for bicarbonate secretion.

PMID- 1372718
TI  - Late development of conduction block over the Mahaim fibers after electrical
      atrioventricular junction ablation for Mahaim fiber tachycardia.
AB  - A patient suffering from so called "Mahaim fiber" tachycardia is presented who
      developed complete heart block over Mahaim fibers after 18 months of AV junction
      ablation. Antegrade conduction along the Mahaim fiber was intact immediately
      after the procedure. This finding has not been previously described and suggests
      that permanent pacemaker implantation is mandatory in such patients.

PMID- 1372719
TI  - Safe introducer technique for pacemaker lead implantation.
AB  - Over the last several years, an introducer approach for pacemaker lead insertion
      has evolved that eliminates most introducer-related complications. The approach
      consists of defining a safe region for intrathoracic cannulation of the
      subclavian vein. If specific conditions cannot be met for entering the "safe"
      region or if the vein cannot be found, the subclavian vein is cannulated
      extrathoracically. Recently, this technique was used in 263 consecutive patients
      undergoing pacemaker implantation. The intrathoracic portion of the subclavian
      vein was used in 239 (90.9%) cases and the extrathoracic portion in 24 (9.1%).
      One hundred and ninety-eight (75.3%) cases were right-sided and 65 (24.7%) were
      left-sided. On the right side, 177 (89.4%) used the intrathoracic portion of the
      subclavian vein and 21 (10.6%) used the extrathoracic portion. On the left side,
      62 (95.4%) used the intrathoracic portion and three (4.6%) used the
      extrathoracic. The introducer technique was successful in all cases and there
      were no introducer-related complications.

PMID- 1372717
TI  - Prospective evaluation of heart block complicating early Lyme disease.
AB  - Lyme disease is a recognized cause of heart block/carditis. The incidence of
      heart block complicating early Lyme disease has not been prospectively evaluated.
      In this study, 61 patients with early Lyme disease documented by the rash of
      erythema migrans were prospectively evaluated for carditis. Fifty five of 61
      patients had a repeat examination 3 to 4 weeks after initiation of antibiotic
      therapy. Only one of 61 patients (1.6%) presented with heart block, which
      resolved with antibiotics. None of the 54 patients without heart block on initial
      presentation had a change in any measured electrocardiographic parameter or
      progressed to heart block after antibiotics. Therefore, early Lyme disease
      appears to be infrequently complicated by heart block. Early administration of
      antibiotics may prevent the development of heart block/carditis.

PMID- 1372716
TI  - The safety and efficacy of chronic ventricular pacing at 1.6 volts using a
      steroid eluting lead.
AB  - Steroid eluting leads may allow for lower chronic pacing thresholds and therefore
      lower pacing outputs. Twenty-two patients (15 presenting with syncope) were
      implanted with VVI or VVIR pacemakers and transvenous steroid eluting leads and
      followed for a mean of 20.6 months while being paced at 1.6 V and 0.6 msec. Mean
      acute voltage pacing thresholds were 0.40 V at 0.5 msec and chronic pulse width
      thresholds were 0.21 msec at 0.8 V. Pacemaker function was documented with one to
      three 24-hour Holter monitors, attached during the 2-6 week postimplant period,
      bimonthly transtelephonic monitoring, and monthly pacemaker clinic visits. No
      patient developed recurrent symptoms and consistent capture was verified in all
      patients on every 24-hour Holter recording and transtelephonic monitor. Chronic
      ventricular pacing at an output of 1.6 V at 0.6 msec is safe and effective when
      using a steroid eluting lead and potentially has implications for pacemaker
      longevity.

PMID- 1372720
TI  - Correlations between the localization of accessory atrioventricular pathway and
      Doppler indices of left ventricular output and function in patients with Wolff
      Parkinson-White syndrome.
AB  - Left ventricular (LV) output and function was investigated, using pulsed Doppler
      echocardiography in 52 patients with various localizations of accessory AV
      pathway (AP) in sinus rhythm and during paroxysm of AV reentrant tachycardia. In
      patients with sinus rhythm and ventricular preexcitation the most marked decrease
      in LV output and function (reduced aortic flow peak velocity [PV], mean
      acceleration [MA], stroke distance [SD], minute distance [MD], and lengthened
      time to peak velocity [TTP]) was noted in the presence of right parietal AP and
      less marked changes (decreased MA, lengthened TTP)--in the presence of
      posteroseptal AP, in comparison with the controls (P less than 0.005). During
      antidromic tachycardia the pronounced decrease in PV, MA, SD, and MD was noted,
      especially in patients with left parietal and posteroseptal AP, while in the case
      of right parietal AP changes in MA and MD were insignificant. During orthodromic
      tachycardia the decrease in LV function was less marked and no significant
      differences in the magnitude of LV output and function changes were found in
      various localizations of AP, except MA, which was more severely decreased in
      patients with posteroseptal AP. We conclude, that the alterations in Doppler
      indices of LV output and function are related to the localization of AP during AV
      reentrant tachycardia and regular sinus rhythm.

PMID- 1372722
TI  - Radiofrequency catheter ablation of an automatic atrial tachycardia in an adult.
AB  - Automatic atrial tachycardia (AAT) is often refractory to medical management.
      While surgical ablation and isolation procedures such as atrioventricular node
      ablation have been useful in the management of AAT, important limitations remain.
      Reported experience with catheter ablation of AAT is limited. This report
      describes the successful application of transvenous radiofrequency catheter
      ablation in an adult with AAT. Potential limitations of catheter ablation in the
      management of AAT are discussed.

PMID- 1372721
TI  - Optimized hemodynamics by implantation of a dual chamber pacemaker after
      heterotopic cardiac transplantation.
AB  - A patient who underwent prior heterotopic cardiac transplantation had persistent
      complaints of dyspnea, palpitations, and fatigue in spite of normal pump function
      of the donor heart. Repeated Holter monitoring excluded paroxysmal arrhythmias.
      It was thought that synchronization of both heart rates might alleviate his
      symptoms. The intrinsic heart rate of the donor heart was 90 beats/min, the
      recipient heart was 60 beats/min with acceleration up to 130 beats/min on
      exercise. A DDD pacemaker was implanted, the atrial lead was positioned in the
      right ventricule of the donor heart and the ventricular lead in the atrium of the
      recipient heart. Search for an optimal AV interval was evaluated by echo-Doppler
      and intraarterial pressure recordings. By increasing the AV interval from 125 to
      300 msec, the maximum aortic flow velocity of the recipient heart increased from
      1.0 to 1.2 m/sec. Left ventricular end-diastolic diameter remained unchanged,
      left ventricular end-systolic diameter decreased from 52 to 48 mm. Wall motion of
      the recipient left ventricle improved. At an AV interval of 125 msec there was
      alternate systolic contraction of both hearts, resulting in arterial pressure
      waves at a rate of 180/min. This did not relieve his symptoms and he complained
      further of headaches. At an AV interval of 300 msec contraction of the recipient
      heart just preceded that of the donor heart, resulting in arterial pressure waves
      at a rate of 90/min, normalization of the wave form, relief of symptoms, and
      improvement of exercise tolerance.

PMID- 1372723
TI  - Should a VVIR pacemaker increase the heart rate with standing?
AB  - To assess the usefulness of incorporating a posture sensor into a ventricular
      inhibited rate modulated pacemaker, the hemodynamic effects of increasing the
      ventricular pacing rate with standing were studied in 15 pacemaker dependent
      patients aged 55 +/- 3.5 years. In a randomized cross-over design, the pacing
      rate remained at 70 or was increased to 100 beats/min immediately prior to
      standing. Blood pressure was monitored continuously and forearm blood flow was
      measured by venous occlusion plethysmography. There was no difference in supine
      blood pressure (117 +/- 4/63 +/- 3 compared to 118 +/- 5/64 +/- 4 mmHg) or
      forearm blood flow (2.88 +/- 0.36 vs 2.94 +/- 0.32 mL/100 mL/min) before the 70
      or 100 pacing rate intervention. With standing, blood pressure fell to an
      equivalent degree at the two pacing rates (fall in mean blood pressure at 70
      beats/min 6 +/- 4 and at 100 beats/min 8 +/- 2 mmHg, P = 0.7). After 1 minute of
      standing differences in blood pressure were similar, but after 2.5 minutes of
      standing the increase in mean blood pressure was less at 70 than at 100 beats/min
      (increase from control 28 +/- 2 compared to 36 +/- 3 mmHg, P = 0.002). Forearm
      blood flow decreased after standing for 1 and 2.5 minutes but there was no
      difference between the 70 and 100 pacing rates (fall in forearm blood flow at 2.5
      minutes 0.50 +/- 0.24 and 0.59 +/- 0.25 mL/100 mL/cm2).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1372725
TI  - Longevity in patients with high degree atrioventricular block paced in the atrial
      synchronous or the fixed rate ventricular inhibited mode.
AB  - Survival in patients paced for high degree AV block has been demonstrated to be
      influenced by underlying cardiac disease in particular congestive heart failure.
      One previous study has suggested that dual chamber pacing may improve the vital
      prognosis for such patients. To investigate this, 74 patients treated with rate
      adaptive atrial synchronous (VDD) and 74 patients treated with VVI pacemakers for
      high degree AV block, were retrospectively studied for a mean of 5.4 years by
      life-table analysis. The two groups had an equal distribution of age, sex, date
      of pacemaker implantation, and concomitant cardiovascular diseases. Total
      mortality and estimated survival did not differ between the two groups. The
      estimated survival in the VDD group at 1, 3, and 5 years for patients without and
      with congestive heart failure was 94%, 86% and 78%, and 92%, 83% and 72%,
      respectively. In the VVI group the corresponding values were 95%, 90%, and 83%
      for patients without congestive heart failure and 82%, 64%, and 47% for those
      with congestive heart failure (P = 0.008). Compared to the expected survival rate
      of the general Swedish population, only the VVI group with congestive heart
      failure, had an excess mortality (P = 0.007). Patients with high degree AV block
      have a fairly normal vital prognosis irrespective of pacing mode. The prognosis
      for patients with congestive heart failure was negatively affected by VVI pacing.
      Thus, for patients with congestive heart failure the choice of pacing mode is of
      vital importance, whereas for patients without congestive heart failure, other
      factors such as feeling of well-being and exercise capacity should decide the
      final choice of pacing mode.

PMID- 1372726
TI  - Effect of bilateral stellectomy on electrical instability of the atrium in the
      dog with hypokalemia.
AB  - To investigate the effect of sympathetic nerve activity on electrical instability
      of the atrium in the presence of hypokalemia, open chest electrophysiological
      study was performed before and after bilateral stellectomy (BS) in 15 dogs with
      hypokalemia (hypokalemia group) and in 15 dogs with normokalemia (control group).
      Hypokalemia was created by infusion of 5.0 g/kg of polystyrene sulfonic acid
      calcium into the colon. Serum level of potassium was significantly lower in the
      hypokalemia group (2.94 +/- 0.52 mEq/L) than in the control group (4.86 +/- 0.51
      mEq/L, P less than 0.01) before BS. There was no significant change in serum
      level of potassium in the two groups after BS. Incidence of electrically induced
      atrial fibrillation (AF) was significantly higher in the hypokalemia group (80%)
      than in the control group (13%, P less than 0.001) before BS. It was
      significantly reduced in the hypokalemia group (40%, P less than 0.05), but not
      in the control group (6%) after BS. Dispersion of effective refractory period of
      the atrium (delta ERP) was significantly greater in the hypokalemia group (26.1
      +/- 2.8 msec) than in the control group (22.0 +/- 3.3 msec, P less than 0.005)
      before BS. It was significantly decreased to 23.1 +/- 3.2 msec in the hypokalemia
      group (P less than 0.001) and to 20.6 +/- 2.5 msec in the control group (P less
      than 0.01) after BS. Maximum conduction delay in the atrium (MaxCD) was 36.1 +/-
      3.5 msec before and 36.2 +/- 4.1 msec after BS in the hypokalemia group and 31.1
      +/- 4.2 msec before and 32.3 +/- 4.9 msec after BS in the control group. There
      was a significant difference in MaxCD between the two groups before BS. Atrial
      fibrillation threshold (AFT) was significantly lower in the hypokalemia group
      (3.9 +/- 0.7 mA) than in the control group (13.8 +/- 3.1 mA, P less than 0.001)
      before BS. It was significantly increased both in the hypokalemia group (6.5 +/-
      1.3 mA, P less than 0.001) and in the control group (15.0 +/- 2.7 mA, P less than
      0.005) after BS. It is concluded that sympathetic nerve activity may play some
      role in the increase in electrical instability of the atrium in the presence of
      hypokalemia.

PMID- 1372727
TI  - Results of electrophysiological testing and long-term follow-up in patients
      sustaining cardiac arrest only while receiving type IA antiarrhythmic agents.
AB  - Therapeutic management of patients sustaining a cardiac arrest while receiving
      antiarrhythmic agents can be difficult since the role of the drug in possibly
      facilitating the arrhythmia is often difficult to define. To determine if the
      response to programmed stimulation could give insight into which patients may
      have experienced a drug-induced cardiac arrest, we studied 29 patients (61 +/- 9
      years) with no prior history of sustained ventricular tachyarrhythmias (VT) who
      suffered a cardiac arrest only while receiving type Ia antiarrhythmic agents.
      Patients with documented myocardial infarction, acute ischemia, electrolyte
      abnormalities, or torsade de pointes were excluded from the study. Twenty-four
      patients had coronary artery disease with prior myocardial infarction (ejection
      fraction 28% +/- 9%) and five patients had idiopathic dilated cardiomyopathy
      (ejection fraction 31% +/- 6%). During baseline electrophysiological testing, 19
      patients (66%) had inducible sustained ventricular arrhythmias: uniform VT, n =
      14 (group I), polymorphic VT or ventricular fibrillation, n = 5 (group II). Ten
      patients (group III) had no inducible sustained ventricular arrhythmias. To
      determine if rechallenge with a type Ia agent could facilitate induction of a
      sustained ventricular arrhythmia in group III, eight patients underwent ten
      electrophysiological studies during therapy with either procainamide or
      quinidine. Only two patients developed sustained VT in response to programmed
      stimulation. Patients in groups I and II received therapy guided by
      electrophysiological testing, including antiarrhythmic agents alone (n = 8),
      subendocardial resection (n = 4), or an implantable cardioverter defibrillator (n
      = 7). Patients in group III received antiarrhythmic agents empirically (n = 3),
      or for treatment of atrial tachyarrhythmias (n = 2) or nonsustained VT (n = 1).
      In addition, four patients in group III received an implantable cardioverter
      defibrillator. During a mean follow-up of 28 +/- 27 months (range: 1 day-84
      months) 13 patients died suddenly or received a defibrillator shock preceded by
      syncope or presyncope: group I: n = 5; group II: n = 2; group III: n = 6. IN
      CONCLUSION: (1) most patients sustaining a cardiac arrest only in the presence of
      type Ia antiarrhythmic agents have inducible sustained VT in the absence of
      antiarrhythmic agents, and (2) the risk of recurrent VT persists in patients
      without inducible sustained arrhythmias in the drug-free state, regardless of
      whether they manifest inducible arrhythmias after rechallenge with a type Ia
      agent.

PMID- 1372724
TI  - Reproducibility of successful drug trials in patients with inducible sustained
      ventricular tachycardia.
AB  - Patients whose inducible sustained ventricular tachycardia is suppressed during
      serial electrophysiological testing have a small but gradually increasing
      actuarial incidence of recurrent arrhythmias despite therapy with the
      "successful" drug. In an effort to improve the predictive value of a drug
      response, in 1990 we began to require that our full stimulation protocol be
      repeated successfully several times before considering a drug to be effective. In
      23 consecutive patients who had inducible sustained ventricular tachycardia which
      was suppressed by at least one drug during invasive serial drug testing using a
      standard stimulation protocol, the identical stimulation protocol was performed
      six times during therapy with the initially successful drug (three trials on Day
      1 and three trials on Day 2). Repeat trials were completed (i.e., either all six
      trials were successfully finished or sustained tachycardia was induced) for 29
      initially successful drugs in these 23 patients. With 18 of these 29 initially
      successful drugs (62%), sustained ventricular tachycardia was eventually induced
      during repeat trials. The eventual drug failures could not be correlated with
      specific drugs tested, subtherapeutic or falling serum drug levels, marked
      fluctuations in autonomic tone, or changes in anatomic substrate. The proportion
      of patients failing each repeat trial was relatively constant: 4/29 (14%) failed
      Trial 2, 2/25 (8%) failed Trial 3, 7/23 (30%) failed Trial 4, 2/16 (13%) failed
      Trial 5, and 3/14 (21%) failed Trial 6. The increase in the cumulative incidence
      of drug failure during repeat trials was nearly linear. Inducibility of
      ventricular tachycardia appears to be a probability function; a successful drug
      study should not be regarded as an absolute phenomenon.

PMID- 1372728
TI  - Clinical experience with an activity sensing DDDR pacemaker using an
      accelerometer sensor.
AB  - The rate adaptive characteristics and pacemaker mediated tachycardia protection
      algorithm of an accelerometer based DDDR pacemaker were evaluated in 11 patients
      with bradycardia (seven atrioventricular block, four sick sinus syndrome). Rate
      adaptive programming was effected by collecting the acceleration level during a 3
      minute moderate exercise ("tailoring" of sensor). In comparison with an
      externally attached piezoelectric sensor, the accelerometer sensor showed lower
      rate changes during external tapping of the pacemaker (16 +/- 3 vs 29 +/- 4 ppm,
      P less than 0.02) and applied direct pressure (1 +/- 1 vs 40 +/- 3 beats/min, P
      less than 0.001) on the pacemaker. At nominal setting, the accelerometer sensor
      showed improved rate stability and higher rate response to jogging and standing,
      although responses to other daily activities and treadmill exercise were similar.
      Apart from changing the rate responsive slope, rate response could be improved by
      repeat "tailoring" of the sensor at a lower exercise level, resulting in better
      overall rate response characteristics. The ability of the rate monitoring
      software to collect acceleration levels for an activity and profile the projected
      rate response at different rate responsive settings allowed programming to be
      effected with the minimum amount of exercise testing. The pacemaker also
      discriminated atrial tachyarrhythmias from normal sinus response using the sensor
      to judge the appropriateness of the atrial rate, which correctly identified and
      prevented rapid ventricular tracking in two patients during atrial
      flutter/fibrillation.

PMID- 1372729
TI  - Effect on ventricular performance of direct current electrical shock for catheter
      ablation of the atrioventricular junction.
AB  - In ten patients undergoing catheter ablation of the atrioventricular junction
      (CAVJ) because of therapy refractoriness of supraventricular arrhythmias, the
      effect of repeated high energy direct current (DC) shock on left ventricular
      function has been investigated. End-systolic pressure-volume relation (ESPVR) and
      the positive first derivative of ventricular pressure (dP/dt) have been used as
      indices of left ventricular systolic function, while the time constant of
      isovolumic pressure decay, the diastolic stiffness, and the negative dP/dt
      represented the diastolic function parameters, respectively. Each patient
      received at least two and no more than three DC shocks for successful CAVJ, with
      an energy of 360 joules. Significant acute reduction of both systolic and
      diastolic function was noted after each DC shock, with a slow partial recovery of
      both phases. The recovery process involved the systolic phase earlier and more
      completely than the diastolic one. The alterations observed could not be
      predicted from preablation values, but were significantly related to cumulative
      energy dose index for body weight. In conclusion, repeated high energy DC shocks
      acutely, but reversibly, impair left ventricular function; in addition, the
      ventricular function reduction is primarily related to the total ablation energy
      indexed for body weight.

PMID- 1372730
TI  - Transesophageal atrial sensing for temporary VDD pacing.

PMID- 1372731
TI  - Transesophageal pacing.

PMID- 1372733
TI  - Prenatal identification of small mosaic markers of different chromosomal origins.
AB  - In situ hybridization using a series of alphoid DNA probes has demonstrated the
      origin of two small accessory mosaic marker chromosomes ascertained from 1079
      amniocenteses. These markers appeared to be de novo, derived from acrocentric
      chromosomes, and identical by traditional cytogenetic staining (G, Q, C, AgNOR,
      Hoechst-distamycin). Molecular characterization showed that one marker had
      originated from chromosome 14, the other from chromosome 22. Clinical outcome in
      both cases was normal.

PMID- 1372735
TI  - Characterization of the cytokeratins of human colonic, pancreatic, and gastric
      adenocarcinoma cell lines.
AB  - Cytokeratin-type intermediate filaments are a polygenic family of insoluble
      proteins that vary according to cell of origin and have been proposed as
      potentially useful markers of differentiation in epithelial malignancies. Because
      gastrointestinal malignancies resemble each other in their expression of many
      soluble antigens, we compared the cytokeratins of seven colonic, three gastric,
      six pancreatic, and one duodenal carcinoma cell lines, and one colon villous
      adenoma cell line. Cytokeratins were characterized by one- and two-dimensional
      gel electrophoresis, immunoblotting, and immunocytochemistry. These cell lines
      expressed combinations of cytokeratins 7, 8, 18, and 19, which are typical of the
      "simple" epithelial pattern found in normal ductal and glandular tissues of the
      gastrointestinal tract. However, pancreatic carcinoma cell lines expressed
      additional cytokeratins that are normally found in stratified squamous epithelium
      and epidermoid (squamous cell) carcinomas. These additional cytokeratins
      consisted of cytokeratin 16 in all six cell lines and cytokeratins 4, 13, and 16
      in one cell line. These results suggest that cytokeratin patterns represent
      stable markers that may aid in distinguishing gastrointestinal malignancies.

PMID- 1372734
TI  - Amniotic fluid levels of human chorionic gonadotropin and its alpha and beta
      subunits in second-trimester chromosomally abnormal pregnancies.
AB  - Amniotic fluid from 135 pregnancies was assayed for human chorionic gonadotropin
      (hCG) and its free alpha (ahCG) and free beta (bhCG) subunits. Forty-six
      chromosomally abnormal pregnancies between 14 and 20 weeks' gestation were
      matched with 89 chromosomally normal samples. Compared with controls, trisomy 21
      pregnancies exhibited significantly elevated levels of all three peptides,
      whereas trisomy 18 gestations gave rise only to significant elevation of ahCG.
      Female fetuses in both the trisomy 21 and trisomy 18 pregnancies provided
      significantly elevated levels of hCG and bhCG compared to their male
      counterparts. On converting the values to multiples of the median, it was
      determined that 6 of 7 trisomy 18 samples had abnormally elevated alpha/beta
      ratios, as did 6 of 21 Down's syndrome pregnancies. Further, 11 of 21 trisomy 21
      gestations had abnormal amniotic fluid hCG levels. Using only ahCG, bhCG and
      their ratio, a 61 per cent sensitivity was found for these trisomies, with a 96
      per cent specificity.

PMID- 1372732
TI  - The influence of sucrose, dextran, and hydroxypropyl-beta-cyclodextrin as
      lyoprotectants for a freeze-dried mouse IgG2a monoclonal antibody (MN12).
AB  - The influence of lyophilization on the stability of a monoclonal antibody (MN12)
      was investigated. MN12 was freeze-dried in different formulations [without
      lyoprotectant or in the presence of sucrose, dextran, or hydroxypropyl-beta
      cyclodextrin (HP beta CD)] and under varying conditions (with or without
      secondary drying). Subsequently, the monoclonal antibody was stored for 18 or 32
      days at various temperatures (4, 37, or 56 degrees C). For comparison, solutions
      of MN12 were stored under the same conditions. Regardless of the lyoprotectant
      used, precipitation and a concomitant reduction of the antigen-binding capacity
      by about 10% were observed upon reconstitution of lyophilized MN12. HP beta CD
      proved to be the most effective stabilizer to prevent degradation of lyophilized
      MN12 during storage. Compared with MN12 solutions, HP beta CD-containing
      lyophilized MN12 cakes were more resistant to heat-induced charge alterations and
      loss of antigen-binding capacity.

PMID- 1372737
TI  - Detection of occult metastases in pancreatic adenocarcinoma with anticytokeratin
      antibody.
AB  - Fifty-six lymph nodes excised from 11 patients with pancreatic adenocarcinoma
      were studied for evidence of metastasis by standard light microscopy and
      immunohistochemistry using an anticytokeratin monoclonal antibody. Eight of 56
      nodes contained metastatic carcinoma as demonstrated by conventional techniques.
      By immunohistochemistry, positive-staining cells were easily identified. In 10 of
      56 nodes, the positive staining was accompanied by cytologic atypia, changes
      consistent with malignancy. In seven additional nodes, positive-staining cells
      were present, but cytologic atypia was lacking. The use of immunohistochemistry
      facilitated recognition of malignant cells and raised questions that single-cell
      metastasis may be present. Positive staining for cytokeratin should prompt a
      close examination of cells to determine if morphologic features of malignancy are
      present.

PMID- 1372736
TI  - Expression of elongation factor-1 gamma-related sequence in human pancreatic
      cancer.
AB  - A cDNA clone designated pPDC-1 was isolated from a cDNA library prepared against
      poly(A+)RNA isolated from the human pancreatic adenocarcinoma cell line, Capan-2.
      The cDNA corresponds to a 1.7-kilobase mRNA that is expressed at higher levels in
      seven of nine pancreatic tumors than in their corresponding normal tissues. It is
      also expressed in normal human kidney, intestine, pancreas, stomach, placenta,
      lung, brain, spleen, and liver. A computer search of the Intelligenetics System
      of all available nucleotide sequences revealed a 60% homology between the
      nucleotide sequence of the pPDC-1 cDNA and that of elongation factor-1 gamma from
      Artemia. The deduced amino acid sequence shared 53% identity with the amino acid
      sequence for the Artemia elongation factor-1 gamma.

PMID- 1372739
TI  - Effects of FK506 on exocrine pancreas in rats.
AB  - The efficacy of FK506 on exocrine pancreas was studied in rats. Male Sprague
      Dawley rats (230-250 g) received an i.m. daily injection of FK506 (0.1, 0.5, or
      5.0 mg/kg), cyclosporine (CS; 25 mg/kg), or saline for 2 weeks. Isolated
      dispersed pancreatic acini were prepared from rats, and enzyme content of the
      cells and secretory response to cholecystokinin (CCK) were determined. Amylase
      and trypsin contents were increased in a dose-related manner by FK506 (p less
      than 0.01) and by CS at 25 mg/kg (p less than 0.01). The release of amylase in
      response to CCK was reduced by FK506 in a dose-related manner (p less than 0.01)
      and by CS at 25 mg/kg (p less than 0.01). Histologic examination showed that
      treatment of rats with FK506 at 0.1 mg/kg did not affect morphology of the acinar
      cells. FK506 at 0.5 mg/kg induced a minimal number of small vacuoles in cytoplasm
      of acinar cells and FK506 at 5.0 mg/kg, and CS at 25 mg/kg induced numerous
      cytoplasmic vacuoles and pyknotic nuclei. Increased enzyme storage and suppressed
      responsiveness of amylase release may have an association with the histologic
      changes. Therefore, the results of this study suggest that FK506, even when used
      in a low dose, may have adverse effects on the exocrine pancreas. Understanding
      of the mechanism of action of FK506 on pancreas will provide essential basic
      information that will allow transplant practitioners to more fully explore the
      benefits of this drug.

PMID- 1372738
TI  - Changes in peptidergic innervation in chronic pancreatitis.
AB  - We sought to identify characteristics of peptidergic innervation that altered in
      patients with chronic pancreatitis. Pancreatic tissue removed from patients with
      chronic pancreatitis was analyzed by immunohistochemistry using antisera against
      neuropeptide Y, tyrosine hydroxylase, vasoactive intestinal polypeptide, peptide
      histidine isoleucine, calcitonin gene-related peptide, and substance P,
      respectively. In accordance with recent findings, the number and diameter of
      intralobular and interlobular nerve bundles were found to be increased as
      compared with control pancreas from organ donors. The striking change in the
      peptidergic innervation pattern in chronic pancreatitis concerned these altered
      nerves. It consisted of an intensification of the immunostaining for calcitonin
      gene-related peptide and substance P in numerous fibers contained in these
      nerves. Adjacent sections showed that immunoreactive substance P and
      immunoreactive calcitonin gene-related peptide coexisted in these fibers. Because
      both of these peptides are generally regarded as pain transmitter candidates, our
      findings provide further evidence that changes in pancreatic nerves themselves
      might be responsible for the long-lasting pain syndrome in chronic pancreatitis.

PMID- 1372740
TI  - Reduced pancreatic content of the inhibitory neurotransmitter galanin in
      genetically obese, hyperinsulinemic mice.
AB  - Because abnormalities of the autonomic nervous system have been described in
      several animal models of obesity, and because galanin has been proposed to be a
      sympathetic neurotransmitter in the endocrine pancreas, we hypothesized that the
      hyperinsulinemia observed in genetically obese (ob/ob) mice may result either
      from defective ability of galanin to inhibit insulin release or from a reduced
      degree of pancreatic galaninergic innervation. To address these possibilities, we
      examined the effect of exogenous galanin on immunoreactive insulin (IRI) levels
      in ob/ob mice and compared the pancreatic content of galaninlike immunoreactivity
      (GLIR) in ob/ob mice with that in lean littermates. Intravenous administration of
      synthetic porcine galanin significantly reduced basal IRI levels in ob/ob mice,
      suggesting that a defect in galanin action is unlikely to account for the
      hyperinsulinemia in this model. In contrast, reduced pancreatic galaninergic
      innervation was supported by findings that pancreatic content of GLIR in ob/ob
      mice was less than 10% of that in age- and sex-matched lean littermates. The
      reduction of pancreatic GLIR in ob/ob mice appeared organ specific; no such
      reduction was observed in adrenal GLIR content when comparing obese and lean
      mice. In addition, the relationship between pancreatic GLIR content and plasma
      IRI levels was examined in groups of obese and lean mice. It was found in young
      females, young males, and older mice of mixed sex that there was a significant
      negative correlation between pancreatic GLIR and plasma IRI in lean mice, whereas
      no such correlation was observed in obese mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372742
TI  - Renal argininosuccinate synthetase: purification, immunohistochemical
      localization, and elastin-binding property.
AB  - Several proteins interact with elastin, an essential extracellular matrix
      element. We describe here an additional elastin-binding protein from the porcine
      kidney. This protein was extractable with an isotonic buffer, and was purified by
      a rapid and simple procedure employing its characteristic properties: high
      affinity for red A-agarose and spontaneous formation of cryoprecipitate.
      Immunohistochemical studies using antibody against the purified protein
      demonstrated its localization in the cytoplasm of proximal tubules of the normal
      rat kidney. On Western blotting using the antibody, an immunoreactive protein was
      detected in the liver as well as in the kidney. On the basis of the partial amino
      acid sequences of the purified protein, it was identified as argininosuccinate
      synthetase. Some biochemical properties of the protein were different from the
      data reporting a hepatic form of argininosuccinate synthetase, a key enzyme in
      the urea cycle in the liver. These results suggest that the elastin-binding
      property of a renal form of the enzyme may be related to a tissue-specific
      function in the kidney.

PMID- 1372741
TI  - On the helix sense of gramicidin A single channels.
AB  - In order to resolve whether gramicidin A channels are formed by right- or left
      handed beta-helices, we synthesized an optically reversed (or mirror image)
      analogue of gramicidin A, called gramicidin A-, to test whether it forms channels
      that have the same handedness as channels formed by gramicidin M- (F. Heitz et
      al., Biophys. J. 40:87-89, 1982). In gramicidin M- the four tryptophan residues
      have been replaced with phenylalanine, and the circular dichroism (CD) spectrum
      therefore reflects almost exclusively contributions from the polypeptide
      backbone. The CD spectrum of gramicidin M- in dimyristoylphosphatidylcholine
      vesicles is consistent with a left-handed helical backbone folding motif (F.
      Heitz et al., Biophys. Chem. 24:149-160, 1986), and the CD spectra of gramicidins
      A and A- are essentially mirror images of each other. Based on hybrid channel
      experiments, gramicidin A- and M- channels are structurally equivalent, while
      gramicidin A and A- channels are nonequivalent, being of opposite helix sense.
      Gramicidin A- channels are therefore left-handed, and natural gramicidin A
      channels in phospholipid bilayers are right-handed beta 6.3-helical dimers.

PMID- 1372744
TI  - Zonal changes of guanidine 3', 5'-cyclic monophosphate related to endothelium
      derived relaxing factor in dog renal medulla.
AB  - This study was undertaken to determine the basal and the stimulated profiles of
      endothelium-derived relaxing factor (EDRF) production along the cortical
      medullary axis of the dog kidney. To this end, slices (0.5 mm thick) were
      obtained from six zones equally spaced along the cortical medullary axis. Zone 1
      included the medullary crest, while zones 2 and 3 included the inner medulla,
      zone 4 the outer medulla, zones 5 and 6 the the middle and superficial cortex,
      respectively. The guanidine 3', 5'-cyclic monophosphate (cGMP) content (an index
      of EDRF production) was determined by radioimmunoassay under basal conditions and
      after acetylcholine (10(-5) M), bradykinin (10(-5) M) and SIN-1 (10(-4) M)
      stimulation. Under basal and stimulated conditions, the cGMP concentrations were
      highest in the midinner medulla and decreased progressively to lowest
      concentration in the cortex. These responses were inhibited by NG-monomethyl-L
      arginine (LNMMA), a specific antagonist of EDRF synthesis. In contrast, LNMMA did
      not alter the stimulation of cGMP produced by SIN-1 (10(-4) M) an endothelium
      independent vasodilator. This particular localization of EDRF-mediated
      stimulation on the midinner medulla may have a specific role in the regulation of
      sodium tubular reabsorption.

PMID- 1372743
TI  - Characterization of renal Na-K-ATPase gene expression by in situ hybridization.
AB  - Na-K-ATPase is a heterodimer of alpha- and beta-subunits often referred to as the
      'sodium pump' responsible for the maintenance of cell volume and electric
      potential across cell membranes. In the present study we have used antisense RNA
      probes to localize these subunits in the rat kidney by in situ hybridization.
      alpha 1-Subunit and beta-subunit gene expression are highest in cortical distal
      convoluted tubules, and the thick ascending limb of the loops of Henle; high in
      some proximal convoluted tubules, and low in the collecting ducts and blood
      vessels. Expression of the alpha 11 and alpha 111 isoforms is very low or absent
      throughout the kidney. These results confirm and extend studies of Na-K-ATPase
      enzyme activity levels and immunocytochemical localization in the kidney.

PMID- 1372745
TI  - Specific binding site for pro atrial natriuretic factors 1-30, 31-67, and 99-126
      on distal nephrons, proximal tubules, renal cortical and medullary membranes.
AB  - Two peptides with natriuretic and diuretic properties consisting of amino acids
      (a.a.) 1-30 and 31-67 of the 98 a.a. N-terminal end of the prohormone of atrial
      natriuretic factor (proANF), which normally circulates in humans and animals,
      were investigated to determine if they have specific binding sites on distal
      nephrons, proximal tubules, renal cortical and medullary membranes. Competitive
      binding experiments revealed that proANFs 1-30, 31-67, and 99-126 (i.e., C
      terminus; ANF) each had specific and separate binding sites. The dissociation
      constants (Kd) for proANFs 1-30, 31-67, and 99-126 binding to renal cortical
      membranes were similar at 9.8, 5.1, and 4.7 nM, respectively. In renal medullary
      membranes, on the other hand, proANF1-30 (Kd = 3.7 nM) and proANF31-67 (Kd = 2.9
      nM) had a 10-fold higher binding affinity than ANF (Kd = 56 nM). All three
      peptides had very weak binding to proximal tubules with the respective Kds for
      proANF1-30, proANF31-67, and ANF of 892, 789, and 550 nM indicating a 50- to 100
      fold less affinity for their binding sites in proximal tubules than in distal
      nephrons (Kds of 4.9, 5.3, and 11 nM, respectively). Each peptide bound to the
      respective kidney membranes or tubules between 10(-8) and 10(-11) M but could
      only bind to the other peptides' receptors at concentrations of 10(-6) and 10(-7)
      M. Neither insulin, growth hormone, nor adrenocorticotrophic hormone
      competitively inhibited the binding of proANF 1-30, proANF 31-67 or ANF. These
      results suggest that proANF 1-30 and proANF31-67 do not work through the ANF
      receptor but rather have their own separate and distinct receptors to mediate
      their diuretic and natriuretic effects in the kidney.

PMID- 1372746
TI  - Antigenic changes of the glomerular basement membrane after incorporation of
      hydroxyproline isomers.
AB  - We investigated antigenic changes of murine glomerular basement membrane (GBM)
      collagen type IV after oral feedings of 3-cis- or 4-cis-hydroxyproline. As shown
      by thin layer chromatography and gas chromatographic-mass spectrometric studies,
      3-cis- and 4-cis-hydroxyproline were incorporated into the GBM collagen instead
      of the normal trans isomer and led to a considerable reduction of the collagen
      antibody reactivity on indirect immunofluorescence, passive hemagglutination and
      radioimmunoassay when compared to GBM collagen of control animals. We speculate
      that antigen modification due to the incorporation of stereoisomers could serve
      as a model for basement membrane immunopathology.

PMID- 1372748
TI  - Brain-gut peptides and the renal hemodynamic response to an oral protein load: a
      study of gastrin, bombesin, and glucagon in man.
AB  - With the aim of disclosing a possibility for gastrin and bombesin to participate
      in the postprandial regulation of the renal hemodynamic response, 10 healthy
      males were studied before and after a meat meal (2 g/kg BW of proteins as cooked
      red meat). We evaluated the time course changes of glomerular filtration rate
      (GFR) renal plasma flow (RPF), and the plasma concentrations of gastrin,
      bombesin, glucagon, and total amino acids. After the meat meal a significant
      increase in GFR and RPF was seen, within 30 min, along with an increase in plasma
      gastrin and glucagon. Bombesin and amino acid concentrations increased at a later
      time. The data suggest but cannot demonstrate a causal role for gastrin and
      glucagon in the genesis of the hyperfiltration response to acute protein
      administration.

PMID- 1372752
TI  - New evidence found for a nuclear matrix.

PMID- 1372747
TI  - Renal handling of sodium after an oral protein load in adult humans.
AB  - This investigation was designed to study (1) renal sodium handling after an oral
      protein load and (2) its relationship to some known determinants of the
      hemodynamic response (glucagon, insulin, growth hormone, renin, aldosterone, and
      plasma amino acid concentration). To this end of group of 8 adult subjects was
      studied before (three 30-min clearances) and after a meat meal (MM; five 30-min
      clearances at 30, 60, 90, 120 and 180 min). The MM provided 2 g/kg BW of protein.
      Within 30 min from the MM an hyperfiltration response was seen, which was
      paralleled by a 2-fold increase in plasma alanine concentration while total
      plasma amino acid concentration was not different from the baseline values. The
      hemodynamic response was associated with a normally operating tubuloglomerular
      feedback mechanism independent of renin-aldosterone activity, but possibly
      associated with an early increase in plasma glucagon concentration and later on
      with a modest increase in postmeal plasma insuling concentration.

PMID- 1372749
TI  - Local immune response in the chicken Harderian gland to antigen given by
      different ocular routes.
AB  - The effectiveness of three ocular routes of antigen administration to produce a
      local immune response in the Harderian gland was studied. The routes were by
      eyedrop, injection into the ocular conjunctiva and injection into the nictitating
      membrane. The antigen was observed in the cytoplasm of macrophages located within
      the lymphoid tissue only after the injection into the nictitating membrane. The
      numbers of germinal centres and plaque forming cells found in the gland after
      injection into the nictitating membrane was higher than the numbers observed
      following the other two ocular applications. These findings indicate that the
      injection of the antigen into the nictitating membrane is the most effective
      ocular route for producing a local immune response in the Harderian gland.

PMID- 1372751
TI  - Hypoxic contraction of pre-stretched human pulmonary artery.
AB  - To clarify the mechanism of hypoxic pulmonary vasoconstriction in man, human
      pulmonary artery segments (2 mm O.D.) were suspended and changes in isometric
      force were measured. The arteries were contracted by hypoxia (PO2 43 +/- 2 Torr)
      developing a tension of 127 +/- 36 mg over the course of 15 min. This contraction
      was completely blocked by 10(-6) M L-isoproterenol, 10(-6) M nitroglycerin,
      partially blocked by 10(-8)-10(-6) M verapamil, unchanged by 10(-6) M
      phentolamine, 10(-6) M L-propranolol, 10(-6) M diphenhydramine, 10(-6) M
      guanethidine, 10(-7) M FPL 55712 and enhanced by 10(-6) M BAY K 8644, 10(-3) M
      procaine, 3 x 10(-6) M quinacrine, 10(-6) M indomethacin or 10(-6) M methylene
      blue. Removal of the endothelium significantly enhanced the magnitude of hypoxia
      induced contraction. These results suggest that the human pulmonary artery
      constricts in response to hypoxia, at least in part, through activation of the
      voltage-dependent Ca2+ channels and that neither alpha, beta, H1 receptors, the
      lipoxygenase pathway nor neural reflexes are involved. They also show that the
      endothelium is not required for hypoxic contraction and that its presence reduces
      sensitivity to hypoxia.

PMID- 1372750
TI  - Immunoglobulin classes synthesised by the chicken Harderian gland after local
      immunisation.
AB  - The immunoglobulin (Ig) levels in tears and sera were compared after antigen
      administration (salmonella O antigen) by eyedrop and injection into the
      nictitating membrane, to determine the Ig classes synthesised by the plasma cells
      in the chicken Harderian gland. Samples of tears and sera were collected from
      immunised and control birds between 24 hours and 24 days after the antigen or
      sterile saline was administered. Samples were assayed for IgA, IgG and IgM
      concentrations using radial immunodiffusion. It is suggested that most of the IgG
      found in tears after local immunisation has an extraglandular origin.

PMID- 1372753
TI  - A single amino acid that determines the sensitivity of progesterone receptors to
      RU486.
AB  - The progesterone analog RU486, an abortifacient, inhibits the action of
      progestins in humans but not in chickens or hamsters. Substitution of cysteine at
      position 575 by glycine in the hormone binding domain (HBD) of the chicken
      progesterone receptor (cPR) generated a cPR that binds RU486 and whose activity
      is antagonized by that compound. In fact, all receptors that bind RU486 have a
      glycine at the corresponding position. The hamster PR, like cPR, has a cysteine.
      Only glycine--not methionine or leucine--at position 575 allowed binding of RU486
      to cPR. Substitution of this glycine by cysteine in the human PR (hPR) abrogated
      binding of RU486 but not that of an agonist. The corresponding mutation in the
      human glucocorticoid receptor resulted in a loss of binding of both dexamethasone
      and RU486. Examination of a series of 11 beta-substituted steroids showed that
      antagonism is not an intrinsic property of an antihormone, because one hPR
      antagonist acted as an agonist for a mutated hPR. The positioning of an aromatic
      11 beta-substitution in the PR HBD appears to be critical for generating
      agonistic or antagonistic activity.

PMID- 1372754
TI  - Selection of intrinsic horizontal connections in the visual cortex by correlated
      neuronal activity.
AB  - In the visual cortex of the brain, long-ranging tangentially oriented axon
      collaterals interconnect regularly spaced clusters of cells. These connections
      develop after birth and attain their specificity by pruning. To test whether
      there is selective stabilization of connections between those cells that exhibit
      correlated activity, kittens were raised with artificially induced strabismus
      (eye deviation) to eliminate the correlation between signals from the two eyes.
      In area 17, cell clusters were driven almost exclusively from either the right or
      the left eye and tangential intracortical fibers preferentially connected cell
      groups activated by the same eye. Thus, circuit selection depends on visual
      experience, and the selection criterion is the correlation of activity.

PMID- 1372755
TI  - Inhibition of myeloid differentiation by the helix-loop-helix protein Id.
AB  - Id is a helix-loop-helix (HLH) protein that represses activity of several basic
      helix-loop-helix (bHLH) proteins involved in cell type--specific transcription
      and cell lineage commitment. The myeloid precursor cell line 32DC13(G) expressed
      Id messenger RNA, which was transiently decreased when cells were induced to
      terminally differentiate with granulocyte--colony-stimulating factor. Concomitant
      with the decrease of Id messenger RNA was the appearance in nuclear extracts of
      DNA binding proteins that recognized a canonical E-box motif, a DNA binding site
      for some bHLH proteins. Constitutive expression of an Id complementary DNA in
      32DC13(G) cells blocked their ability to differentiate and to induce E-box
      binding activity. These results suggest that Id and, hence, bHLH proteins
      function in the process of myeloid differentiation.

PMID- 1372756
TI  - Salvage therapy in recurrent testicular cancer.
AB  - Patients with testicular cancer who relapse after primary chemotherapy are still
      curable and should be treated aggressively with this goal in mind. These patients
      should receive a cisplatin-based regimen, usually including ifosfamide and either
      vinblastine or etoposide (depending upon prior exposure to drugs). As with first
      line therapy, chemotherapy should not be delayed because of blood counts alone.
      Because this patient population has a higher incidence of significant
      myelosuppression, the use of hematopoietic growth factors may be of value and is
      currently being investigated. Patients who achieve a CR after salvage
      chemotherapy can be followed as usual with monthly serum markers and chest x
      rays. For those patients who have a marker-negative partial remission, resection
      of all residual disease (if possible) is appropriate. If the surgical specimen
      contains only necrotic material or teratoma, then they should also be followed
      without further therapy. The appropriate approach for patients with residual
      carcinoma at the time of surgical resection is uncertain. The standard approach
      at Indiana University has been to give two more cycles of chemotherapy post
      operatively, however most of these patients will eventually relapse and require
      further treatment. Patients are currently being treated with oral etoposide for 3
      months after surgery in an attempt to improve long-term survival. Whether this
      approach will be of benefit remains to be seen. Patients who fail second-line
      chemotherapy should be considered for high-dose chemotherapy with autologous bone
      marrow rescue. Patients who do not normalize their serologic markers with first
      line chemotherapy or who relapse within 1 month after chemotherapy are truly
      platinum refractory and do poorly with standard-dose second line cisplatin-based
      chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372757
TI  - Current perspectives on the role of adjunctive surgery in combined modality
      treatment for patients with germ cell tumors.
AB  - The role of surgery in patients with advanced GCT after chemotherapy has evolved
      substantially in the era of combined modality therapy. In evaluating patients for
      surgery after chemotherapy, the clinician must consider carefully the histology
      (seminoma v NSGCT) of the primary as well as the extent of the residual disease.
      In patients with seminoma, the size of residual disease (greater than or equal to
      3 cm) permits selection of patients with a high incidence of residual malignancy.
      In contrast, criteria designed to select NSGCT patients in whom surgical
      intervention after chemotherapy can be avoided are associated with substantial
      error. A normal radiographic evaluation in patients with NSGCT does not indicate
      a negative pathology and the treating physician must consider the approximately
      20% risk of residual teratoma or carcinoma despite evidence of a radiographic CR.
      Continued research is needed to improve the sensitivity and specificity of case
      selection for patients requiring surgery after chemotherapy in order to limit the
      toxicity of curative therapy in this patient population.

PMID- 1372758
TI  - Treatment of "good risk" metastatic testicular cancer.

PMID- 1372759
TI  - Treatment of seminoma.

PMID- 1372760
TI  - Prognostic factors in metastatic disease.

PMID- 1372761
TI  - "Poor-risk" germ cell tumors: current progress and future directions.

PMID- 1372762
TI  - Interactions between cytokines and cytotoxic drugs: putative molecular mechanisms
      in experimental hematology and oncology.

PMID- 1372763
TI  - Hematopoietins in combination with 1-beta-D-arabinofuranosylcytosine: a possible
      strategy for improved treatment of myeloid disorders.
AB  - Inhibitors of DNA synthesis, such as 1-beta-D-arabinofuranosylcytosine, have been
      proven useful in the management of acute myelogenous leukemia. Despite
      significant improvement of response rates, long-term disease-free survival can be
      presently achieved only in a small percentage of patients. As S-phase--specific
      drugs, such as the inhibitors of DNA synthesis, only reach the cycling part of
      their target populations, dormant cells are left mainly unaffected. Their
      survival, however, is largely responsible for later disease relapse. This paper
      reports experiments that show that cell kinetic manipulations by hematopoietic
      growth factors may help to overcome the problem of cytokinetic and pharmacologic
      resistance. Hematopoietic growth factors synergize with inhibitors of DNA
      synthesis given at low doses to induce a more mature phenotype or to enhance
      leukemia cell kill when combined with high doses of DNA inhibitors. In addition,
      we present data to unravel several aspects of the molecular mechanism underlying
      this synergism.

PMID- 1372764
TI  - Antineoplastic activity of the combination of 5-fluorouracil and interferon:
      preclinical and clinical results.
AB  - Interferon (IFN) is capable of modulating the cytotoxic effects and clinical
      activity of the fluorinated pyrimidine, 5-fluorouracil (5-FU). This occurs in the
      absence of a demonstrable effect on immune function, suggesting that these
      effects occur at the biochemical level. Pharmacokinetic studies have also
      demonstrated that IFN can increase serum levels of 5-FU. The relative importance
      of these effects on enhancement of 5-FU activity remains to be investigated.

PMID- 1372765
TI  - Combined treatment of metastatic melanoma with interferons and cytotoxic drugs.
AB  - The treatment of disseminated melanoma with monotherapy and combined chemotherapy
      is still associated with rather low objective response rates and significant
      toxicity. Therefore, more effective substances and regimens with less toxicity
      are desired in the pharmacologic treatment of metastatic melanoma. The initial
      high expectations placed in systemic cancer treatment with interferons (IFNs)
      were not fulfilled, but IFN-alpha as a single substance revealed an objective
      response rate of 10% to 15% in melanoma patients. Clinical and experimental
      results suggest that the antitumoral activity of IFNs is mainly related to their
      antiproliferative effect, whereas immunomodulatory effects were not substantiated
      in clinical investigations. Results of in vitro trials showed that type-I IFNs
      may produce antagonistic effects combined with some agents (eg, cisplatin) and
      synergistic effects combined with others (eg, vindesine and BCNU). Clinical
      trials with combined IFN and cytostatic drug therapy were started a few years ago
      and have yielded promising initial results. Several studies with an entire number
      of more than 200 patients have already been performed to evaluate the combination
      of IFN-alpha and dacarbazine. This regimen was effective in over 50% of the
      patients, leading to complete or partial remissions in 27% and stabilization of
      the disease in an additional 28%. Toxicity is significant but still manageable,
      especially with a new generation of antiemetic drugs (serotonin receptor
      blockers). Several clinical trials performed so far did not find an improved
      efficacy by adding IFN-alpha to cisplatin or to vinblastine. The combination of
      IFN-alpha and vindesine seems to be more favorable and superior to the response
      rates of single agents and was well tolerated in an ongoing trial in our clinic.
      Recently, a new generation of multidrug combinations including IFN-alpha has been
      initiated and several reports with overall response rates greater than 50% have
      been published. In conclusion, combined regimens with IFN-alpha and different
      cytostatic drugs seem to be superior to treatments with cytostatic drugs alone
      and rather safe in disseminated melanoma. Additional combinations of IFNs and
      cytostatic drugs should be evaluated in future in vitro studies and in clinical
      trials.

PMID- 1372766
TI  - Treatment of myelodysplastic syndromes with cytokines and cytotoxic drugs.
AB  - Clinical trials with hematopoietic growth factors (granulocyte-macrophage colony
      stimulating factor [GM-CSF], granulocyte colony-stimulating factor [G-CSF],
      interleukin-3, erythropoietin] have been done in patients with myelodysplastic
      syndromes. Treatment with GM-CSF or G-CSF has resulted in an increase of
      neutrophil counts into the normal range in the vast majority of patients.
      Progression to acute leukemia does not appear to occur more frequently in the
      patients receiving GM-CSF or G-CSF. Increases in platelet counts and hemoglobin
      levels have been reported after treatment with interleukin-3 and erythropoietin,
      respectively, although the response is only seen in a minority of treated
      patients. Combination therapy with GM-CSF and low-dose cytosine arabinoside has
      been studied, but present data do not indicate an advantage over other treatment
      strategies. Cytogenetic and molecular genetic analyses demonstrate that both
      normal and malignant precursor cells are stimulated by cytokine therapy.

PMID- 1372767
TI  - Neural elements in human cervical intervertebral discs.
AB  - This study attempted to characterize neural elements within the human cervical
      intervertebral disc. Cervical intervertebral discs were obtained from four adult
      human subjects at autopsy. Discs were stained in bulk with gold chloride,
      sectioned, and viewed with the light microscope. Nerve fibers appeared to enter
      the disc in the posterolateral direction and course both parallel and
      perpendicular to the bundles of the anulus fibrosus. Nerves were seen throughout
      the anulus but were most numerous in the middle third of the disc. Receptors
      resembling Pacinian corpuscles and Golgi tendon organs were seen in the
      posterolateral region of the upper third of the disc. These results provide
      further evidence that human cervical intervertebral discs are supplied with both
      nerve fibers and mechanoreceptors.

PMID- 1372768
TI  - [The percutaneous-endocavitary irradiation of esophageal carcinomas].
AB  - In a prospective, nonrandomized study 43 patients with inoperable oesophageal
      carcinoma were treated with a combined therapy of external and intracavitary
      irradiation according to the Heidelberg protocol adjusted to tumor stage, general
      condition and age. The proportion of external beam to afterloading doses was
      2/3:1/3. The reference doses were between 50 and 75 Gy. Intracavitary
      radiotherapy was carried out with a HDR-afterloading device in single doses of 5
      Gy. In a median follow-up of 23 months 46% had a complete remission and 42% had a
      partial remission. Within ten months 17 patients (39.5%) showed local tumor
      progression or recurrence. Presently the estimated median survival time of the
      whole collective is eleven months. The median survival was significantly
      influenced by achievement of complete remission (17.7 months in comparison to 8.7
      months by missing complete remission). After completion of therapy 90% had
      sufficient oral nutrition. During long-term follow-up in 44% of the cases
      repeated measures had to be taken to eliminate initial or recurrent dysphagia.
      Almost all postradiogenic stenoses were caused by tumor progression. Radiogenic
      side-effects caused by HDR-afterloading boosts, exceeding the acceptance, were
      not found. The combined therapy reduces the period of hospitalisation and has the
      same palliative effects as an exclusively external radiotherapy.

PMID- 1372769
TI  - [Expertise on examination and treatment of children with developmental and
      behavior disorders].

PMID- 1372770
TI  - Soluble and nuclear type I and II androgen-binding sites in benign hyperplasia
      and cancer of the human prostate.
AB  - This paper presents an approach for the assessment of the androgen receptor (AR)
      status in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissues.
      Evaluation of AR was carried out in both soluble and nuclear fractions by a
      standard competition method, using tritiated mibolerone as radioligand. Based on
      our experience with breast and endometrial cancer, this approach focused on both
      type I (high affinity, low capacity) and type II (reduced affinity, higher
      capacity) binding sites, aiming mainly at establishing a putative "functional"
      receptor mechanism, i.e., the presence of type I AR in both cytosol and nucleus.
      Ancillary studies were carried out to exclude a potential overestimation of the
      AR content by interference with other steroid receptors, namely, progesterone
      (PgR) or glucocorticoid (GcR) receptors. Results showed that the interaction by
      PgR or GcR upon AR measurement was not relevant. The distribution of AR, namely
      the percent of positivity either in a single or in both cell compartments, was
      not significantly different in BPH (N = 32) or PCa (N = 24) tissues. For type I
      binding, the percent of positivity in both soluble and nuclear fractions (i.e.,
      the "functional" AR status) was very close to that observed for other endocrine
      related tumors, like breast cancer. Concentrations of type I AR appeared
      significantly higher in PCa than in BPH tissues; this was true for both soluble
      and nuclear fractions. In contrast, no significant difference was found in type
      II AR concentrations in either cell fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372771
TI  - Partial purification and characterization of a growth factor from human
      hyperplastic prostatic tissues.
AB  - A growth factor capable of stimulating DNA synthesis of Balb/c 3T3 cells was
      purified by heparin-Sepharose column chromatography about 1900-fold from the
      cytosol of human prostatic tissues obtained at autopsy or open prostatectomy.
      This growth factor bound to heparin-Sepharose in the presence of 0.5 mol/l NaCl
      and was eluted by 1.0-1.55 mol/l NaCl. Its molecular weight was estimated to be
      68,000 by SDS-polyacrylamide gel electrophoresis. The amino acid composition was
      determined and compared with the data of other growth factors, which revealed no
      striking conformity. Distribution of growth factor activity was investigated in
      mechanically separated prostatic tissues of benign prostatic hyperplasia. The
      separation scheme provided two fractions: the stromal fraction consisting mainly
      of fibroblasts, fibers and smooth muscle, and the epithelial fraction consisting
      of epithelial cells. The specific growth-stimulating activity in the stromal
      fraction was about 2-fold that in the epithelial fraction. Referred to the total
      activity of whole tissue, about 74% of the activity could be detected in the
      stromal fraction, while only about 5% was detectable in the epithelial fraction.
      This study demonstrates the existence of a growth factor in human benign
      hyperplastic prostatic tissues, showing a remarkable distribution of growth
      factor activity, which may play a role in the pathogenesis of benign prostatic
      hyperplasia.

PMID- 1372773
TI  - [Effect of TUR and transvesical prostatectomy on symptomatology and quality of
      life].
AB  - The influence of transurethral resection and transvesical prostatectomy on
      symptoms and quality of life in patients with benign prostatic hyperplasia was
      evaluated and compared in a prospective study. Two groups of 20 patients each
      were matched for preoperative symptoms, flow and residual urine. A detailed
      questionnaire was completed by the patients preoperatively and at various
      intervals postoperatively. In the patients' judgement both operations brought
      about a fast and significant improvement of their symptoms. Sexuality, erectile
      function and libido were not reduced. During the 6-month follow-up no significant
      differences was found between the two operative procedures in their effects on
      the parameters examined. Thus, the choice of operation can be based entirely on
      other parameters, such as prostate weight.

PMID- 1372772
TI  - Estrogenic action of commonly used fragrant agent citral induces prostatic
      hyperplasia.
AB  - A rat model for benign prostatic hyperplasia in man (BPH) was investigated.
      Citral treatment of male Copenhagen rats for 4 months via the transdermal route
      resulted in a marked hyperplasia of glandular epithelium and interglandular
      stroma in the ventral prostate. Despite the cellular hyperplasia there was not a
      significant increase in prostate weight. Investigations of the mechanism of
      action of citral showed that application of citral directly to the vagina in
      female, ovariectomized rats resulted in an increased proliferation of vaginal
      epithelium and a significant increase in the BrdUrd incorporation in vaginal
      epithelial cells, in short a similar effect to that of estrogen application. In
      an in vitro assay citral proved to inhibit estrogen binding to estrogen
      receptors, while no such inhibition was observed with testosterone for androgen
      receptors. These observations together with the estrogen implication in the BPH
      and the reported incidence of gynecomastia following exposure to geraniol, a
      precursor of citral, strongly suggest that the prostatic hyperplasia-inducing
      capacity of citral may be due to its estrogenic action.

PMID- 1372774
TI  - [Incidental prostatic cancer--"wait and see" or radical prostatectomy?].
AB  - In a comparative and retrospective study, outcome was examined in two groups of
      patients with incidental carcinoma of the prostate (stage T1a). In the 47
      patients in the first group the carcinoma was kept under observation for 2-10
      years without the administration of any treatment. During the mean follow-up of 5
      years, the disease progressed in 11 (23.4%) of these patients, and 4 of them
      died. The other group was made up of 20 patients who underwent radical
      prostatectomy. The clinical and pathological staging were quite different in this
      group than in the other: more advanced stages and higher grades were seen in 10
      patients, and the specimens taken from 6 were found not to contain any tumour.
      After a mean follow-up period of 4.5 years, all these 20 patients are alive with
      no evidence of disease. The management of patients with T1a tumour is still a
      problem. Observation only will be followed by progression in 23% of cases, while
      radical prostatectomy actually constitutes overtreatment in 30%. In conclusion,
      we prefer to perform prostatectomy in all patients with T1a carcinoma who are
      young and have a good life expectancy.

PMID- 1372775
TI  - [Solitary osseous metastasis in a patient with germ cell tumor--successful
      chemotherapy].
AB  - A 25-year-old patient with testicular teratoma (pathological stage I) relapsed
      with a solitary, symptomatic metastasis in the right humerus 8 months after
      unilateral orchiectomy and lymphadenectomy. Treatment consisted in three cycles
      of standard chemotherapy with etoposide, bleomycin and cisplatin (the last
      replaced by carboplatin in courses 2 and 3). No supplementary treatment proved
      necessary to achieve complete remission and complete physical rehabilitation.
      Only four cases of solitary bone metastasis of testicular germ cell tumors have
      been reported previously. The present case illustrates that, contrary to previous
      reports, symptomatic skeletal metastases of germ cell tumors can safely be
      treated with standard chemotherapy alone.

PMID- 1372776
TI  - [Hyperthermia and thermotherapy of the prostate--state and value].

PMID- 1372777
TI  - [New conservative therapeutic approaches in benign prostatic hyperplasia].
AB  - The efficacy of treatment for benign prostatic hyperplasia (BPH) is presently
      under critical consideration. In addition, various new therapeutic modalities are
      currently being evaluated. When medicamentous treatment is planned, in
      particular, the natural history of the disease must be carefully considered.
      Summarized data from several studies indicate that spontaneous improvement of
      symptoms may occur within 3-6 months, while in most cases deterioration takes a
      longer period of time. As intraprostatic urethral pressure depends on prostatic
      volume as well as on tone of the prostate smooth muscle, different medical
      treatment modalities seem reasonable. The dynamic component of the smooth muscle
      cells may be influenced by alpha-blockers. Administration of selective alpha 1
      blockers will be advantageous as these have fewer side effects. Prostate volume
      represents the static component, which can be influenced by hormone treatment.
      Androgen deprivation via surgical castration must now be regarded as of
      historical interest only. Antiandrogens or LH-RH analogues have undesirable side
      effects and are expensive, making such treatment unacceptable for routine use. 5
      alpha-Reductase inhibitors may emerge as a new treatment form allowing androgen
      suppression with a low rate of side effects. As it has been proposed that
      estrogens play an important role in the regulation of prostatic growth, aromatase
      inhibitors, which inhibit metabolization from androgens to estrogens, may receive
      special attention in the near future. Based on the theory that androgens may be
      of special importance for the epithelium, while estrogen action may be
      concentrated on the stroma, a combined treatment with inhibitors of 5 alpha
      reductase plus aromatase may be even more effective.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1372778
TI  - Differential diagnostic patterns of lung neuroendocrine tumours. A clinico
      pathological and immunohistochemical study of 122 cases.
AB  - A series of 3 tumourlets (TLs), 81 typical carcinoids (TCs), 14 atypical
      carcinoids (ACs) (well-differentiated neuroendocrine carcinomas, WDNCs) and 24
      small cell-intermediate cell carcinomas (SCC-ICCs) of the lung were studied.
      Histopathological features were correlated with amine and peptide hormone
      immunoreactivity and with clinical data. All types of tumours expressed general
      neuroendocrine (NE) markers: Grimelius positivity and chromogranins were detected
      more frequently in well-differentiated (TLs, TCs) than in less well
      differentiated tumours [ACs (WDNCs) and SCC-ICCs] whereas neuron specific enolase
      (NSE) was prominent in the latter tumours. TLs and peripheral TCs were benign,
      often showing a paraganglioid pattern and frequently expressing gastrin-releasing
      peptide (GRP), which is present in the peripheral airways of normal lung. Central
      TCs were associated with lymph node metastases in 8.5% of the cases, frequently
      had a trabecular architecture, often associated with human milk fat globule 2
      (HMFG2)-positive acinar and rosette-like structures, and were mainly
      immunostained for the alpha-subunit of human chorionic gonadotrophin (alpha-hCG)
      and serotonin. ACs (WDNCs) were associated with intrathoracic and/or
      extrathoracic metastases in 57.1% of the cases with a mortality rate of 35.7%.
      Their histological and cytological features were intermediate between those of
      TCs and SCC-ICCs. ACs (WDNCs) expressed serotonin and alpha-hCG less frequently
      than TCs. All SCC-ICCs were surgically treated and displayed a mortality rate of
      91.6% with a mean survival of 10.2 months after operation. These tumours were
      characterized by high expression of HMFG2 and NSE, while the expression of both
      orthotopic (serotonin, GRP) and ectopic (ACTH) specific NE substances was very
      low. Since all TCs (either central or peripheral) had a favourable outcome, while
      about 36% of ACs (WDNCs) were fatal, the latter seem more appropriately
      designated "well-differentiated NE carcinomas". The differential diagnosis
      between different NE tumours of the lung is important and is mainly based on
      morphology. Both panendocrine and specific immunohistochemical markers are
      helpful in distinguishing the less aggressive, mostly benign varieties from the
      more malignant varieties.

PMID- 1372779
TI  - Granular cell tumour of the breast.
AB  - Eight cases of benign granular cell tumour of the breast are reported. Seven
      patients were women and one was male. The age at the time of the excision ranged
      from 17 to 73 (average 40.1) years. All tumours were positive for S-100 protein
      and negative for keratin, myoglobin and gross cystic disease fluid protein. In
      two cases ultrastructural studies revealed findings identical to those in the
      previously reported cases of granular cell tumours. None of these cases were
      diagnosed preoperatively. In six cases the clinical and mammographic findings,
      and in one case the frozen section, led to an erroneous diagnosis of malignancy.
      The clinico-pathological features of the cases are delineated in order to draw
      attention to a benign condition which closely simulates malignancy.

PMID- 1372780
TI  - Histological reactivity of a monoclonal antibody against rat colon cancer cells
      on human and rat normal gut and colonic tumours.
AB  - A monoclonal antibody, F11C, was raised against rat colon cancer cells. Its
      immunoreactivity on normal human and rat gut as well as human and rat colonic
      tumours was studied by the avidin-biotin-peroxidase complex technique. In both
      normal rat and human gastrointestinal tract, F11C stained surface epithelial
      cells from the fundus to distal colon, mainly as supranuclear vesicles. These
      vesicles appeared to be part of the Golgi apparatus on electron microscopy with
      immunogold labelling. Twenty primary rat colon tumours and 28 of 43 human colon
      tumours were also stained, with a heterogeneous pattern but much more strongly
      than the normal colonic mucosa. Biochemical purification suggested that in rat
      tumours F11C epitope was carried by a high molecular weight glycoprotein.
      Absorption experiments with synthetic oligosaccharides showed that F11C
      monoclonal antibody reacted with blood group A-related oligosaccharides.
      Nevertheless, F11C reactivity on human tissues was not related to the individual
      ABO or Lewis phenotype.

PMID- 1372781
TI  - [Itching following therapy with hydroxyethyl starch (HES) in otoneurological
      diseases].
AB  - It is generally assumed, that a disturbance of microcirculation is the common
      pathogenetic end factor in various cochleovestibular disorders of different
      etiology. Therefore improvement of microcirculation is an important therapeutic
      goal. Several studies demonstrated, that hydroxyethylstarch (HES) has better
      haemorheological effects than Dextran and less side effects. For this reason we
      have changed the therapy with Dextran since 1987 to hydroxyethylstarch in several
      oto-neurological disorders (as sudden hearing loss, neuronopathia vestibularis,
      idiopathic facial palsy). As after the therapy with HES--generally after
      dismissal from the ENT-department--some patients complained of general pruritus,
      so we performed a retrospective study with a standardized interview-protocol. Of
      481 treated patients we investigated 237 (49%): of 149 patients treated with HES
      200/0.5, 43 patients (28.8%) complained of pruritus; from 88 patients treated
      with Dextran 40, only 5 patients (5.7%) reported pruritus. The difference is
      significant (p less than 0.0001). In nearly half of the patients (more than 40%)
      the pruritus started in normal skin 1 to 3 weeks after the HES-therapy and lasted
      for 6 weeks to 6 months; the itching was very resistant to therapy (f.e. with
      antihistaminics). We want to draw the attention to this possible, in the
      literature until now quite neglected, for some patients extremely uncomfortable
      and socially embarrassing side effects after HES-therapy when given in relatively
      high doses. It is therefore suggested therapeutic recommendations should be
      developed to prevent this undesired side effect.

PMID- 1372782
TI  - [The fresh weight and the concentration of DNA, RNA and protein in different
      tissues of swine of different ages].
AB  - Female pigs aged between one day (body weight 1.39 +/- 0.20 kg) and 1123 days (b.
      w. 233 +/- 32 kg) were allotted to 10 groups of various age and analyses of the
      concentration of DNA, RNA and protein in 9 different tissues were performed. The
      wet weight: DNA-, the protein: DNA- and the RNA: DNA-ratio were determined. With
      the exception of the liver the content in DNA, RNA and protein increased to the
      age of 1123 days. The highest fresh weight: DNA ratio of 2041 was reached on the
      1123rd day in the M.longissimus; the smallest (111) existed at this time in the
      spleen. In the liver the highest content in fresh weight, in DNA and RNA was
      found on the 180th day. The smallest increases in the content of DNA and RNA in
      the mentioned period were in the brain, the highest in the spleen, the liver and
      the M.longissimus dorsi. The values can be used as a basis for studies on the
      influence of feeding and of diseases (infections) on growth.

PMID- 1372783
TI  - [Demonstration of glycosaminoglycans (GAGs) in fetal human trabecular tissue].
AB  - The ultrastructural localization of glycosaminoglycans (GAGs) in the developing
      human outflow apparatus was investigated. The aqueous outflow system from human
      eyes at 26th and 36th fetal week and 2 years of age was stained with ruthenium
      red to identify GAGs with the transmission electron microscope. Luminal surface
      of the inner wall of the Schlemm's canal, basal lamina of the endothelial cells,
      basal lamina-like material, amorphous substances and collagen fibrils in juxta
      canalicular tissue were associated with ruthenium red-stainable material. The
      basal lamina of the endothelial cells of Schlemm's canal was stained less
      obviously in 2-year-old trabecular tissue. The composition of the ruthenium red
      stainable material was determined by treatment of each tissue with streptomyces
      hyaluronidase, chondroitinase AC, and chondroitinase ABC respectively. Hyaluronic
      acid was identified in each ruthenium red-stainable extracellular component.
      Chondroitin sulfate was identified in all ruthenium red-stainable components
      except luminal surface of the canal. The presence of dermatan sulfate was
      confirmed in the amorphous components and collagen fibrils of juxta-canalicular
      tissue. The results suggest that GAGs in fetal trabecular tissue already
      contribute to the outflow resistance and that alterations of the pattern of GAGs
      may take place as development proceeds.

PMID- 1372784
TI  - [Lymphocyte subsets of peripheral blood in patients with sarcoidosis].
AB  - Cytofluorometric analysis of lymphocyte subsets was performed in the peripheral
      blood samples from fifteen sarcoidosis patients with uveitis as well as normal
      controls. The percentage of T cells (CD3+) was significantly decreased, whereas
      that of B cells (CD19+) was markedly increased in patients with sarcoidosis
      compared to controls. Natural killer cells (CD8+CD57+) as well as activated T
      cells (CD3+HLA-DR+) were significantly increased in patients with sarcoidosis.
      The percentage of the Leu 1-B cells and the ratio of Leu 1-B/B were significantly
      higher in sarcoidosis patients with respect to controls. Moreover, the ratio of
      Leu 1-B/B was significantly correlated with the serum level of angiotensin
      converting enzyme (ACE) in sarcoidosis. Therefore, it is considered that the Leu
      1-B/B value could be a useful indicator not only for the activity but also for
      the diagnosis of sarcoidosis. No significant difference was found in any subset
      between the patients with active uveitis and patients with inactive uveitis.

PMID- 1372785
TI  - Pharmacology of bepridil.
AB  - Bepridil is an antianginal agent with multiple therapeutic actions. It decreases
      calcium influx through potential-dependent and receptor-operated sarcolemmic
      calcium channels and acts intracellularly as a calmodulin antagonist and calcium
      sensitizer. Thus, in cardiac muscle it enhances the sensitivity of troponin C to
      calcium, stimulates myofibrillar adenosine triphosphatase activity, removes
      calmodulin's inhibitory effect on sarcoplasmic reticulum calcium release, and
      inhibits sodium-calcium exchange--actions that tend to offset the effects of
      calcium influx blockade on cardiac contractile force. However, in vascular smooth
      muscle where the calcium-calmodulin complex promotes muscle contraction by
      activating myosin light-chain kinase phosphorylation of contractile proteins,
      calmodulin antagonism, coupled with bepridil's blockade of calcium influx, leads
      to vasorelaxation. In animal models of ischemia, bepridil and other calmodulin
      inhibitors show antiarrhythmic efficacy following reperfusion. Additionally,
      interfering with calmodulin's role in sympathetic nerve terminal function may
      help to limit the ischemia-induced catecholamine release that contributes to
      arrhythmogenesis. Bepridil shows a lidocaine-like fast kinetic block of inward
      sodium current (as distinct from the slow or intermediate kinetic inhibition
      expressed by encainide or quinidine, respectively). This inhibition is pH
      dependent; activity is expressed to a greater degree at lower pH levels. This,
      this potentially antiarrhythmic mechanism is activated by conditions of ischemia.
      Bepridil's blockade of outward potassium currents and its inhibition of sodium
      calcium exchange increase action potential duration and ventricular
      refractoriness, prolong the QT interval, and form the basis for a class III
      antiarrhythmic mechanism. Because hypokalemia also prolongs the QT interval, the
      addition of bepridil in the presence of hypokalemia can lead to excessive
      prolongation. Bepridil both increases myocardial oxygen supply through coronary
      vasodilation and decreases myocardial oxygen demand through mild heart rate and
      afterload reduction, and shows potential antiarrhythmic activity through class
      IB, III, and IV mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372786
TI  - Digital rectal examination-associated alterations in serum prostate-specific
      antigen.

PMID- 1372787
TI  - Evidence for the transformation of seminoma to yolk sac tumor, with histogenetic
      considerations.
AB  - Recent ultrastructural, cytogenetic, and ploidy analyses indicate that seminoma
      acts as a precursor from which other forms of testicular germ cell tumor may
      originate. Ten cases of primary or metastatic testicular germ cell tumors were
      investigated that showed possible transformation of seminoma to yolk sac tumor.
      Such transformation was identified in six cases in which foci of abrupt change
      from seminoma to various patterns of yolk sac tumor occurred, often at the
      periphery of otherwise pure lobules of seminoma. Immunostains for cytokeratins,
      placental-like alkaline phosphatase, and alpha-fetoprotein demonstrated the
      expected changes in reactivity at the foci of such transformation. Four
      additional cases were regarded as either seminomas with artifactual microcystic
      change or the close association of seminoma and yolk sac tumor but lacking
      evidence for transformation. These data support the theory that seminoma is not
      an "endpoint" neoplasm but may serve a precursor role in the progression to
      nonseminomatous germ cell tumors.

PMID- 1372788
TI  - Digital rectal examination-associated alterations in serum prostate-specific
      antigen.
AB  - The effect of digital rectal examination (DRE) on measurement of serum prostate
      specific antigen was investigated during a prostate cancer screening program of
      2,736 ambulatory men. Serum samples were collected before and after DRE and
      values compared using the nonparametric Wilcoxon signed rank test. Small, yet
      statistically significant, increases were found associated with DRE. The
      magnitude of these increases, however, was of minor clinical importance. Patients
      who exhibited the largest increases with initial values greater than the upper
      limit of normal (4 micrograms/L) were found to have either benign prostatic
      hyperplasia, prostatitis, or prostatic carcinoma. The benign prostatic
      hyperplasia patients showed relatively low initial prostate-specific antigen
      values with similarly small increases related to DRE, whereas the prostatitis and
      cancer patients exhibited both higher initial prostate-specific antigen values
      and larger increases associated with DRE. Finally, patients with increases in
      prostate-specific antigen from less than 4 micrograms/L to greater than or equal
      to 4 micrograms/L comprised less than 2% of the reference range population, the
      majority of whom had post-DRE measurements of less than 5 micrograms/L. Thus, DRE
      does not appear to be a significant factor in falsely elevating prostate-specific
      antigen levels and should be of limited concern to the clinician obtaining serum
      samples after DRE.

PMID- 1372789
TI  - Current issues in maternal serum alpha-fetoprotein screening.
AB  - Measurement of maternal serum alpha-fetoprotein originated in the early 1970s as
      a means to screen for fetal neural tube defects, a relatively common and
      devastating class of malformations. Since that time, assay methods have improved,
      interpretation has been refined, follow-up testing for neural tube defects has
      advanced, and many other disease associations have been uncovered. It is a unique
      test, both in its clinical application and its laboratory implementation. The
      present review outlines current procedures for maternal serum alpha-fetoprotein
      screening and summarizes recent developments.

PMID- 1372790
TI  - Eosinophilia associated with chronic pancreatitis: an analysis of 122 patients
      with definite chronic pancreatitis.
AB  - Among 122 patients with chronic pancreatitis, marked eosinophilia (greater than
      500 eosinophils/mm3 in the peripheral blood) was observed in 21 cases (17.2%).
      All of the affected patients were males, and there was no significant difference
      in the incidence of eosinophilia between patients with alcoholic and nonalcoholic
      pancreatitis. In the patients with eosinophilia, endocrine pancreatic function
      was maintained comparatively well, despite marked exocrine pancreatic
      dysfunction. The eosinophilia of chronic pancreatitis frequently developed in
      association with severe damage to neighboring organs (pleural effusion,
      pericarditis, and ascites), as well as in association with pancreatic pseudocyst.
      Our findings suggest that there is a close correlation between marked
      eosinophilia and severe tissue injury during acute exacerbations of chronic
      pancreatitis.

PMID- 1372791
TI  - Effect of a high dose of ethanol on serum pancreatic enzymes in young healthy
      adults.
AB  - Short-term effects of a high dose of ethanol on the serum activities of
      pancreatic enzymes were studied in young healthy adults. There were 10 males and
      10 females in the study group, and two males and three females in the control
      group. In the study group, ethanol (2 g/kg of body weight) was given during 4 h,
      resulting in the blood ethanol level of 1.6 +/- 0.3 g/l at 6 h. No significant
      changes in serum pancreatic enzyme activities were observed in the control group
      during the 56-h experiment. In the study group, none of the individuals
      demonstrated a marked increase (double from the baseline) in serum pancreatic
      enzyme activities. In the male study group, the serum total amylase activity
      increased slightly at 6 h, but the serum pancreatic isoamylase activity remained
      unchanged. These data suggest that, in nonalcoholic individuals, short-term
      exposure to a high dose of ethanol does not induce such injury in the pancreas
      that would appear as a leak of enzymes from the acinar cells into the
      circulation.

PMID- 1372792
TI  - Granulomatous gastritis and Whipple's disease.
AB  - Granulomatous gastritis is an uncommon morphological diagnosis. An
      etiopathogenetic diagnosis can be reached only by combining the morphological
      examination with clinical and laboratory investigations. The diagnosis of
      Whipple's disease in our patient was based upon a classical clinical picture and
      upon the likewise classical morphological appearance of the small intestinal
      mucosal biopsy. To our knowledge, this case report is the first to describe
      granulomatous gastritis in a patient with Whipple's disease.

PMID- 1372793
TI  - Maternal serum alpha-fetoprotein screening and fetal chromosome anomalies: is
      lowering maternal age for amniocentesis preferable?
AB  - We have compared the cytogenetic abnormalities diagnosed prenatally in 1,098
      patients referred for amniocentesis because of low maternal serum alpha
      fetoprotein (MSAFP) to those of 445 patients whose indication was elevated MSAFP
      and those of 361 patients who had amniocentesis for "maternal anxiety." Autosomal
      trisomies, sex chromosome aberrations, and various structural rearrangements were
      detected in all 3 groups and actually exceeded the age-related incidence
      estimates. The frequency of chromosome anomalies in cases studied because of
      "maternal anxiety" with no prior screening was similar to that in the group
      referred for low MSAFP (1.38 and 1.27%, respectively). A relatively higher
      frequency (2.02%) was detected in the group whose indication was elevated MSAFP.
      Maternal serum screening is designed primarily to recalculate risk figures for
      Down syndrome, but not for other major chromosome abnormalities. The concept of
      prenatal screening for chromosome aberrations must therefore be reevaluated. We
      think that efforts should be directed at making amniocenteses more accessible to
      patients who request it. "Lowering" maternal age limits to 30 would encompass a
      greater proportion of pregnancies at risk and would be a step toward more
      effective prenatal diagnosis for chromosome abnormalities.

PMID- 1372794
TI  - Depression and Parkinson's disease: a review.
AB  - OBJECTIVE: The purpose of this review is to provide an update of the research
      regarding depression in Parkinson's disease and to synthesize the information
      into a neurobiological model relating the structural and biochemical changes in
      this disorder to the behavioral manifestations. METHOD: The author used a
      computer-based search of the literature, augmented by extensive bibliography
      guided article reviews, to find information on depression and Parkinson's
      disease. FINDINGS: Depression occurs in approximately 40% of patients with
      Parkinson's disease; depression in Parkinson's disease is distinguished from
      other depressive disorders by greater anxiety and less self-punitive ideation.
      Lower CSF levels of 5-hydroxyindoleacetic acid, a past history of depression, and
      greater functional disability are associated with a greater risk of depression in
      Parkinson's disease. Female gender, early age at onset of Parkinson's disease,
      and greater left brain involvement may also be risk factors. Approximately half
      of depressed patients with Parkinson's disease meet criteria for major depressive
      episodes; half have dysthymia. Depression is more common in Parkinson's disease
      with prominent bradykinesia and gait instability than in tremor-dominant
      syndromes. Depressed patients with Parkinson's disease have greater frontal lobe
      dysfunction and greater involvement of dopaminergic and noradrenergic systems
      than nondepressed patients with the disease. Mood changes in Parkinson's disease
      respond to treatment with conventional tricyclic antidepressants or ECT.
      CONCLUSIONS: Neurobiological investigations suggest that depression in
      Parkinson's disease may be mediated by dysfunction in mesocortical/prefrontal
      reward, motivational, and stress-response systems. Neuropsychological, metabolic,
      clinical, pharmacological, and anatomical studies support the involvement of
      frontal dopaminergic projections in patients with Parkinson's disease and
      depression.

PMID- 1372795
TI  - Macrophage development: I. Rationale for using Griffonia simplicifolia isolectin
      B4 as a marker for the line.
AB  - The isolectin B4 of Griffonia simplicifolia (GSA I-B4) binds to cell membrane
      glycoconjugates bearing terminal alpha-D-galactose, which macrophages possess. We
      have investigated the merits of its use as a marker for cells of this lineage
      when examining the early origin of macrophage populations in rat embryos, the
      stages and time scale of transformation from precursor forms to active, matured
      cells, and the response of precursors and macrophages to colony-stimulating blood
      factors, the last two studies conducted in organ cultures of prenatal lungs. In
      the present instance, GSA I-B4 was used either coupled with fluorescein (FITC)
      for light microscopy of living and fixed cells, or with peroxidase for light or
      electron microscopy. Control incubations of lung culture-derived macrophages
      proved that staining resulted from specific binding to galactosyl units on the
      cell membrane, since it was competitively inhibited by alpha-D-galactose. The
      lectin binds to few cells in 14-day prenatal lung explants but to a great many
      macrophages that subsequently develop in the cultures, indicating that it can be
      relied on for quantitative studies on population growth; however, it is important
      to provide reagents with good access to the cells. Apart from macrophages and
      their precursors, virtually no cells in prenatal lung cultures bind this lectin.
      Granulocytes of adult blood are GSA positive, but they are not yet present in 14
      day prenatal explants and do not develop subsequent to culturing; hence they are
      not a source of confusion for experimental studies using this system. Precursors
      of granulocytes begin to appear in rat embryos around day 13 and have GSA
      positive cell membranes, but like definitive granulocytes they also have
      conspicuous peroxidase-positive lysosomal granules which serve to distinguish
      them from early macrophages, particularly when cells are studied at an
      ultrastructural level. With these objections cleared away, GSA I-B4 emerges as a
      valuable means to mark cells of the macrophage line, mature or immature.

PMID- 1372796
TI  - Effects of neuraminidase on airway reactivity in the guinea pig.
AB  - We investigated the effects of neuraminidase, a viral enzyme that cleaves alpha
      ketosidic cell-bound sialic acids, to see if it accounts for parainfluenza and
      influenza virus-induced airway hyperreactivity. Accordingly, Vibrio cholerae
      neuraminidase was administered intratracheally in guinea pigs, and airway
      reactivity was assessed 3 h later. Removal of sialic acid residues was evaluated
      by histologic studies. Airway responsiveness was determined in anesthetized,
      tracheotomized, and mechanically ventilated guinea pigs by exposing them to
      increasing concentrations of aerosolized bronchoconstrictor agents. Respiratory
      system conductance was measured by the occlusion method. Neuraminidase injected
      intratracheally did not change airway reactivity to 10(-4) to 10(-2) M
      acetylcholine or 10(-4) to 2.5 x 10(-3) M histamine; nor did it prevent
      aerosolized albuterol from inhibiting histamine-induced bronchoconstriction.
      Substance P (10(-6) to 5 x 10(-5) M) had no significant bronchoconstrictor effect
      on guinea pigs pretreated with saline or neuraminidase. In guinea pigs pretreated
      with aerosols of the neutral endopeptidase inhibitor phosphoramidon (10(-4) M)
      before the concentration curve to aerosolized substance P was recorded,
      neuraminidase significantly reduced substance P-induced bronchoconstriction. When
      bronchoconstriction was induced by the 4-11 fragment of substance P (10(-5) to
      10(-2) M), which is devoid of positive charges, it did not differ significantly
      in guinea pigs pretreated with saline and those pretreated with neuraminidase.
      These results indicate that in the guinea pig, neuraminidase injected
      intratracheally does not induce non-specific airway hyperreactivity and may alter
      the binding of substance P to its receptors.

PMID- 1372797
TI  - Protein kinase C: a target for anti-inflammatory therapy?

PMID- 1372798
TI  - Disposition of beta-hexachlorocyclohexane, p,p'-DDT, and trans-chlordane
      administered subcutaneously to monkeys (Macaca fascicularis).
AB  - To evaluate skin lipid analysis for the accumulation level of environmental
      pollutants, the correlations between organochlorine pesticide residues in adipose
      tissue, blood, and skin lipids of monkeys were studied. The mixture of beta
      hexachlorocyclohexane (beta-HCH), p,p'-DDT, and trans-chlordane was
      subcutaneously given to monkeys once weekly for 5 weeks at dose levels of 1 and
      10 mg/kg. The chemicals distributed in adipose tissue, blood, and skin lipids
      were determined six times after the last dosing at intervals of 4 to 9 weeks.
      Oxychlordane and p,p'-DDE were detected in all tissues together with the
      administered chemicals. In blood and adipose tissue, trans-chlordane decreased
      rapidly and oxychlordane and p,p'-DDE increased gradually and then remained at
      constant levels. beta-HCH and p,p'-DDT in adipose tissue increased until the 12th
      week and then decreased in all animals. The correlation coefficients between
      blood and adipose tissue regardless of dose level and collection time for each
      chemical ranged from 0.83 to 0.94. Correlation coefficients between skin lipids
      and adipose tissue varied with the chemical, namely, 0.31, 0.72, 0.81, 0.81, and
      0.83 for p,p'-DDE, trans-chlordane, p,p'-DDT, beta-HCH, and oxychlordane,
      respectively. The results indicated that skin lipid analysis may be useful for
      the evaluation of specific pollutants in the body burden.

PMID- 1372799
TI  - Effect of deoxynivalenol on neurotransmitters in discrete regions of swine brain.
AB  - The effect of deoxynivalenol (DON, vomitoxin) on brain amine levels was
      investigated in swine. DON, a trichothecene mycotoxin, causes suppression of feed
      intake (anorexia) in susceptible species. Following acute administration of DON
      to pigs (0.25 mg/kg, IV), concentrations of endogenous catecholamines
      norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenyl-acetic acid (DOPAC), and
      homovanillic acid (HVA), and the indoleamines, 5-hydroxytryptamine (5HT,
      serotonin) and 5-hydroxyindoleacetic acid (5HIAA) were determined in five brain
      regions, periodically during the 24 h post-dosing. Analysis was carried out by
      high performance liquid chromatography, using electrochemical detection. Effects
      of DON in the swine brain were transmitter, time and region-specific. It was
      observed that levels of the major transmitters (NE, DA and 5HT) were
      statistically different from controls in the hypothalamus (Hypo), frontal cortex
      (FCX) and cerebellum (Cb) up to 8 h post-dosing. Overall, DON administration
      elevated NE and depressed DA concentrations in these regions, and levels of 5HT
      which increased initially in Hypo (1 h), had dropped significantly below controls
      in both Hypo and FCX at 8 h. These alterations, however, were not indicative of
      known neurochemical changes associated with chemical-induced anorexia. Instead,
      this data suggested that the neurochemical effects of acute DON exposure might be
      due to peripheral toxicological events (i.e., vomiting), which overwhelmed its
      more subtle feed refusal activity.

PMID- 1372800
TI  - The rate of decline of alpha- and beta-benzene hexachloride residues in
      contaminated pigs.

PMID- 1372801
TI  - Proteoglycan synthesis in human erythroleukaemia (HEL) cells.
AB  - Synthesis of sulphated proteoglycans was compared in human erythroleukaemia (HEL)
      cells grown under control conditions and under stimulation by dimethyl sulphoxide
      (DMSO) and phorbol 12-myristate 13-acetate (PMA). Synthesis of [35S]sulphate
      labelled proteoglycans by DMSO-treated cells was decreased by about 35% relative
      to controls, but synthesis of proteoglycans by PMA-treated cells increased 3-4
      fold. Control and DMSO-treated cells secreted 65% of the newly synthesized
      proteoglycans, but PMA-treated cells secreted more than 90%. Sepharose CL-6B
      chromatography and SDS/PAGE suggested the presence of several proteoglycans in
      the cells and culture medium. The PMA-treated cells synthesized a low-Mr
      proteoglycan (Kav. 0.3( that was not present in controls and DMSO-treated
      cultures. The proteoglycans of the cells and medium from control, DMSO-treated
      and PMA-treated cultures could be separated into three fractions by octyl
      Sepharose chromatography. The proteoglycans were resistant to trypsin but were
      degraded by Pronase and papain to fragments similar in size to the NaOH/NaBH4
      generated glycosaminoglycans. The average chain length of the glycosaminoglycans
      (Kav. 0.20 on Sepharose CL-6B for controls) was decreased by DMSO (Kav. 0.25) and
      by PMA (Kav. 0.30-0.38). Chondroitin ABC lyase digestion of the proteoglycans
      from the medium of the control cultures produced two core proteins at Mr 31,000
      and 36,000. The DMSO medium proteoglycans had only the 31,000-Mr core protein,
      and the PMA culture medium proteoglycans had core proteins of Mr 27,000, 31,000
      and 36,000. Changes in synthesis of proteoglycans induced by DMSO or PMA may have
      relevance for the maturation of haematopoietic cells.

PMID- 1372802
TI  - Conformational differences between surface-bound and fluid-phase complement
      component-C3 fragments. Epitope mapping by cDNA expression.
AB  - In previous studies a subset of complement-component-C3 (C3) epitopes, C3(D),
      expressed in denatured and surface-bound C3 and C3 fragments, has been described.
      These epitopes were detected by antibodies raised against denatured C3. In the
      present study we used a cDNA expression strategy to localize epitopes recognized
      by monoclonal and polyclonal anti-C3(D) antibodies. First, DNAse I digestion of
      C3 cDNA was used to generate 200-300 bp fragments. These cDNA fragments were
      expressed as beta-galactosidase-C3 fusion proteins using the lambda gt11 vector.
      The fusion proteins were tested by Western-blot analysis for reactivity with
      monoclonal and polyclonal anti-C3 antibodies, and the location of the epitopes
      were determined by sequencing the cDNA fragments. Affinity-purified polyclonal
      anti-C3(D) antibodies specific for denatured C3 reacted strongly with the C3
      fusion fragments corresponding to segments of the 40 kDa subunit of C3c (residues
      1477-1510) and the C3d fragment (residues 1117-1155 and 1234-1294) of C3.
      Adsorption of the polyclonal antibodies with a mixture of EAC3b and EAC3bi
      (degradation fragments of C3 bound to sheep erythrocytes) abolished binding to
      fusion proteins spanning the C3d region, but not the 40 kDa fragment of C3c. No
      effect was seen with the corresponding soluble C3 fragments. The monoclonal anti
      C3(D) antibodies (mAbs) 7D326.1 and 7D331.1, specific for EAC3b and EAC3bi, bound
      to a fusion protein corresponding to amino acid residues 1312-1404, whereas mAb
      7D9.2, specific for EAC3d, reacted with a fusion protein spanning amino acid
      residues 1082-1118. mAbs 4SD11.1 and 4SD18.1, which did not bind to any
      physiological C3 fragment, detected a fusion protein covering residues 1477-1510.
      In summary, the segments of C3 represented by amino acid residues 1082-1118, 1117
      1155, 1234-1294 and 1312-1404 accommodate C3(D) epitopes that are expressed by
      erythrocyte-bound C3 fragments, but not by the corresponding fluid-phase
      fragment, whereas the segments spanning residues 973-1026 and 1477-1510 contain
      C3(D) epitopes that are exposed exclusively in denatured C3 and therefore hidden
      in physiological fragments of the protein.

PMID- 1372803
TI  - Phosphorylation of elongation factor 2 during Ca(2+)-mediated secretion from rat
      parotid acini.
AB  - In this paper we report the rapid phosphorylation of a cytosolic 100 kDa protein
      during stimulation of secretion from dispersed aggregates of parotid acinar cells
      with Ca(2+)-mobilizing secretagogues (carbachol, Substance P, ATP and the Ca2+
      ionophore A23187). Phosphorylation was inhibited by removal of extracellular Ca2+
      but was not observed during stimulation with phorbol esters, suggesting that this
      protein is not a substrate for protein kinase C. Two-dimensional PAGE and
      immunoprecipitation with a specific antiserum indicated that this protein is
      elongation factor 2, whose Ca2+ calmodulin-dependent phosphorylation has been
      shown to inhibit protein synthesis [Nairn & Palfrey (1987) J. Biol. Chem. 262,
      17299-17303]. These results suggest that phosphorylation of elongation factor 2
      is the molecular mechanism for the inhibition of protein synthesis which has been
      previously observed in rat parotid cells during stimulation with Ca(2+)
      mobilizing secretagogues.

PMID- 1372804
TI  - Interaction between the calcium and cyclic AMP messenger systems in perifused rat
      parotid acinar cells. Possible mechanism for potentiation of amylase secretion.
AB  - Potentiation of amylase secretion induced by a combination of isoproterenol and
      carbamylcholine was examined in perifused rat parotid acinar cells. The time
      course of changes in the augmented amylase secretion induced by isoproterenol
      plus carbamylcholine was similar to that induced by carbamylcholine alone, but
      not to that caused by isoproterenol. Concentration-response analysis showed that
      isoproterenol increased the apparent affinity for carbamylcholine to stimulate
      amylase secretion with the maximum effect attained by isoproterenol plus
      carbamylcholine being higher than that attained by isoproterenol or
      carbamylcholine. 8-Bromo cyclic AMP, forskolin and 3-isobutyl-1-methylxanthine
      mimicked the effect of isoproterenol. Calcium ionophores (A23187 and ionomycin),
      but not phorbol 12,13-dibutyrate, mimicked the effect of carbamylcholine.
      Chelation of intracellular free calcium with 1,2-bis-[2-aminophenoxyl]-ethane
      N,N,N',N'-tetraacetic acid, but not that of extracellular calcium with
      [ethylenebis(oxyethylenenitrile)]-tetraacetic acid (EGTA), abolished the
      potentiation. Calmodulin antagonists inhibited amylase secretion induced by
      isoproterenol plus carbamylcholine or carbamylcholine alone, but not that induced
      by isoproterenol alone. These results suggest that the potentiation is mainly, if
      not completely, caused by a coordinated interaction between the cyclic AMP system
      and the Ca2+ system at a step distal to second messenger generation, probably via
      a cyclic AMP-induced increase in the sensitivity of the Ca2+ response element to
      calcium.

PMID- 1372805
TI  - A pleiotropic response to phenobarbital-type enzyme inducers in the F344/NCr rat.
      Effects of chemicals of varied structure.
AB  - The effects of a number of phenobarbital-type inducers on selected drug
      metabolizing enzymes in male F344/NCr rats were determined by measuring specific
      catalytic activities and/or by measuring the levels of RNA which hybridize with
      specific probes for the corresponding genes. The effects on hepatic CYP2B1 were
      assessed by measuring the levels of CYP2B1-specific RNA and benzyloxyresorufin O
      dealkylase and testosterone 16 beta-hydroxylase activities. Levels of CYP3A were
      monitored by measuring the rate of hydroxylation of testosterone at the 6 beta
      position. Microsomal epoxide hydrolase activity was determined by measurement of
      cellular RNA specific for this form and by assaying the hydrolysis of
      benzo[a]pyrene-4,5-oxide. UDP-glucuronyltransferase activity was assayed by
      measuring the glucuronidation of 3-hydroxybenz[a]anthracene. Levels of
      glutathione S-transferase Ya/Yc were measured by quantifying total cellular RNA
      coding for the proteins. When male F344/NCr rats were administered various doses
      of phenobarbital or dichlorodiphenyltrichloroethane (DDT), strong correlations
      between the induction of CYP2B1 and the induction of epoxide hydrolase or UDP
      glucuronyltransferase activities were observed. Treatment of rats with
      barbiturates, hydantoins, halogenated pesticides such as DDT or alpha
      hexachlorocyclohexane, 2,4,5,2',4',5'-hexachlorobiphenyl, CYP2B1 inhibitors such
      as clotrimazole or clonazepam, or such structurally-diverse compounds as 2
      hexanone or diallyl sulfide resulted in induction of CYP2B1-mediated enzyme
      activity and induction of certain other forms of cytochrome P450, microsomal
      epoxide hydrolase, at least one form of UDP-glucuronyltransferase, and multiple
      forms of glutathione S-transferase. This suggests that, as a class, compounds
      which induce CYP2B1 also induce a coordinate hepatic pleiotropic response which
      includes induction of these other phase I and phase II drug-metabolizing enzymes.

PMID- 1372806
TI  - Effects of anti-allergic drugs on human neutrophil superoxide-generating NADPH
      oxidase.
AB  - The effects of anti-allergic drugs with or without H1-receptor antagonism on the
      NADPH oxidase (EC 1.6.99.6) from human neutrophils in both whole-cell and fully
      soluble (cell-free) systems were investigated. Three anti-allergic drugs with H1
      receptor antagonism, azelastine, ketotifen and oxatomide, were found to inhibit
      the superoxide generation of human neutrophils exposed to phorbol myristate
      acetate in a whole-cell system and the activation of superoxide-generating NADPH
      oxidase by sodium dodecyl sulfate in a cell-free system. The concentrations of
      these drugs required for 50% inhibition of the oxidase (IC50) were: azelastine-
      0.7 microM in the whole-cell system and 0.5 microM in the cell-free system;
      ketotifen--60 microM in the whole-cell system and 6.8 microM in the cell-free
      system; and oxatomide--25 microM in the whole-cell system and 9.7 microM in the
      cell-free system. In addition, in the cell-free system, these drugs did not
      change the Km values for the NADPH of the oxidase. However, these drugs did not
      inhibit the superoxide generation of NADPH oxidase after its activation in whole
      cell and cell-free systems, suggesting that these drugs do not have superoxide
      scavenger actions. Concentrations of less than 200 microM of anti-allergic drugs
      without H1-receptor antagonism, tranilast, repirinast and ibudilast, did not
      inhibit neutrophil NADPH oxidase in whole-cell and cell-free systems. The IC50 of
      hydrocortisone in the cell-free system was 60 microM. These results suggest that
      anti-allergic drugs with H1-receptor antagonism inhibit activation of the
      solubilized membrane-bound enzyme by sodium dodecyl sulfate in cell-free systems
      and that they have much stronger anti-inflammatory action than hydrocortisone.

PMID- 1372807
TI  - Modulation of melphalan uptake in murine L5178Y lymphoblasts in vitro by changes
      in ionic environment.
AB  - The alkylating agent melphalan is actively transported in mammalian cells by two
      amino acid transport carriers: the sodium-dependent carrier with substrate
      preference for alanine-serine-cysteine (system ASC), and a sodium-independent
      carrier with preference for leucine (system L). The effect of altering the ionic
      environment of murine L5178Y lymphoblasts was investigated in order to determine
      not only the direct effects of hydrogen and calcium ions on these transport
      systems, but also the indirect effects of agents or modulators known to alter
      intracellular calcium. Melphalan transport followed a bell-shaped distribution
      curve over a pH range from 3 to 9 with a pH optimum of 4.3 and 4.6 for transport
      by systems ASC and L, respectively. Those agents that could cause a decrease in
      cytosolic calcium such as the calcium channel blockers verapamil, diltiazem and
      nitrendipine, the calcium chelator (ethyleneglycol-bis-(beta-aminoethylether)
      N,N,N',N'-tetraacetic acid (EGTA) and reduction of pH were found to augment
      melphalan uptake, whereas conditions that would elevate intracellular calcium
      such as the calcium ionophore A23187, the calcium channel agonist (-) Bay K 8644,
      elevation of extracellular calcium and the calcium pump inhibitor trifluoperazine
      were all found to decrease melphalan uptake. These findings suggest that
      modification of ionic environment directly or indirectly by agents known to alter
      intracellular calcium can modulate melphalan uptake.

PMID- 1372808
TI  - Highly acetylated H4 is associated with histone displacement in rat spermatids.
AB  - The presence of highly acetylated histone H4 during spermatogenesis was studied
      to evaluate its correlation with the events of gene transcription, histone
      deposition, and histone displacement. We utilized an antibody raised to a
      pentaacetylated synthetic peptide that preferentially recognizes highly (tetra-
      and tri-) acetylated forms of rat testis H4. Electrophoretic separation of
      histones from enriched fractions of spermatogenic cells followed by detection of
      these forms by staining and by immunoblotting using this antibody showed that the
      highly acetylated forms were limited almost exclusively to spermatids beginning
      at step 11 of development. Immunoflurescence also revealed a striking polarity in
      the progression of histone from the spermatid nucleus. Highly acetylated H4 was
      displaced from the anterior to the caudal portion of the spermatid nucleus during
      steps 11 and 12, along with other histones, prior to their displacement by
      transition proteins. Thus, while monoacetylated and low levels of diacetylated
      forms of H4 were associated with stages at which histone deposition and
      transcription occur, the more highly acetylated forms appeared in high levels
      only at the stage at which histone displacement occurs.

PMID- 1372809
TI  - Effect of fetal haemoglobin on the accuracy of pulse oximetry in preterm infants.
AB  - Pulse oximeters are programmed with a calibration curve derived from studies done
      in adults. Whether fetal haemoglobin levels affect their reliability is unclear.
      This study reports the accuracy of pulse oximetry in 22 preterm infants (mean 31
      weeks, range 25-36 weeks gestation) between 1 h and 73 days of age. Oxygen
      saturation obtained from a Nellcor N-200 pulse oximeter (SpO2) was compared with
      simultaneous arterial values (functional SaO2) measured by a Radiometer OSM3
      Hemoximeter over a SpO2 range of 83-99%. Fetal haemoglobin (HbF),
      carboxyhaemoglobin (HbCO) and methaemoglobin (HbMet) measured by the hemoximeter
      ranged between 0-100%, 0-3.5% and 0-0.8% respectively. Linear regression analysis
      revealed a close correlation between SpO2 and functional SaO2 (SpO2 = 0.75 SaO2 +
      24.43, r = 0.88, P less than 0.001) over a wide range of values for PCV, heart
      rate, blood pressure, PaO2, PaCO2 and pH. The mean SpO2-SaO2 difference of 1.3,
      (s.d. 2.5%, P less than 0.001) was unaffected by HgF, HbCO or HbMet but was
      increased in infants receiving inotropic support. We conclude that the Nellcor N
      200 pulse oximeter gives reliable oxygen saturation measurements unaffected by
      the HbF level in preterm infants.

PMID- 1372810
TI  - The role of insulin-sensitive phosphodiesterase in insulin action.
AB  - The physiological role of the insulin-sensitive phosphodiesterase in mediating
      the antilipolytic actions of insulin was investigated in rat fat cells with two
      phosphodiesterase inhibitors, namely, 3-isobutyl-1-methylxanthine (IBMX) and
      griseolic acid. Insulin activates the phosphodiesterase when incubated with
      intact fat cells and blocks isoproterenol-induced cellular cAMP production and
      lipolysis, in a time- and dose-dependent manner. High concentrations of IBMX (1
      mM), but not lower concentrations (0.1 mM), increased fat cell cAMP levels and
      lipolytic responses and overcame the antilipolytic effects of insulin; however,
      this treatment does not inhibit insulin-stimulated phosphodiesterase activity at
      earlier times (less than 30 min of incubation). These results may suggest that
      the level of cAMP under these conditions may be sufficient to stimulate lipolysis
      maximally, even though increases in cellular cAMP accumulation associated with
      the higher concentration of IBMX (1 mM) are partially suppressed by insulin.
      Cellular cAMP accumulation and the phosphodiesterase activation induced by IBMX
      are suppressed by the nonhydrolyzable adenosine analogue N6
      phenylisopropyladenosine (PIA). These results suggest the involvement of
      adenosine receptors in mediating these responses. A novel phosphodiesterase
      inhibitor, griseolic acid, suppresses basal phosphodiesterase activity
      (approximately 50%), increases cellular cAMP content, and stimulates lipolysis in
      intact fat cells. It also partially suppresses insulin-stimulated
      phosphodiesterase activity (approximately 50%) and reduces the ability of insulin
      to decrease cellular cAMP concentration (approximately 40%) and lipolysis
      (approximately 65%). Because, unlike IBMX and other drugs, griseolic acid
      demonstrates only inhibition of phosphodiesterase activity, it may be a useful
      tool for studying the mechanism of insulin action in intact cells. The present
      work supports the concept that insulin's antilipolytic action is mediated by an
      activation of fat cell phosphodiesterase.

PMID- 1372811
TI  - Phosphodiesterases in vascular endothelial cells.

PMID- 1372812
TI  - Pharmacological manipulation of tissue cyclic AMP by inhibitors. Effects of
      phosphodiesterase inhibitors on the functions of platelets and vascular
      endothelial cells.

PMID- 1372813
TI  - Therapeutic potential of isozyme-selective phosphodiesterase inhibitors in the
      treatment of asthma.

PMID- 1372814
TI  - Cyclic-AMP-dependent positive chrono- and inotropic responses in the blood
      perfused dog atrium.

PMID- 1372815
TI  - Stenting of the arterial duct: a new approach to palliation for pulmonary
      atresia.
AB  - OBJECTIVE: To assess the possibility of maintaining ductal patency in neonates
      with complex pulmonary atresia by percutaneous implantation of balloon expandable
      stents. PATIENTS: Two duct-dependent neonates with long segment pulmonary
      atresia, right sided aortic arch, and left sided arterial duct. RESULTS: Stents
      with final diameter of 3.5 or 4 mm and initial length of 7 or 15 mm were
      successfully positioned in the arterial duct. Two stents were required in one
      child and four in the other in order to stent the entire length of the duct.
      After the procedures the ducts remained widely patent and arterial oxygen
      saturations remained above 80%. Complications of the procedures included
      perforation of a peripheral pulmonary artery and cardiac perforation, both caused
      by guide wire manipulation. Both babies died suddenly, one at five weeks, and the
      other at nine days after successful stenting of the duct. Both ducts were patent
      at necropsy; the exact cause of one death was not clearly defined, but the second
      seemed to be caused by pneumococcal septicaemia. CONCLUSIONS: Stenting of the
      arterial duct is technically feasible. It provides adequate palliation for
      neonates with pulmonary atresia at least in the short term and it seems to result
      in balanced, central perfusion of both pulmonary arteries. This preliminary
      report suggests that this previously untried technique may prove to be a
      promising and attractive alternative to neonatal aortopulmonary shunt operation.

PMID- 1372816
TI  - Eccrine syringofibroadenoma: a case report with analysis of cytokeratin
      expression.
AB  - A 56-year-old man presented with a 30-year history of a slowly enlarging lesion
      on the sole of his right foot. A biopsy showed an anastomosing network of small
      cuboidal cells with the formation of occasional sweat ductal lumina and a marked
      fibrovascular stroma. The histological findings were interpreted as consistent
      with the diagnosis of an eccrine syringofibroadenoma. Using immunohistochemistry
      all the tumour cells were positively stained by the pan-cytokeratin antibody Lu-5
      and an antibody to the cytokeratins 1/5/10/11. In addition the luminal ductal
      cells expressed cytokeratin 19 and CEA. Tumour cells were negative for
      cytokeratins 1, 7, 8, 13 and 18 and did not express vimentin and GCDFP-15. The
      results indicate that the eccrine syringofibroadenoma is differentiated towards
      the dermal eccrine duct.

PMID- 1372817
TI  - Palliation of bone metastases in prostate cancer. Hemibody irradiation or
      strontium-89?
AB  - The palliation of bone pain is a common clinical problem once metastatic prostate
      cancer has escaped from hormonal control. This retrospective study compares the
      results of treatment using hemibody irradiation (HBI) at the Royal Marsden
      Hospital (27 cases) with isotope therapy using the bone-seeking isotope strontium
      89 (89Sr) at Southampton General Hospital (51 cases). Prior to analysis patients
      were matched for potential prognostic factors (performance status, bone scan
      extent of disease, age, histology and duration of hormone response) to minimize
      the effect of treatment selection bias. Pain control assessed at 3 months was
      similar for HBI and matched 89Sr cases, with 63% and 52% respectively showing
      some benefit. Median survival was similar for these groups at 20 and 21 weeks
      respectively. The unmatched 89Sr group, which had more favourable prognostic
      factors, had a better outcome with 96% showing improvement in pain and with a
      median survival of 59 weeks. Subsequent univariate analysis demonstrated that
      performance status and extent of disease on bone scan were of overriding
      importance in determining outcome. Transfusion requirements were higher for the
      HBI group than for the matched 89Sr group (50% and 25% respectively) but other
      bone marrow toxicity was similar. Despite routine anti-emetic therapy 37% of
      patients treated with HBI had some nausea or vomiting. Although expensive, 89Sr
      appears as effective a treatment option as HBI. Response is most likely with
      either approach when patients have a good performance status and a limited extent
      of disease.

PMID- 1372818
TI  - The role of radiotherapy in carcinoma of the thoracic oesophagus: an audit of the
      Mount Vernon experience 1980-1989.
AB  - All 244 patients with carcinoma of the thoracic oesophagus registered at the
      Mount Vernon Centre for Cancer Treatment during the decade from 1 January 1980 to
      31 December 1989 have been audited. We have made a detailed analysis of 110 (45%)
      with localized disease considered unsuitable for surgery, who completed treatment
      solely by radiotherapy. The median survival of this group of patients was 8.2
      months (range 0.2-54 months). Dysphagia was improved by radiotherapy in 77.3% of
      cases, the median duration of relief was 24 weeks (range 0-208 weeks) and was
      maintained until death in 40%. Life table analysis showed that radical compared
      with less than radical regimens of radiotherapy gave significantly superior
      relief of dysphagia. This result is unlikely to be due to case selection.

PMID- 1372819
TI  - Metastasis to the penis from malignant melanoma: case report and review of the
      literature.
AB  - A case of metastatic malignant melanoma to the shaft of the penis is described
      and the literature reviewed to collate the incidence of primary sites which
      metastasize to the penis. Less than 260 cases of metastasis to the penis have
      been reported. Of these, 76% are from genitourinary primary sites and 17% are
      from gastrointestinal primary sites but only one case of metastatic melanoma to
      the penis has been previously reported. The described case presented with painful
      priapism while receiving combination chemotherapy for metastatic disease. A CT
      scan demonstrated a deposit in the left corpora cavernosa and needle aspiration
      cytology of a plaque attached to the shaft confirmed malignant melanoma cells.
      Palliation of the painful priapism was achieved by treatment with radiotherapy
      using large doses per fraction. Retrograde venous or lymphatic spread may have
      been the cause of a metastasis at this site. Prognosis is very poor.

PMID- 1372820
TI  - Maternal serum screening for Down's syndrome: the effect of routine ultrasound
      scan determination of gestational age and adjustment for maternal weight.
AB  - OBJECTIVE: To investigate the effect of using a routine ultrasound estimate of
      gestational age and maternal weight adjustment on maternal serum alpha
      fetoprotein (AFP), unconjugated oestriol (uE3) and human chorionic gonadotrophin
      (hCG) levels in antenatal screening for Down's syndrome. DESIGN: Women with a
      singleton pregnancy without Down's syndrome were screened using the three serum
      markers and an estimate of gestational age based on 'dates' (time since first day
      of the last menstrual period) and one based on an ultrasound scan examination was
      recorded together with maternal weight. SETTING: Women attending the Homerton
      Hospital, Hackney, for their antenatal care between February 1989 and January
      1990. SUBJECTS: 2113 women with a singleton pregnancy without Down's syndrome.
      RESULTS: The use of ultrasound to estimate gestational age (usually based on the
      biparietal diameter of the fetal skull) led to a significant reduction in the
      variance of each marker at a given week of pregnancy. The level of each marker
      was negatively associated with maternal weight, so that adjustment for weight
      also led to a reduction in variance. These data on gestational age and maternal
      weight, taken together with published data on pregnancies associated with Down's
      syndrome, indicate that the routine use of ultrasound to estimate gestational age
      will increase the detection rate from 58% to 67% while maintaining the false
      positive rate at 5%, or reduce the false-positive rate from 5.7% to 3.1% while
      maintaining the detection rate at 60%. Routine maternal weight adjustment for the
      serum marker levels was much less useful, increasing the detection rate by about
      0.5% for a given false-positive rate, or reducing the false-positive rate about
      0.1% for a given detection rate. CONCLUSION: An ultrasound gestational age
      estimate available at the time of Down's syndrome screening confers a substantial
      advantage to screening performance with a further small benefit resulting from
      maternal weight adjustment, which is worth adopting if it can be done without
      difficulty or extra cost.

PMID- 1372821
TI  - Why might maternal serum AFP be high in pregnancies in which the fetus is
      normally formed?

PMID- 1372822
TI  - Alpine rap. 1991 Arolla Workshop: from Receptor to Gene, sponsored by the
      European Molecular Biology Organization and the Swiss National Science
      Foundation. Arolla, Switzerland, August 25-September 1, 1991.

PMID- 1372823
TI  - Changes in the methylation pattern of the TCR zeta-chain gene correlate with its
      expression in T cells and developing thymocytes.
AB  - The tight regulation of T-cell gene expression during thymic ontogeny is
      essential to the development of a normal immune system. One set of
      developmentally regulated genes encodes the multicomponent T-cell antigen
      receptor (TCR). The zeta chain, a component of the TCR, has been shown to play
      important roles in signal transduction from antigen binding to T-cell activation
      and in transport of the TCR complex to the cell surface. In this study, we
      examine the regulation of zeta gene expression in murine T-cell hybridomas. In
      these cells, zeta expression is correlated with complex, but predictable, changes
      in the pattern of cytosine methylation of its gene. Some of these structural
      changes are identical to those observed in murine fetal thymocytes and correlate
      with the rapid alteration of zeta message seen in the thymus between days 15 and
      18 of gestation.

PMID- 1372824
TI  - Multiple binding sites for tetrahedral oxyanion inhibitors of bovine spleen
      purple acid phosphatase.
AB  - The theory of multiple inhibition kinetics has been extended to enzymes for which
      one inhibitor is noncompetitive and the other exhibits mixed inhibition. Plots of
      reciprocal velocity versus the concentration of either inhibitor at various fixed
      concentrations of the second inhibitor are predicted to give parallel lines if
      binding of the inhibitors is mutually exclusive and intersecting lines if the
      inhibitors interact at different sites on the enzyme. Application of this
      analysis to the purple acid phosphatase from bovine spleen in the presence of
      molybdate (a noncompetitive inhibitor) and phosphate (which exhibits mixed
      inhibition) results in parallel lines in the reciprocal velocity plots,
      indicating that phosphate and molybdate compete for a common site; since
      molybdate is a noncompetitive inhibitor, this site is inferred to be distinct
      from the site at which substrate binds and is hydrolyzed. Extension of these
      ideas suggests that phosphate ester substrates should be capable of binding to
      the molybdate-binding site as well as to the active site, and evidence for
      substrate inhibition at high substrate concentrations has been obtained. The
      implications of these findings for interpretation of previous spectroscopic
      studies of purple acid phosphatase complexes with tetrahedral oxyanions are
      discussed.

PMID- 1372825
TI  - DAPI (4',6-diamidino-2-phenylindole) binds differently to DNA and RNA: minor
      groove binding at AT sites and intercalation at AU sites.
AB  - The interaction of DAPI and propidium with RNA (polyA.polyU) and corresponding
      DNA (polydA.polydT) sequences has been compared by spectroscopic, kinetic,
      viscometric, Tm, and molecular modeling methods. Spectral changes of propidium
      are similar on binding to the AT and AU sequences but are significantly different
      for binding of DAPI. Spectral changes for DAPI with the DNA sequence are
      consistent with the expected groove-binding mode. All spectral changes for
      complexes of propidium with RNA and DNA and for DAPI with RNA, however, are
      consistent with an intercalation binding mode. When complexed with RNA, for
      example, DAPI aromatic protons signals shift significantly upfield, and the DAPI
      UV-visible spectrum shows significantly larger changes than when complexed with
      DNA. Slopes of log kd (dissociation rate constants) versus-log [Na+] plots are
      similar for complexes of propidium with RNA and DNA and for the DAPI-RNA complex
      and are in the range expected for an intercalation complex. The slope for the
      DAPI-DNA complex, however, is much larger and is in the range expected for a
      groove-binding complex. Association kinetics results also support an
      intercalation binding mode for the DAPI-RNA complex. The viscosity of polyA.polyU
      solutions increases significantly on addition of both propidium and DAPI, again
      in agreement with an intercalation binding mode for both molecules with RNA.
      Molecular modeling studies completely support the experimental findings and
      indicate that DAPI forms a very favorable intercalation complex with RNA. DAPI
      also forms a very stable complex in the minor groove of AT sequences of DNA, but
      the stabilizing interactions are considerably reduced in the wide, shallow minor
      groove of RNA. Modeling studies,thus,indicate that DAPI interaction energetics
      are more favorable for minor-groove binding in AT sequences but are more
      favorable for interaction in RNA.

PMID- 1372826
TI  - Folate binding protein from kidney brush border membranes contains components
      characteristic of a glycoinositol phospholipid anchor.
AB  - A number of cell surface proteins have been shown to be anchored to the plasma
      membrane by a covalently attached glycoinositol phospholipid (GPL) in amide
      linkage to the C-terminus of the mature protein. We applied several criteria to
      establish that folate binding protein (FBP) in brush border membranes of rat
      kidney contains a GPL anchor. Brush border membranes were isolated and labeled
      with [3H]folate, and the complex of FBP and [3H]folate was shown to be released
      to the supernatant by incubation with purified bacterial phosphatidylinositol
      specific phospholipase C (PIPLC) but not by incubation with a purified bacterial
      phosphatidylcholine-specific phospholipase C. The FBP-[3H]folate complex both in
      crude extracts and after FBP purification by ligand-directed affinity
      chromatography interacted with Triton X-114 micelles, and prior incubation with
      PIPLC prevented this detergent interaction. Individual residues characteristic of
      GPL anchors were found to be covalently associated with FBP following
      polyacrylamide gel electrophoresis in sodium dodecyl sulfate. These included
      glucosamine and ethanolamine, which were radiolabeled by reductive methylation
      and identified by chromatography on an amino acid analyzer, and inositol
      phosphate, which was inferred by Western blotting with an anti-CRD antisera. This
      antisera gave positive immunostaining only after FBP had been cleaved by PIPLC, a
      reliable diagnostic of a GPL anchor. The relationship between GPL-anchored FBP in
      biological membranes and soluble FBP in biological fluids also is discussed.

PMID- 1372827
TI  - Ca2+/calmodulin-dependent NO synthase type I: a biopteroflavoprotein with
      Ca2+/calmodulin-independent diaphorase and reductase activities.
AB  - NO synthase (NOS; EC 1.14.23) catalyzes the conversion of L-arginine into L
      citrulline and a guanylyl cyclase-activating factor (GAF) that is chemically
      identical with nitric oxide or a nitric oxide-releasing compound (NO). Similar to
      the other isozymes of NOS that have been characterized to date, the soluble and
      Ca2+/calmodulin-regulated type I from rat cerebellum (homodimer of 160-kDa
      subunits) is dependent on NADPH for catalytic activity. The enzyme also possesses
      NADPH diaphorase activity in the presence of the electron acceptor nitroblue
      tetrazolium (NBT). We investigated the requirements of NOS and its content of the
      proposed additional cofactors tetrahydrobiopterin (H4biopterin) and flavins,
      further characterized the NADPH diaphorase activity, and quantified the NADPH
      binding site(s). Purified NOS type I Ca2+/calmodulin-independently bound the
      [32P]2',3'-dialdehyde analogue of NADPH (dNADPH), which, at near Km
      concentrations during 3-min incubations was utilized as a substrate and at higher
      concentrations or after prolonged incubations and cross-linking inhibited NOS
      activity. The NADPH diaphorase activity was Ca2+/calmodulin-independent, required
      higher NADPH concentrations than NOS activity, and was affected by dNADPH to a
      lesser degree. Divalent cations interfered with the diaphorase assay. Per dimer,
      native NOS contained about 1 mol each of H4biopterin, FAD, and FMN, classifying
      it as a biopteroflavoprotein, and incorporated 1 mol of dNADPH. No
      dihydrobiopterin (H2biopterin), biopterin, or riboflavin was detected. These
      findings suggest that NOS may share cofactors between two identical subunits via
      high-affinity binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372828
TI  - Structural and functional characterization of the phosphorylated adipocyte lipid
      binding protein (pp15).
AB  - A substrate for the insulin receptor kinase in 3T3-L1 adipocytes has previously
      been identified as the adipocyte lipid-binding protein (ALBP, also known as aP2
      or p15). We have characterized the effect of tyrosyl phosphorylation on ALBP
      structure and ligand-binding properties. Phosphorylated ALBP (phospho-ALBP) was
      isolated by a combination of gel filtration, anion exchange chromatography, and
      immunoaffinity chromatography on anti-phosphotyrosine agarose. Circular dichroic
      spectroscopy indicated that the phosphoprotein was similar in structure to native
      ALBP. Phospho-ALBP exhibited a slight decrease in calculated alpha-helical
      content which was compensated for by an increase in beta-sheet structure. The
      wavelength yielding maximum tryptophan fluorescence was unaltered by
      phosphorylation (334 +/- 1 nm). However, the concentration of guanidine HCl
      yielding 50% denaturation was 1.43 M for ALBP and 0.92 M for phospho-ALBP. The
      delta Goapp was 3.87 and 3.25 kcal mol-1 for ALBP and phospho-ALBP, respectively,
      suggesting that phosphorylation destabilized the protein. To assess the binding
      characteristics of the phosphoprotein, a long-chain fatty acid affinity column
      was synthesized to which native ALBP specifically bound. In contrast, phospho
      ALBP showed little or no affinity for the column. Furthermore, phosphorylation
      virtually abolished binding of the fluorescent fatty acid analogue 12-(9
      anthroyloxy)oleic acid. Fatty acid binding activity was recovered (approximately
      60%) upon dephosphorylation with protein tyrosine phosphatase. The structural
      studies, coupled with the crystal structure of the apoprotein, indicate that the
      dramatic reduction in binding affinity is likely a result of steric hindrance in
      the binding cavity or of electrostatic interactions of the phosphoryl group with
      the fatty acid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372829
TI  - Vitronectin diversity in evolution but uniformity in ligand binding and size of
      the core polypeptide.
AB  - We isolated vitronectins from the plasma or sera of 14 animal species including
      mouse and rat by heparin affinity chromatography. They cross-reacted with anti
      vitronectin antibody and their amino terminal sequences showed strong homology.
      They also promoted spreading of BHK cells and were bound to heparin and collagen
      in the same way. Therefore, these properties appear to be essential for
      vitronectin function. However, the apparent molecular weights of these
      vitronectins varied considerable from 59 to 78 kDa in sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE). In addition, the number of bands
      also varied from 1 to 3. To search for the uniformity of vitronectin polypeptide,
      vitronectins were deglycosylated and examined by Ferguson plot analysis. The size
      of the polypeptide portion of vitronectins was estimated to range from 40 to 57
      kDa which was 19-26 kDa smaller than original values. Supposing a possible
      cleavage site at 5-13 kDa far from the carboxyl terminus, all vitronectin
      polypeptides were speculated to be synthesized de novo in the size range of 50-57
      kDa. Proteins reacting with anti-vitronectin antibody were also detected on the
      immunoblot of 13 more species including Drosophila and Physarum. Almost all of
      these vitronectin-like proteins showed marked species-specific variations in
      their apparent molecular weights from 51 to 96 kDa in SDS-PAGE.

PMID- 1372830
TI  - Separation and characterization of isoforms of DT-diaphorase from rat liver
      cytosol.
AB  - Rats were treated with 3-methylcholanthrene (MC) and DT-diaphorase from liver was
      partially purified on an azodicoumarol-Sepharose 6B column and applied to an FPLC
      chromatofocusing column in order to resolve isoforms. Six peaks showing
      significant DT-diaphorase activity were eluted from this column with a pH
      gradient between 7.30 to 4.80. The amino acid compositions of the two major peaks
      (II and VIb) were found to be nearly identical, suggesting existence of isoforms
      rather than isozymes of DT-diaphorase. The isoforms of DT-diaphorase showed broad
      substrate specificities towards four different quinones (menadione, vitamin K-1,
      benzo(a)pyrene 3,6-quinone and cyclized-dopamine ortho-quinone), although
      quantitative differences in the specific activities were also found. All isoforms
      are glycoproteins but contain different carbohydrates. Thus isoform II reacts
      with biotinylated lectins which are specific for N-acetylgalactosamine, mannose,
      fucose and galactosyl(beta-1,3)N-acetylgalactosamine, while isoform VIb reacts
      only with biotinylated lectins specific for mannose and N-acetylgalactosamine.
      Separation of DT-diaphorase isoforms from control rat liver cytosol using FPLC
      chromatofocusing revealed that the induction of the isoforms is not uniform,
      since isform II was not found and the major isoform was composed of three peaks,
      whereas the major isoform of DT-diaphorase from liver cytosol of rats treated
      with 3-methylcholanthrene was composed of only two peaks.

PMID- 1372831
TI  - Cyclic AMP produces desensitization of prostacyclin and adenosine A2 receptors in
      hybrid cell lines but does not affect Gs function.
AB  - Prostacyclin and adenosine A2 receptors stimulate adenylate cyclase activity in
      the related somatic hybrid cell lines NG108-15 and NCB20. The role of cAMP in the
      desensitization of these receptors has been examined. Pretreatment for 17 h with
      forskolin or 8-bromo-cAMP had the same effect in both cell lines. There was no
      change in the response to sodium fluoride or forskolin, suggesting that the
      function of Gs and adenylate cyclase were unaffected by increased levels of cAMP.
      Receptor responses were affected however; the maximum response to N
      ethylcarboxamidoadenosine (an A2 receptor agonist) was reduced by 30-40%, there
      was a small but consistent shift to the right of the dose-response curve for
      iloprost (a stable analogue of prostacyclin) and [3H]iloprost binding studies
      revealed a loss of prostacyclin receptors. However, the loss of receptor
      responsiveness was much smaller than that which occurs following pretreatment
      with prostacyclin or adenosine A2 receptor agonists (Keen et al. (1989) Biochem.
      Pharmacol. 38, 3827-3833; Kelly et al. (1990) Br. J. Pharmacol. 99, 309-316)
      suggesting that cAMP may not play a major role in agonist mediated
      desensitization.

PMID- 1372832
TI  - Immunohistochemical detection of porcine rotavirus using immunogold silver
      staining (IGSS).
AB  - Immunogold silver staining (IGSS) was applied for the detection of porcine group
      A rotavirus in formalin-fixed paraffin-embedded tissue sections of small
      intestine. Prior to the application of IGSS, the reactivity of protein A-gold as
      a marker was tested with group-specific antiserum in immunogold electron
      microscopy. Immune aggregates were intensely and specifically labeled with the
      gold complex. Application of IGSS to tissue sections resulted in specific dark
      staining of villous enterocytes infected by group A rotavirus. This method also
      proved effective for the detection of rotaviral antigen in infected cultured
      cells. The IGSS method may be suitable for routine diagnostic detection of
      rotaviral infections and may have application for detection of other viral
      pathogens of veterinary importance.

PMID- 1372833
TI  - Phenotypic and clinical heterogeneity of CD56-positive acute nonlymphoblastic
      leukemia.
AB  - The precise phenotype and clinical course are described of a subgroup of acute
      nonlymphoblastic leukemias (ANLL) expressing the NK-cell differentiation antigen
      CD56. As previously reported, CD56+ leukemias occurred in a frequency of about
      20% of ANLL cases showing clinical and immunophenotypical heterogeneity. Carrying
      various myelomonocytic markers, all cases were diagnosed to be of nonlymphoid
      origin. Positive or negative expression of CD34 allowed us to distinguish two
      major subtypes of CD56+ leukemias representing immature and more differentiated
      cells carrying further differentiation antigens (CD14 and/or CD15) of the
      myelomonocytic lineages. These phenotypes correlated with the M0, M2, M4, and M5
      leukemias of the FAB classification.

PMID- 1372834
TI  - The use of fluorescent nuclear dyes for the study of blood vessel structure and
      function: novel applications of existing techniques.
AB  - We have used nuclear fluorescent dyes to develop a technique for the study of
      vascular structure and function. Nuclear stained blood vessels, viewed with the
      appropriate filter sets, can be studied in great detail. Only the nuclei of the
      cells which form the walls are visible and so their positions relative to one
      another as well as their viability can be quickly assessed. The dyes are not
      toxic, therefore when the vessel contracts or relaxes, the changes in position of
      the nuclei can be monitored. In this paper we describe two original applications
      of fluorescent nuclear dyes in vascular research.

PMID- 1372835
TI  - Protein structural effects in gas phase ion/molecule reactions with diethylamine.
AB  - The relationship between gas-phase protein structure and ion/molecule reactivity
      is explored in comparisons between native and disulfide-reduced aprotinin,
      lysozyme, and albumin. Reactions are performed in the atmospheric-pressure inlet
      to a quadrupole mass spectrometer employing a novel capillary interface-reactor.
      In reactions with equal concentrations of diethylamine, multiply protonated
      molecules generated by electrospray ionization (ESI) of 'native' proteins shifted
      to lower charge states than did multiply protonated molecules from ESI of the
      disulfide-reduced counterparts, suggesting that the disulfide-reduced protein
      ions are less reactive than native protein ions of the same charge state.
      Differences in reactivity may arise from protonation of different amino acid
      residues and/or differences in the proximities of charge sites in the two
      molecules. These results suggest that the reactivity of multiply charged proteins
      can be significantly affected by their gas-phase structure.

PMID- 1372836
TI  - Chromaffin cell transplants for alleviation of chronic pain.
AB  - Treatment of intractable pain with parenteral, subarachnoid, or epidural
      narcotics is often unsatisfactory due to tolerance and other systemic
      complications that accompany increasing dosages of these drugs. Other
      disadvantages include the potential infections with implantable pumps and the
      inconvenience of repeated narcotic administration. During the past several years,
      studies at the author's laboratory indicated that transplantation of adrenal
      medullary tissue or isolated chromaffin cells into the spinal subarachnoid space
      can significantly reduce pain in several rodent models without resulting in
      development of tolerance. Adrenal medullary chromaffin cells were selected
      because they produce high levels of both opioid peptides and catecholamines,
      agents that independently, and possibly synergistically, reduce pain when
      injected locally into the spinal subarachnoid space. The adrenal medullary
      transplants survive for prolonged periods, and continue to produce high levels of
      both catecholamines and met-enkephalin. These transplants reduce pain in two
      rodent chronic pain models, an arthritis model and a peripheral neuropathy model,
      both of which closely resemble human chronic pain syndromes. The success of the
      animal studies has led to initiation of human clinical trials in patients with
      chronic cancer pain; results are promising.

PMID- 1372837
TI  - Mental health and developmental problems of children in poverty.

PMID- 1372838
TI  - Integrin expression by human articular chondrocytes.
AB  - Expression of integrins, a family of cell adhesion proteins, by human articular
      cartilage chondrocytes in vivo has been studied by immunohistological techniques
      using cryostat sections and a panel of anti-integrin monoclonal antibodies.
      Chondrocytes strongly expressed beta 1 and alpha 5 integrin subunits, known to
      form the classical fibronectin receptor, VLA-5, strongly. alpha 1 was expressed
      more weakly and variably; alpha 3 was expressed by occasional cells only.
      Chondrocytes did not express beta 2, beta 3 or other integrin alpha subunits
      tested.

PMID- 1372839
TI  - Constitutional translocation (8;13) in a patient with non-Hodgkin's lymphoma.
AB  - We report a case of non-Hodgkin's lymphoma in a 16-year-old male, whose
      peripheral white blood cells have a t(8;13)(q24;q14). There are no previous
      reports that describe this association. Although the tumor cells were not
      studied, we discuss the possible link between this finding and the development of
      the malignant lymphoma.

PMID- 1372840
TI  - Marrow fibrosis associated with a Philadelphia chromosome.
AB  - Three patients had marked marrow fibrosis and an apparent Philadelphia (Ph)
      chromosome. Hematologic, cytogenetic, and molecular studies demonstrated the
      heterogeneity of such cases, including the first example of clinically typical
      myelofibrosis (MF) associated with a bcr gene rearrangement characteristic of
      chronic myelogenous leukemia (CML).

PMID- 1372841
TI  - Potentiation of transmembrane signaling by cross-linking of antibodies against
      the beta chain of the T cell antigen receptor of JURKAT T cells.
AB  - Three monoclonal antibodies (mAb) 2D1, 3B9, and 3B12 were produced by immunizing
      BALB/c mice with JURKAT cells. These mAb induce comodulation of the TCR/CD3
      complex expressed on JURKAT cells, but do not react with the CD3- JURKAT variant,
      J.RT3.T3.1. Immunoprecipitation studies with detergent-solubilized JURKAT cell
      lystes indicate that these mAb react with proteins having characteristics of the
      TCR molecules. Their low reactivity with peripheral blood mononuclear cells
      (PBMC) and lack of reactivity with other CD3+ T cell lines suggest that they may
      be anti-idiotypic mAb. Results from binding inhibition assays, reactivity with
      PBMC, and generation of transmembrane signals suggest that these three anti-TCR
      mAb recognized different epitopes on the TCR beta chain of JURKAT cells. Although
      the three mAb are capable of inducing the production of inositol phosphates and
      cytosolic free Ca2+ increase in JURKAT cells, their stimulatory capacities vary
      and are lower than that observed by anti-CD3 antibody (OKT3) stimulation.
      However, crosslinking these mAb with rabbit antimouse immunoglobulins potentiates
      the stimulatory response to comparable levels induced by OKT3. These mAb could be
      useful as tools to study V beta 8+ T cells in relation to antigen-specific
      activation.

PMID- 1372842
TI  - CD7 augments T cell proliferation via the interleukin-2 autocrine pathway.
AB  - The role of CD7, a T cell differentiation antigen, in T cell function is not
      known at present; this study evaluates the effect of anti-CD7 mAb in PMBC
      cultures activated with suboptimal concentrations of lectins, antigens, and anti
      CD3 mAb. We found that the inclusion of anti-CD7 resulted in increased IL-2
      production and IL-2R-alpha expression in these cultures. H-7, a protein kinase C
      (PKC) inhibitor, and genistein, a protein tyrosine kinase (PTK) inhibitor,
      significantly suppressed the proliferation of T cells in comitogenic assays. This
      suggested that the comitogenic effect mediated by CD7 molecule involved both the
      PKC and the PTK pathways of T cell activation. These drugs appeared to affect the
      CD7-mediated effects by inhibiting the IL-2 autocrine pathway, especially the up
      regulation of IL-2R-alpha since inhibition was not relieved with exogenous rIL-2.
      Taken together, our results suggest that CD7 augments T cell function by up
      regulating IL-2R-alpha expression and IL-2 production via multiple pathways of
      protein phosphorylation.

PMID- 1372843
TI  - Synthetic peptides representing sequence 39 to 59 of rat V beta 8 TCR fail to
      elicit regulatory T cells reactive with V beta 8 TCR on rat encephalitogenic T
      cells.
AB  - Subpathogenic doses of syngeneic autoreactive T cells protect experimental
      animals against associated autoimmune disease. Preferential use of the TCR of
      encephalitogenic T cells suggests that this molecule serves as the target for
      immunoregulation in experimental autoimmune encephalomyelitis (EAE). Whether
      peptides derived from the V beta 8 of the rat TCR elicit regulatory T cells and
      produce the same vaccinating effect against EAE as do whole T cells remains
      unknown. Here we show that immunization of Lewis rats with V beta 8(39-59), a
      peptide representing residues 39 to 59 of the rat V beta 8 TCR, does not induce
      the production of regulatory T cells reactive to the intact TCR V beta 8
      containing this sequence. Moreover, animals that had recovered from both actively
      induced EAE and transferred EAE did not generate regulatory T cells that
      recognized the V beta 8(39-59) peptide. Further, transfusion of large doses of
      peptide-specific T cells did not protect the animals from EAE. Our results
      suggest that the V beta 8(39-59) peptide may comprise so-called cryptic epitopes,
      which function as immunogens only when dissociated from large protein complexes.

PMID- 1372844
TI  - An antigen expressed by avian neuronal cells is also expressed by activated T
      lymphocytes.
AB  - A monoclonal antibody, anti-BEN, initially characterized by its reactivity with
      an epitope present on the surface of avian bursa epithelial cells and neurons,
      also reacts with membrane molecules on some hemopoietic cells. In this study we
      examine BEN expression on lymphoid cells in thymus, spleen, and blood. We
      demonstrate that BEN is an activation antigen on mature T lymphocytes. It is not
      expressed on peripheral blood or splenic lymphocytes, but following mitogenic or
      allogeneic stimulation of blood lymphocytes it appears rapidly on a T cell
      subpopulation in parallel with the appearance of IL-2 receptors. BEN is also
      expressed on III-C5 cells, an avian IL-2-dependent permanent T cell line, and on
      immature CD4+CD8+ thymocytes. BEN is not expressed by resting or actively
      proliferating B cells. Biochemical analyses of the BEN protein on T lymphoblasts
      shows that the molecule is similar in size to the BEN molecules on bursa
      epithelial cells and on neurons. The physicochemical properties of the BEN
      protein and its tissue distribution differs from other known avian and mammalian
      T cell activation markers, differentiation antigens, and integrins. Thus BEN is a
      novel marker of activated T cells in birds.

PMID- 1372845
TI  - Influence of feeding paradigm in rats on temporal pattern of: II. Brain
      serotoninergic and catecholaminergic systems.
AB  - The relationship between the feeding paradigm (single diet versus food selection)
      and central idoleamines and catecholamines was studied. Temporal patterns of the
      brain parameters in response to presentation of a single diet of fixed
      composition (20% casein) or a choice between two isocaloric diets (0% and 60%
      casein) for 2 weeks under 8-h feeding cycles during the dark phase were measured
      in adult Sprague-Dawley rats. Groups of animals were then killed at the beginning
      and at 2-h intervals throughout the feeding period. The distribution and the
      temporal pattern of variation of the serotoninergic and the catecholaminergic
      parameters studied were significantly affected by the diet paradigms used. A
      different neurochemical equilibrium was observed before food intake and was
      characterized by a central serotoninergic predominance in subjects having a
      dietary selection experience but a central catecholaminergic predominance in
      animals adapted to a single diet. Hypothalamic and extrahypothalamic
      serotoninergic and catecholaminergic systems were found to intervene in an
      interdependent way, sometimes antagonistic according to the feeding paradigm and
      the related temporal changes in energy intake and macronutrient selection. These
      results suggest that central serotoninergic and catecholaminergic systems are
      influenced by the diet paradigm and display characteristic patterns of temporal
      variations during the feeding cycle. The feeding paradigm, per se, should then be
      considered as a potential synchronizer of central biological rhythms of
      monoamines, which in turn may affect food intake and appetite for macronutrients.

PMID- 1372846
TI  - Assessing and diagnosing developmental disorders that are not evident at birth:
      parental evaluations of intake procedures.
AB  - Studies of parental satisfaction with the way in which diagnostic information is
      imparted have generally focused on conditions that are evident from birth.
      Diagnostic disclosure for disorders in which the onset is later, and less readily
      identifiable, has received less attention. The present study investigated
      parents' views of diagnostic procedures for children whose developmental delays
      only became apparent as they grew older. The degree of satisfaction was related
      to the type of diagnosis given but 2 weeks after the assessment 87% of parents
      described themselves as being very or fairly satisfied. However, levels of
      satisfaction were lower at a later follow-up than they had been initially.
      Moreover, several specific aspects of the assessment fell short of the ideal
      model and parents offered a number of practical and cost-effective suggestions as
      to how these could be remedied. These ranged from ways in which pre-assessment
      procedures could be made more useful, how diagnostic information should be
      presented and how the physical setting could be improved.

PMID- 1372847
TI  - Induction of ventricular fibrillation versus monomorphic ventricular tachycardia
      during programmed stimulation. Role of premature beat conduction delay.
AB  - BACKGROUND: Premature stimuli can cause ventricular fibrillation (VF) during
      electrophysiological testing. The electrophysiological correlations associated
      with the onset of VF were evaluated in 40 patients who had this rhythm induced
      during programmed ventricular stimulation. These parameters were compared with
      those observed in 51 patients who had inducible sustained monomorphic ventricular
      tachycardia (VT) and 45 patients who had no inducible sustained ventricular
      tachyarrhythmias. METHODS AND RESULTS: Shortest premature coupling intervals for
      S2, S3, and S4 at induction of tachycardia or before achieving refractoriness,
      corresponding conduction latencies (defined as the time from the premature
      stimulus to the upstroke of the depolarization wave front recorded 35 mm away
      from the stimulation site), and ventricular activation times (defined as the time
      from the premature stimulus to the end of the depolarization wave) were compared.
      The mean coupling intervals were longest in the inducible VT patients: 300 +/-
      30, 254 +/- 57, and 228 +/- 32 msec for S2, S3, and S4, respectively. In the
      inducible VF group, the coupling intervals were 260 +/- 37, 208 +/- 20, and 213
      +/- 30 msec. In the group with no inducible VT or VF, these coupling intervals
      were 251 +/- 24 (p less than 0.01 versus inducible VT group), 209 +/- 27 (p less
      than 0.001 versus inducible VT group), and 194 +/- 21 msec (p less than 0.05
      versus inducible VT and VF groups). The coupling interval of the last premature
      extrastimulus was above 200 msec in 70% of the patients in whom VF was induced.
      The largest increases in latency and activation times were recorded in patients
      in whom VF was induced. The cumulative increase in latency, defined as increased
      conduction time from baseline, summed for all the premature stimuli was also the
      greatest at initiation of VF. In contrast, the smallest increases in these
      parameters were noted in the patients with no inducible VT or VF. Measurements of
      total activation time yielded similar results as those recorded for latencies.
      The most important parameters distinguishing the VT patient population from the
      other two groups were the low ejection fractions and the longer coupling
      intervals at which VT was induced, whereas in the VF group, the most important
      discriminating factor was cumulative activation time. Sixty-three percent of the
      inducible VF patients presented with abnormal hearts (myocardial infarction or
      cardiomyopathy), whereas 88% of the inducible VT patients had abnormal hearts. In
      contrast, only 25% of the patients in whom no arrhythmia was induced presented
      with abnormal hearts. Mean ejection fraction was 32 +/- 15% for the inducible VT
      group, 45 +/- 13%* for the inducible VF group, and 51 +/- 17%* for patients with
      no inducible VT/VF (*p less than 0.001 versus VT). CONCLUSIONS: The results
      suggest that 1) initiation of ventricular tachycardia during programmed
      ventricular stimulation occurs with minimal conduction latency; 2) because of the
      large overlap in coupling intervals where VF or VT were induced, a single
      coupling interval cannot be recommended to adequately separate these groups; and
      3) induction of VF was preceded by increased latency and prolongation of the
      local activation time. These parameters should not be allowed to prolong if VF is
      to be avoided during programmed stimulation. In addition, 4) the initiation of VF
      during electrophysiological studies is often associated with the presence of
      structural heart disease; such structural disease may promote conduction latency
      and the development of VF.

PMID- 1372848
TI  - Imaging of vascular injury with 99mTc-labeled monoclonal antiplatelet antibody
      S12. Preliminary experience in human percutaneous transluminal angioplasty.
AB  - BACKGROUND: To evaluate the in vivo safety, biodistribution, and diagnostic
      accuracy of a monoclonal Fab' antibody (S12) that is specific for the platelet
      membrane glycoprotein (GMP-140) expressed during platelet activation at vascular
      injury sites, 11 peripheral percutaneous transluminal angioplasty (PTA) patients
      (age, 61 +/- 8 years) with severe vascular disease had serial 99mTcS12
      radionuclide imaging at 5 and 90 minutes, 4-6 hours, and 20-24 hours after a
      total of 23 angiographically successful PTA procedures. No acute allergic
      reactions or hematologic toxicity occurred. METHODS AND RESULTS: The average PTA
      percent angiographic diameter stenosis (DS) at all 23 sites decreased from 85 +/-
      12% to 12 +/- 11%, with a mean before-to-after-PTA change of 73 +/- 14% (p less
      than 0.01). The mean radionuclide image-derived ratio of 99mTc S12 activity in
      PTA versus contralateral non-PTA arterial segments for all angioplasty sites was
      1.6 +/- 0.5. Vascular 99mTc S12 antibody activity was qualitatively evident in
      the majority (78%) of PTA sites at 4-6 hours after injection. 99mTc S12 target-to
      background (muscle) ratio equaled 2.3 +/- 0.6 at PTA sites. Nine PTA sites (39%)
      had residual 99mTc S12 activity at 24 hours after injection (mean PTA site-to
      contralateral artery ratio, 1.5 +/- 0.4). The mean vascular 99mTc S12 activity
      ratios in 10 procedurally complicated (defined as extensive dilation [greater
      than 2 cm] or grade I or greater arterial dissection) and 13 uncomplicated PTA
      segments were 1.9 +/- 0.5 versus 1.2 +/- 0.1, respectively (p less than 0.01).
      The associated before-to-after-PTA angiographic improvement was significantly
      less in procedurally complicated PTA sites (66 +/- 12% versus 80 +/- 12% DS; p
      less than 0.01). CONCLUSIONS: 99mTc S12 activity is significantly increased at
      angiographically patent PTA sites that are procedurally complicated and are
      associated with less significant before-to-after-PTA angiographic improvement.
      99mTc S12 monoclonal Fab' antibody imaging permits noninvasive identification of
      local vascular platelet activation resulting from angioplasty balloon injury in
      humans.

PMID- 1372849
TI  - Repetitive electrical activity of the muscle membrane induced in chloride-free
      medium.
AB  - 1. Superficial fibres of frog skeletal muscle were electrically stimulated in
      Ringer solution where the chloride content had been replaced by various weakly
      permeant anions. Changes of the membrane potential were recorded at three
      different time scales. The complex response was initiated by a volley of fast
      repetitive action potentials (10-20 ms cycle length) superimposed on the
      ascending phase of a transient depolarization to -35 mV. The transient
      depolarization was followed by a membrane potential oscillation (0.3-0.6 s cycle
      length). The parameters of the volley and membrane potential oscillation were not
      greatly affected by the substituent anion. 2. The transient depolarization was
      fully abolished by tetrodotoxin (3 mumol/L), but left unaffected by nifedipine (5
      mumol/L), or by the replacement of extracellular Ca for Ni or Co.
      Tetraethylammonium (20-40 mmol/L) increased the duration and amplitude of the
      transient depolarization. The shape of transient depolarization was uniform in a
      given fibre, in spite of its marked variability under different experimental
      conditions. 3. Single outward current pulses applied in chloride-free solution
      containing tetraethylammonium (20-40 mmol/L) evoked prolonged depolarizations to
      positive membrane potentials accompanied by increases in the specific membrane
      conductance. This slow response, which was also frequently observed in the
      absence of TEA, was mediated by Ca ions, as it was insensitive to tetrodotoxin (3
      mumol/L) but abolished by nifedipine (10 mumol/L). 4. Two populations of the
      muscle fibres were observed during the slow response. Some fibres repolarized
      completely, while others failed to produce complete repolarization but formed a
      plateau between -20 and -30 mV, lasting for several minutes. When the external K
      concentration was abruptly increased to 5 or 10 mmol/L during the plateau of the
      slow response, repolarization and increase in membrane conductance were observed.
      5. In muscle fibres, having osmotically disrupted T-system, the duration of
      transient depolarization was in the range of minutes, in contrast to the range of
      seconds observed in intact fibres. The volley was preserved in glycerol treated
      fibres, however, the baseline of discharges was close to the resting potential
      and the rate of depolarization of the baseline was significantly less in glycerol
      treated than in intact fibres. 6. These results are consistent with the existence
      of a second stable membrane potential level in skeletal muscle between -40 and 
      30 mV. The depolarization and repolarization during the membrane potential
      oscillation and transient depolarization can be regarded as a partial or full
      transition, respectively, between these two stable membrane potential levels,
      possibly due to the conductance changes of the inward rectifier K
      channels.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1372850
TI  - Role of impairment of blood supply of the femoral head in the pathogenesis of
      idiopathic osteonecrosis.
AB  - To investigate the role of blood supply in the pathogenesis of idiopathic
      osteonecrosis of the femoral head, superselective angiography of the medial
      circumflex artery was performed. Sixteen hips with early stage osteonecrosis
      diagnosed by bone scintigraphy were studied, as were 22 contralateral normal hips
      (from unilateral cases) and 22 roentgenographically and scintigraphically normal
      hips in patients who had been administered corticosteroids. All hips demonstrated
      abnormal superior retinacular arteries in the extraosseous area, and small
      arteries penetrated 14 hips with early stage osteonecrosis. Abnormal findings
      were noted in 17 of 22 contralateral normal hips and in 20 of 22 normal hips with
      corticosteroid administration. Follow-up roentgenographic analysis showed that
      the hips with small arterial penetration most often developed osteonecrosis.
      There were two important findings: (1) The blood supply of the superior
      retinacular arteries from the extraosseous site was impaired. (2)
      Revascularization was observed not only in hips with early stage osteonecrosis
      but also in contralateral normal hips and normal hips with corticosteroid
      therapy. Osteonecrosis is not necessarily a consequence of a single episode of
      impairment of blood supply of the femoral head but that of a repetitive episode
      if interruption of revascularization.

PMID- 1372851
TI  - Relationship of urinary serotonin excretion to cigarette smoking and respiratory
      symptoms. The Normative Aging Study.
AB  - The relationship of 2-h urinary excretion of serotonin and 5-hydroxyindoleacetic
      acid (5-HIAA) to cigarette smoking and respiratory symptoms was examined among
      631 male participants in the Normative Aging Study (age range, 44 to 85 years).
      The amount of serotonin excreted in urine was inversely related to age (p less
      than 0.001). Mean 2-h excretion of serotonin varied from 8.01 micrograms for men
      40 to 49 years of age to 5.84 micrograms for those 70 years of age or over. No
      clear relationship was evident between the amount of 5-HIAA excreted in urine and
      age. After adjustment for age, current smokers were found to excrete more
      serotonin (p less than 0.001) and 5-HIAA (p = 0.001) than never smokers. Former
      smokers did not differ significantly from never smokers in these respects. After
      adjustment for age and smoking status in a multivariate model, chronic cough was
      a significant predictor of serotonin excretion (p = 0.005); chronic cough was
      less predictive of 5-HIAA excretion (p = 0.07). Other respiratory symptoms were
      unrelated to urinary excretion of serotonin and 5-HIAA. The mechanisms underlying
      the observed relationships of urinary serotonin and 5-HIAA excretion to smoking
      and to chronic cough and their potential relevance to chronic bronchitis remain
      to be determined.

PMID- 1372852
TI  - [The palliative measures in esophageal carcinoma].

PMID- 1372853
TI  - [The palliative measures in esophageal carcinoma].

PMID- 1372854
TI  - Progress in the 1980s and new directions in the 1990s with hypertension
      management. From the stepped-care approach to the individualised programme in
      hypertension treatment and control.

PMID- 1372855
TI  - Interferon gamma-1b. A review of its pharmacology and therapeutic potential in
      chronic granulomatous disease.
AB  - Chronic granulomatous disease is a group of rare x-linked or autosomal genetic
      disorders of the phagocytic NADPH oxidase system involved in host defence against
      various microorganisms. It is manifested by a common phenotype consisting of
      recurrent serious, life-threatening infection and granuloma formation. Following
      the finding that interferon gamma-1b (IFN gamma-1b) can potentiate phagocyte
      activity in some other disease states as well as restoring defective phagocyte
      NADPH oxidase system activity in at least some patients with chronic
      granulomatous disease, a large-scale placebo-controlled trial was undertaken with
      IFN gamma-1b in patients with chronic granulomatous disease. Long term treatment
      with a therapeutic dosage of IFN gamma-1b produced a significant reduction in the
      incidence of serious clinical events necessitating hospitalisation. The relative
      risk of serious infection and the number of days in hospital were each reduced by
      about two-thirds, and the mean duration of hospital stay by about one-third in
      those who did experience infection. The greatest therapeutic benefit was found in
      patients aged less than 10 years, but all patients were improved regardless of
      age, sex, use of prophylactic antibiotics or genetic pattern of inheritance. The
      drug was well tolerated with the commonest adverse effects (e.g. fever, headache,
      chills, injection site erythema) usually being mild, transient, and relieved by
      symptomatic treatment. IFN gamma-1b therefore provides an effective and well
      tolerated therapy for patients with chronic granulomatous disease, offering an
      important clinical advance in the treatment of this rare genetic disorder by
      improving the prognosis of its serious and life-threatening infectious sequelae.

PMID- 1372856
TI  - Fosinopril. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic potential in essential hypertension.
AB  - Fosinopril is a phosphinic acid prodrug which, after oral administration,
      undergoes rapid hydrolysis to its active diacid, the angiotensin converting
      enzyme (ACE) inhibitor fosinoprilat. Unlike other ACE inhibitors, fosinoprilat
      has a compensatory dual route of elimination and is cleared by the liver and
      kidneys. Thus, in patients with diminished renal function increased hepatic
      clearance of fosinoprilat is noted and, similarly, in patients with diminished
      hepatic function increased renal clearance seems to occur. Because of this
      compensatory elimination, fosinopril therapy for all patients can begin with the
      same recommended dosage. Fosinopril 10 to 40mg administered once daily is an
      effective antihypertensive regimen that has shown efficacy similar to that of
      enalapril 5 to 10 mg/day, propranolol 80 to 160 mg/day, hydrochlorothiazide 25 to
      50 mg/day and sustained release nifedipine 40 mg/day in preliminary clinical
      trials. Generally, fosinopril is well tolerated and adverse events associated
      with the drug are usually mild and similar to those associated with other ACE
      inhibitors. Thus, fosinopril appears to be a useful alternative to certain
      'established' agents used for treating patients with essential hypertension.

PMID- 1372858
TI  - Primary pulmonary hypertension. Practical therapeutic recommendations.
AB  - Primary pulmonary hypertension (PPH) is a rare disease of unknown aetiology which
      typically results in right heart failure and death within several years of the
      onset of symptoms. While there is no cure for PPH, several pharmacological and
      surgical approaches to treatment have been developed over the past decade which
      proved useful in a significant proportion of patients. In particular, vasodilator
      therapy may produce sustained haemodynamic and symptomatic improvement in up to
      approximately two-thirds of patients; in the remaining patients, vasodilators may
      either produce no benefit or result in deterioration. The calcium channel
      blocking agents are the most widely used oral vasodilators; continuous
      intravenous infusions of epoprostenol (prostacyclin; prostaglandin I2) have been
      used in some patients who are refractory to oral therapy, particularly as a
      bridge to transplantation. While combined heart-lung transplantation has been
      considered the surgical procedure of choice for severe pulmonary hypertension,
      single lung transplantation has been performed successfully in a small number of
      patients, and may be the preferred approach in patients with reasonably preserved
      right heart function.

PMID- 1372857
TI  - Vasodilators. A re-evaluation of their role in heart failure.
AB  - Over the past 25 years, the concept of circulation in heart failure has evolved
      from that of a simple circuit with a weak pump and high pressures to a complex
      integrated system of cellular modification, cardiac compensation and systemic
      neurohumoral responses. The original model of cardiac afterload as the systemic
      vascular resistance has been refined to reflect the interdependence of preload
      and afterload and the central role of atrioventricular valve regurgitation. It is
      becoming increasingly apparent that the impact of vasodilator therapy far exceeds
      the direct haemodynamic effects on preload and afterload, and depends on the
      mechanism by which vasodilation is achieved, with increasing emphasis on those
      agents which oppose neurohumoral activation. The potential goals of therapy have
      broadened to include not only haemodynamic stabilisation through tailored therapy
      for patients referred with advanced heart failure, but also the prevention of
      disease progression for patients with asymptomatic ventricular dilation. As the
      different profiles of heart failure have come to be recognised, the purpose and
      design of vasodilator treatment must now be considered individually for each
      patient.

PMID- 1372859
TI  - Pharmacological management of cancer pain.
AB  - Cancer pain remains a major cause of suffering. Improvements in its management
      have made unrelieved cancer pain unacceptable. While pharmacotherapy is the
      mainstay of cancer pain treatment, other options such as radiotherapy, nerve
      blocks, etc., have to be considered as well. A comprehensive approach must also
      address psychosocial issues. A successful pharmacotherapy programme for cancer
      pain requires careful assessment of the origin and cause of the pain. The
      selection of analgesics has to be rationalised using a sequential approach such
      as the WHO stepladder. Oral application by the block in an individually titrated
      dosage is recommended. Although morphine remains the most useful opioid, it
      should be used in combination with nonopioids. Co-analgesics, which contribute to
      analgesia without being classical analgesics, should be used to treat pain of
      specific origin. Here membrane-stabilizers, antidepressants and steroids play an
      often underestimated role in the treatment of neurogenic pain. Anxiolytics and
      major tranquillisers should be avoided because they cause sedation without
      improving quality of analgesia. Calcitonin, diphosphonates and spasmolytics are
      of minor importance in this regard. Finally, concomitant medication to treat side
      effects of the therapy may be necessary in formulating a comprehensive treatment
      plan.

PMID- 1372860
TI  - Practical treatment recommendations for the safe use of anaesthetics.
AB  - General anaesthesia is the reversible depression of central nervous system
      function. There is still no agreement over what constitutes depth of anaesthesia,
      and the clinical anaesthetist must thus titrate drug input according to clinical
      signs (heart rate, blood pressure, somatic movement, autonomic responses). The
      potency of inhalational agents may be expressed in terms of the MAC (minimum
      alveolar concentration); comparable end-points (including blood concentrations)
      have been proposed for the intravenous agents. Kinetic infusion regimens can be
      constructed for the intravenous agents to achieve the ED95 concentrations
      required to provide clinically adequate anaesthesia. However, because of
      individual differences in drug kinetics and dynamics, as well as the influences
      of disease states and intercurrent therapy, the clinician will titrate the dose
      according to response. Administration of volatile or intravenous anaesthetics by
      fixed regimens may result in either overdosage or the risk of patient awareness.
      The choice of anaesthetic drug is usually based on the nonhypnotic side effects
      of the different agents--including their central and regional cardiovascular
      effects, the speed and completeness of recovery, and the need to provide
      intraoperative analgesia. In addition, special techniques and drugs are often
      needed for neurosurgical, cardiothoracic and obstetric anaesthesia. All
      anaesthetic agents (inhalation and intravenous) have other side effects (such as
      cardiorespiratory depression and organ toxicity related to the liver or kidney).
      Both halothane and enflurane may be responsible for postoperative hepatic
      dysfunction, while the metabolism of enflurane can also result in nephrotoxicity
      in patients with pre-existing renal dysfunction. Isoflurane has been reported to
      cause 'coronary steal' in patients with ischaemic heart disease through its
      coronary vasodilator properties.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372861
TI  - Intravenous immune globulins. A review of their uses in selected immunodeficiency
      and autoimmune diseases.
AB  - Intravenous immune globulin (IGIV) was introduced a decade ago as a therapy for
      primary immunodeficiency diseases. It proved to be a valuable therapeutic
      substance for this purpose and is now considered to be the treatment of choice.
      The intent was to supply ubiquitous anti-infectious agent antibodies through
      passive immunisation to replace deficient circulating antibody content. During
      such therapy, unexpected benefits were noted in thrombocytopenic patients. Since
      that time, the therapeutic indications for IGIV infusions have greatly increased,
      with a particular interest in infectious, haematological and autoimmune diseases.
      This review summarises the status of IGIV therapy in haematological diseases
      within the categories of primary immunodeficiency diseases, secondary
      immunodeficiency states and autoimmune syndromes. The majority of firm data have
      been gathered on the treatment of patients with primary immunodeficiency disease.
      These data are reviewed from the aspect of anticipated therapeutic response and
      side effects. Emphasis should be placed on the IgG circulating blood levels as
      there is a need for individualizing therapy because of marked interindividual
      patient variation. The use of IGIV therapy in primary and secondary
      immunodeficiency states should consider the potential benefits to be attained in
      haematological malignancies and related complications which may be magnified by
      chemotherapy and radiation therapy. The mode of action of IGIV in autoimmune
      diseases, although not yet precisely determined, may involve establishing
      reticuloendothelial blockade or immunomodulation by supplying anti-idiotype
      antibodies.

PMID- 1372863
TI  - Molecular and biological properties of the vascular endothelial growth factor
      family of proteins.

PMID- 1372864
TI  - Reaction of adrenal glomerular zone to detergents.
AB  - The effects have been investigated of chronic exposure to detergents on
      volumetric and histochemical features of the glomerular zone of adrenal glands in
      the white rat. Neutral lipids, triglycerides, phospholipids and nucleic acids
      were analysed. There was an increase in the quantities of all the three fatty
      substances in the corticocytes of the glomerular zone and the quantity of
      ribonucleic acid was enhanced, whereas that of deoxyribonucleic acid was reduced.
      The volumes of the nuclei differed significantly between the experimental and the
      control animals.

PMID- 1372865
TI  - Characterization of a cis-acting regulatory element involved in human-aromatase P
      450 gene expression.
AB  - The characteristics of a cis-acting regulatory region involved in the human
      aromatase P-450 gene have been examined by transient expression analysis. The
      region spans from -242 - -166 relative to the cap site of the gene. A fragment
      containing the region excised from the gene enhances heterologous promoter
      activity as well as its own promoter activity in a position-independent and
      orientation-independent manner. The fragment exerts its enhancer activity in
      human BeWo choriocarcinoma cells in which the aromatase P-450 gene is expressed,
      but not in other cell lines tested. Deletion of 38 bp from the 3' end of the
      fragment results in a complete loss of enhancer activity. A gel-retardation assay
      with nuclear extracts from BeWo cells suggests the existence of a nuclear
      factor(s) which interacts with the fragment. These results suggest that the
      regulatory element in the fragment is involved in efficient transcription of the
      human-aromatase P-450 gene.

PMID- 1372866
TI  - The nucleotide and deduced amino acid structures of sheep and pig fetuin. Common
      structural features of the mammalian fetuin family.
AB  - This study was initiated to gain further insight into the structural features of
      the mammalian fetuin family. The cDNA structures of sheep and pig fetuin were
      determined. The cDNA insert encoding sheep (pig) fetuin comprised 1550 (1470)
      nucleotides, including 54 (46) nucleotides encoding a signal peptide of 18 (15)
      residues and 1038 (1041) nucleotides encoding the 346 (347) amino acids of the
      mature plasma protein. The predicted amino-terminal sequence of the mature pig
      fetuin was confirmed by the amino-terminal sequence of the purified protein.
      However, two alternative sheep amino-terminal sequences were found in fetuin
      purified from the plasma of a single sheep fetus; the minor product was the one
      predicted by comparison with other fetuin sequences while the major product was
      two amino acids longer. Comparison of the deduced amino acid sequences of sheep
      and pig fetuin showed an extensive sequence identity between them (75%) and with
      other proteins of the mammalian fetuin family, i.e. human alpha 2-HS
      glycoprotein, and bovine and rat fetuins. Twelve cysteine residues were found at
      invariant positions in all fetuin sequences, suggesting strongly that the
      arrangement of disulphide bridges identified in human alpha 2-HS glycoprotein is
      common to the members of the family. Further sequence comparisons revealed that
      the structures of mammalian fetuins are organised in three domains: two cystatin
      like domains (D1 and D2) and a complex carboxyl-terminal domain (D3). The
      proposed three-domain structure of the protein is reflected in the organisation
      of the rat fetuin structural gene which has recently been published.

PMID- 1372862
TI  - Amiodarone. An overview of its pharmacological properties, and review of its
      therapeutic use in cardiac arrhythmias.
AB  - Amiodarone, originally developed over 20 years ago, is a potent antiarrhythmic
      drug with the actions of all antiarrhythmic drug classes. It has been
      successfully used in the treatment of symptomatic and life-threatening
      ventricular arrhythmias and symptomatic supraventricular arrhythmias. In patients
      with left ventricular dysfunction amiodarone does not usually produce any
      clinically significant cardiodepression and the drug has relatively high
      antiarrhythmic efficacy. Preliminary studies indicate that amiodarone may have a
      beneficial effect on mortality and survival in certain groups of patients with
      ventricular arrhythmias, an action probably related to both its antiarrhythmic
      and antifibrillatory effects. The adverse effect profile of amiodarone is
      diverse, involving the cardiac, thyroid, pulmonary, hepatic, gastrointestinal,
      ocular, neurological and dermatological systems. Interstitial pneumonitis and
      hepatitis are potentially fatal, but the vast majority of adverse events are less
      serious, and some may be dose dependent. Pretreatment monitoring, regular
      assessments and the use of minimum effective doses are, therefore, necessary.
      Thus, with appropriate monitoring to control its well recognised adverse effects
      amiodarone has an important place as an effective 'broad spectrum' antiarrhythmic
      drug which has, so far, been used when other treatments have proved ineffective.
      More recent preliminary data also suggest that it may also have a beneficial
      effect in the prevention of sudden death in some patients.

PMID- 1372867
TI  - Diminished capacity to release metabolites of nitric oxide synthase in
      macrophages loaded with oxidized low-density lipoproteins.
AB  - Activation of J774-macrophages with lipopolysaccharide (LPS) or LPS and
      recombinant interferon-gamma (IFN-gamma) induced nitric oxide (NO) synthase
      activity, as measured by the production of nitrite and citrulline. NO synthase
      activity was suppressed by loading the cells with oxidatively modified low
      density lipoprotein (ox-LDL) but not with acetylated LDL (ac-LDL), although the
      intracellular lipid accumulation was comparable. This suggests that the extent of
      activation of lipid-loaded macrophages may be influenced by the type of lipid.

PMID- 1372868
TI  - Endopeptidase 24.15 modulates bradykinin-induced contraction in guinea-pig
      trachea.
AB  - Guinea-pig tracheal strips were contracted with cumulative concentrations of
      bradykinin or substance P in the presence of thiorphan, an inhibitor of
      endopeptidase 24.11 and of angiotensin-converting enzyme, or in the presence of N
      [1-(R,S)-carboxy-3-phenylpropyl]Ala-Ala-Phe-para-aminobenzoate (cFP-AAF-pAB), a
      selective inhibitor of endopeptidase 24.15. The concentration-effect curve of
      bradykinin was shifted to the left in the presence of each inhibitor whereas the
      curve of substance P was sensitive to thiorphan but not to cFP-AAF-pAB. These
      results show that endopeptidase 24.15 may modulate the contractile effect of
      bradykinin but not that of substance P in the guinea-pig trachea.

PMID- 1372869
TI  - Differential sensitivity of CG and CCG DNA sequences to ethionine-induced
      hypomethylation of the Nicotiana tabacum genome.
AB  - Plant DNA is distinguished from the DNA of all other organisms by its high
      content of 5-methylcytosine (5mC). 5mC levels may amount to 30% of total
      cytosines, distributed between the sequences CG and CXG. The results presented
      here show that the methylation status of CXG sequences could be influenced by
      culturing tobacco tissues on subtoxic concentrations of ethionine. The
      hypomethylating effect of ethionine, evaluated as the capability of MspI or HpaII
      to cleave the DNA, proved to be rather specific for CCG and differed from that of
      5-azacytidine which did not discriminate between CG and CXG sequences.

PMID- 1372870
TI  - Evaluation of endometrial tissue specific complement activation in women with
      endometriosis.
AB  - OBJECTIVE: To determine if endometrial tissue specific complement (C) activation
      occurs in patients with endometriosis. DESIGN: Prospective. SETTING: University
      of Oklahoma Health Sciences Center, a tertiary care referral center. PATIENTS:
      Twenty-six women, 9 with endometriosis and 17 without endometriosis.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Uterine and ectopic endometria were
      evaluated by the immunofluorescence assay for the presence of activated products
      of the initial (C3d) and terminal (C5b-9) C pathway, C3 regulatory proteins
      (decay-accelerating factor and membrane cofactor protein), and terminal C
      regulatory proteins (clusterin and vitronectin). RESULTS: The initial (C3d) and
      terminal (C5b-9) C components were deposited on blood vessel walls in uterine
      and/or ectopic endometria of women with and without endometriosis. In the stromal
      compartment at both sites, C deposition was colocalized with terminal C
      inhibitors/cell-cell attachment factors, clusterin and vitronectin on elastic
      fibers. No specific staining for C proteins was detected on the glandular
      epithelium of uterine and ectopic endometrial tissues examined. Furthermore,
      intense staining of endometrial epithelium for C3 regulatory proteins, decay
      accelerating factor, and membrane cofactor protein was noted on endometrial
      glands from women with and without endometriosis. CONCLUSIONS: Our findings
      demonstrate a lack of specific deposition of C in the glandular epithelial cells
      of endometria of women with endometriosis. The localization of C3 regulatory
      proteins, decay-accelerating factor, and membrane cofactor protein on glandular
      epithelium may suggest the involvement of intrinsic protective mechanisms on
      these cells from autologous C attack in vivo.

PMID- 1372871
TI  - Bibliography of developmental medicine and child neurology: selected books and
      articles received in 1991.

PMID- 1372872
TI  - Detection of Leptospiraceae by amplification of 16S ribosomal DNA.
AB  - The polymerase chain reaction (PCR) was developed to detect Leptospiraceae.
      Primers were used to amplify 1 631 base-pair (bp) 5'-region of 16S rDNA.
      Representative strains from the species, Leptospira interrogans sensu stricto, L.
      borgpetersenii, L. noguchii, L. santarosai, L. weilii, L. inadai, L. meyeri and
      the single member strain of Leptonema were amplified. In contrast, strains
      representing the saprophytic species. L. biflexa, L. wolbachii and L. parva were
      not amplified. There was no PCR product from 23 phylogenetically unrelated
      species of bacteria. As little as 10-1 pg of purified DNA and as few as 10-1
      leptospires could be detected using the PCR analysis. Isolates of leptospires
      from clinical sources gave a positive PCR band, but those from surface waters did
      not.

PMID- 1372873
TI  - Purification and characterization of LPS-free porins isolated from Salmonella
      minnesota.
AB  - Porins of Salmonella minnesota, R595, were purified by anion exchange
      chromatography and subsequently isolated in their monomeric form by
      chromatofocusing. Two forms of porin could be isolated, both with an apparent
      molecular mass of 37,000, but of differing isoelectric points (pI 4.6 versus pI
      of 4.9). Porins with pI 4.9 did not contain any detectable LPS, but porins with
      pI 4.6 were found to contain trace amounts of LPS (1.3 x 10(-4) micrograms LPS/1
      microgram porin) as measured using a highly sensitive limulus assay. Unlike the
      LPS-associated porins the monomeric porins were biologically inert with regard to
      pore formation, but they were still able to bind C1q, a subcomponent of the first
      component of complement.

PMID- 1372874
TI  - The serum resistance of gonococci in the majority of urethral exudates is due to
      sialylated lipopolysaccharide seen as a surface coat.
AB  - Examined before subculture, gonococci in 18 urethral exudates collected from
      different patients were serum-resistant. For 15 exudates, the resistance was
      drastically reduced by treatment with neuraminidase and by one subculture on
      laboratory media. It was restored by incubation with cytidine 5'-monophospho-N
      acetyl neuraminic acid (CMP-NANA). Electron microscopic examination of gonococci
      in eight exudates showed a surface structure stained by Ruthenium red which
      disappeared in most samples when they were treated with neuraminidase. These
      results were identical with those of previous studies on in vitro grown gonococci
      which had shown that serum resistance is due to sialylation of a 4.5-kDa
      conserved component of gonococcal lipopolysaccharide (LPS) by host CMP-NANA,
      which masks the target site for bactericidal IgM and renders surface LPS
      stainable by Ruthenium red. The serum resistance of gonococci in the remaining
      three exudates was not reduced by neuraminidase nor by subculture. The mechanism
      of this stable resistance is unknown.

PMID- 1372875
TI  - Percutaneous absorption of benzyl acetate through rat skin in vitro. 2. Effect of
      vehicle and occlusion.
AB  - The effect of vehicle and occlusion on the in vitro percutaneous absorption of
      [methylene-14C]-benzyl acetate (1.7-16.6 mg/cm2) has been studied in diffusion
      cells using full thickness skin from male Fischer 344 rats. Absorption of neat
      benzyl acetate through rat skin occluded with parafilm was 49.3 +/- 2.0% (mean +/
      SD, n = 4) after 48 hr. When benzyl acetate in ethanol was applied to the skin
      and the skin was occluded with parafilm, the extent of absorption at 48 hr was
      not significantly different from that after neat application. However at 6 hr, as
      the ethanol content of the application mixture was increased, the absorption of
      benzyl acetate through occluded skin was enhanced proportionally (r = 0.999).
      When phenylethanol was used as a vehicle, the extent of the benzyl acetate
      absorption through occluded skin at 48 hr was enhanced (P less than 0.05)
      compared with that after application neat; with 50% (v/v) phenyl-ethanol,
      absorption at 48 hr was 56.3 +/- 4.9%. However, this enhanced absorption did not
      correlate with the proportion of phenylethanol in the application mixture. When
      dimethylsulphoxide was used as a vehicle, the extent of absorption of benzyl
      acetate through occluded skin at 48 hr was enhanced (P less than 0.05) compared
      with that after application neat (absorption was 59.3 +/- 3.7% of the applied
      dose when 50% (v/v) dimethylsulphoxide was used). As the dimethylsulphoxide
      content of the application mixture was increased, the absorption of benzyl
      acetate was enhanced proportionally. Occlusion of the skin surface with parafilm
      often significantly enhanced absorption (P less than 0.05), although the effect
      varied with time and vehicle. In general, the degree of any enhanced absorption
      caused by the use of a vehicle or occlusion of the skin was small, and, in most
      cases, would be unlikely to be toxicologically significant.

PMID- 1372876
TI  - Is yohimbine-induced increase in salivary secretion a kinin-dependent mechanism?
AB  - We have previously reported that the alpha 2-adrenoceptor antagonist yohimbine
      induced a significant increase in both salivary flow rate and kallikrein output.
      In order to assess the possible role of the kinin-kallikrein system in the
      increase in salivary secretion elicited by yohimbine, the effects of aprotinin,
      an inhibitor of kallikrein activity, were investigated in yohimbine-treated
      conscious dogs. Aprotinin (at a dose, 5000 IU/kg iv, which reduced both resting
      and yohimbine-induced increase in kininogenase and amidolytic activities of
      saliva) which remained inactive alone, failed to modify the increase in salivary
      volume elicited by yohimbine (0.5 mg/kg iv). These results show that the rise in
      salivary flow rate observed under alpha 2-adrenoceptor antagonist is not induced
      by the kinin-kallikrein system. The release of kallikrein into saliva observed
      after yohimbine is rather the consequence than the cause of the increase in
      salivary secretion.

PMID- 1372877
TI  - Early detection of prostate cancer.
AB  - Prostate cancer is unique among the potentially lethal human malignancies in the
      wide discrepancy between the high prevalence of histologic changes recognizable
      as cancer and the much lower prevalence of the clinical disease. Despite the
      availability of effective tests for early detection and of effective treatment
      for cancers so detected, the diagnosis usually is not established until the tumor
      is locally advanced or metastatic. Yet, physicians hesitate to use these tests
      for fear that many cancers found would be latent, of little threat to the life or
      health of the host, and treatment could introduce inappropriate morbidity. Latent
      or "clinically unimportant" cancers can be distinguished from those that are
      clinically important by the larger volume, higher grade, and greater invasiveness
      of the latter. The available tests can detect only those cancers large enough to
      be palpable, visible on ultrasound, or capable of elevating the serum level of
      prostate-specific antigen. Such cancers are clinically important and should be
      treated for cure if the life expectancy of the patient is sufficiently long and
      the morbidity rate of therapy is low. Early detection of prostate cancer using
      the tests that are available today may widen the window of opportunity so that
      treatment indeed becomes possible in those for whom it is necessary.

PMID- 1372878
TI  - Prostatic intraepithelial neoplasia: a premalignant lesion.
AB  - Putative premalignant changes in the prostate have been recognized for a number
      of years. A variety of synonyms have been given to the most commonly described
      lesion, one characterized by proliferation and dysplasia of the normal two cell
      layers lining prostatic acini and ductules. Currently, "prostatic intraepithelial
      neoplasia" (PIN) is the term most commonly used to describe this entity. In this
      review, the requirements for a premalignant lesion, the reason why PIN fulfills
      the majority of these requirements, and a detailed description of the morphologic
      and phenotypic similarities between PIN and carcinoma will be outlined. Finally,
      the clinical significance of PIN will be reviewed.

PMID- 1372879
TI  - Histochemistry of the prostate.
AB  - Histochemistry, including immunohistochemistry, is helpful to the practicing
      pathologist in the diagnosis of prostatic carcinoma. Of equal importance,
      histochemistry is being increasingly used to study the pathobiology of the
      prostate. This article reviews these histochemical techniques and their
      applications.

PMID- 1372880
TI  - Elevated expression of ICAM1 (CD54) and minimal expression of LFA3 (CD58) in
      Epstein-Barr-virus-positive nasopharyngeal carcinoma cells.
AB  - Undifferentiated nasopharyngeal carcinoma (NPC) is a remarkable entity among
      human tumors because of its constant association with the Epstein-Barr virus
      (EBV). Malignant epithelial cells harbor the EBV genome and often express at
      least 2 species of latent EBV protein (EBNA1 and LMP1). Despite the massive
      presence of tumor-infiltrating lymphocytes, NPC cells obviously escape immune
      surveillance directed to EBV antigens. Previous investigations carried out on EBV
      positive Burkitt lymphoma (BL) cells have shown that this fact may be partially
      accounted for by a lack of expression of ICAM1 (CD54) and LFA3 (CD58). ICAM1 and
      LFA3 have therefore been investigated in fresh NPC biopsies and transplanted
      NPCs. With only 1 exception out of 9 cases, NPC cells appear to express high
      levels of ICAM1 and low levels of LFA3. This is a complete inversion of the
      pattern observed in normal epithelial cells in vivo. Additional investigations
      will be required to determine to what extent these characteristics affect T-cell
      interactions with NPC cells, specially in the process of EBV-antigen recognition.

PMID- 1372881
TI  - Recombinant interferon alpha-2A combined with prednisone in metastatic renal-cell
      carcinoma: treatment results, serum interferon levels and the development of
      antibodies.
AB  - Five partial responses were seen in 23 patients with metastatic renal-cell
      carcinoma (MRCC) receiving interferon-alpha 2a (IFN)+prednisone (P). Four of 24
      subsequent patients responded to IFN+P (combined response rate 19%). The median
      response duration was 8 months (3 to 30 months). The one-year survival for all
      eligible patients was 52%. Eight of 26 evaluable patients developed antibodies
      detected by an enzyme immunoassay. In 2 patients, high levels of neutralizing
      antibodies were also found, together with particularly low IFN levels. In one
      patient the development of neutralizing antibodies coincided with the loss of
      initial response. The treatment was well tolerated by most patients. Premature
      discontinuation of treatment was necessary in only 2 patients. In MRCC,
      combination treatment with IFN+P is as effective as IFN monotherapy (response
      rate 19%), with significantly reduced subjective toxicity. The clinical relevance
      of the development of antibodies against IFN requires further investigation.

PMID- 1372882
TI  - Tumorigenicity, mucin production and AM-3 epitope expression in clones selected
      from the HT-29 colon carcinoma cell line.
AB  - Two mucin-producing cell clones (16.2 and 12.2) and a mucin-deficient clone
      (15.2) were selected from the established human adenocarcinoma cell line HT-29 by
      limiting dilution and Alcian blue staining. The amounts of the mucin antigen
      detectable on the cell surface with the monoclonal antibody (MAb) AM-3 decreased
      in the order HT-29 greater than 16.2 greater than 12.2 greater than 15.2 = 0. The
      binding avidity of AM-3 antibody to cells as well as to mucin extracts from each
      cell line decreased in the same order, indicating that the epitope density on the
      cell-bound mucins was highest in HT-29 and lowest in 12.2 cells. The parental
      line and the mucin-producing cell clones 16.2 and 12.2 showed no contact
      inhibition and grew as aggregates, while the 15.2 cells were well spread and
      formed a regular monolayer. The mucin-producing cell lines injected into nude
      mice yielded solid tumors with different growth rates (HT-29 greater than 16.2
      greater than 12.2), while the 15.2 cell clone was not tumorigenic at all. The
      relative amounts of total mucin-bound hexoses and of the mucin epitope AM-3
      decreased in the xenografts in the order HT-29 greater than 16.2 greater than
      12.2. The present system is suitable for investigating the role of mucins in
      growth of colon carcinoma cells and indicates that increased tumorigenicity in
      nude mice coincides with the increase in total mucin expression and the
      expression of the AM-3 mucin epitope in tumor tissue.

PMID- 1372883
TI  - Patterns of angiogenic response to mast cell granule constituents.
AB  - Agents derived from mast cell granule constituents, and compound 48/80 which
      stimulates release of mast cell granules, have been used by us to develop new
      methods for quantitating angiogenesis in the chick chorioallantoic membrane. Two
      of these methods provide different insights, demonstrating different patterns of
      response to dosage and over time, produced by different agents. Counting
      mesenchymal blood vessels is convenient for obtaining dose-response data.
      Histamine and compound 48/80 have been shown previously to give a sigmoid dose
      response curve resulting in a plateau before the lethal dose. This contrasts with
      the effect of porcine sodium heparin (Evans Biologicals) which results in a minor
      increase then a relative decline in vessel number due to a failure of growth.
      Here, the ability to produce angiogenesis or antiangiogenesis appears to be dose
      dependent. Measurement of the changes in DNA synthesis, leading to visible
      angiogenesis, may be performed once the optimal angiogenic dose is known, and
      again distinctive patterns of response with different agents have been found.
      Histamine results in a fall then rise to a peak at 36 hr. We now show that two
      types of heparin each produce a peak at 12 hr. Compound 48/80 results in a
      distinctive pattern that looks like a composite of the histamine and especially
      the heparin effects, and this suggests that both are relevant to induction of
      angiogenesis by mast cells. The elicitation of this pattern of response also
      provides a method, additional to electron microscopy, for discovering whether or
      not an angiogenic substance is likely to operate via mast cell stimulation. Such
      characteristic patterns offer a new way of classifying angiogenic substances.

PMID- 1372884
TI  - Clinical experience with patient administered subcutaneous dihydroergotamine
      mesylate in refractory headaches.
AB  - This study examines the practicality and efficacy of dihydroergotamine mesylate
      (DHE) when self-administered subcutaneously in a population of refractory
      headache patients. Forty-three patients with chronic daily headache or migraine
      headache without aura, who had been taught self-injection of DHE either through
      the Raskin Protocol or in an outpatient headache clinic, were contacted by
      telephone and administered a questionnaire regarding usage and results from DHE
      injection. Ninety-two percent of patients could successfully administer DHE.
      Forty-six percent of patients experienced 90% or greater relief of pain and the
      majority of patients (77%) had greater than 50% relief. Emergency room use was
      decreased in 83% and 80% preferred DHE to their previous therapy. While side
      effects were common (79%), only four patients (9%) stopped DHE for this reason.
      No convincing evidence for the development of rebound headaches due to DHE was
      found in this sample.

PMID- 1372885
TI  - Production of multiple growth factors by a newly established human thyroid
      carcinoma cell line.
AB  - A multiple growth factor-producing tumor cell line (NIM-1) was newly established
      from a patient with thyroid cancer and remarkable neutrophilia. NIM-1 cells also
      caused severe neutrophilia in nude mice bearing tumors. NIM-1-conditioned medium
      (NIM-1CM) contained activities that supported not only granulocyte, macrophage
      and eosinophil colony formation of human bone marrow cells but also the growth of
      colony-stimulating factor (CSF)-dependent cell lines, NFS60-KX and TF-1. Northern
      blot hybridization analysis revealed the constitutive expression of granulocyte
      CSF (G-CSF), granulocyte/macrophage-CSF (GM-CSF) and interleukin(IL)-6 mRNAs in
      NIM-1 cells. Enzyme-linked immunosorbent assays (ELISA) using NIM-1CM also
      confirmed the production of IL-1 alpha and a small amount of IL-1 beta besides G
      CSF, GM-CSF and IL-6 in NIM-1 cells. In addition, unexpected production of IL-11
      in NIM-1 cells was detected by northern blot hybridization analysis and by
      bioassay using an IL-11-dependent cell line. Therefore, NIM-1 cell line is shown
      to produce multiple cytokines including potentially megakaryopoietic growth
      factors such as GM-CSF, IL-6 and IL-11.

PMID- 1372886
TI  - Site-dependent development of complete and incomplete intestinal metaplasia types
      in the human stomach.
AB  - The topographical distribution of complete and incomplete types of intestinal
      metaplasia in human stomach samples was investigated in order to elucidate their
      mutual histogenetic relationship and significance in carcinogenesis. Subgross
      stereomicroscopic examination of alcian blue and hematoxylin-stained gastric
      mucosae allowed clear distinction of complete and incomplete intestinal
      metaplasia types as white (with or without purple hue) and purple foci,
      respectively, against the background magenta areas of non-intestinalized mucosa.
      Intestinal metaplasias which developed in the fundic area were predominantly of
      the complete type whereas those of the antrum were a mixture of both with a
      distinct predilection for expression of the incomplete type. Although there was
      some variation among foci regarding the hue of white or purple, the color feature
      was principally homogeneous within each individual intestinal metaplasia focus.
      Thus phenotypic analysis indicated intestinal metaplasia expression to be clearly
      influenced by intragastric topography. The study did not provide any evidence
      that a shift from incomplete to complete type intestinal metaplasia may occur
      with time or that the incomplete type may be more intimately associated with
      development of well-differentiated carcinomas.

PMID- 1372887
TI  - Tumor-specific T cell lines: capacity to proliferate and produce interleukin 2 in
      response to various forms of tumor antigens.
AB  - Anti-tumor proliferative T cell lines were established from cultures of lymph
      node cells from BALB/c mice immunized to syngeneic CSA1M fibrosarcoma with the
      CSA1M tumor cell membrane. The cultures were maintained throughout in the absence
      of exogenous interleukin 2 (IL2). Cell surface phenotypes of all T cell lines
      established were Thy-1+, Ig-, L3T4+ and Lyt-2-. Their proliferation was induced
      in a tumor antigen dose-dependent fashion and a tumor antigen-specific way. Such
      proliferative responses were inhibited by the addition to cultures of anti-class
      II H-2d (anti-I-Ad) or anti-L3T4 but not of anti-class I H-2d or anti-Lyt-2
      monoclonal antibody. None of the T cell lines exhibited any cytotoxic T
      lymphocyte activity but they all produced IL2 upon stimulation with CSA1M tumor
      antigens, indicating that they represent helper-type T cell (Th) lines. The
      activation of these tumor-specific Th lines was induced with either CSA1M tumor
      cells themselves, or their membrane or detergent-solubilized fraction depending
      on the presence of antigen-presenting cells (APC). Most importantly, activation
      was also inducible by membranous tumor antigen-pulsed APC, which were capable of
      producing potent anti-tumor protective immunity when administered in vivo into
      syngeneic BALB/c mice. These results indicate that the tumor-specific Th lines
      established here can be activated with various forms of tumor antigens for their
      expression of helper function. Since Th lines of this type have not been
      described previously, our Th lines provide an intriguing tool for investigating
      the cellular and molecular mechanisms by which tumor-specific Th recognize tumor
      antigens.

PMID- 1372888
TI  - Sandwich capture ELISA by a murine monoclonal antibody against a genus-specific
      LPS epitope for the detection of different common serotypes of salmonellas.
AB  - A sandwich capture ELISA based on a murine monoclonal antibody against a genus
      specific epitope in the outer core region of the Salmonella lipopolysaccharide is
      described for the detection of different common serotypes of salmonellas. Four h
      broth cultures of seven standard and 24 wild strains of salmonellas were all
      detected by the capture ELISA while overnight broth cultures of 21 non-salmonella
      standard strains were all negative. The capture ELISA detected 1 ng/ml of Ra
      lipopolysaccharide, 10(6)/ml of a smooth wild strain of Salm. typhimurium, and
      1120 cells of Salm. heidelberg after enrichment culture for 4 h.

PMID- 1372889
TI  - Retrons and multicopy single-stranded DNA.

PMID- 1372890
TI  - The Tn10-encoded tetracycline resistance mRNA contains a translational silencer
      in the 5' nontranslated region.
AB  - We performed a mutational analysis of the left half of Tn10-encoded tet operator
      O2, located in the 5' nontranslated region of the mRNA for the resistance protein
      TetA, and determined the importance of that region for translation efficiency and
      mRNA stability. Transcriptional fusions of 17 mutants to lacZ expressed the same
      amounts of beta-galactosidase, while translational fusions varied 35-fold in
      expression efficiency. The mRNA half-lives varied 24-fold, with 9.6 min for the
      most highly expressed mRNA and 0.4 min for the least efficiently expressed mRNA.
      Toeprint experiments were performed to distinguish whether these mutations define
      a determinant of mRNA stability or influence translation initiation. The highly
      expressed mRNA was 24-fold more efficient in forming the initiation complex in
      vitro than the low-expression mutant. It was concluded that this sequence, albeit
      located upstream of the ribosome-binding sequence, is an important determinant
      for efficient initiation of translation. Secondary-structure calculations of the
      mRNAs revealed no correlation of the potential to form double strands masking the
      ribosome-binding sequence with expression efficiency.

PMID- 1372891
TI  - The cystic fibrosis transmembrane conductance regulator. Effects of the most
      common cystic fibrosis-causing mutation on the secondary structure and stability
      of a synthetic peptide.
AB  - Deletion of phenylalanine 508 (delta Phe-508) in the cystic fibrosis
      transmembrane conductance regulator (CFTR) protein causes approximately 70% of
      all cases of cystic fibrosis. This residue lies in a region of the protein that
      we have synthesized chemically and shown to bind adenine nucleotides (Thomas, P.
      J., Shenbagamurthi, P., Ysern, X., and Pedersen, P. L. (1991) Science 251, 555
      557). A peptide lacking this critical residue, but otherwise corresponding to
      this crucial part of the protein, now also has been chemically synthesized and
      purified. This mutant peptide (P-66) exhibits a significant loss of beta-sheet
      structure as compared with the wild type peptide (P-67). Furthermore, urea
      denaturation of peptide structure reveals that P-66 is less stable than P-67.
      Although under non-denaturing conditions both peptides bind adenine nucleotides
      with high affinity, the loss of structural stability is reflected in the binding
      function of the peptides. Thus, P-67, in contrast to P-66, retains a significant
      capacity for nucleotide binding in 4 M urea. These results suggest a model for
      impaired delta Phe-508 CFTR function.

PMID- 1372892
TI  - Characterization of the coexisting multiple mechanisms of methotrexate resistance
      in mouse 3T6 R50 fibroblasts.
AB  - We have studied the discrepancy in the degree of methotrexate (MTX) resistance
      that exists between two clonal cell lines, mouse 3T6 R50 cells and Chinese
      hamster ovary B11 0.5 cells that overexpress comparable levels of dihydrofolate
      reductase, yet exhibit a 100-fold difference in MTX resistance while maintaining
      similar sensitivity to the lipophilic antifolates trimetrexate and piritrexim.
      These data suggested that R50 cells may possess additional mechanism(s) of
      antifolate resistance, such as MTX transport alteration. Flow cytometric analysis
      using fluorescein methotrexate revealed comparable levels of fluorescein MTX
      displacement with lipophilic antifolates in viable R50 and B11 0.5 cells, but
      marked insensitivity of R50 cells to MTX competition, thus suggesting a poor
      uptake of MTX into R50 cells. Analysis of the kinetic parameters of dihydrofolate
      reductase from R50 cells neither showed alterations in enzyme affinities for
      various antifolates nor in the Michaelis constant for folic acid and NADPH nor a
      change in the pH activity optimum. R50 cell-free extracts contained wild-type
      levels of folylpoly-gamma-glutamyl synthetase activity. However, following
      metabolic labeling with [3H]MTX, no MTX polyglutamates could be detected in R50
      cells. We conclude that the high level of MTX resistance in R50 cells is
      multifactorial, including overexpression of dihydrofolate reductase, reduced MTX
      transport, and possibly altered formation of MTX polyglutamates. The potential
      interactions between the different modalities of MTX resistance in R50 cells are
      being discussed.

PMID- 1372893
TI  - Local anesthetics induce fast Ca2+ efflux through a nonenergized state of the
      sarcoplasmic reticulum Ca(2+)-ATPase.
AB  - The effect of the local anesthetics SKF 525-A, dibucaine, tetracaine, procaine,
      and benzocaine on sarcoplasmic reticulum vesicles was studied. All the
      anesthetics tested inhibited the phosphorylation of the Ca(2+)-ATPase by Pi in a
      competitive manner. Tertiary amine and positively charged anesthetics, in
      addition to competing with Pi, also decreased the apparent affinity of the ATPase
      for Mg2+. There was a good correlation between the octanol/water partition
      coefficients and the inhibitory activity of the different anesthetics. All the
      anesthetics tested induced a 5- to 10-fold increase in the rate of Ca2+ efflux.
      This was promoted by the same drug concentration that inhibited the
      phosphorylation of the ATPase by Pi. The effect on Ca2+ efflux was antagonized by
      the ligands of the ATPase (Mg2+, K+, Ca2+, MgATP, and ADP) and by the organic
      polyamines ruthenium red, spermine, spermidine, and putrescine. The natural anion
      heparin was found to potentiate the effect of the positively charged anesthetics
      on the rate of Ca2+ efflux. It is concluded that the local anesthetics increase
      the Ca2+ efflux through a nonenergized state of the Ca(2+)-ATPase, rather than
      promoting a nonspecific Ca2+ leakage through the membrane.

PMID- 1372894
TI  - Structure of an mdr-like gene from Arabidopsis thaliana. Evolutionary
      implications.
AB  - Multidrug resistance of mammalian tumor cells is caused by the enhanced
      expression of P-glycoproteins. These proteins are encoded by mdr genes and
      mediate the energy-dependent efflux of a variety of lipophilic drugs from cells.
      To test whether in plants mdr-like genes might be involved in certain cases of
      cross-resistance to different herbicides, we have cloned and characterized a gene
      from Arabidopsis thaliana, atpgp1, encoding a putative P-glycoprotein homologue.
      Like the mammalian P-glycoproteins, with which it shares extensive sequence
      homology and a similar organization in structural domains, this protein is
      internally duplicated. Seven of the nine introns in the atpgp1 gene match introns
      in the mammalian mdr genes to within a few nucleotides, and the positions of
      these suggest that P-glycoprotein genes evolved by duplication and subsequent
      fusion of an intron-containing primordial gene prior to the evolutionary
      separation of plants and mammals. The atpgp1 gene gives rise to transcripts
      present in all plant parts but particularly abundant in inflorescence axes.

PMID- 1372895
TI  - Identification of the fourth member of the mammalian endoprotease family
      homologous to the yeast Kex2 protease. Its testis-specific expression.
AB  - We used the polymerase chain reaction to identify a mouse testis cDNA that
      represented another member of a growing class of mammalian endoproteases involved
      in the processing of precursor proteins. This cDNA encoded a 655-residue protein,
      designated PC4, containing a bacterial subtilisin-like catalytic domain closely
      related to those of the recently characterized precursor-processing
      endoproteases, furin, PC1/PC3, PC2, and Kex2. Within this domain, the amino acid
      sequence of PC4 was 70, 58, 55, and 45% identical with those of mouse furin,
      mouse PC1/PC3, mouse PC2, and yeast Kex2, respectively. Northern blot analysis
      indicated that the PC4 mRNA was detectable only in the testes after the 20th day
      of postnatal development. Moreover, this message was mainly expressed in the
      round spermatids. These data suggest that PC4 represents a prime candidate for a
      precursor-processing endoprotease in the testicular germ cells and that its gene
      expression is regulated during spermatogenesis.

PMID- 1372896
TI  - Use of a multiple S1 nuclease protection assay to monitor changes in RNA levels
      for type 1 phosphatase and several proto-oncogenes in response to insulin.
AB  - Changes in insulin-regulated gene expression occur in a time- and tissue
      dependent fashion. To monitor these changes we have adapted the S1 nuclease
      protection assay to allow simultaneous estimation of multiple RNA species in a
      single sample by using synthetic oligonucleotides of various lengths as probes
      for specific RNA species, which can then be resolved by electrophoresis. The
      multiple S1 nuclease protection assay was used to assess the influence of insulin
      on the RNA concentrations of 12 different genes in human skeletal muscle.
      Estimates obtained by this assay were comparable with those obtained by Northern
      analysis. RNA levels for proto-oncogene c-src displayed a transient 4-fold
      increase, whereas RNA levels for type 1 protein phosphatase were suppressed by
      50% during the same time period. RNAs corresponding to known insulin-responsive
      genes such as c-fos, c-myc, c-Ha-ras, and c-src displayed rapid and transient 2-4
      fold increases between 30 and 60 min as detected by either Northern analysis or
      the multiple S1 nuclease protection assay. In addition, RNA levels for the
      insulin receptor, Glut-4, Glut-3, and c-jun were apparently unaffected by
      exposure of the cells to insulin.

PMID- 1372897
TI  - Fatty acid regulation of gene expression. Transcriptional and post
      transcriptional mechanisms.
AB  - Fatty acids are important metabolic substrates and may also be involved in
      pathological syndromes such as the insulin resistance of diabetes and obesity. We
      demonstrate here that fatty acids can regulate specific gene expression; mRNAs
      encoding the fatty acid binding protein adipocyte P2 (aP2) and the Fos-related
      transcription factor Fra1 are specifically induced at least 20-fold upon
      treatment of preadipocytes with oleate. For aP2, the effect requires long chain
      fatty acids and occurs without a generalized activation of the genes linked to
      adipocyte differentiation. Other fibroblastic cells without preadipocyte
      characteristics do not induce aP2 mRNA in response to fatty acids. Unlike aP2,
      Fra1 induction by fatty acids also can be detected in NIH 3T3 and 3T3-C2
      fibroblasts. Nuclear transcription assays in 3T3-F442A preadipocytes demonstrate
      that fatty acids elicit no transcriptional increase in the aP2 gene. Fra1, on the
      other hand, shows a 3-4-fold increase in transcription. These results demonstrate
      at least two distinct mechanisms by which fatty acids may influence gene
      expression.

PMID- 1372898
TI  - The Drosophila G protein gamma subunit gene (D-G gamma 1) produces three
      developmentally regulated transcripts and is predominantly expressed in the
      central nervous system.
AB  - A genomic clone, 536, located at the 44CD region of polytene chromosomes of
      Drosophila melanogaster, has been characterized for its neurobiological
      importance. We found that this clone contains a gene which produces 2.6-, 1.3-
      and 1.1-kilobase (kb) RNAs. While the 2.6-kb RNA is expressed only in the head,
      the 1.3-kb RNA is present exclusively in the body. The 1.1-kb RNA, however, is
      found in both the head and body, but in much higher concentration in the head.
      DNA sequence analysis of a 2.6-kb RNA-specific cDNA showed that this gene encodes
      a 70-amino acid polypeptide which is the putative Drosophila homologue to the
      gamma subunit of the bovine G-protein. The Drosophila protein, named D-G gamma 1,
      shares 46, 43, and 28% identity, and 59, 52, and 60% similarity, with the gamma
      2, gamma 3, and gamma t proteins of bovine G proteins, respectively. Sequencing
      of the 1.1-kb RNA-specific cDNA clone revealed that the 1.1-kb RNA is produced
      from the 2.6-kb transcription unit by usage of an alternative polyadenylation
      site, and has a coding region identical to that of the 2.6-kb RNA. Genomic
      Southern blot hybridization indicated that the Drosophila genome has only one D-G
      gamma 1 gene. Throughout development the 1.1-kb RNA is found to be the most
      prevalent species; its level peaks between 9 and 12 h of embryogenesis. As is the
      case for the other G protein genes of Drosophila, the D-G gamma 1 gene is
      predominantly expressed in the central nervous system of the fly.

PMID- 1372899
TI  - Structure and regulation of the glpFK operon encoding glycerol diffusion
      facilitator and glycerol kinase of Escherichia coli K-12.
AB  - The glpFK operon maps near minute 88 on the linkage map of Escherichia coli K-12
      with glpF promoter proximal. The glpF gene encodes a cytoplasmic membrane protein
      which facilitates the diffusion of glycerol into the cell. The glpK gene encodes
      glycerol kinase. In the present work, the nucleotide sequence of the 5'-end of
      the operon, including the control region, the glpF gene, and part of the glpK
      gene, was determined. The facilitator was predicted to contain 281 amino acids
      with a calculated molecular weight of 29,780. It is a highly hydrophobic protein
      with a minimum of six potential transmembrane alpha helices. The transcription
      start site for the glpFK operon was located 71 base pairs upstream from the
      proposed translation start codon for glpF. Preceding the transcription start site
      were sequences similar to the -10 and -35 consensus sequences for bacterial
      promoters. Binding sites for the cAMP-cAMP receptor protein (CRP) complex and the
      glp repressor were identified by DNase I footprinting. The region protected by
      the cAMP.CRP complex contained tandem sequences resembling the consensus sequence
      for CRP binding. The CRP sites were centered at 37.5 and 60.5 base pairs upstream
      of the start of transcription. The glp repressor protected an extensive area (-89
      to -7 relative to the start point of transcription), sufficient for the binding
      of four repressor tetramers. Two additional binding sites for the repressor were
      identified within the glpK coding region. The DNA containing these two operators
      synergistically increased the apparent affinity of glp repressor for DNA
      fragments containing the four operators in the promoter region of the glpFK
      operon. With this study, a total of 13 operators for the glp regulon have been
      characterized. Comparison of these operators revealed the consensus 5'-WATGTTCGWT
      3' for the operator half-site (W = A or T). The relative affinity of the glp
      repressor for the various glp operators was assessed in vivo using a promoter
      probe vector. The relative apparent affinity of the control regions for glp
      repressor was glpFK greater than glpD greater than glpACB greater than glpTQ. The
      degree of catabolite repression for each of the operons was assessed using a
      similar system. In this case, the relative sensitivity of the glp operons to
      catabolite repression was glpTQ greater than glpFK greater than glpACB greater
      than glpD.

PMID- 1372900
TI  - Mutations away from splice site recognition sequences might cis-modulate
      alternative splicing of goat alpha s1-casein transcripts. Structural organization
      of the relevant gene.
AB  - alpha s1-Casein variants F and D, synthesized in goat milk at lower levels than
      variant A, essentially differ from it by internal deletions of 37 and 11 amino
      acid residues, respectively. Northern blot analysis of mRNAs encoding alpha s1
      casein F and A and sequencing of the relevant cloned cDNAs, as well as sequencing
      of in vitro amplified genomic fragments, revealed multiple alternatively
      processed transcripts, from the F allele. Although correctly spliced messengers
      were identified, most of the FmRNAs lacked three exons. These exons, further
      identified as exons 9, 10, and 11, together encode the 37 amino acid residues
      present in alpha s1-casein variant A but missing in variant F. Exon 9 codes for
      the sequence present in variant A but deleted in variant D. A single nucleotide
      deletion in exon 9 and two insertions, 11 and 3 base pairs in length, in the
      downstream intron, were identified as mutations potentially responsible for the
      alternative skipping of these 3 exons. From a computer-predicted secondary
      structure it appeared that the 11-base pair insertion might be involved in base
      pairing interactions with the intron 5' splice site which might consequently be
      less accessible to U1 snRNA. We also report here the complete structural
      organization of the goat alpha s1-casein transcription unit, deduced from
      polymerase chain reaction experiments. It contains 19 exons scattered within a
      nucleotide stretch nearly 17-kilobase pairs long.

PMID- 1372901
TI  - Interleukin-1-inducible tumor growth arrest is characterized by activation of
      cell type-specific "early" gene expression programs.
AB  - Human melanoma cells, A375-C6, were "committed" to growth arrest within a few
      hours of exposure to interleukin-1 (IL-1). Co-treatment with actinomycin D
      rescued the cells from the "commitment," suggesting that "early" gene activation
      events may be crucial for growth arrest. To understand the mechanism of IL-1
      action, we are studying early genes whose expression is induced by the cytokine.
      Five early genes associated with IL-1 action in the melanoma cells were isolated
      by differential screening of a cDNA library, which was enriched for sequences
      representing IL-1 responsive genes (IRGs). Nucleotide sequencing identified four
      of the genes as gro-alpha, gro-beta, c-jun and nur77/NGF1-B/NAK1, respectively,
      while the fifth was judged as novel by GenBank search and designated IRG-9. None
      of the early genes was uniquely associated with the antiproliferative action of
      IL-1: other growth-inhibitory as well as growth-stimulatory signals induced these
      genes in diverse cell types. However, analysis of the induction patterns of the
      IRGs and other well known early genes revealed that IL-1 action in the melanoma
      cells is characterized by activation of a unique primary gene expression program.
      This program was defined by the magnitude and temporal pattern of induction of
      the five IRGs, feeble induction of c-fos, and lack of induction of Egr-1 and c
      myc. We present evidence that this program is growth arrest-specific in the
      melanoma cells and that distinct cell type-specific programs are associated with
      IL-1 growth-regulatory actions in other tumor cells. Based on these data, we
      propose that early genes may play multifunctional roles in tumor growth control,
      but specificity for the growth arrest action of IL-1 is determined by the
      composite early gene induction program.

PMID- 1372902
TI  - Primary structure and chromosomal localization of human and mouse rod
      photoreceptor cGMP-gated cation channel.
AB  - We have determined the primary structures of the human and mouse retinal rod cGMP
      gated cation channel by analysis of cDNA clones and amplified DNA. The open
      reading frames predicted polypeptides of 690 and 683 residues exhibiting 88%
      sequence similarity. Sequence comparison indicated that the rod channels consist
      of a variable 90-residue N-terminal region, a short highly charged segment rich
      in lysine and glutamate, and a 540-residue C-terminal portion that is well
      conserved in three mammalian species. Significant sequence similarity (59%) of
      the visual cGMP-gated channel to the olfactory cAMP-gated channel established the
      existence of a family of cyclic nucleotide-gated ion channel genes. RNA blot
      analysis revealed transcripts of 3.2 kilobases (kb) in human, mouse, and dog,
      3.2, 4.6, and 5.2 kb in bovine, and 3.6 kb in fish. The human channel gene was
      mapped by polymerase chain reaction of somatic cell hybrid DNAs to chromosome 4
      (p14-q13) near the centromere. The mouse channel gene locus (Cncg) was mapped by
      interspecific backcross haplotype analysis 0.9 centimorgan proximal of the Kit
      locus on chromosome 5.

PMID- 1372903
TI  - Epitope mapping of anti-recA protein IgGs by region specified polymerase chain
      reaction mutagenesis.
AB  - Monoclonal IgGs were shown to be useful for the specific inhibition of a set of
      activities of the recA protein, a key protein in homologous genetic
      recombination. The mapping of the epitopes for these IgGs and site-directed
      mutagenesis based on the mapping will facilitate location of the functionally
      active sites on the tertiary structure of the protein, which is being solved by
      means of physicochemical techniques. We developed a novel technique for region
      specified mutagenesis and applied the technique to epitope mapping. Using the
      polymerase chain reaction in the presence of deoxyinosine triphosphate, we
      introduced random base substitutions specifically into a region of the recA gene
      defined by a pair of primers. RecA mutants exhibiting altered antigenicity were
      selected, in plaque-immunoblotting experiments, from libraries of mutagenized
      recA genes constructed on the lambda gt11 expression vector. Mutant recA genes
      were obtained at the frequency of about 10(-2) among the plaques expressing fused
      recA genes and then each one was expressed as a whole protein, which was
      characterized by enzyme-linked immunosorbent assay. Analyzing the DNA sequences
      of the mutant recA genes, we located at the amino acid sequence level the
      epitopes for two anti-recA IgGs which could not be located in previous studies.
      One of the antibodies was shown to prevent self-assembly of the recA protein and
      the other was suggested to inhibit the binding of double-stranded DNA. Thus, the
      active sites involved in these functions would be located in the space around or
      near the relevant epitope.

PMID- 1372904
TI  - Cloning of the cDNa for a Na+/myo-inositol cotransporter, a hypertonicity stress
      protein.
AB  - Kidney medullary cells in situ, as well as kidney-derived Madin-Darby canine
      kidney (MDCK) cells accumulate nonperturbing, small organic solutes (osmolytes),
      including myo-inositol, when bathed in hypertonic media. Accumulation of
      osmolytes balances the osmolality of extracellular fluid without raising
      intracellular salts that would perturb cellular functions. In hypertonic media,
      increased myo-inositol accumulation is the result of increased activity of a
      Na+/myo-inositol cotransporter. We have isolated a cDNA encoding a Na+/myo
      inositol cotransporter from MDCK cells using expression in Xenopus oocytes. The
      cDNA sequence predicts a protein of 718 amino acids with a significant amino acid
      sequence similarity to the Na+/D-glucose cotransporters of absorbing epithelia.
      Transporter mRNA is present in kidney and brain and is markedly induced in MDCK
      cells by medium hypertonicity, demonstrating that adaptation to hypertonic stress
      involves up-regulation of transporter mRNA accumulation.

PMID- 1372905
TI  - Design and immunological properties of topographic immunogenic determinants of a
      protein antigen (LDH-C4) as vaccines.
AB  - Antibodies elicited by immunization with short peptides containing antigenic
      determinants have been shown, in general, to bind with greatly reduced affinity
      to the corresponding region in the native proteins. Thus, contiguous linear
      peptides have not proven to be effective immunogens in generating high affinity
      neutralizing or protective antibodies and consequently appear to be poor
      prospects for vaccines. The molecular basis for such reduced reactivity is clear
      from the crystal structure determination of antibody Fabs bound to protein
      antigens, which showed the complementarity between interfaces to be lock-and-key
      like and extending over a large area (750 A2) involving discontinuous segments of
      the polypeptide chain. Thus, small perturbations in the secondary and tertiary
      structure of the antigen have profound effects on the fit of the antigen and its
      corresponding antibody. Because short peptides are unlikely to assume any
      particular conformation in solution, the fit is likely to be poor. New strategies
      are therefore required to produce conformationally stable peptides that mimic the
      critical structural features of the protein antigenic site. Here we show that a
      putative topographic determinant of the testis-specific isozyme of lactate
      dehydrogenase C4 (LDH-C4), designed and synthesized to adopt a well defined alpha
      helical secondary and tertiary structure (four-helix bundle motif) in aqueous
      solutions, is highly immunogenic in both rabbits and mice, inducing IgG
      antibodies that bind to native LDH-C4. This engineered conformational 40-residue
      peptide is considerably more effective in inducing antibodies, as compared with
      the corresponding linear peptide. The antibody response is obtained without
      coupling the peptide to a carrier protein, suggesting that the peptide contains a
      T-cell antigenic determinant. The strategy described here to produce a
      conformationally stable peptide that mimics the native structure may have general
      applications in vaccine design.

PMID- 1372906
TI  - Identification of alpha 2-macroglobulin conformational intermediates by electron
      microscopy and image analysis. Comparison of alpha 2-macroglobulin-thrombin and
      alpha 2-macroglobulin reacted with cis-dichlorodiammineplatinum(II) and trypsin.
AB  - Human alpha 2-macroglobulin (alpha 2M) exists in two well defined, highly
      distinct conformations and in less well described intermediate conformations. In
      this study, previously characterized reactions were used to partially or
      completely transform the conformation of alpha 2M. Electron micrographs of each
      preparation were subjected to image analysis. Ternary alpha 2M-trypsin (2 mol of
      trypsin/mol of alpha 2M) was analyzed as a control for the fully transformed
      state. Correspondence analysis (CORAN) and hierarchical ascendant classification
      (HAC) generated five image clusters from 330 aligned alpha 2M-trypsin complexes.
      Average images of each cluster resembled the letter "H" with four nearly
      equivalent lateral arms. Abnormally shaped lateral arms were not demonstrated by
      HAC, using a variety of factor sets. In a native polyacrylamide gel
      electrophoresis system, alpha 2M-thrombin migrated in a diffuse band partially
      behind alpha 2M-trypsin, suggesting conformational heterogeneity. CORAN and HAC
      of 733 alpha 2M-thrombin complexes identified two neighboring clusters, the
      average images of which showed an H-like structure in which one arm was replaced
      by a globular stain-excluding body. The two alpha 2M-thrombin clusters included
      125 images (17.1% of image population). The complete absence of atypical lateral
      arm structure in the alpha 2M-trypsin clusters suggests that this variation is
      not the result of orientation or staining artifact. Native alpha 2M was reacted
      with cis-dichlorodiammineplatinum(II) and then with trypsin to form alpha 2M-Pt
      trypsin, a preparation that includes partially transformed alpha 2M structures.
      CORAN and HAC of 580 alpha 2M-Pt-trypsin complexes generated five clusters, the
      average images of which showed atypical lateral arm structure equivalent to that
      demonstrated with alpha 2M-thrombin. The five alpha 2M-Pt-trypsin clusters
      accounted for 15.2% of the image population. These studies suggest that alpha 2M
      conformational change intermediates demonstrate common structural
      characteristics, permitting an elucidation of the steps involved in this complex
      transformation.

PMID- 1372907
TI  - Molecular cloning and functional expression of an inducible nitric oxide synthase
      from a murine macrophage cell line.
AB  - Macrophages activated by exposure to cytokines and/or to endotoxin produce nitric
      oxide (NO.), a free radical that is a mediator of the host response to infection.
      Activation induces the expression of nitric oxide synthase, the enzyme that
      catalyzes formation of NO. from L-arginine and molecular oxygen. We report the
      cloning of a cDNA encoding the inducible nitric oxide synthase from a murine
      macrophage cell line, RAW264.7, exposed to interferon-gamma and
      lipopolysaccharide. Oocytes injected with mRNA transcribed from this cDNA
      demonstrate arginine-dependent production of nitrite, a stable metabolite of NO..
      Nitric production is blocked by the enzyme inhibitor, NG-monomethylarginine, and
      is independent of calcium/calmodulin. RAW264.7 cells demonstrate rapid
      accumulation of the nitric oxide synthase-encoding mRNAs upon activation.
      Comparison of the deduced amino acid sequence to the calcium/calmodulin-dependent
      nitric oxide synthase previously purified (Bredt, D. S., and Synder, S.H. (1990)
      Proc. Natl. Acad. Sci. U. S. A. 87, 682-685) and cloned (Bredt, D. S., Hwang, P.
      M., Glatt, C. E., Lowenstein, C., Reed, R. R., and Synder, S. H. (1991) nature
      351, 714-718) from rat brain identifies shared binding sites for the cofactors
      NADPH and flavins in the C-terminal half of both proteins and an additional
      conserved region near the N terminus that may recognize L-arginine and/or
      contribute to the active site.

PMID- 1372908
TI  - Cofactor residues lysine 165 and 166 are critical for protein substrate
      recognition by the tissue factor-factor VIIa protease complex.
AB  - High affinity binding of factor VIIa (VIIa) to its cellular receptor tissue
      factor (TF), as well as association of factor X with phospholipid are required
      for optimal assembly of the extrinsic activation complex. In addition to the
      interactions of substrate with phospholipid and enzyme, we here provide evidence
      that cofactor residues Lys-165 and Lys-166 specifically contribute to the
      recognition of macromolecular substrate. Ala for Lys replacement in TFA165A166
      was compatible with high affinity binding of VIIa when analyzed on cell surfaces
      as well as in the absence of phospholipid. Dissociation of TFA165A166.VIIa did
      not occur with a faster rate compared to TF.VIIa, further supporting unaltered
      VIIa binding function of TFA165A166. Cleavage of chromogenic peptidyl substrate
      by TFA165A166.VIIa complexes was not diminished, demonstrating that TFA165A166
      supported enhancement of catalytic function of the VIIa protease domain. In
      contrast, factor X activation was reduced in the presence and absence of
      phospholipid. Further, TFA165A166 effectively competed with wild-type TF in the
      cleavage of factor X at limited VIIa concentrations. Selective reduction in
      macromolecular substrate hydrolysis combined with normal VIIa binding by
      TFA165A166 indicates that the cofactor TF does contribute, either directly or
      indirectly via specific interactions with VIIa, to factor X recognition.

PMID- 1372909
TI  - Role of integrin alpha 4 beta 7/alpha 4 beta P in lymphocyte adherence to
      fibronectin and VCAM-1 and in homotypic cell clustering.
AB  - Integrins are heterodimeric cell surface proteins that mediate both cell-cell and
      cell-extracellular matrix interactions. We and others recently identified cDNAs
      encoding a novel integrin beta subunit, beta 7, in lymphocytes. We have now
      detected beta 7 mRNA in mouse TK-1 T lymphoma cells, which are known to express
      the putative Peyer's patch homing receptor alpha 4 beta P. We used an anti
      peptide antiserum and a novel mAb against the beta 7 subunit to show that TK-1
      cells express beta 7 as the only subunit associated with alpha 4. We conclude
      that beta 7 and beta P are identical. We also show that activated peripheral
      blood T cells express alpha 4 beta 7. We studied the function of alpha 4 beta
      7/alpha 4 beta P in TK-1 cells, which do not express very late antigen (VLA)-4
      (alpha 4 beta 1). Cells adhered to intact fibronectin and to a fibronectin
      fragment containing the CS-1 region, but not to a fragment containing the RGD
      sequence. Adhesion to fibronectin was inhibited by antibodies to alpha 4,
      suggesting that alpha 4 beta 7 is a fibronectin receptor. We confirmed that alpha
      4 beta 7 binds to the CS-1 region of fibronectin using affinity chromatography.
      TK-1 cell adhesion to the vascular cell adhesion molecule VCAM-1 was also
      inhibited by antibodies to alpha 4, implying that alpha 4 beta 7 also plays a
      role in the adherence of lymphocytes to endothelial cells. TK-1 cell binding to
      fibronectin and VCAM-1 is markedly increased by brief PMA stimulation. We also
      found that mAbs against alpha 4 and beta 7 induce homotypic clustering of TK-1
      cells. Taken together these results suggest that alpha 4 beta 7/alpha 4 beta P
      recognizes some or all of the same widely distributed ligands recognized by VLA-4
      (alpha 4 beta 1) and that the role of alpha 4 beta 7/alpha 4 beta P may not be
      restricted to lymphocyte homing.

PMID- 1372910
TI  - Characterisation of visna virus reverse transcriptase: a micro scale reverse
      transcriptase assay adapted for use with an automated cell harvester.
AB  - The reverse transcriptase of the sheep lentivirus visna/maedi virus has been
      characterised. Optima for magnesium ion concentration (5-10 mM), potassium ion
      concentration (150 mM) and pH (8.25) for this enzyme are very similar to those
      previously described for the human immunodeficiency viruses. The assay used for
      this work makes use of a cell harvester to speed up the processing of multiple
      samples. It is small scale, requiring 15 microliters of sample, is rapid, and is
      able to detect virus at titres below 10(3)/ml. Harvesting the assay onto either
      DEAE paper or using TCA and glass fibre mats make it suitable for use with either
      tissue culture media or infected cell lysates, but not with body fluids. It has
      been used to detect cell-associated reverse transcriptase in choroid plexus cells
      within 36 h of visna infection.

PMID- 1372911
TI  - Detection of HIV-1 RNA in heparinized plasma of HIV-1 seropositive individuals.
AB  - The interference of reverse transcription by heparin was removed by heparinase.
      When the HIV-1 RNA in the presence of heparin was detected by a combination of
      reverse transcription and the polymerase chain reaction (PCR), heparinase
      treatment followed by removal of Ca2+ before the reverse transcription step
      permitted the efficient detection of HIV-1 RNA. Prior treatment with heparinase
      revealed HIV-1 RNA in 68% (13/19) of heparinized plasma samples from HIV-1
      carriers, whereas only 26% (5/19) of the same specimens were positive without the
      heparinase step. Heparinase removed the inhibition of reverse transcription by
      heparin and is highly recommended when detecting low levels of viral RNA in
      heparinized plasma.

PMID- 1372912
TI  - Immunoelectron microscopic epitope locations of titin in rabbit heart muscle.
AB  - The location of cardiac titin epitopes in the sarcomere of rabbit cardiac, atrial
      and ventricular muscle was studied by using polyclonal antibodies against
      skeletal muscle titin. The results show that incubation with the antibody leads
      to the appearance of four electron-dense stripes in the A band of both atrial and
      ventricular cardiac muscle. The location and intensity of these stripes were
      identical to those observed in skeletal muscle. In conclusion we demonstrate that
      titins from skeletal and cardiac muscles share some common antigenic
      determinants.

PMID- 1372913
TI  - Protein C inhibitor in human body fluids. Seminal plasma is rich in inhibitor
      antigen deriving from cells throughout the male reproductive system.
AB  - An assay was developed for the measurement of human protein C inhibitor antigen
      (PCI) in blood plasma and other biological fluids. Both native PCI, modified
      inhibitor, and complexes of inhibitor with activated protein C or plasma
      kallikrein could be measured with the assay. Inhibitor antigen concentrations
      were found to be very high in seminal plasma (greater than 200 mg/liter), more
      than 40 times the concentration of PCI found in blood plasma. The inhibitor in
      seminal plasma was unable to form complexes with activated protein C. Gel
      filtration and immunoblotting findings indicated that the inhibitor in seminal
      plasma is present in a high molecular mass complex or cleaved to its modified
      form. As PCI antigen was absent from seminal plasma of patients with
      dysfunctional seminal vesicles, the seminal vesicle glands would appear to be the
      major source of seminal plasma PCI, a conclusion supported by immunohistochemical
      demonstration of the presence of PCI epitopes in the secretory epithelium of the
      seminal vesicles. Specific PCI immunoreactivity was also shown to be present in
      the testes, the epididymis glands, and the prostate, suggesting the inhibitor to
      have a complex or multiple function in the male reproductive system. Conclusive
      evidence of a local synthesis of PCI in the four male sex glands was provided by
      Northern blot analysis of RNA from these organs.

PMID- 1372914
TI  - Decreased serum insulin-like growth factor-I associated with growth failure in
      newborn lambs with experimental cyanotic heart disease.
AB  - To determine whether chronic hypoxemia results in alterations in endocrine
      function that may contribute to growth failure, we measured growth hormone (GH),
      somatomedins (insulin-like growth factors I and II, IGF-I and IGF-2), hepatic
      growth hormone receptors, and circulating IGF-binding proteins IGFBP-3 and IGFBP
      2 in 12 newborn lambs with surgically created pulmonic stenosis and atrial septal
      defect, and in 10 controls. During chronic hypoxemia (oxygen saturation of 60-74%
      for 2 wk), weight gain was 60% of control (hypoxemic, 135 +/- 20 vs. control, 216
      +/- 26 g/d, P less than 0.02). IGF-I was decreased by 43% (hypoxemic 253.6 +/-
      29.3 SE vs. control 448.0 +/- 75.5 ng/ml, P = 0.01), whereas GH was unchanged
      (19.9 +/- 5.1 vs. 11.9 +/- 3.0 ng/ml, NS). The increase in IGF-1 was associated
      with a decrease in IGFBP-3 (hypoxemic, 5.09 +/- 1.25 vs. control, 11.2 +/- 1.08
      arbitrary absorbency units per mm (Au.mm), P less than 0.01), and increase in
      IGFBP-2 (0.47 +/- 0.03 vs. 0.19 +/- 0.13 Au.mm, P less than 0.05), but no
      significant downregulation of hepatic GH receptors (hypoxemic, 106.1 +/- 20.1 vs.
      control, 147.3 +/- 25.9 fmol/mg, NS). Thus, chronic hypoxemia in the newborn is
      associated with a decrease in IGF-I and IGFBP-3 in the face of normal GH. This
      suggests peripheral GH unresponsiveness, similar to protein-calorie malnutrition
      or GH receptor deficiency dwarfism, but mediated at a level distal to the hepatic
      GH receptor.

PMID- 1372915
TI  - The breadth of developmental and behavioral services.

PMID- 1372916
TI  - Configuration of immunoglobulin and T cell receptor beta and gamma genes in acute
      myeloid leukaemia: pitfalls in the analysis of 40 cases.
AB  - AIMS: To evaluate the overall incidence of immunoglobulin (Ig) and T cell
      receptor (TCR) beta and gamma gene rearrangements in a series of 40 cases of
      acute myeloid leukaemia (AML) and to determine whether structural modifications
      of these genes could be correlated with the abnormal expression of lymphoid
      markers in malignant cells. METHODS: All cases were classified according to the
      criteria of the FAB group and immunophenotyped with a panel of monoclonal
      antibodies reactive with myeloid and lymphoid differentiation antigens. DNA
      analysis was performed by the method of Southern using probes for the Ig JH, TCR
      C beta 1, and TCR-J tau 1 regions. RESULTS: Phenotypic analysis showed that in
      addition to myeloid markers, 10 cases expressed lymphoid antigens: CD7 in seven
      (of which three were TdT positive, one CD2 positive, and one CD19 positive) and
      CD19 in three. Southern blot analysis showed that bands with sizes different from
      the germ line control were present in the TCR beta genes in 11 cases: in six of
      30 with pure myeloid phenotype and in five of 10 of those expressing lymphoid
      markers. A close observation of the size and patterns of those bands, however,
      showed that they could be artefactual. Indeed, further analysis showed that they
      were either due to resistant Eco RI/Hind III sites at the beta locus or to
      plasmid contamination. Rearranged genes were eventually found in only two of the
      40 cases: at the Ig JH region in one of the 30 with pure myeloid phenotype (3.3%)
      and at the TCR gamma genes in one of 10 with lymphoid markers (10%). CONCLUSIONS:
      These observations showed that Ig/TCR gene rearrangements were rare in this AML
      series (overall incidence of 5%) and that they were not significantly more common
      in cases with aberrant expression of lymphoid markers. The size and pattern of
      the potential non-germline bands that can be found in these loci must be
      carefully evaluated.

PMID- 1372917
TI  - Two-colour immunoenzymatic technique using sequential staining by APAAP to
      evaluate two cell antigens.
AB  - AIMS: To extend the alkaline phosphatase-antialkaline phosphatase (APAAP)
      immunoenzyme single stain method to a more generally applicable double stain
      technique. This will allow two primary antibodies of the same isotype of IgG and
      specifically the nuclear antigen bromodeoxyuridine (BRdU) to be evaluated with a
      cell surface antigen identifier. METHOD: Sequential applications of the APAAP
      method showed two antigen sites by different dye couplings to a common alkaline
      phosphatase substrate, producing blue and red reaction products on the same
      slide. Antigens on different cell populations as well as those in different
      compartments of the same cell were analysed. The method allowed a surface antigen
      monoclonal to be revealed first, using an optimal fixative, before
      alcohol/gluteraldehyde fixation was used to start the second (BRdU) staining
      sequence. RESULTS: An analysis of double staining of T lymphocyte subsets (CD4
      and CD8) showed no significant difference in the order of application of the
      primaries (n = 10) and no significant difference from their corresponding single
      stain results (n = 50), confirming the validity of the technique where antigens
      are exclusively distributed. Other examples, including antigens distributed in
      different compartments of the same cell, displayed discrete staining which
      implied validity. CONCLUSION: Double staining by APAAP with this technique seems
      to be applicable to those cases where antigens are exclusively distributed and
      includes cases where different compartments of the same cell are stained. It is
      especially useful in revealing antigens that require different fixation and
      preparation--that is DNA incorporated BRdU with a surface antigen. But it does
      seem to have a limited ability to produce a dual colour at a common site.

PMID- 1372918
TI  - New screening system for simultaneous determination of two marker proteins by
      homogeneous enzyme immunoassay.
AB  - AIMS: To save time and labour in mass screening, by detecting two marker proteins
      on one specimen using only one test. METHODS: alpha Fetoprotein and ferritin were
      chosen to demonstrate the principal of this system. The assay reagents were
      horseradish peroxidase (HRP)-labelled anti-alpha fetoprotein and HRP-labelled
      anti-ferritin antibodies. After the serum sample had been incubated with these
      reagents the substrate for HRP was added and the absorbance measured. An
      absorbance value below the cutoff point indicated that both parameters were
      within normal limits; a value above the cutoff point indicated that at least one
      of the two parameters was abnormally high. RESULTS: Fifty sera from healthy
      Japanese subjects were assayed by the simultaneous assay method. All samples gave
      absorbancy values below the cutoff point. Fifty serum samples from patients with
      high alpha fetoprotein concentrations (over 20 ng/ml) and 50 samples with high
      ferritin concentrations (over 200 ng/ml) were also assayed. The absorbancy values
      of all samples with high alpha fetoprotein concentrations, and all but one sample
      with high ferritin concentrations gave values above the cutoff point.
      CONCLUSIONS: Although this homogeneous enzyme assay method was applied to the
      combination of alpha fetoprotein and ferritin, it could be used in mass screening
      for any other combination of two markers.

PMID- 1372919
TI  - Hepatocholangioadenoma in a pig.
AB  - A Landrace sow had several neoplastic nodules in the liver. Histopathologically,
      the individual nodules consisted of two types of closely associated neoplastic
      cells; one was of hepatocellular type, the other of cholangiocellular type. Based
      on this finding, the term "hepatocholangioadenoma" is considered to be
      appropriate for this tumour. Previously reported in man, the dog and the duck, a
      mixed type of primary hepatic neoplasm has now been found in the pig.

PMID- 1372920
TI  - Poorly differentiated squamous cell carcinomas of the skin can express vimentin.
AB  - Thirty cases of poorly differentiated carcinomas of the skin were examined for
      the expression of vimentin. All cases expressed cytokeratins; in addition, 12
      cases were positive for vimentin. These were all non-reactive with antibodies to
      S100 protein, HMB45 and desmin. The finding of vimentin in poorly differentiated
      squamous cell carcinomas underscores the need for caution in the use of
      immunohistochemical stains for tumor typing. Cutaneous squamous cell carcinomas
      are an addition to the list of epithelial tumors which are known to coexpress
      vimentin intermediate filaments. Other carcinomas which consistently express
      vimentin include those of renal, endometrial, thyroid, pulmonary, ovarian,
      salivary gland, adrenal and more recently, those of breast and prostatic origin.

PMID- 1372921
TI  - Neutrophil elastase and its inhibitors in human gingival crevicular fluid during
      experimental gingivitis.
AB  - The relative concentrations and absolute amounts of neutrophil elastase and its
      two inhibitors, alpha 2-macroglobulin (alpha 2-M) and alpha 1-antitrypsin (alpha
      1-AT), were determined in gingival crevicular fluid (GCF) collected from six
      dental students who refrained from brushing the upper left or right quadrant
      during three weeks. Plaque and gingival indices and flow of GCF were measured
      before, during, and after the three weeks of no brushing. Functional elastase,
      representing the enzyme complexed with alpha 2-M, was measured by use of a low
      molecular-weight fluorogenic substrate. Elastolytic activity in GCF was also
      assayed by use of elastin as substrate. Antigenic elastase, representing the
      enzyme complexed with alpha 1-AT, as well as the inhibitors alpha 2-M and alpha 1
      AT were measured by ELISA. After three weeks of plaque accumulation, the
      concentrations of both functional and antigenic elastase increased by a factor of
      about 3, whereas the concentrations of the inhibitors increased in a much higher
      proportion. No free elastase could be detected in GCF, as evidenced by the
      Sephadex G-75 elution profile of GCF, by the negative results obtained when
      elastin was used as substrate, and by the demonstration that pure enzyme kept its
      activity against the low-molecular-weight substrate after being saturated by
      alpha 2-M.

PMID- 1372922
TI  - Postprandial cholecystokinin secretion in elderly with protein-energy
      undernutrition.
AB  - OBJECTIVE: Malnutrition is currently observed in aged people, and cholecystokinin
      is an important peripheral satiety signal. The aim of this study was to examine
      the effect of aging and protein-energy malnutrition on postprandial
      cholecystokinin (CCK) release. DESIGN: Non-randomized, cross-sectional comparison
      by age group. SETTING: Gastroenterology section of a teaching hospital.
      PARTICIPANTS: Twenty-one human volunteers divided into three groups: young
      healthy subjects (Group 1: mean 29 years, n = 7), aged healthy subjects (Group 2,
      mean 80 years, n = 7), and aged subjects with an important degree of malnutrition
      (Group 3, mean 84.6 years, n = 7). INTERVENTION: Each subject ingested a
      standardized liquid meal after an overnight fast. MAIN OUTCOME MEASURES: Plasma
      cholecystokinin was measured using a sensitive bioassay before and after the
      ingestion of the liquid meal. RESULTS: Basal cholecystokinin levels were similar
      (0.9 to 1 pM equivalent CCK-8) in the three groups. Postprandial levels were
      significantly increased over basal (P less than 0.05). The maximal
      cholecystokinin value was lower in Group 1 (3.5 +/- 0.8 pM equivalent CCK-8) and
      Group 2 (3.3 +/- 0.77 pM equivalent CCK-8) than in Group 3 (8.3 +/- 2 pM
      equivalent CCK-8) (P less than 0.05). Integrated plasma cholecystokinin was also
      similar in Group 1 (171 +/- 38 pM.60 min), (P less than 0.05). CONCLUSION: The
      increase of postprandial maximal levels of cholecystokinin is more related to
      malnutrition than to aging.

PMID- 1372923
TI  - Effects of dibutyrylcyclic adenosine monophosphate on bleomycin-induced lung
      toxicity in hamsters.
AB  - Cyclic nucleotides play an important role in the regulation of fibroblast
      proliferation and collagen metabolism. In the present study, the antifibrotic
      potential of dibutyrylcAMP (Bt2cAMP) was evaluated in the bleomycin (BLM)-hamster
      model of pulmonary fibrosis. Bt2cAMP (10 mg kg-1, s.c.) or saline (SA, s.c.) was
      given daily two days prior to the first intratracheal (i.t.) dose of BLM or SA
      and thereafter throughout the study. BLM or SA was instilled i.t. in three
      consecutive doses (2.5, 2.0 and 1.5 U 5ml-1 kg-1) at weekly intervals. Hamsters
      were killed at 7, 14 and 20 days after the third i.t. instillation. Bt2cAMP
      significantly reduced the contents of lung hydroxyproline and lung thiobarbituric
      acid reactive substance equivalents in BLM-treated animals at 7 and 14 days.
      Bt2cAMP significantly elevated lung superoxide dismutase activity in BLM-treated
      animals at 7 days. Lung prolyl hydroxylase activity was significantly elevated at
      14 and 20 days in SABLM- and Bt2cAMPBLM-treated animals. The ratio of cAMP/cGMP
      was significantly reduced at all time points in SABLM-treated animals but only at
      7 and 14 days in Bt2cAMPBLM-treated animals. Bt2cAMP caused no significant
      changes in lung calcium and calmodulin levels and protein content of the
      bronchoalveolar lavage. BLM significantly increased various inflammatory cell
      counts in the lavage at all three time points. The cell counts in the Bt2cAMPBLM
      groups were generally lower at 7 days and higher at 20 days than those of the
      SABLM groups. Histological evaluation showed that the lungs of Bt2cAMPBLM-treated
      hamsters progressed from an inflammatory cell lesion to a fibrotic lesion at a
      slower rate than the SABLM groups. It was concluded that Bt2cAMP attenuated BLM
      induced pulmonary fibrosis in hamsters in part by delaying the acute phase of the
      inflammatory reaction.

PMID- 1372924
TI  - Large volume paracentesis and intravenous dextran to treat tense ascites.
AB  - Forty patients with cirrhosis of the liver and tense ascites were randomized to
      receive either aldactone 400 mg/day and furosemide 80 mg/day (n = 20) or repeated
      large volume paracentesis (LVP) and infusion of low molecular weight dextran (n =
      20). Both treatment groups were similar in clinical and laboratory parameters.
      Complete mobilization of the ascitic fluid was achieved in all receiving LVP and
      dextran therapy within 1 week of the treatment, in contrast to the minimal
      mobilization of the ascitic fluid in patients receiving diuretics even after 2
      weeks of therapy. Renal function, the clinical parameters of systemic
      hemodynamics, serum electrolytes, and hepatic function remained stable in
      patients receiving LVP and dextran and were similar to those in the diuretic
      treated patients. We found no deterioration of these functions in the
      nonedematous patients treated by LVP and dextran even though the protective
      effect of edema against LVP was lacking in them. Plasma volume estimation in six
      nonedematous cirrhotic patients treated by LVP and dextran did not reveal any
      hypovolemia after complete mobilization of ascites. The frequency of
      complications and death were similar in the two groups. Dextran infusion is a
      safe, effective, and low-cost replacement therapy in patients with cirrhotic
      ascites treated by LVP.

PMID- 1372925
TI  - AIDS-like disproportion of minor T-cell subsets in Japanese patients with
      Wegener's granulomatosis.
AB  - Fifteen Japanese patients with Wegener's granulomatosis (WG) were evaluated
      according to their lymphocyte subset abnormalities. Two colour immunofluorescent
      flow cytometry was used to distinguish the lymphocyte subset alterations. WG
      group showed a decrease in the percentage of CD4+ cells and the increase of CD8+
      cells. Within the NK cell family, the functionally unidentified CD8+57+ cells
      were markedly elevated. The disproportion of the lymphocyte subsets (CD4+
      decreases CD8+57+ increases) were similar to those of Acquired Immunodeficiency
      Syndrome (AIDS) and AIDS relating complexes (ARC). To assess silent infection of
      Human immunodeficiency virus (HIV), the polymerase chain reaction (PCR) was done
      for all patients to selectively amplify specific HIV proviral DNA sequences in
      peripheral blood mononuclear cells, HIV-1 proviral DNA was not found in any
      patients but these changes of WG might suggest a possible adaptive response to
      unknown viral infection.

PMID- 1372926
TI  - Patch-clamp analysis of the effects of the insecticide deltamethrin on insect
      neurones.
AB  - 1. The mode of action of the pyrethroid insecticide deltamethrin on inexcitable
      embryonic cultured cockroach neurones has been investigated using the patch-clamp
      technique. 2. Whole-cell recordings of the current induced by step
      depolarizations of the cell membrane showed that concentrations of deltamethrin
      ranging from 10(-8) to 5 x 10(-6) mol l-1 induced a small tetrodotoxin (TTX)
      sensitive inward current that peaked at around +10 mV and reversed at around +60
      mV. The activation and inactivation kinetics of this current were much slower
      than those of the axonal sodium current in this same species and were relatively
      insensitive to membrane potential. Steady-state inactivation was almost absent.
      3. Single-channel activity associated with the action of the insecticide was
      analyzed using the cell-attached configuration. Three distinct patterns of
      activity were found: (1) discrete single-channel events of relatively short
      duration, (2) long events of comparatively small amplitude and (3) complex bursts
      made up of a succession of openings and closings to several levels. These three
      patterns were analyzed quantitatively using specially designed programs. 4. The
      first pattern of activity could be seen in most patches. It consisted of short (1
      10 ms) rectangular events of comparatively small amplitude (1.5 pA at rest) and
      very low open time probability (around 0.001). The current-voltage relationship
      of these small events was linear over the voltage range studied and the
      (extrapolated) reversal potential approximated ENa. 5. The second pattern of
      activity was observed less frequently. The channels could stay open for very long
      periods (up to several seconds) and occasionally flickered between two or more
      levels. 6. The third pattern of activity was observed in many patches. During the
      burst, which could last from a few milliseconds to a few hundred milliseconds,
      the single-channel current jumped almost continuously between several levels (up
      to 7 or 8).

PMID- 1372927
TI  - Prevalence and geographical distribution of major LDL receptor gene
      rearrangements in Finland.
AB  - In order to determine the prevalence of major rearrangements of the low density
      lipoprotein (LDL) receptor gene in Finland, DNA samples of 199 unrelated Finnish
      patients with the heterozygous form of familial hypercholesterolaemia (FH) were
      examined by Southern blot analysis. The FH-Helsinki mutation, characterized by a
      9.5-kb deletion in the 3'-end of the LDL receptor gene, was found in 75 (38%) of
      the patients. The prevalence of this mutation ranged from 26-58% in different
      areas of Finland. A striking exception was the North Karelia region, where only
      one out of 26 (4%) FH patients was found to carry the FH-Helsinki allele. Two
      patients were found to carry other types of large nucleotide rearrangements of
      the LDL receptor gene. One mutation was a 7.5-kb deletion eliminating exons 7 to
      10, and the other was a 13-kb deletion covering exons 11 to 16 of the LDL
      receptor gene. Serum lipoprotein levels were very similar in each category of
      mutation, i.e. in patients with the FH-Helsinki gene, those with the two other
      types of deletion, and the remaining patients with as yet unknown types of LDL
      receptor gene defects. These results show that, even in genetically uniform
      populations, FH may be heterogeneous at the DNA level. DNA techniques enable an
      unequivocal diagnosis for almost 40% of the Finnish patients with the
      heterozygous form of FH.

PMID- 1372928
TI  - Localization of conserved B-cell epitopes among encapsulated and non-encapsulated
      Haemophilus influenzae P2 porin proteins using synthetic peptides.
AB  - The P2 outer membrane protein of Haemophilus influenzae belongs to a class of
      apparently ubiquitous proteins in Gram-negative bacteria that function as porins.
      Murine hybridomas raised to the P2 protein and synthetic peptides were used to
      investigate the structural and antigenic relationships among P2 proteins of
      encapsulated and non-encapsulated H. influenzae. Three monoclonal antibodies
      (mAbs), P2-17, P2-18 and P2-19, recognizing epitopes on the P2 protein, as shown
      by Western immunoblotting of outer membrane preparations, and purified and
      recombinant P2 proteins are described. The epitopes reactive with the mAbs were
      widely distributed among H. influenzae strains since 70-100% of strains of
      encapsulated and non-encapsulated isolates collected worldwide were recognized by
      individual mAbs. None of the mAbs reacted with H. parainfluenzae or other
      bacterial species. The peptide composition of P2 epitopes was determined by
      analysis of mAb reactivity with a series of overlapping synthetic peptides that
      covered the amino acid sequences of H. influenzae type b. The domains recognized
      by these mAbs were completely distinct. mAb P2-18, reactive with an epitope
      conserved among all H. influenzae P2 porin molecules which were screened,
      recognized a peptide corresponding to the N-terminal segment (residues 1-14). The
      P2-17- and P2-19-specific epitopes were located between residues 28 and 55, and
      101 and 129, respectively. None of the epitopes were exposed on the cell surface
      since no mAbs bound to intact live bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372929
TI  - Diversity of cleavage patterns of Salmonella 23S rRNA.
AB  - The recent discovery of the phenomenon that some prokaryotes fragment their 23S
      rRNA during post-transcriptional processing of precursor rRNA has been shown to
      be particularly prevalent among strains and species of Salmonella. Some strains
      of Salmonella cleaved 23S rRNA at multiple sites producing several fragments. The
      cleavage patterns of 23S rRNA differed among Salmonella strains and sometimes
      among the rRNA operons in the same strain. Fragmentation of 23S rRNA was not
      observed in strains of the closely related species Escherichia coli.
      Fragmentation of 23S rRNA occurred in Brucella and Agrobacterium but the cleavage
      pattern was not as diverse as that demonstrated in Salmonella. Introduction of
      cleavage sites into precursor 23S rRNA of Salmonella is probably a recent
      evolutionary event.

PMID- 1372930
TI  - Identification of indigo-related pigments produced by Escherichia coli containing
      a cloned Rhodococcus gene.
AB  - Pigments produced by Escherichia coli containing a cloned piece of DNA from
      Rhodococcus sp. ATCC 21145 were extracted in chloroform and separated into blue
      and pink components. Evidence from TLC, NMR spectroscopy, absorption spectrum
      analysis and solubility behaviour suggested that the blue pigment was indigo and
      the pink pigment was indirubin, a structural isomer of indigo. The proposed
      pathway for pigment production on LB agar involves the conversion of tryptophan
      to indole by tryptophanase of E. coli and the oxidation of indole to indigo by
      the product of the cloned Rhodococcus DNA insert.

PMID- 1372931
TI  - Visceral targets specify calcitonin gene-related peptide and substance P
      enrichment in trigeminal afferent projections.
AB  - Rat trigeminal ganglion projections to a visceral target (intracranial blood
      vessels) are enriched in calcitonin gene-related peptide (CGRP) and substance P
      (Sub P) compared to trigeminal ganglion projections to a cutaneous target (the
      forehead skin). We asked if transplants of a novel visceral target (fetal stomach
      antrum tissue) into the path of the neonatal rat trigeminal frontal nerve
      projection to forehead skin would induce neuronal CGRP and Sub P enrichment. By
      postnatal day (P) 25, the percentage of nerves containing CGRP increased from 14
      15% in the control trigeminal projection to forehead skin to 20-31% (in different
      experiments) in the trigeminal projection to transplanted stomach antrum. The
      percentage of Sub P-containing neurons increased from 10% in the control forehead
      skin projection to 22% in the trigeminal projection to stomach transplants over
      the same time period. The number of neurons in the trigeminal frontal nerve
      projection to stomach antrum transplants was not significantly different from the
      number of frontal neurons projecting to control forehead skin. We suggest that
      respecification of trigeminal neurons to the CGRP and Sub P phenotype, not
      selective survival of CGRP- and Sub P-positive afferents, is the mechanism by
      which stomach antrum induces enrichment of CGRP and Sub P. A subpopulation of rat
      trigeminal neurons with cutaneous forehead skin projections also sends a
      transient axon collateral projection to a visceral target (the cerebral arteries)
      during early postnatal development. Postnatal maintenance of an axonal projection
      to a cutaneous target (forehead skin) may be incompatible with a neuron also
      maintaining a visceral collateral to the cerebral arteries.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1372932
TI  - Asymmetric modulation of cytosolic cAMP activity induces growth cone turning.
AB  - The possible role of cyclic nucleotides as second messengers mediating growth
      cone turning was studied by producing an asymmetric distribution of cyclic
      nucleotides across the growth cone. A repetitive pulse application method was
      developed to produce microscopic chemical gradients near the growth cone of
      embryonic Xenopus neurons in cell culture. When picoliters of a solution
      containing 20 mM dibutyryl cAMP (dB-cAMP), a membrane-permeable analog of cAMP,
      were repetitively ejected from a micropipette near the growth cone, neurite
      growth was consistently directed toward the pipette. Theoretical analysis of the
      diffusion gradient showed that the neurite is capable of detecting a 10%
      difference in dB-cAMP concentration across the growth cone. Similar responses
      were also observed using gradients of the phosphodiesterase inhibitor
      isobutylmethylxanthine, or of forskolin, which activates adenylate cyclase.
      Dibutyryl cGMP, however, produced no significant turning. These results suggest
      that a cytoplasmic gradient of cAMP across the growth cone is sufficient to
      initiate its turning response, and that cAMP in the growth cone could serve as a
      second messenger in mediating the action of extracellular guidance cues.

PMID- 1372933
TI  - Effect of select media supplements on motility and development of Eimeria
      nieschulzi in vitro.
AB  - A technique was developed to examine the effects of exogenous substances on
      apicomplexan sporozoite motility in vitro. Sporozoites of Eimeria nieschulzi were
      placed in the top compartments of blind well chemotactic chambers and separated
      from potential chemoattractant/chemokinetic agents by 8.0-microns pore size
      Millipore filters. After 3-hr incubations, the number of sporozoites migrating
      through the filters was assessed using a hemacytometer. Results revealed that
      several substances, especially albumin and fetuin, enhanced motility of coccidial
      sporozoites. Cell culture assays supported these data, with higher numbers of
      parasites found in cultures supplemented with albumin and/or fetuin.

PMID- 1372934
TI  - Carbohydrate ligands of the LECAM family as candidates for the development of
      anti-inflammatory compounds.

PMID- 1372935
TI  - Distribution of cytokeratins in oral cytological smears of HIV-infected patients.
AB  - Cytological smears (CS), taken from the lateral border of the tongue of HIV
      seropositive patients (HIV+) (n = 34) and of seronegative controls (HIV-) (n =
      16), were examined by means of immunocytochemistry (APAAP) for the distribution
      patterns of different cytokeratins and MHC class II antigens. Compared with HIV-
      patients in CS of HIV-infected patients cornification associated cytokeratins
      10/11 were increased, while the number of keratinocytes positive for cytokeratins
      13/16 was comparable in both groups. Expression of simple epithelial cytokeratins
      19, rarely observed in CS of HIV- patients, was a frequent findings in CS of HIV+
      patients. Keratinocytes positive for MHC class II antigens were observed in CS of
      12/34 HIV+, while all control CS were negative. In the group of HIV+ patients no
      correlation was found between the clinical presence of HL and the expression of
      cytokeratins or class II antigens. The altered distribution of cytokeratins may
      reflect local responses to proliferative stimuli or local inflammation due to the
      presence of microbial antigens or may occur as a general unspecific reaction in
      the setting of systemic viral infection. This non-invasive technique seems to be
      a valuable tool to determine the proliferation rate of oral epithelial cells.

PMID- 1372936
TI  - Topology of innervation of labial salivary glands by protein gene product 9.5 and
      synaptophysin immunoreactive nerves in patients with Sjogren's syndrome.
AB  - Glandular secretion and integrity, local blood flow, salivary secretion, pain
      perception and neurogenic inflammation can all be controlled by the nervous
      system. Therefore, the pattern of innervation of labial salivary glands (LSG) was
      studied in 10 patients with Sjogren's syndrome using neuronal markers: protein
      gene product 9.5 (PGP 9.5), a cytoplasmic, noncytoskeletal epitope and
      synaptophysin, a glycoprotein present in presynaptic vesicles. PGP 9.5
      immunoreactive nerve fibers were found surrounding the acini, salivary ducts and
      blood vessels. The rich innervation of LSG was even more evident in
      immunofluorescence stained sections analyzed using confocal laser scanning
      imaging. Synaptophysin immunoreactive nerve endings and preterminal varicosities
      also demarcated the LSG acini. Furthermore, in the small foci, PGP 9.5 and
      synaptophysin immunoreactive nerve fibers were found amid inflammatory
      mononuclear cells and in extensive inflammatory areas nerve fibers were found in
      the peripheral parts of such infiltrates. This suggests a possible neurogenic
      influence on the local cellular inflammation. When LSG patient samples were
      compared to unaffected glands from 7 controls, acinar atrophy was found in the
      areas devoid of a local delivery system of neurogenic trophic stimuli, suggesting
      this as a possible cause of glandular degeneration. It may become necessary to
      incorporate this neglected, but existing system into our current view on the
      local but possibly centrally controlled or influenced pathogenetic mechanisms of
      Sjogren's syndrome.

PMID- 1372937
TI  - Metastatic parathyroid carcinoma: a radiological, biochemical and symptomatic
      response to metastectomy.

PMID- 1372938
TI  - Cytoplasmic chloride regulates cation channels in the vacuolar membrane of plant
      cells.
AB  - This study is concerned with the characterization of the ionic currents in the
      vacuolar membrane (tonoplast) of plant cells. Voltage patch-clamp experiments at
      the whole vacuole and single channel levels were employed to study the effects of
      cytoplasmic chloride on the tonoplast inward rectifying currents of sugar beet
      cultured cells. Whole vacuole experiments showed that removal of cytoplasmic
      chloride induced a decrease in the level of the inward currents, an effect that
      was reversed upon returning to control levels of cytoplasmic chloride.
      Substitution of cytoplasmic chloride by any other anion (organic or inorganic)
      resulted in a reduction in the level of the inward currents. At a given negative
      tonoplast potential, the inward currents showed a linear relationship with the
      concentration of cytoplasmic chloride between 10 and 100 mM, with the slope of
      these relationships increasing as the potential was made more negative. Single
      channel experiments showed that reduction of cytoplasmic chloride changed the
      gating mechanism of the channels without affecting the single channel
      conductance. Reduction of cytoplasmic chloride caused a decrease in the open
      probability of the tonoplast cation channels by reducing their mean open time and
      by inducing the appearance of an additional closed state.

PMID- 1372939
TI  - Ion selectivity of colicin E1: modulation by pH and membrane composition.
AB  - Colicin E1 is a plasmid-encoded bacteriocidal protein which, though water soluble
      when secreted by its host bacterium, spontaneously interacts with planar lipid
      bilayers to form voltage-gated ion channels. In asolectin bilayers, the
      preference for anions over cations exhibited by these channels at low pH can be
      reversed by raising the pH on either side of the membrane. When incorporated into
      membranes composed of either of the two zwitterionic lipids, bacterial
      phosphatidylethanolamine and diphytanoyl phosphatidylcholine, colicin E1 channels
      were nearly ideally anion selective in the limit of low pH and moderately cation
      selective at the high pH limit. In phosphatidylcholine membranes, however, the
      response of these channels to changes in pH exhibited a pattern of behavior
      peculiar to this lipid. If the side of the membrane on which the protein had been
      introduced (the cis side) was exposed to pH 4.0, all the channels in the bilayer,
      whether opened or closed, became refractory to further changes in pH. This
      irreversibility has been interpreted as evidence that the selectivity of colicin
      E1 is under the control of a pH-sensitive conformational change. Protonation of
      groups on the cis side of the membrane appear to be essential to the conversion
      to the anion-selective state. These groups are rendered kinetically inaccessible
      to the aqueous phase when the transition takes place in phosphatidylcholine
      membranes.

PMID- 1372940
TI  - Complementary DNA-DNA hybridization in Drosophila.
AB  - We have performed DNA-DNA hybridization experiments among several species of
      Drosophila using the evolutionarily conserved portion of the genome representing
      sequences coding for amino acids of proteins. This was done by using as tracer,
      radioactively labeled complementary DNA that was reverse transcribed from adult
      mRNA. We show that this procedure extends phylogenetically the distance over
      which the technique can be applied to fast-evolving groups such as Drosophila.
      The major phylogenetic conclusions are (1) the subgenus Sophophora is a
      monophyletic lineage; (2) within Sophophora the melanogaster subgroup is closer
      to the obscura group than either group is to the willistoni group; (3) the
      subgenus Drosophila is complex with most major lineages originating deep in the
      phylogeny; the subgenus may not be monophyletic; (4) as with most groups
      classically placed in Drosophila, the Hawaiian Drosophila originate early,
      supporting the notion that this lineage is older than the extant islands; and (5)
      the virilis/repleta lineage is monophyletic within Drosophila.

PMID- 1372941
TI  - Expression of insulinlike growth factor (IGF) and IGF-binding protein genes in
      human lung tumor cell lines.
AB  - BACKGROUND: The presence of multiple, low-molecular-weight, insulinlike growth
      factor (IGF)-binding proteins in lung tumor cell-conditioned medium and lung
      cancer patient serum has been recently reported. PURPOSE: To begin to elucidate
      the genetic basis for these observations, the present study examines the
      expression by lung tumor cell lines of three IGF-binding protein genes, namely,
      IGFBP-1, IGFBP-2, and IGFBP-3. Since IGF-binding proteins are thought to modulate
      the biologic action of the IGFs, the relationship between the expression of IGF
      binding protein genes and the genes encoding IGF-I and IGF-II also has been
      investigated. METHODS: Gene expression was studied in four small-cell lung cancer
      (SCLC) and three non-small-cell lung cancer (NSCLC) cell lines using Northern
      blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR) for
      IGFBP-1. RESULTS: IGFBP-1 gene expression was detected by Northern blot analysis
      in one NSCLC cell line only. However, RT-PCR revealed that the IGFBP-1 gene was
      expressed in all four SCLC cell lines and in two of the three NSCLC lines.
      Northern blot analysis of IGFBP-2 gene expression demonstrated that all lung
      tumor cell lines expressed this gene. A low level of IGFBP-3 gene expression was
      detected in one SCLC cell line and in all three NSCLC cell lines. All lung tumor
      cell lines expressed the IGF-II gene as determined by Northern blot analysis. In
      marked contrast, none of the lines showed evidence of IGF-I gene expression using
      this method. However, RT-PCR revealed a low level of IGF-I gene expression in one
      SCLC and one NSCLC cell line only. CONCLUSIONS: These observations indicate 1)
      that IGF-binding proteins secreted by lung tumors are encoded by at least three
      different genes; 2) that there may be a close association between IGF-II and
      IGFBP-2 gene expression, such that, where there is production of IGF-II, IGFBP-2
      is the principal BP; and 3) that the IGF-II gene is more widely expressed than
      the IGF-I gene in human lung tumor cell lines.

PMID- 1372942
TI  - Longitudinal evaluation of prostate-specific antigen levels in men with and
      without prostate disease.
AB  - OBJECTIVE: To evaluate longitudinal changes in prostate-specific antigen (PSA)
      levels in men with and without prostate disease. DESIGN: Case-control study of
      men with and without prostate disease who were participants in a prospective
      aging study. SETTING: Gerontology Research Center of the National Institute on
      Aging; the Baltimore (Md) Longitudinal Study of Aging. PATIENTS: Sixteen men with
      no prostate disease (control group), 20 men with a histologic diagnosis of benign
      prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate
      cancer. OUTCOME MEASURES: Multiple PSA and androgen determinations on serum
      samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of
      prostate disease. RESULTS: Changes in androgen levels with age did not differ
      between groups. Control subjects did not show a significant change in PSA levels
      with age. There was a significant difference in the age-adjusted rate of change
      in PSA levels between groups (prostate cancer greater than BPH greater than
      control; P less than .01). At 5 years before diagnosis when PSA levels did not
      differ between subjects with BPH and prostate cancer, rate of change in PSA
      levels (0.75 micrograms/L per year) was significantly greater in subjects with
      prostate cancer compared with control subjects and subjects with BPH. Also, rate
      of change in PSA levels distinguished subjects with prostate cancer from subjects
      with BPH and control subjects with a specificity of 90% and 100%, respectively.
      CONCLUSIONS: The most significant factor affecting serum PSA levels with age is
      the development of prostate disease. Rate of change in PSA levels may be a
      sensitive and specific early clinical marker for the development of prostate
      cancer.

PMID- 1372943
TI  - The effect of digital rectal examination on prostate-specific antigen levels.
AB  - OBJECTIVE--To identify the effect of digital rectal examination (DRE) on serum
      prostate-specific antigen (PSA) levels. DESIGN--A prospective trial before and
      after DRE. SETTING--Multicenter outpatient screening program. PATIENTS--A total
      of 2754 healthy men aged 40 years and older who presented to a prostate cancer
      screening program and consented to two phlebotomies. MAIN OUTCOME MEASURE-
      Changes in serum PSA levels after DRE. RESULTS--Patients were divided into four
      groups based on their initial serum PSA levels. The levels were chosen based on
      previous studies that showed different incidences of prostate cancer within these
      groups. The two groups with the lowest initial PSA values (0.1 through 4
      micrograms/L and 4.1 through 10 micrograms/L) were found to have statistically
      insignificant changes in the serum PSA levels after DRE. The group with initial
      PSA levels of 10.1 through 20 micrograms/L had increases in serum PSA values that
      showed a trend toward statistical significance. The group with initial PSA levels
      of greater than 20 micrograms/L had statistically significant increases in serum
      PSA values after DRE. The alterations in serum PSA levels in the two groups with
      the highest PSA values were not clinically important as the patients' clinical
      treatment was not altered. CONCLUSIONS--No clinically important effects on serum
      PSA levels were noted after DRE.

PMID- 1372944
TI  - Decisions near the end of life. Council on Ethical and Judicial Affairs, American
      Medical Association.

PMID- 1372945
TI  - Prostate-specific antigen. Improving its ability to diagnose early prostate
      cancer.

PMID- 1372946
TI  - The dipeptide alanyl-glutamine prevents intestinal mucosal atrophy in
      parenterally fed rats.
AB  - This study was performed to determine whether the addition of alanyl-glutamine
      (Ala-Gln) can prevent intestinal mucosal atrophy induced by standard solution of
      total parenteral nutrition (S-TPN). Forty-one male Sprague-Dawley rats weighing
      250 g were randomly divided into four groups: group I was killed after overnight
      fasting; group II received S-TPN. The other groups received S-TPN supplemented
      with amino acids other than glutamine (group III) or supplemented with Ala-Gln 2
      g/100 mL (group IV); both solutions were isocaloric and isonitrogenous. After 1
      week of TPN the rats were killed, and the duodenum, proximal jejunum, mid-small
      bowel, and distal ileum were obtained for morphologic and functional analysis.
      Weight gain did not differ significantly among these four groups, and there was
      no difference in nitrogen balance between groups III and IV. Serum glutamine in
      group IV (102.8 +/- 13.3 mumol/dL) was significantly increased (p less than .05)
      compared with groups I, II, and III (66.2 +/- 3.9, 55.7 +/- 7.8, and 61.3 +/-
      10.8 mumol/dL, respectively). Mucosal wet weight, protein, RNA, sucrase, and
      maltase of group IV were significantly increased (p less than .05) compared with
      groups II and III. Villus height was significantly increased (p less than .05) in
      the jejunum of group IV rats compared with groups II and III, but not in any
      other segments of the intestine. No significant changes were observed in crypt
      depth among all groups. Diamine oxidase in groups II, III, and IV was
      significantly decreased (p less than .05) compared with group I in all segments
      except for the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372947
TI  - [Congenital pelvic arteriovenous fistula in a male. A case report].
AB  - A congenital arteriovenous fistula (AV fistula) in the true pelvis is extremely
      rare, especially in males. We present a case of this disease with pollakiuria and
      intrarectal discomfort. Diagnosis was made by computed tomography and magnetic
      resonance imaging and confirmed by cine angiography. Because the AV fistula
      involved the bladder, prostate and rectum, ligation of the main feeding arteries
      was performed. He also had benign prostatic hypertrophy and was treated by
      conservative therapy because of a high risk of massive bleeding in surgical
      treatment.

PMID- 1372948
TI  - HCV confirmatory testing of blood donors.

PMID- 1372949
TI  - Gastrointestinal function in obesity: motility, secretion, and absorption
      following a liquid test meal.
AB  - Digestive responses to a 300-mL liquid fat-rich meal (432 kcal) in a group of
      massively obese patients were compared with those observed in a group of healthy
      lean subjects of variable body weight. Gastric and intestinal propulsion,
      digestive secretions, and absorption in the proximal 70 cm of intestine were
      measured using a multiple-marker dilution method. The average gastric emptying of
      energy, acid, volumes, and meal marker were similar in the two groups 80 minutes
      after intake, justifying a comparison of intestinal processing of the meal.
      Compared with lean subjects, the obese subjects responded with less pancreatic
      secretion (P less than .05) and gallbladder emptying, but absorbed a larger
      proportion of the emptied energy in the test segment (P less than .01) during a
      similar or shorter transit time. In addition, when the entire meals were
      compared, the obese group generally absorbed the test meal more effectively and
      rapidly in the upper part of the intestine. As a consequence, the flow volumes at
      the exit of the test segment were lower (P less than .05), and less of the test
      meal was propulsed to distal parts of the intestine. In the lean subjects, the
      body weight or height correlated positively with the gastric emptying rate, peak
      gastric acid output, and pancreatic responses, and negatively with (P less than
      .05) the segment transit time. The taller the subject, the greater the proportion
      of the meal which was rapidly propulsed unabsorbed to lower parts of the
      intestine, indicating that a large intestinal area was exposed for rapid energy
      uptake. No such correlations were observed in the obese group.

PMID- 1372950
TI  - Treatment of ventricular arrhythmias after CAST.
AB  - OBJECTIVE: The primary objective of this article is to review the management of
      ventricular arrythmias in the light of the unfavourable results reported in the
      Cardiac Arrhythmia Suppression Trial (CAST). STUDY SELECTION, DATA EXTRACTION AND
      SYNTHESIS: CAST tested the hypothesis that suppression of ventricular arrhythmias
      recorded on a Holter monitor in patients with myocardial infarction would lead to
      a decrease in subsequent mortality, presumably by preventing sudden death. In the
      trial, patients with a myocardial infarction which occurred six days to two years
      previously and with asymptomatic ventricular premature beats which could be
      suppressed by one of the antiarrhythmic agents flecainide, encainide or
      moricizine, were randomised to treatment with one of these agents or placebo.
      Over a mean follow-up period of 10 months, mortality was significantly higher in
      those patients receiving flecainide or encainide than in those receiving placebo.
      On the recommendation of the Data and Safety Monitoring Board the trial in these
      groups was terminated. More recently CAST II in which moricizine was compared to
      placebo was also terminated, again because of a higher mortality in the patients
      receiving active treatment. It is likely that much of the excess mortality can be
      attributed to proarrhythmic effects of the agents. CONCLUSION: Current management
      of ventricular arrhythmias are considered in the light of these findings. CAST
      suggests that specific treatment should be dictated by the presence of associated
      symptoms and as much by associated structural heart disease as the arrhythmia per
      se. In particular, specific treatment of ventricular premature beats alone should
      be avoided. In those with potentially lethal ventricular arrhythmias, referral
      for appropriate investigation and consideration of non-pharmacological measures
      is necessary.

PMID- 1372951
TI  - The surveillance challenge: final stages of eradication of poliomyelitis in the
      Americas.
AB  - Current levels of surveillance have contributed to substantial reductions in
      morbidity and mortality due to poliomyelitis in the Americas. Despite the success
      of the poliomyelitis eradication initiative, it has become critical that
      surveillance be intensified so that the absence of wild poliovirus circulation
      can be verified with confidence in countries not reporting confirmed cases of
      poliomyelitis. Cases of acute flaccid paralysis continue to be classified as
      compatible with poliomyelitis, because investigations of such patients do not
      provide sufficient information to rule out wild poliovirus as the cause of
      paralysis. At this stage of the eradication initiative, the presence of
      compatible cases in some countries in Latin America indicates a failure of the
      surveillance system. The greatest challenge for the eradication initiative may be
      correcting the remaining deficiencies of the existing surveillance system that
      hinder efforts to verify that wild poliovirus is no longer being transmitted in
      the Americas.

PMID- 1372952
TI  - Light-regulated expression of the psbD gene family in Synechococcus sp. strain
      PCC 7942: evidence for the role of duplicated psbD genes in cyanobacteria.
AB  - The genome of the cyanobacterium Synechococcus sp. strain PCC 7942 contains two
      psbD genes encoding the D2 protein of the photosystem II reaction center: psbDI,
      which is cotranscribed as a discistronic message with psbC (the gene encoding
      CP43, a chlorophyll-a binding protein), and psbDII, which is monocistronic.
      Northern blot analysis of psbD transcripts showed that the two genes responded
      differently when wild-type cells were shifted from moderate to high light
      intensity. Whereas psbDII transcripts increased 500% relative to unshifted
      control cells, psbDI-psbC transcripts remained unchanged. The beta-galactosidase
      activities expressed from translational fusions between the psbD genes and the
      Escherichia coli lacZ reporter gene displayed responses similar to those seen in
      the RNA. D2 protein levels in thylakoid membranes from wild-type cells increased
      to 250% of those of the unshifted control cells 12 h after a shift to high light
      intensities. In contrast, in a mutant strain (AMC016) that carries an inactive
      psbDII gene, D2 levels decreased by 50% under identical conditions. These results
      suggested that induction of psbDII gene expression by light can serve as a
      supplementary system for maintaining a functional photosystem II reaction center
      at high light intensity. This hypothesis was corroborated by mixed-culture
      experiments, in which AMC016 cells competed poorly with wild-type cells at high
      light intensity. These data suggest for the first time that differential
      expression of members of a cyanobacterial gene family serves to maintain a
      functional PSII reaction center under diverse environmental conditions.

PMID- 1372953
TI  - The coxII gene in carrot mitochondria contains two introns.
AB  - The gene for cytochrome oxidase subunit II (coxII) in carrot is encoded by a
      unique locus in the mitochondrial genome. In contrast to the coxII genes in the
      numerous other plant species investigated to date, the coding region is
      interrupted by two group II introns. The carrot 5' intron is the homologue of the
      single intervening sequence found in several monocot and dicot coxII genes.
      Sequences similar to the 3' intron of the carrot coxII gene have not been
      reported previously and are not detectable by hybridization with Oenothera mtDNA.
      Northern hybridizations indicate complex precursor transcript patterns with mRNA
      molecules up to 10 kb length. The excised intron sequences appear to be stably
      maintained in the mRNA pool. Amino acid sequence comparisons suggest that the
      carrot coxII mRNA needs to be edited by numerous C to U transitions.

PMID- 1372954
TI  - Characterization of interactions involving anti-metatype antibodies and immune
      complexes.
AB  - Immunizations of high affinity anti-fluorescein monoclonal antibody 4-4-20
      affinity labeled with fluorescein 5-isothiocyanate into a rabbit elicited
      antibodies specific for the liganded conformation of 4-4-20 (termed "anti
      metatype" antibodies). Reaction of liganded 4-4-20 with anti-metatype antibodies
      caused significant delay (up to 23-fold) in the rate of dissociation of
      fluorescein ligand from the active site. In this study, structural analogues of
      fluorescein, including fluorescein 5-isothiocyanate, fluorescein 6
      isothiocyanate, 5-dichlorotriazinyl aminofluorescein and 5-carboxyfluorescein,
      were bound by monoclonal antibody 4-4-20 and anti-metatype antibody reactivity
      was observed through delay in the dissociation rate of ligand from Mab 4-4-20.
      Significant delays (ranging from 5- to 242-fold) were observed for all structural
      analogues examined indicating that 4-4-20 maintained similar but not necessarily
      identical conformations upon binding fluorescein structural analogues.
      Additionally, fluorescein 5-isothiocyanate and fluorescein 6-isothiocyanate were
      conjugated to carrier molecules of increasing mol. wt (ranging from 225 to 14,600
      D) in an attempt to sterically interfere with "metatopes" at the mouth of the
      active site and localize regions of anti-metatype antibody binding. These
      fluorescein-conjugated compounds were reacted with 4-4-20, and binding of anti
      metatype antibodies delayed dissociation rates from 24- to greater than 1500
      fold. These results indicated that the mechanism whereby anti-metatype antibodies
      delay the release of fluorescyl ligands from the active site probably does not
      solely involve steric hindrance of the ligand due to binding of anti-metatype
      antibodies at the mouth of the active site. Studies with 4-4-20 Fab fragments and
      a single chain derivative of 4-4-20 (consisting of the variable regions tethered
      by a 14 amino acid linker) indicated that anti-metatype reactivity was specific
      for the immunoglobulin variable region.

PMID- 1372955
TI  - Sequence and length heterogeneity of alpha Fc gamma R transcripts in AKR mice.
AB  - The murine low-affinity receptors for IgG, Fc gamma RIII and Fc gamma RII, are
      encoded by the alpha and the beta Fc gamma R genes, respectively. By contrast to
      the sequence and the molecular polymorphism of human Fc gamma RIII, no
      heterogeneity of the murine Fc gamma RIII has been reported and a single alpha Fc
      gamma R transcript was observed. We describe here a double heterogeneity of alpha
      Fc gamma R transcripts. First, by S1 mapping of alpha transcripts and by cloning
      of cDNA coding for Fc gamma RIII, we found a strain-related sequence
      heterogeneity: four amino acids in the coding region and two stretches of
      nucleotides in the 3' untranslated sequences differ between alpha transcripts of
      AKR and BALB/c mice. Second, in AKR mice, we found a cell-dependent length
      heterogeneity: a short 0.9 kb alpha transcript was present in peritoneal
      thioglycolate-elicited cells (PEC) from AKR mice. This transcript was present
      neither in mast cells and NK cells from AKR and BALB/c mice nor in PEC from
      BALB/c mice. A short cDNA, with a deletion of all the 3' untranslated sequences,
      has been cloned from AKR PEC, and corresponds to the short alpha transcript. All
      the differences found in the 3' untranslated sequences of AKR alpha transcripts
      are located within the fifth exon of the mouse alpha Fc gamma R gene.

PMID- 1372956
TI  - C1-inhibitor prevents PEG fractionation-induced, EDTA-resistant activation of
      mouse complement.
AB  - Fractionation of mouse serum by precipitation with a critical amount of
      polyethylene glycol 6000 (PEG; 11% w/v) results in a classical and alternative
      pathway-independent activation of the terminal complement route. The activation
      can take place after the separation of an activating principle together with the
      terminal route components from a natural regulator. The isolation and
      identification of the regulatory component preventing this activation in serum,
      is subject of this paper. The regulator was purified by fractionated PEG
      precipitation (15-25%), followed by heparin-Sepharose affinity, Mono Q anion
      exchange, and Superose 12 gel filtration chromatography. The regulator appeared
      to be a single-chain protein with a Mr of 96 k. A protein with similar activity
      purified from human serum had a Mr of 104 k and was functionally and
      antigenically indistinguishable from C1-INH. The mouse 96 k protein inhibited C1
      esterase activity indicating that this protein is indeed C1-INH. Mouse C1-INH
      regulates the PEG fractionation-induced bypass activation of complement, but does
      not interfere with the assembly or the lytic activity of membrane attack
      complexes. alpha 2-Macroglobulin appeared also to be capable of inhibiting the
      PEG-precipitation-induced activation process, but with lower efficiency.

PMID- 1372957
TI  - Functional analysis of interferon-alpha subtypes using monoclonal antibodies to
      interferon-alpha 4a--subtype reactivity, neutralisation of biological activities
      and epitope analysis.
AB  - A panel of monoclonal antibodies (mAb) to a major human interferon-alpha (IFN
      alpha) subtype, -alpha 4a, have been produced, characterised and used for studies
      of structure/function relationships of IFN-alpha subtypes. The mAb were tested
      for effects on receptor binding of IFN-alpha 4a, reactivity with other major
      subtypes -alpha 1, -alpha 2b and -alpha 14 by competitive ELISA and western
      immunoblotting, and for neutralisation of antiviral and antiproliferative
      activities of the four subtypes. The mAb could be grouped according to reactivity
      with IFN-alpha subtypes, group I (designated I-4-A) reacted with -alpha 4a and 
      alpha 2b, group II (I-4-C and I-4-F) reacted with -alpha 4a and -alpha 1, group
      III (I-4-D), I-4-G and I-4-H) reacted with -alpha 4a only, whereas group IV (I-4
      I) reacted with -alpha 4a, -alpha 1 and -alpha 2b. No mAb reacted with IFN-alpha
      14. Sequence comparisons of reactive and non-reactive IFN-alpha subtypes, and
      reactivity patterns with IFN-alpha fragments obtained by Lys-C digestion
      indicated that the epitopes were located in the N-terminal region (group I), in
      two regions of the middle of the molecule (group III and IV) and in the C
      terminal region (group II). Binding of mAb to any of these four distinct epitopes
      neutralised the biological activities of IFN-alpha 4a, and in all cases, except I
      4-A, inhibited receptor binding. Only the group III mAb bind to an epitope
      proposed to be in the vicinity of residues 30-40 which are implicated, from in
      vitro mutagenesis studies, in receptor binding. Binding of mAb to the other 3
      epitopes neutralises biological activities by indirect mechanisms. These results
      emphasise the antigenic diversity between highly homologous IFN-alpha subtypes,
      which may have a wider functional significance. Individual mAb will have
      practical applications in the purification and detection of several IFN-alpha
      subtypes and so facilitate their further characterisation. By virtue of their
      different mechanisms of neutralisation, this panel of mAb will be useful in
      further studies of receptor interaction and signal transduction by IFN-alpha, and
      illustrate principles which are relevant to immunochemical studies of the
      receptor interactions of other cytokines.

PMID- 1372958
TI  - Continuing V gamma 2 to J gamma 2 rearrangements of murine T cell receptor gamma
      genes in a B-committed immature cell line.
AB  - In SPL2-1-2, a murine B-committed immature cell line transformed with a
      temperature-sensitive mutant of Abelson virus, T cell receptor (TCR) gamma gene
      rearrangements, together with IgH gene rearrangements, were induced during
      culture at a non-permissive temperature (39 degrees C). During 11-12 months of
      culture, TCR gamma gene rearrangements occurred in all cells. In contrast to TCR
      gamma genes, neither TCR beta or TCR delta were detected even after 11-12 months
      of culture at a non-permissive temperature. The majority of the TCR gamma gene
      rearrangements observed here were V gamma 2 to J gamma 2 joinings and the
      remaining rearrangements were J gamma 1-linked. V gamma 1 to J gamma 4 and V
      gamma 3 to J gamma 3 joinings were not detected. Approximately 70% of cells with
      TCR gamma gene rearrangements produced normal-sized transcripts from the
      rearranged TCR gamma genes. Cloning and sequencing analysis of a cDNA from the
      transcripts demonstrated that the whole structure of the cDNA was similar to that
      of T-lineage cells. These results showed that TCR gene rearrangements were
      restricted to the gamma genes and that V gamma 2 to J gamma 2 joinings occurred
      preferentially in this B-committed immature cell line. Furthermore, TCR gamma
      gene rearrangements also occurred in intracytoplasmic mu-chain producing cells.
      This indicated that the existence of intracytoplasmic mu-chains did not prevent
      TCR gamma gene rearrangements, although the existence of mu-chains is known to
      inhibit further productive IgH gene rearrangements, (allelic exclusion). These
      results should provide many implications for the mechanism of TCR gene
      rearrangements, especially that of cross-lineage rearrangements.

PMID- 1372959
TI  - Identification and characterization of a partial cDNA expressing interleukin-1
      like activity in keratinocytes.
AB  - A partial cDNA has been isolated from the human keratinocyte cell line COLO-16
      which is distinct from either IL-1 alpha or beta and encodes a protein which
      displays some of the biological properties associated with IL-1. The 720 bp
      partial cDNA hybridized on Northern blots of COLO-16 mRNA to a 1.6 kbp message of
      low abundance. Expression of the partial cDNA in COS-1 cells resulted in activity
      in three IL-1 assays: thymocyte co-stimulation, D10.G4.1 T-cell stimulation and
      fibroblast proliferation. Antisera generated against synthetic peptides based on
      inferred protein sequence from the cDNA reacted with a 20 kDa and 30 kDa species
      in both the COLO-16 cell line and PMA-stimulated normal human keratinocytes.
      These novel species were also present in PMA-stimulated and unstimulated human
      dermal fibroblasts and human T-cell lines.

PMID- 1372960
TI  - Permanent bruxism as a manifestation of the oculo-facial syndrome related to
      systemic Whipple's disease.
AB  - We report here a new case of oculomasticatory syndrome related to systemic
      Whipple's disease. The patient presented typical ophthalmoparesis associated with
      ocular myorhythmia consisting of 1 Hz convergent oscillations of both eyes. The
      masticatory involvement was remarkable and consisted of a permanent bruxism
      leading to severe tooth abrasions. Possible pathophysiology of such a disorder is
      discussed.

PMID- 1372961
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. A method for combining and comparing short-term genotoxicity test
      data: preface. A report from ICPEMC Committee 1.

PMID- 1372962
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. A method for comparing and combining short-term genotoxicity test
      data: the optimal use of dose information.

PMID- 1372963
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. A method for comparing and combining short-term genotoxicity test
      data: results and interpretation.

PMID- 1372964
TI  - International Commission for Protection Against Environmental Mutagens and
      Carcinogens. A method for comparing and combining short-term genotoxicity test
      data: the basic system.

PMID- 1372965
TI  - Myasthenogenicity of a human acetylcholine receptor alpha-subunit peptide:
      morphology and immunology.
AB  - Each of 10 rats inoculated with a synthetic peptide comprising residues 125-147
      (without a disulfide bond) of human acetylcholine receptor (AChR) alpha-subunit
      (H alpha) had deposits of IgG and C3 (immune complexes) and showed morphological
      changes in the fine structure at the motor end-plates 5 weeks after a single
      immunization. Antibody to the H alpha peptides was elevated 1 week after
      immunization, but, antibody levels to solubilized human or rat AChR were very low
      in 8 of the 10 rats. These results suggest that the immune response to peptide H
      alpha is the myasthenogenic site, which induces morphological change at the end
      plates.

PMID- 1372966
TI  - Chromogranin A epitopes: clues from synthetic peptides and peptide mapping.
AB  - Chromogranin A (CgA) is a 48 kDa acidic protein in neuroendocrine secretory
      vesicles whose primary structure is now known. We used synthetic peptides,
      synthetic peptide antisera, intact molecule antisera, chymotryptic peptide
      mapping, microsequencing, immunoblotting, and immunoprecipitation to probe the
      location of immunodominant domains within the CgA molecule. Polyclonal anti mid
      molecule, anti N-terminal and anti C-terminal antibodies specifically visualized
      CgA (both bovine and human) in one and two dimensional immunoblots of adrenal
      chromaffin vesicles, and the stain CgA fragments further suggested bidirectional
      (both N- and C-terminal) cleavage or processing of CgA. Anti intact CgA
      immunoblotting of HPLC-separated peptides from chymotrypsin-digested bovine CgA
      revealed several strongly immunoreactive internal peptides, two of which were
      positioned by N-terminal amino acid sequencing: CgA91ff. and CgA197ff.. A single
      synthetic peptide (CgA79-113) was recognized by three antibodies developed
      against the intact CgA molecule: two polyclonal rabbit antisera as well as a
      monoclonal mouse antibody. Not all antigenicity algorithm-predicted domains were
      immunogenic, suggesting that some of these predicted domains may not be
      accessible. Polyclonal anti mid-molecule, anti N- and anti C-terminal synthetic
      peptide antisera specifically immunoprecipitated 125I-labeled bovine CgA from
      aqueous solution; mid-molecule antisera precipitated substantially greater
      amounts than terminal antisera. The immunoprecipitation results suggested exposed
      terminal as well as interior hydrophilic epitopes in the molecule in its intact,
      native conformation. 125I-human CgA was best precipitated by anti N-terminal
      antisera, consistent with greatest interspecies sequence conservation at the N
      terminus of CgA. The terminal antisera reacted immunohistochemically in a
      granular pattern with adrenal medullary chromaffin cells (but not adrenal
      cortical cells) and pancreatic islet cells (but not pancreatic exocrine acini).
      Thus, synthetic and chymotryptic peptides yielded novel and specific insights
      into the structure, conformation, vesicular processing and interior
      immunodominant domains of CgA.

PMID- 1372967
TI  - Evidence of NK1 and NK2 tachykinin receptors and their involvement in histamine
      release in a murine mast cell line.
AB  - Binding of [3H]substance P (SP) and histamine release were examined using a
      cloned mouse mast cell line. SP binding was saturable and specific. In the
      presence of 30 mM Na2SO4/50 mM Tris buffer, SP interacted with two types of
      binding sites with Kd values of 0.3 and 40 nM. High-affinity SP binding was
      blocked by the inclusion of 0.5 uM of the NK1 receptor selective ligand septide
      in the binding mixture. Neurokinin A (NKA) evoked concentration-dependent
      histamine release. At concentrations in the nanomolar range, the NK1 preferring
      agonists SP, SP methylester and physalaemin evoked less than or equal to 5% net
      release of histamine, which was substantially less than the maximum effect of NKA
      (+37%) in the micromolar range. Pretreatment of the cells with the NK2 antagonist
      peptide A reduced NKA-induced histamine release. [D-Arg1,D-Phe5,D-Trp7,9,Leu11]
      substance P, a putative SP antagonist, also elicited histamine release in the
      micromolar range, apparently acting as an agonist at the NK2 site. Compound
      48/80, N-terminal SP fragments, neurokinin B and the two selective NK2 receptor
      antagonists cyclo(Gln-Trp-Phe-(R)-[ANC-2]Leu-Met) (peptide A) and cyclo(Gln-Trp
      Phe-Gly-Leu-Met) (peptide B) were ineffective. Although the results suggest the
      coexistence of functional NK1 and NK2 receptors, it appears that in this mast
      cell line neurokinin-induced histamine release is primarily mediated by the NK2
      receptor, characterized biochemically as a low affinity binding site with a Kd
      value of 40 nM for SP.

PMID- 1372968
TI  - Is the morphology of ventricular premature beats a marker for left ventricular
      dysfunction?
AB  - The morphology of ventricular premature beats has been described as a marker for
      the presence or absence of myocardial disease. Furthermore, the premature beat
      has been reported to be a potential marker for a dilated and hypokinetic left
      ventricle. To verify this previously tested hypothesis, 37 healthy patients with
      ventricular premature beats on an electrocardiogram (ECG), Holter monitor ECG, or
      a stress test ECG were classified according to the ventricular premature beat
      morphology. Group 1 had ventricular premature beat QRS complexes with a smooth
      contour or with narrow (less than 40 msec) notching. Group 2 had ventricular
      premature beats with broad (greater than 40 msec) notching or shelves. All of
      these patients had normal or borderline normal ECGs and normal multiple-gated
      acquisition (MUGA) scans. Nine patients had type 1 ventricular premature beats,
      20 patients had type II ventricular premature beats, and eight patients had both
      type I and type II ventricular premature beats. We conclude that the presence of
      group 2 ventricular premature beats is so frequent in patients with normal left
      ventricular ejection fractions that the use of this marker in identifying
      abnormal left ventricular function is suspect.

PMID- 1372969
TI  - [Treatment of carcinoid syndrome with a somatostatin analogue].
AB  - Octreotide, a long-acting somatostatin analogue has recently been introduced in
      the therapy of gastroenteropancreatic endocrine tumors, but home experience has
      been lacking. With the aim of drawing attention to this therapeutic possibility,
      a case of malignant carcinoid syndrome treated with octreotide for 18 months is
      reported. Despite the therapeutic attempts preceding the octreotide
      administration a gradual progression in clinical symptoms was observed and
      cardiac failure due to fibrotic and valvular heart disease developed. Cytotoxic
      chemotherapy, serotonin antagonists or repeated selective embolisation of the
      hepatic artery only resulted in a short transitional improvement. Octreotide in a
      dose of 100 micrograms three times daily by subcutaneous injection provided
      effective and rapid relief from episodic flushing and serious diarrhoea. Plasma
      level of serotonin and 24-hour urinary excretion of 5-hydroxyindolacetic acid
      decreased from 6 micrograms/ml to 2 micrograms/ml and from 800 mumol/day to 70
      mumol/day, respectively. No changes in the number and extension of liver
      metastases could be seen after introducing the octreotide treatment. The
      patient's compensated cardiac status could be preserved and continuous therapy
      provided an acceptable quality of life.

PMID- 1372970
TI  - A multiple-source method for studying the prevalence of developmental
      disabilities in children: the Metropolitan Atlanta Developmental Disabilities
      Study.
AB  - The Metropolitan Atlanta Developmental Disabilities Study is the first US,
      population-based epidemiologic study of the prevalence of mental retardation,
      cerebral palsy, hearing impairment, and visual impairment among school-age
      children. The study population consisted of children who were 10 years of age
      between 1985 and 1987 and whose mothers were residents of the five Georgia
      counties of Clayton, Cobb, DeKalb, Fulton, and Gwinnett at the time of the
      child's birth. Since children with developmental disabilities are identified by
      and receive services from various health, social service, and education systems,
      a multiple-source case identification method was used. This study is unique in
      that individual school records were used to identify children with the four
      disabilities. Use of a multiple-source method made it possible to confirm
      specific conditions and to classify subtypes of disabilities. About 95% of the
      children with one or more of these four disabilities were initially identified
      through the school systems. This approach is much less costly than conducting
      medical and psychologic assessments on populations of children. In addition, this
      method made it possible to estimate accurately the "administrative prevalence" of
      these disabilities (ie, the number of children previously identified with these
      disabilities for the purpose of providing services). The prevalence rates found
      in this study, per 1000 10-year-old children, were as follows: mental
      retardation, 10.3; cerebral palsy, 2.0; hearing impairment, 1.0; and visual
      impairment, 0.6.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1372971
TI  - Lead toxicity in the 21st century: will we still be treating it?

PMID- 1372972
TI  - Origin of raised maternal serum alpha-fetoprotein levels in second-trimester
      oligohydramnios.
AB  - Concanavalin A (Con A) subtyping of alpha-fetoprotein (AFP) revealed higher
      concentrations of AFP non-reactive with Con A in sera of 12 pregnant women with
      second-trimester oligohydramnios and raised total serum AFP levels than in sera
      of 42 pregnant women with raised total serum AFP levels and a normal amniotic
      fluid volume. This suggests that in oligohydramnios the origin of excess AFP in
      the maternal compartment is amniotic fluid. It is proposed that oligohydramnios
      and the associated raised maternal serum AFP levels are caused by damage of the
      fetal membranes prior to 16 weeks of gestation resulting in leakage of amniotic
      fluid to the decidual tissue and resorption in the maternal circulation.

PMID- 1372973
TI  - Can gestational dates routinely derived from very early ultrasound be used to
      interpret maternal serum alpha-fetoprotein measurements?
AB  - This study assesses the reliability of estimating gestational age via crown-rump
      or gestational sac measurements obtained at 8 weeks' gestation or earlier as part
      of routine physician office practice. To accomplish this, we studied 88
      pregnancies managed at 45 different sites in which both an early first-trimester
      ultrasonically-derived gestational age estimate and a second-trimester biparietal
      diameter (BPD) estimate were available. The first- and second-trimester
      determinations were highly correlated, but the first-trimester determinations
      were, on average, 0.43 weeks earlier than the second. The first-trimester
      estimates were satisfactory for use in interpreting maternal serum alpha
      fetoprotein (MSAFP) screening measurements, but second-trimester BPD measurements
      obtained prior to MSAFP screening should be the method of choice for interpreting
      MSAFP values, due to the increased sensitivity for detecting open spina bifida.

PMID- 1372974
TI  - Not all chorioangiomas are associated with elevated maternal serum alpha
      fetoprotein.

PMID- 1372975
TI  - [Mediators and neuromediators in asthma].
AB  - The physiopathological mechanisms underlying the multifactorial syndrome that is
      asthma are very complex and protean. Most probably, they are genetically
      determined, but they are largely modulated by the environment and by the
      inflammation of bronchi in which allergy occupies a special place. Chemical
      mediators of cellular origin interact with each other and with the cells that
      live or are recruited in the airways. Among these mediators histamine and
      arachidonic acid metabolites seem to play a predominant role, but the clinical
      use of antagonists has not confirmed the data obtained in vitro and in vivo in
      animals and even man. Cytotoxic mediators (cationic proteins, free oxygen
      radicals) are though to exert their noxious effect directly on the bronchial
      epithelium. No single neuromediator of the adrenergic and cholinergic system can
      explain the dysfunctions observed in asthma. Mediators of the non-adrenergic non
      cholinergic system seem to be more interesting owing to their potential
      interaction with cells and with chemical mediators which contribute to the
      development of a true neurogenic inflammation.

PMID- 1372976
TI  - [Value of MACOP B polychemotherapy for malignant non-Hodgkin's lymphomas in AIDS
      infected patients].

PMID- 1372977
TI  - Adherence of pathogenic and non-pathogenic Entamoeba histolytica strains to
      neutrophils.
AB  - The adherence of polymorphonuclear leukocytes (PMNs) to eight pathogenic and nine
      nonpathogenic strains of Entamoeba histolytica was examined. No difference
      between pathogenic and nonpathogenic strains was found. The addition of different
      carbohydrates confirmed the importance of the 170-kDa lectin of E. histolytica in
      binding to PMNs, corroborated by the finding that treatment of PMNs with
      galactosidase inhibited adherence. Inhibition of the microfilament system of E.
      histolytica using cytochalasin B resulted in a loss of adherence to PMNs.
      Inhibition of the microtubule system using nocodazole did not affect adherence.
      Preincubation of the trophozoites with serum resulted in enhanced adherence, but
      the serum factor responsible for this effect could not be identified.
      Fibronectin, vitronectin, integrins (CD11/CD18 molecules), complement, and
      mannose-binding protein did not seem to mediate adherence between E. histolytica
      and PMNs. In summary, these results indicate that defective adherence mechanisms
      are not a common feature of nonpathogenic E. histolytica strains.

PMID- 1372978
TI  - Perfusion with anti-insulin gamma globulin indicates a B to A to D cellular
      perfusion sequence in the pancreas of the rhesus monkey, Macaca mulatta.
AB  - The cellular sequence of intraislet vascular perfusion has been shown to be
      important in the regulation of islet hormone secretion in the rat and dog islet.
      In order to test whether a B to A to D sequence of islet cellular perfusion is
      also present in a nonhuman primate, pancreata from the rhesus monkey, Macaca
      mulatta, were isolated and perfused in vitro in the presence and absence of anti
      insulin gamma globulin. In the presence of the insulin antibody, efflux
      concentration of insulin decreased rapidly (-95 +/- 1.8%), whereas glucagon and
      somatostatin concentrations increased (111 +/- 28% and 239 +/- 38%,
      respectively). These results suggest the presence of a B-A-D cellular sequence of
      vascular perfusion within the monkey islet. The present results also strongly
      support the hypothesis that a B-A-D sequence of islet perfusion is important in
      the regulation of islet hormone secretion and further emphasize the central role
      of the B-cell in intraislet cellular interactions. The results also suggest that,
      despite differences in islet anatomy, a B-A-D order of islet cellular perfusion
      may be the preferred functional sequence among mammalian species.

PMID- 1372979
TI  - A method for determining the positions of polar hydrogens added to a protein
      structure that maximizes protein hydrogen bonding.
AB  - An automated method for the optimal placement of polar hydrogens in a protein
      structure is described. This method treats the polar, side chain hydrogens of
      lysine, serine, threonine, and tyrosine and the amino terminus of a protein. The
      program, called NETWORK, divides the potential hydrogen-bonding pairs of a
      protein into groups of interacting donors and acceptors. A search is conducted on
      each of the local groups to find an arrangement which forms the most hydrogen
      bonds. If two or more arrangements have the same number of hydrogen bonds, the
      arrangement with the shortest set of hydrogen bonds is selected. The polar
      hydrogens of the histidyl side chain are specifically treated, and the ionization
      state of this residue is allowed to change, if this change results in additional
      hydrogen bonds for the local group. The program will accept Protein Data Bank as
      well as Biosym-format coordinate files. Input and output routines can be easily
      modified to accept other coordinate file formats. The predictions from this
      method are compared to known hydrogen positions for bovine pancreatic trypsin
      inhibitor, insulin, RNase-A, and trypsin for which the neutron diffraction
      structures have been determined. The usefulness of this program is further
      demonstrated by a comparison of molecular dynamics simulations for the enzyme
      cytochrome P-450cam with and without using NETWORK.

PMID- 1372980
TI  - Serotype conversion in Vibrio cholerae O1.
AB  - Vibrio cholerae O1 exists as two major serotypes, Inaba and Ogawa, which are
      associated with the O antigen of the lipopolysaccharide and are capable of
      unequal reciprocal interconversion. The 20-kilobase rfb regions encoding O
      antigen biosynthesis in strains 569B (Inaba) and O17 (Ogawa) have been cloned in
      Escherichia coli K-12 and the nucleotide sequences have been determined. Besides
      several base substitutions and a small deletion in the 569B sequence relative to
      O17, there is a single nucleotide change resulting in a TGA stop codon within the
      gene for the 32-kDa RfbT protein. We have demonstrated that rfbT is responsible
      for serotype conversion (Inaba to Ogawa). The construction of a specific rfbT
      mutation in the Ogawa strain O17, and the ability of the gene from O17 to
      complement Inaba strains to Ogawa, confirmed rfbT as the gene required for the
      Ogawa serotype. By Southern hybridization and sequencing of PCR products of a
      number of strains, we have shown that the changes observed in one Inaba strain
      (569B) are not conserved in other Inaba strains. This may explain why some Inaba
      strains are able to convert to Ogawa whereas others are not. The protein encoded
      by rfbT has been identified and expressed in E. coli K-12 using a phage T7
      expression system. Amino-terminal analysis of partially purified protein has
      identified the translational start of the protein. Primer extension studies have
      enabled the 5' end of the mRNA to be defined. It exists as a separate transcript
      from the rest of the rfb region, and the distinctive G + C content of rfbT
      suggests that it has been acquired from a non-Vibrio source.

PMID- 1372981
TI  - In vivo T-cell ablation by a holo-immunotoxin directed at human CD3.
AB  - We have evaluated the in vivo efficacy of anti-CD3-CRM9, a holo-immunotoxin
      constructed with a diphtheria toxin binding-site mutant. Eighty percent of
      established human T-cell subcutaneous tumors in nude mice completely regressed
      following intraperitoneal injection of immunotoxin at a dose set at half the
      minimum lethal dose assayed in toxin-sensitive animals. Similar regressions
      produced by a 137Cs source required a dose in excess of 500 cGy. The high degree
      of in vivo T-cell ablation produced by this immunotoxin is apparently due to
      maintenance of the toxin translocation function provided by CRM9 and a necessary
      intracellular routing function supplied by CD3. This immunotoxin may be useful in
      treating conditions caused by pathologic oligoclonal T-cell expansion such as
      graft-versus-host disease, autoimmune diseases, and possibly AIDS.

PMID- 1372982
TI  - Mobilization of dantrolene-sensitive intracellular calcium pools is involved in
      the cytotoxicity induced by quisqualate and N-methyl-D-aspartate but not by 2
      amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate and kainate in cultured
      cerebral cortical neurons.
AB  - By using primary cultures of cerebral cortical neurons, it has been demonstrated
      that the antihyperthermia drug dantrolene protects against cytotoxicity induced
      by the excitatory amino acids quisqualate (QA) and N-methyl-D-aspartate (NMDA),
      whereas no effect was observed on cell damage mediated by kainate (KA) or 2-amino
      3-(3-hydroxy-5-methylisoxazol-4-yl)propionate (AMPA). In parallel it was shown
      that KA and AMPA increased the concentration of intracellular free calcium
      ([Ca2+]i) mainly by influx, whereas the increase in [Ca2+]i stimulated by NMDA
      and QA predominantly was caused by release of Ca2+ from intracellular stores,
      which for NMDA seemed to be mediated at least partly by Ca2+ influx. In
      accordance with the effects on cytotoxicity, dantrolene blocked the increase in
      [Ca2+]i elicited by QA and NMDA leaving the increase induced by KA and AMPA
      unaffected. The finding that 2-amino-3-[3-(carboxymethoxy)-5-methylisoxazol-4
      yl]propionate, which regarding toxicity is a selective KA antagonist, only
      reduced the KA-stimulated increase in [Ca2+]i by 30% may suggest that the
      elevation of [Ca2+]i is not the only element in KA-induced cytotoxicity. On the
      other hand, the present study underlines the importance of Ca2+ for cytotoxicity
      induced by some excitatory amino acids (glutamate, NMDA, and QA) and supports the
      current proposal that multiple mechanisms are operating, even concerning calcium
      homeostasis. Because excitatory amino acid-induced cytotoxicity is thought to be
      involved in neuropathological conditions such as ischemia, it is possible that
      dantrolene might be of therapeutic interest.

PMID- 1372983
TI  - A uridine-rich sequence required for translation of prokaryotic mRNA.
AB  - Binding of 30S ribosomal subunits to mRNA during the initiation of prokaryotic
      translation is known to be influenced by the initiation codon and the Shine
      Dalgarno sequence. Site-directed mutagenesis of rnd, the Escherichia coli gene
      encoding RNase D, has now shown that a U8 sequence upstream of the Shine-Dalgarno
      region is also essential for expression of this mRNA. Alteration of two to five
      uridine residues within this sequence has no effect on mRNA levels but decreases
      RNase D protein and activity by as much as 95%, indicating that the U-rich
      sequence acts as an enhancer of translation. Moreover, mutant transcripts bind to
      30S ribosomes in vitro with lower affinity than their wild-type counterparts,
      suggesting that the role of the U8 sequence is in the initial binding of
      ribosomes to the translation initiation region of the message. These data
      demonstrate that sequences other than those previously recognized can be
      essential for translation initiation.

PMID- 1372984
TI  - What is the optimum size for the genetic alphabet?
AB  - An important question in biology is why the genetic alphabet is made of just two
      base pairs (G.C and A.T). This is particularly interesting because of the recent
      demonstration [Piccirilli, J. A., Krauch, T., Moroney, S. E. & Benner, S. A.
      (1990) Nature (London) 343, 33-37] that the alphabet can in principle be larger.
      It is possible to explain the size of the present genetic alphabet as a frozen
      character state that was an evolutionary optimum in an RNA world when nucleic
      acids functioned both for storing genetic information and for expressing
      information as enzymatically active RNA molecules--i.e., ribozymes. A previous
      model [Szathmary, E. (1991) Proc. R. Soc. London Ser. B 245, 91-99] has described
      the principle of this approach. The present paper confirms and extends these
      results by showing explicitly the ways in which copying fidelity and metabolic
      efficiency change with the size of the genetic alphabet.

PMID- 1372985
TI  - Enhanced expression of the developmentally regulated extracellular matrix
      molecule tenascin following adult brain injury.
AB  - Tenascin is an extracellular matrix molecule synthesized and released by young
      astrocytes during embryonic and early postnatal development of the nervous
      system, and it is concentrated in boundaries around emerging functional neuronal
      units. In the adult nervous system, tenascin can be detected only in very low
      levels. Distinct spatial and temporal distributions of tenascin during
      developmental events suggest a role in the guidance and/or segregation of neurons
      and their processes within incipient functional patterns. We show here, using in
      situ hybridization and immunocytochemistry, that stab wounds of the adult mouse
      cerebellar and cerebral cortices result in an enhanced expression of tenascin in
      a discrete region around the lesion site that is associated with a subset of
      glial fibrillary acidic protein-positive astrocytes. Tenascin up-regulation in
      the lesioned adult brain may be directly involved in failed regeneration or
      indirectly involved through its interactions with other glycoconjugates that
      either inhibit or facilitate neurite growth.

PMID- 1372986
TI  - sar: a genetic mouse model for human sarcosinemia generated by ethylnitrosourea
      mutagenesis.
AB  - A mouse mutant with sarcosinemia was found by screening the progeny of
      ethylnitrosourea-mutagenized mice for aminoacidurias. Paper chromatography,
      column chromatography, and gas chromatography-mass spectrometry identified high
      levels of sarcosine in the urine of the mutant mice. While sarcosine cannot be
      detected in the urine of plasma of normal mice, the urinary sarcosine level of
      102 +/- 58 mmol per g of creatinine in the mutant mice was at the upper range of
      the urinary levels (1.5-4.5 mmol of sarcosine per g of creatinine) observed in
      humans with sarcosinemia. Similarly, the plasma sarcosine level of 785 +/- 153
      mumol/liter in the sarcosinemic mice was at the upper range of the plasma
      sarcosine levels (53-760 mumol/liter) observed in affected humans. Sarcosine
      dehydrogenase [sarcosine:(acceptor) oxidoreductase (demethylating), EC 1.5.99.1]
      activity was deficient in sarcosinemic mice. The sarcosinuria phenotype in these
      mice was inherited as an autosomal recessive trait. This mouse mutant provides a
      useful genetic model for human sarcosinemia and for development of therapeutic
      approaches for genetic disease.

PMID- 1372987
TI  - Infectious Sindbis virus transient expression vectors for studying antigen
      processing and presentation.
AB  - Sindbis virus (SIN) is a small positive-strand enveloped RNA virus that infects a
      broad range of vertebrate and insect cells. A SIN vector (called dsSIN), designed
      for transient expression of heterologous RNAs and proteins, was engineered by
      inserting a second subgenomic mRNA promoter sequence into a nonessential region
      of the SIN genome. By using this vector, dsSIN recombinants have been constructed
      that express either bacterial chloramphenicol acetyltransferase, a truncated form
      of the influenza hemagglutinin (HA), or mini-genes encoding two distinct
      immunodominant cytotoxic T lymphocyte (CTL) HA epitopes. Infection of murine cell
      lines with these recombinants resulted in the expression of approximately 10(6)
      10(7) chloramphenicol acetyltransferase polypeptides per cell and efficient
      sensitization of target cells for lysis by appropriate major histocompatibility
      complex-restricted HA-specific CTL clones in vitro. In addition, priming of an
      influenza-specific T-cell response was observed after immunizing mice with dsSIN
      recombinants expressing either a truncated form of HA or the immunodominant
      influenza CTL epitopes. This SIN expression system allows the generation of high
      titered recombinant virus stocks in a matter of days and should facilitate
      mapping and mutational analysis of class I major histocompatibility complex
      restricted T-cell epitopes expressed via the endogenous pathway of antigen
      processing and presentation.

PMID- 1372988
TI  - Retinoic acid mimics transforming growth factor beta in the regulation of human
      immunodeficiency virus expression in monocytic cells.
AB  - Retinoic acid (RA) exerts potent suppressive and upregulatory effects on human
      immunodeficiency virus (HIV) expression in mononuclear phagocytes, strikingly
      similar to the effects of the cytokine transforming growth factor beta (TGF
      beta). RA significantly inhibited phorbol ester-mediated, but not tumor necrosis
      factor alpha-mediated, induction of HIV transcription in the chronically infected
      promonocytic U1 cell line. RA and TGF-beta also completely suppressed the
      induction of virus production in U1 cells by interleukin 6 alone or in
      combination with glucocorticoids, which predominantly upregulate virus expression
      at the posttranscriptional level. Despite the close parallel to TGF-beta-induced
      effects, no evidence was obtained that RA mediated its effect by inducing
      secretion of active TGF-beta 1, -beta 2, or -beta 3. As with chronically infected
      U1 cells, similar inhibitory effects were also observed in primary monocyte
      derived macrophages previously infected with HIV and then exposed to either RA or
      TGF-beta. In contrast, stimulation of monocyte-derived macrophages or U937 cells
      (the parental cell line of U1) with either RA or TGF-beta prior to in vitro
      infection resulted in the enhancement of virus production. Given the already
      successful use of retinoids in the treatment of several malignancies and the
      present demonstration of their capability of blocking the induction of HIV
      expression in infected mononuclear phagocytes, it would be of interest to pursue
      the potential role of this class of compounds in the development of strategies
      aimed at the pharmacologic regulation of HIV expression.

PMID- 1372989
TI  - Reverse transcription polymerase chain reaction for the rearranged retinoic acid
      receptor alpha clarifies diagnosis and detects minimal residual disease in acute
      promyelocytic leukemia.
AB  - The characteristic t(15;17) of acute promyelocytic leukemia (APL) fuses the
      retinoic acid receptor alpha (RAR-alpha) gene on chromosome 17 to a gene on
      chromosome 15 called PML, a putative transcription factor. This distinct
      translocation results in a fusion mRNA detected by Northern analysis. Two cDNAs
      have been isolated that differ in the extent of 3' PML nucleic acid sequence
      contained. This study describes a reverse transcription polymerase chain reaction
      (RT-PCR) assay for the PML/RAR-alpha fusion transcript, which amplifies PML/RAR
      alpha mRNA from APL cells with either reported breakpoint. DNA sequencing of the
      predominant RT-PCR products from 6 patients showed identical RAR-alpha exonic
      breakpoints and two PML breakpoints. This RT-PCR assay was positive in leukemic
      cells from 30/30 APL patients with the molecular rearrangement confirmed by
      cytogenetics or Northern analysis. In leukemic cells of patients with a
      morphologic diagnosis of APL lacking the t(15;17) by routine cytogenetics, a
      positive RT-PCR assay predicted clinical response to all-trans-retinoic acid (RA)
      therapy. Dilutional studies with leukemic cells that express (NB4) or do not
      express (HL-60) a PML/RAR-alpha fusion mRNA reveal that this RT-PCR assay detects
      the transcript from as little as 50 pg of total RNA. In APL cells from 5/6
      patients treated with RA alone, a complete response by clinical and cytogenetic
      criteria accompanied a persistently positive RT-PCR assay. This preceded relapse
      by 1-6 months. RT-PCR for PML/RAR-alpha mRNA provides a more-sensitive test for
      the t(15;17) than routine cytogenetics or Northern analysis. This molecular
      rearrangement detected by RT-PCR best defines this RA-responsive malignancy. The
      RT-PCR assay for the PML/RAR-alpha transcript yields important diagnostic and
      prognostic information in the management of APL patients.

PMID- 1372990
TI  - A common antiviral cytotoxic T-lymphocyte epitope for diverse major
      histocompatibility complex haplotypes: implications for vaccination.
AB  - Of nine established murine haplotypes, mice of three types (H-2d, H-2u, and H-2q)
      possess major histocompatibility complex class I glycoproteins able to present an
      identical viral peptide for recognition and lysis by virus-specific cytotoxic T
      lymphocytes. Incorporation of this viral epitope into a recombinant vaccinia
      vaccine and administration of a single dose protects mice with these three
      haplotypes from an ordinarily lethal challenge of virus. Hence, a common epitope
      can exist. The sharing of the ability to bind such epitopes among different MHC
      haplotypes underscores the feasibility of developing an effective cytotoxic T
      lymphocyte vaccine for outbred populations like humans.

PMID- 1372991
TI  - Stimulation of protein-tyrosine phosphorylation in rat striatum after lesion of
      dopamine neurons or chronic neuroleptic treatment.
AB  - Even though the short-term actions of dopamine on postsynaptic receptors are well
      characterized, the molecular bases for long-term trophic interactions between
      dopamine neurons and their targets remain unclear. Since protein-tyrosine
      phosphorylation plays a key role in the action of trophic factors, we have
      investigated its possible involvement in the interactions between dopamine
      neurons and their striatal targets. Lesioning rat nigrostriatal dopamine neurons
      by using 6-hydroxydopamine increased the phosphorylation on tyrosine of several
      proteins, including a major 180-kDa protein (pp180) in the ipsilateral striatum.
      Protein-tyrosine kinase activity was also increased in the striatum ipsilateral
      to the lesion, whereas no change in phosphotyrosine phosphatase activity was
      detected. The stimulation of pp180 phosphorylation was observed 1, 2, and 8 weeks
      after 6-hydroxydopamine lesion, was selective for the destruction of dopamine
      neurons, and was mimicked by chronic blockade of dopamine receptors with
      neuroleptics. Additional lesion experiments and subcellular fractionation showed
      that pp180 is located in neuronal postsynaptic densities, suggesting that pp180
      is a postsynaptic component of corticostriatal synapses. Our results indicate
      that lesion of specific afferent fibers can activate tyrosine phosphorylation in
      central neurons and suggest that tyrosine phosphorylation is involved in the long
      term consequences of dopamine deficiency and may play a role in synaptic
      plasticity.

PMID- 1372992
TI  - Isolation of a candidate human hematopoietic stem-cell population.
AB  - We have identified a rare (0.05-0.1%) subset of human fetal bone marrow cells
      that contains multipotent hematopoietic precursors. The population of human
      precursor cells that express Thy-1 and CD34 but no known lineage markers is
      enriched for clonogenic activity that establishes long-term, multilineage
      (myelomonocytic and B lymphoid) cultures on mouse marrow stromal lines. Further,
      the Thy-1+CD34+ subset that takes up little of the fluorescent mitochondrial dye
      rhodamine 123 contains virtually all the cells that establish long-term cultures.
      In human fetal thymus transplanted into SCID (severe combined immunodeficiency)
      mice, Thy-1+CD34+ fetal bone marrow cells differentiate into T lymphocytes. In
      two of nine cases, allogeneic Thy-1+CD34+ cells could engraft intact human fetal
      bone marrow grown in SCID mice, resulting in donor-derived myeloid and B cells.
      By extrapolation, the rare human Thy-1+Lin-CD34+ cell population contains
      pluripotent hematopoietic progenitors; we propose that it is highly enriched for
      candidate hematopoietic stem cells.

PMID- 1372993
TI  - CDK2 encodes a 33-kDa cyclin A-associated protein kinase and is expressed before
      CDC2 in the cell cycle.
AB  - Critical cell cycle transitions are controlled by the coordinate actions of the
      p34cdc2 protein kinase and its regulatory subunits, cyclins. Recently we
      identified another human p34 homolog, cyclin-dependent kinase 2 (CDK2) by
      complementation of a cdc28-4 mutation in Saccharomyces cerevisiae using a lambda
      YES human cDNA expression library. CDK2 is 66% identical to CDC2Hs and 89%
      identical to the Xenopus Eg1 gene, forming a distinct subfamily of CDC2-related
      protein kinases. We have found that CDK2 encodes a 33-kDa cyclin A-associated
      protein kinase that contains phosphotyrosine, two characteristics it shares with
      CDC2Hs. However, we show that the subunit composition of these two protein kinase
      complexes can vary in different cell types, that they have different in vitro
      substrate preferences, and that CDK2 mRNA is observed much earlier than CDC2Hs
      mRNA when lymphocytes are stimulated to enter the cell cycle. We suggest that
      cells in different developmental or transformed states may have different
      mechanisms of cell cycle regulation.

PMID- 1372994
TI  - p107wee1 is a dual-specificity kinase that phosphorylates p34cdc2 on tyrosine 15.
AB  - p107wee1 is a protein kinase that functions as a dose-dependent inhibitor of
      mitosis through its interactions with p34cdc2 in Schizosaccharomyces pombe. To
      characterize the kinase activity of p107wee1, its carboxyl-terminal catalytic
      domain was purified to homogeneity from overproducing insect cells. The apparent
      molecular mass of the purified protein (p37wee1KD) was determined to be
      approximately 37 kDa by gel filtration, consistent with it being a monomer.
      Serine and tyrosine kinase activities cofiltered with p37wee1KD, demonstrating
      that p107wee1 is a dual-specificity kinase. In vitro, p107wee1 phosphorylated
      p34cdc2 on Tyr-15 only when p34cdc2 was complexed with cyclin. Neither monomeric
      p34cdc2 nor a peptide containing Tyr-15 was able to substitute for the
      p34cdc2/cyclin complex in this assay. Furthermore, the phosphorylation of p34cdc2
      by p107wee1 in vitro inhibited the histone H1 kinase activity of p34cdc2. These
      results indicate that p107wee1 functions as a mitotic inhibitor by directly
      phosphorylating p34cdc2 on Tyr-15 and that the preferred substrate for
      phosphorylation is the p34cdc2/cyclin complex.

PMID- 1372995
TI  - Both p21ras and pp60v-src are required, but neither alone is sufficient, to
      activate the Raf-1 kinase.
AB  - The raf genes encode a family of cytoplasmic proteins with intrinsic protein
      serine/threonine kinase activity. The c-raf gene is the cellular homolog of v
      raf, the transforming gene of murine sarcoma virus 3611. The constitutive kinase
      activity of the v-Raf protein has been implicated in transformation and
      mitogenesis. The activity of Raf-1, the protein product of the c-raf gene, is
      normally suppressed by a regulatory N-terminal domain. Activation of various
      tyrosine-kinase growth factor receptors results in activation of Raf-1 and its
      hyperphosphorylation. Further, Raf-1 has been shown to act either downstream or
      independently of the p21ras protein, as indicated by experiments involving
      microinjection of anti-Ras antibodies. To investigate the potential role of
      p21ras in the activation of Raf-1 by tyrosine kinases, we have used the
      baculovirus/Sf9 cell system to overproduce various wild-type and mutant forms of
      pp60src, p21ras, and Raf-1 proteins. We show that either pp60v-src or p21c-ras
      can independently activate the autokinase activity of Raf-1, but only to a
      limited extent. Surprisingly, both pp60v-src and p21c-ras are required to fully
      activate Raf-1. Analysis of the Raf-1 autokinase activity in vitro shows that Raf
      1 autophosphorylation sites are distributed equally on serine and threonine
      residues. When Raf-1 is analyzed by immunoblotting, as previously reported for
      mammalian cell experiments, a marked increase in the apparent molecular weight of
      Raf-1 is seen only when it is coexpressed with both pp60v-src and p21ras.

PMID- 1372996
TI  - Molecular associations between the T-lymphocyte antigen receptor complex and the
      surface antigens CD2, CD4, or CD8 and CD5.
AB  - The T-cell antigen receptor (TCR) complex is the key structure involved in signal
      transduction in T cells. To analyze associations between the TCR complex and
      other molecules, immunoprecipitations were carried out, followed by
      phosphorylation of molecules in vitro by tyrosine kinases associated with the
      precipitated molecules. This provided a sensitive assay for molecular complexes,
      and associations were demonstrated between the TCR complex and the surface
      antigens CD2, CD4, or CD8 and CD5 in normal rat T cells. The complexes were
      readily seen in immunoprecipitates from Brij 96 but not Nonidet P-40 detergent
      extracts. The multimolecular complexes are associated with the internal tyrosine
      kinases p56lck and p59fyn. The presence of p56lck associated with CD4 or CD8 was
      also examined in early thymocytes, natural killer cells, and macrophages. The
      kinase was present in all cases except that of normal macrophages.

PMID- 1372997
TI  - Coordinated synthesis and degradation of cdc2 in the mammalian cell cycle.
AB  - The product of the cdc2 gene (cdc2 or p34cdc2), the catalytic subunit of M phase
      promoting factor (MPF), is held at a constant steady-state level throughout the
      cell cycle. In this report, we show that the constant concentration is maintained
      by a coordinated regulation of protein synthesis and degradation. At the end of
      each mitosis, cdc2 transcription is shut off, and the mRNA is rapidly degraded. A
      12-fold activation of cdc2 gene transcription occurs every round of the cell
      cycle at the G1/S transition, in a growth factor-dependent manner. The increase
      in mRNA correlates with the accumulation of newly synthesized cdc2 during S and
      G2 phases. At the onset of mitosis, the translation of cdc2 mRNA is shut off.
      During G1 phase, the cdc2 protein has a relatively long half-life of 18 hr, so
      cdc2 made in the previous cell cycle is maintained. Once synthesis is activated
      at G1/S, a concurrent mechanism of degradation is activated, and the protein half
      life is reduced to 7.5 hr. By the end of interphase, new cdc2 accounts for 75-85%
      of the total cdc2 pool. In addition, we show that greater than 75% of the new
      cdc2 complexes with cyclin, suggesting that a majority of the new cdc2 functions
      as MPF.

PMID- 1372998
TI  - Angiogenesis in skeletal and cardiac muscle.

PMID- 1372999
TI  - Stimulatory effect of vasoactive intestinal peptide (VIP) on cyclic AMP
      production in rat peritoneal macrophages.
AB  - Vasoactive intestinal peptide (VIP) stimulated cyclic AMP production in rat
      peritoneal macrophages. The stimulatory effect of VIP was dependent on time,
      temperature and cell concentration, and was potentiated by the phosphodiesterase
      inhibitor 3-isobutyl-1-methylxanthine (IBMX). At 15 degrees C, the response
      occurred in the 0.1-1000 nM range of VIP concentrations. Half maximal stimulation
      of cellular cyclic AMP (ED50) was obtained at 1.2 +/- 0.5 nM VIP, and maximal
      stimulation (about 3-fold basal level) was obtained between 100-1000 nM. The
      cyclic AMP system of rat peritoneal macrophages showed a high specificity for
      VIP. The order of potency observed in inducing cyclic AMP production was VIP
      greater than rGRF greater than hGRF greater than PHI greater than secretin.
      Glucagon, insulin, pancreastatin and octapeptide of cholecystokinin did not
      modify cyclic AMP levels at concentrations as high as 1 microM. The beta
      adrenergic agonist isoproterenol increased the cyclic AMP production and show
      additive effect with VIP. Somatostatin inhibits the accumulation of cyclic AMP in
      the presence of both vasoactive intestinal peptide and isoproterenol. The finding
      of a VIP-stimulated cyclic AMP system in rat peritoneal macrophages, together
      with the previous characterization of high-affinity receptors for VIP in the same
      cell preparation, strongly suggest that VIP may be involved in the regulation of
      macrophage function.

PMID- 1373000
TI  - A supportive role of neural cell adhesion molecule (NCAM) in adhesion between
      leukaemic blasts and cytotoxic lymphocytes.
AB  - The expression and function of neural cell adhesion molecule (NCAM, CD56, Leu19)
      on leukaemic blasts was investigated. The expression of NCAM was frequent (64%)
      in 14 studied cases of acute myeloid leukaemia (AML) but not in chronic
      lymphocytic leukaemia (CLL: 1/3 cases positive) or immunocytoma (IC: no
      positivity). No correlation with the expression of other AM (intercellular
      adhesion molecule-1 (ICAM-1), leucocyte function antigen-1 (LFA-1). VLA beta
      chain) or with AML type, according to FAB classification, was observed. Blocking
      of NCAM with anti-Leu 19 MoAb on AML targets resulted in a significant decrease
      of their susceptibility to LAK killing and in inhibition of conjugate formation.
      In the case of B prolymphocytic leukaemia (B-PLL) which did not express ICAM-1 or
      LFA-1 but was NCAM+, a complete resistance to LAK activity and lack of conjugate
      formation was observed. Blocking of NCAM on LAK effectors did not decrease their
      cytotoxic activity. Our results suggest that NCAM, in the presence of other AM,
      may have a supportive role in adhesion of leukaemic targets to LAK effectors.

PMID- 1373001
TI  - Preferential interaction of the CD4+29+/45RA-subset of human CD4+ T lymphocytes
      with an antibody against the cell-membrane ganglioside GD3.
AB  - This study shows that the two major subpopulations of CD4+ T lymphocytes defined
      on the basis of differential expression of the CD29 and CD45RA antigens, show
      significant differences in reactivity with a monoclonal antibody against the GD3
      ganglioside. Double staining studies showed that the GD3 ganglioside is
      predominantly expressed on cells from the CD4+29+/45RA subsets. The preferential
      interaction of the CD4+29+/45RA cell subset with the anti-GD3 MoAb was further
      confirmed by the proliferative and calcium-flux studies. Accordingly, the
      reciprocal, CD4+(29-)/45RA+ subset was unable to proliferate in response to the
      anti-GD3 MoAb alone. Although it did show a significant mobilization of calcium
      ions and proliferation to IL-2 when stimulated with the anti-GD3 MoAb, these
      response were much less pronounced than the responses of the CD4+29+/45RA-
      subset. Finally, when two T-cell stimulating monokines, IL-1 and IL-6, were
      tested for the ability to modulate the anti-GD3 mediated proliferation, only the
      former, but not the latter was able to enhance the proliferation. Although the
      natural ligand for the GD3 ganglioside remains unknown, the data presented here
      provide further evidence in support of the notion that the T-cell surface
      molecules different from the T-cell receptor MHC-antigen complex may contribute
      to the preferential activation of one of the CD4+ T lymphocyte subsets.

PMID- 1373002
TI  - Multiparametric flow cytometric analysis of the kinetics of surface molecule
      expression after polyclonal activation of human peripheral blood T lymphocytes.
AB  - In this report we have analysed the kinetics of modulation of human peripheral
      blood T lymphocyte membrane molecules upon activation with optimal amounts of
      phytohaemagglutinin (PHA) and concanavalin A (ConA). The following activation
      related and differentiation/adhesion molecules were selectively and concomitantly
      investigated on CD4+ and CD8+ subsets by dual colour flow cytometry: CD69, CD25
      and CD71; CD2, CD45RA and L-selectin. Cultures were assayed after 24, 48, 72, 120
      and 168 h of incubation with PHA and ConA. This approach allowed a comprehensive
      evaluation of membrane phenomena occurring during activation of normal resting
      human T lymphocytes. Data show that the kinetics of expression of these molecules
      follows a precise and consistent time-course with no major differences between
      CD4 and CD8 subsets. CD69 expression peaked at 24 h, whereas CD25 and CD71
      expression peaked at 48/72 h with some differences between PHA and ConA
      activation. L-selectin expression started an evident decrease in step with
      culture time whose magnitude was dependent on the lectin used, being higher with
      PHA than with ConA. Conversely, the expression of CD45RA remained stable for 72 h
      and then briskly decreased with no major differences between PHA and ConA
      activation. CD2 molecules increased with time in number and density, although the
      percentage of positive cells remained essentially constant (greater than 85%).
      After 48/72 h of stimulation about 10% of cells co-expressed CD4 and CD8
      molecules. To ascertain whether the phenomenon was restricted to cells in a
      particular activation state, the phenotype of cells in the diverse phases of the
      cell cycle was established. Results obtained show that only actively
      proliferating cells, that is cells in S and G2-M phases, co-expressed the two
      molecules, suggesting that such a phenomenon reflects a momentary dysregulation
      of the normal sequence of gene expression. The present data are also discussed in
      the light of the dynamic role of T lymphocyte activation and adhesion molecules
      in regulating cell-cell interactions, tissue localization and eventual
      immunological function.

PMID- 1373003
TI  - Cancer cell invasion and metastasis.
AB  - The most life-threatening aspect of cancer is the undetected spread of tumor
      cells throughout the body. Improved understanding of how these cells invade
      tissues is leading to new treatments.

PMID- 1373004
TI  - Chemotherapeutic strategies in metastatic colorectal cancer: an overview of
      current clinical trials.
AB  - 5-Fluorouracil (5-FU) is still the mainstay of chemotherapy in patients with
      metastatic colorectal cancer. A prolonged infusion of 5-FU is more active than
      any other schedule of 5-FU used to date. Cisplatin does not improve treatment
      results compared with 5-FU alone and is not recommended outside clinical trials.
      Biomodulation of 5-FU is a major step forward in the treatment of colorectal
      cancer patients and as the standard chemotherapy for advanced colorectal cancer.
      Two schedules of folinic acid daily for 5-day (low and high doses) and weekly
      high dose in combination with daily or weekly 5-FU are the most widely used
      schedules. Although the response rates to either schedule are comparable, the
      profile of toxicity is different, being stomatitis for the daily schedule and
      diarrhea for the weekly schedule as the dose-limiting toxicity. Modulation of 5
      FU by methotrexate is time dependent. An interval of 24 hours between
      methotrexate and 5-FU is necessary for effective modulation. Other modulators,
      like interferon and N-phosphonoactyl-L-aspartate (PALA), are promising treatment
      options currently under investigation in randomized trials. The data from phase
      II and III trials using modulation of 5-FU by folinic acid, PALA, or
      methotrexate, or using continuous infusion 5-FU indicate that all of these
      strategies are active. Randomized trials are currently underway to further
      investigate these therapeutic approaches and whether a specific modulation offers
      more therapeutic advantages.

PMID- 1373005
TI  - Principles in the biomodulation of cytotoxic drugs by interferons.
AB  - The interferons (IFNs) were identified as novel, endogenous antiviral agents in
      1957. Shortly thereafter, antiproliferative and immunostimulatory activities were
      identified for these compounds. Based on these observations, partially purified
      IFNs entered clinical trials in the 1970s and recombinant IFNs in 1980. IFNs have
      demonstrated important clinical activity in hairy cell leukemia, melanoma, renal
      cell carcinoma, and Kaposi's sarcoma as monotherapy. Shortly after their
      introduction into clinical trials, however, preclinical studies demonstrated
      synergistic interactions between IFNs and cytotoxic drugs. Numerous preclinical
      trials have demonstrated a broad spectrum of interactions between IFNs and at
      least 20 cytotoxic agents both in vitro and in vivo. Early clinical trials
      suggest a benefit to combinations of fluorouracil and recombinant interferon alfa
      in refractory gastrointestinal malignancies. Combinations of IFNs and cytotoxic
      agents deserve further investigations; however, different principles apply for
      combining IFNs with cytotoxic drugs than for the design of combination
      chemotherapy regimens.

PMID- 1373006
TI  - Synergistic antitumor interactions between newly synthesized ruthenium complexes
      and cytokines in human colon carcinoma cell lines.
AB  - The purpose of these studies was to assess the antiproliferative properties of
      newly synthesized, heterocyclic ruthenium complexes alone and in combination with
      cytokines (tumor necrosis factor-alpha, interferon alfa, beta, and gamma) against
      various human colon carcinoma cell lines. To determine whether any of these
      ruthenium compounds possesses antitumor activity and reveals synergistic
      interaction with cytokines six new ruthenium complexes were studied. All six
      compounds exerted dose-dependent antitumor effects in all colon cancer cell lines
      tested. The most effective compounds were trans-indazolium[tetrachloro(2H
      indazole)ruthenate (III, N1)] and trans-indazolium[tetrachlorobis(1 H
      indazole)ruthenate (III, N2)]. Interferon alfa, beta, and gamma as well as tumor
      necrosis factor-alpha exerted only minimal antiproliferative effects in colon
      carcinoma cell lines. The data were further analyzed to determine whether
      preincubation with cytokines altered sensitivity of the cells to synergistically
      potentiating growth-inhibitory effects. Although simultaneous incubation of
      ruthenium complexes and interferon did not result in synergistic or additive
      interactions, 24-hour preincubation with interferon alfa, beta, and gamma
      significantly enhanced antitumor activity. We conclude from these data that two
      of six newly synthesized ruthenium complexes possess antiproliferative activity
      against a panel of human colon carcinoma cell lines. Moreover, biological
      modulation with interferon using 24-hour preincubation resulted in synergistic
      interactions. We are planning a phase I trial, since antitumor activity of these
      ruthenium compounds has been demonstrated in vitro and in vivo, and toxicity as
      well as stability data are now available.

PMID- 1373008
TI  - Capillary and venule proliferation in the healing process of Dacron venous grafts
      in rats.
AB  - A woven, noncrimped graft (made of Dacron and coated with an elastomer) that was
      1.5 mm in diameter and 15 mm long was capable of replacing the vena cava in rats.
      The elastomer mixture consisting mainly of silicone rubber was necessary to bond
      the woven Dacron fibrils of the woven graft to prevent fraying at the anastomoses
      and bleeding through the interstices of the lightly woven, fairly high porosity
      (500) conduit. Sequential histologic studies showed that patency was associated
      with the ingrowth of small venules and the spreading of endothelial cells from
      each anastomosis toward the center. Small venules appeared in loose connective
      tissue, forming a pseudointima 12 days after grafting. This process occurred in
      the midportion of the graft before pannus endothelial growth covered the
      endothelial surface. Various thicknesses of the external polymer coat were
      studied for their influence on healing. None of the grafts developed a thrombus
      in these latter studies, and regardless of the thickness of the external
      elastomer, endothelial resurfacing was complete at 30 days. However, the graft
      with the thinnest external elastomer coating had the best-formed vasa vasorum,
      and the intima at both the anastomoses and midportions of the graft was
      significantly thinner than intima found in grafts of other composition. We
      conclude that this woven Dacron polygraft provides a surface resistant to early
      thrombosis; that healing occurs mainly by pannus ingrowth, but external and
      interstitial factors are also important; and that properties inherent in the
      polygraft wall determine the size of the residual lumen.

PMID- 1373007
TI  - Hypertonic solutions in the treatment of hypovolemic shock: a prospective,
      randomized study in patients admitted to the emergency room.
AB  - BACKGROUND: The infusion of small volumes of hypertonic saline solution or
      hypertonic saline plus dextran 70 is remarkably effective in restoring adequate
      hemodynamic conditions after hypovolemic shock. This prospective double-blind
      study compares the immediate hemodynamic effects of a bolus infusion of 7.5% NaCl
      or 7.5% NaCl plus 6% dextran 70 (both 2400 mOsm/L) in severe hypovolemia.
      METHODS: One hundred five adult patients admitted in hypovolemic shock (systolic
      blood pressure less than 80 mm Hg) were revived on arrival to the emergency room
      and administration of a 250 ml intravenous bolus of hypertonic saline solution (n
      = 35), hypertonic saline plus dextran (n = 35), or isotonic saline solution (n =
      35). This infusion was immediately followed by standard crystalloid and blood
      replacement until systolic pressure reached 100 mm Hg. Mean arterial pressure
      (MAP) was measured every 5 minutes, and all intravenous infusions were
      registered. Plasma volume expansion was calculated from plasma protein
      concentration measurements. Patients were followed up throughout their hospital
      course, and results of treatment were recorded. RESULTS: At the end of the
      infusion period, and 5 and 10 minutes after infusion, MAP was significantly
      higher in patients receiving either hypertonic solution, compared with the group
      receiving isotonic solution. All groups showed similar trends toward restoration
      of hemodynamic parameters thereafter. The calculated plasma volume expansion,
      immediately after the bolus infusion, was significantly higher (24.1% +/- 1.8%
      and 24.9% +/- 1.1%) in the hypertonic groups, compared with isotonic groups (7.9%
      +/- 1.3%). Significantly greater volumes of fluids were required to restore
      systolic pressure in the patients receiving isotonic saline solution than in the
      groups receiving hypertonic solution. There were no significant differences
      between the groups receiving hypertonic solutions. The incidence of complications
      was low, and the mortality rate was similar in all groups. CONCLUSIONS: Infusion
      of 250 ml hypertonic saline solution in patients with severe hypovolemia was not
      related to any complications, nor did it affect mortality rates; it improved MAP
      significantly, acutely expanded plasma volume by 24%, and reduced significantly
      the volumes of crystalloids and blood required in their resuscitation.

PMID- 1373009
TI  - [Volume therapy in traumatology].
AB  - Circulatory failure is the most dominating problem in the multitraumatized
      patient in hospital. This article describes the most important pathophysiological
      events from a compensated stage to the final irreversible stage. The practical
      consequences for both the doctor and the patient are the amount of bleeding and
      the duration of the stage of shock. When there are technical problems with venous
      access we recommend surgical cut-down of peripheral veins. The article also
      describes the principal quality of the most commonly used volume substitutes.
      Finally, the author discusses the use of sodium bicarbonate in the event of
      lactacidosis.

PMID- 1373010
TI  - Immunochemical properties of Naja naja atra (Taiwan cobra) phospholipase A2 using
      polyclonal and monoclonal antibodies.
AB  - The immuno-chemical properties of Naja naja atra phospholipase A2 (NNA-PLA2) were
      studied by using the chemically modified PLA2 derivatives and the PLA2 homologues
      toward anti-NNA-PLA2 polyclonal and monoclonal antibodies. Anti-NNA-PLA2
      polyclonal antibodies inhibited the enzymatic activity of NNA-PLA2 and Hemachatus
      haemachatus DE-I by 87% and 68%, respectively. However, the enzymatic activities
      of Naja nigricollis CMS-9 and notexin were not significantly affected by the
      polyclonal antibodies. Competitive enzyme immunoassay revealed that the affinity
      of NNA-PLA2 for polyclonal antibodies was 330-fold higher than that of Hemachatus
      haemachatus DE-I. Naja nigricollis CMS-9 and notexin failed to inhibit the
      binding of NNA-PLA2 to polyclonal antibodies. This implies that the epitope(s) of
      NNA-PLA2 might comprise some substituted residues in the sequence of PLA2
      homologues. Three monoclonal antibodies against NNA-PLA2 were prepared by a
      hybridoma technique. Two of these monoclonal antibodies inhibited the enzymatic
      activity of NNA-PLA2, but the other did not. Removal of the N-terminal
      octapeptide affected the epitope interacting with these monoclonal antibodies.
      Selective modification of tyrosine residues at positions 3 and 63 or lysine
      residues at positions 6 and 65 induced a substantial reduction in affinity of NNA
      PLA2 for polyclonal and monoclonal antibodies. The three monoclonal antibodies
      failed to recognize PLA2 homologues. The comparison of the sequence of NNA-PLA2
      to those of PLA2 homologues showed that most of the amino acid substitutions of
      PLA2 homologues occur in the spatially nearby region of the N-terminal region and
      residues at positions 63 and 65.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373011
TI  - Unusual extraskeletal myxoid chondrosarcoma.
AB  - We describe an unusual soft tissue tumor occurring within the rectus femoris
      muscle of a 64-year-old woman. The site, size, macroscopic, and histological
      appearances were all consistent with an extraskeletal myxoid chondrosarcoma.
      However, the present case differs significantly from previous reports of this
      uncommon tumor in that electron microscopy did not show any evidence of
      chondroblastic differentiation. Furthermore, the cells failed to stain for
      vimentin while labeling intensely for neuron-specific enolase, contained large
      numbers of cytolysosomes having a multivesicular appearance, and focally produced
      an external lamina. Based on the typical histological appearances we conclude
      that this is an unusual variant of extraskeletal myxoid chondrosarcoma in which
      there is evidence of nerve sheath differentiation.

PMID- 1373012
TI  - Merkel cell carcinoma with pagetoid spread.
AB  - A case of Merkel cell carcinoma showing epidermotropism is presented. The
      neoplastic cells displayed dotlike immunoreactivity for cytokeratins and strong
      immunoreactivity for neuron-specific enolase. Although no neuroendocrine granules
      were found, characteristic paranuclear fibrous bodies were present.

PMID- 1373014
TI  - Transurethral resection of prostate immediately after renal transplantation.
AB  - The subject of transurethral resection of the prostate (TURP) after renal
      transplantation has not been evaluated in the urologic literature. We
      retrospectively compared the outcome of renal transplantation in 8 patients who
      underwent transurethral resection of the prostate within ten days of renal
      transplantation with 8 patients who did not undergo prostate surgery. Patients
      were computer-matched for seven parameters. There was no statistically
      significant difference in patient survival (6 vs 7) and graft survival (56% vs
      88%) between the two groups. However, there was a 25 percent incidence of major
      perioperative complications (including one mortality) in the TURP group directly
      attributable to the procedure. Transurethral resection of the prostate can be
      safely performed immediately after renal transplantation only if urine is
      sterile, antibiotics and steroids are carefully administered perioperatively, low
      gravity irrigation is used, and hemostasis is meticulous.

PMID- 1373013
TI  - Balloon dilatation of prostate: keys to sustained favorable results.
AB  - Seventy-seven patients with small prostates (less than 40 g) and significant
      obstructive symptomatology were treated using balloon dilatation of the prostate
      (BDP) with a sized-to-fit intra-prostatic balloon. Eighty-seven percent of the
      patients experienced a 50 percent or greater decrease in symptom score at longest
      follow-up (12.0 months, average: 3-24 months, range). Forty-nine percent of the
      patients had a 50 percent or greater improvement in peak uroflow. An anterior
      commissurotomy through the fibromuscular stroma was consistently found and is the
      hallmark of a technical and therapeutic success. No cases of incontinence,
      retrograde ejaculation, or impotence developed. When properly performed, BDP has
      a place in the spectrum of BPH treatment alternatives.

PMID- 1373015
TI  - Detection of residual prostate cancer after radiotherapy by sonographically
      guided needle biopsy.
AB  - Detection of persistent or recurrent prostate cancer by digital rectal
      examination (DRE) after definitive radiotherapy is difficult. With the
      availability of transrectal ultrasonography (TRUS), the detection of prostate
      cancer has improved substantially. Since 1987 we have used TRUS to evaluate the
      prostate after definitive radiotherapy. A hypoechoic lesion suggestive of cancer
      was identified in 45 of 56 patients (80%) studied. Sonographically directed
      transrectal needle biopsies were performed in 27 of these (60%), and 16 (59%)
      were positive for cancer. The presence of a palpable nodule suggestive of cancer
      (present in 7 patients) was not predictive of a positive biopsy specimen. In 14
      patients ultrasound-guided and digitally-guided biopsies were performed at the
      same time; 8 (57%) of the ultrasound-guided biopsy specimens were positive
      compared with only 4 (29%) of the digitally-guided biopsy specimens. In all 7
      patients with an elevated serum level of prostate-specific antigen (PSA) an
      ultrasound-guided biopsy result was positive. Random biopsies of sonographically
      normal (isoechoic) areas of the prostate were performed in 8 patients, but only 2
      specimens (25%) were positive for cancer. Ultrasound-guided transrectal biopsy of
      hypoechoic lesions was a safe and effective technique for identifying residual
      cancer in the irradiated prostate, regardless of the palpable findings. In the
      presence of an elevated PSA level, such biopsies invariably identified residual
      cancer. The use of TRUS, ultrasound-guided biopsy, and the measurement of PSA, in
      addition to DRE, may aid in the detection of residual cancer after definitive
      radiotherapy.

PMID- 1373016
TI  - Murine cross-reactive T-cell epitopes of Neisseria meningitidis outer membrane
      proteins.
AB  - Five non-covalent vaccines of outer membrane proteins (OMPs) complexed to
      capsular polysaccharide were prepared from Neisseria meningitidis serogroup B
      strains. Each vaccine contained distinct serotype (class 2/3) and subtype (class
      1) OMPs. The cross-reactivity of the T-cell response to the meningococcal vaccine
      associated proteins was examined in an in vitro T-cell proliferative assay,
      following antigenic priming of mice with one of these vaccines (MB6:P1.6) or with
      its purified class 1 (subtype P1.6) and class 2 (serotype 6) proteins. Cross
      reactive T-cell epitopes were found in all five vaccine preparations on both the
      class 1 and class 2/3 OMPs. Priming of mice with the subtype P1.6 N-terminal
      peptide led to a significant but small increase in T-cell proliferation with the
      MB6:P1.6 vaccine.

PMID- 1373017
TI  - A comparative study of histological and immunohistochemical methods for
      neurofibrillary tangles and senile plaques in Alzheimer's disease.
AB  - Several studies have demonstrated that the accurate visualization and
      quantification of pathological lesions in neurodegenerative disorders depend on
      the reliability of staining methods. In an attempt to gain a better assessment of
      the density and distribution of the neuropathological markers of Alzheimer's
      disease, we compared the staining efficiency of a modified thioflavine S protocol
      for neurofibrillary tangles (NFT) and senile plaques (SP) to different argentic
      impregnation techniques (Bielchowsky, Gallyas, Globus, Campbell-Switzer-Martin)
      and to immunohistochemical stainings obtained with two different antibodies
      against the amyloid beta protein A4 and the microtubule-associated tau protein.
      The modified thioflavine S technique (MTST) detects up to 60% more SP and up to
      50% more NFT than the Bielschowsky and Globus methods, respectively. The results
      obtained with the specific antibodies are comparable to those obtained with the
      MTST, but these immunotechniques are more expensive and time consuming for
      routine neuropathological evaluation, and the appropriate antibodies are not
      always commercially available. Furthermore, the morphological appearance of NFT
      and SP with MTST is greatly improved when compared to the classical thioflavine S
      and the increased signal-to-noise ratio between specifically stained structures
      and background permits an accurate semi-automatic quantification.

PMID- 1373019
TI  - Autopsy findings in two siblings with infantile Refsum disease.
AB  - Recognition of adrenal atrophy during a review of autopsy findings in two sisters
      who died at 8 months and 3 1/2 years prompted estimation of very long chain fatty
      acids, phytanic acid and pristanic acid on wet liver fixed in formalin for 12
      years. These were shown to be markedly increased and defects in multiple
      peroxisomal functions and decrease in particulate catalase were shown in cultured
      fibroblasts, confirming an abnormality of peroxisomal biogenesis. The patients
      had presented with failure to thrive, recurrent diarrhoea and vomiting, poor
      mental development, retinal pigmentation, blindness and in the older patient
      deafness, with only mild dysmorphic features. Autopsy in the older patient showed
      adrenal atrophy, cirrhosis, and foamy histiocytes in multiple organs. The brain
      showed no demyelination, little cytoarchitectural abnormality, occasional
      perivascular histiocytes in the grey matter and meninges and prominent Purkinje
      cells in the molecular layer of the cerebellum. In the younger patient the
      changes were very subtle in spite of the marked clinical similarity. Despite the
      young age at death the clinicopathological features are most suggestive of
      infantile Refsum disease. In many situations anatomical pathology can be very
      useful in the recognition and study of peroxisomal disorders.

PMID- 1373018
TI  - Specific monoclonal antibodies against normal microtubule-associated protein-2
      (MAP2) epitopes present in Alzheimer pathological structures do not recognize
      paired helical filaments.
AB  - We have developed monoclonal antibodies that detect normal microtubule-associated
      protein-2 (MAP2) epitopes in routinely fixed, paraffin-embedded tissue. The
      somatodendritic distribution of MAP2 in bovine and human nervous tissue was
      confirmed with several of these antibodies. Furthermore, some of these antibodies
      immunohistochemically labeled certain pathological structures in Alzheimer brain,
      especially neurites in senile plaques. Electron microscopic observations,
      however, indicate that these MAP2 epitopes are not located in the Alzheimer
      paired helical filaments themselves, but in amorphous granular structures
      coexistent with them. While the pathological nature of these structures is
      undetermined, they may represent artefactual modifications of normal cytoskeletal
      components.

PMID- 1373020
TI  - Directional and compartmentalised drainage of interstitial fluid and
      cerebrospinal fluid from the rat brain.
AB  - Pathways for drainage of interstitial fluid and cerebrospinal fluid from the rat
      brain were investigated by the injection of 2-5 microliters Indian ink into
      cerebral white and grey matter and into the subarachnoid space over the vertex of
      the left frontal lobe. Animals were killed by formalin or glutaraldehyde
      perfusion 5 min-2 years after injection, and the distribution of ink over the
      surface of the brain, in 2-mm slices of brain cleared in cedar wood oil, in
      paraffin sections and by electron microscopy was documented. These investigations
      showed that carbon particles were distributed diffusely through the interstitial
      spaces of the white matter whereas they spread selectively along perivascular
      spaces in the grey matter outlining both arteries and veins and extending to
      surround capillaries within 1 h. Carbon particles were rapidly ingested by
      perivascular cells and, to some extent, by meningeal cells surrounding the larger
      vessels. Very little movement of carbon-labelled perivascular cells and
      perivascular macrophages was seen after 2 years. Carbon particles entering the
      subarachnoid space over the vertex of the cerebral hemispheres drained along
      selected paravascular and subfrontal pathways in the subarachnoid space to the
      cribriform plate and thence into nasal lymphatics and cervical lymph nodes. These
      studies demonstrate the diffuse spread of fluidborne tracers through cerebral
      white matter in the rat, the perivascular spread of tracer in grey matter and the
      compartmentalised directional flow or tracer through the subarachnoid space to
      the cribriform plate and nasal lymphatics. Furthermore, particulate matter
      selectively injected into perivascular spaces in rat grey matter is rapidly and
      efficiently ingested by perivascular cells.

PMID- 1373021
TI  - SP-40,40 is a constituent of Alzheimer's amyloid.
AB  - Cerebrospinal fluid (CSF), serum and seminal plasma contain a small amount of SP
      40,40, a modulatory protein of the human complement system. The SP-40,40 in each
      body fluid was different in molecular size on SDS-PAGE, and glioblastoma cells,
      hepatoma cells and testicular tumor cells produced SP-40,40, while neuroblastoma
      cells did not. Therefore, it was estimated that CSF SP-40,40 originated in glia
      cells, serum SP-40,40 in liver cells and seminal plasma SP-40,40 in testicular
      cells. SP-40,40 concentrations in CSF of the patients with Alzheimer's disease
      and the patients with cerebral tumor were higher than those of normal donors.
      beta-Amyloid deposits in the brains of the patients with Alzheimer's disease were
      stained with an anti-SP-40,40 monoclonal antibody (mAb) but not with an anti-S
      protein mAb, while cellular processes around beta-amyloid were stained with an
      anti-S-protein mAb but not with an anti-SP-40,40 mAb. Therefore, beta-amyloid
      contained SP-40,40 in a form different from that in the soluble membrane attack
      complex (SMAC, SC5b-9) of the complement, which contains S-protein as well as SP
      40,40.

PMID- 1373022
TI  - Selective loss of nigral neurons in Alzheimer's disease: a morphometric study.
AB  - Loss of neurons from the substantia nigra (SN), which is sometimes observed in
      Alzheimer's disease (AD), was quantitatively analyzed in 10 cases of presenile AD
      and 19 age-matched controls. On sections from the upper and lower portions of the
      SN, the pigmented zone (zona compacta) and the non-pigmented zone (zona
      reticulata) were delineated, and these zones were partitioned into quarters:
      medial, mid-medial, mid-lateral and lateral. This approach clarified
      topographical preference of neuronal depletion in the SN of AD; namely (1)
      pigmented neurons were more severely affected than non-pigmented neurons, (2)
      neuronal depletion was more marked in the lower SN (-38%, P less than 0.001),
      where the pigmented neurons in the medial quarter were most severely affected (
      51%, P less than 0.001), (3) in the upper SN (neuronal loss: -21%, P less than
      0.01), the pigmented neurons in the mid-medial quarter were most severely
      affected (-43%, P less than 0.01). These findings suggest that some groups of
      nigral neurons are primarily involved in presenile AD. Gallyas staining after
      bleaching of melanin pigments uncovered a large number of neurofibrillary tangles
      (NFTs) mainly in the pigmented zone, especially in the medial quarter. A large
      number of NFTs, scarse senile plaques, and substantial depletion of neurons form
      an unique combination of Alzheimer pathology in the SN not well recognized so
      far.

PMID- 1373023
TI  - Expression of oligodendroglia and Schwann cell markers in human nervous system
      tumors. An immunomorphological study and western blot analysis.
AB  - Sixty tumors of the central and peripheral nervous system and seven brain
      metastases of extracranial carcinomas were examined using the peroxidase
      antiperoxidase method to study the expression of myelin basic protein (MBP),
      myelin-associated glycoprotein (MAG) and the HNK-1/Leu-7 epitope. The
      immunocytochemical findings were compared with and correlated to Western blot
      results. None of the tumor types, including oligodendrogliomas, neurinomas and
      neurofibromas, expressed MAG and MBP, whereas myelin sheaths and their remnants
      within the tumors yielded specific immunoreactions. In contrast, the HNK-1/Leu-7
      antibodies labelled the majority of the tumors tested including
      oligodendrogliomas and Schwann cell tumors. As demonstrated by Western blot
      experiments the HNK-1/anti-Leu-7 antibodies exhibited positive reactions with
      diverse polypeptides both in tumors and in non-neoplastic brain tissue at
      positions not corresponding to MAG. This suggests that the epitope recognized by
      HNK-1/Leu-7 antibodies is shared by a variety of unrelated proteins in normal and
      neoplastic tissues. Our results strongly indicate the absence of detectable
      amounts of MBP and MAG in oligodendrogliomas and Schwann cell tumors. The
      immunomorphological and immunochemical findings clearly showed the wide
      distribution of the HNK-1 epitope within different tumor types of the central and
      peripheral nervous system. In conclusion, the data demonstrate that specific cell
      markers for human oligodendrogliomas and Schwann cell tumors are still lacking.

PMID- 1373024
TI  - Senile plaques, amyloid beta-protein, and acetylcholinesterase fibres: laminar
      distributions in Alzheimer's disease striate cortex.
AB  - The laminar distributions of senile plaques and amyloid beta-protein (A beta P)
      within the striate cortex of patients with Alzheimer's disease (AD) were studied
      with enhanced Bielschowsky (roughly equivalent to the Campbell technique) and
      immunohistochemical methods. The laminar distribution of acetylcholinesterase
      (AChE) fibres within the striate cortex of both AD patients and control patients
      was studied with an enzyme histochemical method. Quantification of Bielschowsky
      stained plaque numbers along intersect lines drawn parallel to laminar boundaries
      revealed a significant aggregation of plaques at the interface of layers IVc and
      V. Lines drawn through layer VI intersected significantly fewer plaques than
      lines through other laminae. Immunoperoxidase staining for A beta P revealed a
      similar distribution of senile plaques, and addition, prominent, diffuse deposits
      of A beta P within layers I and IVc. AChE fibres were markedly depleted in the
      striate cortex of AD cases. In control cases, AChE fibres were, like A beta P
      immunoreactivity, concentrated within layer I and IVc. The results indicate that
      enhanced silver methods may not reveal the complete distribution of A beta P. The
      codistribution of A beta P-immunoreactive diffuse amyloid deposits and AChE
      fibres to the same cortical laminae is consistent with the possibility that these
      deposits may be formed from degenerating cholinergic elements. The formation of a
      line of senile plaques at the interface of two cortical laminae within the
      striate cortex, in an anatomically analogous situation to a similar line of
      plaques within the dentate gyrus, suggests that formation of well-defined plaques
      may be accelerated by the interaction of specific neuronal systems.

PMID- 1373025
TI  - Midline brain tumors in MSV-SV 40-transgenic mice originate from the pineal
      organ.
AB  - Adult transgenic mice expressing the large T-antigen of the Simian virus 40 (SV
      40) under the control of the Moloney murine sarcoma virus (MSV) enhancer and the
      SV 40 promoter develop inheritable uniform midline brain neoplasms showing
      features of primitive neuroectodermal tumors. The origin and histogenesis of
      these tumors were investigated in the present study. The brain and pineal organ
      of fetal and young transgenic mice less than 3 months old displayed normal
      macroscopic and microscopic features. In 3.5-month-old animals, the pineal organ
      was considerably enlarged due to hyperplasia, finally leading to tumor formation.
      Immunocytochemical demonstration of large T-antigen showed that this oncoprotein
      was already expressed in the nuclei of certain cells in the pineal organ of
      fetuses (16 and 18 days old) and newborn animals, but was absent from all other
      parts of the brain. The immunocytochemical demonstration of S-antigen (arrestin),
      a highly characteristic marker for pinealocytes, was used for further
      characterization of the large T-antigen-immunoreactive cells. The fetal pineal
      organ did not contain immunoreactive S-antigen. This first occurred in certain
      pinealocytes of newborn mice. Double immunostaining revealed that in newborn and
      older transgenic mice the immunoreactive large T-antigen was exclusively found in
      nuclei of cells containing S-antigen immunoreaction in their cytoplasm. Thus,
      transformed pinealocytes appear as stem cells of the experimental tumors. The
      results of this study suggest that primitive neuroectodermal tumors and the
      normal tissue from which they originate share certain molecular and
      immunocytochemical features.

PMID- 1373027
TI  - alpha B-crystallin is present in reactive glia in Creutzfeldt-Jakob disease.
AB  - alpha-Crystallin is a major eye lens protein, composed of two types of subunits,
      alpha A and alpha B. The alpha A subunit is restricted to the lens, but alpha B
      crystallin has recently also been detected in non-lenticular tissues, including
      the nervous system. With the use of a polyclonal antiserum directed against a
      synthetic C-terminal peptide of human alpha B-crystallin, the presence of alpha B
      crystallin could be demonstrated immunohistochemically in astrocytes in the
      brains of patients with Creutzfeldt-Jakob disease (CJD). Most intensive
      localization was observed in the spongiotic tissue representing abundant
      progressively changed astrocytes in CJD. In age-matched control brains weak
      positive reaction was located in individual oligodendroglia cells and subpial
      astrocytes. Prominent increase of alpha B-crystallin in pathological glia in CJD
      may represent a response to stress.

PMID- 1373028
TI  - [Volar plate osteosynthesis in typical and atypical distal radius fractures].
AB  - 28 patients with a fracture of the distal end of the radius were treated by a T
      plate osteosynthesis through the volar approach. There were 7 unstable distal
      metaphyseal fractures and 21 dislocated intra-articular fractures. 21 patients
      were investigated 6 months to 8 years after operation according to the scheme of
      Sarmiento. 17 patients had a good or excellent result, 4 patients a fair or poor
      result. 2 patients developed a Sudeck's dystrophy (Algodystrophy), one of them
      with a radial-ulnar bone bridge. The volar application of the plate is indicated
      for flexion and extension fractures. In cases with compression of the dorsal
      cortex a bone graft is indicated to improve a stable osteosynthesis. A
      conventional tomography on two views helps to diagnose exactly an intra-articular
      fracture and to decide whether to use a plate or pins and external fixation after
      open reduction. Remanipulation or an operation 2 weeks after trauma increases the
      risk of a Sudeck's dystrophy and leads to a poor result.

PMID- 1373026
TI  - Melanotic cerebral ganglioglioma: evidence for melanogenesis in neoplastic
      astrocytes.
AB  - A composite melanotic glial-ganglionic tumor was resected from a 17-year-old girl
      who presented with a 5-year history of epilepsy. Grossly, the tumor was partly
      cystic, partly solid, located superficially in the temporal lobe. Histologically,
      its glial component was composed of spindle and pleomorphic cells, including
      tumor giant cells, which were associated with Rosenthal fibers, eosinophilic
      granular bodies and marked desmoplasia. The cells had immunohistochemical and
      ultrastructural features of astrocytes, and some were invested by incomplete
      basal lamina. Thus, the tumor had many features in common with pleomorphic
      xanthoastrocytoma. However, its most striking feature was the presence of melanin
      pigment in numerous neoplastic cells. Immunoelectron microscopy revealed glial
      fibrillary acidic protein-positive intermediate filaments in tumor cells bearing
      melanosomes and premelanosome, proving their astrocytic nature. This case
      demonstrates, for the first time, melanosomal melanogenesis in human cells with
      astrocytic phenotype, and provides additional evidence for the ability of central
      neuroepithelial cell derivatives to produce melanin.

PMID- 1373029
TI  - Thyroid dysfunction in older persons.

PMID- 1373030
TI  - Controversies in the diagnosis and management of benign prostatic hypertrophy.
AB  - The prevalence of BPH ensures a continuing need for internists to be aware of the
      issues regarding the evaluation and treatment of prostatism, while the developing
      role of nonoperative therapy and the growing recognition of the importance of
      patient preferences have opened the way for an expanded involvement of the
      primary care practitioner in the management of these patients. Prostatism remains
      a difficult clinical problem since many of the symptoms and diagnostic tests are
      nonspecific, especially in the elderly. Basic questions regarding the role of
      bladder outlet obstruction (BOO) in the development of symptoms and in predicting
      outcome from surgery await further study. Against this background of uncertainty,
      however, is the reassurance that the natural history of the process results in
      serious complications in only the minority of patients. Important work is under
      way that will incorporate quality of life outcomes, compare surgery with
      "watchful waiting," and randomize patients to surgical and nonsurgical
      treatments. In the interim, the internist may help patients with prostatism
      significantly by appreciating the natural history of the condition, treating the
      conditions that mimic or exacerbate it, understanding the clinical utility and
      limitations of current evaluation methods, becoming aware of the growing array of
      nonsurgical and minimal-surgery options, and assisting patients in weighing
      therapeutic risks and benefits with their concerns about symptoms.

PMID- 1373031
TI  - [Laser photocoagulation for experimental choroidal neovascularization. 1. Mild
      dye laser photocoagulation].
AB  - The author treated experimentally produced choroidal neovascularization (ChNV)
      with mild dye laser photocoagulation (PHC). We treated these ChNVs with 590 nm
      wavelength, 200 microns spot size, 0.2 second duration and 50 mW of power. Eleven
      eyes of nine rhesus monkeys were used. Then these ChNVs were examined clinically
      and histopathologically at 24 hours, 2 weeks and a month after therapeutic PHC.
      Small ChNVs, less than 1/3 disc diameter healed successfully and
      histopathologically most of them were coagulated and disappeared. A few poorly
      developed ChNVs remained, but were well enveloped by the proliferating retinal
      pigment epithelial (RPE) cells. On the other hand, ChNVs of more than 1/3 disc
      diameter did not respond to weak PHC, grew actively over a month, and were not
      completely surrounded by proliferating RPE cells. These results suggest that by
      mild PHC, small ChNVs may be treatable, however, in large ChNVs, mild PHC may
      rather accelerate their activity.

PMID- 1373032
TI  - Infant neuromotor assessments: a review and preview of selected instruments.
AB  - The advancement of medical technology has produced an increased number of
      surviving neonates. Occupational therapists and physical therapists working in
      neonatal intensive care units and follow-up clinics are faced with the challenge
      of providing early assessment and treatment for this relatively new population of
      infants. The purpose of this article is to review selected infant motor
      evaluation instruments used by therapists and to preview those currently being
      developed. An overview of the historical background of infant neuromotor testing
      is provided, followed by a review of the Infant Neurological International
      Battery (Ellison, Horn, & Browning, 1985) and the Neonatal Neurobehavioral
      Examination (Morgan, Koch, Lee, & Aldag, 1988). Two infant motor tests currently
      being developed, the Chandler Movement Assessment of Infants Screening Test and
      the Miller Infant and Toddler Test (both of which, at the time of this writing,
      are unpublished) are described. Updated information on the psychometric
      properties and the clinical usefulness of these new infant neuromotor tests can
      assist therapists in selecting reliable and valid measures in their clinical
      practice.

PMID- 1373033
TI  - Efficacy and efficiency: self-designed versus instructor-designed study tools.
AB  - During the course of their education, occupational therapy students learn to
      administer complex structured assessments. For easier administration of these
      assessments, students design note cards, which then replace cumbersome test
      manuals during administration. This study considered whether students could learn
      test administration with equal efficiency and efficacy if given test
      administration note cards rather than having to design their own. The results
      showed that the subjects using instructor-designed cards earned written test and
      practical examination scores similar to those of the subjects using self-designed
      cards. The subjects using instructor-designed cards spent significantly less (p =
      .003) total time in study than did the subjects using self-designed cards. The
      difference in time between the two groups was attributable to the time spent
      designing note cards. Therefore, distribution of instructor-designed note cards
      appears to offer equally effective and significantly more efficient learning when
      compared with that produced when students design their own cards. The differences
      in efficacy and efficiency were similar for students of different learning styles
      (as classified by Witkin's field-dependence/field-independence continuum)
      [corrected].

PMID- 1373034
TI  - Should music be used therapeutically in occupational therapy?
AB  - It has long been common knowledge that music profoundly affects human beings on a
      variety of levels. Occupational therapists have at their disposal a potentially
      powerful therapeutic tool, but the specific effects of this tool have not been
      documented. Occupational therapists have a history of using music in their
      treatment, probably to a greater extent than is documented in the literature. It
      would be advantageous for us to engage in research regarding the application of
      music to occupational therapy.

PMID- 1373035
TI  - Gene expression of growth-related proteins and ECM constituents in response to
      unilateral nephrectomy.
AB  - To identify the specific regulatory mechanism associated with the events
      following unilateral nephrectomy, we measured the levels of mRNA encoding for
      extracellular matrix (ECM) constituents, for protooncogenes, and for
      proliferating cell nuclear antigen (PCNA) in renal cortex and glomeruli. One hour
      after left nephrectomy, c-jun and c-fos mRNA levels in renal cortex increased
      rapidly and then decreased rapidly to the control level, whereas c-myc and PCNA
      mRNA levels showed a slower and more sustained increase, with a peak at 6 h after
      nephrectomy, and then decreased to the control level after 7 days. mRNA levels
      for basement membrane components including alpha 1-chain of type IV collagen,
      laminin B1 and B2 chains, and heparan sulfate proteoglycan core protein were
      significantly increased in renal cortex at 12 h after nephrectomy, whereas those
      for interstitial collagens including alpha 1-chains of type I and type III
      collagen were unchanged following nephrectomy. On the other hand, the glomerular
      expression of all genes examined in this study showed little change during the
      experimental period. These results suggest that the time course of mRNA
      expression of ECM constituents is different from that of growth-related proteins
      in renal cortex and that glomerular mRNA levels for these components may not be
      associated with renal hypertrophy in the early stages following unilateral
      nephrectomy.

PMID- 1373036
TI  - Cyclic nucleotide phosphodiesterases from frog atrial fibers: isolation and drug
      sensitivities.
AB  - The cyclic nucleotide phosphodiesterase (PDE) forms present in frog atrial fibers
      were isolated and characterized by their drug sensitivities. DEAE-sephacel
      chromatography of cytosolic PDE activity resolved three major PDE forms: peak A
      hydrolyzed both adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'
      cyclic monophosphate (cGMP) and was activated by calcium-calmodulin (PDE I); peak
      B also hydrolyzed both cAMP and cGMP but was activated by 5 microM cGMP (PDE II);
      peak C specifically hydrolyzed cAMP (PDE IV). Rolipram specifically inhibited PDE
      IV (Ki = 1.1 microM), whereas dipyridamole potently inhibited both PDE II (Ki =
      4.6 microM) and PDE IV (Ki = 0.8 microM). Atrial fiber PDE I was preferentially
      inhibited by zaprinast (Ki = 10 microM). 3-Isobutyl-1-methyl xanthine (IBMX) and
      theophylline inhibited nonspecifically all three different enzymes. The positive
      inotropic drug CI 930 only inhibited the different isolated atrial PDE forms at
      concentrations greater than 200 microM. However, under assay conditions for which
      PDE IV was specifically inhibited (presence of 100 microM rolipram), an IC50 of
      17 microM for CI 930 was observed on the remaining 26% cAMP hydrolytic activity
      of peak C (which could represent a cGMP-inhibited PDE form: PDE III). The same
      PDE forms were also found in frog ventricle. The major difference between frog
      atrial fiber (and ventricular tissue) PDEs and mammalian cardiac PDEs is that the
      main cytosolic cAMP-specific hydrolytic activity in frog heart is due to PDE IV
      rather than PDE III. Rolipram, dipyridamole, and zaprinast might be useful tools
      to investigate the participation of cAMP in frog atrial contraction (unpublished
      observations).

PMID- 1373037
TI  - Use of blue dextran for measuring changes in perfused vascular surface area in
      lungs.
AB  - We investigated the uptake and efflux of Blue Dextran in the isolated perfused
      rabbit lung. Blue Dextran is a high-molecular-weight glucose polymer (original
      mol wt 2 x 10(6) g/mol) containing covalently bonded Reactive Blue 2 dye
      (approximately mmol/g dextran). This blue dye is known for its high binding
      affinity to a wide variety of proteins, with a particularly high affinity for
      serum albumin. In isolated rabbit lungs perfused with a protein-free perfusate,
      both bolus injection and recirculation of Blue Dextran revealed a rapid saturable
      uptake. Once the lungs were loaded with Blue Dextran, efflux of the Blue Dextran
      accumulated in the lungs could be induced by addition of bovine serum albumin
      (BSA) to the recirculating perfusate. The amount of BSA-induced efflux of Blue
      Dextran from the lung was independent of perfusate flow. When the left pulmonary
      artery was ligated after the lungs had been loaded with Blue Dextran, the dye
      induced BSA efflux was only about 50% of normal. Release of the ligature so that
      both lungs were perfused resulted in efflux of the remaining Blue Dextran. The
      combination of high airway pressure and low flow also reduced the dye efflux, and
      the effect was reversed by reducing the airway pressure. With the assumption that
      the high average molecular weight of Blue Dextran confines this molecule to
      interaction with proteins on the vascular surface, the results of this study
      suggest that Blue Dextran uptake and its BSA-induced efflux are proportional to
      the perfused vascular surface area in the lung.

PMID- 1373038
TI  - Systemic and regional O2 delivery and uptake in bled dogs given hypertonic
      saline, whole blood, or dextran.
AB  - The mechanisms by which small volumes of hypertonic saline in dextran (HSD)
      resuscitate bled dogs are incompletely understood but may include a pulmonary
      osmolar reflex. A known negative effect of HSD is hemodilution that reduces O2
      carrying capacity. Our goals in this study were to ascertain whether the putative
      osmotic reflex redistributed blood flow between muscle and gut and whether O2
      delivery (DO2) was adequate at systemic and regional levels. Left hindlimb muscle
      and a segment of ileum were vascularly isolated in three groups (n = 8) of
      anesthetized dogs that were then bled to mean arterial pressure (MAP) of 40 mmHg
      for 30 min. At that point, all shed blood (approximately 40 ml/kg) was returned
      in the blood group (BLD); 20 ml/kg of Dextran 70 was given to the dextran group
      (DEX); and 5 ml/kg of 7.5% NaCl in dextran was given to the HSD group. MAP and
      cardiac output were restored to acceptable levels in all but was poorly
      maintained in HSD. The fall in hematocrit (41 to 25%) in HSD was matched by that
      in DEX (42 to 22%), so that DO2 only reached approximately 55% of that in BLD.
      Nevertheless, systemic and regional O2 uptakes were similar; O2 debt and
      repayment did not differ; and lactate metabolism was alike in all groups. O2
      extraction did have to increase to near maximum in HSD, however. Other than a
      transient increase to muscle, HSD had no special effect on distribution of
      cardiac output. HSD was efficacious as a short-term resuscitative measure but did
      encroach markedly on O2 transport reserves.

PMID- 1373039
TI  - Gene expression in skeletal muscle in response to stretch and force generation.
AB  - Striated muscle is a tissue in which gene expression is influenced to a large
      extent by mechanical signals. This includes the regulation of gene expression
      associated muscle fiber phenotype determination, which depends on which protein
      isoform genes are transcribed, as well as muscle fiber mass accretion, which
      appears to involve some translational regulation. Although muscle synthesizes a
      set of highly specialized proteins it has a remarkable ability to adapt by
      expressing different isoforms of the same protein so that it acquires the
      appropriate contractile characteristics. Our work has focused on the myosin heavy
      chain (HC) genes as these encode the myosin cross bridge, which is responsible
      for muscle intrinsic velocity of contraction and economy of force development.
      RNA analyses after cast immobilization of the limb with the muscle in the
      lengthened or shortened position and/or with electrical stimulation were used to
      determine the effects of altered mechanical signals on gene transcription. When
      the soleus muscle was immobilized in the shortened position in the young animal
      it did not fully differentiate into a slow postural-type muscle. Even in the
      adult, the soleus muscle if deprived of stretch and contractile activity switches
      back to transcribing the fast myosin HC gene. The converse was true when the fast
      rabbit tibialis anterior was subjected to immobilization in the lengthened
      position and/or electrical stimulation. Both stretch alone and stimulation alone
      caused repression of the fast type and activation of the slow myosin genes. The
      reprogramming of the fast muscle was more complete when the stretch was combined
      with stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373041
TI  - Renal nerves modulate kidney renin gene expression during the transition from
      fetal to newborn life.
AB  - The role of renal nerves in regulating changes in plasma renin activity (PRA) and
      renal renin gene expression was studied in intact (n = 6) and denervated (n = 6)
      fetal sheep before birth and during the first 24 h after delivery. Renal
      denervation completely blunted the rise in PRA observed 24 h after delivery in
      newborn lambs; in lambs with intact kidneys, PRA increased significantly (P less
      than 0.05) from 3.26 +/- 0.60 (predelivery) to 6.34 +/- 1.85 ng angiotensin I
      (ANG I).ml-1.h-1 (24 h postdelivery), while in lambs with denervated kidneys,
      predelivery and post-delivery values were 2.84 +/- 0.19 and 2.49 +/- 0.45 ng ANG
      I.ml-1.h-1, respectively. Renin mRNA levels were significantly lower (P less than
      0.001) in denervated than in intact kidneys 24 h after birth. A close analysis of
      these results also revealed that renin mRNA levels were significantly higher (P
      less than 0.001) in intact kidneys of newborn lambs delivered vaginally (n = 3)
      than in newborn lambs delivered by cesarean section (n = 3). These results
      suggest that renal nerves play an important role in regulating renin gene
      expression and PRA during the transition from fetal to newborn life.

PMID- 1373040
TI  - Insulin-like growth factor I preserves host lean tissue mass in cancer cachexia.
AB  - Insulin-like growth factor I (IGF-I) has been implicated in the regulation and
      maintenance of skeletal muscle protein balance and thus may be of potential
      benefit in attenuating the cancer-cachectic process. To examine this hypothesis,
      47 sham or tumor-implanted Fischer 344 rats were randomized to receive either
      continuous subcutaneous IGF-I (220 or 400 micrograms/day) or saline as control.
      In the tumor-bearing (TB) population, IGF-I-treated groups showed a dose
      dependent increase in host weight gain (P less than 0.05), final carcass weight
      (P less than 0.05), and gastrocnemius muscle weights (P less than 0.05) and
      protein contents (0.50 +/- 0.02, 0.40 +/- 0.01, and 0.52 +/- 0.03 g/100 g host
      wt, for non-TB saline, TB saline, and TB 400 mg IGF-I groups, respectively; P
      less than 0.01, IGF-I vs. saline). Similar increases in muscle RNA and DNA
      contents (P less than 0.01) were induced by IGF-I treatment (P less than 0.05).
      IGF-I treatment in this rat sarcoma model significantly reduced the proportion of
      aneuploid cells in the tumor (aneuploid-to-diploid ratio: TB saline 1.1 +/- 0.2
      vs. TB IGF-I 0.5 +/- 0.1; P less than 0.05). IGF-I treatment attenuated host
      muscle protein and lean tissue depletion without stimulation of tumor growth. The
      tumor aneuploid population was reduced in response to IGF-I treatment. Thus IGF-I
      may be a potential therapeutic agent in cancer-induced cachexia.

PMID- 1373042
TI  - Antibody response to the circumsporozoite protein of Plasmodium vivax in
      naturally infected humans.
AB  - The circumsporozoite (CS) protein of Plasmodium vivax consists of a central
      repeat region flanked by highly conserved non-repeat regions. Serum samples from
      33 individuals with naturally acquired infections of P. vivax were tested for
      antibodies to four antigens representing the vivax CS protein. Three recombinant
      proteins containing different overlapping sequences in the non-repeat regions and
      either the entire central repeat region (vivax-1 and vivax-2) or two of the
      repeat sequences (vivax-3) were used as antigens in an enzyme-linked
      immunosorbent assay (ELISA). Antibodies to two other proteins, one (NS1(81)V20)
      containing the entire predominant repeat region (GDRAA/DGQPA) and the other
      (Pvk247) containing the variant repeat sequence (ANGAGNQPG) that was recently
      reported from Thailand were also measured by ELISA. Immunoglobulin G antibodies
      to the antigen representing the predominant repeat were present in 15% of the
      patients on the first day of treatment (day 0) and in 24% of the patients two
      weeks later (post-treatment). Six and 12% of the patients had IgG antibodies to
      the antigen containing the variant repeat on day 0 and post-treatment,
      respectively. A larger proportion of the sera had antibodies to the three
      antigens containing the non-repeat sequences; on the first day of treatment and
      two weeks later, 79 and 97% of the patients, respectively, had antibodies to
      vivax-1, vivax-2, and vivax-3. In this sample of Peruvians naturally infected
      with P. vivax, the most prevalent antibody responses were targeted to epitopes in
      the non-repeat region of the CS protein rather than to epitopes in the repeat
      region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373043
TI  - Sacral resection for control of pelvic tumors.
AB  - A surgical approach for treating patients with resected, recurrent, posterior
      pelvic visceral tumors involving the sacrum is detailed. Of 11 patients, 9 had
      rectal cancers, 1 had chordoma, and 1 had cancer of the cervix. Five total pelvic
      exenterations and five posterior exenterations were performed en bloc with
      involved sacrum. One patient had a sacral resection only. Surgical mortality was
      9%, and the average hospital stay was 1 month. Mean disease-free survival was 1
      year, and mean survival was 3 years. Absolute cure rate was 18% with a complete 5
      year follow-up. This experience confirms the value of this procedure in selected
      patients.

PMID- 1373044
TI  - Primary treatment of hepatocellular carcinoma by arterial chemoembolization.
AB  - Two hundred and ninety-one patients with hepatocellular carcinoma were treated by
      chemoembolization (CE), using ethiodized oil, doxorubicin, and a gelatin sponge.
      Patients with thrombosis of either the portal vein or a main branch were
      excluded. The mortality rate in the first 2 months after treatment was 7% in
      noncirrhotic patients, 2.8% in patients with class A cirrhosis, 8% in patients
      with class B cirrhosis, and 37% in patients with class C cirrhosis. The tumor
      diameter remained the same in 55.3% of patients, was reduced by up to 50% in 20%
      of the patients, was reduced by more than 50% in 7.3% of the patients, and almost
      completely disappeared in 1.8% of the patients. The diameter of the tumor
      increased in 15.6% of patients. Forty-three patients underwent a resection or
      transplantation after chemoembolization. Histologic examination of the specimens
      revealed significant necrosis of the tumor. The long-term survival rate at 2
      years was 49% for class A cirrhotics, 29% for class B cirrhotics, and 9% for
      class C cirrhotics. Complications included cholecystitis (10%), vasculitis (14%),
      renal decompensation (13%), an increase in ascites (14%), and jaundice (12%).
      Chemoembolization is an effective and safe initial treatment for hepatocellular
      carcinoma. It is effective in producing tumor necrosis and reducing the size of
      the tumor. Improvement in survival was noted when patients who underwent
      chemoembolization were compared with an historical series of untreated patients,
      and resection and transplantation are kept as options.

PMID- 1373045
TI  - Controversy over the benefit of hyperbaric oxygen to wound healing and
      angiogenesis in radiation-damaged tissue.

PMID- 1373046
TI  - Direct measurement of fast axonal organelle transport in chronic ethanol-fed
      rats.
AB  - While indirect methods have been used, direct evaluation and measurement of the
      fast axonal transport system itself in chronic ethanol-fed rats have not been
      carried out previously. We evaluated this system using analog and digital image
      enhancement of differential interference contrast optical images in real time to
      assess the effect of ethanol on fast intra-axonal organelle traffic in rat sural
      nerve. A radiolabeling method for evaluating fast axonal transport was used in
      similar animals to compare the indirect and direct techniques. Also, the
      concentration of organelles (mitochondria, large and small clear vesicles, dense
      vesicles, and membranous whorls) in the annulospiral sensory nerve endings of
      muscle spindles from a foot muscle (flexor digitorum brevis) of these same
      animals was quantitated from electron micrographs. Rats were fed an ethanol
      containing liquid diet for one to five months. Three observations were made; (1)
      There was no statistically significant change in the mean organelle speed in the
      anterograde direction, but the mean organelle speed in the retrograde direction
      increased 11%, 9%, and 17% (statistically significant) at 3, 4, and 5 months of
      ethanol exposure, respectively. (2) Significant increases in organelle content of
      sensory nerve endings were seen at 2 and 3 months of intoxication. (3) Increases
      in organelle densities in terminals were transitory and returned to normal in the
      face of on-going ethanol administration. We conclude: (1) There is no permanent
      impairment of fast axonal organelle transport in this model after 5 months of
      exposure. (2) Sensory endings on muscle spindles show transitory increases in
      organelle density. (3) Retrograde speed increases may be a partial compensatory
      mechanism to help restore normal terminal organelle density.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1373047
TI  - Effect of histamine antagonists and agonists on IgE production in mice.
AB  - This study was undertaken to investigate the effect of histamine, its receptor
      antagonists and agonists on IgE antibody production in mice. BALB/c mice were
      immunized intraperitoneally with 1 mg alum plus 30 micrograms of Ag90, the
      antigen of Japanese occupational asthma. Histamine receptor antagonists were
      administered before the immunization and simultaneous injection of histamine. The
      mice were bled 14 days after immunization and anti-Ag90 IgE antibody was
      obtained. Titers of the antisera were measured by passive cutaneous anaphylaxis
      reaction in Sprague-Dawley rats. Treatment with histamine only did not affect the
      level of specific IgE antibody. Administration of H1 antagonist or H2 agonist
      suppressed IgE production significantly. In contrast, treatment with H2
      antagonist or H1 agonist augmented the IgE antibody production. Injection of H1 +
      H2 antagonists had no effect on the antibody production. These results suggest
      that histamine suppressed specific IgE production via H2 receptors and enhanced
      it through H1 receptors in the induction phase of the system.

PMID- 1373048
TI  - Relationship between allergen-specific skin testing and nasal provocation in
      patients with perennial rhinitis.
AB  - Patients with perennial rhinitis were evaluated by allergen challenge
      epicutaneously and intranasally. Nasal provocation was assessed by clinical
      score, graded 0-12, to include rhinomanometry, secretions (mL), sneezes, and
      stuffy nose. All 40 patients with perennial symptoms had no clinical history of
      seasonal exacerbations but did have both positive skin tests and nasal
      provocation to the same allergen. Skin test wheel size correlation with nasal
      provocation (P less than .02).

PMID- 1373050
TI  - [A case of locally advanced esophageal cancer effectively treated with concurrent
      chemotherapy and radiotherapy].
AB  - A case of a 69-year-old man with locally advanced esophageal cancer was reported.
      The patient received five courses of chemotherapy consisting of cisplatin (30 mg
      i.v. days 1-5), 5-fluorouracil (500 mg i.v. days 1-5) and bleomycin (5 mg i.m.
      days 1-5) every four weeks with a split course irradiation at a dose of 50 Gy,
      which was concurrently given at the second, third and fourth course of the
      chemotherapy. Treatment was effectively carried out without severe toxicities.
      The patient achieved a histologically-confirmed complete remission after
      completion of the treatment. The patient is disease-free and fully active 28
      months after the beginning of chemotherapy. The treatment modality appears to be
      useful for advanced esophageal cancer.

PMID- 1373049
TI  - [A case of verrucous carcinoma of the tongue, effectively treated with
      preoperative chemotherapy (UFT, CDDP, PEP) and irradiation].
AB  - A 70-year-old male complained of a mass on the left side of his tongue. A biopsy
      specimen was diagnosed as verrucous carcinoma. He was treated with preoperative
      chemotherapy (UFT, CDDP, PEP) and irradiation, continuous partial glossectomy.
      The tumor response to chemotherapy was excellent, and no tumor cells were found
      in the surgical specimen. There was no recurrence of the tumor 1 year and 7
      months after therapy. For advanced tumors, preoperative chemotherapy appears to
      be significantly effective.

PMID- 1373051
TI  - [Successfully treated locally advanced breast cancer by intra-arterial infusion
      chemotherapy: a case report].
AB  - A 40-year-old female was admitted to our hospital with a large right breast tumor
      that was over 15 cm in diameter. We treated this locally advanced breast cancer
      by intra-arterial infusion chemotherapy. Through a catheter placed in the right
      subclavian artery, doses of 20-30 mg of ADM were injected intermittently with MMC
      and 5-FU. When a total of 120 mg of ADM had been infused, leukopenia developed,
      but this was immediately improved by G-CSF. With this treatment, her breast tumor
      and lung metastases were almost completely disappeared. Thus, an intra-arterial
      infusion chemotherapy was considered to be an effective treatment for locally
      advanced breast cancer.

PMID- 1373052
TI  - [Experimental study of CF chemotherapy, combined with another one
      chemotherapeutic drug against head and neck cancer cell lines].

PMID- 1373053
TI  - Terminal dehydration, a compassionate treatment.

PMID- 1373054
TI  - Biochemical changes in kidneys of normal and stone forming rats with sodium
      pentosan polysulphate.
AB  - The influence of sodium pentosan polysulphate was studied on the deposition of
      stone forming constituents along with certain enzymes in the renal tissue of
      experimentally induced urolithiatic rats. Calcium, oxalate and phosphorus levels
      were elevated in kidneys of lithogenic rats, while SPP administration reduced
      these levels to near control values. The elevation in kidney LDH was significant
      in the stone forming groups and SPP had minimal effect. Increases in the
      activities of Na+, K(+)-and Ca(2+)-ATPases in the calculogenic groups was lowered
      considerably with SPP treatment. Inorganic pyrophosphatase activity was reduced
      significantly in the calculogenic as well as in the drug treated groups. Leucine
      aminopeptidase was decreased in the calculogenic group. SPP treatment elevated
      the enzyme activity in the treated groups. Reduction in kidney oxalate with SPP
      may prove useful in the medical management of urolithiasis.

PMID- 1373055
TI  - The birth symbol in traditional women's art.

PMID- 1373056
TI  - Semiautomatic quantification of silver-stained nucleolar organizer regions in
      tissue sections and cellular smears.
AB  - Silver staining of nucleoli reveals argyrophilic proteins associated with
      nucleolar organizer region (Ag-NOR) proteins. Argyrophilic components appear as
      dots about 1 micron in diameter dispersed throughout the nucleolus (Ag-NOR dots).
      The count of Ag-NOR dots is a useful index for improving the cancer diagnosis and
      determination of prognosis. Here we describe software developed on a medium-cost
      image analyzer in order to evaluate the mean area of NORs and their number
      relative to an internal reference, the number and areas of clusters of NORs and
      the area of the nucleus. Statistical analysis of the data was performed during
      counting. The first application concerned counting NOR dots during mitosis in
      cell imprints; those counts were 2.3, 15.3 and 55.56 for the metaphase, telophase
      and interphase, respectively (relative to unitary dots of metaphase cells). In
      the second application we demonstrated a significant difference in NOR numbers
      between two groups of prostatic cancers with good and poor prognoses (6.05 +/-
      2.79 SD and 7.96 +/- 3.01, respectively; with Student's t test, = 1.999; P =
      .05).

PMID- 1373057
TI  - Influence of cell cycle synchronization on digital image analysis of HL-60
      granulopoiesis.
AB  - Retinoic acid (RA)-treated HL-60 cells subjected to density arrest (DA) and
      double thymidine block (TB) synchronization demonstrated image feature changes
      associated with cellular proliferation and differentiation. RA-treated TB cells
      demonstrated an increased level of morphologic differentiation (assessed by
      differential counts and quantitation of nuclear shape) and more rapid functional
      differentiation (assessed by superoxide production and expression of complement
      receptors) than RA-treated DA cells. By comparison to DA cells, TB cells had less
      variation in virtually all image features values. A Kruskal-Wallis test of image
      features ranked total optical density (TOD) of Feulgen-stained cells, nuclear
      area and shape factor as the top three features regardless of synchronization
      method. Statistically significant changes in image feature values of RA-treated
      cells were first noted on day 1. The computer-assisted ability to discriminate RA
      treated cells on a given day after induction from paired controls by means of an
      unsupervised learning algorithm increased over a seven-day period for both DA and
      TB cells. However, in the dichotomous (RA-treated versus untreated)
      classification scheme employed, which did not account for continuous levels of
      morphologic differentiation, there was no advantage in the use of the TB over DA
      procedure.

PMID- 1373058
TI  - Double reactivity of monoclonal and polyclonal rheumatoid factors for IgG and
      histones: mapping of binding sites by means of histone synthetic peptides and
      anti-Id antibodies.
AB  - Polyreactive antibodies able to bind various apparently unrelated structures
      represent a frequent antibody population in autoimmune diseases. In this work,
      the structural basis of the double reactivity of such autoantibodies was
      investigated using as models polyclonal and monoclonal human rheumatoid factors
      (RF) reacting with histones. Both direct ELISA binding and competitive inhibition
      experiments were performed. A more precise delineation of the histone regions
      recognized by the RFs was made by means of 27 synthetic peptides of these
      proteins. Anti-idiotope (Id) murine antibodies were used to map the binding sites
      involved on RF in the interaction with IgG and histones. Among the 13 polyclonal
      and six monoclonal RFs tested, four and two respectively were found to cross
      react with IgG and histones. The fragments shown to be the most frequently
      recognized by RFs were located in residues 1-16 and 204-218 of H1, 1-20 and 65-85
      of H2A, and 1-21 of H3. The results obtained by competitive ELISA assays using
      IgG, histone peptides and anti-Id monoclonal antibodies led us to confirm and
      characterize more precisely our previous finding suggesting the existence of
      topographically distinct binding sites for the different targets recognized by
      RFs.

PMID- 1373059
TI  - Induction of intercellular adhesion molecule-1 but not of lymphocyte function
      associated antigen-3 in thyroid follicular cells.
AB  - We investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and
      lymphocyte function-associated antigen-3 (LFA-3) by thyrocytes and their
      regulation by cytokines. Immunofluorescence studies on cryostat sections and on
      freshly dispersed cell preparations showed that ICAM-1 and LFA-3 are barely
      detectable in non-autoimmune thyrocytes. However, thyrocytes acquired ICAM-1
      expression in culture. IFN-gamma, IL-1 beta and TNF-alpha produced a clear
      enhancement of ICAM-1 expression. When tested in combination, IL-1 beta and TNF
      alpha were additive to the IFN-gamma effect. LFA-3 expression was not modulated
      by these cytokines. In the HT93 thyroid cell line generated by transfection with
      SV40, ICAM-1 and LFA-3 were both constitutively expressed at high levels.
      Cytokines modulated ICAM-1 expression similarly, but to a greater extent than in
      normal thyrocytes. LFA-3 remained unmodified. These results support the notion
      that normal thyrocytes are immunologically silent cells. The capability of
      cytokines to induce ICAM-1 together with HLA class I and class II-expression on
      thyrocytes suggests that under their influence, these cells may express all the
      surface molecules required for antigen presentation and/or for being recognized
      as target cells in the context of thyroid autoimmune disease.

PMID- 1373060
TI  - A common epitope on human tumor necrosis factor alpha and the autoantigen 'S
      antigen/arrestin' induces TNF-alpha production.
AB  - A common epitope on S-antigen (arrestin), a potent autoantigen inducing
      experimental autoimmune uveoretinitis (EAU), and on human tumor necrosis factor
      alpha (hTNF alpha) was revealed using two monoclonal antibodies to S-antigen
      which inhibit EAU induction. The minimal common sequence for monoclonal antibody
      recognition is GVxLxD in the S-antigen/hTNF alpha amino acid sequences. Peptides
      containing this sequence motif exhibited monocyte activating capacity similar to
      the autocrine stimulatory capacity of hTNF alpha itself. In the S-antigen this
      activity was located from residue 40 to 50, corresponding to the peptide
      PVDGVVLVDPE (epitope S2). In hTNF alpha, the monocyte activating capacity
      correlated to residue 31 to 53, corresponding to the peptide
      RRANALLANGVELRDNQLVVPSE (peptide RRAN). The identified regions define common
      functional structures in the autoantigen and in the hTNF alpha molecule. The data
      suggest a regulatory function of this particular structure in TNF alpha
      expression and in autoimmunity.

PMID- 1373061
TI  - T helper function of CD4+ cells specific for defined epitopes on the
      acetylcholine receptor in congenic mouse strains.
AB  - We previously identified sequence segments of Torpedo acetylcholine receptor
      (TAChR) alpha subunit recognized by CD4+ cells of congenic mouse strains of
      different H-2 haplotypes, susceptible to experimental autoimmune myasthenia
      gravis. CD4+ cells from BALB/c and CB17 mice (H-2d) recognized the peptide
      sequences alpha 1-20 and alpha 304-322, while C57BL/6 and BALB/b mice (H-2b)
      recognized alpha 150-169 and alpha 360-378. C57BL/6 mice recognized to a lesser
      extent also peptide alpha 181-200. In the present study we demonstrate that CD4+
      cells which recognize these epitopes have T-helper function. CD4+ cells from
      TAChR immunized mice, stimulated in vitro with synthetic epitope peptides,
      induced proliferation in vitro of B cells via soluble factors which were not
      strain specific, and induced secretion in vitro of anti-AChR antibodies. Upon in
      vitro stimulation with T-epitope peptides, they secreted interleukin-2.
      Immunization of mice with synthetic T-epitope peptides caused sensitization of
      CD4+ cells, which responded in vitro both to the immunizing peptides and to
      TAChR, and appearance of anti-AChR antibodies in vivo, further identifying the
      epitope-specific CD4+ cells as AChR-specific T-helper cells.

PMID- 1373062
TI  - Alkyllysophospholipid prevents induction of experimental allergic
      encephalomyelitis.
AB  - Alkyllysophospholipids are synthetic analogues of natural phospholipids
      possessing a high immunomodulating and antitumoral capacity. Experimental
      autoimmune encephalomyelitis is a model disease for multiple sclerosis which can
      be induced by injecting rats with myelin basic protein, MBP. The effect of one
      alkyllysophospholipid, ET-18-OCH3, on the course of experimental autoimmune
      encephalomyelitis was investigated. It was found that animals treated with ET-18
      OCH3 showed only weak signs of disease. MBP specific T-cell lines were co
      cultivated with ET-18-OCH3. The compound suppressed T-cell proliferation
      markedly, suggesting that this might be its mode of action in vivo. Since ET-18
      OCH3 has only low toxicity in man, it could be of interest to perform further
      studies on its effects on autoimmune, demyelinating disease.

PMID- 1373063
TI  - Four distinct antigenic regions are present in the primary structure of HIV-1 and
      HIV-2 proteinases.
AB  - OBJECTIVE: The purpose of this study was to assay reactivity of antibody-positive
      sera to different parts of the HIV-1 and HIV-2 proteinase (PR) proteins. DESIGN:
      Since the majority of HIV-1-antibody-positive sera react to the proteinase, but
      the antigenic determinants on the protein have not been identified, we attempted
      to identify these determinants. INTERVENTIONS: We synthesized 18 peptides
      representing the PR of HIV-1 and HIV-2 in order to map serum reactivity to the PR
      protein. RESULTS: Both HIV-1- and HIV-2-antibody-positive sera recognized four
      distinct antigenic regions in the HIV-1 and HIV-2 PR. CONCLUSIONS: Correlation
      between our results and the crystallographic structure of the protein revealed
      that the antigenic regions are positioned at the surface of the HIV-1 PR.
      Although the structure of HIV-2 PR has not yet been characterized, our results
      indicate that the folding of the HIV-1 and HIV-2 PR may be very similar.

PMID- 1373064
TI  - Effect of isoprinosine on HIV antigenaemia.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of isoprinosine
      on HIV-antigen expression in HIV-positive patients without AIDS. DESIGN: Serum
      samples from anti-HIV-positive patients without AIDS participating in a double
      blind, placebo-controlled trial of isoprinosine in the treatment of HIV infection
      were analysed for the presence of HIV antigen. SETTING: Data and samples were
      collected from the 21 medical centres who participated in the Scandinavian
      multicentre placebo-controlled isoprinosine study. PATIENTS, PARTICIPANTS:
      Samples were available from 19 of 21 participating centres. Of 866 patients who
      enrolled, baseline serum samples were available for 642 (74%; 308 isoprinosine-
      and 334 placebo-treated patients). INTERVENTIONS: Treatment was 1 g isoprinosine
      administered orally three times a day or matching placebo for 24 weeks. MAIN
      OUTCOME MEASURES: Comparison of HIV-antigen levels before and during treatment in
      both the isoprinosine-treated group and the placebo-treated group of patients.
      RESULTS: During the study, AIDS developed in 19 patients; 17 of whom were
      receiving placebo treatment and two isoprinosine. The proportion of HIV-antigen
      positive patients developing AIDS during treatment was significantly different
      from the proportion of HIV-antigen-negative patients in whom AIDS developed (6
      versus 2%; P = 0.02). No significant changes in HIV-antigen levels were observed
      between the isoprinosine- and the placebo-treated group of HIV-antigen-positive
      patients. Median HIV-antigen levels did not change significantly in either the
      isoprinosine- or the placebo-treated group. CONCLUSION: Our results suggest that
      isoprinosine does not have antiviral activity against HIV in vivo.

PMID- 1373065
TI  - The bleomycin resistance gene of transposon Tn5 is an excellent marker for
      transformation of corynebacteria.
AB  - Corynebacteria are highly sensitive to the glycopeptide antibiotic bleomycin. The
      bleomycin resistance gene of transposon Tn5 is expressed very efficiently in
      Brevibacterium lactofermentum. This gene constitutes an excellent marker for
      selection of transformants of corynebacteria. The bleomycin resistance gene is
      expressed from the same promoter as the neomycin resistance gene, which is
      already used as marker in many vectors of corynebacteria. The promoter of the neo
      ble cluster is expressed in a variety of Gram-negative and Gram-positive
      microorganisms and eucaryotic organisms.

PMID- 1373066
TI  - Intermediate filament molecular biology.
AB  - Epidermal keratin intermediate filaments appear to have a structural function.
      The functions of other intermediate filaments are being elucidated using a
      combination of molecular genetic methods, including the expression of dominant
      negative mutant proteins and gene targeting. The differential expression of
      intermediate filament genes is regulated by both the accessibility of multiple
      regulatory elements and the activity or level of multiple positive and negative
      transcription factors.

PMID- 1373067
TI  - Slow axonal transport.
AB  - New studies provide further evidence that the neuronal cytoskeleton is the
      product of a dynamic interplay between axonal transport processes and locally
      regulated assembly mechanisms. These data confirm that the axonal cytoskeleton in
      mammalian systems is largely stationary and is maintained by a smaller pool of
      moving subunits or polymers. Slow axonal transport in certain lower species,
      however, may exhibit quite different features.

PMID- 1373068
TI  - Intermediate filament structure.
AB  - In the past year, several new developments concerning the structure of
      intermediate filament proteins and their assembly into intact intermediate
      filaments have been made: the coiled-coil structure of a rod domain has been
      elucidated; the basis of the chain interaction and its role in intermediate
      filament assembly has been specified; the organization of nearest-neighbour
      molecules in keratin intermediate filaments has been determined; and the glycine
      loop structures of the terminal domains of epidermal keratin chains have been
      defined. In addition, mutations in intermediate filament chains that promote
      pathology have been reported for the first time.

PMID- 1373069
TI  - Oncogene RNA expression in three human lymphoblastic leukemia cell lines
      lymphocytes.
AB  - We have explored the RNA oncogene expression by three human acute lymphoblastic
      leukemia lines, NALM-6, MOLT-3, and REH. We compared such expression with that of
      normal human lymphocytes. Marked differences in the RNA expression of the third
      exon of c-myc, v-myb, v-Hras, N-ras, v-fes, and v-fos were found. We noted
      minimal or no differences in the RNA expression of v-abl, B-lym, v-erb-B, c-ets,
      v-fms, v-kras, v-mos, v-raf, and v-sis.

PMID- 1373070
TI  - Transcriptional down-regulation of c-myc in human prostate carcinoma cells by the
      synthetic androgen mibolerone.
AB  - The mechanism of down-regulation of c-myc RNA associated with androgen-induced
      suppression of the transformed phenotype in the human prostate carcinoma cell
      line LNCaP was investigated. The synthetic androgen mibolerone (7 alpha-17 alpha
      Dimethyl-19-nortestosterone) reversibly inhibits the proliferation of LNCaP cells
      and, from 12-72 h after hormone addition reduces the level of c-myc transcripts
      to a few per cent of controls. P1, P2, and P0 c-myc transcripts decline at the
      same rate, whereas P3 transcripts are much less hormone sensitive. Nuclear run-on
      analysis revealed that c-myc is down-regulated at the level of transcription
      initiation in LNCaP cells. The level of c-myc transcripts prevailing in untreated
      control cells can be restored in androgen-induced cells by excess antiandrogen,
      indicating the involvement of the androgen receptor in c-myc down-regulation.

PMID- 1373072
TI  - Serotoninergic stimulation of aldosterone secretion in vivo: role of the
      hypothalamo-pituitary adrenal axis.
AB  - The control of aldosterone secretion in vivo by serotonin was studied in
      conscious rats. Serial blood samples were taken from indwelling arterial cannulae
      before and after i.p. administration of 1 ml (4 g/l) 5-hydroxytryptophan (5-HTP),
      the precursor of serotonin (5-HT), or saline, and analysed for 5-HTP, serotonin,
      5-hydroxyindoleacetic acid, plasma renin activity (PRA), corticosterone,
      aldosterone, sodium and potassium concentration. The relative contribution of the
      hypothalamo-pituitary adrenal axis was investigated in animals pretreated with
      the synthetic glucocorticoid dexamethasone. 5-HTP caused a significant increase
      in all parameters within 45 min except for plasma sodium and potassium. Saline
      administration showed no significant effect. Dexamethasone pretreatment
      significantly impaired the corticosterone and aldosterone response to 5-HTP,
      although the aldosterone response was merely attenuated. No other parameter was
      affected by dexamethasone pretreatment. The results show that administration of 5
      HTP, which increases serum serotonin levels, stimulates PRA, corticosterone and
      aldosterone secretion. Dexamethasone pretreatment inhibits the aldosterone
      response, though not completely, suggesting that the stimulatory action of 5-HTP
      involves the release of ACTH, which stimulates corticosterone and aldosterone
      secretion by the adrenal cortex. The failure of dexamethasone to block the
      aldosterone response completely, suggests the involvement of other mechanisms
      such as the renin-angiotensin system or a direct action of serotonin on the
      adrenal zona glomerulosa.

PMID- 1373071
TI  - In vitro effects of substance P analogue [D-Arg1, D-Phe5, D-Trp7,9, Leu11]
      substance P on human tumour and normal cell growth.
AB  - Analogues of the neurotransmitter substance P (SP) can interact with neuropeptide
      receptors, and are reported to inhibit growth of small cell lung cancer cell
      lines (SCLC CLs). We found [D-Arg1, D-Phe5, D-Trp7,9, Leu11] substance P (D
      Phe5SP) significantly inhibited DNA synthesis by 10/10 human tumour CLs; six
      SCLC, one N-SCLC (squamous), two ovarian and one squamous cervical carcinoma,
      with inhibition to 50% control levels (IC50) of 20-50 microM. There was dose
      dependent inhibition of colony forming efficiency (CFE) in 3/3 SCLC and 1/1 N
      SCLC CL, IC50s of 0.5-6.5 microM in 5% serum. Exposure of SCLC CL HC12 to 100
      microM D-Phe5SP for 1-4 h caused a progressive fall in viable cell number;
      surviving cells, grown in the absence of peptide, showed a decreased growth rate.
      During 1 week's exposure of two SCLC CLs to 20 microM D-Ph5SP, growth was slower
      than control cultures, while 50-100 microM completely inhibited growth. These
      inhibitory effects were partially reversed by increasing serum concentration from
      5 to 20%, but not by SP, vasopressin, bombesin or insulin-like growth factor 1.
      There was some inhibition of CFE by 3/3 normal human bone marrows, IC50s of 30-80
      microM, compared with 8 microM for HC12 in 20% FCS. Therefore D-Phe5SP appears to
      have more potent antiproliferative effects in tumour cells than normal cells,
      suggesting a role for this analogue in tumour treatment.

PMID- 1373073
TI  - Androgens and androgen-receptors in prostate tissue from patients with benign
      prostatic hyperplasia: effects of cyproterone acetate.
AB  - Testosterone, 5 alpha-dihydrotestosterone and cyproterone acetate (CPA) were
      estimated in samples of prostate tissue, obtained from benign prostatic
      hyperplasia (BPH) patients who were or were not pretreated with CPA. Furthermore,
      these steroids were estimated in various fractions of the BPH tissue, and the
      number of nuclear androgen-receptor sites was determined. CPA-treatment caused a
      4-fold, significant suppression of 5 alpha-dihydrotestosterone levels in total
      prostate tissue and its subfractions, without affecting testosterone levels or
      the androgen-receptor contents of the nuclear extracts. Nuclear concentrations of
      CPA were twice as high as those of 5 alpha-dihydrotestosterone. It is concluded
      that effects of CPA may have been caused through a combination of the following
      mechanisms: (1) suppression of peripheral androgen levels; (2) competition with
      androgens for (nuclear) androgen-receptors; and (3) suppression of prostatic 5
      alpha-reductase.

PMID- 1373074
TI  - Involvement of the macrophage low density lipoprotein receptor-binding domains in
      the uptake of oxidized low density lipoprotein.
AB  - Macrophages, unlike most other cells, possess both low density lipoprotein (LDL)
      and scavenger receptors. The scavenger receptor has been shown to mediate the
      uptake of oxidized LDL (ox-LDL), which ultimately leads to cholesterol loading of
      the macrophages. The present study was undertaken to define epitopes on ox-LDL
      that are important for lipoprotein binding to macrophages and to ascertain
      whether ox-LDL can bind to the LDL receptor. Monoclonal antibodies (Mabs)
      directed against several epitopes along the apolipoprotein B-100 (apo B-100)
      molecule were used. LDL (300 micrograms/ml) was oxidized by incubation with 10
      microM CuSO4 for 24 hours. Ox-LDL, as opposed to acetylated LDL (ac-LDL), reacted
      with Mabs directed against the LDL receptor-binding domains (Mabs B1B6 and B1B3).
      Similarly, uptake of ox-LDL but not ac-LDL by a murine J774 macrophage-like cell
      line was inhibited by as much as 40% after using Mab B1B6. The anti-LDL receptor
      antibody IgG-C7 also inhibited 125I-ox-LDL uptake by macrophages by 60%.
      Chromatography on heparin-Sepharose columns of LDL that was partially oxidized
      for only 3 hours resulted in two fractions: an unbound fraction with
      characteristics similar to those of ox-LDL and a bound fraction similar to native
      LDL. Macrophage degradation of the unbound fraction was inhibited by Mab IgG-C7
      and Mab B1B6, which are directed toward the LDL receptor and the LDL receptor
      binding domains on apo B-100, respectively. When incubated with three types of
      macrophages, J774 macrophage cells, mouse peritoneal macrophages, and human
      monocyte-derived macrophages, excess amounts of unlabeled ox-LDL, like native LDL
      but unlike ac-LDL, substantially suppressed the uptake and degradation of 125I
      labeled LDL. Similar studies with fibroblasts, however, revealed that unlabeled
      LDL but not unlabeled ox-LDL or ac-LDL competed with 125I-LDL for cellular uptake
      and degradation. Mab directed against epitopes on the amino terminus domain of
      apo B-100 (C14) demonstrates a similar immunoreactivity with ox-LDL and native
      LDL but a much lower reactivity with ac-LDL. Mab C14 inhibited macrophage
      degradation of ox-LDL by 34% but had no inhibitory effect on the uptake of native
      LDL or ac-LDL. Thus, the ac-LDL and LDL receptor-binding domains as well as a
      unique epitope on the amino terminus of apo B-100 may be involved in macrophage
      binding of ox-LDL.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1373075
TI  - Collagens in human atherosclerosis. Immunohistochemical analysis using collagen
      type-specific antibodies.
AB  - This study represents a systematic analysis of the distribution of collagen types
      in human atherosclerotic lesions. Formalin-fixed, paraffin-embedded aortic
      tissues of 40 lesions from 16 different individuals ranging in age from 1 month
      to 84 years were examined immunohistochemically using antibodies to type I, III,
      IV, V, and VI collagens. Preembedding immunoelectron microscopy was used to
      simultaneously localize type V and VI collagens within the lesions. Localization
      of type III collagen was very similar to that of type I, and type VI collagen
      appeared together with these two types of collagen in the thickened intimas of
      all stages of the lesion. Type V collagen was not detected in either fatty
      streaks or the mild intimal thickening of the aortas of children. With advancing
      age and lesion progression, the immunoreactivity with anti-type V collagen
      antibody became more intense. Type IV collagen was detected in the basement
      membrane region of intimal cells. In advanced lesions thick deposits of type IV
      collagen were found around the elongated smooth muscle cells. Using
      immunoelectron microscopy, type V collagen was found to be localized to cross
      banded collagen fibers, and type VI collagen was found to be localized to beaded
      filaments present throughout the interstitium of the thickened intima. These
      findings suggest that collagens preserve the pathophysiological and functional
      integrity of the vascular wall by providing mechanical support as well as
      assuring the proper interaction of cells during the formation of atherosclerotic
      lesions.

PMID- 1373076
TI  - Anionic currents of chick sensory neurons are affected by a phospholipase A2
      purified from the venom of the taipan snake.
AB  - A neurotoxic phospholipase A2 was purified from the venom of the taipan snake
      Oxyuranus scutellatus scutellatus by three consecutive chromatographic steps on
      ion exchange resins, followed by an affinity column prepared with a
      phosphatidylcholine derivative attached to Sepharose. The phospholipase was shown
      to be of type A2 (specific activity of 85 units/mg protein), and an apparent
      molecular weight of 16,000. Amino acid analysis shows the presence of approx. 150
      residues with the N-terminal amino acid sequence: NLAQFGFMIRCANGGSRSALDYADYGC,
      different from all the phospholipases described until now. This enzyme is lethal
      to experimental mice (LD50 = 10 micrograms/20 g mouse weight) and affects ionic
      currents in chick (Gallus domesticus) dorsal root ganglion cells, measured by the
      whole-cell clamp technique. In symmetrical external/internal ionic solutions,
      after suppression of Na+, K+ and Ca2+ currents, external application of
      phospholipase at a low concentration (30 nM) was shown to increase the baseline
      current in a reversible manner. The augmented response was voltage-dependent and
      the effect was much greater for negative currents. In the presence of a salt
      gradient across the membrane (out 40 mM NaCl/in 140 mM CsCl), the current
      reversal potential revealed a shift in the positive direction typically due to Cl
      ion flux through the membrane. External application of a 50 microM concentration
      of picrotoxin caused a reversible reduction of the phospholipase-induced chloride
      current. Moreover, no appreciable current block was detected after addition of 50
      microM DIDS.

PMID- 1373077
TI  - A human skeletal muscle cell line obtained from an adult donor.
AB  - A cell line (RCMH) in permanent culture was established from surgically removed
      adult normal human skeletal muscle by exposure to conditioned media obtained from
      thyroid cells. Cells proliferated indefinitely but displayed density inhibition
      of growth while maintaining some differentiated markers. Under certain incubation
      conditions, cells fused into myotube-like structures, with a concomitant increase
      in muscle specific proteins, such as human myoglobin, skeletal muscle myosin,
      desmin and dystrophin, as identified using immunocytochemical procedures. In
      addition, RCMH cells displayed high affinity receptors for alpha-bungarotoxin
      (Bmax = 0.7 pmol/mg protein, Kd = 1.5 nM) and dihydropyridines (Bmax = 0.3
      pmol/mg protein, Kd = 0.5 nM for [3H]PN200-110); these values are comparable to
      those reported for muscle cells in primary culture. Patch-clamp studies showed
      the presence of 42 pS carbachol gated channels and of 5 pS calcium channels
      (current carried by barium); chloride and potassium channels were also seen. This
      new cell line appears to be a convenient model system to study skeletal muscle
      function.

PMID- 1373078
TI  - Relationship between cytosolic Ca2+ concentration and amylase release in rat
      parotid acinar cells following muscarinic stimulation.
AB  - Carbachol (CCh), a muscarinic-cholinergic agonist, increased both cytosolic free
      calcium concentration ([Ca2+]i) and amylase release in rat parotid acinar cells
      or acini in a dose-dependent manner. Treatment of acinar cells with the
      intracellular Ca2+ antagonist, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate
      (TMB-8), or the intracellular Ca2+ chelator, 1,2-bis(O-aminophenoxy)ethane
      N,N,N'N'-tetraacetic acid (BAPTA), strongly attenuated the increases in [Ca2+]i
      evoked by CCh, but amylase release from acini was not significantly suppressed by
      the treatment with TMB-8 or BAPTA. Low concentrations (0.02-0.5 microM) of
      ionomycin, a Ca2+ ionophore, caused increases in [Ca2+]i comparable to those
      induced by CCh, but the same concentrations had only a little effect on amylase
      release. The protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate
      (TPA), stimulated amylase release in quantities similar to those induced by CCh,
      although TPA alone did not cause any change in [Ca2+]i. Combined addition of TPA
      and ionomycin potentiated only modestly amylase release stimulated by TPA alone.
      Staurosporine, a protein kinase C-inhibitor, similarly inhibited both the CCh-
      and TPA-induced amylase release. These results suggest that an increase in
      [Ca2+]i elicited by CCh does not play an essential role for inducing amylase
      release in rat parotid acini. Amylase release by muscarinic stimulation may be
      mediated mainly by activation of protein kinase C.

PMID- 1373079
TI  - Topographic relationship between senile plaques and cerebrovascular amyloidosis
      in the brain of aged dogs.
AB  - The distributions of senile plaques (SP) and cerebrovascular amyloidosis (CA)
      were studied by employing thioflavin S and modified Bielschowsky stains, and beta
      protein immunohistochemistry on serial sections of the brains of aged dogs older
      than 10 years. Mature and perivascular plaques, both of which contained compact
      amyloid deposits, always showed a close topographic relationship to CA. In
      contrast, the majority of diffuse plaques showed no topographic relationship to
      CA. Cell bodies of neurons and/or glia were almost always involved in the diffuse
      plaques. In addition, beta-protein immunohistochemistry demonstrated amyloid
      deposits on the periphery of occasional neurons. These findings suggest that
      different mechanisms may be involved in the development of the different subtypes
      of SP in the brains of aged dogs.

PMID- 1373080
TI  - Blood chemistry investigated in budgerigars.

PMID- 1373081
TI  - Differential gene expression during germination and after the induction of
      adventitious bud formation in Norway spruce embryos.
AB  - A pulse treatment of embryos of Norway spruce with cytokinin suppresses
      germinative development and induces the coordinate formation of adventitious buds
      from subepidermal cell layers. To analyse the patterns of gene expression
      associated with germination and the alterations induced by the bud induction
      treatment, we have isolated cDNA clones corresponding to genes that are
      differentially expressed in cytokinin-treated and untreated in vitro germinating
      embryos. One category of 14 clones hybridized to transcripts that were abundant
      specifically during germination. The expression of 8 of these genes was reduced
      by the bud induction treatment. Four clones, including one identified as a
      histone H2A gene, recognized transcripts that showed an increased abundance in
      bud-induced versus in vitro germinating embryos. A second category of 13 clones
      hybridized to transcripts that increased in abundance during post-germinative
      development of the seedling. Among these a subset of 8 clones, including an alpha
      tubulin clone, corresponds to genes suppressed by the bud induction treatment,
      whereas 5 clones, including a gene with sequence similarity to polyubiquitin,
      were unaffected by the treatment. One clone hybridized to a message abundant in
      the seed, during early germination as well as in the vegetative bud, and showed
      60% partial sequence identity to a barley (1----3)-beta-glucanase gene. Genes
      expressed exclusively in bud-induced or in vitro germinating embryos were not
      found. The results show that a major difference in gene expression between
      treated and untreated embryos is related to the shift from extensive cell
      proliferation to elongation and differentiation that occurs at the transition
      from germination to post-germinative development, and which is suppressed in the
      bud-induced embryos.

PMID- 1373082
TI  - psaE and trnS(CGA) are encoded on the plastid genome of the red alga Porphyra
      umbilicalis.

PMID- 1373083
TI  - Effect of two consensus sequences preceding the translation initiator codon on
      gene expression in plant protoplasts.
AB  - Expression cassettes containing a duplicated cauliflower mosaic virus (CaMV) 35S
      promoter fused to a polylinker preceded by the CCACCATGG and AACAATGG sequences
      were constructed. These two sequences correspond to the consensus sequences
      around the translation start codons in vertebrates and plants respectively.
      Translational fusions were made with the beta-glucuronidase-coding sequence and
      transient expression was recorded in tobacco mesophyll protoplasts. Approximately
      three times more GUS activity was found in protoplasts incubated with the
      constructs harbouring translational fusions as compared to a control harbouring a
      transcriptional fusion. No significant difference was observed between GUS
      activities obtained with the two consensus sequences.

PMID- 1373084
TI  - Dynamics and localization of early B-lymphocyte precursor cells (pro-B cells) in
      the bone marrow of scid mice.
AB  - Mice homozygous for the scid (severe combined immunodeficiency) mutation are
      generally unable to produce B lymphocytes, a condition attributed to defective
      rearrangement of immunoglobulin genes in precursor B cells. Some early B-lineage
      cells are present in the bone marrow (BM), however. In scid mice, we defined
      three subsets of early progenitor B cells lacking mu heavy chains (pro-B cells)
      based on the expression of terminal deoxynucleotidyl transferase (TdT) and B220
      glycoprotein: (a) early pro-B cells (TdT+B220-), (b) intermediate pro-B cells
      (TdT+B220+), and (c) late pro-B cells (TdT-B220+). Double immunofluorescence
      labeling of BM cell suspensions has shown normal numbers of early and
      intermediate pro-B cells, substantially reduced numbers of late pro-B cells, and
      an absence of pre-B cells and B cells. Early and intermediate pro-B cells
      accumulated in metaphase in near-normal numbers after intraperitoneal (IP)
      vincristine administration. B220+ pro-B cells have been localized in BM sections
      by the binding of intravenously (IV) administered 125I monoclonal antibody (MoAb)
      14.8, detected by light and electron microscope radioautography. Many B220+ cells
      were located peripherally in the bone-lining cell layers associated with stromal
      reticular cells. More centrally located B220+ cells were frequently associated
      with macrophages containing prominent cytoplasmic inclusions. Occasional B220+
      cells were present in venous sinusoids. These results demonstrate that many pro-B
      cells in scid mice occupy microenvironments in the BM near the surrounding bone.
      The pro-B cells maintain normal rates of production during stages of presumptive
      mu heavy-chain gene rearrangement, apparently unaffected by the absence of a
      mature B cell pool. Nearly all defective cells then abort at the late pro-B cell
      stage and are deleted, apparently by macrophages. The findings contribute to
      models of in vivo differentiation, regulation, localization, and selection of
      early B-lineage cells in the BM.

PMID- 1373085
TI  - A unique talin antigenic determinant and anomalous megakaryocyte talin
      distribution associated with abnormal platelet formation in the Wistar Furth rat.
AB  - Rats of the Wistar Furth (WF) strain have hereditary macrothrombocytopenia with
      decreased platelet alpha-granule proteins. The autosomal recessive pattern of
      inheritance of the large mean platelet volume (MPV) phenotype and platelet alpha
      granule protein deficiencies suggest that a component common to both formation of
      platelet alpha-granules and subdivision of megakaryocyte cytoplasm into platelets
      is quantitatively or qualitatively abnormal in WF megakaryocytes and platelets.
      We examined WF platelets for such an abnormality using electrophoretic and
      immunologic analyses. Rabbit antiserum prepared against WF rat platelets and
      absorbed with Wistar rat platelets recognized a major 235-Kd band, and minor
      bands of WF rat platelets ranging from 200 to 130 Kd, not present in immunoblots
      of Wistar, Sprague-Dawley, or Long-Evans rat platelets. The minor bands were
      labeled with affinity-isolated antibody to the 235-Kd band, indicating that all
      bands contained the same unique antigenic site. The 235-Kd antigen had the same
      mobility as rat platelet talin identified with a platelet antitalin antibody.
      Activation of calcium-dependent proteases during Triton X-100 extraction caused
      conversion of the 235-Kd antigen into a major fragment of 200 Kd and minor
      fragments ranging to 115 Kd, identical in mobility to fragments of rat platelet
      talin produced in the same samples. The absorbed anti-WF platelet antiserum also
      detected a 235-Kd antigen in WF lung, kidney, and small intestine by
      immunoblotting. Finally, the 235-Kd antigen unique to WF rats was
      immunoprecipitated from Triton X-100 supernatants of WF platelets with an
      antitalin monoclonal antibody (MoAb). These data indicate that the unique
      antigenic site is on WF talin. Examination of talin distribution in Wistar
      megakaryocytes showed localization beneath the plasma membrane, on the cytosolic
      face of demarcation membranes, associated with alpha-granule membranes, and
      diffusely throughout the cytoplasm. Although WF megakaryocytes showed the same
      general distribution pattern, some differences were apparent. In contrast to
      membrane systems of the Wistar rat, the large membrane complexes in WF
      megakaryocytes contained little or no talin. In addition, approximately half of
      WF megakaryocytes showed an increased peripheral localization of talin, often
      associated with membrane blebs, with decreased talin in the cytoplasmic interior.
      The association of the unique talin antigenic determinant and anomalous
      megakaryocyte talin distribution with abnormal platelet formation in WF rats
      suggests that talin is abnormal in this rat strain and that talin plays an
      important role in subdivision of megakaryocyte cytoplasm into platelets.

PMID- 1373086
TI  - CD4+CD7-CD57+ T cells: a new T-lymphocyte subset expanded during human
      immunodeficiency virus infection.
AB  - CD7 and CD57 are two cell surface molecules related to the differentiation or
      functional stages of CD4+ T cells. The CD4+CD7- T cells represent a minor subset
      of CD4+ cells in normal individuals and are considered to contain the normal
      counterpart of Sezary T cells; the CD4+CD57+ peripheral blood lymphocytes (PBL)
      are detectable in long-term renal allograft recipients. We compared the cell
      surface expression of these CD7 and CD57 markers on CD4+ T lymphocytes in
      peripheral blood and lymphoid organs from normal individuals and human
      immunodeficiency virus (HIV)-infected patients. Our results indicate that CD4+CD7
      T cells in normal PBL do not express CD57 and were poorly responsive to anti-CD3
      monoclonal antibody (MoAb), the activation being restored by addition of anti
      CD28 MoAb. This CD4+CD7- cell subset is increased in peripheral blood during HIV
      infection, and its progressive expansion mirrors both the absolute and relative
      decrease of CD4+ T cells. The lack of CD7 expression is correlated with CD57
      acquisition on CD4+ T cells because CD4+CD7-CD57+ cells represent a major
      component of the CD4+CD7- subset in HIV-infected patients. Our results suggest
      that the presence and the expansion of CD4+CD7-CD57+ T lymphocytes, which do not
      behave as previously defined helper subsets, may participate to the immune
      dysfunction observed during HIV infection.

PMID- 1373087
TI  - Acquired immunodeficiency syndrome-associated T-cell lymphoma: evidence for human
      immunodeficiency virus type 1-associated T-cell transformation.
AB  - The majority of lymphomas in the setting of acquired, iatrogenic, or congenital
      immunodeficiencies are B-cell lymphoproliferations. We describe a rare T-cell
      lymphoma in a fulminantly ill patient infected with human immunodeficiency virus
      type 1 (HIV-1). The T-cell nature of the process was defined genotypically
      (monoclonal T-cell receptor beta-chain [CT beta] rearrangement) and
      phenotypically (CD45RO+, CD4+, CD5+, CD25+, CD8-, CD3- and negative for a variety
      of B-cell and monocyte markers). The CD4+, CD25+ (interleukin-2 receptor [IL-2R])
      phenotype with production of IL-2 and IL-2R RNA is analogous to human T
      lymphotropic virus type I (HTLV-I)-associated adult T-cell leukemia/lymphoma
      (ATLL); however, no HTLV-1 could be detected. Southern blot analysis did
      demonstrate monoclonally integrated HIV-1 within the tumor genome. Furthermore,
      the tumor cells were producing HIV p24 antigen as shown by immunohistochemistry.
      This is the first case of acquired immunodeficiency syndrome (AIDS)-associated
      non-Hodgkin's lymphoma in which HIV-1 infection may have played a central role in
      the lymphocyte transformation process.

PMID- 1373088
TI  - Detection and localization of Epstein-Barr viral genomes in angioimmunoblastic
      lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma.
AB  - We studied 23 cases of angioimmunoblastic lymphadenopathy (AILD) and AILD-like
      lymphoma for evidence of Epstein-Barr virus (EBV) using the polymerase chain
      reaction (PCR) and in situ hybridization studies. EBV nucleic acid sequences were
      found by either PCR or in situ hybridization in 96% of the cases. There was a
      wide range in the number of EBV-positive cells among the different cases as
      detected by in situ hybridization. The EBV-positive cells most often possessed
      nuclei of intermediate to large size. Double-labeling immunohistochemistry/in
      situ hybridization studies demonstrated that most of the EBV-positive cells
      expressed the B-lineage antigen CD20 (as detected by L26), with a minority of the
      EBV-positive cells stained for the T-lineage associated antigen, CD43 (as
      detected by Leu 22). The abnormally high amounts of EBV found in AILD and AILD
      like lymphoma may be a reflection of decreased immunocompetence in these
      patients. The presence of EBV-positive B cells may explain the presence of B-cell
      clones found by others as well as the paradoxical occurrence of B-cell lymphoma
      in a primary T-cell lymphoproliferative disorder.

PMID- 1373090
TI  - Longer in vivo survival of CD59- and decay-accelerating factor-almost normal
      positive and partly positive erythrocytes in paroxysmal nocturnal hemoglobinuria
      as compared with negative erythrocytes: a demonstration by differential
      centrifugation and flow cytometry.
AB  - Three populations of erythrocytes have been shown by flow cytometric analysis on
      complement regulatory proteins: CD59 and decay-accelerating factor (DAF) on
      erythrocytes in paroxysmal nocturnal hemoglobinuria (PNH). CD59 and DAF in PNH
      may be completely deficient in CD59- and DAF-negative erythrocytes, they may be
      decreased varyingly in partly positive erythrocytes, and they may be
      approximately normal in almost normal positive erythrocytes. Control erythrocytes
      are always CD59- and DAF-normal positive. CD59- and DAF-negative erythrocytes
      have been shown to be most sensitive to complement lysis in vitro. However, it
      has not yet been elucidated whether CD59- and DAF-almost normal positive and
      partly positive erythrocytes in a patient have a longer in vivo survival than
      negative erythrocytes. Blood from controls and PNH patients was separated in five
      fractions by differential centrifugation. CD59 and DAF on the fractionated
      erythrocytes were determined by flow cytometry using specific antibodies. Ratios
      of CD59- and DAF-almost normal positive and partly positive cells to negative
      erythrocytes were increased progressively from the top fraction to the bottom.
      The erythrocytes in the top fraction are younger and reticulocyte-rich, while
      those in the bottom are older and reticulocyte-poor. Hence, the present results
      indicate that CD59- and DAF-partly positive erythrocytes as well as almost normal
      positive erythrocytes in patients may have a longer in vivo survival than
      negative erythrocytes.

PMID- 1373089
TI  - Differences in the frequency of normal and clonal precursors of colony-forming
      cells in chronic myelogenous leukemia and acute myelogenous leukemia.
AB  - Acute myelogenous leukemia (AML) is a clonal disease that is heterogeneous with
      respect to the pattern of differentiative expression of the leukemic progenitors.
      In some patients, the involved stem cells manifest pluripotent differentiative
      expression, whereas in others, the involved progenitors manifest differentiative
      expression mainly restricted to the granulocytic pathway. This is in contrast to
      chronic myelogenous leukemia (CML) which is a clonal disease known to arise in a
      pluripotent stem cell. Therefore, we tested whether these leukemias could be
      distinguished with respect to their involvement of immature precursors by
      studying colony-forming cells (CFC) and their precursors from four glucose-6
      phosphate dehydrogenase (G6PD) heterozygous patients with AML and five patients
      with CML. CFC were separated from their precursors by FACS for expression of CD33
      and CD34 followed by growth in a long-term culture (LTC) system. The vast
      majority of CFC express both the CD33 and CD34 antigens, but their less mature
      precursors, detected by their ability to give rise to CFC in LTC, express only
      CD34. In three of the four patients with AML, the CD33-CD34+ cells produced CFC
      in LTC that appeared to be predominantly or completely normal (ie, nonclonal) in
      origin. In the fourth patient, a significant enrichment of nonclonal progenitors
      was obtained in the CD33-CD34+ population, but these cells may also have included
      significant numbers of clonal cells. In contrast, in four of five patients with
      CML, cultures of both the CD33-CD34+ and CD33+CD34+ populations produced CFC in
      LTC that were almost entirely clonal in origin, whereas in the fifth patient a
      substantial number originated from nonclonal stem cells. These data indicate that
      granulocyte/monocyte progenitors are predominantly clonally derived in CML and
      AML. In CML, their precursors are also predominantly clonal, but in some cases of
      AML they are not. These findings may have implications for understanding the
      success or failure of current therapies of AML and CML.

PMID- 1373091
TI  - Influence of steel factor on hemoglobin synthesis in sickle cell disease.
AB  - A new hematopoietic growth factor (Steel factor) has been identified which
      stimulates erythroid proliferation both in vitro and in vivo. We evaluated the
      influence of recombinant Steel factor on hemoglobin synthesis in peripheral blood
      (PB) BFU-E-derived cells from normal donors by radioimmunoassay (RIA) and
      compared it with stimulation with GM-CSF and interleukin-3 (IL-3). Only Steel
      factor stimulated a significant increase in BFU-E-derived colony size and a
      significant increase in fetal hemoglobin (HbF) in BFU-E-derived erythroblasts
      from 0.49% +/- 0.27% to 6.33% +/- 1.11% in serum-deprived media and from 1.88% +/
      0.24% to 11.17% +/- 0.91% in serum. To determine whether this influence on
      hemoglobinization also occurred in sickle cell disease, we studied 13 patients
      with sickle cell disease. In serum-deprived conditions, there was a significant
      increase in the number and size of BFU-E-derived colonies with Steel factor that
      was dose-dependent. In addition, the proportion of HbF in progenitor-derived
      cells increased by 66% from 4.1% +/- 0.6% to 6.8% +/- 1.2% with Steel factor. In
      serum-containing conditions studied in 12 patients, the increase in percentage of
      HbF was even greater, from 10.7% +/- 0.9% in control cultures to 22.5% +/- 2.6%
      with Steel factor. These increases in percentage of HbF were significant and dose
      dependent. An increase in percentage of HbF was observed in erythroblasts
      harvested on day 11, 14, and 18 of culture. A decrease in mean picograms of total
      Hb per cell after coculture with Steel factor was noted, suggesting that growth
      kinetics influenced complete hemoglobinization. In serum-deprived conditions,
      picograms of HbF per cell was not affected by Steel factor, and in serum
      containing conditions that augment in vitro HbF production it was enhanced. Thus,
      Steel factor stimulated a significant increase in percentage of HbF in erythroid
      cells from normal donors and patients with SCA in vitro.

PMID- 1373092
TI  - Circulating granulocyte colony-stimulating factor (G-CSF) levels after allogeneic
      and autologous bone marrow transplantation: endogenous G-CSF production
      correlates with myeloid engraftment.
AB  - Myeloid engraftment after bone marrow transplantation (BMT) is influenced by a
      number of variables, including cytoreductive chemoradiotherapy, genetic
      disparity, number of reinfused committed myeloid progenitor cells, healthy
      microenvironment, and the presence of hematopoietic growth factors. Granulocyte
      colony-stimulating factor (G-CSF) stimulates proliferation of myeloid progenitor
      cells and enhances myeloid engraftment after BMT. We investigated the temporal
      relationship between endogenous G-CSF production and myeloid engraftment in both
      children and adults after allogeneic (ALLO) and autologous (AUTO) BMT.
      Circulating endogenous G-CSF levels ranged between 0 and 2552 pg/mL. The
      correlation coefficient between circulating serum G-CSF levels and the peripheral
      absolute neutrophil count (ANC) was r = -.875 (P less than .001). The endogenous
      serum G-CSF level was highest during the first week after BMT, when the ANC was
      less than or equal to 200/microL (699 +/- 82.3 pg/mL) (P less than .001). Both
      children and adults demonstrated a similar inverse relationship between
      circulating G-CSF level and degree of neutropenia. One patient failed to engraft
      after AUTO BMT and also failed to generate any endogenous G-CSF production.
      Lastly, once the serum G-CSF level decreased to less than 200 pg/mL, a mean of
      6.1 +/- 0.9 days elapsed before the ANC was greater than or equal to 500/microL
      for 2 consecutive days. This study demonstrates that endogenous G-CSF production
      is associated with myeloid engraftment in both children and adults after AUTO and
      ALLO BMT and that the rate of increase and decrease in endogenous G-CSF may be
      predictive of either failure to engraft or duration of neutropenia.

PMID- 1373093
TI  - Characterization of Shiga-like toxin producing Escherichia coli (SLTEC) isolated
      from calves with and without diarrhoea.
AB  - To determine if shiga-like toxin producing Escherichia coli (SLTEC) are involved
      in neonatal calf diarrhoea, isolated E. coli strains from diarrhoeic and non
      diarrhoeic calves were characterized for shiga-like toxin (SLT) by colony blot
      hybridization and cytotoxicity assays. None of 150 E. coli strains isolated from
      diarrhoeic calves in 1985-1988 was positive for SLT, while 7/232 (3.0%) isolated
      in 1989 were positive for SLT. In contrast, samples collected during 1989 and
      1990 from diarrhoeic calves were 21.9% SLTEC positive, and samples from non
      diarrhoeic calves were 12.9% SLTEC positive. SLT I positive E. coli strains were
      isolated more often from diseased (17.8%) than from healthy animals (5.0%), while
      SLT II positive E. coli were more often detected in non-diarrhoeic (8.9%) than in
      diarrhoeic calves (4.1%). The mean percentage of SLT I positive E. coli in the
      whole E. coli flora of the samples was significantly higher in diarrhoeic than in
      healthy animals, implying a pathogenic role of SLT I producing E. coli in
      neonatal calf diarrhoea. Enterohemolysin was produced by 70.8% of the SLT I
      producing E. coli strains examined. Determination of O- and K-antigens of SLT
      positive E. coli revealed a highly diverse spectrum of SLTEC O-groups in calves.
      While no E. coli isolate belonged to serotype O157:H7, classical human
      enteropathogenic E. coli O-groups (O26, O111, O128) were detected. These results
      support the theory that cattle serve as a reservoir for human SLTEC infection.

PMID- 1373094
TI  - Biochemical and serological patterns of Escherichia coli O2 strains isolated from
      patients with urinary tract infections.
AB  - We examined the results of two biochemical test systems for their ability to
      discriminate a series of 58 Escherichia coli O2 strains collected from patients
      with urinary tract infections. The O:K:H serotypes and O antigen factors of the
      strains were also determined. The strains could be assigned to 13 distinct
      serological patterns by means of O2 antigen factors as well as K and H antigens.
      The combination of O:K:H-serotyping with biotyping enabled very fine strain
      discrimination. These data indicate that the biotyping system of Achtman (BTA) is
      more precise than the Enterobacteriaceae-code-system described by Reiske (ECR)
      and that the determination of BTA types supports the identification of bacterial
      clones.

PMID- 1373095
TI  - Inhibition of neurogenic plasma exudation in guinea-pig airways by CP-96,345, a
      new non-peptide NK1 receptor antagonist.
AB  - A new non-peptide tachykinin antagonist, CP-96,345, inhibited airway plasma
      exudation induced in guinea-pigs by i.v. substance P in a dose-dependent manner
      with dose-ratios in the main bronchi of 5 at 1 nmol kg-1 and 19 at 100 nmol kg-1.
      At 100 nmol kg-1, CP-96,345 completely inhibited plasma exudation induced by
      either electrical stimulation of the cervical vagus nerves or i.v. capsaicin,
      indicating inhibition of the effects of endogenous tachykinins, but did not
      inhibit the bronchoconstrictor response to neurokinin A, suggesting selectivity
      for NK1 receptors. CP-96,345 may be useful in examining the role of endogenous
      tachykinins in vivo.

PMID- 1373096
TI  - The effects of chronic treatment with the dihydropyridine, Bay K 8644, on
      hyperexcitability due to ethanol withdrawal, in vivo and in vitro.
AB  - 1. The effects of chronic treatment with the dihydropyridine, Bay K 8644, were
      studied on the ethanol withdrawal syndrome, in vivo and in vitro. 2. Addition of
      racemic Bay K 8644 to the drinking mixture, throughout the chronic ethanol
      treatment, decreased the behavioural excitability seen during ethanol withdrawal
      in vivo. 3. All the signs of hyperexcitability in field potentials in the
      isolated hippocampal slice, caused by ethanol withdrawal, were decreased by the
      chronic administration of Bay K 8644. 4. These effects resembled those previously
      reported for chronic administration of calcium channel antagonists; racemic Bay K
      8644 has both calcium channel activating and antagonist properties. 5.
      Measurement of brain levels of Bay K 8644 at the end of the chronic treatment
      showed that the compound reached micromolar concentrations during the treatment,
      but none could be detected in the tissues at the time of the above measurements.
      6. It is possible that the results might be explained by predominance of the
      calcium channel antagonist properties of this compound, owing to the high central
      concentrations achieved during the treatment. Tolerance to the calcium channel
      activating properties of Bay K 8644 may also have occurred during the chronic
      treatment.

PMID- 1373097
TI  - Effect of dihydropyridines on calcium channels in isolated smooth muscle cells
      from rat vena cava.
AB  - 1. Whole-cell patch-clamp method was applied to single smooth muscle cells
      freshly isolated from the rat inferior vena cava. 2. Depolarizing pulses, applied
      from a holding potential of -90 mV, activated both Na+ and Ca2+ channels. The
      fast Na+ current was inhibited by nanomolar concentrations of tetrodotoxin (TTX).
      The slow Ba2+ current (measured in 5 mM Ba2+ solution) was inhibited by Cd2+ and
      modulated by dihydropyridine derivatives. When the cells were held at a holding
      potential of -80 mV, racemic Bay K 8644 increased the Ba2+ current (ED50 = 10 nM)
      while racemic isradipine inhibited the current (IC50 = 21 nM). 3. The voltage
      dependency of isradipine blockade was assessed by determining the steady-state
      availability of the Ca2+ channels. From the shift of the inactivation curve in
      the presence of isradipine, we calculated a dissociation constant of 1.11 nM for
      inactivated Ca2+ channels. Scatchard plots of the specific binding of (+)-[3H]
      isradipine obtained in intact strips incubated in 5.6 mM or 135 mM K+ solutions
      confirmed the voltage-dependency of isradipine binding. 4. Specific binding of
      (+)-[3H]-isradipine was completely displaced by unlabelled (+/-)-isradipine, with
      an IC50 of 15.1 nM. This value is similar to the IC50 for inhibition of the Ba2+
      current (21 nM) in cells maintained at a holding potential of -80 mV. 5. Bay K
      8644 had no effects on the Ba2+ current kinetics during a depolarizing test
      pulse. The steady-state inactivation-activation curves of Ba2+ current were not
      significantly shifted along the voltage axis.6. The present data suggest the
      existence of two distinct dihydropyridine binding sites which can be bound
      preferentially by agonist or antagonist derivatives.

PMID- 1373098
TI  - M-currents in frog sympathetic ganglion cells: manipulation of membrane
      phosphorylation.
AB  - 1. The inward current and the M-current (IM) suppression produced when muscarine
      is applied to frog sympathetic ganglion cells was recorded by means of the whole
      cell patch-clamp technique. The holding potential was -30 mV and [K+]o was 6 mM.
      2. The steady-state IM was maintained for at least 20 min when the patch pipette
      contained neither adenosine 5'-triphosphate (ATP) nor adenosine 3':5'-cyclic
      monophosphate (cyclic AMP). Inclusion of these substances or the ATP antagonist,
      beta,gamma-methyleneadenosine 5'-triphosphate (beta,gamma-MethATP; 1 or 2 nM)
      (failed to alter the rate of IM 'run down'. By contrast, inclusion of adenosine
      5'-O-(3-thiotriphosphate) (ATP-gamma-S, 1 or 2 mM) resulted in a 60% reduction of
      the current within 18 min. 3. Despite the inability of ATP-gamma-S to maintain
      steady-state IM, it had no effect on the ability of muscarine (2-100 microM) to
      suppress a constant fraction of the available current. ATP-gamma-S and beta,gamma
      MethATP increased the rise time and duration of the response to muscarine. 4.
      Inclusion of a phosphatase inhibitor, diphosphoglyceric acid (DPG, 1-2.5 mM) or
      alkaline phosphatase (100 micrograms ml-1) failed to affect the amplitude of
      muscarinic responses. 5. These results question the role of the phosphorylation
      and/or dephosphorylation reactions in the transduction mechanism for muscarine
      induced IM suppression but are consistent with the possibility that M-channels
      are 'directly coupled' via G-protein to the muscarinic receptor.

PMID- 1373099
TI  - Effects of cromakalim on the contraction and the membrane potential of the
      circular smooth muscle of guinea-pig stomach.
AB  - 1. The effects of cromakalim on mechanical and electrical activities of the
      circular smooth muscles of guinea-pig stomach antrum were observed. 2. Cromakalim
      (greater than 1 x 10(-7) M) decreased the amplitude of spontaneous rhythmic
      contractions and also the acetylcholine-enhanced spontaneous contractions.
      Cromakalim was less effective against the 25.9 mM and 35.9 mM K(+)-induced tonic
      contractions. 3. Glibenclamide (1 x 10(-6) M) itself caused no detectable change
      in the spontaneous contractions, those potentiated by acetylcholine or tonic
      contractions induced by high K+ solutions, but attenuated the actions of
      cromakalim. On the other hand, charybdotoxin (3 x 10(-8) M) increased the
      amplitude of spontaneous contractions but failed to affect the actions of
      cromakalim. 4. Cromakalim (greater than 1 x 10(-6) M) decreased the amplitude and
      duration of slow waves, and hyperpolarized the membrane. These actions of
      cromakalim were completely antagonized by 1 x 10(-6) M glibenclamide, whereas
      part of the effects of cromakalim on mechanical activity was resistant to
      glibenclamide. 5. The results suggest that the inhibition by cromakalim of the
      electrical activity and the hyperpolarization, which may be associated with the
      opening of glibenclamide-sensitive K+ channel, are responsible for its inhibitory
      action on circular smooth muscle of guinea-pig stomach. Further, some effects
      independent of glibenclamide-sensitive K+ channel may also be responsible for the
      mechanical effect.

PMID- 1373100
TI  - Differential inhibitory effects of opioids on cigarette smoke, capsaicin and
      electrically-induced goblet cell secretion in guinea-pig trachea.
AB  - 1. Goblet cell secretion in guinea-pig airways is under neural control. Opioids
      have previously been shown to inhibit neurogenic plasma exudation and
      bronchoconstriction in guinea-pig airways. We have now examined the effects of
      morphine and opioid peptides on tracheal goblet cell secretion induced by either
      electrical stimulation of the cervical vagus nerves, exogenous capsaicin, or
      acute inhalation of cigarette smoke. The degree of goblet cell secretion was
      determined by a morphometric method and expressed as a mucus score which is
      inversely related to mucus discharge. 2. Morphine, 1 mg kg-1, completely blocked
      goblet cell secretion induced by electrical stimulation of the vagus nerves.
      Morphine also inhibited the response to cigarette smoke given either at a low
      dose (10 breaths of 1:10 diluted in air), which principally activates cholinergic
      nerves, or at a high dose (20 breaths of undiluted), which activates capsaicin
      sensitive sensory nerves, by 100% and 73% respectively. In contrast, morphine had
      no significant inhibitory effect on capsaicin-induced goblet cell secretion. The
      inhibitory effect of morphine was reversed by naloxone. 3. Selective mu- or delta
      opioid receptor agonists, [D-Ala2, NMePhe4, Glyol5]enkephalin (DAMGO) or [D-Pen2,
      D-Pen5]enkephalin (DPDPE) respectively, caused a dose-related inhibition of low
      dose cigarette smoke-induced goblet cell discharge, with DPDPE more potent than
      DAMGO. A kappa-receptor agonist, trans-3,4-dichloro-N-methyl-N-(2-(1
      pyrollidinyl)cyclohexyl) benzeneacetamine (U-50,488H), had no inhibitory effect.
      DPDPE had no inhibitory effect on goblet cell secretion induced by exogenous
      methacholine. 4. DAMGO dose-dependently blocked the response to high dose
      cigarette smoke with a maximal inhibition of 95% at 2 x 10(-7) mol kg-1. Neither
      DPDPE nor U-50,488H had any significant inhibitory effect. The increase in goblet
      cell secretion induced by exogenous substance P was not affected by DAMGO.5. We
      conclude that opioids inhibit neurally-mediated goblet cell secretion via actions
      at prejunctional delta and mu-receptors on cholinergic nerves and at mu-receptors
      on sensory nerve endings, and that capsaicin activation of sensory nerves is via
      a different mechanism from that of electrical or cigarette smoke activation.

PMID- 1373101
TI  - An ubiquitous modulating function of rabbit tracheal epithelium: degradation of
      tachykinins.
AB  - 1. To examine the role of epithelium in the responsiveness of tracheal smooth
      muscle in rabbit, we measured the contractile responses to acetylcholine (ACh),
      KCl, 5-hydroxytryptamine (5-HT), histamine, substance P (SP), neurokinin A (NKA),
      and electrical field stimulation  EFS) in intact and epithelium-denuded
      preparations. 2. Removal of epithelium did not alter the contractile response to
      any agonist examined, except SP. 3. Removal of epithelium enhances the
      contractile response to SP. In the presence of phosphoramidon, the contractile
      response to SP was not significantly different in either group. The results
      suggest that the effect of epithelium is largely due to degradation of SP by
      enzymes in the epithelium. 4. Arachidonic acid metabolites did not seem to be
      related to the responses induced by contractile agonists or EFS. 5. In the
      presence of SP, the contractile responses and [3H]-choline outflow evoked by EFS
      were dose-dependently enhanced. Contractile responses to EFS and [3H]-choline
      outflow evoked by EFS were enhanced by SP significantly more than by NKA. Both
      were abolished by atropine or tetrodotoxin. 6. These results suggest that rabbit
      tracheal epithelium may modulate SP-induced contractions, both direct and
      indirect, by inactivation of SP. This phenomenon is widespread in mammals. The
      rabbit may be a useful model to examine airway cholinergic functions.

PMID- 1373102
TI  - Cytoprotection by iloprost against paracetamol-induced toxicity in hamster
      isolated hepatocytes.
AB  - 1 The ability of iloprost (ZK36374) to protect hamster isolated hepatocytes from
      the toxic effects of paracetamol and its reactive metabolite N-acetyl-p
      benzoquinoneimine (NABQI) was investigated. The cytoprotection provided by
      iloprost was compared with that of N-acetyl-L-cysteine. 2 Treatment of
      hepatocytes with either NABQI (0.4 mM) or paracetamol (2 mM) alone resulted in a
      considerable loss of cell viability, as assessed by trypan blue exclusion or
      leakage of lactate dehydrogenase, accompanied by an increase in the percentage of
      viable cells that were blebbed. N-acetyl-L-cysteine (1.25 mM) pretreatment
      diminished the loss of cell viability and the percentage of blebbed cells
      resulting from exposure to NABQI or paracetamol, whereas iloprost (10(-16) M to
      10(-10) M) pretreatment reduced only the loss of cell viability, not the
      percentage of viable cells exhibiting blebbing. Pretreatment with N-acetyl-L
      cysteine significantly attenuated the depletion by paracetamol of glutathione and
      decreased the covalent binding of [14C]-paracetamol to cellular proteins, whereas
      iloprost was without any such effects. 3 The effects of iloprost and N-acetyl-L
      cysteine were also investigated by use of a model of paracetamol toxicity in
      which it is possible to study the biochemical events leading to cell injury
      separate from the generation of toxic metabolites. Hamster hepatocytes were
      incubated with paracetamol (4 mM) for 90 min at 37 degrees C during which
      metabolism of paracetamol occurs with minimal loss of cell viability. Following
      washing of cells, to remove paracetamol and its metabolites, there was a
      progressive loss of viability and increase in the percentage of cells exhibiting
      blebbing when incubated in buffer alone. Addition of either N-acetyl-L-cysteine
      (1.25 mM) or iloprost (10 14M to 10 -M), following washing, significantly reduced
      the expected loss of cell viability. Iloprost at concentrations outside this
      range was without effect.4. Paracetamol toxicity to isolated hepatocytes could be
      prevented or delayed by treatment with either N-acetyl-L-cysteine or iloprost,
      but whereas the former prevented or even reversed plasma membrane blebbing with a
      resultant reduction in the percentage of viable cells that were blebbed, the
      prostanoid appeared only to delay the progression from plasma membrane blebbing
      to loss of viability. Hence, the percentage of viable cells that were ultimately
      blebbed following exposure to paracetamol was not significantly reduced by
      addition of iloprost.5. Aspirin or ibuprofen exacerbated the loss of viability
      induced by prior incubation with paracetamol. Thus, there may be a role for
      endogenous prostaglandins in protecting hepatocytes from paracetamol toxicity.6.
      Iloprost is cytoprotective without any effect upon toxin metabolism or
      detoxication. The mechanism of action of iloprost probably does not involve
      induction of prostaglandin synthesis or activation of the previously
      characterized prostacyclin receptor.

PMID- 1373103
TI  - Different patterns of release of endothelium-derived relaxing factor and
      prostacyclin.
AB  - 1. Release of endothelium derived relaxing factor (EDRF) and prostacyclin (PGI2)
      from endothelial cells (EC) cultured from bovine aortae was measured by bioassay
      and radioimmunoassay, respectively, during infusions (10 min) of bradykinin (BK),
      adenosine diphosphate (ADP), arachidonic acid (AA), alkaline buffers and the free
      bases (FB) of L-arginine or D-arginine. Release of EDRF from the luminally
      perfused rabbit aorta was also measured during infusions (10 min) of
      acetylcholine (ACh), substance P and ADP. 2. Bradykinin (10 or 30 nM) infused
      through the column of EC induced release of both EDRF and PGI2, neither of which
      was maintained for the duration of the infusion. 3. ADP (1.6 or 4 microM) infused
      through the column of EC induced release of a EDRF which was maintained for the
      duration of the infusion and a release of PGI2 which lasted for a much shorter
      period. 4. Arachidonic acid (30 or 90 microM) infused through the column of EC
      caused a sustained release of EDRF and PGI2, both of which outlasted the infusion
      of AA. 5. L-Arginine FB, D-arginine FB or alkaline buffer infused through the
      column of EC released EDRF, but only small amounts of PGI2. The release of EDRF
      outlasted the period of infusion and was due to an increase in the pH of the
      Krebs solution perfusing the EC. 6. Infusions of ACh (0.25-1 microM) or ADP (4-16
      microM) caused a sustained release of EDRF from the luminally-perfused rabbit
      aorta, whereas infusion of substance P (3.3-10 microM) caused only a transient
      release of EDRF. 7. These results show that distinct patterns of EDRF release
      exist to different agonists in both cultured and in situ EC, and that EDRF and
      PGI2 do not necessarily follow the same time course of release. Furthermore,
      sustained release of EDRF does not require the constant infusion of the
      precursor, L-arginine, whereas sustained release of PGI2 only occurs when AA, the
      precursor of PGI2, is present in the extracellular medium.

PMID- 1373104
TI  - Mechanical restitution and post extrasystolic potentiation of perfused rat heart:
      quantitative comparison of normal right and left ventricular responses.
AB  - Interval-force relationship of right and left ventricles of the isolated perfused
      rat heart was quantified by fitting polynomial, linear and mixed linear
      exponential functions to the mechanical restitution (MRC) and post extrasystolic
      potentiation (PESPC) curves. Ventricular maximum developed pressure (Pmax) and
      its first derivative (dP/dtmax) were used as indices of contractility. MRCs and
      PESPCs could be separated into two distinct phases: phase A and phase B of MRCs;
      phase I and phase II of PESPCs. These phases for the right and left ventricle of
      the rat heart could be explained on the same model of cellular kinetics of the
      activator calcium, but showed distinct differences from other species. Right and
      left ventricle inotropic reserve (CRmax), as quantified from the centre of mass
      of the phase B of MRCs (from normalized Pmax), was (mean +/- SE): 132.4 +/- 2.05%
      and 132.1 +/- 1.7% at 1 Hz, which increased significantly (P less than 0.001) to
      181.0 +/- 5.8% and 182.3 +/- 5.2% at 3.3 Hz, respectively. Linear regression of
      normalized right ventricle extrasystolic responses on the left ventricle
      responses gave a high correlation coefficient (typically r2 = 0.97). Time
      constants of the fitted mechanical restitution (TMRC) and post extrasystolic
      potentiation (TPESPC) curves were at 1 Hz, TMRC and TPESPC (from normalized
      dP/dtmax) were (mean +/- SE): 161.6 +/- 10.8 and 159.0 +/- 13.2 ms for right
      ventricle, and 196.1 +/- 14.5 and 188.3 +/- 10.7 ms for left ventricle,
      respectively. The results of this study indicate that interval-force relationship
      of the rat heart, as exemplified by CRmax and time constants of the fitted
      curves, could provide a useful index for quantifying and comparing right and left
      ventricular functions.

PMID- 1373105
TI  - Synergistic cytotoxicity with 2'-deoxy-5-azacytidine and topotecan in vitro and
      in vivo.
AB  - Synergy, when it can be convincingly established, is an effective strategy for
      the development of novel drug combinations. We have evaluated the interaction
      between 2'-deoxy-5-azacytidine (DAC) and 9-dimethylaminomethyl-10
      hydroxycamptothecin (topotecan) based on our hypothesis that DAC, through DNA
      hypomethylation, might increase the transcription of topoisomerase I (topo I)
      leading to increased sensitivity to topotecan. Five human tumor cell lines, A375
      melanoma, DX-3 melanoma, DMS4C non-small cell lung carcinoma, UP-1 unknown
      primary adenocarcinoma, SN12C renal carcinoma, and the murine CT-26 tumor cell
      line, were studied. Drug interactions were assessed using the multiple drug
      effect analysis of Chou and Talalay (Chors, T-C, and Talalay, P. Adv. Enzyme
      Regul., 22:27-54, 1984.). A synergistic interaction was documented in four human
      cell lines and the murine CT-26 line. An antagonistic interaction was observed
      with the SN12C cell line. The toxicology and efficacy of this combination were
      analyzed using CT-26 in BALB/c mice. Various treatment schedules were studied,
      including: single doses of each agent; single sequential combination treatments
      where DAC was administered followed by topotecan 24 h later; and multiple
      sequential treatments where DAC and topotecan were administered on days 1, 2, 8,
      and 9. Efficacy studies showed that the single sequential combination of DAC (50
      mg/kg) and topotecan (10 mg/kg) resulted in tumor growth delay as compared to
      single doses of DAC (50 mg/kg) or topotecan (10 mg/kg). When the multiple
      sequential combination schedule was used, the antitumor effect was more
      pronounced. In that experiment 50% of the control animals had tumors of 20 mm by
      day 28. For animals receiving a single sequential treatment with DAC and
      topotecan, the median time until the mean tumor size reached 20 mm was 38 days,
      and for the group with multiple sequential combination treatments the time was 51
      days. Studies of the mechanism of the interaction showed that the activity of
      topotecan versus each cell line correlated with the topo I activity in nuclear
      extracts However, there was no correlation between topo I levels and synergy and
      no reproducible increase in topo I activity following exposure to DAC. Thus,
      while the exact mechanism of the interaction remains unclear, DAC can be
      effectively combined with topotecan to enhance antitumor activity.

PMID- 1373106
TI  - Synergy of interleukin 3 and tumor necrosis factor alpha in stimulating clonal
      growth of acute myelogenous leukemia blasts is the result of induction of
      secondary hematopoietic cytokines by tumor necrosis factor alpha.
AB  - Colony growth of leukemic colony-forming units (L-CFU) obtained from patients
      with primary acute myelogenous leukemia stimulated with recombinant human
      interleukin 3 (rh IL-3) is significantly potentiated when recombinant human tumor
      necrosis factor alpha (rh TNF-alpha) is present in cultures. The costimulatory
      activity of tumor necrosis factor (TNF) alpha is dose dependent and maximum at
      TNF-alpha concentrations of 10 ng/ml. At high density, L-CFU proliferatively
      respond to TNF-alpha stimulation in the absence of exogenous rh IL-3. Studies of
      the mechanism of action of rh TNF-alpha on acute myelogenous leukemia L-CFU
      growth suggest that TNF-alpha acts by inducing release of growth stimulatory
      hematopoietic cytokines by the leukemic cells themselves, including IL-1 alpha,
      IL-1 beta, Granulocyte-macrophage colony-stimulating factor (CSF), granulocyte
      CSF, and IL-6. Treatment of L-CFU cultures, with neutralizing antibodies to IL-1
      alpha, IL-1 beta, granulocyte-macrophage CSF, granulocyte CSF, and IL-6 to
      eliminate the endogenous source of these factors is associated with significant
      inhibition of the synergistic interplay of TNF-alpha and IL-3.

PMID- 1373107
TI  - Up-regulated biosynthesis and expression of endothelial cell vitronectin receptor
      enhances cancer cell adhesion.
AB  - Extravasation of circulating cancer cells during metastasis is thought to involve
      adhesion to the vascular endothelium. To characterize this process, we measured
      the attachment of A549 human lung carcinoma cells to monolayers of cultured human
      umbilical vein endothelial cells. Pretreatment of the endothelial cells with 10
      ng/ml interleukin 1 alpha (IL-1) for 4 h increased cancer cell attachment 2-5
      fold. This increase was blocked by 100 microM glycyl-arginyl-glycyl-aspartyl
      serine peptide and was decreased 60 +/- 10% (SD) by a vitronectin receptor
      polyclonal antiserum or 56 +/- 8% by a vitronectin receptor monoclonal antibody,
      LM609. Glycyl-arginyl-glycyl-aspartyl-serine or the vitronectin receptor
      antibodies did not inhibit cancer cell attachment to untreated endothelial cells.
      A fibronectin receptor antiserum had no effect on attachment to untreated or IL-1
      treated endothelial cells. Pretreatment of endothelial cells with IL-1 increased
      their adhesion to fibronectin and vitronectin and increased the expression of
      vitronectin receptor and fibronectin receptor as detected by immunofluorescence
      flow cytometry, quantitative antibody binding, and immunoprecipitation of
      [35S]methionine-labeled cell extracts. IL-1 pretreatment also increased beta 1,
      beta 3, and alpha, integrin mRNA. The A549 cells did not express vitronectin
      receptor, since LM609 did not inhibit A549 adhesion to vitronectin or bind to
      A549 cells in flow cytometry, and vitronectin receptor antisera failed to
      immunoprecipitate vitronectin receptor from A549 cells. Furthermore, the beta 3
      complementary DNA probe failed to hybridize to A549 RNA. A549 cells did express
      fibronectin receptor, which was increased by IL-1 treatment. We conclude that IL
      1 induces the expression of both vitronectin receptor and fibronectin receptor on
      endothelial cells and that vitronectin receptor, in turn, facilitates A549 cell
      adhesion to endothelial cells.

PMID- 1373108
TI  - Second generation anti-MUC1 peptide monoclonal antibodies.
AB  - Second generation antibodies to mammary mucins were produced by immunizing mice
      with a peptide with a sequence deduced from that of the MUC1 complementary DNA
      sequence (PAHGVTSAPDTRPAPGSTAP). Four monoclonal antibodies (BCP7-10) were
      produced which gave different reactions. BCP8 was similar in tissue reactivity
      (by immunoperoxidase staining) to anti-breast cancer or anti-human milk fat
      globule membranes (HMFG) antibodies and reacted strongly with most breast cancers
      and a proportion of other adenocarcinomas, whether formalin fixed or fresh, and
      reacted less strongly with some normal tissues. The three other antibodies (BCP7,
      BCP9, BCP10) reacted only with fresh tissues or a single cell line (LS174T of
      colon cancer origin) and gave variable weak reactions. Like many anti-mucin
      antibodies BCP8 reacted with HMFG, but more strongly with deglycosylated HMFG;
      analysis with peptides by enzyme-linked immunosorbent assay indicated reactivity
      with an epitope contained in the amino acid motif PDTR and using the pepscan
      method, the minimum epitope was DTR. MAbs BCP7, BCP9, and BCP10 did not react
      with HMFG; substantial reactions were obtained with deglycosylated HMFG for BCP7
      and weaker reactions with BCP9 and BCP10. The finding that BCP7 reacted with
      breast cancer tissues and deglycosylated HMFG suggested that the epitope
      recognized by BCP7 was masked in native form and exposed in cancer, indicating
      that BCP7 could be a useful agent for analyzing differences between normal and
      cancer mucins. The amino acid epitopes for these antibodies were VTSA (BCP7),
      GSTAP (BCP9), and RPAP (BCP10). For BCP8, amino acid substitution analysis of
      SAPDTR indicated that substitutions were poorly tolerated (except Q for T and L/Y
      for R), contrasting with the substitution analysis of anti-mucin antibody
      reactions where virtually any amino acid can be substituted for T, indicating
      that in the native state T (threonine) may be O-glycosylated. The use of
      synthetic peptides to produce antibodies similar to those produced using crude
      mucins or tumor extracts represents a major advance in the production of
      antitumor reagents.

PMID- 1373109
TI  - Cyclooxygenase inhibitors modify the relaxant effect of vasoactive intestinal
      polypeptide and substance P in isolated porcine ophthalmic artery.
AB  - The absolute indomethacin effect in some unilateral headaches may, at least
      partially, be cyclooxygenase inhibition-independent. Aspirin and indomethacin,
      for example, may inhibit the neurogenically induced plasma extravasation in rat
      dura mater. Given the putative involvement of trigeminal neuropeptides in the
      pathophysiology of these conditions, the influence of cyclooxygenase inhibitors
      (indomethacin, acetylsalicylic acid (ASA) and naproxen) has been studied upon
      substance P, calcitonin gene-related peptide and vasoactive intestinal peptide
      (VIP)-induced vasodilatation in PGF2 alpha precontracted porcine ophthalmic
      arteries in vitro. None of the cyclooxygenase inhibitors significantly altered
      the effects of calcitonin gene-related peptide. The 10(-10) mol/l VIP-induced
      relaxation was inhibited significantly by all three cyclooxygenase inhibitors.
      Substance P-induced relaxation (from 10(-10) to 10(-8) mol/l) was enhanced by ASA
      and inhibited both by naproxen and, to a lesser extent, by indomethacin. The
      results suggest mainly that VIP-induced relaxations, particularly at lower
      concentrations, may be inhibited by all three cyclooxygenase inhibitors, and that
      naproxen, to a greater extent than aspirin or indomethacin, showed a tendency to
      inhibit vasodilatation induced by all peptides.

PMID- 1373110
TI  - The role of beta 1 integrin in spreading and myofibrillogenesis in neonatal rat
      cardiomyocytes in vitro.
AB  - The influence of the extracellular matrix (ECM) on cell behavior,
      myofibrillogenesis and cytoarchitecture was investigated in neonatal rat cardiac
      myocytes in vitro. Cell behavior was examined by analyzing cell spreading on
      different ECM components under a variety of experimental conditions. Area
      measurements were made on digitized images of cells grown for various time
      intervals on fibronectin (FN), laminin (LN), collagens I and III (C I+III),
      plastic, and bovine serum albumin (BSA). The amount of spreading was varied on
      the different matrices and was maximal on FN greater than LN greater than C I+III
      greater than plastic greater than BSA. Addition of anti-beta 1 integrin
      antibodies to myocytes cultured on FN, LN and C I+III blocked spreading outward
      on the substrates and altered normal myofibrillogenesis, especially on LN.
      Concomitantly, the integrin antibodies induced the formation of giant
      pseudopodial processes which protruded upward from the substrates. These
      pseudopods contained actin polygonal networks which exhibited a regular
      geometrical configuration. Effects of the ECM on cytoarchitecture was examined by
      analyzing the temporal and spatial patterns of fluorescence and immunogold
      labeling of cytoskeletal and integrin proteins as myocytes spread in culture. The
      first indication of sarcomeric patterns was the appearance at 4 hours of
      striations formed by lateral alignment of alpha-actinin aggregates into Z bands.
      At later times, vinculin at 8 hours and beta 1 integrin at 22 hours became co
      localized with alpha-actinin at the Z bands and focal adhesions. These data
      indicate that ECM components influence myocyte spreading and that myofibril
      assembly and/or stability is associated with ECM-integrin-cytoskeleton
      associations.

PMID- 1373111
TI  - Effects of steroid hormones and related compounds on gene transcription.

PMID- 1373112
TI  - Detection of occult metastatic lobular carcinoma in axillary lymph nodes using
      anticytokeratin monoclonal antibodies.
AB  - To examine the importance of immunocytochemically detectable occult axillary
      lymph node metastases in patients with lobular carcinoma of breast, tumor
      registry data from 54 cases indexed as lobular carcinoma during the period 1973
      82 were reviewed. Recurrences and/or deaths due to cancer were essentially
      confined to the group of patients with a component of invasive lobular carcinoma
      (ILC), therefore this subset was selected for further study. Seven of 20 cases
      had lymph node metastases diagnosed histologically at the time of mastectomy.
      Follow-up of these patients showed four dead of disease (DOD) at one, three,
      three, and seven years; one alive with disease (AWD) at one year; and two with no
      evidence of disease (NED) at four and five years. Eleven of 20 were node
      negative. Follow-up of this group showed nine NED and two DOD at two and four
      years. Two of 20 had unknown node status. Formalin-fixed, paraffin embedded lymph
      node blocks were available in 12 of 20 cases with a component of ILC. Of these,
      4/12 cases had histologically positive nodes while 8/12 were originally diagnosed
      as negative. A cytokeratin monoclonal antibody cocktail (MAK-6, CAM 5.2 and
      AE1/AE3) was applied to all 12 cases. Cytokeratin immunoreactivity (CK-IR) was
      found in all four cases that were histologically positive. Five of eight
      histologically negative nodes lacked CK-IR, however the other three cases showed
      CK-IR in micrometastases. Review of newly prepared hematoxylin-eosin sections
      from the paraffin blocks failed to demonstrate metastases.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1373113
TI  - [The palliative treatment of primary hepatocellular carcinoma by
      chemoembolization].
AB  - 16 patients (12 men, 4 women; mean age 62.8 +/- 9.8 years) with inoperable
      advanced hepatocellular carcinoma were treated palliatively by chemoembolization.
      50 mg/m2 epirubicin, 30 mg/m2 cisplatin, 8 ml fatty acid ethyl ester of iodinated
      papaver oil and 10 ml nonionic contrast medium were injected under fluoroscopy
      into the proper hepatic artery. Partial remission was achieved in 10 patients
      after a median of 4 months. In 4 patients there was no change in the
      morphological and biochemical findings, in two others the tumour progressed, i.e.
      an overall response rate of 62.5%. The median survival time was 9 months. There
      were no serious complications ascribable to the treatment. Chemoembolization is a
      palliative treatment with few side effects which can also be effective in
      prolonging survival time in advanced hepatocellular carcinoma.

PMID- 1373114
TI  - Endoscopic therapy of esophago-gastric tumors.

PMID- 1373115
TI  - Ionic permeability of the mitochondrial outer membrane.
AB  - The ionic permeability of the outer mitochondrial membrane (OMM) was studied with
      the patch clamp technique. Electrical recording of intact mitochondria (hence of
      the outer membrane (OM], derived from mouse liver, showed the presence of
      currents corresponding to low conductances (less than 50 pS), as well as of four
      distinct conductances of 99 pS, 152 pS, 220 pS and 307 pS (in 150 mM KCl). The
      latter were voltage gated, being open preferentially at positive (pipette)
      potentials. Very similar currents were found by patch clamping liposomes
      containing the isolated OM derived from rat brain mitochondria. Here a
      conductance of approximately 530 pS, resembling in its electrical characteristics
      a conductance already attributed to mitochondrial contact sites (Moran et al.
      1990), was also detected. Immunoblot assays of mitochondria and of the isolated
      OM with antibodies against the outer membrane voltage-dependent anion channel
      (VDAC) (Colombini 1979), showed the presence of the anion channel in each case.
      However, the typical electrical behaviour displayed by such a channel in planar
      bilayers could not be detected under our experimental conditions. From this
      study, the permeability of the OMM appears different from what has been reported
      hitherto, yet is more in line with that multifarious and dynamic structure which
      apparently should belong to it, at least within the framework of mitochondrial
      biogenesis (Pfanner and Neupert 1990).

PMID- 1373116
TI  - Behavioral effects of concurrent lesions of the nucleus basalis magnocellularis
      and the dorsal noradrenergic bundle.
AB  - The effects of separate and concurrent lesions to the cholinergic and
      noradrenergic (NE) systems were assessed in two water mazes. Lesion of the
      nucleus basalis magnocellularis (NBM) decreased performance in a spatial memory
      task (Morris water maze) while lesions of the dorsal NE bundle (DNB) enhanced the
      acquisition of this task independent of the NBM effects. Both lesions impaired
      performance on a water-escape motivated T-maze; however, the deficits induced by
      the combined lesion did not differ from the effects of either lesion alone.
      Neither lesion, nor their combination, had significant effects on open field
      activity. Biochemical analyses revealed almost total loss of NE in the cortex and
      hippocampus after DNB lesion, with relatively minor changes in other
      catecholamines or metabolites. Choline acetyltransferase activity was not
      significantly altered by the DNB lesion but was decreased in the cortex by the
      NBM lesion. These results suggest a task-specific effect of DNB lesion that is
      detectable under conditions of mild stress when floor effects are minimized.

PMID- 1373117
TI  - Antisense CCAAT/enhancer-binding protein RNA suppresses coordinate gene
      expression and triglyceride accumulation during differentiation of 3T3-L1
      preadipocytes.
AB  - Previous studies suggest that the CCAAT/enhancer-binding protein (C/EBP)
      functions in the coordinate expression of adipocyte genes during differentiation
      of 3T3-L1 preadipocytes. We sought to block expression of C/EBP selectively using
      a bovine papilloma virus (BPV) vector to direct transcription of a approximately
      0.4-kb segment of C/EBP cDNA (in antisense orientation) containing translated
      sequence 5' to that encoding the basic and leucine zipper regions of the protein.
      Vector-directed expression of antisense C/EBP RNA in 3T3-L1 preadipocytes
      inhibited expression of C/EBP mRNA and protein, as well as several adipose
      specific mRNAs, and also prevented cytoplasmic triglyceride accumulation. Rescue
      of the "adipocyte phenotype" was accomplished by transfection of cells expressing
      antisense RNA with a modified BPV vector that directs transcription of the
      complementary sense C/EBP RNA.

PMID- 1373118
TI  - Transformation by FosB requires a trans-activation domain missing in FosB2 that
      can be substituted by heterologous activation domains.
AB  - Two functionally distinct proteins derived from the FosB gene by alternative
      splicing have recently been described. FosB protein transforms fibroblasts
      efficiently, whereas FosB2 protein, a carboxy-terminally truncated form of FosB,
      does not, despite the fact that both proteins can participate in high-affinity,
      sequence-specific DNA binding as part of a heterodimeric complex with c-Jun
      protein. We show here that the functional difference between these proteins is
      the result of the presence of a potent proline-rich transcriptional activation
      domain in the carboxy-terminal amino acids unique to FosB. This conclusion is
      supported by three lines of evidence: (1) Mutations in the carboxy-terminal
      region of FosB that impair transcriptional activation also reduce transforming
      potential, despite the fact that DNA binding as part of a complex with c-Jun is
      not affected; (2) the carboxy-terminal region unique to FosB functions as an
      activation domain when fused to the DNA-binding domain of GAL4; and (3)
      transforming potential can be conferred on FosB2 by fusing any of several
      different well-characterized trans-activation domains. These results identify an
      additional functional requirement for transformation by Fos proteins and have
      implications for the mechanism(s) of mitogenic signaling by the AP-1
      transcription complex.

PMID- 1373119
TI  - Cluster of fibronectin type III repeats found in the human major
      histocompatibility complex class III region shows the highest homology with the
      repeats in an extracellular matrix protein, tenascin.
AB  - Walking and sequencing a genome portion centromeric of CYP21B in the human MHC
      class III region disclosed a cluster of fibronectin type III repeats in an
      approximately 50-kb DNA segment. Fibronectin type III repeats are known to
      consist of ca. 90 amino acid residues and exist in a wide range of protein
      species. Homology searches in protein databases showed that the repeats found had
      the highest homology with the repeats of human tenascin, an extracellular matrix
      protein. One cDNA sequence located immediately centromeric of CYP21B, the 3'
      portion of which is transcribed by the opposite strand of CYP21B, was found also
      to have six type III repeats followed by a fibrinogen domain. Pairwise homology
      comparison of these repeats in the MHC locus with those of human tenascin showed
      a general parallelism in their gene organization, indicating that the newly found
      repeats are elements of certain tenascin-like genea.

PMID- 1373120
TI  - Contiguous localization of the genes encoding human insulin-like growth factor
      binding proteins 1 (IGBP1) and 3 (IGBP3) on chromosome 7.
AB  - In extracellular fluids the insulin-like growth factors (IGFs) are bound to
      specific binding proteins (IGBPs). The genes for two members of this protein
      family have been mapped, the IGBP1 gene to human chromosomal region 7p14-p12 and
      the IGBP2 gene to region 2q33-q34. In this study, somatic cell hybrid analysis
      indicated that IGBP3 is also located on chromosome 7. Pulsed-field gel
      electrophoresis was used to demonstrate the close physical linkage between IGBP1
      and IGBP3. Overlapping cosmid clones encompassing these genes were isolated, and
      restriction endonuclease mapping showed that the genes are arranged in a tail-to
      tail fashion separated by 20 kb of DNA. Further characterization of the IGBP1 DNA
      sequence disclosed a duplication of the intron 3-exon 4 junction within the third
      intron. In addition, we report RFLPs for ApaLI and TaqI in the IGBP1 locus.

PMID- 1373121
TI  - Sequence organization of variant mouse 4.5 S RNA genes and pseudogenes.
AB  - The rodent 4.5 S RNA is an RNA polymerase III product with a sequence related to
      the Alu family of interspersed repeated DNA. A previous study identified a tandem
      array of 4.2-kb repeating units that contain the 4.5 S RNA coding sequence as
      well as many short repetitive sequences. To understand the genomic organization
      of this gene family, we have isolated and characterized 4.5 S RNA sequences that
      are part of the tandem array as well as identified members that are not part of
      the array. One variant 4.5 S RNA gene family member exhibits length polymorphisms
      in its minisatellite sites relative to the single previously reported gene. The
      4.5 S RNA sequences that are not part of the tandem array possess many of the
      features of processed pseudogenes and are found adjacent to other interspersed
      repeated elements. These findings suggest that the mouse 4.5 S RNA can behave as
      a retroposon, resulting in the accumulation of 4.5 S RNA-like elements at many
      sites in the genome.

PMID- 1373122
TI  - Characterization of two missense mutations in human galactose-1-phosphate
      uridyltransferase: different molecular mechanisms for galactosemia.
AB  - We report the molecular characterization of two novel galactosemia mutations that
      exhibit different molecular phenotypes. Both are of the missense type with low or
      no residual enzyme activity. The R148W mutation results in an unstable protein,
      although messenger RNA is still produced. In contrast, the L195P mutation
      produces stable but inactive immunoreactive protein. The R148W mutation alters an
      amino acid that is not evolutionarily conserved, while the L195P mutation affects
      a well-conserved residue nine amino acids down-stream from the putative active
      site nucleophile. These mutations provide evidence that different mechanisms can
      result in galactosemia: destabilizing mutations in any given area of the protein
      and missense mutations in conserved domains of the enzyme resulting in low or no
      activity. These two mutant alleles represent the fifth and sixth galactosemia
      mutations and confirm the hypothesis that galactosemia results from a
      multiplicity of mutations at the molecular level.

PMID- 1373123
TI  - Acute optic neuritis associated with immunization with the CNS myelin proteolipid
      protein.
AB  - Optic nerve tissue for SJL/J mice immunized with the central nervous system (CNS)
      myelin-specific proteolipid protein (PLP) was examined for histopathologic
      evidence of optic neuritis. Optic nerves isolated 17 d after immunization with
      PLP revealed an interstitial and submeningeal inflammatory infiltrate consisting
      of neutrophils and monocytes. In all cases, histologic evidence of optic nerve
      involvement correlated serologically with the presence of circulating anti-PLP
      antibodies. Control animals had no histopathologic evidence of disease or anti
      PLP antibody. In many respects, the observed histopathologic profile of PLP
      induced optic neuritis is similar to that associated with human inflammatory
      demyelinating diseases such as multiple sclerosis (MS). Because optic neuritis
      frequently is associated with some of the earliest clinical symptoms of MS, the
      acute nature of optic nerve involvement in this animal model suggests that immune
      recognition of the myelin PLP may play a significant role in the pathophysiology
      of optic nerve damage associated with sensitization to CNS-specific antigens.

PMID- 1373124
TI  - An experimental model of ectropion uveae and iris neovascularization in the cat.
AB  - Neovascularization of the iris (NVI) is one of the most frequently studied
      intraocular vascular proliferations in animal models. Ectropion uveae has not
      been a consistent finding in these studies. In this study, a surgical model of
      ectropion uveae and iris neovascularization was developed that involved
      lensectomy, vitrectomy, bipolar cautery and transection of all three principal
      branch veins in the cat eye. Twelve of 14 eyes that received this procedure
      developed postoperative retinal detachments with a clinical picture of
      hemorrhagic retinopathy. These eyes progressed to a clinical picture of NVI
      within 1-7 wk. Eight eyes developed ectropion uveae for as much as 300 degrees.
      At the light microscopic level, a fibrovascular membrane was apparent on the
      anterior iris stroma in 9 of 14 eyes and further involved the angle in six eyes.

PMID- 1373125
TI  - Analysis of the autoimmune infiltrate in experimental encephalomyelitis.

PMID- 1373126
TI  - Effect of traumatic occlusion on CGRP and SP immunoreactive nerve fibre
      morphology in rat molar pulp and periodontium.
AB  - Traumatic occlusion provides a trauma that affects the whole tooth and its
      supporting tissues. To study the effect of this trauma on CGRP and SP
      immunoreactive nerve morphology in pulp and periodontium, traumatic occlusion was
      induced in 2-months-old rats. The occlusal surface of the first maxillary molar
      in 30 rats were unilaterally raised 1 mm with a composite material. At different
      observation periods up to 30 days, the rats were transcardiacally perfused, the
      jaws demineralized, sectioned and processed for immunohistochemistry with the
      avidin-biotin-peroxidase method. Changes in nerve morphology, distribution and
      density in first and second molars and their supporting tissues were analyzed and
      compared in experimental (n = 30) and control rats (n = 14). Already after 5 days
      with traumatic occlusion, 22% of the experimental teeth had increased density of
      CGRP and SP immunoreactive nerves locally in gingiva, the periodontal ligament
      and the pulp, while in 15%, axonal proliferation and changed nerve morphology
      were found in the whole pulp (severe reaction). During a 20-day period, the
      pulpal nerve reactions progressed and included the whole pulp in 46% of the
      experimental teeth. The periodontal nerve responses were still localized only to
      the cervical and apical regions, and they remained local in these areas
      throughout the experimental periods. After 20 days the number of teeth with
      severe nerve changes seemed to decrease. The study shows that an unilateral
      change in occlusion of the first molar initiate nerve responses in the total
      molar dentition. In this experimental model the pulpal axons containing CGRP and
      SP reacted more serious to occlusal trauma than the nerves in the periodontium.
      The results indicate that the nerve changes in some cases might be transient.

PMID- 1373127
TI  - Production of monomeric antigen-enzyme conjugate to study requirements for
      follicular immune complex trapping.
AB  - Studies concerning the localization of immune complexes in lymphoid follicles and
      the involvement of these trapped immune complexes in the regulation of the immune
      response have thus far been performed with poorly defined complexes in terms of
      size and composition. For that reason, the minimum requirements for trapping in
      terms of number of antigen- and antibody molecules present in immune complexes
      could not be determined. We here describe the production and in vivo use of a
      monomeric HSA-HRP antigen-enzyme conjugate, readily demonstrable in cryostat
      sections and ELISA. This conjugate was obtained by combining the glutaraldehyde
      coupling-method with chromatography to fractionate monomeric and multimeric
      constituents. SDS-PAGE analysis showed that the conjugate consisted of a single
      molecular species of 109 kDa, whereas the often used periodate oxidation coupling
      method yielded a heterogeneous population of multimeric, oligomeric and monomeric
      molecules. We investigated the minimal size requirements for the composition of
      immune complexes to be trapped in murine spleen follicles using three different
      conjugates (monomeric HSA-HRP, multimeric HSA-HRP and multimeric HSA-HRP
      Penicillin) and a panel of anti-HSA and anti-Penicillin monoclonal antibodies. We
      demonstrate that the smallest immune complexes, consisting of one antibody and
      two conjugate molecules, do not localize in splenic follicles. Immune complexes
      prepared with a single monoclonal antibody localize in follicles only if the
      epitope recognized occurs repeatedly on the antigen. The relevance of these
      results for physiological follicular trapping of protein antigens is
      discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373128
TI  - Effects of tissue processing techniques in acoustical (1.2 GHz) and light
      microscopy.
AB  - In this study the influence of various tissue processing and staining techniques
      on the acoustical properties of liver tissue was investigated. A qualitative
      study was performed using ultrasound attenuation as the imaged parameter of a
      combined optical/acoustical microscope with a 1.2 GHz transducer. Images were
      made of three sets of adjacent liver sections (6 microns in thickness) which were
      prepared in ten different ways: fixed by alcohol or formalin; stained by
      hematoxylin-eosin (HE), toluidine blue (TB) or non-stained; sectioned by a
      cryostat or by a paraffin microtome. It was concluded that the images obtained
      from cryostat sections were of much higher quality than those from paraffin
      sections. Images obtained from sections that were sectioned while embedded in
      paraffin displayed no detail at all. No consistent effect was noticed with
      respect to staining by HE or TB. Alcohol fixed sections gave more detailed images
      than formalin fixed sections. Formalin fixation in combination with cryostat
      sectioning yielded many cytoplasmic vacuoles.

PMID- 1373129
TI  - Multicentric osseous lymphoma with spinal extradural involvement in a dog.
AB  - Multicentric osseous lymphoma involving the ribs and multiple vertebrae was
      observed in a 7-year-old Siberian Husky. Extradural spinal cord compression was
      treated by surgical decompressive hemilaminectomy of L1-2 without noticeable
      improvement of signs neurologic dysfunction. However, palliation of signs of pain
      was noticed after irradiation in conjunction with chemotherapy and surgical
      decompression.

PMID- 1373130
TI  - Viral infection increases contractile but not secretory responses to substance P
      in ferret trachea.
AB  - Viral infection increases the airway smooth muscle response to substance P. This
      effect is due to decreased activity of neutral endopeptidase (EC 3.4.24.11), an
      enzyme that degrades substance P. Inhibition of neutral endopeptidase activity
      also potentiates substance P-induced 35SO4-labeled macromolecule secretion.
      Therefore we examined the in vitro effects of substance P on 35SO4-macromolecule
      secretion from the tracheae of influenza-infected ferrets. Despite a virus
      induced loss of neutral endopeptidase activity (demonstrated in muscle bath
      experiments), there was no difference between control and infected tracheae in
      either baseline secretion [697 +/- 125 vs. 579 +/- 67 (SE) cpm/15 min; n = 15
      tissues) or in the response to 10(-6) M substance P (increased by 218 +/- 63 and
      195 +/- 51, respectively) or 10(-5) M substance P (increased by 416 +/- 95 and
      354 +/- 54, respectively). Although phosphoramidon (10(-6) M) potentiated the
      secretory response to substance P, there was again no difference between control
      and infected tracheae. These data show that although viral infection decreases
      airway neutral endopeptidase activity, virus-induced hypersecretion is not due to
      a resulting increase in the secretory response to substance P.

PMID- 1373131
TI  - The anticodon and discriminator base are major determinants of cysteine tRNA
      identity in vivo.
AB  - Mutants of the Escherichia coli initiator tRNA (tRNA(fMet)) have been used to
      examine the role of the anticodon and discriminator base in in vivo
      aminoacylation of tRNAs by cysteinyl-tRNA synthetase. Substitution of the
      methionine anticodon CAU with the cysteine anticodon GCA was found to allow
      initiation of protein synthesis by the mutant tRNA from a complementary
      initiation codon in a reporter protein. Sequencing of the protein revealed that
      cysteine comprised about half of the amino acid at the N terminus. An additional
      mutation, converting the discriminator base of tRNA(GCAfMet) from A73 to the base
      present in tRNA(Cys) (U73), resulted in a 6-fold increase in the amount of
      protein produced and insertion of greater than or equal to 90% cysteine in
      response to the complementary initiation codon. Substitution of C73 or G73 at the
      discriminator position led to insertion of little or no cysteine, indicating the
      importance of U73 for recognition of the tRNA by cysteinyl-tRNA synthetase.
      Single base changes in the anticodon of tRNA(GCAfMet) containing U73 from GCA to
      UCA, GUA, GCC, and GCG (changes underlined) eliminated or dramatically reduced
      cysteine insertion by the mutant initiator tRNA indicating that all three
      cysteine anticodon bases are essential for specific aminoacylation of the tRNA
      with cysteine in vivo.

PMID- 1373132
TI  - Molecular cloning and expression of human alveolar macrophage cathepsin S, an
      elastinolytic cysteine protease.
AB  - Human alveolar macrophages (HAM) express an elastase activity of acidic pH
      optimum inhibitable by cysteine protease inhibitors. Recent studies indicate that
      the only known eukaryotic elastinolytic cysteine protease, cathepsin L, cannot
      completely account for this activity. In order to search for additional cysteine
      proteases with elastinolytic activity, low degeneracy oligonucleotide primers
      based on regions of strong homology among the known cysteine proteases were used
      to screen reverse-transcribed HAM RNA for cysteine proteases by the polymerase
      chain reaction. Among the cDNA sequences generated was a 493-base pair product
      highly homologous to bovine cathepsin S. Screening of a HAM cDNA eukaryotic
      expression library with this cDNA yielded a 1.7-kilobase full-length cDNA highly
      homologous to bovine cathepsin S (approximately 85% identical). This cDNA
      predicts a 331-amino acid preprocathepsin. Expression of this cDNA in COS cells
      revealed the active enzyme to be a single chain 28-kDa protease, as judged by
      active site labeling with a novel iodinated analogue of N-(L-3-trans
      carboxyoxirane-2-carbonyl)-L-leucylamido-(4-gua nido)butane (E-64). The
      recombinant enzyme was found to be elastinolytic toward 3H-labeled elastin
      (bovine ligamentum nuchae) at pH 5.5 but with 25% of this activity retained at pH
      7.0. Labeling of HAM with the active site probe revealed these cells express a 28
      kDa cysteine protease, and Northern blot analysis revealed the presence of a
      approximately 1.7-kilobase cathepsin S mRNA. These data establish that human
      macrophages express at least two cysteine proteases with elastinolytic activity.
      The relatively broad pH range of human cathepsin S activity suggests this enzyme
      may contribute to the contact-dependent elastase activity of live human alveolar
      macrophages.

PMID- 1373133
TI  - High-affinity IgE receptor-mediated stimulation of rat basophilic leukemia (RBL
      2H3) cells induces early and late protein-tyrosine phosphorylations.
AB  - We reported previously that stimulation of RBL-2H3 cells through the high
      affinity IgE receptor resulted in tyrosine phosphorylation of a 72-kDa protein
      (pp72) that was coupled to signal transduction. In the present study, although
      pp72 tyrosine phosphorylation was induced only by antigen triggering, stimulation
      of RBL-2H3 cells by either antigen or the calcium-ionophore A23187 led to
      increased tyrosine phosphorylation of a 110-kDa protein (pp110). This tyrosine
      phosphorylated protein was also observed when RBL-2H3 cells were transfected with
      the G protein-coupled m3 muscarinic receptor and then stimulated to secrete with
      carbachol. In contrast to tyrosine phosphorylation of pp72, antigen-induced pp110
      tyrosine phosphorylation required extracellular calcium, was absent in cells
      depleted of protein kinase C, and was detected between 1 and 5 min after
      stimulation. The protein-tyrosine kinase inhibitor genistein blocked both
      histamine release and tyrosine phosphorylation induced by A23187. Altogether, the
      data suggest a role for pp110 in secretion. However, protein kinase C activation
      induced pp110 tyrosine phosphorylation but not histamine release demonstrating
      that pp110 tyrosine phosphorylation alone is not sufficient for degranulation. We
      conclude that tyrosine phosphorylation of pp72 is associated with the early steps
      of IgE receptor-generated signaling, whereas pp110 tyrosine phosphorylation
      occurs secondary to calcium influx and protein kinase C activation.

PMID- 1373134
TI  - A structural homologue of the N-formyl peptide receptor. Characterization and
      chromosome mapping of a peptide chemoattractant receptor family.
AB  - Phagocytic cells of many higher species express calcium mobilizing G protein
      coupled receptors for bacterial N-formyl peptides which mediate chemotaxis,
      degranulation, and the respiratory burst. cDNA encoding an N-formyl peptide
      receptor (FPR) has been reported. We now report the isolation of a closely
      related cDNA, 2.6 kilobase pairs in length, which we have designated as the FPRL1
      receptor cDNA (FPRL1 = formyl peptide receptor like-1). FPR and the FPRL1
      receptor derive from small, single-copy genes, both of which are located on human
      chromosome 19. The gene loci are designated FPR1 and FPRL1, respectively. Both
      FPR and FPRL1 cDNA cross-hybridize under high stringency conditions with a third
      gene, designated as FPRL2, which does not appear to be expressed in neutrophils.
      In contrast, transcripts for both the FPRL1 receptor and FPR are detected only in
      differentiated myeloid cells; the distribution of N-formyl peptide binding sites
      is also restricted to mature myeloid cells. FPRL1 cDNA encodes a 351-amino acid
      polypeptide whose sequence is 69% identical to that of FPR. G protein-coupled
      receptors that exhibit this degree of structural similarity typically possess a
      conserved ligand specificity. However, the FPRL1 receptor does not bind prototype
      N-formyl peptide ligands when expressed in heterologous cell types. These results
      suggest that FPR1 may be the only gene that is expressed by neutrophils that
      encodes a receptor capable of binding prototype N-formyl peptides. Moreover,
      discovery of the FPRL1 receptor indicates the existence of another as yet
      unidentified peptide that may recruit neutrophils to sites of inflammation.

PMID- 1373135
TI  - Identification of the double-stranded RNA-binding domain of the human interferon
      inducible protein kinase.
AB  - The interferon-inducible double-stranded (ds) RNA-activated protein kinase (p68
      kinase) is a physiologically important enzyme that regulates the rate of cellular
      and viral protein synthesis by phosphorylating and thereby inactivating the
      peptide chain initiation factor 2. We have generated a cDNA clone of the human
      p68 kinase by polymerase chain reaction cloning using the recently published
      sequence of this enzyme. Active enzyme was synthesized by in vitro transcription
      translation of the cDNA clone. This system was used for mapping the dsRNA-binding
      domain of the enzyme. Progressive deletions from the carboxyl terminus were
      introduced by digesting the cDNA with suitable restriction enzymes. Expression of
      proteins harboring deletions from the amino terminus was achieved by cloning DNA
      fragments into appropriately constructed expression vectors. Affinity of the
      truncated proteins for dsRNA was examined by testing their capacity to bind to
      dsRNA-agarose beads. Our results demonstrated that the dsRNA-binding domain lies
      at the amino terminus of the protein. A truncated protein containing the first
      170 amino acid residues from the amino terminus could bind to dsRNA. However,
      deletion of 34 residues from the amino terminus or 41 residues from the carboxyl
      terminus of this truncated protein eliminated its dsRNA-binding activity.
      Comparison of the primary structure and the secondary structure of this region of
      p68 kinase and the corresponding region of 2'-5'-oligoadenylate synthetase
      revealed no apparent similarity.

PMID- 1373136
TI  - Positive autoregulation of the Vibrio fischeri luxR gene. LuxR and autoinducer
      activate cAMP-catabolite gene activator protein complex-independent and 
      dependent luxR transcription.
AB  - The LuxR protein is a transcriptional activator involved in regulation of the
      genes required for bioluminescence (lux) in the marine bacterium Vibrio fischeri.
      Transcription of the two divergently oriented lux operons (luxR and luxICDABEG)
      is activated by LuxR in the presence of a diffusible inducer (autoinducer).
      Transcription of the luxR gene is subject to both positive and negative
      autoregulation as well as activation by the cAMP-catabolite gene activator
      protein complex (cAMP-CAP). Transcription of luxR was studied using both
      luminescence in vivo as a reporter and primer extension analysis of mRNA
      synthesized in vivo. Mutation of the lux CAP-binding site resulted in a reduction
      in luminescence from the reporter and the complete loss of luxR positive
      autoregulation. Positive autoregulation was restored if luxR was provided in
      trans, demonstrating that LuxR and autoinducer activate luxR transcription in the
      absence of cAMP-CAP. By means of primer extension analysis, three sites of
      initiation of luxR transcription were demonstrated; initiation at two of these
      sites required cAMP-CAP. The quantity of all three transcripts was increased in
      the presence of LuxR and autoinducer when a plasmid with a wild-type CAP-binding
      site was used. Initiation at the cAMP-CAP-dependent sites was not observed from a
      plasmid with a mutated CAP-binding site in the presence or absence of autoinducer
      even with luxR supplied in trans. Instead, with luxR supplied in trans,
      initiation at the cAMP-CAP-independent initiation site was specifically
      stimulated by LuxR and autoinducer. Thus, in the course of positive
      autoregulation, the LuxR protein activates transcription from two luxR promoters
      by a cAMP-CAP-dependent mechanism and a third promoter by a cAMP-CAP-independent
      mechanism.

PMID- 1373138
TI  - The interferon-inducible 15-kDa ubiquitin homolog conjugates to intracellular
      proteins.
AB  - We have previously identified a 15-kDa interferon-induced protein that is
      recognized by affinity-purified rabbit polyclonal antibodies against ubiquitin
      (Haas, A. L., Ahrens, P., Bright, P. M., and Ankel, H. (1987) J. Biol. Chem. 262,
      11315-11323). This ubiquitin cross-reactive protein (UCRP) possesses significant
      homology to a tandem diubiquitin sequence. Since the biological effects of
      ubiquitin arise from its covalent ligation to intracellular target proteins, we
      hypothesized that the multiple cellular responses to inteferon are mediated in
      part by an analogous conjugation pathway for UCRP. Rabbit polyclonal antibodies
      specific for UCRP were prepared against homogeneous recombinant protein. Affinity
      purified anti-UCRP antibodies detected the induction of UCRP in interferon-beta
      treated A549 cells and recognized a group of high molecular weight UCRP
      conjugates on immunoblots of sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis-resolved cell extracts. Both free and conjugated UCRP are
      constitutively present at low levels in untreated cells, suggesting a role for
      UCRP ligation in normal cellular regulation, and significantly accumulate
      following interferon treatment. The temporal induction of free UCRP following
      interferon treatment preceded a delayed increase in UCRP conjugates. Treatment of
      A549 cells with type I interferons (alpha and beta) strongly induced the
      expression of free and conjugated UCRP, whereas the response to type II
      interferon (gamma) was significantly less. A survey of selected cultured cell
      lines showed differential induction of free versus conjugated UCRP pools in
      response to interferon. Interferon-beta treatment of A549, MG63, and U937 cells
      induced high levels of both free and conjugated UCRP, whereas only free UCRP
      levels increased in Daudi, Namalwa, and K562 cells. These results confirm that
      UCRP represents a functional ubiquitin homolog participating in a parallel
      pathway of post-translational ligation and provides a novel mechanism for the
      response of susceptible cells to the effects of interferon exposure.

PMID- 1373137
TI  - Mechanistic studies of transcription arrest at the adenovirus major late
      attenuation site. Comparison of purified RNA polymerase II and washed elongation
      complexes.
AB  - Transcription elongation in a nuclear extract in vitro is efficiently blocked by
      Sarkosyl at a specific site downstream of the adenovirus major late (ML) promoter
      at which regulated transcription arrest has also been observed in vivo. In the
      experiments reported here, we examined the response of the polymerase to the ML
      attenuation site in two assay systems: 1) purified RNA polymerase II (pol II)
      transcribing tailed templates and 2) elongation complexes formed on immobilized
      templates and then depleted of elongation factors by extensive washing. Efficient
      site-specific arrest occurred in both systems, demonstrating that recognition of
      the site is an intrinsic property of the polymerase. However, the elongation
      properties of washed elongation complexes and purified pol II were not
      equivalent. In particular, the efficiency of arrest of washed elongation
      complexes was influenced both by the promoter from which transcription was
      initiated and by DNA sequences upstream from the attenuation site that did not
      contribute to the arrest of purified pol II. The polymerase and washed elongation
      complexes both remained in stable ternary complexes at the ML site with a
      lifetime of hours; addition of the elongation factor SII to these complexes
      promoted resumption of elongation. The efficiency of arrest in both systems was
      dependent on the solution concentration of the nucleotide incorporated at +187
      (just beyond the attenuation site), indicating that pausing is an important part
      of the arrest mechanism. Based on this and other findings, we argue that the
      polymerase assumes an altered, elongation-incompetent conformation when arrest
      occurs.

PMID- 1373139
TI  - Aberrant splicing caused by the insertion of the B2 sequence into an intron of
      the complement C4 gene is the basis for low C4 production in H-2k mice.
AB  - The serum level of the fourth component of complement (C4) in mice bearing the H
      2k haplotype is only 1/10 to 1/20 of that of non-H-2k mice. We have analyzed C4
      cDNA clones from B10.BR(H-2k) mouse liver and found aberrant C4 cDNA which
      contained a 200-base pair (bp) insertion between the exon 13 and exon 14 encoded
      sequences in addition to the normal C4 cDNA. The 5' 148 bp and the 3' 52 bp of
      this insert were derived from the B2 sequence, the short interspersed repeats of
      mouse genome, and the central part of intron 13, respectively. Sequence analysis
      of intron 13 of the C4k gene showed the presence of a complete copy of a B2
      consensus sequence. The structure of aberrant C4 mRNA indicated that the possible
      3' splice site in the B2 sequence and the cryptic 5' splice site in intron 13
      were used. Both the insertion of the B2 sequence into intron 13 and the presence
      of aberrant mRNA in the liver were specific to H-2k-bearing mice, suggesting that
      the aberrant splicing due to the B2 insertion is the basis for low C4 expression
      in H-2k mice.

PMID- 1373140
TI  - Molecular cloning of murine 72-kDa type IV collagenase and its expression during
      mouse development.
AB  - We report the isolation of a cDNA clone providing the first and complete sequence
      of mouse 72-kDa type IV collagenase. The clone contains 2800 nucleotides with a
      1986-nucleotide open reading frame coding for 662 amino acids. The amino acid
      sequence includes a 29-residue signal peptide, an 80-residue propeptide, and a
      553-residue enzyme proper. The sequence identity between the mouse and human
      enzymes is 96% with all cysteine residues conserved. The carboxyl-terminal domain
      of the mouse enzyme contains two more residues than the human enzyme. Northern
      hybridization analysis revealed considerable expression of the enzyme gene in
      newborn mouse lung, heart, kidney, and psoas muscle tissues, whereas only weak or
      no signals were observed in liver, spleen, and brain. Expression of the gene was
      substantially reduced in the same tissues of 3-month-old mice. In situ
      hybridization analysis of 72-kDa type IV collagenase expression in 10-15-day-old
      mouse embryos showed that the gene was intensely expressed in mesenchymal cells.
      Brain and surface ectoderm were completely negative. The epithelial tissue
      component of developing organs was negative with the exception of salivary gland.
      Although the expression varied somewhat between different mesenchymal tissues, no
      temporal or spatial changes could be associated with the advancement of
      epithelial branching morphogenesis. These findings together with our previous
      data on the expression of 72-kDa type IV collagenase in human tumors indicate
      that this enzyme has some very specific roles both in the physiological and
      pathological degradation of extracellular matrix. Furthermore, it has become
      clear that the closely related 92-kDa type IV collagenase differs completely with
      respect to expression pattern as well as gene regulation. The mouse cDNA clones
      reported in this study may provide important tools unraveling the actual roles of
      these enzymes in vivo.

PMID- 1373141
TI  - The protein tyrosine kinase p56lck inhibits CD4 endocytosis by preventing entry
      of CD4 into coated pits.
AB  - The lymphocyte glycoprotein CD4 is constitutively internalized and recycled in
      nonlymphoid cells, but is excluded from the endocytic pathway in lymphocytic
      cells (Pelchen-Matthews, A., J. E. Armes, G. Griffiths, and M. Marsh. 1991. J.
      Exp. Med. 173: 575-587). Inhibition of CD4 endocytosis is dependent on CD4
      expressing an intact cytoplasmic domain and is only observed in cells where CD4
      can interact with the protein tyrosine kinase p56lck, a member of the src gene
      family. We have expressed p56lck, p60c-src, or chimeras of the two proteins in
      CD4-transfected NIH-3T3 or HeLa cells. Immunoprecipitation of CD4 and in vitro
      kinase assays showed that p56lck and the lck/src chimera, which contains the NH2
      terminus of p56lck, can associate with CD4. In contrast, p60c-src and the src/lck
      chimera, which has the NH2 terminus of p60c-src, do not associate with CD4.
      Endocytosis assays using radioiodinated anti-CD4 monoclonal antibodies
      demonstrated that coexpression of CD4 with p56lck, but not with p60c-src,
      inhibited CD4 endocytosis, and that the extent of the inhibition depended
      directly on the relative levels of CD4 and p56lck expressed. The uptake of mutant
      CD4 molecules which cannot interact with p56lck was not affected. Measurement of
      the fluid-phase endocytosis of HRP or the internalization of transferrin
      indicated that the effect of p56lck was specific for CD4, and did not extend to
      other receptor-mediated or fluid-phase endocytic processes. Immunogold labeling
      of CD4 at the cell surface and observation by electron microscopy demonstrated
      directly that p56lck inhibits CD4 endocytosis by preventing its entry into coated
      pits.

PMID- 1373142
TI  - Distribution of the Na(+)-Ca2+ exchange protein in mammalian cardiac myocytes: an
      immunofluorescence and immunocolloidal gold-labeling study.
AB  - The present study reports on the location of the Na(+)-Ca2+ exchanger in cardiac
      sarcolemma with immunofluorescence and immunoelectron microscopy. Both polyclonal
      and monoclonal antibodies to the Na(+)-Ca2+ exchanger were used. The mAb was
      produced from a hybridoma cell line generated by the fusion of mouse myeloma NS-1
      cells with spleen cells from a mouse repeatedly immunized with isolated
      reconstituted canine cardiac Na(+)-Ca2+ exchanger (Philipson, K. D. S. Longoni,
      and R. Ward. 1988. Biochim. Biophys. Acta. 945:298-306). The polyclonal antibody
      has been described previously and reacts with three proteins (70, 120, 160 kD) in
      cardiac sarcolemma associated with the Na(+)-Ca2+ exchanger (Nicoll, D. A., S.
      Longoni, and K. D. Philipson. 1990. Science (Wash. DC). 250:562-565). Both the
      monoclonal and the polyclonal antibodies appear to react with extracellular
      facing epitopes in the cardiac sarcolemma. Immunofluorescence studies showed
      labeling of the transverse tubular membrane and patchy labeling of the peripheral
      sarcolemma. The immunofluorescent labeling clearly delineates the highly
      interconnected T-tubular system of guinea pig myocytes. This localization of the
      exchanger to the sarcolemma, with an apparent high density in the transverse
      tubules, was also seen with immunoelectron microscopy. It is of great interest
      that the Na(+)-Ca2+ exchanger, as the main efflux route for Ca2+ in heart cells,
      would be abundantly located in sarcolemma closest to the release of Ca2+.

PMID- 1373143
TI  - Expression of a protein tyrosine phosphatase in normal and v-src-transformed
      mouse 3T3 fibroblasts.
AB  - A rat cDNA encoding a 51-kD protein tyrosine phosphatase (PTP1) was cloned into a
      mammalian expression vector and transfected into normal and v-src-transformed
      mouse NIH 3T3 fibroblasts. In the stable subclones isolated, PTP1 expression at
      the mRNA level was elevated twofold to 25-fold. The highest constitutive level of
      phosphotyrosine-specific dephosphorylating activity observed without cytotoxic
      effects or significant clonal instability was approximately 10-fold over the
      endogenous activity. The expressed PTP1 was found to be associated with the
      particulate fraction of the fibroblasts. Subcellular fractionation and
      immunofluorescent microscopic examination of PTP1-overexpressing cells has shown
      the phosphatase to be localized to the reticular network of the ER. PTP1 was
      readily solubilized by detergents, but not by high salt. Limited proteolysis of
      membrane-associated PTP1 resulted in the release of lower molecular mass (48 and
      37 kD) forms of the enzyme to the cytosol. Thermal phase partitioning of isolated
      membranes with Triton X-114 indicated that the full-length PTP1 was strongly
      integrated into the membrane in contrast to the proteolytically derived fragments
      of PTP1. Overexpression of PTP1 caused little apparent change in the rate of cell
      proliferation, but did induce changes in fibroblast morphology. A substantial
      increase in the proportion of bi- and multinucleate cells in PTP1-expressing cell
      populations was observed, and, in the case of the v-src-transformed cells, cell
      flattening and loss of refractibility occurred. Although no apparent difference
      in the tyrosine phosphorylation of pp60v-src was noted in v-src-transformed
      control and PTP1-overexpressing fibroblasts, the phosphotyrosine content of a 70
      kD polypeptide was decreased in PTP1-overexpressing cells.

PMID- 1373144
TI  - Regulation of keratinocyte intercellular junction organization and epidermal
      morphogenesis by E-cadherin.
AB  - Elevation of the calcium concentration in human keratinocyte culture rapidly
      induces the redistribution of E-cadherin, P-cadherin, vinculin, beta 1 integrin,
      and desmoplakin to the cell-cell borders. Antibody to E-cadherin that blocks its
      functional activity delays the redistribution of each marker by several hours.
      Furthermore, antibody to E-cadherin interferes with normal, calcium-induced
      stratification of keratinocytes. Although several uneven vertical layers of cells
      can be detected in the presence of anti-E-cadherin antibody, the superficial
      cells appear defective in their adhesion. They do not flatten upon the basal
      layer nor do they enlarge, as do the controls; but rather they remain in groups
      of small cells connected by a line of single cells or by very long processes. In
      spite of the deformed appearance of the superficial cells in the presence of anti
      E-cadherin IgG, these cells express the differentiation marker filaggrin, do not
      express P-cadherin, and concentrate desmoplakin at their cell-cell borders,
      consistent with the pattern in normally stratified cultures and in epidermis.
      These studies suggest a central role for E-cadherin in the regulation of
      keratinocyte intercellular junction organization as well as in epidermal
      morphogenesis.

PMID- 1373145
TI  - Regulation of fibronectin receptor distribution.
AB  - To determine the role of each intracellular domain of the fibronectin receptor in
      receptor distribution, chimeric receptors were constructed containing the human
      interleukin-2 receptor (gp55 subunit) as the extracellular and transmembrane
      domains, in combination with either the alpha 5 or beta 1 intracellular domain of
      the fibronectin receptor as the cytoplasmic domain. These chimeric receptors were
      transiently expressed in normal fibroblasts, and their localization on the cell
      surface was determined by immunofluorescence using antibodies to the human
      interleukin-2 receptor. The alpha 5 chimera was expressed diffusely on the plasma
      membrane. The beta 1 chimera, however, colocalized with the endogenous
      fibronectin receptor at focal contacts of cells spread on fibronectin. On cells
      spread in the presence of serum, the beta 1 chimera colocalized both with the
      fibronectin receptor at sites of extracellular fibronectin fibrils and with the
      vitronectin receptor at focal contacts. The beta 1 intracellular domain alone,
      therefore, contains sufficient information to target the chimeric receptor to
      regions of the cell where ligand-occupied integrin receptors are concentrated.
      The finding that the beta 1 chimeric protein behaves like a ligand-occupied
      receptor, even though the beta 1 chimera cannot itself bind extracellular ligand,
      suggests an intracellular difference between occupied and unoccupied receptors,
      and predicts that the distribution of integrin receptors can be regulated by
      ligand occupancy. We tested this prediction by providing a soluble cell-binding
      fragment of fibronectin to cells spread on laminin. Under conditions preventing
      further ligand adsorption to the substrate, this treatment nevertheless resulted
      in the relocation of diffuse fibronectin receptors to focal contacts. Similarly,
      a redistribution of diffuse vitronectin receptors to focal contacts occurred on
      cells spread on laminin after the addition of the small soluble peptide GRGDS. We
      conclude that the propensity for receptor redistribution to focal contacts driven
      by the beta 1 cytoplasmic domain alone is suppressed in heterodimeric unoccupied
      fibronectin receptors, and that ligand occupancy can release this constraint.
      This redistribution of integrin receptors after the binding of a soluble
      substrate molecule may provide a direct means of assembling adhesion sites.

PMID- 1373146
TI  - Transformation of renal tubule epithelial cells by simian virus-40 is associated
      with emergence of Ca(2+)-insensitive K+ channels and altered mitogenic
      sensitivity to K+ channel blockers.
AB  - We compared the pattern of K+ channels and the mitogenic sensitivity to K+
      channel blocking agents in primary cultures of rabbit proximal tubule cells
      (PC.RC) (Ronco et al., 1990) and two derived SV-40-transformed cell lines
      exhibiting specific functions of proximal (RC.SV1) and more distal (RC.SV2)
      tubule cells (Vandewalle et al., 1989). First, K+ channel equipment surveyed by
      the patch-clamp technique was modified after SV-40 transformation in both cell
      lines; although a high conductance Ca(2+)-activated K+ channel [K+200 (Ca2+)]
      remained the most frequently recorded K+ channel, the transformed state was
      characterized by emergence of three Ca(2+)-insensitive K+ channels (150, 50, and
      30 pS), virtually absent from primary culture, contrasting with reduced frequency
      of two Ca(2+)-sensitive K+ channels (80 and 40 pS). Second, quinine (Q),
      tetraethylammonium ion (TEA) and charybdotoxin (CTX), at concentrations not
      affecting cell viability, all decreased 3H-TdR incorporation and cell growth in
      PC.RC cultures, but only TEA had similar effects in transformed cells. The latter
      were further characterized by paradoxical effects of Q that induced a marked
      increase in thymidine incorporation. Q also exerted contrasting effects on
      channel activity: it inhibited the [K+200 (Ca2+)] when the channel was highly
      active, with a Ki (0.2 mM) similar to that measured for 3H-TdR incorporation in
      PC.RC cells (0.3 mM), but increased the mean current through poorly active
      channels. TEA blocked all K+ channels with conductance greater than or equal to
      50 pS, including the [K+200 (Ca2+)], in a range of concentrations that
      substantially affected cell proliferation. The unique effect of TEA on SV-40
      transformed cells might be related to broad inhibition of K+ channels.

PMID- 1373147
TI  - Multipotent marrow stromal cell line is able to induce hematopoiesis in vivo.
AB  - Several murine marrow stromal cells were established from murine bone marrow
      cultures. Stromal cell lines transfected with a tumor-inducing polyoma virus
      middle T antigen (MTAg) were inoculated into nude mice subcutaneously. KUSA-MTAg
      cells, one of these cell lines, led to the rapid local development of bone marrow
      consisting of trilineage hematopoietic cells and bone; other cell lines produced
      spindle cell sarcoma or hemangiosarcoma. These results suggested that a single
      stromal cell line, KUSA-MTAg cells, may induce hematopoietic stem cells or early
      progenitors of three lineages of hematopoietic cells in vivo. Interestingly,
      untransfected KUSA cells expressed three new mesenchymal phenotypes, osteocytes,
      adipocytes, and myotubes, after treatment with 5-azacytidine.

PMID- 1373148
TI  - Repression of SV40 T oncoprotein expression by DMSO.
AB  - SV40 large T oncoprotein-transformed murine mesenchymal 3T3 T stem cells (CSV3
      cells) can be induced to growth arrest and then differentiate into adipocytes.
      When differentiation occurs, SV40 T oncoprotein expression is repressed (Estervig
      et al., J Virol 63:2718, 1989). To determine if repression of T oncoprotein
      expression can also be induced pharmacologically, the effect of a variety of
      agents that have been reported to effect differentiation in various cell types
      but not in 3T3 T or CSV3 cells was tested. This rationale suggests that if any of
      these agents repress T oncoprotein expression in CSV3 cells, then the results
      would establish that repression of T oncoprotein expression can be mediated by
      mechanisms independent of overt differentiation. The results show that
      dimethylsulfoxide (DMSO) is the only agent tested that represses T oncoprotein
      expression in CSV3 cells. Repression occurs in a dosage-dependent manner within
      24-96 hours after exposure to DMSO. The effect of DMSO on T oncoprotein
      expression is mediated by posttranslational mechanisms that decrease the
      stability of the T oncoprotein. DMSO-induced repression of T oncoprotein
      expression is also associated with reversion of the transformed phenotype in CSV3
      cells as demonstrated by the loss of responsiveness to a specific transformation
      associated mitogen. These data support the conclusion that the pharmacological
      repression of T oncoprotein expression represents a form of cancer suppressor
      activity that can be mediated by a distinct molecular mechanism.

PMID- 1373149
TI  - Differential isotype expression and binding properties of T cell-reactive
      antibodies in human immunodeficiency virus (HIV) infection.
AB  - Isotype and binding characteristics of T cell-reactive antilymphocyte antibodies
      (ALA) were investigated in 287 human immunodeficiency virus (HIV)+ sera from
      patients with CDC II to IVC clinical disease. Using purified soluble T
      lymphoblast (CEM cell line) membranes and an ELISA method, 29 HIV+ sera showed
      significant reactions with this substrate and a selective expression of IgG-ALA
      was detected in 7 HIV+ sera. Subsequent microcytotoxicity assays, utilizing
      peripheral T lymphocytes and CEM cells as targets, demonstrated no significant
      cytotoxic capability in such sera, whereas 12 of 17 HIV+ serum samples with IgM
      ALA ELISA reactivities showed a significant degree of killing in the Terasaki
      test. Further experiments of saturation of CD4 molecules on CEM extract by OKT4
      monoclonal antibody (MoAb) induced a high inhibition of IgG-ALA binding to the T
      cell membranes in only two IgG-ALA+ sera (No. 93, CDC III; No. 179, CDC II
      stage). Conversely, treatment of CEM membrane lysate with Leu3a MoAb, specific
      for the gp120 reactive domain of the HIV receptor, failed to prevent membrane
      binding in all seven of the IgG-ALA+ sera. Following the adsorption of serum 93
      on a T-cell membrane antigen affinity column, SDS-PAGE analysis demonstrated that
      the predominant ALA material reacting with T-cell membranes was IgG with no
      detectable traces of IgM. These data provide evidence that ALA in HIV+ patients
      may be simultaneously or selectively expressed as IgG and/or IgM with different
      properties.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373150
TI  - Frequent anti-V-region immune response to mouse B72.3 monoclonal antibody.
AB  - The immune response of 56 colorectal cancer patients to a single infusion of 1 mg
      of radiolabeled (111In) mouse B72.3-GYK-DTPA immunoconjugate was examined using a
      double-antigen radiometric assay system. The incidence of antibody response was
      48% to polyclonal mouse IgG, 71% to mouse B72.3, and 62% to chimeric B72.3.
      Twelve patients (23%) had an antibody response to B72.3 V region in the absence
      of binding to polyclonal mouse IgG. An antiidiotype response was demonstrated in
      sera from 36% of 25 patients examined and correlated well with chimeric B72.3-GYK
      DTPA immunoconjugate binding (r = 0.72, moderately well with mouse B72.3 binding
      (r = 0.56), and not at all with polyclonal mouse IgG binding (r = 0.28). The peak
      antibody response occurred most frequently 2 weeks postinfusion, although a
      "delayed" peak response to chimeric B72.2 occurred in 29% of patients. This study
      suggests that mouse B72.3 causes an immune response in the majority of patients
      and that antibody response to the V region is common. Understanding the
      physiological significance of these antibody responses will require correlation
      with the kinetics and tumor localization of repeat infusions of such
      immunoconjugates.

PMID- 1373151
TI  - Phenotypic expression of integrin membrane receptors on spontaneously
      proliferating CD8 cells in human T-lymphotropic virus type II (HTLV-II)-infected
      individuals.
AB  - Spontaneous lymphocyte proliferation in the absence of exogenous stimulators was
      examined in asymptomatic HTLV-II-seropositive (n = 12) and seronegative
      individuals (n = 16). Mean spontaneous lymphocytic proliferation significantly
      increased on day 8 postculture in HTLV-II-infected individuals (5762 +/- 899 cpm)
      compared with normal controls (2034 +/- 925 cpm, P less than 0.01). The
      proliferating cells in infected individuals were predominantly T cells; neither B
      cells nor monocytes demonstrated any proliferation. Phenotypic analysis of
      cultured cells from individuals with HTLV-II infection demonstrated differential
      expression of integrin molecules as defined by anti-CD29 and anti-S6F1 (42.8 +/-
      4.2 and 39.6 +/- 5.9%, respectively) on CD8 cells, as compared with day 0
      peripheral blood mononuclear cells (PBMC) from infected individuals (19.7 +/- 3.5
      and 19.9 +/- 1.9%, respectively) or normal controls (12.9 +/- 3.1 and 11.5 +/-
      2.5%, respectively; P less than 0.001 for both comparisons). These CD8+ cells did
      not express CD16 or CD11b. The culture supernatants derived from the
      spontaneously proliferating cells had significantly increased levels of sCD8 and
      sCD25 (765 +/- 180 and 1805 +/- 320 U/ml, respectively) compared with those from
      normal controls (222 +/- 120 and 305 +/- 90 U/ml, respectively; P less than
      0.01). Furthermore, culture supernatants derived from spontaneously proliferating
      PBMC from HTLV-II-infected individuals had no detectable levels of HTLV antigen
      and did not stimulate proliferation of PBMC from normal donors. These results
      suggest that the spontaneous proliferation in HTLV-II asymptomatic carriers is
      due to expansion of CD8 cells expressing integrin receptors which may serve as
      costimulatory molecules for their activation.

PMID- 1373152
TI  - Selective deficiency of CD4+/CD45RA+ lymphocytes in patients with ataxia
      telangiectasia.
AB  - Several immunological abnormalities have been observed in ataxia-telangiectasia
      (AT), the most consistent being defects of immunoglobulin isotypes, decreased T
      cell numbers, and reduced proliferative responses to mitogens. We examined the
      distribution of T lymphocytes expressing distinctive surface Ag characteristic of
      "naive" (CD45RA+) and "memory" (CD29+, CD45RO+) T cells, in both CD4+ and CD8+
      (bright and dim) lymphocytes from 13 AT patients, compared with healthy age
      matched controls. We found that, irrespective of age, patients with AT had a
      severe deficiency of CD4+/CD45RA+ lymphocytes. This decrease accounted for the
      reduction of total CD4+ cells, since the absolute numbers of memory CD4+ cells
      were not significantly different in AT and in controls. Functional tests revealed
      poor proliferative responses to phytohemagglutinin and normal responses to
      soluble Ag (tetanus toxoid) in AT patients. These data fit with the distribution
      of naive and memory cells, which are known to respond predominantly to mitogens
      or to recall Ag, respectively. CD45RA molecules were normally expressed on CD8+
      lymphocytes. This rules out a generalized defect of regulation or differential
      splicing as the cause of defective expression of CD45RA on CD4+ cells. The
      selective deficiency of CD4+CD45RA+ may provide a cellular basis for some
      functional T-cell abnormalities of AT patients. Furthermore, it might practically
      serve for an early, or even prenatal, diagnosis of this disease.

PMID- 1373153
TI  - Antigen-specific inhibition of the adoptive transfer of experimental autoimmune
      encephalomyelitis in Lewis rats.
AB  - The efficacy of antigen-specific immunoregulation as a treatment for the efferent
      limb of an autoimmune disease was tested in a rat model of adoptive experimental
      autoimmune encephalomyelitis (EAE). Lewis rats receiving 4-5 x 10(7) guinea pig
      (GP) myelin basic protein (MBP)-activated lymph node T cell blasts from GPMBP/CFA
      sensitized donors routinely show clinical signs of disease 5-6 days post
      transfer. Intravenous injection of GPMBP coupled to syngeneic splenocytes using
      the chemical cross-linker carbodiimide was effective in completely abrogating the
      expression of clinical EAE in rats that received MBP-specific T cells 2 days
      previously. Partial inhibition was also observed in rats injected as early as day
      0 (the same day as MBP-specific T cell transfer) and as late as 1 day prior to
      the onset of clinical signs (days 4-5 post transfer). Unresponsiveness was shown
      to be dose-dependent, dependent on the route of injection of the neuroantigen
      coupled splenocytes, and was antigen-specific. Splenocytes coupled with GP or rat
      MBP (which are identical within the major encephalitogenic GP68-86 Lewis rat
      determinant with the exception of the residue at position 80) were equally
      efficient at eliminating disease expression in recipients of GPMBP-specific T
      cells. In contrast, splenocytes coupled with bovine or rabbit MBP (which differ
      significantly from GPMBP within the 68-86 region) had no inhibitory effect. The
      antigen specificity of the tolerance induction was also illustrated by the fact
      that splenocytes coupled with GP68-86, but not those coupled with the truncated
      GP68-84 peptide, induced profound unresponsiveness. Interestingly, de novo
      antigen processing by the antigen-coupled cells did not appear to be necessary as
      the inclusion of antigen processing inhibitors had no effect on inhibition of
      disease. However, the use of the carbodiimide coupling reagent was critical for
      the induction of unresponsiveness as essentially equivalent amounts of 125I
      labelled MBP were bound in its presence or absence, but only splenocytes
      incubated in the presence of both MBP and carbodiimide inhibited clinical
      expression of disease. Antigen-specific tolerance is thus an effective means of
      inhibiting expression of clinical disease in the rat EAE model, and a powerful
      tool for determining the fine epitope specificity of encephalitogenic T cells.

PMID- 1373154
TI  - The synthetic 87-99 peptide of myelin basic protein is encephalitogenic in
      Buffalo rats.
AB  - A synthetic peptide corresponding to residues 87-99 (S87-99) of myelin basic
      protein (BP) induced the proliferation of an encephalitogenic, BP-specific T cell
      line selected in vitro from inbred Buffalo-strain rats (RT1b). Active
      immunization with guinea pig (GP)-BP or S87-99 in complete Freund's adjuvant
      (CFA) and intravenous pertussigen induced acute experimental autoimmune
      encephalomyelitis (EAE) 10-12 days after immunization. Fifty percent of recovered
      rats developed a single relapse 17-21 days after immunization. T lymphocytes
      selected in vitro with S87-99 transferred acute, non-relapsing EAE into naive
      recipients. Histological examination during acute EAE revealed foci of
      inflammatory cells associated with demyelination in the spinal cords and
      peripheral nerve roots. Thus, as in several other rodent strains, the 87-99
      region of BP is antigenic and encephalitogenic in the inbred Buffalo-strain rat.
      Additionally, the 87-99 sequence of GP-BP was predicted to be antigenic by two
      different methods. These results suggest that the 87-99 region of BP, which is
      highly conserved among mammalian species, may be widely encephalitogenic due to
      antigen-intrinsic properties.

PMID- 1373155
TI  - Selective localisation of neuro-specific T lymphocytes in the central nervous
      system.
AB  - Using experimental autoimmune encephalomyelitis (EAE) in the rat as a model of
      central nervous system (CNS) inflammation, activated and quiescent T lymphocytes
      with different antigen specificities were labelled with the fluorescent dye
      Hoechst 33342 and tested by fluorescence microscopy for their ability to
      accumulate in different regions of the spinal cord and in other organs at varying
      times post inoculation. With this highly sensitive assay it was found that
      activated myelin basic protein (MBP)-specific T cell lines accumulated in the
      spinal cord (a 1000-fold increase in the lumbar/sacral region by day 4) and
      caused clinical signs of EAE. In contrast, interleukin-2 (IL-2)-maintained
      (quiescent) MBP-specific T cell lines failed to accumulate in the CNS and cause
      disease. Activated ovalbumin (OA)-specific and purified protein derivative of
      tuberculin (PPD)-specific T cell lines were also found at significantly higher
      levels in the spinal cord than non-activated cells although they failed to
      accumulate to a substantial degree when injected alone. When injected with
      activated MBP-specific T cells the activated OA- and PPD-specific cell lines
      accumulated in the spinal cord following initial accumulation of the MBP-specific
      cells, demonstrating that during the inflammatory process there is considerable
      non-specific recruitment of cells into the inflammatory site. CNS accumulation of
      activated MBP-specific T cell lines occurred 1-2 days later in irradiated animals
      than in non-irradiated recipients. This was consistent with irradiated animals
      also exhibiting a later onset of disease and suggests that irradiation may
      directly affect the endothelium in a way that makes it less adhesive. In
      conclusion, this study demonstrates that activated lymphocytes of any specificity
      enter the spinal cord, and that the neuro-antigen specific cells accumulate there
      and lead to the recruitment of other cells. Non-activated cells, even those with
      neural antigen specificity fail to enter the cord. Understanding the nature of
      what an 'activated' lymphocyte is may allow us to design strategies to inhibit
      such immune-mediated inflammation.

PMID- 1373156
TI  - Assessment of value of pancreatic pseudocyst amylase concentration in the
      treatment of pancreatic pseudocysts by percutaneous evacuation.
AB  - The aim of our study was to determine the value of the percutaneous pancreatic
      pseudocyst evacuation. We assessed the relation between the amylase concentration
      of the pseudocyst contents and the final outcome of the disease treated by the
      percutaneous evacuation. Forty-three patients with a history of acute
      pancreatitis and pancreatic pseudocysts larger than 5 cm in diameter that
      persisted beyond 6 weeks were divided into four groups relative to the amylase
      concentration in the pseudocystic contents and the number of evacuations. The
      results show a good correlation between low amylase concentration in the liquid
      pseudocystic contents (less than or equal to 64 WU) and the healing rate after
      the percutaneous evacuation (p less than 0.001). The percutaneous evacuation of
      the pseudocysts failed in patients with increased amylase concentrations in the
      pseudocyst fluid regardless of the number of evacuations. We conclude that
      surgical treatment is indicated in patients who have amylase-rich pseudocyst
      contents.

PMID- 1373157
TI  - Octopamine immunoreactive cell populations in the locust thoracic-abdominal
      nervous system.
AB  - We describe octopamine-immunoreactive somata and their projections in the pro-
      meso-, meta- and pregenital abdominal-ganglia of locusts. Immunoreactive midline
      somata were identified as dorsal- and ventral- unpaired median (DUM- and VUM-,
      respectively) neurones due to their: characteristic large size and positions of
      somata, primary neurites in DUM-tracts giving rise to T-junctions, and
      bilaterally projecting axons. In the prothoracic ganglion there are most likely 8
      such cells; in the meso- and metathoracic, some 20 each; and in each individual
      pregenital abdominal ganglion, typically 3. All appear to project to peripheral
      nerves and their numbers correspond to the number of peripherally projecting DUM
      cells identified to date in each ganglion. We suggest that probably all
      peripherally projecting DUM-cells are octopaminergic in the examined ganglia.
      Presumptive DUM-interneurones are not octopamine-immunoreactive, but, confirming
      other studies, are shown to label with an antiserum to gamma-amino butyric acid
      (GABA). Other octopamine-immunoreactive neurones include a pair of midline,
      prothoracic, anterior medial cells, not necessarily DUM-cells, and a pair of
      ventral lateral somata in each thoracic- and the first abdominal ganglion. The
      latter project intersegmentally in ventral tracts. Intersegmentally projecting
      octopamine-immunoreactive fibers in dorsal tracts probably arise from a
      prothoracic DUM-cell, which leaves through suboesophageal nerves, or descending
      suboesophageal DUM-cells. Thus, the octopamine-immunoreactive system of thoracic
      and pregenital abdominal ganglia in locust comprises all peripherally projecting
      DUM-cells and a plurisegmental network.

PMID- 1373158
TI  - Central projections of axons from taste hairs on the labellum and tarsi of the
      blowfly, Phormia regina Meigen.
AB  - Taste hairs are located on the labellum and tarsi of blowflies. These multimodal
      hairs consist of four functionally distinct chemoreceptors and a mechanoreceptor.
      By staining selected multimodal hairs, we sought to identify the central
      projection patterns of multiple and single axons from those hairs. On each side
      of the labellum there are 11 "largest" hairs (LH). The neurons associated with
      the anteriormost (LH-1), posteriormost (LH-11), and one lateral (LH-6) hair on
      the labellum were stained selectively with cobaltous sulfide. The overall
      projection pattern in the central nervous system (CNS) for axons from LH-1 and LH
      11 is similar and differs markedly from axons from LH-6. At least three
      individual axon-projection patterns were determined for each labellar hair
      filled, indicating a partial functional organization for axons from multimodal
      hairs. One identified axon, the dorsalmost axon, has terminal arborizations that
      do not differ with the location of its associated hair. Another axon, thicker
      than the others, projects to a region that is distinct from the four thin axons.
      Within this region the arborizations of the thick axons occupy different areas
      depending on the location of their associated hair. Neurons from the largest
      hairs on the distalmost tarsomere (D5) of each leg were also stained and
      consisted of one thick and four thin axons. All axons except one thin axon from
      tarsal D5 hairs terminate in their respective leg neuromeres. The remaining thin
      axon projects to the suboesophageal ganglion ipsilateral to the hair filled and
      terminates in the same region as a branch of the labellar dorsalmost axon. These
      data suggest that axonal arbors from multimodal hairs have a limited functional
      and somatotopic organization in the blowfly CNS.

PMID- 1373159
TI  - Substance P innervation of the rat and cat thalamus. I. Distribution and relation
      to ascending spinal pathways.
AB  - An antiserum for substance P (SP) with minimal cross-reactivity for other
      tachykinins was employed to map the distribution of SP-positive nerve fibers and
      terminals in the thalamus of cats and rats with special emphasis on the
      innervation by these fibers of nuclei related to the somatosensory system. In
      both species SP innervation is predominantly along the midline, in medial and
      posterior thalamic regions, and sparser in sensory relays for specific
      modalities. Among the most densely innervated nuclei are the parafascicular,
      paraventricular, rhomboid, central medial and parts of mediodorsal, lateral
      posterior, and ventral lateral geniculate. SP innervation of somatosensory
      related nuclei is also evident in central lateral nucleus, posterior complex
      (PO), and in ventroposterolateral (VPL) nucleus of both cats and rats. In VPL of
      cats SP fibers and terminals are present along its ventral and lateral border, a
      paralaminar area in which spinothalamic fibers have been shown to terminate and
      where neurons responsive to noxious stimuli have been reported. Also in rats the
      SP innervation of VPL is similar to that of spinothalamic tract fibers. The SP
      innervation of somatosensory thalamic nuclei may be supplied, at least in part,
      by spinothalamic afferent as suggested by the depletion of SP after anterolateral
      chordotomy but not after ablation of the dorsal column nuclei. The presence of SP
      positive spinothalamic neurons in the spinal cord is reported in the following
      paper.

PMID- 1373160
TI  - Substance P innervation of the rat and cat thalamus. II. Cells of origin in the
      spinal cord.
AB  - Evidence in the preceding paper suggests that fibers and terminals immunopositive
      for substance P (SP) in somatosensory thalamic nuclei are part of the
      spinothalamic tract (STT). In this paper, more direct evidence on this point is
      provided by immunocytochemistry for SP on the cervical spinal cord, alone or
      combined with the retrograde transport of colloidal gold-labeled wheat germ
      agglutinin conjugated to enzymatically inactive horseradish peroxidase (WGAapoHRP
      Au). In cats and rats pretreated with colchicine and/or anterolateral chordotomy
      (to increase SP content in cell bodies), many small to large cell bodies are SP
      immunopositive especially in laminae I and V, but also in more ventral laminae of
      the upper cervical cord. SP neurons are also present in the dorsolateral
      funiculus (in the lateral spinal nucleus, LSN, in rats) but not in the lateral
      cervical nucleus or in the internal basilar nucleus. In both species there is a
      considerable degree of overlap in the distribution of SP-positive neurons and
      that of STT neurons. SP immunocytochemistry in rats after WGAapoHRP-Au injection
      in the somatosensory thalamus reveals SP-positive STT neurons in LSN, in lamina I
      and in lamina V, and, to a lesser extent, in more ventral laminae. These results
      demonstrate that SP is a marker and/or neuromediator for some STT neurons.
      Together with the evidence discussed in the preceding paper, the results also
      suggest that SP-positive neurons may be involved in the transmission of
      nociceptive input.

PMID- 1373161
TI  - House dust mite-specific T cells in the skin of subjects with atopic dermatitis:
      frequency and lymphokine profile in the allergen patch test.
AB  - The mechanism underlying positive patch tests with house dust mite-allergen,
      Dermatophagoides pteronyssinus (Der p), in patients with atopic dermatitis was
      investigated by isolating T cells from the test sites of two patients. Eighty
      five T cell clones (TCC) were established from the epidermis and dermis of
      lesional skin by the limiting-dilution method with Der p and interleukin (IL)-2.
      With restimulation assays, 29 of 60 TCCs tested demonstrated specific
      proliferation; 85% were of the CD3+, CD2+, and CD4+ phenotype. Der p-specific T
      cells constituted 0.4% to 2.7% of lesional T cells, and they were more frequent
      in the skin than in the blood of the patients by one order of magnitude. The
      mitogen-stimulated lymphokine profile of 55 TCCs was assessed; 42% (11/26) of the
      allergen-specific TCCs secreted IL-4 but almost no interferon-gamma, as described
      for the Th2 subset of the mouse. Also, six selected TCCs supported IgE secretion
      by autologous lymphocytes. Only three of 26 allergen-specific, skin-derived TCCs
      demonstrated a Th1-like lymphokine profile. These results support the specific
      nature of Der p-induced patch test lesions in patients with atopic dermatitis,
      and the results demonstrate also that a considerable proportion of lesional T
      cells are allergen-specific, IL-4-producing T cells that are capable of enhancing
      IgE production.

PMID- 1373162
TI  - Monoclonal antibodies against Olea europaea major allergen: allergenic activity
      of affinity-purified allergen and depleted extract and development of a
      radioimmunoassay for the quantitation of the allergen.
AB  - Several monoclonal antibodies (MAbs) were raised against Olea europaea pollen
      extract components. Two of these antibodies, named OL 2 and OL 7, recognize two
      nonoverlapping, nonrepeating epitopes on the olive-allergen Ole e I, as
      demonstrated by different techniques. The allergen was purified in a single step
      by MAb-based affinity chromatography, and the allergen revealed a band at
      molecular weight 20 kd as well as a minor band at 18 kd on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The contribution of allergen Ole e I to the
      allergenic activity of O. europaea pollen extracts was determined from the effect
      of allergen depletion by affinity chromatography on skin reactivity and a
      histamine-release test. The removal of allergen caused a large reduction in the
      activity of the preparation in 25 monospecific olive-allergic patients. In
      agreement, the affinity-purified allergen demonstrated a similar response when it
      was compared with the whole extract in these assays. The results indicated that
      Ole e I is by far the most important olive-pollen allergen. A two-site solid
      phase radioimmunoassay was developed for the quantitation of the allergen Ole e I
      in mass units. The assay was based on the MAbs, OL 2 and OL 7, and had a
      detection limit in the nanogram range. A good correlation was found between
      allergenic activity, as determined by RAST inhibition, and allergen content in 18
      olive-pollen extracts. This result indicates that the assay can be a good
      alternative to RAST inhibition for the standardization of O. europaea extracts.

PMID- 1373163
TI  - A new quantitative polymerase chain reaction-high performance ion exchange liquid
      chromatographic method for the detection of fibroblast growth factor-beta (FGF
      beta) gene amplification.
AB  - A method for the quantitative determination of fibroblast growth factor-beta (FGF
      beta) genomic amplification based on the use of optimized polymerase chain
      reaction (PCR) procedures and high performance ion exchange (HPIEX) liquid
      chromatography has been developed. Co-amplification of a second genomic species
      permits internal standardization of the techniques during optimization of the
      reaction conditions, the PCR cycle number and the PCR cycle efficiency, as well
      as during the analytical HPIEX chromatographic determination of the PCR products.
      These investigations confirm the versatility of these procedures to
      quantitatively analyse FGF-beta gene amplification in various cells and tissues.

PMID- 1373164
TI  - An autoimmuno-dominant thyroglobulin epitope characterized by a monoclonal
      antibody.
AB  - It has become evident in recent years that autoimmune thyroglobulin (Tg)
      antibodies of Graves disease and Hashimoto's thyroiditis show a restricted
      epitope repertoire compared to Tg heteroantibodies. We have produced monoclonal
      antibodies (Mab) against human Tg by the hybridoma technique and the epitope
      specificity was determined by crossblocking experiments. Six noncrossreactive
      Mabs were used in a double determinant IRMA system for plasma Tg measurements.
      Sensitivity of the assays was between 1 and 2 ng/ml, intraassay variation less
      than 5%. Recovery experiments with added Tg were performed in 25 Graves sera with
      elevated Tg autoantibodies. Monoclonal antibody Tg13 showed an unusual strong
      interference with autoantibodies resulting in a very low recovery in all sera
      (median: less than 10%). In further studies Tg was digested by trypsin and after
      Western blotting, the resulting fragments were incubated with different Mab
      antibodies, a polyclonal antibody and 10 different Graves sera with high Tg
      autoantibodies. In contrast to all other mabs only Mab Tg13 showed several low
      molecular weight bands between 17 and 50 KD. The major bands recognized by Mab
      Tg13 corresponded to bands obtained by the autoimmune sera, which showed a very
      homogeneous band pattern. We conclude that Mab Tg13 is specific for an
      autoimmunodominant B cell epitope of human Tg.

PMID- 1373165
TI  - Regulation of adhesion molecule expression by CD8 T cells in vivo. I.
      Differential regulation of gp90MEL-14 (LECAM-1), Pgp-1, LFA-1, and VLA-4 alpha
      during the differentiation of cytotoxic T lymphocytes induced by allografts.
AB  - A variety of adhesion molecules regulate the traffic and tissue localization of
      lymphocytes in vivo by mediating their binding to vascular endothelial cells. The
      homing receptor gp90MEL-14 (gp90), also known as LECAM-1 or L-selectin, mediates
      the adhesion of lymphocytes to specialized high endothelial venules in lymph
      nodes (LN) and is the primary molecule regulating lymphocyte recirculation and
      homing to LN, whereas other adhesion molecules have a major role in the
      localization of lymphocytes in inflammatory sites. We used four-color flow
      cytometric analysis to examine the regulation of adhesion receptor expression on
      LN CD8 T cells responding to skin allografts in vivo. In normal mice, greater
      than 95% of LN CD8 T cells are gp90+, being either gp90+Pgp1- (Population (Pop.)
      1 or gp90+Pgp-1+ (Pop.2). Allografting induces the down-regulation of gp90 and up
      regulation of Pgp-1 on a subset of cells, resulting in the appearance of CD8+gp90
      Pgp-1hi (Pop. 3) cells. Pop. 3 cells also express high levels of LFA-1, ICAM-1,
      and ICAM-2, and a subset of them are VLA-4 alpha-positive. Purified Pop. 3 cells
      have potent cytolytic activity directed against donor alloantigen, whereas no
      such activity is present in Pop. 1 or 2 cells. Correlating with this is the high
      granzyme activity in Pop. 3 cells. In addition, Pop. 3 lymphocytes, but not Pop.
      1 or 2, secrete a large amount of IFN-gamma in response to Ag. Finally, the CD8 T
      cells that infiltrate sponge matrix allografts are markedly enriched for the Pop.
      3 subset. These results show that, during the immune response to alloantigen in
      vivo, a small subset of CD8 T cells down-regulates the LN homing receptor while
      increasing the expression of other adhesion molecules, as they differentiate into
      highly active cytolytic T lymphocytes. Thus, the differential regulation of LN
      homing receptors and receptors for peripheral vascular endothelium provides a
      mechanism that would redirect the traffic of activated effector cells away from
      lymphoid tissue and to sites of Ag deposition, where they would participate in
      the inflammatory response.

PMID- 1373166
TI  - Saponin adjuvant induction of ovalbumin-specific CD8+ cytotoxic T lymphocyte
      responses.
AB  - The ability of a saponin adjuvant, QS-21, to induce OVA-specific, class I MHC Ag
      restricted CTL was investigated using different forms of soluble OVA and OVA
      adsorbed onto alum as immunogens. C57BL/6 mice were immunized with soluble native
      or denatured OVA in formulations that contained increasing quantities of QS-21,
      and CTL responses were measured using EL4 and E.G7-OVA cells as targets and
      splenic mononuclear cells as effectors. Ag-specific CTL responses were produced
      but only if the QS-21 adjuvant was used. Similar responses were induced using
      alum-adsorbed OVA when mixed with the QS-21 adjuvant but not when used alone. The
      CTL were specific for an epitope present on the OVA258-276 synthetic peptide,
      which contains the dominant CTL epitope recognized by C57BL/6 mice. The CD8+
      subpopulation of lymphocytes in immune mice was not increased in spleens but
      increased significantly in vitro after culture with soluble OVA. The CTL activity
      of splenic mononuclear cell preparations was totally destroyed by treatment with
      mAb specific to the CD8 Ag plus complement. The ability of the QS-21 adjuvant to
      induce class I MHC Ag-restricted CTL after immunization with soluble proteins is
      a characteristic unique to saponin adjuvants.

PMID- 1373167
TI  - E-selectin (endothelial-leukocyte adhesion molecule-1) is not required for the
      migration of neutrophils across IL-1-stimulated endothelium in vitro.
AB  - Treatment of vascular endothelial cells with inflammatory cytokines stimulates
      surface expression of E-selectin (previously known as endothelial-leukocyte
      adhesion molecule-1) and promotes the transendothelial migration of neutrophils.
      To assess participation of E-selectin in cytokine-mediated neutrophil migration,
      an in vitro model consisting of monolayers of human umbilical vein endothelial
      cells (HUVEC) grown on amniotic connective tissue was used. When HUVEC-amnion
      cultures were stimulated for 4 h with relatively low concentrations of IL-1 (0.1
      to 0.15 U/ml), mAb BB11 or H18/7 to E-selectin partially inhibited migration of
      subsequently added neutrophils. However, when the cultures were stimulated with
      15 U/ml of IL-1 for 4 or 24 h, little to no inhibition was observed. mAb to E
      selectin also failed to inhibit migration of neutrophils across HUVEC-amnion
      cultures treated with low doses of IL-1 when the leukocytes were additionally
      stimulated by the chemoattractant leukotriene B4. In contrast, migration of
      neutrophils across IL-1-treated HUVEC was profoundly inhibited by mAb to
      CD11/CD18 leukocytic integrins under all conditions tested. Results of these
      studies suggest that participation of E-selectin is not essential for migration
      of neutrophils across cytokine-stimulated HUVEC in vitro; rather, E-selectin can
      be bypassed in favor of CD11/CD18-dependent mechanisms under appropriate
      circumstances.

PMID- 1373168
TI  - IL-4 induces conformational change of CD20 antigen via a protein kinase C
      independent pathway. Antagonistic effect of anti-CD40 monoclonal antibody.
AB  - The CD20 molecule is a unique phosphoprotein exclusively expressed on B cells
      during most stages of B cell ontogeny. We here report that rIL-4 down-regulates
      the expression of CD20 with anti-Leu-16 mAb (clone L27) on both unstimulated and
      anti-mu preactivated normal and leukemic B cells. None of the other recombinant
      lymphokines tested (IL-1, IL-2, IL-3, IL-6, IFN-alpha, and IFN-gamma,
      granulocyte/macrophage-CSF, transforming growth factor-beta, TNF-alpha, and
      lymphotoxin) decreased CD20 expression. Incubation of unstimulated or anti-mu
      preactivated B cells with IL-4 did not affect the steady state CD20 mRNA,
      suggesting that IL-4 exerted its effect mainly at a nontranscriptional level.
      Hence, IL-4 selectively down-regulates the CD20 epitope recognized by clone L27
      without affecting seven other different epitopes, indicating that IL-4 acts by
      modifying the conformation of the CD20 molecule rather than by inhibiting its
      production or inducing its internalization. IL-4 most likely utilizes a protein
      kinase C-independent signal transduction pathway to modify CD20 molecule inasmuch
      as staurosporine, an inhibitor of protein kinase C, antagonizes phorbol esters
      (PMA) but not IL-4-induced CD20 down-regulation. In contrast, anti-CD40 mAb
      reverses the IL-4 but not the PMA inhibitory effect on CD20 expression. Given
      that CD20 may be part of a Ca2+ ion channel and plays a role in B cell activation
      and proliferation, it is proposed that the ability of anti-CD40 mAb to maintain
      the CD20 molecule in a given epitopic configuration on IL-4-stimulated B cells
      may be related to the long term proliferation of normal B cells that are strictly
      dependent on the presence of IL-4 and cross-linked anti-CD40 mAb for their
      continuous growth.

PMID- 1373169
TI  - A comparative study of IL-12 (cytotoxic lymphocyte maturation factor)-, IL-2-,
      and IL-7-induced effects on immunomagnetically purified CD56+ NK cells.
AB  - IL-12, or cytotoxic lymphocyte maturation factor, is a recently cloned cytokine
      shown to influence lymphokine-activated killer cells activity in heterogeneous
      lymphocyte populations, proliferative activity as a costimulus in PBMC/PBL
      populations and IFN-gamma production in PBL. We have investigated the effects of
      IL-12 on immunomagnetically highly purified CD56+ lymphocytes, and compared the
      effects with those of IL-7 and IL-2. Our results show that IL-12 directly
      generated high lymphokine-activated killer cell activity in CD56+ NK cells,
      without the need for accessory cells. The IL-12-induced lymphokine-activated
      killer cell activity reached 50% of what was obtained with IL-2. In contrast,
      only low proliferative activity was induced by IL-12, as 10% of the IL-2-induced-
      and approximately 50% of the IL-7-induced proliferative activity was detected
      with IL-12. The CD56+ cells expressed high levels of IL-2R alpha and 75-kDa TNFR
      in response to IL-12, comparable to what was registered with IL-2 and IL-7.
      Furthermore, an extensive up-regulation of the CD56 Ag, to the level obtained
      with IL-2, was detected in the CD56+ NK cells in the presence of IL-12.
      Stimulation with IL-7 resulted in a more limited CD56 up-regulation in the CD56+
      NK cells. Low concentrations of TNF-alpha were produced in response to both IL-12
      and IL-7, with little or no TNF-beta production. Time course of the IL-2-induced
      TNF production revealed an initial TNF-alpha production, whereas significant
      levels of TNF-beta were detected after 72 h. The effects of both IL-12 and IL-7
      on the CD56+ NK cells were inhibited by an anti-TNF-alpha mAb. Thus, IL-12 can
      directly influence NK cell activities in purified CD56+ cells, and endogenously
      produced TNF-alpha is involved in mediating the effects of both IL-12 and IL-7.

PMID- 1373171
TI  - In vivo binding and clearance of circulating antigen by bispecific heteropolymer
      mediated binding to primate erythrocyte complement receptor.
AB  - We have used the avidin/biotin system to construct soluble, cross-linked
      bispecific heteropolymers containing mAb to both the primate E C receptor and the
      DNP group. These heteropolymers facilitate in vitro binding of DNP-bovine gamma
      globulin (DNP-BGG) to both human and squirrel monkey E. Intravenous injection in
      squirrel monkeys of DNP-BGG followed by heteropolymer leads to E binding and
      clearance from the circulation of a significant fraction of both heteropolymer
      and DNP-BGG, without lysis or clearance of the E. This methodology may
      potentially be used to treat a variety of infectious diseases and other syndromes
      associated with blood-borne pathogens.

PMID- 1373170
TI  - A mechanism of action for anaphylatoxin C3a stimulation of mast cells.
AB  - Incubation of either C3a, C3ades Arg, or synthetic analogues of the C-terminal
      sequence of C3a with purified rat peritoneal mast cells resulted in a rapid and
      dose-dependent histamine release. The natural factors C3a and C3ades Arg were the
      most active of the factors tested exhibiting EC50 values of 3.3 and 2.2 microM,
      respectively. The corresponding 21- and 22-residue C-terminal analogues of C3a
      (Y21R and Y21) were less potent than intact factor exhibiting EC50 values of 10.9
      and 25.1 microM, respectively. Histamine was released in a nonlytic manner and
      the mast cell stimulation by both natural and synthetic factors was sensitive to
      pertussis toxin, neuraminidase, benzalkonium chloride, and to an excess of
      calcium. C3a stimulated the generation of inositol polyphosphates that was
      inhibited by either pertussis toxin or benzalkonium chloride. The C3a
      anaphylatoxin also directly stimulates purified G proteins (i.e., GTPase
      activity) in a dose-dependent manner. The evident correlation between efficiency
      of C3a and C3a analogues to stimulate purified G proteins and their capacity to
      induce cellular histamine release led us to conclude that C3a fails to activate
      mast cells via a mechanism involving specific receptors on the cell. Instead, we
      propose that C3a either causes direct activation of G proteins of the Gi subtype,
      with a subsequent activation of phospholipase C, or interacts with a binding site
      of the cell surface specific for cationic molecules that is coupled to the G
      protein cascade.

PMID- 1373172
TI  - Preliminary identification and role of phosphodiesterase isozymes in human
      basophils.
AB  - We attempted to identify and establish the role of cyclic nucleotide
      phosphodiesterase (PDE) isozymes in human basophils by using standard biochemical
      techniques as well as describing the effects of isozyme-selective and
      nonselective inhibitors of PDE. The nonselective PDE inhibitors, theophylline and
      3-isobutyl-1-methylxanthine, inhibited anti-IgE-induced release of histamine and
      leukotriene C4 (LTC4) from basophils. This inhibition was accompanied by
      elevations in cAMP levels. Rolipram, an inhibitor of the low Km cAMP-specific PDE
      (PDE IV), inhibited the release of both histamine and LTC4 from activated
      basophils and increased cAMP levels in these cells. In contrast, mediator release
      from basophils was not inhibited by either siguazodan or SK&F 95654, inhibitors
      of the cGMP-inhibited PDE (PDE III) or zaprinast, an inhibitor of the cGMP
      specific PDE (PDE V). SK&F 95654 failed to elevate basophil cAMP in these
      experiments whereas zaprinast induced significant increases in cAMP content. The
      inhibitory effect of rolipram on mediator release was potentiated by siguazodan
      or SK&F 95654, but not by zaprinast. SK&F 95654 also enhanced the ability of
      rolipram to increase cAMP content. Forskolin, a direct activator of adenylate
      cyclase, inhibited IgE-dependent release of mediators from basophils and
      increased cAMP levels in these cells. These effects were enhanced by rolipram,
      but not by SK&F 95654 or zaprinast. The cell permeant analog of cAMP, dibutyryl
      cAMP, inhibited mediator release from these cells, a property not shared by
      either dibutyryl-cGMP or sodium nitroprusside, an activator of soluble guanylate
      cyclase. The presence of both PDE III and PDE IV was confirmed by partially
      purifying and characterizing PDE activity in broken cell preparations. Overall,
      these data lend support to the hypothesis that cAMP inhibits mediator release
      from basophils and suggest that the major PDE isozyme responsible for regulating
      cyclic AMP content in these cells is PDE IV, with a minor contribution from PDE
      III. However, the finding that zaprinast caused increases in cAMP without
      inhibiting mediator release indicates that cAMP accumulation is not invariably
      linked to an inhibition of basophil activation.

PMID- 1373173
TI  - The antigen-processing mutant T2 suggests a role for MHC-linked genes in class II
      antigen presentation.
AB  - .174xCEM.T2 (T2) is a human cell hybrid that has a large homozygous deletion
      within the MHC, including all of the functional class II genes. We have generated
      stable HLA-DR3 and H-2 I-Ak transfectants of T2 that express parental levels of
      class II molecules at the cell surface. T2.Ak transfectants fail to stimulate a
      hen egg lysozyme (HEL)-specific, I-Ak-restricted T cell when incubated with
      intact HEL. However, stimulation occurs if the appropriate HEL peptide is
      provided. The T2 cell line therefore has a defect in class II-restricted Ag
      processing. Biosynthetic studies demonstrate that the kinetics of I-Ak transport
      in T2.Ak are similar to the parental rates of transport, although the percentage
      of I-Ak molecules transported appears somewhat lower. I-Ak glycoproteins in T2.Ak
      associate normally with the I-chain, which appears to be proteolytically cleaved
      after transport through the Golgi apparatus in a similar fashion to that in the
      parent cell line, .174xCEM.T1 (T1). The DR alpha beta heterodimers in T2 differ
      from the parental phenotype in two ways. First, HLA-DR3 expressed in T2 does not
      have the epitope recognized by the DR3-specific mAb 16.23, although DR3 expressed
      in the parent does have the epitope. Second, the alpha beta subunits in the
      parent remain associated when exposed to SDS at room temperature, although those
      in T2 dissociate.

PMID- 1373174
TI  - Age-dependent changes in the oligosaccharide structure of the major myelin
      glycoprotein, P0.
AB  - The single oligosaccharide moiety of the major myelin glycoprotein, P0, resides
      in an immunoglobulin-like domain that appears to participate in homophilic
      binding. The studies presented here indicate that the structure of the P0
      oligosaccharide from rat nerve changes as a function of Schwann cell age.
      Examination of 5-day-old nerve revealed that P0 contained predominantly endo-beta
      N-acetylglucosaminidase H (endo H)-resistant, complex-type oligosaccharide. In
      contrast, P0 from adult rats had mostly endo H-sensitive carbohydrate, indicating
      the presence of appreciable high-mannose and/or hybrid-type oligosaccharide on
      the glycoprotein. The endo H-sensitive and -resistant P0 of adult nerve could be
      readily phosphorylated by protein kinase C, as could the complex-type P0 from 5
      day-old nerve. This suggests that the glycoprotein progresses to the plasma
      membrane and myelin regardless of the type of oligosaccharide chain. Analysis of
      35SO4(2-)-labeled P0 showed that the sulfate group was found on both endo H
      sensitive and -resistant oligosaccharide. The endo H-sensitive P0 carbohydrate
      from adult nerve appears to be primarily of the hybrid type, as evidenced by (a)
      the elution profile of [3H]mannose-labeled P0 glycopeptides from adult nerve
      during concanavalin A chromatography and (b) the inability of P0 from adult nerve
      to interact with Galanthus nivalis agglutinin. The observed age-dependent changes
      of P0 oligosaccharide may modify the binding properties of this myelin
      glycoprotein.

PMID- 1373175
TI  - Purification and partial structural and functional characterization of mouse
      myelin/oligodendrocyte glycoprotein.
AB  - The myelin/oligodendrocyte glycoprotein (MOG) is found exclusively in the CNS,
      where it is localized on the surface of myelin and oligodendrocyte cytoplasmic
      membranes. The monoclonal antibody 8-18C5 identifies MOG. Several studies have
      shown that anti-MOG antibodies can induce demyelination, thus inferring an
      important role in myelin stability. In this study, we demonstrate that MOG
      consists of two polypeptides, with molecular masses of 26 and 28 kDa. This
      doublet becomes a single 25-kDa band after deglycosylation with
      trifluoromethanesulfonic acid or peptide-N4-(N-acetyl-beta
      glucosaminyl)asparagine amidase, indicating that there are no or few O-linked
      sugars and that the doublet band represents differential glycosylation. Partial
      trypsin cleavage, which also gave a doublet band of lower molecular weight,
      confirmed this idea. MOG was purified by polyacrylamide gel electrophoresis,
      followed by electroelution. Three N-terminal sequences of eight to 26 amino acids
      were obtained. By western blot analysis, no binding was found between MOG and
      cerebellar soluble lectin. MOG does not seem to belong to the signal-transducing
      GTP-binding proteins. Reduced MOG concentrations were observed in jimpy and
      quaking dysmyelinating mutant mice, giving further support to its localization in
      compact myelin of the CNS.

PMID- 1373176
TI  - On the use of multiple probe insertions at the same site for repeated
      intracerebral microdialysis experiments in the nigrostriatal dopamine system of
      rats.
AB  - The effects of implantation of a dialysis probe into the striatum of awake rats
      on indices of dopamine (DA) and serotonin neurotransmission were assessed, first
      over 24 h following initial insertion of a probe, and then again following
      reinsertion of a probe at the same site 1 week later. It was found that the basal
      concentration of DA in dialysate stabilized within 20-40 min after probe
      implantation, although DA showed a modest decline 24 h later. There was, however,
      no significant difference in basal DA between two test sessions separated by 1
      week. On the other hand, the basal concentrations of the DA metabolites, 3,4
      dihydroxyphenylacetic acid and homovanillic acid, progressively increased for 2-3
      h after probe implantation and decreased markedly by 24 h later. Furthermore, in
      contrast to DA, the DA metabolites decreased even further after the second probe
      insertion. Amphetamine-stimulated DA release was also greatly attenuated
      following the second probe insertion, relative to the first probe insertion. Two
      probe insertions had only modest effects on the concentration of 5
      hydroxyindoleacetic acid in dialysate, relative to the DA metabolites. It is
      suggested the effects of two probe insertions on DA metabolism and amphetamine
      stimulated DA release described here are indicative of probe-induced damage to
      the nigrostriatal DA system. If this is the case, multiple probe insertions may
      not provide a feasible strategy for within-subjects design dialysis experiments
      over extended periods of time, at least in the DA system of small animals. It is
      suggested further that a stable basal concentration of DA in dialysate may be an
      especially poor indicator of the integrity of the dopaminergic input to the
      striatum.

PMID- 1373177
TI  - Properties of muscarinic-stimulated adenylate cyclase activity in rat olfactory
      bulb.
AB  - The muscarinic stimulation of adenylate cyclase activity in rat olfactory bulb
      was characterized, with the aim of elucidating the nature of the molecular
      mechanism involved. Carbachol (CCh) stimulated the enzyme activity in either
      crude or purified cell membrane preparations and increased cyclic AMP
      accumulation in miniprisms of olfactory bulb. The CCh stimulation of adenylate
      cyclase activity displayed a fast onset and was rapidly reversed by addition of
      atropine. The stimulation was associated with an increase in the apparent Vmax of
      the enzyme, with no change in the Km for Mg-ATP. The affinity of the enzyme for
      Mg2+ was enhanced by CCh. The muscarinic effect required GTP at concentrations
      higher than those needed for enzyme stimulation with either l-isoproterenol or
      vasoactive intestinal peptide. Moreover, contrary to the beta-adrenergic
      stimulation, the muscarinic effect disappeared when guanosine 5'-O-(3'
      thiotriphosphate) was substituted for GTP. In vivo treatment of olfactory bulbs
      with pertussis toxin completely prevented the muscarinic stimulation of adenylate
      cyclase, whereas cholera toxin was without effect. These results indicate that in
      rat olfactory bulb muscarinic receptors increase adenylate cyclase activity by
      interacting with a pertussis toxin-sensitive GTP-binding protein different from
      the stimulatory GTP-binding protein.

PMID- 1373178
TI  - A rabbit autoantibody specific for the 46-kDa form of 2',3'-cyclic nucleotide 3'
      phosphodiesterase.
AB  - An autoantibody occurring in the serum of an apparently normal rabbit that
      immunocytochemically stains myelin sheaths and oligodendrocytes in rat brain was
      shown to react specifically with the 46-kDa isoform of 2',3'-cyclic nucleotide 3'
      phosphodiesterase (CNP) (EC 3.1.4.37) in a number of species. Identification of
      the shorter isoform of the enzyme (CNP1) as the antigen was achieved by comparing
      the immunostaining of Western blots by the autoantibody with that of a well
      characterized anti-CNP antiserum. The 46-kDa antigen reacting with the
      autoantibody exhibited the same Mr and pI as the small isoform of CNP on two
      dimensional gels and showed a similar enrichment in purified CNS myelin. The
      autoantibody has very high affinity for CNP1 and is capable of detecting the very
      low amounts of this enzyme in peripheral nerve, spleen, adrenal gland, pancreas,
      testis, and intestine. Testing the reactivity of the autoantibody with synthetic
      peptides by enzyme-linked immunosorbent assay revealed that it reacted with the N
      acetylated decapeptide corresponding to the N-terminus of CNP1, but did not react
      if the peptide was not acetylated or if the acetyl group was replaced with a
      palmityl group. The lack of reactivity with CNP2, which differs from CNP1 by a 20
      amino acid extension at the N-terminus of the protein as a result of alternative
      splicing, may be due to the absence of the N-acetyl moiety that is part of the
      epitope and/or blocking of antibody binding to the decapeptide by extension of
      the polypeptide chain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373179
TI  - Decreased density of presynaptic alpha 2-adrenoceptors in postmortem brains of
      patients with Alzheimer's disease.
AB  - The full agonist [3H]bromoxidine (UK 14304) was used to quantitate alpha 2
      adrenoceptors in postmortem brains of patients with Alzheimer's disease. The
      effects of aging and human serum Cohn fraction IV on [3H]bromoxidine binding were
      also assessed. In patients with Alzheimer's disease, the binding capacity (Bmax)
      of [3H]bromoxidine was lower in the frontal cortex (37%), hypothalamus (33%), and
      cerebellum (52%) than in matched controls. In the hippocampus, amygdala, and head
      of caudate, the binding capacities (Bmax) were unchanged. Quantitative
      autoradiographic analyses with [3H]bromoxidine confirmed the existence of a
      marked reduction (55-60%) in alpha 2A-adrenoceptor density in the frontal cortex
      (layers I and III). In patients with dementia who did not meet neuropathological
      criteria for Alzheimer's disease, the density of alpha 2-adrenoceptors was
      unchanged. In control subjects, the density of alpha 2A-adrenoceptors in the
      frontal cortex showed a significant negative correlation with age at death. The
      inhibitory effect of human serum Cohn fraction IV on [3H]bromoxidine was very
      similar in control subjects and patients with Alzheimer's disease. The observed
      decrease in the density of brain alpha 2-adrenoceptors in Alzheimer's disease may
      represent direct biochemical evidence of a presynaptic location of this receptor
      on noradrenergic nerve terminals in the human CNS.

PMID- 1373180
TI  - Estrogen induction of cytochrome c oxidase subunit III in rat hippocampus.
AB  - Differential screening of a cDNA library prepared from mRNA of the hippocampus of
      estrogen-stimulated ovariectomized female rats led to the identification of a
      single estrogen-induced clone. Analysis of the sequence identified this cDNA as
      the gene coding for subunit III of the enzyme cytochrome c oxidase. Cytochrome c
      oxidase subunit III mRNA levels significantly increased as early as 3 h following
      the administration of a single dose of hormone. This effect was visible in the
      hippocampus and in the hypothalamus, but not in the other brain areas examined.
      Because subunit III of the cytochrome c oxidase is of mitochondrial origin, the
      mechanism involved in the estrogenic effect is still unknown. The observation
      that the activity of cytochrome c oxidase can also be induced by estrogens in the
      hippocampus indicates that this induction may be secondary to the increased
      expression of the other subunits of cytochrome c oxidase or to the general
      increase of neuronal activity.

PMID- 1373181
TI  - Detergent-insoluble cortical Lewy body fibrils share epitopes with neurofilament
      and tau.
AB  - Lewy bodies are cytoskeletal inclusions associated with neuronal injury and death
      in idiopathic Parkinson's disease and other neurodegenerative disorders. The
      chemical composition of the 8-10-nm fibrils of the Lewy body is unknown, although
      they are related to both normal cytoskeletal elements and paired helical
      filaments of Alzheimer neurofibrillary tangles. From the Lewy body-rich cerebral
      cortex of patients with diffuse Lewy body disease we have isolated intact Lewy
      bodies using a high salt buffer/nonionic detergent gradient centrifugation
      procedure and extracted the constitutive fibrils with urea and sodium dodecyl
      sulfate. Urea/detergent-resistant Lewy body fibrils were solubilized with formic
      acid and found to contain a single protein band of 68 kDa, which was not found in
      identically prepared normal brain homogenates. The Lewy body derived-polypeptide
      was recognized on immunoblots by a polyclonal antibody that reacted with both the
      68-kDa neurofilament subunit and the microtubule-associated protein tau. The 68
      kDa Lewy body protein was not labeled by the monoclonal antibody tau-1 despite
      prior in vitro enzymatic dephosphorylation. We conclude that the detergent
      insoluble component of the cortical Lewy body fibril shares epitopes with
      neurofilament and tau and may be a posttranslationally modified derivative of
      either neurofilament or tau with substantially altered biochemical and
      immunologic properties.

PMID- 1373182
TI  - Localization of actin in the retina of the crayfish Procambarus clarkii.
AB  - The distribution of actin in the retina of the crayfish was investigated at the
      LM level using FITC-phalloidin. Fluorescent staining was associated with the main
      rhabdom and eighth cell rhabdom, the zonula adherens junctions between retinula
      cells, and the basement membrane of the retina. EM and S1 decoration were used to
      confirm the presence of actin and identify its structural relationships.
      Phalloidin staining of the rhabdom and S1 decoration of actin filaments in the
      rhabdom microvilli confirmed earlier findings that actin is a component of the
      microvillus cytoskeleton in the crayfish. At the zonula adherens junctions, actin
      filaments, identified by S1 decoration, run longitudinally within the plaque of
      the junction. At the extreme proximal end of the rhabdom, actin filaments
      associated with the junctions fill each small area of retinula cell cytoplasm. In
      the basement membrane, EM and S1 decoration show that basilar cells contain large
      bundles of actin filaments which are associated with cell-matrix adherens
      junctions. Foot cells which lie immediately below the rhabdom also contain
      similar junctions and actin is tentatively identified in these cells. The
      functional role of actin at these various locations is discussed in relation to
      retinal organization in the crayfish and other invertebrates.

PMID- 1373183
TI  - BUdR as an S-phase marker for quantitative studies of cytokinetic behaviour in
      the murine cerebral ventricular zone.
AB  - BUdR incorporation into replicating DNA, detected immunohistochemically, is used
      as an S-phase marker in the proliferative cell populations of the cerebral wall
      of the mouse embryo on the 14th gestational day (E14). The analysis initiates a
      series of studies concerned with the cytokinetic behaviour and cell output of
      proliferative populations involved in neocortical histogenesis. On E14 there are
      two periventricular proliferative zones in the cerebral wall. These are the
      ventricular and subventricular zones. The ventricular zone is a pseudostratified
      epithelium. DNA replication occurs with the cell nucleus in the outer zone of the
      epithelium and mitoses at the ventricular surface. Prior applications of BUdR for
      studies of cytogenesis in the CNS have been extended in two principal ways: (1)
      basic fuchsin was used as counterstain for BUdR-negative nuclei and (2) labelling
      indices were determined separately in strata or bins, 10 microns in height,
      through the full depth of the ventricular zone and overlying cerebral wall. It
      was established that a single injection of 50 micrograms g-1 into the pregnant
      dam was associated with labelling of 100% of nuclei in S-phase over an interval
      extending from 15 min to at least 2.0 h after injection. The zone where nuclei
      are undergoing S-phase (S-phase zone) extends through the outer four bins of the
      ventricular zone. The method has high quantitative reproducibility with an SE for
      labelling indices in bins within the S-phase zone less than 10% of the average
      values. Evidence is provided that BUdR incorporation is initiated with the
      nucleus in the outer aspect of the S-phase zone. The efficiency of incorporation
      of the marker is reduced as nuclei near the end of DNA replication and move to
      the inner aspect of the S-phase zone.

PMID- 1373184
TI  - Phosphorylation-dependent neurofilament epitopes are reduced at the node of
      Ranvier.
AB  - Neurofilaments in axons are highly phosphorylated at multiple sites on the 200
      kDa neurofilament (neurofilament-H) and 160 kDa (neurofilament-M) subunit
      peptides. We used a panel of monoclonal and polyclonal antibodies against
      distinct neurofilament epitopes to study the distribution of these epitopes along
      the axons of large myelinated fibres in rat sciatic nerve using quantitative
      electron microscopic immunocytochemistry with colloidal gold. Antibodies specific
      for phosphorylated epitopes on neurofilament-H showed a 60% reduction in density
      of immunoreactivity at the node of Ranvier, compared to the internodal axon.
      Antibodies directed against neurofilament-M, which recognized phosphorylated
      epitopes preferentially, showed a 40% reduction in density of immunoreactivity at
      the node. Following dephosphorylation of the neurofilaments in tissue sections by
      alkaline phosphatase treatment, antibodies which recognized dephosphorylated
      forms of neurofilament-H showed no reduction in density of immunoreactivity at
      the node. Similarly, an antibody directed against the 70 kDa subunit
      (neurofilament-L), showed no reduction in density of immunoreactivity at the
      node. An antibody against tubulin also showed no decrease in the density of
      immunoreactivity at the node of Ranvier. Tubulin immunoreactivity was similar in
      myelinated and unmyelinated fibres. In contrast to phosphorylated neurofilament
      epitopes, immunoreactivity was much greater in myelinated than unmyelinated
      fibres. These results suggest that the degree of phosphorylation of neurofilament
      H and neurofilament-M subunits is reduced at the node of Ranvier, in comparison
      to internodal neurofilaments, and imply that a post-translational modification of
      neurofilaments must occur along the length of the axon at the node.

PMID- 1373185
TI  - Factors leading to nurse empowerment.

PMID- 1373186
TI  - A search for Pneumocystis carinii in post-mortem lungs by DNA amplification.
AB  - DNA amplification of specific sequences and subsequent oligonucleotide
      hybridization were used to search for Pneumocystis carinii in post-mortem lung
      samplings from non-immunosuppressed individuals ranging from 15 to 70 years of
      age. No P. carinii-specific DNA was detected in 45 DNA amplification reactions
      from 15 lungs.

PMID- 1373187
TI  - Rapid acinar to ductal transdifferentiation in cultured human exocrine pancreas.
AB  - Experiments have been performed to define conditions for the primary culture of
      human exocrine pancreas, as a first step towards molecular reconstruction
      experiments of pancreatic neoplasia. Normal human exocrine pancreas was digested
      using collagenase and dispase and the resulting cellular aggregates were cultured
      in vitro. The phenotype of the digested pancreatic cells was almost exclusively
      acinar (amylase-positive, keratin 19 and mucin antigens-negative), yet within 4
      days of culture the cells had taken on a ductal phenotype (amylase-negative,
      keratin 19 and mucin antigens-positive). The kinetics of these observations
      exclude the possibility of overgrowth of the acinar population by a ductal sub
      population, and selective adherence is excluded by examination of those cells
      that do not adhere, which are representative of the initiating population. We
      interpret these data as indicating that, under the conditions of culture, the
      acinar cell phenotype is not stable and can transdifferentiate to a ductal
      phenotype. Taken together with recent data from transgenic animals, this in vitro
      observation has possible implications for our view of the pathogenesis of
      pancreatic neoplasia.

PMID- 1373188
TI  - Role of the gamma-aminobutyric acid receptor/chloride channel complex in
      tolerance to ethanol and cross-tolerance to diazepam and pentobarbital.
AB  - The role of the gamma-aminobutyric acid (GABA) receptor/chloride channel complex
      in the development of tolerance to ethanol and cross-tolerance to diazepam and
      pentobarbital was assessed. Rats given a low (1.8 g/kg) dose of ethanol before
      daily practice on the moving belt test of motor incoordination, and those given a
      high daily dose (3.6 g/kg) not paired with practice, showed tolerance to ethanol
      and cross-tolerance to diazepam and pentobarbital, whereas rats receiving 1.8
      g/kg of ethanol after practice did not. Control rats were trained on the moving
      belt, but received no ethanol treatment. No differences were seen among the
      treatment groups in the abilities of GABA or ethanol to increase 36Cl uptake into
      cerebral cortical microsacs. However, diazepam potentiation of GABA-mediated
      chloride flux was significantly lower in rats receiving daily intoxicated
      practice, but only if they received an i.p. injection of ethanol 1 hr before
      sacrifice. The degree of pentobarbital potentiation of the effect of GABA did not
      correlate with the behavioral cross-tolerance observed. The results indicate that
      behaviorally augmented cross-tolerance from ethanol to diazepam correlates
      incompletely with changes on the biochemical level.

PMID- 1373189
TI  - Discrimination of agonist-antagonist opioids in humans trained on a two-choice
      saline-hydromorphone discrimination.
AB  - The stimulus properties of four opioid agonist-antagonists were assessed in
      postaddict volunteers trained in a two-choice drug discrimination procedure to
      discriminate between the effects of i.m. saline and hydromorphone (3 mg/70 kg).
      Behavioral, subjective and physiological measures were concurrently collected.
      After training, generalization curves were determined for hydromorphone,
      pentazocine, butorphanol, nalbuphine and buprenorphine. In generalization
      testing, hydromorphone produced dose-related increases in hydromorphone
      appropriate responses and in characteristic opioid agonist-like subjective
      effects measures. In general, each of the study drugs produced a profile of
      subjective and physiological effects similar to that reported in other human
      studies. These subjective indices showed the study drugs to be heterogeneous.
      However, in this two-choice drug discrimination procedure, they were
      discriminated as homogeneous (i.e., all were discriminated as hydromorphone
      like). The present study also found that all test drugs were subjectively
      identified as being opiates, and all were subjectively rated as similar to the
      hydromorphone training condition. A previous three-choice discrimination was
      sensitive to the heterogeneity among these drugs on both the discrimination
      measures and subjective ratings of similarity to the hydromorphone training
      condition. Thus, the specific procedures of drug discrimination studies may have
      an effect on some subjective indices, although this interaction is not apparent
      for the majority of subjective effect measures. Also, the characterization of
      opioids in drug discrimination testing appears to depend upon the specific
      training subjects receive; this is most clear with discrimination measures, and
      to a more limited extent, with subjective measures.

PMID- 1373190
TI  - Synthesis, characterization, and anti-human immunodeficiency virus activity of
      water-soluble salts of polyoxotungstate anions with covalently attached organic
      groups.
AB  - The cesium and tetramethylammonium (TMA) salts of polyoxotungstate anions with
      covalently attached organosilyl groups of formula [(RSi)2O]SiW11O39(4-), where R
      = CH2CH2COCH3, (CH2)3CN, and CH==CH2 (1-R, cesium salt, unless otherwise noted)
      have been prepared, purified, and spectroscopically characterized. The water
      solubility (25 degrees C) of these 10 new compounds ranges from 0.14 mM to 2.16
      mM. All appear to be stable in aqueous media over a period of several hours as
      assessed by 1H NMR. The activities (EC50) of the new compounds against human
      immunodeficiency virus in primary human lymphocytes range from 3.3 microM to 39.0
      microM. Their toxicities (IC50) are all greater than 100 microM. The inhibition
      constants of the new compounds against purified virion-derived HIV-1 reverse
      transcriptase are in the 1-10 microM range.

PMID- 1373191
TI  - Synthesis and substance P antagonist activity of naphthimidazolium derivatives.
AB  - The synthesis of unsymmetrical naphth[2,3-d]imidazolium and bridged naphth[2,3
      d]imidazolium derivatives and their substance P (SP) antagonist activity are
      described. All compounds were evaluated for their ability to displace SP from
      neurokinin-1 (NK-1) receptor sites using standard receptor binding methodology
      (rat forebrain membrane). 1,3-Diethyl-2-[3-(1,3-dihydro-1,3,3-timethyl-2H-indol-2
      ylidene) -1-propenyl]-1H-naphth[2,3-d]imidazolium chloride (7a), a representative
      compound in this series, was further evaluated for SP antagonist activity in a
      guinea pig ileum contractility assay. In vivo SP antagonist activity of 7a was
      demonstrated using SP-induced salivation and paw edema models performed in rats.

PMID- 1373192
TI  - Amplification of 16S rRNA sequences to detect Mycobacterium paratuberculosis.
AB  - A probe based on 16S ribosomal RNA (rRNA) sequences was developed to detect
      Mycobacterium paratuberculosis, the causative agent of Johne's disease in cattle.
      Three universal primers were used to sequence the amplified fragments of the 16S
      rRNA gene of various species of mycobacteria. When the nucleotide sequences were
      analysed, a deletion was detected in the sequence of the fast-growing species. An
      oligonucleotide probe (P) directed to this region was synthesised and hybridised
      directly with total RNA of various mycobacterial strains in a dot-spot assay. The
      probe detected M. paratuberculosis, some other slow-growing mycobacteria of the
      M. avium-intracellulare (MAI) complex, and one atypical strain, M. gordonae. To
      increase the sensitivity of the probe, a 413-bp fragment of the 16S rRNA gene of
      M. paratuberculosis between P and a second oligonucleotide primer was amplified
      and hybridised with a M. paratuberculosis/M. avium-specific probe. When faecal
      samples of cattle were tested, all culture-positive samples were positive in the
      PCR assay.

PMID- 1373193
TI  - Entero-adherent Escherichia coli is an important diarrhoeagenic agent in infants
      aged below 6 months in Calcutta, India.
AB  - Escherichia coli adherent to HEp-2 and HeLa cells were isolated from the faeces
      of 43 (19.7%) of 218 hospitalised infants aged below 6 months with acute
      diarrhoea. No conventional virulence factors, including enterotoxin production-
      heat-labile (LT) or heat-stable (ST), the verotoxin (VT) or shiga-like toxin
      (SLT)--or the invasive phenotype (determined by the Sereny test) could be
      detected among these isolates. Out of the 43 isolates, 16 (37.2%) were of the
      known enteropathogenic O:K serogroups--enteropathogenic E. coli (EPEC). The
      remaining 27 (62.8%) isolates showed different types of adherence to HEp-2 and
      HeLa cells which was diffuse (40.7%), localised (37.0%), or both (22.3%); they
      were identified as entero-adherent E. coli (EAEC). The EAEC isolates adhered to
      HEp-2 and HeLa cells in the presence of mannose, lactose, fucose, galactose, and
      fetuin, indicating that adhesion was not specific for these sugars or
      glycoprotein. Haemagglutination and the salt aggregation test (SAT) did not
      correlate with patterns of adherence. The results of this study indicate that LA
      EAEC is an important aetiological agent of acute diarrhoea in infants aged below
      6 months in Calcutta.

PMID- 1373194
TI  - Nucleotides of tRNA governing the specificity of Escherichia coli methionyl
      tRNA(fMet) formyltransferase.
AB  - In Escherichia coli, the free amino group of the aminoacyl moiety of methionyl
      tRNA(fMet) is specifically modified by a transformylation reaction. To identify
      the nucleotides governing the recognition of the tRNA substrate by the formylase,
      initiator tRNA(fMet) was changed into an elongator tRNA with the help of an in
      vivo selection method. All the mutations isolated were in the tRNA acceptor arm,
      at positions 72 and 73. The major role of the acceptor arm was further
      established by the demonstration of the full formylability of a chimaeric
      tRNA(Met) containing the acceptor stem of tRNA(fMet) and the remaining of the
      structure of tRNA(mMet). In addition, more than 30 variants of the genes encoding
      tRNA(mMet) or tRNA(fMet) have been constructed, the corresponding mutant tRNA
      products purified and the parameters of the formylation reaction measured.
      tRNA(mMet) became formylatable by the only change of the G1.C72 base-pair into C1
      A72. It was possible to render tRNA(mMet) as good a substrate as tRNA(fMet) for
      the formylase by the introduction of a limited number of additional changes in
      the acceptor stem. In conclusion, A73, G2.C71, C3.G70 and G4.C69 are positive
      determinants for the specific processing of methionyl-tRNA(fMet) by the formylase
      while the occurrence of a G.C or C.G base-pair between positions 1 and 72 acts as
      a major negative determinant. This pattern appears to account fully for the
      specificity of the formylase and the lack of formylation of any aminoacylated
      tRNA, excepting the methionyl-tRNA(fMet).

PMID- 1373195
TI  - Application of staining of nucleolar organizer regions in cytological smears of
      the bronchus.
AB  - An argyrophil technique for the staining nucleolar organizer regions (AgNOR) was
      applied to cytological preparations obtained from bronchoscopic brushing
      materials. The number of AgNOR has been thought to be related to cellular
      activation. To differentiate malignant cells from non-malignant atypical cells,
      this study was carried out in 20 cases of adenocarcinoma of the lung (mean AgNOR:
      18.34), 12 cases of pulmonary inflammatory diseases (mean AgNOR: 6.54) and 10
      normal bronchial epithelial specimens for control (mean AgNOR: 2.07). On the
      basis of AgNOR number, we could differentiate between the three groups. The
      differences observed were statistically highly significant (p less than 0.0001).
      Moreover, the nucleolar organizer regions (NOR) in cancer cells were found the
      more irregularly distributed and more variable in sized than those in atypical
      and normal bronchial columnar cells. We suggest that the AgNOR technique will
      find increasing application as a complementary test in diagnostic cytopathology.

PMID- 1373196
TI  - Sonographic findings in a fetus with congenital nephrotic syndrome of the Finnish
      type.

PMID- 1373197
TI  - Target epitope in the Tax protein of human T-cell leukemia virus type I
      recognized by class I major histocompatibility complex-restricted cytotoxic T
      cells.
AB  - A trans-acting regulatory gene product p40tax (Tax) of human T-cell leukemia
      virus type I (HTLV-I) is one of the main target antigens recognized by cytotoxic
      T lymphocytes (CTL) specific for HTLV-I. A CTL epitope within the Tax protein was
      identified in this report. HTLV-I-specific CD8+ CTL lines established from two
      HTLV-I carriers with HTLV-I-associated myelopathy or Sjogren syndrome were
      previously demonstrated to kill predominantly the target cells expressing HTLV-I
      Tax. The CTL from two patients showed significant levels of cytotoxicity to
      autologous target cells pulsed with a synthetic peptide of 24 amino acids
      corresponding to the amino-terminal sequences of the Tax protein. Allogeneic
      target cells were also sensitized for CTL by this peptide when the target cells
      have HLA-A2. Tax-specific cytotoxicity, detected as cytolysis of the target cells
      infected with vaccinia virus-HTLV-I recombinant expressing Tax protein, was
      almost completely inhibited by competitor cells pulsed with the synthetic
      peptide. This indicates that a major CTL epitope is present in this peptide.
      Further analysis using shorter peptides revealed that the core sequence of the
      CTL epitope was LLFGYPVYV at positions 11 through 19. This sequence can be
      aligned with the HLA-A2-specific motifs reported recently.

PMID- 1373198
TI  - Cytotoxicity of a replication-defective mutant of herpes simplex virus type 1.
AB  - Replication-defective mutants of herpes simplex virus type 1 (HSV-1) may prove
      useful as vectors for gene transfer, particularly to nondividing cells. Cgal
      delta 3 is an immediate-early gene 3 (IE 3) deletion mutant of HSV-1 that
      expresses the lacZ gene of Escherichia coli from the human cytomegalovirus
      immediate-early control region but does not express viral early or late genes.
      This vector was able to efficiently infect and express lacZ in cells refractory
      to traditional methods of gene transfer. However, 1 to 3 days postinfection, Cgal
      delta 3 induced cytopathic effects (CPE) in many cell types, including neurons.
      In human primary fibroblasts Cgal delta 3 induced chromosomal aberrations and
      host cell DNA fragmentation. Other HSV-1 strains that caused CPE, tested under
      conditions of viral replication-inhibition, included mutants of the early gene
      UL42, the virion host shutoff function, single mutants of IE 1, IE 2, and IE 3,
      and double mutants of IE 3 and 4 and IE 3 and 5. Inhibition of viral gene
      expression by UV irradiation of virus stocks or by preexposure of cells to
      interferon markedly reduced the CPE. We conclude from these studies that HSV-1 IE
      gene expression is sufficient for the induction of CPE, although none of the five
      IE gene products appear to be solely responsible. After infection of human
      fibroblasts with Cgal delta 3 at a low multiplicity of infection, we were able to
      recover up to 6% of the input virus 2 weeks later by a superinfection-rescue
      procedure, even though the virally transduced human cytomegalovirus-lacZ
      transgene was not expressed at this time. It is therefore likely that inhibition
      or inactivation of viral IE gene expression, either for establishing latency or
      for the long-term transduction of foreign genes by HSV-1 vectors, is essential to
      avoid the death of infected cells.

PMID- 1373199
TI  - Ternary complex formation by vaccinia virus RNA polymerase at an early viral
      promoter: analysis by native gel electrophoresis.
AB  - We have resolved, by native gel electrophoresis, two intermediates in the
      transcription of a vaccinia virus early gene by the virus-encoded RNA polymerase.
      Polymerase holoenzyme containing the vaccinia virus early transcription factor
      (VETF) forms a complex of VETF bound to the promoter as the first step in a
      pathway leading to establishment of a committed ternary elongation complex.
      Formation of the VETF-DNA complex is stimulated by magnesium but is uninfluenced
      by nucleoside triphosphates. A stable binary complex of RNA polymerase bound to
      DNA is not detected. Assembly of a gel-stable polymerase-DNA complex depends on
      conditions permissive for RNA synthesis. Nucleotide omission experiments suggest
      that at least a tetrameric RNA must be made before a ternary complex is
      stabilized. RNA analysis indicates that complexes containing nascent transcripts
      20 nucleotides long are stable and active. Ternary complex formation requires
      hydrolyzable ATP. This is consistent with an essential role for the ATPase
      activity of VETF at a step subsequent to DNA binding, as proposed by Broyles (S.
      S. Broyles, J. Biol. Chem. 266:15545-15548, 1991). The ternary complex, once
      formed, is resistant to dissociation by competitor DNA, as well as by salt,
      Sarkosyl, and heparin. The effects of these inhibitory agents on transcription
      complex formation suggest that they target different steps in the assembly
      pathway.

PMID- 1373200
TI  - Identification of T-helper epitopes in the VP1 capsid protein of poliovirus.
AB  - Poliovirus-specific T lymphocytes were isolated from virus-immunized mice of
      different H-2 haplotypes. Immunological characterization of this population
      indicates that the effector population involved in the observed poliovirus
      specific proliferative response was that of CD4-positive T-helper cells.
      Proliferative responses also were induced within these T-lymphocyte populations
      upon stimulation with either purified VP1 capsid protein or VP1 synthetic
      peptides. By using these synthetic peptides, several T-helper epitopes were
      identified. Generally, proliferative responses were observed in three regions of
      VP1. Two regions spanning VP1 residues 86 to 120 and 201 to 241 were recognized
      by T lymphocytes from BALB/c (H-2d), C57BL/6 (H-2b), and C3H/HeJ (H-2k)
      backgrounds. Analyses using synthetic peptides of nonoverlapping sequences
      indicated that the region spanning residues 201 to 241 may contain several T
      epitopes and may account for the strong proliferative response observed. In
      addition, for two of the three haplotypes examined, T epitopes were observed
      within residues 7 to 24 of VP1. Additional epitopes which appeared to be
      restricted to specific H-2 backgrounds were identified. T epitopes within VP1
      that are common between different strains of mice appeared to lie within
      previously identified neutralizing antigenic sites in poliovirus.

PMID- 1373201
TI  - 5-Azacytidine and RNA secondary structure increase the retrovirus mutation rate.
AB  - A broad spectrum of mutations occurs at a high rate during a single round of
      retrovirus replication (V.K. Pathak and H. M. Temin, Proc. Natl. Acad. Sci. USA
      87:6019-6023, 1990). We have now determined that this high rate of spontaneous
      mutation can be further increased by 5-azacytidine (AZC) treatment or by regions
      of potential RNA secondary structure. We found a 13-fold increase in the mutation
      rate after AZC treatment of retrovirus-producing cells and target cells. The AZC
      induced substitutions were located at the same target sites as previously
      identified spontaneous substitutions. The concordance of the AZC-induced and
      spontaneous substitutions indicates the presence of reverse transcription "pause
      sites," where the growing point is error prone. An analysis of nucleotides that
      neighbored substitutions revealed that transversions occur primarily by transient
      template misalignment, whereas transitions occur primarily by misincorporation.
      We also introduced a 34-bp potential stem-loop structure as an in-frame insertion
      within a lacZ alpha gene that was inserted in the long terminal repeat (LTR) U3
      region and determined whether this potential secondary structure increased the
      rate of retrovirus mutations. We found a threefold increase in the retrovirus
      mutation rate. Fifty-seven of 96 mutations were deletions associated with the
      potential stem-loop. We also determined that these deletion mutations occurred
      primarily during minus-strand DNA synthesis by comparing the frequencies of
      mutations in recovered provirus plasmids containing both LTRs and in provirus
      plasmids containing only one LTR.

PMID- 1373202
TI  - The pathogenesis of infection with minute virus of mice depends on expression of
      the small nonstructural protein NS2 and on the genotype of the allotropic
      determinants VP1 and VP2.
AB  - Neonatal C3H/He mice were oronasally inoculated with similar doses of four
      genotypes of minute virus of mice (MVM). MVMp, a fibroblast-specific variant,
      caused an asymptomatic infection. MVM(1035), a chimera which had the allotropic
      determinant of virulent MVMi inserted onto an MVMp background, caused a lethal
      infection and renal papillary infarcts, the hallmark of MVMi infection. MVMi(NS2
      1990), the virulent lymphocyte-specific variant mutated to eliminate NS2
      synthesis, was infectious but caused an asymptomatic infection. Sequential virus
      titration, histology, in situ hybridization with a full-length MVMi genomic
      probe, and immunohistochemistry for viral capsid antigen were used to compare the
      pathogenesis of infection with the four MVM genotypes. Infectious virus was
      recovered from multiple organs of mice infected with MVMi, MVMp, and MVM(1035)
      but not from mice infected with MVMi(NS2-1990). MVMp titers were lower than MVMi
      titers in all organs except the intestine. MVM(1035) titers were higher than MVMi
      titers in all organs except the blood. MVMp was localized to connective tissue
      elements of the intestine, to cells in mesenteric lymph nodes, and rarely to
      cells in other organs. MVM(1035) was localized to multiple organs and shared the
      same target cells, endothelium, lymphoid cells, and hematopoietic cells, as MVMi.
      MVM(1035) also replicated in external germinal cells of the cerebellum and smooth
      muscle cells of the stomach and colon, which were not targets of MVMi or MVMp
      infection. MVMi(NS2-1990) replicated to a limited degree in some MVMi target
      organs.

PMID- 1373203
TI  - Mapping genetic determinants for human immunodeficiency virus type 1 resistance
      to soluble CD4.
AB  - Neutralization of human immunodeficiency virus type 1 (HIV-1) infection with
      soluble CD4 (sCD4) can be achieved over a broad range of concentrations for
      different virus strains. Laboratory virus strains passaged in transformed T-cell
      lines are typically sensitive to sCD4 neutralization, whereas primary virus
      isolates require over 100-fold-higher sCD4 concentrations. Using recombinant
      viruses generated from a laboratory strain, HIV-1NL4-3, and a primary
      macrophagetropic strain, HIV-1JR-FL, we mapped a region of gp120 important for
      determining sensitivity to sCD4 neutralization. This same region has previously
      been defined as important for macrophage and transformed T-cell line tropism and
      includes the V3 neutralization domain but does not include regions of gp120 that
      have been shown to be most important for CD4 binding.

PMID- 1373204
TI  - Mutation of human immunodeficiency virus type 1 at amino acid 585 on gp41 results
      in loss of killing by CD8+ A24-restricted cytotoxic T lymphocytes.
AB  - A human leukocyte antigen A24-restricted CD8+ cytotoxic T-cell clone specific for
      gp41 of human immunodeficiency virus type 1 was isolated from an infected
      individual. The epitope was localized to amino acids 584 to 591 (YLKDQQLL, NL43
      env sequence) of gp41 by using a panel of recombinant vaccinia viruses that
      contain truncated env genes and synthetic peptides. The clone killed autologous B
      lymphoblastoid cell lines pulsed with a synthetic peptide reflecting the sequence
      of the IIIB and MN strains. This clone, however, failed to kill target cells
      pulsed with the peptides that have a mutation from Lys to Arg or Gln at amino
      acid 585 which is present in some prototype human immunodeficiency virus type 1
      strains, e.g., ADA, JFL, SC, ALA1, BAL1, SF2, VRF, SF33, and WMJ2. This finding
      that a mutation at amino acid 585 on gp41 results in nonrecognition by human
      leukocyte antigen A24-restricted CD8+ cytotoxic T lymphocytes suggests that
      antigenic variation at T-cell epitopes contributes to the failure of immune
      control of human immunodeficiency virus type 1 infections.

PMID- 1373205
TI  - Poliovirus chimeras expressing sequences from the principal neutralization domain
      of human immunodeficiency virus type 1.
AB  - Sequences from the principal neutralization domain of human immunodeficiency
      virus type 1 (HIV-1) strain LAI or RF have been expressed in antigenic site 1 of
      the capsid of the Sabin strain of poliovirus type 1. A number of the resulting
      chimeras were viable. Viable variants bearing mutations within the insertion site
      spontaneously arose from several nonviable chimeras. In general, these mutations
      result in a decrease in positive charge in the substituted antigenic site 1. Two
      of the chimeras were genetically stable and have been further characterized. Both
      chimeras were neutralized by various HIV-1 neutralizing antibodies. In rabbits,
      both chimeras produced high levels of antibodies which react with HIV-1 gp120/160
      in immunoprecipitation and enzyme-linked immunosorbent assays. One of the
      chimeras (HIV-1LAI) produced a significant but weak HIV-1 neutralizing response.

PMID- 1373206
TI  - Reverse transcriptase of human immunodeficiency virus type 1: functionality of
      subunits of the heterodimer in DNA synthesis.
AB  - From an in vitro analysis of the DNA-synthesizing abilities of certain
      specifically mutated forms of the heterodimeric reverse transcriptase of human
      immunodeficiency virus type 1, we can conclude that in a heterodimer, the
      functionality of p66 is necessary while the functionality of the p51 subunit is
      not needed. Conversely, p51 is not able to catalyze DNA synthesis when associated
      with p66, and yet when the p66 protein is absent, p51 can function. These
      conclusions applied to DNA synthesis on heteropolymeric RNA and DNA templates.

PMID- 1373208
TI  - [Anesthetic management of a hemophilia A carrier for palliative operation and
      radical repair of a cardiac anomaly].
AB  - We experienced the anesthetic management of a hemophilia A carrier for two
      palliative operations (left and right unifocalization) and radical repair of
      cardiac anomaly. The patient was a ten-year-old girl and her father had
      hemophilia A. She was diagnosed as tetralogy of Fallot, major aortopulmonary
      collateral arteries and pulmonary atresia. Laboratory findings showed prolonged
      bleeding time and activated partial thromboplastin time, and decreased levels of
      factor VIII activity of 26%. When she was eight and nine years old, she underwent
      unifocalization. At both occasions, excessive bleeding tendency continued into
      postoperative period. This time she underwent radical repair in which her
      bleeding tendency was successfully controlled by use of a usual dose of
      concentrated factor VIII for twice.

PMID- 1373207
TI  - A block in release of progeny virus and a high particle-to-infectious unit ratio
      contribute to poor growth of enteric adenovirus types 40 and 41 in cell culture.
AB  - The fastidious enteric adenovirus (FEAd) types 40 (Ad40) and 41 (Ad41) are found
      in stool specimens of infants and young children in association with
      gastroenteritis. Although they can be isolated routinely from clinical specimens
      by using 293 cells, they are propagated with variable success in cell lines which
      support the replication of other adenovirus serotypes. HeLa cells are generally
      considered to be nonpermissive for the replication of FEAds, but in this study,
      Ad40 and Ad41 grew to comparable titers in individual 293 and HeLa cells.
      However, virus was not efficiently released from infected HeLa cells and thus did
      not undergo multiple cycles of infection in HeLa cell cultures. The block in
      virus release was not overcome in KB18 cells which, like 293 cells,
      constitutively express proteins encoded by the E1B region of a subgroup C
      adenovirus (in this case Ad2). Moreover, it was apparent from these studies that
      Ad40 and Ad41 have particle-to-infectious unit ratios several orders of magnitude
      greater than that for Ad5, even in 293 cells which express the E1A and E1B
      proteins of Ad5 and are considered to be permissive for replication of the FEAds.
      Neither the block in release of progeny virus nor the high particle-to-infectious
      unit ratio is explained solely by the defect in expression of the E1B 55K protein
      identified by Mautner et al. (V. Mautner, N. MacKay, and V. Steinthorsdottir,
      Virology 171:619-622, 1989; V. Mautner, N. MacKay, and K. Morris, Virology
      179:129-138, 1990).

PMID- 1373209
TI  - [Effect of ursodeoxycholate on pancreatic exocrine secretion in vitro and in vivo
      study].
AB  - In the present study, we examined the effect of ursodeoxycholate (UDCA) and it's
      taurine conjugate (TUDC) on rat pancreatic exocrine secretion using dispersed
      pancreatic acini (in vitro) and conscious rats (in vivo). In in vitro study 300
      microM UDCA significantly increased 10(-12)-10(-9) M CCK-8 stimulated amylase
      release and change of intracellular Ca2+ concentration, but TUDC did not have
      these effects. In in vivo study intraduodenal infusion of UDCA but not TUDC
      stimulated pancreatic exocrine secretion. Intravenous infusion of secretin
      antibody decreased bicarbonate output, however, this increase was not prevented
      by CCK antagonist. Thus, it was suggested that UDCA has direct action on
      pancreatic acini and UDCA infused intraduodenally stimulates pancreatic
      secretion, possibly via the release of a secretin-like substance. The taurine
      conjugate has weak bioactivity on pancreatic exocrine secretion in both in vitro
      and in vivo.

PMID- 1373210
TI  - On the biochemical modulation of 6-mercaptopurine by methotrexate in murine WEHI
      3b leukemia cells in vitro.
AB  - The chemicals 6-mercaptopurine (6-MP) and methotrexate (MTX) are the cornerstones
      in the maintenance treatment of acute lymphoblastic leukemia. The intracellular
      metabolism of 6-MP to 6-thioguanosine nucleotides (TGN) via 6-thioinosine 5'
      monophosphate (TIMP) is crucial for its cytotoxic effect. MTX inhibits purine de
      novo synthesis and thereby increases the intracellular PRPP being a substrate for
      the phosphoribosylation of 6-MP to TIMP. Hypoxanthine has been shown to inhibit
      the uptake of 6-MP over the cell membrane and the phosphoribosylation of 6-MP to
      TIMP. We have previously shown that the conversion of TIMP to TGN decreases at 6
      MP concentrations above 5 microM in vitro. The aim of the present study was
      therefore to investigate the effect of MTX increasing the PRPP and TIMP
      concentrations and of hypoxanthine decreasing the TIMP concentration on the
      formation of TGN from TIMP. Murine myelomonocytic leukemia cells (WEHI-3b) were
      treated with 6-MP in vitro. The drug concentration was kept constant by
      continuous addition of 6-MP during the experiment. With this technique, the
      concentration of TGN begins to decrease already at 6-MP concentrations above 2
      microM. The addition of 0.2 microM MTX 6 h before 6-MP strongly inhibited the
      purine de novo synthesis, decreased the ATP, and increased the PRPP concentration
      4-fold. The intracellular concentrations of TIMP and to a lesser extent TXMP also
      increased. The concentrations of the TGN were, however, basically unaffected by
      the preincubation with MTX. Simultaneous addition of 20-50 microM hypoxanthine
      and 6-MP decreased the accumulation of all cellular 6-MP metabolites. It is
      concluded that the synergistic cytotoxic effect of the combination of 6-MP and
      MTX is not based on biochemical modulation of the 6-MP metabolism by MTX.

PMID- 1373211
TI  - [Wilson's disease. A histological review of 7 patients and the value of
      histological copper positivity in relation to other hepatopathies].
AB  - BACKGROUND: Wilson's disease is an infrequent entity. Biopsy is essential for
      establishing its presence and degree of hepatopathy but it lacks diagnostic
      specificity. It is necessary to know the significance of positivity or negativity
      of histochemically demonstrated copper when faced with the diagnosis of Wilson's
      disease and cholestatic diseases. METHODS: Nine hepatic sample from 7 patients
      with clinical-biochemical Wilson's disease were reviewed. The rodanine
      histochemical technique was used for demonstration of copper in the samples
      aforementioned and in another 3 kinds of liver diseases: 16 biopsies of primary
      biliary cirrhosis, 86 biopsies of cholestatic hepatopathies (serum bilirubin
      greater than 68 mumol/l) and control biopsies with serum bilirubin less than 42.5
      mumol/l. RESULTS: Among the 7 patients with Wilson's disease, 6 were diagnosed
      with cirrhosis and one chronic active hepatitis. The incidence of erosive
      necrosis (86%), Mallory hyaline (86%), macrovacuolar steatosis (71%),
      glucogenated nuclei (71%) and giant mitochondria (29%) was evaluated. Histologic
      copper deposit with Shikata orcein was objectified in 3 cases (43%) and with
      rodanine in 5 (83%). Positivity with rodanine was 69% among the series of primary
      biliary cirrhosis, 20% among the cholestatic hepatopathies and 0 in the control
      series. CONCLUSIONS: Histology of Wilson's disease remains without definitive
      diagnostic criteria. The disease is diagnosed in a late phase in Spain. The
      sensitivity of the histochemical demonstration of copper with rodanine is high
      (6/7) but its specificity is low, being positive in 68% of primary biliary
      cirrhosis and 19% of other cholestatic hepatopathies.

PMID- 1373213
TI  - Porins and specific channels of bacterial outer membranes.
AB  - Porins and specific channels both produce water-filled pores that allow the
      transmembrane diffusion of small solutes, but the latter contain specific ligand
      binding sites within the channels. Recent structural studies show that many or
      most of these proteins exist as beta-barrels with the beta-strands traversing the
      thickness of the outer membrane. The channels often have diameters in the range
      of 1 nm, and thus the penetration rates of solutes through porin channels are
      likely to be affected strongly by what appear to be minor differences in the
      size, shape, hydrophobicity or charge of the solute molecule. With the specific
      channels, the presence of binding sites can accelerate very significantly the
      diffusion of some ligands when they are present at low concentrations. Thus these
      simple channels can sometimes achieve a surprising degree of real or apparent
      specificity. Recent data tend to favour the idea that these proteins are first
      exported into the periplasm, and then inserted into the outer membrane. Although
      lipopolysaccharides seem to play a significant role in the final assembly of the
      trimeric porins, the details of the targeting process still remain to be
      elucidated.

PMID- 1373212
TI  - Cytophotometric analysis of magnocellular azure B-RNA and Feulgen-DNA following
      chronic GABA infusion into the nucleus basalis of rats.
AB  - This investigation was undertaken to examine possible cytopathic effects of GABA
      infusion on nucleus basalis (NBM) magnocellular neurons. Sixty-three male Long
      Evans rats received unilateral, intra-NBM infusions of either GABA100 (100
      micrograms/microliters/h), GABA10 (10 micrograms/microliters/h), or ultrafiltered
      saline (1 microliter/h) for a period of 24 hours. Rats from each of these groups
      were sacrificed at either 24 hours, 48 hours or 8 days following initiation of
      infusions. The sham operated hemisphere of each rat served as a control for the
      infused hemisphere. After stoichiometric azure B-RNA and Feulgen-DNA staining of
      brain sections, scanning-integrating microdensitometry was used to quantify GABA
      induced alterations in these well established indices of neuronal toxicity. These
      results provide evidence that the neurotoxic effects of 24 hours of 100
      micrograms/microliters-h GABA infusion are manifested within 48 hours post
      initiation of infusions. Although 24 hours of 10 micrograms/microliters-h GABA
      infusion suppressed NBM neuronal metabolism, the lower magnitude and duration of
      this effect signified an impending recovery. GABA infusion resulted in little if
      any NBM neuronal chromatin template impairment (i.e., reduced Feulgen-DNA
      reactivity), irrespective of the dosage employed and the delay prior to
      sacrifice.

PMID- 1373214
TI  - On the distribution of spontaneous SCE in human peripheral blood lymphocytes.

PMID- 1373215
TI  - Chemical purity and mutagenicity: case study of a drug in development.
AB  - During a routine Ames assay of a potential antipsychotic drug candidate, the
      compound appeared to be a frameshift mutagen in Salmonella typhimurium strains
      TA98 and TA1538. Additional testing indicated the mutagenic activity was due to
      one or more contaminants incurred during synthesis. While the compound was
      initially shown to be greater than 98% pure by high-performance liquid
      chromatography, the presence of small amounts (0.01-0.1%) of a highly mutagenic
      impurity produced positive mutagenicity results. The need to assess for chemical
      purity before discontinuing development of drug candidates found positive in the
      Ames assay is discussed.

PMID- 1373216
TI  - Activity of human carcinogens in the Salmonella and rodent bone marrow
      cytogenetic tests.

PMID- 1373217
TI  - On the nature of non-genotoxic carcinogens. A unified theory including NGCs, co
      carcinogens and promoters.

PMID- 1373218
TI  - Mutagenicity of the reaction products of dibenzo-p-dioxin with nitrogen oxides.
AB  - Dibenzo-p-dioxin (DD) was made to react with various concentrations of nitrogen
      oxides in the dark. The mutagenicities of the reaction products were tested using
      Salmonella typhimurium strains TA98, TA100, TA98NR and TA98/1,8-DNP6 in the
      presence or absence of a mammalian metabolic activation system (S9 mix). DD-NOx
      (molar ratios 1:3, 1:6 and 1:18) reaction products exhibited mutagenic potency in
      strains TA98 and TA98/1,8-DNP6 without S9 mix. In a gas chromatography/mass
      spectrometry study, 2-nitrodibenzo-p-dioxin (NDD) was identified with authentic
      sample in the mutagenic reaction products. DD-NOx (1:18) reaction products were
      reduced by sodium hydrogen sulfide and the reduction mixture was analyzed by
      HPLC. 2,7-Dinitrodibenzo-p-dioxin (DNDD) and 2,8-DNDD were identified as
      corresponding diamino-DDs in the reduction mixture. 2-NDD, 2,7-DNDD and 2,8-DNDD
      were also mutagenic in strains TA98 and TA98/1,8-DNP6 without S9 mix and the
      mutagenicity of DD-NOx reaction products was largely accounted for by the nitro
      DDs.

PMID- 1373219
TI  - Genotoxic activity of methyl mercury chloride and dimethyl mercury in human
      lymphocytes.
AB  - The genotoxicity of methyl mercury chloride (MMC, 0-25 x 10(-6) M) and dimethyl
      mercury (DMM, 0-434 x 10(-6) M) was evaluated by chromosome metaphase analysis in
      human lymphocytes treated in vitro for 24 h. Structural (CA) and numerical (AN)
      chromosomal aberrations were scored for the assessment of induced genotoxic
      effects, while the variation in mitotic index (MI) was considered a monitor for
      induced cellular toxicity. MMC induced CA and AN in a dose-related manner at
      doses exceeding 0.6 x 10(-6) M, and the proportion of cells with CA was
      constantly and significantly higher than that of cells with AN. DMM was able to
      induce both effects as well, although to a lesser extent than MMC, CA and AN
      being induced at doses exceeding 43.4 x 10(-6) M and 1.73 x 10(-6) M,
      respectively. MMC was 6-fold more effective in inducing CA than DMM at equivalent
      toxic doses. On the other hand, no significant difference was observed between
      the two compounds in inducing AN. Therefore MMC was much more clastogenic than
      DMM, whereas mitotic spindle disturbances appeared to be almost equally induced
      by both compounds.

PMID- 1373220
TI  - Published data on mutagenesis by ionizing radiation of plasmids in solution
      probably reflect in part the specificity of adventitious transition metal ions
      complexed to the DNA.
AB  - A number of recent papers show that single base changes induced by mutagenesis
      with ionizing radiation of genes on plasmids in solution, followed by
      transfection into mammalian or bacterial cells for assay, are mostly at G:C base
      pairs, with mutagenic hot spots. Genes irradiated in mammalian or bacterial
      cells, on the other hand, have comparable numbers of base changes at all sites,
      with no evidence for hot spots. The differences are ascribed to induction of many
      base change mutations in vitro by reactions catalyzed by adventitious transition
      metal ions complexed to the DNA. Reasons are given why this process should play a
      much smaller role in vivo.

PMID- 1373221
TI  - Antagonists to cholinergic receptors increase the frequency of binuclear V79
      Chinese hamster cells. A mechanism for induction of aneuploidy.
AB  - V79 Chinese hamster cells were found to produce significant amounts of
      acetylcholine. Asynchronously growing V79 cells were treated with five different
      antagonists to cholinergic receptors: atropine and scopolamine, which are
      inhibitors of muscarinic receptors, and mecamylamine, d-tubocurarine and alpha
      bungarotoxin, which are inhibitors of nicotinic receptors. All compounds caused a
      slight but significant increase of the frequency of binuclear interphase cells
      and also of the frequency of cells in late telophase and early G1 that had not
      completed cleavage. In addition, hemicholinium-3, a specific choline uptake
      antagonist, inhibited cleavage. Taken together, it seems reasonable to
      hypothesize that acetylcholine and its receptors take part in the regulation of
      cleavage in these cells. As binuclear cells are prone to aberrant spindle
      functions in following mitoses, inhibition of cleavage may constitute a risk for
      generation of cells with highly aberrant chromosome numbers.

PMID- 1373222
TI  - Effects of benzyladenine on prokaryotic and eukaryotic cells.
AB  - Comparative studies of the effect of benzyladenine (BA) on the yeast
      Saccharomyces cerevisiae, the bacterium Salmonella typhimurium, the shallot
      Allium ascalonicum and Chinese hamster fibroblast cells were performed. The
      tested substance had no mutagenic activity on yeast, bacteria and cultured
      fibroblast cells. Changes in mitotic activity and cell division abnormalities
      were observed after BA treatment in shallot root-tip cells.

PMID- 1373223
TI  - The effect of tequila in the synaptonemal complex structure of mouse
      spermatocytes.
AB  - The effect of tequila in the synaptonemal complex (SC) of mouse spermatocytes was
      determined. We tested 3 dosages (2.1, 4.2 and 8.4 g/kg) administered in a single
      intraperitoneal inoculation. The frequency of SC alterations was established in
      pachytenic nuclei 5 days after the administration using a silver impregnation
      technique. Three types of alterations were observed (desynapses, breaks and
      multiaxials) and the rate of each alteration was compared with that obtained with
      appropriate controls, including cyclophosphamide (CP) (150 mg/kg). The results
      showed a significant increase induced by tequila only in the frequency of
      desynapses. This damage began at the second highest dose (4.2 g/kg). The other SC
      alterations were in the control range. CP, however, induced a significant
      increase in all 3 types of SC alterations.

PMID- 1373224
TI  - Kinetochore-staining of spermatid micronuclei: studies of mice treated with X
      radiation or acrylamide.
AB  - The rodent spermatid micronucleus (MN) assay was used in conjunction with
      immunofluorescent techniques to distinguish kinetochores in MN following exposure
      of mice to X-radiation or acrylamide. After either treatment, modest increases in
      kinetochore-positive MN were observed. Spermatids which had been exposed during
      meiotic prophase to X-rays (400 cGy) had approximately 10-fold increases in MN
      compared to controls; up to 15% of the MN observed were kinetochore-positive.
      Following acrylamide treatment of meiotic prophase cells, there was a doubling of
      spermatid MN over baseline levels, approximately one-third of which were
      kinetochore-positive.

PMID- 1373225
TI  - Cytogenetic effects of cyanazine and metolachlor on human lymphocytes exposed in
      vitro.

PMID- 1373226
TI  - Myelodysplasia and leukemia after treatment of aplastic anemia with G-CSF.

PMID- 1373227
TI  - Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of
      modulation.
AB  - The roles of N-methyl-D-aspartate (NMDA) receptors and protein kinase C (PKC) are
      critical in generating and maintaining a variety of sustained neuronal responses.
      In the nociceptive (pain-sensing) system, tissue injury or repetitive stimulation
      of small-diameter afferent fibres triggers a dramatic increase in discharge (wind
      up) or prolonged depolarization of spinal cord neurons. This central
      sensitization can neither be induced nor maintained when NMDA receptor channels
      are blocked. In the trigeminal subnucleus caudalis (a centre for processing
      nociceptive information from the orofacial areas), a mu-opioid receptor agonist
      causes a sustained increase in NMDA-activated currents by activating
      intracellular PKC. There is also evidence that PKC enhances NMDA-receptor
      mediated glutamate responses and regulates long-term potentiation of synaptic
      transmission. Despite the importance of NMDA-receptors and PKC, the mechanism by
      which PKC alters the NMDA response has remained unclear. Here we examine the
      actions of intracellularly applied PKC on NMDA-activated currents in isolated
      trigeminal neurons. We find that PKC potentiates the NMDA response by increasing
      the probability of channel openings and by reducing the voltage-dependent Mg2+
      block of NMDA-receptor channels.

PMID- 1373228
TI  - Normal development and behaviour of mice lacking the neuronal cell-surface PrP
      protein.
AB  - PrPC is a host protein anchored to the outer surface of neurons and to a lesser
      extent of lymphocytes and other cells. The transmissible agent (prion)
      responsible for scrapie is believed to be a modified form of PrPC. Mice
      homozygous for disrupted PrP genes have been generated. Surprisingly, they
      develop and behave normally for at least seven months, and no immunological
      defects are apparent. It is now feasible to determine whether mice devoid of PrPC
      can propagate prions and are susceptible to scrapie pathogenesis.

PMID- 1373229
TI  - [Cytokines as immunotherapy in cancer].

PMID- 1373230
TI  - The prevalence of antibody to hepatitis C virus in a dialysis population.

PMID- 1373231
TI  - [Somatostatin in the prevention of postoperative increase of pancreatic enzyme
      after pancreatic surgery].
AB  - The prophylactic effect of perioperative use of somatostatin on postoperative
      increase of pancreatic digestive enzymes was investigated in this double blind,
      randomized study. Thirty three patients undergoing pancreatic surgery because of
      chronic pancreatitis were divided randomly into two groups. Fifteen patients
      received somatostatin- (dose 125 micrograms/hour), 18 placebo-infusion, pre- and
      postoperatively for a total time of 48 hours. The level of serum amylase, lipase,
      gammaGT, calcium, creatinine and blood glucose was determined every 12 hours. In
      the placebo group the serum lipase and amylase increased significantly (p less
      than 0.001), while the calcium decreased. In the somatostatin treated patients
      only the lipase level increased significantly (p less than 0.01), while the
      amylase and calcium showed no significant changes compared to their initial
      values. The postoperative increase in serum enzyme levels is interpreted as being
      an indicator of pancreatic injury. These results suggest that the perioperative
      use of somatostatin has beneficial effect for the prevention of pancreatic
      enzymes increases, associated with pancreatic surgery or its complications in
      patients with chronic pancreatitis.

PMID- 1373232
TI  - Decreased granulocyte-macrophage colony-stimulating factor production by human
      neonatal blood mononuclear cells and T cells.
AB  - Impaired production and delivery of neutrophils to the site of infection have
      been implicated in the increased susceptibility of the neonate to infection.
      Because granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte
      colony-stimulating factor (G-CSF) play critical roles in the production of
      neutrophils from marrow precursors, we assessed the ability of leukocytes from
      neonates and adults to produce GM-CSF, G-CSF, and, for comparison, macrophage
      colony-stimulating factor (M-CSF) after stimulation with concanavalin A +/-
      phorbol myristate acetate [blood mononuclear cells (MC) and T lymphocytes] or
      lipopolysaccharide (monocytes). MC and monocytes from adult and neonatal subjects
      produced mRNA for GM-CSF, G-CSF, and M-CSF, whereas T cells produced only GM-CSF
      mRNA. Neonatal MC and T cells accumulated only approximately 30% as much GM-CSF
      mRNA as did adult MC and T cells. In contrast, the accumulation of GM-CSF mRNA by
      neonatal and adult monocytes was similar. Neonatal MC also accumulated similar
      amounts of G-CSF mRNA and somewhat more M-CSF mRNA than did adult MC; results
      with monocytes were similar to those with MC. Results of colony-stimulating
      activity bioassays on supernatants from neonatal and adult MC stimulated with
      concanavalin A paralleled the mRNA results.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373233
TI  - Hepatic protein synthesis in suckling rats: effects of stage of development and
      fasting.
AB  - We studied the developmental changes in hepatic protein synthesis in suckling
      rats between postpartum d 1 and 28 and investigated the effect of fasting for 10
      or 18 h on hepatic protein turnover at postpartum d 5, 10, 16, and 28. Fractional
      protein synthesis rates (KS, %/d) were measured in vivo using a flooding dose of
      L-[4-3H]phenylalanine. Although hepatic KS and translation efficiency (protein
      synthesis/unit RNA) were significantly higher at postpartum d 28 than d 1, the
      pattern of change was biphasic: KS and translational efficiency were higher at d
      10 and 28 than at d 5 and 16. The largest increase in KS and translational
      efficiency occurred during the period normally associated with weaning (between
      postpartum d 16 and 28). At all stages of development, the KS and translational
      efficiency in fasted rats were significantly lower than those in control (fed)
      rats, although the relative decline in both measurements was largest at
      postpartum d 10. The absolute rates of hepatic protein synthesis declined to
      similar levels on d 5, 10, and 16 after 10 h of fasting and changed little after
      18 h of fasting; this level was significantly higher at postpartum d 28. Our
      results suggest that postnatal development in suckling rats was marked by a
      biphasic pattern in the rates of hepatic protein synthesis, which increased
      during the neonatal and weaning periods. The relative changes in the synthesis
      and loss of hepatic protein in response to fasting were greater during the
      neonatal than during the late suckling and weaning periods.

PMID- 1373234
TI  - Synthesis and base-pairing properties of the nuclease-resistant alpha-anomeric
      dodecaribonucleotide alpha-[r(UCUUAACCCACA)].
AB  - The non natural oligoribonucleotide alpha-[r(UCUUAACCCACA)] consisting
      exclusively of alpha-anomeric ribonucleoside units was synthesized according to
      the phosphoramidite methodology and the solid support technology. For this
      purpose, the base-protected alpha-ribonucleosides were synthesized and converted
      into their O-methylphosphoramidites. Assembling was carried out on a DNA
      synthesizer with an average efficiency of 97% per step. Base composition of this
      nuclease-resistant alpha-RNA strand was ascertained after chemical and enzymatic
      hydrolysis and HPLC analysis of the hydrolysate. Whereas no spectroscopic
      evidence of base pairing was found above 0 degrees C between alpha
      [r(UCUUAACCCACA)] and beta-[d(TGTGGGTTAAGA)], a clear UV absorbance transition
      (Tm 25.5 degrees C) was observed during the hybridization of the same alpha-RNA
      strand with beta-[d(AGAATTGGGTGT)]. In this latter case, the mixing curve
      titration suggests formation at low temperature of a triplex involving two alpha
      RNA and one beta-DNA strands. Moreover, this alpha-decaribonucleotide
      complementary in parallel orientation of the splice receptor of HIV-1 tat mRNA
      was found to inhibit (10 microM less than ED50 less than 20 microM), with
      apparent lack of sequence specificity, the de novo HIV-1 infection in cultured
      cells.

PMID- 1373235
TI  - Mutations which alter splicing in the human hypoxanthine-guanine
      phosphoribosyltransferase gene.
AB  - A large proportion of mutations at the human hprt locus result in aberrant
      splicing of the hprt mRNA. We have been able to relate the mutation to the
      splicing abnormality in 30 of these mutants. Mutations at the splice acceptor
      sites of introns 4, 6 and 7 result in splicing out of the whole of the downstream
      exons, whereas in introns 1, 7 or 8 a cryptic site in the downstream exon can be
      used. Mutations in the donor site of introns 1 and 5 result in the utilisation of
      cryptic sites further downstream, whereas in the other introns, the upstream
      exons are spliced out. Our most unexpected findings were mutations in the middle
      of exons 3 and 8 which resulted in splicing out of these exons in part of the
      mRNA populations. Our results have enabled us to assess current models of mRNA
      splicing. They emphasize the importance of the polypyrimidine tract in splice
      acceptor sites, they support the role of the exon as the unit of assembly for
      splicing, and they are consistent with a model proposing a stem-loop structure
      for exon 8 in the hprt mRNA.

PMID- 1373236
TI  - Chemical synthesis of RNA using fast oligonucleotide deprotection chemistry.
AB  - The exocyclic amine protecting groups in oligonucleotide synthesis which require
      8-16 hours at 55 degrees C for deprotection in ammonia have been replaced with
      more labile base protecting groups (dimethylformamidine for adenine and guanine
      and isobutyryl for cytosine). Using these fast oligonucleotide deprotecting
      groups which require 2-3 hours at 55 degrees C for complete deprotection, a new
      set of cyanoethyl phosphoramidite ribonucleoside monomers and supports has been
      developed. Ribozymes and substrate RNAs which were synthesized with these
      phosphoramidites were assayed and were found to have full catalytic (biological)
      activity.

PMID- 1373237
TI  - A pyrimidine-guanine sequence-specific ribonuclease from Rana catesbeiana
      (bullfrog) oocytes.
AB  - A pyrimidine-guanine sequence-specific ribonuclease (RC-RNase) was purified from
      Rana catesbeiana (bullfrog) oocytes by sequential phosphocellulose, Sephadex G75,
      heparin Sepharose CL 6B and CM-Sepharose CL 6B column chromatography. The
      purified enzyme with molecular weight of 13,000 daltons gave a single band on SDS
      polyacrylamide gel. One CNBr-cleaved fragment has a sequence of
      NVLSTTRFQLNT/TRTSITPR, which is identical to residues 59-79 of a sialic acid
      binding lectin from R. catesbeiana eggs, and is 71% homologous to residues 60-80
      of an RNase from R. catesbeaina liver. The RC-RNase preferentially cleaved RNA at
      pyrimidine residues with a 3' flanking guanine under various conditions. The
      sequence specificity of RC-RNase was further confirmed with dinucleotide as
      substrates, which were analyzed by thin layer chromatography after enzyme
      digestion. The values of kcat/km for pCpG, pUpG and pUpU were 2.66 x 10(7) M-1s
      1, 2.50 x 10(7) M-1s-1 and 2.44 x 10(6) M-1s-1 respectively, however, those for
      other phosphorylated dinucleotides were less than 2% of pCpG and pUpG. As
      compared to single strand RNA, double strand RNA was relatively resistant to RC
      RNase. Besides poly (A) and poly (G), most of synthetic homo- and
      heteropolynucleotides were also susceptible to RC-RNase. The RC-RNase was stable
      in the acidic (pH 2) and alkaline (pH 12) condition, but could be inactivated by
      heating to 80 degrees C for 15 min. No divalent cation was required for its
      activity. Furthermore, the enzyme activity could be enhanced by 2 M urea, and
      inhibited to 50% by 0.12 M NaCl or 0.02% SDS.

PMID- 1373239
TI  - The North American Society of Pacing and Electrophysiology (NASPE), 13th annual
      scientific session. May 14-16, 1992, Chicago, Illinois. Abstracts.

PMID- 1373238
TI  - Three RFLPs for pZ11 (DXS540) in the choroideremia gene at Xq21.2.

PMID- 1373240
TI  - Rhabdomyosarcoma in a congenital pigmented nevus.
AB  - A 7-month-old boy had a giant pigmented lesion involving the trunk and thighs
      that exhibited many hyperpigmented hairy and verrucous nevi. One of the nevi
      ulcerated and on histological examination consisted of pleomorphic
      rhabdomyosarcoma cells that stained for muscle-specific actin (HHF-35), desmin,
      and myoglobin. Around the tumor, in the dermis, benign pigmented nevus cells were
      observed. The occurrence of malignant tumors, other than malignant melanoma, in
      pigmented nevi is rarely described.

PMID- 1373241
TI  - Photodynamic inactivation of an ion channel: gramicidin A.
AB  - The ion channel formed by the peptide gramicidin A in planar lipid membranes is
      inactivated by visible light in the presence of the photosensitizer Rose Bengal.
      This is concluded from the strong decrease of the membrane conductance by more
      than two orders of magnitude. Experiments performed at different oxygen
      concentrations, in the presence of the singlet oxygen quenchers beta-carotene or
      alpha-tocopherol indicate, that presumably a type I process between the dye Rose
      Bengal and the tryptophan residues of the gramicidin channel with a subsequent
      oxidation of the tryptophans is responsible for the loss of the conductance
      properties of the channel.

PMID- 1373242
TI  - Malignant microvasculature in abdominal tumors in children: detection with
      Doppler US.
AB  - Malignant tumors produce a network of microscopic, thin-walled vessels that
      invade the host and provide the blood supply essential for growth. This network,
      situated at the periphery of malignant tumors, gives rise to characteristic, high
      velocity Doppler shifts at ultrasound (US) scanning and was sought in 54 children
      with abdominal masses. Characteristic high-frequency Doppler signals (greater
      than 2.5 kHz) were found in 27 of 35 malignant tumors. These signals disappeared
      during successful chemotherapy in three children with neuroblastoma in whom the
      signals had been documented initially. The signals were absent in three other
      children, who had undergone clinically successful therapy, and were present in
      two children with rapidly progressing tumors despite chemotherapy. In 14
      children, none of the benign tumors showed high-frequency Doppler shifts. The
      search for malignant neovasculature with Doppler US scanning may provide insight
      into tumor behavior. The Doppler US examination, a noninvasive adjunct to routine
      US, may become useful at both the time of diagnosis of a mass and afterward to
      assess the effect of chemotherapy.

PMID- 1373243
TI  - [Transposition of the great arteries. A follow-up of patients operated on with
      atrial correction].
AB  - The late results of 146 patients with transposition of the great arteries
      (simple: 119, complex: 27) surviving to physiological correction (Mustard: 33,
      Senning: 113) are analyzed. The mean age at operation was 27 months (1-120), and
      the mean follow-up was 78 months (6-187). The mean P wave voltage significantly
      decreased (from 0.3 mV preoperatively to 0.16 mV postoperatively). Frontal mean P
      wave axis varied from 63.9 degrees to 71.3 degrees. Mean heart rate were
      significantly lower than those for age-matched normal children. Previous
      atrioseptectomy had been performed in 36 patients and five of them had
      arrhythmias before operation. 78 (55%) out of the remaining 141 showed
      arrhythmias in the surface ECG: sinus node disfunction in 51, tachyarrhythmias in
      eight, atrioventricular block in eight and several association of arrhythmias in
      11. Actuarial survival free of arrhythmias is 81% at the first year, 49% at 5
      years and 22% at 15 years. The incidence of arrhythmias in the group of 92
      patients with Holter monitoring was higher, with 73 cases having arrhythmias
      (79%): sinus node disfunction in 47, tachyarrhythmias in ten, atrioventricular
      block in four and associated in 12. Survival free of arrhythmias by both methods
      (ECG and Holter) shows a 78% at the first year, 28% at 5 years and 5.6% at 15
      years. No significant correlation was found between the incidence of arrhythmias
      and the type of TGA (simple or complex) or the surgical technique (Mustard or
      Senning). Permanent pacemakers were implanted in seven to a mean follow-up of 7
      years. Five patients were reoperated to a mean follow-up of 46 months. There were
      7 late deaths to a mean follow-up of 13 months, four of them being sudden. The
      actuarial survival rate for the whole group was 93.5% at 15 years. No significant
      correlation was found between the late mortality and the type of TGA or
      operation. There was also no correlation with the incidence of arrhythmias.
      Residual lesions were found in 46 patients, hemodynamically significant in ten.
      Functional status was class I (NYHA) in 123, and class II in 16. There was
      correlation between the functional class and the residual lesions.

PMID- 1373244
TI  - [The expansion of NK CD56+ cells with reduced cytotoxicity in a female patient
      with systemic sclerosis].
AB  - An absolute and relative increase of circulating CD56+ (NKH1, Leu19) natural
      killer cells has been found in a patient with systemic sclerosis. The expanded
      natural killer cells exhibited reduced natural killer activity and antibody
      dependent cell-mediated cytotoxicity. Furthermore, the limiting dilution analysis
      of spontaneous in vitro immunoglobulin synthesis demonstrated that the precursor
      frequency of immunoglobulin-secreting cells and the "single-hit" kinetics of the
      titration curve were similar to healthy controls, but strongly different from
      previously reported patients in whom CD16+NK cell subset was expanded. Thus, our
      findings might suggest that expanded CD56+ natural killer cells exhibit unique
      regulatory properties on B cell function in systemic sclerosis.

PMID- 1373246
TI  - Acute cytotoxic effect of cyclosporin A on pancreatic acinar cells in rats.
      Protective effect of the synthetic protease inhibitor E3123.
AB  - This study was designed to evaluate the acute toxic effects of cyclosporin A on
      the exocrine pancreas and the protective effects of a new potent protease
      inhibitor, 4-(2-succinimidoethylthio) phenyl 4-guanidinobenzoate
      methanesulfonate, E3123. Cyclosporin A in a dose of 5 mg/kg.h caused a
      significant increase in serum amylase levels, pancreatic amylase content, and
      interstitial edema, suggesting that it induces exocrine pancreatic injury.
      Cyclosporin A also caused redistribution of cathepsin B from the lysosomal
      fraction to the zymogen fraction, indicating colocalization of lysosomal enzymes
      with pancreatic digestive enzymes. E3123 in a dose of 2 mg/kg.h prevented almost
      completely these changes caused by cyclosporin A. These results indicate that
      exocrine pancreatic injury is induced by cyclosporin A and that lysosomal enzymes
      play important roles in the pathogenesis of this injury and also suggest that
      E3123 might protect the exocrine pancreas of patients receiving cyclosporin A
      after organ transplantation.

PMID- 1373247
TI  - [Approaches to neuropsychiatry as a transition in the separation of neurology and
      psychiatry].
AB  - The focus of the article is on the separation of neurology and psychiatry and
      their interconnection by means of the discipline of neuropsychiatry. First, the
      oppositions of "Structure versus Functions" and "Localization versus Holism" are
      worked out as the main reasons for the separation of neurology and psychiatry.
      This is followed by the demonstration of the recent developments of "biological
      psychiatry", "behavioral neurology" and "neuropsychology" which try to bridge the
      gulf between neurology and psychiatry. Their inadequacies with regard to a real
      bridge between the two disciplines, which takes account for both sides, is shown.
      Consecutively, a specific neuropsychiatric conception as a functional dynamic
      one, is suggested, which can be distinguished from the approaches in "biological
      psychiatry" and "behavioral neurology". This neuropsychiatric conception is
      applied, in a last step, to the oppositions of "Structure versus Function" and
      "Localization versus Holism", by means of which these oppositions, and the one
      between neurology and psychiatry, can be bridged--this is exemplified by means of
      the Parkinson-Syndrome with its neurologic and psychiatric symptoms.

PMID- 1373248
TI  - [Electrodermal hypoactivity in depression: psychobiological marker or
      differential psychophysiologic disposition?].
AB  - Research about the dominating hypoactivity in electrodermal system in affective
      disorders led to the assumption that electrodermal activity (EDA) could be an
      important biopsychological trait in the etiology of depression. However,
      experimental results are contradictory. Some studies find nosological validity,
      other studies an influence of psychomotor status on EDA or correlations to
      clinical improvement, etc. Most of these results are based on laboratory
      conditions (habituation experiment with tones). The person-situation-environment
      interaction and their dynamic process regulation on electrodermal activity are
      neglected. Also lacking is a comparable description of nosology, psychomotor
      status and experimental design. After discussing the neuropsychological
      background of the habituation paradigm which led to the "traditional" assumptions
      of the correlation between electrodermal activity and depression, results of
      different samples are shown tested over years using always the same
      classification and experimental methods. None of our assumptions could be
      verified. Although low levels in SCL dominate, we could not find results of high
      sensitivity and specificity in contrast to controls. However we found differences
      in other, more complex experiments containing personality traits and reactions to
      emotional words. In a multi-level process-oriented stress paradigm of the
      success/failure type we found a delay in regeneration of psychological and
      electrodermal measures after failure. This results demonstrate that investigation
      in electrodermal activity needs more complex and process-oriented experimental
      designs. EDA probably has not the quality of a biological marker, but seen in the
      context of person and situation factors it differentiates depressed states.

PMID- 1373245
TI  - The roles of ionic processes in muscular fatigue during intense exercise.
AB  - Muscular fatigue is manifested by a decline in force- or power-generating
      capacity and may be prominent in both submaximal and maximal contractions.
      Disturbances in muscle electrolytes play an important role in the development of
      muscular fatigue. Intense muscular contraction is accompanied by an increased
      muscle water content, distributed in both intracellular and extracellular spaces.
      This water influx will modify ionic changes in both compartments. Changes in
      muscle intracellular electrolyte concentrations with intense contraction may be
      summarised as including decreases in potassium (6 to 20%) and in creatine
      phosphate (up to 70 to 100%) and increases in lactate (more than 10-fold), sodium
      (2-fold) and small, variable increases in chloride. The net result of these
      intracellular ionic concentration changes with exercise will be a reduction in
      the intracellular strong ion difference, with a consequent marked rise in
      intracellular hydrogen ion concentration. This intracellular acidosis has been
      linked with fatigue via impairment of regulatory and contractile protein
      function, calcium regulation and metabolism. Potassium efflux from the
      contracting muscle cell dramatically decreases the intracellular to extracellular
      potassium ratio, leading to depolarisation of sarcolemmal and t-tubular
      membranes. Surprisingly little research has investigated the effects of intense
      exercise training on electrolyte regulation and fatigue.

PMID- 1373249
TI  - [Continuity and discontinuity of psychopathology: a study of patients examined as
      children and as adults. I. Antecedents of adult schizophrenic disorders].
AB  - The demographical stability of the Canton of Geneva made it possible for us to do
      a prospective study of all the children who had consulted the Child Psychiatry
      Service between 1963 and 1967 and who later consulted the public adult psychiatry
      services. On the basis of the adult diagnoses, wo looked for specific clinical
      "clusters" in childhood which would allow us to differentiate statistically the
      groups of children. We present here the results of the group of children who
      developed schizophrenia in adulthood. We found a specific childhood "cluster"
      which clearly distinguishes these children from the others. It includes: serious
      relational disorders, neurodevelopmental impairment, attention deficit and school
      learning disorders.

PMID- 1373250
TI  - [Dimensions of depressive behavior].
AB  - This study investigates the significance of a schedule of modes of behavior by
      comparing depressive and non-depressive persons. Using factor analytical methods
      it can be shown that behavioral modes of depressives form a heterogeneous group.
      Furthermore, it seems that two diametrically opposed mechanisms underlie
      depressive behavior: increase or decrease of behavioral mode frequency.

PMID- 1373251
TI  - Methylbromide intoxication: a case report.
AB  - This work focuses on the neurophysiological features in a patient with action
      myoclonus and mental deterioration following methylbromide intoxication. The
      patient is a 28-year-old man, without respiratory distress or exposure to other
      toxics. Myoclonus improved with polytherapy (clonazepam, 5-HT, carbidopa, GABA).
      The neurophysiological and neuropsychological evidence in this patient suggests a
      possible double site of action of methylbromide at cortical and subcortical
      levels.

PMID- 1373252
TI  - [Polyneuropathy in hyperthyroidism--a clinical neurophysiologic study].
AB  - In this prospective study, 27 patients with hyperthyroidism were evaluated
      neurophysiologically. There were 24 women and 3 men: the mean age was 56.4 years
      (range 21 to 84 years). Neurologic complaints of the patients were muscle
      weakness (59.3%), muscle cramps (18.5%) and sensory symptoms (11.1%). Tendon
      reflexes were increased in 18.5% and decreased in 14.8%, respectively. While the
      motor nerve conduction velocities (NCV) of the tibial and the peroneal nerve
      revealed normal results in the majority of patients, there were pathological
      findings of the sensory NCV of the sural nerve in 29.6% of patients. In another
      22.2%, borderline findings were obtained. Six patients presented myopathic
      changings in electromyography of the m.vastus lateralis. Neither neuropathic nor
      myopathic findings correlated with the serum levels of TT3, TT4 or the T4/TBG
      quotient. A polyneuropathy in hyperthyroidism seems not to be uncommon and is
      probably caused by hypermetabolism in thyroid hyperfunction.

PMID- 1373253
TI  - Prevalence of anti-hepatitis C virus antibodies in positive FTA-ABS non-drug
      abusing female prostitutes in Spain.
AB  - The prevalence of antibodies against Hepatitis C Virus (anti-HCV antibodies) and
      its association with the presence of treponemal antibodies (FTA-ABS) was studied
      in 227 non-drug abusing female prostitutes. The overall anti-HCV antibody
      prevalence was 8.8%, and a significantly higher prevalence of anti-HCV antibodies
      was found in prostitutes testing positive for FTA-ABS (19.4%) than in prostitutes
      testing negative for FTA-ABS (3.9%) (PR = 5.023, P less than 0.001). No
      statistical association was found between patient age or the duration of
      prostitution and the presence of anti-HCV antibodies.

PMID- 1373254
TI  - T2- and diffusion-weighted magnetic resonance imaging of a focal ischemic lesion
      in rat brain.
AB  - BACKGROUND AND PURPOSE: We sought to evaluate the application of T2-weighted and
      diffusion-weighted magnetic resonance imaging techniques in the study of a focal
      ischemic lesion in the rat brain. METHODS: Unilateral cortical infarcts were
      induced using the photosensitive dye rose bengal and 560 nm light irradiation.
      Magnetic resonance images were recorded from a total of 11 rats at selected
      intervals from 1.5 hours to several days after induction of the lesion. Parallel
      experiments were performed in which Evans blue dye was injected into the lesioned
      animals either immediately after lesion induction (n = 11) or 1 hour before the
      animals were killed (n = 11). The second procedure was designed to show regions
      of blood-brain barrier permeability to plasma proteins at the time of sacrifice,
      whereas the first procedure showed the accumulation and subsequent dispersion of
      plasma protein following disruption of the blood-brain barrier. RESULTS: Regions
      of the cortex highlighted by the T2-weighted images corresponded well to the
      pattern of dye staining seen from the first procedure while the diffusion
      weighted images showed visual correspondence with the staining pattern obtained
      using the second procedure. CONCLUSIONS: These results illustrate the
      complementary use of T2-weighted and diffusion-weighted magnetic resonance
      imaging in discerning the pathophysiology of developing lesions.

PMID- 1373255
TI  - [Clodronate in the palliative therapy of bone-metastasized prostatic carcinoma].
AB  - Activity and side-effects of clodronate (Ostac), an inhibitor of osteoclastic
      bone resorption, were recorded in an open prospective uncontrolled study on 35
      patients with metastatic prostatic cancer. All patients had progressive
      symptomatic bone metastases despite prior hormone therapy. Clodronate was
      initially administered i.v. for 8 days with 300 mg/day. This was followed by a
      daily oral administration of 1600 mg. The analgesic effect was evaluated by using
      a visual analogue scale and by recording the daily consumption of analgesic
      drugs. Karnofsky index and routine blood examinations, including PSA, were
      assessed. Repeated bone scans and radiological evaluations were performed. An
      improvement in pain was observed in 71% of the patients. The mean duration of
      improvement was 4 weeks. Average survival time was 12 weeks. There were no side
      effects after i.v. administration. Slight gastrointestinal discomfort was
      observed in 3 patients after oral administration. No effect was observed on the
      extent or biology of the metastases. Clodronate is an effective drug for
      palliative treatment of symptomatic bone metastases of prostatic carcinoma. It
      causes fewer and less pronounced side effects than other palliative drug
      therapies.

PMID- 1373256
TI  - Specificity of affinity-purified Trichinella spiralis antigens.
AB  - An affinity-purified fraction (APF) was obtained by passing crude somatic
      antigens of Trichinella spiralis muscle larvae through an Affi-Gel 10 column
      coupled with anti-Trichuris suis IgG. The fraction contained seven antigens with
      molecular weights ranging from 28 to 55 kDa. When tested with antiserum against
      other common nematodes of pigs from China, the APF was found to be markedly more
      specific than S3 antigens (prepared by a combination of cell fractionation and
      differential centrifugation according to Despommier and Lacetti, 1981) and
      fractions produced by Sephacryl S-200 gel filtration (F1 to F12). When the APF
      was used in an indirect IgG-enzyme-linked immunosorbent assay (IgG-ELISA) to
      screen serum samples from 2000 pigs imported from China, a positive rate of 7.5%
      was obtained. Similar screenings using the crude somatic antigens F1 and S3 gave
      a large number of cross-reactions and false positive reactions. Positive rates of
      48%, 39% and 59.5% respectively were obtained for the three antigens.

PMID- 1373257
TI  - Desmoplastic melanoma: patterns of recurrence.
AB  - Desmoplastic melanoma is a rare type of malignant melanoma, recognized since
      1971. Other variants of desmoplastic melanoma include neural transforming
      melanoma and neurotropic melanoma. The pathology and clinical features of 58
      patients whose tumor had the features of desmoplastic melanoma, neural
      transforming melanoma, and neurotropic melanoma, either separately or in
      combination, were examined to assess patterns of recurrent disease. The tumor was
      situated on the head and neck in 41% of patients and was amelanotic in 71% of
      patients. There was an associated superficial melanoma in 48% of patients. There
      was a combination of the 3 histologic patterns, commonly found in the 1 melanoma.
      Local recurrence occurred in 29% of patients and malignant cranial neuropathies
      were documented in 4 patients. Nineteen percent of patients have died from
      disseminated disease. Neurotropic melanomas had a lower incidence of visceral
      recurrence. Desmoplastic and neural transforming melanomas had similar rates of
      local and visceral recurrence. When this specific variant of melanoma is compared
      with larger series of malignant melanoma in general, they appear to be more
      advanced locally, with a higher incidence of local recurrence. When considered in
      relation to the thicker nondesmoplastic melanomas, the survival is no worse and
      may be more favorable. Surgeons should excise the primary tumor and local
      recurrences with wide margins and adopt close follow-up. On the head and neck,
      symptoms and signs relating to trigeminal or facial nerve innervation may herald
      a developing malignant cranial neuropathy.

PMID- 1373258
TI  - Palliative care and melanoma: the care of the patient with progressive disease.
AB  - The World Health Organization has taken the lead in recent years in encouraging
      an appropriate focus on palliative care which includes but goes beyond terminal
      care. Comprehensive care of patients with advanced progressive disease requires
      increased emphasis, with adequate resources. Management of major symptoms is a
      crucial component of such a care program and requires the application of recent
      advances in palliative therapeutics (notably but not only good quality pain
      management), whether or not direct antitumor strategies are being continued. The
      choice of treatment approaches must be related to the patient's personal
      priorities.

PMID- 1373259
TI  - Palliative operative procedures for carcinoma of the gallbladder.

PMID- 1373260
TI  - Macromolecular self-association of a synthetic peptide derived from the hepatitis
      B surface antigen: construction of a quaternary epitope.
AB  - A major impediment to the development of peptide vaccines has been the inability
      accurately to mimic conformationally constrained epitopes on the envelope
      proteins of pathogens. This limitation is further compounded by the fact that
      several viral envelope proteins exist either as covalently or non-covalently
      associated homo-oligomers in the native state. Evidence is now accumulating to
      indicate that, at least in some instances, these homo-oligomers display antigenic
      determinants that are not present in the dissociated monomer units. Clearly this
      problem will have to be addressed if peptide-based vaccines are ever to become
      feasible alternatives. In this report we demonstrate that an oligomerized
      synthetic peptide that was derived from the hepatitis B surface antigen
      aggregates in solution to form macromolecular structures. These aggregates appear
      to represent a 'native' form of the group-specific determinant presented by the
      hepatitis B surface antigen.

PMID- 1373261
TI  - Multiple administration with interleukin-2 potentiates antigen-specific responses
      to subunit vaccination with bovine herpesvirus-1 glycoprotein IV.
AB  - Interleukin-2 has been described as an effective adjuvant for a number of
      antigens in different host species. Previously, we demonstrated the adjuvant
      activity of recombinant bovine IL-2 with a glycoprotein IV (gIV) subunit vaccine
      from bovine herpesvirus type-1 (BHV-1). In the present study, primary antibody
      responses were assessed in cattle immunized with either 2 or 50 micrograms of
      gIV, and treated with multiple doses of IL-2 or combinations of IL-2 and IFN
      alpha or IL-2 and IFN-gamma. IL-2 was able to augment significantly antibody
      responses detected by either ELISA or virus neutralization. More significantly,
      IL-2 was able to enhance antibody titres in animals immunized with only 2
      micrograms gIV to levels similar to those immunized with 50 micrograms gIV in the
      absence of IL-2. For optimal stimulation, multiple injections of IL-2 and
      Avridine had to be used in the formulation; other oil adjuvants or IL-2 alone
      could not induce a primary serum antibody response. Addition of IFN-alpha or IFN
      gamma to the IL-2/gIV/Avridine formulation did not affect any of the immune
      parameters tested. As IFN-alpha is an effective immunoprophylactic agent for
      infectious bovine rhinotracheitis (IBR), combination vaccine-immunoprophylaxis
      may become feasible using IL-2 as a co-adjuvant. Thus, extremely low doses of
      antigen and only one immunization may be an effective vaccine given in
      combination with interferon prophylactic treatment.

PMID- 1373262
TI  - Expression of foreign epitopes on recombinant occlusion bodies of baculoviruses.
AB  - Recombinant polyhedrin proteins of the baculovirus Autographa californica nuclear
      polyhedrosis virus were constructed to serve as immunologic carriers of foreign
      epitopes. Several recombinants containing an influenza haemagglutinin epitope
      were obtained. Three of the five recombinants formed occlusion bodies (OBs) and
      two did not. All of the recombinant polyhedrin proteins reacted with a monoclonal
      antibody (mAb) specific for an influenza epitope in Western blots. Presentation
      of the foreign epitope on the surface of recombinant OBs was demonstrated by
      specific immunoprecipitation of the anti-influenza mAb with recombinant OBs. The
      recombinant polyhedrin-influenza epitope fusion protein stimulated an influenza
      specific immune response in rabbits.

PMID- 1373263
TI  - Histochemical demonstration of gastrointestinal mucins in ovarian mucinous
      cystadenoma.
AB  - Forty-one specimens of mucinous cystadenoma (MCA) of the ovary and 13 specimens
      of normal uterine endocervix were investigated histochemically using alcian blue
      pH 2.5-PAS, high iron diamine-alcian blue pH 2.5, galactose oxidase-Schiff
      reaction (GOS, for detection of gastric surface mucous cell mucins), paradoxical
      Concanavalin A staining (PCS, for detection of gastric gland cell mucins) and
      periodic acid-sodium borohydride-potassium hydroxide-PAS (PA-SB-PH-PAS) reaction
      (for detection of mucins of the large intestine). In addition, Grimelius staining
      was carried out to explore the distribution of endocrine cells. The MCAs
      contained abundant neutral mucins but a little acid mucins, whereas sulfomucins
      predominated in normal endocervices. Among the MCAs, 30, 26, 2 and 9 had tumor
      cells positive for GOS, PCS, PA-SB-PH-PAS and Grimelius stain, respectively.
      These results indicate that MCAs frequently contain tumor cells of the
      gastrointestinal type and endocrine cell type. Endocervical epithelia, on the
      other hand, lack reactivity for PCS, PA-SB-PH-PAS and Grimelius stain, although
      in 8 of the present specimens, the lining cells showed weak GOS reactivity.

PMID- 1373264
TI  - Immunoreactive copper-zinc superoxide dismutase in damaged human myocardium.
AB  - The myocardium in 50 autopsy cases was studied using immunostaining for copper
      zinc superoxide dismutase (CuZn-SOD) and standard histochemical procedures.
      Mucinous degeneration observed in 42 cases showed moderately enhanced expression
      of immunoreactive CuZn-SOD in lesions which were stained strongly by periodic
      acid-Schiff but negative with Heidenhain iron-hematoxylin (HIH), von Kossa and
      luxol fast blue (LFB) stains, whereas coagulation necrosis in 4 cases revealed
      almost identical immunostaining for CuZn-SOD and HIH to that of contraction band
      necrosis, i.e. strongly positive HIH staining but negative immunostaining.
      Basophilic alteration of the myocardial cells in sections fixed with 4% formalin
      in 2% calcium acetate was seen in 29 cases, being identified frequently in
      isolated cells as well as in several foci varying considerably in size. This type
      of alteration demonstrated significantly enhanced expression of immunoreactive
      CuZn-SOD and was strongly positive with von Kossa and LFB stains. The present
      study indicates that the myocardium can be affected by free radicals produced in
      any organ of the body, and that subsequently, insoluble phospholipids react with
      calcium ions in the fixative and accumulate in the basophilic sarcoplasm.

PMID- 1373265
TI  - Sensitivity and accuracy of a bio-assay for the determination of the
      concentration of residual pesticide in natural water bodies.
AB  - Determination of pesticide levels in natural water bodies requires complex
      chemical methods not always available in tropical countries where such control
      programmes are implemented. Apart from chemical methods, effectiveness of
      treatment can be estimated by mortality of target and non-target species. But the
      latter criteria do not permit a good appraisal of dispersion and residual
      activity of pesticide. We propose here a simple and cheap bio-assay adaptable to
      water-borne vector or intermediate host control programmes. Results obtained with
      the bio-assay were compared with those obtained with gas liquid chromatography, a
      standard chemical method.

PMID- 1373266
TI  - Effects of left ventricular dysfunction on the circadian variation of ventricular
      premature complexes in healed myocardial infarction.
AB  - Circadian variation in the onset of cardiovascular events including sudden
      cardiac death, myocardial infarction and ventricular arrhythmias has been
      described. The effect of left ventricular (LV) dysfunction on the circadian
      variation of ventricular premature complex (VPC) frequency was evaluated in 132
      patients with frequent VPCs and reduced LV function after myocardial infarction.
      Patients were prospectively divided in 2 groups based on LV ejection fraction
      (EF) (those with LVEF less than or equal to 0.30, and those with LVEF between
      0.30 and 0.45). Median hourly VPC frequencies and heart rates were compared
      between the 2 groups. Subgroup analyses based on treatment with beta-adrenoceptor
      blocking agents and on New York Heart Association functional class were also
      performed. In patients with LVEF greater than 0.30, a distinct circadian
      variation of VPCs, and the expected morning increase in VPC frequency were
      present. In contrast, a distinct circadian variation of VPCs was absent in
      patients with LVEF less than or equal to 0.30. A circadian variation of VPC
      frequency was also absent in patients with severe symptomatic congestive heart
      failure (New York Heart Association class III-IV). Treatment with beta
      adrenoceptor blocking agents was associated with a loss of the circadian
      variation of VPC frequency. The circadian variation of heart rate was also
      blunted in the group treated with beta-adrenoceptor blocking agents. The
      proportion of subjects manifesting a positive correlation between heart rate and
      VPC frequency was lower in subjects with LVEF less than or equal to 0.30 (26%)
      than in those with LVEF greater than 0.30 (46%) (p less than 0.05). Thus,
      circadian variation of VPC frequency is absent in patients with severe LV
      dysfunction.

PMID- 1373267
TI  - Molecular biology of African trypanosomes: development of new strategies to
      combat an old disease.
AB  - African trypanosomes are protozoan parasites that cause a number of diseases of
      man and domesticated animals in large regions of sub-Saharan Africa. The diseases
      have proven to be particularly difficult to prevent or to effectively treat due
      to features of both the trypanosome and the insect vector, the tsetse fly. The
      habitat of the tsetse and its resistance to insecticides have rendered vector
      control efforts ineffective. Attempts to develop a vaccine against the African
      trypanosomes has been dwarfed by the parasite's ability to change the composition
      of its exposed surface antigens. This process of antigenic variation allows the
      parasite to avoid the host's immune response and presents the host with a
      seemingly endless antigenic repertoire. Since conventional approaches to the
      control of African trypanosomiasis have largely met with failure, there has been
      a renewed interest in identifying novel aspects of the biology, biochemistry, and
      molecular biology of trypanosomes that might be exploited to develop new targets
      for vaccines or chemotherapy. Importantly, this research has opened a virtual
      Pandora's box of exciting biochemical and molecular surprises, which makes the
      African trypanosomes not only important medical pathogens but also an exciting
      experimental system for the basic scientist. In this review, the authors will
      describe some of the most recent and intriguing developments in the field of
      molecular parasitology.

PMID- 1373268
TI  - Expression of endothelial adhesion molecules in vivo. Increased endothelial ICAM
      2 expression in lymphoid malignancies.
AB  - The authors have compared the reactivity of monoclonal antibodies (MAb) directed
      against endothelial adhesion molecules (ICAM-1, ICAM-2, VCAM-1, ELAM-1) in
      hyperplastic, nonmalignant, and malignant lymph nodes. The authors demonstrate
      that the reactivity with ICAM-1 MAb is stronger in the high endothelial venules
      (HEV) and other smaller vessels (SV) in lymphomas compared with hyperplastic
      lymph nodes. Similarly, the reactivity of an ICAM-2 MAb (6D5) was shown to be
      higher in malignant lymph nodes compared with nonmalignant ones. ICAM-2 MAb
      stained both the HEV and SV. VCAM-1 MAb reacted strongly with germinal centers
      and its endothelial reactivity was higher in the lymphoma nodes. ELAM-1 MAb
      stained only faintly some endothelial cells in malignant tissue. These data
      suggest that besides the known regulatable endothelial adhesion molecules ICAM-1
      and VCAM-1, the expression of ICAM-2 can be modified.

PMID- 1373269
TI  - The AMeX method: a multipurpose tissue-processing and paraffin-embedding method.
      Extraction of protein and application to immunoblotting.
AB  - The authors have previously reported a new fixation and paraffin-embedding method
      (the AMeX method), which preserves many antigens as well as high molecular-weight
      DNA and RNA that are normally destroyed by the routine formalin fixation and
      paraffin-embedding process. In the present study, the authors analyzed the
      preservation of protein suitable for sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and immunoblotting in tissue fixed by the AMeX method.
      The method used for extraction of protein from AMeX-processed tissue sections
      after deparaffinization was the same as that for extraction from fresh tissues.
      The total amount of protein extracted from 50-mg (wet weight) AMeX-processed
      mouse liver tissue was the same as that from fresh tissue. The electrophoretic
      mobility and staining intensity of protein on SDS-polyacrylamide gel, and the
      immunoblotting pattern and staining intensity with several antibodies, were
      identical for both AMeX-processed and fresh tissue. Degradation of protein was
      minimal for storage periods of 2 years in paraffin block. The authors also showed
      that pellets of cultured cells can be processed by this method for immunologic
      analysis. This new fixation and paraffin-embedding method is a useful tool for
      obtaining information on correlations between morphologic features and
      immunochemical and molecular biological data.

PMID- 1373270
TI  - Accumulation of amyloid precursor protein in neurons after intraventricular
      injection of colchicine.
AB  - To study a possible relationship between inhibition of axonal flow and
      amyloidogenesis, the authors examined amyloid precursor protein (APP)
      immunoreactivity in rat brain treated with colchicine. After intraventricular
      injection of colchicine, the proximal axons of exposed neurons became swollen and
      showed a large increase in APP immunoreactivity, whereas the cytoplasm and
      dendritic processes showed lesser increases. These changes were seen in
      ipsilateral neurons of the hippocampus, lateral septal nucleus, amygdala, and
      entorhinal, parietal and temporal cortices, as well as bilaterally in the
      periventricular hypothalamic nucleus. The increase of APP immunoreactivity
      appeared as early as 3 hours after the injection. It peaked at around 24 hours,
      and began to clear after about 4 days. A few strongly APP-positive dystrophic
      neurons remained. In serial sections at these later time periods, some strongly
      argentophilic neurons and Alz-50 positive neurons, each with abnormal neurities,
      could be demonstrated. The result suggests that APP may undergo fast axoplasmic
      flow in rat brain and that argentophilic changes of Alz-50 immunoproduction may
      follow APP accumulation caused by inhibition of axoplasmic flow.

PMID- 1373271
TI  - Activation of the contact system in lethal hypotensive bacteremia in a baboon
      model.
AB  - The hypotension in septicemia is believed to be mediated by the combined action
      of many mediators including cytokines, prostaglandins, and complement components.
      To evaluate the contribution of the contact/kinin-forming system to hypotension,
      the authors used an established experimental baboon model of bacteremia in which
      two concentrations of Escherichia Coli (E. coli) were used to produce lethal and
      nonlethal hypotension. The lethal group (n = 5) developed irreversible
      hypotension that significantly correlated with the decline in levels of high
      molecular weight kininogen (HK) and an increase in alpha 2 macroglobulin
      kallikrein complexes (alpha 2M-kal). The nonlethal group (n = 9) experienced
      reversible hypotension, a less striking decline in HK, and only slight elevation
      in alpha 2M-kal. No significant changes were found in levels of factor XII,
      prekallikrein, and factor XI in either group. A significant change in the contact
      system, which reflects the fatal outcome, is the rise in alpha 2M-kal. This study
      suggests that irreversible hypotension correlates with prolonged activation of
      the contact system.

PMID- 1373273
TI  - Multiple ionic mechanisms of early afterdepolarizations in isolated ventricular
      myocytes from guinea-pig hearts.
AB  - Ionic mechanisms of early afterdepolarization (EAD) induced by the K(+)-free
      solution or veratridine were studied with guinea-pig ventricular myocytes using
      the patch-clamp technique of whole-cell and cell-attached patch configurations.
      In the K(+)-free solution, myocytes exhibited prolonged action potential duration
      with humps on the final repolarization phase, which eventually turned into EAD
      starting around -70 mV and induced triggered activity. Application of 0.5 mM Cd2+
      inhibited the development of EAD and caused depolarization of maximum diastolic
      potentials around -30 mV, although Cd2+ did not prevent prolongation of the
      action potential. Application of 50-100 microM Ni2+ or 30 microM tetrodotoxin had
      little effects on EAD and diastolic potentials. The background current-voltage
      relation examined by a ramp voltage clamp showed inhibition of the inward
      rectifier K+ current, induction of steady inward current between -40 and -10 mV,
      and increase in the outward tail current upon repolarization in the K(+)-free
      solution. Cd2+ completely blocked the steady inward current at the plateau level
      and partially depressed the delayed outward K+ current, while Ni2+ had no effects
      on the background I-V relation. Tetrodotoxin showed a mild inhibitory effect on
      the inward component of the background current negative to -50 mV, but left the
      steady inward current at the plateau level. Therefore, EAD in the K(+)-free
      condition is mainly formed by decreased inward rectifier K+ current, activation
      of the L-type Ca2+ current, and time-dependent decay of the delayed outward K+
      current upon repolarization. Application of 25-100 microM veratridine caused
      marked prolongation of action potential with appearance of regenerative EADs.
      Action potential prolongation and EADs were partially abolished by Cd2+ and
      completely eliminated by tetrodotoxin. The single channel current recordings
      showed a decreased current amplitude, and prolonged and delayed openings of the
      Na+ channel currents by veratridine. Thus, an ensemble average current showed
      markedly prolonged decay time constant of 609 msec in veratridine from 3.6 msec
      in the control. These results indicate that veratridine-induced EAD is mainly
      formed by altered properties of the Na+ channel current and partly by the L-type
      Ca2+ current due to slowed repolarization. Thus, EAD can be induced by different
      ionic mechanisms depending on the basal conditions.

PMID- 1373272
TI  - Massive accumulation of modified tau and severe depletion of normal tau
      characterize the cerebral cortex and white matter of Alzheimer's disease.
      Demonstration using the hydrated autoclaving method.
AB  - Using the hydrated autoclaving method, a new immunohistochemical procedure to
      enhance tau immunoreactivity in formalin-fixed brain tissue, the authors recently
      reported that tau protein is detected in neuronal cell bodies and proximal
      dendrites, gray matter neuropil, axons, and glial cells in normal human
      hippocampus and neocortex. In the this study, the authors performed a comparative
      study of the distribution of normal and modified forms of tau in Alzheimer's
      disease (AD) and control brains. In the cerebral cortex and white matter of AD
      brains, a massive accumulation of modified tau and/or severe depletion of normal
      tau were documented in all the tau compartments. In mild AD cases, gray matter
      neuropil, axons, and glial cells were less severely involved than neuronal
      perikarya. In the controls, neuronal perikarya were often involved by modified
      tau accumulation, but the other compartments showed normal distribution. These
      observations suggest that modifications of tau which lead to neurofibrillary
      lesions in AD may begin in neuronal perikarya and extend to the other tau
      compartments in advanced stages of the disease.

PMID- 1373274
TI  - [Cell movement in the skin].

PMID- 1373275
TI  - [Treatment of metastatic melanoma with interleukin-2].

PMID- 1373276
TI  - [1492-1992: 500 years ago Christopher Columbus rediscovered America. From the
      rediscovery of skin diseases already described].

PMID- 1373277
TI  - Mechanotransduction.

PMID- 1373278
TI  - Adenosine receptors.
AB  - Our knowledge of A1 and A2ARs has grown dramatically since they were first
      defined by Burnstock. With the recent purification of the A1AR and the cDNA
      cloning of the A2AR, an even more rapid expansion of information regarding their
      structure, function, and regulation should now ensue. We may then be able to
      return to the intact cell and organ system and better understand the
      physiological role of these ubiquitous receptors.

PMID- 1373279
TI  - Chemosensory transduction mechanisms in taste.

PMID- 1373280
TI  - Water channels in cell membranes.

PMID- 1373281
TI  - Porcine retrovirus: optimal conditions for its biochemical detection.
AB  - The assay of reverse transcriptase (RT) activity was used to detect the presence
      of retrovirus in porcine cells. A set of optimal assay conditions was determined
      to design a sensitive, quantitative and reproducible RT assay for porcine
      systems. The template-primer poly(rA).oligo(dT) was an absolute requirement. The
      presence of Mn++ was indispensable, with an optimal concentration of 0.25 mM.
      Monocations (K+, Na+) at 50 mM greatly enhanced, but their high doses inhibited
      the reaction. The pH of the medium influenced very much the reaction, especially
      with non-purified virus samples, with which the RT activity was inhibited at pHs
      above 8.2. Non-ionic detergents at 1% enhanced several-fold the RT activity. It
      was also shown that porcine retrovirus could be spontaneously reactivated in
      porcine cell lines by in vitro long-term propagation and transmitted to pigs by
      inoculation with virus-producing cells.

PMID- 1373282
TI  - Expression of a hepatitis E virus (HEV)-trpE fusion protein containing epitopes
      recognized by antibodies in sera from human cases and experimentally infected
      primates.
AB  - A 1700 base cDNA fragment coding for the putative structural gene(s) of hepatitis
      E virus (HEV) was inserted into the pATH 10 expression vector. The fusion protein
      (C2) expressed by this plasmid was found to contain epitopes recognized by anti
      HEV antibodies. C2 protein was used in a Western blot format to examine its
      usefulness in detecting anti-HEV antibodies in well documented human cases of HEV
      and non-human primates infected with HEV. Both IgM and IgG anti-HEV could be
      detected in our Western blot assay. This Western blot assay was found not to
      detect antibodies from acute-phase sera from patients with either HAV or HBV. The
      C2 protein contains broadly cross-reactive epitopes, and the Western blot assay
      was able to detect anti-HEV antibodies in patient sera from Asia, Africa, and
      North America. The optimum serum dilution for the detection of both IgM and IgG
      was 1:25.

PMID- 1373284
TI  - Cold resistance estimated on the basis of fetal hemoglobin changes during acute
      general cooling.
AB  - In order to find a criterion for human cold resistance and adaptability we
      studied the reaction of hematological indices to acute general cooling of the
      whole organism (12 degrees C, 1 h) in 60 male volunteers 19-25 years old living
      in Norilsk (69 degrees N) for about 2 1/2 years. The first group of subjects
      comprised of cold adapted individuals whose professional activity was associated
      with 4-5 hrs daily work outdoor in cold environment. The volunteers of the second
      group regularly worked indoor and are considered a priori cold unadapted. Our
      results indicate that fetal hemoglobin (HbF) concentration shows the most
      remarkable reaction to acute cooling in comparison with other parameters studied
      (erythrocyte count, hematocrit, total hemoglobin level). Cold exposure of
      unadapted young males was accompanied by a marked increase of HbF concentration
      in venous blood (from 1.27 +/- 0.13% to 2.04 +/- 0.02%, p less than 0.01),
      whereas the same procedure in the adapted subjects was followed by practically
      unchanged HbF levels. These findings lead us to the conclusion, that the change
      of the HbF level under acute general cooling can be considered a satisfactory
      criterion of human cold resistance.

PMID- 1373283
TI  - HIV-1 reverse transcriptase inhibition by a dipyridodiazepinone derivative: BI-RG
      587.
AB  - The dipyridodiazepinone derivative 6,11-dihydro-11-cyclopropyl-4
      methyldipyrido[2,3-b:2',3'-e]-[1,4] diazepin-6-one (BI-RG-587) selectively
      inhibits human immunodeficiency virus type 1 (HIV-1) replication by suppressing
      HIV-1 reverse transcriptase activity. Both RNA- and DNA-dependent polymerase
      associated activities of this enzyme were found to be inhibited by BI-RG-587 in a
      pattern dependent on the template used. The lowest IC50 values were obtained
      using poly(rC)-oligo(dG)12-18 and poly(dA)-oligo(dT)12-18 as template-primer. For
      the RNA-dependent activity poly(rC)-oligo(dG)12-18 and dGTP appeared to enhance
      the inhibition of the RNA-dependent enzyme activity by BI-RG-587, with the effect
      of poly(rC)-oligo(dG)12-18 dominating that of dGTP. Poly(rA)-oligo(dT)10 seemed
      to decrease the inhibition whereas poly(rU)-oligo(dA)12-18 or poly(rG)-oligo
      (dC)12-18 had no effect. dATP, dTTP and dCTP, three nucleotide triphosphates,
      also had no impact on the inhibition. Differences were observed for the template
      dependent action of BI-RG-587 against the DNA-dependent enzyme activity. Both
      substrates were required to allow the inhibition by BI-RG-587 in the poly(dC)
      oligo(dG)12-18 and dGTP reaction, whereas only the template and enzyme
      interaction seemed to be necessary for the poly(dA)-oligo(dT)12-18 and dTTP
      reaction. The different behaviors of DNA- and RNA-dependent DNA polymerase
      activities could indicate either the presence of different active sites for
      distinct activities or the presence of a unique active site with different
      configurations depending upon the template used. Also, BI-RG-587 showed a
      mutually exclusive inhibition when combined with two other classes of HIV-1 RT
      inhibitors represented by phosphonoformic acid and 3'-azido-3'-dideoxythymidine
      triphosphate.

PMID- 1373285
TI  - Leukocyte traffic to sites of inflammation.
AB  - The adhesion of circulating leukocytes to the vascular endothelium is essential
      for effective host inflammatory and immune responses. Adhesion proteins expressed
      by both the leukocyte and endothelial cell have been well characterized, and
      studies of these molecules have shown that both cell types are actively involved
      in regulating these binding events. Most leukocyte (leukocyte integrins) and
      endothelial cell (vascular selectins, ICAM-1, and VCAM) adhesion proteins
      increase in expression and function in response to mediators released by inflamed
      tissues. In contrast, the expression and function of one type of leukocyte
      molecule, L-selectin (previously called LECAM-1, LAM-1, gp90MEL-14), is "down
      regulated" by inflammatory signals. The purpose of this review is to summarize in
      vitro and in vivo regulatory and functional studies of some of the molecular
      mechanisms which regulate leukocyte-endothelial cell adhesion, with particular
      emphasis on L-selectin, and to present a hypothetical model of how these
      molecules may be orchestrated in vivo resulting in the control of host
      inflammatory responses.

PMID- 1373286
TI  - Antigenic structure of the herpes simplex virus type 1 glycoprotein C:
      demonstration of a linear epitope situated in an environment of highly
      conformation-dependent epitopes.
AB  - A continuous epitope, situated within or in close proximity to antigenic site II
      of the herpes simplex virus type 1-specified glycoprotein C (gC-1), was
      identified. The continuous linear nature of the epitope, defined by a monoclonal
      antibody C2H12, was established by three independent lines of evidence: (i) The
      epitope was detectable by immunoblot under denaturing and reducing conditions.
      (ii) The epitope was detectable by RIPA of extracts from TM-treated HSV-infected
      cells, despite the malfolding caused by this treatment. (iii) The epitope was
      detected in an approximately 5,000-dalton papain fragment of gC-1. A mapping
      analysis, primarily based on use of mutant virus, expressing truncated gC-1
      molecules, suggested that the mapping position of the epitope was delimited by
      amino acids 120 and 230. Other epitopes of this region of gC-1 are highly
      conformation-dependent, and the existence of a linear epitope, accessible on
      native gC-1, may facilitate the elucidation of the functional anatomy of gC-1.

PMID- 1373287
TI  - Clinical pharmacology of mivacurium chloride: a review.
AB  - Mivacurium chloride (Mivacron) is a new benzylisoquinolinium choline-like diester
      neuromuscular blocking drug with an onset of action at equipotent doses that is
      comparable to atracurium and vecuronium but slower than succinylcholine. Its
      clinical duration (injection-25% recovery and injection-95% recovery) is twice
      that of succinylcholine but one-half to one-third that of atracurium and
      vecuronium. Mivacurium is easy to use as a continuous infusion and when used this
      way its recovery characteristics are unchanged. It is readily antagonized by
      anticholinesterase drugs. The ED95 in adults under narcotic-based anesthesia is
      0.07-0.08 mg/kg. At twice the ED95 (0.15 mg/kg) onset time is about 2 to 3
      minutes, duration to 25% recovery is 15 to 20 minutes, and 5-95% recovery time
      about 14 minutes. The mean infusion rate in adults is 6 micrograms/kg/min (range
      2-15) with a 5-95% recovery time of 14 minutes. Enflurane and isoflurane require
      a 20-30% decrease in dosage; halothane, enflurane, and isoflurane prolong the
      duration of mivacurium 25-30%. The ED95 in children 2 to 12 years of age is
      slightly higher (0.09-0.11 mg/kg) with a faster onset and shorter duration. In
      these young patients, a dose of 0.2 mg/kg has an onset comparable to
      succinylcholine. Being chemically related to atracurium, mivacurium may cause
      histamine release. When administered rapidly at doses of 0.2 mg/kg or greater in
      adults, histamine release and transient hypotension have been observed. Doses of
      0.2 mg/kg or higher are not recommended by the manufacturer. Mivacurium is
      metabolized by plasma cholinesterase. In vitro, the rate is about 70% that of
      succinylcholine. In patients with normal or slightly less than normal plasma
      cholinesterase activity, no prolonged durations of action have been observed. In
      patients heterozygous for the atypical gene and at a dose of 0.2 mg/kg, 50%
      prolongation has been shown. Those individuals homozygous for the atypical gene
      are exquisitely sensitive to mivacurium and have a markedly prolonged blockade
      that is readily reversible. In these patients and those with acquired
      deficiencies, mivacurium should not be used. The duration of action in elderly
      patients is comparable to that in the young, while in prerenal transplant
      patients, its duration is prolonged by about 50%, and in prehepatic transplant
      patients, duration of block is increased threefold. Mivacurium possesses the
      advantages of short duration, unchanged recovery characteristics following
      infusions (without phase II block or tachyphylaxis), and precise
      control.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373288
TI  - [Inhibition of neovascularization and tumor growth by dexamethasone].
AB  - It has been proposed that angiogenesis inhibitors should be used for the
      treatment of diseases accompanied by an uncontrolled angiogenic response,
      particularly such disease occurring during progressive growth of solid tumors. In
      this study, the antiangiogenic effect of dexamethasone (DEX) was studied in a
      system using chorioallantoic membranes (CAM) of fertilized eggs and rabbit
      corneas. First, DEX was examined for its effect on embryonic angiogenesis using
      4, 5 day old CAMs of chick embryos. After the shell and shell membrane was
      removed, an EV pellet with or without DEX was placed within a silicon ring. Two
      days later, the antiangiogenic response was evaluated by measuring the avascular
      zone of the CAM beneath the pellet. When the CAM showed an avascular zone of 3 mm
      or more in diameter, the response was scored as positive. DEX showed potent
      antiangiogenic activity and produced an avascular zone in 100% of CAMs at the
      highest dose tested. (250 ng/egg). Next, inhibitory effect of vascularization and
      tumor growth by local implant of DEX was observed in a rabbit cornea assay. An
      intra-corneal pocket extending to within 1 mm of the limbus was used to house a 1
      mm3 piece of glioma. In the treatment group, DEX-containing EV pellet was
      inserted between the limbus and glioma. Ten days after the implantation of glioma
      and EV pellet, vascular response and tumor growth was evaluated. For morphologic
      studies, the excised corneas were fixed with formaldehyde fixative and sectioned
      for light microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373289
TI  - Topology of the anion-selective porin Omp32 from Comamonas acidovorans.
AB  - Limited proteolysis experiments were performed with outer membranes from
      Comamonas acidovorans to probe the topology of its major protein component, the
      anion-selective porin Omp32. Proteinase K treatment above a critical temperature
      of 42 degrees C cleaved the surface-exposed regions of the porin, yielding
      membrane-embedded fragments which were separated by SDS polyacrylamide gel
      electrophoresis or reversed phase chromatography. The identification of the
      proteinase K-sensitive sites was performed by microsequencing. This allowed us to
      determine six surface-exposed sites of the porin, all located in nonconserved
      primary structure regions. These results along with the previously determined
      amino acid sequence and in conjunction with some structural constraints
      applicable to porins allowed us to propose a chain-folding model of the Omp32
      porin. The features of our model are compared with the structure of the
      Rhodobacter capsulatus porin, recently established by X-ray crystallography
      (Weiss et al., 1991) and they are used to elucidate the structural basis of the
      anion selectivity.

PMID- 1373290
TI  - Localization of interferon-induced lupus inclusions demonstrated by computer
      image reconstruction of monensin-treated Daudi cells.
AB  - A structural analysis of cells that contained the interferon-alpha-induced lupus
      inclusions (LI) was performed using a high-voltage electron microscope to
      determine the exact cellular location of LI and their association with normal
      cell organelles. LI were induced in the human B lymphoblastoid cell line, Daudi,
      by culturing with the pure recombinant human leukocyte interferon, IFLrA. Just
      prior to harvesting, a portion of the cells was treated with monensin to
      selectively swell the Golgi apparatus, and thereby simplify their identification
      using the electron microscope. Organellar associations between LI and the outer
      nuclear envelope and Golgi apparatus were identified in stereopairs of 1-micron
      sections prepared from both cells that were not treated with monensin and those
      that were treated with monensin. Serial 0.25-micron sections of the monensin
      treated cells were prepared, and seven arbitrarily chosen cells were examined.
      Each of these cells contained a single LI, and it formed throughout an
      endoplasmic-reticulum region that made contact with both the outer nuclear
      envelope and the Golgi vesicles. Reconstruction of a cell by computer from the
      digitized negatives of serial sections clearly illustrated these relationships.
      This study reports the first determination of the association between LI and the
      Golgi apparatus. It also identifies the presence of only one LI in every cell,
      and the routine association of the LI with both the outer nuclear envelope and
      the Golgi apparatus. The unique cell location of LI formation suggests their
      functioning in membrane biogenesis, the trafficking of proteins to the plasma
      membrane or to cytoplasmic vesicles, or the processing of proteins for secretion.

PMID- 1373291
TI  - Domain structure and antiparallel dimers of microtubule-associated protein 2
      (MAP2).
AB  - We have studied the microtubule-associated protein MAP2 from porcine brain and
      its subfragments by limited proteolysis, antibody labeling, and electron
      microscopy. Two major chymotryptic fragments start at lys 1528 and arg 1664,
      generating microtubule-binding fragments of Mr 36 kDa (303 residues, analogous to
      the "assembly domain" of Vallee, 1980) and 18 kDa (167 residues). These fragments
      can be labeled with the antibody 2-4 which recognizes the last internal repeat of
      MAP2 (Dingus et al., 1991). The epitope of another monoclonal antibody, AP18
      (Binder et al., 1986), was mapped to the first 151 residues of MAP2. The
      interaction with AP18 is phosphorylation dependent; dephosphorylated MAP2 is not
      recognized. Intact MAP2 forms rod-like particles of 97 nm mean length, similar to
      Gottlieb and Murphy's (1985) observations. Both antibodies bind near an end of
      the rod, suggesting that the sequence and the structure are approximately
      colinear. There is a pronounced tendency for MAP2 to form dimers whose components
      are nearly in register but of opposite polarity. MAP2 can also fold in a hairpin
      like fashion, generating 50-nm rods, and it can self-associate into oligomers and
      fibers. The 36-kDa microtubule-binding fragment also has a rod-like shape; its
      mean length is 49 nm, half of the intact molecule, even though the fragment
      contains only one-sixth of the mass. The antibody 2-4 decorates one end of the
      rod, similar to the intact protein. The fragment also forms antiparallel dimers,
      but its tendency for higher self-assembly forms is much lower than with intact
      MAP2.

PMID- 1373292
TI  - IL-1 production as a regulator of G-CSF and IL-6 production in CSF-producing cell
      lines.
AB  - We previously demonstrated that colony stimulating factor (CSF)-producing cell
      lines co-produce interleukin-1 (IL-1) and IL-6 in addition to CSFs. In the
      present study, we examined the role of IL-1 production in three human tumour cell
      lines producing granulocyte (G)-CSF, IL-1 and IL-6. Addition of anti-human IL-1
      alpha antiserum to the culture caused a 90-62% reduction of G-CSF and a 85-44%
      reduction of IL-6 production, respectively, as evaluated by enzyme immunoassay in
      all three cell lines. The decrease of G-CSF and IL-6 production by the anti-IL-1
      alpha antiserum was also confirmed at the level of mRNA expression. The anti-IL-1
      alpha antiserum did not affect the growth of these cell lines. Excess recombinant
      IL-1 alpha exogenously added to the culture enhanced G-CSF and IL-6 production in
      all three cell lines. However, IL-1 alpha had little effect on the growth of
      these three cell lines. Neither anti-IL-6 nor anti-G-CSF antibodies affected the
      production of the other cytokines. These results indicate that IL-1 alpha
      regulates G-CSF and IL-6 production in these tumour cell lines, and suggest that
      the IL-1 production plays an important role in CSF-producing tumours.

PMID- 1373293
TI  - Effectiveness of combinations of bispecific antibodies for delivering saporin to
      human acute T-cell lymphoblastic leukaemia cell lines via CD7 and CD38 as
      cellular target molecules.
AB  - We have investigated the effectiveness of three different F(ab' gamma)2
      bispecific antibodies (BsAb) for delivering the ribosome inactivating protein
      (RIP) saporin via the CD7 or CD38 cell surface molecules to the human T-ALL cell
      lines HSB-2 and HPB-ALL. Inhibition of 3H-leucine uptake by target cells was used
      as the parameter of cellular cytotoxicity. Used singly against HSB-2 cells in the
      presence of varied concentrations of saporin, an anti-CD7 BsAb, (HB2 x DB7-18)
      and an anti-CD38 BsAb (OKT10 x RabSap), gave 435- and 286-fold increases in
      saporin toxicity, respectively. For HPB-ALL cells the anti-CD7 BsAb performed
      poorly giving only an eight-fold increase in toxicity whilst on the same cell
      line the anti-CD38 BsAb was highly potent giving an 80,000-fold increase in
      saporin toxicity. A combination of both BsAb used together against HSB-2 cells
      was ten times more effective, than the best single BsAb HB2 x DB7-18 used alone.
      Kinetic studies conducted with HSB-2 cells revealed that the BsAb combination
      also gave an increased rate of protein synthesis inactivation in comparison to
      either BsAb used alone. These investigations clearly demonstrate a synergistic
      action when both BsAb are used in combination to target saporin against CD7 and
      CD38 expressed on the surface of the HSB-2 cell line.

PMID- 1373294
TI  - Monoclonal antibody FW6 generated against a mucin-carbohydrate of human amniotic
      fluid recognises a colonic tumour-associated epitope.
AB  - Mucus glycoproteins of human amniotic fluid were used to generate a monoclonal
      antibody (MAb) FW6, which stained the intestine of a 24 week stage fetus. In
      adults, 76% of colonic adenocarcinomas (13/17) showed strong expression of the
      FW6 epitope, but it was not detected in the histologically normal mucosae
      adjacent to the tumours or in normal left colon mucosa. In addition, MAb FW6
      stained large cell carcinomas of the lung (2/3), gastric carcinomas (5/11), and
      ovary adenocarcinomas (3/4). The expression in carcinomas can also be called
      ectopic for testing normal tissues. MAb FW6 was also reactive with pyloric mucus
      glands, Brunner's glands of the duodenum, Paneth cells of the ileum, pancreatic
      ducts, absorptive cells of the right colon, bronchiolar glands, kidney urothelia,
      and with a restricted number of normal mucinous tubuli of salivary gland. It was
      demonstrated to be under the control of the secretion gene only in intestinal
      Paneth cells and absorptive cells of the right colon. Comparative histochemical
      analysis comprising a panel of MAbs suggests that the corresponding epitope of
      the MAb FW6 is a type II chain related carbohydrate structure belonging to the
      Lex/Ley-antigen family, but is different from short chain Lex and Ley.

PMID- 1373295
TI  - Monoclonal antibodies in the detection of bone marrow metastases in small cell
      lung cancer.
AB  - Using conventional examination (CE) of H&E stained slides from bone marrow
      aspirates, metastases can be detected in approximately 25% of patients with small
      cell lung cancer. We investigated a panel of monoclonal antibodies using
      immunohistochemistry in the diagnosis of bone marrow infiltration from SCLC and
      compared the results with CE. Seven monoclonal antibodies raised against
      epithelial antigens (CAM 5.2, MOV 15, NCCST 433, PE 35, LCA1/L38, HMFG 1 AND HMFG
      2) were applied on bone marrow sections from three groups of patients (pts): (1)
      19 pts in whom SCLC-metastases were detected by CE, (2) 44 pts with SCLC in whom
      metastases could not be detected by CE, and (3) 20 pts with non-malignant bone
      marrow diseases. All the antibodies except LCA1/L38 were positive in 60-90% of
      the slides with infiltrating tumour cells in group 1. No positive tumour cells
      were detected in group 2. A few plasma cells and megakaryocytes were slightly
      positive for MOV 15 and NCCST 433, but no other positive cells were detected in
      group 3. In conclusion, the monoclonal antibodies used in this study may be
      useful for diagnostic purposes when a suspicious looking infiltration is detected
      by CE. However, these antibodies could not detect metastatic tumour cells in the
      bone marrow sections from patients in whom CE did not reveal any tumour cells.

PMID- 1373296
TI  - A model of glucocorticoid receptor unfolding and stabilization by a heat shock
      protein complex.
AB  - It has recently been reported that incubation of avian progesterone receptors,
      mouse glucocorticoid receptors, or the viral tyrosine kinase pp60src with rabbit
      reticulocyte lysate reconstitutes their association with the 90 kDa heat shock
      protein, hsp90. The reassociation is thought to require unfolding of the steroid
      receptor or pp60src before hsp90 can bind. The unfoldase activity may be provided
      by hsp70, which is also present in the reconstituted receptor heterocomplex. In
      this paper we review evidence that hsp70 and hsp90 are associated in cytosolic
      heterocomplexes that contain a limited number of other proteins. From an analysis
      of known receptor-hsp interactions and a predicted direct interaction between
      hsp90 and hsp70 we have developed an admittedly very speculative model of
      glucocorticoid receptor unfolding and stabilization. One important feature of the
      model is that the receptor becomes attached to a heat shock protein heterocomplex
      rather than undergoing independent unfolding and stabilization events. The model
      requires that hsp70 and hsp90 bind directly to the receptor at independent sites.
      Importantly, the model accommodates the stoichiometry of 2 hsp90 per 1 molecule
      of receptor that has been assayed in the untransformed GR heterocomplex in
      cytosols prepared from hormone-free cells.

PMID- 1373297
TI  - Steroids inversely affect the biosynthesis and secretion of human prostatic acid
      phosphatase and prostate-specific antigen in the LNCaP cell line.
AB  - In order to elucidate the mechanism of androgen-regulation of genes expressed
      only in the prostate gland, the effects of steroid hormones on the biosynthesis
      and secretion of human prostatic acid phosphatase (PAP) and prostate-specific
      antigen (PSA) were studied in the human prostatic carcinoma cell line, LNCaP.
      This cell line produces PAP and PSA, both of which were found to be similar to
      the proteins purified from and located in human prostatic tissue, as shown by
      Western blot analysis. The synthetic androgen, R1881, regulated the biosynthesis
      of these two important tumour marker proteins inversely: the amount of PSA
      released into the medium was increased to 506% +/- 100 of the control levels,
      while that of PAP was decreased to 26% +/- 3, in 7 days. These effects were
      dependent on the concentration of the steroid in the growth medium. The androgen
      dependent changes observed in the amounts of the secreted proteins were
      correlated with alterations in their intra-cellular levels. LNCaP cells were
      found to have very different capacities for secreting PAP and PSA. Whereas the
      measurable, cellular amounts of PSA and PAP were of similar magnitudes, much
      larger amounts of PSA than PAP were secreted into the medium. PSA was also found
      to be more stable than PAP in the culture medium of the LNCaP cells. Other
      steroids could elicit effects on PAP and PSA biosynthesis similar to those
      induced by R1881, and the combined effects of effective concentrations of these
      steroids were undistinguishable from those caused by each one of them separately,
      suggesting that all these compounds compete for binding to the same modified
      androgen receptors of the LNCaP cells. Thus, our results confirm the observations
      of the altered nature of the LNCaP androgen receptors, and demonstrate the
      ability of these ligands to produce changes in the expression of androgen
      dependent prostatic genes. The fact that the changes observed at the protein
      level were accompanied by increased levels of PSA mRNAs and by decreased levels
      of PAP mRNA in steroid-treated cells, suggests that one of the targets of
      androgen and steroid action in the regulation of these genes is at the mRNA
      level.

PMID- 1373298
TI  - Regulation of tumor-host interactions in breast cancer.
AB  - Breast cancer has a striking dependence upon steroid and other endocrine hormones
      in its onset, regulation, and malignant progression to its most deadly forms. The
      epithelium of the normal mammary gland is also regulated by the ovarian endocrine
      steroids estrogen and progesterone, by other endocrine hormones, and by poorly
      defined influences of the stromal cells and basement membrane. The onset and
      development of cancer appears to involve tumor misinterpretation of and/or
      desensitization to host regulatory signals, and finally to releasing its own
      hormonal signal to reorganize the host for its own benefit. Current studies are
      beginning to examine mediators of tumor-host interaction and their regulation by
      steroid hormones. Important tumor-host interactions under investigation include
      desmoplasia, angiogenesis, metastases and immunosuppression.

PMID- 1373299
TI  - Calcium signaling and secretory responses in agonist-stimulated pituitary
      gonadotrophs.
AB  - In cultured pituitary gonadotrophs, gonadotropin-releasing hormone (GnRH) caused
      dose-dependent and biphasic increases in cytoplasmic calcium concentration
      ([Ca2+]i) and LH release. Both extra- and intracellular calcium pools participate
      in GnRH-induced elevation of [Ca2+]i and LH secretion. The spike phase of the
      [Ca2+]i response represents the primary signal derived predominantly from the
      rapid mobilization of intracellular Ca2+. In contrast, the prolonged phase of the
      Ca2+ signal depends exclusively on Ca2+ entry from the extracellular pool. The
      influx of Ca2+ occurs partially through dihydropyridine-sensitive calcium
      channels. Both [Ca2+]i and LH responses to increasing concentrations of GnRH
      occur over very similar time scales, suggesting that increasing degrees of
      receptor occupancy are transduced into amplitude-modulated Ca2+ responses, which
      in turn activate exocytosis in a linear manner. However, several lines of
      evidence indicated the complexity over the relationship between Ca2+ signaling
      and LH exocytosis. In contrast to [Ca2+]i measurements in cell suspension, single
      cell Ca2+ measurements revealed the existence of a more complicated pattern of
      Ca2+ response to GnRH, with a biphasic response to high agonist doses and
      prominent oscillatory responses to lower GnRH concentrations, with a log-linear
      correlation between GnRH dose and the frequency of Ca2+ spiking. In addition,
      analysis of the magnitudes of the [Ca2+]i and LH responses of gonadotrophs to a
      wide range of GnRH concentrations in the presence and absence of extracellular
      Ca2+, and to K+ and phorbol ester stimulation, showed non-linearity between these
      parameters with amplification of [Ca2+]i-mediated exocytosis. Studies on cell
      depleted of protein kinase C under conditions that did not change the LH pool
      suggested the participation of protein kinase C in this amplification, especially
      during the plateau phase of the secretory response to GnRH.

PMID- 1373300
TI  - Transcriptional activation of jun and actin genes by estrogen during mitogenic
      stimulation of rat uterine cells.
AB  - Estrogens induce transcriptional activation of c-fos and c-myc proto-oncogenes
      during mitogenic stimulation of human, chicken, mouse and rat cells in vivo and
      in vitro. In this paper we show that 17 beta-estradiol injected into adult
      ovariectomized rats increases c-jun, jun-B and jun-D gene transcription in the
      uterus. Kinetics and amplitude of response are different for each gene, since c
      jun is activated first, within 30 min after injection, followed by jun-D and jun
      B, 60 and 90 min after injection, respectively. Maximal activation of jun-B marks
      a drop in transcription of all the jun genes. Furthermore, transcriptional
      activation by 17 beta-estradiol of the growth-regulated beta- and gamma
      cytoskeletal actin genes is prevented by an inhibitor of protein synthesis,
      indicating that it is a secondary response to the hormone. These data support the
      hypothesis that during growth stimulation of target cells the estrogen receptor
      induces transcription of regulatory genes, triggering in this way a cascade of
      gene regulation events that results in progression through the cell cycle.

PMID- 1373301
TI  - Expression of estrogen receptor in the rat brain: detection of its mRNA using
      reverse transcription-polymerase chain reaction.
AB  - Reverse transcription-polymerase chain reaction (RT-PCR)-Southern blotting was
      employed for biochemical detection and measurement of the estrogen receptor
      messenger ribonucleic acid (ERmRNA) in various parts of the Wistar strain female
      rat brain. Total RNA extracted from the tissues was subjected to RT-PCR using the
      primer set which flanked the part(287bp) of the estrogen binding domain
      corresponding region of the rat ERcDNA. It was confirmed that the RT-PCR product
      corresponded to the part of the ERcDNA by direct nucleotide sequencing of the
      product. Moreover, the level of ERmRNA could be determined by Southern blotting
      which was highly sensitive and produced quantitative results. The RT-PCR product
      of about 290 bp, corresponding in length to the distance between two primers, was
      generated from RNA of all the tissues examined. The levels of the product were as
      follows; anterior hypophysis greater than hypothalamus and preoptic area,
      amygdala much greater than cerebral cortex, cerebellum. These results indicate
      that ERmRNA is widely distributed in the whole brain, implying some physiological
      action of estrogen on target and 'non-target' brain regions.

PMID- 1373302
TI  - Expression of progesterone receptor in the neonatal rat brain cortex: detection
      of its mRNA using reverse transcription-polymerase chain reaction.
AB  - Our previous reports have revealed the postnatal developmental pattern of
      progesterone receptor (PR) in the rat cerebral cortex, but little is known about
      PRmRNA changes in the tissue so far. In the present study, we have attempted to
      detect and quantify PRmRNA in the tissue by the use of the reverse transcription
      polymerase chain reaction (RT-PCR)-dot blot analysis. Cerebral cortical tissues
      were dissected from female Wistar rats at 2 and 8 days of age. Total RNA
      extracted from the tissues was reverse transcribed, followed by PCR. The PCR
      primer set, whose sequence was derived from the human clone, flanked the part
      (320 bp) of the human PRcDNA which corresponded to the progesterone binding
      domain. The 320 bp of the RT-PCR product was generated from rat uterine RNA. The
      amino acid sequence deduced from the nucleotide sequence of the product had a
      95.5% identity with the corresponding region in human PR, confirming that the
      product had originated from the rat PRmRNA. Moreover, a highly sensitive and
      quantitative assay for rat PRmRNA had been developed by the use of RT-PCR-dot
      blotting. The PRmRNA was detectable in the cerebral cortex of both 2- and 8-day
      old rats by the assay. Furthermore, the level of cortical PRmRNA of the 8-day-old
      rats were greater than the 2-day-old rats. These results indicate that the RT-PCR
      assay is useful for detection and quantification of PRmRNA in the neonatal rat
      cerebral cortex, and that increment of the cortical PRmRNA in the 8-day-old rat
      is associated with a drastic change of the level of the cortical PR around day
      10.

PMID- 1373303
TI  - Immunoreactive EGF in human benign prostatic hyperplasia: relationships with
      androgen and estrogen receptors.
AB  - Benign prostatic hyperplasia (BPH) is a sex steroid dependent disease. Estrogens
      and androgens can modulate in different mammalian tissues epidermal growth factor
      (EGF) production and/or secretion. In order to clarify the relationships between
      estrogen and androgen receptor concentrations and those of immunoreactive EGF
      (irEGF), we have evaluated these parameters in 14 human BPH samples, by means of
      a dextran-coated charcoal method and radioimmunoassay, respectively. Cytosolic
      steroid receptors did not seem to correlate with irEGF. A linear significative
      relationship was evident between nuclear androgen receptor (ARn) levels and
      endogenous irEGF but not between nuclear estrogen receptors and irEGF: in ARn
      negative BPH samples, irEGF levels were lower than in ARn positive ones.
      Therefore, it is possible that androgens act at prostatic tissue level, through
      their own receptors, by modulating EGF production and/or secretion.

PMID- 1373304
TI  - Partial purification of 3 alpha- and 3 beta-hydroxysteroid dehydrogenases from
      human hyperplastic prostate. Comparison between the two enzymes.
AB  - 3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) activity has been purified to
      homogeneity, the enzyme is a monomer with a Mw of 32,000 Da. 3 beta
      Hydroxysteroid dehydrogenase (3 beta-HSD) activity has been partially purified
      and has an apparent Mw of 30,000 Da. Both enzymes have the same cofactor
      requirements, optimal pH. However, 3 beta-HSD appeared to be an integral protein
      dependent on protein environment for its activity while 3 alpha-HSD activity is a
      protein more loosely associated to membranes.

PMID- 1373305
TI  - 17 beta-acylurea derivatives of 4-azasteroids as inhibitors of testosterone 5
      alpha-reductase.
AB  - A series of 17 beta-acylurea-4-aza-5 alpha-androstan-3-one derivatives has been
      assayed in vitro as inhibitors of testosterone 5 alpha-reductase, using the
      particulate fraction of human hyperplastic prostate and rat prostate as enzyme
      sources. The most active derivatives were 1-[4-methyl-3-oxo-4-aza-5 alpha
      androstane-17 beta-carbonyl]- 1,3-dicyclohexylurea (compound 1) and 1-[4-methyl-3
      oxo-4-aza-5 alpha-androstane-17 beta-carbonyl]- 1,3-diisopropylurea (compound 3)
      which demonstrated IC50 values of 41 and 55 nM for the human enzyme and of 83 and
      53 nM for the rat enzyme, respectively. Neither compound showed any relevant
      binding affinity to the rat prostate androgen receptor (IC50 of approximately 100
      and 84 microM). When given orally in immature castrated rats together with
      subcutaneous testosterone propionate (TP) for 7 consecutive days, compound 3
      (laboratory code FCE 26073), at 3 mg/kg/day, significantly decreased the ventral
      prostate growth promoting effect of TP by 40-50%, whereas compound 1 was
      ineffective up to the dose of 10 mg/kg/day.

PMID- 1373306
TI  - Influence of captopril on adrenal cytochrome P-450s and adrenodoxin expression in
      high potassium or low sodium intake.
AB  - To investigate the role of the renin-angiotensin system in steroidogenic enzyme
      expression, the angiotensin-I converting enzyme inhibitor captopril was
      administered in conjunction with high potassium (K+) or low (Na+) intake to rats
      for a 7-day period. Northern blot analysis of adrenocortical zona glomerulosa RNA
      revealed that sodium restriction markedly increased mRNA production of P-450scc
      (3.1-fold) and P-450(11 beta) (3.4-fold) as well as of the electron donor
      adrenodoxin (2.0-fold). Captopril combined to the low Na+ diet led to suppression
      of these effects and, as also seen with captopril alone, further diminished P
      450(11 beta) mRNA levels below controls. These responses were accompanied by
      parallel changes in respective protein levels of the enzymes as indicated by
      Western blot analyses. Captopril was also shown to inhibit the K(+)-stimulated
      levels of P-450(11 beta) mRNA (3.3-fold) and protein (1.4-fold) beneath control
      values (0.6- and 0.8-fold, respectively). On the other hand, increased P-450scc
      mRNA and protein levels by K+ loading were not affected by captopril treatment.
      No response was observed in any steroidogenic enzyme expression in zona
      fasciculata-reticularis following either diet with or without captopril. Thus,
      the inhibitory effect of captopril on stimulated steroidogenesis seemed to be
      mediated in part through transcriptional regulation of P450s. In addition, it
      appeared that P-450(11 beta) expression might be under the control of the renin
      angiotensin system in both high K+ and low Na+ diets as opposed to the K+
      stimulation of P-450scc where other mechanisms seemed to be involved.

PMID- 1373307
TI  - The differential regulation of aldosterone output in hamster adrenal by
      angiotensinII and adrenocorticotropin.
AB  - Aldosterone was isolated from hamster adrenal cells and was identified by high
      performance liquid chromatography and thermospray mass spectroscopy analysis.
      Basal outputs from adrenal cell suspensions were of the same order of magnitude,
      8.4 +/- 1.9 ng and 8.0 +/- 0.7 ng/2 h/50,000 cells, for aldosterone and
      corticosteroid, respectively. The outputs of aldosterone and corticosteroid
      increased with K+ concentrations to reach maxima of 3.3- and 1.6-fold at 10 meq/l
      of K+. AngiotensinII (AII) produced dose-dependent increases in aldosterone and
      corticosteroid outputs with maxima of 3- and 4-fold, respectively. In contrast,
      ACTH induced relatively no changes in aldosterone output, whereas dose-dependent
      increases in corticosteroid output were found. In time study experiments, with
      10(-8) M AII, aldosterone and corticosteroid outputs were maximally increased
      after 1 h (6-fold) and 3 h (1.8-fold), respectively. At 10(-8) M, ACTH had a
      small stimulatory effect on aldosterone output after 6 h, whereas it provoked a
      gradual increase in corticosteroid output (up to 7-fold after 8 h of incubation).
      The effects of AII and ACTH on adrenal cytochrome P-450(11 beta) involved in the
      last steps of aldosterone formation were evaluated by combined in vivo and in
      vitro experiments. The P-450(11 beta) mRNA level was increased by a low sodium
      intake but not by a 24 h ACTH stimulus. These results taken together indicate
      that ACTH and AII differentially regulate P-450(11 beta). It is postulated that
      these two regulatory peptides regulate the hamster adrenal steroidogenesis by
      different P-450 genes.

PMID- 1373308
TI  - Electrophysiological recordings in solitary photoreceptors from the retina of
      squid, Loligo pealei.
AB  - A protocol was developed to isolate enzymatically photoreceptors from the retina
      of the squid, Loligo pealei. The procedure routinely results in a high yield of
      intact cells. Examination of solitary photoreceptors under Nomarski optics
      revealed that the fine morphological features described in anatomical studies of
      retinal sections are retained. The distal segment is up to 250 microns long, 4-7
      microns wide, covered in part by short microvilli; the inner segment and the cell
      body, with the initial portion of the axon, are also clearly discernible in
      solitary cells. Suction electrode measurements performed from the cell body
      confirmed that responsiveness to light survived cell isolation. Macroscopic
      membrane currents were measured using the whole-cell tight-seal technique, and
      the perforated-patch method. Step depolarizations of membrane voltage
      administered in the dark elicited a slowly activating, sustained outward current.
      Light stimulation evoked an inward current graded with stimulus intensity; the
      peak current could amply exceed 1000 pA. Intense photostimulation gave rise to a
      prolonged inward aftercurrent that lasted for tens of seconds. On-cell patch
      recording along the intermediate segment and most of the smooth areas of the
      distal segment showed a large incidence of silent patches, with the occasional
      presence of voltage-dependent channels. On the other hand, channel activity could
      be recorded more frequently from electrode placements near the apical tip of the
      cell, where the presence of microvilli could be confirmed visually. Some patches
      were unresponsive to voltage stimulation applied in the dark but produced
      distinct bursts of channel openings after illumination. The feasibility of single
      cell electrophysiology in isolated photoreceptors, together with the growing body
      of biochemical information on cephalopod preparations, makes squid an attractive
      model system to investigate the visual process in invertebrates using multiple
      experimental approaches.

PMID- 1373309
TI  - The 11q23 breakpoint in acute leukemia with t(11;19)(q23;p13) is distal to those
      of t(4;11), t(6;11) and t(9;11).
AB  - Thirteen cosmid probes were mapped on the long arm of chromosome 11 between 11q22
      and 11q24 by nonradioactive in situ hybridization. Starting with these
      localizations and those of other probes mapped to 11q23, four acute leukemias
      with translocations involving 11q23 were studied with the same method. The
      translocation breakpoints of the t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p21
      p22;q23), and t(11;19)(q23;p13) were confirmed to be distal to CD3D. The probe
      cC111-304 was proximal to the t(11;19) breakpoint while distal to the breakpoints
      of the other rearrangements. In view of the diversity of chromosomal
      abnormalities involving band 11q23, our finding extends the molecular
      heterogeneity of the breakpoint localization in leukemias with rearrangements
      involving 11q23.

PMID- 1373310
TI  - Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and
      17q in human breast carcinomas.
AB  - Fifty-nine primary breast carcinomas and 11 metastases were examined to identify
      genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and
      17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p
      (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours),
      13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59
      in 29%, and NM23HI in 26% of the primary tumours). Loss of all the markers except
      p144D6 was observed even more frequently in the metastases. Pairwise comparisons
      for concordance of allele losses on 17p indicated that there might be two genes
      on 17p implicated in breast cancer development; the TP53 gene and a gene located
      close to the p144D6 and pYNZ22.1 markers. LOH of the RBI gene was associated with
      LOH of pYNZ22.1 and p144D6, but not with LOH of TP53. LOH of RBI and TP53 was
      associated with occurrence of ductal carcinomas, RBI and p144D6 losses with
      tumour size, and p144D6 losses with positive node status as well. LOH of TP53 and
      the three 17q markers NM23HI, pTHH59, and pRMU3 was most frequently observed in
      tumours from postmenopausal women. p144D6 losses occurred most frequently in
      progesterone receptor-negative tumours, whereas pTHH59 losses occurred most
      frequently in oestrogen receptor-negative tumours. LOH of the investigated loci
      was not associated with ERBB2 protooncogene amplification, with positive family
      history of breast cancer, or with survival.

PMID- 1373311
TI  - Reciprocal translocation t(12;22)(q13;q13) in clear-cell sarcoma of tendons and
      aponeuroses.
AB  - Clear-cell sarcoma is a rare soft tissue sarcoma that displays certain
      similarities to malignant melanoma. In this paper we describe the karyotypic
      findings and in vitro growth characteristics of a short-term-cultured clear-cell
      sarcoma. The cultured tumor cells had preserved immunohistochemical
      characteristics and certain ultrastructural features of the primary tumour,
      including positivity for vimentin, S-100 protein, and a melanoma-associated
      antigen, supporting the authenticity of the cultured cells. Cytogenetic analysis
      revealed an abnormal stemline karyotype of 49,XY, -1, +8, +8, +12,
      +der(1)t(1;?)(p36.1-.3;?), t(12;22)(q13;q13). A similar or identical t(12;22) was
      recently reported in two of four clear-cell sarcomas. It is suggested that the
      t(12;22)(q13;q13) is a primary cytogenetic abnormality in clear-cell sarcoma and
      distinguishes this tumor type from malignant melanoma.

PMID- 1373312
TI  - Nonradioactive in situ hybridisation of the translocation t(1;7) in myeloid
      malignancies.
AB  - Bone marrow cells of four patients with t(1;7) and myelodysplasia or acute
      myeloid leukemia were analyzed using nonradioactive in situ hydridisation. As
      probes, centromeric alphoid DNA sequences of chromosomes 1 and 7, a satellite DNA
      probe for 1q12, and chromosome-specific libraries of chromosomes 1 and 7 were
      used. The breakpoints of the t(1;7)(p11;p11) as determined by banding analysis
      could be studied more accurately, and the recently proposed designation
      t(1;7)(cen;cen) was confirmed in all four cases. Colocalization of alphoid DNA
      sequences of chromosomes 1 and 7 by double target in situ hybridisation was
      demonstrated in metaphase cells and also in interphase nuclei. The in situ
      hybridisation method described is applicable for the screening of peripheral
      blood cells or archival material.

PMID- 1373313
TI  - Chromosomal in situ suppression hybridization of immunologically classified
      mitotic cells in hematologic malignancies.
AB  - Chromosomal in situ suppression (CISS) hybridization was performed with library
      DNA from sorted human chromosomes 8, 9, 15, 17, 21, and 22 on immunologically
      stained bone marrow cells of four patients with a hematologic neoplasm, including
      two patients with myelodysplastic syndrome and trisomy 8, one patient with
      promyelocytic leukemia bearing the translocation t(15;17)(q22;q11-12), and one
      patient with chronic myeloid leukemia and the translocation t(9;22)(q34;q11). In
      all patients, the results of conventional karyotype analysis could be confirmed
      by one- or two-color CISS hybridization using the appropriate chromosome-specific
      libraries. Our results show that CISS hybridization can detect both numerical and
      structural chromosome changes in immunologically classified cells with high
      specificity and reliability. The fact that chromosome spreads of very poor
      quality can now be included in such analyses is a decisive advantage of this
      approach. In addition, the suitability of this approach for interphase
      cytogenetics is discussed.

PMID- 1373314
TI  - Chromosomal abnormalities in skin following total body or total lymphoid
      irradiation.
AB  - Patients undergoing bone marrow transplantation often receive total body or total
      lymphoid irradiation as part of the conditioning regimen prior to marrow
      infusion. The cytogenetic effects of this therapy on skin fibroblasts were
      studied. Fibroblast cultures from eight skin biopsies were harvested in early
      passages for G-banded chromosome analysis. Four biopsies were from three patients
      who had high-dose cyclophosphamide and total body radiotherapy; one was from
      within and one was from outside the radiation field of a patient who had high
      dose cyclophosphamide and lymphoid radiotherapy, one was from a patient who had
      combination chemotherapy alone, and one was from a normal control. No abnormal
      mitoses were found in the control or the patient who had chemotherapy alone, and
      only two of 30 mitoses from skin outside the lymphoid radiotherapy field were
      abnormal. However, most cells (49-88%) from five biopsies within radiotherapy
      fields were abnormal. Typically, abnormal karyotypes were pseudodiploid and
      contained multiple balanced rearrangements, of which reciprocal translocations
      were most common. The data indicate that the radiotherapy used for bone marrow
      transplantation induces extensive, sustained chromosome abnormalities in vivo in
      skin fibroblasts.

PMID- 1373315
TI  - Cytogenetic abnormalities in an ossifying fibroma from a patient with bilateral
      retinoblastoma.
AB  - Cytogenetic analysis of a cemento-ossifying fibroma from a patient with
      nonfamilial bilateral multicentric retinoblastoma revealed three reciprocal
      translocations with the karyotype
      46,XY,t(1;18)(q21;q21.3),t(3;10)(p13;q22),t(6;11)(p22;p15). Routine and high
      resolution cytogenetic analysis of peripheral blood leukocytes showed an
      apparently normal, 46,XY chromosome pattern with no deletion of chromosome 13.
      Molecular analysis demonstrated no gross differences in the retinoblastoma gene
      or the TP53 gene between constitutional and tumor DNA. This is the first
      cytogenetic analysis of a cemento-ossifying fibroma and the first report of this
      tumor in a retinoblastoma patient. The data may be added to the small, but
      growing literature on cytogenetic aberrations in benign tumors and may lend
      insight into genes involved in cell proliferation and neoplastic transformation.

PMID- 1373316
TI  - t(11;18)(q21;q21) is a recurrent chromosome abnormality in small lymphocytic
      lymphoma.
AB  - We have identified two cases of previously untreated, small lymphocytic lymphoma
      with extranodal involvement, which had a reciprocal translocation,
      t(11;18)(q21;q21), as the sole cytogenetic abnormality. These two cases are
      remarkably similar to two previously reported cases carrying this translocation
      with regard to clinical features, cytogenetic abnormality, histologic subtype,
      and immunophenotype. Molecular genetic analysis of these two cases revealed
      clonal gene rearrangement of the IGH locus but only germline configuration of the
      BCL2 oncogene at 18q21 when probes and conditions that usually identify BCL2
      rearrangement in lymphomas were used. Lymphomas bearing an (11;18) rearrangement
      appear to make up a phenotypically identifiable subgroup. Identification of the
      genes at the translocation breakpoints will be important.

PMID- 1373317
TI  - Losses of 3p, 11p, and 13q in EJ/ras-transformable simian virus 40-immortalized
      human uroepithelial cells.
AB  - Five independent clones of Simian virus 40 (SV40)-immortalized human
      uroepithelial cells (CK/SV-HUC) were established after transfection of HUC
      cultures from the same tissue donor with plasmids encoding SV40 large T and small
      t antigen genes. Each CK/SV-HUC clone contained a unique SV40 integration site,
      and all expressed similar levels of SV40 mRNA. All five clones were
      nontumorigenic, but clones 2, 4, and 5 tumorigenically transformed after
      transfection at P19 with mutant EJ/ras and also spontaneously after 40 serial
      passages in vitro. In contrast, CK/SV-HUC clones 1 and 3 did not transform when
      either approach was used. These differences in transformability among CK/SV-HUC
      clones could not be predicted based on differences in SV40 gene expression nor on
      any in vitro growth property tested. In cytogenetic analyses, a transformable
      clone showed losses of three chromosome arms containing putative cancer
      suppressor gene regions, including 3p14----pter, 13q, and 11p, whereas the
      nontransformable clones showed none of these losses. Thus these data indicate
      that genetic losses on 3p, 11p, and 13q may contribute to tumorigenic
      transformation of SV40-immortalized human uroepithelial cells.

PMID- 1373318
TI  - Amplification of the topoisomerase II alpha gene in a non-small cell lung cancer
      cell line and characterisation of polymorphisms at the human topoisomerase II
      alpha and beta loci in normal tissue.
AB  - DNA was prepared from normal tissue and 19 lung cancer cell lines. Using probes
      which detect restriction fragment length polymorphisms at both the topoisomerase
      II alpha and beta loci, heterozygosity was detected at a frequency of 0.17 and
      0.37 for the alpha and beta loci, respectively. Southern blot analysis of DNA
      extracted from lung cancer cell lines detected amplification of both the
      topoisomerase II alpha and ERBB2 genes in the adenocarcinoma line Calu3. These
      results indicate that topoisomerase II alpha and ERBB2 may be closely linked on
      chromosome 17 and coamplified during adenocarcinoma progression. Since
      topoisomerase II is a target for several anticancer drugs, it will be of interest
      to study alterations to topoisomerase II genes during tumour development, as
      these may in part determine the response of the tumour to chemotherapy.

PMID- 1373319
TI  - Abnormalities of chromosomes 7 and 22 in human malignant pleural mesothelioma:
      correlation between Southern blot and cytogenetic analyses.
AB  - Southern blot hybridization studies were performed on 23 mesothelioma primary
      tumor specimens to detect chromosome 1-, 7-, and 22-specific numerical changes,
      gene amplifications, and gene rearrangements. The molecular findings were
      compared with previous cytogenetic findings. No gene rearrangements or
      amplifications were detected. A numerical abnormality of chromosome 7 was
      detected by Southern blot analysis in two cases in which no numerical abnormality
      had been detected by the previous chromosome study. A numerical aberration of
      chromosome 22 was detected in five cases, which was compatible with the
      cytogenetic finding of monosomy 22 in these cases. The Southern blot results for
      the copy numbers of chromosomes 7 and 22 were concordant with the cytogenetic
      findings in 65%-80% of the cases.

PMID- 1373320
TI  - t(11;18)(q21;q21.1): a recurring translocation in lymphomas of mucosa-associated
      lymphoid tissue (MALT)?
AB  - A distinct subtype of extranodal malignant lymphoma derived from mucosa
      associated lymphoid tissues (MALT) has recently been defined. We have detected an
      acquired t(11;18)(q21;q21.1) in a patient with a MALT lymphoma of the stomach.
      This translocation has previously been described in two other patients with
      extranodal lymphoma. The BCL2 oncogene, which is located at band 18q21.3 and is
      activated by the t(14;18)(q32;q21) in follicular lymphoma, was not rearranged in
      this case. This newly identified t(11;18) may be a recurring translocation
      specifically associated with MALT lymphomas. Genes located at the breakpoint
      sites of chromosome 11 and/or chromosome 18 may be crucial to the pathogenesis of
      this type of malignant lymphoma.

PMID- 1373321
TI  - Molecular cytogenetic analysis of a complex t(10;22;11) translocation in Ewing's
      sarcoma.
AB  - Fluorescence in situ hybridization (FISH) using chromosome-specific plasmid
      libraries and chromosome region-specific DNA markers allowed the characterization
      of a t(10;22;11) (p11.2;q12;q24) in a Ewing's sarcoma (ES). This study
      illustrates the usefulness of molecular cytogenetic analysis of ES, especially
      for determining the localization of the translocated 11q24-25 segment in complex
      or variant translocations.

PMID- 1373322
TI  - A synovial sarcoma with t(X;18)(p11;q11) in a patient with Turner's syndrome.
AB  - The first case of synovial sarcoma in a patient with Turner's syndrome (45,X) is
      reported. Cytogenetic analysis of the tumor cells showed that the only X
      chromosome was involved in the t(X;18)(p11;q11) characteristic of synovial
      sarcoma.

PMID- 1373323
TI  - Amide modes and protein conformation.

PMID- 1373324
TI  - Changes at the N-terminus of human brain creatine kinase during a transition
      between inactive folding intermediate and active enzyme.
AB  - CK-STAR, a monoclonal antibody against human brain creatine kinase (CK), can be
      shown by chemical cleavage mapping and peptide synthesis to recognize an epitope
      at the free N-terminus of the enzyme. The epitope could be largely reproduced by
      a synthetic peptide based on the first 18 amino acids and could be partly formed
      by the first 11 amino acids. The antibody did not bind to native CK, but it did
      bind to CK in various partially denatured forms and to an enzymically inactive
      intermediate in the refolding process. Competitive binding studies have shown
      that the N-terminal conformations of both the refolding intermediate and the free
      peptide resemble that of CK partially denatured by attachment to plastic. The
      results suggest that the final stages of CK refolding and reactivation involve a
      structural change at the N-terminus or its interaction with some other part of
      the CK molecule, thus masking the CK-STAR epitope.

PMID- 1373325
TI  - Human alpha 2-HS-glycoprotein/bovine fetuin homologue in mice: identification and
      developmental regulation of the gene.
AB  - Human alpha 2-HS-glycoprotein (AHSG) is a plasma protein synthesized in liver and
      selectively concentrated in bone matrix. It has been reported to be involved in
      bone formation and resorption as well as immune responses. Recently, AHSG was
      found to be the species equivalent protein of fetuin, the major fetal serum
      protein in cattle and sheep. The function and regulation of AHSG/fetuin in
      different species are not understood. We have isolated a liver cDNA clone that
      encodes the human AHSG/bovine fetuin homologue in the mouse. The AHSG/fetuin gene
      may have a role in differentiation since it is expressed in mouse limb buds and
      brain only at certain stages during development. Mouse liver AHSG/fetuin mRNA was
      present at low level at 12 days gestation but its level increased during the late
      part of gestation and peaked between 1 to 3 months after birth. The regulation of
      mouse AHSG/fetuin synthesis during development was found to be significantly
      different from that of sheep and bovine fetuin. Compared to fetuin, which is
      reduced in adult to 1 to 2% of the fetal level, mouse AHSG synthesis subsides
      only 50% 4 months after birth.

PMID- 1373326
TI  - spoVG sequence of Bacillus megaterium and Bacillus subtilis.
AB  - We have sequenced the stage V sporulation specific gene spoVG in both Bacillus
      megaterium and Bacillus subtilis. The open reading frames encode polypeptides of
      96 and 97 residues, respectively, and have an 88.6% amino acid identity. Both
      genes have putative rho-independent terminators. No significant amino acid or
      nucleotide homology of either gene was found when compared with sequences
      contained in either the Genbank or EMBL data bases.

PMID- 1373327
TI  - The control of mRNA stability in Escherichia coli: manipulation of the
      degradation pathway of the polycistronic atp mRNA.
AB  - The physical and functional stabilities of genes in the atp operon fall into two
      classes. The first two genes, atpI and atpB, are rapidly inactivated and degraded
      at the mRNA level. The remaining seven genes are more stable. In order to
      investigate how these stabilities are determined, DNA sequences encoding mRNA
      structures that influence degradative events in other systems, including RNAse
      III sites and REP sequences, were subcloned or synthesized and inserted into non
      coding regions of the operon. The effects of insertion of an RNAse III site
      depended on whether cleavage left an unstable 3' end or a stabilizing stem-loop
      upstream of the cutting point. Generation of an unstable 3' end destabilized the
      neighbouring upstream atp gene, thus modifying the course and rate control of
      degradation. Removal of the atp transcriptional terminator attenuated expression
      of the last gene of the operon, atpC. This effect was reversed by substitution of
      an alternative stem-loop for the terminator. REP sequences inserted into
      intercistronic regions apparently could not influence rate-controlling steps. The
      reported data shed light on the factors controlling the inactivation and
      degradation of genes in the polycistronic atp mRNA, and are discussed in relation
      to the general role of degradation processes in the control of gene expression.

PMID- 1373328
TI  - Alpha-fetoprotein expression in fetal kidney cells does not require enhancers.
AB  - Expression of the alpha-fetoprotein (AFP) and albumin genes was examined in fetal
      mouse kidney by analysis of tissue mRNA pool sizes during development and
      transient expression assays in primary kidney tissue culture cells. AFP is
      expressed at a much lower level in kidney than in liver but transcription of the
      gene is activated early during development and repressed after birth with a time
      course similar to liver. However, albumin mRNA was not detected in fetal or new
      born mouse kidney. Transient expression assays using AFP- and albumin-CAT
      (chloramphenicol acetyl transferase) vectors were employed to characterize cis
      acting elements active in the regulation of AFP expression in kidney. Primary
      fetal liver and kidney cells in culture were used for these assays. The AFP
      promoter is active in kidney cells and the information necessary for tissue
      specific expression and developmental repression are contained within the first
      1.0 kb of 5' flanking sequences of the AFP gene. In addition, the AFP upstream
      enhancer elements are inactive in primary kidney cells. The mouse albumin
      promoter is shown to be inactive in kidney cells. The results obtained using
      transient expression assays are consistent with the observed low level of AFP
      expression, developmental repression of AFP, and the absence of expression of
      albumin in the mouse kidney.

PMID- 1373329
TI  - Nucleotide sequences of serine tRNAs from Bacillus subtilis.
AB  - Three B. subitilis serine tRNAs were sequenced including modified nucleosides.
      All the serine tRNAs contained 1-methyl-adenosine in the D-loop. As other
      characteristic modified nucleosides, 5-methoxyuridine was found in the first
      letter of the anticodon in the tRNA(UGA).

PMID- 1373330
TI  - Mouse MRP8 and MRP14, two intracellular calcium-binding proteins associated with
      the development of the myeloid lineage.
AB  - MRP8 and MRP14 are two S100-like calcium-binding proteins of unknown function,
      associated with numbers of human inflammatory disorders. Both molecules have been
      described as L1 complex, cystic fibrosis antigen, or p8 and p14. We report here
      the cloning of mouse MRP8 and MRP14 and their pattern of expression during
      hematopoiesis. Mouse MRP8 and MRP14 proteins share 59% identity with their human
      counterparts, but they are more divergent than the other members of the S100
      protein family. Mouse MRP proteins are coexpressed in fetal myeloid progenitors,
      where they are detected as early as day 11 of gestation. In fetal liver and yolk
      sac, MRP+ cell populations increased in number, in association with the
      development of the myeloid lineage. In adult mouse, we identified MRP8 and MRP14
      proteins in immature myeloid cells of the bone marrow, myeloid cells in the
      splenic red pulp and marginal zone, in addition to monocytes and blood
      neutrophils. However, MRP expression is lost as cells terminally differentiate
      into tissue macrophages. In addition, using thioglycollate-induced peritoneal
      inflammatory exudates, we showed that MRP8 and MRP14 proteins are highly
      expressed in recruited neutrophils and monocytes.

PMID- 1373331
TI  - Inhibition of acute myelogenous leukemia blast proliferation by interleukin-1 (IL
      1) receptor antagonist and soluble IL-1 receptors.
AB  - Interleukin-1 (IL-1) has recently been reported to play an important role in
      acute myelogenous leukemia (AML) blast proliferation. We therefore investigated
      the effect of soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL
      1RA) on the growth of AML bone marrow blast progenitors from 25 patients. In the
      AML blast colony culture assay, sIL-1R and IL-1RA inhibited blast colony-forming
      cell replication in a dose-dependent fashion, at concentrations ranging from 10
      to 500 ng/mL (sIL-1R) and 10 to 1,000 ng/mL (IL-1RA), and their inhibitory effect
      was partially reversed by IL-1 beta. A similar inhibitory effect was also noted
      with the use of anti-IL-1 beta neutralizing antibodies. When AML blast
      progenitors were grown either in the presence of fetal calf serum (FCS) alone or
      with one of the following: phytohemagglutinin leukocyte-conditioned medium (PHA
      LCM), granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF,
      interleukin-3 (IL-3), or stem cell factor (SCF), addition of 100 ng/mL sIL-1R or
      IL-1RA inhibited blast colony formation by 3% to 96% and 2% to 97%, respectively.
      In sharp contrast, neither of these IL-1-inhibitory molecules significantly
      inhibited proliferation of normal marrow hematopoietic progenitors. Lysates of 2
      x 10(7) low-density AML marrow cells were tested for intrinsic IL-1 beta content
      using an enzyme-linked immunoadsorbant assay (ELISA). Samples from five of six
      patients showed high concentrations (ranging from 501 to 2,041 pg), whereas 2 x
      10(7) cells from two normal marrow aspirates yielded 54.6 pg of IL-1 beta. AML
      blast colony-forming cells from all six patients were inhibited by sIL-1R, IL
      1RA, or both. Incubation of nine samples of AML low-density cells with either sIL
      1R or IL-1RA reduced GM-CSF concentrations in cell lysates, and supernatants from
      nine (P less than .01) and six samples (P less than .037), respectively, and G
      CSF concentration in lysates from six of nine samples (P less than .03), and in
      supernatants from five of six samples (P less than .06) when studied by ELISAs.
      Our data implicate IL-1 in AML blast proliferation and suggest the potential
      benefits of using IL-1-inhibitory molecules in future therapies for AML.

PMID- 1373332
TI  - Multilineage phenotypes of interleukin-3-dependent progenitor cells.
AB  - Interleukin-3 (IL-3)-dependent murine FDCP-mix cells have multilineage
      differentiation capacity; they are nonleukemic, have a normal karyotype, and are
      nonimmortalized. These cells coexpress on their cell surface the "early" B
      lineage marker B220/CD45R and the myeloid marker Mac-1/iC3b receptor (CR3),
      transcribe germline T-cell receptor gamma genes, and express the macrophage
      lineage growth factor receptor gene c-fms as a predominant 8.4-kb transcript.
      They do not detectably express at the stable mRNA or protein level other lymphoid
      precursor cell genes including CD2, TdT, lambda 5, and BP1. Induction of
      granulocyte/macrophage differentiation in these cells closes down expression of
      the lymphoid genes and activates stable expression of genes specific to the
      myeloid lineage, including myeloperoxidase. Expression of the c-fms gene at the
      mRNA level is upregulated and the dominant stable transcript is now in the 4.1-kb
      form typical of the macrophage lineage. These data provide a plausible
      explanation for the coexpression of lymphoid and myeloid lineage markers on human
      leukemic cells of stem cell or progenitor cell origin and have implications for
      the programming of lineage potential in normal multipotential hematopoiteic
      progenitor cells.

PMID- 1373333
TI  - Effect of inflammatory cytokines on hypoxia-induced erythropoietin production.
AB  - The effects of the inflammatory cytokines interleukin-1 alpha (IL-1 alpha), IL-1
      beta, IL-6, transforming growth factor-beta (TGF-beta), and tumor necrosis factor
      alpha (TNF-alpha) on erythropoietin (Epo) production in Hep3B cells were
      examined. The addition of IL-1 alpha, IL-1 beta, or TNF-alpha resulted in a dose
      dependent inhibition of hypoxia-induced Epo production by as much as 89%. IL-1
      beta was the most effective cytokine tested, demonstrating half-maximal
      inhibition at 0.4 U/mL compared with 1.0 and 10.0 U/mL for IL-1 alpha and TNF
      alpha, respectively. TGF-beta also inhibited hypoxia-induced Epo production, but
      only by as much as 56%. In contrast to IL-1 alpha, IL-1 beta, TNF-alpha, and TGF
      beta, the addition of IL-6 to hypoxic Hep3B cells resulted in a dose-dependent
      stimulation of hypoxia-induced Epo production by as much as 81%. However, IL-6
      did not stimulate Epo synthesis in the absence of hypoxia, and was thus
      synergistic with hypoxia in inducing Epo production. Combinations of IL-1 alpha,
      TNF-alpha, and IL-6 were found to be additive in their effects on hypoxia-induced
      Epo production. By Northern blot analysis, Epo messenger RNA levels in Hep3B
      cells grown in 1% O2 were decreased when concurrently exposed to either IL-1
      alpha or TNF-alpha. The effects that IL-1 alpha, IL-1 beta, TGF-beta, TNF-alpha,
      and IL-6 have on hypoxia-induced Epo production may provide new insights into the
      signal transduction pathway by which hypoxia leads to changes in gene expression.
      In addition, the effects of these inflammatory cytokines on hypoxia-induced Epo
      production in vitro suggest that in various inflammatory disorders these
      cytokines may affect Epo production in vivo and may play a significant role in
      the pathogenesis of the anemia of chronic disease.

PMID- 1373334
TI  - Expressed full-length von Willebrand factor containing missense mutations linked
      to type IIB von Willebrand disease shows enhanced binding to platelets.
AB  - von Willebrand disease (vWD) variant type IIB is an inherited bleeding disorder
      resulting from the spontaneous binding of defective von Willebrand factor (vWF)
      to platelets in vivo. To identify the molecular basis for type IIB vWD, we used
      reverse transcription and the polymerase chain reaction to examine the nucleotide
      sequence of the platelet glycoprotein (GP) Ib-binding domain encoded by the vWF
      messenger RNA in an affected family, and in an unrelated affected individual. We
      identified two different missense mutations linked with expression of type IIB
      vWD. These mutations, which lead to Pro574----Leu and Val553----Met
      substitutions, respectively, were each introduced into the full-length vWF
      expression vector pvW198, and both wild-type (wt) and mutant vWF were transiently
      expressed in COS-7 cells. Binding assays showed that both mutant proteins showed
      significant non-ristocetin-dependent spontaneous binding to platelets, and that
      complete binding was induced by low concentrations of ristocetin that failed to
      induce platelet binding by wt vWF. The vWF/platelet interaction was inhibited by
      the anti-vWF monoclonal antibody (MoAb) AvW3, and the anti-GPIb MoAb AP1, which
      both block vWF binding to platelets. These results show that the identified
      missense mutations are the likely basis for the expression of type IIB vWD in
      these affected individuals.

PMID- 1373335
TI  - The SCF and c-kit genes in Diamond-Blackfan anemia.

PMID- 1373336
TI  - Serum pancreatic enzyme assays in acute abdomen: a comparative prospective study.
AB  - Serum amylase, pancreatic isoamylase, lipase, trypsinogen and elastase-1 were
      measured in 100 consecutive patients who were emergency admissions to a surgical
      department, and in 27 selected patients with proven acute pancreatitis who served
      as controls. The final diagnoses in the 100 patients of the study group were:
      acute pancreatitis in eight patients, other digestive diseases in 87, and
      urogenital tract diseases in five. In the control group, pancreas-specific
      enzymes were abnormally high in all patients and amylase in 26 out of 27. In the
      study group, all enzymes were markedly high in all eight patients with acute
      pancreatitis. In the remaining 92 patients, serum amylase was abnormally high in
      seven, and at least one pancreatic enzyme was elevated in 16. These elevations
      were generally mild. The diagnostic efficiency, i.e., the percentage of patients
      correctly classified, was 96% for pancreatic isoamylase and lipase, 93% for
      amylase, 91% for elastase-1, and 84% for trypsinogen. We conclude that serum
      lipase turbidimetric assay is the most suitable test for emergency diagnosis of
      acute pancreatitis, because it is highly sensitive and specific and simply and
      quickly performed.

PMID- 1373337
TI  - Maximizing opacification during excretory urography: effect of low-osmolarity
      contrast media.
AB  - Because of improved patient tolerance and decreased risks of idiosyncratic
      reaction, low-osmolarity contrast media are increasingly used for excretory
      urography. However, physiologic differences among patients may affect the optimal
      time for acquiring diagnostic radiographs during the pyelographic phase of the
      examination. A prospective, randomized, physician-blinded comparative study of 60
      adult patients was undertaken to determine if the time to peak opacification of
      the pyelocaliceal systems differs with different doses of nonionic and ionic
      contrast media. Three doses of contrast media were used: a high dose (based on
      body weight) of a high-osmolarity ionic contrast medium, a high dose (based on
      body weight) of a low-osmolarity non-ionic contrast medium and a lower, fixed
      dose of a low-osmolarity nonionic contrast medium. The diagnostic quality of the
      radiographs did not differ statistically with the dose or the contrast medium.
      However, acquiring an additional radiograph during abdominal compression greatly
      increased the chance of obtaining at least one radiograph with maximal diagnostic
      information during the pyelographic phase. Despite potential differences among
      contrast media in the degree of pyelocaliceal opacification or distension and
      diuresis, it is not necessary to modify the timing of film acquisitions during
      excretory urography when lower doses of low-osmolarity agents are administered.

PMID- 1373338
TI  - Is cerebral arteritis the cause of the Landau-Kleffner syndrome? Four cases in
      childhood with angiographic study.
AB  - Four children with Landau-Kleffner syndrome were studied over a six year period.
      They presented with acquired aphasia, epilepsy, and focal or generalized EEG
      discharges which were exacerbated during sleep. In addition, cerebral angiography
      demonstrated isolated arteritis of some branches of the carotid arteries in all
      cases. Computed tomographic and magnetic resonance images were normal.
      Nicardipine in a dose of 1 to 2 mg/kg/day, added to conventional anticonvulsant
      drugs provided effective supplementary control of seizures, of paroxysmal EEG
      discharges, and of language and behavioural disturbances, even several years
      after the onset of the disorder and in patients whose response to other
      medications, including steroids, had been poor. Interruption of nicardipine
      administration was followed by relapse of the language disorder. Repeat
      angiography was performed in all four patients and showed recanalization of
      obstructed vessels in two cases. Focal cerebral vasculitis may be the
      pathogenesis of the Landau-Kleffner syndrome and calcium channel blockers such as
      nicardipine may be effective and specific therapy.

PMID- 1373339
TI  - Abnormal humoral immune response to mucosal antigenic stimulation in patients
      with lung cancer.
AB  - Previous studies have suggested an inverse relationship between atopy and cancer
      of mucosal surfaces. Atopy is classically assessed by detecting specific
      immunoglobulin E (IgE) antibodies against inhalant allergens. However, Platts
      Mills recently proposed that atopy is the ability of an organism to recognize and
      to respond to limited doses of allergens presented at the mucosal level by
      producing not only IgE, but also immunoglobulin A and immunoglobulin G (IgG)
      antibodies. The authors compared the prevalence of atopy in 103 patients with
      lung cancer (a model of mucosal cancer), 51 patients with chronic obstructive
      pulmonary disease matched for age, sex, and smoking habits with patients with
      lung cancer, and 102 healthy control subjects. The authors investigated whether
      the IgG response to antigens presented at the mucosal level, exacerbated in
      atopic subjects, might inversely be decreased in patients with lung cancer. Serum
      IgE antibodies against five common inhalant allergens (Dermatophagoides
      pteronyssinus [Der p1], Aspergillus fumigatus, grass pollen, and cat and dog
      danders) were detected through a radioallergosorbent test assay. Serum IgG
      antibodies against allergens naturally presented at the mucosal level
      (respiratory mucosa with Der p1 and digestive mucosa with betalactoglobulin [BLG]
      and soya proteins [SP]) were measured through a solid phase enzyme-linked
      immunosorbent assay test. Atopic status was assessed in 19 patients (18.4%) with
      lung cancer, 9 patients (17.6%) with chronic obstructive pulmonary disease
      (COPD), and 18 healthy control subjects (17.6%). Distributions of specific IgG
      levels were represented on frequency histograms after natural logarithmic
      transformation and showed reduced levels of anti-Der p1 and anti-BLG IgG in the
      cancer population compared with the control populations but similar levels of
      anti-SP IgG. Influence of sex, age, smoking habits, histologic type of cancer,
      and its extent could be excluded. The authors' results show no difference in the
      prevalence of atopy between the three groups. They document a selective, rather
      than general, defect in the immune response initiated at the mucosal level in
      patients with lung cancer, the most frequent mucosal cancer in man.

PMID- 1373340
TI  - Do histocompatibility antigens influence the risk of head and neck carcinoma?
AB  - Associations were sought between specific histocompatibility antigens (HLA) of
      the human major histocompatibility complex and the incidence of head and neck
      squamous cell carcinoma (SqCC). Seventy sequential patients with SqCC and 217
      control subjects from the same geographic region were typed for HLA-A, HLA-B, and
      HLA-DR loci. These results were compared. Multivariate statistical analysis using
      stepwise logistic regression revealed significant associations between the
      incidence of SqCC and HLA-B14, HLA-DR3, and HLA-DR4 as well as smoking and the
      sex-smoking interaction. The authors concluded that certain host factors,
      including genetic constitution, and behavioral characteristics (i.e., smoking) as
      well as tumor biology, can influence the development of SqCC. The mechanism(s) of
      these associations may involve as yet undefined relationships between HLA region
      genes and the immune response.

PMID- 1373341
TI  - Altered glycosylation of alpha-fetoprotein in hepadnavirus-induced hepatocellular
      carcinoma of the woodchuck.
AB  - Altered glycosylation of alpha-fetoprotein (AFP) has been proposed as a marker of
      hepatocellular carcinoma (HCC) in humans. The lectin-binding properties of
      woodchuck AFP were investigated to determine if woodchuck hepatitis virus (WHV)
      induced HCCs are also accompanied by changes in AFP glycosylation. Ninety-eight
      to 100% of the AFP from normal, WHV-free woodchucks with physiologic AFP
      elevations and from WHV-carrier woodchucks with HCC bound to concanavalin A,
      indicating that virtually all of the AFP was glycosylated. Three percent or less
      of the serum AFP of normal woodchucks bound to Lens culinaris agglutinin (LCA).
      In contrast, the AFP from woodchucks with HCC had an increased LCA-binding
      fraction (range, 8-77%). The increased LCA-binding AFP in WHV-induced HCC is
      analogous to that which frequently accompanies hepatitis B virus (HBV)-induced
      HCC in humans. This study corroborates the relationship of altered glycoconjugate
      synthesis to virus-induced malignant transformation, confirms the importance of
      AFP glycoforms as markers of HCC, and demonstrates that the WHV-infected
      woodchuck should be useful in investigating changes in AFP glycosylation during
      hepadnavirus hepatocarcinogenesis and HCC growth.

PMID- 1373342
TI  - Anti-(human LFA-1) monoclonal antibodies bind P815 murine tumour cells.
AB  - Using anti-CD11a and anti-CD18 monoclonal antibodies (mAbs) directed respectively
      against the alpha and the beta chains of LFA-1, we obtained an important and
      specific staining of P815 murine tumour cells. Both ascitic and cultured cells
      displayed a positive staining. Other murine tumours of haematopoietic origin, as
      well as lymphocytes or lymphoblasts from DBA/2 mice, were not labelled by the
      same monoclonal antibodies. These results were surprising since, to our
      knowledge, no case of cross-reaction between species has been reported with LFA
      1. Moreover, competition assays showed that epitopes recognized by the two anti
      CD11a antibodies were different from those identified by H35.89.9, a mAb raised
      against the murine LFA-1 alpha chain. Using allogeneic cytotoxic T lymphocytes,
      we also showed that anti-(human LFA-1) mAbs were unable to block the lysis of
      P815 by these effector cells. Thus, the putative functional properties of these
      structures, as well as their importance from an antigeneic point of view, remain
      to be assessed.

PMID- 1373343
TI  - Cytotoxic T cell lines recognize autologous and allogeneic melanomas with shared
      or cross-reactive HLA-A.
AB  - Cytotoxic T lymphocytes (CTL), CD3+, alpha/beta T-cell-receptor-positive, are
      important effector cells with specific immunity in melanoma patients. The
      establishment and expansion in vitro of CTL of a specific phenotype to tumor
      cells strongly depends on the method of activation and sensitization with tumor
      cells. We generated CD3+ CTL lines to melanoma by co-culturing peripheral blood
      lymphocytes with autologous irradiated melanoma cells and repetitive stimulation
      with high-dose interleukin-4 in a "cocktail" culture medium. CTL lines were
      investigated for their specificity to kill autologous and allogeneic melanoma.
      Histocompatibility locus antigen (HLA) class I (A, B) molecules are important
      restrictive recognition antigens for CTL. Although these antigens are highly
      polymorphic, they can share a similar immunogenic molecular epitope(s) and can be
      immunologically cross-reactive. The CTL lines generated were found to kill not
      only autologous melanoma, but also allogeneic melanomas having class I HLA-A
      antigens shared or "cross-reactive" with autologous HLA-A. These CTL lines were
      poor killers of melanomas bearing non-shared or non-cross-reactive HLA-A. Cold
      target inhibition assays demonstrated this CTL cross-reactivity to allogeneic
      melanoma specificity. Epstein-Barr-virus-transformed autologous and allogeneic B
      lymphoblastoid cell lines failed to block autologous melanoma killing, indicating
      that CTL were not recognizing major histocompatibility complex antigens, serum
      proteins or culture medium products as the primary target antigen. HLA-A2 was the
      major shared HLA-A antigen recognized by CTL lines on the melanoma lines studied.
      CTL lines also recognized shared HLA-A11 and A24 on allogeneic melanoma. There
      were no CTL lines showing restriction to HLA-B. These results suggest that common
      tumor-associated antigens are present on melanomas and are recognized in
      association with distinct HLA-A epitopes by CTL.

PMID- 1373344
TI  - [Ervin Neher and Bert Sakmann, 1991 Nobel Prize laureates for physiology and
      medicine. Ion channels and the patch clamp technic].
AB  - E. Neher and B. Sakmann were awarded the Nobel Prize for achievements in
      Physiology or Medicine in 1991. They developed the "patch clamp technique" which
      enables measurement of ionic currents through channels in the plasma membrane of
      living cells, and characterized their functional properties. An overview of three
      types of ion channels is presented: voltage gated channels, ligand gated channels
      and G-protein gated channels. An attempt was made to correlate their function
      with the structure of the protein complexes that represent ionic channels. The
      perforated patch clamp technique is mentioned as an alternative that enables
      recording of membrane currents without washing out the content of the interior of
      the cells.

PMID- 1373345
TI  - The search for laboratory measures of outcome in rheumatoid arthritis.
AB  - A large number of laboratory tests have been developed within the past decade to
      measure factors involved in the immune inflammation of RA. These can be divided
      into genetic markers, general measures of inflammation, autoantibodies and tissue
      specific markers. In general, it is simpler to prove the power of a certain test
      to measure the disease process than to predict outcome. Apart from RF positivity
      and CRP/ESR, few, if any, tests have proven to be of importance in independent
      studies from different centres. Among the promising candidates for future work
      are detailed analysis of the HLA-D region genes, sulphoxidation status, the
      autoantibody against RA33 nuclear antigen, soluble IL-2 receptor measuring
      lymphocyte activity, hyaluronate/hyaluronan or PIIINP from synovial tissue, the
      combined use of COMP and proteoglycan epitope tests for cartilage matrix, and
      pyrodinoline cross-linking for collagen from bone and cartilage. The ideal
      setting for testing such markers are prospective cohort studies starting early in
      the disease, and since many such studies have been initiated recently, one can
      expect much new information in coming years. Attention needs to be devoted to the
      kinetics of marker metabolism, since many are degraded or removed at very fast
      rates from the circulation, making serum assays less informative.

PMID- 1373346
TI  - Natural and synthetic antifibrinolytics in cardiac surgery.
AB  - In an effort to reduce morbidity associated with transfusion of blood products,
      the use of antifibrinolytics to decrease bleeding and transfusions after
      cardiopulmonary bypass (CPB) is receiving widespread attention. The predominant
      haemostatic defect induced by CPB and, therefore, the mechanisms by which natural
      (aprotinin) or synthetic antifibrinolytics (sigma-amino-caproic acid, tranexamic
      acid) exert their effects have been difficult to define. Nonetheless, all three
      substances appear to be effective in the treatment or in the prevention of
      excessive bleeding associated with cardiac surgery. However, the administration
      of these drugs should not attempt to replace meticulous surgical and anaesthetic
      care. In particular, the importance of an appropriate transfusion practice cannot
      be overemphasized. The efficient use of these, sometimes expensive, drugs must
      take into account not only the initial cost, but also the short- and long-term
      economic consequences for the health care provider of using, or not using, a
      given medication. Unfortunately, the comprehensive data on which authoritative
      conclusions may be reached are not yet available. Pending availability of these
      data, the present use of antifibrinolytics at the Montreal Heart Institute is the
      following: (1) patients undergoing elective primary myocardial revascularization
      or valve surgery do not receive prophylactic antifibrinolytics; (2) patients
      undergoing repeat myocardial revascularization, repeat valve surgery, or primary
      or repeat combined procedures, receive prophylactic sigma-aminocaproic acid; (3)
      sigma-aminocaproic acid may be used to treat excessive chest drainage in the
      postoperative period; (4) the prophylactic and the therapeutic uses of low doses
      of aprotinin are currently under investigation.

PMID- 1373347
TI  - IGF binding protein 3 in patients with Laron type dwarfism: effect of exogenous
      rIGF-I.
AB  - OBJECTIVE: The aim of the study was to investigate the serum levels of IGFBP-3,
      the major IGF-I binding protein, in patients with Laron type dwarfism (LTD)
      before and after IGF-I treatment. DESIGN AND PATIENTS: Eight Laron type dwarfism
      patients (four children and four adults) were treated for 7 days by one daily
      s.c. injection of biosynthetic IGF-I in doses of 120 or 150 micrograms/kg/day.
      MEASUREMENTS: Blood was sampled in the fasting state before and 1 and 7 days
      after the last injection. RESULTS: It was found that IGF-I administration
      significantly reduced plasma hGH levels with recovery after one week of no
      treatment. Serum IGFBP-3 was abnormally low (0.70 +/- 0.37 mg/l) and decreased
      significantly further during IGF-I treatment (to 0.48 +/- 0.28 mg/l) (P less than
      0.065). CONCLUSIONS: The finding that serum IGFBP-3 is low in Laron type
      dwarfism, a disease due to molecular defects in the GH receptor, is compatible
      with the hypothesis that this IGF binding protein is GH-dependent. On the other
      hand the decrease during IGF-I administration and concomitant suppression of GH
      secretion may denote either that GH activity is not completely blocked in this
      syndrome or that there are additional mechanisms regulating IGFBP-3 synthesis.

PMID- 1373348
TI  - Repertoire of CD5+ and CD5- cord blood B cells: specificity and expression of VH
      I and VH III associated idiotopes.
AB  - Epstein-Barr (EBV)-immortalized B cell clones were established from CD5+ and CD5-
      cord blood B cells separated by flow cytometry. We have previously shown that IgM
      from many of the clones was polyreactive, exhibiting reactivity with a number of
      autoantigens. In this study, IgM produced by the clones was analysed by MoAb for
      the expression of cross-reactive idiotypes (CRI) associated with rheumatoid
      factor paraproteins and from defined VH and V kappa subgroups of immunoglobulin
      heavy and light chains. IgM produced by clones established from CD5+ and CD5- B
      cells expressed the VH I associated idiotope G8. Furthermore, IgM produced by
      both sets of clones exhibited a similar frequency of VH III heavy chain subgroup
      expression, as determined by reactivity with staphylococcal protein A (SpA) and
      VH III-associated CRI expression (B6 and/or D12). In contrast, expression of the
      V kappa III-associated 17.109 CRI was significantly higher in IgM antibodies
      produced by clones established from CD5+ compared with the CD5- clones (32 versus
      5%: P less than 0.05). Analysis of the VH and VL subgroup expression by IgM
      produced by the CD5+ and CD5- cord blood clones, and their autoantigen reactivity
      profile did not reveal restriction or selection within CD5+ and CD5- populations.
      However, our data suggest that differences may exist in the expression of certain
      germ-line genes between CD5+ and CD5- cord blood B cells and might indicate an
      expansion of CD5+ B cells within the fetal environment.

PMID- 1373349
TI  - Expression of the 40 kD protein in DLD-1 colon cancer cells and the effect of
      cytokines.
AB  - We recently reported the presence of an organ-specific 40 kD colonic protein
      which acts as an autoantigen(s) in patients with ulcerative colitis. Using a
      specific monoclonal antibody directed against 40 kD protein (7E12H12, IgM
      isotype), in conjunction with immunocytochemistry and flow cytometry, we examined
      the presence of the 40 kD protein on human colon cancer cells, DLD-1, and also
      characterized the ability of cytokines, IFN-gamma and tumour necrosis factor, to
      modulate the expression of this protein on these tumour cells. The presence of
      the 40 kD protein was localized to the plasma membrane; less was present within
      the cytoplasm. Following exposure to IFN-gamma (10-1000 U/ml), DLD-1 colon tumour
      cells showed a dose- and time-dependent increase in 7E12H12 antibody associated
      immunofluorescence, with the maximum 7E12H12 antibody binding observed with 100
      U/ml IFN-gamma at 48 h. In contrast, tumour necrosis factor did not alter the
      levels of anti-40 kD antibody binding over that of control cells. Since IFN-gamma
      is also known to induce class II major histocompatibility antigens, we examined
      the possibility of cross-reactivity of HLA class II antigens and Mr 40 kD
      epitope. Neither pre-incubation of DLD-1 colon tumour cells with anti-HLA class
      II antibodies followed by 7E12H12 nor co-incubation of both antibodies altered
      the amount of 7E12H12 antibody binding. Using a direct ELISA, a highly enriched
      preparation of Mr 40 kD protein reactive to anti-40 kD antibody did not react
      with HLA class II antibodies. The present results suggest that 40 kD protein is
      present on DLD-1 human colon tumour cells and that although the 40 kD protein
      epitope expression is increased by the lymphocyte-derived cytokine, IFN-gamma,
      the epitope is separate and distinct from the class II HLA antigens. Further
      studies on the 40 KD protein may elucidate its autoantigenic role in the
      pathogenesis of inflammatory bowel disease.

PMID- 1373350
TI  - Bone marrow and peripheral blood natural killer cell activity in lymphomas. Its
      response to IL-2.
AB  - Natural killer (NK) cytotoxic activity was simultaneously investigated in bone
      marrow mononuclear cells (BMMC) and peripheral blood lymphocytes (PBL) from nine
      Hodgkin's disease (HD) and 15 non-Hodgkin lymphoma (NHL) untreated patients.
      Twenty-five PBL samples and seven bone marrow specimens from healthy individuals
      were also included as control group (C). NK cell activity was evaluated in basal
      condition and post-stimulation with human recombinant IL-2 (rIL-2). Data were
      expressed in K values (number of BMMC or PBL needed to lyse 50% of the target
      cells). In basal condition, both HD and NHL patients showed a NK cell activity
      comparable to the C group, both in BMMC (HD, K = 2.48 +/- 1.3; NHL, K = 3.8 +/-
      2.0; C, K = 3.2 +/- 0.7) and PBL (HD, K = 2.0 +/- 1.0; NHL, K = 2.3 +/- 1.0; C, K
      = 2.2 +/- 0.2). Stimulation with rIL-2 induced a significant and comparable
      enhancement of the NK activity in PBL from HD, NHL and C while the response to
      rIL-2 of the BMMC in most of the HD and NHL patients was significantly greater
      than the C group. Responder cells were characterized by negative selection with
      specific MoAb plus complement as a CD3-, CD16+, CD56+ cytotoxic cell and further
      confirmed by flow cytometry. We postulate that IL-2 activation of bone marrow NK
      cell precursors, in addition to enhancing the activity of circulating NK, may be
      of value for the therapeutic rationale of IL-2 in patients with lymphoma.

PMID- 1373351
TI  - Myelin antigen reactive T cells in cerebrovascular diseases.
AB  - T cell reactivities to the putative autoantigens myelin basic protein (MBP), MBP
      peptides with amino acid residues 110-128 and 148-165, and myelin proteolipid
      protein (PLP) were examined in patients with acute ischaemic cerebrovascular
      disease (CVD) and, for comparison, in patients with inflammatory neurological
      diseases and other neurological diseases. A quantitative measure of these T cell
      reactivities was obtained by assessing numbers of T cells among blood and
      cerebrospinal fluid (CSF) mononuclear cells that secreted IFN-gamma in response
      to antigen in vitro. Higher numbers of T cells reactive with each of these four
      antigens were detected in peripheral blood from patients with CVD compared with
      patients of the two control groups. Among blood cells from the CVD patients,
      their average number was 2.3-4.2/10(5) mononuclear cells. MBP reactive T cells
      were several-fold enriched in the CSF of CVD patients. The findings strongly
      suggest that brain damage in context with acute CVD leads to an in vivo expansion
      of myelin reactive T cells.

PMID- 1373352
TI  - CD4 lymphocyte subset abnormalities associated with impaired delayed cutaneous
      hypersensitivity reactions in patients with X-linked agammaglobulinaemia.
AB  - Circulating CD4 lymphocyte subset (CD45RA; CD45RO; CD29; Leu8) levels were
      determined in nine patients with X-linked agammaglobulinaemia (XLA), nine
      patients with common variable immunodeficiency (CVI) and in 18 age- and sex
      matched controls. CD4CD45RO and CD4CD29 cells were significantly lower (P less
      than 0.01) in the XLA patient group (CD45RO, 15.7 +/- 10.2%; CD4CD29, 32.1 +/-
      14.6%) compared with CVI patients (61.8 +/- 25.4%; 60.1 +/- 11.2%) and normal
      controls (43.7 +/- 22.3%, 54.5 +/- 22.0%). The levels of CD4CD45RA and CD4Leu8
      cells were not abnormal in the XLA patient group. No selective reduction in CD4
      subsets was observed in the CVI patient group. Delayed cutaneous hypersensitivity
      testing of five XLA and five CVI patients revealed a significantly reduced
      response to recall antigens in patients with XLA. This may relate to the
      deficiency of circulating memory T cells observed in these patients.

PMID- 1373353
TI  - LAM-1/Leu 8 antigen is expressed on portal, but not on lobular intrahepatic
      mononuclear cells in inflammatory liver disease.
AB  - The expression of the selectin receptor LAM-1/Leu 8 was analysed in normal and in
      inflamed liver tissue, and its expression on mononuclear inflammatory cells was
      correlated with their topographical distribution in various compartments of the
      inflamed liver, in order to obtain new insights on possible molecular mechanisms
      involved in the traffic of mononuclear inflammatory cells throughout the diseased
      hepatic parenchyma. In normal liver tissue, few scattered mononuclear cells in
      portal and lobular parenchyma corresponded to both CD4+ and CD8+, as well as to
      CD45RA+ (2H4+) naive and CD45RO+ (UCHL1+) memory T cells, and were LAM-1/Leu 8+.
      In acute and chronic inflamed liver biopsies, CD45RO+ (UCHL1+) CD4+ and CD8+
      memory T cells largely predominated in both portal and lobular parenchyma. The
      expression of LAM-1/Leu 8 antigen on these memory T cells varied according to
      their localization in the liver parenchyma, and it was not correlated with
      specific aetiological causes. In acute hepatitis, the vast majority of T
      lymphocytes were LAM-1/Leu 8-. In chronic active hepatitis, memory T cells in
      portal tracts expressed LAM-1/Leu 8, whereas virtually all intralobular T cells
      accumulating in areas of periportal and intralobular inflammation were LAM-1/Leu
      8-. In chronic persistent hepatitis, the LAM-1/Leu 8+ T cells largely
      predominated among the numerous mononuclear inflammatory cells within enlarged
      portal tracts, whereas LAM-1/Leu 8- T cells were restricted to areas of
      intralobular 'spotty' inflammation. Therefore, two phenotypical populations can
      be recognized among the memory T cells in inflamed liver tissue, according to
      their topographical localization: LAM-1/Leu 8+ T cells predominating in portal
      tracts, and LAM-1/Leu 8- T cells predominating in the lobular parenchyma. These
      data show that during their migration through the inflamed liver parenchyma,
      memory T lymphocytes undergo phenotypical changes (LAM-1/Leu 8 shedding)
      according to their localization in different liver compartments (portal tracts
      vs. lobular parenchyma), suggesting multiple cellular and molecular mechanisms
      involved in the regulation of the leucocyte traffic through inflamed liver
      tissue.

PMID- 1373355
TI  - Improved neurological outcome following early anatomical correction of
      transposition of the great arteries.
AB  - The incidence of neurological residuals following anatomical correction of
      transposition of the great arteries (d-TGA) has not been described so far.
      Clinical examination, EEG recordings, and computed tomography (CT) scans were
      carried out in a consecutive series of 38 children with d-TGA surviving anatomic
      corrective surgery. The patients were classified into one of three groups
      according to the type of operation: 15 patients after two-stage approach (TSA)
      (Stage 1: pulmonary artery banding+aortopulmonary shunt; Stage 2: anatomic
      correction); 12 patients with primary anatomic correction within the first 2
      weeks of life (early switch, ES); 11 patients with primary anatomic correction
      later in infancy (later switch, LS). In 26 patients (68%) we found no
      abnormalities on neurologic examination, CT scan, or EEG. Four patients suffered
      from spastic hemiplegia, 3 of these had cortical brain damage visible on CT scan,
      and 3 had focal epilepsy as well. In 2 otherwise clinical normal patients
      cortical infarction could be seen on a CT scan. Thus, in 5 cases (13% of 38
      patients) cerebral infarcts were diagnosed by CT scan. The cortical vascular
      infarction was seen in 4 patients after TSA and in 1 after LS. In 6 patients we
      found other neurological abnormalities. Early anatomic correction in patients
      with d-TGA reduces the risk of cortical vascular infarction.

PMID- 1373354
TI  - Imbalance of CD4+ lymphocyte subsets in patients with mixed connective tissue
      disease.
AB  - CD4+ (helper/inducer) T lymphocyte subsets were studied in the peripheral blood
      from patients with mixed connective tissue disease (MCTD) by double-labelling
      immunofluorescence. The proportion of CD4+CD45RA+ cells was higher (P less than
      0.01) when compared with controls, whereas CD4+CD29+ cells were markedly
      diminished (P less than 0.001). CD4+CD29+ cells were lower than in patients with
      progressive systemic sclerosis who were studied in parallel. Upon stimulation
      with phytohaemagglutinin, CD4+ cells from MCTD patients showed a strong
      reactivity to acquire the CD29+ phenotype. Expression of high levels of CD29 and
      other adhesion molecules might lead to facilitated localization of CD4+ cells to
      inflamed tissue. It is suggested that an increased responsiveness of CD4+ cells
      to activation signals in vivo and accumulation of CD4+CD29+ cells at tissue sites
      could result in depletion of this cell subset in the peripheral blood of patients
      with MCTD.

PMID- 1373356
TI  - Survey of pain management therapy provided for children with sickle cell disease.
AB  - A questionnaire was sent to principal investigators of NIH-sponsored clinical
      research in sickle cell disease. Twenty of 21 respondents indicated they used
      parenteral narcotic analgesics for pain episodes sufficiently severe to warrant
      hospitalization. Eleven used meperidine; seven, morphine; and one each,
      nalbuphine, hydromorphone, and acetaminophen with codeine. They gave the agents
      at frequent, regular intervals or by continuous infusion. A total of 41 of more
      than 3,500 patients required chronic transfusion for pain control. Complications
      included meperidine-associated convulsions reported by nine respondents and
      addiction by six. This information indicates that vigorous pain-control methods
      are used at institutions having a special interest in providing medical care for
      children with sickle cell disease.

PMID- 1373357
TI  - Histochemical changes in the midgut of two ixodid tick species Boophilus
      microplus and Rhipicephalus appendiculatus during digestion of the blood meal.
AB  - The changes in the midgut epithelia of two ixodid tick species, Boophilus
      microplus and Rhipicephalus appendiculatus, have been studied using several
      histochemical techniques. It was revealed that there is an accumulation of RNA at
      the time of tick attachment to the host and prior to the arrival of the blood
      meal, indicating that the midgut digest cell is furnished with the machinery
      characteristic of a synthetic cell. There appears to be a synchrony in the
      appearance of granules with peroxidase activity and the uptake of haemoglobin
      into the midgut digest cells. Alkaline phosphatase activity was observed in the
      midgut epithelia of all ticks except in a few of the long-starved ticks, and was
      concentrated in the apical plasma membrane regions of those digest cells involved
      in absorption and the intracellular digestion of haemoglobin. The presence of
      these enzymes suggests that the midgut digest cell is a multifunctional cell
      capable of both secretory and digestive activities. The colloidal material in the
      midgut lumen was found to result from the accretion of several products both
      secreted and excreted by the midgut epithelial cells and exhibited different
      staining reactions depending on which component dominated. The nature of the
      material suggests that in addition to its its digestive function it may serve as
      a sink to bind all the by-products of digestion and thereby facilitate their
      excretion.

PMID- 1373358
TI  - Detection of hepatitis C virus-specific antigens in semen from non-A, non-B
      hepatitis patients.
AB  - Semen samples from nine patients clinically diagnosed as having non-A, non-B
      hepatitis (NANBH) were tested by an ELISA using antibodies raised in rabbits
      against HCV-specific antigens. The semen from all nine patients had elevated
      levels of HCV-specific antigen in comparison to semen from five healthy donors.
      Semen from five of the nine patients had significant levels of the HCV-specific
      antigen. Seven of the eight serum samples from these patients were reactive with
      the standard C-100 HCV ELISA. Eight of these nine patients had serum reactive for
      HCV-specific antibodies in our ELISA using HCV-specific antigens. This more
      direct evidence for viral presence supports the earlier epidemiological data
      suggesting that HCV could be transmitted sexually.

PMID- 1373359
TI  - Protective effect of 16,16-dimethyl prostaglandin E2 on isolated rat hepatocytes
      against complement-mediated immune attack.
AB  - 16,16-Dimethyl prostaglandin E2 was examined for its ability to inhibit
      complement-mediated in vitro hepatocytolysis by an antigen-antibody reaction. In
      the presence of fresh rat serum as a source of complement, 5-min culture of
      isolated rat hepatocytes with a monoclonal antibody against a rat liver-specific
      membranous antigen resulted in a marked, significant elevation in lactate
      dehydrogenase leakage into the culture medium. However, with heat-inactivated rat
      serum, such a reaction did not occur, indicating that the hepatocytolysis induced
      by the antibody was attributable to the membrane damaging action of complement
      activated by an antigen-antibody reaction. Pretreatment of the hepatocyte with
      16,16-dimethyl prostaglandin E2 significantly suppressed the cytolytic reaction
      induced by the antibody in a concentration-dependent manner. These results show
      that 16,16-dimethyl prostaglandin E2 is capable of protecting isolated rat
      hepatocytes against the membrane-damaging insult of activated complement.

PMID- 1373360
TI  - Prospective controlled trial with antiestrogen drug tamoxifen in patients with
      unresectable hepatocellular carcinoma.
AB  - Clinical and experimental evidence indicates that estrogens are involved in the
      control of hepatocyte proliferation both in normal and in neoplastic conditions.
      Thirty-two cirrhotic patients with unresectable or otherwise untreatable
      hepatocellular carcinoma were allocated to receive either tamoxifen (30 mg/day)
      or no treatment. The patients in the two groups were matched for age, male/female
      ratio, Child-Pugh class, approximate tumor volume (US and CT scan), and etiology
      of the underlying cirrhosis. Survival of the tamoxifen-treated patients (life
      table, Wilcoxon-Breslow) was significantly prolonged (P = 0.0038), with 35% (vs
      0%) survival at 12 months. No difference was observed between males and females
      or between alcoholic and nonalcoholic cirrhosis. In 40% of tamoxifen-treated
      patients, the levels of alpha-fetoprotein declined. In conclusion, the
      antiestrogen tamoxifen appears to be effective in the palliative treatment of
      hepatocellular carcinoma. An initial decline in alpha-fetoprotein levels may
      represent an early favorable prognostic sign.

PMID- 1373361
TI  - Management of malignant hilar biliary obstruction by endoscopy. Results and
      prognostic factors.
AB  - Between January 1983 and December 1987, 103 patients who had hilar biliary
      obstruction (59 men, 44 women, median age 73 years) were referred to our
      institution. The causes of hilar biliary obstruction were carcinoma of the bile
      ducts (55), hepatic metastases or hepatocellular carcinoma (30), and carcinoma of
      the gallbladder (18). When endoscopic retrograde cholangiography was performed,
      the stricture was classified as type I in 28%, type II in 41%, and type III in
      31% of the patients. In 92 patients, we tried to insert endoscopically a 10, 11,
      or 12 F Amsterdam type prosthesis; it proved possible in 66 (74%), and the
      prosthesis proved functional without further procedure in 49 cases (53%); no
      combined percutaneous and endoscopic method was used. At death or discharge, 45
      patients (49%) had a successful drainage. Cholangitis was the main procedure
      related complication and occurred in 25 patients. The 30-day mortality was 43%.
      Results varied according to type of stenosis: successful drainage was performed
      in 15% of the patients with type III stenosis, compared with 86% when the
      stenosis was of type I. Under a multivariate analysis the independent prognostic
      factors of 30-day mortality were: (1) development of infectious complications
      after endoscopic attempt at drainage (P less than 0.0001), and (2) absence of
      successful drainage (P less than 0.0001). In conclusion, endoscopic
      endoprosthesis placement allows a sufficient drainage in 53% of the cases. In
      type III stenosis, the high rate of 30-day mortality leads us the conclusion that
      endoscopic drainage must be avoided.

PMID- 1373362
TI  - Reinforcement of subliminal flexion reflexes by transcranial magnetic stimulation
      of motor cortex in subjects with spinal cord injury.
AB  - A 20 msec train (500 Hz; 0.1-0.2 msec duration) of percutaneous electrical
      stimulation (ES) applied to the plantar surface was used to condition muscle
      responses evoked in tibialis anterior (TA) by transcranial magnetic stimulation
      of the motor cortex in 8 subjects with traumatic spinal cord injury (SCI). The
      intensity of conditioning ES was adjusted to just subthreshold for evoking
      flexion reflexes in TA and was delivered at conditioning-test (C-T) intervals of
      15-60 msec prior to cortical stimulation. Four subjects with clinically complete
      SCI revealed no muscle response to cortical stimulation or following combined
      subliminal percutaneous ES and cortical stimulation. Four subjects (3 clinically
      incomplete and 1 complete injury) demonstrated muscle responses with a latency of
      70-80 msec time-locked to the percutaneous ES when the conditioning subliminal
      stimulation was delivered at C-T: 15-40 msec. These responses, resembling
      suprathreshold flexion reflexes, reflect the convergence of excitatory afferent
      and cortical inputs and provide evidence of preserved corticospinal innervation
      to the L4-5 segmental motoneuron or interneuron pools. In 3 of the subjects this
      preserved corticospinal influence was evident despite absence of motor evoked
      potentials (MEPs) following cortical stimulation. The effect of the combined
      electrical and cortical stimulation in yielding suprathreshold flexion reflexes,
      instead of the facilitated MEPs seen in control subjects, appears to be related
      to slowed central conduction, prolonged temporal dispersion of the motoneuron
      facilitation following cortical stimulation and segmental reflex changes
      associated with disrupted modulation of interneuronal pathways. The results show
      this conditioning paradigm to be useful in revealing preserved corticospinal
      innervation in some SCI subjects with absent MEPs.

PMID- 1373363
TI  - Percutaneous magnetic stimulation of the motor cortex in migraine.
AB  - We have used transcranial magnetic stimulation of the motor cortex interictally
      in 12 patients with unilateral classic migraine with sensorimotor auras and 10
      patients with common migraine and unilateral headache. In classic migraine, the
      threshold of activation of the FDI muscle by the cortical stimulus was
      significantly increased on the side of the auras, when compared to the unaffected
      side (P less than 0.01) and to normal subjects (P less than 0.01). The amplitude
      of EMG responses was also reduced in FDI on the affected side when compared to
      normals (P less than 0.02). Responses obtained in common migraine patients were
      normal on both sides. We suggest that some permanent subclinical dysfunction of
      the motor cortex might play a role in the pathogenesis of attacks of classic
      migraine with sensorimotor auras.

PMID- 1373364
TI  - The heating of metal electrodes during rapid-rate magnetic stimulation: a
      possible safety hazard.
AB  - The temperature of electrodes and metal disks positioned close to a coil was
      measured during rapid-rate magnetic stimulation. The temperature rise ranged from
      a fraction of a degree to almost half a degree per stimulus pulse and increased
      with the electrical conductivity of the metal, the square of the electrode radius
      and the square of the stimulus strength, and was independent of the electrode
      thickness. During a brief high-frequency train, the temperature increase from
      each pulse added; during a long, high-frequency train the temperature increase
      approached a steady state. After the stimulus ended, an electrode on the arm
      cooled with a time constant of about 45 sec. A standard silver EEG electrode on
      the surface of the skin did not increase in temperature enough to induce a skin
      burn if the stimulating rate was below 0.4 Hz or the total number of stimuli was
      less than 20. Heating was reduced by cutting gaps in the electrode.

PMID- 1373365
TI  - Motor axon reflex and indirect double discharge: ephaptic transmission? A
      reappraisal.
AB  - Causal mechanisms of the motor axon reflex (MAR) and indirect double discharge
      (IDD) are re-examined. The hypothesis that these indirect intermediate latency
      responses result from an axono-axonal ephaptic transmission mechanism has
      recently been suggested. The various conceivable responses of models of axonal
      cross-talk are compared with actual observations made from the limbs. We conclude
      that the ephaptic hypothesis does not explain MAR and IDD, and that the earlier
      understanding that MAR results from axonal branching and IDD from proximal re
      excitation on the axon holds true.

PMID- 1373366
TI  - Relief of hemiparetic spasticity by TENS is associated with improvement in reflex
      and voluntary motor functions.
AB  - Our previous studies showed that a single 45 min application of transcutaneous
      electrical nerve stimulation (TENS) prolonged soleus H and stretch reflex
      latencies in hemiparetic subjects. In addition, 9 daily 30 min TENS applications
      enhanced vibratory inhibition of the H reflex and tended to decrease hyperactive
      stretch reflexes. These findings suggested that longer-term TENS may be effective
      in reducing hemiparetic spasticity. Our present objectives were 2-fold: to
      determine whether longer-term repetitive TENS stimulation would lead to a
      reduction in clinical spasticity in hemiparetic subjects, and whether such a
      reduction could be associated with a decrease in stretch reflex excitability and
      an improvement in voluntary motor function. We compared the effects of 15 daily
      60 min TENS treatments over a 3 week period, with those of placebo stimulation
      applied to the common peroneal nerve of the affected leg in similar groups of
      spastic hemiparetic subjects. Our test battery consisted of 5 measurements which
      assessed (1) clinical spasticity scores, (2) maximal H reflex to M response
      ratios, (3) vibratory inhibition of H reflex, (4) stretch reflexes, and (5)
      maximal voluntary isometric plantarflexion and dorsiflexion, in standing. In
      contrast to placebo stimulation which produced no significant effects, repeated
      applications of TENS over time decreased clinical spasticity (P less than 0.05),
      and increased vibratory inhibition of the soleus H reflex (P = 0.02) after 2
      weeks. These changes occurred with a substantial improvement in voluntary
      dorsiflexing force up to 820%, but not plantarflexing force. They were followed
      by a reduction in the magnitude of stretch reflexes (P = 0.05) in the spastic
      ankle plantarflexor, concomitant with a decrease in the EMG co-contraction ratios
      after a further week of stimulation. Our results thus indicated that repeated
      applications of TENS can reduce clinical spasticity and improve control of reflex
      and motor functions in hemiparetic subjects. Furthermore, the underlying
      mechanisms may be due partly to an enhancement in presynaptic inhibition of the
      spastic plantarflexor, and partly to a possible "disinhibition" of descending
      voluntary commands to the paretic dorsiflexor motoneurons.

PMID- 1373367
TI  - Diagnostic function of the microhuman prototype of the expert system--MUNIN.
AB  - This paper describes the diagnostic function of a prototype expert system for
      electromyography (EMG). The prototype was restricted to a limited "Microhuman"
      anatomy with only 6 muscles and 8 nerves, and a corresponding limitation on the
      number of local nerve lesions. It attempted to give a detailed description of the
      most important groups of generalized nerve and muscle disorders, and the commonly
      used parameters from needle EMG and nerve conduction studies were included. The
      system can be used both for "diagnostic" and for "causal" reasoning. In
      diagnostic reasoning, the system's probabilistic inference engine is used to
      reason from test results through 14 different aspects of neuromuscular
      pathophysiology to disorders. In causal reasoning, the system reasons in the
      opposite direction from disorders through pathophysiology to expected test
      results. The diagnostic function of the system was illustrated by 3 cases: a
      normal subject, a patient with a bilateral carpal tunnel syndrome and a patient
      with both a diabetic polyneuropathy and a bilateral carpal tunnel syndrome.

PMID- 1373368
TI  - Silent period measurement revives as a valuable diagnostic tool with transcranial
      magnetic stimulation.
AB  - Following magnetic transcranial stimulation (TCS) a post-excitatory pause can be
      observed in surface electromyographic (EMG) recordings from pre-innervated
      muscles. We studied the duration of this silent period (SP) in the abductor
      pollicis brevis muscle while varying the stimulus intensity (SI) and the amount
      of the voluntary tonic contraction in 23 normal adults aged 20-78 years. A
      multivariate linear regression analysis revealed a positive correlation of SP
      with SI and a slight negative correlation with age. In 11 hemiparetic patients a
      relative increase of the SP was found on the affected side despite normal central
      motor conduction time. A marked shortening of the SP in relation to controls was
      observed in 6 parkinsonian patients.

PMID- 1373369
TI  - The clinical usefulness of magnetic cortical stimulation.

PMID- 1373370
TI  - Magnetoelectrical stimulation of motor cortex in children with motor
      disturbances.
AB  - Transcranial magnetoelectrical stimulation (TMS) is now widely used as a
      diagnostic tool in adults. In this study we report our experiences with this
      technique in children with central motor disturbances. We used a Cadwell MES10
      magnetoelectrical stimulator with a maximal magnetic field of 2 tesla. The
      stimulation procedure followed a standardized protocol, with the patients being
      as relaxed as possible in order to avoid contamination of parameters with
      different preinnervational levels. Stimulation data were compared to a data base
      obtained in 58 normal children. The first group of patients consisted of 20
      children aged from 7 months to 16 years with hemiparesis of different etiologies.
      Neuroimaging data were correlated with the results of magnetoelectrical
      stimulation. In 13 patients a pathological pattern of TMS could be detected, and
      in 7 of these a corresponding lesion of the cortico-spinal tract was found in CT
      or MRI scans. In 7 children TMS was normal, in spite of a clear-cut lesion of the
      cortico-spinal tract in CT or MRI scans in 4 of them. The second group of
      patients consisted of 16 children with extrapyramidal disease, mostly of
      hereditary origin, such as DOPA-responsive dystonia or benign hereditary chorea.
      TMS showed a normal response pattern in this group. We discuss problems and
      possible pitfalls in TMS in childhood in evaluating the diagnostic value of TMS.
      At the moment the diagnostic usefulness of TMS in children with motor
      disturbances appears limited and calls for careful interpretation.

PMID- 1373371
TI  - Afferent conditioning of motor evoked potentials following transcranial magnetic
      stimulation of motor cortex in normal subjects.
AB  - The present study determined the effects of percutaneous electrical stimulation
      of the plantar surface on motor evoked potentials (MEPs) in tibialis anterior
      (TA) and soleus (SOL) of normal subjects following transcranial magnetic
      stimulation of motor cortex. The conditioning stimulation consisted of a 20 msec
      train of electrical pulses (500 Hz; 0.1 msec rectangular) delivered to the medial
      border of the sole of the foot at an intensity just subthreshold for evoking a
      flexion reflex. The conditioning (C) stimulation preceded the test (T) cortical
      stimulation by intervals of 20-130 msec. Magnetic stimulation of motor cortex
      (Cadwell MES-10) was delivered through a 9.5 cm focal point coil positioned
      tangential to the scalp and located with the rim over vertex. Five healthy adults
      served as subjects and each was investigated on at least 2 occasions. At C-T
      intervals 20-50 msec there was a mild inhibition of MEPs in both TA and SOL. This
      was followed by marked facilitation (greater than 300%) of MEPs at C-T intervals
      50-85 msec in both TA and SOL in all subjects. At longer C-T intervals greater
      than 110 msec, there was an inhibition of MEPs in TA but not in SOL. Based on the
      time course of these 3 phases of MEP amplitude modulation, and different
      stimulation thresholds for each phase, it appears that separate
      neurophysiological processes underlie each phase of MEP modulation. These
      observations also suggest that percutaneous electrical stimulation may be useful
      as a means of enhancing low amplitude or subliminal MEPs in normal subjects or
      patients with myelopathy.

PMID- 1373372
TI  - Selected CSF biochemistry and gabapentin concentrations in the CSF and plasma in
      patients with partial seizures after a single oral dose of gabapentin.
AB  - Gabapentin (GBP) is a neutral amino acid and a GABA analog which in animal
      experimental models has shown a broad anticonvulsant spectrum. To evaluate the
      penetration of GBP into the CSF in humans as well as its possible effects on free
      and total GABA, homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA),
      a special investigation was performed as part of a placebo controlled add-on
      study of GBP in partial epilepsy. At the end of the 3-month double-blind period,
      5 patients on placebo were given a single oral dose of GBP. Four patients
      received 600 mg and 1 patient 1200 mg GBP. CSF was collected immediately before
      and at 6, 24 and 72 h after the single dose. 5 ml of plasma was collected at 1,
      2, 3, 6, 12, 24, 48 and 72 h. Plasma concentrations and plasma elimination half
      life (4-6 h) of GBP were in agreement with the results of previous studies. The
      CSF/plasma concentration ratio of GBP 6 h after drug was 0.1. After 24 h, GBP
      could only be recovered in the CSF of the patient given 1200 mg. The CSF/plasma
      ratio at that time was 0.3. Free and total GABA concentrations did not change,
      but CSF 5-HIAA and HVA increased at 24 and 72 h post dose. The CSF/plasma ratio
      of gabapentin is similar to that of other amino acids.

PMID- 1373373
TI  - Inhibition of the ADP-glucose pyrophosphorylase in transgenic potatoes leads to
      sugar-storing tubers and influences tuber formation and expression of tuber
      storage protein genes.
AB  - Transgenic potato plants were created in which the expression of ADP-glucose
      pyrophosphorylase (AGPase) was inhibited by introducing a chimeric gene
      containing the coding region of one of the subunits of the AGPase linked in an
      antisense orientation to the CaMV 35S promoter. Partial inhibition of the AGPase
      enzyme was achieved in leaves and almost complete inhibition in tubers. This
      resulted in the abolition of starch formation in tubers, thus proving that AGPase
      has a unique role in starch biosynthesis in plants. Instead up to 30% of the dry
      weight of the transgenic potato tubers was represented by sucrose and up to 8% by
      glucose. The process of tuber formation also changed, resulting in significantly
      more tubers both per plant and per stolon. The accumulation of soluble sugars in
      tubers of antisense plants resulted in a significant increase of the total tuber
      fresh weight, but a decrease in dry weight of tubers. There was no significant
      change in the RNA levels of several other starch biosynthetic enzymes, but there
      was a great increase in the RNA level of the major sucrose synthesizing enzyme
      sucrose phosphate synthase. In addition, the inhibition of starch biosynthesis
      was accompanied by a massive reduction in the expression of the major storage
      protein species of potato tubers, supporting the idea that the expression of
      storage protein genes is in some way connected to carbohydrate formation in sink
      storage tissues.

PMID- 1373374
TI  - Heterodimerization between light-regulated and ubiquitously expressed Arabidopsis
      GBF bZIP proteins.
AB  - The promoters of a variety of plant genes are characterized by the presence of a
      G-box (CCACGTGG) or closely related DNA motifs. These genes often exhibit quite
      diverse expression characteristics and in many cases the G-box sequence has been
      demonstrated to be essential for expression. The G-box of the Arabidopsis rbcS-1A
      gene is bound by a protein, GBF, identified in plant nuclear extracts. Here we
      report the isolation of three Arabidopsis thaliana cDNA clones encoding GBF
      proteins referred to as GBF1, GBF2 and GBF3. GBF1 and GBF2 mRNA is present in
      light and dark grown leaves as well as in roots. In contrast, GBF3 mRNA is found
      mainly in dark grown leaves and in roots. The deduced amino acid sequences of the
      three cDNAs indicate that each encodes a basic/leucine zipper protein. In
      addition, all three proteins are characterized by an N-terminal proline-rich
      domain. Homodimers of the three proteins specifically recognize the G-box motif,
      with GBF1 and GBF3 binding symmetrically to this palindromic sequence. In
      contrast, GBF2 binds to the symmetrical G-box sequence in such a way that the
      juxtaposition of the protein and the DNA element is clearly asymmetric and hence
      distinct from that observed for the other two proteins. The fact that GBF1, GBF2
      and GBF3 possess both distinct DNA binding properties and expression
      characteristics prompt us to entertain the notion that these proteins may
      individually mediate distinct subclasses of expression properties assigned to the
      G-box. Furthermore, we demonstrate that GBF1, GBF2 and GBF3 heterodimerize and
      these heterodimers also interact with the G-box, suggesting a potential mechanism
      for generating additional diversity from these GBF proteins.

PMID- 1373375
TI  - Insect immunity: developmental and inducible activity of the Drosophila
      diptericin promoter.
AB  - Diptericins are 9 kDa inducible antibacterial peptides initially isolated from
      immune haemolymph of Phormia (Diptera). Following the isolation of a Drosophila
      cDNA encoding a diptericin homologue, we have now cloned a genomic fragment
      containing the Drosophila diptericin gene. To dissect the regulation of this
      gene, we have transformed flies with a fusion gene in which the reporter beta
      galactosidase gene is under the control of 2.2 kb upstream sequences of the
      diptericin gene. We show that such a fusion gene is inducible by injection of
      live bacteria or complete Freund's adjuvant and respects the tissue specific
      expression pattern of the resident diptericin gene. Our analysis reveals at least
      four distinct phases in the regulation of this gene: young larvae, late third
      instar larvae, pupae and adults. This complexity may be related to the presence
      in the upstream sequences of multiple copies of response elements previously
      characterized in genes encoding acute phase response proteins in mammals (e.g. NK
      kappa B, NF-kappa B related, NF-IL6 response elements).

PMID- 1373376
TI  - Regulation of polyadenylation in human immunodeficiency virus (HIV):
      contributions of promoter proximity and upstream sequences.
AB  - Retroviruses synthesize a terminally redundant genomic RNA that contains
      canonical polyadenylation signals at both ends. Production of this RNA requires
      that the 5' copy of these signals be ignored, while the 3' copy must be utilized.
      Two models have been presented for how this occurs in the human immunodeficiency
      virus, HIV: (i) the core HIV poly(A) signals (AAUAAA and a downstream GU-rich
      element) might be inefficient and require supplementation by activating sequences
      found only at the 3' end of the RNA; or (ii) cap site proximity might actively
      suppress polyadenylation at the 5' site. We have examined both possibilities in
      HIV-infected cells and in cells transfected with a variety of model constructs.
      We find that infected cells harbor few or no detectable products of 5'
      polyadenylation; however, the core HIV processing signals can mediate processing
      fairly efficiently (65%) when positioned at the 3' end of heterologous
      transcripts. While this efficiency can be further increased to greater than 95%
      by inclusion of upstream sequences from the viral U3 region, the absence of these
      U3 signals is insufficient by itself to account for 5' signal bypass. By
      contrast, the efficiency of these core elements is greatly suppressed when they
      are positioned within approximately 450 nucleotides of the cap site. This
      distance-related suppression can be modestly diminished by insertion of U3
      sequences between the cap site and HIV poly(A) signal. We suggest that the
      primary determinant of 5' poly(A) site bypass is cap site proximity; the absence
      of U3 sequences at this position contributes secondarily to the bypass by
      enhancing the sensitivity of the pA signal to the suppressive effects of promoter
      proximity.

PMID- 1373377
TI  - Expression of a chimeric ribozyme gene results in endonucleolytic cleavage of
      target mRNA and a concomitant reduction of gene expression in vivo.
AB  - The subclass of catalytic RNAs termed ribozymes cleave specific target RNA
      sequences in vitro. Only circumstantial evidence supports the idea that ribozymes
      may also act in vivo. In this study, ribozymes with a hammerhead motif directed
      against a target sequence within the mRNA of the neomycin phosphotransferase gene
      (npt) were embedded into a functional chimeric gene. Two genes, one containing
      the ribozyme and the other producing the target, were cotransfected into plant
      protoplasts. Following in vivo expression, a predefined cleavage product of the
      target mRNA was detected by ribonuclease protection. Expression of both the
      ribozyme gene and the target gene was driven by the CaMV 35S promoter.
      Concomitant with the endonucleolytic cleavage of the target mRNA, a complete
      reduction of NPT activity was observed. An A to G substitution within the
      ribozyme domain completely inactivates ribozyme-mediated hydrolysis but still
      shows a reduction in NPT activity, albeit less pronounced. Therefore, the
      reduction of NPT activity produced by the active ribozyme is best explained by
      both hydrolytic cleavage and an antisense effect. However, the mutant ribozyme-
      target complex was more stable than the wildtype ribozyme--target complex. This
      may result in an overestimation of the antisense effect contributing to the
      overall reduction of gene expression.

PMID- 1373378
TI  - Overexpression of GRP78 mitigates stress induction of glucose regulated proteins
      and blocks secretion of selective proteins in Chinese hamster ovary cells.
AB  - GRP78 is a resident protein of the endoplasmic reticulum (ER) and a member of the
      glucose regulated protein (GRP) family. Many secretion incompetent proteins are
      found in stable association with GRP78 and are retained in the ER. Some proteins
      which are destined for secretion transiently associate with GRP78. To further
      increase our understanding of the role of GRP78 in secretion, we have stably
      overexpressed GRP78 in Chinese hamster ovary (CHO) cells and examined the effect
      on protein secretion and the stress response. GRP78 overexpressing cells treated
      with tunicamycin or A23187 exhibited a reduced induction of endogenous GRP78 and
      GRP94 mRNAs compared to wild-type CHO cells. This suggests that GRP78
      overexpression either alleviates the stress or is directly involved in signaling
      stress-induced expression of GRPs. Transient expression of secreted proteins was
      used to measure secretion efficiency in the GRP78 overexpressing cells. Secretion
      of von Willebrand factor and a mutant form of factor VIII, two proteins which
      transiently associate with GRP78, was reduced by GRP78 overexpression. In
      contrast, secretion of M-CSF, which was not detected in association with GRP78,
      was unaffected. This indicates that elevated levels of GRP78 may increase stable
      association and decrease the secretion efficiency of proteins which normally
      transiently associate with GRP78. These results indicate that one function of
      GRP78 is selective protein retention in the ER.

PMID- 1373379
TI  - Analysis of the BiP gene and identification of an ER retention signal in
      Schizosaccharomyces pombe.
AB  - We have cloned the gene for the resident luminal ER protein BiP from the fission
      yeast, Schizosaccharomyces pombe. The predicted protein product is equally
      divergent from the budding yeast and mammalian homologues. Disruption of the BiP
      gene in S. pombe is lethal and BiP mRNA levels are regulated by a variety of
      stresses including heat shock. Immunofluorescence of cells expressing an epitope
      tagged BiP protein show it to be localized to the nuclear envelope, around the
      cell periphery and in a reticular structure through the cytoplasm. Unexpectedly,
      we find the BiP protein contains an N-linked glycosylation site which can be
      utilized. The C-terminal four amino acids of BiP are Ala-Asp-Glu-Leu, a new
      variant of the XDEL sequence found at the C-termini of luminal endoplasmic
      reticulum proteins. To determine whether this sequence acts as a sorting signal
      in S.pombe we expressed an acid phosphatase fusion protein extended at its C
      terminus with the amino acids ADEL. Analysis of the sorting of this fusion
      protein indicates that the ADEL sequence is sufficient to cause the retention of
      proteins in the endoplasmic reticulum. The sequences DDEL, HDEL and KDEL can also
      direct ER-retention of acid phosphatase in S.pombe.

PMID- 1373380
TI  - Subunit stoichiometry and three-dimensional arrangement in proteasomes from
      Thermoplasma acidophilum.
AB  - The proteasome or multicatalytic proteinase from the archaebacterium Thermoplasma
      acidophilum is a 700 kDa multisubunit protein complex. Unlike proteasomes from
      eukaryotic cells which are composed of 10-20 different subunits, the Thermoplasma
      proteasome is made of only two types of subunit, alpha and beta, which have
      molecular weights of 25.8 and 22.3 kDa, respectively. In this communication we
      present a three-dimensional stoichiometric model of the archaebacterial
      proteasome deduced from electron microscopic investigations. The techniques which
      we have used include image analysis of negatively stained single particles, image
      analysis of metal decorated small three-dimensional crystals after freeze-etching
      and STEM mass measurements of freeze-dried particles. The archaebacterial and
      eukaryotic proteasomes are almost identical in size and shape; the subunits are
      arranged in four rings which are stacked together such that they collectively
      form a barrel-shaped complex. According to a previous immunoelectron microscopic
      investigation, the alpha-subunits form the two outer rings of the stack, while
      the two rings composed of beta-subunits, which are supposed to carry the active
      sites, are sandwiched between them. Each of the alpha- and beta-rings contains
      seven subunits; hence the stoichiometry of the whole proteasome is alpha 14 beta
      14 and the symmetry is 7-fold. Image simulation experiments indicate that the
      alpha- and beta-subunits are not in register along the cylinder axis; rather it
      appears that the beta-rings are rotated with respect to the alpha-rings by
      approximately 25 degrees. In contrast to some previous reports we have not been
      able to find stoichiometric amounts of RNA associated with highly purified
      proteolytically active proteasome preparations.

PMID- 1373381
TI  - Intramolecular relationships in cholinesterases revealed by oocyte expression of
      site-directed and natural variants of human BCHE.
AB  - Structure-function relationships of cholinesterases (CHEs) were studied by
      expressing site-directed and naturally occurring mutants of human
      butyrylcholinesterase (BCHE) in microinjected Xenopus oocytes. Site-directed
      mutagenesis of the conserved electronegative Glu441,Ile442,Glu443 domain to
      Gly441,Ile442,Gln443 drastically reduced the rate of butyrylthiocholine (BTCh)
      hydrolysis and caused pronounced resistance to dibucaine binding. These findings
      implicate the charged Glu441,Ile442,Glu443 domain as necessary for a functional
      CHE catalytic triad as well as for binding quinoline derivatives. Asp70 to Gly
      substitution characteristic of 'atypical' BCHE, failed to alter its Km towards
      BTCh or dibucaine binding but reduced hydrolytic activity to 25% of control.
      Normal hydrolytic activity was restored to Gly70 BCHE by additional His114 or
      Tyr561 mutations, both of which co-appear with Gly70 in natural BCHE variants,
      which implies a likely selection advantage for these double BCHE mutants over the
      single Gly70 BCHE variant. Gly70 BCHE variants also displayed lower binding as
      compared with Asp70 BCHE to cholinergic drugs, certain choline esters and
      solanidine. These effects were ameliorated in part by additional mutations or in
      binding solanidine complexed with sugar residues. These observations indicate
      that structural interactions exist between N' and C' terminal domains in CHEs
      which contribute to substrate and inhibitor binding and suggest a crucial
      involvement of both electrostatic and hydrophobic domains in the build-up of the
      CHE active center.

PMID- 1373382
TI  - A glutamate receptor channel with high affinity for domoate and kainate.
AB  - The non-NMDA family of glutamate receptors comprises a growing number of
      structurally related subunits (GluR-A to -D or -1 to -4; GluR-5, -6; KA-1). GluR
      A to -D appear to constitute the major AMPA receptor subtypes but the functional
      and pharmacological characteristics of the other subunits are unresolved. Using a
      mammalian expression system we demonstrate here that homomeric GluR-5 receptors
      exhibit properties of a high affinity domoate (KD approximately 2 nM) and kainate
      (KD approximately 70 nM) binding site. For these receptors, the rank order of
      ligands competing with [3H]kainate binding was domoate much greater than
      quisqualate approximately glutamate much greater than AMPA approximately CNQX.
      The respective receptor channels were gated in decreasing order of sensitivity by
      domoate, kainate, glutamate and AMPA. In contrast to recombinantly expressed GluR
      A to -D channels, currents elicited at GluR-5 receptor desensitize channels to
      all agonists. This property is characteristic of currents in peripheral neurons
      on sensory ganglia. These findings suggest the existence of at least two distinct
      types of non-NMDA receptor channels, both gated by AMPA and kainate, but
      differing in pharmacology and current properties.

PMID- 1373383
TI  - BTG1, a member of a new family of antiproliferative genes.
AB  - The BTG1 gene locus has been shown to be involved in a t(8;12)(q24;q22)
      chromosomal translocation in a case of B-cell chronic lymphocytic leukemia. We
      report here the cloning and sequencing of the human BTG1 cDNA and establish the
      genomic organization of this gene. The full-length cDNA isolated from a
      lymphoblastoid cell line contains an open reading frame of 171 amino acids. BTG1
      expression is maximal in the G0/G1 phases of the cell cycle and is down-regulated
      when cells progress throughout G1. Furthermore, transfection experiments of
      NIH3T3 cells indicate that BTG1 negatively regulates cell proliferation. The BTG1
      open reading frame is 60% homologous to PC3, an immediate early gene induced by
      nerve growth factor in rat PC12 cells. Sequence and Northern blot analyses
      indicate that BTG1 and PC3 are not cognate genes. We then postulate that these
      two genes are the first members of a new family of antiproliferative genes.

PMID- 1373385
TI  - Vogt-Koyanagi-Harada disease presenting meningoencephalitis. Report of a case
      with magnetic resonance imaging.
AB  - A 40-year-old Japanese woman, formerly diagnosed as having Vogt-Koyanagi-Harada
      disease (VKH), developed a consciousness disturbance. There were nuchal rigidity
      and mild right facial weakness. Ophthalmological findings were compatible with
      VKH. Lumbar puncture revealed moderate pleocytosis. MRI showed multiple focal
      lesions. This case verifies parenchymatous involvement of CNS in VKH.

PMID- 1373384
TI  - Sero epidemiological characteristics of hepatitis C encountered in general
      practice in Belgium.
AB  - A study carried out between 1982 and 1984 established by exclusion diagnosis that
      35% of viral hepatitis cases registered in Belgium were due to non A, non B
      (NANB) viruses. Recently, a new anti-hepatitis C virus (HCV) detection test was
      used to analyse the sera of patients in whom NANB hepatitis was diagnosed in that
      study. Using this new serological test for HCV, 29% of the NANB group was found
      to be positive for anti-HCV. In the 1982-84 study on viral hepatitis diagnosed by
      general practitioners, the number of clinically recognized infections was
      estimated at 14,700 (+/- 2,170; confidence interval at 95%) per year. By
      combining these data and the results of the present study, the following
      estimates could be calculated: HAV (7,129 +/- 1,054/year), HBV (2,426 +/-
      358/year), HCV (1,470 +/- 216/year) and non-identified hepatitis viruses (3,675
      +/- 543/year).

PMID- 1373386
TI  - The effects of horizontal tooth loading on the circulation and width of the
      periodontal ligament--an experimental study on beagle dogs.
AB  - The third premolars of Beagle dogs were subjected to tipping force of 20N,
      applied for between 20 minutes and 7 hours. Ten minutes before the end of the
      experiment the animals were injected intravenously with disulphine blue in order
      to show the capillary circulation and the tissue perfusion in the PDL under
      loading. The animals were then killed, and vertical histological sections were
      made of the loaded and the control teeth. The width of the PDL of the loaded and
      control teeth was measured at seven levels along the root surface and an analysis
      of variance was carried out. There was no circulatory disturbance and only slight
      irreversible changes in the shape of the PDL with loading for up to 3 hours. Only
      the teeth which had been loaded for at least 3 hours showed clear zones of
      irreversible compression and expansion. As the amount of irreversible compression
      increased so the blood supply and the circulation were impaired. Further
      increased compression of the periodontal ligament caused by long-term force
      application resulted in localized blood clotting.

PMID- 1373387
TI  - Gene expression in hepatocyte-like lines established by targeted carcinogenesis
      in transgenic mice.
AB  - New hepatocyte-like cell lines (mhAT) were derived from the liver of a transgenic
      mouse expressing SV40 early genes under the direction of the liver-specific
      antithrombin III gene promoter (ATIII-TSV40). Their differentiated phenotypes
      were improved and stabilized by the use of liver-specific growth media (arginine
      free, glucose-free, or low-fructose/glucose-free medium). The best differentiated
      lines display a very high level of albumin, transferrin, and L-type pyruvate
      kinase (L-PK) gene expression that is comparable to that observed in the mouse
      liver. Abundance of the aldolase B and phosphoenolpyruvate carboxykinase (PEPCK)
      transcripts varied from 5 to 35% of the in vivo concentrations while abundance of
      the alpha-fetoprotein and phenylalanine hydroxylase transcripts remained very
      low. Hormonal (cAMP and insulin) and nutritional (glucose) gene controls of PEPCK
      and L-PK were, at least partially, conserved. mhAT cells are readily
      transfectable by the calcium phosphate coprecipitation technique and exhibit a
      liver-specific pattern of expression of exogenous genes. Thus, mhAT cells seem
      suitable for the analysis of the regulatory regions involved in the tissue
      specific transcription of genes. This work demonstrates, therefore, the great
      efficiency of targeted carcinogenesis in transgenic mice to create new
      differentiated cell lines. The availability of various lines of liver-specific
      cells with different phenotypes will constitute useful tools to establish
      correlations between expression of trans-acting factors and control of the
      phenotype.

PMID- 1373388
TI  - cis-4-Hydroxy-L-proline and ethyl-3,4-dihydroxybenzoate prevent myogenesis of
      C2C12 muscle cells and block MyoD1 and myogenin expression.
AB  - cis-4-Hydroxy-L-proline (cis-OH-Pro) and ethyl-3,4-dihydroxybenzoate (EDHB), two
      distinct inhibitors of collagen synthesis, prevented myogenesis in C2C12 mouse
      skeletal muscle cells. Both inhibitors blocked myotube formation and the
      expression of sarcomeric myosin heavy chain. Northern blot analysis showed that
      cis-OH-Pro- and EDHB-treated C2C12 muscle cells did not express the myogenic
      regulatory genes, MyoD1 and myogenin, but continued to express non-muscle
      isoforms of actin (beta and gamma) and alpha-tropomyosin. 10TFL2-3B cells, a
      C3H10T1/2 cell line permanently transfected with myogenin cDNA, constitutively
      expressed exogenous myogenin in the presence of cis-OH-Pro but failed to activate
      endogenous myogenin and to undergo myogenesis. These results demonstrate that
      commitment to terminal differentiation and activation of myogenic regulatory
      genes requires active synthesis of the extracellular matrix component collagen.

PMID- 1373389
TI  - Alveolar accumulation of fibronectin and hyaluronan precedes bleomycin-induced
      pulmonary fibrosis in the rat.
AB  - The development of bleomycin-induced pulmonary fibrosis in rats was studied over
      a period of 30 days after an intratracheal instillation of bleomycin. Fibronectin
      was visualized in histological sections and quantified in bronchoalveolar lavage
      fluid (BALF) and related to simultaneous measurements of hyaluronan, collagen and
      albumin in BALF and/or lung tissue extracts. An increase in BALF fibronectin
      levels was noted after 3 days and the peak value a sixty fold increase was noted
      at day 7. Thereafter, the fibronectin levels declined and reached control values
      on day 21. A pronounced, patchily distributed staining for fibronectin appeared
      in the injured alveolar tissue parallel to the increased lavage fluid fibronectin
      levels on days 3-7. A fainter, streakily distributed fibronectin staining
      remained within the alveolar walls in areas with proliferating fibroblasts on
      days 14-30. Albumin in BALF increased to a peak level, 20 times control values,
      after 3 days and then rapidly declined. Thus, the ratio of fibronectin to albumin
      increased to a peak value of 43 times control values on day 7, indicating that
      plasma leakage cannot be the only source of the observed increase in lavage
      fibronectin. Lung tissue hydroxyproline increased between days 7 and 30, whereas
      extractable hyaluronan in lung tissue and bronchoalveolar lavage fluid peaked on
      days 3-7 and then gradually declined towards normal values on days 21-30. These
      data demonstrate that fibronectin accumulates in the alveolar tissue during the
      early inflammatory phase of the bleomycin-induced lung injury, parallelling
      hyaluronan accumulation and preceding the development of pulmonary fibrosis.

PMID- 1373390
TI  - Characterization of the RDC1 gene which encodes the canine homolog of a proposed
      human VIP receptor. Expression does not correlate with an increase in VIP binding
      sites.
AB  - We have isolated a portion of the canine gene encoding the orphan receptor RDC1
      [1]. The complete coding sequence is contained in a single exon, and an intron
      divides the 5' untranslated region of RDC1 mRNA. The RDC1 protein is 94%
      homologous to the gene product of GPRN1, which has been proposed to serve as a
      VIP receptor when expressed in CHO-K1 and COS-7 cells (Sreedharan, S.P. et al.
      (1991) Proc. Natl. Acad. Sci. USA 88, 4986-4990). Northern analysis indicates
      that CHO-K1 cells endogenously express a 2.1 kb RDC1 mRNA. However, while CHO-K1
      cells possess detectable low affinity [125I]VIP binding sites, VIP binding is not
      altered in membranes of CHO-K1 cells expressing varying amounts of the RDC1 gene
      construct. Further, endogenous VIP binding is not increased by transient
      expression of RDC1 in COS-7 cells. Taken together, the data suggest that RDC1 is
      not a canine homolog of the proposed VIP receptor.

PMID- 1373391
TI  - An interferon-induced protein with release factor activity is a tryptophanyl-tRNA
      synthetase.
AB  - Interferon gamma induces expression of a protein termed IFP 53 according to its
      molecular weight of 53 kDa. IFP 53 shows significant sequence homology to rabbit
      peptide chain release factor as well as to bovine tryptophanyl-tRNA synthetase.
      IFP 53 has been shown to possess release factor activity for the UGA stop codon.
      We demonstrate here, by using a recombinant IFP 53 fusion protein, that IFP 53
      tryptophanylates tRNA. These data indicate that IFP 53 is a protein with two
      activities: peptide chain termination and aminoacylation.

PMID- 1373392
TI  - Isoproterenol-stimulated labelling of particulate proteins by using [adenylate
      32P]NAD+ independent on a cAMP-dependent protein kinase in parotid acinar cells.
AB  - When saponin-permeabilized rat parotid acinar cells were incubated with
      [adenylate-32P]NAD+, labelling of proteins (33, 27 and 23 kDa) in particulate
      fractions of the cells was stimulated by isoproterenol. The effect of
      isoproterenol was completely blocked by a beta-antagonist. Both forskolin or cAMP
      mimicked the effect of isoproterenol on the labelling. However, an inhibitor of
      cAMPdPK failed to induce complete inhibition of the effects of isoproterenol,
      forskolin and cAMP. When the labelled proteins were treated with snake venom
      phosphodiesterase, neither [32P]5'-AMP nor [32P]phosphoribosyladenosine was
      released. These results suggest that covalent modification of proteins with NAD+,
      which is distinct from ADP-ribosylation and cAMPdPK-dependent phosphorylation, is
      coupled to beta-receptor-cAMP signalling system in rat parotid acinar cells.

PMID- 1373393
TI  - Towards continuous glucose monitoring: in vivo evaluation of a miniaturized
      glucose sensor implanted for several days in rat subcutaneous tissue.
AB  - A miniaturized amperometric, enzymatic, glucose sensor (outer diameter 0.45 mm)
      was evaluated after implantation in the subcutaneous tissue of normal rats. A
      simple experimental procedure was designed for the long-term assessment of the
      sensor's function which was performed by recording the current during an
      intraperitoneal glucose load. The sensor was calibrated by accounting for the
      increase in the current during the concomitant increase in plasma glucose
      concentration, determined in blood sampled at the tail vein. This made it
      possible to estimate the glucose concentration in subcutaneous tissue. During the
      glucose load, the change in subcutaneous glucose concentration followed that in
      blood with a lag time consistently shorter than 5 min. The estimations of
      subcutaneous glucose concentration during these tests were compared to the
      concomitant plasma glucose concentrations by using a grid analysis. Three days
      after implantation (n = 6 experiments), 79 estimations were considered accurate,
      except for five which were in the acceptable zone. Ten days after implantation (n
      = 5 experiments), 101 estimations were accurate, except for one value, which was
      still acceptable. The sensitivity was around 0.5 nA.mmol-1.l-1 on day 3 and day
      10. A longitudinal study on seven sensors tested on different days demonstrated a
      relative stability of the sensor's sensitivity. Finally, histological examination
      of the zone around the implantation site revealed a fibrotic reaction containing
      neocapillaries, which could explain the fast response of the sensor to glucose
      observed in vivo, even on day 10. We conclude that this miniaturized glucose
      sensor, whose size makes it easily implanted, works for at least ten days after
      implantation into rat subcutaneous tissue.

PMID- 1373395
TI  - Expression of heterologous peptides at two permissive sites of the MalE protein:
      antigenicity and immunogenicity of foreign B-cell and T-cell epitopes.
AB  - We previously determined a number of 'permissive' sites in the periplasmic
      maltose-binding protein (MalE) from Escherichia coli. These sites accept the
      insertion of heterologous peptides without major deleterious consequences for the
      activities, structure and cellular location of the protein. This study explores
      the versatility of two such permissive sites for the synthesis of foreign
      peptides, and examines the antigenicity and the immunogenicity of the inserts.
      One site is located after amino acid 133 (aa133) of MalE, and the other after
      aa303. Both sites tolerate inserts of up to at least 70 aa and accept sequences
      of different natures. Hydrophobic aa sequences are accepted, although strongly
      hydrophobic sequences, such as the Sendai virus F protein membrane anchor,
      affected export. We compared the antigenic and the immunogenic properties of
      peptides derived from the coat proteins of HBV and poliovirus which contain well
      defined B-cell epitopes. Specific monoclonal antibodies show that the antigenic
      properties of the inserted B-cell epitopes were different at the two sites.
      Despite these differences, the inserted peptides elicited strong and comparable
      antibody responses in mice against the corresponding synthetic peptides. In this
      case, and with these criteria, the molecular context of the peptides did not
      affect the immunogenicity of B-cell epitopes. We show for the first time that
      when a foreign peptide carrying a T-cell epitope was inserted in MalE, the hybrid
      proteins can elicit a T-cell response against the foreign peptide both in vivo
      and in vitro. Furthermore, the MalE hybrid was as efficient as free peptide in
      stimulating T-cell hybridomas in vitro. The MalE vectors provide a powerful
      genetic system to study how the position and the conformation of a peptide within
      a protein affect the B-cell and T-cell responses.

PMID- 1373394
TI  - Expression of an islet regenerating (reg) gene in isolated rat islets: effects of
      nutrient and non-nutrient growth factors.
AB  - The expression of a novel regenerating (reg) gene has been reported previously in
      the regenerating islets of a surgical model of diabetes in rats. We exposed
      collagenase-isolated rat islets for three days to nutrient and non-nutrient
      growth factors in minimally supplemented RPMI medium (2.7 mmol/l glucose, 2%
      fetal calf serum), and investigated the relationship between reg gene expression
      and islet cell replication. RNA was prepared from half of the islets by
      homogenisation in guanidinium isothiocyanate followed by phenol/chloroform
      extraction. Northern/dot blot analyses were used to semi-quantify reg mRNA. Islet
      cell replication was estimated by culturing the remaining islets in radiolabelled
      thymidine to determine de novo DNA synthesis. Thymidine uptake was stimulated by
      the following factors: 11 mmol/l glucose (50% increase); 10% amino acids (126%
      increase); 10% fetal calf serum (39% increase); 100 ng/ml insulin (45% increase);
      250 ng/ml growth hormone (65% increase); 1.5 nmol/l aldosterone (29% increase); 2
      U/ml platelet derived growth factor (116% increase). The results are expressed as
      a percentage of the thymidine incorporated into control islets cultured in
      minimal RPMI (1118 +/- 100 (SD) cpm/microgram protein, n = 15). Increased islet
      cell replication was paralleled in each case by a clear rise in reg mRNA
      expression compared to controls. Furthermore, the rank order for reg gene
      expression was the same as that for thymidine uptake (r = 0.90). The present
      findings suggest a clear association between reg gene expression and islet cell
      replication in vitro, and are the first to demonstrate reg gene expression in
      response to individual growth factors.

PMID- 1373396
TI  - [Interleukins, interferon and the development of the endometrial epithelium].
AB  - The subject of endometrial epithelial growth control by the cytokine system has
      been scantily addressed in the literature. This article analyses the effects of
      cytokines on the endometrium in order to improve our understanding regarding the
      autocrine, paracrine and systemic mechanisms that govern cell differentiation and
      tumor formation in human endometrial epithelial cells.

PMID- 1373397
TI  - Growth fraction in breast carcinoma determined by Ki-67 immunostaining:
      correlation with pathological and clinical variables.
AB  - The growth fractions (GF) of 151 mammary carcinomas were determined in situ by Ki
      67 immunoperoxidase staining. A mean value of 14.6% Ki-67-positive tumor cells,
      with a standard deviation of 11.1, was found. Tumors of histological grades 1 and
      2 had a mean GF of 13.1% which was significantly lower (p less than 0.05) than
      that of grade 3 tumors (mean GF 17.3%). The 14 patients in whom distant
      metastases appeared after primary staging had a significantly higher (p less than
      0.05) GF (21.3%) than the other patients (13.9%). No significant correlation was
      found between GF and concentration of hormone receptors, lymph node status, tumor
      size, or patient's age. Our results suggest that immunostaining with Ki-67 could
      be used as an additional tool to detect breast carcinoma patients with a high
      risk of developing metastases.

PMID- 1373398
TI  - Characterization of a neutralizing monoclonal antibody to Pasteurella haemolytica
      leukotoxin.
AB  - Six hybridoma clones producing monoclonal antibodies (MAbs) reactive with
      Pasteurella haemolytica A1 leukotoxin were derived from mice immunized with
      leukotoxin excised from sodium dodecyl sulfate-polyacrylamide gels. Of the six
      MAbs, only one, Ltx-2, neutralized leukotoxin in a BL-3 cell cytotoxicity assay.
      MAb Ltx-2 blocked association of A1 leukotoxin to BL-3 cells, as measured by flow
      cytometric analysis. The epitope recognized by Ltx-2 was localized to the
      carboxyl half of the native protein, between residues 450 and 939, by Western
      immunoblot analysis of CNBr fragments. Further analysis with leukotoxin deletion
      proteins indicated either that the Ltx-2-reactive epitope was localized in the
      carboxyl portion of the leukotoxin between amino acids 768 and 939 or that this
      region influences MAb recognition of the epitope. MAb Ltx-2 was tested for
      neutralizing activity against leukotoxin produced by P. haemolytica serotypes 1
      through 12. The MAb neutralized leukotoxin produced by all of the A biotype
      isolates (serotypes 1, 5, 6, 7, 8, 9, and 12), with the exception of serotype A2,
      but did not neutralize any T biotype leukotoxin tested (T3, T4, or T10). The
      results indicate that MAb Ltx-2 neutralizes leukotoxin by interfering with target
      cell association and that the MAb-specific epitope is either not present or not
      critical for function in the leukotoxin produced by P. haemolytica serotypes A2,
      T3, T4, and T10.

PMID- 1373399
TI  - Monoclonal secretory immunoglobulin A protects mice against oral challenge with
      the invasive pathogen Salmonella typhimurium.
AB  - Hybridomas producing monoclonal immunoglobulin A (IgA) antibodies against
      Salmonella typhimurium were generated by mucosal immunization of BALB/c mice with
      attenuated strains of S. typhimurium and subsequent fusion of Peyer's patch
      lymphoblasts with myeloma cells. To test the role of secretory IgA (sIgA) in
      protection against Salmonella sp., we analyzed in detail the protective capacity
      of a monoclonal IgA, Sal4, produced in polymeric as well as monomeric forms, that
      is directed against a carbohydrate epitope exposed on the surface of S.
      typhimurium. BALB/c mice bearing subcutaneous Sal4 hybridoma tumors and secreting
      monoclonal sIgA into their gastrointestinal tracts were protected against oral
      challenge with S. typhimurium. This protection was directly dependent on specific
      recognition by the monoclonal IgA, since mice secreting Sal4 IgA from hybridoma
      tumors were not protected against a fully virulent mutant that lacks the Sal4
      epitope. Although monoclonal Sal4 IgA was present in the bloodstreams and tissues
      of tumor-bearing mice, it did not protect against intraperitoneal challenge and
      did not possess complement-fixing or bacteriocidal activity in vitro. Taken
      together, these results indicate that secretion of sIgA alone can prevent
      infection by an invasive enteric pathogen, presumably by immune exclusion at the
      mucosal surface.

PMID- 1373400
TI  - Listeria monocytogenes activation of human peripheral blood lymphocytes:
      induction of non-major histocompatibility complex-restricted cytotoxic activity
      and cytokine production.
AB  - Gram-negative bacteria have been shown to activate human natural killer (NK)
      cells. In this report, we show that the gram-positive bacterium Listeria
      monocytogenes can also activate human NK cells with regard to non-major
      histocompatibility complex (MHC)-restricted killing and the production of
      cytokines. Overnight incubation of peripheral blood mononuclear (PBM) cells or
      enriched NK cell populations with live or Formalin-fixed L. monocytogenes
      resulted in high levels of non-MHC-restricted cytotoxic activity. Listeria
      stimulated non-MHC-restricted cytotoxic activity could be achieved with
      pathogenic as well as nonpathogenic Listeria strains. PBM cells also produced
      tumor necrosis factor alpha and different interferons (IFNs) after incubation
      with Listeria strains. Optimal cytokine production appeared to be dependent on
      nylon wool- and plastic-adherent cells. Different IFNs were produced by Listeria
      stimulated PBM cells obtained from different donors. IFN-gamma was always
      produced but was sometimes associated with IFN-alpha and/or IFN-beta. Interleukin
      2 (IL-2) activity was never detected in culture supernatants obtained from
      Listeria-stimulated PBM cell cultures. However, IL-2 appeared to be produced by
      Listeria-stimulated PBM cells, since antibody to IL-2 inhibited Listeria
      stimulated NK cell cytotoxic activity. Listeria activation of NK cell cytotoxic
      activity was also dependent on tumor necrosis factor alpha production. Antibody
      to IFN-gamma, IFN-beta, or IFN-alpha had no effect on Listeria-stimulated NK cell
      cytotoxic activity. These results demonstrate that NK cells can be activated by
      Listeria strains and add further evidence that NK cells may play an important
      role in host defense against bacterial infections.

PMID- 1373401
TI  - Identification and characterization of B-cell epitopes of IpaC, an invasion
      associated protein of Shigella flexneri.
AB  - Invasion plasmid antigen C (IpaC) is a 43-kDa plasmid-encoded protein associated
      with the ability of shigellae to invade epithelial cells. This protein is
      consistently strongly recognized by sera from convalescent patients and monkeys
      experimentally infected with shigellae. The strong immunogenicity of IpaC in the
      course of natural infection makes it a good candidate as a potentially protective
      antigen. To map the B-cell epitopes of this protein, the gene encoding IpaC was
      cloned and expressed at a high level in Escherichia coli. The partially purified
      recombinant protein was used to raise rabbit polyclonal antisera and murine
      monoclonal antibodies. A lambda gt11 ipaC gene library was screened with the
      antisera and antibodies. Recombinant DNA clones producing specific antigenic
      determinants were isolated, and the sequence of their DNA inserts was determined.
      The amino acid sequence of each determinant was deduced from the minimal overlap
      of DNA inserts of multiple antibody-positive DNA clones. Two distinct epitopes,
      located between amino acid residues 25 and 33 and 90 and 97, were identified. Two
      additional B-cell epitopes which were located between residues 297 and 349, near
      the carboxy-terminal end of the protein, were characterized. Each of these
      epitopes was also recognized by sera from convalescent humans and monkeys.
      Therefore, it seems likely that these epitopes are relevant to the humoral
      response against IpaC during natural infection.

PMID- 1373402
TI  - Fimbriation of Pseudomonas cepacia.
AB  - Fimbriae (pili) on the surface of bacteria have been suggested to facilitate
      adherence to mucosal epithelial surfaces. Three Pseudomonas cepacia cystic
      fibrosis isolates were screened for their ability to agglutinate erythrocytes
      (HA), a characteristic of some fimbrial types. One strain, designated PC103, was
      HA+, while another, PC109, was HA-. A fimbriated (f+) HA+ derivative of PC109
      (PC2(13)) was selected by repeated erythrocyte adsorption. The two HA+ strains
      were shown by transmission electron microscopy to possess fimbriae which averaged
      4.8 +/- 1.36 nm in width and 200 to greater than 2,100 nm in length (PCE2(13))
      and 3.4 to 11.4 nm in diameter and 280 to 720 nm in length (PC103). Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane proteins
      prepared from PC103, PC109, and PCE2(13) indicated that the putative fimbrial
      subunit had a mass of 16 kDa. Western blot (immunoblot) analysis of sheared cell
      supernatants indicated that the 16-kDa subunit from PC103 and PCE2(13) reacted
      with antibody to the P. aeruginosa PAK pilin subunit. Southern blot analysis of a
      SalI digest of PC103 DNA showed DNA fragments which hybridized to P. aeruginosa
      PAK probes containing either the pilin structural gene (pilA) or the pilin
      accessory genes (pilB, -C, and -D) but not the conserved N-terminal region of
      pilA. A 15-kb band was common to both hybridizations, indicating that this
      fragment contains the PC103 fimbrial gene cluster. These results indicated the
      presence of homology between P. aeruginosa PAK and PC103 fimbriae but also
      suggested that the P. cepacia fimbriae are not type IV-like. The importance of
      fimbriae in adherence to A549 cells (type II pneumocytes) was assessed with PC109
      (f-) and PCE2(13) (f+). PCE2(13) had an approximately 20-fold-higher level of
      adherence to A549 cells than PC109. This suggested that fimbriation of P. cepacia
      is associated with increased adherence in vitro.

PMID- 1373403
TI  - Neonatal, urogenital isolates of biotype 4 nontypeable Haemophilus influenzae
      express a variant P6 outer membrane protein molecule.
AB  - The P6 outer membrane protein is a highly conserved molecule which is present on
      the surface of all strains of Haemophilus influenzae. Sixty strains of
      nontypeable H. influenzae which caused invasive disease or colonized the female
      urogenital tract were studied with monoclonal antibodies 7F3 and 4G4, which
      recognize different surface-exposed epitopes on the P6 molecule. All 60 strains
      expressed the epitope recognized by 4G4, whereas 47 of 60 strains expressed the
      epitope recognized by antibody 7F3. The 7F3-nonreactive strains were all biotype
      4 and were recovered from the blood of neonates or postpartum women or from the
      female urogenital tract. The P6 genes from two 7F3-nonreactive strains were
      cloned, and the nucleotide sequences were determined. Analysis of amino acid
      sequences, immunoassays with synthetic peptides, and site-directed mutation of
      the P6 gene indicate that the epitope recognized by antibody 7F3 is
      conformational and that the sequence Asp-Ile-Thr is critical in maintaining the
      conformation of the epitope. We conclude that the unusually virulent clone family
      of biotype 4 strains of nontypeable H. influenzae express a variant P6 molecule
      which has an alteration in a highly conserved surface-exposed epitope.

PMID- 1373404
TI  - Demonstration of chlamydial RNA and DNA during a culture-negative state.
AB  - Trachoma is a common blinding disease of humans caused by ocular infections with
      Chlamydia trachomatis. The cynomolgus monkey is a valuable primate model for the
      detection, pathobiology, and treatment of this infection. We have used this model
      system to compare the relative ability of tissue culture, direct fluorescence
      cytology, a modified polymerase chain reaction, and RNA blotting to detect C.
      trachomatis following primary infection and reinfection over 34 weeks. Six
      cynomolgus monkeys were given a primary ocular chlamydia infection, and 20 weeks
      later they were reinoculated with the same organism. All animals showed brisk
      inflammatory responses to the primary infection and milder inflammatory reactions
      to reinfection. All four diagnostic techniques detected chlamydia at 1 week after
      primary infection, but both nucleic acid detection methods suggested that
      organisms were present longer after primary infection than did either tissue
      culture or direct fluorescence cytology (16 weeks for RNA blotting versus 12
      weeks for tissue culture). Following reinoculation at 20 weeks, the period of C.
      trachomatis detection by tissue culture or direct fluorescence cytology (4 weeks)
      was much shorter than after primary infection. In contrast, nucleic acid
      detection was positive for up to 5 weeks longer than tissue culture or direct
      fluorescence cytology. Both polymerase chain reaction and RNA blotting, which
      involved no amplification step, indicated the presence of organisms during the
      culture-negative period. These data suggest that live chlamydiae may remain at a
      site of infection and produce inflammation beyond the time at which standard
      microbiological techniques are able to detect them.

PMID- 1373405
TI  - Evidence for oligomannosyl residues containing both beta-1,2 and alpha-1,2
      linkages as a serotype A-specific epitope(s) in mannans of Candida albicans.
AB  - In order to identify the branches containing both beta-1,2 and alpha-1,2 linkages
      as the serotype A-specific epitope(s) in the mannans of Candida albicans,
      serotype A strains with oligosaccharides constituting the beta-1,2 linkage, the
      alpha-1,2 linkage, and both the beta-1,2 and the alpha-1,2 linkages were prepared
      from the mannans of C. albicans serotype A strains (NIH A-207 and J-1012) and
      tested for their inhibitory effects in the precipitin and slide agglutination
      assays. The results indicated that two oligosaccharides containing both beta-1,2
      and alpha-1,2 linkages, Manp beta 1-2Manp alpha 1-2Manp alpha 1-2Manp alpha 1
      2Man and Manp beta 1-2Manp beta 1-2Manp alpha 1-2Manp alpha 1-2Manp alpha 1-2Man,
      served as epitopes participating in the serotype A specificity of C. albicans
      strains.

PMID- 1373406
TI  - Mapping of functional regions of Clostridium perfringens type A enterotoxin.
AB  - Studies were conducted to allow construction of an initial map of the structure
      versus-function relationship of the Clostridium perfringens type A enterotoxin
      (CPE). Removal of the N-terminal 25 amino acids of CPE increased the primary
      cytotoxic effect of CPE but did not affect binding. CPE sequences required for at
      least four epitopes were also identified.

PMID- 1373408
TI  - Prevalence of antibodies to hepatitis C virus in Italian health care workers.

PMID- 1373407
TI  - Significant role of an exocellular protease in utilization of heme by Vibrio
      vulnificus.
AB  - Clinical and environmental isolates of Vibrio vulnificus could grow in a
      synthetic medium supplemented with heme protein as the iron source. Protease
      deficient mutants of the bacterium could not utilize any of the heme proteins in
      the synthetic medium, but the addition of purified V. vulnificus protease
      restored their growth. The protease digested all heme proteins tested and
      elicited heme liberation from the proteins. Furthermore, the induction of
      protease production by the heme proteins was demonstrated. These observations
      suggest that protease contributes to the efficient utilization of heme by V.
      vulnificus.

PMID- 1373409
TI  - Anti-HCV antibodies in household contacts of patients with cirrhosis of the liver
      -preliminary results.

PMID- 1373410
TI  - Treatment of intracranial human glioblastoma by direct intratumoral
      administration of 131I-labelled anti-tenascin monoclonal antibody BC-2.
AB  - Ten patients with bulky brain glioblastoma, recurring after surgery, radiotherapy
      or chemotherapy, underwent direct intralesional radioimmunotherapy (RIT) using a
      monoclonal antibody (MAb), BC-2, raised against tenascin and labelled with 131I.
      Tenascin, the BC-2-recognized glycoprotein, is an antigen expressed by the stroma
      of malignant gliomas but not by normal cerebral tissue. Preliminary studies in
      animals have demonstrated the ability of anti-tenascin radiolabelled MAbs to
      detect and reduce tumours. A mean MAb dose of 1.93 mg (corresponding to 551.3 MBq
      of 131I) was injected directly into the tumour by means of a stereotaxic
      technique. Both systemic and local toxicity were negligible. After 24 hr, average
      tumour BC-2 uptake was 4.9% per gram and its effective half-life in neoplastic
      tissue was 66.5 hr: a mean radiation dose to target tissue of 36.48 cGy per MBq
      of injected 131I was delivered. Normal brain tissue and the major organs were
      spared. Most patients underwent multiple injections, reaching a cumulative tumour
      radiation ranging from 7,000 to 41,000 cGy. RIT failed to achieve any result in 4
      of the 10 patients; in 3, the disease was stabilized; in the remaining 3, CT scan
      or NMR revealed 2 partial remission (greater than 50% reduction in tumour volume;
      PR) and I complete remission (CR). One patient with PR relapsed after II months;
      the other 2 patients were still maintaining their responses at the time of
      writing, 17 (CR) and 12 (PR) months after injection.

PMID- 1373411
TI  - Triggered activity as the proposed mechanism of left atrial tachycardia induced
      by premature ventricular beats.
AB  - In a 57-year-old woman with complex ventricular ectopy, a paroxysmal
      supraventricular tachycardia initiated by premature ventricular beats is
      presented. She underwent an electrophysiologic study. The tachycardia origin was
      localised to the left atrium. At the presence of retrograde dual atrioventricular
      nodal pathway, the atrial tachycardia was induced by programmed ventricular
      stimulation. Triggered activity was shown to be the likely mechanism of both
      atrial and ventricular arrhythmias.

PMID- 1373412
TI  - Neuropeptides and the conduction system of the heart.

PMID- 1373413
TI  - Nucleolar organizer regions in ovarian tumors: discrimination between carcinoma
      and borderline tumor.
AB  - Nonhistone nucleoproteins associated with the nucleolar organizer region (NOR)
      can be visualized by a silver-staining technique on paraffin-embedded tissues.
      The number of black dots (Ag NORs) appearing on the nuclei are thought to reflect
      cell differentiation of certain tumors and can be used as an adjunct in
      predicting their evolution. We applied this method to determine if Ag NORs counts
      could be used as a diagnostic aid in borderline tumors of the ovary. Thirty-two
      cases of adenocarcinomas, 25 cases of borderline tumors, and 14 cases of adenomas
      were selected from Bouin-fixed archival material after histological examination.
      Both mean values of Ag NORs counts demonstrated a progressive increase from
      adenomas to borderline tumors and to carcinomas; the differences were
      statistically significant. Using discriminant analysis, all cases of benign and
      malignant tumors except one adenoma and one carcinoma were discriminated as
      belonging to an individualized group. No difference was found between borderline
      tumor with peritoneal implants and those without peritoneal implants. The results
      indicate that the Ag NORs counting procedure may be useful in distinguishing
      borderline tumors from carcinomas and adenomas. Ag NORs counts cannot, however,
      predict the clinical behavior of borderline tumors of the ovary.

PMID- 1373414
TI  - The solid variant of adenoid cystic carcinoma of the cervix.
AB  - We studied seven examples of the solid variant of adenoid cystic carcinoma of the
      uterine cervix in postmenopausal women who presented with vaginal bleeding and a
      large ulcerated or polypoid cervical mass. The tumors lacked the characteristic
      cribriform pattern of conventional adenoid cystic carcinoma. The neoplastic cells
      were small, undifferentiated, or basaloid and grew in cords, nests, trabeculae,
      and nodules. Foci of squamous cell carcinoma were seen in three tumors and areas
      of necrosis in four. A characteristic feature was the production of abundant
      periodic acid-Schiff's procedure (PAS)-positive basement membrane material that
      was immunoreactive for collagen IV and that in some areas compressed tumor cells.
      Electron microscopy on three cases showed globules and cylinders of redundant
      basal lamina. The tumor cells were joined by desmosomes and contained bundles of
      tonofilaments. Material similar to basement membrane material appeared to be
      intracytoplasmic in two tumors. No neurosecretory granules or myoepithelial cells
      were found. Four deaths were tumor related. Two patients are currently alive, but
      with local recurrence or metastases; another is alive and well 19 months after
      surgery. We believe that the solid variant of adenoid cystic carcinoma of the
      cervix is a distinctive neoplasm that should be separated from small cell
      carcinomas with or without endocrine features, adenoid basal cell carcinoma, and
      squamous cell carcinoma.

PMID- 1373415
TI  - Patterns of keratin subsets in normal and abnormal uterine cervical tissues. An
      immunohistochemical study.
AB  - We investigated the use of three monoclonal antikeratin antibodies on routinely
      formalin-fixed and paraffin-embedded punch and cone biopsies of the normal human
      uterine cervix and its metaplastic and premalignant lesions. Monoclonal
      antibodies used were AE8, which is specific for keratin 13; 34BE12, which reacts
      with keratins of the stratified squamous epithelium; and CAM5.2, which is
      specific for keratin 8. All these antibodies performed well in routinely
      processed surgical pathology material. AE8 antibody stained the suprabasal layer
      of the normal squamous epithelium. Squamous metaplasia and dysplasia were stained
      in 50% of the cases. Normal suprabasal distribution of the keratin 13, however,
      was lost in all positive dysplasia cases. CAM5.2 reacted with normal columnar
      cells in all cases, and squamous metaplasia was focally positive in 20% of the
      cases. Dysplasia showed a positive reaction in 30% to 40% of the cases. The
      34BE12 antibody was reacting with the full thickness of the squamous epithelium.
      Squamous metaplasia and dysplasia were positive in 80% of the cases. In addition,
      34BE12 stained reserve cell hyperplasia, making it a useful marker for this
      condition. Our results demonstrate that keratin immunohistochemistry with the
      above-listed antibodies gives pathogenetically interesting information on
      cervical lesions.

PMID- 1373416
TI  - Effect of the substitutions in the alpha helix and the beta sheet of HLA class I
      molecule on allorecognition of T cells specific for HLA-B51 and HLA-Bw53.
AB  - HLA-B51 and HLA-Bw53 differ by eight amino acids on the alpha 2 domain. Of these
      eight amino acid substitutions, two are in the alpha helix and six are in the
      beta sheet. The effect of these substitutions on allorecognition of HLA-B51
      specific cytotoxic T lymphocyte (CTL) clones and HLA-Bw53-specific CTL clones was
      investigated using chimeric antigen (Ag) between HLA-B51 and HLA-Bw53. Of 12 HLA
      B51-specific CTL clones, recognition of one clone was abolished by the
      substitutions on the beta sheet alone, that of two clones by the substitutions on
      the alpha helix alone, and that of nine clones not only by the substitutions on
      the alpha helix but also by those on the beta sheets. On the other hand, of 17
      HLA-Bw53-specific CTL clones, recognition of 10 clones was affected by the
      substitutions on the alpha helix alone and that of 7 clones not only by the
      substitutions on the alpha helix but also by those on the beta sheet. The present
      study demonstrated that the substitutions (residues 152 and 171) on the alpha
      helix critically affect recognition of HLA-B51-specific CTL clones and HLA-Bw53
      specific CTL clones and that the substitutions on the beta sheet affect also
      recognition of the majority of HLA-B51-specific CTL clones and 40% of HLA-Bw53
      specific CTL clones. These results indicate that the substitutions at the floor
      of the peptide binding groove affect recognition of allogeneic CTL.

PMID- 1373418
TI  - The role of medical instructional resources in a three-year systems-based
      curriculum.
AB  - This article focuses on a unique method of approaching medical education. It
      outlines the role of a service-based medical instructional resources unit within
      a three-year curriculum and emphasizes the consolidation of an instructional
      philosophy in one centralized learning resource center. This dynamic approach
      incorporates the evolving technological tools of communication and may serve as a
      model for other educational institutions considering a break from a traditional
      four-year rigid curriculum to a more flexible, self-paced learning environment.

PMID- 1373417
TI  - Effect of a supply of raw or extruded rapeseeds on digestion in dairy cows.
AB  - The influence of extruded oilseeds on total tract digestibility and ruminal
      digestion in dairy cows was studied in three cows fed a hay-concentrate
      (60.5/39.5; 3.7% fatty acids in diet on DM basis) control diet (C) or the same
      diet supplemented with raw (R) or extruded (ER) rapeseeds (8.0% fatty acids in
      diet DM). The experimental design was a 3 x 3 Latin square design. Compared with
      diet C, diets containing rapeseed decreased ruminal OM digestibility (9.5%, P
      less than .10) and increased (P less than .05) the proportion of propionate in
      ruminal fluid VFA. Extrusion had no effect on DM and OM total tract
      digestibilities and increased (P less than .10) N digestion. Microbial N flow at
      the duodenum was calculated taking into account solid-adherent bacteria (SAB) and
      liquid-associated bacteria (LAB). Duodenal flows of total, SAB, and LAB of OM and
      N did not change with diet. Extrusion of the rapeseeds did not modify (P less
      than .10) the proportion of bacterial N at the duodenum and had no effect on
      crude fiber digestibility. This trial demonstrates that rapeseeds in hay-based
      diets can be fed at levels of up to 14% of the diet without adversely affecting
      crude fiber digestibility.

PMID- 1373419
TI  - Validation of a high-performance liquid chromatographic-radioimmunoassay method
      for the determination of lacidipine in plasma.
AB  - A sensitive and reproducible method for the determination of lacidipine, a new
      potent antihypertensive dihydropyridine, is reported. The method involves solid
      phase extraction, reversed-phase high-performance liquid chromatography and
      radioimmunoassay of the collected fraction. The assay provides a limit of
      detection of 20 pg/ml of plasma, allowing the determination of trough (24 h)
      plasma concentrations. The method is suitable for pharmacokinetic studies in man.

PMID- 1373420
TI  - Dispersion of monophasic action potential duration: demonstrable in humans after
      premature ventricular extrastimulation but not in steady state.
AB  - Abnormal dispersion of repolarization may contribute to the arrhythmogenic
      physiologic substrate of ventricular arrhythmia. Geographic dispersion of
      monophasic action potential duration was determined in steady state (drive cycle
      lengths 600 and 430 ms) between widely spaced right ventricular endocardial sites
      (geographic dispersion) in 10 control patients with right ventricular disease and
      complicating ventricular tachycardia (n = 9), 6 patients with right and left
      ventricular disease and complicating ventricular tachycardia and 7 patients with
      ischemic heart disease and complicating ventricular tachycardia. No significant
      difference in geographic dispersion could be demonstrated among the groups.
      Difference of monophasic action potential duration at adjacent right ventricular
      endocardial sites (adjacent dispersion) was determined after ventricular
      extrastimulation during construction of simultaneous electrical restitution
      curves in the same patient groups. Maximal adjacent dispersion over the
      electrical restitution curve was compared between disease and control groups.
      There was a significant difference in observations of maximal adjacent dispersion
      in patients with right ventricular disease and complicating ventricular
      tachycardia (range 5 to 85 ms, median 22.5; 14 pairs of sites; p less than 0.05)
      and patients with right and left ventricular disease and complicating ventricular
      tachycardia (range 5 to 50 ms, median 17.5; 14 pairs of sites; p less than 0.05)
      compared with control patients (range 5 to 20 ms, median 10; 15 pairs of sites).
      This difference was not evident when patients with ischemic heart disease and
      complicating ventricular tachycardia (range 5 to 25 ms, median 12.5; 12 pairs of
      sites) were compared with control patients. Maximal percent monophasic action
      potential shortening from steady state was significantly greater (p less than
      0.001) in both groups with greater adjacent dispersions, and prolongation of
      activation time at monophasic action potential recording sites after premature
      extrastimulation tended to be greater in patients with right or right and left
      ventricular disease and complicating ventricular tachycardia. It is concluded
      that in disease, exaggeration of monophasic action potential shortening after
      premature ventricular extrastimulation may contribute to the electrophysiologic
      arrhythmogenic substrate.

PMID- 1373421
TI  - Hepatic resection is not enough for hepatocellular carcinoma. A follow-up study
      of 92 patients.
AB  - We followed up 92 patients who underwent curative hepatic resection for
      hepatocellular carcinoma between 1982 and 1991. The long-term survival rates for
      these 92 patients for 1, 3, and 5 years were 98.8, 81.6, and 57.3%, respectively.
      As of May 1991, the carcinoma had recurred in 52 patients (56.5%). Recurrent
      tumors usually occurred in the residual liver within 3 years after surgery but
      were not always located near the primary lesion. The biologic characteristics of
      the primary tumors, such as serum alpha-fetoprotein, tumor size, number of
      tumors, and portal involvement, were closely related to recurrence and long-term
      survival. However, the type of hepatectomy performed on the primary tumor had
      little influence on recurrence or long-term survival. We conclude that recurrence
      cannot be avoided by hepatic resection alone, much less with limited resection;
      postoperative positive adjuvant therapy is required to prevent recurrence for
      patients with satellite nodule and/or portal involvement.

PMID- 1373422
TI  - Application and assessment of cloacin typing of Enterobacter cloacae.
AB  - Three methods, O-serotyping, phage typing and susceptibility to bacteriocins,
      were used to type 357 clinical isolates of Enterobacter cloacae cultured from 219
      patients. One hundred and sixty isolates were typed by serology and phage typing.
      When these two methods were used, primary classification of isolates was based on
      serology (65.7% typable) and phage typing for further subdivision (94.1%
      typable). When all the isolates were typed by cloacin susceptibility, 81.5% of
      them were typable. Maximum discrimination between cultures was achieved when the
      three methods were used together; no single method was sufficiently
      discriminatory. There was a close parallel between serotyping and bacteriocin
      lysis pattern. The latter was easy to perform and the results were achieved
      within 48 h. By applying this typing system two episodes of cross-infection were
      identified in a haematology/oncology unit and intensive care unit.

PMID- 1373423
TI  - Serodiagnosis of hepatitis C virus infection by ELISA for antibodies against the
      putative core protein (p20c) expressed in Escherichia coli.
AB  - The putative core gene of hepatitis C virus (HCV) was incorporated into a plasmid
      vector (pCC5-J4), and expressed in Escherichia coli. The product of 180 amino
      acids (p20c) was purified by gel electrophoresis in the presence of sodium
      dodecyl sulfate, and used in enzyme-linked immunosorbent assay for antibodies
      against the putative core protein of HCV (anti-p20c). Anti-p20c was detected in
      13 (1.5%) of 873 apparently healthy blood donors. It was detected in 205 (86.5%)
      of 237 patients with acute or chronic non-A, non-B (NANB) hepatic disease,
      significantly more frequently (p less than 0.01) than antibodies against the C100
      3 protein encoded by nonstructural regions of HCV (anti-C100-3) that was found in
      178 (75.1%). Anti-p20c developed in the circulation of a patient with acute NANB
      hepatitis much earlier than anti-C100-3. HCV RNA was detected by polymerase chain
      reaction in serum samples from blood donors positive for anti-p20c in high
      titers, one of which was negative for anti-C100-3. These results indicated that
      anti-p20c would be useful in complementing anti-C100-3 for the diagnosis of NANB
      hepatitis and further decreasing the incidence of posttransfusion NANB hepatitis.

PMID- 1373424
TI  - Immunoassay of type IV collagenase/gelatinase (MMP-2) in human plasma.
AB  - We have developed a sensitive and specific sandwich type enzyme-linked
      immunosorbent assay (ELISA) to detect type IV collagenase (MMP-2) in human plasma
      which employs the combination of affinity purified rabbit polyclonal antibodies
      and mouse monoclonal antibodies to human MMP-2. The MMP-2 ELISA detects latent
      and activated MMP-2, MMP-2 complexed with TIMP and MMP-2 complexed with alpha 2
      macroglobulin (65% efficiency). To determine whether physiologic conditions
      associated with increased connective tissue turnover are accompanied by increased
      MMP-2 levels in plasma, we compared enzyme levels in pregnant and nonpregnant
      women. Plasma MMP-2 (mean +/- standard deviation) was significantly increased (p
      less than 0.05) in the second half of pregnancy (650 +/- 312) as compared to
      early pregnancy (356 +/- 139) or the nonpregnant state (387 +/- 193). As a result
      of the linkage between type IV collagenase production by cancer cells and the
      metastatic phenotype, the assay of MMP-2 in plasma is of potential clinical value
      in cancer.

PMID- 1373425
TI  - Increased frequency of both total and specific monoclonal antibody producing
      hybridomas using a fusion partner that constitutively expresses recombinant IL-6.
AB  - The addition of auxiliary feeder cells or conditioned medium has been shown to
      augment the yield of mouse hybridomas obtained following the cell-cell fusion of
      myeloma and B lymphocytes. The addition of one of these factors, interleukin-6
      (IL-6) has been found to increase the proportion of hybridomas secreting
      monoclonal antibodies of desired specificity. As an alternative genetic approach,
      we have examined the efficacy of a retroviral infectant of Sp2/0 cells that
      constitutively expresses recombinant murine IL-6 (Sp2/mIL-6) as fusion partner.
      The results demonstrated that the yields of both viable Ig-secreting hybridomas,
      and antigen-specific monoclonal antibodies were increased 3-15-fold and 5-9-fold,
      respectively, with the Sp2/mIL-6 relative to Sp2/0 or Sp2/neo cells as fusion
      partner. Sp2/mIL-6 cells generated hybridomas with comparable growth rates,
      stability, and Ig production. The results of staining nascent hybridoma colonies
      immunohistochemically for Ig production suggest that Sp2/mIL-6 cells as a fusion
      partner increased the viability and/or stability of nascent hybrid cells that are
      producing Ig. Thus the Sp2/mIL-6 cells are an improved myeloma parent for the
      generation of large numbers of antibody-producing hybridomas against specific
      antigens.

PMID- 1373426
TI  - Detection of tumor necrosis factor induced nuclear damage with p
      phenylenediamine.
AB  - A simple technique has been used to observe the effects of rTNF alpha on nuclear
      morphology. Using the intercalating dye p-phenylenediamine to stain nuclei, we
      detected TNF alpha-induced nuclear alterations which characteristically occur
      during apoptosis in the TNF alpha sensitive U937 cell line. Nuclear alterations
      were visible prior to the loss of plasma membrane integrity and subsequent cell
      death. A subclone of U937 cells was isolated in which TNF alpha failed to alter
      either cell viability or nuclear morphology. TNF alpha resistant U937 cells,
      however, retained the ability to bind, internalize and degrade TNF alpha. These
      results suggest that nuclear damage induced by TNF alpha in sensitive U937 cells
      occurs early and precedes cell death as measured by dye exclusion assays.
      Staining cells with p-phenylenediamine and visualization with a 520 nm
      fluorescence filter provides a rapid and simple method to monitor apoptotic cell
      death.

PMID- 1373427
TI  - A sensitive and specific competition microELISA for the immunoactive polypeptide
      parathymosin and detection of this peptide in porcine tissues.
AB  - A sensitive and specific microELISA assay is described for the immunoactive
      polypeptide parathymosin. Antibodies against a synthetic peptide corresponding to
      the rat parathymosin sequence 5-30 were raised in rabbits immunised with this
      peptide conjugated to keyhole limpet hemocyanin (KLH). The useful range of the
      assay was 0.25-30 pmol (3-330 ng) of parathymosin and the assay was specific. The
      related immunoactive polypeptides prothymosin alpha or thymosin alpha 1 showed no
      cross-reactivity. In spiking experiments the recovery of the assay was found to
      be greater than 92% at all concentrations tested. The intra-assay variation was
      17%, whereas the inter-assay variation was 26%. Using this assay the highest
      concentration of parathymosin was found in porcine liver, followed by kidney,
      lung, thymus and spleen. This assay compares favorably with one microELISA and
      two RIA methods already published, in that it is more sensitive by at least an
      order of magnitude, and it is simpler and quicker.

PMID- 1373429
TI  - Multimodality treatment in stage IV squamous cell carcinoma of the head and neck.
      A long-term follow-up.
AB  - We treated 114 patients with advanced inoperable head and neck cancer with a
      combined-modality protocol that included two cycles of chemotherapy followed by
      radiotherapy or three chemotherapy and in 18 patients with a radiosensitizing
      agent. At the beginning of the treatment all but one patient presented with a
      stage IV cancer. With a follow-up of 42-58 months, four patients are alive (three
      from the radiosensitizing group and one of the chemotherapy group). Complete
      response after the radiosensitizing agent correlated with superior prolonged
      disease-free survival in comparison to complete responses after chemotherapy at
      the level of p less than 0.009.

PMID- 1373428
TI  - [Studies on biological characteristics of undifferentiated carcinoma of the
      esophagus].
AB  - To study the biological characteristics of undifferentiated carcinoma of the
      esophagus, the nuclear DNA content, the growth fraction using monoclonal antibody
      Ki-67 (Ki-67), immunohistochemical expression of epidermal growth factor receptor
      (EGFR) and the grade of Leu-7 positive cells infiltrating at the marginal area of
      the cancerous tissue were measured in 5 cases of undifferentiated carcinoma and
      131 cases of squamous cell carcinoma. The following results were obtained. 1) DNA
      aneuploid was found in 60% of undifferentiated carcinoma, 47% of squamous cell
      carcinoma. 2) The Ki-67 labeling rates of undifferentiated carcinoma were higher
      than those of squamous cell carcinoma, and a variable proportion of Ki-67
      labeling rates of undifferentiated carcinoma was ranging from 12% to 34%. It was
      demonstrated that undifferentiated carcinoma had high proliferative potential. 3)
      The expression of the EGFR was stained in the basal cell and parabasal layers of
      normal epithelia. In squamous cell carcinoma, EGFR was located on the cancer cell
      membrane and was observed 79%, while in all cases of undifferentiated carcinoma,
      it was not detected. 4) The grade of Leu-7 positive cells was related to
      pathological stage and prognosis in squamous cell carcinoma. The patients with
      low grade of Leu-7 positive cells frequently had early recurrences of the
      carcinoma after esophagectomy, and their prognosis was poorer than those with
      higher grade of Leu-7 positive cells. The patients of undifferentiated carcinoma,
      independently of pathological stage, were observed low grade of Leu-7 positive
      cells and had poor prognosis except only one case. Therefore undifferentiated
      carcinoma seems to be escaped from defensive mechanism of host immune
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373430
TI  - Charcot-Leyden crystal protein in the degranulation and recovery of activated
      basophils.
AB  - The Charcot-Leyden crystal (CLC) protein, a prominent cell constituent unique to
      eosinophils and basophils, possesses lysophospholipase activity. This activity
      and the extracellular deposition and formation of CLC in tissues and body fluids
      in association with eosinophils suggest an extracellular function for this
      protein in inflammation. During degranulation, basophils release granule-derived
      mediators of inflammation. We postulated that CLC protein, localized in part to
      the basophil granule, might be released along with other mediators during this
      process. The extracellular release of CLC protein was studied during the
      degranulation of basophils stimulated by anti-immunoglobulin E (anti-IgE), N
      formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate,
      eosinophil major basic protein (MBP), and calcium ionophore A23187. Histamine
      release was used as a marker of basophil degranulation; its release was measured
      utilizing the fluorometric technique. CLC protein was not released into the
      supernatant during this process as determined by radioimmunoassay. CLC protein in
      the extracellular space, either as intact crystals or aggregates, was
      undetectable by indirect immunofluorescent staining of basophils activated with
      either anti-IgE or fMLP. However, upon activation, the immunofluorescent
      cytoplasmic and nuclear staining pattern for CLC protein was significantly
      altered. Decreased cytoplasmic staining and persistent or increased nuclear
      staining for CLC protein were observed after activation, with recovery of the
      preactivation, unstimulated cellular staining pattern at 30 and 45 min after
      stimulation with fMLP and anti-IgE, respectively. These findings suggest that CLC
      protein functions intracellularly in basophils during the process of activation,
      degranulation, and recovery. The potential nuclear function(s) of this
      lysophospholipase in the basophil requires further investigation.

PMID- 1373431
TI  - Enhanced neutrophil respiratory burst as a biological marker for manipulation
      forces: duration of the effect and association with substance P and tumor
      necrosis factor.
AB  - A critical need in assessing the clinical utility of manipulative therapy for
      back pain is the identification of biological changes associated with the forces
      applied by spinal manipulation. Such changes could then serve as markers for both
      sham treatment and manipulation. We determined the priming of polymorphonuclear
      neutrophils for an enhanced respiratory burst and its duration, the priming of
      mononuclear cells for enhanced endotoxin-stimulated tumor necrosis factor
      production and plasma levels of substance P following a single thoracic spine
      manipulation. There was a significant difference in the respiratory burst of
      polymorphonuclear neutrophils in response to a particulate challenge, depending
      on the time of blood sample collection. The response of polymorphonuclear
      neutrophils isolated from blood collected 15 min after manipulation was
      significantly higher than the response of cells isolated from blood collected 15
      min before and 30 and 45 min after manipulation. Mononuclear cells were also
      primed for enhanced endotoxin-stimulated tumor necrosis factor production by
      spinal manipulation. Both of these priming effects were accompanied by a slight,
      but significant elevation in plasma substance P. The mean manipulation force
      associated with these biological effects was 878 +/- 99 N. These biological
      effects may provide a means of monitoring the delivery of both sham and
      manipulative treatment and, therefore, provide a crucial tool for understanding
      the efficacy of manipulative therapy.

PMID- 1373432
TI  - Substance P: multifunctional peptide in the hypothalamo-pituitary system?

PMID- 1373433
TI  - Effect of growth hormone treatment on the distribution of insulin-like growth
      factor-I between plasma and lymph of lactating sheep.
AB  - Plasma and mammary efferent lymph concentrations of insulin-like growth factor I
      (IGF-I) were determined in lactating ewes before and after treatment with GH (10
      mg/day) for 3 days. The lymph:plasma ratio of IGF-I increased from 0.34 to 0.47
      after GH treatment when the IGF-I content of plasma increased by 19.4 nmol/l
      (from 32.1 nmol/l) and lymph by 13.7 nmol/l (from 10.7 nmol/l). This increase in
      the relative content of IGF-I in lymph was associated with increased lymph
      content of IGF-I in a lower molecular mass pool (nominally 50 kDa) derived by
      size exclusion chromatography. GH treatment increased the total binding capacity
      for IGF-I in both high (150 kDa) and low (50 kDa) molecular mass pools of plasma
      and the 150 kDa pool in lymph but there was a proportionally greater increase in
      50 kDa total binding in lymph relative to plasma. Further, GH treatment increased
      the 'saturation' of the 50 kDa binding proteins but decreased the 'saturation' of
      the 150 kDa fraction, in both plasma and lymph. Ligand blot analysis of IGF
      binding proteins (IGFBPs) in plasma and lymph showed that GH treatment of
      lactating sheep increased IGFBP-3 and decreased IGFBP-2 in plasma and lymph.
      Radioimmunoassay of IGFBP-2 showed that while GH treatment reduced the plasma
      content of IGFBP-2 by about half, the lymph:plasma ratio was increased from 0.68
      to 0.87. GH treatment of lactating ewes not only increased the IGF-I content of
      plasma but increased the apparent efficiency of transfer of IGF-I across
      capillary endothelium to mammary efferent lymph.

PMID- 1373434
TI  - Antigenic analysis of iron-regulated proteins in Pasteurella haemolytica A and T
      biotypes by immunoblotting reveals biotype-specific epitopes.
AB  - The antigenic relationships of the iron-regulated proteins (IRPs) in Pasteurella
      haemolytica A and T biotype strains were examined by SDS-PAGE and immunoblotting.
      P. haemolytica cells of the A biotype, grown under conditions of iron-limitation,
      expressed two IRPs, of 35 and 70 kDa. All T biotype strains expressed IRPs with
      slightly different molecular masses of 37 and 78 kDa. Immunoblotting of all 16 P.
      haemolytica serotypes was carried out using a panel of polyclonal and monoclonal
      antibodies raised against serotype A2 antigens. Polyclonal antibodies revealed
      inter-serotype cross-reactivity towards the 35 and 70 kDa IRPs within the A
      biotype but no cross-reactivity against a T biotype protein in the 78 kDa region.
      Monoclonal antibody against the 35 kDa antigen reacted only with the A biotype 35
      kDa IRP. Identical profiles were obtained for 10 field isolates of serotype A2,
      further emphasizing the antigen conservation within the A biotype. These findings
      reinforce the view that the A and T biotypes of P. haemolytica should be
      considered as separate species and suggest that IRPs from single A and T biotype
      strains incorporated into a vaccine might provide cross-protection against all P.
      haemolytica serotypable strains. Similar studies on the IRPs of 10 untypable
      strains revealed some of these to have different antigenic reactivities from
      those observed within the A and T biotypes.

PMID- 1373435
TI  - Cloning and structure of group C1 O antigen (rfb gene cluster) from Salmonella
      enterica serovar montevideo.
AB  - The Salmonella enterica group C1 O antigen structure has a Man-Man-Man-Man-GlcNAc
      backbone with a glucose branch, which differs from the S. enterica group B O
      antigen structure which has a Man-Rha-Gal backbone with abequose as side-chain.
      We have cloned the group C1 rfb (O antigen) gene cluster from serovar montevideo
      strain M40, using a low-copy-number cosmid vector. The restriction map of the
      group C1 (M40) rfb gene cluster was compared with that of group B strain LT2 by
      Southern hybridization and restriction enzyme analysis. The results indicate that
      the flanking genes are very similar in the two strains, but there is no
      detectable similarity in the rfb regions. We localized the mannose pathway genes
      rfbM and rfbK and one of the genes, rfbK, shows considerably similarity to cpsG
      of strain LT2, suggesting that part of the mannose pathway in the group C1 rfb
      cluster is derived from a gene of the M antigen (cps) cluster. The M antigen,
      which forms a capsule, is comprised of four sugars, including fucose. The
      biosynthetic pathway of GDP-fucose has steps in common with the GDP-mannose
      pathway, and the cps cluster has isogenes of rfbK and rfbM, presumably as part of
      a fucose pathway. We discuss the structure and possible evolution of the group C1
      rfb gene cluster.

PMID- 1373436
TI  - Expression of Bacillus amyloliquefaciens amylase and Vibrio alginolyticus
      protease A fusion genes.
AB  - Previously we reported [Deane, S. M., Maharaj, R., Robb, F. T. & Woods, D. R.
      (1987) Journal of General Microbiology 133, 2295-2302] that the production of a
      Vibrio alginolyticus SDS-resistant alkaline serine protease (Pro A) cloned in
      Escherichia coli was characterized by a 12 h delay between the synthesis of an
      inactive precursor and secretion of active Pro A. Replacement of the V.
      alginolyticus promoter region by the alpha-amylase promoter region from Bacillus
      amyloliquefaciens resulted in the simultaneous synthesis and secretion of Pro A
      in E. coli. The V. alginolyticus pro A gene cloned on a shuttle vector did not
      produce active Pro A in Bacillus subtilis. Although Pro A has a typical Gram
      positive signal sequence, it was not functional in B. subtilis. Replacement of
      the Pro A signal sequence with the alpha-amylase signal sequence resulted in the
      production of active Pro A in B. subtilis.

PMID- 1373437
TI  - Phylogenetic analysis of some Aerococcus-like organisms from urinary tract
      infections: description of Aerococcus urinae sp. nov.
AB  - Partial 16S ribosomal ribonucleic acid sequences of five Aerococcus-like
      organisms originally isolated from patients with urinary tract infections were
      determined using reverse transcriptase in order to clarify their taxonomic
      position. Analysis of the sequence data revealed that the clinical isolates
      represent a hitherto unknown line of descent within the genus Aerococcus. A new
      species, Aerococcus urinae, is proposed for these isolates. The type strain is
      NCFB 2893.

PMID- 1373438
TI  - Temporal relationships of hepatitis C virus RNA and antibody responses following
      experimental infection of chimpanzees.
AB  - Liver enzyme levels, viral RNA, and the immune response against both structural
      and nonstructural hepatitis C virus (HCV) proteins have been studied in
      experimentally infected chimpanzees in order to further understand the natural
      history of HCV infection. An ELISA for measuring both IgG and IgM responses to
      core (c22), 33c (NS3), and c100 (NS4) was employed. The IgG response rates were
      5/8 for core, and 8/8 for both 33c and c100. Utilizing this antigen combination,
      at least one antibody response is measureable at, or within 3 weeks of, the major
      ALT peak. Although no individual antibody response is universally associated with
      initial detection of seroconversion, the combination of all three recombinant
      proteins measures seroconversion an average of 54 days earlier than with c100
      alone, in 6/8 of the animals. IgM responses were measureable in 5/8 of the
      chimpanzees, were of shorter duration, and usually arose concomitantly with IgG
      responses. IgM appears to be a good indicator of primary infection since neither
      boosting nor recrudescence of disease during the chronic phase of disease
      elicited a secondary IgM response. Viral RNA can be measured 4-7 days (average =
      9 days) postinfection with the period preceding the ALT peak being characterized
      by several PCR positive segments interrupted by periods in which no viral RNA can
      be measured. Following the ALT peak, chronically infected animals with recurring
      ALT elevations are generally PCR positive with intercedent PCR negative periods.
      Those animals that appear to have biochemically resolved disease generally have
      PCR negative profiles, although they still may periodically exhibit PCR positive
      sera. This indicates that with the recent advent of new screening techniques, a
      more stringent definition of HCV resolution will be required.

PMID- 1373439
TI  - Transient and permanent effects of androgen during synapse elimination in the
      levator ani muscle of the rat.
AB  - Young male rats were castrated at 7 days of age, and treated with testosterone
      propionate daily from 7 to 34 days of age. At 13 months of age, motor axons and
      terminals innervating the levator ani (LA) muscle were stained with
      tetranitroblue tetrazolium (TNBT). The number of separate axons innervating
      individual muscle fibers was counted, and muscle fiber diameter was measured.
      Previous studies have shown that this androgen treatment increases muscle fiber
      diameter and delays synapse elimination, measured as (1) a greater percentage of
      muscle fibers innervated by multiple axons and (2) larger motor units. The
      present results indicate that the androgenic effect on synapse elimination is
      permanent, in that high levels of multiple innervation persisted for 12 months
      after the end of androgen treatment. In contrast, the effect on muscle fiber
      diameter was not maintained for this period. This dissociation of androgenic
      effects on the pattern of innervation from androgenic effects on muscle fiber
      diameter offers further evidence that the androgenic maintenance of multiple
      innervation is not dependent on muscle fiber size. In addition, circulating
      testosterone levels were measured at 50 and 60 days of age in animals similarly
      treated with androgen or oil from 7 to 34 days of age. By 60 days of age,
      testosterone levels in hormone-treated animals had dropped below detectability,
      comparable to levels in oil-treated controls. This provides additional evidence
      that androgen treatment during juvenile development can have permanent effects on
      the adult pattern of innervation in the LA muscle.

PMID- 1373440
TI  - Connections of the forewing tegulae in the locust flight system and their
      modification following partial deafferentation.
AB  - The flight motor pattern of the adult locust (Locusta migratoria L.) is able to
      recover from the loss of the hindwing tegulae. This recovery is due to a
      functional substitution of the hindwing tegulae by the forewing tegulae
      (Buschges, Ramirez, and Pearson, 1992). To assess changes in the pathways from
      the forewing tegulae in the flight system, we investigated the pathways of the
      forewing tegula in intact locusts and in animals 2 weeks after hindwing tegula
      removal. The following physiological alterations in these pathways were found to
      be associated with the recovery: (1) In the intact locusts, the connections of
      forewing tegula afferents to flight interneurons are variable but this
      variability did not occur in recovered animals, and (2) larger numbers of
      forewing tegula afferents connect to interneurons that excite elevator
      motoneurons (interneurons 566 and 567) and to an interneuron that inhibits
      depressor motoneurons (interneuron 511). The size of unitary excitatory
      postsynaptic potentials (EPSPs) evoked by signal forewing tegula afferents was
      found not to be altered in recovered animals. The changes in connectivity of
      forewing tegula afferents are correlated with morphological alterations in the
      structure of the terminal processes of the afferents and with sprouting of some
      branches of interneurons receiving input from these afferents.

PMID- 1373441
TI  - Tryptophan and biogenic amine metabolites in post-mortem human cisternal fluid:
      effects of post-mortem interval and agonal time.
AB  - Cisternal fluid (CF) tryptophan (TRP), 5-hydroxyindole-3-acetic acid (5-HIAA),
      3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxy-4
      hydroxyphenylglycol (MHPG) concentrations were measured from 40 adult cadavers.
      They were divided into 4 groups (n = 10 in each group), with samples taken 2, 4,
      10 and 24 h after death. The CF concentrations of TRP and all determined biogenic
      amine metabolites were distinctly higher than in lumbar CSF during life, and
      concentrations of 5-HIAA were also higher in post-mortem samples than in
      cisternal or ventricular CSF in living humans. The means of the samples of 5
      HIAA, DOPAC, HVA and MHPG were not statistically significantly different over
      time, but some trends were evident. TRP concentrations in CF increased linearly
      with time (from 4.6 to 23.6 mumol/l, P less than 0.001). CF DOPAC and HVA
      concentrations were dependent on agonal time and dopamine infusions. Our results
      imply that both ante-mortem and post-mortem conditions may influence monoamine
      metabolite and TRP concentrations in CF. These conditions should be accounted for
      in studies using post-mortem samples to study differences between patient groups
      in CNS neurochemistry.

PMID- 1373442
TI  - Effect of the expression of transforming growth factor-beta 2 in primary human
      glioblastomas on immunosuppression and loss of immune surveillance.
AB  - Glioblastomas are malignant brain tumors that are attended by an immunosuppressed
      state. The authors have studied the expression of transforming growth factor-beta
      2, which is known to have potent immunosuppressive and angiogenic properties.
      Transforming growth factor-beta 2 messenger ribonucleic acid and its protein
      product are both found to be greatly overexpressed in these tumors and are absent
      from normal brain tissue. The overexpression of this growth factor may contribute
      to the escape of neoplastic astrocytes from immune surveillance and, furthermore,
      to the immunosuppressed state that is characteristic of many of these patients.

PMID- 1373443
TI  - Endothelial cell chemotactic factor derived from human glioma cell lines.
AB  - The authors report a study of the human umbilical vein endothelial cell
      chemotactic factor derived from human malignant glioma cell lines. The
      endothelial cell chemotactic activity of serum-free conditioned medium from
      cultures of U-373MG, U-251MG, or U-105MG cell lines was measured using a 48-well
      microchemotaxis chamber. The best response was from U-373MG, which was selected
      for further study. Chemotactic activity was contained in materials unadsorbed and
      adsorbed to the heparin-affinity column. Because the higher activity was seen in
      the unadsorbed material, it was used for characterization and partial isolation.
      The chemotactic activity was decreased under the condition of tumor protein
      synthesis inhibition. Heating, exposure to acid, and trypsin digestion also
      decreased the activity. The factor was found to be a protein with a relative
      molecular weight of greater than 200 kD; it has no mitogenic activity for
      endothelial cells in vitro and, partially purified, it was not identical to any
      other known endothelial cell chemotactic or mitogenic factor. Fibronectin was not
      detected, and anti-fibronectin antibody failed to inhibit the activity of the
      factor. These results suggest that malignant glioma cells produce a yet unknown
      endothelial cell chemotactic factor.

PMID- 1373444
TI  - Interaction of acidic fibroblast growth factor and transforming growth factor
      beta in normal and transformed glia in vitro.
AB  - The mitogenic and morphological effects of acidic fibroblast growth factor (aFGF)
      and transforming growth factor-beta (TGF-beta) were assessed on cultured fetal
      rat astrocytes and C6 rat glioma cells in the presence and absence of serum.
      Astrocytes incubated with aFGF exhibited an increase in mitotic activity and
      characteristic morphological changes involving extensive process formation and
      rounding of cell bodies. Astrocytes incubated with TGF-beta underwent a slight
      decrease in mitotic activity and remained morphologically unchanged. Cells
      exposed to a combination of aFGF and TGF-beta demonstrated an attenuation of both
      the mitogenic and morphological changes observed in the presence of aFGF alone.
      The C6 glioma cells cultured in the presence of aFGF underwent a characteristic
      morphological change from a rounded piling cell mass to a more spindle-shaped
      bipolar cell layer, accompanied by an increase in mitotic activity. In contrast
      to the astrocyte cultures, increased growth and similar morphological effects
      were produced by TGF-beta. The combination of aFGF and TGF-beta did not result in
      attenuation of the mitogenic and morphological changes (as seen in astrocytic
      cells). These results suggest that, in normal fetal rat astrocytes, TGF-beta is
      capable of attenuating the mitogenic and morphological changes induced by aFGF in
      vitro. In the transformed C6 glioma cell line, aFGF and TGF-beta elicit similar
      mitogenic and morphological changes, without evidence of an antagonistic
      interaction as seen in normal astrocytes.

PMID- 1373445
TI  - Studies with compounds that compete with tryptophan binding to rat hepatic
      nuclei.
AB  - Tryptophan has been demonstrated to affect hepatic RNA and protein metabolism.
      Binding of tryptophan to nuclear envelope proteins has been demonstrated to be
      saturable, stereospecific, and of high affinity. The hepatic nuclear envelope
      tryptophan binding protein (glycoprotein) has been purified to apparent
      homogeneity using either concanavalin A-agarose or tryptophan-agarose. The
      receptor has an Mr of approximately 34,000, which is the same as that observed
      when [3H]tryptophan has been crosslinked to nuclear proteins. In this study, we
      investigated whether analogs, metabolites or related compounds of tryptophan as
      well as other amino acids may bind to rat hepatic nuclei using in vitro
      [3H]tryptophan binding assays. Our results indicate that compounds that compete
      with [3H]tryptophan binding to hepatic nuclei or nuclear envelopes contain the
      alpha-amino-propionic acid structure. Such compounds were 5-fluoro tryptophan, 7
      aza tryptophan, 5-hydroxy tryptophan, alanine, phenylalanine, tyrosine, cysteine
      and cystine. It was of interest that, whereas tryptophan-methyl ester and
      tryptophan-ethyl ester competed, alpha-methyl tryptophan, N-formyl tryptophan, N
      acetyl tryptophan, and N-methyl tryptophan did not compete with [3H]tryptophan
      binding to hepatic nuclei or nuclear envelopes. Nonetheless, only the in vivo
      administration of L-tryptophan was able to stimulate nucleocytoplasmic efflux of
      hepatic RNA and protein synthesis.

PMID- 1373446
TI  - The effect of food deprivation on brain and gastrointestinal tissue levels of
      tryptophan, serotonin, 5-hydroxyindoleacetic acid, and melatonin.
AB  - In order to investigate the effect of food deprivation on the levels of indoles
      in the brain and the gastrointestinal tissues, we have determined tissue levels
      of tryptophan (TRP), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and
      melatonin in the brain and the gastrointestinal tract (GIT) of mice on ad libitum
      diet as well as in mice deprived of food for 24 and 48 hr. The reduction of food
      intake 1) had no effect on TRP levels in the brain, but increased TRP
      concentrations in the stomach and the gut, especially in the colon; 2) decreased
      5-HT levels in the brain, but increased values in the stomach and the intestines;
      3) decreased 5-HIAA levels in the brain, but increased them in the stomach and
      the intestines; 4) did not change 5-HT conversion to 5-HIAA in the brain,
      stomach, and the jejunum, but increased the conversion in the ileum and colon
      and; 5) increased melatonin levels in all tissues investigated, particularly in
      the stomach and the brain. The changes of indole levels induced by food
      deprivation were compared to their known function in the brain and the individual
      segments of the GIT. A possible serotonin-melatonin antagonism in the brain and
      GIT function is considered.

PMID- 1373447
TI  - Elevated maternal serum alpha-fetoprotein levels and maternal risk factors. Their
      association with pregnancy complications.
AB  - Maternal serum alpha-fetoprotein (MS-AFP) screening programs identify a
      population of pregnant women with elevated MS-AFP values. When the levels are
      unassociated with a fetal anomaly, those women have a high incidence of pregnancy
      complications. Such patients were compared to a population with normal MS-AFP
      values to determine the incidence of historical risk factors and to ascertain if
      their presence affected the rate of pregnancy complications. A total of 358
      patients were followed prospectively, 23 with elevated MS-AFP levels and 335 with
      normal levels (control group). Historical risk factors were more frequent in the
      patients with elevated MS-AFP levels. There was a fourfold increase in the rate
      of pregnancy complications when a patient had both risk factors and elevated MS
      AFP levels as compared with elevated MS-AFP levels alone. In the control group,
      patients with known risk factors experienced twice the incidence of pregnancy
      complications as did patients with no risk factors. Using multiple logistic
      regression analysis, elevated MS-AFP levels were shown to be an independent
      variable in the risk assessment. The results of this study have wide application
      in the counseling and follow-up of patients identified by MS-AFP screening
      programs.

PMID- 1373448
TI  - Serum beta-human chorionic gonadotropin, estradiol and progesterone as early
      predictors of pathologic pregnancy.
AB  - We prospectively studied 110 asymptomatic female infertility patients with serial
      serum measures of beta-human chorionic gonadotropin (hCG), estradiol (E2) and
      progesterone (P) to determine their sensitivity, specificity, predictive value
      and test efficiency, alone or in combination, for the prediction of pathologic
      gestations prior to five weeks after ovulation. Circulating levels of serum beta
      hCG, E2 and P were measured at 48- or 72-hour intervals. Seventy-four patients
      (67%) had viable pregnancies, for which the abnormal changes in steroid levels
      were defined as: a beta-hCG rise of less than 66% in 48 hours or less than 120%
      in 72 hours, an E2 decline of greater than 15% in 48 hours or greater than 20% in
      72 hours, or a P decline of greater than 25% in 48 hours or greater than 33% in
      72 hours. Thirty-six women (33%) had pathologic pregnancies, which included
      ectopic pregnancies (8), spontaneous or missed abortions (7), blighted ova
      (anembryonic gestation, 20) and hydatidiform mole (1). For the detection of
      pathologic pregnancies in this asymptomatic infertility population, the
      sensitivity of beta-hCG, E2 and P, singly or in combination, ranged from 34% to
      78%, and the test efficiency ranged from 68% to 88%. Beta-hCG alone provided the
      highest sensitivity (78%) and test efficiency (88%). When compared to measuring
      serial beta-hCG alone, serum E2 or P did not enhance the test efficiency and
      lowered the sensitivity for the detection of pathologic pregnancies in an
      asymptomatic infertility population.

PMID- 1373449
TI  - The effects of glycol methacrylate as a dehydrating agent on the dimensional
      changes of liver tissue.
AB  - The dimensional changes of liver sections during the course of processing with
      glycol methacrylate (GMA) or with ethanol are described. Tissue processing with
      ethanol served as a control. During prolonged processing steps (24 h each),
      linear shrinkage of tissue specimens dehydrated with GMA at room temperature was
      13.2%. Subsequent infiltration with GMA resulted in trivial swelling, and
      polymerization in slight shrinkage (2.3%). In comparison, processing with cold
      GMA resulted in shrinkage during dehydration (about 10.8%), a slight swelling in
      pure GMA, followed by shrinkage during polymerization (2.2%). Short routine
      processing schedules resulted in similar shrinkage/swelling patterns, although
      precise values differed slightly. In all experiments, ethanolic dehydration
      resulted in smaller dimensional tissue changes than did GMA dehydration. The
      dimensional changes of tissue sections during stretching on water, mounting and
      drying compensated for the major part of the shrinkage manifested during
      processing.

PMID- 1373451
TI  - [Cancer of the penis and its treatment].
AB  - It had been believed that carcinoma of the penis was rather rare in the developed
      countries comparing with that in the under-developing countries, however, the
      recent epidemiological studies failed to reveal any clear difference of the
      incidence of carcinoma of the penis all over the world. In these days so called
      successful treatment is coming to be evaluated by the quality of life (QOL) after
      surgical or nonsurgical treatment (especially sexual function tended to be
      considered very important factors altering QOL). I want to emphasize the
      following issues in this report. 1. Erythroplasia of Queyrat and Bowen's disease
      are carcinoma in situ and should be dealt as carcinoma of the penis. 2. relation
      of human papilloma virus and carcinoma of penis. 3. usefulness of TNM
      classification over Jackson's classification. 4. SCC antigen is a reliable tumor
      marker of carcinoma of the penis? 5. effectiveness of chemotherapy based on BLM
      combined with radiation therapy for carcinoma of the penis. 6. usefulness of Mohs
      microscopically controlled surgery and modified groin dissection. It is generally
      accepted that since carcinoma of the penis is a rare disease and for one
      institution up to 50 cases can be experienced during 20 years in Japan, there
      exist no integrated study involving a large number of institutions. I really wish
      a certain form of group study to be completed and the results from this study
      utilized to overcome the present problems for the treatment of carcinoma of the
      penis.

PMID- 1373450
TI  - Distribution of the neuropeptide galanin in the cat heart and coexistence with
      vasoactive intestinal peptide, substance P and neuropeptide Y.
AB  - The neuropeptide galanin (GAL) has been detected in the peripheral and central
      nervous systems. However, little is known about its distribution and localization
      in heart, and the possible coexistence of GAL with other neuropeptides in the
      heart is not established. The present immunocytochemical study describes the
      distribution of GAL in nerves of the feline heart and its colocalization with
      vasoactive intestinal peptide (VIP), substance P (SP), and neuropeptide Y (NPY).
      GAL-like immunoreactivity was widely distributed in the atrial and ventricular
      myocardium and around coronary arteries. Colocalization of GAL with VIP, SP and
      NPY was observed in many nerve fibers. Further, GAL and NPY were colocalized in
      nerve cell bodies of intracardiac ganglia. Since these neuropeptides have been
      found to be associated with sensory and autonomic innervation in the heart, the
      present findings provide evidence that GAL is shared by functionally different
      neuronal populations in the heart and that GAL may participate in controlling
      cardiac function by combined action with other neuropeptides.

PMID- 1373452
TI  - [Influential factors on recurrence of renal cell carcinoma].
AB  - In order to clarify factors affecting recurrence, we reviewed 115 renal cell
      carcinoma patients without distant metastasis at diagnosis (Mo) treated from
      January 1975 to March 1990 at Sapporo Medical College Hospital. Of these 115
      patients, recurrence (metastasis) was found in 23 (20.0%). The non-recurrence
      rate was 70.6% after the 5-year and 56.5% after the 10-year follow up. In 22 out
      of 23 patients, recurrence appeared within 3 years following surgery.
      Multivariate analysis by Cox's proportional hazard model revealed that lymph node
      metastasis was the most significant factor for recurrence in the 115 patients
      followed by stage of the primary tumor and pre-operative acute phase reactant
      (fever, ESR and alpha 2-globulin) in this order. When the analysis was performed
      in the 88 patients who was in less advanced stage (pN0pV0-1a), pre-operative
      acute phase reactant (fever, ESR and alpha 2-globulin) was identified as the only
      significant factor affecting recurrence. This result suggests that pre-operative
      acute phase reactant is the most important risk factor for recurrence in this
      group of patients.

PMID- 1373453
TI  - [Chromosomal abnormalities in carcinoma and hyperplasia of the prostate].
AB  - Epithelioid cells that had grown in short-term cultures derived from 10 cases of
      adenocarcinoma (PCa) and 10 cases of hyperplasia (BPH) of the prostate were
      karyotyped by the G-banding method for the pathogenesis of these disease. PCa
      specimens included 4 well, 2 moderately, and 4 poorly differentiated types, and
      were obtained by perineal needle biopsy from 4 patients in stage B and 6 patients
      in stage D2. Cells liberated from metastatic lymph node lesions of 2 patients
      with poorly differentiated PCa were also analyzed directly without cultivation in
      vitro. All BPH specimens were obtained by prostatectomy, and cells that had grown
      in epithelioid pattern in short-term cultures were analyzed. In PCa, hyperploidy
      was seen in all but 2 cases. Structure analysis disclosed abnormality of
      chromosome 16 in 4 PCa, deletion of Y in 3 PCa, abnormality of chromosomes 7, 14,
      15, 18, and 19 in 2 PCa, and abnormality of chromosomes 3, 4, 17, and 21 in 1
      PCa. Multiple markers were observed in 1 patient, and hyperploidy in another
      patient with metastatic lymph nodes. All but 2 cases of BPH were diploid. Normal
      male karyotypes were seen in 6 BPH. Trisomy of chromosomes 7 and 16 were observed
      in 2 BPH. Of 4 patients with stage B PCa, 3 who have been alive for 3 years to
      date had multiple abnormalities, whereas 1 patient who died 2 years after
      diagnosis had few abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373455
TI  - [Quantitative analyses of alpha-adrenoceptors in human prostatic capsule, adenoma
      and urethra--a comparison between normal prostate and hypertrophied prostate].
AB  - The adrenergic alpha-1 and -2 receptors in the three layers of the prostate
      (capsule, adenoma and urethra) were measured in humans with or without benign
      prostatic hypertrophy to examine the differences between the hypertrophied and
      non-hypertrophied (normal) prostate. Both alpha-1 and -2 receptors were found to
      exist in similar amounts in prostatic adenoma of both hypertrophied and normal
      prostate groups. In the prostatic capsule and urethra of both groups alpha-1
      receptors were more abundant than alpha-2 receptors. Both alpha-1 and -2
      receptors in all three prostatic layers were found to be increased significantly
      in hypertrophied group compared to normal group. Further more the increases in
      alpha-1 and -2 receptors of hypertrophied group were most remarkable in prostatic
      adenoma. These results seems to demonstrate that not only alpha-1 but also alpha
      2 receptors play some important roles in benign prostatic hypertrophy.

PMID- 1373454
TI  - [Analysis of tumor volume in latent prostatic carcinoma].
AB  - An assessment has been made of the histopathological characteristics of latent
      prostatic carcinoma and the tumor volume in 500 male Japanese patients who
      underwent dissection at The Jikei University since 1983. A microscopic
      observation was made of the prostatic glands extirpated totally at the necropsy,
      fixed with formalin and prepared as a step-section in a thickness of 3 mm. In the
      cases of latent carcinoma, after photographing the lesion in the same
      magnification and measuring the area of the carcinoma lesion with a digitizer,
      the volume was calculated by multiplying the thickness of 3 mm, and carcinoma
      volume was determined by integrating the value of each slice and adjusted by a
      conversion formula. The incidence of latent carcinoma was 104 cases out of 500
      (22%). The incidence increased as the age layer becomes higher, and latent
      carcinoma was observed in 44% of the patients aged 80 and above. Complication of
      latent carcinoma with prostatic hyperplasia was presumed to be an independent
      phenomenon in so far as it is seen from the statistical aspect. The patients were
      classified histopathologically into well-differentiated type (64%), mixed type
      (27%) and poorly-differentiated type (9%), showing high incidence in the low-aged
      layer of well-differentiated lesions and in the high-aged layer of mixed type
      lesions and in the high-aged layer of mixed type lesions. The average tumor
      volume of latent carcinoma was so small as 231 mm3, but many of the lesions in
      the cases of well-differentiated type were small, being on average 103.9 mm3, but
      many of the lesions in the cases of poorly-differentiated type were large, being
      on average 642.2 mm3. Statistically, with a tumor size of 200 mm3 as the
      boundary, a difference was observed in the distribution of histological
      constitution between the group with smaller lesions and the group with larger
      lesions. As an application of this result to the clinical carcinoma of stage A,
      the value of volume of 200 mm3 was considered to be important as a diagnostic
      criterion in deciding the necessity of treatment.

PMID- 1373457
TI  - [Relationship between bladder trigone and bladder neck induced by traction of an
      indwelling balloon catheter with a spring balance and parameters of
      cystometrogram].
AB  - Sensation of the bladder trigone and bladder neck induced by traction of an
      indwelling balloon catheter with a spring balance and cystometry was evaluated in
      393 males and 106 females. Male patients with an average age of 56.9 +/- 15.9
      (mean +/- standard deviation) years old (range 17 to 88 years) were divided into
      7 groups as follows: 19 patients without any micturitional disturbance, uregency
      and chronic prostatitis (11 patients), benign prostate hypertrophy (BPH) (131
      patients), cervical or thoracic cord compression disorders (67 patients), lumbar
      vertebral disorders (114 patients), other peripheral nerve disorders associated
      with diabetes mellitus, post operative status of rectum cancer and others (27
      patients) and brain diseases (24 patients). Female patients with an average age
      of 55.2 +/- 15.5 years old (range 17 to 88 years) were divided into 6 groups as
      follows: 24 patients without any neurological problems, urgency (7 patients),
      cervical or thoracic cord compression disorders (11 patients), lumbar vertebral
      disorders (37 patients), other peripheral nerve disorders (18 patients) and brain
      diseases (9 patients). The observed sensation, first desire to void (FDV) and
      maximum cystometric capacity (MCC) were evaluated statistically in relation to
      clinical factors (e.g. disease group, generation and patterns of cystometrogram).
      The correlation between the sensation and FDV or MCC in these patients were
      assessed by linear regression analysis. Sensation of normal males was 334.2 +/-
      159.7 g on the average and correlated well with FDV (r = 0.88, y = 375x - 189.4).
      Sensation of normal females was 373.3 +/- 199.5 g on the average. However, there
      was no correlation (r = 0.35) between sensation and FDV in females. In males, the
      means of sensation obtained in patients with other peripheral nerve disorders
      (557.3 +/- 314.5 g) was significantly larger than the means of normal subjects (p
      less than 0.001), and patients with uregency and chronic prostatitis (236.4 +/-
      148.3 g, p less than 0.01), BPH (424.1 +/- 215.6 g, p less than 0.001), cervical
      or thoracic cord compression disorders (349.0 +/- 229.5 g p less than 0.001),
      lumbar vertebral disorders (349.7 +/- 201.7 g, p less than 0.001) or brain
      diseases (490.6 +/- 305.0 g, p less than 0.05). Furthermore, the differences in
      the means of sensation between BPH and lumbar vertebral disorders (p less than
      0.05) or brain diseases (p less than 0.05) were statistically
      significant.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1373456
TI  - [Comparison of selective alpha-1 blockades for alpha-receptors in human
      hypertrophied prostatic adenomas].
AB  - The adrenergic alpha-1 and -2 adrenoceptors in six human hypertrophied prostatic
      adenomas were measured in the saturation experiment using 3H-prazosin and 3H
      yohimbine. Not only alpha-1 adrenoceptons, but also alpha-2 adrenoceptors were
      found to exist in large amounts in prostatic adenomas. In the inhibition
      experiment selective alpha-1 antagonists inhibited the 3H-prozosin or 3H
      yohimbine bindings to adenomas. The potency of alpha-1 antagonists in the order
      prazosin greater than bunazosin greater than alfuzosin greater than urapidil
      greater than terazosin and that of alpha-2 antagonists is urapidil greater than
      alfuzosin greater than terazosin greater than bunazosin greater than prazosin.
      These data suggest that urapidil, alfuzosin and terazosin may affect the human
      hypertrophied prostatic adenoma like phenoxybenzamine, nonselective alpha-1
      antagonist, which was used for benign prostatic hypertrophy.

PMID- 1373458
TI  - [Clinical experience of local thermotherapy in the treatment of benign prostatic
      hyperplasia].
AB  - Thirty-five patients with benign prostatic hyperplasia (age range: 45-88 years;
      average: 67.5 years) underwent local thermotherapy with prostathermer. Clinical
      therapeutic effect was evaluated in 30 of the 35 patients: 2 patients
      interrupting from therapy and 3 receiving pretherapeutic indwelling catheters
      were not included. A total of 6 treatments (2 per week) were performed, each
      lasting for 60 minutes. As for subjective improvement, improvement of nocturia
      was noted in 70.0% of all patients and sense of residual urine in 70.7%. Post
      therapeutic nocturnal and daytime decreases in urination frequency were
      statistically significant (p less than 0.01). Objective improvement in residual
      urine volume occurred in 19 of the 30 cases, and elevation in uroflowmetric
      maximal flow rate following therapy was statistically significant (p less than
      0.05). Among complications ascribable to catheter insertion were urethral
      bleeding (3 cases), epididymitis (1 case) and pyuria (1 case). Therapeutic result
      based primarily on subjective symptoms and partly on objective findings was
      fairly good in 17 cases (about 57%), and slightly good in 25 cases (about 83%).
      In conclusion, this therapy seems to be useful in the treatment of benign
      prostatic hyperplasia.

PMID- 1373459
TI  - T-cell receptor gamma/delta expressing acute leukemia emerging from sideroblastic
      anemia: morphological, immunological, and cytogenetic features.
AB  - Striking numerical and structural chromosome abnormalities (-Y, +8, i(7q), del
      (10)(q24), and del (11)(q21)) were detected by cytogenetic analysis in a
      patient's bone marrow with morphological features of both acute lymphoblastic
      leukemia and myelodysplastic disorder. Surface marker analysis characterized
      blast cells to be CD2+ CD7+ CD3+ CD4- CD8- expressing gamma/delta-T-cell receptor
      antigen and coexpressing CD11b and CD16. Exhibiting an identical phenotype as the
      leukemic cells, a prominent gamma/delta-TCR+ lymphocyte population was found in
      the bone marrow as well as in the peripheral blood. Cells of the latter
      compartment coexpressed CD56 and HLA-DR antigens and exhibited nonspecific
      cytotoxic activity. In the bone marrow cells NSCA could be induced after
      stimulation with interleukin 2 in vitro. Morphological, immunological, and
      cytogenetic findings suggest that gamma/delta-T-ALL emerged from a
      myelodysplastic disorder after sequential steps of malignant transformation.
      Leukemic cells with "mixed lineage" character may provide evidence for a common
      progenitor cell in the bone marrow. Assuming that the leukemic cells represent
      the malignant counterpart of normal CD3+ gamma/delta-TCR+ cells the results may
      contribute to our understanding of the origin and differentiation as well as the
      possible steps of malignant transformation of a gamma/delta-TCR+ lymphocyte
      population.

PMID- 1373460
TI  - Effect of combination chemotherapy with cefoperazone on non-Hodgkin's lymphoma.

PMID- 1373461
TI  - Angiogenesis and regressing cutaneous malignant melanoma.

PMID- 1373462
TI  - Didanosine and amylase monitoring.

PMID- 1373463
TI  - Tenascin expression in human chronic liver disease and in hepatocellular
      carcinoma.
AB  - Tenascin is an oligomeric glycoprotein of the extracellular matrix synthesized
      during embryonic development. It is prominently expressed in a variety of tumors.
      The role of tenascin in liver tissue is, however, unknown. We used
      immunocytochemistry to define the localization of tenascin and compare this with
      the localization of non-collagenous proteins, such as laminin and fibronectin, in
      normal human liver and pathological liver from patients with chronic hepatitis,
      liver cirrhosis and hepatocellular carcinoma. In normal liver, tenascin
      expression was localized along the sinusoidal and vascular wall. In fibrotic
      liver, tenascin was also observed in the region between the hepatic parenchyma
      and the fibrosing portal tracts, especially in areas of piecemeal necrosis in
      chronic hepatitis. Immuno-EM study of liver tissue in chronic hepatitis strongly
      suggested the synthesis and secretion of tenascin by fat-storing cells into the
      space of Disse. In hepatocellular carcinoma, tenascin was expressed in both the
      capsule and lobular septa, but not in the sinusoidal walls of the tumors. These
      results led us to postulate a close relationship between the occurrence of this
      protein and disease processes such as fibrosis and cancer invasion.

PMID- 1373464
TI  - An investigation of the origins of contrast in NMR spin echo images of plant
      tissue.
AB  - The effects that the spatial distribution of water protons and their transverse
      relaxation times have on the image contrast of spin echo images of courgette was
      investigated. The T2-weighted image of courgette contains the most anatomical
      information. The image contrast was explained using a phenomenological theory
      based on the Bloch equations, which gave an insight into the morphology and
      microdynamics of water in the plant tissue. The perceived contrast in the spin
      echo images of courgette, glucose and Sephadex bead solutions can be dramatically
      altered by keeping all the imaging acquisition parameters constant, such as the
      recycle and echo time, but reducing the interpulse spacing by introducing a CPMG
      train of 180 degrees pulses into the middle of the sequence. These changes were
      interpreted by considering the microenvironment of the water. This work
      demonstrates that the origin of image contrast in T2-weighted images of plant
      tissue can be understood using the water proton transverse relaxation theory
      developed by Hills et al.

PMID- 1373465
TI  - Antigenic regions of tumor necrosis factor alpha and their topographic
      relationships with structural/functional domains.
AB  - The immunogenic regions of human Tumor Necrosis Factor alpha (huTNF) have been
      mapped by studying the interaction between various mouse anti-huTNF sera and
      synthetic huTNF fragments, spanning the entire sequence of huTNF. Three main
      immunogenic regions were identified within residues 1-23, 95-116 and 137-157 of
      huTNF and two other less immunogenic regions within residues 117-136 and 37-55.
      The same huTNF regions were found to contain antigenic sites by binding studies
      with cognate anti-peptide sera. Competitive binding experiments with shorter
      synthetic subfragments provided evidence for the location of strong antigenic
      sites within residues 1-10, 17-23, 104-112 and 137-143. In particular the
      immunodominant site was found to be located within residues 104-112. huTNF
      regions corresponding to residues 24-36, 56-75, 76-94, and 147-157 resulted to be
      not or poorly antigenic. However, treatment of huTNF with Triton X-100 under
      conditions that partially dissociate the oligomeric quaternary structure resulted
      in the exposition of sites recognized by sera against peptides huTNF [56-75] and
      huTNF [76-94], suggesting that antigenic sites not accessible in the oligomeric
      huTNF are exposed in the dissociated form. The principal antigenic sites in the
      oligomeric molecule are localized in the flexible N-terminal part and in
      hydrophilic segments located in the "middle/top" region of the molecule, opposite
      to the C-terminus. Protein segments of the "bottom" region, close to the C
      terminus, were poorly immunoreactive. Neutralization assays of TNF cytolytic
      activity on L-M cells showed that binding of antibodies to epitopes located in
      the "middle/top" regions of huTNF does not affect its cytolytic activity,
      supporting the hypothesis of a receptor binding site location at the "bottom" of
      TNF trimer.

PMID- 1373466
TI  - Localization of the conformational alteration of MHC molecules induced by the
      association of mouse class I heavy chain with a xenogeneic beta 2-microglobulin.
AB  - Changes in the antigenicity of major histocompatibility complex (MHC) class I
      molecules resulting from the association of bovine beta 2-microglobulin (beta 2
      m) with mouse class I heavy chains were investigated. Mice (H-2b) were immunized
      with syngeneic Concanavalin A (Con A) blasts induced in the presence of fetal
      calf serum (FCS) in conditions allowing exchange between mouse and bovine beta 2
      microglobulin (beta 2-m). Spleen cells from hyperimmunized mice were fused with
      myeloma cells and two monoclonal antibodies which required for their reactivity
      the presence of FCS have been further studied. One of them (CAB 297) recognized a
      determinant of bovine beta 2-m which is present on free molecules in solution as
      well as when they are associated with either mouse or bovine class I heavy
      chains. In contrast, the second monoclonal antibody (CBB 70) did not react with
      free bovine beta 2-m molecules, nor with beta 2-m associated with bovine class I
      heavy chains. It did react with cells of some H-2 haplotypes (b, f, p and r) but
      only when their class I heavy chains are associated with bovine or with human
      beta 2-m. Therefore, expression of the CBB 70 defined antigenic determinant
      requires both xenogeneic beta 2-m and class I heavy chain of a given H-2
      molecule. In order to precisely localize the antigenic determinant defined by
      this monoclonal antibody and therefore the region altered by the association of
      class I heavy chain with xenogeneic beta 2-m, we made use of exon shuffled class
      I molecules. The results indicate that changes induced by the association of
      bovine beta 2-m with H-2 class I heavy chain affect the conformation of the alpha
      2 domain. These studies illustrate that MHC class I molecules exhibit a
      considerable conformational flexibility which could influence their ability to
      bind and present various peptides to the T-cell receptor.

PMID- 1373467
TI  - T helper cell epitopes of the human immunodeficiency virus (HIV-1) nef protein in
      rats and chimpanzees.
AB  - T helper cell antigenic and immunogenic determinants of the nef protein were
      investigated in the rat and chimpanzee models using recombinant nef protein and
      five synthetic peptides selected according to their amphipathic and alpha
      helicity properties. The nef protein was shown to be immunogenic with both
      Freund's or aluminium hydroxide adjuvants. After immunization with the nef
      protein the 45-69 peptide was the most antigenic in rat and monkey models. In
      contrast, the 98-112 peptide, that required a carrier protein to induce in vitro
      rat T cell recall proliferation, was able to restimulate monkey T cells in the
      absence of a carrier. The amino acid sequence carrying the antigenic activity of
      the 45-69 peptide was further investigated by synthesizing short peptides
      overlapping this region. The antigenic sequence was precisely located in the
      middle of the peptide (region 50-59). This sequence was antigenic only when N
      alpha-acetylated. Circular dichroism analysis of the 45-69 peptide and the in
      vitro activity of the N-terminus group indicate in this case the involvement of
      the alpha-helical propensity for antigen presentation. However, the shorter
      sequence 50-64, able to induce a T cell reactivity, was determined as a beta
      pleated sheet structure in aqueous solution. The 45-69 peptide was not only
      antigenic but also immunogenic and behaved in vivo as a functional T helper cell
      epitope. Indeed, the priming with the peptide or the transfer of peptide specific
      T cells to a naive recipient, followed by immunization with the nef protein,
      enhanced the subsequent antibody response to the nef protein. Together, these
      data indicate that the 45-69 peptide appears as a candidate for the in vivo
      elicitation of T cell immunity to the HIV-1 nef regulatory protein.

PMID- 1373468
TI  - A common epitope of beta-lactoglobulin and serum retinol-binding proteins:
      elucidation of its core sequence using synthetic peptides.
AB  - One of the monoclonal antibodies raised against bovine beta-lactoglobulin reacted
      with human serum retinol binding protein. The finding that this monoclonal
      antibody also reacted with the serum retinol binding proteins isolated from other
      animals, suggested that this epitopic conformation is conserved among these
      proteins. Using ELISA and various synthetic peptides of defined sequence, we show
      in this paper that the epitope defined by this monoclonal antibody comprises of
      the highly conserved core sequence of DTDY present in beta-lactoglobulin and
      retinol binding proteins.

PMID- 1373470
TI  - [Familial manifestation of idiopathic atrial flutter].
AB  - We describe, to the best of our knowledge for the first time, the occurrence of
      idiopathic atrial flutter (AF) in two male children of a family. The two brothers
      are the third and sixth of seven children, and the only males. The parents do not
      suffer from any heart disease. The first sister died in Turkey at the age of
      twenty days. The parents do not know the cause of death. The fourth sister died
      at de age of five years, also in Turkey, probably because of meningitis.
      Electrocardiograms of the parents and the other three sisters are normal. Besides
      the unique familial occurrence, the AF themselves offer some unusual features. In
      the first patient, the AF could not be converted to sinus rhythm. In the second
      patient, the AF occurred paroxysmally, and in addition to the AF, the
      electrocardiogram tracings revealed paroxysmal atrial tachycardia.

PMID- 1373469
TI  - Characterisation of the anti-A antibody response following an ABO incompatible
      (A2 to O) kidney transplantation.
AB  - Anti-A,B antibodies produced in a blood group OLe(a-b-) recipient receiving a
      kidney graft from a blood group A2Le(a-b+) donor have been analysed for their
      ability to bind to different glycosphingolipid antigens. Solid-phase RIA using
      pure glycosphingolipid antigens and a chromatogram binding assay using total
      nonacid glycosphingolipid fractions from erythrocytes of different human blood
      group phenotypes together with pure glycolipid antigens were used as assay
      systems. Serum antibodies were shown to bind equally well to A (types 1, 2, 3 and
      4) and B (types 1 and 2) antigenic structures but no binding to H antigens (types
      1, 2 and 4) was detected. After adsorption of serum antibodies on A1 Le(a-b+)
      erythrocytes there was a residual anti-A antibody activity which could not be
      adsorbed by synthetic A-trisaccharides coupled to crystalline silica (Synsorb-A).
      These residual antibodies, which are not present in a pretransplant serum sample,
      had a specificity for the A antigen with type 1 core saccharide chain and the
      binding epitope obviously included both the N-acetylgalactosamine and the N
      acetylglucosamine. The fucose residue was apparently not obligate for binding.
      The conformation of the sugar units involved in the binding epitope was
      determined.

PMID- 1373471
TI  - Adhesion in skeletal muscle during regeneration.
AB  - Adhesion molecules were studied in regenerating skeletal muscle
      immunohistochemically and ultrastructurally after a standardized trauma. In
      normal muscle, extracellular matrix (ECM) protein tenascin was restricted to
      myotendinous junctions (MTJ), while the integrin beta 1-subunit was present also
      on the sarcolemma. After injury, tenascin increased on the outer surface of
      regenerating myofibers, where cellular fibronectin also accumulated. Later,
      tenascin concentrated at the tips of regenerating myofibers, where new MTJs were
      formed. The beta 1-subunit disappeared on necrotized myofibers and reappeared on
      regenerating fibers in a thicker layer. The regenerating myofibers were invested
      by a basal lamina, except for the growth cones at the distal ends, which were
      laminin-negative until the formation of MTJs occurred. These results indicate
      that regenerating muscle cells are attached to the ECM in a way that allows both
      growth of the muscle cells across the scar and their use before the regeneration
      is completed.

PMID- 1373472
TI  - Variable and conserved structural elements of trypanosome variant surface
      glycoproteins.
AB  - The characterization of B cell epitopes on the trypanosome variant surface
      glycoprotein (VSG) rests on elucidation of variant specific amino acid sequences
      that may be exposed or buried as a result of the natural conformation of these
      molecules in the surface coat. Despite the fact that different VSGs have
      heterogeneous primary sequences and unique antigenic characteristics, recent high
      resolution X-ray crystallographic analyses of VSGs have revealed a conserved 3
      dimensional structure common to these surface proteins [19]. We took advantage of
      this conserved structural conformation to help predict which variant subregions
      of VSG molecules may contain exposed or buried variant specific B cell epitopes.
      Using Staden data tables, we aligned the deduced amino acid sequence of
      Trypanosoma brucei rhodesiense LouTat 1 VSG, a molecule that has been
      characterized immunologically in this laboratory, with 12 other complete VSG
      sequences including the T. b. brucei MiTat 1.2 VSG that has been characterized in
      crystallographic studies. Results of this analysis predict that there are eight
      defined clusters of variant amino acids which may contribute to exposed B cell
      epitopes, and ten defined clusters of variant amino acids which may contribute to
      buried B cell epitopes, on all VSG molecules. Interestingly, this analysis also
      revealed a VSG consensus sequence in which certain conserved motifs are present
      in all VSGs. The shared elements of VSG sequences corresponded to known secondary
      structures present in MiTat 1.2, and included groups of conserved amino acids
      responsible for turns in subregions of the protein, for structural positioning of
      the variable residues on the exposed surface, and for the dimerization of VSG
      monomers. Overall, these observations may aid in the targeting and mapping of
      exposed and buried VSG specific B cell epitopes, and also may offer clues as to
      elements of the primary sequence that are important for the conserved 3
      dimensional structure of antigenically distinct VSG molecules.

PMID- 1373473
TI  - Sequence variation in the tripeptide repeats and T cell epitopes in P190 (MSA-1)
      of Plasmodium falciparum from field isolates.
AB  - The N-terminal part of p190, the precursor to the major merozoite surface
      antigens of Plasmodium falciparum, contains the T and B cell epitopes and
      tripeptide repeats. The p190 gene exhibits allelic dimorphism, but the tripeptide
      repeat-encoding region is the only exception to the dimorphic variations of the
      gene. To date, sequences available to document variations in the epitopes are
      very limited. Thus, in this study, the extent of the variation in these regions
      was analyzed using the polymerase chain reaction to amplify the DNA fragment
      encompassing these regions, followed by sequencing. Twenty-five gene clones were
      obtained from 19 isolates from the Mae Sod district in Thailand and their
      sequences were compared with those reported elsewhere. Results reveal 3 sequence
      types in the tripeptide-encoding region, and each contains a novel repetitive
      consensus nucleotide sequence. On the other hand, almost all nucleotide
      substitutions in block III are dimorphic. Identification of linkages of the
      dimorphic substitutions has led us to postulate 6 potential crossover sites,
      where intragenic recombinations of p190 alleles could occur. Sequences of T and B
      cell epitopes are highly conserved among these wild isolates and those from
      geographically diverse culture-adapted parasites.

PMID- 1373474
TI  - [Is sympathetic reflex dystrophy really "defined as an entirely neurologic
      disorder"? Critical remarks on the contribution by H. Blumberg, H.-J. Griesser
      and M. Hornyak. Neurologic aspects of clinical manifestations, pathophysiology
      and therapy of sympathetic reflex dystrophy (causalgia, Sudeck's disease)].

PMID- 1373475
TI  - Effect on hemoglobin F synthesis by erythropoietin in patients with anemia of end
      stage renal disease maintained by chronic hemodialysis.

PMID- 1373476
TI  - Treatment of gross hematuria in autosomal dominant polycystic kidney disease with
      aprotinin and desmopressin acetate.

PMID- 1373477
TI  - Colocalization of peptide and glucocorticoid receptor immunoreactivities in rat
      central amygdaloid nucleus.
AB  - The central amygdaloid nucleus (ACe) is part of the amygdaloid complex that
      participates in adrenocorticotrophin secretion, stress-related reactions and
      behavioral functions. The ACe contains numerous glucocorticoid receptor (GR)
      immunoreactive (IR) neurons, and in addition it has been shown to contain several
      neuropeptide-IR somata and nerve terminals. In order to study the relationship
      between the GR- and neuropeptide-IR structures we mapped the distribution of GR
      like immunoreactivity (LI) in amygdaloid complex and colocalized the neuropeptide
      and GR-LIs in the ACe. In the amygdaloid complex the central, medial and
      cortical nuclei contained a high number of GR-IR neurons, whereas a moderate
      number of GR-IR neurons were observed in the basolateral and basomedial nuclei.
      Only a few GR-IR neurons were seen in the lateral nucleus. In the ACe, the
      majority of corticotrophin-releasing factor (CRF)-, met-enkephalin (met-ENK)-,
      neurotensin (NT)- and somatostatin (SOM)-IR neurons contained also GR-IR. About
      half of the substance P (SP)-IR neurons were seen to contain GR-IR, whereas only
      some of the few vasoactive intestinal polypeptide and cholecystokinin-IR neurons
      showed GR-LI. Nerve terminals containing calcitonin gene-related peptide and the
      above mentioned peptides were seen in close contact with the GR-IR neurons. These
      results suggest that the glucocorticoids may modulate directly the
      neurotransmitter synthesis of the CRF-, met-ENK, NT-, SOM- and SP-IR cells in the
      ACe.